review_id
stringlengths 8
8
| pmid
list | title
list | abstract
list | target
stringlengths 56
2.23k
|
|---|---|---|---|---|
CD003664
|
[
"12642834",
"10981524",
"9279143",
"7562275",
"10452771",
"9062633",
"1447641",
"1586005",
"21055664",
"1776437",
"7971447",
"11338290",
"18158176",
"11736743",
"21481024",
"8888916",
"11114686"
] |
[
"The effect of hydrolyzed cow's milk formula for allergy prevention in the first year of life: the German Infant Nutritional Intervention Study, a randomized double-blind trial.",
"Comparison of a partially hydrolyzed infant formula with two extensively hydrolyzed formulas for allergy prevention: a prospective, randomized study.",
"Extensively and partially hydrolysed infant formulas for allergy prophylaxis.",
"Efficacy and safety of hydrolyzed cow milk and amino acid-derived formulas in infants with cow milk allergy.",
"Supplementary feeding in maternity hospitals and the risk of cow's milk allergy: A prospective study of 6209 infants.",
"Immunogenicity and antigenicity of a partially hydrolyzed cow's milk infant formula.",
"Long-term prevention of allergic diseases by using protein hydrolysate formula in at-risk infants.",
"Effect of a whey hydrolysate prophylaxis of atopic disease.",
"Oral immunotherapy for cow's milk allergy with a weekly up-dosing regimen: a randomized single-blind controlled study.",
"The effect of hypoallergenic formula on the occurrence of allergic diseases in high risk infants.",
"[The prevention of allergic diseases with a hypoallergenic formula: a follow-up at 24 months. The preliminary results].",
"Prospective, controlled, multi-center study on the effect of an amino-acid-based formula in infants with cow's milk allergy/intolerance and atopic dermatitis.",
"Specific oral tolerance induction in children with very severe cow's milk-induced reactions.",
"Cow's milk-specific cellular and humoral immune responses and atopy skin symptoms in infants from atopic families fed a partially (pHF) or extensively (eHF) hydrolyzed infant formula.",
"Oral desensitization as a useful treatment in 2-year-old children with cow's milk allergy.",
"Allergy development and macromolecular absorption in infants with different feeding regimens during the first three days of life. A three-year prospective follow-up.",
"A novel infant formula milk with added long-chain polyunsaturated fatty acids from single-cell sources: a study of growth, satisfaction and health."
] |
[
"The potential of extensively or partially hydrolyzed formulas to reduce the risks for allergies is controversial.\n We sought to assess the preventive effect of differently hydrolyzed formulas compared with cow's milk formula (CMF) in high-risk infants.\n Between 1995 and 1998, 2252 infants with a hereditary risk for atopy were enrolled in the German Infant Nutritional Intervention Study and randomly assigned at birth to one of 4 blinded formulas: CMF, partially hydrolyzed whey formula, extensively hydrolyzed whey formula, and extensively hydrolyzed casein formula (eHF-C). The primary end point at 1 year of age was the presence of allergic manifestation, which was defined as atopic dermatitis (AD), gastrointestinal manifestation of food allergy, allergic urticaria, or a combination of these factors.\n At 12 months per protocol, analysis was performed on 945 infants exposed to study formula: 304 (13.5%) infants had left the study, 138 (6.1%) infants were excluded because of noncompliance, and 865 infants were exclusively breast-fed the first 4 months of life. The incidence of allergic manifestation was significantly reduced by using eHF-C compared with CMF (9% vs 16%; adjusted OR, 0.51; 95% CI, 0.28-0.92), and the incidence of AD was significantly reduced by using eHF-C (OR, 0.42; 95% CI, 0.22-0.79) and partially hydrolyzed whey formula (OR, 0.56; 95% CI, 0.32-0.99). Family history of AD was a significant risk factor and modified the preventive effect of the hydrolysates.\n Prevention of allergic diseases in the first year of life is feasible by means of dietary intervention but influenced by family history of AD. The preventive effect of each hydrolyzed formula needs to be clinically evaluated.",
"The aim of this study was to compare the allergy-preventive effect of a partially hydrolyzed formula with two extensively hydrolyzed formulas, in infants with a high risk for development of allergic disease. High-risk infants from four Danish centres were included in the period from June 1994 to July 1995. Five-hundred and ninety-five high-risk infants were identified. High-risk infants were defined as having biparental atopy, or a single atopic first-degree relative combined with cord blood immunoglobulin E (IgE)> or =0.3 kU/l. At birth all infants were randomized to one of three different blinded formulas. All mothers had unrestricted diets during pregnancy and lactation and were encouraged to breast-feed exclusively. If breast-feeding was insufficient, one of the three formulas, according to randomization, was given during the first 4 months. It was recommended not to introduce cow's milk, cow's milk products. and solid foods until the age of 4 months. After the age of 4 months a normal unrestricted diet and conventional cow's milk-based formula were given when needed. All infants were followed-up prospectively with interview and physical examination at the age of 6, 12, and 18 months, and if any possible atopic symptoms were reported. If food allergy was suspected, controlled elimination/challenge procedures were performed in a hospital setting. Of 550 infants included in the study, 514 were seen at all visits and 36 were excluded owing to noncompliance. Of 478 infants who completed the study, 232 were exclusively breast-fed, 79 received an extensively hydrolyzed casein formula (Nutramigen), 82 an extensively hydrolyzed whey formula (Profylac), and 85 a partially hydrolyzed whey formula (Nan HA), during the first 4 months of life. These four groups were identical in regard to atopic predisposition, cord blood IgE, birthplace, and gender. Exclusively breast-fed children were exposed less to tobacco smoke and pets at home and belonged to higher social classes, whereas the three formula groups were identical concerning environmental factors. The frequency of breast-feeding was high; only eight (2%) children were not breast-fed at all. The three formula groups were identical in regard to duration of breast-feeding and age at introduction of formula and solid foods. No significant differences were found in the three groups of infants receiving formula milk regarding the cumulative incidence of atopic dermatitis or respiratory symptoms. The cumulative incidence of parental-reported cow's milk allergy was significantly higher in children fed partially hydrolyzed formula (Nan HA) compared with extensively hydrolyzed formula (Nutramigen or Profylac) at 12 and 18 months (NanHA, 7.1%; Nutramigen, 2.5%; Profylac, 0%; p=0.033). The cumulative incidence of confirmed cow's milk allergy was 1.3% (three of 232) in exclusively breast-fed infants, 0.6% (one of 161) in infants fed extensively hydrolyzed formula (Nutramigen or Profylac), and 4.7%(four of 85) in infants fed partially hydrolyzed formula (Nan HA). Partially hydrolyzed formula was found to be less effective than extensively hydrolyzed formula in preventing cow's milk allergy, 0.6% vs. 4.7% (p=0.05), but because of the small number of cases the results should be interpreted with caution. Compared with other similar studies the frequency ofatopic symptoms was low, even though the dietetic intervention did not include either maternal diet during lactation or dietary restrictions to the children after the age of 4 months.",
"The allergy preventive effect of extensively (N) and partially (PH) hydrolysed cows' milk formulas compared with a regular formula (RM) was assessed in 155 infants with a family history of allergy. No cows' milk was given during the first nine months of life and no egg and fish up to 12 months of age. Breast feeding mothers avoided the same foods. At weaning the infants were randomised to one of the formula groups. The cumulative incidence of atopic symptoms at 18 months was 51, 64, and 84% in the N, PH, and RM groups, respectively. From 6 to 18 months there were significantly less cumulative atopic symptoms in the N group compared with the RM group, and significantly less than the PH group up to 6 (N = 25%; PH = 46%) and 9 months (N = 34%, PH = 58%). At 9 months significantly fewer infants in the N group (10%) than in the PH group (33%) had a positive skin prick test to eggs. The findings support an allergy preventive effect of an extensively hydrolysed formula, but not of a partially hydrolysed formula, during the first 18 months of life of high risk infants.",
"To determine the antigenicity, nutritional adequacy, and growth-promoting efficacy of protein hydrolysate or amino acid-derived formulas in infants with cow milk allergy.\n Several protein hydrolysate or amino acid-derived formulas were graded for beta-lactoglobulin content and skin reactivity in 74 atopic children with cow milk allergy proved by a double-blind, placebo-controlled challenge. A randomized, prospective follow-up study of 9 months included 22 infants with a mean age of 6 months (95% confidence interval, 4 to 7), who were fed an extensively hydrolyzed whey formula (group We), and 23 infants with a mean age of 17 (95% confidence interval, 4 to 7) months, who were given an amino acid-derived formula (group AA).\n Both formulas were clinically and biochemically tolerated. The mean concentration of essential amino acids in plasma was lower in group We but higher in group AA compared with values for breast-fed control infants (p = 0.001). There was a different trend between the groups in weight (p = 0.09) and length (p = 0.006). Growth was promoted in group AA during the follow-up; it was constant during the first months, followed by a gradual decline in rate in group We. In both groups, atopic eczema improved significantly and progressively, and a downward trend was found in serum total and milk-specific IgE concentrations, proving the efficacy of both formulas.\n Extensively hydrolyzed formulas are safe and effective for most infants; an amino acid-derived formula may be preferable for infants with multiple food allergies, especially for the maintenance of normal growth.",
"Early feeding with cow's milk (CM) may increase the risk of cow's milk allergy (CMA).\n We sought to examine prospectively whether supplementary feeding of CM at the maternity hospital would increase the risk when compared with feeding with pasteurized human milk or hydrolyzed formula.\n We studied 6209 unselected healthy, full-term infants, of whom 5385 (87%) required supplementary milk while in the hospital. The infants were randomly assigned to receive CM formula (1789 infants), pasteurized human milk (1859 infants), or whey hydrolysate formula (1737 infants). The comparison group (824 infants) was composed of infants who were exclusively breast-fed. The infants were followed for 18 to 34 months for symptoms suggestive of CMA. The primary endpoint was a challenge-proven adverse reaction to CM after a successful CM elimination diet.\n The cumulative incidence of CMA in the infants fed CM was 2.4% compared with 1.7% in the pasteurized human milk group (odds ratio [OR], 0.70; 95% confidence interval [CI], 0. 44-1.12) and 1.5% in the whey hydrolysate group (OR, 0.61; 95% CI, 0. 38-1.00). In the comparison group, CMA developed in 2.1% of the infants. Among the infants who required supplementary feeding at hospital, both exposure to CM while in the hospital (OR, 1.54; 95% CI, 1.04-2.30; P =.03) and obvious parental atopy (OR, 2.32; 95% CI, 1.53-3.52; P <.001) increased the risk of CMA.\n Our data indicate that feeding of CM at maternity hospitals increases the risk of CMA when compared with feeding of other supplements, but exclusive breast-feeding does not eliminate the risk.",
"We evaluated the immunogenicity and antigenicity of a formula based on partially hydrolyzed cow's milk whey protein in infants at risk of atopy and in controls. Total IgE and specific IgE, IgG, and IgG4 subclass antibodies against egg albumin and cow's milk alpha-lactalbumin, casein, and beta-lactoglobulin were measured by radioimmunoassay of cord blood and of peripheral blood at 5 days and 6 months of life in five groups of infants: 16 breast-fed infants at risk of atopy (group 1), 21 partially hydrolyzed whey formula-fed infants at risk of atopy (group 2), 14 formula-fed infants at risk of atopy (group 3), 10 breast-fed control infants (group 4), and 13 formula-fed control infants (group 5). Total IgE concentration was significantly lower in group 2 at 6 months than in groups 3 and 5 infants and similar to that observed in groups 1 and 4 infants. The concentration of specific antiegg and anti-cow's milk protein IgG and of specific anti-cow's milk alpha-lactalbumin and beta-lactoglobulin IgG4 subclass antibodies was significantly reduced in group 2 as compared to group 3 infants and similar to that found in breast-fed infants. In conclusion, the partially hydrolyzed formula was less immunogenic and antigenic than a traditional formula and was as immunogenic and antigenic as breast milk.",
"This prospective, long-term study assessed the effects of a protein hydrolysate formula on allergy prevention in infants with a family history of allergy. Infants were randomly assigned to receive either the hydrolysate formula (n = 92) or an adapted cow milk formula (n = 85) alone or with breast-feeding for 4 months. The groups did not differ in family allergy history scores or cord blood IgE levels. After 4 months, total IgE levels and allergic reactions did not differ significantly between groups, although the hydrolysate group had a lower prevalence of eczema. At 12 months of age, neither IgE levels nor allergic reactions were significantly different. At 2 years of age, however, 18 allergic reactions had occurred in the hydrolysate group and 31 had occurred in the control group; the differences were significant for eczema (p < 0.001) but not for asthma. At 4 years of age, allergic signs were found in 11 children in the hydrolysate group and in 17 children in the control group; the difference was significant only for eczema (p < 0.01). These results suggest that early feeding of a protein hydrolysate formula to infants at risk for allergies had a long-term preventive effect on the prevalence of eczema but not of asthma.",
"The incidence of atopic manifestations was analyzed in infants \"at risk\" because of histories of atopy in first degree relatives. The incidence of atopic manifestations was significantly reduced (P = .0011) during the first 6 months of life when only the whey hydrolysate was administered (2/32 infants, 6.3%) compared with the incidence when an adapted formula was given (14/35 infants, 40%). This beneficial effect continued during the 6 to 12-month period, after diversification of the diet at 6 months. At the age of 1 year, 7/32 (21.8%) of the infants in the whey hydrolysate group had presented with manifestations of probable atopic disease compared with 17/35 (48.6%) infants in the adapted formula group (P = .021). The incidence of cow milk protein sensitivity was evaluated at 5/32 (15.6%) in the hydrolysate group and 15/35 (42.8%) in the adapted formula group (P = .014). Other foods such as egg and fish may be responsible for manifestations in three infants in hydrolysate group and in five infants of the adapted group (9.4% and 14.3%, respectively NS). These preliminary data show that the administration of a whey hydrolysate during the first 6 months of life to babies \"at risk\" decreased the incidence of atopic disease up to the age of 12 months. The incidence of cow milk protein sensitivity appeared to be decreased, whereas the incidence of sensitivities to other food proteins was comparable in both groups.",
"Cow's milk allergy (CMA) in children is a important problem in medical practice. Oral desensitization has been proposed as a therapeutic approach, but current protocols are time-consuming and impractical.\n To establish a patient-friendly desensitization regimen with weekly up-dosing and to evaluate it in a randomized controlled trial.\n Thirty children with IgE-mediated CMA confirmed by double-blind placebo-controlled food challenge were equally randomized to desensitization with CM or soy milk as control. The weekly up-dosing lasted 18 weeks. The occurrence and severity of reactions after each dose was evaluated, and the desensitization was stopped if severe reactions occurred. Specific IgE and IgG4 levels to CM were measured at baseline, after 8 weeks, and at the end of the study. The double-blind food challenge was repeated once the desensitization was completed or after premature discontinuation.\n Two active and 1 control patient dropped out. Full tolerance to CM (200 mL) was achieved in 10 active patients and partial tolerance in 1. Two active patients discontinued the desensitization after experiencing severe reactions, whereas no reactions occurred in controls, whose sensitivity to CM remained unchanged. A significant increase in specific IgG4 levels was found only in the active group.\n This weekly up-dosing desensitization protocol for CMA performed under medical supervision was effective and reasonably safe and induced consistent immunologic changes.\n Copyright © 2010 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.",
"To study the influence of hypoallergenic milk on the occurrence of allergic diseases, thirty-three high risk, normal full-term newborns were divided into two groups with comparable family allergy score (FAS) and cord serum IgE. Group A consisted of 18 babies fed since birth with regular formula, while group B included 15 babies fed breast milk and/or NAN H.A. (Hypoallergenic infant formula) for the first 6 months of life. Close clinical observations for the appearance of atopic dermatitis, allergic rhinitis and wheezing as well as serial examination of total serum IgE and milk-specific IgE antibodies were done during the first year of life. The results showed: 1) Infants fed regular formula had a higher incidence of moderate to severe atopic dermatitis (AD) and allergic rhinitis (AR) than those fed NAN H.A. (39% vs 13% for AD; and 33% vs 13% for AR), but the difference was not significant. There was no difference in the incidence of wheezing between these two groups; 2) There was no relationship between cord blood IgE and FAS; 3) Neither the cord blood IgE nor FAS influenced the occurrence of allergic diseases and total serum IgE at one year of age; 4) Hypoallergenic milk (NAN H.A.) could support normal growth and development. In conclusion, a higher incidence of moderate to severe AD and AR was found in high risk infants fed regular formula than in those fed hypoallergenic milk. However, a study with a larger number of babies and a longer period of follow-up is needed to obtain a solid conclusion.",
"One hundred-eight infants from atopic families were admitted to the study. Each had at least one first-degree relative affected by asthma or rhinitis, conjunctivitis, eczema, cow's milk protein intolerance. All infants not breast fed were hypoallergenic formula. 46 infants were breast fed, 39 were bottle fed by the ordinary formula and 23 received the hypoallergenic one. No other food was introduced up to 6 months. Cow's milk proteins, egg, poultry and fish were introduced after 6 months. All infants were followed up to 24 months. Incidence of allergic diseases up to 24 months was not significantly different among the 3 groups.",
"Cow's milk allergy/intolerance is treated by complete avoidance of cow's milk proteins. Because cow's milk is an important food for infants, its avoidance may lead to an increased risk of growth impairment. Whilst there is evidence for the beneficial effects of extensively hydrolyzed cow's milk formulate (eHF) in infants with cow's milk allergy/intolerance, little is known about the effects of amino-acid-based formulae (AA) in such infants. We therefore performed a prospective, controlled, multi-center trial to study the efficacy of AA in comparison with eHF, on the growth and clinical symptoms of 73 infants (median age 5.7 months) with cow's milk allergy/intolerance and atopic dermatitis. Cow's milk allergy/intolerance was proven in all infants by double-blind, placebo-controlled food-challenge. We observed a significant improvement in the SCORAD index in both groups, from a mean of 24.6, at entry, to a mean of 10.7 (p < 0.0001) after 6 months. In the AA group there was a significant increase in the length standard deviation score (p < 0.04), whilst there was no difference in the eHF group. The weight-for-length values were stable in both groups. The energy intake during the study was similar in both groups. Both an AA and eHF resulted in a significant clinical improvement in infants with an early onset of symptoms of cow's milk allergy/intolerance. Feeding an AA resulted in improved growth compared with feeding eHF, despite similar dietary intakes, and may therefore be considered as a beneficial alternative in infants with severe cow's milk allergy intolerance.",
"Some children allergic to cow's milk proteins (CMPs) experience exceptionally severe reactions after ingesting only trace amounts of antigen. Avoiding the food and carrying self-injectable epinephrine are the current strategies for their management.\n The aim of this study was to evaluate the safety and efficacy of specific oral tolerance induction (SOTI) for children with severe CMP-induced systemic reactions.\n Ninety-seven children aged 5 years or older with a history of severe allergic reactions and very high CMP-specific IgE levels were selected for a double-blind, placebo-controlled food challenge. Sixty had positive test results to very small amounts of milk and were randomly divided in 2 different groups. Thirty children (group A) immediately began SOTI, whereas the remaining 30 (group B) were kept on a milk-free diet and followed for 1 year.\n After 1 year, 11 (36%) of 30 children in group A had become completely tolerant, 16 (54%) could take limited amounts of milk (5-150 mL), and 3 (10%) were not able to complete the protocol because of persistent respiratory or abdominal complaints. In group B the result of the double-blind, placebo-controlled food challenge performed after a year was positive in all 30 cases (P < .001).\n In this study SOTI was effective in a significant percentage of cases.",
"Hydrolyzed milk formulas are recommended to feed infants at high risk of atopy if breast-feeding is not possible. We studied the specific cellular and humoral immune response to cow's milk proteins and occurrence of atopic dermatitis under different feeding regimens: two hydrolyzed infant milk formulas (partially [pHF] and extensively hydrolyzed [eHF]) and under exclusive breast-feeding (BF).\n Seventy-two infants from families with atopic symptoms were randomized in the pHF and eHF groups, respectively. At 6 and 12 months of age, peripheral blood mononuclear cell proliferation along with specific IgG and IgE to cow's milk proteins was determined in infants fed pHF or eHF, respectively, and those who had not yet received any formula at 6 months of age (BF). Cases of atopic dermatitis were recorded throughout the first 12 months of life, and their severity was evaluated with SCORAD points.\n A significantly decreased proliferation to cow's milk caseins was found in the pHF group compared to the exclusively breast-fed group. Medians of stimulation indexes for CAS at 6 months were as follows: pHF 1.18; n=24; BF 1.70; n=24 (P=0.033, Mann-Whitney U-test). Higher levels of plasma IgG antibodies to BCAS were found in infants fed pHF than in those fed eHF at 12 months. Optical density (OD): (25th percentile; median; 75th percentile): pHF: 0.00; 0.14; 0.38; n=30; eHF: 0.00; 0.03; 0.14; n=28; P=0,089, Mann-Whitney U-test. Cow's milk-specific IgE was detected at 6 months as follows: BF: 3 of 24; eHF: 2 of 21; pHF: 0 of 23. The number of cases of atopic dermatitis and their severity did not differ among the groups during the first 12 months.\n Feeding pHF appears to suppress cow's milk-specific cellular responses and stimulate specific IgG production. Specific IgE sensitization can occur also with breast-feeding.",
"Limited published evidence shows oral desensitization to be a potential intervention option for cow's milk protein (CMPs) allergy.\n The aim of this study was to evaluate the safety and efficacy of oral desensitization in 2-year-old children with cow's milk allergy, as a treatment alternative to elimination diet.\n A total of 60 children aged 24-36 months with IgE-mediated allergy to CMPs were included in this multi-center study and were randomized into two groups. Thirty children (group A: treatment group) began oral desensitization immediately, whereas the remaining 30 (group B: control group) were kept on a milk-free diet and followed-up for 1 year.\n After 1-year follow-up period, 90% of the children in group A had become completely tolerant vs. 23% of the children in group B. In group A, cow's milk skin reactivity and serum-specific IgE to milk and casein decreased significantly from the initial assessment, whereas group B showed no significant change after 1 year of follow-up. Twenty-four patients (80%) developed some reaction during the treatment period: 14 children developed moderate reaction (47%) and 10 mild reaction (33%). The most common manifestations were urticaria-angioedema, followed by cough.\n In this study, oral desensitization was found to be effective in a significant percentage of 2-year-old children with cow's milk allergy. Oral desensitization appears to be efficacious as an alternative to elimination diet in the treatment of 2-year-old children with cow's milk allergy. The side-effect profile appears acceptable but requires further study.\n © 2011 Blackwell Publishing Ltd.",
"A group of 129 infants were randomly assigned at birth to one of three feeding regimens: human milk (HM), cow's milk formula (CMF) or a casein hydrolysate formula (CHF) during the first 3 days of life. Blood samples were taken on at 4 days and at 2, 4, 8, 12 and 24 months of age. Macromolecular absorption was analysed by measuring the serum concentration of human alpha-lactalbumin (S-alpha-LA) with a competitive radioimmunoassay (RIA). Total serum IgE was measured by RIA. A family history of allergy correlated to the proportion of infants with allergic symptoms both at 24 and 36 months of age (p = 0.03 and p = 0.04 respectively). In none of the three groups did correlation exist between the duration of breastfeeding and serum alpha-LA, serum IgE, family history of allergy, frequency of allergic symptoms and proportion of infants with infections.",
"To evaluate the growth, feeding and health of babies fed a novel infant formula milk with added long chain polyunsaturated fatty acids (LCPs) produced from single-cell sources, at concentrations similar to those found in mature breast milk.\n Randomized double-blind control trial.\n One-hundred and forty healthy, full-term infants of birth weight 2.5-4.5 kg born at the Maternity Department, East Glamorgan General Hospital, Wales, whose mothers had already decided to bottle feed.\n Subjects were randomized to two groups; one (control group) to receive a standard formula milk and the other to receive the trial milk with added LCPs. Milks were supplied in a double-blind fashion and given for the first 12 weeks of life. Anthropometric measurements were made at recruitment, 3 months, 6 months and 1 y. Feeding diaries were completed at 6 weeks and 3 months, and a parental record was kept of any ill health suffered by the subjects during the first year of life.\n Of 140 infants recruited, 31 did not complete the protocol. Small but statistically significant differences were found only in the subscapular skinfold thickness at 6 weeks and 3 months, that in the trial group being slightly higher, but unlikely to be of any clinical importance. No differences were found in the feeding patterns of the infants in the two groups. Stool patterns were similar, as were the frequencies of illness and allergy.\n This study supports the view that LCPs from single-cell sources do not have detrimental effects on the growth, feeding and general health of infants."
] |
There is no evidence to support feeding with a hydrolysed formula for the prevention of allergy compared to exclusive breast feeding. In high risk infants who are unable to be completely breast fed, there is limited evidence that prolonged feeding with a hydrolysed formula compared to a cow's milk formula reduces infant and childhood allergy and infant CMA. In view of methodological concerns and inconsistency of findings, further large, well designed trials comparing formulas containing partially hydrolysed whey, or extensively hydrolysed casein to cow's milk formulas are needed.
|
CD003823
|
[
"8198936",
"7608310",
"16647628",
"19225038",
"12435255",
"10480473",
"10338459",
"7662226",
"11855793",
"17591533",
"9635947",
"3142396",
"11347755",
"11775134",
"9469797",
"16580575",
"17161769",
"9607384",
"9740480",
"12692572",
"2969315",
"12709466",
"7527104",
"12875478",
"1331444",
"1325010",
"7564362",
"8458113",
"11353877",
"9493699",
"15766995",
"13678870",
"18396107",
"10082500",
"8167383",
"9794352",
"16801465",
"9607383",
"2427835",
"7527107",
"1599343",
"12761258",
"6432119",
"7927956",
"9476035",
"16882058",
"11849464",
"6313522",
"1708060",
"3063797",
"18378519",
"2442550",
"15514192",
"8062609",
"8018001",
"16114784",
"7795830",
"8803515",
"17928878",
"2892881",
"3951807",
"11079287",
"19543080",
"1704983",
"11320369",
"17379047",
"9297994",
"8817406",
"9052345",
"10835440",
"10437863",
"11422755",
"3061819",
"15917336",
"7486272",
"15975107",
"19135567",
"9250456",
"17425758"
] |
[
"Dose finding studies with imidapril--a new ACE inhibitor.",
"Tricenter assessment of the efficacy of the ACE inhibitor, moexipril, by ambulatory blood pressure monitoring.",
"Pharmaceutical care program for patients with uncontrolled hypertension. Report of a double-blind clinical trial with ambulatory blood pressure monitoring.",
"Lowering blood pressure reduces renal events in type 2 diabetes.",
"Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial.",
"Matrix study of irbesartan with hydrochlorothiazide in mild-to-moderate hypertension.",
"Augmented short- and long-term hemodynamic and hormonal effects of an angiotensin receptor blocker added to angiotensin converting enzyme inhibitor therapy in patients with heart failure. Vasodilator Heart Failure Trial (V-HeFT) Study Group.",
"Additive effects of verapamil and enalapril in the treatment of mild to moderate hypertension.",
"Efficacy of ACE inhibitors and ATII receptor blockers in patients with microalbuminuria: a prospective study.",
"ACE inhibitors and persistent left ventricular hypertrophy after renal transplantation: a randomized clinical trial.",
"Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group.",
"[Randomized, comparative study on the treatment of moderate arterial hypertension during pregnancy: methyldopa, acebutolol, labetalol].",
"Reduction of ACE activity is insufficient to decrease microalbuminuria in normotensive patients with type 1 diabetes.",
"Evaluation of the 24-hour blood pressure effects of eprosartan in patients with systemic hypertension.",
"The effect on 24 h blood pressure control of an angiotensin converting enzyme inhibitor (perindopril) administered in the morning or at night.",
"A factorial study of combination hypertension treatment with metoprolol succinate extended release and felodipine extended release results of the Metoprolol Succinate-Felodipine Antihypertension Combination Trial (M-FACT).",
"Effect of intensive blood pressure control with valsartan on urinary albumin excretion in normotensive patients with type 2 diabetes.",
"A randomized, double-blind, placebo-controlled, parallel-group, multicenter trial of four doses of tasosartan in patients with essential hypertension. Tasosartan Investigator's Group.",
"Valsartan in heart failure patients previously untreated with an ACE inhibitor.",
"Distinct time courses of renal protective action of angiotensin receptor antagonists and ACE inhibitors in chronic renal disease.",
"The effects of the long-acting angiotensin-converting enzyme inhibitor cilazapril on casual, exercise, and ambulatory blood pressure.",
"Effects of comprehensive lifestyle modification on blood pressure control: main results of the PREMIER clinical trial.",
"Efficacy and tolerance of trandolapril (0.5-2 mg) administered for 4 weeks in patients with mild-to-moderate hypertension. Investigator Study Group.",
"Treatment of isolated systolic hypertension: the SHELL study results.",
"Twenty-four hour blood pressure effect of once-daily lisinopril, enalapril, and placebo in patients with mild to moderate hypertension.",
"Treatment of arterial hypertension in diabetic humans: importance of therapeutic selection.",
"Double-blind comparison of antihypertensive treatment with ramipril and piretanide, given alone or in combination.",
"Fosinopril monotherapy: relationship between blood pressure reduction and time of administration.",
"Early ACE-i intervention in microalbuminuric patients with type 1 diabetes: effects on albumin excretion, 24 h ambulatory blood pressure, and renal function.",
"Evaluation of the efficacy and tolerability of a low-dose combination of isradipine and spirapril in the first-line treatment of mild to moderate essential hypertension.",
"Blood-pressure control for renoprotection in patients with non-diabetic chronic renal disease (REIN-2): multicentre, randomised controlled trial.",
"Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial.",
"Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial.",
"ACE inhibitor versus beta-blocker for the treatment of hypertension in renal allograft recipients.",
"ACE inhibitor mediated reductions in renal size and microalbuminuria in normotensive, diabetic subjects.",
"Effects of candesartan cilexetil in patients with systemic hypertension. Candesartan Cilexetil Study Investigators.",
"Renal function and effectiveness of angiotensin-converting enzyme inhibitor therapy in patients with chronic stable coronary disease in the Prevention of Events with ACE inhibition (PEACE) trial.",
"Comparative efficacy of two angiotensin II receptor antagonists, irbesartan and losartan in mild-to-moderate hypertension. Irbesartan/Losartan Study Investigators.",
"A comparison of celiprolol and chlorthalidone in hypertensive patients with reversible bronchial obstruction.",
"Double-blind comparison of the efficacy and safety of trandolapril 2 mg and hydrochlorothiazide 25 mg in patients with mild-to-moderate essential hypertension. Investigator Study Group.",
"Nonpharmacologic intervention to reduce blood pressure in older patients with mild hypertension.",
"Treatment of IgA nephropathy with ACE inhibitors: a randomized and controlled trial.",
"Beta blockade, diuretics, and salt restriction for the management of mild hypertension: a randomised double blind trial.",
"Study of the efficacy and safety of the combination ramipril 2.5 mg plus hydrochlorothiazide 12.5 mg in patients with mild-to-moderate hypertension. ATHES Study Group.",
"Pharmacokinetics and pharmacodynamics of candesartan after administration of its pro-drug candesartan cilexetil in patients with mild to moderate essential hypertension--a population analysis.",
"Comparison of 25 and 75 mg/day naftopidil for lower urinary tract symptoms associated with benign prostatic hyperplasia: a prospective, randomized controlled study.",
"Effects of aggressive blood pressure control in normotensive type 2 diabetic patients on albuminuria, retinopathy and strokes.",
"Monotherapy of essential hypertension with a converting-enzyme inhibitor.",
"The effect of cilazapril, a new angiotensin converting enzyme inhibitor, on peak and trough blood pressure measurements in hypertensive patients.",
"Hypertensive emergencies in old age: effects of angiotensin converting enzyme inhibition.",
"Treatment of hypertension in patients 80 years of age or older.",
"Controlled multicenter study of the antihypertensive effects of lisinopril, hydrochlorothiazide, and lisinopril plus hydrochlorothiazide in the treatment of 394 patients with mild to moderate essential hypertension.",
"Different effects of antihypertensive regimens based on fosinopril or hydrochlorothiazide with or without lipid lowering by pravastatin on progression of asymptomatic carotid atherosclerosis: principal results of PHYLLIS--a randomized double-blind trial.",
"Effects of long-term enalapril treatment on persistent micro-albuminuria in well-controlled hypertensive and normotensive NIDDM patients.",
"A multifactorial trial design to assess combination therapy in hypertension. Treatment with bisoprolol and hydrochlorothiazide.",
"Pentoxifylline is as effective as captopril in the reduction of microalbuminuria in non-hypertensive type 2 diabetic patients--a randomized, equivalent trial.",
"Trial of Nonpharmacologic Intervention in the Elderly (TONE). Design and rationale of a blood pressure control trial.",
"Evaluation of the antihypertensive efficacy and tolerability of moexipril, a new ACE inhibitor, compared to hydrochlorothiazide in elderly patients.",
"A comparison of the efficacy and safety of irbesartan/HCTZ combination therapy with irbesartan and HCTZ monotherapy in the treatment of moderate hypertension.",
"Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial.",
"A comparison of two dose regimens of epsilon aminocaproic acid in the prevention and management of secondary traumatic hyphemas.",
"Effect of pharmacist intervention and initiation of home blood pressure monitoring in patients with uncontrolled hypertension.",
"Reduction of morning blood pressure surge after treatment with nifedipine GITS at bedtime, but not upon awakening, in essential hypertension.",
"Antihypertensive efficacy and tolerability of a fixed combination of metoprolol and felodipine in comparison with the individual substances in monotherapy. The Swedish/United Kingdom Study Group.",
"ADEPT: Addition of the AT1 receptor antagonist eprosartan to ACE inhibitor therapy in chronic heart failure trial: hemodynamic and neurohormonal effects.",
"Comparison of valsartan/hydrochlorothiazide combination therapy at doses up to 320/25 mg versus monotherapy: a double-blind, placebo-controlled study followed by long-term combination therapy in hypertensive adults.",
"Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators.",
"Effects of moderate salt restriction alone and in combination with cilazapril on office and ambulatory blood pressure.",
"Combined enalapril and felodipine extended release (ER) for systemic hypertension. Enalapril-Felodipine ER Factorial Study Group.",
"Effect of intravenous nimodipine on blood pressure and outcome after acute stroke.",
"Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria.",
"Long-term beneficial effect of ACE inhibition on diabetic nephropathy in normotensive type 1 diabetic patients.",
"Evaluation of the dose-effect relationship of a new ace inhibitor (perindopril) by an automatic blood pressure recorder.",
"Additive antiproteinuric effect of pentoxifylline in patients with type 2 diabetes under angiotensin II receptor blockade: a short-term, randomized, controlled trial.",
"[Comparison of effects of aprotinin and tranexamic acid on blood loss in heart surgery].",
"Does metformin decrease blood pressure in patients with Type 2 diabetes intensively treated with insulin?",
"Insulin sensitivity and lipid metabolism with oral contraceptives containing chlormadinone acetate or desogestrel: a randomized trial.",
"Evaluation of the efficacy and tolerability of nitrendipine in reducing both pressure and left ventricular mass in hypertensive type 2 diabetic patients.",
"Enalapril/amlodipine combination in cyclosporine-treated renal transplant recipients: a prospective randomized trial."
] |
[
"1. We describe an approach involving a smaller, shorter study, leading onto a longer, larger study in which the antihypertensive effects of ascending doses of imidapril, a new ACE inhibitor, were investigated. Both studies were planned prospectively, assuming a clinically useful fall in BP to be 8 mm Hg (s.d. = 9). The studies included patients with mild to moderate essential hypertension (baseline sitting diastolic blood pressure (SDBP) 95-115 mm Hg). After a placebo run-in of 2-3 weeks patients received either placebo or imidapril 2.5, 5, 10 or 20 mg in the 2 week study (n = 91) or imidapril 5, 10, 20 or 40 mg in the 4 week study (n = 162). 2. The overall mean baseline SDBP was 103.4 mm Hg (s.d. 0.62) in the initial study and 101.5 mm Hg (s.d. 0.41) in the 4 week study. 3. Compared with placebo, imidapril 10, 20 and 40 mg significantly reduced SDBP. There was no significant difference between these doses, suggesting that 10 mg achieved maximal ACE inhibition in most patients. The 2.5 mg dose showed no significant effect. The 5 mg dose gave an intermediate effect. In both studies the overall incidence of adverse events was similar in the imidapril and placebo groups, and was not worrying.",
"To assess the efficacy and time-dependent effects of once-daily moexipril, a nonsulfhydryl ester prodrug of the angiotensin-converting enzyme (ACE) inhibitor, moexiprilat, we conducted a multicenter, double-blind, placebo-controlled trial in 51 hypertensive patients using both clinic and ambulatory blood pressure (BP) recordings. Patients were included in the trial based on a minimum of 40% of the daytime diastolic BPs of 90 mm Hg or more during a placebo baseline phase; and the primary endpoint was change in 24-hour ambulatory diastolic BP. Patients were randomized to receive placebo, 7.5 mg of moexipril, or 15 mg of moexipril once daily. Clinic and ambulatory BPs were taken on the first day and after eight weeks of double-blind therapy. After the 7.5-mg dose, there were no significant changes in the acute or prolonged clinic BPs compared with placebo. Compared with adjusted mean changes for placebo, the 15-mg moexipril dose lowered clinic systolic BP, but not diastolic BP. In contrast, acute (1 day) reductions in 24-hour diastolic BPs were -2/-3 mm Hg, -6/-4 mm Hg, and -14/-9 mm Hg on placebo, 7.5 mg of moexipril, and 15 mg of moexipril, respectively (P < .01 for the 15-mg dose). Similarly, after long-term dosing for 8 weeks, reductions in 24-hour diastolic BPs were 1/-2 mm Hg, -6/-4 mm Hg, and -12/-9 mm Hg for the respective treatment groups (P < .01 for the 15-mg dose).(ABSTRACT TRUNCATED AT 250 WORDS)",
"Pharmaceutical care programs may be an option to improve blood pressure (BP) control in patients with uncontrolled hypertension. The aim of this study was to evaluate the efficacy of pharmaceutical care programs in treating patients with resistant hypertension.\n In a double-blind randomized clinical trial, 71 patients with uncontrolled BP were enrolled in a pharmaceutical care program or in a control group and underwent a series of cognitive tests. The primary outcome was change in ambulatory BP (ABP) between the baseline evaluation and the final visit 6 months later. The secondary outcomes were the frequency of drug-related problems and adherence as determined by plasma levels of hydrochlorothiazide.\n The delta-values between the intervention and control groups for ABP in the different daily periods, with the corresponding 95% confidence limits, adjusted for age and baseline BP were: 3 (-1 to 5), 2 (-2 to 4), and 5 (-1 to 6) mm Hg for 24 h, daily and nightly systolic BP, respectively. The corresponding values for diastolic BP were 1 (-1 to 3), 0 (-2 to 2), and 3 (-1 to 4) mm Hg, respectively. Hydrochlorothiazide was detected in the plasma in 21 of 27 patients in the intervention group that attended to all appointments and 24 of 30 patients in the control group (P = .904).\n The pharmaceutical care program tested in this trial was feasible and showed a trend for better BP control in patients with uncontrolled hypertension.",
"BP is an important determinant of kidney disease among patients with diabetes. The recommended thresholds to initiate treatment to lower BP are 130/80 and 125/75 mmHg for people with diabetes and nephropathy, respectively. We sought to determine the effects of lowering BP below these currently recommended thresholds on renal outcomes among 11,140 patients who had type 2 diabetes and participated in the Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study. Patients were randomly assigned to fixed combination perindopril-indapamide or placebo, regardless of their BP at entry. During a mean follow-up of 4.3 yr, active treatment reduced the risk for renal events by 21% (P < 0.0001), which was driven by reduced risks for developing microalbuminuria and macroalbuminuria (both P < 0.003). Effects of active treatment were consistent across subgroups defined by baseline systolic or diastolic BP. Lower systolic BP levels during follow-up, even to <110 mmHg, was associated with progressively lower rates of renal events. In conclusion, BP-lowering treatment with perindopril-indapamide administered routinely to individuals with type 2 diabetes provides important renoprotection, even among those with initial BP <120/70 mmHg. We could not identify a BP threshold below which renal benefit is lost.",
"Hypertension is a leading cause of end-stage renal disease (ESRD) in the United States, with no known treatment to prevent progressive declines leading to ESRD.\n To compare the effects of 2 levels of blood pressure (BP) control and 3 antihypertensive drug classes on glomerular filtration rate (GFR) decline in hypertension.\n Randomized 3 x 2 factorial trial with enrollment from February 1995 to September 1998.\n A total of 1094 African Americans aged 18 to 70 years with hypertensive renal disease (GFR, 20-65 mL/min per 1.73 m(2)) were recruited from 21 clinical centers throughout the United States and followed up for 3 to 6.4 years.\n Participants were randomly assigned to 1 of 2 mean arterial pressure goals, 102 to 107 mm Hg (usual; n = 554) or 92 mm Hg or less (lower; n = 540), and to initial treatment with either a beta-blocker (metoprolol 50-200 mg/d; n = 441), an angiotensin-converting enzyme inhibitor (ramipril 2.5-10 mg/d; n = 436) or a dihydropyridine calcium channel blocker, (amlodipine 5-10 mg/d; n = 217). Open-label agents were added to achieve the assigned BP goals.\n Rate of change in GFR (GFR slope); clinical composite outcome of reduction in GFR by 50% or more (or > or =25 mL/min per 1.73 m2) from baseline, ESRD, or death. Three primary treatment comparisons were specified: lower vs usual BP goal; ramipril vs metoprolol; and amlodipine vs metoprolol.\n Achieved BP averaged (SD) 128/78 (12/8) mm Hg in the lower BP group and 141/85 (12/7) mm Hg in the usual BP group. The mean (SE) GFR slope from baseline through 4 years did not differ significantly between the lower BP group (-2.21 [0.17] mL/min per 1.73 m2 per year) and the usual BP group (-1.95 [0.17] mL/min per 1.73 m2 per year; P =.24), and the lower BP goal did not significantly reduce the rate of the clinical composite outcome (risk reduction for lower BP group = 2%; 95% confidence interval [CI], -22% to 21%; P =.85). None of the drug group comparisons showed consistent significant differences in the GFR slope. However, compared with the metoprolol and amlodipine groups, the ramipril group manifested risk reductions in the clinical composite outcome of 22% (95% CI, 1%-38%; P =.04) and 38% (95% CI, 14%-56%; P =.004), respectively. There was no significant difference in the clinical composite outcome between the amlodipine and metoprolol groups.\n No additional benefit of slowing progression of hypertensive nephrosclerosis was observed with the lower BP goal. Angiotensin-converting enzyme inhibitors appear to be more effective than beta-blockers or dihydropyridine calcium channel blockers in slowing GFR decline.",
"The purpose of this study was to assess the safety and antihypertensive dose-response effects of irbesartan and hydrochlorothiazide (HCTZ) in patients with mild-to-moderate hypertension. After a 4- to 5-week single-blind placebo lead-in period, 683 patients with seated diastolic blood pressure (SeDBP) between 95 and 110 mm Hg were randomized to receive once-daily dosing with one of 16 different double-blind, fixed combinations of irbesartan (0, 37.5, 100, and 300 mg irbesartan) and HCTZ (0, 6.25, 12.5, and 25 mg HCTZ) for 8 weeks. The primary efficacy variable was the change from baseline in trough SeDBP after 8 weeks of therapy. Data were analyzed by response surface modeling. At Week 8, mean changes from baseline in trough SeDBP (mm Hg) ranged from -3.5 for placebo, -7.1 to -10.2 for the irbesartan monotherapy groups, -5.1 to -8.3 for the HCTZ monotherapy groups, and -8.1 to -15.0 for the combination groups. Irbesartan plus HCTZ produced additive reductions in both SeDBP and seated systolic BP, with at least one combination producing greater BP reduction than either drug alone (P < .001). All treatments were well tolerated; there were no treatment-related serious adverse events. Irbesartan tended to ameliorate the dose-related biochemical abnormalities associated with HCTZ alone. In conclusion, the combination of HCTZ in doses up to 25 mg with irbesartan, in doses up to 300 mg, is safe and produces dose-dependent reductions in BP.",
"ACE inhibitors may not adequately suppress deleterious levels of angiotensin II in patients with heart failure. An angiotensin receptor blocker added to an ACE inhibitor may exert additional beneficial effects.\n Eighty-three symptomatic stable patients with chronic heart failure receiving long-term ACE inhibitor therapy were randomly assigned to double-blind treatment with valsartan 80 mg BID, valsartan 160 mg BID, or placebo while receiving their usual ACE inhibitor therapy. Studies were performed before and after the first dose of the test drug and again after 4 weeks of therapy. A single dose of lisinopril was administered during study days to ensure sustained ACE inhibition. Compared with placebo, the first dose of valsartan 160 mg resulted in a significantly greater reduction in pulmonary capillary wedge pressure at 3, 4, and 8 hours and during the prespecified 4- to 8-hour interval after the dose and in systolic blood pressure at 2, 3, 6, 8, and 12 hours and 4 to 8 hours after the dose. A pressure reduction from valsartan 80 mg did not achieve statistical significance. After 4 weeks of therapy, net reductions in 0-hour trough pulmonary capillary wedge pressure (-4.3 mm Hg; P=0. 16), pulmonary artery diastolic pressure (-4.7 mm Hg; P=0.013), and systolic blood pressure (-6.8 mm Hg; P=0.013) were observed in the valsartan 160 mg group compared with placebo. After 4 weeks of therapy, plasma aldosterone was reduced by valsartan 80 mg BID (-52. 1 pg/mL; P=0.001) and 160 mg BID (-47.8 pg/mL; P<0.001) compared with placebo, and there was a trend for a reduction in plasma norepinephrine (-97 pg/mL; P=0.10). Seventy-four of the 83 patients completed the trial.\n Physiologically active levels of angiotensin II persist during standard long-term ACE inhibitor therapy.",
"A factorial design was applied in this multicenter, double-blind, placebo-controlled trial of the calcium-channel blocker verapamil and the ACE inhibitor enalapril to assess the hypotensive effects of the combination compared with monotherapy, to evaluate safety, and to determine the effects on quality of life (QOL) of both drugs, alone and in combination. The study consisted of a 3 x 2 factorial design wherein 186 men and women with a sitting diastolic blood pressure (BP) of between 95 mm Hg and 114 mm Hg, after a 4-week placebo washout, were randomized to one of six treatment groups for 4 weeks of active treatment. Monotherapy with both 240 mg verapamil and 10 mg enalapril reduced systolic and diastolic BP to a similar extent and significantly more than placebo. The 240 mg verapamil + 10 mg enalapril combination was additive for both systolic and diastolic blood pressure; 120 mg verapamil + 10 mg enalapril was additive for systolic BP only. The total number of adverse events reported was similar for all six treatment groups. QOL scores were unchanged from baseline and not different between treatment groups. The combination of 240 mg verapamil and 10 mg enalapril was significantly more effective at reducing BP than either drug alone; this additivity of effect was not linked to a higher rate of adverse experiences or to a deterioration in QOL. Thus, combination therapy at lower doses may offer an alternative treatment option to higher dose monotherapy.",
"We compared the efficacy of treatment protocols with an angiotensin converting enzyme (ACE) inhibitor alone (enalapril, 5 mg) or angiotensin II (ATII) receptor blocker (losartan, 50 mg) or both enalapril plus losartan in patients with microalbuminuria in a prospective, randomized clinical trial. Normotensive type 2 diabetic patients with microalbuminuria documented by at least 3 consecutive urinary albumin excretion analyses were recruited for the study. Patients were grouped randomly into one of the protocols which consisted of treatment with 5 mg enalapril daily (group 1; n=12), 50 mg losartan daily (group 2; n=12) or both drugs (group 3; n=10). They were reevaluated with regard to HbA1c levels, lipid profiles, blood pressure and urinary albumin excretion rates (UAER) at 3-month intervals for 12 months. Mean age, duration of diabetes, body mass index, plasma lipid profiles and blood pressure levels were similar at the initial visit. In group 1, UAER returned to normal levels in 10 patients. Normalization of UAER occurred in 8 and 7 patients in groups 2 and 3, respectively. Percentage of reduction in UAERs at the end of 12 months were 58%, 59% and 60% (p=0.0001; p=0.0002; p=0.0003, respectively). The amount of reduction in UAER did not differ significantly among the three groups (p=0.346). ACE inhibitors and angiotensin II receptor blockers have similar efficacy in treating diabetic microalbuminuria, and the combination of the two drugs does not add any further benefit.",
"Interventional studies of left ventricular hypertrophy (LVH) in renal transplant recipients are scarce and to date evaluated only patients immediately after renal transplantation.\n Randomized controlled trial that assessed the effectiveness of angiotensin-converting enzyme (ACE) inhibitors in regressing persistent LVH after successful transplantation.\n 70 renal transplant recipients (47 men; age, 30 to 68 years) without diabetes previously randomly assigned to either cyclosporine or tacrolimus therapy, with LVH persisting 3 to 6 months after transplantation.\n Subjects were randomly assigned to either lisinopril (ACE-inhibitor group; 36 patients) or no therapy (control group; 34 subjects).\n Main outcome was change in left ventricular mass index (LVMi) at month 18.\n A consistent decrease in both systolic (SBP) and diastolic blood pressure (DBP) was observed in both groups (between-group differences, -1.7 +/- 3.3 mm Hg; 95% confidence interval [CI], -4.8 to 8.2; P = 0.6 for SBP; 0.3 +/- 2.2 mm Hg; 95% CI, -4.8 to 4.1; P = 0.9 for DBP), whereas LVMi regressed more in the ACE-inhibitor group (between-group difference, 10.1 +/- 16.3 g/m(2.7); 95% CI, 4.2 to 16.1; P < 0.01). A significant interaction of ACE inhibitors with cyclosporine in affecting LVMi change was shown by means of post hoc multiple regression analysis (P < 0.01; differences between cyclosporine and tacrolimus group, 13.3 +/- 3.9 g/m(2.7); 95% CI, 5.3 to 21.2; P < 0.01 in the ACE-inhibitor group; 3.7 +/- 4.2 g/m(2.7); 95% CI, -4.7 to 12.2; P = 0.4 in the control group).\n Single-center study with small sample size. Interaction of ACE inhibitors with cyclosporine treatment emerged from post hoc analysis.\n A prolonged course of ACE-inhibitor therapy is effective in regressing the persistent LVH of renal transplant recipients by mechanisms independent of effects on BP. This regression seems to be at least in part the effect of an interaction between ACE inhibitors and cyclosporine.",
"Despite treatment, there is often a higher incidence of cardiovascular complications in patients with hypertension than in normotensive individuals. Inadequate reduction of their blood pressure is a likely cause, but the optimum target blood pressure is not known. The impact of acetylsalicylic acid (aspirin) has never been investigated in patients with hypertension. We aimed to assess the optimum target diastolic blood pressure and the potential benefit of a low dose of acetylsalicylic acid in the treatment of hypertension.\n 18790 patients, from 26 countries, aged 50-80 years (mean 61.5 years) with hypertension and diastolic blood pressure between 100 mm Hg and 115 mm Hg (mean 105 mm Hg) were randomly assigned a target diastolic blood pressure. 6264 patients were allocated to the target pressure < or =90 mm Hg, 6264 to < or =85 mm Hg, and 6262 to < or =80 mm Hg. Felodipine was given as baseline therapy with the addition of other agents, according to a five-step regimen. In addition, 9399 patients were randomly assigned 75 mg/day acetylsalicylic acid (Bamycor, Astra) and 9391 patients were assigned placebo.\n Diastolic blood pressure was reduced by 20.3 mm Hg, 22.3 mm Hg, and 24.3 mm Hg, in the < or =90 mm Hg, < or =85 mm Hg, and < or =80 mm Hg target groups, respectively. The lowest incidence of major cardiovascular events occurred at a mean achieved diastolic blood pressure of 82.6 mm Hg; the lowest risk of cardiovascular mortality occurred at 86.5 mm Hg. Further reduction below these blood pressures was safe. In patients with diabetes mellitus there was a 51% reduction in major cardiovascular events in target group < or =80 mm Hg compared with target group < or =90 mm Hg (p for trend=0.005). Acetylsalicylic acid reduced major cardiovascular events by 15% (p=0.03) and all myocardial infarction by 36% (p=0.002), with no effect on stroke. There were seven fatal bleeds in the acetylsalicylic acid group and eight in the placebo group, and 129 versus 70 non-fatal major bleeds in the two groups, respectively (p<0.001).\n Intensive lowering of blood pressure in patients with hypertension was associated with a low rate of cardiovascular events. The HOT Study shows the benefits of lowering the diastolic blood pressure down to 82.6 mm Hg. Acetylsalicylic acid significantly reduced major cardiovascular events with the greatest benefit seen in all myocardial infarction. There was no effect on the incidence of stroke or fatal bleeds, but non-fatal major bleeds were twice as common.",
"The aim of this prospective, monocentric, opened study and with random order for antihypertensive sequence was to compare a betablocker with sympathomimetic activity (ACE) and an alphabetablocker (LAB) to the gold standard treatment (MD) in moderate HDP (BP greater than 90 mmHg). This study (January 1984 to December 1985) includes 63 women, mean age 28.2 years, divided into three comparable subgroups (age, parity, risk factors and initial level of SBP/DBP). Initial doses are 500 mg/bid (MD), and 400 mg/bid (ACE, LAB) and optimal dosages could not be respectively more than 1500 mg/bid (MD) or 1200 mg/bid (ACE, LAB). Usual criteria for maternal and foetal care are taken into account. The chi 2 test, the Student \"t\" test and the Kruskall Wallis test were used for statistical analysis. The results show: 1--A similar antihypertensive effect for MD and LAB, but significantly less for ACE (initial PAD-37th week PAD: MD +/- 18.8 +/- 2; LAB = -17.9 +/- 3; ACE = - 8.2 +/- 2.7 mmHg, p less than 0.02; 2--A more frequent adjustment of daily dosage with MD (n = 15) than with ACE (n = 10) or LAB (n = 7); 3--The absence of any significant difference for uricemia level, platelet counts, foetal cardiac rythm, and occurrence of pre-eclampsia (MD = 4; ACE = 3; LAB = 4; 4--An equivalent birth-weight (MD = 3110 +/- 628 g; ACE = 3115 +/- 645.(ABSTRACT TRUNCATED AT 250 WORDS)",
"To study whether administration of 1.25 and 5.0 mg ramipril daily, compared with placebo treatment, reduces the urinary albumin excretion rate (UAER) in normotensive patients with type 1 diabetes.\n Ramipril was administered double blind at two different doses (1.25 [n = 19] and 5.0 mg [n = 18]), and compared with placebo (n = 18) after a single-blind placebo period of 1-4 weeks. The patients (total, n = 55; women, n = 14) were followed for 2 years. To document an effect on the renin-angiotensin system, ACE activity and plasma-renin activity (PRA) were measured. In addition, 24-h ambulatory blood pressure (BP) was recorded at baseline and repeated after 1 and 2 years using a Spacelab 90207 ambulatory BP recording device (Spacelab, Redmont, CA).\n Both doses of ramipril were sufficient to reduce ACE activity and to increase PRA significantly as compared with placebo (P < 0.05 for both). On the other hand, neither ambulatory nor clinic BP was affected by either dose of ramipril compared with the placebo group. There was no progression of UAER in the placebo group during the 2 years of the study. Analysis of covariance showed no differences in UAER between the three treatment groups at year 1 (P = 0.94) or year 2 (P = 0.97), after adjusting for baseline. Furthermore, there were no statistically significant changes from baseline UAER within any of the three treatment groups.\n Treatment with ramipril did not affect microalbuminuria or clinic or ambulatory BP in this study. On the basis of the present study, we question the clinical use of ACE inhibitors in stably normotensive patients with type 1 diabetes and microalbuminuria in whom a concomitant reduction in BP is not demonstrated.",
"Eprosartan is a new nonphenyl angiotensin II receptor blocker, which has been approved for the treatment of hypertension. Although the drug has a relatively short plasma half-life of 5 to 9 h, clinical studies have suggested that its antihypertensive effect persists for 24 h.\n We assessed both the changes in 24-h and trough blood pressure (BP) (last 4 h of the ambulatory BP while the patient was awake) of eprosartan at doses of 600 and 1,200 mg once daily in a randomized, double-blind, placebo-controlled trial. Ambulatory BP was monitored at placebo baseline and after 8 weeks of double-blind therapy.\n Two hundred patients randomized in the study with 177 patients completing the trial. The 24-h change in BP from baseline was 0.2/0.1 +/- 1.4/1.0 mm Hg, -7.9/ -5.4 +/- 1.0 mm Hg (P < .0001), and -7.4/-5.0 +/- 0.9 mm Hg (P < .0001) in the placebo, 600-mg eprosartan, and 1,200-mg eprosartan groups, respectively. Changes in trough ambulatory BP showed significant reductions of -6.3/-4.1 +/- 1.6/1.1 mm Hg and -7.7/-5.5 +/- 1.5/1.0 mm Hg for 600 mg of eprosartan and 1,200 mg of eprosartan, respectively.\n These data demonstrate that eprosartan at doses of 600 or 1200 mg significantly reduced BP throughout an entire 24-h dosing period. There were no differences between the 600- and 1,200-mg dose; thus, 600 mg once daily should be the only dose used in the treatment of hypertension with eprosartan.",
"To determine the clinic and ambulatory blood pressure when the same dose of perindopril (4 mg) is administered in the morning (0900 h), or at night (2100 h), in particular, to determine whether the early morning blood pressure rise, the duration of effect and the pattern of response differed.\n Twenty male patients with diastolic blood pressure 95-110 mmHg when seated and 24 h mean ambulatory diastolic blood pressure > 85 mmHg after 4 weeks' placebo were allocated randomly to be administered 4 mg perindopril at 0900 h or at 2100 h. Clinic blood pressure (with the patient seated and erect) was measured 2 and 4 weeks after the therapy had been started and ambulatory blood pressure monitoring with a SpaceLabs device was performed for 26 h during week 4. The patients then crossed over to the other time of dosage and the measurements were repeated. The study was conducted from a hospital clinic.\n The clinic analysis concerned all 20 patients but the ambulatory analysis concerned 18 patients because the ambulatory blood pressure monitor data sets were inadequate for two patients. Compliance was high (97 +/- 3%), with a suggestion that it was better with the 0900 h dose. Clinic blood pressure (with the patient seated and erect) was lower under both regimes and the blood pressure with night-time administration of perindopril tended to be lower than that with daytime administration (P = 0.05-0.10). Twenty-four-hour mean, daytime and night-time means were lower with both doses than they were with placebo and did not differ. Both regimes reduced the early morning peak blood pressure rise and the effect tended to be greater with the 2100 h dose (P = 0.05-0.10). The 0900 h dose had an effect that persisted for > 24 h but the effect of the 2100 h dose had dissipated 18 h after the dose. There was no excessive night-time fall in blood pressure with the 2100 h dose. The trough : peak ratio with the 0900 h dose was 0.86 for systolic and 0.70 for diastolic blood pressure.\n The early morning blood pressure rise is reduced more when 4 mg perindopril is administered at 2100 h. However, the 2100 h dose regime does not reduce blood pressure over 24 h whereas 24 h control is achieved with the 0900 h dose. In clinical practice the 2100 h dose would have been titrated to the next dose range in more patients. This study indicates that the response profile obtained with an angiotensin converting enzyme inhibitor cannot be transformed from one dose time to another automatically and that chronobiology has important effects on a drug's action.",
"Many hypertensive patients require combination therapy to achieve target blood pressure (BP). beta-Blockers and dihydropyridine calcium channel blockers are effective as monotherapy in hypertensive patients and have complementary mechanisms for lowering BP.\n This multicenter, randomized, placebo-controlled, unbalanced factorial study included a 4- to 5-week single-blind placebo, 9-week, double-blind treatment as well as a 2-week double-blind, down-titration period. Patients (N = 1092) were randomized to one of 16 treatment groups: extended-release (ER) metoprolol succinate (25, 100, or 400 mg), ER felodipine (2.5, 10, or 20 mg), ER felodipine/ER metoprolol succinate (2.5/25, 2.5/100, 2.5/400, 10/25, 10/100, 10/400, 20/25, 20/100, or 20/400 mg), or placebo.\n At baseline, treatment groups were well balanced; mean sitting BP was 152.6/99.9 mm Hg. Monotherapy with ER metoprolol succinate induced dose-related reductions in sitting systolic/diastolic BP (DBP) (mean 8.1/7.7 to 9.7/11.1 mm Hg) as did ER felodipine (mean 7.7/7.7 to 14.0/11.8) and the combinations reflected additive effects (mean 13.8/11.0 to 19.8/15.2). The decline in the placebo group was 2.1/4.0 mm Hg. All combinations were more effective than their components (P < .05 for all but ER metoprolol succinate 25/ER felodipine 20). When compared with the highest doses of the individual agents (ER metoprolol succinate 400 mg; ER felodipine 20 mg), the low-dose combination ER metoprolol succinate 25/ER felodipine 2.5 was approximately as effective (differences in DBP <1 mm Hg). The most common adverse events leading to discontinuation were peripheral edema (4%), headache (2%), and fatigue (1%). Higher rates of peripheral edema and flushing were associated with high-dose ER felodipine, either alone or in combination.\n The antihypertensive effects of ER metoprolol succinate and ER felodipine are dose-related, and when given in combination, their BP-lowering effects are additive over a wide dose range. Low-dose combination therapy is comparable in effectiveness to high-dose monotherapy but is better tolerated.",
"Diabetes is the most common cause of renal failure in the United States, and data regarding the effects of aggressive blood pressure (BP) therapy in normotensive patients with type 2 diabetes are inadequate.\n A total of 129 type 2 diabetic patients with a BP of <140/80 to 90 mm Hg without overt albuminuria were randomized to either intensive BP control (diastolic BP goal 75 mm Hg) using an angiotensin II receptor blocker, valsartan, versus moderate BP control (diastolic BP 80 to 90 mm Hg with placebo initially) to evaluate the effect on the change in urinary albumin excretion (UAE) from baseline.\n The mean entrance BP was 126 +/- 8.8/84 +/- 2.4 mm Hg. The mean follow-up period was 1.9 +/- 1.0 years. During the follow-up period, the mean BP was 118 +/- 10.9/75 +/- 5.7 for the intensive v 124 10.9/80 6.5 mm Hg for the moderate BP groups (P < .001). No difference was observed in change in creatinine clearance or serum creatinine from baseline between the two groups. An analysis of covariance model for change in log (UAE + 1), adjusting for age, HBA(1c), duration of diabetes, baseline log (UAE + 1), sex, and ethnicity resulted in a significant treatment difference at 2 years (P = .007) with intensive BP control reducing log (UAE+1) compared with moderate BP control.\n Intensive BP control with valsartan to <120/80 mm Hg in normotensive patients with type 2 diabetes and normo- or microalbuminuria significantly decreased the progression of UAE and in some cases caused regression of UAE.",
"Tasosartan, a new, long-acting, nonpeptide angiotensin II receptor antagonist was evaluated in a randomized, double-blind, placebo-controlled, multicenter trial at 21 sites in the United States and Canada. After a 2-week, placebo washout qualification period, 278 patients (187 men/91 women) with a mean age of 53.4+/-9.5 years (range, 30 to 70 years) and a baseline sitting diastolic blood pressure (DBP) of 95 to 114 mm Hg were randomly assigned to receive placebo (n = 56), or 10 mg (n = 57), 30 mg (n = 55), 100 mg (n = 55), or 300 mg (n = 55) tasosartan for 4 weeks. The treatment period was followed by a 2-week washout period. Ambulatory blood pressure (BP) monitoring was performed at the end of the placebo washout period and after at least 4 weeks of double-blind treatment. Clinically significant placebo-adjusted differences in baseline sitting systolic blood pressure (SBP)/DBP were observed in the 10 mg (5/3 mm Hg), 30 mg (5/4 mm Hg), 100 mg (10/7 mm Hg) and 300 mg (10/7 mm Hg) dose groups (P < .05). A dose-response relationship (P < .001) was observed within 1 to 2 weeks of treatment initiation and was maintained throughout the double-blind period. Discontinuation of tasosartan therapy was not associated with rebound hypertension. Moreover, significant (P < .05) placebo-adjusted differences in ambulatory SBP/DBP and a significant dose-response relationship (P < .001) were observed with all tasosartan dosages during the 24-h, daytime, and nighttime periods. Placebo-adjusted trough-to-peak ratios ranged from 87% to 100% for ambulatory SBP and 64% to 81% for DBP. In general, no significant differences were observed between the tasosartan treatment groups and the placebo group in the incidence of adverse events. Headache incidence was significantly lower in the 300 mg dose group than the placebo group. In conclusion, tasosartan at dosages of 10, 30, 100, or 300 mg given once daily produced a significant and dose-related reduction in both clinic and ambulatory BP that was maintained over the 24-h period. Tasosartan was generally well tolerated.",
"To evaluate the effect on cardiac hemodynamic parameters of valsartan in patients with chronic stable congestive heart failure previously untreated with ACE inhibitors.\n After a 2 to 4 week run-in period, 116 adult outpatients were randomized to receive valsartan 40, 80 or 160 mg twice daily, the ACE inhibitor lisinopril 5/10 mg once daily, or placebo. At baseline and after 28 days of treatment, cardiac hemodynamic parameters were measured. Tolerability was assessed by adverse events and by any changes in systolic or diastolic blood pressure, body weight, heart rate, and routine laboratory parameters.\n For the 12 hour time point (trough), all doses of valsartan reduced mean pulmonary capillary wedge pressure (statistically significant for valsartan 40 mg and 160 mg), decreased systemic vascular resistance (statistically significant for all three valsartan doses and for lisinopril at peak and trough), and increased cardiac output (statistically significant for all three valsartan doses at peak, and for 80 and 160 mg at trough). There were no clinically relevant effects on any safety parameters.\n Valsartan has beneficial effects on cardiac hemodynamics, and is generally well tolerated in patients with congestive heart failure not taking ACE inhibitors.",
"Although the angiotensin receptor antagonist (ARB) shares the angiotensin-II-blocking activity with the angiotensin-converting enzyme inhibitor (ACE-I), pharmacological mechanisms of action of these agents differ. We evaluated the temporal profiles of action of ACE-I and ARB on urinary protein excretion and nitrate/nitrate (NO(x)) excretion in hypertensive (140 and/or 90 mmHg) patients with chronic renal disease (serum creatinine < 265 (range, 44-265) micromol/l or creatinine clearance > 30 (range, 30-121) ml/min). Patients with mild (<1 g/day; range, 0.4-1.0) and moderate proteinuria (>1 g/day; range, 1.1-6.9) were randomly assigned to ACE-I- and ARB-treated groups, and were treated with ACE-I (trandolapril or perindopril) or ARB(losartan or candesartan) for 48 weeks. In all groups, treatment with ACE-I or ARB decreased blood pressure to the same level, but had no effect on creatinine clearance. In patients with mild proteinuria, neither ACE-I nor ARB altered urinary protein excretion. In patients with moderate proteinuria, ACE-I caused 44 +/- 6% reduction in proteinuria (from 2.7 +/- 0.5 to 1.5 +/- 0.4 g/day, n = 14) at 12 weeks, and this beneficial effect persisted throughout the protocol (48 weeks, 1.2 +/- 0.2 g/day). In contrast, ARB did not produce a significant decrease in proteinuria at 12 weeks (23 +/- 8%, n = 13), but a 41 +/- 6% reduction in proteinuria was observed at 48 weeks. Similarly, although early (12 weeks) increases in urinary NO(x) excretion were observed with ACE-I (from 257 +/- 70 to 1111 +/- 160 micromol/day) and ARB (from 280 +/- 82 to 723 +/- 86 micromol/day), the ARB-induced increase in NO(x) excretion was smaller than that by ACE-I (P < 0.05). In conclusion, although both ACE-I and ARB reduce blood pressure similarly, the effect of these agents on proteinuria differs in chronic renal disease with moderate proteinuria. Relatively early onset of the proteinuria-reducing effect was observed with ACE-I, which paralleled the increase in urinary NO(x) excretion. Conversely, ARB decreased proteinuria and increased urinary NO(x) excretion gradually. These time course-dependent changes in proteinuria and urinary NO(x) may reflect the pharmacological property of ACE-I and ARB, with regard to the action on bradykinin.",
"We assessed blood pressure (BP) and heart rate (HR) responses in a double-blind, randomized study comparing cilazapril, a long-acting, nonsulfhydryl-group converting enzyme inhibitor, with placebo in 18 patients with mild to moderate (sitting diastolic BP, 95 to 114 mm Hg) essential hypertension. The BP and HR parameters were evaluated at rest (casual, 24 hours after administration), during treadmill exercise testing (Bruce protocol), and with 24-hour noninvasive ambulatory BP monitoring. These assessments were made after a 4-week drug washout period and after 8 to 12 weeks of therapy. After 8 weeks of therapy with cilazapril (mean dose 3.6 +/- 0.9 mg/day), casual BP decreased 19/11 mm Hg (p less than 0.01), whereas placebo lowered BP by 4/5 mm Hg (difference not significant) compared with the baseline period. The casual HR was modestly (7 beats/min) but significantly (p less than 0.05) lowered by cilazapril monotherapy. Exercise BP was reduced by cilazapril (reduction at peak HR, 23/11 +/- 10/5 mm Hg; p less than 0.05), and exercise HR was unchanged. Compared with baseline, the duration of exercise was improved with cilazapril but not with placebo (1.0 minute vs -0.2 minute; p less than 0.05). Twenty-four-hour mean, awake, and sleep BPs were reduced with cilazapril with the most impressive reduction occurring during the awake period (19/12 mm Hg; p less than 0.01). These data demonstrate that cilazapril lowers casual, exercise, and ambulatory BP with a modest but significant improvement in exercise time. Thus cilazapril may be particularly effective in the physically active hypertensive patient.",
"Weight loss, sodium reduction, increased physical activity, and limited alcohol intake are established recommendations that reduce blood pressure (BP). The Dietary Approaches to Stop Hypertension (DASH) diet also lowers BP. To date, no trial has evaluated the effects of simultaneously implementing these lifestyle recommendations.\n To determine the effect on BP of 2 multicomponent, behavioral interventions.\n Randomized trial with enrollment at 4 clinical centers (January 2000-June 2001) among 810 adults (mean [SD] age, 50 [8.9] years; 62% women; 34% African American) with above-optimal BP, including stage 1 hypertension (120-159 mm Hg systolic and 80-95 mm Hg diastolic), and who were not taking antihypertensive medications.\n Participants were randomized to one of 3 intervention groups: (1) \"established,\" a behavioral intervention that implemented established recommendations (n = 268); (2) \"established plus DASH,\"which also implemented the DASH diet (n = 269); and (3) an \"advice only\" comparison group (n = 273).\n Blood pressure measurement and hypertension status at 6 months.\n Both behavioral interventions significantly reduced weight, improved fitness, and lowered sodium intake. The established plus DASH intervention also increased fruit, vegetable, and dairy intake. Across the groups, gradients in BP and hypertensive status were evident. After subtracting change in advice only, the mean net reduction in systolic BP was 3.7 mm Hg (P<.001) in the established group and 4.3 mm Hg (P<.001) in the established plus DASH group; the systolic BP difference between the established and established plus DASH groups was 0.6 mm Hg (P =.43). Compared with the baseline hypertension prevalence of 38%, the prevalence at 6 months was 26% in the advice only group, 17% in the established group (P =.01 compared with the advice only group), and 12% in the established plus DASH group (P<.001 compared with the advice only group; P =.12 compared with the established group). The prevalence of optimal BP (<120 mm Hg systolic and <80 mm Hg diastolic) was 19% in the advice only group, 30% in the established group (P =.005 compared with the advice only group), and 35% in the established plus DASH group (P<.001 compared with the advice only group; P =.24 compared with the established group).\n Individuals with above-optimal BP, including stage 1 hypertension, can make multiple lifestyle changes that lower BP and reduce their cardiovascular disease risk.",
"This double-blind, placebo-controlled, dose-ranging study recruited 170 patients with mild-to-moderate hypertension from nine centers. After a 4-week, single-blind, placebo run-in phase, patients were randomized in a double-blind fashion to four parallel groups that received either placebo or 0.5, 1, or 2 mg trandolapril for 4 weeks. Treatment was administered as a once-daily dose in the morning and blood pressure was measured 24 h after drug intake. The primary criterion of efficacy was a decrease in supine diastolic blood pressure. At the end of the study, the lowest dose of trandolapril that consistently produced a significant difference from placebo in reducing blood pressure was 1 mg (-6.6 mm Hg for supine diastolic blood pressure). It was effective from around 2 weeks onward; the 2-mg dose differed significantly from placebo from around 1 week onward. At the end of the study, the 1- and 2-mg doses were equally effective. The lowest dose tested, 0.5 mg, showed some evidence of an effect on systolic blood pressure and may well prove to be a useful dose in patients who are highly sensitive to the effect of ACE inhibition. Tolerance throughout the study was good for all doses tested.",
"Our aim was to compare the effect of lacidipine and chlorthalidone on cardiovascular outcome as a primary parameter and blood pressure as a secondary in elderly patients with isolated systolic hypertension in a prospective study with an open design.\n 1882 males and females outpatients > or = 60 years were randomly assigned to the administration of chlorthalidone 12.5 mg o.d. or lacidipine 4 mg o.d. Patients were recruited if sitting systolic blood pressure was > or = 160 mmHg with a diastolic blood pressure equal or lower than 95 mmHg. Primary endpoint was a composite of cardiovascular and cerebrovascular events.\n At randomization mean systolic blood pressure was 178.1 mmHg in the lacidipine and 178.2 mmHg in the chlorthalidone group, the corresponding mean diastolic values being 86.9 and 86.8 mmHg. In both lacidipine and chlorthalidone groups treatment caused a significant (p < 0.001) and marked systolic blood pressure reduction which was maintained throughout the treatment period with a significant (p < 0.001) and steady although less marked reduction in diastolic blood pressure as well. At the end of treatment period (median 32 months), the reduction was 36.8/8.1 mmHg (systolic/diastolic) in the chlorthalidone and 38.4/7.9 mmHg in the lacidipine group, the final on treatment blood pressures being 142.0/79.2 and 143.2/79.5 mmHg, respectively. Treatments were similarly effective in males and females and in age groups between 60 and 69 years (n = 763), 70 and 79 years (n = 744) and > or = 80 years (n = 375). Similar reductions were obtained in a subgroup of patients (n = 209) followed in double-blind fashion for 1 year. The overall incidence of the primary endpoints was 9.3% with no significant between-group difference. Total mortality was also similar between groups.\n In elderly patients with isolated systolic hypertension, administration of lacidipine or chlorthalidone markedly reduced systolic blood pressure with no difference in the incidence of cardiovascular events and total mortality.",
"This multicentre, double-blind, parallel-group, placebo-controlled study compared the antihypertensive effects of equal doses of two long-acting angiotensin converting enzyme (ACE) inhibitors. After a two-week, placebo run-in phase, 110 patients with mild to moderate hypertension were randomised to receive 10 mg lisinopril or enalapril, or placebo for 4 weeks. Office BPs were measured at regular intervals throughout the study. Twenty-four hour ambulatory blood pressure (ABP) was measured at baseline and after the first and final doses of study drug. Serum ACE activity and aldosterone were obtained concomitantly with each ABP monitoring. Office BP differences from placebo reached (P less than 0.05) or approached (P less than 0.10) statistical significance at all observations for the lisinopril group but were not significant for any observation in the enalapril group and approached significance on two occasions. After four weeks of treatment, ABP analysis revealed that the lisinopril and enalapril groups, when compared with placebo, had similar and significant systolic and diastolic AUC reductions (P less than 0.01) from baseline over the 24 h dosing interval. During the second half of the dosing interval, 13-24 h post drug administration, the lisinopril group was significantly different from placebo (systolic BP, P = 0.002; diastolic BP, P = 0.005) while the enalapril group was not. Both drugs were well tolerated. The results indicate that monotherapy with 10 mg of lisinopril is as effective as with 10 mg of enalapril, and that ABP monitoring is useful in more precisely depicting the clinical effect of the known pharmacokinetic properties of these two agents.",
"This study was undertaken to test the hypothesis that, given equal arterial pressure reductions, the combination of an angiotensin converting enzyme (ACE) inhibitor and calcium antagonist slows declines in renal function and yields greater reductions in albuminuria over either agent alone. This hypothesis was evaluated in four groups of hypertensive, non-insulin dependent, diabetic subjects with renal insufficiency (N = 30). Renal hemodynamics, albuminuria and metabolic parameters were evaluated for a period of one year. Subjects were all placed on a 90 mEq sodium, 0.8 g/kg protein, 1500 calorie American Diabetes Association diet for the entire length of the study. Subjects were followed for two weeks off antihypertensive medications and were subsequently randomized to either lisinopril, alone (group I), sustained release verapamil, alone (group II), reduced doses of both lisinopril and sustained release verapamil (group III), and hydrochlorothiazide with guanfacine (group IV). At the end of one year group III had the greatest reduction in albuminuria (78 +/- 7%, group III vs. 59% +/- 4, group I: P less than 0.05). In addition, the decline in glomerular filtration rate (GFR) was the lowest in this group (0.28 +/- 0.07, group III vs. 0.69 +/- 0.12, group I; P less than 0.05) although there was no significant difference between groups II and IV. The highest side effect profiles were noted in group IV, the least in group III. The greatest reductions in renal hemodynamics occurred in all groups within the first month; however, striking differences between groups were noted (7.4 +/- 2%, group I vs. 1.4 +/- 2%, group III; P less than 0.05). We conclude that the combination of reduced doses of an ACE inhibitor and calcium antagonist attenuate both albuminuria and the rate of decline in glomerular filtration rate. Furthermore, the combination of these classes of agents appear to yield the lowest side effect profile over either agent alone. Lastly, high doses of ACE inhibition alone may be detrimental to renal function in late stage diabetics with renal insufficiency.",
"In a double-blind, randomized, multicenter trial, we compared the efficacy and safety of the fixed combination of 5 mg ramipril and 6 mg piretanide and the respective component monotherapies in hypertensive patients [supine diastolic blood pressure (DBP) 100-114 mm Hg]. After a single-blind run-in period on placebo, 611 patients were randomized to ramipril (n = 209), piretanide (n = 201), or the combination therapy (n = 201). At randomization, the three groups had the same characteristics (51% men, age 55 +/- 10 years, BP 165 +/- 18/104 +/- 6 mm Hg). At 4 weeks, BP decreased more with combined therapy than with monotherapy. As compared with piretanide monotherapy, the gain in the antihypertensive effect in the supine position averaged 2.1 mm Hg [90% confidence interval (CI) -0.8-5.0 mm Hg; p = 0.07] systolic BP (SBP) and 1.9 mm Hg (CI 0.3-3.5 mm Hg, p = 0.02) DBP and, as compared with ramipril monotherapy, these differences were 4.2 mm Hg (CI 1.3-7.0 mm Hg, p = 0.008) and 2.0 mm Hg (CI 0.5-3.6 mm Hg, p = 0.009). The incidence of adverse events (AE) and the changes in biochemical measurements were similar in the three treatment groups with the exception of spontaneously reported polyuria and serum uric acid concentration. Polyuria was reported more frequently (p < 0.001) with piretanide therapy (n = 23) and combined therapy (n = 19) than with ramipril therapy (n = 1).(ABSTRACT TRUNCATED AT 250 WORDS)",
"The time to peak antihypertensive effect and the trough-to-peak ratio were determined in 64 Caucasian patients (19 men, 45 women) with mild to moderate hypertension [supine diastolic blood pressure (DBP) 95 to 115 mmHg]. They received placebo or fosinopril 10, 20, or 40 mg once daily for 4 weeks. The study consisted of a 4-week placebo lead-in, 4 weeks' double-blind treatment, and a 1-week placebo washout period. Vital signs were determined biweekly before dosing, and blood pressures were measured every 1 to 2 h during two 27-h periods at the beginning and end of treatment. After the first and last doses of all three regimens, the peak effect on blood pressure occurred 5 to 7 h after all three dosages. Neither peak nor trough blood pressure changes showed a clear dose-response relationship. Trough to peak ratios for the first dose, corrected for placebo effects, were 79% for fosinopril 10 mg, 48% for fosinopril 20 mg, and 74% for fosinopril 40 mg, and the trough-to-peak ratios for the last dose were 41% for fosinopril 10 mg, 32% for fosinopril 20 mg, and 44% for fosinopril 40 mg. In the 38 responders among the 48 patients receiving fosinopril (supine DBP decrease of at least 5 mmHg at 24 h postdose), trough-to-peak ratios ranged from 50 to 81%, and the range indicates that fosinopril is efficacious when administered once daily. Adverse effects were mild to moderate, and no patient discontinued treatment. Changes in the laboratory test results, electrocardiograms, or the results of physical examinations were unremarkable.(ABSTRACT TRUNCATED AT 250 WORDS)",
"To study the effects of ACE-i in type 1 diabetic patients with early microalbuminuria with regard to: i) UAE, ii) 24 h AMBP, including the effect on diurnal BP variation, and iii) renal haemodynamics.\n 58 patients with urinary albumin excretion (UAE) between 20-70 microg/min were treated for two years with either the ACE inhibitor (ACE-i) lisinopril (20 mg od) or placebo in two randomised placebo controlled double blind studies. In a subgroup of patients (n=22) we performed 24 h ambulatory blood pressure measurements (AMBP) and renal function tests (constant infusion technique).\n i) Changes in UAE over the two years were significantly different (p<0.01) in the two groups with final UAE in the lisinopril group of 19.1 microg/min x/divide 2.5 (geometric mean x/divide tolerance factor) and 44.1 microg/min x/divide 2.8 in the placebo group. In the lisinopril group 20 patients (60.6%) reversed to normoalbuminuria compared to 6 patients (24%) in the placebo group (p<0.02). ii) Clinical BP measurements revealed no differences between groups, but by AMBP significant reductions were detectable in the lisinopril group, primarily in night AMBP (systolic/diastolic: - 6.9 +/- 8.6/- 6.0 +/- 5.3 mmHg, p<0.01) as opposed to increases in the placebo group (3.1 +/- 9.3/1.9 +/- 7.3 mmHg). iii) Changes in UAE and changes in filtration fraction (FF) were positively correlated in the intervention group (r=0.9, p<0.01), i.e. the patients who showed the greatest fall in UAE were the ones with the greatest fall in FF.\n ACE-i treatment in patients with low-grade microalbuminuria reduces 24 h AMBP without attenuating diurnal blood pressure variation, reduces UAE significantly, with changes in UAE being strongly associated with changes in FF. Furthermore, compared to placebo, ACE-i reverses micro- to normoalbuminuria in a significant fraction of patients.",
"To investigate the concept of initiating therapy with low doses of a calcium antagonist and an ACE inhibitor, a fixed combination of isradipine 2.5 mg plus the ACE inhibitor spirapril 3 mg was compared with its components, with the full-dose monotherapies (isradipine 5 mg or spirapril 6 mg), and with placebo. After a 2-week wash out phase in pretreated patients and a subsequent 2-week placebo period, 405 patients with a diastolic blood pressure (DBP) between 100 and 114 mmHg were randomly allocated to 12-week once-daily double-blind treatment in one of the six treatment arms. In patients whose blood pressure was not normalized (defined as DBP< or =90 mmHg) after 6 weeks of treatment, the dosage of either medication was doubled or, in the placebo group, was switched to the fixed combination. After week 6, the mean reductions from baseline in sitting systolic/diastolic blood pressure 24 hours after dosing (trough) for the fixed combination or the monotherapies isradipine 5 mg, isradipine 2.5 mg, spirapril 6 mg, spirapril 3 mg, and placebo were 10.4/8.7, 10.0/9.4, 6.5/6.7, 10.0/8.3, 7.0/5.8, and 2.2/4.7 mmHg, respectively. The blood pressure changes obtained with the low-dose fixed combination were essentially identical to those observed with the full-dose monotherapies, thus showing an additive effect of low-dose isradipine and spirapril. In terms of tolerability, the lowest rate of any adverse events was found in the combination group. In this group, typical adverse events of calcium antagonists, such as headache, flushing, ankle edema, or palpitations, were observed only in 5%, 2%, 1%, and 0%, respectively, dry cough, considered typical for ACE inhibitors, was observed in only 1% of the combination group. In conclusion, the low-dose components isradipine 2.5 mg and spirapril 3 mg were shown to have an additive effect when combined, exerting a blood pressure-lowering effect comparable with the full doses and a trend to a better tolerability profile in comparison with the standard doses. Thus, low-dose combination therapy with these drugs appears to be a rational alternative to conventional monotherapy in the first-line treatment of hypertension.",
"In chronic nephropathies, inhibition of angiotensin-converting enzyme (ACE) is renoprotective, but can further renoprotection be achieved by reduction of blood pressure to lower than usual targets? We aimed to assess the effect of intensified versus conventional blood-pressure control on progression to end-stage renal disease.\n We undertook a multicentre, randomised controlled trial of patients with non-diabetic proteinuric nephropathies receiving background treatment with the ACE inhibitor ramipril (2.5-5 mg/day). We randomly assigned participants either conventional (diastolic <90 mm Hg; n=169) or intensified (systolic/diastolic <130/80 mm Hg; n=169) blood-pressure control. To achieve the intensified blood-pressure level, patients received add-on therapy with the dihydropyridine calcium-channel blocker felodipine (5-10 mg/day). The primary outcome measure was time to end-stage renal disease over 36 months' follow-up, and analysis was by intention to treat.\n Of 338 patients who were randomised, three (two assigned intensified and one allocated conventional blood-pressure control) never took study drugs and they were excluded. Over a median follow-up of 19 months (IQR 12-35), 38/167 (23%) patients assigned to intensified blood-pressure control and 34/168 (20%) allocated conventional control progressed to end-stage renal disease (hazard ratio 1.00 [95% CI 0.61-1.64]; p=0.99).\n In patients with non-diabetic proteinuric nephropathies receiving background ACE-inhibitor therapy, no additional benefit from further blood-pressure reduction by felodipine could be shown.",
"Angiotensin-converting-enzyme (ACE) inhibitors improve outcome of patients with chronic heart failure (CHF). A substantial proportion of patients, however, experience no benefit from ACE inhibitors because of previous intolerance. We aimed to find out whether candesartan, an angiotensin-receptor blocker, could improve outcome in such patients not taking an ACE inhibitor.\n Between March, 1999, and March, 2001, we enrolled 2028 patients with symptomatic heart failure and left-ventricular ejection fraction 40% or less who were not receiving ACE inhibitors because of previous intolerance. Patients were randomly assigned candesartan (target dose 32 mg once daily) or matching placebo. The primary outcome of the study was the composite of cardiovascular death or hospital admission for CHF. Analysis was by intention to treat.\n The most common manifestation of ACE-inhibitor intolerance was cough (72%), followed by symptomatic hypotension (13%) and renal dysfunction (12%). During a median follow-up of 33.7 months, 334 (33%) of 1013 patients in the candesartan group and 406 (40%) of 1015 in the placebo group had cardiovascular death or hospital admission for CHF (unadjusted hazard ratio 0.77 [95% CI 0.67-0.89], p=0.0004; covariate adjusted 0.70 [0.60-0.81], p<0.0001). Each component of the primary outcome was reduced, as was the total number of hospital admissions for CHF. Study-drug discontinuation rates were similar in the candesartan (30%) and placebo (29%) groups.\n Candesartan was generally well tolerated and reduced cardiovascular mortality and morbidity in patients with symptomatic chronic heart failure and intolerance to ACE inhibitors.",
"There is much uncertainty about the effects of early lowering of elevated blood pressure (BP) after acute intracerebral haemorrhage (ICH). Our aim was to assess the safety and efficiency of this treatment, as a run-in phase to a larger trial.\n Patients who had acute spontaneous ICH diagnosed by CT within 6 h of onset, elevated systolic BP (150-220 mm Hg), and no definite indication or contraindication to treatment were randomly assigned to early intensive lowering of BP (target systolic BP 140 mm Hg; n=203) or standard guideline-based management of BP (target systolic BP 180 mm Hg; n=201). The primary efficacy endpoint was proportional change in haematoma volume at 24 h; secondary efficacy outcomes included other measurements of haematoma volume. Safety and clinical outcomes were assessed for up to 90 days. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00226096.\n Baseline characteristics of patients were similar between groups, but mean haematoma volumes were smaller in the guideline group (12.7 mL, SD 11.6) than in the intensive group (14.2 mL, SD 14.5). From randomisation to 1 h, mean systolic BP was 153 mm Hg in the intensive group and 167 mm Hg in the guideline group (difference 13.3 mm Hg, 95% CI 8.9-17.6 mm Hg; p<0.0001); from 1 h to 24 h, BP was 146 mm Hg in the intensive group and 157 mm Hg in the guideline group (10.8 mm Hg, 95% CI 7.7-13.9 mm Hg; p<0.0001). Mean proportional haematoma growth was 36.3% in the guideline group and 13.7% in the intensive group (difference 22.6%, 95% CI 0.6-44.5%; p=0.04) at 24 h. After adjustment for initial haematoma volume and time from onset to CT, median haematoma growth differed between the groups with p=0.06; the absolute difference in volume between groups was 1.7 mL (95% CI -0.5 to 3.9, p=0.13). Relative risk of haematoma growth >or=33% or >or=12.5 mL was 36% lower (95% CI 0-59%, p=0.05) in the intensive group than in the guideline group. The absolute risk reduction was 8% (95% CI -1.0 to 17%, p=0.05). Intensive BP-lowering treatment did not alter the risks of adverse events or secondary clinical outcomes at 90 days.\n Early intensive BP-lowering treatment is clinically feasible, well tolerated, and seems to reduce haematoma growth in ICH. A large randomised trial is needed to define the effects on clinical outcomes across a broad range of patients with ICH.\n National Health and Medical Research Council of Australia.",
"Angiotensin-converting enzyme (ACE) inhibitors have been shown to slow the progression of chronic renal failure. However, the value of ACE inhibitors for the treatment of hypertension in renal allograft recipients has not been established. ACE inhibitors dilate the efferent glomerular arteriole, an effect that may aggravate the decrease in glomerular filtration rate resulting from cyclosporine-induced vasoconstriction at the afferent glomerular arteriole. Therefore, the goal of this double-blind, randomized study was to compare the antihypertensive and renal effects of the ACE inhibitor quinapril with those of the beta-blocker atenolol in renal allograft recipients in whom hypertension developed 6 to 12 weeks after transplantation. All patients received cyclosporine as an immunosuppressant and had stable graft function (serum creatinine concentration, <220 micromol/L) at entry into the study. Twenty-nine patients who received quinapril (daily dose titrated between 2.5 and 20 mg) and 30 patients who received atenolol (daily dose titrated between 12.5 and 100 mg) completed the 24-month study. The two groups did not differ in age, sex ratio, height, and weight before entry into the study. Quinapril decreased diastolic blood pressure from 96+/-1 to 84+/-1 mm Hg (average throughout treatment period), and atenolol decreased diastolic blood pressure from 96+/-1 to 83+/-1 mm Hg. The serum creatinine concentration did not change significantly in either group after 24 months (129+/-8 micromol/L at entry and 148+/-19 micromol/L after 24 months in the quinapril group and 131+/-6 micromol/L at entry and 152+/-15 micromol/L after 24 months in the atenolol group; P=NS for both groups). After 24 months, the change in urinary albumin excretion from baseline was -10+/-15 mg/d in the quinapril group and 52+/-32 mg/d in the atenolol group (P=0.03). These results show that quinapril and atenolol are effective antihypertensive drugs when used after renal transplantation. Moreover, compared with atenolol, quinapril has no adverse effects on graft function. The relative reduction in albuminuria observed with quinapril as compared with atenolol could indicate a beneficial effect of quinapril on long-term graft function.",
"Recent studies utilizing converting enzyme inhibitors (CEI) in diabetic rats document reductions in both renal hypertrophy and albuminuria. Four separate clinical studies in normotensive patients with diabetes demonstrate reduction of microalbuminuria with CEIs independent of blood pressure reduction. The present pilot study examines the results of reducing an elevated glomerular filtration rate on changes in renal size and microalbuminuria in normotensive, hyperfiltering insulin-dependent diabetic (IDDM) patients. Fifteen IDDM patients were randomized to either placebo or the CEI, lisinopril. Dosage of lisinopril was titrated over 3 months to reduce glomerular filtration rate (GFR) to < or = 2.33 mL/sec. Evaluation at 18 months demonstrated the lisinopril group had a marked reduction in renal size (16.9 +/- 1.1, baseline versus 12.8 +/- 0.9 cm, 18 months; p < 0.05) and microalbuminuria (92 +/- 11 micrograms/min, baseline versus 23 +/- 26 micrograms/min, 18 months; p < 0.05). No change in renal size was noted in the placebo group (15.4 +/- 0.8, baseline versus 14.9 +/- 0.7 cm, 18 months; NS) and albuminuria increased (118 +/- 15 micrograms/min, baseline versus 293 +/- 32 micrograms/min, 18 months; p < 0.05). Mean arterial pressure at 18 months was significantly lower in the lisinopril group compared to placebo (102 +/- 4, placebo versus 87 +/- 6 mm Hg, CEI, p < 0.05). This study supports previous animal studies that document reductions in both microalbuminuria and renal size by a CEI. The overall impact of these findings on preservation of renal function cannot be assessed, however, in this short-term study.",
"The objectives of this double-blind, multicenter, randomized, parallel-arm, placebo-controlled study were to evaluate the dose-related efficacy, tolerability, and safety of candesartan cilexetil, a potent, AT1 selective, long-acting angiotensin II receptor blocker, in 365 adult patients with systemic hypertension and mean sitting diastolic blood pressure (BP) of 95 to 114 mm Hg. Patients received either placebo or candesartan cilexetil 2, 4, 8, 16, or 32 mg once daily for 8 weeks. All doses of candesartan cilexetil reduced trough (24 hours after treatment) sitting diastolic and systolic BP significantly compared with placebo (p < 0.005). A significant (p < or = 0.0001) dose response was evident, with greater decreases in BP at higher doses. Mean changes in BP were -10.7/-7.8 mm Hg and -12.6/-10.2 mm Hg in the 16- and 32-mg groups, respectively, versus -0.3/-2.6 mm Hg in the placebo group. The 16- and 32-mg doses were consistently significantly superior to placebo in antihypertensive effect with regard to all BP measurements, including peak (6 hours after treatment), trough, sitting, and standing measurements of diastolic and systolic BP. Responder rates (trough sitting diastolic BP < 90 or > or = 10 mm Hg BP decrease) were 54% and 64% for the 16- and 32-mg groups, respectively. Tolerability and safety profiles were similar to placebo at all doses. In conclusion, candesartan cilexetil administered once daily effectively reduces BP in a dose-related manner while maintaining safety and tolerability; doses of 16 and 32 mg are most effective for treatment of hypertension.",
"Patients with reduced renal function are at increased risk for adverse cardiovascular outcomes. In the post-myocardial infarction setting, angiotensin-converting enzyme (ACE) inhibitors have been shown to be as effective in patients with impaired renal function as in those with preserved renal function.\n We assessed the relation between renal function and outcomes, the influence of ACE inhibition on this relation, and whether renal function modifies the effectiveness of ACE inhibition in patients with stable coronary artery disease and preserved systolic function enrolled in the Prevention of Events with ACE inhibition trial (PEACE). Patients (n=8290) were randomly assigned to receive trandolapril (target, 4 mg/d) or placebo. Clinical creatinine measures were available for 8280 patients before randomization. The estimated glomerular filtration rate (eGFR) was calculated with the 4-point Modification of Diet in Renal Disease equation. Renal function was related to outcomes, and the influence of ACE-inhibitor therapy was assessed with formal interaction modeling. The mean eGFR in PEACE was 77.6+/-19.4, and 1355 (16.3%) patients had reduced renal function (eGFR <60 mg.mL(-1).1.73 m(-2)). We observed a significant interaction between eGFR and treatment group with respect to cardiovascular and all-cause mortality (P=0.02). Trandolapril was associated with a reduction in total mortality in patients with reduced renal function (adjusted HR, 0.73; 95% CI, 0.54 to 1.00) but not in patients with preserved renal function (adjusted HR, 0.94; 95% CI, 0.78 to 1.13).\n Although trandolapril did not improve survival in the overall PEACE cohort, in which mean eGFR was relatively high, trandolapril reduced mortality in patients with reduced eGFR. These data suggest that reduced renal function may define a subset of patients most likely to benefit from ACE-inhibitor therapy for cardiovascular protection.",
"The primary objectives of this double-blind study were to compare the antihypertensive efficacy and tolerability of irbesartan and losartan, two angiotensin II (AT1 subtype) receptor antagonists with different pharmacokinetic profiles in patients with mild-to-moderate hypertension. Both drugs are approved for once-daily use (although losartan may also be prescribed twice-daily). After a placebo lead-in, 567 patients were randomized (1:1:1:1) to once-daily therapy with placebo, 100 mg losartan, 150 mg irbesartan, or 300 mg irbesartan for 8 weeks. Treatment groups had comparable demographic and baseline characteristics. After 8 weeks of treatment, reductions from baseline in trough seated diastolic blood pressure (SeDBP) and trough seated systolic blood pressure (SeSBP) with 300 mg irbesartan were greater than with 100 mg losartan (P < .01 for both comparisons), by 3.0 and 5.1 mm Hg, respectively; larger reductions were also demonstrated at weeks 1 and 4 (P < .01 and P = .017, respectively, for SeDBP). Throughout the study, the antihypertensive effect of 150 mg irbesartan did not differ significantly from that of 100 mg losartan. All therapies were well tolerated. The 300 mg dose of irbesartan was associated with the lowest incidence of adverse events (AE) and discontinuations because of AE. This study demonstrates that the maximally effective once-daily doses of two different AT1 receptor antagonists may result in clinically significant differences in blood pressure reductions, and therefore highlights the potential importance of the pharmacokinetic and pharmacodynamic differences between these two members of this class.",
"The objective of this study was to evaluate the effects of celiprolol, a new beta-blocking drug, on the clinical condition and pulmonary function of hypertensive patients with reversible bronchial obstruction. Celiprolol was compared with chlorthalidone, an antihypertensive drug without known effect on bronchial tone. The study consisted of a 4-week placebo run-in period and a 12-week titration period in which the dose of both drugs was increased at 4-week intervals if blood pressure was not reduced adequately. The doses of celiprolol were 200, 400, or 600 mg once daily; those for chlorthalidone 12.5, 25, or 37.5 mg once daily. Entry criteria were a diastolic blood pressure between 90 and 115 mg Hg, and FEV-1 between 40% and 80% of predicted value, increasing by 15% or more after salbutamol, and a need for occasional bronchodilator therapy. Prophylactic medication for asthma was given in constant dosage for a month before the study and throughout the study. Preliminary results on 66 patients demonstrate that neither drug had a clinically significant effect on FEV-1, FEF 25-75, or FVC. Clinical variables were not significantly changed by either drug: the average monthly asthma attacks fell from 18 to 13 with celiprolol and from 11 to 7 with chlorthalidone. FEF was reduced by more than 50% in two patients on celiprolol and three on chlorthalidone. Monthly asthma attacks increased by more than 100% in five patients on celiprolol and four on chlorthalidone. Thus, preliminary results are unable to demonstrate adverse effects from celiprolol in patients with asthma and hypertension.",
"This multicenter international trial recruited 205 patients from 16 investigators. After a 4-week, single-blind placebo run-in, patients were randomized to receive 16 weeks of trandolapril 2 mg/day (68 patients), hydrochlorothiazide (HCTZ) 25 mg/day (68 patients), or the combination (69 patients). Morning predosing supine diastolic blood pressure (DBP) was the primary efficacy measurement. Intention-to-treat analysis showed significant decreases in all three groups in mean (+/- SEM) supine DBP throughout the study, with no significant differences at week 16 between trandolapril (-10.6 +/- 1.3 mm Hg) and HCTZ (-10.9 +/- 1.3 mm Hg). The combination gave a significantly greater reduction than either drug alone (-15.1 +/- 1.13 mm Hg). Blood pressure was normalized in the combination group in 67% of patients, a significantly higher proportion than either trandolapril (63%) or HCTZ (60%; p = 0.04). Each treatment was well tolerated. The incidence of adverse events was similar in all three groups. Trandolapril 2 mg once daily is an effective antihypertensive agent, comparable to HCTZ. Furthermore, the combination of the two drugs was shown to enhance the antihypertensive effect of the two compounds alone.",
"Although nonpharmacologic interventions are widely recommended in the therapy of high blood pressure in older adults, surprisingly little data exist to confirm the efficacy of these interventions in older persons.\n We conducted a randomized, controlled clinical trial in persons aged 60 to 85 years with a diastolic blood pressure of 85 to 100 mm Hg. The experimental arm was a nonpharmacologic intervention combining weight reduction, sodium restriction, and increased physical activity. The nonpharmacologic intervention consisted of eight weekly group and two individual sessions during the intensive phase, followed by four monthly group sessions during the maintenance phase. The control group received no treatment during the study. Blood pressure was assessed by certified technicians (blinded to group assignment) using random zero sphygmomanometers.\n Of 56 participants randomized, 47 completed the entire 6-month trial (21 in the intervention group and 26 in the control group). Attendance at the intervention sessions was excellent. The intervention group lost more weight (-2.1 kg) over 6 months than the control group (+0.3 kg). Trends for decreasing 24-hour urine sodium excretion in both the intervention and control groups, with greater trend in the intervention group, were not statistically significant. The intervention group experienced more reduction in systolic and diastolic blood pressure than did the control group (mean differences between groups at 6 months, 4.2/4.9 mm Hg, respectively).\n Our data indicate that a nonpharmacologic intervention will lower systolic and diastolic blood pressure levels in older people with borderline or mild elevations of diastolic blood pressure.",
"Some retrospective studies have suggested a beneficial influence of angiotensin-converting enzyme (ACE) inhibitors on the progression of IgA nephropathy (IgAN), but prospective and controlled studies demonstrating this effect are lacking. Forty-four patients with biopsy-proven IgAN, proteinuria > or = 0.5 g/d, and serum creatinine (SCr) < or = 1.5 mg/dl were randomly assigned either to receive enalapril (n = 23) or to a control group (n = 21) in whom BP was controlled with antihypertensives other than ACE inhibitors. Primary outcome was renal survival estimated by a 50% increase in baseline SCr. Secondary outcomes were the presence of a SCr > 1.5 mg/dl at the last visit and the evolution of proteinuria. Baseline clinical findings were similar at baseline between enalapril-treated and control group, and there were no differences in BP control during follow-up. Mean follow-up was 78 +/- 37 mo in the enalapril group and 74 +/- 36 mo in the control group. Three patients (13%) in the enalapril group and 12 (57%) in the control group reached the primary end point (P < 0.05). Kaplan-Meier renal survival was significantly better in enalapril group than in control group: 100% versus 70% after 4 yr and 92% versus 55% after 7 yr (P < 0.05). Three patients in the enalapril group (13%) and 11 (52%) in the control group showed SCr > 1.5 mg/dl at the last visit (P < 0.05). Proteinuria significantly decreased in the enalapril group, whereas it tended to increase in the control group (P < 0.001 between groups). In conclusion, ACE inhibitors significantly improve renal survival in proteinuric IgAN with normal or moderately reduced renal function.",
"Ninety four patients with mild hypertension (average supine diastolic blood pressure (phase V) 95-110 mm Hg) were allocated at random to receive restriction of dietary sodium (maximum allowed 70 mmol(mEq)/24 h) or a normal diet. In addition, they received in random order 25 mg chlorthalidone, 200 mg metoprolol (slow release), and a fixed combination of these two drugs. Each drug treatment was given for four weeks and alternated with four weeks of placebo. Forty four patients were allocated to sodium restriction (group 1) and 50 to normal diet (group 2). The mean 24 hour urinary sodium excretion in group 1 was 74 (SD 31) mmol(mEq)/24 h, and in group 2 132 (51) mmol/24 h. Compared with the screening blood pressure the average decrement of the supine blood pressure in group 1 was 16.0/8.6 mm Hg with placebo, 21.7/11.5 mm Hg with the diuretic, 28.5/17.8 mm Hg with the beta blocker, and 28.9/18.4 mm Hg with the combined agent; in group 2 these values were 13.3/6.1, 20.3/9.7, 21.3/12.9, and 29.4/16.8 mm Hg, respectively. There was a sharp decrease of the average potassium concentration during chlorthalidone and combination treatment periods (average value 3.3 mmol(mEq)/1). These results suggest that moderate salt restriction used as sole treatment has a limited though demonstrable blood pressure lowering effect but that when it is used as an adjuvant to beta blocker treatment its value is greatly enhanced.",
"In a double-blind, parallel-group multicentre study, the efficacy and safety of a fixed low-dose combination of ramipril 2.5 mg and hydrochlorothiazide (HCT) 12.5 mg was compared with each of the component drugs when given as monotherapy. After a four-week placebo run-in, patients were randomized to receive either ramipril 2.5 mg (n = 218) or HCT 12.5 mg (n = 220), or the fixed-dose combination of ramipril 2.5 mg and HCT 12.5 mg (n = 222), for a period of eight weeks. At the end of the study, in which 624 patients had completed treatment, it was found that the decrease in supine diastolic blood pressure (the main efficacy parameter) was greater in the ramipril-HCT combination group than in either the ramipril or the HCT monotherapy groups, the difference being statistically significant when compared with the HCT group (-14.3, -13.1 and -12.4 mm Hg, respectively). Reductions in standing DBP and supine and standing systolic blood pressure (SBP) were also greatest in the combination group. The incidence of adverse events was lower in the combination group than in either of the monotherapy groups, and there were no serious clinically significant laboratory abnormalities in the combination group.",
"The pharmacokinetics and pharmacodynamics of the angiotensin (AT) II receptor, AT1-subtype, antagonist candesartan were investigated in a dose-finding study in 232 patients of either gender, aged 28-69 years and weighing 54-110 kg. The study was a double-blind, placebo-controlled trial in which oral doses of 2, 4, 8, 12 and 16 mg once daily were given as the pro-drug candesartan cilexetil from day 0 to day 28.\n The population pharmacokinetics of candesartan could be best described by a two-compartment body model, parameterized in terms of clearance (14.1 1.h-1), central volume of distribution (118 1), peripheral volume (272 1) and intercompartmental clearance (15.4 1.h-1). From these model parameters, a cumulation half-life (t1/2, beta) of 29 h was derived. Age and weight were influencing factors for the distribution and elimination of the drug. Systolic and diastolic blood pressure were lowered by the treatment in a dose-dependent fashion. The maximum effect of each dose was reached after repeated administration. The link between plasma concentrations and effect could be described by a linear model when trough concentrations and blood pressure, measured at the same time, were modelled. In this model, the time dependence is implicitly handled as the trough concentrations increased during repeated administration. After treatment with the highest dose used in the trial (16 mg), the population estimate for the diastolic blood pressure was reduced from 103.2 mmHg (pre-dose day 0) to 93.3 mmHg (on day 29) and the systolic blood pressure from 154.6 mmHg (pre-dose day 0) to 137.9 mmHg (on day 29). None of the covariates (age, weight, gender) had an influence on the concentration-effect relationship.",
"The present study investigated the efficacy, safety, and utility of starting an alpha(1d)-selective antagonist, naftopidil, at 75 or 25 mg/day in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH).\n In this prospective comparative study, the subjects comprised 153 patients with LUTS associated with BPH. Patients were randomized to receive either 25 mg/day (Group LD) or 75 mg/day (Group HD) of naftopidil for 4 weeks. The lower urinary tract disease symptom score (LUTDSS), the International Prostate Symptom Score (IPSS), the Quality of life assessment index, the maximum flow rate (Q(max)), and the residual urine volume were compared between the groups.\n In both groups, the LUTDSS and the IPSS were significantly improved at the endpoint and no significant intergroup differences were identified. However, the improvement in the Q(max) was significantly better for Group HD than for Group LD. The overall efficacy did not differ significantly between the groups. The degree of improvement in voiding symptoms and LUTDSS among patients with moderate symptoms was significantly greater for Group HD than for Group LD. The frequency of adverse reactions did not differ significantly between the groups.\n Starting administration at 75 mg/day rather than 25mg/day is helpful for LUTS associated with BPH for patients with moderate symptoms, particularly in improving voiding symptoms. The 75 mg/day administration was considered to be a recommendable therapeutic dose in some patients.",
"Although several important studies have been performed in hypertensive type 2 diabetic patients, it is not known whether lowering blood pressure in normotensive (BP <140/90 mm Hg) patients offers any beneficial results on vascular complications. The current study evaluated the effect of intensive versus moderate diastolic blood pressure (DBP) control on diabetic vascular complications in 480 normotensive type 2 diabetic patients.\n The current study was a prospective, randomized controlled trial in normotensive type 2 diabetic subjects. The subjects were randomized to intensive (10 mm Hg below the baseline DBP) versus moderate (80 to 89 mm Hg) DBP control. Patients in the moderate therapy group were given placebo, while the patients randomized to intensive therapy received either nisoldipine or enalapril in a blinded manner as the initial antihypertensive medication. The primary end point evaluated was the change in creatinine clearance with the secondary endpoints consisting of change in urinary albumin excretion, progression of retinopathy and neuropathy and the incidence of cardiovascular disease.\n The mean follow-up was 5.3 years. Mean BP in the intensive group was 128 +/- 0.8/75 +/- 0.3 mm Hg versus 137 +/- 0.7/81 +/- 0.3 mm Hg in the moderate group, P < 0.0001. Although no difference was demonstrated in creatinine clearance (P = 0.43), a lower percentage of patients in the intensive group progressed from normoalbuminuria to microalbuminuria (P = 0.012) and microalbuminuria to overt albuminuria (P = 0.028). The intensive BP control group also demonstrated less progression of diabetic retinopathy (P = 0.019) and a lower incidence of strokes (P = 0.03). The results were the same whether enalapril or nisoldipine was used as the initial antihypertensive agent.\n Over a five-year follow-up period, intensive (approximately 128/75 mm Hg) BP control in normotensive type 2 diabetic patients: (1) slowed the progression to incipient and overt diabetic nephropathy; (2) decreased the progression of diabetic retinopathy; and (3) diminished the incidence of stroke.",
"The antihypertensive effectiveness of twice-daily dosing with the converting enzyme inhibitor, captopril, was examined in a multicenter study of 294 patients (181 white, 111 black, two oriental) with essential hypertension whose supine diastolic blood pressure (SDBP) was 95 mm Hg or higher after 4 to 6 weeks of preliminary placebo administration. In this double-blind study, the patients were randomized into one placebo and three captopril-treated groups: twice-daily placebo (n = 77) or twice-daily captopril 25 mg (n = 77), 50 mg (n = 71), or 100 mg (n = 69). The average decreases in SDBP after 8 weeks of treatment were 5.2%, 7.7%, 11.7%, and 10.5%, respectively. Only the two higher dose groups differed significantly from the placebo group; they also differed from the lowest dose group. The proportions of patients classified as having normalized pressures (SDBP less than 90 mm Hg) in the four groups were 39%, 47%, 70%, and 50%. If the results were analyzed by race, all three captopril-treated groups differed significantly from the placebo-treated group in the white patients but not in the black patients. However, direct comparisons between the white and black groups showed a difference only at the low, 25 mg twice daily (b.i.d.), captopril dose. Thus, although conventionally given on a three-times daily basis, the twice-daily (12-hourly) administration of captopril provides effective antihypertensive treatment in doses of 50 or 100 mg b.i.d. Moreover, white patients also exhibit a significant response to captopril at doses as low as 25 mg b.i.d.(ABSTRACT TRUNCATED AT 250 WORDS)",
"Cilazapril (CLZ) is a new, long-acting nonsulfhydril converting enzyme inhibitor (ACE-I). Its effect on peak and trough sitting diastolic blood pressure (SDBP) was studied in a total of 85 patients with uncomplicated, essential hypertension at three centers. After 4 weeks of a single-blind placebo (PLA) run-in period, patients whose SDBP was between 100 and 115 mm Hg, were randomized into active treatment with either PLA (n = 27), CLZ 2.5 mg (n = 29), or CLZ 5 mg (n = 29) once daily in a double-blind fashion for another 8 weeks. At the end of the PLA run-in and after 4 and 8 weeks active therapy, an hourly blood pressure (BP) profile during 1-10 and 21-24 h postdose was performed. The drop in SDBP at the end of the active treatment period at peak and trough was statistically and clinically significant for both CLZ doses in comparison with the PLA group. The peak/trough ratio after subtraction of the PLA effect was 62% for CLZ 2.5 mg and 59% for CLZ 5 mg. These results indicate that the dose regimen of CLZ 2.5-5 mg once daily is adequate and effective for 24 h.",
"Hypertensive emergencies, and to a certain extent their treatment, contribute to morbidity and mortality in elderly patients. We studied 22 hospitalized patients, aged 70-90 years, all of whom had moderate essential hypertensive. During acute hypertension, mean systolic and diastolic blood pressure rose to 230 +/- 24 and 120 +/- 22 mmHg, respectively. Symptoms of reduced tissue perfusion/oxygenation and/or organ failure occurred, forcing us to begin antihypertensive therapy. We administered 50 mg of the angiotensin converting enzyme (ACE) inhibitor captopril sublingually, and within 15 min, systolic blood pressure decreased by an average 60 +/- 16 mmHg and diastolic blood pressure by an average 25 +/- 14 mmHg. There was no significant change in the heart rate. In addition, we treated 22 comparable patients with 10 mg nifedipine sublingually and observed, in four cases, a greater fall in blood pressure (up to 90 mmHg) together with tachycardia. These results show the beneficial effects of captopril in the treatment of hypertensive emergencies in elderly patients. The absence of dangerous side effects indicates that ACE inhibitors can be used as first-choice drugs for the treatment of acute hypertensive crises, even in old age.",
"Whether the treatment of patients with hypertension who are 80 years of age or older is beneficial is unclear. It has been suggested that antihypertensive therapy may reduce the risk of stroke, despite possibly increasing the risk of death.\n We randomly assigned 3845 patients from Europe, China, Australasia, and Tunisia who were 80 years of age or older and had a sustained systolic blood pressure of 160 mm Hg or more to receive either the diuretic indapamide (sustained release, 1.5 mg) or matching placebo. The angiotensin-converting-enzyme inhibitor perindopril (2 or 4 mg), or matching placebo, was added if necessary to achieve the target blood pressure of 150/80 mm Hg. The primary end point was fatal or nonfatal stroke.\n The active-treatment group (1933 patients) and the placebo group (1912 patients) were well matched (mean age, 83.6 years; mean blood pressure while sitting, 173.0/90.8 mm Hg); 11.8% had a history of cardiovascular disease. Median follow-up was 1.8 years. At 2 years, the mean blood pressure while sitting was 15.0/6.1 mm Hg lower in the active-treatment group than in the placebo group. In an intention-to-treat analysis, active treatment was associated with a 30% reduction in the rate of fatal or nonfatal stroke (95% confidence interval [CI], -1 to 51; P=0.06), a 39% reduction in the rate of death from stroke (95% CI, 1 to 62; P=0.05), a 21% reduction in the rate of death from any cause (95% CI, 4 to 35; P=0.02), a 23% reduction in the rate of death from cardiovascular causes (95% CI, -1 to 40; P=0.06), and a 64% reduction in the rate of heart failure (95% CI, 42 to 78; P<0.001). Fewer serious adverse events were reported in the active-treatment group (358, vs. 448 in the placebo group; P=0.001).\n The results provide evidence that antihypertensive treatment with indapamide (sustained release), with or without perindopril, in persons 80 years of age or older is beneficial. (ClinicalTrials.gov number, NCT00122811 [ClinicalTrials.gov].).\n Copyright 2008 Massachusetts Medical Society.",
"Lisinopril (LIS) is a lysine analog of enalaprilat, the active metabolite of enalapril, an angiotensin-converting enzyme inhibitor (ACEI). Unlike enalapril, the precursor of enalaprilat, LIS is not a prodrug but has equal ACEI efficacy and potency and a slightly longer duration of action after oral administration. Short-term (12 weeks) and long-term (24 weeks) blood pressure control has been studied with LIS, hydrochlorothiazide (HCTZ), and LIS + HCTZ when given once a day. Drug treatment had three phases: (i) 2-4 weeks of single-blind placebo washout; (ii) 12 weeks of double-blind comparison therapy with LIS 20, 40, and 80 mg vs. HCTZ 12.5, 25, and 50 mg, vs. LIS + HCTZ 20 + 12.5, 40 + 25, and 80 + 50 mg; (iii) 13-24 weeks single-blind LIS vs. LIS + HCTZ. Starting double-blind therapy at the lowest dose, all three groups doubled the dose at weeks 4 and 8 if BP was not controlled with sitting diastolic BP (SDBP) less than 90 mm Hg. At the end of 12 weeks of double-blind therapy, uncontrolled HCTZ-only and LIS-only treatment groups were advanced to combination LIS + HCTZ therapy but uncontrolled LIS + HCTZ patients were dropped. Mean BP reductions (systolic/diastolic, mm Hg) for all three groups after 12 weeks of double-blind comparison therapy were: (i) LIS (n = 162), -16.6/-12.5; (ii) HCTZ (n = 155), -10.4/-6.8; (iii) LIS + HCTZ (n = 74), -23.9/-18.2 with p less than 0.01 for all groups compared to baseline.(ABSTRACT TRUNCATED AT 250 WORDS)",
"The Plaque Hypertension Lipid-Lowering Italian Study (PHYLLIS) tested whether (1) the angiotensin-converting enzyme (ACE) inhibitor fosinopril (20 mg per day) was more effective on carotid atherosclerosis progression than the diuretic hydrochlorothiazide (25 mg per day), (2) pravastatin (40 mg per day) was more effective than placebo when added to either hydrochlorothiazide or fosinopril, and (3) there were additive effects of ACE inhibitor and lipid-lowering therapies.\n A total of 508 hypertensive, hypercholesterolemic patients with asymptomatic carotid atherosclerosis were randomized to: (A) hydrochlorothiazide; (B) fosinopril; (C) hydrochlorothiazide plus pravastatin; and (D) fosinopril plus pravastatin, and followed up blindly for 2.6 years. B-Mode carotid scans were performed yearly by certified sonographers in 13 hospitals and read centrally. Corrections for drift were calculated from readings repeated at study end. Primary outcome was change in mean maximum intima-media thickness of far and near walls of common carotids and bifurcations bilaterally (CBM(max)).\n CBM(max) significantly progressed (0.010+/-0.004 mm per year; P=0.01) in group A (hydrochlorothiazide alone) but not in groups B, C, and D. CBM(max) changes in groups B, C, and D were significantly different from changes in group A. Changes in group A were concentrated at the bifurcations. \"Clinic\" and \"ambulatory\" blood pressure reductions were not significantly different between groups, but total and low-density lipoprotein cholesterol decreased by approximately 1 mmol/L in groups C and D.\n Progression of carotid atherosclerosis occurred with hydrochlorothiazide but not with fosinopril. Progression could also be avoided by associating pravastatin with hydrochlorothiazide.",
"To determine whether long-term treatment with an angiotensin-converting enzyme (ACE) inhibitor has a beneficial effect on the urinary microalbumin excretion and renal function in non-insulin-dependent diabetes mellitus (NIDDM) patients, enalapril (5 mg/day) was administered for 48 months.\n -Fifty-two patients with NIDDM who had persistent microalbuminuria in the range of 20-300 mg/24 h, serum creatinine < 106.1 microM (1.2 mg/dl), supine systolic blood pressure (BP) < 150 mmHg, supine diastolic BP < 90 mmHg, and HbA1c < 10% were divided into four groups. Twenty-six patients with normotension were divided at random into two groups; one group received enalapril (5 mg/day) (NE group), the other did not receive enalapril (NC group). In the same way, 26 other patients who were already well-controlled with nifedipine (30 mg/day) over a long-term period (4-6 years) were divided at random into two groups; one received enalapril (5 mg/day) (HE group), the other did not receive enalapril (HC group).\n After 48 months, urinary albumin excretion (UAE) was markedly reduced in group NE from 102.4 x/divided by 1.3 to 55.5 x/divided by 1.3 mg/24 h (P < 0.005), whereas no significant change occurred in group NC. In the well-controlled hypertensive groups, a significant reduction in UAE occurred in group HE (P < 0.05), whereas no significant change occurred in group HC. No changes in creatinine clearance, BP, or blood glucose control were seen during the study.\n Treatment with enalapril for 48 months may have a beneficial effect on the decline of microalbumin excretion in NIDDM patients.",
"The safety and effectiveness of different dosages and combinations of antihypertensive agents can be efficiently studied using a multifactorial trial design. In consultation with the Cardio-Renal Division of the Food and Drug Administration, we conducted a randomized, double-blind, placebo-controlled, 3 x 4 factorial trial of bisoprolol, a beta 1-selective adrenergic blocking agent, and hydrochlorothiazide.\n A total of 512 patients with mild to moderate essential hypertension were randomized to once-daily treatment with bisoprolol (0, 2.5, 10, or 40 mg), hydrochlorothiazide (0, 6.25, or 25 mg), and all possible combinations. Diastolic and systolic blood pressures were monitored during this 12-week trial.\n The effects of bisoprolol and hydrochlorothiazide were additive with respect to reductions in diastolic and systolic blood pressures over the dosage ranges studied. The addition of hydrochlorothiazide (or bisoprolol) to therapy with bisoprolol (or hydrochlorothiazide) produced an incremental reduction in blood pressure. Dosages of hydrochlorothiazide as low as 6.25 mg/d contributed a significant antihypertensive effect. A hydrochlorothiazide dosage of 6.25 mg/d produced significantly less hypokalemia and less of an increase in uric acid levels than a dosage of 25 mg/d. The low-dose combination of bisoprolol, 2.5 mg/d, and hydrochlorothiazide, 6.25 mg/d, reduced diastolic blood pressure to lower than 90 mm Hg in 61% of patients and demonstrated a safety profile that compared favorably with that of placebo.\n The utility of factorial design trials to characterize dose-response relationships and to test the potential interactions between various antihypertensive agents has been demonstrated. The combination of low dosages of bisoprolol and hydrochlorothiazide may be a rational alternative to conventional stepped-care therapy for the initial treatment of patients with mild to moderate hypertension.",
"To compare the efficacy of pentoxifylline and captopril on urinary albumin excretion (UAE) rate in non-hypertensive diabetic patients with microalbuminuria.\n 450 subjects were screened; of these 130 eligible, non-hypertensive, type 2 diabetic subjects were enrolled and randomly allocated to receive either pentoxifylline 400 mg t.i.d. (n = 65) or captopril 25 mg t.i.d. (n = 65) for six months in a randomized equivalent trial design study. Patients were eligible to participate if they had microalbuminuria, defined by UAE rate of 20-200 microg/min, and systolic/diastolic blood pressure lower than 140/85 mmHg. Diagnosis of high blood pressure and renal failure were exclusion criteria. In addition, subjects receiving ACE inhibitors or pentoxifylline were not included.\n Both treatments were well tolerated, without serious adverse events; nonetheless, one subject (1.6%) in the group with pentoxifylline had severe headache, and three (4.7%) subjects in the group with captopril had intense dry cough and nasal congestion that required stopping pentoxifylline and captopril. In addition, slight headache and mild dry cough that did not require specific treatment or interruption of medication were present in two (3.2%) and five (7.8%) subjects treated with pentoxifylline and captopril. Four subjects dropped-out (one in the pentoxifylline group and three in the captopril group). Blood pressure and fasting glucose levels were similar between the two groups throughout the study. The UAE rate decreased from the first month of treatment in the subjects of both groups, a reduction that was sustained in the following months. At the end of the study, the average UAE rate in the subjects of both groups was lower than 25 microg/min.\n Pentoxifylline showed to be an effective alternative to ACE inhibitors in reducing UAE in non-hypertensive diabetic patients with microalbuminuria.",
"National and international policy-making organizations advocate nonpharmacologic therapies to reduce blood pressure (BP). However, data to support such recommendations in older persons are virtually nonexistent. The Trials of Nonpharmacologic Intervention in the Elderly (TONE) is a randomized, controlled trial that will test whether weight loss or a reduced sodium (Na) intake or both can maintain satisfactory BP control, without unacceptable side effects, after withdrawal of antihypertensive drug therapy. Medication-treated hypertensives (aged 60 to 80 years) with a systolic BP less than 145 mm Hg and a diastolic BP less than 85 mm Hg who are taking one antihypertensive medication are randomly assigned to one of four groups: (1) weight loss alone, (2) reduced Na intake alone, (3) combined weight loss and reduced Na intake, or (4) usual life-style (control group). Overweight participants are randomized to one of these four groups, while nonoverweight individuals are assigned to either the reduced Na intake or the usual life-style group. The interventions, tailored to the needs of older persons, use behavioral approaches to accomplish intervention-specific goals (weight loss > or = 10 lb, daily Na intake < or = 80 mEqa). Three months after the start of intervention, antihypertensive drug therapy is withdrawn. The primary trial end point is a BP of 150/90 mm Hg or higher, resumption of antihypertensive drug therapy, or the occurrence of a BP-related clinical complication during 2 to 3 years of follow-up. It is anticipated that TONE findings may identify an effective and acceptable nonpharmacologic approach to control hypertension in the increasingly large number of older persons treated with antihypertensive drug therapy.",
"To compare the antihypertensive efficacy of moexipril, a new angiotensin-converting enzyme (ACE) inhibitor, to treatment with hydrochlorothiazide (HCTZ).\n Two hundred and one non-hospitalized male and female patients between 65 and 80 years of age with essential hypertension.\n This was a multicentre, placebo-controlled, double-blind study with a parallel group design. Subjects with a sitting diastolic blood pressure (DBP) > or = 95 mmHg were randomized to monotherapy with placebo, moexipiril 7.5 mg o.d., moexipril 15 mg o.d. or HCTZ 25 mg o.d. for 8 weeks.\n Throughout the study period treatment with moexipril and HCTZ resulted in significant reductions of DBP compared with placebo, but there were no significant differences between the active treatment groups. At end point the adjusted mean reductions were 10.5, 8.7 and 10.1 mmHg in the HCTZ, moexipril 7.5 mg and moexipril 15 mg groups, respectively, compared to 3.9 mmHg in the placebo group. Treatment with moexipril was associated with two cases of first dose hypotension and two cases of moderate and reversible increases in serum creatinine levels. Otherwise, both dosages of moexipril were well tolerated and the overall percentages of patients who had adverse experiences were smaller than in the placebo group.\n Moexipril is well tolerated and is at least as effective as HCTZ in elderly patients with essential hypertension.",
"This prospective, double-blind, parallel-group study randomized patients with moderate hypertension (seated systolic blood pressure (SeSBP) 160-179 mm Hg when seated diastolic blood pressure (SeDBP) <110 mm Hg; or SeDBP 100-109 mm Hg when SeSBP <180 mm Hg) 3:1:1 to treatment with irbesartan 300 mg/hydrochlorothiazide (HCTZ) 25 mg combination therapy (n=328), irbesartan 300 mg monotherapy (n=106) or HCTZ monotherapy 25 mg (n=104). Treatment was initiated at half dose, with forced titration to full dose after two weeks followed by ten further weeks' treatment. The primary efficacy variable was the mean reduction in SeSBP from baseline to week 8. Baseline characteristics were similar between groups, with mean baseline blood pressure approximately 162/98 mm Hg; the mean age was 55 years. At week 8 there was a reduction in SeSBP of 27.1 mm Hg with irbesartan/HCTZ, compared with 22.1 mm Hg with irbesartan monotherapy (P=0.0016) and 15.7 mm Hg with HCTZ (P<0.0001). Both the rate of decline and the total degree of decline achieved were greatest with irbesartan/HCTZ and least with HCTZ. A significantly greater percentage of patients reached a treatment goal of SeSBP <140 mm Hg and SeDBP <90 mm Hg by week 8 with irbesartan/HCTZ (53.4%), compared with irbesartan (40.6%; P=0.0254) and HCTZ (20.2%; P<0.0001) alone. Treatment was well tolerated in all three-treatment groups with a slight increase in adverse events in the combination therapy group. In conclusion, irbesartan/HCTZ (300/25 mg) is well tolerated and achieves rapid and sustained reductions in both systolic blood pressure and diastolic blood pressure in patients with moderate hypertension.",
"Men aged 40-64 years with mild to moderate hypertension [diastolic blood pressure (DBP) 100-130 mmHg] were randomized to treatment with a diuretic (n = 3272) or a beta-blocker (n = 3297), with additional drugs if necessary, to determine whether a beta-blocker based treatment differs from thiazide diuretic based treatment with regard to the prevention of coronary heart disease (CHD) events and death. Patients with previous CHD, stroke or other serious diseases, or with contraindications to diuretics or beta-blockers were excluded. If normotension (DBP less than 95 mmHg) was not achieved by monotherapy, other antihypertensive drugs were added, but the two basic drugs were not crossed over. Patients were assessed at 6-monthly intervals. The mean follow-up for end-points was 45.1 months. Blood pressure (BP) side effects and end-points were recorded in a standardized manner. Entry characteristics and the BP reduction achieved were very similar in both treatment groups. All analyses were made on an intention-to-treat basis. The incidence of CHD did not differ between the two treatment groups. The incidence of fatal stroke tended to be lower in the beta-blocker treated group than in the diuretic treated group. Total mortality and the total number of end-points were similar in both groups. The percentage of patients withdrawn due to side effects was similar, whereas the number of reported symptoms, according to a questionnaire, was higher for patients on beta-blockers. The incidence of diabetes did not differ between the two groups. Subgroup analyses did not detect a difference in the effect of beta-blockers compared with diuretics in smokers as opposed to non-smokers, and beta-blockers also had the same effects as diuretics in the quartile with the highest predicted risk for CHD. Beta-blockers and thiazide diuretics were approximately equally well tolerated. The two drugs had a similar BP reducing effect although additional drugs had to be given more often in the diuretic group. Antihypertensive treatment based on a beta-blocker or on a thiazide diuretic could not be shown to affect the prevention of hypertensive complications, including CHD, to a different extent.",
"Fifty-nine patients who sustained hyphema following blunt trauma were randomly assigned prospectively to either of two dose regimens of epsilon aminocaproic acid (Amicar). Twenty-six took an oral dosage of 50 mg/kg (\"half dose\") every four hours for five days, up to a maximum of 30 g/day, and 33 patients received 100 mg/kg (\"full-dose\") every four hours up to a maximum of 30 g/day. Five patients in the full-dose group experienced dizziness, hypotension, and syncope. Half-dose Amicar substantially reduced such serious side effects (P = 0.063), had no adverse effect on the reduced rate of recurrent hemorrhages (P = 0.22), and was more cost effective than the full-dose regimen. When the two patients in the half-dose group receiving 30 g/day of Amicar were deleted, however, the comparison of dizziness and hypotension in the two groups became more significant (P = 0.050). The incidence of nausea and vomiting was approximately the same in both groups (P = 0.52). Serum Amicar levels were within the range of plasminogen inhibition at both dose levels. Prior aspirin ingestion appeared to have no influence on the rate of rebleeding (P = 0.58).",
"This prospective, randomized, controlled study evaluated the impact of pharmacist-initiated home blood pressure monitoring and intervention on blood pressure control, therapy compliance, and quality of life (QOL). Subjects were 36 patients with uncontrolled stage 1 or 2 hypertension. Eighteen subjects received home blood pressure monitors, a diary, and instructions to measure blood pressure twice every morning. Home measurements were evaluated by a clinical pharmacist by telephone, and the patient's family physician was contacted with recommendations if mean monthly values were 140/90 mm Hg or higher. Eighteen control patients did not receive home monitors or pharmacist intervention. Office blood pressure measurements and QOL surveys (SF-36) were obtained at baseline and after 6 months. Mean absolute reductions in systolic and diastolic pressures were significantly reduced from baseline in intervention subjects (17.0 and 10.5 mm Hg, both p < 0.0001) but not in controls (7.0 and 3.8 mm Hg, p = 0.12 and p = 0.09). More intervention subjects (8) had blood pressure values below 140/90 at 6 months compared with controls (4). During the study 83.3% (15) of intervention subjects had drug therapy changes versus 33% (6) of controls (p < 0.01). Compliance and QOL were not significantly affected. Our data suggest that the combination of pharmacist intervention with home monitoring can improve blood pressure control in patients with uncontrolled hypertension. This may be related to increased modifications of drug regimens.",
"The extent of morning blood pressure (BP) surge upon wakening has been associated with increased incidence of stroke and cardiovascular mortality. This trial investigated the antihypertensive efficacy and effects on the morning BP surge of awakening versus bedtime administration of nifedipine in essential hypertension.\n We studied 238 previously untreated hypertensive patients (108 men and 130 women), 53.3+/-11.4 years of age, randomly assigned to receive nifedipine (30 mg/day) as a monotherapy either upon awakening or at bedtime. BP was measured for 48 h before and after 8 weeks of treatment.\n The BP reduction after the treatment was significantly greater with bedtime dosing (P<0.001). The proportion of patients with controlled ambulatory BP thus increased from 28 to 43% (P = 0.019) with bedtime treatment. The sleep time relative BP decline was unchanged after morning treatment, but increased toward a more dipping pattern after bedtime dosing (P = 0.026 between groups). The morning BP surge was unchanged after the administration of nifedipine upon awakening (1.4/1.2 mmHg reduction in systolic/diastolic BP surge, P>0.270), but significantly reduced after bedtime dosing (6.2/4.4 mmHg reduction, P<0.001).\n Nifedipine efficiently reduces BP for the entire 24 h and to a significantly larger extent after bedtime administration. The significant added efficacy on reducing night-time BP, the decrease in the prevalence of a nondipper BP pattern, and the significant decrease in morning BP surge (all relevant markers of cardiovascular morbidity and mortality) of bedtime as compared with morning administration, consistently indicate that nifedipine should preferably be administered at bedtime in patients with essential hypertension.",
"In this double-blind, randomized, parallel-group study, the aim was to compare the efficacy and tolerability of a new fixed combination of felodipine and metoprolol with the individual components in monotherapy. After a placebo period of 4 weeks, 159 patients with mild to moderate essential hypertension were randomized to extended-release formulations of either felodipine plus metoprolol 10 + 100 mg (FM), felodipine 10 mg (F), or metoprolol 100 mg (M) once daily if supine diastolic blood pressure greater than 95 mm Hg. After 12 weeks of active treatment, the reductions in supine blood pressure (24 h after dosing) were 20/14, 13/10, and 11/8 mm Hg for FM, F, and M, respectively. The difference in change was 7/4 mm Hg (p = 0.004/p = 0.006) and 8/5 mm Hg (p = 0.0002/p less than 0.0001) for the fixed combination and F or M, respectively. Blood pressure control (diastolic blood pressure less than 90 mm Hg after 12 weeks) was significantly better for the combination than for F and M, i.e., 71%, 49% (p = 0.008), and 34% (p = 0.004), respectively. Adverse experiences were those to be expected from previous studies with felodipine and metoprolol and did not differ in frequency between groups. It can be concluded that a fixed combination of metoprolol and felodipine has a clinically relevant and significantly better blood pressure reduction 24 h postdose than the individual substances in monotherapy, without decreased tolerability.",
"Persistent activation of the renin-angiotensin-aldosterone-system (RAAS) is known to occur in patients with chronic heart failure (CHF) despite treatment with angiotensin-converting enzyme inhibitor (ACE) therapy. When added to ACE inhibitors, angiotensin II type 1 (AT1) antagonists may allow more complete blockade of the RAAS and preserve the beneficial effects of bradykinin accumulation not seen with AT1 receptor blockade alone.\n Thirty-six patients with stable New York Heart Association class II-IV CHF receiving ACE inhibitor therapy were randomly assigned in a double-blind manner to receive either eprosartan, a specific competitive AT1 receptor antagonist (400 to 800 mg daily, n = 18) or placebo (n = 18) for 8 weeks. The primary outcome measure was left ventricular ejection fraction (LVEF) as measured by radionuclide ventriculography, and secondary measures were central hemodynamics assessed by Swan-Ganz catheterization and neurohormonal effects.\n There was no change in LVEF with eprosartan therapy (mean relative LVEF percentage change [SEM] +10.5% [9.3] vs +10.1% [5.0], respectively; difference, 0.4; 95% confidence interval [CI], -20.8 to 21.7; P =.97). Eprosartan was associated with a significant reduction in diastolic blood pressure and a trend toward a reduction in systolic blood pressure compared with placebo (-7.3 mm Hg [95% CI, -14.2 to -0.4] diastolic; -8.9 mm Hg [95% CI, -18.6 to 0.8] systolic). No significant change in heart rate or central hemodynamics occurred during treatment with eprosartan compared with placebo. A trend toward an increase in plasma renin activity was noted with eprosartan therapy. Eprosartan was well tolerated, with an adverse event profile similar to placebo, whereas kidney function remained unchanged.\n When added to an ACE inhibitor, eprosartan reduced arterial pressure without increasing heart rate. There was no change in LVEF after 2 months of therapy with eprosartan.",
"One third of patients treated for hypertension attain adequate blood pressure (BP) control, and multidrug regimens are often required. Given the lifelong nature of hypertension, there is a need to evaluate the long-term efficacy and tolerability of higher doses of combination anti-hypertensive therapies.\n This study investigated the efficacy and tolerability of valsartan (VAL) or hydrochlorothiazide (HCTZ)-monotherapy and higher-dose combinations in patients with essential hypertension.\n The first part of this study was an 8-week, multicenter, randomized, double-blind, placebo controlled, parallel-group trial. Patients with essential hypertension (mean sitting diastolic BP [MSDBP], > or =95 mm Hg and <110 mm Hg) were randomized to 1 of 8 treatment groups: VAL 160 or 320 mg; HCTZ 12.5 or 25 mg; VAL/HCTZ 160/12.5, 320/12.5, or 320/25 mg; or placebo. Mean changes in MSDBP and mean sitting systolic BP (MSSBP) were analyzed at the 8-week core study end point. VAL/HCTZ 320/12.5 and 320/25 mg were further investigated in a 54-week, open-label extension. Response was defined as MSDBP <90 mm Hg or a > or =10 mm Hg decrease compared to baseline. Control was defined as MSDBP <90 mm Hg compared with baseline. Tolerability was assessed by monitoring adverse events at randomization and all subsequent study visits and regular evaluation of hematology and blood chemistry.\n A total of 1346 patients were randomized into the 8-week core study (734 men, 612 women; 924 white, 291 black, 23 Asian, 108 other; mean age, 52.7 years; mean weight, 92.6 kg). All active treatments were associated with significantly reduced MSSBP and MSDBP during the core 8-week study, with each monotherapy significantly contributing to the overall effect of combination therapy (VAL and HCTZ, P < 0.001). Each combination was associated with significantly greater reductions in MSSBP and MSDBP compared with the monotherapies and placebo (all, P < 0.001). The mean reduction in MSSBP/MSDBP with VAL/HCTZ 320/25 mg was 24.7/16.6 mm Hg, compared with 5.9/7.0 mm Hg with placebo. The reduction in MSSBP was significantly greater with VAL/HCTZ 320/25 mg compared with VAL/HCTZ 160/12.5 mg (P < 0.002). Rates of response and BP control were significantly higher in the groups that received combination treatment compared with those that received monotherapy. The incidence of hypokalemia was lower with VAL/HCTZ combinations (1.8%-6.1%) than with HCTZ monotherapies (7.1%-13.3%). The majority of adverse events in the core study were of mild to moderate severity. The efficacy and tolerability of VAL/HCTZ combinations were maintained during the extension (797 patients).\n In this study population, combination therapies with VAL/HCTZ were associated with significantly greater BP reductions compared with either monotherapy, were well tolerated, and were associated with less hypokalemia than HCTZ alone.",
"Isolated systolic hypertension occurs in about 15% of people aged 60 years or older. In 1989, the European Working Party on High Blood Pressure in the Elderly investigated whether active treatment could reduce cardiovascular complications of isolated systolic hypertension. Fatal and non-fatal stroke combined was the primary endpoint.\n All patients (> 60 years) were initially started on masked placebo. At three run-in visits 1 month apart, their average sitting systolic blood pressure was 160-219 mm Hg with a diastolic blood pressure lower than 95 mm Hg. After stratification for centre, sex, and previous cardiovascular complications, 4695 patients were randomly assigned to nitrendipine 10-40 mg daily, with the possible addition of enalapril 5-20 mg daily and hydrochlorothiazide 12.5-25.0 mg daily, or matching placebos. Patients withdrawing from double-blind treatment were still followed up. We compared occurrence of major endpoints by intention to treat.\n At a median of 2 years' follow-up, sitting systolic and diastolic blood pressures had fallen by 13 mm Hg and 2 mm Hg in the placebo group (n = 2297) and by 23 mm Hg and 7 mm Hg in the active treatment group (n = 2398). The between-group differences were systolic 10.1 mm Hg (95% CI 8.8-11.4) and diastolic, 4.5 mm Hg (3.9-5.1). Active treatment reduced the total rate of stroke from 13.7 to 7.9 endpoints per 1000 patient-years (42% reduction; p = 0.003). Non-fatal stroke decreased by 44% (p = 0.007). In the active treatment group, all fatal and non-fatal cardiac endpoints, including sudden death, declined by 26% (p = 0.03). Non-fatal cardiac endpoints decreased by 33% (p = 0.03) and all fatal and non-fatal cardiovascular endpoints by 31% (p < 0.001). Cardiovascular mortality was slightly lower on active treatment (-27%, p = 0.07), but all-cause mortality was not influenced (-14%; p = 0.22).\n Among elderly patients with isolated systolic hypertension, antihypertensive drug treatment starting with nitrendipine reduces the rate of cardiovascular complications. Treatment of 1000 patients for 5 years with this type of regimen may prevent 29 strokes or 53 major cardiovascular endpoints.",
"The purpose of the present study was to examine the effects of salt-restriction alone and in combination with an angiotensin-converting enzyme (ACE) inhibitor (cilazapril) on both office and ambulatory blood pressure (BP) levels in free living subjects with elevated BP. The study was carried out in an out-patient setting with subjects recruited from occupational health care system mainly. After exclusions, 39 subjects (24 men, 15 women, aged 28-65 years) with mildly to moderately elevated BP completed the study. After 3 months run-in period with placebo (first month on normal-salt and the next 2 months on sodium-restricted diet) the subjects were randomised into either salt-restriction placebo or salt-restriction cilazapril (2.5 mg daily) groups for 3 months. In the whole group, 24-h urinary sodium excretion decreased (mean +/- s.d.) from 198 +/- 60 to 112 +/- 59 mmol (4 weeks vs 24 weeks, P < 0.001). Systolic and diastolic office BP decreased during the placebo-sodium-restriction phase (-7.1 [95% Cl -11.2; -3.0] and -4.2 [95% Cl -6.6; -1.8] mm Hg for systolic and diastolic BP), and similarly the daytime ambulatory BP (ABP) was reduced during this period (-2.8 [95% Cl -5.2; -0.5] and -2.8 [95% Cl -4.5; -1.2] mm Hg, systolic (SBP) and diastolic blood pressure (DBP) respectively). No changes were observed in the night time ABP. Addition of cilazapril to sodium-restriction enhanced significantly the office BP (-13.2, [95% Cl -20.2; -6.2], and -9.1 [95% Cl -13.5; -4.7]) and daytime ABP (-5.9, [95% Cl -10.1; -1.8] and -5.3, [95% Cl -8.8; -1.9]) reduction. Blood glucose, plasma insulin or serum lipids did not change during the study. Moderate sodium restriction seems to lower the office and daytime ABP levels in subjects with mild-to-moderate hypertension. The antihypertensive effect of cilazapril could be enhanced by sodium restriction.",
"This multicenter, placebo-controlled, double-blind trial of factorial design evaluated the safety and efficacy of combination treatment with the angiotensin-converting enzyme inhibitor, enalapril, and the vascular selective calcium antagonist felodipine extended release (ER) in patients with essential hypertension. After a 4-week, single-blind placebo baseline period, 707 patients with sitting diastolic blood pressures (BPs) in the range of 95 to 115 mm Hg received placebo, enalapril (5 or 20 mg), felodipine ER (2.5, 5, or 10 mg), or their combinations for an 8-week double-blind treatment period. All doses of enalapril and felodipine ER had a statistically significant (p < 0.05) additive effect in reducing both systolic and diastolic BP. The trough to peak ratios for the combinations ranged from 0.63 (enalapril 5 mg-felodipine ER 2.5 mg) to 0.79 (enalapril 20 mg-felodipine ER 10 mg) and were consistent with effective BP control with 1 dose/day. Patients aged > or = 65 years demonstrated a greater reduction in diastolic BP. Combinations of enalapril-felodipine ER were associated with less drug-induced peripheral edema (4.1%) compared to felodipine ER monotherapy (10.8%). There were no serious drug-related adverse effects observed during the study. In this trial, the combination of enalapril and felodipine ER effectively lowered BP and was generally well tolerated with an excellent safety profile when used in the treatment of hypertension.",
"The Intravenous Nimodipine West European Stroke Trial (INWEST) found a correlation between nimodipine-induced reduction in blood pressure (BP) and an unfavorable outcome in acute stroke. We sought to confirm this correlation with and without adjustment for prognostic variables and to investigate outcome in subgroups with increasing levels of BP reduction.\n Patients with a clinical diagnosis of ischemic stroke (within 24 hours) were consecutively allocated to receive placebo (n=100), 1 mg/h (low-dose) nimodipine (n=101), or 2 mg/h (high-dose) nimodipine (n=94). The correlation between average BP change during the first 2 days and the outcome at day 21 was analyzed.\n Two hundred sixty-five patients were included in this analysis (n=92, 93, and 80 for placebo, low dose, and high dose, respectively). Nimodipine treatment resulted in a statistically significant reduction in systolic BP (SBP) and diastolic BP (DBP) from baseline compared with placebo during the first few days. In multivariate analysis, a significant correlation between DBP reduction and worsening of the neurological score was found for the high-dose group (beta=0.49, P=0. 048). Patients with a DBP reduction of > or =20% in the high-dose group had a significantly increased adjusted OR for the compound outcome variable death or dependency (Barthel Index <60) (n/N=25/26, OR 10. 16, 95% CI 1.02 to 101.74) and death alone (n/N=9/26, OR 4.336, 95% CI 1.131 16.619) compared with all placebo patients (n/N=62/92 and 14/92, respectively). There was no correlation between SBP change and outcome.\n DBP, but not SBP, reduction was associated with neurological worsening after the intravenous administration of high-dose nimodipine after acute stroke. For low-dose nimodipine, the results were not conclusive. These results do not confirm or exclude a neuroprotective property of nimodipine.",
"Stratum 2 of the Ramipril Efficacy in Nephropathy (REIN) study has already shown that in patients with chronic nephropathies and proteinuria of 3 g or more per 24 h, angiotensin-converting enzyme (ACE) inhibition reduced the rate of decline in glomerular filtration and halved the combined risk of doubling of serum creatinine or end-stage renal failure (ESRF) found in controls on placebo plus conventional antihypertensives. In REIN stratum 1, reported here, 24 h proteinuria was 1 g or more but less than 3 g per 24 h.\n In stratum 1 of this double-blind trial 186 patients were randomised to a ramipril or a control (placebo plus conventional antihypertensive therapy) group targeted at achieving a diastolic blood pressure of less than 90 mm Hg. The primary endpoints were change in glomerular filtration rate (GFR) and time to ESRF or overt proteinuria (> or =53 g/24 h). Median follow-up was 31 months.\n The decline in GFR per month was not significantly different (ramipril 0.26 [SE 0.05] mL per min per 1.73m2, control 0.29 [0.06]). Progression to ESRF was significantly less common in the ramipril group (9/99 vs 18/87) for a relative risk (RR) of 2.72 (95% CI 1.22-6.08); so was progression to overt proteinuria (15/99 vs 27/87, RR 2.40 [1.27-4.52]). Patients with a baseline GFR of 45 mL/min/1.73 m2 or less and proteinuria of 1.5 g/24 h or more had more rapid progression and gained the most from ramipril treatment. Proteinuria decreased by 13% in the ramipril group and increased by 15% in the controls. Cardiovascular events were similar. As expected, the rate of decline in GFR and the frequency of ESRF were much lower in stratum 1 than they had been in stratum 2.\n In non-diabetic nephropathies, ACE inhibition confers renoprotection even to patients with non-nephrotic proteinuria.",
"The purpose of this study was to assess whether long-term (8 years) inhibition of angiotensin-converting enzyme (ACE) protects kidney function in normotensive type 1 diabetic patients with diabetic nephropathy.\n We performed an open randomized follow-up study of normotensive type 1 diabetics with nephropathy either treated (N = 15) or not (N = 17) with captopril twice per day (average 74, range 12.5 to 125 mg/day). The main outcome measures were arterial blood pressure, albuminuria, and glomerular filtration rate (GFR; 51Cr-EDTA plasma clearance, twice yearly).\n Arterial blood pressure (mm Hg) was kept constant in the captopril group, at baseline (mean, SEM), 128/78 (3/2) and during follow-up 129/77 (4/1) but increased significantly in the control group from 127/79 (2/1) to 137/84 (5/2) (P < 0.01). Furthermore, 8 out of the 17 control subjects required treatment with blood pressure-lowering drugs because they developed hypertension. The fractional albumin clearance (x10-5) remained unchanged in the captopril group: baseline [10.8 (1.25) geometric mean and antilog (SEM)] during the eight years [11.8 (1.47)], while a significant rise occurred in control patients: 13.3 (1.23) to 26.2 (1.42) (P < 0.05). Baseline GFR was nearly identical: 111 (6) and 115 (4) mL/min/1.73 m2 in the captopril and control group, respectively. The median (range) rate of decline in GFR (mL/min/year) was 1.7 (10.7 to -2.0) in the captopril group versus 2.8 (17.7 to -2.6) in the control group (P = NS).\n The beneficial effect of captopril in arresting the rise in systemic blood pressure and albuminuria is long lasting. A loss in GFR is minimal in most patients with diabetic nephropathy if normotension is sustained by prospective treatment with ACE inhibitors or restored by implementation of other antihypertensive medications with the development of hypertension.",
"Repeated blood pressure recordings by non-invasive devices are of better predictive value than single measurements in the evaluation of antihypertensive treatment. Such a method has been used to establish the dose-effect relationship of perindopril. After a two-week placebo run-in period, 40 patients with essential hypertension (age 56.6 +/- 1.5 years, 31 males, nine females) were treated with placebo or 2, 4 or 8 mg of perindopril once daily for one month following a randomized double-blind design. They were included if at least 75% of diastolic blood pressure recordings, made over an 8 h diurnal period using an automatic blood pressure recorder, were greater than 95 mmHg on placebo. Values (mean +/- SEM) before and after treatment were assessed using analysis of variance. These data showed a significantly greater reduction of blood pressure with 4 mg and 8 mg daily doses compared to placebo and the 2 mg daily dose. Such results were not obtained with blood pressure levels recorded by a mercury sphygmomanometer, confirming the value of an automatic blood pressure recorder as a tool in therapeutic trials.",
"Despite the beneficial effects of blockade of the renin-angiotensin system in diabetic nephropathy (DN), albuminuria and progression of renal disease are not completely halted by these agents. Therefore, it is necessary to explore potential antiproteinuric and renoprotective effects of innovative therapeutic approaches. This study tested the hypothesis that the combination of pentoxifylline (PTF) with angiotensin II receptor blockers in normotensive patients with type 2 diabetes produces an additive antiproteinuric effect. Sixty-one patients with DN and residual albuminuria despite treatment with the recommended doses of ARB for >1 yr were randomly assigned to receive the addition of 1200 mg of PTF daily (n = 30) or to a control group (n = 31). Baseline characteristics were similar between groups, and correlation analysis showed a significant association between urinary albumin excretion (UAE) and urinary TNF-alpha (R = 0.53, P < 0.001). After 4 mo, albuminuria showed a significant decrease in patients who received PTF, from 900 mg/24 h (466 to 1542 mg/d) to 791 mg/24 h (309 to 1400 mg/d; P < 0.001), whereas no significant changes were observed in the control group: 920 mg/24 h (450 to 1489 mg/d) at baseline, and 900 mg/24 h (428 to 1800 mg/d) at the end of the study. The mean percentage variation of UAE in the treatment and control groups was -16.7 and 5.5%, respectively (between-group comparison, P < 0.001). This additive antiproteinuric effect was not dependent on changes in BP or metabolic control. However, both serum and urinary levels of TNF-alpha also decreased in patients who received PTF, from 6.4 pg/ml (2.1 to 9.7) and 16 pg/mg (8 to 29) at baseline to 4.6 pg/ml (0.4 to 9) and 14.2 pg/mg (3 to 26) at the end of the study, respectively (P < 0.01), without significant variations in control patients. Moreover, regression analysis at the end of the study showed a correlation between the change in UAE and the change in urinary TNF-alpha in patients who were treated with PTF (R = 0.49, P < 0.001). In conclusion, administration of PTF to patients who have type 2 diabetes and are under long-term treatment with an ARB produces a significant additive antiproteinuric effect associated with a reduction of urinary TNF-alpha excretion.",
"To compare the efficacy of aprotinin (APR) and tranexamic acid (TRA) in reducing blood loss and transfusion requirements after cardiac surgery under extracorporeal circulation (ECC).\n Randomized controlled trial.\n One hundred and four adults undergoing either coronary artery bypass grafting (CABG) (n = 55), or aortic valve replacement (AVR) (n = 49), allocated into three groups.\n a) APR group (23 CABG and 20 AVR) received aprotinin, 2 x 10(6) KIU (280 mg) after induction, followed by an infusion of 0.5 x 106 KIU.h-1 (70 mg.h-1) until chest closure, with a supplement to the oxygenator prime of 2 x 10(6) KIU; b) TRA group (22 CABG and 19 AVR) received tranexamic acid, 15 mg.kg-1 between the injection of heparin (400 IU.kg-1) and the beginning of ECC, 15 mg.kg-1 after protamin injection (1.3 mg/100 IU of heparin); c) CTR group (10 CABG and 10 AVR), the control group, was not treated with an antifibrinolytic agent. The amount of blood collected from the chest tube drainage was measured at admission to ICU, as well as 4, 8 and 18 h after the insertion of drains and at the time of their removal. Packed red cells where given when the haematocrit was under 20% during ECC, 25% at the end of surgery and 30% after extubation.\n The blood loss was lower in APR group (834 +/- 448 mL) than in TRA group (1015 +/- 409 mL) (P = 0.009), and in CTR group (1416 +/- 559 ML) (P = 0.004). The rates of transfused patients in groups APR, ATR and CTR were 35, 37 and 60% respectively and the numbers of units administered per patient were 0.8, 0.8 and 1.7 respectively. In AVR cases, APR and TRA had a similar efficacy. In CABG cases, only aprotinin decreased postoperative bleeding. However there was no difference between APR and TRA concerning the transfusion requirements. In CABG cases the ECC was of shorter duration and blood loss was 1127 +/- 540 mL vs 894 +/- 422 mL in AVR cases (P = 0.03).\n Both APR and TRA decrease blood loss. APR is more efficient after CABG than TRA as far as blood loss is concerned, whereas the transfusion requirements are similar. As APR is about 100 times more expensive and carries a risk for allergic reactions, its use in a high dose regimen is only recommended for reoperations, in patients treated with salicylates and in case of sepsis.",
"We investigated in a double-blind study whether metformin reduces blood pressure (BP) in patients with Type 2 diabetes intensively treated with insulin.\n A total of 220 patients with Type 2 diabetes were asked to undergo 24-h ambulatory BP monitoring (24-h ABPM). One hundred and eighty-two gave informed consent. Eighty-nine were randomized to metformin and 93 to placebo. Thirty-five subjects dropped out (13 placebo, 22 metformin users); 147 patients underwent a second 24-h ABPM, 16 weeks after randomization.\n Systolic BP (SBP), diastolic BP (DBP), pulse BP (PP), mean BP (MP) and heart rate (HR) were measured as office BP measurements and as 24-h ABPM for 24-h, day and night. Office BP measurements did not differ significantly between the placebo- and metformin-treated groups for any BP measure, but showed a non-significant trend for SBP reduction with metformin use (mean baseline-adjusted difference, metformin minus placebo: -4.2 mmHg, 95% CI, -9.9 to +1.5; P = 0.15). The baseline-adjusted differences of the ambulatory measurements were -0.2 mmHg (95% CI, -2.9 to +2.6) for the 24-h SBP, and +1.1 mmHg (95% CI, -0.7 to +2.8) for the 24-h DBP. On the whole, BP differences between metformin- and placebo-treated groups were not statistically significant. The only significant difference was for night-time PP (baseline-adjusted difference: -2.2 mmHg; 95% CI, -4.2 to -0.2). These results were not different after adjustment for age and diabetes duration, or for (changes in) body mass index, glycated haemoglobin, insulin dose or plasma homocysteine.\n Metformin does not significantly affect BP in patients with Type 2 diabetes intensively treated with insulin.",
"Second-generation and third-generation oral contraceptives containing 30 mcg or more of ethinylestradiol (EE) decrease insulin sensitivity (SI). In this study, we investigated whether SI is decreased by contraceptives containing lower doses EE or by progestins with antiandrogenic properties.\n Twenty-eight young healthy women were randomly allocated to receive 20 mcg of EE and 150 mcg of desogestrel (DSG) (n=14) or 30 mcg of EE and 2 mg of chlormadinone acetate (CMA) (n=14) for 6 months. SI and glucose utilization independent of insulin (Sg) were investigated by the minimal model method. Lipid modifications were also analyzed.\n SI decreased with EE/DSG (7.09+/-1.4 vs. 4.30+/-0.91; p=.04; n=12), but not with EE/CMA (5.79+/-0.93 vs. 6.79+/-1.1; p=.48; n=12). SI modifications observed in the two groups were significantly different (-2.79+/-1.15 vs. 1.0+/-1.38; p=.05). Sg did not vary with either treatment. The response of C-peptide to glucose increased, but significantly so only with EE/CMA (p=.01). The C-peptide/insulin response increased with both EE/DSG (p=.05) and EE/CMA (p=.04). High-density lipoprotein (HDL) cholesterol (p=.02) and triglycerides (p=.02 and p=.01) increased in both groups, but HDL/low-density lipoprotein cholesterol (p=.02), apoprotein A1 (Apo-A1) (p=.04) and Apo-A1/apoprotein B (p=.048) increased significantly only with EE/CMA.\n The present study confirms that DSG, even when associated with low EE dose, decreases SI. By contrast, EE/CMA does not deteriorate SI and induces a favorable lipid profile.",
"To evaluate the efficacy and tolerability of nitrendipine in comparison with captopril in hypertensive diabetic patients with left ventricular hypertrophy (LVH).\n A total of 75 patients enrolled in this study presented stable type 2 diabetes (not treated with insulin) and mild-to-moderate hypertension with a left ventricular mass > or = 75 g/m2 by two-dimensional echocardiography. After a 4-week washout period, 38 patients were assigned to treatment with captopril, and 37 patients to nitrendipine (random allocation). The duration of follow-up was 36 weeks.\n Patients of both groups were similar with regard to the duration of diabetes and hypertension, systolic and diastolic blood pressure at rest, degree of LVH, metabolic control, and albumin excretion rate (AER). Both drugs were equally effective in reducing systolic and diastolic blood pressure (captopril: from 165 +/- 13/100 +/- 4 to 147 +/- 11/87 +/- 4 mmHg; nitrendipine: from 167 +/- 17/100 +/- 5 to 143 +/- 9/86 +/- 4 mmHg; P < 0.05) and in reversing LVH (nitrendipine: from 87 +/- 2 to 81 +/- 1 g/m2; captopril: from 89 +/- 2 to 85 +/- 2 g/m2; P = 0.0001). Neither the left ventricular end-diastolic volume index nor the left ventricular ejection fraction changed significantly during the treatment period.\n Nitrendipine is as effective as captopril in reducing both systolic and diastolic blood pressure and in reversing LVH. Neither drug showed any negative side effects on fasting plasma glucose and glycated hemoglobin (HbA1c) levels, and both maintain constant AERs.",
"Most hypertensive renal transplant recipients require two or more antihypertensive medications to achieve blood pressure control. However, which medications must be combined is still a matter of debate.\n A prospective randomized open-label blinded evaluation trial comparing the six-month effects of the amlodipine-enalapril combination (n = 32) vs. enalapril alone (n = 33) and vs. amlodipine alone (n = 34) on arterial pressure, renal function, albuminuria and tolerability.\n At six months, diastolic arterial pressure was more adequately controlled (i.e., <90 mmHg) in the combination group than in the amlodipine and enalapril groups (100% vs. 82.4% and 84.8%, respectively, p = 0.038). The same trend was observed for systolic arterial pressure (65.6% vs. 58.8% and 51.5%, NS). The six-month change in albuminuria was similar in the combination group and in the enalapril group (-64.7% vs. -59.5%); however, patients in the combination group exhibited a greater reduction in albuminuria than in the amlodipine group (-64.7% vs. -29.0%, p = 0.002). As compared with baseline values, serum creatinine and potassium remained unchanged in the combination group, whereas they increased by 9 +/- 12 micromol/L (p = 0.01) and by 0.2 +/- 0.4 mmol/L (p < 0.01), respectively, in the enalapril group. The cyclosporine trough levels remained unchanged in the combination group, but increased in the amlodipine group.\n Angiotensin-converting enzyme inhibitor (ACEI)-calcium-channel blocker (CCB) combination controls arterial pressure more adequately than ACEI alone or CCB alone, reduces albuminuria and may prevent the ACEI-induced initial rise in serum creatinine."
] |
There are no clinically meaningful BP lowering differences between different ACE inhibitors. The BP lowering effect of ACE inhibitors is modest; the magnitude of trough BP lowering at one-half the manufacturers' maximum recommended dose and above is -8/-5 mm Hg. Furthermore, 60 to 70% of this trough BP lowering effect occurs with recommended starting doses. The review did not provide a good estimate of the incidence of harms associated with ACE inhibitors because of the short duration of the trials and the lack of reporting of adverse effects in many of the trials.
|
CD004452
|
[
"10819855",
"2197860",
"10972368"
] |
[
"An oxytocin receptor antagonist (atosiban) in the treatment of preterm labor: a randomized, double-blind, placebo-controlled trial with tocolytic rescue.",
"A comparison of tocolysis with nifedipine or ritodrine: analysis of efficacy and maternal, fetal, and neonatal outcome.",
"Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT)."
] |
[
"This study was designed to evaluate the efficacy and safety of the oxytocin receptor antagonist atosiban in the treatment of preterm labor.\n A multicenter, double-blind, placebo-controlled trial with tocolytic rescue was designed. Five hundred thirty-one patients were randomized to receive, and 501 received, either intravenous atosiban (n = 246) or placebo (n = 255), followed by subcutaneous maintenance with the assigned agent. Standard tocolytics as rescue tocolysis were permitted after 1 hour of either placebo or atosiban if preterm labor continued. The primary end point was the time from the start of study drug to delivery or therapeutic failure. Secondary end points were the proportion of patients who remained undelivered and did not receive an alternate tocolytic at 24 hours, 48 hours, and 7 days.\n No significant difference was found in the time from start of treatment to delivery or therapeutic failure between atosiban and placebo (median, 25.6 days vs 21.0 days, respectively; P =.6). The percentages of patients remaining undelivered and not requiring an alternate tocolytic at 24 hours, 48 hours, and 7 days were significantly higher in the atosiban group than in the control group (all P < or =.008). A significant treatment-by-gestational age interaction existed for the 48-hour and 7-day end points. Atosiban was consistently superior to placebo at a gestational age of > or =28 weeks. Fourteen atosiban-treated patients and 5 placebo-treated patients were randomized at <24 weeks; the incidence of fetal-infant deaths was higher for the atosiban group at <24 weeks. Maternal-fetal adverse events were similar except for injection-site reactions, which occurred more often with atosiban.\n In this trial the treatment of patients in preterm labor with atosiban resulted in prolongation of pregnancy for up to 7 days for those at a gestational age > or =28 weeks, and this occurred with a low rate of maternal-fetal adverse effects. In addition, at a gestational age > or =28 weeks, the infant morbidity and mortality of atosiban-initiated standard care were similar to those with placebo-initiated standard care. Given that all patients in this study were eligible for tocolysis and that, in practice, nearly all patients who are eligible for a tocolytic receive one, the benefit of using atosiban is the placebo-like maternal-fetal side effect profile. These observations support the use of this oxytocin receptor antagonist in the treatment of patients in preterm labor with intact membranes. Efficacy and infant outcome data at <28 weeks are inconclusive.",
"Nifedipine, a dihydropyridone calcium entry blocker, has been used with increasing frequency in the treatment of preterm labor. We studied 66 patients in this prospective, randomized trial to evaluate the efficacy and maternal, fetal, and neonatal outcome associated with tocolysis with nifedipine or ritodrine. Delivery was delayed for 48 hours, 7 days, and until the thirty-sixth week of gestation in 84%, 70%, and 41%, respectively, of patients in the nifedipine group, compared with 72%, 63%, and 52% of patients in the ritodrine group (difference not significant). Maternal side effects were more common and more serious in the group of patients who received ritodrine compared with those who received nifedipine (18 of 38 versus 5 of 38, p less than 0.01); however, fetal and neonatal outcome appeared to be similar when the groups were compared. On the basis of this study, it appears that tocolysis with either nifedipine or ritodrine is equally efficacious; however, maternal side effects are less common with nifedipine treatment. We conclude that nifedipine may have a role in the treatment of preterm labor but suggest further careful evaluation of this agent before it is considered for routine clinical use.",
"The efficacy of antihypertensive drugs newer than diuretics and beta-blockers has not been established. We compared the effects of the calcium-channel blocker nifedipine once daily with the diuretic combination co-amilozide on cardiovascular mortality and morbidity in high-risk patients with hypertension.\n We did a prospective, randomised, double-blind trial in Europe and Israel in 6321 patients aged 55-80 years with hypertension (blood pressure > or = 150/95 mm Hg, or > or = 160 mm Hg systolic). Patients had at least one additional cardiovascular risk factor. We randomly assigned patients nifedipine 30 mg in a long-acting gastrointestinal-transport-system (GITS) formulation (n=3157), or co-amilozide (hydrochlorothiazide 25 mg [corrected] plus amiloride 2.5 mg; n=3164). Dose titration was by dose doubling, and addition of atenolol 25-50 mg or enalapril 5-10 mg. The primary outcome was cardiovascular death, myocardial infarction, heart failure, or stroke. Analysis was done by intention to treat.\n Primary outcomes occurred in 200 (6.3%) patients in the nifedipine group and in 182 (5.8%) in the co-amilozide group (18.2 vs 16.5 events per 1000 patient-years; relative risk 1.10 [95% CI 0.91-1.34], p=0.35). Overall mean blood pressure fell from 173/99 mm Hg (SD 14/8) to 138/82 mm Hg (12/7). There was an 8% excess of withdrawals from the nifedipine group because of peripheral oedema (725 vs 518, p<0.0001), but serious adverse events were more frequent in the co-amilozide group (880 vs 796, p=0.02). Deaths were mainly non-vascular (nifedipine 176 vs co-amilozide 172; p=0.81). 80% of the primary events occurred in patients receiving randomised treatment (157 nifedipine, 147 co-amilozide, difference 0.33% [-0.7 to 1.4]).\n Nifedipine once daily and co-amilozide were equally effective in preventing overall cardiovascular or cerebrovascular complications. The choice of drug can be decided by tolerability and blood-pressure response rather than long-term safety or efficacy."
] |
This review failed to demonstrate the superiority of atosiban over betamimetics or placebo in terms of tocolytic efficacy or infant outcomes. The finding of an increase in infant deaths in one placebo controlled trial warrants caution. A recent Cochrane review suggests that calcium channel blockers (mainly nifedipine) are associated with better neonatal outcome and fewer maternal side-effects than betamimetics. However, a randomised comparison of nifedipine with placebo is not available. Further well-designed randomised controlled trials of tocolytic therapy are needed. Such trials should incorporate a placebo arm.
[Note: The 24 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]
|
CD008127
|
[
"20163990"
] |
[
"Daclizumab in active relapsing multiple sclerosis (CHOICE study): a phase 2, randomised, double-blind, placebo-controlled, add-on trial with interferon beta."
] |
[
"Daclizumab, a humanised monoclonal antibody, reduced multiple sclerosis disease activity in previous non-randomised studies. We aimed to assess whether daclizumab reduces disease activity in patients with active relapsing multiple sclerosis who are receiving interferon beta treatment.\n We did a phase 2, randomised, double-blind, placebo-controlled study at 51 centres in the USA, Canada, Germany, Italy, and Spain. Patients with active relapsing multiple sclerosis who were taking interferon beta were randomly assigned to receive add-on subcutaneous daclizumab 2 mg/kg every 2 weeks (interferon beta and high-dose daclizumab group), daclizumab 1 mg/kg every 4 weeks (interferon beta and low-dose daclizumab group), or interferon beta and placebo for 24 weeks. The randomisation scheme was generated by Facet Biotech. All patients and assessors were masked to treatment with the exception of Facet Biotech bioanalysts who prepared data for the data safety monitoring board or generated pharmacokinetic or pharmacodynamic data, a drug accountability auditor, and the site pharmacist. The primary endpoint was total number of new or enlarged gadolinium contrast-enhancing lesions measured on brain MRI scans every 4 weeks between weeks 8 and 24. Effects of daclizumab on prespecified subsets of lymphocytes and quantitative T-cell proliferative response were assessed in an exploratory pharmacodynamic substudy. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00109161.\n From May, 2005, to March, 2006, 288 patients were assessed for eligibility, and 230 were randomly assigned to receive interferon beta and high-dose daclizumab (n=75), interferon beta and low-dose daclizumab (n=78), or interferon beta and placebo (n=77). The adjusted mean number of new or enlarged gadolinium contrast-enhancing lesions was 4.75 in the interferon beta and placebo group compared with 1.32 in the interferon beta and high-dose daclizumab group (difference 72%, 95% CI 34% to 88%; p=0.004) and 3.58 in the interferon beta and low-dose daclizumab group (25%, -76% to 68%; p=0.51). In the pharmacodynamic substudy, daclizumab was not associated with significant changes in absolute numbers of T cells, B cells, or natural killer cells, or T-cell proliferative response compared with interferon beta alone. The number of CD56(bright) natural killer cells was seven to eight times higher in both daclizumab groups than in the interferon beta and placebo group (interferon beta and low-dose daclizumab group p=0.002; interferon beta and high-dose daclizumab group p<0.0001). Common adverse events were equally distributed across groups.\n Add-on daclizumab treatment reduced the number of new or enlarged gadolinium contrast-enhancing lesions compared with interferon beta alone and might reduce multiple sclerosis disease activity to a greater extent than interferon beta alone.\n Facet Biotech and Biogen Idec.\n 2010 Elsevier Ltd. All rights reserved."
] |
Daclizumab is well tolerated in combination with interferon beta treated multiple sclerosis population. Comparing with placebo, high-dose daclizumab can significantly decreased the number of new or enlarged gadolinium contrast-enhancing lesions. However, the evidence of recommendation is insufficient. More well-designed RCTs or crossover controlled trials are required to evaluate the efficacy and safety of daclizumab.
|
CD004415
|
[
"12140473",
"12775317",
"18341663",
"17034536",
"16785375",
"8977678",
"19470041",
"12582393",
"19222455",
"18067630",
"18643849",
"18707799",
"19309347",
"20518784",
"19180894",
"14711141",
"19138010",
"20865842",
"11423841",
"16485881",
"17050927",
"18042331",
"18569272",
"19370466",
"12502122",
"10857368",
"16403097",
"16912977",
"10573224",
"20426780",
"15262691",
"11841372",
"11737438",
"14732659",
"16159735",
"17659006",
"15389189",
"18294318",
"19467365",
"19416257",
"17373172",
"16924046",
"15090013",
"14732655",
"15844060",
"8963007",
"9431711",
"12271300",
"12581080",
"18808378",
"14732656",
"17223873",
"17376205",
"10354167",
"18709309",
"16780497",
"20889234",
"17501955",
"15097955",
"7950836",
"18476957",
"12437457",
"16700666",
"8374882",
"15009297",
"14616490",
"19675691",
"12353677",
"20507841",
"16681586"
] |
[
"Photodynamic therapy using topical methyl 5-aminolevulinate compared with cryotherapy for actinic keratosis: A prospective, randomized study.",
"A comparison of photodynamic therapy using topical methyl aminolevulinate (Metvix) with single cycle cryotherapy in patients with actinic keratosis: a prospective, randomized study.",
"Multicentre intraindividual randomized trial of topical methyl aminolaevulinate-photodynamic therapy vs. cryotherapy for multiple actinic keratoses on the extremities.",
"Intraindividual, right-left comparison of topical methyl aminolaevulinate-photodynamic therapy and cryotherapy in subjects with actinic keratoses: a multicentre, randomized controlled study.",
"Comparison of topical methyl aminolevulinate photodynamic therapy with cryotherapy or Fluorouracil for treatment of squamous cell carcinoma in situ: Results of a multicenter randomized trial.",
"Comparison of photodynamic therapy with cryotherapy in the treatment of Bowen's disease.",
"Intraindividual, right-left comparison of topical 5-aminolevulinic acid photodynamic therapy vs. 5% imiquimod cream for actinic keratoses on the upper extremities.",
"Photodynamic therapy with topical methyl aminolevulinate for actinic keratosis: results of a prospective randomized multicenter trial.",
"Optimization of photodynamic therapy with a novel self-adhesive 5-aminolaevulinic acid patch: results of two randomized controlled phase III studies.",
"A randomised study of topical 5% imiquimod vs. topical 5-fluorouracil vs. cryosurgery in immunocompetent patients with actinic keratoses: a comparison of clinical and histological outcomes including 1-year follow-up.",
"Effective photodynamic therapy of actinic keratoses on the head and face with a novel, self-adhesive 5-aminolaevulinic acid patch.",
"Topical methyl-aminolevulinate photodynamic therapy using red light-emitting diode light for treatment of multiple actinic keratoses: A randomized, double-blind, placebo-controlled study.",
"Topical methyl aminolevulinate photodynamic therapy using red light-emitting diode light for multiple actinic keratoses: a randomized study.",
"Photodynamic therapy with BF-200 ALA for the treatment of actinic keratosis: results of a prospective, randomized, double-blind, placebo-controlled phase III study.",
"Treatment of actinic keratoses with sequential use of photodynamic therapy; and imiquimod 5% cream.",
"Short incubation PDT versus 5-FU in treating actinic keratoses.",
"Fractionated illumination improves the outcome in the treatment of precancerous lesions with photodynamic therapy.",
"A randomized, double-blinded, placebo-controlled, multicenter, efficacy and safety study of 3.75% imiquimod cream following cryosurgery for the treatment of actinic keratoses.",
"Photodynamic therapy of actinic keratoses with topical aminolevulinic acid hydrochloride and fluorescent blue light.",
"One-week treatment with 0.5% fluorouracil cream prior to cryosurgery in patients with actinic keratoses: a double-blind, vehicle-controlled, long-term study.",
"Efficacy of 3% diclofenac gel for the treatment of actinic keratoses: a randomized, double-blind, placebo controlled study.",
"Efficacy of imiquimod as an adjunct to cryotherapy for actinic keratoses.",
"Comparison of the efficacy and tolerability of 3% diclofenac sodium gel and 5% imiquimod cream in the treatment of actinic keratosis.",
"Treatment of actinic keratoses on the dorsum of the hands: ALA-PDT versus diclofenac 3% gel followed by ALA-PDT. A placebo-controlled, double-blind, pilot study.",
"Randomized trial evaluating a new 0.5% fluorouracil formulation demonstrates efficacy after 1-, 2-, or 4-week treatment in patients with actinic keratosis.",
"Photodynamic therapy of superficial basal cell carcinoma with 5-aminolevulinic acid with dimethylsulfoxide and ethylendiaminetetraacetic acid: a comparison of two light sources.",
"Imiquimod-induced regression of actinic keratosis is associated with infiltration by T lymphocytes and dendritic cells: a randomized controlled trial.",
"A clinical comparison and long-term follow-up of topical 5-fluorouracil versus laser resurfacing in the treatment of widespread actinic keratoses.",
"Efficacy and safety of photodynamic therapy versus Nd-YAG laser resection in NSCLC with airway obstruction.",
"Photodynamic therapy of multiple actinic keratoses: reduced pain through use of visible light plus water-filtered infrared A compared with light from light-emitting diodes.",
"Effect of a 1-week treatment with 0.5% topical fluorouracil on occurrence of actinic keratosis after cryosurgery: a randomized, vehicle-controlled clinical trial.",
"Topical treatment of actinic keratoses with 3.0% diclofenac in 2.5% hyaluronan gel.",
"Topical 3.0% diclofenac in 2.5% hyaluronan gel in the treatment of actinic keratoses.",
"Photodynamic therapy with aminolevulinic acid topical solution and visible blue light in the treatment of multiple actinic keratoses of the face and scalp: investigator-blinded, phase 3, multicenter trials.",
"A randomized multicenter study to compare two treatment regimens of topical methyl aminolevulinate (Metvix)-PDT in actinic keratosis of the face and scalp.",
"Comparison between 308-nm monochromatic excimer light and narrowband UVB phototherapy (311-313 nm) in the treatment of vitiligo--a multicentre controlled study.",
"Imiquimod 5% cream for the treatment of actinic keratosis: results from a phase III, randomized, double-blind, vehicle-controlled, clinical trial with histology.",
"Continuous activation of PpIX by daylight is as effective as and less painful than conventional photodynamic therapy for actinic keratoses; a randomized, controlled, single-blinded study.",
"Randomized, double-blind, double-dummy, vehicle-controlled study of ingenol mebutate gel 0.025% and 0.05% for actinic keratosis.",
"Photodynamic therapy of actinic keratoses with 8% and 16% methyl aminolaevulinate and home-based daylight exposure: a double-blinded randomized clinical trial.",
"Comparison of 5% 5-fluorouracil cream and 5% imiquimod cream in the management of actinic keratoses on the face and scalp.",
"Facial resurfacing for nonmelanoma skin cancer prophylaxis.",
"Comparative study of the efficacy of combined cryotherapy and intralesional meglumine antimoniate (Glucantime) vs. cryotherapy and intralesional meglumine antimoniate (Glucantime) alone for the treatment of cutaneous leishmaniasis.",
"Photodynamic therapy using topical methyl aminolevulinate vs surgery for nodular basal cell carcinoma: results of a multicenter randomized prospective trial.",
"Randomized, double-blind clinical trial of topical imiquimod 5% with parenteral meglumine antimoniate in the treatment of cutaneous leishmaniasis in Peru.",
"[Cutaneous cryosurgery in family medicine: dimethyl ether-propane spray versus liquid nitrogen].",
"Topical diclofenac/hyaluronic acid gel in the treatment of solar keratoses.",
"Clinical effect of imiquimod 5% cream in the treatment of actinic keratosis.",
"Topical diclofenac in hyaluronan gel for the treatment of solar keratoses.",
"Treatment of actinic keratoses with a novel betulin-based oleogel. A prospective, randomized, comparative pilot study.",
"Photodynamic therapy of multiple nonmelanoma skin cancers with verteporfin and red light-emitting diodes: two-year results evaluating tumor response and cosmetic outcomes.",
"Treatment of post-transplant premalignant skin disease: a randomized intrapatient comparative study of 5-fluorouracil cream and topical photodynamic therapy.",
"Efficacy of local heat therapy by radiofrequency in the treatment of cutaneous leishmaniasis, compared with intralesional injection of meglumine antimoniate.",
"Recalcitrant hand and foot warts successfully treated with photodynamic therapy with topical 5-aminolaevulinic acid: a pilot study.",
"Targeted broadband ultraviolet b phototherapy produces similar responses to targeted narrowband ultraviolet B phototherapy for vitiligo: a randomized, double-blind study.",
"Comparison between the efficacy of photodynamic therapy and topical paromomycin in the treatment of Old World cutaneous leishmaniasis: a placebo-controlled, randomized clinical trial.",
"A phase II placebo-controlled study of photodynamic therapy with topical hypericin and visible light irradiation in the treatment of cutaneous T-cell lymphoma and psoriasis.",
"Vehicle-controlled, randomized, double-blind study to assess safety and efficacy of imiquimod 5% cream applied once daily 3 days per week in one or two courses of treatment of actinic keratoses on the head.",
"Imiquimod 5% cream for the treatment of actinic keratosis: results from two phase III, randomized, double-blind, parallel group, vehicle-controlled trials.",
"Oral cooling (cryotherapy), an effective treatment for the prevention of 5-fluorouracil-induced stomatitis.",
"A phase II dose-ranging study of topical resiquimod to treat actinic keratosis.",
"A randomized, double-blind, vehicle-controlled study to assess 5% imiquimod cream for the treatment of multiple actinic keratoses.",
"Narrow-band ultraviolet B as monotherapy and in combination with topical calcipotriol in the treatment of vitiligo.",
"A randomized clinical trial of two different durations of oral cryotherapy for prevention of 5-fluorouracil-related stomatitis.",
"Cryopreserved and lyophilized cultured epidermal allografts in the treatment of leg ulcers: a pilot study.",
"Short-course therapy with imiquimod 5% cream for solar keratoses: a randomized controlled trial.",
"Photodynamic therapy (PDT) and waterfiltered infrared A (wIRA) in patients with recalcitrant common hand and foot warts.",
"Effective treatment of actinic keratosis with 0.5% fluorouracil cream for 1, 2, or 4 weeks.",
"Results of a randomized, placebo-controlled safety and efficacy study of topical diclofenac 3% gel in organ transplant patients with multiple actinic keratoses.",
"Topical 5-fluorouracil has no additional benefit in treating common warts with cryotherapy: a single-centre, double-blind, randomized, placebo-controlled trial."
] |
[
"Actinic keratoses (AKs) are the most common premalignant tumors. Without treatment, a significant number of patients with AK will experience squamous cell carcinoma. Photodynamic therapy (PDT) using the new highly selective photosensitizer methyl 5-aminolevulinate is a promising new treatment modality for AK.\n We investigated the complete response rates, cosmetic outcome, and patient satisfaction after photodynamic therapy (PDT) using methyl 5-aminolevulinate (Metvix) versus cryotherapy in the treatment of AKs.\n Patients were randomized to receive either cryotherapy with liquid nitrogen spray or PDT using methyl 5-aminolevulinate cream 160 mg/g, 3 hours application time, and red light (75 J/cm(2)).\n Efficacy results from 193 patients with 699 lesions (92% face/scalp and 93% thin/moderately thick) were analyzed. Overall complete response rates after 3 months were 69% for PDT and 75% for cryotherapy. Both treatments gave higher response rates in thin lesions (PDT 75%, cryotherapy 80%). PDT gave better cosmetic results and higher patient satisfaction than cryotherapy.\n PDT using methyl 5-aminolevulinate is an attractive treatment option for patients with AK, with a response rate similar to that of cryotherapy, but with superior cosmetic results and high patient satisfaction.",
"Actinic keratosis (AK) is a very common condition, which has the potential of progressing to squamous cell carcinoma. The present study is a prospective, randomized study comparing the lesion response, cosmetic outcome, patient satisfaction and tolerability of a new treatment modality, photodynamic therapy (PDT), using topical methyl aminolevulinate (Metvix), with the most commonly used standard therapy for AK, cryotherapy.\n A total of 204 patients with clinically diagnosed AK were randomized to either cryotherapy or PDT. The PDT patients were further assigned to an active or placebo group in a random, double-blind manner. Cryotherapy was performed using liquid nitrogen spray in a single freeze-thaw cycle. PDT was performed using 160 mg/g methyl aminolevulinate cream or placebo, a 3-hour application time, red light (570-670 nm) and a total light dose of 75 J/cm(2). PDT was repeated after 7 days. Two sessions of PDT were undertaken, as a previous study had shown a single session had similar efficacy to cryotherapy. Lesion response was assessed clinically after 3 months (complete response or non-complete response).\n The lesion response rate was 91% in the methyl aminolevulinate PDT group, 68% in the cryotherapy group and 30% in the placebo PDT group. Methyl aminolevulinate PDT was statistically significantly better than both cryotherapy and placebo PDT in terms of response rates and cosmetic outcome. Most patients preferred PDT to other treatments.\n PDT with methyl aminolevulinate is an excellent treatment option, particularly for patients with widespread damage or AK lesions in cosmetically sensitive areas.",
"Methyl aminolaevulinate-photodynamic therapy (MAL-PDT) is an effective treatment in facial/scalp actinic keratosis (AK).\n The aims of this study were to compare efficacy, safety, cosmetic outcome and patient preference of MAL-PDT vs. cryotherapy in patients with AK at other locations.\n A multicentre, controlled, randomized, open, intraindividual, right-left comparison was performed. Patients with nonhyperkeratotic AK were treated once with MAL-PDT and cryotherapy on either side of the body. At week 12, lesions showing noncomplete response were retreated. The primary efficacy variable was the lesion response at week 24. Investigator's assessment of cosmetic outcome, patient's preference in terms of cosmetic outcome and a patient preference questionnaire were also analysed at week 24.\n In total, of 121 patients with 1343 lesions (98% located on the extremities and the remainder on the trunk and neck) were included. Both treatments provided a high mean percentage reduction in lesion count at week 24 with significantly higher efficacy for cryotherapy: 78% for MAL-PDT and 88% for cryotherapy (P=0.002, per protocol population). Investigator's assessment of cosmetic outcome was significantly better for MAL-PDT than cryotherapy (P<0.001), 79% of lesions having an excellent cosmetic outcome with MAL-PDT vs. 56% with cryotherapy at week 24. The cosmetic outcome achieved by MAL-PDT compared with cryotherapy was also preferred by patients (50% vs. 22%, respectively, P<0.001), and 59% of patients would prefer to have any new lesions treated with MAL-PDT compared with 25% with cryotherapy (P<0.001). Both treatment regimens were safe and well tolerated.\n MAL-PDT showed inferior efficacy for treatment of non-face/scalp AK compared with cryotherapy. However, both treatments showed high efficacy, and MAL-PDT conveyed the advantages of better cosmesis and higher patient preference.",
"Actinic keratosis (AK), the most common premalignant skin condition, can represent a management challenge. Treatment should not only be effective, but also well tolerated and allow for good cosmesis on typical sun-exposed highly visible body sites.\n The primary objective was to compare the lesion response and subject preference for topical methyl aminolaevulinate (MAL)-photodynamic therapy (PDT) vs. cryotherapy for the treatment of AK.\n In this 24-week, multicentre, randomized, intraindividual (right-left) study, subjects received both one treatment session of MAL-PDT and a double freeze-thaw cryotherapy; the treatments were randomly allocated to either side of the face/scalp. Lesions with a noncomplete response were retreated after 12 weeks. The primary assessments were the subject's overall preference and lesion response at week 24. Secondary assessments included lesion response at week 12, cosmetic outcome, subject and investigator cosmetic outcome preference at week 24, and investigator overall preference at week 24. Skin discomfort and adverse events were also evaluated.\n In total, 119 subjects with 1,501 lesions were included in the study. At week 12, treatment with MAL-PDT resulted in a significantly larger rate of cured lesions relative to cryotherapy (percentage lesion reduction from baseline: 86.9% vs. 76.2%; P < 0.001). At week 24, both treatment groups showed a high rate of cured lesions (89.1% for MAL-PDT vs. 86.1% for cryotherapy; P = 0.20; 95% confidence interval: -1.62 to 7.67). Results for subject and investigator preferences as well as cosmetic outcome favoured MAL-PDT. Both treatment regimens were safe and well tolerated.\n The present study shows that, when treated with both MAL-PDT and cryotherapy, subjects significantly prefer MAL-PDT treatment for AK. MAL-PDT is an attractive treatment option for AK, with comparable efficacy and superior cosmetic outcomes compared with double freeze-thaw cryotherapy.",
"To compare the efficacy, tolerability, and cosmetic outcome of photodynamic therapy (PDT) using topical methyl aminolevulinate with cryotherapy or topical fluorouracil for treatment of squamous cell carcinoma in situ.\n Randomized, placebo-controlled study, with follow-up at 3 and 12 months after last treatment.\n Forty outpatient dermatology centers in 11 European countries.\n Random sample of 225 patients with histologically confirmed squamous cell carcinoma in situ (lesion size, 6-40 mm) and no evidence of progression.\n Treatment with PDT with methyl aminolevulinate (160 mg/g; n = 96) or matching placebo cream (n = 17), cryotherapy (n = 82), or topical fluorouracil (5% cream; n = 30). Methyl aminolevulinate or placebo cream was applied for 3 hours before illumination with broadband red light (75 J/cm2, 570-670 nm). Treatment was repeated 1 week later. Cryotherapy was performed with liquid nitrogen spray. Fluorouracil was applied for 4 weeks. Lesions with a partial response at 3 months were re-treated.\n Clinically verified complete response of lesions; blinded and on-site assessment of cosmetic outcome (4-point rating scale).\n At 12 months, the estimated sustained lesion complete response rate with methyl aminolevulinate PDT was superior to that with cryotherapy (80% vs 67%; odds ratio, 1.77; 95% confidence interval, 1.01-3.12; P = .047), and better than that with fluorouracil (80% vs 69%; odds ratio, 1.64; 95% confidence interval, 0.78-3.45; P = .19). Cosmetic outcome at 3 months was good or excellent in 94% of patients treated with methyl aminolevulinate PDT vs 66% with cryotherapy and 76% with fluorouracil, and was maintained at 12 months.\n Methyl aminolevulinate PDT is an effective treatment option for squamous cell carcinoma in situ, with excellent cosmesis.",
"The efficacy and suitability of photodynamic therapy (PDT) was compared with that of cryotherapy in the treatment of 40 lesions of Bowen's disease. Lesions were randomized to receive either cryotherapy with liquid nitrogen, or PDT using a portable desktop lamp incorporating a 300 W xenon short arc discharge source. A porphyrin precursor, 5-aminolaevulinic acid (5-ALA), was applied topically 4 h before irradiation in the PDT group. Each lesion received 125 J/cm2 at a fluence rate of 70 mW/cm2. All patients were reviewed at 2-monthly intervals and treatments repeated if required. Cryotherapy produced clearance in 10 of 20 lesions after one treatment, the remaining 10 lesions requiring two or three treatment applications. PDT resulted in clearance of 15 of 20 lesions after one treatment and of the remaining five lesions after a second treatment. The probability that a lesion cleared after one treatment was greater with PDT than cryotherapy (P < 0.01). Cryotherapy was associated with ulceration (five of 20), infection (two of 20) and recurrent disease (two of 20); no such complications occurred following PDT. PDT using a non-laser light source and topical 5-ALA appears to be at least as effective as cryotherapy in the treatment of Bowen's disease with fewer adverse effects.",
"Actinic keratoses (AKs) are considered as in situ squamous cell carcinoma. Early and effective treatment is important. Objective To compare the efficacy, cosmetic outcome and patient preference of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) with that of 5% imiquimod (IMIQ) cream in patients with AKs on the dorsa of hands and forearms.\n Subjects received two ALA-PDT treatment sessions and one or two courses of imiquimod (three times per week for 4 weeks each). Treatments were randomly allocated to alternate upper extremities. Assessments included lesion response one and six months after treatment, cosmetic outcome evaluated by the investigators and patients' preference 6 months after treatment. Efficacy end point included the individual AK lesion clearance rate.\n Thirty patients with 256 lesions were included in the study. At the first follow-up, treatment with ALA-PDT resulted in significantly larger rate of cured lesions relative to 5% IMIQ cream (70.16% vs. 18.26%). At the second follow-up both treatments showed a high rate of cured lesions (65.32% for PDT vs. 55.65% for IMIQ cream). Response rates obtained in grade I lesions were higher for both treatments (71.64% for PDT vs. 72.13% for IMIQ), while treatment with PDT resulted in a significant larger rate of cured grade II lesions (57.89% for PDT vs. 37.03 for IMIQ). Difference in cosmetic outcome was not statistically significant. Results for subject preference favoured ALA-PDT.\n Our study shows that ALA-PDT and 5% IMIQ cream are both attractive treatment options for upper extremities AKs with comparable efficacy and cosmetic outcomes.",
"Photodynamic therapy (PDT) is a promising new treatment modality for actinic keratoses. Methyl aminolevulinate (MAL) (Metvix, PhotoCure, Oslo, Norway) leads to selective accumulation of photoactive porphyrins in premalignant skin lesions and makes the lesions susceptible to phototoxic effects on illumination with red light.\n This multicenter, randomized, double-blind study compared complete response rates, cosmetic outcome, and patient satisfaction for PDT with cream containing 160 mg/g MAL or placebo cream in the treatment of actinic keratoses.\n After application of the cream under occlusion for 3 hours, the lesions were illuminated by noncoherent red light (570-670 nm, light dose 75 J/cm(2)). Treatment was repeated after 1 week and response was assessed 3 months later. A total of 80 patients were randomized into the study, 42 in the active and 38 in the placebo group.\n Complete lesion response rate was higher after MAL PDT than placebo, 89% versus 38% per protocol analysis (P =.001). An excellent or good cosmetic outcome was reported in more than 90% of patients treated with MAL.\n In this small study, PDT using topical MAL was a safe and effective treatment for actinic keratoses with excellent cosmetic outcome. It is a promising treatment that could benefit from further study.",
"Photodynamic therapy (PDT) is increasingly used for treatment of actinic keratoses (AKs) but is a cumbersome procedure. A thin self-adhesive patch (PD P 506 A) containing 5-aminolaevulinic acid (5-ALA) was developed to facilitate PDT.\n To investigate efficacy and safety of the patch in comparison with placebo-PDT (superiority design, observer-blinded; study AK 03) and standard therapy, cryosurgery (noninferiority design, open; study AK 04).\n Two separate confirmatory randomized parallel-group phase III studies were set up. In total, 449 patients with up to eight mild to moderate AK study lesions located on the head were treated in 29 German study centres (study AK 03: 103 patients; study AK 04: 346 patients).\n Twelve weeks after treatment, 5-ALA patch-PDT proved to be superior to placebo-PDT (P < 0.001) and cryosurgery (P = 0.007). Efficacy rates on a lesion basis were 82% (AK 03) and 89% (AK 04) for PDT, 77% for cryosurgery and 19% (AK 03) and 29% (AK 04) for placebo-PDT. Local reactions at the treatment site occurred in almost all patients treated with 5-ALA patch-PDT or cryosurgery. Headache was the only side-effect not related to the treatment site which occurred in more than one patient.\n PD P 506 A is an innovative, easy-to-handle 5-ALA patch for PDT of mild to moderate AK lesions. Compared with current PDT procedures, pretreatment (e.g. curettage) is not needed and handling is considerably facilitated. A single PDT treatment results in efficacy rates being statistically significantly superior to placebo and cryosurgery.",
"Actinic keratoses (AK) frequently occur on sun-exposed skin and are considered as in situ squamous cell carcinoma. To date, no treatment algorithm exists for first or second line therapies due to the lack of comparative studies.\n This study compared the initial and 12-month clinical clearance, histological clearance, and cosmetic outcomes of topically applied 5% imiquimod (IMIQ) cream, 5% 5-fluorouracil (5-FU) ointment and cryosurgery for the treatment of AK.\n Patients were randomised to one of the following three treatment groups: one or two courses of cryosurgery (20-40 s per lesion), topical 5-FU (twice daily for 4 weeks), or one or two courses of topical imquimod (three times per week for 4 weeks each).\n Sixty-eight per cent (17/25) of patients treated with cryosurgery, 96% (23/24) of patients treated with 5-FU, and 85% (22/26) of patients treated with IMIQ achieved initial clinical clearance, p = 0.03. The histological clearance rate for cryosurgery was 32% (8/25), 67% (16/24) for 5-FU, and 73% (19/26) in the IMIQ group, p = 0.03. The 12-month follow-up showed a high rate of recurrent and new lesions in the 5-FU and cryosurgery arms. The sustained clearance rate of initially cleared individual lesions was 28% (7/25) for cryosurgery, 54% (13/24) for 5-FU and 73% (19/26) for IMIQ (p < 0.01). Sustained clearance of the total treatment field was 4% (1/25), 33% (8/24), and 73% (19/26) of patients after cryosurgery, 5-FU, and IMIQ, respectively (p < 0.01). The patients in the IMIQ group were judged to have the best cosmetic outcomes (p = 0.0001).\n Imiquimod treatment of AK resulted in superior sustained clearance and cosmetic outcomes compared with cryosurgery and 5-FU. It should be considered as a first line therapy for sustained treatment of AK.",
"Photodynamic therapy (PDT) is increasingly used for the treatment of actinic keratosis (AK).\n To investigate both the efficacy of different application times and the safety of a novel patch (PD P 506 A) containing aminolaevulinic acid in the PDT of mild to moderate AK.\n Applications of PD P 506 A for 0.5, 1, 2 and 4 h were compared in a multicentre, randomized, blinded-observer, parallel-group study. After patch removal, study lesions were illuminated with red light (lambda(em) approximately 630 nm; 37 J/cm(2)). Study lesions were not pretreated (e.g. by curettage) prior to PDT. Efficacy was evaluated 4 and 8 weeks after treatment. Safety and tolerability were determined through laboratory analyses and documentation of both local reactions and adverse events.\n A total of 149 patients were initially enrolled. Of these, 140 patients (520 lesions) completed the study according to protocol. Eight weeks after treatment, 86% of the AK lesions (74% of the patients) treated with 4-h patch application showed complete clearance. The complete clearance rates of lesions (patients) for the 2-, 1- and 0.5-h treatment arms were 73% (47%), 72% (50%) and 51% (24%), respectively. Statistically, the 4-h application was identified as the 'best treatment'. Patients with clearance seemed to experience local reactions to a greater extent than patients without clearance. Local reactions to study treatments did not exceed the expected range.\n The results of this first clinical efficacy study suggest excellent therapeutic outcomes with a single PD P 506 A PDT with a 4-h application.",
"The use of light-emitting diode light offers practical advantages in photodynamic therapy (PDT) with topical methyl-aminolevulinate (MAL) for management of actinic keratoses (AK).\n We sought to evaluate the efficacy of MAL PDT using red light-emitting diode light.\n We conducted a multicenter, double-blind, randomized study. A total of 49 patients with 363 AK lesions had 16.8% MAL cream applied under occlusion for 3 hours, and 47 patients with 360 AK lesions had vehicle cream similarly applied. The lesions were then illuminated (630 nm, light dose 37 J/cm2) with repeated treatment 1 week later. Complete lesion and patient (all lesions showing complete response) response rates were evaluated 3 months after last treatment.\n MAL PDT was superior (P<.0001) to vehicle PDT with respect to lesion complete response (86.2% vs 52.2%, odds ratio 6.9 [95% confidence interval 4.7-10.3]) and patient complete response (59.2% vs 14.9%, odds ratio 13.2 [95% confidence interval 4.1-43.1]).\n The study population may not be representative of all patients with AK.\n MAL PDT using red light-emitting diode light is an appropriate treatment alternative for multiple AK lesions.",
"Photodynamic therapy (PDT) is an effective treatment for actinic keratoses (AKs). Light-emitting diodes (LEDs) offer practical advantages when treating multiple lesions.\n To evaluate the efficacy and tolerability of PDT using a LED and topical methyl aminolevulinate (MAL) for treatment of multiple AKs.\n One hundred thirty-one patients with four to 10 non-pigmented, previously untreated thin or moderately thick AKs on the face or scalp were enrolled in this multicenter, double-blind, randomized, placebo-controlled study. MAL or matching placebo cream was applied to the débrided lesion surface for 3 hours before illumination with noncoherent red light (630 nm, light dose 37 J/cm(2)). Treatment was repeated 1 week later.\n Efficacy was evaluated in 57 patients with 418 lesions treated with MAL PDT and 58 with 414 lesions treated with placebo PDT. Sixteen patients were excluded as protocol violators (not randomized). MAL PDT was superior (p< .001) to placebo PDT in lesion complete response rates (83.3%, 95% confidence interval (CI)=79.3-86.7%, vs 28.7%, 95% CI=24.4-33.4%) and patient complete response rates (all lesions showing complete response; 68.4%, 95% CI=54.8-80.1% vs 6.9%, 95% CI=1.9-16.7%).\n Topical MAL PDT using a LED is an effective treatment for multiple AKs.",
"Photodynamic therapy (PDT) with 5-aminolaevulinic acid (ALA) provides a therapeutic option for the treatment of actinic keratosis (AK). Different strategies are applied to overcome the chemical instability of ALA in solution and to improve skin penetration. A new stable nanoemulsion-based ALA formulation, BF-200 ALA, is currently in clinical development for PDT of AK.\n To evaluate the efficacy and safety of PDT of AK with BF-200 ALA.\n The study was performed as a randomized, multicentre, double-blind, placebo-controlled, interindividual, two-armed trial with BF-200 ALA and placebo. A total of 122 patients with four to eight mild to moderate AK lesions on the face and/or the bald scalp were included in eight German study centres. The efficacy of BF-200 ALA after one and two PDT treatments was evaluated. BF-200 ALA was used in combination with two different light sources under illumination conditions defined by European competent authorities.\n PDT with BF-200 ALA was superior to placebo PDT with respect to patient complete clearance rate (per-protocol group: 64% vs. 11%; P < 0.0001) and lesion complete clearance rate (per-protocol group: 81% vs. 22%) after the last PDT treatment. Statistically significant differences in the patient and lesion complete clearance rates and adverse effect profiles were observed for the two light sources, Aktilite CL128 and PhotoDyn 750, at both time points of assessment. The patient and lesion complete clearance rates after illumination with the Aktilite CL128 were 96% and 99%, respectively.\n BF-200 ALA is a very effective new formulation for the treatment of AK with PDT. Marked differences between the efficacies and adverse effects were observed for the different light sources used. Thus, PDT efficacy is dependent both on the drug and on the characteristics of the light source and the illumination conditions used.",
"Field-directed therapies for actinic keratosis include photodynamic therapy and imiquimod.\n The author designed a randomized, vehicle-controlled, split-face study to explore the safety and efficacy of photodynamic therapy followed by imiquimod.\n The entire face of adults with > or =10 facial actinic keratoses were treated with photodynamic therapy with aminolevulinic acid 20% at baseline and at month 1. At month 2, imiquimod 5% cream was applied to one-half of the face and vehicle to the other half, 2-times-per-week for 16 weeks. Lesion counts were performed at baseline and months 1, 2, 3, 4, 6, and 12; and local skin reactions assessments at months 2, 3, 4, and 6.\n Of 25 participants enrolled, 24 completed the study. Baseline median lesions were 23.5 and 21.5 for the imiquimod- and vehicle-treated sides, respectively. At month 12, median lesion reductions was 89.9% versus 74.5% (P=.0023), respectively. No subject discontinued for an adverse event. Severe local skin reactions occurring in the most participants were erythema (17%) and flaking/scaling/dryness (13%).\n Photodynamic therapy followed by imiquimod was well tolerated and improved reduction of actinic keratoses.",
"The efficacy of photodynamic therapy (PDT) using broad area treatment with 5-aminolevulinic acid (ALA) has not been compared to topical 5-fluorouracil (5-FU) in the treatment of actinic keratoses (AK). The purpose of this study was to compare the efficacy and tolerability of PDT using short incubation time, broad area treatment with ALA plus activation with either blue light or laser light to topical 5-FU in the treatment of AK of the face and scalp. Thirty-six subjects with AK of either the face or scalp were randomized to receive either application of ALA for 1 hour followed by activation with blue light or pulsed dye laser or topical 5-FU. Efficacy was evaluated by grading AK lesions and photoaging signs. Tolerability was assessed by scoring crusting/erosions, erythema and stinging/burning. Treatment with PDT using ALA plus blue light was as effective as topical 5-FU in clearing AK. PDT using ALA plus laser light was the least effective treatment. All treatments made improvements in the signs of photoaging. Both PDT treatments were better tolerated than 5-FU. In conclusion, broad area PDT treatment with ALA plus activation with blue light appears to be as effective as 5-FU in the treatment of AK. ALA plus laser light is somewhat less effective than the above therapies. Efficacy could likely be improved with further study of laser parameters and incubation times.",
"Photodynamic therapy (PDT) is a noninvasive therapy for non-melanoma skin cancer. The aim of this study was comparison of efficacy between fractioned versus single dose illumination in photodynamic therapy (PDT) of actinic keratosis (AK) and Bowen's disease (BD). Fifty-one patients (36 AK and 15 BD) were treated with PDT They were randomly arranged in two treatment groups. Group one included 26 patients (20 AK and 6 BD) that, after five hours of incubation with 20% 5-ALA, were treated with a single illumination of 100 Jcm(-2) at fluence rate of 30 mWcm(-2). Group two included 25 patients (16 AK and 9 BD) that, after 16 hours of incubation with 20% 5-ALA, were treated with two light fractions (50 plus 50 Jcm(-2)) at same fluence rate with dark interval of two hours between fractions. Twenty-four weeks later, a treated area was incubated for four hours again with 5-ALA in order to detect occult areas of abnormal skin with possible remaining tumor tissue. In case of fluorescence, histological examination was performed. In the group one, fluorescence at the end of the session was absent in 19 (73%) or very weak in 7 (27%). Residual tumor was found in 15 (75%) AK and in 4 (66.6%) BD. In the group two, fluorescence at the end of second session was more intense; in one patient (4%) was absent, very weak in 5 (20%) and weak in 19 (76%) of patients. In this group histology revealed remaining tumor tissue in only 2 (12.5%) AK and 2 (22.2%) BD. Among the patients in the first group, the remaining tumor tissue was significantly bigger (p=0.005). The treatment response with clearing of tumor tissue was significantly higher in fractionated illumination than in a single dose illumination group. Fractionated illumination scheme with 16 hours of incubation separated by two hours dark interval significantly improves the therapeutic outcome in tumor eradication.",
"Evaluate cryosurgery followed by 3.75% imiquimod cream to treat actinic keratoses (AK).\n Adults with > or =10 AKs on the face underwent cryosurgery of five to 14 lesions. Subjects with > or =5 lesions remaining were randomized to 3.75% imiquimod or placebo cream applied to the entire face daily for two two-week cycles. Efficacy was assessed through week 26.\n For the cryosurgery/3.75% imiquimod (n=126) and cryosurgery/placebo (n=121) groups, respectively, median total AK reductions were 86.5 and 50 percent, and proportions of subjects with complete clearance were 30.2 and 3.3 percent (P < 0.0001, both). Analyzing cryosurgery-treated lesions only, median reductions were 100 and 80 percent (P = 0.0008), and subject complete clearance rates were 59.5% and 29.8% (P < 0.001), respectively. Only one subject discontinued for a treatment-related adverse event (cryosurgery/3.75% imiquimod group).\n Cryosurgery was performed per usual study center practice and not standardized.\n A short, cyclical treatment course of field-directed daily 3.75% imiquimod cream following lesion-directed cryosurgery was well tolerated and provided additional therapeutic benefits to cryosurgery alone.",
"Aminolevulinic acid hydrochloride (ALA, Levulan) applied topically to actinic keratoses (AKs) leads to accumulation of the photosensitizer protoporphyrin IX, which, when activated by exposure to light, eradicates AKs.\n We examined the safety and efficacy of photodynamic therapy using topical 20% ALA in a solution formulation and varying blue light doses to treat multiple AKs on the face and scalp.\n This is a multicenter, investigator-blinded, randomized, vehicle-controlled study.\n Thirty-six patients with clinically typical AKs were treated with 20% ALA; 14 to 18 hours later, they were irradiated with a nonlaser fluorescent blue light source. With the optimal light dose of 10 J/cm(2), 88% of the AKs completely cleared 8 weeks after a single photodynamic treatment, compared with 6% after treatment with vehicle and light.\n Topical ALA PDT using a nonlaser, blue light source is an effective treatment for multiple AKs.",
"Topical fluorouracil is currently approved for the treatment of actinic keratosis (AK) and is often used prior to or following cryosurgery as interval therapy in patients with severe AK lesions. No randomized, controlled studies are available to confirm anecdotal evidence suggesting pretreatment with fluorouracil is beneficial. This prospective, randomized, double-blind, vehicle-controlled study evaluated the effect of pretreatment with 0.5% fluorouracil cream (FC; Carac) or a vehicle cream (VC) once daily for 7 days to the face plus scalp, ears, neck, and/or lips in patients with > or = 5 visible or palpable AKs on the face prior to cryosurgery. Efficacy was determined by evaluating AK reduction and clearance (complete lack of AK lesions in the treatment area) at 4 weeks follow-up. Statistically significant decreases from baseline number of AKs were observed on all treatment areas in both groups. However, the mean number of facial AKs was significantly lower in the FC group at each treatment cycle (p = .011). No serious adverse events were considered related to treatment.",
"Actinic keratoses (AKs) are premalignant skin lesions caused by excessive sun exposure.\n To explore the therapeutic efficacy of 3% diclofenac in 2.5% hyaluronan gel in the topical treatment of AK.\n Sixty-four lesions in 20 patients were evaluated. They were randomized to receive either the active treatment, 3% diclofenac in 2.5% hyaluronan gel or placebo, which consisted of the inactive gel vehicle, hyaluronan for a period of three months. The collected data were analyzed by using Student t- tests.\n There was a reduction in the lesion size in 64.7% of diclofenac-treated lesions and 34.3% of control lesions during the three-month course of treatment. Only 9.3% of the lesions in the diclofenac group were completely cleared during three months of treatment. During the treatment, no significant side-effect was observed in both groups.\n Considering the malignant potential of actinic keratoses and the importance of clearing them to prevent their transformation to squamous cell carcinoma, the efficacy of diclofenac gel seen in our study seems to be low. This treatment may be useful for patients who do not tolerate other, more effective kinds of treatment for actinic keratoses.",
"Cryotherapy is the standard of care for clinically apparent (target) actinic keratoses (AKs). Topical imiquimod may reduce initially inapparent or subclinical AKs.\n We evaluated the potential of topical imiquimod to decrease subclinical AKs after cryotherapy of target AKs.\n A randomized trial of imiquimod or vehicle twice weekly for 8 weeks following 3- to 5-second cryotherapy of target AKs within a 50 cm(2) field at the face or scalp was conducted. Efficacy outcomes included clearance of target, subclinical, and total AKs and proportions clear of AKs. Subjects with residual AKs were offered cryotherapy and open-label imiquimod twice weekly for 8 weeks.\n Sixty-three subjects completed the randomized phase. At 12 weeks, target AK clearance was similar for imiquimod and vehicle (79% vs 76%), but fewer total AKs were noted for imiquimod (78 vs 116). This was due to a progressive reduction in subclinical AKs with imiquimod compared with a progressive increase with vehicle. More subjects treated with imiquimod achieved clearance of subclinical (58% vs 34%; p = .06) and total (23% vs 9%; p = .21) AKs.\n Imiquimod postcryotherapy may increase clearance of subclinical and total AKs and proportions of subjects clear at 3 months. These findings require confirmation in larger controlled trials powered for statistical significance.",
"Topical diclofenac and imiquimod have been reported to be effective in the treatment of actinic keratosis, but a study to compare these two drugs has not been reported yet.\n To compare the efficacy and safety of topical 3% diclofenac gel plus hyaluronic acid and 5% imiquimod cream in the treatment of actinic keratosis.\n Forty-nine patients with actinic keratosis were enrolled in this randomized comparative open-label study. Twenty-four patients applied 3% diclofenac gel once a daily to their lesions, while the other 25 patients were treated with a 5% imiquimod cream three times a week for 12 weeks. Patients were examined before treatment and every month of the treatment. Assessments were made by investigators according to the Investigator and the Patient Global Improvement Indices (IGII) and (PGII).\n According to the IGII results, a complete response was observed in 12% of the diclofenac group and 22% of the imiquimod group. For the PGII scores, a complete response was observed in 28% of the diclofenac group and 23% of the imiquimod group. There were no significant differences between the two groups (p > 0.05). Both treatments were well tolerated, with most adverse events related to skin.\n The two drugs were found to be equally effective and safe in the treatment of actinic keratosis but complete remission was very low. Therefore, topical treatments with these two drugs were not seen to be completely effective, and combined therapies and further studies are needed.",
"Actinic keratoses (AK) are sun-induced epithelial skin lesions, which are at risk to progress to squamous cell carcinoma. One of the treatments of AK is photodynamic therapy (PDT), which often has to be repeated. Another treatment for these lesions is diclofenac 3% gel. Although both treatments have shown to be effective, they have never been studied together.\n To investigate whether a pre-treatment of AK on the dorsum of the hands with diclofenac 3% gel improves the efficacy of PDT.\n In this placebo-controlled, randomized, double-blind, pilot study with 10 patients, both hands were pre-treated--one with diclofenac gel and the other with placebo gel--and then the hands were treated with ALA-PDT. Total lesion number scores, total thickness scores and global improvement scores were used to assess efficacy. Pain scores were recorded during PDT.\n In both groups, the number of lesions significantly decreased. At 12 months' follow-up, significantly fewer AK were seen in the diclofenac group. Total lesion thickness scores decreased significantly in both groups. Pain during PDT was greater in the diclofenac group.\n Both treatments are effective in treating AK. A pre-treatment with diclofenac gel seems to result in fewer AK at 12 months' follow-up, compared to placebo. Side effects were worse when using the active drug.",
"The efficacy and safety of a new 0.5% fluorouracil topical cream were compared with vehicle control for the treatment of actinic keratosis (AK). Active treatment applied once daily for 1, 2, or 4 weeks was more effective than vehicle control in achieving reduction from baseline in lesion counts and lesion clearance. Active treatment also resulted in significantly better global assessments of overall improvement. Treatment was effective regardless of the number of baseline lesions. Although longer treatment duration correlated with greater efficacy, treatment for 1, 2, or 4 weeks was effective. This new microsphere-based fluorouracil formulation was generally well tolerated; adverse events were primarily limited to facial irritation that resolved quickly after treatment. This new treatment provides a safe alternative to the topical fluorouracil formulations currently available for the 1-, 2-, or 4-week treatment of AK.",
"The aim of this prospective randomized study was to compare the clinical and cosmetic outcome of superficial basal cell carcinomas (BCC), using either laser or broadband halogen light, in photodynamic therapy with topical 5-aminolevulinic acid (ALA). A total of 83 patients with 245 superficial BCC were included in the study. Standard treatment involved 15 min of local pretreatment with 99% dimethylsulfoxide (DMSO) before topical application of 20% ALA with DMSO (2%) and ethylendiaminetetraacetic acid (2%) as cofactors for 3 h before light exposure with either laser or a broadband lamp (BL). A complete response was achieved in 95 lesions (86%) in the laser group and 110 lesions (82%) in the BL group 6 months after treatment. Of these, 80 lesions (84%) in the laser group and 101 lesions (92%) in the lamp group were independently evaluated to have an excellent or good cosmetic post-treatment score. No serious adverse events were reported. This study shows that there is no statistical significant difference in cure the rate (P = 0.49) and the cosmetic outcome (P = 0.075) with topical application of a modified ALA-cream between light exposure from a simple BL with continuous spectrum (570-740 nm) or from a red-light laser (monochromatic 630 nm). Cost and safety are further elements in favor of the BL in this setting.",
"Imiquimod 5% cream is a topically applied immune response modifier that has been shown to give effective treatment of actinic keratosis (AK). The therapeutic effects of imiquimod are likely to involve the provocation of a cutaneous immune response against abnormal cells, an assumption based on a strong correlation between complete clearance rates and the severity of the local skin reactions (erythema, oedema, erosion/ulceration, weeping/exudation and scabbing/crusting); however, no clinical studies have conclusively proved this mechanism.\n To determine the nature of cellular infiltrates induced by the application of imiquimod to AK lesions and to study cells involved in the cutaneous immune response.\n Eighteen patients participated in this phase I, randomized, double-blind, parallel group, vehicle-controlled study. Enrolled patients were randomized in a 2 : 1 ratio to receive imiquimod cream or vehicle cream and applied study cream to five lesions on the scalp, forearm or upper trunk once daily, three days per week for up to 16 weeks. Each patient had punch biopsies of two distinct AK lesions: a lesion was biopsied before treatment to obtain baseline biomarker levels, and a different lesion was biopsied after 2 weeks of treatment. Biopsy specimens were examined using routine and immunohistochemical staining.\n The imiquimod group showed statistically significant increases from baseline to week 2 in tissue biomarker levels for CD3, CD4, CD8, CD11c, CD86/CD11c, CD68, HLA-DR and TUNEL. No significant differences were seen for the vehicle group. Complete clearance of all treated AK lesions was achieved in five of 11 (45%) imiquimod patients and in none of six vehicle patients.\n Imiquimod stimulates a cutaneous immune response characterized by increases in activated dendritic cells and CD4+ and CD8+ T cells.",
"Many treatment modalities exist for actinic keratoses (AK). Topical 5-fluorouracil (5-FU) has been one of the standard treatments. Laser resurfacing is a more recent treatment option. In the literature prospective randomized studies comparing these treatments are lacking.\n Prospective randomized study to compare topical 5-FU with Er:YAG laser resurfacing. Fifty-five patients with multiple AK on the scalp and or the face were included. Clinical and histopathological evaluation took place at 3, 6, and 12 months after treatment.\n At 3, 6, and 12 months after treatment, there were significantly less recurrences in the laser group compared to the group of patients treated with 5-FU. Side effects did occur more frequently in the laser group, especially erythema and hypopigmentation.\n Compared to treatment with topical 5-FU, Er:YAG laser resurfacing is more effective regarding recurrence rates. Although significantly more side effects occur, laser resurfacing is a useful therapeutic option especially in patients with widespread AK.\n (c) 2006 Wiley-Liss, Inc.",
"A prospective controlled randomized trial was performed in order to assess the effectiveness and safety of photodynamic therapy versus laser resection in 31 patients with partial or complete tracheobronchial obstruction due to inoperable non-small cell lung cancer. Fourteen patients received dihaematoporphyrin ether and argon dye laser photoradiation, and 17 patients received Nd-YAG laser resection. Endoluminal obstruction of >75% was found in 77.4% of the patients. Among the symptoms, cough was more severe in the Nd-YAG group (p=0.02). Patients in both groups experienced symptomatic relief after treatment (p=0.003). Patients in the photodynamic therapy (PDT) group showed a significantly longer time until treatment failure (p=0.03) and longer median survival (p=0.007). Bronchitis and photosensitization (both in the PDT group) were the most common adverse effects. There was one death, probably related to treatment, in the PDT group. Photodynamic therapy and neodymium-yttrium aluminium garnet laser resection showed similar effectiveness and safety in the palliation of symptoms. The more prolonged survival in the photodynamic therapy group may have been due to differences in tumour stage between the groups. The degree of obstruction improved after treatment in both groups. In conclusion, photodynamic therapy is a valid method of palliation in partially or totally obstructing non-small cell lung carcinoma.",
"Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is an effective treatment for multiple actinic keratoses (AKs). Pain, however, is a major side-effect.\n To compare pain intensity, efficacy, safety and cosmetic outcome of MAL PDT with two different light sources in an investigator-initiated, randomized, double-blind study.\n Eighty patients with multiple AKs grade I-II were assigned to two groups: group 1, MAL PDT with visible light and water-filtered infrared A (VIS+wIRA); group 2, MAL PDT with light from light-emitting diodes (LEDs), with a further division into two subgroups: A, no spray cooling; B, spray cooling on demand. MAL was applied 3 h before light treatment. Pain was assessed before, during and after PDT. Efficacy, side-effects, cosmetic outcome and patient satisfaction were documented after 2 weeks and 3, 6 and 12 months. Where necessary, treatment was repeated after 3 months.\n Seventy-six of the 80 patients receiving MAL PDT completed the study. Patient assessment showed high efficacy, very good cosmetic outcome and high patient satisfaction. The efficacy of treatment was better in the group of patients without spray cooling (P=0·00022 at 3 months, P=0·0068 at 6 months) and showed no significant differences between VIS+wIRA and LED. VIS+wIRA was significantly less painful than LED: the median of maximum pain was lower in the VIS+wIRA group than in the LED group for PDT without spray cooling. Pain duration and severity assessed retrospectively were less with VIS+wIRA than with LED, irrespective of cooling.\n All treatments showed high efficacy with good cosmetic outcome and high patient satisfaction. Efficacy of treatment was better without spray cooling. VIS+wIRA PDT was less painful than LED PDT for PDT without spray cooling.\n © 2010 The Authors. Journal Compilation © 2010 British Association of Dermatologists.",
"No long-term randomized controlled clinical trial has compared the efficacy of cryosurgery alone vs cryosurgery following fluorouracil applications for the treatment of actinic keratosis.\n To determine the 6-month outcome of a 1-week course of 0.5% fluorouracil followed by cryosurgery.\n Prospective, multicenter, randomized, double-blind, vehicle-controlled clinical trial performed in community and academic outpatient clinics.\n A total of 144 patients with 5 or more visible or palpable actinic keratoses on the face.\n Topical 0.5% fluorouracil or vehicle once daily for 7 days. At the 4-week follow-up visit, residual lesions were treated with cryosurgery.\n Reduction in facial actinic keratoses from baseline to 4 weeks and 6 months.\n At 4 weeks, mean actinic keratosis lesion count was reduced by 62.4% in the 0.5% fluorouracil group vs 28.8% in the vehicle group (P<.001), and complete clearance was achieved in 16.7% of patients in the 0.5% fluorouracil group vs 0% of those in the vehicle group (P<.001). At 6 months, mean lesion count was reduced by 67.0% in the 0.5% fluorouracil plus cryosurgery group vs 45.6% in the vehicle plus cryosurgery group (P =.01), and significantly more patients in the 0.5% fluorouracil plus cryosurgery group than in the vehicle plus cryosurgery group had complete clearance (30% vs 7.7%; P<.001).\n A 1-week course of topical 0.5% fluorouracil before cryosurgery is significantly more effective in reducing patients' numbers of actinic keratosis lesions 6 months after treatment than cryosurgery alone. The high occurrence rate of actinic keratosis lesions at 6 months suggests a need for follow-up.",
"Actinic keratoses (AKs) are premalignant skin lesions, which, if left untreated, can develop into squamous cell carcinoma. Current treatments for AKs are destructive and are often associated with significant adverse events. The development of an effective and well-tolerated topical treatment for AK is desirable.\n To evaluate the efficacy and safety of 3.0% diclofenac in 2.5% hyaluronan gel as a treatment for AK.\n This was a multicentre, double-blind, placebo-controlled study in which 195 patients with at least five AKs in up to three designated treatment blocks were randomized to four treatment groups. Patients randomized into the active treatment groups A30 (n = 49) and A60 (n = 48) received topical treatment with 3.0% diclofenac in 2.5% hyaluronan gel 0.5 g twice daily for 30 or 60 days, respectively. Patients in the placebo (vehicle gel) groups V30 (n = 49) and V60 (n = 49) received topical treatment with 2.5% hyaluronan gel 0.5 g twice daily for 30 or 60 days, respectively. Treatment efficacy was assessed by target and cumulative lesion number scores (TLNS and CLNS, respectively) and lesion total thickness score (TTS). Investigator and patient global improvement indices (IGII and PGII) were also used to rate overall improvement.\n Compared with placebo, significantly more patients given active treatment for 60 days had TLNS = 0 (33% vs. 10%, P < 0.05; an improvement of 64% compared with 34% with placebo), CLNS = 0 (31% vs. 8%, P < 0.05; an improvement of 54% compared with 23% with placebo) and TTS = 0 (25% vs. 6%, P < 0.05; an improvement of 59% compared with 31% with placebo). The IGII and PGII scores were also significantly better when active treatment was compared with placebo (P < 0.05). Both treatments were generally well tolerated and the incidence of the most common adverse events was similar between groups.\n Treatment with 3.0% diclofenac in 2.5% hyaluronan gel was effective when used for 60 days and was well tolerated in patients with AK.",
"Actinic keratoses (AKs) are epidermal skin lesions with the potential to develop into invasive squamous cell carcinoma (SCC). Treatment at an early stage may prevent development of SCC. Current treatment options are highly destructive and associated with significant side-effects. Early studies with topical diclofenac were encouraging and led to its evaluation for the treatment of actinic keratosis. Previous studies have demonstrated that 3% diclofenac in 2.5% hyaluronan gel is effective and well tolerated in the treatment of AK. The present study was designed to further explore the therapeutic potential of this gel.\n This randomized, double-blind, placebo-controlled trial involved outpatients with a diagnosis of five or more AK lesions contained in one to three 5 cm(2) blocks. Patients received either active treatment (3% diclofenac gel in 2.5% hyaluronan gel) or inactive gel vehicle (hyaluronan) as placebo (0.5 g b.i.d. in each 5 cm(2) treatment area for 90 days). Assessments included the Target Lesion Number Score (TLNS), Cumulative Lesion Number Score (CLNS), and Global Improvement Indices rated separately by both the investigator (IGII) and patient (PGII).\n Results obtained from 96 patients at follow up (30 days after end of treatment) indicated that a significantly higher proportion of patients who received active treatment had a TLNS = 0 compared to the placebo group (50% vs. 20%; P < 0.001). There was also a significant difference between the two groups in CLNS, with 47% of patients in the active treatment group having a CLNS = 0 compared with only 19% in the placebo group (P < 0.001). The proportion of patients with an IGII score of 4 (completely improved) at follow-up was 47% in the active treatment group compared with only 19% in the placebo group (P < 0.001); for PGII these values were 41% vs. 17%, P < 0.001. Both treatments were well tolerated, with most adverse events related to the skin.\n Topical 3% diclofenac in 2.5% hyaluronan gel was effective and well tolerated for the treatment of AK.",
"To determine the safety and efficacy of photodynamic therapy (PDT) using 20% wt/vol aminolevulinic acid hydrochloride (hereinafter \"ALA\") and visible blue light for the treatment of multiple actinic keratoses of the face and scalp.\n Randomized, placebo-controlled, uneven parallel-group study.\n Patients (N = 243) were randomized to receive vehicle or ALA followed within 14 to 18 hours by PDT. Follow-up visits occurred 24 hours and 1, 4, 8, and 12 weeks following PDT. Target lesions remaining at week 8 were re-treated.\n Clinical response based on lesion clearing by week 8.\n Most patients in both groups had 4 to 7 lesions. Complete response rates for patients with 75% or more of the treated lesions clearing at weeks 8 and 12 were 77% (128/166) and 89% (133/149), respectively, for the drug group and 18% (10/55) and 13% (7/52), respectively, for the vehicle group (P<.001, Cochran-Mantel-Haenszel general association test). The 95% confidence interval for the difference in response rates at week 8 was 46.9% to 71.0% and at week 12, 65.3% to 86.3%. The week 12 response rate includes 30% of patients who received a second treatment. Most patients experienced erythema and edema at the treated sites, which resolved or improved within 1 to 4 weeks after therapy, and stinging or burning during light treatment, which decreased or resolved by 24 hours after light treatment.\n Findings indicate that topical ALA PDT is an effective and safe treatment for multiple actinic keratoses of the face and scalp.",
"Photodynamic therapy (PDT) with topical methyl aminolevulinate (MAL) administered in two treatment sessions separated by 1 week is an effective treatment for actinic keratoses. This open prospective study compared the efficacy and safety of MAL-PDT given as a single treatment with two treatments of MAL-PDT 1 week apart. Two hundred and eleven patients with 413 thin to moderately thick actinic keratoses were randomized to either a single treatment with PDT using topical MAL (regimen I; n=105) or two treatments 1 week apart (regimen II; n=106). Each treatment involved surface debridement, application of Metvix cream (160 mg/g) for 3 h, followed by illumination with red light using a light-emitting diode system (peak wavelength 634+/-3 nm, light dose 37 J/cm2). Thirty-seven lesions (19%) with a non-complete response 3 months after a single treatment were re-treated. All patients were followed up 3 months after the last treatment. A total of 400 lesions, 198 initially treated once and 202 treated twice, were evaluable. Complete response rate for thin lesions after a single treatment was 93% (95% CI=87-97%), which was similar to 89% (82-96%) after repeated treatment. Response rates were lower after single treatment of thicker lesions (70% (60-78%) vs 84% (77-91%)), but improved after repeated treatment (88% (82-94%)). The conclusion of this study is that single treatment with topical MAL-PDT is effective for thin actinic keratosis lesions; however, repeated treatment is recommended for thicker or non-responding lesions.",
"Vitiligo is an acquired pigmentary disorder characterized by areas of depigmented skin resulting from loss of epidermal melanocytes. Recently, it has been shown that narrowband ultraviolet B (NB-UVB) phototherapy may be more effective than psoralen and ultraviolet A (PUVA) photochemotherapy in treating vitiligo, and that 308-nm monochromatic excimer light (MEL) may present some advantages as compared to NB-UVB for the treatment of vitiligo. AIM The aim of this study was to compare the effectiveness of NB-UVB phototherapy and 308-nm MEL in vitiligo patients.\n The study was done in a randomized, investigator-blinded and half-side comparison design. Twenty-one subjects with symmetrical vitiligo lesions were enrolled in this study. Vitiligo lesions on one body side were treated twice weekly for 6 months with 308-nm MEL, while NB-UVB phototherapy was used to treat lesions on the opposite side.\n At the end of the study six lesions (37.5%) treated with 308-nm MEL and only one lesion (6%) treated with NB-UVB achieved an excellent repigmentation (score 4) while four lesions (25%) treated with 308-nm MEL and five lesions (31%) treated with NB-UVB showed a good repigmentation (score 3).\n It appears that 308-nm MEL is more effective than NB-UVB in treating vitiligo lesions and it induces repigmentation more rapidly.",
"Increasing evidence suggests imiquimod may be a safe therapeutic option for the treatment of actinic keratosis (AK). The diagnosis and assessment of most AK lesions is made clinically, without histologic confirmation.\n A phase III, randomized, double-blind, parallel group, vehicle-controlled study evaluated the efficacy of imiquimod 5% cream compared with vehicle in the treatment of AK lesions on the face and balding scalp including pretreatment and posttreatment biopsy specimens.\n A total of 286 patients at 18 centers in 6 European countries with histologically confirmed AK were randomized to either imiquimod 5% cream or vehicle cream. Study cream was applied once per day, 3 days per week, for 16 weeks. Clearance of AK lesions was clinically and histologically assessed at an 8-week posttreatment visit.\n The complete clearance rate for the imiquimod group was 57.1% versus 2.2% for the vehicle group (P <.001). The partial clearance rate (> or =75% reduction in baseline lesions) for the imiquimod group was 72.1% versus 4.3% for the vehicle group (P <.001). The most common side effects were erythema, scabbing/crusting, and erosions/ulceration. For the imiquimod group the incidence of severe erythema, scabbing/crusting, or erosions/ulceration was 30.6%, 29.9%, and 10.2%, respectively.\n Imiquimod 5% cream used 3 times per week for 16 weeks is an effective treatment for AK. Clinical clearance was established by both clinical observation and histologic analysis.",
"Photodynamic therapy (PDT) is a highly effective treatment for actinic keratoses (AK); however, it is time consuming and often painful for the patient. Daylight-PDT would make the treatment independent of the clinic and less painful due to the continuous activation of small amounts of porphyrins during its formation.\n The objective of this randomized controlled study was to compare response rates and adverse effects after methyl aminolevulinate (MAL)-PDT using conventional red light-emitting diode (LED) light vs. daylight.\n Twenty-nine patients with AK of the face and scalp were treated with MAL-PDT in two symmetrical areas. One area was illuminated by red LED light (37 J cm(-2)) after 3-h incubation with MAL under occlusive dressing. The other area was treated with daylight for 2.5 h after the MAL cream had been under occlusion for half an hour.\n We found no significant difference in the treatment effect between the two treatments (P = 0.13), with a reduction of AK lesions of 79% in the daylight area compared with 71% in the LED area. Treatment response in the daylight area did not depend on the intensity of the daylight. Illumination with LED was more painful than daylight (P < 0.0001). Erythema and crusting occurred after both treatments and were similar in the two areas.\n PDT of AK by continuous activation of porphyrins by daylight proved to be as effective as conventional PDT. PDT using daylight activation will make the treatment of these extremely common premalignant tumours more time and cost effective, and more convenient for the patient.",
"There is a need for improved medical approaches to the treatment of actinic keratosis. Ingenol mebutate, a diterpene ester extracted and purified from the plant Euphorbia peplus, is being evaluated as a topical therapy for actinic keratosis.\n Assess the efficacy and safety of ingenol mebutate (formerly PEP005) gel at 3 dosing regimens for the treatment of actinic keratosis.\n Patients with non-facial actinic keratoses applied vehicle gel for 3 days, ingenol mebutate gel, 0.025% for 3 days, or ingenol mebutate gel, 0.05% for 2 or 3 days, with an 8-week follow-up period.\n All 3 active treatments were significantly more effective than vehicle at clearing actinic keratosis lesions, with a dose response observed. The partial clearance rate (primary efficacy end point) for patients treated with ingenol mebutate gel ranged from 56.0% to 75.4% compared with 21.7% for vehicle gel (P = .0002 to P < .0001 vs vehicle). The complete clearance rate was also significantly higher (P < or = .0006) for patients in the ingenol mebutate gel treatment groups (range: 40.0% to 54.4%) compared with vehicle (11.7%), as was the baseline clearance rate (range: 42.0% to 57.9% for ingenol mebutate gel compared with 13.3% for vehicle, P < .0001 to .0007 vs vehicle). The median percentage reduction in baseline actinic keratosis lesions for patients treated with ingenol mebutate gel ranged from 75% to 100% compared with 0% for vehicle gel (P < .0001 vs vehicle). Active treatment was well tolerated at all dosages. The mechanism of action of this agent is the localized induction of necrosis followed by a transient inflammatory response, and this was manifested in most patients as transient local skin responses consisting primarily of erythema, flaking/scaling, and crusting. There was no evidence of treatment-related scarring.\n Local skin responses may have suggested active treatment to investigators.\n Short-course, field-directed therapy with ingenol mebutate gel for actinic keratoses on non-facial sites seems to be effective with a favorable safety profile and potential benefits over topical agents that require a more prolonged course of treatment.",
"Photodynamic therapy (PDT) is an effective but time-consuming and often painful treatment for actinic keratosis (AK). Home-based daylight-PDT has the potential to facilitate treatment procedure and to reduce associated pain due to continuous activation of small amounts of porphyrins. Moreover, a reduced methyl aminolaevulinate (MAL) concentration may reduce associated inflammation, making the treatment more tolerable for the patients.\n To compare response rates and adverse effects after PDT using conventional 16% and 8% MAL with home-based daylight exposure in treatment of AK.\n Thirty patients with mostly thin-grade AK of the face or scalp were treated with 16% and 8% MAL-PDT in two symmetrical areas after application of sunscreen. Immediately after, patients left the hospital with instructions to spend the remaining day outside at home in daylight. Patients scored pain during treatment and light exposure was monitored with an electronic wristwatch dosimeter.\n The complete response rate after 3 months was 76.9% for 16% MAL and 79.5% for 8% MAL (P = 0.37). Patients spent a mean of 244 min outdoors and received a mean effective light dose of 30 J cm(-2). Light doses of 8-70 J cm(-2) induced similar response rates (P = 0.25). Patients experienced mild to moderate pain during daylight exposure (mean maximal pain score of 3.7). No differences in pain scores and erythema were seen between the areas treated with 16% MAL and with 8% MAL.\n Home-based daylight-mediated MAL-PDT was an effective and well-tolerated treatment for AK. No differences in response rates or adverse events were found between the areas treated with 16% MAL and with 8% MAL.",
"It is timely to compare the efficacy and tolerability of 2 actinic keratosis (AK) therapies--5% 5-fluorouracil (5-FU) cream and imiquimod cream. Thirty-six patients with 4 or more AKs were randomly assigned to receive 5% 5-FU cream twice daily for 2 to 4 weeks or 5% imiquimod cream twice weekly for 16 weeks. Five percent 5-FU was more effective than imiquimod in exposing what were presumed to be subclinical AKs, reducing the final AK count (total AK count declined during the 24-week study by 94% vs. 66%, P < .05), achieving complete clearance (incidence of 84% vs. 24% by week 24, P < .01), and achieving clearance rapidly. Tolerability was similar except for erythema, which was initially significantly higher with 5-FU than imiquimod but resolved rapidly and was significantly lower than imiquimod by week 16. Five percent 5-FU remains the gold standard field therapy for AKs.",
"To determine the effect of facial skin resurfacing for treatment of actinic keratoses (AKs) and prophylaxis against new primary basal and squamous cell carcinomas in individuals with previous nonmelanoma skin cancer (NMSC) or severe photodamage.\n Randomized, prospective 5-year trial.\n Dermatology and otolaryngology clinics of a Veterans Affairs hospital.\n Thirty-four patients with a history of facial or scalp AKs or basal or squamous cell carcinoma were enrolled. Five of 7 eligible patients who declined study-related treatment were used as controls. Twenty-seven patients were randomized to 3 treatment arms; 3 patients were discontinued from the study.\n Carbon dioxide laser resurfacing, 30% trichloroacetic acid peel, or 5% fluorouracil cream applied twice daily for 3 weeks.\n Reduction in the number of AKs was measured 3 months after treatment. The incidence of new NMSC in treated areas was assessed between January 1, 2001, and June 30, 2005. Times from baseline to diagnosis of first skin cancer were compared between the treatment and control groups.\n Treatment with fluorouracil, trichloroacetic acid, or carbon dioxide laser resulted in an 83% to 92% reduction in AKs (P< or =.03), a lower incidence of NMSC compared with the control group (P<.001), and a trend toward longer time to development of new skin cancer compared with the control group (P=.07). However, no significant differences were noted among the treatment groups.\n All 3 modalities demonstrated benefit for AK reduction and skin cancer prophylaxis compared with controls and warrant further study in a larger trial.",
"Cutaneous leishmaniasis (CL) is a parasitic disease caused by Leishmania species. There is a need for more effective and less time-consuming therapeutic methods for this condition.\n To evaluate the efficacy of combined cryotherapy and intralesional meglumine antimoniate (MA) (Glucantime, Specia, Paris, France) for the treatment of CL.\n Patients were divided into three groups: Group 1, 100 patients with 149 lesions were treated with cryotherapy plus intralesional MA; Group 2, 200 patients with 230 lesions were treated with cryotherapy; Group 3, 100 patients with 160 lesions were treated with intralesional MA. These groups were followed for 6 months after the end of treatment.\n The results showed complete cure in 90.9% of cases in Group 1, 57.15% of cases in Group 2, and 55.63% of cases in Group 3. The difference between Group 1 and the other groups was statistically significant (P < 0.05).\n Combined cryotherapy and intralesional MA is more effective than either cryotherapy or intralesional MA alone for the treatment of CL.",
"Photodynamic therapy (PDT) is increasingly used as a noninvasive treatment for nodular basal cell carcinoma (BCC), without a sound evidence base.\n To compare topical PDT, with the use of the sensitizer methyl aminolevulinate, and standard excision surgery in nodular BCC.\n Prospective, randomized study.\n University dermatology departments.\n A total of 101 adults with previously untreated nodular BCC.\n Patients received methyl aminolevulinate PDT (n = 52) or surgery (n = 49). The PDT was given twice, 7 days apart, with methyl aminolevulinate cream (160 mg/g) and 75 J/cm(2) red light (570-670 nm). Thirteen patients with a noncomplete response to PDT at 3 months (24% lesions) were retreated.\n Primary end point was clinically assessed lesion clearance at 3 months after treatment. Secondary end points were sustained response rate at 12 months and cosmetic outcome at 3 and 12 months. Cosmesis and lesion recurrence were further assessed at 24 months.\n Data from 97 patients (105 lesions) were included in the 3-month per-protocol analysis. Complete response rates did not differ significantly between groups (51/52 [98%] lesions with surgery vs 48/53 [91%] lesions with methyl aminolevulinate PDT; difference [95% confidence interval], 4.8% (-3.4% to 13.0%]; P =.25). At 12 months, tumor-free rates were 50 (96%) of 52 lesions with surgery vs 44 (83%) of 53 with methyl aminolevulinate PDT (P =.15). More patients treated with methyl aminolevulinate PDT than surgery had an excellent or good cosmetic outcome at all time points (significant at 12 and 24 months on patient assessment, P<.05, and at 3, 12, and 24 months on investigator evaluation, P<.001). At 24 months, 5 lesions that had initially cleared with methyl aminolevulinate PDT had recurred, compared with 1 after surgery.\n Methyl aminolevulinate PDT is an effective treatment for nodular BCC, and while there is a trend for higher recurrence with this modality, it conveys the advantage over surgery of better cosmesis.",
"Current treatments for cutaneous leishmaniasis are limited by their toxicity, high cost, and discomfort and the emergence of drug resistance. New approaches, including combination therapies, are urgently needed. We performed a double-blind, randomized trial of therapy with parenteral antimony plus topical imiquimod, an innate immune-response modulator, versus therapy with antimony alone, in subjects with cutaneous leishmaniasis for whom an initial course of antimony therapy had failed.\n Forty subjects with clinical resistance to antimony were recruited in Lima, Peru, between February 2001 and December 2002. All subjects received meglumine antimoniate (20 mg/kg/day im or iv) and were randomized to receive either topical imiquimod 5% cream (Aldara; 3M Pharmaceuticals) or vehicle control every other day for 20 days. Lesions and adverse events were evaluated during treatment and at 1, 2, 3, 6, and 12 months after the treatment period.\n The mean number of lesions was 1.2 per person; 71% of the lesions were facial and 76% were ulcerative. There were no major differences between the groups, and all but 2 subjects completed therapy. Mild adverse events were reported by 73% of the subjects, but only erythema occurred more commonly in the imiquimod group (P < or = .02). Lesions resolved more rapidly in the imiquimod group: 50% of the imiquimod group achieved cure at 1 month after the treatment period versus 15% of the vehicle cream group (P < or = .02); 61% of the imiquimod group at 2 months versus 25% of the vehicle cream group (P < or = .03); and 72% of the imiquimod group at 3 months versus 35% of the vehicle cream group (P < or = .02). Residual scarring in the imiquimod group was less prominent than in the vehicle cream group.\n Combined antimony plus imiquimod treatment was well tolerated, accelerated healing of lesions, and improved scar quality. This therapy may have particular advantages for subjects with facial lesions.",
"To compare the efficacy, tolerance and safety of two types of cryotherapy, performed by family physicians, for benign cutaneous lesions: low freezing (-59 degrees C) with dimethyl either-propane cryogenic spray (DMEP) and intense freezing (196 degrees C) with conventional liquid nitrogen (LN).\n A randomised, multi-centered, controlled clinical trial, with single-blind assessment.\n Three primary care teaching teams in the Community of Madrid.\n Ten MIR from family & community medicine intervened. There were 124 patients, who had 174 benign cutaneous lesions, suitable for cryotherapy. There were 3 voluntary withdrawals, none because of an adverse reaction. Interventions, in each case there was local application for a standard time of the randomised agent. Control-group intervention, 81 cases: swab soaked in LN. Study-group intervention, 93 cases: swab saturated with DMEP spray. Maximum of three freezings per case, at weekly intervals.\n A doctor made a blind assessment of the results (elimination, adverse reaction, aesthetic result) 15 days after treatment.\n No clinically relevant differences between the efficacy, tolerance and safety of the two cryogenic agents used in primary care were found. The low freezing of DMEP was sufficient for the cryotherapy of benign lesions.",
"A randomized double-blind controlled trial of 130 patients was performed to study the efficacy and tolerability of topical 3% diclofenac in 2.5% hyaluronic acid (HA) gel (active) versus gel containing 2.5% HA alone (control) in the treatment of solar keratoses. Patients were asked to apply trial gel to the target lesion twice a day and also sunscreen once a day for 24 weeks. The complete response rates were 29% for the active gel and 17% for the control gel. The difference was not statistically significant (P = 0.14). A high percentage of patients in both groups experienced a partial response to treatment (38% active, 45% control) but there was no significant difference in the spectrum of response between the two treatments (P = 0.18). Local adverse reactions occurred significantly more frequently in patients using the active gel (29% compared to 5% using control gel, P = 0.0002).",
"Actinic keratosis (AK) is the earliest clinical manifestation of squamous cell carcinoma. Metastatic SCC causes the majority of the 1300 to 2300 deaths attributed to nonmelanoma skin cancer in the United States each year. Recent studies have shown that intralesional administration of interferon can be used successfully in the treatment of AK.\n Imiquimod is an immune response modifier, currently approved for the treatment of genital warts. The topically applied immune response modifier acts by up-regulating interferon and other cytokines involved in the cell-mediated immune response at the site of application. The aim of this was to determine the efficacy and safety of imiquimod 5% cream for the treatment of AK.\n Twenty-two patients with AK lesions were treated with imiquimod 5% cream, initially at 3 times per week for 8 weeks, or until total clearance of lesions. Patients applied imiquimod to lesions on one side of the body and vehicle cream to the other side. A total of 17 patients who completed treatment were evaluated for number of lesions and adverse reactions before treatment and at weeks 2, 4, 6, and 8 after initiation of treatment. AK lesions were also assessed 4 and 8 weeks after treatment.\n A significant reduction in the average number of lesions per patient was observed for patients treated with imiquimod. The most frequent reactions to treatment were erythema, itching, and scabbing; however, all adverse events were mild to moderate.\n Imiquimod 5% cream may be a promising treatment for AK.",
"This randomized, double-blind, placebo-controlled study assessed the efficacy and safety of a topical gel containing 3% diclofenac in 2.5% hyaluronan in 150 patients with solar keratoses (SK). The active treatment was compared with the vehicle only, hyaluronan gel, as placebo over a 12-week period. Patients in both groups applied the active treatment or placebo to a targeted area of skin (0.25 g b.d.). At 12 weeks the mean lesion-count reduction in the targeted area was not significantly different between treatments. However, at post-termination follow up (16 weeks), there was a highly significant decrease in the number of lesions, 6.2 +/- 7.5 standard deviations (SD) (56.1% reduction) in the active treatment group compared with 2.4 +/- 4.3 SD (23.6% reduction) in the placebo group (P < 0.001). Other efficacy measures (complete lesion resolution, >50% lesion reduction) were also significantly different (P < 0.01) between treatments at 16 weeks. In conclusion, topical 3% diclofenac in 2.5% hyaluronan gel was effective and well tolerated in this study, suggesting a role for this therapy in the treatment of SK.",
"Actinic keratoses (AK) are squamous cell carcinomas in situ and require treatment. Betulin-based oleogel prepared from a standardized triterpene dry extract from birch bark represents a new topical agent with anti-inflammatory and anti-tumor potential.\n In the prospective, randomized, monocentric phase 2a study 45 patients with < 10 AK were included and randomly assigned to one of the three treatment groups. Intervention consisted of topical betulin-based oleogel twice daily versus cryotherapy with liquid nitrogen versus the combination of cryotherapy with topical betulin-based oleogel. Treatment response was assessed clinically after three months. The clinical response was graded into complete clearing (100 %), therapy responders (> 75 % clearing of the lesions) and non-responders (< 75 % clearing). Additionally, punch biopsies were obtained from some patients before and at the end of treatment.\n Therapy with betulin-based oleogel was well tolerated.Three patients discontinued therapy because of personal reasons. After three months, the 100% (and > 75%) clearing rates of the lesions were as follows: 64% (86%) with betulin-based oleogel (n = 14),79% (93%) with cryotherapy (n = 14),and 71% (71%) with the combined therapy (n = 14). Histological analysis of biopsies taken before and after treatment (n = 8) showed a reduced degree of dysplasia in the epidermis in all study arms.\n Betulin-based oleogel seems to be an effective novel approach in the topical treatment of actinic keratoses. However,the clinical and histological findings of the present pilot study have to be verified against placebo with larger case numbers.",
"Efficient treatment of patients with multiple synchronous nonmelanoma skin cancers represents a therapeutic challenge.\n To study the safety and efficacy of photodynamic therapy (PDT) with verteporfin and red light in the treatment of multiple nonmelanoma skin cancers.\n Open-label, randomized, multicenter, dose-ranging phase 2 study conducted at 4 North American university-based dermatology clinics.\n Fifty-four patients with 421 multiple nonmelanoma skin cancers including superficial and nodular basal cell carcinoma and squamous cell carcinoma in situ (Bowen disease).\n A single intravenous infusion of 14 mg/m(2) of verteporfin followed 1 to 3 hours later by exposure of tumors to 60, 120, or 180 J/cm(2) of red light (688 +/- 10 nm) from a light-emitting diode panel.\n Pathologic response of treated sites was assessed at 6 months. Clinical and cosmetic responses were assessed and graded at 6 weeks, 3 months, and 6 months after verteporfin PDT, with optional follow-up visits at 12, 18, and 24 months.\n The histopathologic response, defined as absence of tumor on biopsy specimens 6 months after verteporfin PDT, ranged from 69% at 60 J/cm(2) to 93% at 180 J/cm(2). At 24 months of follow-up (276 tumors in 31 patients), the clinical complete response rate ranged from 51% at 60 J/cm(2) to 95% at 180 J/cm(2). No significant systemic adverse events were observed; most events occurred at the treated tumor sites and included events such as pain. Overall, 65% (95% confidence interval, 58%-71%) of tumors were judged to have good to excellent cosmesis at 24 months.\n A single course of verteporfin PDT showed treatment benefit for patients with multiple nonmelanoma skin cancers.",
"Organ transplant recipients (OTR) are at high risk of developing nonmelanoma skin cancer and premalignant epidermal dysplasia (carcinoma in situ/ Bowen's disease and actinic keratoses). Epidermal dysplasia is often widespread and there are few comparative studies of available treatments.\n To compare topical methylaminolaevulinate (MAL) photodynamic therapy (PDT) with topical 5% fluorouracil (5-FU) cream in the treatment of post-transplant epidermal dysplasia.\n Eight OTRs with epidermal dysplasia were recruited to an open-label, single-centre, randomized, intrapatient comparative study. Treatment with two cycles of topical MAL PDT 1 week apart was randomly assigned to one area of epidermal dysplasia, and 5-FU cream was applied twice daily for 3 weeks to a clinically and histologically comparable area. Patients were reviewed at 1, 3 and 6 months after treatment. The main outcome measures were complete resolution rate (CRR), overall reduction in lesional area, treatment-associated pain and erythema, cosmetic outcome and global patient preference.\n At all time points evaluated after completion of treatment, PDT was more effective than 5-FU in achieving complete resolution: eight of nine lesional areas cleared with PDT (CRR 89%, 95% CI: 0.52-0.99), compared with one of nine lesional areas treated with 5-FU (CRR 11%, 95% CI: 0.003-0.48) (P = 0.02). The mean lesional area reduction was also proportionately greater with PDT than with 5-FU (100% vs. 79% respectively). Cosmetic outcome and patient preference were also superior in the PDT-treated group.\n Compared with topical 5-FU, MAL PDT was a more effective and cosmetically acceptable treatment for epidermal dysplasia in OTRs and was preferred by patients. Further studies are now required to confirm these results and to examine the effect of treating epidermal dysplasia with PDT on subsequent development of squamous cell carcinoma in this high risk population.",
"Cutaneous leishmaniasis (CL) is a serious public health problem in many tropical and subtropical regions of the world. Treatment of CL can prevent disfiguring scars.\n The efficacy of local heat therapy by radiofrequency (RF) was compared with intralesional injection of meglumine antimoniate in the treatment of CL.\n This was a randomized clinical trial. Patients with antroponotic cutaneous leishmaniasis (ACL) in the Isfahan province of Iran were enrolled in the study if the examination of a smear from a suspected CL lesion was confirmed positive for Leishmania. Patients were randomly allocated to one of two treatment groups. Group A was treated by heat therapy by RF at 50 degrees C for 30 s once weekly for 4 weeks, and group B was treated with intralesional injection of meglumine antimoniate once weekly for 4 weeks. Follow-up lasted 6 months. Response to treatment was classified as complete (lesions flattened, no induration, and epidermal creases had appeared), partial (reduction in lesion size, but without the appearance of epidermal creases) and poor (no reduction in lesion size).\n Of 117 participants, 57 patients with 83 lesions in group A and 60 patients with 94 lesions in group B completed the study and were followed up for 6 months. Complete, partial and poor response to treatment were 80.7%, 12% and 7.3% in group A, and 55.3%, 21.27% and 23.40% in group B, respectively (P = 0.001). In both groups, there was no relapse in patients with complete response after 6 months of follow-up.\n Heat therapy with thermogenerator RF can be used as an efficacious treatment in the lesions of CL. It is more effective than the conventional treatment with intralesional meglumine antimoniate injection.",
"The purpose of this pilot study was to determine if photodynamic therapy with topical application of 5-aminolaevulinic acid followed by irradiation with incoherent filtered and unfiltered light (ALA-PDT) is an effective therapy for recalcitrant hand and foot warts. In 30 patients with recalcitrant warts, 49 regions with a total of 250 warts were randomized to one of the following five treatments: (i) ALA-PDT with white light applied three times within 10 days (W3); (ii) ALA-PDT with white light applied once (W1); (iii) ALA-PDT with red light applied three times within 10 days (R3); (iv) ALA-PDT with blue light applied three times within 10 days (B3), and (v) cryotherapy applied up to four times within 2 months (CRYO). The ALA-PDT treatment modality was repeated in case of partially responding warts. Significantly more warts were completely healed after W3 and W1 than after R3, B3 and CRYO (P < 0.01): 73% of the warts treated with W3 were completely healed, 71% after W1, 42% after R3, 23% after B3 and 20% after CRYO. No scars were observed in the ALA-PDT treated areas and patients treated for foot warts were all able to walk after the treatment. No recurrences in completely responding ALA-PDT treated warts were observed after 12 months of follow-up. In conclusion, photodynamic therapy with topical 5-aminolaevulinic acid followed by irradiation with white light is a promising treatment for recalcitrant hand and foot warts.",
"Narrowband ultraviolet B (NB-UVB) phototherapy, with a 308-nm xenon chloride excimer laser, and targeted UVB phototherapy have produced encouraging therapeutic results for vitiligo. However, very few studies employing broadband UVB exist. Moreover, there has been no direct comparison study between broadband UVB and NB-UVB for the treatment of vitiligo. The aims of this study were to compare the repigmenting efficacy of targeted broadband UVB phototherapy with that of NB-UVB in an equi-erythemogenic manner. Twenty identical vitiliginous lesions from 10 patients were randomly allocated to receive either targeted broadband UVB or targeted NB-UVB phototherapy. UV fluences were started at 50% of the minimal erythema dose detected within the vitiliginous patches, then increased gradually, in the same manner, to ensure equi-erythemogenic comparison. Treatments were carried out twice weekly for 12 weeks. The results show that grade 1, i.e. 1-25% repigmentation, to grade 2, 26-50% repigmentation, occurred in 6 of 10 subjects. Responses in terms of repigmentation, de-pigmentation, or lack thereof, were similar between lesions receiving broadband and NB-UVB phototherapy. Onset of repigmentation occurred as early as 4 weeks of treatment in most subjects. Treatments were well tolerated, with only minimal erythema and hyperpigmentation.\n The study was carried out in a small number of patients with skin types III, IV and V. The irradiation device was a targeted UVB device and thus the results may not be applicable to other light sources, such as the excimer laser or total-body irradiation cabinets. In conclusion, targeted broadband UVB produces similar clinical responses to targeted NB-UVB in the treatment of the non-segmental type of vitiligo.",
"The optimal treatment for cutaneous leishmaniasis (CL) is not known. Topical paromomycin is one of the many drugs that have been suggested for the treatment of CL caused by Leishmania major. Recently, topical photodynamic therapy (PDT) has been reported to be effective in the treatment of CL.\n To compare the parasitological and clinical efficacy of PDT vs. topical paromomycin in patients with Old World CL caused by L. major in Iran.\n In this trial, 60 patients with the clinical and parasitological diagnosis of CL were recruited and were randomly divided into three treatment groups of 20 subjects each. Group 1 was treated with weekly topical PDT, and groups 2 and 3 received twice-daily topical paromomycin and placebo, respectively. The duration of treatment was 4 weeks for all groups. These groups were followed for 2 months after the end of treatment.\n In total, 57 patients with 95 lesions completed the study. At the end of the study, complete improvement was seen in 29 of 31 (93.5%), 14 of 34 (41.2%) and 4 of 30 lesions (13.3%) in groups 1, 2 and 3, respectively (P<0.001). At the same time point, 100%, 64.7% and 20% of the lesions had parasitological cure in group 1, 2 and 3, respectively (P<0.001).\n Topical PDT can be used safely as a rapid and highly effective alternative treatment choice for Old World CL in selected patients.",
"Hypericin is a known photodynamic agent that has been demonstrated to induce apoptosis in normal and malignant B and T lymphocytes, and has potential to treat benign and malignant disorders of the skin, including psoriasis and cutaneous T-cell lymphoma.\n We wished to test whether topical hypericin was an effective, safe, and well-tolerated therapy for patch or plaque phase mycosis fungoides and for plaque psoriasis.\n We conducted a phase II placebo-controlled clinical study in patients who had either patch or plaque phase mycosis fungoides or plaque type psoriasis vulgaris. Representative lesions were treated twice weekly for 6 weeks with topically applied hypericin or placebo followed 24 hours later by exposure to visible light at 8 to 20 J/cm(2).\n After 6 weeks of twice-weekly therapy, several concentrations of hypericin resulted in the significant improvement of treated skin lesions among the majority of patients with cutaneous T-cell lymphoma and psoriasis whereas the placebo vehicle was ineffective.\n The clinical trial involved a small number of patients.\n Overall, the data from this study support the conclusion that topical hypericin/visible light photodynamic therapy is an effective and well-tolerated alternative to standard psoralen plus ultraviolet A treatment of these disorders.\n Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.",
"Imiquimod has been investigated as a safe and effective therapeutic option for the treatment of actinic keratosis (AK).\n To evaluate imiquimod vs. vehicle applied three times a week for 4 weeks in one or two courses of treatment for AK on the face or balding scalp.\n Patients diagnosed with AK were enrolled in this multicentre, vehicle-controlled, double-blind study conducted in Europe. Twenty study centres enrolled a total of 259 patients in this study. Patients applied the study drug for 4 weeks, entered a 4-week rest period and if they did not have complete clearance, they then entered a second course of treatment.\n Patients in the imiquimod group had an overall complete clearance rate of 55.0% (71/129) vs. a rate of 2.3% (3/130) for the vehicle group. There was a high rate of agreement between the clinical assessment and histological findings with respect to AK lesion clearance. At both 8-week post-treatment visits, the negative predictive value of the investigator assessment was 92.2% for clinical assessments vs. histological results.\n A 4-week course of treatment with three times weekly dosing of imiquimod 5% cream, with a repeated course of treatment for those patients who fail to clear after the first course of treatment, is a safe and effective treatment for AK. The overall complete clearance rate (complete clearance after either course 1 or course 2) is comparable to the 16-week treatment regimen, while decreasing drug exposure to the patient and decreasing the overall treatment time.",
"The immune system plays a critical role in the development and pathogenesis of actinic keratosis (AK). Imiquimod has been shown to stimulate the cutaneous immune response and be effective for the treatment of nonmelanoma skin cancers.\n Two phase III, randomized, double-blind, vehicle-controlled studies evaluated the efficacy of imiquimod 5% cream compared with vehicle in the treatment of AK lesions on the face and balding scalp.\n A total of 436 participants at 24 centers in the United States and Canada were randomized to either imiquimod 5% or vehicle cream. Study cream was applied one time per day, 2 days per week for 16 weeks. Clearance of AK lesions was clinically assessed at an 8-week posttreatment visit.\n The complete clearance rate was 45.1% for the imiquimod group and 3.2% for the vehicle group. The difference in complete clearance rates (imiquimod minus vehicle) was 41.9% with a 95% confidence interval of 34.9% to 49%. The partial (> or =75%) clearance rate was 59.1% for the imiquimod group and 11.8% for the vehicle group. The difference in partial clearance rates (imiquimod minus vehicle) was 47.3% with a 95% confidence interval of 39.5% to 55.1%. The median percent reduction in AK lesions was 83.3% for the imiquimod group and 0% for the vehicle group. Local skin reactions were common. Severe erythema was reported by 17.7% of participants who received imiquimod and 2.3% of participants who received vehicle. Overall, imiquimod was very well tolerated.\n Imiquimod 5% cream used 2 times per week for 16 weeks is an effective and well-tolerated treatment for AK.",
"Recently, a randomised study demonstrated the utility of oral cooling (cryotherapy) in the prevention of 5-fluorouracil (5FU)-induced stomatitis. In order to verify these results a confirmatory study, using identical treatment regimen, was initiated. 84 patients treated with a 5-FU-containing regimen were randomised to a control arm or to receive oral cryotherapy. End point evaluation was obtained by a global assessment of the physician's judgement and patients' description of mucositis severity graded 0-4. Mucositis was significantly reduced by cryotherapy considering both the first cycle of therapy (the mean toxicity score for cryotherapy was 0.59 and it was 1.1 for the control group, P < or = 0.05) and all the chemotherapeutic courses (the mean toxicity score for cryotherapy was 0.36 when it was 0.69 for the control group, P < or = 0.05). In conclusion, the present study confirms that cryotherapy can decrease 5FU-induced stomatitis and should be recommended for patients receiving bolus 5FU-containing regimens.",
"Resiquimod, a toll-like receptor 7 and 8 agonist, may be effective as a topical treatment of actinic keratosis (AK).\n To evaluate the effect of resiquimod gel concentration on lesion clearance.\n Patients with AK lesions on the face or balding scalp were randomly assigned to resiquimod 0.01%, 0.03%, 0.06% or 0.1% gel applied once daily three times a week for 4 weeks to a contiguous 25-cm(2) area with four to eight lesions. Patients with persistent lesions received a second course after an 8-week treatment-free interval. Complete and partial lesion clearance was assessed 8 weeks after treatment for each course.\n For the 132 patients randomized, overall complete clearance rates were 77.1% (27/35), 90.3% (28/31), 78.1% (25/32) and 85.3% (29/34) and complete clearance rates after course 1 only were 40.0%, 74.2%, 56.3% and 70.6%, respectively, for the resiquimod 0.01%, 0.03%, 0.06% and 0.1% groups. During course 1, respectively 0%, 13%, 31% and 38% of patients discontinued treatment for adverse events or local skin reactions, for the resiquimod 0.01%, 0.03%, 0.06% and 0.1% groups. Possibly or probably related nonapplication site adverse events of severe intensity, including influenza-like symptoms, were reported by 0%, 3%, 13% and 12% of patients, respectively, for the resiquimod 0.01%, 0.03%, 0.06% and 0.1% groups.\n Efficacy in clearing AK lesions was similar between the resiquimod concentrations evaluated, but resiquimod 0.01% and 0.03% were better tolerated than the higher concentrations.",
"Actinic keratoses (AKs) are precancerous epidermal lesions found most frequently on areas of the skin exposed to the sun. Several case studies published recently have indicated that 5% imiquimod cream, currently licensed for the treatment of genital warts, may be an effective treatment for AK.\n To assess the efficacy and safety of imiquimod for the treatment of AK.\n Patients in this randomized, double-blind, vehicle-controlled study applied 5% imiquimod cream or vehicle to AK lesions 3 times per week for a maximum of 12 weeks or until lesions had resolved. In the event of an adverse reaction, application of imiquimod was reduced to 1 or 2 times per week. Rest periods were also allowed if necessary.\n A specialized outpatient dermatology clinic within a state-funded hospital in Germany.\n The study population was aged 45 to 85 years. Of 52 patients screened, 36 men and women with AK confirmed by histological diagnosis were enrolled. Patients were excluded from the study if they did not have a histological diagnosis for AK, if they were older than 85 years, or if they did not comply with the protocol. All patients had responded to a notice asking for volunteers.\n The number and appearance of lesions were evaluated before, during, and after treatment. All adverse effects were recorded.\n Lesions treated with 5% imiquimod cream were clinically cleared in 21 (84%) of 25 patients and partially cleared in 2 (8%). Clearance was histologically confirmed 2 weeks after the last application of imiquimod in all patients clinically diagnosed as lesion free. Only 10% of patients treated with imiquimod were clinically diagnosed with recurrence 1 year after treatment. No reduction in the size or number of AK lesions was observed in vehicle-treated patients. Adverse effects reported by patients treated with imiquimod included erythema, edema, induration, vesicles, erosion, ulceration, excoriation, and scabbing. However, imiquimod was well tolerated since all patients completed the 12-week treatment. Only a few, mild adverse reactions to the vehicle cream were reported.\n Application of 5% imiquimod cream for 12 weeks is an effective and well-tolerated treatment for AK.",
"Vitiligo is a common, idiopathic, acquired, depigmenting disease characterized by loss of normal melanin pigments in the skin. The most interesting treatment methods for extensive vitiligo involve psoralen plus ultraviolet A (PUVA) therapy and ultraviolet (UV)-B phototherapy, particularly narrow-band UV-B. In this randomized and comparative study, we investigated the safety and efficacy of narrow band ultraviolet B as monotherapy and in combination with topical calcipotriol in the treatment of generalized vitiligo. Of the 40 vitiligo patients enrolled in the study, 15 were treated with the calcipotriol plus narrow-band UV-B (NBUVB) and 25 with narrow band UV-B alone. The patients were randomized into two NBUVB treatment groups. The first group, consisting of 24 patients (all male), received only NBUVB treatment; the second group, consisting of 13 patients (all male) applied 0.05% topical calcipotriol ointments twice daily. Both groups were irradiated with NBUVB (311 nm). In the NBUVB group, the percentage of the body surface affected was reduced from 27.21 +/- 10.41% to 16.25 +/- 8.54% after a mean of 30 treatment sessions. The mean repigmentation percentage was 41.6 +/- 19.4%. In clinical evaluation (moderate and marked/complete response was accepted as an effective treatment), 19 patients (19/24; 79.17%) had clinically good results. In the NBUVB plus calcipotriol group, the percentage of the body surface affected was reduced from 23.35 +/- 6.5% to 13.23 +/- 7.05% after a mean of 30 treatment sessions. The mean repigmentation percentage was 45.01 +/- 19.15%. In clinical evaluation (moderate and marked/complete response was accepted as an effective treatment), 10 patients (10/13; 76.92%) had clinically good results. Statistically significant intragroup reductions from the baseline percentage of the body surface affected were seen at the endpoint of treatment for the two treatment groups (P < 0.001). However, there was no statistically significant difference between the two treatment groups at the end of therapy with respect to the reduction of repigmentation rates (P > 0.05). The present study reconfirmed the efficacy of NBUVB phototherapy in vitiligo. It can be a therapeutic option considered in the management of patients with vitiligo. However, addition of topical calcipotriol to NBUVB did not show any advantage.",
"The authors previously reported that 30 minutes of oral cryotherapy inhibits 5-fluorouracil (5-FU)-induced stomatitis. The current trial was designed to determine whether a longer duration of cryotherapy would provide additional protection.\n This trial involved patients who were receiving their first course of a 5-FU plus leucovorin chemotherapy regimen, for which stomatitis is a major dose-limiting toxicity. These patients were randomized to receive either 30 or 60 minutes of oral cryotherapy given at around the same time as the 5-FU therapy.\n A total of 178 evaluable patients were studied. Both cryotherapy groups had similar degrees of mucositis.\n The authors continue to recommend the use of 30 minutes of oral cryotherapy for patients receiving bolus intensive courses of 5-FU-based chemotherapy.",
"In the conservative therapy of venous leg ulcers modern types of dressings are used most frequently. In the past 20 years 'active wound dressings' - cultured epidermal keratinocytes as autografts and allografts - were also introduced in the management of leg ulcers.\n The aim of our study was to compare the effect of cryopreserved and lyophilized cultured epidermal allografts in the treatment of venous leg ulcers. Evaluation of the therapy was documented as photodocumentation, planimetry, healing time and evaluation of pain relief over a 3-month period after application. Fifty patients with venous leg ulcers were selected. Twenty-five patients (group I) were treated with cryopreserved keratinocytes and 25 (group II) with lyophilized keratinocytes.\n The final evaluation 3 months after the application of allografts showed 84% of healed ulcers in group I and 80% in group II. The number of healed ulcers and the healing rate both showed no statistically significant differences. The size of the ulcer was reduced by half during the first week in both groups. The size differences during the first week are statistically significant in both groups and they are comparable (P < 0.001). The intensity of the pain was statistically significantly reduced during the first week after application in both groups (P < 0.001).\n The cryopreserved and lyophilized cultured allografts are comparable in healing rate, course of healing and relief of pain, and also in planimetric changes during the healing of venous leg ulcers. Lyophilized allografts are more convenient for routine use than cryopreserved allografts as they can be stored at room temperature. These results could give rise to the more frequent use of lyophilized allografts in slow-healing venous leg ulcers.",
"A dual-centre, randomized, double-blind, vehicle-controlled study was conducted to evaluate the safety and efficacy of short courses of therapy with imiquimod 5% cream in clearing >/=75% of baseline solar keratoses (SK) within a field of treatment. Subjects with 5-15 baseline SK within one treatment area (scalp, forehead and temples, or both cheeks) were randomized to apply imiquimod or vehicle cream to the entire treatment area three times a week for 3 weeks. Subjects were assessed 4 weeks after completing the first course for clearance of lesions. Subjects with <75% clearance were commenced on a second 3-week course of study cream. Subjects with >/=75% clearance were followed up until study completion without further therapy. All subjects were evaluated at the study endpoint of 14 weeks after initiating therapy for assessment of the primary outcome (>/=75% clearance of baseline solar keratoses). Twenty-one out of 29 (72%) imiquimod-treated subjects cleared >/=75% of baseline lesions compared with 3/10 (30%) subjects using the vehicle cream (Fisher's exact test, P = 0.027). Imiquimod was well tolerated. The present study has a short follow-up endpoint, but suggests that imiquimod is a potential therapeutic alternative in patients with SK.",
"Common warts (verrucae vulgares) are human papilloma virus (HPV) infections with a high incidence and prevalence, most often affecting hands and feet, being able to impair quality of life. About 30 different therapeutic regimens described in literature reveal a lack of a single striking strategy. Recent publications showed positive results of photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) in the treatment of HPV-induced skin diseases, especially warts, using visible light (VIS) to stimulate an absorption band of endogenously formed protoporphyrin IX. Additional experiences adding waterfiltered infrared A (wIRA) during 5-ALA-PDT revealed positive effects.\n First prospective randomised controlled blind study including PDT and wIRA in the treatment of recalcitrant common hand and foot warts. Comparison of \"5-ALA cream (ALA) vs. placebo cream (PLC)\" and \"irradiation with visible light and wIRA (VIS+wIRA) vs. irradiation with visible light alone (VIS)\".\n Pre-treatment with keratolysis (salicylic acid) and curettage. PDT treatment: topical application of 5-ALA (Medac) in \"unguentum emulsificans aquosum\" vs. placebo; irradiation: combination of VIS and a large amount of wIRA (Hydrosun) radiator type 501, 4 mm water cuvette, waterfiltered spectrum 590-1400 nm, contact-free, typically painless) vs. VIS alone. Post-treatment with retinoic acid ointment. One to three therapy cycles every 3 weeks. Main variable of interest: \"Percent change of total wart area of each patient over the time\" (18 weeks). Global judgement by patient and by physician and subjective rating of feeling/pain (visual analogue scales). 80 patients with therapy-resistant common hand and foot warts were assigned randomly into one of the four therapy groups with comparable numbers of warts at comparable sites in all groups.\n The individual total wart area decreased during 18 weeks in group 1 (ALA+VIS+wIRA) and in group 2 (PLC+VIS+wIRA) significantly more than in both groups without wIRA (group 3 (ALA+VIS) and 4 (PLC+VIS)): medians and interquartile ranges: -94% (-100%/-84%) vs. -99% (-100%/-71%) vs. -47% (-75%/0%) vs. -73% (-92%/-27%). After 18 weeks the two groups with wIRA differed remarkably from the two groups without wIRA: 42% vs. 7% completely cured patients; 72% vs. 34% vanished warts. Global judgement by patient and by physician and subjective rating of feeling was much better in the two groups with wIRA than in the two groups without wIRA.\n The above described complete treatment scheme of hand and foot warts (keratolysis, curettage, PDT treatment, irradiation with VIS+wIRA, retinoic acid ointment; three therapy cycles every 3 weeks) proved to be effective. Within this treatment scheme wIRA as non-invasive and painless treatment modality revealed to be an important, effective factor, while photodynamic therapy with 5-ALA in the described form did not contribute recognisably - neither alone (without wIRA) nor in combination with wIRA - to a clinical improvement. For future treatment of warts an even improved scheme is proposed: one treatment cycle (keratolysis, curettage, wIRA, without PDT) once a week for six to nine weeks.",
"New therapeutic options would benefit patients with actinic keratosis (AK), a precancerous condition that is a significant health concern. The efficacy and safety of a microsphere-based formulation of 0.5% fluorouracil cream were evaluated in a randomized, double-blind, multicenter, parallel-group study. Patients (N= 177) were randomized to receive 0.5% fluorouracil or vehicle once daily for 1, 2, or 4 weeks. Efficacy was assessed by lesion counts and clearance. Safety was evaluated by monitoring adverse events, including facial irritation. Significant improvements were seen from baseline to posttreatment follow-up in all efficacy variables for all fluorouracil regimens compared with vehicle. Patients treated for one week experienced significant improvements compared with vehicle, although efficacy increased with increasing treatment duration. Most patients experienced mild to moderate facial irritation of predictable onset and duration. Once-daily administration of 0.5% fluorouracil cream for 1, 2, or 4 weeks is safe and effective for the treatment of AKs.",
"Increasing incidence rates of cutaneous malignancies, paralleling rising survival times of grafts and patients in organ transplant recipients, represents an escalating challenge for dermatologists worldwide. Especially, invasive squamous cell carcinomas (SCC) in immuno-compromised patients are characterized by significantly increased morbidity and mortality and characteristically outnumber basal cell carcinoma in this population. Effective management of actinic keratoses (AK) could help to prevent the further development of invasive SCC. Diclofenac in hyaluronic acid has previously shown to be an effective and well tolerated option for the treatment of AK in immuno-competent patients. However, its safety and efficacy in organ-transplant patients has not been evaluated in a controlled study so far. 32 organ transplant patients (kidney (+/- pancreas), liver, heart) screened at our specialized transplant dermatology outpatient clinic were found eligible and were randomized to either active treatment (24) or vehicle (8). Patients who had stable status of the transplanted graft in the 12 months prior to entering the study and >/= 3 AK lesions in a contiguous 50 cm2 area on the face, forehead, hands or balding scalp were eligible for inclusion in the study. Treatment of AK with 3% diclofenac in 2.5% hyaluronic acid or placebo twice daily was conducted over a total of 16 weeks, followed by a final evaluation 4 weeks after last application of the study drug. Biopsies were taken from the treated areas at the final visit to verify clinical clearance. Patients were assessed for safety variables that included adverse events, local skin reactions, laboratory results, dosage of immunosuppressive medication and indication of graft rejection. A 24 months follow up was conducted after the end of treatment. 87% (n = 28/32) of the patients completed the 16 week treatment phase and presented for final evaluation 4 weeks after end of treatment. In the diclofenac 3% gel treatment group, a complete clearance of AK lesions was achieved in 41% (9/22) compared to 0% (0/6) in the vehicle group. Side effects in most of the patients included a mild erythema and a mild to moderate swelling of the areas treated. No graft rejections or trends for a deterioration of graft function were detected. No meaningful trends were observed in laboratory results. In 55% of the previously cleared patients, new AK developed in the study area after an average of 9.3 months. None of these patients developed invasive SCC in the study area within 24 months of follow-up. This study demonstrated a greater lesion clearance rate of AKs in OTRs treated with diclofenac 3% gel than with vehicle. Despite recurrent AK in 55% of the previously cleared patients, the 24 month results showed no invasive SCC in this group. This study suggests that diclofenac 3% gel is not only an efficient and well tolerated treatment for multiple AKs in OTRs but also may prevent invasive SCC in these high-risk patients.",
"The role of topical 5-fluorouracil (5-FU) in treating common warts is not well defined. We tried to evaluate the efficacy and adverse effects of combination cryotherapy and topical 5% 5-FU ointment in the treatment of common warts. The study was a single-centre, double-blind randomized placebo-controlled trial. In the study, 80 patients with common warts were randomized into two groups and underwent two 10-second freeze/thaw cycles of cryotherapy with liquid nitrogen once every three weeks for a maximum of five treatments. Between treatments, patients applied either topical 5% 5-FU ointment (group A) or placebo aqueous cream (group B) twice daily. The mean +/- SD reduction in wart area was 58.57 +/- 0.06% in group A and 65.29 +/- 0.06% in group B. In total, 19 patients in group A and 24 patients in group B had wart size reduced by 75% or more (P = 0.50), while 12 patients in group A and 17 patients in group B had clearance of their warts (P = 0.245). Logistic regression with age, sex, smoking status, immune status, site, duration and number of warty lesions, history of previous treatment, and treatment group found that only a history of previous treatment and acral lesions were significant adverse predictors of improvement. There was no significant difference in the number of adverse events between the two groups, although there was a trend towards more pain and blistering associated with topical 5-FU. We concluded that topical 5-FU has no added benefit in treating common warts with cryotherapy."
] |
For individual lesions, photodynamic therapy appears more effective and has a better cosmetic outcome than cryotherapy. For field-directed treatments, diclofenac, 5-fluorouracil, imiquimod, and ingenol mebutate had similar efficacy, but their associated adverse events and cosmetic outcomes are different. More direct comparisons between these treatments are needed to determine the best therapeutic approach.
|
CD003986
|
[
"10541229",
"3892073",
"8315258",
"9109861"
] |
[
"Failure of the competitive N-methyl-D-aspartate antagonist Selfotel (CGS 19755) in the treatment of severe head injury: results of two phase III clinical trials. The Selfotel Investigators.",
"Disease-specific amino acid infusion (F080) in hepatic encephalopathy: a prospective, randomized, double-blind, controlled trial.",
"Long-term treatment of latent portosystemic encephalopathy with branched-chain amino acids. A double-blind placebo-controlled crossover study.",
"Quantitative assessment of sustained-release 4-aminopyridine for symptomatic treatment of multiple sclerosis."
] |
[
"Excessive activity of excitatory amino acids released after head trauma has been demonstrated to contribute to progressive injury in animal models and human studies. Several pharmacological agents that act as antagonists to the glutamate receptor have shown promise in limiting this progression. The efficacy of the N-methyl-D-aspartate receptor antagonist Selfotel (CGS 19755) was evaluated in two parallel studies of severely head injured patients, defined as patients with post resuscitation Glasgow Coma Scale scores of 4 to 8.\n A total of 693 patients were prospectively enrolled in two multicenter double-blind studies. Comparison between the treatment groups showed no significant difference with regard to demographic data, previous incidence of hypotension, and severity of injury. As the study progressed, the Safety and Monitoring Committee became concerned about possible increased deaths and serious brain-related adverse events in the treatment arm of the two head injury trials, as well as deaths in the two stroke trials being monitored concurrently. The Selfotel trials were stopped prematurely because of this concern and because an interim efficacy analysis indicated that the likelihood of demonstrating success with the agent if the studies had been completed was almost nil.\n Subsequently, more complete data analysis revealed no statistically significant difference in mortality rates in all cases between the two treatment groups in the head injury trials. In this report the authors examine the studies in detail and discuss the potential application of the data to future trial designs.",
"Seventy-five patients with acute hepatic decompensation superimposed on chronic alcoholic cirrhosis were prospectively randomized for a blinded trial of the treatment of hepatic encephalopathy. The control group received 4 g of enteral neomycin daily along with 25% dextrose by a central venous catheter. The experimental group received a placebo resembling neomycin and isocaloric dextrose plus a modified amino acid mixture enriched with branched-chain amino acids to 36% and deficient in aromatic amino acids and methionine. Thirty patients in the F080 group and 29 in the control group completed the trial. The group receiving the modified amino acid mixture demonstrated a statistically significant improvement in encephalopathy as compared to the neomycin group, while maintaining nitrogen equilibrium. Survival and discharge from the hospital were statistically greater in the group treated with the modified amino acid solution and hypertonic dextrose. Treatment of hepatic encephalopathy in the presence of hepatic decompensation with an amino acid solution formulated for its treatment seems to produce faster, more complete recovery with improved capacity for nutritional support.",
"This trial was undertaken to assess the safety and efficacy of long-term oral supplementation with branched-chain amino acids as an adjunct to conventional therapy in patients with stable cirrhosis and latent encephalopathy. Latent encephalopathy was diagnosed by psychometric testing, used to assess automobile driving capacity. Seventeen patients with impaired driving capacity received either branched-chain amino acids or placebo for 8 weeks before being crossed over to the other regimen for an equal period. Branched-chain amino acids but not placebo significantly improved psychomotor disturbances (p < 0.01) and driving capacity (p < 0.002). No adverse reactions were observed. We conclude that long-term branched-chain amino acid supplementation is well tolerated and effective in the treatment of impaired automobile driving capacity associated with latent portosystemic encephalopathy.",
"To evaluate the efficacy of 4-aminopyridine sustained release (4AP SR) (fampridine, EL-970) using quantitative measures of motor function in multiple sclerosis (MS) patients.\n In vitro, 4AP improves conduction through demyelinated axons. A previous multicenter trial of 4AP SR using the Expanded Disability Status Scale (EDSS) as the primary outcome was unable to establish clinical efficacy.\n Ten MS patients with stable motor deficits (EDSS 6.0-7.5) were given 4AP SR 17.5 mg bid and placebo for 1 week each in a double-blind, placebo-controlled, crossover trial. Time to walk 8 meters, time to climb four stairs, maximum voluntary isometric contraction measured quantitatively (MVICT), manual muscle testing (MMT), grip strength, EDSS, and the patient's global impression were measured.\n Timed gait was improved on 4AP SR compared with placebo in 9 of 10 subjects (p = 0.02). Timed stair climbing, MVICT, MMT, grip strength, and EDSS showed nonsignificant improvements on 4AP SR. Based on their global impressions, seven subjects preferred 4AP SR over placebo; only one preferred placebo. There were no serious side effects.\n 4AP SR improved motor function in MS patients. The quantitative outcomes used in this study permit more sensitive evaluation of the therapeutic effect and promise to be useful in future trials of symptomatic treatments for MS."
] |
The case for efficacy of excitatory amino acid inhibitor therapy remains unproven. To date, no product has proven to be efficacious (as determined by the criteria applied) for improving the outcomes of brain-injured patients. Early termination, unpublished, and underpowered studies limit a clear appreciation of the merits of this form of intervention. Additional studies, some of which remain in progress, may more clearly define the efficacy and effectiveness issues.
|
CD003148
|
[
"12948999",
"15066200",
"8430715",
"18515890",
"19091806",
"16509174",
"18442509",
"11784832",
"17014748",
"16816304"
] |
[
"Efficacy of an evidence-based cognitive stimulation therapy programme for people with dementia: randomised controlled trial.",
"An outreach intervention to implement evidence based practice in residential care: a randomized controlled trial [ISRCTN67855475].",
"Immunologic and psychologic therapy for patients with chronic fatigue syndrome: a double-blind, placebo-controlled trial.",
"Cognitive--behavioural therapy and family intervention for relapse prevention and symptom reduction in psychosis: randomised controlled trial.",
"Conducting a randomized clinical trial of an psychological intervention for parents/caregivers of children with cancer shortly after diagnosis.",
"Benefits of an education programme on the self-management of aerosol and airway clearance treatments for children with cystic fibrosis.",
"A randomized controlled trial of a new behavioral home-based nutrition education program, \"Eat Well with CF,\" in adults with cystic fibrosis.",
"Evaluation of cognitive assessment and cognitive intervention for people with multiple sclerosis.",
"Cognitive behavioural therapy in chronic fatigue syndrome: a randomised controlled trial of an outpatient group programme.",
"Outcomes of an effectiveness trial of cognitive-behavioural intervention by mental health nurses in schizophrenia."
] |
[
"A recent Cochrane review of reality orientation therapy identified the need for large, well-designed, multi-centre trials.\n To test the hypothesis that cognitive stimulation therapy (CST) for older people with dementia would benefit cognition and quality of life.\n A single-blind, multi-centre, randomised controlled trial recruited 201 older people with dementia. The main outcome measures were change in cognitive function and quality of life. An intention-to-treat analysis used analysis of covariance to control for potential variability in baseline measures.\n One hundred and fifteen people were randomised within centres to the intervention group and 86 to the control group. At follow-up the intervention group had significantly improved relative to the control group on the Mini-Mental State Examination (P=0.044), the Alzheimer's Disease Assessment Scale - Cognition (ADAS-Cog) (P=0.014) and Quality of Life - Alzheimer's Disease scales (P=0.028). Using criteria of 4 points or more improvement on the ADAS-Cog the number needed to treat was 6 for the intervention group.\n The results compare favourably with trials of drugs for dementia. CST groups may have worthwhile benefits for many people with dementia.",
"The aim of this project was to assess whether outreach visits would improve the implementation of evidence based clinical practice in the area of falls reduction and stroke prevention in a residential care setting.\n Twenty facilities took part in a randomized controlled trial with a seven month follow-up period. Two outreach visits were delivered by a pharmacist. At the first a summary of the relevant evidence was provided and at the second detailed audit information was provided about fall rates, psychotropic drug prescribing and stroke risk reduction practices (BP monitoring, aspirin and warfarin use) for the facility relevant to the physician. The effect of the interventions was determined via pre- and post-intervention case note audit. Outcomes included change in percentage patients at risk of falling who fell in a three month period prior to follow-up and changes in use of psychotropic medications. Chi-square tests, independent samples t-test, and logistic regression were used in the analysis.\n Data were available from case notes at baseline (n = 897) and seven months follow-up (n = 902), 452 residential care staff were surveyed and 121 physicians were involved with 61 receiving outreach visits. Pre-and post-intervention data were available for 715 participants. There were no differences between the intervention and control groups for the three month fall rate. We were unable to detect statistically significant differences between groups for the psychotropic drug use of the patients before or after the intervention. The exception was significantly greater use of \"as required\" antipsychotics in the intervention group compared with the control group after the pharmacy intervention (RR = 4.95; 95%CI 1.69-14.50). There was no statistically significant difference between groups for the numbers of patients \"at risk of stroke\" on aspirin at follow-up.\n While the strategy was well received by the physicians involved, there was no change in prescribing patterns. Patient care in residential settings is complex and involves contributions from the patient's physician, family and residential care staff. The project highlights challenges of delivering evidence based care in a setting in which there is a paucity of well controlled trial evidence but where significant health outcomes can be attained.",
"To evaluate the potential benefit of immunologic therapy with dialyzable leukocyte extract and psychologic treatment in the form of cognitive-behavioral therapy (CBT) in patients with chronic fatigue syndrome (CFS).\n Immunologic and psychologic treatments were administered to 90 adult patients who fulfilled diagnostic criteria for CFS in a double-blind, randomized, and placebo-controlled study. A four-cell trial design allowed the assessment of benefit from immunologic and psychologic treatment individually or in combination. Outcome was evaluated by measurement of global well-being (visual analogue scales), physical capacity (standardized diaries of daily activities), functional status (Karnofsky performance scale), and psychologic morbidity (Profile of Mood States questionnaire), and cell-mediated immunity was evaluated by peripheral blood T-cell subset analysis and delayed-type hypersensitivity skin testing.\n Neither dialyzable leukocyte extract nor CBT (alone or in combination) provided greater benefit than the nonspecific treatment regimens.\n In this study, patients with CFS did not demonstrate a specific response to immunologic and/or psychologic therapy. The improvement recorded in the group as a whole may reflect both nonspecific treatment effects and a propensity to remission in the natural history of this disorder.",
"Family intervention reduces relapse rates in psychosis. Cognitive-behavioural therapy (CBT) improves positive symptoms but effects on relapse rates are not established.\n To test the effectiveness of CBT and family intervention in reducing relapse, and in improving symptoms and functioning in patients who had recently relapsed with non-affective psychosis.\n A multicentre randomised controlled trial (ISRCTN83557988) with two pathways: those without carers were allocated to treatment as usual or CBT plus treatment as usual, those with carers to treatment as usual, CBT plus treatment as usual or family intervention plus treatment as usual. The CBT and family intervention were focused on relapse prevention for 20 sessions over 9 months.\n A total of 301 patients and 83 carers participated. Primary outcome data were available on 96% of the total sample. The CBT and family intervention had no effects on rates of remission and relapse or on days in hospital at 12 or 24 months. For secondary outcomes, CBT showed a beneficial effect on depression at 24 months and there were no effects for family intervention. In people with carers, CBT significantly improved delusional distress and social functioning. Therapy did not change key psychological processes.\n Generic CBT for psychosis is not indicated for routine relapse prevention in people recovering from a recent relapse of psychosis and should currently be reserved for those with distressing medication-unresponsive positive symptoms. Any CBT targeted at this acute population requires development. The lack of effect of family intervention on relapse may be attributable to the low overall relapse rate in those with carers.",
"To report acceptability, feasibility, and outcome data from a randomized clinical trial (RCT) of a brief intervention for caregivers of children newly diagnosed with cancer.\n Eighty-one families were randomly assigned following collection of baseline data to Intervention or Treatment as Usual (TAU). Recruitment and retention rates and progression through the protocol were tracked. Measures of state anxiety and posttraumatic stress symptoms served as outcomes.\n Difficulties enrolling participants included a high percentage of newly diagnosed families failing to meet inclusion criteria (40%) and an unexpectedly low participation rate (23%). However, movement through the protocol was generally completed in a timely manner and those completing the intervention provided positive feedback. Outcome data showed no significant differences between the arms of the RCT.\n There are many challenges inherent in conducting a RCT shortly after cancer diagnosis. Consideration of alternative research designs and optimal timing for interventions are essential next steps.",
"Adherence to recommended aerosol medicines and airway clearance techniques (ACT) for children with cystic fibrosis (CF) requires self-management skills. A multi-centre, randomized, controlled trial was conducted to investigate the effectiveness of a self-management education programme called 'Airways' for six- to 11-year old children with CF and their caregivers. Assessments were conducted immediately before and after the intervention period, and six and 12 months after the post-intervention assessment. The pen and paper education programme was completed by the child and caregiver together at home. Participants in the intervention and control groups had similar baseline characteristics. A per-protocol analysis was conducted and for variables that changed significantly, an additional intention-to-treat analysis was performed that included data from participants in the intervention group who withdrew from the study during the intervention period. The intervention group increased the percentage of prescribed aerosols taken (P < 0.001) and this was maintained at 12-month follow-up (P < 0.001). There was no change in the percentage of prescribed ACT performed, although when the child was unwell, caregivers in the intervention group increased the frequency and/or duration of ACT (P = 0.028) in the per-protocol analysis but not in the intention-to-treat analysis. Children in the intervention group increased their knowledge of ACT (P < 0.001) which was maintained at 12-month follow-up (P < 0.001) and felt more positively about their chest treatment regimens immediately following the intervention (P = 0.017) but not at 12-month follow-up. There were no significant changes in the control group for these variables over time. No significant changes occurred in the caregivers' reports of self-management behaviours and self-efficacy in either group. The positive results suggest that 'Airways' is a valuable educational tool for primary school-aged children with CF and their caregiver.",
"Cystic fibrosis (CF) remains the most common genetically inherited disease in the white population and its prognosis is affected by nutritional status. Adults with the disease are now surviving longer and new strategies are required to ensure that they maintain optimal nutrition. This article reports preliminary data from a randomized controlled trial of a 10-week home-based behavioral nutrition intervention, \"Eat Well with CF.\" Outcome measures of weight change over 6 and 12 months and changes in CF-specific nutrition knowledge score, self-efficacy score, reported dietary fat intake and health-related quality-of-life score were compared between the intervention group (n=34) and a standard care control group (n=34). The hypotheses to be tested were that adults with CF completing \"Eat Well with CF\" would have an improved nutritional status, improvement in specific nutrition knowledge, and an improvement in self-efficacy regarding their ability to cope with a special diet, compared to those receiving standard care. There were substantial improvements in the intervention group's specific CF nutrition knowledge score, self-efficacy score, and reported fat intake compared to control, but no substantial change in body mass index or health-related quality of life over time. Home-based nutrition education incorporating behavioral strategies can be an effective way to support adults with CF, enabling improvement in self-management skills in relation to diet and pancreatic enzyme replacement therapy. This study revealed gaps in basic nutrition knowledge and skills, inadequate knowledge of diet-disease links and pancreatic enzyme replacement therapy. These need to be identified when subjects progress from pediatric to adult care, and programs such as \"Eat Well with CF\" are a useful adjunct for registered dietitians trying to manage this diverse but growing population.",
"Cognitive problems in multiple sclerosis are common but any possible benefits of treatment remain uncertain. The aim of the study was to evaluate the benefits of providing a psychology service, including cognitive assessment and intervention, to patients with multiple sclerosis.\n The study was a single blind randomised controlled trial. A total of 240 patients with clinically definite, laboratory supported, or clinically probable multiple sclerosis were recruited from an multiple sclerosis management clinic and assessed on a brief screening battery. They were randomised into three groups. The control group received no further intervention. The assessment group received a detailed cognitive assessment, the result of which was fed back to staff involved in the patients' care. The treatment group received the same detailed cognitive assessment and a treatment programme designed to help reduce the impact of their cognitive problems. Patients were followed up 4 and 8 months later on the general health questionnaire (GHQ-28), extended activities of daily living scale, SF-36, everyday memory questionnaire, dysexecutive syndrome questionnaire, and memory aids questionnaire.\n The three groups were compared on the outcome measures at 4 and 8 months after recruitment. There were few significant differences between the groups and those that occurred favoured the control group. Overall, the results showed no effect of the interventions on mood, quality of life, subjective cognitive impairment or independence.\n The study failed to detect any significant effects of cognitive assessment or cognitive intervention in this cohort of people with multiple sclerosis.",
"To test the hypothesis that group cognitive behavioural therapy (CBT) will produce an effective and cost-effective management strategy for patients in primary care with chronic fatigue syndrome/myalgic encephalopathy (CFS/ME).\n A double-blind, randomised controlled trial was adopted with three arms. Outcomes were assessed at baseline and 6 and 12 months after first assessment and results were analysed on an intention-to-treat basis.\n A health psychology department for the management of chronic illness in a general hospital in Bristol, UK.\n Adults with a diagnosis of CFS/ME referred by their GP.\n The three interventions were group CBT incorporating graded activity scheduling, education and support group (EAS) and standard medical care (SMC).\n The primary outcome measure was the Short Form with 36 Items (SF-36) physical and mental health summary scales. Other outcome measures included the Chalder fatigue scale, Hospital Anxiety and Depression Scale, General Health Questionnaire, physical function (shuttles walked, walking speed and perceived fatigue), health utilities index and cognitive function (mood, recall and reaction times).\n A total of 153 patients were recruited to the trial and 52 were randomised to receive CBT, 50 to EAS and 51 to SMC. Twelve patients failed to attend for the 12-month follow-up and 19 patients attended one follow-up, but not both. The sample was found to be representative of the patient group and the characteristics of the three groups were similar at baseline. Three outcome measures, SF-36 mental health score, Chalder fatigue scale and walking speed, showed statistically significant differences between the groups. Patients in the CBT group had significantly higher mental health scores [difference +4.35, 95% confidence interval (CI) +0.72 to +7.97, p = 0.019], less fatigue (difference -2.61, 95% CI -4.92 to -0.30, p = 0.027) and were able to walk faster (difference +2.83 shuttles, 95% CI +1.12 to +5.53, p = 0.0013) than patients in the SMC group. CBT patients also walked faster and were less fatigued than those randomised to EAS (walking speed: difference +1.77, 95% CI +0.025 to +3.51, p = 0.047; fatigue: difference -3.16, 95% CI -5.59 to -0.74, p = 0.011). Overall, no other statistically significant difference across the groups was found, although for many measures a trend towards an improved outcome with CBT was seen. Except for walking speed, which, on average, increased by +0.87 shuttles (95% CI +0.09 to +1.65, p = 0.029) between the 6- and 12-month follow-ups, the scores were similar at 6 and 12 months. At baseline, 30% of patients had an SF-36 physical score within the normal range and 52% had an SF-36 mental health score in the normal range. At 12 months, the physical score was in the normal range for 46% of the CBT group, 26% of the EAS group and 44% of SMC patients. For mental health score the percentages were CBT 74%, EAS 67% and SMC 70%. Of the CBT group, 32% showed at least a 15% increase in physical function and 64% achieved a similar improvement in their mental health. For the EAS and SMC groups, this improvement in physical and mental health was achieved for 40 and 60% (EAS) and 49 and 53% (SMC), respectively. The cost-effectiveness of the intervention proved very difficult to assess and did not yield reliable conclusions.\n Group CBT did not achieve the expected change in the primary outcome measure as a significant number did not achieve scores within the normal range post-intervention. The treatment did not return a significant number of subjects to within the normal range on this domain; however, significant improvements were evident in some areas. Group CBT was effective in treating symptoms of fatigue, mood and physical fitness in CFS/ME. It was found to be as effective as trials using individual therapy in these domains. However, it did not bring about improvement in cognitive function or quality of life. There was also evidence of improvement in the EAS group, which indicates that there is limited value in the non-specific effects of therapy. Further research is needed to develop better outcome measures, assessments of the broader costs of the illness and a clearer picture of the characteristics best fitted to this type of intervention.",
"Little is known about the medium-term durability of cognitive-behavioural therapy (CBT) in a community sample of people with schizophrenia.\n To investigate whether brief CBT produces clinically important outcomes in relation to recovery, symptom burden and readmission to hospital in people with schizophrenia at 1-year follow-up.\n Participants (336 of 422 randomised at baseline) were followed up at a mean of 388 days (s.d. = 53) by raters masked to treatment allocation (CBT or usual care).\n At 1-year follow-up, participants who received CBT had significantly more insight (P = 0.021) and significantly fewer negative symptoms (P = 0.002). Brief therapy protected against depression with improving insight and against relapse; significantly reduced time spent in hospital for those who did relapse and delayed time to admission. It did not improve psychotic symptoms or occupational recovery, nor have a lasting effect on overall symptoms or depression at follow-up.\n Mental health nurses should be trained in brief CBT for schizophrenia to supplement case management, family interventions and expert therapy for treatment resistance."
] |
Currently no clear evidence exists on the best psychological interventions to help people with CF and their carers manage the disease. Trials of interventions to improve adherence to treatment are needed. Multicentre approaches, with consequent funding implications, will increase the sample size of trials and enhance the power and precision of their findings.
|
CD005307
|
[
"9722255",
"12969999",
"2267922",
"10212082",
"9864001",
"16387583",
"16556691",
"10095821",
"7638372",
"2221590",
"9024451",
"15363007",
"9364183",
"7359263",
"8924134",
"20197425",
"16799799",
"9771245",
"10335000"
] |
[
"Efficacy of sequential early systemic and inhaled corticosteroid therapy in the prevention of chronic lung disease of prematurity.",
"A randomized controlled trial of inhaled flunisolide in the management of acute asthma in children.",
"Placebo controlled trial of systemic corticosteroids in acute childhood asthma.",
"Randomised controlled study of early use of inhaled corticosteroid in preterm infants with respiratory distress syndrome.",
"An inhaled steroid improves markers of airway inflammation in patients with mild asthma.",
"Response profiles to fluticasone and montelukast in mild-to-moderate persistent childhood asthma.",
"Multicenter randomized controlled trial of withdrawal of inhaled corticosteroids in cystic fibrosis.",
"The response to inhaled and oral steroids in patients with stable chronic obstructive pulmonary disease.",
"Comparison of fluticasone propionate and sodium cromoglycate for the treatment of childhood asthma (an open parallel group study).",
"Effect of long-term treatment with an inhaled corticosteroid (budesonide) on airway hyperresponsiveness and clinical asthma in nonsteroid-dependent asthmatics.",
"Effect of corticosteroids on intracranial pressure, computed tomographic findings, and clinical outcome in young children with tuberculous meningitis.",
"Does addition of inhaled steroid to combined bronchodilator therapy affect health status in patients with COPD?",
"The efficacy of inhaled corticosteroids in the management of non asthmatic chronic airflow obstruction.",
"Corticosteroids in status asthmaticus.",
"Early corticosteroid use in acute exacerbations of chronic airflow obstruction.",
"Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids.",
"Do inhaled corticosteroids impair long-term growth in prepubertal cystic fibrosis patients?",
"Treatment of acute asthmatic exacerbations with an increased dose of inhaled steroid.",
"Randomised trial of an inhaled beta2 agonist, inhaled corticosteroid and their combination in the treatment of asthma."
] |
[
"In order to assess the efficacy of a combination of systemic and nebulized corticosteroids in reducing the incidence and severity of chronic lung disease (CLD) in very low birthweight (VLBW) infants, 60 ventilator-dependent infants < or = 1500 g were randomly assigned to receive either steroids or placebo as of 7 d. The steroid group (n = 30, GA = 25.8 +/- 1.6 weeks, BW = 731 +/- 147 g) received systemic dexamethasone for 3 d, followed by nebulized budesonide for 18 d. Control infants (n = 30, GA = 25.9 +/- 1.8 weeks, BW = 796 +/- 199 g) received systemic and inhaled saline. Steroid-treated infants required less ventilatory support between 9 and 17 d (p < 0.01), and had greater lung compliance at 10 d (p = 0.01), but not subsequently. CLD incidence at 36 weeks was 45.5% vs 56.0% in controls, and fewer steroid-treated infants required dexamethasone rescue (23.3% vs 56.7%, p = 0.017). Survival to discharge was similar (73.3% vs 83.3%), as were the durations of mechanical ventilation, supplemental oxygen use, and hospitalization. Tracheal effluent elastase/albumin ratios and serum cortisol values did not differ between groups, and no adverse effects were noted. We conclude that early dexamethasone administration was associated with improved pulmonary function, which was not sustained with nebulized budesonide. However, the steroid regimen studied reduced the need for dexamethasone rescue in infants with CLD.",
"Inhaled corticosteroids (ICS) may provide benefit in the therapy of acute asthma. The purpose of this study was to test the hypothesis that ICS are as effective as oral corticosteroids (OCS) in the management of acute childhood asthma.\n A randomized, masked, placebo-controlled study was conducted in children aged 6 to 16 years seeking emergent care for an acute exacerbation of asthma. Patients were randomized into one of two groups: group 1 (OCS), oral prednisone, 2 mg/kg (maximum of 60 mg/d) for 7 days, and placebo pressurized metered-dose inhaler with valved holding chamber, four inhalations bid; and group 2 (ICS), flunisolide, four inhalations (1 mg) bid for 7 days, and daily placebo tablets. Spirometry (FEV(1)) was performed at baseline, day 3, and day 7 of the study. A symptom diary and twice-daily peak expiratory flow were recorded.\n A total of 58 subjects receiving ICS (n = 27) or OCS (n = 28) were enrolled. Baseline asthma severity, race, gender, and age were balanced between the two groups. chi(2) showed no significant difference in symptom severity between the two groups at any time during the study. FEV(1) percentage of predicted was lower in the ICS group on day 3 (65% vs 78%, p = 0.03) and on day 7 (77% vs 95%, p = 0.002).\n ICS were found to be useful in the management of acute asthma in children; however, spirometry data suggested a more rapid resolution of asthma with OCS.",
"In a randomised controlled trial 38 asthmatic children aged 2-11 yr who had not received regular oral or inhaled steroids during the previous year, were treated with a standard regime of nebulised salbutamol and intravenous aminophylline plus either hydrocortisone and oral prednisolone for 5 days, or placebo. The children were observed throughout their hospital stay and for 3 months afterwards. There was a greater fall in heart rates in the steroid treated group on the second day of treatment (mean diff. 16 beats/min) and at discharge (mean diff. 13 beats/min); p less than 0.025. Peak Expiratory Flow Rates recorded in 26 children, 13 in each group, showed more improvement on day 2 in those given steroids (mean diff 16% predicted); p less than 0.05. This difference was not apparent at discharge but 9 children treated with steroids were clinically wheeze-free when they left hospital compared with 3 in the placebo group, p less than 0.05. There were no differences in respiratory rate, pulsus paradoxus and arterial oxygen saturation. Trends in duration of hospital stay and relapse rate during the succeeding 3 months favoured active treatment. These findings support the use of systemic corticosteroids in addition to high dose bronchodilators to treat 'non steroid dependent' children hospitalised with acute severe asthma.",
"To investigate the therapeutic efficacy of inhaled fluticasone propionate, started on day 1 of age, on ventilated preterm infants with respiratory distress syndrome.\n Starting within 24 hours of age, ventilated preterm infants (gestation < 32 weeks, birthweight < 1.5 kg) with respiratory distress syndrome were given a 14 day course (two puffs, 12 hourly) of either fluticasone propionate (250 microg/puff) (group 1, n=27) or placebo (group 2, n=26) with a metered dose inhaler-spacer device. Response to treatment was assessed by the rate of successful extubation by days 7 and 14 of age, changes in respiratory system mechanics, death, occurrence of chronic lung disease, and other neonatal complications.\n More infants in the treatment group were successfully extubated by 14 days of age than those in the placebo group (17/27 vs 8/26; p = 0.038). The treated infants also showed a more significant improvement in respiratory system compliance during the first 14 days of life. The two groups, however, did not differ significantly in their need for systemic steroids after day 14 of age, death, or the occurrence of chronic lung disease. The treatment was not associated with any increase in neonatal complications, including those attributable to steroid induced side effects.\n These results provide preliminary evidence that early treatment with inhaled corticosteroids may be beneficial to ventilated preterm infants with respiratory distress. Further study of its use in a large scale randomised trial is warranted.",
"Airway inflammation can be demonstrated in mildly asthmatic patients who are not treated with inhaled steroids. Current guidelines recommend that inhaled steroids should be introduced in mild asthmatics who use an inhaled beta2-agonist more than once daily. It was postulated that inhaled steroids can have anti-inflammatory effects in patients with even milder disease. The effect of 4 weeks of treatment with budesonide (800 microg twice daily by Turbohaler) was studied in 10 steroid-naive mildly asthmatic patients (forced expiratory volume in one second (FEV1) = 96+/-1.4% predicted) who required an inhaled beta2-agonist less than one puff daily, in a double-blind, placebo-controlled, crossover fashion. Spirometry, exhaled nitric oxide (NO), bronchial responsiveness (provocative concentration causing a 20% fall in FEV1 (PC20)), and sputum induction were performed before and after each treatment period. Following budesonide treatment, there were significant improvements in FEV1, and PC20, in association with a significant reduction in the percentage of eosinophils in induced sputum. Exhaled NO levels tended towards reduction, but the change was nonsignificant. There were also nonsignificant reductions in sputum eosinophil cationic protein and tumour necrosis factor-alpha levels. In conclusion inhaled budesonide can lead to improvements in noninvasive markers of airway inflammation, in association with a small improvement in lung function, even in mildly asthmatic patients who require an inhaled beta2-agonist less than once daily. This suggests a potential benefit of inhaled corticosteroids, even in relatively asymptomatic asthma.",
"Outcome data are needed to base recommendations for controller asthma medication use in school-aged children.\n We sought to determine intraindividual and interindividual response profiles and predictors of response to an inhaled corticosteroid (ICS) and a leukotriene receptor antagonist (LTRA).\n An ICS, fluticasone propionate (100 mug twice daily), and an LTRA, montelukast (5-10 mg nightly, age dependent), were administered to children ages 6 to 17 years with mild-to-moderate persistent asthma using only as-needed bronchodilators in a multicenter, double-masked, 2-sequence, 16-week crossover trial. Clinical, pulmonary, and inflammatory responses to these controllers were evaluated.\n Improvements in most clinical asthma control measures occurred with both controllers. However, clinical outcomes (asthma control days [ACDs], the validated Asthma Control Questionnaire, and albuterol use), pulmonary responses (FEV(1)/forced vital capacity, peak expiratory flow variability, morning peak expiratory flow, and measures of impedance), and inflammatory biomarkers (exhaled nitric oxide [eNO]) improved significantly more with fluticasone than with montelukast treatment. eNO was both a predictor of ACDs (P = .011) and a response indicator (P = .003) in discriminating the difference in ACD response between fluticasone and montelukast.\n The more favorable clinical, pulmonary, and inflammatory responses to an ICS than to an LTRA provide pediatric-based group evidence to support ICSs as the preferred first-line therapy for mild-to-moderate persistent asthma in children. eNO, as a predictor of response, might help to identify individual children not receiving controller medication who achieve a greater improvement in ACDs with an ICS compared with an LTRA.",
"Lung inflammation and injury is critical in cystic fibrosis. An ideal antiinflammatory agent has not been identified but inhaled corticosteroids are widely used despite lack of evidence.\n To test the safety of withdrawal of inhaled corticosteroids with the hypothesis this would not be associated with an earlier onset of acute chest exacerbations.\n Multicenter randomized double-blind placebo-controlled trial in 18 pediatric and adult UK centers. Eligibility criteria included age>6.0 yr, FEV1>or=40% predicted, and corticosteroid use>3 mo. During the 2-mo run-in period, all patients received fluticasone; they then took either fluticasone or placebo for 6 mo.\n Fluticasone group: n=84, median age 14.6 yr, mean (SD) FEV1 76% (18); placebo group: n=87, median age 15.8 yr, mean (SD) FEV1 76% (18). There was no difference in time to first exacerbation (primary outcome) with hazard ratio (95% confidence interval) of 1.07 (0.68 to 1.70) for fluticasone versus placebo. There was no effect of age, atopy, corticosteroid dose, FEV1, or Pseudomonas aeruginosa status. There was no change in lung function or differences in antibiotic or rescue bronchodilator use. Fewer patients in the fluticasone group withdrew from the study due to lung-related adverse events (9 vs. 15%); with a relative risk (95% confidence interval) of 0.59 (0.23-1.48) fluticasone versus placebo.\n In this study population (applicable to 40% of patients with cystic fibrosis in the UK), it appears safe to consider stopping inhaled corticosteroids. Potential advantages will be to reduce the drug burden on patients, reduce adverse effects, and make financial savings.",
"A significant minority of patients with COPD have favourable response to corticosteroid treatment. In addition, the benefit of corticosteroid treatment may be outweighed by the side-effects. Long-term administration of inhaled steroids is a safe means of treatment. However, only a few studies have addressed the role of inhaled steroids in patients with COPD, with conflicting results.\n Forty-four patients with stable COPD were defined as 'responders to bronchodilators' (increase in FEV1 > or = 20% following administration of beta 2-agonist) (group A), and 124 as 'non-responders to bronchodilators' (group B). All patients were randomized to receive a 6-week course of either a daily dose of 800 micrograms of inhaled budesonide or placebo, separated by 4 weeks when no medication was taken; were randomized again to receive a 6-week course of either 1600 micrograms day-1 of inhaled budesonide, or 800 micrograms day-1 of inhaled budesonide plus placebo; and were randomized once again to receive a 6-week course of either 40 mg day-1 of prednisone or placebo. All stages were performed in a double-blind cross-over design.\n Following administration of 800 micrograms day-1 of inhaled budesonide, there was an increase in the mean FEV1 from 1.40 +/- 0.20 to 1.92 +/- 0.22 L (P < 0.001) and a significant decrease in inhaled beta 2 agonist consumption in group A. These changes remained almost stable during the increased dose of inhaled budesonide or during prednisone treatment. The mean FEV1 did not change during the placebo period, or in group B in either treatments.\n Treatment with inhaled steroids improved spirometry data and inhaled beta 2-agonist consumption in about one-quarter of patients with stable COPD, and this rate increased to about three-quarters in patients who responded to beta 2-agonist inhalation. There was no additional benefit in using a higher dose of inhaled budesonide or prednisone.",
"Inhaled corticosteroids are highly effective in the treatment of asthma at all ages and their use in younger children is increasing. As concerns exist about the long-term systemic side-effects of high dose inhaled corticosteroids, current guidelines continue to recommend sodium cromoglycate (SCG) as first line regular medication for children with frequent symptoms. Few published studies have compared the safety and efficacy of inhaled corticosteroids with SCG in children. This study compares SCG with the new inhaled corticosteroid, fluticasone propionate (FP), which has theoretical advantages over other currently available corticosteroids due to its negligible oral bioavailability. This was a randomized, open, multi-centre, parallel group comparison of 50 micrograms FP twice daily and 20 mg SCG four times daily over 8 weeks, preceded by a 2-week baseline period. Sixty-two general practices and two hospital centres enrolled 225 asthmatic children aged 4-12 years (110 received FP; 115 received SCG). Outcome measures improved in both groups, with a significant difference in favour of FP for the key variables of mean morning and evening % predicted PEFR and % of symptom-free days and nights. No significant difference was observed for FEV1, or relief medication use. Two children taking FP and 10 children taking SCG withdrew because of adverse events. This study showed that low dose FP was effective and superior to SCG in young children with mild-moderate asthma. Safety studies of longer duration are needed before changing the current recommendations for inhaled corticosteroid therapy.",
"Several short-term studies have shown that inhaled steroids can reduce airway hyper-responsiveness in asthma. To evaluate whether prolonged treatment can bring about full recovery, this double-blind, randomized, controlled trial examined the effect of budesonide, 400 micrograms daily for 1 yr, on airway hyperresponsiveness. The time course and characteristics of improvements and associated changes in clinical asthma severity were also evaluated. Thirty-two stable adult asthmatics, requiring bronchodilators alone, were selected. Before and monthly throughout the study, airway responsiveness to methacholine was measured and clinical asthma severity assessed by questionnaire, daily bronchodilator use, and number of asthma exacerbations. Patients receiving budesonide showed a fourfold mean improvement in airway responsiveness compared with those receiving placebo (p less than 0.0005), whose responsiveness remained very stable. Fifteen of the 16 budesonide subjects improved and 5 returned to the normal range. Largest improvements occurred during the first 3 months but, in some, were still progressing slowly at 1 yr. Improvements in responsiveness were accompanied by significant improvements in asthma symptoms, bronchodilator use, and number of asthma exacerbations. The results show that regular, prolonged use of inhaled steroid can produce marked improvements in airway hyperresponsiveness, sometimes with full resolution, and these improvements are accompanied by clinically significant improvements in clinical asthma.",
"To study the effect of highdose prednisone on intracranial pressure (ICP), cranial computed tomographic (CT) findings, and clinical outcome in young children with moderate to severe tuberculous meningitis (TBM).\n Prospective, controlled, randomized study.\n Continuous lumbar, cerebrospinal fluid pressure monitoring and contrasted CT scanning were performed in 141 consecutive children with TBM at admission. All children were then randomly allocated to a nonsteroid group (71 children) or a steroid group (70 children) who received prednisone (first 16 children, 2 mg/kg per day; next 54 children, 4 mg/kg per day) for the first month of treatment. ICP monitoring and CT scanning were repeated regularly, and clinical outcome was assessed after 6 months of antituberculosis treatment.\n No statistically significant difference in ICP or the degree of hydrocephalus (as demonstrated by CT scan) was found between the steroid and nonsteroid groups after the first month of treatment. Basal ganglia infarcts developed in 16% of children in the steroid group and 24% in the nonsteroid group during the first month of treatment. Neither this incidence nor the eventual size of infarcts present at admission differed significantly between the two treatment groups. Single or multiple tuberculomas were seen on the first CT scans of 7 children (5%), whereas tuberculomas developed in 11 children (8%) at treatment. Both the response of the tuberculomas to treatment and the incidence of new tuberculomas were significantly improved by steroid therapy. Basal enhancement was also significantly less in the steroid group after 1 month of treatment. Steroids lowered mortality in stage III TBM significantly. Similarly, more surviving children in the steroid group had IQs of greater than 75 than did the those in the nonsteroid group. No significant difference was found in the incidence of motor deficit, blindness, or deafness.\n Corticosteroids significantly improved the survival rate and intellectual outcome of children with TBM. Enhanced resolution of the basal exudate and tuberculomas by steroids was shown by serial CT scanning. Corticosteroids did not affect ICP or the incidence of basal ganglia infarction significantly.",
"Withdrawal of corticosteroid is associated with a deterioration of health status in COPD. In this study the aim was to determine whether high dose inhaled corticosteroid improves quality of life in patients with COPD.\n In total, 38 male patients with moderate COPD were included in the study. Baseline quality of life scores were determined using a Turkish version of the St George's Respiratory Questionnaire (SGRQ). Patients were randomly divided into two groups. Group 1 consisted of 20 patients who received existing bronchodilator therapy plus inhaled corticosteroid (800 micro g budesonide) for 12 weeks, while 18 patients in group 2 received bronchodilator and placebo. The SGRQ was repeated after the treatment period.\n All patients were male and mean age was 67 +/- 8.2 years. Symptom, activity, impact, and total scores were assessed and a difference of four units with treatment was considered to be clinically significant. Total score and activity score were decreased by six units and eight units, respectively, in the placebo group while symptom and impact scores did not change significantly. Total scores and the three component scores improved significantly in the corticosteroid group compared to the placebo group (Deltatotal score: -22 in corticosteroid group, -6 in placebo group, P < 0.01).\n Inhaled corticosteroid improved quality of life scores in patients with COPD, without significant improvement in airflow obstruction parameters. Since improvement of health status is one of the important aims in COPD treatment, use of inhaled corticosteroids should be considered from this perspective.",
"The aims of this investigation were to evaluate the efficacy of regular inhaled beclomethasone in the control of symptoms and lung function with non-asthmatic smoking related obstructive pulmonary disease and to evaluate the relationship between clinical responses to a short course of oral prednisone and longer term outcomes using inhaled steroid.\n The study was a randomised, double blind, placebo controlled, crossover investigation in 18 patients. The active treatment was inhaled beclomethasone 1000 micrograms given twice daily for three months by metered dose inhaler. At the end of each treatment period, patients received oral prednisone 30 mg/day for ten days. The two treatment phases were separated by a one month washout interval. Peak flow rates, symptom scores and \"rescue\" bronchodilator use were recorded twice daily. Lung function (FEV1, FVC and lung volumes) and bronchial hyperresponsiveness (PC20 methacholine) were measured at monthly visits. The number of exacerbations requiring intervention therapy were also recorded.\n There were no consistent benefits attributable to beclomethasone. Lung function was not significantly better as a result of active treatment. Sputum production improved but other symptom scores were similar during active and placebo therapy. Three patients exhibited an increase in FEV1 of 15% or more during active treatment but did not do so when oral prednisone was administered immediately after the period of placebo treatment. A further three patients showed an improvement in FEV1 of 15% or more with oral prednisone but failed to improve during treatment with inhaled beclomethasone. The predictive value of the \"trial of steroid\" was 0% and 81.3% for positive and negative outcomes respectively.\n Our results indicate that in non-asthmatic chronic obstructive pulmonary disease inhaled corticosteroid fails to achieve significant improvements in either lung function or symptoms. The response to a \"trial of steroid\" using oral prednisone is not clinically helpful in selecting the small number of patients who may subsequently benefit from this form of therapy.",
"Nineteen children who were not steroid dependent and were hospitalized in status asthmaticus were studied to evaluate the effect of corticosteroids. They were randomized into two groups. Each group received salbutamol inhalations and intravenous aminophylline therapy. One group received 7 mg/kg hydrocortisone intravenously every six hours; the other group served as a control. Each group showed significant improvement in clinical score and peak expiratory flow rate after 36 hours; there was no statistical difference in the degree of improvement. Six of ten steroid-treated children and six of nine controls achieved a PEFR of 50% predicted by 36 hours. The response to inhaled salbutamol was similar in each group. The results show that in the first 36 hours of therapy, corticosteroids have no additive effect on the bronchodilator response of aminophylline and salbutamol and do not hasten the recovery of nonsteroid-dependent children in status asthmaticus. Although the results show that an inhaled sympathomimetic drug is beneficial in status asthmaticus, corticosteroid therapy does not increase the responsiveness of the airways to these agents.",
"To determine the benefit of early steroid use in acute exacerbations of chronic airflow obstruction in the ED, 113 patients with an average age of 66 years, acute or chronic dyspnea, an FEV1 of < 60% and FEV1/FVC ratio of < 60% were included in a randomized, double-blinded, interventional clinical trial. All patients received the same bronchodilator treatment. At 6 hours the steroid- treated group showed a 21.71 L/min improvement in PEFR (P < .05) and 0.14 L improvement in FEV1 (P < .05), while the nonsteroid group showed insignificant improvements of 5.52 L/min and 0.02 L, respectively. Of those patients receiving steroids, 22 achieved > 40% improvements in PEFR by 6 hours and 17 achieved similar results in FEV1, whereas of those not receiving steroids, 13 and 8, respectively, achieved improvements. Within 24 hours of observation in the ED, 16 patients receiving steroids were discharged and none relapsed within 2 weeks. Of those not receiving steroids, only 10 were discharged and 3 returned with exacerbations. Although early response to steroids in chronic airflow obstruction is variable, the overall medical and cost benefits justify their early use in acute exacerbations.",
"For children who have uncontrolled asthma despite the use of low-dose inhaled corticosteroids (ICS), evidence to guide step-up therapy is lacking.\n We randomly assigned 182 children (6 to 17 years of age), who had uncontrolled asthma while receiving 100 microg of fluticasone twice daily, to receive each of three blinded step-up therapies in random order for 16 weeks: 250 microg of fluticasone twice daily (ICS step-up), 100 microg of fluticasone plus 50 microg of a long-acting beta-agonist twice daily (LABA step-up), or 100 microg of fluticasone twice daily plus 5 or 10 mg of a leukotriene-receptor antagonist daily (LTRA step-up). We used a triple-crossover design and a composite of three outcomes (exacerbations, asthma-control days, and the forced expiratory volume in 1 second) to determine whether the frequency of a differential response to the step-up regimens was more than 25%.\n A differential response occurred in 161 of 165 patients who were evaluated (P<0.001). The response to LABA step-up therapy was most likely to be the best response, as compared with responses to LTRA step-up (relative probability, 1.6; 95% confidence interval [CI], 1.1 to 2.3; P=0.004) and ICS step-up (relative probability, 1.7; 95% CI, 1.2 to 2.4; P=0.002). Higher scores on the Asthma Control Test before randomization (indicating better control at baseline) predicted a better response to LABA step-up (P=0.009). White race predicted a better response to LABA step-up, whereas black patients were least likely to have a best response to LTRA step-up (P=0.005).\n Nearly all the children had a differential response to each step-up therapy. LABA step-up was significantly more likely to provide the best response than either ICS or LTRA step-up. However, many children had a best response to ICS or LTRA step-up therapy, highlighting the need to regularly monitor and appropriately adjust each child's asthma therapy. (ClinicalTrials.gov number, NCT00395304.)\n 2010 Massachusetts Medical Society",
"Despite absence of clear proof of efficacy, the use of inhaled corticosteroids (ICS) is widespread in cystic fibrosis (CF) patients. Therefore, the effect of ICS on lung function and other clinical variables was studied in 27 prepubertal CF children with mild to moderate lung disease. In a prospective double-blind case-controlled study, fluticasone propionate 500 microg or placebo were administered twice daily during 12 months. The mean (standard error of the mean, SEM) patient age was 8.2 (0.6) years in the placebo group and 9.0 (0.5) years in the fluticasone group. The mean (SEM) forced expiratory volume in 1 s (FEV(1)) was 91% (4%) in the placebo group and 86% (4%) in the fluticasone group. There was no statistically significant difference in the evolution of lung function and the number of respiratory exacerbations between groups. However, longitudinal growth in fluticasone patients was significantly slower than in placebo patients: 3.96 (0.29) cm versus 5.49 (0.38) cm [p<0.005, analysis of variance (ANOVA)] over the 12-month study duration. This resulted in a significant change in height standard deviation score (SDS) of -0.38 (0.09) in the fluticasone group versus -0.01 (0.07) in the placebo group (p<0.003, ANOVA). No catch-up growth was noted 1-2 years after discontinuation of inhaled steroids. The use of high-dose ICS in CF patients with mild lung disease may lead to persistent growth impairment.",
"To investigate the efficacy of an increased dose of inhaled steroid used within the context of an asthma self management plan for treating exacerbations of asthma.\n Randomised, double blind, placebo controlled, crossover trial.\n Twenty eight children aged 6-14 years with asthma of mild to moderate severity were studied for six months. Eighteen pairs of exacerbations were available for analysis, during which subjects took an increased dose of inhaled steroids or continued on the same dose.\n There was no significant difference between increasing inhaled steroids or placebo on morning or evening peak expiratory flow rates (PEFRs), diurnal peak flow variability, or symptom scores in the two weeks following an asthma exacerbation. Difference (95% confidence intervals) in baseline PEFR on days 1-3 were 3.4% (-3.5% to 10.4%) and -0.9% (-4.7% to 2.9%) for inhaled steroid and placebo, respectively. Spirometric function and the parents' opinion of the effectiveness of asthma medications at each exacerbation were also not significantly different between inhaled steroid or placebo.\n This study suggests that increasing the dose of inhaled steroids at the onset of an exacerbation of asthma is ineffective and should not be included in asthma self management plans.",
"Although many asthmatic patients are treated with a combination of beta2 agonist and corticosteroid inhalers, the clinical effects of combining the drugs are unknown. Studies on the early asthmatic response to allergen suggest that beta2 agonists may reduce the benefit of inhaled corticosteroids. A study of the effects of combining the drugs on asthma control was undertaken.\n Sixty one subjects with mild to moderate asthma were randomised to a double blind crossover comparison of inhaled budesonide (200-400 microg twice daily), terbutaline (500-1000 microg four times daily), combined treatment, and placebo. Each treatment was given for six weeks following a four week washout period. Ipratropium was used for symptom relief. Treatments were ranked from worst (1) to best (4) based on need for oral steroid, mean morning peak flow, nocturnal awakening, ipratropium use, and asthma symptoms. Lung function and bronchial hyperresponsiveness were measured before and after each treatment.\n Evaluable data for all four treatments were obtained from 47 subjects. The mean rank of each treatment was: placebo = 2.05; terbutaline = 2.13; budesonide = 2.48; combined treatment = 3.34. Combined treatment was ranked significantly better than any other treatment (p<0.01). Mean (95% CI) morning and evening peak flows were 14 (5 to 23) and 24 (15 to 34) l/min higher, respectively, during combined treatment than during budesonide, and 27 (17 to 37) and 15 (7 to 23) l/min higher than during terbutaline. Asthma symptoms tended to be least frequent during combined treatment but were not significantly different from budesonide alone. There was no significant difference between combined treatment and budesonide alone for lung function and bronchial hyperresponsiveness.\n In this group of mild to moderate asthmatic subjects the combination of beta2 agonist and corticosteroid gave better asthma control than either treatment alone. There was no evidence that regular beta2 agonist treatment impaired the beneficial effect of inhaled corticosteroid."
] |
In steroid-naive patients with mild to moderate airway obstruction, the combination of ICS and LABA does not significantly reduce the risk of patients with exacerbations requiring rescue oral corticosteroids over that achieved with a similar dose of ICS alone. However, it significantly improves lung function, reduces symptoms and marginally decreases rescue ß2-agonist use. Initiation of a higher dose of ICS is more effective at reducing the risk of exacerbations requiring rescue systemic corticosteroids, and of withdrawals, than combination therapy. Although children appeared to respond similarly to adults, no firm conclusions can be drawn regarding combination therapy in steroid-naive children, given the small number of children contributing data.
|
CD009490
|
[
"8427642",
"8502770",
"11933280",
"16750060",
"1760125",
"11905977",
"19374691",
"10645116",
"11933303",
"7960335",
"12964222"
] |
[
"Seeking quality care for patients with pressure ulcers.",
"The role of support surfaces and patient attributes in preventing pressure ulcers in elderly patients.",
"Randomised controlled trial of two pressure-relieving systems.",
"Pressure relieving support surfaces: a randomised evaluation.",
"Prevention of pressure ulcers in elderly nursing home residents: are special support surfaces the answer?",
"A randomized control trial to evaluate pressure-reducing seat cushions for elderly wheelchair users.",
"The impact of pressure ulcer risk assessment on patient outcomes among hospitalised patients.",
"Using telehealth interventions to prevent pressure ulcers in newly injured spinal cord injury patients post-discharge. Results from a pilot study.",
"A clinical evaluation of the Nimbus 3 alternating pressure mattress replacement system.",
"Pressure ulcer prophylaxis in elderly patients using polyurethane foam or Jay wheelchair cushions.",
"Profiling beds versus standard hospital beds: effects on pressure ulcer incidence outcomes."
] |
[
"Improving quality care for patients with pressure ulcers resulted in a two-year intensive effort to educate staff, keep morale high, standardize care plans by stage of ulcer, and participate in a comparison study of two support surfaces (Thera-Pulse, Kinetic Concepts and Geo-Matt, SpanAmerica). When all pressure ulcers were considered, the analysis of covariance revealed no statistically significant difference in the healing of pressure ulcers with respect to type of support surface used (F[1, 78] = 0.35, p > .05). For patients with stage III and IV pressure ulcers, the proportion of patients improving more than 10cm2 was higher in the air-suspension group. There was relatively little difference in the Stage II ulcer patients.",
"Nurses caring for elderly patients often need to select support surfaces that reduce the likelihood of pressure ulcers, but there is little information about the effectiveness of different support surfaces. This randomized trial compared two support surfaces and investigated patient attributes related to the risk of developing a pressure ulcer. Eighty-four elderly patients were nursed on a convoluted or solid foam overlay and assessed three times a week for pressure ulcers. Stepwise Cox proportional hazards regression revealed a statistically significant relationship between the risk of developing a pressure ulcer and the variables mobility and type of support surface.",
"The primary objective of this randomised controlled trial was to determine whether there were significant differences between two pressure-relieving systems. A secondary aim was to investigate whether the availability of extra pressure-relieving equipment would reduce the incidence of ulcers in an acute hospital setting. A total of 141 patients in a care-of-the-elderly unit, who were assessed to have a high risk of developing pressure ulcers using the Waterlow score, were recruited; 70 were nursed using Huntleigh Nimbus 3 in conjunction with the Aura cushion (Group A), and 71 using the Pegasus Cairwave Therapy System in conjunction with the Proactive 2 Seating cushion (Group B). The main outcome measure was visual assessment, supported by a photographic record. There were three main findings: for non-heel ulcers and overall improvement, there was no statistically significant difference between the two products tested; for heel ulcers there was a significant difference (P = 0.019) with more patients healing in Group A than in Group B. The average length of stay of patients who completed the trial was 21.6 days (Group A) and 21.7 days (Group B) for patients completing a live (range 1-121 days) and for patients who died 29.7 days (Group A) and 24.3 days (Group B). Routine monitoring showed that, before the trial, the incidence of hospital-acquired pressure ulcers (Torrance grade 2+) was 0.2%; during the trial, this dropped to 0.13%. The study showed differences in the efficacy of different mattress products; with a sufficiently large study, it is possible to demonstrate statistically significant results. Provision of extra pressure-relieving equipment can reduce the incidence of pressure ulcers but may not influence length of stay.",
"To determine differences between alternating pressure overlays and alternating pressure replacement mattresses with respect to the development of new pressure ulcers, healing of existing pressure ulcers, patient acceptability and cost-effectiveness of the different pressure-relieving surfaces. Also to investigate the specific additional impact of pressure ulcers on patients' well-being.\n A multicentre, randomised, controlled, open, fixed sample, parallel-group trial with equal randomisation was undertaken. The trial used remote, concealed allocation and intention-to-treat (ITT) analysis. The main trial design was supplemented with a qualitative study involving a purposive sample of 20-30 patients who developed pressure ulcers, to assess the impact of the pressure ulcers on their well-being. In addition, a focus group interview was carried out with clinical research nurses, who participated in the PRESSURE (Pressure RElieving Support SUrfaces: a Randomised Evaluation) Trial, to explore the experiences of their role and observations of pressure area care.\n The study took place in 11 hospital-based research centres within six NHS trusts in England.\n Acute and elective patients aged 55 years or older and admitted to vascular, orthopaedic, medical or care of the elderly wards in the previous 24 hours were investigated.\n Patients were randomised to either an alternating pressure overlay or an alternating pressure mattress replacement, with mattress specifications clearly defined to enable the inclusion of centres using products from different manufacturers, and to exclude hybrid mattress systems (which either combine foam or constant low pressure with alternating pressure in one mattress, or can be used as either an overlay or a replacement mattress).\n Development of a new pressure ulcer (grade < or =2, i.e. partial-thickness wound involving epidermis/dermis only) on any skin site. Also healing of existing pressures ulcers, patient acceptability and cost-effectiveness.\n In total, 6155 patients were assessed for eligibility to the trial and 1972 were randomised: 990 to the alternating pressure overlay (989 after one postrandomisation exclusion) and 982 to the alternating pressure mattress replacement. ITT analysis found no statistically significant difference in the proportions of patients developing a new pressure ulcer of grade 2 or above [10.7% overlay patients, 10.3% mattress replacement patients, a difference of 0.4%, 95% confidence interval (CI) -2.3 to 3.1%, p = 0.75]. When logistic regression analysis was used to adjust for minimisation factors and prespecified baseline covariates, there was no difference between the mattresses with respect to the odds of ulceration (odds ratio 0.94, 95% CI 0.68 to 1.29). There was no evidence of a difference between the mattress groups with respect to time to healing (p = 0.86). The Kaplan-Meier estimate of the median time to healing was 20 days for each intervention. More patients allocated overlays requested mattress changes due to dissatisfaction (23.3%) than mattress replacement patients (18.9%, p = 0.02) and more than one-third of patients reporting difficulties associated with movement in bed and getting into or out of bed. There is a higher probability (64%) that alternating mattress replacements are cost-saving; they were associated with lower overall costs (74.50 pounds sterling per patient on average, mainly due to reduced length of stay) and greater benefits (a delay in time to ulceration of 10.64 days on average). Patients' accounts highlighted that the development of a pressure ulcer could be pivotal in the trajectory from illness to recovery, by preventing full recovery or causing varied impacts on their quality of life.\n There is no difference between alternating pressure mattress replacements and overlays in terms of the proportion of patients developing new pressure ulcers; however, alternating pressure mattress replacements are more likely to be cost-saving. The results suggest that when renewing alternating pressure surfaces or ordering equipment within a rental contract, mattress replacements should be specified; however, overlays are acceptable if no replacement mattress is available. Similarly, patient preferences can be supported, without any great increase in risk, if individual patients request an overlay rather than a replacement mattress. Further research could include a randomised controlled trial comparing alternating pressure mattress replacements and high-specification foam mattresses in patients at moderate to high risk; an accurate costing study to understand better how much pressure ulcers cost health and social services in the UK; and trials in higher risk groups of patients. Also future trials should measure time to ulceration as the primary end-point, since this is more informative economically and possibly also from a patient and clinical perspective.",
"This article describes a research study that compared the effectiveness of two pressure-reducing devices in a group of elderly nursing home residents. The results obtained revealed no significant differences between the two devices--an air-filled overlay and a gel mattress--in terms of pressure ulcer incidence, severity, and healing. Several factors contributed to these results and illustrate the problems encountered when preventing pressure ulcer development in a group of elderly, debilitated nursing home residents. These factors include ease of use of the pressure-reducing device, caregiver and facility characteristics, and critical patient variables. Until these variables are addressed, it is impossible for any device to be effective in preventing pressure ulcer development in nursing homes.",
"To determine if the use of pressure-reducing wheelchair cushions for elderly nursing home resident wheelchair users who are at high risk for developing sitting-acquired pressure ulcers would result in a lower incidence rate of pressure ulcers, a greater number of days until ulceration, and lower peak interface pressures compared with the use of convoluted foam cushions over a 12-month period. To determine the feasibility of conducting a subsequent full-scale definitive trial to evaluate the use of pressure-reducing seat cushions for elderly nursing home resident wheelchair users.\n Randomized control trial\n 2200-bed skilled nursing facilities (1 suburban and 1 urban academic medical center)\n 32 male and female at-risk nursing home residents who were wheelchair users > or = 65 years of age. Participants had Braden Scale scores < or = 18, Braden Activity and Mobilitysubscale scores < or = 5, no sitting surface pressure ulcers, and a daily wheelchair sitting tolerance of more than 6 hours. All met criteria for using the ETAC Twin wheelchair.\n Seating evaluation with pressure-mapping and subsequent seating prescription. Subjects were assigned to either a foam (n=17) or pressure-reducing cushion (n=15) group and weekly assessments of skin and pressure ulcer risk were made.\n Incidence of pressure ulcers, days to ulceration, and peak interface pressure.\n At a 95% confidence interval, a 2-tailed analysis showed no differences between the FOAM and pressure-reducing cushion groups for pressure ulcer incidence, total days to pressure ulcer, or initial peak interface pressure. Pressure-reducing cushions were more effective in preventing sitting-acquired (ischial) pressure ulcers (P<.005). Higher interface pressures were associated with a higher incidence of pressure ulcers (P<.001).\n A definitive randomized control multicenter cushion trial is feasible with a sample size of 50 to 100 per study group. In the definitive trial, the definition of sitting-acquired pressure ulcers should be limited to lesions occurring over the ischial tuberosities.",
"To determine whether use of a risk assessment scale reduces nosocomial pressure ulcers.\n There is contradictory evidence concerning the validity of risk assessment scales. The interaction of education, clinical judgement and use of risk assessment scales has not been fully explored. It is not known which of these is most important, nor whether combining them results in better patient care.\n Pretest-posttest comparison.\n A risk assessment scale namely the Braden was implemented in a group of wards after appropriate education and training of staff in addition to mandatory wound care study days. Another group of staff received the same education programme but did not implement the risk assessment scale and a third group carried on with mandatory study days only.\n Nosocomial Pressure Ulcer was reduced in all three groups, but the group that implemented the risk assessment scale showed no significant additional improvement. Allowing for age, gender, medical speciality, level of risk and other factors did not explain this lack of improvement. Clinical judgement seemed to be used by nurses to identify patients at high risk to implement appropriate risk reduction strategies such as use of pressure relieving beds. Clinical judgement was not significantly different from the risk assessment scale score in terms of risk evaluation.\n It is questioned whether the routine use of a risk assessment scale is useful in reducing nosocomial pressure ulcer. It is suggested clinical judgement is as effective as a risk assessment scale in terms of assessing risk (though neither show good sensitivity and specificity) and determining appropriate care.\n Clinical judgement may be as effective as employing a risk assessment scale to assess the risk of pressure ulcers. If this were true it would be simpler and release nursing time for other tasks.",
"To determine which of three approaches to care produces the lowest incidence of pressure ulcers, promotes the most effective care of sores that develop, and leads to the fewest hospitalizations in newly injured patients with spinal cord injury after discharge.\n Spinal cord injury patients (n = 12) were recruited for a telehealth intervention after initial injury, and matched cases were recruited for telephone counseling and standard care groups. Patients were monitored for 6-8 months after discharge.\n The video group had the greatest number of reported and identified pressure ulcers. Differences in health care utilization between the video and telephone telehealth groups were small. The standard care group reported the lowest number of pressure ulcers and lowest frequency of health care utilization. Substantial differences existed in employment rates before and after injury. The video group had the lowest pre-injury rate of employment and the highest post-injury rate of employment.\n Tracking pressure ulcer incidence, particularly stage I sores, is difficult. Self-report is likely to lead to substantial underreporting. Similarly, self-report on health care utilization over extended periods may lead to undercounting of encounters. Telehealth interventions appear to improve ulcer tracking and management of all ulcer occurrences. Video interventions may affect outcomes, such as employment rates, which are not conventionally measured.",
"This study assessed the clinical effectiveness of the Nimbus 3 alternating pressure mattress replacement system (APMRS) on pressure ulcer healing and comfort in subjects > or = 65 years, with at least a Grade 2 ulcer and some mobility problems. Twelve patients in a hospital setting were randomly allocated to the Nimbus 3 or another APMRS, and 20 residents in a nursing home setting to the Nimbus 3 or an alternating pressure mattress overlay. Wound surface area (WSA) (cm2) was recorded twice weekly and comfort once weekly. In the hospital setting, there were no significant differences between groups in the reduction in WSA per day. In the nursing home setting, though subjects on Nimbus 3 had significantly more pressure ulcers at baseline, there were no significant differences between groups in the reduction in WSA per day. Nimbus 3 was statistically more comfortable than control surfaces. The study's sample size has not shown the products were different with regard to clinical effectiveness. However, it might serve as a pilot for a larger, multi-centre RCT aimed at establishing the efficacy of a pressure-relieving (PR) device on pressure ulcer healing.",
"A significantly lower proportion of the patients in the Jay group (25%) experienced pressure ulcer formation during the three months of observation as compared to the foam group (41%). No statistically significant differences were found between groups on the location, severity, or healing duration of the pressure ulcers. Most lesions (65%) were limited to persistent erythema of intact skin, and healed in three to four weeks. Significantly higher proportions of patients in the Jay groups (7%) rejected their cushion because of discomfort as compared to foam (1%). The incidence of pressure ulcers was significantly higher among those patients who experienced peak interface pressures recorded at 60 mmHg or higher, had low Norton scores (< or = 11), or were malnourished.",
"Most standard hospital beds are flat based with a pull-out backrest, resulting in a tendency for the patient to slide down the bed. This study aimed to compare the outcome for patients at high risk of developing pressure ulcers nursed on either this type of bed or an electrically operated, multi-sectioned profiling bed. A total of 100 patients were randomly assigned either to the profiling bed with a pressure-reducing foam mattress (experimental group) or a flat-based bed with an appropriate pressure-redistributing mattress (control group) for a maximum of 10 days. Risk status and pressure damage were assessed daily. Both a patient and a nurse questionnaire were completed. Data from 70 patients who participated in the study for five days or more were included in the analysis. Pressure ulcer incidence was 0% in both groups. All patients (35) in the experimental group were able to maintain a sitting position compared with only 12/35 in the control group (p = 0.0001). While the questionnaire results suggest there were significant differences in postural control and ease of transfer between patients in the two groups, it was not possible to map this to pressure ulcer formation. Poor recruitment into the study was due to the 'blocking' of electric beds by heavily dependent patients who did not meet the inclusion criteria, precluding a significant result in terms of pressure ulcer outcomes. This nurse-led use of the profiling beds was examined alongside the main study to investigate why they were allocated in this way."
] |
There is no conclusive evidence about the superiority of any support surface for the treatment of existing pressure ulcers. Methodological issues included variations in outcomes measured, sample sizes and comparison groups. Many studies had small sample sizes and often there was inadequate description of the intervention, standard care and co-interventions. Individual study results were often inadequately reported, with failure to report variance data common, thus hindering the calculation of mean differences. Some studies did not report P values when reporting on differences in outcomes. In addition, the age of some trials (some being 20 years old), means that other technologies may have superseded those investigated.
Further and rigorous studies are required to address these concerns and to improve the evidence base before firm conclusions can be drawn about the most effective support surfaces to treat pressure ulcers.
|
CD004371
|
[
"16342302",
"17101639",
"17261454",
"14748894",
"15659884",
"11502614",
"15867495",
"6908098",
"9717348",
"7730925"
] |
[
"Effect of intervention through a pharmaceutical care program on patient adherence with prescribed once-daily atorvastatin.",
"Effect of a pharmacy care program on medication adherence and persistence, blood pressure, and low-density lipoprotein cholesterol: a randomized controlled trial.",
"Electronic monitoring of adherence as a tool to improve blood pressure control. A randomized controlled trial.",
"Impact of pharmacist-conducted home visits on the outcomes of lipid-lowering drug therapy.",
"Multidisciplinary HIV adherence intervention: a randomized study.",
"Effect of patient education on adherence to drug treatment for rheumatoid arthritis: a randomised controlled trial.",
"Couple-focused support to improve HIV medication adherence: a randomized controlled trial.",
"Influencing adherence among hypertensives.",
"[Therapeutic compliance in dyslipidemias. A trial of the efficacy of health education].",
"Effects of \"group detailing\" on the prescribing of lipid-lowering drugs: a randomized controlled trial in Swedish primary care."
] |
[
"Correct execution of prescribed dosing regimen(s) is essential for patients to benefit from lipid lowering treatments. The objective of this study was to estimate the effect of a pharmaceutical care program on the adherence of once-daily atorvastatin treatment in patients with elevated cholesterol levels.\n In both linguistic regions of Belgium, two districts were randomized between usual care and a supportive intervention program. Eligible patients included hyperlipemic subjects taking atorvastatin for at least 3 months. 'Adherence' was defined as the proportion of days during which the electronic device record showed that the patient had taken the daily dose. 'Persistence' quantifies how long the treatment is executed.\n A total of 392 patients from 35 pharmacies were included in the intent-to-treat (ITT) analysis of the data (194 patients received intervention and 198 in the control group). The intervention resulted in a 6.5% increase in post-baseline adherence (p < 0.001) mainly driven by a 13% increase in persistence at 1 year (p = 0.002).\n A supportive pharmaceutical care program consisting of review by patient and pharmacist of each patient's electronically compiled dosing history, plus educational reminders, improves patient adherence to the once-daily atorvastatin dosing regimen, mainly by extending persistence.\n Copyright 2005 John Wiley & Sons, Ltd.",
"Poor medication adherence diminishes the health benefits of pharmacotherapies. Elderly patients with coronary risk factors frequently require treatment with multiple medications, placing them at increased risk for nonadherence.\n To test the efficacy of a comprehensive pharmacy care program to improve medication adherence and its associated effects on blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C).\n A multiphase, prospective study with an observational phase and a randomized controlled trial conducted at the Walter Reed Army Medical Center of 200 community-based patients aged 65 years or older taking at least 4 chronic medications. The study was conducted from June 2004 to August 2006.\n After a 2-month run-in phase (measurement of baseline adherence, BP, and LDL-C), patients entered a 6-month intervention phase (standardized medication education, regular follow-up by pharmacists, and medications dispensed in time-specific packs). Following the intervention phase, patients were randomized to continued pharmacy care vs usual care for an additional 6 months.\n Primary end point of the observation phase was change in the proportion of pills taken vs baseline; secondary end points were the associated changes in BP and LDL-C. Primary end point of the randomization phase was the between-group comparison of medication persistence.\n A total of 200 elderly patients (77.1% men; mean [SD] age, 78 [8.3] years), taking a mean (SD) of 9 (3) chronic medications were enrolled. Coronary risk factors included drug-treated hypertension in 184 patients (91.5%) and drug-treated hyperlipidemia in 162 (80.6%). Mean (SD) baseline medication adherence was 61.2% (13.5%). After 6 months of intervention, medication adherence increased to 96.9% (5.2%; P<.001) and was associated with significant improvements in systolic BP (133.2 [14.9] to 129.9 [16.0] mm Hg; P = .02) and LDL-C (91.7 [26.1] to 86.8 [23.4] mg/dL; P = .001). Six months after randomization, the persistence of medication adherence decreased to 69.1% (16.4%) among those patients assigned to usual care, whereas it was sustained at 95.5% (7.7%) in pharmacy care (P<.001). This was associated with significant reductions in systolic BP in the pharmacy care group (-6.9 mm Hg; 95% CI, -10.7 to -3.1 mm Hg) vs the usual care group (-1.0 mm Hg; 95% CI, -5.9 to 3.9 mm Hg; P = .04), but no significant between-group differences in LDL-C levels or reductions.\n A pharmacy care program led to increases in medication adherence, medication persistence, and clinically meaningful reductions in BP, whereas discontinuation of the program was associated with decreased medication adherence and persistence.\n clinicaltrials.gov Identifier: NCT00393419",
"Poor adherence to antihypertensive drug regimens is believed to be a major contributor to treatment failure. Electronic monitoring of adherence may improve adherence and allow differentiation between those who are nonadherent and those who are pharmacologically nonresponsive. This study was designed to evaluate the effectiveness of electronic monitoring of adherence in lowering blood pressure (BP) in comparison with usual care.\n A total of 258 patients with high BP despite use of antihypertensive medication were randomly assigned to either continuation of usual care (with adjustment in antihypertensive medication if necessary) or to the introduction of electronic monitoring. Adherence to antihypertensive medication was monitored for 2 months without medication changes. The primary outcome measure was the proportion of patients who reached target BP levels after a 5-month follow-up period.\n At 5 months, 50.6% of the patients in the usual care group reached adequate BP, v 53.7% in the electronic monitoring group (P = .73). The percentages of patients with drug additions or increases in dosage were higher in the usual care group compared with those in whom adherence was monitored (P < .01).\n These data show that electronic monitoring in comparison to usual care results in similar BP control but leads to fewer drug changes and less drug use. This result is likely to be achieved by improving adherence. Hence a strategy that includes electronic monitoring has the potential to prevent unnecessary treatment escalation in patients with poor adherence.",
"To evaluate a pharmacist-conducted educational and monitoring programme, designed to promote dietary and lifestyle modification and compliance with lipid-lowering drug therapy, for patients with dyslipidaemia.\n This was a prospective, randomized, controlled study. The participants were 94 adults, with 81 completing the study (intervention group: 39; control group: 42), with a cardiovascular-related diagnosis and discharged from hospital, between April and October 2001, on lipid-lowering drug therapy. Patients in the intervention group were visited at home monthly by a pharmacist, who educated the patients on the goals of lipid-lowering treatment and the importance of lifestyle issues in dyslipidaemia and compliance with therapy, assessed patients for drug-related problems, and measured total blood cholesterol levels using point-of-care testing. Patients in the control group received standard medical care. The main outcome measure was total blood cholesterol levels after 6 months, and an evaluation of patient and general practitioner satisfaction with the programme.\n There was no significant difference in baseline total blood cholesterol levels between the two groups. The reduction over the course of the study in cholesterol levels within the intervention group was statistically significant (4.9 +/- 0.7 to 4.4 +/- 0.6, P<0.005), whereas there was no change within the control group (P=0.26). At follow-up, 44% of the intervention group patients and 24% of the control group patients had cholesterol levels below 4.0 mmol/L (P=0.06). The reduction in total cholesterol in the intervention group should translate to an expected 21% reduction in cardiovascular mortality risk and a 16% reduction in total mortality risk--more than twice the risk reduction achieved in the control group. In addition, the programme was very well received by the patients and their general practitioners, by satisfaction questionnaire.\n A pharmacist-conducted educational and monitoring intervention improved the outcomes of lipid-lowering drug therapy.",
"Maintaining greater than 95% adherence to antiretroviral medication is necessary in order to have the greatest therapeutic impact on HIV infection. Furthermore, evidence suggests that adherence rates of between 70% and 89% are significantly associated with viral rebound and the development of drug resistance. Adherence rates at and above the 95% level are difficult for patients to achieve and maintain. Our aim was to determine if an adherence intervention could improve adherence among patients attending an ambulatory care clinic at a large public hospital. The intervention was delivered by a multidisciplinary team of health care professionals and consisted of education coupled with the provision of devices designed to assist patient memory and adherence. A crucial component of the intervention consisted of the identification of patient specific barriers to adherence and the development of strategies to circumvent these problems. Adherence was assessed using patient self-report over the past 4, 7, and 28 days and by calculation of the Morisky score. The study was conducted as a randomised controlled trial using the stepped wedge design with a total of 68 subjects randomised to receive the intervention over a 20-week period. Adherence before and after the intervention formed the analysis. There was a significant decrease in the number of missed doses over the past 4 (1.9 to 1.0, p < 0.001), 7 (3.0 to 1.8, p < 0.001) and 28 (7.4 to 4.2, p < 0.001) days and a decrease in the Morisky score, indicating an improvement in medication taking behaviour (1.3 to 0.5 p < 0.001).",
"To determine whether a patient education programme (PE) would improve rates of adherence to a slow acting antirheumatic drug and to assess any subsequent effect on patient outcome.\n A randomly controlled study comprising 100 patients with rheumatoid arthritis (49 control CG; 51 experimental EG) requiring D-penicillamine (DPA). The same practitioner saw patients on seven occasions, for the same length of time. The EG received 7 x 30 minute one to one sessions of PE, while the CG received standard management. The primary measure of adherence was a pharmacological marker (phenobarbitone) encapsulated with the DPA assayed at monthly intervals for six months. Plasma viscosity (PV), C reactive protein, articular index, morning stiffness, and pain score were used to assess outcome.\n 454 blood samples were collected and assayed and the pharmacological marker showed the EG to be significantly more adherent on more occasions than the CG (p<0.05). Patterns of adherence over time showed that at 12 weeks 86% (38/44) of those in the EG compared with 64% (29/45) of the CG remained adherent (p=0.01). These trends continued and by the end of the study 85% (29/34) of the EG compared with 55% (23/42) of the CG were taking their DPA as prescribed. Fifteen patients (12 from the EG) experienced side effects requiring study withdrawal and 14 patients requested study withdrawal (two from the EG). On study entry patients in the CG had significantly higher levels of PV than the EG and this remained so throughout the research. However, on completion, the health status of patients in both groups had improved significantly (p<0.01).\n PE significantly increased adherence to DPA and its effects persisted over a period of six months. No additional clinical benefit was detected in the EG in comparison with the CG.",
"To assess the efficacy of a couple-based intervention to improve medication-taking behavior in a clinic population with demonstrated adherence problems.\n A randomized controlled trial (SMART Couples Study) conducted between August 2000 and January 2004.\n Two HIV/AIDS outpatient clinics in New York City.\n Heterosexual and homosexual HIV-serodiscordant couples (n = 215) in which the HIV-seropositive partner had < 80% adherence at baseline. The sample was predominantly lower-income racial/ethnic minorities.\n Participants were randomly assigned to a four-session couple-focused adherence intervention or usual care. The intervention consisted of education about treatment and adherence, identifying adherence barriers, developing communication and problem-solving strategies, optimizing partner support, and building confidence for optimal adherence.\n Medication adherence at week 8 (2 weeks after the intervention) compared with baseline, assessed with a Medication Event Monitoring System cap.\n Intervention participants showed higher mean medication adherence at post-intervention when compared with controls whether adherence was defined as proportion of prescribed doses taken (76% versus 60%) or doses taken within specified time parameters (58% versus 35%). Also, participants in the intervention arm were significantly more likely to achieve high levels of adherence (> 80%, > 90%, or > 95%) when compared with controls. However, in most cases, effects diminished with time, as seen at follow-up at 3 and 6 months.\n The SMART Couples program significantly improved medication adherence over usual care, although the level of improved adherence, for many participants, was still suboptimal and the effect was attenuated over time.",
"In the treatment of hypertension, problems of nonadherence and consequent poor blood pressure control are particularly severe. Alternative intervention strategies were compared to explore means of improving adherence and lowering blood pressures. In a 3 x 4 repeated measures analysis of variance design, 115 patients were randomly selected and randomly assigned to one of three treatment modalities (routine clinic care, patient education, and contingency contracting) and were followed over four clinic visits. Subjects' knowledge about hypertension and its management, adherence to requests for regular medical follow-up, and blood pressure levels were measured. Patient education was not effective in lowering blood pressures; it produced an untoward outcome, a dropout rate higher than that for patients receiving only routine clinic care. However, contingency contracting was an effective intervention strategy for improving patient knowledge, F (1,59) = 51.32, p less than .0001; adherence to requests for regular medical care, Max L (2) = 25.9, p less than .0001; and decreasing diastolic blood pressures, F (2,49) = 3.39, p less than .05.",
"To analyse the efficacy of health education (HE) through group session with postal back-up in furthering compliance with therapy for Lipaemia.\n Controlled clinical trial, with random distribution.\n Primary care.\n 110 patients with Hypercholesterolaemia, with new diagnoses or not in treatment, in which medical treatment with statins was indicated as a start or change in medication.\n They were distributed in two groups at random, with observation four months after being included in the study and appointments after one, two and four months. 1. Control group (CG): 55 patients who received HE from their family doctor. 2. Intervention group (IG): 55 patients whose HE was monitored: a) a group HE session and b) back-up by letter sent to their homes.\n Patients whose consumption was between 80 and 110% of the amount prescribed were defined as compliant. The pill count was recorded. The percentages of compliant patients and mean compliance (chi squared, Student's t) were analysed. 108 individuals, 41 men and 67 women, completed the trial. There was no difference between the two groups as to age, sex, evolution time, number of diseases and dosage of medicines consumed. 71.3% were compliant (CI, 62.8-79.8%), CG = 61.8% and IG 81.1% (p < 0.05). The mean percentage of compliance was 86.1 +/- 14.3 overall, with CG = 83.8 +/- 14 and IG 88.5 +/- 14 (p = NS).\n The HE intervention with a group session and postal back-up is an effective way of improving therapeutic compliance in cases of hypercholesterolaemia.",
"The objective was to study the effect of \"academic group detailing\" on the prescribing of lipid-lowering drugs in Swedish primary care. A randomized controlled trial was conducted, randomization being by group. Groups of doctors at 134 community health centres were randomly allocated to an intervention and a control group. The 67 intervention health centres were offered four sessions, conducted by a pharmacist, with group information on guidelines for the management of hyperlipidaemia. The number of prescriptions of lipid-lowering drugs per month increased in the intervention health centres and the increase was statistically different from the corresponding change in the control health centres among women in the age group 30-65 years (p = 0.03). The prescription of first-line lipid-lowering drugs increased by 20% in the intervention health centres (p = 0.03). \"Academic group detailing\" by pharmacists to primary care doctors can be an effective method for influencing prescribing practices."
] |
At this stage, reminding patients seems the most promising intervention to increase adherence to lipid lowering drugs. The lack of a gold standard method of measuring adherence is one major barrier in adherence research. More reliable data might be achieved by newer methods of measurement, more consistency in adherence assessment and longer duration of follow up. More recent studies have started using more reliable methods for data collection but follow-up periods remain too short. Increased patient-centredness with emphasis on the patient's perspective and shared decision-making might lead to more conclusive answers when searching for tools to encourage patients to take lipid lowering medication.
|
CD006517
|
[
"14668455",
"19036752"
] |
[
"Comparison of sequential three-drug regimens as initial therapy for HIV-1 infection.",
"High rate of early virological failure with the once-daily tenofovir/lamivudine/nevirapine combination in naive HIV-1-infected patients."
] |
[
"The optimal sequencing of antiretroviral regimens for the treatment of infection with human immunodeficiency virus type 1 (HIV-1) is unknown. We compared several different antiretroviral treatment strategies.\n This multicenter, randomized, partially double-blind trial used a factorial design to compare pairs of sequential three-drug regimens, starting with a regimen including zidovudine and lamivudine or a regimen including didanosine and stavudine in combination with either nelfinavir or efavirenz. The primary end point was the length of time to the failure of the second three-drug regimen.\n A total of 620 subjects who had not previously received antiretroviral therapy were followed for a median of 2.3 years. Starting with a three-drug regimen containing efavirenz combined with zidovudine and lamivudine (but not efavirenz combined with didanosine and stavudine) appeared to delay the failure of the second regimen, as compared with starting with a regimen containing nelfinavir (hazard ratio for failure of the second regimen, 0.71; 95 percent confidence interval, 0.48 to 1.06), as well as to delay the second virologic failure (hazard ratio, 0.56; 95 percent confidence interval, 0.29 to 1.09), and significantly delayed the failure of the first regimen (hazard ratio, 0.39) and the first virologic failure (hazard ratio, 0.34). Starting with zidovudine and lamivudine combined with efavirenz (but not zidovudine and lamivudine combined with nelfinavir) appeared to delay the failure of the second regimen, as compared with starting with didanosine and stavudine (hazard ratio, 0.68), and significantly delayed both the first and the second virologic failures (hazard ratio for the first virologic failure, 0.39; hazard ratio for the second virologic failure, 0.47), as well as the failure of the first regimen (hazard ratio, 0.35). The initial use of zidovudine, lamivudine, and efavirenz resulted in a shorter time to viral suppression.\n The efficacy of antiretroviral drugs depends on how they are combined. The combination of zidovudine, lamivudine, and efavirenz is superior to the other antiretroviral regimens used as initial therapy in this study.\n Copyright 2003 Massachusetts Medical Society",
"The combination of one non-nucleoside reverse transcriptase inhibitor (NNRTI) with two nucleoside reverse transcriptase inhibitors is a validated first-line antiretroviral (ARV) therapy. The once-daily combination of lamivudine, tenofovirDF and nevirapine has not been evaluated in a clinical trial.\n Randomized, open-label, multicentre, non-inferiority trial comparing lamivudine, tenofovirDF and nevirapine once daily (Group 2) with zidovudine/lamivudine and nevirapine twice daily (Group 1), in naive HIV-1-infected patients with a CD4 count <350/mm(3). We planned to enroll 250 patients.\n As of May 2006, 71 patients had been enrolled (35 in Group 1 and 36 in Group 2) and an unplanned interim analysis was done. The groups were comparable at baseline: median CD4 count was 195 and 191/mm(3) and median plasma viral load was 4.9 log(10) and 5.01 log(10), respectively, in Groups 1 and 2. Eight early non-responses (22.2%) were observed, all in Group 2, while two later viral rebounds occurred. Resistance genotypes for the nine Group 2 failing patients showed the mutations M184V/I (n = 3), K65R (n = 6), one or more NNRTI resistance mutations in all cases. At baseline, the nine Group 2 patients who failed had higher median plasma viral load (5.4 log(10)) and lower median CD4 count (110/mm(3)) than the other Group 2 patients (4.7 log(10), P = 0.002 and 223/mm(3), P = 0.004). Nevirapine trough concentrations were not different between the two groups, nor between patients with full viral suppression or those who failed in Group 2. Due to slow recruitment, and those results, the steering committee decided to stop the trial at 12 months.\n In ARV-naive HIV-1-infected patients, the once-daily lamivudine, tenofovirDF and nevirapine regimen resulted in a high rate of early virological failures. The reasons for the failures remain unclear."
] |
There is limited evidence to evaluate second-line therapies in patients with HIV who fail first-line treatment with a WHO-recommended regimen. One randomised trial in 136 patients and two observational studies (both of low quality) suggest no difference in virological suppression whether or not lamivudine is maintained in a second-line regimen. While outcomes of second-line regimens with boosted PIs are favourable in general, there are no studies comparing boosted PIs directly in populations starting second-line regimens. Current recommendations are based on available resources and patient- and public-health-level considerations.
|
CD004002
|
[
"11377600",
"12463616",
"12678188",
"12593490",
"10873185"
] |
[
"Frequency and prevention of symptomless deep-vein thrombosis in long-haul flights: a randomised trial.",
"Prevention of edema, flight microangiopathy and venous thrombosis in long flights with elastic stockings. A randomized trial: The LONFLIT 4 Concorde Edema-SSL Study.",
"The LONFLIT4--Concorde Deep Venous Thrombosis and Edema Study: prevention with travel stockings.",
"The LONFLIT4-Concorde--Sigvaris Traveno Stockings in Long Flights (EcoTraS) Study: a randomized trial.",
"Randomized trial of graded compression stockings for prevention of deep-vein thrombosis after acute stroke."
] |
[
"The true frequency of deep-vein thrombosis (DVT) during long-haul air travel is unknown. We sought to determine the frequency of DVT in the lower limb during long-haul economy-class air travel and the efficacy of graduated elastic compression stockings in its prevention.\n We recruited 89 male and 142 female passengers over 50 years of age with no history of thromboembolic problems. Passengers were randomly allocated to one of two groups: one group wore class-I below-knee graduated elastic compression stockings, the other group did not. All the passengers made journeys lasting more than 8 h per flight (median total duration 24 h), returning to the UK within 6 weeks. Duplex ultrasonography was used to assess the deep veins before and after travel. Blood samples were analysed for two specific common gene mutations, factor V Leiden (FVL) and prothrombin G20210A (PGM), which predispose to venous thromboembolism. Asensitive D-dimer assay was used to screen for the development of recent thrombosis.\n 12/116 passengers (10%; 95% CI 4.8-16.0%) developed symptomless DVT in the calf (five men, seven women). None of these passengers wore elastic compression stockings, and two were heterozygous for FVL. Four further patients who wore elastic compression stockings, had varicose veins and developed superficial thrombophlebitis. One of these passengers was heterozygous for both FVL and PGM. None of the passengers who wore class-I compression stockings developed DVT (95% CI 0-3.2%).\n We conclude that symptomless DVT might occur in up to 10% of long-haul airline travellers. Wearing of elastic compression stockings during long-haul air travel is associated with a reduction in symptomless DVT.",
"The LONFLIT1/2 studies have established that in high-risk subjects after long (> 10 hours) flights the incidence of deep venous thrombosis (DVT) is between 4% and 6%. The LONFLIT4 study has been planned to evaluate the control of edema and DVT in low-medium-risk subjects. The aim of this study was to evaluate edema and its control with specific flight stockings, in long-haul flights. In the first part of the study 400 subjects at low-medium risk for DVT were contacted; 28 were excluded for several nonmedical problems; 372 were randomized into 2 groups to evaluate prophylaxis with stockings in 7-8-hour flights; the control group had no prophylaxis. Below-knee, Scholl, Flight Socks, producing 14-17 mm Hg of pressure at the ankle, were used in the treatment group. The occurrence of DVT was evaluated with high-resolution ultrasound scanning (femoral, popliteal, and tibial veins). Edema was assessed with a composite score based on parametric and nonparametric measurements. Part II: In this part of the study 285 subjects at low-medium risk for DVT were included and randomized into 2 groups to evaluate edema prophylaxis in 11-12-hour flights; the controls had no prophylaxis while the prevention group had below-knee, Scholl, Flight Socks (comparable to part I).\n Part 1: DVT evaluation. Of the 184 included subjects in the stockings group and 188 in the control group, 358 (96.2%) completed the study. Dropouts were due to compliance or connection problems. Age/sex distributions were comparable in the groups. Stockings Group: of 179 subjects (mean age 49; SD 7; M:F = 101:78), none had DVT or superficial thromboses. Control Group: of 179 subjects (mean age 48.4; SD 7.3; M:F = 98:81), 4 (2.2%) had a DVT. There were also 2 superficial thromboses. In total, 3.35% (6) subjects had a thrombotic event. The difference (p<0.002) is significant. Intention-to-treat analysis detects 15 failures in the control group (9 lost + 6 thromboses) out of 188 subjects (7.9%) versus 5 subjects (2.7%) in the stockings group (p <0.05). All thrombotic events were observed in passengers sitting in nonaisle seats. The tolerability of the stockings was very good and there were no complaints or side effects. Thrombotic events were asymptomatic. No difference was observed in the distribution of events between men and women. The 3 women who had a thrombotic event were taking low-dose, oral contraceptives. Edema evaluation: The level of edema at inclusion was comparable in the 2 groups. After the flight there was a score of 6.7 (3.1) in controls; in the stockings group the score was 2.9 times lower (p<0.05). The control of edema with stockings was clear considering both parametric (circumference, volume) and nonparametric (analogue scale lines) data. Part II: DVT evaluation. Of the 285 included subjects, 271 (95%) completed the study. Dropouts were due to low compliance or connection problems. Age/sex distributions were comparable in the groups. Stockings Group: of 142 subjects (mean age 48; SD 8; M:F = 89:53), none had DVT or superficial thromboses. Control Group: of 143 subjects (mean age 47; SD 8; M:F = 87:56), 3 had a popliteal DVT and 3 a superficial thrombosis. In total, 4.2% (6) subjects had a thrombotic event. The difference (p<0.02) between groups is significant. Intention-to-treat analysis detects 14 failures in the control group (8 lost + 6 thromboses = 9.7%) versus 6 (all lost = 4.2% in the stockings group) (p<0.05). Four of 6 events (3 DVT + 1 SVT) were observed in non-aisle seats. The tolerability of the stockings was very good. No difference was observed in the distribution of events between men and women. Edema evaluation: The level of edema at inclusion was comparable in the 2 groups. After the flight there was a score of 8.08 (2.9) in controls while in the stockings group the score was 2.56 (1.5) (p < 0.005). In conclusion. Scholl Flight Socks are very effective in controlling edema. Also this type of compression is effective in significantly reducing the incidence of DVT and thrombotic events in low-medium-risk subjects, in long-haul flights.\n Considering these observations, Flight Socks are effective in controlling edema and in reducing the incidence of DVT in low-medium-risk subjects, in long-haul flights (7-11 hours).",
"The LONFLIT1+2 studies have established that in high risk subjects after long flights (> 10 hours) the incidence of deep venous thrombosis (DVT) is between 4% and 6%. The LONFLIT4 study was designed to evaluate the control of edema and DVT in low-medium risk subjects. The aim of this study was to evaluate edema and its control with specific stockings (ankle pressure between 20 and 30 mm Hg) in long-haul flights. The first part of the study included flights lasting 7-8 hours and the second part included flights lasting 11-12 hours. Ultrasound scans were used to assess thrombosis before and after the flights and a composite edema score was used to evaluate edema and swelling. A group of patients with microangiopathy associated to edema (diabetes, venous hypertension, anti-hypertensive treatment) were also included to evaluate the preventive effects of stockings during flight. Part I: DVT evaluation: Of the 74 subjects in the stocking group and 76 in the control group (150), 144 completed the study. Dropouts were due to low compliance or traveling and connection problems. Age and gender distribution were comparable in the 3 groups as was risk factor distribution. In this part of the study there were no DVTs. Edema Evaluation: The level of edema at inclusion was comparable in the two groups of subjects. After the flight there was an average score of 6.9 (1) in the control group. In the stocking group, the score was on average 2.3 (1), three times lower than in the control group (p < 0.05). Part II: DVT evaluation: Of the 66 included subjects in the stocking group and 68 in the control group (134), 132 completed the study. Dropouts were due to low compliance or connection problems. Age and gender distribution were comparable in the two groups. In the stocking group no DVT was observed. In the control group, 2 subjects had a popliteal DVT and 2 subjects had superficial venous thrombosis (SVT); in total 4 subjects (6%) in the control group had a thrombotic event; the incidence of DVT was 3%. The difference (p < 0.02) is significant.\n The composite edema score at inclusion was comparable in the two groups. After the flight there was a score of 7.94 (2) in the control group, while in the treatment group the score was 3.3 (1.2).\n In all these subjects, the level of edema was very high in the control group and significantly lower in the compression stocking group. Stockings are effective in controlling edema during flights even in subjects with microangiopathy and edema. Compression was well tolerated in normal subjects and in patients.\n The Kendall Travel Socks (Tyco Healthcare, Mansfield, MA, USA) which provide 20-30 mm Hg pressure at the ankle, are effective in controlling edema and reducing the incidence of DVT in both low-medium-risk subjects and in patients with microangiopathy and edema in long-haul flights (7-11 hours).",
"The LONFLIT1/2 studies have established that in high-risk subjects after long ( > 10 hours) flights the incidence of deep venous thrombosis (DVT) may be between 4% and 6%. The LONFLIT4 study was aimed at evaluating the control of edema and DVT prevention in low-medium-risk subjects. In this study prophylaxis of edema with specific travel stockings was evaluated in 2 separate studies involving flights lasting 7 hours and 10-12 hours. Part I. Subjects at low-medium risk for DVT were contacted; 55 subjects were excluded for several nonmedical, travel-related problems or inconvenient evaluation time; the remaining 211 were randomized into 2 groups to evaluate prophylaxis with elastic stockings in 7-8-hour, long-haul flights. The control group had no prophylaxis; the treatment group used below-knee, Sigvaris Traveno elastic stockings (Ganzoni, Switzerland, producing 12-18 mm Hg of pressure at the ankle). Color duplex scanning was used to evaluate the possible presence of DVT; edema/swelling were evaluated with a composite score including the presence of edema (with an edema tester), variations in ankle circumference and leg volumetry, subjective swelling, and discomfort (scale ranging from 0 to 10). Results: Of the 103 included subjects in the stockings group and 108 in the control group (total 211), 195 subjects completed the study. Dropouts (16) were due to low compliance or traveling and connection problems. Age, sex distribution, and risk factors distributions were comparable in the 2 groups. Stockings Group: Of 97 subjects none had DVT or superficial thromboses. Control Group: Of 98 subjects none had thrombosis. The level of edema at inclusion was comparable in the 2 groups of subjects. After flights there was an average score of 6.4 (1.3) in the control group, while in the stockings group the score was on average 2.4 (SD 1), 2.6 times lower than in the control group (p < 0.05). In the control group 83% of the subjects had an evident increase in ankle circumference and volume that was visible at inspection and associated with discomfort. The control of edema with stockings was clear, considering both parametric data (circumference and volume) and nonparametric (analogue scale lines) measurements. Part II. In this part of the study 200 subjects at low-medium risk for DVT were contacted; 35 subjects were excluded for several nonmedical, travel-related problems or inconvenient evaluation time; the remaining 165 were randomized into 2 groups to evaluate prevention in flights lasting between 11 and 12 hours. The control group had no prophylaxis; the treatment group used Traveno stockings. Of the 83 included subjects in the stockings group and 82 in the control group (total 165), 146 subjects completed the study. Dropouts were due to low compliance or connection problems. Age/sex distribution were comparable. Of 75 subjects completing the study in the stockings group and 71 in the control group, none had thrombosis. The average level of edema at inclusion was comparable in the 2 groups (1.1). After the flight there was a score of 8.9 (2) in controls; in the stockings group the score was 2.56 (1.3) (p < 0.05). The control of edema and swelling with stockings even after 11 hours of flight was clear, considering both parametric (circumference, volume) and nonparametric (analogue scale lines) measurements. The tolerability of the stockings was very good and there were no complaints or side effects. In conclusion Sigvaris Traveno stockings are very effective in controlling edema in long-haul flights.",
"Graded compression stockings are commonly used to prevent deep-vein thrombosis (DVT) after stroke, but their efficacy in this setting has not been evaluated. Extrapolation of effectiveness from trials in patients undergoing elective surgery may be inappropriate. We undertook a randomized, controlled trial, with blinded data review, in a University hospital Acute Stroke Unit. Patients were allocated to graded compression stockings or to standard care alone. DVT incidence was determined at baseline and at day 7+/-2 by colour-flow Doppler ultrasound. Ninety-eight patients with acute, immobilizing stroke were randomized; 97 had full outcome data. One patient had clinically manifest DVT, and no patient had pulmonary thromboembolism. DVT was detected in 7/65 patients allocated stockings, and 7/32 controls (odds ratio 0.43, 95% CI 0.14-1.36); DVT involving femoral veins was detected in 3/65 and 2/32. In the first week after stroke, radiologically-detected DVT remains common, but is usually clinically silent. Proximal DVT is less common. Graded compression stockings produced a reduction in DVT incidence comparable to that in other patient groups, but the reduction was not statistically significant, and the magnitude of effect size requires confirmation. There is greater doubt over efficacy in early prevention of proximal DVT."
] |
Airline passengers similar to those in this review can expect a substantial reduction in the incidence of symptomless DVT and leg oedema if they wear compression stockings. We cannot assess the effect of wearing stockings on death, pulmonary embolus or symptomatic DVT because no such events occurred in these trials. Randomized trials to assess these outcomes would need to include a very large number of people.
|
CD006165
|
[
"8621013",
"19488999",
"21088056",
"18397986",
"15386806",
"8077888",
"19008007",
"8745203",
"19123322",
"14679093",
"9126802",
"1523352",
"15307692"
] |
[
"Small doses of subcutaneous insulin as a strategy for preventing slowly progressive beta-cell failure in islet cell antibody-positive patients with clinical features of NIDDM.",
"Protective effects of 1-alpha-hydroxyvitamin D3 on residual beta-cell function in patients with adult-onset latent autoimmune diabetes (LADA).",
"β-cell function and metabolic control in latent autoimmune diabetes in adults with early insulin versus conventional treatment: a 3-year follow-up.",
"Insulin intervention in slowly progressive insulin-dependent (type 1) diabetes mellitus.",
"Rosiglitazone combined with insulin preserves islet beta cell function in adult-onset latent autoimmune diabetes (LADA).",
"A long-term, randomized, comparative study of insulin versus sulfonylurea therapy in type 2 diabetes.",
"Rosiglitazone preserves islet beta-cell function of adult-onset latent autoimmune diabetes in 3 years follow-up study.",
"Insulin versus a combination of insulin and sulfonylurea in the treatment of NIDDM patients with secondary oral failure.",
"[Effect of Tangyikang in improving the function of pancreatic islet beta cells in patients with latent autoimmune diabetes mellitus in adults].",
"Multicenter prevention trial of slowly progressive type 1 diabetes with small dose of insulin (the Tokyo study): preliminary report.",
"Long-term (12 months) treatment with an anti-oxidant drug (silymarin) is effective on hyperinsulinemia, exogenous insulin need and malondialdehyde levels in cirrhotic diabetic patients.",
"Combination daytime chlorpropamide-metformin/bedtime insulin in the treatment of secondary failures in non insulin dependent diabetes.",
"[Study on improvement of islet beta cell function in patients with latent autoimmune diabetes mellitus in adults by integrative Chinese and Western medicine]."
] |
[
"We report a pilot study to determine the preventive effect of small doses of insulin injected subcutaneously on slowly progressive beta-cell damage in islet cell antibody (ICA)-positive patients with apparent NIDDM. Ten NIDDM patients who were ICA' were divided into two groups of five. In the insulin group (age: 51 +/- 8 years [mean +/- SD], sex: 3 men and 2 women), intermediate-type insulin (3-16 U/day) was given once or twice daily as a subcutaneous injection. The sulfonylurea (SU) group (age: 48 +/- 11 years, sex: 3 men and 2 women) was initially treated with a SU agent. Changes in beta-cell function, as indicated by serum C-peptide responses and blood glucose values during a 100-g oral glucose tolerance test, as well as ICA and GAD antibody status, were evaluated for up to 30 months in both groups. ICA status became negative in four of five patients in the insulin group. ICA status did not become negative in any of the patients in the SU group (P = 0.047 vs. insulin group). ICA status was persistently positive in two patients whose beta-cell function eventually progressed to an insulin-dependent state and fluctuated in the remaining three patients. In the insulin group, GAD antibody status became negative in one of four initially GAD antibody-positive NIDDM patients. In the SU group, GAD antibody status was persistently positive in three NIDDM patients (NS vs. insulin group). The serum C-peptide response improved significantly within 6 and 12 months in the insulin group, whereas it decreased progressively in the SU group. The changes in C-peptide response were significantly different between the two groups at 6, 12, 24, and 30 months. Two-hour blood glucose and HbA1 values were unchanged in the insulin group, but they increased in the SU group. Subcutaneous small doses of insulin, resulting in a high rate of negative conversion of ICA and an improved serum C-peptide response, may be effective in treating ICA+ NIDDM patients who are at high risk for slowly progressive beta-cell failure.",
"Previous in vitro and in vivo studies have demonstrated that vitamin D could prevent pancreatic beta-cell destruction and reduce the incidence of autoimmune diabetes. In children with type 1 diabetes, vitamin D treatment produces moderate protective effects on residual beta-cell function and has proven to be safe. Therefore, we hypothesized that vitamin D might have protective effects on beta-cell function in patients with latent autoimmune diabetes in adults (LADA), a form of slowly progressive autoimmune type 1 diabetes.\n Thirty-five patients with LADA were randomly assigned to receive subcutaneous insulin alone (n = 18) or insulin plus 1-alpha-hydroxyvitamin D3 (1-alpha(OH)D3; 0.5 microg per day) (n = 17) for 1 year. Plasma C-peptide levels in fasting state (FCP) and 2 h after 75-g glucose load (PCP) were measured every 6 months with radioimmunoassay.\n Both FCP and PCP levels stayed steady in the insulin plus 1-alpha(OH)D3 group, while FCP decreased in insulin-alone group (P = 0.006) during the 12-month intervention. Seventy percent of patients treated with 1-alpha(OH)D3 maintained or increased their FCP concentrations after 1 year of treatment, while only 22% of patients treated with insulin alone maintained stable FCP levels (P < 0.01). Further analysis on LADA subgroups with different durations of diabetes demonstrated that islet beta-cell function was better preserved (as reflected by significantly higher FCP and PCP levels) in the 1-alpha(OH)D3 plus insulin group only in patients with diabetes duration no longer than 1 year. No severe side effects were observed in any group.\n Our data suggest that 1-alpha(OH)D3 plus insulin therapy can preserve pancreatic beta-cell function in patients with LADA.",
"The optimal treatment of latent autoimmune diabetes in adults (LADA) is not established. We explored whether early insulin treatment, which has shown beneficial effects in rodents and in human pilot studies, would result in better preservation of β-cell function or metabolic control, compared with conventional treatment.\n Glucagon-stimulated C-peptide and HbAlc were evaluated at baseline and after 12, 24 and 36 months in 37 patients recently diagnosed with diabetes, aged ≥ 30 years, non-insulin-requiring and GADAb and/or ICA positive. Twenty patients received early insulin and 17 received conventional treatment (diet ± oral hypoglycaemic agents (OHA), metformin, some and/or sulfonylurea) and insulin when necessary. RESUlts: Level of metabolic control, HbAlc, was preserved in the early insulin treated, while it significantly deteriorated in the conventionally treated. There was no significant difference between the groups in C-peptide after 12, 24 or 36 months, or in the decline of C-peptide. Only baseline C-peptide predicted a C-peptide of ≥ 0.5 nmol/l at 36 months. Gender, body mass index, antibody titres or HbAlc did not influence the levels of C-peptide or HbAlc at baseline or end-of-study, or the decline in C-peptide. Among the diet ± OHA-treated, 5/17 (30%) developed insulin dependency during the follow-up. No major hypoglycaemic events occurred.\n Early insulin treatment in LADA leads to better preservation of metabolic control and was safe. Superior preservation of C-peptide could not be significantly demonstrated. Only baseline level of C-peptide significantly influenced C-peptide level after 3 years. Further studies exploring the best treatment in LADA are warranted.",
"We tested the hypothesis that insulin therapy rather than sulfonylurea (SU) treatment is preferable to reverse or preserve beta-cell function among patients with slowly progressive insulin-dependent (type 1) diabetes (SPIDDM) or latent autoimmune diabetes in adults.\n This multicenter, randomized, nonblinded clinical study screened 4089 non-insulin-dependent diabetic patients for glutamic acid decarboxylase autoantibodies (GADAb). Sixty GADAb-positive non-insulin-requiring diabetic patients with a 5-yr duration or shorter of diabetes were assigned to either the SU group (n = 30) or the insulin group (n = 30). Serum C-peptide responses to annual oral glucose tolerance tests were followed up for a mean of 57 months. The primary endpoint was an insulin-dependent state defined by the sum of serum C-peptide values during the oral glucose tolerance test (SigmaC-peptide) less than 4 ng/ml (1.32 nmol/liter).\n The progression rate to an insulin-dependent state in the insulin group (three of 30, 10%) was lower than that in the SU group (13 of 30, 43%; P = 0.003, log-rank). Longitudinal analysis demonstrated that SigmaC-peptide values were better preserved in the insulin group than in the SU group. Multiple regression analysis demonstrated that insulin treatment, a preserved C-peptide response, and a low GADAb titer at entry were independent factors in preventing progression to an insulin-dependent state. Subgroup analysis suggested that insulin intervention was highly effective for SPIDDM patients with high GADAb titers [> or =10 U/ml (180 World Health Organization U/ml)] and preserved beta-cell function [SigmaC-peptide > or = 10 ng/ml (3.31 nmol/liter)] at entry. No severe hypoglycemic episodes occurred during the study.\n Insulin intervention to preserve beta-cell function is effective and safe for patients with SPIDDM or latent autoimmune diabetes in adults.",
"LADA is thought to result from the chronic autoimmune destruction of the insulin-producing pancreatic beta cells. In addition to antidiabetic effects, the newly developed insulin sensitizer-thiazolidinediones have the potential to increase the insulin content of islet cells by downregulating local inflammation and autoimmune response. Therefore, we hypothesized that LADA patients might benefit from thiazolidinediones treatment.\n LADA patients, with a fasting C-peptide (FCP) of 0.3 nmol/L or more, were enrolled and randomly assigned to receive subcutaneous insulin alone (insulin group, n = 12) or rosiglitazone plus insulin (insulin + RSG group, n = 11) to compare the impacts on islet beta cell function. Plasma glucose, HbA 1c, fasting C-peptide (FCP) and C-peptide after 2 h 75-g glucose load (PCP) were determined every 6 months. GAD-Ab and C-peptide were measured with radioimmune assays. Islet beta cell function was evaluated by PCP and DeltaCP(DeltaCP = PCP-FCP).\n All of the 23 patients have been followed up for 6 months, 17 cases for 12 months and 14 for 18 months. (1) During 6 months' follow-up, there were no significant changes for DeltaCP and PCP levels in both groups. (2) PCP and DeltaCP levels in insulin + RSG group patients stayed steady during the 12 months' observation (P = 0.161 for both PCP and DeltaCP), while in the insulin alone group, both FCP (P = 0.021) and PCP (P = 0.028) levels decreased significantly. Furthermore, PCP (P = 0.004) and DeltaCP(P = 0.015) differences between 12th month and baseline were higher in insulin + RSG group than those in the insulin group. (3) When observed up to 18 months, PCP and DeltaCP levels in insulin + RSG group patients still stayed steady, while PCP and DeltaCP levels decreased more in the insulin alone group.\n This pilot study suggests that rosiglitazone combined with insulin may preserve islet beta cell function in LADA patients.",
"To study the effect of insulin and sulfonylurea (SU) therapy on glycaemic control, insulin resistance and cardiovascular risk factors in type 2 diabetic subjects.\n A prospective, parallel, randomized, controlled, long-term study.\n Outpatient clinic in tertiary referral centre.\n Thirty-six type 2 diabetic subjects treated with diet and SU, aged 44-69 years and a duration of diabetes of between 2 and 14 years.\n Individually adjusted doses of insulin and glibenclamide.\n Glycosylated haemoglobin (HbA1c), insulin resistance (euglycaemic glucose clamp), levels of lipids, lipoproteins and blood pressure.\n Glycaemic control improved during insulin treatment, but deteriorated on SU; HbA1c levels differed significantly between groups after 12 months of therapy (mean +/- SEM 7.9 +/- 0.3 vs. 9.5 +/- 0.4%, P = 0.004). Body mass index increased significantly during insulin treatment (26.4 +/- 0.7 to 27.8 +/- 0.7 kg/m2, P = 0.0001) and 30% of this increase was a result of an increase in lean body mass. The total glucose disposal rate showed a small increase in the insulin group. Levels of triglycerides and apolipoprotein B were significantly reduced during insulin treatment (1.8 +/- 0.2 to 1.5 +/- 0.2 mmol L-1, P = 0.03 and 1.58 +/- 0.1 to 1.40 +/- 0.08 g L-1, P = 0.003), and insulin prevented a reduction in the levels of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-1 and an increase in Lp(a) lipoprotein observed in the SU group. Blood pressure levels did not change during therapy.\n Insulin therapy was superior to SU treatment in achieving good metabolic control. Despite a modest improvement in cardiovascular risk factors in the insulin-treated group, no significant differences were observed between the groups after 1 year's treatment.",
"The newly developed insulin sensitizer-thiazolidinediones have the potential to downregulate inflammation and autoimmune response. The objective of this study was to observe the beneficial effects on beta-cell function in the LADA patients treated with rosiglitazone. 54 LADA patients were assigned to oral hypoglycemic agents group (GAD-Ab<175 U/mL and FCP>0.3 nmol/L) or early insulin administration group (GAD-Ab>or=175 U/mL or GAD-Ab<175 U/mL and FCP<or=0.3 nmol/L). Then, those patients were randomly assigned to receive sulfonylureas (SUs group) or rosiglitazone (RSG group) therapy, or to receive insulin alone (INS group) or rosiglitazone plus insulin (INS+RSG group). Plasma glucose, HbA1c, fasting C-peptide (FCP) and C-peptide after 2h 75-g glucose load (PCP) were determined every 6 months. The levels of PCP and delta CP were higher in RSG group compared with those in SUs group after the 18th month. The PCP level (after the 12th month) and delta CP level (after the 18th month) in INS+/-RSG group were higher than those in INS group. Rosiglitazone combined with insulin wherever or not preserved beta-cell function in LADA patients after 3 years.",
"Comparison of the effectiveness of combined therapy vs. an insulin regimen in NIDDM patients with secondary failure of oral hypoglycemic agents. RESEARCH DESIGN, PATIENTS AND METHODS: 27 NIDDM patients were randomly allocated to Group A (n = 14, insulin) and Group B (n = 13, insulin and sulfonylurea) with crossover after 3 months. After the next 3 months a decision was made about the further treatment according to the metabolic control. The patients were then treated for another year with the more successful regimen. Metabolic control, residual beta-cell secretory capacity, degree of peripheral insulin resistance (clamp) and insulin dose were followed during the whole study.\n (median, interquartile range, in brackets; *, statistically significant difference at P < 0.05): the combined therapy was better than insulin alone in 2/3 of patients. Glycemic control was better (HbA1c at 3 months: Group A = 7.9(1.1)% vs. Group B = 7.0(0.5)%*; HbA1c at 6 months: Group A = 7.4(1.5)% vs. Group B = 8.1(1.5)%. Insulin dose was lower during the combined therapy in the first 3 months: Group A = 0.62(0.18) U/kg body weight vs. Group B = 0.39(0.16) U/kg body weight*. Combined treatment was associated with increased C-peptide excretion both fasting and postprandially. No significant differences in peripheral insulin resistance were noted between the two groups. The combined treatment remained successful even after one year. The two groups of patients with different effective treatment did not differ significantly in any of the observed parameters.\n the combined therapy was more effective than insulin alone. Its favourable effect persisted after treatment for a year. It seems better to start the treatment of the oral failure with combined therapy compared with insulin first and later followed by combined therapy. On the basis of the observed parameters it is impossible to determine in advance which kind of treatment is more suitable for the individual patient.",
"To investigate the effect and mechanism of Tangyikang (TYK) for improving pancreatic islet beta cell function in patients with latent autoimmune diabetes mellitus in adults (LADA).\n Seventy-four LADA patients were randomly assigned to two groups. The 37 patients in the treatment group were treated with TYK decoction (one dose consisted of red ginseng 10 g, milkvetch root 30 g, lilyturf root 15 g, wild weed 10 g, coptis root 15 g, cape-jasmine fruit 10 g, giant knotweed rhizome 10 g, safflower 10 g and moutan bark 10 g) combined with insulin therapy, and the 37 in the control group treated with insulin therapy alone, and the course for all was 3 months. Changes of glycosylated hemoglobin, index of pancreatic islet beta-cell function (delta CP(2h)/delta BS(2h)), serum interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) were observed before and after treatment.\n All the above-mentioned indexes were improved after treatment in both groups, the post-treatment data showed significant difference between groups in delta CP(2h)/delta BS(2h), (0.258 +/- 0.106 vs 0.168 +/- 0.054, higher in the treatment group, t = 4.626, P < 0.01), but with insignificant difference in glycosylated hemoglobin (t = 0.441, P = 0.660). Besides, the dosage of insulin used in the treatment group was less than that in the control group (t = -4.169, P < 0.01); covariance analysis showed, through excluding impact of different dosages insulin used, IL- 4 level was higher (F = 24.217, P < 0.01) and IFN-gamma level was lower (F = 14.198, P < 0.01) in the treatment group than those in the control group.\n TYK could improve the function of islet beta-cell, its possible mechanism is related with the regulation on cell immunity and the correction of T-lymphocyte subsets (Th1/Th2 ratio) imbalance.",
"In 1996, we designed a randomized multicenter study to assess the effects of small doses of insulin on beta cell failure in slowly progressive type 1 diabetes (the Tokyo Study). We report here the preliminary results of this study. Glutamic acid decarboxylase 65 antibody (GADA)-positive patients were randomly divided into 2 groups: one group received insulin (Ins group), the other a sulfonylurea (SU group). Fifty-four patients (24 Ins group, 30 SU group) were analyzed at the end of a 4-year period. All patients underwent a 75 g oral-glucose test (O-GTT) every 6-12 months. The insulin-dependent stage was defined based on an integrated value of serum C-peptide levels on O-GTT ( summation operator CPR; sum of CPR at 0, 30, 60, 90, and 120 min) below 4.0 ng/mL. The summation operator CPR in the SU group decreased progressively from 22.0 +/- 10.6 to 11.3 +/- 7.5 ng/mL over the 48-month period (p < 0.001 vs. baseline). The summation operator CPR in the Ins group was unchanged. Among the SU group, 30% of subjects (9/30) progressed to IDDM, while 8.3% of Ins group subjects (2/24) progressed to IDDM (p = 0.087). With regard to the subjects who had a preserved C-peptide response ( summation operator CPR >/= 10 ng/mL), the proportion of SU group subjects who progressed to IDDM was significantly higher than that of the Ins group (7/28, 25% vs. 0/21, 0%, p = 0.015). Among subjects with a high GADA titer (>/=0 U/mL), 9/14 (64.3%) of the SU group, but only 2/16 (12.5%) of the Ins group, developed IDDM (p = 0.0068). As to those with a high GADA titer and a preserved C-peptide response, SU group subjects progressed to IDDM (7/12, 58.3%) more frequently than Ins group subjects (0/14, 0%) (p = 0.0012). In summary, our results suggest that small doses of insulin effectively prevent beta cell failure in slowly progressive type 1 diabetes. We recommend avoiding SU treatment and instead administering insulin to NIDDM patients with high GADA titer.",
"Several studies have demonstrated that diabetic patients with cirrhosis require insulin treatment because of insulin resistance. As chronic alcoholic liver damage is partly due to the lipoperoxidation of hepatic cell membranes, anti-oxidizing agents may be useful in treating or preventing damage due to free radicals. The aim of this study was to ascertain whether long-term treatment with silymarin is effective in reducing lipoperoxidation and insulin resistance in diabetic patients with cirrhosis.\n A 12-month open, controlled study was conducted in two well-matched groups of insulin-treated diabetics with alcoholic cirrhosis. One group (n=30) received 600 mg silymarin per day plus standard therapy, while the control group (n=30) received standard therapy alone. The efficacy parameters, measured regularly during the study, included fasting blood glucose levels, mean daily blood glucose levels, daily glucosuria levels, glycosylated hemoglobin (HbA1c) and malondialdehyde levels.\n There was a significant decrease (p<0.01) in fasting blood glucose levels, mean daily blood glucose levels, daily glucosuria and HbA1c levels already after 4 months of treatment in the silymarin group. In addition, there was a significant decrease (p<0.01) in fasting insulin levels and mean exogenous insulin requirements in the treated group, while the untreated group showed a significant increase (p<0.05) in fasting insulin levels and a stabilized insulin need. These findings are consistent with the significant decrease (p<0.01) in basal and glucagon-stimulated C-peptide levels in the treated group and the significant increase in both parameters in the control group. Another interesting finding was the significant decrease (p<0.01) in malondialdehyde/levels observed in the treated group.\n These results show that treatment with silymarin may reduce the lipoperoxidation of cell membranes and insulin resistance, significantly decreasing endogenous insulin overproduction and the need for exogenous insulin administration.",
"To determine the effectiveness of the combination therapy with daytime chlorpropamide-metformin and bedtime NPH insulin in the treatment of secondary failures in NIDDM and to study its effects on insulin secretion.\n Non randomized open study with a duration of two months. The patients were followed six months after ending the study. INSTITUTION: Department of Diabetes and Lipid Metabolism. Instituto Nacional de la Nutrición \"Salvador Zubirán\", Mexico City. CHARACTERISTICS OF THE PATIENTS: Nine patients (seven women and two men) were included. All had NIDDM and secondary failure to antidiabetic oral drugs. Their fasting plasma glucose was 14.5 +/- 2 mM/L and their HbA1c 13.37 +/- 2.9%. At the entry and at the end of the study a 5h-OGTT was done with assays of plasma glucose and C-peptide.\n Chlorpropamide (375 mg/day) plus metformin (1200 mg/day) and bedtime insulin (0.1 U/kg/day).\n After two months on combination therapy, fasting plasma glucose and HbA1c levels were remarkably improved (decreases of 7.3 +/- 0.6 and 9.1 +/- 1.02 respectively, p less than 0.002). The insulin dose was small (6.77 +/- 2.09 U/day). Side effects were minimal and infrequent. During the 5h-OGTT, the mean glucose area under the curve also decreased. The insulin secretion did not change but the C-peptide/glucose ratio increased. At the end of the study, the insulin dose was tapered off and stopped when possible. The four patients with the best glycemic control during the study were able to suspend the bedtime insulin and maintain a good control six months after the insulin suspension.\n The combination therapy is useful in the treatment of secondary failures in NIDDM: Its advantages are the very low mean daily insulin dose needed, the low incidence of side effects and, if a HbA1c less than 8.7% is achieved, the restoration of oral antidiabetic drugs efficacy. The very low insulin dose used in this study could be explained by complementary effects of metformin and bedtime insulin on hepatic glucose output and a putative decrease in peripheral resistance attributable both to sulfonylurea and metformin.",
"To study the effect of integrative Chinese and Western medicine (ICWM) on improvement of the islet beta cell function in treating patients with latent autoimmune diabetes mellitus in adults (LADA).\n Eighty-four patients of LADA were randomly divided into 3 groups (20 in A, 33 in B and 31 in C), they were treated respectively with sulfonylurea, insulin and combination of insulin and Chinese medicine. The changes before and after treatment in blood glucose, glycohemoglobin and islet beta cell function were observed.\n After treatment, the damaged islet beta cell function in Group A was not improved, the secrete peak value of C-peptide was still low and delayed in Group A, but in Group B and C, it shifted earlier, suggesting that a certain degree of improvement and recovery of islet beta cell function. The improving effect in Group C was better.\n Chinese herbal medicine had effect in lowering blood glucose and improving islet beta cell function in patients with diabetes mellitus, and showed a synergistic and enhancing action when combined use with insulin. Early treatment of insulin or combination of insulin and Chinese medicine should be applied to patients with LADA."
] |
Two studies show SU leading to earlier insulin dependence and a meta-analysis of four studies with considerable heterogeneity showed poorer metabolic control if SU is prescribed for patients with LADA compared to insulin. One study showed that vitamin D with insulin may protect pancreatic beta cells in LADA. Novel treatments such as GAD65 in certain doses (20 μg) have been suggested to maintain fasting and stimulated C-peptide levels. However, there is no significant evidence for or against other lines of treatment of LADA.
|
CD006830
|
[
"623512"
] |
[
"Cyclobenzaprine hydrochloride effect on skeletal muscle spasm in the lumbar region and neck: two double-blind controlled clinical and laboratory studies."
] |
[
"A new drug, Cyclobenzaprine hydrochloride (Flexeril), was compared with diazepam (Valium) and placebo in double-blind trials for efficacy in treating spasms and pain in the neck and low back. Complex recording methods involving clinical evaluations (graded), patient self-ratings, goniometry, motion analysis by computer, electromyography of controlled motions and detailed statistical analysis were used. Clinical improvement over two weeks was statistically significant in all treatment groups with a statistically significant preference for Cyclobenzaprine hydrochloride. The most striking improvements recorded were in the electromyographic findings, which showed statistically significant changes for the Cyclobenzaprine group. Clinical muscle spasms are not accompanied by increased myoelectric activity; the reverse is true. With improvement, myoelectric activity in back muscles is augmented during prescribed stressful movements as measured by electromyography and computer analysis combined with complex electrogoniometry."
] |
There was insufficient evidence to support the use of cyclobenzaprine in the treatment of MP. We identified only two small studies in which a total of 35 participants were given cyclobenzaprine, and it was not possible to estimate risks for benefits or harms. Further high quality RCTs of cyclobenzaprine for treating MP need to be conducted before firm conclusions on its effectiveness and safety can be made. Experts in this area should elect cut-off points for participants to identify whether a patient has achieved a clinically relevant reduction of pain (primary outcome), so that their results can be combined easily into future versions of this review.
|
CD005050
|
[
"18187561",
"11994246"
] |
[
"Influenza vaccination in secondary prevention from coronary ischaemic events in coronary artery disease: FLUCAD study.",
"Influenza vaccine pilot study in acute coronary syndromes and planned percutaneous coronary interventions: the FLU Vaccination Acute Coronary Syndromes (FLUVACS) Study."
] |
[
"To evaluate the effect of influenza vaccination on the coronary events in patients with confirmed coronary artery disease (CAD).\n Randomized, double-blind, placebo controlled study. We included 658 optimally treated CAD patients; 477 men, mean age 59.9+/-10.3 years. Three hundred and twenty-five patients received the influenza vaccine, and 333 patients placebo. Median follow-up was 298 (interquartile range 263-317) days. Primary endpoint was the cardiovascular death. Its estimated 12-month cumulative event rate was 0.63% in the vaccine vs. 0.76% in controls (HR 1.06 95% CI: 0.15-7.56, P = 0.95). There were two secondary composite endpoints: (i) the MACE (cardiovascular death, myocardial infarction, coronary revascularization) tended to occur less frequently in the vaccine group vs. placebo with the event rate 3.00 and 5.87%, respectively (HR 0.54;95% CI: 0.24-1.21, P = 0.13). (ii) Coronary ischaemic event (MACE or hospitalization for myocardial ischaemia) estimated 12-month event rate was significantly lower in the vaccine group 6.02 vs. 9.97% in controls (HR 0.54; 95% CI: 0.29-0.99, P = 0.047).\n In optimally treated CAD patients influenza vaccination improves the clinical course of CAD and reduces the frequency of coronary ischaemic events. Large-scale studies are warranted to evaluate the effect of influenza vaccination on cardiovascular mortality. (ClinicalTrials.gov: NCT 00371098).",
"Recent reports have detected an increase in the number of patients with acute coronary syndromes during the flu season. In addition, the World Health Organization recommended vaccination against influenza infection for the Southern hemisphere in the winter of 2001. We evaluated the preventive impact of vaccination on subsequent ischemic events in myocardial infarction patients and in subjects undergoing planned percutaneous coronary angioplasty.\n We included 200 myocardial infarction patients admitted in the first 72 hours and 101 planned angioplasty/stent (PCI) patients without unstable coronary artery disease, prior bypass surgery, angioplasty, or tissue necrosis, in a prospective, multicenter log during the winter season. Infarct patients received a standard therapy and were then randomly allocated in a single-blind manner to either a unique intramuscular influenza vaccination or a control group. Similarly, PCI patients were allocated to either vaccination or control groups. Combined end points (death, reinfarction, and rehospitalization for ischemia) were assessed at 6 months' follow-up. The first primary outcome, cardiovascular death, occurred in 2% of the patients in the vaccine group compared with 8% in the control group (relative risk with vaccine as compared with controls, 0.25; 95% CI 0.07 to 0.86; P=0.01). The triple composite end point occurred in 11% of the patients in the vaccine group compared with 23% in controls (P=0.009).\n Influenza vaccination may reduce the risk of death and ischemic events in patients suffering from infarction and those recovering from angioplasty during flu season. This response could be related to a humoral immune response with positive consequences during flu seasons."
] |
Despite the significant effect noted in the studies, we concluded that there are not enough data to evaluate the effect of vaccination on coronary heart disease.
|
CD000096
|
[
"2880214",
"56650",
"451497",
"2436359",
"2310658",
"1189985",
"360495",
"495045",
"10229720"
] |
[
"Double-blind randomised trial of intravenous glycerol in acute stroke.",
"Double-blind trial of glycerol therapy in early stroke.",
"[Treatment with 10% glycerin in acute ischemic cerebral infarct. Doubleblind study].",
"Glycerol and dextran combined in the therapy of acute stroke. A placebo-controlled, double-blind trial with a planned interim analysis.",
"Investigation of intravascular haemolysis during treatment of acute stroke with intravenous glycerol.",
"The effect of glycerol infusion in acute cerebral infarction.",
"Intravenous glycerol in cerebral infarction: a controlled 4-month trial.",
"Association of glycerol to dexamethasone in treatment of stroke patients.",
"Treatment in a combined acute and rehabilitation stroke unit: which aspects are most important?"
] |
[
"The effects of intravenous glycerol in elderly patients with recent onset of acute ischaemic stroke were evaluated in a double-blind randomised controlled trial. 173 patients received either 500 ml of a 10% solution of glycerol in physiological saline or 500 ml of physiological saline administered intravenously over 4 h daily for 6 consecutive days. The number of deaths within the first week was 10 (12%) in the glycerol group versus 26 (30%) in the controls. Subsequent mortality up to 12 months was similar in the two groups and a survival analysis confirmed a beneficial effect of treatment (p less than 0.02). The neurological and functional recovery of survivors, their length of hospital stay, and the proportion able to return to live in their own home were similar in the two groups. The improvement in survival time with glycerol was achieved without serious adverse effects and without an increase in the proportion of survivors with severe residual disability.",
"The effects of intravenous glycerol and intravenous dextrose were compared using a double-blind trial in twenty-seven patients with acute stroke. Administration continued for up to 6 days. A standard scoring system was used for neurological evaluation. There was no difference in mortality or in improvement in neurological score between the two groups.",
"56 patients with acute ischemic cerebral infarction were randomly allocated to intravenous treatment for 6 days with either 500 ml of a 10% glycerol solution or 500 ml of a 5% dextrose solution (placebo). The neurological status of the patients was evaluated by a blinded investigator before the beginning of the treatment, after 2 weeks and again after 6 months. According to the initial degree of neurological deficit, patients were stratified into a mild, intermediate and severe group (using a scoring system). After 2 weeks there was significantly less neurological deficit in the total glycerol-treated group than in the placebo group (2p less than 0.02). This favourable effect of glycerol was even greater in the patients with an initially intermediate degree of neurological deficity (2p less than 0.01). After 6 months there was no difference between the total glycerol-treated and the placebo group. A beneficial effect of glycerol treatment, however, was still demonstrable in the intermediate group (2p less than 0.05). Mortality was not influenced by glycerol treatment. No side effects of the glycerol treatment could be detected. Intravenous administration of 10% glycerol can thus be recommended in patients with acute cerebral infarction.",
"The results of clinical trials investigating various therapies in acute ischemic stroke have been inconsistent. The effect of glycerol therapy and a combination therapy of glycerol and dextran was evaluated in a double-blind, placebo-controlled study. Repeated neurologic examinations (Day 0, Weeks 1, 6, 12, and 24) according to a modified Mathew score were performed on 62 patients. Statistical analysis showed no superiority of either treatment compared with placebo in acute ischemic stroke. A retrospective estimation of the Type II error of the study yielded approximately p = 0.25. A major side effect was hemolysis in 98% of patients treated with glycerol.",
"1. In patients with acute strokes entering a large ongoing randomised double-blind controlled trial of intravenous glycerol therapy, the extent and pathogenesis of any ensuing haemolysis were evaluated using standard clinical investigations and in vitro techniques. 2. Twenty patients received 10% glycerol in saline (500 ml over 4 h on 6 consecutive days) and 15 received corresponding control treatment with saline. 3. Intravascular haemolysis was evident after the first infusion; compared with the controls the glycerol group had i) a greater mean reduction in serum haptoglobin concentration (P less than .05), and ii) a greater proportion exhibiting haemoglobinaemia (P = 0.03). 4. After 6 days of glycerol treatment, the mean reduction in haemoglobin concentration was only 0.8 g more than in controls; this difference being neither clinically nor statistically significant. 5. Glycerol therapy was not associated with haemoglobinuria, renal insufficiency or disseminated intravascular coagulation. 6. Exposure of red blood cells to 1-10% glycerol in vitro did not induce haemolysis per se; on re-exposure to lower concentrations lysis ensued provided a minimum osmotic gradient was present. 7. Whilst taking standard dosage regimes of glycerol, the stroke patients we studied manifested a degree of intravascular haemolysis but its consequences were not clinically significant; lysis probably ensued after venous blood acquiring high glycerol concentrations mixed with blood containing little or no glycerol.",
"Intravenous administration of glycerol has been used in an effort to improve the prognosis for patients with acute cerebral infarction. Fifty patients were treated actively and 56 served as a control group. The neurological status before, during and after treatment for six days was assessed by a score system. The patients were grouped according to the initial score. Those with the highest and lowest scores did not improve from glycerol infusion. However, the treated patients with intermediate scores, where the prognosis is known to be dubious, showed a significant improvement compared to the controls. The mortality was not influenced. No undesirable side-effects from glycerol were registered.",
"A double-blind, randomized trial was performed with 51 patients suffering from focal ischemic lesions in the territory of the middle cerebral artery. Intravenous infusions of 10% glycerol in 0.9% NaCl--5% glucose solutions were administered twice daily for 6 days to 26 patients, and the same amount of NaCl--glucose solutions to 25 controls. Glycerol did not reduce mortality (9 deaths in each group). The functional recovery was assessed by repeated neurological examinations during the 4 month trial. Glycerol significantly improved global performances and motor and sensory functions in patients with moderate disability, but its effect on global performances was transient. The patients with severe disability were not improved at all.",
"A prospective study of 93 acute stroke patients randomly selected by type of antiedema treatment given (hypertonic glicerol infusion plus dexamethasone versus dexamethasone alone) failed to elicit any statistically significant difference between the two treatments on survival rates and quality of survival 7 and 30 days after the stroke.",
"We have previously shown that treatment of acute stroke patients in our stroke unit (SU) compared with treatment in general ward (GWs) improves short- and long-term survival and functional outcome and increases the possibility of earlier discharge to home. The aim of the present study was to identify the differences in treatment between the SU and the GW and to assess which aspects of the SU care which were most responsible for the better outcome.\n Of the 220 patients included in our trial, only 206 were actually treated (SU, 102 patients; GW, 104 patients). For these patients, we identified the differences in the treatment and the consequences of the treatment. We analyzed the factors that we were able to measure and their association with the outcome, discharge to home within 6 weeks.\n Characteristic features in our SU were teamwork, staff education, functional training, and integrated physiotherapy and nursing. Other treatment factors significantly different in the SU from the GW were shorter time to start of the systematic mobilization/training and increased use of oxygen, heparin, intravenous saline solutions, and antipyretics. Consequences of the treatment seem to be less variation in diastolic and systolic blood pressure (BP), avoiding the lowest diastolic BP, and lowering the levels of glucose and temperature in the SU group compared with the GW group. Univariate analyses showed that all these factors except the level of glucose were significantly associated with discharge to home within 6 weeks. In the final multivariate Cox regression model, shorter time to start of the mobilization/training and stabilized diastolic BP were independent factors significantly associated with discharge to home within 6 weeks.\n Shorter time to start of mobilization/training was the most important factor associated with discharge to home, followed by stabilized diastolic BP, indicating that these factors probably were important in the SU treatment. The effects of characteristic features of an SU, such as a specially trained staff, teamwork, and involvement of relatives, were not possible to measure. Such factors might be more important than those actually measured."
] |
This systematic review suggests a favourable effect of glycerol treatment on short term survival in patients with probable or definite ischaemic stroke but the confidence intervals were wide and the magnitude of the treatment effect may be only minimal. Due to the relatively small number of patients, and that the trials were performed in the pre-CT era, the results must be interpreted cautiously. The lack of evidence of benefit in long term survival does not support the routine or selective use of glycerol treatment in patients with acute stroke.
|
CD003435
|
[
"19269254",
"17690310",
"17690311"
] |
[
"Surgical decompression for space-occupying cerebral infarction (the Hemicraniectomy After Middle Cerebral Artery infarction with Life-threatening Edema Trial [HAMLET]): a multicentre, open, randomised trial.",
"Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY): a randomized, controlled trial.",
"Sequential-design, multicenter, randomized, controlled trial of early decompressive craniectomy in malignant middle cerebral artery infarction (DECIMAL Trial)."
] |
[
"Patients with space-occupying hemispheric infarctions have a poor prognosis, with case fatality rates of up to 80%. In a pooled analysis of randomised trials, surgical decompression within 48 h of stroke onset reduced case fatality and improved functional outcome; however, the effect of surgery after longer intervals is unknown. The aim of HAMLET was to assess the effect of decompressive surgery within 4 days of the onset of symptoms in patients with space-occupying hemispheric infarction.\n Patients with space-occupying hemispheric infarction were randomly assigned within 4 days of stroke onset to surgical decompression or best medical treatment. The primary outcome measure was the modified Rankin scale (mRS) score at 1 year, which was dichotomised between good (0-3) and poor (4-6) outcome. Other outcome measures were the dichotomy of mRS score between 4 and 5, case fatality, quality of life, and symptoms of depression. Analysis was by intention to treat. This trial is registered, ISRCTN94237756.\n Between November, 2002, and October, 2007, 64 patients were included; 32 were randomly assigned to surgical decompression and 32 to best medical treatment. Surgical decompression had no effect on the primary outcome measure (absolute risk reduction [ARR] 0%, 95% CI -21 to 21) but did reduce case fatality (ARR 38%, 15 to 60). In a meta-analysis of patients in DECIMAL (DEcompressive Craniectomy In MALignant middle cerebral artery infarction), DESTINY (DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY), and HAMLET who were randomised within 48 h of stroke onset, surgical decompression reduced poor outcome (ARR 16%, -0.1 to 33) and case fatality (ARR 50%, 34 to 66).\n Surgical decompression reduces case fatality and poor outcome in patients with space-occupying infarctions who are treated within 48 h of stroke onset. There is no evidence that this operation improves functional outcome when it is delayed for up to 96 h after stroke onset. The decision to perform the operation should depend on the emphasis patients and relatives attribute to survival and dependency.",
"Decompressive surgery (hemicraniectomy) for life-threatening massive cerebral infarction represents a controversial issue in neurocritical care medicine. We report here the 30-day mortality and 6- and 12-month functional outcomes from the DESTINY trial.\n DESTINY (ISRCTN01258591) is a prospective, multicenter, randomized, controlled, clinical trial based on a sequential design that used mortality after 30 days as the first end point. When this end point was reached, patient enrollment was interrupted as per protocol until recalculation of the projected sample size was performed on the basis of the 6-month outcome (primary end point=modified Rankin Scale score, dichotomized to 0 to 3 versus 4 to 6). All analyses were based on intention to treat.\n A statistically significant reduction in mortality was reached after 32 patients had been included: 15 of 17 (88%) patients randomized to hemicraniectomy versus 7 of 15 (47%) patients randomized to conservative therapy survived after 30 days (P=0.02). After 6 and 12 months, 47% of patients in the surgical arm versus 27% of patients in the conservative treatment arm had a modified Rankin Scale score of 0 to 3 (P=0.23).\n DESTINY showed that hemicraniectomy reduces mortality in large hemispheric stroke. With 32 patients included, the primary end point failed to demonstrate statistical superiority of hemicraniectomy, and the projected sample size was calculated to 188 patients. Despite this failure to meet the primary end point, the steering committee decided to terminate the trial in light of the results of the joint analysis of the 3 European hemicraniectomy trials.",
"There is no effective medical treatment of malignant middle cerebral artery (MCA) infarction. The purpose of this clinical trial was to assess the efficacy of early decompressive craniectomy in patients with malignant MCA infarction.\n We conducted in France a multicenter, randomized trial involving patients between 18 and 55 years of age with malignant MCA infarction to compare functional outcomes with or without decompressive craniectomy. A sequential, single-blind, triangular design was used to compare the rate of development of moderate disability (modified Rankin scale score < or =3) at 6 months' follow-up (primary outcome) between the 2 treatment groups.\n After randomization of 38 patients, the data safety monitoring committee recommended stopping the trial because of slow recruitment and organizing a pooled analysis of individual data from this trial and the 2 other ongoing European trials of decompressive craniectomy in malignant MCA infarction. Among the 38 patients randomized, the proportion of patients with a modified Rankin scale score < or =3 at the 6-month and 1-year follow-up was 25% and 50%, respectively, in the surgery group compared with 5.6% and 22.2%, respectively, in the no-surgery group (P=0.18 and P=0.10, respectively). There was a 52.8% absolute reduction of death after craniectomy compared with medical therapy only (P<0.0001).\n In this trial, early decompressive craniectomy increased by more than half the number of patients with moderate disability and very significantly reduced (by more than half) the mortality rate compared with that after medical therapy."
] |
Surgical decompression lowers the risk of death and death or severe disability defined as mRS > 4 in selected patients 60 years of age or younger with a massive hemispheric infarction and oedema. Optimum criteria for patient selection and for timing of decompressive surgery are yet to be defined. Since survival may be at the expense of substantial disability, surgery should be the treatment of choice only when it can be assumed, based on their preferences, that it is in the best interest of patients. Since all the trials were stopped early, an overestimation of the effect size cannot be excluded.
|
CD004587
|
[
"15464315",
"12900339",
"14744971",
"16286586",
"15723977",
"14769686",
"17584571",
"14724301",
"16160130",
"14550694",
"15054589",
"17680858",
"19112781",
"16971716",
"18489933",
"16154019",
"16670444",
"11075740",
"17498576",
"18261680",
"15737962",
"17540198",
"17950142",
"19755236",
"19758877",
"17442201",
"17589978",
"17616297",
"17932898",
"15485474",
"15585732",
"10476589",
"10732888",
"18946065",
"11818641"
] |
[
"High-dose 7-hexanoyltaxol-eluting stent with polymer sleeves for coronary revascularization: one-year results from the SCORE randomized trial.",
"Randomized study to assess the effectiveness of slow- and moderate-release polymer-based paclitaxel-eluting stents for coronary artery lesions.",
"Inhibition of restenosis with a paclitaxel-eluting, polymer-free coronary stent: the European evaLUation of pacliTaxel Eluting Stent (ELUTES) trial.",
"Clinical efficacy of polymer-based paclitaxel-eluting stents in the treatment of complex, long coronary artery lesions from a multicenter, randomized trial: support for the use of drug-eluting stents in contemporary clinical practice.",
"Maintenance of long-term clinical benefit with sirolimus-eluting coronary stents: three-year results of the RAVEL trial.",
"Analysis of 1-year clinical outcomes in the SIRIUS trial: a randomized trial of a sirolimus-eluting stent versus a standard stent in patients at high risk for coronary restenosis.",
"Sirolimus-eluting stents compared with standard stents in the treatment of patients with primary angioplasty.",
"A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease.",
"Comparison of a polymer-based paclitaxel-eluting stent with a bare metal stent in patients with complex coronary artery disease: a randomized controlled trial.",
"Sirolimus-eluting stents for treatment of patients with long atherosclerotic lesions in small coronary arteries: double-blind, randomised controlled trial (E-SIRIUS).",
"ABT-578-eluting stents. The promising successor of sirolimus- and paclitaxel-eluting stent concepts?",
"Single-center randomized evaluation of paclitaxel-eluting versus conventional stent in acute myocardial infarction (SELECTION).",
"Two year follow-up after primary PCI with a paclitaxel-eluting stent versus a bare-metal stent for acute ST-elevation myocardial infarction (the PASSION trial): a follow-up study.",
"Sirolimus-eluting versus uncoated stents in acute myocardial infarction.",
"Comparison of effectiveness and safety of sirolimus-eluting stents versus bare-metal stents in patients with diabetes mellitus (from the Italian Multicenter Randomized DESSERT Study).",
"Incremental cost-effectiveness of drug-eluting stents compared with a third-generation bare-metal stent in a real-world setting: randomised Basel Stent Kosten Effektivitäts Trial (BASKET).",
"Evaluation of a new polymer-coated paclitaxel-eluting stent for treatment of de novo lesions: six-month clinical and angiographic follow-up results of the APPLAUSE trial.",
"A prospective randomized trial comparing stenting to internal mammary artery grafting for proximal, isolated de novo left anterior coronary artery stenosis: the SIMA trial. Stenting vs Internal Mammary Artery.",
"Randomized trial of Sirolimus-Eluting Stent Versus Bare-Metal Stent in Acute Myocardial Infarction (SESAMI).",
"Sirolimus-eluting stents versus bare-metal stents in patients with ST-segment elevation myocardial infarction: 9-month angiographic and intravascular ultrasound results and 12-month clinical outcome results from the MISSION! Intervention Study.",
"Drug-eluting stents compared with thin-strut bare stents for the reduction of restenosis: a prospective, randomized trial.",
"Randomized comparison of dexamethasone-eluting stents with bare metal stent implantation in patients with acute coronary syndrome: serial angiographic and sonographic analysis.",
"One-year results of the SCORPIUS study: a German multicenter investigation on the effectiveness of sirolimus-eluting stents in diabetic patients.",
"Direct stenting of de novo coronary stenoses with tacrolimus-eluting versus carbon-coated carbostents. The randomized JUPITER II trial.",
"Six-month results of a randomized study to evaluate safety and efficacy of a Biolimus A9 eluting stent with a biodegradable polymer coating.",
"Midterm outcomes of prospective, randomized, single-center study of the Janus tacrolimus-eluting stent for treatment of native coronary artery lesions.",
"Comparison of stent graft, sirolimus stent, and bare metal stent implanted in patients with acute coronary syndrome: clinical and angiographic follow-up.",
"Two-year clinical follow-up after sirolimus-eluting versus bare-metal stent implantation assisted by systematic glycoprotein IIb/IIIa Inhibitor Infusion in patients with myocardial infarction: results from the STRATEGY study.",
"Randomized, double-blind, multicenter study of the polymer-based 17-beta estradiol-eluting stent for treatment of native coronary artery lesions: six-month results of the ETHOS I trial.",
"A randomized trial comparing phosphorylcholine-coated stenting with balloon angioplasty as well as abciximab with placebo for restenosis reduction in small coronary arteries.",
"Sirolimus-eluting vs uncoated stents for prevention of restenosis in small coronary arteries: a randomized trial.",
"Usefulness of platelet glycoprotein IIb/IIIa inhibitors in coronary stenting for reconstruction of complex lesions: procedural and 30 day outcome.",
"Effect of glycoprotein IIb/IIIa receptor blockade with abciximab on clinical and angiographic restenosis rate after the placement of coronary stents following acute myocardial infarction.",
"Cardiovascular outcomes after a change in prescription policy for clopidogrel.",
"Prophylactic abciximab in elective coronary stenting: results of a randomized trial."
] |
[
"The Study to COmpare REstenosis Rate between QueST and QuaDDS-QP2 (SCORE) trial was a multicenter, randomized, open-label trial comparing the safety and performance of 13- and 17-mm QuaDDS stents (n = 126) (Quanam Medical Corp., Santa Clara, California/Boston Scientific Corp., Natick, Massachusetts) versus uncoated control stents (n = 140) in focal, de novo coronary lesions.\n The pioneering drug-delivery QuaDDS stent used four to six acrylate polymer sleeves, each loaded with 800 microg of the paclitaxel derivative 7-hexanoyltaxol.\n Clinical end points were assessed at 1, 6, and 12 months post procedure. Quantitative coronary angiography and intravascular ultrasound were performed post procedure and at six-month follow-up.\n In the QuaDDS group, early stent thrombosis and myocardial infarction (MI) rates were significantly higher, leading to premature cessation of enrollment. For the QuaDDS group, the stent thrombosis rate increased from 3.2% to 10.3% between 1 and 12 months, associated with increased non-Q-wave MI and death rates. The angiographic restenosis rate at six months was reduced from 32.7% (control) to 7.4% (p < 0.0001). However, the primary end point was not met with six-month target vessel revascularization (TVR) rate as well as the composite major adverse cardiac event rates (cardiac death, MI, and TVR) comparable between groups.\n Despite angiographic indications of potential anti-restenotic benefit, increased rates of stent thrombosis, MI, and cardiac death associated with the QuaDDS stent show an unacceptable safety profile.",
"Early clinical studies demonstrated the feasibility of local paclitaxel delivery in reducing restenosis after treatment of de novo coronary lesions in small patient populations.\n We conducted a randomized, double-blind trial of 536 patients at 38 medical centers evaluating slow-release (SR) and moderate-release (MR) formulations of a polymer-based paclitaxel-eluting stent (TAXUS) for revascularization of single, primary lesions in native coronary arteries. Cohort I compared TAXUS-SR with control stents, and Cohort II compared TAXUS-MR with a second control group. The primary end point was 6-month percent in-stent net volume obstruction measured by intravascular ultrasound. Secondary end points were 6-month angiographic restenosis and 6- and 12-month incidence of major adverse cardiac events, a composite of cardiac death, myocardial infarction, and repeat revascularization. At 6 months, percent net volume obstruction within the stent was significantly lower for TAXUS stents (7.9% SR and 7.8% MR) than for respective controls (23.2% and 20.5%; P<0.0001 for both). This corresponded with a reduction in angiographic restenosis from 17.9% to 2.3% in the SR cohort (P<0.0001) and from 20.2% to 4.7% in the MR cohort (P=0.0002). The incidence of major adverse cardiac events at 12 months was significantly lower (P=0.0192) in the TAXUS-SR (10.9%) and TAXUS-MR (9.9%) groups than in controls (22.0% and 21.4%, respectively), predominantly because of a significant reduction in repeat revascularization of the target lesion in TAXUS-treated patients.\n Compared with a bare metal stent, paclitaxel-eluting stents reduced in-stent neointimal formation and restenosis and improved 12-month clinical outcome of patients with single de novo coronary lesions.",
"The use of a stent to deliver a drug may reduce in-stent restenosis. Paclitaxel interrupts the smooth muscle cell cycle by stabilizing microtubules, thereby arresting mitosis.\n On the basis of prior animal studies, the European evaLUation of the pacliTaxel Eluting Stent (ELUTES) pilot clinical trial (n=190) investigated the safety and efficacy of V-Flex Plus coronary stents (Cook Inc) coated with escalating doses of paclitaxel (0.2, 0.7, 1.4, and 2.7 microg/mm2 stent surface area) applied directly to the abluminal surface of the stent in de novo lesions compared with bare stent alone. The primary efficacy end point was angiographic percent diameter stenosis at 6 months. At angiographic follow-up, percent diameter stenosis was 33.9+/-26.7% in controls (n=34) and 14.2+/-16.6% in the 2.7-microg/mm2 group (n=31; P=0.006). Late loss decreased from 0.73+/-0.73 to 0.11+/-0.50 mm (P=0.002). Binary restenosis (> or =50% at follow-up) decreased from 20.6% to 3.2% (P=0.056), with no significant benefit from intermediate paclitaxel doses. Freedom from major adverse cardiac events in the highest (effective) dose group was 92%, 89%, and 86% at 1, 6, and 12 months, respectively (P=NS versus control). No late stent thromboses were seen in any treated group despite clopidogrel treatment for 3 months only.\n Paclitaxel applied directly to the abluminal surface of a bare metal coronary stent, at a dose density of 2.7 microg/mm2, reduced angiographic indicators of in-stent restenosis without short- or medium-term side effects.",
"Intracoronary polymer-based stent delivery of paclitaxel has been shown to be effective in reducing restenosis in simple coronary lesions, but the evidence base for contemporary use in longer, more complex coronary stenoses is lacking.\n TAXUS VI is a prospective, multicenter, double-blind, randomized trial assessing clinical and angiographic outcomes of the TAXUS Moderate Release paclitaxel-eluting stent in the treatment of long, complex coronary artery lesions. Four hundred forty-eight patients at 44 sites were randomized (1:1) between a drug-eluting TAXUS Express2 and an uncoated Express2 control stent. Per protocol, the 9-month follow-up included an angiographic reevaluation in all patients. The primary end point was the rate of target-vessel revascularization 9 months after the study procedure; secondary end points included the rate of target-lesion revascularization and binary restenosis at follow-up. Mean lesion length in the study was 20.6 mm, with a mean stent-covered length of 33.4 mm. Of all lesions, 55.6% were classified as complex lesions (type C of the AHA/ACC classification). At 9 months, target-vessel revascularization was 9.1% in the TAXUS group and 19.4% in the control group (P=0.0027; relative reduction, 53%). Target-lesion revascularization was reduced from 18.9% to 6.8%, respectively (P=0.0001). The incidence of major adverse cardiac events was similar in the 2 groups, 16.4% and 22.5% in TAXUS and control, respectively (P=0.12), including comparable rates for acute myocardial infarction. Binary restenosis in the stented area was reduced from 32.9% in the control group to 9.1% in the TAXUS patients (P<0.0001).\n The finding that the TAXUS Moderate Release stent system is safe and effective in the treatment of long, complex coronary artery lesions provides the evidence base for the more widespread use of drug-eluting stents in contemporary clinical practice.",
"The use of sirolimus-eluting coronary stents has been associated with a nearly complete elimination of restenosis at 6 months and with a very low 1-year incidence of major adverse cardiac events (MACE). This analysis examined whether these beneficial effects persist over the longer term.\n This multicenter trial randomly assigned 238 patients to revascularization of single, de novo, native coronary artery lesions with sirolimus-eluting versus conventional bare-metal stents. Survival free from target lesion revascularization (TLR), target vessel failure (TVF), and MACE up to 3 years of follow-up was compared between the 2 treatment groups. Complete data sets were available in 94.2% of patients treated with sirolimus-eluting stents and in 94.1% of patients randomized to the control group. The cumulative 1-, 2-, and 3-year event-free survival rates were 99.2%, 96.5%, and 93.7% for TLR and 95.8%, 92.3%, and 87.9% for TVF, respectively, in the sirolimus-eluting stent group, versus 75.9%, 75.9%, and 75.0% for TLR and 71.2%, 69.4%, and 67.3% for TVF in the control group (P<0.001 for both comparisons at 3 years). Rates of MACE at 3 years were 15.8% in patients randomly assigned to sirolimus-eluting stents versus 33.1% in patients assigned to bare-metal stents (P=0.002). One patient treated with a sirolimus-eluting stent died of a cardiac cause between 12 and 36 months.\n Treatment of de novo coronary stenosis with sirolimus-eluting stents was associated with a sustained clinical benefit and very low rates of TLR and of other MACE up to 3 years after device implantation.",
"This study evaluated a large group of patients enrolled in a double-blind randomized trial of the sirolimus-eluting stent to document whether the initial clinical improvement seen in previous smaller series is maintained out to 12 months and to study the potential treatment effect in patient subsets known to be at increased risk of restenosis.\n A total of 1058 patients with de novo native coronary stenosis undergoing clinically indicated percutaneous coronary intervention were randomly assigned to sirolimus-eluting stent (533) or control bare stent (525). Procedural success and in-hospital outcomes were excellent and did not differ between the 2 groups. At 9 months, clinical restenosis, defined as target-lesion revascularization, was 4.1% in the sirolimus limb versus 16.6% in the control limb (P<0.001). At 12 months, the absolute difference in target-lesion revascularization continued to increase and was 4.9% versus 20% (P<0.001). There were no differences in death or myocardial infarction rates. In high-risk patient subsets, defined by vessel size, lesion length, and presence of diabetes mellitus, there was a 70% to 80% reduction in clinical restenosis at 1 year.\n Placement of the sirolimus-eluting stent results in continued clinical improvement at 1 year after initial implantation, with significant reduction in clinical restenosis as defined by target-lesion revascularization. Between 9 and 12 months, the absolute reduction of clinical restenosis continues to increase. Even in high-risk subsets of patients, there is a 70% to 80% relative reduction in clinical restenosis at 12 months with this drug-eluting stent.",
"Sirolimus-eluting stents have been shown to decrease restenosis and reintervention as compared with standard stents. We evaluated the use of sirolimus-eluting stents in primary percutaneous coronary intervention for acute myocardial infarction with ST-segment elevation.\n We randomly assigned 120 patients to compare sirolimus-eluting stents with uncoated stents in primary percutaneous coronary intervention for acute myocardial infarction with ST-segment elevation. The primary end point was composite: death from cardiac causes, recurrent myocardial infarction, or target-lesion revascularization after 360 days.\n The rate of the primary end point was 6.7% in the sirolimus-eluting stent and 11% in the bare-metal stent group (relative risk 1.75, 95% CI 0.47-6.57, P = .402). The survival free from target-vessel failure showed a higher trend in the sirolimus-eluting stent group than in the bare-metal stent group (0.0% vs 5.7%, P = .064). There was no significant difference between the 2 groups in the rate of death (5% and 3.6%, respectively; P = .736), reinfarction (1.7% and 1.8%, respectively; P = .940), or stent thrombosis (3.4% and 1.8%, respectively; P = .621).\n Among selected patients with acute myocardial infarction and ST-segment elevation, the use of sirolimus-eluting stents shows a trend to reduce the rate of target-vessel revascularization in comparison with bare-metal stent.",
"Restenosis after coronary stenting necessitates repeated percutaneous or surgical revascularization procedures. The delivery of paclitaxel to the site of vascular injury may reduce the incidence of neointimal hyperplasia and restenosis.\n At 73 U.S. centers, we enrolled 1314 patients who were receiving a stent in a single, previously untreated coronary-artery stenosis (vessel diameter, 2.5 to 3.75 mm; lesion length, 10 to 28 mm) in a prospective, randomized, double-blind study. A total of 652 patients were randomly assigned to receive a bare-metal stent, and 662 to receive an identical-appearing, slow-release, polymer-based, paclitaxel-eluting stent. Angiographic follow-up was prespecified at nine months in 732 patients.\n In terms of base-line characteristics, the two groups were well matched. Diabetes mellitus was present in 24.2 percent of patients; the mean reference-vessel diameter was 2.75 mm, and the mean lesion length was 13.4 mm. A mean of 1.08 stents (length, 21.8 mm) were implanted per patient. The rate of ischemia-driven target-vessel revascularization at nine months was reduced from 12.0 percent with the implantation of a bare-metal stent to 4.7 percent with the implantation of a paclitaxel-eluting stent (relative risk, 0.39; 95 percent confidence interval, 0.26 to 0.59; P<0.001). Target-lesion revascularization was required in 3.0 percent of the group that received a paclitaxel-eluting stent, as compared with 11.3 percent of the group that received a bare-metal stent (relative risk, 0.27; 95 percent confidence interval, 0.16 to 0.43; P<0.001). The rate of angiographic restenosis was reduced from 26.6 percent to 7.9 percent with the paclitaxel-eluting stent (relative risk, 0.30; 95 percent confidence interval, 0.19 to 0.46; P<0.001). The nine-month composite rates of death from cardiac causes or myocardial infarction (4.7 percent and 4.3 percent, respectively) and stent thrombosis (0.6 percent and 0.8 percent, respectively) were similar in the group that received a paclitaxel-eluting stent and the group that received a bare-metal stent.\n As compared with bare-metal stents, the slow-release, polymer-based, paclitaxel-eluting stent is safe and markedly reduces the rates of clinical and angiographic restenosis at nine months.\n Copyright 2004 Massachusetts Medical Society",
"Compared with bare metal stents, drug-eluting stents reduce restenosis in noncomplex lesions. The utility of drug-eluting stents has not been evaluated in more difficult stenoses.\n To investigate the safety and efficacy of the polymer-based, slow-release paclitaxel-eluting stent in a patient population with more complex lesions than previously studied.\n Prospective, placebo-controlled, double-blind, multicenter randomized trial conducted from February 2003 to March 2004 at 66 academic and community-based institutions with 1156 patients who underwent stent implantation in a single coronary artery stenosis (vessel diameter, 2.25-4.0 mm; lesion length, 10-46 mm), including 664 patients (57.4%) with complex or previously unstudied lesions (requiring 2.25-mm, 4.0-mm, and/or multiple stents) and 9-month clinical and angiographic follow-up.\n Patients were randomly assigned to receive 1 or more bare metal stents (n = 579) or identical-appearing paclitaxel-eluting stents (n = 577).\n Ischemia-driven target vessel revascularization at 9 months.\n Baseline characteristics were well matched. Diabetes was present in 31% of patients. The mean (SD) reference vessel diameter was 2.69 (0.57) mm, the reference lesion length was 17.2 (9.2) mm, and 78% of lesions were type B2/C. A mean (SD) of 1.38 (0.58) stents (total mean [SD] length, 28.4 [13.1] mm) were implanted per lesion; 33% of lesions required multiple stents. Stents that were 2.25 mm and 4.0 mm in diameter were used in 18% and 17% of lesions, respectively. Compared with bare metal stents, paclitaxel-eluting stents reduced the 9-month rate of target lesion revascularization from 15.7% to 8.6% (P<.001) and target vessel revascularization from 17.3% to 12.1% (P = .02). Similar rates were observed for cardiac death or myocardial infarction (5.5% for bare metal stent group vs 5.7% for paclitaxel-eluting stent group) and stent thrombosis (0.7% in both groups). Angiographic restenosis was reduced from 33.9% to 18.9% in the entire study cohort (P<.001), including among patients receiving 2.25-mm stents (49.4% vs 31.2%; P = .01), 4.0-mm stents (14.4% vs 3.5%; P = .02), and multiple stents (57.8% vs 27.2%; P<.001).\n Compared with a bare metal stent, implantation of the paclitaxel-eluting stent in a patient population with complex lesions effectively reduces clinical and angiographic restenosis.",
"Sirolimus-eluting stents have been developed to prevent restenosis in the treatment of coronary artery disease. We investigated the risk of restenosis with use of sirolimus-eluting stents compared with bare-metal stents to assess possible differences.\n We enrolled 352 patients in whom one coronary artery required treatment, with diameter 2.5-3.0 mm and lesion length 15-32 mm. We randomly assigned patients sirolimus-eluting stents (n=175) or bare-metal stents (control, n=177). At 8 months we assessed differences in minimum lumen diameter and binary restenosis within the lesion (restenosis of > or =50% diameter, including 5 mm vessel segments proximal and distal to stented segment). Patients were also followed up for 9 months for major adverse cardiac events. Analysis was by intention to treat.\n Stent implantation was successful in 100% of sirolimus-stent patients and 99.4% of controls. The mean diameter of treated coronary arteries was 2.55 mm (SD 0.37) and mean lesion length was 15.0 mm (6.0). Multiple stents were implanted in 170 (48%) patients. At 8 months, minimum lumen diameter was significantly higher with sirolimus-eluting stents than with control stents (2.22 vs 1.33 mm, p<0.0001). The rate of binary restenosis was significantly reduced with sirolimus-eluting stents compared with control stents (5.9 vs 42.3%, p=0.0001). Significantly fewer patients with sirolimus-eluting stents had major adverse cardiac events at 9 months than did controls (8.0 vs 22.6%, p=0.0002), due mainly to a lower need for target-lesion revascularisations (4.0 vs 20.9%, p<0.0001).\n Sirolimus-eluting stents are better than bare-metal stents for treatment of single long atherosclerotic lesions in a coronary vessel smaller than 3 mm in diameter.",
"ABT-578 is a new synthetic analog of rapamycin, designed to inhibit smooth muscle cell proliferation-a key contributor to restenosis-by blocking the function of the mTOR cell cycle regulatory protein. Given these pharmacodynamics, ABT-578 was considered beneficial for intracoronary delivery to arrest the process responsible for neointimal hyperplasia after angioplasty and stenting. Consequently, the ABT-578-eluting ENDEAVOR stent system has been created, representing a potential new alternative for treating patients with coronary heart disease. In order to evaluate safety, feasibility and efficacy of this stent design, the ENDEAVOR clinical program has been started, including three randomized clinical trials. ENDEAVOR I is the first-in-man trial including 100 patients with native de novo coronary lesions. The 4-month follow-up data, recently presented, demonstrated safety and feasibility of this new drug-eluting stent (DES) concept with a 4-month MACE (major adverse cardiac events) rate of 2.0%. In order to evaluate this stent system in a larger patient population as well as more complex lesion subsets, the multicenter study ENDEAVOR II has been started including a total of 1,200 patients. The enrollment of this study was completed in January 2004. The aim of the US multicenter study ENDEAVOR III is a head-to-head comparison of the ENDEAVOR ABT-578-eluting stent system with the already approved sirolimus-eluting Cypher stent in 369 patients. If the results of both pivotal studies ENDEAVOR II and III confirm the efficacy of the ENDEAVOR stent design observed so far, the ENDEAVOR stent will be established as a new and promising contender in the field of DES.",
"To evaluate the superiority of the paclitaxel-eluting stent (PES) in reducing neointimal hyperplasia (NIH) over its corresponding bare metal stent (BMS) during primary percutaneous coronary intervention (PCI).\n Primary PCI with stent implantation is the repercussion strategy of choice for ST-elevation myocardial infarction (STEMI); nonetheless restenosis rate is still high. Drug-eluting stents have been proven to reduce restenosis rate in many settings, but their use during primary PCI is still controversial.\n Consecutive patients with STEMI <12 hours were randomized to receive PES or BMS. The primary end-point was the percentage of the stent volume obstructed by neointimal proliferation (NIH) measured by intravascular ultrasound (IVUS) at a 7-month angiographic follow-up. Secondary end-points were binary restenosis rate and major adverse cardiac events (MACE, i.e., death, nonfatal myocardial infarction, and target lesion revascularization).\n Eighty patients with STEMI were randomized into the PES or BMS group. Patients were well matched for baseline characteristics and the index procedure was always successful. In-hospital and 1-month MACE were 2.5% per group. NIH at 7 months was 4.6% versus 20% (P< 0.01), late lumen loss 0.1 versus 1.01 mm (P = 0.01). MACE were 7.5% versus 42.5% (P = 0.001) with no difference in death and recurrent myocardial infarction rates. Late-acquired incomplete stent apposition (ISA) rate was 5.1% versus 2.7% (P = 0.65). One subacute stent thrombosis was reported in each group.\n PES was superior to its corresponding BMS in reducing NIH in the STEMI setting without any increase in early and long-term clinical adverse events.",
"This follow-up study was performed to assess the long-term effects of paclitaxel-eluting stents (PES) compared with bare-metal stents (BMS) in patients who had undergone a percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI).\n The PASSION trial randomly assigned 619 patients with STEMI to receive either a PES or BMS. The composite endpoint for the follow-up study was the occurrence of the combination of cardiac death, recurrent myocardial infarction, target lesion revascularisation (TLR) or stent thrombosis at two years. A trend towards a lower rate of the composite endpoint was observed in the PES compared to the BMS group (hazard ratio [HR] 0.70; 95% C.I. 0.45-1.09). This was driven by a reduced TLR in favour of PES (HR 0.60; 95% C.I. 0.34-1.09). Angiographically proven stent thrombosis at two years did not differ significantly between groups (2.1% in the PES group versus 1.4%; HR 1.48; 95% C.I. 0.42-5.23).\n PES implantation for STEMI did not significantly improve clinical outcome at two years after the index event, although there was a trend towards a lower rate of target-lesion revascularisation. The rate of stent thrombosis did not differ significantly between groups.",
"Sirolimus-eluting stents reduce rates of restenosis and reintervention, as compared with uncoated stents. Data are limited regarding the safety and efficacy of such stents in primary percutaneous coronary intervention (PCI) for acute myocardial infarction with ST-segment elevation.\n We performed a single-blind, multicenter, prospectively randomized trial to compare sirolimus-eluting stents with uncoated stents in primary PCI for acute myocardial infarction with ST-segment elevation. The trial included 712 patients at 48 medical centers. The primary end point was target-vessel failure at 1 year after the procedure, defined as target-vessel-related death, recurrent myocardial infarction, or target-vessel revascularization. A follow-up angiographic substudy was performed at 8 months among 174 patients from selected centers.\n The rate of the primary end point was significantly lower in the sirolimus-stent group than in the uncoated-stent group (7.3% vs. 14.3%, P=0.004). This reduction was driven by a decrease in the rate of target-vessel revascularization (5.6% and 13.4%, respectively; P<0.001). There was no significant difference between the two groups in the rate of death (2.3% and 2.2%, respectively; P=1.00), reinfarction (1.1% and 1.4%, respectively; P=1.00), or stent thrombosis (3.4% and 3.6%, respectively; P=1.00). The degree of neointimal proliferation, as assessed by the mean (+/-SD) in-stent late luminal loss, was significantly lower in the sirolimus-stent group (0.14+/-0.49 mm, vs. 0.83+/-0.52 mm in the uncoated stent group; P<0.001).\n Among selected patients with acute myocardial infarction, the use of sirolimus-eluting stents significantly reduced the rate of target-vessel revascularization at 1 year. (ClinicalTrials.gov number, NCT00232830 [ClinicalTrials.gov].).\n Copyright 2006 Massachusetts Medical Society.",
"Few studies directly compared drug-eluting stents and bare-metal stents (BMSs) in diabetic patients. DESSERT was an Italian multicenter randomized trial to show the efficacy of sirolimus-eluting stents (SESs) compared with BMSs in de novo lesions of diabetic patients treated with insulin and/or oral antidiabetics for > or =3 months on top of glycoprotein IIb/IIIa inhibitors. The primary end point was in-stent late lumen loss, assessed using centralized quantitative coronary angiography at 8-month follow-up. Centrally adjudicated composite major adverse cardiac events (MACEs) and target-vessel failure (TVF; death, treated vessel-related acute myocardial infarction, and target-vessel revascularization) at 30 days and 9 and 12 months were secondary end points. Seventy-five patients were randomly assigned to an SES (109 lesions), and 75 (109 lesions), to a BMS. The 2 groups were well balanced for clinical, anatomic, and procedural characteristics. In-stent late lumen loss decreased from 0.96 +/- 0.61 mm for BMSs to 0.14 +/- 0.33 for SESs (p <0.001), and in-segment binary restenosis was 38.8% versus 3.6%, respectively (p <0.001). Twelve-month clinical events were significantly lower in the sirolimus group: MACEs 22.1% versus 40% (p = 0.023), target-lesion revascularization 5.9% versus 30% (p <0.001), and TVF 14.7% versus 34.3% (p = 0.008). At multivariate analysis, stent type was confirmed as an independent predictor of in-segment late loss (p <0.001), binary restenosis (p <0.001), 12-month TVF (p = 0.010), and 12-month MACEs (p = 0.037). In conclusion, the randomized DESSERT showed SESs to be safe and effective in decreasing both angiographic parameters of restenosis and incidence of MACEs compared with BMSs in diabetic patients with de novo 1- or 2-vessel coronary stenoses.",
"No prospective trial-based data are available for incremental cost-effectiveness of drug-eluting stents (DES) compared with bare-metal stents (BMS) in unselected patients, as treated in everyday practice.\n The Basel stent cost-effectiveness trial (BASKET) included 826 consecutive patients treated with angioplasty and stenting for 1281 de-novo lesions, irrespective of indication for angioplasty. Patients were randomised to one of two DES (Cypher, n=264; Taxus, n=281) or to a cobalt-chromium-based BMS (Vision, n=281) and followed up for 6 months for occurrence of major adverse cardiac events and costs. Analysis was by intention-to-treat. The primary endpoint was cost-effectiveness after 6 months, with effectiveness defined as reduction of major adverse cardiac events.\n Cardiac death, myocardial infarction, or target vessel revascularisation occurred in 39 of 544 (7.2%) patients with DES and 34 of 280 (12.1%) with BMS (odds ratio 0.56, 95% CI 0.35-0.91; p=0.02), without significant differences between the two DES. Total costs at 6 months were higher with DES (mean 10,544, SD 6849) than with BMS (9639, 9067; p<0.0001); higher stent costs of DES were not compensated for by lower follow-up costs. Incremental cost-effectiveness ratio of DES compared with BMS to avoid one major event was 18,311, and costs per quality-adjusted life-year gained were more than 50 000. Subgroup analyses showed that DES were more cost-effective for elderly patients in specific high-risk groups.\n In a real-world setting, use of DES in all patients is less cost effective than in studies with selected patients. Use of these stents could be restricted to patients in high-risk groups.",
"This trial assesses the safety and efficacy of the PicoElite stent (amg International GmbH, Raesfeld-Erle, Germany), a new paclitaxel-eluting polymer-based stent.\n This is a first-in-man, single-center pilot trial that randomized 30 patients with 35 de novo coronary lesions in a 2:1 proportion to either the paclitaxel-eluting PicoElite stent (PES group: 20 patients with 24 lesions) or the bare metal ArthosPico stent (BMS group: 10 patients with 11 lesions).\n Baseline characteristics were similar in both groups, apart from younger patients in the PES group (mean age 63.5 years vs. 71.7 years in the BMS group; p = 0.032) and shorter lesion length in the PES group (9.56 mm vs. 14.25 mm in the BMS group; p = 0.02). In both groups, there was no difference in the primary endpoint of major adverse cardiac events (MACE) at 30-day follow up. There was a nonsignificant trend towards lower 6-month MACE and target lesion revascularization (TLR) rates in the PES group (10.5% PES vs. 40.0% in the BMS group for both; p = 0.143), and no stent thrombosis in the PES group. At 6-month angiographic follow up, the PES group demonstrated a significantly reduced in-stent binary restenosis rate (5.0% vs. 40.0%; p = 0.031), in-stent late loss (0.47 mm vs. 1.10 mm; p = 0.004), and in-segment late loss (0.72 mm vs. 1.16 mm; p = 0.016) as compared to the BMS group.\n The 6-month results of the APPLAUSE study demonstrate the safety and efficacy of the paclitaxel-eluting PicoElite stent for de novo lesions, with a significant reduction in late loss and a trend towards less TLR compared to a bare metal control.",
"To compare coronary artery bypass grafting (CABG) with percutaneous transluminal coronary angioplasty (PTCA) in patients with proximal, isolated de novo left anterior descending coronary artery disease and left ventricular ejection fraction of 45%.\n In the multicenter Stenting vs Internal Mammary Artery (SIMA) study, patients were randomly assigned to PTCA and stent implantation or to CABG (using the internal mammary artery). The primary clinical composite end point was event-free survival, including death, myocardial infarction, and the need for additional revascularization. Secondary end points were functional class, antianginal treatment, and quality of life. Analyses were by intention to treat.\n Of 123 patients who accepted randomization, 59 underwent CABG, and 62 were treated with stent implantation (2 patients were excluded because of protocol violation). At a mean +/- SD follow-up of 2.4+/-0.9 years, a primary end point had occurred in 19 patients (31%) in the stent group and in 4 (7%) in the CABG group (P<.001). This significant difference in clinical outcome is due to a higher incidence of additional revascularization in the stent group, the incidence of death and myocardial infarction being similar (7% vs 7%, respectively; P=.90). The functional class, need for antianginal drug, and quality-of-life assessment showed no significant differences.\n Both stent implantation and CABG are safe and highly effective treatments to relieve symptoms in patients with isolated, proximal left anterior descending coronary artery stenosis. Both are associated with a low and comparable incidence of death and myocardial infarction. However, similar to PTCA alone, a percutaneous approach using elective stent placement remains hampered by a higher need for repeated intervention because of restenosis.",
"To confirm whether sirolimus-eluting stents (SES) safely reduce the incidence of restenosis in patients with ST-segment elevation acute myocardial infarction compared with bare-metal stents (BMS).\n In the setting of primary angioplasty, stent restenosis occurs in up to 27% of patients. The introduction of drug-eluting stents has drastically reduced the incidence of restenosis in clinically stable patients.\n We conducted a randomized trial of 320 patients with acute ST-segment elevation myocardial infarction assigned to receive SES or BMS. The primary end point was binary restenosis at 1-year angiographic follow-up.\n At 1 year, the incidence of binary restenosis was lower in the SES group than in the BMS group (9.3% vs. 21.3%, respectively; p = 0.032), as were the rates of target lesion revascularization (4.3% vs. 11.2%; p = 0.02), target vessel revascularization (5% vs. 13.1; p = 0.015), major adverse cardiac events (6.8% vs. 16.8%; p = 0.005), and target vessel failure (8.7% vs. 18.7%; p = 0.007). The incidence of angiographically documented stent thrombosis was 1.2% (n = 2) in the SES group and 0.6% (n = 1) in the BMS group.\n In patients with acute myocardial infarction, SES are superior to BMS, reducing the incidence of binary restenosis by 56%, target lesion revascularization by 61%, target vessel revascularization by 62%, adverse cardiac events by 59%, and target vessel failure by 53% at 1 year. (Sirolimus Eluting Stenting in Acute Myocardial Infarction; http://www.clinicaltrials.gov/ct/show/NCT00288210; NCT00288210).",
"Our purpose was to evaluate the efficacy and safety of drug-eluting stents in the setting of primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI).\n There is inconsistent and limited evidence about the efficacy and safety of drug-eluting stents in STEMI patients.\n A single-blind, single-center, randomized study was performed to compare bare-metal stents (BMS) with sirolimus-eluting stents (SES) in 310 STEMI patients. The primary end point was in-segment late luminal loss (LLL) at 9 months. Secondary end points included late stent malapposition (LSM) at 9 months as determined by intravascular ultrasound imaging and clinical events at 12 months.\n In-segment LLL was 0.68 +/- 0.57 mm in the BMS group and 0.12 +/- 0.43 mm in the SES group with a mean difference of 0.56 mm, 95% confidence interval 0.43 to 0.68 mm (p < 0.001). Late stent malapposition at 9 months was present in 12.5% BMS patients and in 37.5% SES patients (p < 0.001). Event-free survival at 12 months was 73.6% in BMS patients and 86.0% in SES patients (p = 0.01). The target-vessel-failure-free survival was 84.7% in the BMS group and 93.0% in the SES group (p = 0.02), mainly because of a higher target lesion revascularization rate in BMS patients (11.3% vs. 3.2%; p = 0.006). Rates of death, myocardial infarction, and stent thrombosis were not different.\n Sirolimus-eluting stent implantation in STEMI patients is associated with a favorable midterm clinical and angiographic outcome compared with treatment with BMS. However, LSM raises concern about the long-term safety of SES in STEMI patients.",
"Drug-eluting stents have considerably reduced restenosis. Their relative merits have been assessed on the basis of comparisons made with control bare stents with thick struts. However, increased strut thickness negatively affects restenosis. No direct comparisons between drug-eluting stents and bare stents with thin struts have been performed. The aim of this study was to evaluate the relative efficacy of sirolimus-eluting stents (Cypher) as compared with that of bare stents with thin struts (BeStent 2).\n A total of 500 patients with coronary artery disease were randomly assigned to receive a Cypher stent or BeStent. The primary endpoint was angiographic restenosis defined as a stenosis diameter > or = 50% at 6-month angiographic follow-up. The secondary endpoint was the need for target vessel revascularization (TVR) during the year following the procedure. Follow-up angiography was performed in 81.8% of the patients. Patients treated with Cypher stents had a lower angiographic restenosis rate [8.3 vs. 25.5%, relative risk, 0.33 (95% confidence interval, 0.19-0.56), P<0.001] and a lower incidence of TVR [7.2 vs. 18.8%, relative risk, 0.38 (0.22-0.66), P<0.001]. For smaller vessels (< 2.8 mm), the angiographic restenosis rates were 7.0% with the Cypher stent and 34.2% with the BeStent (P<0.001). For larger vessels (> or = 2.8 mm), angiographic restenosis rates were 10.0% with the Cypher stent and 13.1% with the BeStent (P=0.52).\n The drug-eluting stent, Cypher, is associated with a significantly lower risk of restenosis compared with the bare thin-strut BeStent. The advantage of the Cypher stent is vastly reduced in large vessels.",
"The aim of this study is to compare the anti-inflammatory effect of the dexamethasone preloaded stent (Dexamet, Abbott, Galway, Ireland) with the bare metal stent (BMS; BiodivYsio, Biocompatibles Cardiovascular LTD, Galway, Ireland) in patients with acute coronary syndrome (ACS) assessed by angiographic (QCA) and intracoronary ultrasound (ICUS).\n One hundred twenty patients with ACS were randomly assigned to revascularization using the Dexamet stent (n = 60) or BMS (n = 60). Serial QCA analysis and ICUS analysis were performed during long-term follow-up (2.9 F; 20 MHz transducer; Volcano Corp, Brussels, Belgium). Power calculations were performed for QCA-derived differences of lumen loss. In addition, statistical analysis was performed (SPSS for Windows 12.0.1). The target lesion revascularization rate was lower in the Dexamet group (10 [16.67%] vs 20 [33.33%] patients; P = .031). The QCA revealed improved lumen restoration in the Dexamet stent group (lumen loss, 0.55 +/- 0.65 vs 1.07 +/- 0.92 mm [P = .001]; loss index, 0.20 +/- 0.23 vs 0.46 +/- 0.42 [P < .001]). The ICUS revealed greater neointimal proliferation in the BMS versus the Dexamet stent group (3.36 +/- 1.03 vs 3.05 +/- 1.38 mm2; P < .001). Death (n = 1) and the number of total occlusions of the stent segment (n = 1) were identical in both groups.\n Dexamet stents, in comparison with the BMS stents, reduced the target lesion revascularization rate in patients with ACS and lead to better lumen restoration during long-term follow-up.",
"This study sought to analyze the effectiveness of drug-eluting stents in a high-risk group of diabetic patients. Previously, this had been analyzed only in substudies of larger trials or in clinical investigations enrolling a small number of patients.\n Drug-eluting stents are highly effective in reducing the rate of in-stent restenosis.\n Two hundred patients with diabetes and de novo coronary artery lesions were enrolled in 16 centers: 98 were randomly assigned to sirolimus-eluting stents (SES) and 102 received bare-metal stents (BMS). The primary end point was in-segment late luminal loss. Major adverse cardiac events (MACE) rate was analyzed at 30 days and 8 and 12 months.\n The extent of in-segment late luminal loss in the SES group was 0.18 mm compared with 0.74 mm in the BMS group. In-segment restenosis was identified on follow-up angiography in 8.8% of the patients in SES and in 42.1% in BMS (p < 0.0001). Target lesion revascularization was performed in 5.3% of the patients in SES and in 21.1% of the patients in BMS (p = 0.002). The SES was effective in the treatment group with oral diabetic medication as well as in the insulin-dependent treatment group (3.6% SES vs. 38.8% BMS). There was no subacute stent thrombosis in the SES group up to 1 year. The MACE rate was not significantly different at 30 days. At 12 months, MACE rate was 14.7% in SES versus 35.8% in BMS.\n The SES is safe and highly effective in patients with diabetes mellitus and coronary artery disease and associated with a significant decrease in the extent of late luminal loss.",
"Aims: Drug-eluting stents are being increasingly used for the treatment of de novo coronary lesions. This trial compared the performance of tacrolimus-eluting stents (TES) with that of equivalent carbon-coated stents (CCS).Methods and results: The JUPITER II trial enrolled 332 patients (mean age = 64 years, 75% men) with de novo coronary stenoses. Patients were randomly assigned to TES versus CCS and underwent repeat coronary angiography at 6 months. The primary study endpoint was in-stent and in-segment late lumen loss (LLL). The main secondary endpoints included binary restenosis, and rates of major adverse clinical events (MACE), including death, myocardial infarction, target lesion revascularisation and stent thrombosis at 1, 6, and 12 months of follow-up. The procedure was successful in 99.4% of patients in both groups. There was no procedural death, 1 cardiac death at 2 months, and 1 acute and 2 subacute CCS thromboses. Angiographic follow-ups were available in 94.4% and 95.1% of patients assigned to TES and CCS, respectively. The mean in-segment and in-stent LLL was 0.42+/-0.46 mm and 0.65+/-0.47 mm, respectively, in the TES, versus 0.48+/-0.52 mm and 0.66+/-0.53 mm, respectively, in the CCS group (ns). The 12-month cumulative MACE rate was 19.5% in the CCS versus 16.1% in the TES group (ns).Conclusions: Both stents showed high safety, with no stent thrombosis in the TES group. No difference was observed in 6-month angiographic results and 12-month MACE rates between TES and CCS.",
"Objectives: The STEALTH (STent Eluting A9 BioLimus Trial in Humans) trial was the first-in-man study to assess the safety and efficacy of the bioabsorbable-polymer-coated Biolimus A9-eluting BioMATRIX-Stent, as compared to a bare metal stent control (S-Stent). Methods: One hundred twenty patients were enrolled in a prospective, 2:1 randomised, double-blind, multi-center clinical study. Patients with single de novo coronary lesions received either a Biolimus-eluting stent (n=80 patients with 82 lesions) or bare metal control stent (n=40 patients with 40 lesions). The primary study endpoint was in-lesion late lumen loss at 6 month follow-up. Results: The six month in-lesion late loss was significantly reduced in the Biolimus-eluting stent group (0.14 +/- 0.45mm) as compared to the control (0.40 +/- 0.41mm) (p=0.004). The in-stent late loss was 0.26 +/- 0.43mm in the Biolimus-eluting stent group vs. 0.74 +/- 0.45mm in the control (p<0.001). The secondary study endpoint of event-free survival at 6-months was similar in both groups (96.3% Biolimus group vs. 97.5% control; p=0.72). There was no significant difference in target lesion revascularizations due to the low binary restenosis rates in both groups (3.9% in Biolimus group vs. 7.7% in control; p=ns). Conclusions: In this first-in-man feasibility trial, the bioabsorbable-polymer-coated Biolimus A9-eluting stent demonstrated superior efficacy in reducing 6-month in-stent and in-lesion late loss and percent diameter stenosis, with clinical safety similar to bare metal control stents.",
"Long-term efficacy and safety of tacrolimus-eluting stent (Janus) for treatment of coronary artery disease in percutaneous coronary interventions (PCI) \"real world\" is uncertain. The aim of this study was to evaluate the efficacy and safety of Janus stent for treating coronary heart disease in PCI daily practice, the safety of 4-month clopidogrel therapy after Janus stent implantation and the feasibility for treating patients with acute myocardial infarction (AMI) for first time.\n From February 20, 2006 to August 26, 2006, a total of 200 patients were enrolled and randomly assigned to receive either Janus stent (n = 100) or bare metal stent (Tecnic Carbostent, n = 100). All patients were administered with clopidogrel for 4 months and aspirin for life long after stenting.\n Baseline clinical and angiographic characteristics were comparable between the two groups. AMI was present in 37% of patients with Janus and 36% with Tecnic Carbostent. At an average of 246-day follow-up, major adverse cardiac events (MACE) was 6% with the Janus stent and 15% with the Tecnic Carbostent (P = 0.038). Primary events included 1 cardiac death, 1 myocardial infarction (MI) due to subacute stent thrombosis and 13 target lesion revascularizations (TLR) due to restenosis in patients with Tecnic Carbostent and 6 TLR due to restenosis in patients with Janus stent. Although all patients had discontinued clopidogrel for an average of 126 days, there was no additional thrombotic event in the two groups.\n Janus stent is efficient in reducing MACE compared with Tecnic Carbostent at an average of 8-month follow-up. Discontinuation of clopidogrel at 4 months after PCI is safe for patients with Janus stent, including AMI patients. Long-term efficacy of Janus stent in reducing restenosis requires further study.",
"To compare polytetrafluoroethylene stent graft (PTFE) with sirolimus and bare metal stents in reducing in-stent restenosis in native coronary vessels in patients with acute coronary syndrome.\n The study included patients who underwent stent implantation in acute coronary syndrome from January 2003 to May 2004. The patients (n=119) were randomized either to stent graft group (n=40), sirolimus eluting stent group (n=39), or bare metal stent group (n=40). The main outcome measure of the study was the incidence restenosis at 6-month. The secondary outcome was 6-month major adverse coronary event rate.\n The incidence of 6-month major adverse coronary events was similar in all three groups (8 events in stent graft, 9 in sirolimus eluting stent, and 16 in bare metal stent group events). The target lesion revascularization was higher in the bare metal stent group (P=0.044). Restenosis rate, at six-month follow-up was higher in the bare metal stent group compared with the stent graft and sirolimus eluting stent groups. The percent diameter stenosis in the follow-up was significantly higher in the bare metal stent group (P=0.005). The late loss was significantly lower in the sirolimus eluting stent group (mean+/-standard deviation, 0.2+/-0.5 mm), compared with the bare metal stent group (0.7+/-0.7 mm, P=0.034). There was a trend of lower late loss in the stent graft group than in the bare metal stent group.\n Three groups of stents implanted in patients with acute coronary syndrome did not differ in the incidence of major adverse cardiac events. Sirolimus-eluting stents had a lower incidence of in-stent restenosis than bare metal stent group. Stent graft implanted in native coronary arteries appears to be safe and efficient in patients with acute coronary syndrome, but a significant reduction in in-stent restenosis was not achieved.",
"We sought to investigate whether the previously reported midterm clinical benefit of planned sirolimus-eluting stent (SES) implantation in patients with ST-segment elevation myocardial infarction (STEMI) was maintained over a 24-month time period. Moreover, the distribution of clinical events in relation to thienopyridine discontinuation was thoroughly investigated.\n No randomized data are currently available on the safety/benefit profile of SES in this subset of patients beyond 12 months.\n Between March 2003 and April 2004, 175 patients with STEMI were randomly allocated to tirofiban infusion followed by SES or abciximab plus bare-metal stent (BMS). Complete follow-up information up to 720 days was available for all patients.\n The cumulative incidence of death, myocardial infarction (MI), or target vessel revascularization (TVR) remained lower in the tirofiban-SES compared with the abciximab-BMS group at 2 years (24.2% vs. 38.6%, respectively; hazard ratio [HR] 0.56 [95% confidence interval (CI) 0.33 to 0.98]; p = 0.038). The composite of death/MI was similar in the tirofiban-SES (16.1%) and the abciximab-BMS groups (20.5%, HR 0.77 [95% CI 0.38 to 1.55]; p = 0.43) while the need for TVR was markedly reduced (9.8% vs. 25.5%, respectively; HR 0.34 [95% CI 0.16 to 0.77]; p = 0.01) in the tirofiban-SES arm. The rate of confirmed, probable, or possible stent thrombosis did not differ in the 2 groups, nor the incidence of death/MI after thienopyridine discontinuation.\n The midterm clinical benefit of planned SES implantation assisted by tirofiban infusion in STEMI patients was mainly carried over after 2 years with no overall excess of late adverse events after thienopyridine discontinuation.",
"The ETHOS I trial was the first in-human experience evaluating the safety and efficacy of two different release formulations of the 17-beta estradiol-eluting R-Stent versus uncoated control stents for the treatment of patients with single de novo native coronary lesions.\n Estrogens were reported to inhibit neointimal proliferation and to accelerate endothelial regeneration after coronary angioplasty and thus could be an ideal compound to deliver on a stent for the purpose of reducing in-stent restenosis.\n Ninety-five patients were randomized to receive a slow-release (n = 32) or the moderate release (n = 31) formulations or the bare metal stent (n = 32). The primary end point was the 6-month percent in-stent volume obstruction by intravascular ultrasound (IVUS).\n Diabetes was present in 29.5% of patients; the mean reference vessel diameter was 2.90 mm; and the mean lesion length was 13.5 mm. Primary endpoint, 6-month percent in-stent volume obstruction by IVUS, did not differ significantly between the 3 groups (31% +/- 14%, 33% +/- 11%, and 31% +/- 14%, P = 0.83). Secondary endpoints also did not differ significantly between the groups including 6-month rates of in-lesion binary angiographic restenosis (13.3%, 14.3%, and 12.5%, P = 0.98), in-stent late loss (0.82 +/- 0.49 mm, 0.86 +/- 0.53 mm, and 0.84 +/- 0.46 mm, P = 0.97), target lesion revascularization (12.5%, 6.9%, and 6.5%, P = 0.64), and major adverse cardiac events (18.8%, 10.3%, and 6.5%, P = 0.31).\n In this first-in-man randomized trial, the 17-beta estradiol-eluting R-Stent, in either slow- or moderate-release formulations, was well-tolerated, but showed no benefit for treatment of coronary lesions when compared to controls.\n (c) 2007 Wiley-Liss, Inc.",
"The objective of this randomized trial was to assess the antirestenotic effects of phosphorylcholine (PC)-coated stents as well as of abciximab in small coronary arteries when compared with percutaneous transluminal coronary angioplasty (PTCA) and placebo respectively.\n Stent coating with PC has been shown to reduce protein absorption and platelet activation which may reduce the risk of restenosis. Furthermore, on the basis of nondedicated studies abciximab is believed to reduce the risk of restenosis after coronary interventions.\n A total of 502 patients with lesions situated in small coronary arteries (vessel diameter </=2.5 mm) were randomly assigned to be treated with either PC-coated stents (n = 253) or PTCA (n = 249) and with either abciximab (n = 251) or placebo (n = 251) with the use of a 2 x 2 factorial design. All patients were pretreated with 600 mg clopidogrel. The primary end-point was the incidence of angiographic restenosis (>/=50% diameter stenosis) at follow-up; death or myocardial infarction, and target vessel revascularization (TVR), were assessed as secondary end-points.\n Angiographic restenosis did not differ between patients treated with PC-coated stents or with PTCA (39.0% vs. 34.2%; P = 0.30) and between patients receiving abciximab or placebo (39.3% vs. 34.3%; P = 0.29). Similarly, the need for TVR at 1-year follow-up did not differ between patients receiving PC-coated stents or PTCA (20.2% vs. 20.5%; P = 0.98) as well as between patients treated with abciximab or placebo (18.7% vs. 21.9%; P = 0.44).\n PC-coated stents and abciximab failed to reduce the incidence of angiographic restenosis after percutaneous coronary intervention of small coronary arteries. These data strengthen the belief that future studies on prevention of restenosis in small coronary arteries should focus on drug-eluting stents.",
"Percutaneous coronary revascularization of small vessels is associated with a high restenosis rate. Sirolimus-eluting stents reduce restenosis in simple and previously untreated lesions of large coronary arteries, but their outcomes in small vessels have not been adequately investigated.\n To determine whether sirolimus-eluting stents are associated with a reduced 8-month rate of angiographic restenosis in comparison with an uncoated stent.\n This was a randomized, multicenter, single-blind, prospective trial performed with 257 patients undergoing percutaneous coronary revascularization for ischemic heart disease, and who had a previously untreated atherosclerotic lesion located in a small segment with a diameter of 2.75 mm or less, in 20 Italian centers between August 2002 and December 2003.\n Patients were randomly assigned to receive a sirolimus-eluting stent (129 patients) or an uncoated stent having an identical architecture and radiographic appearance (128 patients).\n The primary end point was the 8-month binary in-segment restenosis rate; secondary end points included procedural success and the 8-month rate of major adverse cardiac and cerebrovascular events.\n The mean (SD) reference diameter of the treated segment was 2.2 (0.28) mm; the lesion length, 11.84 (6.15) mm. After 8 months, the binary in-segment restenosis rate was 53.1% (60/113) in the patients receiving an uncoated stent and 9.8% (12/123) in those receiving a sirolimus-eluting stent (relative risk [RR], 0.18; 95% confidence interval [CI], 0.10-0.32; P<.001). Fewer patients randomized to sirolimus-eluting stents experienced major adverse cardiac events (12/129 [9.3%] vs 40/128 [31.3%]; RR, 0.30; 95% CI, 0.15-0.55; P<.001) mainly because of a reduction in target lesion revascularization (9/129 [7%] vs 27/128 [21.1%]; RR, 0.33; 95% CI, 0.14-0.70; P = .002) and myocardial infarction (2/129 [1.6%] vs 10/129 [7.8%]; RR, 0.20; 95% CI, 0.01-0.93; P = .04).\n The use of sirolimus-eluting stents to treat atherosclerotic lesions in small coronary arteries reduces restenosis and may also reduce major adverse cardiac events.",
"Intracoronary stent implantation during percutaneous transluminal coronary angioplasty (PTCA) has shown favorable results, reducing acute complications associated with PTCA, such as coronary artery dissection and abrupt or threatened vessel closure. However, treatment of lesions with a complex morphology and diffuse disease, requiring long or multiple coronary stents, is still associated with a poorer outcome. We investigated the hypothesis that abciximab might lead to a different outcome in patients with complex coronary lesions, which require long or multiple stent implantation.\n One hundred and six patients were randomized to receive either a combination of abciximab (bolus and 12 hour infusion) and weight-adjusted low-dose heparin or weight-adjusted heparin alone and followed up to 30 days.\n The procedural success rate was 100% in both groups of patients. In the control group a composite rate of major adverse events such as any death irrespective of cause, Q wave or non-Q wave myocardial infarction, acute or subacute stent thrombosis and urgent revascularization of 15.3% was shown at 30-day follow-up. The use of abciximab reduced the composite adverse event rate to 3.7% (76% absolute reduction, p < 0.05).\n The use of abciximab during high risk stenting is safe and reduces the risk of cardiac events at 30-day follow-up as compared to standard treatment with heparin. A longer follow-up period is warranted to confirm the beneficial effects observed at 30 days with abciximab in this setting.",
"In the Intracoronary Stenting and Antithrombotic Regimen-2 trial (ISAR-2), we sought to investigate the effect of abciximab on angiographic and clinical restenosis after stenting following acute myocardial infarction (AMI). We also intended to assess the impact of abciximab on clinical outcome in this setting.\n It is unclear whether abciximab reduces neointima formation after stenting. Such an effect may be particularly prominent in thrombus-containing lesions.\n Patients undergoing stenting within 48 h after onset of AMI were randomly assigned to receive either standard-dose heparin or abciximab plus reduced-dose heparin. Of 401 patients randomized, 366 without 30-day adverse events were eligible for six-month angiographic follow-up. Scheduled angiography was performed in 80% of these patients.\n By 30 days, the composite clinical end point of death, reinfarction, and target lesion revascularization (TLR) was reached in 5.0% of the abciximab group and in 10.5% of the control group (p = 0.038). At one year, absolute reduction in the composite clinical end point by abciximab was still 5.7% but had lost its statistical significance. Our primary end point, late lumen loss, was 1.26+/-0.85 mm with abciximab and 1.21+/-0.74 mm with standard heparin (p = 0.61), and binary angiographic restenosis rates were 31.1% and 30.6%, respectively (p = 0.92).\n In patients undergoing stenting following AMI, abciximab exerted beneficial effects by substantially reducing the 30-day rate of major adverse cardiac events. During one-year follow-up, there was no additional benefit from a reduction in TLR nor did abciximab reduce angiographic restenosis.",
"Drug-reimbursement policies may have an adverse effect on patient outcomes if they interfere with timely access to efficacious medications for acute medical conditions. Clopidogrel in combination with aspirin is the recommended standard of care for patients receiving coronary stents to prevent thrombosis. We examined the population-level effect of a change by a Canadian provincial government in a pharmacy-benefits program from a prior-authorization policy to a less restrictive, limited-use policy on access to clopidogrel among patients undergoing percutaneous coronary intervention (PCI) with stenting after acute myocardial infarction.\n We conducted a population-based, retrospective, time-series analysis from April 1, 2000, to March 31, 2005, of all patients 65 years of age or older with acute myocardial infarction who underwent PCI with stenting in Ontario, Canada. The primary outcome was the composite rate of death, recurrent acute myocardial infarction, PCI, and coronary-artery bypass grafting at 1 year, with adjustment for sex and age. The secondary outcome was major bleeding.\n The rate of clopidogrel use within 30 days after hospital discharge following myocardial infarction increased from 35% in the prior-authorization period to 88% in the limited-use period. The median time to the first dispensing of a clopidogrel prescription decreased from 9 days in the first period to 0 days in the second period. The 1-year composite cardiovascular outcome significantly decreased from 15% in the prior-authorization group to 11% in the limited-use group (P=0.02). Rates of bleeding in the two groups did not change.\n The removal of a prior-authorization program led to improvement in timely access to clopidogrel for coronary stenting and improved cardiovascular outcomes.\n 2008 Massachusetts Medical Society",
"The use of abciximab (c7E3 Fab; ReoPro , Eli Lilly & Company, Indianapolis, Indiana) during percutaneous coronary intervention (PCI) decreases the incidence of early (30-day) and late (6-month to 1 year) adverse cardiac ischemic events. In a high-risk population, abciximab also reduced the need for target lesion revascularization. PCI of lesions with complex morphology, particularly long lesions, is associated with more complicated outcomes. The use of multiple and/or long intracoronary stents to cover long coronary lesions may lower the incidence of acute or subacute occlusion, but is still limited by a high late restenosis rate. We characterized patients undergoing elective implantation of long or multiple overlapping coronary stents and determined the impact of abciximab administration on clinical and angiographic outcomes.\n In a prospective, single-center randomized trial, a total of 107 patients undergoing elective implantation of long or multiple overlapping coronary stents were randomly assigned to receive either standard-dose heparin (n = 53) or abciximab plus low-dose heparin (n = 54). The use of abciximab was not associated with an increased incidence of bleeding or vascular complications compared to standard heparin regimen (3.7% versus 3.8%, respectively; p = NS). A 68% reduction in composite in-hospital cardiac events (i.e., death, myocardial infarction, urgent revascularization) was observed in the abciximab group (3.7% versus 11.5%, p = 0.1). At 6-month follow-up, a 48% reduction of target lesion revascularization (11% versus 21%; p = 0.1) and a decrease in binary angiographic restenosis were observed for abciximab-treated patients (17% versus 34%; p < 0.05).\n The peri-procedural use of abciximab during implantation of long or multiple overlapping coronary stents is safe and effective, as it does not increase bleeding or vascular complications compared to standard heparin anticoagulation and reduces the incidence of in-hospital adverse cardiac events; moreover, abciximab improves 6-month clinical and angiographic outcomes in such a complex setting."
] |
Drug-eluting stents releasing sirolimus, paclitaxel, dexamethasone and zotarolimus reduce composite cardiac events. However, this reduction is due largely to reductions in repeat revascularisation rates as there is no evidence of a significant effect on rates of death, MI or thrombosis. The increased cost of drug-eluting stents and lack of evidence of their cost-effectiveness means that various health funding agencies are having to limit or regulate their use in relation to price premium.
|
CD000017
|
[
"8219559",
"12183860"
] |
[
"Surgery or balloon angioplasty for peripheral vascular disease: a randomized clinical trial. Principal investigators and their Associates of Veterans Administration Cooperative Study Number 199.",
"Balloon angioplasty versus bypass grafting in the era of coronary stenting."
] |
[
"Surgical revascularization and angioplasty (PTA) are effective therapies for patients with peripheral arterial disease, but there are no data on long-term survival, limb salvage, and hemodynamic status from a randomized study of such patients. A multicenter, prospective trial compared PTA with bypass surgery (BP) in 263 men who had iliac, femoral, or popliteal artery obstruction.\n Lesions in the iliac versus the femoropopliteal artery and rest pain versus claudication were separately randomized to the two treatment interventions. One hundred twenty-six patients underwent BP, 129 patients underwent PTA, and eight patients were not treated for lower extremity ischemia.\n Three operative deaths occurred in the BP group and none in the PTA group. For the entire study, average annual mortality was higher in the BP group, but survival was not significantly different on life-table analysis (P = .08). Primary success favored BP, while limb salvage favored PTA, but differences were not statistically significant (P = .08 and .35, respectively). Patients with iliac disease or claudication fared better, but there was no statistical difference in response to PTA or BP.\n Patients in both treatment groups had prompt and sustained increases in hemodynamics and quality of life. This study of patients randomly assigned to BP or PTA shows no significant difference in outcomes during a median follow-up of 4 years.",
"Patients with multivessel coronary artery disease are candidates for either angioplasty and stenting or coronary artery bypass grafting. A prospective randomized study designed to compare the both methods included only a minority of the eligible patients.\n To compare coronary artery bypass grafting to angioplasty plus stenting in patients with multivessel disease who declined randomization to a multicenter study (the ARTS).\n During 1997-98 we prospectively followed 96 consecutive patients who were eligible according to the ARTS criteria but refused randomization. Of these patients, 50 underwent angioplasty + stenting and 46 underwent coronary bypass surgery. We compared the incidence of major adverse cardiac and cerebral events, chest pain recurrence, quality of life and procedural cost during the first 6 months.\n All procedures were completed successfully without mortality or cerebral events. The rate of Q-wave myocardial infarction was 2% in the AS group vs. 0% in the CABG group (not significant). Minor complications occurred in 7 patients (14%) in the AS group and in 21 patients (45%) in the CABG group (P < 0.01). At 6 months follow-up the incidence of major cardiac and cerebral events was similar in both groups (11% and 4% in the AS and CABG groups respectively, P = NS). Seventeen patients (36%) in the AS group required repeat revascularization compared to only 3 (7%) in the CABG group (P = 0.002). Nevertheless, quality of life was better, hospitalization was shorter and the cost was lower during the first 6 months after angioplasty.\n Angioplasty with stenting compared to coronary bypass surgery in patients with multivessel disease resulted in similar short-term major complications. However, 36% of patients undergoing angioplasty may need further revascularization procedures during the first 6 months."
] |
These limited results suggest that angioplasty may have had a short term benefit, but this may not have been sustained.
|
CD003498
|
[
"16555138",
"12410073"
] |
[
"The gluten-free, casein-free diet in autism: results of a preliminary double blind clinical trial.",
"A randomized, double-blind, placebo-controlled trial of porcine versus synthetic secretin for reducing symptoms of autism."
] |
[
"This study tested the efficacy of a gluten-free and casein-free (GFCF) diet in treating autism using a randomized, double blind repeated measures crossover design. The sample included 15 children aged 2-16 years with autism spectrum disorder. Data on autistic symptoms and urinary peptide levels were collected in the subjects' homes over the 12 weeks that they were on the diet. Group data indicated no statistically significant findings even though several parents reported improvement in their children. Although preliminary, this study demonstrates how a controlled clinical trial of the GFCF diet can be conducted, and suggests directions for future research.",
"To compare the effects of a single dose of biologic and synthetic porcine secretin to placebo on a variety of autism symptoms.\n Eighty-five children with autism without other medical conditions and not taking other psychotropic medications participated (ages between 3 and 12 years, mean IQ = 55). Children were grouped into trios matched by age and communication level and then randomly assigned to one of three treatment groups: biologic secretin (2 CU/kg), synthetic secretin (0.4 microg/kg), and placebo. Measures collected 1 week before and 4 weeks after infusion included autism symptoms, language skills, and problem behaviors, gathered from parents, teachers, and investigators, who were all blind to treatment. Two-factor, repeated-measures analyses of variance (3 treatment levels by 2 repeated measures, pre- and postinfusion) were used to examine efficacy.\n Direct observation measures did not show change over time related to secretin. Parent reports showed an overall reduction of symptom severity for all treatment groups, including the placebo group. One teacher-report measure showed decreases in autism symptoms in the placebo and synthetic secretin groups.\n No evidence that either biologic or synthetic secretin provided amelioration of symptoms beyond placebo was observed. This held true when children with and without gastrointestinal problems were examined separately."
] |
Research has shown of high rates of use of complementary and alternative therapies (CAM) for children with autism including gluten and/or casein exclusion diets. Current evidence for efficacy of these diets is poor. Large scale, good quality randomised controlled trials are needed.
|
CD001302
|
[
"11384805",
"14585874",
"8005278",
"17313946",
"9806261",
"8612863",
"7593499"
] |
[
"Intravenous albumin versus hydroxyethyl starch for the prevention of ovarian hyperstimulation in an in-vitro fertilization programme: a prospective randomized placebo controlled study.",
"Intravenous albumin does not prevent moderate-severe ovarian hyperstimulation syndrome in high-risk IVF patients: a randomized controlled study.",
"Intravenous albumin for the prevention of severe ovarian hyperstimulation syndrome in an in vitro fertilization program: a prospective, randomized, placebo-controlled study.",
"Human albumin does not prevent ovarian hyperstimulation syndrome in assisted reproductive technology program: a prospective randomized placebo-controlled double blind study.",
"Prophylactic intravenous hydroxyethyle starch solution prevents moderate-severe ovarian hyperstimulation in in-vitro fertilization patients: a prospective, randomized, double-blind and placebo-controlled study.",
"Comparison of intravenous albumin and transfer of fresh embryos with cryopreservation of all embryos for subsequent transfer in prevention of ovarian hyperstimulation syndrome.",
"Decreased incidence of severe ovarian hyperstimulation syndrome in high risk in-vitro fertilization patients receiving intravenous albumin: a prospective study."
] |
[
"A prospective randomized placebo controlled clinical trial was carried out on 250 patients (cycles) considered at risk of developing OHSS in an IVF programme. Criteria for inclusion were: estradiol value of more than 3000 pg/ml or the presence of more than 20 follicles on the day of hCG administration. Patients were randomized by using a random table to receive either 20% human albumin 50 ml (n: 82); 6% hydroxyethyl starch (200/0.5) 500 ml (n: 85) or a placebo of 500 ml 0.9% NaCl solution (n: 83) over 30 min during oocyte collection. Groups were similar with respect to patients' age, estradiol levels on hCG day, body mass index, number of oocytes retrieved, number of embryos transferred and pregnancies (P>0.05). There was no severe OHSS in patients who received albumin and HES while four patients who received placebo developed severe OHSS. On the other hand moderate OHSS was encountered in four patients in the albumin group; five patients receiving HES; and 12 patients receiving placebo. There was a statistically significant difference in the incidence of moderate, severe and overall OHSS among groups (P values of <0.05, <0.05, and <0.01, respectively). Both HES and albumin significantly reduced the incidence of moderate, severe and overall incidence of OHSS. It is concluded that hydroxyethyl starch is a cheaper and safer alternative to Human Albumin in OHSS prevention.",
"Intravenous albumin administration has been described for many years as a debatable, but probably useful preventive measure in ovarian hyperstimulation syndrome (OHSS). The present study details the largest randomized controlled trial to date of albumin infusion versus no treatment in IVF patients with a high risk of developing moderate to severe OHSS.\n Between March 1999 and February 2002, women undergoing IVF at the IVI Valencia with >20 retrieved oocytes were included. A total of 988 patients was initially enrolled. Immediately after oocyte retrieval, patients were allocated to two groups based on a computer randomization: the first group received 40 g human albumin; the second group received no treatment. Subjects were weighed and a blood analysis performed immediately after oocyte retrieval and again 7 days later. Women were monitored on an outpatient basis until menstruation, or until fetal heart activity was detected. Twelve subjects were excluded due to follow-up loss, leaving 976 women (377 of them oocyte donors), with 488 in each group.\n No difference was found between the two groups in terms of patient characteristics and outcome. Moderate-severe and severe-only OHSS rates were similar. The incidence of haemoconcentration and liver and renal dysfunction at 7 days after oocyte retrieval was similar in the two groups. In women who developed moderate/severe (n = 66) or only severe (n = 46) OHSS, there was no difference based on prior albumin administration between blood parameters or body weight on the day of oocyte retrieval, 7 days later, and even when comparing variation between both measurements. Moreover, the number of patients with paracentesis, hospital admissions, complications and days of OHSS until resolution did not differ.\n Albumin infusion on the day of oocyte retrieval is not a useful means of preventing the development of moderate-severe OHSS.",
"To evaluate the efficacy of i.v. administration of human albumin solution for the prevention of severe ovarian hyperstimulation syndrome (OHSS).\n A prospective, randomized, placebo-controlled study comparing the effects of i.v. administration of human albumin solution versus sodium chloride 0.9% solution at the time of oocyte retrieval with patients undergoing IVF-ET who are at high risk for the development of severe OHSS.\n Specialized assisted reproduction unit.\n Thirty-one patients undergoing IVF-ET who had serum E2 levels of 1,906 pg/mL (> 7,000 pmol/L) and multiple follicular development on the day of hCG administration.\n After hCG administration, patients were randomized to receive i.v., either 50 g of human albumin diluted in 500 mL of sodium chloride 0.9% or 500 mL of sodium chloride 0.9% at the time of oocyte retrieval.\n Ovarian size as measured by pelvic ultrasonography, development of ascites, serum E2 concentrations during the luteal phase, and results of the IVF-ET cycles.\n Although no patient who had received human albumin solution developed severe OHSS, there were four such cases in the control group. All four were hospitalized with marked ascites and ovarian enlargement. There were no significant differences between the two groups comparing serum E2 levels on the day of hCG administration and during the luteal phase, the number of oocytes retrieved, fertilization, and pregnancy rates.\n Our preliminary results suggest that the administration of human albumin solution may help to prevent the development of severe OHSS in high-risk patients. Further research is needed to assess the potential of this novel approach.",
"We aimed to clarify the efficiency of IV human albumin in the prevention of ovarian hyperstimulation syndrome (OHSS). We found that human albumin at the described strength does not seem to either prevent or reduce the incidence of severe OHSS in high risk patients undergoing intracytoplasmic sperm injection (ICSI).",
"A prospective, randomized, double-blind and placebo-controlled study was conducted to assess the effectiveness of i.v. administration of 6% hydroxyethyle starch solution (HES) in preventing moderate and severe ovarian hyperstimulation syndrome (OHSS) in patients in an in-vitro fertilization programme. A total of 101 women who had serum oestradiol concentrations >1500 pg/ml and/or more than 10 follicles on day of human chorionic gonadotrophin (HCG) administration were recruited into two groups: HES group (n = 51) received 1000 ml 6% HES; and the placebo group (n = 50) received 1000 ml of sodium chloride 0.9% solution at the time shortly after embryo transfer. Follow-up examinations 7 +/- 1 and 14 +/- 1 days after embryo transfer included transvaginal ultrasound (diameters of each ovary and maximum cysts, number of cysts, ascites), blood tests (serum oestradiol, progesterone, beta-HCG, C-reactive protein, blood count, plasma proteins, electrolytes, kidney function tests) and evaluation of abdominal pain, nausea, diarrhoea, abdominal swelling and weight gain. Only one moderate OHSS developed in the HES group whereas seven moderate-severe cases were observed in the placebo group (P = 0.031). Furthermore, serum oestradiol concentration, leukocyte count, increase in abdominal circumference and weight gain 14 days after embryo transfer were significantly higher in the placebo group. There were no differences between the two groups in terms of age, oestradiol concentration and number of follicles at time of HCG injection. Administration of 6% HES prevents the development of moderate-severe OHSS in risk patients.",
"To compare the efficacy of administration i.v. albumin to prevent severe ovarian hyperstimulation syndrome (OHSS) in patients undergoing ovarian stimulation for IVF with a standard policy of cryopreserving all embryos and to assess the impact of the two methods of treatment on pregnancy rates (PRs).\n Prospective randomized study.\n A tertiary referral center for assisted conception.\n Twenty-six patients undergoing IVF treatment cycles who were considered to be at high risk of developing severe OHSS on the basis of their serum E2 concentrations on the day of hCG administration and the number of oocytes collected.\n In group 1 (n = 13) all the generated embryos were cryopreserved to be transferred subsequently in hormonally manipulated cycles. In group 2 (n = 13) patients received IV infusions of albumin on the day of oocyte retrieval and 5 days later. Patients in group 2 had transfers of fresh embryos.\n The total dosage of hMG used, total number of follicles developed, number of follicles > 14 mm in diameter, serum E2 concentrations and endometrial thickness on day of hCG administration, number of oocytes retrieved, number and quality of embryos generated, PRs per cycle commenced, and onset and degree of any OHSS developed.\n There were no significant differences in the above parameters between the two groups, except for PRs that were significantly higher in patients who had all embryos cryopreserved (38.6% versus 0%).\n The policy of cryopreserving all generated embryos appears as effective as the administration of i.v. albumin in preventing OHSS in high-risk patients and produces significantly higher PRs.",
"The administration of human serum albumin has been reported to prevent severe ovarian hyperstimulation syndrome (OHSS) while undergoing ovarian stimulation protocols for in-vitro fertilization (IVF). This prospective, randomized study investigated the effectiveness of a single dose of human serum albumin (20 g) administered i.v. immediately after oocyte retrieval. Women enrolled in the IVF programme were treated with long gonadotrophin-releasing hormone agonist, triptorelin, and an individually-adjusted human menopausal gonadotrophin protocol. The criteria for inclusion in the study were young age, non-obesity, oestradiol concentration > 9200 pmol/l on the day of human chorionic gonadotrophin administration and > 20 follicles > 14 mm diameter as observed by transvaginal sonography. The treatment group (n = 22) received albumin while the control group (n = 18) did not. Patients were followed-up using ultrasound every 3 days. There was a significantly higher number of severe OHSS cases in the control group (n = 4) than in the treatment group (n = 0) (P = 0.035). Where the data base was restricted to patients with an oestradiol concentration > 15,000 pmol/l, the difference between control and treatment groups was highly significant (P = 0.008). These findings support the use of i.v. albumin in preventing severe OHSS during IVF treatment."
] |
There is limited evidence of benefit from intra-venous albumin administration at the time of oocyte retrieval in the prevention or reduction of the incidence of severe OHSS in high risk women undergoing IVF or ICSI treatment cycles. Hydroxyethyl starch markedly decreases the incidence of severe OHSS.
|
CD008096
|
[
"19032398",
"7555937",
"1298056",
"16708735",
"12796072",
"10768245",
"16440428"
] |
[
"Randomized study of percutaneous endoscopic gastrostomy versus nasogastric tubes for enteral feeding in head and neck cancer patients treated with (chemo)radiation.",
"Percutaneous endoscopic gastrostomy (PEG): comparison of push and pull methods and evaluation of antibiotic prophylaxis.",
"Feeding via nasogastric tube or percutaneous endoscopic gastrostomy. A comparison.",
"A prospective comparison of percutaneous endoscopic gastrostomy and nasogastric tube feeding in patients with acute dysphagic stroke.",
"Percutaneous endoscopic gastrostomy does not prolong survival in patients with dementia.",
"Antibiotic prophylaxis in percutaneous endoscopic gastrostomy (PEG)--results from a prospective randomized multicenter trial.",
"Effect of percutaneous endoscopic gastrostomy on gastro-esophageal reflux in mechanically-ventilated patients."
] |
[
"Percutaneous endoscopic gastrostomy (PEG) tubes have largely replaced nasogastric tubes (NGT) for nutritional support of patients with head and neck cancer undergoing curative (chemo)radiotherapy without any good scientific basis. A randomized trial was conducted to compare PEG tubes and NGT in terms of nutritional outcomes, complications, patient satisfaction and cost. The study was closed early because of poor accrual, predominantly due to patients' reluctance to be randomized. There were 33 patients eligible for analysis. Nutritional support with both tubes was good. There were no significant differences in overall complication rates, chest infection rates or in patients' assessment of their overall quality of life. The cost of a PEG tube was 10 times that of an NGT. The duration of use of PEG tubes was significantly longer, a median 139 days compared with a median 66 days for NGT. We found no evidence to support the routine use of PEG tubes over NGT in this patient group.",
"Infection of the gastrostomy opening after placement of a percutaneous endoscopic gastrostomy (PEG) catheter has been reported to occur quite often, especially when the pull method is used. We therefore compared complications occurring with the pull and push methods, and evaluated the role of antibiotic prophylaxis.\n In a prospective study, 100 consecutive patients were randomly assigned to group A (pull plus antibiotic prophylaxis: amoxycillin-clavulanic acid 3 x 1.2 g i.v. over 24 hours; 37 patients), group B (pull without antibiotic prophylaxis; 34 patients) and group C (push without antibiotic prophylaxis; 29 patients). The indications for PEG placement were dysphagia due to oropharyngeal tumors (56%), neurological disease (32%), or other (12%). Patients were evaluated twice weekly for one month after the PEG placement.\n PEG catheters were successfully placed in 96% of the patients. The total procedure-related complication rate was significantly lower in group A than in groups B and C (28%, 58%, and 70%, respectively; p < 0.01). Major complications occurred in one patient in group A (seeding metastasis of a hypopharyngeal carcinoma in the gastrostomy tract), and in four patients in group B (three cases of peritonitis and one aspiration, resulting in two deaths), but in none of the group C patients. Group A patients experienced fewer peristomal infections than the other two groups (14%, 30%, and 41%, respectively: p = 0.05). The risk of peristomal pain was similar (11%, 15%, and 11%, respectively; p = n.s.). In three patients in group C, the PEG catheter had to be replaced by the pull method, due to repeated dislocation of the balloon catheter.\n The complication rate with PEG placement is high with both the push and pull methods. The complication rate with the pull method is significantly reduced when antibiotic prophylaxis is used.",
"When a patient needs enteral feeding, there are two methods to administer the nutrition. The method most used is the nasogastric tube (NGT), although in the literature little is published about the advantages and complications of the NGT. The second method is percutaneous endoscopic gastrostomy (PEG). A prospective randomized trial was started, and so far 90 patients have entered the study (46 NGT and 44 PEG). In four patients it was not possible to insert the NGT, and in three patients it was impossible to place the PEG. In both groups 6.5% aspiration was found. Nasal decubitus and swallowing problems were seen in 13% and 17%, respectively, in the NGT group. Intraperitoneal bleeding and abdominal pain were found in 2% and 11%, respectively, in the PEG group. Fixation of the patients was needed in 7% of the PEG and 22% in the NGT group. In eight patients in the NGT group the feeding had to be stopped owing to problems; in none of the PEG group was this necessary. The nursing staff awarded marks to each patient on a scale of 5 for the convenience of care (very good, 1; very bad, 5). This resulted in a mean score of 2.6 in the NGT and 2.0 in the PEG group. The score given by the patients was 2.3 in the NGT and 1.8 in the PEG group. There seems to be a clear preference for the PEG as a method for enteral nutrition.",
"Dysphagia following stroke is common problem and is of particular concern because of its potental for malnutrition. Nasogastric (NG) and percutaneous endoscopic gastrostomy (PEG) tube feeding are recognized methods for nutritional support for patients with persistent neurologic dysphagia. However, the former is associated with tube dislodgement and blockage that might compromise the patients' nutritional status. There have been few randomized prospective studies to date comparing the efficacy and safety of these 2 modes of dysphagia management in stroke patients. The objective of this study was to compare PEG with NG tube feeding after acute dysphagic stroke in terms of nutritional status and treatment failure. This was a randomized prospective clinical trial. A total of 23 consecutive patients who fulfilled the criteria were recruited from the medical wards in Hospital Universiti Kebangsaan Malaysia. The diagnosis of stroke (acute cerebral infarct) was based on clinical and brain computed tomographic (CT scan) findings; and the diagnosis of dysphagia was done clinically by using the 'swallowing test'. At recruitment, upper-arm skin fold thickness (triceps and biceps) and mid-arm circumference were measured; and blood was drawn for serum albumin level. They were then followed up at 4 weeks where the above tests were repeated. A total of 22 patients completed the study (12 patients in the NG group and 10 patients in the PEG group). Serum albumin levels (p = 0.045) were significantly higher in the PEG as compared to the NG group at 4 weeks post-intervention. There were statistically significant improvements in serum albumin level (p = 0.024) in the PEG group; and statistically significant reductions in serum albumin level (p = 0.047) in the NG group 4 weeks after the intervention. However, there were no significant differences in anthropometric parameters between the two groups and no significant changes in these parameters for each group 4 weeks after the intervention. Treatment failure occurred in 5 out of 10 patients (50.0%) in the NG group, but none in PEG group (p = 0.036). PEG tube feeding is more effective than NG tube feeding in improving the nutritional status (in terms of the serum albumin level) of patients with dysphagic stroke. NG tube feeding, in fact, reduced the nutritional status (in terms of the serum albumin level) of the patients.",
"Artificial feeding by a percutaneous endoscopic gastrostomy (PEG) tube in patients with dementia has increased since the introduction of the endoscopic method of tube placement. Few studies have documented survival benefit from this intervention. This report reviews our experience with PEG tube placement for feeding patients with dementia.\n All consultations for PEG tube placement were evaluated by a certified nutrition support nurse (L.M.M.) in consultation with a member of the gastroenterology physician staff (T.O.L.) for 24 months. Evaluation included the attainment of a brief medical history, a physical examination, and a review of comorbid conditions, laboratory variables for nutrition status, and bleeding risk. Interviews with patients or surrogates were conducted, including an explanation of the risks and benefits of PEG tube placement. A Kaplan-Meier survival curve was used to compare the median survival between patients with dementia who received a PEG tube and patients with dementia in whom PEG tube placement was refused.\n We received 41 consultations for PEG tube placement in patients with dementia. Percutaneous endoscopic gastrostomy was performed in 23 patients; 18 patients met the medical criteria for PEG tube placement, but surrogates refused placement. The median survival for the 23 patients who underwent PEG was 59 days; the median survival for the 18 patients who did not undergo PEG was 60 days.\n There seems to be no survival benefit in patients with dementia who receive artificial feeding by a PEG tube.",
"To determine the efficacy of antibiotic prophylaxis in percutaneous endoscopic gastrostomy (PEG) as a part of a standardized regimen.\n An open prospective randomised multicenter study in 216 patients. 106 received ceftriaxone 1 g i.v. 30 min preinterventionally and 110 no study medication. A standardized protocol was followed for PEG preparation, insertion, and aftercare; all patients received a 15 French gastrostomy tube. Follow-up of local and systemic infection and clinical course was continued to postintervention day 10. An aggregate erythema and exudation score > 3 or the presence of pus was taken as indicative of peristomal infection. The pharmacoeconomics of antibiotic use were also examined.\n In no-prophylaxis patients, wound infection rates were 23.6% on day 4 and 24.5% on day 10 vs. 7.6% (p < 0.05) and 11.4% (p < 0.05), respectively, in prophylaxis patients. Results were disproportionally better in tumor patients in comparison with neurological patients. Patients systemic infection rates were 11.8% vs. 1.9% in noprophylaxis vs. prophylaxis (p < 0.05), and overall infection rates 36.3% vs. 13.3%, respectively (p < 0.05). Pneumonia was more frequent in patients with underlying neurological disease and reduced in the prophylaxis group. Antibiotic and application costs were similar in both groups (p = 0.400).\n Single-dose ceftriaxone 1 g is a effective prophylaxis against local and systemic infection after PEG and should be a part of a standard regimen.",
"To investigate the effect of percutaneous endoscopic gastrostomy (PEG) on gastroesophageal reflux (GER) in mechanically-ventilated patients.\n In a prospective, randomized, controlled study 36 patients with recurrent or persistent ventilator-associated pneumonia (VAP) and GER > 6% were divided into PEG group (n = 16) or non-PEG group (n = 20). Another 11 ventilated patients without reflux (GER < 3%) served as control group. Esophageal pH-metry was performed by the \"pull through\" method at baseline, 2 and 7 d after PEG. Patients were strictly followed up for semi-recumbent position and control of gastric nutrient residue.\n A significant decrease of median (range) reflux was observed in PEG group from 7.8 (6.2 - 15.6) at baseline to 2.7 (0 - 10.4) on d 7 post-gastrostomy (P < 0.01), while the reflux increased from 9 (6.2 - 22) to 10.8 (6.3 - 36.6) (P < 0.01) in non-PEG group. A significant correlation between GER (%) and the stay of nasogastric tube was detected (r = 0.56, P < 0.01).\n Gastrostomy when combined with semi-recumbent position and absence of nutrient gastric residue reduces the gastroesophageal reflux in ventilated patients."
] |
PEG was associated with a lower probability of intervention failure, suggesting the endoscopic procedure is more effective and safe as compared to NGT. There is no significant difference of mortality rates between comparison groups, and pneumonia irrespective of underlying disease (medical diagnosis). Future studies should include previously planned and executed follow-up periods, the gastrostomy technique, and the experience of the professionals to allow more detailed subgroup analysis.
|
CD007772
|
[
"9580172"
] |
[
"Administration of antibiotics to patients with rupture of membranes at term: a prospective, randomized, multicentric study. Collaborative Group on PROM."
] |
[
"To assess whether antibiotic administration changes the rate of materno-fetal infectious morbidity in premature rupture of membranes occurring later than 35 weeks of gestation.\n A prospective, randomized and multicentric study in the Perinatology Units of eleven hospitals in Spain. Women were randomized to either antibiotic administration or control group. All were induced, if labor had not started spontaneously after 12 hours of ruptured membranes. Main outcome measures were maternal infection (chorioamnionitis and endometritis) and neonatal infectious morbidity (neonatal sepsis, meningitis and bronchopneumonia).\n Seven hundred and thirty-three patients were enrolled in the study, 371 in the antibiotics group and 362 in the control group. The incidence of chorioamnionitis and puerperal endometritis were reduced but the differences are statistically nonsignificant. However, the incidence of neonatal sepsis was significantly lower in newborns to mothers who had received antibiotics, 1 vs. 7 cases (Fisher's exact test, p<0.007).\n The study strongly suggests that prophylactic use of antibiotics in premature rupture of membranes occurring at 36 or more weeks of gestation reduces the risk of neonatal sepsis and probably maternal endometritis."
] |
Current evidence indicates that compared to placebo, antibiotics for MSAF in labour may reduce chorioamnionitis. There was no evidence that antibiotics could reduce postpartum endometritis, neonatal sepsis and NICU admission. This systematic review identifies the need for more well-designed, adequately powered RCTs to assess the effect of prophylactic antibiotics in the incidence of maternal and neonatal complications.
|
CD003477
|
[
"11730399",
"7823387",
"10391656",
"9746022",
"15161896",
"12161081",
"16505433"
] |
[
"Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses.",
"Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials.",
"Impact of study quality on outcome in placebo-controlled trials of homeopathy.",
"Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses?",
"Empirical evidence for selective reporting of outcomes in randomized trials: comparison of protocols to published articles.",
"The reporting of methodological factors in randomized controlled trials and the association with a journal policy to promote adherence to the Consolidated Standards of Reporting Trials (CONSORT) checklist.",
"Quality of randomized controlled trials reporting in the primary treatment of brain tumors."
] |
[
"To explore whether reported methodologic quality affects estimated intervention effects in randomized trials and contributes to discrepancies between the results of large randomized trials and small randomized trials in meta-analyses.\n Meta-analyses of randomized trials that included at least one large trial (>/=1000 participants) were included, regardless of the therapeutic area. Eligible meta-analyses were identified through electronic searches and bibliographies of relevant articles.\n Full-length randomized trials.\n Methodologic quality was assessed according to reported randomization, double blinding, and follow-up as separate components and by using the Jadad composite scale.\n Fourteen meta-analyses involving 190 randomized trials from eight therapeutic areas were included. Compared with large trials, intervention effects were exaggerated in small trials with inadequate allocation sequence generation (ratio of odds ratios, 0.46 [95% CI, 0.25 to 0.83]; P = 0.011), inadequate allocation concealment (ratio of odds ratios, 0.49 [CI, 0.27 to 0.86]; P = 0.014), and no double blinding (ratio of odds ratios, 0.52 [CI, 0.28 to 0.96]; P = 0.01). Large trials did not differ significantly from small trials with adequate generation of the allocation sequence, adequate allocation concealment, or adequate double blinding. No association was seen between reported follow-up and intervention effects. The Jadad scale provided no additional information because the scale and the quality components overlapped substantially.\n Inadequate generation of the allocation sequence, allocation concealment, and double blinding lead to exaggerated estimates of intervention benefit and may contribute to discrepancies between the results of large randomized trials and small randomized trials in meta-analyses.",
"To determine if inadequate approaches to randomized controlled trial design and execution are associated with evidence of bias in estimating treatment effects.\n An observational study in which we assessed the methodological quality of 250 controlled trials from 33 meta-analyses and then analyzed, using multiple logistic regression models, the associations between those assessments and estimated treatment effects.\n Meta-analyses from the Cochrane Pregnancy and Childbirth Database.\n The associations between estimates of treatment effects and inadequate allocation concealment, exclusions after randomization, and lack of double-blinding.\n Compared with trials in which authors reported adequately concealed treatment allocation, trials in which concealment was either inadequate or unclear (did not report or incompletely reported a concealment approach) yielded larger estimates of treatment effects (P < .001). Odds ratios were exaggerated by 41% for inadequately concealed trials and by 30% for unclearly concealed trials (adjusted for other aspects of quality). Trials in which participants had been excluded after randomization did not yield larger estimates of effects, but that lack of association may be due to incomplete reporting. Trials that were not double-blind also yielded larger estimates of effects (P = .01), with odds ratios being exaggerated by 17%.\n This study provides empirical evidence that inadequate methodological approaches in controlled trials, particularly those representing poor allocation concealment, are associated with bias. Readers of trial reports should be wary of these pitfalls, and investigators must improve their design, execution, and reporting of trials.",
"We investigated the influence of indicators of methodological quality on study outcome in a set of 89 placebo-controlled clinical trials of homoeopathy in three different ways: (1) The results of studies meeting single criteria (explicit statement of random allocation, allocation concealment, double-blinding, completeness of follow-up) of methodological quality were compared with those of studies not meeting the criteria in univariate and multivariate analyses; (2) The results of studies scoring above and below predefined scores in two quality assessment scales were compared; (3) Primary studies were consecutively entered into a cumulative meta-analysis according to the summary scores derived from the quality assessment scales. All analyses were performed using meta-regression methods. Studies that were explicitly randomized and were double-blind as well as studies scoring above the cut-points yielded significantly less positive results than studies not meeting the criteria. In the cumulative meta-analyses, there was a trend for increasing effect sizes when more studies with lower-quality scores were added. However, there was no linear relationship between quality scores and study outcome. We conclude that in the study set investigated, there was clear evidence that studies with better methodological quality tended to yield less positive results. Because summarizing disparate study features into a single score is problematic, meta-regression methods simultaneously investigating the influence of single study features seem the best method for investigating the impact of study quality on outcome.",
"Few meta-analyses of randomised trials assess the quality of the studies included. Yet there is increasing evidence that trial quality can affect estimates of intervention efficacy. We investigated whether different methods of quality assessment provide different estimates of intervention efficacy evaluated in randomised controlled trials (RCTs).\n We randomly selected 11 meta-analyses that involved 127 RCTs on the efficacy of interventions used for circulatory and digestive diseases, mental health, and pregnancy and childbirth. We replicated all the meta-analyses using published data from the primary studies. The quality of reporting of all 127 clinical trials was assessed by means of component and scale approaches. To explore the effects of quality on the quantitative results, we examined the effects of different methods of incorporating quality scores (sensitivity analysis and quality weights) on the results of the meta-analyses.\n The quality of trials was low. Masked assessments provided significantly higher scores than unmasked assessments (mean 2.74 [SD 1.10] vs 2.55 [1.20]). Low-quality trials (score < or = 2), compared with high-quality trials (score > 2), were associated with an increased estimate of benefit of 34% (ratio of odds ratios [ROR] 0.66 [95% CI 0.52-0.83]). Trials that used inadequate allocation concealment, compared with those that used adequate methods, were also associated with an increased estimate of benefit (37%; ROR=0.63 [0.45-0.88]). The average treatment benefit was 39% (odds ratio [OR] 0.61 [0.57-0.65]) for all trials, 52% (OR 0.48 [0.43-0.54]) for low-quality trials, and 29% (OR 0.71 [0.65-0.77]) for high-quality trials. Use of all the trial scores as quality weights reduced the effects to 35% (OR 0.65 [0.59-0.71]) and resulted in the least statistical heterogeneity.\n Studies of low methodological quality in which the estimate of quality is incorporated into the meta-analyses can alter the interpretation of the benefit of intervention, whether a scale or component approach is used in the assessment of trial quality.",
"Selective reporting of outcomes within published studies based on the nature or direction of their results has been widely suspected, but direct evidence of such bias is currently limited to case reports.\n To study empirically the extent and nature of outcome reporting bias in a cohort of randomized trials.\n Cohort study using protocols and published reports of randomized trials approved by the Scientific-Ethical Committees for Copenhagen and Frederiksberg, Denmark, in 1994-1995. The number and characteristics of reported and unreported trial outcomes were recorded from protocols, journal articles, and a survey of trialists. An outcome was considered incompletely reported if insufficient data were presented in the published articles for meta-analysis. Odds ratios relating the completeness of outcome reporting to statistical significance were calculated for each trial and then pooled to provide an overall estimate of bias. Protocols and published articles were also compared to identify discrepancies in primary outcomes.\n Completeness of reporting of efficacy and harm outcomes and of statistically significant vs nonsignificant outcomes; consistency between primary outcomes defined in the most recent protocols and those defined in published articles.\n One hundred two trials with 122 published journal articles and 3736 outcomes were identified. Overall, 50% of efficacy and 65% of harm outcomes per trial were incompletely reported. Statistically significant outcomes had a higher odds of being fully reported compared with nonsignificant outcomes for both efficacy (pooled odds ratio, 2.4; 95% confidence interval [CI], 1.4-4.0) and harm (pooled odds ratio, 4.7; 95% CI, 1.8-12.0) data. In comparing published articles with protocols, 62% of trials had at least 1 primary outcome that was changed, introduced, or omitted. Eighty-six percent of survey responders (42/49) denied the existence of unreported outcomes despite clear evidence to the contrary.\n The reporting of trial outcomes is not only frequently incomplete but also biased and inconsistent with protocols. Published articles, as well as reviews that incorporate them, may therefore be unreliable and overestimate the benefits of an intervention. To ensure transparency, planned trials should be registered and protocols should be made publicly available prior to trial completion.",
"The \"Consolidated Standards of Reporting Trials\" (CONSORT) was developed to improve the suboptimal reporting of randomized controlled trials (RCTs). However, little is known about the quality of reporting since this publication. We undertook an observational study to determine the quality of reporting key methodological factors in RCTs since the publication of the CONSORT statement and if a journal policy to promote adherence to the CONSORT checklist was associated with superior reporting. We recorded the reporting of 11 key methodological factors in 105 RCTs from 29 medical journals published subsequent to the CONSORT statement. We examined the quality of reporting in relation to whether a journal was a \"CONSORT promoter\" as defined by inclusion of the CONSORT checklist in a journal's \"information to authors\" section or a requirement that authors, manuscript reviewers, or copy editors complete the CONSORT checklist. Multivariate analysis controlled for journal impact factor, study outcome, and time of publication. Six of the 11 methodological factors were reported <50% of the time. The number of methodological factors reported was greater in CONSORT promoters than in journals not promoting CONSORT in both unadjusted (6.0 and 5.1, respectively, p-value = 0.03) and adjusted (6.4 and 4.8 of the 11 methodological factors, respectively, p-value = 0.0001) analyses. While journals that promote CONSORT demonstrate superior reporting of RCTs, persistent inadequacies in reporting remain. Until these inadequacies are resolved health-care providers will remain limited in their ability to make informed inferences about the validity of the studies upon which they base their clinical practice.",
"To assess the reporting quality of randomized controlled trials (RCTs) in the primary treatment of brain tumors and to identify significant predictors of quality.\n Two investigators searched MEDLINE, EMBASE, and bibliographies of retrieved articles for RCTs in the primary treatment of brain tumors published between January 1990 and December 2004. We assessed the quality of overall reporting and key methodologic factors reporting (allocation concealment, blinding, and intention to treat [ITT]). Two investigators also rated articles independently using items from the revised Consolidated Standards of Reporting Trials statement. A generalized estimated equation was used to generate regression models that identified significant factors associated with quality of reporting.\n We retrieved 74 relevant RCTs that randomly assigned 14,498 brain tumor patients. The quality of overall reporting has improved during the last 15 years, but eight of the 15 methodologic items were reported in less than 50% of trials. In the appraisal of the reporting quality of key methodologies, allocation concealment, blinding, and adherence to the ITT principle were reported in less than 30% of articles. Multivariable regression models revealed that an impact factor more than 1.66, publication after 1995, and sample size more than 280 were significant factors associated with better overall reporting, whereas complete industrial funding, impact factors more than 2.64, and positive primary outcomes were predictors of higher ratings of the three most important methodologic qualities.\n Despite improvement in general reporting quality, key methodologies that safeguard against biases may still benefit from better description. Significant factors associated with better reporting may act as surrogates for other characteristics."
] |
The methodological quality and the reporting of the included studies were too poor to draw any useful conclusions.
|
CD003047
|
[
"10928571",
"7675964",
"12644958",
"10757573"
] |
[
"Chronic effects of dopaminergic replacement on cognitive function in Parkinson's disease: a two-year follow-up study of previously untreated patients.",
"Benzodiazepine receptor antagonism improves reaction time in latent hepatic encephalopathy.",
"The efficacy of flumazenil in subclinical to mild hepatic encephalopathic ambulatory patients. A prospective, randomised, double-blind, placebo-controlled study.",
"Low-dose dopexamine in patients undergoing hemihepatectomy: an evaluation of effects on reduction of hepatic dysfunction and ischaemic liver injury."
] |
[
"The cognitive effects of dopaminergic treatment in Parkinson's disease (PD) are still controversial.\n To evaluate, in previously untreated patients with PD, whether chronic dopaminergic stimulation produces significant cognitive changes; whether they are sustained beyond the period of a few months; and whether the cognitive status of two motor-comparable groups is differently affected by levodopa and pergolide.\n Parallel, randomized open study with blind neuropsychologic evaluation of 20 consecutive de novo patients with PD before and 3, 6, 12, 18, and 24 months after monotherapy with levodopa (n = 10) or pergolide (n = 10; 6-month monotherapy; pergolide + levodopa thereafter).\n Both treatments were associated with a significant improvement in motor scores and in tests assessing learning and long-term verbal and visual memory, visuospatial abilities, and various frontal tasks. While improvement in motor scores persisted, improvement in activities of daily living and in semantic fluency, Luria's rhythm and motor and long-term memory tests was not sustained at the 24-month examination. Further, performance on attentional, short-term memory, and the Stroop tests did not change over the course of the study.\n Both treatments were associated with incomplete but long-lasting (18 mos) improvement in many cognitive tasks which declined thereafter, suggesting that dopaminergic replacement is not enough to compensate for all cognitive deficits of PD.",
"Endogenous benzodiazepine-like substances are thought to play a role in the development of hepatic encephalopathy (HE). Ten patients with sub-clinical or latent hepatic encephalopathy (LHE) and ten normal controls were cognitively assessed pre- and post-infusion of 0.2 mg of the benzodiazepine (BZ) antagonist flumazenil in a placebo-controlled, cross-over, double-blind design. Flumazenil infusion resulted in a significant improvement in simple reaction time in patients, but not in controls. Saline infusion had no effect on any of the cognitive measures in either group. Flumazenil appeared to have a particular enhancing effect on the cognitive, as opposed to the motor, component of the reaction time task. This finding supports the view that the benzodiazepine/GABA system is implicated in the bradyphrenia that is characteristic of chronic liver disease, even before hepatic encephalopathy is apparent. We conclude that benzodiazepine receptor antagonism may improve cognitive function, particularly speed of information processing, in patients with latent hepatic encephalopathy.",
"Hepatic encephalopathy (HE) is a neuropsychiatric syndrome associated with fulminant hepatic failure and chronic liver disease. Its pathogenesis is unclear. One of the factors implicated is enhanced GABA-ergic tone, which is probably related to increased concentrations of cerebral benzodiazepine (BNZ). In the present study, we tested flumazenil, a cerebral BNZ antagonist, in cirrhosis patients with hepatic encephalopathy.\n Out of 47 patients, 7 were excluded prior to randomization for various reasons. Twenty patients were included in the flumazenil group and 20 in the placebo group in a prospective, randomized, double-blind, placebo-controlled study. Patients were given flumazenil (1 mg/h, continuous IV infusion) or an equal volume of saline solution for 5 hours. Before and after treatment, portosystemic encephalopathy (PSE) stage and number connection test (NCT) scores were checked every half hour for 5 hours. EEG was recorded 15 minutes before and 1 hour after treatment.\n While significant improvements were determined in PSE stage and NCT score in the flumazenil group, there were no such improvements in the placebo group. There was no statistically significant difference between pre- and post-treatment EEGs in either group.\n It was concluded that continuous IV infusion of flumazenil had beneficial and safe effects in the treatment of hepatic encephalopathy patients.",
"Hepatic dysfunction is a common problem in patients after hemihepatectomy. Treatment with low-dose dopamine has been shown to be beneficial in hemihepatectomy patients. We hypothesized that dopexamine, a synthetic vasoactive catecholamine, due to its specific pharmocodynamic profile may be more effective in reducing hidden ischaemic episodes in the hepato-splanchnic region during and after temporary total cross-clamping of hepatic inflow in these patients.\n The effects of low-dose dopexamine on hepatic venous haemoglobin oxygen saturation (ShvO2), hepatic venous lactate level, monoethylglycinxylid (MEGX) formation, hepatic synthetic function and indicators for hepatic cell damage were studied during hemihepatectomy and for 16 h postoperatively in hemihepatectomy patients and compared to those of low-dose dopamine. In a prospective, double-blind clinical study 20 patients received randomly either dopexamine (DPX) 0.5 microg kg(-1) min(-1) (n=10) or dopamine (DO) 2.5 microg kg(-1) min(-1) (n= 10). Infusions were started after induction of anaesthesia and continued 16 h postoperatively. Hepatic vein, radial and pulmonary artery were catheterized. Measurements were carried out after induction of anaesthesia, after total cross-clamping of hepatic inflow, and at 2 h and 16 h postoperatively.\n There were no differences in systemic haemodynamics, oxygenation, ShvO2, serum aminotransferases or MEGX levels between the groups. At 16 h postoperatively prothrombin and antithrombin III levels were significantly lower while hepatic venous lactate was significantly higher in the DPX group compared to the DO group.\n In patients undergoing hemihepatectomy, we could not reveal superior hepatoprotective effects of low-dose dopexamine compared to low-dose dopamine."
] |
This review does not provide evidence that dopaminergic agonists are of benefit to patients with acute or chronic hepatic encephalopathy, or fulminant hepatic failure. The review is limited by the small number of trials performed within this field, the low number of patients randomised in each trial, and the low methodological quality of included trials. Accordingly, there is also insufficient evidence to exclude a potential beneficial effect. Dopaminergic agonists should not be used for hepatic encephalopathy, but may be assessed in future randomised clinical trials.
|
CD001256
|
[
"8238713",
"17940147",
"11850308",
"11796769",
"19234513",
"15105515",
"19109444",
"11207837",
"21436390",
"19704158",
"17653942",
"18547863",
"17908562",
"11493843",
"15302725",
"17252176",
"11239307",
"17654228",
"19675115"
] |
[
"Prevention of running injuries by warm-up, cool-down, and stretching exercises.",
"No effect of a graded training program on the number of running-related injuries in novice runners: a randomized controlled trial.",
"Intensive physical training in geriatric patients after severe falls and hip surgery.",
"Community based rehabilitation after severe traumatic brain injury: a randomised controlled trial.",
"A randomized trial on the effect of a multimodal intervention on physical capacity, functional performance and quality of life in adult patients undergoing allogeneic SCT.",
"High-intensity resistance training improves muscle strength, self-reported function, and disability in long-term stroke survivors.",
"Effects of conventional physical therapy and functional strength training on upper limb motor recovery after stroke: a randomized phase II study.",
"Exercise training for rehabilitation and secondary prevention of falls in geriatric patients with a history of injurious falls.",
"Effects of treatment intensity in upper limb robot-assisted therapy for chronic stroke: a pilot randomized controlled trial.",
"Efficacy of functional strength training on restoration of lower-limb motor function early after stroke: phase I randomized controlled trial.",
"Does intensive rehabilitation improve the functional outcome of patients with traumatic brain injury (TBI)? A randomized controlled trial.",
"Effect of water immersion methods on post-exercise recovery from simulated team sport exercise.",
"Comparison of a functional restoration program with active individual physical therapy for patients with chronic low back pain: a randomized controlled trial.",
"A randomized controlled trial to prevent patient lift and transfer injuries of health care workers.",
"Inspiratory muscle training improves lung function and exercise capacity in adults with cystic fibrosis.",
"Mild traumatic brain injuries: the impact of early intervention on late sequelae. A randomized controlled trial.",
"The effect of aerobic training on rehabilitation outcomes after recent severe brain injury: a randomized controlled evaluation.",
"Influence of cold-water immersion on indices of muscle damage following prolonged intermittent shuttle running.",
"Effectiveness of a video-based exercise programme to reduce falls and improve health-related quality of life among older adults discharged from hospital: a pilot randomized controlled trial."
] |
[
"The purpose of this study was to evaluate the effect of a health education intervention on running injuries. The intervention consisted of information on, and the subsequent performance of, standardized warm-up, cool-down, and stretching exercises. Four hundred twenty-one male recreational runners were matched for age, weekly running distance, and general knowledge of preventing sports injuries. They were randomly split into an intervention and a control group: 167 control and 159 intervention subjects participated throughout the study. During the 16-week study, both groups kept a daily diary on their running distance and time, and reported all injuries. In addition, the intervention group was asked to note compliance with the standardized program. At the end of the study period, knowledge and attitude were again measured. There were 23 injuries in the control group and 26 in the intervention group. Injury incidence for control and intervention subjects was 4.9 and 5.5 running injuries per 1000 hours, respectively. The intervention was not effective in reducing the number of running injuries; it proved significantly effective (P < 0.05) in improving specific knowledge of warm-up and cool-down techniques in the intervention group. This positive change can perhaps be regarded as a first step on the way to a change of behavior, which may eventually lead to a reduction of running injuries.",
"Although running has positive effects on health and fitness, the incidence of a running-related injury (RRI) is high. Research on prevention of RRI is scarce; to date, no studies have involved novice runners.\n A graded training program for novice runners will lead to a decrease in the absolute number of RRIs compared with a standard training program.\n Randomized controlled trial; Level of evidence, 1.\n GRONORUN (Groningen Novice Running) is a 2-armed randomized controlled trial comparing a standard 8-week training program (control group) and an adapted, graded, 13-week training program (intervention group), on the risk of sustaining an RRI. Participants were novice runners (N = 532) preparing for a recreational 4-mile (6.7-km) running event. The graded 13-week training program was based on the 10% training rule. Both groups registered information on running characteristics and RRI using an Internet-based running log. The primary outcome measure was RRIs per 100 participants. An RRI was defined as any musculoskeletal complaint of the lower extremity or back causing a restriction of running for at least 1 week.\n The graded training program was not preventive for sustaining an RRI (chi(2) = 0.016, df = 1, P = .90). The incidence of RRI was 20.8% in the graded training program group and 20.3% in the standard training program group.\n This randomized controlled trial showed no effect of a graded training program (13 weeks) in novice runners, applying the 10% rule, on the incidence of RRI compared with a standard 8-week training program.",
"Intensive exercise training can lead to improvement in strength and functional performance in older people living at home and nursing home residents. There is little information whether intensive physical exercise may be applicable and effective in elderly patients suffering from the acute sequelae of injurious falls or hip surgery.\n To assess the feasibility, safety and efficacy of intensive, progressive physical training in rehabilitation after hip surgery.\n Prospective, randomised, placebo-controlled intervention study of a 3-months training intervention and a 3-months' follow-up.\n Physical training 6-8 weeks after hip surgery.\n Twenty-eight (15 intervention, 13 control) elderly patients with a history of injurious falls admitted to acute care or inpatient rehabilitation because of acute fall-related hip fracture or elective hip replacement.\n Progressive resistance and functional training to improve strength and functional performance.\n No training-related medical problems occurred in the study group. Twenty-four patients (86%) completed all assessments during the intervention and follow-up period. Adherence was excellent in both groups (intervention: 93, 0+/-13, 5% versus control: 96, 7+/-6, 2%). Training significantly increased strength, functional motor performance and balance and reduced fall-related behavioural and emotional problems. Some improvements in strength persisted during 3-months follow-up while other strength variables and functional performances were lost after cessation of training. Patients in the control group showed no change in strength, functional performance and emotional state during intervention and follow-up.\n Progressive resistance training and progressive functional training are safe and effective methods to increase strength and functional performance during rehabilitation in patients after hip surgery and a history of injurious falls. Because part of the training improvements were lost after stopping the training, a continuing training regime should be established.",
"Evaluation of multidisciplinary community based outreach rehabilitation after severe traumatic brain injury (TBI).\n A randomised controlled trial compared outreach treatment (mean of two sessions a week for 27.3 (SD 19.1) weeks) in community settings such as participants' homes, day centres, or workplaces, with provision of written information detailing alternative resources. Follow up for an average of 24.8 months after initial allocation was by a blinded independent assessor. Participants were aged 16-65, had sustained severe TBI between 3 months and 20 years previously, and had no other neurological conditions. Of 110 initially allocated, 48 outreach and 46 information participants were successfully followed up. Primary outcome measures (Barthel index (BI) and the brain injury community rehabilitation outcome-39 (BICRO-39)) focused on levels of activity and participation. Secondary measures were the functional independence measure and the functional assessment measure (FIM+FAM) and, in a subgroup of 46 participants, the hospital anxiety and depression scale. Analyses were non-parametric.\n outreach participants were significantly more likely to show gains on the BI and the BICRO-39 total score and self organisation and psychological wellbeing subscales. There were likewise strong trends (p<0.10) for BICRO personal care and mobility, and on the FIM+FAM for personal care and cognitive functions. Differential improvements were not seen for indices of socializing, productive employment, anxiety, or depression. Median changes on individual subscales were small, reflecting the diversity of the clinical population; however, 40% of outreach but only 20% of information participants made a clinically significant improvement of 2+ points on at least one BICRO-39 scale. Time since injury was unrelated to the magnitude of gains.\n This is the first RCT of multidisciplinary community rehabilitation after severe TBI, and suggests that even years after injury it can yield benefits which outlive the active treatment period.",
"The aim of this randomized controlled trial was to investigate the effect of a 4- to 6-week multimodal program of exercise, relaxation and psychoeducation on physical capacity, functional performance and quality of life (QOL) in allogeneic hematopoietic cell transplantation (allo-HSCT) adult recipients. In all, 42 patients were randomized to a supervised multimodal intervention or to a control group receiving usual care. The primary end point was on aerobic capacity measured in VO(2) max. Secondary end points were muscle strength, functional performance, physical activity level, QOL, fatigue, psychological well-being and clinical outcomes. The multimodal intervention had a significant effect on physical capacity: VO(2) max (P<0.0001) and muscle strength: chest press (P<0.0001), leg extension (P=0.0003), right elbow flexor (P=0.0009), right knee extensor (P<0.0001) and functional performance (stair test) (0.0008). Moreover, the intervention group showed significantly better results for the severity of diarrhea (P=0.014) and fewer days of total parenteral nutrition (P=0.019). Longitudinal changes in QOL, fatigue and psychological well-being favored the intervention group, but did not reach statistical significance. Assignment of a multimodal intervention during allo-HSCT did not cause untoward events, sustained aerobic capacity and muscle strength and reduced loss of functional performance during hospitalization.",
"To evaluate the efficacy of supervised high-intensity progressive resistance training (PRT) on lower extremity strength, function, and disability in older, long-term stroke survivors.\n Forty-two volunteers aged 50 years and above, 6 months to 6 years after a single mild to moderate stroke, were randomized into either a control group of upper extremity stretching or a PRT group that received a 12-week supervised high-intensity resistance training program consisting of bilateral leg press (LP), unilateral paretic and nonparetic knee extension (KE), ankle dorsiflexion (DF), and plantarflexion (PF) exercises. Functional performance was assessed using the 6-minute walk, stair-climb time, repeated chair-rise time, and habitual and maximal gait velocities. Self-reported changes in function and disability were evaluated using the Late Life Function and Disability Instrument (LLFDI).\n Single-repetition maximum strength significantly improved in the PRT group for LP (16.2%), paretic KE (31.4%), and nonparetic KE (38.2%) with no change in the control group. Paretic ankle DF (66.7% versus -24.0%), paretic ankle PF (35.5% versus -20.3%), and nonparetic ankle PF (14.7% versus -13.8%) significantly improved in the PRT group compared with the control. The PRT group showed significant improvement in self-reported function and disability with no change in the control. There was no significant difference between groups for any performance-based measure of function.\n High-intensity PRT improves both paretic and nonparetic lower extremity strength after stroke, and results in reductions in functional limitations and disability.",
"Functional training and muscle strength training may improve upper limb motor recovery after stroke. Combining these as functional strength training (FST) might enhance the benefit, but it is unclear whether this is better than conventional physical therapy (CPT). Comparing FST with CPT is not straightforward.\n This study aimed at assessing the feasibility of conducting a phase III trial comparing CPT with FST for upper limb recovery.\n Randomized, observer-blind, phase II trial. Subjects had upper limb weakness within 3 months of anterior circulation infarction. Subjects were randomized to CPT (no extra therapy), CPT + CPT, and CPT + FST. Intervention lasted 6 weeks. Primary outcome measure was the Action Research Arm Test (ARAT). Measurements were taken before treatment began, after 6 weeks of intervention, and 12 weeks thereafter. Attrition rate was calculated and differences between groups were interpreted using descriptive statistics. ARAT data were used to inform a power calculation.\n Thirty subjects were recruited (8% of people screened). Attrition rate was 6.7% at outcome and 40% at follow-up. At outcome the CPT + FST group showed the largest increase in ARAT score and this was above the clinically important level of 5.7 points. Median (interquartile range) increases were 11.5 (21.0) for CPT; 8.0 (13.3) for CPT + CPT; and 19.5 (22.0) for CPT + FST. The estimated sample size for an adequately powered subsequent phase III trial was 279 subjects at outcome.\n Further work toward a phase III clinical trial appears justifiable.",
"To determine the safety and efficacy of an exercise protocol designed to improve strength, mobility, and balance and to reduce subsequent falls in geriatric patients with a history of injurious falls.\n A randomized controlled 3-month intervention trial, with an additional 3-month follow-up.\n Out-patient geriatric rehabilitation unit.\n Fifty-seven female geriatric patients (mean age 82 +/- 4.8 years; range 75-90) admitted to acute care or inpatient rehabilitation with a history of recurrent or injurious falls including patients with acute fall-related fracture.\n Ambulatory training of strength, functional performance, and balance 3 times per week for 3 months. Patients of the control group attended a placebo group 3 times a week for 3 months. Both groups received an identical physiotherapeutic treatment 2 times a week, in which strengthening and balance training were excluded.\n Strength, functional ability, motor function, psychological parameters, and fall rates were assessed by standardized protocols at the beginning (T1) and the end (T2) of intervention. Patients were followed up for 3 months after the intervention (T3).\n No training-related medical problems occurred in the study group. Forty-five patients (79%) completed all assessments after the intervention and follow-up period. Adherence was excellent in both groups (intervention 85.4 +/- 27.8% vs control 84.2 +/- 29.3%). The patients in the intervention group increased strength, functional motor performance, and balance significantly. Fall-related behavioral and emotional restrictions were reduced significantly. Improvements persisted during the 3-month follow-up with only moderate losses. For patients of the control group, no change in strength, functional performance, or emotional status could be documented during intervention and follow-up. Fall incidence was reduced nonsignificantly by 25% in the intervention group compared with the control group (RR:0.753 CI:0.455-1.245).\n Progressive resistance training and progressive functional training are safe and effective methods of increasing strength and functional performance and reducing fall-related behavioral and emotional restrictions during ambulant rehabilitation in frail, high-risk geriatric patients with a history of injurious falls.",
"Robot-assisted therapy (RT) is a current promising intervention in stroke rehabilitation, but more research is warranted for examining its efficacy and the dose-benefit relation. The authors investigated the effects of higher intensity versus lower intensity RT on movements of forearm pronation-supination and wrist flexion-extension relative to conventional rehabilitation (CR) in patients poststroke for a mean of 21 months.\n In this pilot study, 18 patients with initial mean Fugl-Meyer Assessment (FMA) of 37 to 44 for the upper extremity were randomized to higher intensity RT, lower intensity RT, or CR intervention for 4 weeks. The dose of the higher intensity RT was twice the number of repetitions in the lower intensity RT. Outcome measures at pretreatment and posttreatment were administered to patients to evaluate beneficial and adverse effects of interventions. Primary outcomes were the FMA and Medical Research Council scale.\n There were significant differences in motor function (P = .04) and daily performance (P = .03) among the 3 groups. The higher intensity RT group showed better improvement in motor function, muscle strength, performance of daily activities, and bimanual ability than the other 2 groups. The intensive RT intervention did not induce higher levels of an oxidative DNA biomarker.\n Higher intensity of RT that assists forearm and wrist movements may lead to greater improvement in motor ability and functional performance in stroke patients. A sample size of only 20 to 25 in each arm of a larger randomized controlled trial is needed to confirm the findings for similar subjects.",
"After stroke, physiotherapy can promote brain reorganization and motor recovery. Combining muscle strength and functional training (functional strength training, FST) may be beneficial. The aim of the authors was to compare FST with conventional physiotherapy (CPT) while controlling for the potential confounder of therapy intensity in a multicenter, randomized controlled observer-blind trial. The mean age of the participants was 68.3 (standard deviation [SD] = 12.03) years at a mean of 34 (SD = 20) days after stroke, with mean peak paretic knee extension torque (torque) of 22 (SD = 25) Nm. The estimated sample size was 102 to detect a between-group difference of 0.2 m/s in walking speed. After baseline measures, participants were allocated randomly to CPT or CPT + CPT or CPT + FST for 6 weeks. Additional experimental therapy was provided for up to 1 hour a day, 4 times each week. Outcomes were measured 6 weeks after baseline and at follow-up 12 weeks thereafter.\n included walking speed, knee extensor torque, and functional mobility (Rivermead). At outcome, both extraintensity groups showed greater increases in walking speed than the CPT group, but this reached significance only for the CPT + CPT group (P = .031). The CPT + CPT group also had a greater number of participants who walked at 0.8 m/s or above. No significant differences were observed for torque about the knee or for the Rivermead score. At follow-up, no significant differences were observed. These phase I results justify a subsequent trial of CPT + CPT versus CPT + FST.",
"To evaluate the effects of an increase in the intensity of rehabilitation on the functional outcome of patients with traumatic brain injury (TBI).\n Sixty-eight patients (age 12-65 years) with moderate-to-severe TBI were included. They were randomized into high (4-hour/day) or control (2-hour/day) intensity rehabilitation programmes at an average of 20 days after the injury. The programmes ended when the patients achieved independence in daily activities or when 6 months had passed.\n No significant differences were found in the Functional Independence Measure (FIM) (primary outcome) and Neurobehavioural Cognitive Status Examination (NCSE) total scores between the two groups. There were significantly more patients in the high intensity group than in the control group who achieved a maximum FIM total score at the third month (47% vs. 19%, p = 0.015) and a maximum Glasgow Outcome Scale (GOS) score at the second (28% vs. 8%, p = 0.034) and third months (34% vs. 14%, p = 0.044).\n Early intensive rehabilitation may improve the functional outcome of patients with TBI in the early months post-injury and hence increase the chance of their returning to work early. Intensive rehabilitation in this study speeded up recovery rather than changed the final outcome.",
"This study aimed to compare the efficacy of hot/cold contrast water immersion (CWI), cold-water immersion (COLD) and no recovery treatment (control) as post-exercise recovery methods following exhaustive simulated team sports exercise. Repeated sprint ability, strength, muscle soreness and inflammatory markers were measured across the 48-h post-exercise period. Eleven male team-sport athletes completed three 3-day testing trials, each separated by 2 weeks. On day 1, baseline measures of performance (10 m x 20 m sprints and isometric strength of quadriceps, hamstrings and hip flexors) were recorded. Participants then performed 80 min of simulated team sports exercise followed by a 20-m shuttle run test to exhaustion. Upon completion of the exercise, and 24h later, participants performed one of the post-exercise recovery procedures for 15 min. At 48 h post-exercise, the performance tests were repeated. Blood samples and muscle soreness ratings were taken before and immediately after post-exercise, and at 24h and 48 h post-exercise. In comparison to the control and CWI treatments, COLD resulted in significantly lower (p<0.05) muscle soreness ratings, as well as in reduced decrements to isometric leg extension and flexion strength in the 48-h post-exercise period. COLD also facilitated a more rapid return to baseline repeated sprint performances. The only benefit of CWI over control was a significant reduction in muscle soreness 24h post-exercise. This study demonstrated that COLD following exhaustive simulated team sports exercise offers greater recovery benefits than CWI or control treatments.",
"To compare the short-term outcomes of active individual therapy (AIT) with those of a functional restoration program (FRP).\n Prospective randomized controlled study.\n Two rehabilitation centers and private ambulatory physiotherapy facilities.\n One hundred thirty-two adults with chronic low back pain. Fifty-one percent of patients on sick leave or out of work (mean duration, 180d in the 2y before treatment).\n For 5 weeks, FRP (at 25h/wk) or AIT (at 3h/wk).\n Trunk flexibility, back flexor, and extensor endurance (Ito and Sorensen tests), general endurance, pain intensity, Dallas Pain Questionnaire (DPQ) scores, daily activities, anxiety depression, social interest, and work and leisure activities, and self-reported improvement (work ability, resumption of sport and leisure activities).\n All outcome measures improved after treatment except endurance in AIT. There was no between-group difference for pain intensity or DPQ daily activities or work and leisure activities scores. Better results were observed in FRP for all other outcome measures. There was a significant effect of treatment and the initial value for the gain of the Sorensen score with a treatment or initial value interaction; a significant effect of treatment and initial value on the gains of Ito, endurance, and DPQ social interest and anxiety depression scores, with no treatment or initial value interaction; and a significant effect of initial value but not treatment for the gains of DPQ daily activities and work and leisure activities scores.\n Low-cost ambulatory AIT is effective. The main advantage of FRP is improved endurance. We speculate that this may be linked to better self-reported work ability and more frequent resumption of sports and leisure activities.",
"Randomized controlled trial (RCT).\n To compare the effectiveness of training and equipment to reduce musculoskeletal injuries, increase comfort, and reduce physical demands on staff performing patient lifts and transfers at a large acute care hospital.\n Back injury to nursing staff during patient handling tasks is a major issue in health care. The value of mechanical assistive devices in reducing injuries to these workers is unclear.\n This three-armed RCT consisted of a \"control arm,\" a \"safe lifting\" arm, and a \"no strenuous lifting\" arm. A medical, surgical, and rehabilitation ward were each randomly assigned to each arm. Both intervention arms received intensive training in back care, patient assessment, and handling techniques. Hence, the \"safe lifting\" arm used improved patient handling techniques using manual equipment, whereas the \"no strenuous lifting\" arm aimed to eliminate manual patient handling through use of additional mechanical and other assistive equipment.\n Frequency of manual patient handling tasks was significantly decreased on the \"no strenuous lifting\" arm. Self-perceived work fatigue, back and shoulder pain, safety, and frequency and intensity of physical discomfort associated with patient handling tasks were improved on both intervention arms, but staff on the mechanical equipment arm showed greater improvements. Musculoskeletal injury rates were not significantly altered.\n The \"no strenuous lifting\" program, which combined training with assured availability of mechanical and other assistive patient handling equipment, most effectively improved comfort with patient handling, decreased staff fatigue, and decreased physical demands. The fact that injury rates were not statistically significantly reduced may reflect the less sensitive nature of this indicator compared with the subjective indicators.",
"To investigate the effects of high-intensity inspiratory muscle training (IMT) on inspiratory muscle function (IMF), diaphragm thickness, lung function, physical work capacity (PWC), and psychosocial status in patients with cystic fibrosis (CF).\n Twenty-nine adult patients with CF were randomly assigned to three groups. Two groups were required to complete an 8-week program of IMT in which the training intensity was set at either 80% of maximal effort (group 1; 9 patients) or 20% of maximal effort (group 2; 10 patients). A third group of patients did not participate in any form of training and acted as a control group (group 3; 10 patients).\n In all patients, baseline and postintervention measures of IMF were determined by maximal inspiratory pressure (Pimax), and sustained Pimax (SPimax); pulmonary function, body composition, and physical activity status were also determined. In addition, diaphragm thickness was measured at functional residual capacity (FRC) and total lung capacity (TLC) [TDIcont], and the diaphragm thickening ratio (TR) was calculated (TR = thickness during Pimax at FRC/mean thickness at FRC). Subjects also completed an incremental cycle ergometer test to exhaustion and two symptom-related questionnaires, prior to and following training.\n Following training, significant increases in Pimax and SPimax (p < 0.05), TDIcont (p < 0.05), TR (p < 0.05), vital capacity (p < 0.05), TLC (p < 0.05), and PWC (p < 0.05) were identified, and decreases in anxiety scores (p < 0.05) and depression scores (p < 0.01) were noted in group 1 patients compared to group 3 patients. Group 2 patients significantly improved Pimax and SPimax (both p < 0.05) only with respect to group 3 patients. No significant differences were observed in group 3 patients.\n An 8-week program of high-intensity IMT resulted in significant benefits for CF patients, which included increased IMF and thickness of the diaphragm (during contraction), improved lung volumes, increased PWC, and improved psychosocial status.",
"Positive results from early clinical intervention of mild traumatic brain injury (MTBI) patients by rehabilitation specialists have been reported. Various treatments have been used, but few controlled studies are published. We hypothesised that early rehabilitation of selected MTBI patients would reduce long term sequelae.\n A randomised controlled trial with one year follow-up. Among 1719 consecutive patients with MTBI, 395 individuals, 16-60 years of age, met the MTBI definition. Exclusion criteria were: previous clinically significant brain disorders and/or a history of substance abuse. The control group (n = 131) received regular care. The intervention group (n = 264) was examined by a rehabilitation specialist. 78 patients were mainly referred to an occupational therapist. The problems were identified in daily activities and in terms of post-concussion symptoms (PCS), an individualised, tailored treatment was given. Primary endpoint was change in rate of PCS and in life satisfaction at one-year follow-up between the groups.\n No statistical differences were found between the intervention and control groups. Patients who experienced few PCS two to eight weeks after the injury and declined rehabilitation recovered and returned to their pre-injury status. Patients who suffered several PCS and accepted rehabilitation did not recover after one year.\n In this particular MTBI sample, early active rehabilitation did not change the outcome to a statistically-significant degree. Further studies should focus on patients with several complaints during the first 1-3 months and test various types of interventions.",
"To examine the impact of fitness training with recently brain-injured inpatients on exercise capacity and functional and psychologic outcome measures.\n A randomized controlled trial of exercise versus relaxation training for 3 months. Blind assessments were conducted before and after the end of a 12-week training program, as well as at follow-up assessment 12 weeks posttraining.\n Four regional neurologic inpatient rehabilitation units.\n Of 157 patients recruited 24 +/- 14 weeks after single-incident brain injury, 142 patients were assessed at week 12, and 128 patients at follow-up.\n Patients were randomized between cycle ergometer aerobic training and a relaxation training control condition, which was theoretically inert with respect to cardiovascular fitness.\n Validation of exercise training (peak work rate, peak heart rate, body mass index); mobility and physical function (modified Ashworth scale, Berg balance scale, Rivermead Mobility Index, 10-m walk velocity); disability and dependency (Barthel index, FIMtrade mark instrument, Nottingham Extended Activities of Daily Living); and psychologic function (fatigue questionnaire, Hospital Anxiety and Depression Scale).\n Significant improvements in exercise capacity (p <.05) in the exercise training group (n = 70) relative to the control group (n = 72) were not matched by greater improvements in functional independence, mobility, or psychologic function, at either 12 weeks or follow-up.\n The benefits of improved cardiovascular fitness did not appear to extend to measurable change in function or psychologic state.",
"The aim of this study was to assess the effects of cold-water immersion (cryotherapy) on indices of muscle damage following a bout of prolonged intermittent exercise. Twenty males (mean age 22.3 years, s = 3.3; height 1.80 m, s = 0.05; body mass 83.7 kg, s = 11.9) completed a 90-min intermittent shuttle run previously shown to result in marked muscle damage and soreness. After exercise, participants were randomly assigned to either 10 min cold-water immersion (mean 10 degrees C, s = 0.5) or a non-immersion control group. Ratings of perceived soreness, changes in muscular function and efflux of intracellular proteins were monitored before exercise, during treatment, and at regular intervals up to 7 days post-exercise. Exercise resulted in severe muscle soreness, temporary muscular dysfunction, and elevated serum markers of muscle damage, all peaking within 48 h after exercise. Cryotherapy administered immediately after exercise reduced muscle soreness at 1, 24, and 48 h (P < 0.05). Decrements in isometric maximal voluntary contraction of the knee flexors were reduced after cryotherapy treatment at 24 (mean 12%, s(x) = 4) and 48 h (mean 3%, s(x) = 3) compared with the control group (mean 21%, s(x) = 5 and mean 14%, s(x) = 5 respectively; P < 0.05). Exercise-induced increases in serum myoglobin concentration and creatine kinase activity peaked at 1 and 24 h, respectively (P < 0.05). Cryotherapy had no effect on the creatine kinase response, but reduced myoglobin 1 h after exercise (P < 0.05). The results suggest that cold-water immersion immediately after prolonged intermittent shuttle running reduces some indices of exercise-induced muscle damage.",
"Falls, loss of health-related quality of life and physical capacity, reduced participation in activities of daily living, and increased fear of falling are all potential outcomes for older adults discharged from hospital. A low-cost video based exercise programme may address this.\n This study was a randomized controlled trial with blinded outcomes assessment and a six-month follow-up.\n Participants were older adults (>65 years) using a mobility aid discharged from a tertiary hospital in Brisbane, Australia, without referral for community-based rehabilitation services.\n A digital video disk-based programme encompassing six exercise types each with six levels of difficulty. A home visit from a project physiotherapist was conducted to ensure patient safety. Control group patients received usual care.\n Falls, health-related quality of life, participation in activities of daily living, physical capacity and fear of falling.\n Study participants (n = 53, 19 intervention, 34 control) experienced decreasing health-related quality of life, several falls (72), and lower levels of participation in activities of daily living over the six-month follow-up. The intervention group did not differ significantly from the control group in terms of the outcomes examined, though a non-significant reduction in the rate of falls was observed. Intervention group participants complied with the exercise programme well during the first two weeks following discharge from hospital but then reduced their compliance levels thereafter.\n The intervention may be beneficial for reducing the rate of falls in this patient population though further research with a larger sample size is indicated."
] |
Overall, the evidence base for the effectiveness of interventions to reduce soft-tissue injury after intensive running is very weak, with few trials at low risk of bias. More well-designed and reported RCTs are needed that test interventions in recreational and competitive runners.
|
CD003085
|
[
"12414200",
"11022066"
] |
[
"International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial.",
"Outcomes of early endovascular versus surgical treatment of ruptured cerebral aneurysms. A prospective randomized study."
] |
[
"Endovascular detachable coil treatment is being increasingly used as an alternative to craniotomy and clipping for some ruptured intracranial aneurysms, although the relative benefits of these two approaches have yet to be established. We undertook a randomised, multicentre trial to compare the safety and efficacy of endovascular coiling with standard neurosurgical clipping for such aneurysms judged to be suitable for both treatments.\n We enrolled 2143 patients with ruptured intracranial aneurysms and randomly assigned them to neurosurgical clipping (n=1070) or endovascular treatment by detachable platinum coils (n=1073). Clinical outcomes were assessed at 2 months and at 1 year with interim ascertainment of rebleeds and death. The primary outcome was the proportion of patients with a modified Rankin scale score of 3-6 (dependency or death) at 1 year. Trial recruitment was stopped by the steering committee after a planned interim analysis. Analysis was per protocol.\n 190 of 801 (23.7%) patients allocated endovascular treatment were dependent or dead at 1 year compared with 243 of 793 (30.6%) allocated neurosurgical treatment (p=0.0019). The relative and absolute risk reductions in dependency or death after allocation to an endovascular versus neurosurgical treatment were 22.6% (95% CI 8.9-34.2) and 6.9% (2.5-11.3), respectively. The risk of rebleeding from the ruptured aneurysm after 1 year was two per 1276 and zero per 1081 patient-years for patients allocated endovascular and neurosurgical treatment, respectively.\n In patients with a ruptured intracranial aneurysm, for which endovascular coiling and neurosurgical clipping are therapeutic options, the outcome in terms of survival free of disability at 1 year is significantly better with endovascular coiling. The data available to date suggest that the long-term risks of further bleeding from the treated aneurysm are low with either therapy, although somewhat more frequent with endovascular coiling.",
"This prospective study was conducted to compare the outcomes of surgical clipping and endovascular treatment in acute (<72 hours) aneurysmal subarachnoid hemorrhage (SAH).\n One hundred nine consecutive patients were randomly assigned to either surgical (n=57) or endovascular (n=52) treatment. Clinical and neuropsychological outcome was assessed at 3 and 12 months after treatment; MRI of the brain was performed at 12 months. Follow-up angiography was scheduled after clipping and 3 and 12 months after endovascular treatment.\n One year postoperatively, 43/41 (surgical/endovascular) patients had good or moderate recovery, 5/4 had severe disability or were in a vegetative state, and 9/7 had died (NS) according to intention to treat. Patients with good clinical recovery did not differ in their neuropsychological test scores. Symptomatic vasospasm (OR 2.47; 95% CI 1.45 to 4.19; P<0.001), poorer Hunt and Hess grade (OR 2.50; 95% CI 1.31 to 4.75; P=0.005), need for permanent shunt (OR 8.90; 95% CI 1.80 to 44.15; P=0.008), and larger size of the aneurysm (OR 1. 22; 95% CI 1.02 to 1.45; P=0.032) independently predicted worsened clinical outcome regardless of the treatment modality. In MRI, superficial brain retraction deficits (P<0.001) and ischemic lesions in the territory of the ruptured aneurysm (P=0.025) were more frequent in the surgical group. Kaplan-Meier analysis (mean+/-SD follow-up 39+/-18 months) revealed equal survival in both treatment groups. No late rebleedings have occurred.\n One-year clinical and neuropsychological outcomes seem comparable after early surgical and endovascular treatment of ruptured intracranial aneurysms. The long-term efficacy of endovascular treatment in preventing rebleeding remains open."
] |
The evidence comes mainly from one large trial. For patients in good clinical condition with ruptured aneurysms of either the anterior or posterior circulation we have firm evidence that, if the aneurysm is considered suitable for both surgical clipping and endovascular treatment, coiling is associated with a better outcome.
|
CD004778
|
[
"19430829",
"11882751",
"8757375"
] |
[
"Randomized clinical trial of laparoscopic versus open repair of the perforated peptic ulcer: the LAMA Trial.",
"Laparoscopic repair for perforated peptic ulcer: a randomized controlled trial.",
"A randomized study comparing laparoscopic versus open repair of perforated peptic ulcer using suture or sutureless technique."
] |
[
"Laparoscopic surgery has become popular during the last decade, mainly because it is associated with fewer postoperative complications than the conventional open approach. It remains unclear, however, if this benefit is observed after laparoscopic correction of perforated peptic ulcer (PPU). The goal of the present study was to evaluate whether laparoscopic closure of a PPU is as safe as conventional open correction.\n The study was based on a randomized controlled trial in which nine medical centers from the Netherlands participated. A total of 109 patients with symptoms of PPU and evidence of air under the diaphragm were scheduled to receive a PPU repair. After exclusion of 8 patients during the operation, outcomes were analyzed for laparotomy (n = 49) and for the laparoscopic procedure (n = 52).\n Operating time in the laparoscopy group was significantly longer than in the open group (75 min versus 50 min). Differences regarding postoperative dosage of opiates and the visual analog scale (VAS) for pain scoring system were in favor of the laparoscopic procedure. The VAS score on postoperative days 1, 3, and 7 was significant lower (P < 0.05) in the laparoscopic group. Complications were equally distributed. Hospital stay was also comparable: 6.5 days in the laparoscopic group versus 8.0 days in the open group (P = 0.235).\n Laparoscopic repair of PPU is a safe procedure compared with open repair. The results considering postoperative pain favor the laparoscopic procedure.",
"To compare the results of open versus laparoscopic repair for perforated peptic ulcers.\n Omental patch repair with peritoneal lavage is the mainstay of treatment for perforated peptic ulcers in many institutions. Laparoscopic repair has been used to treat perforated peptic ulcers since 1990, but few randomized studies have been carried out to compare open versus laparoscopic procedures.\n From January 1994 to June 1997, 130 patients with a clinical diagnosis of perforated peptic ulcer were randomly assigned to undergo either open or laparoscopic omental patch repair. Patients were excluded for a history of upper abdominal surgery, concomitant evidence of bleeding from the ulcer, or gastric outlet obstruction. Patients with clinically sealed-off perforations without signs of peritonitis or sepsis were treated without surgery. Laparoscopic repair would be converted to an open procedure for technical difficulties, nonjuxtapyloric gastric ulcers, or perforations larger than 10 mm. A Gastrografin meal was performed 48 to 72 hours after surgery to document sealing of the perforation. The primary end-point was perioperative parenteral analgesic requirement. Secondary endpoints were operative time, postoperative pain score, length of postoperative hospital stay, complications and deaths, and the date of return to normal daily activities.\n Nine patients with a surgical diagnosis other than perforated peptic ulcer were excluded; 121 patients entered the final analysis. There were 98 male and 23 female patients recruited, ages 16 to 89 years. The two groups were comparable in age, sex, site and size of perforations, and American Society of Anesthesiology classification. There were nine conversions in the laparoscopic group. After surgery, patients in the laparoscopic group required significantly less parenteral analgesics than those who underwent open repair, and the visual analog pain scores in days 1 and 3 after surgery were significantly lower in the laparoscopic group as well. Laparoscopic repair required significantly less time to complete than open repair. The median postoperative stay was 6 days in the laparoscopic group versus 7 days in the open group. There were fewer chest infections in the laparoscopic group. There were two intraabdominal collections in the laparoscopic group. One patient in the laparoscopic group and three patients in the open group died after surgery.\n Laparoscopic repair of perforated peptic ulcer is a safe and reliable procedure. It was associated with a shorter operating time, less postoperative pain, reduced chest complications, a shorter postoperative hospital stay, and earlier return to normal daily activities than the conventional open repair.",
"This study compares laparoscopic versus open repair and suture versus sutureless repair of perforated duodenal and juxtapyloric ulcers.\n The place of laparoscopic repair of perforated peptic ulcer followed by peritoneal toilet of the peritoneal cavity has been established. Whether repair of the perforated peptic ulcer by the laparoscopic approach is better than conventional open repair and whether sutured repair is better than sutureless repair are both undetermined.\n One hundred three patients were randomly allocated to laparoscopic suture repair, laparoscopic sutureless repair, open suture repair, and open sutureless repair.\n Laparoscopic repair of perforated peptic ulcer (groups 1 and 2) took significantly longer than open repair (groups 3 and 4; 94.3 +/ 40.3 vs. 53.7 +/ 42.6 minutes: Student's test, p < 0.001), but the amount of analgesic required after laparoscopic repair was significantly less than in open surgery (median 1 dose vs. 3 doses) (Mann-Whitney U test, p = 0.03). There was no significant difference in the four groups of patients in terms of duration of nasogastric aspiration, duration of intravenous drip, total hospital stay, time to resume normal diet, visual analogue scale score for pain in the first 24 hours after surgery, morbidity, reoperation, and mortality rates.\n Laparoscopic repair of perforated peptic ulcer is a viable option. Sutureless repair is as safe as suture repair and it takes less time to perform."
] |
This review suggests that a decrease in septic abdominal complications may exist when laparoscopic surgery is used to correct perforated peptic ulcer. However, it is necessary to perform more randomized controlled trials with a greater number of patients to confirm such an assumption, guaranteeing a long learning curve for participating surgeons. With the information provided it could be said that laparoscopic surgery results are not clinically different from those of open surgery.
|
CD000323
|
[
"16708735",
"16361020",
"20667840",
"15733717",
"9739036",
"21290830",
"20138037",
"16544087",
"21441148",
"8555849",
"1628013",
"19229451",
"1456568",
"15684319",
"9351723",
"1298056",
"17214109",
"15920748"
] |
[
"A prospective comparison of percutaneous endoscopic gastrostomy and nasogastric tube feeding in patients with acute dysphagic stroke.",
"Behavioural intervention for dysphagia in acute stroke: a randomised controlled trial.",
"Does looped nasogastric tube feeding improve nutritional delivery for patients with dysphagia after acute stroke? A randomised controlled trial.",
"Effect of timing and method of enteral tube feeding for dysphagic stroke patients (FOOD): a multicentre randomised controlled trial.",
"A randomized, controlled, a single-blind trial of nutritional supplementation after acute stroke.",
"[Dysphagia after stroke treated with acupuncture or electric stimulation: a randomized controlled trial].",
"Adjunctive functional pharyngeal electrical stimulation reverses swallowing disability after brain lesions.",
"Evaluating oral stimulation as a treatment for dysphagia after stroke.",
"Noninvasive brain stimulation may improve stroke-related dysphagia: a pilot study.",
"A randomised prospective comparison of percutaneous endoscopic gastrostomy and nasogastric tube feeding after acute dysphagic stroke.",
"Randomised comparison of percutaneous endoscopic gastrostomy and nasogastric tube feeding in patients with persisting neurological dysphagia.",
"Neuromuscular electrical and thermal-tactile stimulation for dysphagia caused by stroke: a randomized controlled trial.",
"Physiologic effects of oral supplemental feeding in malnourished patients with chronic obstructive pulmonary disease. A randomized control study.",
"Dietary counseling improves patient outcomes: a prospective, randomized, controlled trial in colorectal cancer patients undergoing radiotherapy.",
"A prospective, randomized trial of early enteral feeding after resection of upper gastrointestinal malignancy.",
"Feeding via nasogastric tube or percutaneous endoscopic gastrostomy. A comparison.",
"Tube feeding in the demented elderly with severe disabilities.",
"Impact of nutrition on outcome: a prospective randomized controlled trial in patients with head and neck cancer undergoing radiotherapy."
] |
[
"Dysphagia following stroke is common problem and is of particular concern because of its potental for malnutrition. Nasogastric (NG) and percutaneous endoscopic gastrostomy (PEG) tube feeding are recognized methods for nutritional support for patients with persistent neurologic dysphagia. However, the former is associated with tube dislodgement and blockage that might compromise the patients' nutritional status. There have been few randomized prospective studies to date comparing the efficacy and safety of these 2 modes of dysphagia management in stroke patients. The objective of this study was to compare PEG with NG tube feeding after acute dysphagic stroke in terms of nutritional status and treatment failure. This was a randomized prospective clinical trial. A total of 23 consecutive patients who fulfilled the criteria were recruited from the medical wards in Hospital Universiti Kebangsaan Malaysia. The diagnosis of stroke (acute cerebral infarct) was based on clinical and brain computed tomographic (CT scan) findings; and the diagnosis of dysphagia was done clinically by using the 'swallowing test'. At recruitment, upper-arm skin fold thickness (triceps and biceps) and mid-arm circumference were measured; and blood was drawn for serum albumin level. They were then followed up at 4 weeks where the above tests were repeated. A total of 22 patients completed the study (12 patients in the NG group and 10 patients in the PEG group). Serum albumin levels (p = 0.045) were significantly higher in the PEG as compared to the NG group at 4 weeks post-intervention. There were statistically significant improvements in serum albumin level (p = 0.024) in the PEG group; and statistically significant reductions in serum albumin level (p = 0.047) in the NG group 4 weeks after the intervention. However, there were no significant differences in anthropometric parameters between the two groups and no significant changes in these parameters for each group 4 weeks after the intervention. Treatment failure occurred in 5 out of 10 patients (50.0%) in the NG group, but none in PEG group (p = 0.036). PEG tube feeding is more effective than NG tube feeding in improving the nutritional status (in terms of the serum albumin level) of patients with dysphagic stroke. NG tube feeding, in fact, reduced the nutritional status (in terms of the serum albumin level) of the patients.",
"Swallowing dysfunction after stroke is common, but there is little reliable evidence for how the disorder should be managed. This study compared standard low-intensity and high-intensity behavioural interventions with usual care for dysphagia.\n 306 patients with clinical dysphagia admitted to hospital with acute stroke were randomly assigned to receive usual care (n=102), prescribed by the attending physician; standard low-intensity intervention (n=102), comprising swallowing compensation strategies and diet prescription three times weekly for up to a month; or standard high-intensity intervention and dietary prescription (n=102), at least daily for up to a month. The primary outcome measure was survival free of an abnormal diet at 6 months. Analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00257764.\n 60 patients died and three patients were lost to follow up before the 6-month analysis. Of patients randomly allocated usual care, 56% (57/102) survived at 6 months free of an abnormal diet compared with 67% (136/204) allocated standard swallowing therapy (relative risk 1.19, 95% CI 0.98-1.45). Standard swallowing therapy was associated with a non-significant trend toward a reduction in death (0.80, 0.5-1.3), institutionalisation (0.69, 0.4-1.1), and dependency (1.05, 0.8-1.3); a significant reduction in swallowing-related medical complications (0.73, 0.6-0.9), chest infection (0.56, 0.4-0.8), and death or institutionalisation (0.73, 0.55-0.97); and a significant rise in the proportion of patients regaining swallowing function (1.41, 1.03-1.94) by 6 months. Compared with usual care and low-intensity therapy, high-intensity therapy was associated with an increased proportion of patients who returned to a normal diet (p=0.04) and recovered swallowing (p=0.02) by 6 months.\n These data show a consistent trend towards more favourable outcomes in dysphagic stroke patients who are assigned a standard programme of early behavioural swallowing intervention, including active therapeutic approaches and dietary modification.",
"nasogastric tube (NGT) feeding is commonly used after stroke, but its effectiveness is limited by frequent dislodgement.\n the objective of the study was to evaluate looped NGT feeding in acute stroke patients with dysphagia.\n this was a randomised controlled trial of 104 patients with acute stroke fed by NGT in three UK stroke units. NGT was secured using either a nasal loop (n = 51) or a conventional adhesive dressing (n = 53). The main outcome measure was the proportion of prescribed feed and fluids delivered via NGT in 2 weeks post-randomisation. Secondary outcomes were frequency of NGT insertions, treatment failure, tolerability, adverse events and costs at 2 weeks; mortality; length of hospital stay; residential status; and Barthel Index at 3 months.\n participants assigned to looped NGT feeding received a mean 17% (95% confidence interval 5-28%) more volume of feed and fluids, required fewer NGTs (median 1 vs 4), and had fewer electrolyte abnormalities than controls. There was more minor nasal trauma in the loop group. There were no differences in outcomes at 3 months. Looped NGT feeding cost 88 pounds sterling more per patient over 2 weeks than controls.\n looped NGT feeding improves delivery of feed and fluids and reduces NGT reinsertion with little additional cost.",
"Undernutrition is common in patients admitted with stroke. We aimed to establish whether the timing and route of enteral tube feeding after stroke affected patients' outcomes at 6 months.\n The FOOD trials consist of three pragmatic multicentre randomised controlled trials, two of which included dysphagic stroke patients. In one trial, patients enrolled within 7 days of admission were randomly allocated to early enteral tube feeding or no tube feeding for more than 7 days (early versus avoid). In the other, patients were allocated percutaneous endoscopic gastrostomy (PEG) or nasogastric feeding. The primary outcome was death or poor outcome at 6 months. Analysis was by intention to treat.\n Between Nov 1, 1996, and July 31, 2003, 859 patients were enrolled by 83 hospitals in 15 countries into the early versus avoid trial. Early tube feeding was associated with an absolute reduction in risk of death of 5.8% (95% CI -0.8 to 12.5, p=0.09) and a reduction in death or poor outcome of 1.2% (-4.2 to 6.6, p=0.7). In the PEG versus nasogastric tube trial, 321 patients were enrolled by 47 hospitals in 11 countries. PEG feeding was associated with an absolute increase in risk of death of 1.0% (-10.0 to 11.9, p=0.9) and an increased risk of death or poor outcome of 7.8% (0.0 to 15.5, p=0.05).\n Early tube feeding might reduce case fatality, but at the expense of increasing the proportion surviving with poor outcome. Our data do not support a policy of early initiation of PEG feeding in dysphagic stroke patients.",
"Although stroke patients who do not have difficulty swallowing may be at risk of undernutrition and worsening nutritional status during hospitalization, optimum methods for nutrition intervention in stroke patients have not been established.\n To examine the feasibility of enteral sip feeding as an effective nutrition intervention after acute stroke.\n Forty-two acute ischemic stroke inpatients with impaired nutritional status who did not have difficulty swallowing within 1 week after the stroke were entered into a single-blind, randomized, controlled, prospective study of enteral sip feeding. Twenty-one patients were randomized to receive daily oral food supplements for 4 weeks in addition to the hospital food, and 21 patients received only the hospital food for the same period. Main outcome measures were energy and protein intakes during the intervention period, change in nutritional status, disability, infective complications, length of stay, and mortality during hospitalization and at 3 months.\n Two patients, one from each group, were lost to follow-up immediately after randomization. Twenty patients received oral nutritional supplementation. The energy intake was significantly greater in the supplemented group: 1807 +/- 318 vs 1084 +/- 343 kcal/d (mean +/- SD; p < .0001) (estimated treatment effect, 723 kcal/d; 95% confidence interval [CI], 498 to 947), as was protein intake: 65.1 +/- 13.8 vs 44.1 +/- 12.8 g/d (p < .001) (estimated treatment effect, 21.0 g/d; 95% CI, 11.7 to 30.3). There also were significant differences between the two groups in the changes in serum albumin and serum iron concentrations between randomization and at follow-up. There was a trend to lower mortality at 3 months in the supplemented group with two deaths (10%) compared with seven deaths (35%) in the control group (p = .127, relative risk, 0.29; 95% CI, 0.07 to 1.21).\n This study suggests that enteral sip feeding is effective in improving nutritional intake and status in stroke patients who do not have swallowing difficulties. There also may be some beneficial effects on clinical outcome, but larger studies are required to confirm this observation and define more precisely the magnitude of any favorable effects.",
"To compare the therapeutic effects between acupuncture and electric stimulation on post-stroke dysphagia on the basis of rehabilitation training.\n Ninety-seven patients with post-stroke dysphagia were randomly divided into an acupuncture group (group A, n = 32), an electric stimulation group (group B, n = 35) and a rehabilitation training group (group C, n = 30). In group C, the conventional therapy (conventional therapy of neurologic internal medicine and rehabilitation training) was applied. In group A, the combination of conventional therapy and acupuncture was applied. The acupoints of Fengchi (GB 20), Futu (LI 18), three-needles on the forehead, etc. were selected. In group B, the combination of conventional therapy and electric stimulation was adopted. Watian drinking water experiment, stethocatharsis function scoring and video fluoroscopic swallowing study (VFSS) were used to evaluate swallowing function of patients.\n After treatment, the total effective rate was 96.95 (31/32) in group A and was 94.3% (33/35) in group B, which was superior to that of 66.7% (20/30) in group C (P < 0.01). After treatment, the swallowing function in group A, group B and group C were all improved significantly as compared with that before treatment (all P < 0.05). After treatment, the effects in group A and B were superior to that in group C (both P < 0.05).\n The therapeutic effect of the combination of either acupuncture or electric stimulation with rehabilitation training is better than that of simple rehabilitation training. The efficacy on dysphagia is equal between acupuncture and electric stimulation.",
"Oropharyngeal dysphagia is an important disability that occurs after stroke; it contributes to aspiration pneumonia and death, and current modalities for rehabilitation of dysphagia have uncertain efficacy. We therefore examined the role of pharyngeal electrical stimulation (PES) in expediting human swallowing recovery after experimental (virtual) and actual (stroke) brain lesions.\n First, healthy subjects (n = 13) were given 1-Hz repetitive transcranial magnetic stimulation to induce a unilateral virtual lesion in pharyngeal motor cortex followed by active or sham (control) PES. Motor-evoked potentials and swallow accuracy were recorded before and after the lesion to assess PES response. Thereafter, 50 acute dysphagic stroke patients underwent either a dose-response study, to determine optimal parameters for PES (n = 22), or were assigned randomly to groups given either active or sham (control) PES (n = 28). The primary end point was the reduction of airway aspiration at 2 weeks postintervention.\n In contrast to sham PES, active PES reversed the cortical suppression induced by the virtual lesion (F(7,70) = 2.7; P = .015) and was associated with improvement in swallowing behavior (F(3,42) = 5; P = .02). After stroke, 1 PES treatment each day (U = 8.0; P = .043) for 3 days (U = 10.0) produced improved airway protection compared with controls (P = .038). Active PES also reduced aspiration (U = 54.0; P = .049), improved feeding status (U = 58.0; P = .040), and resulted in a shorter time to hospital discharge (Mantel-Cox log-rank test, P = 0.038).\n This pilot study of PES confirms that it is a safe neurostimulation intervention that reverses swallowing disability after virtual lesion or stroke.\n Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.",
"Deglutitive aspiration is common after stroke and can have devastating consequences. While the application of oral sensory stimulation as a treatment for dysphagia remains controversial, data from our laboratory have suggested that it may increase corticobulbar excitability, which in previous work was correlated with swallowing recovery after stroke. Our study assessed the effects of oral stimulation at the faucial pillar on measures of swallowing and aspiration in patients with dysphagic stroke. Swallowing was assessed before and 60 min after 0.2-Hz electrical or sham stimulation in 16 stroke patients (12 male, mean age = 73 +/- 12 years). Swallowing measures included laryngeal closure (initiation and duration) and pharyngeal transit time, taken from digitally acquired videofluoroscopy. Aspiration severity was assessed using a validated penetration-aspiration scale. Preintervention, the initiation of laryngeal closure, was delayed in both groups, occurring 0.66 +/- 0.17 s after the bolus arrived at the hypopharynx. The larynx was closed for 0.79 +/- 0.07 s and pharyngeal transit time was 0.94 +/- 0.06 s. Baseline swallowing measures and aspiration severity were similar between groups (stimulation: 24.9 +/- 3.01; sham: 24.9 +/- 3.3, p = 0.2). Compared with baseline, no change was observed in the speed of laryngeal elevation, pharyngeal transit time, or aspiration severity within subjects or between groups for either active or sham stimulation. Our study found no evidence for functional change in swallow physiology after faucial pillar stimulation in dysphagic stroke. Therefore, with the parameters used in this study, oral stimulation does not offer an effective treatment for poststroke patients.",
"Treatment options for stroke-related dysphagia are currently limited. In this study, we investigated whether noninvasive brain stimulation in combination with swallowing maneuvers facilitates swallowing recovery in dysphagic stroke patients during early stroke convalescence.\n Fourteen patients with subacute unilateral hemispheric infarction were randomized to anodal transcranial direct current stimulation (tDCS) versus sham stimulation to the sensorimotor cortical representation of swallowing in the unaffected hemisphere over the course of 5 consecutive days with concurrent standardized swallowing maneuvers. Severity of dysphagia was measured using a validated swallowing scale, Dysphagia Outcome and Severity scale, before the first and after the last session of tDCS or sham. The effect of tDCS was analyzed in a multivariate linear regression model using changes in Dysphagia Outcome and Severity Scale as the outcome variable after adjusting for the effects of other potential confounding variables such as the National Institutes of Health Stroke Scale and Dysphagia Outcome and Severity scale scores at baseline, acute ischemic lesion volumes, patient age, and time from stroke onset to stimulation.\n Patients who received anodal tDCS gained 2.60 points of improvement in Dysphagia Outcome and Severity scale scores compared to patients in the sham stimulation group who showed an improvement of 1.25 points (P=0.019) after controlling for the effects of other aforementioned variables. Six out 7 (86%) patients in tDCS stimulation group gained at least 2 points of improvement compared with 3 out 7 (43%) patients in the sham group (P=0.107).\n Because brain stem swallowing centers have bilateral cortical innervations, measures that enhance cortical input and sensorimotor control of brain stem swallowing may be beneficial for dysphagia recovery.",
"To compare percutaneous endoscopic gastrostomy and nasogastric tube feeding after acute dysphagic stroke.\n Randomised prospective study of inpatients with acute stroke requiring enteral nutrition.\n One university hospital (Nottingham) and one district general hospital (Derby).\n 30 patients with persisting dysphagia at 14 days after acute stroke: 16 patients were randomised to gastrostomy tube feeding and 14 to nasogastric tube feeding.\n Six week mortality; amount of feed administered; change in nutritional state; treatment failure; and length of hospital stay.\n Mortality at 6 weeks was significantly lower in the gastrostomy group with two deaths (12%) compared with eight deaths (57%) in the nasogastric group (P < 0.05). All gastrostomy fed patients (16) received the total prescribed feed whereas 10/14 (71%) of nasogastric patients lost at least one day's feed. Nasogastric patients received a significantly (P < 0.001) smaller proportion of their prescribed feed (78%; 95% confidence interval 63% to 94%) compared with the gastrostomy group (100%). Patients fed via a gastrostomy tube showed greater improvement in nutritional state, according to several different criteria at six weeks compared with the nasogastric group. In the gastrostomy group the mean albumin concentration increased from 27.1 g/l (24.5 g/l to 29.7 g/l) to 30.1 g/l (28.3 g/l to 31.9 g/l). In contrast, among the nasogastric group there was a reduction from 31.4 g/l (28.6 g/l to 34.2 g/l) to 22.3 g/l (20.7 g/l to 23.9 g/l) (P < 0.003). In addition, there were fewer treatment failures in the gastrostomy group (0/16 versus 3/14). Six patients from the gastrostomy group were discharged from hospital within six weeks of the procedure compared with none from the nasogastric group (P < 0.05).\n This study indicates that early gastrostomy tube feeding is greatly superior to nasogastric tube feeding and should be the nutritional treatment of choice for patients with acute dysphagic stroke.",
"To compare percutaneous endoscopic gastrostomy and nasogastric tube feeding in patients with persisting neurological dysphagia.\n Randomised 28 day study of inpatients requiring long term enteral nutrition.\n Three Glasgow teaching hospitals.\n 40 patients with dysphagia for at least four weeks secondary to neurological disorders: 20 patients (10 women) were randomised to nasogastric feeding and 20 (eight women) to endoscopic gastrostomy.\n Treatment failure (blocked or displaced tubes on three or more occasions or refusal to continue treatment); duration of feeding; intake of liquid diets; complications; nutritional status at end of trial.\n One patient in each group died before starting feeding. Treatment failure occurred in 18 of the 19 nasogastric patients and in none of the gastrostomy group. The mean (SE) duration of feeding for the nasogastric group was 5.2 (1.5) days. No complications occurred in the nasogastric group but three (16%) of the gastrostomy group developed minor problems (aspiration pneumonia (two patients) wound infection (one)). Gastrostomy patients received a significantly greater proportion of their prescribed feed (93% (2%)) compared with the nasogastric group, (55% (4%); p less than 0.001) and also gained significantly more weight after seven days of feeding (1.4 (0.5) kg v 0.6 (0.1) kg; p less than 0.05). Analyses at days 14, 21, and 28 were not possible due to the small numbers remaining in the nasogastric group.\n Percutaneous endoscopic gastrostomy tube feeding is a safe and effective method of providing long term enteral nutrition to patients with neurological dysphagia and offers important advantages over nasogastric tube feeding.",
"The aim of this study was to assess the effectiveness of neuromuscular electrical stimulation in patients with dysphagia caused by stroke.\n Thirty-six subjects were randomized into experimental and control groups. The control group was given thermal-tactile stimulation treatment only, while in the experimental group neuromuscular electrical stimulation and thermal-tactile stimulation treatments were applied simultaneously. Swallowing function was assessed before and 4 weeks after treatment, and evaluated via the swallow function scoring system, penetration-aspiration scale, and pharyngeal transit time. In addition, the discomfort score during the treatments and the satisfaction score 4 weeks after the treatments were measured.\n Twenty-eight persons with dysphagia completed the study, 16 in the experimental group and 12 in the control group. Both groups showed improvement, but the experimental group showed more significant improvement in the swallow function scoring system, penetration-aspiration scale and pharyngeal transit time than the control group. The patient's discomfort score did not show statistically significant differences in either group, but the satisfactory score was higher in the experimental group.\n The results suggest that neuromuscular electrical stimulation combined with thermal-tactile stimulation is a better treatment for patients with swallowing disorders after stroke than thermal-tactile stimulation alone.",
"The association between severe nutritional depletion and chronic obstructive pulmonary disease (COPD) has long been recognized. A potential therapeutic benefit to nutritional support was previously suggested by us in a pilot investigation. Subsequent studies have reported conflicting results regarding the role of nutritional therapy in this clinical population. We report a randomized controlled study of nutritional therapy in underweight patients with COPD that combines an initial inpatient investigation (controlled nutritional support) with a prolonged outpatient follow-up interval. Provision of adequate calorie and protein support, adjusted to metabolic requirements, resulted in weight gain (intervention = +2.4 kg versus control -0.5 kg), improved handgrip strength (intervention = +5.5 kg-force versus control -6.0 kg-force), expiratory muscle strength (intervention = +14.9 cm H2O versus control -9.2 cm H2O), and walking distance (intervention = +429 feet versus control -1.0 foot). Inspiratory muscle strength was also improved (intervention = +11.4 cm H2O versus control +4.8 cm H2O) although this did not quite reach statistical significance. We conclude that provision of adequate nutrient supply under controlled conditions results in significant clinical improvements in the COPD patient population. However, the intervention is costly, time-intensive, and of limited therapeutic magnitude. More detailed work of alternative outpatient strategies combined with additional rehabilitative measures is indicated to delineate the full therapeutic potential of nutritional support for this clinical population.",
"To investigate the impact of dietary counseling or nutritional supplements on outcomes in cancer patients: nutritional, morbidity, and quality of life (QoL) during and 3 months after radiotherapy.\n A total of 111 colorectal cancer outpatients referred for radiotherapy, stratified by staging, were randomly assigned: group 1 (G1; n = 37), dietary counseling (regular foods); group 2 (G2; n = 37), protein supplements; and group 3 (G3; n = 37), ad libitum intake. Nutritional intake (diet history), status (Ottery's Subjective Global Assessment), and QoL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire version 3.0) were evaluated at baseline, at the end, and 3 months after radiotherapy.\n At radiotherapy completion, energy intake increased in G1/G2 (P < or = .04), G1 more than G2 (P = .001), and decreased in G3 (P < .01). Protein intake increased in G1/G2 (P < or = .007), G1 less than G2 (not significant), and decreased in G3 (P < .01). At 3 months, G1 maintained nutritional intake and G2/G3 returned to baseline. After radiotherapy and at 3 months, rates of anorexia, nausea, vomiting, and diarrhea were higher in G3 (P < .05). At radiotherapy completion, in G1 all QoL function scores improved proportionally to adequate intake or nutritional status (P < .05); whereas in G2 only three of six function scores improved proportionally to protein intake (P = .04), and in G3 all scores worsened (P < .05). At 3 months, G1 patients maintained/improved function, symptoms, and single-item scores (P < .02); in G2, only few function and symptom scales improved (P < .05); in G3, QoL remained as poor as after radiotherapy. In G1/G2, respectively, improvement/deterioration of QoL correlated with better or poorer intake or nutritional status (P < .003).\n During radiotherapy, both interventions positively influenced outcomes; dietary counseling was of similar or higher benefit, whereas even 3 months after RT, it was the only method to sustain a significant impact on patient outcomes.",
"The purpose of the study was to determine whether early postoperative enteral feeding with an immune-enhancing formula (IEF) decreases morbidity, mortality, and length of hospital stay in patients with upper gastrointestinal (GI) cancer.\n Early enteral feeding with an IEF has been associated with improved outcome in trauma and critical care patients. Evaluable data documenting reduced complications after major upper GI surgery for malignancy with early enteral feeding are limited.\n Between March 1994 and August 1996, 195 patients with a preoperative diagnosis of esophageal (n = 23), gastric (n = 75), peripancreatic (n = 86), or bile duct (n = 11) cancer underwent resection and were randomized to IEF via jejunostomy tube or control (CNTL). Tube feedings were supplemented with arginine, RNA, and omega-3 fatty acids, begun on postoperative 1, and advanced to a goal of 25 kcal/kg per day. The CNTL involved intravenous crystalloid solutions. Statistical analysis was by t test, chi square, or logistic regression.\n Patient demographics, nutritional status, and operative factors were similar between the groups. Caloric intake was 61% and 22% of goal for the IEF and CNTL groups, respectively. The IEF group received significantly more protein, carbohydrate, lipids and immune-enhancing nutrients than did the CNTL group. There were no significant differences in the number of minor, major, or infectious wound complications between the groups. There was one bowel necrosis associated with IEF requiring reoperation. Hospital mortality was 2.5% and median length of hospital stay was 11 days, which was not different between the groups.\n Early enteral feeding with an IEF was not beneficial and should not be used in a routine fashion after surgery for upper GI malignancies.",
"When a patient needs enteral feeding, there are two methods to administer the nutrition. The method most used is the nasogastric tube (NGT), although in the literature little is published about the advantages and complications of the NGT. The second method is percutaneous endoscopic gastrostomy (PEG). A prospective randomized trial was started, and so far 90 patients have entered the study (46 NGT and 44 PEG). In four patients it was not possible to insert the NGT, and in three patients it was impossible to place the PEG. In both groups 6.5% aspiration was found. Nasal decubitus and swallowing problems were seen in 13% and 17%, respectively, in the NGT group. Intraperitoneal bleeding and abdominal pain were found in 2% and 11%, respectively, in the PEG group. Fixation of the patients was needed in 7% of the PEG and 22% in the NGT group. In eight patients in the NGT group the feeding had to be stopped owing to problems; in none of the PEG group was this necessary. The nursing staff awarded marks to each patient on a scale of 5 for the convenience of care (very good, 1; very bad, 5). This resulted in a mean score of 2.6 in the NGT and 2.0 in the PEG group. The score given by the patients was 2.3 in the NGT and 1.8 in the PEG group. There seems to be a clear preference for the PEG as a method for enteral nutrition.",
"Despite the ongoing debate on tube feeding of severely demented patients, the current approach in western countries is to avoid feeding by tube.\n To assess the clinical course and outcome of demented elderly patients with severe disabilities, by feeding mode.\n The study was conducted in a skilled nursing department of a major psychogeriatric hospital in Israel. Eighty-eight patients aged 79 +/- 9 years were followed for 17 months: 62 were fed by nasogastric tube and 26 were orally fed. The groups were compared for background characteristics, underlying medical condition, functional impairment, clinical and nutritional outcomes, and survival.\n Tube feeding had no beneficial effect on clinical and nutritional outcomes or on healing preexisting pressure ulcers, compared with oral feeding. Very few patients on tube feeding showed signs of discomfort, partly because of low cognitive function. Survival was significantly higher in the tube-fed patients (P < 0.001), which could be partly explain by the different case mix (i.e., the underlying diseases)\n Tube feeding seems to have no nutritional advantage in severely demented elderly patients. Median survival was longer in tube-fed individuals who had no acute co-morbidity. However, since tube feeding does not add to patient pain and discomfort, it should not be contraindicated when it complies with the values and wishes of patients and their families.",
"We aimed to determine the effect of dietary counseling or oral supplements on outcome for patients with cancer, specifically, nutritional outcome, morbidity, and quality of life (QOL), during and 3 months after radiotherapy.\n Seventy-five patients with head and neck cancer who were referred for radiotherapy (RT) were randomized to the following groups: group 1 (n = 25), patients who received dietary counseling with regular foods; group 2 (n = 25), patients who maintained usual diet plus supplements; and group 3 (n = 25), patients who maintained intake ad lib. Nutritional intake (determined by diet history) and status (determined by Ottery's Subjective Global Assessment), and QOL (determined by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire version 3.0 [EORTC QLQ-C30]) were evaluated at baseline, at the end of RT, and at 3 months.\n Energy intake after RT increased in both groups 1 and 2 (p < or = .05). Protein intake also increased in both groups 1 and 2 (p < or = .006). Both energy and protein intake decreased significantly in group 3 (p < .01). At 3 months, group 1 maintained intakes, whereas groups 2 and 3 returned to or below baseline levels. After RT, >90% of patients experienced RT toxicity; this was not significantly different between groups, with a trend for reduced symptomatology in group 1 versus group 2/group 3 (p < .07). At 3 months, the reduction of incidence/severity of grade 1+2 anorexia, nausea/vomiting, xerostomia, and dysgeusia was different: 90% of the patients improved in group 1 versus 67% in group 2 versus 51% in group 3 (p < .0001). After RT, QOL function scores improved (p < .003) proportionally with improved nutritional intake and status in group 1/group 2 (p < .05) and worsened in group 3 (p < .05); at 3 months, patients in group 1 maintained or improved overall QOL, whereas patients in groups 2 and 3 maintained or worsened overall QOL.\n During RT, nutritional interventions positively influenced outcomes, and counseling was of similar/higher benefit; in the medium term, only counseling exerted a significant impact on patient outcomes.\n Copyright 2005 Wiley Periodicals, Inc."
] |
There remains insufficient data on the effect of swallowing therapy, feeding, and nutritional and fluid supplementation on functional outcome and death in dysphagic patients with acute or subacute stroke. Behavioural interventions and acupuncture reduced dysphagia, and pharyngeal electrical stimulation reduced pharyngeal transit time. Compared with NGT feeding, PEG reduced treatment failures and gastrointestinal bleeding, and had higher feed delivery and albumin concentration. Nutritional supplementation was associated with reduced pressure sores, and increased energy and protein intake.
|
CD003535
|
[
"3530643",
"6219156",
"16387583",
"20001651",
"2874221",
"7439516",
"8121733",
"2879458"
] |
[
"Reduction of nocturnal asthma by an inhaled anticholinergic drug.",
"Anticholinergic and sympathomimetic combination therapy of asthma.",
"Response profiles to fluticasone and montelukast in mild-to-moderate persistent childhood asthma.",
"Predicting short term response to anti-inflammatory therapy in young children with asthma.",
"Family therapy in the treatment of severe childhood asthma.",
"A comparative trial of slow-release aminophylline, salbutamol and a half dose combination in the prevention of childhood asthma.",
"Aminophylline therapy does not improve outcome and increases adverse effects in children hospitalized with acute asthmatic exacerbations.",
"Nebulized anticholinergic and sympathomimetic treatment of asthma and chronic obstructive airways disease in the emergency room."
] |
[
"Although the mechanisms of nocturnal asthma are still uncertain, increased vagal cholinergic tone may be contributory factor. To examine this hypothesis, we have studied the effect of an anticholinergic drug, oxitropium bromide, on the early morning fall in peak expiratory flow (PEF) in patients with nocturnal asthma. Eighteen patients (aged 18 to 76 years; seven men) with documented nocturnal asthma were studied in a double-blind randomized cross-over study in which they received either oxitropium bromide (200 micrograms or 400 micrograms) or placebo in a single dose at night for two-week periods. With placebo the mean (+/- SE) fall in PEF (expressed as percentage of evening PEF) was 17.3 +/- 2.0 percent, which was significantly reduced to 10.3 +/- 3.3 percent after oxitropium (400 micrograms) (p less than 0.05; ANOVA). Closer analysis revealed that nine of the 18 patients had responded in a dose-dependent manner, with the mean percentage decreases with placebo, 200 micrograms, and 400 micrograms of oxitropium being 19.1 +/- 3.2, 11.5 +/- 4.4, and 5.0 +/- 4.5 percent, respectively (p less than 0.01 between each treatment). The remaining patients were unaffected by therapy. There were no differences between \"responders\" and \"non-responders\" in terms of age, atopic status, duration of asthma, severity of asthma, or bronchodilator response to albuterol (salbutamol). There were no differences in nocturnal symptoms between periods of treatment, and no side effects were recorded. We conclude that anticholinergic drugs may protect against nocturnal asthma in some patients, indicating the involvement of vagal cholinergic mechanisms.",
"The role of the anticholinergic drug, ipratropium bromide, in maintenance antiasthmatic therapy was evaluated in a double-blind crossover trial of three bronchodilator regimens: (1) inhaled ipratropium, placebo, and oral oxtriphylline; (2) inhaled fenoterol, placebo, and oral oxtriphylline; and (3) both inhaled ipratropium and fenoterol plus oral oxtriphylline. Twenty-two asthmatics were treated with all three regimens, each for 1 mo, allocated in random sequence. On the first and last treatment days of each month, spirometric measurements were performed before and 0.5, 1, 2, 3, 4, and 6 hr after administration of the test drugs. On the first treatment day of each month, all regimens produced significant bronchodilatation at 30 min after dose, an improvement that declined between 3 and 6 hr after dose. After continuous administration for 1 mo the two combinations employing fenoterol showed a decline in bronchodilator responsiveness from the initial treatment day, measured as the level of response (V50) or duration of response (FEV1, VC). Ipratropium plus oxtriphylline showed no such decline, suggesting the development of tolerance to long-term administration of fenoterol. Overall benefit at the end of 1 mo, measured as the area under the curves of FEV1, VC, or V50 vs time after dose, was greatest for the triple drug regimen. There were no differences in heart rate, blood pressure response, or side effects among the three treatments. It is concluded that when the anticholinergic drug ipratropium is administered concurrently with an inhaled beta 2 agonist and an oral theophylline derivative, increased bronchodilatation occurs with no detectable additional side effects.",
"Outcome data are needed to base recommendations for controller asthma medication use in school-aged children.\n We sought to determine intraindividual and interindividual response profiles and predictors of response to an inhaled corticosteroid (ICS) and a leukotriene receptor antagonist (LTRA).\n An ICS, fluticasone propionate (100 mug twice daily), and an LTRA, montelukast (5-10 mg nightly, age dependent), were administered to children ages 6 to 17 years with mild-to-moderate persistent asthma using only as-needed bronchodilators in a multicenter, double-masked, 2-sequence, 16-week crossover trial. Clinical, pulmonary, and inflammatory responses to these controllers were evaluated.\n Improvements in most clinical asthma control measures occurred with both controllers. However, clinical outcomes (asthma control days [ACDs], the validated Asthma Control Questionnaire, and albuterol use), pulmonary responses (FEV(1)/forced vital capacity, peak expiratory flow variability, morning peak expiratory flow, and measures of impedance), and inflammatory biomarkers (exhaled nitric oxide [eNO]) improved significantly more with fluticasone than with montelukast treatment. eNO was both a predictor of ACDs (P = .011) and a response indicator (P = .003) in discriminating the difference in ACD response between fluticasone and montelukast.\n The more favorable clinical, pulmonary, and inflammatory responses to an ICS than to an LTRA provide pediatric-based group evidence to support ICSs as the preferred first-line therapy for mild-to-moderate persistent asthma in children. eNO, as a predictor of response, might help to identify individual children not receiving controller medication who achieve a greater improvement in ACDs with an ICS compared with an LTRA.",
"Currently available anti-inflammatory treatment for young children with asthma includes inhaled corticosteroids (ICS) and the leukotriene receptor antagonist (LTRA) montelukast.\n To evaluate potential biomarkers of predicting short-term (6-week) response to ICS and LTRAs in children with asthma.\n A total of 102 children aged 4 to 7 years with episodic asthma were enrolled in an open labelled single-centre study. Biomarkers and asthma characteristics were evaluated as predictors of treatment. Of 102 patients 45 became symptomatic during observation and were randomised to treatment either to montelukast or fluticasone for 6 weeks.\n Forced Expiratory Volume in one second (FEV1) increased with both treatments: FEV1 at randomisation was 90.2% and after therapy 106.8% with fluticasone vs. 90.8% and 103.7% for montelukast, respectively, showing that montelukast and fluticasone were equally effective in this age group (p = 0.44). Strong correlations to a favourable treatment response were pre-bronchodilatory FEV1 (p < 0.001) and airway reversibility (p = 0.04) at time of randomisation. None of the other biomarkers (methacholine testing, exhaled nitric oxide [eNO], presence of allergy, total Immunoglobulin E [IgE], cumulative specific IgE, eosinophils and parental smoking) were predictive.\n Despite the small sample size and the open-label design, the study suggests that the use of pre-bronchodilatory FEV1 and airway reversibility appears to be a good indicator of short-term anti-inflammatory therapy in young children with asthma.",
"Eighteen children with severe, chronic bronchial asthma were randomly divided into two groups. The families in one group received family therapy while the others served as a control group in a controlled family therapy study. Later the control families were also offered therapy in a before-after therapy design. All children were followed for 3 1/2 yr. Asthma symptoms, functional impairment and the use of drug (from diaries) were rated in ten different ways during eight months before and eight months after the family therapy. Improvement in the clinically most important variable, i.e. general pediatric assessment, was greater in the children in the family therapy group compared to the control group (p less than 0.05) Twelve children who received family therapy showed significant improvement after treatment concerning general pediatric assessment (p less than 0.01), clinical grading (p less than 0.05), peak expiratory flow (p less than 0.05), days with functional impairment/yr (p less than 0.05), no. of doses of inhaled Beta-2-agonists/month (p less than 0.01) and nights when Beta-2-agonists were inhaled (p less than 0.05). The children who only received conventional medical treatment showed no significant change in asthma symptoms. We draw the conclusion that family therapy may represent a valuable therapeutic tool in the management of severe asthma.",
"The effect of slow-release aminophylline, salbutamol and a half dose combination of both was compared in children with chronic asthma. Drugs were given over three consecutive 5-week periods during which patients recorded daily peak flow measurements and symptom scores. At the end of each treatment period pulmonary function tests were done. Sixteen of twenty-nine children completed the trial satisfactorily and their results have been used for analysis. The data show slow-release aminophylline and salbutamol to be equally effective and the half dose combination as effective as either drug alone. The results suggest there may be a therapeutic advantage in combining a beta 2 agonist with theophylline when high doses of either drug alone are not fully effective or when toxic effects occur.",
"To evaluate the effects of aminophylline (Am) in children hospitalized with asthma.\n Prospective, randomized, double-blind, placebo-controlled trial. Subjects were children between the ages of 5 and 18 years admitted for asthma exacerbation to either a tertiary care children's hospital or an inner-city general hospital in New York. Exclusion criteria were admission to the intensive care unit, initial theophylline level > 5 micrograms/dL, or the presence of other systemic disorders. All patients received nebulized albuterol therapy and intravenous glucocorticosteroids in standardized doses. Thirty-one patients were randomized to receive either an Am bolus followed by continuous Am infusion or placebo (P) bolus and infusion. The outcome variables were: duration of hospitalization, percent of predicted peak expiratory flow rates recorded at 12-hour intervals, number of albuterol treatments required, and adverse effects.\n There were no significant differences at study entry in age, sex, race, number of previous hospital admissions, prior medications used, clinical symptom scores, or initial peak flow rates for the two groups. For 26 patients who completed this study, 15 patients in the P group were hospitalized for a mean duration of 2.33 +/- 1.3 days, whereas 11 patients in the Am group required 2.58 +/- 1.5 days. There were no significant differences between the two groups for hospital days, peak flow rates at any time interval, or amount of albuterol therapy required (P > .2). In the Am group, 6 of the 14 patients who entered the study experienced significant adverse effects consisting of nausea, emesis, headache, abdominal pain, and palpitations. Only 1 of 17 patients in the P group had an adverse effect (P < .05).\n There is no benefit and considerable risk of adverse effects associated with the use of Am in hospitalized asthmatic children.",
"The effectiveness of nebulized anticholinergic and sympathomimetic regimens was evaluated in a double-blind study of 199 patients with acute airways obstruction. Patients were assigned to one of three treatment regimens according to a randomized schedule: 0.5 mg of ipratropium bromide, 1.25 mg of fenoterol hydrobromide, and 0.5 mg of ipratropium plus 1.25 mg of fenoterol. In 148 patients with acute exacerbations of asthma (mean one-second forced expiratory volume, 1.18 +/- 0.64 liters), all three regimens produced significant improvement in one-second forced expiratory volume (p less than 0.001). The greatest improvement followed treatment with the ipratropium-fenoterol combination (0.53 +/- 0.40 liters at 45 minutes; 0.57 +/- 0.51 liters at 90 minutes) and was significantly greater than that following either ipratropium alone (p less than 0.001) or fenoterol alone (p less than 0.05). In 51 patients with acute exacerbations of chronic obstructive pulmonary disease (mean one-second forced expiratory volume, 0.67 +/- 0.29 liter), each regimen produced significant improvement in one-second forced expiratory volume at both 45 and 90 minutes (for all, p less than 0.05), but there was no significant difference among the three treatment regimens. It is concluded that, in patients with acute asthma, combination therapy with sympathomimetic and anticholinergic agents is more efficacious than either one alone. In patients with acute exacerbations of chronic obstructive pulmonary disease, although either sympathomimetic or anticholinergic therapy provides bronchodilatation, no further benefit could be demonstrated from combination therapy."
] |
The present review summarises the best evidence available to date. Although there were some small beneficial findings in favour of anticholinergic therapy, there is insufficient data to support the use of anticholinergic drugs in the maintenance treatment of chronic asthma in children.
|
CD004325
|
[
"19181969",
"10424554",
"12130413"
] |
[
"Treatment with and without initial stabilizing surgery for primary traumatic patellar dislocation. A prospective randomized study.",
"Prospective randomized clinical trial comparing the effectiveness of immediate arthroscopic stabilization versus immobilization and rehabilitation in first traumatic anterior dislocations of the shoulder.",
"A prospective, randomized evaluation of arthroscopic stabilization versus nonoperative treatment in patients with acute, traumatic, first-time shoulder dislocations."
] |
[
"There is no consensus about the management of acute primary traumatic patellar dislocation in young physically active adults. The objective of this study was to compare the clinical outcomes after treatment with and without initial stabilizing surgery for primary traumatic patellar dislocation in young adults.\n Forty young adults, thirty-seven men and three women with a median age of twenty years (range, nineteen to twenty-two years), who had an acute primary traumatic patellar dislocation were randomly allocated to be treated with initial surgical stabilization (eighteen patients, with each receiving one of two types of initial stabilizing procedures) or to be managed with an orthosis (twenty-two patients, including four who had osteochondral fragments removed arthroscopically). After a median of seven years, thirty-eight patients returned for a follow-up examination. Redislocations, subjective symptoms, and functional limitations were evaluated. Radiographs and magnetic resonance images were obtained at the time of randomization, and twenty-nine (76%) patients underwent magnetic resonance imaging at the time of final follow-up.\n A hemarthrosis as well as injuries of the medial retinaculum and the medial patellofemoral ligament were found on magnetic resonance imaging in all patients at the time of randomization. During the follow-up period, six of the twenty-one nonoperatively treated patients and none of the seventeen patients treated with surgical stabilization had a redislocation (p = 0.02). Four nonoperatively treated patients and two patients treated with surgical stabilization reported painful patellar subluxation. The median Kujala scores were 91 points for the surgically treated patients and 90 points for the nonoperatively treated patients. Thirteen patients in the surgically treated group and fifteen in the nonoperatively treated group regained their former physical activity level. At the time of follow-up, a full-thickness patellofemoral articular cartilage lesion was detected on magnetic resonance imaging in eleven patients; the lesions were considered to be unrelated to the form of treatment.\n In a study of young, mostly male adults with primary traumatic patellar dislocation, the rate of redislocation for those treated with surgical stabilization was significantly lower than the rate for those treated without surgical stabilization. However, no clear subjective benefits of initial stabilizing surgery were seen at the time of long-term follow-up.",
"Our purpose was to compare the effectiveness of traditional treatment with immediate arthroscopic stabilization in young patients who have sustained a first traumatic anterior dislocation of the shoulder. Forty skeletally mature patients younger than 30 years of age were randomly allocated to immobilization for 3 weeks followed by rehabilitation (group T) or arthroscopic stabilization (within 4 weeks of injury) followed by an identical immobilization and rehabilitation protocol (group S). A blinded research assistant performed all follow-up evaluations. The dominant arm was involved in 35% of subjects. The injury occurred in a sporting event in 70% of subjects. At 24 months, there was a statistically significant difference in the rate of redislocation (T = 47%, S = 15.9%, P = .03). An intention-to-treat analysis comparing disease-specific quality of life using the validated Western Ontario Shoulder Instability (WOSI) index showed statistically significantly better results in the surgically treated group at the 33 months (T = 633.93 v S = 287.1, P = .03) and no significant difference in range of motion. At an average 32 months follow-up, a significant reduction in redislocation and improvement in disease-specific quality of life is afforded by early arthroscopic stabilization in patients less than 30 year of age with a first, traumatic, anterior dislocation of the shoulder.",
"Nonoperative treatment of traumatic shoulder dislocations leads to a high rate of recurrent dislocations.\n Early arthroscopic treatment for shoulder dislocation will result in a lower recurrence rate than nonoperative treatment.\n Prospective, randomized clinical trial.\n Two groups of patients were studied to compare nonoperative treatment with arthroscopic Bankart repair for acute, traumatic shoulder dislocations in young athletes. Fourteen nonoperatively treated patients underwent 4 weeks of immobilization followed by a supervised rehabilitation program. Ten operatively treated patients underwent arthroscopic Bankart repair with a bioabsorbable tack followed by the same rehabilitation protocol as the nonoperatively treated patients. The average follow-up was 36 months.\n Three patients were lost to follow-up. Twelve nonoperatively treated patients remained for follow-up. Nine of these (75%) developed recurrent instability. Six of the nine have required subsequent open Bankart repair for recurrent instability. Of the nine operatively treated patients available for follow-up, only one (11.1%) developed recurrent instability.\n Arthroscopic stabilization of traumatic, first-time anterior shoulder dislocations is an effective and safe treatment that significantly reduces the recurrence rate of shoulder dislocations in young athletes when compared with conventional, nonoperative treatment."
] |
Limited evidence supports primary surgery for young adults, usually male, engaged in highly demanding physical activities who have sustained their first acute traumatic shoulder dislocation. There is no evidence available to determine which treatment is better for other patient groups.
Sufficiently powered, good quality, well reported randomised trials are required that compare surgical treatment with conservative treatment for these injuries, including in people at lower risk of recurrence. Long-term surveillance of outcome, looking at shoulder disorders including osteoarthritis is also required.
|
CD002865
|
[
"8018638",
"9794673",
"1448266",
"9764616",
"10535343",
"15672012"
] |
[
"Mifepristone for labour induction after previous caesarean section.",
"The effects of mifepristone on cervical ripening and labor induction in primigravidae.",
"Labor induction in women at term with mifepristone (RU 486): a double-blind, randomized, placebo-controlled study.",
"Cervical ripening with mifepristone before labor induction: a randomized study.",
"Induction of labor with mifepristone--a randomized, double-blind study versus placebo.",
"Use of mifepristone to ripen the cervix and induce labor in term pregnancies."
] |
[
"To evaluate the efficacy and tolerance of mifepristone in women undergoing induction of labour at term after previous caesarean section.\n A prospective double blind placebo controlled trial.\n Thirty-two women at term (after 37.5 weeks' amenorrhea) who had had a previous caesarean delivery with a low transverse uterine incision. All women had a clear clinical indication for induction of labour with unfavourable cervical conditions (Bishop's score < 4). They were randomised to receive either 200 mg of mifepristone or placebo on days one and two of a four-day observation period.\n Thirteen women entered spontaneous labour: 11 were treated with mifepristone and two were in the control group (P < 0.01). Thirteen women, still with an unfavourable cervix on day four needed cervical ripening with vaginal tablets of prostaglandins. Of these, four had received mifepristone and nine the placebo. Mean oxytocin requirements were lower in the mifepristone group (P < 0.01) and the mean time interval between day one and start of labour was also significantly shorter in this group. Mode of delivery and neonatal outcome were similar in both groups.\n Induction of labour is facilitated in term women with prior caesarean section by the use of mifepristone. This induction agent appears safe and useful with no adverse events on the fetus or mother.",
"To compare the effects of 50 mg or 200 mg of oral mifepristone with placebo on cervical ripening and induction of labor in primigravid women at term with unfavorable cervices.\n This was a double-blind study in which 80 primigravidae at term with a modified Bishop score of 4 or less were randomly assigned to one of three treatment groups. They were assessed at 24-hour intervals for 72 hours, after which labor was induced if it had not occurred spontaneously.\n Two hundred milligrams of mifepristone resulted in a favorable cervix (with a Bishop score greater than 6 or in spontaneous labor) in significantly more women than placebo (P = .01). An improvement in cervical ripening was seen in the group given 50 mg of mifepristone, but this was not statistically significant. There were more cesarean deliveries performed for fetal distress in the group treated with 200 mg of mifepristone than placebo, but this was not statistically significant and was not associated with any differences between groups in terms of neonatal outcome.\n Mifepristone, a progesterone antagonist, is known to cause softening and dilation of the human early pregnant cervix and an increase in uterine activity. It is theoretically attractive for use as an adjunct in cervical priming and labor induction. In this study, 200 mg of mifepristone was significantly more likely to result in a favorable cervix than placebo.",
"To determine the efficacy and safety of mifepristone as an induction agent for the initiation of labor or as a cervical ripening agent in women at term.\n Our study group contained 120 women at term (after 37.5 weeks' amenorrhea) who had clear clinical indications for labor induction. They were randomized to receive either 200 mg of mifepristone or placebo on days 1 and 2 of a 4-day observation period, with labor induction planned for day 4. Eight patients, three treated with mifepristone and five receiving placebo, had to be excluded from the survey because they required cesareans for medical reasons (fetal distress or maternal complications) less than 12 hours after taking the first tablet.\n Forty-one subjects entered spontaneous labor, 31 treated with mifepristone and ten in the control group (P < .001). Forty-five needed cervical maturation with prostaglandins on day 4, 13 of whom had received mifepristone and 32 of whom had been given placebo (P < .001). Thirteen women treated with mifepristone and 13 who had taken placebo had mature cervices sufficient for classic labor induction with oxytocin and amniotomy. Patients who delivered vaginally needed a much lower amount of oxytocin when mifepristone had been given, and the mean time interval between day 1 of the survey and the onset of labor was also significantly shorter in this group.\n Although more studies are needed, we have found mifepristone to be a safe, efficient, and suitable induction agent for initiation of labor in women at term.",
"To determine the efficacy and safety of mifepristone for cervical ripening in post-term pregnancies.\n Women with post-term pregnancies and Bishop scores less than 6 were assigned randomly to mifepristone (41 patients) or placebo (42 patients). Mifepristone was given orally in a dose of 400 mg. Efficacy was assessed by change in the Bishop score within 48 hours after treatment; a score of 6 or greater was considered a \"strict\" success. An \"extended\" success rate was defined, including all patients with scores of at least 6 or those who delivered within 48 hours of treatment. Antenatal safety was assessed by fetal heart rate testing before and throughout labor. Neonatal safety was assessed by Apgar score, arterial or venous pH of cord blood, and blood glucose level during the first 48 hours. Analysis used Student t test for continuous variables, Kruskal-Wallis test for ordinal data, and chi2 for categoric variables.\n Strict success was achieved in 10 of 18 mifepristone patients (55%) evaluated for Bishop score on day 2 versus 8 of 29 placebo patients (27.5%) (P=.004). Extended success was achieved in 33 mifepristone patients (80.5%) and 21 placebo patients (50.0%) (P=.004). There were no statistical differences with regard to number of cesareans or fetal and neonatal safety.\n Mifepristone proved effective for cervical ripening and reduced the time to delivery compared with placebo, but it did not improve the rate of cesarean. Our study did not include enough pregnancies to reach conclusions about fetal or neonatal safety.",
"To evaluate the efficacy of mifepristone in inducing labor in women with an unripe cervix, its effect on the cervix and on the status of the newborn.\n In a prospective double-blind study, 36 post-term pregnant women with a Bishop score of 5 or less received either 400 mg mifepristone (n=24) or placebo (n=12). If, 48 hours after the treatment was started, labor had not begun or the Bishop score was 5 or less, the women were given 0.5 mg prostaglandin E2 intracervically, a treatment which was repeated 12 hours later, if necessary.\n During the first 48 hours following treatment, 19 (79.2%) of the women treated with mifepristone and two of the women (16.7%) treated with placebo went into labor. In addition, one and three women, respectively, had a ripe cervix at the end of the 48h period. The overall success rate was thus 83.3% for mifepristone and 41.7% for placebo (p=0.008; OR 14.8; 95% CI 2.1-107.6). The median time from the start of treatment to delivery was also shorter (mifepristone 36h23' and placebo 53h17'). Treatment with intracervical PGE2 was needed more often after the placebo. The duration of labor, however, tended to be shorter after placebo than after mifepristone in the women who delivered vaginally. The frequencies of instrumental delivery were similar in both treatment groups. The median Apgar score was slightly lower at 1 minute (p<0.05) following mifepristone treatment, but did not differ at 5 and 10 minutes. There was no difference between the two treatment groups in the umbilical pH at delivery.\n The results of the present study show that mifepristone is a simple and effective treatment for inducing labor in post-term women with an unripe cervix.",
"This study was undertaken to determine the efficacy of mifepristone for ripening the cervix and inducing labor in term pregnancies.\n In a double-blind placebo-controlled dose-finding study, 346 women received 50, 100, 200, 400, or 600 mg of mifepristone or placebo. The main endpoint for efficacy was the number of patients in whom labor occurred between 12 and 45 and 54 hours after treatment or who had a Bishop score 6 or greater. Maternal and fetal tolerability was also studied.\n No significant efficacy was observed whatever the dose of mifepristone. Mifepristone was well tolerated by the mother and fetus.\n Mifepristone, at doses up to 600 mg, does not induce labor within 54 hours in patients with unfavourable cervical status."
] |
There is insufficient information available from clinical trials to support the use of mifepristone to induce labour. However, the studies suggest that mifepristone is better than placebo in reducing the likelihood of caesarean sections being performed for failed induction of labour; therefore, this may justify future trials comparing mifepristone with the routine cervical ripening agents currently in use. There is little information on effects on the baby.
|
CD001180
|
[
"8671131",
"15580451",
"1390143",
"9228227",
"16984453",
"9682649",
"3528240"
] |
[
"A randomized controlled trial of electromagnetic therapy in the primary care management of venous leg ulceration.",
"[Venous leg ulcers: no improvement of wound healing with 685-nm low level laser therapy. Randomised, placebo-controlled, double-blind study].",
"A portable pulsed electromagnetic field (PEMF) device to enhance healing of recalcitrant venous ulcers: a double-blind, placebo-controlled clinical trial.",
"Low-frequency ultrasound treatment of chronic venous leg ulcers in an outpatient therapy.",
"Low-frequency ultrasound treatment of chronic venous ulcers.",
"A prospective randomised trial of four-layer versus short stretch compression bandages for the treatment of venous leg ulcers.",
"Systemic administration of antibiotics in the management of venous ulcers. A randomized clinical trial."
] |
[
"The aim was to establish the potential efficacy, tolerability and side-effect profile of electromagnetic therapy as an adjunct to conventional dressings in the treatment of venous leg ulcers.\n A prospective, randomized, double blind controlled clinical trial was carried out in a dedicated leg ulcer clinic based in one urban general practice. Nineteen patients with leg ulcers of confirmed venous aetiology were assessed. The main outcome measures were rate and scale of venous leg ulcer healing, changes in patient-reported pain levels, quality of life, degree of mobility, side effect profile and acceptability to patients and staff.\n Sixty-eight per cent of patients attending this dedicated clinic achieved improvements in the size of their ulcer (4, 21%, healed fully) and in reduced pain levels (P < 0.05) during the trial, despite the chronicity of ulcer histories. Patients treated with electromagnetic therapy at 800 Hz were found at day 50 to have significantly greater healing (P < 0.05) and pain control (P < 0.05) than placebo therapy or treatment with 600 Hz. All patients reported improved mobility at the end of the study. The electromagnetic therapy was well tolerated by patients, with no differences between groups in reporting adverse events, and proved acceptable to staff.\n Despite the small numbers in this pilot study, electromagnetic therapy provided significant gains in the healing of venous leg ulcers and reduction in pain.",
"Venous leg ulcers (ulcera crurum venosa) are frequently seen in elderly patients. It has been suggested that low level laser irradiation has a biostimulative and wound healing effect; however, this has not yet been clinically verified by controlled studies.\n The difference in size reduction of leg ulcers with and without low level laser or placebo laser treatment was measured in 44 patients randomised into two treatment groups (685-nm low level laser and placebo laser) or a control group which served to quantify the effect of laser application. All patients received standardized wound care.\n The aim of the study was to compare the effectiveness of low level laser irradiation with that of a placebo \"light source\". The size of the ulcers was planimetrically measured at baseline (day 1), at the end of therapy (day 28) and 2 months later (day 90). The difference in wound size was evaluated.\n There were no statistically significant differences in reduction of wound size between the three groups, thus suggesting that low level laser light does not have any stimulatory effect on wound healing in ulcera crurum venosa.",
"A prospective, randomized, double-blind, placebo-controlled multicentre study assessed the clinical efficacy and safety of pulsed electromagnetic limb ulcer therapy (PELUT) in the healing of recalcitrant, predominantly venous leg ulcers. The portable device was used at home for 3 h daily during this 8-week clinical trial as an adjunct to a wound dressing. Wound surface area, ulcer depth and pain intensity were assessed at weeks 0, 4 and 8. At week 8 the active group had a 47.7% decrease in wound surface area vs. a 42.3% increase for placebo (P < 0.0002). Investigators' global evaluations indicated that 50% of the ulcers in the active group healed or markedly improved vs. 0% in the placebo group, and 0% of the active group worsened vs. 54% of the placebo group (P < 0.001). Significant decreases in wound depth (P < 0.04) and pain intensity (P < 0.04) favouring the active group were seen. Patients whose ulcers improved significantly after 8 weeks were permitted to continue double-blind therapy for an additional 4 weeks. Eleven active and one placebo patient continued therapy until week 12, with the active treatment group continuing to show improvement. There were no reports of adverse events attributable to this device. We conclude that the PELUT device is a safe and effective adjunct to non-surgical therapy for recalcitrant venous leg ulcers.",
"Low-dose ultrasound seems to be an effective method to enhance wound healing, particularly in chronic venous leg ulcers. The aim of our investigation was to examine the effect of 30 kHz low-dose ultrasound in local treatment of chronic venous leg ulcers, when added to conventional therapy of outpatients. Twenty-four patients with chronic ulcerations of the leg due to chronic venous insufficiency were randomised in placebo-controlled parallel groups in a single-blind clinical study. Patients were randomised to conventional therapy with topical application of hydrocolloid dressings and compression therapy or conventional therapy with additional ultrasound treatment for 12 weeks. The ultrasound treatment consisted of 10 min of footbathing, with application of 30 kHz continuous ultrasound 100 mW/cm2 three times a week. The ulcer area was measured by planimetry, using a millimeter grid before treatment and after 2, 4, 6, 8, 10 and 12 weeks of therapy. The ulcer radius and the daily ulcer radius reduction were calculated. Colour photographs of the ulcers were taken under standard conditions at the same time. After each treatment local findings and side effects were recorded. After 12 weeks of treatment the control group showed a mean decrease of 16.5% in the ulcerated area. In contrast the mean ulcerated area decreased by 55.4% in the ultrasound group (p<0.007). The daily ulcer reduction in the ultrasound-treated patients was 0.08 mm+/-0.04 mm and in the placebo patients 0.03 mm+/-0.03 mm. Patients recorded only minor side-effects such as a tingling feeling and occasionally pinhead-sized bleeding in the ulcer area. The application of low-frequency and low-dose ultrasound is a helpful treatment option in chronic venous leg ulcers, especially if they do not respond to conventional ulcer treatment.",
"In a randomized controlled clinical trial, the properties of low-frequency ultrasound in the treatment of chronic venous ulcers were investigated. Thirty-eight patients with chronic ulcerations of the legs caused by chronic venous insufficiency were randomly assigned to receive either conventional therapy alone or conventional therapy plus additional 30 kHz ultrasound treatment. Patients with other conditions that may impair wound healing such as diabetes mellitus or arterial disease were excluded. The ultrasound treatment consisted of 10 minutes of foot bathing with application of 30 kHz ultrasound 100 mW/cm(2) three times a week. Response was evaluated with the use of planimetry of the ulcer area and compared with controls after 3 and 8 weeks. After 3 weeks of treatment (and to a greater extent after 8 weeks of treatment) the ultrasound group showed a markedly better response than the control group. Although the control group showed a mean decrease of 11% in the ulcerated area after 8 weeks, in the ultrasound group the mean ulcerated area decreased by 41% (p < 0.05). There were only mild side effects in some of the patients treated with ultrasound. In conclusion, application of low-frequency ultrasound may be a helpful treatment option in chronic venous leg ulcers.",
"This trial was undertaken to examine the safety and efficacy of four-layer compared with short stretch compression bandages for the treatment of venous leg ulcers within the confines of a prospective, randomised, ethically approved trial. Fifty-three patients were recruited from a dedicated venous ulcer assessment clinic and their individual ulcerated limbs were randomised to receive either a four-layer bandage (FLB)(n = 32) or a short stretch bandage (SSB)(n = 32). The endpoint was a completely healed ulcer. However, if after 12 weeks of compression therapy no healing had been achieved, that limb was withdrawn from the study and deemed to have failed to heal with the prescribed bandage. Leg volume was measured using the multiple disc model at the first bandaging visit, 4 weeks later, and on ulcer healing. Complications arising during the study were recorded. Data from all limbs were analysed on an intention to treat basis; thus the three limbs not completing the protocol were included in the analysis. Of the 53 patients, 50 completed the protocol. At 1 year the healing rate was FLB 55% and SSB 57% (chi 2 = 0.0, df = 1, P = 1.0). Limbs in the FLB arm of the study sustained one minor complication, whereas SSB limbs sustained four significant complications. Leg volumes reduced significantly after 4 weeks of compression, but subsequent volume changes were insignificant. Ulcer healing rates were not influenced by the presence of deep venous reflux, post-thrombotic deep vein changes nor by ulcer duration. Although larger ulcers took longer to heal, the overall healing rates for large (> 10 cm2) and small (10 cm2 or less) ulcers were comparable. Four-layer and short stretch bandages were equally efficacious in healing venous ulcers independent of pattern of venous reflux, ulcer area or duration. FLB limbs sustained fewer complications than SSB.",
"Forty-seven patients with chronic venous leg ulcers were included in a randomized clinical trial to evaluate the efficacy of systemically administered antibiotics in healing with condition. One group was treated by means of elastic support bandages only, whereas the other one received the same local treatment plus systemic antibiotics. No statistically relevant difference was noted between the two groups in healing rates of ulcers or in changes of the microbiologic flora. The results of our study do not support the routine administration of systemic antibiotics in the management of chronic venous leg ulcers."
] |
The trials evaluating US for venous leg ulcers are small, poor-quality and heterogeneous. There is no reliable evidence that US hastens healing of venous ulcers. There is a small amount of weak evidence of increased healing with US, but this requires confirmation in larger, high-quality RCTs. There is no evidence of a benefit associated with low frequency US.
|
CD003004
|
[
"20156348",
"12357146"
] |
[
"Goal-directed intraoperative therapy based on autocalibrated arterial pressure waveform analysis reduces hospital stay in high-risk surgical patients: a randomized, controlled trial.",
"Goal-directed intraoperative fluid administration reduces length of hospital stay after major surgery."
] |
[
"Several studies have shown that goal-directed hemodynamic and fluid optimization may result in improved outcome. However, the methods used were either invasive or had other limitations. The aim of this study was to perform intraoperative goal-directed therapy with a minimally invasive, easy to use device (FloTrac/Vigileo), and to evaluate possible improvements in patient outcome determined by the duration of hospital stay and the incidence of complications compared to a standard management protocol.\n In this randomized, controlled trial 60 high-risk patients scheduled for major abdominal surgery were included. Patients were allocated into either an enhanced hemodynamic monitoring group using a cardiac index based intraoperative optimization protocol (FloTrac/Vigileo device, GDT-group, n = 30) or a standard management group (Control-group, n = 30), based on standard monitoring data.\n The median duration of hospital stay was significantly reduced in the GDT-group with 15 (12 - 17.75) days versus 19 (14 - 23.5) days (P = 0.006) and fewer patients developed complications than in the Control-group [6 patients (20%) versus 15 patients (50%), P = 0.03]. The total number of complications was reduced in the GDT-group (17 versus 49 complications, P = 0.001).\n In high-risk patients undergoing major abdominal surgery, implementation of an intraoperative goal-directed hemodynamic optimization protocol using the FloTrac/Vigileo device was associated with a reduced length of hospital stay and a lower incidence of complications compared to a standard management protocol.\n Clinical trial registration information: Unique identifier: NCT00549419.",
"Intraoperative hypovolemia is common and is a potential cause of organ dysfunction, increased postoperative morbidity, length of hospital stay, and death. The objective of this prospective, randomized study was to assess the effect of goal-directed intraoperative fluid administration on length of postoperative hospital stay.\n One hundred patients who were to undergo major elective surgery with an anticipated blood loss greater than 500 ml were randomly assigned to a control group (n = 50) that received standard intraoperative care or to a protocol group (n = 50) that, in addition, received intraoperative plasma volume expansion guided by the esophageal Doppler monitor to maintain maximal stroke volume. Length of postoperative hospital stay and postoperative surgical morbidity were assessed.\n Groups were similar with respect to demographics, surgical procedures, and baseline hemodynamic variables. The protocol group had a significantly higher stroke volume and cardiac output at the end of surgery compared with the control group. Patients in the protocol group had a shorter duration of hospital stay compared with the control group: 5 +/- 3 versus 7 +/- 3 days (mean +/- SD), with a median of 6 versus 7 days, respectively ( = 0.03). These patients also tolerated oral intake of solid food earlier than the control group: 3 +/- 0.5 versus 4.7 +/- 0.5 days (mean +/- SD), with a median of 3 versus 5 days, respectively ( = 0.01).\n Goal-directed intraoperative fluid administration results in earlier return to bowel function, lower incidence of postoperative nausea and vomiting, and decrease in length of postoperative hospital stay."
] |
Invasive methods of fluid optimization during surgery may shorten hospital stay, but their effects on other important, patient-centred, longer-term outcomes are uncertain. Adverse effects on fatality cannot be excluded. Other fluid optimization techniques have not been evaluated. The lack of randomized studies of adequate quality addressing this important question is disappointing. More research is needed.
|
CD003628
|
[
"8938179",
"9197351",
"12297843",
"10098582",
"10798755",
"17532088",
"2119446",
"1727754",
"7843707",
"16278591",
"3142949",
"7969324",
"17697262",
"3307390"
] |
[
"Pilot-controlled trial of the extracorporeal liver assist device in acute liver failure.",
"The Nordic multicenter double-blind randomized controlled trial of prophylactic ursodeoxycholic acid in liver transplant patients.",
"Albumin dialysis in cirrhosis with superimposed acute liver injury: a prospective, controlled study.",
"Temporary extracorporeal liver support for severe acute alcoholic hepatitis using the BioLogic-DT.",
"A prospective randomized study of preoperative nutritional supplementation in patients awaiting elective orthotopic liver transplantation.",
"A randomized trial of antioxidant therapy alone or with corticosteroids in acute alcoholic hepatitis.",
"Nutritional support after liver transplantation: a randomized prospective study.",
"Accelerated improvement of alcoholic liver disease with enteral nutrition.",
"A double-blind, randomized, placebo-controlled trial of prostaglandin E1 in liver transplantation.",
"Prevention of renal impairment by continuous infusion of human atrial natriuretic peptide after liver transplantation.",
"A randomized controlled study of peripheral parenteral nutrition in moderate and severe alcoholic hepatitis.",
"Perioperative nutritional support in patients undergoing hepatectomy for hepatocellular carcinoma.",
"Ischemic pre-conditioning in deceased donor liver transplantation: a prospective randomized clinical trial.",
"A prospective randomized clinical trial of peripheral amino acid-glucose supplementation in acute alcoholic hepatitis."
] |
[
"The objective of this pilot controlled study was to evaluate the extracorporeal liver assist device (ELAD) in patients with acute liver failure who were judged to still have a significant chance of survival (approximately 50%) and in those who had already fulfilled criteria for transplantation. Twenty-four patients were divided into two groups, 17 with a potentially recoverable lesion (group I) and 7 listed for transplantation (group II), and then randomly allocated to ELAD haemoperfusion or control. The median period of ELAD haemoperfusion was 72 hours (range 3-168 h). Biocompatibility of the device was good, with no acceleration in platelet consumption, and haemodynamic stability was maintained. Two patients were withdrawn from the study because of worsening of preexisting disseminated intravascular coagulation in one case and a hypersensitivity reaction in the other. Deterioration with respect to encephalopathy grade was more frequent in the control patients, 7 of 12 (58%), than in the ELAD-treated patients, 3 of 12 (25%). In group I where survival for the ELAD cases was 7 of 9 (78%), there was a higher than expected survival in the controls, 6 of 8 (75%). For group II cases, survival was 1 of 3 (33%) for the ELAD-treated patients, and 1 of 4 (25%) for the controls. Both of the survivors underwent transplantation. Assessment of additive function for the device revealed an improvement in galactose elimination capacity after 6 hours of haemoperfusion. Based on the results of this pilot-controlled trial, better indices of prognosis will be required, in addition to those used to select for transplantation, if patients at an earlier stage of clinical deterioration are to be included in future studies.",
"Prophylactic treatment with ursodeoxycholic acid (UDCA) has been reported to reduce the incidence of acute rejection after liver transplantation compared with historical controls. We investigated this in a prospective, randomized, placebo-controlled multicenter study.\n Fifty-four liver transplant patients were allocated to the UDCA treatment group (15 mg/kg/day), and 48 patients were allocated to the placebo group. Trial medicine was started on the first postoperative day and was given for 3 months. Follow-up was for 12 months. Treatment was stratified for adults with chronic liver disease (n=77), adults with acute liver failure (n=10), and children (n=15).\n The frequency of patients with acute rejection was 65% in the UDCA treatment group and 68% in the placebo group. The frequency of steroid-resistant rejection was similar in both groups. The probability of acute rejection, analyzed according to the intention-to-treat policy with Kaplan-Meier analysis, was similar in both treatment groups. No significant differences were found in patient survival and graft survival probabilities. For the biochemical markers of cholestasis, only gamma-glutamyltransferase was significantly improved after 2 months of UDCA treatment.\n The initial optimistic report of a beneficial effect of prophylactic treatment with UDCA on acute rejection after liver transplantation was not confirmed in this controlled study.",
"Patients with liver cirrhosis and a superimposed acute injury with progressive hyperbilirubinemia have a high mortality. A prospective, controlled study was performed to test whether hyperbilirubinemia, 30-day survival, and encephalopathy would be improved by extracorporeal albumin dialysis (ECAD). Twenty-four patients were studied; 23 patients had cirrhosis; 1 had a prolonged cholestatic drug reaction and was excluded from per protocol (PP) analysis. Patients had a plasma bilirubin greater than 20 mg/dL and had not responded to prior standard medical therapy (SMT). Patients were randomized to receive SMT with ECAD or without (control). ECAD was performed with an extracorporeal device that dialyzes blood in a hollow fiber dialyzer (MW cutoff < 60 kd) against 15% albumin. Albumin-bound molecules transfer to dialysate albumin that is regenerated continuously by passage through a charcoal and anion exchange column and a conventional dialyzer. ECAD was associated with improved 30-day survival (PP, 11 of 12 ECAD, 6 of 11 controls; log rank P <.05). Plasma bile acids and bilirubin decreased on average by 43% and 29%, respectively, in the ECAD group after 1 week of treatment, but not in the control group. Renal dysfunction and hepatic encephalopathy improved in the ECAD group, but worsened significantly in the control group. ECAD was safe, with adverse events being rare and identical in both groups. In conclusion, ECAD appears to be effective and safe for the short-term treatment of patients with cirrhosis and superimposed acute injury associated with progressive hyperbilirubinemia and may be useful for increasing survival in such patients awaiting liver transplantation.",
"Patients with severe acute alcoholic hepatitis develop multiple organ failure which is associated with production of inflammatory cytokines and a poor prognosis. The aim of the present pilot study was to evaluate the effects of the BioLogic-DT sorption-suspension dialyser in patients with severe acute alcoholic hepatitis. Ten patients with encephalopathy (grade II-IV) were entered into the study, 5 received treatment with the BioLogic-DT for 6 hours daily for 3 days and 5 received conventional treatment as controls. The system was biocompatible with no adverse effects on blood pressure or platelet counts, factor V, fibrinogen or antithrombin III. No bleeding episodes were observed even with the use of small doses of heparin. After 3 days, blood ammonia was lower in the BioLogic-DT treated patients than in the controls, although blood lactate was higher. There were slight increases in plasma TNF and IL-8 during treatment over and above the higher levels present initially, possibly as a result of activation of white cells in the extracorporeal circuit. The further development of the BioLogic-DT dialyser with the addition of a plasma treatment module capable of removing cytokines would be worth evaluating in acute alcoholic hepatitis.",
"Poor nutritional status is common among patients awaiting orthotopic liver transplantation and is associated with poor outcome.\n This prospective randomized controlled trial examined the effect of pretransplant nutritional supplementation on the outcome of patients undergoing liver transplantation. Of 82 consecutive patients with mid-arm muscle circumference <25th percentile, 42 received enteral supplementation, and the remainder acted as the control group. The supplemented group received a calorie-dense enteral feed taken daily (in addition to diet) until transplantation. Nutritional status was monitored by upper arm anthropometric measurements and handgrip strength. Dietary intake was calculated from 5-day food diaries.\n Supplementation improved mid-arm circumference, mid-arm muscle circumference, and grip strength. Pretransplant nutritional status was not associated with posttransplant sepsis or major complications. Preoperative grip strength of <85% of normal values was predictive of increased incidence of posttransplant major complications. Supplementation did not affect outcome, although there were more deaths in the control group (seven deaths before and two deaths after transplant) than there were in the supplemented group (two deaths before and three deaths after transplant). There was no difference in overall survival (P = 0.075).\n Enteral supplementation improved some parameters of nutritional status pretransplant. Dietary intake of patients in the two groups was similar at transplant. Nutritional supplementation has not increased nutritional intake, although this may reflect the importance of regular dietetic input and support, rather than suggesting that nutritional supplementation is ineffective. Supplementation had no effect on outcome of liver transplantation.",
"Oxidative stress is putatively involved in the pathogenesis of alcohol-induced liver injury. This trial was devised to determine whether antioxidant therapy, alone or as an adjunct to corticosteroids, improved survival in patients with acute alcoholic hepatitis.\n Patients with a severe alcoholic hepatitis were stratified by sex and steroid use, and then randomized. The active group received N-acetylcysteine for one week, and vitamins A-E, biotin, selenium, zinc, manganese, copper, magnesium, folic acid and Coenzyme Q daily for 6 months. The trial was double blinded and placebo controlled. The primary end-point was mortality within 6 months.\n Thirty-six (20 male, 16 female; mean discriminant function (DF) 86.6) received active drug, and 34 (18 male, 16 female; mean DF 76.4) received placebo. 180-day survival was not significantly different between patients receiving drug and placebo (52.8% vs. 55.8%, p=0.699). This was not affected by stratification for steroid use or sex. The only predictors of survival in multivariate analysis were initial bilirubin (p=0.017), white cell count (p=0.016) and age (p=0.037). Treatment allocation did not affect survival in multivariate analysis (p=0.830).\n Antioxidant therapy, alone or in combination with corticosteroids, does not improve 6-month survival in severe alcoholic hepatitis.",
"Nutritional support in patients with advanced cirrhosis is difficult due to protein, fluid and salt restrictions. Successful liver transplantation should improve nutrient tolerance. We randomly assigned 28 hypoalbuminemic cirrhotic patients to receive, immediately after liver transplantation, one of three regimens: group 1, no nutritional support (n = 10); group 2, total parenteral nutrition (TPN) (35 kcal/kg/day) with standard amino acids (1.5 g/kg/day) (n = 8); or group 3, isocaloric isonitrogenous TPN with added branched-chain amino acids (n = 10). Therapy was continued for 7 days posttransplant. Jaundice resolution was unaffected by nutritional support. Nitrogen balance favored both TPN groups. Branched-chain amino acid (BCAA) aromatic amino acid ratios were highest in group 3. Coma scores and serum ammonia levels were similar in all groups. Both TPN groups achieved respirator independence earlier; this difference was not statistically significant. Group 1 patients stayed longest in ICU; the difference was statistically significant. TPN with either standard or BCAA- enriched amino acids is tolerated well immediately after successful liver transplant. Positive nitrogen balance is achieved; large protein loads do not worsen encephalopathy. Nutritional support may improve respiratory muscle function, allowing earlier weaning from ventilatory support. A shortened length of ICU stay justifies the expense of TPN.",
"This prospective study compared the effects of tube-fed nutrition with those of a regular diet in alcoholic liver disease. The high prevalence of malnutrition in patients with alcoholic liver disease requires clarification of the benefits of aggressive nutritional support. Patients were randomly assigned a regular diet without or with tube-fed supplementation, delivering 1.5 g/kg protein and 167 kJ/kg daily. Comparisons of encephalopathy, antipyrine clearance, metabolic rate, and biochemical parameters were performed weekly for 4 weeks. Sixteen patients receiving enteral supplementation had antipyrine half-life (50% vs. 3% reduction), serum bilirubin (25% vs. 0% reduction), and median encephalopathy scores that improved more rapidly than those of controls. Initially, 15 controls did not consume adequate calories to meet measured resting energy expenditure. Aggressive nutritional intervention accelerated improvement in alcoholic liver disease. Adverse effects did not offset the demonstrated benefits of a 2-cal/mL, casein-based tube-fed supplement. These findings support the use of standard, casein-based solutions in the treatment of alcoholic liver disease and as the control condition for future studies.",
"A double-blind placebo-controlled trial of intravenous prostaglandin PGE1 (40 micrograms/h) was conducted in adult orthotopic liver transplant recipients. Infusion was started intraoperatively and continued for up to 21 days. Patients were followed up for 180 days postoperatively. Among 172 patients eligible for treatment in the study, 160 could be evaluated (78 PGE1; 82 placebo). Patient and graft survival were similar (PGE1: 16 deaths, 9 retransplantations [7 survivors]; controls: 15 deaths, 6 retransplantations [3 survivors]). In patients with surviving grafts, however, PGE1 administration resulted in a 23% shorter mean duration of hospitalization following transplantation (PGE1: 24.4 days; controls: 31.8 days; P = .02) and a 40% shorter length of time postoperatively in the intensive care unit (PGE1: 8.2 days; controls 13.7 days; P = .05). Reduced needs for renal support (P = .03) or surgical intervention other than retransplantation (P = .02) were also noted with PGE1 use. Further, PGE1 administration resulted in a trend toward improved survival rates in patients with mild renal impairment (preoperative serum creatinine 1.5 mg percent or greater; P = .08). Neither the incidence of acute cellular rejection nor of primary nonfunction was significantly different in the two groups. Phlebitis was the only complication that was more common during PGE1 administration, (PGE1: 9; controls: 4). These results suggest that PGE1 use in hepatic allograft recipients reduces morbidity and may result in sizable cost reductions.",
"Acute renal failure occurring immediately after liver transplantation and requiring hemodialysis is a major problem resulting in a poor prognosis. We investigated the efficacy of human atrial natriuretic peptide, which has potent natriuretic effects and unique protective effects for glomeruli in preventing acute renal failure after liver transplantation.\n Thirty-seven patients who underwent live donor liver transplantation with model for end-stage liver disease scores greater than 15 were the subjects of the study. Subjects were prospectively randomized into two groups: patients that received synthetic human atrial natriuretic peptide infusion (Group H: n=19) and those that received conventional diuretics, furosemide and potassium canrenoate (Group C: n=18). The peri- and postoperative changes in hemodynamic status and renal function were compared between the two groups.\n There were no statistical differences in the changes in hemodynamic status between groups. Hemodialysis was required after liver transplantation in nine patients, two in Group H and seven in Group C (P=0.04). Postoperative creatinine clearance was higher in Group H (P=0.03). Aldosterone level was suppressed in group H (P=0.006).\n Continuous infusion of synthetic human atrial natriuretic peptide might be effective for preventing acute renal failure requiring hemodialysis after liver transplantation.",
"We performed a controlled trial of peripheral hyperalimentation in moderate and severe alcoholic hepatitis to determine whether improvement in survival and liver function could be obtained. Twelve patients with moderate and 22 with severe alcoholic hepatitis were randomized to 28 days of peripheral parenteral nutrition (PPN) or standard therapy (ST). In the moderate group, six were treated with each therapy. In the severe group, 10 were treated with PPN and 12 with ST. Routine liver tests, hepatocyte function (galactose elimination capacity), estimated hepatic blood flow (galactose clearance) and assessment of ascites and encephalopathy were performed at randomization and at 28 days. Groups were equally matched at randomization. In the moderate group PPN produced no improvement in morbidity (liver tests) and mortality (no deaths). In the severe group there were seven deaths (4 PPN, 3 ST). PPN produced greater improvement than ST in serum bilirubin and transferrin concentrations and a trend toward greater improvement in prothrombin time, serum albumin and galactose elimination capacity. PPN had no deleterious effect on encephalopathy or ascites as only ST patients developed ascites or encephalopathy after randomization. We conclude that PPN compared to ST (1) provides no benefit in moderate alcoholic hepatitis, but (2) did more rapidly improve morbidity (liver tests) and probably liver function in severe alcoholic hepatitis; (3) PPN did not improve early mortality, and (4) it had no deleterious effect on encephalopathy or ascites.",
"Resection of hepatocellular carcinoma is associated with high rates of morbidity and mortality. Since intensive nutritional support can reduce the catabolic response and improve protein synthesis and liver regeneration, we performed a prospective study to investigate whether perioperative nutritional support could improve outcome in patients undergoing hepatectomy for hepatocellular carcinoma.\n We studied 124 patients undergoing resection of hepatocellular carcinoma. Sixty-four patients (39 with cirrhosis, 18 with chronic active hepatitis, and 7 with no associated liver disease) were randomly assigned to receive perioperative intravenous nutritional support in addition to their oral diet, and 60 patients (33 with cirrhosis, 12 with chronic active hepatitis, and 15 with no associated liver disease) were randomly assigned to a control group. The perioperative nutritional therapy consisted of a solution enriched with 35 percent branched-chain amino acids, dextrose, and lipid emulsion (50 percent medium-chain triglycerides) given intravenously for 14 days perioperatively.\n There was a reduction in the overall postoperative morbidity rate in the perioperative-nutrition group as compared with the control group (34 percent vs. 55 percent; relative risk, 0.66; 95 percent confidence interval, 0.45 to 0.96), predominantly because of fewer septic complications (17 percent vs. 37 percent; relative risk, 0.57; 95 percent confidence interval, 0.34 to 0.96). There were also a reduction in the requirement for diuretic agents to control ascites (25 percent vs. 50 percent; relative risk, 0.57; 95 percent confidence interval, 0.37 to 0.87), less weight loss after hepatectomy (median loss, 0 kg vs. 1.4 kg, P = 0.01), and less deterioration of liver function as measured by the change in the rate of clearance of indocyanine green (-2.8 percent vs. -4.8 percent at 20 minutes, P = 0.05). These benefits were seen predominantly in the patients with underlying cirrhosis who underwent major hepatectomy. There were five deaths during hospitalization in the perioperative-nutrition group, and nine in the control group (P not significant).\n Perioperative nutritional support can reduce complications after major hepatectomy for hepatocellular carcinoma associated with cirrhosis.",
"To assess the immediate and long-term effects of ischemic preconditioning (IPC) in deceased donor. liver transplantation (LT), we designed a prospective, randomized controlled trial involving 60 donors: control group (CTL, n = 30) or study group (IPC, n = 30). IPC was induced by 10-min hiliar clamping immediately before recovery of organs. Clinical data and blood and liver samples were obtained in the donor and in the recipient for measurements. IPC significantly improved biochemical markers of liver cell function such as uric acid, hyaluronic acid and Hypoxia-Induced Factor-1 alpha (HIF-1 alpha) levels. Moreover, the degree of apoptosis was significantly lower in the IPC group. On clinical basis, IPC significantly improved the serum aspartate aminotransferase (AST) levels and reduced the need for reoperation in the postoperative period. Moreover, the incidence of primary nonfunction (PNF) was lower in the IPC group, but did not achieve statistical significance. We conclude that 10-min IPC protects against I/R injury in deceased donor LT.",
"Twenty-eight patients with biopsy or clinical acute alcoholic hepatitis were prospectively randomized to 21 days of conventional therapy (14 control patients) or, in addition, to 2 L/day of a peripheral iv infusion of a 900 mosmol amino acid-glucose solution (14 patients). Cirrhosis was present in 64% of controls and in 54% of infused patients. There were three deaths in controls and one in the infused group. There were no significant intergroup differences in mortality, clinical findings, liver tests, or functional mass by the galactose elimination capacity either at entry or after completion of the study. In controls, there was intragroup improvement in serum bilirubin (p = 0.033) and AST (p = 0.008) but not in other \"liver tests\" or in functional hepatic mass by galactose elimination capacity. In infused patients there was improvement in bilirubin (p = 0.001), AST (p = 0.008), and serum albumin (p = 0.016). Improvement in functional mass by galactose elimination capacity was significant at the p = 0.052 level. Hyaline was initially present in six of eight pairs of biopsies in both groups. After treatment, five of six pairs in controls but only one of six pairs in the infused group still had hyaline (p = 0.03). This latter finding, if confirmed in larger groups, may be of considerable clinical importance. It is suggested that 3- to 4-wk trials of such protocols may require a longer duration of follow-up in greater numbers of patients to detect important advantages of amino acid-glucose infusions which are only implicit in these findings."
] |
This Review indicates that artificial support systems may reduce mortality in acute-on-chronic liver failure. Artificial and bioartificial support systems did not appear to affect mortality in acute liver failure. However, considering the strength of the evidence additional randomised clinical trials are needed before any support system can be recommended for routine use.
|
CD000511
|
[
"8516091",
"2000109",
"9120744",
"2007937",
"10021717",
"2187176",
"2117205"
] |
[
"Prophylactic administration of calf lung surfactant extract is more effective than early treatment of respiratory distress syndrome in neonates of 29 through 32 weeks' gestation.",
"A comparison of surfactant as immediate prophylaxis and as rescue therapy in newborns of less than 30 weeks' gestation.",
"Prophylaxis of respiratory distress syndrome by treatment with modified porcine surfactant at birth: a multicentre prospective randomized trial.",
"Randomized, placebo-controlled trial of human surfactant given at birth versus rescue administration in very low birth weight infants with lung immaturity.",
"Use of surfactant for prophylaxis versus rescue treatment of respiratory distress syndrome: experience from an Italian-Bulgarian trial.",
"Multicenter trial of single-dose modified bovine surfactant extract (Survanta) for prevention of respiratory distress syndrome. Ross Collaborative Surfactant Prevention Study Group.",
"A multicenter randomized controlled clinical trial of bovine surfactant for prevention of respiratory distress syndrome."
] |
[
"Although numerous trials have demonstrated the efficacy of exogenous surfactant for prophylaxis or treatment of neonatal respiratory distress syndrome (RDS), optimum timing of administration remains controversial. One previous study showed that administration of calf lung surfactant extract immediately following birth, to neonates born before 30 weeks postconceptional age, was preferable to delaying administration until after development of RDS. The current study was designed to test a similar hypothesis for babies born between 29 and 32 weeks gestational age.\n One thousand three hundred ninety-eight neonates with obstetric estimates of 29 through 32 weeks' gestation were randomized to receive CLSE at birth or to wait until development of mild RDS. After exclusions for malformations and other factors, data from 1248 were analyzed.\n Prophylaxis was associated with less development of moderate RDS (7% vs 12%), less need for retreatment (5% vs 9%), less need for mechanical ventilation or supplemental oxygen during the first 4 days, and fewer deaths or less requirement for supplemental oxygen at 28 days (5% vs 9%). Although 1-minute Apgar scores were significantly lower in the prophylaxis group, the difference disappeared by the 5-minute score and there was no difference in the incidence of asphyxia-related complications. Sixty percent of the neonates assigned to early treatment received endotracheal intubation and 43% received calf lung surfactant extract at a median age of 1.5 hours. When data were analyzed by gestational age and birth weight subgroups, most of the differences could be attributable to babies born at 30 weeks or less or weighing less than 1500 g, probably because of the higher incidence of surfactant deficiency in this more immature subgroup.",
"Exogenous pulmonary surfactants are administered into the trachea either to prevent respiratory distress syndrome in premature infants or to treat it. In a randomized, multicenter trial, we compared the results of surfactant therapy initiated as prophylaxis with the results of rescue therapy with surfactant.\n Before birth, 479 infants with an estimated gestational age of less than 30 weeks were randomly assigned to receive surfactant as prophylaxis (n = 235) or rescue therapy (n = 244). The infants in the prophylaxis group received a 90-mg intratracheal dose of an exogenous calf-lung surfactant extract at the time of delivery, whereas the infants in the rescue-therapy group received 90 mg of the surfactant several hours after delivery if the fractional inspiratory oxygen concentration was at least 0.40 or if the mean airway pressure was at least 0.686 kPa (7 cm of water), or both. Infants in both groups received additional doses of surfactant at intervals of 12 to 24 hours if these criteria were met.\n The proportion of infants surviving until discharge to their homes was significantly higher in the prophylaxis group than in the rescue-therapy group (88 vs. 80 percent, P = 0.028). This difference was due primarily to the longer survival of very premature infants (less than or equal to 26 weeks' gestation) in the prophylaxis group than in the rescue-therapy group (75 vs. 54 percent, P = 0.006). According to proportional-hazards regression analysis, the distribution of survival times was better for all infants in the prophylaxis group (P = 0.007) and for the subgroup of infants in the prophylaxis group who were delivered at 26 weeks' gestation or earlier (P = 0.0048). Infants in the prophylaxis group who were delivered at 26 weeks' gestation or earlier had a lower incidence of pneumothorax than similar infants in the rescue-therapy group (7 vs. 18 percent, P = 0.03).\n We found a significant advantage to the administration of the initial dose of surfactant as prophylaxis rather than as rescue therapy in very premature infants.",
"The objective of this prospective, multicentre trial, carried out at 18 third level hospitals in Italy, was to evaluate efficacy of modified porcine surfactant (Curosurf), administered at birth to prevent the development of respiratory distress syndrome (RDS) in premature infants. 287 babies with a gestational age of 24-30 weeks were randomized to prophylactic treatment with Curosurf (80 mg/ml; dose 20 mg/kg) or to a control group receiving no surfactant treatment in the delivery-room. Babies in both groups were eligible for rescue treatment with surfactant (200 mg/kg) if they developed clinical symptoms of RDS and required mechanical ventilation. The main end-point was to obtain, in the prophylaxis group, a 30% reduction in the incidence of grade 3-4 RDS. Median gestational age was 28 weeks in both groups and mean birth weight 1010 and 1002 g, respectively for prophylaxis and control babies. There was a 32% reduction in the incidence of grade 3-4 RDS in the prophylaxis group (p < 0.05). This was associated with a significant reduction in mean maximum fraction of inspired oxygen (0.57 vs 0.66%; p < 0.01), a decreased incidence of pulmonary interstitial emphysema (7 vs 14%; p < 0.05) and a lowered mortality (21 vs 35%; p < 0.01). Combined unfavourable outcome (mortality + bronchopulmonary dysplasia and/or grade 3-4 intraventricular hemorrhage and/or grade 2-4 retinopathy of prematurity) was significantly lower in the prophylaxis than in the second group (41 vs 58%; p < 0.01). The favourable effects of prophylactic treatment were equally recorded in all the age groups, including the babies with the lowest gestational age (24-25 weeks). Multiple and logistic regression analysis confirmed that high gestational age and surfactant prophylaxis were, independently, associated with a lower degree of RDS (p = 0.0001 and p = 0.0008, respectively) and a lower mortality (p = 0.0001 and p = 0.0045, respectively). We conclude that prophylaxis with modified natural surfactant effectively prevents RDS in newborn babies between 24 and 30 weeks' gestation.",
"A randomized, placebo-controlled trial of human surfactant given intratracheally at birth (prophylactic) versus rescue administration after the onset of severe respiratory distress syndrome (RDS) was conducted among preterm infants born at 24 to 29 weeks of gestation. Singleton fetuses were randomly assigned to receive (1) placebo (air), (2) prophylactic surfactant treatment, or (3) rescue surfactant treatment; infants of multiple births received either (1) prophylactic or (2) rescue treatment. Of 282 potentially eligible fetuses, 246 infants received treatments at birth and 200 infants had RDS. Outcomes are presented both as an intention-to-treat analysis (including infants who met exclusion criteria at or after birth) and as a full treatment protocol analysis for those infants with RDS and likely to benefit from surfactant. Preterm infants (mean 1.0 kg birth weight, 27 to 28 weeks of gestational age) randomly assigned to receive prophylactic treatment received surfactant soon after birth; those assigned to receive rescue surfactant had instillation at a mean age of 220 minutes if the lecithin-sphingomyelin ratio was less than or equal to 2.0 and no phosphatidylglycerol was detected in either amniotic fluid or initial airway aspirate, oxygen requirements were a fraction of inspired oxygen of greater than 0.5, and mean airway pressure was greater than or equal to 7 cm H2O from 2 to 12 hours after birth. Up to four treatment doses (or air) were permitted within 48 hours; approximately 60% of surfactant-treated infants required two or more doses. Surfactant-treated infants had significantly less pulmonary interstitial emphysema than placebo-treated infants (p = 0.02), but there were no other significant differences in mortality rates or morbidity. Indexes of oxygenation and ventilation were improved in surfactant recipients during the first 24 hours. An intention-to-treat analysis found no significant differences between infants given placebo and surfactant-treated infants or between prophylactic- and rescue-treated infants; an improved total mortality rate (p = 0.002) was found among surfactant-treated infants in Helsinki but not in San Diego. Among infants with RDS, the total mortality rate was significantly improved (p = 0.004) with surfactant treatment but not the proportion alive and without bronchopulmonary dysplasia at 28 days (p = 0.052), or the proportion alive and without bronchopulmonary dysplasia at 38 weeks of postconceptional age (p = 0.18) to adjust for differences in prematurity. Deaths caused by RDS or bronchopulmonary dysplasia were significantly reduced among surfactant recipients (p = 0.0001). Neither among singletons nor among multiple-birth infants was there a selective advantage to prophylactic versus rescue treatment.(ABSTRACT TRUNCATED AT 400 WORDS)",
"To show if surfactant applied in different social-sanitary realities as prophylaxis of respiratory distress syndrome (RDS) is equally useful and able to reduce mortality and incidence of 3-4 radiological grade RDS.\n Two neonatal intensive care units (NICU) in Italy, one NICU in Bulgaria and one NICU in Romania were involved in a randomized controlled clinical trial of prophylaxis vs rescue treatment of RDS. Babies with gestational age 26-30 wks were randomized before birth to prophylaxis in the delivery-room with 200 mg/kg of porcine surfactant (prophylaxis) or to routine assistance (control). Subsequently the babies developing RDS requiring mechanical ventilation and fraction of inspired oxygen (FiO2) > or = 0.4 to maintain PaO2 about 50 mmHg were allowed to be treated rescue with 200 mg/kg of the same surfactant. To reach end-points of reducing mortality by 40% and incidence of radiological grade 3-4 RDS a total number of 174 patients were required.\n Due to logistic, practical and social-political problems the study was interrupted after enrollment of 93 babies (61 in Italy and 32 in Bulgaria). The Romanian centre did not start the study because it was impossible in the scheduled times to equip it for mechanical ventilation of the newborn infants. Analysis done on an intention to treat basis did not show significant reductions of mortality and 3-4 radiological grade RDS, even if there was a trend towards a reduction in the babies given prophylaxis. A significantly lower number of babies given prophylaxis required a subsequent rescue treatment compared to controls (p < 0.001). There was no difference in other complications such as intraventricular haemorrhage, air-leak syndromes and infections between prophylaxis and control infants. As regards pulmonary gas exchange, the PaO2/FiO2 ratio was significantly improved in the babies given prophylaxis for the first 12 hours of life vs the controls.\n Even if the study was terminated before term, the analysis of the data shows that prophylaxis with surfactant is equally effective in different social-clinical conditions to improve pulmonary gas-exchange, especially in the first critical hours of life of premature babies.",
"A multicenter, prospective randomized controlled trial was performed comparing the efficacy of a single intratracheal dose of modified bovine surfactant extract (Survanta, 100 mg/kg, Abbott Laboratory, North Chicago, IL) with air placebo in preventing respiratory distress syndrome. Infants were enrolled if they were estimated to be between 24 and 30 weeks' gestation, weighed between 750 and 1250 g, and were intubated and stabilized within 15 minutes after birth. A total of 160 infants were treated (79 with surfactant, 81 with air placebo) between 4 and 37 minutes after birth (median time 12 minutes). Of these, 5 infants were excluded from the final analysis. The 72-hour average values for the arterial-alveolar oxygen ratio, fraction of inspired oxygen, and mean airway pressure were calculated from the area under the curve of scheduled values measured throughout 72 hours. Clinical status was classified using five ordered categories (no supplemental oxygen or assisted ventilation, supplemental oxygen only, continuous positive airway pressure or assisted ventilation with intermittent mandatory ventilation less than or equal to 6 breaths/min, assisted ventilation with intermittent mandatory ventilation greater than 6 breaths/min, death). Chest radiographs at 24 hours were graded for severity of respiratory distress syndrome. Infants receiving Survanta had less severe radiographic changes at 24 hours of age and decreased average fraction of inspired oxygen (31% vs 42%, P = .002) compared with control infants. No differences were noted in the average arterial-alveolar oxygen ratio, mean airway pressure, or clinical status on days 7 and 28. A beneficial effect was noted in the incidence of pneumothorax (P = .057) and an increase was noted in the incidence of necrotizing enterocolitis (P = .052). No differences in incidence of patent ductus arteriosus, intraventricular hemorrhage, sepsis, or bronchopulmonary dysplasia were seen. According to results of a secondary analysis, there was improvement in the fraction of inspired oxygen and a greater number of survivors without bronchopulmonary dysplasia in the subgroup of infants weighing less than 1000 g who were treated with surfactant. It was concluded that a single dose of Survanta given shortly after birth resulted in decreased severity of chest radiographic findings 24 hours after treatment and improved oxygenation during 72 hours after treatment, but did not improve other acute measures of disease severity or clinical status later in the neonatal period. The group at highest risk for respiratory distress syndrome (infants with birth weights between 750 and 999 g) may benefit the most from preventive therapy.",
"Treatment with bovine surfactant (SF-RI 1) was shown to be efficacious in improving pulmonary function and in increasing survival rate without BPD in very premature infants. Surfactant therapy did not affect the risk of major complications of prematurity."
] |
Prophylactic intratracheal administration of animal derived surfactant extract to infants judged to be at risk of developing respiratory distress syndrome has been demonstrated to improve clinical outcome. Infants who receive prophylactic animal derived surfactant extract have a decreased risk of pneumothorax, a decreased risk of PIE, a decreased risk of mortality, and a decreased risk of BPD or death.
|
CD006319
|
[
"12473883",
"16007352",
"10344682",
"15543373",
"14972218",
"15368794",
"12548410",
"9407981",
"12972959",
"10668875",
"11878300",
"3554492",
"8969668",
"11875680"
] |
[
"A randomized, controlled trial of fibrin glue vs. conventional treatment for anal fistula.",
"Controlled, randomized trial of island flap anoplasty for treatment of trans-sphincteric fistula-in-ano: early results.",
"Repair of fistulas-in-ano using autologous fibrin tissue adhesive.",
"Radiofrequency fistulotomy: a better alternative for treating low anal fistula.",
"Radiosurgical fistulotomy; an alternative to conventional procedure in fistula in ano.",
"Radiofrequency fistulectomy vs. diathermic fistulotomy for submucosal fistulas: a randomized trial.",
"Randomized clinical trial comparing simple drainage of anorectal abscess with and without fistula track treatment.",
"Randomized controlled trial of primary fistulotomy with drainage alone for perianal abscesses.",
"Efficacy of fibrin sealant in the management of complex anal fistula: a prospective trial.",
"Repair of chronic anorectal fistulae using commercial fibrin sealant.",
"Preliminary results of using a commercial fibrin sealant in the treatment of fistula-in-ano.",
"A randomized trial of fistulotomy in perianal abscess.",
"Prospective randomized trial of drainage alone vs. drainage and fistulotomy for acute perianal abscesses with proven internal opening.",
"Prospective randomised trial comparing ayurvedic cutting seton and fistulotomy for low fistula-in-ano."
] |
[
"Fibrin glue is a novel treatment for anal fistulas and possesses many advantages in the treatment of difficult high fistulas. Fibrin glue treatment is simple and repeatable; failure does not compromise further treatment options; and sphincter function is preserved. We aimed to compare the outcomes of patients with low and high anal fistulas randomly assigned to either fibrin glue or conventional treatment.\n Patients with simple fistulas (low fistulas) and complex fistulas (high, Crohn's, and low fistulas with compromised sphincters) were randomly assigned to either fibrin glue or conventional treatment (fistulotomy or loose seton insertion with or without subsequent advancement flap). Patients with rectovaginal fistulas and anal fistulas associated with chronic cavities, acute sepsis, and side branches were excluded. The primary end point was fistula healing. Secondary end points were complications, changes in preoperative continence score, changes in maximum resting and squeeze pressure, satisfaction scores, and pain scores and time off work (simple fistulas only).\n Patients in the fibrin glue and conventional treatment arms were well matched for gender, median age, duration of fistula symptoms, and follow-up. Fibrin glue healed three (50 percent) of six and fistulotomy seven (100 percent) of seven simple fistulas (difference, 50 percent; confidence interval, 10 to 90 percent; P= 0.06, Fisher's exact probability test). There was no change in baseline incontinence score, maximum resting pressures, or squeeze pressures between the study arms. Return to work was quicker in the glue arm, but pain scores were similar and satisfaction scores higher in the fistulotomy group. Fibrin glue healed 9 (69 percent) of 13 and conventional treatment 2 (13 percent) of 16 complex fistulas (difference, 56 percent; 95 percent confidence interval, 25.9 to 86.1 percent; P= 0.003, Fisher's exact probability test). There was no change in baseline incontinence score, maximum resting pressures, or squeeze pressures in either study arm. Satisfaction scores were higher in the fibrin glue group.\n No advantage was found for fibrin glue over fistulotomy for simple fistulas, but fibrin glue healed more complex fistulas than conventional treatment and with higher patient satisfaction.",
"Treatment of trans-sphincteric fistula is usually a compromise between recurrence and incontinence. Dermal island flap anoplasty has been found to be useful in the treatment of these fistulas. We performed a randomized trial to compare dermal island flap anoplasty with conventional treatment for trans-sphincteric fistula-in-ano. Seventy nine patients with fistula-in-ano were recruited; twenty patients with trans-sphincteric fistula confirmed by endoanal ultrasound were prospectively randomized to receive either dermal island flap anoplasty (IFA) or conventional treatment (CVN) for trans-sphincteric fistula-inano. Conventional treatment consisted of lay open fistulotomy or seton insertion if deemed unsuitable for fistulotomy. Dermal island flap anoplasty involved a cutaneous advancement flap into the rectum. Pain scores, fecal incontinence scores, operative complications, wound healing and recurrence rates were charted. Two patients in the CVN group required seton insertions, which were still intact at the 9-month follow-up. Two patients with similar high trans-sphincteric fistula in the IFA group avoided having a long-term seton. There were no differences in the postoperative pain score, incontinence score, complications, wound healing and recurrence rates between the two groups. IFA is a safe and useful method for treating transsphincteric fistula. It can be considered when a suprasphincteric extension is suspected, thus avoiding risk of incontinence or the discomfort of a long-term seton.",
"Our goal was to determine if autologous fibrin tissue adhesive derived from the precipitation of fibrinogen using a combination of ethanol and freezing, could be used to completely close both simple and complex fistulas-in-ano.\n A 26-patient pilot study was performed in which 100 ml of a patient's blood was drawn 90 minutes before surgery. Autologous fibrin tissue adhesive was prepared. In the operating room the patient underwent an examination under anesthesia, and the primary and secondary fistula tract openings were attempted to be identified. The fistula tract was curetted, and autologous fibrin tissue adhesive was injected into the secondary fistula tract opening until fibrin glue was seen coming from the primary opening. A petroleum jelly gauze was then applied over the secondary opening, and the patient was sent home. Follow-up visits were scheduled for one week, one month, three months, and one year later.\n Twenty-six patients received autologous fibrin tissue adhesive fistula injections, with a mean follow-up of 3.5 months. Initial results were encouraging. Twenty-one of 26 patients (81 percent) had successful initial closure of their fistulas. Two of five failures were injected a second time, and one closed, giving an overall successful closure rate of 85 percent (22/26 patients). Of five patients who failed, mean time to failure was 3.8 weeks. In addition, there was no evidence of infection or complications related to the procedure.\n Our initial results are optimistic and require further support through longer follow-up data. Fibrin glue treatment of anorectal fistulas offers a unique mode of management that is safe, simple, and easy for the surgeon to perform. By using autologous fibrin tissue adhesive the patient avoids the risk of anal incontinence and the discomfort of prolonged wound healing which may be associated with fistulotomy.",
"Wide varieties of approaches are employed in dealing with low anal fistula. However, the simple method of laying open the fistula tract (fistulotomy) is still considered to be the favored one.\n A modified approach to the procedure of fistulotomy is discussed. This study describes the procedure, which used a technique of radiofrequency surgery, and its outcome in 232 patients with low anal fistula. The patients were followed for a period of 15 months.\n The patients were discharged on the same day as the procedure. The mean period off work was four days. The average healing time recorded was 67 days. Four wound complications in the form of premature closure of the external wound were noted, which required trimming of the edges. Two of these wounds remained unhealed. The recurrence rate was 1.7%.\n In this era when the emphasis is on criteria like the minimization of hospital stay, reduction of postoperative pain, early resumption of work and low and comparable recurrence rates, there is a future for the procedure of radiofrequency fistulotomy.",
"Most surgeons continue to prefer the classic lay open technique [fistulotomy] as the gold standard of treatment in anal fistula. In this randomized study, a comparison is made between conventional fistulotomy and fistulotomy performed by a radio frequency device.\n One hundred patients of low anal fistula posted for fistulotomy were randomized prospectively to either a conventional or radio frequency technique. Parameters measured included time taken for the procedure, amount of blood loss, postoperative pain, return to work, and recurrence rate.\n The patient demographic was comparable in 2 groups. The radio frequency fistulotomy was quicker as compared to a conventional one [22 versus 37 minutes, p = 0.001], amount of bleeding was significantly less [47 ml versus 134 ml, p = 0.002], and hospital stay was less when patient was operated by radio frequency method [37 hours versus 56 hours in conventional method, p = 0.001]. The postoperative pain in the first 24 hours was more in conventional group [2 to 5 versus 0 to 3 on visual analogue scale]. The patients from radio frequency group resumed their duties early with a reduced healing period of the wounds [47 versus 64 days, p = 0.01]. The recurrence or failure rates were comparable in the radio frequency and conventional groups [2% versus 6%].\n Fistulotomy procedure using a radio frequency technique has significant advantages over a conventional procedure with regard to operation time, blood loss, return to normal activity, and healing time of the wound.",
"Anal fistula represents one of the most frequent anorectal disease. Fistulotomy is considered the gold standard treatment but related problems are numerous (postoperative pain, bleeding, delayed or impaired wound healing). Fistulectomy lowers the recurrences but is less feasible with longer operating time and healing process. We applied the radiofrequencies to fistulectomy and compared the early and late results with those obtained from traditional fistulotomy.\n Twenty patients were randomized to undergo radiofrequency fistulectomy (10 patients, Group A) or conventional fistulotomy (10 patients, Group B). We analysed the first postoperative day pain, intra- and postoperatory bleeding, operating time, complications (impaired or delayed wound healing, fecal incontinence) and any recurrences.\n The mean values for operative time have been 18.3 min for group A (range 15-26 min) and 17.9 min for group B (range 13-21 min). According to VAS scale, first postoperative day pain mean values were 2.8 for group A (range 2-4) and 4.1 for group B (range 3-5). Intra- and post-operative bleeding has always been negligible and faecal incontinence was never observed. Healing time mean values have been 3.5 weeks for group A (range 3-5) and 5.9 weeks for group B (range 4-8 weeks). Long-term results did not evidence complications or recurrences for both groups.\n The application of radiofrequencies to fistulectomy renders more feasible and easies the operation. Postoperative pain is smaller than traditional fistulotomy because of the lower temperatures used and for the shorter time spent in coagulating. This gives a faster wound healing. In conclusion we think that radiofrequency fistulectomy is technically more advantageous than traditional fistulotomy and furnishes better results.",
"Anal abscess is a frequent acute proctological disorder and whether the underlying fistula should be treated at the same time when the abscess is drained remains controversial. We examined indications for drainage alone versus drainage plus fistulotomy in terms of recurrence and continence.\n We carried out a randomized prospective study of 200 consecutive patients with anal abscess. One group received drainage alone, while in the other group drainage plus fistulotomy was performed when a subcutaneous-mucosa, low transsphincteral, or intersphincteral fistula was found. Delayed progressive fistulotomy with suture threads was performed in cases of high transsphincteric or suprasphincteric fistula.\n The internal opening of the fistula track was found in 83% of the patients. The recurrence rate was related to the surgical technique employed: 29% in the group with drainage alone and 5% in the group for which treatment of the fistula track was attempted. The incontinence rate was also related to the surgical option. In those receiving drainage and treatment of the fistula track incontinence was restricted mostly to patients with delayed fistulotomy (36.7%), compared to 2.8% of patients when simple fistulotomy was performed. There was no incontinence in the drainage alone group.\n Drainage of anal abscess with fistulotomy can be safely performed in cases of subcutaneous, intersphincteral, or low transsphincteral fistulae with a minimal recurrence rate. However, drainage alone and posterior treatment of the fistula track is recommended for high transsphincteral or suprasphincteral fistulae.",
"Primary fistulotomy may be advantageous for perianal abscesses because unlike ischiorectal abscesses, fistulas are more commonly found and can be laid open with full preservation of the external anal sphincters. Therefore, a randomized, controlled trial was conducted to compare primary fistulotomy with incision and drainage alone, specifically for perianal abscesses.\n Fifty-two consecutive patients (43 males; mean age, 40 (standard error of mean, 2) years) with perianal abscesses were randomized to treatment by either incision and drainage (controls; N = 28) or fistulotomy (N = 24). Patients were followed up clinically for a mean of 15.5 (standard error of the mean, 0.7) months. Anorectal manometry was also performed before, six weeks, and three months after surgery.\n Persistent fistulas developing after surgery were significantly more common after incision and drainage (N = 7; 25 percent) than after fistulotomy (N = 0; P = 0.009). One patient in each group was also found to have a residual abscess, which required repeat drainage. All patients remained fully continent. The anal pressures after incision and drainage and fistulotomy were not significantly different. Operative time, hospital stay, and time for the wound to heal completely were the same in both groups.\n Primary fistulotomy at the time of drainage for perianal abscesses results in fewer persistent fistulas and no added risk of fecal incontinence.",
"A prospective trial was conducted to establish long-term healing of complex idiopathic anorectal fistula, without extension, after fibrin glue treatment, with clinical assessment and magnetic resonance imaging to determine tract healing.\n Twenty-two patients undergoing glue instillation after fistula curettage and irrigation were followed up for a median of 14 months. Clinical assessment, short tau inversion recovery sequence magnetic resonance imaging, and combined short tau inversion recovery and dynamic contrast-enhanced magnetic resonance imaging were performed at a median of three months postoperatively, and their ability to predict outcome in the presence of early skin healing was determined.\n Of 22 patients, 19 (86.5 percent) had transsphincteric fistulas, 1 (4.5 percent) had a suprasphincteric fistula, 1 (4.5 percent) had an extrasphincteric fistula, and 1 (4.5 percent) had a rectovaginal fistula. None had clinical or radiologic evidence of secondary extension. Despite skin healing in 17 (77 percent) of 22 patients at a median of 14 days after treatment, only 3 (14 percent) remained healed at 16 months. Magnetic resonance imaging with short tau inversion recovery sequences in combination with dynamic contrast-enhanced magnetic resonance imaging predicted outcome in all 10 assessments (100 percent), compared with short tau inversion recovery sequence alone in 16 (94 percent) of 17 assessments or clinical examination in 12 (71 percent) of 17 (P = 0.02).\n The success rate of fibrin glue application for complex anorectal fistulas without extension is 14 percent. Magnetic resonance imaging predicts outcome at an earlier stage than clinical examination.",
"Commercially produced fibrin sealant can be used to completely close both simple and complex fistulae in ano.\n A 29-patient prospective nonrandomized clinical trial was performed. In the operating room, the patient underwent an examination with anesthesia and the primary and secondary fistula tract openings were attempted to be identified. The fistula tract was curetted and fibrin sealant was injected into the secondary fistula tract opening until fibrin sealant was seen coming from the primary opening. A petroleum jelly gauze was then applied over the secondary opening and the patient was sent home. Follow-up visits were scheduled for 1 week, 1 month, 3 months, and 1 year later.\n Twenty-nine consecutive patients received fibrin sealant injections for their fistulae in ano, with a mean follow-up of 6 months. Two patients had a history of Crohn disease (regional enteritis) and 2 patients had human immunodeficiency virus infection. Overall, 17 (68%) of 25 patients have had successful closure of their fistula with 4 patients lost to follow-up. Two patients required reinjection with fibrin sealant, and neither of these subsequently had closure. One of the 2 patients with Crohn disease had closure, as well as 1 human immunodeficiency virus-positive patient. In addition, there has been no evidence of incontinence or complications related to the use of fibrin sealant in this procedure.\n Initial results in the treatment of chronic anorectal fistulae using commercial fibrin sealant are optimistic, but require further support through longer follow-up data. Fibrin sealant treatment of anorectal fistulae offers a unique mode of management which is safe, simple, and easy for the surgeon to perform. By using fibrin sealant, the patient avoids the risk of fecal incontinence and the discomfort of prolonged wound healing that may be associated with fistulotomy.",
"A prospective non-randomised study fibrin sealant injection to manage patients with fistula-in-ano, with magnetic resonance imaging (MRI) monitoring, was performed during the period 5/6/1999 to 28/2/2000. The aim was to determine whether a fibrin sealant could be used as a treatment modality for anorectal fistula and the usefulness of MRI perineum to monitor the disease activity. Ten patients were included in the study. Mean age was 47 years (range 7 months to 70 years). Male: female ratio was 9:1. Mean follow-up duration was 26.4 weeks. The overall success rate was 60%. The success rate of different fistula types were different (60%, 0%, 100% for intersphincteric, transphincteric, subcutaneous, respectively). Variable decrease in signal on STIR images and contrast enhancement was noted in the patients with successful and failure of fibrin sealant injection. In conclusion, fibrin sealant injection is a useful alternative treatment in the management of fistula-in-ano. MRI is helpful in delineating the anatomy of fistula-in-ano but not a useful tool to follow-up disease activity.",
"In a randomized trial we compared the treatment of perianal abscess by incision only (18 patients) with that by incision followed by fistulotomy 3 days later (20 patients). All patients were observed for 12 months. There were no differences between the two groups with regard to recurrent abscess/fistula, but the fistulotomy group had a statistically significantly higher prevalence of flatus incontinence. Further, fistulotomy was followed by significantly longer duration of hospitalization and by delayed healing. We recommend that fistulotomy is used only in patients with recurrent abscess.",
"Incision and drainage (I & D) with concurrent or delayed fistulotomy is the usual treatment for abscess-fistula with a demonstrated internal opening. We compared incision and drainage alone vs. with concurrent fistulotomy for perianal abscesses with a demonstrated internal opening.\n Consecutive patients with acute perianal abscesses and a demonstrated internal opening were prospectively randomized into either the I & D group or drainage with concurrent fistulotomy group. They were followed up at one month, three months, and one year.\n The I & D group had 21 patients, and the fistulotomy group had 24 patients. Thirteen patients had low intersphincteric abscess-fistula, and seven had low transsphincteric fistulas in the I & D group. The fistulotomy group had 9 intersphincteric abscess-fistula compared with 14 low transsphincteric ones. Median duration of surgery, hospital stay, and continence at final follow-up were the same in the two groups. Three had recurrent abscess-fistula in the I & D group compared with none in the fistulotomy group (P = 0.09).\n I & D alone for acute anal abscess-fistula with demonstrated internal opening showed a tendency to recurrence that did not reach a statistically significant difference compared with concurrent fistulotomy. I & D, therefore, puts only a few patients at risk for recurrence.",
"The aim of this study was to evaluate the role of ayurvedic setons in the treatment of low fistula-in-ano. One hundred and eight patients were randomised into either conventional fistulotomy (F) or ayurvedic cutting seton insertion (C). Endpoints investigated included time to wound healing and complications of surgery. Post-operative pain scores were measured daily using a visual analog scale. Anal function was compared using a continence score. Pre- and postoperative manometry and ultrasound were also performed. After exclusions, there were 54 patients in group F and 46 in group C. There were no differences in age, sex or follow-up duration between the two groups. Healing time was similar between the groups. Group C reported more pain following operation and on the first 2-4 postoperative days, but both groups experienced the same amount of pain subsequently. In conclusion, chemical seton was more painful than conventional fistulotomy in the first few days following surgery. However, there was no difference in time to wound healing, complications or functional outcome."
] |
There are very few randomized controlled trials comparing the various modalities of surgery for fistula in ano. While post operative pain, time to healing and discharge from hospital affect quality of life, recurrence and incontinence are the most important. As it turns out, there seems to be no major difference between the various techniques used as far as recurrence rates are concerned.
The use of Fibrin glue and advancement flaps are associated with low incontinence rates.
There is a crying need for well powered, well conducted randomised controlled trials comparing various modes of treatment of fistula in ano. Newer operations like the anal fistula plug and the LIFT procedure need to be evaluated by randomised clinical trials.
|
CD002738
|
[
"10027430",
"9850359",
"10983616",
"12475833",
"17587425",
"16032934",
"11266239",
"17254760",
"12063520",
"9228354",
"9517598",
"3282826",
"8323451",
"7713201",
"2844548",
"7913155",
"9828851",
"11555383",
"17204317",
"8087329",
"7653745",
"1426202",
"15572534",
"2669554",
"10036345",
"11897984",
"10543286",
"7767512",
"9564977",
"2236929",
"2665584",
"10919682",
"8430924",
"11379810",
"8511727",
"12418582",
"15641629",
"12324672",
"10919681",
"9236507",
"8959118",
"8630590",
"9655732",
"14533658",
"8516087",
"7709992",
"10070568",
"8617079",
"1955002",
"3307881",
"18211118"
] |
[
"Hydrofluoroalkane-134a beclomethasone dipropionate, 400 microg, is as effective as chlorofluorocarbon beclomethasone dipropionate, 800 microg, for the treatment of moderate asthma.",
"Efficacy of chlorofluorocarbon-free beclomethasone dipropionate 400 micrograms day-1 delivered as an extrafine aerosol in adults with moderate asthma.",
"Effectiveness of low doses (50 and 100 microg b.i.d) of beclomethasone dipropionate delivered as a CFC-free extrafine aerosol in adults with mild to moderate asthma. Study Group.",
"Efficacy and safety of beclomethasone dipropionate extrafine aerosol in childhood asthma: a 12-week, randomized, double-blind, placebo-controlled study.",
"Efficacy and safety of inhaled ciclesonide compared with chlorofluorocarbon beclomethasone dipropionate in adults with moderate to severe persistent asthma.",
"Hydrofluoroalkane-134A beclomethasone or chlorofluorocarbon fluticasone: effect on small airways in poorly controlled asthma.",
"Efficacy of HFA-beclomethasone dipropionate extra-fine aerosol (800 microg day(-1)) versus HFA-fluticasone propionate (1000 microg day(-1)) in patients with asthma.",
"Beclometasone dipropionate extrafine aerosol versus fluticasone propionate in children with asthma.",
"Step-down therapy with low-dose fluticasone-salmeterol combination or medium-dose hydrofluoroalkane 134a-beclomethasone alone.",
"A comparison of double-strength beclomethasone dipropionate (84 microg) MDI with beclomethasone dipropionate (42 microg) MDI in the treatment of asthma.",
"Safety and efficacy of fluticasone and beclomethasone in moderate to severe asthma. Belgian Multicenter Study Group.",
"Six-month double-blind, controlled trial of high dose, concentrated beclomethasone dipropionate in the treatment of severe chronic asthma.",
"[Effects of high doses of beclomethasone dipropionate in bronchial asthma].",
"High-dose inhaled steroids in asthmatics: moderate efficacy gain and suppression of the hypothalamic-pituitary-adrenal (HPA) axis. Research Council of the Norwegian Thoracic Society.",
"Effects of inhaled beclomethasone dipropionate on beta 2-receptor function in the airways and adrenal responsiveness in bronchial asthma.",
"Added salmeterol versus higher-dose corticosteroid in asthma patients with symptoms on existing inhaled corticosteroid. Allen & Hanburys Limited UK Study Group.",
"Fluticasone propionate 750 micrograms/day versus beclomethasone dipropionate 1500 micrograms/day: comparison of efficacy and adrenal function in paediatric asthma.",
"Improved safety with equivalent asthma control in adults with chronic severe asthma on high-dose fluticasone propionate.",
"Air trapping in mild and moderate asthma: effect of inhaled corticosteroids.",
"Endocrine and lung function in asthmatic children on inhaled corticosteroids.",
"Comparison between sodium cromoglycate (MDI: metered-dose inhaler) and beclomethasone dipropionate (MDI) in treatment of adult patients with mild to moderate bronchial asthma. A double-blind, double-dummy randomized, parallel-group study.",
"Inhaled beclomethasone improves the course of asthma and COPD.",
"Treatment of exercise-induced asthma with beclomethasone dipropionate in children with asthma.",
"Comparison of dose-response effects of inhaled beclomethasone dipropionate and budesonide in the management of asthma.",
"Efficacy of inhaled steroids (beclomethasone dipropionate) for treatment of mild to moderately severe asthma in the emergency department: a randomized clinical trial.",
"Significant variability in response to inhaled corticosteroids for persistent asthma.",
"Formoterol and beclomethasone versus higher dose beclomethasone as maintenance therapy in adult asthma.",
"Growth of prepubertal children with mild asthma treated with inhaled beclomethasone dipropionate.",
"Comparative clinical study of inhaled beclomethasone dipropionate and triamcinolone acetonide in persistent asthma.",
"Dose-related effect of beclomethasone dipropionate on airway responsiveness in asthma.",
"High doses of inhaled corticosteroids in unstable chronic asthma. A multicenter, double-blind, placebo-controlled study.",
"Equivalence of salbutamol 200 microg four times daily propelled by propellants 11 and 12 or HFA 134a in mild to moderate asthmatics. Eastern European study group.",
"Effect of inhaled beclomethasone dipropionate on bronchial responsiveness in patients with asthma.",
"A randomized, double-blind comparison of beclomethasone dipropionate extrafine aerosol and fluticasone propionate.",
"Effects of high dose inhaled beclomethasone dipropionate, 750 micrograms and 1500 micrograms twice daily, and 40 mg per day oral prednisolone on lung function, symptoms, and bronchial hyperresponsiveness in patients with non-asthmatic chronic airflow obstruction.",
"Evaluation of different inhaled combination therapies (EDICT): a randomised, double-blind comparison of Seretide (50/250 microg bd Diskus vs. formoterol (12 microg bd) and budesonide (800 microg bd) given concurrently (both via Turbuhaler) in patients with moderate-to-severe asthma.",
"Efficacy and safety of fluticasone propionate/salmeterol HFA 134A MDI in patients with mild-to-moderate persistent asthma.",
"Airway and systemic effects of hydrofluoroalkane fluticasone and beclomethasone in patients with asthma.",
"Equivalence of as-required salbutamol propelled by propellants 11 and 12 or HFA 134a in mild to moderate asthmatics. German Study Group.",
"Proventil HFA provides protection from exercise-induced bronchoconstriction comparable to proventil and ventolin.",
"Fluticasone propionate 1 mg daily and beclomethasone dipropionate 2 mg daily: a comparison over 1 yr.",
"Comparison of addition of salmeterol to inhaled steroids with doubling of the dose of inhaled steroids.",
"Addition of salmeterol versus doubling the dose of beclomethasone in children with asthma. The Dutch Asthma Study Group.",
"Efficacy and safety of fluticasone propionate 44 microg/salmeterol 21 microg administered in a hydrofluoroalkane metered-dose inhaler as an initial asthma maintenance treatment.",
"Aerosol beclomethasone dipropionate compared with theophylline as primary treatment of chronic, mild to moderately severe asthma in children.",
"Clinical efficacy of budesonide Turbuhaler compared with that of beclomethasone dipropionate pMDI with volumatic spacer. A 2-year randomized study in 102 asthma patients.",
"A comparative study of the effects of ketotifen, disodium cromoglycate, and beclomethasone dipropionate on bronchial mucosa and asthma symptoms in patients with atopic asthma.",
"Cumulative dose-response study of non-CFC propellant HFA 134a salbutamol sulfate metered-dose inhaler in patients with asthma.",
"High-dose beclomethasone: oral steroid-sparing effect in severe asthmatic patients.",
"A comparison of inhaled budesonide and beclomethasone dipropionate in childhood asthma.",
"Combined salmeterol/fluticasone propionate versus fluticasone propionate alone in mild asthma : a placebo-controlled comparison."
] |
[
"The improved lung deposition of hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP) extrafine aerosol compared with chlorofluorocarbon beclomethasone dipropionate (CFC-BDP) suggests that lower doses of HFA-BDP may be required to provide equivalent asthma control. The present study was undertaken to test this hypothesis.\n A 10- to 12-day run-in period confirmed that patients met established criteria of at least moderate asthma and the asthma was inadequately controlled by current therapy (inhaled beta-agonist and CFC-BDP [< or = 400 microg/d]). A short course of oral prednisone, 30 mg/d for 7 to 12 days, was followed to establish the patients were steroid responsive and to provide an \"in-study\" baseline of \"optimal\" asthma control.\n A total of 347 patients were then randomized to HFA-BDP 400 microg/d, CFC-BDP 800 microg/d, or HFA-placebo for 12 weeks.\n Morning peak expiratory flow (AM PEF) measurements showed that HFA-BDP 400 microg/d achieved equivalent control of asthma to CFC-BDP 800 microg/d at all time intervals after oral steroid treatment. All other efficacy variables supported the AM PEF results and both active treatments were more effective than placebo. The safety profile of HFA-BDP compared favorably with that of CFC-BDP with no unexpected adverse events reported.\n These findings demonstrate that HFA-BDP provides equivalent control of moderate or moderately severe asthma as CFC-BDP in the population studied, but at half the total daily dose.",
"Beclomethasone dipropionate (BDP) has been reformulated in a chlorofluorocarbon-free propellant, hydrofluoroalkane-134a (HFA), resulting in an extrafine aerosol which gives improved drug delivery to the airways. The objective of this 6 week, placebo-controlled study was to evaluate the clinical efficacy of HFA-BDP 400 micrograms day-1 in 256 adult patients with moderate asthma. This is a lower daily dose than that recommended for existing BDP inhalers in current treatment guidelines for moderate asthma (NIH publication 95-3659). Another objective was to evaluate whether delivering the 400 micrograms dose as four actuations of 50 micrograms twice daily (HFA-BDP 50 micrograms) provided equivalent asthma control to delivering the dose as two actuations of 100 micrograms twice daily (HFA-BDP 100 micrograms) without the use of a spacer or holding chamber. Both active treatments produced a significant change from baseline in morning peak expiratory flow (PEF), which was significantly larger than that in the placebo group (P < or = 0.017) throughout the study. The mean changes from baseline in morning PEF at weeks 5-6 were 47.0 l min-1 in the combined HFA-BDP group and 16.5 l min-1 in the HFA-placebo group. The two dose strengths were statistically equivalent (P = 0.017 for equivalence testing). The active treatments also produced significant improvements compared with placebo in evening PEF, forced expiratory volume in the first second, forced expiratory flow over 25-75% of vital capacity, sleep disturbance scores and daily beta-agonist use. The study medication was well tolerated, with a low incidence of adverse events. The results from this study demonstrate that a daily dose of 400 micrograms HFA-BDP (given in 50 micrograms and 100 micrograms strengths) provides dose proportionality and effective control in patients with moderate asthma.",
"The objective of this study was to evaluate the efficacy and safety of low doses (50 and 100 microg b.i.d.) of hydrofluoroalkane-134a (HFA) beclomethasone dipropionate (BDP) extrafine aerosol in improving asthma control. Reformulation of BDP in a new chlorofluorocarbon (CFC)-free propellant (HFA) has produced an extrafine aerosol with increased delivery of the drug to the airways of the lung. The study population comprised 270 steroid-naive patients with mild to moderate asthma (mean baseline forced expiratory volume in 1 sec [FEV1] as a percentage of predicted normal of 65%-85%). This was a 6-week, blinded, placebo-controlled, multicenter study. Patients were randomized to receive 50 or 100 microg b.i.d. HFA-BDP or HFA-placebo. Treatment with either 50 or 100 microg b.i.d. HFA-BDP resulted in a significantly greater improvement compared with placebo in FEV1 (mean change from baseline as percentage of predicted normal of 6.7%, 8.6%, and 0.4%, respectively; p < or = 0.01 active treatment groups vs. placebo), with a significant trend toward increasing improvement with increasing doses (p < or = 0.0001). Treatment also resulted in significantly greater mean changes from baseline in morning peak expiratory flow compared with placebo (29.5, 33.8, and 5.0 L/min, respectively; p < or = 0.01 active treatment groups vs. placebo). All other pulmonary function and asthma symptom measures supported these data. The study treatments were well tolerated. These results show that low doses of HFA-BDP extrafine aerosol effectively improve asthma control in adult patients with mild to moderate asthma. However, it is important that inhaled corticosteroid therapy is still given at a dose high enough to control airway inflammation as well as asthma symptoms.",
"Beclomethasone dipropionate (BDP) has been formulated as an extrafine aerosol (hydrofluoroalkane-134a [HFA]-BDP) [QVAR; 3M Pharmaceuticals; St Paul, MN], which gives improved lung deposition compared with chlorofluorocarbon (CFC)-BDP. The clinical efficacy of HFA-BDP has been established in adult asthma at a required dose below that of CFC-BDP, but has not been evaluated in children.\n To examine the efficacy and safety of HFA-BDP in childhood asthma.\n A 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study involving 353 children aged 5 to 12 years with moderate, symptomatic asthma. After a 2-week run-in period, patients were randomized to HFA-BDP, 80 micro g/d (n = 120); HFA-BDP, 160 micro g/d (n = 117); or HFA-placebo (n = 116) administered twice daily.\n Hospital outpatient.\n HFA-BDP, 80 micro g/d and 160 micro g/d, produced a significant, dose-related increase from baseline in FEV(1) percent predicted compared with placebo. At week 12, mean changes from baseline in FEV(1) percent predicted were 9.2% (p < or = 0.01 vs placebo), 10% (p < or = 0.01 vs placebo), and 3.9% for the HFA-BDP 80 micro g/d, HFA-BDP 160 micro g/d, and placebo groups, respectively. There was also a significant decrease in daily beta-agonist use, improvement in peak expiratory flow, and increase [correction] in the percentage of days free from asthma symptoms (p < or = 0.05 for HFA-BDP, 160 micro g/d, vs placebo at weeks 11 to 12). HFA-BDP was well tolerated, with no significant differences in the incidence or nature of adverse events between HFA-BDP and placebo groups. Neither were there significant differences between groups in mean percentage change from baseline in the morning plasma cortisol level at week 12 or in the percentage of patients with morning plasma cortisol levels below the reference range at baseline and week 12. In a subgroup tested, the percentage of patients with an abnormal response to low-dose adrenocorticotropic hormone stimulation at week 12 was low and similar among all groups.\n HFA-BDP, 80 to 160 micro g/d, is effective and safe in childhood asthma.",
"Inhaled corticosteroids are recognized as first-line therapy in the management of asthma; however, their use may be limited by systemic and local side-effects. Ciclesonide, a novel pro-drug inhaled corticosteroid, is activated in the lungs and is expected to have less systemic and local side-effects. This study evaluated the efficacy and safety of ciclesonide in hydrofluoroalkane (HFA) compared with beclomethasone dipropionate (BDP) in a chlorofluorocarbon (CFC) formulation in adult patients with moderate to severe asthma.\n This was a multicentre, randomized, open-label, parallel-group comparative study. The patients were given 800 microg/day of CFC-BDP in the four-week baseline period. After the baseline period, 319 patients were randomly allocated into three groups which, respectively, received HFA-ciclesonide 400 microg/day (without a spacer), HFA-ciclesonide 800 microg/day (without spacer) and CFC-BDP 800 microg/day (with spacer) for the eight-week treatment period. The primary efficacy variable was morning PEF.\n The morning PEF increased by 16.02 L/min in the 400 microg HFA-ciclesonide group, 23.98 L/min in the 800 microg HFA-ciclesonide group and 5.91 L/min in the 800 microg CFC-BDP group. Better outcomes were achieved by the use of 800 microg/day of HFA-ciclesonide compared with 800 microg/day of CFC-BDP (P = 0.001). There was no difference in adverse events between the groups.\n In adult patients with moderate to severe asthma, 800 microg/day of HFA-ciclesonide was significantly more effective than 800 microg/day of CFC-BDP. Ciclesonide at doses of 400 microg/day and 800 microg/day was safe and well tolerated.",
"Inflammation in asthma extends into the small airways (< 2 mm diameter). Most inhaled corticosteroids are suspensions with a particle size > 2 mm. Therefore, inflammation in the small airways of patients with asthma may not be adequately treated with these preparations. Some inhaled corticosteroids, on the other hand, are compounded with alcohol, resulting in a solution producing an aerosol that has a mean particle diameter of < 2 mm. This study was designed to compare the addition of equivalent amounts of two inhaled corticosteroids (one a suspension and one a solution) to the treatment of patients with asthma, which was uncontrolled despite treatment with moderate to high doses of inhaled corticosteroids and usually additional controller medications. The study was performed with 30 patients, > or = 18 years of age. Subjects were randomized in a single-blind fashion to receive, in addition to their current asthma therapy, either CFC-FP 220 microg each morning and 110 microg each evening (n = 10) or HFA-BDP 160 mcg twice daily (n = 20). Pre- and postbronchodilator spirometry, single breath nitrogen washout for closing volume and residual volume by plethysmography were assessed before and after 3 months of therapy. In the subjects who received HFA-BDP, the ratio of closing volume (CV) to vital capacity (VC) and residual volume (RV) decreased significantly (p = 0.0214 and 0.0433, respectively), whereas forced expiratory flow over 25-75% of the vital capacity (FEF25-75%), forced expiratory volume in 1 second (FEV1), and morning peak flow improved significantly (p = 0.0014, 0.0184, and 0.0321). Improvements from baseline of CV, CV/VC, and postbronchodilator FEF25-75%, were statistically significant in the HFA-BDP group compared with the CFC-FP group (p = 0.0049, 0.0194, and 0.0355, respectively). These preliminary findings suggest that the addition of HFA-BDP, compared with CFC-FP in patients with poorly controlled asthma despite receiving moderate to high doses of inhaled steroids, has a greater effect on parameters reflecting small airway patency presumably secondary to reduction in inflammation.",
"Hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP) extra-fine aerosol and HFA-fluticasone propionate (HFA-FP) are chlorofluorocarbon-free inhalers. We conducted an 8-week, open study to demonstrate the equivalence of HFA-BDP (800 microg day(-1)) and HFA-FP (1000 microg day(-1)) in moderate to severe asthma. Symptomatic patients on 500-1000 microg day(-1) CFC-BDP (or equivalent) and short-acting beta-agonist, were randomized to HFA-BDP (n = 101) or HFA-FP (n = 97) after 7-14 (+/-2) day run-in. In the intent-to-treat (ITT) population (n = 198), both treatments provided clinically and statistically significant improvements in asthma control, with increases in peak expiratory flow in the morning (AM PEF) and asthma symptoms (within treatment analysis P<0.05). Mean (SE) change in AM PEF from baseline at week 8 was equivalent (defined as 90% CI for the mean difference between treatments within +/-25 l min(-1)) in the two groups: 29.59 (5.19) l min(-1) for HFA-BDP vs. 17.3 (5.45) l min(-1) for HFA-FP (90% CI-0.02, 24.91). For the perprotocol population (n = 121), the mean (SE) change in AM PEF from baseline was not equivalent; AM PEF improved to a significantly greater extent in the HFA-BDP group than HFA-FP group [34.84 (7.08) vs. 20.63 (7.32) l min(-1) P<0.01; 90% CI; 2.66, 31.10]. At week 8 in the ITT population, there were no statistically significant differences in FEV1, beta-agonist use, asthma symptom/sleep disturbance scores, or percentage of days without asthma symptoms/sleep disturbance. There was a significantly greater reduction from baseline in mean eosinophil count for HFA-BDP compared with HFA-FP at weeks 3 and 8 (P<0.01), and eosinophil cationic protein value at week 8 (P<0.01). Both treatments were well tolerated and there were no statistically significant differences in urinary cortisol creatinine parameters. In conclusion, this study showed that, in patients with moderate-to-severe symptomatic asthma, HFA-BDP extra-fine aerosol 800 microg(-1) was at least as effective and equally well tolerated as 1000 microg day(-1) HFA-FP.",
"Beclometasone dipropionate (BDP) extrafine is a hydrofluoroalkane-based, chlorofluorocarbon (CFC)-free inhalation aerosol. This study was conducted to determine whether BDP extrafine and CFC-fluticasone proprionate (FP) aerosols were equivalent in terms of efficacy and tolerability in children with symptomatic mild-to-moderate asthma. Male and female patients (aged 5-12 yr) with an asthma diagnosis for > or =3 months, peak expiratory flow (PEF) > or =60% of predicted normal and suboptimal asthma control were randomised to double-blind treatment with BDP extrafine 200 microg day(-1) (n=139) or CFC-FP 200 microg day(-1) (n=141) for up to 18 weeks. After 6 and 12 weeks, study medication was 'stepped down' to 100 and 50 microg day(-1), respectively, if patients had achieved good asthma control. Patients with poor asthma control discontinued from the study and those with intermediate control continued in the study but did not undergo a dose reduction. The estimated treatment difference in morning PEF% predicted at 6 weeks was -1.9% (90% CI -4.9, 1.0). There was a trend towards a greater increase in forced vital capacity (% predicted) in the BDP extrafine group (5.3 versus 0.4%; p=0.084). A 'step-down' in therapy to 100 microg day(-1) was possible in 36% and 42% of patients in the BDP extrafine and CFC-FP groups, respectively, at 6 weeks. Both drugs were well tolerated. BDP extrafine and CFC-FP aerosols were equally effective at improving asthma control in children with mild-to-moderate asthma at the same daily dose.",
"Options for step-down therapy include use of inhaled corticosteroids alone or in combination with a long-acting beta2-agonist.\n We sought to evaluate step-down therapy with a fluticasone propionate-salmeterol (FP-SM) combination administered through a dry powder inhaler (DPI; Advair Diskus) versus a medium dose of hydrofluoroalkane 143a-beclomethasone dipropionate (HFA-BDP) administered through a breath-actuated pressurized metered-dose inhaler (QVAR Autohaler).\n Thirty-nine patients with uncontrolled moderate-to-severe asthma were treated with 1000 microg of DPI-administered BDP twice daily (DPI-BDP) for 4 weeks and then randomized to 200 microg of HFA-BDP twice daily (n = 20) or 100 microg of FP and 50 microg of SM twice daily (FM-SM; n = 19) for 8 weeks in a double-blind, double-dummy, parallel-group design. We measured the provocative dose of methacholine producing a 20% fall in FEV1 (methacholine PD20) as the primary outcome, with secondary outcomes being lung function, surrogate inflammatory markers, diary card responses, quality of life, and safety.\n There was a 0.9 (95% confidence interval, 0.5-1.2) doubling dose improvement in methacholine PD20 comparing asthma before versus after DPI-BDP. HFA-BDP maintained this improvement, whereas FP-SM produced a further significant improvement, amounting to a 1.1 (95% confidence interval, 0.2-2.1) doubling dose difference at 8 weeks for FP-SM versus HFA-BDP. Effects on FEV1, peak expiratory flow, and quality of life (symptoms and emotions) were similar to those on methacholine PD20, with a significant difference between FP-SM and HFA-BDP. Suppression of plasma and urinary cortisol and serum osteocalcin levels occurred with DPI-BDP, but values returned to baseline levels within 1 month of HFA-BDP or FP-SM administration.\n After high-dose inhaled corticosteroid, stepping down with the combination inhaler conferred further improvements in bronchoprotection, bronchodilatation, and clinical control, but not inflammatory markers, compared with that seen with a medium dose of inhaled corticosteroid.",
"To compare the efficacy and safety of a double-strength formulation of beclomethasone dipropionate (BDP 84) metered-dose inhaler (MDI) with that of beclomethasone dipropionate (BDP 42) MDI in the treatment of chronic asthma.\n A 28-day, randomized, double-blind, double-dummy, placebo-controlled, multicenter study.\n Outpatient.\n A total of 423 patients aged 12 to 65 years (mean range, 34 to 36 years) with moderate asthma (FEV1, 50 to 80% of predicted) who required long-term inhaled corticosteroids were enrolled.\n Patients were randomized to receive BDP 84, two oral inhalations bid (336 microg/d), BDP 42, four oral inhalations bid (336 microg/d), or placebo. A fourth treatment arm administering BDP 84, eight oral inhalations bid (HD BDP 84; 1,344 microg/d) was also included to determine whether a dose-response relationship could be demonstrated.\n Spirometry, clinical observations.\n The three active treatments were significantly more effective (p < or = 0.01) than placebo at all time points in improving FEV1, the primary efficacy parameter; BDP 42 and BDP 84 were comparable to each other at every time point. Secondary pulmonary function tests (FVC, forced expiratory flow at 25 to 75% of FVC, and peak expiratory flow rate) showed similar results. All three active treatments were well tolerated. A dose response between 336 microg/d and 1,344 microg/d was demonstrated.\n In this well-controlled 28-day study, BDP 42 and BDP 84 were shown to be comparable in efficacy and safety on a microgram-for-microgram basis.",
"There are still some concerns about the safety of high doses of inhaled glucocorticosteroids (ICS). We compared the safety and efficacy of fluticasone propionate (FP) and beclomethasone dipropionate (BDP) in 306 patients with moderate to severe asthma in a double-blind, multicenter, cross-over study of 12 mo duration. During the 1-mo run-in period, bronchodilators were replaced by salmeterol 50 microg twice daily, increasing morning peak expiratory flow rate (PEFR) by 28 L/min (p < 0.001) and FEV1 by 6.2% predicted (p < 0.001). At randomization the current ICS was replaced by 500 microg BDP or 250 microg FP in accordance with previously taken 500 microg BDP or 400 microg budesonide (BUD). No significant differences between the two treatments regarding morning plasma cortisol, urinary excretion of calcium and hydroxyproline, FEV1, and PEFR were observed at any time point during the study. Osteocalcin and bone mineral density (BMD) were improved over baseline in the FP group, resulting in higher serum osteocalcin levels (mean difference 0.28 ng/ml; p < 0.001) and higher BMD in the spine (1.0%; p = 0.05), femoral neck (1.6; p < 0.01), and Ward's triangle (3.6%; p = 0.01) as compared with BDP. We conclude that chronic treatment with FP, at half the dose of BDP, results in a similar antiasthma effect but a more favorable safety profile with respect to bone metabolism and mineral density.",
"A six-month double-blind controlled trial compared a 2,000 microgram per day dose of beclomethasone dipropionate aerosol (BDP), with current upper level doses of 800 micrograms per day of the standard BDP, in asthmatics requiring oral corticosteroids in addition to BDP and bronchodilators. Both groups showed a significant reduction in their oral steroid requirements during the study, with a 34 percent reduction in the lower dose group and a 57 percent reduction in the high dose BDP group while maintaining good symptomatic control of asthma; there was an associated improvement in baseline serum cortisol levels. Over the same period, the pulmonary function of the lower dose group showed significant worsening relative to that of the group receiving the high dose BDP which improved. There was no increase in dysphonia or oropharyngeal candidiasis among those using the concentrated BDP. We conclude that high dose concentrated BDP appears to be a safe medication in long-term steroid-dependent asthma, and is effective in reducing dependence on the use of oral corticosteroid with associated improvement both in pulmonary and adrenal function.",
"To evaluate the clinical efficacy of high dose inhaled steroids, we examined the effects of standard doses (400 micrograms/day) and high doses (800 micrograms/day) of inhaled beclomethasone dipropionate (BDP, Becotide Inhaler), and the dose for regular use (800 micrograms/day) of salbutamol (Salb. Asmidon Air) on pulmonary function, bronchial hyperresponsiveness and asthma attack score. The subjects were 17 out-patients with mild or moderate bronchial asthma who were not receiving any anti-allergics or steroids. The patients were randomly allocated into three groups i.e., Group I: BDP 400 micrograms/day, Group II: BDP 800 micrograms/day and Group III: Salb. 800 micrograms/day. The administration period was 8 weeks. Pulmonary function test were performed and bronchial hyperresponsiveness was examined before and after the 8 weeks of treatment and attack scores were recorded during this period. It was found that inhalations of 400 micrograms/day and 800 micrograms/day BDP improved FEV1.0% value, peak flow, F-V curve, Dmin. and SGrs/Grs cont. Particularly, inhalation of 800 micrograms/day of BDP significantly improved these values and reduced attack scores in the early stages of the 8 week treatment. In contrast, there was a trend for inhalation of Salbutamol to enhance bronchial hyperresponsiveness and not to improve pulmonary function and asthma attack score. In conclusion, 800 micrograms/day of inhaled BDP is considered to be useful in the treatment of mild or moderate bronchial asthma.",
"We wanted to evaluate the improvement in efficacy when increasing the daily dose of inhaled steroids and to compare the efficacy, safety, and tolerance of 1.6 mg beclomethasone dipropionate (BDP) with that of 2.0 mg fluticasone propionate (FP). The study was a randomized, double-blind, 3 month, multicentre study. One hundred and thirty four asthmatics currently using inhaled steroids (0.4-1.6 mg BDP or budesonide (BUD)) were stratified according to pretrial daily steroid use. Within each stratum they were randomized to either 1.6 mg BDP or 2.0 mg FP. A significant increase in the primary efficacy variables, i.e. mean morning and evening peak expiratory flow (PEF) (approximately 20 l.min-1) during the treatment period, was found for both treatments. No significant differences between the drugs were revealed for these primary or any other secondary efficacy variables (use of beta 2-agonists, symptom scores, and PEF, forced vital capacity (FVC), forced expiratory volume in one second (FEV1) recorded at the clinical visits). However, significant differences between treatments occurred regarding decrease of serum cortisol and adrenocorticotropic hormone. We conclude that, although both treatments gave statistically significant increases in efficacy parameters when compared with baseline, the increases were so small that they can be regarded as being clinically unimportant. Daily doses of BDP, 1.6 mg, and FP, 2.0 mg, had comparable effects on lung function. A suppression of the hypothalamic pituitary adrenal (HPA) axis was only found with a daily dose of 2 mg FP.",
"Sixteen patients suffering from bronchial asthma, with or without chronic bronchitis, sufficiently severe to be treated with inhaled corticosteroids, were studied in a single-blind trial (blind observer) of beclomethasone dipropionate (BDP) given in three randomized dosage regimens: 500, 1000 and 2000 micrograms per day, each for 4 weeks. The beta 2-adrenergic agonist response curve showed a dose-dependent increase in FEV1 which was not affected by different doses of BDP. A small but significant reduction in basal cortisol levels was observed after BDP 500 micrograms/day. There was no significant difference between the various doses of BDP in reducing cortisol level and stimulation with tetracosactide remained unchanged. The study showed a gradual, dose-dependent improvement in lung function, statistically significant for morning peak expiratory flow rate at BDP 2000 micrograms/day. Dyspnoea score and beta 2-agonist use decreased, reflecting the anti-asthmatic effects. An increase in total leukocyte count was observed, together with a decrease in the eosinophil count. Oral candidiasis was seen in 2 out of 16 patients. It is concluded that the clinical anti-asthmatic effects of corticosteroid treatment by inhalation are not due to modulation of beta 2-receptor function in the airways.",
"Guidelines on asthma management recommend that in patients who still have symptoms on treatment with low-dose inhaled corticosteroids the first step should be an increase in inhaled corticosteroid dose. The addition of long-acting inhaled beta 2-adrenoceptor agonists is another option. We have compared these two strategies in a randomised, double-blind, parallel-group trial. We studied 429 adult asthmatic patients who still had symptoms despite maintenance treatment with 200 micrograms twice daily inhaled beclomethasone dipropionate (BDP). 3 did not provide verifiable data. Of the others, 220 were assigned salmeterol xinafoate (50 micrograms twice daily) plus BDP and 206 were assigned higher-dose BDP (500 micrograms twice daily) for 6 months. The mean morning peak expiratory flow increased from baseline in both groups, but the increase was greater in the salmeterol/BDP group than in the higher-dose BDP group at all time points (differences 16-21 L/min, p < 0.05). Mean evening PEF also increased with salmeterol/BDP but not with higher-dose BDP. There were significant differences in favour of salmeterol/BDP in diurnal variation of PEF (all time points) and in use of rescue bronchodilator (salbutamol) and daytime and night-time symptoms (some time points). There was no significant difference between the groups in adverse effects or exacerbations of asthma, indicating that in this group of patients regular beta 2-agonist therapy was not associated with any risk of deteriorating asthma control over 6 months. This study suggests a need for a flexible approach to asthma management.",
"Previous studies have suggested a 2:1 efficacy advantage of fluticasone propionate (FP) over beclomethasone dipropionate (BDP) in adults on high dose inhaled steroids and children on low dose inhaled steroids. The lower doses of FP required to provide equivalent efficacy to BDP also appear to have fewer systemic effects as measured by adrenal function.\n The efficacy and safety of FP 750 micrograms/day and BDP 1500 micrograms/day were compared in 30 children with persistent asthma (requiring 1000-2000 micrograms/day of inhaled corticosteroids) in a 12 week randomised double blind crossover study. Medication was delivered by a spacer device in two divided doses. Primary efficacy variables were peak expiratory flows (PEF). Adrenal function was assessed by 24 hour urinary free cortisol levels at eight and 12 weeks and ACTH and low dose synacthen tests (LDST) at 12 weeks. The results were adjusted for sequence and period differences.\n There was no difference in the primary efficacy variables over the two 12 week treatment periods (difference in adjusted means for morning PEF 1.3 l/min (95% CI -6.1 to 8.8), p = 0.112) and symptom scores (cough, tachypnoea, wheeze, shortness of breath; difference in adjusted means of night time scores: -0.06 (95% CI -0.14 to 0.03); p = 0.136). Similar degrees of mild adrenal dysfunction were found during BDP and FP treatment phases. Identical height gain velocities were shown during the corresponding periods.\n FP 750 micrograms/day is as effective as BDP 1500 micrograms/day in children with persistent asthma. At these very high doses we were unable to demonstrate a safety advantage of FP over BDP as assessed by adrenal function. However, measures of adrenal function may have been influenced by concurrent and previous systemic steroid usage, and possibly by effects of disease activity.",
"High-dose inhaled corticosteroids (ICS) have been associated with the same side-effects as oral corticosteroids. Beclomethasone dipropionate (BDP) and budesonide (BUD) in doses greater than 2000 microg/day are used regularly in severe asthma, despite the fact that safety and efficacy data at such high doses are limited. Fluticasone propionate (FP) has been promoted as being twice as potent clinically as BDP or BUD at doses of 2000 microg/day or less with a similar safety profile. The aim of this study was to compare the efficacy and safety of FP with BDP and BUD in 133 symptomatic adult asthmatics requiring at least 1750 microg/day of BDP or BUD.\n Patients fulfilling the entry criteria were randomized to receive either their regular ICS medication or FP at approximately half the microgram dose for 6 months in an open, parallel group study. The primary efficacy measure was based on morning peak expiratory flow measurements recorded by patients on daily record cards, while determination of safety was based on a number of endpoints including changes in bone turnover indices, the incidence of topical side-effects and assessments of quality of life.\n It was shown that patients who were switched to FP, but not those continuing with BDP or BUD, had significant increases in levels of morning serum cortisol and the urine cortisol:creatinine ratio while maintaining asthma control. Serum osteocalcin and the pyridinoline:creatinine ratio, as well as the deoxypyridinoline:creatinine ratio, were also shown to increase only in the FP group. Subjective assessments such as quality of life score, the incidence and ease of bruising, and reports of hoarseness also favoured the FP group.\n It is concluded that, at the doses studied and with the delivery devices used clinically, FP is at least as effective as BDP/BUD in the management of severe asthma and may offer clinical advantages with respect to steroid-related adverse effects.",
"Air trapping reflects small airway obstruction in asthma and can be assessed quantitatively by high-resolution computed tomography (HRCT). Hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP) is deposited across all sizes of airways, including the small ones. However, its long-term effect on air trapping remains unknown in uncontrolled asthma.\n To compare the effect of inhaled corticosteroids of different particle size - HFA-BDP and fluticasone propionate (FP) - on lung attenuation in mild-to-moderate uncontrolled asthma.\n A randomized study was performed to analyze the effect of HFA-BDP (400 microg/d) or FP (500 microg/d) given over a period of 3 months to patients with uncontrolled mild-to-moderate asthma. HRCT was performed with spirometric gating, and lung attenuation was measured at residual volume and at pulmonary total capacity. The difference between inspiratory and expiratory attenuation was calculated as an air trapping index.\n Twenty-five out of 58 patients had abnormal air trapping and could be included in the study. Lung attenuation significantly diminished in the posterior zones of the lung after a 3-month treatment with HFA-BDP or FP, but the difference between the groups was not significant. Adjusted mean variations of the air trapping index from baseline to treatment completion were 34.3 (11.2, 57.3) and 27.3 (6.4, 48.2) for the HFA-BDP and FP groups, respectively. However, the reduction of air trapping area was more pronounced in the group treated with HFA-BDP.\n Inhaled corticosteroids decrease air trapping in uncontrolled asthma regardless of their particle size.\n In mild-to-moderate asthma, air trapping assessed by HRCT may be a new outcome related to the control of the disease.",
"The safety of inhaled corticosteroids in the treatment of chronic asthma has been questioned. In a prospective crossover study asthmatic children not controlled on other medications were commenced on beclomethasone dipropionate (BDP) or budesonide (BUD), both administered at the dose of 200 micrograms twice per day for 2 wk each in randomized order. Recordings at home included twice daily symptom scores, peak expiratory flow readings, and the use of additional antiasthma medications. Before and after each treatment period the patients were admitted for overnight blood sampling for cortisol, ACTH, and growth hormone, 24-h urine collections for cortisol, and detailed lung function tests. A total of 12 children completed the study. The nocturnal serum cortisol production was significantly reduced by 27 and 35% after 2 and 4 wk of treatment (p = 0.005, p = 0.004; Wilcoxon test), and the urinary free cortisol showed a similar reduction of 33 and 48% (p = 0.023, p = 0.005). Such suppression could be shown on both drugs, BDP and BUD, and there was no significant difference between them. The ACTH and growth hormone values were not significantly changed on any treatment. Lung function tests showed an impressive improvement in FVC, FEV1, FEF50, and FEF25 after 2 wk of treatment regardless of the medication. Differences in lung function improvements between the two drugs were very small and not of clinical relevance. The observations indicate that even low-dose inhaled corticosteroids in the form of BDP or BUD have a systemic effect, which emphasizes the importance of using the minimum dose compatible with good control of asthma.",
"This study compared the efficacy and tolerability of sodium cromoglycate (SC) and beclomethasone dipropionate (BDP) in adult patients with bronchial asthma inadequately treated with bronchodilators alone. The study was a double-blind, randomized, double-dummy, parallel-group study. Patients with mild to moderate symptomatic asthma, inadequately treated with bronchodilators only, were, after a 2-week run-in (base-line) period, randomized to 8 weeks of treatment with either SC 10 mg four times daily or BDP 100 micrograms four times daily. Salbutamol metered-dose inhaler was given as relief medication. A total of 37 patients were randomized for treatment, 19 patients in the SC group and 18 patients in the BD group. Efficacy and safety were determined by daily record card data: morning and evening peak-expiratory-flow rates (PEFR), daytime and nighttime asthma symptom scores, and rescue salbutamol use. At clinic visits, FEV1 and FVC were measured, as were the physician's and the patient's assessment of the medication at the end of the study. The safety and tolerability of the trial medication were assessed by monitoring adverse events throughout the study. A clinically and statistically significant improvement of the asthma in FEV1, symptom scores, rescue medication, and global opinion of efficacy was observed, and both groups provided equivalent efficacy. The morning PEFR as well as the evening PEFR for both groups improved, but was statistically significant only for the BDP group (M-PEFR). Both drugs were well tolerated with only a few minor adverse events. This trial shows that SC and BDP are equally effective anti-inflammatory treatments for mild to moderate bronchial asthma in adults.",
"The effects of inhaled beclomethasone dipropionate (BDP), 800 micrograms daily, on the long-term course of asthma and chronic obstructive pulmonary disease (COPD) were investigated in a prospective, controlled study, over three years. During the first two years, patients were treated with a bronchodilator only (salbutamol or ipratropium bromide). Fifty six patients (28 asthma, 28 COPD), with an unfavourable course of disease during bronchodilator therapy alone (an annual decline in forced expiratory volume in one second (FEV1) of > or = 80 ml.yr-1 in combination with at least one exacerbation.yr-1), were selected for additional treatment with inhaled beclomethasone dipropionate (BDP), 800 micrograms daily, during the third year. The FEV1 and provoking concentration of histamine producing a 20% fall in FEV1 (PC20-histamine) were assessed at six-monthly intervals. In asthma, the annual decline in prebronchodilator FEV1 of -158 ml.yr-1 during bronchodilator therapy alone was followed by a significant increase of 562 ml.yr-1 during months 1-6 of BDP treatment (p < 0.0005). During months 7-12 of BDP, the FEV1 declined slightly with -31 ml.yr-1, which was not statistically different from the annual decline before steroid therapy (p = 0.17). In COPD, the increase of 323 ml.yr-1 during months 1-6 of treatment with BDP was different from the annual decline of -156 ml.yr-1 before BDP (p < 0.05). The PC20-histamine improved by 308 doubling doses during 1-12 months of BDP in asthma (p < 0.05) but not in COPD.(ABSTRACT TRUNCATED AT 250 WORDS)",
"A new hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP) aerosol markedly increases drug delivery to the airways. Therefore, even low doses of HFA-BDP should be effective, and the present study assesses this. A randomised, double-blind, crossover study was used to compare the effect of placebo, HFA-BDP 50 microg or 100 microg given q.d. (QVAR(TM) Autohaler(TM); 3M Pharmaceuticals, St. Paul, MN, USA) on exercise-induced bronchoconstriction and exhaled nitric oxide (eNO). After a 14-day run-in, 25 children (5-14 yrs old) entered three 4-week treatment periods, separated by a 1-week washout. After each period, the fall in forced expiratory volume in one second (FEV1), after an exercise test, and eNO were measured. Significant treatment effects with no carry-over or period effects were seen for both eNO and maximum fall in FEV1 after exercise. Differences were seen between placebo (fall in FEV1=27.9%; eNO=14.4 parts per billion (ppb)) and either dose of HFA-BDP, but not between the two active doses (50 microg: fall in FEV1=20.8%, eNO=9.3 ppb; 100 microg: fall in FEV1=20.9%, eNO=8.9 ppb). In conclusion, low q.d. doses of hydrofluoroalkane-beclomethasone dipropionate reduced exhaled nitric oxide and exercise-induced bronchoconstriction. Further studies are needed to assess whether q.d. administration of beclomethasone dipropionate is as effective as b.i.d. administration.",
"The dose-response effects of inhaled beclomethasone dipropionate (BDP) and budesonide (BUD) administered b.i.d. with the aid of metered dose aerosols were studied in 128 patients (67 men and 61 women, mean age 53 years) suffering from asthma bronchiale. The study was designed as a multi-centre, double-blind, four-period cross-over study, followed by a single-blind double placebo period. BDP was administered in doses of 400 and 1000 micrograms, and BUD in doses of 400 and 800 micrograms. The results in terms of peak expiratory flow (PEF) in the morning and evening, daily symptoms score and use of inhaled beta 2-agonists did not reveal any clinically significant differences between the drugs or between high (800 micrograms BUD, 1000 micrograms BDP) and low (400 micrograms BUD/BDP) doses. However, statistically significant differences were recorded for the corresponding parameters when comparing the placebo with preceding steroid periods. Adverse effects consisting mainly of oropharyngeal candidiasis, hoarseness and cough occurred in 54 of 468 treatment months (12%). The carry-over effects of inhaled steroids are longer lasting than was previously assumed.",
"To examine the efficacy of an inhaled steroid, when added to a standard regimen of beta-agonist therapy, in the treatment of patients with mild to moderately severe asthma in the emergency department.\n A convenience sample of adult patients with asthma (FEV1 % predicted 40% to 69%) presenting to the ED was randomly assigned in a double-blind fashion into 2 treatment groups. The first group received 2.5 mg nebulized salbutamol plus 1 mg (4 puffs) of beclomethasone dipropionate (BDP) at baseline, 30 minutes, and at 1, 2, and 4 hours, delivered by a metered-dose inhaler (MDI) attached to a spacer device (Vent-AH-aler, Glaxo). The second group was given the same salbutamol regimen plus MDI placebo through the Vent-AH-aler. The primary endpoint was improvement in FEV1 %predicted at 6 hours.\n Of 54 patients enrolled, 28 were assigned to the BDP group and 26 to the placebo group. Spirometry improved significantly in both groups over the 6 hours compared with baseline (ANOVA, P <.001). At 6 hours, the mean absolute improvement in FEV1 % predicted for BDP was 18% versus 17% for placebo (95% confidence interval for the absolute difference of 1% [-8% to 10%]). The proportion of patients in the BDP group who were hospitalized was 7% compared with 19% for patients in the placebo group (95% confidence interval for the difference of 12% [-6%, 30%]).\n In this group of patients with mild to moderately severe asthma, 5 mg BDP delivered by MDI during the initial 4 hours of an emergency visit was of no added benefit over standard therapy, as measured by improvement in FEV1 % predicted at 6 hours. However, a trend toward a difference in admission favoring BDP was observed. [Afilalo M, Guttman A, Colacone A, Dankoff J, Tselios C, Stern E, Wolkove N, Kreisman H: Efficacy of inhaled steroids (beclomethasone dipropionate) for treatment of mild to moderately severe asthma in the emergency department: A randomized clinical trial.",
"A clinical model is needed to compare inhaled corticosteroids (ICSs) with respect to efficacy.\n The purpose of this investigation was to compare the relative beneficial and systemic effects in a dose-response relationship for 2 ICSs.\n A 24-week, parallel, open-label, multicenter trial examined the benefit-risk ratio of 2 ICSs in persistent asthma. Benefit was assessed by improvements in FEV(1) and PC(20); risk was assessed by overnight plasma cortisol suppression. Thirty subjects were randomized to either beclomethasone dipropionate (BDP) 168, 672, and 1344 microg/day (n = 15) or fluticasone propionate (FP) 88, 352, and 704 microg/day (n = 15), both administered by means of a metered dose inhaler (MDI) with chlorofluorocarbon propellant via a spacer, in 3 consecutive 6-week intervals; this was followed by 3 weeks of FP dry powder inhaler (DPI) 2000 microg/day.\n Maximum FEV(1) response occurred with the low dose for FP-MDI and the medium dose for BDP-MDI and was not further increased by treatment with FP-DPI. Near-maximum methacholine PC(20) improvement occurred with the low dose for FP-MDI and the medium dose for BDP-MDI. Both BDP-MDI and FP-MDI caused dose-dependent cortisol suppression. Responsiveness to ICS treatment was found to vary markedly among subjects. Good (>15%) FEV(1) response, in contrast to poor (<5%) response, was found to be associated with high exhaled nitric oxide (median, 17.6 vs 11.1 ppb), high bronchodilator reversibility (25.2% vs 8.8%), and a low FEV(1)/forced vital capacity ratio (0.63 vs 0.73) before treatment. Excellent (>3 doubling dilutions) improvement in PC(20), in contrast to poor (<1 doubling dilution) improvement, was found to be associated with high sputum eosinophil levels (3.4% vs 0.1%) and older age at onset of asthma (age, 20-29 years vs <10 years).\n Near-maximal FEV(1) and PC(20) effects occurred with low-medium dose for both ICSs in the subjects studied. High-dose ICS therapy did not significantly increase the efficacy measures that were evaluated, but it did increase the systemic effect measure, overnight cortisol secretion. Significant intersubject variability in response occurred with both ICSs. It is possible that higher doses of ICSs are necessary to manage more severe patients or to achieve goals of therapy not evaluated in this study, such as prevention of asthma exacerbations.",
"A total of 132 adult asthmatics who were symptomatic on 500 microg x day(-1) inhaled beclomethasone dipropionate (BDP) were studied in an open-label randomized, parallel group, 12 week, clinical trial. The addition of 12 microg formoterol fumarate solution aerosol (pressurized metered dose inhaler) b.i.d. to BDP at a dose of 500 microg x day(-1) was compared with a higher dose of 1,000 microg x day(-1) BDP. Mean morning premedication peak expiratory flow rate (PEF) during the final week of treatment (primary end-point) increased in both groups compared to baseline. The estimated treatment difference of 20.4 L x min(-1) (95% confidence interval 3.2-37.6) after 12 weeks of treatment was statistically significant (p<0.05) in favour of the formoterol/BDP group. The overall mean morning premedication PEF for the entire treatment period was higher in the formotero/BDP group (p=0.002). The overall number of puffs of rescue medication and asthma symptom scores were less in the formotero/BDP group (p<0.01). Safety and tolerability evaluations were satisfactory in both groups. In conclusion, the results suggest that the addition of formoterol fumarate to the existing dose of an inhaled corticosteroid should be considered as an alternative to increasing the dose of inhaled corticosteroid in the inadequately controlled asthmatic.",
"Poorly controlled severe asthma can lead to growth impairment in childhood. In children with mild asthma, it is less clear whether treatment influences growth or adrenal function. We determined in a randomized, double-blind, placebo-controlled, community-based study, the effect of inhaled beclomethasone dipropionate (BDP) 400 micrograms/day for 7 mo on the linear growth and adrenal function of 94 children 7 to 9 yr of age. Height was measured at least monthly during treatment, and adrenal function assessed by overnight urinary cortisol at baseline and after 3 and 6 mo of treatment. Mean regressed daily growth was significantly decreased during the treatment period in the BDP-treated group, 0.79 versus 1.14 mm/wk (difference 0.35 mm/wk; 95% CI -0.46 to -0.25; p < 0.0001). At the end of the 7 mo, the BDP-treated children had grown significantly less than the children on placebo: mean of 2.66 versus 3.66 cm (difference 1.0 cm; 95% CI -1.36 to -0.64 cm; p < 0.0001). Growth was significantly decreased in both males and females. During a washout period of 4 mo, there was no significant catch-up growth. BDP had no effect on overnight urinary cortisol production. BDP at a dose taken by many children significantly decreases statural growth in children with mild asthma, and this effect is unlikely to be mediated through the hypothalamo-pituitary-adrenal axis.",
"At this time, no placebo-controlled studies in the clinical literature compare the efficacy and safety of the most widely prescribed oral inhaled corticosteroids when dosed at their recommended daily doses. This study compared the efficacy and safety of beclomethasone dipropionate (BDP) 336 microg/day administered by metered dose inhaler (MDI) alone, and triamcinolone acetonide (TA) 800 microg/day by MDI with a built-in tube extender in adults with persistent asthma.\n This 56-day, randomized, double-blind, double-dummy, placebo-controlled, multicenter trial was conducted in 328 adults with mild to moderately severe asthma (FEV1 50% to 90% of predicted while maintained on inhaled corticosteroids). Patients were seen at a baseline visit and on study days 28 and 56. Efficacy variables included pulmonary function tests, physician and patient assessments of asthma condition, and use of rescue medication.\n Statistically significant improvements from baseline in most efficacy measures were demonstrated for both active treatments versus placebo, and with the following exception were the same between active treatments: mean increase in FEV1 in the beclomethasone dipropionate group was statistically significantly greater than in the triamcinolone acetonide group on day 28. Throughout the study, BDP was statistically superior to TA with respect to mean change from baseline in total asthma symptom scores and for 3 of 8 weeks in reducing the mean average weekly use of rescue albuterol (the two active treatments were comparable for this variable at all other time points). Beclomethasone dipropionate and TA were comparable in safety.\n In adult patients with mild to moderately severe persistent asthma, treatment with BDP consistently conferred greater improvement from baseline in mean FEV1 than TA. This difference achieved statistical significance after 28 days of therapy but was not maintained to endpoint. Decreases in overall asthma symptom scores and in the use of rescue albuterol were statistically significantly greater for the BDP group compared with the TA group. Based on these findings, we conclude that BDP is at least as effective as TA in the treatment of persistent asthma in adults, and judged by some measures, may be superior.",
"The effects of twice daily inhaled beclomethasone dipropionate (BDP) at two dose levels (500 and 1,000 micrograms daily) on the airway responsiveness to inhaled histamine was evaluated by a randomized, single-blind, cross-over study in 10 patients with stable asthma. The 12-week study began with a 3-week run-in period of baseline treatment, which was continued unchanged throughout the study, and the two treatment periods were separated by a 3-week placebo period. Patients attended the laboratory every 3 weeks for spirometry and histamine inhalation tests to determine the provocative concentration of histamine causing a 20% fall in forced expiratory volume in 1 s (PC20 of FEV1). There was a similar significant improvement (p less than 0.05) in mean FEV1 after both treatments. There was no significant change in PC20 after treatment with 500 micrograms daily, the geometric mean being 0.587 mg/ml after the placebo period and 0.860 mg/ml after BDP treatment. There was a significant improvement in PC20 (1.930 mg/ml) after treatment with 1,000 micrograms BDP daily in comparison with the placebo and treatment periods with 500 micrograms BDP daily (p less than 0.001). These results suggest that higher doses than usual of inhaled BDP must be used to control airway responsiveness in asthmatics.",
"In a multicenter, randomized, double-blind study, inhaled beclomethasone dipropionate (BDP) 1,500 micrograms/day was compared to placebo in 43 chronic asthmatic patients uncontrolled by inhaled salbutamol and oral theophylline. During the prestudy period, a test of maximal steroid reversibility with oral prednisolone 0.5 mg/kg/day for 14 days was performed. The therapeutic response was measured over an 8-wk period as the ability to maintain the clinical improvement and the optimal pulmonary function induced by prednisolone. During the study, severe asthma exacerbation occurred in one (5%) of the 21 patients who received BDP and in 15 (78%) of the 22 patients who received placebo (p less than 0.001). In patients who received BDP, FEV1 and peak expiratory flow (PEF) remained above the optimal postprednisolone value, with a trend to improvement during the 8-wk study period. In patients who received placebo, FEV1 and PEF decreased and remained below the optimal value. We conclude that, in chronic asthma, inhaled BDP 1,500 micrograms/day maintains the optimal pulmonary function in addition to the clinical benefit induced by a short course of oral corticosteroids.",
"The phasing out of chlorofluorocarbons (CFCs) requires the development of an alternative non-ozone depleting propellant for use in pressurized metered dose inhalers (pMDIs). The present study assessed the effects on tolerability and efficacy of a switch from the currently available formulation containing the CFC propellants 11 and 12 to an alternative non-CFC formulation using the propellant hydrofluoroalkane (HFA) 134a in patients with mild to moderate asthma. After a 4-week run-in period during which patients received salbutamol 200 microg four times daily from a CFC pMDI, 547 patients were randomized to 12 weeks of treatment with salbutamol 200 microg four times daily administered from either an HFA 134a pMDI (Ventolin CFC-free; 277 patients) or CFC pMDI (Ventolin, 270 patients). At the end of this period, all patients then received a further 4 weeks of treatment with the same dose of salbutamol via a CFC pMDI (run-out period). On the basis that high doses of beta2-agonists are known to increase heart rate, change in heart rate was selected as the primary outcome variable. Small increases in heart rate were observed during the treatment period and these changes were comparable in both groups; the 90% confidence interval for the treatment differences was within the predefined limits for clinical equivalence (+/- 10 beats min(-1)). The incidence of adverse events was similar in both groups and there were no reports of paradoxical bronchospasm. Furthermore, daily PEF measurements showed comparability in terms of lung function. Symptom scores and use of additional bronchodilator were also similar in both groups. These results demonstrate that salbutamol (800 microg day(-1)), formulated with HFA 134a is equivalent to the current CFC formulation in terms of tolerability and efficacy.",
"We investigated the effect of 300 micrograms of inhaled beclomethasone dipropionate (BDP) daily on bronchial responsiveness to methacholine and pulmonary function of 22 subjects with asthma in a single-blind, crossover study. The severity of bronchial hyperresponsiveness lessened significantly during treatment with BDP (P < .01). No significant changes occurred in FEV1 or in the control value of airway conductance. We conclude that a 300-micrograms total daily dose of BDP is an efficacious treatment for patients with asthma. Because suppression of adrenal function and systemic adverse effects can occur in asthmatic patients treated with inhaled corticosteroids, especially children, long-term treatment with inhaled steroids should employ minimal daily doses necessary.",
"Inhaled corticosteroids provide first-line treatment for asthma. An advance to improve potency was to produce new molecules with increased glucocorticoid receptor affinity (eg, fluticasone propionate [FP]). An alternative is to deliver more medication to both the large and small airway inflammation of asthma by using an extrafine aerosol (eg, beclomethasone dipropionate extrafine aerosol [BDP-extrafinel).\n To demonstrate clinical equivalence of BDP-extrafine (400 microg daily) and FP (400 microg daily) in symptomatic asthmatic patients over the course of 6 weeks.\n This was a double-blind, double-dummy, parallel-group, multicenter, 6-week study in adults with asthma taking conventional FP 100 to 250 microg daily or equivalent, and displaying signs/symptoms of active disease requiring additional therapy.\n Eighty-eight patients were randomized to BDP-extrafine (and FP-placebo) and 84 to FP (and BDP-placebo). There were no significant differences between treatments with respect to symptom control, as evidenced by mean change from baseline in percentage days without asthma symptoms/nights without sleep disturbance observed at weeks 1 to 2, 3 to 4, or 5 to 6. Mean changes from baseline in AM PEFR at weeks 5 to 6 for BDP-extrafine (19.0) and FP (30.5) were equivalent (P = 0.022 for equivalence). There were significant (P < 0.001) within-treatment-group differences in mean change from baseline in AM PEFR at weeks 1 to 2 for both treatments. There was no difference in the incidence of patients reporting at least one adverse event during the study (BDP-extrafine 41%; FP 37%). Mean percentage change from baseline for AM plasma cortisol at week 6 was + 17.7% for BDP-extrafine and +4.2% for FP (P = 0.066 for difference).\n BDP-extrafine and FP at doses of 400 microg daily provided equivalent asthma control in patients with symptomatic asthma and exhibited similar safety profiles.",
"The effect of treatment with inhaled corticosteroids in patients with non-asthmatic chronic airflow obstruction is still disputed. Whether any physiological improvements seen are accompanied by changes in bronchial responsiveness and symptoms and quality of life is also still unclear.\n A sequential placebo controlled, blinded parallel group study investigating the effect of three weeks of treatment with inhaled beclomethasone dipropionate (BDP), 750 micrograms or 1500 micrograms twice daily, and oral prednisolone, 40 mg per day, was carried out in 105 patients with severe non-asthmatic chronic airflow obstruction (mean age 66 years, mean forced expiratory volume in one second (FEV1) 1.05 litres [40% predicted], geometric mean PD20 0.52 mumol). End points assessed were FEV1, forced vital capacity (FVC), and peak expiratory flow (PEF), bronchial responsiveness to inhaled histamine, and quality of life as measured by a formal quality of life questionnaire.\n Both doses of BDP produced equivalent, small, but significant improvements in FEV1 (mean 48 ml), FVC (mean 120 ml), and PEF (mean 12.4 l/min). The addition of oral prednisolone to the treatment regime in two thirds of the patients did not produce any further improvement in these parameters. Inhaled BDP produced a treatment response in individual patients (defined as an improvement in FEV1, FVC, or mean PEF of at least 20% compared with baseline values) more commonly than placebo (34% v 15%). The two doses of BDP were equally effective in this respect and again no further benefit of treatment with oral prednisolone was noted. Treatment with BDP for up to six weeks did not affect bronchial responsiveness to histamine. Small but significant improvements were seen in dyspnoea during daily activities, and the feeling of mastery over the disease.\n High dose inhaled BDP is an effective treatment for patients with chronic airflow obstruction not caused by asthma. Both objective and subjective measures show improvement. Unlike asthma, no improvement in bronchial responsiveness was detected after six weeks of treatment.",
"The aim of this study was to compare the efficacy safety and cost of Seretide (salmeterol/fluticasone propionate (Salm/FP), 50/250 microg bd) via Diskus with formoterol (Form; 12 microg bd) and budesonide (Bud; 800 microg bd) given concurrently (Form+Bud) via Turbuhaler in patients with moderate-to-severe asthma who were uncontrolled on existing corticosteroid therapy. The study used a randomised, double-blind, double-dummy, parallel-group design, consisting of a 2-week run-in period on current corticosteroid therapy (1000-1600 microg/day of BDP or equivalent) and a 12-week treatment period. Symptomatic patients (n = 428) with FEV1 of 50-85% predicted and increased symptom scores or reliever use during run-in were randomly allocated to receive either Salm/FP (50/250 microg bd) via a single Diskus inhaleror Form+Bud (12+800 microg bd) via separate Turbuhalers. Clinic, diary card and asthma-related health-care resource utilisation data were collected. Improvement in mean morning peak expiratory flow (PEFam was similar in the Salm/FP and Form+Bud groups. Both PEFam and mean evening PEF (PEFpm) increased by a clinically significant amount (>20 L/min) from baseline in both treatment groups. The mean rate of exacerbations (mild, moderate or severe) was significantly lower in the Salm/FP group (0.472) compared with the Form+Bud group (0.735) (ratio = 0.64; P < 0.001), despite the three-fold lower microgram inhaled corticosteroid dose in the Salm/FP group. Patients in the Salm/FP group also experienced significantly fewer nocturnal symptoms, with a higher median percentage of symptom-free nights (P = 0.04), nights with a symptom score <2 (P = 0.03), and nights with no awakenings (P = 0.02). Total asthma-related health-care costs were significantly lower in the Salm/FP group than the Form+Bud group (P<0.05). Both treatments were well tolerated, with a similar low incidence of adverse events. This study showed that in symptomatic patients with moderate-to-severe asthma, Salm/FP (50/250 microg bd), administered in a single convenient device (Diskus), was at least as effective as an approximately three-fold higher microgram corticosteroid dose of Bud (800 microg bd) given concurrently with Form (12 microg bd) in terms of improvement in PEFam, and superior at reducing exacerbations and nights with symptoms or night-time awakenings. Salm/FP was also the less costly treatment due primarily to lower hospitalisation and drug costs.",
"The objective of this study was to compare the efficacy and safety of fluticasone propionate (FP) (44 microg)/salmeterol (21 microg) delivered as two inhalations twice daily via a single hydrofluoroalkane (HFA 134a) metered dose inhaler (MDI) (FSC) with that of placebo HFA 134a (PLA), fluticasone propionate 44 microg chlorofluorocarbon (CFC) alone and salmeterol 21 microg CFC alone (S) in patients (n=360) with persistent asthma previously treated with beta2-agonists (short- or long-acting) or inhaled corticosteroids (ICS). After 12 weeks of treatment, patients treated with FSC had a significantly greater increase (p < or = 0.006) in mean FEV1 AUC(bl) compared with PLA, FP, or S. At end point, mean change from baseline in morning predose FEV1 for FSC (0.58 L) was significantly (p < or = 0.004) greater than PLA (0.14 L), FP (0.36 L), and S (0.25 L). Patients treated with FSC also had a significantly higher probability of remaining in the study without being withdrawn due to worsening asthma (2%) compared with those in the PLA (29%) and S (25%) groups (p < 0.001). Finally, treatment with FSC resulted in significantly (p < or = 0.007) greater improvements in morning and evening peak expiratory flow, need for rescue albuterol, and asthma symptom scores compared with FP, S, and PLA. The safety profile of FSC was also similar to FP or S alone. Initial maintenance treatment of the two main components of asthma, inflammation, and smooth muscle dysfunction (e.g., bronchoconstriction), with FSC results in greater overall improvements in asthma control compared with treatment of either individual component alone.",
"With the transition to hydrofluoroalkane-134a propellants in metered dose inhalers, it is important to consider the efficacy and safety profiles of formulations containing inhaled corticosteroids. We examined the airway and systemic effects of hydrofluoroalkane-134a fluticasone propionate (FLU-HFA) and beclomethasone dipropionate (BEC-HFA) at recommended labelled doses.\n Twenty mild to moderate asthmatics were randomised in crossover fashion to receive 6 weeks of 500 micro g/day followed by 1000 micro g/day FLU-HFA and BEC-HFA. Measurements were made at baseline after placebo run in and washout, and after each randomised treatment. The primary airway outcome for benefit was the dose of methacholine provoking a fall in forced expiratory volume in 1 second (FEV(1)) of 20% or more (methacholine PD(20)) and for systemic adverse effects was overnight urinary cortisol/creatinine (OUCC).\n For mean responses, both doses of BEC-HFA and FLU-HFA produced significant improvements in PD(20) compared with baseline. The improvement was not significantly greater with 1000 micro g/day FLU-HFA versus BEC-HFA, a 1.69 fold difference (95% CI 0.94 to 3.04). Both doses of BEC-HFA but not FLU-HFA caused significant suppression of OUCC compared with baseline, with significantly (p<0.05) lower values at 1000 micro g/day for BEC-HFA versus FLU-HFA (1.97 fold difference (95% CI 1.28 to 3.02)).\n There was no difference in the airway and systemic effects in patients with mild to moderate asthma between FLU-HFA and BEC-HFA at a dose of 500 micro g/day. At 1000 micro g/day there was increased systemic bioactivity with BEC-HFA compared with FLU-HFA, without any gain in airway efficacy.",
"This randomized, double-blind, parallel-group study compared the efficacy and tolerability of as-required salbutamol 100 microg administered from either a chlorofluorocarbon (CFC) pressurized metered dose inhaler (pMDI; Ventolin) or from a non-CFC hydrofluoroalkane (HFA) 134a pMDI (Ventolin CFC-free) in patients with mild to moderate asthma. All patients (n = 423) continued with their standard asthma therapy, and recorded their daily use of study medication, morning and evening peak expiratory flow (PEF) and symptom scores, throughout the 4-week treatment period. Clinic lung function was measured at 2-week intervals. The median daily use of inhaled study medication remained constant at four actuations per day throughout the study in both treatment groups and statistical analysis indicated that the two formulations were equivalent. Small improvements in both treatment groups were reported in mean morning and evening PEF, clinic forced expiratory volume in 1 sec and clinic PEF and there were no significant differences between the two groups. Both formulations were well tolerated. This study indicates that as-required salbutamol 100 microg administered via a HFA 134a pMDI is as effective and safe as the currently available CFC-propelled formulation.",
"During the 1970s, scientists suggested that the growing use of chlorofluorocarbons (CFCs) was contributing to depletion of the stratospheric ozone layer with potentially harmful results. A committee on the ozone layer organized the preparation of the Montreal Protocol. This protocol mandated the cessation of production and use of CFCs by January 1, 1996. The primary exemption to this ban is for the use of CFCs as propellants in metered dose inhalers (MDIs) for the treatment of asthma. Suitable replacement hydrofluoroalkane (HFA) propellants, such as HFA-134a, for use in MDIs have been identified. Albuterol, a selective beta-adrenergic agonist, currently widely available for inhalation asthma therapy, has been reformulated in HFA-134a (Proventil HFA). OBJECTIVE; To compare the efficacy of Proventil HFA to Ventolin, Proventil, and placebo (HFA-134a) MDI in protecting asthmatic patients from exercise-induced bronchoconstriction.\n This was a randomized, single-blind, placebo-controlled, 4-period crossover study of asthmatic patients with documented exercise-induced broncho-constriction. Twenty patients self administered two puffs of either Proventil HFA, Ventolin, Proventil or placebo, from an MDI, 30 minutes prior to performing a standardized exercise challenge at the study site. Spirometry was performed predose and 5, 10, 15, 30, 45, 60, 75, and 90 minutes after completion of the exercise challenge. Heart rate and blood pressure were measured just prior to spirometry and a 12-lead ECG was performed 15 minutes after completion of the exercise challenge for measurement of the QT corrected interval.\n The primary efficacy variable was the smallest percent change from the predose FEV1 following exercise. The smallest percent change from predose FEV1 for Proventil HFA was 2.0 +/- 9.9 SD, similar to the 2.0 +/- 11.4 SD for Ventolin, and the 3.6 +/- 10.2 SD for Proventil. The smallest percent change from predose FEV1 for each of the active treatments was significantly different from placebo, -23.7 +/- 14.5. Twelve of the patients had a > or = 20% fall in FEV1 post-exercise with placebo pretreatment, but only 1, 1, and 0 had > or = 20% FEV1 falls after treatment with Proventil HFA, Ventolin, and Proventil respectively. Changes in heart rate, blood pressure and QT corrected interval were similar for the three active treatments following exercise.\n Proventil HFA provides protection against exercise-induced bronchoconstriction comparable to Ventolin and Proventil and protection superior to placebo. Proventil HFA has a safety profile similar to Ventolin when used to prevent exercise-induced bronchoconstriction.",
"This study was designed primarily to assess the safety and tolerability of fluticasone propionate (FP) 1 mg day-1 by comparison with beclomethasone dipropionate (BDP) 2 mg day-1 over a 12-month study period. Lung function data were also recorded and used to determine whether the potency ratio between the two inhaled corticosteroids observed in previous studies was maintained in the long-term. Two hundred and thirteen patients with an established clinical history of severe chronic asthma and who were currently receiving between 1000 micrograms and 2000 micrograms day-1 of inhaled steroids were randomized to treatment in a ratio of 3:1 for FP:BDP (159 patients FP; 54 patients BDP), both via metered dose inhalers. Both treatments were well tolerated with a similar adverse event profile. No unexpected adverse events were recorded. Most adverse events were related to the patients' asthma, an intercurrent infection or underlying atopy. The incidence of pharmacologically predictable adverse events was equally low in both treatment groups as was the incidence of events suggestive of systemic steroid effect. Mean serum cortisol levels remained within the normal range at all visits for both treatments. At 12 months, however, the mean cortisol levels for the FP group had risen 4% above the baseline value but had dropped 15% below for the BDP group, giving a ratio of FP:BDP of 1.22; P = 0.01; 95% confidence limits (CL) 1.05-1.43. Fluticasone propionate 1 mg day-1 was at least as effective as BDP 2 mg day-1 in improving lung function (PEF, FEV1 and FVC) over this period. Moreover, the difference in FEV1 values at 6 months was significantly greater for the FP group than for the BDP group (P = 0.04; difference = 0.12 1; 95% CL = 0.01, 0.24 1). The difference between treatments in the amount of FEV1 reversibility was also significantly greater for FP at 12 months (difference in treatments = -3%; 95% CL = - 7-0%; P = 0.044). This study supports previous studies and suggests that FP is likely to be of benefit in the long-term treatment of chronic severe asthma.",
"A study was done to compare the efficacy and safety of the coprescription of salmeterol 50 microgram twice daily or 100 microgram twice daily with beclomethasone dipropionate (BDP) 500 micrograms twice daily (SALM 50 and SALM 100) with BDP 1,000 microgram twice daily (BDP 1,000) in patients with asthma not controlled by BDP 500 microgram twice daily (or the equivalent). Following a run-in period, 738 patients at 72 centers were randomized to treatment for 24 wk in a double-blind, parallel-group study during which they maintained a daily record of peak expiratory flow rates (PEFRs) and symptom scores. At about 40 of the centers, bronchial hyperresponsiveness (BHR) to histamine was measured during and at 3 and 14 d after stopping treatment. Both groups taking salmeterol showed an improvement of more than 45 L/min in their morning PEFR and 30 L/min in their evening PEFR, compared with respective improvements of 16 L/min and 6 L/min in the group taking BDP 1,000. Both the SALM 50 and SALM 100 groups had a significantly increased percentage of symptom-free and rescue-free days and nights compared with the BDP 1,000 group, and there was no difference between the two salmeterol groups. None of the treatments altered BHR. Exacerbation rates did not differ among the three groups. We conclude that in this selected group of symptomatic patients taking BDP 500 micrograms twice daily, the addition of salmeterol provides better improvement in lung function and symptom control, without altering BHR or increasing exacerbation rates, than does doubling the dose of BDP.",
"Studies in adults revealed that addition of salmeterol to a moderate dose of inhaled corticosteroid resulted in better symptom control and higher PEF compared with doubling the dose of inhaled corticosteroid. The aim of this three group study was to compare the effects of a moderate dose of beclomethasone, the same dose of beclomethasone with salmeterol, and a doubling dose of beclomethasone on lung function and symptoms in children with moderate asthma. A total of 177 children already treated with inhaled corticosteroids, were randomized in a double-blind parallel study either to salmeterol 50 microg twice daily (BDP400+salm), beclomethasone 200 microg twice daily (BDP800), or placebo (BDP400) in addition to beclomethasone 200 microg twice daily. No significant differences between groups were found in FEV1, PD20 methacholine, symptom scores, and exacerbation rates after 1 yr. Salmeterol resulted in slightly better PEF in the first months of treatment. FEV1, and PD20 methacholine significantly improved in all groups. After 1 yr mean changes in FEV1, percent predicted were 4.3% (95% CI 1.3; 7.2), 5.8% (95% CI 2.9; 8.7), and 4.3% (95% CI 2.1; 6.5) for BDP400+salm, BDP800, and BDP400, respectively. Changes in airway responsiveness were 0.60 (95% CI 0.05; 1.14), 1.30 (95% CI 0.73; 1. 87), and 0.80 (95% CI 0.33; 1.27) doubling doses. Growth was significantly slower in the BDP800 group. We conclude that no additional benefit was found of adding either salmeterol or more beclomethasone to a daily dose of 400 microg beclomethasone in this group of children with excellent compliance of medication.",
"We wanted to evaluate whether treatment with an inhaled corticosteroid and an inhaled long-acting beta2-agonist is more effective than an inhaled corticosteroid alone for patients using as-needed albuterol who are initiating maintenance treatment.\n To compare the efficacy and safety of twice-daily fluticasone propionate (FP) 88 microg and salmeterol 42 microg combined in a chlorofluorocarbon (CFC)-free (hydrofluoroalkane 134a) metered-dose inhaler (MDI) with the individual agents alone, each delivered through an MDI containing CFC propellants, in patient with persistent asthma previously uncontrolled with as-needed short-acting beta2-agonists alone.\n Patients with asthma (n = 283) were randomized to twice-daily treatment for 12 weeks with FP 88 microg combined with salmeterol 42 microg (FSC) in a CFC-free MDI or the individual components alone from CFC-containing MDIs.\n At endpoint, mean change from baseline in morning predose forced expiratory volume in 1 second was significantly (P < or = 0.016) greater with FSC (0.69 L) compared with FP (0.51 L) or salmeterol (0.47 L). Fewer patients treated with FSC withdrew due to worsening asthma (1%) compared with FP (3%) or salmeterol (8%; P = 0.024). FSC significantly increased (P < or = 0.002) morning and evening peak expiratory flow rate at endpoint (66.5 and 51.5 L/min, respectively) compared with FP (43.0 and 29.9 L/min, respectively) and salmeterol (29.2 and 21.6 L/min, respectively). In addition, asthma symptom scores were reduced, and percentages of days with no asthma symptoms increased in all treatment groups.\n Treatment with FSC in a CFC-free MDI is more effective than FP or salmeterol alone in asthma patients who are symptomatic taking short-acting beta2-agonists alone.",
"To compare the benefits and adverse reactions of theophylline and beclomethasone (BDP) in the long-term control of mild to moderate chronic asthma in children.\n Multicentered, double-blind, double-placebo, randomized, controlled trial.\n One hundred ninety-five children between the ages of 6 and 16 years with mild to moderate asthma.\n Treatment with either BDP, 84 micrograms four times a day, or sustained-release theophylline administered twice daily in doses adjusted for optimum control of symptoms.\n Daily diary record of symptoms, peak flow rates, supplemental bronchodilator and glucocorticoid treatment, doctor and hospital visits, absence from work and school, and side effects.\n Aerosol BDP and sustained-release theophylline were effective primary treatments for mild to moderate chronic asthma. Beclomethasone resulted in comparable symptom control with less bronchodilator use and fewer courses of systemic steroids than did theophylline. Side effects were observed significantly more frequently with theophylline than with BDP. Growth velocity suppression was noted with BDP and was more pronounced in boys. Suppression was not associated with alterations in cortisol measurements either at baseline or following stimulation.\n Both theophylline and BDP are effective therapy for mild to moderate asthma. Caution must be used with the administration of BDP in children because of possible growth velocity suppression.",
"A total of 102 patients had their asthma treatment with beclomethasone dipropionate (BDP) optimized in order to achieve the best possible control of symptoms. Thereafter, the BDP doses were gradually reduced over a 2-year period (1988-90) to the lowest possible without deterioration of their asthmatic condition. In the beginning of 1990, treatment was changed in 76 patients (group A) to the nearest possible dose of budesonide delivered via Turbuhaler. Twenty-six randomly selected patients (25% of the study population; group B) continued treatment with BDP. In both groups, dose reductions were tried during 1990-2 every third month as long as the patients remained symptom-free and without significant decreases in FEV1 or PEF. In group A, the maintenance dose could be reduced from 1003.9 +/- 325.4 micrograms BDP (mean +/- SD) to 602.9 +/- 454.4 micrograms budesonide Turbuhaler (P < 0.001). In group B, no significant dose reduction was possible; the mean dose was +/- SD 1067.3 +/- 36.6 micrograms in 1990, and 1019.2 +/- 324.7 micrograms in 1992. The results indicate that, in efficacy, 0.6 mg budesonide Turbuhaler corresponds to approximately 1.0 mg BDP with volumatic spacer. This difference is probably due to an improved pulmonary delivery of budesonide with Turbuhaler.",
"Asthma is a chronic inflammatory disorder of the airways that is characterized by infiltration of many inflammatory cells into the bronchial mucosa. We compared the effects of ketotifen, disodium cromoglycate (DSCG), and beclomethasone dipropionate (BDP) on inflammatory cells in the bronchial mucosa and on the asthma symptoms of patients with atopic asthma. In this 12-week parallel study, 32 patients were randomly allocated to either the ketotifen group (2 mg day-1, n = 13), DSCG group (8 mg day-1, n = 9) or BDP (400 micrograms day-1, n = 10). Each subject recorded daily asthma symptoms and peak expiratory flow (PEF). Before and after treatment, pulmonary function and bronchial responsiveness to methacholine were evaluated, and fibreoptic bronchoscopy and biopsy were performed before and after treatment. Biopsy specimens were obtained by bronchoscopy. We performed immunohistochemistry using specific monoclonal antibodies for activated eosinophils (EG2), mast cells (AA1), and T cells (CD3, CD4, and CD8). Our clinical findings showed significant improvement in symptom score and bronchial responsiveness (P < 0.01) each) in all groups. Both the DSCG and the BDP groups had significantly better symptom scores than the ketotifen group (P < 0.05, both groups). PEF significantly increased in the DSCG group in comparison to the ketotifen (P < 0.01) and BDP (P < 0.05) groups, FEV1% increased significantly in the DSCG (P < 0.01) and BDP (P < 0.05) groups in comparison to the ketotifen group. Compared with their baseline values, treatment significantly decreased EG2+ activated eosinophils, and CD3+ and CD4+ T cells, in each group (P < 0.01). Both the DSCG (P < 0.05) and the BDP groups (P < 0.01) exhibited significant decreases in AA1+ mast cell count, but this was not observed in the ketotifen group. Comparing before- and after-treatment values, only the DSCG group exhibited a significant decrease in the number of CD8+ T cells (P < 0.01). Ketotifen, DSCG, and BDP all showed anti-inflammatory activity as determined by examination of the bronchial mucosa of asthmatic patients; and both the DSCG and BDP groups had better clinical responses than the ketotifen group.",
"This study compares the safety and efficacy of HFA 134a salbutamol sulfate (Airomir in the 3M CFC-free system [3M Pharmaceuticals]) and CFC 11/12 salbutamol (Ventolin [Allen & Hanburys]) in a cumulative dose-response (1, 1, 2, 4, 8 inhalations at 30-min intervals) study in asthmatic patients.\n Randomized, single-blind, two-period cross-over study.\n Twenty-four stable mild to moderate asthmatics.\n At all cumulative inhalations, the changes in FEV1 (absolute, percent, and percent predicted) and FVC were equivalent. There was also no significant difference in heart rate, serum potassium level, BP, 12-lead ECG, Holter monitor recordings, or adverse events. Both HFA 134a salbutamol sulfate and CFC 11/12 salbutamol displayed a significant dose-response for FEV1, FEF25-75%, FVC, serum potassium, heart rate, and systolic BP.\n HFA 134a salbutamol sulfate and CFC 11/12 salbutamol produced clinically and statistically similar airway responses and side effects. These results indicate that HFA 134a salbutamol sulfate would be a safe and effective substitute for CFC 11/12 salbutamol.",
"One hundred and twenty four patients with severe asthma requiring maintenance treatment with oral corticosteroids were included in a multicentre, double-blind, randomized study comparing the effects of inhaled beclomethasone dipropionate (BDP) (250 micrograms.puff-1), beginning with 1,000 micrograms daily, vs placebo (P). Pulmonary function was assessed and dosage of prednisone and BDP (or P) were adjusted every 15 days according to a clinical score. Our results showed, after 3 months: 1) A greater drop-out rate in the P group than in the BDP group (36 vs 6%, respectively, p less than 0.01); 2) A total weaning from prednisone in 76% of patients in the BDP group (mean BDP dosage = 1,270 +/- 340 micrograms.day-1, mean +/- SD), vs 34% in the P group (p less than 0.001). The mean daily dosage of prednisone was reduced from 17 +/- 7.5 mg to 3.1 +/- 7.4 mg in the BDP group vs 15.6 +/- 7.7 mg to 9.1 +/- 9.4 mg in the P group (p less than 0.001) without any relationship between the steroid-sparing effect and the initial dosage of prednisone; 3) Mean change in forced expiratory volume in one second (FEV1) was +7 +/- 21% from the initial value in the BDP group vs -6 +/- 20% in the P group; p less than 0.01. Thus, in patients with severe asthma requiring oral corticosteroids, high-dose BDP has an important oral steroid-sparing effect not related to the initial dosage of oral steroids and allows a better control of airway obstruction than oral corticosteroids alone.",
"The objective of this study was to compare the clinical effects of beclomethasone dipropionate (BDP) and budesonide in asthmatic children using two common ways of administration. Twenty-one children, aged 4-14 years, who regularly used inhaled corticosteroids for their control of asthma were included in the study. The drugs were studied by using a double-blind randomized cross-over design trial with a single-blind placebo period at the end. Each period lasted 3 weeks. The dosage was 100 micrograms b.i.d. for both drugs. Budesonide was administered via a spacer inhaler (Inhalet), and beclomethasone dipropionate via a standard actuator. Compared with placebo, both drugs significantly improved PEFR values for morning (20% for budesonide and 14% for BDP) and evening (14% for budesonide and 9% for BDP). Both morning and/or evening peak flows were significantly higher during the budesonide treatment as compared with the BDP treatment. In comparison with the placebo period, FEV1.0 was significantly improved with budesonide but not with BDP. Plasma cortisol, WBC counts, differential and eosinophilia counts in blood were determined at the beginning and the end of each period. All of the values except for the eosinophil counts were within normal ranges. Candida was looked for but not found in any case. No other adverse effects were registered. For most of the children, a deterioration of the state of their asthma and increased need for concomitant therapy during the placebo period confirmed their steroid dependence. The number of administrations with concomitant anti-asthmatic therapy increased during placebo by 61% as compared with the budesonide therapy, and by 40% compared with the BDP therapy.",
"Combined therapy with inhaled corticosteroids (ICSs) and long-acting beta(2)-adrenoceptor agonists (LABAs) is the recommended approach for the treatment of patients with asthma that is uncontrolled on ICSs alone. Additional studies are needed to assess the safety and efficacy of combination treatment with ICSs and LABAs in patients with mild asthma. The aim of this study was to compare the efficacy and tolerability of once-daily salmeterol/fluticasone propionate combination (SFC) with once-daily fluticasone propionate (FP) over a 12-week treatment period in patients with mild persistent asthma.\n This was a randomized, double-blind, placebo-controlled, parallel-group, multicentre study carried out in primary care or at a hospital outpatient department and included patients 12-79 years of age with mild persistent asthma (n = 458). After a 2-week run-in period, patients were randomized to receive SFC 50 microg/100 microg (n = 149), FP 100 microg (n = 154) or placebo (n = 155) once daily in the morning for 12 weeks. The primary efficacy endpoint was patient-recorded pre-dose mean morning peak expiratory flow (PEF). Other assessments included asthma symptom scores, use of rescue medication and investigator-recorded exacerbations. Lung function was measured and assessed during clinic visits.\n For the primary efficacy endpoint of mean change in morning PEF, SFC achieved significantly greater increases from baseline than both placebo (difference in adjusted means 23 L/min; 95% CI 15.0, 30.3; p < 0.001) and FP (difference in adjusted means 14 L/min; 95% CI 6.3, 21.7; p < 0.001). Compared with those who received FP, patients in the SFC group demonstrated significantly greater improvements in mean evening PEF (95% CI 11.7, 28.1; p < 0.001), forced expiratory volume in 1 second (95% CI 0.093, 0.257; p < 0.001), forced expiratory flow between 25% and 75% of forced vital capacity (95% CI 0.242, 0.617; p < 0.001), the percentage of symptom-free days (95% CI 0.34, 0.87; p = 0.011), and the percentage of rescue medication-free days (95% CI 0.34, 0.90; p = 0.018). During weeks 5-12, 52% of patients in the SFC group achieved 'well controlled' asthma, compared with 42% and 26% of patients in the FP and placebo groups, respectively. Only one patient (receiving placebo) had a severe asthma exacerbation during the study; the frequency of adverse events was similar across the three treatment groups.\n Once-daily SFC 50 microg/100 microg provided significantly greater improvements in lung function and in asthma symptoms than once-daily FP 100 microg alone in patients with mild persistent asthma. However, twice-daily treatment with either SFC or ICSs plus short acting beta(2)-adrenoceptor agonists could be required to achieve guideline-defined asthma control in some patients."
] |
This review has quantified the efficacy of CFC-BDP and HFA-BDP in the treatment of chronic asthma and strongly supports its use. Current asthma guidelines recommend titration of dose to individual patient response, but the published data provide little support for dose titration above 400 mcg/d in patients with mild to moderate asthma. There are insufficient data to draw any conclusions concerning dose-response in people with severe asthma.
|
CD001718
|
[
"3512622",
"354331",
"7172160",
"354325",
"345313",
"4994687",
"4608506",
"5030483",
"4599422",
"11054193"
] |
[
"A controlled clinical trial of fluspirilene, a long-acting injectable neuroleptic, in schizophrenic patients with acute exacerbation.",
"Double-blind therapeutic evaluation of fluspirilene compared with fluphenazine decanoate in chronic schizophrenics.",
"A double-blind comparison of fluspirilene and fluphenazine decanoate in schizophrenia.",
"A double-blind clinical evaluation of different dose intervals with fluspirilene (IMAP).",
"A comparative controlled trial of pimozide and fluphenazine decanoate in the continuation therapy of schizophrenia.",
"A controlled study of fluspirilene in chronic schizophrenia.",
"A multicenter controlled trial of fluspirilene and fluphenazine enanthate in chronic schizophrenic syndromes.",
"Fluspirilene and pipothiazine undecylenate, two long-acting injectable neuroleptics. A double-blind controlled trial in residual schizophrenia.",
"Controlled trial of depot fluphenazine in out-patient schizophrenics.",
"Randomized trial of inhaled flunisolide versus placebo among asthmatic patients discharged from the emergency department."
] |
[
"A 4-week double-blind controlled clinical trial was carried out in which fluspirilene, an injectable diphenylbutylpiperidine neuroleptic given weekly, was compared to chlorpromazine in the treatment of 40 newly admitted schizophrenic patients with acute exacerbation. Similar therapeutic improvement was obtained with both drugs, but men needed a significantly higher mean dose of fluspirilene (23 mg/week) than women (13 mg/week). Fluspirilene induced more parkinsonism than chlorpromazine, but less drowsiness, dizziness, and dry mouth. The difference between the sexes in the potency of fluspirilene and its greater potential to induce parkinsonism may be related to its lesser presynaptic and D1-dopamine receptor blocking properties. The low incidence of autonomic side effects confirms the relative specificity of fluspirilene for dopamine receptors.",
"Fifty chronic schizophrenics were randomly assigned to a 16-week treatment either with fluspirilene or with fluphenazine decanoate. The aim of the study was to compare the antipsychotic action and the side effects of the two neuroleptics. Fluphenazine decanoate caused more side effects and the difference between the two groups was statistically significant in the items tremor, severe extrapyramidal effects and parkinsonism. More patients in the fluspirilene group (nine patients) compared with only three in the fluphenazine decanoate group remained free of side effects during the whole trial. Judged from the BPRS fluspirilene proved an equally potent neuroleptic with fluphenazine decanoate although statistically significant improvement has been obtained in more items of the scale in the fluspirilene group. The improvement in the NOSIE-30 was much more clear in the fluspirilene group. Although Clinical Global Impressions of the investigators and the nursing personnel favored fluspirilene, the differences between the two groups were not statistically significant.",
"A double-blind comparison of fluspirilene and fluphenazine decanoate in 28 schizophrenic patients over six months showed equal improvement and the same incidence of side-effects in each group of patients. It would be expected from the literature that a better ratio of therapeutic to side-effects would appear with fluspirilene than with fluphenazine. The absence of such an effect in this study may be attributable to an initial lack of familiarity by the investigators with the use of fluspirilene, indicating an important potential variable in the comparison of a new drug with an established one.",
"The possibility of a biweekly dose of fluspirilene, without deterioration of the clinical picture, was investigated in a group of 34 chronic schizophrenic patients. There were no significant clinical difference between the patients receiving fluspirilene every week and the patients receiving it every two weeks. Therefore it is possible to give fluspirilene in individually adjusted doses with a dose interval of 14 days in stabilized patients.",
"Evidence from a controlled, comparative trial indicates that oral pimozide is clinically at least as effective as depot injections of fluphenazine decanoate in the continuation therapy of a group of schizophrenic patients discharged from hospital. The administration of pimozide was associated with fewer unwanted effects. The implications of the findings are discussed.",
"nan",
"nan",
"nan",
"nan",
"Inhaled corticosteroids (ICs) improve airflow and decrease symptoms in patients with chronic asthma. We examined whether high-dose inhaled flunisolide would have similar benefits after an emergency department visit for acute asthma.\n Over a 16-month period at one inner-city ED, we documented 551 eligible patients (acute asthma; age 18 to 50 years; no ICs in past week; no oral corticosteroids in past month; and peak expiratory flow rate [PEFR] <70% of predicted value after first beta-agonist treatment); 104 patients agreed to participate. At ED discharge, all patients were given prednisone 40 mg/d for 5 days and inhaled beta-agonists as needed and were randomly assigned to receive high-dose inhaled flunisolide 2 mg/d (n=51) or placebo (n=53). Patients were telephoned daily and asked to return for PEFR measurement at 3, 7, 12, 21, and 24 days.\n Despite precautions, 28% (16 receiving flunisolide and 13 receiving placebo) of patients were completely lost to follow-up, 2 patients had only one follow-up (day 3), 2 patients receiving flunisolide withdrew because of medication-related bronchospasm, and 4 patients in each group experienced relapse. Among the 63 remaining patients, we found no difference between flunisolide and placebo at day 24 follow-up in percent predicted PEFR (87% versus 83% on day 24, P =.36; difference 4%, 95% confidence interval [CI] -5% to 13%). Nocturnal wheezing and nocturnal albuterol inhaler use was higher among patients receiving flunisolide than those receiving placebo on day 24 (48% versus 18% for nocturnal wheezing, P =.01; mean difference 30%, 95% CI 11% to 49%; 3.8 versus 1.4 nocturnal albuterol puffs, P =.03; mean difference 2.4 puffs, (95% CI 0.2 to 4). Levels of dyspnea, cough, and overall well-being were similar between the flunisolide and placebo groups.\n Addition of high-dose inhaled flunisolide to standard therapy does not benefit inner-city patients with acute asthma in the first 24 days after ED discharge. Airway inflammation during acute asthma may require higher doses or more potent anti-inflammatory agents."
] |
Participant numbers in each comparison were small and we found no clear differences between fluspirilene and oral medication or other depots. The choice of whether to use fluspirilene as a depot medication and whether it has advantages over other depots cannot, at present, be informed by trial-derived data. Well-conducted and reported randomised trials are still needed to inform practice.
|
CD004816
|
[
"15111846",
"15325833",
"16034009",
"17283260",
"11277825",
"12814710",
"12479764",
"15326073",
"16801565",
"16899775",
"12814712",
"2861311",
"7968073",
"15562202"
] |
[
"Reduction in cardiovascular events after vascular surgery with atorvastatin: a randomized trial.",
"Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial.",
"Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis.",
"Effects of intensive versus moderate lipid-lowering therapy on myocardial ischemia in older patients with coronary heart disease: results of the Study Assessing Goals in the Elderly (SAGE).",
"Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial.",
"MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial.",
"Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT).",
"Early statin treatment in patients with acute coronary syndrome: demonstration of the beneficial effect on atherosclerotic lesions by serial volumetric intravascular ultrasound analysis during half a year after coronary event: the ESTABLISH Study.",
"Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes: the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in non-insulin-dependent diabetes mellitus (ASPEN).",
"High-dose atorvastatin after stroke or transient ischemic attack.",
"Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial.",
"Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly trial.",
"Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)",
"Two-year statin therapy does not alter the progression of intima-media thickness in patients with type 2 diabetes without manifest cardiovascular disease."
] |
[
"This prospective, randomized, placebo-controlled, double-blind clinical trial was performed to analyze the effect of atorvastatin compared with placebo on the occurrence of a 6-month composite of cardiovascular events after vascular surgery. Cardiovascular complications are the most important cause of perioperative morbidity and mortality among patients undergoing vascular surgery. Statin therapy may reduce perioperative cardiac events through stabilization of coronary plaques.\n One hundred patients were randomly assigned to receive 20 mg atorvastatin or placebo once a day for 45 days, irrespective of their serum cholesterol concentration. Vascular surgery was performed on average 30 days after randomization, and patients were prospectively followed up over 6 months. The cardiovascular events studied were death from cardiac cause, nonfatal myocardial infarction, unstable angina, and stroke.\n Fifty patients received atorvastatin, and 50 received placebo. During the 6-month follow-up primary end points occurred in 17 patients, 4 in the atorvastatin group and 13 in the placebo group. The incidence of cardiac events was more than three times higher with placebo (26.0%) compared with atorvastatin (8.0%; P =.031). The risk for an event was compared between the groups with the Kaplan-Meier method, as event-free survival after vascular surgery. Patients given atorvastatin exhibited a significant decrease in the rate of cardiac events, compared with the placebo group, within 6 months after vascular surgery (P =.018).\n Short-term treatment with atorvastatin significantly reduces the incidence of major adverse cardiovascular events after vascular surgery.",
"Type 2 diabetes is associated with a substantially increased risk of cardiovascular disease, but the role of lipid-lowering therapy with statins for the primary prevention of cardiovascular disease in diabetes is inadequately defined. We aimed to assess the effectiveness of atorvastatin 10 mg daily for primary prevention of major cardiovascular events in patients with type 2 diabetes without high concentrations of LDL-cholesterol.\n 2838 patients aged 40-75 years in 132 centres in the UK and Ireland were randomised to placebo (n=1410) or atorvastatin 10 mg daily (n=1428). Study entrants had no documented previous history of cardiovascular disease, an LDL-cholesterol concentration of 4.14 mmol/L or lower, a fasting triglyceride amount of 6.78 mmol/L or less, and at least one of the following: retinopathy, albuminuria, current smoking, or hypertension. The primary endpoint was time to first occurrence of the following: acute coronary heart disease events, coronary revascularisation, or stroke. Analysis was by intention to treat.\n The trial was terminated 2 years earlier than expected because the prespecified early stopping rule for efficacy had been met. Median duration of follow-up was 3.9 years (IQR 3.0-4.7). 127 patients allocated placebo (2.46 per 100 person-years at risk) and 83 allocated atorvastatin (1.54 per 100 person-years at risk) had at least one major cardiovascular event (rate reduction 37% [95% CI -52 to -17], p=0.001). Treatment would be expected to prevent at least 37 major vascular events per 1000 such people treated for 4 years. Assessed separately, acute coronary heart disease events were reduced by 36% (-55 to -9), coronary revascularisations by 31% (-59 to 16), and rate of stroke by 48% (-69 to -11). Atorvastatin reduced the death rate by 27% (-48 to 1, p=0.059). No excess of adverse events was noted in the atorvastatin group.\n Atorvastatin 10 mg daily is safe and efficacious in reducing the risk of first cardiovascular disease events, including stroke, in patients with type 2 diabetes without high LDL-cholesterol. No justification is available for having a particular threshold level of LDL-cholesterol as the sole arbiter of which patients with type 2 diabetes should receive statins. The debate about whether all people with this disorder warrant statin treatment should now focus on whether any patients are at sufficiently low risk for this treatment to be withheld.",
"Statins reduce the incidence of cardiovascular events in persons with type 2 diabetes mellitus. However, the benefit of statins in such patients receiving hemodialysis, who are at high risk for cardiovascular disease and death, has not been examined.\n We conducted a multicenter, randomized, double-blind, prospective study of 1255 subjects with type 2 diabetes mellitus receiving maintenance hemodialysis who were randomly assigned to receive 20 mg of atorvastatin per day or matching placebo. The primary end point was a composite of death from cardiac causes, nonfatal myocardial infarction, and stroke. Secondary end points included death from all causes and all cardiac and cerebrovascular events combined.\n After four weeks of treatment, the median level of low-density lipoprotein cholesterol was reduced by 42 percent among patients receiving atorvastatin, and among those receiving placebo it was reduced by 1.3 percent. During a median follow-up period of four years, 469 patients (37 percent) reached the primary end point, of whom 226 were assigned to atorvastatin and 243 to placebo (relative risk, 0.92; 95 percent confidence interval, 0.77 to 1.10; P=0.37). Atorvastatin had no significant effect on the individual components of the primary end point, except that the relative risk of fatal stroke among those receiving the drug was 2.03 (95 percent confidence interval, 1.05 to 3.93; P=0.04). Atorvastatin reduced the rate of all cardiac events combined (relative risk, 0.82; 95 percent confidence interval, 0.68 to 0.99; P=0.03, nominally significant) but not all cerebrovascular events combined (relative risk, 1.12; 95 percent confidence interval, 0.81 to 1.55; P=0.49) or total mortality (relative risk, 0.93; 95 percent confidence interval, 0.79 to 1.08; P=0.33).\n Atorvastatin had no statistically significant effect on the composite primary end point of cardiovascular death, nonfatal myocardial infarction, and stroke in patients with diabetes receiving hemodialysis.",
"Clinical trials have demonstrated that, compared with placebo, intensive statin therapy reduces ischemia in patients with acute coronary syndromes and in patients with stable coronary artery disease. However, no studies to date have assessed intensive versus moderate statin therapy in older patients with stable coronary syndromes.\n A total of 893 ambulatory coronary artery disease patients (30% women) 65 to 85 years of age with > or = 1 episode of myocardial ischemia that lasted > or = 3 minutes during 48-hour ambulatory ECG at screening were randomized to atorvastatin 80 mg/d or pravastatin 40 mg/d and followed up for 12 months. The primary efficacy parameter (absolute change from baseline in total duration of ischemia at month 12) was significantly reduced in both groups at month 3 and month 12 (both P<0.001 for each treatment group) with no significant difference between the treatment groups. Atorvastatin-treated patients experienced greater low-density lipoprotein cholesterol reductions than did pravastatin-treated patients, a trend toward fewer major acute cardiovascular events (hazard ratio, 0.71; 95% confidence interval, 0.46, 1.09; P=0.114), and a significantly greater reduction in all-cause death (hazard ratio, 0.33; 95% confidence interval, 0.13, 0.83; P=0.014).\n Compared with moderate pravastatin therapy, intensive atorvastatin therapy was associated with reductions in cholesterol, major acute cardiovascular events, and death in addition to the reductions in ischemia observed with both therapies. The contrast between the therapies' differing efficacy for major acute cardiovascular events and death and their nonsignificant difference in efficacy for reduction of ischemia suggests that low-density lipoprotein cholesterol-lowering thresholds for ischemia and major acute cardiovascular events may differ. The Study Assessing Goals in the Elderly (SAGE) demonstrates that older men and women with coronary artery disease benefit from intensive statin therapy.",
"Patients experience the highest rate of death and recurrent ischemic events during the early period after an acute coronary syndrome, but it is not known whether early initiation of treatment with a statin can reduce the occurrence of these early events.\n To determine whether treatment with atorvastatin, 80 mg/d, initiated 24 to 96 hours after an acute coronary syndrome, reduces death and nonfatal ischemic events.\n A randomized, double-blind trial conducted from May 1997 to September 1999, with follow-up through 16 weeks at 122 clinical centers in Europe, North America, South Africa, and Australasia.\n A total of 3086 adults aged 18 years or older with unstable angina or non-Q-wave acute myocardial infarction.\n Patients were stratified by center and randomly assigned to receive treatment with atorvastatin (80 mg/d) or matching placebo between 24 and 96 hours after hospital admission.\n Primary end point event defined as death, nonfatal acute myocardial infarction, cardiac arrest with resuscitation, or recurrent symptomatic myocardial ischemia with objective evidence and requiring emergency rehospitalization.\n A primary end point event occurred in 228 patients (14.8%) in the atorvastatin group and 269 patients (17.4%) in the placebo group (relative risk [RR], 0.84; 95% confidence interval [CI], 0.70-1.00; P =.048). There were no significant differences in risk of death, nonfatal myocardial infarction, or cardiac arrest between the atorvastatin group and the placebo group, although the atorvastatin group had a lower risk of symptomatic ischemia with objective evidence and requiring emergency rehospitalization (6.2% vs 8.4%; RR, 0.74; 95% CI, 0.57-0.95; P =.02). Likewise, there were no significant differences between the atorvastatin group and the placebo group in the incidence of secondary outcomes of coronary revascularization procedures, worsening heart failure, or worsening angina, although there were fewer strokes in the atorvastatin group than in the placebo group (12 vs 24 events; P =.045). In the atorvastatin group, mean low-density lipoprotein cholesterol level declined from 124 mg/dL (3.2 mmol/L) to 72 mg/dL (1.9 mmol/L). Abnormal liver transaminases (>3 times upper limit of normal) were more common in the atorvastatin group than in the placebo group (2.5% vs 0.6%; P<.001).\n For patients with acute coronary syndrome, lipid-lowering therapy with atorvastatin, 80 mg/d, reduces recurrent ischemic events in the first 16 weeks, mostly recurrent symptomatic ischemia requiring rehospitalization.",
"Individuals with diabetes are at increased risk of cardiovascular morbidity and mortality, although typically their plasma concentrations of LDL cholesterol are similar to those in the general population. Previous evidence about the effects of lowering cholesterol in people with diabetes has been limited, and most diabetic patients do not currently receive cholesterol-lowering therapy despite their increased risk.\n 5963 UK adults (aged 40-80 years) known to have diabetes, and an additional 14573 with occlusive arterial disease (but no diagnosed diabetes), were randomly allocated to receive 40 mg simvastatin daily or matching placebo. Prespecified analyses in these prior disease subcategories, and other relevant subcategories, were of first major coronary event (ie, non-fatal myocardial infarction or coronary death) and of first major vascular event (ie, major coronary event, stroke or revascularisation). Analyses were also conducted of subsequent vascular events during the scheduled treatment period. Comparisons are of all simvastatin-allocated versus all placebo-allocated participants (ie, intention to treat), which yielded an average difference in LDL cholesterol of 1.0 mmol/L (39 mg/dL) during the 5-year treatment period.\n Both among the participants who presented with diabetes and among those who did not, there were highly significant reductions of about a quarter in the first event rate for major coronary events, for strokes, and for revascularisations. For the first occurrence of any of these major vascular events among participants with diabetes, there was a definite 22% (95% CI 13-30) reduction in the event rate (601 [20.2%] simvastatin-allocated vs 748 [25.1%] placebo-allocated, p<0.0001), which was similar to that among the other high-risk individuals studied. There were also highly significant reductions of 33% (95% CI 17-46, p=0.0003) among the 2912 diabetic participants who did not have any diagnosed occlusive arterial disease at entry, and of 27% (95% CI 13-40, p=0.0007) among the 2426 diabetic participants whose pretreatment LDL cholesterol concentration was below 3.0 mmol/L (116 mg/dL). The proportional reduction in risk was also about a quarter among various other subcategories of diabetic patient studied, including: those with different duration, type, or control of diabetes; those aged over 65 years at entry or with hypertension; and those with total cholesterol below 5.0 mmol/L (193 mg/dL). In addition, among participants who had a first major vascular event following randomisation, allocation to simvastatin reduced the rate of subsequent events during the scheduled treatment period.\n The present study provides direct evidence that cholesterol-lowering therapy is beneficial for people with diabetes even if they do not already have manifest coronary disease or high cholesterol concentrations. Allocation to 40 mg simvastatin daily reduced the rate of first major vascular events by about a quarter in a wide range of diabetic patients studied. After making allowance for non-compliance, actual use of this statin regimen would probably reduce these rates by about a third. For example, among the type of diabetic patient studied without occlusive arterial disease, 5 years of treatment would be expected to prevent about 45 people per 1000 from having at least one major vascular event (and, among these 45 people, to prevent about 70 first or subsequent events during this treatment period). Statin therapy should now be considered routinely for all diabetic patients at sufficiently high risk of major vascular events, irrespective of their initial cholesterol concentrations.",
"Studies have demonstrated that statins administered to individuals with risk factors for coronary heart disease (CHD) reduce CHD events. However, many of these studies were too small to assess all-cause mortality or outcomes in important subgroups.\n To determine whether pravastatin compared with usual care reduces all-cause mortality in older, moderately hypercholesterolemic, hypertensive participants with at least 1 additional CHD risk factor.\n Multicenter (513 primarily community-based North American clinical centers), randomized, nonblinded trial conducted from 1994 through March 2002 in a subset of participants from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).\n Ambulatory persons (n = 10 355), aged 55 years or older, with low-density lipoprotein cholesterol (LDL-C) of 120 to 189 mg/dL (100 to 129 mg/dL if known CHD) and triglycerides lower than 350 mg/dL, were randomized to pravastatin (n = 5170) or to usual care (n = 5185). Baseline mean total cholesterol was 224 mg/dL; LDL-C, 146 mg/dL; high-density lipoprotein cholesterol, 48 mg/dL; and triglycerides, 152 mg/dL. Mean age was 66 years, 49% were women, 38% black and 23% Hispanic, 14% had a history of CHD, and 35% had type 2 diabetes.\n Pravastatin, 40 mg/d, vs usual care.\n The primary outcome was all-cause mortality, with follow-up for up to 8 years. Secondary outcomes included nonfatal myocardial infarction or fatal CHD (CHD events) combined, cause-specific mortality, and cancer.\n Mean follow-up was 4.8 years. During the trial, 32% of usual care participants with and 29% without CHD started taking lipid-lowering drugs. At year 4, total cholesterol levels were reduced by 17% with pravastatin vs 8% with usual care; among the random sample who had LDL-C levels assessed, levels were reduced by 28% with pravastatin vs 11% with usual care. All-cause mortality was similar for the 2 groups (relative risk [RR], 0.99; 95% confidence interval [CI], 0.89-1.11; P =.88), with 6-year mortality rates of 14.9% for pravastatin vs 15.3% with usual care. CHD event rates were not significantly different between the groups (RR, 0.91; 95% CI, 0.79-1.04; P =.16), with 6-year CHD event rates of 9.3% for pravastatin and 10.4% for usual care.\n Pravastatin did not reduce either all-cause mortality or CHD significantly when compared with usual care in older participants with well-controlled hypertension and moderately elevated LDL-C. The results may be due to the modest differential in total cholesterol (9.6%) and LDL-C (16.7%) between pravastatin and usual care compared with prior statin trials supporting cardiovascular disease prevention.",
"Recent clinical trials have demonstrated that aggressive lipid lowering by statins could prevent recurrent events after acute coronary syndrome (ACS). We hypothesized that this efficacy was caused by a significant reduction in plaque volume by aggressive LDL cholesterol (LCL-C) lowering. The present study investigated the effect of early statin treatment on plaque volume of a nonculprit lesion by serial volumetric intravascular ultrasound in patients with ACS.\n Seventy patients with ACS were enrolled. All patients underwent emergency coronary angiography and percutaneous coronary intervention (PCI). They were randomized to intensive lipid-lowering therapy (n=35; atorvastatin 20 mg/d) or control (n=35) groups after PCI. Volumetric intravascular ultrasound analyses were performed at baseline and 6-month follow-up for a non-PCI site in 48 patients (atorvastatin, n=24; control, n=24). LDL-C level was significantly decreased by 41.7% in the atorvastatin group compared with the control group, in which LDL-C was increased by 0.7% (P<0.0001). Plaque volume was significantly reduced in the atorvastatin group (13.1+/-12.8% decrease) compared with the control group (8.7+/-14.9% increase; P<0.0001). Percent change in plaque volume showed a significant positive correlation with follow-up LDL-C level (R=0.456, P=0.0011) and percent LDL-C reduction (R=0.612, P<0.0001), even in patients with baseline LDL-C <125 mg/dL.\n Early aggressive lipid-lowering therapy by atorvastatin for 6 months significantly reduced the plaque volume in patients with ACS. Percent change in plaque volume showed a significant positive correlation with percent LDL-C reduction, even in patients with low baseline LDL-C.",
"Cardiovascular disease (CVD) risk is increased in type 2 diabetes. The purpose of this study was to assess the effect of 10 mg of atorvastatin versus placebo on CVD prevention in subjects with type 2 diabetes and LDL cholesterol levels below contemporary guideline targets.\n Subjects were randomly assigned to receive 10 mg of atorvastatin or placebo in a 4-year, double-blind, parallel-group study. The composite primary end point comprised cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, recanalization, coronary artery bypass surgery, resuscitated cardiac arrest, and worsening or unstable angina requiring hospitalization.\n A total of 2,410 subjects with type 2 diabetes were randomized. Mean LDL cholesterol reduction in the atorvastatin group over 4 years was 29% versus placebo (P < 0.0001). When we compared atorvastatin versus placebo, composite primary end point rates were 13.7 and 15.0%, respectively (hazard ratio 0.90 [95% CI 0.73-1.12]). In the subset of 1,905 subjects without prior myocardial infarction or interventional procedure, 10.4% of atorvastatin- and 10.8% of placebo-treated subjects experienced a primary end point (0.97 [0.74-1.28]). In the 505 subjects with prior myocardial infarction or interventional procedure, 26.2% of atorvastatin- and 30.8% of placebo-treated subjects experienced a primary end point (0.82 [0.59-1.15]). Relative risk reductions in fatal and nonfatal myocardial infarction were 27% overall (P = 0.10) and 19% (P = 0.41) and 36% (P = 0.11) for subjects without and with prior myocardial infarction or interventional procedure, respectively.\n Composite end point reductions were not statistically significant. This result may relate to the overall study design, the types of subjects recruited, the nature of the primary end point, and the protocol changes required because of changing treatment guidelines. For these reasons, the results of the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-Insulin-Dependent Diabetes Mellitus (ASPEN) did not confirm the benefit of therapy but do not detract from the imperative that the majority of diabetic patients are at risk of coronary heart disease and deserve LDL cholesterol lowering to the currently recommended targets.",
"Statins reduce the incidence of strokes among patients at increased risk for cardiovascular disease; whether they reduce the risk of stroke after a recent stroke or transient ischemic attack (TIA) remains to be established.\n We randomly assigned 4731 patients who had had a stroke or TIA within one to six months before study entry, had low-density lipoprotein (LDL) cholesterol levels of 100 to 190 mg per deciliter (2.6 to 4.9 mmol per liter), and had no known coronary heart disease to double-blind treatment with 80 mg of atorvastatin per day or placebo. The primary end point was a first nonfatal or fatal stroke.\n The mean LDL cholesterol level during the trial was 73 mg per deciliter (1.9 mmol per liter) among patients receiving atorvastatin and 129 mg per deciliter (3.3 mmol per liter) among patients receiving placebo. During a median follow-up of 4.9 years, 265 patients (11.2 percent) receiving atorvastatin and 311 patients (13.1 percent) receiving placebo had a fatal or nonfatal stroke (5-year absolute reduction in risk, 2.2 percent; adjusted hazard ratio, 0.84; 95 percent confidence interval, 0.71 to 0.99; P=0.03; unadjusted P=0.05). The atorvastatin group had 218 ischemic strokes and 55 hemorrhagic strokes, whereas the placebo group had 274 ischemic strokes and 33 hemorrhagic strokes. The five-year absolute reduction in the risk of major cardiovascular events was 3.5 percent (hazard ratio, 0.80; 95 percent confidence interval, 0.69 to 0.92; P=0.002). The overall mortality rate was similar, with 216 deaths in the atorvastatin group and 211 deaths in the placebo group (P=0.98), as were the rates of serious adverse events. Elevated liver enzyme values were more common in patients taking atorvastatin.\n In patients with recent stroke or TIA and without known coronary heart disease, 80 mg of atorvastatin per day reduced the overall incidence of strokes and of cardiovascular events, despite a small increase in the incidence of hemorrhagic stroke. (ClinicalTrials.gov number, NCT00147602 [ClinicalTrials.gov].).\n Copyright 2006 Massachusetts Medical Society.",
"Renal transplant recipients are at increased risk of premature cardiovascular disease. Although statins reduce cardiovascular risk in the general population, their efficacy and safety in renal transplant recipients have not been established. We investigated the effects of fluvastatin on cardiac and renal endpoints in this population.\n We did a multicentre, randomised, double-blind, placebo-controlled trial in 2102 renal transplant recipients with total cholesterol 4.0-9.0 mmol/L. We randomly assigned patients fluvastatin (n=1050) or placebo (n=1052) and follow up was for 5-6 years. The primary endpoint was the occurrence of a major adverse cardiac event, defined as cardiac death, non-fatal myocardial infarction (MI), or coronary intervention procedure. Secondary endpoints were individual cardiac events, combined cardiac death or non-fatal MI, cerebrovascular events, non-cardiovascular death, all-cause mortality, and graft loss or doubling of serum creatinine. Analysis was by intention to treat.\n After a mean follow-up of 5.1 years, fluvastatin lowered LDL cholesterol concentrations by 32%. Risk reduction with fluvastatin for the primary endpoint (risk ratio 0.83 [95% CI 0.64-1.06], p=0.139) was not significant, although there were fewer cardiac deaths or non-fatal MI (70 vs 104, 0.65 [0.48-0.88] p=0.005) in the fluvastatin group than in the placebo group. Coronary intervention procedures and other secondary endpoints did not differ significantly between groups.\n Although cardiac deaths and non-fatal MI seemed to be reduced, fluvastatin did not generally reduce rates of coronary intervention procedures or mortality. Overall effects of fluvastatin were similar to those of statins in other populations.",
"A double-blind randomised placebo-controlled trial of antihypertensive treatment was conducted in patients over the age of 60. Entry criteria included both a sitting diastolic blood pressure on placebo treatment in the range 90-119 mm Hg and a systolic pressure in the range 160-239 mm Hg. 840 patients were randomised either to active treatment (hydrochlorothiazide + triamterene) or to matching placebo. If the blood pressure remained raised, methyldopa was added to the active regimen and matching placebo in the placebo group. An overall intention-to-treat analysis, combining the double-blind part of the trial and all subsequent follow-up, revealed a non-significant change in total mortality rate (-9%, p = 0.41) but a significant reduction in cardiovascular mortality rate (-27%, p = 0.037). The latter was due to a reduction in cardiac mortality (-38%, p = 0.036) and a non-significant decrease in cerebrovascular mortality (-32%, p = 0.16). In the double-blind part of the trial, total mortality rate was not significantly reduced (-26%, p = 0.077). Cardiovascular mortality was reduced in the actively treated group (-38%, p = 0.023), owing to a reduction in cardiac deaths (-47%, p = 0.048) and a non-significant decrease in cerebrovascular mortality (-43%, p = 0.15). Deaths from myocardial infarction were reduced (-60%, p = 0.043). Study-terminating morbid cardiovascular events were significantly reduced by active treatment (-60%, p = 0.0064). Non-terminating cerebrovascular events were reduced (-52%, p = 0.026), but the non-terminating cardiac events were not (+3%, p = 0.98). In the patients randomised to active treatment there were 29 fewer cardiovascular events and 14 fewer cardiovascular deaths per 1000 patient years during the double-blind part of the trial.",
"Drug therapy for hypercholesterolaemia has remained controversial mainly because of insufficient clinical trial evidence for improved survival. The present trial was designed to evaluate the effect of cholesterol lowering with simvastatin on mortality and morbidity in patients with coronary heart disease (CHD). 4444 patients with angina pectoris or previous myocardial infarction and serum cholesterol 5.5-8.0 mmol/L on a lipid-lowering diet were randomised to double-blind treatment with simvastatin or placebo. Over the 5.4 years median follow-up period, simvastatin produced mean changes in total cholesterol, low-density-lipoprotein cholesterol, and high-density-lipoprotein cholesterol of -25%, -35%, and +8%, respectively, with few adverse effects. 256 patients (12%) in the placebo group died, compared with 182 (8%) in the simvastatin group. The relative risk of death in the simvastatin group was 0.70 (95% CI 0.58-0.85, p = 0.0003). The 6-year probabilities of survival in the placebo and simvastatin groups were 87.6% and 91.3%, respectively. There were 189 coronary deaths in the placebo group and 111 in the simvastatin group (relative risk 0.58, 95% CI 0.46-0.73), while noncardiovascular causes accounted for 49 and 46 deaths, respectively. 622 patients (28%) in the placebo group and 431 (19%) in the simvastatin group had one or more major coronary events. The relative risk was 0.66 (95% CI 0.59-0.75, p < 0.00001), and the respective probabilities of escaping such events were 70.5% and 79.6%. This risk was also significantly reduced in subgroups consisting of women and patients of both sexes aged 60 or more. Other benefits of treatment included a 37% reduction (p < 0.00001) in the risk of undergoing myocardial revascularisation procedures. This study shows that long-term treatment with simvastatin is safe and improves survival in CHD patients.",
"Cardiovascular disease (CVD) is the most important cause of mortality in patients with type 2 diabetes. We aimed to determine the effect of statin therapy versus placebo on the progression of carotid intima-media thickness (IMT) in type 2 diabetic patients without manifest CVD.\n A randomized, placebo-controlled, double-blind clinical trial was performed in 250 patients with type 2 diabetes. Patients were given either 0.4 mg cerivastatin or placebo daily. In August 2001, when cerivastatin was withdrawn from the market, 0.4 mg cerivastatin was replaced by 20 mg simvastatin without deblinding the study. The primary end point was the change of mean common carotid IMT, as measured by B-mode ultrasound, over 2 years.\n Common carotid IMT at baseline was 0.780 mm in the placebo group and 0.763 mm in the statin group and did not change significantly after 2 years. There was no significant difference in IMT change in any carotid segment between the groups. LDL cholesterol was reduced by 25% in the statin group and increased by 8% in the placebo group (P <0.001). Cardiovascular events occurred in 12 patients in the placebo group and two patients in the statin group (P=0.006).\n There was no effect of 2 years' statin therapy on carotid IMT in type 2 diabetic subjects. The natural history of IMT in our patients was milder than anticipated. In contrast, we observed a significantly lower cardiovascular event rate on statin therapy. Prognostic tools other than IMT should be explored in this patient group."
] |
Reductions in all-cause mortality, major vascular events and revascularisations were found with no excess of adverse events among people without evidence of CVD treated with statins.
|
CD007912
|
[
"15940775",
"11409662",
"17443749",
"10955337"
] |
[
"The effects of an exercise program for older adults with osteoarthritis of the hip.",
"Primary care-based physical activity programs: effectiveness in sedentary older patients with osteoarthritis symptoms.",
"Physical activity for osteoarthritis management: a randomized controlled clinical trial evaluating hydrotherapy or Tai Chi classes.",
"The effects of a health educational and exercise program for older adults with osteoarthritis for the hip or knee."
] |
[
". Evaluation of an 8-week exercise program with strength training and lifestyle advice for older adults with osteoarthritis (OA) of the hip. Outcome measures were pain, hip function, disability, quality of life (QOL), and body mass index (BMI).\n Inclusion criteria for this randomized controlled trial were: age >or=55 years, clinical diagnosis of OA according to American College of Rheumatology criteria, and living independently. Interview and physical data were collected at baseline, post-test, and followup (3 mo) by trained interviewers and physical therapists with validated instruments: Harris Hip Score, Sickness Impact Profile, Groningen Activity Restriction Scale, functional tests (walking, timed Up & Go, ascending and descending stairs, and toe reaching), and visual analog scales (pain and QOL). Data were analyzed on an intention-to-treat basis. Effect sizes were calculated.\n There were 109 participants (55 experimental, 54 controls). The 15 participants who dropped out were characterized by less tolerance to pain and younger age. The program had a positive effect on pain (moderate effect at post-test and small effect at followup), hip function (small effect at post-test), self-reported disability (small effect at followup), and the timed Up & Go test (small effect at followup). It did not affect QOL, other measures of observed disability, or BMI.\n The exercise program had positive effects on pain and hip function, which are important mediators of disability. This study fulfilled a need for older adults with hip OA and provides evidence of the benefit of exercise in the management of hip OA.",
"This study examined, in a group of older patients, (a) the effectiveness of an invitation to participate in a program providing individualized physical activity advice in a primary care setting and (b) the changes in self-reported physical activity and symptoms in patients with osteoarthritis (OA).\n Healthy, sedentary community-dwelling men and women aged 60 years or more were invited to participate. Following random allocation, the intervention group received individualized physical activity advice at baseline and at 3, 6, and 12 months followup.\n Of the 299 people who satisfied the study's inclusion criteria, a subgroup of 69 people reported pain and stiffness of the hip or knee at baseline. These patients reported increases in frequency and time of walking and vigorous exercise (all P < 0.001), with no change to OA symptom scores (pain and stiffness), and a small decline in physical functioning was reported at 12 months followup in the control group only (P = 0.027). At the 12-month followup more intervention participants than control participants (P = 0.013) reported a greater intention to exercise.\n An offer of primary care-based physical activity advice, with an emphasis on the benefits for general health (rather than \"treatment\" for OA), will attract individuals with OA symptoms. Although the present study was unable to demonstrate intervention-control group differences for the majority of outcomes, intention to exercise did appear to be positively influenced.",
"To determine whether Tai Chi or hydrotherapy classes for individuals with chronic symptomatic hip or knee osteoarthritis (OA) result in measurable clinical benefits.\n A randomized controlled trial was conducted among 152 older persons with chronic symptomatic hip or knee OA. Participants were randomly allocated for 12 weeks to hydrotherapy classes (n = 55), Tai Chi classes (n = 56), or a waiting list control group (n = 41). Outcomes were assessed 12 and 24 weeks after randomization and included pain and physical function (Western Ontario and McMaster Universities Osteoarthritis Index), general health status (Medical Outcomes Study Short Form 12 Health Survey [SF-12], version 2), psychological well-being, and physical performance (Up and Go test, 50-foot walk time, timed stair climb).\n At 12 weeks, compared with controls, participants allocated to hydrotherapy classes demonstrated mean improvements (95% confidence interval) of 6.5 (0.4, 12.7) and 10.5 (3.6, 14.5) for pain and physical function scores (range 0-100), respectively, whereas participants allocated to Tai Chi classes demonstrated improvements of 5.2 (-0.8, 11.1) and 9.7 (2.8, 16.7), respectively. Both class allocations achieved significant improvements in the SF-12 physical component summary score, but only allocation to hydrotherapy achieved significant improvements in the physical performance measures. All significant improvements were sustained at 24 weeks. In this almost exclusively white sample, class attendance was higher for hydrotherapy, with 81% attending at least half of the available 24 classes, compared with 61% for Tai Chi.\n Access to either hydrotherapy or Tai Chi classes can provide large and sustained improvements in physical function for many older, sedentary individuals with chronic hip or knee OA.",
"Evaluation of a self-management program for patients with osteoarthritis (OA) of the hip or knee. The program, which consisted of 6 weekly sessions of 2 hours, included health education by a peer and physical exercises taught by a physical therapist.\n Randomized controlled trial. Inclusion criteria were diagnosis of OA of the hip or knee according to ACR clinical and radiographic criteria and age 55 to 75 years. Exclusion criteria: on waiting list for joint replacement. There were pretest, posttest, and followup (6 months) assessments. The experimental group consisted of 56 patients, the control group 49. Outcome variables were pain, quality of life, activity restrictions, knowledge about OA, self-efficacy, body mass index (BMI), and mobility measures. Attention was also paid to effects on health care utilization and lifestyle behavior.\n Significant MANOVA group x time effects (p < 0.05, one-sided) were found for pain, quality of life, strength of the left M. quadriceps, knowledge, self-efficacy, BMI, physically active lifestyle, and visits to the physical therapist. Most effects were moderate at posttest assessment and smaller at followup. No effects were found for range of motion and functional tasks.\n The program was reasonably effective, but more attention should be paid to proactive followup interventions and to the selection of participants."
] |
The limited number and small sample size of the included RCTs restricts the confidence that can be attributed to these results. Adequately powered RCTs evaluating exercise programs specifically designed for people with symptomatic hip OA need to be conducted.
|
CD008948
|
[
"21187618",
"14977302",
"20102063",
"19893466",
"17262145",
"14600693",
"16674744",
"19840635",
"6955420",
"9545899",
"16856902"
] |
[
"Comparison of 2% chlorhexidine and 5.25% sodium hypochlorite irrigating solutions on postoperative pain: a randomized clinical trial.",
"Antibacterial activity of 2% chlorhexidine gluconate and 5.25% sodium hypochlorite in infected root canal: in vivo study.",
"Antimicrobial effect of 0.2% chlorhexidine in infected root canals.",
"Effect of sodium hypochlorite with the addition of a proteolytic enzyme on postoperative discomfort: a multicenter randomized clinical trial.",
"Influence of sodium hypochlorite-based irrigants on the susceptibility of intracanal microbiota to biomechanical preparation.",
"The effect of chlorhexidine as an endodontic disinfectant.",
"In vivo evaluation of microbial reduction after chemo-mechanical preparation of human root canals containing necrotic pulp tissue.",
"Antibacterial efficacy of MTAD final rinse and two percent chlorhexidine gel medication in teeth with apical periodontitis: a randomized double-blinded clinical trial.",
"In vivo evaluation of chlorhexidine gluconate solution and sodium hypochlorite solution as root canal irrigants.",
"Effects of subgingival chlorhexidine irrigation on peri-implant maintenance.",
"Benefit of \"one-stage full-mouth disinfection\" is explained by disinfection and root planing within 24 hours: a randomized controlled trial."
] |
[
"To compare the levels of postoperative pain after cleaning and shaping of root canals using two different root canal irrigants for debridement.\n Forty patients with irreversible pulpitis, pulp necrosis and non-vital teeth exhibiting acute apical periodontitis requiring root canal treatment were included. At random, canals were cleaned and shaped with the following protocols. 2% chlorhexidine solution in group I and 5.25% sodium hypochlorite solution in group II were used as an irrigants. Access cavities were closed with a sterile cotton pellet and cavit. The patients recorded degree of pain at various time intervals after cleaning and shaping on a visual analogue scale for 1 week.\n The mean pain score for group I was between 0.65 and 3.35 and for group II was between 0.95 and 4.50. There was significant difference in the pain level between the two groups only at 6 th hour postoperatively (P<0.05) and the pain was more in sodium hypochlorite group.\n More pain was present in teeth irrigated using 5.25% sodium hypochlorite when compared to that in teeth irrigated using 2% chlorhexidine solution. Significant difference in pain level was present only at 6th hour postoperatively, and at all other periods (24 th hour, 4 th and 7 th days) there was no significant difference in pain level between the two groups.",
"In this study, the antibacterial activity of the different antibacterial solutions using as root canal irrigant was compared in the teeth with pulpal necrosis and with periapical pathosis. Thirty root canals of incisors and premolars of 20 patients were used. Before and after the root canal preparation, two canal samples were obtained by a harvesting method using a sterile paper point in the first appointment. During the biomechanical preparation, both irrigant solutions were used for each tooth which were randomly divided into two groups. Last samples were also obtained before the root filling procedure. Samples obtained from the root canals were subjected to microbiologic processing, including anaerobic incubation on trypticase soy agar for 5 to 7 days. After counting of CFU on the plates, we concluded that both chlorhexidine gluconate and sodium hypochlorite were significantly effective to reduce the microorganisms in the teeth with necrotic pulp, periapical pathologies, or both, and could be used successfully as an irrigant solution.",
"The aim of this study was to identify bacteria from the infected root canals of teeth with chronic apical periodontitis, and to evaluate the antibacterial effect of 0.2% chlorhexidine (CHX), as an irrigant, in reducing the microbial flora 48h after root canal preparation. A total of 44 subjects were randomly divided in the experimental group and the control group. The first bacterial samples from all root canals were obtained in the beginning, before any treatment. During mechanical instrumentation, root canals were irrigated three times, with 0.2% CHX in the experimental group, and with saline solution in the control group. All canals were dried and temporarily sealed with zinc oxide-sulfate cement. After 48 h the second samples were obtained. Bacterial samples were subjected to microbiologic processing. The study indicates that 0.2% CHX is significantly effective in reducing the microbial flora, and could be used as an irrigant solution.",
"The purpose of this study was to compare the patient's postoperative discomfort when root canal irrigation was performed either with standard sodium hypochlorite or with sodium hypochlorite with the adjunct of a proteolytic enzyme.\n Two hundred patients were endodontically treated in two clinics. The type of irrigant to be used during root canal instrumentation was randomly assigned. Final irrigation was done using EDTA 17%. The canals were filled by warm vertical condensation with guttha-percha and the coronal seal was made using IRM. Patients were given a questionnaire to assess pain and swelling and the number of analgesics and other drugs taken during the first week after treatment.\n A total of 166 questionnaires could have been evaluated. No significant difference was found between groups for pain, swelling and analgesics taken. Moderate pain and swelling was reported only in the first two days after treatment. No antibiotics use was reported. No guttha-percha excess beyond root apex was found by radiographic assessment.\n The irrigating solution containing a proteolytic enzyme does not produce greater postoperative discomfort as compared to the conventional sodium hypochlorite in patients undergoing endodontic therapy.",
"This study evaluated the microbiological conditions of root canals, using smears and culture from anterior teeth and premolars with necrotic pulps associated with chronic periapical pathologies, before and after biomechanical preparation (BMP). During double-flared instrumentation, 1, 2.5 and 5% sodium hypochlorite (NaOCl)-based irrigants were used in 3 groups: GI (n=39), GII (n=36) and GIII (n=36), respectively. Before BMP, all cultures were positive and the smears showed microbiologically diverse morphotypes, including fusiforms, pleomorphic, rods, cocci and filaments. Quantitatively, 20, 20 and 23 morphotypes were identified in GI, GII and GIII, respectively). After BMP, the percentages of negative cultures in GI, GII and GIII were 74.2%, 86.3% and 93.4% (p>0.05) and the number of morphotypes decreased to 14, 15 and 5, respectively. All teeth with 2 root canals and/or associated fistulas were microbiologically negative after BMP, regardless of irrigant concentration. Gram-negative morphotypes were more susceptible to the action of irrigants. After irrigation with 5% NaOCl, only structural arrangements consisting of Gram-positive cocci and bacilli persisted. Thus, BMP plus 5% NaOCl offered the best antiseptic potential because in the few positive cultures a significant reduction in the number of microbiological morphotypes was also shown (p<0.05).",
"The purpose of this study was to establish whether addition of a 2% chlorhexidine rinse to a conventional treatment protocol enhances the rate of the successful disinfection of the root canal system in vivo.\n Twenty-four teeth with infected necrotic pulps and resorbing apical periodontitis were treated with a conventional technique in which 1% NaOCl as irrigant was used. Half of the cases received an additional rinse with 2% chlorhexidine. Prereduced thioglycollate medium was used to take cultures that were incubated for 4 weeks.\n Cultivable bacteria were retrieved at the conclusion of the first visit in 1 out of 12 chlorhexidine cases whereas in the control group 7 out of 12 cases showed growth. This difference was significant (P < .05).\n The findings are clinically important.",
"To determine in vivo, the degree of microbial reduction after chemo-mechanical preparation of human root canals containing necrotic pulp tissue when using two endodontic irrigating reagents, sodium hypochlorite (NaOCl) or chlorhexidine gel (CHX).\n Thirty-two single rooted teeth with necrotic pulp were divided into two groups. One group (n=16) was irrigated with 2.5% NaOCl, whilst the other group (n=16) was irrigated with 2% CHX gel. Assessment of the bacterial load was accomplished by use of real-time quantitative-polymerase chain reaction (RTQ-PCR) directed against the small subunit ribosomal DNA using the SYBRGreen and TaqMan formats. Statistical analysis was performed using the Mann-Whitney test. For contrast, bacterial load was also determined by traditional culture techniques.\n The bacterial load was reduced substantially in both groups (over 96%). However, using RTQ-PCR the bacterial load before and after chemo-mechanical preparation was greater when compared with evaluation using colony forming units (CFU). Furthermore, as measured by RTQ-PCR, the bacterial reduction in the NaOCl-group (SYBRGreen 99.99%; TaqMan: 99.63%) was significantly greater (P<0.01) than in the CHX-group (SYBRGreen 96.62%; TaqMan: 96.60%). According to culture technique 75% of cases were free of bacteria after chemo-mechanical preparation in the NaOCl-group, whilst 50% of cases were bacteria free in the CHX-group.\n NaOCl has not only a higher capacity to kill microorganisms but is also more able to remove cells from the root canal.",
"Clinical assessment of the efficacy of novel root canal disinfection protocols is an important focus in endodontic research. This randomized double-blinded study assessed the antibacterial efficacy of a final rinse with BioPure MTAD (MTAD) and intracanal medication with 2% chlorhexidine gel (CHX) in teeth with apical periodontitis.\n Canals in 30 teeth (single-rooted and multi-rooted) were prepared by using 1.3% NaOCl, rinsed with MTAD or saline in random sequence, medicated with CHX for 7 days, irrigated with 1.3% NaOCl, and filled. Bacteriologic root canal samples were obtained by aspiration before (1A) and after (1B) canal preparation, after the final rinse (1C), after CHX was flushed (2A), and after final irrigation (2B). Bacteria were enumerated by epifluorescence-microscopy (EFM) by using 2 staining methods and by colony-forming-unit (CFU) counts after 14 days of incubation.\n Bacterial counts (EFM) in 1B were greater than 95% decreased from 1A. Low bacterial densities in 1B, 1C, 2A, and 2B did not differ significantly from each other. EFM counts were consistently higher than CFU counts.\n The final rinse with MTAD and medication with CHX did not reduce bacterial counts beyond levels achieved by canal preparation with NaOCl.",
"nan",
"To evaluate the effect of irrigation with 0.06% chlorhexidine (PerioGard) (CHX) using a powered oral irrigator (Water Pik) with a special subgingival irrigating tip (Pik Pocket Subgingival Tip) compared to rinsing with 0.12% chlorhexidine gluconate once daily.\n Following a prophylaxis, patients were randomly assigned to an irrigation or a rinse group. The following clinical parameters were measured at baseline and at the 3-month end of the study: Modified Gingival Index (MGI), Plaque Index (PI), Bleeding Index (BI), and Calculus Index (CI). Also, a Stain Index (SI) was measured at 3 months.\n Patients irrigating with diluted CHX showed a statistically significant reduction (P < 0.05) from their baseline in the MGI, PI, BI, and CI scores at 3 months. In the rinse group both MGI and BI showed statistically significant reduction from their baseline (P < 0.05) at 3 months. The rinse group showed a nonsignificant (P > 0.05) increase from baseline in CI and a nonsignificant decrease in PI. Intergroup comparisons showed that CHX irrigation produced statistically significantly greater reductions than CHX rinsing in the PI, MGI, and SI. The irrigation group also showed a greater reduction in BI and CI than the rinsing group but these differences were not statistically significant (P = 0.12). The results of this study suggest that use of diluted 0.06% CHX when used in a powered irrigator may be a valuable adjunct to oral health in patients with implants.",
"The beneficial effects of the one-stage, full-mouth disinfection remain controversial in the scientific literature. This might be due to the fact that an entire mouth disinfection with the use of antiseptics has been confused with a full-mouth scaling and root planing. This parallel, single blind RCT study aimed to compare several full-mouth treatment strategies with each other.\n Seventy-one patients with moderate periodontitis were randomly allocated to one of the following treatment strategies: scaling and root planing, quadrant by quadrant, at two-week intervals (negative control, NC), full-mouth scaling and root planing within 2 consecutive days (FRP), or three one-stage, full-mouth disinfection (FM) protocols within 2 consecutive days applying antiseptics to all intra-oral niches for periopathogens using as antiseptics: chlorhexidine (FMCHX) for 2 months, amine fluoride/stannous fluoride for 2 months (FMF), or chlorhexidine for 2 months followed by amine fluoride/stannous fluoride for another 6 months (FMCHX+F). At baseline and after 2, 4, and 8 a series of periodontal parameters were recorded.\n All treatment strategies resulted in significant (p<0.05) improvements of all clinical parameters over the entire duration of the study. Inter-treatment differences were often encountered. The NC group nearly always showed significant smaller improvements than the two CHX groups. The differences between the FRP or FM groups, and the two CHX groups only sporadically reached a statistical significance.\n These observations indicate that the benefits of the \"OSFMD\" protocol are partially due to the use of the antiseptics and partially to the completion of the therapy in a short time."
] |
Although root canal irrigants such as sodium hypochlorite and chlorhexidine appear to be effective at reducing bacterial cultures when compared to saline, most of the studies included in this review failed to adequately report these clinically important and potentially patient-relevant outcomes. There is currently insufficient reliable evidence showing the superiority of any one individual irrigant. The strength and reliability of the supporting evidence was variable and clinicians should be aware that changes in bacterial counts or pain in the early postoperative period may not be accurate indicators of long-term success. Future trials should report both clinician-relevant and patient-preferred outcomes at clearly defined perioperative, as well as long-term, time points.
|
CD002935
|
[
"10924977",
"15770205",
"11747326",
"10630160",
"15860852",
"7836078",
"9231675",
"9273183",
"2839443",
"8226143",
"8581393",
"2169587",
"9132823",
"7605662",
"2067127",
"8777169",
"8830811",
"8117604",
"9060525",
"10863061",
"10598923",
"9294465"
] |
[
"A palliative accelerated irradiation regimen for advanced non-small-cell lung cancer vs. conventionally fractionated 60 GY: results of a randomized equivalence study.",
"A prospective, randomised study to compare two palliative radiotherapy schedules for non-small-cell lung cancer (NSCLC).",
"Evaluation of nurse-led follow up for patients undergoing pelvic radiotherapy.",
"[Radiotherapy for stage III, inoperable, asymptomatic small cell lung cancer. Final results of a prospective randomized study (240 patients)].",
"Results of the Dutch National study of the palliative effect of irradiation using two different treatment schemes for non-small-cell lung cancer.",
"Radical radiotherapy for early nonsmall cell lung cancer.",
"Hyperfractionated radiotherapy alone for clinical stage I nonsmall cell lung cancer.",
"[Radiotherapy in locoregional treatment of inoperable non-small cell lung cancer: results from a series of 381 patients].",
"Results of radical radiation therapy in clinical stage I, technically operable non-small cell lung cancer.",
"Radiation therapy alone for stage I non-small cell lung cancer.",
"Palliative radiation for stage 3 non-small cell lung cancer--a prospective study of two moderately high dose regimens.",
"A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small-cell lung cancer.",
"Radical radiotherapy for medically inoperable non-small cell lung cancer in clinical stage I: a retrospective analysis of 149 patients.",
"Radiotherapy alone for non-small cell lung carcinoma. Five-year disease-free survival and patterns of failure.",
"Radiotherapy in inoperable stage I lung cancer.",
"A randomized study of high-dose split course radiotherapy preceded by high-dose chemotherapy versus high-dose radiotherapy only in locally advanced non-small-cell lung cancer. An EORTC Lung Cancer Cooperative Group trial.",
"High-dose radiation therapy for inoperable non-small cell lung cancer without mediastinal involvement (clinical stage N0, N1).",
"Induction chemotherapy plus high-dose radiotherapy versus radiotherapy alone in locally advanced unresectable non-small-cell lung cancer.",
"Initial versus delayed accelerated hyperfractionated radiation therapy and concurrent chemotherapy in limited small-cell lung cancer: a randomized study.",
"A study of postoperative radiotherapy in patients with non-small-cell lung cancer: a randomized trial.",
"Limited field irradiation for medically inoperable patients with peripheral stage I non-small cell lung cancer.",
"Randomized study of initial versus late chest irradiation combined with chemotherapy in limited-stage small-cell lung cancer. Aarhus Lung Cancer Group."
] |
[
"Radiation oncologists are often faced with patients with advanced non-small-cell lung cancer (NSCLC), who are not suitable candidates for state-of-the-art radical treatment, but who also are not judged to have a very short life expectancy. Some physicians treat these patients palliatively, whereas others advocate more intensive treatment. To find out if there is a substantial difference in outcome between these approaches, we performed a randomized prospective study.\n Between 1994 and 1998, 152 eligible patients with advanced NSCLC Stage III (n = 121) or minimal Stage IV (n = 31) were randomized to receive conventionally fractionated (cf; A: 60 Gy, 6 weeks, n = 79) or short-term treatment (PAIR; B: 32 Gy, 2 Gy b.i.d.; n = 73) of tumor and mediastinum.\n One-year survival rate for all patients was 37% with no significant difference between the two treatment arms (A: 36%; B: 38%; p = 0.76). As far as can be judged from limited data available, palliation was adequate and similar for the two treatment arms. Apart from expected differences in the time course of esophagitis, acute side effects were moderate and equally distributed. No severe late effects were observed.\n In the present randomized trial, survival and available data on palliation were not different after cf to 60 Gy compared to the palliative PAIR regimen. Therefore, for patients who are not suitable for radical treatment approaches, the prescription of a palliative short-term irradiation appears preferable compared to cf over several weeks.",
"A prospective randomised study compared two palliative radiotherapy schedules for inoperable symptomatic non-small-cell lung cancer (NSCLC). After stratification, 100 patients were randomly assigned to 20 Gy/5 fractions (fr)/5 days (arm A) or 16 Gy/2 fr/day 1 and 8 (arm B). There were 90 men and 10 women aged 47-81 years (mean 66), performance status 1-4 (median 2). The major clinical characteristics and incidence and degree of initial disease-related symptoms were similar in both groups. Treatment effects were assessed using patient's chart, doctor's scoring of symptomatic change and chest X-ray. Study end points included degree and duration of symptomatic relief, treatment side effects, objective response rates and overall survival. A total of 55 patients were assigned to arm A and 45 to arm B. In all, 98 patients received assigned treatment, whereas two patients died before its termination. Treatment tolerance was good and did not differ between study arms. No significant differences between study arms were observed in the degree of relief of all analysed symptoms. Overall survival time differed significantly in favour of arm B (median 8.0 vs 5.3 months; P=0.016). Both irradiation schedules provided comparable, effective palliation of tumour-related symptoms. The improved overall survival and treatment convenience of 2-fraction schedule suggest its usefulness in the routine management of symptomatic inoperable NSCLC.",
"This study reports results from a randomised controlled trial of nurse-led care and was designed to determine whether nurse-led follow up improved patients morbidity and satisfaction with care in men treated with radical radiotherapy for prostate and bladder cancer. The aim was to compare outcomes in terms of toxicity, symptoms experienced, quality of life, satisfaction with care and health care costs, between those receiving nurse-led care and a group receiving standard care. The study population was of men prescribed radical radiotherapy (greater than 60 Gy). Participants completed self-assessment questionnaires for symptoms and quality of life within the first week of radiotherapy treatment, at week 3, 6 and 12 weeks from start of radiotherapy. Satisfaction with clinical care was also assessed at 12 weeks post-treatment. Observer-rated RTOG toxicity scores were recorded pre-treatment, weeks 1, 3, 6 and 12 weeks from start of radiotherapy. The results presented in this paper are on 115 of 132 (87%) of eligible men who agreed to enter the randomised trial. 6 men (4%) refused and 11 (8%) were missed for inclusion in the study. Data were analysed as a comparison at cross-sectional time points and as a general linear model using multiple regression. There was no significant difference in maximum symptom scores over the time of the trial between nurse-led follow-up care and conventional medical care. Differences were seen in scores in the initial self assessment of symptoms (week 1) that may have been as a result of early nursing intervention. Those men who had received nurse-led care were significantly more satisfied (P < 0.002) at 12 weeks and valued the continuity of the service provided. There were also significant (P < 0.001) cost benefits, with a 31% reduction in costs with nurse-led, compared to medically led care. Evidence from this study suggests that a specialist nurse is able to provide safe follow up for men undergoing radiotherapy. The intervention focused on coping with symptoms, and provided continuity of care and telephone support. Further work is required to improve the management of patients during and after radiotherapy.",
"To report the results of a prospective randomized study concerning the role of radiotherapy in the treatment of stage III, unresectable, asymptomatic non-small cell lung cancer.\n Between 1992 and 1996, 240 patients with stage III, unresectable, asymptomatic non-small cell lung cancer were enrolled in this study, and sequentially randomized to one of the three treatment arms: conventional irradiation, hypofractionated irradiation and control group. In the conventional irradiation arm (79 patients), a dose of 50 Gy in 25 fractions in five weeks was delivered to the primary tumor and the mediastinum. In the hypofractionated irradiation arm (81 patients), there were two courses of irradiation separated by an interval of four weeks. In each series, patients received 20 Gy in five fractions in five days, in the same treatment volume as the conventional irradiation group. In the control group arm, 80 patients initially did not receive radiotherapy and were only observed. Delayed palliative hypofractionated irradiation (20-25 Gy in four to five fractions in four to five days) was given to the primary tumor when major symptoms developed.\n The two-year actuarial survival rates for patients in the conventional irradiation, hypofractionated irradiation and control group arms were 18%, 6% and 0%, with a median survival time of 12 months, nine months and six months respectively. The differences between survival rates were statistically significant at the 0.05 level.\n Although irradiation provides good palliation, the results are disappointing. The comparison of conventional and hypofractionated irradiation shows an advantage for conventional schedules.",
"A national multicenter randomized study compared the efficacy of 2 x 8 Gy versus our standard 10 x 3 Gy in patients with inoperable stage IIIA/B (with an Eastern Cooperative Oncology Group score of 3 to 4 and/or substantial weight loss) and stage IV non-small-cell lung cancer.\n Between January 1999 and June 2002, 297 patients were eligible and randomized to receive either 10 x 3 Gy or 2 x 8 Gy by external-beam irradiation. The primary end point was a patient-assessed score of treatment effect on seven thoracic symptoms using an adapted Rotterdam Symptom Checklist. Study sample size was determined based on an average total symptom score difference of more than one point over the initial 39 weeks post-treatment. The time course of symptom scores were also evaluated, and other secondary end points were toxicity and survival.\n Both treatment arms were equally effective, as the average total symptom score over the initial 39 weeks did not differ. However, the pattern in time of these scores differed significantly (P < .001). Palliation in the 10 x 3-Gy arm was more prolonged (until week 22) with less worsening symptoms than in 2 x 8-Gy. Survival in the 10 x 3-Gy arm was significantly (P = .03) better than in the 2 x 8-Gy arm with 1-year survival of 19.6% (95%CI, 14.1% to 27.3%) v 10.9% (95%CI, 6.9% to 17.3%).\n The 10 x 3-Gy radiotherapy schedule is preferred over the 2 x 8-Gy schedule for palliative treatment, as it improves survival and results in a longer duration of the palliative response.",
"To evaluate the results of a departmental treatment policy in a consecutive series of patients with nonsmall cell carcinoma of the lung. A second purpose was to estimate the survival of patients treated with radical intent. A third purpose was to estimate the impact of comorbidity on the selection of patients for treatment and on its outcome.\n The records of 720 consecutive patients referred to a single Department of Radiation Oncology between 1979 and 1985 were reviewed. One hundred fifty patients with early stage (Stage I and II disease) were studied in detail and the results are presented for the outcome of 103 patients treated by radical radiotherapy. All patients were followed for a minimum period of five years or until death.\n Patients referred for radiation therapy were elderly and usually had squamous cell carcinoma of the lung. Comorbidity was significant as was weight loss which occurred in a third of patients. The overall survival of patients treated with radical intent was 13%. In a small subgroup of patients with T1 tumors without weight loss and aged under 70 survival reached 50% at 5 years with no treatment-related mortality and with insignificant treatment-related morbidity.\n Highly selected subsets of patients suitable for treatment with radiotherapy can be defined equally as well as highly selected subsets of patients can be selected for surgery. Treatment outcome can be surprisingly good in these subsets indicating that the treatment of nonsmall cell lung cancer, particularly in older patients without comorbidity should not automatically be by a surgical approach.",
"Among patients with Stage I nonsmall cell lung cancer (NSCLC), those treated with conventional radiotherapy show poorer prognosis than those treated by surgery. To improve the prognosis of such patients, we have used hyperfractionated radiation therapy.\n Between 1988 and 1993, 49 patients were treated with hyperfractionated radiotherapy with 1.2 Gy twice daily to a total dose of 69.6 Gy. All patients were technically operable, but 29 had medical problems and 20 refused surgery. The median age and Karnofsky Performance Status was 63 years and 90, respectively. No patient received chemotherapy or immunotherapy. Prophylactic mediastinal irradiation was not given.\n The median survival time was 33 months, and the 5-year survival rate was 30%. The rate at 5 years for freedom from each of relapse, local recurrence, mediastinal lymphnode metastasis, and distant metastasis was 41%, 55%, 89%, and 75%, respectively. Univariate analysis revealed that higher Karnofsky Performance Status score, absence of weight loss before treatment, and T1 stage were associated with better survival, although the T stage became insignificant on multivariate analysis. There were two Grade 3 acute toxicities and three Grade 3 late toxicities, but there was no Grade 4-5 toxicity.\n The results of this study compare favorably with those of most previous studies employing conventional fractionation. Further studies on hyperfractionation seem to be warranted for Stage I NSCLC.",
"The prognosis of inoperable non-small cell lung cancer (NSCLC) is poor and thoracic radiation therapy is usually the main step of the therapeutic approach. The results of a retrospective analysis of a series of 381 patients treated from 1977 to 1990 for an inoperable NSCLC are reported.\n Three hundred and twenty two men and 59 women were included into the study. Their mean age was 66 years. A squamous cell carcinoma was observed in 276 cases (72%). A superior vena cava syndrome or a Pancoast's syndrome were present in 21 and 26 patients, respectively. Fifty-two per cent of the patients had a WHO performance status > or = 2. According to the TNM classification, the tumor distribution was as follows: 11 T1, 153 T2, 175 T3, and 42 T4. The mediastinum was involved in 174 patients. All patients were treated by external radiation therapy with a total dose of 60-65 Gy. Classical fractionation of the irradiation dose was done in 217 patients and hypofractionation was used for 164 patients.\n After treatment, improvement of the superior vena and Pancoast's syndromes was observed in 90% of the patients. Radiological complete response was obtained in 177 patients (47%). The 5-year overall survival rate was 6.2%. No significant differences in survival according to the initial tumor size, the mediastinum status or the fractionation scheme were noted. The 5-year survival rate was 13% in patients with a tumor that completely responded to irradiation. Death was mainly due to local failure (231 patients, 69%) and metastatic disease (107 patients, 32%). The radiotherapy tolerance was acceptable.\n Although irradiation provides good palliation and a 10%-survival rate at 3 years, the results relating to radiation therapy were disappointing.",
"From 1970 to 1983, 1,646 lung cancer patients were referred for treatment to the Hunter Radiation Therapy Center, Yale-New Haven Hospital. Forty-three patients had clinical Stage I non-small cell lung cancer felt to be surgically resectable but were treated with radical radiation therapy either for medical reasons (37 patients) or because the patient refused surgery (six patients). This group of clinical Stage I lung cancer patients is understaged by modern criteria since the majority of patients did not have thoracic CT scans and staging was based on fairly limited clinical and radiographic studies. The histological diagnosis was squamous cell carcinoma in 53% of the Stage I patients, adenocarcinoma in 25%, and other non-small cell histologies in 22%. All patients were treated with megavoltage irradiation and the mediastinum was treated in 88% of the patients. Eleven patients were treated with a continuous course (CC) and 32 patients received split course (SC) therapy based on physician preference. The CC consisted of a median fraction size of 200 cGy to a total median dose of 5900 cGy in 6-7 weeks. The SC used a median fraction site of 275 cGy to a total median dose of 5400 cGy over a 6-week period with a 2-week rest in the middle of treatment. The actuarial survival rate of the 43 clinical Stage I patients was 36% at 3 years and 21% at 5 years. Intrathoracic failures occurred in 39% of the patients. Despite the fact that the CC group was similar to the SC group in terms of age, histology, and tumor extent, the CC patients had a lower thoracic failure rate (2/11) versus 15/32), a longer median survival (51.6 months versus 27 months), and a better actuarial 5-year survival rate (45% versus 12%) when compared to the SC patients. Using Cox regression analysis to compare survival curves, the CC group had a significantly better survival compared to the SC group (p = .04).",
"This paper is a retrospective analysis of patients with clinical Stage I non-small cell carcinoma of the lung treated with definitive radiation therapy alone. The results of therapy, patterns of failure and the relationship of technical aspects of the delivery of radiotherapy to outcome are presented.\n From 1980 through 1990, 53 patients with Stage I non-small cell lung cancer were treated with definitive radiation therapy alone at the Radiation Oncology Center of the Mallinckrodt Institute of Radiology and its affiliated hospitals. All patients had a pathologic diagnosis of non-small cell lung cancer and were not candidates for surgical resection because of either patient refusal (10 patients), poor performance status (5 patients), or premorbid medical problems (38 patients). The median age was 73 years. Histologic cell type included squamous (32), adenocarcinoma (11), large cell (4), and unclassified non-small cell (6). Initial tumor size was < or = 3 cm in 23 patients, between 3 and 5 cm in 13 patients and > or = 5 cm in 17 patients. Diagnostic staging varied during the study period. All patients had chest X-rays and computed tomography scans of the chest. A majority had liver and bone scans, but only four underwent mediastinoscopy. The radiation therapy was of megavoltage energy in all patients, with a median primary prescription tumor dose of 63.2 Gy. Survival was measured from the date radiation therapy was initiated.\n The actuarial overall survival rate for the entire group was 19% at 3 years and 6% at 5 years, with a median survival time of 20.9 months. Of the 49 deaths, 35 died of lung cancer; 13 died of intercurrent illness, and one died of pancreatic cancer, which made the actuarial cause-specific survival 33% at 3 years and 13% at 5 years. The actuarial 3-year disease-free survival was 33%. Local primary tumor progression occurred in 22 patients, resulting in a 51% 3-year actuarial freedom from local progression. An additional four patients failed in regional lymph nodes that were included in the original treatment portals. Multivariate analysis found only T stage to be associated with overall survival (p = .02). However multivariate analysis showed age as a prognostic factor to be approaching statistical significance (p = .07). Patients under 70 years of age showed an increased survival rate compared to patients over 70 years. Radiation therapy doses > or = 65 Gy appeared to result in a decreased proportion of patients dying of lung cancer with no apparent increase in either acute or long-term complication rates.\n Results of definitive radiation therapy for inoperable Stage I non-small cell lung remain inferior to surgical therapy. Potential methods to improve local control with radiotherapy are discussed.",
"Eighty four patients from Groote Schuur Hospital and Frere Hospital East London were entered into a prospective randomised trial between January 1990 and December 1993. All the patients possessed non-small cell carcinoma (NSCLC) of the lung too extensive for radical irradiation and World Health Organization performance status 0-2. The patients were randomised to receive either 35 Gy in 10 fractions (43 patients) or 45 Gy in 15 fractions (41 patients). In the patients treated to 35 Gy and 45 Gy, the median survival was 8.5 months in both groups, the symptomatic response rate was 68% and 76% and the incidence of moderate to severe radiation oesophagitis was 23% and 41% respectively. The latter approached statistical significance (P = 0.07, chi square). There was no evidence of a dose response effect on survival in the moderate dose range in patients treated palliatively for locally advanced NSCLC.",
"For patients with locally or regionally advanced non-small-cell lung cancer radiation is the standard treatment, but survival remains poor. We therefore conducted a randomized trial to determine whether induction chemotherapy before irradiation improves survival.\n All the patients had documented non-small-cell cancer of the lung with Stage III disease established by clinical or surgical staging. Eligibility requirements included excellent performance status, minimal weight loss, and visible disease on radiography. Patients randomly assigned to group 1 received cisplatin (100 mg per square meter of body-surface area given intravenously on days 1 and 29) and vinblastine (5 mg per square meter given intravenously on days 1, 8, 15, 22, and 29) and then began radiation therapy on day 50 (60 Gy over a 6-week period). Patients assigned to group 2 received the same radiation therapy but began it immediately and received no chemotherapy.\n The eligible patients in group 1 (n = 78) and group 2 (n = 77) were comparable in terms of age (median, 60 years), sex, performance status, histologic features, stage of disease, and completeness of radiation therapy. The median survival was greater for those in group 1-13.8 versus 9.7 months (P = 0.0066 by log-rank test). Rates of survival in group 1 were 55 percent after one year, 26 percent after two years, and 23 percent after three years, as compared with 40, 13, and 11 percent, respectively, in group 2. Those in group 1 had a higher incidence of serious infections requiring hospitalization (7 percent, vs. 3 percent in group 2) and severe weight loss (14 percent vs. 6 percent), but there were no treatment-related deaths.\n In patients with Stage III non-small-cell lung cancer, induction chemotherapy with cisplatin and vinblastine before radiation significantly improves median survival (by about four months) and doubles the number of long-term survivors, as compared with radiation therapy alone. Since three quarters of the patients still die within three years, however, further improvements in systemic and local therapy are needed.",
"In order to obtain the standard treatment results of medically inoperable non-small cell lung cancer (NSCLC) in Stage I in the post-CT scan era, a retrospective analysis of patients who were treated by radical radiotherapy was performed.\n 149 cases treated between 1980 and 1989 were accumulated from ten large hospitals in Japan. All patients received a total dose of 55-75 Gy (mean 64.7 Gy) with conventional fractionation. For evaluation of treatment results, complete response (CR) rate, median survival period and long-termed survival rates were used.\n The median survival of the all cases was 27.2 months and the actuarial 3- and 5-year survival rates were 34.2% and 22.2%, respectively. CR was obtained in 57 cases (38%). The CR rate was strongly correlated with the long-term survival (5-year survival rate in CR group: 35.1% compared with PR + NC group: 14.1% (P < 0.0001)). The size of tumor was also of prognostic importance. In 116 patients who died within 5 years after treatment, 66 patients (57%) died of local tumor regrowth.\n Although the medically inoperable NSCLC patients in Stage I should be offered curative radiation therapy, development of some new steps to increase the CR rate and local control rate is urgently needed.",
"One hundred and fifty-three patients with inoperable non-small cell lung cancer (NSCLC) treated with radiotherapy alone have been retrospectively analysed. Normalized Total Dose (NTD) as defined by Macejewski, TN-stage (AJC-system) and histology have been examined with respect to 5-year disease-free survival (DFS) and the patterns of failure so as to identify subgroups of patients that routinely should be treated with radical intent. The 5-year DFS for T1, 2-N0, 1 and T3-N0, 1 staged patients was 30% (7/23) and 25% (4/16) respectively when the tumor NTD (a/b = 10 Gy) was 56-64 Gy vs. 12% (5/41) and 0% (0/10) when the NTD was 48-55 Gy. This difference was statistically significant for the squamous cell histology group. The higher doses significantly altered the patterns of death in N0, 1 staged squamous cell carcinoma and adenocarcinoma patients. Forty-five percent (22/55) and 41% (12/29) of squamous cell and adenocarcinoma patients respectively, died from local relapse without evidence of distant metastases when NTD less tha 55 Gy were given vs. 21% (9/42) and 13% (2/15) when the NTD delivered was 56-64 Gy (p < 0.05). Although for N2, 3 staged patients or patients with direct extension of the tumor into the mediastinum death from local relapse occurred in 38% (10/26) of the high NTD treated patients vs. 51% (19/37) of the low-dose treated ones, the difference was not statistically significant. It is concluded that NSCLC patients should not à priori be considered as non-radiocurable. At least 30% of the patients with early local stages can be long-term disease-free survivors with radiation NTD up to 60 Gy and better results are to be expected with higher doses. Advanced T-stage without mediastinal involvement should be treated with radical intent since a high NTD could give cure rates of over 25%. The disappointing results for patients with mediastinal disease could perhaps be attributed to the low NTD delivered. For patients with good performance status, hyperfractionated regimens delivering high tumor doses should be tested and chemotherapy should be adapted to these radiation treatment schedules.",
"In 38 cases of Stage I lung cancer, for which surgery was not indicated because of poor cardiopulmonary function or other reason, radical irradiation yielded excellent results. The five year survival rate was 42.1%, the 10-year survival rate 28.4% and the 15-year survival rate 17.1%. Postradiation complications which can be life-threatening, were acceptably low in incidence, and there was no radiation-related death. The results support the concept of radical irradiation being acceptable as a treatment modality for Stage I lung cancer if the patients concerned cannot have surgery because of poor cardiopulmonary function or some other reason.",
"The treatment results of radiotherapy in stage III non-small-cell lung cancer are very poor. Several phase II studies showed that neoadjuvant chemotherapy followed by radiotherapy was feasible in this patient group and suggested that treatment outcome might improve. A randomized phase II study was performed addressing the response rate and morbidity of high-dose split course radiotherapy (RT) versus the same radiotherapy preceded by high-dose chemotherapy (CT) in patients with stage III non-small-cell lung cancer.\n Seventy eligible patients were randomized in this study. CT consisted of cisplatin 100 mg/m2 days 1 and 22, and vindesine 3 mg/m2 on days 1, 8, 22 and 29. Radiotherapy started on day 43 in the combined arm and immediately in the RT-only arm. The primary tumour and the regional nodes were treated by 30 Gy/10 fractions/2 weeks and after the split by a second course of 25 Gy/10 fractions/2 weeks. In the combined arm a third CT cycle was planned during the split between RT courses.\n In the CT + RT arm 34 patients were evaluable for response and toxicity and 30 patients in the RT only arm. After completion of treatment 7 patients had a complete response (2 in the CT plus RT arm, 5 in the RT alone arm) and 26 patients a partial response (13 in the CT plus RT arm, 13 in the RT alone arm) for an overall response rate of 52% (95% CI 39%-65%). Acute toxicity was worse in the combined treatment arm with grade 4 leucocytopenia in 8 patients and thrombocytopenia grade 4 in one patient. Three patients had reversible renal toxicity grade 2. There was one toxic death in the RT plus CT arm. There was no enhancement of acute or late radiation pulmonary or oesophageal toxicity. Time to progressive disease (median 30 vs. 35 weeks) and overall survival time (median 12 months) were equal in both treatment arms.\n High-dose radiotherapy preceded by high-dose chemotherapy was more toxic than radiotherapy alone and did not result in this study in any benefit in terms of response rate, time to progressive disease and overall survival.",
"To evaluate the usefulness of radiation therapy alternative to surgery for clinical N0-N1 non-small cell lung cancer (NSCLC).\n From 1976 through 1989, 116 patients with NSCLC without mediastinal involvement were treated with definitive radiation therapy alone at Gunma University Hospital. All patients were treated with once-daily standard fractionation using 10 MV X-rays. The total dose ranged from 60 Gy to 80 Gy.\n The actuarial 2- and 5-year survival rates of the entire group were 43% and 20%, respectively with a median survival time of 19 months. The survival of 76 patients with stage T2 tumors was significantly better than that of 28 patients with T3 tumors (mean survival time 21 versus 15.5 months; p < 0.05). Sixty-two patients with tumors less than 5 cm in diameter had a 2-year progression rate of 20%, in comparison with 39% of 54 patients with tumors greater than 5 cm. The difference of survivals for these 2 groups was statistically significant. Twelve patients given a total dose of 80 Gy or more had only 17% local progression at the time of last follow-up, however, 5 of them developed severe stenosis of proximal bronchus after 6 to 15 months.\n These results should provide support for definitive radiation therapy using 60 to 70 Gy to manage the patients with medically inoperable NSCLC without mediastinal involvement.",
"High-dose radiation therapy is generally recommended as standard treatment in regionally advanced unresectable non-small-cell lung cancer (NSCLC), but median- and long-term survival remain poor. Some reports have recently shown an improvement of results in advanced NSCLC when cisplatin was included in the chemotherapy regimens. Therefore, we designed a randomized trial to determine whether induction chemotherapy before high-dose radiotherapy improves response rate and survival in stage III NSCLC over that achieved with radiotherapy alone.\n From March, 1984 to December, 1988, 66 consecutive patients with stage III unresectable NSCLC were randomized to one of two treatment arms; 61 were evaluable for survival and 58 for response and toxicity. Patients randomly assigned to arm A received cisplatin (CDDP 100 mg/m2 on day 1) and etoposide (VP 16 120 mg/m2 on days 1, 2, 3) every 3 wks for 3 courses followed by radiotherapy 56 Gy on pre-treatment tumor volume and 40 Gy on mediastinum and bilateral supraclavicular nodes. Patients assigned to arm B received only the same radiotherapy. The 61 eligible patients were comparable in terms of age, performance status, histology and treatment.\n Response rate was 53% in arm A and 32% in arm B. The median survival was 52 wks for the combined treatment arm and 36 wks for the radiation therapy arm. At six years of follow-up all the patients were dead. Toxicity was mild and no treatment-related deaths were recorded.\n Induction chemotherapy produced a better response rate and a trend of improved survival (4 months) but a significant survival advantage was not achieved (p < 0.11), probably because of the small number of patients enrolled in the trial.",
"To perform a randomized study of the optimal timing of thoracic radiation (RT) as accelerated hyperfractionated radiation therapy (ACC HFX RT) in combination with concurrent chemotherapy (CHT) in limited-stage small-cell lung cancer (SCLC).\n Between 1988 and 1992, 107 patients were enrolled and 103 were assessable. All patients received ACC HFX RT with 1.5 Gy twice daily to 54 Gy plus concurrent daily carboplatin/etoposide (C/E) (30 mg each) and four sequential cycles of cisplatin/etoposide (PE) (30 mg/m2 and 120 mg/m2, respectively, on days 1 to 3). Group I patients (n = 52) received concurrent chemoradiation at weeks 1 to 4, and group II (n = 51) at weeks 6 to 9. Patients who showed a complete response (CR) or partial response (PR) underwent prophylactic cranial irradiation (PCI) at weeks 16 to 17.\n The median survival time was 34 months in group I and 26 months in group II, and the Kaplan-Meier 5-year survival rates were 30% and 15%, respectively. The difference was almost significant on univariate analysis (P = .052) and was significant on multivariate analysis (P = .027). Group I patients had a significantly higher local control rate than group II patients, but there was no difference between the two groups in distant metastasis rate. There was no difference in the incidence of acute or late grade 3 to 4 toxicity.\n Initial administration of thoracic ACC HFX RT with concurrent C/E seems to produce better local control and survival rates than delayed administration.",
"To study the value of postoperative radiotherapy for non-small-cell lung cancer (NSCLC) with positive regional lymph metastases (NI or N2) after radical surgery.\n From February 1982 to October 1995, 366 patients with NSCLC and N1 or N2 disease were randomized into postoperative radiotherapy (S + R) (183 patients) and no further treatment (S alone) (182 patients). Postoperative radiotherapy (RT) was administrated 3-4 weeks after radical operation. Irradiated fields covered the bronchial stump, ipsilateral hilum, and most of the mediastinum. The midplane dose was 6000 cGy/30 fractions/6 weeks, with the spinal cord limited to 4000 cGy/20 fractions/4 weeks or less. One hundred thirty-four patients in S + R group and 162 patients in S alone group were evaluated. Clinical data were comparable in both arms, except for the numbers of N2 patients.\n The 3-year and 5-year overall survival rates were 51.9% and 42.9% in the S + R group and 50.2% and 40.5% in the S alone Group (p = 0.56). The 3-year and 5-year disease-free survival rates were 50.7% +/- 4.7% and 42.9% +/- 5.2% in the S + R group vs. 44.4% +/- 4.3% and 38.2% +/- 4.5% in the S alone group (p = 0.28), respectively. In the patients with NI or T3-4 tumors, there was a trend toward improved survival in the S + R group, especially in the patients with T3-4N1M0. These patients demonstrated 20% improvement in overall survival (p = 0.092) and greater than 20% better disease-free survival (p = 0.057). Postoperative RT reduced local recurrence but had no impact on distant metastases.\n Postoperative RT significantly reduced local relapses, but did not improve overall survival, due to a high frequency of distant metastases in this patient group.",
"The outcome of limited field irradiation for medically inoperable patients with peripheral stage I non-small cell lung cancer (NSCLC) was analyzed to discuss the elective irradiation of regional lymph nodes. From 1976 through 1994, 36 patients with peripheral stage I NSCLC were treated with definitive radiation therapy (RT) alone at Gunma University hospital. The total dose ranged from 60 to 81 Gy with a 2 Gy-daily standard fractionation, although only one patient received 48 Gy. Ten patients received elective irradiation of the regional lymph nodes with a total dose of 40 Gy or more. The overall response rate was 97% with 31% complete responses. The overall survival rates at 3 and 5 years were 42 and 23%, and disease-specific survival rates were 56 and 39% at 3 and 5 years, respectively. In 26 patients without the elective regional irradiation, disease-specific survival rates at 3 and 5 years were 53 and 40%, respectively, whereas they were 64 and 39% in 10 patients with the regional nodal irradiation. The cumulative 5-year local progression rate was 28%, and the overall progression rate was 60% at 5 years. Four patients had a local recurrence as the only site of initial tumor progression. Combined local and regional progression was seen in two patients, and one patient had a local recurrence in combination with distant metastasis. Twelve patients had distant failure without evidence of local or regional progression. Only one patient without regional nodal irradiation developed an isolated regional failure. No patient had serious complications related to RT. High-dose limited field RT is justified for medically inoperable patients with peripheral stage I NSCLC. The regional nodal irradiation can be omitted in these pulmonary compromised patients because of the low regional relapse rate. Dose-escalation by a conformal RT with a small target volume can be expected to provide a better local control rate and better survival.",
"To evaluate if the timing of chest irradiation with respect to chemotherapy would influence survival and local and distant control in patients with limited-stage small-cell lung cancer (LSCLC).\n From 1981 to 1989, 199 consecutive patients with LSCLC were randomly allocated to receive initial chest irradiation (ICI; n = 99) or late chest irradiation (LCI; n = 100) given 18 weeks delayed. Both groups received the same nine cycles of combination chemotherapy: three cycles of cisplatin and etoposide and six cycles of cyclophosphamide, doxorubicin, and vincristine. In the first part of the study, prophylactic cranial irradiation (PCI) was only given to patients randomized to ICI, but after inclusion of 42 patients in the LCI arm, the protocol was changed, so that all patients received PCI independent of the timing of the chest irradiation (CI). A total of 157 patients received PCI with a radiation dose of 25 Gy in 11 fractions.\n The timing of radiotherapy had no significant effect on the 2-year overall survival rate (20% after ICI v 19% after LCI, P = .4) or the 2-year in-field recurrence rate (72% after ICI v 68% after LCI, P = .2). Median survival durations were 10.5 (ICI) and 12.0 (LCI) months. Similarly, no difference in the 2-year incidence of CNS recurrences was found between the 2 arms in patients who received PCI (19% after ICI v 13% after LCI, P = .24). Bone marrow toxicity was acceptable, as 15% developed World Health Organization (WHO) grade 4 leukocytopenia and 4% grade 4 thrombocytopenia. Grade 4 leukocytopenia was more pronounced in the ICI group. There was no difference in the frequency and severity of other toxicities between the 2 groups.\n Timing of CI did not significantly influence the incidence of in-field recurrences, CNS recurrences, or overall survival."
] |
There were no randomised trials that compared a policy of immediate radical radiotherapy with palliative radiotherapy given when patients develop symptoms. In the absence of such trials, radical radiotherapy appears to result in a better survival than might be expected had treatment not been given. A substantial, though variable, proportion of patients died during follow-up from causes other than cancer. The optimal radiation dose and treatment technique (particularly with respect to mediastinal irradiation) remain uncertain.
|
CD006640
|
[
"3101804",
"395630",
"16935098",
"8607670",
"10962414",
"6353843",
"12118485"
] |
[
"Tranexamic acid as an aid to reducing blood transfusion requirements in gastric and duodenal bleeding.",
"Tranexamic acid in massive haemorrhage from the upper gastrointestinal tract: a double-blind study.",
"A randomized trial of tranexamic acid in combination with cell salvage plus a meta-analysis of randomized trials evaluating tranexamic acid in off-pump coronary artery bypass grafting.",
"Tranexamic acid reduces postbypass blood use: a double-blinded, prospective, randomized study of 210 patients.",
"Tranexamic acid compared with high-dose aprotinin in primary elective heart operations: effects on perioperative bleeding and allogeneic transfusions.",
"Tranexamic acid and traumatic hyphaema. A prospective study.",
"Tranexamic acid in patients with hemoptysis."
] |
[
"A prospective randomised double blind study examined the effect of the antifibrinolytic drug tranexamic acid compared with placebo in 154 patients bleeding from verified benign lesions in the stomach or duodenum or both. Three out of 72 patients receiving tranexamic acid underwent emergency surgery compared with 15 out of 82 given placebo (p = 0.010). Nineteen patients receiving placebo rebled during their admission as compared with 10 in the active treatment group (p = 0.097). Blood transfusion requirements were significantly reduced by tranexamic acid (p = 0.018). Side effects occurred in six patients, of which an uncomplicated deep venous thrombosis was the most severe. Tranexamic acid reduces the blood transfusion requirement and need for emergency surgery in patients bleeding from a benign gastric or duodenal lesion.",
"In a double-blind trial of tranexamic acid in massive upper gastrointestinal haemorrhage, 76 patients were treated with the active drug and 73 patients with placebo. The doses were 1 g intravenously six times daily for a maximum of 3 days, followed by 1.5 g orally four times daily for a maximum of 4 days. The treatment group and the placebo group were comparable with respect to mean age, diagnoses and laboratory tests but differed slightly with respect to sex and alcohol consumption. The transfusion requirement in the treatment group was less than in the placebo group during the first days after admission, the difference being significant on the second day after admission. Ten patients in the treatment group and 18 patients in the placebo group were operated on. Eleven patients in the treatment group and 12 patients in the placebo group died. In the tranexamic-acid-treated group fewer operations were performed and significantly less blood was needed. It therefore seems highly likely that tranexamic acid has a beneficial effect, although small.",
"We sought to evaluate the effectiveness of tranexamic acid in off-pump coronary artery bypass grafting surgery, either when used in combination with mechanical cell salvage or when used alone.\n One hundred patients were randomized to either 2 g of tranexamic acid as an intravenous bolus before sternotomy or to placebo. Intraoperative and postoperative cell salvage was used in all patients. The primary end point was early postoperative blood loss (within 4 hours). To evaluate the efficacy of tranexamic acid in isolation, we also performed a meta-analysis of 4 randomized trials identified from a systematic literature search. The primary end point of the meta-analysis was red cell transfusion.\n In our randomized trial patients in the tranexamic acid group had a significant reduction in early postoperative blood loss, (median difference, 50 mL; 95% confidence interval, 15-100 mL; P < .01); however, there was no reduction in the frequency of blood component transfusion. Patients in the placebo group received a significantly larger volume of autotransfused red cells (median difference, 120 mL; 95% confidence interval, 0-220 mL; P = .02). The meta-analysis demonstrated a significant reduction in red cell transfusions in patients receiving tranexamic acid compared with those receiving placebo (risk ratio, 0.48; 95% confidence interval, 0.24-0.97; P = .041). There was also a reduction in the frequency of any allogeneic blood component transfusion, as well as a highly significant reduction in postoperative blood loss, in patients receiving tranexamic acid (P < .001).\n Tranexamic acid reduces blood loss and transfusion requirements in off-pump coronary artery bypass grafting surgery. A reduction in allogeneic blood transfusion was not evident in the presence of perioperative cell salvage. These data support the routine use of tranexamic acid in off-pump coronary artery bypass grafting surgery.",
"Pharmacologic intervention to minimize postbypass bleeding and blood product transfusions has received increasing attention for both medical and economic reasons.\n Two hundred ten patients were entered into a double-blinded, prospective, randomized study to receive either 10 g of fibrinolytic inhibitor tranexamic acid before incision (n = 104) or 250 mL of placebo saline solution (n = 106). All subjects requiring cardiopulmonary bypass were deemed suitable, including those having first-time coronary bypass grafting, valve replacement, and reoperation.\n There were no statistically significant differences between the groups with respect to demographic or operative characteristics. The tranexamic acid group had a 48% reduction in 24-hour blood drainage (p < 0.001) and received 69% fewer total units of packed red blood cells, 83% fewer total units of plasma, and 75% fewer platelet transfusion units than controls. Only 13 of 104 tranexamic acid patients received blood products versus 33 of 106 controls (p < 0.001). The incidences of thrombotic complications, perioperative myocardial infarction, renal failure, and neurologic complications were not significantly different between the two groups. The tranexamic acid group had 0% mortality versus 1.9% for controls (not significant).\n Tranexamic acid is safe and effective in reducing blood loss and blood use in a wide variety of cardiac surgical patients.",
"Since excessive fibrinolysis during cardiac surgery is frequently associated with abnormal perioperative bleeding, many authors have advocated prophylactic use of antifibrinolytic drugs to prevent hemorrhagic disorders. We compared the effects of tranexamic acid (a synthetic antifibrinolytic drug) with aprotinin (a natural derivative product with antifibrinolytic properties) on perioperative bleeding and the need for allogeneic transfusions.\n In a single-center prospective randomized unblinded trial, 1040 consecutive patients undergoing primary, elective cardiac operations with cardiopulmonary bypass received either high-dose aprotinin or tranexamic acid. The aprotinin group (518 patients) received 280 mg in 20 minutes before the skin incision, 280 mg in the priming solution of the extracorporeal circuit, and a continuous infusion of 70 mg/h throughout the operation. The tranexamic acid group (522 patients) received 1 g in 20 minutes before the skin incision, 500 mg in the priming solution of the extracorporeal circuit, and a continuous infusion of 400 mg/h during the operation. Postoperative bleeding, perioperative transfusions, and hematologic variables were evaluated at fixed times. Postoperative thrombotic complications, intubation time, intensive care unit stay, and hospital stay were recorded.\n Postoperative bleeding was similar in the 2 groups: aprotinin 250 mL (150-400 mL) versus tranexamic acid 300 mL (200-450 mL) (median and 25th-75th quartiles), median difference of 50 mL (95% confidence intervals, 0-50 mL). The number of transfusions and the outcome did not differ.\n Tranexamic acid and aprotinin show similar clinical effects on bleeding and allogeneic transfusion in patients undergoing primary elective heart operations. Since tranexamic acid is about 100 times cheaper than aprotinin, its use is preferable in this type of patient.",
"112 patients with traumatic hyphaema were investigated prospectively over a period of 3 years. 53 had conservative treatment and 59 tranexamic acid treatment. They were hospitalized, but fully mobilized. Both groups were given supplementary local therapy with glucocorticoids and mydriatics as well as monocular patching. In neither group was any re-bleeding seen. The resorption of blood was delayed in the tranexamic treated patients, which may be taken as indirect proof of the efficacy of the treatment. The longer persistence of blood in the anterior chamber in the tranexamic acid treated group caused no complication. The treatment was well tolerated. In both departments treatment with tranexamic acid had replaced the bed rest treatment.",
"Hemoptysis is a common respiratory symptom leading to admission to hospital. The main management of hemoptysis depends on treating the underlying cause. The use of tranexamic acid is recommended by many doctors without much information available.\n This study was a randomized double blinded placebo controlled trial in using tranexamic acid (Transamine) in hemoptysis patients. The study period was one week. Patients with hemoptysis were separated into 3 groups depending on the amount of blood. Group 1 consisted of patients with blood streak sputum. Group 2 coughed up less than 20 ml of frank blood. Patients in Group 3 were those who coughed up 20-500 ml of blood per day. A record of the amount of bleeding and drug side effects was done.\n From June 1994 to May 1997, 46 patients with hemoptysis completed the study. There were 21 in the tranexamic acid group and 25 in the placebo group. The placebo group had a tendency not to have underlying lung disease and more patients who had a normal chest X-ray. The benefit of tranexamic acid in shortening the days of hemoptysis is not shown in this study. There was a low incidence of side effects of tranexamic acid in this study.\n This randomized double blinded placebo controlled trial could not demonstrate the benefit of tranexamic acid in shortening the days of hemoptysis and confirm the low incidence of side effects of this drug."
] |
Considering the internal and external validity of the evidence, tranexamic acid cannot be recommended for routine use. Additional trials in which tranexamic acid is used in combination with the currently recommended interventions are required.
|
CD006480
|
[
"15990772",
"15802340",
"15100668",
"8831855",
"15480319",
"3545094",
"20477733",
"16815138",
"16176400",
"17892588",
"14718266",
"10484799"
] |
[
"The Canadian Childhood Asthma Primary Prevention Study: outcomes at 7 years of age.",
"The PREVASC study: the clinical effect of a multifaceted educational intervention to prevent childhood asthma.",
"The Canadian asthma primary prevention study: outcomes at 2 years of age.",
"Effects of a dietary and environmental prevention programme on the incidence of allergic symptoms in high atopic risk infants: three years' follow-up.",
"Three-year outcomes of dietary fatty acid modification and house dust mite reduction in the Childhood Asthma Prevention Study.",
"Asthma education by community child health nurses.",
"An education intervention for childhood asthma by Aboriginal and Torres Strait Islander health workers: a randomised controlled trial.",
"Prevention of asthma during the first 5 years of life: a randomized controlled trial.",
"Three-year follow-up of clinical and inflammation parameters in children monosensitized to mites undergoing sub-lingual immunotherapy.",
"Educational outreach to general practitioners reduces children's asthma symptoms: a cluster randomised controlled trial.",
"Specialist nurse intervention to reduce unscheduled asthma care in a deprived multiethnic area: the east London randomised controlled trial for high risk asthma (ELECTRA).",
"A randomized clinical trial to reduce asthma morbidity among inner-city children: results of the National Cooperative Inner-City Asthma Study."
] |
[
"Avoidance of any one of the individual risk factors associated with childhood asthma has not been successful in preventing its development.\n The purpose of this study is to determine the effectiveness of a multifaceted intervention program for the primary prevention of asthma in high-risk infants at 7 years of age.\n Five hundred forty-five high-risk infants with an immediate family history of asthma and allergies were prospectively randomized into intervention or control groups prenatally. Intervention measures introduced before birth and during the first year of life included avoidance of house dust, pets, and environmental tobacco smoke and encouragement of breast-feeding with delayed introduction of solid foods. Assessment of outcomes at 7 years consisted of examination by pediatric allergists, methacholine inhalation tests, and allergy skin tests.\n At 7 years, 469 of the 545 children were contacted, and 380 returned for further assessment. The prevalence of pediatric allergist-diagnosed asthma was significantly lower in the intervention group than in the control group (14.9% vs 23.0%; adjusted risk ratio, 0.44; 95% CI, 0.25-0.79). The prevalence of allergic rhinitis, atopic dermatitis, atopy (defined as positive skin test reactions to any common allergen), and bronchial hyperresponsiveness (defined as the provocative concentration of methacholine that induced a 20% decrease in FEV 1 from a postsaline value of less than 7.8 mg/mL) were not significantly different between the 2 groups. The prevalence of asthma (defined as wheeze without colds and the presence of bronchial hyperresponsiveness) was also significantly lower in the intervention group compared with the control group (12.9% vs 25.0%; adjusted risk ratio, 0.39; 95% CI, 0.22-0.71).\n The multifaceted intervention program was effective in reducing the prevalence of asthma in high-risk children at 7 years of age.",
"As asthma is the most common chronic disease in childhood, much attention is directed towards primary prevention. Here, the clinical effectiveness of a multifaceted educational prevention was studied. A total of 476 high-risk children were recruited during the prenatal period by general practitioners and randomised to either: 1) a control group, receiving usual care; or 2) an intervention group in which families received instruction from nurses on how to reduce exposure of newborns to mite, pet and food allergens, and passive smoking. A total of 443 infants were followed-up for 2 yrs. At 2 yrs of age, the intervention group (n = 222) had less asthma-like symptoms, including wheezing, shortness of breath and night-time cough, than the control group (n = 221). No significant differences in total and specific immunoglobulin E were found between the groups. During the first 2 yrs of life, the incidence of asthma-like symptoms was similar in both groups; however, subanalysis revealed a significant reduction in the female, but not in the male, intervention group. In conclusion, the intervention used in this study was not effective in reducing asthma-like symptoms in high-risk children during the first 2 yrs of life, although it was modestly effective at 2 yrs. Follow-up is necessary to confirm whether the intervention can actually prevent the development of asthma.",
"Avoidance of individual risk factors have not been successful in preventing the development of asthma.\n We sought to determine the effectiveness of a multifaceted intervention program in primary prevention of asthma in high-risk infants.\n We identified 545 high-risk infants on the basis of an immediate family history of asthma. Families were randomized into intervention or control groups. Intervention measures included avoidance of house dust mite, pet allergen, and environmental tobacco smoke. Breast-feeding was encouraged with formula supplementation if necessary, and introduction of solid foods was delayed.\n At 2 years of age, 19.5% of the children had asthma, and 14.7% had atopy (positive skin test response to one or more common allergens). Significantly fewer children had asthma in the intervention group compared with in the control group (16.3% vs 23.0%), with 60% less persistent asthma at 2 years. There was a 90% reduction for recurrent wheeze in the intervention group compared with that seen in the control group. Exposure to maternal environmental tobacco smoke during pregnancy or the first year was a risk factor for asthma at 2 years of age. A positive skin test response, particularly to food, at 12 months predicted asthma at 2 years. There was no significant difference for atopy between the intervention and control groups, but daycare reduced atopy at 2 years.\n This multifaceted intervention program during a window of opportunity in the first year of life was effective in preventing asthma in high-risk children at 2 years of age. Future studies with this cohort at school age are important.",
"A prospective case-control study is presented to assess an allergy prevention programme in children up to 36 months of age. Infants born at three maternity hospitals were followed from birth: 279 infants with high atopic risk (intervention group) were compared with 80 infants with similar atopic risk but no intervention (non-intervention group). The intervention programme included dietary measures (exclusive and prolonged milk feeding diet followed by a hypoantigenic weaning diet) and environmental measures (avoidance of parental smoking in the presence of the babies, day care > 2 years of life). Mothers in this group who had insufficient breast milk were randomly assigned to one of two coded formulas: either a hydrolysed milk formula (Nidina HA, Nestlé) or a conventional adapted formula (Nan, Nestlé). Other environmental measures remained the same as for the breastfeeding mothers. The non-intervention group were either breastfed or received the usual Italian milk feeding and weaning diet, without environmental advice. The main outcome measures were anthropometric measurements and allergic disease manifestations. Normal anthropometric data were observed both in the intervention group and in the non-intervention group. The incidence of allergic manifestations was much lower in the intervention group than in the non-intervention group at 1 year (11.5 versus 54.4%, respectively) and at 2 years (14.9 versus 65.6%) and 3 years (20.6 versus 74.1%). Atopic dermatitis and recurrent wheezing were found in both the intervention group and the non-intervention group from birth up to the second year of life, while urticaria and gastrointestinal disorders were only present in the non-intervention group in the first year of life. Conjunctivitis and rhinitis were present after the second year in both the intervention group and the non-intervention group. Relapse of the same allergic symptom was less in the intervention group (13.0%) than in the non-intervention group (36.9%). In comparison to the non-intervention group, there were fewer intervention group cases with two or more different allergic symptoms (8.7 versus 32.6%), and they were more likely to avoid steroid treatment (0 versus 10.8%) and hospital admission (0 versus 6.5%). Babies in the non-intervention group fed with adapted formula were more likely to develop allergies than breastfed babies in the same group. In the intervention group the breastfed infants had the lowest incidence of allergic symptoms, followed by the infants fed the hydrolysed formula (ns). Infants in the intervention group fed the adapted formula had significantly more allergies than the breastfed and hydrolysed milk fed infants, although less than their counterparts in the non-intervention group. Of the affected subjects in the intervention group, 80.4% were RAST and/or Prick positive to food or inhalant allergens. Total serum IgE values detected at birth in the intervention group were not predictive, but at 1 and 2 years of age, IgE values more than 2 SD above the mean in asymptomatic babies were found to predictive for later allergy. In breastfed babies the total IgE level at 1 and 2 years of age was lower than in the other two feeding groups. Of the various factors tested in the non-intervention group, the following were the most important in the pathogenesis of allergic symptoms: (i) formula implementation begun in the first week of life; (ii) early weaning (< 4 months); (iii) feeding beef (< 6 months); (iv) early introduction of cow's milk (< 6 months); and (v) parental smoking in the presence of the babies and early day care admission (< 2 years of life). All the preventive measures used in this study (exclusive breastfeeding and/or hydrolysed milk feeding, delayed and selective introduction of solid foods, and environmental advice) were effective at the third year of follow-up, greatly reducing allergic manifestations in high atopic risk babies in comparison with those not receiving these interventions",
"Two factors thought to influence the risk of asthma are the promoting effect of sensitization to house dust mites and the preventive effect of increased omega-3 fatty acids. Although house dust mite allergen avoidance has been used as a preventive strategy in several trials, the effect of omega-3 fatty acid supplementation in the primary prevention of asthma and allergic disease is not known.\n To measure the effects of dietary supplementation with omega-3 fatty acids and house dust mite allergen avoidance in children with a family history of asthma.\n A total of 616 children at high risk of asthma were enrolled antenatally in a randomized controlled trial, and 526 children remained in the trial at age 3 years. The outcomes were symptoms of allergic disease and allergen sensitization.\n There was a significant 10.0% (95% CI, 3.7-16.4) reduction in the prevalence of cough in atopic children in the active diet group ( P=.003; number needed to treat, 10) but a negligible 1.1% (95% CI, -7.1 to 9.5) reduction cough among nonatopic children. There was a 7.2% (95% CI, 10.11-14.3) reduction in sensitization to house dust mite in the active allergen avoidance group ( P=.05; number needed to treat, 14). No significant differences in wheeze were found with either intervention.\n These results suggest that our interventions, designed to be used in simple public health campaigns, may have a role in preventing the development of allergic sensitization and airways disease in early childhood. This offers the prospect of reducing allergic disease in later life.",
"A randomised controlled study of an educational programme for children with asthma and their families was carried out by community child health nurses. Three hundred and sixty eight children aged 2 to 14 years were enrolled in the study after admission to hospital for asthma. The intervention group was visited monthly by a nurse for six months. The subjects were assessed six months later by a postal, self administered questionnaire. European children in the intervention group were taking significantly more drugs for the treatment of asthma six months after the index admission to hospital than those in the control group (mean (SD) intake 2.7 (1.1) v 2.1 (1.0), respectively). In particular, they were using more theophylline (56.6% v 37.0%) and inhaled steroids (34.9% v 21.0%). There was no difference between the groups for parental reports of improvement, of missed schooling, and in severe attacks of asthma of not responding to the usual treatment at home. European children in the intervention group used the hospital services for severe attacks of asthma more than controls (34.2% v 10.5%). There were more re-admissions in the European intervention group in the subsequent six months after the index admission than in the control group (mean (SD) 0.51 (0.97) v 0.29 (0.65). Re-admission continued to be higher in the 12 months after the nurse had stopped visiting (0.81 (1.65) v 0.25 (0.65]. There was no difference in the duration of hospital stay between the intervention and control groups. For Polynesian children there was no difference between the groups for any outcome measures.",
"To assess the outcomes of an education intervention for childhood asthma conducted by Australian Indigenous health care workers (IHCWs).\n Randomised controlled trial in a primary health care setting on Thursday Island and Horn Island, and in Bamaga, Torres Strait region of northern Australia, April 2005 to March 2007.\n 88 children, aged 1-17 years, with asthma diagnosed by a respiratory physician (intervention group, 35; control group, 53; 98% Indigenous children).\n Children were randomly allocated to: (i) three additional asthma education sessions with a trained IHCW, or (ii) no additional asthma education. Both groups were re-assessed at 12 months.\n Primary endpoint: number of unscheduled visits to hospital or a doctor caused by asthma exacerbation. Secondary outcomes: measures of quality of life (QoL) and functional severity index; asthma knowledge and understanding of asthma action plans (AAPs); and school days missed because of wheezing.\n The groups were comparable at baseline (except for asthma severity, which was adjusted for in the analysis). There were no significant differences in the primary outcome (number of unscheduled medical visits for asthma). School children in the intervention group missed fewer school days because of wheezing (100% < 7 days v 21% of those in the control group missed 7-14 days). Significantly more carers in the intervention group could answer questions about asthma medication, knew where their AAP was kept (84% v 56%), and were able to describe the plan (67% v 40%). In both the intervention and control groups (before-and-after comparison), there was a significantly reduced frequency of asthma exacerbations, as well as an improved QoL score and functional severity index, with no significant differences between the groups.\n A community-based asthma education program conducted by trained IHCWs improves some important asthma outcomes in Indigenous children with asthma.\n Australian Clinical Trials Registry ACTRN012605000718640.",
"Early life exposures may be important in the development of asthma and allergic disease.\n To test house dust mite (HDM) avoidance and dietary fatty acid modification, implemented throughout the first 5 years of life, as interventions to prevent asthma and allergic disease.\n We recruited newborns with a family history of asthma antenatally and randomized them, separately, to HDM avoidance or control and to dietary modification or control. At age 5 years, they were assessed for asthma and eczema and had skin prick tests for atopy.\n Of 616 children randomized, 516 (84%) were evaluated at age 5 years. The HDM avoidance intervention resulted in a 61% reduction in HDM allergen concentrations (microg/g dust) in the child's bed but no difference in the prevalence of asthma, wheeze, or atopy (P > .1). The prevalence of eczema was higher in the active HDM avoidance group (26% vs 19%; P = .06). The ratio of omega-6 to omega-3 fatty acids in plasma was lower in the active diet group (5.8 vs 7.4; P < .0001). However, the prevalence of asthma, wheezing, eczema, or atopy did not differ between the diet groups (P > .1).\n Further research is required to establish whether other interventions can be recommended for the prevention of asthma and allergic disease.\n House dust mite avoidance measures and dietary fatty acid modification, as implemented in this trial during infancy and early childhood, did not prevent the onset of asthma, eczema, or atopy in high-risk children.",
"Parallel follow-up of clinical and inflammatory markers during sub-lingual immunotherapy (SLIT) is highly beneficial. Twenty-four children (age 4-16) monosensitized to house dust mite were randomized to receive either active or placebo SLIT for 1 yr in a double-blind placebo controlled design (Marcucci et al., Allergy 2003: 58: 657-62). Thereafter, for 2 yr they all received active treatment. Symptom scores for rhinitis, asthma, and drug usage were daily recorded. Eosinophil cationic protein (ECP) and tryptase in sputum and nasal secretions, serum and nasal mite-specific immunoglobulin E (IgE) were recorded before treatment and at 10-12 months intervals. Nasal ECP and nasal tryptase after specific nasal provocation tests were significantly reduced as compared to baseline values (p = 0.0043 and 0.0195, respectively) in the third year of active treatment. None of the other inflammatory parameters was increased. In placebo treated patients all these parameters tended to decrease only after switching to active treatment. Clinical scores did not improve in treated vs. placebo patients in the double-blind placebo-controlled phase of the study. In both cohorts a clinical benefit was observed as intra-group score reduction as compared to baseline. A significant difference was reached in patients treated for 2 yr for rhinitis and asthma (p = 0.0009 and 0.0019, respectively) but not for drug usage and in patients treated for 3 yr for rhinitis, asthma, and drug usage (p = 0.0105, 0.0048, and 0.02, respectively). SLIT in children monosensitized to mites reverted the spontaneous increase in nasal IgE and in local parameters of allergic inflammation. These outcomes were followed by a consolidated clinical improvement in the second and third year of treatment.",
"Childhood asthma is common in Cape Town, a province of South Africa, but is underdiagnosed by general practitioners. Medications are often prescribed inappropriately, and care is episodic. The objective of this study is to assess the impact of educational outreach to general practitioners on asthma symptoms of children in their practice.\n This is a cluster randomised trial with general practices as the unit of intervention, randomisation, and analysis. The setting is Mitchells Plain (population 300,000), a dormitory town near Cape Town. Solo general practitioners, without nurse support, operate from storefront practices. Caregiver-reported symptom data were collected for 318 eligible children (2 to 17 years) with moderate to severe asthma, who were attending general practitioners in Mitchells Plain. One year post-intervention follow-up data were collected for 271 (85%) of these children in all 43 practices. Practices randomised to intervention (21) received two 30-minute educational outreach visits by a trained pharmacist who left materials describing key interventions to improve asthma care. Intervention and control practices received the national childhood asthma guideline. Asthma severity was measured in a parent-completed survey administered through schools using a symptom frequency and severity scale. We compared intervention and control group children on the change in score from pre-to one-year post-intervention.\n Symptom scores declined an additional 0.84 points in the intervention vs. control group (on a nine-point scale. p = 0.03). For every 12 children with asthma exposed to a doctor allocated to the intervention, one extra child will have substantially reduced symptoms.\n Educational outreach was accepted by general practitioners and was effective. It could be applied to other health care quality problems in this setting.",
"To determine whether asthma specialist nurses, using a liaison model of care, reduce unscheduled care in a deprived multiethnic area.\n Cluster randomised controlled trial.\n 44 general practices in two boroughs in east London.\n 324 people aged 4-60 years admitted to or attending hospital or the general practitioner out of hours service with acute asthma; 164 (50%) were South Asian patients, 108 (34%) were white patients, and 52 (16%) were from other, largely African and Afro-Caribbean, ethnicities.\n Patient review in a nurse led clinic and liaison with general practitioners and practice nurses comprising educational outreach, promotion of guidelines for high risk asthma, and ongoing clinical support. Control practices received a visit promoting standard asthma guidelines; control patients were checked for inhaler technique.\n Percentage of participants receiving unscheduled care for acute asthma over one year and time to first unscheduled attendance.\n Primary outcome data were available for 319 of 324 (98%) participants. Intervention delayed time to first attendance with acute asthma (hazard ratio 0.73, 95% confidence interval 0.54 to 1.00; median 194 days for intervention and 126 days for control) and reduced the percentage of participants attending with acute asthma (58% (101/174) v 68% (99/145); odds ratio 0.62, 0.38 to 1.01). In analyses of prespecified subgroups the difference in effect on ethnic groups was not significant, but results were consistent with greater benefit for white patients than for South Asian patients or those from other ethnic groups.\n Asthma specialist nurses using a liaison model of care reduced unscheduled care for asthma in a deprived multiethnic health district. Ethnic groups may not benefit equally from specialist nurse intervention.",
"To evaluate a family-focused asthma intervention designed for inner-city children 5 to 11 years old with moderate to severe asthma.\n Randomized, multisite, controlled trial to minimize symptom days (wheeze, loss of sleep, reduction in play activity) measured by a 2-week recall assessed at 2-month intervals over a 2-year follow-up period. The intervention was tailored to each family's individual asthma risk profile assessed at baseline.\n Averaged over the first 12 months, participants in the intervention group (n = 515) reported 3.51 symptom days in the 2 weeks before each follow-up interview compared with 4.06 symptom days for the control group (n = 518), a difference of 0.55 (95% CI, 0.18 to 0.92, P =.004). The reduction among children with severe asthma was approximately 3 times greater (1.54 d/2 wk). More children in the control group (18.9%) were hospitalized during the intervention compared with children in the intervention group (14. 8%), a decrease of 4.19% (CI, -8.75 to 0.36, P =.071). These improvements were maintained in the intervention group during the second year of follow-up, during which they did not have access to the asthma counselor.\n We demonstrated that an individually tailored, multifaceted intervention carried out by Masters-level social workers trained in asthma management can reduce asthma symptoms among children in the inner city."
] |
The available evidence suggests that the reduction of exposure to multiple allergens compared to usual care reduces the likelihood of a current diagnosis of asthma in children (at ages < 5 years and 5 years and older). Mono-intervention studies have not produced effects which are statistically significant compared with control. In children who are at risk of developing childhood asthma, multifaceted interventions, characterised by dietary allergen reduction and environmental remediation, reduce the odds of a physician diagnosis of asthma later in childhood by half. This translates to a number needed to treat (NNT) of 17. The effect of multi-faceted interventions on parent reported wheeze was inconsistent and had no significant impact on nocturnal coughing or dyspnoea. Data from monofaceted intervention exposed children studies were not significantly different from those of control groups for all outcomes. There remains uncertainty as to whether multiple interventions are more effective than mono-component interventions. The comparisons made were indirect, making the conclusions drawn uncertain. To our knowledge there are no ongoing studies in which both intervention strategies are randomly compared. The findings, however, warrant further direct comparison between multiple- and monofaceted interventions aimed at reducing the prevalence of asthma in children.
|
CD001876
|
[
"8553306",
"15295690",
"2233917",
"1613673"
] |
[
"Randomised trial of corticosteroids in the treatment of tuberculous pleurisy.",
"A randomized, double-blind, placebo-controlled trial of the use of prednisolone as an adjunct to treatment in HIV-1-associated pleural tuberculosis.",
"A controlled trial of early adjunctive treatment with corticosteroids for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. California Collaborative Treatment Group.",
"Adjunctive corticosteroid therapy for Pneumocystis carinii pneumonia in AIDS: a randomized European multicenter open label study."
] |
[
"Tuberculous pleurisy can result in pleural fibrosis, calcification and thickening. To prevent these complications, corticosteroids are frequently used in addition to antituberculous drugs; however, new therapeutic regimens can control the disease and minimise the sequelae, and there is no convincing evidence of the benefit of the use of corticosteroids as adjuvant therapy.\n Patients received isoniazid 5 mg/kg and rifampicin 10 mg/kg daily for six months. Additionally, they were randomly assigned to a double blind treatment with either prednisone (1 mg/kg/day for 15 days and then tapering off) or placebo during the first month of treatment. Different clinical, radiological, and functional parameters were evaluated to assess the effect of corticosteroids.\n Fifty seven patients received prednisone and 60 placebo. At the end of the treatment the clinical outcome, the rate of reabsorption of the pleural fluid, the pleural sequelae, as well as lung capacity were similar in both groups.\n Corticosteroids do not influence the clinical outcome or the development of long term pleural sequelae in tuberculous pleurisy.",
"Active tuberculosis may accelerate progression of human immunodeficiency virus (HIV) infection by promoting viral replication in activated lymphocytes. Glucocorticoids are used in pleural tuberculosis to reduce inflammation-induced pathology, and their use also might reduce progression of HIV by suppressing immune activation. We examined the effect that prednisolone has on survival in HIV-1-associated pleural tuberculosis.\n We conducted a randomized, double-blind, placebo-controlled trial of prednisolone as an adjunct to tuberculosis treatment, in adults with HIV-1-associated pleural tuberculosis. The primary outcome was death. Analysis was by intention to treat.\n Of 197 participants, 99 were assigned to the prednisolone group and 98 to the placebo group. The mortality rate was 21 deaths/100 person-years (pyr) in the prednisolone group and 25 deaths/100 pyr in the placebo group (age-, sex-, and initial CD4+ T cell count-adjusted mortality rate ratio, 0.99 [95% confidence interval, 0.62-1.56] [P =.95]). Resolution of tuberculosis was faster in the prednisolone group, but recurrence rates were slightly (though not significantly) higher, and use of prednisolone was associated with a significantly higher incidence of Kaposi sarcoma (4.2 cases/100 pyr, compared with 0 cases/100 pyr [P =.02]).\n In view of the lack of survival benefit and the increased risk of Kaposi sarcoma, the use of prednisolone in HIV-associated tuberculous pleurisy is not recommended.",
"Pneumocystis carinii pneumonia remains a common cause of serious morbidity and mortality in patients with the acquired immunodeficiency syndrome (AIDS). The extensive lung injury that accompanies pneumocystis-associated respiratory failure and the reports of clinical benefit from the use of adjunctive corticosteroids provided the rationale for this prospective multicenter trial.\n A total of 333 patients with AIDS and pneumocystis pneumonia received standard treatment and were randomly assigned to receive either corticosteroids (beginning with the equivalent of 40 mg of prednisone twice daily) or no additional therapy. The primary end points in this unblinded trial were the occurrence of respiratory failure (hypoxemia ratio [partial pressure of arterial oxygen divided by fraction of inspired oxygen] less than 75, intubation, or death), death, and dose-limiting toxicity of the initial standard therapy.\n Of the patients with confirmed or presumed pneumocystis pneumonia (n = 225 and n = 26, respectively), those assigned to treatment with corticosteroids had a lower cumulative risk at 31 days of respiratory failure (0.14 vs. 0.30, P = 0.004) and of death (0.11 vs. 0.23, P = 0.009), as well as a lower risk of death within 84 days (0.16 vs. 0.26, P = 0.026). The frequency of dose-limiting toxicity of the standard therapy was similar in the two treatment groups. Intention-to-treat analyses of the entire cohort confirmed these findings. Clinical benefit could not be demonstrated, however, for patients with mild disease (hypoxemia ratio, greater than 350), equivalent to a partial pressure of oxygen greater than 75 torr on room air. The patients assigned to corticosteroid treatment had an excess of localized herpetic lesions (26 percent vs. 15 percent, P = 0.04) but not of other infections or of neoplasms.\n Early adjunctive treatment with corticosteroids reduces the risks of respiratory failure and death in patients with AIDS and moderate-to-severe pneumocystis pneumonia. Because the adverse effects are few, corticosteroids should be included as part of the initial treatment for persons with AIDS who have moderate-to-severe pneumocystis pneumonia.",
"Fifty-nine human immunodeficiency virus type-1-infected patients with a microscopically proven first episode of moderate to severe Pneumocystis carinii pneumonia (PCP) were enrolled into a randomized European multicenter study. The effect of adjunctive corticosteroid (CS) therapy was assessed on (a) survival to discharge, (b) need for mechanical ventilation, and (c) survival at day 90. CS was given within 24 h of standard therapy as intravenous methylprednisolone 2 mg/kg body weight daily for 10 days. All patients received cotrimoxazole as standard treatment. Inclusion criteria were a PaO2 less than 9.0 kPa (67.5 mm Hg) and/or a PaCO2 less than 4.0 kPa (30.0 mm Hg) while breathing room air. During the acute episode of PCP, 9 (31%) of the 29 control patients died versus 3 (10%) of the 30 CS patients; p = 0.01. Mechanical ventilation was necessary in 15 patients; 12 (41%) in the control group and 3 (10%) in the CS group; p = 0.01. The 90-day survival was 69% in controls versus 87% in CS patients; p = 0.07. Based on these data we conclude that adjunctive CS therapy for moderate to severe PCP in AIDS patients reduces the acute mortality and the need for mechanical ventilation."
] |
There are insufficient data to support evidence-based recommendations regarding the use of adjunctive corticosteroids in people with tuberculous pleurisy. Randomized controlled trials that are sufficiently powered to evaluate the effects of corticosteroids on both morbidity and mortality are needed. The effects of corticosteroids on HIV-related complications, such as Kaposi sarcoma, should be assessed in people co-infected with HIV.
|
CD000184
|
[
"15842288",
"2692178",
"19087079",
"15617697",
"1998637",
"8602315",
"9916961",
"9492717",
"6743606",
"8906005",
"19701035",
"11914565",
"8885736",
"15842277",
"19682886",
"8336880",
"6342657",
"16234141",
"11209625",
"11006204",
"9819872",
"1530035"
] |
[
"Tocolysis for repeat external cephalic version in breech presentation at term: a randomised, double-blinded, placebo-controlled trial.",
"A prospective randomised controlled trial of external cephalic version comparing two methods of uterine tocolysis with a non-tocolysis group.",
"Oral nifepidine versus subcutaneous terbutaline tocolysis for external cephalic version: a double-blind randomised trial.",
"Tocolysis in term breech external cephalic version.",
"External cephalic version at term. A randomized controlled trial using tocolysis.",
"A double-blind randomized comparison of lidocaine and saline for cervical anesthesia.",
"Randomized comparison of intravenous nitroglycerin and magnesium sulfate for treatment of preterm labor.",
"Extraamniotic saline infusion is promising in preparing the cervix for induction of labor.",
"A randomized trial of external cephalic version with tocolysis in late pregnancy.",
"A randomized, double blind, controlled trial of tocolysis to assist external cephalic version in late pregnancy.",
"Intravenous nitroglycerin for external cephalic version: a randomized controlled trial.",
"Influence of volume preloading on uteroplacental and fetal circulation during spinal anaesthesia for caesarean section in uncomplicated singleton pregnancies.",
"Does the use of a tocolytic agent affect the success rate of external cephalic version?",
"A randomised controlled trial of biopsy forceps and cannula aspiration for transcervical chorionic villus sampling.",
"A randomized controlled trial of the effect of combined spinal-epidural analgesia on the success of external cephalic version for breech presentation.",
"A randomized trial of extra-amniotic saline infusion plus intracervical Foley catheter balloon versus prostaglandin E2 vaginal gel for ripening the cervix and inducing labor in patients with unfavorable cervices.",
"Effect of external cephalic version in late pregnancy on breech presentation and caesarean section rate: a controlled trial.",
"Randomised trial of intravaginal misoprostol and intracervical Foley catheter for cervical ripening and induction of labour.",
"Preinduction cervical ripening techniques compared.",
"Chemical ripening of the cervix with intracervical application of sodium nitroprusside: a randomized controlled trial.",
"The efficacy and fetal-maternal cardiovascular effects of transdermal glyceryl trinitrate in the prophylaxis of pre-eclampsia and its complications: a randomized double-blind placebo-controlled trial.",
"Evaluation of maternal fluid dynamics during tocolytic therapy with ritodrine hydrochloride and magnesium sulfate."
] |
[
"External cephalic version (ECV) reduces the incidence of breech presentation at term and caesarean section for non-cephalic births. Tocolytics may improve success rates, but are time consuming, may cause side effects and have not been proven to alter caesarean section rates. The aim of this trial was to determine whether tocolysis should be used if ECV is being re-attempted after a failed attempt.\n To determine whether tocolysis should be used if ECV is being re-attempted after a failed attempt.\n Randomised, double-blinded, placebo-controlled trial.\n UK teaching hospital.\n One hundred and twenty-four women with a breech presentation at term who had undergone an unsuccessful attempt at ECV.\n Relative risks with 95% confidence intervals for categorical variables and a t test for continuous variables. Analysis was by intention to treat.\n Incidence of cephalic presentation at delivery. Secondary outcomes were caesarean section and measures of neonatal and maternal morbidity.\n The use of tocolysis for a repeat attempt at ECV significantly increases the incidence of cephalic presentation at delivery (RR 3.21; 95% CI 1.23-8.39) and reduces the incidence of caesarean section (RR 0.33; 95% CI 0.14-0.80). The effects were most marked in multiparous women (RR for cephalic presentation at delivery 9.38; 95% CI 1.64-53.62). Maternal and neonatal morbidity remain unchanged.\n The use of tocolysis increases the success rate of repeat ECV and reduces the incidence of caesarean section. A policy of only using tocolysis where an initial attempt has failed leads to a relatively high success rate with minimum usage of tocolysis.",
"The use of tocolvtic agents to enhance uterine relaxation and facilitate external cephalic version (ECV) has come under recent debate. We studied 90 breech presentations in late pregnancy who did not have contra-indications to ECV. The patients were randomised into 3 groups of 30 patients each: one was administered oral salbutamol 4 mg t.d.s.; another had intravenous salbutamol infused until the maternal heart rate rose above 100 bpm for 30 mins; and the last served as a control group. All patients in each group were matched for parity and gestation, and each had an intravenous line, thereby masking the treatment group from the 2 doctors who performed half the number of ECVs each. There was no significant difference in the success of ECV between the treatment and control groups (46.6% vs 50.0% vs 46.6%). The gestational age, the placental site, the attitude of the breech, the abdominal girth, and the maternal weight and fetal birth weights did not seem to influence results. On the other hand, there was a significant difference in successful ECV between nullipara (26%) and multipara (75%) (p less than 0.001). There were no cases of abruptio placenta or foetal distress, and one patient entered labour one day after the ECV at 39 weeks gestation. There were 2 cases of spontaneous version after failed ECV, and one case of spontaneous reversion to breech after successful ECV. We conclude that the use of salbutamol does not increase the incidence of successful ECV, but multiparity predicts for a successful outcome.",
"To evaluate oral nifedipine versus subcutaneous terbutaline tocolysis for external cephalic version (ECV).\n A double-blind randomised trial.\n A university hospital in Malaysia.\n Non-labouring women with a term singleton fetus in breech presentation or transverse lie suitable for elective ECV.\n Participants were randomised to either 10 mg oral nifedipine tablet and subcutaneous saline placebo or oral placebo tablet and 250 microgram bolus terbutaline subcutaneously. Participants and providers were blinded. Ultrasound assessment and cardiotocogram were performed prior to ECV. ECV was commenced 20-30 minutes after treatment. A maximum of two ECV attempts were permitted. Elective caesarean delivery or a repeat ECV attempt at a later date was offered to participants following failed ECV. After successful ECV, management was expectant.\n Primary outcomes were successful ECV (cephalic presentation immediately after ECV) and caesarean delivery.\n Ninety women were randomised: 44 to nifedipine and 46 to terbutaline. Initial ECV success rate was 15/44 (34.1%) versus 24/46 (52.2%) (relative risk [RR] 0.7, 95% CI 0.4-1.1; P= 0.094), and caesarean delivery rate was 34/44 (77.3%) versus 26/46 (56.5%) (RR 1.4, 95% CI 1.01-1.85; numbers needed to treat to benefit 5, 95% CI 2.5-55; P= 0.046) for nifedipine and terbutaline groups, respectively. Neonatal outcome was not different.\n Bolus subcutaneous terbutaline tocolysis for ECV compared with oral nifedipine resulted in less caesarean deliveries. ECV success rate was not significantly higher. Larger studies are indicated.",
"To study the effect of ritodrine tocolysis on the success of external cephalic version (ECV) and to assess the role of ECV in breech presentation at our centre.\n A prospective randomized double-blind-controlled trial comparing ritodrine and placebo in ECV of singleton term breech pregnancy at a tertiary hospital.\n Among the 60 patients who were recruited, there was a success rate of 36.7%. Ritodrine tocolysis significantly improved the success rate of ECV (50% vs. 23%; P=0.032). There was a marked effect of ritodrine tocolysis on the ECV success in nulliparae (36.4% vs. 13.0%) and multiparae (87.5% vs. 57.1%). External cephalic version has shown to reduce the rate of cesarean section for breech presentation by 33.5% in our unit.\n External cephalic version significantly reduced the rate of cesarean section in breech presentation, and ritodrine tocolysis improved the success of ECV and should be offered to both nulliparous and parous women in the case of term breech presentation.",
"To assess the role of external cephalic version (ECV) at term, using tocolysis.\n A randomized controlled trial over a 12 month period.\n Harare Maternity Hospital, Harare, Zimbabwe.\n 208 women with breech presentation at term were recruited after satisfying eligibility criteria. There were 103 women in the study group and 105 in the control group. At the end of the study a further 104 women were recruited for ECV.\n ECV attempted after intravenous injection of 10 micrograms of hexaprenaline, using either forward or backward somersault over a maximum period of 5 min.\n Success rate in terms of presentation during labour, need for caesarean section, and various variables related to fetal outcome.\n ECV reduced the frequency of breech presentation during labour from 83% to 17% and that of caesarean section from 33% to 13%. There were no troublesome complications from the procedure.\n In carefully selected women with breech presentation, ECV at term using tocolysis, safely reduced the rate of breech presentation in labour and also the caesarean section rate. Further research is needed to determine the role of ECV in early labour.",
"To compare bacteriostatic saline and buffered lidocaine for cervical anesthesia to blunt the reported pain during brief suction curettage.\n A double-blind randomized clinical trial was conducted on women presenting for pregnancy termination procedures. Participants received either paracervical submucosal injections of bacteriostatic saline or 1% buffered lidocaine just before cervical dilation. Self-reported pain intensity was assessed at three time points during and 30 minutes after the procedure.\n Fifty-two of 135 eligible women presenting for pregnancy termination procedures participated in the study. Pain intensity ratings in lidocaine and saline treatment subjects did not differ significantly at any point. Our study had a power of 0.94 to detect more than a 15% difference on the 21-point box scale between the two solutions. Only one patient requested her block be repeated, and she had received lidocaine originally. Furthermore, of those women receiving lidocaine, 11% reported mild toxicity symptoms.\n To minimize lidocaine toxicity for a brief suction curettage procedure, bacteriostatic saline or very dilute lidocaine could be considered for the paracervical injection solution. The local anesthetic mechanism may be distention rather than blockage of specific autonomic nerves when there is no waiting period. This would mean that the term paracervical block could be changed to cervical anesthesia.",
"To compare the safety and efficacy of high-dose intravenous (IV) nitroglycerin with those of IV magnesium sulfate for acute tocolysis of preterm labor.\n Thirty-one women with preterm labor before 35 weeks' gestation were assigned randomly to IV magnesium sulfate or IV nitroglycerin for tocolysis. Preterm labor was defined as the occurrence of at least two contractions in 10 minutes, with cervical change or ruptured membranes. Acute tocolysis was defined as tocolysis for up to 48 hours. Magnesium sulfate was administered as a 4-g bolus, then at a rate of 2-4 g/h. Nitroglycerin was administered as a 100-microg bolus, then at a rate of 1- to 10-microg/kg/min. The primary outcome measure was achievement of at least 12 hours of successful tocolysis.\n Thirty patients were available for analysis. There were no significant differences in gestational age, cervical dilation, or incidence of ruptured membranes between groups at the initiation of tocolysis. Successful tocolysis was achieved in six of 16 patients receiving nitroglycerin, compared with 11 of 14 receiving magnesium sulfate (37.5 versus 78.6%, P = .033). Tocolytic failures (nitroglycerin versus magnesium sulfate) were due to persistent contractions with cervical change or rupture of previously intact membranes (five of 16 versus two of 14), persistent hypotension (four of 16 versus none of 14), and other severe side effects (one of 16 versus one of 14). Maternal hemodynamic alterations were more pronounced in patients who received nitroglycerin, and 25% of patients assigned to nitroglycerin treatment had hypotension requiring discontinuation of therapy.\n Tocolytic failures were more common with nitroglycerin than with magnesium sulfate. The hemodynamic alterations noted in patients receiving nitroglycerin, including a 25% incidence of persistent hypotension, might limit the usefulness of IV nitroglycerin for the acute tocolysis of preterm labor.",
"The application of local prostaglandins before induction of labor in women with an unripe cervix is standard procedure in Sweden. Side effects include uterine hypertonus and occasionally fetal heart rate abnormalities. Failed ripening is reported in up to 25% of cases. A previous report of ripening of the cervix by use of extraamniotic physiologic saline infusion through a Foley catheter applied in the cervix claimed results superior to topical prostaglandins.\n To conduct a prospective randomized trial of extraamniotic saline infusion and intracervical application of dinoprost 0.5 mg on cervical ripening and outcome of labor.\n Eighty-five term singleton pregnant women with unripe cervices where induction of labor was indicated were randomized to prostaglandin or saline infusion after obtaining informed consent. Outcome variables were improvement of cervical score, induction delivery time and mode of delivery.\n The 42 women in the saline infusion group obtained significantly (p < or = 0.001) higher cervical scores and shorter induction delivery intervals (p < or = 0.005) than the 43 women in the prostaglandin group. Cases of unripe cervix after 24 hours were significantly (p < or = 0.01) fewer in the saline group. There were more Cesarean sections in the saline group, but this difference was not significant. Saline infusion did not induce uterine activity and oxytocin was given in every case after the expulsion of the catheter.\n In this study extraamniotic saline infusion was a more efficacious method for ripening of the cervix than intracervical prostaglandin. The absence of early painful contractions is an advantage, but effective stimulation of labor is required to effect delivery after maturation of the cervix.",
"The effect of external version under tocolysis with intravenous ritodrine during the 37th week of gestation was studied in a prospective randomized trial comprising 130 consecutive women with a fetus in breech presentation. Version was successful in 41% of the patients, all of whom had a cephalic vaginal delivery. Of the 56 women in the control group in whom version was not attempted; 8 (14%) converted to the vertex presentation spontaneously. Failure of version was significantly correlated with primiparity, location of the placenta on the anterior uterine wall, and maternal weight. The caesarean section rate was significantly lower in the version group (27%) than in the control group (46%) (P less than 0.05). The overall caesarean section rate for a fetus in breech presentation was 50%. There were no serious complications associated with version and the condition of the infants at birth was better in the version group than in the control group. We advise external version under tocolysis in late pregnancy to reduce the frequency of breech presentation in labour.",
"External cephalic version at term is not always successful. This trial was done to ascertain whether tocolysis has any effect on the success rate.\n A randomized, double blind, controlled trial, with continuous paired sequential analysis. Fifty-one consecutive patients with a singleton fetus in a breech presentation between 36 and 38 weeks gestation, external version being attempted on each. Ritodrine infusion or placebo was infused before attempt at external cephalic version.\n A university teaching hospital with 8000 confinements annually.\n Version was successful in 17 of the 25 patients given tocolysis, but in only eight of the 25 given placebo (p < 0.01). A positive benefit for tocolysis was shown after version had been completed in 10 pairs of patients. However the trial was continued until 25 pairs had been analyzed. The benefit deteriorated during analysis of the last 15 pairs suggesting that the initial benefit may reflect a learning curve for the procedure.\n Tocolysis is likely to improve the success rate of external cephalic version in late pregnancy, especially in nulliparous mothers or where doctors are learning the technique.",
"To estimate whether treatment with intravenous nitroglycerin for uterine relaxation increases the chance of successful external cephalic version.\n Two double-blind, randomized clinical trials were undertaken: one in nulliparous women and a second in multiparous women. Women presenting for external cephalic version at term were eligible to participate. The primary outcome was immediate success of external cephalic version. Other outcomes were presentation at delivery, cesarean delivery rate, and side effects and complications. Sample size calculations were based on a 100% increase in success of external cephalic version with a one-sided analysis and alpha=0.05 (80% power).\n In total, 126 women were recruited-82 in the nulliparous trial and 44 in the multiparous trial. Seven patients did not have external cephalic version before delivery but were included in the analysis of success of external cephalic version. One patient was lost to follow-up. The external cephalic version success rate for nulliparous patients was 24% (10 of 42) in patients who received nitroglycerin compared with 8% (3 of 40) in those who receive placebo (P=.04, one-sided Fisher exact test, odds ratio 3.85, lower bound 1.22). In multiparous patients, the external cephalic version success rate did not differ significantly between groups: 44% (10 of 23) in the nitroglycerin group compared with 43% (9 of 21) in the placebo group (P=.60).\n Treatment with intravenous nitroglycerin increased the rate of successful external cephalic version in nulliparous, but not in multiparous, women. Treatment with intravenous nitroglycerin appeared to be safe, but our numbers were too small to rule out rare serious adverse effects.\n I.",
"Effects of volume preloading during spinal anaesthesia for elective caesarean section on maternal blood pressure, feto-maternal circulation and fetal outcome.\n In a pilot study a randomised trial was performed in 22 healthy women with uncomplicated, singleton pregnancies at 36-40 weeks of gestation undergoing elective caesarean section under spinal anaesthesia. In the low volume group (group A) patients received 150 ml of crystalloid solution for preloading, in the high volume group (group B) they were given 15 ml/kg of crystalloid solution for preloading before the initiation of spinal anaesthesia. Maternal blood pressure was monitored intermittently. Hypotension was defined as a decrease in systolic pressure to less than 80% of the baseline value. The Doppler flow evaluation consisted of measurements from the uterine artery at the placental site, fetal umbilical artery and fetal middle cerebral artery. Pulsatility indices were derived before and after fluid preloading, and when spinal anaesthesia was established. The neonatal outcome was assessed by Apgar scores, arterial acid base status and neurologic and adaptive capacity scores (NACS).\n The incidence of maternal hypotension in both groups was 45.5% (n = 10); 3 cases occurred in group A compared to 7 cases in group B (n.s.). There was no evidence that the high dose volume is useful in preventing maternal hypotension. The pulsatility indices of uterine arteries, umbilical arteries and middle cerebral arteries were not altered. Statistical analysis showed no changes in neonatal outcome concerning umbilical arterial pH, Apgar score and NACS (n.s.) between groups A and B.\n Our preliminary results suggest that high dose crystalloid volume preloading has no preventive function in the avoidance of maternal hypotension in healthy parturients undergoing elective caesarean section under spinal anaesthesia, and shows no harmful effects on neonatal outcome as long as maternal hypotension is corrected immediately. However, the statistical significance may reflect the small sample size, and larger series are needed before changing the current management.\n Copyright 2002 S. Karger AG, Basel",
"Our purpose was to study the effect of ritodrine tocolysis on the success rate of external cephalic version at > or = 36 weeks' gestation.\n This was a prospective, double-blinded, randomized study. All patients were > or = 36 weeks' gestation, confirmed by early ultrasonography. External cephalic version assessment included nonstress testing before and after external cephalic version and ultrasonographic evaluation of type of breech, estimated fetal weight, position of placenta and fetal spine, and amniotic fluid index. Patients were excluded if the breech was not mobile or if they had any contraindications to tocolysis or external cephalic version. After randomization 283 patients received either ritodrine (111 micrograms/min) or identical placebo by intravenous infusion for > or = 20 minutes. Up to three attempts at external cephalic version under ultrasonographic surveillance were performed. With an alpha error of 0.05 and a beta of 0.2, 264 patients were required to complete this study.\n There were no differences between study groups in maternal age, body mass index, gestational age, amniotic fluid index, position of fetal spine, and placental location. Statistical analysis controlled for parity because parity had a major influence on success rates. There was a higher success rate in the group receiving ritodrine tocolysis (52% vs 42%, p = 0.028). Ritodrine improved success rates in nulliparous patients (43% vs 25%, p = 0.026) but not in parous subjects (66% vs 58%, p = 0.385).\n Ritodrine tocolysis improves the success rate of external cephalic version performed at > or = 36 weeks in nulliparous patients.",
"This trial compared two instruments for transcervical chorionic villus sampling (CVS).\n Randomised controlled trial.\n Regional university prenatal diagnosis and treatment centre.\n Two hundred women were randomised at 10(+0)-12(+6) weeks of gestation to transcervical CVS using cannula aspiration (CA) or biopsy forceps (BF).\n Women undergoing indicated CVS signed informed consent. Randomisation after decision to perform transcervical CVS.\n Primary outcome: the rise in maternal serum alpha-fetoprotein (alpha-FP). Secondary outcomes: (i) placental trauma (fetomaternal haemorrhage [FMH]); (ii) laboratory, procedure, and cytogenetic results and pregnancy outcomes; (iii) patient and operator satisfaction; and (iv) economic analyses. Analyses were performed by intention to treat.\n The -FP rise did not differ between groups; there was no other evidence of placental trauma. BF were better tolerated by women, provided culturable tissue, after fewer instrument passes, with greater ease and in less time. BF were associated with cost savings.\n Unlike -FP, other markers of FMH were unaltered, questioning the reliability of alpha-FP as an indicator of FMH. Compared with CA, transcervical BF caused comparable placental trauma, appeared to be similarly effective and safe and were preferred by operators and patients.",
"Improving the success of external cephalic version (ECV) for breech presentation may help avoid some cesarean deliveries. The results of randomized trials comparing the success of ECV with neuraxial analgesia compared to control are inconsistent. We hypothesized that combined spinal-epidural (CSE) analgesia would increase the success of ECV when compared with systemic opioid analgesia.\n Parturients with singleton breech presentation (n=96) were randomized to receive CSE analgesia with bupivacaine 2.5mg and fentanyl 15 microg (CSE group) or intravenous fentanyl 50 microg (SYS group) before ECV attempt. The primary outcome was ECV success.\n The success rate of ECV was 47% with CSE and 31% in the SYS group (P=0.14). Subsequent vaginal delivery was 36% for CSE and 25% for SYS (P=0.27). Median [IQR] visual analog pain scores (0-100mm scale) were lower with CSE (3 [0-12]) compared to SYS analgesia (36 [16 to 54]) (P<0.005) and patient satisfaction (0-10 scale) was higher (CSE 10 [9 to 10] versus SYS 7 [4 to 9]) (P<0.005). There were no differences in fetal heart rate patterns, but median time to return to fetal heart rate reactivity after analgesia was shorter with CSE (13 [IQR 9-21] min) compared to the SYS group (39 [IQR 23-51] min) (P=0.02).\n There was no difference in the rate of successful ECV or vaginal delivery with CSE compared to intravenous fentanyl analgesia. Pain scores were lower and satisfaction higher with CSE analgesia, and median time to fetal heart rate reactivity was shorter in the CSE group.",
"To compare the efficacy of extra-amniotic saline solution infusion plus an intracervical Foley catheter balloon versus 2.85 mg prostaglandin (PG) E2 vaginal gel in ripening the cervix, inducing labor, and achieving vaginal delivery in patients at term with an unfavorable cervix.\n A randomized study of the two methods was performed in 112 patients with a Bishop score of 5 or less.\n Extra-amniotic saline infusion plus intracervical Foley catheter balloon was more effective than PGE2 vaginal gel in causing cervical ripening (relative risk [RR] 2.5965, 95% confidence interval [CI] 1.7277-3.9022, exact two-tailed P = .000001) and in inducing labor (RR 4.3333, 95% CI 1.7223-10.9026, exact two-tailed P = .0000181). However, the final delivery outcome was an equally high number of cesarean deliveries (26 of 56, or 46.4%) for both methods. Maternal and neonatal complications were minimal and not significantly different.\n Extra-amniotic saline infusion with a Foley catheter was more effective than 2.85 mg PGE2 vaginal gel in ripening the cervix and inducing labor. These advantages did not translate into a large number of vaginal deliveries, indicating that factors other than cervical ripening may be responsible for the high incidence of cesarean in patients with an unfavorable cervix.",
"A prospective randomized controlled trial of external cephalic version (ECV) in late pregnancy is reported. All pregnancies were assessed with ultrasound and cardiotocography. ECV was successful in 29 out of 30 patients (97%). Breech presentation at delivery occurred in 67% of the control group and in 3% of the ECV group. The caesarean section rates were 43 and 20% respectively. Tocolysis was used in seven patients. A new technique of ECV with the steep lateral position is described. Complications were limited to cardiotocographic changes and one patient with unexplained vaginal spotting. The procedure is recommended provided appropriate patient selection and surveillance is practised.",
"Induction of labour may be indicated despite an unripe cervix. The purpose of this study was to compare the safety and efficacy of intravaginal misoprostol and an intracervical Foley's balloon catheter for preinduction cervical ripening and labour induction. A total of 120 patients requiring indicated induction of labour with an unfavourable cervix (Bishop's score < or =4) were randomised prospectively to receive either 50 mug intravaginal misoprostol every 6 h for a maximum of two doses, or an intracervical Foley balloon catheter for 12 h followed by an intravenous oxytocin infusion. The two arms of the study were comparable with respect to maternal age, parity, gestational age, indication for induction, and initial Bishop's scores. There were significant change in the Bishop's score in the two groups (5.9 +/- 0.2 and 4.0 +/- 0.2, respectively, p < 0.001) but no inter group differences. Oxytocin induction or augmentation of labour occurred more in the catheter group (95%) than in the misoprostol group (43.3%) (p < 0.0001). Induction to delivery interval was significantly shorter in the misoprostol group than in the catheter group (8.7 +/- 2.4 vs 11.9 +/- 2.7 h p < 0.0001). There was no significant difference noted in the caesarean or other operative delivery rates among patients in the two treatment groups. There was a higher incidence of tachysystole and hyperstimulation in the misoprostol group than in the catheter group (p < 0.03). No differences were observed between groups for meconium passage, 1- or 5-min Apgar scores < 7 and admission into the neonatal intensive care unit. In conclusion, the maternal and perinatal outcomes in this study have shown no difference confirming the efficacy and safety of both methods, however we observe a decrease in the induction-to-delivery interval when misoprostol is used for this purpose.",
"To assess the clinical efficacy of pharmacologic, mechanical and combination techniques of cervical ripening.\n From March 1997 to August 1998, all cervical-ripening patients at Lehigh Valley Hospital were randomly assigned to three groups: intravaginal misoprostol, intracervical Foley catheter, or combination prostaglandin E2 (PGE2) gel and Foley catheter. Inclusion criteria included Bishop score < or = 5 and no contraindication to labor. The remaining delivery process was actively managed according to established guidelines. Multiple variables in perinatal outcome were analyzed, with the cesarean section rate and time from ripening to delivery as the main outcome variables.\n Of the 205 patients, 65 were randomized to the misoprostol group, 71 to the Foley group and 69 to the catheter-and-gel group. There were no differences between groups in delivery indications, maternal demographics, ultrasound findings, labor interventions, intrapartum times, mode of delivery, postpartum complications or neonatal outcomes. The misoprostol group demonstrated a higher rate of uterine tachysystole and required oxytocin less when compared to the two catheter groups.\n The higher rate of uterine tachysystole with misoprostol did not increase the cesarean section rate. The higher rate of oxytocin required by the two catheter groups did not increase the delivery time intervals. There appears to be no benefit to adding intracervical or intravaginal PGE2 gel to the intracervical Foley balloon. The misoprostol and catheter ripening techniques have similar safety and efficacy.",
"Nitric oxide (NO) has been found to be involved in the processes of cervical ripening. In a randomized, placebo-controlled study, cervical softening by an intracervical application of sodium nitroprusside, one of the most clinically potent and effective NO donor agents, was evaluated. A total of 36 primigravid women undergoing pregnancy termination between 9 and 12.5 weeks were enrolled. In one series, 18 patients were randomized to receive intracervically either placebo or 1% nitroprusside gel (5 mg), followed by uterine evacuation 6 h after treatment. In another series, 18 patients received either placebo or 2% nitroprusside gel (10 mg) into the cervical canal followed by uterine evacuation 3 h later. The cervical resistance, i.e. the force required to dilate the cervix from 3 to 10 mm, was the main outcome variable. It was recorded using a force sensing apparatus (dynamometer). Blood pressure was measured. Adverse events were recorded until 2 h after surgery. Women treated with both doses of nitroprusside gel showed values of cervical resistance significantly lower than those treated with placebo gel, at any tested diameter. No differences were found between subjects treated with the two different doses of nitroprusside. No significant consistent changes in blood pressure were induced by either dose of nitroprusside. No headaches were found in subjects treated with the NO donor. This study demonstrates that sodium nitroprusside applied into the cervical canal induces a rapid and significant softening of the cervix, thus reducing the force required to dilate it, compared with placebo-treated subjects. The chemical ripening of the cervix with sodium nitroprusside intracervical gel is an efficacious procedure in first-trimester pregnancy.",
"Pre-eclampsia continues to be a major cause of maternal and perinatal mortality. A disorder of the nitric oxide system is implicated in the pathogenesis of this condition and preliminary studies have suggested a possible therapeutic role for nitric oxide donors in women with established pre-eclampsia. The aim of this study was to determine whether pre-eclampsia and its complications could be prevented by the long-term use of nitric oxide donors in a group of women identified to be at risk on the basis of abnormal uterine artery Doppler measurements.\n We enrolled 40 healthy normotensive women at high risk of pre-eclampsia selected on the basis of abnormal uterine artery Doppler waveforms at 24-26 weeks of gestation. Women were randomly allocated to receive transdermal glyceryl trinitrate 5 mg-patches or equivalent placebo patches in a double-blind randomized study. The primary outcome measures were pre-eclampsia, fetal growth restriction, preterm delivery or small for gestational age/fetal growth restriction rates. Patches were worn daily from recruitment for 10 weeks or until delivery.\n The primary outcomes were not significantly different in the placebo compared to the glyceryl trinitrate group. However, survival analysis of adverse events with gestation in both groups showed a significantly reduced risk of an adverse event in the glyceryl trinitrate group (p = 0.004), equating to a 73% reduction in hazard. There was no difference in maternal systolic and diastolic blood pressure, mean uterine artery resistance index and fetal umbilical and middle cerebral artery pulsatility indices between the groups.\n Low-dose prophylactic transdermal glyceryl trinitrate commenced late in the second trimester did not reduce the incidence of pre-eclampsia, preterm delivery or fetal growth restriction, but may increase the likelihood of a complication-free pregnancy. Transdermal glyceryl trinitrate (5 mg/day) did not affect maternal cardiovascular, uterine artery or fetal arterial Doppler parameters.",
"The purpose of the study was to observe and compare the effects of ritodrine hydrochloride and magnesium sulfate on maternal fluid dynamics.\n Fourteen women in preterm labor were prospectively studied during tocolytic therapy with either ritodrine hydrochloride or magnesium sulfate. The cardiovascular and renal effects of a pretreatment crystalloid infusion were compared with those observed during tocolytic therapy. Profile analysis and repeated measures of variance were used to analyze the data.\n Ritodrine hydrochloride was associated with decreased colloid osmotic pressure, hematocrit, and serum proteins and increased maternal and fetal heart rates. Arginine vasopressin levels increased during the first 2 hours of therapy, then returned to baseline. Sodium excretion was reduced and there was marked fluid retention. Intravenous magnesium sulfate also resulted in a reduction of colloid osmotic pressure, but hematocrit, serum protein concentration, arginine vasopressin, maternal and fetal heart rates, and mean arterial pressure were minimally affected. Sodium excretion increased to a maximum at 6 to 8 hours of treatment, then returned to baseline. A positive fluid balance was also noted in magnesium sulfate-treated patients but to a lesser degree than with ritodrine.\n Sodium retention appears to be the primary cause of plasma volume expansion in ritodrine-treated patients, whereas volume expansion during magnesium sulfate therapy is probably related to intravenous overhydration. In the absence of risk factors for pulmonary capillary membrane injury, available evidence supports volume overload as the principal mechanism for pulmonary edema during tocolytic therapy."
] |
Betastimulants, to facilitate ECV, increased cephalic presentation in labour and birth, and reduced the caesarean section rate in both nulliparous and multiparous women, but there were insufficient data on adverse effects. Calcium channel blockers and nitric acid donors had insufficient data to provide good evidence. At present we recommend betamimetics for facilitating ECV.
There is scope for further research. The possible benefits of tocolysis to reduce the force required for successful version and the possible risks of maternal cardiovascular side effects, need to be addressed further. Further trials are needed to compare the effectiveness of routine versus selective use of tocolysis, the role of regional analgesia, fetal acoustic stimulation, amnioinfusion and the effect of intravenous or oral hydration prior to ECV.
Although randomised trials of nitroglycerine are small, the results are sufficiently negative to discourage further trials.
|
CD005979
|
[
"12187178",
"11944760",
"14534526",
"11242426",
"12126319",
"11760489",
"16174135"
] |
[
"Health services utilization with reference drug pricing of histamine(2) receptor antagonists in British Columbia elderly.",
"Impact of reference-based pricing for angiotensin-converting enzyme inhibitors on drug utilization.",
"Clinical and economic consequences of reference pricing for dihydropyridine calcium channel blockers.",
"Adverse events associated with prescription drug cost-sharing among poor and elderly persons.",
"Impact of reference-based pricing for histamine-2 receptor antagonists and restricted access for proton pump inhibitors in British Columbia.",
"Impact of the Minimum Pricing Policy and introduction of brand (generic) substitution into the Pharmaceutical Benefits Scheme in Australia.",
"The impact of reference pricing of nonsteroidal anti-inflammatory agents on the use and costs of analgesic drugs."
] |
[
"In October 1995, British Columbia introduced a reference pricing policy for five therapeutic classes of drugs, including histamine(2) receptor antagonists (H(2)RAs), for beneficiaries of its prescription drug program, Pharmacare.\n To evaluate utilization trends in consumption of health services in a cohort of Pharmacare beneficiaries to determine if a worsening of health outcomes could be detected after implementation of the reference pricing policy.\n Two cohorts, \"control\" (21 months before the reference pricing policy) and \"exposed\" (at risk for policy effects), were followed for 21 months. Using a longitudinal generalized linear model (Poisson), and controlling for age, sex, and prescriptions in unique drug classes, trend lines in each of these time series were compared for 3 periods: 9 months before policy implementation (or corresponding index date in the control cohort), 6 months after policy implementation, and a subsequent 6-month period.\n Two cohorts, each of size 10,000, were constructed by randomly sampling the population of Pharmacare beneficiaries exposed to H(2)RAs and other antisecretory drugs for 1993 through 1996.\n Prescriptions, physician office visits and associated transactions (ie, laboratory tests), emergency room visits, hospitalizations, hospital length of stay, and vital statistics.\n Differences between periods and between cohorts for health services utilization were not significant or decreased after imposition of the reference pricing policy.\n For these measures, there has been no worsening of health outcomes associated with implementing the reference pricing policy.",
"Increasing copayments for higher-priced prescription medications has been suggested as a means to help finance drug coverage for elderly patients, but evaluations of the impact of such policies are rare. The objective of this study was to analyze the effect of reference-based pricing of angiotensin-converting enzyme (ACE) inhibitors on drug utilization, cost savings and potential substitution with other medication classes.\n We analyzed 36 months of claims data from British Columbia for 2 years before and 1 year after implementation of reference-based pricing (in January 1997). The 119,074 patients were community-living Pharmacare beneficiaries 65 years of age or older who used ACE inhibitors during the study period. The main outcomes were changes over time in use of ACE inhibitors, use of antihypertensive drugs and expenditures for antihypertensive drugs, as well as predictors of medication switching related to reference-based pricing.\n We observed a sharp decline (29%) in the use of higher-priced cost-shared ACE inhibitors immediately after implementation of the policy (p < 0.001). After a transition period, the post-implementation utilization rate for all ACE inhibitors was 11% lower than projected from pre-implementation data. However, overall utilization of antihypertensives was unchanged (p = 0.40). The policy saved $6.7 million in pharmaceutical expenditures during its first 12 months. Patients with heart failure or diabetes mellitus who were taking a cost-shared ACE inhibitor were more likely to remain on the same medication after implementation of reference-based pricing (OR 1.12 [95% confidence interval, CI, 1.06-1.19] and 1.28 [95% CI 1.20-1.36] respectively). Patients with low-income status were more likely than those with high-income status to stop all antihypertensive therapy (OR 1.65 [95% CI 1.43-1.89]), which reflects a general trend toward discontinuation of therapy among these patients even before implementation of reference-based pricing.\n Reference-based pricing in British Columbia achieved a sustained reduction in drug expenditures, and no changes in overall use of antihypertensive therapy were observed. Further research is needed on the overall health and economic effects of such policies.",
"Reference pricing is a medication cost-sharing policy that fully covers medications which are less expensive than a standard reference price and requires patients to pay the extra cost of higher-priced drugs in a class of therapeutically substitutable drugs. Little information exists on the clinical and economic consequences. We analyzed changes in drug utilization, physician visits, hospitalizations, long-term care admissions, and expenditures after the introduction of reference pricing for dihydropyridine calcium channel blockers (CCBs) among patients aged 65 years or older in British Columbia, Canada.\n This quasiexperimental longitudinal study was performed in the setting of Pharmacare, the state-funded drug benefits plan of all elderly persons in British Columbia. Study patients comprised all elderly residents of British Columbia who were enrolled in the provincial health insurance program and received dihydropyridine CCBs at the time of the policy change (35,886) and a subgroup of high-priced dihydropyridine CCB users (23,116). We studied the implementation of reference drug pricing on Jan 1, 1997, affecting all elderly Pharmacare beneficiaries. The main outcome measures were drug utilization, drug expenditures, physician visits, hospitalizations, long-term care, and net savings.\n The start of reference pricing was followed by a significant reduction in high-priced dihydropyridine CCBs (-150 monthly doses per 10,000 elderly persons), with a corresponding increase in fully covered dihydropyridine CCBs (+116). Overall, antihypertensive use did not decline (P =.46). Low-income status was a risk factor for discontinuing treatment (odds ratio, 1.64; 95% confidence interval [CI], 1.36 to 1.99); however, this was already observed to a similar magnitude 12 months before reference pricing (odds ratio, 1.46). In the overall study cohort, there was no increase in rates of physician visits, hospitalizations, and long-term care admissions. However, the 9% of patients who actually switched medications showed an 18% increase (95% CI, 8% to 28%) in physician visits and an increase of Canadian $13 (95% CI, Canadian $3 to Canadian $24) in costs of physician visits per patient as compared with nonswitchers during the transition but not afterward. This temporary increase may have been a result of additional prescribing and monitoring in switchers. Changes in drug expenditures and physician services resulted in net savings of Canadian $1.6 million in the first 12 months of policy implementation.\n Reference pricing as implemented in British Columbia may be a model for successful pharmaceutical cost-containment without adversely affecting patients or cost-shifting.",
"Rising costs of medications and inequities in access have sparked calls for drug policy reform in the United States and Canada. Control of drug expenditures by prescription cost-sharing for elderly persons and poor persons is a contentious issue because little is known about the health impact in these subgroups.\n To determine (1) the impact of introducing prescription drug cost-sharing on use of essential and less essential drugs among elderly persons and welfare recipients and (2) rates of emergency department (ED) visits and serious adverse events associated with reductions in drug use before and after policy implementation.\n Interrupted time-series analysis of data from 32 months before and 17 months after introduction of a prescription coinsurance and deductible cost-sharing policy in Quebec in 1996. Separate 10-month prepolicy control and postpolicy cohort studies were conducted to estimate the impact of the drug reform on adverse events.\n A random sample of 93 950 elderly persons and 55 333 adult welfare medication recipients.\n Mean daily number of essential and less essential drugs used per month, ED visits, and serious adverse events (hospitalization, nursing home admission, and mortality) before and after policy introduction.\n After cost-sharing was introduced, use of essential drugs decreased by 9.12% (95% confidence interval [CI], 8.7%-9.6%) in elderly persons and by 14.42% (95% CI, 13.3%-15.6%) in welfare recipients; use of less essential drugs decreased by 15.14% (95% CI, 14.4%-15.9%) and 22.39% (95% CI, 20.9%-23.9%), respectively. The rate (per 10 000 person-months) of serious adverse events associated with reductions in use of essential drugs increased from 5.8 in the prepolicy control cohort to 12.6 in the postpolicy cohort in elderly persons (a net increase of 6.8 [95% CI, 5.6-8.0]) and from 14.7 to 27.6 in welfare recipients (a net increase of 12.9 [95% CI, 10.2-15.5]). Emergency department visit rates related to reductions in the use of essential drugs also increased by 14.2 (95% CI, 8.5-19.9) per 10 000 person-months in elderly persons (prepolicy control cohort, 32.9; postpolicy cohort, 47.1) and by 54.2 (95% CI, 33.5-74.8) among welfare recipients (prepolicy control cohort, 69.6; postpolicy cohort, 123.8). These increases were primarily due to an increase in the proportion of recipients who reduced their use of essential drugs. Reductions in the use of less essential drugs were not associated with an increase in risk of adverse events or ED visits.\n In our study, increased cost-sharing for prescription drugs in elderly persons and welfare recipients was followed by reductions in use of essential drugs and a higher rate of serious adverse events and ED visits associated with these reductions.",
"Two programs to reduce expenditures for common gastrointestinal drugs were introduced simultaneously by British Columbia (BC) Pharmacare in 1995. Reference-based pricing restricted reimbursement for all histamine-2 receptor antagonists (H2RAs) to the cost of the least expensive H2RA available, generic cimetidine. Special authority restricted reimbursement for proton pump inhibitors (PPIs) to patients who met certain eligibility criteria. We evaluated the effect of reference-based pricing for H2RAs and special authority for PPIs on dispensing and reimbursement for senior citizen beneficiaries of BC Pharmacare.\n Itemized monthly claims data for upper gastrointestinal drugs were obtained from BC Pharmacare for all beneficiaries 65 years of age or older. Periods before and after implementation of reference-based pricing and special authority were compared with respect to defined daily doses dispensed per 100,000 beneficiaries, BC Pharmacare reimbursement per 100,000 beneficiaries, BC Pharmacare reimbursement per defined daily dose and beneficiary contributions per defined daily dose. We used regression models to project forward trends in expenditures observed before implementation of the new policies and hence to estimate accrued cost savings.\n Before reference-based pricing and special authority, the numbers of defined daily doses that were dispensed and total BC Pharmacare reimbursements for H2RAs appeared to be declining gradually, whereas those for PPIs were rising. With reference-based pricing, the monthly defined daily dose of cimetidine dispensed increased more than 4-fold, to 116,257 per 100,000 beneficiaries, while those of other restricted H2RAs decreased by more than half, to 50,927 per 100,000 beneficiaries. Special authority immediately reduced the dispensed volumes of PPIs by one-fourth, but growth in volume then appeared to resume at its previous rate. The estimated annualized cost savings achieved by reference-based pricing and special authority were $1.8 million to $3.2 million for H2RAs (depending on the estimation method used) and $5.5 million for PPIs. However, beneficiary contributions for H2RAs increased from negligible amounts to approximately 16% of total drug expenditures.\n Reference-based pricing and special authority appear to have been successful in altering prescribing habits and reducing provincial expenditures for upper gastrointestinal drugs, but they have increased the financial burden on senior citizen beneficiaries.",
"To describe the effects of introducing the Minimum Pricing Policy (MPP) and generic (brand) substitution in 1990 and 1994 respectively on the dispensing of Pharmaceutical Benefits Scheme (PBS) prescriptions both at the aggregate and individual patient level.\n The relative proportion of prescriptions with a brand premium and those at benchmark was examined 4 years after introduction of the MPP and again 5 years later after generic substitution by pharmacists was permitted. To determine the impact of a price signal at the individual level, case studies involving a patient tracking methodology were conducted on two drugs (fluoxetine and ranitidine) that received a brand premium.\n From a zero base when the MPP was introduced in 1990, there were 5.4 million prescriptions (17%) dispensed for benchmark products 4 years later in 1994. At this stage generic (brand) substitution by pharmacists was then permitted and the market share of benchmark brands increased to 45% (25.2 million) by 1999. In the patient tracking studies, a significantly lower proportion of patients was still taking the premium brand of fluoxetine 3 months after the introduction of a price signal compared with patients taking paroxetine which did not have a generic competitor. This was also the case for the premium brand of ranitidine when compared to famotidine. The size of the price signal also had a marked effect on dispensing behaviour with the drug with the larger premium (fluoxetine) showing a significantly greater switch away from the premium brand to the benchmark product.\n The introduction in 1990 of the Minimum Pricing Policy without allowing generic substitution had a relatively small impact on the selection of medicines within the Pharmaceutical Benefits Scheme. However the effect of generic substitution at the pharmacist level, which was introduced in December 1994, resulted in a marked increase in the percentage of eligible PBS items dispensed at benchmark. Case studies showed a larger premium resulted in a greater shift of patients from drugs with a brand premium to the benchmark alternative.",
"To estimate the effect of reference pricing (RP) of nonsteroidal anti-inflammatory drugs (NSAIDs) on drug subsidy program and beneficiary expenditures on analgesic drugs.\n Monthly claims data from Pharmacare, the public drug subsidy program for seniors in British Columbia, Canada, over the period of February 1993 to June 2001.\n RP limits drug plan reimbursement of interchangeable medicines to a reference price, which is typically equal to the price of the lowest cost interchangeable drug; any cost above that is borne by the patient. Pharmacare introduced two different forms of RP to the NSAIDs, Type 1 in April 1994 and Type 2 in November 1995. Under Type 1 RP, generic and brand versions of the same NSAID are considered interchangeable, whereas under Type 2 RP different NSAIDs are considered interchangeable. We extrapolated average reimbursement per day of NSAID therapy over the months before RP to estimate what expenditures would have been without the policies. These counterfactual predictions were compared with actual values to estimate the impact of the policies; the estimated impacts on reimbursement rates were multiplied by the postpolicy volume of NSAIDS dispensed, which appeared unaffected by the policies, to estimate expenditure changes.\n After Type 2 RP, program expenditures declined by $22.7 million (CAN), or $4 million (CAN), annually cutting expenditure by about half. Most savings accrued from the substitution of low-cost NSAIDs for more costly alternatives. About 20 percent of savings represented expenditures by seniors who elected to pay for partially reimbursed drugs. Type 1 RP produced one-quarter the savings of type 2 RP.\n Type 2 RP of NSAIDs achieved its goal of reducing drug expenditures and was more effective than Type 1 RP. The effects of RP on patient health and associated health care costs remain to be investigated."
] |
We found relatively few studies of pricing policies. The majority of the studies dealt with reference pricing. They had few methodological limitations. Based on the evidence in this review, mostly from senior citizens in British Columbia, Canada, reference drug pricing can reduce third party drug expenditures by inducing a shift in drug use towards less expensive drugs. We found no evidence of adverse effects on health and no clear evidence of increased health care utilisation. The analysis and reporting of the effects on patient drug expenditures were limited in the included studies and administration costs were not reported.
|
CD005133
|
[
"22094954",
"12937241",
"16780548",
"7487465",
"11920308",
"8304654",
"18622294",
"11003347",
"9013456",
"11571454",
"20547904",
"17973956",
"10320384",
"2547256"
] |
[
"Valganciclovir prophylaxis versus preemptive therapy in cytomegalovirus-positive renal allograft recipients: 1-year results of a randomized clinical trial.",
"Pre-emptive therapy of CMVpp65 antigen positive renal transplant recipients with oral ganciclovir: a randomized, comparative study.",
"Prophylactic versus preemptive oral valganciclovir for the management of cytomegalovirus infection in adult renal transplant recipients.",
"Preemptive ganciclovir therapy in cytomegalovirus-seropositive renal transplants recipients.",
"Preemptive use of oral ganciclovir to prevent cytomegalovirus infection in liver transplant patients: a randomized, placebo-controlled trial.",
"High-dose acyclovir compared with short-course preemptive ganciclovir therapy to prevent cytomegalovirus disease in liver transplant recipients. A randomized trial.",
"Prophylaxis followed by preemptive therapy versus preemptive therapy for prevention of human cytomegalovirus disease in pediatric patients undergoing liver transplantation.",
"Cytomegalovirus antigenemia directed pre-emptive prophylaxis with oral versus I.V. ganciclovir for the prevention of cytomegalovirus disease in liver transplant recipients: a randomized, controlled trial.",
"Control of cytomegalovirus-associated morbidity in renal transplant patients using intensive monitoring and either preemptive or deferred therapy.",
"Prospective randomized trial to assess the value of preemptive oral therapy for CMV infection following liver transplantation.",
"Extended valganciclovir prophylaxis to prevent cytomegalovirus after lung transplantation: a randomized, controlled trial.",
"Valacyclovir prophylaxis versus preemptive valganciclovir therapy to prevent cytomegalovirus disease after renal transplantation.",
"Valacyclovir for the prevention of cytomegalovirus disease after renal transplantation. International Valacyclovir Cytomegalovirus Prophylaxis Transplantation Study Group.",
"Prevention of cytomegalovirus-related death by passive immunization. A double-blind placebo-controlled study in kidney transplant recipients treated for rejection."
] |
[
"Cytomegalovirus (CMV) prevention can be achieved by prophylaxis or preemptive therapy. We performed a prospective randomized trial to determine whether renal transplant recipients with a positive CMV serostatus (R+) had a higher rate of CMV infection and disease after transplantation when treated preemptively for CMV infection, compared with primary valganciclovir prophylaxis.\n Prophylaxis was 2 × 450 mg oral valganciclovir/day for 100 days; preemptive patients were monitored by CMV-polymerase chain reaction (PCR), and after a positive PCR test received 2 × 900 mg valganciclovir/day for at least 14 days followed by secondary prophylaxis. Valganciclovir dosage was adjusted according to renal function. Patients are followed up for 5 years and initial 12-month data are presented. Two hundred and ninety-six recipients were analyzed (168 donor/recipient seropositive [D+/R+], 128 donor seronegative/recipient seropositive [D-/R+]; 146 receiving prophylaxis and 150 preemptive therapy).\n Overall, CMV infection (asymptomatic CMV viral load ≥ 400 CMV DNA copies/mL proven by CMV-PCR) was significantly higher in recipients under preemptive therapy (38.7% vs. 11.0%, P<0.0001), with the highest incidence in D+/R+ preemptive patients (53.8% vs. 15.6%, P<0.0001). D+/R+ recipients with preemptive therapy also had the highest rate of CMV disease (CMV syndrome and tissue-invasive disease that was clinically diagnosed and biopsy proven) (19.2% vs. 4.4%, P=0.003). Renal function assessed by creatinine clearance was similar for both groups. Graft loss occurred in 7 vs. 4 patients on preemptive versus prophylactic therapy (P>0.05). Tolerability was similar for both treatment groups.\n Oral valganciclovir prophylaxis significantly reduces CMV infection and disease, particularly for D+/R+ patients. Hence, our study supports routine prophylaxis for all D+/R+ recipients.",
"About one-quarter of renal transplant patients will suffer from symptomatic cytomegalovirus (CMV) disease if no preventive therapeutic measures are taken. In this prospective, randomized single-centre study pre-emptive therapy with oral ganciclovir is compared with conventional deferred treatment.\n Renal transplant recipients (n= 455) over 18 years of age were screened weekly for CMV pp65 antigenaemia during the first 12 weeks post-transplantation. If CMV pp65 antigen in leukocytes appeared within 8 weeks post-transplantation patients were randomized and included in the study. Five patients developed CMV disease before positive CMV pp65, and 14 patients with a positive antigen test developed CMV disease before randomization could take place, all these representing a limitation of the applicability of the results in the overall renal transplant population. Altogether 179 patients were not randomized for various reasons. Eighty patients completed the study, 42 were randomized to receive pre-emptive oral ganciclovir therapy and 38 to conventional deferred treatment (control group).\n Time from transplantation to start of ganciclovir capsules was 36 (12-60) days and duration of oral ganciclovir therapy was 49 (27-70) days, median (range). No patient in the pre-emptive treatment group, but nine of 38 patients (23.7%) in the control group, developed CMV disease during the first 12 weeks post-transplantation (P= 0.0009). In the period from 3 months to 1 year post-transplantation, two patients in each group developed CMV disease. There were no significant differences in acute rejection or renal function between treatment groups during the first post-transplant year.\n Pre-emptive oral ganciclovir therapy in renal transplant recipients during the first 12 weeks post-transplantation effectively prevents CMV disease during this time period. The incidence of late CMV disease (3 months to 1 year after transplantation) was similar in the two groups, indicating that pre-emptive therapy does not result in late onset of CMV disease.",
"Prophylaxis reduces cytomegalovirus (CMV) disease, but is associated with increased costs and risks for side effects, viral resistance and late onset CMV disease. Preemptive therapy avoids drug costs but requires frequent monitoring and may not prevent complications of asymptomatic CMV replication. Kidney transplant recipients at risk for CMV (D+/R-, D+/R+, D-/R+) were randomized to prophylaxis (valganciclovir 900 mg q.d. for 100 days, n=49) or preemptive therapy (900 mg b.i.d. for 21 days, n=49) for CMV DNAemia (CMV DNA level>2000 copies/mL in >or=1 whole blood specimens by quantitative PCR) assessed weekly for 16 weeks and at 5, 6, 9 and 12 months. More patients in the preemptive group, 29 (59%) than in the prophylaxis group, 14 (29%) developed CMV DNAemia, p=0.004. Late onset of CMV DNAemia (>100 days after transplant) occurred in 11 (24%) randomized to prophylaxis, and none randomized to preemptive therapy. Symptomatic infection occurred in five patients, four (3 D+/R- and 1 D+/R+) in the prophylactic group and one (D+/R-) in the preemptive group. Peak CMV levels were highest in the D+/R- patients. Both strategies were effective in preventing symptomatic CMV. Overall costs were similar and insensitive to wide fluctuations in costs of either monitoring or drug.",
"To evaluate the efficacy, safety, and cost of preemptive ganciclovir therapy in cytomegalovirus (CMV)-seropositive renal transplant recipients treated with antilymphocyte antibody (ALA) preparations.\n A prospective, randomized trial at a 650-bed tertiary medical center hospital.\n Forty consecutive CMV-seropositive renal allograft recipients who underwent transplantation between January 1992 and January 1994 and were treated with ALA for induction immunosuppression or acute rejection therapy.\n The incidence and severity of CMV disease, length of hospitalization, and patient and allograft survival.\n Cytomegalovirus infection prophylaxis by use of intravenous ganciclovir during ALA therapy was administered to 22 patients (group 1) and the results were compared with those obtained in 18 control patients who did not receive prophylaxis for CMV disease (group 2).\n Preemptive ganciclovir therapy significantly reduced the incidence of CMV disease (P < .05) in CMV-seropositive renal transplant patients who were treated with ALA and was well tolerated. In addition, the cost of prophylactic therapy was offset by the decreased length of hospitalization observed in patients in group 1.\n Preemptive ganciclovir therapy provides a cost-effective approach toward significantly improving the outcome of renal transplantation in CMV-seropositive patients treated with ALA.",
"The use of postdetection antiviral treatment of cytomegalovirus (CMV) as a strategy to prevent infection and disease in solid-organ transplant patients has not been evaluated by placebo-controlled trials. We carried out such a study in 69 patients who had received liver transplants and had positive results of CMV polymerase chain reaction within 8 weeks after transplantation but did not have concomitant CMV infection or disease. These patients were randomly assigned to receive placebo or oral ganciclovir for 8 weeks. CMV infection developed in 21% and disease developed in 12% of placebo recipients (P =.022), compared with 3% and 0%, respectively, among ganciclovir recipients (P =.003). Similarly, in the placebo arm, 55% and 36% of CMV-negative patients who received organs from CMV-positive donors developed CMV infection or disease, respectively (P =.02), compared with 11% and 0% of such patients in the ganciclovir arm (P <.01). Oral ganciclovir administered on CMV detection by PCR prevents CMV infection or disease after liver transplantation.",
"To assess the efficacy of high-dose oral acyclovir therapy compared with preemptive, short-course ganciclovir therapy (administered only if cytomegalovirus [CMV] shedding occurred) to prevent CMV disease in liver transplant recipients.\n A randomized controlled trial.\n Liver transplant center at a university-affiliated Veterans Affairs Medical Center.\n 47 consecutive patients having liver transplantation.\n Patients were stratified by their CMV antibody status and the CMV antibody status of the donor and were randomly assigned to one of two treatment groups. Surveillance cultures for CMV (buffy coat and urine) were done every 2 to 4 weeks for 24 weeks in all patients. One group received high-dose oral acyclovir (800 mg four times daily). The experimental group received no acyclovir, but if surveillance cultures were positive, ganciclovir (5 mg/kg intravenously twice daily) was administered for 7 days.\n Cytomegalovirus shedding and CMV disease were measured in the two groups.\n Cytomegalovirus shedding before the onset of CMV disease occurred in 25% (6 of 24) of patients in the acyclovir group compared with 22% (5 of 23) in the experimental group. Cytomegalovirus disease developed in 29% (7 of 24) of the acyclovir group and in 4% (1 of 23) of the experimental group (P < 0.05). No hematologic toxicity occurred with ganciclovir.\n Oral acyclovir is ineffective prophylaxis against CMV in liver transplant recipients. Preemptive, short-course ganciclovir therapy in patients with CMV shedding was well tolerated and provided effective prophylaxis against subsequent CMV disease; this protocol targets the patients at risk for CMV disease and minimizes toxicity and expense.",
"Twenty-one pediatric liver transplant recipients were enrolled in a study comparing prophylaxis followed by preemptive therapy (10 patients) versus preemptive therapy alone (11 patients) for prevention of human cytomegalovirus (HCMV) disease. In the prophylaxis arm, patients were treated with ganciclovir for 30 days, then preemptive therapy was initiated with virologic monitoring for pp65 antigenemia. In the preemptive therapy arm, patients were treated on reaching 100,000 DNA copies/mL whole blood. An interim analysis showed that, although numbers of both infected and treated patients were comparable in the two arms, the median number of total days of antiviral therapy per patient (30 vs. 18, P<0.01) was significantly higher in the prophylaxis arm. No case of HCMV disease occurred in either arm. Therefore, the trial was interrupted and prophylaxis replaced with preemptive therapy alone. In parallel, the development of T-cell-mediated immune response was found to be comparable in both arms.",
"The efficacy of pre-emptively administered oral ganciclovir in preventing cytomegalovirus (CMV) disease has not been documented in liver transplant recipients. We sought to compare the efficacy of pre-emptive oral ganciclovir with that of i.v. ganciclovir for the prevention of CMV disease after liver transplantation, and to determine whether withholding prophylaxis in the absence of CMV antigenemia, reliably identified patients in whom no prophylaxis was necessary.\n Surveillance cultures for CMV pp65 antigenemia were performed in all patients at weeks 2, 4, 6, 8, 12, and 16. Patients with CMV antigenemia were randomized into two study groups. The experimental group received oral ganciclovir for 6 weeks (2 g t.i.d. for 2 weeks, then 1 g t.i.d. for 4 weeks), and the control group received i.v. ganciclovir (5 mg/kg q 12 hr) for 7 days.\n Of 72 consecutive liver transplant recipients studied, CMV antigenemia occurred in 31% (22 of 72). Twenty-two patients with asymptomatic antigenemia were randomized to two study groups. CMV disease (viral syndrome) occurred in 9% (1 of 11) of the patients in the i.v. ganciclovir group and in 0% (0 of 11) of the patients in the oral ganciclovir group. None of the study patients developed tissue invasive CMV disease. The median reduction in antigenemia level with oral ganciclovir was 55% at week 1, and 100% at week 2. Overall, 64% of the patients by week 1, 93% by week 2, and 100% by week 4 had antigenemia levels below the baseline after oral ganciclovir. Of 50 patients without CMV antigenemia, none developed CMV disease.\n Pre-emptive prophylaxis based on CMV antigenemia can effectively target the patients for CMV prophylaxis; 69% of the patients never received antiviral prophylaxis and did not develop CMV disease. Antiviral therapy instituted upon detection of antigenemia prevented tissue invasive CMV in both ganciclovir groups. Pre-emptively administered oral ganciclovir was effective as prophylaxis for CMV disease after liver transplantation.",
"The objective of this randomized, prospective study was to compare preemptive to deferred treatment of cytomegalovirus (CMV) infection in high-risk renal transplant recipients. Conducted at a university-affiliated transplant center, the study included 36 renal allograft recipients with donor or recipient CMV-seropositivity who received anti-thymocyte induction therapy. Ganciclovir was administered intravenously for 21 days upon detection of CMV viremia (preemptive, N = 15) or detection of CMV viremia associated with a CMV syndrome (deferred, N = 21). Shell vial culture, conventional culture, and polymerase chain reaction (PCR) were performed upon buffy-coat specimens weekly for 12 to 16 wk. CMV and non-CMV-associated charges were calculated. The comparative sensitivities of PCR, shell vial culture, and conventional culture were 91%, 44%, and 47%, respectively. A delay in specimen processing of > 24 h severely compromised the sensitivity of culture techniques but not that of PCR. Preemptive therapy tended to decrease symptomatic CMV episodes (0.4 versus 0.6 episodes per patient randomized; P = 0.22). One patient in each group had organ involvement, and no patient died. Allograft function and survival were similar. Ganciclovir use was increased in the preemptive group (1.2 versus 0.6 courses per patient randomized; P = 0.02). CMV-associated charges were $10,368 (preemptive) versus $5,752 (deferred); P = 0.13. PCR is superior to conventional monitoring to detect CMV viremia. Culture cannot be considered the \"gold standard\" for detection of CMV viremia, especially when transport of specimens over distances results in processing delays. Preemptive therapy may reduce symptomatic CMV infections in renal transplant recipients. It was associated with higher CMV-related charges but equivalent overall charges versus deferred treatment with intensive monitoring. Either strategy can achieve control of CMV infection after renal transplantation.",
"With the development of sensitive tests to detect cytomegalovirus (CMV) viremia, preemptive approaches become a reasonable alternative to general CMV prophylaxis. We performed a randomized trial comparing pp65-antigenemia guided preemptive therapy using oral ganciclovir with symptom-triggered intravenous ganciclovir treatment.\n Eighty-eight of 372 liver transplant recipients developed antigenemia early after orthotopic liver transplantation. Twenty-eight symptomatic patients with antigenemia were excluded from randomization and treated with intravenous ganciclovir. Sixty pp65-antigen-positive asymptomatic patients were randomized to receive either oral ganciclovir 3x1 g/day for 14 days (group 1) or no preemptive treatment (group 2). Patients that developed CMV disease were treated with intravenous ganciclovir 2x5 mg/kg body weight for 14 days. The high-risk (Donor+/Recipient-) patients were equally distributed in the two study groups.\n Three of 30 (10%) patients on oral ganciclovir developed mild to moderate CMV disease compared with 6/30 (20%) patients in the control group. In the Donor+/Recipient- patients, the incidence of CMV disease was 1/6 and 3/7. All disease episodes resolved after intravenous treatment. The 1- and 3-year patient and organ survival was the same in the study groups and in the patients with or without CMV infection. No deaths related to CMV occurred.\n The positive predictive value of pp65-antigenemia for the development of CMV disease was very low, and, in 28/88 patients (32%), antigenemia did not precede symptoms. Therefore, pp65-antigenemia is of limited value in deciding on the timing and need for ganciclovir therapy after liver transplantation.",
"Cytomegalovirus (CMV) is the most prevalent opportunistic infection after lung transplantation. Current strategies do not prevent CMV in most at-risk patients.\n To determine whether extending prophylaxis with oral valganciclovir from the standard 3 months to 12 months after lung transplantation is efficacious.\n Randomized, clinical trial. Patients were randomly assigned by a central automated system to treatment or placebo. Patients and investigators were blinded to treatment status. (ClinicalTrials.gov registration number: NCT00227370)\n Multicenter trial involving 11 U.S. lung transplant centers.\n 136 lung transplant recipients who completed 3 months of valganciclovir prophylaxis.\n 9 additional months of oral valganciclovir (n = 70) or placebo (n = 66).\n The primary end point was freedom from CMV disease (syndrome or tissue-invasive) on an intention-to-treat basis 300 days after randomization. Secondary end points were CMV disease severity, CMV infection, acute rejection, opportunistic infections, ganciclovir resistance, and safety.\n CMV disease occurred in 32% of the short-course group versus 4% of the extended-course group (P < 0.001). Significant reductions were observed with CMV infection (64% vs. 10%; P < 0.001) and disease severity (110 000 vs. 3200 copies/mL, P = 0.009) with extended treatment. Rates of acute rejection, opportunistic infections, adverse events, CMV UL97 ganciclovir-resistance mutations, and laboratory abnormalities were similar between groups. During the 6 months after study completion, a low incidence of CMV disease was observed in both groups.\n Longer-term effects of extended prophylaxis were not assessed.\n In adult lung transplant recipients who have received 3 months of valganciclovir, extending prophylaxis by an additional 9 months significantly reduces CMV infection, disease, and disease severity without increased ganciclovir resistance or toxicity. A beneficial effect with regard to prevention of CMV disease seems to extend at least through 18 months after transplantation.",
"Both preemptive therapy and universal prophylaxis are used to prevent cytomegalovirus (CMV) disease after transplantation. Randomized trials comparing both strategies are sparse. Renal transplant recipients at risk for CMV (D+/R-, D+/R+, D-/R+) were randomized to 3-month prophylaxis with valacyclovir (2 g q.i.d., n = 34) or preemptive therapy with valganciclovir (900 mg b.i.d. for a minimum of 14 days, n = 36) for significant CMV DNAemia (>/=2000 copies/mL by quantitative PCR in whole blood) assessed weekly for 16 weeks and at 5, 6, 9 and 12 months. The 12-month incidence of CMV DNAemia was higher in the preemptive group (92% vs. 59%, p < 0.001) while the incidence of CMV disease was not different (6% vs. 9%, p = 0.567). The onset of CMV DNAemia was delayed in the valacyclovir group (37 +/- 22 vs. 187 +/- 110 days, p < 0.001). Significantly higher rate of biopsy-proven acute rejection during 12 months was observed in the preemptive group (36% vs. 15%, p = 0.034). The average CMV-associated costs per patient were $5525 and $2629 in preemptive therapy and valacyclovir, respectively (p < 0.001). However, assuming the cost of $60 per PCR test, there was no difference in overall costs. In conclusion, preemptive valganciclovir therapy and valacyclovir prophylaxis are equally effective in the prevention of CMV disease after renal transplantation.",
"Cytomegalovirus (CMV) disease is a major complication of organ transplantation. We hypothesized that prophylactic treatment with valacyclovir would reduce the risk of CMV disease.\n A total of 208 CMV-negative recipients of a kidney from a seropositive donor and 408 CMV-positive recipients were randomly assigned to receive either 2 g of valacyclovir or placebo orally four times daily for 90 days after transplantation, with the dose adjusted according to renal function. The primary end point was laboratory-confirmed CMV disease in the first six months after transplantation.\n Treatment with valacyclovir reduced the incidence or delayed the onset of CMV disease in both the seronegative patients (P<0.001) and the seropositive patients (P=0.03). Among the seronegative patients, the incidence of CMV disease 90 days after transplantation was 45 percent among placebo recipients and 3 percent among valacyclovir recipients. Among the seropositive patients, the respective values were 6 percent and 0 percent. At six months, the incidence of CMV disease was 45 percent among seronegative recipients of placebo and 16 percent among seronegative recipients of valacyclovir; it was 6 percent among seropositive placebo recipients and 1 percent among seropositive valacyclovir recipients. At six months, the rate of biopsy-confirmed acute graft rejection in the seronegative group was 52 percent among placebo recipients and 26 percent among valacyclovir recipients (P=0.001). Treatment with valacyclovir also decreased the rates of CMV viremia and viruria, herpes simplex virus disease, and the use of inpatient medical resources. Hallucinations and confusion were more common with valacyclovir treatment, but these events were not severe or treatment-limiting. The rates of other adverse events were similar among the groups.\n Prophylactic treatment with valacyclovir is a safe and effective way to prevent CMV disease after renal transplantation.",
"In a double-blind placebo-controlled study, the value of prophylactic anti-CMV immunoglobulin administration was evaluated in 39 kidney transplant recipients treated for rejection with rabbit antithymocyte globulin. Passive immunization completely prevented CMV-related death, although it did not reduce the incidence of CMV isolation, viremia, or disease. The effect of passive immunization was exclusively observed in CMV-seronegative recipients of a CMV-seropositive kidney donor. It could be demonstrated even when instituted when antirejection therapy was started. Seropositive recipients did not benefit from immunoglobulin treatment. Moreover, CMV-seronegative recipients of a kidney from a seronegative donor were not at risk for CMV infection at all. Therefore passive immunization should be restricted to seronegative recipients of seropositive allograft donors treated for rejection."
] |
Few RCTs have evaluated the effects of pre-emptive therapy to prevent CMV disease. Pre-emptive therapy is effective compared with placebo or standard care. Despite the inclusion of five additional studies in this update, the efficacy of pre-emptive therapy compared with prophylaxis to prevent CMV disease remains unclear due to significant heterogeneity between studies. Additional head-to-head studies are required to determine the relative benefits and harms of pre-emptive therapy and prophylaxis to prevent CMV disease in solid organ transplant recipients.
|
CD002130
|
[
"18946065",
"12204495",
"19463379",
"15618034",
"10476589",
"18984759",
"19262211",
"17442201",
"16533938",
"1671346",
"15234398",
"14724302",
"18707985",
"18364139",
"11419426",
"12971850",
"17616297",
"16275189",
"19332467",
"11688002",
"18371477",
"16682384",
"1472662",
"15784786",
"11597289",
"9727542",
"9582043",
"14744971",
"16275869",
"11818641",
"11419424",
"15531766",
"12297170",
"20368925",
"10732888",
"3792347",
"14993134",
"16760210",
"11265951",
"11145489",
"9599103",
"19023152",
"7514506",
"17383335",
"18756983"
] |
[
"Cardiovascular outcomes after a change in prescription policy for clopidogrel.",
"Effect of additional temporary glycoprotein IIb/IIIa receptor inhibition on troponin release in elective percutaneous coronary interventions after pretreatment with aspirin and clopidogrel (TOPSTAR trial).",
"Glycoprotein IIb/IIIa inhibitors improve outcome after coronary stenting in clopidogrel nonresponders: a prospective, randomized study.",
"Does pre-treatment with aspirin and loading dose clopidogrel obviate the need for glycoprotein IIb/IIIa antagonists during elective coronary stenting? A focus on peri-procedural myonecrosis.",
"Usefulness of platelet glycoprotein IIb/IIIa inhibitors in coronary stenting for reconstruction of complex lesions: procedural and 30 day outcome.",
"Aprotinin for patients exposed to clopidogrel before off-pump coronary bypass.",
"Glycoprotein IIB/IIIA inhibitor to reduce postpercutaneous coronary intervention myonecrosis and improve coronary flow in diabetics: the 'OPTIMIZE-IT' pilot randomized study.",
"Midterm outcomes of prospective, randomized, single-center study of the Janus tacrolimus-eluting stent for treatment of native coronary artery lesions.",
"Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR-REACT 2 randomized trial.",
"Immediate versus deferred beta-blockade following thrombolytic therapy in patients with acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI) II-B Study.",
"The additive value of tirofiban administered with the high-dose bolus in the prevention of ischemic complications during high-risk coronary angioplasty: the ADVANCE Trial.",
"A clinical trial of abciximab in elective percutaneous coronary intervention after pretreatment with clopidogrel.",
"Prehospital initiation of tirofiban in patients with ST-elevation myocardial infarction undergoing primary angioplasty (On-TIME 2): a multicentre, double-blind, randomised controlled trial.",
"Effect of tirofiban plus clopidogrel and aspirin on primary percutaneous coronary intervention via transradial approach in patients with acute myocardial infarction.",
"Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction.",
"[Early intravenous thrombolysis with recombinant tissue plasminogen activator for acute cerebral infarction].",
"Two-year clinical follow-up after sirolimus-eluting versus bare-metal stent implantation assisted by systematic glycoprotein IIb/IIIa Inhibitor Infusion in patients with myocardial infarction: results from the STRATEGY study.",
"Improvement in microvascular reflow and reduction of infarct size with adenosine in patients undergoing primary coronary stenting.",
"Abciximab in patients with acute ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention after clopidogrel loading: a randomized double-blind trial.",
"The effects of aprotinin and steroids on generation of cytokines during coronary artery surgery.",
"The efficacy and safety of short- and long-term dual antiplatelet therapy in patients with mild or moderate chronic kidney disease: results from the Clopidogrel for the Reduction of Events During Observation (CREDO) trial.",
"A comparison of dual vs. triple antiplatelet therapy in patients with non-ST-segment elevation acute coronary syndrome: results of the ELISA-2 trial.",
"Repeated dose administration of desmopressin acetate in uncomplicated cardiac surgery: a prospective, blinded, randomized study.",
"Effects of treating exhaustion in angioplasty patients on new coronary events: results of the randomized Exhaustion Intervention Trial (EXIT).",
"Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial.",
"Randomized, placebo-controlled trial of platelet glycoprotein IIb/IIIa blockade with primary angioplasty for acute myocardial infarction. ReoPro and Primary PTCA Organization and Randomized Trial (RAPPORT) Investigators.",
"Effect of local medical opinion leaders on quality of care for acute myocardial infarction: a randomized controlled trial.",
"Inhibition of restenosis with a paclitaxel-eluting, polymer-free coronary stent: the European evaLUation of pacliTaxel Eluting Stent (ELUTES) trial.",
"Preservation from left ventricular remodeling by front-integrated revascularization and stem cell liberation in evolving acute myocardial infarction by use of granulocyte-colony-stimulating factor (FIRSTLINE-AMI).",
"Prophylactic abciximab in elective coronary stenting: results of a randomized trial.",
"Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban.",
"Randomized clinical trial of abciximab in diabetic patients undergoing elective percutaneous coronary interventions after treatment with a high loading dose of clopidogrel.",
"Aprotinin reduces blood loss in off-pump coronary artery bypass (OPCAB) surgery.",
"Randomized controlled trial of clopidogrel to prevent primary arteriovenous fistula failure in hemodialysis patients.",
"Effect of glycoprotein IIb/IIIa receptor blockade with abciximab on clinical and angiographic restenosis rate after the placement of coronary stents following acute myocardial infarction.",
"Effect of early treatment with nifedipine in suspected acute myocardial infarction.",
"Three-year outcome after coronary stenting versus bypass surgery for the treatment of multivessel disease.",
"Amiodarone prophylaxis for atrial fibrillation of high-risk patients after coronary bypass grafting: a prospective, double-blinded, placebo-controlled, randomized study.",
"Oral amiodarone for prevention of atrial fibrillation after open heart surgery, the Atrial Fibrillation Suppression Trial (AFIST): a randomised placebo-controlled trial.",
"Novel dosing regimen of eptifibatide in planned coronary stent implantation (ESPRIT): a randomised, placebo-controlled trial.",
"Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction. Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) Study Investigators.",
"Efficacy of abciximab for patients undergoing balloon angioplasty: data from Japanese evaluation of c7E3 Fab for elective and primary PCI organization in randomized trial (JEPPORT).",
"Hydromorphone patient-controlled analgesia (PCA) after coronary artery bypass surgery.",
"Practical regimen for amiodarone use in preventing postoperative atrial fibrillation.",
"[A clinical trial of using antiplatelet therapy to prevent restenosis following peripheral artery angioplasty and stenting]."
] |
[
"Drug-reimbursement policies may have an adverse effect on patient outcomes if they interfere with timely access to efficacious medications for acute medical conditions. Clopidogrel in combination with aspirin is the recommended standard of care for patients receiving coronary stents to prevent thrombosis. We examined the population-level effect of a change by a Canadian provincial government in a pharmacy-benefits program from a prior-authorization policy to a less restrictive, limited-use policy on access to clopidogrel among patients undergoing percutaneous coronary intervention (PCI) with stenting after acute myocardial infarction.\n We conducted a population-based, retrospective, time-series analysis from April 1, 2000, to March 31, 2005, of all patients 65 years of age or older with acute myocardial infarction who underwent PCI with stenting in Ontario, Canada. The primary outcome was the composite rate of death, recurrent acute myocardial infarction, PCI, and coronary-artery bypass grafting at 1 year, with adjustment for sex and age. The secondary outcome was major bleeding.\n The rate of clopidogrel use within 30 days after hospital discharge following myocardial infarction increased from 35% in the prior-authorization period to 88% in the limited-use period. The median time to the first dispensing of a clopidogrel prescription decreased from 9 days in the first period to 0 days in the second period. The 1-year composite cardiovascular outcome significantly decreased from 15% in the prior-authorization group to 11% in the limited-use group (P=0.02). Rates of bleeding in the two groups did not change.\n The removal of a prior-authorization program led to improvement in timely access to clopidogrel for coronary stenting and improved cardiovascular outcomes.\n 2008 Massachusetts Medical Society",
"The Troponin in Planned PTCA/Stent Implantation With or Without Administration of the Glycoprotein IIb/IIIa Receptor Antagonist Tirofiban (TOPSTAR) trial investigated: 1) the amount of troponin T (TnT) release after nonacute, elective percutaneous coronary intervention (PCI) in patients pretreated with aspirin and clopidogrel; and 2) the effect of additional glycoprotein (GP) IIb/IIIa receptor inhibiton on postinterventional TnT release.\n No data are available yet as to whether additional administration of a GP IIb/IIIa receptor antagonist might be beneficial in patients undergoing elective PCI already pretreated with aspirin and clopidogrel.\n After bolus application of the study medication (tirofiban [T] or placebo [P]), PCI was performed followed by an 18-h continuous infusion of T/P. Primary end point of the study was incidence and amount of TnT release after elective PCI after 24 h.\n A total of 12 h after PCI troponin release was detected in 63% of the patients receiving P and in 40% of the patients receiving T (p < 0.05), after 24 h in 69% (P) and 48% (T) (p < 0.05) and after 48 h in 74% (P) versus 58% (T) (p < 0.08) of the patients. No differences were observed regarding major bleeding, intracranial bleeding or nonhemorrhagic strokes. After nine months a reduction of combined death/myocardial infarction/target vessel revascularization could be observed in the tirofiban group ([T] 2.3% vs. [P] 13.04%, p < 0.05).\n Troponin T release occurs after successful intervention in 74% of the patients undergoing elective PCI after 48 h even after pretreatment with aspirin and clopidogrel. The GP IIb/IIIa receptor antagonist tirofiban is able to decrease the incidence of troponin release significantly in this patient population.",
"The aim of this study was to assess, in clopidogrel nonresponders undergoing elective percutaneous coronary intervention (PCI), the benefit of adjusted antiplatelet therapy with glycoprotein (GP) IIb/IIIa antagonist administration during PCI for 1-month clinical outcome.\n Numerous biological studies have reported interindividual variability in platelet response to clopidogrel with clinical relevance, and high post-treatment platelet reactivity (adenosine diphosphate-induced aggregation >70%) has been proposed to define nonresponse to clopidogrel. These nonresponders might benefit from tailored antiplatelet therapy.\n One hundred forty-nine clopidogrel nonresponders referred for elective PCI were prospectively included and randomized to \"conventional group\" (n = 75) or \"active group\" with GP IIb/IIIa antagonist (n = 74). All patients received 250-mg aspirin and 600-mg clopidogrel before PCI and platelet testing.\n The rate of cardiovascular events at 1 month was significantly lower in the \"active group\" than in the \"conventional group\": 19% (n = 14) versus 40% (n = 30), p = 0.006, odds ratio: 2.8; 95% confidence interval: 1.4 to 6.0. No patient in either group had post-procedural Thrombolysis In Myocardial Infarction major bleeding or required transfusions.\n The present study suggested benefit of tailored antiplatelet therapy during elective PCI with GP IIb/IIIa antagonist for clopidogrel nonresponders without increased bleeding risk.",
"Although full platelet inhibition with aspirin and thienopyridines before coronary stenting has significantly reduced the risk of acute stent thrombosis, peri-procedural myonecrosis still occurs frequently and is associated with increased death rate. Whether further inhibition of platelet aggregation by a glycoprotein IIb/IIIa antagonist may provide an additional cardioprotection is unknown.\n A total of 200 patients pre-treated with aspirin and a loading dose of clopidogrel (450 mg) were randomized just before coronary intervention (percutaneous coronary intervention, PCI) to treatment with or without abciximab. Platelet aggregation was assessed in samples collected during the procedure and the degree of platelet aggregation inhibition was correlated with cardiac enzyme release post-PCI. Abciximab treatment achieved a more complete inhibition of aggregation than dual oral antiplatelet therapy alone (median value of 1 vs. 50%, normal 100%). Any pathological increase in creatinine kinase-MB (CK-MB) post-PCI was present in 21% of the abciximab group and in 22% of the no-abciximab group (P = 0.9). Also the occurrence of clinically relevant myonecrosis [myocardial infarction (MI) = CK-MB > 3x upper limit of normal] was not significantly influenced by treatment assignment: 9 vs. 10% (P = 0.9). In a multiple logistic regression model including clinical, angiographic, and procedural characteristics, post-PCI myonecrosis was not correlated with the degree of platelet aggregation inhibition but with procedural features (such as long inflation time) and with the presence of multi-vessel disease. There were no cases of acute or subacute stent thrombosis. At 6 months, major adverse cardiac events, including cardiac death, non-fatal MI, or target lesion revascularization occurred in 13% of abciximab patients and in 16% of the control patients (P = 0.6).\n In the studied patients scheduled for elective coronary stenting and pre-treated with aspirin and a loading dose of clopidogrel, further inhibition of platelet aggregation by abciximab does not afford additional cardioprotection. Our data suggest that distal athero-embolization rather than thrombo-embolization is involved in the phenomenon of myonecrosis post-elective stenting.",
"Intracoronary stent implantation during percutaneous transluminal coronary angioplasty (PTCA) has shown favorable results, reducing acute complications associated with PTCA, such as coronary artery dissection and abrupt or threatened vessel closure. However, treatment of lesions with a complex morphology and diffuse disease, requiring long or multiple coronary stents, is still associated with a poorer outcome. We investigated the hypothesis that abciximab might lead to a different outcome in patients with complex coronary lesions, which require long or multiple stent implantation.\n One hundred and six patients were randomized to receive either a combination of abciximab (bolus and 12 hour infusion) and weight-adjusted low-dose heparin or weight-adjusted heparin alone and followed up to 30 days.\n The procedural success rate was 100% in both groups of patients. In the control group a composite rate of major adverse events such as any death irrespective of cause, Q wave or non-Q wave myocardial infarction, acute or subacute stent thrombosis and urgent revascularization of 15.3% was shown at 30-day follow-up. The use of abciximab reduced the composite adverse event rate to 3.7% (76% absolute reduction, p < 0.05).\n The use of abciximab during high risk stenting is safe and reduces the risk of cardiac events at 30-day follow-up as compared to standard treatment with heparin. A longer follow-up period is warranted to confirm the beneficial effects observed at 30 days with abciximab in this setting.",
"To verify whether low-dose aprotinin reduces blood loss and blood product usage in patients with clopidogrel exposure within 5 days before off-pump coronary artery bypass, 51 patients with clopidogrel exposure were randomized in a double-blind fashion to receive low-dose aprotinin (25 patients), or placebo (26 patients). The baseline characteristics and number of distal anastomoses in the patients in each group were comparable. Time between the last dose of clopidogrel and start of the operation was similar in both groups, as was mean left ventricular ejection fraction. Chest tube drainage, blood product usage, and reoperation rate were significantly higher in the placebo group. In patients with unstable angina and recent clopidogrel exposure who are undergoing off-pump coronary artery bypass, intraoperative administration of low-dose aprotinin is recommended to reduce blood loss and transfusion requirements.",
"Subgroup analyses of trials enrolling acute coronary syndrome patients suggest that inhibition of glycoprotein IIb/IIIa can improve the outcome of diabetic patients undergoing percutaneous coronary interventions (PCIs), possibly by improving microvascular perfusion. However, the efficacy of small-molecule IIb/IIIa receptor inhibitors to improve microvascular perfusion in stable diabetic patients undergoing elective PCI has not been specifically investigated.\n We randomized consecutive stable diabetic patients, undergoing elective PCI, to tirofiban or placebo groups along with double antiplatelet therapy. High-dose bolus (25 microg/kg per 3 min) of tirofiban was administered immediately before PCI followed by 8 h continuous infusion (0.15 microg/kg per min). Postprocedural myonecrosis was assessed prospectively by measurement of cardiac troponin T (cTnT) at 6 and 24 h after PCI. The primary end-points were post-PCI coronary flow estimated by corrected thrombolysis in myocardial infarction frame count and post-PCI myocardial infarction. Platelet aggregation was measured by platelet function analyser-100 values.\n Forty-six patients entered the study (22 randomized to placebo and 24 randomized to tirofiban). The study drug was associated with a significant increase of platelet function analyser-100 values that peaked immediately after PCI and was maintained at 6 h (pre-PCI: 131 +/- 65 s; post-PCI: 222 +/- 49 s; after 6 h: 219 +/- 55 s).Post-PCI corrected thrombolysis in myocardial infarction frame count was similar in tirofiban and in placebo groups (10.2 +/- 3.6 vs. 12.0 +/- 7.6, P = 0.30, respectively). The prevalence of raised cTnT levels was similar in the two groups (25 vs. 30%, P = 0.56, respectively). At multivariate analysis, direct stenting (associated with reduced myonecrosis) and postdilatation (associated with increased myonecrosis) predicted cTnT elevation.\n A high-dose bolus of tirofiban in stable diabetic patients undergoing elective PCI, along with double antiplatelet therapy, was associated with a significant further inhibition of platelet aggregation which, however, did not translate in a lower incidence of post-PCI distal embolization.",
"Long-term efficacy and safety of tacrolimus-eluting stent (Janus) for treatment of coronary artery disease in percutaneous coronary interventions (PCI) \"real world\" is uncertain. The aim of this study was to evaluate the efficacy and safety of Janus stent for treating coronary heart disease in PCI daily practice, the safety of 4-month clopidogrel therapy after Janus stent implantation and the feasibility for treating patients with acute myocardial infarction (AMI) for first time.\n From February 20, 2006 to August 26, 2006, a total of 200 patients were enrolled and randomly assigned to receive either Janus stent (n = 100) or bare metal stent (Tecnic Carbostent, n = 100). All patients were administered with clopidogrel for 4 months and aspirin for life long after stenting.\n Baseline clinical and angiographic characteristics were comparable between the two groups. AMI was present in 37% of patients with Janus and 36% with Tecnic Carbostent. At an average of 246-day follow-up, major adverse cardiac events (MACE) was 6% with the Janus stent and 15% with the Tecnic Carbostent (P = 0.038). Primary events included 1 cardiac death, 1 myocardial infarction (MI) due to subacute stent thrombosis and 13 target lesion revascularizations (TLR) due to restenosis in patients with Tecnic Carbostent and 6 TLR due to restenosis in patients with Janus stent. Although all patients had discontinued clopidogrel for an average of 126 days, there was no additional thrombotic event in the two groups.\n Janus stent is efficient in reducing MACE compared with Tecnic Carbostent at an average of 8-month follow-up. Discontinuation of clopidogrel at 4 months after PCI is safe for patients with Janus stent, including AMI patients. Long-term efficacy of Janus stent in reducing restenosis requires further study.",
"No specifically designed studies have addressed the role of the glycoprotein IIb/IIIa inhibitor abciximab in patients with non-ST-segment elevation acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) after pretreatment with 600 mg of clopidogrel.\n To assess whether abciximab is associated with clinical benefit in high-risk patients with ACS undergoing PCI after pretreatment with 600 mg of clopidogrel.\n International, multicenter, randomized, double-blind, placebo-controlled study conducted from March 2003 through December 2005, enrolling 2022 patients (mean age, 66 years) with non-ST-segment elevation ACS undergoing PCI.\n Patients were assigned to receive either abciximab (0.25 mg/kg of body weight bolus, followed by a 0.125-microg/kg per minute [maximum, 10 microg/min] infusion for 12 hours, plus heparin, 70 U/kg of body weight) or placebo (placebo bolus and infusion of 12 hours, plus heparin bolus, 140 U/kg). All patients received clopidogrel, 600 mg, at least 2 hours prior to the procedure, as well as 500 mg of oral or intravenous aspirin.\n The primary end point was a composite of death, myocardial infarction, or urgent target vessel revascularization occurring within 30 days after randomization; secondary end points were rates of in-hospital major and minor bleeding.\n Of 2022 patients enrolled, 1012 were assigned to abciximab and 1010 to placebo. The primary end point was reached in 90 patients (8.9%) assigned to abciximab vs 120 patients (11.9%) assigned to placebo, a 25% reduction in risk with abciximab (relative risk [RR], 0.75; 95% CI, 0.58-0.97; P = .03). Among patients without an elevated troponin level, there was no difference in the incidence of primary end point events between the abciximab group (23/499 patients [4.6%]) and the placebo group (22/474 patients [4.6%]) (RR, 0.99; 95% CI, 0.56-1.76; P = .98), whereas among patients with an elevated troponin level, the incidence of events was significantly lower in the abciximab group (67/513 patients [13.1%]) compared with the placebo group (98/536 patients [18.3%]), which corresponds to an RR of 0.71 (95% CI, 0.54-0.95; P = .02) (P = .07 for interaction). There were no significant differences between the 2 groups regarding the risk of major and minor bleeding as well as need for transfusion.\n Abciximab reduces the risk of adverse events in patients with non-ST-segment elevation ACS undergoing PCI after pretreatment with 600 mg of clopidogrel. The benefits provided by abciximab appear to be confined to patients presenting with an elevated troponin level.\n ClinicalTrials.gov Identifier: NCT00133003.",
"In the Thrombolysis in Myocardial Infarction (TIMI) Phase II trial, patients received intravenous recombinant tissue-type plasminogen activator (rt-PA) and were randomized to either a conservative or an invasive strategy. Within this study, the effects of immediate versus deferred beta-blocker therapy were also assessed in patients eligible for beta-blocker therapy, a group of 1,434 patients of which 720 were randomized to the immediate intravenous group and 714 to the deferred group. In the immediate intravenous group, within 2 hours of initiating rt-PA metoprolol was given (5 mg intravenously at 2-minute intervals over 6 minutes, for a total intravenous dose of 15 mg, followed by 50 mg orally every 12 hours in the first 24 hours and 100 mg orally every 12 hours thereafter). The patients assigned to the deferred group received metoprolol, 50 mg orally twice on day 6, followed by 100 mg orally twice a day thereafter. The therapy was tolerated well in both groups and the primary end point, resting global ejection fraction at hospital discharge, averaged 50.5% and was virtually identical in the two groups. The regional ventricular function was also similar in the two groups. Overall, there was no difference in mortality between the immediate intravenous and deferred groups, but in the subgroup defined as low risk there were no deaths at 6 weeks among those receiving immediate beta-blocker therapy in contrast to seven deaths among those in whom beta-blocker therapy was deferred. These findings for a secondary end point in a subgroup were not considered sufficient to warrant a recommendation regarding clinical use. There was a lower incidence of reinfarction (2.7% versus 5.1%, p = 0.02) and recurrent chest pain (18.8% versus 24.1%, p less than 0.02) at 6 days in the immediate intravenous group. Thus, in appropriate postinfarction patients, beta-blockers are safe when given early after thrombolytic therapy and are associated with decreased myocardial ischemia and reinfarction in the first week but offer no benefit over late administration in improving ventricular function or reducing mortality.",
"We sought to determine the safety and efficacy of high-dose bolus (HDB) tirofiban in high-risk patients undergoing percutaneous coronary intervention (PCI).\n The use of HDB tirofiban in the catheterization laboratory is controversial. In particular, in patients with acute coronary syndromes undergoing PCI, there is no evidence that tirofiban administered in the catheterization laboratory is superior to heparin alone. This finding probably reflects the suboptimal platelet inhibition when tirofiban is employed at RESTORE (Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis) regimen.\n A total of 202 patients (mean age 69 +/- 8 years; 137 males [68%]) undergoing high-risk PCI, pretreated with thienopyridines, were consecutively randomized to HDB tirofiban (25 microg/kg/3 min, and infusion of 0.15 microg/kg/min for 24 to 48 h) or placebo immediately before the procedure and then followed for a median time of 185 days (range 45 to 324 days) for the occurrence of the primary composite end point of death, myocardial infarction, target vessel revascularization (TVR), and bailout use of glycoprotein (GP) IIb/IIIa inhibitors.\n The cumulative incidence of the primary end point was 35% and 20% in placebo and HDB tirofiban groups, respectively (hazard ratio 0.51, 95% confidence interval 0.29 to 0.88; p = 0.01). This difference was mainly due to the reduction of myocardial infarction and bailout use of GP IIb/IIIa inhibitors, with no significant effect on TVR or death. The safety profile did not differ between tirofiban and placebo.\n The use of tirofiban, when administered at HDB, is safe and significantly reduces the incidence of ischemic/thrombotic complications during high-risk PCI.",
"Whether the glycoprotein IIb/IIIa inhibitor abciximab is beneficial in patients undergoing elective percutaneous coronary intervention after pretreatment with clopidogrel is unknown.\n We enrolled 2159 patients with coronary artery disease who underwent a percutaneous coronary intervention: 1079 patients were randomly assigned in a double-blind manner to receive abciximab and 1080 patients to receive placebo. All patients were pretreated with a 600-mg dose of clopidogrel at least two hours before the procedure. The primary end point of the trial was the composite of death, myocardial infarction, and urgent target-vessel revascularization within 30 days after randomization.\n The incidence of the primary end point was 4 percent (45 patients) in the abciximab group, as compared with 4 percent (43 patients) in the placebo group (relative risk, 1.05; 95 percent confidence interval, 0.69 to 1.59; P=0.82). Most adverse events were myocardial infarctions: the incidence was 4 percent (40 patients) in the abciximab group and 4 percent (41 patients) in the placebo group (P=0.91). Twelve patients (1 percent) in the abciximab group and eight patients (1 percent) in the placebo group had major bleeding complications (P=0.37). Profound thrombocytopenia occurred in 10 patients (1 percent) in the abciximab group but in none in the placebo group (P=0.002).\n Our data suggest that in patients at low-to-intermediate risk who undergo elective percutaneous coronary intervention after pretreatment with a high loading dose of clopidogrel, abciximab is associated with no clinically measurable benefit within the first 30 days.\n Copyright 2004 Massachusetts Medical Society",
"The most effective magnitude and timing of antiplatelet therapy is important in patients with acute ST-elevation myocardial infarction (STEMI). We investigated whether the results of primary coronary angioplasty (PCI) can be improved by the early administration of the glycoprotein IIb/IIIa blocker tirofiban at first medical contact in the ambulance or referral centre.\n We undertook a double-blind, randomised, placebo-controlled trial in 24 centres in the Netherlands, Germany, and Belgium. Between June 29, 2006, and Nov 13, 2007, 984 patients with STEMI who were candidates to undergo PCI were randomly assigned to either high-bolus dose tirofiban (n=491) or placebo (N=493) in addition to aspirin (500 mg), heparin (5000 IU), and clopidogrel (600 mg). Randomisation was by blinded sealed kits with study drug, in blocks of four. The primary endpoint was the extent of residual ST-segment deviation 1 h after PCI. Analysis was by intention to treat. The trial is registered, number ISRCTN06195297.\n 936 (95%) patients were randomly assigned to treatment after a prehospital diagnosis of myocardial infarction in the ambulance. Median time from onset of symptoms to diagnosis was 76 min (IQR 35-150). Mean residual ST deviation before PCI (10.9 mm [SD 9.2] vs 12.1 mm [9.4], p=0.028) and 1 h after PCI (3.6 mm [4.6] vs 4.8 mm [6.3], p=0.003) was significantly lower in patients pretreated with high-bolus dose tirofiban than in those assigned to placebo. The rate of major bleeding did not differ significantly between the two groups (19 [4%] vs 14 [3%]; p=0.36).\n Our finding that routine prehospital initiation of high-bolus dose tirofiban improved ST-segment resolution and clinical outcome after PCI, emphasises that further platelet aggregation inhibition besides high-dose clopidogrel is mandated in patients with STEMI undergoing PCI.",
"Aspirin and clopidogrel can improve myocardial reperfusion and alleviate myocardial injury during percutaneous coronary intervention (PCI). Whether the addition of intravenous tirofiban during this procedure produces further benefit has not been clarified in ST segment elevation myocardial infarction (STEMI) patients. We evaluated this on STEMI patients who underwent primary PCI (p-PCI) via transradial artery approach.\n Consecutive patients were randomized into tirofiban group (n=72) or placebo group (n=78). Angiographic analysis included initial and final thrombolysis in myocardial infarction (TIMI) flow grade (TFG), corrected TIMI frame count (CTFC) and TIMI myocardial perfusion grade (TMPG) of the thrombotic vessel. Platelet aggregation rate (PAR), creatine phosphokinase (CPK), CPK isoenzyme MB (CPK-MB) and troponin I levels were measured and TIMI definitions were used to assess bleeding complications. Left ventricular performance parameters were investigated with equilibrium radionuclide ventriculography. Major adverse cardiac events (MACE) were followed up for 6 months.\n The cases of TFG 0 and 1 before PCI, TFG 0 when first crossing of guide wire were less, and the cases of TFG 3 after PCI was more in tirofiban group than those in placebo group. The final CTFC was fewer and the incidence of no reflow phenomenon was lower, as well the percentage of final TFG 3 was higher in tirofiban group than those in placebo group (all P<0.05). Mean peak CPK-MB was significantly lower, while the left ventricular performance parameters 1 week after PCI were much more improved in tirofiban group than those in the placebo group. PAR was significantly decreased shortly after tirofiban infusion. The incidence of 6-month MACE in tirofiban group was obviously lower than that in the placebo group. No statistical difference was noted between the two groups with regard to bleeding complications.\n Intravenous tirofiban infusion, in addition to aspirin and clopidogrel in STEMI patients with p-PCI via transradial artery access, can quickly inhibit platelet aggregation, loosen occlusive thrombus, improve myocardial reperfusion and reduce incidence of MACE with few complications of vessel access and bleeding.",
"When administered in conjunction with primary coronary stenting for the treatment of acute myocardial infarction, a platelet glycoprotein IIb/IIIa inhibitor may provide additional clinical benefit, but data on this combination therapy are limited.\n We randomly assigned 300 patients with acute myocardial infarction in a double-blind fashion either to abciximab plus stenting (149 patients) or placebo plus stenting (151 patients) before they underwent coronary angiography. Clinical outcomes were evaluated 30 days and 6 months after the procedure. The angiographic patency of the infarct-related vessel and the left ventricular ejection fraction were evaluated at 24 hours and 6 months.\n At 30 days, the primary end point--a composite of death, reinfarction, or urgent revascularization of the target vessel--had occurred in 6.0 percent of the patients in the abciximab group, as compared with 14.6 percent of those in the placebo group (P=0.01); at 6 months, the corresponding figures were 7.4 percent and 15.9 percent (P=0.02). The better clinical outcomes in the abciximab group were related to the greater frequency of grade 3 coronary flow (according to the classification of the Thrombolysis in Myocardial Infarction trial) in this group than in the placebo group before the procedure (16.8 percent vs. 5.4 percent, P=0.01), immediately afterward (95.1 percent vs. 86.7 percent, P=0.04), and six months afterward (94.3 percent vs. 82.8 percent, P=0.04). One major bleeding event occurred in the abciximab group (0.7 percent); none occurred in the placebo group.\n As compared with placebo, early administration of abciximab in patients with acute myocardial infarction improves coronary patency before stenting, the success rate of the stenting procedure, the rate of coronary patency at six months, left ventricular function, and clinical outcomes.",
"To evaluate the efficacy and safety of recombinant tissue plasminogen activator (rt-PA) and to explore the most suitable dosage of rt-PA in the early treatment of the Chinese patients with acute cerebral infarction (ACI).\n The patients who suited for the standard were divided into three groups. Group A received rt-PA at 0.9 mg/kg, group B received rt-PA at 0.7 mg/kg, and group C did not receive any thrombolytic therapy. In thrombolytic groups, rt-PA at 8 mg was injected intravenously in a bolus at first and then the rest was given over 60 minutes. The maximal dosage was 90 mg. The Chinese stroke scale (CSS) and Barthel Index (BI) were used to evaluate the recovery of neurological functions after rt-PA treatment for 24 hours and 90 days. The hemorrhagic rate and 30 days mortality rate were also analysed.\n In group A the CSS significant effective rate was 41.18 percent at 24 hours and 76.47 percent at 90 days after thrombolysis. At 90 days BI significant effective rate was 58.82 percent. At 30 days hemorrhagic rate was 8.82 percent and mortality rate was 5.88 percent. In group B, the CSS significant effective rate was 39.39 percent at 24 hours and 69.70 percent at 90 days. At 90 days, BI significant effective rate was 54.55 percent, and at 30 days, hemorrhagic rate was 9.09 percent and mortality rate was 9.09 percent. In group C, the CSS significant effective rate was 21.21 percent, at 24 hours and 30.30 percent at 90 days (P>0.05). At 90 days, BI was 21.21 percent the mortality rate was 9.09 percent. At 30 days the mortality rate was no significant difference within three groups At 90 days, significant effective rate was 73.13 percent vs. 30.30 percent in thrombolytic and control groups (P=0.001 7). The significant disability rate was 13.43 percent vs. 24.24 percent.\n For Chinese individuals, with ACI, rt-PA thrombolysis was effective and safe. The dosage of 0.9 mg/kg for foreign people also fitted for Chinese individuals.",
"We sought to investigate whether the previously reported midterm clinical benefit of planned sirolimus-eluting stent (SES) implantation in patients with ST-segment elevation myocardial infarction (STEMI) was maintained over a 24-month time period. Moreover, the distribution of clinical events in relation to thienopyridine discontinuation was thoroughly investigated.\n No randomized data are currently available on the safety/benefit profile of SES in this subset of patients beyond 12 months.\n Between March 2003 and April 2004, 175 patients with STEMI were randomly allocated to tirofiban infusion followed by SES or abciximab plus bare-metal stent (BMS). Complete follow-up information up to 720 days was available for all patients.\n The cumulative incidence of death, myocardial infarction (MI), or target vessel revascularization (TVR) remained lower in the tirofiban-SES compared with the abciximab-BMS group at 2 years (24.2% vs. 38.6%, respectively; hazard ratio [HR] 0.56 [95% confidence interval (CI) 0.33 to 0.98]; p = 0.038). The composite of death/MI was similar in the tirofiban-SES (16.1%) and the abciximab-BMS groups (20.5%, HR 0.77 [95% CI 0.38 to 1.55]; p = 0.43) while the need for TVR was markedly reduced (9.8% vs. 25.5%, respectively; HR 0.34 [95% CI 0.16 to 0.77]; p = 0.01) in the tirofiban-SES arm. The rate of confirmed, probable, or possible stent thrombosis did not differ in the 2 groups, nor the incidence of death/MI after thienopyridine discontinuation.\n The midterm clinical benefit of planned SES implantation assisted by tirofiban infusion in STEMI patients was mainly carried over after 2 years with no overall excess of late adverse events after thienopyridine discontinuation.",
"The aim of this study was to use myocardial contrast echocardiography to evaluate the effect of intravenous adenosine on microvascular reflow in patients with acute myocardial infarction who underwent primary coronary stenting (PCS). Thirty patients who underwent primary PCS for acute myocardial infarction were randomized to intravenous adenosine (50 to 70 mug/kg/min) or vehicle for 3 hours. Myocardial contrast echocardiography was performed before and sequentially after PCS to determine the risk area during coronary occlusion and infarct size. The risk area was similar in the adenosine- and placebo-treated patients. The infarct size as a ratio to the risk area was smaller in patients treated with adenosine when measured at 3 to 5 days (0.37 +/- 0.29 vs 0.68 +/- 0.25, p <0.01) and at 4 weeks (0.34 +/- 0.26 vs 0.60 +/- 0.21, p <0.01) after PCS. This effect was greatest when patency was achieved <4 hours after symptom onset (0.18 +/- 0.18 vs 0.74 +/- 0.31, p <0.05), with little effect after 4 hours. The relative microvascular blood volume in the risk area at 4 weeks was higher in patients receiving adenosine than in those receiving placebo (0.73 +/- 0.22 vs 0.57 +/- 0.20, p <0.01), and was highest when patency was achieved in <4 hours. In conclusion, the adjunctive use of intravenous adenosine after PCS reduces the infarct size relative to the risk area. This beneficial effect occurs primarily in those undergoing early intervention.",
"The glycoprotein IIb/IIIa receptor inhibitor abciximab has improved the efficacy of primary percutaneous coronary interventions in patients with acute myocardial infarction. However, it is not known whether abciximab remains beneficial after adequate clopidogrel loading in patients with acute ST-segment-elevation myocardial infarction.\n A total of 800 patients with acute ST-segment-elevation myocardial infarction within 24 hours from symptom onset, all treated with 600 mg clopidogrel, were randomly assigned in a double-blind fashion to receive either abciximab (n=401) or placebo (n=399) in the intensive care unit before being sent to the catheterization laboratory. The primary end point, infarct size measured by single-photon emission computed tomography with technetium-99m sestamibi before hospital discharge, was 15.7+/-17.2% (mean+/-SD) of the left ventricle in the abciximab group and 16.6+/-18.6% of the left ventricle in the placebo group (P=0.47). At 30 days, the composite of death, recurrent myocardial infarction, stroke, or urgent revascularization of the infarct-related artery was observed in 20 patients in the abciximab group (5.0%) and 15 patients in the placebo group (3.8%) (relative risk, 1.3; 95% CI, 0.7 to 2.6; P=0.40). Major bleeding complications were observed in 7 patients in each group (1.8%).\n Upstream administration of abciximab is not associated with a reduction in infarct size in patients presenting with acute myocardial infarction within 24 hours of symptom onset and receiving 600 mg clopidogrel.",
"To compare the efficacy of aprotinin and methylprednisolone in reducing cardiopulmonary bypass (CPB)-induced cytokine release, to evaluate the effect of myocardial cytokine release on systemic cytokine levels, and to determine the influence of cytokine release on perioperative and postoperative hemodynamics.\n Prospective, randomized clinical trial.\n University teaching hospital and clinics.\n Thirty patients undergoing elective coronary artery bypass graft surgery.\n Patients were randomly allocated into groups treated with aprotinin (n = 10) or methylprednisolone (n = 10) or into an untreated control group (n = 10). Aprotinin-treated patients received aprotinin as a high-dose regimen (6 x 10(6) KIU), and methylprednisolone-treated patients received methylprednisolone (30 mg/kg intravenously) before CPB.\n Patients were analyzed for hemodynamic changes and alveolar-arterial PO2 difference (AaDO2) until the first postoperative day. Plasma levels of proinflammatory cytokines (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta, IL-6, and IL-8) were measured in peripheral arterial blood immediately before the induction of anesthesia, 5 minutes before CPB, 3 minutes after the start of CPB, 2 minutes after the release of the aortic cross-clamp, 1 hour after CPB, 6 hours after CPB, and 24 hours after CPB; and in coronary sinus blood immediately before CPB and 2 minutes after the release of the aortic cross-clamp. The hemodynamic parameters did not differ among the groups throughout the study. After CPB, AaDO2 significantly increased (p < 0.05) in all groups. A significant decrease in AaDO2 was observed in aprotinin-treated patients at 24 hours after CPB compared with the other groups (p < 0.05). TNF-alpha level from peripheral arterial blood significantly increased in control patients 1 hour after CPB (p < 0.01) and did not significantly increase in methylprednisolone-treated patients throughout the study. In all groups, IL-6 levels increased after the release of the aortic cross-clamp and reached peak values 6 hours after CPB. At 6 hours after CPB, the increase in IL-6 levels in methylprednisolone-treated patients was significantly less compared with levels measured in control patients and aprotinin-treated patients (p < 0.001). In control patients, IL-8 levels significantly increased 2 minutes after the release of the aortic cross-clamp (p < 0.05), and peak values were observed 1 hour after CPB (p < 0.01). IL-8 levels in control patients were significantly higher compared with patients treated with aprotinin and patients treated with methylprednisolone 1 hour after CPB (p < 0.05).\n This study showed that methylprednisolone suppresses TNF-alpha, IL-6, and IL-8 release; however, aprotinin attenuates IL-8 release alone. Methylprednisolone does not produce any additional positive hemodynamic and pulmonary effects. An improved postoperative AaDO2 was observed with the use of aprotinin.\n Copyright 2001 by W.B. Saunders Company",
"Mild and moderate chronic kidney disease (CKD) is associated with decreased survival and increased adverse events after a percutaneous coronary intervention (PCI). Therapy with clopidogrel decreases adverse events in large patient populations. Therefore, we sought to determine the efficacy and safety of long-term clopidogrel therapy in patients with CKD.\n Two thousand two patients from the CREDO trial in whom an elective PCI of a single or multiple vessels was planned were analyzed. Patients were randomly assigned to a 300-mg loading dose of clopidogrel before PCI followed by clopidogrel 75 mg/d for a year versus a placebo loading dose at the time of the PCI procedure and clopidogrel 75 mg/d for 28 days and placebo for the remainder of a year. Patients were categorized by their estimated creatinine clearance (>90 [normal, n = 999], 60-89 [mild CKD, n = 672], <60 mL/min [moderate CKD, n = 331]).\n Diminished renal function was associated with worse outcomes. Patients with normal renal function who received 1 year of clopidogrel had a marked reduction in death, myocardial infarction, or stroke compared with those who received placebo (10.4% vs 4.4%, P < .001), whereas patients with mild and moderate CKD did not have a significant difference in outcomes with clopidogrel therapy versus placebo (mild: 12.8% vs 10.3%, P = .30; moderate: 13.1% vs 17.8%, P = .24). Clopidogrel use was associated with an increased relative risk of major or minor bleeding, but this increased risk was not different based on renal function (relative risk 1.2, 1.3, 1.1).\n Clopidogrel in mild or moderate CKD patients may not have the same beneficial effect as it does in patients with normal renal function, but was not associated with a greater relative risk of bleeding based on renal function. Further studies are needed to define the role of clopidogrel therapy in patients with CKD.",
"To compare dual vs. triple antiplatelet pre-treatment in patients with non-ST-elevation acute coronary syndrome (NSTE ACS) who were planned for early catheterization.\n A total of 328 consecutive patients with NSTE ACS were included and were randomized to pre-treatment with dual (n = 166, aspirin, clopidogrel 600 mg) or triple antiplatelet therapy (n = 162, aspirin, clopidogrel 300 mg, and Tirofiban). The primary endpoint was enzymatic infarct size, defined as cumulative LDH release (LDHQ(48)). Initial TIMI flow of the culprit vessel was a pre-specified secondary endpoint. Angiography was performed in 98% of patients at a median of 23 h after admission. Enzymatic infarct size (median, 25-75%) was 166 (60-349) IU/L in the triple group compared with 193 (75-466) IU/L in the dual group (P = 0.2). Initial TIMI 3 flow of the culprit vessel was significantly more often observed after triple antiplatelet therapy (67 vs. 47%, P = 0.002). At 30 days follow-up, myocardial infarction (MI) occurred in 46% of patients in the triple antiplatelet group, compared with 57% in the dual antiplatelet group, P = 0.052. No significant difference in bleeding was present.\n This study showed that in patients with NSTE ACS, triple antiplatelet pre-treatment was associated with a non-significant reduction in enzymatic infarct size, a significantly better initial perfusion of the culprit vessel, and a trend towards a better survival without death or MI. Further, large-scale studies should be performed to find whether the beneficial trend in favour of triple antiplatelet pre-treatment can be reproduced.",
"The effects of single or repeated doses of desmopressin on blood loss were examined in uncomplicated cardiac surgery, while assessing the potential for thrombogenic side effects. Seventy patients undergoing elective coronary artery bypass grafting (CABG) were studied. Patients were randomized into three blinded groups: Group I received DDAVP (0.3 micrograms/kg), IV, after cardiopulmonary bypass (CPB) and 12 hours later in the Intensive Care Unit (ICU); Group II, DDAVP (0.3 micrograms/kg), IV, after termination of CPB and saline (placebo) 12 hours later in the ICU; Group III, saline (placebo) IV after CPB and 12 hours later in the ICU. Blood loss and bleeding time decreased for Group I at 24 hours (P < 0.04) when compared to Group III; however, blood product replacement, as well as intraoperative and total blood loss at 36 hours, were not different among treatment and control groups. There were four myocardial infarctions recorded in Group I, two in Group II, and one in Group III. These differences were not found to be statistically significant. It is concluded that in routine CABG the prophylactic use of single or repeat dose DDAVP does not effectively decrease blood loss or blood product replacement.",
"Extreme fatigue is a common complaint in percutaneous coronary intervention (PCI) patients, and is associated with an increased risk for new cardiac events. The objective of the Exhaustion Intervention Trial (EXIT) was to determine whether a behavioral intervention on exhaustion reduces the risk of a new coronary event after PCI.\n Seven hundred ten consecutive patients, ages 35 to 68 years, who felt exhausted after PCI were randomized into an intervention group and a usual-care group. The intervention was based on group therapy focusing on stressors leading to exhaustion, and on support for recovery by promoting rest and making rest more efficient. One month after PCI, 50% of the patients felt exhausted. The intervention reduced the odds of remaining exhausted at 18 months by 56% in those without a previous history of coronary artery disease (CAD) (OR = 0.44; 95% CI 0.29-0.66), but had no effect on exhaustion in those with a history of CAD (OR = 0.93; 95% CI 0.56-1.55; p = .78). The intervention did not reduce the risk of a new coronary event within 2 years (RR = 1.14; 95%CI 0.82-1.57). Post-hoc analyses suggest that the effect of the intervention was limited by a positive history of CAD, the presence of a chronic, painful condition (especially rheumatism), and by opposite effects on early and late cardiac events.\n A behavioral intervention in PCI patients has a beneficial effect on feelings of exhaustion. It could not be demonstrated that the intervention reduces the risk of a new coronary event within 2 years.",
"Activation of the coagulation system and depletion of endogenous anticoagulants are frequently found in patients with severe sepsis and septic shock. Diffuse microthrombus formation may induce organ dysfunction and lead to excess mortality in septic shock. Antithrombin III may provide protection from multiorgan failure and improve survival in severely ill patients.\n To determine if high-dose antithrombin III (administered within 6 hours of onset) would provide a survival advantage in patients with severe sepsis and septic shock.\n Double-blind, placebo-controlled, multicenter phase 3 clinical trial in patients with severe sepsis (the KyberSept Trial) was conducted from March 1997 through January 2000.\n A total of 2314 adult patients were randomized into 2 equal groups of 1157 to receive either intravenous antithrombin III (30 000 IU in total over 4 days) or a placebo (1% human albumin).\n All-cause mortality 28 days after initiation of study medication.\n Overall mortality at 28 days in the antithrombin III treatment group was 38.9% vs 38.7% in the placebo group (P =.94). Secondary end points, including mortality at 56 and 90 days and survival time in the intensive care unit, did not differ between the antithrombin III and placebo groups. In the subgroup of patients who did not receive concomitant heparin during the 4-day treatment phase (n = 698), the 28-day mortality was nonsignificantly lower in the antithrombin III group (37.8%) than in the placebo group (43.6%) (P =.08). This trend became significant after 90 days (n = 686; 44.9% for antithrombin III group vs 52.5% for placebo group; P =.03). In patients receiving antithrombin III and concomitant heparin, a significantly increased bleeding incidence was observed (23.8% for antithrombin III group vs 13.5% for placebo group; P<.001).\n High-dose antithrombin III therapy had no effect on 28-day all-cause mortality in adult patients with severe sepsis and septic shock when administered within 6 hours after the onset. High-dose antithrombin III was associated with an increased risk of hemorrhage when administered with heparin. There was some evidence to suggest a treatment benefit of antithrombin III in the subgroup of patients not receiving concomitant heparin.",
"The benefit of catheter-based reperfusion for acute myocardial infarction (MI) is limited by a 5% to 15% incidence of in-hospital major ischemic events, usually caused by infarct artery reocclusion, and a 20% to 40% need for repeat percutaneous or surgical revascularization. Platelets play a key role in the process of early infarct artery reocclusion, but inhibition of aggregation via the glycoprotein IIb/IIIa receptor has not been prospectively evaluated in the setting of acute MI.\n Patients with acute MI of <12 hours' duration were randomized, on a double-blind basis, to placebo or abciximab if they were deemed candidates for primary PTCA. The primary efficacy end point was death, reinfarction, or any (urgent or elective) target vessel revascularization (TVR) at 6 months by intention-to-treat (ITT) analysis. Other key prespecified end points were early (7 and 30 days) death, reinfarction, or urgent TVR. The baseline clinical and angiographic variables of the 483 (242 placebo and 241 abciximab) patients were balanced. There was no difference in the incidence of the primary 6-month end point (ITT analysis) in the 2 groups (28.1% and 28.2%, P=0.97, of the placebo and abciximab patients, respectively). However, abciximab significantly reduced the incidence of death, reinfarction, or urgent TVR at all time points assessed (9.9% versus 3.3%, P=0.003, at 7 days; 11.2% versus 5.8%, P=0.03, at 30 days; and 17.8% versus 11.6%, P=0.05, at 6 months). Analysis by actual treatment with PTCA and study drug demonstrated a considerable effect of abciximab with respect to death or reinfarction: 4.7% versus 1.4%, P=0.047, at 7 days; 5.8% versus 3.2%, P=0.20, at 30 days; and 12.0% versus 6.9%, P=0.07, at 6 months. The need for unplanned, \"bail-out\" stenting was reduced by 42% in the abciximab group (20.4% versus 11.9%, P=0.008). Major bleeding occurred significantly more frequently in the abciximab group (16.6% versus 9.5%, P=0.02), mostly at the arterial access site. There was no intracranial hemorrhage in either group.\n Aggressive platelet inhibition with abciximab during primary PTCA for acute MI yielded a substantial reduction in the acute (30-day) phase for death, reinfarction, and urgent target vessel revascularization. However, the bleeding rates were excessive, and the 6-month primary end point, which included elective revascularization, was not favorably affected.",
"The effectiveness of recruiting local medical opinion leaders to improve quality of care is poorly understood.\n To evaluate a guideline-implementation intervention of clinician education by local opinion leaders and performance feedback to (1) increase use of lifesaving drugs (aspirin and thrombolytics in eligible elderly patients, beta-blockers in all eligible patients) for acute myocardial infarction (AMI), and (2) decrease use of a potentially harmful therapy (prophylactic lidocaine).\n Randomized controlled trial with hospital as the unit of randomization, intervention, and analysis.\n Thirty-seven community hospitals in Minnesota.\n All patients with AMI admitted to study hospitals over 10 months before (1992-1993, N=2409) or after (1995-1996, N=2938) the intervention.\n Using a validated survey, we identified opinion leaders at 20 experimental hospitals who influenced peers through small and large group discussions, informal consultations, and revisions of protocols and clinical pathways. They focused on (1) evidence (drug efficacy), (2) comparative performance, and (3) barriers to change. Control hospitals received mailed performance feedback.\n Hospital-specific changes before and after the intervention in the proportion of eligible patients receiving each study drug.\n Among experimental hospitals, the median change in the proportion of eligible elderly patients receiving aspirin was +0.13 (17% increase from 0.77 at baseline), compared with a change of -0.03 at control hospitals (P=.04). For beta-blockers, the respective changes were +0.31 (63% increase from 0.49 at baseline) vs +0.18 (30% increase from baseline) for controls (P=.02). Lidocaine use declined by about 50% in both groups. The intervention did not increase thrombolysis in the elderly (from 0.73 at baseline), but nearly two thirds of eligible nonrecipients were older than 85 years, had severe comorbidities, or presented after at least 6 hours.\n Working with opinion leaders and providing performance feedback can accelerate adoption of some beneficial AMI therapies (eg, aspirin, beta-blockers). Secular changes in knowledge and hospital protocols may extinguish outdated practices (eg, prophylactic lidocaine). However, it is more difficult to increase use of effective but riskier treatments (eg, thrombolysis) for frail elderly patients.",
"The use of a stent to deliver a drug may reduce in-stent restenosis. Paclitaxel interrupts the smooth muscle cell cycle by stabilizing microtubules, thereby arresting mitosis.\n On the basis of prior animal studies, the European evaLUation of the pacliTaxel Eluting Stent (ELUTES) pilot clinical trial (n=190) investigated the safety and efficacy of V-Flex Plus coronary stents (Cook Inc) coated with escalating doses of paclitaxel (0.2, 0.7, 1.4, and 2.7 microg/mm2 stent surface area) applied directly to the abluminal surface of the stent in de novo lesions compared with bare stent alone. The primary efficacy end point was angiographic percent diameter stenosis at 6 months. At angiographic follow-up, percent diameter stenosis was 33.9+/-26.7% in controls (n=34) and 14.2+/-16.6% in the 2.7-microg/mm2 group (n=31; P=0.006). Late loss decreased from 0.73+/-0.73 to 0.11+/-0.50 mm (P=0.002). Binary restenosis (> or =50% at follow-up) decreased from 20.6% to 3.2% (P=0.056), with no significant benefit from intermediate paclitaxel doses. Freedom from major adverse cardiac events in the highest (effective) dose group was 92%, 89%, and 86% at 1, 6, and 12 months, respectively (P=NS versus control). No late stent thromboses were seen in any treated group despite clopidogrel treatment for 3 months only.\n Paclitaxel applied directly to the abluminal surface of a bare metal coronary stent, at a dose density of 2.7 microg/mm2, reduced angiographic indicators of in-stent restenosis without short- or medium-term side effects.",
"Considering experimental evidence that stem cells enhance myocardial regeneration and granulocyte colony-stimulating factor (G-CSF) mediates mobilization of CD34+ mononuclear blood stem cells (MNCCD34+), we tested the impact of G-CSF integrated into primary percutaneous coronary intervention (PCI) management of acute myocardial infarction in man.\n Fifty consecutive patients with ST-segment elevation myocardial infarction were subjected to primary PCI stenting with abciximab and followed up for 6 months; 89+/-35 minutes after successful PCI, 25 patients were randomly assigned in this pilot study (PROBE design) to receive subcutaneous G-CSF at 10 microg/kg body weight for 6 days in addition to standard care, including aspirin, clopidogrel, an ACE inhibitor, beta-blocking agents, and statins. By use of CellQuest software on peripheral blood samples incubated with CD45 and CD34, mobilized MNCCD34+ were quantified on a daily basis. With homogeneous demographics and clinical and infarct-related characteristics, G-CSF stimulation led to mobilization of MNCCD34+ to between 3.17+/-2.93 MNCCD34+/microL at baseline and 64.55+/-37.11 MNCCD34+/microL on day 6 (P<0.001 versus control); there was no indication of leukocytoclastic effects, significant pain, impaired rheology, inflammatory reactions, or accelerated restenosis at 6 months. Within 35 days, G-CSF and MNCCD34+ liberation led to enhanced resting wall thickening in the infarct zone of between 0.29+/-0.22 and 0.99+/-0.32 mm versus 0.49+/-0.29 mm in control subjects (P<0.001); under inotropic challenge with dobutamine (10 microg.kg(-1).min(-1)), wall motion score index showed improvement from 1.66+/-0.23 to 1.41+/-0.21 (P<0.004 versus control) and to 1.35+/-0.24 after 4 months (P<0.001 versus control), respectively, coupled with sustained recovery of wall thickening to 1.24+/-0.31 mm (P<0.001 versus control) at 4 months. Accordingly, resting wall motion score index improved with G-CSF to 1.41+/-0.25 (P<0.001 versus control), left ventricular end-diastolic diameter to 55+/-5 mm (P<0.002 versus control), and ejection fraction to 54+/-8% (P<0.001 versus control) after 4 months. Morphological and functional improvement with G-CSF was corroborated by enhanced metabolic activity and 18F-deoxyglucose uptake in the infarct zone (P<0.001 versus control).\n G-CSF and mobilization of MNC(CD34+) after reperfusion of infarcted myocardium may offer a pragmatic strategy for preservation of myocardium and prevention of remodeling without evidence of aggravated restenosis.",
"The use of abciximab (c7E3 Fab; ReoPro , Eli Lilly & Company, Indianapolis, Indiana) during percutaneous coronary intervention (PCI) decreases the incidence of early (30-day) and late (6-month to 1 year) adverse cardiac ischemic events. In a high-risk population, abciximab also reduced the need for target lesion revascularization. PCI of lesions with complex morphology, particularly long lesions, is associated with more complicated outcomes. The use of multiple and/or long intracoronary stents to cover long coronary lesions may lower the incidence of acute or subacute occlusion, but is still limited by a high late restenosis rate. We characterized patients undergoing elective implantation of long or multiple overlapping coronary stents and determined the impact of abciximab administration on clinical and angiographic outcomes.\n In a prospective, single-center randomized trial, a total of 107 patients undergoing elective implantation of long or multiple overlapping coronary stents were randomly assigned to receive either standard-dose heparin (n = 53) or abciximab plus low-dose heparin (n = 54). The use of abciximab was not associated with an increased incidence of bleeding or vascular complications compared to standard heparin regimen (3.7% versus 3.8%, respectively; p = NS). A 68% reduction in composite in-hospital cardiac events (i.e., death, myocardial infarction, urgent revascularization) was observed in the abciximab group (3.7% versus 11.5%, p = 0.1). At 6-month follow-up, a 48% reduction of target lesion revascularization (11% versus 21%; p = 0.1) and a decrease in binary angiographic restenosis were observed for abciximab-treated patients (17% versus 34%; p < 0.05).\n The peri-procedural use of abciximab during implantation of long or multiple overlapping coronary stents is safe and effective, as it does not increase bleeding or vascular complications compared to standard heparin anticoagulation and reduces the incidence of in-hospital adverse cardiac events; moreover, abciximab improves 6-month clinical and angiographic outcomes in such a complex setting.",
"There is continued debate as to whether a routine, early invasive strategy is superior to a conservative strategy for the management of unstable angina and myocardial infarction without ST-segment elevation.\n We enrolled 2220 patients with unstable angina and myocardial infarction without ST-segment elevation who had electrocardiographic evidence of changes in the ST segment or T wave, elevated levels of cardiac markers, a history of coronary artery disease, or all three findings. All patients were treated with aspirin, heparin, and the glycoprotein IIb/IIIa inhibitor tirofiban. They were randomly assigned to an early invasive strategy, which included routine catheterization within 4 to 48 hours and revascularization as appropriate, or to a more conservative (selectively invasive) strategy, in which catheterization was performed only if the patient had objective evidence of recurrent ischemia or an abnormal stress test. The primary end point was a composite of death, nonfatal myocardial infarction, and rehospitalization for an acute coronary syndrome at six months.\n At six months, the rate of the primary end point was 15.9 percent with use of the early invasive strategy and 19.4 percent with use of the conservative strategy (odds ratio, 0.78; 95 percent confidence interval, 0.62 to 0.97; P=0.025). The rate of death or nonfatal myocardial infarction at six months was similarly reduced (7.3 percent vs. 9.5 percent; odds ratio, 0.74; 95 percent confidence interval, 0.54 to 1.00; P<0.05).\n In patients with unstable angina and myocardial infarction without ST-segment elevation who were treated with the glycoprotein IIb/IIIa inhibitor tirofiban, the use of an early invasive strategy significantly reduced the incidence of major cardiac events. These data support a policy involving broader use of the early inhibition of glycoprotein IIb/IIIa in combination with an early invasive strategy in such patients.",
"Diabetic patients are at increased risk of adverse outcomes after percutaneous coronary interventions. Although subset analyses suggest particular benefit from the administration of abciximab in diabetic patients, no dedicated large randomized trials have been performed in diabetic patients undergoing percutaneous coronary intervention, and certainly not after pretreatment with a high loading dose of clopidogrel.\n This study (Intracoronary Stenting and Antithrombotic Regimen: Is Abciximab a Superior Way to Eliminate Elevated Thrombotic Risk in Diabetics [ISAR-SWEET] Study) enrolled 701 diabetic patients with coronary artery disease who underwent an elective percutaneous coronary intervention after pretreatment with a 600-mg dose of clopidogrel >2 hours before the procedure: 351 patients were randomly assigned to abciximab and 350 patients to placebo. The primary end point of the trial was the composite incidence of death and myocardial infarction at 1 year. The frequency of angiographic restenosis (diameter stenosis > or =50%) was the secondary end point. The incidence of death or myocardial infarction was 8.3% in the abciximab group and 8.6% in the placebo group (P=0.91), with a relative risk of 0.97 (95% CI, 0.58 to 1.62). The incidence of angiographic restenosis was 28.9% in the abciximab group and 37.8% in the placebo group (P=0.01), with a relative risk of 0.76 (95% CI, 0.62 to 0.94). The incidence of target lesion revascularization was 23.2% in the abciximab group and 30.4% in the placebo group (P=0.03).\n The findings of this study do not support a significant impact of abciximab on the risk of death and myocardial infarction in diabetic patients undergoing percutaneous coronary interventions after pretreatment with a 600-mg loading dose of clopidogrel at least 2 hours before the procedure. The present findings suggest, however, that abciximab reduces the risk of restenosis in diabetic patients receiving coronary bare metal stents.",
"Effects of aprotinin in off-pump coronary artery bypass (OPCAB) surgery have not yet been described. This study analyses hemostasiologic changes and potential benefit in OPCAB patients treated with aprotinin.\n In a prospective, double-blind, randomized study 47 patients undergoing OPCAB surgery were investigated. Patients received either aprotinin (2 x 10(6) KIU loading dose and 0.5 x 10(6) KIU/h during surgery, n=22) or saline solution (control, n=25). Activated clotting time was adjusted to a target of 250 s intraoperatively. Blood samples were taken up to 18h postoperatively: complete hematologic and hemostasiologic parameters including fibrinopeptide A (FPA) and D-dimer in a subgroup of 31 patients were analyzed. Blood loss, blood transfusion and other clinical data were collected.\n Both groups showed comparable demographic and intraoperative variables. Forty-one (87%) patients of the whole study group received aspirin within 7 days prior to surgery. Number of grafts per patient were comparable (2.9+/-1.0 [mean+/-SD] in the aprotinin group and 2.8+/-1.2 in control, P=0.83). Blood loss during the first 18 h in intensive care unit was significantly reduced in patients treated with aprotinin (median [25th-75th percentiles]: 500 [395-755] ml vs. 930 [800-1170] ml, P<0.001). Postoperatively only two patients (10%) in the aprotinin group received packed red blood cells, whereas eight (35%) in the control group (P=0.07). Perioperatively FPA levels reflecting thrombin generation were elevated in both groups. The increase in D-dimer levels after surgery was significantly inhibited in the aprotinin group (P<0.001). Early clinical outcome was similar in both groups.\n Aprotinin significantly reduces blood loss in patients undergoing OPCAB surgery. Inhibition of enhanced fibrinolysis can be observed. FPA generation during and after OPCAB surgery seems not to be influenced by aprotinin.",
"The optimal vascular access for chronic maintenance hemodialysis is the arteriovenous fistula (AVF). Several studies suggest a role for antiplatelet agents in the prevention of primary AVF failure. A double-blind, randomized trial was conducted to assess the efficacy and safety of clopidogrel in hemodialysis patients. Ninety three patients were randomized to receive 75 mg/daily of clopidogrel or placebo. The treatment was initiated 7-10 days prior to scheduled access surgery and continued up to six weeks postoperatively, and then patients were monitored for six months. The primary outcome was AVF failure eight weeks after fistula creation. With a permuted block randomization schedule, 46 patients received clopidogrel and 47 patients received control placebo. The primary AVF failures at two months were 21.6% in placebo group and 5.2% in clopidogrel group (P = 0.03). The hazard ratio for the incidence of primary AVF failure was 0.72 (CI 95%, 0.41-1.01). Analysis of covariables indicated that this effect occurred principally as a result of clopidogrel administration. First hemodialysis from newly created AVF in clopidogrel group was significantly more successful than placebo group (P = 0.008). No life-threatening adverse event or severe bleeding was recorded in both groups. Clopidogrel seems to be effective and safe for prevention of primary AVF failure in hemodialysis patients.",
"In the Intracoronary Stenting and Antithrombotic Regimen-2 trial (ISAR-2), we sought to investigate the effect of abciximab on angiographic and clinical restenosis after stenting following acute myocardial infarction (AMI). We also intended to assess the impact of abciximab on clinical outcome in this setting.\n It is unclear whether abciximab reduces neointima formation after stenting. Such an effect may be particularly prominent in thrombus-containing lesions.\n Patients undergoing stenting within 48 h after onset of AMI were randomly assigned to receive either standard-dose heparin or abciximab plus reduced-dose heparin. Of 401 patients randomized, 366 without 30-day adverse events were eligible for six-month angiographic follow-up. Scheduled angiography was performed in 80% of these patients.\n By 30 days, the composite clinical end point of death, reinfarction, and target lesion revascularization (TLR) was reached in 5.0% of the abciximab group and in 10.5% of the control group (p = 0.038). At one year, absolute reduction in the composite clinical end point by abciximab was still 5.7% but had lost its statistical significance. Our primary end point, late lumen loss, was 1.26+/-0.85 mm with abciximab and 1.21+/-0.74 mm with standard heparin (p = 0.61), and binary angiographic restenosis rates were 31.1% and 30.6%, respectively (p = 0.92).\n In patients undergoing stenting following AMI, abciximab exerted beneficial effects by substantially reducing the 30-day rate of major adverse cardiac events. During one-year follow-up, there was no additional benefit from a reduction in TLR nor did abciximab reduce angiographic restenosis.",
"In this single centre prospective, double blind study, 98 patients with suspected acute myocardial infarction (AMI) were randomized, within six hours, to nifedipine 10 mg (46 patients) or placebo (52 patients) both administered sublingually. The delay time from onset of chest pain to treatment was 3.33 +/- 0.2 hours (mean +/- SEM) and 3.28 +/- 0.18 hours for the nifedipine and placebo treated groups, respectively. Treatment was continued orally for 3 days. AMI was confirmed in 28 patients given nifedipine and 23 patients given placebo. Infarct sizing by CK-MB isoenzyme release was possible, for technical reasons, in only 23 patients on nifedipine and 17 patients on placebo. CK-MB isoenzyme release was 710 +/- 104 IU l-1 and 655 +/- 118 IU l-1 for the nifedipine and placebo treated groups respectively (P greater than 0.05). In the acute coronary insufficiency (ACI) group--18 patients given nifedipine and 29 patients given placebo--there was no significant difference in duration of admission, urgent cardiac readmission or progression to AMI within one month. Study withdrawal occurred in 15.3%--8 nifedipine and 7 placebo. Overall, one month mortality was 10.2% with 5 deaths in both the nifedipine and placebo treated groups. Early treatment with nifedipine did not reduce enzymatically determined infarct size or one month mortality in patients with AMI, or reduce one month morbidity or mortality in patients with ACI.",
"The primary results of Arterial Revascularization Therapy Study reported a greater need for repeated revascularization after percutaneous coronary intervention with stenting (PCI). However, PCI was less expensive than coronary artery bypass grafting (CABG) and offered the same degree of protection against death, stroke, and myocardial infarction.\n Patients with multivessel disease (n=1205) were randomly assigned to either CABG or PCI and followed up for up to 3 years. Survival rates without stroke or myocardial infarction were similar in each group at 1 year and 3 years (90.5% versus 91.4% for PCI versus CABG at 1 year and 87.2% versus 88.4% for PCI versus CABG at 3 years). However, the respective repeat revascularization rates were 21.2% and 26.7% at 1 and 3 years in patients allocated to PCI, compared with 3.8% and 6.6% in patients allocated to CABG (P<0.0001). Diabetes (P<0.0009) and maximal pressure for stent deployment (P<0.002) are the strongest independent predictors of events at 3 years after PCI, whereas left anterior descending coronary artery grafting (P<0.006) is the best predictor of event-free survival at 3 years after CABG. The incremental cost of surgery compared with PCI for an event-free patient was 19 257 at 1 year but decreased to 10 492 at 3 years. It remained at 142 391 at 3 years when revascularization procedures were excluded in the efficacy end point, however.\n Three-year survival rates without stroke and myocardial infarction are identical in both groups, and the cost/benefit ratio of stenting is determined primarily by the increasing need for revascularization in the PCI group.",
"Atrial fibrillation (AF) occurs often in patients after coronary artery bypass grafting (CABG) and can result in increased morbidity and mortality. Previous studies using P-wave signal-averaged electrocardiogram (P-SAECG) have shown that patients with a longer filtered P-wave duration (FPD) have a high risk of AF after CABG. We have shown that patients with an FPD > or = 124 ms and a root-mean-square voltage of the last 20 ms of the P-wave 20 < or = 3.7 microV have an increased risk of AF after surgery. Accordingly, the aim of this study was to investigate whether or not prophylactic peri-operative administration of amiodarone could reduce the incidence of AF in this high-risk group undergoing CABG identified by P-SAECG.\n In this prospective, double-blinded, placebo-controlled, randomized study, 110 patients received either amiodarone (n = 55) or placebo (n = 55). During CABG, two patients of both groups died. Amiodarone was given as 600 mg oral single dose one day before and from days 2 through 7 after surgery. In addition, amiodarone was also administered intravenously during surgery in a 300-mg bolus for 1 h and as a total maintenance dose of 20 mg/kg weight over 24 h on the first day following surgery. The primary endpoint was the occurrence of AF after CABG. The secondary endpoint was the hospitalization length of stay after CABG. The baseline characteristics were similar in both treatment groups. The incidence of post-operative AF was significantly higher in the placebo group compared with the amiodarone group (85 vs. 34% of patients, P < 0.0001). The prophylactic therapy with amiodarone significantly reduced the intensive care (1.8 +/- 1.7 vs. 2.4 +/- 1.5 days, P = 0.001) and hospitalization length of stay (11.3 +/- 3.4 vs. 13.0 +/- 4.3 days, P = 0.03). In the amiodarone group, concentrations of amiodarone and desethylamiodarone differed significantly between patients with AF and sinus rhythm (amiodarone: 0.96 +/- 0.5 vs. 0.62 +/- 0.4 microg/mL, P = 0.02; desethylamiodarone: 0.65 +/- 0.2 vs. 0.48 +/- 0.1 microg/mL, P = 0.04).\n The incidence of post-operative AF among high-risk patients was significantly reduced by a prophylactic amiodarone treatment resulting in a shorter time of intensive care unit and hospital stay. Our data supports the prophylactic use of amiodarone in peri-operative period in patients at high risk for AF after CABG.",
"Beta-blockers and amiodarone reduce the frequency of atrial fibrillation after open-heart surgery but the effectiveness of oral amiodarone in older patients already receiving beta-blockers is unknown. We have assessed the efficacy of oral amiodarone in preventing atrial fibrillation in patients aged 60 years or older undergoing open-heart surgery.\n We did a randomised, double-blind placebo-controlled trial in which patients undergoing open-heart surgery (n=220, average age 73 years) received amiodarone (n=120) or placebo (n=100). Patients enrolled less than 5 days before surgery received 6 g of amiodarone or placebo over 6 days beginning on preoperative day 1. Patients enrolled at least 5 days before surgery received 7 g over 10 days beginning on preoperative day 5.\n Patients on amiodarone had a lower frequency of any atrial fibrillation (22.5% vs 38.0%; p=0.01; absolute difference 15.5% [95% CI 3.4-27.6%]), and there were significant differences in favour of the active drug for symptomatic atrial fibrillation (4.2% vs 18.0%, p=0.001), cerebrovascular accident (1.7% vs 7.0%, p=0.04), and postoperative ventricular tachycardia (1.7% vs 7.0%, p=0.04). Beta-blocker use (87.5% amiodarone vs 91.0% placebo), nausea (26.7% vs 16.0%), 30-day mortality (3.3% vs 4.0%), symptomatic bradycardia (7.5% vs 7.0%), and hypotension (14.2% vs 10.0%) were similar.\n Oral amiodarone prophylaxis in combination with beta-blockers prevents atrial fibrillation and symptomatic fibrillation and reduces the risk of cerebrovascular accidents and ventricular tachycardia.",
"The platelet glycoprotein IIb/IIIa inhibitors, although effective in reducing ischaemic complications of percutaneous coronary intervention, are used in few coronary stent implantation procedures. ESPRIT (Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy) is a randomised, placebo-controlled trial to assess whether a novel, double-bolus dose of eptifibatide could improve outcomes of patients undergoing coronary stenting.\n We recruited 2064 patients undergoing stent implantation in a native coronary artery. Immediately before percutaneous coronary intervention, patients were randomly allocated to receive eptifibatide, given as two 180 microg/kg boluses 10 min apart and a continuous infusion of 2.0 microg/kg/min for 18-24 h, or placebo, in addition to aspirin, heparin, and a thienopyridine. The primary endpoint was the composite of death, myocardial infarction, urgent target vessel revascularisation, and thrombotic bailout glycoprotein IIb/IIIa inhibitor therapy within 48 h after randomisation. The key secondary endpoint was the composite of death, myocardial infarction, or urgent target vessel revascularisation at 30 days.\n The trial was terminated early for efficacy. The primary endpoint was reduced from 10.5% (108 of 1024 patients on placebo [95% CI 8.7-12.4%]) to 6.6% (69 of 1040 [5.1-8.1%]) with treatment (p=0.0015). The key 30 day secondary endpoint was also reduced, from 10.5% (107 of 1024 patients on placebo [8.6-12.3%]) to 6.8% (71 of 1040 [5.3-8.4%]; p=0.0034). There was consistency in reduction of events across all components of the composite endpoint and among the major subgroups. Major bleeding was infrequent but arose more often with eptifibatide than placebo (1.3%, 13 of 1040 [0.7-2.1%]) vs 0.4%, 4 of 1024 [0.1-1.0%]; p=0.027).\n Routine glycoprotein IIb/IIIa inhibitor pretreatment with eptifibatide substantially reduces ischaemic complications in coronary stent intervention and is better than a strategy of reserving treatment to the bailout situation.",
"Antithrombotic therapy improves the prognosis of patients with acute coronary syndromes, yet the syndromes remain a therapeutic challenge. We evaluated tirofiban, a specific inhibitor of the platelet glycoprotein IIb/IIIa receptor, in the treatment of unstable angina and non-Q-wave myocardial infarction.\n A total of 1915 patients were randomly assigned in a double-blind manner to receive tirofiban, heparin, or tirofiban plus heparin. Patients received aspirin if its use was not contraindicated. The study drugs were infused for a mean (+/-SD) of 71.3+/-20 hours, during which time coronary angiography and angioplasty were performed when indicated after 48 hours. The composite primary end point consisted of death, myocardial infarction, or refractory ischemia within seven days after randomization.\n The study was stopped prematurely for the group receiving tirofiban alone because of excess mortality at seven days (4.6 percent, as compared with 1.1 percent for the patients treated with heparin alone. The frequency of the composite primary end point at seven days was lower among the patients who received tirofiban plus heparin than among those who received heparin alone (12.9 percent vs. 17.9 percent; risk ratio, 0.68; 95 percent confidence interval, 0.53 to 0.88; P=0.004). The rates of the composite end point in the tirofiban-plus-heparin group were also lower than those in the heparin-only group at 30 days (18.5 percent vs. 22.3 percent, P=0.03) and at 6 months (27.7 percent vs. 32.1 percent, P=0.02). At seven days, the frequency of death or myocardial infarction was 4.9 percent in the tirofiban-plus-heparin group, as compared with 8.3 percent in the heparin-only group (P=0.006). The comparable figures at 30 days were 8.7 percent and 11.9 percent (P=0.03), respectively, and those at 6 months were 12.3 percent and 15.3 percent (P=0.06). The benefit was consistent in the various subgroups of patients and in those treated medically as well as those treated with angioplasty. Major bleeding occurred in 3.0 percent of the patients receiving heparin alone and 4.0 percent of the patients receiving combination therapy (P=0.34).\n When administered with heparin and aspirin, the platelet glycoprotein IIb/IIIa receptor inhibitor tirofiban was associated with a lower incidence of ischemic events in patients with acute coronary syndromes than in patients who received only heparin and aspirin.",
"The efficacy and safety of abciximab were investigated in Japanese patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction (MI) or unstable angina.\n The 973 patients were randomized into 3 groups: the low-dose group (L group) received bolus injection of 0.20 mg/kg followed by 12-h infusion; the high-dose group (H group) received bolus injection of 0.25 mg/kg followed by 12-h infusion; the placebo group (P group) received bolus and infusion of placebo. The incidence of the primary endpoint (30-day post-PCI coronary events: death, MI or urgent revascularization) was 3.6%, 1.6%, and 4.1% in the P, L, and H groups, respectively, with no significant difference between the P and L groups (P=0.104) or between the P and H groups (P=0.772). The incidence of bleeding tended to increase in a dose-dependent manner.\n No significant difference in the incidence of coronary events was found between the placebo and abciximab groups, so the efficacy of abciximab in preventing post-PCI coronary events in Japanese patients was not confirmed.",
"We conducted a study to compare the effectiveness of patient-controlled analgesia (PCA) technique to conventional analgesic therapy (CAT) after coronary artery bypass graft (CABG). The PCA group received hydromorphone 0.1 mg.hr-1 basal infusion and bolus doses of 0.2 mg Q 5 min (maximum 1.2 mg.hr-1) while the CAT group received morphine 2.5 mg iv Q 30 min prn until extubation followed by prn meperidine 1 mg.kg-1 im Q 4 hr or acetaminophen 325 mg with codeine 30 mg po (1 or 2 tablets) when oral intake was possible. The degree of pain was assessed using a Visual Analogue Scale (VAS) starting after extubation and every 6-8 hr for the next 60 hr. Holter monitoring was initiated one hour after patient arrival in the Intensive Care Unit (ICU) and continued for 72 hr. Other measured variables were pulmonary function, sedation, side effects and total opioid requirements. Results show that the day-to-day VAS pain score decreased in the PCA group (P < 0.001) while it remained unchanged in CAT patients. The PCA patients had lower VAS pain scores at extubation (P < 0.05). During the third postoperative day, the PCA group had a lower VAS pain score, a lower incidence of severe pain defined as a score > 5 on the VAS scale, and a reduced incidence of myocardial ischaemia (P < 0.01). However, there was no difference in the duration, severity, area under the curve (AUC), or heart rate during ischaemic events. Postoperative pulmonary function was abnormal in both groups (NS) with minimal recovery by the fourth day.(ABSTRACT TRUNCATED AT 250 WORDS)",
"Postoperative atrial fibrillation occurs in 5% to 65% of patients undergoing cardiac surgery. Although postoperative atrial fibrillation is often regarded as a temporary, benign, operation-related problem, it is associated with a twofold to threefold increase in risk of adverse events, including permanent or transient stroke, acute myocardial infarction, and death.\n This randomized, controlled, double-blinded trial included 250 eligible consecutively enrolled patients undergoing coronary artery bypass grafting (CABG). They received 300 mg of amiodarone/placebo administered intravenously over 20 minutes on the first postoperative day and an oral dose of 600 mg of amiodarone or placebo twice daily for the first 5 postoperative days.\n The patients in amiodarone prophylaxis experienced a reduction in risk of atrial fibrillation of 14% (95% confidence interval [CI], 5.0% to 24%), with the number needed to treat at 6.9 (95% CI, 4.2 to 20), and the results for symptomatic atrial fibrillation showed a risk reduction of 18% (95% CI, 9.4% to 26), with the number needed to treat at 5.7 (95% CI, 3.9 to 11). Of the patients who developed atrial fibrillation in the placebo group, 84% experienced a symptomatic attack versus only 43% in the amiodarone group.\n Postoperative prophylaxis with a high dose of oral amiodarone after an intravenous bolus infusion is a safe, practical, feasible, and effective regimen for CABG patients. It significantly diminishes the occurrence of postoperative atrial fibrillation.",
"To evaluate the clinical effect and restenosis rate of antiplatelet therapy following peripheral artery angioplasty and stenting.\n After successful placement of peripheral artery stents to 103 patients with peripheral arterial occlusive disease (PAOD) in were randomized assigned to 2 groups: antiplatelet therapy group receiving clopidogrel 75 mg plus aspirin 100 mg (n = 56) and control group (n = 47) receiving anticoagulation therapy low molecular weight heparin (LWMH) for 7 d plus long-term warfarin. The patients were followed up 1 day, and 1, 6, 12, and 18 months after the operation to undergo color Doppler ultrasonography, and examinations of blood routine, bleeding time, coagulation time, and ankle-brachial Index. The primary endpoint events included major bleeding rate, and composite rate of restenosis and reocclusion. The secondary endpoint events included cardiovascular events, death, and adverse drug reaction.\n There were no significant differences in the baseline data between these two groups. The thrombotic occlusion rate was 1.8% in the antiplatelet group and 0% in control group, and the restenosis rate was 14.3% in the antiplatelet group and 25.5% in control group (both P > 0.05). The bleeding complication rate of the antiplatelet group was 1.8%, significantly lower than that of the anticoagulation group (19.1%, P < 0.01). There were not significant differences in cardiovascular event rate and mortality 18 months after operation between these two groups.\n Antiplatelet therapy combined with clopidogrel plus aspirin is effective and safe in preventing restenosis following peripheral artery angioplasty and stenting."
] |
When administered during PCI, intravenous IIb/IIIa blockers reduce the risk of death and of death or MI at 30 days and at six months, at a price of an increase in the risk of severe bleeding. The efficacy effects are homogeneous but are less marked in patients pre-treated with clopidogrel where they seem to be effective only in patients with ACS. When administered as initial medical treatment in patients with NSTEACS, these agents do not reduce mortality although they slightly reduce the risk of death or MI.
|
CD006114
|
[
"8803649",
"8889909",
"6407502",
"2110560",
"1299793",
"2507630",
"1810358",
"10695642",
"6407504",
"12858325",
"8690826",
"8923094",
"12616734",
"12590404",
"16160624",
"1904620",
"15706464",
"1909083",
"7588171",
"9164424",
"10736983",
"2115680",
"1546121",
"2491940",
"2120201",
"15243735",
"6819596",
"2127561",
"6407503",
"11354236",
"2143637",
"12393308",
"14604447",
"12823077",
"2663975",
"22298536",
"14632962",
"12237788",
"7884018",
"7814822"
] |
[
"Fluvoxamine versus imipramine and placebo: a double-blind comparison in depressed patients.",
"A comparison of fluvoxamine and fluoxetine in the treatment of major depression.",
"A double-blind comparative study of the clinical efficacy of fluvoxamine and chlorimipramine.",
"A double-blind, placebo-controlled trial of fluvoxamine versus imipramine in outpatients with major depression.",
"Perspectives in clinical psychopharmacology of amitriptyline and fluvoxamine. A double-blind study in depressed inpatients.",
"A placebo-controlled inpatient comparison of fluvoxamine maleate and imipramine in major depression.",
"A double-blind, randomised comparison of fluvoxamine with dothiepin in the treatment of depression in elderly patients.",
"Venlafaxine versus fluvoxamine in the treatment of delusional depression: a pilot double-blind controlled study.",
"A double-blind placebo-controlled study of fluvoxamine and imipramine in out-patients with primary depression.",
"Fluvoxamine versus fluoxetine in major depressive episode: a double-blind randomised comparison.",
"Fluvoxamine maleate in the treatment of depression: a single-center, double-blind, placebo-controlled comparison with imipramine in outpatients.",
"Efficacy and tolerability of citalopram in comparison with fluvoxamine in depressed outpatients: a double-blind, multicentre study. The LUCIFER Group.",
"[Comparative efficacy and tolerance of fluvoxamine and amitriptyline in the treatment of moderate and severe depression in mental hospital].",
"Fluvoxamine as effective as clomipramine against symptoms of severe depression: results from a multicentre, double-blind study.",
"Sertraline versus fluvoxamine in the treatment of elderly patients with major depression: a double-blind, randomized trial.",
"[Multicenter study comparing efficacy and tolerance of moclobemide and fluvoxamine in hospitalized and ambulatory patients with severe depressive episodes].",
"A comparative study of the efficacy and safety profiles between fluvoxamine and nortriptyline in Japanese patients with major depression.",
"Double-blind comparative multicentre study of fluvoxamine and mianserin in the treatment of major depressive episode in elderly people.",
"Fluvoxamine and clomipramine in depressed hospitalised patients: results from a randomised, double-blind study.",
"A double-blind comparison of fluvoxamine and paroxetine in the treatment of depressed outpatients.",
"[Fluoxetine versus fluvoxamine for treatment of chronic pain].",
"Response to total sleep deprivation before and during treatment with fluvoxamine or maprotiline in patients with major depression--results of a double-blind study.",
"Efficacy and tolerability of moclobemide compared with fluvoxamine in depressive disorder (DSM III). A French/Swiss double-blind trial.",
"Efficacy of fluvoxamine in obsessive-compulsive disorder. A double-blind comparison with placebo.",
"The role of neuropharmacologic selectivity in antidepressant action: fluvoxamine versus desipramine.",
"A double-blind randomized study comparing imipramine with fluvoxamine in depressed inpatients.",
"Fluvoxamine maleate, a serotonergic antidepressant; a comparison with chlorimipramine.",
"A double-blind, randomized comparison of fluvoxamine with mianserin in depressive illness.",
"Clinical trials of fluvoxamine vs chlorimipramine with single and three times daily dosing.",
"Antidepressant efficacy and tolerability of milnacipran, a dual serotonin and noradrenaline reuptake inhibitor: a comparison with fluvoxamine.",
"A controlled trial of fluvoxamine in obsessive-compulsive disorder: implications for a serotonergic theory.",
"CPT performance in major depressive disorder before and after treatment with imipramine or fluvoxamine.",
"Fluvoxamine CR in the long-term treatment of social anxiety disorder: the 12- to 24-week extension phase of a multicentre, randomized, placebo-controlled trial.",
"A double-blind, placebo-controlled study of the efficacy and safety of controlled-release fluvoxamine in patients with obsessive-compulsive disorder.",
"A double-blind comparison of fluoxetine, imipramine and placebo in outpatients with major depression.",
"A double-blind controlled comparison of fluoxetine and lofepramine in major depressive illness.",
"Double-blind comparison of fluoxetine and nortriptyline in the treatment of moderate to severe major depression.",
"Plasma levels of catecholamine metabolites predict the response to sulpiride or fluvoxamine in major depression.",
"Is baseline agitation a relative contraindication for a selective serotonin reuptake inhibitor: a comparative trial of fluoxetine versus imipramine.",
"A double-blind comparison of venlafaxine and fluoxetine in patients hospitalized for major depression and melancholia. The Venlafaxine French Inpatient Study Group."
] |
[
"Approximately 20 million patients suffer from major depressive disorder each year, indicating a need for antidepressant agents that are synonymous with effectiveness, tolerability and patient compliance. The authors examined the effects of fluvoxamine, a selective serotonin reuptake inhibitor, in the treatment of outpatients meeting DSM-III-R criteria for major depressive disorder. A randomized, double-blind, parallel group, placebo- and imipramine-controlled single center study was conducted in 150 outpatients. Patients were randomized to receive up to 150 mg/day of fluvoxamine as a single bedtime dose, 240 mg/day of imipramine on a twice-daily (BID) schedule, or placebo for six weeks. Efficacy measurements included HAM-D, MADRS, CGI, Raskin-Covi and SCL-56 scales. The HAM-D total score indicated that both active treatment groups showed significantly (p < or = 0.05) greater therapeutic benefit than did placebo. Severely depressed patients (HAM-D > or = 30) responded better to fluvoxamine in five of six measures. Side-effects from fluvoxamine were similar to those reported for other selective serotonin reuptake inhibitors (nausea, somnolence) and were well tolerated. Imipramine was associated with anticholinergic effects such as dry mouth and dizziness. The pharmacokinetic properties of fluvoxamine which allow the drug to be administered as a single daily dose should aid in the maintenance of patient compliance, while offering significant clinical benefit in the improvement of depressive symptoms.",
"This randomized, double-blind, parallel-group design study of 100 outpatients with major depressive disorder is the first study in the United States to compare the efficacy and tolerability of fluvoxamine (100-150 mg/day) and fluoxetine (20-80 mg/day). After a variable, single-blind, washout period, patients were randomized to receive either fluvoxamine (51 patients) of fluoxetine (49 patients) for 7 weeks. Efficacy was assessed with the 21-item Hamilton Rating Scale for Depression (HAM-D), and Clinical Global Impressions scale for severity and improvement. Eighty-four percent of each treatment group completed the study with each group having a mean score at end point of less than 10. Both groups demonstrated a 60% improvement in HAM-D scores over the 7-week trial. There were no statistically significant differences observed between the two groups on any efficacy parameter. The medications were well tolerated, with only two patients in each group who were terminated because of side effects. There were differences in the side-effect profiles, with fluvoxamine being associated with less nausea than fluoxetine. In summary, fluvoxamine and fluoxetine were equally effective in reducing depressive symptoms, but the two drugs displayed slightly different side-effect profiles.",
"1 We report the results of a comparative clinical trial of a new antidepressant drug fluvoxamine (a specific re-uptake inhibitor of 5-hydroxytryptamine (5-HT)) with chlorimipramine. Thirty-two patients with mixed depression received one or the other drug at the same daily dosage of 150 mg. 2 In both drug groups there was an overall clinically significant improvement for all items on the Hamilton Rating Scale for Depression (67% improvement in both groups). 3 In the chlorimipramine group there were more digestive symptoms and anticholinergic effects; the difference with the fluvoxamine group approached statistical significance. 4 No clinically important effects of either treatment were observed on heart-rate or blood pressure.",
"The authors employed a double-blind, placebo-controlled design to investigate the effectiveness of fluvoxamine versus imipramine in 54 outpatients with moderate major depression. Fluvoxamine proved superior to placebo but not to imipramine on the Hamilton Rating Scale for Depression and the Montgomery and Asberg Depression Rating Scale. Nausea and hyperarousal were the most common side effects in the fluvoxamine-treated patients.",
"The efficacy of fluvoxamine was compared to that of amitriptyline in a double-blind 6-week fixed-dose trial of 56 inpatients with major depressive episode. The two drugs were comparable in their antidepressant efficacy. We tested the percentage of improvement in Hamilton-D scores during the first and the second weeks of treatment as predictors of efficacy for the last week. Improvement rates during the second week significantly predicted the outcome. We also investigated whether or not some symptomatological characteristics would permit prior prediction of the outcome with amitriptyline or fluvoxamine, dividing our sample into responders and nonresponders to the two drugs. The four groups showed differences in their symptomatological profiles.",
"Fluvoxamine, a selective serotonin reuptake inhibitor, was investigated in a 6-week double-blind study among severely ill inpatients with DSM-III major depression. All but 1 patient also fulfilled criteria for melancholia. Following a 3-day placebo wash-out patients were randomly assigned to fluvoxamine, imipramine or placebo. Sixty of 81 patients completed at least 2 weeks following wash-out and were evaluated for efficacy. Analysis of covariance (controlling for baseline scores) showed significant (p less than 0.05) differences on CGI severity and BPRS total and a similar trend (p = 0.08) on the Hamilton Depression Scale. Fluvoxamine was superior (p less than or equal to 0.02) to both placebo and imipramine on these measures. Fluvoxamine's most common adverse effects were nausea and agitation. The number of fluvoxamine patients withdrawn for side-effects was less than imipramine and not significantly different than placebo. Fluvoxamine was not associated with significant changes in vital signs, ECG or laboratory tests. The results therefore indicate that fluvoxamine is a safe and highly effective treatment for hospitalized patients with major depression.",
"The efficacy and tolerability of the selective 5-HT reuptake inhibitor fluvoxamine were compared with the tricyclic dothiepin in 52 elderly (age greater than 64 years) hospital patients in a multi-centre double-blind randomised trial. Patients met DSM-III criteria for 'major depressive episode' and scored greater than 29 on the Montgomery Asberg Depression Rating Scale (MADRS) after a one-week placebo baseline. Active treatment was for six weeks. The dosage of both drugs was 50 mg nocte for three days, 100 mg nocte for the remainder of the first week, thereafter increasing to a maximum of 200 mg/day according to response/tolerance. MADRS scores improved by 63.5% with fluvoxamine and 60.0% with dothiepin; there were no significant differences between treatments at any assessment. Nausea, dizziness, headache, somnolence and constipation in both groups, plus dry mouth and asthenia in the dothiepin group were more frequent than single reports. Two patients in each group discontinued treatment owing to unwanted effects. There were no clinically significant changes in haematological, biochemical or cardiovascular parameters.",
"Previous studies have reported the efficacy of selective serotonin reuptake inhibitors as monotherapy in the treatment of delusional depression. The clinical efficacy of venlafaxine, a serotonin-norepinephrine reuptake blocker, has been demonstrated in the treatment of patients with moderate-to-severe depression, but, to date, no evidence is available about its use in depressed patients with psychotic features.\n Under double-blind conditions, 28 hospitalized patients who met DSM-IV criteria for major depression, severe with psychotic features, were randomly assigned to receive fluvoxamine or venlafaxine, 300 mg/day, for 6 weeks. Severity was evaluated using the Hamilton Rating Scale for Depression (HAM-D) and the Dimensions of Delusional Experience Rating Scale (DDERS) administered at baseline and every week thereafter. Side effects were also recorded. Clinical response was defined as a reduction of the scores in the 21-item HAM-D to 8 or below and in the DDERS to 0.\n At study completion, the response rates were 78.6% (N = 11) and 58.3% (N = 7) for fluvoxamine and venlafaxine, respectively. No significant difference was found between drugs (Fisher exact test, p = .40). Analysis of covariance on HAM-D scores did not reveal a significantly different decrease of depressive symptomatology between the 2 treatment groups (p = .14). Treatment response appeared to be unrelated to the demographic and clinical characteristics recorded. The overall safety profile of both fluvoxamine and venlafaxine was favorable.\n The results of this pilot double-blind trial show that fluvoxamine is useful in the treatment of delusional depression and suggest that venlafaxine may also be an effective compound in the treatment of this disorder. The latter finding, although promising, warrants further replication in a larger sample of patients.",
"1 A double-blind placebo-controlled study of fluvoxamine and imipramine was performed in a group of depressed patients. Twenty-two patients received fluvoxamine (mean dose 101 mg/day), 25 received imipramine (mean dose 127 mg/day) and 22 received placebo. 2 Apart from an increase in the SGOT and SGPT values of four imipramine patients, no statistically significant changes in haematology or urinalysis were judged to be medically relevant. Fluvoxamine exhibited fewer anticholinergic side effects than imipramine. 3 Both fluvoxamine treated patients and imipramine-treated patients exhibited a statistically significant improvement at the end of the 28-day treatment period with respect to the placebo patients, as measured using the Hamilton Rating Scale for Depression, and the Clinical Global Impression Scale. Evaluations of the results of the Beck Depression Inventory and the Profile of Mood States revealed a statistically significant improvement for imipramine patients with respect to placebo at week 4, but not for fluvoxamine patients. It is postulated on the basis of quantitative pharmaco-EEG findings, that the slight superiority of imipramine over fluvoxamine was due to underdosing of the latter.",
"A double-blind, multinational study was conducted to compare the efficacy and safety of fluvoxamine and fluoxetine in outpatients with major depressive episode; 184 patients were randomised to fluvoxamine (100 mg/day) or fluoxetine (20 mg/day) for 6 weeks. Both drugs were effective and there were no statistically significant differences between them in the area under the curve of change from baseline in the Hamilton depression rating scale (HAMD) total score. However, the percentage of HAMD responders (>or= 50% decrease in HAMD total score) at week 2, the clinical global improvement severity of illness score at week 2 and the depression subscale of the irritability, depression and anxiety scale at weeks 1, 2 and 4, all showed significant advantages for fluvoxamine. During the last 2 weeks, fluvoxamine was significantly more effective in improving the HAMD sleep disturbance scale. Both drugs were well tolerated and there were no marked differences in their side effect profiles which were typical of SSRIs. Fluvoxamine and fluoxetine have similar efficacy and safety profiles in the treatment of major depressive episode; the findings of this study indicate that fluvoxamine may have a faster onset of action with respect to resolution of depressive symptoms and result in a better improvement in sleep quality.\n Copyright 2003 John Wiley & Sons, Ltd.",
"The efficacy and safety of fluvoxamine maleate, a selective serotonin reuptake inhibitor, was compared with placebo and imipramine in patients with major depressive disorder. Previous literature has cited a dose range of 100 to 300 mg/day of fluvoxamine maleate for the treatment of major depression; however, this study demonstrates that a dose range of 50 to 150 mg/day is as effective as imipramine (80-240 mg/day). After a 1- to 2-week, single-blind, placebo washout phase, 150 depressed outpatients were randomized to double-blind treatment with fluvoxamine maleate (50-150 mg/day), imipramine (80-240 mg/day), or placebo for 6 weeks. Fluvoxamine produced a significant therapeutic benefit over placebo (p < or = 0.05) as assessed by the total score on the Hamilton Rating Scale for Depression; imipramine (80-240 mg/day) produced similar results. The secondary outcome variables (i.e., Clinical Global Impression severity of illness item and 56-Item Hopkins Symptom Checklist depression factor) also showed significant differences between fluvoxamine maleate and placebo during three of the four final weeks of the study. Both fluvoxamine maleate and imipramine appeared to be safe and well tolerated by the majority of patients. As expected from the pharmacology of these agents, the imipramine groups reported more anticholinergic effects (dry mouth, dizziness, and urinary retention) and electrocardiographic effects, whereas the fluvoxamine group reported more nausea, somnolence, and abnormal ejaculation. The majority of these adverse events were mild to moderate and, with the exception of dry mouth (imipramine) and abnormal ejaculation (fluvoxamine), were transient. The data clearly demonstrate the antidepressant activity and tolerability of fluvoxamine maleate (50-150 mg/day) as compared with placebo; it is also as effective as the tricyclic antidepressant imipramine (80-240 mg/day) in patients with major depressive disorder.",
"In 16 depression clinics in hospitals and outpatient facilities in the Netherlands, a study was performed to evaluate and compare the efficacy and tolerability of citalopram and fluvoxamine and to determine the difference in the incidence of gastrointestinal side-effects. A total of 217 patients with a depressive disorder (DSM-III-R criteria) and a score of at least 16 on the Hamilton rating scale for depression were randomized to treatment. The results of this study indicate that the two drugs are equally effective. The adverse events occurring during treatment show a similar pattern between the two drugs, but citalopram is better tolerated than fluvoxamine. Citalopram induces fewer gastrointestinal adverse events compared with fluvoxamine. However, this did not affect the drop-out rates.",
"The aim of the study was to compare the efficacy and tolerance of fluvoxamine (FL) and amitriptyline (AM) in the treatment of patients hospitalized for moderate and severe depression and to evaluate the spectrum of antidepressive activity in FL. The study was open, randomized and comparative. Sixty patients (mean age 41 +/- 2.9 years) diagnosed as having recurrent depressive disorder, a moderate or severe depressive episode (ICD-10 F33.1, F33.2) were divided into two equal groups treated with FL or AM. The efficacies of FL and AM were comparable, with AM exhibiting an earlier clinical effect and FL having a better tolerance. FL was defined as an antidepressant with the predominantly sedative effect comparable to that of AM, but being better tolerated.",
"Although selective serotonin reuptake inhibitors (SSRIs) are better tolerated than tricyclic antidepressants, their efficacy in severe depression remains to be further elucidated.\n A double-blind, multicentre study was conducted in 86 severely depressed inpatients (>or= 25 on the 17-item Hamilton depression rating scale [HAMD] total score) to compare the efficacy and safety of fluvoxamine with that of clomipramine. Following placebo run-in, 86 patients were randomised to receive fluvoxamine or clomipramine (100-250 mg/day) for 8 weeks.\n Fluvoxamine and clomipramine both resulted in marked improvements; there were no statistically significant differences between them on the 17-item HAMD total score, the clinical global impression severity of illness or global improvement items or the Montgomery-Asberg depression rating scale, at any visit. At the end of the study, 71% in the fluvoxamine group and 69% in the clomipramine group were responders (>or= 50% decrease in 17-item HAMD total score). However, fluvoxamine was better tolerated than clomipramine. Clomipramine was associated with a higher incidence of overall and treatment-related adverse events. In addition, the percentage of patients discontinued prematurely due to adverse events was more than twice as high with clomipramine than with fluvoxamine (24% vs 11%).\n Fluvoxamine and clomipramine are equally effective in severe depression, but fluvoxamine has a better safety and tolerability profile.\n Copyright 2003 John Wiley & Sons, Ltd.",
"Major depression is a common psychiatric disorder in the elderly population. The efficacy of tricyclic antidepressants is well established, and selective serotonin reuptake inhibitors appear to have a similar effectiveness along with advantages in terms of tolerability and safety. Given the lack of literature data regarding fluvoxamine in the treatment of depressed elderly patients, the aim of the present study was to compare its efficacy and tolerability with those of sertraline in a sample of elderly patients.\n Under double-blind conditions, 93 hospitalized patients older than 59 years, who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for a major depressive episode, were randomly assigned to receive sertraline (150 mg daily) or fluvoxamine (200 mg daily) for 7 weeks. The clinical response was defined as a reduction on the Hamilton Rating Scale for Depression score to 8 or below.\n At study completion, the response rates were 55.6% (25/45) and 71.8% (28/39) for sertraline and fluvoxamine, respectively. No significant difference in final response rates was found between the 2 treatment groups (P = 0.12). A repeated-measures analysis of variance on Hamilton Rating Scale for Depression scores revealed a significantly different decrease of depressive symptoms between the 2 treatment groups, favoring fluvoxamine (P = 0.007). The overall safety profile of sertraline and fluvoxamine was favorable with no differences between the 2 drugs.\n The results of this double-blind trial show that sertraline and fluvoxamine may be effective compounds in the treatment of elderly depression with the latter showing some advantage in terms of speed of response. These findings warrant further replication in placebo-controlled studies.",
"In a double blind study performed in psychiatric clinics the efficacy and tolerability of the new antidepressant Moclobemide was compared. Moclobemide belongs to a new class of substances called RIMA (Reversible Inhibitor of the monoamine oxidase type A). 61 patients with major depression (according to DSM-III) were either treated with Moclobemide or Fluvoxamine, a selective reuptake-inhibitor of 5-HT. The latter belongs to a class of antidepressants known for their better tolerability compared to tricyclic antidepressants. Moclobemide was as effective as Fluvoxamine but much better tolerated as shown by a lower incidence of side effects such as gastrointestinal problems or headache.",
"The aim of this study was to compare the efficacy and safety profiles between fluvoxamine and nortriptyline in Japanese patients with major depression.\n The efficacy and safety profiles of fluvoxamine, a selective serotonin-reuptake inhibitor, and nortriptyline were compared under a single-blind fashion in 74 Japanese patients with major depression. The efficacy was assessed using the 17-item Hamilton Rating Scale for Depression (HAM-D), Clinical Global Impression Scale (CGI) severity and improvement scores, while the safety profiles were assessed using the UKU Side Effect Rating Scale at baseline, and on days 7, 14, 28 and 56. Moreover, with the aim of determining the distinct efficacy profiles of each drug, the effects on each of the factor scores extracted by the principal component analysis performed for HAM-D scores were compared between drugs.\n Both drug groups showed significant amelioration of depressive symptomatology over the trial period lasting for 8 weeks. Statistical analyses revealed no significant between-group differences regarding the efficacy assessed by either HAM-D or CGI scores; however, the efficacy of nortriptyline tended to appear earlier than that of fluvoxamine. Moreover, no significant differences were obtained for the factor scores, representing 'depressed mood', 'physical symptoms' or 'sleep disturbances', although 'sleep disturbances' appeared to improve earlier in the nortriptyline group than in the fluvoxamine group. As for the safety profiles, the nortriptyline group scored a significantly higher incidence of adverse events such as dysarthria or orthostatic dizziness, as well as increased heart rate.\n These findings suggest that fluvoxamine is generally comparable to nortriptyline in its efficacy and superior in its safety profile, in accordance with findings obtained in previous comparative clinical trials conducted in Caucasian populations.",
"This is a multicentre double-blind study of fluvoxamine versus mianserin in the treatment of major depressive episode in patients over 65 years of age. Fifty-seven patients received either fluvoxamine (100-200 mg daily) or mianserin (40-80 mg daily). There was no statistically significant difference in improvement between the 2 treatment groups as measured by the Montgomery-Asberg Depression Rating Scale. Eleven patients (7 in the fluvoxamine group and 4 in the mianserin group) discontinued treatment because of intolerance. No statistically significant differences were seen in biological parameters with either drug. Both drugs improved the symptoms of depression though the overall response rate was not outstanding. The side effects profile for the fluvoxamine was contrary to previous studies in that frequent nausea and vomiting were not seen.",
"The efficacy of the selective serotonin reuptake inhibitors (SSRIs) and the tricyclic antidepressants is well established, although data on the efficacy of SSRIs in severe depression is limited. Several studies have demonstrated that fluvoxamine is as effective as clomipramine in the treatment of severe depression. The aim of this four-week study was to compare the efficacy and tolerability of fluvoxamine and clomipramine in hospitalised depressed patients. Patients were eligible for entry into the study if they had an established diagnosis of depression, and an overall score of more than 17 on the first 17-items of the Hamilton Rating Scale for Depression (HAMD). Twenty patients received fluvoxamine 100-300 mg in divided daily doses (mean daily dose 204 mg), and 20 received clomipramine 50-150 mg in divided daily doses (mean daily dose 106 mg) for four weeks. Efficacy was assessed using the HAMD and Clinical Global Impression (CGI) scales, at baseline and weekly intervals thereafter. The investigator's overall rating of efficacy and tolerability was also noted. At the end of the study, both fluvoxamine and clomipramine produced a marked to moderate therapeutic effect. Compared with baseline both fluvoxamine and clomipramine produced similar improvements in the HAMD total, HAMD item and CGI scores. More patients in the clomipramine group experienced anticholinergic side-effects and orthostatic hypotension. Furthermore, a significant difference in favour of fluvoxamine was found with regard to the investigator's overall assessment of undesirable signs and symptoms (p = 0.023; Wilcoxon's test). In conclusion, fluvoxamine is as effective as clomipramine in hospitalised depressed patients, and is better tolerated.",
"Fluvoxamine and paroxetine, both serotonin selective reuptake inhibitors (SSRIs), were compared at two centers in a 7-week double-blind study in outpatients with major depression, diagnosed by DSM-III-R criteria.\n Sixty patients were randomly assigned to receive dosage titrated upward to between 50-150 mg/day of fluvoxamine (N = 30) or 20-50 mg/day of paroxetine (N = 30). The mean +/- SD daily dose administered at the last assessment was 102 +/- 44 mg/day for fluvoxamine and 36 +/- 13 mg/day for paroxetine. Sixteen (53%) fluvoxamine-treated patients and 10 (33%) paroxetine-treated patients were titrated to the maximum permissible dosage of either drug. Sample size was calculated to provide at least 85% power at 5% level of significance to detect at least a 1.00-point difference in mean severity of adverse events, assuming a standard deviation of 1.0.\n Fluvoxamine and paroxetine were similarly effective in ameliorating depression as demonstrated by mean total scores of 10.9 +/- 7.3 (p < .00) and 11.5 +/- 7.4 (p < .00), respectively, in the Hamilton Rating Scale for Depression (HAM-D). Adverse events were mostly mild to moderate in severity. The most common events were headache (N = 17, 57%), nausea (N = 14, 47%), sweating (N = 10, 33%), somnolence (N = 9, 30%), diarrhea (N = 9, 30%), dry mouth (N = 8, 27%), dizziness (N = 8, 27%), and, among males, impotence (N = 3, 21%) and ejaculatory abnormality (N = 3, 21%) in the paroxetine group, and headache (N = 12, 40%), somnolence (N = 12, 40%), nausea (N = 11, 37%), dry mouth (N = 11, 37%), insomnia (N = 9, 30%), asthenia (N = 7, 23%), and dyspepsia (N = 7, 23%) in the fluvoxamine group. The only statistically significant difference between treatment groups was for sweating (33% paroxetine vs. 10% fluvoxamine, p = .028).\n Observed differences in some side effects, although not statistically significant, indicate that when a patient has difficulty tolerating one SSRI, the clinician may choose to change to a different agent within the same class.",
"This study aimed: 1) to compare the analgesic efficacy and profile of two antidepressants with the same mechanism of action (SSRI: selective serotonine reuptake inhibitors): fluoxetine vs fluvoxamine; 2) to investigate the relationship between analgesic efficacy and antidepressant effects in both drugs; 3) to evaluate the relationship between the analgesic profile and the quality (global or neuropathic) of pain.\n Fifty-three depressed patients were randomly treated with 20 mg/die of fluoxetine and 100 mg/die of fluvoxamine for chronic pain. Forty subjects (20 with fluoxetine and 20 with fluvoxamine) completed the 2-month study and were followed up on day 14, 28 and 56 of treatment. The intensity and quality of pain was assessed using Quid and depression-anxiety symptoms with the Hamilton Rating Scale (HAMD).\n The intensity and overall quality of pain deteriorated at day 14 in the fluvoxamine group and improved in those treated with fluoxetine. However, a comparable level of analgesia was achieved with both drugs at 2 months. After 2 weeks the neuropathic component of pain improved in patients treated with fluvoxamine. The improvement in pain observed in patients treated with fluoxetine depended on an improvement in depressive symptoms, whereas this relationship was not observed in the fluvoxamine group.\n Although a comparable level of analgesia was observed after two months of treatment, the two drugs show different analgesic profiles. Their analgesic action appears to depend on different mechanisms.",
"To test the hypothesis that the antidepressant effects of total sleep deprivation (TSD) are linked to the serotonergic and/or noradrenergic system the authors carried out a double-blind study (fluvoxamine versus maprotiline) in 42 inpatients with endogenous depression (ICD). Patients were randomized to a four-week treatment with either fluvoxamine (100-300 mg/day) or maprotiline (100-300 mg/day). In addition, patients underwent a TSD procedure before and after one week of antidepressant medication. There was a statistically significant reduction of depression ratings (HDRS) in both the fluvoxamine and maprotiline group. The day-1 response to TSD before antidepressive medication was not associated with a clear relationship to the outcome after four weeks of treatment with either fluvoxamine or maprotiline. On the other hand, the day-2 response to TSD was significantly correlated with a good outcome to subchronic treatment with maprotiline. Furthermore, the results of the authors' data suggest that a favorable short-term outcome of TSD may be connected to antidepressants enhancing the serotonergic neurotransmission. The global comparison between fluvoxamine and maprotiline revealed that the group of patients treated with fluvoxamine had a significantly higher efficiency index (CGI) than the maprotiline group; fluvoxamine was rated to be tolerated excellently in 70% of the patients whereas this percentage was only 43% in the maprotiline group. There was also significantly more vertigo and dry mouth in the maprotiline group whereas the fluvoxamine group was rated to have significantly more sleep disturbances during the trial.",
"The efficacy and tolerability of moclobemide and fluvoxamine, two new types of antidepressant agents, were compared in a multicentre, double-blind prospective study of patients with a diagnosis of major depressive episode (DSM III). Patients were randomized to receive either moclobemide (150 mg) or fluvoxamine (50 mg) twice daily for 7 days, immediately following a washout period of at least 1 week. Dosages were increased where necessary on day 8, to a maximum of moclobemide 450 mg or fluvoxamine 200 mg and in most cases were maintained at these levels for the remainder of the study period (4-6 weeks). Both treatment groups showed a marked antidepressant effect. While both treatments were well tolerated, moclobemide showed a more favourable side-effect profile than fluvoxamine. Of the 126 patients eligible for evaluation, 34 withdrew from therapy, 22% in the moclobemide group and 30% in the fluvoxamine group. Adverse events were reported in 41.8% of patients treated with moclobemide compared to 60.3% of patients in the fluvoxamine group. Reports of dry mouth and other anticholinergic effects were more frequent among those treated with fluvoxamine. A greater number of gastrointestinal complaints, especially nausea, also occurred in the fluvoxamine-treated patients.",
"A six- to eight-week double-blind placebo-controlled trial of the potent and selective serotonin reuptake inhibitor fluvoxamine was conducted in 42 patients with primary obsessive-compulsive disorder (OCD). Approximately one half of the patients also had symptoms of major depression. Fluvoxamine was significantly better than placebo on all measures of obsessive-compulsive symptoms. Nine of 21 patients were responders (\"much improved\") with fluvoxamine compared with no responders with placebo, and fluvoxamine was effective in patients with OCD both with and without secondary depression. Response of OCD was not correlated with severity of baseline depression. These data lend partial support to the serotonin hypothesis of OCD. However, since a number of patients failed to respond to fluvoxamine, the role of other neurochemical systems in this disorder needs to be explored.",
"Forty patients with a diagnosis of major depressive disorder were entered in a double-blind study to assess comparative clinical response and pharmacologic parameters of fluvoxamine, a highly selective blocker of serotonin reuptake, and desipramine, a noradrenergic agent. Eighteen patients receiving desipramine and 17 patients receiving fluvoxamine completed the study. Fluvoxamine was comparable to desipramine in its antidepressant efficacy and was better tolerated and caused minimal side effects. There was a direct linear relationship between plasma fluvoxamine levels and clinical response and a nonlinear relationship between plasma desipramine levels and clinical response. The pharmacologic specificity of the two drugs was assessed by determining uptake inhibition of serotonin and norepinephrine. The authors found a positive relationship between Hamilton Rating Scale for Depression scores and norepinephrine uptake inhibition for desipramine but found no such relationship between fluvoxamine and serotonin uptake inhibition. Although there was a clear-cut difference in the quality of pharmacologic specificity and a partial relationship to clinical response, the authors were unable to identify neuropharmacologic factors that would predict either treatment response or selective amelioration of symptomatologies in this patient population.",
"To compare the efficacy of imipramine and fluvoxamine in inpatients from two centers suffering from a depressive disorder according to DSM IV criteria.\n The study included 141 patients with a depressive disorder according to DSM IV criteria. After a drug-free and placebo run-in period of 1 week, patients were randomized to imipramine or fluvoxamine; doses of both drugs were adjusted to a predefined target blood level. Efficacy was evaluated 4 weeks after attaining predefined adequate plasma level.\n The mean age of the study group (47 males, 94 females) was 51.8 (range 19-65) years. Of these 141 patients, 56 had episode duration longer than 1 year, 48 had mood congruent psychotic features, and 138 patients received medication. Seven patients did not complete the medication trial. The total number of patients using concurrent medication was 12/138 (8.6%). On the primary outcome criteria patients on imipramine improved significantly better on the change of illness severity score of the CGI (chi2 exact trend test=4.089, df=1, P=-0.048). There was no significant difference in 50% or more reduction on the HRSD, the other primary outcome criterion. On the secondary outcome criteria the mean reduction of the HRSD scores was significantly larger in the imipramine group than in the fluvoxamine group (mean difference=3.1, standard error (SE)=1.4, t=2.15, df=136, P=0.033). There was no significant difference in the number of patients with an HRSD < or =7 at the final evaluation.\n In depressed inpatients imipramine is more efficacious than fluvoxamine. Both drugs were well tolerated by all patients.",
"1. Fluvoxamine is a potent serotonin re-uptake inhibitor, with little or no noradrenergic or anticholinergic activity. 2. The results of three studies using an almost identical protocol with a prospectively randomized, double-blind design comparing fluvoxamine and chlorimipramine are presented. 3. In a population of 98 subjects suffering from a variety of depressive conditions, there was a marked improvement over four weeks in both groups. dosage was maintained between 150 and 300 mg per day. 4. There were no changes of clinical importance in vital signs, hematology or biochemistry, but pulse rates increased in the chlorimipramine group. 5. There were fewer concurrent signs and symptoms in the fluvoxamine group, especially those attributable to anticholinergic activity.",
"The efficacy and CNS effects of the selective 5-HT re-uptake inhibitor fluvoxamine were compared with mianserin in depressed hospital out-patients in a double-blind randomized trial. Patients had to meet DSM-III criteria for Major Depressive Episode and achieve a score of at least 30 on the Montgomery-Asberg Depression Rating Scale (MADRS) after a 1-week placebo baseline period. Active treatment was for 6 weeks with an initial dose of either 100 mg fluvoxamine or 60 mg mianserin; after 1 week the dosage could be increased to 300 mg or 180 mg, respectively. Data from 63 patients (30 received fluvoxamine) were analyzed. The treatment groups were comparable with regard to age and history and severity of depression. Efficacy assessments showed similar improvements with each drug; MADRS scores improved by 65.6% with fluvoxamine and by 60.8% with mianserin. There were no significant differences between treatments at any assessment. Sedative effects were assessed using the Leeds Sleep Evaluation Questionnaire and the Digit Symbol Substitution Test. Mianserin caused a shift towards sedation in the first week in all visual analogue scales; getting to sleep and sleep quality were improved but waking was more difficult than with fluvoxamine. Similarly, the mianserin group performed less well on the Digit Symbol Substitution Test. The study confirmed that both drugs are effective treatments for depressive illness but that mianserin gives rise to sedation during the first week.",
"1 Two double-blind, randomised studies were performed to compare the efficacy of fluvoxamine and chlorimipramine in depressed patients. In the first study the effects of a single daily dosage of between 100 and 300 mg of fluvoxamine were compared with those of chlorimipramine at a dosage of 50-150 mg daily in 43 out-patients with endogenous depression. 2 In a second study using three times daily dosing with a daily dosage of 150-300 mg for both fluvoxamine and chlorimipramine, 30 in-patients with unipolar depression were assessed. 3 Four weeks of treatment with single daily dosing resulted in a mean improvement of 61.4% (+/- s.d. 31.7) on the Hamilton Rating Scale for Depression (HAMD) for fluvoxamine and of 65.3% (+/- s.d. 25.8) for chlorimipramine. In the study with three times daily dosing the mean results were 72.9% (+/- s.d. 22.3) improvement for fluvoxamine and 62.1% (+/- s.d. 28.5) for chlorimipramine. 4 At similar dosages, fluvoxamine had significantly less untoward effects on blood pressure than chlorimipramine. Anticholinergic effects were also fewer in the fluvoxamine group, as were nervous system symptoms, with the latter difference reaching statistical significance (P = 0.02). 5 We conclude that fluvoxamine, given in a single daily dose of 150-250 mg, provides antidepressant efficacy similar to chlorimipramine. At this dosage it may be expected to produce less anticholinergic effects and have less influence on blood pressure than chlorimipramine.",
"The antidepressant efficacy and tolerability of milnacipran, a dual action serotonin-noradrenaline reuptake inhibitor, were compared with those of the selective serotonin reuptake inhibitor, fluvoxamine, in 113 patients with moderate to severe major depression. Treatment with milnacipran, 50 mg b.d. for 6 weeks, produced a significantly greater reduction in Montgomery-Asberg Depression Rating Scale (MADRS) scores than fluvoxamine, 100 mg b.d. (P = 0.007; 65.4% versus 49.9%, respectively); significantly greater decreases were also seen on days 7 (P = 0.04) and 28 (P = 0.03). The response rate (the proportion of patients showing a decrease in MADRS scores of at least 50%) was 78.9% in patients receiving milnacipran, compared with 60.7% in fluvoxamine-treated patients (P = 0.04). Milnacipran also produced greater improvements in 24-item Hamilton Depression Rating Scale scores (P = 0.05). On the Clinical Global Impression Improvement scale, 77.2% of milnacipran-treated patients were rated as considerably or markedly improved, compared with 60.7% of patients receiving fluvoxamine (P = 0.06 chi-squared). Both treatments were well tolerated; the only significant difference between the two groups was a higher incidence of tremor and drowsiness in patients treated with fluvoxamine. It is concluded that milnacipran may offer some advantages over selective serotonin reuptake inhibitors, such as fluvoxamine, in the treatment of moderate to severe major depression.",
"Thirty-eight patients with primary obsessive-compulsive disorder participated in a 10-week, double-blind, placebo-controlled trial of the potent, selective serotonin reuptake inhibitor fluvoxamine. Fluvoxamine was significantly better than placebo on two of three measures of improvement in obsessive-compulsive symptoms. The authors also compared studies of the serotonergic agents fluvoxamine, sertraline, fluoxetine, and clomipramine and found that a greater effect size was associated with less serotonergic specificity and that some ability to affect other neurotransmitter systems may be a necessary but not sufficient requirement for antiobsessional activity. These data lend only partial support to a serotonin hypothesis of obsessive-compulsive disorder.",
"Numerous neuropsychological studies have reported deficits in cognitive and attentional functioning in depressed patients. However, there are limited data available about unmedicated depressed patients and the effects of antidepressant treatment on attentional performance. In this study, a Continuous Performance Test (CPT) was employed to evaluate the attentional performance of depressed inpatients during a drugfree period (n = 52) in comparison to healthy control subjects (n = 73). After 4 weeks of double-blind treatment with imipramine (TCA) or fluvoxamine (SSRI) at adequate plasma levels the CPT performance was studied again. We found that the unmedicated patients had a significantly impaired performance on all CPT parameters (reaction time, omission errors and commission errors) in comparison to the controls. None of the CPT parameters correlated with the severity of the depression or the level of psychomotor retardation. However, the CPT performance in the patient group was significantly related to subjective mood state (depression, tension). Double-blind treatment with imipramine or fluvoxamine resulted in an improvement of the CPT performance. In the imipramine treatment group the mean reaction time decreased significantly, and after treatment with fluvoxamine a significant decrease of the mean reaction time and the number of omission errors was detected. Both antidepressants induced a significant improvement of clinical state, but we did not find a relationship between the altered CPT performance and the changes on the clinical scales. Future studies should investigate other mechanisms underlying the improved attentional performance after treatment.\n Copyright 2002 Elsevier Science Ltd.",
"Fluvoxamine CR has been reported effective in the short-term (12-wk) treatment of generalized social anxiety disorder (social phobia). Social anxiety disorder (SAD) is, however, a chronic disorder thought to require maintenance treatment. We report on data from the extension phase of a short-term study, in order to explore the efficacy and safety profile of fluvoxamine CR (100-300 mg/d) in the longer-term treatment of this disorder. Adult outpatients with generalized social anxiety disorder (GSAD) at 35 centres in Europe, South Africa, and USA were included in an acute phase study (12 wk). Subjects who demonstrated at least minimal improvement by endpoint (n=112), were offered participation in an extension phase, in which medication was continued for a further 12 wk under double-blind conditions. Efficacy was assessed using the Liebowitz Social Anxiety Disorder Scale (LSAS), the Clinical Global Impression Global Improvement score (CGI-I), the Clinical Global Impressions Severity of Illness score (CGI-S), and the Sheehan Disability Scale (SDS). Safety and tolerability assessments were also performed at regular intervals. Subjects treated with fluvoxamine CR had a numerically greater decrease in LSAS total scores than subjects treated with placebo at endpoint. Analysis of data from baseline (day 1) to endpoint (last observation carried forward) demonstrated that this difference tended towards significance, while severity of illness on the CGI-S and disability on the SDS were significantly lower in the fluvoxamine CR group than in the placebo group. The same trends were observed when only data from weeks 12-24 were included in the analysis; although the magnitude of changes was smaller in the extension phase than in the acute phase, fluvoxamine CR-treated subjects continued to show improvement compared to placebo-treated subjects. Most treatment-emergent signs and symptoms (TESS) were mild to moderate in severity. No unexpected abnormalities were reported on vital signs, electrocardiagrams, or laboratory investigations. These data support the long-term efficacy, safety, and tolerability of fluvoxamine CR in the treatment of GSAD. Given the prevalence, persistence, and disability associated with GSAD, and the relative paucity of long-term treatment studies of SAD, the current dataset provides empirical support for the current clinical consensus that pharmacotherapy of this disorder should be continued beyond the acute phase.",
"The aim of this 12-week, double-blind, flexible-dose, placebo-controlled, parallel-arm, multicenter trial was to determine the safety and efficacy of fluvoxamine in a controlled-release (CR) formulation in adult outpatients with obsessive-compulsive disorder (OCD).\n 253 adult outpatients with DSM-IV OCD were randomly assigned to receive 100 to 300 mg of fluvoxamine CR (N = 127) or placebo (N = 126) once daily for 12 weeks. Intent-to-treat analyses of efficacy assessments with the Yale-Brown Obsessive Compulsive Scale (YBOCS), Clinical Global Impressions-Severity of Illness scale (CGI-S), and Clinical Global Impressions-Improvement scale (CGI-I) were conducted.\n Fluvoxamine CR was significantly (p <.05) superior to placebo in decreasing YBOCS total score beginning at week 2. This early response was sustained at all subsequent visits. At endpoint, there was a mean decrease of 8.5 +/- 0.7 (31.7%) in the YBOCS total score compared with baseline in the fluvoxamine CR treatment group versus a mean decrease of 5.6 +/- 0.7 (21.2%) in the placebo group (p =.001). Fluvoxamine CR was also significantly superior to placebo in lowering the severity of illness (CGI-S, p =.002) and in producing clinical improvement (CGI-I, p <.01). At endpoint, significantly greater percentages of the fluvoxamine CR treatment group were responders (p =.002) and remitters (p =.019) compared with the placebo group.\n Over 12 weeks, fluvoxamine CR treatment was associated with a statistically significant and clinically relevant reduction in OCD severity and was found to be safe and well tolerated. The early onset of therapeutic effect, starting from week 2, was of particular interest.",
"Fluoxetine is the first selective serotonin reuptake inhibitor antidepressant to be marketed in the U.S. In this double-blind trial fluoxetine was compared with imipramine and placebo among 198 outpatients with DSM-III major depression, of whom 145 completed at least 2 weeks of active treatment and were evaluated for efficacy. Significantly fewer patients in each active drug group terminated early due to lack of efficacy compared to placebo. Both imipramine and fluoxetine were significantly superior to placebo on most measures. There were no consistently significant differences between the two active drugs although a trend favored imipramine on a number of measures. Fluoxetine was generally well tolerated. Significantly more imipramine than placebo patients terminated early due to side-effects while the fluoxetine-placebo difference was not significant. The results support previous studies which suggest fluoxetine's superior side-effect profile and the approximate antidepressant equivalence of fluoxetine and TCAs.",
"One hundred and eighty three patients with DSM-III-R major depressive illness were allocated randomly to treatment with one of two new generation antidepressants, fluoxetine and lofepramine. Both patient groups had significantly lower mean scores on the Hamilton Depression Rating Scale (HDRS) 6 weeks after entry to the trial (p < 0.001), but there were no differences between the groups, either at baseline or after 6 weeks, in total HRDS score or in subscores for anxiety or suicidality. Anticholinergic side effects were commoner with lofepramine; adverse effects were on the whole mild and few patients dropped out because of them. This study does not support previous claims of specific adverse effects of fluoxetine on anxiety and suicidality.",
"Depression is an international public health problem. Impairment in social and occupational functioning, increased comorbidity with other psychiatric and medical conditions, and an increased risk of mortality are a few of its consequences. Some psychiatrists have the impression that selective serotonin re-uptake inhibitors may not work as well as tricyclic anti-depressants in severe depression and/or melancholia. On the contrary, there is a general belief that selective serotonin re-uptake inhibitors are superior to the tricyclic anti-depressants in having fewer side-effects, particularly cardiovascular effects. The objective of this double-blind study was to compare the efficacy and safety of fluoxetine and nortriptyline in patients with moderate to severe major depression.\n A total of 48 adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders (DSM IV), forth edition for major depression, based on the structured clinical interview for DSM IV participated in the trial. Patients had a baseline Hamilton Rating Scale for Depression score of at least 20. In this double-blind, single-center trial, patients were randomly assigned to receive nortriptyline 150 mg/day (group 1) or fluoxetine 60 mg/day (group 2) for 6-weeks. The outcome of the two groups was assessed using Hamilton Depression Rating Scale, a side-effect checklist and a regular ECG assessment.\n The results suggest that the efficacy of nortriptyline is superior to fluoxetine in this group of major depressed patients. No significant differences were observed between dropout rates in the two groups but anti-cholinergic side-effects were significantly more frequent with nortriptyline than with fluoxetine but there was no significant difference in cardiovascular effects in particular QTc prolongation.\n The results of the current study suggest that nortriptyline was more effective than fluoxetine in the treatment of moderate to severe depression. A larger study is warranted.",
"We investigated the relationships between the changes in plasma catecholamine metabolites obtained from depressed patients before and after administration of sulpiride, a benzamide compound, or fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), and between clinical responses to treatment with each of these drugs. Responders to sulpiride had significantly lower plasma homovanillic acid (pHVA) levels before administration of sulpiride than did non-responders or controls (responders: 4.5 +/- 3.1 ng/ml, non-responders: 11.1 +/- 5.9 ng/ml, controls: 10.9 +/- 5.3 ng/ml). Positive relationships were observed between changes in pHVA levels and improvement rates in the 17-item Hamilton Depression Rating Scale (Ham-D). In contrast, responders to fluvoxamine had significantly higher plasma free 3-methoxy-4-hydroxyphenylglycol (pMHPG) levels before administration of fluvoxamine than did non-responders or controls (responders: 8.5 +/- 1.8 ng/ml, non-responders: 5.9 +/- 2.I ng/ml, controls: 5.2 +/- 2.9 ng/ml). Negative relationships were observed between changes in pMHPG levels and improvement rates in Ham-D. These results suggest that lower pretreatment pHVA levels and higher pretreatment levels of pMHPG might be predictors of response to sulpiride and fluvoxamine, respectively, and that sulpiride might produce a functional increase in the dopaminergic system, resulting in improvement in some depressive symptoms; fluvoxamine, on the other hand, might produce a functional decrease in the noradrenergic system via serotonergic neurons, resulting in improvement of those symptoms.",
"A common presentation for major depression includes psychomotor agitation. However, this subtype has been the infrequent subject of controlled investigation during depression trials. Yet, the subcategorization of agitated depression has historically been associated with the belief that older, sedating compounds have a superior risk:benefit profile. In the 8-week, double-blind, randomized, parallel trial, 124 subjects with Research Diagnostic Criteria-compatible agitated depression were randomized to either imipramine (IMI) or fluoxetine (FLU). Both compounds proved to be similarly effective as measured by change in HAM-D17, HAM-D17 response, and HAM-D17 remission rates. Similar comparability was seen in secondary measures of agitation, anxiety, suicidality, and global impressions. However, of note, a statistically significant difference in early discontinuations because of intolerable adverse events emerged. Whereas 43.5% of IMI subjects discontinued early, only 9.7% of FLU subjects (p < 0.001) did. Significantly more central nervous system events characterized the IMI than the FLU subgroup (IMI, 24.2%, vs. FLU, 6.5%; p = 0.006). In conclusion, among subjects with major depression, subtype agitated, the risk:benefit profile favored FLU over IMI. This was driven by the superior tolerance of FLU. No evidence emerged in support of the clinical hypothesis that a \"sedating\" agent is the treatment of choice for this group. The results are important when striving to maximize compliance with pharmacotherapy in order to minimize recidivism and associated psychological and economic morbidity.",
"The antidepressant efficacy and short-term safety of venlafaxine and fluoxetine were compared in 68 patients hospitalized with major depression and melancholia. Venlafaxine was superior in efficacy to fluoxetine; total scores for both the MADRS and the HAM-D were significantly (p < or = 0.05) lower in the venlafaxine group than in the fluoxetine group at Weeks 4 and 6. Overall tolerance was similar for the two treatments."
] |
We found no strong evidence that fluvoxamine was either superior or inferior to any other antidepressants in terms of efficacy and tolerability in the acute phase treatment of depression. However, differing side effect profiles were evident. Based on these findings, we conclude that clinicians should focus on practical or clinically relevant considerations, including these differences in side effect profiles.
|
CD003223
|
[
"3531953",
"3288258"
] |
[
"Analgetic activity of calcitonin in patients with painful osteolytic metastases of breast cancer. Results of a controlled randomized study.",
"Evaluation of salmon calcitonin treatment in bone metastases from breast cancer--a controlled trial."
] |
[
"The analgesic effect of salmon calcitonin was tested by a double-blind clinical randomized controlled trial in 40 female patients with painful osteolytic metastases. Twenty patients were administered (daily) 100 IU of salmon calcitonin subcutaneously over 28 days, while the other 20 were administered identical ampoules containing 2 ml of physiological solution over the same period of time. The basic treatment (chemotherapy, hormone therapy) was not changed during the trial, and had to be stabilized for a minimum of 3 months prior to the trial. The effect of calcitonin was monitored with respect to daily analgesic consumption, duration of pain, patient's functional capacity, patient's own assessment of pain, and assessment of efficacy by the investigator. Statistically significant differences were established in terms of reduced analgesic consumption, shorter duration of pain and the patient's subjective assessment of pain duration and intensity; the difference was not statistically significant with regard to patient's functional capacity. The objective assessment of the analgesic effect of calcitonin by the investigator showed the drug to be extremely useful in 3 patients and moderately useful in 11 patients; 3 instances of 'moderately useful' were observed in the placebo group. No changes were observed in serum calcium levels; there were likewise no skeleton changes as established by X-rays and bone scintiscans before and at the end of treatment. The trial has shown calcitonin to produce a pronounced analgesic effect in breast cancer patients with painful osteolytic metastases.",
"Salmon calcitonin 100 MRCU/day or a saline placebo were given in daily injections for at least three months to 49 patients with bone metastases from breast cancer in a randomized double-blind trial. All patients were normocalcemic, and most patients had stable or regressing disease at start of trial. No improvement in general performance or bone pain was detected as measured by a visual analogue scale, the daily duration of pain or consumption of analgetic drugs. Calcitonin had no effect on disease progression as judged by bone scans and radiographs. Calcitonin therapy did not affect serum calcium, alkaline phosphatase, bone gla-protein, or the urinary excretion of calcium and hydroxyproline. Serum phosphate and magnesium decreased significantly during calcitonin treatment (p = 0.01, and 0.00005, respectively). It was concluded that salmon calcitonin in this dosage has no discernible effect on skeletal pain, general performance, bone metabolism or disease progression in patients with breast cancer metastatic to bone. A significant decrease in serum phosphate and magnesium probably indicated an effect of calcitonin on the renal excretion of these ions."
] |
The limited evidence currently available does not support the use of calcitonin to control pain from bone metastases. Since the last version of this review, none of the new relevant studies have provided additional information on this treatment, in contrast to other therapeutic approaches that should be considered.
|
CD004866
|
[
"8694013",
"21402642"
] |
[
"Randomized outcome trial of human milk fortification and developmental outcome in preterm infants.",
"Nutrient enrichment of mother's milk and growth of very preterm infants after hospital discharge."
] |
[
"Despite potential benefits, human milk may fail to meet preterm infants' nutrient requirements. We tested the hypothesis that fortified breast milk, fed alone or with preterm formula, would improve neurodevelopment and growth at 18-mo follow-up without adverse short-term clinical or biochemical consequences. Two hundred seventy-five preterm infants from two medical centers (birth weight < 1850 g; mean gestation 29.8 +/- 2.7 wk) whose mothers chose to provide breast milk were randomly assigned to receive for a mean of 39 d a multinutrient fortifier or control supplement containing phosphate and vitamins. Breast milk comprised 47.6% and 46.4% of enteral intake in fortified and control groups, respectively; preterm formula supplements were used when insufficient breast milk was available. Overall, there were no significant growth advantages with fortification; although, when breast milk exceeded 50% of intake, fortification promoted faster weight gain (an advantage of 1.6 g.kg-1.d-1; 95% CI: 0.1, 3.1; P < 0.05). Compared with control infants, the fortified group showed 1) higher plasma urea from week 2 (P = 0.04), 2) higher plasma calcium (mean 2.34 +/- 0.01 compared with 2.27 +/- 0.02 mmol/L; P = 0.003), 3) a greater rise in alkaline phosphatase by week 6 (P = 0.04), 4) more clinical infections (suspected plus proven; 43% compared with 31%, P = 0.04), 5) a nonsignificantly increased incidence of necrotizing enterocolitis (5.8% compared with 2.2%, P = 0.12), and 6) higher white cell and platelet counts. Developmental scores at 18 mo were slightly but not significantly higher in the fortified group. This study confirmed that breast milk fortifiers can improve short-term growth (when breast milk intakes are high); but beneficial effects on long-term development remained unproven. Future research is required to evaluate potential adverse consequences and explore more optimal fortification strategies.",
"To determine if the addition of a multinutrient human milk fortifier to mother's milk while breastfeeding very preterm infants after hospital discharge is possible and whether it influences first-year growth.\n Of a cohort of 320 infants (gestational age: 24-32 weeks; birth weight: 535-2255 g), breastfed infants (65% [n = 207]) were randomly assigned shortly before hospital discharge to receive either unfortified (n = 102, group A) or fortified (n = 105, group B) mother's milk until 4 months' corrected age (CA). The remaining infants were bottle-fed with a preterm formula (group C). Follow-up was performed at term and at 2, 4, 6, and 12 months' CA.\n Mean duration of breastfeeding after term was not significantly different between groups A and B (11.8 and 10.6 weeks, respectively). Weight, length, and head circumference were not significantly different between groups A and B at 12 months' CA. Compared with groups A and B, infants in group C had a higher increase in weight z score until term and in length z score until 6 months' CA. At 12 months' CA, boys in group C were significantly longer and heavier compared with those in groups A and B, whereas girls in group C were longer and heavier compared with those in group A only. A higher protein intake was related to a higher serum urea nitrogen level and growth.\n Fortification of mother's milk after hospital discharge while breastfeeding very preterm infants was possible without influencing breastfeeding duration but did not significantly influence growth parameters at 1 year of age compared with unfortified mother's milk."
] |
The limited available data do not provide convincing evidence that feeding preterm infants with multinutrient fortified breast milk compared with unfortified breast milk following hospital discharge affects important outcomes including growth rates during infancy. There are no data on long-term growth. Since fortifying breast milk for infants fed directly from the breast is logistically difficult and has the potential to interfere with breast feeding, it is important to determine if mothers would support further trials of this intervention.
|
CD001841
|
[
"9752816",
"10972367",
"10972368",
"2892881",
"1638340",
"2296269",
"7508066",
"9383135",
"11759645",
"14660997"
] |
[
"Influences of educational interventions and adverse news about calcium-channel blockers on first-line prescribing of antihypertensive drugs to elderly people in British Columbia.",
"Randomised trial of effects of calcium antagonists compared with diuretics and beta-blockers on cardiovascular morbidity and mortality in hypertension: the Nordic Diltiazem (NORDIL) study.",
"Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT).",
"Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial.",
"Thiazide treatment for calcium urolithiasis in patients with idiopathic hypercalciuria.",
"Thiazide diuretic agents and the incidence of hip fracture.",
"Randomized prospective study of a nonthiazide diuretic, indapamide, in preventing calcium stone recurrences.",
"A computerized intervention to decrease the use of calcium channel blockers in hypertension.",
"A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure.",
"Quality of care for secondary prevention for patients with coronary heart disease: results of the Hastening the Effective Application of Research through Technology (HEART) trial."
] |
[
"The way in which dissemination of evidence changes medical practice needs to be better understood. Controversy about calcium-channel blockers (CCB) in the past 3 years has provided a natural experiment, enabling assessment of the impact of media stories, a national warning letter, a teleconference, small group workshops, and newsletters on first-line prescribing of antihypertensive drugs.\n We included all physicians (4403) in British Columbia who prescribed a thiazide diuretic, beta-blocker, inhibitor of angiotensin-converting enzyme (ACE), or CCB as the first antihypertensive agent for 36,507 residents aged 66 years and over, with no previous or concurrent sign of underlying cardiovascular disease. We used a database covering all prescriptions to elderly people to measure the change in proportion of newly treated patients who received each class of drug as first-line therapy. We used a matched cohort design for assessment of the teleconference and workshops, a randomised community design for the newsletters, and time-series analysis for the media impacts.\n The proportion of patients who received a CCB as first-line therapy declined gradually from 22% in early 1994 to 15% in late 1996. This proportion was not affected by two waves of adverse news about CCBs in 1995, but fell by 5% for 5 months and by 3% for 1 month after two waves in 1996. The proportion of patients who received either a CCB or an ACE inhibitor as first-line therapy, contrary to guidelines, was still 42% overall in 1996. The workshops and newsletters were followed by shifts from first-line CCB to first-line thiazide prescribing.\n Changes in prescribing practices occur gradually with the accumulation of small impacts from educational interventions and lay media attention.",
"Calcium antagonists are a first-line treatment for hypertension. The effectiveness of diltiazem, a non-dihydropyridine calcium antagonist, in reducing cardiovascular morbidity or mortality is unclear. We compared the effects of diltiazem with that of diuretics, beta-blockers, or both on cardiovascular morbidity and mortality in hypertensive patients.\n In a prospective, randomised, open, blinded endpoint study, we enrolled 10,881 patients, aged 50-74 years, at health centres in Norway and Sweden, who had diastolic blood pressure of 100 mm Hg or more. We randomly assigned patients diltiazem, or diuretics, beta-blockers, or both. The combined primary endpoint was fatal and non-fatal stroke, myocardial infarction, and other cardiovascular death. Analysis was done by intention to treat.\n Systolic and diastolic blood pressure were lowered effectively in the diltiazem and diuretic and beta-blocker groups (reduction 20.3/18.7 vs 23.3/18.7 mm Hg; difference in systolic reduction p<0.001). A primary endpoint occurred in 403 patients in the diltiazem group and in 400 in the diuretic and beta-blocker group (16.6 vs 16.2 events per 1000 patient-years; relative risk 1.00 [95% CI 0.87-1.15], p=0.97). Fatal and non-fatal stroke occurred in 159 patients in the diltiazem group and in 196 in the diuretic and beta-blocker group (6.4 vs 7.9 events per 1000 patient-years; 0.80 [0.65-0.99], p=0.04) and fatal and non-fatal myocardial infarction in 183 and 157 patients (7.4 vs 6.3 events per 1000 patient-years; 1.16 [0.94-1.44], p=0.17).\n Diltiazem was as effective as treatment based on diuretics, beta-blockers, or both in preventing the combined primary endpoint of all stroke, myocardial infarction, and other cardiovascular death.",
"The efficacy of antihypertensive drugs newer than diuretics and beta-blockers has not been established. We compared the effects of the calcium-channel blocker nifedipine once daily with the diuretic combination co-amilozide on cardiovascular mortality and morbidity in high-risk patients with hypertension.\n We did a prospective, randomised, double-blind trial in Europe and Israel in 6321 patients aged 55-80 years with hypertension (blood pressure > or = 150/95 mm Hg, or > or = 160 mm Hg systolic). Patients had at least one additional cardiovascular risk factor. We randomly assigned patients nifedipine 30 mg in a long-acting gastrointestinal-transport-system (GITS) formulation (n=3157), or co-amilozide (hydrochlorothiazide 25 mg [corrected] plus amiloride 2.5 mg; n=3164). Dose titration was by dose doubling, and addition of atenolol 25-50 mg or enalapril 5-10 mg. The primary outcome was cardiovascular death, myocardial infarction, heart failure, or stroke. Analysis was done by intention to treat.\n Primary outcomes occurred in 200 (6.3%) patients in the nifedipine group and in 182 (5.8%) in the co-amilozide group (18.2 vs 16.5 events per 1000 patient-years; relative risk 1.10 [95% CI 0.91-1.34], p=0.35). Overall mean blood pressure fell from 173/99 mm Hg (SD 14/8) to 138/82 mm Hg (12/7). There was an 8% excess of withdrawals from the nifedipine group because of peripheral oedema (725 vs 518, p<0.0001), but serious adverse events were more frequent in the co-amilozide group (880 vs 796, p=0.02). Deaths were mainly non-vascular (nifedipine 176 vs co-amilozide 172; p=0.81). 80% of the primary events occurred in patients receiving randomised treatment (157 nifedipine, 147 co-amilozide, difference 0.33% [-0.7 to 1.4]).\n Nifedipine once daily and co-amilozide were equally effective in preventing overall cardiovascular or cerebrovascular complications. The choice of drug can be decided by tolerability and blood-pressure response rather than long-term safety or efficacy.",
"Men aged 40-64 years with mild to moderate hypertension [diastolic blood pressure (DBP) 100-130 mmHg] were randomized to treatment with a diuretic (n = 3272) or a beta-blocker (n = 3297), with additional drugs if necessary, to determine whether a beta-blocker based treatment differs from thiazide diuretic based treatment with regard to the prevention of coronary heart disease (CHD) events and death. Patients with previous CHD, stroke or other serious diseases, or with contraindications to diuretics or beta-blockers were excluded. If normotension (DBP less than 95 mmHg) was not achieved by monotherapy, other antihypertensive drugs were added, but the two basic drugs were not crossed over. Patients were assessed at 6-monthly intervals. The mean follow-up for end-points was 45.1 months. Blood pressure (BP) side effects and end-points were recorded in a standardized manner. Entry characteristics and the BP reduction achieved were very similar in both treatment groups. All analyses were made on an intention-to-treat basis. The incidence of CHD did not differ between the two treatment groups. The incidence of fatal stroke tended to be lower in the beta-blocker treated group than in the diuretic treated group. Total mortality and the total number of end-points were similar in both groups. The percentage of patients withdrawn due to side effects was similar, whereas the number of reported symptoms, according to a questionnaire, was higher for patients on beta-blockers. The incidence of diabetes did not differ between the two groups. Subgroup analyses did not detect a difference in the effect of beta-blockers compared with diuretics in smokers as opposed to non-smokers, and beta-blockers also had the same effects as diuretics in the quartile with the highest predicted risk for CHD. Beta-blockers and thiazide diuretics were approximately equally well tolerated. The two drugs had a similar BP reducing effect although additional drugs had to be given more often in the diuretic group. Antihypertensive treatment based on a beta-blocker or on a thiazide diuretic could not be shown to affect the prevention of hypertensive complications, including CHD, to a different extent.",
"In a randomised trial based on a parallel design to determine the prophylactic effect of thiazide on stone formation, 210 calcium urolithiasis patients with idiopathic hypercalciuria were allocated either to treatment with trichlormethiazide (4 mg/day) or no treatment with only close follow-up; 35 patients were excluded for various reasons, including voluntary withdrawal. The background of the remaining 175 patients (82 in the thiazide group and 93 in the control group), including age and sex, was similar for both groups. In patients treated with thiazide there was a statistically significant fall in urinary calcium output. Statistical analyses also demonstrated that the stone formation rate in the thiazide group was significantly less than that in the control group. Adverse clinical reactions probably due to the drug were observed in 9 patients. These findings indicate that trichlormethiazide has a prophylactic effect on calcium urolithiasis in patients with idiopathic hypercalciuria.",
"Thiazide diuretic agents lower the urinary excretion of calcium. Their use has been associated with increased bone density, but their role in preventing hip fracture has not been established. We prospectively studied the effect of thiazide diuretic agents on the incidence of hip fracture among 9518 men and women 65 years of age or older residing in three communities. At base line, 24 to 30 percent of the subjects were thiazide users. In the subsequent four years, 242 subjects had hip fractures. The incidence rates of hip fracture were lower among thiazide users than nonusers in each community; the Mantel-Haenszel relative risk of hip fracture, adjusted for community and age, was 0.63 (95 percent confidence interval, 0.46 to 0.86). The protective effect of the use of thiazides was independent of sex, age, impaired mobility, body-mass index, and current and former smoking status; the multivariate adjusted relative risk of hip fracture was 0.68 (95 percent confidence interval, 0.49 to 0.94). Furthermore, the protective effect was specific to thiazide diuretic agents, since there was no association between the use of antihypertensive medications other than thiazides and the risk of hip fracture. These prospective data suggest that in older men and women the use of thiazide diuretic agents is associated with a reduction of approximately one third in the risk of hip fracture.",
"We examined the biochemical changes and the efficacy of indapamide in the prevention of calcium stone recurrences. Seventy-five patients with calcium nephrolithiasis and hypercalciuria were randomly assigned to three different therapies: diet and fluid (group A), diet and fluid plus indapamide 2.5 mg/day (group B), and diet and fluid plus indapamide 2.5 mg/day plus allopurinol 300 mg/day (group C). Before treatment and after 6, 12, 24, and 36 months of therapy, we evaluated blood pressure, serum and urine risk parameters (including relative supersaturations of calcium oxalate, calcium phosphate and uric acid), stone rate, and the proportion of calculi-free patients. During the 3 years of treatment, urinary calcium greatly decreased in groups B and C, dropping to 50% of the pretreatment values; urinary oxalate also significantly declined in group B (-24%) and group C (-27%). Relative supersaturations of calcium oxalate and calcium phosphate decreased to the same extent in groups B and C (about one-half of the pretreatment value), and relative supersaturation of uric acid was particularly reduced in group C (-65% of the pretreatment value). The stone rate improved in all three groups (p < 0.005), but using actuarial analysis in the evaluation of calculi-free patients, indapamide, and indapamide plus allopurinol groups were found to have a significantly more favorable effect than diet and fluid treatment (p < 0.02), without any difference between the two drug groups. Because indapamide has fewer side effects than thiazide diuretics, we conclude that indapamide could be an interesting alternative to thiazides in the prevention of calcium stones in hypercalciuric patients.",
"To determine whether a computer-assisted reminder would alter prescribing habits for the treatment of hypertension in accordance with current clinical guidelines in a general internal medicine clinic.\n A randomized trial.\n The General Internal Medicine Clinic of the Veterans Affairs Puget Sound Health Care System, Seattle Division.\n Clinic providers were randomized to a control group (n = 35) or intervention group (n = 36). We targeted the providers of patients being treated for hypertension with calcium channel blockers, a class of drug not recommended for initial therapy.\n An automated computer query identified eligible patients and their providers. A guideline reminder was placed in the charts of patients of intervention providers; the charts of patients of control providers received no reminder.\n During the 5-month study period, 346 patients were seen by the 36 primary care providers (staff physicians, nurse practitioners, residents, and fellows) in the intervention group, and 373 patients were seen by the 35 providers in the control group. Intervention providers changed 39 patients (11.3%) to other medications during the study period, compared with 1 patient (<1.0%) of control providers (p < .0001). For patients whose therapy was unchanged, providers noted angina in 23.1%, indications other than those for hypertension in 9.5%, intolerable adverse effects with first-line therapy in 13.9%, and inadequate control with first-line therapy in 13.9%. Of those patients without provider-indicated contraindications, 23.6% were switched from calcium channel blockers to first-line agents during the intervention period.\n The use of a computerized, clinic-based intervention increased compliance with guidelines in the treatment of primary hypertension in general, and decreased the use of calcium channel blockers for the treatment of hypertension in particular.",
"Actions of angiotensin II may contribute to the progression of heart failure despite treatment with currently recommended drugs. We therefore evaluated the long-term effects of the addition of the angiotensin-receptor blocker valsartan to standard therapy for heart failure.\n A total of 5010 patients with heart failure of New York Heart Association (NYHA) class II, III, or IV were randomly assigned to receive 160 mg of valsartan or placebo twice daily. The primary outcomes were mortality and the combined end point of mortality and morbidity, defined as the incidence of cardiac arrest with resuscitation, hospitalization for heart failure, or receipt of intravenous inotropic or vasodilator therapy for at least four hours.\n Overall mortality was similar in the two groups. The incidence of the combined end point, however, was 13.2 percent lower with valsartan than with placebo (relative risk, 0.87; 97.5 percent confidence interval, 0.77 to 0.97; P=0.009), predominantly because of a lower number of patients hospitalized for heart failure; 455 (18.2 percent) in the placebo group and 346 (13.8 percent) in the valsartan group (P<0.001). Treatment with valsartan also resulted in significant improvements in NYHA class, ejection fraction, signs and symptoms of heart failure, and quality of life as compared with placebo (P<0.01). In a post hoc analysis of the combined end point and mortality in subgroups defined according to base-line treatment with angiotensin-converting-enzyme (ACE) inhibitors or beta-blockers, valsartan had a favorable effect in patients receiving neither or one of these types of drugs but an adverse effect in patients receiving both types of drugs.\n Valsartan significantly reduces the combined end point of mortality and morbidity and improves clinical signs and symptoms in patients with heart failure, when added to prescribed therapy. However, the post hoc observation of an adverse effect on mortality and morbidity in the subgroup receiving valsartan, an ACE inhibitor, and a beta-blocker raises concern about the potential safety of this specific combination.",
"Effective therapies for reducing mortality rates in persons with coronary heart disease (CHD) remain underused. We report the results of an effectiveness trial of a quality improvement effort to increase the use of 3-hydroxy-3methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, beta-blockers, and angiotensin-converting enzyme (ACE) inhibitors in patients with CHD in a network-model managed-care setting.\n Patients with CHD were identified by searching a claims database. The use of therapies was assessed by linkage with a pharmacy database. An intervention, consisting of a guideline summary, peer comparison performance feedback, and patient specific chart reminders was evaluated in a randomized, practice-based effectiveness trial.\n Data were available for >700 patients per year (1999-2002) in 131 practices. At baseline (1999), 55% of patients were receiving HMG CoA reductase inhibitors, 39% of patients were receiving beta-blockers, and 24% of patients were receiving ACE inhibitors. The use of all 3 types of medications increased steadily with time, with the exception of a decrease in the use of HMG CoA reductase inhibitors in the final year (2002). No difference in medication use was observed between randomized groups.\n The observed pattern of care supports the contention that the quality of outpatient care for secondary prevention of CHD improved from 1999 to 2002 in this setting. The basis for the inconsistent pattern of use of HMG CoA reductase inhibitors is not certain, but may relate to concerns about toxicity. Centralized mailings of guideline summaries, performance feedback reports, and chart reminders had no observable impact on quality of care in this setting. More intensive intervention may be required to improve the quality of outpatient care for the secondary prevention of CHD."
] |
First-line low-dose thiazides reduce all morbidity and mortality outcomes. First-line ACE inhibitors and calcium channel blockers may be similarly effective but the evidence is less robust. First-line high-dose thiazides and first-line beta-blockers are inferior to first-line low-dose thiazides.
|
CD003827
|
[
"11025176",
"12244905",
"9403542",
"16230723"
] |
[
"Evaluation of antiseptic-impregnated central venous catheters for prevention of catheter-related infection in intensive care unit patients.",
"What really affects the incidence of central venous catheter-related infections for short-term catheterization?",
"A prospective randomized trial of an antibiotic- and antiseptic-coated central venous catheter in the prevention of catheter-related infections.",
"Effect of a second-generation venous catheter impregnated with chlorhexidine and silver sulfadiazine on central catheter-related infections: a randomized, controlled trial."
] |
[
"Central venous catheterization represents a significant medical advancement, particularly in the treatment of critical ill. However, there is a high risk of central venous catheters-related infection. A novel antiseptic central venous catheter, made of polyurethane and impregnated with chlorhexidine and silver sulfadiazine, was developed to reduce the risk of catheters-related infection. In this study, we did a randomized clinical study to determine the efficacy by using antiseptic catheters for the prevention of central venous catheters-related infection in the intensive care units. A total of 204 patients with 235 central venous catheters were studied at the surgical intensive care units at National Taiwan University Hospital between November 1998 and June 1999. Participants received either a standard triple-lumen polyurethane catheter or an antiseptic catheter (Arrow International, Reading, Pennsylvania, USA). Both were indistinguishable from each other. Compared to standard polyurethane catheters, antiseptic catheters were less likely to be colonized by microorganisms when they were cultured at the removal (8.0 versus 20.0 colonized catheters per 100 catheters; relative risk 0.34 [95% CI, 0.15 to 0.74]; p<0.01). There was no significant differences between both groups in catheter-related infections (0.9 versus 4.9 infections per 100 catheters; relative risk 0.17 [95% CI, 0.03 to 1.15]; p = 0.07). Gram-positive cocci and fungi were more likely to colonize in the standard polyurethane catheters (p = 0.06 and 0.04, compared to antiseptic catheters respectively). Two of our cases in the control group died directly due to catheter-related candidemia. No adverse reactions such as hypersensitivity or leukopenia were found in the antiseptic catheter group. Our study showed that central venous catheters with antiseptic coating were safe and had less risk of colonization of bacteria and fungi than standard catheters in the critically ill patients.",
"Central venous catheterization is one of the important sepsis reasons in surgical patients. In this randomized controlled study, the effect of the frequency and type of catheter site care, as well as age, coexisting malignancy or diabetes mellitus, total parenteral nutrition administration and antibiotics use, on central venous catheter infection was investigated. Seventy-two single-lumen polyurethane catheters were included. In group I (n: 33), a transparent occlusive dressing was applied to the insertion site and not removed for 7 days unless there were signs of local infection. In group II (n: 39), daily site care was done with povidone-iodine 10% solution and a new sterile gauze was applied. Chi-square, linear correlation and multiple regression tests were used for statistical analysis. Mean duration of catheters was 8 +/- 4 days. There was no catheter-related sepsis. Ten (13.9%) patients had positive catheter tip cultures of whom three had site infection as well. The incidence of site and tip infections were not significantly different in group I and II (p > 0.05). Site infection and age younger than 60 years significantly increased the rate of tip infection (p: 0.004 and p: 0.02 respectively). Total parenteral nutrition administration was associated with higher rate of tip infection (p: 0.06). Coexisting malignancy or diabetes mellitus, duration of catheter and antibiotics use did not have any significant effect on the rate of central venous catheter infections (p > 0.05). In conclusion, we observed that the frequency of insertion site care and the type of dressing applied to the site had no significant effect on the rate of CVC infection. Insertion site infection was the most significant factor increasing the incidence of catheter tip infection. The use of the CVC for total parenteral nutrition facilitated tip infection as well.",
"To test the efficacy of the ARROWgard (Arrow International Inc, Reading, Pa) central venous catheter (CVC) coated with silver sulfadiazine and chlorhexidine (A-CVC) in the prevention of CVC-related infections.\n Prospective, randomized trial.\n A tertiary care medical center.\n Two hundred eighty-two patients who required CVC placement were evaluated in this study. Patients were prospectively randomized to receive either a standard CVC (S-CVC) or the A-CVC. Only fresh-stick double- and triple-lumen catheters were studied.\n Patients were evaluated for catheter site inflammation, catheter site colonization, local catheter-related infection, and catheter-related septicemia.\n The 2 groups were matched for age, percentage in the intensive care unit, percentage receiving total parenteral nutrition, percentage with triple-lumen catheters, and duration of catheterization. Rates of catheter site inflammation in the 2 groups were similar (12% vs 10%, S-CVC group and A-CVC group, respectively). The A-CVC was associated with a significantly decreased catheter site colonization rate (49% vs 28%; 43% reduction; P<.001) and local catheter-related infection rate (22.4% vs 5.8%; 74% reduction; P<.001). Rates of catheter-related septicemia were reduced by 41% in the A-CVC group (6.4% vs 3.8%, S-CVC group and A-CVC group, respectively), but this was not statistically significant.\n Despite a marked decrease in catheter site colonization and catheter-related infection rates, the A-CVC did not significantly reduce the incidence of catheter-related septicemia. This may be due to a greater pathogenic dependence on catheter hub contamination rather than catheter site colonization or local catheter-related infection, or the relatively short (5.2 days) duration of catheterization in this study.",
"Central venous catheter-related infections are a significant medical problem. Improved preventive measures are needed.\n To ascertain 1) effectiveness of a second-generation antiseptic-coated catheter in the prevention of microbial colonization and infection; 2) safety and tolerability of this device; 3) microbiology of infected catheters; and 4) propensity for the development of antiseptic resistance.\n Multicenter, randomized, double-blind, controlled trial.\n 9 university-affiliated medical centers.\n 780 patients in intensive care units who required central venous catheterization.\n Patients received either a standard catheter or a catheter coated with chlorhexidine and silver sulfadiazine.\n The authors assessed catheter colonization and catheter-related infection, characterized microbes by molecular typing, and determined their susceptibility to antiseptics. Patient tolerance of the catheter was monitored.\n Patients with the 2 types of catheters had similar demographic features, clinical interventions, laboratory values, and risk factors for infection. Antiseptic catheters were less likely to be colonized at the time of removal compared with control catheters (13.3 vs. 24.1 colonized catheters per 1000 catheter-days; P < 0.01). The center-stratified Cox regression hazard ratio for colonization controlling for sampling design and potentially confounding variables was 0.45 (95% CI, 0.25 to 0.78). The rate of definitive catheter-related bloodstream infection was 1.24 per 1000 catheter-days (CI, 0.26 to 3.62 per 1000 catheter-days) for the control group versus 0.42 per 1000 catheter-days (CI, 0.01 to 2.34 per 1000 catheter-days) for the antiseptic catheter group (P = 0.6). Coagulase-negative staphylococci and other gram-positive organisms were the most frequent microbes to colonize catheters. Noninfectious adverse events were similar in both groups. Antiseptic susceptibility was similar for microbes recovered from either group.\n The antiseptic catheter was not compared with an antibiotic-coated catheter, and no conclusion can be made regarding its effect on bloodstream infection.\n The second-generation chlorhexidine-silver sulfadiazine catheter is well tolerated. Antiseptic coating appears to reduce microbial colonization of the catheter compared with an uncoated catheter."
] |
We found a four-fold increase in the rate of catheter related blood stream infection when a polyurethane dressing was used to secure the central venous catheter however this research was at risk of bias and the confidence intervals were wide indicating high uncertainty around this estimate; so the true effect could be as small as 2% or as high as 17-fold. More, better quality research is needed regarding the relative effects of gauze and tape versus polyurethane dressings for central venous catheter sites.
|
CD001239
|
[
"10745332",
"10074720",
"10832472",
"7996367",
"8260542",
"1517923"
] |
[
"Multicenter randomized placebo controlled trial of therapy with intravenous immunoglobulin in decreasing mortality due to neonatal sepsis.",
"The use of prophylactic intravenous immunoglobulin therapy in very low birthweight infants.",
"Intravenous immunoglobulin for prophylaxis of nosocomial sepsis.",
"Intravenous immune globulin prophylaxis of late-onset sepsis in premature neonates.",
"The use of intravenously administered immunoglobulins in the prevention of severe infection in very low birth weight neonates.",
"Intravenous immune globulin therapy for early-onset sepsis in premature neonates."
] |
[
"To determine whether therapy with intravenous immunoglobulin G (IVIG) would decrease mortality in neonatal sepsis.\n Three tertiary care neonatal intensive care units in the city of Bangalore.\n All neonates admitted to the Neonatal Intensive Care Units with the clinical diagnosis of sepsis and having at least C-reactive protein and one other rapid diagnostic criteria positive were enrolled. Neonates with a birth weight of less than 1000 g and those with any major congenital malformation were excluded. The neonates were randomized to receive 1 g/kg of IVIG on three consecutive days or an equivalent amount of placebo. The rest of the treatment including antibiotics and supportive care was as per the treating physician's decision. The main outcome variable was survival.\n The trial was carried out over a period of 8 months and recruited 58 neonates. Seven neonates who qualified but did not receive either IVIG or placebo were taken into a separate control group, and one baby who received only one dose of IVIG was excluded from the analysis. Twenty-five neonates were enrolled into the IVIG arm and 25 in the placebo arm. The neonates in the therapy and placebo groups were comparable in terms of birth weight (2144+/-675 g vs. 2072+/-682 g), gestation (37.0+/-3.56 vs. 35.8+/-3.52 weeks), sex distribution, duration of stay, and number requiring ventilation. The placebo group had a significantly higher number of babies with positive blood culture. Seven babies in each group died (p>0.05). There was no significant benefit in using IVIG (OR 1.0; 95% CI 0.25-4.07) (p = 0.74).\n In the sample studied therapy with IVIG did not reduce mortality in neonatal sepsis",
"Nosocomial infections are a major cause of death in premature infants, especially in very low birthweight (VLBW) infants. The VLBW infants have low serum immunoglobulin G levels, which may have an effect on infections in early infancy. Thus, prophylactic administration of intravenous immunoglobulin (IVIG) is proposed to maintain higher immunoglobulin G and reduce the rate of hospital-acquired infection.\n A study for the effects of prophylactic IVIG therapy in VLBW infants was performed. A total of 61 VLBW infants were enrolled, and divided into the IVIG group (n = 31) and the control group (n = 30). The dose for each infant was 750-1000 mg/kg for those whose birthweight was less than 1000 g, and 500-750 mg/kg for infants whose birthweight was between 1001 and 1500 g. The control group received saline infusion. The infusions were given every 2 weeks until the infant weighed 1800 g, or was discharged.\n The results showed: there were no major differences in the perinatal and neonatal characteristics between the two groups, consistently higher IgG levels were found in the IVIG group, and the age of first documented sepsis was earlier in the control group.\n In this study, the prophylactic IVIG therapy may give substantially higher IgG levels, which may last for 2 months. However, a prophylactic effect for hospital-acquired infections was not observed.",
"A total of 76 premature newborn infants with gestational age of 34 weeks or less were enrolled in a randomized controlled study to determine whether intravenously administrated immunoglobulin (IVIG) is able to prevent nosocomial sepsis. Forty infants were given 0.5 g/kg IVIG on the first day of life and 36 infants with similar gestational age and birth weight were selected as controls and did not receive IVIG. The frequency of proven sepsis, with a positive blood and/or cerebrospinal fluid culture, was significantly lower in infants who received IVIG as compared to controls (42.5 vs 80.0%) (p < 0.01). The mortality rate attributable to infection was not different in IVIG recipients and in controls (41 vs 48%) (p > 0.05). The overall mortality rates in the two groups were not different either (35.0 vs 44.4%) (p > 0.05). The majority of micro-organisms isolated from the blood culture of the patients were gram negative microorganisms (Klebsiella, Enterobacter). IVIG therapy was believed to be effective for prophylaxis of nosocomial infection, but such therapy was not able to reduce overall mortality rate or mortality rate due to systemic infection in prematurely born infants in our intensive care unit where the causative pathogens are usually gram negative microorganisms.",
"To determine whether a single dose of intravenously administered immune globulin (IVIG) decreases late-onset sepsis in premature infants, we prospectively entered 753 neonates with birth weight 500 to 2000 gm, gestation < or = 34 weeks, and age < or = 12 hours into a multicenter, double-blind, controlled trial. Infants were randomly selected to receive a single intravenous infusion, 10 ml/kg, of either IVIG (500 mg/kg) or albumin (5 mg/kg) and were observed for 8 weeks for infection. Maternal and neonatal risk factors for infection did not differ between groups. Although serum IgG values before infusion were related to gestation (R = 0.62), the change in serum IgG or half-life of IgG after IVIG infusion was not (R < or = 0.09). The serum IgG concentration was increased (p < 0.05) in IVIG-treated patients for 8 weeks. There were 88 episodes of late-onset sepsis in 79 neonates (10.5%). Causative organisms included the following: Staphylococcus epidermidis (37 episodes), Enterococcus (9), Staphylococcus aureus (7), Candida (6), Escherichia coli (6), and multiple organisms (11). Sepsis, death, and death as a result of infection were unaffected by treatment. We conclude that a single infusion of IVIG, 500 mg/kg, shortly after birth was not effective prophylaxis for late-onset infection in premature neonates. Future studies of late-onset sepsis prophylaxis should consider IVIG with known pathogen-specific antibody concentrations against organisms causing these infections, in particular S. epidermidis.",
"In a randomized prospective study in 116 selected neonates with very low birth weight, the effect of standard doses of intravenously administered immunoglobulins (IVIG) on the occurrence of severe infections was studied. No difference in infection rate or severity of infection could be observed between the treated neonates and the control group. The lack of effect could not be explained by an insufficient increase in the IgG serum levels, or inversely, by high immunosuppressive IgG levels. It is concluded that in very low birth weight neonates the administration of IVIG, under the conditions used in this investigation, does not protect against severe infection.",
"Newborn infants may have IgG deficiencies that increase their susceptibility to bacterial infection. To determine whether intravenous immune globulin (IVIG) therapy improves survival rates in early-onset sepsis, we prospectively entered 753 neonates (birth weight 500 to 2000 gm, gestation less than or equal to 34 weeks, age less than or equal to 12 hours) into a multicenter, double-blind, controlled trial. Blood culture specimens were obtained and infants randomly assigned to receive 10 ml (per kilogram) intravenously of a selected IVIG (500 mg/kg) or albumin (5 mg/kg) preparation. Maternal and neonatal risk factors were not different between groups. Thirty-one babies (4.2%) had early-onset sepsis; the causative organisms were group B streptococcus (12 babies), Escherichia coli (6), and others (13). Of these 31 neonates, 7 (23%) died. Total serum IgG was higher for 7 days after IVIG therapy than after albumin treatment (p less than 0.05). During these 7 days, 5 (30%) of 17 albumin-treated and none of 14 IVIG-treated patients died (p less than 0.05). The survival rate at 56 days of age, however, was not significantly improved. Group B streptococcus type-specific IgG antibody was significantly increased after IVIG treatment and appeared to be related to the amount of IVIG specific antibody. Infusion-related adverse reactions were less frequent in patients receiving IVIG therapy (0.5%) than in those receiving albumin. The IVIG therapy in neonates with early-onset sepsis, while reducing the early mortality rate, did not significantly affect the overall survival rate. Further studies are necessary to confirm these findings and to determine more effective therapeutic regimens."
] |
In previous reviews, we encouraged researchers to undertake well-designed trials to confirm or refute the effectiveness of IVIG in reducing adverse outcomes in neonates with suspected infection. Such a trial has been undertaken. Results of the INIS trial, which enrolled 3493 infants, carry a heavy weight in the current update of this review, and the undisputed results show no reduction in death or major disability at 2 years of age. Routine administration of IVIG to prevent mortality in infants with suspected or proven neonatal infection is not recommended.
|
CD000941
|
[
"15777441",
"16001749",
"15951101",
"11641677",
"15104606",
"8694043",
"11561740",
"17722318",
"12554247",
"11759980",
"10338065",
"15327448",
"11212999",
"12648175",
"9322632",
"7675376",
"11430966",
"10453828",
"17629164",
"17077234",
"11075969",
"12830602",
"9290452",
"7778636",
"11006200",
"9704771",
"14616254",
"15746667",
"14526301",
"9396885",
"18165400",
"12118642",
"8841210",
"14993717",
"15884282",
"11803223",
"7778637",
"11787914",
"12767565",
"15229013",
"15036709",
"17028904",
"18399337",
"16455695",
"9170463",
"12512928",
"15603033",
"10329871",
"11810088",
"12504970",
"12789117",
"11444788",
"12388963",
"9397101",
"11952465",
"15284771",
"21130990",
"16753768",
"16129547",
"20636243",
"11966483",
"9491868",
"12755528",
"12681871",
"18715414",
"12841697",
"10438440",
"12798539",
"18569471",
"9803069",
"12920470",
"17343543",
"16929421",
"10368502",
"10426647",
"11814498",
"15841929",
"11453262",
"15450119",
"10688506",
"18850516",
"14586349",
"14687051",
"12548212",
"16398773",
"11814497",
"11704083",
"16101611",
"14643034",
"17326881",
"10853403",
"10960643",
"9351755",
"9083316",
"16406221",
"12830603"
] |
[
"A randomised controlled trial comparing low dose vaginal misoprostol and dinoprostone vaginal gel for inducing labour at term.",
"[Comparative study of the effect of intravaginal misoprostol at 50 and 100 micrograms in cervical ripening and labor induction].",
"A comparison of oral and vaginal misoprostol for induction of labor.",
"A comparison of various routes and dosages of misoprostol for cervical ripening and the induction of labor.",
"A randomised comparison of oral misoprostol and vaginal prostaglandin E2 tablets in labour induction at term.",
"A comparison of differing dosing regimens of vaginally administered misoprostol for preinduction cervical ripening and labor induction.",
"Randomized controlled trial of 50 and 100 mcg of misoprostol for induction of labor at term.",
"A comparison between single dose of 50 microg oral misoprostol and 25 microg vaginal misoprostol for labor induction.",
"No benefit, but increased harm from high dose (100 microg) misoprostol for induction of labour: a randomised trial of high vs. low (50 microg) dose misoprostol.",
"A comparison between 50 mcg oral misoprostol every 4 hours and 6 hours for labor induction: a prospective randomized controlled trial.",
"A double-blind randomized trial of two dose regimens of misoprostol for cervical ripening and labor induction.",
"Comparison of oral and vaginal misoprostol for induction of labor at term: a randomized controlled trial.",
"A comparison of oral and vaginal misoprostol for induction of labour at term: a randomised trial.",
"Randomized trial in multiparous patients: investigating a single vs. two-dose regimen of intravaginal misoprostol for induction of labor.",
"A comparison of intermittent vaginal administration of misoprostol with continuous dinoprostone for cervical ripening and labor induction.",
"Randomized controlled trial of vaginal misoprostol and intracervical prostaglandin E2 gel for induction of labor at term.",
"Safety and efficacy of misoprostol orally and vaginally: a randomized trial.",
"Misoprostol for induction of labour at term: a more effective agent than dinoprostone vaginal gel.",
"Labor induction at term: a comparison of the effects of 50 microg and 25 microg vaginal misoprostol.",
"Controlled-release misoprostol vaginal insert in parous women for labor induction: a randomized controlled trial.",
"A randomized comparison of one single dose of vaginal 50 microg misoprostol with 3 mg dinoprostone in pre-induction cervical ripening.",
"Misoprostol for cervical ripening at and near term--a comparative study.",
"Randomized trial of two doses of the prostaglandin E1 analog misoprostol for labor induction.",
"A comparison of misoprostol and prostaglandin E2 gel for preinduction cervical ripening and labor induction.",
"Randomized comparison of vaginal (200 microg every 3 h) and oral (400 microg every 3 h) misoprostol when combined with mifepristone in termination of second trimester pregnancy.",
"Induction of labor with misoprostol for premature rupture of membranes beyond thirty-six weeks' gestation.",
"Oral misoprostol (100 microg) versus vaginal misoprostol (25 microg) in term labor induction: a randomized comparison.",
"Prospective randomized clinical trial of inpatient cervical ripening with stepwise oral misoprostol vs vaginal misoprostol.",
"Oral misoprostol for premature rupture of membranes at term.",
"A double-blind comparison of the safety and efficacy of intravaginal misoprostol and prostaglandin E2 to induce labor.",
"Titrated oral compared with vaginal misoprostol for labor induction: a randomized controlled trial.",
"Sublingual compared with oral misoprostol in term labour induction: a randomised controlled trial.",
"Vaginal misoprostol for induction of labor: a randomized controlled trial.",
"Sublingual misoprostol before first trimester abortion: a comparative study using two dose regimens.",
"Comparison of vaginal and oral misoprostol, for the induction of labour in women with intra-uterine foetal death.",
"Comparison of 25 and 50 microg vaginally administered misoprostol for preinduction of cervical ripening and labor induction.",
"Misoprostol: an effective agent for cervical ripening and labor induction.",
"A randomised trial of oral versus vaginal administration of misoprostol for the purpose of mid-trimester termination of pregnancy.",
"Labor induction post-term with 25 micrograms vs. 50 micrograms of intravaginal misoprostol.",
"Vaginal misoprostol versus concentrated oxytocin and vaginal PGE2 for second-trimester labor induction.",
"Induction of labor with 50 and 100 microg of misoprostol: comparison of maternal and fetal outcomes.",
"A randomized comparison between intravaginal misoprostol and prostaglandin E2 for labor induction.",
"Efficacy and safety of misoprostol in induction of labour in a Nigerian tertiary hospital.",
"Oral misoprostol for induction of labour at term: randomised controlled trial.",
"Labor induction with intravaginal misoprostol in term premature rupture of membranes: a randomized study.",
"A comparison of 100 microg oral misoprostol every 3 hours and 6 hours for labor induction: a randomized controlled trial.",
"Vaginal misoprostol in managing premature rupture of membranes.",
"A comparison of orally administered misoprostol with vaginally administered misoprostol for cervical ripening and labor induction.",
"Sublingual misoprostol for the induction of labor at term.",
"Active management of term prelabour rupture of membranes with oral misoprostol.",
"A comparative study of vaginal misoprostol and intravenous oxytocin for induction of labour in women with intra uterine fetal death in Mulago Hospital, Uganda.",
"A comparison of intermittent vaginal administration of two different doses of misoprostol suppositories with continuous dinoprostone for cervical ripening and labor induction.",
"A randomized controlled trial comparing two protocols for the use of misoprostol in midtrimester pregnancy termination.",
"Extemporaneous preparation of misoprostol gel for cervical ripening: a randomized trial.",
"A comparison of two dosage regimens of oral misoprostol for labor induction at term.",
"A comparison of orally administered misoprostol to intravenous oxytocin for labor induction in women with favorable cervical examinations.",
"Administration of 400 μg of misoprostol to augment routine active management of the third stage of labor.",
"A prospective randomized study comparing misoprostol and oxytocin for premature rupture of membranes at term.",
"Induction of labor in great grandmultipara with misoprostol.",
"A randomized controlled trial comparing vaginal misoprostol versus Foley catheter plus oxytocin for labor induction.",
"Induction of labor in toxemia with misoprostol.",
"Labor induction with prostaglandin E1 misoprostol compared with dinoprostone vaginal insert: a randomized trial.",
"A comparison between intravaginal and oral misoprostol for labor induction: a randomized controlled trial.",
"Ruptured membranes at term: randomized, double-blind trial of oral misoprostol for labor induction.",
"Induction of labour in nulliparous and multiparous women: a UK, multicentre, open-label study of intravaginal misoprostol in comparison with dinoprostone.",
"Six hourly vaginal misoprostol versus intracervical dinoprostone for cervical ripening and labor induction.",
"The use of misoprostol for pre-operative cervical dilatation prior to vacuum aspiration: a randomized trial.",
"A comparison of oral misoprostol with vaginal misoprostol administration in second-trimester pregnancy termination for fetal abnormality.",
"Prospective randomised controlled trial to compare safety and efficacy of intravaginal Misoprostol with intracervical Cerviprime for induction of labour with unfavourable cervix.",
"A comparison between 25 micrograms and 50 micrograms of intravaginal misoprostol for labor induction.",
"Misoprostol versus oxytocin for labor induction in term and post-term pregnancy: randomized controlled trial.",
"Induction of labor with oral misoprostol for premature rupture of membranes at term in women with unfavorable cervix: a randomized, double-blind, placebo-controlled trial.",
"Oral misoprostol for induction of labor in prelabor rupture of membranes (PROM) at term: a randomized control trial.",
"Misoprostol is more efficacious for labor induction than prostaglandin E2, but is it associated with more risk?",
"Vaginal misoprostol for pre-abortion cervical priming: is there an optimal evacuation time interval?",
"Prostaglandin E2 gel versus misoprostol for cervical ripening in patients with premature rupture of membranes after 34 weeks.",
"Randomized comparison of 3 misoprostol protocols for abortion induction at 13-20 weeks of gestation.",
"Misoprostol versus dinoprostone for cervical priming prior to induction of labour in term pregnancy: a randomised controlled trial.",
"Comparison of misoprostol and dinoprostone for elective induction of labour in nulliparous women at full term: a randomized prospective study.",
"Labour characteristics and uterine activity: misoprostol compared with oxytocin in women at term with prelabour rupture of the membranes.",
"A randomized clinical trial comparing vaginal misoprostol versus cervical Foley plus oral misoprostol for cervical ripening and labor induction.",
"The MisoPROM study: a multicenter randomized comparison of oral misoprostol and oxytocin for premature rupture of membranes at term.",
"A randomised trial comparing low dose vaginal misoprostol and dinoprostone for labour induction.",
"Oral misoprostol or vaginal dinoprostone for labor induction: a randomized controlled trial.",
"Oral versus self-administered vaginal misoprostol at home before surgical termination of pregnancy: a randomised controlled trial.",
"Oral and vaginal misoprostol compared with dinoprostone for induction of labor: a randomized controlled trial.",
"Randomized trial of oral versus vaginal misoprostol at one day after mifepristone for early medical abortion.",
"A randomised controlled trial of 6 and 12 hourly administration of vaginal misoprostol for second trimester pregnancy termination.",
"Cervical ripening with oral misoprostol at term.",
"Induction of labour with intravaginal misoprostol and prostaglandin E2 gel: a comparative study.",
"Randomised controlled trial of the efficacy of misoprostol used as a cervical ripening agent prior to termination of pregnancy in the first trimester.",
"Oral misoprostol and intracervical dinoprostone for cervical ripening and labor induction: a randomized comparison.",
"Vaginal misoprostol compared with oral misoprostol in termination of second-trimester pregnancy.",
"A randomized comparison between misoprostol and dinoprostone for cervical ripening and labor induction in patients with unfavorable cervices.",
"Induction of labor with misoprostol in pregnancies with advanced maternal age.",
"Labour induction at term--a randomised trial comparing Foley catheter plus titrated oral misoprostol solution, titrated oral misoprostol solution alone, and dinoprostone."
] |
[
"To compare the efficacy of low dose vaginal misoprostol and dinoprostone vaginal gel for induction of labour at term.\n A single-blind randomised controlled trial.\n Antenatal and labour ward of a UK district general hospital.\n Two hundred and sixty-eight women requiring induction of labour at term (>37 weeks of gestation) with no significant fetal or medical condition, no previous uterine surgery and no contraindication to prostaglandin.\n Misoprostol 25 microg (one-quarter of a 100 microg tablet) was inserted into the posterior vaginal fornix every 4 hours (to a maximum of six doses) or dinoprostone vaginal gel 1-2 mg 6 hourly (maximum of 3 mg in 24 hours).\n Induction-to-vaginal delivery interval.\n Requirements for oxytocin, mode of delivery, number of women delivering < 24 hours, incidence of uterine contraction abnormalities, incidence of abnormal cardiotocograph (CTG) recordings, 5-minute Apgar scores, umbilical cord pH recordings, analgesia requirements, admission to NICU and blood loss at delivery.\n There were no significant differences between the two groups in induction-to-vaginal delivery interval, mode of delivery, number of women delivering within 24 hours and neonatal outcomes. The incidence of uterine contraction abnormalities (tachysystole and hyperstimulation) and the incidence of abnormal CTG recordings were also similar for both groups.\n Low dose vaginal misoprostol is as effective as dinoprostone gel for inducing labour at term. There would be substantial cost savings, estimated at around 3.9 million UK pounds per annum, for maternity services if low dose misoprostol became the agent of choice for inducing labour in the UK.",
"The objective of this work was to compare the efficacy of 50 and 100 microg of misoprostol administered intravaginally for cervical ripening and labor induction. Ninety-five patients were randomly assigned to receive 50 microg (n=48) or 100 microg (n=47) of misoprostol. The primary measures in this study were cesarean section rate, time from induction to delivery, need for oxytocin use, rate of uterine hyperstimulation and tachysystoles, proportion of fetal distress and neonatal Apgar score. The interval from first dose of prostaglandin to delivery was significantly shorter in the 100 ,g-group (p < 0.05). The use of oxytocin augmentation was significantly higher in the 50 microg-group (64.6% vs. 31.9%). There were 9 cases (18.8%) of tachysystole in the 50-microg group and 12 cases (25.5%) in the 100 microg-group (p NS). The cesarean section rate was double in the 100 microg-group and the difference was statically significant (p < 0.05). There was no report of uterine rupture. It can be concluded that 50 microg of misoprostol applied in the posterior vaginal fornix every 4 hours is an effective dosage for labor induction and has less adverse effects and complications than the 100 microg dose.",
"The aim of the study is to compare the efficacy and safety of oral (100 microg) and vaginal (50 microg) misoprostol for labor induction.\n Ninety-nine patients with indications for labor induction randomly received 100 microg oral misoprostol every 4 h or 50 microg vaginal misoprostol every 4 h, using maximum six doses. Mean induction to delivery interval, mode of delivery, rates of tachysystole, hypertonus and hyperstimulation syndrome, oxytocin use, number of doses used, failed induction rate and neonatal outcomes were compared for the two groups.\n Mean dose of misoprostol used for oral and vaginal misoprostol groups were 2.17+/-1.35 and 1.91+/-0.94, respectively (p=0.65). There were two failed inductions in the oral (4%) and one failed induction (2.5%) in the vaginal group after a total of six doses of misoprostol (p=0.58). There was no significant difference for the mean induction to delivery interval, to the beginning of active phase interval, active phase duration, second stage duration and the number of women who received oxytocin for induction or augmentation between the two groups (p>0.05). There were also no significant differences for intrapartum complications and neonatal outcomes between the oral and vaginal misoprostol groups (p>0.05).\n Our findings indicate that, in a closely supervised hospital setting with adequate monitoring, 100 microg oral misoprostol has the potential to induce labor as safely and effectively as its 50 microg vaginal analogue. As oral use of the drug is easier for both the patient and the doctor, oral misoprostol will probably be more preferable than the vaginal route.",
"The purpose of this study was to compare the efficacy of different routes of misoprostol administration for cervical ripening and the induction of labor.\n Three hundred thirty women at > or = 32 weeks gestation with a Bishop score < or = 6 and an indication for induction were randomized to 1 of 3 double-blinded groups: (1) 25 microg orally administered misoprostol plus 25 microg vaginally administered misoprostol, (2) orally administered placebo plus 25 microg vaginally administered misoprostol, or (3) 25 microg orally administered misoprostol plus vaginally administered placebo. Doses were repeated every 4 hours until onset of labor or a maximum of 12 doses were given. The primary outcome of the trial was vaginal delivery within 24 hours of the initiation of induction. Secondary outcomes were the time from induction to delivery, need for oxytocin augmentation, mode of delivery, frequency of side effects, and neonatal and maternal outcome. Analysis of variance, chi-square test, and logistic regression were used for analysis.\n There were no significant differences in maternal characteristics or indications for induction. The percentage of women who achieved vaginal delivery within 24 hours was highest in the vaginally administered misoprostol group: 67% compared with 53% in the oral-plus-vaginal group (P < .05) and 36% in the oral group (P < .05). The median time to vaginal delivery was shorter in the vaginal and oral-plus-vaginal misoprostol groups, 13.5 hours and 14.3 hours, respectively, when compared with 23.9 hours in the oral group (P < .05). The rate of cesarean delivery was lowest in the vaginal misoprostol group (17% compared with 30% in the oral-plus-vaginal group and 32% in the oral group; P < .05). Uterine tachysystole occurred least frequently in the oral misoprostol group (10% compared with 32% in the vaginal group and 34% in the oral-plus-vaginal group; P < .05). Uterine hyperstimulation also occurred least frequently in the oral misopro-stol group (4% compared with 15% in the vaginal group and 22% in the oral-plus-vaginal group; P < .05).\n At the doses studied, induction of labor with vaginally administered misoprostol is more efficacious than either oral-plus-vaginal or oral-only route of administration.",
"To compare the efficacy of 100 microg of oral misoprostol with 3 mg prostaglandin E2 vaginal tablets in term labour induction.\n A non-blinded, randomised, controlled trial.\n A tertiary level, teaching Scottish Hospital.\n Two hundred women at term with indications for labour induction and modified Bishop's cervical score of less than 8.\n The women were randomly allocated to receive either 100 microg of misoprostol orally (which could be repeated 4 hourly to a maximum of five doses if indicated), or a 3 mg tablet of prostaglandin E2 vaginally (which could be repeated in 6 hours, according to routine departmental protocol).\n The number delivering vaginally within 24 hours of the induction.\n Seventy-five women delivered vaginally in the misoprostol group and 73 in the PGE2 group. Of these, 50.7% in the misoprostol group and 54.8% in the PGE2 group delivered within 24 hours of the induction (RR 0.92, 95% CI 0.7 to 1.3). More women in the misoprostol group were given oxytocin, but this was not statistically significant (60%vs 47%, RR 1.3, 95% CI 0.98 to 1.7). Two women in the misoprostol group had uterine hyperstimulation. The neonatal outcomes were not significantly different in the two groups. There was a pound 1100 saving on direct drug costs in the misoprostol group.\n Oral misoprostol (100 microg) has similar efficacy to vaginal PGE2 tablets, and may be an option to consider for term labour induction.",
"Our purpose was to compare two dosing regimens of vaginally administered misoprostol for preinduction cervical ripening and induction of labor.\n Five hundred twenty-two patients with indications for induction of labor and unfavorable cervices were randomly assigned to one of two dosing regimens of vaginally administered misoprostol. Twenty-five microgram tablets of misoprostol were placed in the posterior vaginal fornix either every 3 hours to a maximum of eight doses or every 6 hours to a maximum of four doses. The maximal period of cervical ripening was 24 hours regardless of the number of misoprostol doses administered. Medication was not given after either spontaneous rupture of membranes or the beginning of active labor.\n Among 522 patients enrolled, 261 were randomized to receive misoprostol every 3 hours and 261 to receive misoprostol every 6 hours. The average interval from start of induction to vaginal delivery was shorter in the 3-hour dosing group (1311.74 +/- 785.14 minutes) than in the 6-hour dosing group (1476.96 +/- 805.30 minutes) (p < 0.05). Oxytocin augmentation of labor occurred more commonly in the 6-hour dosing group (51.4%) than in the 3-hour dosing group (41.8%) (p < 0.05) [corrected]. There were no significant differences between routes of delivery. Overall, 108 patients (20.8%) were delivered by cesarean section. There was a slightly higher prevalence of tachysystole (six or more uterine contractions in a 10-minute window for two consecutive 10-minute periods) in the 3-hour group (14.6%) than in the 6-hour group (11.2%), but this difference was not statistically different. There were no significant differences in the frequency of uterine hyperstimulation or hypertonus. There was no significant difference between groups in the frequency of abnormal fetal heart rate tracings, meconium passage, 1- or 5-minute Apgar scores < 7, neonatal resuscitations, or admissions to the neonatal intensive care unit.\n Vaginally administered misoprostol is an effective agent for cervical ripening and induction of labor. Patients with the 6-hour dosing schedule had longer intervals to delivery, more frequently required oxytocin augmentation, and had more failed inductions than did patients with 3-hour dosing. Further investigation to characterize the safety of misoprostol is needed.",
"To compare the safety and efficacy of two different regimens of misoprostol for labor induction at term, we conducted a randomized controlled trial on women presenting for induction of labor at > or =37 weeks' gestation. Eligible women were randomized to receive intravaginal misoprostol 50 microg every 4 h or 100 microg every 6 h until any of the following: 1) adequate contraction pattern (3 contractions/10 min); 2) dilatation >3 cm; 3) artificial rupture of membranes; or 4) signs of uterine hyperstimulation. Use of oxytocin during labor was at the discretion of the managing clinician. The main outcome variable considered for analysis was cesarean section rate. Secondary outcome measures were induction to delivery interval and neonatal outcome (Apgar scores, meconium staining, and umbilical artery pH). A total of 58 women were randomized to receive either misoprostol 100 microg (n=26) or 50 microg (n=32). The 100 and 50 microg groups had similar mean Bishop's scores at induction (4.0+/-2.3 vs 4.1+/-2.2, p=0.87), rates of nulliparity, use of epidural anesthesia, and oxytocin augmentation. The number of doses of misoprostol used was similar in the two groups (1.4+/-0.6 vs 1.8+/-1.2). The mean+/-standard deviation time to delivery (hours) (11.9+/-7.3 vs 14.3+/-9.6 h, p=0.30) and cesarean section rate (35% vs 19%, p=0.30, relative risk: 1.8, 95% confidence interval 0.7-5.4) were not different in the 100 vs 50 microg group. Power analysis demonstrated that 132 women would be required in each group to achieve statistical significance in the primary outcome measure (alpha=0.05, beta=0.80). Similarly, rates of 5-minute Apgar scores <7 (4% vs 3%, p=1.0), and of meconium passage (17% vs 25%, p=0.73) were not significantly different between the two groups.",
"To compare the efficacy and safety of a single dose of 50 microg oral misoprostol with 25 microg vaginal misoprostol for labor induction.\n This study was a randomized, double-blind controlled trial conducting in pregnant women admitted at delivery room, Department of Obstetrics and Gynecology, Bangkok Metropolitan Administration Medical College and Vajira Hospital between March 2002 and January 2005. All 146 pregnancies at > or = 37 weeks' gestation who had indication for labor induction with unfavorable cervix were randomly divided into a group of single dose of 50 microg misoprostol orally or 25 microg misoprostol vaginally. Initial and six hours after misoprostol administration, Bishop scores were evaluated. Requirement of oxytocin augmentation, complication due to uterine hypertonus, incidence of vaginal delivery, Apgar score at 1 and 5 minutes, and number of neonate admitted at neonatal intensive care unit (NICU) were recorded.\n The baseline characteristics and median initial Bishop scores were comparable in both groups. At 6 hours after misoprostol administration the median cervical changes of women who received oral or vaginal misoprostol were statistically significant different, 3 and 4, respectively. The median time interval to vaginal delivery of women who received oral misoprostol was significantly longer than of those who had vaginal drug, 16.9 and 11.8 hours respectively. Comparable neonatal outcomes were found in both groups in terms of assigned Apgar score at 1 and 5 minutes.\n A single dose of 25 microg vaginal misoprostol appears to be more effective than 50 microg oral dose in improving Bishop scores and decreasing the time to vaginal delivery in women with unfavorable cervix without severe adverse effects.",
"Misoprostrol, a synthetic analogue of prostaglandin E(1), has been used for cervical preparation. Its ideal dose, route and frequency of administration are still under investigation. We conducted a randomised controlled trial, in a tertiary hospital in a developing country, to compare misoprostol 50 microg (low) and 100 microg (high) for effectiveness and safety in induction of labour at term. Women admitted for induction of labour with a singleton live fetus in cephalic presentation after 37 weeks' gestation were recruited. A misoprostol tablet was inserted in the posterior vaginal fornix at 8-hour intervals. Main outcomes were duration of induction, maternal and fetal complications. The mean duration of induction was 15.4 (SD 10.6) and 14.2 (SD 13.6) h in the low- and high-groups respectively (P = 0.095). There was no difference in need for augmentation with oxytocin (OR 0.82; 95% Cl 0.36-1.86) or operative delivery (OR 1.29; 95% CI 0.26-6.84). There were two uterine ruptures and four intrapartum stillbirths in the high misoprostol group. There was no difference in postpartum haemorrhage, 9.5% vs. 7.9% (P = 1.00) and admissions to the neonatal unit 18.8% vs. 17.0% (P = 0.980) in the 1ow- and high-groups) respectively. Misoprostol 50 microg was as effective as the 100 microg dose for induction of labour whereas the higher dose had an increased risk of serious complications.",
"To compare the effectiveness and safety between 50 mcg oral misoprostol every 4 hours and 6 hours for labor induction.\n A prospective randomized controlled trial.\n Department of Obstetrics & Gynecology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.\n Eighty nine pregnant women of at least 34 weeks' gestation with indications for labor induction in the condition of unfavourable cervix (Bishop score < or = 4) and no contraindication to prostaglandin therapy.\n All pregnant women were randomized to receive either 50 mcg misoprostol orally every 4 hours or 6 hours.\n Treatment interval from induction to vaginal delivery, maternal and neonatal complication.\n The mean treatment intervals from induction to vaginal delivery were 22.10 +/- 18.49 hours and 20.91 +/- 11.98 hours in the misoprostol group every 4 hours and 6 hours, respectively. The treatment intervals between the two groups were not statistically significant. There was also no significant difference between both groups with regard to maternal and neonatal complications.\n The effectiveness in terms of treatment interval from induction to vaginal delivery were comparable between the two groups, but administration of misoprostol every 6 hours was found to have a slightly shorter interval, although it did not reach statistical significance. No serious maternal and neonatal complication was demonstrated in both groups. Either regimen in this study can be an alternative for labor induction.",
"The objective of this study was to compare the efficacy and safety of two dosing regimens of misoprostol for cervical ripening and labor induction.\n Patients who fulfilled the study criteria were randomized to received misoprostol 25 microg or 50 microg intravaginally every 3 h for a total of eight doses for cervical ripening or until labor was established. Endpoints for successful cervical ripening was achievement of Bishop score of nine or greater, and for labor induction reaching the active phase of labor in the first 24 h. The rates of success, duration of first and second stages of labor, type of delivery, significant side effects, and neonatal outcome were measured and compared between the two study groups. Two hundred and fifty-one patients were randomized in two groups--126 received 50 microg and 125 received 25 microg misoprostol. Demographics of the two study groups were similar.\n Patients in the 50 microg group had a shorter first stage (848 min vs. 1,122 min, P < 0.007), shorter induction-to-vaginal delivery interval (933 min vs. 1,194 min, P < 0.013), decreased incidence of oxytocin augmentation (53.9% vs. 68%, P < 0.015), and decreased total units of oxytocin (2,763 mU vs. 5,236 mU, P < 0.023), but there was a higher hyperstimulation rate (19% vs. 7.2%, P < 0.005).\n Successful induction rate, delivery types, and fetal outcome were similar in both groups. Although the rate of vaginal delivery and neonatal outcome were similar in both groups, the 50 microg regimen had shorter first and second stages of labor, and a higher hyperstimulation rate that was easily manageable, allowing for flexibility in using the higher dose in low-risk pregnancies.",
"To compare the efficacy of oral with vaginal misoprostol for induction of labor at term.\n One hundred and fifty-three pregnant women at term with indications for induction of labor and Bishop score < or = 6 were randomly assigned to receive misoprostol either 100 microg orally or 50 microg vaginally every 6 h for 48 h. Repeated doses were given until Bishop score > or = 8 was achieved or spontaneous rupture of membranes occurred. Those who were not in labor after 48 h had labor induced with amniotomy and oxytocin. The main outcome measure was induction to delivery time.\n The median induction to vaginal delivery time in the oral group (14.3 h) was not significantly different from that of the vaginal group (15.8 h). The median number of doses was also not significantly different in the oral group compared with the vaginal group. There was a significant higher incidence of uterine tachysystole in the vaginal group compared to the oral group (17.1% vs 5.3%, P = 0.032). There was no hyperstimulation in either group. There were no significant differences between the groups with respect to oxytocin augmentation, cesarean section rate, analgesic requirement, and neonatal outcomes.\n Oral administration of 100 microg misoprostol has similar efficacy to intravaginal administration of 50 microg misoprostol for labor induction with less frequent abnormal uterine contractility. 100 microg of misoprostol orally can be used as an alternative to the vaginal route for labor induction.",
"To compare the efficacy of oral with vaginal misoprostol for induction of labour at term.\n Randomised trial.\n Tertiary Care hospital.\n One hundred and sixty-seven women requiring induction of labour.\n The women were randomised to receive 50 microg of misoprostol orally or vaginally every 6 h until the cervix was favourable for amniotomy, spontaneous rupture of membranes, or active labour occurred. Sample size was calculated with a two-tailed alpha of 0.05 and a power of 95% to detect a 5 h difference in induction-to-delivery time. Student's t test was used for comparison of normally distributed continuous variables and the Mann-Whitney U test was used for non-Gaussian distributed continuous variables. Fisher' s exact and chi2 tests were used for comparison of categorical variables. The main outcome measure was induction to delivery time.\n The median induction to delivery time was significantly shorter with vaginal misoprostol (15.7 h range 4.3-55.7), compared with oral misoprostol (23.0 h range 3.2-141.7, P = 0.0013). The median number of doses was also significantly less in the vaginal misoprostol group, 1 (range 1-3), compared with the oral group, 2 (range 1-8), (P < 0.0001). The significant differences in outcome held true when nulliparous and multiparous women were analysed separately. There were no differences between the two routes of administration with respect to rates of hyperstimulation or neonatal asphyxia. There were more caesarean sections in the vaginal misoprostol group, but the difference was not statistically significant.\n Compared with oral misoprostol, vaginal misoprostol for induction of labour at term results in a shorter induction-to-delivery time, with fewer doses required per patient. Vaginal misoprostol may be associated with higher rates of caesarean section than oral misoprostol.",
"Multiparous patients have a higher risk of hyperstimulation and uterine rupture than nulliparous patients. The minimum possible dose of uterotonic drug should be used in induction of labor for multiparous patients to avoid excessive uterine activity, which could increase both maternal and fetal risks.\n One hundred and four women were randomized to either a single dose of 50 micro g of intravaginal misoprostol in 24 h, or two consecutive doses of intravaginal 50 micro g misoprostol 6 h apart.\n The mean induction to delivery interval (789 min [95% CI: 637-941] vs. 576 min [95% CI: 484-667], p = 0.018) and delivery rate within 12 h (63% vs. 83%, p = 0.035) were higher in the two-dose group. The oxytocin augmentation rate (14% vs. 2%, p = 0.03) was higher in the single-dose group. There was a higher rate of clinician input related to suspicious cardiotocographic readings in the single-dose arm (p = 0.04). There was no statistical difference (p > 0.05) between the one- and two-dose regimens with respect to the rates of tachysystole (21% vs. 15%), hyperstimulation (3.9% vs. 0%), and meconium staining at delivery (9.8% vs. 13.2%).\n The two-dose regimen was most efficient, but both regimens were well tolerated by the fetuses.",
"Our purpose was to compare the effect of vaginal administration of misoprostol (Cytotec) with that of dinoprostone (Cervidil) on cervical ripening and labor induction.\n Two hundred patients with indications for induction of labor and unfavorable cervical examinations were randomly assigned to receive vaginally administered misoprostol (prostaglandin E1) or the dinoprostone (prostaglandin E2) vaginal insert. Twenty-five microgram tablets of misoprostol were placed in the posterior vaginal fornix every 4 hours for a maximum of six doses. Additional misoprostol was not given after either spontaneous rupture of membranes, adequate cervical ripening (Bishop score of > or = 8 or cervical dilatation of > or = 3 cm), or beginning of active labor. The vaginal insert, Cervidil, containing 10 mg of dinoprostone in a timed-release preparation was placed in the posterior vaginal formix for a maximum period of 24 hours. The vaginal insert was removed for spontaneous rupture of membranes, entry into active labor, adequate cervical ripening, or abnormality of uterine contractile pattern or fetal cardiac activity.\n Of the 200 patients enrolled, 99 were randomized to misoprostol and 101 to dinoprostone. The average interval from start of induction to vaginal delivery was 1 hour shorter in the misoprostol group (1296.7 +/- 722.1 minutes) than in the dinoprostone group (1360.0 +/- 792.0 minutes), but this difference was not statistically significant (p = 0.97). Oxytocin augmentation of labor was used in 50 (50.5%) misoprostol-treated patients and 43 (43.5%) dinoprostone-treated patients (relative risk 1.14, 95% confidence interval 0.86 to 1.51, p = 0.35). There were no significant differences between routes of delivery with misoprostol or dinoprostone. Overall, 38 patients (19.3%) had cesarean deliveries. There was a significantly lower prevalence of tachysystole (six or more uterine contractions in a 10-minute window for two consecutive 10-minute periods) in the misoprostol group (7.1%) than in the dinoprostone group (18.4%) (relative risk 0.52, 95% confidence interval 0.31 to 0.89, p = 0.02). There were no significant differences in frequency of uterine hyperstimulation or hypertonus. Abnormal fetal heart rate tracings were found in 23 (23.2%) of misoprostol-treated patients and 35 (35.7%) of dinoprostone-treated patients (relative risk 0.73, 95% confidence interval 0.52 to 1.01, p = 0.0546). No significant differences were found in meconium passage, 1- or 5-minute Apgar scores < 7, neonatal resuscitations, or admissions to the neonatal intensive care unit between the two groups.\n Vaginally administered misoprostol is as effective as dinoprostone for cervical ripening and the induction of labor. Mean time intervals to delivery, need for oxytocin augmentation, and routes of delivery were similar between the two groups. Incidence of uterine tachysystole with misoprostol every 4 hours was significantly less than with dinoprostone.",
"To compare misoprostol 25 micrograms administered at 2-hour intervals with intracervical prostaglandin (PG) E2 in women with Bishop scores of 5 or less.\n Subjects were randomly assigned to receive either misoprostol 25 micrograms every 2 hours or a commercially available intracervical preparation containing 0.5 mg of PGE2 gel administered at 6-hour intervals for a maximum of two doses.\n Women who received misoprostol experienced a significantly reduced mean time (+/- standard deviation) from drug administration to onset of three contractions in 10 minutes, 6.7 +/- 5.8 versus 12.4 +/- 9.6 hours (P = .007). Mean time to rupture of membranes was also shorter in the misoprostol group, 9.7 +/- 5.5 versus 13.6 +/- 6.8 hours (P = .01), as was the mean time to delivery, 16.0 +/- 7.7 versus 22.4 +/- 10.9 hours (P = .006). Three patients in the misoprostol group experienced uterine hypertonus but not related fetal morbidity.\n Misoprostol is more effective than intracervical PGE2 in bringing about labor and delivery, but further work is needed to determine the ideal dosing regimen.",
"To compare the safety and efficacy accompanying oral and vaginal misoprostol for cervical ripening.\n One thousand four women with medical or obstetric indications for labor induction and unripe cervices were randomly assigned to receive oral or vaginal misoprostol. Initial doses of 200 microg oral and 50 microg vaginal misoprostol were increased to 300 microg oral and 100 microg vaginal after two doses, to a maximum of six doses. Misoprostol was given every 6 hours in both groups. We anticipated that 11% of women treated vaginally would require intervention during the ripening process. Intervention was defined as interruption of the ripening process before labor or Bishop score of 7 or a lack of response to six misoprostol doses.\n Five hundred three subjects were assigned to oral and 501 to vaginal administration. Oral misoprostol was associated with significantly higher frequencies of intervention (67 [13.3%] versus 42 [8.4%], P =.01), tachysystole (114 [23.6%] versus 85 [17.6%], P =.02), and hyperstimulation (90 [18.6%] versus 66 [13.7%], P =.04). There were no significant differences in cesarean rates (147 [29.2%] versus 120 [24.0%], P =.06), mean number of misoprostol doses used (1.5 versus 1.6, P =.18), or hours from drug administration to delivery (24.5 versus 25.4, P =.77) between the oral and vaginal groups, respectively. The numbers of deliveries between the groups within 24 hours was different (271 [56%] versus 290 [60%], P =.02), oral and vaginal, respectively. No adverse neonatal outcomes were noted.\n Oral misoprostol has similar efficacy as vaginal misoprostol but is associated with a higher frequency of excessive uterine contractility and intervention.",
"To compare the efficacy of vaginal misoprostol and dinoprostone vaginal gel for induction of labour at term.\n A single-blind randomised comparative trial.\n Induction and labour wards of a UK teaching hospital.\n Two hundred and eleven pregnant women at term in whom induction of labour was indicated, and with no contra-indication to the use of prostaglandins for the induction of labour.\n The women were randomly assigned to receive vaginal administration of either misoprostol 50 microg four hourly (to a maximum of four doses) or dinoprostone gel 1 mg six hourly (to a maximum of three doses).\n Time from induction to delivery, oxytocin requirement in labour, analgesic requirement, mode of delivery, neonatal outcome.\n The misoprostol group had a highly significant reduction in median induction-delivery interval compared with the dinoprostone group (14.4 hours vs 22.9 hours; P < 0.00001). In addition, more women delivered after only one dose (77% vs 49%; P < 0.0001, OR 3.51, 95% CI 1.94-6.35), and within 12 and 24 hours. There was a reduced need for oxytocin augmentation in labour (21% vs 47%; P < 0.0001, OR 0.30, 95% CI 0.16-0.54). There was no difference in analgesia requirement in labour, or in mode of delivery. There were no adverse neonatal outcomes associated with the use of misoprostol. Women in the misoprostol group experienced more pain in the interval between induction and being given analgesia in labour, but this did not reach statistical significance.\n Misoprostol 50 microg vaginally is a more effective induction agent than 1 mg dinoprostone vaginal gel, with no apparent adverse effects on mode of delivery, or on the fetus. The higher pain scores in the misoprostol group must be balanced against the reduction in time spent having labour induced, and the reduction in need for intravenous oxytocin augmentation. Further randomised studies must continue to exclude the possibility of rare adverse side effects.",
"To compare the effects of 50 microg of vaginal misoprostol with 25 microg for labor induction at term.\n One hundred and forty-seven pregnant women with indications for labor induction and cervical Bishop's score of < or = 6 were randomly assigned to receive either 50 microg (n = 74) or 25 microg (n = 73) of vaginal misoprostol every four hours until either a Bishop's score of > or = 8 or adequate uterine contraction frequency had been achieved. Induction-to-vaginal-delivery time was considered the primary outcome measure.\n Mean induction-to-vaginal-delivery time was significantly shorter in the 50-microg group than in the 25-microg group (526 +/- 141 min vs 745 +/- 218 min, respectively); oxytocin was administered to 65.8% of the patients in the 25-microg group and to 35.1% in the 50-microg group (p < .05). The incidence of tachysystole was significantly higher in the 50-microg group than in the 25-microg group (12% vs 2.7%, p < .05). We found no statistically significant difference between the two groups with respect to the rate of primary cesarean section, incidence of hyperstimulation syndrome, or neonatal outcome (p > .05).\n Fifty micrograms of vaginally administered misoprostol is an effective and inexpensive means of inducing labor at term. Uterine tachysystole may be associated more frequently with a 50-microg dose of vaginal misoprostol than with a 25-microg dose. Clinicians must accurately document the frequency and intensity of uterine contractions before every 50-microg dose of misoprostol is administered.",
"To assess the ability of a controlled-release misoprostol vaginal insert to induce labor using dose reservoirs of 25, 50, 100, and 200 microg.\n This double-blind, dose ranging, randomized study was carried out in parous women requiring induction of labor at term. Each woman was randomly assigned to receive a single misoprostol vaginal insert that could remain in place for up to 24 hours and was removed for onset of active labor, an adverse event, or having reached 24 hours in situ. The primary outcome measure was time from insertion of the misoprostol vaginal insert to vaginal delivery of the neonate.\n A total of 124 women participated in the study. The median time to vaginal delivery was 27.5, 19.1, 13.1, and 10.6 hours for the 25-, 50-, 100-, and 200-microg doses, respectively. The percentage of women who delivered vaginally within 12 hours was 9%, 14%, 47%, and 53% (P<.001 using the 25-microg group as the comparator) and within 24 hours was 42%, 79%, 81%, and 70% (P=.003). Uterine hyperstimulation syndrome occurred in one woman who received the 25-mug, two women who received the 100-microg, and three women who received the 200-microg dose reservoirs.\n Misoprostol vaginal inserts effectively induced labor in pregnant parous women at term.\n I.",
"To compare the efficacy and safety of one single dose of 50 pg misoprostol to one single dose of 3 mg dinoprostone administered vaginally for pre-induction cervical ripening in term-pregnant women, who had indications for induction of labor with unripe cervices.\n A randomized double-blind controlled trial.\n Bangkok Metropolitan Administration Medical College and Vajira Hospital, Bangkok, Thailand.\n One hundred and forty-three singleton pregnant women of > or = 37 weeks of gestation, who had indications for termination of pregnancy. All patients had a Bishop score of 0-6, without contraindications for labor induction.\n The subjects were stratified by parity to nullipara and multipara group. The subjects in each stratum were allocated by randomization to receive a single dose of 50 microg misoprostol or 3 mg dinoprostone, administered vaginally. Twenty-four hours after medication, oxytocin augmentation was given to both groups. Main outcome measure: The Bishop score of cervix at 24 hours after insertion of the studied drugs, the occurrence of abnormal uterine contraction, and the number of vaginal deliveries within 24, 48 hours.\n The demographic data and the initial Bishop score (median score 3.5 versus 4.0) were comparable in both groups. The change of score at 24 hours was one unit higher in misoprostol-treated patients compared with dinoprostone-treated patients (mean change score 6.5 versus 5.5, with 95 per cent CI 0.04 to 2.1, p=0.042) but was not of clinical importance. There was a higher frequency of hyperstimulation syndrome in the misoprostol group (6.9% vs 0%) during 8 hours of cervical ripening. Although the difference was not statistically significant (p=0.058), it was clinically important. Comparing vaginal deliveries between the misoprostol and dinoprostone groups, the frequencies of delivery within 24 hours were 46.3 per cent versus 35.7 per cent (p=0.350), and within 48 hours were 88.9 per cent versus 89.3 per cent (p>0.05), non-significantly different. No significant differences were noted between misoprostol and dinoprostone in terms of interval from start of medication to vaginal delivery and neonatal outcomes.\n The efficacy of a single 50 microg dose of vaginally administered misoprostol, is not clinically different to 3 mg dinoprostone in cervical ripening. Although the study was not sufficiently large to detect the differences in abnormal uterine contractions between the two groups, there was a higher frequency of hyperstimulation syndrome in the misoprostol group compared to the dinoprostone group. Close utero-fetal monitoring in misoprostol-treated patients is needed.",
"To compare the safety and efficacy of misoprostol with that of dinoprostone for the induction of labour at term, or near term.\n Three hundred and ninety-six women with term pregnancies were randomised to receive either oral or vaginal misoprostol, or dinoprostone. Women who had had a previous caesarean section (CS) or those with a malpresentation or who were parity > or = 5, were excluded. The control group received dinoprostone 1 mg inserted in the posterior fornix and repeated 6-hourly to a maximum of three doses. The study group received either oral misoprostol 20 micrograms 2-hourly to a maximum of four doses (80 micrograms), or vaginal misoprostol 25 micrograms in the posterior fornix with a switch to the oral misoprostol regimen if there was no change in the Bishop's score or no palpable uterine contractions.\n There was no significant difference in vaginal delivery rate within 24 hours between the groups (58.1% v. 58%, p = 0.633). There were no significant differences in CS rates between the groups; however, more CSs were performed for fetal distress in the misoprostol group than in the dinoprostone group (28% v. 25%). There was a significantly higher incidence of hyperstimulation in the vaginal misoprostol group (21.4%) than in the other two groups (oral misoprostol 16.5%, dinoprostone 8.9%) (p = 0.004). The incidence of meconium staining of liquor was comparable between the groups.\n In selected women, the efficacy of misoprostol for the induction of labour at term is similar to that of dinoprostone but misoprostol is associated with a higher incidence of hyperstimulation.",
"Our purpose was to compare the safety and effectiveness of intravaginally administered misoprostol at doses of 25 micrograms and 50 micrograms for indicated labor induction in patients with an unfavorable cervix.\n Three hundred ninety-nine patients received either 25 micrograms or 50 micrograms of misoprostol, placed intravaginally in the posterior fornix, in this randomized double-blind trial. The dose was repeated every 3 hours until adequate labor was achieved (at least three contractions in 10 minutes).\n Among 399 patients evaluated, 192 patients were allocated to the 25 micrograms group and 207 patients to the 50 micrograms group. The start-to-delivery interval was shorter in the 50 micrograms group (826 minutes vs 970 minutes, p = 0.02). The incidence of vaginal delivery after one dose was higher in the 50 micrograms group (38.2% vs 25.0%, p = 0.007). Patients receiving 25 micrograms required oxytocin augmentation more frequently than did those receiving 50 micrograms (27.1% vs 16.9%, p = 0.02). No differences were noted in the cesarean or other operative delivery rates among patients in the two treatment groups. The incidence of newborns with a cord pH < 7.16 was greater in the 50 micrograms group (13.0% vs 6.8%, p = 0.04). Although the incidence of hyperstimulation was similar between the groups, the incidence of tachysystole was higher in the 50 micrograms group (32.8% vs 15.6%, p = 0.0001).\n Although a dose of 50 micrograms is associated with a shorter start-to-delivery interval and a higher incidence of vaginal delivery after one dose, 25 micrograms of intravaginal misoprostol is effective and associated with a lower incidence of tachysystole and cord pH values < 7.16.",
"Our purpose was to compare the safety and efficacy of intravaginal misoprostol versus intracervical prostaglandin E2 (dinoprostone) gel for preinduction cervical ripening and induction of labor.\n One hundred thirty-five patients with indications for induction of labor and unfavorable cervices were randomly assigned to receive either intravaginal misoprostol or intracervical dinoprostone. Fifty microgram tablets of misoprostol were placed in the posterior vaginal fornix every 3 hours for a maximum of six doses. Prostaglandin E2 in gel form, 0.5 mg, was placed into the endocervix every 6 hours for a maximum of three doses. Medication was not given after either spontaneous rupture of membranes or beginning of active labor.\n Among 135 patients enrolled, 68 received misoprostol and 67 received dinoprostone. The average interval from start of induction to vaginal delivery was shorter in the misoprostol group (903.3 +/- 482.1 minutes) than in the dinoprostone group (1410.9 +/- 869.1 minutes) (p < 0.001). Oxytocin augmentation of labor occurred more often in the dinoprostone group (65.7%) than in the misoprostol group (33.8%) (p < 0.001). There were no significant differences between routes of delivery. Ten of the misoprostol-treated patients (14.7%) and 13 of the dinoprostone-treated patients (19.4%) had cesarean deliveries. There was a higher prevalence of tachysystole (six or more uterine contractions in a 10-minute window for two consecutive 10-minute periods) in the misoprostol group (36.7%) than in the dinoprostone group (11.9%) (p < 0.001). However, there were no significant differences in frequency of uterine hyperstimulation or hypertonus. There was a higher prevalence of meconium passage in the misoprostol group (27.9%) than in the dinoprostone group (10.5%) (p < 0.05). There was no significant difference in frequency of abnormal fetal heart rate tracings, 1- or 5-minute Apgar scores < 7, neonatal resuscitations, or admissions to the neonatal intensive care unit between the two groups.\n Vaginally administered misoprostol is an effective agent for cervical ripening and induction of labor; however when given at this dosage, it is associated with a higher prevalence of tachysystole and meconium passage than is dinoprostone. Further studies to compare the safety of misoprostol to that of dinoprostone and to delineate an optimal dosing regimen for misoprostol are needed.",
"It is known that when misoprostol is given at 200 microg every 3 h after mifepristone pretreatment, the vaginal route is more effective than the oral route. However, women prefer the oral route. This randomized study was to test our hypothesis that oral misoprostol 400 microg is as effective as vaginal misoprostol 200 microg when given every 3 h in termination of second trimester pregnancy after priming with mifepristone. A total of 142 patients was randomly assigned to group 1 (200 mg mifepristone + 400 microg oral misoprostol every 3 h up to five doses) or group 2 (200 mg mifepristone + 200 microg vaginal misoprostol every 3 h up to five doses). The incidence of side-effects and the preference study were assessed through a standardized questionnaire during and after the abortion. For the oral group, both the incidence of diarrhoea (40.0 versus 23.2%, P = 0.03) and the amount of drug used (1734 compared with 812 microg, P < 0.0001) were significantly higher than that of the vaginal group but the incidence of fever appeared to be lower (not significant). There was no significant difference in complete abortion rate: 81.4% in the oral group and 75.4% in the vaginal group. The median induction-abortion interval was similar in the two groups (10.4 versus 10.0 h). The percentage of women who aborted in 24 h was also similar: 57/70 (81.4%) in the oral group and 58/69 (87.0%) in the vaginal group. Overall, 82.0% of women preferred the oral route. Oral misoprostol (400 microg) given every 3 h up to five doses, when combined with mifepristone, was as effective as the vaginal (200 microg) route in second trimester termination of pregnancy. This regimen could also be offered to those women who found repeated vaginal administration unacceptable.",
"Our purpose was to compare vaginally administered misoprostol (Cytotec) with intravenous oxytocin for labor induction in women with premature rupture of membranes beyond 36 weeks' gestation.\n Two hundred subjects with rupture of membranes without labor were randomly assigned to receive vaginally administered misoprostol or intravenous oxytocin. Twenty-five micrograms of misoprostol (Cytotec) was placed in the posterior vaginal fornix. If cervical ripening (Bishop score of > or = 8 or cervical dilatation of > or = 3 cm) or active labor did not occur, a single repeat dose of misoprostol was given 6 hours later. Oxytocin was administered intravenously by a standardized incremental infusion protocol to a maximum dose of 22 mU per minute.\n Of the 197 subjects evaluated, 98 received misoprostol and 99 oxytocin. The average interval from start of induction to vaginal delivery was about 1 hour longer in the misoprostol group (811.5 +/- 511.4 minutes) than in the oxytocin group (747.0 +/- 448.0 minutes) (P = .65, log transformed data). Oxytocin administration was necessary in 37 of 98 (37.8%) of misoprostol-treated subjects. Vaginal delivery occurred in 85 misoprostol-treated subjects (86.7%) and 82 (85.9%) oxytocin-treated subjects (relative risk 1.17, 95% confidence interval 0.78 to 1.78, P = .45) with the remainder undergoing cesarean birth. There was no difference in the incidence of tachysystole (six or more uterine contractions in a 10-minute window for two consecutive 10-minute periods) or hypertonus between the two groups. There was no significant difference in frequency of abnormal fetal heart rate tracings between the two groups (29.6% in the misoprostol group and 28.9% in the oxytocin group, P = .91). Chorioamnionitis was diagnosed in 28 (28.6%) misoprostol-treated subjects and 26 (26.3%) oxytocin-treated subjects (P = .72, relative risk 1.06, 95% confidence interval 0.78 to 1.45). No significant differences were found in the incidence of fetal meconium (8.1% and 9.1%), 1- or 5-minute Apgar scores < 7 (11.0% and 10.2% of 1-minute Apgar scores, and 2.0% and 2.0% of 5-minute Apgar scores), neonatal resuscitation (24.5% and 27.6%), or admission to the neonatal intensive care unit (25.5% and 32.3%) between the two groups.\n Vaginal administration of misoprostol (Cytotec) is an effective alternative to oxytocin infusion for labor induction in women with premature rupture of the membranes near term. The incidence of untoward effects is similar with use of the two agents.",
"To compare the efficacy of vaginal misoprostol (25 microg) to oral misoprostol (100 microg) in labor induction at term.\n One hundred and one women at term, with indications for labor induction and cervical Bishop's scores of less than 8, were randomly assigned to receive 100 microg of oral misoprostol or 25 microg vaginal misoprostol after random allocation. This could be repeated every 4 h to a maximum of five doses. The number delivering vaginally within 24 h of the induction was the main outcome measure.\n Of those who delivered vaginally (74.5% in the oral group vs. 72% in the vaginal group), significantly fewer women delivered within 24 h of induction in the oral group (42.1% vs. 72.2%, RR 0.6, 95% CI 0.4-0.9), with more women receiving more than one dose (45.7% vs. 16.7%, RR 2.7, 95% CI 1.2-6.0). More women in the oral group received oxytocin (68.6% vs. 44%, RR 1.6, 95% CI 1.1-2.2), and the induction to delivery interval was shorter in the vaginal group, although this was not statistically significant [28.9 h (SD 20.2) vs. 20.6 h (SD 16.1), mean difference - 8.3 h, 95% CI - 16.8 to 0.2]. There were no differences in the modes of delivery, uterine hyperstimulation rates or in the neonatal outcomes.\n Vaginal misoprostol in its currently recommended dose of 25 microg seems to be more efficacious than the 100 microg oral dose.",
"The purpose of this study was to compare the efficacy and safety of stepwise oral misoprostol vs vaginal misoprostol for cervical ripening before induction of labor.\n Two hundred and four women between 32 to 42 weeks of gestation with an unfavorable cervix (Bishop score < or = 6) and an indication for labor induction were randomized to receive oral or vaginal misoprostol every 4 hours up to 4 doses. The oral misoprostol group received 50 microg initially followed by 100 microg in each subsequent dose. The vaginal group received 25 microg in each dose. The primary outcome was the interval from first misoprostol dose to delivery. Patient satisfaction and side effects were assessed by surveys completed after delivery.\n Ninety-three (45.6%) women received oral misoprostol; 111 (54.4%) received vaginal misoprostol. There was no difference in the average interval from the first dose of misoprostol to delivery in the oral (21.1 + 7.9 hrs) and vaginal (21.5 + 11.0 hrs, P = NS) misoprostol groups. The incidence of hyperstimulation in the oral group was 2.2% vs 5.4% in the vaginal group, P = NS. Eighteen patients in the oral group (19.4%) and 36 (32.4%) in the vaginal group underwent cesarean section (P < .05). This difference was attributed to better tolerance of more doses of misoprostol by the women in the oral group. There was no difference in side effects (nausea, vomiting, diarrhea, shivering) between groups. Fourteen percent of women in the vaginal group versus 7.5% in the oral group were dissatisfied with the use of misoprostol (P = NS).\n Stepwise oral misoprostol (50 microg followed by 100 microg) appears to be as effective as vaginal misoprostol (25 microg) for cervical ripening with a low incidence of hyperstimulation, no increase in side effects, a high rate of patient satisfaction, and is associated with a lower cesarean section rate.",
"The study was undertaken to compare the efficacy, safety, and maternal satisfaction of oral misoprostol and intravenous oxytocin for labor induction in women with premature rupture of membranes at term.\n One hundred five women were stratified by parity and randomly assigned to oral misoprostol 75 microg every 4 hours as needed to establish labor or to intravenous oxytocin.\n The induction to vaginal delivery time with oral misoprostol was 737 (+/-426) minutes compared with 573 (+/-318) minutes with oxytocin (P=.04). The incidence of hyperstimulation was lower in the misoprostol group (6.0% vs 27.1%, P=.005). Women were more likely to be very satisfied with their care in the misoprostol group (86.0% vs 63.4%, P=.02).\n In women at term with premature rupture of membranes, oral misoprostol resulted in a longer induction to vaginal delivery interval but increased maternal satisfaction and less hyperstimulation compared with intravenous oxytocin. Further research is needed to assess uncommon neonatal and maternal outcomes.",
"Our purpose was to compare the safety and efficacy of intravaginally administered misoprostol versus prostaglandin E2 for labor induction in a double-blind, randomized trial.\n One hundred three patients with indications for labor induction (including prelabor rupture of membranes) were randomized and received either misoprostol 50 micrograms or prostaglandin E2 (dinoprostone) 3 mg intravaginally. The dose was repeated 6, 24, and 30 hours after the first dose until active labor was achieved. For proper blinding, the drugs were prepared as identical-looking vaginal tablets.\n With use of a random number-generated table 52 patients were allocated to the misoprostol group and 51 to the prostaglandin E2 group. After exclusion of 3 patients, 50 in each group were evaluated. Delivery within 24 hours after administration occurred more often in the misoprostol group (70% vs 46% in the prostaglandin E2 group, p = 0.009), and fewer patients in this group needed more than two doses (12% vs 30%, p = 0.027). No difference in cesarean section rate (12% vs 14%, p = 0.67), fetal heart rate anomalies (33% vs 34%, p = 0.89), tachysystole (8% vs 14%, p = 0.37), hyperstimulation syndrome (0% vs 2%, not significant), meconium passage (28% vs 18%, p = 0.22), and fetal outcome (Apgar score at 1 and 5 minutes, arterial and venous umbilical cord blood pH, transfer to neonatal intensive care unit) was noted between the two groups.\n Intravaginal misoprostol is a safe drug for labor induction with superior effectiveness compared with intravaginal prostaglandin E2.",
"To compare the efficacy and safety of titrated oral misoprostol and vaginal misoprostol for labor induction.\n Women between 34 and 42 weeks of gestation with an unfavorable cervix (Bishop score less than or equal to 6) and an indication for labor induction were randomLy assigned to receive titrated oral or vaginal misoprostol. The titrated oral misoprostol group received a basal unit of 20 mL misoprostol solution (1 mcg/mL) every 1 hour for four doses and then were titrated against individual uterine response. The vaginal group received 25 mcg every 4 hours until attaining a more favorable cervix. Vaginal delivery within 12 hours was the primary outcome. The data were analyzed by intention-to-treat.\n Titrated oral misoprostol was given to 101 (48.8%) women and vaginal misoprostol to 106 (51.2%) women. Completed vaginal delivery occurred within 12 hours in 75 (74.3%) women in the titrated oral group and 27 (25.5%) women in the vaginal group (relative risk [RR] 8.44, 95% confidence interval [CI] 4.52-15.76). The incidence of hyperstimulation was 0.0% in the titrated oral group compared with 11.3% in the vaginal group (RR 0.08, 95% CI 0.01-0.61). Although more women experienced nausea (10.9%) in the titrated oral group (RR 27.07, 95% CI 1.57-465.70), fewer infants had Apgar scores of less than 7 at 1 minute in the titrated oral group than in the vaginal group (RR 0.10, 95% CI 0.01-0.76).\n Titrated oral misoprostol is associated with a lower incidence of uterine hyperstimulation and a lower cesarean delivery rate than vaginal misoprostol for labor induction in patients with unfavorable cervix.\n ClinicalTrials.gov, www.clinicaltrials.gov, NCT00529295\n I.",
"To compare the efficacy and patient acceptability of 50 microg of sublingual misoprostol with 100 microg of oral misoprostol in the induction of labour at term.\n Non-blinded randomised comparative trial.\n Tertiary level UK Hospital.\n Two hundred and fifty women at term with indications for labour induction.\n Fifty micrograms of sublingual misoprostol or 100 microg of oral misoprostol was administered every four hours after random allocation, to a maximum of five doses.\n Number of patients delivering vaginally within 24 hours of the induction, mode of delivery, neonatal outcomes and patient acceptability.\n There was no significant difference in the number of women delivering vaginally within 24 hours of the induction in the sublingual group as compared with the oral group (62.8% vs 59%, RR 1.1, 95% CI 0.6-2.1), or in the mean induction to delivery time (21.8 vs 24.1 h, mean difference 2.3 h 95% CI -2.2 to +6.7). There was no difference in the uterine hyperstimulation rates (1.6% in both groups), operative delivery rates or neonatal outcomes. In the sublingual group, 92.6% found the induction acceptable with 15.8% finding the tablets with an unpleasant taste, while in the oral group it was 96.9% and 4%, respectively. More patients in the oral group thought that they would consider the same method of induction again as compared with the sublingual group (58.6% vs 40%, RR 1.4, 95% CI 1.04-1.9).\n Fifty micrograms of sublingual misoprostol every four hours has the same efficacy and safety profile as compared with 100 microg orally, but the oral route might be preferred by women.",
"To evaluate the effectiveness and safety of the vaginal application of misoprostol for induction of labor at term, with the interval duration from labor induction to vaginal birth as the primary outcome measure.\n Two hundred twenty-two women with indications for induction of labor at term were randomized to receive either misoprostol 50 micrograms per vagina every 4 hours as needed or our standard approach (physician-chosen combinations of intracervical or vaginal dinoprostone every 6 hours, artificial rupture of membranes, and oxytocin infusion).\n Mean (+/-standard deviation) time to vaginal delivery was 753 +/- 588 minutes for misoprostol versus 941 +/- 506 minutes for the physician-chosen combination (P = .018). Oxytocin infusion was used less frequently (relative risk [RR] 0.48, 95% confidence interval [CI] 0.31-0.74). There was no significant difference in cesarean rate or maternal morbidity. Neonatal outcomes, including cord-blood acid-base analysis, were not significantly different. The estimated cost per patient in Canadian dollars for prostaglandins was $0.22 with misoprostol and $70.00 with standard therapy.\n Vaginal misoprostol is a cost-effective alternative to current labor-induction protocols. We found no evidence of harm to mother or newborn in substantive outcomes.",
"Various methods have been described for preoperative cervical priming prior to vacuum aspiration (VA) in first trimester pregnancy termination, to facilitate cervical dilatation and shorten the abortion procedure. Recently misoprostol a prostaglandin E1 analogue has been shown to be effective in facilitating cervical dilatation prior to VA. Misoprostol offers several advantages over the other prostagland in analogues including stability at room temperature, ease of administration and minimal side effects.\n To determine the optimal dosage and dosing interval for the use of misoprostol administered sublingually for pre-abortion cervical dilatation.\n This was a prospective randomised study conducted at Comprehensive Rural Health Project, Ballabgarh the rural health centre under Centre for Community Medicine, AIIMS, New Delhi.\n One hundred and twenty pregnant women between 6-11 weeks of gestation opting for voluntary medical termination of pregnancy were (MTP) randomly allocated to either 200 microg or the 400 microg misoprostol group. Vacuum aspiration was performed either two or three hours after administration of sublingual misoprostol. Using Hegar's dilators, degree of cervical dilatation before vacuum aspiration was measured. Other parameters assessed included the amount of additional dilatation required, intra-operative blood loss and associated side effects.\n Statistical analysis was conducted using chisquare, the student's t and the Mann-Whitney U tests to examine the difference between the two groups.\n In the 200 microg misoprostol group 33% achieved a dilatation of > or = 8 mm compared with 71% of women in the 400 microg misoprostol group. The odds ratio was 95.8 (95% CI 10.2-842.9) for 400 microg misoprostol for successful preoperative cervical dilatation of > or = 8 mm. The mean baseline cervical dilatation for 400 microg and 200 microg misoprostol was 8.2 mm and 6.0 mm respectively (P < 0.001). The use of 400 mg misoprostol with an evacuation interval of two hours appears to be the optimal dosage and evacuation interval. Increasing the time interval beyond two hours did not confer any additional advantage on the rate of successful cervical dilatation but was instead associated with an increased incidence of side effects such as preoperative vaginal bleeding, abdominal pain and shivering.\n Our study has shown that Sublingual administration of 400 microg of misoprostol at least two hours before procedure is effective for preoperative cervical dilatation before vacuum aspiration in first trimester pregnancy termination. There is no additional advantages of increasing the dosing interval upto three hours.",
"To compare the efficacy of vaginal and oral misoprostol for the induction of labour in women with intra-uterine foetal death (IUFD).\n A prospective randomised clinical trial, comparing 200 microg oral and 200 microg vaginal misoprostol, six hourly for a maximum of four doses for the induction of labour in women with IUFD.\n Ga-Rankuwa hospital (Department of Obstetrics and Gynaecology), Pretoria, South Africa. It is a tertiary institution serving predominantly black indigenous population.\n The primary outcome measure was the induction to delivery time, and secondary outcome measures were the number of patients requiring augmentation with oxytocin and all complications were noted.\n Twenty women were randomised to the vaginal route and 18 to the oral route. The induction to delivery time was shorter with vaginal misoprostol (13.5 +/- 8.3 hrs) compared to oral misoprostol (21.4 +/- 13.9 hrs; p < 0.05). There was no significant difference in the amount of misoprostol needed to achieve successful induction in the two groups. More women (10/18) who received oral misoprostol required oxytocin augmentation to complete the induction of labour compared with 4/20 women in the vaginal group (p < 0.05; Odds Ratio 2.8; 95% Cl 1.36 - 4.24). There were no cases of failed induction. The systemic side effects (shivering, diarrhoea, vomiting and pyrexia) were more common with oral misoprostol (44.5%) compared to vaginal misoprostol (20%). This difference gives an overall Odds Ratio of 2.2 at 95% Cl of 1.6-2.8(p < 0.05).\n Vaginal misoprostol achieved successful induction of labour in women with IUFD in a shorter time than oral misoprostol with significantly less side effects.",
"Our purpose was to compare the efficacy of 25 microg and 50 microg intravaginally administered misoprostol tablets for cervical ripening and labor induction. Either 25-microg (n: 58) or 50-microg (n: 56) misoprostol tablets were randomly administered intravaginally to 114 subjects with an unripe cervix for labor induction. The physician was blinded to the medication. Intravaginal misoprostol was given every 4 h until the onset of labor. The mean Bishop score before misoprostol administration was 2.1 +/- 1.6 in the 25-microg group and 2.0 +/- 1.4 in the 50-microg group (p > 0.05). With the 25-microg dose the time until delivery was significantly longer (991.2 +/- 514.4 min vs. 703.12 +/- 432.6 min in the 50-microg group). The use of oxytocin augmentation was significantly higher in the 25-microg group (63.8%) than the 50-microg group (32.1%; p < 0.05). The proportions of patients with tachysystoles and hypersystoles were not significantly different between the two groups (19 and 6.9%, respectively, in the 25-microg group and 25 and 17.8%, respectively, in 50-microg group; p > 0.05). Overall, in the 25-microg group more women achieved vaginal delivery (79.3 vs. 60.7%; p < 0.05). The rate of cesarean sections due to non-reassuring fetal status was higher in the 50-microg misoprostol group (28.6 vs. 10.3%; p < 0.05). The number of neonates with a low 1-min Apgar score (<7) was significantly higher in the 50-microg misoprostol group (26.8 vs. 8.6%; p < 0.05), but 5-min Apgar scores and umbilical artery blood gas values at the time of delivery were not significantly different between the groups (p > 0.05). One patient in the 25-microg group suffered a ruptured uterus. Intravaginal administration of 25 microg of misoprostol is a clinically effective labor induction regimen and has the least adverse effects and complications.\n Copyright 2002 S. Karger AG, Basel",
"Our purpose was to compare the safety and efficacy of intravaginal misoprostol versus intracervical prostaglandin E2 gel (dinoprostone) for preinduction cervical ripening and induction of labor.\n Two hundred seventy-six patients with indications for induction of labor and unfavorable cervices were randomly assigned to receive either intravaginal misoprostol or intracervical dinoprostone. Twenty-five micrograms of misoprostol were placed in the posterior vaginal fornix every 3 hours, with a potential maximum of eight doses. Prostaglandin E2 in gel form, 0.5 mg, was placed in the endocervix every 6 hours, with a maximum of three doses. Further medication was withheld with the occurrence of spontaneous rupture of membranes, entry into active phase of labor, or a \"prolonged contraction response.\"\n Among those evaluated, 138 received misoprostol and 137 received dinoprostone. The average interval from start of induction to vaginal delivery was shorter in the misoprostol group (1323.0 +/- 844.4 minutes) than in the dinoprostone group (1532.4 +/- 706.5 minutes) (p < 0.05). Need for oxytocin augmentation of labor occurred more commonly in the dinoprostone group (72.6%) than in the misoprostol group (45.7%) (p < 0.0001). There were no significant differences in the routes of delivery. Twenty-eight of the misoprostol-treated patients (20.3%) and thirty-eight of the dinoprostone-treated patients (27.7%) required abdominal delivery. Complications such as uterine tachysystole and thick meconium passage occurred with similar frequency in the two treatment groups.\n Intravaginal administration of misoprostol appears to be as effective as intracervical dinoprostone for cervical ripening and labor induction. Complications associated with prostaglandin administration were not statistically different between the two treatment groups. The cost of misoprostol ($0.36/100 micrograms) is much less than that of dinoprostone ($75/0.5 mg).",
"A prospective randomised controlled trial was undertaken to compare the efficacy of two routes of administration, oral versus vaginal, of the prostaglandin E1 analogue misoprostol (Cytotec) to effect termination of pregnancy in the mid-trimester. Fifty-five women were recruited into the trial; 26 to receive all doses orally and 29 via the vaginal route. The dosing regimen was 400 microg as the initial dose followed by a second dose of 200 microg two hours later and then four-hourly 200 microg doses until delivery or 32 hours from commencement of treatment. If delivery had not been effected by the last dose of misoprostol, a Syntocinon infusion was started synchronously Misoprostol administered vaginally was significantly more effective than when administered orally as judged by induction-to-delivery interval and also the need or otherwise to augment therapy with a Syntocinon infusion. The average induction-to-delivery interval was 17.5 hours in the vaginal group compared to 33 hours in the oral group (p = 0.0003). The percentages of women who delivered at 24 and 48 hours were 93% and 100% in the vaginal administration group and 19% and 70% in the oral administration group (p < 0.05). No significant differences in complication rates or side effects were noted between the two groups",
"To compare the effectiveness of 25 microg vs. 50 microg of intravaginal misoprostol for cervical ripening and labor induction beyond 41 weeks' gestation.\n The study population consisted of 120 women not in active labor with a gestational age >41 weeks, singleton pregnancy with vertex presentation, reactive fetal heart rate tracing, amniotic fluid index >/=5, and Bishop score <5. Women were randomized to receive either 25 microg (n=60) or 50 microg (n=60) of intravaginal misoprostol. The dose was repeated every 4 h (maximum number of doses limited to six) until the patient exhibited three contractions in 10 min. The main outcome measure was the induction-vaginal delivery interval.\n There was no significant difference between the two groups with regard to the induction-vaginal delivery interval (685+/-201 min in the 25 microg group vs. 627+/-177 min in the 50 microg group, P=0.09). The proportion of women delivering vaginally with one dose of vaginal misoprostol was significantly greater in the 50 microg group (0/49 vs. 41/47, P<0.001). There were no differences in the rates of cesarean and operative vaginal delivery rates, or in the incidences of tachysystole and hyperstimulation syndrome in the two treatment groups. Neonatal outcomes were also similar.\n Intravaginal administration of 25 microg of misoprostol appears to be as effective as 50 microg for cervical ripening and labor induction beyond 41 weeks' gestation.",
"To compare the efficacy, side effects, and complications of high-dose vaginal misoprostol with concentrated intravenous oxytocin plus low-dose vaginal prostaglandin (PGE(2)) for second-trimester labor induction.\n One hundred twenty-six consenting women with maternal or fetal indications for pregnancy termination and no prior cesarean delivery were randomly assigned to receive either vaginal misoprostol 600 microg 1x, 400 microg every 4 hours 5x (misoprostol group, n = 60) or escalating-dose concentrated oxytocin infusions (277-1,667 mU/min) plus vaginal PGE(2) 10 mg every 6 hours 4x (oxytocin group, n = 66). Both groups received concurrent extra-amniotic saline infusion for cervical ripening. Women who failed their assigned regimen received 20 mg of PGE(2) suppositories every 4 hours until delivery. Analysis was by intent to treat.\n Demographic characteristics were similar between study groups. Median induction-to-delivery interval was significantly shorter in the misoprostol group (12 hours) than in the oxytocin group (17 hours; P <.001). There was a higher induction success rate at 24 hours in the misoprostol group (95%) than in the oxytocin group (85%; P =.06), although this difference did not reach statistical significance. The incidence of live birth (25% versus 17%), chorioamnionitis (5% versus 2%), and postpartum hemorrhage greater than 500 mL (3% versus 3%) were similar between the misoprostol and oxytocin groups, respectively. Diarrhea (2% versus 11%; P =.04), nausea/emesis (25% versus 42%; P =.04), and retained placenta requiring curettage (2% versus 15%; P =.008) were significantly less common in the misoprostol group when compared with the oxytocin group, respectively. Isolated intrapartum fever, however, was more frequent in the misoprostol group (67%) than in the oxytocin group (21%; P <.001).\n Compared with concentrated oxytocin plus low-dose vaginal PGE(2), high-dose vaginal misoprostol is associated with significantly shorter induction-to-delivery intervals, fewer side effects, a lower incidence of retained placenta, and comparable incidence of live birth.",
"The aim of this randomized controlled study was to compare the efficacy and the safety of different regimens of misoprostol for labor induction. MATERIALS AND METHODS Eligible women received intravaginal 100 microg, every 6 h or 50 microg every 4 h. Treatment continued until: (1) dilatation >3 cm; (2) rupture of membranes (artificial); (3) signs of uterine hyperstimulation; (4) adequate contraction pattern (three contraction/10 min). Managing clinician might use oxytocin during labor. Cesarean section rate was the main outcome that was considered variably. Other outcome measures were neonatal outcome (Apgar scores, meconium staining, and umbilical artery pH) and induction to delivery interval.\n A total number of 72 women received either misoprostol 100 microg (n=37), or 50 microg (n=35) randomly. The two groups had similar mean Bishops scores at induction (4.10+/-2.4 versus 4.2+/-2.1; P=0.85), rates of nulliparity, use of epidural anesthesia, and oxytocin augmentation. In two groups the number of doses of misoprostol used was similar (1.6+/-0.5 versus 1.7+/-0.3)\n There was not any difference between the two groups in the mean+/-S.D. time to delivery (h) and cesarean rate. Likewise, there was not a significance between two groups in the rates of 5 min Apgar score, and of meconium passage.",
"The aim of this randomized study was to compare the effectiveness, safety, and side effects of 6 h vaginal misoprostol versus vaginal prostaglandin E(2) (PGE(2)) for labor induction.\n Fifty microgram of misoprostol was given intravaginally in the misoprostol group (204 women), and 3 mg PGE(2) was given intravaginally in the PGE(2) group (211 women). In both groups, the dose was repeated every 6 h for a maximum of three doses, until active labor was achieved. Artificial rupture of membranes and oxytocin infusion was used during labor in both groups where it was indicated.\n The mean interval from the institution of labor induction to delivery was 11.3 +/- 8.6 h for the misoprostol group, and 15.7 +/- 9.3 h for PGE(2 )group (P < 0.05). In the misoprostol group, oxytocin was used less frequently, but there was a higher prevalence of tachysystole. No statistically significant differences were observed between the two groups as regard abnormal patterns of fetal heart rate, the mode of delivery, and the need for neonatal intervention.\n In conclusion, the intravaginal administration of 50 mug misoprostol at 6 h interval (maximum three doses) is comparable in safety, but more effective for induction of labor than 3 mg intravaginal PGE(2).",
"Misoprostol - a stable prostaglandin E1 analogue- is effective and safe in the induction of labour. There is paucity of information about the use of misoprostol for labour induction in Nigeria.\n To evaluate the efficacy of misoprostol in the induction of labour in the third trimester. METHODS. Consecutive patients for induction of labour were randomized into misoprostol or oxytocin study groups. The misoprostol group received intravaginal 50 microg 6- hourly to a maximum of four doses. Those in the oxytocin group received a maximum of 48 iu/min. Outcome measures included induction-delivery interval, mode of delivery, Apgar score, perinatal death and maternal complications.\n Sixty-two patients were recruited into the study-34 received misoprostol while 28 received oxytocin. The modal gestational age and Bishop score prior at induction were >36 weeks and 5-7 respectively. Hypertension in pregnancy was the commonest indication for induction of labour followed by prolonged pregnancy. The overall induction-delivery interval was 12.2 +/- 5.2 hours; Misoprostol v oxytocin, mean(range): 12.1(7-27) vs 12.3(4-27) hours, p = 0.88). There were no significant differences in the mean Apgar score and perinatal mortality rate in the two study groups. There were two cases of primary postpartum haemorrhage in the oxytocin group but none in the misoprostol group. One case of ruptured uterus was encountered in the misoprostol group. No case of maternal mortality was recorded. Four patients in the misoprostol group had minor side effects mainly nausea and vomiting.\n The efficacy of misoprostol in the induction of third trimester labour is comparable to oxytocin. The risk of ruptured uterus associated with misoprostol appears higher than that of oxytocin in the induction of labour. Further studies are needed to verify this observation in our setting.",
"To compare oral misoprostol solution with vaginal prostaglandin gel (dinoprostone) for induction of labour at term to determine whether misoprostol is superior.\n Randomised double blind placebo controlled trial.\n Maternity departments in three hospitals in Australia. Population Pregnant women with a singleton cephalic presentation at > or = 36+6 weeks' gestation, with an indication for prostaglandin induction of labour.\n 20 mug oral misoprostol solution at ourly intervals and placebo vaginal gel or vaginal dinoprostone gel at six hourly intervals and placebo oral solution.\n Vaginal birth within 24 hours; uterine hyperstimulation with associated changes in fetal heart rate; caesarean section (all); and caesarean section for fetal distress.\n 741 women were randomised, 365 to the misoprostol group and 376 to the vaginal dinoprostone group. There were no significant differences between the two treatment groups in the primary outcomes: vaginal birth not achieved in 24 hours (misoprostol 168/365 (46.0%) v dinoprostone 155/376 (41.2%); relative risk 1.12, 95% confidence interval 0.95 to 1.32; P = 0.134), caesarean section (83/365 (22.7%) v 100/376 (26.6%); 0.82, 0.64 to 1.06; P = 0.127), caesarean section for fetal distress (32/365 (8.8%) v 35/376 (9.3%); 0.91, 0.57 to 1.44; P = 0.679), or uterine hyperstimulation with changes in fetal heart rate (3/365 (0.8%) v 6/376 (1.6%); 0.55, 0.14 to 2.21; P = 0.401). Although there were differences in the process of labour induction, there were no significant differences in adverse maternal or neonatal outcomes.\n This trial shows no evidence that oral misoprostol is superior to vaginal dinoprostone for induction of labour. However, it does not lead to poorer health outcomes for women or their infants, and oral treatment is preferred by women.\n National Health and Medical Research Council, Perinatal Trials, PT0361.",
"To evaluate the safety and clinical effectiveness of intravaginal misoprostol, a synthetic prostaglandin E1 analogue, for labor induction in gravidas with premature rupture of membranes (PROM) at term.\n One hundred forty-one pregnant women with term PROM were assigned randomly to one of two induction groups: 1) intravaginal misoprostol or 2) intravenous oxytocin by continuous infusion.\n Seventy subjects were allocated to the misoprostol group and 71 to the oxytocin group. The mean (+/- standard deviation) interval from induction to delivery was significantly shorter in the misoprostol group (416 +/- 276 compared with 539 +/- 372 minutes; P = .04). In 85.7% of patients in the misoprostol group, only one dose was required. Intrapartum complication rates, mode of delivery, and neonatal or maternal adverse event rates were similar in the two treatment groups. Uterine tachysystole occurred more frequently with misoprostol than with oxytocin (28.6% compared with 14.0%; P < .04).\n Intravaginal administration of misoprostol induces labor safely and effectively in patients with PROM at term.",
"To compare the efficacy and safety of 100 microg oral misoprostol for induction of labor between the regimen of 3 hour and 6 hour interval administration.\n Singleton pregnancies indicated for induction of labor between 34 and 42 weeks of gestation in the condition of unfavorable cervix (Bishop score < or = 4) and no contraindication for prostaglandins therapy were recruited into the study. All pregnant women were randomly assigned to receive 100 microg oral misoprostol every 3 hours or 6 hours until the cervix was favorable for amniotomy, spontaneous rupture of membranes or active labor occurred.\n The mean time interval from induction to vaginal delivery was significantly shorter in the 3 hour interval group, compared with the 6 hour interval group (13.82 +/- 6.98h and 17.66 +/- 7.48h, P = 0.0019). There was no significant difference between the groups with regard to mode of delivery, analgesic requirement, maternal complication and neonatal outcome.\n 100 microg oral misoprostol every 3 hours is more effective for labor induction than every 6 hours but there was no difference in mode of delivery, analgesic requirement, maternal complications and neonatal outcome. A dose of 100 microg misoprostol orally every 3 hours seems to be the optimum regimen and the new option for labor induction. However, further study should be performed.",
"We compared the efficacy of misoprostol with that of prostaglandin E2 in cervical ripening and labour induction. Thus 238 women with rupture of membranes beyond 36 weeks gestation without labour were randomized to receive 50 microg misoprostol vaginal gel or 5 mg of prostaglandin E2 gel. Bishop score was evaluated before drug application and 6 hours later. Clinical data and perinatal outcome were recorded. Mean time from induction to delivery and the need for oxytocin were significantly less in the misoprostol group. There were no significant differences in spontaneous labour rate, type of delivery and perinatal outcome. It is concluded that intravaginal misoprostol is safe and more effective than prostaglandin E2 for preinduction cervical ripening in premature rupture of membranes beyond 36 weeks gestation.",
"Our purpose was to compare orally administered with vaginally administered misoprostol for cervical ripening and labor induction.\n Two hundred twenty subjects with medical or obstetric indications for labor induction and undilated, uneffaced cervices were randomly assigned to receive orally administered or vaginally administered misoprostol. Fifty micrograms of oral misoprostol or 25 microgram of vaginal misoprostol was given every 4 hours. If cervical ripening (Bishop score of >/=8 or cervical dilatation of >/=3) or active labor did not occur, repeated doses were given to a maximum of 6 doses or 24 hours. Thereafter, oxytocin was administered intravenously by a standardized incremental infusion protocol to a maximum of 22 mU/min.\n Of the 220 subjects evaluated, 110 received orally administered misoprostol and 110 received vaginally administered misoprostol. Fewer subjects who received the oral preparation (34/110, 30.9%) were delivered vaginally within 24 hours of initiation of induction, in comparison with those who received the vaginal preparation (52/110, 47.3%) (P =.01). The average interval from start of induction to vaginal delivery was nearly 6 hours longer in the oral treatment group (mean and SD 1737.9 +/- 845.7 minutes) than in the vaginal treatment group (mean and SD 1393.2 +/- 767.9) (P =.005, log-transformed data). Orally treated patients required significantly more doses than vaginally treated patients (orally administered doses: mean and SD 3.3 +/- 1.7; vaginally administered doses: mean and SD 2.3 +/- 1.2) (P <.0001). Oxytocin administration was necessary in 83 (75.4%) of 110 orally treated subjects and in 65 (59.1%) of 110 vaginally treated subjects (P =.01, relative risk 1. 28, 95% confidence interval 1.06-1.54). Vaginal delivery occurred in 95 (86.4%) orally treated subjects and in 85 (77.3%) vaginally treated subjects (P =.08, relative risk 1.12, 95% confidence interval 0.99-1.27), with the remainder undergoing cesarean delivery. There was no difference in the incidence of uterine contractile abnormalities (tachysystole, hypertonus, or hyperstimulation), intrapartum complications, or neonatal outcomes between the 2 groups.\n Oral administration of 50-microgram doses of misoprostol appears less effective than vaginal administration of 25-microgram doses of misoprostol for cervical ripening and labor induction. Further investigation is needed to determine whether orally administered misoprostol should be used for cervical ripening and labor induction.",
"To evaluate the efficacy, safety, and patient acceptability of sublingual misoprostol compared with an equivalent dose administered orally for labor induction at term.\n One hundred women with medical or obstetric indications for induction of labor after 37 weeks of gestation and unfavorable cervices were randomized to receive 50 microg of misoprostol either orally or sublingually. The dose was repeated every 4 hours to a maximum of 5 doses if indicated. Previous cesarean delivery was a criteria for exclusion. Our primary outcome measure was the number of patients who went on to have a vaginal delivery within 24 hours of the induction. The need for oxytocin, mode of delivery, number of cesarean deliveries for fetal distress, uterine hyperstimulation rates, and neonatal outcomes were secondary outcome measures. Patient acceptability was assessed by questionnaires completed after delivery.\n Significantly more patients were delivered of infants within 24 hours (73.8% versus 45.7%; relative risk, 1.6; 95% confidence interval, 1.1 to 2.4) and the induction to delivery intervals were significantly shorter (20 hours versus 28.3 hours; mean difference, 8.3 hours; 95% confidence interval, 1.2 to 15.4) in the sublingual group compared with the oral group. There was 1 case of uterine hyperstimulation in the sublingual group. There were no significant differences in the mode of delivery, interventions for fetal distress, or neonatal outcomes in the 2 groups. The satisfaction rates were 82.5% and 85.7% in the oral and sublingual groups respectively, and 9.5% of patients thought that the sublingual tablets did not dissolve completely.\n There has been no previous report in the literature of misoprostol given sublingually for labor induction. Sublingual misoprostol seems to have better efficacy than oral misoprostol, seems to be acceptable to patients, and is an option to be considered to induce labor at term.",
"To compare the active management of term prelabour rupture of membranes with oral misoprostol with conservative management for 24 hours followed by induction with oxytocin or prostaglandin E(2) (PGE(2)) gel.\n A non-blinded randomised controlled trial.\n Induction and labour wards, Aberdeen Maternity Hospital.\n Sixty-one women with confirmed prelabour rupture of the membranes at > or =36 weeks of gestation.\n The women were randomised to 50 microg of oral misoprostol repeated every 4 hours, if required, to a maximum of five doses (active group), or to induction of labour with PGE(2) gel or oxytocin only if not in spontaneous labour 24 hours after prelabour rupture of membranes (conservative group).\n Number of women in active labour within 24 hours of the prelabour rupture of membranes, preference of women for any one particular method of management in any subsequent pregnancy with prelabour rupture of membranes.\n 93.3% of the active group and 54.8% of the conservative group were in spontaneous labour within 24 hours of the prelabour rupture of membranes (RR 1.7, 95% CI 1.2 to 2.4). Of those achieving a vaginal delivery, 72% of the active group did so within 24 hours of the prelabour rupture of membranes as compared with 26.9% of the conservative group (RR 2.7, 95% CI 1.4 to 5.3, P = 0.002). There were no significant differences in the neonatal or maternal outcomes. In the active group, 78% felt they would have the same method of induction as compared with 40% in the conservative group (RR 1.9, 95% CI 1.1 to 3.3, P = 0.03).\n Active management with oral misoprostol resulted in more women going into labour and delivering within 24 hours of the prelabour rupture of membranes with no increase in maternal or neonatal complications. Women tended to view active management of prelabour rupture of membranes more positively. Oral misoprostol might be an option to consider in those wishing active management.",
"Intrauterine fetal death is a major problem in obstetrics particularly in developing countries such as Uganda. Induction of labour in cases of fetal death using the available method of oxytocin is often difficult, expensive and frustrating.\n To compare the effectiveness of vaginal misoprostol and intravenous oxytocin in induction of labour in women with intrauterine fetal death.\n One hundred and twenty mothers were allocated in a randomised controlled way to one of the two induction groups. Oxytocin infusion was titrated based on patient response. The starting dose was 50 mcg (1/4 tablet) in misoprostol group and the dose was doubled every six hours till effective contractions were achieved. The two groups were compared for induction to delivery intervals, costs of the drugs and their safety during induction.\n The success rate within 48 hours of induction was 100% in the misoprostol group and 96.7% in oxytocin group. The mean induction to delivery time was significantly longer in the oxytocin group compared with the misoprostol group (23.3 versus 12.4 hours; p= 0.004). In the gestational age before 28 weeks, the induction to delivery interval in oxytocin group, was more than twice that used in misoprostol. However beyond 28 weeks, there was no significant difference. Women with intact membranes had induction to delivery interval of 27.9 hours in the oxytocin group and 14.7 hours in the misoprostol group (p=0.002). When the membranes were ruptured, the values were 10.5 and 8.5 hours respectively (p=0.6). The induction to delivery time in cases with Bishop's score < 6 was 29.8 hours in the oxytocin group and 15.9 hours in misoprostol group (p=0.001). The corresponding values for Bishop's scores > 6 were 10 and 7.9 hours respectively (p=0.6). The majority of patients in misoprostol group (62%), required less than one tablet for successful induction. Misoprostol was cheaper (0.65 US dollars than oxytocin (7.86 US dollars) Retained placenta occurred in only 3.3% of the patients in the misoprostol group. There were no cases of ruptured uterus in both groups.\n Intravaginal misoprostol is more effective and cheaper than intravenous oxytocin for inducing labour in patients with intrauterine fetal death.",
"To compare the efficacy of a vaginal insert administering continuous dinoprostone with vaginal suppositories containing two different doses of misoprostol for cervical ripening and induction of labor.\n In this prospective, randomized, double-blinded study, 118 patients with indications for induction of labor and an unfavorable Bishop score were randomly assigned to receive either continuous dinoprostone, misoprostol 35-microg suppositories, or misoprostol 50-microg suppositories.\n No significant differences were noted among the three groups in the change of Bishop score, induction of active labor or the time from initial treatment to delivery. Active labor occurred in roughly two-thirds of the patients in an average of about 5.7-6.7 h regardless of treatment assignment. When the two misoprostol groups were combined, a shorter interval from insertion to vaginal delivery was observed in the nulliparous women receiving misoprostol than those receiving continuous dinoprostone (21.3 vs. 27.2 h, p = 0.019). Except for the significantly lower incidence of tachysystole observed in the combined misoprostol group (3.8% vs. 15.4%, p = 0.036), there were no other significant differences between the groups in mode of delivery or in adverse maternal, fetal, or neonatal effects.\n Misoprostol suppositories appeared to be as effective and safe as continuous dinoprostone in inducing cervical ripening in this sample.",
"Our purpose was to compare the efficacy of oral misoprostol with that of vaginal misoprostol for midtrimester termination of pregnancy.\n Women seen for midtrimester pregnancy termination were randomly assigned to receive either misoprostol orally in a dose of 200 microg every hour for 3 hours followed by 400 microg every 4 hours or vaginally in a dose of 400 microg every 4 hours. The protocol was followed for 24 hours, after which time further management was at the discretion of the attending physician. The primary outcome measure was the induction-to-delivery interval. Sample size was calculated a priori. Statistical analysis was performed with the t test for continuous variables and the chi(2) test for categorical variables. P <.05 was considered significant.\n One hundred fourteen women were randomized, with 49 receiving vaginal misoprostol and 65 receiving oral misoprostol. The two groups were comparable with respect to maternal age, parity, indication for pregnancy termination, gestational age, and maternal weight. The mean induction-to-delivery interval was significantly shorter for the vaginal group (19.6 +/- 17.5 hours vs 34.5 +/- 28.2 hours, P <.01). Length of stay was also shorter in the vaginal group (32.3 +/- 17.3 hours vs 50.9 +/- 27.9 hours, P <.01). Significantly more patients in the vaginal group were delivered within 24 hours (85.1% vs 39.5%, P <.01), and more patients in the oral group required changes in the method of induction when they were undelivered after 24 hours (38.2% vs 7%, P <.01). The only complication was an increase in febrile morbidity in the vaginal group (25% vs 6.7%, P =.046). This did not result in an increased use of antibiotics, and all the fevers resolved post partum without further complications.\n Vaginal administration of misoprostol resulted in a shorter induction-to-delivery interval. The shorter length of stay should result in improved patient care.",
"To compare the safety and efficacy of intravaginal misoprostol gel with that of tablets for ripening the cervix and inducing labor in women with unfavorable cervices.\n Four hundred sixty-seven gravidas were randomized to receive misoprostol tablets (n = 234) or misoprostol gel (n = 233). The gel was prepared in the antepartum unit immediately before use by dissolving the tablet in 1 mL normal saline and mixing with 4 mL hydroxyethylcellulose gel. In both groups, a 50-microgram dose was applied intravaginally every 8 hours for two doses, then increased to 100-microgram for a total of six applications or 500 micrograms.\n The mean interval in hours from drug administration to start induction or labor (13.8 versus 18.2) and delivery (22.4 versus 29.0) was significantly less in the tablet group than in the gel group (P < .01 for both). Oxytocin and epidural use and the mean number of misoprostol insertions (1.4 versus 1.9) were lower in the tablet group than in the gel group (P < .05 for all). The incidences of tachysystole (13.7 versus 7.3%) and hyperstimulation (15.8 versus 7.7%) were significantly higher in the tablet group than in the gel group. Cesarean delivery rates and neonatal outcomes were similar between the groups.\n Intravaginal misoprostol gel is associated with fewer uterine contractile abnormalities than the tablet form of the drug but results in a slower time to labor or delivery.",
"251 women with indications for labor induction at term were randomised to receive either 50 or 100 microgs of oral misoprostol, repeated every 4 h to a maximum of 5 doses. Parous women in the higher dose group received 50 microgs as their first dose, subsequent doses being 100 microgs. Women who failed to respond to the 5 doses of misoprostol had the option of having vaginal PGE2 gel. The primary outcome measure was the induction to delivery interval in those who delivered vaginally. Patient satisfaction was assessed by postnatal questionnaire.\n The induction to vaginal delivery interval, although shorter in the 100 microgs group was not statistically significant (26.8 versus 33.7 h, mean difference 6.9 h, 95% CI 0.4-13). There were, however, more failed inductions with misoprostol in the 50 microgs group (12.7% Vs 4.8%, RR 2.6, 95% CI 1.07-6.5). There were no differences in the modes of delivery, number of caesarean sections for fetal distress or in the neonatal outcomes in the two groups. Most patients, 83% and 92% in the 50 and 100 microgs, respectively, were satisfied with their inductions, and 64% of patients would prefer to have the inducing agent given orally if they were to have another induction.\n Oral misoprostol is effective in inducing labor and seems acceptable to patients. Both the 50 and 100 microgs dose regimens have a reasonable safety profile, but in view of the higher incidence of failed inductions with the 50 microgs dosage, the 100 microgs dose regimen may be the preferred dose regimen.",
"The purpose of this study was to compare orally administered misoprostol with intravenous oxytocin infusion for labor induction in women with favorable cervical examinations (defined as a Bishop score of 6 or more).\n One hundred ninety-eight women with indications for labor induction and favorable cervical examinations were assigned randomly to receive oral misoprostol or oxytocin induction. Misoprostol, 100 mg, was administered every 4 hours up to 6 doses, or intravenous oxytocin was administered by standardized protocol.\n One hundred ten (55.6%) women received misoprostol; 88 (44.4%) received intravenous oxytocin. There was no statistically significant difference in the average interval from start of induction to vaginal delivery, being longer in the misoprostol group (789.4 +/- 510.2 minutes) than in the oxytocin group (654.0 +/- 338.2 minutes, P=.19, log-transformed data). Two women had tachysystole develop in each treatment group. More women in the misoprostol group experienced hyperstimulation (7/110, 6.4%) than in the oxytocin group (0/88, P=.02, Fisher exact test). Nine (8.1%) misoprostol-treated women and 8 (9.1%) oxytocin-treated women underwent cesarean deliveries (P=.82). There was a presumed uterine rupture in a misoprostol-treated multipara women. There were no statistically significant differences in neonatal outcomes between the groups.\n Oral misoprostol offers no benefit over intravenous oxytocin for labor induction in women with favorable cervical examinations. It is associated with a higher likelihood of uterine hyperstimulation and may increase the risk of uterine rupture.",
"To assess the effectiveness and safety of the administration of misoprostol, an orally active prostaglandin, in addition to routine uterotonic therapy as part of the active management of the third stage of labor.\n The present study was a hospital-based, decentralized, multi-center, randomized, placebo-controlled, double-blind trial. We enrolled 1103 women (out of a target sample size of 1180) at 4 hospitals in South Africa, Uganda, and Nigeria. Participants received a sublingual dose of 400 μg of misoprostol or a placebo, in addition to standard active management of the third stage of labor, after vaginal birth.\n The baseline characteristics of the participants were comparable. The difference in the primary outcome of blood loss of 500 mL or more within 1 hour of randomization was not significant between the 2 groups (misoprostol 22/546 [4.0%] versus placebo 35/553 [6.3%]; relative risk, 0.64; 95% confidence interval, 0.38-1.07). Shivering and pyrexia occurred more frequently in the misoprostol group. No maternal deaths occurred.\n The present study did not confirm a beneficial effect of administering 400 μg of misoprostol, in addition to routine uterotonic therapy, during the third stage of labor, but was consistent with other trials showing a cumulative modest benefit. Where routine uterotonics are available for prophylactic use, any potential benefit of misoprostol might not outweigh the likelihood of adverse effects.\n Copyright © 2010 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.",
"The aim of this randomized trial was to compare the efficacy and safety of vaginal misoprostol and oxytocin for cervical ripening and labor induction in patients with premature rupture of membrane (PROM) at term.\n Ninety-seven women with PROM at term were assigned randomly to receive intravaginal misoprostol or oxytocin. The primary outcome measure was the induction-delivery interval. Secondary outcomes included the number of women who delivered vaginally within 12 hours of the start of the induction in the two groups, the cesarean, hyperstimulation, and failed induction rates, the mode of delivery, and the neonatal outcome.\n Forty-eight women were assigned to intravaginal misoprostol and 49 to oxytocin administration. The mean interval from induction to delivery was 10.61 +/- 2.45 hours in the misoprostol group and 11.57 +/- 1.91 hours in the oxytocin group (p = 0.063). The rates of vaginal delivery were 83.3% and 87.7% and cesarean delivery were 16.7% and 8.2% in the misoprostol and oxytocin groups, respectively. Neonatal outcomes were not significantly different. Of the cases, 8.3% in the misoprostol group and 8.2% in the oxytocin group revealed uterine contraction abnormalities.\n Our study demonstrates that, intravaginally, misoprostol results in a similar interval from induction of labor to delivery when compared to oxytocin.",
"To compare the efficacy and complications of intravaginal misoprostol application with oxytocin infusion for induction of labor in great grandmultiparous pregnancies with a Bishop score of <6.\n Sixty-four great grandmultiparous (delivering the tenth, or greater, infant) pregnant patients with a Bishop score of <6 were randomized in two groups with 32 patients receiving 50 microg intravaginal misoprostol four times with 4h intervals, and 32 patients receiving oxytocin infusion for induction of labor starting from 2 mIU/min, increasing it every 30 min with 2 mIU/min increments up to maximum of 40 mIU/min. The time from induction to delivery, the route of delivery, fetal outcome and maternal complications were recorded. Statistical analyses were performed using Mann-Whitney U-test, Chi-Square test and hypothesis test about differences for two proportions (t-test) to determine differences between the two groups. P < or = 0.05 was considered significant.\n The mean time from induction to delivery was 9.91+/-4.30 and 10.88+/-4.72 h in the misoprostol and oxytocin administered group, respectively, with no significant difference between the groups. The rate of vaginal delivery was 84.4 and 87.5% in the misoprostol and oxytocin administered group, respectively, with no significant difference between the groups (P = 0.72). The rates of placental abruption and postpartum hemorrhage were similar in both groups and no case of uterine rupture occurred. The 1 and 5 min mean Apgar scores were 6.91+/-1.57-8.88+/-1.39 and 7.22+/-1.24-9.06+/-0.84 in the misoprostol and oxytocin administered group with no significant differences between the groups (P = 0.38 and 0.51). No case of asphyxia was present. The rate of admission to neonatal intensive care unit was higher in the misoprostol administered group, but the difference was not significant.\n Intravaginal misoprostol is an alternative method to oxytocin in induction of labor in great grandmultiparous pregnant women with low Bishop scores, as it is effective, cheap and easy to use. Safety about rare complications and neonatal morbidity needs clarifications with further studies.",
"To compare effectiveness and safety of 25 microg vaginal misoprostol versus Foley catheter and oxytocin for cervical ripening and labor induction in pregnant women with unripe cervices.\n Randomized controlled trial.\n A public maternity in Recife, Brazil.\n A total of 240 pregnant women.\n Women with a term or post-term, live, singleton fetus in cephalic presentation, intact membranes, Bishop score <6, not in labor, medically indicated for labor induction. They were randomly divided in Group 1, where 119 women received 25 microg of intravaginal misoprostol every 6 hours for a maximum of four doses; and Group 2, where 121 women had a 14-F Foley catheter inserted into their cervical canal. Once past the internal os, the balloon was inflated. Intravenous oxytocin was initiated after the balloon was spontaneously extruded from the cervix or after 24 hours.\n There were no significant differences between the groups regarding baseline characteristics. Misoprostol was more effective in inducing labor than Foley catheter and oxytocin. Mean induction-to-vaginal delivery time with misoprostol was shorter (17.3 vs. 20.2 hours, p = 0.016). There were more vaginal deliveries in the misoprostol group at 12 (p < 0.001) and 18 (p = 0.007) hours, but the difference was no longer statistically significant at 24 and 48 hours. There were no significant differences in uterine contraction abnormalities, puerperal infection or neonatal outcomes.\n Vaginal misoprostol is more effective than and as safe as Foley catheter and oxytocin for induction of labor in term and post-term pregnancy.",
"To compare the efficacy and complications of intravaginal misoprostol application with oxytocin infusion for induction of labor in toxemia of pregnancy with a modified Bishop score of < or =4.\n A hundred preeclamptic women with a modified Bishop score of < or =4 were randomized into two groups of 50 patients one group receiving 50 microg intravaginal misoprostol 4 times at 4 hour intervals, the second group receiving oxytocin infusion for induction of labor starting from 1 mIU/per minute, increasing it every 30 minutes with 2 mIU/per minute increments up to maximum of 30 mIU/per minute. Modified Bishop scores 12 hours after induction, the time from induction to delivery, the route of delivery, fetal outcome and maternal complications were recorded. Statistical analyses were performed using Mann Whitney-U, Chi-Square and hypothesis tests about differences for two proportions (t test) to determine differences between the two groups. p< or =0.05 was considered significant.\n Misoprostol was significantly superior for induction of labor in toxemia of pregnancy with modified Bishop score of < or =4. After 12 hours median modified Bishop scores of misoprostol administered group and oxytocin administered group were 7 and 4 respectively. Misoprostol administered group 1 was significantly better than oxytocin administered group 2 (p=0.027). The rate of patients who were in labor after 12 hours were 94% and 80% in group 1 and 2 respectively and the difference showed significant difference (p<0.05). The median time from induction to delivery was 14 hours and 16 hours in the misoprostol and oxytocin administered group respectively with significant difference between the groups (p=0.003). The rate of vaginal delivery was significantly higher in the misoprostol administered group 1 (82%) when compared with the oxytocin administered group 2 (66%) (p<0.05). The 1 and 5 minutes median Apgar scores were 5-7 and 6-7.5 in group 1 and 2, respectively with no significant differences between the groups (p=0.96, p=0.64). The rate of admission to neonatal intensive care unit was similar in both groups. The complication rates were similar in all groups and no significant detrimental effects were noted.\n Intravaginal misoprostol is an efficacious, cheap and safe method of induction of labor in toxemia of pregnancy with modified Bishop score of < or =4.",
"To compare the safety, efficacy, and costs of intravaginal misoprostol versus dinoprostone vaginal inserts for cervical ripening and labor induction.\n Two hundred twenty-three labor induction patients were assigned randomly to one of two treatment groups: 1) intravaginal misoprostol or 2) dinoprostone vaginal inserts. Fifty micrograms of misoprostol were placed in the posterior vaginal fornix every 3 hours for a maximum period of 24 hours. Ten milligrams of dinoprostone was administered in a single application as a vaginal insert for 12 hours.\n Among 223 patients evaluated, 108 were allocated to the misoprostol group and 115 to the dinoprostone group. The median interval from induction to vaginal delivery was significantly shorter in the misoprostol group: 698 (range 395-1053) versus 1041 (range 792-1531) minutes (P < .001). Vaginal delivery within 12 hours of ripening occurred in 40.7% of patients who received misoprostol compared with 19.1% for those receiving dinoprostone (P < .001); no significant difference between the groups was noted for vaginal delivery within 24 hours. Uterine tachysystole occurred more frequently in patients in the misoprostol group (21.3%) than in the dinoprostone group (7.0%) (P = .004). Nevertheless, no statistically significant differences were noted between the groups with respect to intrapartum complications, including uterine hyperstimulation, mode of delivery, and neonatal or maternal adverse outcomes. The average cost per patient for misoprostol treatment was $85 compared with $606 for treatment with the vaginal insert.\n Intravaginal misoprostol and the dinoprostone vaginal insert appear to be safe agents for cervical ripening and labor induction. However, misoprostol is less expensive and more effective than the dinoprostone vaginal insert.",
"To compare the effectiveness and safety between intravaginal and oral misoprostol for labor induction.\n One hundred and six pregnant women at term with unfavorable cervix (Bishop score < or = 4) and no contraindication to prostaglandin therapy were randomized to receive either intravaginal misoprostol 50 microg every 4 h or oral misoprostol 50 microg every 4 h for prospective randomized controlled trial study. Treatment interval from induction to vaginal delivery, maternal and neonatal complications were the main outcome measures.\n There were no statistical differences of baseline characteristics and Bishop score prior to intervention between both groups. Time interval from induction to vaginal delivery in the oral group was slightly, but significantly, longer than that of the intravaginal group (886.1 +/- 443.5 min vs 637.0 +/- 373.3 min, respectively.) Additionally, the number of doses required was significantly higher in the oral group. Nonetheless, there was no significant difference between both groups with regard to failure of induction and maternal-neonatal complications.\n The effectiveness in terms of failed induction and safety were comparable between intravaginal and oral misoprostol, but intravaginal route was better with respect to treatment interval and number of required doses. Both routes of administration can alternatively be used for labor induction.",
"To determine if oral misoprostol can replace oxytocin for labor stimulation in women with ruptured membranes at term and without evidence of labor.\n Nulliparous women at 36 to 41 weeks with a singleton, cephalic-presenting fetus and ruptured membranes without evidence of labor were randomized to receive oral misoprostol (100 microg) or a placebo every 4 hours for a maximum of two doses. Intravenous oxytocin was initiated if active labor had not ensued within 8 hours of the initial study drug dose.\n Fifty-one women were randomized to oral misoprostol and 51 women to the placebo. Misoprostol reduced the use of oxytocin stimulation of labor from 90% to 37% (P <.001) and was associated with approximately a 7-hour shorter elapsed time in the labor unit. Uterine hyperactivity, defined as six or more contractions in 10 minutes without fetal heart rate decelerations, occurred in 25% of women randomized to misoprostol. However, uterine hyperactivity associated with fetal heart rate decelerations occurred in only three (6%) women, none of whom required emergency cesarean delivery. Route of delivery and infant outcomes were not related to misoprostol use.\n Oral misoprostol (100 microg) given in a maximum of two doses 4 hours apart significantly reduced the use of oxytocin in the management of women with ruptured membranes without labor at term.",
"To compare the efficacy and safety of a 25-microgram vaginal tablet of misoprostol (APL202) with dinoprostone (3-mg vaginal tablet) in cervical ripening and labour induction.\n A randomised, open-label, noninferiority, comparative study in two maternal populations.\n Eighteen NHS study centres across the UK.\n Nulliparous or multiparous women with a singleton pregnancy eligible for induction of labour.\n Women were randomised to receive either misoprostol, initially 25 micrograms (50 micrograms in nulliparous women with Bishop score < or =4) followed by 25 micrograms after 4 and 8 hours, or dinoprostone, initially 3 mg followed by 3 mg after 6 hours. Clinical noninferiority of misoprostol was defined as an absolute difference between treatments of no more than 10% for the primary outcome.\n The number of vaginal deliveries achieved within 24 hours of labour induction. Maternal and fetal safety outcomes.\n A total of 626 women were randomised to misoprostol (n = 318) or dinoprostone (n = 308) treatment. The rate of vaginal deliveries achieved within 24 hours of induction did not significantly differ between the misoprostol and dinoprostone (43 versus 47%; 3.74% difference, 95% CI -3.58 to 11.05, respectively) treatment groups. The treatments were generally comparable for other secondary efficacy measures. Maternal and fetal adverse events were similarly distributed across the misoprostol and dinoprostone groups.\n Low-dose misoprostol is efficacious in cervical ripening and labour induction and demonstrates a similar fetal and maternal safety profile to dinoprostone.",
"Prospective clinical trials were conducted to assess the safety and efficacy of 6-hourly vaginal misoprostol versus intracervical dinoprostone for induction of labor.\n A total of 120 pregnant women requiring induction of labor were recruited. Cases were randomized to receive either 50 microg vaginal misoprostol 6 hourly (group 1, n = 60) or 0.5 mg intracervical dinoprostone 6 hourly (group II, n = 60). Outcome measures, such as change in Bishop's score, need of oxytocin, induction delivery interval; complications like tachysystoly, hyperstimulation, abnormal fetal heart rate, and meconium passage were compared between two groups. Statistical analysis was performed by Wilcoxan's Rank sum and Student's t-test.\n Bishop score rise, after 6 h of initiation of therapy was significantly higher in the misoprostol group than dinoprostone, 2.98 +/- 2.57 versus 2.05 +/- 1.83 (P = 0.04). The need of oxytocin augmentation was reduced in misoprostol versus dinoprostone group, 16.6% versus 78.3% (P = <0.001). Induction delivery interval was shorter in misoprostol; 12.8 +/- 6.4 h versus 18.53 +/- 8.5 h in dinoprostone group (P = <0.01). One case (1.6%) in misoprostol group, but none in dinoprostone had tachystole (P = 1.00). Abnormal heart rate pattern was found more in misoprostol than dinoprostone 16.6% versus 4.9% (P = 0.14) and so was the incidence of cesarean section, 26.6 versus 15%, respectively (P = 0.47). Meconium passage was the same in both groups, 10% in each group.\n Vaginal misoprostol 50 microg 6-hourly is safe and effective for induction of labor with lesser need of oxytocin augmentation and shorter induction delivery interval.",
"Misoprostol is effective for cervical priming prior to vacuum aspiration for first trimester termination of pregnancy. Previous studies showed that the oral route was more acceptable to patients but there were higher incidences of side-effects when compared with the vaginal route. This study is to determine the optimal dosage and route of administration of misoprostol for pre-operative cervical dilatation. A double-blind, randomized trial was undertaken for 225 nulliparous women with 8-12 weeks amenorrhoea. They were randomly assigned to groups given 0 (placebo), 200 or 400 microg oral or vaginal misoprostol 3 h prior to vacuum aspiration. In misoprostol-treated groups the baseline cervical dilatation was significantly increased when compared with the placebo group; the effect was dose-related in the oral but not in the vaginal group. The cumulative force and blood loss was significantly decreased in the misoprostol-treated groups. The incidences of side-effects were more frequent in misoprostol groups but were not related to the route and dosage of medication. The duration of procedure, incidences of post-operative complications, the duration of post-operative bleeding and the interval to the first period were similar in the five treatment groups. We conclude that a 3 h pre-treatment interval is effective for both oral and vaginal routes. When given orally, 400 microg is more effective than 200 microg. The efficacy was otherwise similar when compared with the vaginal route. We recommend 400 microg oral misoprostol 3 h prior to vacuum aspiration for cervical dilatation.",
"To compare the clinical efficacy and side effects of oral misoprostol with vaginal misoprostol for second-trimester pregnancy termination.\n A randomized clinical trial of medical pregnancy termination between 14 and 26 weeks' gestation was conducted. Three misoprostol regimens were compared: 400 microg vaginally at 6-hour intervals (group 1), 400 microg orally at 3-hour intervals (group 2), and a loading dose of 600 microg vaginally followed by 200 microg orally at 3-hour intervals (group 3). A sample size of 225 women was required for equivalence of the three regimens, with an interim safety analysis planned at 80 women.\n A significant difference between the groups was evident at the interim safety analysis and the study ceased. The subset of 84 women recruited before the study closure is described. There was a significant difference in the median time to achieve delivery among the three groups: group 1, 14.5 hours (95% confidence interval 12.0, 16.9), versus group 2, 25.5 hours (13.5, 23.8), versus group 3, 16.4 hours (interquartile range 14.2-37.3) (P =.042). Within 24 hours of commencement 85.7% of women in group 1, 44.8% in group 2, and 74.1% in group 3 delivered (P =.003). At 48 hours 0% in group 1, 20.7% in group 2, and 3.7% in group 3 were undelivered (P =.011). There was no difference in women's perceptions of the termination process.\n In second-trimester pregnancy termination, a vaginal misoprostol regimen of 400 microg every 6 hours was 1.9 times more likely to result in delivery within 24 hours from commencement than an oral regimen of 400 microg every 3 hours.",
"A randomised prospective trial was carried out to compare the efficacy and safety of intravaginal Misoprostol with intracervical dinoprostone gel for induction of labour in cases of unfavourable cervix. One hundred women with an unfavourable cervix requiring induction of labour were randomised to receive either 25 microm vaginal Misoprostol 4-hourly or 0.5 mg of intracervical dinoprostone 12 hourly. The outcome measured was change in Bishop's score, percentage of women going into labour, induction to delivery interval, need for oxytocin, mode of delivery and complications. The parity, mean period of gestation and Bishop's score were similar in both the groups. The improvement in Bishop's score at 12 h was significantly better in the Misoprostol group. Induction to delivery interval was shorter in the Misoprostol group, 16.59 +/- 5.13 h vs 27.77 +/- 12.71 h. The rate of complications was comparable. Vaginal Misoprostol 25 microg 4-hourly is safe and effective for induction of labour with shorter induction to delivery interval.",
"Our purpose was to compare the efficacy 25 micrograms and 50 micrograms dosage of intravaginal misoprostol for labor induction in patients with an unfavorable cervix. Fifty pregnant women were randomly assigned to receive either 25 micrograms (24 cases) or 50 micrograms (26 cases) of intravaginal misoprostol every 6 hours. The mean interval from induction to vaginal delivery was significantly shorter in the 50 micrograms group (13.8 +/- 6.6 hours) when compared with the 25 micrograms group (20.9 +/- 9.5 hours) (P = 004). The average number of misoprostol doses needed per patient was significantly fewer in the 50 micrograms group (1.6 +/- 0.7 versus 2.3 +/- 1.2, P = 0.018). The frequencies of uterine tachysystole were 4.2 per cent and 7.7 per cent in the 25 micrograms and 50 micrograms groups respectively which did not significantly differ. Requirement for oxytocin infusion in the 25 micrograms group was significantly more than in the 50 micrograms group (66.6% versus 23.1% respectively, P = 0.004). Analgesia requirement, delivery method, and perinatal outcomes were comparable in both groups. In summary, intravaginal application of 50 micrograms misoprostol at 6-hour interval is comparable in safety but more effective for labor induction than the 25 micrograms dosage.",
"Misoprostol, a synthetic E1 methyl analog prostaglandin, is at present receiving attention as a cervical modifier and labor induction agent. However, there is still a need for better determination of its safety and effectiveness.\n To compare intravaginal misoprostol versus intravenous oxytocin for cervical ripening and labor induction in pregnant women with unripe cervices.\n Randomized controlled trial.\n The study was performed at the Leonor Mendes de Barros Maternity Hospital between November 1998 and December 2000.\n 210 pregnant women with intact membranes and indication for labor induction were selected.\n The women randomly received 25 g of vaginal misoprostol every 4 hours, not exceeding 8 doses (105 women), or oxytocin in a continuous infusion (105 women).\n The main parameters measured were: latent period, time from induction to vaginal delivery, delivery route, occurrence of vaginal delivery with time, occurrence of uterine tonus alterations, hypoxia and neonatal morbidity. To verify the statistical significance of the differences between the groups, the chi-squared, Student t and log-rank tests were used.\n There were no significant differences between the groups concerning conditions for labor induction, age, parity, race, marital status, family income, initial Bishop Index and number of prenatal visits. The cesarean section rate, latent period and period from induction to vaginal delivery were significantly lower for the misoprostol group. With regard to uterine tonus alterations, tachysystole was significantly more common in the misoprostol group. However, there was no difference in hypoxia and neonatal morbidity between the groups.\n 25 g of misoprostol used vaginally every 4 hours is safer and more efficient for cervical ripening and labor induction than oxytocin.",
"To evaluate the efficacy and safety of oral misoprostol for labor induction in women with term premature rupture of membranes (PROM) and an unfavorable cervix.\n We randomized 130 women with PROM of < or =4 h to either oral misoprostol, 50 microg, or a placebo given every 4 h for up to three doses. Intravenous oxytocin was initiated if active labor did not begin within 12 h.\n Sixty-four women received oral misoprostol and 66 received placebo. The PROM-to-delivery interval was shorter with misoprostol than with placebo (13.7+/-5.8 vs. 20.3+/-6.8 h, respectively, P<0.05). Misoprostol significantly reduced the need for oxytocin (28.1 vs. 72.7%, P<0.001) and antibiotics (25 vs. 69.7%, P<0.001). No significant differences in cesarean section or hyperstimulation rate were noted.\n Oral misoprostol given to women with unfavorable cervix soon after term PROM significantly reduces the induction-to-delivery time and the need for oxytocin and antibiotics.",
"To compare the efficacy of two different dosages of oral misoprostol (50 and 100 microg) with control, in medical induction of labor for patients with prelabor rupture of membranes (PROM) at term.\n One hundred women with PROM at term were randomized to receive placebo (vitamin B6 50 mg, control), 50 microg (treatment group 1), or 100 microg (treatment group 2) of oral misoprostol every 4 h to a maximum of six doses. The main outcome measures included time interval from onset of PROM to delivery, duration of first stage of labor, and occurrence of vaginal delivery within 24 h from PROM.\n The time intervals from PROM to delivery were significantly reduced in both treatment groups compared to control (control, 25.1+/-10.5 h; treatment group 1, 14.5+/-6.2 h; and treatment group 2, 13.0+/-6.1 h, p<0.0001 for both). The duration of the first stage of labor was significantly shortened only in treatment group 2 compared to control (3.3+/-2.5 versus 6.2+/-3.4 h, p=0.01). Of those who delivered vaginally (93% in treatment group 1 and 97% in treatment group 2), significantly more women delivered within 24 h of PROM in the treatment group compared to the control group (50%, p<0.05).\n Oral misoprostol 50 microg every 4 h is safe, cheap, and as effective as 100 microg in reducing the PROM to delivery time interval and labor duration in primiparous women. The same effect is not observed in a multiparous group.",
"Our purpose was to compare the efficacy and safety of misoprostol with dinoprostone (Prepidil) for labor induction.\n In a randomized, controlled trial of labor induction, patients were randomly assigned to receive either 50 microgram of intravaginal misoprostol every 4 hours or 0.5 mg of intracervical prostaglandin E2 every 6 hours. Eligibility criteria included gestation of >/=31 weeks, Bishop score <6, and fewer than 12 contractions per hour. Primary outcomes were cesarean section, induction to delivery time, oxytocin use, and fetal distress requiring delivery.\n One hundred fifty-nine women were randomly assigned to receive misoprostol (n = 81) or Prepidil (n = 78). There were no differences in the indication for induction, preinduction Bishop score, epidural use, or cesarean section rate. Mean time to delivery was significantly shorter in the misoprostol group (19 hours 50 minutes) than in the Prepidil group (28 hours 52 minutes) (P =.005). Only 58% of women in the misoprostol group required oxytocin augmentation, in comparison with 88% of women receiving Prepidil (P =.00002). However, 41% of women receiving misoprostol and 17% receiving Prepidil had late decelerations or bradycardias (P =.001), and 20% of the misoprostol group and 5% of the Prepidil group had deliveries for fetal distress (P =.05).\n Misoprostol is more efficacious than Prepidil for labor induction. However, the significantly increased incidence of abnormal fetal heart rate tracings and the trend in increased deliveries for fetal distress with misoprostol dosing of 50 microgram every 4 hours are of concern. These data suggest that either a lower dose of misoprostol or less frequent dosing of misoprostol should be considered.",
"To determine the optimal evacuation time interval in the use of vaginal misoprostol for cervical priming before first trimester termination of pregnancy.\n Prospective double-blind randomised study.\n Fertility Control Centre, National University Hospital, Singapore.\n Sixty healthy nulliparous women requesting legal termination of pregnancy between 6 and 11 weeks of gestation were randomly allocated to either the 400 microg or 600 microg misoprostol group. Vacuum aspiration was performed after three hours in the 400 microg group and at the end of two hours in the women given 600 microg misoprostol. Using Hegar's dilator, degree of cervical dilatation before operation was measured. Other parameters assessed included the amount of additional dilatation required (if < Hegar 8), pre-operative and intra-operative blood loss, and associated side effects.\n For the 600 microg group, only five women (16.7%) achieved a cervical dilatation of > or = 8 mm, compared with 28 women (93.3%) in the 400 microg group. Using the 400 microg misoprostol group as a baseline, the odds ratio was 0.014 (95% CI 0.003-0.080) for 600 microg for successful pre-operative cervical dilatation of > or = 8 mm. The mean cervical dilatation for 400 and 600 microg misoprostol was 8.1 mm and 6.6 mm, respectively (P < 0.001). Despite the shorter evacuation time interval of two hours, the 600 microg dose was associated with an increase in side effects such as vaginal bleeding, abdominal pain and a fever of > 38.0 degrees C. However, other than abdominal pain, no significant differences in the frequency of these side effects were shown.\n Use of 400 microg misoprostol with a minimal evacuation time interval of three hours still appears the optimal dosage and evacuation time for cervical priming before first trimester termination of pregnancy.",
"To compare intravaginal misoprostol to prostaglandin (PG) E2 for cervical ripening in women with premature rupture of the membranes (PROM) after 34 weeks of gestation.\n Women with PROM after 34 weeks of gestation and an unripe cervix were randomized to receive PGE2 (2.5 mg) or misoprostol (50 microg). Both agents were placed intravaginally immediately after randomization, and the dose was repeated 6 hours later if necessary. After another 6 hours from the second insertion, oxytocin treatment was started if labor had not begun. Forty patients in each group were required to show a 30% improvement in delivery within 12 hours in the misoprostol group.\n One hundred nine patients were randomized; 54 were assigned to misoprostol and 55 to PGE2. Important demographic and clinical characteristics were similar between the groups. The mean time from first insertion to delivery was 16.4 hours in the misoprostol group and 22.0 hours in the PGE2 group. A second dose was required less frequently in the misoprostol group (22% vs 62% in the PGE2 group), and the percentage of patients delivered within 12 hours was higher in the misoprostol group (41% vs 16%). Tachysystole occurred in 20% and 6% of women in the misoprostol and PGE2 groups, respectively. Hyperstimulation occurred in 9% and 0%, and cesarean delivery in 19% and 26% of women in the misoprostol and PGE2 groups, respectively. Neonatal outcome was similar between groups.\n Intravaginal misoprostol is more effective than local PGE2 application to treat PROM after 34 weeks of gestation, but tachysystole occurs more commonly with misoprostol.",
"To evaluate the induction-to-abortion time of 3 pharmacokinetic-based protocols at 13-20 weeks of gestation.\n A randomized trial was conducted on 153 patients. The oral group (n = 51) received 100 microg misoprostol orally every 2 hours, the vaginal group (n = 51) received 200 microg misoprostol vaginally every 4 hours, and the sublingual group (n = 51) received 100 microg misoprostol sublingually every 2 hours.\n The mean induction-to-delivery time was shorter in the sublingual group (mean, 651 +/- 507) as compared to the vaginal group (mean, 1,056 +/- 634, p = 0.01). The number of patients who delivered within 12 hours was significantly higher in the sublingual group (n = 39, 78%) as compared to the oral (n = 26, 52%) and vaginal (n = 20, 40%) groups (p < 0.001). The numbers of patients who delivered within 24 hours were comparable in the sublingual (n = 47, 94%) and oral (n = 46, 92%) groups but higher than in the vaginal group (n = 39, 78%; p = 0.02). The total misoprostol dose was 543 +/- 422 microg in the sublingual group, 878 +/- 533 microg in the vaginal group and 741 +/- 413 microg in the oral group (p < 0.001).\n A pharmacokinetic-based application of 100 microg of sublingual misoprostol every 4 hours is more effective for induction of second-trimester abortion as compared to 100 microg oral misoprostol every 2 hours and 200 microg vaginal misoprostol every 4 hours.",
"A prospective randomised controlled trial was performed to compare the efficacy and safety of intravaginal misoprostol to that of intravaginal dinoprostone when used for cervical priming prior to the induction of labour; 126 women were recruited to the study and randomised to receive either intravaginal dinoprostone (n = 63) or misoprostol (n = 63) for cervical priming prior to induction of labour. The mean time from insertion of the priming agent to vaginal delivery was significantly shorter in the misoprostol group (925.8 versus 1577.6 minutes), the mean duration of the active length of labour was significantly shorter in the misoprostol group (353.7 versus 496.8 minutes) and more women in the misoprostol group delivered in less than 12 hours (92% versus 76.5%). Women in the misoprostol group were less likely to require a repeated dose of prostaglandin for cervical priming and less likely to require oxytocin for augmentation of labour. There was no difference in the number of women who were delivered vaginally or by Ceasarean section between the two groups. More women developed hyperstimulation during labour in the misoprostol group; however there was no difference between the groups in neonatal outcome in respect to low cord pH or Apgar score at delivery or admission to the neonatal special care nursery.",
"The objective of this randomized prospective study was to compare the efficacy of 50 mcg vaginal misoprostol and 3 mg dinoprostone, administered every nine hours for a maximum of three doses, for elective induction of labor in a specific cohort of nulliparous women with an unfavorable cervix and more than 40 weeks of gestation.\n One hundred and sixty-three pregnant women with more than 285 days of gestation were recruited and analyzed. The main outcome measures were time from induction to delivery and incidence of vaginal delivery within 12 and 24 hours. Admission rate to the neonatal intensive care unit within 24 hours post delivery was a secondary outcome.\n The induction-delivery interval was significantly lower in the misoprostol group than in the dinoprostone group (11.9 h vs. 15.5 h, p < 0.001). With misoprostol, more women delivered within 12 hours (57.5% vs. 32.5%, p < 0.01) and 24 hours (98.7% vs. 91.4%, p < 0.05), spontaneous rupture of the membranes occurred more frequently (38.8% vs. 20.5%, p < 0.05), there was less need for oxytocin augmentation (65.8% vs. 81.5%, p < 0.05) and fewer additional doses were required (7.5% vs. 22%, p < 0.05). Although not statistically significant, a lower Caesarean section (CS) rate was observed with misoprostol (7.5% vs. 13.3%, p > 0.05) but with the disadvantage of higher abnormal fetal heart rate (FHR) tracings (22.5% vs. 12%, p > 0.05). From the misoprostol group more neonates were admitted to the intensive neonatal unit, than from the dinoprostone group (13.5% vs. 4.8%, p > 0.05). One woman had an unexplained stillbirth following the administration of one dose of dinoprostone.\n Vaginal misoprostol, compared with dinoprostone in the regimens used, is more effective in elective inductions of labor beyond 40 weeks of gestation. Nevertheless, this is at the expense of more abnormal FHR tracings and more admissions to the neonatal unit, indicating that the faster approach is not necessarily the better approach to childbirth.",
"To compare the labour pattern and uterine activity of oral misoprostol with oxytocin for labour induction in women presenting with prelabour rupture of membranes at term.\n Prospective randomised study.\n Department of Obstetrics and Gynaecology, Queen Mary Hospital, Hong Kong.\n Eighty women presenting with prelabour rupture of membranes at term.\n The women were randomised to receive either 100 microg misoprostol orally every 4 hours to a maximum of three doses, or intravenous oxytocin infusion according to the hospital protocol. Intrauterine pressure transducers were inserted one hour before induction of labour in both groups of women. We compared the pattern of uterine activity, the induction-to-delivery interval, duration of labour, mode of delivery and neonatal outcome between the two groups.\n Both oxytocin and oral misoprostol caused an increase in uterine activity within one hour of labour induction. Peak uterine activity was reached 6-8 h after oral misoprostol, with persistent effects, and 8-10 h after oxytocin, requiring continuous titration of medication. The duration of labour was significantly reduced in nulliparous women, but not in those who were multiparous in the misoprostol group. The induction-to-delivery interval, the mode of delivery and the perinatal outcome were similar for the two groups.\n Oral misoprostol caused earlier peak uterine activity, compared with oxytocin (6-8 h vs 8-10 h). Oral misoprostol was not only as effective as oxytocin in inducing labour in women at term with prelabour rupture of the membranes, but it reduced significantly the duration of labour in nulliparous women.",
"We compared labor induced by vaginal misoprostol versus a supracervical Foley catheter and oral misoprostol. Singleton pregnancies at > or = 24 weeks' gestation were randomized to either an initial 25-microg dose of intravaginal misoprostol, followed by 50-microg intravaginal doses at 3- to 6-hour intervals, or a supracervical Foley balloon and 100 microg of oral misoprostol at 4- to 6-hour intervals. Primary outcome was time from induction to delivery. One hundred twenty-six women were randomized to vaginal misoprostol alone (group I) and 106 women to Foley and oral misoprostol (group II). The groups were similar in age, weight, gestational age, parity, indication for induction of labor, and oxytocin use. Cesarean delivery rates at 37% and cesarean indications were similar ( P = 0.25). The time from induction to delivery in group II (12.9 hours) was significantly shorter than that in group I (17.8 hours, P < 0.001). Uterine tachysystole occurred less often in the vaginal misoprostol group (21% versus 39%, P = 0.015). Compared with vaginal misoprostol, delivery within 24 hours was significantly more likely with a Foley balloon and oral misoprostol. The use of terbutaline and peripartum outcomes were similar in the two groups.",
"This study was undertaken to determine whether induction of labor with oral misoprostol will result in fewer cesarean deliveries than intravenous oxytocin in nulliparous women with premature rupture of membranes at term.\n Three hundred five women at 10 centers were randomly assigned to receive oral misoprostol, 100 microg every 6 hours to a maximum of two doses or intravenous oxytocin. The primary outcome measure was cesarean deliveries. Secondary outcomes were time from induction to vaginal delivery and measures of maternal and neonatal safety.\n The study was stopped prematurely because of recruitment difficulties. We present the results for the 305 enrolled women. There was no difference in the proportion of women who underwent cesarean delivery (20.1% in the misoprostol group, 19.9% in the oxytocin group). The time interval from induction to vaginal delivery was also similar (11.9 hours for the misoprostol group, and 11.8 hours for the oxytocin group). Maternal and neonatal safety outcomes were similar for the two treatments. More infants born to women in the misoprostol group received intravenous antibiotics in the neonatal period (16.4% vs 6.9%, P=.01), although there were no differences in chorioamnionitis or in proven neonatal infections. Women receiving misoprostol were less likely to have postpartum hemorrhage than those receiving oxytocin (1.9% vs 6.2%, P=.05).\n Oral misoprostol does not offer any advantage in time from induction to vaginal delivery or risk of cesarean section.",
"To compare vaginal misoprostol with dinoprostone for induction of labour.\n Randomised multicentre trial.\n Labour wards of one university hospital and two teaching hospitals.\n Six hundred and eighty-one women with indication for labour induction at >or=36 weeks of gestation, singleton pregnancy and no previous ceasarean section.\n Misoprostol (25 mcg, hospital-prepared capsule) in the posterior vaginal fornix, every four hours, maximum three times daily or dinoprostone gel (1 mg) every four hours. Oxytocin was administered if necessary.\n Primary: 'adverse neonatal outcome' (5-minute Apgar score <7 and/or umbilical cord pH <7.15). Secondary: labour duration, mode of delivery and patient satisfaction.\n Three hundred and forty-one women received misoprostol and 340 dinoprostone. The median induction-delivery interval was longer in the misoprostol group compared with the dinoprostone group (25 versus 19 hours, P= 0.008). The caesarean section rate was lower in the misoprostol group: 16.1%versus 21%, but this difference was not statistically significant RR = 0.8 (95% CI 0.6-1.04). 'Adverse neonatal outcome' was found to be similar in both groups: 21% in the misoprostol and 23% in the dinoprostone groups. Significantly fewer neonates were admitted to NICU in the misoprostol group compared with dinoprostone 19%versus 26% (RR = 0.7, 95% CI 0.5-0.98).\n Misoprostol in this dosing regimen is a safe method of labour induction. NICU admission rates were lower in the misoprostol group. No difference could be detected in patient satisfaction between groups.",
"The objective of the study was to compare the effectiveness, safety, and side effects of low-dose oral misoprostol with vaginal dinoprostone for cervical ripening and labor induction.\n Women with Bishop score 6 or less admitted for labor induction at term were eligible for this randomized controlled trial. Exclusion criteria were multiple pregnancy, breech, fetal distress, or previous uterine scar. The allocation to the oral misoprostol group (20 microg given every 2 hours increased to 40 microg depending on uterine contractions) or to the vaginal dinoprostone group (2 mg twice, 6 hours apart) was contained in a sealed, opaque, and consecutively numbered envelope.\n Two hundred women (100 in each group) were included. The proportion of vaginal delivery within 24 hours was 56% in the misoprostol group and 62% in the dinoprostone group (relative risk 0.90, 95% CI 0.72-1.14). The risk of cesarean section was 18% and 19%, respectively. The median interval to delivery, calculated from survival analysis, was longer in the misoprostol group (1305 minutes) compared with the dinoprostone group (1080 minutes). The log-rank test was not significant (P =.35). Uterine hyperstimulation occurred in 9% of women in the misoprostol group compared with 14% in the dinoprostone group (P =.27). The only significant difference in neonatal outcomes was a more frequent presence of thick meconium in the misoprostol group (P =.03).\n We found no difference in terms of effectiveness and safety between low-dose oral misoprostol and vaginal dinoprostone used for induction of labor. This regimen avoids the excessive uterine contractility noted in previous studies, where higher doses of misoprostol were administered at longer intervals.",
"To compare the impact of 400 mug oral versus self-administered vaginal misoprostol at home on pre-operative cervical priming in both primigravid and multigravid women prior to first trimester surgical abortion.\n Randomised controlled trial.\n Norwegian University Teaching Hospital.\n Three hundred and thirty-eight women undergoing surgical abortion between 7 and 12 weeks of gestation.\n The women were randomised to either 400 microg of oral misoprostol the evening before or 400-microg of self-administered vaginal misoprostol at home the same day as vacuum aspiration. Main outcome measures Pre-operative cervical dilatation, complications and acceptability.\n The median cervical dilatation was 6.2 mm (range 0-11 mm) for the women in the 400 mug oral misoprostol and 6.5 mm (range 0-11 mm) in the 400-microg vaginal misoprostol groups. The median pre-operative dilatation was larger in multigravidae (6.4 and 6.7 mm for the oral and vaginal routes, respectively) than in primigravidae (5.8 and 6.0 mm, respectively). In primigravidae, 19% achieved a pre-operative dilatation of > or = 7 mm, with no significant difference between oral and vaginal dosage. In multigravidae, 52% achieved a pre-operative dilatation of > or = 7 mm with vaginal dosage, compared with 36% with oral dosage (P = 0.03). There was no difference between non-immigrant versus immigrant women in pre-operative cervical dilatation. The 400-microg oral dosage group had a higher risk of bleeding, compared with the group receiving 400-microg vaginal misoprostol [odds ratio (OR) = 10.4; confidence interval (CI) 5.2-20.8]. There was no difference between non-immigrant and immigrant women in acceptability of self-administered vaginal misoprostol; almost all women found this administration route acceptable. Complications were minor and were distributed equally between the two dosage groups.\n The vaginal route will result in a satisfactory dilatation in about half of multigravidae but is much less effective in primigravidae. The oral route does not lead to satisfactory dilatation in either group and is associated with a higher occurrence of pre-operative bleeding. Self-administered vaginal misoprostol at home is highly acceptable.",
"To evaluate the efficacy of oral and vaginal misoprostol compared with the standard regimen using dinoprostone for induction of labor.\n We conducted a multicenter, randomized controlled trial in Cape Town, South Africa. A total of 573 women admitted for induction of labor were randomized to receive oral misoprostol, vaginal misoprostol, or the control, dinoprostone. Misoprostol was given orally or vaginally as a 50-microg dose at 6-hour intervals to a maximum of four doses. The dinoprostone gel was given as a 1-mg dose in the posterior fornix every 6 hours (maximum two doses).\n There was no significant difference in vaginal delivery rate in 24 hours between the vaginal misoprostol and dinoprostone groups. However, significantly fewer women delivered vaginally in the oral misoprostol group compared with those in the dinoprostone group (relative risk 0.71, 99% confidence interval 0.51, 0.99). The median induction to vaginal delivery time in the vaginal misoprostol, oral misoprostol, and dinoprostone groups was 12 hours, 23 hours, and 14 hours, respectively. The cesarean rate was approximately 33% in all the groups. There were more cesareans performed for fetal distress in the vaginal misoprostol group compared with the dinoprostone group (relative risk 2.86, 99% confidence interval 1.49, 5.46). There was a higher incidence of tachysystole in the vaginal misoprostol group (5.8%) compared with the other two groups: oral misoprostol (0.8%) and dinoprostone (0.8%), but this difference was not statistically significant. There were no differences in maternal or fetal complications.\n Vaginal misoprostol is as effective as dinoprostone in induction of labor, but it is associated with more tachysystole and cesarean sections for fetal distress compared with dinoprostone. Oral misoprostol results in fewer vaginal deliveries in 24 hours, but it is not associated with increased tachysystole or fetal distress.",
"Mifepristone was recently approved in the United States. Regimens with shorter intervals may be more acceptable. The objective of this study was to determine whether the oral route of misoprostol was as effective as the vaginal route of misoprostol 1 day after mifepristone. A prospective, open-labeled, randomized trial of healthy adult women up to 63 days pregnant and wanting a medical abortion were randomized to use either two doses of oral misoprostol 400 microg taken 2 h apart or misoprostol 800 microg vaginally. Women self-administered misoprostol 1 day after taking one-third of the standard dose of mifepristone (200 mg) orally. Women then returned to the clinic up to 5 days later for a repeat sonogram evaluation. A dose of vaginal misoprostol was administered to women with a continuing pregnancy who then returned 1 day later to Day 15. The primary outcome measures were a complete medical abortion by the first or by the second follow-up visits. Surgical intervention was indicated for continuing pregnancy at the second follow-up visit, excessive bleeding, or persistent products of conception 5 weeks later. One thousand one hundred sixty-eight women were enrolled. Of the 1144 (98%) women who complied with their random assignment, two oral doses of misoprostol (800 microg total) were 90% effective at inducing an abortion by the first follow-up visit, compared with one dose of misoprostol by vagina of 97% (chi(2) = 23.95, p = 0.001). By the second follow-up visit, the complete abortion rate was 95% for oral misoprostol and 99% for vaginal misoprostol (chi(2) = 21.76, p = 0.001). There were minimal differences in side effects. Women preferred the oral route. The trial demonstrated that although two doses of oral misoprostol were effective, the vaginal misoprostol was more effective at inducing an early medical abortion at 1 day after low-dose mifepristone, and the regimen could be extended to 63 days gestation.",
"To compare the effectiveness of vaginal misoprostol administered 6 or 12 hourly for second trimester pregnancy termination.\n A randomised controlled trial.\n University teaching hospital.\n Two hundred and seventy-nine pregnant women at gestations between 14 and 26 weeks undergoing pregnancy termination.\n Women were randomised to receive 600-microg misoprostol tablets vaginally either every 6 hours or every 12 hours until abortion occurred.\n Induction-abortion interval, success rate within 24 and 48 hours and adverse effects.\n There was no significant difference in the median induction to abortion interval 6 hours (16 hours) and 12 hours (16 hours; P= 0.80). The total dose of misoprostol was higher in the 6-hour group (1800 vs 1200 microg). The cumulative abortion rates within 24 hours were 74% and 67% and within 48 hours 94% and 92%, in the 6- and 12-hour groups, respectively. Fever was more common in the 6-hour group (53%) versus the 12-hour group (31%; P < 0.001). The incidence of nausea, vomiting, diarrhoea, severe bleeding and abdominal pain were similar.\n Misoprostol (600 microg) administered at 12-hour intervals was associated with fewer adverse effects and was as effective as a 6-hour interval.",
"To determine the efficacy of 200 microg single dose oral misoprostol as a cervical priming agent at term.\n In this double-blind randomized trial, 156 pregnant women requiring induction of labor with gestational age of 37-42 weeks and Bishop score < or =5, were randomized to receive either 200 microg of misoprostol or a placebo, orally. Labor was induced with intravenous oxytocin infusion 12 h after oral medication if the patient did not go into labor. The primary outcome was the change in the Bishop score 12 h after oral medication. The secondary outcomes were the timings starting from the drug administration to the onset of uterine activity, interval between oral medication and delivery, oxytocin need for induction, mode of delivery, frequency of side effects, and neonatal and maternal outcome. The chi-square or Fisher exact test, Student's t-test, and Mann-Whitney U-test were used for analysis of the data.\n There were no significant differences in maternal characteristics or indications of induction. The Bishop score 12 h after oral medication significantly improved in the misoprostol group compared with the control group [55 (70%)>8 vs. 4 (5%)>8; P<0.001]. The induction rate was significantly reduced in the misoprostol group (P<0.001). The interval between oral medication and the onset of uterine activity was significantly shorter in the misoprostol group (P<0.001). The interval between oral medication and delivery was also significantly shorter in the misoprostol group (P<0.001). The cesarean delivery rate was significantly lower in the misoprostol group (P<0.001). There were no differences between the groups with respect to the incidence of tachysystole, hyperstimulation, adverse neonatal or maternal outcome.\n Oral administration of 200 microg single dose of misoprostol is an effective agent not only for cervical priming but also for induction of labor at term. Furthermore, it reduces the rate of cesarean deliveries.",
"A prospective study was carried out at a tertiary care hospital on 100 pregnant women admitted for induction of labour to compare the effect of misoprostol and dinoprostone on the induction of labour. The patients were divided randomly into two groups of 50 each. Group I received 25 microg misoprostol intravaginally every 3 h (maximum dose 200 microg), and Group II received 0.5 mg PGE(2) gel (dinoprostonev) intracervically every 6 h (maximum three doses in 24 h) until good uterine contractions started. The primary outcome measure was vaginal delivery occurring within 24 h of administration of the first dose of either study drug (successful induction). Statistical analysis were conducted using chi(2) test, Fisher exact test, Student's t-test and relative risk (RR) with 95% confidence interval (CI). In the misoprostol group, more patients achieved successful inductions as compared with the dinoprostone group, 80% vs. 62% (P = 0.0473, RR 1.63, 95% CI 0.95-2.81). The mean induction to delivery interval (IDI) was shorter in the misoprostol group, 13.30+/-8.74 (3-40.15) hours, as compared with the dinoprostone group, 18.53+/-11.33 (2-48.07) hours (P = 0.011). Misoprostol was associated with significantly less oxytocin use (18% vs. 50%) as compared with dinoprostone (P = 0.001 RR 0.36, 95% CI 0.19-0.69). In conclusion, although both misoprostol and dinoprostone appear to be effective agents for labour induction, misoprostol is cheaper, stable at room temperature, has shorter IDI and requires less oxytocin. These results make misoprostol superior to dinoprostone for induction of labour especially in developing and tropical countries.",
"Misoprostol is being used increasingly in clinical practice for cervical ripening in first-trimester abortions, but because of lack of good evidence of its effectiveness, administration consensus has not been reached on dosage, route of administration, time of administration pre-operatively and gestational age group. In this study we tested the hypothesis that self-administration of 600 micrograms vaginal misoprostol is feasible and when used 2-4 hours pre-operatively results in sufficient cervical dilatation to make suction curettage easier.\n A double-blind, randomised, placebo-controlled trial was undertaken. Two hundred and seventy-eight women scheduled for termination of pregnancy of up to 12 weeks' duration by manual vacuum aspiration were assigned to receive either 600 micrograms misoprostol pre-operatively, or placebo. The achievement of 'satisfactory' (> or = 7 mm) baseline cervical dilatation after 2-4 hours was evaluated as the primary outcome. Secondary outcome measurements included ease and duration of the procedure. Side-effects such as pre-operative bleeding, gastro-intestinal complaints and pain as well as adverse events were noted in all cases.\n Self-administration of vaginal misoprostol was successful in all women and 273 women were evaluated for main end-points. A significantly larger proportion of patients in the treatment group reached cervical dilatation of > or = 7 mm (67.3% v. 30.9%, P < 0.0001). The side-effects were minimal and comparable in the two groups. In the treatment group the mean procedure duration was significantly shorter (220 seconds v. 321 seconds, P = 0.0013) and the procedure was more likely to be rated by the operator as 'easy' (81.8% v. 63.3%, P = 0.0082). This resulted in a significant reduction in treatment failure in the < 70-day gestation group (5.0% v. 14.7%, P = 0.005).\n It is feasible, safe and effective for 600 micrograms misoprostol to be self-administered vaginally 2-4 hours pre-operatively for cervical priming prior to manual vacuum aspiration. Further research is needed to establish optimal use in the first trimester and to determine patient acceptance.",
"To compare efficacy, safety, and tolerance of oral misoprostol with intracervical dinoprostone for cervical ripening and labor induction.\n Two hundred women were randomized to receive single doses of oral misoprostol 200 microg or 0.5 mg of dinoprostone intracervically every 6 hours for a maximum four doses.\n The intervals from administration of the drug to active phase of labor (11.1 hours [7-24] versus 15.8 hours [7.5-29.62], P =. 01), to delivery (14.0 hours [8.42-27.61] versus 20.2 hours [16.7-32. 8], P =.01), and to rupture of membranes (10.0 hours [4.95-24.7] versus 15.6 hours [8.2-29.2], P =.003) were significantly shorter in the misoprostol group. All those variables were not distributed normally, so results are presented as median and interquartile range. The rates of women who needed oxytocin (68% versus 52%, P =.03) and cesarean for failed induction (9% versus 1%, P =.01) were higher in the dinoprostone group.\n A single dose of 200 microg oral misoprostol was more effective for cervical ripening and labor induction than 0.5 mg of dinoprostone intracervically every 6 hours, with a maximum of four doses.",
"To compare the efficacy of vaginal with oral misoprostol in termination of second-trimester pregnancy after pretreatment with mifepristone.\n Women requesting termination of second-trimester pregnancy were randomized into two groups. Thirty-six to 48 hours after oral administration of 200 mg of mifepristone, women were given either oral or vaginal misoprostol 200 microg every 3 hours for a maximum of five doses in the first 24 hours. Women receiving oral misoprostol also were given a vaginal placebo (vitamin B6), whereas those receiving vaginal misoprostol were given an oral placebo. If they failed to abort, a second course was given by the same route.\n The median induction-abortion interval in the vaginal group (9 hours) was significantly shorter than that in the oral group (13 hours). The percentage of women aborting within 24 hours in the vaginal group (90%) was significantly higher than that in the oral group (69%). The median amount of misoprostol used in the vaginal group (600 microg) also was significantly less than that in the oral group (1000 microg). There was no significant difference in the incidence of side effects between the two groups except for fatigue and breast tenderness, which were more common in the oral group. Seventy-six percent of the women preferred the oral route, and 24.5% of the women preferred the vaginal route.\n Vaginal misoprostol is more effective than oral misoprostol in termination of second-trimester pregnancy after pretreatment with mifepristone, but more women preferred the oral route.",
"To compare the efficacy and safety of two prostaglandin derivatives, misoprostol and dinoprostone, for ripening the cervix and inducing labor in women with an unfavorable cervix.\n One hundred fifty-five women admitted for induction of labor to St. John's Mercy Medical Center, a teaching community hospital, were randomized to one of two methods: intravaginal misoprostol, 50 microg every 4 hours up to three doses (n = 76); and intracervical dinoprostone gel, 0.5 mg every 6 hours up to three doses (n = 79).\n Misoprostol was more effective than dinoprostone in causing cervical ripening (P = .01), inducing labor (P < .001), shortening the duration of labor (P < .001), and decreasing the need for oxytocin augmentation (P < .001). Nonreassuring fetal heart monitoring patterns associated with hyperstimulation were significantly more frequent (P < .001), and the incidence of cesarean deliveries because of this indication was significantly higher (P = .002) in patients receiving misoprostol.\n Misoprostol is an effective agent for cervical ripening and labor induction, but it causes an increase in cesarean deliveries associated with uterine hyperstimulation.",
"The objective was to compare the efficacy and complications of intravaginal misoprostol application with oxytocin infusion for induction of labor in advanced aged pregnancies with a Bishop score of < 6.\n A hundred advanced aged (> or = 35 years) pregnant patients with a Bishop score of < 6 were randomized into two groups. The first group (50 patients) received 50 microg intravaginal misoprostol four times with 4 h intervals and the second group received oxytocin infusion for induction of labor starting from 2 mIU/min and was increased every 30 min with 2 mIU/min increments up to a maximum of 40 mIU/min. The time from induction to delivery, the route of delivery, fetal outcome, and maternal complications were recorded. Statistical analyses were performed using the Mann-Whitney U, Chi-squared and t tests to determine differences between the two groups. A p value < or = 0.05 was considered significant.\n Misoprostol was superior for induction of labor in advanced aged pregnancies with Bishop score of < 6, as the mean time from induction to delivery was 9.61 +/- 4.12 h and 11.46 +/- 4.86 h in the misoprostol and oxytocin groups respectively, with a significant difference between the groups (p = 0.04). The rate of vaginal delivery was higher in the misoprostol group (84.0%) than in the oxytocin group (80.0%), but the difference did not reach significance (p = 0.60). The rates of placental abruption and postpartum hemorrhage were similar in both groups and no cases of uterine rupture occurred. The 1- and 5-min mean Apgar scores were 6.98 +/- 1.17 to 9.08 +/- 0.99 and 6.88 +/- 1.81 to 9.00 +/- 1.35 in the misoprostol and oxytocin groups respectively, with no significant differences between the groups (p = 0.74, p = 0.83). No cases of asphyxia were present. The rate of admission to the neonatal intensive care unit was similar in both groups.\n Intravaginal misoprostol seems to be an alternative method to oxytocin in the induction of labor in advanced aged pregnant women with low Bishop scores, as it is efficacious, cheap, and easy to use. But large studies are necessary to clarify safety with regard to the rare complications such as uterine rupture.",
"To compare three methods of labour induction.\n Randomised controlled trial.\n Academic hospitals in Johannesburg, South Africa.\n Women with intact membranes due for induction of labour.\n Randomised, sealed opaque envelopes were used to allocate women to labour induction with extra-amniotic Foley catheter/titrated oral misoprostol solution (N = 174), titrated oral misoprostol solution alone (N = 176), or vaginal dinoprostone (N = 176). Misoprostol was dissolved in water and 20-40 g was given 2-hourly.\n These were failure to deliver vaginally within 24 hours, additional measures for induction or augmentation of labour, analgesia, and maternal and fetal complications.\n In the Foley catheter group, misoprostol was required in all but 1 case. Failure to deliver vaginally within 24 hours was similar for the three groups (79/174 v. 70/176 v. 70/176 respectively). Labour augmentation, caesarean section and instrumental delivery were used somewhat more frequently in the Foley/misoprostol group than in the misoprostol alone group, but these differences were not statistically significant. More analgesia was used in the Foley catheter/misoprostol group than in the misoprostol group (64/172 v. 46/175). Side-effects and neonatal complications were similar for the three groups.\n Use of extra-amniotic Foley catheter placement showed no measurable benefits over the use of oral misoprostol alone, or vaginal dinoprostone."
] |
Vaginal misoprostol in doses above 25 mcg four-hourly was more effective than conventional methods of labour induction, but with more uterine hyperstimulation. Lower doses (25 mcg four-hourly or less) were similar to conventional methods in effectiveness and risks. The authors request information on cases of uterine rupture known to readers. The vaginal route should not be researched further as another Cochrane review has shown that the oral route of administration is preferable to the vaginal route. Professional and governmental bodies should agree guidelines for the use of misoprostol, based on the best available evidence and local circumstances.
[Note: The 27 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]
|
CD002311
|
[
"10212082",
"9722255",
"9121852",
"11158452",
"9713447",
"9773910",
"15833887"
] |
[
"Randomised controlled study of early use of inhaled corticosteroid in preterm infants with respiratory distress syndrome.",
"Efficacy of sequential early systemic and inhaled corticosteroid therapy in the prevention of chronic lung disease of prematurity.",
"Effectiveness of budesonide aerosol in ventilator-dependent preterm babies: a preliminary report.",
"A multicenter, randomized open study of early corticosteroid treatment (OSECT) in preterm infants with respiratory illness: comparison of early and late treatment and of dexamethasone and inhaled budesonide.",
"Randomised controlled trial of inhaled corticosteroids in patients with chronic obstructive pulmonary disease.",
"Efficacy of corticosteroids in acute bronchiolitis: short-term and long-term follow-up.",
"Fluticasone inhalation in moderate cases of bronchopulmonary dysplasia."
] |
[
"To investigate the therapeutic efficacy of inhaled fluticasone propionate, started on day 1 of age, on ventilated preterm infants with respiratory distress syndrome.\n Starting within 24 hours of age, ventilated preterm infants (gestation < 32 weeks, birthweight < 1.5 kg) with respiratory distress syndrome were given a 14 day course (two puffs, 12 hourly) of either fluticasone propionate (250 microg/puff) (group 1, n=27) or placebo (group 2, n=26) with a metered dose inhaler-spacer device. Response to treatment was assessed by the rate of successful extubation by days 7 and 14 of age, changes in respiratory system mechanics, death, occurrence of chronic lung disease, and other neonatal complications.\n More infants in the treatment group were successfully extubated by 14 days of age than those in the placebo group (17/27 vs 8/26; p = 0.038). The treated infants also showed a more significant improvement in respiratory system compliance during the first 14 days of life. The two groups, however, did not differ significantly in their need for systemic steroids after day 14 of age, death, or the occurrence of chronic lung disease. The treatment was not associated with any increase in neonatal complications, including those attributable to steroid induced side effects.\n These results provide preliminary evidence that early treatment with inhaled corticosteroids may be beneficial to ventilated preterm infants with respiratory distress. Further study of its use in a large scale randomised trial is warranted.",
"In order to assess the efficacy of a combination of systemic and nebulized corticosteroids in reducing the incidence and severity of chronic lung disease (CLD) in very low birthweight (VLBW) infants, 60 ventilator-dependent infants < or = 1500 g were randomly assigned to receive either steroids or placebo as of 7 d. The steroid group (n = 30, GA = 25.8 +/- 1.6 weeks, BW = 731 +/- 147 g) received systemic dexamethasone for 3 d, followed by nebulized budesonide for 18 d. Control infants (n = 30, GA = 25.9 +/- 1.8 weeks, BW = 796 +/- 199 g) received systemic and inhaled saline. Steroid-treated infants required less ventilatory support between 9 and 17 d (p < 0.01), and had greater lung compliance at 10 d (p = 0.01), but not subsequently. CLD incidence at 36 weeks was 45.5% vs 56.0% in controls, and fewer steroid-treated infants required dexamethasone rescue (23.3% vs 56.7%, p = 0.017). Survival to discharge was similar (73.3% vs 83.3%), as were the durations of mechanical ventilation, supplemental oxygen use, and hospitalization. Tracheal effluent elastase/albumin ratios and serum cortisol values did not differ between groups, and no adverse effects were noted. We conclude that early dexamethasone administration was associated with improved pulmonary function, which was not sustained with nebulized budesonide. However, the steroid regimen studied reduced the need for dexamethasone rescue in infants with CLD.",
"The aim of this randomized, double-blind, placebo-controlled trial was to assess the short-term effect of a topical glucocorticoid (budesonide 600 mu g twice daily) vs. placebo administered by metered dose inhaler (MDL) and spacer (Aerochamber MV15) directly into endotracheal tube of intubated infants for 7 days. Twenty preterm infants (mean birthweight, 1,030 g; mean gestational age, 27.3 weeks)who still needed assisted ventilation at 14 days of age were randomly assigned to receive budesonide (n=9) or placebo (n=11) and completed the study. The primary outcome was the need for mechanical ventilation after 7 days of treatment. Other outcome variables included ventilator settings, blood gases, serum cortisol levels, and bronchoalveolar lavage inflammatory cell counts. No ventilated infant was extubated during the study period. The treatment group showed significant improvements in mean peak inspiratory pressure, ventilator efficiency index, and (A-a) oxygen difference. There were no changes in the placebo group. Serum cortisol levels and bronchoalveolar lavage cell counts did not change significantly during study period. There was no difference in side effects between the groups. This trial demonstrates that topical budesonide administered by MDL and Aerochamber produces clinical improvement in ventilated preterm infants, without glucocorticoid side effects.",
"To compare early (<3 days) with late (>15 days) steroid therapy and dexamethasone with inhaled budesonide in very preterm infants at risk of developing chronic lung disease.\n Five hundred seventy infants from 47 neonatal intensive care units were enrolled. Criteria for enrollment included gestational age <30 weeks, postnatal age <72 hours, and need for mechanical ventilation and inspired oxygen concentration >30%. Infants were randomly allocated to 1 of 4 treatment groups in a factorial design: early (<72 hours) dexamethasone, early budesonide, delayed selective (>15 days) dexamethasone, and delayed selective budesonide. Dexamethasone was given in a tapering course beginning with 0.50 mg/kg/day in 2 divided doses for 3 days reducing by half until 12 days of therapy had elapsed. Budesonide was administered by metered dose inhaler and a spacing chamber in a dose of 400 microg/kg twice daily for 12 days. Delayed selective treatment was started if infants needed mechanical ventilation and >30% oxygen for >15 days. The factorial design allowed 2 major comparisons: early versus late treatment and systemic dexamethasone versus inhaled budesonide. The primary outcome was death or oxygen dependency at 36 weeks and analysis was on an intention-to-treat basis. Secondary outcome measures included death or major cerebral abnormality, duration of oxygen treatment, and complications of prematurity. Adverse effects were also monitored daily.\n There were no significant differences among the groups for the primary outcome. Early steroid treatment was associated with a lower primary outcome rate (odds ratio [OR]: 0.85; 95% confidence interval [CI]: 0.61,1.18) but even after adjustment for confounding variables the difference remained nonsignificant. Dexamethasone-treated infants also had a lower primary outcome rate (OR: 0.86; 95% CI: 0.62,1.20) but again this difference remained not significant after adjustment. For death before discharge, dexamethasone and early treatment had worse outcomes than budesonide and delayed selective treatment (OR: 1.42; 95% CI: 0.93,2.16; OR: 1.51; 95% CI: 0.99,2.30 after adjustment, respectively) with the results not quite reaching significance. Duration of supplementary oxygen was shorter in the early dexamethasone group (median: 31 days vs 40-44 days). Early dexamethasone was also associated with increased weight loss during the first 12 days of treatment (52 g vs 3 g) compared with early budesonide, but over 30 days there was no difference. In the early dexamethasone group, there was a reduced incidence of persistent ductus arteriosus (34% vs 52%-59%) and an increased risk of hyperglycemia (55% vs 29%-34%) compared with the other 3 groups. Dexamethasone was associated with an increased risk of hypertension and gastrointestinal problems compared with budesonide but only the former attained significance.\n Infants given early treatment and dexamethasone therapy had improved survival without chronic lung disease at 36 weeks compared with those given delayed selective treatment and inhaled budesonide, respectively, but results for survival to discharge were in the opposite direction; however, none of these findings attained statistical significance. Early dexamethasone treatment reduced the risk of persistent ductus arteriosus. Inhaled budesonide may be safer than dexamethasone, but there is no clear evidence that it is more or less effective.",
"Inhaled corticosteroids are known to be beneficial for patients with asthma, but their role in treating patients with stable chronic obstructive pulmonary disease (COPD) remains controversial. A study was undertaken to determine whether inhaled corticosteroids are of functional benefit in patients who did not show improvement with a trial of oral corticosteroids.\n In phase I patients with stable COPD were given a two week course of oral placebo followed by two weeks of prednisone 40 mg per day in a single blind manner to distinguish between responders and non-responders to oral corticosteroids. In phase II a double blind, randomised, parallel group trial of inhaled budesonide 1600 micrograms per day versus placebo was carried out in 79 nonresponders to oral corticosteroids. The primary outcome measure was forced expiratory volume in one second (FEV1), and secondary outcome measures were exercise capacity, dyspnoea with exertion, quality of life, peak expiration flow rate, and respiratory symptoms.\n Randomisation allocated 39 subjects to inhaled corticosteroids and 40 to placebo. There was no difference in the change in FEV1 from baseline between the treatment and placebo groups; mean difference -12 ml (95% CI -88 to 63) at three months and -4 ml (95% CI -95 to 87) at six months. The proportion of patients with a 15% or greater improvement was no higher among those receiving inhaled corticosteroids than in the placebo group at any of the follow up visits. Changes in secondary outcomes were also no different.\n Inhaled corticosteroids, even at high doses, were of no physiological or functional benefit in these patients with advanced COPD.",
"Corticosteroids continue to be used by many physicians to treat infants with bronchiolitis. The aim of this study was to examine the short-term and long-term efficacy of oral corticosteroid therapy when added to beta2-agonists in infants with mild to moderate bronchiolitis (defined as the first episode of wheezing associated with low grade fever, rhinitis, tachypnea, and increased respiratory effort in a previously healthy infant during the winter months). Infants with mild to moderate bronchiolitis, were randomly assigned to receive either oral prednisone (2 mg/kg/day) or placebo for 3 days. All patients received nebulized albuterol q.i.d. during this period. Upon admission and after 3 days of therapy, a clinical score was assigned based on respiratory rate, use of accessory muscle, and the presence of wheeze. Oxygen saturation (SaO2) was also measured. On day 7, we inquired as to the well-being of each child. Two years later, the development of chronic respiratory symptoms was assessed. Thirty-eight infants were enrolled in the study; 20 received prednisone and 18 received placebo. Both groups were similar in terms of age, duration of illness prior to enrollment, pretrial medication use, clinical severity of bronchiolitis, history of atopy, and family history of atopy. After 3 and 7 days of treatment, both groups showed similar clinical improvement and there were no statistically significant differences between the two groups in the clinical score or in the SaO2. No major side effects were observed. Two years later, 32% of the infants continued to suffer from chronic respiratory symptoms, with a similar prevalence in both groups. We conclude that a 3-day course of oral corticosteroids is of no benefit to infants with mild to moderate bronchiolitis who are also treated with an inhaled beta2-agonist.",
"This randomized, controlled trial was designed to determine the efficacy of inhaled fluticasone propionate on oxygen therapy weaning in a population of preterm infants who were born at <32 weeks of gestation and experienced moderate bronchopulmonary dysplasia (BPD).\n Thirty-two infants who were < or =32 weeks of gestation, had moderate BPD that required supplemental oxygen (fraction of inspired oxygen > or =0.25), and were aged between 28 and 60 days were randomized. Fluticasone propionate 125 microg twice daily for 3 weeks and once daily for a fourth week was delivered to infants who weighed between 500 and 1200 g. The dosage was doubled for infants who weighed > or =1200 g.\n Compared with placebo, treatment had no effect on either duration of supplemental O2 therapy or ventilatory support as assessed by survival analysis. At 28 days, a trend toward a lower cortisol/creatinine ratio in the treatment group was noted compared with placebo (25.1 +/- 18.9 vs 43 +/- 14.4). In the fluticasone group at 28 days, the systolic arterial pressure (78 +/- 3 vs 68 +/- 3 mm Hg) and diastolic arterial pressure (43 +/- 3.4 mm Hg vs 38 +/- 2.0 mm Hg) were higher compared with baseline fluticasone values. The chest radiograph score was lower than baseline (2.8 +/- 1.4 vs 3.7 +/- 2.2) in the fluticasone group at 28 days. This study has a statistical power of 1.0 to detect a significant difference in the duration of oxygen supplementation of >21 days between the study groups.\n We conclude that fluticasone propionate reduces neither supplemental O2 use nor the need for ventilatory support in this patient population. However, fluticasone does have a positive radiologic effect in lowering chest radiograph scores. In addition, our data point to a possible association among inhaled fluticasone treatment and higher arterial blood pressure. Thus, the results of this investigation do not support the use of inhaled corticosteroids in the treatment of oxygen-dependent infants who have established moderate BPD."
] |
Based on the results of the currently available evidence, inhalation corticosteroids initiated at ≥ 7 days of life for preterm infants at high risk of developing BPD cannot be recommended at this point in time. More and larger randomised, placebo-controlled trials are needed to establish the efficacy and safety of inhalation corticosteroids.
|
CD007969
|
[
"17597827",
"17551656",
"19578227",
"7612090",
"10591428",
"10839875"
] |
[
"Randomized controlled trial of light-emitting diode phototherapy.",
"Efficacy of new microprocessed phototherapy system with five high intensity light emitting diodes (Super LED).",
"Light emitting diodes versus compact fluorescent tubes for phototherapy in neonatal jaundice: a multi center randomized controlled trial.",
"Double phototherapy with high irradiance compared with single phototherapy in neonates with hyperbilirubinemia.",
"Comparison of the efficacy of conventional special blue light phototherapy and fiberoptic phototherapy in the management of neonatal hyperbilirubinaemia.",
"A new blue light-emitting phototherapy device: a prospective randomized controlled study."
] |
[
"We wished to compare the efficacy of light-emitting diode (LED) phototherapy with special blue fluorescent (BB) tube phototherapy in the treatment of neonatal hyperbilirubinemia.\n We randomly assigned 66 infants >or=35 weeks of gestation to receive phototherapy using an LED device or BB. In addition to phototherapy from above, all infants also received phototherapy from below using four BB tubes or a fiberoptic pad.\n After 15+/-5 h of phototherapy, the rate of decline in the total serum bilirubin (TSB) was 0.35+/-0.25 mg/dl/h in the LED group vs 0.27+/-0.25 mg/dl/h in the BB group (P=0.20).\n LED phototherapy is as effective as BB phototherapy in lowering serum bilirubin levels in term and near-term newborns.",
"To evaluate the efficacy of a microprocessed phototherapy (PT) system with five high intensity light emitting diodes (Super LED) for the treatment of neonatal hyperbilirubinemia of premature infants.\n Randomized clinical trial using Super LED phototherapy in the study group and twin halogen spotlight phototherapy in the control group. A stratified blocked randomization, based on birth weight, was performed. The duration of phototherapy and the rate of decrease of total serum bilirubin (TSB) concentration in the first 24 hours of treatment were the main outcome measures.\n We studied 88 infants, 44 in the Super LED group and 44 in the halogen spotlight PT group. The demographic characteristics of the patients in both groups were similar. Infants in the Super LED group had a similar mean initial serum bilirubin level (10.1+/-2.4 mg%) to those receiving halogen spotlight treatment (10.9+/-2.0 mg%). After 24 hours of treatment, the decrease in total serum bilirubin levels was significantly greater in the Super LED group (27.9 vs. 10.7%, p<0.01) and duration of phototherapy was significantly shorter in this group (36.8 h vs. 63.8 h, p<0.01). After 24 hours of treatment, a significantly greater number of patients receiving Super LED phototherapy had reached serum bilirubin concentrations low enough to allow withdrawal of treatment (23 vs. 10, p<0.01).\n Our results demonstrate that the efficacy of Super LED phototherapy for treating hyperbilirubinemia in premature infants was significantly better than halogen phototherapy.",
"To evaluate whether light-emitting diode (LED) phototherapy is as efficacious as compact fluorescent tube (CFT) phototherapy for the treatment of non-hemolytic jaundice in healthy term and late preterm neonates.\n Multi centre open label randomized controlled trial.\n Four tertiary care neonatal units.\n Healthy term and late preterm neonates with non-hemolytic jaundice.\n Single-surface LED or CFT phototherapy. PRIMARY OUTCOME VARIABLE: Duration of phototherapy.\n A total of 272 neonates were randomized to receive LED (n=142) or CFT (n=130) phototherapy. The baseline demographic and biochemical variables were similar in the two groups. The median duration of phototherapy (IQR) in the two groups was comparable (26 (22-36) h vs. 25(22-36) h; P=0.44). At any time point, a similar proportion of neonates were under phototherapy in the two groups (log-rank test, P=0.38). The rate of fall of serum total bilirubin (STB) during phototherapy and the incidence of failure of phototherapy were also not different. An equal proportion of neonates had a rebound increase in STB needing restarting of phototherapy. Side effects were rare, comparable in the two groups and included hypothermia, hyperthermia, rash, skin darkening and dehydration.\n LED and CFT phototherapy units were equally efficacious in the management of non-hemolytic hyperbilirubinemia in healthy term and late preterm neonates.",
"The purpose of this study is to compare the effectiveness of double phototherapy versus single conventional phototherapy in decreasing serum bilirubin levels in jaundiced neonates. Forty-two preterm infants who were less than 37 weeks' gestational age and less than 2000 g birthweight with nonhemolytic jaundice were alternately assigned to double phototherapy (n = 19) (Biliblanket, Ohmeda with irradiance of 33 to 35 microW/cm2/nm in addition to single conventional phototherapy with combination of three or four special blue and white lamps with irradiance of 7 to 9 microW/cm2/nm) or to single conventional phototherapy (n = 23) based on elevated serum bilirubin levels in the first week of life. Phototherapy was initiated at specific bilirubin levels in three weight stratifications. The groups were similar in clinical characteristics at study entry. The decrease in serum bilirubin levels was very significant in the double phototherapy group at 8 hours after the therapy (-29 +/- 18.8 versus 8.5 +/- 27 mumol/L; P < 0.001), at 16 hours after the therapy (-49.6 +/- 15.4 versus 3.4 +/- 39 mumol/L; p < 0.001), and at 24 hours after therapy (-71.8 +/- 18.8 versus -3.4 +/- 32.5 mumol/L; p < 0.001) compared with the conventional phototherapy group. The time taken for bilirubin levels to fall below the threshold level was 55 +/- 41 hours in the single group and 14 +/- 6 hours in the double group (p < 0.001). Double phototherapy was well tolerated. The Biliblanket when used in conjunction with single conventional phototherapy resulted in a faster decrease of serum bilirubin.(ABSTRACT TRUNCATED AT 250 WORDS)",
"The efficacy and usefulness of two types of phototherapy differing in the source, wavelength and irradiance of the light, conventional phototherapy consisting of special blue light and fiberoptic phototherapy, were compared in a relatively larger series of term newborns with non-haemolytic and more significant hyperbilirubinaemia than those in previous studies. In total, 108 newborns were allocated sequentially to receive either conventional phototherapy consisting of five special blue lamps or fiberoptic phototherapy. The average spectral irradiance measured at the skin surface level of newborns during the study period was significantly greater in the conventional phototherapy group. The special blue lamp of the conventional phototherapy unit had an emission spectrum almost identical to the bilirubin absorption spectrum, whereas the tungsten-halogen lamp of the fiberoptic phototherapy had a broad emission through the blue and green wavelengths (mainly in the green spectrum). Phototherapy was more effective in the conventional phototherapy group; the duration of exposure to phototherapy (h) was significantly shorter, and the overall bilirubin decline rate (as micromol/l/h and %/h) was significantly greater in the conventional phototherapy group. According to the nursing personnel, fiberoptic phototherapy was more comfortable than the conventional phototherapy frame because of the easier accessibility and handling of the infants during phototherapy. They complained of giddiness, nausea, glare, temporary blurring of vision and difficulty in detecting the skin colour changes of newborns with the blue light of the conventional phototherapy unit. Conventional phototherapy consisting of special blue fluorescent lamps with approximately twofold higher irradiance and an emission spectrum almost identical to the bilirubin absorption spectrum is preferable to fiberoptic phototherapy in the standard treatment of term newborns with non-haemolytic hyperbilirubinaemia.",
"To evaluate the efficacy of a new phototherapy light source with a narrow luminous blue spectrum. The device, made with high-intensity gallium nitride light-emitting diodes (LEDs), was compared with conventional phototherapy at similar light intensities.\n Two university-affiliated community hospitals in Jerusalem.\n Prospective open randomized study.\n Sixty-nine jaundiced, but otherwise healthy, term infants who met the entry criteria for phototherapy set by the American Academy of Pediatrics' Practice Parameter.\n The duration of phototherapy and the rate of decrease in total serum bilirubin (TSB) concentration.\n The mean TSB concentrations at initiation and termination of treatment did not differ between newborns receiving LED and those receiving conventional phototherapy. The duration of phototherapy and the rate of decrease in TSB concentration were not statistically different in the 2 groups. The average rate of decrease in TSB after adjustment by a linear regression analysis for confounding factors was -3.16 micromol/L/h (95% confidence limits -4.81, -1.51) in newborns receiving LED phototherapy compared with -2.19 micromol/L/h (-3.99, -0.40) in those treated with conventional phototherapy (P <.14). No side effects were noted in any of the newborns.\n The blue gallium nitride LED device is as effective as conventional phototherapy and is readily accepted by nursing staff. Future LED phototherapy devices can provide much higher irradiance, and thus greater efficacy, and offer a new highly versatile approach to the treatment of jaundice."
] |
LED light source phototherapy is efficacious in bringing down levels of serum total bilirubin at rates that are similar to phototherapy with conventional (compact fluorescent lamp (CFL) or halogen) light sources. Further studies are warranted for evaluating efficacy of LED phototherapy in neonates with haemolytic jaundice or in the presence of severe hyperbilirubinaemia (STB ≥ 20 mg/dL).
|
CD005367
|
[
"9037222",
"17130328"
] |
[
"A double-blind study of perioperative steroid requirements in secondary adrenal insufficiency.",
"Minor infection encouraged by steroid administration during cardiac surgery."
] |
[
"Patients treated long-term with supraphysiologic doses of glucocorticoids experience secondary adrenal insufficiency and are routinely given large doses of steroids in the perioperative period to prevent hypotension. Because the dose of steroids required to prevent hypotension is not known, we conducted a randomized, double-blind study to determine whether patients treated long-term with glucocorticoids actually require increased steroids in the perioperative period.\n Patients who had been taking at least 7.5 mg prednisone daily for several months and had secondary adrenal insufficiency as defined by adrenocorticotropic hormone testing formed the study population. Patients were randomized to two groups. One group received perioperative injections of saline solution alone; the other received perioperative saline solution and cortisol. All patients received their usual daily prednisone dose throughout the study.\n Six patients were in the steroid-treated group and 12 were in the saline-treated group. Most subjects underwent major operations such as joint replacements, abdominal operations, and miscellaneous other procedures. Two patients had hypotension, one in each group. Hypotension resolved with volume replacement in both patients. The average pulse rates and blood pressures were similar in both groups during the perioperative period.\n Patients with secondary adrenal insufficiency do not experience hypotension or tachycardia caused by inadequate glucocorticoid levels when given only their daily dose of steroids for surgical procedures.",
"The aim of this study was to investigate whether steroid administration would increase the risk of postoperative infection. Sixty adults who underwent elective cardiac surgery under cardiopulmonary bypass were prospectively randomized into two groups. Thirty-one patients received hydrocortisone (50 mg x kg(-1)) before and after cardiopulmonary bypass, the other 29 served as controls. Various hemodynamic and pulmonary measurements were obtained perioperatively, and the white blood cell counts and levels of C-reactive protein were checked up to the 14(th) postoperative day. Steroid administration did not have any favorable effects during the perioperative period. Re-administration of antibiotics was needed in 7 patients (22.6%) after the 7(th) postoperative day in the steroid group, and in 3 (10.3%) in the control group. The peak white cell counts and C-reactive protein levels after the 7(th) postoperative day were significantly higher in the steroid group. Steroid administration offered no clinical benefit to patients undergoing cardiac surgery with cardiopulmonary bypass, and it may encourage minor infections in the late postoperative period."
] |
Owing to the small number of patients, the results may not be representative. Based on current available evidence, we are unable to support or refute the use of supplemental perioperative steroids for patients with adrenal insufficiency during surgery.
|
CD000935
|
[
"2319363"
] |
[
"Recognizing the onset of labor."
] |
[
"An experimental study compared the use of an educational technique based on patient participation with routine instructions to prepare patients to recognize the onset of active labor. The number of visits to the labor suite that resulted in the patient being discharged undelivered was significantly lower in patients who received the educational intervention. The study revealed that, without any increase in time, nurses can prepare patients to make judgments about the need for hospitalization."
] |
There is not enough evidence to evaluate the use of a specific set of criteria for self-diagnosis of active labour.
|
CD003149
|
[
"7791837"
] |
[
"A comparison of conservative and aggressive transfusion regimens in the perioperative management of sickle cell disease. The Preoperative Transfusion in Sickle Cell Disease Study Group."
] |
[
"Preoperative transfusions are frequently given to prevent perioperative morbidity in patients with sickle cell anemia. There is no consensus, however, on the best regimen of transfusions for this purpose.\n We conducted a multicenter study to compare the rates of perioperative complications among patients randomly assigned to receive either an aggressive transfusion regimen designed to decrease the hemoglobin S level to less than 30 percent (group 1) or a conservative regimen designed to increase the hemoglobin level to 10 g per deciliter (group 2).\n Patients undergoing a total of 604 operations were randomly assigned to group 1 or group 2. The severity of the disease, compliance with the protocol, and the types of operations were similar in the two groups. The preoperative hemoglobin level was 11 g per deciliter in group 1 and 10.6 g per deciliter in group 2. The preoperative value for hemoglobin S was 31 percent in group 1 and 59 percent in group 2. The most frequent operations were cholecystectomies (232), head and neck surgery (156), and orthopedic surgery (72). With the exception of transfusion-related complications, which occurred in 14 percent of the operations in group 1 and in 7 percent of those in group 2, the frequency of serious complications was similar in the two groups (31 percent in group 1 and 35 percent in group 2). The acute chest syndrome developed in 10 percent of both groups and resulted in two deaths in group 1. A history of pulmonary disease and a higher risk associated with surgery were significant predictors of the acute chest syndrome.\n A conservative transfusion regimen was as effective as an aggressive regimen in preventing perioperative complications in patients with sickle cell anemia, and the conservative approach resulted in only half as many transfusion-associated complications."
] |
While in general, conservative therapy appears to be as effective as aggressive therapy in preparation for surgery in people with sickle cell disease, further research is needed to examine the optimal regimen for different surgical types, and to address whether preoperative transfusion is needed in all surgical situations.
|
CD007146
|
[
"16183652",
"12568412",
"17656420",
"15501836",
"16088114",
"17613583",
"16274368",
"12588571",
"20492040",
"17302660",
"16641143",
"21214623",
"18629569",
"20060665",
"12851185",
"8617895",
"15814861",
"20230348",
"15341550",
"18662214",
"17473911",
"12130606",
"19054193",
"19675115",
"15963186",
"22503739",
"11264206",
"12006310",
"9366737",
"14687346",
"16078954",
"15490272",
"20823124",
"20625015",
"12588572",
"17661956",
"21143436",
"21051772",
"20128337",
"18166695",
"17119004",
"19221130",
"20854564",
"18195202",
"11890582",
"14695863",
"16125805",
"11918228",
"20421240",
"19767629",
"11527475",
"15381507",
"15368824",
"17329285",
"18283231",
"10671804",
"20460620",
"21507049",
"8078528",
"15144369",
"8150304",
"21450224",
"20510973",
"16959668",
"15528779",
"19392952",
"14695864",
"16696748",
"19507291",
"10841179",
"17998225",
"12495822",
"16813773",
"10023893",
"21369788",
"18043700",
"11039967",
"15860827",
"16505262",
"16600924",
"15031238",
"18083724",
"18808597",
"19011727",
"22544817",
"11563205",
"20202271",
"15716246",
"21044715",
"19651265",
"16645293",
"20458090",
"15151914",
"22214657",
"4003187",
"12757571",
"17397426",
"20598577",
"12020141",
"20817936"
] |
[
"Randomised controlled trial of prevention of falls in people aged > or =75 with severe visual impairment: the VIP trial.",
"Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial.",
"Does vitamin D stop inpatients falling? A randomised controlled trial.",
"Vitamin D supplementation improves neuromuscular function in older people who fall.",
"Low-dose vitamin D prevents muscular atrophy and reduces falls and hip fractures in women after stroke: a randomized controlled trial.",
"Effects of exercise and nutrition on postural balance and risk of falling in elderly people with decreased bone mineral density: randomized controlled trial pilot study.",
"Should older people in residential care receive vitamin D to prevent falls? Results of a randomized trial.",
"A randomized, controlled trial of quadriceps resistance exercise and vitamin D in frail older people: the Frailty Interventions Trial in Elderly Subjects (FITNESS).",
"Community-based interventions to reduce falls among older adults in Taiwan - long time follow-up randomised controlled study.",
"A higher dose of vitamin d reduces the risk of falls in nursing home residents: a randomized, multiple-dose study.",
"Vitamin D supplementation and the prevention of fractures and falls: results of a randomised trial in elderly people in residential accommodation.",
"Reducing the fear of falling among community-dwelling elderly adults through cognitive-behavioural strategies and intense Tai Chi exercise: a randomized controlled trial.",
"Effects of a long-term vitamin D and calcium supplementation on falls and parameters of muscle function in community-dwelling older individuals.",
"Does daily vitamin D 800 IU and calcium 1000 mg supplementation decrease the risk of falling in ambulatory women aged 65-71 years? A 3-year randomized population-based trial (OSTPRE-FPS).",
"Community-based group exercise improves balance and reduces falls in at-risk older people: a randomised controlled trial.",
"Reducing frailty and falls in older persons: an investigation of Tai Chi and computerized balance training. Atlanta FICSIT Group. Frailty and Injuries: Cooperative Studies of Intervention Techniques.",
"Tai Chi and fall reductions in older adults: a randomized controlled trial.",
"A cluster randomised controlled trial to prevent injury due to falls in a residential aged care population.",
"The effectiveness of a community-based program for reducing the incidence of falls in the elderly: a randomized trial.",
"Lack of effectiveness of a multidisciplinary fall-prevention program in elderly people at risk: a randomized, controlled trial.",
"Preventing fractures among older people living in institutional care: a pragmatic randomised double blind placebo controlled trial of vitamin D supplementation.",
"Randomised factorial trial of falls prevention among older people living in their own homes.",
"Lack of effect of Tai Chi Chuan in preventing falls in elderly people living at home: a randomized clinical trial.",
"Effectiveness of a video-based exercise programme to reduce falls and improve health-related quality of life among older adults discharged from hospital: a pilot randomized controlled trial.",
"Effects of Sun-style Tai Chi exercise on physical fitness and fall prevention in fall-prone older adults.",
"Effects of a multifactorial falls prevention program for people with stroke returning home after rehabilitation: a randomized controlled trial.",
"Effectiveness and economic evaluation of a nurse delivered home exercise programme to prevent falls. 1: Randomised controlled trial.",
"Evaluation of a nurse-led falls prevention programme versus usual care: a randomized controlled trial.",
"Randomised controlled trial of a general practice programme of home based exercise to prevent falls in elderly women.",
"Intense tai chi exercise training and fall occurrences in older, transitionally frail adults: a randomized, controlled trial.",
"The effect of an individualized fall prevention program on fall risk and falls in older people: a randomized, controlled trial.",
"Randomized controlled trial of exercise intervention for the prevention of falls in community-dwelling elderly Japanese women.",
"A multicentre randomised controlled trial of day hospital-based falls prevention programme for a screened population of community-dwelling older people at high risk of falls.",
"Multifactorial intervention to reduce falls in older people at high risk of recurrent falls: a randomized controlled trial.",
"Preventing falls in community-dwelling frail older people using a home intervention team (HIT): results from the randomized Falls-HIT trial.",
"A randomized, controlled trial of tai chi for the prevention of falls: the Central Sydney tai chi trial.",
"A randomized controlled trial of a multifactorial falls prevention intervention for older fallers presenting to emergency departments.",
"A randomized trial of a multifaceted intervention to reduce falls among community-dwelling adults.",
"Multifactorial intervention with balance training as a core component among fall-prone older adults.",
"Effectiveness of a community-based multifactorial intervention on falls and fall risk factors in community-living older adults: a randomized, controlled trial.",
"A randomised controlled trial of a home based exercise programme to reduce the risk of falling among people with Parkinson's disease.",
"A multifactorial intervention for the prevention of falls in psychogeriatric nursing home patients, a randomised controlled trial (RCT).",
"LiFE Pilot Study: A randomised trial of balance and strength training embedded in daily life activity to reduce falls in older adults.",
"Effects of ergocalciferol added to calcium on the risk of falls in elderly high-risk women.",
"Preventing falls in older people: outcome evaluation of a randomized controlled trial.",
"A randomised, controlled comparison of different calcium and vitamin D supplementation regimens in elderly women after hip fracture: The Nottingham Neck of Femur (NONOF) Study.",
"The effects of Tai Chi Chuan on physiological function and fear of falling in the less robust elderly: an intervention study for preventing falls.",
"Can vitamin D supplementation reduce the risk of fracture in the elderly? A randomized controlled trial.",
"Randomized trial of domiciliary versus center-based rehabilitation: which is more effective in reducing falls and improving quality of life in older fallers?",
"Community-based intervention to optimise falls risk management: a randomised controlled trial.",
"A randomized trial of exercise programs among older individuals living in two long-term care facilities: the FallsFREE program.",
"Falls prevention in residential care homes: a randomised controlled trial.",
"Evidence-based clinical practice in falls prevention: a randomised controlled trial of a falls prevention service.",
"Comparison of the effectiveness of two programmes on older adults at risk of falling: unsupervised home exercise and supervised group exercise.",
"A randomized controlled trial of fall prevention by a high-intensity functional exercise program for older people living in residential care facilities.",
"A randomized controlled trial of fall prevention strategies in old peoples' homes.",
"Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial.",
"Evaluating the use of a targeted multiple intervention strategy in reducing patient falls in an acute care hospital: a randomized controlled trial.",
"A multifactorial intervention to reduce the risk of falling among elderly people living in the community.",
"Effectiveness of home visit falls prevention strategy for Taiwanese community-dwelling elders: randomized trial.",
"Preventing falls among community-dwelling older persons: results from a randomized trial.",
"Multifactorial fall prevention for pairs of frail community-dwelling older fallers and their informal caregivers: a dead end for complex interventions in the frailest fallers.",
"Comparison of telecommunication, community, and home-based Tai Chi exercise programs on compliance and effectiveness in elders at risk for falls.",
"Community-based tai chi and its effect on injurious falls, balance, gait, and fear of falling in older people.",
"Low-intensity exercise and reduction of the risk for falls among at-risk elders.",
"Effect of a risk-based multifactorial fall prevention program on the incidence of falls.",
"The efficacy of a specific balance-strategy training programme for preventing falls among older people: a pilot randomised controlled trial.",
"A randomized trial of a multicomponent home intervention to reduce functional difficulties in older adults.",
"An outpatient multifactorial falls prevention intervention does not reduce falls in high-risk elderly Danes.",
"Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women.",
"Effect of annual intramuscular vitamin D on fracture risk in elderly men and women--a population-based, randomized, double-blind, placebo-controlled trial.",
"[Effectiveness of falls prevention strategies for elderly subjects who live in the community with performance assessment of physical activities (before-after)].",
"Effects of exercise programs on falls and mobility in frail and pre-frail older adults: A multicenter randomized controlled trial.",
"Prevention of falls in the elderly trial (PROFET): a randomised controlled trial.",
"Does increased sunlight exposure work as a strategy to improve vitamin D status in the elderly: a cluster randomised controlled trial.",
"Multivitamin supplementation improves nutritional status and bone quality in aged care residents.",
"Effects of a programme of multifactorial home visits on falls and mobility impairments in elderly people at risk: randomised controlled trial.",
"Randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D3) for prevention of fractures in primary care.",
"Effect of cholecalciferol plus calcium on falling in ambulatory older men and women: a 3-year randomized controlled trial.",
"Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial.",
"Effectiveness of targeted falls prevention programme in subacute hospital setting: randomised controlled trial.",
"Educating nursing home staff on fracture prevention: a cluster randomised trial.",
"Effectiveness of a falls-and-fracture nurse coordinator to reduce falls: a randomized, controlled trial of at-risk older adults.",
"Preventative effect of exercise against falls in the elderly: a randomized controlled trial.",
"Exercise to enhance mobility and prevent falls after stroke: the community stroke club randomized trial.",
"A randomized controlled trial of a community-based consultation service to prevent falls.",
"The effects and costs of a multifactorial and interdisciplinary team approach to falls prevention for older home care clients 'at risk' for falling: a randomized controlled trial.",
"Patients with recurrent falls attending Accident & Emergency benefit from multifactorial intervention--a randomised controlled trial.",
"Efficacy of a short multidisciplinary falls prevention program for elderly persons with osteoporosis and a fall history: a randomized controlled trial.",
"Reducing risk of falling in older people discharged from hospital: a randomized controlled trial comparing seated exercises, weight-bearing exercises, and social visits.",
"A five-week exercise program can reduce falls and improve obstacle avoidance in the elderly.",
"Effect of high-dosage cholecalciferol and extended physiotherapy on complications after hip fracture: a randomized controlled trial.",
"Using targeted risk factor reduction to prevent falls in older in-patients: a randomised controlled trial.",
"Effect of distributing an evidence-based guideline for prevention of osteoporosis on health education programs in municipal health centers: a randomized controlled trial.",
"Do vitamin D supplements improve the physical capabilities of elderly hospital patients?",
"Reducing fear of falling in seniors through education and activity programs: a randomized trial.",
"A randomized, controlled trial of fall prevention programs and quality of life in older fallers.",
"An open-label trial comparing alendronate and alphacalcidol in reducing falls and hip fractures in disabled stroke patients.",
"Fall and injury prevention in older people living in residential care facilities. A cluster randomized trial.",
"The Whitehorse NoFalls trial: effects on fall rates and injurious fall rates."
] |
[
"To assess the efficacy and cost effectiveness of a home safety programme and a home exercise programme to reduce falls and injuries in older people with low vision.\n Randomised controlled trial.\n Dunedin and Auckland, New Zealand.\n 391 women and men aged > or =75 with visual acuity of 6/24 or worse who were living in the community; 92% (361 of 391) completed one year of follow-up.\n Participants received a home safety assessment and modification programme delivered by an occupational therapist (n = 100), an exercise programme prescribed at home by a physiotherapist plus vitamin D supplementation (n = 97), both interventions (n = 98), or social visits (n = 96).\n Numbers of falls and injuries resulting from falls, costs of implementing the home safety programme.\n Fewer falls occurred in the group randomised to the home safety programme but not in the exercise programme (incidence rate ratios 0.59 (95% confidence interval 0.42 to 0.83) and 1.15 (0.82 to 1.61), respectively). However, within the exercise programme, stricter adherence was associated with fewer falls (P = 0.001). A conservative analysis showed neither intervention was effective in reducing injuries from falls. Delivering the home safety programme cost NZ650 dollars (234 pounds sterling, 344 euros, US432 dollars) (at 2004 prices) per fall prevented.\n The home safety programme reduced falls and was more cost effective than an exercise programme in this group of elderly people with poor vision. The Otago exercise programme with vitamin D supplementation was not effective in reducing falls or injuries in this group, possibly due to low levels of adherence. Trial registration number ISRCTN15342873.",
"Specific receptors for vitamin D have been identified in human muscle tissue. Cross-sectional studies show that elderly persons with higher vitamin D serum levels have increased muscle strength and a lower number of falls. We hypothesized that vitamin D and calcium supplementation would improve musculoskeletal function and decrease falls. In a double-blind randomized controlled trial, we studied 122 elderly women (mean age, 85.3 years; range, 63-99 years) in long-stay geriatric care. Participants received 1200 mg calcium plus 800 IU cholecalciferol (Cal+D-group; n = 62) or 1200 mg calcium (Cal-group; n = 60) per day over a 12-week treatment period. The number of falls per person (0, 1, 2-5, 6-7, >7 falls) was compared between the treatment groups. In an intention to treat analysis, a Poisson regression model was used to compare falls after controlling for age, number of falls in a 6-week pretreatment period, and baseline 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum concentrations. Among fallers in the treatment period, crude excessive fall rate (treatment - pretreatment falls) was compared between treatment groups. Change in musculoskeletal function (summed score of knee flexor and extensor strength, grip strength, and the timed up&go test) was measured as a secondary outcome. Among subjects in the Cal+D-group, there were significant increases in median serum 25-hydroxyvitamin D (+71%) and 1,25-dihydroxyvitamin D (+8%). Before treatment, mean observed number of falls per person per week was 0.059 in the Cal+D-group and 0.056 in the Cal-group. In the 12-week treatment period, mean number of falls per person per week was 0.034 in the Cal+D-group and 0.076 in the Cal-group. After adjustment, Cal+D-treatment accounted for a 49% reduction of falls (95% CI, 14-71%; p < 0.01) based on the fall categories stated above. Among fallers of the treatment period, the crude average number of excessive falls was significantly higher in the Cal-group (p = 0.045). Musculoskeletal function improved significantly in the Cal+D-group (p = 0.0094). A single intervention with vitamin D plus calcium over a 3-month period reduced the risk of falling by 49% compared with calcium alone. Over this short-term intervention, recurrent fallers seem to benefit most by the treatment. The impact of vitamin D on falls might be explained by the observed improvement in musculoskeletal function.",
"Vitamin D deficiency is common in older people and may increase risk of falls and fracture. Hospital inpatients are at particular risk of falling. Previous studies suggest that vitamin D improves neuromuscular function and reduces falls.\n To determine whether routine supplementation with vitamin D plus calcium reduces numbers of fallers and falls in a cohort of hospital admissions while they are inpatients.\n Randomised, double-blind, controlled study. Participants: two hundred and five acute admissions >65 years to a geriatric medical unit.\n Patients were randomised to intervention of daily vitamin D 800 iu plus calcium 1,200 mg or control group of daily calcium 1,200 mg, until discharge or death.\n Baseline characteristics were similar in both groups with a median age 84 years and a median length of stay = 30 days (IQR 14.75-71.00). In a pre-selected sub-group (54/205 participants), median admission vitamin D level = 22.00 nmol/l (IQR 15.00-30.50). This did not significantly increase in the treatment versus control group. Median study drug adherence = 88%, with no significant difference between study groups (Mann-Whitney: P = 0.711). Although there were fewer fallers in the vitamin D cohort, this did not reach statistical significance (vitamin D: calcium = 36:45 fallers; RR 0.82 (CI 0.59-1.16). Neither the mean number of falls (vitamin D: calcium = 1.040:1.155; Mann-Whitney P = 0.435) or time to first fall (Log-rank test P = 0.377) differed between groups.\n In a population of geriatric hospital inpatients, vitamin D did not reduce the number of fallers. Routine supplementation cannot be recommended to reduce falls in this group.",
"vitamin D supplementation reduces the incidence of fractures in older adults. This may be partly mediated by effects of vitamin D on neuromuscular function.\n to determine the effects of vitamin D supplementation on aspects of neuromuscular function known to be risk factors for falls and fractures.\n randomised, double-blind, placebo-controlled study.\n falls clinic taking referrals from general practitioners and accident and emergency department.\n 139 ambulatory subjects (>/=65 years) with a history of falls and 25-hydroxyvitamin D (25OHD) </=12 microg/l. Intervention: patients were randomised to receive a single intramuscular injection of 600,000 i.u. ergocalciferol or placebo.\n assessments including biochemistry, postural sway, choice reaction time (CRT), aggregate functional performance time (AFPT), and quadriceps strength were carried out at baseline and 6 months post-intervention.\n baseline characteristics were comparable between both groups. 25OHD in the treatment group increased significantly at 6 months. AFPT deteriorated in the control group and improved in the intervention group, representing a significant difference between groups (+6.6 s versus -2.0 s, t = 2.80, P < 0.05). Similar changes were observed for CRT (-0.06 s versus +0.41 s, t = -2.52, P < 0.01) and postural sway (+0.0025 versus -0.0138, t = 2.35, P < 0.02). There was no significant difference in muscle strength change between groups (-10 N versus -2 N, t = -1.26, ns). A significant correlation between change in AFPT and change in 25OHD levels was observed (r = 0.19, P = 0.03). There was no significant difference in the number of falls (0.39 versus 0.24, t = 1.08, P = 0.28) or fallers (14 versus 11, P = 0.52) between two groups.\n vitamin D supplementation, in fallers with vitamin D insufficiency, has a significant beneficial effect on functional performance, reaction time and balance, but not muscle strength. This suggests that vitamin D supplementation improves neuromuscular or neuroprotective function, which may in part explain the mechanism whereby vitamin D reduces falls and fractures.",
"Vitamin D supplementation is suggested to reduce the risk of falls among ambulatory or institutionalized elderly subjects. The present study was undertaken to address the reduced risk of falls and hip fractures in patients with long-standing stroke by vitamin D supplementation.\n Ninety-six elderly women with poststroke hemiplegia were followed for two years. Patients were randomly assigned to one of the two groups, and 48 patients received 1,000 IU ergocalciferol daily, and the remaining 48 received placebo. The number of falls per person and incidence of hip fractures were compared between the two groups. Strength and tissue ATPase of skeletal muscles on the nonparetic side were assessed before and after the study.\n At baseline, serum 25-hydroxyvitamin D levels were in the deficient range (<10 ng/ml) in all patients; and vitamin D treatment enhanced serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels. Vitamin D treatment accounted for a 59% reduction in falls (95% CI, 28-81%; p = 0.003). There were increases in the relative number and size of type II muscle fibers and improved muscle strength in the vitamin D-treated group. Hip fractures occurred in 4 of 48 placebo group and 0 in 48 vitamin D2 group during the 2-year study period (log-rank, p = 0.049).\n Vitamin D may increase muscle strength by improving atrophy of type II muscle fibers, which may lead to decreased falls and hip fractures.\n Copyright (c) 2005 S. Karger AG, Basel.",
"To compare the effect of calcium/vitamin D supplements with a combination of calcium/vitamin D supplements and exercise/protein on risk of falling and postural balance.\n Randomized clinical trial.\n University hospital physiotherapy department.\n Twenty-four independently living elderly females aged 65 years and older with osteopenia or osteoporosis and mean total hip T-score (SD) of -1.8 (0.8).\n A three-month programme consisting of exercise/protein including training of muscular strength, co-ordination, balance and endurance. Calcium/ vitamin D was supplemented in all participants for a 12-month period.\n Assessment took place prior to and following the months 3, 6, 9 and at the end of the study; primary dependent variables assessed were risk of falling (Berg Balance Test) and postural balance (forceplate). Secondary measures included body composition, strength, activity level, number of falls, bone mineral content, biochemical indices, nutritional status and general health.\n Significant reductions of risk of falling (repeated measures ANOVA F = 8.90, P = 0.008), an increase in muscular strength (ANOVA F = 3.0, P = 0.03), and an increase in activity level (ANOVA F = 3.38, P = 0.02) were found in the experimental group as compared to the control group. Further on, there was 89% reduction of falls reported in the experimental group (experimental pre/post 8/1 falls; control group pre/post 5/6 falls).\n This study provides support for our intervention programme aimed at reducing the risk of falling in elderly participants diagnosed with osteopenia or osteoporosis. The data obtained from the pilot study allow the calculation of the actual sample size needed for a larger randomized trial.",
"To determine whether vitamin D supplementation can reduce the incidence of falls and fractures in older people in residential care who are not classically vitamin D deficient.\n Randomized, placebo-controlled double-blind, trial of 2 years' duration.\n Multicenter study in 60 hostels (assisted living facilities) and 89 nursing homes across Australia.\n Six hundred twenty-five residents (mean age 83.4) with serum 25-hydroxyvitamin D levels between 25 and 90 nmol/L.\n Vitamin D supplementation (ergocalciferol, initially 10,000 IU given once weekly and then 1,000 IU daily) or placebo for 2 years. All subjects received 600 mg of elemental calcium daily as calcium carbonate.\n Falls and fractures recorded prospectively in study diaries by care staff.\n The vitamin D and placebo groups had similar baseline characteristics. In intention-to-treat analysis, the incident rate ratio for falling was 0.73 (95% confidence interval (CI)=0.57-0.95). The odds ratio for ever falling was 0.82 (95% CI=0.59-1.12) and for ever fracturing was 0.69 (95% CI=0.40-1.18). An a priori subgroup analysis of subjects who took at least half the prescribed capsules (n=540), demonstrated an incident rate ratio for falls of 0.63 (95% CI=0.48-0.82), an odds ratio (OR) for ever falling of 0.70 (95% CI=0.50-0.99), and an OR for ever fracturing of 0.68 (95% CI=0.38-1.22).\n Older people in residential care can reduce their incidence of falls if they take a vitamin D supplement for 2 years even if they are not initially classically vitamin D deficient.",
"To determine the effectiveness of vitamin D and home-based quadriceps resistance exercise on reducing falls and improving the physical health of frail older people after hospital discharge.\n Multicenter, randomized, controlled trial with a factorial design.\n Five hospitals in Auckland, New Zealand, and Sydney, Australia.\n Two hundred forty-three frail older people.\n Patients were randomized to receive a single dose of vitamin D (calciferol, 300,000 IU) or placebo tablets and 10 weeks of high-intensity home-based quadriceps resistance exercise or frequency-matched visits.\n The primary endpoints were physical health according to the short-form health survey at 3 months and falls over 6 months. Physical performance and self-rated function were secondary endpoints. Assessments took place in the participants' homes at 3 and 6 months after randomization and were performed by blinded assessors.\n There was no effect of either intervention on physical health or falls, but patients in the exercise group were at increased risk of musculoskeletal injury (risk ratio = 3.6, 95% confidence interval = 1.5-8.0). Vitamin D supplementation did not improve physical performance, even in those who were vitamin D deficient (<12 ng/mL) at baseline.\n Neither vitamin D supplementation nor a home-based program of high-intensity quadriceps resistance exercise improved rehabilitation outcomes in frail older people after hospitalization. There was no effect of vitamin D on physical performance, and the exercises increased the risk of musculoskeletal injury. These findings do not support the routine use of these interventions at these dosages in the rehabilitation of frail older people.",
"The aim of the study was to examine the effects of different interventions that are used to prevent falls. These were education, Tai Chi Chuan and education plus Tai Chi Chuan; the study involved a five-month implantation period and a one-year follow-up period.\n With advancing years, a fall can be very serious and an increased number of falls/re-falls among older adults has been noted. Hence, both education about risk factors and balance exercise programs such as Tai Chi Chuan may help to prevent falls.\n This study adopted a randomised case-controlled design with a two-by-two factorial approach. It included three intervention groups and one control group in a community-based program.\n Cluster-randomised sampling was used and four villages in Taiwan City were selected. Three interventions groups and one control group were involved over five-months from late July 2000-January 2001 and each participant was followed up one year later (n = 163).\n The intervention involving education plus Tai Chi Chuan resulted in a statistically significant reduction in falls and the risk factors of falls over the five-month intervention. After one-year follow-up, participants receiving any one of the interventions showed a reduction in falls compared with the control group.\n Tai Chi Chuan was able to improve gait balance significantly. Education may also help participants to prevent falls-by eliminating related risk factors present in their environment. However, it was found that at the one-year follow-up, any one of the three interventions had reduced falls significantly.\n The prevention of falls among older adults seems to needs multiple interventions. Education plus Tai Chi Chuan has both an immediately and a long-term effect and it is possible that a shorter intervention period using this approach would also be successful.",
"To determine the effect of four vitamin D supplement doses on falls risk in elderly nursing home residents.\n Secondary data analysis of a previously conducted randomized clinical trial.\n Seven hundred twenty-five-bed long-term care facility.\n One hundred twenty-four nursing home residents (average age 89).\n Participants were randomly assigned to receive one of four vitamin D supplement doses (200 IU, 400 IU, 600 IU, or 800 IU) or placebo daily for 5 months.\n Number of fallers and number of falls assessed using facility incident tracking database.\n Over the 5-month study period, the proportion of participants with falls was 44% in the placebo group (11/25), 58% (15/26) in the 200 IU group, 60% (15/25) in the 400 IU group, 60% (15/25) in the 600 IU group, and 20% (5/23) in the 800 IU group. Participants in the 800 IU group had a 72% lower adjusted-incidence rate ratio of falls than those taking placebo over the 5 months (rate ratio=0.28; 95% confidence interval=0.11-0.75). No significant differences were observed for the adjusted fall rates compared to placebo in any of the other supplement groups.\n Nursing home residents in the highest vitamin D group (800 IU) had a lower number of fallers and a lower incidence rate of falls over 5 months than those taking lower doses. Adequate vitamin D supplementation in elderly nursing home residents could reduce the number of falls experienced by this high falls risk group.",
"To determine whether vitamin D supplementation reduces the risk of fracture or falls in elderly people in care home accommodation.\n A randomised controlled trial of cluster design.\n 223 Residential units (mainly identical 30-bedded units), within 118 homes for elderly people throughout Britain, with 3,717 participating residents (76% women, average age 85 years). The units provided mainly or entirely residential care (35% of residents), nursing care (42%) or care for elderly mentally infirm (EMI) residents (23%).\n Participants were randomly allocated by residential unit (cluster design) to a treated group offered ergocalciferol 2.5 mg every 3 months (equivalent to a daily dose of 1,100 IU), or to a control group. Fractures were reported by staff and confirmed in hospital, and routinely collected data on reported falls were obtained.\n After median follow-up of 10 months (interquartile range 7-14 months), 64 (3.6%) of 1,762 vitamin D-treated residents and 51 (2.6%) of 1,955 controls had one or more non-vertebral fractures, and 24 (1.3%) and 20 (1.0%), respectively, had a hip fracture. The proportion reporting at least one fall was 44% in vitamin D-treated and 43% in control residents. The differences between the vitamin D and control groups were not statistically significant. The incidence of all non-vertebral fractures in the care homes (3.2% per year) and of hip fractures (1.1% per year) was low, similar to rates in elderly people in sheltered accommodation, and the pre-treatment serum 25-hydroxy vitamin D concentration was high [median 47 nmol/l, measured in a 1% (n = 18) sample].\n We found no evidence that vitamin D prevents fractures or falls in elderly people in care home accommodation.",
"To examine the effectiveness of cognitive-behavioural strategies with/without intense Tai Chi exercise in reducing fear of falling among community-dwelling elderly adults. Background. Fear of falling is a major health problem among community-dwelling older persons. The prevalence of this fear ranges from 29% to 77%, indicating the importance of developing effective strategies to reduce fear of falling among elderly adults.\n Data were collected from January to December 2007. A randomized controlled trial with three groups (control, cognitive-behavioural and cognitive-behavioural with Tai Chi). Participants were assessed at baseline for demographic data, falls-related history, and fear of falling. Data on these variables plus falls, mobility, social support behaviour and satisfaction, and quality of life were also collected at 2 and 5 months after interventions.\n Participants in the three groups differed significantly in both measures of fear of falling (F = 20·89, P < 0·001; F = 6·09, P < 0·001) and mobility (F = 30·33, P < 0·001), social support behaviour and satisfaction (F = 3·32, P < 0·05 and F = 6·35, P < 0·001, respectively), and quality of life (F = 16·66, P< 0·001). In addition, participants who received the cognitive-behavioural intervention with Tai Chi had significantly lower fear of falling scores (P < 0·001) and higher mobility (P < 0·001), social support satisfaction (P < 0·01) and quality of life (P < 0·001) than the cognitive-behavioural alone and control groups at 5 months. The three groups did not differ significantly in falls.\n The results of this trial suggest that the cognitive-behavioural intervention with Tai Chi exercise helped community-dwelling elderly adults to enhance their mobility, to manage their fear of falling and to increase their quality of life.\n © 2011 Blackwell Publishing Ltd.",
"In 242 community-dwelling seniors, supplementation with either 1000 mg of calcium or 1000 mg of calcium plus vitamin D resulted in a decrease in the number of subjects with first falls of 27% at month 12 and 39% at month 20. Additionally, parameters of muscle function improved significantly.\n The efficacy of vitamin D and calcium supplementation on risk of falling in the elderly is discussed controversially. Randomized controlled trials using falls as primary outcome are needed. We investigated long-term effects of calcium and vitamin D on falls and parameters of muscle function in community-dwelling elderly women and men.\n Our study population consisted of 242 individuals recruited by advertisements and mailing lists (mean [ +/- SD] age, 77 +/- 4 years). All serum 25-hydroxyvitamin D (25[OH]D) levels were below 78 nmol/l. Individuals received in a double blinded fashion either 1000 mg of calcium or 1000 mg of calcium plus 800 IU of vitamin D per day over a treatment period of 12 months, which was followed by a treatment-free but still blinded observation period of 8 months. Falls were documented using diaries. The study took place in Bad Pyrmont, Germany (latitude 52 degrees ) and Graz, Austria (latitude 46 degrees ).\n Compared to calcium mono, supplementation with calcium plus vitamin D resulted in a significant decrease in the number of subjects with first falls of 27% at month 12 (RR = 0.73; CI = 0.54-0.96) and 39% at month 20 (RR = 0.61; CI = 0.34-0.76). Concerning secondary endpoints, we observed significant improvements in quadriceps strength of 8%, a decrease in body sway of 28%, and a decrease in time needed to perform the TUG test of 11%.\n Combined calcium and vitamin D supplementation proved superior to calcium alone in reducing the number of falls and improving muscle function in community-dwelling older individuals.",
"The hypothesis was that the calcium and vitamin D supplementation prevents falls at the population level.Study design: The OSTPRE-FPS was a randomized population-based open-trial with 3-year follow-up. The supplementation group (n=1566) received daily cholecalciferol 800IU+calcium carbonate 1000mg, while the control group (n=1573) received no supplementation or placebo. A randomly selected subsample of 593 subjects underwent a detailed measurement program including serum 25(OH)D measurements.\n The occurrence of falls was the primary outcome of the study. The participants in the subsample were telephoned at 4 months intervals and the rest of the trial population was interviewed by phone once a year.\n In the entire trial population (ETP), there were 812 women with 1832 falls in the intervention group and 833 women with 1944 falls in the control group (risk ratio was 0.98, 95% CI 0.92-1.05, P=0.160). The supplementation was not associated with single or multiple falls in the ETP. However, in the subsample, multiple fall incidence decreased by 30% (odds ratio (OR) 0.70, 95% CI 0.50-0.97, P=0.034) in the supplementation group. Further, the supplementation decreased the incidence of multiple falls requiring medical attention (OR 0.72, 95% CI 0.53-0.97, P=0.031) in the ETP. The mean compliance in the entire trial population was 78% and in the subsample 79%.\n Overall, the primary analysis showed no association between calcium and vitamin D supplementation and risk of falls. However, the results of a post hoc analysis suggested that there was a decreased risk of multiple falls requiring medical attention: this finding requires confirmation.\n Copyright 2009 Elsevier Ireland Ltd. All rights reserved.",
"recent studies have found that moderate intensity exercise is an effective intervention strategy for preventing falls in older people. However, research is required to determine whether supervised group exercise programmes, conducted in community settings with at-risk older people referred by their health care practitioner are also effective in improving physical functioning and preventing falls in this group.\n to determine whether participation in a weekly group exercise programme with ancillary home exercises over one year improves balance, muscle strength, reaction time, physical functioning, health status and prevents falls in at-risk community-dwelling older people.\n the sample comprised 163 people aged over 65 years identified as at risk of falling using a standardised assessment screen by their general practitioner or hospital-based physiotherapist, residing in South Western Sydney, Australia. Subjects were randomised into either an exercise intervention group or a control group. Physical performance and general health measures were assessed at baseline and repeated 6-months into the trial. Falls were measured over a 12-month follow-up period using monthly postal surveys.\n at baseline both groups were well matched in their physical performance, health and activity levels. The intervention subjects attended a median of 23 exercise classes over the year, and most undertook the home exercise sessions at least weekly. At retest, the exercise group performed significantly better than the controls in three of six balance measures; postural sway on the floor with eyes open and eyes closed and coordinated stability. The groups did not differ at retest in measures of strength, reaction time and walking speed or on Short-Form 36, Physical Activity Scale for the Elderly or fear of falling scales. Within the 12-month trial period, the rate of falls in the intervention group was 40% lower than that of the control group (IRR=0.60, 95% CI 0.36-0.99).\n these findings indicate that participation in a weekly group exercise programme with ancillary home exercises can improve balance and reduce the rate of falling in at-risk community dwelling older people.",
"To evaluate the effects of two exercise approaches, Tai Chi (TC) and computerized balance training (BT), on specified primary outcomes (biomedical, functional, and psychosocial indicators of frailty) and secondary outcomes (occurrence of falls).\n The Atlanta FICSIT (Frailty and Injuries: Cooperative Studies of Intervention Techniques), a prospective, randomized, controlled clinical trial with three arms (TC, BT, and education [ED]. Intervention length was 15 weeks, with primary outcomes measured before and after intervention and at 4-month follow-up. Falls were monitored continuously throughout the study.\n Persons aged 70 and older living in the community.\n A total of 200 participants, 162 women and 38 men; mean age was 76.2.\n Biomedical (strength, flexibility, cardiovascular endurance, body composition), functional (IADL), and psychosocial well-being (CES-D scale, fear of falling questionnaire, self-perception of present and future health, mastery index, perceived quality of sleep, and intrusiveness) variables.\n Grip strength declined in all groups, and lower extremity range of motion showed limited but statistically significant changes. Lowered blood pressure before and after a 12-minute walk was seen following TC participation. Fear of falling responses and intrusiveness responses were reduced after the TC intervention compared with the ED group (P = .046 and P = .058, respectively). After adjusting for fall risk factors, TC was found to reduce the risk of multiple falls by 47.5%.\n A moderate TC intervention can impact favorably on defined biomedical and psychosocial indices of frailty. This intervention can also have favorable effects upon the occurrence of falls. Tai Chi warrants further study as an exercise treatment to improve the health of older people.",
"The authors' objective was to evaluate the efficacy of a 6-month Tai Chi intervention for decreasing the number of falls and the risk for falling in older persons.\n This randomized controlled trial involved a sample of 256 physically inactive, community-dwelling adults aged 70 to 92 (mean age, 77.48 years; standard deviation, 4.95 years) who were recruited through a patient database in Portland, Oregon. Participants were randomized to participate in a three-times-per-week Tai Chi group or to a stretching control group for 6 months. The primary outcome measure was the number of falls; the secondary outcome measures included functional balance (Berg Balance Scale, Dynamic Gait Index, Functional Reach, and single-leg standing), physical performance (50-foot speed walk, Up&Go), and fear of falling, assessed at baseline, 3 months, 6 months (intervention termination), and at a 6-month postintervention follow-up.\n At the end of the 6-month intervention, significantly fewer falls (n=38 vs 73; p=.007), lower proportions of fallers (28% vs 46%; p=.01), and fewer injurious falls (7% vs 18%; p=.03) were observed in the Tai Chi group compared with the stretching control group. After adjusting for baseline covariates, the risk for multiple falls in the Tai Chi group was 55% lower than that of the stretching control group (risk ratio,.45; 95% confidence interval, 0.30 to 0.70). Compared with the stretching control participants, the Tai Chi participants showed significant improvements (p<.001) in all measures of functional balance, physical performance, and reduced fear of falling. Intervention gains in these measures were maintained at a 6-month postintervention follow-up in the Tai Chi group.\n A three-times-per-week, 6-month Tai Chi program is effective in decreasing the number of falls, the risk for falling, and the fear of falling, and it improves functional balance and physical performance in physically inactive persons aged 70 years or older.",
"To test the effectiveness of using a full-time project nurse to assist residential aged care facilities in using evidence-based approaches to falls injury prevention.\n Cluster randomised controlled trial involving 5391 residents in 88 aged care facilities in the Hunter and Lower Mid North Coast areas of New South Wales. Residents were followed for 545 days or until death or discharge. Data were collected from July 2005 to June 2007.\n Employment of a project nurse to encourage best-practice falls injury prevention strategies during the 17-month intervention period.\n Monthly data about falls, falls injury and falls injury prevention programs; audit of hospitalisation for fractured neck of femur.\n Despite significant increases in the provision of hip protectors and use of vitamin D supplementation in both intervention and control facilities, there was no difference in the number of falls or falls injuries between the intervention and control groups, nor a reduction in falls overall. There was also no difference between the 7-month pre-intervention period and the intervention period in the number of falls or falls injuries. Factors related to residents having an increased risk of falls with fractured neck of femur included being ambulant, having dementia, increasing age, and having a high falls risk assessment score.\n It is difficult to change falls risk among high-risk populations, including people with dementia. The use of important strategies such as hip protectors and vitamin D and calcium supplementation increased during the study, probably with contamination of control facilities. Longer follow-up may be required to measure the impact on falls outcomes of the strategy of using a facilitating nurse.\n Australian New Zealand Clinical Trials Registry ACTRN12605000540617.",
"To test whether Stepping On, a multifaceted community-based program using a small-group learning environment, is effective in reducing falls in at-risk people living at home.\n A randomized trial with subjects followed for 14 months.\n The interventions were conducted in community venues, with a follow-up home visit.\n Three hundred ten community residents aged 70 and older who had had a fall in the previous 12 months or were concerned about falling.\n The Stepping On program aims to improve fall self-efficacy, encourage behavioral change, and reduce falls. Key aspects of the program are improving lower-limb balance and strength, improving home and community environmental and behavioral safety, encouraging regular visual screening, making adaptations to low vision, and encouraging medication review. Two-hour sessions were conducted weekly for 7 weeks, with a follow-up occupational therapy home visit.\n The primary outcome measure was falls, ascertained using a monthly calendar mailed by each participant.\n The intervention group experienced a 31% reduction in falls (relative risk (RR)=0.69, 95% confidence interval (CI)=0.50-0.96; P=.025). This was a clinically meaningful result demonstrating that the Stepping On program was effective for community-residing elderly people. Secondary analysis of subgroups showed that it was particularly effective for men (n=80; RR=0.32, 95% CI=0.17-0.59).\n The results of this study renew attention to the idea that cognitive-behavioral learning in a small-group environment can reduce falls. Stepping On offers a successful fall-prevention option.\n Copyright 2004 American Geriatrics Society",
"To assess whether a pragmatic multidisciplinary fall-prevention program was more effective than usual care in preventing new falls and functional decline in elderly people.\n A two-group, randomized, controlled trial with 12 months of follow-up.\n University hospital and home-based intervention, the Netherlands.\n Three hundred thirty-three community-dwelling Dutch people aged 65 and over who were seen in an emergency department after a fall.\n Participants in the intervention group underwent a detailed medical and occupational-therapy assessment to evaluate and address risk factors for recurrent falls, followed by recommendations and referral if indicated. People in the control group received usual care.\n Number of people sustaining a fall (fall calendar) and daily functioning (Frenchay Activity Index).\n Results showed no statistically significantly favorable effects on falls (odds ratio=0.86, 95% confidence interval (CI)=0.50-1.49) or daily functioning (regression coefficient=0.37, CI=-0.90 to 1.63) after 12 months of follow-up.\n The multidisciplinary fall-prevention program was not effective in preventing falls and functional decline in this Dutch healthcare setting. Implementing the program in its present form in the Netherlands is not recommended. This trial shows that there can be considerable discrepancy between the \"ideal\" (experimental) version of a program and the implemented version of the same program. The importance of implementation research in assessing feasibility and effectiveness of such a program in a specific healthcare setting is therefore stressed.",
"Osteoporotic fractures in older people are a major and increasing public health problem. We examined the effect of vitamin D supplementation on fracture rate in people living in sheltered accommodation.\n In a pragmatic double blind randomised controlled trial of 3 years duration, we examined 3,440 people (2,624 women and 816 men) living in residential or care home. We used four-monthly oral supplementation using 100,000 IU vitamin D(2) (ergocalciferol). As a main outcome measure, we used the incidence of first fracture using an intention to treat analysis. This was a multicentre study in 314 care homes or sheltered accommodation complexes in South Wales, UK.\n The vitamin D and placebo groups had similar baseline characteristics. In intention-to-treat analysis, 205 first fractures occurred in the intervention group during a total of 2,846 person years of follow-up (7 fractures per 100 people per year of follow-up), with 218 first fractures in the control group over 2,860 person years of follow-up. The hazard ratio of 0.95 (95% confidence interval 0.79-1.15) for intervention compared to control was not statistically significant.\n Supplementation with four-monthly 100,000 IU of oral vitamin D(2) is not sufficient to affect fracture incidence among older people living in institutional care.",
"To test the effectiveness of, and explore interactions between, three interventions to prevent falls among older people.\n A randomised controlled trial with a full factorial design.\n Urban community in Melbourne, Australia.\n 1090 aged 70 years and over and living at home. Most were Australian born and rated their health as good to excellent; just over half lived alone.\n Three interventions (group based exercise, home hazard management, and vision improvement) delivered to eight groups defined by the presence or absence of each intervention.\n Time to first fall ascertained by an 18 month falls calendar and analysed with survival analysis techniques. Changes to targeted risk factors were assessed by using measures of quadriceps strength, balance, vision, and number of hazards in the home.\n The rate ratio for exercise was 0.82 (95% confidence interval 0.70 to 0.97, P=0.02), and a significant effect (P<0.05) was observed for the combinations of interventions that involved exercise. Balance measures improved significantly among the exercise group. Neither home hazard management nor treatment of poor vision showed a significant effect. The strongest effect was observed for all three interventions combined (rate ratio 0.67 (0.51 to 0.88, P=0.004)), producing an estimated 14.0% reduction in the annual fall rate. The number of people needed to be treated to prevent one fall a year ranged from 32 for home hazard management to 7 for all three interventions combined.\n Group based exercise was the most potent single intervention tested, and the reduction in falls among this group seems to have been associated with improved balance. Falls were further reduced by the addition of home hazard management or reduced vision management, or both of these. Cost effectiveness is yet to be examined. These findings are most applicable to Australian born adults aged 70-84 years living at home who rate their health as good.",
"To evaluate the effectiveness of Tai Chi Chuan in fall prevention in elderly people living at home with a high risk of falling.\n Randomized controlled trial.\n Two industrial towns in the western part of the Netherlands.\n Two hundred sixty-nine elderly people (average age 77) living at home with a high risk of falling.\n The intervention group received Tai Chi Chuan training for 1 hour twice a week for 13 weeks; the control group received usual care. Both groups received a brochure containing general information on how to prevent fall incidents.\n Primary outcome was the number of falls over 12 months. Secondary outcomes were balance, fear of falling, blood pressure, heart rate at rest, forced expiratory volume during the first second, peak expiratory flow, physical activity, and functional status.\n After 12 months, no lower fall risk in the Tai Chi Chuan group was observed than in the control group (adjusted hazard ratio=1.16; 95% confidence interval=0.84-1.60), and there were no significant intervention effects on the secondary outcome measures.\n These results suggest that Tai Chi Chuan may not be effective in elderly people at a high risk of falling who live at home.",
"Falls, loss of health-related quality of life and physical capacity, reduced participation in activities of daily living, and increased fear of falling are all potential outcomes for older adults discharged from hospital. A low-cost video based exercise programme may address this.\n This study was a randomized controlled trial with blinded outcomes assessment and a six-month follow-up.\n Participants were older adults (>65 years) using a mobility aid discharged from a tertiary hospital in Brisbane, Australia, without referral for community-based rehabilitation services.\n A digital video disk-based programme encompassing six exercise types each with six levels of difficulty. A home visit from a project physiotherapist was conducted to ensure patient safety. Control group patients received usual care.\n Falls, health-related quality of life, participation in activities of daily living, physical capacity and fear of falling.\n Study participants (n = 53, 19 intervention, 34 control) experienced decreasing health-related quality of life, several falls (72), and lower levels of participation in activities of daily living over the six-month follow-up. The intervention group did not differ significantly from the control group in terms of the outcomes examined, though a non-significant reduction in the rate of falls was observed. Intervention group participants complied with the exercise programme well during the first two weeks following discharge from hospital but then reduced their compliance levels thereafter.\n The intervention may be beneficial for reducing the rate of falls in this patient population though further research with a larger sample size is indicated.",
"This paper reports a study to determine changes in the physical fitness (knee and ankle muscle strength, balance, flexibility, and mobility), fall avoidance efficacy, and fall episodes of institutionalized older adults after participating in a 12-week Sun-style Tai Chi exercise programme.\n Fall prevention has a high priority in health promotion for older people because a fall is associated with serious morbidity in this population. Regular exercise is effective in fall prevention for older adults because of improvements in strength and balance. Tai Chi exercise is considered to offer great potential for health promotion and rehabilitation, particularly in the maintenance of good mental and physical condition in older people.\n A quasi-experimental design with a non-equivalent control group was used. Data were collected from September 2001 to January 2002. A total of 68 fall-prone older adults with a mean age of 77.8 years participated in the study, and 29 people in the Tai Chi group and 30 controls completed the post-test measures. The Tai Chi exercise programme was provided three times a week for 12 weeks in the experimental group. Data were analysed for group differences using t-tests.\n At post-test, the experimental group showed significantly improved muscle strength in knee and ankle flexors (P < 0.001) and extensors (P < 0.01), and improved flexibility (P < 0.01) and mobility (P < 0.001) compared with the control group. There was no significant group difference in fall episodes, but the relative risk ratio for the Tai Chi exercise group compared with the control group was 0.62. The experimental group reported significantly more confidence in fall avoidance than did the control group.\n The findings reveal that Tai Chi exercise programmes can safely improve physical strength and reduce fall risk for fall-prone older adults in residential care facilities.",
"To determine whether a multifactorial falls prevention program reduces falls in people with stroke at risk of recurrent falls and whether this program leads to improvements in gait, balance, strength, and fall-related efficacy.\n A single blind, multicenter, randomized controlled trial with 12-month follow-up.\n Participants were recruited after discharge from rehabilitation and followed up in the community.\n Participants (N=156) were people with stroke at risk of recurrent falls being discharged home from rehabilitation.\n Tailored multifactorial falls prevention program and usual care (n=71) or control (usual care, n=85).\n Primary outcomes were rate of falls and proportion of fallers. Secondary outcomes included injurious falls, falls risk, participation, activity, leg strength, gait speed, balance, and falls efficacy.\n There was no significant difference in fall rate (intervention: 1.89 falls/person-year, control: 1.76 falls/person-year, incidence rate ratio=1.10, P=.74) or the proportion of fallers between the groups (risk ratio=.83, 95% confidence interval=.60-1.14). There was no significant difference in injurious fall rate (intervention: .74 injurious falls/person-year, control: .49 injurious falls/person-year, incidence rate ratio=1.57, P=.25), and there were no significant differences between groups on any other secondary outcome.\n This multifactorial falls prevention program was not effective in reducing falls in people with stroke who are at risk of falls nor was it more effective than usual care in improving gait, balance, and strength in people with stroke. Further research is required to identify effective interventions for this high-risk group.\n Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.",
"To assess the effectiveness of a trained district nurse individually prescribing a home based exercise programme to reduce falls and injuries in elderly people and to estimate the cost effectiveness of the programme.\n Randomised controlled trial with one year's follow up.\n Community health service at a New Zealand hospital.\n 240 women and men aged 75 years and older.\n 121 participants received the exercise programme (exercise group) and 119 received usual care (control group); 90% (211 of 233) completed the trial.\n Number of falls, number of injuries resulting from falls, costs of implementing the programme, and hospital costs as a result of falls.\n Falls were reduced by 46% (incidence rate ratio 0.54, 95% confidence interval 0.32 to 0.90). Five hospital admissions were due to injuries caused by falls in the control group and none in the exercise group. The programme cost $NZ1803 (523 pound sterling) (at 1998 prices) per fall prevented for delivering the programme and $NZ155 per fall prevented when hospital costs averted were considered.\n A home exercise programme, previously shown to be successful when delivered by a physiotherapist, was also effective in reducing falls when delivered by a trained nurse from within a home health service. Serious injuries and hospital admissions due to falls were also reduced. The programme was cost effective in participants aged 80 years and older compared with younger participants.",
"to evaluate a nurse-led management plan and care pathway for older people discharged from an Accident and Emergency Department after a fall.\n randomized controlled trial.\n a large teaching hospital.\n 348 consecutive patients aged 65 or over attending the Accident and Emergency Department with a fall.\n we randomized patients to falls nurse intervention or usual care. Within 4 weeks, the intervention group received a home assessment to address easily modifiable risk factors for falls. This included assessments of medication, ECG, blood pressure, cognition, visual acuity, hearing, vestibular dysfunction, balance, mobility, feet and footwear. All patients were given advice and education about general safety in the home.\n Further falls, functional ability, re-attendance at the Accident and Emergency Department and admission to hospital.\n at 6 months post-Index fall, 36 patients in the intervention group and 39 patients in the control group had had 89 and 145 falls respectively. Although the intervention group had less falls, this was not significant (P>0.05). Similarly, the intervention group had fewer fall-related admissions and bed days (8 and 69 respectively) than the control group (10 and 233 respectively). The intervention group scored significantly higher in indicators of function (P<0.05) and mobility within the community (P<0.02).\n although the differences were not significant, patients in the intervention group had fewer falls, less hospital attendances and spent less time in hospital. Moreover, patients in the intervention group were more functionally independent at 6 months post-Index fall.",
"To assess the effectiveness of a home exercise programme of strength and balance retraining exercises in reducing falls and injuries in elderly women.\n Randomised controlled trial of an individually tailored programme of physical therapy in the home (exercise group, n = 116) compared with the usual care and an equal number of social visits (control group, n = 117).\n 17 general practices in Dunedin, New Zealand.\n Women aged 80 years and older living in the community and registered with a general practice in Dunedin.\n Number of falls and injuries related to falls and time between falls during one year of follow up; changes in muscle strength and balance measures after six months.\n After one year there were 152 falls in the control group and 88 falls in the exercise group. The mean (SD) rate of falls was lower in the exercise than the control group (0.87 (1.29) v 1.34 (1.93) falls per year respectively; difference 0.47; 95% confidence interval 0.04 to 0.90). The relative hazard for the first four falls in the exercise group compared with the control group was 0.68 (0.52 to 0.90). The relative hazard for a first fall with injury in the exercise group compared with the control group was 0.61 (0.39 to 0.97). After six months, balance had improved in the exercise group (difference between groups in change in balance score 0.43 (0.21 to 0.65).\n An individual programme of strength and balance retraining exercises improved physical function and was effective in reducing falls and injuries in women 80 years and older.",
"To determine whether an intense tai chi (TC) exercise program could reduce the risk of falls more than a wellness education (WE) program in older adults meeting criteria for transitioning to frailty.\n Randomized, controlled trial of 48 weeks duration.\n Twenty congregate living facilities in the greater Atlanta area.\n Sample of 291 women and 20 men aged 70 to 97.\n Demographics, time to first fall and all subsequent falls, functional measures, Sickness Impact Profile, Centers for Epidemiologic Studies-Depression Scale, Activities-specific Balance Confidence Scale, Falls Efficacy Scales, and adherence to interventions.\n The risk ratio (RR) of falling was not statistically different in the TC group and the WE group (RR=0.75, 95% confidence interval (CI)=0.52-1.08), P=.13). Over the 48 weeks of intervention, 46% (n=132) of the participants did not fall; the percentage of participants that fell at least once was 47.6% for the TC group and 60.3% for the WE group.\n TC did not reduce the RR of falling in transitionally frail, older adults, but the direction of effect observed in this study, together with positive findings seen previously in more-robust older adults, suggests that TC may be clinically important and should be evaluated further in this high-risk population.",
"To determine whether an individualized falls prevention program comprising exercise, visual, and counseling interventions can reduce physiological falls risk and falls in older people.\n Randomized, controlled trial of 12 months' duration.\n Falls Clinic, Royal North Shore Hospital, Sydney, Australia.\n Six hundred twenty people aged 75 and older recruited from a health insurance company membership database. Interventions: Participants in the extensive intervention group (EIG) received individualized interventions comprising exercise and strategies for maximizing vision and sensation; the minimal intervention group (MIG) received brief advice; and the control group (CG) received no intervention.\n Accidental falls, vision, postural sway, coordinated stability, reaction time, lower limb muscle strength, sit-to-stand performance, and physiological profile assessment (PPA) falls risk scores.\n At the 6-month follow-up, PPA falls risk scores were significantly lower in the EIG than in the CG. EIG subjects assigned to the extensive exercise intervention group showed significant improvements in tests of knee flexion strength and sit-to-stand times but no improvements in balance. EIG subjects assigned to the extensive visual intervention group showed significant improvements in tests of visual acuity and contrast sensitivity. The rate of falls and injurious falls within the trial period were similar in the three groups.\n The individualized intervention program reduced some falls risk factors but did not prevent falls. The lack of an effect on falls may reflect insufficient targeting of the intervention to an at-risk group.",
"Falls are common in elderly people. Possible consequences include serious injuries and the post-fall syndrome, with functional decline and limitation of physical activity. The present randomized controlled study sought to clarify the benefits of a combined long-term and home-based fall prevention program for elderly Japanese women. The subjects were individuals aged over 73 years, living at home in a western suburb of Tokyo, who had attended a comprehensive geriatric health check. Persons with a marked decline in the basic activities of daily living (ADL), hemiplegia, or those missing baseline data were excluded. Fifty-two subjects who expressed a wish to participate in the trial were randomized, 28 to an exercise-intervention group and 24 to a control group. Baseline data for age, handgrip force, walking speed, total serum cholesterol, serum albumin, basic ADL, visual and auditory impairments, self-rated health, and experience of falls did not differ significantly between the two groups. Beginning from June 2000, the intervention group attended a 6-month program of fall-prevention exercise classes aimed at improving leg strength, balance, and walking ability; this was supplemented by a home-based exercise program that focused on leg strength. The control group received only a pamphlet and advice on fall prevention. The average rate of attendance at exercise class was 75.3% (range, 64% to 86%). Participants showed significant improvements in tandem walk and functional reach after the intervention program, with enhanced self confidence. At the 8-month follow-up, the proportion of women with falls was 13.6% (3/22) in the intervention group and 40.9% (9/22) in the control group. At 20 months, the proportion remained unchanged, at 13.6% in the intervention group, but had increased to 54.5% (12/22) in the control group, which showed a statistically significant difference between the two groups (Fisher's exact test; P = 0.0097). The total number of falls during the 20-month follow-up period was 6 in the intervention group and 17 in the control group. We conclude that a moderate exercise intervention program plus a home-based program significantly decreases the incidence of falls in both the short and the long term, contributing to improved health and quality of life in the elderly.\n Copyright 2004 Springer-Verlag",
"to determine the clinical effectiveness of a day hospital-delivered multifactorial falls prevention programme, for community-dwelling older people at high risk of future falls identified through a screening process.\n multicentre randomised controlled trial.\n eight general practices and three day hospitals based in the East Midlands, UK. Participants: three hundred and sixty-four participants, mean age 79 years, with a median of three falls risk factors per person at baseline. Interventions: a day hospital-delivered multifactorial falls prevention programme, consisting of strength and balance training, a medical review and a home hazards assessment. Main outcome measure: rate of falls over 12 months of follow-up, recorded using self-completed monthly diaries.\n one hundred and seventy-two participants in each arm contributed to the primary outcome analysis. The overall falls rate during follow-up was 1.7 falls per person-year in the intervention arm compared with 2.0 falls per person-year in the control arm. The stratum-adjusted incidence rate ratio was 0.86 (95% CI 0.73-1.01), P = 0.08, and 0.73 (95% CI 0.51-1.03), P = 0.07 when adjusted for baseline characteristics. There were no significant differences between the intervention and control arms in any secondary outcomes.\n this trial did not conclusively demonstrate the benefit of a day hospital-delivered multifactorial falls prevention programme, in a population of older people identified as being at high risk of a future fall.",
"Falls occur frequently in older people and strongly affect quality of life. Guidelines recommend multifactorial, targeted fall prevention. We evaluated the effectiveness of a multifactorial intervention in older persons with a high risk of recurrent falls.\n A randomized controlled trial was conducted from April 3, 2005, to July 21, 2008, at the geriatric outpatient clinic of a university hospital and regional general practices in the Netherlands. Of 2015 persons identified, 217 persons aged 65 years or older were selected to participate. They had a high risk of recurrent falls and no cognitive impairment and had visited the emergency department or their family physician after a fall. The geriatric assessment and intervention were aimed at reduction of fall risk factors. Primary outcome measures were time to first and second falls after randomization. Secondary outcome measures were fractures, activities of daily living, quality of life, and physical performance.\n Within 1 year, 55 (51.9%) of the 106 intervention participants and 62 (55.9%) of the 111 usual care (control) participants fell at least once. No significant treatment effect was demonstrated for the time to first fall (hazard ratio, 0.96; 95% confidence interval, 0.67-1.37) or the time to second fall (1.13; 0.71-1.80). Similar results were obtained for secondary outcome measures and for per-protocol analysis. One intervention participant died vs 7 in the control group (hazard ratio, 0.15; 95% confidence interval, 0.02-1.21).\n This multifactorial fall-prevention program does not reduce falls in high-risk, cognitively intact older persons. Trial Registration isrctn.org Identifier: ISRCTN11546541.",
"To evaluate the effect of an intervention by a multidisciplinary team to reduce falls in older people's homes.\n Randomized, controlled trial with follow-up of subjects for 1 year.\n University-affiliated geriatric hospital and older patients' homes.\n Three hundred sixty subjects (mean age +/- standard deviation = 81.5 +/- 6.4) admitted from home to a geriatric hospital and showing functional decline, especially in mobility.\n The participants were randomly assigned to receive a comprehensive geriatric assessment followed by a diagnostic home visit and home intervention or a comprehensive geriatric assessment with recommendations and usual care at home. The home intervention included a diagnostic home visit, assessing the home for environmental hazards, advice about possible changes, offer of facilities for any necessary home modifications, and training in the use of technical and mobility aids. An additional home visit was made after 3 months to reinforce the recommendations. After 12 months of follow-up, a home visit was made to all study participants.\n Number of falls, type of recommended home modifications, and compliance with recommendations.\n After 1 year, there were 163 falls in the intervention group and 204 falls in the control group. The intervention group had 31% fewer falls than the control group (incidence rate ratio (IRR) = 0.69, 95% confidence interval (CI) = 0.51-0.97). The intervention was most effective in a subgroup of participants who reported having had two or more falls during the year before recruitment into the study. In this subgroup, the proportion of frequent fallers and the rate of falls was significantly reduced for the intervention group compared with the control group (21 vs 36 subjects with recurrent falls, P =.009; IRR = 0.63, 95% CI = 0.43-0.94). The compliance rate varied with the type of change recommended from 83% to 33% after 12 months of follow-up.\n Home intervention based on home visits to assess the home for environmental hazards, providing information about possible changes, facilitating any necessary modifications, and training in the use of technical and mobility aids was effective in a selected group of frail older subjects with a history of recurrent falling.",
"To determine the effectiveness of a 16-week community-based tai chi program in reducing falls and improving balance in people aged 60 and older.\n Randomized, controlled trial with waiting list control group.\n Community in Sydney, Australia.\n Seven hundred two relatively healthy community-dwelling people aged 60 and older (mean age 69).\n Sixteen-week program of community-based tai chi classes of 1 hour duration per week.\n Falls during 16 and 24 weeks of follow-up were assessed using a calendar method. Balance was measured at baseline and 16-week follow-up using six balance tests.\n Falls were less frequent in the tai chi group than in the control group. Using Cox regression and time to first fall, the hazard ratio after 16 weeks was 0.72 (95% confidence interval (CI)=0.51-1.01, P=.06), and after 24 weeks it was 0.67 (95% CI=0.49-0.93, P=.02). There was no difference in the percentage of participants who had one or more falls. There were statistically significant differences in changes in balance favoring the tai chi group on five of six balance tests.\n Participation in once per week tai chi classes for 16 weeks can prevent falls in relatively healthy community-dwelling older people.",
"To investigate the effect of a referral-based targeted multifactorial falls prevention intervention on the occurrence of recurrent falls and injuries in older people presenting to an emergency department (ED) after a fall and discharged directly home from the ED.\n Randomized controlled trial. Assessors of outcomes were unaware of group allocation.\n Seven EDs in metropolitan Melbourne, Australia.\n Inclusion criteria were community dwelling, aged 60 and older, presenting to an ED after a fall, and discharged directly home. Exclusion criteria were unable to follow simple instructions or walk independently.\n Targeted referrals to existing community services and health promotion recommendations, based on the falls risk factors found in a baseline assessment.\n Primary outcome measures were falls and resultant injuries occurring over the 12-month follow-up period. Falls and injury data were collected using falls calendars supported by medical record reviews.\n Three hundred sixty-one participants were randomized to the standard care group and 351 to the intervention group. No significant difference was found between the two groups over the 12-month follow-up period in number of fallers (relative risk (RR)=1.11, 95% confidence interval (CI)=0.95-1.31] or number of participants sustaining an injury from a fall (RR=1.06, 95% CI=0.86-1.29).\n This study does not support the use of a referral-based targeted multifactorial intervention program to reduce subsequent falls or fall injuries in older people who present to an ED after a fall.\n © 2010, Copyright the Authors. Journal compilation © 2010, The American Geriatrics Society.",
"Using a randomized controlled trial, we tested the efficacy of a fall prevention intervention to reduce falls among adults in a community-based health promotion program. Adults aged 65 and older within two counties were recruited (control n = 257; intervention n = 286). After 12 months, there was a significant decrease in the number of falls in both groups (odds ratio = 0.45, p < .04), but the time by group membership interaction was not significant (χ(2) = 0.15, p < .69). Multivariate analysis did not find significant differences between the control and intervention groups for physical function as measured by a balance test or a sitting/standing test. Further research is needed on effective methods to deliver multifaceted fall interventions to older adults who are already being served by community health promotion programs.",
"The purpose of this randomized controlled trial was to measure the effectiveness of A Matter of Balance, a small-group based balance program, on muscle strength, gait, balance, and fall risk among older community-dwelling adults at risk for falls. A secondary aim was to measure the effects of the program on actual fall rates over the 3-month study.\n Twenty-three older adults were randomly assigned to either an experimental group that participated in a 12-week small-group based balance program or a control group. Subjects were assessed at baseline and following an intervention using the following outcome measures: lower extremity manual muscle testing (MMT) and range of motion; gait analysis on the GAITRite system; balance parameters on the SMART EquiTest, the Timed Up and Go test, the Berg Balance Scale, and incidence of falls.\n A repeated measures ANOVA revealed that there was a significant interaction between groups over time in the Berg Balance Scale scores, P < or = .05. The experimental group improved over time (48.1 to 52.9/56, respectively), whereas the control group decreased in performance (49.1 to 47.8/56, respectively), P < or = .05. The mean number of falls was significantly less in the experimental group during the intervention compared with the control group (0.09 and 0.50, respectively), P < or = .05.\n A community-based multifactorial intervention including individualized fall risk assessment, exercise, and home assessment appears to safely and effectively reduce the number of falls, resulting in significant improvements in functional balance ability and decreased fall risk.",
"The purpose of this study was to evaluate the effectiveness of a 12-month community-based intervention on falls and risk factors (balance, lower extremity strength, and mobility) in community-living older adults.\n Four hundred fifty-three sedentary adults (65 years old or older) were randomized to either a multifaceted intervention (3 times a week group exercise, 6 hours of fall prevention education, comprehensive falls risk assessment results sent to primary health care provider) or control group (written materials on falls prevention). Primary outcome was fall incidence rates calculated from self-reported falls reported monthly for 12 months. Secondary outcomes were tests of leg strength, balance, and mobility prior to and following the 12-month intervention.\n Twelve-month follow-up was completed on 95% of participants. Intent-to-treat analysis found that the incidence rate of falls was 25% lower among those in the intervention group compared with control group (1.33 vs 1.77 falls/person-year, rate ratio 0.75, 95% confidence interval [CI], 0.52-1.09). This difference was not statistically significant. The risk ratio for any fall was 0.96 (95% CI, 0.82-1.13). Small but significant improvements were found on the Berg Balance Test (adjusted mean difference +1.5 points, 95% CI, 0.8-2.3), the Chair Stand Test (adjusted mean difference +1.2, 95% 0.6-1.9), and the Timed Up and Go Test (adjusted mean difference -0.7, 95% CI, -1.2 to -0.2).\n A community-based multifaceted intervention was effective in improving balance, mobility, and leg strength, all known fall risk factors. Although the incidence of falls was lower, the confidence interval included the possibility of no intervention effect on falls.",
"To evaluate the effectiveness of a personalised home programme of exercises and strategies for repeat fallers with Parkinson's disease (PD).\n Patients with a confirmed diagnosis of idiopathic PD, independently mobile, living at home in the community, experiencing more than one fall in the previous 12 months and with intact gross cognitive function were invited to participate in this randomised controlled trial. Usual care was compared with a personalised 6 week, home based exercise and strategy programme. The primary outcomes were rates of falling at 8 weeks and 6 months. Whether participants had repeat fallen, nearly fallen or experienced injurious falls were also examined. Functional Reach, the Berg Balance Test, PD Self-assessment Scale and the Euro Quol were rated by a blinded assessor.\n Participants were randomised to the exercise (n = 70) and control (n = 72) groups. There was a consistent trend towards lower fall rates in the exercise group at both 8 weeks and 6 months and lower rates of injurious falls needing medical attention at 6 months. Lower rates of repeat near falling were evident for the exercise group at 8 weeks (p = 0.004) and 6 months (p = 0.007). There was a positive effect of exercises at 6 months on Functional Reach (p = 0.009) and quality of life (p = 0.033). No significant differences were found on other secondary outcomes measures.\n There was a trend towards a reduction in fall events and injurious falls with a positive effect of exercises on near falls and quality of life.",
"to evaluate the effectiveness of a multifactorial intervention on incidence of falls in psychogeriatric nursing home patients.\n cluster-randomised controlled 12-month trial.\n psychogeriatric wards in 12 nursing homes in The Netherlands. Participants: psychogeriatric nursing home patients (n = 518). Intervention: a general medical assessment and an additional specific fall risk evaluation tool, applied by a multidisciplinary fall prevention team, resulting in general and individual fall prevention activities. Measurements: falls.\n there were 355 falls in 169.5 patient-years (2.09 falls per patient per year) in the intervention group and 422 falls in 166.3 patient-years (2.54 falls per patient per year) in the control group. Intention-to-treat analysis with adjustment for ward-related and patient-related parameters, and intra-cluster correlation, showed that the intervention group had a significantly lower mean fall incidence rate than the control group (rate ratio = 0.64, 95% CI = 0.43-0.96, P = 0.029). Subgroup analyses showed that fall risk declined further as patients participated longer in the intervention programme.\n the introduction of a structured multifactorial intervention to prevent falls in psychogeriatric nursing home patients significantly reduces the number of falls. This reduction is substantial and of high clinical relevance.",
"Exercise as a falls prevention strategy is more complex with people at risk than with the general population. The Lifestyle approach to reducing Falls through Exercise (LiFE) involves embedding balance and lower limb strength training in habitual daily routines.\n A total of 34 community-residing people aged ≥70 years were randomised either into the LiFE programme or into a no-intervention control group and followed up for six months. Inclusion criteria were two or more falls or an injurious fall in the past year.\n There were 12 falls in the intervention group and 35 in the control group. Therelative risk (RR) analysis demonstrated a significant reduction in falls (RR = 0.23; 0.07-0.83). There were indications that dynamic balance (P = 0.04 at three months) and efficacy beliefs (P = 0.04 at six months) improved for the LiFE programme participants. In general, secondary physical and health status outcomes, which were hypothesised as potential mediators of fall risk, improved minimally and inconsistently.\n LiFE was effective in reducing recurrent falls in this at-risk sample. However, there were minimal changes in secondary measures. The study was feasible in terms of recruitment, randomisation, blinding and data collection. A larger randomised trial is needed to investigate long-term efficacy, mechanisms of benefit and clinical significance of this new intervention.",
"Ergocalciferol (vitamin D(2)) supplementation plays a role in fall prevention, but the effect in patients living in the community in sunny climates remains uncertain. We evaluated the effect of ergocalciferol and calcium citrate supplementation compared with calcium alone on the risk of falls in older women at high risk of falling.\n A 1-year population-based, double-blind, randomized controlled trial of 302 community-dwelling ambulant older women aged 70 to 90 years living in Perth, Australia (latitude, 32 degrees S), with a serum 25-hydroxyvitamin D concentration of less than 24.0 ng/mL and a history of falling in the previous year. Participants were randomized to receive ergocalciferol, 1000 IU/d, or identical placebo (hereinafter, ergocalciferol and control groups, respectively). Both groups received calcium citrate, 1000 mg/d. Fall data were collected every 6 weeks.\n Ergocalciferol therapy reduced the risk of having at least 1 fall over 1 year after adjustment for baseline height, which was significantly different between the 2 groups (ergocalciferol group, 53.0%; control group, 62.9%; odds ratio [OR], 0.61; 95% confidence interval [CI], 0.37-0.99). When those who fell were grouped by the season of first fall or the number of falls they had, ergocalciferol treatment reduced the risk of having the first fall in winter and spring (ergocalciferol group, 25.2%; control group, 35.8%; OR, 0.55; 95% CI, 0.32-0.96) but not in summer and autumn, and reduced the risk of having 1 fall (ergocalciferol group, 21.2%; control group, 33.8%; OR, 0.50; 95% CI, 0.28-0.88) but not multiple falls.\n Patients with a history of falling and vitamin D insufficiency living in sunny climates benefit from ergocalciferol supplementation in addition to calcium, which is associated with a 19% reduction in the relative risk of falling, mostly in winter.",
"To evaluate the outcome of an intervention to reduce hazards in the home on the rate of falls in seniors.\n Randomized controlled trial, with follow-up of subjects for 1 year.\n Community-based study in Perth, Western Australia.\n People age 70 and older.\n One thousand eight hundred seventy-nine subjects were recruited and randomly allocated by household to the intervention and control groups in the ratio 1:2. Because of early withdrawals, 1,737 subjects commenced the study. All members of both groups received a single home visit from a research nurse. Intervention subjects (n = 570) were offered a home hazard assessment, information on hazard reduction, and the installation of safety devices, whereas control subjects (n = 1,167) received no safety devices or information on home hazard reduction.\n Both groups recorded falls on a daily calendar. Reported falls were confirmed by a semistructured telephone interview and were assigned to one of three overlapping categories: all falls, falls inside the home, and falls involving environmental hazards in the home. Analysis was by multivariate modelling of rate ratios and odds ratios for falls, corrected for household clustering, using Poisson regression and logistic regression with robust variance estimation.\n Overall, 86% of study subjects completed the 1 year of follow-up. The intervention was not associated with any significant reduction in falls or fall-related injuries. There was no significant reduction in the intervention group in the incidence rate of falls involving environmental hazards inside the home (adjusted rate ratio, 1.11; 95% CI = 0.82-1.50), or the proportion of the intervention group who fell because of hazards inside the home (adjusted odds ratio, 0.97; 95% CI = 0.74-1.28). No reduction was seen in the rate of all falls (adjusted rate ratio, 1.02; 95% CI = 0.83-1.27) or the rate of falls inside the home (adjusted rate ratio, 1.17; 95% CI = 0.85-1.60). There was no significant reduction in the rate of injurious falls in intervention subjects (adjusted rate ratio, 0.92; 95% CI = 0.73-1.14).\n The intervention failed to achieve a reduction in the occurrence of falls. This was most likely because the intervention strategies had a limited effect on the number of hazards in the homes of intervention subjects. The study provides evidence that a one-time intervention program of education, hazard assessment, and home modification to reduce fall hazards in the homes of healthy older people is not an effective strategy for the prevention of falls in seniors.",
"survivors of hip fracture are at 5- to 10-fold risk of a second hip fracture. There is little consensus about secondary prevention. Many are given calcium and vitamin D, but the evidence supporting this is circumstantial.\n to compare the effects of different calcium and vitamin D supplementation regimens on bone biochemical markers, bone mineral density and rate of falls in elderly women post-hip fracture.\n randomised controlled trial.\n orthogeriatric rehabilitation ward.\n 150 previously independent elderly women, recruited following surgery for hip fracture, were assigned to receive a single injection of 300,000 units of vitamin D(2), injected vitamin D(2) plus 1 g/day oral calcium, 800 units/day oral vitamin D(3) plus 1 g/day calcium, or no treatment. Follow-up was one year, with measurement of 25-hydroxyvitamin D, parathyroid hormone, bone mineral density, and falls.\n mean 25-hydroxyvitamin D increased and mean parathyroid hormone was suppressed in all the actively treated groups, more so in the group receiving combined oral vitamin D and calcium. Twenty per cent of participants injected with vitamin D were deficient in 25-hydroxyvitamin D a year later. Bone mineral density showed small but statistically significant differences of up to 4.6% between actively treated groups and placebo. Relative risk of falling in the groups supplemented with vitamin D was 0.48 (95% CI 0.26-0.90) compared with controls.\n Vitamin D supplementation, either orally or with injected vitamin D, suppresses parathyroid hormone, increases bone mineral density and reduces falls. Effects may be more marked with calcium co-supplementation. The 300,000 units of injected vitamin D may not last a whole year.",
"The aim of this report is to investigate the effects of 8 weeks of intensive Tai Chi Chuan (TCC) training on physiological function and fear of falling (FOF) in the less-robust elderly. Forty-nine community-dwelling elderly, aged 60 or older, were classified randomly into a TCC training or control group. Physical performance measures (including one-leg stance, trunk flexion, and walking speed) and interviews were conducted before and after the intervention. The TCC group showed significant improvements in balance and flexibility, and a reduced FOF, when compared with the control group after the intervention. However, walking speed did not change significantly. The results suggest that a high-frequency, short-term TCC training program can improve balance, flexibility, and increase the confidence of less-robust elderly. These suggest the effectiveness of TCC for intervention as a means to prevent falling among high-risk elderly populations.",
"Randomized controlled trials have shown that a combination of vitamin D and calcium can prevent fragility fractures in the elderly. Whether this effect is attributed to the combination of vitamin D and calcium or to one of these nutrients alone is not known. We studied if an intervention with 10 microg of vitamin D3 per day could prevent hip fracture and other osteoporotic fractures in a double-blinded randomized controlled trial. Residents from 51 nursing homes were allocated randomly to receive 5 ml of ordinary cod liver oil (n = 569) or 5 ml of cod liver oil where vitamin D was removed (n = 575). During the study period of 2 years, fractures and deaths were registered, and the principal analysis was performed on the intention-to-treat basis. Biochemical markers were measured at baseline and after 1 year in a subsample. Forty-seven persons in the control group and 50 persons in the vitamin D group suffered a hip fracture. The corresponding figures for all nonvertebral fractures were 76 persons (control group) and 69 persons (vitamin D group). There was no difference in the incidence of hip fracture (p = 0.66, log-rank test), or in the incidence of all nonvertebral fractures (p = 0.60, log-rank test) in the vitamin D group compared with the control group. Compared with the control group, persons in the vitamin D group increased their serum 25-hydroxyvitamin D concentration with 22 nmol/liter (p = 0.001). In conclusion, we found that an intervention with 10 microg of vitamin D3 alone produced no fracture-preventing effect in a nursing home population of frail elderly people.",
"To compare the effect of two modes of delivering a falls prevention service in reducing the rate of falls and improving quality of life, activity levels, and physical status among older adults with a history of recent falls.\n A randomized controlled trial was conducted with a total of 107 participants with blinded baseline and follow-up assessments. The participants were older community-dwelling adults referred for a falls prevention service located in Brisbane, Australia. The intervention was a multiple component falls prevention service delivered in either in a domiciliary or center-based mode of delivery. Both programs were similar apart from setting and consisted of three components, a balance and strength component, falls prevention education, and functional tasks. Physical and psychosocial assessments were administered at baseline, 8-week follow-up and 6-month follow-up. Falls data were collected by monthly telephone contact and by interview at 8 weeks and 6 months.\n The center-based service demonstrated significantly better results in preventing falls over the home-based service. Clients in the center-based arm of the trial experienced fewer total falls and this group also had a greater reduction in the total number of fallers after the intervention.\n This research demonstrates that delivering a similar service in different settings-home based or center based-impacts upon the effectiveness of the service. Community-dwelling older adults with a history of falls should be provided with center-based programs in preference to home-based programs where they are available.",
"falls are the leading causes of accidental death and fragility fractures in older adults. Interventions that assess and reduce falls risk are underutilised.\n to evaluate the impact of a multifaceted community-based programme aimed at optimising evidence-based management of patients at risk for fall-related fractures.\n this was a randomised trial performed from 2003 to 2006.\n community-based intervention in Ontario, Canada.\n eligible patients were community-dwelling, aged > or =55 years and identified to be at risk for fall-related fractures. A total of 201 patients were allocated to the intervention group or to usual care.\n components of the intervention included assessment of falls risk, functional status and home environment, and patient education.\n primary outcome was the implementation of appropriate falls risk assessment at 6 months. Secondary outcomes included falls and fractures at 6 and 12 months.\n the mean age of participants was 72 years, and 41% had fallen with injury in the previous year. Compared to usual care, the intervention increased the number of referrals made to physiotherapy [21% (21/101) vs 6.0% (6/100); relative risk (RR) 3.47, 95% confidence interval (CI) 1.46-8.22] and occupational therapy [15% (15/101) vs 0%; RR 30.7, 95% CI 1.86 to >500]. At 12 months, the number of falls in the intervention group was greater than in the usual care group [23% (23/101) vs 11% (11/100); RR 2.07, 95% CI 1.07-4.02].\n compared to usual care, a multi-faceted intervention increased referrals to physiotherapy and occupational therapy but did not reduce risk of falls. Similar falls reduction interventions cannot be recommended based on the results of this study.",
"To use two different exercise programs over a 2-year period to reduce falls and their sequelae among residents of two long-term care facilities.\n Randomized, controlled trial.\n The study took place at two long-term care facilities with services ranging from independent living to skilled nursing.\n One hundred and ten participants whose average age was 84 and who were capable of ambulating with or without assistive devices and could follow simple directions.\n Participants were randomized to one of two exercise groups (resistance/endurance plus basic enhanced programming or tai chi plus basic enhanced programming) or to a control group (basic enhanced programming only). Exercise classes were held three times per week throughout the study.\n Participants were evaluated for cognitive and physical functioning at baseline and 6, 12, and 24 months. Falls were determined from incident reports filed by the nursing staffs at the facilities.\n Time to first fall, time to death, number of days hospitalized, and incidence of falls did not differ among the treatment and control groups (P>.05). Among all participants, those who fell had significantly lower baseline Folstein Mini-Mental State Examination and instrumental activities of daily living scores and experienced significantly greater declines in these measures over the 2-year program.\n There were no significant differences in falls among the two exercise groups and the control group. Lack of treatment differences and low adherence rates suggest that residents of long-term care facilities may require individualized exercise interventions that can be adapted to their changing needs.",
"to determine the effect of risk factor modification and balance exercise on falls rates in residential care homes.\n cluster randomised controlled trial.\n 196 residents (aged 60 years or over) in 20 residential care homes were enrolled (38% response rate). Homes were randomly allocated to intervention and control arms. A total of 102 residents were consigned to the intervention arm and 94 to the control arm.\n a multifactorial falls prevention programme including 3 months gait and balance training, medication review, podiatry and optometry.\n number of falls/recurrent falls per person, number of medications per person, and change in Tinetti gait and balance measure.\n in the intervention group there was a mean of 2.2 falls per resident per year compared with 4.0 in the control group; this failed to reach statistical significance (P = 0.2) once the intra-cluster correlation (ICC, 0.10) had been accounted for. Several risk factors were reduced in the intervention arm.\n falls risk factor reduction is possible in residents of care homes. A modest reduction in falls rates was demonstrated but this failed to reach statistical significance.",
"Evidence-based guidelines recommend a range of treatments for falls and injury prevention. We undertook a randomised trial of a falls prevention service to screen for falls risk factors and recommend to GPs an evidenced base prescription for falls prevention.\n All patients who presented with a fall to the Emergency Department at Flinders Medical Centre over a 22-week period were considered for the study. We excluded patients with dementia, resident in high care or those transferred to other hospitals and outside our catchment area. Of those who consented, we randomised patients between usual care or to an intervention consisting of a falls risk assessment and writing of an evidence-based prescription faxed to their GP for action. Patients were followed for six months and uptake of advice and fall rates were monitored.\n Four hundred and fifty patients presented with a fall-related attendance and of these 261 patients were eligible for inclusion in the trial. Of these 261 patients, 140 consented and were enrolled in the trial. Over the six months patients in the intervention group were more likely to uptake preventative advice (OR=12.3; 95%CI=4.2-35.9). We were unable to show a reduction in falls (OR= 1.7; 95%CI=0.7-4.4).\n A patient centered evidence-based approach is feasible and effective in increasing uptake of falls prevention advice. Long term compliance with advice needs further exploration.",
"To compare the effectiveness of unsupervised home and supervised group exercise on parameters related to risk of falling among older adults.\n Prospective, single-blind, randomized and controlled trial.\n Nursing home.\n The subjects were selected from 535 independent individuals who resided in a nursing home. Forty-two older adults, aged > 65 years, with risk of falling were recruited, and 32 of them completed the study.\n The 42 subjects were divided into two groups (unsupervised home exercise and supervised exercise group) randomly. Exercise sessions were performed three times a week for a period of eight weeks.\n Measurements were taken at baseline and after the completion of the exercise programme. The fear of falling was evaluated using a visual analogue scale, quadriceps muscle strength was measured with a dynamometer, flexibility was assessed with the sit and reach test, functional mobility was determined using the Timed Up and Go Test, balance was evaluated using one-leg and tandem standing, and Berg Balance Scale and proprioception was assessed with knee position sense.\n Thirty-two subjects (unsupervised home exercise n = 15, supervised group exercise n = 17) completed the exercise programme and all of the measurements. The unsupervised home exercise group showed significant improvement in balance, functional mobility and flexibility (P > 0.05). In addition to balance, functional mobility and flexibility, the supervised exercise group also showed significant improvements in both strength and proprioception (P > 0.05).\n Supervised group exercise is more effective at reducing the risk factors related to falling among older adults living in a nursing home than is unsupervised home exercise.",
"Falls are particularly common among older people living in residential care facilities. The aim of this randomized controlled trial was to evaluate the effectiveness of a high-intensity functional exercise program in reducing falls in residential care facilities.\n Participants comprised 191 older people, 139 women and 52 men, who were dependent in activities of daily living. Their mean+/-SD score on the Mini-Mental State Examination was 17.8+/-5.1 (range 10-30). Participants were randomized to a high-intensity functional exercise program or a control activity, consisting of 29 sessions over 3 months. The fall rate and proportion of participants sustaining a fall were the outcome measures, subsequently analysed using negative binominal analysis and logistic regression analysis, respectively.\n During the 6-month follow-up period, when all participants were compared, no statistically significant differences between groups were found for fall rate (exercise group 3.6 falls per person years [PY], control group 4.6 falls per PY), incidence rate ratio (95% CI) 0.82 (0.49-1.39), p=0.46, or the proportion of participants sustaining a fall (exercise 53%, control 51%), odds ratio (95% CI) 0.95 (0.52-1.74), p=0.86. A subgroup interaction analysis revealed that, among participants who improved their balance during the intervention period, the exercise group had a lower fall rate than the control group (exercise 2.7 falls per PY, control 5.9 falls per PY), incidence rate ratio (95% CI) 0.44 (0.21-0.91), p=0.03.\n In older people living in residential care facilities, a high-intensity functional exercise program may prevent falls among those who improve their balance.",
"Falls are a major cause of morbidity in old age. A small number of fall prevention trials in cognitively intact community-dwelling older people have been effective. This study set out to examine the preventability of falls in older people living in institutional care.\n To evaluate the effectiveness of falls risk factor assessment/modification and seated balance exercise training in reducing falls among elderly people living in residential care.\n 133 residents with a mean age of 84+/- (SD) 6.8 years were allocated at random by home to receive either a 6-month falls risk factor assessment/modification and seated balance exercise training programme (n = 77) or 6 months of reminiscence therapy (n = 56). The risk factors targeted were postural hypotension, polypharmacy, visual acuity, and ambient lighting levels. Falls risk factor assessments and recommendation for modifications were performed at baseline in the intervention group and assessments repeated at 6 months. Functional reach, reaction time, timed up-and- go, grip strength, spinal flexibility, and Philadelphia Geriatric Centre Morale Scale and Mini-Mental State Examination scores were determined at baseline and at 6 months by a 'blind' observer. Falls and fractures were then monitored in both groups during a 7- to 12-month falls-monitoring follow-up period.\n Only 90 of 133 (67.7%) residents completed the 6-month intervention period, and 84 (63.2%) completed the 7- to 12-month falls-monitoring follow-up period. Both prevalence of postural hypotension (p = 0.0005) and poor visual acuity (p = 0.04) were reduced in the intervention group. There was no difference between the groups in the number of falls sustained, the risk of falling [odds ratio 0.45 (95% CI 0.19-1.14)], or in the risk of recurrent falling [odds ratio 1.07 (95% CI 0.40-2.97)]. No significant differences were found between the groups with regard to change in other outcome measures.\n The high drop-out rate reduced the power of this study to detect any effect of the interventions used. It is possible that either the exercises were not sufficiently vigorous or that to improve balance exercises must be performed standing. Further research is required to identify effective fall prevention strategies for elderly people in residential settings.\n Copyright 2000 S. Karger AG, Basel",
"Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures; however, adherence to daily supplementation is typically poor.\n To determine whether a single annual dose of 500,000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture.\n A double-blind, placebo-controlled trial of 2256 community-dwelling women, aged 70 years or older, considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were randomly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years. The study concluded in 2008.\n 500,000 IU of cholecalciferol or placebo.\n Falls and fractures were ascertained using monthly calendars; details were confirmed by telephone interview. Fractures were radiologically confirmed. In a substudy, 137 randomly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels.\n Women in the cholecalciferol (vitamin D) group had 171 fractures vs 135 in the placebo group; 837 women in the vitamin D group fell 2892 times (rate, 83.4 per 100 person-years) while 769 women in the placebo group fell 2512 times (rate, 72.7 per 100 person-years; incidence rate ratio [RR], 1.15; 95% confidence interval [CI], 1.02-1.30; P = .03). The incidence RR for fracture in the vitamin D group was 1.26 (95% CI, 1.00-1.59; P = .047) vs the placebo group (rates per 100 person-years, 4.9 vitamin D vs 3.9 placebo). A temporal pattern was observed in a post hoc analysis of falls. The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months (test for homogeneity; P = .02). In the substudy, the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3% of the substudy participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group, 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L, were approximately 90 nmol/L at 3 months, and remained higher than the placebo group 12 months after dosing.\n Among older community-dwelling women, annual oral administration of high-dose cholecalciferol resulted in an increased risk of falls and fractures.\n anzctr.org.au Identifier: ACTRN12605000658617; isrctn.org Identifier: ISRCTN83409867.",
"This article is a report of a randomized controlled trial to examine the effectiveness of a targeted multiple intervention strategy in reducing the number of patient falls in an acute care hospital.\n Prevention of patient falls remains a challenge that has eluded healthcare institutions. The effectiveness of targeted multiple fall prevention interventions in reducing the incidences of falling has not been established.\n Patients who scored 5 and above on the Hendrich II Fall Risk Model, a fall assessment tool, were recruited in 2006. Patients who were randomized to the intervention group received targeted multiple interventions. Both the research groups received the standard fall prevention interventions from the ward nurses. The rates of fall incidences for both groups were reported with 95% CI, calculated using Wilson method and compared using the Chi-square test. The relative risk was estimated and 95% CI was calculated using the methods described by Armitage and Berry. The times to first fall events were constructed using the Kaplan-Meier method. The hazard ratio was reported at 95% CI and the comparison was made using the log-rank test.\n There were 912 and 910 participants in the control and intervention groups, respectively. The fall incidence rates were 1·5% (95% CI: 0·9-2·6) and 0·4% (95% CI: 0·2-1·1) in the control and intervention groups, respectively. The relative risk estimate of 0·29 (95% CI: 0·1-0·87) favours the intervention group.\n This study showed that targeted multiple interventions were effective in reducing the incidences of falls in patients in the acute care setting.\n © 2011 Blackwell Publishing Ltd.",
"Since falling is associated with serious morbidity among elderly people, we investigated whether the risk of falling could be reduced by modifying known risk factors.\n We studied 301 men and women living in the community who were at least 70 years of age and who had at least one of the following risk factors for falling: postural hypotension; use of sedatives; use of at least four prescription medications; and impairment in arm or leg strength or range of motion, balance, ability to move safely from bed to chair or to the bathtub or toilet (transfer skills), or gait. These subjects were given either a combination of adjustment in their medications, behavioral instructions, and exercise programs aimed at modifying their risk factors (intervention group, 153 subjects) or usual health care plus social visits (control group, 148 subjects).\n During one year of follow-up, 35 percent of the intervention group fell, as compared with 47 percent of the control group (P = 0.04). The adjusted incidence-rate ratio for falling in the intervention group as compared with the control group was 0.69 (95 percent confidence interval, 0.52 to 0.90). Among the subjects who had a particular risk factor at base line, a smaller percentage of those in the intervention group than of those in the control group still had the risk factor at the time of reassessment, as follows: at least four prescription medications, 63 percent versus 86 percent, P = 0.009; balance impairment, 21 percent versus 46 percent, P = 0.001; impairment in toilet-transfer skills, 49 percent versus 65 percent, P = 0.05; and gait impairment, 45 percent versus 62 percent, P = 0.07.\n The multiple-risk-factor intervention strategy resulted in a significant reduction in the risk of falling among elderly persons in the community. In addition, the proportion of persons who had the targeted risk factors for falling was reduced in the intervention group, as compared with the control group. Thus, risk-factor modification may partially explain the reduction in the risk of falling.",
"The purpose of this research was to examine the effect of a multifactorial intervention to prevent falls by increasing self-efficacy to prevent falls, improving the knowledge of medication safety, and decreasing the number of environmental risks in older persons dwelling in the community. A sample of 120 cognitively intact residents of this community who were 65 years of age and older were recruited into a two-group pretest-post-test experimental design and randomly assigned to an experimental group and a comparison group (60 in each group). The intervention was delivered, and data were collected during three home visits in a 4-month period. (1) Experimental subjects improved their fall self-efficacy, environmental safety, and knowledge of medication safety significantly (p < 0.01) as compared with those in the comparison group at post-test; (2) the incidence of falls was reduced at post-test in both groups compared to pretest scores, and the falling was more serious in the comparison group at post-test compared to that in the experimental group. The results can help community health professionals to individualize their interventions to the specific needs of the elderly, thus helping to prevent falls among community-dwelling elders.",
"A randomized trial of falls prevention program that addressed home safety, exercise, and behavioral risks was conducted with 3,182 independently living HMO members age 65 and older. The intervention decreased the odds of falling by 0.85, but only reduced the average number of falls among those who fell by 7%. The effect was strongest among men age 75 and older. The likelihood of avoiding falls requiring medical treatment was not significantly affected by the intervention. We conclude that the intervention dose was not of sufficient intensity or duration to have a marked protective effect on older persons. Future research should focus on more intensive intervention approaches because serious falls do not appear to be amendable to low-intensity environment/behavioral efforts.",
"To assess whether a multifactorial fall prevention program was more effective than usual geriatric care in preventing falls and reducing fear of falling in frail community-dwelling older fallers, with and without cognitive impairment, and in alleviating subjective caregiver burden in caregivers.\n A randomized, 2 parallel-group, single-blind, multicenter trial conducted in 36 pairs of frail fallers, who were referred to a geriatric outpatient clinic after at least 1 fall in the past 6 months, and their informal caregivers.\n Groups of 5 pairs of patients and caregivers received 10 twice-weekly, 2-hour sessions with physical and psychological components and a booster session.\n The primary outcome was the fall rate during a 6-month follow-up. Additionally, we measured fear of falling and subjective caregiver burden. Data on the secondary outcome measures were collected at baseline, directly after, and at 3 and 6 months after the last session of the intervention.\n Directly after the intervention and at the long-term evaluation, the rate of falls in the intervention group was higher than in the control group, although these differences were not statistically significant (RR = 7.97, P = .07 and RR = 2.12, P = .25, respectively). Fear of falling was higher in the intervention group, and subjective caregiver burden did not differ between groups.\n Although we meticulously developed this pairwise multifactorial fall prevention program, it was not effective in reducing the fall rate or fear of falling and was not feasible for caregivers, as compared with regular geriatric care. Future research initiatives should be aimed at how to implement the evidence-based principles of geriatric fall prevention for all frail fallers rather than developing more complex interventions for the frailest.\n Copyright © 2011 American Medical Directors Association. Published by Elsevier Inc. All rights reserved.",
"To compare the adherence to and effectiveness of Tai Chi exercise program through a live, interactive, telecommunication-based exercise (Tele-ex) with that of a similar program through a community center-based exercise (Comm-ex) and a home video-based exercise (Home-ex) among community-dwelling elders who are at risk for falls.\n Three groups randomized controlled trial with pretests and posttests.\n Exercise programs were community-based, and the outcome measures were laboratory-based.\n Adults (N=64) age 65+ years with positive fall history in the previous year and/or significant fear of falling.\n A 24-form, Yang-style Tai Chi for 15 weeks, 3 hours a week.\n Exercise compliance, number of falls, fear of falling (Activities-specific Balance Confidence [ABC] score), self-perceived health (Medical Outcomes Study 36-Item Short Form Health Survey [SF-36]), Timed Up & Go (TUG), single leg stance (SLS), and body sway during quiet stance (medial-lateral foot center of pressure [ML-COP]).\n Tele-ex and Comm-ex groups demonstrated significantly higher exercise attendance and in-class practice time than the Home-ex group (P<.01) and significant reductions in the mean number of falls and injurious falls (P<.01). There were significant improvements posttraining in SLS, ABC, ML-COP, and Physical Health subscore of the SF-36 (P<.05). Both Tele-ex and Comm-ex groups demonstrated larger improvements than the Home-ex group in TUG, ML-COP, and the Social Function, Mental Health, and Physical Health subscores of the MOS SF-36.\n Compared with the Home-ex, the Tele-ex and Comm-ex groups are better in exercise compliance, fall reduction and balance and health improvements. Tele-ex is an effective, affordable, and acceptable choice of exercise for elders.\n Copyright 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.",
"It is important to determine the effect of adherence to a tai chi program on falls and related functional outcomes in older people. This study examined the effect of a community-based tai chi program on injurious falls, balance, gait, and fear of falling among people aged 65 years and older in Taiwan.\n In 6 rural villages in Taichung County, 1,200 subjects participated in the initial assessment. During a 1-year intervention period, all study villages were provided with education on fall prevention. Two villages had been provided tai chi exercise (n=472 participants or \"tai chi villagers\"), and 4 villages served as control villages (n=728 participants or \"control villagers\"). Injurious falls were ascertained by telephone interviews every 3 months over a 2-year study period; additionally, balance, gait, and fear of falling were assessed in 2 follow-up assessments.\n Eighty-eight subjects, 83 from the tai chi villages and 5 from the control villages, participated and practiced in the tai chi program (the group labeled \"tai chi practitioners\"). After the tai chi program, injurious falls among the control villagers significantly declined by 44% (adjusted rate ratio [RR]=0.56; 95% confidence interval [CI]=0.36-0.92). Compared with the results for the control villagers, the decline was 31% greater (RR=0.69; 95% CI=0.30-1.56) among the tai chi villagers and 50% greater (RR=0.5; 95% CI=0.11-2.17) among the tai chi practitioners; the results did not reach statistical significance. Furthermore, compared with the scores for the control villagers, the scores for the tai chi practitioners increased by 1.8 points (95% CI=0.2-3.4) on the Tinetti Balance Scale and increased by 0.9 point (95% CI=0.1-1.8) on the Tinetti Gait Scale. No significant changes in the fear of falling were detected among the tai chi practitioners, tai chi villagers, and control villagers.\n Tai chi can prevent a decline in functional balance and gait among older people. However, the reduction in injurious falls attained with tai chi did not reach statistical significance; the statistical inefficiency may have resulted partly from the large decline in injurious falls in control villagers. Finally, the unexpected effect of educational intervention on reducing injurious falls in different settings needs to be further examined.",
"Among elderly persons, falls account for 87% of all fractures and are contributing factors in many nursing home admissions. This study evaluated the effect of an easily implemented, low-intensity exercise program on the incidence of falls and the time to first fall among a clinically defined population of elderly men and women.\n This community-based, randomized trial compared the exercise intervention with a no-intervention control. The participants were 294 men and women, aged 60 years or older, who had either a hospital admission or bed rest for 2 days or more within the previous month. Exercise participants were scheduled to attend exercise sessions lasting 45 minutes, including warm-up and cool-down, 3 times a week for 8 weeks (24 sessions). Assessments included gait and balance measures, self-reported physical function, the number of medications being taking at baseline, participant age, sex, and history of falling. Falls were tracked for 1 year after each participant's baseline assessment.\n 29% of the study participants reported a fall during the study period. The effect of exercise in preventing falls varied significantly by baseline physical function level (p < or =.002). The risk for falls decreased for exercise participants with low baseline physical functioning (hazard ratio,.51) but increased for exercise participants with high baseline physical functioning (hazard ratio, 3.51).\n This easily implemented, low-intensity exercise program appears to reduce the risk for falls among elderly men and women recovering from recent hospitalizations, bed rest, or both who have low levels of physical functioning.",
"To evaluate the effects of a multifactorial fall prevention program on falls and to identify the subgroups that benefit the most.\n Randomized controlled trial.\n Community-dwelling subjects who had fallen at least once during the previous 12 months.\n Five hundred ninety-one subjects randomized into intervention (IG) (n=293) and control (CG) (n=298) groups.\n A multifactorial 12-month fall prevention program.\n Incidence of falls.\n The intervention did not reduce the incidence of falls overall (incidence rate ratio (IRR) for IG vs CG=0.92, 95% confidence interval (CI)=0.72-1.19). In subgroup analyses, significant interactions between subgroups and groups (IG and CG) were found for depressive symptoms (P=.006), number of falls during the previous 12 months (P=.003), and self-perceived risk of falling (P=.045). The incidence of falls decreased in subjects with a higher number of depressive symptoms (IRR=0.50, 95% CI=0.28-0.88), whereas it increased in those with a lower number of depressive symptoms (IRR=1.20, 95% CI=0.92-1.57). The incidence of falls decreased also in those with at least three previous falls (IRR=0.59, 95% CI=0.38-0.91) compared to those with one or two previous falls (IRR=1.28, 95% CI=0.95-1.72). The intervention was also more effective in subjects with high self-perceived risk of falling (IRR=0.77, 95% CI=0.55-1.06) than in those with low self-perceived risk (IRR=1.28, 95% CI=0.88-1.86).\n The program was not effective in reducing falls in the total sample of community-dwelling subjects with a history of falling, but the incidence of falls decreased in participants with a higher number of depressive symptoms and in those with at least three falls.",
"older people participate in exercise programmes to reduce the risk of falls but no study has investigated a specific balance strategy training intervention presented in a workstation format for small groups.\n to determine whether a specific balance strategy training programmeme delivered in a workstation format was superior to a community based exercise class programme for reducing falls.\n a randomised controlled trial model.\n Neurological Disorders, Ageing and Balance Clinic, Department of Physiotherapy, The University of Queensland.\n 73 males and females over 60 years, living independently in the community and who had fallen in the previous year were recruited.\n all subjects received a falls risk education booklet and completed an incident calendar for the duration of the study. Treatment sessions were once a week for 10 weeks. Subject assessment before and after intervention and at 3 months follow-up included number of falls, co-morbidities, medications, community services and activity level, functional motor ability, clinical and laboratory balance measures and fear of falling.\n all participants significantly reduced the number of falls (P < 0.000). The specific balance strategy intervention group showed significantly more improvement in functional measures than the control group (P = 0.034). Separate group analyses indicated significantly improved performance in functional motor ability and most clinical balance measures for the balance group (P < 0.04). The control group only improved in TUG and TUGcog.\n the results provide evidence that all participants achieved a significant reduction in falls. Specific balance strategy training using workstations is superior to traditional exercise classes for improving function and balance.",
"To test the efficacy of a multicomponent intervention to reduce functional difficulties, fear of falling, and home hazards and enhance self-efficacy and adaptive coping in older adults with chronic conditions.\n A prospective, two-group, randomized trial. Participants were randomized to a treatment group or no-treatment group.\n Urban community-living older people.\n Three hundred nineteen community-living adults aged 70 and older who reported difficulty with one or more activities of daily living.\n Occupational and physical therapy sessions involving home modifications and training in their use; instruction in strategies of problem-solving, energy conservation, safe performance, and fall recovery techniques; and balance and muscle strength training.\n Outcome measures included self-rated functional difficulties with ambulation, instrumental activities of daily living, activities of daily living, fear of falling, confidence performing daily tasks, and use of adaptive strategies. Observations of home hazards were also conducted.\n At 6 months, intervention participants had less difficulty than controls with instrumental activities of daily living (P=.04, 95% confidence interval (CI)=-0.28-0.00) and activities of daily living (P=.03, 95% CI=-0.24 to -0.01), with largest reductions in bathing (P=.02, 95% CI=-0.52 to -0.06) and toileting (P=.049, 95% CI=-0.35-0.00). They also had greater self-efficacy (P=.03, 95% CI=0.02-0.27), less fear of falling (P=.001, 95% CI=0.26-0.96), fewer home hazards (P=.05, 95% CI=-3.06-0.00), and greater use of adaptive strategies (P=.009, 95% CI=0.03-0.22). Benefits were sustained at 12 months for most outcomes.\n A multicomponent intervention targeting modifiable environmental and behavioral factors results in life quality improvements in community-dwelling older people who had functional difficulties, with most benefits retained over a year.",
"To evaluate the effect of multifactorial fall prevention in community-dwelling people aged 65 and older in Denmark.\n Randomized, controlled clinical trial.\n Geriatric outpatient clinic at Glostrup University Hospital.\n Three hundred ninety-two elderly people, mean age 74, 73.7%women, who had visited the emergency department or had been hospitalized due to a fall.\n Identification of general medical, cardiovascular, and physical risk factors for falls and individual intervention in the intervention group. Participants in the control group received usual care.\n Falls were registered prospectively in falls diaries, with monthly telephone calls for collection of data. Outcomes were fall rates and proportion of participants with falls, frequent falls, and injurious falls in 12 months.\n Groups were comparable at baseline. Followup exceeded 90.0%. A total of 422 falls were registered in the intervention group, 398 in the control group. Intention-to-treat analysis revealed no effect of the intervention on fall rates (relative risk=1.06, 95%confidence interval (CI)=0.75 -1.51), proportion with falls (odds ratio (OR)=1.20, 95% CI 0.81-1.79), frequent falls (OR=0.97, 95% CI=0.60-1.56), or injurious falls (OR=0.97, 95% CI=0.57-1.62).\n A program of multifactorial fall prevention aimed at elderly Danish people experiencing at least one injurious fall was not effective in preventing further falls.",
"Long-term vitamin D and calcium supplementation is effective in reducing nonvertebral fractures in elderly people. Increased bone fragility caused by secondary hyperparathyroidism (sHPT) and impaired balance are known risk factors for hip fractures. The hypothesis is that short-term therapy with calcium and vitamin D may improve body sway as well as sHPT more effectively than calcium monotherapy. The effects of 8 weeks of supplementation with vitamin D (cholecalciferol) and calcium on body sway and biochemical measures of bone metabolism were measured. The sample consisted of 148 women (mean [+/-SD] age, 74 +/- 1 years) with a 25-hydroxycholecalciferol level below 50 nmol/liter. They received either 1200 mg of calcium plus 800 IU of vitamin D or 1200 mg of calcium per day. We measured intact parathyroid hormone (PTH), markers of bone turnover, and body sway before and after treatment. Falls and fractures among the participants were followed over a 1-year period. Compared with calcium mono, supplementation with vitamin D and calcium resulted in an increase in serum 25-hydroxyvitamin D of 72% (p < 0.0001), a decrease in the serum PTH of 18% ( p = 0.0432), and a decrease in body sway of 9% (p = 0.0435). The mean number of falls per subject during a 1-year follow-up period was 0.45 for the calcium mono group and 0.24 for the calcium and vitamin D group (p = 0.0346). Short-term supplementation with vitamin D and calcium improves sHPT and body sway and therefore may prevent falls and subsequent nonvertebral fractures in elderly women.",
"Low trauma fractures in older people incur enormous physical, social and economic costs. Previous research indicates that an annual intramuscular injection of vitamin D may reduce fracture rates in this group. This strategy requires validation in a population setting.\n Randomized, double-blind, placebo-controlled trial of 300,000 IU intramuscular (i.m.) vitamin D2 (ergocalciferol) injection or matching placebo every autumn over 3 years. 9440 people (4354 men and 5086 women) aged 75 yrs and over were recruited from general practice registers in Wessex, England. Primary outcome measure was all non-vertebral fracture. Secondary outcomes were hip and wrist fractures, and all falls.\n 585 subjects had incident non-spine fractures (hip 110, wrist 116, ankle 37). Hazard ratios (HRs) for fracture in the vitamin D group were: 1.09 [95% confidence interval (CI) 0.93-1.28, P = 0.29] for any first fracture, 1.49 (95% CI 1.02-2.18, P = 0.04) for hip and 1.22 (95% CI 0.85-1.76, P = 0.28) for wrist. There was no effect on falls: HR 0.98 (0.93-1.04). No protective effect was observed in any subgroup when the cohort was stratified by sex, age, previous fracture or mobility.\n An annual i.m. injection of 300,000 IU vitamin D2 is not effective in preventing non-vertebral fractures among elderly men and women resident in the general population.",
"The development of falls prevention strategies is an essential health concern in elderly people. However, a global consensus does not exist for elderly subjects who live independently in the community. The aim of the study was to evaluate the benefit of an exercises program.\n A control group (153 subjects) and an \"Intervention\" group (150 subjects) were tested before and after a 1-year prospective study. The \"Intervention\" group performed ten training sessions of physical activity, based on balance, muscular activity and coordination. We compared the incidence of falls, and the performances in several tests between the two groups.\n The clinical features were similar between the two groups: mean age 71 years, 83% of females, subjects who were independent for activities of daily living. However, all subjects presented risk for factors for falls: 38% were not able to maintain the unipodal position more than five seconds, 29% had already fallen during the previous year. For the \"Intervention\" group, the comparison of the performances before and after the physical activity program showed significant increases (p < 0.001) for all the tests, and specifically for the unipodal position and for the exercises performed with eyes closed. After one year follow-up, the incidence rate of falls was lower in the \"Intervention\" group compared with the control group, but the difference was not significant (p = 0.32). However, falls occurred significantly latter in the \"Intervention\" group (p = 0.02).\n Ten training sessions of physical activity allowed to improve the performance of elderly people in several tests. This result suggests that a fall prevention program based on collective and regular exercises, may be efficient for elderly subjects who still have an active and independent way of live.",
"To determine the effects of moderate intensity group-exercise programs on falls, functional performance, and disability in older adults; and to investigate the influence of frailty on these effects.\n A 20-week, multicenter randomized controlled trial, with 52-week follow-up.\n Fifteen homes for the elderly.\n Two hundred seventy-eight men and women (mean age +/- standard deviation, 85+/-6y).\n Two exercise programs were randomly distributed across 15 homes. The first program, functional walking (FW), consisted of exercises related to daily mobility activities. In the second program, in balance (IB), exercises were inspired by the principles of Tai Chi. Within each home participants were randomly assigned to an intervention or a control group. Participants in the control groups were asked not to change their usual pattern of activities. The intervention groups followed a 20-week exercise program with 1 meeting a week during the first 4 weeks and 2 meetings a week during the remaining weeks.\n Falls, Performance Oriented Mobility Assessment (POMA), physical performance score, and the Groningen Activity Restriction Scale (GARS) (measuring self-reported disability).\n Fall incidence rate was higher in the FW group (3.3 falls/y) compared with the IB (2.4 falls/y) and control (2.5 falls/y) groups, but this difference was not statistically significant. The risk of becoming a faller in the exercise groups increased significantly in the subgroup of participants who were classified as being frail (hazard ratio [HR] = 2.95; 95% confidence interval [CI], 1.64-5.32). For participants who were classified as being pre-frail, the risk of becoming a faller decreased; this effect became significant after 11 weeks of training (HR = .39; 95% CI, .18-.88). Participants in both exercise groups showed a small, but significant improvement in their POMA and physical performance scores. In the FW group, this held true for the GARS score as well. Post hoc analyses revealed that only the pre-frail participants improved their POMA and physical performance scores.\n Fall-preventive moderate intensity group-exercise programs have positive effects on falling and physical performance in pre-frail, but not in frail elderly.",
"Falls in elderly people are a common presenting complaint to accident and emergency departments. Current practice commonly focuses on the injury, with little systematic assessment of the underlying cause, functional consequences, and possibilities for future prevention. We undertook a randomised controlled study to assess the benefit of a structured inderdisciplinary assessment of people who have fallen in terms of further falls.\n Eligible patients were aged 65 years and older, lived in the community, and presented to an accident and emergency department with a fall. Patients assigned to the intervention group (n=184) underwent a detailed medical and occupational-therapy assessment with referral to relevant services if indicated; those assigned to the control group (n=213) received usual care only. The analyses were by intention to treat. Follow-up data were collected every 4 months for 1 year.\n At 12-month follow-up, 77% of both groups remained in the study. The total reported number of falls during this period was 183 in the intervention group compared with 510 in the control group (p=0.0002). The risk of falling was significantly reduced in the intervention group (odds ratio 0.39 [95% CI 0.23-0.66]) as was the risk of recurrent falls (0.33 [0.16-0.68]). In addition, the odds of admission to hospital were lower in the intervention group (0.61 [0.35-1.05]) whereas the decline in Barthel score with time was greater in the control group (p<0.00001).\n The study shows that an interdisciplinary approach to this high-risk population can significantly decrease the risk of further falls and limit functional impairment.",
"Sunlight exposure by improving vitamin D status could be a simple public health strategy in reducing falls among frail elder people. In a randomised controlled trial, adherence to sunlight exposure was low (median adherence, 26%) and no effect of increased UV exposure on falls risk was observed (incidence rate ratio (IRR) 1.06, P = 0.73).\n This study aimed to determine whether increased sunlight exposure was effective to improve vitamin D status and reduce falls in the elderly.\n In a cluster randomised controlled trial (NCT00322166 at ClinicalTrials.gov), 602 residents aged 70 or more (mean age, 86.4 years; 71% female) were recruited from 51 aged care facilities in Northern Sydney, Australia. Participants were randomised by facility to receive either increased sunlight exposure (additional 30-40 min/day in the early morning) with (UV+) or without (UV) calcium supplementation (600 mg/day) or neither (control) for a year. The co-primary endpoints were change in serum 25 hydroxy vitamin D (25OHD) and falls incidence after 12 months.\n Adherence to sunlight exposure was low (median adherence, 26%; IQR, 7%-45%). Serum 25OHD levels were low at baseline (median, 32.9 nmol/L) and increased only slightly depending on the number of sunlight sessions attended over 12 months (P = 0.04). During the study, 327 falls occurred in 111 (54%) subjects in the control group, 326 falls in 111 (58%) subjects in the UV only group and 335 falls in 108 (52%) subjects in the UV+ group. By intention-to-treat analysis, there was no significant effect of increased UV exposure on falls risk (IRR, 1.06; 95% CI, 0.76-1.48; P = 0.73). However, in 66 participants who attended ≥130 sessions per year (adherence, ≥50% of 260 sessions-five per week), falls were significantly reduced (IRR, 0.52; 95% CI, 0.31-0.88; P = 0.01) compared with the control group.\n Increased sunlight exposure did not reduce vitamin D deficiency or falls risk in frail older people. This public health strategy was not effective most likely due to poor adherence to the intervention.",
"To assess the effectiveness of a multivitamin (MV) tablet on nutritional status, quantitative heel ultrasound (QUS), mobility, muscle strength and falls. The design comprised two groups matched on mobility levels, randomized to receive a daily MV or placebo (P) tablet for 6 months. The setting was an Australian residential care facility.\n A total of 92 aged care residents. Serum micronutrients, body weight, QUS, rate of falls, hand grip strength, and the timed up and go test were assessed at baseline and 6 months.\n A total of 49 participants consumed a MV and 43, a matched P for 6 months. There was a greater increase in the MV vs P group for serum 25(OH)D (mean difference+/-standard error, 33.4+/-2.6 nmol l(-1)), folate (13.4+/-2.8 nmol l(-1)), and vitamin B12 (178.0+/-40.3 pmol l(-1)) (all P<0.001). Adequate 25(OH)D concentrations (> or =50 nmol l(-1)) were found among 77% of participants in the MV group vs 10% taking P (P<0.001). Adjusting for baseline levels, the increase in QUS was greater in the MV vs P group (3.0+/-2.0 dB MHz(-1) vs -2.9+/-2.1 dB MHz(-1), respectively, P=0.041). There was a trend towards a 63% lower mean number of falls in the MV vs P group (0.3+/-0.1 falls vs 0.8+/-0.3 falls, P=0.078).\n MV supplementation raised serum vitamin B12 and folate concentrations and increased serum 25(OH)D, which was accompanied by an apparent positive effect on bone density. We also found a trend towards a reduction in falls and this could contribute to a reduction in fractures.",
"To evaluate whether a programme of multifactorial home visits reduces falls and impairments in mobility in elderly people living in the community.\n Randomised controlled trial with 18 months of follow up.\n Six general practices in Hoensbroek, the Netherlands.\n 316 people aged 70 and over living in the community, with moderate impairments in mobility or a history of recent falls.\n Five home visits by a community nurse over a period of one year. Visits consisted of screening for medical, environmental, and behavioural factors causing falls and impairments in mobility, followed by specific advice, referrals, and other actions aimed at dealing with the observed hazards.\n Falls and impairments in mobility.\n No differences were found in falls and mobility outcomes between the intervention and usual care groups.\n Multifactorial home visits had no effects on falls and impairments in mobility in elderly people at risk who were living in the community. Because falls and impairments in mobility remain a serious problem among elderly people, alternative strategies should be developed and evaluated.",
"To assess whether supplementation with calcium and cholecaliferol (vitamin D3) reduces the risk of fracture in women with one or more risk factors for fracture of the hip.\n Pragmatic open randomised controlled trial.\n Practice nurse led clinics in primary care.\n 3314 women aged 70 and over with one or more risk factors for hip fracture: any previous fracture, low body weight (< 58 kg), smoker, family history of hip fracture, or fair or poor self reported health.\n Daily oral supplementation using 1000 mg calcium with 800 IU cholecaliferol and information leaflet on dietary calcium intake and prevention of falls, or leaflet only (control group).\n Primary outcome measure was all clinical fractures and secondary outcome measures were adherence to treatment, falls, and quality of life (measured with the SF-12).\n 69% of the women who completed the follow-up questionnaire at 24 months were still taking supplements (55% with inclusion of randomised participants known to be alive). After a median follow-up of 25 months (range 18 to 42 months), clinical fracture rates were lower than expected in both groups but did not significantly differ for all clinical fractures (odds ratio for fracture in supplemented group 1.01, 95% confidence interval 0.71 to 1.43). The odds ratio for hip fracture was 0.75 (0.31 to 1.78). The odds of a woman having a fall at six and 12 months was 0.99 and 0.98, respectively. Quality of life did not significantly differ between the groups.\n We found no evidence that calcium and vitamin D supplementation reduces the risk of clinical fractures in women with one or more risk factors for hip fracture. Registration ISRCTN26118436, controlled trials registry.",
"A recent meta-analysis found that cholecalciferol (vitamin D) should reduce falls by more than 20%. However, little is known about whether supplemental cholecalciferol plus calcium citrate malate will lower the long-term risk of falling in men, active older individuals, and older individuals with higher 25-hydroxyvitamin D levels.\n We studied the effect of 3-year supplementation with cholecalciferol-calcium on the risk of falling at least once in 199 men and 246 women 65 years or older and living at home. Individuals received 700 IU of cholecalciferol plus 500 mg of calcium citrate malate per day or placebo in a randomized double-blind manner. Subjects were classified as less physically active if physical activity was below the median level. Low 25-hydroxyvitamin D levels were classified as those below 32 ng/mL (<80 nmol/L).\n In 3 years, 55% of women and 45% of men reported at least 1 fall. Mean +/- SD baseline 25-hydroxyvitamin D levels were 26.6 +/- 12.7 ng/mL (66.4 +/- 31.7 nmol/L) in women and 33.2 +/- 14.2 ng/mL (82.9 +/- 34.9) in men. Cholecalciferol-calcium significantly reduced the odds of falling in women (odds ratio [OR], 0.54; 95% confidence interval [CI], 0.30-0.97), but not in men (OR, 0.93; 95% CI, 0.50-1.72). Fall reduction was most pronounced in less active women (OR, 0.35; 95% CI, 0.15-0.81). Baseline 25-hydroxyvitamin D level did not modulate the treatment effect.\n Long-term dietary cholecalciferol-calcium supplementation reduces the odds of falling in ambulatory older women by 46%, and especially in less active women by 65%. Supplementation had a neutral effect in men independent of their physical activity level.",
"Elevated circulating concentrations of proinflammatory cytokines may contribute to the pathogenesis of congestive heart failure (CHF). In vitro studies suggest that vitamin D suppresses proinflammatory cytokines and increases antiinflammatory cytokines.\n We evaluated the effect of vitamin D supplementation on the survival rate and different biochemical variables in patients with CHF.\n One hundred twenty-three patients randomly received either 50 mug vitamin D(3)/d plus 500 mg Ca/d [D(+) group] or placebo plus 500 mg Ca/d [D(-) group] for 9 mo. Biochemical variables were assessed at baseline and after 9 mo. The survival rate was calculated for a follow-up period of 15 mo.\n Ninety-three patients completed the study. Significant treatment effects were observed on logarithmic-transformed serum concentrations of 25-hydroxyvitamin D (P = 0.001), parathyroid hormone (P = 0.007), tumor necrosis factor alpha (P = 0.006), and interleukin 10 (P = 0.042). 25-Hydroxyvitamin D increased by 26.8 ng/mL in the D(+) group but increased only by 3.6 ng/mL in the D(-) group. Compared with baseline, parathyroid hormone was significantly lower and the antiinflammatory cytokine interleukin 10 was significantly higher in the D(+) group after 9 mo. The proinflammatory cytokine tumor necrosis factor alpha increased in the D(-) group but remained constant in the D(+) group. The survival rate did not differ significantly between the study groups during the follow-up period.\n Vitamin D(3) reduces the inflammatory milieu in CHF patients and might serve as a new antiinflammatory agent for the future treatment of the disease. Our data provide evidence for the involvement of an impaired vitamin D-parathyroid hormone axis in the progression of CHF.",
"To assess the effectiveness of a targeted, multiple intervention falls prevention programme in reducing falls and injuries related to falls in a subacute hospital.\n Randomised controlled trial of a targeted multiple intervention programme implemented in addition to usual care compared with usual care alone.\n Three subacute wards in a metropolitan hospital specialising in rehabilitation and care of elderly patients.\n 626 men and women aged 38 to 99 years (average 80 years) were recruited from consecutive admissions to subacute hospital wards.\n Falls risk alert card with information brochure, exercise programme, education programme, and hip protectors.\n Incidence rate of falls, injuries related to falls, and proportion of participants who experienced one or more falls during their stay in hospital.\n Participants in the intervention group (n = 310) experienced 30% fewer falls than participants in the control group (n = 316). This difference was significant (Peto log rank test P = 0.045) and was most obvious after 45 days of observation. In the intervention group there was a trend for a reduction in the proportion of participants who experienced falls (relative risk 0.78, 95% confidence interval 0.56 to 1.06) and 28% fewer falls resulted in injury (log rank test P = 0.20).\n A targeted multiple intervention falls prevention programme reduces the incidence of falls in the subacute hospital setting.",
"to assess whether specialist osteoporosis nurses delivering training to care home staff can reduce fractures and improve the prescription of treatments to reduce fractures versus usual care.\n pragmatic cluster randomised controlled trial (RCT) with randomisation at the Primary Care Organisation (PCO) level.\n care homes (residential, nursing and EMI) across England and Wales within PCOs.\n all 300 PCOs in England and Wales were invited to take part. Of these, 58 agreed to participate and gained ethical approval in time to start the study: 29 clusters were randomised to the intervention group and 29 to the control.\n specialist osteoporosis nurses undertaking short training sessions with care home staff emphase the importance of fracture and fall prevention and train staff on how to identify those residents at high risk of fracture. Residents' risk of fracture and falls was reported to general practitioners (GPs) of patients along with treatment recommendations.\n primary outcome measures were total fractures over the past 12 months and total hip fractures over past the 12 months. Secondary outcome measures were total home falls, number of residents sustaining a fall, number of residents prescribed bisphosphonates, number of residents prescribed calcium and vitamin D and number of residents wearing hip protectors. All outcomes were measured at the care home level.\n of the 230 care homes randomised data were collected from 209 of these containing 5,637 residents. There were no differences between the groups in the incidence rate ratios (IRRs) for total fractures (IRR = 0.94 [0.71, 1.26] P = 0.70) or total hip fractures (IRR = 0.86 [0.63, 1.18] P = 0.36). No differences were found between groups for home falls or hip protector use. A significant increase in bisphosphonate prescription was seen in the intervention group over the control group (IRR = 1.50 [1.00, 2.24] P = 0.05). Calcium and vitamin D prescription was significantly increased in the intervention group over the control group (IRR = 1.64 [1.23, 2.18] P<0.01).\n the intervention significantly increased the prescription of bisphosphonates and calcium/vitamin D, but was not associated with a significant effect on the rate of falls or fractures.",
"To assess the effectiveness of a community-based falls-and-fracture nurse coordinator and multifactorial intervention in reducing falls in older people.\n Randomized, controlled trial.\n Screening for previous falls in family practice followed by community-based intervention.\n Three hundred twelve community-living people aged 75 and older who had fallen in the previous year.\n Home-based nurse assessment of falls-and-fracture risk factors and home hazards, referral to appropriate community interventions, and strength and balance exercise program. Control group received usual care and social visits.\n Primary outcome was rate of falls over 12 months. Secondary outcomes were muscle strength and balance, falls efficacy, activities of daily living, self-reported physical activity level, and quality of life (Medical Outcomes Study 36-item Short Form Questionnaire).\n Of the 3,434 older adults screened for falls, 312 (9%) from 19 family practices were enrolled and randomized. The average age was 81+/-5, and 69% (215/312) were women. The incidence rate ratio for falls for the intervention group compared with the control group was 0.96 (95% confidence interval=0.70-1.34). There were no significant differences in secondary outcomes between the two groups.\n This nurse-led intervention was not effective in reducing falls in older people who had fallen previously. Implementation and adherence to the fall-prevention measures was dependent on referral to other health professionals working in their usual clinical practice. This may have limited the effectiveness of the interventions.",
"The present study was conducted to determine the effect of 5-month exercise program on the prevention of falls in the elderly. The exercise training, which consisted of calisthenics, body balance training, muscle power training, and walking ability training 3 days/week improved the indices of the flexibility, body balance, muscle power, and walking ability and reduced the incidence of falls compared with non-exercise controls. The present study showed the beneficial effect of the exercise program aimed at improving flexibility, body balance, muscle power, and walking ability in preventing falls in the elderly.\n The present study was conducted to determine the effect of exercise on the prevention of falls in the elderly.\n Sixty-eight elderly ambulatory volunteers were randomly divided into two groups: the exercise and control groups. The daily exercise, which consisted of calisthenics, body balance training (tandem standing, tandem gait, and unipedal standing), muscle power training (chair-rising training), and walking ability training (stepping), were performed 3 days/week only in the exercise group. No exercise was performed in the control group.\n After the 5-month exercise program, the indices of the flexibility, body balance, muscle power, and walking ability significantly improved in the exercise group compared with the control group. The incidence of falls was significantly lower in the exercise group than in the control group (0.0% vs. 12.1%, P = 0.0363). The exercise program was safe and well tolerated in the elderly.\n The present study showed the beneficial effect of the exercise program aimed at improving flexibility, body balance, muscle power, and walking ability in preventing falls in the elderly.",
"Exercise interventions can enhance mobility after stroke as well as prevent falls in elderly persons.\n Investigate whether an exercise intervention can enhance mobility, prevent falls, and increase physical activity among community-dwelling people after stroke.\n A randomized trial with blinding of physical outcome assessment was conducted through local stroke clubs. Both groups, on average 5.9 years poststroke, received exercise classes, advice, and a home program for 12 months. The experimental group (EG) program (n = 76) aimed to improve walking, prevent falls and increase physical activity. The control group (CG) program (n = 75) aimed to improve upper-limb and cognitive functions. The primary outcomes were walking capacity, walking speed measured before and after the intervention, and fall rates monitored monthly.\n At 12 months, the EG walked 34 m further in 6 minutes (95% confidence interval [CI] = 19-50; P < .001) and 0.07 m/s faster over 10 m (95% CI = 0.01-0.14; P = .03) than the CG. The EG had 129 falls, and the CG had 133. There were no differences in proportion of fallers (relative risk = 1.22; 95% CI = 0.91-1.62; P = .19) or the rate of falls between groups (incidence rate ratio = 0.96; 95% CI = 0.59-1.51; P = .88).\n The experimental intervention delivered through stroke clubs enhanced aspects of mobility but had no effect on falls.",
"Multifaceted programs that combine assessment with interventions have been shown to reduce subsequent falls in some clinical trials. We tested this approach to see whether it would be effective if offered as a consultation service using existing health care resources.\n The subjects of this randomized controlled trial had to be aged 65 years or more and had to have fallen within the previous 3 months. They were randomly assigned to receive either usual care or the intervention, which consisted of in-home assessment in conjunction with the development of an individualized treatment plan, including an exercise program for those deemed likely to benefit. The primary outcomes were the proportion of participants who fell and the rate of falling during the following year. Visits to the emergency department and admissions to hospital were secondary outcomes.\n One hundred and sixty-three subjects were randomly assigned to either the control or the intervention group, and 152 provided data about their falls. There were no significant differences between the control and intervention groups in the cumulative number of falls (311 v. 241, p = 0.34), having one or more falls (79.2% v. 72.0%, p = 0.30) or in the mean number of falls (4.0 v. 3.2, p = 0.43). Analysis of secondary outcomes (health care use) also showed no significant differences between the intervention group and the control group. In the Cox regression analysis, there was no significant difference between the groups in the proportion of subjects having one or more falls (p = 0.55), but there was a significantly (p < 0.001) longer time between falls in the intervention group. In a post hoc subgroup analysis, subjects with more than 2 falls in the 3 months preceding study entry who had been assigned to the intervention group were less likely to fall (p = 0.046) and had a significantly longer time between falls (p < 0.001), when compared with the group who received usual care.\n The intervention did not decrease significantly the cumulative number of falls, the likelihood of participants having at least one fall over the next year or the mean number of falls. It did increase significantly the time between falls in a survival analysis when age, sex and history of falling were used as covariates.",
"This study determined the effects and costs of a multifactorial, interdisciplinary team approach to falls prevention. Randomized controlled trial of 109 older adults who are at risk for falls. This was a six-month multifactorial and evidence-based prevention strategy involving an interdisciplinary team. The primary outcome was number of falls during the six-month follow-up. At six months, no difference in the mean number of falls between groups. Subgroup analyses showed that the intervention effectively reduced falls in men (75-84 years old) with a fear of falling or negative fall history. Number of slips and trips was greatly reduced; and emotional health had a greater improvement in role functioning related to emotional health in the intervention group. Quality of life was improved, slips and trips were reduced, as were falls among males (75-84 years old) with a fear of falling or negative fall history.",
"To determine the effectiveness of multifactorial intervention to prevent falls in cognitively intact older persons with recurrent falls.\n Randomised controlled trial of multifactorial (medical, physiotherapy and occupational therapy) post-fall assessment and intervention compared with conventional care.\n Accident & Emergency departments in a university teaching hospital and associated district general hospital.\n 313 cognitively intact men and women aged over 65 years presenting to Accident & Emergency with a fall or fall-related injury and at least one additional fall in the preceding year; 159 randomised to assessment and intervention and 154 to conventional care. Outcome measures: primary outcome was the number of falls and fallers in 1 year after recruitment. Secondary outcomes included injury rates, fall-related hospital admissions, mortality and fear of falling.\n There were 36% fewer falls in the intervention group (relative risk 0.64, 95% confidence interval 0.46-0.90). The proportion of subjects continuing to fall (65% (94/144) compared with 68% (102/149) relative risk 0.95, 95% confidence interval 0.81-1.12), and the number of fall-related attendances and hospital admissions was not different between groups. Duration of hospital admission was reduced (mean difference admission duration 3.6 days, 95% confidence interval 0.1-7.6) and falls efficacy was better in the intervention group (mean difference in Activities Specific Balance Confidence Score of 7.5, 95% confidence interval 0.72-14.2).\n Multifactorial intervention is effective at reducing the fall burden in cognitively intact older persons with recurrent falls attending Accident & Emergency, but does not reduce the proportion of subjects still falling.",
"To evaluate the efficacy of the Nijmegen Falls Prevention Program (NFPP) for persons with osteoporosis and a fall history in a randomized controlled trial. Persons with osteoporosis are at risk for fall-related fractures because of decreased bone strength. A decrease in the number of falls therefore is expected to be particularly beneficial for these persons.\n Randomized controlled trial.\n Hospital.\n Persons with osteoporosis and a fall history (N=96; mean ± SD age, 71.0±4.7y; 90 women).\n After baseline assessment, participants were randomly assigned to the exercise (n=50; participated in the NFPP for persons with osteoporosis [5.5wk]) or control group (n=46; usual care).\n Primary outcome measure was fall rate, measured by using monthly fall calendars for 1 year. Secondary outcomes were balance confidence (Activity-specific Balance Confidence Scale), quality of life (QOL; Quality of Life Questionnaire of the European Foundation for Osteoporosis), and activity level (LASA Physical Activity Questionnaire, pedometer), assessed posttreatment subsequent to the program and after 1 year of follow-up.\n The fall rate in the exercise group was 39% lower than for the control group (.72 vs 1.18 falls/person-year; risk ratio, .61; 95% confidence interval, .40-.94). Balance confidence in the exercise group increased by 13.9% (P=.001). No group differences were observed in QOL and activity levels.\n The NFPP for persons with osteoporosis was effective in decreasing the number of falls and improving balance confidence. Therefore, it is a valuable new tool to improve mobility and independence of persons with osteoporosis.\n Copyright © 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.",
"To compare the efficacy of seated exercises and weight-bearing (WB) exercises with social visits on fall risk factors in older people recently discharged from hospital.\n Twelve-week randomized, controlled trial.\n Home-based exercises.\n Subjects (N=180) aged 65 and older, recently discharged from hospital.\n Seated exercises (n=60), WB exercises (n=60), and social visits (n=60).\n Primary outcome factors were Physiological Profile Assessment (PPA) fall risk score, and balance while standing (Coordinated Stability and Maximal Balance Range tests). Secondary outcomes included the component parts of the PPA and other physical and psychosocial measures.\n Subjects were tested at baseline and at completion of the intervention period. After 12 weeks of interventions, subjects in the WB exercise group had significantly better performance than the social visit group on the following: PPA score (P=.048), Coordinated Stability (P<.001), Maximal Balance Range (P=.019); body sway on floor with eyes closed (P=.017); and finger-press reaction time (P=.007) tests. The seated exercise group performed better than the social visit group in PPA score (P=.019) but for no other outcome factor. The seated exercise group had the highest rate of musculoskeletal soreness.\n In older people recently discharged from the hospital, both exercise programs reduced fall risk score in older people. The WB exercises led to additional beneficial impacts for controlled leaning, reaction time, and caused less musculoskeletal soreness than the seated exercises.",
"Falls in the elderly are a major health problem. Although exercise programs have been shown to reduce the risk of falls, the optimal exercise components, as well as the working mechanisms that underlie the effectiveness of these programs, have not yet been established.\n To test whether the Nijmegen Falls Prevention Program was effective in reducing falls and improving standing balance, balance confidence, and obstacle avoidance performance in community-dwelling elderly people.\n A total of 113 elderly with a history of falls participated in this study (exercise group, n = 79; control group, n = 28; dropouts before randomization, n = 6). Exercise sessions were held twice weekly for 5 weeks. Pre- and post-intervention fall monitoring and quantitative motor control assessments were performed. The outcome measures were the number of falls, standing balance and obstacle avoidance performance, and balance confidence scores.\n The number of falls in the exercise group decreased by 46% (incidence rate ratio (IRR) 0.54, 95% confidence interval (CI) 0.36-0.79) compared to the number of falls during the baseline period and by 46% (IRR 0.54, 95% CI 0.34-0.86) compared to the control group. Obstacle avoidance success rates improved significantly more in the exercise group (on average 12%) compared to the control group (on average 6%). Quiet stance and weight-shifting measures did not show significant effects of exercise. The exercise group also had a 6% increase of balance confidence scores.\n The Nijmegen Falls Prevention Program was effective in reducing the incidence of falls in otherwise healthy elderly. There was no evidence of improved control of posture as a mechanism underlying this result. In contrast, an obstacle avoidance task indicated that subjects improved their performance. Laboratory obstacle avoidance tests may therefore be better instruments to evaluate future fall prevention studies than posturographic balance assessments.\n Copyright (c) 2006 S. Karger AG, Basel.",
"Care of elderly patients after hip fracture is not well established.\n We enrolled 173 patients with acute hip fracture who were 65 years or older (79.2% women; mean age, 84 years; 77.4% living at home). Using a factorial design, we randomly allocated patients to extended physiotherapy (PT) (supervised 60 min/d during acute care plus an unsupervised home program) vs standard PT (supervised 30 min/d during acute care plus no home program; single-blinded), and to cholecalciferol therapy, 2000 vs 800 IU/d (double-blinded). Primary outcome was rate of falls; secondary outcome was rate of hospital readmissions during the 12-month follow-up. All analyses included 173 individuals and used multivariate Poisson regression analyses.\n At baseline, 50.9% of participants had 25-hydroxyvitamin D levels of less than 12 ng/mL and 97.7% of less than 30 ng/mL. We documented 212 falls and 74 hospital readmissions. Because this was a factorial design trial, all analyses tested the main effect of each treatment while controlling for the other in 173 participants. Extended vs standard PT reduced the rate of falls by 25% (95% confidence interval [CI], -44% to -1%). Cholecalciferol treatment, 2000 vs 800 IU/d, did not reduce falls (28%; 95% CI, -4% to 68%), but reduced the rate of hospital readmissions by 39% (95% CI, -62% to -1%).\n Extended PT was successful in reducing falls but not hospital readmissions, whereas cholecalciferol treatment, 2000 IU/d, was successful in reducing hospital readmission but not falls. Thus, the 2 strategies may be useful together because they address 2 different and important complications after hip fracture.",
"falls and related injuries are known to be a significant problem for older people. There is evidence that identifying and addressing individual risk factors can reduce the incidence of falls in the community but no evidence of the effectiveness of targeted risk factor reduction methods applied to hospital in-patients.\n to test the efficacy of a targeted risk factor reduction core care plan in reducing risk of falling while in hospital.\n a group (ward) randomised trial.\n elderly care wards and associated community units of a district general hospital in the North of England.\n all elderly patients who received care in eight wards and community units during a 12-month study period.\n matched pairs of wards were randomly allocated to intervention or control groups. In the intervention wards, staff used a pre-printed care plan for patients identified as at risk of falling and introduced appropriate remedial measures. Numbers of falls in each group were then compared.\n after introduction of the care plan there was a significant reduction in the relative risk of recorded falls on intervention wards (relative risk 0.79, 95% CI 0.65-0.95) but not on control wards (RR 1.12, 95% CI 0.96-1.31). The difference in change between the intervention wards and control wards was highly significant (RR 0.71, 95% CI 0.55-0.90, P = 0.006). There was no significant reduction in the incidence of falls-related injuries.\n the use of a core care plan targeting risk factor reduction in older hospital in-patients was associated with a reduction in the relative risk of recorded falls.",
"Current health education programs for osteoporosis prevention are not strictly evidence-based. We assessed whether distribution of an evidence-based guideline improved such programs at municipal health centers.\n This randomized controlled trial evaluated 100 municipal health centers throughout Japan that were randomly selected from those that planned to revise osteoporosis prevention programs. The implementation status of educational items recommended by the guideline was assessed before and after the intervention by evaluators blinded to the allocation. After the pre-intervention assessment, centers were randomly allocated in a 1:1 ratio to intervention and control groups by a minimization method defining region and city/town as stratification factors. Centers in the intervention group were given copies of the guideline; centers in the control group were instructed to use any information except the guideline. Analyses were performed on an intention-to-treat basis.\n The guideline was used by 50% of the intervention group. Before the intervention, there was no significant difference in the evidence-based status of health education between the groups. The post-intervention assessment showed that the implementation rates of health education on dietary calcium intake for postmenopausal women and exercise for elderly persons were higher in the intervention group. Specific advice on intakes of calcium and vitamin D and exercise became more evidence-based in the intervention group.\n The findings suggest that the guideline helped healthcare professionals to improve health education programs by making them more evidence-based. However, the improvements seemed to be limited to items that the professionals felt prepared to improve.",
"A randomized double-blind controlled trial of the effect of vitamin D supplementation on the abilities of elderly hospital patients to carry out basic activities of daily life is described. Those patients included in the trial had plasma 25-hydroxyvitamin D concentrations which were low or low normal as judged by the normal range in young adults. After 2 to 9 months on the trial there was no significant difference in the performance of the control and treatment groups.",
"To determine the relative effect of education and activity programs on fear of falling, balance, strength, and health status.\n A randomized intervention trial with two groups (education and activity); evaluators were blind to group allocation.\n Motor performance laboratory at Queen's University.\n Thirty-eight community-dwelling seniors who reported a fear of falling and activity restriction but were free of neurological and mobility-limiting orthopedic conditions.\n Programs designed to reduce fear of falling were delivered weekly to groups of three to five seniors for 8 weeks, each session lasting 1 hour. The activity program included low-resistance exercises and weight-shifting activities. Education focused on identifying and reducing risk factors for falls.\n Balance confidence, activity level, limits of stability (LOS), isokinetic strength, and health status were measured twice preintervention (baseline), postintervention, and 6 weeks later.\n Both programs reduced fear of falling (P <.006) as ascertained from the balance confidence scores. Differential effects were observed in LOS (P <.05); activity improved balance, whereas education led to modest declines. Gains in perception of health status were limited to physical health for the activity group and mental health for the education group. Benefits were generally sustained at follow-up.\n Improved balance confidence is not intervention-specific, but associated changes in physical ability and health status are a function of the composition of the intervention program.",
"To compare the effects of three fall-prevention programs (education (ED), home safety assessment and modification (HSAM), and exercise training (ET)) on quality of life (QOL), functional balance and gait, activities of daily living (ADLs), fear of falling, and depression in adults aged 65 and older.\n A 4-month randomized trial.\n Randomized, controlled trial.\n One hundred fifty participants who had experienced a recent fall.\n QOL was assessed according to the brief version of the World Health Organization Quality of Life instrument (WHOQOL-BREF), functional balance and gait according to functional reach and Tinetti balance and gait, ADLs according to the Older Americans Resources and Services questionnaire, fear of falling according to a visual analog scale, and depression level according to the Geriatric Depression Scale.\n The score changes for the ET group were 2.1 points greater on the physical domain (95% confidence interval (CI)=-1.2-5.3), 3.8 points greater on the psychological domain (95% CI=0.7-7.0), and for the WHOQOL-BREF, 3.4 points greater on the social domain (95% CI=0.7-6.1) and 3.2 points greater on the environmental domain (95% CI=0.6-5.7) than for the ED group. The score change for each domain of the WHOQOL-BREF for the HSAM group was greater than that for the ED group, although these results were not statistically significant. The ET group also had greater improvements in functional reach, Tinetti balance and gait, and fear of falling than the ED group.\n The QOL outcome supports the superiority of ET over the other two interventions in older people who have recently fallen. This finding also parallels those gathered from the functional measures.",
"Although vitamin D supplementation has been suggested to reduce the risk of falling in ambulatory or institutionalized elderly persons, no study has examined whether it reduces the frequency of falling in immobilized stroke patients who have immobilization-induced hypercalcemia reflecting increased bone resorption leading to inhibited renal synthesis of 1, 25-dihydroxyvitamin D (1, 25-[OH]2D). Bisphosphonate is known to reduce immobilization-induced hypercalcemia by inhibiting bone resorption of calcium. This study compared the efficacy of 2 drugs in reducing the risk of falling in patients with long-standing stroke. Eighty-two elderly patients with poststroke hemiparesis were followed for 1 year. The patients were randomly assigned to one of 2 groups; 41 patients received alendronate 35 mg once weekly, and 41 patients received alphacalcidiol 1 μg daily. The number of falls per person and incidence of hip fracture in the 2 groups were compared. At baseline, all patients had a low serum 1, 25-[OH]2D level. Alphacalcidol therapy enhanced immobilization-induced hypercalcemia by increasing intestinal calcium absorption, leading to a reduction of serum 1, 25-[OH]2D level, while alendronate therapy enhanced 1, 25-[OH]2D production by decreasing hypercalcemia. Alendronate treatment accounted for a 55% reduction in falls (95% confidence interval [CI]=25-72%; P=.0021). During the 1-year study period, hip fracture occurred in 1 of 41 subjects in the alphacalcidol group and in no subjects in the alendronate group. Bone mineral density was increased by 3.2% in the alendronate group and decreased by 0.1% in the alphacalcidol group (P<.0001). Alendronate therapy increased serum 1, 25-[OH]2D levels by improving immobilization-induced hypercalcemia, which may lead to decreased falling and subsequent hip fractures.\n Copyright © 2011 National Stroke Association. Published by Elsevier Inc. All rights reserved.",
"Falls and resulting injuries are particularly common in older people living in residential care facilities, but knowledge about the prevention of falls is limited.\n To investigate whether a multifactorial intervention program would reduce falls and fall-related injuries.\n A cluster randomized, controlled, nonblinded trial.\n 9 residential care facilities located in a northern Swedish city.\n 439 residents 65 years of age or older.\n An 11-week multidisciplinary program that included both general and resident-specific, tailored strategies. The strategies comprised educating staff, modifying the environment, implementing exercise programs, supplying and repairing aids, reviewing drug regimens, providing free hip protectors, having post-fall problem-solving conferences, and guiding staff.\n The primary outcomes were the number of residents sustaining a fall, the number of falls, and the time to occurrence of the first fall. A secondary outcome was the number of injuries resulting from falls.\n During the 34-week follow-up period, 82 residents (44%) in the intervention program sustained a fall compared with 109 residents (56%) in the control group (risk ratio, 0.78 [95% CI, 0.64 to 0.96]). The adjusted odds ratio was 0.49 (CI, 0.37 to 0.65), and the adjusted incidence rate ratio of falls was 0.60 (CI, 0.50 to 0.73). Each of 3 residents in the intervention group and 12 in the control group had 1 femoral fracture (adjusted odds ratio, 0.23 [CI, 0.06 to 0.94]). Clustering was considered in all regression models.\n An interdisciplinary and multifactorial prevention program targeting residents, staff, and the environment may reduce falls and femoral fractures.",
"the burden of falls and fall-related injuries among older adults is well established. Contention surrounds the effectiveness, and hence value, of multi-component fall prevention interventions delivered in the community.\n using consensus-based analytic guidelines rather than time-to-first fall as the primary endpoint, the objective was to examine the effectiveness of the Whitehorse NoFalls trial on all falls, falls resulting in injury and falls requiring medical care to be sought. Design, setting and participants: the study was a community-based randomised controlled trial, with 1,090 participants assigned to one of eight groups, these being a combination of one or more of exercise, vision and or home hazard reduction or alternatively assignment to the control group.\n using negative binomial regression, the incidence of all falls, falls resulting in injury and those requiring medical care in the intervention groups were examined. Falls were reported using a monthly return calendar.\n exercise alone and in combination with vision and/or home hazard reduction was associated with fewer falls. For falls resulting in injury and the subset requiring medical care, the vision plus exercise intervention was associated with fewer falls.\n the findings confirm the effectiveness of exercise in preventing falls among community-dwelling older adults and supports contention that multi-component interventions do not prevent more falls than a single intervention. The results highlight the effectiveness of vision plus exercise in preventing more serious falls, a finding which warrants further consideration."
] |
Group and home-based exercise programmes, and home safety interventions reduce rate of falls and risk of falling.
Multifactorial assessment and intervention programmes reduce rate of falls but not risk of falling; Tai Chi reduces risk of falling.
Overall, vitamin D supplementation does not appear to reduce falls but may be effective in people who have lower vitamin D levels before treatment.
|
CD003738
|
[
"15313288",
"15342049",
"16005976",
"15808167",
"12106717",
"15629822",
"15050264",
"15121364",
"15715551",
"15975461",
"16168485",
"19185241",
"15506598",
"16931265",
"12954304",
"15453848",
"17124239",
"17399674",
"17553447",
"15465544",
"12954305",
"15899448",
"15983779",
"18321585",
"17318205",
"15130632",
"15093639",
"12113567",
"17010858",
"14736768",
"17822973",
"16581420",
"12648639",
"17321391",
"11190013",
"12948312",
"18655983",
"15030818",
"10646147",
"10831902",
"1501083",
"12646745",
"9159691",
"9474601",
"12353900",
"12449218",
"15519082",
"9869784",
"17202203",
"15148204",
"2668133",
"15299988",
"11008045",
"18721708",
"15148202",
"12446370",
"11566517",
"9917780",
"9437309",
"10463407",
"15617914"
] |
[
"Effect of a silicone intraocular lens with a sharp posterior optic edge on posterior capsule opacification.",
"Effect of intraocular lens optic edge design and material on fibrotic capsule opacification and capsulorhexis contraction.",
"Posterior capsule opacification in the presence of an intraocular lens with a sharp versus rounded optic edge.",
"Long-term efficacy of adding a sharp posterior optic edge to a three-piece silicone intraocular lens on capsule opacification: five-year results of a randomized study.",
"Effect of an acrylic intraocular lens with a sharp posterior optic edge on posterior capsule opacification.",
"Effect of optic material on posterior capsule opacification in intraocular lenses with sharp-edge optics: randomized clinical trial.",
"Influence of optic edge design and anterior capsule polishing on posterior capsule fibrosis.",
"Anterior capsule relationship of the AcrySof intraocular lens optic and posterior capsule opacification: a prospective randomized clinical trial.",
"Three-year follow-up of posterior capsule opacification with two different silicone intraocular lenses.",
"Long-term effect of optic edge design in an acrylic intraocular lens on posterior capsule opacification.",
"Long-term effect of sharp optic edges of a polymethyl methacrylate intraocular lens on posterior capsule opacification: a randomized trial.",
"Randomized intraindividual comparison of posterior capsule opacification between a microincision intraocular lens and a conventional intraocular lens.",
"The effects of three-piece or single-piece acrylic intraocular lens implantation on posterior capsule opacification.",
"Effect of anterior capsule polishing on the posterior capsule opacification-inhibiting properties of a sharp-edged, 3-piece, silicone intraocular lens: three- and 5-year results of a randomized trial.",
"Posterior capsule opacification after phacoemulsification: silicone CeeOn Edge versus acrylate AcrySof intraocular lens.",
"Position of anterior capsulorhexis and posterior capsule opacification.",
"Influence of three-piece and single-piece designs of two sharp-edge optic hydrophobic acrylic intraocular lenses on the prevention of posterior capsule opacification: a prospective, randomised, long-term clinical trial.",
"Long-term effect of optic edge design in a silicone intraocular lens on posterior capsule opacification.",
"Influence on posterior capsule opacification and visual function of intraocular lens optic material.",
"Comparison of posterior capsule opacification between the 1-piece and 3-piece Acrysof intraocular lenses: two-year results of a randomized trial.",
"Posterior capsule opacification: comparison of 3 intraocular lenses of different materials and design.",
"Comparison of posterior capsule opacification rates between hydrophilic and hydrophobic single-piece acrylic intraocular lenses.",
"[Quantitative evaluation of acrylic and silicone intraocular lenses with a sharp optic edge design].",
"Optic edge design as long-term factor for posterior capsular opacification rates.",
"Posterior capsule opacification after extra capsular cataract extraction in Indian rural population: foldable acrylic vs poly (methyl-methacrylate) intraocular lenses a randomized clinical trial.",
"Posterior capsule opacification after implantation of CeeOn Edge 911A, PhacoFlex SI-40NB, and AcrySof MA60BM lenses: one-year results of an intraindividual comparison multicenter study.",
"Effect of 1-piece and 3-piece AcrySof intraocular lenses on the development of posterior capsule opacification after cataract surgery.",
"Posterior capsular opacification in pseudophakic eyes with a silicone or acrylic intraocular lens.",
"Posterior capsule opacification after implantation of a hydrophilic or a hydrophobic acrylic intraocular lens: one-year follow-up.",
"Posterior capsule opacification after implantation of a hydrogel intraocular lens.",
"Long-term effect of 1-piece and 3-piece hydrophobic acrylic intraocular lens on posterior capsule opacification: a randomized trial.",
"Prospective intrapatient comparison of 6.0-millimeter optic single-piece and 3-piece hydrophobic acrylic foldable intraocular lenses.",
"Morphological and functional results of AcrySof intraocular lens implantation in children: prospective randomized study of age-related surgical management.",
"Fellow-eye comparison of posterior capsule opacification rates after implantation of 1CU accommodating and AcrySof MA30 monofocal intraocular lenses.",
"Incidence of postoperative posterior capsular opacification following treatment with diclofenac 0.1% and ketorolac 0.5% ophthalmic solutions: 3-year randomized, double-masked, prospective clinical investigation.",
"The effect of capsulorhexis size on development of posterior capsule opacification: small (4.5 to 5.0 mm) versus large (6.0 to 7.0 mm).",
"Efficacy and safety of capsular bending ring implantation to prevent posterior capsule opacification: three-year results of a randomized clinical trial.",
"Posterior capsule opacification after phacoemulsification in patients with postoperative steroidal and nonsteroidal treatment.",
"Digital retroilluminated photography to analyze posterior capsule opacification in eyes with intraocular lenses.",
"Double-masked prospective ocular safety study of a lens epithelial cell antibody to prevent posterior capsule opacification.",
"Effect of posterior chamber intraocular lens design and surgical placement on postoperative outcome.",
"Three-year prospective randomized study of incidence of posterior capsule opacification in eyes treated with topical diclofenac and betamethasone.",
"Heparin eyedrops to prevent posterior capsule opacification.",
"Silicone versus polymethylmethacrylate intraocular lenses with regard to capsular opacification.",
"Posterior continuous curvilinear capsulorhexis with and without optic capture of the posterior chamber intraocular lens in the absence of vitrectomy.",
"Clinical evaluation of posterior capsule opacification in eyes with different small-incision intraocular lenses.",
"Effect of anterior capsule polishing on fibrotic capsule opacification: three-year results.",
"Quantitative comparison of posterior capsule opacification after polymethylmethacrylate, silicone, and soft acrylic intraocular lens implantation.",
"Long-term results of sealed capsule irrigation using distilled water to prevent posterior capsule opacification: a prospective clinical randomised trial.",
"A prospective, randomised comparison of single and three piece acrylic foldable intraocular lenses.",
"[Postoperative cataract following intraocular lenses with and without laser ridge].",
"Prevention of posterior capsule opacification using different intraocular lenses (results of one-year clinical study).",
"Posterior capsule opacification 3 years after implantation of an AcrySof and a MemoryLens in fellow eyes.",
"Fellow-eye comparison of posterior capsule opacification with AcrySof SN60AT and AF-1 YA-60BB blue-blocking intraocular lenses.",
"A comparison of anterior and posterior chamber lenses after cataract extraction in rural Africa: a within patient randomised trial.",
"Effects of dexamethasone, diclofenac, or placebo on the inflammatory response after cataract surgery.",
"Effect of intraocular lens haptic compressibility on the posterior lens capsule after cataract surgery.",
"The effect of polymethylmethacrylate, silicone, and polyacrylic intraocular lenses on posterior capsular opacification 3 years after cataract surgery.",
"The Madurai Intraocular Lens Study. II: Clinical outcomes.",
"Ultrasound biomicroscopy examination of intraocular lens haptic position after phacoemulsification with continuous curvilinear capsulorhexis and extracapsular cataract extraction with linear capsulotomy.",
"Quality of vision after AMO Array multifocal intraocular lens implantation."
] |
[
"To compare the inhibiting effect on posterior capsule opacification (PCO) of a silicone intraocular lens (IOL) with a sharp posterior optic edge (ClariFlex OptiEdge, Advanced Medical Optics) and a silicone IOL with a round optic edge (PhacoFlex SI-40, Advanced Medical Optics). Setting: Department of Ophthalmology, University of Vienna, Vienna, Austria.\n This prospective randomized patient- and examiner-masked study comprised 104 eyes of 52 patients with bilateral age-related cataract. All patients had cataract surgery in both eyes and received a sharp-edged IOL in 1 eye and a round-edged IOL in the other eye. Postoperative examinations were at 1 week, 1 and 6 months, and 1 year. Digital slitlamp and retroillumination images were taken of each eye. The amount of PCO was assessed subjectively at the slitlamp and objectively using Automated Quantification of After-Cataract (AQUA) automated-image analysis software.\n The sharp-edged IOL group had significantly less regeneratory and fibrotic PCO 1 month, 6 months, and 1 year after surgery. The mean AQUA PCO score (scale 0 to 10) was 0.71 in the sharp-edged IOL group and 1.40 in the round-edged IOL group (P<.001). The sharp-edged IOL group had less peripheral fibrotic PCO. There was no significant difference between the 2 IOL groups in patient reports of edge glare.\n The sharp-edged design of the ClariFlex OptiEdge silicone IOL led to significantly less PCO than the round-edged PhacoFlex SI-40 IOL 1 year postoperatively.",
"To examine the influence of intraocular lens (IOL) optic edge design and optic material on fibrosis of the anterior and peripheral posterior capsules and on capsulorhexis contraction.\n Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.\n This randomized controlled patient- and examiner-masked study comprised 210 eyes of 105 patients with bilateral age-related cataract. In Group 1 (n = 53), the Sensar OptiEdge AR40e hydrophobic acrylic IOL with a sharp posterior optic edge was compared with the AR40 acrylic IOL with a round edge. In Group 2 (n = 52), the ClariFlex OptiEdge silicone IOL with a sharp posterior optic edge was compared with the PhacoFlex SI-40 silicone IOL with a round edge All IOLs were manufactured by Advanced Medical Optics, Inc. Standardized digital slitlamp images of anterior capsule opacification (ACO) and fibrotic posterior capsule opacification (PCO) were taken 1 year postoperatively, and digital retroillumination images were taken at 1 week and 1 year. The intensity of fibrotic PCO was graded subjectively (score 0 to 4), ACO was graded objectively (score 0% to 100%), and the capsulorhexis area (mm(2)) was determined objectively.\n One year after surgery, the mean ACO score was 32% in eyes with the sharp-edged acrylic IOL and 29% in eyes with the round-edged acrylic IOL (P<.05). In the silicone group, the mean was 31% and 26%, respectively (P<.05). The mean fibrotic PCO score was lower in eyes with a sharp-edged acrylic IOL than in eyes with a round-edged acrylic IOL (0.26 and 0.93, respectively; P<.05) and in eyes with a sharp-edged silicone IOL than in eyes with a round-edged silicone IOL (0.24 and 0.82, respectively; P<.001). At 1 year, the mean capsulorhexis area was statistically significantly smaller in eyes with a sharp-edged silicone IOL than in eyes with a round-edged silicone IOL (P<.05).\n Acrylic and silicone IOLs with the sharp OptiEdge design led to significantly less fibrotic PCO but more ACO than round-edged acrylic and silicone IOLs. The sharp-edged silicone IOL caused significantly more capsulorhexis contraction than the round-edged silicone IOL and both acrylic IOLs.",
"To compare the degree of posterior capsule opacification (PCO) and visual function in eyes implanted with an acrylic intraocular lens (IOL) with a sharp posterior optic edge with that in eyes implanted with an IOL with a rounded optic edge.\n Randomized clinical trial.\n Seventy-five consecutive patients scheduled for bilateral phacoemulsification were assigned randomly to 1 of 2 groups. One group received an acrylic IOL with a sharp edge (Sensar AR40e, AMO, Santa Ana, CA) in the left eye and an acrylic IOL of the same optic material and loops but with a rounded-edge optic (Sensar AR40) in the right eye. The other group received the sharp-edged IOL in the right eye and the rounded-edge IOL in the left eye. Sixty-nine patients (92%) completed follow-up.\n All patients underwent implantation of a sharp-edged IOL in 1 eye and a rounded-edge IOL in the fellow eye.\n The PCO value of these patients was measured using the Scheimpflug videophotography system at 1, 3, 6, 12, 18, and 24 months after surgery. The incidence of eyes that required a neodymium:yttrium-aluminum-garnet (Nd:YAG) laser posterior capsulotomy was examined. Visual acuity and contrast sensitivity with and without a glare source also were evaluated.\n The mean PCO value in the sharp-edge IOL group was significantly less than that in the rounded-edge IOL group throughout the follow-up period. The incidence of Nd:YAG capsulotomy also was significantly less in the sharp-edge group than in the rounded-edge group (P = 0.0095). No significant difference was found in mean visual acuity during the 24 months of follow-up. However, contrast visual acuity with and without glare was significantly better in the sharp-edge group than in the rounded-edge group at 24 months after surgery.\n The degree of posterior capsule opacification in eyes with an acrylic IOL with a sharp posterior optic edge is significantly less than that in eyes with a rounded-edge IOL, and the sharp-edge optic led to better contrast sensitivity with and without glare.",
"To compare the intensity of capsule opacification with the sharp and the round optic edge variant of an open-loop hydrophobic silicone intraocular lens (IOL).\n Randomized, controlled, double-blind clinical trial with intraindividual comparison.\n Fifty-one patients with bilateral age-related cataract were included (102 eyes). Each patient had had cataract surgery in both eyes and received a Microsil IOL with a sharp optic edge design (model S) in one eye and a Microsil IOL with a round optic edge design (model R) in the fellow eye. Both IOLs had an identical haptic design (nonangulated polymethylmethacrylate) and silicone optic material. The patients were examined at the slit lamp, best-corrected visual acuity was assessed, and standardized high-resolution digital retroillumination images of the posterior capsule were taken 5 years after surgery. The intensity of regeneratory posterior capsule opacification (rPCO), fibrotic PCO (fPCO), and anterior capsule opacification (ACO) was assessed subjectively at the slit lamp, and of rPCO, objectively using automated image analysis software (AQUA). The need for an Nd:YAG laser capsulotomy (Nd:YAG-LCT) was noted.\n The mean AQUA PCO score was 1.2 for the model S and 2.4 for the model R lens (P = .001). The model S lens also led to less peripheral fPCO (P = .003). Concerning ACO, there was no significant difference between both IOL groups (P = .72). Whereas no capsulotomy was required with the model S, four cases (16%) had been performed in the model R group.\n Five years postoperatively, the sharp-edged silicone IOL showed less rPCO and fPCO than the round-edged IOL. However, regarding ACO, there was no significant difference between both IOL styles.",
"To compare the posterior capsule opacification (PCO) inhibiting effect of the sharp posterior optic edge design of the Sensar OptiEdge AR40e intraocular lens (IOL) (Allergan Surgical) with that of the round-edged design of the Sensar AR40 IOL. Setting Department of Ophthalmology, University of Vienna, Vienna, Austria.\n This prospective randomized patient- and examiner-masked study comprised 106 eyes of 53 patients with bilateral age-related cataract. Each patient had cataract surgery in both eyes and received an AR40 IOL in 1 eye and an AR40e IOL in the other eye. Postoperative examinations were at 1 week, 2 and 6 months, and 1 year. Digital slitlamp and digital retroillumination images of each eye were taken. The amount of PCO was assessed subjectively at the slitlamp and objectively using automated image-analysis software.\n The AR40e group had significantly less regeneratory and fibrotic PCO 1 year after surgery. The mean automated image-analysis software PCO score (scale 0 to 10) was 2.19 in the AR40 group and 1.10 in the AR40e group (P <.001). The AR40e group had less peripheral fibrotic PCO. There was no significant difference in patient-reported edge glare between the 2 IOL groups.\n The sharp-edged design of the Sensar OptiEdge AR40e IOL led to significantly less PCO than the round-edged AR40 IOL 1 year postoperatively.",
"Comparison of the intensity of posterior capsule opacification (PCO) between a silicone intraocular lens (IOL) and a hydrophobic acrylic IOL, both of them 3-piece and open-loop and having truncated optics with sharp edges.\n Randomized, controlled, patient- and examiner-masked trial with intrapatient comparison.\n One hundred six eyes of 53 patients with age-related bilateral cataract.\n Each patient had cataract surgery in both eyes and received a silicone IOL in one eye and a hydrophobic acrylic IOL in the fellow eye. Follow-up examinations were at 1 and 3 years after surgery. The patients were examined at the slit lamp, visual acuity (VA) was assessed, and standardized high-resolution digital retroillumination images of the posterior capsule were taken. The amount of PCO was assessed subjectively at the slit lamp and objectively using automated image analysis software. Data of 56 eyes of 28 patients, who were examined at each follow-up, were analyzed.\n Posterior capsule opacification intensity at 3 years as measured with automated image analysis.\n At 1 and 3 years after surgery, PCO did not differ between the silicone (1.6 and 1.9 [image analysis scores, 0-10 scale], respectively) and acrylic IOLs (1.7 and 2.2) (P > 0.24). Furthermore, there was no significant difference in best-corrected VA, rhexis/IOL overlap, capsular folds, and amount of anterior capsule opacification during the follow-up period. In each group, one neodymium:yttrium-aluminum-garnet (YAG) laser capsulotomy was performed during the entire study duration.\n Silicone and hydrophobic acrylic are similarly effective in inducing the PCO-inhibiting effect of a rectangular, sharp optic edge. Three years after surgery, the PCO intensity and the YAG rate were low with both IOL models.",
"To evaluate the role of posterior optic edge design and the effect of anterior capsule polishing on peripheral fibrotic posterior capsule opacification (PCO).\n Department of Ophthalmology, University of Vienna, Vienna, Austria.\n This randomized prospective study comprised 144 eyes of 72 patients with bilateral age-related cataract. Each patient had standardized cataract surgery in both eyes by the same surgeon. Group 1 (46 patients) received a round-edged hydrophobic acrylic IOL (AMO Sensar AR40) in 1 eye and a sharp-edged hydrophobic acrylic IOL (AMO Sensar OptiEdge AR40e) in the other eye. Group 2 (26 patients) received a silicone IOL (Pharmacia CeeOn 911A) with a truncated optic in both eyes. In this group, the anterior capsule was extensively polished in 1 eye and was left unpolished in the other eye. Digital slitlamp photographs were taken 1 year postoperatively using a standardized photographic technique for fibrotic PCO. The intensity of PCO was subjectively graded (score 0 to 4) by 2 masked examiners.\n Subjective PCO scores correlated well between the 2 examiners (r = 0.88). In Group 1, the mean PCO score was 0.26 for the OptiEdge AR40e IOL and 0.90 for the AR40 IOL (P<.01). In Group 2, the mean PCO score was 0.24 in eyes with a polished capsule and 0.17 in eyes in which the capsule was not polished (P =.31).\n The sharp-edged OptiEdge AR40e IOL led to significantly less peripheral fibrotic PCO 1 year postoperatively than the round-edged AR40 IOL. In eyes with the sharp-edged silicone 911A IOL, anterior capsule polishing caused no significant difference in fibrotic PCO.",
"To evaluate the relationship of the anterior capsule and the AcrySof MA30BA intraocular lens (IOL) and its impact on the development of central posterior capsule opacification (PCO).\n Prospective, randomized, controlled trial.\n Two hundred two patients with senile cataracts received an AcrySof IOL between July and December 1998 at Iladevi Cataract and IOL Research Center, Ahmedabad, India.\n Patients were randomized prospectively to receive 1 of the 3 possibilities of anterior capsule and IOL optic relationship: group 1, total anterior capsule cover (360 degrees ) of the optic; group 2, no anterior capsule cover (360 degrees ) of the optic; group 3, partial anterior capsule cover (<360 degrees ) of the optic. After surgery, slit-lamp video photography was performed every 6 months for 3 years. Analyses of variance and chi-square tests were used to compare treatment groups.\n Incidence of PCO in the 3 groups. The posterior capsule was divided into 3 zones: peripheral, central 3 mm, and midperipheral (the space between the peripheral and the central zones).\n The average follow-up was 35.3 +/- 1.52 months in all the groups. At 3 years, the rate of central PCO was 6.4% in group 1, 7.1% in group 2, and 5.9% in group 3 (P = 0.9). Midperipheral PCO was present in 24.2% in group 1, 16% in group 2, and 20.6% in group 3 (P = 0.9). Peripheral PCO was seen in 100% of patients in all groups. The neodynium:yttrium-aluminum-garnet laser (Nd:YAG) posterior capsulotomy rate was 0% in all groups.\n There was no significant difference in the incidence of development of central PCO among the 3 groups. No patient experienced central PCO that required Nd:YAG capsulotomy. When using the AcrySof IOL model MA30BA, the relationship of the anterior capsule and the IOL does not seem to be a factor that relates to the development of central PCO.",
"To compare posterior capsule opacification (PCO) after cataract surgery with implantation of two silicone intraocular lenses (IOLs) with different designs.\n We carried out a prospective, clinical study of 116 patients randomized to standardized phacoemulsification with implantation of CeeOn Edge (n = 57) or SI40NB (n = 59) IOLs. The follow-up period was 3 years. To evaluate PCO morphologically, digital images were obtained and analysed using evaluation of posterior capsule opacification computer software (epco). The neodymium:YAG (Nd:YAG) capsulotomy rate was recorded.\n At 2 and 3 years, the eyes with SI40NB IOLs had significantly more PCO than those with the CeeOn Edge IOLs (p = 0.00014 and p = 0.002). Nine Nd:YAG capsulotomies were performed in the SI40NB group and none in the CeeOn Edge group. This difference was statistically significant (p = 0.003). In some patients a regression of PCO was noticed and confirmed using epco. Statistically less PCO was noted when the capsulorhexis rim was placed so that it covered all 360 degrees of the optic of the IOL.\n A clinically and statistically significant difference in PCO development between CeeOn Edge and SI40NB IOLs at 2 and 3 years postoperatively was found. These findings support earlier studies indicating that a sharp edge of the optic is a more important factor in IOL design than IOL material in the prevention of PCO.",
"To compare the posterior capsule opacification (PCO) inhibiting effect of the sharp posterior optic edge design of the Sensar OptiEdge AR40e intraocular lens (IOL) with that of the double-round edge design of the Sensar AR40 IOL over a period of 3 years.\n Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.\n Fifty-three patients with bilateral age-related cataract (106 eyes) were included in this randomized prospective bilateral patient- and examiner-masked clinical trial with intraindividual comparison. Each study patient had cataract surgery in both eyes and received a Sensar AR40 IOL (anterior and posterior round optic edges) in 1 eye and a Sensar OptiEdge AR40e IOL (round anterior and sharp posterior optic edge) in the other eye. Follow-up examinations were at 1 week, 1 and 6 months, and 1, 2, and 3 years. Digital retroillumination images were taken of each eye. The amount of PCO was assessed subjectively at the slitlamp and objectively using automated image-analysis software (AQUA) 1, 2, and 3 years after surgery.\n The sharp-edged AR40e lens showed significantly less regeneratory and fibrotic PCO 1, 2, and 3 years after surgery. The mean AQUA PCO score was 2.18 for the AR40 and 1.00 for the AR40e lens after 1 year; 2.94 and 1.56 after 2 years, and estimated at 3.13 and 1.77, respectively, after 3 years (scale 0 to 10; P<.001). The neodymium:YAG laser capsulotomy rate was significantly higher in the AR40 group. The AR40e lens also led to less peripheral fibrotic PCO. There was no significant difference in complaints concerning edge glare between the groups.\n Compared with the AR40 IOL, the sharp posterior optic edge design of the Sensar OptiEdge AR40e IOL led to significantly less PCO 1, 2, and 3 years postoperatively. In contrast with most past studies on PCO-preventative factors, this study varied only 1 parameter, namely the optic edge design, and the main outcome measure (PCO) was assessed with an objective image-analysis system.",
"To compare the posterior capsule opacification (PCO) inhibiting effect of a 3-piece polymethyl methacrylate (PMMA) intraocular lens (IOL) with a sharp optic edge design with that of the round-edged version of the same IOL during a 5-year period.\n Randomized patient- and examiner-masked clinical trial with intraindividual comparison.\n Thirty-two patients with bilateral age-related cataract (64 eyes).\n Each study patient had phacoemulsification cataract surgery in both eyes and received a sharp optic edge PMMA IOL in one eye and a round optic edge PMMA IOL in the fellow eye (both by Dr Schmidt in Germany). Follow-up examinations were at 1 week, 1 month, 1 year, 3 years, and 5 years. Digital retroillumination images were taken from each eye. The amount of posterior capsule opacification was assessed objectively by means of automated image analysis software (Automated Quantification of After-Cataract) at 1 year, 3 years, and 5 years after surgery.\n Posterior capsule opacification score: 0-10.\n The sharp optic edge IOL showed significantly less regeneratory and fibrotic PCO at 1 year, 3 years, and 5 years after surgery. The mean AQUA PCO score was 5.12 for the round-edge and 2.49 for the sharp-edge IOL (scale, 0-10; P<0.001) at 5 years. The mean difference among patients for the PCO score in the eye implanted with the sharp optic edge versus the score in the eye with the round optic edge was 2.83 at 5 years (95% confidence interval, 1.66-4.00). Due to the large number of neodymium:yttrium-aluminum-garnet laser capsulotomies that were performed (12 in the round-edge group and 4 in the sharp-edge group), there was no significant difference in visual acuity between both groups at any time point.\n Compared with the round-edge version, the sharp optic edge design of a 3-piece PMMA IOL led to significantly less PCO at 1 year, 3 years, and 5 years after surgery. However, the sharp optic edge did not lead to complete PCO prevention during this follow-up period. This finding has implications for the design of PMMA IOLs used for cataract surgery, especially in the developing world.",
"To evaluate the differences in posterior capsule opacification (PCO) and visual and optical performance between a microincision intraocular lens (IOL) and a conventional IOL.\n Ophthalmology Department, St. Thomas' Hospital, London, United Kingdom.\n Patients with bilateral cataract were prospectively randomized to receive a HumanOptics MC611MI microincision IOL (microlens group) or an Alcon AcrySof MA60AC 3-piece IOL (control group) in either eye and were followed for 24 months. Best corrected visual acuity (BCVA) (logMAR) was measured; PCO was quantified by POCO software analysis of retroillumination images. Aberrations and modulation transfer function (MTF) were measured at the 24-month visit.\n The study enrolled 32 patients. The mean percentage area PCO was greater in the microlens group than in the control group from 3 months onward and was statistically significant from 12 months onward. The greatest difference in PCO between groups was at 24 months: mean 25.45%+/-34.51% (SD) in the microlens group versus 7.82%+/-13.35% in the control group (P= .029). The BCVA in the control group was slightly better at all time points; the difference between groups was statistically significant at 3, 6, and 12 months. No significant difference in aberrations was detected. The MTF curves were comparable for both IOLs.\n Both IOLs provided good visual performance. There was no evidence of distortion of the microincision IOL in the capsular bag. The microincision IOL had poorer PCO performance, which was visually significant and was caused by migration of lens epithelial cells through its broad optic-haptic junctions.",
"To evaluate the development of posterior capsule opacification (PCO) in patients implanted with 5.5 mm optics, single-piece or three-piece acrylic intraocular lens (IOL) in cataract surgery prospectively.\n This study was carried out on 267 eyes of 249 patients implanted with three-piece, 5.5 mm optics, acrylic IOL and 252 eyes of 244 patients implanted with single-piece, 5.5 mm optics, acrylic IOL by phacoemulsification technique between September 2001 and February 2003. A total of 519 eyes of 493 patients were prospectively evaluated for PCO development during the 25-month period. All the patients were analyzed periodically with anterior segment retroillumination photography. The data provided were analyzed with chi-square method.\n The results between the two groups for PCO development were not statistically significant. However, there was a prominent opacification of the posterior capsule where the optic and haptic junction of IOL was positioned in some patients implanted with single-piece IOL. During the follow-up period, no patients implanted with either three-piece or single-piece acrylic IOL required Nd:YAG laser capsulotomy.\n Biocompatibility and reduced rate of PCO development are among the leading features of new generation IOLs. The intracapsular implantation of 5.5 mm optics acrylic IOLs resulted in decreased incidence of PCO and therefore greater patient satisfaction. Further studies investigating the effects of IOL optics, haptic structure and length, capsulorrhexis size, and IOL material and design features on PCO development will clarify the subject.",
"To evaluate the long-term effects of anterior capsule polishing on regeneratory posterior capsule opacification (PCO), anterior capsule opacification (ACO), and fibrotic PCO with a silicone intraocular lens (IOL) with sharp optic edges.\n Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.\n This prospective bilateral randomized patient- and examiner-masked clinical trial comprised 130 eyes of 65 patients with bilateral age-related cataract. All eyes had implantation of a 3-piece silicone IOL with a truncated, sharp-edged optic (CeeOn Edge 911A, Advanced Medical Optics). In 1 eye, the anterior capsule was extensively polished using an aspiration curette after phacoemulsification and cortex aspiration. Regenerative PCO was quantified objectively, while ACO and fibrotic PCO were graded subjectively 1, 2, 3, and 5 years postoperatively.\n The mean ACO score was significantly lower in the eyes in which the anterior capsule had been polished (1 year, P<.02; 2 years, P<.03; 3 years, P<.01; 5 years, P<.01). The mean difference in regeneratory PCO and fibrotic PCO scores between the 2 groups was not statistically significant.\n Three years after cataract surgery, eyes in which the anterior capsule had been polished had significantly less ACO. However, polishing did not lower PCO intensity when a sharp-edged CeeOn 911A IOL was implanted in the bag. Although results indicate that anterior capsule polishing may enhance the development of regeneratory PCO, this trend did not reach statistical significance.",
"To compare the rates and morphologic features of posterior capsule opacification (PCO) after small-incision phacoemulsification and in-the-bag implantation of 2 foldable intraocular lenses (IOLs) over an 18-month follow-up.\n Departments of Ophthalmology, Hospital of Conegliano, Conegliano, and Maggiore Hospital of Bologna, Bologna, Italy.\n In an open clinical study, 78 cataract patients were randomly selected to have implantation of a silicone CeeOn Edge (Pharmacia) or acrylate AcrySof (Alcon) IOL after phacoemulsification cataract surgery. All the patients were operated on using a standard technique and in-the-bag IOL implantation. One eye in each patient was studied. Morphologic evaluation of PCO was performed using Evaluation of Posterior Capsule Opacification software.\n At 18 months in the CeeOn Edge group, 36 eyes (90%) had a clear posterior capsule and 4 (10%) had PCO that did not affect visual acuity. In the AcrySof group, 26 eyes (68%) had a clear posterior capsule, 11 (29%) had PCO that did not affect visual acuity, and 1 (3%) had PCO with a decrease of 2 or more lines of visual acuity that required a neodymium:YAG laser capsulotomy. No eye developed Elschnig pearls or stretched folds in the bag. The postoperative best corrected visual acuity ranged from 0.8 to 1.0 in 96% in the CeeOn Edge group and in 92% in the AcrySof group. No IOL haze or discoloration was observed in the CeeOn Edge group. Mild IOL decentration and tilting occurred in 4 AcrySof eyes; however, no glistenings were found any AcrySof IOL.\n Both the CeeOn Edge and AcrySof groups had a low incidence of PCO after an 18-month follow-up. The CeeOn Edge group had significantly less PCO than the AcrySof group. These results confirm that IOLs with square truncated edges create a barrier effect at the optic edge, reducing the overall incidence of PCO.",
"To evaluate whether the position of the anterior continuous curvilinear capsulorhexis influences the rate of posterior capsule opacification (PCO).\n A total of 119 patients, aged 61-86 years, underwent cataract surgery with phacoemulsification performed by a single surgeon. The patients were randomized to implantation with either a silicone intraocular lens (IOL) (SI40NB, Allergan) or an AcrySof IOL (MA60BM, Alcon). Three years after surgery, the rate of PCO was analysed using the evaluation of posterior capsule opacification computer software (EPCO). The results were related to the capsulorhexis position, which was assessed with a retroillumination photograph.\n If the capsulorhexis was located partially or completely off the optics of the IOL, compared to totally on the IOL, significantly more PCO was found (p = 0.0014). When comparing within each IOL type, patients with AcrySof IOLs were found to have significantly less PCO when the capsulorhexis was totally on the optic (p = 0.0048). This difference was also significant in the silicone group (p = 0.041).\n A relatively small and central capsulorhexis allowing for the complete covering of the IOL optics by the rhexis edges seems to protect against PCO in cataract surgery, with both round-edged silicone IOLs and sharp-edged hydrophobic acrylic IOLs.",
"Posterior capsule opacification (PCO) is still a major long-term complication of modern cataract surgery. We evaluated the impact of sharp-edged intraocular lenses (IOLs) with different haptic designs made from the same hydrophobic acrylic material on posterior and anterior lens capsule opacification.\n Eye clinic of Kaunas University of Medicine, Lithuania. Prospective randomised clinical study.\n Seventy-four eyes of 74 patients scheduled for cataract surgery were included in a prospective randomised clinical study. Thirty-seven eyes of 37 patients received a three-piece acrylic hydrophobic (AcrySof, MA3OBA, Alcon) IOL; and thirty-seven eyes of 37 patients received a one-piece acrylic hydrophobic (AcrySof, SA3OAL, Alcon) IOL. Visual acuity, anterior capsule opacification (ACO), capsular folds, capsulorrhexis/optic overlapping and posterior capsule opacification (PCO) were evaluated. ACO was assessed subjectively. PCO values in the entire IOL optic area and in the central 3 mm optic zone were assessed using a photographic image-analysis system (EPCO2000). Follow-ups were performed postoperatively at 1 day, 6 months, 1 year and 2 years.\n There were no significant differences in best corrected visual acuity, grade of ACO and capsulorrhexis/optic overlapping between IOL types during the follow-up period. Patients in the one-piece acrylic hydrophobic IOL group more frequently presented with capsular folds behind the IOL optic area than those in the three-piece IOL group. In the three-piece acrylic hydrophobic IOL group, PCO values (mean (SD)) of the entire IOL optic area were significantly lower six months postoperative (three-piece: 0.002 (0.009); one-piece: 0.007 (0.017); p=0.04), one year postoperative (three-piece: 0.004 (0.016); one-piece: 0.026 (0.041); p=0.001) as well as one year postoperative in the central 3 mm optic zone (three-piece: 0.000 (0.0002); one-piece: 0.019 (0.049); p=0.001). However, two years postoperative, the PCO values of the groups did not show significant differences (entire IOL optic area: three-piece, 0.136 (0.223); one-piece, 0.154 (0.190); p=0.18; central zone: three-piece, 0.023 (0.065); one-piece: 0.020 (0.039); p=0.44).\n The 2 year follow-up after cataract surgery showed no significant difference in ACO and PCO development between three-piece and one-piece acrylic hydrophobic intraocular lenses.",
"To compare the posterior capsule opacification (PCO) inhibiting effect of the round anterior and sharp posterior optic edge profile of the Clariflex silicone intraocular lens (IOL) [AMO Inc, Santa Ana, California, USA] with that of the double-round edge profile of the SI40 (Phacoflex; AMO Inc, Santa Ana, California, USA) silicone IOL over a period of three years.\n Prospective, randomized, double-masked, bilateral clinical trial.\n The study took place at the Department of Ophthalmology, Medical University of Vienna, Austria. Fifty-two patients with age-related cataracts (104 eyes) were included in the study. Each patient received an SI40 IOL (round edges) in one eye and a Clariflex IOL with OptiEdge (sharp posterior optic edge) in the other eye. Follow-up examinations were at one week, one month, six months, and one, two, and three years. Digital retroillumination images were taken of each eye. The amount of PCO was subjectively assessed with the slit-lamp and objectively assessed by automated image analysis software (the computer program Automated Quantification of After-Cataract [AQUA]; Vienna, Austria) one, two, and three years after surgery.\n The Clariflex lens showed markedly less PCO at one, two, and three years after surgery. The mean AQUA PCO score was 1.39 for the SI40 and 0.56 for the Clariflex lens after one year, estimated at 1.64 and 0.57 after two years, and at 2.04 and 0.64, respectively, after three years (scale zero to 10; P < .001). The Nd:YAG laser capsulotomy rate was far higher in the SI40 group (Five cases vs one case at three years).\n The sharp posterior optic edge profile of the Clariflex silicone IOL led to marked and consistently less PCO than the round-edged SI40 IOL one, two, and three years after surgery.",
"To examine the influence of optic material on posterior capsule opacification (PCO) by comparing PCO and visual functions between eyes with an acrylic intraocular lens (IOLs) and those with a silicone IOL of the same optic design and with the same haptics.\n Randomized clinical trial.\n One hundred patients scheduled for phacoemulsification surgery underwent implantation of an acrylic IOL (AMO Sensar; AR40e) in one eye and implantation of a silicone IOL (ClariFlex) of the same optic design and loops in the fellow eye. Eighty-nine patients (89%) remained for analysis. The PCO value was measured using the Scheimpflug videophotography system at one, three, six, 12, 18, 24, 30, and 36 months postoperatively. The incidence of eyes that required a neodymium:yttrium-aluminum-garnet (Nd:YAG) laser capsulotomy was examined; visual acuity and contrast sensitivity with and without a glare source were also evaluated.\n The mean PCO value did not increase significantly during follow-up in either the acrylic or silicone IOL group. When comparing the groups, no statistically significant difference was found in the PCO or in the incidence of Nd:YAG capsulotomy, although both tended to be slightly better in the silicone group than in the acrylic group. There was also no significant difference between the groups in visual acuity or in photopic and mesopic contrast sensitivity with or without glare.\n When acrylic and silicone IOLs are of the same optic design and with the same haptics, the optic material does not influence the development of PCO enough to impair visual function.",
"To compare intensity of posterior capsule opacification (PCO) between the 1-piece and 3-piece haptic designs of an open-loop hydrophobic acrylic intraocular lens (IOL).\n A randomized, patient- and examiner-masked clinical trial with intraindividual comparison.\n Fifty-two patients with bilateral age-related cataract (104 eyes).\n Each patient had cataract surgery in both eyes and received a 1-piece Acrysof IOL in one eye and a 3-piece Acrysof IOL in the fellow eye. Follow-up examinations were at 1 week, 1 month, 6 months, 1 year, and 2 years. Patients were examined at the slit lamp, visual acuity (VA) was determined, and standardized high-resolution digital retroillumination images of the posterior capsule were taken. The intensity of PCO was assessed subjectively at the slit lamp and objectively using automated image analysis software.\n Posterior capsule opacification score (scale, 0-10).\n There was no significant difference between IOL styles in best-corrected VA, rhexis/IOL overlap, capsular folds, and amount of anterior capsule opacification during the follow-up period. One year postoperatively, the amount of regeneratory PCO was higher for the 1-piece Acrysof eyes (image analysis software score: 1.3) than for the 3-piece Acrysof eyes (score: 0.9; P = 0.002). However, 2 years postoperatively, there was no significant difference between the 2 IOL styles (1-piece: 1.5; 3-piece: 1.3; P = 0.3). Neodymium:yttrium-aluminum-garnet capsulotomy was not performed in the study.\n One year postoperatively, the 1-piece Acrysof showed slightly more regeneratory PCO than the 3-piece Acrysof. However, 2 years postoperatively, the barrier effect of the 1-piece design was comparable to that of the 3-piece haptic design, with low PCO intensity.",
"To compare posterior capsule opacification (PCO) after cataract surgery with implantation of 3 intraocular lenses (IOLs) of different materials and design.\n St. Erik's Eye Hospital, Stockholm, Sweden.\n In this prospective clinical study, 180 patients had standardized phacoemulsification performed by a single surgeon and were randomized to have implantation of a heparin-surface-modified (HSM) poly(methyl methacrylate) (PMMA) IOL (809C, Pharmacia & Upjohn), a silicone IOL (SI-40NB, Allergan), or an acrylic IOL (AcrySof MA60BM, Alcon). To morphologically evaluate PCO, retroillumination photographs were obtained and analyzed using Evaluation of Posterior Capsule Opacification computer software. The neodymium:YAG (Nd:YAG) capsulotomy rate was recorded.\n After 2 years, the HSM PMMA IOL group had significantly more PCO than the silicone and AcrySof IOL groups; the silicone group had significantly more PCO than the AcrySof group (P<.05). The Nd:YAG capsulotomy rate was 20% in the HSM PMMA group, 22% in the silicone group, and 8% in the AcrySof group.\n Patients with an AcrySof IOL developed significantly less PCO than those with a silicone or HSM PMMA IOL with a round-edged design.",
"To determine the effect of intraocular lens (IOL) material on the development of posterior capsule opacification (PCO) at 1 year.\n Department of Ophthalmology, St. Thomas' Hospital, London, United Kingdom.\n One hundred six eyes of 53 patients with bilateral cataract and no other ocular comorbidity were prospectively randomized to receive a hydrophobic acrylic or hydrophilic acrylic single-piece IOL in the first eye to have surgery. The alternate IOL was implanted in the fellow eye 4 to 6 weeks later. All surgery was performed by a single surgeon. Postoperative follow-up was 1 day, 1 and 6 months, and 1 year. At each visit, the best corrected high- and low-contrast visual acuities were assessed and a high-intensity digital retroillumination photograph was taken. Posterior capsule opacification was assessed from the digital images by a single operator using a dedicated software program and calculated as the percentage area of opacified capsule.\n One year postoperatively, the median percentage area of PCO was 50.3% in the hydrophilic IOL group and 4.9% in the hydrophobic IOL group (P<.001). The difference in PCO was not accounted for by loss of contact between the capsulorhexis and IOL surface. Further analysis showed that lens epithelial cells tended to invade the posterior capsule at the haptic-optic junction. This was more marked in the hydrophilic IOL group.\n The rate of PCO was significantly higher with the hydrophilic IOL. However, the results cannot be attributed to the IOL material alone as they show the importance of both IOL material and design.",
"At the Department of Ophthalmology, Heidelberg, Germany, posterior capsule opacification (PCO) of a silicone and an acrylic intraocular lens (IOL) with a sharp optic edge design was evaluated.\n In a prospective study either the AMO ClariFlex silicone IOL or the Sensar AR40e hydrophobic acrylic IOL were implanted in 47 patients following uneventful phacoemulsification. Mean patient age was 76.2+/-7.8 (ClariFlex) and 73.4+/-12.9 years (AR40e), respectively. The mean follow-up time was 19.7+/-5.34 in the ClariFlex and 21.9+/-1.89 months in the AR40e group. PCO development was evaluated postoperatively using the EPCO 2000 analysis software (scale 0-4). Areas of interest were the total IOL optic, the central 3-mm zone as well as the capsulorhexis.\n In both groups, all patients achieved a BCVA of 20/32 (AR40e) and 20/25 (ClariFlex), respectively. There was a very low incidence of PCO development with a mean EPCO score of 0.07+/-0.2 (ClariFlex and 0.15+/-0.2 (AR40e). Within the 3-mm zone and the capsulorhexis, there was a tendency for even lower EPCO scores in both groups. We calculated a statistically significant difference for the two lens materials for all investigated IOL areas (Wilcoxon's test, p<0.05).\n Both IOLs with a sharp edge design showed good functional results, a stable position in the capsular bag as well as a low incidence of PCO development. However, the silicone IOL showed statistically significantly lower PCO scores.",
"To compare the difference in posterior capsular opacification (PCO) between highly refractive silicone and hydrophobic acrylic foldable intraocular lenses (IOLs) with sharp and round edge designs 3 years after in-the-bag IOL implantation in subjects undergoing bilateral cataract surgery.\n Open-label, prospective, randomized, multicenter clinical trial.\n Two hundred and eighty-eight patients with bilateral surgery for senile cataract operated in German university clinics, eye hospitals, and private ophthalmic surgical centers (Aachen, Ahaus, Bad Hersfeld, Frankfurt/Main, Jena, Rosenheim, and Sulzbach/Saar).\n At each center, a highly refractive index silicone IOL with a sharp optic edge (CeeOn) was intraindividually compared either with a high-refractive index silicone IOL with a round optic edge (PhacoFlex) in 108 patients or with an acrylic IOL with a sharp optic edge (AcrySof) in 139 patients. All patients received standard phacoemulsification with IOL implantation in the bag in both eyes from the same surgeon. A morphological evaluation of PCO was performed by the Evaluation of the Posterior Capsule Opacification (EPCO) system 1 to 2 weeks and 11 to 14 and 35 to 37 months after surgery. The blinded digital pictures were evaluated by an independent investigator. Posterior capsular opacification was statistically evaluated by paired comparisons of 3-year cumulative incidences of neodymium:yttrium-aluminum-garnet (Nd:YAG) laser treatment and EPCO scores.\n Posterior capsular opacification.\n The 3-year cumulative incidences of Nd:YAG laser capsulotomy were 2.1% (CeeOn), compared with 2.1% (AcrySof) (risk difference, 0%; 90% confidence interval, -3.4% to 3.4%), and 5.7% (CeeOn), compared with 17.0% (PhacoFlex) (risk difference, -11.4%; 90% confidence interval, -18.1% to -4.7%). In patients without Nd:YAG laser treatment, medians of the total area EPCO score were 0.0005 (CeeOn) versus 0.0440 (AcrySof) and 0 (CeeOn) versus 0.0700 (PhacoFlex) at 3 years. Functional results, safety, and handling did not significantly differ for the 3 lenses.\n Our results suggest that modern foldable IOLs have a low incidence of PCO after 3 years. There is less PCO for sharp optic edge designs independent of IOL material.",
"To compare the performance of single-piece acrylic vspoly (methylmethacrylate) intraocular lenses (IOL) on the development of posterior capsule opacification (PCO) after conventional extra capsular cataract extraction (ECCE).\n One hundred and eighty-two eyes of 91 patients with bilateral senile cataract undergoing ECCE were prospectively randomized to receive a single-piece Alcon AcrySof SA60AT IOL or a single-piece EPOCH polymethylmethacrylate IOL in the first eye to have surgery. At 1, 6 and 12 months post-operative follow-up, digital retro illumination images of the posterior capsule were taken for PCO assessment semi-objectively using PCO (POCO automated analysis software) system. Relationship of anterior capsule contact (total off and partial cover) on optic for PCO was analyzed.\n The AcrySof IOL was associated with less PCO than EPOCH lens at 6 months (10.01+/-8.75% vs 32.26+/-27.44%; P<0.001) and 1-year (11.65+/-10.55% vs 38.38+/-29.62%; P<0.001) follow-up. The EPOCH IOL showed a remarkably significant difference on development of PCO with anterior capsule overlap on IOL optic (total off and part on) 1 year (P<0.039), whereas no such difference was observed with the AcrySof IOL (P=0.197).\n The AcrySof IOL led to significantly less PCO than the EPOCH IOL post-operatively after extracapsular cataract extraction.",
"To perform an intraindividual comparison of posterior capsule opacification (PCO) with 2 foldable intraocular lenses (IOLs) and a foldable acrylic IOL 1 year after in-the-bag implantation.\n Seven German ophthalmology centers.\n In an open prospective randomized multicenter study, each center intraindividually compared a high-refractive-index, sharp-edged optic silicone IOL (CeeOn Edge 911A, Pharmacia) with a high-refractive-index, round-edged optic silicone IOL (PhacoFlex SI-40NB, Allergan) or a sharp-edged optic acrylic IOL (AcrySof MA60BM, Alcon). Of 288 randomized patients, 247 had standard phacoemulsification with in-the-bag IOL implantation in both eyes by the same surgeon. One eye of each patient received a CeeOn Edge IOL and the fellow eye, an AcrySof or PhacoFlex IOL. A morphologic evaluation of PCO was performed using the Evaluation of Posterior Capsule Opacification (EPCO) system 1 to 2 weeks and 11 to 14 months after surgery. The digital pictures were evaluated by an independent investigator who was blind to the type of IOL. Intraindividual differences in EPCO scores were statistically evaluated by a 1-sided binomial test at an alpha-level of 5%.\n One year after surgery, 127 patients with the AcrySof IOL and 102 patients with the PhacoFlex IOL in the control eye were reexamined. Functional results, safety, and handling were not significantly different between the 3 IOLs. All reexamined eyes had a very low PCO grade. The EPCO values revealed less PCO in eyes with the CeeOn Edge IOL than in eyes with the AcrySof or PhacoFlex IOL, but the difference was not statistically significant. A neodymium:YAG laser capsulotomy was performed in 1 eye with a CeeOn Edge IOL, 1 eye with an AcrySof IOL, and 2 eyes with a PhacoFlex IOL.\n The EPCO PCO grade was low 1 year after implantation of CeeOn Edge 911A, PhacoFlex SI-40NB, and AcrySof MA60BM IOLs; there was no statistically significant difference between the IOLs. The impact of IOL material and edge design on PCO development might be relevant in a long-term follow-up of this study.",
"To evaluate the effect of 1-piece and 3-piece hydrophobic acrylic intraocular lenses (IOLs) on posterior capsule opacification (PCO) after cataract surgery.\n Ophthalmology departments of 3 hospitals in the United Kingdom and Germany and the Department of Physics at a United Kingdom university.\n A series of 131 patients having cataract surgery had implantation of an acrylic 1-piece (SA30AL) or an acrylic 3-piece (MA30BA) IOL (AcrySof, Alcon). Surgery was performed according to standardized protocol by a single surgeon at each hospital. Posterior capsule opacification was assessed using digital retroillumination photography. All images were analyzed at a single center according to a standard protocol. Data were analyzed 6 months and 1 year after surgery.\n There was no statistically significant difference in the percentage area of PCO between the 1-piece (mean 16.0% +/- 15.7% [SD]) and 3-piece (mean 13.6% +/- 19.8%) cohorts 6 months and 1 year after surgery (P =.0664).\n There was no evidence of a difference in the area of PCO after cataract surgery between 1-piece and 3-piece IOLs, which were otherwise matched for material and lens geometry.",
"To compare posterior capsular opacification in eyes with IOL of two different materials--silicone or acrylic.\n Eighty consecutive eyes undergoing cataract surgery were prospectively randomized in two groups, 40 eyes receiving a silicone (Sl--30NB) and 40 eyes an acrylic (Acrysof MA60BM) intraocular lens (IOL). The same surgeon performed phacoemulsification and the intraocular lens (PHACO IOL) operation in all cases. Patients were re-examined on the first postoperative day, after one week, four months, and 1-2.4 years. Seven eyes were lost to late control.\n Clinically significant posterior capsular opacification (PCO) (including eyes with capsulotomy already performed) was equally common in both groups; 25% in the silicone group and 19% in the acrylic group (p=0.53). The posterior capsule remained clear in 61% of the silicone and 76% of the acrylic IOL eyes (p=0.18). In the whole study group, 29% of eyes with and 14% without concurrent ocular diseases had significant PCO (p=0.13). In the silicone IOL group, PCO was more common in eyes with concurrent ocular diseases (44%) than eyes without other diseases (10%) (p=0.049). Eyes with acrylic IOL showed no difference in significant PCO, with or without other diseases (18% and 20%, respectively).\n In a consecutive series of 80 cataract eyes central PCO was equally common in eyes receiving a silicone or an acrylic IOL. In the silicone IOL group, however, significant PCO was more common if there was concurrent ocular disease, while with the acrylic IOL concurrent ocular disease did not seem to increase the risk of PCO.",
"To evaluate the effect of hydrophilic and hydrophobic single-piece acrylic intraocular lenses (IOLs) on posterior capsule opacification (PCO) after cataract surgery.\n St. Erik's Eye Hospital, Stockholm, Sweden.\n In a prospective study, 120 patients having cataract surgery were randomized to implantation of a hydrophilic acrylic IOL (BL27, Bausch & Lomb) or a hydrophobic acrylic IOL (AcrySof SA60AT, Alcon). Surgery was performed according to a standardized protocol by 1 of 3 surgeons. Best corrected visual acuity, contrast sensitivity, glare, intraocular pressure, and flare were measured 1 week, 3 months, and 1 year after surgery. Posterior capsule opacification was assessed by digital retroillumination photography and analysis using POCOman software at 1 year. The rate of neodymium:YAG (Nd:YAG) capsulotomy for each IOL was also recorded.\n At 1 year, the hydrophilic acrylic IOL group had a significantly greater percentage area and severity of PCO than the hydrophobic acrylic IOL group (P<.001). Two patients in the hydrophilic acrylic IOL group and 4 in the hydrophobic acrylic IOL group had an Nd:YAG capsulotomy within the first year (P>.05). Contrast sensitivity was significantly better in the hydrophilic acrylic group at 3 months (P<.05); however, at 12 months no difference between the IOLs was observed. There was no significant difference in the other measured parameters.\n Patients with the hydrophilic acrylic BL27 IOL had a significantly greater percentage area and severity of PCO than those with the hydrophobic acrylic SA60AT IOL 1 year after surgery.",
"To compare the degree of posterior capsule opacification (PCO) in eyes with a hydrophilic hydrogel intraocular lens (IOL) with that in eyes with a hydrophobic acrylic IOL.\n Ninety five patients underwent a hydrogel IOL implantation in one eye and an acrylic IOL implantation in the opposite eye. The PCO value of these patients was measured using the Scheimpflug videophotography system at 1, 6, 12, 18, and 24 months postoperatively. The rate of neodymium:YAG (Nd:YAG) laser posterior capsulotomy and visual acuity were also evaluated.\n The mean PCO value in the hydrogel group increased significantly (p<0.0001), while that in the acrylic group did not show significant change. The PCO value in the hydrogel group was significantly greater than that in the acrylic group throughout the follow up period. Kaplan-Meier survival analysis determined that the Nd:YAG capsulotomy rate in the hydrogel group was significantly higher than that in the acrylic group (p<0.0001). Mean visual acuity in the hydrogel group decreased significantly with time (p<0.0001), and became significantly worse than that in the acrylic group at 18 and 24 months postoperatively.\n Posterior capsule opacification in eyes with a hydrophilic hydrogel IOL is significantly more extensive than that in eyes with a hydrophobic acrylic IOL, and results in a significant impairment of visual acuity.",
"To compare the intensity of posterior capsule opacification (PCO) between the 1-piece and 3-piece haptic designs of the foldable hydrophobic acrylic AcrySof intraocular lens (IOL) over a 5-year period.\n Randomized, prospective, patient- and examiner-masked clinical trial with intraindividual comparison.\n Fifty-two patients with bilateral age-related cataract (104 eyes).\n Each study patient had cataract surgery in both eyes and received a 1-piece AcrySof IOL in 1 eye and a 3-piece AcrySof IOL in the other eye. Follow-up examinations were performed at 1 week, 1 month, 6 months, and 1, 2, and 5 years. Digital retroillumination images were obtained of each eye. The amount of posterior capsule opacification (score range, 0-10) was assessed subjectively at the slit lamp and objectively using automated image analysis software 1, 2, and 5 years after surgery.\n Posterior capsule opacification score (scale, 0-10).\n There was no significant difference between the 1-piece and 3-piece AcrySof IOL in best-corrected visual acuity, overlap of rhexis and IOL, capsular folds, anterior capsule opacification, and posterior capsule opacification (1-piece AcrySof PCO score, 1.7+/-1.7; 3-piece AcrySof PCO score, 1.3+/-1.4; P = 0.30).\n Modification of the IOL haptic design of the sharp optic edged AcrySof IOL from a 3-piece to a 1-piece haptic design caused no significant change in PCO intensity and neodymium:yttrium-aluminium-garnet laser treatment rate 5 years after surgery.",
"To compare postoperative performance and stability of 6.0-mm optic single- and 3-piece acrylic foldable intraocular lenses (IOLs).\n Prospective, randomized, self-controlled trial.\n Eighty eyes of 40 patients with bilateral senile cataracts.\n Phacoemulsification and IOL implantation were performed. One eye of a patient was randomly assigned to the SA60AT single-piece IOL, and the contralateral eye was allocated to the MA60AC 3-piece IOL.\n Best-corrected visual acuity (BCVA), spherical equivalent, aqueous flare intensity, anterior chamber depth, amount of IOL decentration and tilt, area of anterior capsule opening, and degree of posterior capsule opacification (PCO) were measured 2 days, 1 week, and 1, 3, 6, and 12 months after surgery. Specular microscopy was performed at 12 months postoperatively.\n In the SA60AT group, the anterior chamber depth did not show significant changes after surgery (P>0.05; paired t test), and the refraction remained highly stable throughout the 1-year study period. The MA60AC group showed significant shallowing of the anterior chamber (P<0.05) and a myopic shift (P<0.05) up to 1 month after surgery. There were no significant differences between the 2 groups (P>0.05) in BCVA, aqueous flare intensity, the amount of IOL decentration, IOL tilt, area of anterior capsule opening, and degree of PCO throughout the 12-month follow-up period.\n Both the SA60AT single-piece and MA60AC 3-piece lenses showed a minimum amount of decentration, tilt, anterior capsule contraction, and PCO. Although the MA60AC showed significant forward shift and myopic refractive changes after surgery, the SA60AT displayed little axial movement associated with highly stable refraction after surgery. This feature of the SA60AT should facilitate earlier spectacle prescription and quicker visual/social rehabilitation of patients after cataract surgery.",
"To evaluate the prevalence and severity of posterior capsule opacification (PCO) in pediatric eyes with a foldable acrylic AcrySof (Alcon) intraocular lens (IOL) and age-related surgical methods.\n Department of Ophthalmology, University of Vienna, Medical School, Vienna, Austria.\n This prospective randomized study comprised 50 eyes of 34 children aged between 2 and 16 years. Eyes of children between 2 and 5.9 years were consecutively randomized to Group 1a (primary posterior capsulotomy and anterior vitrectomy) or Group 1b (optic capture in addition). Eyes of children between 6 and 16 years were consecutively randomized to Group 2a (primary posterior capsulotomy without anterior vitrectomy), Group 2b (optic capture in addition), or Group 2c (in-the-bag IOL implantation without opening the posterior capsule). Main outcome parameters were the incidence and severity of PCO formation, early postoperative complications, pigmented cell deposits on the IOL surface, and cataract morphology.\n The visual axis was clear at the last follow-up in all eyes in Groups 1a, 1b, 2a, and 2b except in 1 eye in Group 1a. Sixty-percent of eyes in Group 2c had PCO. The incidence of early postoperative complications was significantly higher in eyes that developed PCO than in those that maintained a clear visual axis. There was no evidence that cataract morphology influenced PCO rates.\n The AcrySof IOL was well tolerated in pediatric eyes. Optic capture was not necessary to ensure a clear visual axis. Primary posterior capsulotomy should be performed in preschool and uncooperative children and in eyes expected to have relatively high postoperative inflammation. Implanting the AcrySof in the bag and leaving the posterior capsule intact is acceptable for school children and juveniles with isolated developmental cataract.",
"To measure posterior capsule opacification (PCO) and neodymium:YAG (Nd:YAG) capsulotomy rates between the AcrySof MA30 intraocular lens (IOL) (Alcon) and the 1CU IOL (HumanOptics) in a fellow-eye comparison.\n Ophthalmology Department, St. Thomas' Hospital, London, United Kingdom.\n Thirty patients who had bilateral cataract surgery with a 1CU IOL prospectively randomly allocated to 1 eye and an AcrySof MA30 monofocal IOL to the other eye were examined. Best corrected distance visual acuity was recorded using the Early Treatment Diabetic Retinopathy Study logMAR chart. Digital retroillumination images of the posterior capsule were taken with the pupil dilated and analyzed with POCO software.\n Eyes with the 1CU IOL had significantly higher PCO rates than eyes with the MA30 IOL at all time points. By 2 years after surgery, 50% of eyes with a 1CU IOL had required Nd:YAG capsulotomy compared with no eyes with an MA30 IOL. There was no significant difference in visual acuity at any time point when post Nd:YAG capsulotomy was taken in to account.\n The 1CU IOL has 4 broad optic-haptic junctions where the square-edged barrier is breached; this appeared to allow passage of lens epithelial cells, leading to an increase in PCO. However, the increased PCO cannot be attributed to this alone as the 1CU is hydrophilic, a factor known to be associated with higher PCO rates.",
"Laboratory studies in experimental animals suggest that use of nonsteroidal anti-inflammatory drugs decreases the incidence of posterior capsular opacification (PCO) following cataract surgery. Recently the incidence of PCO following cataract surgery and intraocular lens implantation was reported to be no different following postoperative treatment with diclofenac sodium 0.1% (Voltaren, Ciba Vision) or with dexamethasone 0.1% (Maxidex, Alcon). We studied the incidence of PCO in patients following treatment with diclofenac 0.1% and ketorolac tromethamine 0.5% (Acular, Allergan) ophthalmic solutions 3 years after cataract surgery and implantation of a foldable silicone intraocular lens.\n A total of 120 patients underwent phacoemulsification and implantation of a foldable silicone intracular lens. Patients were treated with either diclofenac 0.1% ophthalmic solution or 0.5% ketorolac ophthalmic solution 4 times daily for 30 days in a double-masked, randomized fashion during the postoperative period. Patients were examined 3 years following surgery by a masked observer who determined which patients received YAG capsulotomies and graded any existing PCO.\n Each treatment group had 12% YAG capsulotomies 3 years following surgery. Although PCO was present more often with diclofenac treatment (25/62) than with ketorolac treatment (16/58), this difference is not statistically significant (P = .142). Patients tolerated both treatments well without a difference in toxic effects or tolerability.\n This study did not demonstrate a difference in the ability of diclofenac or ketorolac ophthalmic solutions to prevent PCO following cataract extraction and implantation of an intraocular lens. Both treatment regimens were equally well tolerated.",
"The most common surgically related cause of reduced vision after extracapsular cataract extraction is posterior capsule opacification (PCO), which occurs in up to 50% of eyes following cataract extraction. This study examined whether small capsulorhexes of 4.5 to 5.0 mm, which lie completely on the 5.5 mm intraocular lens (IOL), and large capsulorhexes of 6.0 to 7.0 mm, which lie completely off the lens optic, are effective in preventing PCO development.\n In this prospective study, 496 eyes of 367 patients underwent standardized phacoemulsification with capsulorhexis and capsular bag foldable acrylic IOL implantation. The patients were randomly assigned to receive either a small capsulorhexis of 4.5 to 5 mm to lie completely on the IOL optic or a large capsulorhexis of 6 to 7 mm to lie completely off the lens optic. Retroillumination photographs were taken at 6 months and then yearly.\n Throughout the follow-up, there was less PCO in the small capsulorhexis group than in the large capsulorhexis group. CONCLUSIONS.:Small capsulorhexes were associated with less wrinkling of the posterior capsule and less PCO than were large capsulorhexes. PCO after IOL implantation has a multifactored pathogenesis. Small (4.5 to 5.0 mm) capsulorhexis and capsular bag implantation of 5.5 mm acrylic IOL are likely to reduce the PCO incidence when compared with the 6.0 to 7.0 mm capsulorhexis. The significance of the IOL optic diameter in association with the capsulorhexis size should also be documented by further studies.",
"To determine whether a capsular bending ring (CBR) with a rectangular cross-section and sharp edges moves the barrier to the very equator and avoids contact between the capsulorhexis and optic to prevent posterior capsule opacification (PCO) and anterior capsule fibrosis.\n Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.\n A 0.7 mm high, open poly(methyl methacrylate) CBR was implanted in 60 eyes (patients) in a prospective randomized intraindividual trial. The impact of additional CBR implantation on PCO and anterior capsule fibrosis was compared to that of intraocular lens (IOL) implantation alone using objective scoring.\n No CBR-related surgical complications occurred. The objective PCO score and area were statistically significantly reduced in the CBR group. In patients with complete follow-up, the mean PCO score (scale 1 to 10) at 1, 2, and 3 years was 0.8, 1.7, and 2.1, respectively, in the CBR group and 2.6, 3.9, and 4.6, respectively, in the no-CBR group. The number of quadrants affected by PCO was 0.9, 1.5, and 1.8 versus 3.2, 3.8, and 3.8. Barrier failures with the CBR were caused by the inherent slight edge blunting and occasional eyelet gaping. Laser capsulotomies were performed in the no-CBR group only. Capsule stress folds and fibrotic anterior capsule opacification were also greatly reduced. The best corrected visual acuity was better in the CBR group.\n Capsular bending ring implantation was an effective and safe adjunct to in-the-bag IOL fixation. With improvements in technology and design securing exquisitely sharp edges and circumferential capsular bending independent of the capsular bag diameter, this concept has the potential to prevent PCO and anterior capsule fibrosis.",
"To evaluate the effect of dexamethasone, diclofenac, and a placebo given for 3 weeks after phacoemulsification and intraocular lens (IOL) implantation on the formation of posterior capsule opacification (PCO).\n St. Erik's Eye Hospital, Stockholm, Sweden.\n In a 2-year prospective randomized double-blind study, a laser flare meter was used to measure aqueous flare intensity preoperatively and 3 days, 2 weeks, and 2 years after phacoemulsification and IOL implantation. Posterior capsule opacification was evaluated 2 years postoperatively using retroillumination images taken with a Scheimpflug camera. The Evaluation of Posterior Capsule Opacification system was used to score the areas of PCO density.\n The median rate of PCO 2 years after phacoemulsification was 0.72 (range 0.32 to 1.57) in the dexamethasone group, 0.78 (range 0.19 to 2.14) in the diclofenac group, and 0.70 (range 0.35 to 1.70) in the placebo group. The differences were not statistically significant (P>.05; Kruskal-Wallis analysis of variance, multiple comparisons). The rate of neodymium:YAG laser posterior capsulotomy during the 2 years after surgery was not statistically different between groups (P>.05, chi-square test). There was no correlation (Spearman rank coefficient) between laser flare measurements and PCO formation in any group during the study (P>.05).\n Topical instillation of diclofenac, dexamethasone, or a placebo in the immediate period after phacoemulsification and IOL implantation did not seem to influence the formation of PCO 2 years after cataract surgery.",
"To compare the formation and rates of posterior capsule opacification (PCO) in eyes with poly(methyl methacrylate) (PMMA) versus silicone intraocular lenses (IOLs) using an in vivo objective method.\n Taipei Municipal Yang-Ming Hospital, Taipei, Taiwan, Republic of China.\n This prospective study comprised 40 eyes with senile cataract receiving phacoemulsification with capsular implantation of an IOL from March to April 1997. The uneventful surgeries were performed using the stop and chop method by the same surgeon. Twenty eyes received a PMMA IOL (Pharmacia 812A) and 20, a silicone IOL (AMO SI-30NB). One year later, digital retroillumination images taken with the EAS-1000 anterior segment analysis system (Nidek) were used to analyze posterior capsule transparency over the central 3.0 and 5.0 mm optic zones and evaluate the degree of PCO over the central and peripheral zones.\n Over the central 5.0 mm optic zone, mean transparency of the capsule was 87.71% +/- 11.35% (SD) in the silicone group and 79.22% +/- 21.10% in the PMMA group (P = .17). Over the central 3.0 mm optic zone, the means were 97.17% +/- 5.96% and 86.32% +/- 19.60%, respectively (P = .048). Mean opacity in the central zone was 75.18 +/- 13.22 digital opacity units (OUs) in the silicone group and 80.24 +/- 7.93 OUs in the PMMA group (P = .18). The means in the peripheral zone were 88.49 +/- 18.47 OUs and 90.35 +/- 9.98 OUs, respectively (P = .71).\n The posterior capsule in the silicone IOL group was more transparent than in the PMMA IOL group over the central 3.0 mm optic zone after 1 year follow-up.",
"To evaluate the intraocular safety of an immunoconjugate (MDX-RA) developed to prevent posterior capsule opacification (PCO) in human eyes.\n St. Thomas's Hospital Eye Department, London, United Kingdom.\n Twenty-six patients had phacoemulsification and implantation of an intraocular lens (IOL). All were randomly allocated at the end of surgery to receive a 0.1 mL placebo or 0.1 mL of the immunotoxin MDX-RA intracamerally. Two doses of the drug were tested: 8 patients with a low dose (50 units), 9 patients with a high dose (100 units), and 9 with placebo. Follow-up at days 1, 14, 30, 60, 90, and 180 consisted of visual acuity measured by the Early Treatment of Diabetic Retinopathy Study test, contrast sensitivity, aqueous flare, specular microscopy of the IOL's anterior surface, and corneal endothelial counts. The percentage area of PCO was measured from retroillumination images of the posterior capsule.\n There was no decrease in corneal endothelial cell count in toxin-treated patients. Early postoperative flare, anterior chamber cell count, and corneal pachymetry were higher in toxin-treated patients. The median percentage area of PCO at 1 year was 32.0 in the placebo group, 3.8 in the low-dose group, and 7.4 in the high-dose group (P = .06).\n This prospective, randomized, placebo-controlled trial confirmed that MDX-RA is safe for intraocular use and is of potential value for further clinical trials of the prevention of PCO.",
"Intraocular lens (IOL) design, optical configuration, and placement have potential effects on postoperative outcome. Laboratory studies have suggested that one-piece, biconvex designs may reduce or delay posterior capsular opacification and that in-the-bag fixation of the posterior chamber IOL may reduce inflammation. To document the clinical significance of IOL design and placement, we conducted a randomized, prospective, clinical trial. Six hundred uncomplicated capsulorhexis and phacoemulsification patients were randomized in a three-factor design to receive an IOL that was one-piece or three-piece, had a biconvex, plano-convex, or laser ridge optic, and was bag-or sulcus-fixated. Treatment differences were related to lens placement. Patients with bag-fixated IOLs had less posterior capsular opacification, fewer YAG laser capsulotomies, a higher percentage of centered lenses, less inflammation, and fewer late posterior capsular striae than those with sulcus-fixated IOLs. In the latter group, patients with three-piece IOLs had fewer posterior capsular striae at three months postoperatively. All six occurrences of haptic loop distortion were in patients with three-piece IOLs. Patients with the one-piece design had less late inflammation than those with the three-piece design. Fewer YAG capsulotomies were necessary at one year in patients with the biconvex design than in those with the plano-convex or laser ridge configurations. Operative complications, endothelial cell loss, and postoperative complications were not IOL-related.",
"To investigate the incidence of posterior capsule opacification (PCO) in eyes treated with diclofenac sodium (DFNa) and betamethasone phosphate (BMS) ophthalmic solutions.\n A total of 200 eyes with silicone intraocular lens implantation were treated with topical agents for 3 months postoperatively. Twenty-six cases of the DFNa group and 34 of the BMS group met the criteria, and the severity of PCO was evaluated after 3 years.\n The results of axial densitometry by Scheimpflug photography were 27.8 computer-compatible tapes (CCT) in the DFNa-treated group and 32.6 CCT in the BMS-treated group (p = 0.1539). Posterior capsulotomy was performed in 11.5% of the DFNa group and 17.6% of the BMS group (p = 0.8375). The photographic grading of PCO showed no difference.\n The incidence of PCO in eyes treated with DFNa appears to be equal to that after BMS treatment.\n Copyright 2003 S. Karger AG, Basel",
"To evaluate whether heparin eyedrops prevent or reduce posterior capsule opacification (PCO) after extracapsular cataract extraction (ECCE) with intraocular lens (IOL) implantation.\n Institute of Ophthalmology, University G. d'Annunzio, Chieti, Italy.\n This 4 year, prospective, case-controlled study evaluated 200 patients who had ECCE and implantation of the same type of posterior chamber IOL. Patients were randomly assigned to receive topical heparin eyedrops postoperatively (heparin group, n = 100) or not to receive the eyedrops (control group, n = 100). Postoperative cell response, cellular precipitates on the IOL, and presence of PCO were evaluated.\n There were no significant differences between groups in postoperative inflammation. The incidence of cellular precipitates was significantly lower in the heparin group than in the control group (P < .001). A neodymium:YAG (Nd:YAG) posterior capsulotomy was done in 7 patients in the heparin group and 14 in the control group (P = .15). During the first 24 months after surgery, the heparin group had a significantly lower incidence of Nd:YAG capsulotomy (P < .05) and fibrotic PCO (P = .02).\n Topical heparin eyedrops were effective in reducing fibrotic PCO in the long term, indicating their usefulness in the postoperative management of ECCE.",
"The authors conducted a 3-year randomized trial to compare silicone intraocular lenses (IOLs) with polymethylmethacrylate (PMMA) IOLs, to determine any differences in laser capsulotomy rates, capsular opacification light scatter, and subjective scoring.\n A total of 119 patients were enrolled, 84 of whom were examined at 3 years. The authors designed a prospective, masked, and randomized trial to compare the objective (lens opacity meter), subjective (slit-lamp scoring), and clinical parameters of the posterior capsular opacification (PCO) of these patients.\n The silicone group had less PCO than the PMMA group, according to objective (8.6% vs. 10.4%; P = .02, Student's t test) and subjective scoring (0.88 vs. 1.79; P = .0001, Student's t test). The laser capsulotomy rate was 24% for the silicone group and 33% for the PMMA group; however, this difference was not statistically significant.\n The silicone IOL was associated with less PCO than the PMMA IOL.",
"To evaluate the efficacy of posterior continuous curvilinear capsulorhexis (PCCC) with optic capture of the posterior chamber intraocular lens (PC IOL) in the absence of vitrectomy in preventing secondary opacification of the visual axis following pediatric cataract surgery.\n Thirty-four eyes of 28 children with congenital or developmental cataract, aged 1.5 to 12 years (mean, 6.39 years), were included in this prospective, randomized study. Anterior continuous curvilinear capsulorhexis (ACCC) with PCCC without optic capture of the PC IOL was performed in group A (18 eyes) and ACCC with PCCC with optic capture of the PC IOL was performed in group B (16 eyes). None of the eyes underwent anterior vitrectomy. Secondary opacification of the visual axis, visual acuity, and possible complications were observed and analyzed.\n The follow-up period ranged from 8 to 28 months (mean, 17.5 months). All 16 eyes (100%) in group B had a clear visual axis at the end of follow-up. Eight eyes (44.4%) in group A had significant opacification of the visual axis. The difference between the two groups was statistically significant (P = .0011). No eye in group B required secondary intervention, whereas all 8 eyes in group A with significant secondary opacification required secondary intervention. There was no statistically significant difference in other complications such as anterior chamber reaction, fibrin formation, lenticular precipitates, and posterior synechiae. The final best-corrected visual acuity at the end of follow-up was comparable in the two groups (P > .05).\n PCCC with optic capture of the PC IOL prevents secondary opacification of the visual axis even in the absence of vitrectomy.",
"To present a new method to quantify posterior capsular opacity with an anterior eye segment image analyzer (EAS 1000, NIDEK).\n This study was comprised of patients who underwent phacoemulsification intraocular lens (IOL) implantation. Three types of IOLS, acrylic, silicone, and polymethylmethacrylate (PMMA) were allocated to 30 eyes and clinically evaluated. Patients were observed for 3 years postoperatively using an anterior eye segment image analyzer (EAS1000). Opacity was determined by calculating the area of opacity from a retroillumination image. In the retroillumination mode of analysis, the measurement was limited to a 4-mm-diameter region of the pupillary zone to eliminate the influence of anterior capsular opacity. For color map analysis, the threshold level was expressed as the color tone of 0-255 CCT (computer compatible tape). The glare disability was measured to evaluate the three types of IOLs.\n The color map analysis revealed a time-related increase in the opacity level of patients receiving the PMMA IOL implant. Three years after surgery, the levels were significantly higher in the PMMA group (P < 0.01) compared to the acryl and silicone groups: acryl (17.5 +/- 3.8), silicone (18.0 +/- 6.2%), and PMMA 36.5 +/- 32.9%.\n Quantitative evaluation using an anterior eye segment image analyzer is effective for observing the degree of posterior capsule opacification. The color map analysis using an anterior eye segment image correlated with the visual function revealed that the time-related increase in the opacity level was significant during the third year in patients receiving PMMA IOL implantation.",
"To evaluate the long-term effect of anterior capsule polishing on anterior capsule opacification (ACO) and peripheral fibrotic posterior capsule opacification (PCO).\n Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.\n This randomized double-blind study comprised 104 eyes of 52 patients with bilateral age-related cataract. All patients received round-edged intraocular lenses (IOLs); 26 received an SI-40 IOL (Advanced Medical Optics Inc.) in both eyes, and 26 received a Silens6 IOL (Domilens) in both eyes. Both IOLs consist of different silicone material and have different haptic angulation. The SI-40 IOL has 13.0 mm open-loop poly(methyl methacrylate) (PMMA) haptics angulated by 10 degrees. The Silens6 IOL has 12.5 mm open-loop PMMA haptics with no angulation. In 1 eye, the anterior capsule was extensively polished. The anterior capsule was left unpolished in the contralateral eye, which acted as a control. Digital slitlamp photographs of the ACO and fibrotic PCO were taken with a standardized technique for 3 years postoperatively. The intensity of ACO was measured objectively (score 0% to 100%) using Adobe Photoshop software. Fibrotic PCO was graded subjectively (score 0 to 4).\n The mean ACO was 17% in the polished eyes and 26% in the control eyes (P = .0001). The mean fibrotic PCO score was 0.5 and 1.0, respectively (P = .0007). The mean ACO was 15% in the polished SI-40 eyes and 26% in the control SI-40 eyes (P = .01). It was 19% in the polished Silens6 eyes and 26% in the control Silens6 eyes (P = .003). The mean fibrotic PCO score was 0.4 in the polished SI-40 eyes and 1.1 in the control SI-40 eyes (P = .0006). It was 0.6 in the polished Silens6 eyes and 0.9 in the control Silens6 eyes (P = .08).\n Three years after surgery, eyes in which the anterior capsule was extensively polished had less ACO and fibrotic PCO with both round-edged silicone IOLs. In eyes with Silens6 IOLs, however, the reduction in fibrotic PCO was not significant.",
"To quantitatively compare the extent of posterior capsule opacification (PCO) after polymethylmethacrylate (PMMA), silicone, and soft acrylic intraocular lens implantation.\n A total of 240 eyes from 240 patients undergoing implant surgery were randomized into 3 groups based on the type of lens implanted: PMMA, silicone, and soft acrylic. The density value of PCO in 185 eyes was quantitated approximately 2 years after surgery by a new measurement method using the Scheimpflug videophotography system.\n Twenty-one eyes (30.4%) in the PMMA group, 4 (5.7%) in the silicone group, and 2 (2.7%) in the acrylic group had already undergone Nd:YAG laser posterior capsulotomy. The mean +/- SD PCO values were 26.3 +/- 12.2 computer-compatible tape steps (CCT) in the PMMA group, 12.0 +/- 8.3 CCT in the silicone group, and 16.0 +/- 10.3 CCT in the acrylic group. The PCO value in the PMMA group was significantly greater than that in the silicone or acrylic group (P < .001). The visual acuity loss in the PMMA group was also greater than that in the silicone or acrylic group (P < .001).\n Based on the PCO value and capsulotomy rate, the PCO was more extensive with the PMMA lens than with either the silicone or soft acrylic lens, which led to visual acuity loss.",
"We investigated long-term safety and efficacy of sealed capsule irrigation (SCI) during cataract surgery to prevent posterior capsule opacification (PCO).\n One eye of each of 17 patients (mean age: 70.1+/-9.7 years) who presented with bilateral cataracts was randomly chosen for SCI treatment. After phacoemulsification, the capsular bag was vacuum sealed with the PerfectCapsule device (Milvella) followed by SCI using distilled water for two minutes. No vacuum loss occurred during irrigation. Each patient's fellow eye served as a control. One hydrophilic acrylic intraocular lens model was implanted in all eyes. Five patients had to be excluded due to deep anterior chamber, small pupil or unilateral surgery. Follow-up examinations took place one day and one, three, six, 12 and 24 months after surgery. We evaluated safety parameters, anterior capsule (AC) overlapping and PCO.\n Postoperatively, mean best corrected visual acuity, pachymetry, endothelial cell count, intraocular pressure, AC overlapping and PCO showed no statistically significant difference between SCI and the control group (p>0.05, Wilcoxon test).\n SCI is a safe procedure and enables the specific pharmacological targeting of lens epithelial cells inside the capsular bag. Using distilled water, however, it is not possible to reduce PCO development significantly. Thus, alternative substances should be evaluated.",
"To compare the postoperative performance of single and three piece acrylic foldable intraocular lenses (IOLs).\n 20 patients underwent bilateral cataract surgery with a single piece SA30AL IOL in one eye and a three piece MA30BA IOL in the other eye. The eyes were randomly assigned to either a single or three piece lens. The amount of IOL decentration and tilt, area of anterior capsule opening, and degree of posterior capsule opacification were measured using the Scheimpflug anterior segment analysis system (Nidek EAS-1000). Visual acuity and contrast sensitivity were examined. Measurements were performed by masked examiners before and 1 day, 1 week, 1, 3, 6, and 18 months after surgery.\n There were no significant differences between the two groups (p>0.05, paired t test) in the amount of IOL decentration, IOL tilt, area of anterior capsule opening, degree of posterior capsule opacification, best corrected visual acuity, and contrast sensitivity throughout the 18 month follow up period.\n The single and three piece acrylic foldable IOLs are equally stable in the eye after surgery.",
"In this randomized, prospective clinical study, a convex plane intraocular lens (IOL) with a laser ridge was compared with a convex plane IOL without a laser ridge. No difference was found in the reduction of capsular opacification 1 year after surgery. The 100 patients (40 males/60 females) with senescent cataracts were treated with ECCE by a single surgeon from November 1986 to March 1987. The operative technique consisted of capsulorhexis, irrigation-aspiration and in-the-bag-implantation. The first group of 50 patients (50 eyes) had an IOL without a laser ridge and the second group an IOL with a laser ridge. When considering after-cataracts in combination with minor visual deterioration we had secondary cataract rate of 15% in the IOL group with a laser ridge and of 16% in the IOL group without a laser ridge. When we considered only the cases in which visual acuity worsened and YAG laser capsulotomy was required, the secondary cataract rate was 1.5%.",
"To evaluate and to compare the preventive effect of different intraocular lenses from different material with a round or sharp optic edge design on posterior capsule opacification.\n Our clinical study included 165 patients. Mean follow-up was 12.4+/-0.9 months, mean patient age was 67.5+/-7.8 years. Patients in the group 1 (n=46) were implanted acrylic three-piece hydrophobic intraocular lenses, sharp optic edge (AcrySof, MA3OBA, Alcon), in the group 2 (n=38)--acrylic hydrophobic single piece intraocular lenses, sharp optic edge (AcrySof, SA3OAL, Alcon), in the group 3 (n=39)--silicone three-piece intraocular lenses, sharp optic edge (CeeOn 911A, Pharmacia), and in the group 4 (n=42)--polymethyl methacrylate single piece intraocular lenses, round optic edge (Crystal, 5T, Alcon). The posterior capsule opacification was evaluated for the entire optic and in the central 3-mm zone using EPCO 2000 Software.\n Posterior capsule opacification values of the entire optic were 0.002+/-0.001 in the AcrySof MA3OBA group, 0.007+/-0.002 in the AcrySof SA3OAL group, 0.002+/-0.001 in the CeeOn 911A group, 0.029+/-0.008 in the polymethyl methacrylate intraocular lens group 6 months after surgery. The values were 0.011+/-0.005, 0.025+/-0.006, 0.014+/-0.005 and 0.122+/-0.021, respectively, one year after surgery. The intraocular lenses types with sharp-edge design (acrylic and silicone) showed significantly lower posterior capsule opacification values than round-edge optic design polymethyl methacrylate lenses (p<0.05). Posterior capsule opacification values of the central 3-mm zone were 0.000+/-0.000 in the AcrySof MA3OBA group, 0.001+/-0.001 in the AcrySof SA3OAL group, 0.000+/-0.000 in the CeeOn 911A group, 0.002+/-0.001 in the polymethyl methacrylate intraocular lens group 6 months after surgery. The values were 0.0001+/-0.0001, 0.018+/-0.007, 0.004+/-0.002 and 0.028+/-0.009, respectively, one year after surgery. Posterior capsule opacification values differences between AcrySof MA3OBA and polymethyl methacrylate intraocular lenses' groups and between CeeOn 911A and polymethyl methacrylate intraocular lenses' groups one year after cataract surgery were established (p<0.05).\n The sharp-edge foldable intraocular lenses types (AcrySof MA3OBA, AcrySof SA3OAL, CeeOn 911A) showed statistically significant difference in posterior capsule opacification values in one-year follow-up time. The effect of these foldable lenses for prevention of posterior capsule opacification is mainly a result of rectangular, sharp-edged optic design, which creates a sharp capsular bend. A role of material of intraocular lenses (hydrophobic acrylate and silicone) in prevention of posterior capsule opacification during one-year follow-up was not established.",
"To compare the rates of lens epithelial cell (LEC) migration and posterior capsule opacification (PCO) 1 and 3 years after sutureless small incision phacoemulsification and in-the-bag implantation of 2 acrylic polymer intraocular lenses (IOLs)-the AcrySof and MemoryLens-in fellow eyes of patients.\n Eye Clinic, Beyoğlu Education and Research Hospital, Istanbul, Turkey.\n Fifty patients with no systemic or ocular problems that would interfere with postoperative visual acuity were included in this prospective study. Each patient had in-the-bag implantation of an AcrySof IOL in 1 eye and a MemoryLens in the fellow eye in a randomized fashion after uneventful phacoemulsification through a sutureless clear corneal incision.\n At 1 year (n = 32 patients), there was no significant difference between fellow eyes in postoperative best corrected visual acuity (BCVA) and contrast sensitivity. In the MemoryLens group, 10 eyes (31.3%) had PCO and 9 (28.1%), LEC migration. In the AcrySof group, no eye had PCO and 2 eyes (6.3%) had LEC migration (P <.001). At 3 years (n = 21 patients), 1 eye (4.7%) in the AcrySof group had PCO and 3 eyes (14.4%) had LEC migration without PCO. In the MemoryLens group, 1 eye (4.7%) had a clear posterior capsule, 11 eyes (52.4%) had LEC migration, and 9 eyes (42.9%) had PCO (P <.001). A neodymium:YAG capsulotomy was required in 4 eyes (19.0%) in the MemoryLens group but no eye in the AcrySof group. At 3 years, BCVA was lower in the MemoryLens group than in the AcrySof group (P <.05).\n The 3 year clinical data of fellow eyes indicate that the AcrySof IOL causes less PCO than the MemoryLens.",
"To evaluate intraindividual differences in posterior capsule opacification (PCO) and visual performance of AcrySof SN60AT (Alcon Laboratories) and AF-1 YA-60BB (Hoya Corp.) intraocular lenses (IOLs).\n Ophthalmology Department, St. Thomas' Hospital, London, United Kingdom.\n In this prospective single-surgeon standardized-surgical-procedure fellow-eye comparison, an AcrySof SN60AT or an AF-1 YA-60BB IOL was randomized to the first eye of 36 patients and fellow-eye surgery was performed within 4 to 6 weeks. Follow-up was at 1, 3, 6, 12, and 24 months. Best distance- corrected logMAR visual acuity was measured at 100% and 9% contrast. Contrast sensitivity was measured using the Functional Acuity Contrast Test (FACT) on the Optec 3500 instrument (Stereo Optical Company, Inc.). Color vision was assessed with the Farnsworth Munsell 100-hue test. After pupil dilation, digital retroillumination photographs were taken and the percentage area of PCO was calculated using POCO software.\n Posterior capsule opacification was significantly greater in the AF-1 YA-60BB group than in the AcrySof SN60AT group at all time points (P<.0001), with the difference greatest at 24 months. At 24 months, 100% contrast visual acuity was significantly better in the AcrySof SN60AT group than in the AF-1 YA-60BB group (P = .0313); 9% contrast visual acuity was significantly better in the AcrySof SN60AT group from 6 months onward. There was no significant difference between groups in color vision or contrast sensitivity. Electron microscopy showed the AcrySof SN60AT IOL has a much sharper posterior edge profile.\n The AcrySof SN60AT IOL had better PCO performance and thus visual performance than the AF-1 YA-60BB IOL. This is attributable to the differences in optic edge design.",
"Extracapsular cataract extraction (ECCE) with a posterior chamber intraocular lens (PC IOL) is the preferred method of cataract surgery in developed countries. However, intracapsular cataract extraction (ICCE) with an anterior chamber lens (AC IOL) may be appropriate in rural Africa. A randomised controlled trial was carried out to compare these surgical strategies.\n Participants over 50 years requiring bilateral cataract surgery were recruited from outreach clinics in rural north and east Uganda. One eye was randomly allocated to AC IOL or PC IOL, the other eye being allocated to the second strategy. The main outcome measure was WHO distance visual acuity (VA) category after a minimum of 1 year. Secondary outcomes were numbers and causes of complications and refractive corrections.\n Of the 110 participants recruited, 98 (89%) were assessed at least 1 year after the operation (median follow up 17.5 months). Nine eyes randomised to PC IOL were converted to AC IOL; one eye randomised to AC IOL inadvertently received PC IOL. There was no difference in VA between 95 pairs of eyes for which data for both eyes were available (uncorrected VA, p = 0.26; corrected VA, p = 0.59). 80 (82%, 95% CI 73 to 89) and 82 (84%, 95% CI 75 to 90) eyes randomised to AC IOL and PC IOL respectively had corrected VA of 6/18 or better. 16 (16%, 95% CI 10 to 25) and eight (8%, 95% CI 4 to 15) eyes respectively had secondary procedures or other complications.\n Where both strategies are available, ECCE with PC IOL should be first choice because of fewer complications. Where ECCE with PC IOL is not immediately feasible, ICCE with AC IOL is an acceptable interim technique.",
"To compare the inflammatory response after phacoemulsification and intraocular lens (IOL) implantation using postoperative treatment with dexamethasone, diclofenac, or placebo.\n A prospective, randomised, controlled double masked study including 180 patients enrolled for cataract surgery. The patients were 64-85 years old and had no eye disease other than cataract. After phacoemulsification and IOL implantation the patients were randomised to topical treatment with dexamethasone phosphate 0.1% (group I), diclofenac sodium 0.1% (group II), or placebo (saline 0.9%) (group III). The drops were administered four times daily during the first week and twice daily during the second, third, and fourth weeks. The inflammatory reaction in the anterior chamber was measured with laser flare photometry preoperatively and 1, 3, and 8 days, 2 and 4 weeks, 2 and 6 months, and 1, 2, and 4 years postoperatively. Inflammatory symptoms were registered. Biomicroscopy and visual acuity determinations were performed. The rate of Nd:YAG laser posterior capsulotomies after 2 and 4 years was determined.\n After 3 and 8 days (p <0.0001), 2 weeks (p <0.0001), and 1 month (p = 0.0013) median flare was highest in group III. There were no significant differences between group I and II. Inflammatory symptoms and striate keratopathy were more common in group III.\n Dexamethasone and diclofenac were equally effective in reducing postoperative inflammation after phacoemulsification and IOL implantation in eyes with no other disease than cataract. Both substances were more effective than placebo.",
"To evaluate the effect of intraocular lens (IOL) haptic compressibility on the posterior capsule after cataract surgery.\n Teaching hospital, London, United Kingdom.\n In this randomized prospective study, 60 patients had standardized phacoemulsification with in-the-bag placement of a poly(methyl methacrylate) (PMMA) (Storz P497UV) or hydrogel (Storz Hydroview H60M) IOL. Both IOLs had PMMA haptics of identical configuration and length. The IOL haptic compressibility was measured in air and then during incubation in saline at 37 degrees C over 1 month. Digital retroillumination imaging was performed 1, 7, 28, 90, 180, 360, and 720 days postoperatively. The presence and duration of postoperative capsule folds were recorded and correlated with the haptic compressibility measurements, lens epithelial cell (LEC) growth patterns on the posterior capsule at 6 months, and the extent of posterior capsule opacification.\n On the first postoperative day, 21 patients (88%) in the Hydroview group had posterior capsule folds that persisted in 12 patients (50%) for 2 years. Nineteen patients (68%) in the PMMA group had folds at day 1 (P =.01), with 1 patient (3%) still having folds at 1 month (P =.0002) and no patient having folds at 3 months. At 6 months, 11 patients (46%) in the Hydroview group and no patient in the PMMA group had LEC growth in the direction of the folds. The PMMA IOLs showed a greater decrease in haptic compressibility during incubation.\n Haptic compressibility should be an important consideration in IOL design. The results suggest that to avoid posterior capsule folds, the compressibility should be less than 2.5 mN.",
"To compare the visual outcome, neodymium:YAG (Nd:YAG) capsulotomy rates, and percentage of posterior capsular opacification (PCO) seen with polymethylmethacrylate (PMMA), silicone, and polyacrylic intraocular lens implants 3 years after surgery.\n Randomized, prospective trial.\n Ninety eyes of 81 patients were examined at a British teaching hospital.\n Ninety eyes were prospectively randomized to receive a PMMA, silicone, or polyacrylic (AcrySof, Alcon, Fort Worth, TX) implant. All lenses had 6-mm disc optics with PMMA haptics. A standardized surgical protocol was performed by a single surgeon using an extracapsular technique with capsulorhexis; any surgical complications were excluded and all patients had standardized postoperative medication and follow-up.\n Patients were seen at 6 months and 1, 2, and 3 years after surgery. At 3 years, logarithm of the minimum angle of resolution (LogMAR) visual acuity and Pelli-Robson contrast sensitivity were measured and YAG capsulotomy rates determined. Posterior capsular opacification was assessed objectively by digital retroillumination imaging using dedicated software and calculated as the percentage area of opacified capsule.\n At 3 years, the overall follow-up rate was 71%: 19 patients were available for examination with polyacrylic lens implants, 22 with silicone, and 23 with PMMA. There was a significant difference in percentage PCO at 3 years among the lens types (P = 0.0001). Polyacrylic lenses were associated with less PCO (10%) than silicone (40%) and PMMA lenses (56%). The YAG capsulotomy rate was 0% for polyacrylic, 14% for silicone, and 26% for PMMA (P = 0.05). The visual acuity and contrast sensitivity were not significantly different among the three groups if patients with age-related macular degeneration and those requiring YAG capsulotomies are excluded.\n Intraocular lenses made from polyacrylic are associated with a significantly reduced degree of PCO and lower YAG rates.",
"To evaluate the safety and efficacy of extracapsular cataract extraction with posterior chamber intraocular lens (ECCE/PC-IOL) compared with intracapsular cataract extraction with aphakic glasses (ICCE-AG).\n In a nonmasked randomized controlled clinical trial, 3,400 bilaterally vision-impaired patients aged 40 to 75 years with operable cataract were randomly assigned to receive either ICCE-AG or ECCE/PC-IOL at the Aravind Eye Hospital in India. The surgery was performed by one of four study surgeons. Patients were hospitalized for 5 postoperative days, with follow-up visits at 2, 6, and 12 months after discharge. Postsurgery evaluations were conducted by two independent study ophthalmologists.\n At any single postoperative follow-up time point, there were no statistically significant differences of clinical relevance between treatment groups for any complication of a serious nature except cystoid macular edema, which was more common with ICCE (4.2% vs 1.6%). In general, whether of a trivial, intermediate, or serious nature, complication rates were low at each evaluation time point. Cumulatively, the incidence of serious complications of all types throughout the 1-year study period was 14.5% for patients in the ICCE-AG group and 7.7% in the ECCE group (P < .001). Best-corrected visual acuity of 20/40 or better at 12 months was attained by 90.7% of ICCE-AG patients and 96.3% of ECCE/PC-IOL patients (P < .001).\n Although both operative procedures are safe and effective for cataract patients with bilateral impairment, ECCE/PC-IOL is superior to ICCE-AG in terms of both visual acuity restoration and safety.",
"Intraocular lens (IOL) haptic position in 35 eyes that had undergone cataract surgery was examined with ultrasound biomicroscopy (UBM).\n In a prospective randomized study the patients were operated by phacoemulsification using continuous curvilinear capsulorhexis (CCC) (group I) or by extracapsular cataract extraction (ECCE) using linear capsulotomy (group II). Ultrasound biomicroscopy was used to localize both haptics of the implanted intraocular lenses and to measure anterior chamber depth (ACD), iris thickness and anterior chamber angle. The inflammatory reaction in the anterior chamber was assessed with laser flare photometry. Slit lamp examination was performed.\n Both IOL haptics were found in the lens capsule in all 18 eyes in group I. In group II one of the haptics was located out of the capsule in 7 of 17 eyes (41%). The difference is statistically significant (p=0.01). Postoperatively mean ACD measured with the UBM was 4.06+/-0.30 mm in group I and 3.64+/-0.24 mm in group II (p=0.00025).\n The UBM examinations indicate that phacoemulsification with continuous curvilinear capsulorhexis is a more reliable technique than ECCE with linear capsulotomy to achieve implantation of the intraocular lens haptics in the capsular bag.",
"To evaluate safety and efficacy of Array SA40N multifocal intraocular lens (IOL) (AMO) implantation in cataract surgery.\n Helsinki University Eye Hospital, Helsinki, Finland.\n In this prospective randomized comparative trial, 80 patients scheduled for cataract surgery were selected based on preoperative counseling and randomized to have multifocal or monofocal IOL implantation. Fifty-three eyes of 35 patients received a multifocal IOL and 67 eyes of 40 patients, a monofocal IOL. The incidence of complications and visual outcome in the multifocal and monofocal IOL groups were compared. Quality of vision was measured by comparing the severity of visual symptoms (glare, halos, and cataract symptoms score), changes in functional impairment measured by a 7-item visual function test (VF-7), changes in global measures of vision (trouble and satisfaction with vision), and range of accommodation and contrast sensitivity.\n Intraoperative and postoperative complications and adverse events were few and required no further surgical intervention. Both distance and near visual acuities were significantly better in the multifocal group than in the monofocal group; the difference was most prominent in distance corrected near acuity (P<.001). Thirty-five eyes (67.3%) in the multifocal group and 10 eyes (14.9%) in the monofocal group achieved a distance corrected near acuity of J6 (20/40) or better; 30 eyes (56.6%) and 19 eyes (28.4%), respectively, achieved a best corrected distance acuity of 20/20 or better. Glare symptoms decreased postoperatively in both groups but were slightly more common in the multifocal group. In contrast, halos were significantly more common at 1 month in the multifocal group (P<.001). Contrast sensitivity values were slightly lower with multifocal IOLs at almost all spatial frequencies, but the difference was not significant. The change in the quality of life postoperatively, measured with the VF-7, was significant and identical in both groups.\n Pseudophakic eyes with multifocal IOLs had better distance and near acuity and range of accommodation than eyes with a monofocal IOL. Slightly lower contrast sensitivity and increased perception of halos by subjects with the multifocal IOL appear to be an acceptable compromise to enhanced near and distance vision."
] |
Due to the highly significant difference between round and sharp edged IOL optics, IOLs with sharp (posterior) optic edges should be preferred. There is no clear difference between optic materials. The choice of postoperative anti-inflammatory treatment does not seem to influence PCO development.
|
CD001814
|
[
"18237352",
"11730399",
"15110063",
"12694632",
"11129745",
"1315663",
"14679271",
"20207411",
"15066200",
"19775439",
"12928469",
"7539121",
"10404442",
"11298072",
"15599947",
"19107130",
"19091806",
"14671473",
"12038883",
"15161896",
"19707060",
"15113492",
"11677701",
"10404919",
"18807252",
"17456241",
"10480824",
"19152024",
"12096294",
"16330624",
"14528540",
"15514186",
"17509808"
] |
[
"Strategies for improving the quality of health care in maternal and child health in low- and middle-income countries: an overview of systematic reviews.",
"Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses.",
"Expanding developmental and behavioral services for newborns in primary care; Effects on parental well-being, practice, and satisfaction.",
"Randomised controlled trial of a theoretically grounded tailored intervention to diffuse evidence-based public health practice [ISRCTN23257060].",
"Effects of a multicomponent intervention on functional outcomes and process of care in hospitalized older patients: a randomized controlled trial of Acute Care for Elders (ACE) in a community hospital.",
"Impact of random assignment on study outcome: an empirical examination.",
"A practice-based intervention to enhance quality of care in the first 3 years of life: the Healthy Steps for Young Children Program.",
"Effect of a participatory intervention with women's groups on birth outcomes and maternal depression in Jharkhand and Orissa, India: a cluster-randomised controlled trial.",
"An outreach intervention to implement evidence based practice in residential care: a randomized controlled trial [ISRCTN67855475].",
"A randomized controlled trial evaluating the impact of knowledge translation and exchange strategies.",
"Association of funding and conclusions in randomized drug trials: a reflection of treatment effect or adverse events?",
"A randomized clinical trial of home intervention for children with failure to thrive.",
"A randomized, controlled trial of nurse home visiting to vulnerable families with newborns.",
"Outcomes of a randomized controlled trial of a clinical pharmacy intervention in 52 nursing homes.",
"Effects of a family intervention on the quality of life of women with recurrent breast cancer and their family caregivers.",
"Development and pilot evaluation of a complex intervention to improve experienced continuity of care in patients with cancer.",
"Conducting a randomized clinical trial of an psychological intervention for parents/caregivers of children with cancer shortly after diagnosis.",
"A three-center, randomized, controlled trial of individualized developmental care for very low birth weight preterm infants: medical, neurodevelopmental, parenting, and caregiving effects.",
"A randomized, controlled trial of a community-based support program for families of children with chronic illness: pediatric outcomes.",
"Empirical evidence for selective reporting of outcomes in randomized trials: comparison of protocols to published articles.",
"The tools of an evidence-based culture: implementing clinical-practice guidelines in an Israeli HMO.",
"Exploratory cluster randomised controlled trial of shared care development for long-term mental illness.",
"Randomised controlled trial of training health visitors to identify and help couples with relationship problems following a birth.",
"Chronic care clinics: a randomized controlled trial of a new model of primary care for frail older adults.",
"Combined intervention programme reduces inappropriate prescribing in elderly patients exposed to polypharmacy in primary care.",
"Practice development plans to improve the primary care management of acute asthma: randomised controlled trial.",
"Multifaceted shared care intervention for late life depression in residential care: randomised controlled trial.",
"An educational video to increase clinical trials enrollment among breast cancer patients.",
"Intervention to improve psychological functioning for newly diagnosed patients with cancer.",
"Systematic detection and multidisciplinary care of depression in older medical inpatients: a randomized trial.",
"The impact of tailored interventions on a community health center population.",
"Multicenter randomized controlled trial of an outreach nursing support program for recently discharged stroke patients.",
"The effects of a shared decision-making intervention in primary care of depression: a cluster-randomized controlled trial."
] |
[
"There are many systematic reviews of continuing education programmes and educational strategies for quality improvement in health care. Most of the reviewed studies are one-off evaluations rather than impact evaluations with long-term follow-up. There are few systematic reviews of organisational, financial and regulatory interventions, and few high-quality studies. These interventions are probably as or more important than educational strategies, although they are less well evaluated. Few studies have been undertaken in low- and middle-income countries (LMIC) or that address maternal and child health (MCH). Thus, the results of the available studies and reviews need to be interpreted cautiously when applied to LMIC. Interactive workshops, reminders and multifaceted interventions can improve professional practice, and they generally have moderate effects. Educational outreach visits consistently improve prescribing but have variable effects on other behaviours. Audit and feedback interventions have variable effects on professional practice, but most often these are small to moderate effects. Mass-media and patient-mediated interventions may change professional practice. Multifaceted interventions that combine several quality-improvement strategies are also effective but may not be more so than single interventions. While all of these strategies are applicable to MCH in LMIC, the applicability of the results to rural settings, in particular, may be limited. Use of these strategies could exacerbate inequalities, and this should be taken into consideration when planning implementation. Scaling up and sustainability may be difficult to achieve in LMIC contexts and need careful consideration. The use of financial interventions has not been well studied; financial incentives and disincentives may be difficult to use effectively and efficiently, although their impact on practice needs to be considered. Organisational interventions are likely to be important, given that there are often underlying organisational or system problems. Regulatory interventions have not been well evaluated, but may sometimes be both inexpensive and effective. There are no 'magic bullets' or simple solutions for ensuring the quality of health care services. Interventions should be selected or tailored to address the underlying reasons for a failure to deliver effective services. Decision-makers should select the most appropriate interventions for specific problems. This requires a governance structure that clearly assigns responsibility for quality-improvement activities, priority setting, selection and design of interventions, and evaluation.",
"To explore whether reported methodologic quality affects estimated intervention effects in randomized trials and contributes to discrepancies between the results of large randomized trials and small randomized trials in meta-analyses.\n Meta-analyses of randomized trials that included at least one large trial (>/=1000 participants) were included, regardless of the therapeutic area. Eligible meta-analyses were identified through electronic searches and bibliographies of relevant articles.\n Full-length randomized trials.\n Methodologic quality was assessed according to reported randomization, double blinding, and follow-up as separate components and by using the Jadad composite scale.\n Fourteen meta-analyses involving 190 randomized trials from eight therapeutic areas were included. Compared with large trials, intervention effects were exaggerated in small trials with inadequate allocation sequence generation (ratio of odds ratios, 0.46 [95% CI, 0.25 to 0.83]; P = 0.011), inadequate allocation concealment (ratio of odds ratios, 0.49 [CI, 0.27 to 0.86]; P = 0.014), and no double blinding (ratio of odds ratios, 0.52 [CI, 0.28 to 0.96]; P = 0.01). Large trials did not differ significantly from small trials with adequate generation of the allocation sequence, adequate allocation concealment, or adequate double blinding. No association was seen between reported follow-up and intervention effects. The Jadad scale provided no additional information because the scale and the quality components overlapped substantially.\n Inadequate generation of the allocation sequence, allocation concealment, and double blinding lead to exaggerated estimates of intervention benefit and may contribute to discrepancies between the results of large randomized trials and small randomized trials in meta-analyses.",
"Healthy Steps (HS) was designed to address, prospectively, behavioral and developmental support needs of young families in pediatric clinical care settings. PrePare (PP) initiates these services prenatally, whereas HS begins services in the postnatal period. Both interventions have universal and risk-directed components. Intervention effects in the first 3 months after birth are reported here.\n A quasi-experimental design was used to allocate 439 participants to intervention or usual care conditions. Within the intervention group, enrollees were randomly assigned to receive HS or PP+HS services. Early outcomes were assessed by telephone survey at 1 week and 3 months postpartum.\n Mothers in either intervention condition were less likely to report depressive symptoms and more likely to describe themselves as pleased in their role as parents. Intervention families were more likely to continue breastfeeding and more likely to read to their 3-month-old. Knowledge of infant development and recognition of appropriate discipline was greater among intervention recipients. Satisfaction with pediatric care was higher among intervention recipients and the rate of health plan disenrollment was 75% lower at 3 months among those enrolled in the prenatal intervention. No other outcome difference emerged between HS and PP+HS enrollees.\n Receipt of either intervention was associated with positive effects on health, safety, and developmentally appropriate parenting, as assessed in early infancy. There were positive effects on health plan disenrollment. No additional benefit could be ascribed to prenatal institution of services. A combination of universal and risk-based support for new parents is recommended, rather than the provision of risk-based services alone.",
"Previous studies have shown that Norwegian public health physicians do not systematically and explicitly use scientific evidence in their practice. They work in an environment that does not encourage the integration of this information in decision-making. In this study we investigate whether a theoretically grounded tailored intervention to diffuse evidence-based public health practice increases the physicians' use of research information.\n 148 self-selected public health physicians were randomised to an intervention group (n = 73) and a control group (n = 75). The intervention group received a multifaceted intervention while the control group received a letter declaring that they had access to library services. Baseline assessments before the intervention and post-testing immediately at the end of a 1.5-year intervention period were conducted. The intervention was theoretically based and consisted of a workshop in evidence-based public health, a newsletter, access to a specially designed information service, to relevant databases, and to an electronic discussion list. The main outcome measure was behaviour as measured by the use of research in different documents.\n The intervention did not demonstrate any evidence of effects on the objective behaviour outcomes. We found, however, a statistical significant difference between the two groups for both knowledge scores: Mean difference of 0.4 (95% CI: 0.2-0.6) in the score for knowledge about EBM-resources and mean difference of 0.2 (95% CI: 0.0-0.3) in the score for conceptual knowledge of importance for critical appraisal. There were no statistical significant differences in attitude-, self-efficacy-, decision-to-adopt- or job-satisfaction scales. There were no significant differences in Cochrane library searching after controlling for baseline values and characteristics.\n Though demonstrating effect on knowledge the study failed to provide support for the hypothesis that a theory-based multifaceted intervention targeted at identified barriers will change professional behaviour.",
"Older persons frequently experience a decline in function following an acute medical illness and hospitalization.\n To test the hypothesis that a multicomponent intervention, called Acute Care for Elders (ACE), will improve functional outcomes and the process of care in hospitalized older patients.\n Randomized controlled trial.\n Community teaching hospital.\n A total of 1,531 community-dwelling patients, aged 70 or older, admitted for an acute medical illness between November 1994 and May 1997.\n ACE includes a specially designed environment (with, for example, carpeting and uncluttered hallways); patient-centered care, including nursing care plans for prevention of disability and rehabilitation; planning for patient discharge to home; and review of medical care to prevent iatrogenic illness.\n The main outcome was change in the number of independent activities of daily living (ADL) from 2 weeks before admission (baseline) to discharge. Secondary outcomes included resource use, implementation of orders to promote function, and patient and provider satisfaction.\n Self-reported measures of function did not differ at discharge between the intervention and usual care groups by intention-to-treat analysis. The composite outcome of ADL decline from baseline or nursing home placement was less frequent in the intervention group at discharge (34% vs 40%; P = .027) and during the year following hospitalization (P = .022). There were no significant group differences in hospital length of stay and costs, home healthcare visits, or readmissions. Nursing care plans to promote independent function were more often implemented in the intervention group (79% vs 50%; P = .001), physical therapy consults were obtained more frequently (42% vs 36%; P = .027), and restraints were applied to fewer patients (2% vs 6%; P = .001). Satisfaction with care was higher for the intervention group than the usual care group among patients, caregivers, physicians, and nurses (P < .05).\n ACE in a community hospital improved the process of care and patient and provider satisfaction without increasing hospital length of stay or costs. A lower frequency of the composite outcome ADL decline or nursing home placement may indicate potentially beneficial effects on patient outcomes.",
"Sixty research investigations published in the biomedical literature were analyzed to examine the effect of design attributes on outcome. All 60 studies included a controlled trial involving a pretest, a therapeutic intervention, and a posttest across at least two groups. Thirty of the trials used random assignment of participants to treatment or control conditions and 30 trials employed some nonrandom method of subject assignment. Trial results were aggregated and evaluated by comparing effect sizes for the primary statistical test of the hypothesis. Data analysis revealed that the trial results, as measured by effect size, did not vary across therapeutic trials using random assignment versus those using nonrandom allocation of subjects. The impact of design attributes in the interpretation of multiple clinical trials addressing a similar research question is examined. The argument is made that various design attributes frequently associated with methodological quality should be considered as important moderator variables and their influence on trial outcome should not be assumed a priori but rather examined empirically.",
"There is growing concern regarding the quality of health care available in the United States for young children, and specific limitations have been noted in developmental and behavioral services provided for children in the first 3 years of life.\n To determine the impact of the Healthy Steps for Young Children Program on quality of early childhood health care and parenting practices.\n Prospective controlled clinical trial enrolling participants between September 1996 and November 1998 at 6 randomization and 9 quasi-experimental sites across the United States. Participants were 5565 children enrolled at birth and followed up through age 3 years.\n Incorporation of developmental specialists and enhanced developmental services into pediatric care in participants' first 3 years of life.\n Quality of care was operationalized across 4 domains: effectiveness (eg, families received > or =4 Healthy Steps-related services or discussed >6 anticipatory guidance topics), patient-centeredness (eg, families were satisfied with care provided), timeliness (eg, children received timely well-child visits and vaccinations), and efficiency (eg, families remained at the practice for > or =20 months). Parenting outcomes included response to child misbehavior (eg, use of severe discipline) and practices to promote child development and safety (eg, mothers at risk for depression discussed their sadness with someone at the practice).\n Of the 5565 enrolled families, 3737 (67.2%) responded to an interview at 30 to 33 months (usual care, 1716 families; Healthy Steps, 2021 families). Families who participated in the Healthy Steps Program had greater odds of receiving 4 or more Healthy Steps-related services (for randomization and quasi-experimental sites, respectively: odds ratio [OR], 16.90 [95% confidence interval [CI], 12.78 to 22.34] and OR, 23.05 [95% CI, 17.38 to 30.58]), of discussing more than 6 anticipatory guidance topics (OR, 8.56 [95% CI, 6.47 to 11.32] and OR, 12.31 [95% CI, 9.35 to 16.19]), of being highly satisfied with care provided (eg, someone in the practice went out of the way for them) (OR, 2.06 [95% CI, 1.64 to 2.58] and OR, 2.11 [95% CI, 1.72 to 2.59]), of receiving timely well-child visits and vaccinations (eg, age-appropriate 1-month visit) (OR, 1.98 [95% CI, 1.08 to 3.62] and OR, 2.11 [95% CI, 1.16 to 3.85]), and of remaining at the practice for 20 months or longer (OR, 2.02 [95% CI, 1.61 to 2.55] and OR, 1.75 [95% CI, 1.43 to 2.15]). They also had reduced odds of using severe discipline (eg, slapping in face or spanking with object) (OR, 0.82 [95% CI, 0.54 to 1.26] and OR, 0.67 [95% CI, 0.46 to 0.97]). Among mothers considered at risk for depression, those who participated in the Healthy Steps Program had greater odds of discussing their sadness with someone at the practice (OR, 0.95 [95% CI, 0.56 to 1.63] and OR, 2.82 [95% CI, 1.57 to 5.08]).\n Universal, practice-based interventions can enhance quality of care for families of young children and can improve selected parenting practices.",
"Community mobilisation through participatory women's groups might improve birth outcomes in poor rural communities. We therefore assessed this approach in a largely tribal and rural population in three districts in eastern India.\n From 36 clusters in Jharkhand and Orissa, with an estimated population of 228 186, we assigned 18 clusters to intervention or control using stratified randomisation. Women were eligible to participate if they were aged 15-49 years, residing in the project area, and had given birth during the study. In intervention clusters, a facilitator convened 13 groups every month to support participatory action and learning for women, and facilitated the development and implementation of strategies to address maternal and newborn health problems. The primary outcomes were reductions in neonatal mortality rate (NMR) and maternal depression scores. Analysis was by intention to treat. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN21817853.\n After baseline surveillance of 4692 births, we monitored outcomes for 19 030 births during 3 years (2005-08). NMRs per 1000 were 55.6, 37.1, and 36.3 during the first, second, and third years, respectively, in intervention clusters, and 53.4, 59.6, and 64.3, respectively, in control clusters. NMR was 32% lower in intervention clusters adjusted for clustering, stratification, and baseline differences (odds ratio 0.68, 95% CI 0.59-0.78) during the 3 years, and 45% lower in years 2 and 3 (0.55, 0.46-0.66). Although we did not note a significant effect on maternal depression overall, reduction in moderate depression was 57% in year 3 (0.43, 0.23-0.80).\n This intervention could be used with or as a potential alternative to health-worker-led interventions, and presents new opportunities for policy makers to improve maternal and newborn health outcomes in poor populations.\n Health Foundation, UK Department for International Development, Wellcome Trust, and the Big Lottery Fund (UK).\n Copyright 2010 Elsevier Ltd. All rights reserved.",
"The aim of this project was to assess whether outreach visits would improve the implementation of evidence based clinical practice in the area of falls reduction and stroke prevention in a residential care setting.\n Twenty facilities took part in a randomized controlled trial with a seven month follow-up period. Two outreach visits were delivered by a pharmacist. At the first a summary of the relevant evidence was provided and at the second detailed audit information was provided about fall rates, psychotropic drug prescribing and stroke risk reduction practices (BP monitoring, aspirin and warfarin use) for the facility relevant to the physician. The effect of the interventions was determined via pre- and post-intervention case note audit. Outcomes included change in percentage patients at risk of falling who fell in a three month period prior to follow-up and changes in use of psychotropic medications. Chi-square tests, independent samples t-test, and logistic regression were used in the analysis.\n Data were available from case notes at baseline (n = 897) and seven months follow-up (n = 902), 452 residential care staff were surveyed and 121 physicians were involved with 61 receiving outreach visits. Pre-and post-intervention data were available for 715 participants. There were no differences between the intervention and control groups for the three month fall rate. We were unable to detect statistically significant differences between groups for the psychotropic drug use of the patients before or after the intervention. The exception was significantly greater use of \"as required\" antipsychotics in the intervention group compared with the control group after the pharmacy intervention (RR = 4.95; 95%CI 1.69-14.50). There was no statistically significant difference between groups for the numbers of patients \"at risk of stroke\" on aspirin at follow-up.\n While the strategy was well received by the physicians involved, there was no change in prescribing patterns. Patient care in residential settings is complex and involves contributions from the patient's physician, family and residential care staff. The project highlights challenges of delivering evidence based care in a setting in which there is a paucity of well controlled trial evidence but where significant health outcomes can be attained.",
"Significant resources and time are invested in the production of research knowledge. The primary objective of this randomized controlled trial was to evaluate the effectiveness of three knowledge translation and exchange strategies in the incorporation of research evidence into public health policies and programs.\n This trial was conducted with a national sample of public health departments in Canada from 2004 to 2006. The three interventions, implemented over one year in 2005, included access to an online registry of research evidence; tailored messaging; and a knowledge broker. The primary outcome assessed the extent to which research evidence was used in a recent program decision, and the secondary outcome measured the change in the sum of evidence-informed healthy body weight promotion policies or programs being delivered at health departments. Mixed-effects models were used to test the hypotheses.\n One hundred and eight of 141 (77%) health departments participated in this study. No significant effect of the intervention was observed for primary outcome (p < 0.45). However, for public health policies and programs (HPPs), a significant effect of the intervention was observed only for tailored, targeted messages (p < 0.01). The treatment effect was moderated by organizational research culture (e.g., value placed on research evidence in decision making).\n The results of this study suggest that under certain conditions tailored, targeted messages are more effective than knowledge brokering and access to an online registry of research evidence. Greater emphasis on the identification of organizational factors is needed in order to implement strategies that best meet the needs of individual organizations.\n The trial registration number and title are as follows: ISRCTN35240937 -- Is a knowledge broker more effective than other strategies in promoting evidence-based physical activity and healthy body weight programming?",
"Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions.\n To explore whether the association between funding and conclusions in randomized drug trials reflects treatment effects or adverse events.\n Observational study of 370 randomized drug trials included in meta-analyses from Cochrane reviews selected from the Cochrane Library, May 2001. From a random sample of 167 Cochrane reviews, 25 contained eligible meta-analyses (assessed a binary outcome; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment). The primary binary outcome from each meta-analysis was considered the primary outcome for all trials included in each meta-analysis. The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect, adverse events, and additional confounding factors (methodological quality, control intervention, sample size, publication year, and place of publication).\n Conclusions in trials, classified into whether the experimental drug was recommended as the treatment of choice or not.\n The experimental drug was recommended as treatment of choice in 16% of trials funded by nonprofit organizations, 30% of trials not reporting funding, 35% of trials funded by both nonprofit and for-profit organizations, and 51% of trials funded by for-profit organizations (P<.001; chi2 test). Logistic regression analyses indicated that funding, treatment effect, and double blinding were the only significant predictors of conclusions. Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice (odds ratio, 5.3; 95% confidence interval, 2.0-14.4) compared with trials funded by nonprofit organizations. This association did not appear to reflect treatment effect or adverse events.\n Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results. Readers should carefully evaluate whether conclusions in randomized trials are supported by data.",
"To evaluate the efficacy of a home-based intervention on the growth and development of children with nonorganic failure to thrive (NOFTT).\n Randomized clinical trial.\n The NOFTT sample included 130 children (mean age, 12.7 months; SD, 6.4) recruited from urban pediatric primary care clinics serving low income families. All children were younger than 25 months with weight for age below the fifth percentile. Eligibility criteria included gestational age of at least 36 weeks, birth weight appropriate for gestational age, and no significant history of perinatal complications, congenital disorders, chronic illnesses, or developmental disabilities. Children were randomized into two groups: clinic plus home intervention (HI) (n = 64) or clinic only (n = 66). There were no group differences in children's age, gender, race, or growth parameters, or on any of the family background variables. Most children were raised by single, African-American mothers who received public assistance. Eighty-nine percent of the families (116 of 130) completed the 1-year evaluation.\n All children received services in a multidisciplinary growth and nutrition clinic. A community-based agency provided the home intervention. Families in the HI group were scheduled to receive weekly home visits for 1 year by lay home visitors, supervised by a community health nurse. The intervention provided maternal support and promoted parenting, child development, use of informal and formal resources, and parent advocacy.\n Growth was measured by standard procedures and converted to z scores for weight for height and height for age to assess wasting and stunting. Cognitive and motor development were measured with the Bayley Scales of Infant Development, and language development was measured by the Receptive/Expressive Emergent Language Scale. Both scales were administered at recruitment and at the 12-month follow-up. Parent-child interaction was measured by observing mothers and children during feeding at recruitment and at the 12-month follow-up, and the quality of the home was measured by the Home Observation Measure of the Environment 18 months after recruitment.\n Repeated-measures multivariate analyses of covariance were used to examine changes in children's growth and development and parent-child interaction. Analyses of covariance were used to examine the quality of the home. Independent variables were intervention status and age at recruitment (1.0 to 12.0 vs 12.1 to 24.9 months). Maternal education was a covariate in all analyses. When changes in developmental status and parent-child interaction were examined, weight for height and height for age at recruitment were included as covariates.\n Children's weight for age, weight for height, and height for age improved significantly during the 12-month study period, regardless of intervention status. Children in the HI group had better receptive language over time and more child-oriented home environments than children in the clinic-only group. The impact of intervention status on cognitive development varied as a function of children's ages at recruitment, with younger children showing beneficial effects of home intervention. There were no changes in motor development associated with intervention status. During the study period, children gained skills in interactive competence during feeding, and their parents became more controlling during feeding, but differences were not associated with intervention status.\n Findings support a cautious optimism regarding home intervention during the first year of life provided by trained lay home visitors. Early home intervention can promote a nurturant home environment effectively and can reduce the developmental delays often experienced by low income, urban infants with NOFTT: Subsequent investigations of home intervention should consider alternative options for toddlers with NOFTT:",
"This project aimed to evaluate the impact of a home visiting programme that targeted families where the child, for environmental reasons, was at great risk of poor health and developmental outcomes.\n Women in the immediate postpartum period were recruited to a randomized double-blind controlled trial on the basis of self-reported vulnerability factors and were randomly assigned to receive either a structured programme of nurse home visiting, supported by a social worker and paediatrician (n = 90), or assigned to a comparison group receiving standard community child health services (n = 91). Parenting stress and maternal depression were measured at enrollment and at 6 weeks. Preventive health behaviour, service satisfaction and home environment outcomes were tested at 6 weeks, as were child health outcomes.\n At six weeks, women receiving the home-based programme had significant reductions in postnatal depression screening scores as well as improvements in their experience of the parental role and improvement in the ability to maintain their own identity. Maternal-infant interactions were more likely to be positive, with significantly higher (better) scores in aspects of the home environment related to optimal development in children, particularly maternal-infant secure attachment. Intervention group mothers were significantly more satisfied with the community child health service.\n This form of intervention for families is effective in promoting secure maternal-infant attachment, preventing maternal mood disorder and is welcomed by the families receiving it. These findings may predict long-term benefits for the healthy development of children otherwise at risk of a range of poor health and development outcomes.",
"To evaluate whether a year long clinical pharmacy program involving development of professional relationships, nurse education on medication issues, and individualized medication reviews could change drug use, mortality and morbidity in nursing home residents.\n A cluster randomised controlled trial, where an intervention home was matched to three control homes, was used to examine the effect of the clinical pharmacy intervention on resident outcomes. The study involved 905 residents in 13 intervention nursing homes and 2325 residents in 39 control nursing homes in south-east Queensland and north-east New South Wales, Australia. The outcome measures were: continuous drug use data from government prescription subsidy claims, cross-sectional drug use data on prescribed and administered medications, deaths and morbidity indices (hospitalization rates, adverse events and disability indices).\n This intervention resulted in a reduction in drug use with no change in morbidity indices or survival. Differences in nursing home characteristics, as defined by cluster analysis with SUDAAN, negated intervention-related apparent significant improvements in survival. The use of benzodiazepines, nonsteroidal anti-inflammatory drugs, laxatives, histamine H2-receptor antagonists and antacids was significantly reduced in the intervention group, whereas the use of digoxin and diuretics remained similar to controls. Overall, drug use in the intervention group was reduced by 14.8% relative to the controls, equivalent to an annual prescription saving of A64 dollars per resident (approximately 25 pound sterling).\n This intervention improved nursing home resident outcomes related to changes in drug use and drug-related expenditure. The continuing divergence in both drug use and survival at the end of the study suggests that the difference would have been more significant in a larger and longer study, and even more so using additional instruments specific for measuring outcomes related to changes in drug use.",
"The purpose of this study was to determine if patients with advanced breast cancer and their family caregivers, who participated in a family based intervention, report better quality of life and other psychosocial outcomes than dyads who received standard care alone.\n Using a randomized clinical trial, 134 patients and their family caregivers were assigned to usual care (control) or to usual care plus the family intervention (experimental condition). Dyads were assessed at baseline, three- and six-months later. The intervention consisted of five sessions and addressed family involvement, optimistic attitude, coping effectiveness, uncertainty reduction, and symptom management.\n Patients in the family intervention reported significantly less hopelessness and less negative appraisal of illness than controls; their family caregivers reported significantly less negative appraisal of caregiving. Intervention effects were evident at three-months, but were not sustained at six-months. No difference was found in the quality of life of dyads in experimental or control conditions.\n Although the family intervention had positive effects initially, these effects were not sustained over time. Future studies need to consider program dose and duration of effect, outcome measures that are more sensitive to change, and realistic end-points for patients with advanced cancer.",
"High experienced continuity of care in patients with cancer is associated with lower needs for care, better quality of life and better psychological outcomes. We developed and evaluated an intervention to improve experienced continuity. The intervention, consisted of (1) a 17-item patient-completed continuity assessment; (2) feedback to clinical nurse specialists and action to address the needs identified. Multidisciplinary team meetings and oncology outpatient clinics were observed, and patients and staff were interviewed. After qualitative work and reliability testing, the intervention was evaluated in a feasibility trial. Sixty-one patients provided data for analysis. No statistically significant differences were found in patients' experienced continuity between the trial arms, but important trends were seen in measures of needs for care in favour of those receiving the intervention. Feeding back findings from the continuity assessment to clinicians reduced patients' needs for care. Our results indicate that an intervention to target patients' experiences of continuity can reduce their subsequent needs for care. However, overcoming barriers to organisational change and addressing some patients' hesitation to report their continuity difficulties must be considered when implementing such an intervention. A phase III trial targeting patients with inadequate experienced continuity of care is recommended.",
"To report acceptability, feasibility, and outcome data from a randomized clinical trial (RCT) of a brief intervention for caregivers of children newly diagnosed with cancer.\n Eighty-one families were randomly assigned following collection of baseline data to Intervention or Treatment as Usual (TAU). Recruitment and retention rates and progression through the protocol were tracked. Measures of state anxiety and posttraumatic stress symptoms served as outcomes.\n Difficulties enrolling participants included a high percentage of newly diagnosed families failing to meet inclusion criteria (40%) and an unexpectedly low participation rate (23%). However, movement through the protocol was generally completed in a timely manner and those completing the intervention provided positive feedback. Outcome data showed no significant differences between the arms of the RCT.\n There are many challenges inherent in conducting a RCT shortly after cancer diagnosis. Consideration of alternative research designs and optimal timing for interventions are essential next steps.",
"Medical, neurodevelopmental, and parenting effects of individualized developmental care were investigated in a three-center, randomized, controlled trial. A total of 92 preterm infants, weighing less than 1250 g and aged less than 28 weeks, participated. Outcome measures included medical, neurodevelopmental and family function. Quality of care was also assessed. Multivariate analysis of variance investigated group, site, and interaction effects; correlation analysis identified individual variable contributions to significant effects. The results consistently favored the experimental groups. The following contributed to the group effects: shorter duration of parenteral feeding, transition to full oral feeding, intensive care, and hospitalization; lower incidence of necrotizing enterocolitis; reduced discharge ages and hospital charges; improved weight, length, and head circumferences; enhanced autonomic, motor, state, attention, and self-regulatory functioning; reduced need for facilitation; and lowered family stress and enhanced appreciation of the infant. Quality of care was measurably improved. Very low birth weight infants and their parents, across diverse settings, may benefit from individualized developmental care.",
"Children with chronic illnesses have a heightened risk for mental health problems.\n To develop, implement, and evaluate child outcomes of a 15-month, community-based, family-support intervention designed to reduce risk for poor adjustment and mental health problems in children with 1 of 4 chronic illnesses (diabetes mellitus, sickle cell anemia, cystic fibrosis, or moderate to severe asthma) and their mothers.\n Randomized, controlled clinical trial design with multiple measures of mental health based on both child and parent reports taken 1 year apart.\n Community-based intervention linked to subspecialty and general pediatric clinics and practices in Baltimore, Md.\n One hundred thirty-six mothers and children aged 7 to 11 years with diabetes mellitus, sickle cell anemia, cystic fibrosis, or moderate to severe asthma.\n The program, provided by \"experienced mothers\" and child life specialists, included telephone contacts, face-to-face visits, and special family events.\n Outcomes were measured using the following instruments: the Personal Adjustment and Role Skills Scale III, the Children's Depression Inventory, the Revised Children's Manifest Anxiety Scale, and the Self-Perception Profile for Children.\n The experimental group's mean adjustment score increased over the intervention period while the control group's mean adjustment score decreased. Analysis of variance demonstrated that the intervention had a significant main effect on postintervention adjustment controlling for baseline scores (P =.01). Using a cutoff score indicating maladjustment, the percentage of experimental group children in the maladjustment range fell from 19% at baseline to 10% after the intervention; the percentage of control group children in the maladjustment range rose from 15% at baseline to 21% after the intervention. The effect of the intervention was more pronounced for children who had low physical self-esteem than for those who had moderate to high physical self-esteem at the beginning of the program.\n Our results demonstrate modest positive effects of a family support intervention in promoting the adjustment of children with selective chronic health conditions. Including child life specialists in a community-based intervention may be especially salient for children with chronic illnesses who have low physical self-esteem. The intervention had a similar outcome for all diagnostic groups, suggesting that it could be effective for children with any chronic illness and implemented in a variety of pediatric settings.",
"Selective reporting of outcomes within published studies based on the nature or direction of their results has been widely suspected, but direct evidence of such bias is currently limited to case reports.\n To study empirically the extent and nature of outcome reporting bias in a cohort of randomized trials.\n Cohort study using protocols and published reports of randomized trials approved by the Scientific-Ethical Committees for Copenhagen and Frederiksberg, Denmark, in 1994-1995. The number and characteristics of reported and unreported trial outcomes were recorded from protocols, journal articles, and a survey of trialists. An outcome was considered incompletely reported if insufficient data were presented in the published articles for meta-analysis. Odds ratios relating the completeness of outcome reporting to statistical significance were calculated for each trial and then pooled to provide an overall estimate of bias. Protocols and published articles were also compared to identify discrepancies in primary outcomes.\n Completeness of reporting of efficacy and harm outcomes and of statistically significant vs nonsignificant outcomes; consistency between primary outcomes defined in the most recent protocols and those defined in published articles.\n One hundred two trials with 122 published journal articles and 3736 outcomes were identified. Overall, 50% of efficacy and 65% of harm outcomes per trial were incompletely reported. Statistically significant outcomes had a higher odds of being fully reported compared with nonsignificant outcomes for both efficacy (pooled odds ratio, 2.4; 95% confidence interval [CI], 1.4-4.0) and harm (pooled odds ratio, 4.7; 95% CI, 1.8-12.0) data. In comparing published articles with protocols, 62% of trials had at least 1 primary outcome that was changed, introduced, or omitted. Eighty-six percent of survey responders (42/49) denied the existence of unreported outcomes despite clear evidence to the contrary.\n The reporting of trial outcomes is not only frequently incomplete but also biased and inconsistent with protocols. Published articles, as well as reviews that incorporate them, may therefore be unreliable and overestimate the benefits of an intervention. To ensure transparency, planned trials should be registered and protocols should be made publicly available prior to trial completion.",
"Although clinical-practice guidelines (CPGs) are implemented on the assumption that they will improve the quality, efficiency, and consistency of health care, they generally have limited effect in changing physicians' behavior. The purpose of this study was to design and implement an effective program for formulating, promulgating, and implementing CPGs to foster the development of an evidence-based culture in an Israeli HMO.\n The authors implemented a four-stage program of stepwise collaborative efforts with academic institutions composed of developing quantitative tools to evaluate prescribing patterns, updating CPGs, collecting MDs' input via focus groups and quantitative surveys, and conducting a randomized controlled trial of a two-stage, multipronged intervention. The test case for this study was the development, dissemination, and implementation of CPG for the treatment of acute uncomplicated cystitis in adult women. Interventions in the form of a lecture at a conference and a letter with personalized feedback were implemented, both individually and combined, to improve physicians' rates of prescribing the first-line drug, nitrofurantoin, and, in the absence of nitrofurantoin, adhering to the recommended duration of three days of treatment with ofloxacin.\n The tools and data-generating capabilities designed and constructed in Stage I of the project were integral components of all subsequent stages of the program. Personalized feedback alone was sufficient to improve the rate of adherence to the guidelines by 19.4% (95% CI = 16.7, 22.1).\n This study provides a template for introducing the component of experimentation essential for cultivating an evidence-based culture. This process, composed of collaborative efforts between academic institutions and a managed care organization, may be beneficial to other health care systems.",
"Primary care clinicians have a considerable amount of contact with patients suffering from long-term mental illness. The United Kingdom's National Health Service now requires general practices to contribute more systematically to care for this group of patients.\n To determine the effects of Mental Health Link, a facilitation-based quality improvement programme designed to improve communication between the teams and systems of care within general practice. Design of study: Exploratory cluster randomised controlled trial.\n Twenty-three urban general practices and associated community mental health teams.\n Practices were randomised to service development as usual or to the Mental Health Link programme. Questionnaires and an audit of notes assessed 335 patients' satisfaction, unmet need, mental health status, processes of mental and physical care, and general practitioners' satisfaction with services and beliefs about service development. Service use and intervention costs were also measured.\n There were no significant differences in patients' perception of their unmet need, satisfaction or general health. Intervention patients had fewer psychiatric relapses than control patients (mean = 0.39 versus 0.71, respectively, P = 0.02) but there were no differences in documented processes of care. Intervention practitioners were more satisfied and services improved significantly for intervention practices. There was an additional mean direct cost of pound 63 per patient with long-term mental illness for the intervention compared with the control.\n Significant differences were seen in relapse rates and practitioner satisfaction. Improvements in service development did not translate into documented improvements in care. This could be explained by the intervention working via the improvements in informal shared care developed through better link working. This type of facilitated intervention tailored to context has the potential to improve care and interface working.",
"Stresses imposed by parenthood can provoke or intensify relationship problems between parents. These problems, which are often associated with postnatal depression, can have serious consequences for family well-being but are often not revealed to primary health care personnel.\n To evaluate a means of extending the primary health care team's ability to identify and respond to relationship problems of mothers and their partners in the postnatal period.\n Cluster randomised controlled trial.\n Specially trained health visitors in nine 'intervention' clinics--each matched with a 'control' clinic' in an outer London borough.\n Health visitors in intervention clinics invited mothers attending for the six-to-eight-week developmental check to complete a screening scale for relationship problems, and offered help (supportive listening, advice, or referral) if needed. When visiting the clinic for the 12-week immunizations, mothers from all clinics were asked to complete a follow-up self-report questionnaire. After the completion of the trial, 25 women who had attended the intervention clinics and had been offered support with a relationship problem were interviewed to elicit their views on the acceptability and value of the intervention. All 25 of the health visitors engaged in the intervention were asked to complete a questionnaire on their experience.\n Screening led to striking differences between intervention and control clinics in the percentage of women identified at the six-to-eight-week check as potentially in need of help with a relationship problem (21% versus 5%, P = 0.007) and in the percentage actually offered help (18% versus 3%, P = 0.014). About one-half of the mothers so identified were also identified as having postnatal depression. At the 12-week visit for immunizations, the intervention group was twice as likely (P = 0.006) as the control group to report having discussed relationship problems with the health visitor and 75% more likely (P = 0.046) to report having received help with a problem.\n The intervention offers a useful way of extending the primary health care team's ability to respond to problems that often have serious consequences for family well-being.",
"To determine whether a new model of primary care, Chronic Care Clinics, can improve outcomes of common geriatric syndromes (urinary incontinence, falls, depressive symptoms, high risk medications, functional impairment) in frail older adults.\n Randomized controlled trial with 24 months of follow-up. Physician practices were randomized either to the Chronic Care Clinics intervention or to usual care.\n Nine primary care physician practices that comprise an ambulatory clinic in a large staff-model HMO in western Washington State.\n Those patients aged 65 and older in each practice with the highest risk for being hospitalized or experiencing functional decline.\n Intervention practices (5 physicians, 96 patients) held half-day Chronic Care Clinics every 3 to 4 months. These clinics included an extended visit with the physician and nurse dedicated to planning chronic disease management; a pharmacist visit that emphasized reduction of polypharmacy and high-risk medications; and a patient self-management/support group. Control practices (4 physicians, 73 patients) received usual care.\n Changes in self-reported urinary incontinence, frequency of falls, depressive symptoms, physical function, and satisfaction were analyzed using an intention-to-treat analysis adjusted for baseline differences, covariates, and practice-level variation. Prescriptions for high-risk medications and cost/utilization data obtained from administrative data were similarly analyzed.\n After 24 months, no significant improvements in frequency of incontinence, proportion with falls, depression scores, physical function scores, or prescriptions for high risk medications were demonstrated. Costs of medical care including frequency of hospitalization, hospital days, emergency and ambulatory visits, and total costs of care were not significantly different between intervention and control groups. A higher proportion of intervention patients rated the overall quality of their medical care as excellent compared with control patients (40.0% vs 25.3%, P = .10).\n Although intervention patients expressed high levels of satisfaction with Chronic Care Clinics, improved outcomes for selected geriatric syndromes were not demonstrated. These findings suggest the need for developing greater system-wide support for managing geriatric syndromes in primary care and illustrate the challenges of conducting practice improvement research in a rapidly changing delivery system.",
"To evaluate the effect of a combined or a single educational intervention on the prescribing behaviour of general practitioners (GPs). The primary endpoint was effect on inappropriate prescribing according to the Medication Appropriateness Index (MAI).\n General practitioners were randomised to either (1) a combined intervention consisting of an interactive educational meeting plus feedback on participating patients' medication, (2) a single intervention with an interactive educational meeting or (3) a control group (no intervention). Elderly (>65 years) patients exposed to polypharmacy (>or=5 medications) were identified and approached for inclusion. Data on medications prescribed over a 3-month period were collected, and the GPs provided detailed information on their patients before and after the intervention. A pre- and post-MAI were scored for all medications.\n Of the 277 GPs invited to participate; 41 (14.8%) volunteered. Data were obtained from 166 patients before and after the intervention. Medication appropriateness improved in the combined intervention group but not in the single intervention group. The mean change in MAI and number of medications was -5 [95% confidence interval (CI) -7.3 to -2.6] and -1.03 (95% CI -1.7 to -0.30) in the combined intervention group compared with the group with the educational meeting only and the no intervention group.\n A combined intervention consisting of an interactive educational meeting plus recommendations given by clinical pharmacologists/pharmacists concerning specific patients can improve the appropriateness of prescribing among elderly patients exposed to polypharmacy. This study adds to the limited number of well-controlled, randomised studies on overall medication appropriateness among elderly patients in primary care. Important limitations to the study include variability in data provided by participating GPs and a low number of GPs volunteering for the study.",
"Our professional development plan aimed to improve the primary care management of acute asthma, which is known to be suboptimal.\n We invited 59 general practices in Grampian, Scotland to participate. Consenting practices were randomised to early and delayed intervention groups. Practices undertook audits of their management of all acute attacks (excluding children under 5 years) occurring in the 3 months preceding baseline, 6-months and 12-months study time-points. The educational programme [including feedback of audit results, attendance at a multidisciplinary interactive workshop, and formulation of development plan by practice teams] was delivered to the early group at baseline and to the delayed group at 6 months. Primary outcome measure was recording of peak flow compared to best/predicted at 6 months. Analyses are presented both with, and without adjustment for clustering.\n 23 consenting practices were randomised: 11 to early intervention. Baseline practice demography was similar. Six early intervention practices withdraw before completing the baseline audit. There was no significant improvement in our primary outcome measure (the proportion with peak flow compared to best/predicted) at either the 6 or 12 month time points after adjustment for baseline and practice effects. However, the between group difference in the adjusted combined assessment score, whilst non-significant at 6 months (Early: 2.48 (SE 0.43) vs. Delayed 2.26 (SE 0.33) p = 0.69) reached significance at 12 m (Early:3.60 (SE 0.35) vs. Delayed 2.30 (SE 0.28) p = 0.02).\n We demonstrated no significant benefit at the a priori 6-month assessment point, though improvement in the objective assessment of attacks was shown after 12 months. Our practice development programme, incorporating audit, feedback and a workshop, successfully engaged the healthcare team of participating practices, though future randomised trials of educational interventions need to recognise that effecting change in primary care practices takes time. Monitoring of the assessment of acute attacks proved to be a feasible and responsive indicator of quality care.",
"To evaluate the effectiveness of a population based, multifaceted shared care intervention for late life depression in residential care.\n Randomised controlled trial, with control and intervention groups studied one after the other and blind follow up after 9.5 months.\n Population of residential facility in Sydney living in self care units and hostels.\n 220 depressed residents aged >/=65 without severe cognitive impairment.\n The shared care intervention included: (a) multidisciplinary consultation and collaboration, (b) training of general practitioners and carers in detection and management of depression, and (c) depression related health education and activity programmes for residents. The control group received routine care.\n Geriatric depression scale.\n Intention to treat analysis was used. There was significantly more movement to \"less depressed\" levels of depression at follow up in the intervention than control group (Mantel-Haenszel stratification test, P=0.0125). Multiple linear regression analysis found a significant intervention effect after controlling for possible confounders, with the intervention group showing an average improvement of 1.87 points on the geriatric depression scale compared with the control group (95% confidence interval 0.76 to 2.97, P=0.0011).\n The outcome of depression among elderly people in residential care can be improved by multidisciplinary collaboration, by enhancing the clinical skills of general practitioners and care staff, and by providing depression related health education and activity programmes for residents.",
"Only 3% of women with breast cancer participate in cancer clinical trials nationwide. The lack of awareness about clinical trials is a significant barrier towards clinical trials participation. A study was conducted at a large urban Comprehensive Cancer Center to test (1) the effectiveness of an 18-min educational video on improving attitudes toward clinical trials and trials enrollment among new breast cancer patients seen at the Karmanos Cancer Institute, and (2) to assess racial differences in attitudes regarding clinical trials. Participants were randomized to either the educational intervention prior to their first oncology clinic appointment or to standard care. A baseline and 2-week post-intervention survey to assess attitudes toward clinical trials participation was completed by participants. Of 218 subjects recruited, 196 (55% white vs. 45% African American (AA)) eligible patients were included in the analysis. A small increase in therapeutic clinical trial enrollment was observed in the intervention arm but was not statistically significant (10.4% vs. 6.1%; P = 0.277). The intervention also did not result in a clear improvement in patients' attitudes toward clinical trials at posttest. However, a lower enrollment rate for the AA women was noted after adjusting for stage (OR = 0.282, P = 0.049). Significantly more negative scores were noted in 3 out of the 5 baseline attitudinal scales for AA women. The educational video did not significantly increase enrollment in breast cancer clinical trials. The findings that AA women had significantly more negative attitudes toward clinical trials than white women may partially explain the racial disparity in enrollment. An educational video remains a simple and cost-effective way to educate patients. Future studies should focus on designing a new educational video to specifically target cultural and attitudinal barriers in the AA population to more effectively change attitudes and increase trial enrollment.",
"To test the effects of a computer-based nursing intervention designed to provide patients and family caregivers with concrete, objective information on symptom management; provide education about disease and treatment; coordinate medical resources; and provide emotional support and counseling.\n Two-site, randomized clinical trial.\n A large, urban, midwestern, tertiary-cancer center and a community-based cancer center in a medium-sized midwestern city.\n 109 patients newly diagnosed with breast, colon, or lung cancer who were receiving chemotherapy; 54 received standard care, and 55 participated in the intervention group.\n Outcome data were collected via structured telephone interviews at three time points: baseline, midway through the intervention, and one month postintervention. The intervention consisting of nine visits, five in person and four by telephone, was conducted over 18 weeks by advanced practice oncology nurses.\n Psychosocial functioning, anxiety, and depression.\n Patients who received the intervention had significantly less depression between baseline and the midway point, as well as less anxiety and greater improvement in the role-emotional and mental health subscales of the Medical Outcomes Study 36 Short Form.\n Cancer-care nursing interventions can decrease psychosocial morbidity and improve quality of life for newly diagnosed patients with cancer undergoing treatment. Additional research is needed to understand who benefited most from the intervention.\n This nurse-directed intervention resulted in improved mental health for patients; however, physical subscales were not changed. Further work is needed to determine why depression and mental health were affected yet physical health and symptoms did not differ between groups. Results support the important role of nurses in addressing mental health issues in patients and families experiencing cancer.",
"Major depression is a frequent and serious disorder in older medical inpatients. Because the condition goes undetected and untreated in most of these patients, we conducted a randomized clinical trial to evaluate the effectiveness of a strategy of systematic detection and multidisciplinary treatment of depression in this population.\n Consecutive patients aged 65 years or more admitted to general medical services in a primary care hospital between October 1999 and November 2002 were screened for depression with the Diagnostic Interview Schedule (DIS) within 48 hours after admission. Patients found to have major depression were randomly allocated to receive the intervention or usual care. The intervention involved consultation and treatment by a psychiatrist and follow-up by a research nurse and the patient's family physician. Research assistants, blind to group allocation, collected data from the patients at enrollment and at 3 and 6 months later using the Hamilton Depression Rating Scale (HAMD), the Medical Outcomes 36-item Short Form (SF-36), the DIS, the Mini-Mental State Examination (MMSE), the Older Americans Resources and Services (OARS) questionnaire to assess basic and instrumental activities of daily living (OARS-ADL and OARS-IADL) and the Rating Scale for Side Effects. Data on the severity of illness, length of hospital stay, health services and medication use, mortality and process of care were also collected. The primary outcome measures were the HAMD and SF-36.\n Of 1500 eligible patients who were screened, 157 were found to have major depression and consented to participate (78 in the intervention group and 79 in the usual care group). At randomization, there were no clinically or statistically significant differences between the 2 groups. Sixty-four patients completed follow-up to 6 months, 57 withdrew, and 36 died. At 6 months, there were no clinically or statistically significant differences the 2 groups in HAMD or SF-36 scores or any of the secondary outcome measures.\n We were unable to demonstrate that systematic detection and multidisciplinary care of depression was more beneficial than usual care for elderly medical inpatients.",
"We conducted a 4-year randomized study in a community health center that serves primarily low income Blacks in Durham, North Carolina. Patients (1318 at baseline) were assigned randomly to one of three study groups: provider prompting intervention alone, provider prompting and tailored print materials or the previous group and tailored telephone counseling. The purpose of the study was to determine whether increasingly intensive, tailored print and telephone interventions also were increasingly effective in promoting adherence to mammograms, Pap tests and overall cancer screening compliance. Thus, the combination of tailored print interventions (print and telephone) should have been more effective than the provider prompting intervention alone, or the print intervention and prompting combination. This is one of the few studies to examine a measure of overall cancer screening compliance and to assess the benefit of combinations of tailored interventions in promoting adherence to cancer screening. Patients gave extremely high ratings to the interventions. At the bivariate level, we found a significant effect of the most intensive group (provider prompting intervention, tailored print communications and tailored telephone counseling) on Pap test compliance (P = 0.05) and borderline significance at the multivariate level (P = 0.06) as well on overall screening compliance (P = 0.06). There was not a significant effect on mammography, probably because a majority of the patients were receiving regular mammograms. We also found some important subgroup differences. For example, a larger proportion of women reported Pap tests in the tailored print and counseling group when they believed the materials were 'meant for me.' These results show that a combination of tailored interventions may have potential for reaching the women who have too often been labeled the 'hard to reach.'",
"Many stroke patients and informal carers experience a decreased quality of life after discharge home and are dissatisfied with the care received. We assessed the effectiveness of an outreach nursing care program.\n In a multicenter trial, 536 stroke patients were randomized at discharge to standard care (n=273) or standard care plus outreach care (n=263). The outreach care consisted of 3 telephone calls and 1 home visit within 5 months after discharge by 1 of 13 stroke nurses. Patients were masked for the trial objectives. Six months after discharge, they assessed the 2 primary outcomes: quality of life (Short Form 36 [SF-36]) and dissatisfaction with care. Secondary measures of outcome were disability, handicap, depression, anxiety, and use of health care services and secondary prevention drugs. Informal carers assessed strain, and social support. Analysis was by intention to treat.\n Twelve patients died before follow-up, 38 declined outcome assessment, and 486 completed the primary outcome assessments. Outreach care patients had better scores on the SF-36 domain \"Role Emotional\" than controls (mean difference 7.9 [95% confidence limit, 0.1 to 15.7]). No statistically significant differences were found on the other primary outcome measures. For secondary outcomes, no statistically significant differences were found, except that intervention patients used fewer rehabilitation services (relative risk, 0.66 [0.44 to 1.00]) and had lower anxiety scores (median difference 1 [0.19 to 2.79]).\n This outreach nursing stroke care was not effective in improving quality of life and dissatisfaction with care of recently discharged patients.",
"Patient-centred depression care approaches should better address barriers of insufficient patient information and involvement in the treatment decision process. Additional research is needed to test the effect of increased patient participation on outcomes. The aim of this study was to assess, if patient participation in decision-making via a shared decision-making intervention leads to improved treatment adherence, satisfaction, and clinical outcome without increasing consultation time.\n Cluster-randomized controlled intervention study based on physician training and patient-centered decision aid compared to usual care in primary care settings in Südbaden region of Germany. Twenty-three primary care physicians treating 405 patients with newly diagnosed depression were enrolled. Patient involvement was measured with the patient perceived involvement in care scale (PICS) and a patient participation scale (MSH-scale). Patient satisfaction was measured by the CSQ-8 questionnaire. Treatment adherence was evaluated by patient and provider self-report. Depression severity and remission outcomes were assessed with the Brief PHQ-D.\n Physician facilitation of patient participation improved significantly and to a greater extent in the intervention compared to the control group. There was no intervention effect for depression severity reduction. Doctor facilitation of patient participation, patient-rated involvement, and physician assessment of adherence improved only in the intervention group. Patient satisfaction at post-intervention was higher in the intervention group compared to the control group. The consultation time did not differ between groups.\n A shared decision-making intervention was better than usual care for improving patient participation in treatment decision-making, and patient satisfaction without increasing consultation time. Additional research is needed to model causal linkages in the decision-making process in regard to outcomes.\n The study results encourage the implementation of patient participation in primary care of depression."
] |
Because of the inclusion of multiple interventions in most studies, the determination of the effect of any single intervention is difficult. Although there is evidence of limited benefit of developmental care interventions overall, and no major harmful effects reported, there were a large number of outcomes for which no or conflicting effects were demonstrated. The single trials that did show a significant effect of an intervention on a major clinical outcome were based on small sample sizes, and the findings were often not supported in other small trials.
Before a clear direction for practice can be supported, evidence demonstrating more consistent effects of developmental care interventions on important short- and long-term clinical outcomes is needed. The economic impact of the implementation and maintenance of developmental care practices should be considered by individual institutions.
|
CD008567
|
[
"15113492",
"12689976",
"19664653"
] |
[
"Exploratory cluster randomised controlled trial of shared care development for long-term mental illness.",
"Effectiveness of counselling patients on physical activity in general practice: cluster randomised controlled trial.",
"Five years of lifestyle intervention improved self-reported mental and physical health in a general population: the Inter99 study."
] |
[
"Primary care clinicians have a considerable amount of contact with patients suffering from long-term mental illness. The United Kingdom's National Health Service now requires general practices to contribute more systematically to care for this group of patients.\n To determine the effects of Mental Health Link, a facilitation-based quality improvement programme designed to improve communication between the teams and systems of care within general practice. Design of study: Exploratory cluster randomised controlled trial.\n Twenty-three urban general practices and associated community mental health teams.\n Practices were randomised to service development as usual or to the Mental Health Link programme. Questionnaires and an audit of notes assessed 335 patients' satisfaction, unmet need, mental health status, processes of mental and physical care, and general practitioners' satisfaction with services and beliefs about service development. Service use and intervention costs were also measured.\n There were no significant differences in patients' perception of their unmet need, satisfaction or general health. Intervention patients had fewer psychiatric relapses than control patients (mean = 0.39 versus 0.71, respectively, P = 0.02) but there were no differences in documented processes of care. Intervention practitioners were more satisfied and services improved significantly for intervention practices. There was an additional mean direct cost of pound 63 per patient with long-term mental illness for the intervention compared with the control.\n Significant differences were seen in relapse rates and practitioner satisfaction. Improvements in service development did not translate into documented improvements in care. This could be explained by the intervention working via the improvements in informal shared care developed through better link working. This type of facilitated intervention tailored to context has the potential to improve care and interface working.",
"To assess the long term effectiveness of the \"green prescription\" programme, a clinician based initiative in general practice that provides counselling on physical activity.\n Cluster randomised controlled trial. Practices were randomised before systematic screening and recruitment of patients.\n 42 rural and urban general practices in one region of New Zealand.\n All sedentary 40-79 year old patients visiting their general practitioner during the study's recruitment period.\n General practitioners were prompted by the patient to give oral and written advice on physical activity during usual consultations. Exercise specialists continued support by telephone and post. Control patients received usual care.\n Change in physical activity, quality of life (as measured by the \"short form 36\" (SF-36) questionnaire), cardiovascular risk (Framingham and D'Agostino equations), and blood pressure over a 12 month period.\n 74% (117/159) of general practitioners and 66% (878/1322) of screened eligible patients participated in the study. The follow up rate was 85% (750/878). Mean total energy expenditure increased by 9.4 kcal/kg/week (P=0.001) and leisure exercise by 2.7 kcal/kg/week (P=0.02) or 34 minutes/week more in the intervention group than in the control group (P=0.04). The proportion of the intervention group undertaking 2.5 hours/week of leisure exercise increased by 9.72% (P=0.003) more than in the control group (number needed to treat=10.3). SF-36 measures of self rated \"general health,\" \"role physical,\" \"vitality,\" and \"bodily pain\" improved significantly more in the intervention group (P<0.05). A trend towards decreasing blood pressure became apparent but no significant difference in four year risk of coronary heart disease.\n Counselling patients in general practice on exercise is effective in increasing physical activity and improving quality of life over 12 months.",
"Self-reported health has been shown to predict mortality. We lack knowledge on whether a lifestyle intervention can improve self-reported mental and physical health in a general population.\n Inter99, Denmark (1999-2006) is a randomised population-based intervention study. We screened for ischemic heart disease and repeatedly offered advice and assistance to obtain a healthier lifestyle. Health related quality of life was measured by Short Form 12 (SF-12); completed by 9322 at baseline and 7719 at five-year follow-up. In linear mixed models we investigated the effect of the intervention on self-reported health over time.\n At baseline men had higher physical health-component scores (PCS) than women. Living with a partner, being employed, and being healthy was associated with high PCS. The mental health-component scores (MCS) showed the same socio-demographic differences, except that MCS increased with age. Significantly fewer participants in the intervention groups had decreased their PCS and MCS compared with the control group. Adjusted multilevel analyses confirmed that the intervention significantly improved physical- (p=0.008) and mental health (p<0.001) over time compared with the control group.\n Screening for ischemic heart disease and offering lifestyle intervention had a significantly beneficial effect on mental and physical self-reported health in the long term in a general population."
] |
General physical health could lead to people with serious mental illness accessing more health services which, in turn, could mean they see longer term benefits such as reduced mortality or morbidity. On the other hand it is possible clinicians are expending much effort, time and financial expenditure on giving ineffective advice. This is an important area for good research reporting outcome of interest to carers and people with serious illnesses as well as researchers and fundholders.
Note: the 43 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.
|
CD003952
|
[
"812052",
"6472970",
"22664861"
] |
[
"Nasoduodenal versus nasogastric feeding in the very low birthweight infant.",
"An investigation into the benefits of resiting nasoenteric feeding tubes.",
"Randomized controlled trial of slow vs rapid enteral feeding advancements on the clinical outcomes of preterm infants with birth weight 750-1250 g."
] |
[
"The practicality, effectiveness, and safety of feeding very low birthweight infants (less than 1,300 gm) by continuous nasoduodenal infusion was assessed by comparison with continuous nasogastric feeding. The nasoduodenal group appeared to have a clear advantage over the nasogastric group for the overall period in terms of caloric intake (131 cal/kg/day vs. 106 cal/kg/day), average weight gain (16 gm/day vs. 10 gm/day), and safety. This advantage was even more striking in the first two weeks of life. A caloric intake of 120 cal/kg/day could be reached within 48 to 72 hours after tube placement in the nasoduodenal group but only after a week in the nasogastric group. Nasoduodenal feeding resulted in faster weight gain than comparable published data on conventional feeding, peripheral intravenous alimentation, and parenteral alimentation. There were no cases of aspiration associated with tubes placed in the duodenum whereas two cases of aspiration pneumonia were associated with tubes placed in the stomach. With the tip of the catheter in the duodenum, none of the complications reported with nasojejunal tubes (intussusception, perforation, or necrotizing enterocolitis) were seen, either in the initial pilot study reported here or in 50 additional infants.",
"Partial nasal obstruction in preterm infants increases the airway resistance. In spite of this, nasal feeding tubes are often used, if only because oral tubes are difficult to secure. A palatal appliance has been devised that maintains the position of oroenteric feeding tube(s) and is not associated with local complications. In order to assess the effects of resiting feeding tubes, two related studies were carried out. The first study, a trial, included respiratory monitoring of 29 infants on the third and/or seventh day after either the appliance and oroenteric tubes had been inserted, or, in the control group, after the nasoenteric tubes had been passed. After seven days, the infants using the palatal appliance had significantly less periodic breathing, central apnea, and movement than the control group. The second study showed that the removal of feeding tubes that had been in situ for several days reduced apnea rates and produced a significant increase in transcutaneous PO2.",
"To evaluate the effect of slow vs rapid rates of advancement of enteral feed volumes on the clinical outcomes in preterm infants with 750-1250 g birth weight.\n A total of 92 stable neonates 750-1250 g and gestational age <32 weeks were randomly allocated to enteral feeding advancement of 20 mL/kg/d (n = 46) or 30 mL/kg/d (n = 46). The primary outcome was days to reach full enteral feeding, defined as 180 mL/kg/d. Secondary outcomes included rates of necrotizing enterocolitis (NEC) and culture-proven sepsis, days of parenteral nutrition (PN), length of hospital stay, and growth end points.\n Neonates in the rapid-feeding advancement group achieved full enteral volume of feedings earlier than the slower advancement group. They received significantly fewer days of PN, exhibited a shorter time to regain birth weight, and had a shorter duration of hospital stay. The incidence of NEC and the number of episodes of feeding intolerance were not significantly different between the groups, whereas the incidence of culture-proven late-onset sepsis was significantly less in infants receiving a rapid feeding advancement. Excluding infants who were small for gestational age at birth, the incidence of extrauterine growth restriction was significantly reduced in the rapid-advancement group at 28 days and at hospital discharge.\n Rapid enteral feeding advancements in 750-1250 g birth weight infants reduce the time to reach full enteral feeding and the use of PN administration. Rapid-advancement enteral feed also decreases extrauterine growth restriction with improved short-term outcomes for these high-risk infants."
] |
There are insufficient data available to inform practice. A large randomised controlled trial would be required to determine if the use of naso- versus oro-enteric feeding tubes affects feeding, growth and development, and the incidence of adverse events in preterm or low birth weight infants.
|
CD005967
|
[
"21062666",
"12830403",
"20850004",
"9231212",
"16125588",
"1287904"
] |
[
"Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial.",
"Randomized comparison of artesunate and quinine in the treatment of severe falciparum malaria.",
"Comparison of artesunate and quinine in the treatment of Sudanese children with severe Plasmodium falciparum malaria.",
"Comparison of artemisinin suppositories, intramuscular artesunate and intravenous quinine for the treatment of severe childhood malaria.",
"Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial.",
"Comparison of artemisinin suppositories with intravenous artesunate and intravenous quinine in the treatment of cerebral malaria."
] |
[
"Severe malaria is a major cause of childhood death and often the main reason for paediatric hospital admission in sub-Saharan Africa. Quinine is still the established treatment of choice, although evidence from Asia suggests that artesunate is associated with a lower mortality. We compared parenteral treatment with either artesunate or quinine in African children with severe malaria.\n This open-label, randomised trial was undertaken in 11 centres in nine African countries. Children (<15 years) with severe falciparum malaria were randomly assigned to parenteral artesunate or parenteral quinine. Randomisation was in blocks of 20, with study numbers corresponding to treatment allocations kept inside opaque sealed paper envelopes. The trial was open label at each site, and none of the investigators or trialists, apart from for the trial statistician, had access to the summaries of treatment allocations. The primary outcome measure was in-hospital mortality, analysed by intention to treat. This trial is registered, number ISRCTN50258054.\n 5425 children were enrolled; 2712 were assigned to artesunate and 2713 to quinine. All patients were analysed for the primary outcome. 230 (8·5%) patients assigned to artesunate treatment died compared with 297 (10·9%) assigned to quinine treatment (odds ratio [OR] stratified for study site 0·75, 95% CI 0·63-0·90; relative reduction 22·5%, 95% CI 8·1-36·9; p=0·0022). Incidence of neurological sequelae did not differ significantly between groups, but the development of coma (65/1832 [3·5%] with artesunate vs 91/1768 [5·1%] with quinine; OR 0·69 95% CI 0·49-0·95; p=0·0231), convulsions (224/2712 [8·3%] vs 273/2713 [10·1%]; OR 0·80, 0·66-0·97; p=0·0199), and deterioration of the coma score (166/2712 [6·1%] vs 208/2713 [7·7%]; OR 0·78, 0·64-0·97; p=0·0245) were all significantly less frequent in artesunate recipients than in quinine recipients. Post-treatment hypoglycaemia was also less frequent in patients assigned to artesunate than in those assigned to quinine (48/2712 [1·8%] vs 75/2713 [2·8%]; OR 0·63, 0·43-0·91; p=0·0134). Artesunate was well tolerated, with no serious drug-related adverse effects.\n Artesunate substantially reduces mortality in African children with severe malaria. These data, together with a meta-analysis of all trials comparing artesunate and quinine, strongly suggest that parenteral artesunate should replace quinine as the treatment of choice for severe falciparum malaria worldwide.\n The Wellcome Trust.\n Copyright © 2010 Elsevier Ltd. All rights reserved.",
"A randomized, open-label comparison of artesunate and quinine was conducted in 113 adults with clinically severe falciparum malaria in western Thailand. Mortality was 12% with artesunate and 22% with quinine treatment (relative risk, 0.53; 95% confidence interval, 0.23-1.26; P=.22). Multiple logistic regression analysis found admission plasma lactate level, Glasgow Coma Scale score, and total serum bilirubin level to be independent risk factors for death. Coma recovery and times to normalize plasma lactate levels were similar, but the parasite clearance time was much shorter among artesunate-treated patients (P=.019). Fewer patients became hypoglycemic during artesunate therapy (10%) than during quinine therapy (28%) (P=.03). Artesunate is at least as effective as quinine in the treatment of adults with severe malaria. Larger trials are required to determine whether mortality is reduced among patients treated with artesunate.",
"Sixty-six children presenting to Singa hospital, Sudan with different manifestations of severe Plasmodium falciparum malaria were randomly divided into two well-matched groups (33 in each arm) to receive either intravenous artesunate 2·4 mg/kg at 0, 12, and 24 hours, then daily, or intravenous quinine 20mg/kg initially then 10mg/kg three times a day. There was no significant difference in the fever, parasite clearance, and coma resolution times. Three patients died, one in the artesunate and two in the quinine groups. One patient developed hypoglycaemia following quinine infusion. Thus, artesunate can be used for the treatment of severe falciparum malaria.\n Copyright © 2010 Royal Society of Tropical Medicine and Hygiene.",
"Severe malaria remains a major cause of mortality and morbidity for children living in many tropical regions. With the emergence of strains of Plasmodium falciparum resistant to both chloroquine and quinine, alternative antimalarial agents are required. The artemisinin group of compounds are rapidly effective in severe disease when given by intramuscular or intravenous injection. However, these routes of administration are not always available in rural areas. In an open, randomized comparison 109 Vietnamese children, aged between 3 months and 14 years, with severe P.falciparum malaria, were allocated at random to receive artemisinin suppositories followed by mefloquine (n = 37), intramuscular artesunate followed by mefloquine (n = 37), or intravenous quinine followed by pyrimethamine/sulfadoxine (n = 35). There were 9 deaths: 2 artemisinin, 4 artesunate and 5 quinine-treated children. There was no difference in fever clearance time, coma recovery, or length of hospital stay among the 3 groups. However, parasite clearance times were significantly faster in artemisinin and artesunate-treated patients than in those who received quinine (P < 0.0001). Both artemisinin and artesunate were very well tolerated, but children receiving these drugs had lower peripheral reticulocyte counts by day 5 of treatment than those in the quinine group (P = 0.011). No other adverse effect or toxicity was found. There was no treatment failure in these 2 groups, but 4 patients in the quinine group failed to clear their parasites within 7 d of starting treatment and required alternative antimalarial therapy. Artemisinin suppositories are easy to administer, cheap, and very effective for treating children with severe malaria. In rural areas where medical facilities are lacking these drugs will allow antimalarial therapy to be instituted earlier in the course of the disease and may therefore save lives.",
"In the treatment of severe malaria, intravenous artesunate is more rapidly acting than intravenous quinine in terms of parasite clearance, is safer, and is simpler to administer, but whether it can reduce mortality is uncertain.\n We did an open-label randomised controlled trial in patients admitted to hospital with severe falciparum malaria in Bangladesh, India, Indonesia, and Myanmar. We assigned individuals intravenous artesunate 2.4 mg/kg bodyweight given as a bolus (n=730) at 0, 12, and 24 h, and then daily, or intravenous quinine (20 mg salt per kg loading dose infused over 4 h then 10 mg/kg infused over 2-8 h three times a day; n=731). Oral medication was substituted when possible to complete treatment. Our primary endpoint was death from severe malaria, and analysis was by intention to treat.\n We assessed all patients randomised for the primary endpoint. Mortality in artesunate recipients was 15% (107 of 730) compared with 22% (164 of 731) in quinine recipients; an absolute reduction of 34.7% (95% CI 18.5-47.6%; p=0.0002). Treatment with artesunate was well tolerated, whereas quinine was associated with hypoglycaemia (relative risk 3.2, 1.3-7.8; p=0.009).\n Artesunate should become the treatment of choice for severe falciparum malaria in adults.",
"Seventy-nine comatose cerebral malaria patients given standard supportive treatment were randomized to receive specific antimalarial chemotherapy of intravenous quinine, intravenous artesunate, or artemisinin suppositories. Artesunate and artemisinin reduced peripheral asexual parasitaemia significantly more rapidly than quinine (90% clearance time 16 h, 18.9 h and 34.5 h respectively), but did not significantly reduce the duration of coma or mortality. The rapid lowering of peripheral parasitaemia may not ameliorate complications already present. These results demonstrate that artemisinin suppositories are as effective as artesunate and quinine given intravenously, and have economic and practical advantages for the treatment of severe malaria in areas remote from major medical centres. However, large numbers of patients will need to be studied if differences in mortality between the 3 treatment groups are to be demonstrated."
] |
The evidence clearly supports the superiority of parenteral artesunate over quinine for the treatment of severe malaria in both adults and children and in different regions of the world.
|
CD002843
|
[
"15166533",
"18176319",
"1445500",
"9722821",
"17321948",
"18645518",
"11157288",
"1905051"
] |
[
"Effect of brief safer-sex counseling by medical providers to HIV-1 seropositive patients: a multi-clinic assessment.",
"Effects of a coping intervention on transmission risk behavior among people living with HIV/AIDS and a history of childhood sexual abuse.",
"Results of a randomized trial of partner notification in cases of HIV infection in North Carolina.",
"The outreach-assisted model of partner notification with IDUs.",
"Intervening with couples: assessing contraceptive outcomes in a randomized pregnancy and HIV/STD risk reduction intervention trial.",
"Clinic-based intervention reduces unprotected sexual behavior among HIV-infected patients in KwaZulu-Natal, South Africa: results of a pilot study.",
"An evaluation of a system-change training model to improve emergency department response to battered women.",
"Building skills of recovering women drug users to reduce heterosexual AIDS transmission."
] |
[
"To test the efficacy of brief, safer-sex counseling by medical providers of HIV-positive patients during medical visits.\n Six HIV clinics in California.\n Clinics were randomized to intervention arms evaluated with cohorts of randomly selected patients measured before and after the intervention.\n Five-hundred and eighty-five HIV-positive persons, sexually active prior to enrollment.\n Prevention counseling from medical providers supplemented with written information. Two clinics used a gain-framed approach (positive consequences of safer-sex), two used a loss-frame approach (negative consequences of unsafe sex), and two were attention-control clinics (medication adherence). Interventions were given to all patients who attended the clinics.\n Self-reported unprotected anal or vaginal intercourse (UAV).\n Among participants who had two or more sex partners at baseline, UAV was reduced 38% (P < 0.001) among those who received the loss-frame intervention. UAV at follow-up was significantly lower in the loss-frame arm [odds ratio (OR), 0.42; 95% confidence interval (CI), 0.19-0.91; P = 0.03] compared with the control arm. Using generalized estimating equations (GEE) to adjust for clustering did not change the conclusions (OR, 0.34; 95% CI, 0.24-0.49; P = 0.0001). Similar results were obtained in participants with casual partners at baseline. No effects were seen in participants with only one partner or only a main partner at baseline. No significant changes were seen in the gain-frame arm.\n Brief provider counseling emphasizing the negative consequences of unsafe sex can reduce HIV transmission behaviors in HIV-positive patients presenting with risky behavioral profiles.",
"To examine the effect of a 15-session coping group intervention compared with a 15-session therapeutic support group intervention among HIV-positive men and women with a history of childhood sexual abuse (CSA) on sexual transmission risk behavior.\n A randomized controlled behavioral intervention trial with 12-month follow-up.\n A diverse sample of 247 HIV-positive men and women with histories of CSA was randomized to 1 of 2 time-matched group intervention conditions. Sexual behavior was assessed at baseline; immediately after the intervention; and at 4-, 8-, and 12-month follow-up periods (5 assessments). Changes in frequency of unprotected anal and vaginal intercourse by intervention condition were examined using generalized linear mixed models for all partners, and specifically for HIV-negative or serostatus unknown partners.\n Participants in the HIV and trauma coping intervention condition decreased their frequency of unprotected sexual intercourse more than participants in the support intervention condition for all partners (P < 0.001; d = 0.38, 0.32, and 0.38 at the 4-, 8-, and 12-month follow-up periods, respectively) and for HIV-negative and serostatus unknown partners (P < 0.001; d = 0.48, 0.39, and 0.04 at the 4-, 8-, and 12-month follow-up periods, respectively).\n A group intervention to address coping with HIV and CSA can be effective in reducing transmission risk behavior among HIV-positive men and women with histories of sexual trauma.",
"We sought to compare two methods of notifying sex partners of subjects infected with the human immunodeficiency virus (HIV) or persons who had shared needles with them (needle-sharing partners): \"patient referral,\" in which the responsibility for notifying partners was left to the patient, and \"provider referral,\" in which providers attempted to notify partners.\n Names of sex partners and needle-sharing partners and information on how to locate them were obtained from consenting HIV-infected subjects identified in the HIV-testing programs at three public health departments in North Carolina. The subjects were randomly assigned to a patient-referral group (in which patients had the initial responsibility for notifying their partners) or a provider-referral group (in which the study counselor notified the partners). The success of attempts to notify partners was monitored by means of interviews with counselors conducted both in the field and at the health department.\n Of 534 HIV-positive persons identified at the health departments, 247 (46 percent) did not return for counseling after the test, 8 were counseled outside the study, and 117 (22 percent) were ineligible. Of the 162 invited to participate, 88 (54 percent) declined and 74 (46 percent) agreed. The subjects were mostly male (69 percent), black (87 percent), homosexual or bisexual (76 percent of the men), and had a median age of 30 years. Thirty-nine were assigned to the provider-referral group and 35 to the patient-referral group. In the provider-referral group 78 of 157 partners (50 percent) were successfully notified, whereas in the patient-referral group only 10 of 153 (7 percent) were notified. Of the partners notified by the counselors, 94 percent were not aware that they had been exposed to HIV. Overall, 23 percent of the partners notified and tested were HIV-positive.\n In this trial, leaving the notification of partners up to the subjects (patient referral) was quite ineffective, despite the North Carolina law requiring that partners be notified. Partner notification by public health counselors (provider referral) was significantly more effective. Although the effectiveness of notification procedures is constrained by the accuracy of the information provided by HIV-infected patients, counselors who notify the partners of an infected patient can refer them to educational, medical, and support services targeted to persons at high risk for HIV infection and may encourage the adoption of less risky behavior.",
"This analysis describes the Outreach-Assisted Model of Partner Notification, an innovative strategy for encouraging seropositive injecting drug users (IDUs) to inform their partners of shared human immunodeficiency virus (HIV) exposure. The analysis focuses on two core components of the notification process: the identification of at-risk partners and preferences for self-tell vs. outreach assistance in informing partners of possible exposure to the virus.\n Using community outreach techniques, 386 IDUs were recruited for HIV pretest counseling, testing, and partner notification over a 12-month period. Of these, 63 tested HIV seropositive, and all but three returned for their test results. The 60 who were informed of their serostatus were randomly assigned to either a minimal or an enhanced intervention condition. Participants assigned to the minimal (self-tell) group were strongly encouraged to inform their partners of possible exposure. Those assigned to the enhanced (outreach-assisted) group had the option of either informing one or more of their partner(s) themselves or choosing to have the project's outreach team do so.\n Together, the 60 index persons who received their results provided names or at least one piece of locating information for a total of 142 partners with whom they perceived having shared possible exposure to the virus within the past five years. By itself, drug use accounted for half of all partners named. Sexual behavior alone accounted for 25% of named partners. Eighty-two percent of the enhanced group preferred to have the outreach team tell at least one partner; the team was requested to notify 71% of the total number of partners whom this group named.\n Findings suggest that IDUs want to notify their partners of shared HIV exposure. Outreach assistance was the preferred mode in the majority of cases. Expanding traditional community-based HIV outreach activities to include delivering street-based counseling, test, a partner notification appears to be a positive and workable prevention strategy.",
"This study assessed the contraceptive outcomes of the Partners Against Risk-Taking: A Networking, Evaluation and Research Study (PARTNERS). The PARTNERS project developed and evaluated a 3-session intervention to help young women and their male partners reduce their risk for unintended pregnancies, and HIV and other STDs.\n Participating couples were randomly assigned to the 3-session intervention or a 1-session information session for couples. Changes in psychosocial factors related to women's motivation to use contraception and relationship factors were assessed using analysis of variance with repeated measures. Changes in contraceptive outcomes were assessed using logistic regression with generalized estimating equations.\n Comparison of changes from baseline to 6 months among women who participated in the 3-session intervention with those who participated in the information session showed no significant intervention effect on reports of contraceptive use. Instead, contraceptive use increased in both conditions. Both groups exhibited similar changes in the psychosocial variable measuring the importance of avoiding pregnancy and in the relationship variable measuring women's participation in contraceptive decision making. Members of the intervention group, however, showed greater improvement in the psychosocial variable measuring positive expectations pertaining to partner's support for contraception.\n These findings raise questions for further investigation to better understand couples behavior, and whether and how to intervene with couples.",
"To evaluate the feasibility, fidelity, and effectiveness of a human immunodeficiency virus (HIV) prevention intervention delivered to HIV-infected patients by counselors during routine clinical care in KwaZulu-Natal, South Africa.\n A total of 152 HIV-infected patients, aged 18 years and older, receiving clinical care at an urban hospital in South Africa, were randomly assigned to intervention or standard-of-care control counselors. Intervention counselors implemented a brief risk reduction intervention at each clinical encounter to help patients reduce their unprotected sexual behavior. Self-report questionnaires were administered at baseline and 6 months to assess number of unprotected sex events in previous 3 months.\n Intervention was delivered in 99% of routine patient visits and included a modal 8 of 8 intervention steps. Although HIV-infected patients in both conditions reported more vaginal and anal sex events at 6-month follow-up than at baseline, patients who received the counselor-delivered intervention reported a significant decrease over time in number of unprotected sexual events. There was a marginally significant increase in these events among patients in the standard-of-care control condition.\n A counselor-delivered HIV prevention intervention targeting HIV-infected patients seems to be feasible to implement with fidelity in the South African clinical care setting and effective at reducing unprotected sexual behavior.",
"To evaluate a system-change model of training from the Family Violence Prevention Fund and the Pennsylvania Coalition Against Domestic Violence for improving the effectiveness of emergency department (ED) response to intimate partner violence (IPV).\n An experimental design with outcomes measured at baseline, 9-12, and 18-24 months post-intervention. Twelve hospitals in Pennsylvania and California with 20,000-40,000 annual ED visits were randomly selected and randomly assigned to experimental and control conditions. Emergency department teams (physician, nurse, social worker) from each experimental hospital and a local domestic violence advocate participated in a two-day didactic information and team planning intervention.\n The experimental hospitals were significantly higher than the control hospitals on a staff knowledge and attitude measure (F = 5.57, p = 0.019), on all components of the \"culture of the ED\" system-change indicator (F = 5.72, p = 0.04), and in patient satisfaction (F = 15.43, p < 0.001) after the intervention. There was no significant difference in the identification rates of battered women (F = 0.411, p = 0.52) (although the linear comparison was in the expected direction) in the medical records of the experimental and control hospitals.\n A system-change model of IPV ED training was effective in improving staff attitudes and knowledge about battered women and in protocols and staff training, as well as patient information and satisfaction. However, change in actual clinical practice was more difficult to achieve and may be influenced by institutional policy.",
"Although most women infected with HIV are intravenous drug users, some contact the virus through sexual contact with IV drug users. To reach at-risk women, public health officials must develop a range of prevention strategies. One approach, skills training, holds promise as a means of altering risk-related sexual behavior. In this study, 91 women methadone patients were pretested and randomly assigned to an information-only control control group or a skills-building intervention group. Skills-building intervention consisted of five sessions of small groups in which participants identified their own high risk sexual behaviors, discussed their negative associations with condoms, and practiced skills which involved asking partners to use condoms. Compared with members of the control group, respondents in the intervention group reported that they initiated discussion of sexual issues with their partners more frequently, felt more comfortable talking with them about safer sex, and reported using and carrying condoms more frequently. The high rates of attendance and program retention by skills-building participants suggest that such groups may be supportive and useful in the design of risk reduction and drug abuse treatment programs. The modest outcomes of this study underscore the difficulty of altering risk behavior but also serve as a basis for future AIDS prevention studies."
] |
There is a need for evaluations of interventions combining provider training and patient education, and for evaluations conducted in developing countries. All partner notification evaluations, but especially those among HIV positive patients, need to measure potential harmful effects, such as domestic violence, to ensure that partner notification does more good than harm.
|
CD008319
|
[
"6408619",
"18716688"
] |
[
"Efficacy of inhaled tobramycin in the treatment of pulmonary exacerbations in children with cystic fibrosis.",
"A pilot study to compare tobramycin 80 mg injectable preparation with 300 mg solution for inhalation in cystic fibrosis patients."
] |
[
"Two forms of treatment of acute pulmonary exacerbations in patients with cystic fibrosis were compared: intravenous ticarcillin (300 mg drug per kg per day) and tobramycin (10 mg drug per kg per day) versus the same intravenous antibiotic therapy plus inhaled tobramycin (80 mg three times per day). The 16 patients in the intravenous plus inhaled tobramycin group were similar to the 12 control patients in age, sex, Schwachman scores, pulmonary function and pretreatment colony counts of Pseudomonas aeruginosa in sputum. Treatment resulted in significant improvement in clinical status and pulmonary function without any apparent differences in the two groups. However, intravenous plus inhaled tobramycin resulted in temporary eradication of P. aeruginosa in 63% of the patients compared to 25% in the intravenous only group (P = 0.03). Suppression of P. aeruginosa in sputum cultures did not correlate with clinical response to treatment. No renal toxicity or elevations of serum tobramycin were observed in the intravenous plus inhaled tobramycin group.",
"Inhaled tobramycin has been shown to improve lung function in cystic fibrosis (CF) patients chronically infected with Pseudomonas aeruginosa. However, to date no comparative data are available for different dose regimens used in clinical practice.\n To compare the clinical efficacy of the two most commonly used treatment regimens of inhaled tobramycin in patients with CF.\n In an open crossover study of CF patients, subjects were randomly allocated to receive either 80 mg tobramycin twice-daily continuous treatment or 300 mg tobramycin twice daily in cycles of 28 days on and 28 days off treatment. After three months, patients were switched to the alternative treatment regimen.\n A total of 32 patients with a mean (+/- SD) age of 18.5+/-8.6 years were included in the study. Compared with the treatment period using colistin, forced expiratory volume in 1 s decreased by -2.1+/-13.8% in the 80 mg tobramycin group and increased by +2.3+/-13.0% in the 300 mg group. Similar changes were observed in forced vital capacity (-2.5+/-12.9% in the 80 mg tobramycin group versus +2.5+/-9.6% in the 300 mg tobramycin group). Variability in responses was large but the differences were not statistically significant. Personal preference indicated that the majority of patients preferred the high-dose cycle compared with the lower dose continuous inhalation, but this was not linked to objective data on efficacy.\n The present trial fails to provide convincing evidence for superiority in efficacy of either of the two treatment regimens of inhaled tobramycin in CF patients."
] |
There is little useful high-level evidence to judge the effectiveness of inhaled antibiotics for the treatment of pulmonary exacerbations in people with cystic fibrosis. The included trials were not sufficiently powered to achieve their goals. Hence, we are unable to demonstrate whether one treatment was superior to the other or not. Further research is needed to establish whether inhaled tobramycin may be used as an alternative to intravenous tobramycin for some pulmonary exacerbations.
|
CD008231
|
[
"1460211",
"7751531",
"2557947",
"12134249",
"11554655",
"6452842",
"9063425"
] |
[
"A double-blind, placebo-controlled study of the safety and efficacy of ipratropium bromide nasal spray versus placebo in patients with the common cold.",
"A dose-response study of the efficacy and safety of ipratropium bromide nasal spray in the treatment of the common cold.",
"Evaluation of an alpha agonist alone and in combination with a nonsteroidal antiinflammatory agent in the treatment of experimental rhinovirus colds.",
"Combined antiviral-antimediator treatment for the common cold.",
"The therapeutic effectiveness of ibuprofen on the symptoms of naturally acquired common colds.",
"Ipratropium nasal spray: a new treatment for rhinorrhea in the common cold.",
"Is an antihistamine-decongestant combination effective in temporarily relieving symptoms of the common cold in preschool children?"
] |
[
"Ipratropium bromide (IB) has been found to reduce secretions in the upper respiratory tract; this is accomplished through competitive inhibition of acetylcholine at muscarinic receptors that control rhinorrhea production. This study compared the safety and efficacy of IB with placebo in the symptomatic relief of rhinorrhea in patients with the common cold. Human subjects with symptoms of a common cold, primarily rhinorrhea, were enrolled and treated with either IB (84 micrograms/nostril) or placebo; each was administered as two sprays per nostril, four times a day, for 4 days. Primary efficacy analyses were in-clinic measurements of nasal discharge weights over a 3-hour period after administration on days 1 and 2 and assessment of rhinorrhea symptoms by use of a subjective patient-completed visual analog rating scale. IB significantly reduced rhinorrhea an average of 18% over placebo for days 1 and 2 (p = 0.01). Visual analog scale scores showed an average improvement in rhinorrhea of 22% over placebo (p = 0.001). When patients with relatively minor rhinorrhea (baseline weight of nasal discharge < or = 1.0 gm) were excluded, IB produced an average reduction in nasal discharge of 23% over placebo for days 1 and 2 (p = 0.003).",
"Rhinorrhea is an annoying symptom of the common cold for which effective therapy is not currently available. Ipratropium bromide (IB) is an anticholinergic drug that has been shown to decrease glandular secretion when applied topically to the nasal mucosa. The purpose of this study was to compare the efficacy and safety of three doses of IB nasal spray versus either vehicle or no treatment in relieving rhinorrhea in patients with naturally acquired colds. Rhinorrhea severity was measured objectively by determining nasal discharge weights and subjectively by means of visual analog scale scores. Compared with either vehicle or no treatment, IB nasal spray produced a significant decrease in the severity of rhinorrhea. A dose of 84 micrograms (two sprays of a 0.06% solution in buffered saline solution) in each nostril was more efficacious than a 42 microgram per nostril dose and only marginally less efficacious than a 168 micrograms per nostril dose. The 84 micrograms per nostril dose also was associated with fewer adverse events than was the higher dose. None of the adverse events related to intranasal IB therapy was of a serious nature. The use of IB nasal spray appears to be a rational and safe approach to relieving rhinorrhea associated with the common cold.",
"The pathogenesis of symptoms of the common cold and their optimal treatment are incompletely understood. To evaluate the role of an oral alpha agonist alone and in combination with a nonsteroidal anti-inflammatory drug in the treatment of experimental rhinovirus colds, 58 subjects were randomized to receive pseudoephedrine 60 mg alone, pseudoephedrine 60 mg plus ibuprofen 200 mg, or placebo, four times daily for 4 1/2 days beginning 30 hours after intranasal rhinovirus inoculation under double-blind conditions. The frequencies of infection, colds occurrence, and viral shedding did not differ significantly between the groups. Total symptom scores were reduced by 59% by pseudoephedrine plus ibuprofen (p less than 0.05) and 48% by pseudoephedrine alone compared with placebo. Nasal symptom scores tended to be lower in recipients of pseudoephedrine plus ibuprofen compared with pseudoephedrine alone (p = 0.09), but other parameters showed no significant treatment differences between the groups. Rhinorrhea, as determined by nasal secretion weights, was significantly reduced in both treatment groups compared to placebo. Nasal patency measurements tended to show the greatest improvement in recipients of pseudoephedrine plus ibuprofen. Therapy was clinically well tolerated. The results suggest that an oral alpha agonist is effective in modifying certain manifestations of experimental rhinovirus infection and that the addition of a nonsteroidal anti-inflammatory drug may provide additional benefit in nasal symptoms and patency. Studies involving large numbers of patients with natural colds are needed to determine the clinical significance of these findings.",
"A randomized, controlled, double-masked clinical trial was conducted with a combination antiviral-antimediator treatment for experimental rhinovirus colds. In all, 150 healthy men and women (aged 18-51 years) were randomly assigned to 1 of 3 groups: intranasal interferon (IFN)-alpha2b (6 x 10(6) U every 12 h x 3) plus oral chlorpheniramine (12 mg extended release) and ibuprofen (400 mg) every 12 h for 4.5 days (n=59 subjects); intranasal placebo plus oral chlorpheniramine and ibuprofen (n=61 subjects); or intranasal and oral placebos (n=30 subjects). Treatment was started 24 h after intranasal viral challenge. During the 4.5 days of treatment with IFN-alpha2b, chlorpheniramine, and ibuprofen, the daily mean total symptom score was reduced by 33%-73%, compared with placebo. Treatment reduced the severity of rhinorrhea, sneezing, nasal obstruction, sore throat, cough, and headache and reduced nasal mucus production, nasal tissue use, and virus concentrations in nasal secretions. IFN-alpha2b added to the effectiveness of chlorpheniramine and ibuprofen and was well tolerated.",
"The pathogenesis of the common cold is associated with inflammation of the nasal mucous membrane with polymorphonuclear cells (PMNs)(1,2) and increased levels of inflammatory cytokines and mediators in nasal secretions.(3,4) We have investigated the effect of a nonsteroidal anti-inflammatory drug (NSAID) ibuprofen, 400 mg three times daily, in a placebo-controlled trial of 80 adults with naturally occurring common colds. Ibuprofen caused a significant reduction of headache (p = 0.008), earache (p = 0.01), muscle/joint pain (p = 0.045), and reduced body temperature (p = 0.02). There was a 40% reduction in the number of sneezes (p = 0.02) and a 33% reduction in the symptom score for sneezing (p = 0.04). This study did not detect any effect on other nasal symptoms.",
"A need is often present for symptomatic treatment of the common cold. A blocked nose can be opened by a vasoconstrictor, but no effective therapy is known today for rhinorrhea. The aim of the present trial was to study the effect of the topically active parasympatholytic, ipratropium, on rhinorrhea. In a placebo-controlled group comparative trial, 80 micrograms of ipratropium were taken as a nasal spray 4 times daily for 1 wk by 40 adults with spontaneously occurring common colds. All subjects administered an intranasal vasoconstrictor (xylomethazoline, 0.1%) 5 min before administering placebo or ipratropium. Ipratropium treatment resulted in a significant reduction in nasal discharge compared with that of placebo treatment during the whole treatment period (p less than 0.001), but the drug was especially effective the first 3 days, when the watery secretion was predominant. It was concluded that this new spray can be of value in the first days of a cold, when nasal discharge is a nuisance.",
"To determine whether an antihistamine-decongestant combination (ADC) is superior to placebo in temporarily relieving symptoms of upper respiratory tract infection (URI) in preschool children.\n Randomized, double-blind, placebo-controlled trial.\n Four pediatric offices in the Seattle, Wash, area.\n Children 6 months through 5 years of age with a URI of less than 7 days' duration.\n Children were randomly assigned to receive an ADC (brompheniramine maleate-phenylpropanolamine hydrochloride) or placebo as needed for URI symptoms. Two hours after each dose of study medication, changes in the child's runny nose, nasal congestion, cough, and sleep status were assessed by means of a standardized questionnaire.\n A total of 175 responses were recorded for 59 patients. There were no statistically significant differences in symptom improvement between the ADC and the placebo group (runny nose, p = 0.48; nasal congestion, p = 0.94; cough, p = 0.66). However, the proportion of children asleep 2 hours after receiving the ADC was significantly higher than the proportion receiving placebo (46.6% vs 26.5%; p = 0.01). Results were unchanged after control for the correlated nature of repeated responses, age, symptom duration, use of acetaminophen, time that the medication was given, and parental desire for medication.\n The ADC was equivalent to placebo in providing temporary relief of URI symptoms in preschool children. However, the ADC did have significantly greater sedative effects than did placebo."
] |
For people with the common cold, the existing evidence, which has some limitations, suggests that IB is likely to be effective in ameliorating rhinorrhoea. IB had no effect on nasal congestion and its use was associated with more side effects compared to placebo or no treatment although these appeared to be well tolerated and self limiting. There is a need for larger, high-quality trials to determine the effectiveness of IB in relieving common cold symptoms.
|
CD004352
|
[
"11585480",
"12196868",
"6988006",
"11530870",
"12165579",
"16846587",
"10329891",
"15925046"
] |
[
"Single vs weekly courses of antenatal corticosteroids for women at risk of preterm delivery: A randomized controlled trial.",
"Multiple versus single courses of antenatal corticosteroids for preterm birth: a pilot study.",
"The influence of betamethasone and orciprenaline on the incidence of respiratory distress syndrome in the newborn after preterm labour.",
"The effect of antenatal corticosteroid therapy on pregnancies complicated by premature rupture of membranes.",
"The effect of a single remote course versus weekly courses of antenatal corticosteroids on functional residual capacity in preterm infants: a randomized trial.",
"Single versus weekly courses of antenatal corticosteroids: evaluation of safety and efficacy.",
"Corticosteroid therapy for prevention of respiratory distress syndrome in severe preeclampsia.",
"Antenatal corticosteroid therapy: a comparative study of dexamethasone and betamethasone effects on fetal Doppler flow velocity waveforms."
] |
[
"The practice of administering weekly courses of antenatal corticosteroids to pregnant women at risk of preterm delivery is widespread, but no randomized trial has established the efficacy or safety of this practice.\n To evaluate the efficacy of weekly administration of antenatal corticosteroids compared with a single course in reducing the incidence of neonatal morbidity and to evaluate potential complications of weekly treatment.\n Randomized, double-blind, placebo-controlled intention-to-treat trial conducted in 13 academic centers in the United States from February 1996 through April 2000.\n A total of 502 pregnant women between 24 and 32 completed weeks' gestation who were at high risk of preterm delivery.\n All patients received a complete single course of antenatal corticosteroids (either betamethasone, 12 mg intramuscularly repeated once in 24 hours for 2 doses, or dexamethasone, 6 mg intramuscularly repeated every 12 hours for 4 doses). Participants who had not delivered 1 week after receipt of the single course were randomly assigned to receive either betamethasone, 12 mg intramuscularly repeated once in 24 hours for 2 doses every week until 34 weeks' gestation or delivery, whichever came first (n = 256), or a similarly administered placebo (n = 246).\n Composite neonatal morbidity (including severe respiratory distress syndrome, bronchopulmonary dysplasia, severe intraventricular hemorrhage, periventricular leukomalacia, proven sepsis, necrotizing enterocolitis, or perinatal death).\n Composite morbidity occurred in 22.5% of the weekly-course group vs 28.0% of the single-course group (unadjusted relative risk, 0.80; 95% confidence interval, 0.59-1.10). Neither group assignment nor the number of treatment courses was associated with a reduction in composite morbidity.\n Weekly courses of antenatal corticosteroids did not reduce composite neonatal morbidity compared with a single course of treatment. Weekly courses of antenatal corticosteroids should not be routinely prescribed for women at risk of preterm delivery.",
"(1) To determine the feasibility of a multicentre, randomized, double-masked, placebo-controlled trial to investigate the effects of multiple courses of antenatal corticosteroids (ACS), more than 7 days following the initial course of ACS therapy, on perinatal or neonatal mortality or neonatal morbidity. (2) To determine the risk of complications that would require discontinuation of ACS therapy. (3) To determine if multiple courses of ACS have an effect on the concentrations of plasma cortisol and adrenocorticotropin hormone (ACTH) in cord blood and in maternal blood immediately following delivery, compared to a single course of ACS.\n Women at 24 to 30 weeks' gestation, at continued increased risk of preterm birth 7 or more days following a single course of ACS, were randomized to receive weekly courses of betamethasone or placebo until 33 weeks' gestation or delivery.\n Women were recruited at two hospitals in Toronto from 01 September 1999 to 31 August 2000. Of the 78 women who were approached and were eligible for the study, 12 (15%) were recruited and 66 (85%) refused to participate. Of the 66 refusals, 38 (58%) did not feel their physicians were supportive of the study, 10 (15%) did not want to be randomized, and 4 (6%) had other personal reasons for refusing to enter the trial. Fourteen women (21%) had physicians who did not allow them to join the study. The lack of physician support was due to concerns related to the potential adverse effects of multiple courses of ACS. There were no complications requiring discontinuation of ACS. Plasma cortisol and ACTH concentrations in cord and maternal blood taken after delivery were not significantly different between ACS and placebo groups.\n A multicentre randomized controlled trial is required to determine the benefits and risks of multiple versus a single course of ACS. If the study protocols are supported by physicians and their patients, a multicentre randomized controlled trial is feasible.",
"In a randomized double-blind trial on antenatal corticosteroid treatment for the prevention of respiratory distress syndrome (RDS) a corticosteroid related beneficial effect was found. Possibly of more significance was the finding that the children born within 12 hours of their mother's admission to hospital showed a higher incidence of RDS than those born between 12 hours and one week after admission even in the placebo and untreated groups. Bèta-adrenergic drugs seemed to exert no other influence on the occurrence of RDS than can be explained by the delay of delivery. Prolonged ruptured membranes appeared to decrease the incidence of RDS to the same extent as other symptoms of threatened preterm labour.",
"This study was carried out to examine the effect of antenatal corticosteroid therapy on pregnancies complicated by premature rupture of membranes (PROMs). For this purpose, 139 patients with a singleton pregnancy (27-34 weeks of gestation) complicated by PROMs were evaluated prospectively during the period January 1997 to February 1999 at two Jordanian military hospitals (Prince Rhashed and Prince Zaid). Patients were allocated into two groups; Group 1 included 72 patients treated with dexamethsone (24 mg divided into 4 doses 12 hours apart), and Group 2 which included 67 patients whoreceived no treatment (control group). All women were examined clinically and the diagnosis of PROMs was demonstrated using vaginal speculum, nitrazine paper examination and ultrasonography. All neonates were evaluated clinically, radiologically, and by laboratory investigations. Pearson's Chi-square and Fisher's exact tests were used to assess the significance of differences between the two study groups. Respiratory distress syndrome (RDS), necrotizing enterocolitis (NEC), intraventricular haemorrhage (IVH), and days of hospital stay were significantly reduced in premature infants of the corticosteroid treated women compared with the controls (p<0.04, p<0.04, p<0.04, and p<0.05, respectively). The perinatal mortality was significantly decreased among the corticosteroid treated group in the gestational subgroups 31-32 and 33-34 weeks (p<0.04), and in all birth weight subgroups (p<0.03). RDS was statistically a significant factor which resulted in increased perinatal mortality in the control group (p=0.02). Regarding the occurrence of postpartum endometritis there was a statistically significant increase among the corticosteroid treated group compared with the controls (p<0.04). Conclusion: Antenatal corticosteroid therapy in pregnancies complicated by PROMs has a positive influencing effect on premature infants between 31 and 34 weeks of gestation, decreasing significantly the perinatal morbidity and mortality. It should be used with particular relevance to the developing world where surfactant is not available or where neonatal intensive care units are lacking.",
"There are no randomized data on the effect of repeat courses of corticosteroids during pregnancy on newborn pulmonary function. Our objective was to compare the effect of a single remote course of antenatal steroids (AS) with weekly courses of AS on functional residual capacity (FRC) and respiratory compliance in preterm infants.\n Pregnant women 25 to 33 weeks' gestation, who remained undelivered 1 week after their first course of antenatal corticosteroids (two 12-mg doses of betamethasone) were randomized to weekly courses of corticosteroids versus weekly placebo until delivery or 34 weeks' gestation. FRC was measured with the nitrogen washout technique and respiratory compliance with the single breath occlusion technique within 48 hours of life.\n Thirty-seven infants (mean gestational age at delivery approximately 32.5 weeks) were studied. Maternal and infant demographics were similar. There was no significant difference in FRC (28.5 vs 27.5 mL/kg) or respiratory compliance between the infants who received a single remote course of antenatal corticosteroids and those who received weekly courses of corticosteroids until delivery. There was no significant difference in admission head circumference or birth weights between the groups.\n Our results demonstrate that weekly repetitive courses of AS do not significantly increase FRC or respiratory compliance in preterm infants when compared with a single remote course of steroids given at a mean gestational age of 29 weeks.",
"The purpose of this study was to determine if weekly corticosteroids improve neonatal outcome without undue harm.\n Women 23 to 32 weeks receiving 1 course of corticosteroids 7 to 10 days prior were randomized to weekly betamethasone or placebo.\n The study was terminated by the independent data and safety monitoring committee with 495 of the anticipated 2400 patients enrolled. There was no significant reduction in the composite primary morbidity outcome (8.0% vs 9.1%, P = .67). Repeated courses significantly reduced neonatal surfactant administration (P = .02), mechanical ventilation (P = .004), CPAP (P = .05), pneumothoraces (P = .03). There was no significant difference in mean birth weight or head circumference. The repeat group had a reduction in multiples of the birth weight median by gestational age (0.88 vs 0.91) (P = .01) and more neonates weighing less than the 10th percentile (23.7 vs 15.3%, P = .02). Significant weight reductions occurred for the group receiving > or = 4 courses.\n Repeat antenatal corticosteroids significantly reduce specific neonatal morbidities but do not improve composite neonatal outcome. This is accompanied by reduction in birth weight and increase in small for gestational age infants.",
"The objective of the study was to determine the efficacy and side effects of corticosteroid therapy for pregnant women with severe preeclampsia in the prevention of respiratory distress syndrome in their premature neonates.\n A prospective double-blind randomized trial enrolled 218 pregnant women with severe preeclampsia and gestational age between 26 and 34 weeks. One hundred ten received betamethasone (12 mg administered intramuscularly, repeated after 24 hours and then once a week) and 108 received placebo. Relative risks and 95% confidence intervals of respiratory distress syndrome and other neonatal and maternal complications were calculated for corticosteroid use.\n Frequency of respiratory distress syndrome was significantly reduced in the corticosteroid group (23%) with respect to the placebo group (43%), with a relative risk of 0.53 (95% confidence interval 0.35-0. 82). Relative risks of intraventricular hemorrhage, patent ductus arteriosus, and perinatal infection were significantly decreased in the corticosteroid group: 0.35 (95% confidence interval 0.15-0.86), 0.27 (95% confidence interval 0.08-0.95), and 0.39 (95% confidence interval 0.39-0.97), respectively. There was no significant difference in the frequency of stillbirth, but the neonatal mortality rate was lower in the corticosteroid group (14%) than in the placebo group (28%), with a relative risk of 0.5 (95% confidence interval 0.28-0.89). There was increased risk of gestational diabetes but of no other maternal complication after corticosteroid therapy, and mean blood pressures were similar in the 2 groups.\n Antenatal corticosteroid therapy with betamethasone for acceleration of fetal lung maturity is a safe and efficient treatment in patients with severe preeclampsia at between 26 and 34 weeks' gestation.",
"To compare the effects of antenatal administration of dexamethasone and betamethasone, used in two different regimens, on fetal Doppler flow velocities.\n Sixty-seven women at risk for preterm delivery received course of corticosteroids by means of a computer-generated randomization table. The Doppler examination of the pulsatility index (PI) of the umbilical artery (UA), the middle cerebral artery (MCA) and the middle cerebral artery/umbilical artery PI ratio (MCA PI/UA PI) were performed before treatment, 24 and 72 h after the first dose of corticosteroids. The SAS system was used to perform statistical analysis.\n No significant change was observed in UA PI through dexamethasone therapy. In MCA there was a significant decrease in PI at 72 h (2+/-0.43 before and 1.68+/-0.31 after, p=0.0001). Similarly a significant decrease in MCA PI/UA PI ratio was noted (2.09+/-0.51 before and 1.83+/-0.4 after, p=0.0137). No significant changes were observed in UA PI, MCA PI and MCA PI/UA PI ratio during betamethasone treatment.\n Our results indicate significant decrease in fetal middle cerebral artery impedance at 72 h after maternal administration of the first dose of dexamethasone. Effects of dexamethasone on fetal brain warrants further research."
] |
Betamimetics help to delay delivery for women transferred to tertiary care or completed a course of antenatal corticosteroids. However, multiple adverse effects must be considered. The data are too few to support the use of any particular betamimetics.
[Note: The 14 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]
|
CD005340
|
[
"19577277",
"8088611",
"10343192",
"11146078",
"16153694",
"16394300",
"6796106",
"11181662"
] |
[
"Importance of delivered cycles and nomogram for intraperitoneal chemotherapy in ovarian cancer.",
"A comparison of intravenous versus intraperitoneal chemotherapy for the initial treatment of ovarian cancer.",
"A comparative study of intraperitoneal carboplatin versus intravenous carboplatin with intravenous cyclophosphamide in both arms as initial chemotherapy for stage III ovarian cancer.",
"Intraperitoneal cisplatin-based chemotherapy vs. intravenous cisplatin-based chemotherapy for stage III optimally cytoreduced epithelial ovarian cancer.",
"Randomized trial of adjuvant intraperitoneal alpha-interferon in stage III ovarian cancer patients who have no evidence of disease after primary surgery and chemotherapy: An intergroup study.",
"Intraperitoneal cisplatin and paclitaxel in ovarian cancer.",
"Medical Research Council study on chemotherapy in advanced ovarian cancer. Medical Research Council's Working Party on ovarian cancer.",
"Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group."
] |
[
"Intraperitoneal (IP) chemotherapy has gained enthusiasm in the treatment of ovarian cancer. Despite having a better survival advantage than intravenous (IV) chemotherapy, IP chemotherapy still poses significant morbidity and complications. Identifying the subset of patients who could best benefit from IP chemotherapy, and those who would least benefit from this treatment, thus avoiding potential complications, is critical.\n Between January 2001 and December 2007, 367 patients with stage III epithelial ovarian cancer underwent randomized trial for IP/IV chemotherapy were recruited to construct a nomogram, which is a graphical representation of Cox proportional hazards model adopting six weighted risk factors including age, CA125, IP/IV delivery, stage, histology, and upper abdominal metastases. The nomogram was internally validated for discrimination and calibration. The concordance index was used for quantifying the predictive ability of overall survival with bootstrapping to correct for bias.\n The cycles of completed IP chemotherapy had an impact on overall survival (> or =5 vs. < or =4 cycles, P=0.02). A nomogram for predicting median survival and 5-year survival probability was constructed with a concordance index of 0.72. Upper abdominal tumor metastases (P<0.001) and colon resection (P=0.02) predicted increased chances for early discontinuation of IP chemotherapy.\n At least five IP cycles are needed to achieve better survival. Nomogram can help to identify the subset of patients who can least benefit from IP chemotherapy, thus avoiding potential IP complications and help to facilitate discussion between patient and physician, risk stratification, and help to guide clinical care.",
"A phase III study was conducted comparing intraperitoneal (ip) versus intravenous (iv) cisplatin-based therapy for patients with newly diagnosed ovarian cancer to determine if the pharmacologic advantage of ip delivery could be translated into an improved response and survival rate. Twenty-nine patients were randomized to receive six cycles of ip cisplatin 200 mg/m2 plus ip etoposide 350 mg/m2 with iv thiosulfate protection given every 4 weeks; thirty-three patients were randomized to receive six cycles of iv cisplatin 100 mg/m2 plus iv cyclophosphamide 600 mg/m2 administered every 3 weeks. Patients were stratified by stage (IIC-IV) and size of residual disease (> or < or = 1 cm). The study was conducted in a community-wide setting. The complete response in evaluable patients was 48% in the ip group and 52% in the iv group. The surgical complete response rate for all patients on study, underestimated because not all patients in complete clinical remission had a second-look laparotomy, was 31% in the ip group and 33% in the iv group. There was no difference in the response rates between the treatment arms as a function of residual disease < or = or > 1 cm. With a median follow-up of 46 months (range 21-70 months) there is no difference in response duration or survival. Both regimens were well tolerated with comparable hematologic and nonhematologic toxicity.",
"Cisplatin (C) or carboplatin (CBP) plus cyclophosphamide (CTX) was until recently considered standard chemotherapy for advanced ovarian cancer (OC). Attempts to maximize platinum and its analog activity against OC include its administration directly into the peritoneal cavity. In the past we have shown that intraperitoneal (IP) CBP administration is a safe and effective treatment for OC [Polyzos et al: Proc Am Assoc Cancer Res 1990;31: 1120]. In the present study we aimed to compare the effectiveness and toxicity of CBP administration either intravenously (IV) or IP plus CTX IV. Since 1990, 90 evaluable patients with stage III OC were prospectively randomized to receive CBP 350 mg/m2 IV or IP plus CTX 600 mg/m2 IV (in both groups) every 3-4 weeks for six courses. The randomization incorporated stratification according to performance status and the amount of residual tumor (maximum diameter </=2 or >2 cm). Clinical assessment was performed with abdominal CT and serum CA-125. Responses were observed in 33/46 = 72% (95/CI 56.5-84.0) of the IV group and in 33/44 = 75% (95/CI 59.7-86.8) of the IP group with 48 and 45% clinical complete responses, respectively. Times to progression were 19 months (8-62+) for the IV group and 18 (6-72+) for the IP group. Median survivals were: 25 months (6-80+) and 26 months (6-72+), respectively. Significantly more patients in the IV group than in the IP group had grade 3 or higher leukopenia (p < 0. 01) and grade 3 thrombocytopenia (p < 0.09). Morbidity due to infectious complications in the IP group was minimal. It seems that IP CBP is equally effective to IV administration in terms of response and survival with less myelotoxicity. The favorable results on survival demonstrated in studies with IP C administration in patients with small volume disease [Alberts et al: N Engl J Med 1996;335:1950-1965] could not be repeated in the present study applying CBP in patients with variable tumor size and a relatively small number of patients. The likelihood that patients with large volume disease would benefit from a regional approach compared to systemic administration is small and this explains the inability to detect a difference between the two arms.",
"To compare the survival between intraperitoneal cisplatin-based chemotherapy (IPCT) and intravenous cisplatin-based chemotherapy (IVCT) in stage III epithelial ovarian cancer with minimal residual disease (<1 cm) after primary debulking surgery.\n One hundred and thirty-two patients with stage III epithelial ovarian cancer after optimal primary debulking surgery with minimal residual disease between April 1990 and March 1995 were entered into a randomized clinical trial in which IPCT or IVCT was administered at 3-week intervals. Patients in the IPCT arm received cisplatin-based (100 mg/m(2)) intraperitoneal chemotherapy. Patients in the IVCT arm received cisplatin-based (50 mg/m(2)) intravenous chemotherapy. The tumor response was assessed every 3 months. The hematological toxicity using the South West Oncology Group (SWOG) toxicity criteria was assessed. Catheter complications associated with intraperitoneal chemotherapy were also analyzed.\n The estimated median survival in the IPCT group was 43 months (95% confidence interval, 34-54) and IVCT group was 48 months (95% confidence interval, 37-59). The hazard ratio of death was not statistically significant between IPCT and IVCT (hazard ratio, 1.13; 95% CI, 0.69-1.86; P=0.317). The frequencies of hematological toxic effects were significantly lower in the IPCT group than in the IVCT group.\n Intravenous and intraperitoneal chemotherapy are associated with equivalent survival in patients with minimal residual stage III epithelial ovarian cancer after optimal cytoreductive surgery.",
"Despite the improvement in progression-free and overall survival in patients with advanced ovarian cancer associated with platinum-taxane chemotherapy, strategies are needed to prevent the greater than 70% recurrence rate.\n The Southwest Oncology Group (SWOG) initiated a phase III intergroup trial of alpha-interferon (IFNalpha-26, Schering-Plough, Kenilworth, NJ) in weekly doses of 50 x 10(6) IU (for 6 doses) versus observation only in patients with no pathological evidence of residual disease at second-look surgery in 1988.\n Patient accrual was extremely slow and the trial was permanently closed in 1999 by the SWOG Data and Safety Monitoring Committee with 74 registered patients. Of these patients, 70 were evaluable for progression-free and overall survival. There was no significant difference between the two study arms in relation to median progression-free survival (P = 0.56). The median survival duration associated with intraperitoneal alpha-interferon had not been reached versus 87 months on the observation arm. In general, intraperitoneal alpha-interferon was well tolerated. There were no treatment-related deaths or grade 4 adverse events. Although no efficacy conclusions can be drawn from this prematurely closed trial, it should be noted that 57% of the patients on the observation arm recurred and all died, whereas 63% recurred and only 43% died on the intraperitoneal alpha-interferon arm.\n Although this was a negative study, there should continue to be interest in the use of biological therapy to improve survival of patients in complete remission following primary chemotherapy.",
"Standard chemotherapy for newly diagnosed ovarian cancer is a platinum-taxane combination. The Gynecologic Oncology Group conducted a randomized, phase 3 trial that compared intravenous paclitaxel plus cisplatin with intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel in patients with stage III ovarian cancer.\n We randomly assigned patients with stage III ovarian carcinoma or primary peritoneal carcinoma with no residual mass greater than 1.0 cm to receive 135 mg of intravenous paclitaxel per square meter of body-surface area over a 24-hour period followed by either 75 mg of intravenous cisplatin per square meter on day 2 (intravenous-therapy group) or 100 mg of intraperitoneal cisplatin per square meter on day 2 and 60 mg of intraperitoneal paclitaxel per square meter on day 8 (intraperitoneal-therapy group). Treatment was given every three weeks for six cycles. Quality of life was assessed.\n Of 429 patients who underwent randomization, 415 were eligible. Grade 3 and 4 pain, fatigue, and hematologic, gastrointestinal, metabolic, and neurologic toxic effects were more common in the intraperitoneal-therapy group than in the intravenous-therapy group (P< or =0.001). Only 42 percent of the patients in the intraperitoneal-therapy group completed six cycles of the assigned therapy, but the median duration of progression-free survival in the intravenous-therapy and intraperitoneal-therapy groups was 18.3 and 23.8 months, respectively (P=0.05 by the log-rank test). The median duration of overall survival in the intravenous-therapy and intraperitoneal-therapy groups was 49.7 and 65.6 months, respectively (P=0.03 by the log-rank test). Quality of life was significantly worse in the intraperitoneal-therapy group before cycle 4 and three to six weeks after treatment but not one year after treatment.\n As compared with intravenous paclitaxel plus cisplatin, intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel improves survival in patients with optimally debulked stage III ovarian cancer.\n Copyright 2006 Massachusetts Medical Society.",
"A total of 264 eligible patients with advanced ovarian cancer were randomised to single or triple agent cytotoxic therapy; 261 were available for analysis. The treatments were continuous oral cyclophosphamide (arm S), and a combination of oral cyclophosphamide, hexamethylmelamine and methotrexate on a pulsed basis (arm T). Mortality attributed to cancer was slightly lower on arm T (p = 0.06), but this was offset by the greater toxicity of this regimen, and overall survival and activity index were similar on the two arms. There was thus little evidence of greater clinical benefit on the triple agent regimen. Tumour mass removed at operation, extent of remaining tumour and age all showed significant correlation with prognosis. Survival was longer in patients whose disease responded to either therapeutic regimen.",
"To compare the progression-free and overall survival in small-volume residual ovarian cancer after treatment with intravenous (IV) cisplatin and paclitaxel or an experimental regimen of IV carboplatin followed by IV paclitaxel and intraperitoneal cisplatin.\n Patients were randomized to receive either IV paclitaxel 135 mg/m(2) over 24 hours followed by IV cisplatin 75 mg/m(2) every 3 weeks for six courses or IV carboplatin (area under curve 9) every 28 days for two courses, then IV paclitaxel 135 mg/m(2) over 24 hours followed by intraperitoneal (IP) cisplatin 100 mg/m(2) every 3 weeks for six courses.\n Of the 523 patients who entered this trial, 462 were determined to be assessable, with prognostic factors well balanced between the treatments. Neutropenia, thrombocytopenia, and gastrointestinal and metabolic toxicities were greater in the experimental arm. As a result, 18% of the patients received < or = two courses of IP therapy. Progression-free survival was superior for patients randomized to the experimental treatment arm (median, 28 v 22 months; relative risk, 0.78; log-rank P =.01, one-tail). There was a borderline improvement in overall survival associated with this regimen (median, 63 v 52 months; relative risk, 0.81; P =.05, one-tail).\n An experimental regimen including moderately high-dose IV carboplatin followed by IP paclitaxel and IV cisplatin yielded a significant improvement in progression-free survival when compared with a standard regimen of IV cisplatin and paclitaxel. Because the improvement in overall survival was of borderline statistical significance and toxicity was greater, the experimental arm is not recommended for routine use. However, the results provide direction for further clinical investigation in small-volume ovarian cancer."
] |
Intraperitoneal chemotherapy increases overall survival and progression-free survival from advanced ovarian cancer. The results of this meta-analysis provide the most reliable estimates of the relative survival benefits of IP over IV therapy and should be used as part of the decision making process. However, the potential for catheter related complications and toxicity needs to be considered when deciding on the most appropriate treatment for each individual woman. The optimal dose, timing and mechanism of administration cannot be addressed from this meta-analysis. This needs to be addressed in the next phase of clinical trials.
|
CD006787
|
[
"9349677",
"8684391",
"17426347",
"8503751",
"15839735"
] |
[
"Rhythmic facilitation of gait training in hemiparetic stroke rehabilitation.",
"Rhythmic auditory stimulation in gait training for Parkinson's disease patients.",
"Rhythmic auditory stimulation improves gait more than NDT/Bobath training in near-ambulatory patients early poststroke: a single-blind, randomized trial.",
"Task-specific physical therapy for optimization of gait recovery in acute stroke patients.",
"The effects of music on pain perception of stroke patients during upper extremity joint exercises."
] |
[
"Experimental and control groups of 10 hemiparetic stroke patients each underwent a 6 week, twice daily gait training program. The control group participated in a conventional physical therapy gait program. The experimental group trained in the same basic program with the addition of rhythmic auditory stimulation (RAS). Patients entered the study as soon as they could complete 5 strides with hand-held assistance. The training program had to be completed within 3 months of the patients' stroke. In the experimental group RAS was used as a timekeeper to synchronize step patterns and gradually entrain higher stride frequencies. Study groups were equated by gender, lesion site, and age. Motor function was assessed at pretest using Barthel, Fugl-Meyer, and Berg Scales. Walking patterns were assessed during pre- and post-test without RAS present. Pre- vs post-test measures revealed a statistically significant (P<0.05) increase in velocity (164% vs 107%), stride length (88% vs 34%), and reduction in EMG amplitude variability of the gastrocnemius muscle (69% vs 33%) for the RAS-training group compared to the control group. The difference in stride symmetry improvement (32% in the RAS-group vs 16% in the control group) was statistically not significant. The data offer evidence that RAS is an efficient tool to enhance efforts in gait rehabilitation with acute stroke patients.",
"Rhythmic auditory stimulation (RAS) was used as a pacemaker during a 3-week home-based gait-training program for Parkinson's disease (PD) patients (n = 15). Electromyogram (EMG) patterns and stride parameters were assessed before and after the test without RAS to evaluate changes in gait patterns. Data were compared with those of two control groups (n = 11), who either did not participate in any gait training or who participated in an internally self-paced training program. RAS consisted of audiotapes with metronome-pulse patterns embedded into the on/off beat structure of rhythmically accentuated instrumental music. Patients who trained with RAS significantly (p < 0.05) improved their gait velocity by 25%, stride length by 12%, and step cadence by 10% more than self-paced subjects who improved their velocity by 7% and no-training subjects whose velocity decreased by 7%. In the RAS-group, timing of EMG patterns changed significantly (p < 0.05) in the anterior tibialis and vastus lateralis muscles. Evidence for rhythmic entrainment of gait patterns was shown by the ability of the RAS group to reproduce the speed of the last training tape within a 2% margin of error without RAS.",
"The effectiveness of 2 different types of gait training in stroke rehabilitation, rhythmic auditory stimulation (RAS) versus neurodevelopmental therapy (NDT)/Bobath- based training, was compared in 2 groups of hemiparetic stroke patients over a 3-week period of daily training (RAS group, n = 43; NDT/Bobath group =35).\n Mean entry date into the study was 21.3 days poststroke for the RAS group and 22.3 days for the control group. Patients entered the study as soon as they were able to complete 5 stride cycles with handheld assistance. Patients were closely equated by age, gender, and lesion site. Motor function in both groups was pre-assessed by the Barthel Index and the Fugl-Meyer Scales.\n Pre- to posttest measures showed a significant improvement in the RAS group for velocity (P = .006), stride length (P = .0001), cadence (P = .0001) and symmetry (P = .0049) over the NDT/Bobath group. Effect sizes for RAS over NDT/Bobath training were 13.1 m/min for velocity, 0.18 m for stride length, and 19 steps/min for cadence.\n The data show that after 3 weeks of gait training, RAS is an effective therapeutic method to enhance gait training in hemiparetic stroke rehabilitation. Gains were significantly higher for RAS compared to NDT/Bobath training.",
"A randomized controlled pilot trial was conducted to estimate the effects of early, intensive, gait-focused physical therapy on ambulatory ability in acute, stroke patients. Twenty-seven patients with middle cerebral artery infarct of thromboembolic origin confirmed by computed axial tomography scan were stratified and randomly assigned to the experimental group, to a control group that received early, intensive and conventional therapy, or to a group receiving routine conventional therapy that started later and was not intense. Assessments at entry, six weeks, and three and six months by independent evaluators permitted comparisons with reference to clinical measures of motor performance, balance, and functional capacity, and laboratory measures of gait movements. Group results at six weeks demonstrated that gait velocity was similar in the two conventional groups thereby eliminating the timing of the interventions as an important factor. At that point, gait velocity was faster in the experimental group. The difference translated into a moderate effect size of 0.58. The time dedicated to gait training but not to total therapy time was correlated (rs = 0.63) to gait velocity. This effect disappeared at three and six months after stroke. These pilot results justify planning a large trial to test the effectiveness of a therapeutic protocol that focuses on early and intense gait therapy in an effort to facilitate early ambulation following stroke.",
"The purpose of this study was to determine the effects of music therapy on pain perception of stroke patients during upper extremity joint exercises. Ten stroke patients (1 male and 9 females) ranging in age from 61 to 73 participated in the study. Music conditions used in the study consisted of: (a) song, (b) karaoke accompaniment (same music to condition A except singers' voices), and (c) no music. Exercise movements in this study included hand, wrist, and shoulder joints. During the 8-week period music therapy sessions, subjects repeated 3 conditions according to the randomized orders and subjects rated their perceived pain on a scale immediately after each condition. The General Linear Model (GLM) Repeated Measures ANOVA revealed that there were no significant differences in pain rating across the three music conditions. However, positive affects and verbal responses, while performing upper extremity exercises with both music and karaoke accompaniment music, were observed using video observations."
] |
RAS may be beneficial for gait improvement in people with stroke. These results are encouraging, but more RCTs are needed before recommendations can be made for clinical practice. More research is needed to examine the effects of music therapy on other outcomes in people with ABI.
|
CD003600
|
[
"21464382",
"19114153",
"15173480",
"15805440",
"596497",
"17510847",
"11483803",
"11928967",
"16780288",
"11890582",
"8038252",
"17567977",
"10195971",
"10591231",
"9126518",
"16507741",
"16696748",
"18523108",
"12588572",
"16203842",
"12934722",
"15044414",
"11593439",
"12130606",
"8484447",
"11177061",
"21143436",
"11039967"
] |
[
"A randomized controlled trial of home injury hazard reduction: the HOME injury study.",
"The impact of a home visitation programme on household hazards associated with unintentional childhood injuries: a randomised controlled trial.",
"A randomized, clinical trial of a home safety intervention based in an emergency department setting.",
"Long term effects of a home visit to prevent childhood injury: three year follow up of a randomized trial.",
"Prevention of childhood household injuries: a controlled clinical trial.",
"A randomized trial to assess the effectiveness of an infant home safety programme.",
"The effectiveness of a home visit to prevent childhood injury.",
"Controlled evaluation of a community based injury prevention program in Australia.",
"Evaluating the impact of a child injury prevention project.",
"Preventing falls in older people: outcome evaluation of a randomized controlled trial.",
"Home injuries in children: a population-based intervention trial.",
"Quantifying the effect of a community-based injury prevention program in Queensland using a generalized estimating equation approach.",
"Preventing injuries in children: cluster randomised controlled trial in primary care.",
"Home visits by an occupational therapist for assessment and modification of environmental hazards: a randomized trial of falls prevention.",
"A controlled evaluation of a community injury prevention project in two Greek islands.",
"Efficacy of the North American guidelines for children's agricultural tasks in reducing childhood agricultural injuries.",
"A randomized trial of a multicomponent home intervention to reduce functional difficulties in older adults.",
"Paraprofessional home visitation program to prevent childhood unintentional injuries in low-income communities: a cluster randomized controlled trial.",
"Preventing falls in community-dwelling frail older people using a home intervention team (HIT): results from the randomized Falls-HIT trial.",
"Reaching an underserved population with a randomly assigned home safety intervention.",
"Prevention of farm injuries in Denmark.",
"Impact of social standing on injury prevention in a World Health Organization Safe Community--intervention outcome by household employment contract.",
"Evaluation of an inter-organizational prevention program against injuries among the elderly in a WHO Safe Community.",
"Randomised factorial trial of falls prevention among older people living in their own homes.",
"An injury prevention program in an urban African-American community.",
"Randomized trial of enhanced anticipatory guidance for injury prevention.",
"A randomized controlled trial of a multifactorial falls prevention intervention for older fallers presenting to emergency departments.",
"Effects of a programme of multifactorial home visits on falls and mobility impairments in elderly people at risk: randomised controlled trial."
] |
[
"To test the efficacy of installing safety devices in the homes of young children on total injury rates and on injuries deemed a priori modifiable by the installation of these devices.\n A nested, prospective, randomized controlled trial.\n Indoor environment of housing units.\n Mothers and their children from birth to 3 years old participating in the Home Observation and Measures of the Environment study. Among 8878 prenatal patients, 1263 (14.2%) were eligible, 413 (32.7%) agreed to participate, and 355 were randomly assigned to the intervention (n = 181) or control (n = 174) groups.\n Installation of multiple passive measures (eg, stair gates, cabinet locks, and smoke detectors) to reduce exposure to injury hazards. Injury hazards were assessed at home visits by teams of trained research assistants using a validated survey.\n Modifiable and medically attended injury (ie, telephone calls, office visits, and emergency visits for injury).\n The mean age of children at intervention was 6.3 months. Injury hazards were reduced in the intervention homes but not in the control homes at 1 and 2 years (P < .004). There was no difference in the rate for all medically attended injuries in intervention children compared with controls: 14.3 injuries (95% confidence interval [CI], 9.7-21.1 injuries) vs 20.8 injuries (95% CI, 14.4-29.9 injuries) per 100 child-years (P = .17); but there was a significant reduction in the rate of modifiable medically attended injuries in intervention children compared with controls: 2.3 injuries (95% CI, 1.0-5.5 injuries) vs 7.7 injuries (95% CI, 4.2-14.2 injuries) per 100 child-years (P = .03).\n An intervention to reduce exposure to hazards in homes led to a 70% reduction in the rate of modifiable medically attended injury.\n clinicaltrials.gov Identifier: NCT00129324.",
"The continued high mortality and morbidity rates for unintentional childhood injuries remain a public health concern. This article reports on the influence of a home visitation programme (HVP) on household hazards associated with unintentional childhood injuries in a South African low-income setting.\n A randomised controlled trial (n=211 households) was conducted in a South African informal settlement. Community members were recruited and trained as paraprofessional visitors. Four intervention visits were conducted over 3 months, focusing on child development, and the prevention of burn, poison, and fall injuries. The HVP, a multi-component intervention, included educational inputs, provision of safety devices, and an implicit enforcement strategy. The intervention effect (IE) was measured with a standardised risk assessment index that compared post-intervention scores for intervention and control households.\n A significant reduction was observed in the hazards associated with electrical and paraffin appliances, as well as in hazards related to poisoning. Non-significant changes were observed for burn safety household practices and fall injury hazards.\n This study confirmed that a multi-component HVP effectively reduced household hazards associated with electrical and paraffin appliances and poisoning among children in a low-income South African setting.",
"To assess the effectiveness of an emergency department (ED)-based home safety intervention on caregivers' behaviors and practices related to home safety.\n We conducted a randomized, clinical trial of 96 consecutive caregivers of children who were younger than 5 years and presented to an urban pediatric ED for evaluation of an acute unintentional injury sustained in the home. After completing a structured home safety questionnaire via face-to-face interview, caregivers were randomly assigned to receive either comprehensive home safety education and free safety devices or focused, injury-specific ED discharge instructions. Participants were contacted by telephone 2 months after the initial ED visit for repeat administration of the safety questionnaire. The pretest and posttest questionnaires were scored such that the accrual of points correlated with reporting of safer practices. Scores were then normalized to a 100-point scale. The overall safety score reflected performance on the entire questionnaire, and the 8 category safety scores reflected performance in single areas of home injury prevention (fire, burn, poison, near-drowning, aspiration, cuts/piercings, falls, and safety device use). The main outcome was degree of improvement in safety practices as assessed by improvement in safety scores.\n The intervention group demonstrated a significantly higher average overall safety score at follow-up than the control group (73.3% +/- 8.4% vs 66.8% +/-11.1) and significant improvements in poison, cut/piercing, and burns category scores. Caregivers in the intervention group also demonstrated greater improvement in reported use of the distributed safety devices.\n This educational and device disbursement intervention was effective in improving the home safety practices of caregivers of young children. Moreover, the ED was used effectively to disseminate home injury prevention information.",
"To assess the long term effect of a home safety visit on the rate of home injury.\n Telephone survey conducted 36 months after participation in a randomized controlled trial of a home safety intervention. A structured interview assessed participant knowledge, beliefs, or practices around injury prevention and the number of injuries requiring medical attention.\n Five pediatric teaching hospitals in four Canadian urban centres.\n Children less than 8 years of age presenting to an emergency department with a targeted home injury (fall, scald, burn, poisoning or ingestion, choking, or head injury while riding a bicycle), a non-targeted injury, or a medical illness.\n We contacted 774 (66%) of the 1172 original participants. A higher proportion of participants in the intervention group (63%) reported that home visits changed their knowledge, beliefs, or practices around the prevention of home injuries compared with those in the non-intervention group (43%; p<0.001). Over the 36 month follow up period the rate of injury visits to the doctor was significantly less for the intervention group (rate ratio = 0.74; 95% CI 0.63 to 0.87), consistent with the original (12 month) study results (rate ratio = 0.69; 95% CI 0.54 to 0.88). However, the effectiveness of the intervention appears to be diminishing with time (rate ratio for the 12-36 month study interval = 0.80; 95% CI 0.64 to 1.00).\n A home safety visit was able to demonstrate sustained, but modest, effectiveness of an intervention aimed at improving home safety and reducing injury. This study reinforces the need of home safety programs to focus on passive intervention and a simple well defined message.",
"Injuries claim the lives of more children each year than the next six leading pediatric disorders combined, and produce injuries that require medical attention for one in three children. In the preschool age group, 91 per cent of these accidents and over one-half the resultant fatalities occur in the home. This paper reports the results of a controlled clinical trial conducted to evaluate the implementation of a health education program intended to reduce the risk of childhood household injuries. The study population was randomly assigned into two demographically comparable groups. Only the experimental group mothers received an educational intervention consisting of a tutorial, home safety-proofing assignments, and follow-up. The homes of the two groups were later assessed for hazards during an unannounced visit by an interviewer who did not know to which group each home belonged. A home safety score mean for the two groups was almost identical. The program stimulated heightened interest and stated intent to improve, but did not result in actual reduction of household hazards. Active health education, as used and evaluated in this study, appears to have limited effectiveness when applied to home safety. Approaches such as \"passive\" measures may offer greater potential for household injury reduction.",
"The aim of this study was to test an intervention aimed at addressing the risk of injury in infants 2 - 12 months of age. A non-blinded, randomized controlled trial was conducted, whereby parents were randomly assigned to either a control or one of two intervention groups. Parents completed questionnaires regarding safety behaviours and injuries at the 2 (baseline), 6 and 12 month immunization visit at the community health unit. During the 2 month visit to the health unit, the two intervention groups received a home safety kit containing nine items, an instructional brochure and a risk assessment checklist. Subjects randomized to the safety kit plus home visit group also received a standardized home visit from a community health nurse. Two of the 14 parental safety behaviours showed a significant increase in use among parents in the intervention groups. Neither of the interventions was associated with a reduction in parent-reported injuries among children. It was concluded that home visitation may provide a beneficial adjunct to the provision of safety devices and may increase use by parents.",
"To examine the effectiveness of a home visit program to improve home safety and decrease the frequency of injury in children. We examined the effects of the program on 1) parental injury awareness and knowledge; 2) the extent that families used home safety measures; 3) the rate of injury; and 4) the cost effectiveness of the intervention.\n A randomized, controlled trial.\n A multicenter trial conducted at 5 hospitals in 4 Canadian urban centers.\n Children <8 years old, initially enrolled in an injury case-control study, were eligible to participate. Intervention. Subsequent to a home inspection conducted to determine baseline hazard rates for both groups, participants in the intervention group received a single home visit that included the provision of an information package, discount coupons, and specific instruction regarding home safety measures. Main\n The median age was 2 years, with males comprising ~60% of participants. The experimental groups were comparable at outset in terms of case-control status, age, gender, and socioeconomic status. Parental injury awareness and knowledge was high; 73% correctly identified injury as the leading cause of death in children, and an intervention effect was not demonstrated. The adjusted odds ratios (ORs) for the home inspection items indicated that significant safety modifications only occurred in the number of homes having hot water not exceeding 54 degrees C (OR: 1.31, 95% confidence interval [CI]: 1.14, 1.50) or the presence of a smoke detector (OR: 1.45, 95% CI: 0.94, 2.22). However, the intervention group reported home safety modifications of 62% at 4 months and significantly less injury visits to the doctor compared with the nonintervention group (rate ratio: 0.75; 95% CI: 0.58, 0.96). The total costs of care for injuries were significantly lower in the intervention group compared with the nonintervention group with a cost of $372 per injury prevented.\n An intervention using a single home visit to improve the extent to which families use safety measures was found to be insufficient to influence the long-term adoption of home safety measures, but was effective to decrease the overall occurrence of injuries. Future programs should target a few, well-focused, evidence-based areas including the evaluation of high-risk groups and the effect of repeated visits on outcome.",
"To evaluate the effects of a community based, all age, all injury prevention program, the Safe Living Program, on injury risk and injury rates.\n A quasiexperimental population based evaluation using an intervention and comparison community design.\n The intervention community (Shire of Bulla, n = 37,257) is an outer metropolitan area of Melbourne, Australia. The demographically matched comparison community (Shire of Melton, n=33,592) is located nearby.\n The Safe Living Program in the Shire of Bulla targeted injury reduction in all settings with a focus on high risk groups. Strategies included program publicity, education and training, injury hazard reduction, and environmental change. Baseline and follow up measures of program reach, risk factors, and injury rates in both communities were used to evaluate program process, impact, and outcome.\n Increase in program awareness was moderate and similar to other community based programs. The program achieved injury hazard reduction on the road, in schools, and, to a more limited extent, in the home. Other changes in injury risk factors could not necessarily be attributed to the program as similar changes were observed in the comparison community. No significant changes were found in rates of injury deaths, hospitalisations, or emergency department presentations in the Shire of Bulla after six years. Self reported household injuries, mostly minor, were reduced in the intervention community, but had been higher at program launch than in the comparison community.\n The Safe Living Program was unable to replicate the significant reductions in injuries reported in other community based interventions. Replication of apparently successful community based injury prevention programs in different settings and populations requires evidence based interventions, sustained and effective program penetration, reliable data systems to measure change, at least one control community, and sufficient budget and time for effects to be observable.",
"This article describes an evaluation study which assessed the effectiveness of a child injury prevention project in deprived localities. The initiative took place across the Bumley, Pendle and Rossendale Primary Care Trust locality in East Lancashire. Families with children under five years of age living within this locality participated in the study. The intervention consisted of a home safety consultation and the provision and fitting of low-cost safety equipment to 1234 families and their homes within Sure Start programme areas that chose to access the Home Safety Equipment Scheme. In addition to this targeted work in these programme areas, a population-wide education and information campaign was provided across the whole locality. Rates of attendance at an accident and emergency (A&E) department by children aged less than five years of age following an injury were used to assess the outcome of the intervention. Results showed that over two years the proportion of children attending an A&E department reduced at a faster rate in the intervention than in the non-intervention wards, thereby reducing the health inequalities gap. It was therefore concluded that targeted work with parents of young children living in disadvantaged areas, together with the provision and fitting of low-cost safety equipment, can improve health and reduce inequalities among the local under-five population.",
"To evaluate the outcome of an intervention to reduce hazards in the home on the rate of falls in seniors.\n Randomized controlled trial, with follow-up of subjects for 1 year.\n Community-based study in Perth, Western Australia.\n People age 70 and older.\n One thousand eight hundred seventy-nine subjects were recruited and randomly allocated by household to the intervention and control groups in the ratio 1:2. Because of early withdrawals, 1,737 subjects commenced the study. All members of both groups received a single home visit from a research nurse. Intervention subjects (n = 570) were offered a home hazard assessment, information on hazard reduction, and the installation of safety devices, whereas control subjects (n = 1,167) received no safety devices or information on home hazard reduction.\n Both groups recorded falls on a daily calendar. Reported falls were confirmed by a semistructured telephone interview and were assigned to one of three overlapping categories: all falls, falls inside the home, and falls involving environmental hazards in the home. Analysis was by multivariate modelling of rate ratios and odds ratios for falls, corrected for household clustering, using Poisson regression and logistic regression with robust variance estimation.\n Overall, 86% of study subjects completed the 1 year of follow-up. The intervention was not associated with any significant reduction in falls or fall-related injuries. There was no significant reduction in the intervention group in the incidence rate of falls involving environmental hazards inside the home (adjusted rate ratio, 1.11; 95% CI = 0.82-1.50), or the proportion of the intervention group who fell because of hazards inside the home (adjusted odds ratio, 0.97; 95% CI = 0.74-1.28). No reduction was seen in the rate of all falls (adjusted rate ratio, 1.02; 95% CI = 0.83-1.27) or the rate of falls inside the home (adjusted rate ratio, 1.17; 95% CI = 0.85-1.60). There was no significant reduction in the rate of injurious falls in intervention subjects (adjusted rate ratio, 0.92; 95% CI = 0.73-1.14).\n The intervention failed to achieve a reduction in the occurrence of falls. This was most likely because the intervention strategies had a limited effect on the number of hazards in the homes of intervention subjects. The study provides evidence that a one-time intervention program of education, hazard assessment, and home modification to reduce fall hazards in the homes of healthy older people is not an effective strategy for the prevention of falls in seniors.",
"We conducted a population-based intervention trial to evaluate the effectiveness of a program to prevent home injuries in children. We recruited a population of 1,015 young parent couples. Among those couples, we measured attitudes toward prevention of home injuries to children before and after the intervention. The intervention had limited effectiveness, which was somewhat greater among white-collar families and families with a higher paternal educational level. We found an association between the occurrence of injuries and educational level of the fathers (odds ratio = 1.7 and 1.9 for 6-12 years and < 6 years of school completed, respectively, vs > or = 13 years).",
"To develop a generalized estimating equation (GEE) model of childhood injury rates to quantify the effectiveness of a community-based injury prevention program implemented in 2 communities in Australia, in order to contribute to the discussion of community-based injury prevention program evaluation.\n An ecological study was conducted comparing injury rates in two intervention communities in rural and remote Queensland, Australia, with those of 16 control regions. A model of childhood injury was built using hospitalization injury rate data from 1 July 1991 to 30 June 2005 and 16 social variables. The model was built using GEE analysis and was used to estimate parameters and to test the effectiveness of the intervention.\n When social variables were controlled for, the intervention was associated with a decrease of 0.09 injuries/10,000 children aged 0-4 years (95% CI -0.29 to 0.11) in logarithmically transformed injury rates; however, this decrease was not significant (p = 0.36).\n The evaluation methods proposed in this study provide a way of determining the effectiveness of a community-based injury prevention program while considering the effect of baseline differences and secular changes in social variables.",
"To assess the effectiveness of safety advice at child health surveillance consultations, provision of low cost safety equipment to families receiving means tested state benefits, home safety checks, and first aid training on frequency and severity of unintentional injuries in children at home.\n Cluster randomised controlled trial.\n 36 general practices in Nottingham.\n All children aged 3-12 months registered with participating practices.\n A package of safety advice at child health surveillance consultations at 6-9, 12-15, and 18-24 months; provision of low cost safety equipment to families on means tested state benefits; and home safety checks and first aid training by health visitors.\n Primary outcomes measures were frequency and severity of medically attended injuries. Secondary outcome measures were self reported safety practices, possession and use of safety equipment, knowledge and confidence in dealing with first aid, and perceptions of risk of injury and risk of hazards assessed by postal questionnaire at baseline and follow up at 25 months.\n At baseline, both groups had similar risk factors for injury, sociodemographic characteristics, safety practices, possession and use of safety equipment, knowledge and confidence in dealing with first aid, and perceptions of risk. No significant difference was found in frequency of at least one medically attended injury (odds ratio 0.97, 95% confidence interval 0.72 to 1.30), at least one attendance at an accident and emergency department for injury (1.02, 0.76 to 1.37), at least one primary care attendance for injury (0.75, 0.48 to 1.17), or at least one hospital admission for injury (0.69, 0.42 to 1.12). No significant difference in the secondary outcome measures was found between the intervention and control groups.\n The intervention package was not effective in reducing the frequency of minor unintentional injuries in children at home, and larger trials are required to assess the effect on more severe injuries.",
"To determine whether occupational therapist home visits targeted at environmental hazards reduce the risk of falls.\n A randomized controlled trial.\n Private dwellings in the community in Sydney, Australia.\n A total of 530 subjects (mean age 77 years), recruited primarily before discharge from selected hospital wards.\n A home visit by an experienced occupational therapist, who assessed the home for environmental hazards and facilitated any necessary home modifications.\n The primary study outcome was falls, ascertained over a 12-month follow-up period using a monthly falls calendar.\n Thirty six percent of subjects in the intervention group had at least one fall during follow-up, compared with 45% of controls (P = .050). The intervention was effective only among subjects (n = 206) who reported having had one or more falls during the year before recruitment into the study; in this group, the relative risk of at least one fall during follow-up was 0.64 (95% confidence interval, 0.50-0.83). Similar results were obtained when falls data were analyzed using survival analysis techniques (proportional and multiplicative hazards models) and fall rates (mean number of falls per person per year). About 50% of the recommended home modifications were in place at a 12-month follow-up visit.\n Home visits by occupational therapists can prevent falls among older people who are at increased risk of falling. However, the effect may not be caused by home modifications alone. Home visits by occupational therapists may also lead to changes in behavior that enable older people to live more safely in both the home and the external environment.",
"During the 20-month period September 1993 to April 1995, a health education injury prevention programme focusing on home injuries among the young (< or = 18 years old) and elderly (> or = 65 years old) on the Greek island of Naxos was undertaken, its effectiveness was evaluated by comparing the subsequent injury experience in sentinel population groups in Naxos as well as in Spetses, another island of similar sociodemographic profile, where no such intervention programme had been formally implemented.\n On the island-of Naxos an injury prevention campaign was initially undertaken involving virtually all opinion leaders and implemented through lectures, workshops and publicity in the local media. The main intervention focused on 172 households on the island of Naxos and was done by trained local collaborators who visited each household weekly to provide injury prevention advice and assess home safety. Similar visits were done by untrained collaborators in 177 households on the island of Spetses in order to assure collaboration of household members in the comparative evaluation stage of the programme. The process evaluation was based on ascertained changes of safety features and attitudes in the participating households, whereas the outcome evaluation was based on the incidence of injuries among members of the participating households in the two islands over a period of 8.5 months (255 days).\n On the intervention island of Naxos there were statistically significant improvements with respect to 11 of the 28 examined variables, whereas on the island of Spetses, such improvement was only noted for one variable. The age-adjusted incidence rate ratio of injuries overall among the target groups, contrasting the intervention and the control households was 0.85 with 90% confidence interval (CI): 0.69-1.05. With respect to home accidents the corresponding ratio was 0.79 with 90% CI: 0.60-1.04.\n An intensive and focused injury prevention intervention had only modest success when injuries themselves were the outcome variable.",
"We assessed whether active dissemination of the North American Guidelines for Children's Agricultural Tasks (NAGCAT) reduced childhood agricultural injuries.\n In this randomized controlled trial, lay educators visited intervention farms to review NAGCAT. New York State farms with resident or working children were randomized. Control farms were visited only to collect baseline data. Data on childhood injuries, tasks, and hours worked were obtained quarterly for 21 months. Injury rates per farm were compared between the treatment and control groups, along with time span to occurrence of an injury and to violation of NAGCAT age guidelines.\n Intervention farms were less likely than control farms to violate NAGCAT age guidelines in the areas of all-terrain-vehicle use and tractor and haying operations. Cox proportional hazards regression models showed a significant protective effect of the intervention on preventable injuries after adjustment for important covariates.\n Our results showed that dissemination of NAGCAT reduced rates of work-related childhood agricultural injuries. A comprehensive public health approach is needed to reduce non-work-related childhood injuries.",
"To test the efficacy of a multicomponent intervention to reduce functional difficulties, fear of falling, and home hazards and enhance self-efficacy and adaptive coping in older adults with chronic conditions.\n A prospective, two-group, randomized trial. Participants were randomized to a treatment group or no-treatment group.\n Urban community-living older people.\n Three hundred nineteen community-living adults aged 70 and older who reported difficulty with one or more activities of daily living.\n Occupational and physical therapy sessions involving home modifications and training in their use; instruction in strategies of problem-solving, energy conservation, safe performance, and fall recovery techniques; and balance and muscle strength training.\n Outcome measures included self-rated functional difficulties with ambulation, instrumental activities of daily living, activities of daily living, fear of falling, confidence performing daily tasks, and use of adaptive strategies. Observations of home hazards were also conducted.\n At 6 months, intervention participants had less difficulty than controls with instrumental activities of daily living (P=.04, 95% confidence interval (CI)=-0.28-0.00) and activities of daily living (P=.03, 95% CI=-0.24 to -0.01), with largest reductions in bathing (P=.02, 95% CI=-0.52 to -0.06) and toileting (P=.049, 95% CI=-0.35-0.00). They also had greater self-efficacy (P=.03, 95% CI=0.02-0.27), less fear of falling (P=.001, 95% CI=0.26-0.96), fewer home hazards (P=.05, 95% CI=-3.06-0.00), and greater use of adaptive strategies (P=.009, 95% CI=0.03-0.22). Benefits were sustained at 12 months for most outcomes.\n A multicomponent intervention targeting modifiable environmental and behavioral factors results in life quality improvements in community-dwelling older people who had functional difficulties, with most benefits retained over a year.",
"To investigate the effectiveness of a paraprofessional home visitation program (HVP) to improve home safety and prevent injuries among children living in low-income settings.\n The HVP was implemented in two low-income communities in South Africa. In each community, approximately 200 households were randomly selected for the trial. Eligible households were those with children aged < or = 10 years. Intervention households received four visits, one every two weeks, by trained paraprofessionals that focused on a specific injury topic and consisted of: information dissemination about specific injury prevention practices; home inspection accompanied by information about home hazards; and the supply of safety devices. The key outcomes to measure the presence of home hazards were scores for burns (safety practices, paraffin, and electrical), poisoning, and falls.\n Significant reductions were found for injury risks related to burn safety practices. For injury risks related to electrical burns, paraffin burns, and poisoning, a decline was also noted although this was not statistically significant. No decline was noted for fall-related risks.\n Subject to further replication and evaluation, home visits by paraprofessionals providing safety education, home inspection, and safety devices be considered for integration into a comprehensive child injury prevention strategy in low-income communities.",
"To evaluate the effect of an intervention by a multidisciplinary team to reduce falls in older people's homes.\n Randomized, controlled trial with follow-up of subjects for 1 year.\n University-affiliated geriatric hospital and older patients' homes.\n Three hundred sixty subjects (mean age +/- standard deviation = 81.5 +/- 6.4) admitted from home to a geriatric hospital and showing functional decline, especially in mobility.\n The participants were randomly assigned to receive a comprehensive geriatric assessment followed by a diagnostic home visit and home intervention or a comprehensive geriatric assessment with recommendations and usual care at home. The home intervention included a diagnostic home visit, assessing the home for environmental hazards, advice about possible changes, offer of facilities for any necessary home modifications, and training in the use of technical and mobility aids. An additional home visit was made after 3 months to reinforce the recommendations. After 12 months of follow-up, a home visit was made to all study participants.\n Number of falls, type of recommended home modifications, and compliance with recommendations.\n After 1 year, there were 163 falls in the intervention group and 204 falls in the control group. The intervention group had 31% fewer falls than the control group (incidence rate ratio (IRR) = 0.69, 95% confidence interval (CI) = 0.51-0.97). The intervention was most effective in a subgroup of participants who reported having had two or more falls during the year before recruitment into the study. In this subgroup, the proportion of frequent fallers and the rate of falls was significantly reduced for the intervention group compared with the control group (21 vs 36 subjects with recurrent falls, P =.009; IRR = 0.63, 95% CI = 0.43-0.94). The compliance rate varied with the type of change recommended from 83% to 33% after 12 months of follow-up.\n Home intervention based on home visits to assess the home for environmental hazards, providing information about possible changes, facilitating any necessary modifications, and training in the use of technical and mobility aids was effective in a selected group of frail older subjects with a history of recurrent falling.",
"To access an underserved, mobile segment of a monolingual Spanish speaking population and to improve maternal self efficacy for home safety behaviors using a culturally appropriate intervention.\n A pre- and post-test experimental design tested differences in maternal childhood injury health beliefs (MCIHB) and controllable safety hazards (CHS). Participants were randomly assigned to experimental and control groups. Baseline data assessed demographic and study variables comparability. The intervention included counseling, assessment of maternal safety practices, and provision of safety items.\n A non-urban area in Texas where low income, largely migrant Hispanics represent the majority of residents.\n Eighty two mothers of 1--4 year old children.\n The 95% retention rate of an itinerant, hard to reach population suggests that minority participants may be receptive to culturally appropriate home visits. The intervention group demonstrated improved self efficacy for home safety behaviors (F (2, 77)=7.50, p=0.01). Mothers with stronger self efficacy and fewer perceived barriers had fewer accessible in-home hazards. Observed home hazard predictors were: (a) never being married; (b) poor home repair, (c) lower self efficacy for safety behaviors; and (d) control group status.\n Safety items coupled with a home visit tailored to child age and maternal culture was an effective intervention in a hard to reach population. This study contributes to designing research for a monolingual population with limited local language proficiency and community residency. Injuries represent a major source of health disparities in these neglected populations.",
"This study examined the effects of a 4-year randomized intervention program that combined a safety audit with safety behavior training in the prevention of farm injuries.\n From a random sample of farms in the county of Ringkoebing, Denmark, 393 farms with 1597 residents and employees participated in a weekly self-registration of work-related accidents and injuries during 1 year. Worktasks and time at risk were recorded. A questionnaire including items on safety behavior was also mailed to each farm. Thereafter, the farms were randomly assigned to an intervention or control group. Two hundred and one farms with 990 persons at risk participated in the intervention study. The main outcome measures were the number and severity of accidents, safety behavior, and farmsite safety audits.\n Pre- and postmeasurements showed a substantial reduction in injury rates in the intervention group in comparison with a slight reduction in the control group. In a multivariate regression analysis the intervention effect was estimated to be a 30% injury-rate reduction of all injuries, while there was a 42% reduction for medically treated injuries only. Although none of these effects are statistically significant with the present sample size, their magnitude and direction support an intervention effect. The measures of safety behavior revealed significant improvements, and this finding supports the conclusion that the intervention effect was positive, since they concern some of the mediating factors on the pathway from intervention to improved injury rates.\n This intervention, which focused on safety behavior and was performed as a randomized controlled trial, was followed by a substantial reduction in the number of farm injuries. The reduction was particularly marked for the more severe injuries demanding medical treatment.",
"Although social inequality in health has been an argument for community-based injury prevention programmes, intervention outcomes with regard to differences in social standing have not been analysed. The objective of this study was to investigate rates of injuries treated in health-care among members of households at different levels of labour market integration before and after the implementation of a WHO Safe Community programme.\n A quasi-experimental design was used with pre- and post-implementation data collection covering the total populations <65 years of age during one year in the programme implementation municipality (population 41 000) and in a control municipality (population 26 000). Changes in injury rates were studied using prospective registration of all acute care episodes with regard to social standing in both areas during the study periods.\n Male members of households categorized as not vocationally active displayed the highest pre-intervention injury rates. Also after the intervention, males in households classified as not vocationally active displayed notably elevated injury rates in both the control and study areas. Households in the study area in which the significant member was employed showed a post-intervention decrease in injury rate among both men (P < 0.001) and women (P < 0.01). No statistically significant change was observed in households in which the significant member was self-employed or not vocationally active. In the control area, only an aggregate-level decrease (P < 0.05) among members of households in which the significant member was employed was observed.\n The study displayed areas for improvement in the civic network-based WHO Safe Community model. Even though members of non-vocationally active households, in particular men, were at higher pre-intervention injury risk, they were not affected by the interventions. This fact has to be addressed when planning future community-based injury prevention programmes.",
"The aim of the study was to evaluate the outcome of a participatory community-based prevention program against injuries among the elderly. A population-based quasi-experimental design was used with pre- and post-implementation measurements in an intervention and a control area. The program was based on cross-sectoral participation in detecting and taking action against injuries among the elderly. Change in the relative risk of injury was estimated by the odds ratio. Morbidity in moderately (AIS 2) severe injury in the study area was reduced from 46 per 1000 population years to 25 per 1000 population years (odds ratio 0.55; 95% confidence interval 0.46-0.65), while the minor (AIS 1) injuries increased (odds ratio 1.55; 95% confidence interval 1.21-1.91). The risk of severe or fatal (AIS 3-6) injuries remained constant. In the study area, only a slight decrease in the total morbidity rate was observed (odds ratio 0.87; 95% confidence interval 0.77-0.99). In the control area, there was no evident change in the total morbidity rates. Falls decreased or showed a tendency to decrease in the age groups 65 to 79-y-old in the study area, while they increased in the older age group. The results indicate that no sharp boundaries should be drawn between safety education, physical conditioning, environmental adjustments and secondary prevention measures when planning safety promotion among the elderly. Future studies should address these issues along with the methodological complexity associated with assessment of participatory community-based safety promotion programs.",
"To test the effectiveness of, and explore interactions between, three interventions to prevent falls among older people.\n A randomised controlled trial with a full factorial design.\n Urban community in Melbourne, Australia.\n 1090 aged 70 years and over and living at home. Most were Australian born and rated their health as good to excellent; just over half lived alone.\n Three interventions (group based exercise, home hazard management, and vision improvement) delivered to eight groups defined by the presence or absence of each intervention.\n Time to first fall ascertained by an 18 month falls calendar and analysed with survival analysis techniques. Changes to targeted risk factors were assessed by using measures of quadriceps strength, balance, vision, and number of hazards in the home.\n The rate ratio for exercise was 0.82 (95% confidence interval 0.70 to 0.97, P=0.02), and a significant effect (P<0.05) was observed for the combinations of interventions that involved exercise. Balance measures improved significantly among the exercise group. Neither home hazard management nor treatment of poor vision showed a significant effect. The strongest effect was observed for all three interventions combined (rate ratio 0.67 (0.51 to 0.88, P=0.004)), producing an estimated 14.0% reduction in the annual fall rate. The number of people needed to be treated to prevent one fall a year ranged from 32 for home hazard management to 7 for all three interventions combined.\n Group based exercise was the most potent single intervention tested, and the reduction in falls among this group seems to have been associated with improved balance. Falls were further reduced by the addition of home hazard management or reduced vision management, or both of these. Cost effectiveness is yet to be examined. These findings are most applicable to Australian born adults aged 70-84 years living at home who rate their health as good.",
"Injury is a major US public health problem, particularly in urban minority communities. This paper evaluates the impact of the Safe Block Project, a comprehensive injury prevention trial, on home hazards and injury prevention knowledge in a poor urban African-American community.\n Nine census tracts in the community were allocated to either the intervention area or the control area. The intervention, carried out by trained community outreach workers, consisted of (1) home modification for simple prevention measures, (2) home inspection accompanied by information about home hazards, and (3) education about selected injury prevention practices. Approximately 12 months after the intervention, random samples of control and intervention homes were assessed for home hazards and injury prevention knowledge.\n A significantly larger proportion of intervention homes than control homes had functioning smoke detectors, syrup of ipecac, safely stored medications, and reduced electrical and tripping hazards. No consistent differences were observed between control and intervention homes on home hazards requiring major effort to correct.\n There was a distinct difference between control and intervention homes with respect to safety knowledge and home hazards requiring minimal to moderate effort to correct. The Safe Block Project could serve as a model for future urban injury prevention efforts.",
"To develop and evaluate an injury prevention anticipatory guidance training program for pediatric residents.\n Thirty-one residents were randomly assigned to an intervention or control group. Both groups attended a 1-hour seminar about injury prevention and the American Academy of Pediatrics TIPP (The Injury Prevention Program) materials. The intervention group also received 5 hours of experiential instruction on injury prevention content and counseling skills (SAFE Counseling Framework). Families with infants from birth to age 6 months were enrolled in the study (N = 196); they were followed up until the child was aged 12 to 18 months. Data were collected by means of baseline and follow-up interviews, audiotapes of medical visits, parent exit surveys, and home observations.\n A hospital-based continuity clinic that serves families living in low-income, inner-city neighborhoods.\n Physician counseling and parent satisfaction, knowledge, beliefs, and behaviors.\n Parents seen by physicians in the intervention group received significantly more injury prevention counseling for 5 of the 6 safety practices, and they were significantly more satisfied with the help their physicians provided on safety topics. They were no less satisfied with their physicians' counseling on other anticipatory guidance topics. Parents' knowledge, beliefs, and home safety behaviors did not differ between the 2 groups.\n The frequency and impact of pediatric counseling can be enhanced by experiential training that targets specific injury hazards. Because low-income families face many barriers to carrying out the recommended safety practices, supplemental strategies are needed to ensure safer homes.",
"To investigate the effect of a referral-based targeted multifactorial falls prevention intervention on the occurrence of recurrent falls and injuries in older people presenting to an emergency department (ED) after a fall and discharged directly home from the ED.\n Randomized controlled trial. Assessors of outcomes were unaware of group allocation.\n Seven EDs in metropolitan Melbourne, Australia.\n Inclusion criteria were community dwelling, aged 60 and older, presenting to an ED after a fall, and discharged directly home. Exclusion criteria were unable to follow simple instructions or walk independently.\n Targeted referrals to existing community services and health promotion recommendations, based on the falls risk factors found in a baseline assessment.\n Primary outcome measures were falls and resultant injuries occurring over the 12-month follow-up period. Falls and injury data were collected using falls calendars supported by medical record reviews.\n Three hundred sixty-one participants were randomized to the standard care group and 351 to the intervention group. No significant difference was found between the two groups over the 12-month follow-up period in number of fallers (relative risk (RR)=1.11, 95% confidence interval (CI)=0.95-1.31] or number of participants sustaining an injury from a fall (RR=1.06, 95% CI=0.86-1.29).\n This study does not support the use of a referral-based targeted multifactorial intervention program to reduce subsequent falls or fall injuries in older people who present to an ED after a fall.\n © 2010, Copyright the Authors. Journal compilation © 2010, The American Geriatrics Society.",
"To evaluate whether a programme of multifactorial home visits reduces falls and impairments in mobility in elderly people living in the community.\n Randomised controlled trial with 18 months of follow up.\n Six general practices in Hoensbroek, the Netherlands.\n 316 people aged 70 and over living in the community, with moderate impairments in mobility or a history of recent falls.\n Five home visits by a community nurse over a period of one year. Visits consisted of screening for medical, environmental, and behavioural factors causing falls and impairments in mobility, followed by specific advice, referrals, and other actions aimed at dealing with the observed hazards.\n Falls and impairments in mobility.\n No differences were found in falls and mobility outcomes between the intervention and usual care groups.\n Multifactorial home visits had no effects on falls and impairments in mobility in elderly people at risk who were living in the community. Because falls and impairments in mobility remain a serious problem among elderly people, alternative strategies should be developed and evaluated."
] |
There is insufficient evidence to determine whether interventions focused on modifying environmental home hazards reduce injuries. Further interventions to reduce hazards in the home should be evaluated by adequately designed randomised controlled trials measuring injury outcomes. Recruitment of large study samples to measure effect must be a major consideration for future trials. Researchers should also consider using factorial designs to allow the evaluation of individual components of multifactorial interventions.
|
CD000103
|
[
"2885946",
"17126719",
"6209832",
"8073455",
"1699308",
"2880214",
"12097849",
"2466351",
"1561645",
"10815082",
"18212034",
"12511758"
] |
[
"Multicenter trial of hemodilution in acute ischemic stroke. I. Results in the total patient population. Scandinavian Stroke Study Group.",
"Intravenous ancrod for acute ischaemic stroke in the European Stroke Treatment with Ancrod Trial: a randomised controlled trial.",
"A randomized controlled trial of hemodilution therapy in acute ischemic stroke.",
"Ancrod for the treatment of acute ischemic brain infarction. The Ancrod Stroke Study Investigators.",
"Adjusted hypervolemic hemodilution in acute ischemic stroke.",
"Double-blind randomised trial of intravenous glycerol in acute stroke.",
"Hydroxyethyl starch for hypervolemic hemodilution in patients with acute ischemic stroke: a randomized, placebo-controlled phase II safety study.",
"Hypervolemic hemodilution treatment of acute stroke. Results of a randomized multicenter trial using pentastarch. The Hemodilution in Stroke Study Group.",
"Custom-tailored hemodilution with albumin and crystalloids in acute ischemic stroke.",
"Intravenous ancrod for treatment of acute ischemic stroke: the STAT study: a randomized controlled trial. Stroke Treatment with Ancrod Trial.",
"A pilot randomized controlled trial to evaluate the benefit of the cardiac rehabilitation paradigm for the non-acute ischaemic stroke population.",
"Admitting acute ischemic stroke patients to a stroke care monitoring unit versus a conventional stroke unit: a randomized pilot study."
] |
[
"Hemodilution by the combination of venesection and dextran 40 administration has previously been reported to enhance neurologic recovery in the acute phase of ischemic stroke. To study this therapeutic principle in its \"natural habitat,\" a stratified and randomized multicenter trial involving 15 large and small hospitals was performed. Patients with acute ischemic stroke of less than 48 hours' duration and with hematocrits of 38-50% on admission were randomized to a hemodilution (183 patients, mean age 72.0 years) or a control group (190 patients, mean age 71.6 years). The two groups did not differ in sex distribution or medical history. Hematocrit, blood pressure, and neurologic score were closely similar at entry. By graded venesection (250-1000 ml) during the first 2 days and dextran 40 infusions (500 ml daily) during 5 days, the mean hematocrit was reduced from 44.2 to 37.1%. Three-month survival expressed as life table product was 0.84 in hemodilution and 0.88 in control patients. In survivors, neurologic score and activities of daily living performance during 3 months of follow-up were not improved by hemodilution. Length of stay in an acute-care hospital and the need for long-term institutional care was not reduced among patients in the hemodilution group. Major cardiovascular events occurred somewhat more often and there was an apparent increase in mortality during the first few days of hemodilution therapy. However, the differences were not significant. We conclude that the present standardized treatment with moderate hemodilution has no overall beneficial effects in general patients with acute ischemic stroke.",
"Intravenous tissue plasminogen activator is the only approved specific treatment for acute ischaemic stroke. Ancrod, a natural defibrinogenating agent from snake venom, has proved to have a favourable effect when given within 3 h after an acute ischaemic stroke. The European Stroke Treatment with Ancrod Trial was undertaken to assess the effects of ancrod when given within 6 h.\n 1222 patients with an acute ischaemic stroke were included in this randomised double-blind placebo-controlled trial. Brain CT scans were done to exclude intracranial haemorrhages and large evolving ischaemic infarctions. Patients were randomly assigned ancrod (n=604) or placebo (n=618). The primary outcome was functional success at 3 months (survival, Barthel Index of 95 or 100, or return to prestroke level). The analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, trial number NCT00343174.\n Functional success at 3 months did not differ between patients given ancrod (42%) and those given placebo (42%) (p=0.94, OR=0.99, 95% CI, 0.76-1.29).\n On the basis of our findings, ancrod should not be recommended for use in acute ischaemic stroke beyond 3 h.",
"Rapid hemodilution in the early phase of ischemic stroke by the combination of venesection (250-650 ml during the first 2 days) and administration of low-molecular weight dextran was evaluated in a prospective controlled trial. Fifty-two patients were randomized to hemodilution therapy and 50 to a control group; the two groups were comparable in important prognostic variables. Mean hemoglobin was reduced from 147 to 127 g/l, hematocrit from 43 to 37% and, in a subsample of patients, whole-blood viscosity at a shear rate of 23 sec-1 from 7.0 to 4.3 cps over the first 2 days. Hemodilution was then maintained by repeated dextran infusions. Of the hemodiluted patients, 85% improved in neurological scoring over the first 10 days as compared to 64% of the control patients (p less than 0.025). The case fatality rate during the first 3 months was little affected by hemodilution. Among the survivors, 8% of the hemodiluted and 31% of the non-hemodiluted patients were unable to walk at 3 months. The proportion of surviving patients still hospitalized at the 3-month follow-up was 13% in the hemodilution group and 39% in the control group (p less than 0.01). The combination of venesection and dextran 40 administration is thus an unsophisticated but effective way to achieve rapid hemodilution in patients with acute cerebral infarction, and it improves the overall clinical outcome over the first 3 months.",
"There is no acute therapy proven to be of benefit for ischemic stroke. Ancrod is a potentially effective therapy because of the advantageous consequences of fibrinogen lowering.\n We studied the safety and efficacy of ancrod in patients with acute ischemic stroke administered within 6 hours of stroke onset. In a double-blind, randomized, placebo-controlled trial 64 patients received intravenous ancrod and 68 received placebo for 7 days. Neurological outcome, disability, and brain infarct volume were measured.\n There was no significant difference in overall mean scores on the Scandinavian Stroke Scale. No increase in bleeding occurred in the ancrod-treated patients. The target reduction of plasma fibrinogen levels of less than 100 mg/dL was achieved in only 15 (23%) of 64 ancrod-treated patients. Those patients with ancrod-induced 6-hour fibrinogen levels 130 mg/dL or less had a marginally significantly better neurological outcome on the Scandinavian Stroke Scale, mortality, and Barthel Index than ancrod-treated patients with higher fibrinogen levels.\n Ancrod appears safe and potentially effective when administered to patients within 6 hours of onset of ischemic stroke.",
"We prospectively randomized 47 patients with acute ischemic stroke of the middle cerebral artery of less than 24 hours' duration to either adjusted hypervolemic hemodilution or control treatment and followed them up for 90 days. Rapid hemodilution to a target hematocrit of 30-35% as monitored with bedside determinations was achieved by using infusions of dextran 40, venesections, and infusions of additional crystalloid solution when necessary. There was no difference in the death rate between the two treatment groups. Of these 47 patients, 37 (19 in the hemodilution group and 18 in the control group) could be followed up for the entire study period of 3 months. The relative improvement in neurologic function from day 1 to days 8, 21, and 90 was significantly better in the hemodilution group than in the control group. In accordance, special tests for fine motor control of the paretic arm disclosed better performance in the hemodilution group. The frequency of patients with severe disability was significantly lower in the hemodilution group on days 8 and 21. Plasma viscosity (measured in 11 patients) was not affected by infusions of dextran 40. Vigorous hypervolemic hemodilution in patients with acute ischemic stroke is well tolerated and improves early neurologic outcome with an effect lasting at least 3 months.",
"The effects of intravenous glycerol in elderly patients with recent onset of acute ischaemic stroke were evaluated in a double-blind randomised controlled trial. 173 patients received either 500 ml of a 10% solution of glycerol in physiological saline or 500 ml of physiological saline administered intravenously over 4 h daily for 6 consecutive days. The number of deaths within the first week was 10 (12%) in the glycerol group versus 26 (30%) in the controls. Subsequent mortality up to 12 months was similar in the two groups and a survival analysis confirmed a beneficial effect of treatment (p less than 0.02). The neurological and functional recovery of survivors, their length of hospital stay, and the proportion able to return to live in their own home were similar in the two groups. The improvement in survival time with glycerol was achieved without serious adverse effects and without an increase in the proportion of survivors with severe residual disability.",
"Hypervolemic hemodilution (HH) with hydroxyethyl starch (HES) significantly increases cerebral blood flow and thus may reduce ischemic tissue damage in the penumbra zones when given within the therapeutic time window. The objective of this study was to investigate the safety of a 10% solution of HES 130/0.4 versus 0.9% saline solution in acute ischemic stroke by the incidence of adverse events (AEs).\n In a controlled, double-blind, randomized, multicenter, phase II, parallel-group study, 106 patients with acute ischemic stroke received high-dose HH with HES 130/0.4 or placebo within 6 h of symptom onset with a randomization ratio of 2:1 in favor of HES therapy.\n There were no significant differences between the groups with regard to the incidence of the specific AEs (cardiovascular events, bleeding complications, allergic reactions) assessed over days 1-30, or mortality over days 1-8. In addition, global tests of efficacy showed a trend towards a better functional outcome with HES therapy; however, the study was not designed to prove efficacy.\n High-dose HH with HES or NaCl was generally safe and well tolerated. Safety profiles were similar for the two treatment groups, and there was a nonsignificant trend towards a better functional outcome with HES therapy.\n Copyright 2002 S. Karger AG, Basel",
"Patients with acute ischemic stroke were randomized less than 24 hours after onset to standard (S) therapy (n = 43) or to hypervolemic hemodilution (HH) with pentastarch (n = 45). The therapeutic goal of hypervolemic hemodilution was to rapidly reduce hematocrit to 33%, to raise cardiac output, and to continue hypervolemic hemodilution for 3 days. A graded neurologic examination was scored by a blinded observer at randomization (baseline), at the end of treatment or after 72 hours, and at a 3-month follow-up; each patient was also rated using Barthel's disability scale at the 3-month follow-up. Group demographics and results of the graded neurologic examination were similar at baseline, except that the HH group contained twice the number of patients with severe strokes and fewer patients randomized within 12 hours compared with the S group. The HH group improved an average of 7 points in neurologic score from baseline to the end of treatment (the S group deteriorated 1 point) and 24 points by the 3-month follow-up (the S group improved 16 points; p = 0.11). The HH group reached an average Barthel disability scale index of 85 while the S group averaged 70 (p = 0.8). Deaths associated with cerebral edema occurred in five patients with severe stroke (four in the HH group vs. one in the S group, p = 0.36). The following subgroups of HH patients showed better overall improvement in neurologic scores: patients entered within 12 hours after stroke onset, patients with a 15% decrease in hematocrit, and patients with a 10% increase in cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)",
"Hemodilution in the acute phase of ischemic stroke is still controversial. Multicenter studies have failed to demonstrate any benefit. The present study focuses attention on analysis of circulation in stroke and on individual restabilization of circulation.\n The Amsterdam Stroke Study is a prospective, single-center, randomized clinical trial (n = 300). Normovolemic hemodilution is accomplished in a customized procedure by administration of 20% albumin plus crystalloids under hemodynamic and rheological monitoring in the acute phase of stroke. All patients receive general intensive care treatment and monitoring with a pulmonary artery catheter. This custom-tailored fluid therapy is guided on the basis of a target pulmonary capillary wedge pressure (12 +/- 3 mm Hg) and hematocrit (0.32 +/- 0.02). The control group receives only customized rehydration by infusion of crystalloids.\n We obtained significant (p less than 0.05) reduction in mortality at 3 months (from 27% to 16%) and an increase in independence at home (from 35% to 48%) after viscosity reduction by means of hemodilution with albumin in the subgroup with a hematocrit less than 0.45 (n = 201) (specific viscosity effect). We also obtained a significant (p less than 0.005) reduction in mortality at 3 months (from 27% to 8%) and an increase in independence (from 35% to 59%) after only rehydration with crystalloids in the subgroup with overt dehydration (hematocrit greater than or equal to 0.45; n = 51) as compared with the normal-hematocrit group without signs of dehydration (hematocrit less than 0.45; n = 103) (specific rehydration effect).\n This study may provide an explanation for the failures in former hemodilution trials and may re-establish proper hemodilution and rehydration as a valuable therapy in the acute phase of stroke, thus reducing mortality and improving independence after 3 months.",
"Approved treatment options for acute ischemic stroke in the United States and Canada are limited at present to intravenous tissue-type plasminogen activator, but bleeding complications, including intracranial hemorrhage, are a recognized complication.\n To evaluate the efficacy and safety of the defibrinogenating agent ancrod in patients with acute ischemic stroke.\n The Stroke Treatment with Ancrod Trial (STAT), a randomized, parallel-group, double-blind, placebo-controlled trial conducted between August 1993 and January 1998.\n Forty-eight centers, primarily community hospitals, in the United States and Canada.\n A total of 500 patients with an acute or progressing ischemic neurological deficit were enrolled and included in the intent-to-treat analysis.\n Patients were randomly assigned to receive ancrod (n=248) or placebo (n =252) as a continuous 72-hour intravenous infusion beginning within 3 hours of stroke onset, followed by infusions lasting approximately 1 hour at 96 and 120 hours. The ancrod regimen was designed to decrease plasma fibrinogen levels to 1.18 to 2.03 micromol/L.\n The primary efficacy end point was functional status, with favorable functional status defined as survival to day 90 with a Barthel Index of 95 or more or at least the prestroke value, compared by treatment group. Primary safety variables included symptomatic intracranial hemorrhage and mortality.\n Favorable functional status was achieved by more patients in the ancrod group (42.2%) than in the placebo group (34.4%; P=.04) by the prespecified covariate-adjusted analysis. Mortality was not different between treatment groups (at 90 days, 25.4% for the ancrod group and 23% for the placebo group; P=.62), and the proportion of severely disabled patients was less in the ancrod group than in the placebo group (11.8% vs 19.8%; P=.01). The favorable functional status observed with ancrod vs placebo was consistent in all subgroups defined for age, stroke severity, sex, prestroke disability, and time to treatment (< or = 3 or > 3 hours after stroke onset). There was a trend toward more symptomatic intracranial hemorrhages in the ancrod group vs placebo (5.2% vs 2.0%; P=.06), as well as a significant increase in asymptomatic intracranial hemorrhages (19.0% vs 10.7%; P=.01).\n In this study, ancrod had a favorable benefit-risk profile for patients with acute ischemic stroke.",
"To evaluate risk factor reduction and health-related quality of life following a 10-week cardiac rehabilitation programme in non-acute ischaemic stroke subjects.\n Single-blinded randomized control trial.\n Outpatient rehabilitation.\n Forty-eight community-dwelling ischaemic stroke patients (38 independently mobile, 9 requiring assistance, 1 non-ambulatory) were randomly assigned to intervention or control groups by concealed allocation.\n The trial consisted of a 10-week schedule with measures taken at weeks 1 and 10. Both groups continued usual care (excluding aerobic exercise); intervention subjects attended 16 cycle ergometry sessions of aerobic-training intensity and two stress-management classes.\n Cardiac risk score (CRS); VO(2) (mL O(2)/kg per minute) and Borg Rate of Perceived Exertion (RPE) assessed during a standardized ergometry test; Hospital Anxiety and Depression Scale (HADS); Frenchay Activity Index; Fasting Lipid Profiles and Resting Blood Pressure.\n Group comparison with independent t-tests showed significantly greater improvement at follow-up by intervention subjects than controls in VO(2) (intervention 10.6 +/-1.6 to 12.0 +/- 2.2, control 11.1 +/-1.8 to 11.1 +/-1.9 t=4.734, P<0.001) and CRS (intervention 13.4 +/-10.1 to 12.4 +/-10.5, control 9.4 +/-6.7 to 15.0 +/-6.1 t=-2.537, P<0.05). RPE rating decreased in intervention subjects (13.4 +/-12.2 to 12.4 +/-2.0) and increased in controls (13.8 +/-1.8 to 14.4 +/-1.6); Mann-Whitney U (U = 173.5, P<0.05). Within-group comparison showed significant decrease in the HADS depression subscale in the intervention group alone (5.1 +/-3.4 to 3.0 +/-2.8) (Wilcoxon signed ranks test Z=-3.278, P<0.001).\n Preliminary findings suggest non-acute ischaemic stroke patients can improve their cardiovascular fitness and reduce their CRS with a cardiac rehabilitation programme. The intervention was associated with improvement in self-reported depression.",
"Pathophysiological considerations and observational studies indicate that elevated body temperature, hypoxia, hypotension, and cardiac arrhythmias in the acute phase of ischemic stroke may aggravate brain damage and worsen outcome.\n Both units were organized with the same standard care and multidisciplinary approach to nursing and rehabilitation. A blinded observer assessed functional outcome at 3 months with the modified Rankin scale (mRS) and Barthel Index (BI). End points were (1) poor outcome, defined as either mRS > or =4 or BI <60 or the need for institutional care and (2) mortality.\n Fifty-four patients meeting the inclusion criteria were randomized. The groups were well matched for baseline characteristics, stroke subtype, stroke severity, vascular risk factors, and prognostic factors. Poor outcome was seen in 7 (25.9%) patients in the SCMU group and in 13 (48.1%) in the SU group (P=0.16). Mortality was lower in the SCMU group than in the SU group (1 [3.7%] vs 7 [25.9%]; odds ratio, 0.11 [95% CI, 0.02 to 0.96], P=0.05).\n This pilot study suggests that admission of acute stroke patients to an SCMU may reduce mortality and poor outcome. A larger trial is required to confirm these findings."
] |
The overall results of this review are compatible both with modest benefit and moderate harm of haemodilution therapy for acute ischaemic stroke. This therapy has not been proven to improve survival or functional outcome.
|
CD001894
|
[
"15665025",
"9513842",
"8825162",
"18413070",
"9557848",
"17094975",
"16613888",
"15284215",
"18927130",
"8981127",
"15905297",
"15266762",
"18325883",
"18439602",
"7784029",
"20607003",
"2255352",
"15823228",
"15294856",
"19268926",
"10575581",
"1547173"
] |
[
"A randomized double-blind controlled study of the efficacy of laser-assisted hatching on implantation and pregnancy rates of frozen-thawed embryo transfer at the cleavage stage.",
"Assisted hatching does not enhance IVF success in good-prognosis patients.",
"Does assisted hatching improve implantation rates after in vitro fertilization or intracytoplasmic sperm injection in all patients? A prospective randomized study.",
"Impact of assisted hatching on fresh and frozen-thawed embryo transfer cycles: a prospective, randomized study.",
"A prospective, randomized, double-blind study for the evaluation of assisted hatching in patients with advanced maternal age.",
"Laser assisted hatching in good prognosis patients undergoing in vitro fertilization-embryo transfer: a randomized controlled trial.",
"Laser-assisted hatching increases pregnancy and implantation rates in cryopreserved embryos that were allowed to cleave in vitro after thawing: a prospective randomized study.",
"A European multicentre prospective randomized study to assess the use of assisted hatching with a diode laser and the benefit of an immunosuppressive/antibiotic treatment in different patient populations.",
"A controlled randomized trial evaluating the effect of lowered incubator oxygen tension on live births in a predominantly blastocyst transfer program.",
"Enhancement of outcome from intracytoplasmic sperm injection: does co-culture or assisted hatching improve implantation rates?",
"Impact of assisted hatching on ART outcome in women with endometriosis.",
"Is assisted hatching beneficial in patients with recurrent implantation failures?",
"A randomized controlled clinical trial of 2295 ultrasound-guided embryo transfers.",
"Ultrasound guidance during embryo transfer: a prospective, single-operator, randomized, controlled trial.",
"A randomized study to assess the efficacy of the amniotic fluid index as a fetal admission test.",
"Does local endometrial injury in the nontransfer cycle improve the IVF-ET outcome in the subsequent cycle in patients with previous unsuccessful IVF? A randomized controlled pilot study.",
"[The benefit of external version in full-term breech presentation].",
"Implantation failures: success of assisted hatching with quarter-laser zona thinning.",
"Prospective randomised controlled trial of an infection screening programme to reduce the rate of preterm delivery.",
"A prospective, randomized, double-blinded study of assisted hatching in women younger than 38 years undergoing in vitro fertilization.",
"Clinical outcome of day 2 versus day 3 embryo transfer using serum-free culture media: a prospective randomized study.",
"Randomized trial of amniotomy in labour versus the intention to leave membranes intact until the second stage."
] |
[
"Assisted hatching (AH) in fresh embryo transfer (ET) cycles increases the implantation and pregnancy rates, especially in women with a poor prognosis, repeated implantation failures and in older women. Little information exists in the literature regarding the role of AH in frozen-thawed embryo transfer (FET) cycles.\n Embryos were cryopreserved at the cleavage stage. On the day of FET, 160 patients were randomized according to a computer-generated randomization list in sealed envelopes into the AH group and the control group. The patients and the clinicians were blinded to the group assigned. In the AH group, the outer half of the zona pellucida over a quarter of the diameter of zona was removed using a 1480 nm non-contact laser.\n The two groups were comparable in terms of demographic characteristics, ovarian response of the stimulated cycle and quality of fresh and frozen-thawed embryos. No differences in implantation, pregnancy and multiple pregnancy rates were found between the two groups. There was a non-significant trend of a higher implantation rate in the AH group when the zona thickness was > or = 16 mm.\n Laser AH did not improve the implantation rate of FET cycles and should not be performed routinely in all frozen-thawed embryos at the cleavage stage.",
"The role of assisted hatching in good-prognosis IVF patients was evaluated in a prospective, randomized, controlled pilot study, which was followed by a retrospective observational series.\n After assisted hatching was proved successful in a mouse embryo study, 20 good-prognosis IVF patients were randomly assigned to either assisted hatching (13) or no assisted hatching (7; the controls). Following this series, 27 good-prognosis IVF patients were retrospectively evaluated to determine the outcome with assisted hatching.\n In the prospective study, clinical pregnancies resulted from 3 (23%) of 13 patients in the hatching group, compared to 3 (43%) of 7 in the control group. Implantation rates were similar: 9.6% in the hatching group and 10.7% in the controls. In the retrospective series, the 11.1% implantation rate with assisted hatching was significantly less than the 42.9% implantation rate seen with traditional IVF.\n Implantation and pregnancy rates are high in young women undergoing traditional IVF. Assisted hatching is not beneficial in these patients.",
"Preliminary data from some research centers indicate that assisted hatching might be of value to increase embryo implantation rate in the human, at least in selected cases. It is not clear, however, whether this technique would be of benefit for all patients undergoing an embryo transfer. We therefore performed a prospective randomized study to evaluate the effect of assisted hatching on the implantation rate in our in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) program.\n In total, 120 couples undergoing an embryo transfer were randomized between two groups: in one group no assisted hatching was performed (AH-), whereas in the other group the embryos selected for transfer were subjected to partial zona dissection (PZD) immediately prior to the transfer (AH+). Using a computer-generated minimization procedure, patients were allocated to one of the two groups according to four pre-selected criteria: the number of embryos transferred, the cumulative score of transferred embryos, the age of the patient, and the use of ICSI.\n Pregnancy and implantation rates in the AH+ and AH- groups were, respectively, 42.1 versus 38.1% and 17.9 versus 17.1%.\n From our data we conclude that assisted hatching through partial zona dissection prior to embryo transfer does not improve pregnancy and embryo implantation rates in unselected patients undergoing IVF or ICSI.",
"The aim of this study was to determine if assisted hatching (AH) could improve the rates of pregnancy and implantation for both fresh and frozen-thawed embryo transfer cycles. A total of 760 fresh embryo transfer cycles and 200 frozen-thawed embryo transfer cycles were randomly assigned to either the treatment group (AH) or the control group (no AH). Zona thinning by laser was performed just before embryo transfer. In fresh embryo transfer cycles, the AH group and control group results were comparable. There were no significant differences in the rates of positive human chorionic gonadotrophin (HCG; 47.5 versus 48.8%), clinical pregnancy (42.4 versus 42.6%), or implantation (26.3 versus 25.2%) between the two groups. However, in frozen-thawed embryo transfer cycles, the rates of positive HCG (32.0 versus 17.0%), clinical pregnancy (25.0 versus 14.0%) and implantation (16.7 versus 7.3%) were significantly greater in the AH group than in the control group (P <: 0.05). The results of this investigation show that in the fresh embryo transfer cycles, laser-assisted hatching by zona thinning has no impact on the rates of positive HCG, clinical pregnancy and implantation, whereas in frozen-thawed cycles, assisted hatching by zona thinning significantly increases all three of these rates.",
"The objective of this study was to determine if assisted hatching improved the rates of implantation, clinical pregnancy and ongoing pregnancy for in-vitro fertilization (IVF) patients aged > or =36 years. On the day of oocyte aspiration, consenting patients were randomized according to whether all embryos underwent the hatching procedure (hatched; n = 41) or all embryos remained unhatched (controls; n = 48). Patients in both groups were treated with methylprednisolone and doxycycline starting on the day of oocyte retrieval and continuing for 4 days. The hatching procedure was performed approximately 55 h after insemination on all potential embryos for transfer and employed the release of acidified acid Tyrode's medium against the zona pellucida to create an opening approximately 20 microm in diameter. No significant differences were noted in the mean age, number of oocytes aspirated and number of embryos transferred between the hatched and control groups. In addition, no significant differences were observed in the rates of implantation (11.1 versus 11.3%), clinical pregnancy (39.0 versus 41.7%) and ongoing pregnancy (29.3 versus 35.4%) between the hatched and control groups respectively. These results suggest that assisted hatching may have no significant impact on IVF success rates in the patient population studied.",
"To evaluate whether assisted hatching improves clinical outcomes of embryo transfers to good prognosis patients, defined as patients < or =39 years with normal follicle-stimulating hormone (FSH) and E(2) levels, no more than one previous unsuccessful cycle of in vitro fertilization (IVF)-embryo transfer, and good embryo quality.\n Prospective randomized controlled trial.\n Private assisted reproductive technology (ART) center.\n One hundred ninety-nine good prognosis patients undergoing IVF-embryo transfer.\n In vitro fertilization followed by embryo transfer on day 3 after oocyte retrieval with or without assisted hatching using a 1,480-nm wavelength infrared laser.\n Clinical intrauterine pregnancy, spontaneous pregnancy loss, and live birth.\n Rates of clinical intrauterine pregnancy with fetal cardiac activity (53% vs. 54% per cycle), spontaneous pregnancy loss (13% vs. 16% per pregnancy), and live birth (47% vs. 46% per cycle) were very similar between treatment cycles with laser-assisted hatching and control cycles in which embryos were transferred without assisted hatching. There were no significant differences between treatment and control groups in any measured clinical outcome parameters.\n Assisted hatching does not improve clinical outcomes among good prognosis patients.",
"Cryopreservation of embryos may lead to zona hardening that may compromise in vivo hatching and implantation following thawing and transfer. Assisted hatching (AH) has been advocated as a means of assisting the natural hatching process and enhancing implantation.\n The aim of this study was to assess in a prospective randomized manner the effect of laser-assisted hatching (LAH) on implantation as well as clinical and multiple pregnancy rates (the primary outcome) after the transfer of frozen-thawed embryos. All embryos were thawed the day before transfer, and LAH was performed the next day on embryos that cleaved. Control group consisted of embryos that were transferred without AH.\n The performance of LAH significantly increased implantation (9.9 versus 20.1%, P < 0.01), clinical pregnancy (27.3 versus 40.9, P < 0.05) and multiple pregnancy rates (16 versus 40.3%, P < 0.07). In the LAH group, significantly more excess embryos that were left in culture hatched in vitro.\n LAH improves the outcome of frozen-thawed embryo transfer when performed before transfer on embryos that were allowed to cleave.",
"Assisted hatching (AH) techniques, designed for facilitating the embryo escape out of the zona pellucida (ZP) have been used in IVF centres since 1992. The initial indications for AH were patient's age, ZP thickness, high basal FSH and repeated IVF failures. Several retrospective and prospective studies assessing AH in these indications have given disparate results. Our aims were to evaluate the benefits of AH and immunosuppressive/antibiotic treatment (IA) in patients with either a poor prognosis of success, previous implantation failures or transfers of cryopreserved embryos.\n Four IVF centres allocated 426 patients, randomized for AH and IA, into four groups of AH indications between 1997 and 1999. AH was performed with a diode laser. ZP thickness, opening size and embryo score were recorded. Outcome measures were implantation and delivery rates.\n Patients coming for a first or third transfer of cryopreserved embryos and poor prognosis patients admitted for a first trial did not benefit from AH. Even patients with repeated implantation failures of fresh embryos did not gain significantly from AH.\n Among AH indications, absence of implantation after several transfers of good quality embryos remains the strongest patient selection criterion. Prescription of an immunosuppressive/antibiotic treatment is essential.",
"The potentially damaging effect of free O(2) radicals to cultured embryos may be reduced by adding scavengers to the culture media or by reducing the incubator O(2) levels. However, lowering the O(2) in the culture environment can be expensive, troublesome and may not be justifiable. The objective of this study was to evaluate the effect of lowered incubator O(2) tension on live birth rates in a predominately Day 5 embryo transfer program.\n Two hundred and thirty first-cycle women undergoing routine IVF or ICSI with ejaculated sperm were randomized in a prospective clinical trial and stratified for patient age and physician. Embryos of patients were randomly assigned for culture in either a 21% O(2) (atmospheric) or 5% O(2) (reduced) environment. Clinical endpoints monitored were rates of implantation, clinical pregnancy, live birth and blastocyst cryopreservation.\n Embryos cultured in a 5% O(2) environment consistently resulted in higher rates of live birth implantation (106/247, 42.9% versus 82/267, 30.7%; difference of 12.2% with 95% confidence interval (CI) of 3.9-20.3, P = 0.005) and live births (66/115, 57.4% versus 49/115, 42.6%; difference of 14.8% with 95% CI of 1.9-27.0, P = 0.043) when compared with rates among women whose embryos were cultured in an atmospheric O(2) environment.\n The overall increase in live births demonstrated by this study indicates that the effort and expense to culture embryos in a low-O(2) environment is justified. The study was registered at clinicaltrials.gov. NCT00708487.",
"In two separate prospectively randomized trials, intracytoplasmic sperm injection (ICSI) cycles were studied in a controlled manner to monitor the effects of either bovine oviductal epithelial cell co-culture (n = 119) or assisted hatching by zona drilling (n = 100). In the first study, immediately following ICSI, all eggs were placed directly either onto partial monolayers of bovine oviductal cells or into regular culture medium. Although the embryo developmental rate was apparently compromised in part by the presence of the co-culture cells, ultimately there were no significant differences in either the viable pregnancy rate (31.6% co-culture versus 29.0% control) or the embryonic implantation rate (11.4% co-culture versus 13.6% control). Assisted hatching also had no significant impact on ICSI cycle outcome in terms of either the viable pregnancy rate (30.0% assisted hatching versus 32.0% control) or the embryonic implantation rate (8.5% assisted hatching versus 13.5% control). However, in female patients aged > or = 35 years, assisted hatching appeared to convey a marginally significant benefit in terms of both the viable pregnancy rate (35.5% assisted hatching versus 11.1% control) and the embryonic implantation rate (10.3% assisted hatching versus 3.1% control). It seems that the overall improvement of ICSI cycle outcome cannot be achieved by the general application of either co-culture or assisted hatching. Nevertheless, it is possible that there remain specific patient groups that might benefit from selected use of either of these modalities.",
"Assisted hatching can improve the implantation rate in cycles with poor outcome. The impact of assisted hatching in embryos from women with endometriosis is not known. Therefore, the hypothesis that the implantation potential of embryos obtained from women with endometriosis can be improved with assisted hatching was tested.\n In a prospective randomized study, transfer embryos obtained from 60 women with endometriosis were hatched using a laser system and compared to embryos obtained from patients with the same diagnosis which were left intact (n = 30).\n The characteristics of cycles were similar between groups. The pregnancy (40% zona intact, 28.3% assisted hatching), and implantation rates (19.4% zona intact, 17.8% assisted hatching) did not differ in endometriosis cycles regardless of assisted hatching.\n Assisted hatching does not improve outcome in women with endometriosis undergoing assisted reproduction.",
"To assess the possible role of assisted hatching in patients with recurrent implantation failure during IVF cycles.\n Prospective randomized study.\n IVF unit of an academic medical center.\n Women who underwent IVF after at least three failed IVF-ET attempts.\n Patients were prospectively randomized to undergo assisted hatching of their embryos prior to their replacement by mechanical partial zona dissection.\n The study (assisted hatching) and control groups included 104 and 103 patients, respectively. There were no significant between-group differences in patient age, cause of infertility, mean number of previous IVF trials, number of oocytes retrieved, fertilization rate, or number of embryos transferred. No difference in pregnancy rate was noted on comparison of the whole study group, to the whole control group (21% and 27%, respectively). However, when the results were re-analyzed by age groups, assisted hatching was found to be harmful in the youngest group (< 34 years), significantly decreasing pregnancy rates (15% vs 35%, p < 0.05).\n Repeated implantation failure alone is not an indication for assisted hatching. Although assisted hatching appears to be effective in a selected group of older patients, in younger patients it may further hamper implantation and should be avoided.",
"We wanted to test the hypothesis that using abdominal ultrasound at the time of embryo transfer to guide replacement, improved pregnancy rates by at least 5%.\n An RCT in a large assisted conception unit. A pilot study and power calculation suggested that at least 2000 embryo transfers were required to demonstrate a difference of 5%, for a test with 80% power and Type 1 error 0.05. Randomization, data entry and analysis were arranged independently. Randomization was stratified for age and fresh/frozen embryo transfer. Analysis was by intention to treat.\n There was no difference in clinical pregnancy or live birth rates between the two groups. The clinical pregnancy rate for ultrasound-guided embryo transfer was 22% and for non-ultrasound-guided embryo transfer was 23% (odds ratio: 0.96; 95% confidence interval: 0.79-1.18).\n We set out to determine whether ultrasound-guided embryo transfer improved clinical pregnancy rates and live birth rates in assisted conception. We used an appropriately powered RCT design. We did not demonstrate a difference. This outcome is at odds with the UKs National Institute of Clinical Excellence recommendations for fertility treatment (Fertility Assessment and Treatment for People with Fertility Problems. London, UK: RCOG Press, 2004, 112.) which used a meta-analysis of four smaller trials (range 362-800 patients, totalling 2051 embryo transfers) to conclude that ultrasound should be offered. We suggest that the current Cochrane review should be updated with data from our trial and recommend that consideration is given to accounting for heterogeneity between the included trials.",
"To determine whether the implementation of ultrasound (US) guidance will improve the clinical outcomes of ET compared with the standard clinical touch method of embryo catheter placement.\n Prospective, single-operator, randomized, controlled trial.\n Saudi Center for Assisted Reproduction.\n Three hundred seventy-three women.\n Transcervical, intrauterine ET with or without US guidance.\n Primary outcomes were the live-birth/ongoing pregnancy and clinical pregnancy rates per randomized woman. Secondary outcomes were the incidences of difficult transfers, blood and/or mucus on the catheter tip, spontaneous miscarriages, and ectopic pregnancies.\n Demographics and cycle characteristics were not different between the two groups. The live-birth/ongoing pregnancy rate was significantly higher in the US ET group (68 of 183, 40.98%) than in the clinical touch ET group (50 of 190, 28.42%) (odds ratio = 1.66, 95% confidence interval 1.07-2.57). In addition, there was a significantly higher number of clinical pregnancies in the US ET group (75 of 183, 40.98%) than in the clinical touch ET group (54 of 190, 28.42%) (odds ratio = 1.75, 95% confidence interval 1.14-2.69). Secondary outcomes were not significantly different between the two groups.\n Ultrasound-guided ET significantly increases ongoing pregnancy/live-birth and clinical pregnancy rates compared with the clinical touch method.",
"To determine whether there is a difference in the incidence of abdominal delivery for presumed fetal distress in women who have an intrapartum fluid index assessment and those who do not.\n Over a 7-month period, parturients at 26-42 weeks' gestation and in early labor were randomized to the study (measured amniotic fluid index [AFI] on admission) or a control group (no sonographic assessment of amniotic fluid [AF] volume). The labor and delivery staff were aware of the AFI results of the study subjects. All patients had continuous electronic fetal monitoring, and none had an abnormal tracing on admission. Student t test or chi 2 was used for statistical analysis. P < .05 was considered significant.\n The study (N = 447) and control groups (N = 436) had similar maternal demographics as well as medical and obstetric complications. In the study group, the incidence of abdominal delivery for fetal distress (29 of 447) was significantly higher than among controls (14 of 436) (P = .02; relative risk 1.3, 95% confidence interval 1.1-1.7). Among parturients who had abdominal delivery for fetal distress, the decision-to-incision times (mean +/- standard deviation) were similar for parturients who had undergone assessment of AFI and those who had not (38.5 +/- 14.7 versus 32.5 +/- 14.7 minutes, respectively; P = .47). Mean birth weight, incidence of low birth weight, macrosomia, Apgar scores less than 7, and the number of admissions to the neonatal intensive care unit were not significantly different in the two groups.\n Patients having an intrapartum assessment of AFI as a fetal admission test are significantly more likely to have abdominal delivery for presumed fetal distress. However, the decision-to-incision time is not decreased and the perinatal outcome is not improved if the status of AF volume is known for patients in early labor.",
"Management of repeated implantation failure despite transfer of good-quality embryos still remains a dilemma for ART specialists. Scrapping of endometrium in the nontransfer cycle has been shown to improve the pregnancy rate in the subsequent IVF/ET cycle in recent studies.\n The objective of this randomized controlled trial (RCT) was to determine whether endometrial injury caused by Pipelle sampling in the nontransfer cycle could improve the probability of pregnancy in the subsequent IVF cycle in patients who had previous failed IVF outcome.\n Tertiary assisted conception center.\n Randomized controlled study.\n 100 eligible patients with previous failed IVF despite transfer of good-quality embryos were randomly allocated to the intervention group and control groups. In the intervention group, Pipelle endometrial sampling was done twice: One in the follicular phase and again in the luteal phase in the cycle preceding the embryo transfer cycle.\n The primary outcome measure was live birth rate. The secondary outcome measures were implantation and clinical pregnancy rates.\n The live birth rate was significantly higher in the intervention group compared to control group (22.4% and 9.8% P = 0.04). The clinical pregnancy rate in the intervention group was 32.7%, while that in the control group was 13.7%, which was also statistically significant (P = 0.01). The implantation rate was significantly higher in the intervention group as compared to controls (13.07% vs 7.1% P = 0.04).\n Endometrial injury in nontransfer cycle improves the live birth rate, clinical pregnancy and implantation rates in the subsequent IVF-ET cycle in patients with previous unsuccessful IVF cycles.",
"We report a randomised controlled trial of external version in 52 women with breech presentation after 36 weeks' gestation; 83% gave informed consent to undergo the management to which they had been randomized. Only 5% of initial attempts without tocolysis succeeded, but 31% of the failures subsequently had a successful version under tocolysis. External version resulted in a small decrease in the frequency of breech presentation at birth (64% vs. 74%), and in an unexpected increase in the caesarean section rate (28% vs. 11%). The increase in caesarean section rate could be attributed to failed versions, which apparently greatly influenced the choice between abdominal and vaginal delivery. Our findings and data from similar research suggest that benefits of external version at term may not apply to populations with a low caesarean rate, unless versions are carried out with maximal efficiency (which, on the basis of available data, would imply tocolysis) or so indifferently that failed attempts do not influence the choice between abdominal and vaginal delivery.",
"Implantation failure after IVF is one of the factors associated with a reduced chance of pregnancy for some patients. Assisted hatching methodologies are designed to facilitate the embryo's escape from the zona pellucida, and this strategy has been suggested as a means of improving pregnancy rates in patients with previous implantation failure. The aim of this prospective and randomized study was to evaluate the efficacy of quarter-laser zona thinning assisted hatching (qLZT-AH) in improving the implantation of embryos in patients with previous implantation failure. A total of 150 patients with a history of previous implantation failure were treated with intracytoplasmic sperm injection, and allocated into two groups: group 1, only one previous implantation failure, and group 2, repeated implantation failures. The patients in each group were randomized at the time of embryo transfer into a control group (no qLZT-AH) or experimental group where qLZT-AH was performed. For patients with repeated implantation failures, the implantation rate in those who received laser-thinned embryos was significantly higher (P = 0.02) than in those whose embryos were not laser-thinned (10.9 and 2.6% respectively). However, this difference was not observed in patients who presented with only one previous implantation failure. The data demonstrate that qLZT-AH is an effective strategy for improving the implantation of embryos in patients with repeated implantation failures.",
"To evaluate whether a screening strategy in pregnancy lowers the rate of preterm delivery in a general population of pregnant women.\n Multicentre, prospective, randomised controlled trial.\n Non-hospital based antenatal clinics.\n 4429 pregnant women presenting for their routine prenatal visits early in the second trimester were screened by Gram stain for asymptomatic vaginal infection. In the intervention group, the women's obstetricians received the test results and women received standard treatment and follow up for any detected infection. In the control group, the results of the vaginal smears were not revealed to the caregivers.\n The primary outcome variable was preterm delivery at less than 37 weeks. Secondary outcome variables were preterm delivery at less than 37 weeks combined with different birth weight categories equal to or below 2500 g and the rate of late miscarriage.\n Outcome data were available for 2058 women in the intervention group and 2097 women in the control group. In the intervention group, the number of preterm births was significantly lower than in the control group (3.0% v 5.3%, 95% confidence interval 1.2 to 3.6; P = 0.0001). Preterm births were also significantly reduced in lower weight categories at less than 37 weeks and <or= 2500 g. Eight late miscarriages occurred in the intervention group and 15 in the control group.\n Integrating a simple infection screening programme into routine antenatal care leads to a significant reduction in preterm births and reduces the rate of late miscarriage in a general population of pregnant women.",
"To determine whether assisted hatching is beneficial to IVF patients younger than 38 years whose embryos have a thickened zona pellucida (ZP).\n Prospective, randomized, double-blinded, crossover study.\n University-based infertility center.\n One hundred twenty-one women less than 38 years of age, undergoing IVF at Washington University between April 2004 and February 2007, with ZP thickness > or =13 microm for any embryos.\n Measurement of ZP thickness in embryos undergoing IVF; randomization of women with embryos with ZP thickness > or =13 microm to no procedure or assisted hatching performed by acidic Tyrode's solution.\n Clinical intrauterine pregnancy rate, implantation rate, spontaneous pregnancy loss, and live birth rate.\n Baseline characteristics and ZP thickness were not significantly different between the two study arms (hatched and unhatched). No significant differences were observed between hatched and unhatched patients in the rates of clinical pregnancy (47% vs. 50% respectively) or live birth (46% vs. 45% respectively). Further, no significant differences were noted between hatched and unhatched groups in rates of spontaneous abortions, monozygotic twinning, dizygotic twinning, chromosomal abnormalities, or ectopic gestations. In addition, mean ZP thickness did not have a significant effect on pregnancy.\n In patients younger than 38 years with embryos with ZP thickness of > or =13 microm, assisted hatching does not improve the rates of implantation, clinical pregnancy, or live birth, and thus does not appear to offer any benefit to patients in this age group undergoing IVF.\n Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.",
"The objective was to evaluate whether extending the embryo culture period from 2 to 3 days would yield a more optimal selection of viable embryos, thereby increasing the implantation and live birth rates.\n Patients undergoing in vitro fertilization with at least one oocyte fertilized were prospectively randomized to 2 or 3 days of embryo culture in serum-free media. On the basis of their morphology and cleavage rate, a maximum of three embryos was selected for transfer.\n Embryos transferred on day 2 or day 3 were similar morphologically, however, a higher proportion of retarded embryos was observed on day 3. The implantation rate was 15.8 and 14.3% for day 2 and day 3 transfers, respectively. The increase in live birth rate from 18.5 to 22.6%, possibly suggesting a better embryo selection on day 3, was not statistically significant.\n Extending the embryo culture period from 2 to 3 days had no effect on implantation and live birth rates.",
"To compare by randomized prospective clinical trial the outcome of labours which are managed with the intention to leave the membranes intact, compared with the practice of elective artificial rupture of the membranes (ARM) in early established labour.\n Prospective randomized controlled trial of low risk women admitted in spontaneous labour, with intact membranes.\n The labour ward of St. James's University Hospital, Leeds, UK.\n 362 women in spontaneous labour with intact membranes and no evidence of fetal distress, between 37 and 42 weeks gestation. During the course of the trial it was found that some randomization cards could not be accounted for and a system of daily checks was instituted. The results were analysed for all recorded women (n = 362) and after institution of the more rigorous system (n = 120).\n The duration of each phase of labour, epidural rate, prevalence of an abnormal cardiotocograph (CTG) (assessed blind), method of delivery and neonatal outcome.\n 178 of the 183 women (97%) in the ARM group had their membranes ruptured in early labour, and 83 (46%) of the 179 women allocated to non-intervention had ARM performed at some stage. A significant decrease in the duration of labour (mean 8.3, SD 4.1 h vs mean 9.7, SD 4.8 h, n = 156; P = 0.05) was found amongst primigravidae allocated to ARM when compared with non intervention. The duration of the second stage of labour was unaffected. In the ARM group the epidural rate was higher and labour was more often complicated by CTG abnormalities. There were no differences in the method of delivery, fetal condition at birth (cord blood lactate, Apgar score) or postpartum pyrexia between the ARM and non-intervention groups. The same trends were observed when analysis was confined to women entered into the trial after the system of rigour was instituted.\n Routine ARM results in labour that is slightly shorter than if the membranes are allowed to rupture spontaneously but more epidurals are used suggesting that labour is more painful. There are fewer fetal heart rate abnormalities if the membranes are left intact but amniotomy has no effect on fetal condition at birth."
] |
This update has demonstrated that whilst assisted hatching (AH) does appear to offer a significantly increased chance of achieving a clinical pregnancy, the extent to which it may do so only just reaches statistical significance. The 'take home' baby rate was still not proven to be increased by AH. The included trials provided insufficient data to investigate the impact of AH on several important outcomes. Most trials still failed to report on live birth rates.
|
CD008137
|
[
"15333725",
"15582060",
"17244293"
] |
[
"Conditional cash transfers are associated with a small reduction in the rate of weight gain of preschool children in northeast Brazil.",
"Monetary incentives in primary health care and effects on use and coverage of preventive health care interventions in rural Honduras: cluster randomised trial.",
"Effects of Cash and Counseling on personal care and well-being."
] |
[
"Programs providing cash transfers to poor families, conditioned upon uptake of preventive health services, are common in Latin America. Because of the consistent association between undernutrition and poverty, and the role of health services in providing growth promotion, these programs are supposed to improve children's growth. The impact of such a program was assessed in 4 municipalities in northeast Brazil by comparing 1387 children under 7 y of age from program beneficiary households with 502 matched nonbeneficiaries who were selected to receive the program but who subsequently were excluded as a result of quasi-random administrative errors. Anthropometric status was assessed 6 mo after benefits began to be distributed, and beneficiary children were 0.13 Z-scores lighter (weight-for-age) than excluded children, after adjusting for confounders (P = 0.024). The children's growth trajectories were reconstructed by copying up to 10 recorded weights from their Ministry of Health growth monitoring cards and by relating each weight to the child's age, gender, and duration of receipt of the program benefit in a random effects regression model. Totals of 472 beneficiary and 158 excluded children under 3 y of age were included in this analysis. Each additional month of exposure to the program was associated with a rate of weight gain 31 g lower than that observed in excluded children of the same age (P < 0.001). This failure to respond positively to the program may have been due to a perception that benefits would be discontinued if the child started to grow well. Nutrition programs should guard against giving the impression that poor growth will be rewarded.",
"Scaling-up of effective preventive interventions in child and maternal health is constrained in many developing countries by lack of demand. In Latin America, some governments have been trying to increase demand for health interventions by making direct payments to poor households contingent on them keeping up-to-date with preventive health services. We undertook a public health programme effectiveness trial in Honduras to assess this approach, contrasting it with a direct transfer of resources to local health teams.\n 70 municipalities were selected because they had the country's highest prevalence of malnutrition. They were allocated at random to four groups: money to households; resources to local health teams combined with a community-based nutrition intervention; both packages; and neither. Evaluation surveys of about 5600 households were undertaken at baseline and roughly 2 years later. Pregnant women and mothers of children younger than 3 years old were asked about use of health services (primary outcome) and coverage of interventions such as immunisation and growth monitoring (secondary outcome). Reports were supplemented with data from children's health cards and government service utilisation data. Analysis was by mixed effects regression, accounting for the municipality-level randomisation.\n The household-level intervention had a large impact (15-20 percentage points; p<0.01) on the reported coverage of antenatal care and well-child check-ups. Childhood immunisation series could thus be started more opportunely, and the coverage of growth monitoring was markedly increased (15-21 percentage points; p<0.01. Measles and tetanus toxoid immunisation were not affected. The transfer of resources to local health teams could not be implemented properly because of legal complications.\n Conditional payments to households increase the use and coverage of preventive health care interventions.",
"To examine how a new model of consumer-directed care changes the way that consumers with disabilities meet their personal care needs and, in turn, affects their well-being.\n Eligible Medicaid beneficiaries in Arkansas, Florida, and New Jersey volunteered to participate in the demonstration and were randomly assigned to receive an allowance and direct their own Medicaid supportive services as Cash and Counseling consumers (the treatment group) or to rely on Medicaid services as usual (the control group). The demonstration included elderly and non-elderly adults in all three states and children in Florida.\n Telephone interviews administered 9 months after random assignment.\n Outcomes for the treatment and control group were compared, using regression analysis to control for consumers' baseline characteristics.\n Treatment group members were more likely to receive paid care, had greater satisfaction with their care, and had fewer unmet needs than control group members in nearly every state and age group. However, among the elderly in Florida, Cash and Counseling had little effect on these outcomes because so few treatment group members actually received the allowance. Within each state and age group, consumers were not more susceptible to adverse health outcomes or injuries under Cash and Counseling.\n Cash and Counseling substantially improves the lives of Medicaid beneficiaries of all ages if consumers actually receive the allowance that the program offers."
] |
Conditional cash transfer programmes have been the subject of some well-designed evaluations, which strongly suggest that they could be an effective approach to improving access to preventive services. Their replicability under different conditions - particularly in more deprived settings - is still unclear because they depend on effective primary health care and mechanisms to disburse payments. Further rigorous evaluative research is needed, particularly where CCTs are being introduced in low income countries, for example in Sub-Saharan Africa or South Asia.
|
CD008041
|
[
"1317294",
"7564725",
"7899379",
"16109110",
"7954760",
"10669900",
"11128825",
"12890127",
"8164015",
"9563208",
"15836564",
"9536565"
] |
[
"A study to compare oral sumatriptan with oral aspirin plus oral metoclopramide in the acute treatment of migraine. The Oral Sumatriptan and Aspirin plus Metoclopramide Comparative Study Group.",
"The effectiveness of combined oral lysine acetylsalicylate and metoclopramide compared with oral sumatriptan for migraine.",
"[Efficacy and tolerance of an effervescent aspirin-metoclopramide combination in the treatment of a migraine attack. Randomized double-blind study using a placebo].",
"Acetaminophen, aspirin, and caffeine versus sumatriptan succinate in the early treatment of migraine: results from the ASSET trial.",
"Combined oral lysine acetylsalicylate and metoclopramide in the acute treatment of migraine: a multicentre double-blind placebo-controlled study.",
"Efficacy and safety of sumatriptan 50 mg in patients not responding to standard care, in the treatment of mild to moderate migraine. The Sumatriptan 50 mg Italian Study Group.",
"Acetylsalicylic acid effervescent 1000 mg (Aspirin) in acute migraine attacks; a multicentre, randomized, double-blind, single-dose, placebo-controlled parallel group study.",
"Sumatriptan plus metoclopramide in triptan-nonresponsive migraineurs.",
"Oral sumatriptan compared with placebo in the acute treatment of migraine.",
"Efficacy and safety of sumatriptan tablets (25 mg, 50 mg, and 100 mg) in the acute treatment of migraine: defining the optimum doses of oral sumatriptan.",
"Aspirin is efficacious for the treatment of acute migraine.",
"Sumatriptan suppositories for the acute treatment of migraine. S2B351 Study Group."
] |
[
"In a double-blind, placebo-controlled study, the efficacy, safety and tolerability of 100 mg oral sumatriptan, given as a dispersible tablet, was compared with that of 900 mg oral aspirin plus 10 mg oral metoclopramide in the acute treatment of migraine. A total of 358 patients treated up to three migraine attacks within 3 months, recording clinical information on a diary card. In attack 1, headache relief after 2 h, defined as a reduction in severity from severe or moderate pain to mild or no pain, was recorded in 56% (74/133) of patients who took sumatriptan and 45% (62/138) of patients who took aspirin plus metoclopramide (p = 0.078). This analysis of the primary efficacy end point was not statistically significant. However, for attacks 2 and 3 (secondary end points), headache relief was achieved in 58 versus 36% of patients (p = 0.001) and 65 versus 34% of patients (p less than 0.001), respectively. Relief from nausea, vomiting, photophobia and phonophobia was similar in both treatment groups. Rescue medication was required by fewer patients treated with sumatriptan than by those who received aspirin plus metoclopramide (attack 1, 34 versus 56%, p less than 0.001; attack 2, 32 versus 51%, p = 0.001, and attack 3, 35 versus 54%, p = 0.001). Sumatriptan also produced a faster improvement and resolution of migraine attacks. Comparing the sumatriptan and aspirin plus metoclopramide treatment groups, complete resolution of the attack occurred within 6 h in 32 versus 19% (attack 1), 35 versus 23% (attack 2) and 32 versus 20% of patients (attack 3).(ABSTRACT TRUNCATED AT 250 WORDS)",
"Aspirin is commonly used to treat migraine attacks, although sumatriptan, a much more expensive treatment, is also effective. We compared a combination of lysine acetylsalicylate (equivalent to 900 mg aspirin) and 10 mg metoclopramide (LAS+MTC) with oral sumatriptan (100 mg) and placebo in 421 patients with migraine. LAS+MTC was as effective as sumatriptan with a decrease of headache from severe or moderate to mild or none of 57% and 53%, respectively, for the first migraine attack treated. Both treatments were better than placebo (success rate 24%, p < 0.0001). LAS+MTC was significantly more effective in the treatment of nausea than sumatriptan (p < 0.0001) and was better tolerated (adverse events in 18% and 28%, respectively, p < 0.05). LAS+MTC is as effective as sumatriptan in the treatment of migraine attacks. It is also much cheaper.",
"A double blind, randomized, multicenter, parallel group study was carried out to compare the efficacy and tolerance of aspirin 900 mg-metoclopramide 10 mg effervescent association (AAM) with those of placebo in the treatment of acute migraine attack. All patients were selected according to the International Headache Society criteria.\n A total of 303 out-patients with an acute migraine attack were treated orally with either AAM (n = 152) or placebo (n = 151).\n The aspirin-metoclopramide association was significantly more effective than placebo at relieving headache (principal criterion) within 2 h of treatment (54.3% versus 25.9% : p < 0.001), producing entire resolution of acute migraine attack (14.2% versus 5.3% : p = 0.017), reducing the percentage of patients requiring rescue medication (44.3% versus 63.2% : p = 0.001) and increasing the percentage of patients able to resume their usual activities (44.1% versus 22.1% : p = 0.003). AAM also provided more frequent relief from associated symptoms as compared with placebo (37.4% versus 22.1% : p = 0.006). The therapeutic efficacy was rated as good or excellent by 39.7% of patients in the AAM group compared with 20.7% in the placebo group (p < 0.001). Moreover 64.2% of AAM treated patients said they would be prepared to take the treatment again compared with 46.4% who received placebo (p < 0.001). The percentage of patients reporting adverse events was not different between the two treatments (20.4% AAM versus 18.5% placebo : p = 0.684). The most commonly reported symptoms were gastro-intestinal disorders. Similar number of gastralgia occurred with AAM (n = 4) and placebo (n = 3).\n It is concluded that the aspirin-metoclopramide association may be used as a first intention treatment of acute migraine attack in out-patients.",
"To address the need for a rigorous, direct comparison of prescription and over-the-counter (OTC) migraine drugs and to expand the database on early treatment of migraine.\n Most people who experience migraine use OTC medications to treat their symptoms, but no head-to-head clinical trials comparing these agents with prescription migraine therapies have been published. In addition, even though most migraineurs treat early in the attack, few studies have been conducted to reflect this treatment pattern.\n We compared a combination of nonprescription migraine medication (acetaminophen 500 mg, aspirin 500 mg, and caffeine 130 mg) with a prescription migraine product (50 mg sumatriptan) in a randomized, controlled clinical trial in which subjects treated at the first sign of a migraine attack. Subjects who reported vomiting during more than 20% of migraine episodes or who required bedrest during more than 50% of migraine episodes were excluded from the study. Of the 188 subjects randomized, 171 took study medication and were included in the analysis.\n The combination of acetaminophen, aspirin, and caffeine was significantly more effective (P > .05) than sumatriptan in the early treatment of migraine, as shown by superiority in summed pain intensity difference, pain relief, pain intensity difference, response, sustained response, relief of associated symptoms, use of rescue medication, disability relief, and global assessments of effectiveness. An additional, larger clinical trial is needed to confirm these results.",
"This multicentre, double-blind, randomized, placebo-controlled, parallel study was designed to evaluate the efficacy of combined oral lysine acetylsalicylate and metoclopramide (LAS-MCP) in the acute treatment of migraine attacks. A total of 266 patients, 18-65 years old, with two to six attacks of migraine with or without aura (IHS criteria) per month were included. The patients had to treat two migraine attacks with LAS-MCP (1620 mg lysine acetylsalicylate--the equivalent of 900 mg aspirin--combined with 10 mg metoclopramide) or placebo. The main outcome measure was headache relief (reduction in headache severity from grade 3 or 2--severe or moderate--to grade 1 or 0--mild or none) 2 h after treatment. LAS-MCP was superior to placebo for headache relief (56% vs 28%) and for the following secondary outcome measures: complete headache relief (18% vs 7%; p < 0.001), nausea (28% vs 44%; p < 0.001), vomiting (3% vs 11%; p = 0.001), use of rescue medication (47% vs 68%; p < 0.001), global efficacy judged as good or excellent (32% vs 14%; p < 0.001). The tolerability was considered as good in 94% of treated attacks in both groups. Combined oral lysine acetylsalicylate and metoclopramide is an effective and well-tolerated acute treatment of migraine attacks.",
"The tolerability and efficacy of oral sumatriptan 50 mg for the treatment of mild to moderate migraine attacks were assessed in a double-blind, multicenter placebo-controlled study on a group of patients who had not responded sufficiently to analgesic preparations. Three-hundred-and-twenty-eight migraine sufferers treated a first migraine attack with a nontriptan standard care medication: a mixture containing phenazone, butalbital and caffeine (optalidon) or indomethacin plus prochlorperazine plus caffeine (difmetre) or paracetamol 100 mg (tachipirine), depending on their habits. Of these patients, 32.6% reported headache relief with this treatment and were not included in phase II of the study. The 219 patients not reporting relief during the first phase of the study entered the second phase and were randomized to sumatriptan 50 mg or to placebo; 167 of these patients treated a second attack according to the protocol and were evaluated for efficacy. Of the patients with migraine taking sumatriptan, 58% reported headache relief compared with 35% of placebo-treated patients (p = 0.008). The reduction of nausea and vomiting was significantly better in the sumatriptan group. No differences were detected for the recurrence rate, while rescue medication was used more by the placebo group. The safety profile of sumatriptan 50 mg was confirmed. This study demonstrates the usefulness of this dose of oral sumatriptan against the pain and the accompanying symptoms of mild and moderate migraine.",
"In this multicentre, randomized, double-blind, single-dose study a total of 374 patients generally suffering from migraine attacks suitable for treatment with non-prescription drugs, received either oral acetylsalicylic acid effervescent 1000 mg (ASAE) or effervescent placebo for the treatment of an acute migraine attack. Of the 343 patients fulfilling the criteria for efficacy analysis 169 patients took acetylsalicylic acid and 174 placebo. Response rates (reduction of headache severity from severe or moderate to mild or no pain at 2 h after administration) were 55.0% for acetylsalicylic acid and 36.8% for placebo (P < 0.001). Twenty-nine percent of patients in the active treatment group were pain-free after 2 h compared with 16.7% in the placebo group (P = 0.007). No headache recurred within 24 h post-dose in 84.6% of patients in the active group and in 85.1% of patients in the placebo group. Effervescent placebo reduced nausea and vomiting to the same degree as the active drug. Adverse events of acetylsalicylic acid (8.3%) were generally mild or moderate and comparable to those of placebo (2.9%). This study shows that oral ASAE is safe and effective for the treatment of acute migraine attacks.",
"We evaluated the effectiveness of combination treatment using sumatriptan plus metoclopramide versus sumatriptan alone for the treatment of acute migraine. The patients who were treated had failed to respond to triptans in the past despite adequate doses on at least 2 separate trials of the same triptan or 2 trials involving different triptans.\n There is limited evidence that dopaminergic antagonists may benefit the migraineur by relieving migraine pain and associated symptoms. The exact mechanism of action in migraine is unknown. The postulated action is the inhibition of dopaminergic overactivity. A dopaminergic antagonist, metoclopramide, may improve the efficacy of a 5-HT1B/1D agonist, sumatriptan.\n In this double-blind, randomized, crossover study, 16 adult migraineurs fulfilling International Headache Society (IHS) criteria for migraine with or without aura who had failed to receive adequate relief from triptans treated one migraine with each treatment: sumatriptan 50 mg plus metoclopramide 10 mg or sumatriptan 50 mg plus placebo to match metoclopramide. Patients treated their migraines when they were moderate or severe in intensity and recorded pain severity and symptoms prior to treatment and 30, 60, 90, and 120 minutes and 24 hours after treatment.\n Thirteen women and 3 men (mean age, 40 years) completed the study; ie, treated 2 migraines (a total of 32 migraines), one attack with each treatment. Meaningful relief was attained in 10 (63%) of 16 migraines treated with the combination of sumatriptan 50 mg plus metoclopramide 10 mg compared with 5 (31%) of 16 migraines treated with sumatriptan 50 mg plus placebo. Headache response (moderate or severe to mild or no pain at 2 hours) was achieved in 7 (44%) of 16 migraines with the combination of sumatriptan 50 mg plus metoclopramide 10 mg compared with 5 (31%) of 16 migraines treated with sumatriptan 50 mg plus placebo. There did not appear to be a difference between treatment groups with respect to associated symptoms. The combination of sumatriptan 50 mg plus metoclopramide 10 mg was well tolerated.\n Combining sumatriptan with metoclopramide provided relief in some migraineurs who failed to achieve adequate relief with a triptan alone. It remains unknown whether initiating therapy when pain was mild or using a higher dose of sumatriptan (ie, 100 mg) would have provided additional benefit. Further studies are indicated.",
"This multicentre, double-blind, parallel-group study compared the efficacy, safety and tolerability of oral sumatriptan, given as a new film-coated tablet, with placebo in the acute treatment of migraine. Patients were randomised unequally (1:2) to receive placebo or sumatriptan. Eighty-eight patients received placebo (plus an optional dose 2 h later if the headache persisted plus a further optional dose for recurrence within 24 h) and 162 patients received sumatriptan 100 mg (plus an optional 100 mg dose at 2 h and an optional 100 mg dose within 24 h). Sumatriptan was significantly more effective than placebo at relieving headache (defined as reduction in severity from severe or moderate pain to mild or no pain) at 2 h (51% versus 31%, P = 0.003) and 4 h (71% versus 35%, P < 0.001). Fewer sumatriptan-treated patients required a second dose compared with placebo-treated patients (49% versus 74%, P < 0.001). More sumatriptan-treated patients were completely pain free compared with placebo-treated patients at both 2 h (24% versus 12%) and 4 h (48% versus 18). Patients receiving sumatriptan reported earlier onset of headache relief than patients receiving placebo. Headache relief in sumatriptan-treated patients was similar, irrespective of the type of migraine (with or without aura) or the time of treatment < or = 4 h or > 4 h after onset of migraine). Sumatriptan was more effective than placebo at relieving nausea, vomiting and photophobia/phonophobia. Few patients were evaluable for treatment of headache recurrence, and statistical analysis was not possible.(ABSTRACT TRUNCATED AT 250 WORDS)",
"That sumatriptan tablets are effective and well tolerated in the acute treatment of migraine has been established, but the relationship between dose and efficacy has not been adequately defined to date in clinical trials. This multinational double-blind trial (N = 1003) in which patients treated up to three migraine attacks with sumatriptan 25 mg, 50 mg, 100 mg, or placebo, with a second independently randomized dose for headache recurrence, evaluated the efficacy and tolerability of three doses of sumatriptan. The results demonstrate that all doses of sumatriptan were superior (P < 0.05) to placebo in reducing moderate or severe predose headache to mild or no headache 4 hours postdose for each of the three treated attacks; sumatriptan 50 mg and 100 mg were each superior (P < 0.05) to sumatriptan 25 mg 4 hours postdose for two of three attacks. Sumatriptan (all doses) was similarly effective at relieving nausea and photophobia or phonophobia or both and at reducing clinical disability. Headache recurrence was experienced by similar proportions of patients across treatment groups (35% to 48% after placebo; 26% to 39% after sumatriptan). Relief of recurrent headache 2 hours after the second dose of study medication occurred in greater percentages of patients using any dose of sumatriptan compared with patients using placebo to treat recurrence. The incidence of adverse events with 25-mg and 50-mg sumatriptan tablets was similar to the incidence with placebo and lower than the incidence with 100-mg sumatriptan tablets. These data provide the first demonstration from a large well-controlled clinical trial that both the 50- and 100-mg doses are more effective than the 25-mg dose and that the 50-mg dose is associated with a lower incidence of adverse events than the 100-mg dose.",
"More than 50% of migraine sufferers rely on over-the-counter medications for the treatment of migraine. Along with other over-the-counter products, aspirin is considered by the US Headache Consortium to be an option for first-line migraine treatment. This study assessed the efficacy and tolerability of aspirin versus placebo for the acute treatment of a single acute attack of migraine.\n This prospective, randomized, double-blind, parallel-group, placebo-controlled study evaluated the efficacy of a single, 1000-mg dose of aspirin for the treatment of acute moderate to severe migraine, with or without aura. Subjects recorded all study evaluations in a diary at baseline and at .5, 1, 2, 3, 4, 5, 6, and 24 hours after treatment. Pain was rated on a 4-point ordinal scale from no pain to severe pain. The primary efficacy end point was headache response at 2 hours. Secondary efficacy parameters included reduction of nausea, photophobia and phonophobia, pain intensity difference, and headache recurrence at 24 hours.\n Of 485 subjects enrolled, 409 took study medication and 401 treated a confirmed migraine attack (201 with aspirin and 200 with placebo). Baseline demographic and migraine characteristics were not significantly different between groups. The 2-hour headache response rate was 52% with aspirin versus 34% with placebo (P<.001). Aspirin was significantly more effective than placebo for pain reduction beginning 1 hour after dosing (P<.001) and continuing throughout the 6-hour evaluation period. Significantly (P<.05), more subjects were pain free from the 1-hour evaluation through the 6-hour evaluation. Of the aspirin-treated subjects, 20% were pain free at 2 hours versus only 6% of placebo-treated subjects. At 24 hours, the headache recurrence rate was 21.8% for aspirin (23 of 105 subjects) and 27.7% for placebo (19 of 68 subjects). Only 34% of aspirin-treated subjects needed rescue medication at 24 hours compared with 52% of placebo-treated subjects (P<.001). Aspirin was well tolerated, and adverse events were not significantly different between groups.\n This study demonstrates that aspirin is safe and effective for treatment of acute migraine in appropriately selected patients.",
"A randomised, double-blind, parallel-group, placebo-controlled trial was undertaken to assess the efficacy and tolerability of the sumatriptan suppository in 184 patients with acute migraine. Patients used a sumatriptan suppository (12.5 mg or 25 mg) or placebo at home for the treatment of a moderate or severe migraine attack and those who experienced headache recurrence within 24 hours of dosing had the option to repeat the dose. By 2 hours post-dose, 68% of patients in the sumatriptan 25 mg group and 47% of patients in the sumatriptan 12.5 mg group compared with 25% of placebo patients achieved headache relief. Relief rates 2 hours post-dose for nausea, vomiting, photophobia and phonophobia were similar to those reported 2 hours post-dose for headache. Post hoc review of the recurrence data showed that administration of a second suppository was effective in alleviating recurrent headache in over 80% of the sumatriptan-treated patients experiencing recurrence. No serious or unusual adverse events were reported, and the pattern and incidence of adverse events did not vary as a function of dose. These data demonstrate that the sumatriptan suppository is a well-tolerated, effective treatment for the acute treatment of migraine pain and its associated symptoms."
] |
We found no new studies since the last version of this review. Aspirin 1000 mg is an effective treatment for acute migraine headaches, similar to sumatriptan 50 mg or 100 mg. Addition of metoclopramide 10 mg improves relief of nausea and vomiting. Adverse events were mainly mild and transient, and were slightly more common with aspirin than placebo, but less common than with sumatriptan 100 mg.
|
CD004524
|
[
"15290737",
"20574649",
"8242109"
] |
[
"Efficacy of methotrexate in ankylosing spondylitis: a randomized, double blind, placebo controlled trial.",
"Etanercept (ETN) with methotrexate (MTX) is better than ETN monotherapy in patients with active rheumatoid arthritis despite MTX therapy: a randomized trial.",
"[A short-term randomized controlled study with methotrexate in rheumatoid arthritis]."
] |
[
"To evaluate the efficacy and safety of methotrexate (MTX) compared with placebo in patients with active ankylosing spondylitis (AS).\n This 24 week, double bind, randomized, placebo controlled trial compared the response between MTX 7.5 mg/week or placebo in patients with active AS. The primary outcome measure was a composite index of improvement in 5 of the following scales: severity of morning stiffness, physical well being, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), the Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S), and physician and patient global assessment of disease activity.\n Seventeen patients received MTX and 18 placebo. In the intention-to-treat analysis at 24 weeks, 53% of patients in the MTX group had a treatment response, compared with 17% in the placebo group (p = 0.03). We observed significant improvements with MTX in physical well being (p = 0.009), BASDAI (p = 0.02), BASFI (p = 0.02), physician global assessment (p < 0.001), patient global assessment (p = 0.03), and HAQ-S (p = 0.02). In the adjusted analysis only MTX determined the improvement in the primary outcome. At the end of the trial, one patient with MTX withdrew due to a lack of compliance, and one with placebo due to a lack of efficacy. We did not observe significant differences in rates of side effects between the 2 groups.\n MTX is safe and effective for patients with AS. Longterm studies are needed to evaluate the permanence of its benefit.",
"The superiority of the combination therapy of methotrexate (MTX) and anti-tumor necrosis factor (TNF) biological agents over anti-TNF monotherapy in MTX-naïve patients with rheumatoid arthritis (RA) has been demonstrated. We investigated the efficacy and safety of continuation versus discontinuation of MTX at the commencement of etanercept (ETN) in patients with active RA despite MTX therapy. In total, 151 patients with active RA despite treatment with MTX were randomized to either ETN 25 mg twice a week and MTX 6-8 mg/week (the E + M group) or ETN alone (the E group). Co-primary endpoints included the European League Against Rheumatism (EULAR) good response rate and the American College of Rheumatology (ACR) 50 response rate at week 24. Demographic and clinical features between groups at baseline were similar. The EULAR good response rates were significantly higher in the E + M group (52%) than in the E group (33%) at week 24 (p = 0.0001). Although the ACR50 response rate, one of the co-primary endpoints, and the ACR70 response rate at week 24 were not significantly greater in the E + M group (64 and 38%, respectively) than in the E group (48 and 26%, respectively), the ACR20 response rate was significantly greater in the E + M group (90%) than in the E group (64%; p = 0.0002). Safety profiles were similar for the groups. Thus, MTX should be continued at the commencement of ETN therapy, even in RA patients who show an inappropriate response to MTX.",
"Randomized, controlled and double-blind study of 36 patients aimed at the evaluation of the efficacy and toxicity of MTX in the treatment of rheumatoid arthritis. Twenty-eight patients completed the study period: 14 in the MTX group and 14 in the placebo group. The patients treated with MTX presented a statistically significant improvement (p < 0.05) in pain, grip strength and functional ability when compared to placebo treated patients. Mild adverse effects were observed in 4 patients treated with MTX and in 2 patients treated with placebo. These findings support other studies and give to methotrexate a relevant position in the treatment of rheumatoid arthritis, owing to its convenient posology, beneficial effectivity and favourable toxicity."
] |
There is not enough evidence to support any benefit of MTX in the treatment of AS. High-quality RCTs of larger sample sizes are needed to clarify the effect(s) of MTX on AS.
|
CD001084
|
[
"12172535",
"3046651",
"10506039",
"17438178",
"9057377",
"20402591",
"16177249",
"7933348",
"3881323"
] |
[
"A randomized, comparative pilot study of azithromycin versus benzathine penicillin G for treatment of early syphilis.",
"A double-blind randomized controlled trial on the use of prophylactic antibiotics in patients undergoing elective caesarean section.",
"Randomised, double blind placebo controlled trial of pentoxifylline in the treatment of venous leg ulcers.",
"A randomized, double-blind, placebo-controlled trial of pentoxifylline for the treatment of recurrent aphthous stomatitis.",
"Effectiveness of ampicillin and combination of penicillin and chloramphenicol in the treatment of pneumonias: randomized controlled trial.",
"A phase III equivalence trial of azithromycin versus benzathine penicillin for treatment of early syphilis.",
"Single-dose azithromycin versus penicillin G benzathine for the treatment of early syphilis.",
"Reduction of fever and streptococcal bacteremia in granulocytopenic patients with cancer. A trial of oral penicillin V or placebo combined with pefloxacin. International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer.",
"Double blind controlled trial of d-penicillamine in patients with primary biliary cirrhosis."
] |
[
"Penicillin is the only medication currently recommended for treatment of early syphilis in non-penicillin-allergic patients. Preliminary data suggest that azithromycin may be effective for syphilis therapy.\n This was a randomized, comparative pilot study of intramuscular injections of benzathine penicillin G and two oral azithromycin regimens for treatment of syphilis.\n We randomly assigned patients with early syphilis to treatment with either intramuscular injections of 2.4 million units of benzathine penicillin G or azithromycin administered orally, either as a single 2.0-g dose or as two 2.0-g doses given 1 week apart. Serological response to therapy was evaluated at 3, 6, 9, and 12 months following therapy. Participants whose rapid plasma reagin (RPR) test became nonreactive or whose RPR titer decreased > or =2 dilutions were classified as responding to therapy. When serological tests did not show a response to therapy, the treatment was classified as a failure if RPR titers increased > or =2 dilutions. Nonresponders were those whose serologic titers remained within +/-1 dilution of the initial RPR titer.\n Cumulative response rates were as follows: benzathine penicillin G, 86% (12 of 14); azithromycin, 2.0-g single dose, 94% (16 of 17); and azithromycin, two 2.0-g doses given 1 week apart, 83% (24 of 29). Therapy failed for one patient treated with benzathine penicillin and one patient treated with the two-dose azithromycin regimen, whereas in six patients the clinical manifestations of infection resolved but there was no serological response.\n Oral therapy with 2.0 g of azithromycin as a single dose or as two doses 1 week apart is a promising alternative to therapy with benzathine penicillin G for syphilis and should be studied further.",
"In a double-blind randomized controlled study 232 patients undergoing elective lower segment caesarean section were randomly allocated to receive a pre-operative prophylactic dose of a combination of crystalline penicillin and chloramphenicol or a placebo. The two groups were comparable in terms of patient characteristics and operation variables. The group receiving antibiotics had significantly fewer febrile and infectious morbid events and thus spent fewer days in hospital than the group receiving the placebo.",
"To determine whether pentoxifylline 400 mg (Trental 400) taken orally three times daily, in addition to ambulatory compression bandages and dressings, improves the healing rate of pure venous ulcers.\n Randomised, double blind placebo controlled trial, parallel group study of factorial design, permitting the simultaneous evaluation of alternative pharmaceutical, bandaging, and dressings materials.\n Leg ulcer clinics of a teaching and a district general hospital in southern Scotland.\n 200 patients with confirmed venous ulcers and in whom other major causal factors were excluded. Interventions: Pentoxifylline 400 mg three times daily or placebo.\n Complete healing (full epithelialisation) of all ulcers on the trial leg.\n Complete healing occurred in 65 of the 101 (64%) patients receiving pentoxifylline and 52 of the 99 (53%) patients receiving placebo.\n The difference in the healing rates between patients taking pentoxifylline and those taking placebo did not reach statistical significance.",
"To evaluate pentoxifylline for the treatment of recurrent aphthous stomatitis.\n A 60-day, randomized, double-blind, placebo-controlled trial with a 60-day no treatment follow-up.\n An oral medicine specialist referral center in Manchester.\n Forty-nine volunteers who passed the initial assessment for recurrent aphthous stomatitis entered a pretrial phase in which their eligibility for the trial phase of the study was assessed. Sixteen subjects were deemed ineligible, and 7 failed to attend or withdrew. The remaining 26 subjects were randomized to placebo or treatment. Six subjects withdrew because of adverse effects, and 1 was unavailable for follow-up.\n Pentoxifylline (also called oxpentifylline), 400 mg 3 times daily, or matching placebo.\n A reduction in the median pain score, ulcer size, number of ulcers, or total number of ulcer episodes.\n Patients taking pentoxifylline had less pain and reported smaller and fewer ulcers compared with baseline. Patients taking placebo reported no improvement in these variables. Patients taking pentoxifylline also reported more ulcer-free days than those taking placebo. However, the differences were small and, with the exception of median ulcer size (P = .05), did not reach statistical significance. Adverse effects were common with pentoxifylline, but not significantly different from those experienced by patients taking placebo.\n Although pentoxifylline may have some benefit in the treatment of recurrent aphthous stomatitis, the benefit is limited. It may have a role in the treatment of patients unresponsive to other treatments, but cannot yet be recommended as a first-line treatment.",
"To assess the effectiveness of ampicillin and a combination of benzyl penicillin and chloramphenicol in the treatment of pneumonias.\n Randomized controlled trial.\n Tertiary care hospital.\n Patients 5 months to 4 years old with pneumonias of < 2 weeks duration. Exclusion criteria included acute bronchiolitis, allergy to penicillin, postmeasles pneumonia or prior administration of trial antibiotics in full dose for more than 2 days.\n Patients were randomized to receive either ampicillin (100 mg/kg/day) or combination of benzyl penicillin (100,000 units/kg/day) and chloramphenicol (100 mg/kg/day). The outcome measure was cure rate.\n There were 52 and 49 patients in the ampicillin and the combination groups, respectively. There was no significant difference in the baseline characteristics between groups except, nasal flare and cyanosis which were less in benzyl penicillin plus chloramphenicol group. There was also no difference either in the primary outcome, cure rate or secondary outcomes (days for cure, duration of tachypnea, fever and grunt) in the two.\n Considering the potential toxicity of chloramphenicol and the number of injections and doses to be given for the combination, ampicillin as a single drug could be preferred for the treatment of pneumonias, in this part of the country.",
"Syphilis remains an important source of morbidity worldwide. Long-acting penicillin is the only therapy currently recommended for syphilis in much of the world. Because of hesitation to use penicillin for fear of anaphylaxis, there is a need for an effective, well-tolerated alternative to penicillin for syphilis therapy.\n This multicenter, randomized clinical trial was conducted in clinics for the treatment of persons with sexually transmitted diseases. We compared serological cure rates for human immunodeficiency virus (HIV)-negative persons with early syphilis treated with azithromycin at a dosage of 2.0 g administered orally as a single dose with cure rates for those treated with benzathine penicillin G at a dosage of 2.4 million units administered intramuscularly.\n A total of 517 participants were enrolled in the trial. In the intention-to-treat analysis, after 6 months of follow-up, serological cure was observed in 180 (77.6%) of 232 azithromycin recipients and 186 (78.5%) of 237 penicillin recipients (1-sided lower bound 95% confidence interval, 7.2%). Nonserious adverse events were more common among azithromycin recipients than they were among penicillin recipients (61.5% vs 46.3%), and such adverse events were accounted for, in large part, by self-limited gastrointestinal complaints.\n In this trial, the efficacy of azithromycin at a dosage of 2.0 g administered orally was equivalent to that of benzathine penicillin G for the treatment of early syphilis in persons without HIV infection.",
"Pilot studies suggest that a single, 2-g oral dose of azithromycin may be an alternative to a 2.4-MU intramuscular dose of penicillin G benzathine in the prevention and treatment of syphilis. We evaluated the efficacy of treatment with azithromycin in a developing country.\n A total of 328 subjects, 25 with primary and 303 with high-titer (a titer of at least 1:8 on a rapid plasmin reagin [RPR] test) latent syphilis, were recruited through screening of high-risk populations in Mbeya, Tanzania, and randomly assigned to receive 2 g of azithromycin orally (163 subjects) or 2.4 million units of penicillin G benzathine intramuscularly (165 subjects). The primary outcome was treatment efficacy, with cure defined serologically (a decline in the RPR titer of at least two dilutions by nine months after treatment) and, in primary syphilis, by epithelialization of ulcers within one or two weeks.\n The average age of participants was 27.0 years, 235 (71.6 percent) were female, and 171 (52.1 percent) were seropositive for human immunodeficiency virus. Cure rates were 97.7 percent (95 percent confidence interval, 94.0 to 99.4) in the azithromycin group and 95.0 percent (95 percent confidence interval, 90.6 to 97.8) in the penicillin G benzathine group (95 percent confidence interval for the difference, -1.7 to 7.1 percent), achieving prespecified criteria for equivalence. Cure rates were also similar three and six months after treatment in the two groups and in all subgroups. Cure rates at three months were 59.4 percent (95 percent confidence interval, 51.8 to 67.1) in the azithromycin group and 59.5 percent (95 percent confidence interval, 51.8 to 67.3) in the penicillin G benzathine group and at six months were 85.5 percent (95 percent confidence interval, 79.4 to 90.6) and 81.5 percent (95 percent confidence interval, 74.8 to 87.4), respectively.\n Single-dose oral azithromycin is effective in treating syphilis and may be particularly useful in developing countries in which the use of penicillin G benzathine injections is problematic. However, recent reports of azithromycin-resistant Treponema pallidum in the United States indicate the importance of continued monitoring for resistance.\n Copyright 2005 Massachusetts Medical Society.",
"To determine the effect of oral penicillin V combined with a fluoroquinolone (pefloxacin) on the occurrence of fever and streptococcal and other gram-positive coccal bacteremic infections in granulocytopenic patients with cancer.\n Prospective randomized double-blinded placebo-controlled prophylactic trial.\n Inpatient setting in multiple cooperating cancer centers.\n Convenience sample with a total of 551 granulocytopenic patients, 95% of whom had leukemia or underwent bone marrow transplantation.\n Penicillin V (500 mg twice a day) vs placebo given in combination with oral pefloxacin (400 mg twice a day).\n Occurrence of fever and/or infection.\n Fever or infection (without fever) developed in 190 (71%) of 268 evaluable patients in the penicillin arm compared with 213 (80%) of 268 evaluable patients in the placebo arm (P = .03; 95% confidence interval [CI] for the difference, -16% to -1%). Bacteremia occurred in 58 (22%) of 268 placebo-treated patients and in 38 (14%) of 268 penicillin-treated patients (P = .03; 95% CI for the difference, -14% to -1%), primarily due to a reduction in streptococcal bacteremic episodes that occurred in 14 penicillin-treated patients (5%) and in 27 placebo-treated patients (10%) (P = .05; 95% CI for the difference, -9% to -0.3%). Gram-negative rod bacteremias occurred in only two patients (1%) and in five patients (2%), respectively. Logistic regression analysis also supported the treatment effect on the development of bacteremia.\n These results demonstrate that the addition of penicillin V to fluoroquinolone prophylaxis in granulocytopenic patients with cancer effectively reduces febrile episodes and the incidence of bacteremia, especially that due to streptococcal species.",
"One hundred and eighty nine patients with primary biliary cirrhosis were entered into a double blind, placebo controlled randomised trial starting in January 1978 to assess the therapeutic value of d-penicillamine 1200 mg daily. Eighteen of the 98 patients receiving d-penicillamine and 22 of the 91 placebo treated patients died during the study. Thirty six per cent of those on d-penicillamine and 8% of those on placebo were withdrawn from the study. No difference in overall survival was noted between the two groups of patients whether the results were analysed for the entire period of observation or only during the period in which the patients were receiving therapy. The mortality rate of those receiving d-penicillamine in histological stage I to II, however, was one third of that of the placebo group although this difference did not reach statistical significance. Using the occurrence rate ratio as the statistical method of analysis, no effect of d-penicillamine was noted on any clinical, biochemical or histological features examined, except the serum alanine aminotransferase activity which was greater in those on active treatment. In this trial we have been unable to establish any therapeutic benefit from the drug."
] |
We conclude that further randomized, placebo-controlled, double-blind trials should be carried out to compare cyclosporine, azathioprine and benzathine-penicillin versus placebo in order to make the results generalizable and comparable.
|
CD006593
|
[
"15228994",
"15343260",
"15284736",
"9070140"
] |
[
"Biophysical profile with amniotic fluid volume assessments.",
"Amniotic fluid index vs single deepest pocket technique during modified biophysical profile: a randomized clinical trial.",
"A randomized clinical trial of the intrapartum assessment of amniotic fluid volume: amniotic fluid index versus the single deepest pocket technique.",
"A randomised comparison between amniotic fluid index and maximum pool depth in the monitoring of post-term pregnancy."
] |
[
"To compare the amniotic fluid index (AFI) with the single deepest pocket technique along with the other components of the biophysical profile (BPP) in predicting an adverse pregnancy outcome.\n Prospective, randomized trial of amniotic fluid assessment by AFI or single deepest pocket during a BPP. Cesarean delivery for fetal distress was the primary outcome evaluated.\n The AFI was used in 273 pregnancies and the single deepest pocket in 264. The AFI significantly increased the number of pregnancies labeled as oligohydramnios, 102 women (38%) compared with 46 women (17%; P <.001), odds ratio (OR) = 2.84, 95% confidence interval 1.90-4.25 in the single deepest pocket group. There was no difference in the number of women with oligohydramnios in the AFI group, 16 of 102 (16%), undergoing a cesarean delivery for fetal intolerance of labor compared with the single deepest pocket group, 6 of 46 (13%; P =.676). More women with normal fluid by the AFI method (AFI > 5), 20 of 170 (12%), underwent a cesarean delivery for fetal distress than the women with normal fluid by the single deepest pocket technique (2 cm x 1 cm pocket present) group, 12 of 218 (6%; P =.037, OR = 2.22, 95% confidence interval 1.05-4.70).\n The AFI offers no advantage in detecting adverse outcomes compared with the single deepest pocket when performed with the BPP. The AFI may cause more interventions by labeling twice as many at-risk pregnancies as having oligohydramnios than with the single deepest pocket technique.",
"The purpose of this study was to determine the superior technique, if either, of the amniotic fluid index (AFI) vs the single deepest pocket technique in predicting an adverse pregnancy outcome among high-risk patients undergoing antenatal testing.\n Patients having modified biophysical profile (nonstress test plus sonographic estimation of amniotic fluid) were randomized to either have AFI or determination of the presence or absence of a 2 x 1-cm single deepest pocket.\n Between January of 1997 and December of 2001, 1080 women were randomized with 530 women in the AFI arm, and 558 in the 2 x 1 pocket arm. The maternal demographics and prenatal complications were similar between groups. Significantly more patients were identified as having oligohydramnios using AFI (17%) compared with using 2 x 1 pocket (10%) ( P =.002). The overall rate of cesarean section for nonreassuring fetal heart rate (FHR) tracing was 3.8% (30 cases, with 16 cases in the AFI-monitored, and 14 cases in the 2 x 1 pocket-monitored groups, respectively, P =.608). Logistic regression analysis showed no difference between the groups with respect to the ability to identify patients who underwent cesarean section for nonreassuring FHR tracing during labor ( P =.999). The umbilical artery pH <7.1 ( P =.688) and admission to the newborn intensive care unit were also comparable between groups.\n During antepartum fetal surveillance, use of single deepest pocket compared with amniotic fluid index is associated with a significantly lower rate of suspected oligohydramnios.",
"The purpose of this study was to determine whether an intrapartum assessment of amniotic fluid identifies a pregnancy that is at risk for an adverse outcome.\n Parturients who were admitted for delivery were assigned randomly to have the amniotic fluid assessed either by amniotic fluid index or by the presence of a 2 x 1 pocket.\n The amniotic fluid index was obtained in 499 pregnancies, and the 2 x 1 technique was performed in 501. Oligohydramnios was diagnosed in 25% of amniotic fluid index pregnancies versus 8% with the use of the 2 x 1 pocket technique (P <.001). Both techniques failed to identify patients who underwent an amnioinfusion for fetal distress (P=.864) or who experienced variable (P=.208) or late decelerations (P=.210) that influenced delivery, fetal distress in labor (P=.220), caesarean delivery for fetal distress (P=.133), and admission to neonatal intensive care unit (P=.686).\n Neither the amniotic fluid index nor the 2 x 1 pocket technique that was undertaken as a fetal admission test identifies a pregnancy that is at risk for an adverse outcome.",
"To compare the impact of two different ultrasound methods for assessing amniotic fluid volume on the incidence of obstetric interventions in post-term pregnancies.\n A prospective randomised controlled trial.\n Liverpool Women's Hospital.\n Five hundred women with singleton, uncomplicated pregnancies with gestational age > or = 290 days.\n Random allocation to fetal monitoring by either: 1. amniotic fluid index and computerised cardiotocography, or 2. maximum pool depth and computerised cardiotocography.\n Primary: caesarean section. Secondary: the number of abnormal monitoring tests, induction of labour, intrapartum management and neonatal outcome.\n The number of abnormal amniotic fluid indices was significantly higher than the number of abnormal maximum pool depths (10% vs 2.4%; OR 4.51, 95% CI 1.82-11.21; P = 0.0008) which resulted in more inductions for abnormal post-term monitoring in the amniotic fluid index group (14.8% vs 8.4%; OR 1.89; 95% CI 1.07-3.33; P = 0.0362) and more intrapartum electronic fetal monitoring (94.4% vs 88.4%; OR 2.21; 95% CI 1.13-4.29; P = 0.0255). There were no other statistically significant differences in outcomes related to labour and delivery, but there was a trend towards more caesarean sections in the amniotic fluid index group (18.8% vs 13.2%), in particular caesarean sections for fetal distress (8% vs 4%). There were no perinatal deaths and no statistically significant differences in perinatal outcome between the two groups.\n Published reference ranges for amniotic fluid index overestimate the number of abnormal results in post-term pregnancies. Their use, when compared with maximum pool depth, is likely to increase the number of obstetric interventions with, as yet, an uncertain impact on perinatal mortality and morbidity. It is possible that antepartum fetal assessment in pregnancies where the risk of adverse perinatal outcome is very low may cause, rather than prevent morbidity."
] |
The single deepest vertical pocket measurement in the assessment of amniotic fluid volume during fetal surveillance seems a better choice since the use of the amniotic fluid index increases the rate of diagnosis of oligohydramnios and the rate of induction of labor without improvement in peripartum outcomes. A systematic review of the diagnostic accuracy of both methods in detecting decreased amniotic fluid volume is required.
|
CD003039
|
[
"11136839",
"10815320",
"9615797",
"9060560",
"7540696",
"9531581",
"15235901",
"9187068",
"1381626",
"10673519",
"8605328",
"8636779"
] |
[
"Granulocyte colony-stimulating factor in the treatment of high-risk febrile neutropenia: a multicenter randomized trial.",
"[Granulocyte colony-stimulating factor in the treatment of febrile neutropenia].",
"GM-CSF in chemotherapy-induced febrile neutropenia--a double-blind randomized study.",
"Granulocyte colony-stimulating factor in established febrile neutropenia: a randomized study of pediatric patients.",
"Improving treatment of chemotherapy-induced neutropenic fever by administration of colony-stimulating factors.",
"A placebo-controlled study of recombinant human granulocyte-macrophage colony-stimulating factor administered during and after induction treatment for de novo acute myelogenous leukemia in elderly patients. Groupe Ouest Est Leucémies Aiguës Myéloblastiques (GOELAM).",
"A prospective randomised evaluation of G-CSF or G-CSF plus oral antibiotics in chemotherapy-treated patients at high risk of developing febrile neutropenia.",
"Human granulocyte colony-stimulating factor after induction chemotherapy in children with acute lymphoblastic leukemia.",
"Granulocyte colony-stimulating factor to prevent dose-limiting neutropenia in non-Hodgkin's lymphoma: a randomized controlled trial.",
"Granulocyte colony-stimulating factor after intensive consolidation chemotherapy in acute myeloid leukemia: results of a randomized trial of the Groupe Ouest-Est Leucémies Aigues Myeloblastiques.",
"A randomized phase-III study of the efficacy of granulocyte colony-stimulating factor in children with high-risk acute lymphoblastic leukemia. Berlin-Frankfurt-Münster Study Group.",
"Randomized placebo-controlled trial of granulocyte-macrophage colony-stimulating factor in patients with chemotherapy-related febrile neutropenia."
] |
[
"Granulocyte colony-stimulating factors (G-CSFs) have been shown to help prevent febrile neutropenia in certain subgroups of cancer patients undergoing chemotherapy, but their role in treating febrile neutropenia is controversial. The purpose of our study was to evaluate-in a prospective multicenter randomized clinical trial-the efficacy of adding G-CSF to broad-spectrum antibiotic treatment of patients with solid tumors and high-risk febrile neutropenia.\n A total of 210 patients with solid tumors treated with conventional-dose chemotherapy who presented with fever and grade IV neutropenia were considered to be eligible for the trial. They met at least one of the following high-risk criteria: profound neutropenia (absolute neutrophil count <100/mm(3)), short latency from previous chemotherapy cycle (<10 days), sepsis or clinically documented infection at presentation, severe comorbidity, performance status of 3-4 (Eastern Cooperative Oncology Group scale), or prior inpatient status. Eligible patients were randomly assigned to receive the antibiotics ceftazidime and amikacin, with or without G-CSF (5 microg/kg per day). The primary study end point was the duration of hospitalization. All P values were two-sided.\n Patients randomly assigned to receive G-CSF had a significantly shorter duration of grade IV neutropenia (median, 2 days versus 3 days; P = 0.0004), antibiotic therapy (median, 5 days versus 6 days; P = 0.013), and hospital stay (median, 5 days versus 7 days; P = 0.015) than patients in the control arm. The incidence of serious medical complications not present at the initial clinical evaluation was 10% in the G-CSF group and 17% in the control group (P = 0.12), including five deaths in each study arm. The median cost of hospital stay and the median overall cost per patient admission were reduced by 17% (P = 0.01) and by 11% (P = 0.07), respectively, in the G-CSF arm compared with the control arm.\n Adding G-CSF to antibiotic therapy shortens the duration of neutropenia, reduces the duration of antibiotic therapy and hospitalization, and decreases hospital costs in patients with high-risk febrile neutropenia.",
"To determine whether granulocyte colony-stimulating factor (G-CSF) used in addition to antibiotic therapy, in patients with chemotherapy-induced febrile neutropenia shortens the period of fever, neutropenia and hospitalization.\n The study was prospective. Patients with lymphoblastic acute leukemia (LAL) were included. They received intensive chemotherapy of induction, intensification, or consolidation. At random, a group received amikacin-ceftriaxone; if no had response after 3 days, we added vancomicin and, after 7 days, amphotericin. The other group received in addition these antibiotics, granulocyte colony-stimulating factor.\n The groups were comparable in the magnitude of the initial neutropenia (< 0.5 x 10(9)/L), site of the infection, chemotherapy received germs isolated, age, and sex. The patients of the group that received FEC-G were cured in the course of 3.1 days; in the group without FEC-G, this occurred in 7.2 days (p = 0.0001). At the end of the infectious episode, the number of neutrophils, in the group with FEC-G, was of 1.9 x 10(9)/L versus 0.7 x 10(9)/L (p = 0.0009). The mortality was of one and two cases (p = 0.46). The global mortality was 7.5%.\n The addition of FEC-G to the treatment with antibiotics, in febrile neutropenia, decreases duration of days with fever, hospitalization and neutropenia. However, the frequency of cure is not augmented.",
"Modern chemotherapy programmes render patients susceptible to bacterial and fungal infections, and the risk of developing febrile neutropenia after a chemotherapy course is in proportion to the severity and duration of the neutropenia thus caused. This double-blind randomized study presents details of 29 patients who developed febrile neutropenia an average of 10 days after their course of chemotherapy for different types and stages of malignancy. Fourteen received granulocyte/macrophage colony stimulating factor (GM-CSF) and 15 placebo during 7 consecutive days as subcutaneous injections. The GM-CSF group demonstrated significant increases in total white blood cell count (TWBC) and absolute neutrophil count (ANC) from the morning of the third day of the study. The study concludes that GM-CSF has an important therapeutic role in the treatment of febrile neutropenia that arises during intensive chemotherapy programmes but further studies of dosage and therapy duration are required, as is the development of methods of assessing bone marrow vitality.",
"Infection in neutropenic patients is potentially life-threatening and carries important implications for hospital resource use. Prophylactic administration of cytokines may reduce the severity of neutropenia, but involves the treatment of all patients for the possible benefit of a minority. This study evaluates whether treatment with cytokines in the setting of established febrile neutropenia will influence outcome and be potentially more cost-effective.\n In a double-blind study, pediatric patients with fever and severe neutropenia were randomized to receive granulocyte colony-stimulating factor ([G-CSF] filgrastim; 5 microg/kg/d) or placebo, in addition to antibiotics. The study protocol required a resolution of fever and a neutrophil count > or = 0.2 x 10(9)/L for hospital discharge. Patients could be randomized for up to four independent febrile episodes. A total of 186 episodes of febrile neutropenia were investigated.\n Patients randomized to G-CSF had a shorter hospital stay (median, 5 v 7 days; P = .04) and fewer days of antibiotic use (median, 5 v 6 days; P = .02). G-CSF-treated patients also had more rapid neutrophil recovery and higher neutrophil levels at discharge. The 2-day reduction in hospital stay reduced the median bed cost by 29% per patient admission (P = .04).\n Under the clinical guidelines of our institution, the use of G-CSF in the treatment of established febrile neutropenia produced a small but significant reduction in the time that children required antibiotics and hospital admission, with possible cost savings.",
"Several randomized trials have tested the use of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in relieving chemotherapy-induced bone marrow suppression. However, the use of CSFs in the treatment of neutropenic fever remains virtually unexplored.\n This study evaluated the benefits of adding CSF therapy to the standard antibiotic treatments given to cancer patients for chemotherapy-induced neutropenic fever. The usefulness of CSFs was quantified in terms of reducing the following: (a) the duration of neutropenia, (b) the length of hospitalization, and (c) the overall cost of the treatment.\n A randomized trial was conducted to test whether the administration of either G-CSF or GM-CSF improved the outcome of standard antibiotic therapy (ceftazidime plus amikacin) in nonleukemic cancer patients with fever (> 38 degrees C) and grade IV neutropenia (absolute neutrophil count [ANC] < 500/mm3) induced by standard-dose chemotherapy. Of 121 patients who entered the trial, 39 received G-CSF (5 micrograms/kg body weight per day), 39 received GM-CSF (5 micrograms/kg body weight per day), and 43 received a placebo beginning just after the first dose of antibiotics. Treatments were continued for at least 5 days (7 days with clinically or microbiologically documented infections) or until 2 days after fever subsided and ANCs rose above 1000/mm3.\n The median duration of grade IV neutropenia (ANC of < 500/mm3) was 2 days in both CSF arms and 3 days in the placebo arm (P < .001). The median duration of neutropenia with an ANC of less than 1000/mm3 was also significantly shorter in patients receiving G-CSF or GM-CSF (P < .001). The median duration of fever was similar in the three arms. The median hospital stay was 5 days (range, 5-14 days) in the G-CSF arm, 5 days (range, 5-10 days) in the GM-CSF arm, and 7 days (range, 5-34 days) in the placebo arm (P < .001). The median time on CSF was 4 days in both treatment arms. The mean cost of overall treatment was reduced by $1300-$1400 in the CSF arms compared with the placebo arm (P = .11 for G-CSF versus placebo; P = .06 for GM-CSF versus placebo; P = .7 for G-CSF versus GM-CSF).\n Adding G-CSF or GM-CSF therapy to antibiotic treatment shortens the duration of neutropenia and the duration of hospitalization in patients with neutropenic fever. A statistically nonsignificant trend toward lower cost was observed in the CSF arms as compared with the placebo arm.\n The benefits of CSFs to cancer patients with chemotherapy-induced neutropenic fever merit further evaluation in large randomized trials.",
"The complete remission (CR) rate after intensive chemotherapy for acute myelogenous leukemia (AML) remains low in elderly patients, mainly because of a higher infectious mortality rate related to neutropenia and an increased incidence of adverse prognostic factors. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to potentially recruit leukemic blasts into cell cycle and improve cytotoxic effects when given during chemotherapy, and to shorten the duration of neutropenia when administered after chemotherapy. Two hundred forty patients aged 55 to 75 years who had newly diagnosed AML were randomly assigned to receive placebo or Escherichia coli-derived GM-CSF (5 micrograms/kg/d by 6-hour intravenous infusion) starting during induction chemotherapy on day 1 and continued through and after chemotherapy until recovery of neutrophils, or evidence of regrowth of leukemia, or up to day 28. Induction chemotherapy consisted of idarubicin (8 mg/m2/d on days 1 to 5) and cytarabine (100 mg/m2/d on days 1 to 7). The study drug was not administered subsequent to the induction course. Patients who achieved a CR received continuous maintenance therapy for 1 year with four quarterly reinduction courses; in the 55- to 64-year age subgroup, patients were randomly assigned to receive or not a consolidation course before maintenance therapy. The CR rate was similar in the GM-CSF and placebo groups (63% and 60.5%, respectively; P = .79). The mortality, rate of resistant disease, and rate of regrowth of leukemia were also similar in both groups. The time to neutrophil recovery was shorter in patients who received GM-CSF (24 v 29 days; P = .0001), but the incidence and characteristics of infectious events were not different. The 2-year disease-free survival (DFS) rate was significantly improved in the GM-CSF group (48% v 21% in the placebo group; P = .003). This effect was highly significant in the cohort of patients aged 55 to 64, but only marginal in patients >/=65 years of age. There was a trend toward a longer overall survival (OS) in the GM-CSF group (P = .082). In summary, the administration of GM-CSF, concomitantly with chemotherapy and thereafter during induction course in AML, shortened the time to neutrophil recovery, but did not improve the CR rate in patients aged 55 to 75. Nonetheless, DFS and OS were significantly prolonged in patients aged 55 to 64 treated with GM-CSF. These results are promising and further evaluation of myeloid growth factors in AML is warranted.",
"Febrile neutropenia (FN) remains a major dose-limiting complication among patients treated with chemotherapy. Haematopoietic colony stimulating factors (G-CSF and GM-CSF) made possible a significant improvement in the management of FN, both in the therapeutic and in the prophylactic approach. The use of antibiotic prophylaxis also permits a definite reduction of severe infections during neutropenia. Nevertheless, the possible role of these two interventions for secondary prevention of FN is still unclear.\n We conducted a prospective randomised trial by comparing the efficacy of granulocyte-colony stimulating factor (G-CSF) and the association of G-CSF with oral antibiotics in the secondary prevention of FN. We included in our study those patients who, after an episode of FN, continued to be treated with the same chemotherapy without reduction of dose intensity. They were randomised into two groups: the first received G-CSF (group G; filgrastim, 5 microg/kg day), and the second was treated with an association of G-CSF and amoxicillin/clavulanate plus ciprofloxacin (group G/ACC).\n Forty-eight patients were randomised (group G: n=23 and group G/ACC: n=25). There was no recurrence of FN among the patients receiving G-CSF and only one episode in the combined therapy group (p=1). With regard to the side effects, there was no significant difference in the two groups.\n The use of G-CSF for the secondary prevention of FN is extremely effective and allows the maintenance of chemotherapy dose intensity. Our study showed that the addition of antibiotics does not seem to be required.",
"Recombinant human granulocyte colony-stimulating factor PO1 CA-20180ilgrastim) hastens the recovery from neutropenia after P30 CA-21765emotherapy, but its role in the management of childhood leukemia is unclear.\n We randomly assigned 164 patients with acute lymphoblastic leukemia (age range, 2 months to 17 years) to receive placebo or G-CSF (10 microg per kilogram of body weight per day subcutaneously), beginning one day after the completion of remission-induction therapy and continuing until the neutrophil count was greater than or equal to 1000 per cubic millimeter for two days. The clinical and laboratory effects of this therapy were documented for 21 days. The area under the plasma G-CSF concentration-time curve was measured on days 1 and 7 in both groups.\n Responses to the growth factor could be assessed in 148 patients (73 in the G-CSF group and 75 in the placebo group). G-CSF treatment did not significantly lower the rate of hospitalization for febrile neutropenia (58 percent in the G-CSF group vs. 68 percent in the placebo group; relative risk, 0.85; 95 percent confidence interval, 0.59 to 1.16), increase the likelihood of event-free survival at three years (83 percent in both groups), or decrease the number of severe infections (five in the G-CSF group vs. six in the placebo group). Patients treated with G-CSF had shorter median hospital stays (6 days vs. 10 days, P=0.011) and fewer documented infections (12 vs. 27, P=0.009). The median total costs of supportive care were similar in the G-CSF and placebo groups ($8,768 and $8,616, respectively). Among patients who did not have febrile neutropenia during the first week of G-CSF or placebo injections, higher systemic exposure to the growth factor on day 7 was significantly related to a lower probability of subsequent hospitalization (P=0.049).\n G-CSF treatment had some clinical benefit in children who received induction chemotherapy for acute lymphoblastic leukemia, but it did not reduce the rate of hospitalization for febrile neutropenia, prolong survival, or reduce the cost of supportive care.",
"The effect of granulocyte colony-stimulating factor (G-CSF) on neutropenia, infection, and cytotoxic chemotherapy administration was studied in a randomized trial in patients receiving intensive weekly chemotherapy for non-Hodgkin's lymphoma (NHL). Eighty patients (aged 16 to 71 years) with high-grade NHL (Kiel) of any stage were randomized to receive VAPEC-B chemotherapy alone (39 patients) or with G-CSF administered as a daily subcutaneous dose of 230 micrograms/m2 (41 patients). Prophylactic ketoconazole and cotrimoxazole were administered to all patients throughout treatment. The protocol specified identical dose modification and antibiotic treatment criteria bor both groups. Neutropenia (absolute neutrophil count [ANC] less than 1.0 x 10(9)/L) occurred in 15 of 41 (37%) of the G-CSF-treated patients and in 33 of 39 (85%) of the controls, giving a relative risk for control patients of 2.31 (95% confidence interval [CI], [1.51, 3.54]; P = .00001). Fever (greater than or equal to 37.5 degrees C) with neutropenia (ANC less than 1.0 x 10(9)/L) occurred in 9 of 41 (22%) of the G-CSF group and in 17 of 39 (44%) of the controls (relative risk for control, 2.26; 95% CI [1.01, 5.06]; P = .04). There were fewer treatment delays, with shorter duration (P = .01) in patients receiving G-CSF. Chemotherapy doses were reduced in 4 of 41 (10%) of the G-CSF patients and 13 of 39 (33%) of the controls (P = .01). The dose intensity of cytotoxic chemotherapy was significantly increased in patients receiving G-CSF (median of 95% in G-CSF group compared with 83% in control patients). Three vascular deaths occurred in the G-CSF group. Delays in the control group most commonly resulted from neutropenia (19 patients, compared with 2 patients in the G-CSF-treated group, P = .000007). Severe mucositis was the major dose-limiting toxicity in G-CSF-treated patients, but did not occur more frequently than in controls (15 patients in each group). Overall, patients randomized to receive G-CSF achieved a greater dose intensity than control patients, but this did not result in significant differences in drug toxicity (other than neutropenia), intravenous antibiotic usage, or hospitalization between the two groups.",
"Ten years after the first clinical studies, the clinical impact of myeloid growth factors in acute myeloid leukemia is still unclear. One of the objectives of the Groupe Ouest-Est Leucémies Aigues Myeloblastiques (GOELAM) 2 trial was to evaluate the benefit of granulocyte colony-stimulating factor (GCSF) given only after the two courses of intensive consolidation chemotherapy (ICC) used to maintain complete remission (CR).\n One hundred ninety-four patients who were in CR after induction treatment were randomly assigned to receive G-CSF (100 patients) or no G-CSF (94 patients) after two courses of ICC (ICC 1, high-dose cytarabine plus mitoxantrone; ICC 2, amsacrine plus etoposide). G-CSF (filgrastim) was administered from the day after chemotherapy until granulocyte recovery at a daily dose of 5 microg/kg.\n In the G-CSF group, the median duration of neutropenia (< 0.5 x 10(9)/L) was dramatically reduced, both after ICC 1 (12 v 19 days, P <.001) and after ICC 2 (20 v 28 days, P <.001). The median duration of hospitalization was also significantly shorter in the G-CSF group (24 v 27 days after ICC 1, P <.001; 29 v 34 days after ICC 2, P <. 001). The median duration of intravenous antibiotics was significantly reduced after ICC 1 and ICC 2, and the median duration of antifungal therapy was significantly reduced after ICC 1. However, the incidence of microbiologically documented infections, the toxic death rate, the 2-year disease-free survival, and the 2-year overall survival were not affected by G-CSF administration. Moreover, the median interval between ICC1 and ICC2 was reduced by only 2 days, and the number of patients undergoing ICC2 was not increased in the G-CSF arm.\n G-CSF should be administered routinely after ICC to reduce the duration of neutropenia and hospitalization. However, G-CSF did not seem to significantly increase the feasibility of this two-course program or modify overall outcome.",
"Overall chemotherapeutic treatment results in pediatric acute lymphoblastic leukemia (ALL) are good, with event-free survival (EFS) rates over 70%. However, for a subset of patients characterized by high-risk (HR) features the outcome is less favorable, with EFS rates below 50%. Intensification of chemotherapy may improve the outcome for those patients, but increased toxicity, particularly myelosuppression, limits the escalation of dose intensity. Recombinant methionyl human granulocyte colony-stimulating factor (r-metHuG-CSF) is known to reduce myelosuppression after cancer chemotherapy in adults. The objective of this study was to examine the effect of r-metHuG-CSF on myelosuppression in HR pediatric ALL patients and on the overall response rate to chemotherapy. Patients with HR pediatric ALL were randomized to receive nine alternating cycles of chemotherapy according to the German ALL-Berlin-Frankfurt-Münster 90 protocol either alone or followed by r-metHuG-CSF administered prophylactically at a dose of 5 microg/kg/d subcutaneously. In both groups, the planned interval between chemotherapy courses was a minimum of 21 days. We report here interim results of 34 patients. The incidence of febrile neutropenia (absolute neutrophil count <0.5 x 10(9)/L and oral temperature > or = 38.5 degrees C) was 17% in children receiving r-metHuG-CSF, as compared with 40% in the control group (P = .007). In addition, the median total duration of febrile neutropenia was reduced from 20.3 to 6.2 days per patient (P = .02). Culture-confirmed infections occurred less frequently in the r-metHuG-CSF group (8% v 15%; P = .04), and the total duration of intravenous antibiotic use was significantly reduced from 32.2 days to 18.2 days per patient (P = .02). A tighter adherence to the planned treatment schedule was also facilitated by r-metHuG-CSF (P = .007). With a median follow-up of 3.3 years, the estimated EFS of 4 years is 41% +/- 12%. In conclusion, r-metHuG-CSF administered prophylactically in the interval between chemotherapy courses significantly reduced febrile neutropenia, culture-confirmed infections, and duration of intravenous antibiotic administration and allowed for tighter adherence to the treatment schedule.",
"To determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF) used in addition to standard inpatient antibiotic therapy shortens the period of hospitalization due to chemotherapy-induced neutropenic fever.\n One hundred thirty-four patients with a hematologic (n = 47) or solid tumor (n = 87) who had severe neutropenia (< 0.5 x 10(9)/L) and fever (> 38.5 degrees C once or > 38 degrees C twice over a 12-hour observation period) were randomly assigned to receive GM-CSF 5 micrograms/kg/d (n = 65) or placebo (n = 69) in conjunction with broad-spectrum antibiotics for a minimum of 4 days and a maximum of 14 days. GM-CSF/placebo and antibiotics were stopped if the neutrophil count was greater than 1.0 x 10(9)/L and temperature less than 37.5 degrees C during 2 consecutive days, or for a leukocyte count > or = 10 x 10(9)/L, both followed by a 24-hour observation period (hospitalization period).\n Compared with placebo, GM-CSF enhanced neutrophil recovery. Median neutrophil counts at day 4 were 2.5 x 10(9)/L (range, 0 to 25) in the GM-CSF arm and 1.3 x 10(9)/L (range, 0 to 9) in the placebo arm (P < .001). No significant difference was observed with regard to median number of days with less than 1.0 x 10(9)/L neutrophils (4 v 4) or days of fever (3 v 3). The median number of days patients were hospitalized while on study was comparable in the GM-CSF and placebo groups at 6 (range, 3 to 14) versus 7 (range, 4 to 14), respectively, according to an intention-to-treat analysis (P = .27). Quality-of-life scores in 90 patients demonstrated significant differences in favor of the placebo group. Hospital costs were significantly higher for GM-CSF-treated patients if GM-CSF was included in the price (median costs, $4,140 [US] for GM-CSF v $590 for placebo; P < .05).\n These results indicate that GM-CSF does not affect the number of days for resolution of fever or the hospitalization period for this patient group, although a significant effect of GM-CSF was observed on neutrophil recovery."
] |
The use of CSF in patients with febrile neutropenia due to cancer chemotherapy does not affect overall mortality, but reduces the amount of time spent in hospital and the neutrophil recovery period. It was not clear whether CSF has an effect on infection-related mortality.
|
CD003428
|
[
"9438143",
"2019162",
"10919682",
"11389575",
"9033441",
"10208190",
"8610720",
"10077140",
"9227720",
"2971565",
"11316640",
"7597661",
"10069876"
] |
[
"Long-term effects of formoterol and salbutamol on bronchial hyperreactivity and beta-adrenoceptor density on lymphocytes in children with bronchial asthma.",
"A controlled trial of long-term bronchodilator therapy in cystic fibrosis.",
"Equivalence of salbutamol 200 microg four times daily propelled by propellants 11 and 12 or HFA 134a in mild to moderate asthmatics. Eastern European study group.",
"Bronchodilatory effects of salbutamol, ipratropium bromide, and their combination: double-blind, placebo-controlled crossover study in cystic fibrosis.",
"Short-term regular beta 2-adrenergic agonists treatment is safe in mild asthmatics taking low doses of inhaled steroids.",
"Safety of long-term treatment with HFA albuterol.",
"Results of a multicenter study of nebulized inhalant bronchodilator solutions.",
"Switching patients with asthma from chlorofluorocarbon (CFC) albuterol to hydrofluoroalkane-134a (HFA) albuterol.",
"Effects of the long acting beta agonist formoterol on asthma control in asthmatic patients using inhaled corticosteroids. The Netherlands and Canadian Formoterol Study Investigators.",
"Effect of three different bronchodilators during an exacerbation of chronic obstructive pulmonary disease.",
"Use of a long-acting inhaled beta2-adrenergic agonist, salmeterol xinafoate, in patients with chronic obstructive pulmonary disease.",
"Subsensitivity of bronchodilator and systemic beta 2 adrenoceptor responses after regular twice daily treatment with eformoterol dry powder in asthmatic patients.",
"Sustained bronchoprotection, bronchodilatation, and symptom control during regular formoterol use in asthma of moderate or greater severity. The Canadian FO/OD1 Study Group."
] |
[
"Long-term treatment with short-acting beta 2-sympathomimetic drugs has recently been suggested to be due to a rise in asthma mortality. This effect has been attributed to an increase in bronchial hyperreactivity, a desensitization of beta 2-adrenoceptors and/or a rebound effect after cessation of the therapy. Formoterol, a new long-acting beta 2-symathomimetic drug, has been reported to possess not only bronchodilatation but also antiinflammatory effects. The aim of the present study was to investigate whether long-term effects of salbutamol and/or formoterol could deteriorate asthma management. Therefore, in a trial lasting 90 days, we evaluated the effects of the two drugs on lung function, on the protection they provided against inhalative provocation with histamine, and on tachyphylaxis as monitored by the beta-adrenergic density on mononuclear leukocytes (MNL). Two groups of 11 children each with stable asthma were treated with daily doses of either 4 x 200 micrograms salbutamol or 2 x 24 micrograms formoterol in monotherapy. The lung function was measured six times during the trial period, on day 1, and on day 90, before and after inhaling the drug and at all investigations both with and without histamine provocation. In both groups, the bronchodilatory effect of either formoterol or salbutamol remained constant. The lung function values before and after drug inhalation (specific airway resistance sRAW, forced expiration volume FEV1, vital capacity VC) did not alter significantly. After histamine provocation, the protection was more pronounced in the formoterol group. No changes in the beta-adrenoceptor density on MNL and no significant side effects were seen throughout the trial period. We therefore conclude that formoterol protects significantly better against the bronchial challenge with histamine than does salbutamol. Both drugs did not deteriorate the lung function in asthmatic children. In addition, there was no evidence that long-term treatment leads to a desensitization of beta 2-sympathomimetic effects.",
"To evaluate the effect of long-term bronchodilator therapy in CF patients with demonstrated bronchial hyperresponsiveness, we first performed methacholine challenges to determine responsiveness, then entered 27 patients (16 methacholine responders and 11 nonresponders) into a two-month double-blind crossover trial of albuterol, 90 micrograms by inhalation four times a day vs placebo. Among the responders, daily PEFR measures improved significantly more during treatment with albuterol (12 +/- 32 L/min) than with placebo (-0.4 +/- 19 L/min; p less than 0.05). In addition, a clinically important level of improvement in PEFR (15 percent increase) was reached significantly more frequently in the responders. Methacholine nonresponders had no change in PEFR on either albuterol or placebo. Daily symptom scores as well as spirometry measurements at biweekly visits did not show significant changes. We conclude that long-term therapy with inhaled albuterol improves lung function in CF patients, but only in those with bronchial hyperresponsiveness as demonstrated by methacholine challenge.",
"The phasing out of chlorofluorocarbons (CFCs) requires the development of an alternative non-ozone depleting propellant for use in pressurized metered dose inhalers (pMDIs). The present study assessed the effects on tolerability and efficacy of a switch from the currently available formulation containing the CFC propellants 11 and 12 to an alternative non-CFC formulation using the propellant hydrofluoroalkane (HFA) 134a in patients with mild to moderate asthma. After a 4-week run-in period during which patients received salbutamol 200 microg four times daily from a CFC pMDI, 547 patients were randomized to 12 weeks of treatment with salbutamol 200 microg four times daily administered from either an HFA 134a pMDI (Ventolin CFC-free; 277 patients) or CFC pMDI (Ventolin, 270 patients). At the end of this period, all patients then received a further 4 weeks of treatment with the same dose of salbutamol via a CFC pMDI (run-out period). On the basis that high doses of beta2-agonists are known to increase heart rate, change in heart rate was selected as the primary outcome variable. Small increases in heart rate were observed during the treatment period and these changes were comparable in both groups; the 90% confidence interval for the treatment differences was within the predefined limits for clinical equivalence (+/- 10 beats min(-1)). The incidence of adverse events was similar in both groups and there were no reports of paradoxical bronchospasm. Furthermore, daily PEF measurements showed comparability in terms of lung function. Symptom scores and use of additional bronchodilator were also similar in both groups. These results demonstrate that salbutamol (800 microg day(-1)), formulated with HFA 134a is equivalent to the current CFC formulation in terms of tolerability and efficacy.",
"The efficacy of inhaled sympathomimetic and anticholinergic agents on airway obstruction in cystic fibrosis (CF) has been proven in several studies. However, studies comparing combined therapy with monotherapy led to divergent results, probably due to different study designs, different dosages, and the small numbers of patients investigated. Therefore, we wanted to answer the question which inhalation has the best short term effect: a sympathomimetic or an anticholinergic agent, or the combination of both. We investigated 17 patients with CF on 4 successive days in the morning, using pulmonary function testing before and 30 min after inhalation. Each patient received aerosolized salbutamol (SB, maximum dose (max.) 2.5 mg), ipratropium bromide (IB, max. 0.5 mg), the combination of both, or placebo (normal saline) in a randomized, double-blind crossover design. The mean forced expiratory volume in the first second improved significantly (adjusted P-value < 0.017) after each treatment compared to placebo. Analysis of variance showed that SB and combination therapy with SB and IB were superior to IB alone, without significant difference between SB and combination therapy. Response of a patient to combined therapy was usually associated with response to SB. Long-term efficacy and side effects of treatment with bronchodilators still remain to be investigated after this short term study. We conclude that in CF patients bronchodilator therapy with sympathomimetic agents is usually sufficient. Only in cases with proven additional benefit from inhalation by anticholinergics should combination therapy be recommended.",
"Regular treatment with beta 2-adrenergic agonists is controversial in bronchial asthma. To investigate whether beta 2-adrenergic agonists can be used safely if associated with low doses of inhaled steroids, for a short period, without a deterioration of asthma control, we have examined 24 mild asthmatics. In a parallel, double-blind, placebo-controlled study, 1 week of run-in and run-out period framed 3 weeks of treatment. All patients received inhaled beclomethasone dipropionate (BDP 250 micrograms t.i.d.); after 1 week, 12 patients inhaled 400 micrograms of broxaterol and 12 patients received placebo t.i.d. FVC, FEV1, PD20-FEV1 methacholine, morning and evening PEF, and PEF amplitude % mean were measured before, during, and after treatment. No significant changes were noted in patients receiving inhaled broxaterol. There were no differences in symptoms and the use of rescue medication (salbutamol spray). We conclude that short-term regular treatment with beta 2-adrenergic agonists is not associated with a deterioration in asthma control in mild asthmatics inhaling low doses of steroids.",
"Chlorofluorocarbons (CFCs) used as propellants in metered-dose inhalers deplete stratospheric ozone, which results in serious public health concerns. Albuterol has been reformulated in the non-ozone-depleting propellant, hydrofluoroalkane-134a (HFA albuterol).\n The primary objective was to compare the safety of HFA albuterol to an albuterol product formulated in chlorofluorocarbon propellants (CFC albuterol) during 1 year of treatment in asthmatics. Bronchodilator efficacy of the two products was assessed as a secondary objective.\n The results from two open-label, parallel-group trials of similar design in asthmatics requiring short-acting beta-agonists for symptom control were combined. Patients took two puffs bid of either HFA albuterol or CFC albuterol for 1 year. Additional puffs of study drug were allowed as needed to control asthma symptoms. Adverse events were recorded at clinic visits. Patients self-administered study drug at quarterly visits and underwent serial spirometry during a 6-h period postdose. Bronchodilator efficacy variables, based on FEV1 response to study drug, were proportion of responders, time to onset of effect, peak percent change, time to peak effect, duration of effect, and area under the curve. Differences between products and changes over time in efficacy variables were assessed using an analysis of variance model. Regression analyses with FEV1 as a covariate were performed post-hoc to analyze changes in bronchodilator efficacy over time.\n Demographic and baseline characteristics were similar for patients receiving HFA albuterol (n = 337) and CFC albuterol (n = 132). Total reported adverse events were similar for the two treatments. Differences in only four individual adverse events were noted: the HFA albuterol group reported more gastroenteritis and dizziness; the CFC albuterol group reported more epistaxis and expectoration. Adverse events attributed to study drug use were infrequent. No serious adverse events were related to study drug use. Predose FEV1 at quarterly visits increased to a small extent in both groups from month 0 to month 12. The bronchodilator efficacy of HFA albuterol was comparable to that of CFC albuterol at the quarterly visits, but decreased from baseline for both products over the 12 months of treatment. Use of inhaled corticosteroids, nasal corticosteroids, or theophylline did not explain the increase in predose FEV1 over time and did not protect patients from developing reduced bronchodilator efficacy by month 12. The change in predose FEV1 did not entirely account for the reduced bronchodilator efficacy over time.\n HFA albuterol has a safety profile similar to that of CFC albuterol during chronic, scheduled use, and both drugs are well tolerated. HFA albuterol and CFC albuterol provided comparable bronchodilator efficacy, but bronchodilator efficacy decreased for both products with 1 year of use.",
"The efficacy, persistence of bronchodilator action, and safety of the quaternary ammonium anticholinergic agent, ipratropium bromide (500 microgram), and placebo were compared when each was added in solution form to the beta-adrenergic agonist solution, metaproterenol sulfate (15 mg), and administered three times daily for 12 weeks to a total of 213 patients with chronic obstructive pulmonary disease (COPD). Subjects had a mean forced expiratory volume in 1 second (FEV1) of approximately 1 liter (37% of predicted) and were permitted to use nonanticholinergic therapy for COPD throughout the trial. The study was a randomized, double-blind, 85-day, parallel-group, eight-center study. On a 3 test days, 1, 43, and 85, mean peak responses for FEV1 and forced vital capacity and mean area under the curve were significantly higher for the iprathropium bromide-metaproterenol combination than for metaproterenol only. Duration of action was also significantly longer for the combination therapy than for the beta-agonist alone on test days 1 and 43. Neither treatment regimen produced an demonstrable effect on daily morning peak expiratory flow rates, reported respiratory symptoms, or quality of life. Both treatment regimens were similarly well tolerated with a comparable frequency of adverse events. These results suggest that the combination of iprathropium bromide and metaproterenol inhalation solutions offers a potential therapeutic advantage to patients with symptomatic COPD over nebulized metaproterenol alone without the risk of increased side effects.",
"Chlorofluorocarbon (CFC) propellants deplete stratospheric ozone. Production and use of CFCs, except for certain critical exemptions, has been prohibited by the Montreal Protocol. Use of CFCs as propellants in metered-dose inhalers (MDIs) is still allowed, but the U.S. Food and Drug Administration is planning the transition to alternative propellants for use in MDIs. Hydrofluoroalkane-134a (HFA), a non-ozone-depleting propellant, has been used to reformulate albuterol (HFA albuterol). This study evaluates whether comparable safety and efficacy continues for 12 weeks after patients with asthma are switched from CFC albuterol to HFA albuterol. Patients with asthma stabilized on CFC albuterol during a 12-week safety and efficacy trial were randomized to either continue receiving CFC albuterol or to be switched to receive HFA albuterol in a yearlong safety and efficacy trial. Safety and efficacy were compared over the first 12 weeks of the yearlong trial between patients who had remained on CFC albuterol and those who had been switched to HFA albuterol. Bronchodilator efficacy was evaluated by serial spirometry for 6 hr after the patients self-administered the study drug in the clinic. Safety was assessed by measuring changes in pulse rate, blood pressure, and electrocardiogram (ECG) intervals after dosing with study drug, monitoring adverse events, and performing prestudy and poststudy laboratory testing and physical examinations. No significant differences in bronchodilator efficacy between the patients continuing to receive CFC albuterol and those switched to HFA albuterol were found in the 12 weeks after the switch. No differences between the two products were found for changes in pulse rate, blood pressure, and ECG intervals. Adverse event profiles were similar for the two products, except the patients remaining on CFC albuterol reported increased asthma symptoms and rhinitis significantly more often than the patients switched to HFA albuterol. No clinically meaningful changes in laboratory tests or physical examinations were found in either treatment group. Patients with asthma switched from CFC albuterol to HFA albuterol receive comparable bronchodilation with a similar safety profile as those continuing to receive CFC albuterol.",
"The long acting beta 2 agonist formoterol has proved to be an effective bronchodilator with a prolonged action of 12-14 hours. However, the precise role of formoterol in the maintenance treatment of asthma is still under debate. A study was performed to investigate the efficacy and safety of treatment with formoterol for six months in subjects with asthma.\n In a multicentre double blind, placebo controlled, parallel group study 239 subjects with mild to moderate asthma were randomly assigned to treatment with either inhaled formoterol 24 micrograms twice daily (n = 125) or placebo (n = 114) during eight months. The study consisted of a four week run in period, a 24 week treatment period, and a four week washout period. All subjects were using regular inhaled corticosteroids (100-3200 micrograms daily) but were still needing at least five inhalations of short acting beta 2 agonist per week for symptom relief. The study was performed in 10 outpatient clinics in Canada, and five outpatient clinics and one coordinating centre for 44 Dutch general practitioners in The Netherlands. Twice daily self-reported peak expiratory flow (PEF) measurements, symptom scores, and rescue beta 2 agonist use during the last 28 treatment days compared with baseline values were used as main outcome measures. Spirometric values were measured at entry, at the start of treatment, after four, 12 and 24 weeks of treatment, and after four weeks washout.\n One hundred and twenty five subjects received formoterol 24 micrograms twice daily via Turbohaler and 114 received placebo. Baseline FEV1 was 67.1% predicted and mean bronchodilator reversibility was 26%. The mean total asthma symptom score was 3.6 (maximum possible 21). A significant decrease in symptoms in favour of formoterol (difference from placebo -0.64, 95% CI -0.04 to -1.23, p = 0.04) was observed. Compared with placebo, morning PEF increased (difference from placebo 28 l/min, 95% CI 18.3 to 37.7, p = 0.0001) and the use of short acting beta 1 agonists decreased (daytime difference from placebo -1.1 inhalation, 95% CI -1.4 to -0.7, p = 0.0001) in the formoterol group. PEF returned to baseline following discontinuation of formoterol, as did asthma symptom scores. Thirty three patients treated with formoterol and 32 treated with placebo required treatment with prednisolone during the study (58 and 55 courses, respectively).\n Adding formoterol 24 micrograms twice daily by Turbohaler to inhaled corticosteroids was effective in improving symptom scores and morning PEF, and decreasing the use of rescue beta 2 agonists. There was no apparent loss of asthma control during 24 weeks of treatment with formoterol.",
"This study evaluates the effect of three different bronchodilators (beta 2-adrenergic, anticholinergic and methylxanthine) alone and in randomized sequence, during an exacerbation in thirteen patients with chronic obstructive pulmonary disease. Dose-response curves were obtained for inhaled salbutamol and inhaled ipratropium bromide. The bronchodilator effect of a perfusion of aminophylline was also assessed. When a plateau of bronchodilatation was achieved with one agent, one dose of a second bronchodilator was administered to see whether additional bronchodilation could be achieved. The increments in FEV1 and FVC were similar with the three agents. The addition of a second bronchodilator did not result in significant increments in most of the patients. In at least half of the patients the doses of salbutamol and ipratropium that produced the maximal bronchodilatation were twice that currently employed.",
"Chronic obstructive pulmonary disease (COPD) is a condition in which continuous bronchodilation may have clinical advantages. This study evaluated salmeterol, a beta-agonist bronchodilator with a duration of action substantially longer than that of short-acting beta-agonists, compared with ipratropium, an anticholinergic bronchodilator, and placebo in patients with COPD. Four hundred and five patients with COPD received either salmeterol 42 microg twice daily, ipratropium bromide 36 microg four times daily, or placebo for 12 wk in this randomized, double-blind, parallel-group study. Patients were stratified on the basis of bronchodilator response to albuterol (> 12% and > 200-ml improvement) and were randomized within each stratum. Bronchodilator response was measured over 12 h four times during the treatment period. Salmeterol provided similar maximal bronchodilatation to ipratropium but had a longer duration of action and a more constant bronchodilatory effect with no evidence of bronchodilator tolerance. Both active treatments were well tolerated. Salmeterol was an effective bronchodilator with a consistent effect over this 12-wk study in patients with COPD, including those \"unresponsive\" to albuterol. The long duration of action of salmeterol offers the advantage of twice daily dosing compared with the required four times a day dosing with ipratropium.",
"There is controversy as to the role of long acting beta 2 agonists such as eformoterol and, in particular, whether bronchodilator tolerance occurs during continuous therapy. The purpose of this study was to extend previous observations of bronchodilator subsensitivity with metered dose eformoterol aerosol in order to assess whether tolerance also occurs with a dry powder formulation of the same drug.\n Sixteen asthmatic patients of mean age 33 (range 18-53) years and FEV1 (% predicted) of 64 (3)%, of whom 13 were receiving inhaled corticosteroids, received regular treatment with eformoterol 24 micrograms twice daily or placebo twice daily (without beta 2 agonists) given concurrently for four weeks in a randomised double blind cross-over design. An initial two week run-in was used when beta 2 agonists were withdrawn and substituted with ipratropium bromide. Dose-response curves to eformoterol (cumulative dose 6-102 micrograms) for airways and systemic beta 2 responses were constructed at the end of each treatment period.\n Baseline values for airways and systemic responses were similar. The peak delta FEV1 response from the dose-response curve (as change from baseline) and the delta response for FEV1 and FEF25-75 at six hours after the last dose were attenuated after eformoterol compared with placebo: peak delta FEV1 response 1.001 with placebo v 0.841 with eformoterol (95% CI 0.04 to 0.28); at six hours 0.931 with placebo v 0.581 with eformoterol (95% CI 0.20 to 0.50); and for delta FEF25-75 at six hours 1.29 1/s with placebo v 0.87 1/s with eformoterol (95% CI 0.15 to 0.69). Morning peak expiratory flow rate was significantly improved during treatment with eformoterol (451 1/min) compared with placebo (399 1/min) (95% CI 21 to 82). Systemic beta 2 responses were blunted after eformoterol, together with a reduction in lymphocyte beta 2 receptor binding density.\n Regular twice daily eformoterol dry powder may produce bronchodilator subsensitivity in terms of both peak and duration of response to cumulative repeated doses of eformoterol. Systemic beta 2-mediated adverse effects also showed tolerance, which was mirrored by downregulation of lymphocyte beta 2 adrenoceptors.",
"Recent studies have raised concern that regular inhalation of beta2 -agonists may cause a worsening of asthma control compared with on-demand dosing regimens.\n The objective of this study was to compare the effect of twice daily formoterol (Foradil), 4 times daily albuterol, and on-demand albuterol on bronchial hyperresponsiveness (BHR), lung function measurements, symptoms, and other indicators of disease control over 6 months inpatients with asthma of moderate or greater severity receiving concomitant inhaled corticosteroids. We also looked for occurrence of rebound BHR on discontinuation of treatment.\n This was a multicenter, parallel-group, double-blind, clinical trial. Methacholine PC20 was the primary outcome variable. Other outcome variables included symptom scores, use of rescue medication, morning peak expiratory flow (PEF), serial FEV1 measurements, and asthma exacerbations.\n Of the 271 randomized patients, 217 completed the study. Formoterol was significantly superior to on-demand albuterol with regard to methacholine PC20, FEV1, PEF, symptom scores, and use of rescue medication at each measured time point/interval. Regular albuterol was superior to on-demand albuterol with regard to PC20 and FEV1, but not PEF or various clinical scores. After a small drop in the magnitude of bronchoprotection and bronchodilatation occurring shortly after randomization, there was no evidence of progressive tolerance to either regular treatment for any of the measured variables or of rebound increase in BHR 2 days after the end of treatment. The formoterol group had the lowest number of exacerbation days, as defined by high intake of rescue bronchodilator and/or symptom scores, whereas the number of exacerbations requiring increased corticosteroid coverage was similar in the 3 groups.\n In patients with asthma of moderate or greater severity receiving inhaled corticosteroids, formoterol taken twice daily resulted in superior bronchoprotection, bronchodilatation, and clinical control compared with on-demand albuterol over 6 months. Four times daily albuterol was superior to on-demand albuterol for only some of the end points. Progressive tolerance and a rebound increase in BHR on discontinuation of beta-agonists were not found"
] |
It was not possible to determine fully the effectiveness of inhaled bronchodilators in CF as a meta-analysis was not possible. However, short and long-acting beta-2 agonists can be beneficial both in the short and long term in individuals with demonstrable bronchodilator responsiveness or bronchial hyper-responsiveness. As we found no evidence, the use of fenoterol, formoterol or tiotropium in CF cannot be supported.
|
CD006248
|
[
"10764420"
] |
[
"Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix."
] |
[
"To determine whether the addition of cisplatin-based chemotherapy (CT) to pelvic radiation therapy (RT) will improve the survival of early-stage, high-risk patients with cervical carcinoma.\n Patients with clinical stage IA(2), IB, and IIA carcinoma of the cervix, initially treated with radical hysterectomy and pelvic lymphadenectomy, and who had positive pelvic lymph nodes and/or positive margins and/or microscopic involvement of the parametrium were eligible for this study. Patients were randomized to receive RT or RT + CT. Patients in each group received 49.3 GY RT in 29 fractions to a standard pelvic field. Chemotherapy consisted of bolus cisplatin 70 mg/m(2) and a 96-hour infusion of fluorouracil 1,000 mg/m(2)/d every 3 weeks for four cycles, with the first and second cycles given concurrent to RT.\n Between 1991 and 1996, 268 patients were entered onto the study. Two hundred forty-three patients were assessable (127 RT + CT patients and 116 RT patients). Progression-free and overall survival are significantly improved in the patients receiving CT. The hazard ratios for progression-free survival and overall survival in the RT only arm versus the RT + CT arm are 2.01 (P =.003) and 1.96 (P =. 007), respectively. The projected progression-free survivals at 4 years is 63% with RT and 80% with RT + CT. The projected overall survival rate at 4 years is 71% with RT and 81% with RT + CT. Grades 3 and 4 hematologic and gastrointestinal toxicity were more frequent in the RT + CT group.\n The addition of concurrent cisplatin-based CT to RT significantly improves progression-free and overall survival for high-risk, early-stage patients who undergo radical hysterectomy and pelvic lymphadenectomy for carcinoma of the cervix."
] |
We recommend surgery for early-stage AC of the uterine cervix in carefully staged patients. Primary chemoradiation remains a second best alternative for patients unfit for surgery; chemoradiation is probably first choice in patients with (MRI or PET-CT-suspected) positive lymph nodes. Since the last version of this review no new studies were found.
|
CD009187
|
[
"16954124",
"17204318",
"21667366",
"16377603",
"17995993",
"19017582",
"16788278",
"2189772",
"18407003",
"16873594",
"11802453",
"15586837",
"15586136",
"11900495"
] |
[
"Interest in an online smoking cessation program and effective recruitment strategies: results from Project Quit.",
"Recruiting pregnant smokers into a clinical trial: using a network-model managed care organization versus community-based practices.",
"A novel recruitment message to increase enrollment into a smoking cessation treatment program: preliminary results from a randomized trial.",
"A randomized controlled trial of multiple tailored messages for smoking cessation among callers to the cancer information service.",
"Proactive interventions for smoking cessation in general medical practice: a quasi-randomized controlled trial to examine the efficacy of computer-tailored letters and physician-delivered brief advice.",
"Comparing two web-based smoking cessation programs: randomized controlled trial.",
"Effectiveness of a low-intensity intra-worksite intervention on smoking cessation in Japanese employees: a three-year intervention trial.",
"Recruitment in a primary care trial on smoking cessation.",
"Web-based smoking-cessation programs: results of a randomized trial.",
"Integrated tobacco cessation counseling in a diabetes self-management training program: a randomized trial of diabetes and reduction of tobacco.",
"[The effect of smoking cessation counseling at health checkup].",
"Results of a randomized controlled trial of intervention to implement smoking guidelines in Veterans Affairs medical centers: increased use of medications without cessation benefit.",
"Motivational interviewing as a smoking cessation intervention for patients with cancer: randomized controlled trial.",
"Efficacy of resident training in smoking cessation: a randomized, controlled trial of a program based on application of behavioral theory and practice with standardized patients."
] |
[
"The Internet is a promising venue for delivering smoking cessation treatment, either as a stand-alone program or as an adjunct to pharmacotherapy. However, there is little data to indicate what percent of smokers are interested in receiving online smoking cessation services or how best to recruit smokers to Internet-based programs.\n Using a defined recruitment sample, this study aimed to identify the percentage of smokers who expressed interest in or enrolled in Project Quit, a tailored, online, cognitive-behavioral support program offered with adjunctive nicotine replacement therapy patches. In addition, we examined the effectiveness of several individual-level versus population-level recruitment strategies.\n Members from two large health care organizations in the United States were invited to participate in Project Quit. Recruitment efforts included proactive invitation letters mailed to 34533 likely smokers and reactive population-level study advertisements targeted to all health plan members (> 560000 adults, including an estimated 98000 smokers across both health care organizations).\n An estimated 1.6% and 2.5% of adult smokers from each health care organization enrolled in Project Quit. Among likely smokers who received proactive study invitations, 7% visited the Project Quit website (n = 2260) and 4% (n = 1273) were eligible and enrolled. Response rates were similar across sites, despite using different sources to assemble the invitation mailing list. Proactive individual-level recruitment was more effective than other forms of recruitment, accounting for 69% of website visitors and 68% of enrollees.\n Smokers were interested in receiving online smoking cessation support, even though they had access to other forms of treatment through their health insurance. Uptake rates for this program were comparable to those seen when smokers are advised to quit and are referred to other forms of smoking cessation treatment. In this sample, proactive mailings were the best method for recruiting smokers to Project Quit.",
"Recruiting pregnant smokers into smoking cessation intervention trials is challenging. Changes in health care systems offer new opportunities to overcome many of the obstacles encountered by researchers attempting to address the significant harm from maternal smoking. Investigators could facilitate smoking cessation study recruitment by collaborating with health care systems that systematically collect patient smoking status and record it in a centralized, retrievable fashion. This paper reports the results of utilizing this novel approach and compares it with a typical decentralized practice-based recruitment strategy.\n The study was conducted at Massachusetts General Hospital, in Boston, Massachusetts, from 2000 to 2005. Four hundred forty-two pregnant smokers were recruited for a randomized controlled trial of telephone-delivered smoking counseling from two sources: a network-model managed care health plan and community-based practices (CBP). At the health plan, study recruitment was built on an existing system that permitted pregnant smokers to be identified centrally. At the CBPs, identification and referral systems had to be developed at each practice specifically for the study. The two strategies were compared on the efficiency of recruitment, characteristics of enrollees, and study outcome and process measures.\n The health plan strategy generated referrals nearly twice as fast as the CBP strategy (30.4 vs. 17.0 per month), but because referrals were not timely, a large proportion of women from the plan were too advanced in pregnancy to be eligible to enroll in the study. As a result, the two strategies yielded a comparable enrollment rate. Participants from the health plan were older, better educated, less racially diverse, more likely to be living with the baby's father, and less likely to have smokers in their environment. These differences were largely explained by the socioeconomic diversity of women recruited from the CBPs. Smoking cessation outcomes did not differ by recruitment source.\n A recruitment strategy using a health plan's centralized system was more efficient than a practice-based recruitment strategy at identifying potential study participants, but less efficient at generating study participants from the referrals received. Importantly, participants recruited by the two strategies differed by socioeconomic, but not cessation-related, characteristics. To date, recruiting pregnant smokers into intervention studies remains resource intensive and time consuming. Participant identification and recruitment will be greatly enhanced by health system innovations such as implementation of electronic medical records.",
"Most smokers do not utilize approved interventions for nicotine dependence, reducing the probability of cessation. Smoking cessation programs typically use recruitment messages emphasizing the health threats of smoking. Augmenting this threat message by describing the genetic aspects of nicotine addiction may enhance enrollment into a cessation program. During telephone recruitment, 125 treatment-seeking smokers were randomized to receive by phone either a standard threat message or a threat plus genetic prime message and were offered open-label varenicline and counseling. There was a greater rate of enrollment into the cessation program for the threat plus genetic prime participants (51.7%) versus the threat-only participants (37.7%; p = .03). Smokers who self-identified from racial/ethnic minority groups were less likely to enroll in the cessation program (p = .01) versus smokers who self-identified as Caucasian. These preliminary data suggest that a simple, affordable, and transportable communication approach enhances enrollment of smokers into a smoking cessation program. A larger clinical trial to evaluate a genetic prime message for improving recruitment into smoking cessation programs is warranted.",
"Self-help materials computer-tailored to the specific needs of smokers have shown promise as a high-reach, low-cost intervention for smoking cessation. Adding tailored cessation materials to telephone-based cessation counseling may be a way of generating greater efficacy in promoting and maintaining cessation. The objective of this study is to assess the efficacy of adding different types of behavioral smoking cessation materials to brief telephone-based cessation counseling.A total of 1,978 smokers calling the National Cancer Institute's (NCI's) Cancer Information Service (CIS) for help in quitting smoking initially received brief cognitive-behavioral cessation counseling from a CIS information specialist. Following a baseline interview administered by the information specialist, subjects were randomly assigned to one of four conditions, each delivered by U.S. mail: a single, untailored smoking cessation guide (SU); a single, tailored smoking cessation guide (ST); a series of four (multiple) printed materials tailored only to baseline data (MT); and a series of four (multiple) printed materials tailored to baseline as well as retailored using 5-month interim progress data (MRT). The primary outcome measure was 7-day point prevalence abstinence rates assessed using a computer-assisted telephone interview (CATI) at 12-month follow-up.At 12-month follow-up, using intent-to-treat, imputed, and per-protocol analyses, no differences were found among the four experimental conditions (linear trend), or when the ST, MT, and MRT groups were compared with the control (SU) group. Participants in the two multiple message group conditions combined (MT + MRT), however, had significantly higher abstinence rates than participants in the two single message group conditions combined (SU + ST). Moreover, among subjects who reported quitting at the 5-month follow-up, participants receiving the MRT materials reported higher abstinence rates at 12 months than the other three groups combined (SU + ST + MT). The results of this study support the effectiveness, over and above a single telecounseling interaction, of multiple tailored print material contacts on cessation. These effects, however may be due to tailoring, or the longitudinal nature of the two multiple tailored conditions, or both. The strongest evidence for tailoring occurred in the MRT condition for relapse prevention, suggesting that print materials tailored to interim progress may be especially effective in this context. The qualities of specific psychosocial and communication elements in tailored materials should receive attention in future research.",
"To test the efficacy of (i) computer-generated tailored letters and (ii) practitioner-delivered brief advice for smoking cessation against an assessment-only condition; and to compare both interventions directly.\n Quasi-randomized controlled trial.\n A total of 34 randomly selected general practices from a German region (participation rate 87%).\n A total of 1499 consecutive patients aged 18-70 years with daily cigarette smoking (participation rate 80%).\n The tailored letters intervention group received up to three individualized personal letters. Brief advice was delivered during routine consultation by the practitioner after an onsite training session. Both interventions were based on the Transtheoretical Model of behaviour change.\n Self-reported point prevalence and prolonged abstinence at 6-, 12-, 18- and 24-month follow-ups.\n Among participants completing the last follow-up, 6-month prolonged abstinence was 18.3% in the tailored letters intervention group, 14.8% in the brief advice intervention group and 10.5% in the assessment-only control group. Assuming those lost to follow-up to be smokers, the rates were 10.2%, 9.7% and 6.7%, respectively. Analyses including all follow-ups confirmed statistically significant effects of both interventions compared to assessment only. Using complete case analysis, the tailored letters intervention was significantly more effective than brief advice for 24-hour [odds ratio (OR) = 1.4; P = 0.047] but not for 7-day point prevalence abstinence (OR = 1.4; P = 0.068) for prolonged abstinence, or for alternative assumptions about participants lost to follow-up.\n The study demonstrated long-term efficacy of low-cost interventions for smoking cessation in general practice. The interventions are suitable to reach entire populations of general practices and smoking patients. Computer-generated letters are a promising option to overcome barriers to provide smoking cessation counselling routinely.",
"Smoking cessation remains a significant public health problem. Innovative interventions that use the Internet have begun to emerge that offer great promise in reaching large numbers of participants and encouraging widespread behavior change. To date, the relatively few controlled trials of Web-based smoking cessation programs have been limited by short follow-up intervals.\n We describe the 6-month follow-up results of a randomized controlled trial in which participants recruited online were randomly assigned to either a Web-based smoking cessation program (Quit Smoking Network; QSN) or a Web-based exercise enhancement program (Active Lives) adapted somewhat to encourage smoking cessation.\n The study was a two-arm randomized controlled trial that compared two Web-based smoking cessation programs: (1) the QSN intervention condition presented cognitive-behavioral strategies, and (2) the Active Lives control condition provided participants with guidance in developing a physical activity program to assist them with quitting. The QSN condition provided smoking cessation information and behavior change strategies while the Active Lives condition provided participants with physical activity recommendations and goal setting. The QSN condition was designed to be more engaging (eg, it included multimedia components) and to present much greater content than is typically found in smoking cessation programs.\n Contrary to our hypotheses, no between-condition differences in smoking abstinence were found at 3- and 6-month follow-up assessments. While participants in the QSN intervention condition spent more time than controls visiting the online program, the median number of 1.0 visit in each condition and the substantial attrition (60.8% at the 6-month follow-up) indicate that participants were not as engaged as we had expected.\n Contrary to our hypothesis, our test of two Web-based smoking cessation conditions, an intervention and an attention placebo control, failed to show differences at 3- and 6-month assessments. We explored possible reasons for this finding, including limited engagement of participants and simplifying program content and architecture. Future research needs to address methods to improve participant engagement in online smoking cessation programs. Possible approaches in this regard can include new informed consent procedures that better explain the roles and responsibilities of being a research participant, new program designs that add more vitality (changing content from visit to visit), and new types of reminders pushed out to participants to encourage return visits. Simplifying program content through a combination of enhanced tailoring and information architecture also merits further research attention.",
"To test the effectiveness of a low-intensity intervention program for smoking cessation targeting the worksite environment in employees who had a low readiness to quit, we conducted an intervention trial at six intervention and six control worksites in Japan. A total of 2,307 smokers at baseline who remained at their worksite throughout the three-year study period were analyzed (1,017 in intervention and 1,290 in control groups). The multi-component program at the worksites consisted of (1) presenting information on the harms of tobacco smoking and the benefits of cessation by posters, websites, and newsletters; (2) smoking cessation campaigns for smokers; (3) advice on designation of smoking areas; and (4) periodic site-visits of the designated smoking areas by an expert researcher. At baseline, the intervention and control groups each had high prevalence of immotive or precontemplation, that reflected low readiness to quit (71.5% and 73.2%, respectively). The smoking cessation rate, as not having smoked for the preceding six months or longer, assessed at 36 months after the baseline survey by a self-administered questionnaire was significantly higher in the intervention group than the control group (12.1%, vs. 9.4%, p=0.021). The intervention program still had a significant effect on the smoking cessation rate after multiple logistic regression analysis adjusted for sex, age, type of occupation, age of starting smoking, quit attempts in the past, number of cigarettes per day, and readiness to quit (odds ratio: 1.38, 95% confidence interval: 1.05-1.81, p=0.02). The cost per additional quitter due to the intervention was calculated to be Yen 70,080. These findings indicate that this program is effective and can be implemented in similar workplaces where the prevalence of smoking is high and smokers' readiness to cease smoking is low.",
"The purpose of this study was to describe and compare the rates of recruitment during a randomized clinical trial on smoking cessation in two primary care practices. One site was a five-physician private family practice setting with about 15,000 patients. During 34 days, 576 patients were screened, of whom 22% were smokers. Among the smokers screened, 54% consented, 33% refused consent, and 13% were called in too early to consent. The other site was a six-physician academic medical practice with about 16,000 patients. During 53 days, 1,692 subjects were screened, of whom 16.2% were smokers. Among the smokers, 19% consented, 81% refused consent, and none were called in early. The enrollment of smokers was 3.3 times greater in the private practice than the academic practice. At the first site, study personnel screened 26.6 subjects per day, whereas the practice receptionist screened only 13.4 subjects per day (P less than .01). A randomized trial of having subjects read the informed consent versus having study personnel read it to them showed no differences in recruitment. The data suggest that private practices may have greater potential for subject recruitment than academic sites, that using study personnel improves recruitment, and that having study personnel actively involved in informed consent does not improve recruitment.",
"Initial trials of web-based smoking-cessation programs have generally been promising. The active components of these programs, however, are not well understood. This study aimed to (1) identify active psychosocial and communication components of a web-based smoking-cessation intervention and (2) examine the impact of increasing the tailoring depth on smoking cessation.\n Randomized fractional factorial design.\n Two HMOs: Group Health in Washington State and Henry Ford Health System in Michigan.\n 1866 smokers.\n A web-based smoking-cessation program plus nicotine patch. Five components of the intervention were randomized using a fractional factorial design: high- versus low-depth tailored success story, outcome expectation, and efficacy expectation messages; high- versus low-personalized source; and multiple versus single exposure to the intervention components.\n Primary outcome was 7 day point-prevalence abstinence at the 6-month follow-up.\n Abstinence was most influenced by high-depth tailored success stories and a high-personalized message source. The cumulative assignment of the three tailoring depth factors also resulted in increasing the rates of 6-month cessation, demonstrating an effect of tailoring depth.\n The study identified relevant components of smoking-cessation interventions that should be generalizable to other cessation interventions. The study also demonstrated the importance of higher-depth tailoring in smoking-cessation programs. Finally, the use of a novel fractional factorial design allowed efficient examination of the study aims. The rapidly changing interfaces, software, and capabilities of eHealth are likely to require such dynamic experimental approaches to intervention discovery.",
"The purpose of this study was to evaluate the impact of a tobacco cessation intervention using motivational interviewing on smoking cessation rates during diabetes self-management training (DSMT).\n A randomized controlled trial was conducted with subjects recruited from an ongoing type 2 diabetes adult education program at a large diabetes center. A total of 114 subjects were randomized to intervention (n = 57; face-to-face motivational interviewing plus telephone counseling and offering of medication) or standard care (n = 57). Outcome measures included tobacco cessation rates, mean number of cigarettes smoked, A1C, weight, blood pressure, and lipids.\n Intensive intervention using motivational interviewing integrated into a standard DSMT program resulted in a trend toward greater abstinence at 3 months of follow-up in those receiving the intervention. However, this same trend was not observed at 6 months. The addition of this structured smoking cessation intervention did not negatively affect either diabetes education or other measures of diabetes management, including A1C values.\n Structured tobacco cessation efforts can be readily integrated into established diabetes education programs without a negative impact on diabetes care or delivery of diabetes education. However, an intervention of moderate intensity for smoking cessation was no more effective than usual care in assisting patients with tobacco cessation after 6-month follow-up. Whether a more intensive intervention, targeting patients expressing a readiness to discontinue tobacco use, and/or a longer duration or a more cumulative effect of treatment will be more effective must be evaluated.",
"Smoking cessation counseling is an important element of tobacco control in the workplace, but it is not easy to persuade workers to stop smoking. We performed a controlled intervention trial to evaluate the effectiveness of a new cessation program developed by Nakamura et al., which consisted of one brief individual counseling session and 4 follow-up telephone calls. Two hundred and twenty-eight smokers who visited our center for an annual health checkup were randomly divided into two group: 117 were assigned to the intervention group, and 111 were controls. Smoking status questionnaires were administered to assess the smoking habit of each subject and to evaluate their stages of change toward smoking cessation before the counseling session. Stage-matched cessation counseling was then provided to the intervention group by nurses who had completed training courses for this program. During the counseling session, carbon monoxide in expired air and nicotine metabolites in urine were measured to enhance self-perception of smoking. Only those clients who set a quit date during their counseling sessions received follow-up telephone calls. It was easy to implement this program (15 to 20 minutes long) during a health checkup. No significant differences were observed in the baseline characteristics of the two groups. The cross-sectional smoking cessation rates at 6 months and 1 year of follow-up were 6.2 times higher in the intervention group than in the control group. The continuous smoking cessation rate at 1 year of follow-up was 7.6 times higher in the intervention group than in the control group. In the intervention group, the lower level of nicotine metabolites in urine and higher smoking stage were related to cessation success, but other baseline characteristics were similar in those who quit smoking and those who did not. The effectiveness and easy applicability of this cessation program was proved in the present study. Further examinations in various settings are expected to clarify the effectiveness of this program.",
"The AHRQ Clinical Practice Guideline for Treating Tobacco Use and Dependence recommends screening and treatment of all tobacco users. Effective methods to implement recommendations are needed because simple guideline dissemination does not necessarily result in changes in practice.\n The Guideline Implementation for Tobacco (GIFT) study tested an organizational intervention to improve Guideline implementation.\n GIFT randomized 20 Veterans Affairs medical centers to intervention or control conditions. We trained prime movers at each site to improve identification of smoking status, promote primary care interventions and increase availability of smoking cessation medications. Sites and patients were evaluated before and after intervention.\n GIFT included 20 Veterans Affairs medical centers and 5678 subjects.\n Data regarding smoking status, delivery of treatment, medication use, and smoking cessation were collected from participant surveys, medical record review, survey of site leaders, and Pharmacy Benefits Management.\n The intervention did not increase participant report of being asked about smoking status or receipt of counseling. It did increase the rate of identification of smoking status in the medical record (P = 0.0001) but did not increase the rate of counseling to stop smoking. Site level data showed no increase in the number of patients receiving smoking cessation medications or dollars spent on medications. Individual smoker data showed a significant increase in the use of medications for smoking cessation in intervention sites (odds ratio = 6.89, P < 0.0001); however, only a small minority of smokers received medication even after the intervention. There was no difference in smoking cessation rates between participants at the intervention and treatment sites.\n We conclude that improvements in smoking cessation rates are likely to require more intensive intervention in this population.",
"Smoking cessation of patients with cancer can improve treatment efficacy and survival.\n To determine whether a motivational interviewing intervention increased successful smoking cessation attempts of patients with cancer attending a South Australian public hospital, as compared with usual care.\n A randomized controlled trial was used to study 137 patients with mixed cancer sites, including 74 intervention patients and 63 control patients. The motivational interviewing intervention was delivered over a 3-month period. The intervention included a visit with a smoking cessation counselor, provision of smoking cessation booklets, nicotine replacement therapy, family advice to quit, and an in-person or telephone follow-up conversation.\n At the 6-month follow-up visit, an intention-to-treat analysis found no difference in biochemically confirmed 3-month prevalence quit rates between the intervention (5%) and control (6%) groups. A sensitivity analysis using more lenient criteria indicated quit rates of 29% for the intervention group and 18% for the control group (p = .32). The predictors of smoking cessation at 6 months for all the patients included a smoking-related cancer site, more cessation attempts in the year before enrollment in the study, and no radiation therapy.\n Future efforts to improve smoking cessation in this patient group might focus on the delivery of more direct methods for encouraging spouse cessation and support to the patient in quitting, and the use of bupropion (Zyban) as an adjunct to cessation for this heavy smoking patient group.",
"New educational programs must be developed to improve physicians' skills and effectiveness in counseling patients about smoking cessation.\n To assess the efficacy of an educational program based on behavioral theory, active learning methods, and practice with standardized patients in helping patients abstain from smoking and changing physicians' counseling practices.\n Cluster randomized, controlled trial.\n Two general internal medicine clinics in Switzerland.\n 35 residents and 251 consecutive smoking patients.\n A training program administered over two half-days, during which physicians learned to provide counseling that matched smokers' motivation to quit and practiced these skills with standardized patients acting as smokers at different stages of change. The control intervention was a didactic session on management of dyslipidemia.\n Self-reported abstinence from smoking at 1 year of follow-up, which was validated by exhaled carbon monoxide testing at one clinic; score of overall quality of counseling based on use of 14 counseling strategies; patient willingness to quit; and daily cigarette consumption.\n At 1 year of follow-up, abstinence from smoking was significantly higher in the intervention group than in the control group (13% vs. 5%; P = 0.005); this corresponded to a cluster-adjusted odds ratio of 2.8 (95% CI, 1.4 to 5.5). Residents who received the study training provided better counseling than did those who received the control training (mean score, 4.0 vs. 2.7; P = 0.002). Smokers' willingness to quit was also higher in the intervention group (94% vs. 80%; P = 0.007). A nonsignificant trend toward lower daily cigarette consumption in the intervention group was observed.\n A training program in smoking cessation administered to physicians that was based on behavioral theory and practice with standardized patients significantly increased the quality of physicians' counseling, smokers' motivation to quit, and rates of abstinence from smoking at 1 year."
] |
The substantial heterogeneity across the included studies restricts our ability to draw firm conclusions about the effectiveness of different recruitment strategies in relation to recruitment of participants into smoking cessation programmes or levels of smoking cessation. The limited evidence, however, suggests that the following elements may improve the recruitment of smokers into cessation programmes: personal, tailored interventions; recruitment methods that are proactive in nature; and more intensive recruitment strategies (i.e., those strategies that require increased contact with potential participants).
|
CD001945
|
[
"9690695",
"11206599",
"16199834"
] |
[
"An exploratory haloperidol-controlled dose-finding study of ziprasidone in hospitalized patients with schizophrenia or schizoaffective disorder.",
"Intramuscular ziprasidone compared with intramuscular haloperidol in the treatment of acute psychosis. Ziprasidone I.M. Study Group.",
"Olanzapine versus ziprasidone: results of a 28-week double-blind study in patients with schizophrenia."
] |
[
"Ninety patients with schizophrenia or schizoaffective disorder according to DSM-III-R criteria participated in this double-blind, exploratory, dose-ranging trial. After a single-blind washout period of 4 to 7 days, patients were randomly assigned to receive one of four fixed doses of the new antipsychotic, ziprasidone 4 (N = 19), 10 (N = 17), 40 (N = 17), or 160 (N = 20) mg/day or haloperidol 15 mg/day (N = 17) for 4 weeks. A dose-response relationship among ziprasidone groups was established for improvements in Clinical Global Impression Severity (CGI-S) score (p = 0.002) but not in Brief Psychiatric Rating Scale (BPRS) total score (p = 0.08). The intent-to-treat analysis of mean changes from baseline in the BPRS total, BPRS Psychosis core, and CGI-S scores demonstrated that ziprasidone 160 mg/day was comparable with haloperidol in reducing overall psychopathology and positive symptoms and was superior to ziprasidone 4 mg/day. Despite the small sample size and short duration of the trial, the improvement in CGI-S with both ziprasidone 160 mg/day and haloperidol 15 mg/day was statistically significantly greater than with ziprasidone 4 mg/day (p = 0.001 andp = 0.005, respectively). The percentage of patients classified as responders on both the BPRS total (> or = 30% improvement) and CGI-Improvement (score of 1 or 2) scales in the ziprasidone 160 mg/day group was similar to that in the haloperidol group and nonsignificantly greater than that in the ziprasidone 4 mg/day group. On all assessments of clinical efficacy, the improvements associated with ziprasidone 4 mg/day, 10 mg/day, and 40 mg/day were similar. Concomitant benztropine use at any time during the study was less frequent with ziprasidone 160 mg/day (15%) than with haloperidol (53%). Haloperidol was associated with a sustained hyperprolactinemia, unlike ziprasidone, where only transient elevations in prolactin that returned to normal within the dosing interval were observed. Ziprasidone was well tolerated, and the incidence of adverse events was similar in all groups. The results of this study suggest that ziprasidone 160 mg/day is as effective as haloperidol 15 mg/day in reducing overall psychopathology and positive symptoms of an acute exacerbation of schizophrenia or schizoaffective disorder but has a lower potential to induce extrapyramidal symptoms.",
"This 7-day, randomized, open-label, multicenter, international study compared the efficacy and tolerability of intramuscular (i.m.) ziprasidone with haloperidol i.m. and the transition from i.m. to oral treatment in hospitalized patients with acute psychotic agitation (related to DSM-III-R diagnoses).\n Patients received up to 3 days of flexible-dose ziprasidone i.m. (N = 90) or haloperidol i.m. (N = 42) followed by oral treatment to day 7. After an initial ziprasidone i.m. dose of 10 mg, subsequent i.m. doses of 5 to 20 mg could be given every 4 to 6 hours (maximum daily dose = 80 mg) if needed, followed by oral ziprasidone, 80-200 mg/day. Haloperidol i.m. doses of 2.5 to 10 mg were given on entry, followed by 2.5 to 10 mg i.m. every 4 to 6 hours (maximum daily dose = 40 mg) if needed, then by oral haloperidol, 10-80 mg/day.\n The mean reductions in Brief Psychiatric Rating Scale (BPRS) total, BPRS agitation items, and Clinical Global Impressions-Severity scale scores were statistically significantly greater (p < .05, p < .01, and p < .01, respectively) after ziprasidone i.m. treatment compared with haloperidol i.m. treatment. Further reductions in these scores also occurred in both groups following transition to oral treatment. Ziprasidone was associated with a lower incidence of movement disorders and a reduced requirement for anticholinergic medication during both i.m. and oral treatment compared with haloperidol. Movement disorder scale scores improved with ziprasidone i.m. and oral treatment, but deteriorated with haloperidol. Other adverse events were rare with both treatments.\n Ziprasidone i.m. was significantly more effective in reducing the symptoms of acute psychosis and was better tolerated than haloperidol i.m., particularly in movement disorders. The transition from ziprasidone i.m. to oral ziprasidone was effective and well tolerated.",
"The efficacy and safety of olanzapine were compared with those of ziprasidone.\n This was a multicenter randomized, double-blind, parallel-group, 28-week study of patients with schizophrenia. Patients were randomly assigned to treatment with 10-20 mg/day of olanzapine or 80-160 mg/day of ziprasidone. The primary efficacy measure was the Positive and Negative Syndrome Scale total score. Secondary efficacy and safety measures included Positive and Negative Syndrome Scale subscales as well as mood, quality of life, and extrapyramidal symptom scales. Safety was evaluated by recording treatment-emergent adverse events and measuring vital signs and weight.\n The study was completed by significantly more olanzapine-treated patients (165 of 277, 59.6%) than ziprasidone-treated patients (115 of 271, 42.4%). At 28 weeks, the olanzapine-treated patients showed significantly more improvement than the ziprasidone-treated patients on the Positive and Negative Syndrome Scale overall scale and all subscales and on the Clinical Global Impression ratings of severity of illness and improvement. The responder rate was higher for olanzapine than for ziprasidone. Extrapyramidal symptoms were not significantly different between groups in change-to-endpoint analyses, but results favored olanzapine on baseline-to-maximum changes. Weight change was significantly greater with olanzapine (mean=3.06 kg, SD=6.87) than with ziprasidone (mean=-1.12 kg, SD=4.70). Fasting lipid profiles were significantly superior in the ziprasidone group; there was no significant difference in fasting glucose level.\n Olanzapine treatment resulted in significantly greater psychopathology improvement and higher response and completion rates than ziprasidone treatment, while ziprasidone was superior for weight change and lipid profile."
] |
Currently data are limited. Ziprasidone may be an effective antipsychotic with less extrapyramidal effects than haloperidol. It also, however, causes more nausea and vomiting than the typical drugs, and, at present, there is no data suggesting that it is different to other atypical compounds. Well planned, conducted and reported long term randomised trials are needed if ziprasidone is to be accepted into everyday use.
|
CD009584
|
[
"22170366",
"20332221",
"19225128",
"10103334"
] |
[
"A novel fortified blended flour, corn-soy blend \"plus-plus,\" is not inferior to lipid-based ready-to-use supplementary foods for the treatment of moderate acute malnutrition in Malawian children.",
"Effectiveness of ready-to-use therapeutic food compared to a corn/soy-blend-based pre-mix for the treatment of childhood moderate acute malnutrition in Niger.",
"Supplementary feeding with fortified spreads results in higher recovery rates than with a corn/soy blend in moderately wasted children.",
"Zinc supplementation in malnourished children with persistent diarrhea in Pakistan."
] |
[
"Children with moderate acute malnutrition (MAM) are often treated with fortified blended flours, most commonly a corn-soy blend (CSB). However, recovery rates remain <75%, lower than the rate achieved with peanut paste-based ready-to-use supplementary foods (RUSFs). To bridge this gap, a novel CSB recipe fortified with oil and dry skim milk, \"CSB++,\" has been developed.\n In this trial we compared CSB++ with 2 RUSF products for the treatment of MAM to test the hypothesis that the recovery rate achieved with CSB++ will not be >5% worse than that achieved with either RUSF.\n We conducted a prospective, randomized, investigator-blinded, controlled noninferiority trial involving rural Malawian children aged 6-59 mo with MAM. Children received 75 kcal CSB++ · kg(-1) · d(-1), locally produced soy RUSF, or an imported soy/whey RUSF for ≤12 wk.\n The recovery rate for CSB++ (n = 763 of 888; 85.9%) was similar to that for soy RUSF (795 of 806, 87.7%; risk difference: -1.82%; 95% CI: -4.95%, 1.30%) and soy/whey RUSF (807 of 918, 87.9%; risk difference: -1.99%; 95% CI: -5.10%, 1.13%). On average, children who received CSB++ required 2 d longer to recover, and the rate of weight gain was less than that with either RUSF, although height gain was the same among all 3 foods studied.\n A novel, locally produced, fortified blended flour (CSB++) was not inferior to a locally produced soy RUSF and an imported soy/whey RUSF in facilitating recovery from MAM. The recovery rate observed for CSB++ was higher than that for any other fortified blended flour tested previously. This trial is registered at clinicaltrials.gov as NCT00998517.",
"Standard nutritional treatment of moderate acute malnutrition (MAM) relies on fortified blended flours though their importance to treat this condition is a matter of discussion. With the newly introduced World Health Organization growth standards, more children at an early stage of malnutrition will be treated following the dietary protocols as for severe acute malnutrition, including ready-to-use therapeutic food (RUTF). We compared the effectiveness of RUTF and a corn/soy-blend (CSB)-based pre-mix for the treatment of MAM in the supplementary feeding programmes (SFPs) supported by Médecins Sans Frontières, located in the Zinder region (south of Niger). Children measuring 65 to <110 cm, newly admitted with MAM [weight-for-height (WHM%) between 70% and <80% of the NCHS median] were randomly allocated to receive either RUTF (Plumpy'Nut®, 1000 kcal day(-1)) or a CSB pre-mix (1231 kcal day(-1)). Other interventions were similar in both groups (e.g. weekly family ration and ration at discharge). Children were followed weekly up to recovery (WHM% ≥ 85% for 2 consecutive weeks). In total, 215 children were recruited in the RUTF group and 236 children in the CSB pre-mix group with an overall recovery rate of 79.1 and 64.4%, respectively (p < 0.001). There was no evidence for a difference between death, defaulter and non-responder rates. More transfers to the inpatient Therapeutic Feeding Centre (I-TFC) were observed in the CSB pre-mix group (19.1%) compared to the RUTF group (9.3%) (p = 0.003). The average weight gain up to discharge was 1.08 g kg(-1) day(-1) higher in the RUTF group [95% confidence interval: 0.46-1.70] and the length of stay was 2 weeks shorter in the RUTF group (p < 0.001). For the treatment of childhood MAM in Niger, RUTF resulted in a higher weight gain, a higher recovery rate, a shorter length of stay and a lower transfer rate to the I-TFC compared to a CSB pre-mix. This might have important implications on the efficacy and the quality of SFPs.",
"Moderate childhood wasting is defined as having a weight-for-height Z-score (WHZ) < -2, but > or = -3. These children are typically given fortified corn/soy blended flour (CSB), but this intervention has shown limited effectiveness. Fortified spreads (FS) can be used as supplementary foods instead; they are energy-dense, lipid-based pastes with added powdered micronutrients. In this randomized clinical effectiveness trial, the recovery rates were compared among children with moderate wasting who received either milk/peanut FS, soy/peanut FS, or CSB. Children received isoenergetic quantities of food, 314 kJ x kg(-1) x d(-1), for up to 8 wk with biweekly follow-up. The primary outcome was recovery, defined as having a WHZ > -2. Time-event analysis was used to compare the recovery rate. A total of 1362 children were enrolled in the study. Children receiving soy/peanut FS had a similar recovery rate to those receiving milk/peanut FS and children in either FS group were more likely to recover than those receiving CSB (80% in both FS groups vs. 72% in the CSB group; P < 0.01). The rate of weight gain in the first 2 wk was greater among children receiving milk/peanut FS (2.6 g x kg(-1) x d(-1), n = 465) or children receiving soy/peanut FS (2.4 g x kg(-1) x d(-1), n = 450) than among children receiving CSB (2.0 g x kg(-1) x d(-1), n = 447; P < 0.05). Rates of length gain did not differ among the 3 groups. A total of 8% of children in each feeding group developed edema, indicative of severe malnutrition, while receiving supplemental feeding. We conclude that FS are superior supplementary foods to CSB for moderately wasted Malawian children.",
"To evaluate the potential benefit of dietary supplementation of a rice-lentil (Khitchri) and yogurt diet with 3 mg/kg/d of elemental zinc (as zinc sulfate) in hospitalized malnourished children (age 6-36 months) with persistent diarrhea for 14 days.\n Randomized, double-blind placebo-controlled trial.\n Nutrition Research Ward at the National Institute of Child Health, Karachi, Pakistan, where children were admitted for 14 days of inpatient supervised rehabilitation.\n Primary outcome: overall weight gain by day 14. Secondary outcomes: overall energy intake, stool output, time to diarrheal recovery and weight gain (>/=3 days), plasma zinc, copper, prealbumin, and insulin-like growth factor-1.\n Of 87 children randomized for supplementation with either zinc or placebo, the two groups were comparable at admission in terms of severity and duration of diarrhea, as well as nutritional and anthropometric parameters. The overall weight gain, stool volume, stool frequency, as well as the time taken for diarrheal recovery or steady weight gain, were comparable for both supplemented children and controls. Supplemented children had a significant improvement in plasma zinc levels and serum alkaline phosphatase by day 14 of therapy in comparison with controls. Plasma copper levels were low in both groups at admission and although an increase was seen in control children, levels decreased further after zinc supplementation. There was no significant difference between the two groups for hemoglobin, serum albumin, prealbumin, and plasma insulin-like growth factor-1 increments during the course of therapy. Evaluation of primary and secondary outcome criteria among the subset of children with plasma zinc levels <60 microg/d at admission did not reveal any significant differences.\n Although there was satisfactory recovery in malnourished children with persistent diarrhea receiving the Khitchri-yogurt diet, there was no evidence of improved weight gain or acceleration of recovery from diarrhea with zinc supplementation. In contrast, the reduction in plasma copper levels in zinc-supplemented malnourished children suggests that caution should be exercised in supplementing severely malnourished children with zinc alone."
] |
In conclusion, there is moderate to high quality evidence that both lipid-based nutrient supplements and blended foods are effective in treating children with MAM. Although lipid-based nutrient supplements (LNS) led to a clinically significant benefit in the number of children recovered in comparison with blended foods, LNS did not reduce mortality, the risk of default or progression to SAM. It also induced more vomiting. Blended foods such as CSB++ may be equally effective and cheaper than LNS. Most of the research so far has focused on industrialised foods, and on short-term outcomes of MAM. There are no studies evaluating interventions to improve the quality of the home diet, an approach that should be evaluated in settings where food is available, and nutritional education and habits are the main determinants of malnutrition. There are no studies from Asia, where moderate acute malnutrition is most prevalent.
|
CD005283
|
[
"11841067",
"9527402",
"15558520",
"11532112",
"8880241",
"8821843",
"14575293",
"15886217",
"11805387"
] |
[
"Biocompatible membranes do not promote graft recovery following cadaveric renal transplantation.",
"A multicenter comparison of dialysis membranes in the treatment of acute renal failure requiring dialysis.",
"A randomized controlled trial comparing intermittent with continuous dialysis in patients with ARF.",
"A randomized clinical trial of continuous versus intermittent dialysis for acute renal failure.",
"A randomized cross-over comparison of the hemodynamic response to intermittent hemodialysis and continuous hemofiltration in ICU patients with acute renal failure.",
"Effect of the membrane biocompatibility on nutritional parameters in chronic hemodialysis patients.",
"Continuous renal replacement therapy (CRRT) or intermittent hemodialysis (IHD)--what is the procedure of choice in critically ill patients?",
"Comparison of continuous and intermittent renal replacement therapy for acute renal failure.",
"Hemodynamic response to fluid withdrawal in overhydrated patients treated with intermittent ultrafiltration and slow continuous ultrafiltration: role of blood volume monitoring."
] |
[
"Controversy surrounds the role of biocompatible membrane dialyzers in treatment of acute renal failure. Studies that have shown a benefit have involved critically ill patients where renal recovery and patient mortality are influenced by other comorbid disease. The aim of the present work is to clarify this issue in a more homogeneous population of patients with acute renal failure following cadaveric renal transplantation.\n All patients with delayed graft function between January 1996 and February 1998 were randomized to receive either a biocompatible (BCM, polysulfone) membrane or bioincompatible (BICM, cuprophane) membrane for dialysis until onset of graft function.\n Forty-one patients were randomized, 23 to receive BCM and 18 BICM. Five patients (2 BCM, 3 BICM; p = NS) with primary non-function of graft were excluded from analysis, leaving 36 cases of acute tubular necrosis (ATN). Patient and donor characteristics were similar in both groups. The BCM group had significantly longer periods of dialysis dependency compared to the BICM group (14 vs 10 days; p = 0.03). There was a tendency towards higher serum creatinine levels in the short term in the BCM group (318 vs 164 micromol/l at 1 month (p = 0.1), 190 vs 169 micromol/l at latest visit (p = 0.07)) and a greater number of acute rejection episodes in the BCM group (3.7 vs 1.7 episodes per 100 days of dialysis dependency, p = 0.1). With an intention-to-treat analysis of all 41 patients originally randomized, there was no significant difference in time to graft recovery between the 2 groups (p = 0.18).\n In the setting of ARF posttransplantation, we have found no evidence to support the use of biocompatible membranes for dialysis. Rather, our study provides argument against a large benefit for the use of BCM in the recovery of ARF, as suggested by earlier studies.",
"The mortality of patients with acute renal failure (ARF) remains high, and in several large studies approaches 60%. This mortality is particularly high in patients with ARF who require dialysis and has not changed substantially over several years, despite the introduction of major advances in monitoring and treatment. Increasing prevalence of comorbidities has been suggested as the major factor in this persistently high mortality. This study investigates the potential role of the dialysis membrane on patient outcome in a prospective multicenter study of 153 patients with ARF requiring dialysis. The membrane assignment was made in alternating order and was limited to membranes with low complement activation (Biocompatible [BCM]) and cellulosic, high complement activation (Bioincompatible [BICM]). Both types of membranes were low-flux membranes. Patients were dialyzed with the assigned membrane until recovery, discharge from hospital, or death. The severity of illness of each patient was assessed using the APACHE II score at the time of initiation of dialysis. A logistic regression analysis was used to adjust for the APACHE II score. The results of the study showed a statistically significant difference in survival (57% in patients on BCM, 46% in patients on BICM; P = 0.03) and in recovery of renal function (64% in patients on BICM and 43% in patients on BICM; P = 0.001). These differences were particularly marked in the patients who were nonoliguric (>400 ml/d of urine output) at initiation of the study. In the subset of patients who were nonoliguric at the start of dialysis, a larger fraction (70%) became oliguric after initiating dialysis on a BICM membrane, in contrast to 44% who were initiated on a BCM membrane (P = 0.03). It is concluded that the biocompatibility of the dialysis membrane plays a role in the outcome of patients with ARF, particularly those who are nonoliguric at the time of initiation of dialysis.",
"Despite the widespread use of continuous renal replacement therapy in critically ill patients with acute renal failure (ARF), there are few data supporting its benefits over conventional intermittent hemodialysis (IHD). We sought to analyze differences in survival between modalities in a study that compared continuous venovenous hemodialysis (CVVHD) with IHD.\n Eighty critically ill patients with ARF requiring dialysis were randomized after stratification by severity of illness to treatment with CVVHD or IHD.\n There were no differences in survival or renal recovery between groups. In patients who died, mean survival time was 10.7 +/- 11.2 days for the IHD group versus 14.3 +/- 16.1 days for the CVVHD group (P = not significant). There was greater net volume removal in the CVVHD group during 72 hours. Declines in urine output during 72 hours were similar between groups. Mean arterial pressure off and on dialysis therapy was analyzed retrospectively. There was a significant decrease in mean arterial pressure for patients on IHD therapy not seen in those on CVVHD therapy, but this did not lead to a survival advantage.\n Despite greater volume control, CVVHD did not lead to an improvement in survival, preservation of urine output, or renal recovery compared with IHD in patients with ARF.",
"Acute renal failure (ARF) requiring dialysis in critically ill patients is associated with an in-hospital mortality rate of 50 to 80%. The worldwide standard for renal replacement therapy is intermittent hemodialysis (IHD). Continuous hemodialysis and hemofiltration techniques have recently emerged as alternative modalities. These two therapies have not been directly compared.\n A multicenter, randomized, controlled trial was conducted comparing two dialysis modalities (IHD vs. continuous hemodiafiltration) for the treatment of ARF in the intensive care unit (ICU). One hundred sixty-six patients were randomized. Principal outcome measures were ICU and hospital mortality, length of stay, and recovery of renal function.\n Using intention-to-treat analysis, the overall ICU and in-hospital mortalities were 50.6 and 56.6%, respectively. Continuous therapy was associated with an increase in ICU (59.5 vs. 41.5%, P < 0.02) and in-hospital (65.5 vs. 47.6%, P < 0.02) mortality relative to intermittent dialysis. Median ICU length of stay from the time of nephrology consultation was 16.5 days, and complete recovery of renal function was observed in 34.9% of patients, with no significant group differences. Despite randomization, there were significant differences between the groups in several covariates independently associated with mortality, including gender, hepatic failure, APACHE II and III scores, and the number of failed organ systems, in each instance biased in favor of the intermittent dialysis group. Using logistic regression to adjust for the imbalances in group assignment, the odds of death associated with continuous therapy was 1.3 (95% CI, 0.6 to 2.7, P = NS). A detailed investigation of the randomization process failed to explain the marked differences in patient assignment.\n A randomized controlled trial of alternative dialysis modalities in ARF is feasible. Despite the potential advantages of continuous techniques, this study provides no evidence of a survival benefit of continuous hemodiafiltration compared with IHD. This study did not control for other major clinical decisions or other supportive management strategies that are widely variable (for example, nutrition support, hemodynamic support, timing of initiation, and dose of dialysis) and might materially influence outcomes in ARF. Standardization of several aspects of care or extremely large sample sizes will be required to answer optimally the questions originally posed by this investigation.",
"To compare the hemodynamic response of ICU patients with acute renal failure of a 24-h continuous arteriovenous hemofiltration (CAVH) and that of patients with a 4-h intermittent hemodialysis (HD).\n Cross-over randomized clinical trial. The two periods to be compared were a 24-h CAVH and the 24-h encompassing a 4-h HD. These two periods were separated by a 24-h wash-out period.\n Ten bed medicosurgical ICU of a tertiary care center in Paris, France.\n Inclusion criterion was the requirement of replacement therapy for acute renal failure in patients already submitted to mechanical ventilation.\n CAVH was performed with Ringers' lactate used for restitution and infused before the hemofilter. The ultrafiltrate output was maintained at around 15 ml/min. HD was performed with a bicarbonate-buffered dialysate.\n Mean arterial pressure (MAP), use of adrenergic drugs, and change in body weight during each period.\n Twenty-seven consecutive patients were included, 15 CAVH-HD and 12HD-CAVH. CAVH and HD allowed the same metabolic efficacy. No hemodynamic parameter (MAP, amount of adrenergic drugs, change in body weight) differed between the two methods.\n CAVH is equivalent to HD in terms of MAP and the use of vasopressive drugs and fluids. Establishing the superiority of CAVH would require carefully controlled studies assessing either outcome or changes in tissue oxygenation.",
"Malnutrition is highly prevalent in chronic hemodialysis patients and is an important determinant of their morbidity and mortality. Several recent studies have suggested that the inflammatory response associated with the biocompatibility of the dialysis membranes is a potential contributing factor. In a prospective study of 159 new hemodialysis patients from two centers randomized to either a low-flux biocompatible (BCM) membrane or a low-flux bioincompatible (BICM) membrane, we measured the long-term effects of biocompatibility on several nutritional parameters, including estimated dry weight, serum albumin, insulin-like growth factor-1 (IGF-1), and prealbumin over 18 months. Our results show that the BCM group had a mean (+/- SD) increase in their dry weight of 2.96 +/- 6.88 kg at month 12 and 4.36 +/- 8.57 kg at month 18 (P < 0.05 vs. baseline for both), whereas no change in mean weight was observed in BICM group. Following initiation of hemodialysis, a significant increase was observed in serum albumin levels in both groups of patients. However, the biocompatible group had an earlier and more marked increase in serum albumin levels compared to the BICM group. The average increase in serum albumin compared to baseline was consistently greater than 0.25 g/dl after seven months in the BCM group, but did not reach this level until 12 months after initiation of dialysis in the BICM group. The difference between the groups was statistically significant at months 7, 8, and 10 (P < 0.05, higher in the BCM group). Furthermore, the overall difference in serum albumin concentration between the two groups was larger in the center where the dose of dialysis was equivalent (P < 0.001). A consistently higher value was also observed in IGF-1 levels for BCM patients compared to BICM group (P = NS). In a further analysis, changes in IGF-1 levels, but not prealbumin, predicted the subsequent changes in serum albumin. We conclude that biocompatible hemodialysis membranes favorably impact on the nutritional status of chronic hemodialysis patients, independently of the flux characteristics of the membranes, and that IGF-1 may be an early marker of nutritional status.",
"Although at present there is no prospective randomized study which could show significantly better survival of patients on continuous procedures, the majority of intensivists advocate this technique of renal function replacement due to generally accepted opinion that it has less effect on circulation of already hemodynamically unstable patients. In our prospective randomized study with 104 patients, we also did not observe any difference in 28 days survival, in total survival, as well as in circulatory instability between two treatment modalities. Even in subgroup of 80 patients with sepsis and septic shock there were no difference in survival. Sepsis was the underlying disorder in 52 and septic shock in 28 patients out of 104 patients analyzed in this study. Our prospective randomized study did not show a statistically significant difference between the two methods of renal replacement therapy. Survival rates were not affected and neither was the occurrence of hemodynamic instability. We believe that both methods are complementary; IHD for faster elimination of electrolytes and waste products elimination, CRRT for regulation of higher calories requirements and for hemodynamically unstable patients. The expectations that one method is superior to the other in the term of better survival have not been corroborated by the current data available in the literature. The choice of the method should be individualized. ARF, which is an integral part of MOF, is a problem frequently encountered in critically ill patient treated in the ICU, but outcome of these patients depends closely on the control of basic event. Evaluation of each of the supportive procedures is therefore hindered by the fact that the underlying disease has the crucial effect on survival and the type of supportive procedure less so.",
"Mortality rates of critically ill patients with acute renal failure (ARF) requiring renal replacement therapy (RRT) are high. Intermittent and continuous RRT are available for these patients on the intensive care units (ICUs). It is unknown which technique is superior with respect to patient outcome.\n We randomized 125 patients to treatment with either continuous venovenous haemodiafiltration (CVVHDF) or intermittent haemodialysis (IHD) from a total of 191 patients with ARF in a tertiary-care university hospital ICU. The primary end-point was ICU and in-hospital mortality, while recovery of renal function and hospital length of stay were secondary end-points.\n During 30 months, no patient escaped randomization for medical reasons. Sixty-six patients were not randomized for non-medical reasons. Of the 125 randomized patients, 70 were treated with CVVHDF and 55 with IHD. The two groups were comparable at the start of RRT with respect to age (62+/-15 vs 62+/-15 years, CVVHDF vs IHD), gender (66 vs 73% male sex), number of failed organ systems (2.4+/-1.5 vs 2.5+/-1.6), Simplified Acute Physiology Scores (57+/-17 vs 58+/-23), septicaemia (43 vs 51%), shock (59 vs 58%) or previous surgery (53 vs 45%). Mortality rates in the hospital (47 vs 51%, CVVHDF vs IHD, P = 0.72) or in the ICU (34 vs 38%, P = 0.71) were independent of the technique of RRT applied. Hospital length of stay in the survivors was comparable in patients on CVVHDF [median (range) 20 (6-71) days, n = 36] and in those on IHD [30 (2-89) days, n = 27, P = 0.25]. The duration of RRT required was the same in both groups.\n The present investigation provides no evidence for a survival benefit of continuous vs intermittent RRT in ICU patients with ARF.",
"Fluid overload may occur in patients with congestive heart failure, especially when there is associated acute renal failure. When the pharmacological approach is not sufficient to maintain the patient's fluid balance, extracorporeal therapies must be instituted. However, since the ultrafiltration rate may be faster than fluid refilling from the interstitial space, remarkable changes in the circulating blood volume may occur. This may finally result in further worsening of peripheral perfusion due to a significant drop in cardiac output. In order to prevent a fall in the circulating blood volume, slow continuous ultrafiltration (SCUF) should be employed instead of acute intermittent ultrafiltration (UF). To further improve the tolerance to extracorporeal ultrafiltration, the session can be driven by the relative blood volume change monitored on-line with adequate sensors and devices. We utilized one of these systems (Crit-Line, Hemametrics, USA) to compare the relative changes in blood volume during UF and SCUF in 22 patients with fluid overload. Variations in blood pressure were significantly greater with UF than with SCUF even in the presence of similar levels of fluid removal. The variations in blood pressure were paralleled by variations in blood volume, which were greater with UF than with SCUF. In conclusion, extracorporeal ultrafiltration can be used to control the fluid balance in congestive heart failure, but it is advisable to prescribe low ultrafiltration rates over an extended period of time. The use of on-line blood volume monitors can be of further help in improving tolerance and the hemodynamic response.\n Copyright 2002 S. Karger AG, Basel"
] |
There is no demonstrable clinical advantage to the use of BCM versus BICM in patients with ARF who require intermittent hemodialysis.
|
CD003540
|
[
"12391951",
"10404919",
"15762903",
"12746365"
] |
[
"Primary care guidelines on consultation practices: the effectiveness of computerized versus paper-based versions. A cluster randomized controlled trial among newly qualified primary care physicians.",
"Chronic care clinics: a randomized controlled trial of a new model of primary care for frail older adults.",
"Can computer-generated evidence-based care suggestions enhance evidence-based management of asthma and chronic obstructive pulmonary disease? A randomized, controlled trial.",
"Effect of a practice-based strategy on test ordering performance of primary care physicians: a randomized trial."
] |
[
"To compare the effects of computerized and paper-based versions of guidelines on recently qualified physicians' consultation practices.\n Two arm cluster randomized controlled trial. Physicians were randomized to receive computerized or textbook-based versions of the same guidelines for a 4-week study period. Physicians' compliance with guideline recommendations about laboratory, radiological, physical and other examinations, procedures, nonpharmacologic and pharmacologic treatments, physiotherapy, and referrals were measured by case note review.\n There were 139 recently qualified physicians working in 96 primary healthcare centers in Finland who participated in the study. Data on 4,633 patient encounters were abstracted, of which 3,484 were suitable for further analysis. Physicians' compliance with guidelines was high (over 80% for use of laboratory, radiology, physical examinations, and referrals). There were no significant differences in physicians' consultation practices in any of the measured outcomes between the computerized and textbook group.\n Guidelines are a useful source of information for recently qualified physicians working in primary care. However, the method of presentation of the guidelines (electronic or paper) does not have an effect on guideline use or their impact on decisions. Other factors should be considered when choosing the method of presentation of guidelines, such as information-seeking time, ease of use during the consultation, ability to update, production costs, and the physician's own preferences.",
"To determine whether a new model of primary care, Chronic Care Clinics, can improve outcomes of common geriatric syndromes (urinary incontinence, falls, depressive symptoms, high risk medications, functional impairment) in frail older adults.\n Randomized controlled trial with 24 months of follow-up. Physician practices were randomized either to the Chronic Care Clinics intervention or to usual care.\n Nine primary care physician practices that comprise an ambulatory clinic in a large staff-model HMO in western Washington State.\n Those patients aged 65 and older in each practice with the highest risk for being hospitalized or experiencing functional decline.\n Intervention practices (5 physicians, 96 patients) held half-day Chronic Care Clinics every 3 to 4 months. These clinics included an extended visit with the physician and nurse dedicated to planning chronic disease management; a pharmacist visit that emphasized reduction of polypharmacy and high-risk medications; and a patient self-management/support group. Control practices (4 physicians, 73 patients) received usual care.\n Changes in self-reported urinary incontinence, frequency of falls, depressive symptoms, physical function, and satisfaction were analyzed using an intention-to-treat analysis adjusted for baseline differences, covariates, and practice-level variation. Prescriptions for high-risk medications and cost/utilization data obtained from administrative data were similarly analyzed.\n After 24 months, no significant improvements in frequency of incontinence, proportion with falls, depression scores, physical function scores, or prescriptions for high risk medications were demonstrated. Costs of medical care including frequency of hospitalization, hospital days, emergency and ambulatory visits, and total costs of care were not significantly different between intervention and control groups. A higher proportion of intervention patients rated the overall quality of their medical care as excellent compared with control patients (40.0% vs 25.3%, P = .10).\n Although intervention patients expressed high levels of satisfaction with Chronic Care Clinics, improved outcomes for selected geriatric syndromes were not demonstrated. These findings suggest the need for developing greater system-wide support for managing geriatric syndromes in primary care and illustrate the challenges of conducting practice improvement research in a rapidly changing delivery system.",
"Translation of evidence-based guidelines into clinical practice has been inconsistent. We performed a randomized, controlled trial of guideline-based care suggestions delivered to physicians when writing orders on computer workstations.\n Inner-city academic general internal medicine practice.\n Randomized, controlled trial of 246 physicians (25 percent faculty general internists, 75 percent internal medicine residents) and 20 outpatient pharmacists. We enrolled 706 of their primary care patients with asthma or chronic obstructive pulmonary disease. Care suggestions concerning drugs and monitoring were delivered to a random half of the physicians and pharmacists when writing orders or filling prescriptions using computer workstations. A 2 x 2 factorial randomization of practice sessions and pharmacists resulted in four groups of patients: physician intervention, pharmacist intervention, both interventions, and controls. DATA EXTRACTION/COLLECTION METHODS: Adherence to the guidelines and clinical activity was assessed using patients' electronic medical records. Health-related quality of life, medication adherence, and satisfaction with care were assessed using telephone questionnaires.\n During their year in the study, patients made an average of five scheduled primary care visits. There were no differences between groups in adherence to the care suggestions, generic or condition-specific quality of life, satisfaction with physicians or pharmacists, medication compliance, emergency department visits, or hospitalizations. Physicians receiving the intervention had significantly higher total health care costs. Physician attitudes toward guidelines were mixed.\n Care suggestions shown to physicians and pharmacists on computer workstations had no effect on the delivery or outcomes of care for patients with reactive airways disease.",
"Numbers of diagnostic tests ordered by primary care physicians are growing and many of these tests seem to be unnecessary according to established, evidence-based guidelines. An innovative strategy that focused on clinical problems and associated tests was developed.\n To determine the effects of a multifaceted strategy aimed at improving the performance of primary care physicians' test ordering.\n Multicenter, randomized controlled trial with a balanced, incomplete block design and randomization at group level. Thirteen groups of primary care physicians underwent the strategy for 3 clinical problems (arm A; cardiovascular topics, upper and lower abdominal complaints), while 13 other groups underwent the strategy for 3 other clinical problems (arm B; chronic obstructive pulmonary disease and asthma, general complaints, degenerative joint complaints). Each arm acted as a control for the other.\n Primary care physician groups in 5 regions in the Netherlands with diagnostic centers recruited from May to September 1998.\n Twenty-six primary care physician groups, including 174 primary care physicians.\n During the 6 months of intervention, physicians discussed 3 consecutive, personal feedback reports in 3 small group meetings, related them to 3 evidence-based clinical guidelines, and made plans for change.\n According to existing national, evidence-based guidelines, a decrease in the total numbers of tests ordered per clinical problem, and of some defined inappropriate tests, is considered a quality improvement.\n For clinical problems allocated to arm A, the mean total number of requested tests per 6 months per physician was reduced from baseline to follow-up by 12% among physicians in the arm A intervention, but was unchanged in the arm B control, with a mean reduction of 67 more tests per physician per 6 months in arm A than in arm B (P =.01). For clinical problems allocated to arm B, the mean total number of requested tests per 6 months per physician was reduced from baseline to follow-up by 8% among physicians in the arm B intervention, and by 3% in the arm A control, with a mean reduction of 28 more tests per physician per 6 months in arm B than in arm A (P =.22). Physicians in arm A had a significant reduction in mean total number of inappropriate tests ordered for problems allocated to arm A, whereas the reduction in inappropriate test ordered physicians in arm B for problems allocated to arm B was not statistically significant.\n In this study, a practice-based, multifaceted strategy using guidelines, feedback, and social interaction resulted in modest improvements in test ordering by primary care physicians."
] |
The findings of this review do not provide sufficient evidence to support or resist a policy of altering the lengths of primary care physicians' consultations. Further trials are needed that focus on health outcomes and cost effectiveness.
|
CD004865
|
[
"7869205",
"7636658"
] |
[
"Efficacy and cost analysis of treating very low birth weight infants with erythropoietin during their first two weeks of life: a randomized, placebo-controlled trial.",
"Follow-up of very low birth weight infants after erythropoietin treatment to prevent anemia of prematurity."
] |
[
"We hypothesized that using a higher dose of erythropoietin (Epo) and starting treatment on the first day of life would reduce the transfusion requirements of ventilator-dependent and non-ventilator-dependent very low birth weight (VLBW) infants. Moreover, we hypothesized that this treatment would be cost-effective.\n We randomly assigned 20 ill newborn VLBW infants to receive either Epo (200 units/kg per day) or placebo during their first 2 weeks of life. The caregivers were unaware of the treatment assignments, and erythrocyte transfusions were administered according to hematocrit and signs of anemia.\n On day 1, reticulocyte counts and hematocrits were similar in the two groups. During the subsequent 2 weeks, reticulocyte counts of the placebo recipients fell significantly below those of the Epo recipients, but hematocrits in the two groups did not differ. More transfusions were received by the placebo recipients (mean = 1.4 per patient) than by the Epo recipients (mean = 0.2 per patient; p < 0.01). No adverse effects of Epo were noted, and the costs in the placebo group exceeded those in the Epo group.\n We conclude that administration of Epo to VLBW infants during the first 2 weeks of life results in fewer transfusions and is cost-effective.",
"Treatment with recombinant human erythropoietin (rHuEPO) stimulates erythropoiesis and reduces the need for transfusions in hospitalized preterm infants. The aim of our study was to follow very low birth weight infants after the initial 6 weeks of rHuEPO treatment.\n We randomly assigned 97 very low birth weight infants with a gestational age of 31 weeks or less and birth weight of 1500 gm or less to receive rHuEPO, 300 units/kg per week (erythropoietin (EPO) 300, n = 33), rHuEPO, 750 units/kg per week (EPO 750; n = 28), or no treatment (control, n = 36). The rHuEPO was administered from the first week of life for 6 weeks. After EPO therapy was discontinued, 75 neonates were followed weekly until discharge and at 3, 6, and 12 months of age.\n Mean numbers (+/- SD) of packed erythrocyte transfusions per patient from the time rHuEPO therapy was discontinued until discharge were 0.38 +/- 0.64 (EPO 300), 0.23 +/- 0.52 (EPO 750), 0.9 +/- 1.1 (control) (p < 0.05 in both EPO groups vs control). Mean reticulocyte counts at the sixth week were 6% +/- 2.2% (EPO 300), 6.9% +/- 2.2% (EPO 750), and 3.1% +/- 2.6% (control) in the three groups (p < 0.01 in both EPO groups vs control), and at the eighth week were 4.7% +/- 2.8% (EPO 300), 5.4% +/- 2.7% (EPO 750), and 2.6% +/- 2.2% (control) (p < 0.01 in both EPO groups vs control). Serum ferritin levels were significantly higher at the sixth week, and the percentage of hemoglobin F was significantly lower at 6, 8, and 10 weeks in the control group versus EPO groups. At 3, 6, and 12 months of age, there were no differences in reticulocytes, ferritin, HbF, and growth among groups.\n Preterm infants who received rHuEPO had a normal pattern of erythropoiesis after the drug was discontinued. These data provide strong evidence that the anemia of prematurity is the result of a transient developmental abnormality in EPO production."
] |
The use of early EPO did not significantly reduce the 'Use of one or more RBC transfusions' or the 'Number of transfusions per infant" compared with late EPO administration. The finding of a statistically significant increased risk of ROP (any grade) and a similar trend for ROP stage > 3 with early EPO treatment is of great concern.
|
CD001697
|
[
"10690979"
] |
[
"Randomized pilot trial of postoperative aspirin in subarachnoid hemorrhage."
] |
[
"To assess the safety and feasibility of a clinical trial on the effectiveness of acetylsalicylic acid (ASA) in subarachnoid hemorrhage (SAH).\n Several studies have indicated that increased platelet activity might be involved in the pathogenesis of delayed cerebral ischemia (DCI) after SAH.\n Fifty patients who had early surgery (< or =4 days) for a ruptured aneurysm were enrolled in this randomized, double-blind, placebo-controlled trial. Trial medication, consisting of suppositories with 100 mg ASA versus placebo, was started immediately after surgical clipping of the aneurysm and continued for 21 days. End points were functional outcome and quality of life at 4 months, clinical deterioration after operation, development of DCI, hypodense lesion on postoperative CT, and hemorrhagic complications.\n One-third of all patients with aneurysmal SAH were eligible for the trial. Fifteen of 26 patients receiving placebo deteriorated clinically versus 10 of 24 patients receiving ASA; 4 patients in each group deteriorated from DCI. Postoperative hypodensities on CT were observed in 27 patients, distributed equally in both groups. Functional outcome and quality-of-life scores were slightly in favor of patients who had received ASA, but not to a significant degree (p = 0.22). Two patients in the ASA group had an asymptomatic hemorrhagic complication, and one patient in the placebo group had a fatal and another a symptomatic hemorrhagic complication.\n This pilot study shows that a clinical trial of acetylsalicylic acid (ASA) in subarachnoid hemorrhage (SAH) is feasible and probably safe. The effectiveness of ASA on functional outcome and delayed cerebral ischemia has to be studied in a larger trial."
] |
Based upon the limited randomised controlled evidence available, the timing of surgery was not a critical factor in determining outcome following a subarachnoid haemorrhage. Since the publication of the only randomised controlled study in 1989, techniques for the treatment of subarachnoid haemorrhage have progressed, questioning the validity of the conclusions in the modern era. Currently, most neurovascular surgeons elect to operate within 3 or 4 days of the bleed in good grade patients to minimise the chances of a devastating rebleed. However, the treatment of patients in poorer grades warrants further scrutiny in a randomised controlled trial.
|
CD004078
|
[
"1997835",
"3276900",
"7995145",
"1900687",
"6512582",
"15108041",
"16823593",
"17375049",
"9350242",
"20490797",
"15256239",
"7851558",
"9484732",
"17008704",
"12827681",
"11896097",
"6423263",
"9440756"
] |
[
"Effective surgical adjuvant therapy for high-risk rectal carcinoma.",
"Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP protocol R-01.",
"Adjuvant preoperative radiotherapy for locally advanced rectal carcinoma. Results of a prospective, randomized trial.",
"[Cooperative study of surgical adjuvant chemotherapy for colorectal cancer (third report): five-year results. Cooperative Study Group of Surgical Adjuvant Chemotherapy for Colorectal Cancer in Japan].",
"Randomized study of systemic chemotherapy following complete excision of nonosseous sarcomas.",
"Randomized controlled trial of the efficacy of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil and uracil/tegafur.",
"Randomized trial of the efficacy of adjuvant chemotherapy for colon cancer with combination therapy incorporating the oral pyrimidine 1-hexylcarbamoyl-5-fluorouracil.",
"An individual patient data meta-analysis of adjuvant therapy with uracil-tegafur (UFT) in patients with curatively resected rectal cancer.",
"[Prospective controlled study on the usefulness of Carmofur as a postoperative adjuvant chemotherapy for colorectal cancer].",
"Final results of randomized trials by the National Surgical Adjuvant Study of Colorectal Cancer (NSAS-CC).",
"Neo-adjuvant chemotherapy for operable gastric cancer: long term results of the Dutch randomised FAMTX trial.",
"A randomized trial of postoperative adjuvant chemotherapy in non-small cell lung cancer (the second cooperative study). The Study Group of Adjuvant Chemotherapy for Lung Cancer (Chubu, Japan).",
"Postoperative adjuvant chemotherapy after curative resection of hepatocellular carcinoma: a randomized controlled trial.",
"Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203.",
"Randomised clinical trial of adjuvant postoperative RT vs. sequential postoperative RT plus 5-FU and levamisole in patients with stage II-III resectable rectal cancer: a final report.",
"Combined-modality treatment for resectable metastatic colorectal carcinoma to the liver: surgical resection of hepatic metastases in combination with continuous infusion of chemotherapy--an intergroup study.",
"Final results of a randomized trial on the treatment of rectal cancer with preoperative radiotherapy alone or in combination with 5-fluorouracil, followed by radical surgery. Trial of the European Organization on Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group.",
"Prospectively randomized trial of postoperative adjuvant chemotherapy in patients with high-risk colon cancer."
] |
[
"Radiation therapy as an adjunct to surgery for rectal cancer has been shown to reduce local recurrence but has not improved survival. In a previous study, combined radiation and chemotherapy improved survival significantly as compared with surgery alone, but not as compared with adjuvant radiation, which many regard as standard therapy. We designed a combination regimen to optimize the contribution of chemotherapy, decrease recurrence, and improve survival as compared with adjuvant radiation alone.\n Two hundred four patients with rectal carcinoma that was either deeply invasive or metastatic to regional lymph nodes were randomly assigned to postoperative radiation alone (4500 to 5040 cGy) or to radiation plus fluorouracil, which was both preceded and followed by a cycle of systemic therapy with fluorouracil plus semustine (methyl-CCNU).\n After a median follow-up of more than seven years, the combined therapy had reduced the recurrence of rectal cancer by 34 percent (P = 0.0016; 95 percent confidence interval, 12 to 50 percent). Initial local recurrence was reduced by 46 percent (P = 0.036; 95 percent confidence interval, 2 to 70 percent), and distant metastasis by 37 percent (P = 0.011; 95 percent confidence interval, 9 to 57 percent). In addition, combined therapy reduced the rate of cancer-related deaths by 36 percent (P = 0.0071; 95 percent confidence interval, 14 to 53 percent) and the overall death rate by 29 percent (P = 0.025; 95 percent confidence interval, 7 to 45 percent). Its acute toxic effects included nausea, vomiting, diarrhea, leukopenia, and thrombocytopenia. These effects were seldom severe. Severe, delayed treatment-related reactions, usually small-bowel obstruction requiring surgery, occurred in 6.7 percent of all patients receiving radiation, and the frequencies of these complications were comparable in both treatment groups.\n The combination of postoperative local therapy with radiation plus fluorouracil and systemic therapy with a fluorouracil-based regimen significantly and substantively improves the results of therapy for rectal carcinoma with a poor prognosis, as compared with postoperative radiation alone.",
"Information is presented from 555 patients with Dukes B and C rectal cancers treated by curative resection who were entered into the National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol R-01 between November 1977 and October 1986. Their average time on study was 64.1 months. The patients were randomized to receive no further treatment (184 patients), postoperative adjuvant chemotherapy with 5-fluorouracil, semustine, and vincristine (MOF) (187 patients), or postoperative radiation therapy (184 patients). The chemotherapy group, when compared with the group treated by surgery alone, demonstrated an overall improvement in disease-free survival (P = .006) and in survival (P = .05). Employing the proportional hazards model, a global test was used to determine the presence of treatment interactions. Investigation of stratification variables employed in this study indicated that sex, and to a lesser extent age and Dukes stage, made individual contributions to the disease-free survival and the survival benefit from chemotherapy. When evaluated according to sex, the benefit for chemotherapy at 5 years, both in disease-free survival (29% vs. 47%; P less than .001; relative odds, 2.00) and in survival (37% vs. 60%; P = .001; relative odds, 1.93), was restricted to males. When males were tested for age trend with the use of a logistic regression analysis, chemotherapy was found to be more advantageous in younger patients. When the group receiving post-operative radiation (4,600-4,700 rad in 26-27 fractions; 5,100-5,300 rad maximum at the perineum) was compared to the group treated only by surgery, there was an overall reduction in local-regional recurrence from 25% to 16% (P = .06). No significant benefit in overall disease-free survival (P = .4) or survival (P = .7) from the use of radiation has been demonstrated. The global test for interaction to identify heterogeneity of response to radiation within subsets of patients was not significant. In conclusion, this investigation has demonstrated a benefit from adjuvant chemotherapy (MOF) for the management of rectal cancer. The observed advantage was restricted to males. Postoperative radiation therapy reduced the incidence of local-regional recurrence, but it failed to affect overall disease-free survival and survival.",
"A prospective, randomized clinical trial was conducted by the Northwest Rectal Cancer Group to study the effects of preoperative radiotherapy given one week before surgery in locally advanced (tethered or fixed) rectal carcinoma.\n A total of 284 patients were entered into the trial between 1982 and 1986; 141 were allocated to receive surgical treatment alone, and 143 were allocated to receive preoperative radiotherapy. A 10 x 10 x 10 cm volume in the posterior pelvis, centered on the tumor, was irradiated at a dose of 20 Gy, divided into four daily fractions of 5 Gy each.\n No differences were observed in any of the clinicopathologic variables in the two arms of the trial; there were no striking down-staging effects in the irradiated tumors. After a minimum follow-up period of 96 months, the overall and cancer-related mortality rates were similar in both arms of the study (P = 0.21 and P = 0.09, respectively). There was a highly significant reduction in local recurrences in the irradiated group (12.8 percent x-ray therapy vs. 36.5 percent surgery; P = 0.0001). The majority of local recurrences after preoperative radiotherapy occurred inside the radiotherapy field (10 cases; 7 percent), with only six cases (5 percent) outside the field. No significant difference was observed in the rates of distant metastasis between the two treatment groups (P = 0.73).\n Although there is no statistically significant survival benefit in the whole series, there is a survival benefit for the subset of patients considered by the surgeon to have undergone a curative operation. We recommend that this form of adjuvant therapy should be offered to all patients with locally advanced rectal cancer who are to undergo radical surgery.",
"A randomized controlled study was carried out by the envelope method with 491 institutions in participation across the country in order to find an optimal surgical adjuvant chemotherapy for curatively resected colorectal cancer. The schedules for drug administration were different in four districts: ACNU + Futraful (FT) group and FT alone group in the Hokkaido-Shikoku district; the same schedule groups plus untreated group in the Chubu-Kinki district; MMC+FT group, FT alone group in the Tohoku-Kanto district; and ADM+FT group and FT alone group in the Chugoku-Kyushu district. The numbers of patients admitted to this study were 2,450 cases with colon cancer and 2,456 cases met the evaluation criteria of this study. The 5-year survival rate on the whole did not differ from combination therapy to single drug therapy in either colon cancer or rectal cancer, but in Dukes C rectal cancer the five-year survival rate tended to be higher with the combination therapies. In n2 (+) or a2(s) rectal cancer in particular, combination therapies with MMC and FT and with ADM and FT achieved significantly higher five-year survival rate, and the rate of local recurrence was significantly lower with ADM+FT.",
"Between June 1975 and April 1981, 61 of the 177 eligible patients whose nonosseous sarcomas of extremity or trunk origin had been completely excised primarily or after local recurrences agreed to participate in a randomized study of adjuvant chemotherapy. Dermatofibrosarcoma, lymphomas, myeloma, Kaposi's sarcoma, and embryonal rhabdomyosarcoma were excluded as were patients with significant second primary cancers and those who received either preoperative or postoperative radiation therapy. After stratification by anatomic status of disease, site of origin, and histologic grade, a random one half of the 61 participants began alternating courses of vincristine/cyclophosphamide/dactinomycin, and vincristine/doxorubicin/dacarbazine at six-week intervals for one year. The control group was evaluated at six-week intervals without adjuvant chemotherapy, but these patients were offered this chemotherapy later if they had progressive disease excised. Although 30% of the 61 patients experienced local recurrence of disease within the first five years after randomization, and only 54% were continuously disease free for five or more years, 82% were surviving at five years (Kaplan-Meier calculations) with a median follow-up of 64.3 months. Partial suppression of distant metastasis by adjuvant chemotherapy was apparent in the overall study, in the extremity tumor category, and in the subgroup of patients who had received limb-sparing surgery; however, no survival advantage for chemotherapy-treated patients was demonstrated. The 30 adjuvant chemotherapy-treated patients received a total of three thoracotomies as compared with 17 salvage thoracotomies for the 31 control patients; however, salvage surgery for local recurrences has been similar in the two groups. Recent improvement in the survival of patients with soft-tissue sarcomas is not necessarily a result of adjuvant chemotherapy or radiation therapy.",
"We investigated the efficacy and safety of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil (carmofur, HCFU) and uracil/tegafur (UFT).\n Patients with stage II, III, or IV (Dukes' B, C) colorectal cancer were enrolled and randomly assigned to one of three groups: an immunochemotherapy group (mitomycin C [MMC] + 5-fluorouracil [5-FU] + HCFU + OK-432), a chemotherapy group (MMC + 5-FU + HCFU), and a control group (surgery alone) for those with colon cancer (study 1); and an immunochemotherapy group (MMC + 5-FU + UFT + OK-432), a chemotherapy group (MMC + 5-FU + UFT), and a control group (surgery alone) for those with rectal cancer (study 2).\n A total of 760 patients with colon cancer and 669 patients with rectal cancer were entered into this randomized clinical trial (RCT). The incidence of side-effects was in the order of: immunochemotherapy group > chemotherapy group > control group in both the cohort of patients with colon cancer and the cohort with rectal cancer. In particular, the frequency of leucopenia and skin disorders was significantly higher than control groups. There were no severe adverse events such as death related to the adjuvant therapy. In both the colon cancer and rectal cancer cohorts, no significant difference in the 5-year survival rate and disease-free survival rate was noted among the three groups.\n The results of an RCT demonstrated that the combination of MMC + 5-FU + HCFU + OK-432 for colon cancer and that of MMC + 5-FU + UFT + OK-432 for rectal cancer could not prolong the survival of patients with surgically resected colorectal cancer, but that both combinations were well tolerated as adjuvant therapy. We investigated the efficacy and safety of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil (carmofur, HCFU) and uracil/tegafur (UFT).",
"The purpose of the present trial was to clarify the efficacy of postoperative adjuvant chemotherapy including an oral fluoropyrimidine anticancer drug, the 1-hexylcarbamoyl-5-fluorouracil (HCFU), for the treatment of colon cancer.\n Patients with clinical stage Dukes' B and C colon cancer, who had been treated surgically, were assigned to a chemotherapy group treated with mitomycin C, 5-fluorouracil (5-FU), and HCFU and to a control group that received no postoperative adjuvant chemotherapy.\n Of the 1,001 patients registered for the study, 17 (1.7%) were ineligible. The incidence of toxicity was significantly higher in the chemotherapy group than in the control group. However, there were few severe side effects and no deaths related to the treatment. Overall survival showed no significant difference between the groups. The disease-free survival or the recurrence-free intervals was significantly higher in the chemotherapy group than in the control group. The incidence of hepatic recurrence was significantly (P=0.003) lower in the chemotherapy group than in the control group.\n The results of this study demonstrated the efficacy of adjuvant chemotherapy for colon cancer, i.e., combined chemotherapy that included the 5-FU oral anticancer drug HCFU.",
"Uracil-Tegafur (UFT), an oral fluorinated pyrimidine chemotherapeutic agent, has been used for adjuvant chemotherapy in curatively resected colorectal cancer patients. Past trials and meta-analyses indicate that it is somewhat effective in extending survival of patients with rectal cancer. The objective of this study was to perform a reappraisal of randomised clinical trials conducted in this field. We designed an individual patient-based meta-analysis of relevant clinical trials to examine the benefit of UFT for curatively resected rectal cancer in terms of overall survival (OS), disease-free survival (DFS), and local relapse-free survival (LRFS). We analysed individual patient data of five adjuvant therapy randomised clinical trials for rectal cancer, which met the predetermined inclusion criteria. These five trials had a combined total of 2091 patients, UFT as adjuvant chemotherapy compared to surgery-alone, 5-year follow-up, intention-to-treat-based analytic strategy, and similar endpoints (OS and DFS). In a pooled analysis, UFT had significant advantage over surgery-alone in terms of both OS (hazard ratio, 0.82; 95% confidence interval (CI), 0.70-0.97; P=0.02) and DFS (hazard ratio, 0.73; 95%CI, 0.63-0.84; P<0.0001). This individual patient-based meta-analysis demonstrated that oral UFT significantly improves both OS and DFS in patients with curatively resected rectal cancer.",
"A prospective controlled study, the 7th cooperative study of the Japanese Foundation for Multidisciplinary Treatment, was conducted to evaluate the usefulness of concomitant therapy with MMC + HCFU as a postoperative adjuvant therapy in patients with colorectal cancer who had undergone curative resection for a period of 2 years and 11 months from February, 1986. The Dukes B and C patients with colorectal cancer classified by macroscopic examination who had an intravenous MMC 6 mg/m2 on the day of operation and followed by oral HCFU for 12 months from 2 weeks after operation (Group X) were compared with patients who had operation only (Group Y). Some 978 patients with colon cancer and 713 patients with rectal cancer were enrolled in the study, 85 (5.0%) of whom were not eligible. The 5-year survival rate of Group X in colon cancer was 79.3% and that of Group Y was 76.4%: thus the survival rate of Group X was slightly better than that of Group Y, but no significant difference was found between the two groups. Subset analysis revealed that the survival rate of Group X in advanced cancer of stage III b + IV, according to the General Rules for Clinical and Pathological Studies on Cancer of the Colon, Rectum and Anus in Japan, was 62.4% and that of Group Y was 46.2%. Thus, the survival rate of Group X was significantly better than that of Group Y (logrank test: p = 0.035, generalized Wilcoxon test: p = 0.025). The disease-free survival rate was not significantly different between the groups with colon cancer and rectal cancer. The above results suggest that HCFU is useful for patients with a high risk of recurrence who had advanced colon cancer (stage III b + IV). However, additional prospective studies are required to verify them.",
"In the latter 1990s, adjuvant chemotherapy for completely resected Stage III colorectal cancer remained controversial in Japan. We conducted two independent randomized controlled trials in patients with Stage III colon and rectal cancer.\n Patients were randomly assigned to receive surgery alone or surgery followed by treatment with UFT (400 mg/m²/day), given for five consecutive days per week for 1 year. The primary endpoint was relapse-free survival (RFS), and the secondary endpoint was overall survival (OS).\n A total of 334 patients with colon cancer and 276 with rectal cancer were enrolled. The patients' characteristics were similar between the UFT group and the Surgery-alone group. There was no significant difference in RFS or OS in colon cancer. In rectal cancer, however, RFS and OS were significantly better in the UFT group than in the Surgery-alone group. The only grade 4 toxicity in the UFT group was diarrhea, occurring in one patient with colon cancer and one patient with rectal cancer.\n Postoperative adjuvant chemotherapy with UFT is successfully tolerated and improves RFS and OS in patients with Stage III rectal cancer. In colon cancer, the expected benefits were not obtained (hazard ratio = 0.89).",
"Gastric cancer in Western countries is often diagnosed in an advanced stage and prognosis is poor. We performed a randomised trial with pre-operative FAMTX vs. surgery alone in order to evaluate the effect of pre-operative chemotherapy on resectability and survival.\n Patients with proven adenocarcinoma of the stomach were randomised to receive four courses of chemotherapy using 5-Fluorouracil, doxorubicin and methotrexate (FAMTX) prior to surgery or to undergo surgery alone.\n Fifty-nine patients were randomised; 29 patients were allocated to the FAMTX regimen prior to surgery and 30 patients had surgery alone. Resectability rates were equal for both groups. Complete or partial response was registered in 32% of the FAMTX group. With a median follow-up of 83 months the median survival since randomisation is 18 months in the FAMTX group vs. 30 months in the surgery alone group (p=0.17).\n This trial could not show a beneficial effect of pre-operative FAMTX. Until large randomised studies prove otherwise, adequate surgery without delay is the best treatment for operable gastric cancer.",
"A prospective randomized trial (the second cooperative study) was conducted from July 1985 to December 1987 to investigate the benefits of postoperative adjuvant chemotherapy in patients for whom non-small cell lung cancer had been resected completely. Patients were randomly assigned either to a chemotherapy group (group A) treated postoperatively with CDDP (66 mg/m2 x 1), ADM (26 mg/m2 x 1) and UFT (8 mg/kg/day) during 6 months, or to a control group (group B) which had undergone surgery only. Three hundred and thirty-three resected cases were registered. Among them, 24 cases (7.2%) were excluded, because of incomplete resection (15), pathologically benign tumour (3), small cell lung cancer (2) and other factors (4). Three hundred and nine cases were eligible: 155 cases in group A (p-Stage I 93, II 19, III 43) and 154 in group B (I 109, II 10, III 35). The 5-year survival rate in group A was 61.8%, and that in group B 58.1%. The 5-year disease-free survival rate for each group was 61.8% and 57.4%, respectively. There were no significant differences in the 5-year survival between the two groups. However, since a significant difference was observed between the two groups regarding pathological lymph node metastasis (pN), the prognostic factors were adjusted using Cox's proportional hazard model. Thereafter the adjusted survival rate and disease-free survival rate for group A became significantly higher than for group B (P = 0.044 and P = 0.036, respectively). Thus, from these results, it is concluded that the role of surgery for non-small cell lung cancer still remains of primary importance, and postoperative adjuvant chemotherapy is effective to improve the results of surgery and prolong life of patients with non-small cell lung cancer.",
"To study the effect of adjuvant chemotherapy after curative hepatic resection in patients with hepatocellular carcinoma.\n A randomized controlled trial.\n A tertiary referral center.\n During a 54-month period, 142 patients with hepatocellular carcinoma underwent hepatic resection at 1 institution. Sixty-six patients who survived the operation and had no demonstrable evidence of residual disease on ultrasonographic examination and hepatic angiographic testing at 1 month after surgery agreed to participate in the study. The median follow-up time was 28.3 months.\n Thirty patients received a combination of intravenous epirubicin hydrochloride (8 doses of 40 mg/m2 each at 6-week intervals) and transarterial chemotherapy using an emulsion of iodized oil and cisplatin (3 courses with a maximum dose of 20 mL each at 2-month intervals). Thirty-six patients had no adjuvant treatment.\n Recurrence rate and disease-free survival.\n A total of 138 courses of intravenous epirubicin was given to the 30 patients. Sixty-one courses of transarterial chemotherapy were given to only 29 of the 30 patients assigned to the treatment group, because the hepatic artery in 1 patient was thrombosed. Six patients (20%) had chemotherapy-related complications with no mortality. Twenty-three of 30 patients in the treatment group and 17 of 36 patients in the control group had recurrences (P=.01). Patients who received adjuvant chemotherapy had a higher incidence of extrahepatic metastases (11 patients vs 5 patients; P=.03). The respective disease-free survival rates at 1, 2, and 3 years were 50%,36%, and 18% for the treatment group and 69%, 53%, and 48% for the control group (P=.04).\n In a group of patients who underwent curative resection of hepatocellular carcinoma, postoperative adjuvant chemotherapy using the present regimen was associated with more frequent extrahepatic recurrences and a worse outcome.",
"In 1992, preoperative radiotherapy was considered in France as the standard treatment for T3-4 rectal cancers. The present randomized trial compares preoperative radiotherapy with chemoradiotherapy.\n Patients were eligible if they presented a resectable T3-4, Nx, M0 rectal adenocarcinoma accessible to digital rectal examination. Preoperative radiotherapy with 45 Gy in 25 fractions during 5 weeks was delivered. Concurrent chemotherapy with fluorouracil 350 mg/m2/d during 5 days, together with leucovorin, was administered during the first and fifth week in the experimental arm. Surgery was planned 3 to 10 weeks after the end of radiotherapy. All patients should receive adjuvant chemotherapy with the same fluorouracil/leucovorin regimen. The primary end point of the trial was overall survival.\n A total of 733 patients were eligible. Grade 3 or 4 acute toxicity was more frequent with chemoradiotherapy (14.6% v 2.7%; P < .05). There was no difference in sphincter preservation. Complete sterilization of the operative specimen was more frequent with chemoradiotherapy (11.4% v 3.6%; P < .05). The 5-year incidence of local recurrence was lower with chemoradiotherapy (8.1% v 16.5%; P < .05). Overall 5-year survival in the two groups did not differ.\n Preoperative chemoradiotherapy despite a moderate increase in acute toxicity and no impact on overall survival significantly improves local control and is recommended for T3-4, N0-2, M0 adenocarcinoma of the middle and distal rectum.",
"A randomised clinical trial was performed in patients undergoing radical surgery for rectal cancer to compare the efficacy and toxicity of adjuvant postoperative radiation therapy (RT) to sequential RT and chemotherapy (CT) with 5-fluorouracil (5-FU) plus levamisole (LEV). The primary end point was overall survival (OS); secondary end points were disease-free survival (DFS), the rate of loco-regional recurrence, and treatment-related toxicity; the final results of this trial are reported.\n Patients in arm I underwent RT (50 Gy) in daily fractions of 2 Gy, 5 days/week for 5 weeks. Patients in arm II began with 5-FU (450 mg/sqm/day intravenous (i.v.) bolus, days 1-5) plus LEV (150 mg/day orally, days 1-3); postoperative RT was delivered during week 2 at the same dosage and schedule as in arm I. The other five cycles of CT (5-FU every 28 days and LEV every 15 days for the length of 5-FU administration) continued after the end of RT if clinical and hemato-biochemical parameters were in the normal range.\n From May 1992 to December 1998, 218 patients were enrolled into the randomised clinical trial (144 men, 74 women; age range: 28-75, median 64 years). The median follow-up time was 58.1 months (range: 1-3,271 days). No significant difference was observed between the two arms of treatment as regards OS and DFS (P = 0.18 and P = 0.66, respectively). Cox regression analysis for OS confirmed what was observed by univariate analysis for all variables except age. Older age (>60 years) and pathologic lymph-node involvement defined the subgroups with the worst prognosis. Cox regression analysis for DFS confirmed what was observed by univariate analysis for all variables: the only independent variable in predicting DFS was pathologic lymph-node involvement.\n Our findings suggest no difference in OS, loco-regional and distant site progressions of postoperative RT alone compared to sequential postoperative RT and CT; notably, this latter regimen was associated with higher toxicity which seriously impaired the patient's compliance to CT. The low loco-regional recurrence rate (9.2%) observed in our patients undergoing postoperative RT alone compared to similarly treated patients in previously performed clinical trials (20-25%) underline the role of radical surgery (mesorectal excision) coupled with a complete postoperative RT regimen. On the other hand, the similar efficacy of these two adjuvant modalities of treatment might be conditioned by both the low compliance (59%) to the CT regimen as well as the sequential, instead of concurrent, schedule of administration of RT and CT, which may have decreased further the expected efficacy of the combined regimen.\n Copyright 2003 Wiley-Liss, Inc.",
"Despite technical improvements that have minimized the morbidity and mortality of hepatic surgery, the long-term outcome of resection of hepatic metastases of colorectal cancer remains poor, with the majority of patients experiencing treatment failure in the liver. Because arterial chemotherapy regimens targeted to the liver have demonstrated high response rates, an intergroup trial of adjuvant therapy for patients undergoing hepatic resection of liver metastases from colorectal cancer was initiated.\n Patients with one to three potentially resectable metastases were randomized preoperatively to receive no further therapy (control arm, 56 patients) or postoperative hepatic arterial floxuridine combined with intravenous continuous-infusion fluorouracil (chemotherapy arm, 53 patients). After exclusion of patients identified as ineligible for the planned treatment at the time of surgery, there were 45 control patients and 30 on the chemotherapy arm. The study was powered to evaluate improvement in time to recurrence and hepatic disease-free survival, not overall survival.\n The 4-year recurrence-free rate was 25% for the control arm and 46% for the chemotherapy group (P =.04). The 4-year liver recurrence-free rate was 43% in the control group and 67% in the chemotherapy group (P =.03). The median survival of the 75 assessable patients was 49 months for the control arm and 63.7 months for the chemotherapy arm (P =.60). The median survival of all 109 patients was 47 months for the control arm compared with 34 months for the chemotherapy arm (P =.19)\n These data demonstrate that adjuvant intra-arterial and intravenous chemotherapy was beneficial in prolonging time to recurrence and pre-venting hepatic recurrence after hepatic resection of colorectal cancer.",
"To improve surgical results of potentially operable rectal cancer, the European Organization on Research and Treatment of Cancer conducted a two-arm randomized clinical trial to compare the efficiency of preoperative administration of radiotherapy, with or without 5-fluorouracil before radical surgery. Two hundred forty-seven eligible patients were admitted from November 1972 through April 1976. The overall survival observed in the group treated with preoperative radiotherapy appears to be better than in the group of patients where preoperative combined modality was administered. Five-year survival is 59% versus 46% with a marginal statistical significance of P = 0.06. Although the combined modality arm had a higher incidence of side effects and postoperative deaths, it had a greater effect than the radiotherapy-alone arm in controlling the disease process, mainly distant metastases to the liver with a result bordering on statistical significance (P = 0.07). The incidence of nonmalignant and intercurrent deaths were higher in the combined modality group, whereas deaths due to malignancy were higher in the radiotherapy-alone group. Observing more stringent selection in disease and patients' criteria, side effects and intercurrent deaths can be effectively reduced with further improvement in adjuvant therapy results.",
"This study had two major goals: (1) to assess the effectiveness of a regimen of fluorouracil (5-FU) plus levamisole plus leucovorin as postoperative surgical adjuvant therapy for patients with high-risk colon cancer, and (2) to evaluate 6 months versus 12 months of chemotherapy.\n Patients with poor-prognosis stage II or III colon cancer were randomly assigned to receive adjuvant chemotherapy with either intensive-course 5-FU and leucovorin combined with levamisole, or a standard regimen of 5-FU plus levamisole. Patients were also randomly assigned to receive either 12 months or 6 months of chemotherapy, which resulted in four treatment groups.\n Eight hundred ninety-one of 915 patients entered (97.4%) were eligible. The median follow-up duration is 5.1 years for patients still alive. There was a difference among the four treatment groups with respect to patient survival, and a significant duration-by-regimen interaction was observed. Specifically, standard 5-FU plus levamisole was inferior to 5-FU plus leucovorin plus levamisole when treatment was given for 6 months (5-year survival rate, 60% v 70%; P < .01).\n There was no significant improvement in patient survival when chemotherapy was given for 12 months compared with 6 months. When chemotherapy was given for 6 months, standard 5-FU plus levamisole was associated with inferior patient survival compared with intensive-course 5-FU plus leucovorin plus levamisole. These data suggest that 5-FU plus levamisole for 6 months should not be used in clinical practice, whereas 6 months of treatment with 5-FU plus leucovorin plus levamisole is effective."
] |
The results of this meta-analysis support the use of 5-FU based postoperative adjuvant chemotherapy for patients undergoing apparently radical surgery for non-metastatic rectal carcinoma. Available data do not allow us to define whether the efficacy of this treatment is highest in one specific TNM stage. The implementation of modern anti-cancer agents in the adjuvant setting is warranted to improve the results shown by this meta-analysis. Randomized trials of adjuvant chemotherapy for patients receiving preoperative neoadjuvant therapy are also needed in order to define the role of postoperative chemotherapy in the multimodal treatment of resectable rectal cancer.
|
CD004449
|
[
"16102099"
] |
[
"Recombinant activated factor VII in treatment of bleeding complications following hematopoietic stem cell transplantation."
] |
[
"Bleeding is a common complication following hematopoietic stem cell transplantation (HSCT) and standard hemostatic treatment is often ineffective. We conducted a multicentre, randomized trial of the efficacy and safety of activated recombinant factor VII (rFVIIa, NovoSeven) in the treatment of bleeding following HSCT.\n 100 patients with moderate or severe bleeding (52 gastrointestinal; 26 hemorrhagic cystitis; seven pulmonary; one cerebral; 14 other) were included from days +2 to +180 post-transplant (97 allogeneic; three autologous) to receive seven doses of rFVIIa (40, 80 or 160 microg kg(-1)) or placebo every 6 h. The primary efficacy endpoint was the change in bleeding score between the first administration and 38 h.\n No significant effect of increasing rFVIIa dose was observed on the primary endpoint. A post hoc analysis comparing each rFVIIa dose with placebo showed that 80 microg kg(-1) rFVIIa improved the bleeding score at the 38 h time point (81% vs. 57%, P = 0.021). This effect was not seen at 160 microg kg(-1). There were no differences in transfusion requirements across dose groups. There was no trend in the type or number of severe adverse events observed. Six thromboembolic events were observed in the active treatment groups: three during, and three following the 96-h observation period.\n Despite no overall effect of rFVIIa treatment on primary endpoint, post hoc analysis showed an improvement in the control of bleeding for 80 microg kg(-1) rFVIIa vs. standard hemostatic treatment. The heterogeneity of the population may have contributed to the lack of an increasing effect with increased dose. Further trials should focus upon identifying the patient populations that may benefit from treatment with rFVIIa."
] |
Although the main conclusion should be the need for further randomised controlled trials, we conclude that both rFVIIa and aPCC can be used to treat bleeding in haemophiliacs with inhibitors.
|
CD002903
|
[
"14736444"
] |
[
"Effect of rate or rhythm control on quality of life in persistent atrial fibrillation. Results from the Rate Control Versus Electrical Cardioversion (RACE) Study."
] |
[
"We studied the influence of rate control or rhythm control in patients with persistent atrial fibrillation (AF) on quality of life (QoL).\n Atrial fibrillation may cause symptoms like fatigue and dyspnea. This can impair QoL. Treatment of AF with either rate or rhythm control may influence QoL.\n Quality of life was assessed in patients included in the Rate Control Versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE) study (rate vs. rhythm control in persistent AF). Rate control patients (n = 175) were given negative chronotropic drugs and oral anticoagulation. Rhythm control patients (n = 177) received serial electrocardioversion, antiarrhythmic drugs, and oral anticoagulation, as needed. Quality of life was studied using the Short Form (SF)-36 health survey questionnaire at baseline, one year, and the end of the study (after 2 to 3 years of follow-up). At baseline, QoL was compared with that of healthy control subjects. Patient characteristics related to QoL changes were determined.\n Mean follow-up was 2.3 years. At baseline, QoL was lower in patients than in age-matched healthy controls. At study end, under rate control, three subscales of the SF-36 improved. Under rhythm control, no significant changes occurred compared with baseline. At study end, QoL was comparable between both groups. The presence of complaints of AF at baseline, a short duration of AF, and the presence of sinus rhythm (SR) at the end of follow-up, rather than the assigned strategy, were associated with QoL improvement.\n Quality of life is impaired in patients with AF compared with healthy controls. Treatment strategy does not affect QoL. Patients with complaints related to AF, however, may benefit from rhythm control if SR can be maintained."
] |
Electrical cardioversion (rhythm control) led to a non-significant increase in stroke risk but improved three domains of quality of life.
|
CD002862
|
[
"8605125",
"7052115"
] |
[
"Induction of labour: a randomised clinical trial of amniotomy versus amniotomy with oxytocin infusion.",
"Induction of labour: a comparison of a single prostaglandin E2 vaginal tablet with amniotomy and intravenous oxytocin."
] |
[
"To compare two methods of induction of labour-amniotomy with oxytocin infusion versus amniotomy alone.\n Prospective randomised clinical trial.\n The department of obstetrics in a Swedish central hospital.\n One hundred and ninety-six pregnant women with indication for induction of labour at term and a favourable cervix (modified Bishop score > or = 6).\n The women were randomised to amniotomy followed by oxytocin infusion after 1 h (group A, n = 98) or amniotomy alone (group B, n = 98). If labour had not ensued on the following morning, after approximately 24 h, the women in group B were given an oxytocin infusion.\n Induction-delivery interval, duration of labour, time spent in delivery ward, oxytocin use, maternal and neonatal clinical outcome.\n Amniotomy combined with early oxytocin infusion resulted in shorter induction-delivery interval (median 6.0 h; 95% confidence interval (CI) 5.0 to 6.5 h) than amniotomy alone (median 9.0 h; 95% CI 7.5 to 10.0 h). This was due to a shorter latent period in the former group (median 2.3 h; 95% CI 2.0 to 3.0 h) compared to the latter (median 4.3 h; 95% CI 3.0 to 5.5 h). The duration of labour stages 1 and 2 were similar in both groups. The time spent in the delivery ward was slightly reduced for women managed by amniotomy alone (median 5.0 h; 95% CI 4.5 to 6.0 h) compared with those managed by the combination of amniotomy and oxytocin infusion (median 6.0 h; 95% CI 5.0 to 6.5 h). Eighty-seven percent in group A and 32% in group B were given oxytocin, and the total oxytocin infusion time was nearly five times longer in group A. No other important effect on maternal or fetal outcomes was demonstrated.\n With regard to safety the results do not warrant recommending either type of labour induction. The minor differences observed between the induction groups justify an individual management policy, with attention paid to both the indication for induction of labour and the woman's choice.",
"In a randomized controlled study of 100 women of low parity and favourable induction features, induction of labour by means of a single vaginal tablet containing 3 mg of prostaglandin E2 (PGE2) was compared with the conventional method of amniotomy and intravenous oxytocin. Four of the patients (8%) who received the prostaglandin tablet required additional intravenous oxytocin to achieve delivery. The prostaglandin group had a longer mean overall induction-delivery interval but a shorter amniotomy-delivery interval than the oxytocin group. One patient in the PGE2 group and two in the oxytocin group required caesarean section. The PGE2 treated patients expressed a higher level of satisfaction with their method of induction, they required less analgesia, had less blood loss at delivery and their babies had a lower incidence of neonatal jaundice."
] |
Data are lacking about the value of amniotomy alone for induction of labour. While there are now other modern methods available for induction of labour (pharmacological agents), there remain clinical scenarios where amniotomy alone may be desirable and appropriate, and this method is worthy of further research. This research should include evaluation of the appropriate time interval from amniotomy to secondary intervention, women and caregivers' satisfaction and economic analysis.
[Note: the two citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]
|
CD008888
|
[
"11591548"
] |
[
"Application and validation of a computerized cough acquisition system for objective monitoring of acute cough: a meta-analysis."
] |
[
"The purpose of the meta-analysis was to understand the antitussive effect of treatment with dextromethorphan hydrobromide, 30 mg, vs placebo over a 3-h treatment period in patients with cough due to uncomplicated upper respiratory tract infection (URTI), and to show that the computerized system for acquisition and analysis of cough sound was consistent and reproducible across the individual studies.\n The six studies used for the meta-analysis were randomized, double-blind, parallel-group, single-dose, placebo-controlled studies with a 3-h postdose cough evaluation period.\n One study was conducted in Durban, South Africa, and five studies were conducted in Bombay, India. Four studies took place in clinics, and two studies were in-home studies.\n Seven hundred ten adult patients with cough due to uncomplicated URTI who were otherwise healthy and who satisfied the inclusion/exclusion criteria for the meta-analysis. Measurements and results: For each patient, a standard baseline was calculated pretreatment, then a 3-h continuous cough recording was made after treatment was initiated. Five efficacy variables were measured in 30-min intervals: cough bouts, cough components, cough effort, cough intensity, and cough latency. The meta-analysis showed consistent results across most of the studies for each of the efficacy variables. It demonstrated significantly greater overall reductions in cough bouts, cough components, and cough effort, and an increase in cough latency for patients treated with dextromethorphan hydrobromide, 30 mg, vs those treated with placebo.\n The results of a meta-analysis of the six clinical studies show that the antitussive effect of a single dose of dextromethorphan hydrobromide, 30 mg, has been established. The consistent nature of the results shows that the computerized cough acquisition and analysis system is a valid and reproducible methodology for evaluating cough associated with URTI."
] |
There is currently no evidence to support the use of ICS for treatment of subacute cough in children. However, this systematic review is limited by the small number of studies available for analysis and the size, quality and design of these studies. Further well-designed RCTs are required to support or refute the efficacy of treatment with ICS in children with subacute cough.
|
CD006072
|
[
"3627875",
"6823418",
"3292250",
"2645569",
"8694013",
"6423796",
"8241636"
] |
[
"Taurine supplementation of a premature formula improves fat absorption in preterm infants.",
"Feeding the low-birth-weight infant: I. Taurine and cholesterol supplementation of formula does not affect growth and metabolism.",
"Development of the nervous and cardiovascular systems in low-birth-weight infants fed a taurine-supplemented formula.",
"Randomized trial of taurine supplementation for infants less than or equal to 1,300-gram birth weight: effect on auditory brainstem-evoked responses.",
"Randomized outcome trial of human milk fortification and developmental outcome in preterm infants.",
"Effect of taurine supplementation on hepatic function during short-term parenteral nutrition in the premature infant.",
"Influence of dietary taurine on vitamin D absorption."
] |
[
"The predominance of taurine (Tau) conjugated over glycine conjugated bile acids in infants fed human milk as opposed to those on formulas without added Tau could account for a more complete absorption of fat. Fifteen low birth weight infants were randomized to either Enfamil Premature or to Enfamil Premature added with 40 mumol/dl of Tau and compared to a third group made up of nine low birth weight infants fed their own mother's preterm milk. Formulas and human milk were fed according to tolerance and constituted the sole nutrition for 3 months. A metabolic study was carried out at 3 wk of age and control of growth was done periodically. Urinary Tau excretion (mumol/dl) was very low (p less than 0.001) in the group fed Enfamil Premature (0.3 +/- 0.1) when compared to the values obtained in infants supplemented with Tau (51.6 +/- 12.5) and in those on human milk (36.3 +/- 7.9). Infants supplemented with Tau (92.5 +/- 1.2) had a coefficient of fat absorption which was higher (p less than 0.05) than the unsupplemented group (87.5 +/- 7.9) and comparable to the human milk-fed group (91.6 +/- 1.4). The effect was more pronounced on the saturated fatty acids and varied inversely with their individual water solubility. There was no effect of Tau on nitrogen retention and growth was identical in the three groups. These data show that the addition of Tau to formula had no effect on growth but improved the absorption of fat especially saturated fatty acids which require higher concentrations of bile acids to form mixed micelles.",
"Taurine and cholesterol are constituents of human milk that are present in smaller amounts in infant formulas. Infants fed such formulas have lower plasma and urine concentrations of taurine and of serum total cholesterol. In the present investigation, in infants of 31 to 36 weeks gestational age, the effects of supplementing a 1.5 g/100 mL whey-predominant formula with taurine alone or with taurine plus cholesterol were examined. Infants fed the supplemented formula were compared with infants fed the unsupplemented formula and with infants fed pooled, expressed human milk (185 mL/kg/d). Approximately 45% of the human milk provided to each infant was that of the infant's mother (35% pasteurized and 10% fresh). From the time of reaching a weight of 2,400 g to 4 months of age the last group of infants was fed ad libitum. No consistent statistically significant differences in growth, as measured by rate of gain in crown-rump length, crown-heel length, or head circumference, were observed. There was a tendency, however, for the formula-fed infants to gain weight more slowly before reaching 2,400 g and to gain weight more quickly after a weight of 2,400 g was attained to 4 months of age. No differences in concentrations of BUN, total serum proteins, or acid-base status were observed among the formula-fed groups. The concentration of BUN increased in the formula-fed groups compared with the group fed human milk during the last half of the study. The formula-fed infants tended to have higher total serum proteins and to be slightly more acidotic than the infants fed human milk prior to discharge at a weight of 2,400 g but not thereafter. Thus, infants fed 185 mL/kg/d gained weight at rates comparable to those for fetuses of the same gestational age. Supplementation of formulas with taurine or taurine plus cholesterol did not produce changes in growth or general metabolism discernible under the present experimental conditions.",
"An adapted cow's milk formula with or without supplemental taurine (480 mumol/l) was fed for 16 weeks to 20 low-birth-weight infants. In the 2nd and 16th weeks of life, respectively, the following parameters were determined: growth, sonography of heart and brain, ECG, EEG, neurological development and the taurine concentration of plasma and urine. None of the parameters investigated was influenced by taurine supplementation except the urinary taurine excretion. At least according to these data, the addition of taurine to whey-predominant infant formulae seems to be unnecessary for the development of heart and brain function in low-birth-weight infants.",
"Taurine may be important to the developing eye and brain of the small preterm infant. A blinded randomized trial was conducted to determine whether taurine supplementation of healthy infants of less than or equal to 1,300 g birth weight until their discharge from the hospital increases their growth rate, neurobehavioral development, electroretinographic development, or maturation of auditory brainstem-evoked responses. Infants were fed with Similac Special Care as desired, which was prepared to contain less than 5 mg/L of taurine or 45 mg/L of taurine, a concentration similar to that of human milk. Infants who did not receive taurine supplementation (n = 19) and those who did (n = 18) were similar with respect to condition at study entry, caloric intake, and growth rates throughout the study, and electroretinographic findings and scores on the Brazelton Behavioral Assessment Scale at 37 weeks' postmenstrual age. Infants who received taurine supplementation had greater overall plasma taurine concentrations. The group receiving taurine supplementation also had more mature auditory-evoked responses at 37 weeks' postmenstrual age with a modest (0.2 to 0.5 ms) but consistent reduction (P less than .05) in the interval between stimulus and response at two different stimulation rates. Although further study is needed, taurine intake appears to influence auditory system maturation of preterm infants.",
"Despite potential benefits, human milk may fail to meet preterm infants' nutrient requirements. We tested the hypothesis that fortified breast milk, fed alone or with preterm formula, would improve neurodevelopment and growth at 18-mo follow-up without adverse short-term clinical or biochemical consequences. Two hundred seventy-five preterm infants from two medical centers (birth weight < 1850 g; mean gestation 29.8 +/- 2.7 wk) whose mothers chose to provide breast milk were randomly assigned to receive for a mean of 39 d a multinutrient fortifier or control supplement containing phosphate and vitamins. Breast milk comprised 47.6% and 46.4% of enteral intake in fortified and control groups, respectively; preterm formula supplements were used when insufficient breast milk was available. Overall, there were no significant growth advantages with fortification; although, when breast milk exceeded 50% of intake, fortification promoted faster weight gain (an advantage of 1.6 g.kg-1.d-1; 95% CI: 0.1, 3.1; P < 0.05). Compared with control infants, the fortified group showed 1) higher plasma urea from week 2 (P = 0.04), 2) higher plasma calcium (mean 2.34 +/- 0.01 compared with 2.27 +/- 0.02 mmol/L; P = 0.003), 3) a greater rise in alkaline phosphatase by week 6 (P = 0.04), 4) more clinical infections (suspected plus proven; 43% compared with 31%, P = 0.04), 5) a nonsignificantly increased incidence of necrotizing enterocolitis (5.8% compared with 2.2%, P = 0.12), and 6) higher white cell and platelet counts. Developmental scores at 18 mo were slightly but not significantly higher in the fortified group. This study confirmed that breast milk fortifiers can improve short-term growth (when breast milk intakes are high); but beneficial effects on long-term development remained unproven. Future research is required to evaluate potential adverse consequences and explore more optimal fortification strategies.",
"To evaluate the potential role of taurine deficiency in the pathogenesis of parenteral nutrition-induced cholestasis, 20 premature (less than 34 weeks AGA) infants were randomized to receive parenteral nutrition with and without taurine (10.8 mg/kg/day) during the first 10 days of life. Birth weight, gestational age, and protein and caloric intake were similar in both groups. Plasma taurine levels and hepatic function were assessed before the study began (3 +/- 1 days of age), at 5 +/- 1 days of age, and at 9 +/- 1 days of age. Although plasma taurine levels were significantly greater at 5 +/- 1 and 9 +/- 1 days of age (p = 0.009) in the group receiving supplementation, no differential effect on hepatocellular function could be detected during this short period of time. A decrease in plasma ammonia (p = 0.001), alanine aminotransferase (ALT) (p = 0.036), gamma-glutamyltranspeptidase (GGTP) (p = 0.05), 5'-nucleotidase (5'N) (p = 0.001), and bile salt concentrations was noted in both groups, indicating the rapid maturation of hepatic function even in the presence of parenteral nutrition during the first 10 days of life.",
"To evaluate the influence of dietary taurine supplementation on vitamin D absorption, we studied three groups of infants: 21 (11 preterm) were fed a taurine-free formula, 21 (10 preterm) were fed a taurine-supplemented formula (50 mg/100 g of powder) and 20 (9 preterm) were fed human, not heat-treated milk. Taurine, total bile acids, glyco-(GBA) and tauro-(TBA) conjugated bile acids, 25-hydroxyvitamin D3 (25OHD3) and 1,25-dihydroxyvitamin D3 (1,25OH2D3) were determined in all infants at birth in blood cord and at one and three months of life. In preterm infants fed a taurine-free formula, we found lower plasma taurine levels than in infants of other groups at one and three months of life. In these infants, GBA predominated, with a G/T ratio of 1.1 and 1.4 at one and three months of life, whereas in all other infants TBA predominated with a G/T ratio always < 1. Also, 25OHD3 and 1,25OH2D3 levels were significantly lower in preterm infants fed a taurine-free formula than in infants fed a taurine-enriched formula or human milk. Term infants fed a taurine-free formula did not show differences in the parameters studied in comparison to infants of other groups. Low taurine dietary intake appears to compromise vitamin D absorption in preterm infants, and therefore taurine supplementation of preterm infant formulas should be encouraged."
] |
Despite that lack of evidence of benefit from randomised controlled trials, it is likely that taurine will continue to be added to formula milks and parenteral nutrition solutions used for feeding preterm and low birth weight infants given the putative association of taurine deficiency with various adverse outcomes. Further randomised controlled trials of taurine supplementation versus no supplementation in preterm or low birth weight infants are unlikely to be viewed as a research priority, but there may be issues related to dose or duration of supplementation in specific subgroups of infants that merit further research.
|
CD006411
|
[
"20841574"
] |
[
"Game-based versus traditional case-based learning: comparing effectiveness in stroke continuing medical education."
] |
[
"To evaluate family physicians' enjoyment of and knowledge gained from game-based learning, compared with traditional case-based learning, in a continuing medical education (CME) event on stroke prevention and management.\n An equivalence trial to determine if game-based learning was as effective as case-based learning in terms of attained knowledge levels. Game questions and small group cases were developed. Participants were randomized to either a game-based or a case-based group and took part in the event.\n Ontario provincial family medicine conference.\n Thirty-two family physicians and 3 senior family medicine residents attending the conference.\n Participation in either a game-based or a case-based CME learning group.\n Scores on 40-item immediate and 3-month posttests of knowledge and a satisfaction survey.\n Results from knowledge testing immediately after the event and 3 months later showed no significant difference in scoring between groups. Participants in the game-based group reported higher levels of satisfaction with the learning experience.\n Games provide a novel way of organizing CME events. They might provide more group interaction and discussion, as well as improve recruitment to CME events. They might also provide a forum for interdisciplinary CME. Using games in future CME events appears to be a promising approach to facilitate participant learning."
] |
The findings of this systematic review neither confirm nor refute the utility of games as a teaching strategy for health professionals. There is a need for additional high-quality research to explore the impact of educational games on patient and performance outcomes.
|
CD004618
|
[
"15679563",
"15367178",
"18598837",
"2725163",
"11879929",
"14568795",
"9088679",
"12122630",
"11589975",
"17184455",
"15126742"
] |
[
"Topical quinolone vs. antiseptic for treating chronic suppurative otitis media: a randomized controlled trial.",
"Oral quinolones in hospitalized patients: an evaluation of a computerized decision support intervention.",
"A single topical agent is clinically equivalent to the combination of topical and oral antibiotic treatment for otitis externa.",
"Preoperative therapeutic considerations in chronic suppurative otitis media.",
"Treatment of chronic suppurative otitis media with ofloxacin in hydroxypropyl methylcellulose ear drops: a clinical/bacteriological study in a rural area of Malawi.",
"Evaluation of topical povidone-iodine in chronic suppurative otitis media.",
"A double blind, prospective trial of topical ciprofloxacin versus normal saline solution in the treatment of otorrhoea.",
"[Efficacy of topical ciprofloxacin and tobramycin in combination with dexamethasone in the treatment of chronic suppurative otitis media].",
"A comparison of cortisporin and ciprofloxacin otic drops as prophylaxis against post-tympanostomy otorrhea.",
"Prospective randomised single-blind controlled trial of glacial acetic acid versus glacial acetic acid, neomycin sulphate and dexamethasone spray in otitis externa and infected mastoid cavities.",
"Acute otitis externa: efficacy and tolerability of N-chlorotaurine, a novel endogenous antiseptic agent."
] |
[
"To compare a topical quinolone antibiotic (ciprofloxacin) with a cheaper topical antiseptic (boric acid) for treating chronic suppurative otitis media in children.\n Randomized controlled trial.\n A total of 427 children with chronic suppurative otitis media enrolled from 141 schools following screening of 39 841 schoolchildren in Kenya. Intervention Topical ciprofloxacin (n = 216) or boric acid in alcohol (n = 211); child-to-child treatment twice daily for 2 weeks.\n Resolution of discharge (at 2 weeks for primary outcome), healing of the tympanic membrane, and change in hearing threshold from baseline, all at 2 and 4 weeks.\n At 2 weeks, discharge was resolved in 123 of 207 (59%) children given ciprofloxacin, and in 65 of 204 (32%) given boric acid (relative risk 1.86; 95% CI 1.48-2.35; P < 0.0001). This effect was also significant at 4 weeks, and ciprofloxacin was associated with better hearing at both visits. No difference with respect to tympanic membrane healing was detected. There were significantly fewer adverse events of ear pain, irritation, and bleeding on mopping with ciprofloxacin than boric acid.\n Ciprofloxacin performed better than boric acid and alcohol for treating chronic suppurative otitis media in children in Kenya.",
"To determine whether a computerized decision support system could increase the proportion of oral quinolone antibiotic orders placed for hospitalized patients.\n Prospective, interrupted time-series analysis.\n University hospital in the south-eastern United States.\n Inpatient quinolone orders placed from 1 February 2001 to 31 January 2003.\n A web-based intervention was deployed as part of an existing order entry system at a university hospital on 5 February 2002. Based on an automated query of active medication and diet orders, some users ordering intravenous quinolones were presented with a suggestion to consider choosing an oral formulation.\n The proportion of inpatient quinolone orders placed for oral formulations before and after deployment of the intervention.\n There were a total of 15 194 quinolone orders during the study period, of which 8962 (59%) were for oral forms. Orders for oral quinolones increased from 4202 (56%) before the intervention to 4760 (62%) after, without a change in total orders. In the time-series analysis, there was an overall 5.6% increase (95% CI 2.8-8.4%; P < 0.001) in weekly oral quinolone orders due to the intervention, with the greatest effect on nonintensive care medical units.\n A web-based intervention was able to increase oral quinolone orders in hospitalized patients. This is one of the first studies to demonstrate a significant effect of a computerized intervention on dosing route within an antibiotic class. This model could be applied to other antibiotics or other drug classes with good oral bioavailability.",
"To demonstrate clinical equivalence (statistical noninferiority) of topical ciprofloxacin and hydrocortisone (CHC, Cipro HC) and topical neomycin/polymyxin b/hydrocortisone (NPH, Cortisporin) with systemic amoxicillin (AMX, Amoxil), for treatment of acute otitis externa (AOE).\n Randomized, active-control, observer-blind, multicenter trial.\n Altogether, 206 patients were enrolled (CHC, 106; NPH + AMX, 100). Patients were > or =1 year of age, had AOE >2 days with at least mild symptoms, and gave informed consent. All were evaluable for safety, and 151 were evaluable for efficacy.\n Ciprofloxacin and hydrocortisone 3 drops twice daily for 7 days (adults and children) or NPH 4 drops (adults) or 2 drops (children) with AMX 250 mg (adults and children) 3 times daily for 10 days, as directed in approved product labeling.\n The primary efficacy variable was response to therapy 7 days after treatment ended (test of cure). Secondary variables included time to end of pain, symptom scores (otalgia and tenderness) and microbiological eradication. Noninferiority was declared if the lower confidence limit around the measurement difference was above -10 (nearer zero).\n Response to therapy was higher for CHC (95.71% vs 89.83%) but was statistically noninferior (lower confidence limit, -4.98) to NPH + AMX. Median time to end of pain was 6 days for both groups. Noninferiority was declared for symptom scores at all measurement periods and for microbiological eradication. No serious adverse events related to treatment were reported.\n Ciprofloxacin and hydrocortisone is clinically equivalent to NPH + AMX for the treatment of AOE in adults and children. However, low systemic exposure, absence of ototoxicity, and less frequent dosing clearly favor Cipro HC.",
"The present randomized, prospective study of 119 cases of chronic suppurative otitis media compares the effectiveness of inexpensive, atoxic, nonallergenic disinfectants applied locally, to that of a number of occasionally toxic antimicrobial chemotherapeutic agents, administered systemically. Systemic treatment resulted in a cure rate of 53.5% (SEp = 5.9%) while ototopical treatment resulted in a 39.5% cure rate (SEp = 7%). Eradication of pathogens or colonization by a nonpathogen occurred in 50.7% (SEp = 5.9%) with systemic treatment, and in 39.5% (SEp = 7%) with ototopical treatment. Bacteriological modification was 2.5 times more frequent with systemic treatment than with ototopical treatment. No recurrences were noted with ototopical treatment, while 13% to 36% recurrence rates were noted in various subgroups of cases treated systemically. Cure rates achieved with particular drug regimens (administration based on sensitivity tests in vitro) were: Azactam 25% (5%-57% confidence limits), sulfamethoxazole plus trimethoprim 58.6% (38%-76%), ciprofloxacin 87.5% (47%-99%), ciprofloxacin plus metronidazole 90% (55%-99%). Cure rates with other drugs were inconclusive because of the limited number of observations.",
"Chronic suppurative otitis media in young children is a major problem in Africa, with socio-economic consequences at a later age. Common treatment regimens with antibiotics are expensive and often not practically feasible. Therefore, a project was started to develop a low-cost and effective treatment in a rural area of Malawi by studying the clinical efficacy of an inexpensive application regimen of ofloxacin (0.075%) in hydroxypropyl methylcellulose (1.5%) ear drops. In earlier studies with this treatment regimen, it was possible to cure approximately 70% of ears. The aim of this study was to find out whether the bacteriological spectrum cultured from wet ears before and after treatment, and patterns of resistance to antibiotics, played a role in the percentage of cures. Patients with long-standing chronic suppurative otitis media were clinically assessed and treated with suction cleaning and instillation of ear drops on days 1, 3, 7 and 10. Bacterial swabs were taken for culture and sensitivity tests for ofloxacin were on days 1 and 10 from the ears that were still discharging. After 21 weeks, the ears were assessed again clinically. Clinical cure was considered to be complete cessation of otorrhea. Ninety of 104 tested patients (124 ears) completed the study. About 73% of the ears had become dry by day 10. This dropped to 42% after 21 weeks. Before treatment, most ears (91%) harbored fecal bacteria, Proteus mirabilis (74%) and enterococci (60%) being the most frequently isolated microbes. The second group of frequently cultured bacteria were water bacteria e.g. Pseudomonas species and other non-fermenters (69%), whereas the classical otitis media pathogens were detected only in 15% of ears. Before treatment, 9.7% of strains were resistant to ofloxacin, most (30/35) of which were cultured from ears that were eventually cured. After treatment, fecal and water bacteria were still the most frequently found, with 36% new strains and an overall sensitivity to ofloxacin of 58%. Bacterial resistance did not appear to play an important role in the outcome of treatment. These data rather suggest a very high risk of infection due to poor hygiene conditions. Medical treatment can only have a longer-lasting effect if accompanied by community-based programs that focus on improvement of hygiene. A public health approach is necessary alongside a medical approach for the management of CSOM.",
"To evaluate if povidone-iodine (PVP-I) can be used topically in the treatment of chronic suppurative otitis media-tubotympanic disease and to compare it with ciprofloxacin hydrochloride ear drops.\n Prospective double-blind randomized study.\n Academic tertiary medical center.\n Forty patients with chronic suppurative otitis media were randomized into 2 groups.\n One group (19 patients) received 5% PVP-I ear drops, while the other group (21 patients) received 0.3% ciprofloxacin ear drops. Both were administered topically, 3 drops 3 times daily for 10 days. These patients were followed up at weekly intervals for up to 4 weeks after commencing therapy.\n Clinical improvement at the end of study was 88% in the PVP-I group and 90% in the ciprofloxacin group. The most commonly isolated organism was Pseudomonas aeruginosa. In vitro resistance to ciprofloxacin was seen in 17% of organisms, while no resistance was seen for PVP-I.\n To our knowledge, this is the first study to evaluate the efficacy of PVP-I as a topical agent in the treatment of chronic suppurative otitis media. The results show that clinically, topical PVP-I is as effective as topical ciprofloxacin, with a superior advantage of having no in vitro drug resistance. Also, there is an added benefit of reduced cost of therapy.",
"The clinical and bacteriological efficacy of topical ciprofloxacin in saline solution and a saline solution without antibiotics, for the treatment of otorrhoea, was assessed. Fifty affected ears which had an acute exacerbation of chronic otitis media with tympanic membrane perforation were included in this study. Only 35 ears completed the study. Both medications were randomly given to patients. Therapeutic efficacy was evaluated on the seventh day of treatment. A favourable clinical response was observed in 89.5% of the ciprofloxacin-treated group and in 43.8% of the saline-treated group, respectively (P < 0.005). Bacteriological eradication was also observed to be higher in the ciprofloxacin-treated group (P < 0.005). From these preliminary results, topical ciprofloxacin appears to be effective in curing the acute phase of chronic otitis media.",
"To evaluate the efficacy of topical ciprofloxacin and tobramycin with and without topical dexamethasone in the treatment of chronic suppurative otitis media without cholesteatoma.\n The study included 103 ears of 80 patients (49 males, 31 females; mean age 31 years; range 18 to 60 years) with chronic suppurative otitis media without cholesteatoma. The patients were randomly divided into four groups to receive topical applications of either ciprofloxacin and tobramycin alone, or in combination with dexamethasone. Cultures were obtained from the ears preoperatively and 24 hours after treatment.\n Aerobic bacteria were isolated in 94.1% of patients before the treatment, the most common being Pseudomonas aeruginosa (38.9%). With dexamethasone, the clinical response for ciprofloxacin and tobramycin increased from 80% to 90% and from 70% to 75%, respectively, but this improvement was not significant (p > 0.03). Addition of dexamethasone to ciprofloxacin decreased the recovery period from 14 days to seven days, whereas no change (7 days) was observed with tobramycin.\n The efficacy of ciprofloxacin and tobramycin were similar in the treatment of chronic suppurative otitis media. Addition of dexamethasone to ciprofloxacin decreased the treatment period.",
"Myringotomy and tube insertion, a common pediatric surgical procedure, is frequently complicated by purulent otorrhea. Many otolaryngologists routinely use topical antibiotics as prophylaxis against post-tympanostomy otorrhea. The aminoglycosides (neomycin sulfate, tobramycin and gentamicin) contained in commonly used topical antibiotics as well as components of the solutions have been shown to be ototoxic in animal studies. Although little reported evidence of ototoxicity in humans exists, sporadic reports of sensorineural hearing loss linked to topical antibiotic use do exist, and the potential for sensorineural hearing loss must be considered. The purpose of this study is to compare the rate of post-tympanostomy otorrhea in a double-blinded randomized trial using either topical Ciprofloxacin, with no reported ototoxicity, or Cortisporin as prophylaxis. One hundred patients (200 ears) between ages 7 months and 11 years with a diagnosis of recurrent otitis media or chronic otitis media undergoing tympanostomy tube insertion were randomized into two equal groups. Three drops of either drop A or B were placed into each ear at the time of tube insertion and then three times daily for 3 days. Patients were examined at 3 weeks and details of otorrhea were obtained. The rate of otorrhea was analyzed using chi-square. The overall rate of otorrhea was 39 ears (19.5%), 17 (17%) ears for the Cortisporin group and 22 (22%) for the Ciprofloxacin group. The difference in rate of otorrhea was not statistically significant (P=0.372, 95% confidence interval equals -6-16%). Our data suggest that topical Cortisporin offers no benefit over Ciprofloxacin for post-operative otorrhea prophylaxis. Therefore we recommend topical quinolone prophylaxis, which should eliminate concerns about ototoxicity, without sacrificing efficacy.",
"The literature reports the merits of antibacterial, antibiotic and steroid agents in treating otological infections but no controlled clinical trial has directly compared 2% glacial acetic acid (EarCalm; Stafford-Miller Ltd, Brentford, UK) against 2% glacial acetic acid, 0.1% dexamethasone and 3250 U/ml of neomycin sulphate (Otomize; Stafford-Miller Ltd) in the treatment of otitis externa and infected mastoid cavities.\n Prospective, single-blind randomised controlled trial.\n Outpatients, Derby Royal Infirmary, Derby, UK.\n Emergency and GP referrals with acute otitis externa (n = 53) and infected mastoid cavities (n = 56).\n Otoscopy was performed at initial randomisation and then at 2 and 4 weeks, the ear assessed for active and inactive disease.\n Patients with active otitis externa, 71% (15/21) resolved with glacial acetic acid, dexamethasone and of neomycin sulphate after 2 weeks, increasing to 86% (18/21) after 4 weeks treatment. Patients on glacial acetic acid had only 38% (12/32) resolution after 4 weeks (P < 0.0005). Two per cent glacial acetic acid, dexamethasone and neomycin sulphate resolved only 30% (8/27) of infected mastoid cavities compared to only 10% (3/29) on glacial acetic acid (P < 0.07). A further 2 weeks treatment this increased to 67%, (18/27) with glacial acetic acid, dexamethasone and neomycin sulphate and 48% (14/29) with glacial acetic acid. These results are not statistically significant.\n Glacial acetic acid, dexamethasone and neomycin sulphate is significantly more effective in treating otitis externa when compared with glacial acetic acid. This effect failed to be significant in the infected mastoid cavities group. We therefore recommend that in conjunction with aural toilet, antibiotic/steroid combination is more effective than an antibacterial agent for otitis externa. Larger numbers of infected mastoid cavities are required to be studied.",
"The study's objective was to test the tolerability and efficacy of the endogenous antiseptic N-chlorotaurine (NCT) in comparison with a standard clinical treatment according to a phase IIb clinical trial protocol.\n The antimicrobial agent NCT was compared with the antibiotic component drops Otosporin (containing neomycin, polymyxin B, and hydrocortisone) for topical treatment of acute otitis externa in a randomized and rater-blinded clinical study.\n Fifty patients suffering from acute otitis externa were divided into two groups according to a randomized list. The test group was treated with 1 mL of 1% aqueous NCT solution, the reference group with 1 mL of Otosporin. The substances were applied to the external ear canal at one daily session until the signs of infection disappeared. Efficacy and tolerability were evaluated daily by visual analogue scale and a six-step infection score. In addition, smears were analyzed to identify the causative pathogens.\n Both medications were equally well tolerated by the patients. The treatment was successful for all patients of the NCT group, whereas in one patient from the reference group, the infection did not disappear. The inflammation score improved more rapidly in the NCT group, which resulted in an earlier termination of the therapy. This difference became highly significant on days 4 to 7 (P <.01 each). Time needed for disappearance of inflammation (score 0) was 5.6 +/- 1.6 (mean +/- SD, range 3-9) days in the NCT group and 7.4 +/- 1.6 (range 4-10) days in the Otosporin group (P <.001). As expected, microbiologic cultures from ear swabs revealed Pseudomonas aeruginosa (58%) followed by Staphylococcus aureus (18%) as the main causative pathogens.\n NCT appears to be well tolerated and more effective than the therapy using antibiotic component drops. Because of its endogenous nature and its higher efficacy, NCT appears to be a good choice for topical treatment of acute otitis externa."
] |
Topical quinolone antibiotics can clear aural discharge better than no drug treatment or topical antiseptics; non-quinolone antibiotic effects (without steroids) versus no drug or antiseptics are less clear. Studies were also inconclusive regarding any differences between quinolone and non-quinolone antibiotics, although indirect comparisons suggest a benefit of topical quinolones cannot be ruled out. Further trials should clarify non-quinolone antibiotic effects, assess longer-term outcomes (for resolution, healing, hearing, or complications) and include further safety assessments, particularly to clarify the risks of ototoxicity and whether quinolones may result in fewer adverse events than other topical treatments.
|
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.