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CD004003	[ "15064026", "16905024", "10227221", "9291741", "7823670" ]	[ "Role of flies and provision of latrines in trachoma control: cluster-randomised controlled trial.", "Intensive insecticide spraying for fly control after mass antibiotic treatment for trachoma in a hyperendemic setting: a randomised trial.", "Effect of fly control on trachoma and diarrhoea.", "Health education and antibiotic therapy in trachoma control.", "Impact of face-washing on trachoma in Kongwa, Tanzania." ]	[ "Eye-seeking flies have received much attention as possible trachoma vectors, but this remains unproved. We aimed to assess the role of eye-seeking flies as vectors of trachoma and to test provision of simple pit latrines, without additional health education, as a sustainable method of fly control.\n In a community-based, cluster-randomised controlled trial, we recruited seven sets of three village clusters and randomly assigned them to either an intervention group that received regular insecticide spraying or provision of pit latrines (without additional health education) to each household, or to a control group with no intervention. Our primary outcomes were fly-eye contact and prevalence of active trachoma. Frequency of child fly-eye contact was monitored fortnightly. Whole communities were screened for clinical signs of trachoma at baseline and after 6 months. Analysis was per protocol.\n Of 7080 people recruited, 6087 (86%) were screened at follow-up. Baseline community prevalence of active trachoma was 6%. The number of Musca sorbens flies caught from children's eyes was reduced by 88% (95% CI 64-100; p<0.0001) by insecticide spraying and by 30% (7-52; p=0.04) by latrine provision by comparison with controls. Analysis of age-standardised trachoma prevalence rates at the cluster level (n=14) showed that spraying was associated with a mean reduction in trachoma prevalence of 56% (19-93; p=0.01) and 30% with latrines (-81 to 22; p=0.210) by comparison with the mean rate change in the controls.\n Fly control with insecticide is effective at reducing the number of flies caught from children's eyes and is associated with substantially lower trachoma prevalence compared with controls. Such a finding is consistent with flies being important vectors of trachoma. Since latrine provision without health education was associated with a significant reduction in fly-eye contact by M sorbens, studies of their effect when combined with other trachoma control measures are warranted.", "There are no data on the cumulative effect of fly control and antibiotic distribution on trachoma in hyperendemic communities. We sought to determine whether insecticide spray intervention after mass antibiotic treatment could reduce trachoma and ocular infection with Chlamydia trachomatis in hyperendemic neighbourhoods in Tanzania.\n We did a single-blind, randomised clinical trial in 16 neighbourhoods (balozi) in Kongwa, Tanzania. All children aged 1-7 years were enrolled, with 119 children in the eight balozi of the intervention group and 183 in the eight control balozi. Children were examined at baseline, 6 months, and 1 year for clinical trachoma and ocular C trachomatis infection. One dose of azithromycin was offered to all residents of both intervention and control balozi after the baseline survey. Households (and surrounding areas) in the intervention group were then sprayed with insecticide throughout the ensuing year and monitored for reductions in fly counts. This study is registered at ClinicalTrials.gov, number NCT00347763.\n The intervention balozi had significantly lower fly counts than controls at all monitored weeks (p<0.05), apart from weeks 7-9. The trachoma rate did not differ significantly in the intervention and control balozi at 6 months post-treatment (20%vs 33%, p=0.07), nor did it at 1 year (43%vs 44%, p=0.90). Infection with C trachomatis did not differ between groups at 6 months post-treatment (9%vs 7%, p=0.45).\n Intensive insecticide spraying reduced flies in the environment, but our results suggest that fly reduction after mass antibiotic treatment has no added benefit on reduction of trachoma.", "Domestic flies are accepted vectors of diarrhoea, but their role in trachoma transmission has never been quantified and no study has shown that fly control decreases the prevalence of trachoma. We assessed the effect of fly control on public health in a pilot study in Gambian villages.\n We studied two pairs of villages--one pair in the 1997 wet season, and one pair in the 1998 dry season. For each pair, deltamethrin was sprayed for 3 months to control flies in one village whilst the other was used as a control. Fly populations were monitored with traps. We surveyed trachoma at baseline and at 3 months, and collected daily data on diarrhoea in children aged between 3 months and 5 years.\n Fly control decreased numbers of muscid flies by around 75% in the intervention villages compared with controls. Trachoma prevalence was similar at baseline (wet season, prevalence in intervention village 8.8% vs control 12.2%; dry season, 18.0% vs 16.0%), but after 3 months of fly control there were 75% fewer new cases of trachoma in the intervention villages (wet season 3.7% vs 13.7%; dry season 10.0% vs 18.9%; rate ratio and relative risk of pooled data 0.25 [adjusted 95% CI 0.09-0.64], p=0.003). There was 22% less childhood diarrhoea in the wet season (14% vs 19%, period prevalence ratio 0.78 [0.64-0.95], p=0.01), and 26% less diarrhoea in the dry season (6% vs 8%; 0.74 [0.34-1.59], p=0.60) compared with controls.\n Muscid flies are important vectors of trachoma and childhood diarrhoea in The Gambia. Deltamethrin spray is effective for fly control and may be useful for reducing trachoma and diarrhoea in some situations, but further research on sustainable fly-control methods is needed.", "The objective of this study was to confirm whether the combination of a health education programme with a mass treatment campaign was able to improve the effectiveness of trachoma control. An open controlled clinical trial with a 2 x 2 factorial design was carried out. Four villages, matched for size and epidemiological, economic and social conditions, were included in the study. The first village received mass treatment with 1% oxytetracycline eye drops combined with a specific health education programme. The second village received only a health education programme. The third village received only mass treatment and the fourth village did not receive any intervention during the study (control village). 1810 subjects were enrolled of whom 76% were successfully followed for 6 months. The incidence of new cases ranged between 1.6% and 14.2%. In this study the combination of a health education programme with mass treatment failed to increase the cure rate. There was even a negative interaction (P = 0.03). The best results were obtained in the village where antibiotic treatment was used alone, both in terms of cure rate (82%) and reduction of C trachomatis transmission. These results suggest that the addition of a health education programme does not systematically improve the performances of a mass treatment campaign. The efficacy of this combination depends essentially on the capacity of the community to modify its hygiene behaviour.", "Observational studies have suggested that the prevalence of trachoma is lower in children with clean faces than in those with ocular or nasal discharge or flies on the face. We carried out a community-based randomised trial in three pairs of villages to assess the impact on trachoma of a face-washing intervention programme following a mass topical antibiotic treatment campaign. Six villages in Kongwa, Tanzania, were randomly assigned mass treatment plus the face-washing programme or treatment only. 1417 children aged 1-7 years in these villages were randomly selected and followed up for trachoma status and observations of facial cleanliness at baseline and 2, 6, and 12 months. At 12 months, children in the intervention villages were 60% more likely to have had clean faces at two or more follow-up visits than children in the control villages. The odds of having severe trachoma in the intervention villages were 0.62 (95% Cl 0.40-0.97) compared with control villages. A clean face at two or more follow-up visits was protective for any trachoma (odds ratio 0.58 [0.47-0.72]) and severe trachoma (0.35 [0.21-0.59]). This community-based participatory approach to face-washing intervention had variable penetration rates in the villages and was labour intensive. However, we found that, combined with topical treatment, community-based strategies for improving hygiene in children in trachoma-endemic villages can reduce the prevalence of trachoma." ]	There is some evidence from two trials that insecticides are effective in reducing trachoma, however, this effect was not demonstrated in another trial that used insecticides. Two trials on latrine provision as a fly control measure have not demonstrated significant trachoma reduction. Health education had shown significant reduction of trachoma in one study but another study did not demonstrate similar findings. Generally there is a dearth of data to determine the effectiveness of all aspects of environmental sanitation in the control of trachoma.
CD007897	[ "10842461", "11128878", "15068207", "17035145", "17699530", "22054336", "3654234" ]	[ "Improved health after intervention in a school with moisture problems.", "Respiratory morbidity among children following renovation of a water-damaged school.", "The remediation of mold damaged school--a three-year follow-up study on teachers' health.", "Reduction in asthma morbidity in children as a result of home remediation aimed at moisture sources.", "The Watcombe Housing Study: the short term effect of improving housing conditions on the health of residents.", "Enhancing ventilation in homes of children with asthma: pragmatic randomised controlled trial.", "A school health education program for children with asthma aged 8-11 years." ]	[ "In a school with floor moisture problems, the personnel had complaints consistent with the sick-building syndrome (SBS). Interventive measures including the laying of a ventilated floor were undertaken to eliminate the emissions. To examine if the intervention resulted in positive health effects, 34 personnel and 336 pupils were interviewed just before the intervention and also 7 months after. Also were interviewed 21 personnel and 224 pupils at an adjacent school serving as a control. Compared with the control school, the problem school showed more complaints, more general symptoms and more symptoms from the eyes, airways and skin, both among the personnel and the pupils. In the post-intervention examinations, the excess of symptoms among the personnel had almost disappeared. Among the pupils, the frequency of eye irritation was reduced but a general improvement of the other symptoms was not as obvious. However, after adjustment for a recent common cold, atopy and stress among the pupils, only one symptom (\"stuffy nose\") remained significantly elevated. In conclusion, the intervention was followed by positive health effects, supporting the hypothesis that emissions from building material had contributed to the excess of symptoms. A recent common cold was highly related to the symptoms and should be considered in future SBS studies.", "The authors sought to determine whether exposure to molds, resulting from moisture damage in a school, was associated with increased respiratory symptoms and morbidity among schoolchildren and whether the renovation of this building resulted in a decrease in prevalence of respiratory symptoms and morbidity. The study was a follow-up (1-y interval) of children between the ages of 7 and 12 y from two elementary schools in a Finnish suburb. In addition to a questionnaire completed by the parents, the authors assessed the respiratory health of children by examining the health records of a local health center. In the cross-sectional study, the prevalence of symptoms and infections were higher in the exposed group, as were visits to a physician and use of antibiotics. The school was renovated, after which all prevalence decreased and no significant differences remained, except for visits to a physician (according to questionnaire responses). Therefore, moisture damage and exposure to molds increased the indoor air problems of schools and affected the respiratory health of children.", "The health effects in teachers of a mold-damaged school before and during an extensive remediation process were assessed. Health data were collected with self-administered questionnaires from teachers (n=31) working in a moisture and mold damaged school and from the reference group of teachers (n=13) working in a non-damaged school. The questionnaire study was repeated three times. Spirometry was measured in 33 individuals in the spring 1997 and repeated in the spring 1999 and 2000. In the damaged school, a cluster of eight asthma cases was identified, the prevalence of asthma being 26%. Before the remediation, the number of sinusitis episodes was higher (p=0.040) and the mean duration of sick leaves longer (p=0.015) among the study group than in the reference group. A higher prevalence of hoarseness and perceived poor quality of indoor air were reported. During the follow-up, no new asthma cases appeared. After the remediation, bronchitis, conjunctivitis, symptoms of allergic rhinitis and the sum of respiratory infection episodes decreased significantly. Some of the asthmatics had low values in the spirometry but no changes in the lung function were observed at the group level. The remediation of the mold damage had beneficial effects on teachers' health.", "Home dampness and the presence of mold and allergens have been associated with asthma morbidity. We examined changes in asthma morbidity in children as a result of home remediation aimed at moisture sources.\n In this prospective, randomized controlled trial, symptomatic, asthmatic children (n = 62), 2-17 years of age, living in a home with indoor mold, received an asthma intervention including an action plan, education, and individualized problem solving. The remediation group also received household repairs, including reduction of water infiltration, removal of water-damaged building materials, and heating/ventilation/air-conditioning alterations. The control group received only home cleaning information. We measured children's total and allergen-specific serum immuno-globulin E, peripheral blood eosinophil counts, and urinary cotinine. Environmental dust samples were analyzed for dust mite, cockroach, rodent urinary protein, endotoxin, and fungi. The follow-up period was 1 year.\n Children in both groups showed improvement in asthma symptomatic days during the preremediation portion of the study. The remediation group had a significant decrease in symptom days (p = 0.003, as randomized; p = 0.004, intent to treat) after remodeling, whereas these parameters in the control group did not significantly change. In the postremediation period, the remediation group had a lower rate of exacerbations compared with control asthmatics (as treated: 1 of 29 vs. 11 of 33, respectively, p = 0. 003; intent to treat: 28.1% and 10.0%, respectively, p = 0.11).\n Construction remediation aimed at the root cause of moisture sources and combined with a medical/behavioral intervention significantly reduces symptom days and health care use for asthmatic children who live in homes with a documented mold problem.", "To assess the short term health effects of improving housing.\n Randomised to waiting list.\n 119 council owned houses in south Devon, UK.\n About 480 residents of these houses.\n Upgrading houses (including central heating, ventilation, rewiring, insulation, and re-roofing) in two phases a year apart.\n All residents completed an annual health questionnaire: SF36 and GHQ12 (adults). Residents reporting respiratory illness or arthritis were interviewed using condition-specific questionnaires, the former also completing peak flow and symptom diaries (children) or spirometry (adults). Data on health service use and time lost from school were collected.\n Interventions improved energy efficiency. For those living in intervention houses, non-asthma-related chest problems (Mann-Whitney test, p = 0.005) and the combined asthma symptom score for adults (Mann-Whitney test, z = 2.7, p = 0.007) diminished significantly compared with control houses. No difference between intervention and control houses was seen for SF36 or GHQ12.\n Rigorous study designs for the evaluation of complex public health and community based interventions are possible. Quantitatively measured health benefits are small, but as health benefits were measured over a short time scale, there may have been insufficient time for measurable improvements in general and disease-specific health to become apparent.", "Few robust studies have tested whether enhancing housing also improves health.\n To evaluate the effectiveness of installing ventilation systems, and central heating where necessary, in the homes of children with moderate or severe asthma.\n Pragmatic randomised controlled trial (RCT) in homes within Wrexham County Borough, Wales, UK.\n A pragmatic RCT was carried out, of a tailored package of housing improvements providing adequate ventilation and temperature, following inspection by a housing officer. One hundred and ninety-two children with asthma aged 5 to 14 years, identified from general practice registers, were randomised to receive this package, either immediately or a year after recruitment. At baseline, and after 4 and 12 months, parents reported their child's asthma-specific and generic quality of life, and days off school.\n The package improved parent-reported asthma-specific quality of life significantly at both 4 and 12 months. At 12 months, this showed an adjusted mean difference between groups of 7.1 points (95% confidence interval [CI] = 2.8 to 11.4, P= 0.001): a moderate standardised effect size of 0.42. The generic quality-of-life scale showed reported physical problems were significantly reduced at 4 months, but not quite at 12 months, when the mean difference was 4.5 (95% CI = -0.2 to 9.1, P= 0.061). The improvement in psychosocial quality of life at 12 months was not significant, with a mean difference of 2.2 (95% CI = -1.9 to 6.4, P= 0.292). Parent-reported school attendance improved, but not significantly.\n This novel and pragmatic trial, with integrated economic evaluation, found that tailored improvement of the housing of children with moderate to severe asthma significantly increases parent-reported asthma-related quality of life and reduces physical problems. Collaborative housing initiatives have potential to improve health.", "It was hypothesized that a health education program for children with asthma aged 8-11 years that was delivered in elementary schools, would increase children's asthma management skills, self-efficacy and influence on parents' management decisions; reduce school absences and improve school performance. The study population consisted of 239 low-income, predominantly Hispanic and black children from 12 elementary schools (six experimental and six control) in New York City. Parents did not attend educational sessions but received written materials. The program emphasized the child's responsibility for recognizing symptoms and taking appropriate management steps. Follow-up data obtained one year after the program showed that compared to controls experimental group children had higher scores on an index of asthma management (p less than 0.05), greater self-efficacy with respect to asthma management skills (p less than 0.05), more influence on parents' asthma management decisions (p less than 0.05), better grades in school (p = 0.05), and fewer episodes of asthma (p less than 0.01) of shorter average duration (p less than 0.01). No differences were observed for changes in number of school absences. These findings show that asthma health education designed for delivery to children can significantly increase management skills, reduce symptoms of asthma, and improve school performance." ]	We found moderate to very low-quality evidence that repairing mould-damaged houses and offices decreases asthma-related symptoms and respiratory infections compared to no intervention in adults. There is very low-quality evidence that although repairing schools did not significantly change respiratory symptoms in staff or children, pupils' visits to physicians due to a common cold were less frequent after remediation of the school. Better research, preferably with a cRCT design and with more validated outcome measures, is needed.
CD004968	[ "1634627" ]	[ "A randomized trial of occlusal adjustment in the treatment of periodontitis patients." ]	[ "The purpose of the randomized clinical trial was to test; (1) the influence of occlusal adjustment (OA) in association with periodontal therapy on attachment levels, pocket depth, and tooth mobility, (2) whether OA was of greater significance in non-surgically treated periodontal defects, and (3) whether initial tooth mobility or disease severity had an affect on post-treatment attachment levels following OA. After hygienic-phase therapy, 50 patients received OA/No OA according to random assignment; 22 patients received an OA and 28 were not adjusted. 2 months after OA, either modified Widman flap surgery or scaling and root planing by a periodontist were done according to random assignment within each patient in a split-mouth design. Following active treatment patients were maintained with prophylaxis done every 3 months and scored annually. For the analysis of this two-year data, a repeated measures analysis of variance was performed using attachment level change and pocket depths as outcome indicators. There was significantly greater gain of clinical periodontal attachment in patients who received an OA compared to those who did not. Both the surgically and non-surgically treated sides of the mouth responded similarly to OA. There was no affect of OA on the response in pocket depth, nor did initial tooth mobility or initial periodontal disease severity influence the response to OA." ]	There is only one randomised trial that has addressed this question. The data from this study are inconclusive. We therefore conclude there is no evidence for or against the use of occlusal interventions in clinical practice. This question can only be addressed by adequately powered bias-protected randomised controlled trials.
CD009508	[ "21820536", "12576255", "7345161", "21425721", "18094892", "17245777", "9849757", "20179901", "17763226", "19690792", "19281321", "19649552", "9136139", "15339760", "15791633" ]	[ "Is pelvic floor muscle training effective when taught in a general fitness class in pregnancy? A randomised controlled trial.", "Pelvic floor muscle training during pregnancy to prevent urinary incontinence: a single-blind randomized controlled trial.", "Do pelvic floor exercises really improve orgasmic potential?", "Effectiveness of pelvic floor muscle training in incontinent women at Maharaj Nakorn Chiang Mai Hospital: a randomized controlled trial.", "Impact of supervised physiotherapeutic pelvic floor exercises for treating female stress urinary incontinence.", "Short-term efficacy of group pelvic floor training under intensive supervision versus unsupervised home training for female stress urinary incontinence: a randomized pilot study.", "A randomized controlled trial of pelvic floor muscle exercises to treat postnatal urinary incontinence.", "Intensive supervised versus unsupervised pelvic floor muscle training for the treatment of stress urinary incontinence: a randomized comparative trial.", "Pelvic floor muscle training before transurethral resection of the prostate: a randomized, controlled, blinded study.", "Pelvic floor muscle training in female stress urinary incontinence: comparison between group training and individual treatment using PERFECT assessment scheme.", "Randomized trial of circular muscle versus pelvic floor training for stress urinary incontinence in women.", "Effect of pelvic floor muscle exercises in the treatment of urinary incontinence during pregnancy and the postpartum period.", "Cues to action: pelvic floor muscle exercise compliance in women with stress urinary incontinence.", "Physiotherapy for persistent postnatal stress urinary incontinence: a randomized controlled trial.", "Pelvic floor muscle training is effective in women with urinary incontinence after stroke: a randomised, controlled and blinded study." ]	[ "Pelvic floor muscle training (PFMT) following vaginal assessment of correct contraction can prevent and treat urinary incontinence in the peripartum period. The aim of this study was to evaluate the effectiveness of PFMT instructed in a general fitness class for pregnant women.\n Single-blind randomised controlled trial.\n University-conducted primary care study.\n One hundred and five sedentary primiparous women randomised to a general fitness class including PFMT (n=52) or a control group (n=53). Ten and 11 women were lost to follow-up in the exercise and control groups, respectively.\n Twelve weeks of training comprising twice-weekly 1-hour fitness classes including three sets of eight to 12 maximal pelvic floor muscle contractions. The control group received usual care.\n Number of women reporting urinary, flatus or anal incontinence.\n No significant differences were found in the number of women reporting urinary, flatus or anal incontinence between the exercise group and the control group during pregnancy or at 6 weeks post partum.\n No effect of PFMT was found when the exercises were taught in a general fitness class for pregnant women without individual instruction of correct PFM contraction. Low adherence and the small sample size may have contributed to the negative results. Further studies are warranted to assess the effect of population-based PFMT in the prevention of urinary and fecal incontinence.\n Copyright © 2010 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.", "Urinary incontinence is a chronic health complaint that severely reduces quality of life. Pregnancy and vaginal delivery are main risk factors in the development of urinary incontinence. The aim of this study was to assess whether intensive pelvic floor muscle training during pregnancy could prevent urinary incontinence.\n We conducted a single-blind randomized controlled trial at Trondheim University Hospital and three outpatient physiotherapy clinics in a primary care setting. Three hundred one healthy nulliparous women were randomly allocated to a training (n = 148) or a control group (n = 153). The training group attended a 12-week intensive pelvic floor muscle training program during pregnancy, supervised by physiotherapists. The control group received the customary information. The primary outcome measure was self-reported symptoms of urinary incontinence. The secondary outcome measure was pelvic floor muscle strength.\n At follow-up, significantly fewer women in the training group reported urinary incontinence: 48 of 148 (32%) versus 74 of 153 (48%) at 36 weeks' pregnancy (P =.007) and 29 of 148 (20%) versus 49 of 153 (32%) 3 months after delivery (P =.018). According to numbers needed to treat, intensive pelvic floor muscle training during pregnancy prevented urinary incontinence in about one in six women during pregnancy and one in eight women after delivery. Pelvic floor muscle strength was significantly higher in the training group at 36 weeks' pregnancy (P =.008) and 3 months after delivery (P =.048).\n Intensive pelvic floor muscle training during pregnancy prevents urinary incontinence during pregnancy and after delivery. Pelvic floor muscle strength improved significantly after intensive pelvic floor muscle training.", "Women with orgasmic difficulties are commonly taught pubococcygeal (PC) muscle exercises which, practiced regularly, are said to have both specific and nonspecific beneficial effects on sexual enjoyment. The hypothesis tested was that women practicing these exercises over a 12-week period, would be more likely to become orgasmic than women practicing relaxation exercises, or than women in an attention-control group. Forty-six women were allocated to one of three groups, PC exercise, relaxation or control. PC muscle tone was measured and questionnaires about sexual response were completed over a 12-week period with a 6-month follow-up assessment. Results indicated that there was no difference in orgasmic outcome for the three groups during the experimental period. This was taken to imply that PC exercises are not of specific value for women with normal muscle tone. It remains possible that women with poor muscle tone are helped by the exercises and further research is considered necessary in this area.", "To compare the effects ofthree different pelvic floor muscle training (PFMT) in stress urinary incontinence (SUI) women.\n Sixty-eight eligible SUI women who could perform pelvic floor muscle contraction correctly were randomly allocated to the three diferent PFMT protocols, exercise every day (GJ), exercise three days per week (G2), and exercise plus abdominal training three days per week (G3). The primary outcome was pad test. The secondary outcomes were pelvic floor muscle strength, and treatment satisfaction. The outcomes were evaluated before and after a 12-week of exercise.\n The weights ofpad were decreased by 2.6 +/- 0.8, 2.3 +/- 1.3, and 3.1 +/- 1.3 grams for group 1, 2, and 3, respectively. There was no statistical significant difference among the three groups. The pelvic floor muscle strength was increased by 18.4 +/- 2.7, 13.9 +/- 2.9, and 17.3 +/- 3.0 cmH2O for group 1, 2, and 3, respectively, with statistical significant difference among groups (p < 0.00). The increased muscle strength in group 2 was significant less than the other two groups (p < 0.00). Treatment Satisfaction showed the leakage was improved with non-significant difference between groups (p > 0.05). No complications were seen in any of the groups.\n Even though the results showed non-significant decrease in pad's weight among the three training groups, the pelvic floor muscle strength were increased in all groups.", "Urinary incontinence is a public health problem that affects more than 200 million people worldwide. Stress incontinence is the most prevalent type. Pelvic floor muscle exercises have been used for treating it, although there is no consensus regarding their application. The aim of this study was to compare the results from treating female stress urinary incontinence with pelvic floor muscle exercises with or without physiotherapist supervision.\n This was a randomized, prospective, controlled trial in the Urogynecology and Vaginal Surgery Sector, Universidade Federal de São Paulo.\n Forty-four women were randomized to be treated for stress urinary incontinence with pelvic floor exercises for three consecutive months, into two groups: one with and the other without physiotherapist supervision. They were evaluated before and after treatment using a quality-of-life questionnaire, pad test, micturition diary and subjective evaluation. Descriptive analysis was used to evaluate the population. The homogeneity of the two groups was evaluated using the Kruskal-Wallis and Chi-squared tests. The success of the two groups after treatment was evaluated using the Wilcoxon test.\n The supervised group showed statistically greater improvement in the pad test, micturition diary and quality of life than did the control group. In the subjective evaluation, only 23.8% of the control group patients were satised with their treatment. In the supervised group, 66.8% of patients did not want any other treatment.\n Supervised pelvic floor muscle exercises presented better results in objective and subjective evaluations than did unsupervised exercises.", "Current management guidelines propose pelvic floor muscle training (PFMT) as first line treatment for female stress urinary incontinence (SUI). The aim of this study is to compare the efficacy of group PFMT under intensive supervision to that of individual home therapy in women with SUI.\n Thirty women with clinical and urodynamic diagnosis of SUI were randomized in two equal-number groups. Following a common demonstration course, Group A women received a detailed schedule for home training, while Group B in addition attended a weekly hospital group visit. At 12 weeks both groups were assessed for changes in subjective and objective outcomes.\n Twenty-two women, (10 Group A, 12 Group B) with a mean age of 47.3 years completed the study. Although significant (P<0.05) improvements were noted in both groups in quality of life scores, number of incontinence episodes/week, 24-hr frequency, and endurance, repetitions and fast contractions upon vaginal assessment of the PFMs, comparative analysis at the end of the study demonstrated significantly better results for women in Group B, who also improved in daily pad usage, underwear wetting, modified Oxford grading of the PFMs and hold with cough. Consequently, significantly more women in Group B reported improvement in their continence (100% vs. 20% in Group A).\n Group PFMT under intensive supervision produced significantly better improvements in primary and secondary outcomes in the short-term compared to individual, unsupervised home application of PFMT.\n Copyright (c) 2007 Wiley-Liss, Inc.", "A randomized controlled trial was carried out to evaluate the extent to which a program of reinforced pelvic floor muscle exercises (PFME) reduces urinary incontinence 1 year after delivery. Two hundred and thirty women who were incontinent 3 months postpartum were randomized to either a control group doing standard postnatal pelvic floor muscle exercises (n = 117) or to an intervention group (n = 113) who saw a physiotherapist for instruction at approximately 3, 4, 6 and 9 months postpartum. Results collected 12 months after delivery included prevalence and frequency of incontinence and PFME, sexual satisfaction, perineometry measurements and pad tests. Twenty-six (22%) of the control group and 59 (52%) of the intervention group withdrew before the final assessment. The prevalence of incontinence was significantly less in the intervention group than in the control group (50% versus 76%, P=0.0003), and this group also did significantly more PFME. There were no significant differences between the groups as regards sexual satisfaction, perineometry measurements or pad test results.", "Pelvic floor muscle training (PFMT) is considered to be the first-line treatment for female stress urinary incontinence (SUI). There are few studies that have tested the efficacy of unsupervised PFMT. The aim of this study was to compare the effectiveness of intensive supervised PFMT to unsupervised PFMT in the treatment of female SUI.\n Sixty-two women with SUI were randomized to either supervised or unsupervised PFMT after undergoing supervised training sessions. They were evaluated before and after the treatment with the Oxford grading system, pad test, quality of life questionnaire, subjective evaluation, and exercise compliance.\n After treatment, there were no differences between the two groups regarding PFM strength (p = 0.20), International Consultation on Incontinence Questionnaire-Short Form score (p = 0.76), pad test (p = 0.78), weekly exercise compliance (p = 0.079), and subjective evaluation of urinary loss (p = 0.145).\n Both intensive supervised PFMT and unsupervised PFMT are effective to treat female SUI if training session is provided.", "OBJECTIVE To evaluate the effect of preoperative pelvic floor muscle training (PFMT) in men scheduled for transurethral resection of the prostate (TURP) in a randomized, single-blind study.\n Fifty-eight men with benign prostatic obstruction were included, and 49 completed the study (training group, n=26; control group, n=23). The preoperative training included a 1-h individual lesson, three 1-h group lessons and a home training programme. Postoperatively and before discharge from hospital both groups received verbal instructions regarding PFMT. Pelvic floor muscle function was assessed by anal examination before and 4 weeks after surgery by one physiotherapist who was blinded to the randomization. The primary outcome parameter was the total score on the Danish Prostatic Symptom Score questionnaire. Secondary outcome measures were other subjective and objective voiding and incontinence parameters and four tests of the pelvic floor muscle: function; strength; static endurance; and dynamic endurance.\n Baseline characteristics were similar in the two groups. Improved static endurance occurred in the training group but not in the control group (p=0.004). Regarding dynamic endurance, a difference in favour of training developed between the groups (p=0.049). Many men produced results that were outside the test scales. At follow-up at 2 and 4 weeks and 3 months there were no differences between the groups in any of the lower urinary tract parameters.\n Preoperative PFMT produced a significant improvement in pelvic floor muscle endurance after TURP, but clinically relevant storage or voiding improvements did not occur. Pelvic floor muscle assessment tests need to be sex-specific.", "Pelvic floor muscle training (PFMT) is a treatment for stress urinary incontinence (SUI) that can be done individually or in a group. The aim of this study was to compare these two types of treatment.\n Sixty women 30 to 75 years old with SUI were randomly assigned to participate in the two groups. They were evaluated before and after the treatment with the Oxford grading system, pad test, voiding diary, and the King's Health Questionnaire.\n Both groups experienced significant reductions in urinary leakage as measured by the pad test and bladder diary. A negative pad test was observed in about 50% of patients in both groups. There were statistically significant improvements in both muscle strength and quality of life. When the groups were compared, there were no differences in the results between them.\n Individual treatment and group PFMT appear to be equally effective for improving SUI.", "Conservative management, such as pelvic floor muscle training (PMFT), is commonly recommended as first-line therapy for women with stress urinary incontinence (SUI).\n We randomly assigned 245 women with SUI to 12 weeks of circular muscle exercises (Paula method) or PMFT in order to assess whether these approaches are equivalent. End points after 12 weeks included urinary leak as measured by a 1-hour pad test, subjective assessment of incontinence, and quality of life (QOL). Cure was defined as urinary leakage of <1 g.\n The mean decrease in urinary leakage was 7.9 g (SD 12.1) among women in the Paula group and 8.9 g (SD 18.2) in the PFMT group (90% confidence interval [CI] of between-group difference was -4.68 g to 3.0 g). This did not meet the prespecified criterion for equivalence. There were 15.2% (p = 0.04) more cures in those randomized to the Paula method. Improvement in subjective urinary complaints and QOL was observed in both groups. The study was limited by a dropout rate of 26.6%.\n Both methods are efficacious in women with SUI. The results suggest superiority of the Paula method in terms of cure rate.", "The aim of this study was to determine the effectiveness of pelvic floor muscle exercises on urinary incontinence during pregnancy and the postpartum period.\n The study was carried out on 80 pregnant women (study group, 40 subjects; control group, 40 subjects).The study group was trained by the researcher on how to do the pelvic floor muscle exercises. Both groups were evaluated for pelvic floor muscle strength and urinary complaints in their 36th to 38th week of pregnancy and postpartum sixth to eighth week.\n The study group had a significant decrease in urinary incontinence episodes during pregnancy and in the postpartum period, and their pelvic floor muscle strength increased to a larger extent. Control group had an increase in the postpartum muscle strength and decrease in the incontinence episodes in the postpartum period.\n Pelvic floor muscle exercises are quite effective in the augmentation of the pelvic floor muscle strength and consequently in the treatment of urinary incontinence.", "Pelvic floor muscle exercises are recommended as an initial treatment to women with stress urinary incontinence. This treatment is often unsuccessful because of patient noncompliance. A post-test, experimental control group design was used to examine Pender's (1992) concept of an external cue to action, an audiocassette tape, to enhance patient compliance to pelvic floor exercises. Eighty-six women with urodynamically evaluated stress urinary incontinence participated through a Pelvic Floor Exercise Unit at a large teaching hospital. Patients received biofeedback training and written information to reinforce pelvic floor muscle exercises during a 45-min appointment with a nurse. Patients were instructed to perform the exercises for 10 min twice daily. Forty-three women randomly assigned to an experimental group received an audiocassette tape. Four to 6 weeks later all patients completed a researcher-developed questionnaire that was validity and reliability tested assessing pelvic floor exercise compliance. The 43 patients (100%) who received the audiocassette tape reported compliance with \"routine\" exercises. Twenty-two of 34 patients (65%) who did not receive the tape were compliant (P = 0.0003). Thirty-four of 41 patients (83%) who received the tape reported exercise compliance twice a day, while 4 of 34 patients (12%) in the control group were similarly compliant (P = 0.0000). The findings suggest adding an audiocassette tape to a pelvic floor exercise program enhances patient compliance for incontinent women compared to verbal and written instruction combined with biofeedback.", "The aim of this study was to compare the effectiveness of multimodal supervised physiotherapy programs with the absence of treatment among women with persistent postnatal stress urinary incontinence.\n This was a single-blind randomized controlled trial. Sixty-four women with stress urinary incontinence were randomly assigned to 8 weeks of either multimodal pelvic floor rehabilitation (n = 21), multimodal pelvic floor rehabilitation with abdominal muscle training (n = 23), or control non-pelvic floor rehabilitation (n = 20). The primary outcome measure consisted of a modified 20-minute pad test. The secondary outcome measures included a Visual Analog Scale describing the perceived burden of incontinence, the Urogenital Distress Inventory, the Incontinence Impact Questionnaire, and pelvic floor muscle function measurements.\n Two patients dropped out, leaving 62 for analysis. At follow-up, more than 70% of the women in the treatment groups (14/20 in the pelvic floor and 17/23 in the pelvic floor plus abdominal group) were continent on pad testing compared with 0% of women in the control group. Scores on the pad test, Visual Analog Scale, Urogenital Distress Inventory, and Incontinence Impact Questionnaire improved significantly in both treatment groups (all P <.002), whereas no changes were observed in the control group. Pelvic floor muscle function, however, did not improve significantly in either active group.\n Multimodal supervised pelvic floor physiotherapy is an effective treatment for persistent postnatal stress urinary incontinence.", "The aim of this study was to evaluate the effect of Pelvic Floor Muscle Training (PFMT) in women with urinary incontinence (UI) after ischemic stroke.\n Three hundred and thirty-nine medical records of stroke patients were searched. Twenty-six subjects were randomised to a Treatment Group (14 subjects) or a Control Group (12 subjects) in a single blinded, randomised study. The intervention included 12 weeks of standardised PFMT. The outcome measures were: (1) diary recording the frequency of voiding, the number of incontinence episodes and used pads; (2) 24-hr home pad test; and (3) vaginal palpation of pelvic floor muscle evaluating function, strength, static and dynamic endurance.\n Twenty-four subjects with urge, stress and mixed stress/urge incontinence, completed the study, 12 in each group. A significant improvement in frequency of voiding in daytime (Treatment Group/Control Group: 7/8 at pre-test, 6/9 at post-test (median values), P=0.018), 24-hr pad test (Treatment Group/Control Group: 8/12 to 2/8 g P=0.013) and dynamic endurance of pelvic floor muscle (Treatment Group/Control Group: 11/20 to 20/8 contractions of Pelvic Floor Muscle, P=0.028) was demonstrated in the Treatment Group compared to the Control Group. A significant improvement in frequency of voiding in daytime (decreased from seven to six, P=0.036), pelvic floor muscle function (P=0.034), strength (P=0.046), static endurance increased from 9 to 30 sec (P=0.028) and dynamic endurance increased from 11 to 20 contractions (P=0.020) was also demonstrated within the Treatment Group, but not in the Control Group.\n PFMT had a significant effect in women with UI after stroke measured by diaries, pad tests and vaginal palpation.\n Copyright (c) 2005 Wiley-Liss, Inc." ]	This review found that the existing evidence was insufficient to make any strong recommendations about the best approach to pelvic floor muscle training. We suggest that women are offered reasonably frequent appointments during the training period, because the few data consistently showed that women receiving regular (e.g. weekly) supervision were more likely to report improvement than women doing pelvic floor muscle training with little or no supervision.
CD007748	[ "6708033" ]	[ "Comparison of magnesium sulfate, terbutaline and a placebo for inhibition of preterm labor. A randomized study." ]	[ "Magnesium sulfate has been recommended as a safe and effective agent for inhibiting preterm labor. Its reported adequacy as a tocolytic agent, however, has not been substantiated by randomized, controlled trials. To assess the efficacy of magnesium sulfate, we initiated a prospective, randomized study comparing the capabilities of magnesium sulfate, terbutaline and a placebo (5% dextrose in lactated Ringer's solution) for labor inhibition. The study population consisted of 54 patients between 26 and 34 weeks of gestation and in preterm labor. The diagnosis of labor was made if, following hydration, persistent uterine contractions occurred at a frequency of at least three in a ten-minute period and cervical examination suggested active labor. Success was defined as postponement of delivery for at least 48 hours after initiation of therapy. Despite a trend toward increased efficacy in the terbutaline group there were no significant differences between the three treatment groups with regard to capability of delaying delivery at least 48 hours. Also, there were no significant differences between the groups with regard to gestational age at delivery, birth weight and neonatal survival. The fact that delivery occurred in less than 48 hours of approximately one-half the patients under the best of circumstances emphasizes the need for more effective techniques for the inhibition of preterm labor and the need for a better understanding of the mechanisms involved in the initiation of preterm labor." ]	There was very little evidence about using COX inhibitors for preventing preterm labour. There are inadequate data to make any recommendation about using COX inhibitor in practice to prevent preterm labour. Future research should include follow-up of the babies to examine the short-term and long-term effects of COX inhibitors.
CD007525	[ "1546834" ]	[ "Effect of indomethacin on bronchorrhea in patients with chronic bronchitis, diffuse panbronchiolitis, or bronchiectasis." ]	[ "Excessive production of sputum is one of the major symptoms in patients with chronic airway diseases. Because endogenous prostaglandins may play a role in the regulation of airway secretions, blockade of cyclooxygenase pathway with indomethacin could decrease respiratory tract fluid and mucus by inhibiting Cl secretion and glandular secretion and by enhancing Na absorption across airway mucosa. To test this hypothesis, we studied the effect of inhaled indomethacin on bronchorrhea in patients with chronic bronchitis, diffuse panbronchiolitis, and bronchiectasis in a double-blind, placebo-controlled fashion. Patients who inhaled 2 ml of indomethacin (1.2 micrograms/ml) three times a day for 14 days showed a decrease in the amount of sputum, from 189 +/- 19 to 95 +/- 21 g/day (p less than 0.001) and an increase in the solid component of sputum without alterations in parameters of systemic inflammatory responses. Although pulmonary function remained unchanged, perceived dyspnea was improved so that Borg's ratio scale was decreased from 7.1 +/- 0.5 to 4.5 +/- 0.4 (p less than 0.01). Adverse effects, including hypotension and bronchoconstriction, were not observed. The reduction of sputum was accompanied by a significant decrease in the concentrations of prostaglandin (PG)E2, PGF2 alpha, thromboxane B2, and 6-oxo-PGF1 alpha in the sputum. Thus, indomethacin inhalation may be of value in reducing bronchorrhea sputum, probably through the inhibition of PG-dependent airway secretions." ]	There is currently insufficient evidence to support or refute the use of inhaled NSAIDs in the management of bronchiectasis in adults or children. One small trial reported a reduction in sputum production and improved dyspnoea in adults with chronic lung disease who were treated with inhaled indomethacin, indicating that further studies on the efficacy of NSAIDs in treating patients with bronchiectasis are warranted.
CD000940	[ "4073155", "6708033", "9790362" ]	[ "A comparison of ritodrine, terbutaline, and magnesium sulfate for the suppression of preterm labor.", "Comparison of magnesium sulfate, terbutaline and a placebo for inhibition of preterm labor. A randomized study.", "Terbutaline pump maintenance therapy for prevention of preterm delivery: a double-blind trial." ]	[ "Ritodrine, terbutaline, and magnesium sulfate have all been used in the United States as tocolytic drugs. Studies have shown each of these drugs to be effective in suppressing preterm labor. The current study was undertaken in order to compare their relative safety and efficacy and to evaluate the effectiveness of a second drug when the first-used drug failed to stop contractions. No differences in efficacy could be demonstrated between the drugs; however, there was a marked difference in the incidence of maternal side effects. Because of an unacceptable level of side effects, we have stopped the use of terbutaline at our institution.", "Magnesium sulfate has been recommended as a safe and effective agent for inhibiting preterm labor. Its reported adequacy as a tocolytic agent, however, has not been substantiated by randomized, controlled trials. To assess the efficacy of magnesium sulfate, we initiated a prospective, randomized study comparing the capabilities of magnesium sulfate, terbutaline and a placebo (5% dextrose in lactated Ringer's solution) for labor inhibition. The study population consisted of 54 patients between 26 and 34 weeks of gestation and in preterm labor. The diagnosis of labor was made if, following hydration, persistent uterine contractions occurred at a frequency of at least three in a ten-minute period and cervical examination suggested active labor. Success was defined as postponement of delivery for at least 48 hours after initiation of therapy. Despite a trend toward increased efficacy in the terbutaline group there were no significant differences between the three treatment groups with regard to capability of delaying delivery at least 48 hours. Also, there were no significant differences between the groups with regard to gestational age at delivery, birth weight and neonatal survival. The fact that delivery occurred in less than 48 hours of approximately one-half the patients under the best of circumstances emphasizes the need for more effective techniques for the inhibition of preterm labor and the need for a better understanding of the mechanisms involved in the initiation of preterm labor.", "This study's aim was to determine whether maintenance therapy with terbutaline administered by pump prolongs gestation in women after treatment with intravenous magnesium sulfate tocolysis for suspected preterm labor.\n Consenting women with a singleton gestation and intact membranes who had uterine contractions and >1 cm cervical dilation, 80% effacement, or progressive cervical change and whose contractions were successfully arrested with intravenous magnesium were randomly assigned to receive either terbutaline or normal saline solution placebo by subcutaneous infusion pump. Pump therapy was administered with a standardized protocol. Pump therapy was discontinued and parenteral magnesium was resumed if recurrent preterm labor developed while women were on the therapeutic regimen at <34 weeks' gestation and no contraindication for tocolysis existed. If recurrent labor was arrested, pump therapy was restarted according to the original treatment group. A sample size of 48 women was required to detect a 2-week intergroup difference in mean time to delivery. Analyses were based on intent to treat.\n Fifty-two women received terbutaline (n = 24) or placebo (n = 28). At random assignment the groups were similar with respect to age, race, parity, previous preterm delivery, gestational age, and cervical examination. Overall there was a 1-day difference in mean time to delivery between the groups (terbutaline 29 +/- 22 days and placebo 28 +/- 23 days, P = .78). There were no differences in the rates of preterm delivery at <34 and <37 weeks' gestation. Neonatal outcomes were similar.\n Maintenance terbutaline therapy administered by pump does not prolong gestation in women successfully treated for suspected preterm labor." ]	There is not enough evidence to show any difference between magnesium maintenance therapy compared with either placebo or no treatment, or alternative therapies (ritodrine or terbutaline) in preventing preterm birth after an episode of threatened preterm labour.
CD007429	[ "2684990", "19501292" ]	[ "The management of acute acromioclavicular dislocation. A randomised prospective controlled trial.", "Conservative versus surgical treatment for repair of the medial patellofemoral ligament in acute dislocations of the patella." ]	[ "In a prospective study, 60 patients with acute acromioclavicular dislocation were randomly allocated to treatment with a broad arm sling or to reduction and fixation with a coracoclavicular screw. Of these 54 were followed for four years. Conservatively-treated patients regained movement significantly more quickly and fully, returned to work and sport earlier and had fewer unsatisfactory results than those having early operation. For severe dislocations, with acromioclavicular displacement of 2 cm or more, early surgery produced better results. Conservative management is best for most acute dislocations, but younger patients with severe displacement may benefit from early reduction and stabilisation.", "The objective of this study was to analyze and compare the results obtained after 2 types of treatment, surgical and conservative, for acute patellar dislocations.\n We divided 33 patients with acute patellar dislocations into 2 groups. One group with 16 patients underwent conservative treatment (immobilization and subsequent physiotherapy), and the other group with 17 patients underwent surgical treatment. A radiographic examination was performed in the evaluation of the patients to verify predisposing factors for patellofemoral instability, and the Kujala questionnaire was applied with the intention of analyzing the improvement of pain and quality of life. The chi(2) test, t test, and Fisher test were used in the statistical evaluation. A significance level of P < .05 was adopted.\n The groups were considered parametric in relation to age and sex. The conservative treatment group exhibited a higher number of recurrent dislocations (8 patients) than the surgical treatment group, which did not have any relapses. In addition, the surgical treatment group obtained a better mean score on the Kujala test (92) than the conservative treatment group (69).\n We conclude that surgical treatment afforded better results. There were no recurrences in the surgical treatment group, but there were 8 recurrences in the conservative treatment group. The mean Kujala score was 92 in the surgical treatment group and 69 in the conservative treatment group.\n Level II, lesser-quality therapeutic randomized controlled trial." ]	There is insufficient evidence from randomised controlled trials to determine when surgical treatment is indicated for acromioclavicular dislocation in adults in current practice. Sufficiently powered, good quality, well-reported randomised trials of currently-used surgical interventions versus conservative treatment for well-defined injuries are required.
CD000319	[ "9589535", "10685817", "1985618", "2278545", "16750294", "9168289", "16052120", "18048857", "16864815", "1832209", "16340597", "8213020", "16249829", "17265030", "7726351", "19375681", "9704373", "2934803", "18164334", "16351673", "3302924", "11932085", "15372199", "2528826" ]	[ "High-dose methylprednisolone prevents extensive sick leave after whiplash injury. A prospective, randomized, double-blind study.", "Treatment of whiplash associated neck pain [corrected] with botulinum toxin-A: a pilot study.", "Corticosteroid injections in adhesive capsulitis: investigation of their value and site.", "A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study.", "Efficacy and safety of a single botulinum type A toxin complex treatment (Dysport) for the relief of upper back myofascial pain syndrome: results from a randomized double-blind placebo-controlled multicentre study.", "Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study.", "Evidence against trigger point injection technique for the treatment of cervicothoracic myofascial pain with botulinum toxin type A.", "Intramuscular botulinum toxin-A reduces hemiplegic shoulder pain: a randomized, double-blind, comparative study versus intraarticular triamcinolone acetonide.", "A double-blind, controlled study of botulinum toxin A in chronic myofascial pain.", "A controlled trial of corticosteroid injections into facet joints for chronic low back pain.", "The effect of small doses of botulinum toxin a on neck-shoulder myofascial pain syndrome: a double-blind, randomized, and controlled crossover trial.", "Cervical epidural steroid injection for cervicobrachialgia.", "A novel approach of local corticosteroid injection for the treatment of carpal tunnel syndrome.", "High-dose intravenous methylprednisolone in recent traumatic optic neuropathy; a randomized double-masked placebo-controlled clinical trial.", "Intraarticular lidocaine versus intravenous analgesic for reduction of acute anterior shoulder dislocations. A prospective randomized study.", "Intra-articular botulinum toxin A for refractory shoulder pain: a randomized, double-blinded, placebo-controlled trial.", "A randomized, double-blind, prospective pilot study of botulinum toxin injection for refractory, unilateral, cervicothoracic, paraspinal, myofascial pain syndrome.", "Injection of steroids and local anaesthetics as therapy for low-back pain.", "Therapeutic use of botulinum toxin type A in treating neck and upper-back pain of myofascial origin: a pilot study.", "Single vs. two steroid injections for carpal tunnel syndrome: a randomised clinical trial.", "Intravenous methylprednisolone efficacy in status asthmaticus of childhood.", "Comparative study of intra-articular lidocaine and intravenous meperidine/diazepam for shoulder dislocations.", "Comparison of lidocaine injection, botulinum toxin injection, and dry needling to trigger points in myofascial pain syndrome.", "A prospective, randomized, double-blind evaluation of trigger-point injection therapy for low-back pain." ]	[ "A prospective, randomized, double-blind study comparing high-dose methylprednisolone with placebo.\n To evaluate the efficacy of high-dose methylprednisolone when administered within 8 hours after whiplash injury.\n Whiplash injury often results in chronic symptoms. The management of whiplash injuries is controversial, and pharmacologic therapy has received little evaluation. In recent reports, dysfunction of the central nervous system has been indicated in several cases. Methylprednisolone administered within 8 hours after the injury to patients with acute spinal cord injury has been demonstrated to improve the outcome. This procedure was also adopted in a randomized study of cases of whiplash injury in car accidents.\n Forty patients, 22 men and 18 women with a mean age of 35 years (range, 19-65), were included in the study, 20 in each of two groups. They were treated for whiplash injury, which they had sustained in car accidents. The patients were enrolled if their diagnoses were complete and treatment had begun within 8 hours after injury. Disabling symptoms severe enough to prevent the patient from returning to work, number of sick days before and after injury, and sick-leave profile after injury were used as parameters for the evaluation of the effects of the treatment. Baseline demographic data were controlled for when statistical analysis had been performed.\n At the follow-up examination 6 months after initial treatment, there was a significant difference in disabling symptoms between the actively treated patients and the placebo group (P = 0.047), total number of sick days (P = 0.01), and sick-leave profile (P = 0.003).\n The results of this study indicate that acute treatment with high-dose methylprednisolone may be beneficial in preventing extensive sick leave after whiplash injury. However, the number of patients studied was small, and therefore further prospective, controlled studies are needed.", "Up to 87% of patients with whiplash associated disorder (WAD) have some degree of muscle spasm that is contributory to both pain and dysfunction. Botulinum toxin A (BTX-A) produces prolonged muscle relaxation that is dose-dependent and can be easily targeted to affected muscles. BTX-A therapy may be an effective form of therapy offering an alternative or adjunct to conventional modalities. We investigated BTX-A as therapy in patients with WAD.\n This randomized, double blind, placebo controlled study compares outcome measures in 26 patients with chronic neck pain (WAD-II chronic) subsequent to a motor vehicle accident. One-half of the patients received 100 units BTX-A, diluted in 1 ml saline, while the other half received just saline (1 ml). Five trigger points received 0.2 ml each of injectant via a 30 gauge needle. Outcome measures included total subjective neck, shoulder, and head pain based on visual analog scales; objective total range of neck motion (ROM), and the Vernon-Mior subjective function index. Followup assessments were carried out at 2 and 4 weeks post-treatment.\n Fourteen subjects receiving BTX-A and 12 receiving saline completed the study. The treatment group showed a trend toward improvement in ROM and reduction in pain at 2 weeks post-injection. At 4 weeks post-injection the treatment group was significantly improved from preinjection levels (p < 0.01). The placebo group showed no statistically significant changes at any post-treatment time. The Vernon-Mior scale revealed a trend to improvement for both groups.\n BTX-A treatment of subjects with chronic WAD II neck pain resulted in a significant (p < 0.01) improvement in ROM and subjective pain compared to a placebo group, but only a trend to improvement in subjective functioning.", "Forty-eight patients with frozen shoulder for less than six months were assigned at random to receive three shoulder injections into the subacromial bursa or glenohumeral joint at weekly intervals. The treatment groups were (1) intra-articular methylprednisolone and lidocaine, (2) intrabursal methylprednisolone and lidocaine, (3) intra-articular lidocaine, (4) intrabursal lidocaine. The same physical therapy program was carried out for all patients. Assessments of pain and range of motion were performed by a physical therapist who was uninformed about the nature of the injection therapy. There was no significant difference in outcome between intrabursal injection and intra-articular injection. Injection of steroid with lidocaine had no advantage over lidocaine alone in restoring shoulder motion, but partial, transient pain relief occurred in two thirds of the steroid-treated patients.", "Studies in animals indicate that methylprednisolone and naloxone are both potentially beneficial in acute spinal-cord injury, but whether any treatment is clinically effective remains uncertain. We evaluated the efficacy and safety of methylprednisolone and naloxone in a multicenter randomized, double-blind, placebo-controlled trial in patients with acute spinal-cord injury, 95 percent of whom were treated within 14 hours of injury. Methylprednisolone was given to 162 patients as a bolus of 30 mg per kilogram of body weight, followed by infusion at 5.4 mg per kilogram per hour for 23 hours. Naloxone was given to 154 patients as a bolus of 5.4 mg per kilogram, followed by infusion at 4.0 mg per kilogram per hour for 23 hours. Placebos were given to 171 patients by bolus and infusion. Motor and sensory functions were assessed by systematic neurological examination on admission and six weeks and six months after injury. After six months the patients who were treated with methylprednisolone within eight hours of their injury had significant improvement as compared with those given placebo in motor function (neurologic change scores of 16.0 and 11.2, respectively; P = 0.03) and sensation to pinprick (change scores of 11.4 and 6.6; P = 0.02) and touch (change scores, 8.9 and 4.3; P = 0.03). Benefit from methylprednisolone was seen in patients whose injuries were initially evaluated as neurologically complete, as well as in those believed to have incomplete lesions. The patients treated with naloxone, or with methylprednisolone more than eight hours after their injury, did not differ in their neurologic outcomes from those given placebo. Mortality and major morbidity were similar in all three groups. We conclude that in patients with acute spinal-cord injury, treatment with methylprednisolone in the dose used in this study improves neurologic recovery when the medication is given in the first eight hours. We also conclude that treatment with naloxone in the dose used in this study does not improve neurologic recovery after acute spinal-cord injury.", "Botulinum type A toxin (BoNT-A) has antinociceptive and muscle-relaxant properties and may help relieve the symptoms of myofascial pain syndrome. In this study we evaluated the efficacy and tolerability of BoNT-A (Dysport) in patients with myofascial pain syndrome of the upper back. We conducted a prospective, randomized, double-blind, placebo-controlled, 12-week, multicentre study. Patients with moderate-to-severe myofascial pain syndrome affecting cervical and/or shoulder muscles (10 trigger points, disease duration 6-24 months) were randomized to Dysport or saline. Injections were made into the 10 most tender trigger points (40 units per site). The primary outcome was the proportion of patients with mild or no pain at week 5. Secondary outcomes included changes in pain intensity and the number of pain-free days per week. Tolerability and safety were also assessed. At week 5, significantly more patients in the Dysport group reported mild or no pain (51%), compared with the patients in the placebo group (26%; p=0.002). Compared with placebo, Dysport resulted in a significantly greater change from baseline in pain intensity during weeks 5-8 (p<0.05), and significantly fewer days per week without pain between weeks 5 and 12 (p=0.036). Treatment was well tolerated, with most side effects resolving within 8 weeks. In conclusion, in patients with upper back myofascial pain syndrome, injections of 400 Ipsen units of Dysport at 10 individualised trigger points significantly improved pain levels 4-6 weeks after treatment. Injections were well tolerated.", "To compare the efficacy of methylprednisolone administered for 24 hours with methyprednisolone administered for 48 hours or tirilazad mesylate administered for 48 hours in patients with acute spinal cord injury.\n Double-blind, randomized clinical trial.\n Sixteen acute spinal cord injury centers in North America.\n A total of 499 patients with acute spinal cord injury diagnosed in National Acute Spinal Cord Injury Study (NASCIS) centers within 8 hours of injury.\n All patients received an intravenous bolus of methylprednisolone (30 mg/kg) before randomization. Patients in the 24-hour regimen group (n=166) received a methylprednisolone infusion of 5.4 mg/kg per hour for 24 hours, those in the 48-hour regimen group (n=167) received a methylprednisolone infusion of 5.4 mg/kg per hour for 48 hours, and those in the tirilazad group (n=166) received a 2.5 mg/kg bolus infusion of tirilazad mesylate every 6 hours for 48 hours.\n Motor function change between initial presentation and at 6 weeks and 6 months after injury, and change in Functional Independence Measure (FIM) assessed at 6 weeks and 6 months.\n Compared with patients treated with methylprednisolone for 24 hours, those treated with methylprednisolone for 48 hours showed improved motor recovery at 6 weeks (P=.09) and 6 months (P=.07) after injury. The effect of the 48-hour methylprednisolone regimen was significant at 6 weeks (P=.04) and 6 months (P=.01) among patients whose therapy was initiated 3 to 8 hours after injury. Patients who received the 48-hour regimen and who started treatment at 3 to 8 hours were more likely to improve 1 full neurologic grade (P=.03) at 6 months, to show more improvement in 6-month FIM (P=.08), and to have more severe sepsis and severe pneumonia than patients in the 24-hour methylprednisolone group and the tirilazad group, but other complications and mortality (P=.97) were similar. Patients treated with tirilazad for 48 hours showed motor recovery rates equivalent to patients who received methylprednisolone for 24 hours.\n Patients with acute spinal cord injury who receive methylprednisolone within 3 hours of injury should be maintained on the treatment regimen for 24 hours. When methylprednisolone is initiated 3 to 8 hours after injury, patients should be maintained on steroid therapy for 48 hours.", "Traditional strategies for myofascial pain relief provide transient, incomplete, variable, or unpredictable outcomes. Botulinum toxin is itself an analgesic but can also cause sustained muscular relaxation, thereby possibly affording even greater relief than traditional therapies.\n The study goal was to determine whether direct injection of botulinum toxin type A (BoNT-A) into trigger points was efficacious for cervicothoracic myofascial pain, and if so, to determine the presence or absence of a dose-response relation. One hundred thirty-two patients with cervical or shoulder myofascial pain or both and active trigger points were enrolled in a 12-week, randomized, double-blind, placebo-controlled trial. After a 2-week washout period for all medications, patients were injected with either saline or 10, 25, or 50 U BoNT-A into up to five active trigger points. The maximum doses in each experimental group were 0, 50, 125, and 250 U per patient, respectively. Patients subsequently received myofascial release physical therapy and amitriptyline, ibuprofen, and propoxyphene-acetaminophen napsylate. Follow-up visits occurred at 1, 2, 4, 6, 8, and 12 weeks. Outcome measures included visual analog pain scores, pain threshold as measured by pressure algometry, and rescue dose use of propoxyphene-acetaminophen napsylate.\n No significant differences occurred between placebo and BoNT-A groups with respect to visual analog pain scores, pressure algometry, and rescue medication.\n Injection of BoNT-A directly into trigger points did not improve cervicothoracic myofascial pain. The role of direct injection of trigger points with BoNT-A is discussed in comparison to other injection methodologies in the potential genesis of pain relief.", "Shoulder pain is frequent after stroke and interferes with the rehabilitative process and outcome. However, treatments used for hemiplegic shoulder pain are limited and largely ineffective. This prospective, randomized, double-blind controlled study was conducted to compare the efficacies of botulinum toxin type A (BoNT-A) and triamcinolone acetonide (TA) on hemiplegic shoulder pain and their effects on arm function in patients with stroke.\n Twenty-nine hemiplegic stroke patients with shoulder pain (duration <or=24 months, pain on numeric rating scale >or=6/10) were randomized into 2 groups. One group received intramuscular injections of BoNT-A (BOTOX 100 U total) during one session to the infraspinatus, pectoralis and subscapularis muscles in conjunction with an intraarticular injection of normal saline to painful shoulder joint, whereas the other group received an intraarticular injection of TA (40 mg) and an intramuscular injection of normal saline to the same muscles. Outcome measures were pain (measured using a numeric rating scale), physician's global rating scale, shoulder range of motion (ROM) in 4 directions, arm function measured using Fugl-Meyer score, and spasticity measured using the modified Ashworth scale. Measurements were made at baseline and 2, 6, and 12 weeks after injection.\n At 12 weeks after treatment mean decrease in pain was 4.2 in the BoNT-A-treated group versus 2.5 in the TA-treated group (P=0.051), and improvements in overall ROM were 82.9 degrees versus 51.8 degrees in these groups (P=0.059), showing a strong trend toward there being less pain and better ROM among those treated with BoNT-A than with TA. However, no significant differences were observed between the 2 groups in terms of improvement in physician global rating, Fugl-Meyer score or modified Ashworth scales. No adverse effect was observed in either group.\n Results from this study suggest that injection of BoNT-A into selected muscles of the shoulder girdle might provide more pain relief and ROM improvement than intraarticular steroid in patients with hemiplegic shoulder pain. A larger clinical trial needs to be undertaken to confirm the benefits of this approach.", "Recent studies have reported a potential analgesic effect of botulinum toxin A (BTXA) in musculoskeletal pain. The present double-blind, randomized, placebo-controlled, parallel clinical trial studied the effect of BTXA on pain from muscle trigger points and on EMG activity at rest and during voluntary contraction.\n Thirty patients with trigger points in the infraspinatus muscles received either 50 units/0.25 mL of BTXA or 0.25 mL of isotonic saline. Baseline measures were determined during a run-in period of 1 week. Outcome measures including local and referred spontaneous pain, pain detection and tolerance thresholds to mechanical pressure, and shoulder movement were assessed at 3 and 28 days after injection. The interference pattern of the EMG during maximal voluntary effort of infraspinatus muscle was recorded and a standardized search for spontaneous electrical motor endplate activity at the trigger points was performed before and 28 days after BTXA or saline injection.\n BTXA reduced motor endplate activity and the interference pattern of EMG significantly but had no effect on either pain (spontaneous or referred) or pain thresholds compared with isotonic saline.\n The results do not support a specific antinociceptive and analgesic effect of botulinum toxin A.", "Chronic low back pain is a common problem with many treatments, few of which have been rigorously evaluated. This randomized, placebo-controlled trial was designed to evaluate the efficacy of injections of corticosteroid into facet joints to treat chronic low back pain.\n Patients with chronic low back pain who reported immediate relief of their pain after injections of local anesthetic into the facet joints between the fourth and fifth lumbar vertebrae and the fifth lumbar and first sacral vertebrae were randomly assigned to receive under fluoroscopic guidance injections of either methylprednisolone acetate (20 mg; n = 49) or isotonic saline (n = 48) in the same facet joints. Ninety-five patients were followed for six months and their condition assessed with scales of pain severity, back mobility, and limitation of function.\n After one month, none of the outcome measures evaluating pain, functional status, and back flexion differed clinically or statistically between the two study groups. Forty-two percent of the patients who received methylprednisolone and 33 percent of those who received placebo reported marked or very marked improvement (95 percent confidence interval for the difference, -11 to 28 percentage points; P = 0.53). The results were similar after three months. At the six-month evaluation, the patients treated with methylprednisolone reported more improvement, less pain on the visual-analogue scale, and less physical disability. The differences were reduced, however, when concurrent interventions were taken into account. Moreover, only 11 patients (22 percent) in the methylprednisolone group and 5 (10 percent) in the placebo group had sustained improvement from the first month to the sixth month (95 percent confidence interval for the difference, -2 to 26; P = 0.19).\n We conclude that injecting methylprednisolone acetate into the facet joints is of little value in the treatment of patients with chronic low back pain.", "Myofascial pain syndrome is a common cause of muscular pain in the shoulder-neck region. Injections of large amounts of botulinum toxin A have been found to be beneficial for the alleviation of myofascial pain, but large doses of this toxin may cause paresis of the muscle and other adverse events. The aim of this work was to determine the effect of small doses (5 U) of botulinum toxin A (BTA) injected directly into the painful trigger points of the muscles, using a double-blind crossover technique.\n On the basis of the empirical criteria proposed for diagnosis of myofascial pain syndrome, 31 patients suffering from myofascial pain in the neck-shoulder region were studied. The patients received either botulinum toxin A or physiological saline injections on 2 occasions 4 weeks apart. The total dose varied from 15 to 35 U of botulinum toxin A [28+/- 6 U (mean+/- SD)]. The follow-up measurements were carried out at 4 weeks after each treatment. Neck pain and result of treatment were assessed with questionnaires. The pressure pain threshold was determined using a dolorimeter.\n Neck pain values decreased from 4.3+/- 2.4 to 3.3+/- 2.0 after saline injections and from 4.1+/- 2.1 to 3.3+/- 2.2 after botulinum toxin A. The pressure pain threshold values increased from 5.2+/-1.6 to 5.9+/-1.5 and from 5.7+/-1.6 to 5.9+/-1.6 after injections with saline and botulinum toxin A, respectively. No statistically significant changes in the neck pain and pressure pain threshold values occurred between the botulinum toxin A and saline groups. After the first injections, the subjective result of treatment was significantly (P=0.008) in favor of botulinum toxin A, and after the second injections, the subjective result was better for saline, but the difference was not statistically significant (P=0.098). There was no significant difference in the prevalence of side effects between saline and botulinum toxin A.\n Our study shows that there was no difference between the effect of small doses of botulinum toxin A and those of physiological saline in the treatment of myofascial pain syndrome.", "Fifty patients with chronic resistant cervicobrachialgia were randomly divided into two groups. Twenty-five patients (group A) were treated with cervical epidural steroid/lidocaine injections and 17 patients (group B) were treated with steroid/lidocaine injections into the posterior neck muscles. Another eight patients from group B were excluded from the study because they had started the process of litigation of insurance claims and their subjective analysis of pain relief might therefore not be trustworthy. One to three injections were administered at 2-week intervals according to the clinical response. All patients continued their various pre-study treatments: non-steroidal anti-inflammatory drugs, non-opioid analgesics and physiotherapy. Pain relief was evaluated by the visual analogue scale 1 week after the last injection and then 1 year later. One week after the last injection we rated pain relief as very good and good in 76% of the patients in group A, as compared to 35.5% of the patients in group B. One year after the treatment 68% of the group A patients still had very good and good pain relief, whereas only 11.8% of group B patients reported this degree of pain relief. These differences were statistically significant. We failed to achieve significant improvement of tendon reflexes or of sensory loss in both groups, but the increase in the range of motion, the fraction of patients who were able to decrease their daily dose of analgesics, and recovery of the capacity for work were significantly better in group A. We encountered no complications in either group of patients.(ABSTRACT TRUNCATED AT 250 WORDS)", "The objective of the study was to compare the favorable response rate, time duration, and pain level of local corticosteroid injection using a novel approach for the treatment of carpal tunnel syndrome vs a classic approach. Patients with symptomatic carpal tunnel syndrome of less than 1-year duration were randomized for local corticosteroid injection using either the classic approach or a novel approach. In our approach (novel), we used a 29 gauge x 1/2-in. needle and a 1-ml insulin syringe containing 12 mg of methylprednisolone mixed with 0.15 ml of lidocaine 2%, and the site of the injection was 2-3 cm distal to the middle of wrist crease. In the classic approach, we used a 25 gauge x 3-cm needle and a 2-ml syringe injecting 35 mg of methylprednisolone mixed with 0.5 ml of lidocaine 2%, 3-4 cm proximal to the wrist crease and just ulnar to the tendon of the flexor carpi radialis muscle. Response rate was evaluated 1, 3, 6, and 12 weeks after the injection, and also the duration of time of the procedure and the level of pain using the visual analogue scale were compared between the two groups. Forty-two patients signed the consent form, and all of them completed the study [21 patients in the classic approach group (group 1) and 21 patients in the novel approach group (group 2)]. The favorable response rates were 100, 81, 71, and 57% in group 1 and 100, 71, 67, and 57% in group 2 after 1, 3, 6, and 12 weeks, respectively. There was no significant difference in the favorable response rate between the two groups (p=0.468, 95% CI=-12-31%, after 3 weeks). The average duration of time of the procedure in group 1 was 26.71+/-32.83 s compared to 8.48+/-1.123 s (p=0.021) in group 2. The average grade of pain expressed by the patients in group 1 was 4.38+/-1.523 compared to 3.62+/-1.071 in group 2 (p=0.065). In conclusion, local corticosteroid injection using the novel approach for the treatment of carpal tunnel syndrome is helpful, and the favorable response rates are comparable to those using the classic approach after 1, 3, 6, and 12 weeks. The novel approach is much less time consuming and is not more painful.", "To compare the effect of high-dose intravenous corticosteroid therapy with placebo in the treatment of recent traumatic optic neuropathy (TON).\n In a double-masked placebo-controlled clinical trial, 31 eyes of 31 patients were randomly assigned to two groups. Patients with history of trauma < or =7 days were included. Unconscious patients, eyes with penetrating trauma and candidates for decompression surgery were excluded. The treatment group (16 eyes) received 250 mg methylprednisolone intravenously every 6 h for 3 days, then 1 mg/kg prednisolone orally for 14 days; the placebo group (15 eyes) received 50 ml normal saline intravenously every 6 h for 3 days, then placebo for 14 days. Visual improvement was considered as a decrease of at least 0.4 logMAR in final visual acuity.\n Mean final BCVA (best corrected visual acuity) in the treatment group was 1.11+/- 1.14 and the placebo group was 1.78 +/- 1.23. This difference was not significant (P = 0.13). Visual acuity was improved in 68.8% of the treatment group and 53.3% of the placebo group, but the difference was not statistically significant (P = 0.38). The difference between initial and final BCVA in both groups was determined to be statistically significant (P < 0.001 and 0.010 respectively).\n Our study confirms earlier findings that there is no difference in visual acuity improvement between intravenous high-dose corticosteroids and placebo in treatment of recent TNO.", "We performed a prospective, randomized study to evaluate the use of injected lidocaine as an anesthetic for closed reduction of acute anterior shoulder dislocations. Thirty consecutive patients who presented at the emergency department with acute anterior shoulder dislocations were randomly placed in one of two groups. One group received an intraarticular injection of 20 ml of 1% lidocaine and the other group, intravenous injections of morphine sulfate and midazolam. The groups were compared regarding time of reduction maneuver, difficulty of reduction, subjective pain, complications, and total time spent in the emergency department. The lidocaine provided adequate anesthesia and secondary relief of muscle spasm in 15 of 15 (100%) patients. When compared with the intravenous sedation group, the lidocaine group showed no statistically significant difference in time for reduction maneuver, difficulty of reduction, or subjective pain. The lidocaine group had no complications and had a statistically significant shorter emergency department visit when compared with the intravenous sedation group (mean, 78 minutes versus 186 minutes; P = 0.004). Lidocaine provides excellent anesthesia for patients with uncomplicated anterior shoulder dislocations and can be very beneficial when sedation is contraindicated. Lidocaine injections also proved to be cost effective in our institution, reducing total costs by as much as 62%.", "We compared the short-term efficacy and safety of intra-articular (IA) botulinum toxin A (BoNT/A) to IA-placebo in patients with chronic, refractory shoulder joint pain. Forty-three shoulder joints in patients with moderate-to-severe shoulder arthritis pain were randomized to receive (1) 100 units IA-BoNT/A + lidocaine or (2) IA-saline + lidocaine. The following outcomes were compared using analysis of covariance: (1) primary: change in pain severity on a visual analog scale at 1 month (VAS, 0 cm to 10 cm); (2) secondary: Shoulder Pain and Disability Index (SPADI) disability subscale, quality of life on short-form (SF)-36 subscales, percent of patients who achieved at least a 30% decrease or a 2-point reduction in VAS pain (clinically meaningful pain relief), and safety. Both BoNT/A (n = 21) and placebo (n = 22) groups were comparable at baseline. At 1 month post-injection, the VAS pain reduction was significantly more in the BoNT/A group versus the placebo group (-2.4 vs -0.8; P-value = 0.014). When comparing BoNT/A with the placebo group at 1 month, it was observed that 5 SF-36 subscale scores improved significantly (P </= 0.035), and the SPADI disability improved more with a trend toward significance (51.5 +/- 4.4 vs 64.9 +/- 3.9; P = 0.083). In addition, clinically meaningful pain relief occurred in 61% versus 36% patients (P = 0.22). The total number of adverse events was similar, which included 50 events in the BoNT/A group versus 46 events in the placebo group. A single injection of BoNT/A produced statistically significant and clinically meaningful pain relief and improvement in quality of life in patients with chronic refractory moderate/severe shoulder arthritis pain at 1 month. These data provide evidence to support the efficacy of this novel neurotoxin therapy that needs to be confirmed in a multicenter, randomized trial.", "In a randomized, double-blind study, two dosage strengths of botulinum toxin type A were compared with normal saline injected into symptomatic trigger points in the cervicothoracic paraspinal muscles.\n To compare the effect of botulinum toxin type A injections with that of normal saline to determine the former's usefulness in the management of neck pain and disability.\n The results of several studies have suggested that botulinum toxin type A may reduce pain associated with myofascial pain syndromes.\n Thirty-three participants were divided randomly to receive either 50 or 100 units of botulinum toxin type A, or normal saline. Patients were re-evaluated over a 4-month period by assessment of their pain and disability and pressure algometer readings, and then offered a second injection of 100 units of botulinum toxin type A.\n All three groups showed significant treatment effects as measured by a decline in the scores on the Neck Pain and Disability Visual Analogue Scale and an increase in the pressure algometer scores. Group differences were apparent only when the authors considered the number of patients who were asymptomatic as a result of the injections.\n Although no statistically significant benefit of botulinum toxin type A over placebo was demonstrated in this study, the high incidence of patients who were asymptomatic after a second injection suggests that further research is needed to determine whether higher dosages and sequential injections in a larger cohort might show a botulinum toxin type A effect.", "Thirty patients with low-back pain of at least one month's duration were included in a double-blind controlled study with third-party administration and treated with either methylprednisolone acetate mixed with lignocaine or isotonic saline, injected at the site of the iliolumbar ligament. The treatment was evaluated by a visual analogue scale, range of spinal flexion ad modum Wright & Moll and of the patients' self-assessments. In the methylprednisolone group, significant decreases in pain score and in patients' self-assessments were found. The range of spinal flexion did not undergo any significant change. No significant changes were found in the control group. No side effects were observed during the study.", "To determine the efficacy of botulinum toxin type A (BTX-A) in treating neck and upper-back pain of myofascial origin.\n A randomized, double-blind, placebo-controlled pilot study.\n Outpatient physical medicine and rehabilitation clinic of a university-affiliated tertiary hospital.\n A total of 29 subjects enrolled from among 45 screened patients. No subject withdrawal due to serious adverse events occurred.\n Subjects were evaluated at baseline, received a 1-time injection of either BTX-A (treatment group) or saline (control group), and were followed up at 2 weeks and at months 1, 2, 3, 4, and 6.\n Visual analog scale (VAS) for pain, the Neck Disability Index (NDI), and the Medical Outcome Study 36-Item Short-Form Health Survey (SF-36).\n Improvements in the VAS and NDI scores were seen in the treatment group but were not significant when compared with the controls. Statistically significant improvements for the treatment group were seen in the SF-36 bodily pain (at months 2 and 4) and mental health (at month 1) scales but not in the other scales, nor in the summary measures. No serious adverse events were reported.\n Trends toward improvements in VAS and NDI scores of the BTX-A group are encouraging, but they were possibly due to a placebo effect and were not statistically significant. The BTX-A subjects, at certain time points, showed statistically significant improvements in the bodily pain and mental health scales of the SF-36 compared with controls. Our study had limited power and population base, but the results could be used to properly power follow-up studies to further investigate this topic.", "We investigated the efficacy of a single vs. double steroid injections in the treatment of carpal tunnel syndrome (CTS) in a randomised double-blind controlled trial. Patients with idiopathic CTS were randomised into (i) one group receiving a baseline methylprednisolone acetate injection plus a saline injection 8 weeks later and (ii) a second group receiving methylprednisolone acetate injection at baseline and at 8 weeks. The primary outcome was the Global Symptom Score (GSS). Forty patients were recruited. By 40 weeks, the mean GSS improved from 25.6 to 14.1 in the single-injection group whereas from 26.7 to 12.6 in the reinjection group, but there was no significant difference in GSS between the two groups (p = 0.26). There were also no significant differences in terms of electrophysiological and functional outcomes. The results suggest that an additional steroid injection confers no added benefit to a single injection in terms of symptom relief.", "Forty-nine nonsteroid-dependent children hospitalized with status asthmaticus were randomized to receive IV placebo or methylprednisolone treatment (1 mg/kg every six hours). All patients received nebulized isoetharine inhalations and continuous IV aminophylline infusion. Twenty-four hours after admission, the methylprednisolone-treated patients demonstrated a greater rate of improvement in their clinical scoring index than did placebo-treated children. However, the duration of hospital stay was not significantly shortened. Twenty-eight of the patients performed serial bedside spirometry at 0, 12, 24, and 36 hours after admission. The methyl-prednisolone-treated patients experienced a more rapid recovery from peripheral airway obstruction as measured by forced expiratory flow rate during 25% to 75% of forced vital capacity (FEF25-75). The magnitude and rate of improvement in FEF25-75 was significantly greater at 36 hours (P less than .05) and independent of changes in peak expiratory flow rate, forced vital capacity, or forced expiratory volume in the first second of forced vital capacity. Placebo-treated patients had a higher incidence of asthma relapse within 4 weeks of discharge (eight v two relapses, P less than .05). Findings of this study indicate that IV corticosteroid therapy is beneficial in treating pediatric status asthmaticus.", "The purpose of this study was to compare the analgesic effectiveness of intra-articular lidocaine versus intravenous meperidine and diazepam during the reduction of anterior shoulder dislocations. Patients were randomized to one of the two methods before the reduction of shoulder dislocations. Patients marked a visual analog pain scale at baseline, after anesthesia just before reduction, and at the time of discharge. Interference with the procedure caused by pain or lack of muscle relaxation, perception of adequacy of analgesia by the patient, adverse effects, and time to discharge from the Emergency Department (ED) were measured. Differences of outcomes, relative risks (RR), and 95% confidence intervals (CIs) were derived. Fifty-four patients with anterior shoulder dislocations presenting from May 21, 1998 through January 21, 1999 were included in this study; 29 were randomly assigned to receive intra-articular lidocaine (IAL) and 25 to receive intravenous meperidine/diazepam (IVMD). IAL was less effective than IVMD in relieving pre-reduction pain (p = 0.045) but equally effective in overall pain relief (p = 0.98). IAL was more effective than IVMD in shortening recovery time (p = 0.025). There was an indication favoring IVMD in terms of physician-perceived muscle relaxation and patient's perception of analgesia adequacy. In conclusion, although the IVMD method appears to have some clinically and statistically significant advantages, IAL possesses some favorable features that render it to be an analgesia alternative in shoulder dislocation reduction.", "Myofascial pain syndrome (MPS) is one of the most common causes of chronic musculoskeletal pain. Several methods have been recommended for the inactivation of trigger points (TrP).\n This prospective, single-blind study was proposed to compare TrP injection with botulinum toxin type A (BTX-A) to dry needling and lidocaine injection in MPS.\n Eighty-seven trigger points (cervical and/or periscapular regions) in 23 female and six male patients with MPS were treated and randomly assigned to three groups: lidocaine injection (n=10, 32 TrP), dry needling (n=10, 33 TrP), and BTX-A injection (n=9, 22 TrP).\n Clinical assessment including cervical range of motion, TrP pain pressure threshold (PPT), pain scores (PS), and visual analog scales for pain, fatigue, and work disability were evaluated at entry and the end of the 4th week. Additionally, depression and anxiety were evaluated with the Hamilton depression and anxiety rating scales, and quality of life was assessed using the Nottingham health profile (NHP). The subjects were also asked to describe side effects. INJECTION PROCEDURE: One milliliter of 0.5% lidocaine was administered to each TrP in the lidocaine injection group, 10-20 IU of BTX-A to each TrP in the BTX-A group, and dry needling to each TrP in the last group, followed by stretching of the muscle groups involved. The patients were instructed to continue their home exercise programs.\n Pain pressure thresholds and PS significantly improved in all three groups. In the lidocaine group, PPT values were significantly higher than in the dry needle group, and PS were significantly lower than in both the BTX-A and dry needle groups. In all, visual analog scores significantly decreased in the lidocaine injection and BTX-A groups and did not significantly change in the dry needle group. Disturbance during the injection procedure was lowest in the lidocaine injection group. Quality of life scores assessed by NHP significantly improved in the lidocaine and BTX-A groups but not in the dry needle group. Depression and anxiety scores significantly improved only in the BTX-A-injected group.\n Injection is more practical and rapid, since it causes less disturbance than dry needling and is more cost effective than BTX-A injection, and seems the treatment of choice in MPS. On the other hand, BTX-A could be selectively used in MPS patients resistant to conventional treatments.", "The efficacy of trigger-point injection therapy in treatment of low-back strain was evaluated in a prospective, randomized, double-blind study. The patient population consisted of 63 individuals with low-back strain. Patients with this diagnosis had nonradiating low-back pain, normal neurologic examination, absence of tension signs, and lumbosacral roentgenograms interpreted as being within normal limits. They were treated conservatively for 4 weeks before entering the study. Injection therapy was of four different types: lidocaine, lidocaine combined with a steroid, acupuncture, and vapocoolant spray with acupressure. Results indicated that therapy without injected medication (63% improvement rate) was at least as effective as therapy with drug injection (42% improvement rate), at a P value of 0.09. Trigger-point therapy seems to be a useful adjunct in treatment of low-back strain. The injected substance apparently is not the critical factor, since direct mechanical stimulus to the trigger-point seems to give symptomatic relief equal to that of treatment with various types of injected medication." ]	The major limitations are the lack of replication of the findings and sufficiently large trials. There is moderate evidence for the benefit of intravenous methylprednisolone given within eight hours of acute whiplash, from a single trial. Lidocaine injection into myofascial trigger points appears effective in two trials. There is moderate evidence that Botulinum toxin A is not superior to saline injection for chronic MND. Muscle relaxants, analgesics and NSAIDs had limited evidence and unclear benefits.
CD001690	[ "9800931" ]	[ "A double-blind randomised placebo controlled trial of postnatal norethisterone enanthate: the effect on postnatal depression and serum hormones." ]	[ "To determine the effect of postnatal administration of the long-acting progestogen contraceptive, norethisterone enanthate, on postnatal depression and on serum hormone concentrations, and their association with depression.\n Double-blind randomised placebo-controlled trial.\n A tertiary care hospital in Johannesburg, South Africa. POPULATION Postnatal women using a non-hormonal method of contraception (n = 180).\n Random allocation within 48 hours of delivery to norethisterone enanthate by injection, or placebo.\n Depression scores in the three months postpartum as rated by the Montgomery-Asberg Depression Rating Scale (MADRS) and the Edinburgh Postnatal Depression Scale (EPDS); 2. serum 17beta-oestradiol, progesterone, testosterone and the 17beta-oestradiol:progesterone ratio at six weeks postpartum.\n There was a chance excess of caesarean section deliveries in the progestogen group. Mean depression scores were significantly higher in the progestogen group than in the placebo group at six weeks postpartum (mean MADRS score 8.3 vs 4.9; P = 0.0111; mean EPDS score 10.6 vs 7.5; P = 0.0022). Mean serum 17beta-oestradiol and progesterone concentrations were significantly lower in the progestogen group compared with the placebo group at six weeks postpartum. There were no correlations between any of the hormone parameters and depression at six weeks except in the formula feeding subgroup of the placebo group, where formula feeding and 17beta-oestradiol concentrations were positively associated with depression.\n Long-acting norethisterone enanthate given within 48 hours of delivery is associated with an increased risk of developing postnatal depression and causes suppression of endogenous ovarian hormone secretion." ]	Synthetic progestogens should be used with significant caution in the postpartum period. The role of natural progesterone in the prevention and treatment of postpartum depression has yet to be evaluated in a randomised, placebo-controlled trial. Oestrogen therapy may be of modest value for the treatment of severe postpartum depression. Its role in the prevention of recurrent postpartum depression has not been rigorously evaluated. Further research is warranted.
CD007358	[ "8988832", "2657675", "6348714", "2813153", "2938471", "1930699", "7541355", "11119198", "9602959" ]	[ "Dose-response of flurbiprofen on postoperative pain and emesis after paediatric strabismus surgery.", "An evaluation of flurbiprofen, aspirin, and placebo in postoperative oral surgery pain.", "Analgesic effect of graded doses of flurbiprofen in post-episiotomy pain.", "Evaluation of flurbiprofen, acetaminophen, an acetaminophen-codeine combination, and placebo in postoperative oral surgery pain.", "Flurbiprofen for the treatment of soft tissue trauma.", "The analgesic efficacy of flurbiprofen compared to acetaminophen with codeine.", "Flurbiprofen local action transcutaneous (LAT): clinical evaluation in the treatment of acute ankle sprains.", "Diclofenac and flurbiprofen with or without clonidine for postoperative analgesia in children undergoing elective ophthalmological surgery.", "Analgesic dose-response relationship of ibuprofen 50, 100, 200, and 400 mg after surgical removal of third molars: a single-dose, randomized, placebo-controlled, and double-blind study of 304 patients." ]	[ "Intravenous flurbiprofen, a non-steroidal antiinflammatory drug (NSAID), has been used recently for postoperative pain relief in adults. The drug is also likely to have antiemetic property. The present study was undertaken to investigate the effect of flurbiprofen on postoperative pain and emesis in children undergoing strabismus surgery, which is well known to produce postoperative nausea and vomiting.\n In a prospective, randomised, controlled clinical trial, 90 children aged 2-11 yr received saline (control), flurbiprofen 0.5 mg.kg-1, or flurbiprofen 1 mg.kg-1. Saline and flurbiprofen were administered i.v. immediately after induction of anaesthesia. Anaesthesia was induced and maintained with sevoflurane and nitrous oxide in oxygen. Postoperative pain was assessed by a blinded observer using an objective pain scale (OPS). No opioids or antiemetics were administered throughout the study. The incidence and frequency of vomiting were compared among groups.\n Flurbiprofen 1 mg.kg-1 provided lower OPS (highest) scores during the eight hours after surgery and a reduced requirement for postoperative supplementary analgesic (diclofenac suppository) compared with the other two regimens. The two doses of flurbiprofen failed to decrease the incidence and frequency of vomiting.\n These data suggest that preoperative flurbiprofen 1 mg.kg-1 iv is a simple and effective approach to postoperative pain relief but not to the prevention of emesis following paediatric strabismus surgery.", "One hundred sixty-four outpatients with postoperative pain after the removal of impacted third molars were randomly assigned on a double-blind basis, to receive oral doses of flurbiprofen 25, 50, or 100 mg; aspirin 600 mg; or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 8 hours after medicating. Estimates of sum of pain differences (SPID), peak pain intensity difference (PID), total relief, peak relief, and hours of 50% relief were derived from these subjective reports. All active medications were significantly superior to placebo. Analgesia was similar for flurbiprofen 25 mg and aspirin 600 mg. Flurbiprofen 50 and 100 mg were significantly superior to aspirin for every measure of analgesia except peak PID. There was a significant dose-response regression between flurbiprofen 25 mg and both of the higher dosages. Flurbiprofen 50 and 100 mg did not differ significantly, suggesting a plateau in flurbiprofen's analgesia. The analgesic effect of flurbiprofen was significant by hour 1 and persisted for 8 hours. The frequency of adverse effects was similar for the active medications.", "Our purpose was to evaluate the analgesic efficacy and safety of single oral doses of flurbiprofen 25, 50 and 100 mg, aspirin 600 mg, and placebo in the relief of moderate to severe post-episiotomy pain. One hundred and fifty-two evaluable patients completed a randomized, double-blind, stratified, parallel groups study. They were observed over a six hour period by one nurse-observer. Based upon each of the summary efficacy measures SPID, TOTAL and PEAK % and most of the hourly direct measures of pain intensity and pain relief, each of the four active treatments were statistically superior to placebo. Flurbiprofen 25 mg appeared to be slightly less effective than aspirin 600 mg, but the differences were not statistically significant. Flurbiprofen 50 and 100 mg were quite similar and were significantly more effective than aspirin 600 mg and flurbiprofen 25 mg. There were no observed or reported adverse effects.", "Eighty-eight outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, to receive a single, oral dose of flurbiprofen 100 mg, acetaminophen 600 mg, a combination of acetaminophen 600 mg with codeine 60 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 12 hours after medicating. Estimates of sum of pain intensity differences, peak pain intensity differences, total relief, peak relief, and hours of 50% relief were derived from these subjective reports. Flurbiprofen and the acetaminophen-codeine combination were significantly superior to placebo for every measure of total and peak analgesia and significantly superior to acetaminophen alone for most measures of efficacy. Based on the 12-hour data, acetaminophen alone did not differ significantly from placebo; however, it was superior to placebo for measures of total effect based on the 4-hour data. Flurbiprofen was significantly superior to the acetaminophen codeine combination with respect to the number of hours until remedication. All medications had manifested an effect by hour 1; analgesia persisted for 12 hours for flurbiprofen, 6 hours for acetaminophen-codeine, and 3 hours for acetaminophen alone. The frequency of adverse effects was similar for the active medications.", "The use of flurbiprofen as an analgesic and anti-inflammatory agent in patients with soft tissue trauma induced by sports injuries, lumbar disk syndrome, or surgery was considered in three clinical trials. In the first study, soft tissue injuries to the lower limb in 51 professional soccer players were treated for six days with 150 mg of flurbiprofen per day or 3.6 g of aspirin per day. The second study compared three weeks of treatment with daily doses of 200 mg of flurbiprofen and 4 g of acetaminophen in 50 patients with acute low back pain. In the third study, 100 postoperative patients were given 400 mg of flurbiprofen per day or 4 g of acetaminophen per day for seven days following total or partial meniscectomy. In all of these trials, flurbiprofen showed excellent analgesic efficacy in reducing pain and swelling, and enhanced the recovery of patients with soft tissue trauma.", "In a single-dose, parallel group, randomized block treatment allocation study, the relative analgesic efficacy of flurbiprofen, a nonsteroidal antiinflammatory drug, was compared to acetaminophen 650 mg with codeine 60 mg, zomepirac sodium 100 mg, and placebo. A total of 226 post-surgical dental patients (146 females and 80 males) participated in the study. Flurbiprofen in 50 mg and 100 mg dosages demonstrated effective analgesic activity with the 100 mg dosage being at least as effective as the acetaminophen/codeine combination. The results of this study support previous work on flurbiprofen.", "One hundred and thirty-one male and female outpatients, aged 18-70 yr, with acute pain in the ankle joint caused by a post-traumatic sprain, entered a multicentre, randomised, double-blind, parallel-group, study. The patients were assigned to a 40 mg flurbiprofen patch (n = 65) or a non-medicated (but otherwise identical) control (n = 66), 12-hourly over 7 days, and were assessed at entry and after 3 and 7 days treatment. On day 7, spontaneous pain (the prime efficacy parameter), as evaluated by the patient on a visual analogue scale in the physician's office, showed significant improvement in the 40 mg flurbiprofen patch group compared to control (change from baseline) (p = 0.039), a result corroborated by the evaluation of the periarticular oedema: a reduction of 77.4% was observed in the 40 mg flurbiprofen patch group, compared with 63.8% in the control group (p = 0.025). The other selected efficacy criteria showed changes with a trend in favour of the 40 mg flurbiprofen patch but without statistical significance. Two mild and local adverse events were reported by two flurbiprofen patch patients, but neither patients discontinued the treatment prematurely. Physicians and patients found the flurbiprofen patch to be efficacious and well tolerated. Compliance was excellent in both groups. The efficacy and tolerability of the 40 mg flurbiprofen patch are therefore confirmed in the treatment of acute ankle sprains.", "We conducted a prospective, randomized study to compare the efficacy of preoperative diclofenac, flurbiprofen, and clonidine, given alone, as well as the combination of diclofenac and clonidine, and flurbiprofen and clonidine in controlling postoperative pain in 125 children. The patients (ASA I, 2-12 years) undergoing elective ophthalmological surgery were allocated to one of five groups: rectal diclofenac 2 mg.kg(-1) following oral placebo premedication, i. v. flurbiprofen 1 mg.kg(-1) following placebo premedication, oral clonidine premedication, rectal diclofenac 2 mg.kg(-1) following clonidine, and i.v. flurbiprofen 1 mg.kg(-1) following clonidine. The children received clonidine (4 microg.kg(-1)) or placebo 105 min before anaesthesia. Diclofenac or flurbiprofen was given immediately after induction of anaesthesia. Anaesthesia was induced and maintained with sevoflurane and nitrous oxide in oxygen. Postoperative pain was assessed by a blinded observer using a modified objective pain scale (OPS). No opioids were administered throughout the study. Rectal diclofenac 2 mg.kg(-1) i.v. flurbiprofen 1 mg.kg(-1), oral clonidine 4 microg.kg(-1) provided similar OPS scores and requirement for supplementary analgesics during 12 h after surgery. Combination of oral clonidine and one of these nonsteroidal analgesics minimized postoperative pain. Our findings suggest that this combined regimen may be a promising prophylactic approach to postoperative pain control in children undergoing ophthalmological surgery.", "The purpose of this single-dose, randomized, placebo-controlled, and double-blind study was to evaluate the analgesic dose-response relationship of 50-mg, 100-mg, 200-mg, and 400-mg doses of ibuprofen after third molar surgery. Patients were instructed to take a single dose of either placebo or 50 mg, 100 mg, 200 mg, or 400 mg of ibuprofen when the postoperative pain was moderate to severe. Acetaminophen 500 mg was used as a rescue medication. Pain intensity, pain relief, and any possible adverse events were recorded on self-administered questionnaires hourly for 6 hours after intake of study medication. If rescue medication was taken, the time of intake was registered. A total of 304 patients entered the study, and 258 complied with the protocol. A positive analgesic dose-response relationship of 50-mg, 100-mg, 200-mg, and 400-mg doses of ibuprofen was observed when evaluated by pain intensity difference, sum of pain intensity difference, pain relief, total pain relief, and survival distribution of patients not taking rescue medication. Although significant pain relief was seen after a dose of 50 mg ibuprofen, ibuprofen 400 mg provided maximum pain relief and the longest duration of analgesic effect. Mild transient adverse events were reported by 6.8% of the patients. However, there was no significant difference in frequency between the placebo and 50 mg, 100 mg, 200 mg, and 400 mg ibuprofen dose groups." ]	Flurbiprofen at doses of 50 mg and 100 mg is an effective analgesic in moderate to severe acute postoperative pain. The NNT for at least 50% pain relief is similar to that of commonly used NSAIDs such as ibuprofen and naproxen at usual doses. Use of rescue medication indicates a duration of action exceeding 6 hours.
CD009052	[ "12547542", "16442954", "19546387", "17692642", "16035095", "15681939", "17382476", "16096533", "17906567", "16035081", "20838118", "15734783", "10475286", "16102099", "9447855", "11413430", "16788315", "15804151", "8832445", "19583608", "9085974", "1377035", "9278654", "17894791", "8792730", "16757825" ]	[ "Effect of recombinant activated factor VII on perioperative blood loss in patients undergoing retropubic prostatectomy: a double-blind placebo-controlled randomised trial.", "Safety and hemostatic effect of recombinant activated factor VII in cirrhotic patients undergoing partial hepatectomy: a multicenter, randomized, double-blind, placebo-controlled trial.", "Safety and efficacy of recombinant activated factor VII: a randomized placebo-controlled trial in the setting of bleeding after cardiac surgery.", "Activated recombinant factor VII in orthotopic liver transplantation.", "Efficacy and safety of repeated perioperative doses of recombinant factor VIIa in liver transplantation.", "Recombinant coagulation factor VIIa in major liver resection: a randomized, placebo-controlled, double-blind clinical trial.", "Recombinant FVIIa decreases perioperative blood transfusion requirement in burn patients undergoing excision and skin grafting--results of a single centre pilot study.", "Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: two parallel randomized, placebo-controlled, double-blind clinical trials.", "Recombinant activated factor VII in spinal surgery: a multicenter, randomized, double-blind, placebo-controlled, dose-escalation trial.", "Safety and efficacy of a single bolus administration of recombinant factor VIIa in liver transplantation due to chronic liver disease.", "Results of the CONTROL trial: efficacy and safety of recombinant activated Factor VII in the management of refractory traumatic hemorrhage.", "Use of activated recombinant coagulation factor VII in patients undergoing reconstruction surgery for traumatic fracture of pelvis or pelvis and acetabulum: a double-blind, randomized, placebo-controlled trial.", "Reduction of blood loss and transfusion requirement by aprotinin in posterior lumbar spine fusion.", "Recombinant activated factor VII in treatment of bleeding complications following hematopoietic stem cell transplantation.", "Aprotinin decreases blood loss and homologous transfusions in patients undergoing major orthopedic surgery.", "The efficacy of antifibrinolytics in the reduction of blood loss during complex adult reconstructive spine surgery.", "Elective administration in infants of low-dose recombinant activated factor VII (rFVIIa) in cardiopulmonary bypass surgery for congenital heart disease does not shorten time to chest closure or reduce blood loss and need for transfusions: a randomized, double-blind, parallel group, placebo-controlled study of rFVIIa and standard haemostatic replacement therapy versus standard haemostatic replacement therapy.", "Combination of acute preoperative plateletpheresis, cell salvage, and aprotinin minimizes blood loss and requirement during cardiac surgery.", "The efficacy of single-dose aprotinin 2 million KIU in reducing blood loss and its impact on the incidence of deep venous thrombosis in patients undergoing total hip replacement surgery.", "Thromboelastography-based transfusion algorithm reduces blood product use after elective CABG: a prospective randomized study.", "Aprotinin reduces blood loss in patients undergoing elective liver resection.", "Reduction in blood loss and blood use after cardiopulmonary bypass with high-dose aprotinin versus autologous fresh whole blood transfusion.", "Prospective randomized placebo-controlled trial of aprotinin for elective aortic reconstruction.", "A multicenter pilot-randomized controlled trial of the feasibility of an augmented red blood cell transfusion strategy for patients treated with induction chemotherapy for acute leukemia or stem cell transplantation.", "Autologous blood transfusion in hip replacement. No effect on blood loss but less increase of plasminogen activator inhibitor in a randomized series of 80 patients.", "Recombinant activated factor VII for acute intracerebral hemorrhage: US phase IIA trial." ]	[ "Recombinant activated factor VII (factor VIIa) has prohaemostatic effects in bleeding patients with coagulation abnormalities. We aimed to test the hypothesis that recombinant factor VIIa could reduce perioperative blood loss in patients with normal coagulation systems. Therefore, we assessed safety and efficacy of this drug in patients undergoing retropubic prostatectomy, which is often associated with major blood loss and need for transfusion.\n In a double-blind, randomised placebo-controlled trial, we recorded blood loss and transfusion requirements in 36 patients undergoing retropubic prostatectomy, who were randomised to receive an intravenous bolus of recombinant factor VIIa (20 microg/kg or 40 microg/kg) or placebo in the early operative phase.\n Median perioperative blood loss was 1235 mL (IQR 1025-1407) and 1089 mL (928-1320) in groups given recombinant factor VIIa 20 microg/kg and 40 microg/kg, respectively, compared with 2688 mL (1707-3565) in the placebo group (p=0.001). Seven of twelve placebo-treated patients were transfused, whereas no patients who received 40 microg/kg recombinant factor VIIa needed transfusion. The odds ratio for receiving any blood product in patients treated with recombinant factor VIIa compared with control patients was 0 (95% CI 0.00-0.33) No adverse events arose.\n An injection of recombinant factor VIIa can reduce perioperative blood loss and eliminate the need for transfusion in patients undergoing major surgery.", "Coagulopathy caused by cirrhosis may contribute to excessive bleeding during hepatectomy. We evaluated the hemostatic effect and safety of recombinant factor VIIa (rFVIIa) in cirrhotic patients undergoing partial hepatectomy.\n Patients were randomized to rFVIIa 50 or 100 mug/kg or placebo, administered intravenously 10 minutes before surgery and every second hour during surgery. The primary efficacy end points were the proportion of patients receiving red blood cell (RBC) transfusions and the amount of RBCs transfused. The RBC transfusion trigger was blood loss of 500 mL. Safety end points included thromboembolic and adverse events.\n No statistically significant effect of rFVIIa treatment on efficacy end points was observed. Serious and thromboembolic adverse events occurred at similar incidences in the study groups.\n Using blood loss as a transfusion trigger, the efficacy of rFVIIa in reducing the requirement for RBC transfusion was not established in this study. No safety concerns were identified.", "Blood loss is a common complication of cardiac surgery. Evidence suggests that recombinant activated factor VII (rFVIIa) can decrease intractable bleeding in patients after cardiac surgery. Our objective was to investigate the safety and possible benefits of rFVIIa in patients who bleed after cardiac surgery.\n In this phase II dose-escalation study, patients who had undergone cardiac surgery and were bleeding were randomized to receive placebo (n=68), 40 microg/kg rFVIIa (n=35), or 80 microg/kg rFVIIa (n=69). The primary end points were the number of patients suffering critical serious adverse events. Secondary end points included rates of reoperation, amount of blood loss, and transfusion of allogeneic blood. There were more critical serious adverse events in the rFVIIa groups. These differences did not reach statistical significance (placebo, 7%; 40 microg/kg, 14%; P=0.25; 80 microg/kg, 12%; P=0.43). After randomization, significantly fewer patients in the rFVIIa group underwent a reoperation as a result of bleeding (P=0.03) or required allogeneic transfusions (P=0.01).\n On the basis of this preliminary evidence, rFVIIa may be beneficial for treating bleeding after cardiac surgery, but caution should be applied and further clinical trials are required because there is an increase in the number of critical serious adverse events, including stroke, in those patients randomized to receive rFVIIa.", "Orthotopic liver transplantation (OLT) is affected by important alterations of hemostasis. The aim of this study was to evaluate the efficacy of recombinant factor VII activated (rFVIIa) to reduce intraoperative bleeding during OLT.\n Twenty OLT patients were assigned in double-blind way to a rFVIIa group or a control group. Inclusion criteria were hemoglobin > 8 g/dL: INR > 1,5 and fibrinogen > 100 mg/dL. We administered a single bouls of rFVIIa (40 microg/kg) or placebo. We determined INR, partial thromboplastin time, fibrinogen, ATIII, and blood cell counts. Blood products were administered as follows: 4 units of fresh frozen plasma when INR > 1.5, and 1 unit of RBC for Hb < 10 g/dL. The study ended 6 hours after the bolus.\n No thromboembolic events occurred. The INR was different between rFVIIa group and the controls at T0 (1.9 vs 1.6 P < .021) and during T1 (1.2 vs 1.6 P < .004). The total transfused red blood cells was 300 mL +/- 133 in rFVIIa group and 570 mL +/- 111 in control group (P < .017). The total fresh frozen plasma was 600 mL +/- 154 in rFVIIa group and 1400 mL +/- 187 in control group (P < .001). Total blood loss was greater in the control group than the rFVIIa group: 1140 mL +/- 112 vs 740 mL +/- 131 (P < .049).\n The use of rFVIIa during OLT can reduce the risk of bleeding during surgery. The literature has described cases who did not benefit from the treatment. An adequate cut-off of INR, allowed us to treat only patients at greater bleeding risk.", "Patients undergoing orthotopic liver transplantation (OLT) have excessive blood loss during surgery that requires blood transfusions, leading to increased postoperative morbidity and mortality. We studied the efficacy and safety of activated recombinant factor VII (rFVIIa) in reducing transfusion requirements in OLT. This multicenter, randomized, double-blind, placebo-controlled trial enrolled patients undergoing OLT because of cirrhosis (Child-Turcotte-Pugh class B or C). Patients received a repeated intravenous bolus regimen of rFVIIa 60 or 120 microg/kg or placebo. The primary efficacy endpoint was the total number of red blood cell (RBC) units transfused during the perioperative period. A total of 182 patients were analyzed for efficacy and 183 for safety. No significant effect of rFVIIa was observed on the number of RBC units transfused or intraoperative blood loss compared with the placebo group. A significantly higher number of patients in the rFVIIa study groups avoided RBC transfusion. Administration of rFVIIa but not placebo restored the preoperative prolonged prothrombin time to normal value during surgery. Patients receiving rFVIIa and placebo did not experience a significant difference in rate of thromboembolic events. Additionally, there was no statistically significant effect of rFVIIa treatment on hospitalization rate, total surgery time, and the proportion of patients undergoing retransplantation. In conclusion, use of rFVIIa during OLT significantly reduced the number of patients requiring RBC transfusion. There was no increase in thromboembolic events with rFVIIa administration compared with placebo.", "Prevention of bleeding episodes in noncirrhotic patients undergoing partial hepatectomy remains unsatisfactory in spite of improved surgical techniques. The authors conducted a randomized, placebo-controlled, double-blind trial to evaluate the hemostatic effect and safety of recombinant factor VIIa (rFVIIa) in major partial hepatectomy.\n Two hundred four noncirrhotic patients were equally randomized to receive either 20 or 80 microg/kg rFVIIa or placebo. Partial hepatectomy was performed according to local practice at the participating centers. Patients were monitored for 7 days after surgery. Key efficacy parameters were perioperative erythrocyte requirements (using hematocrit as the transfusion trigger) and blood loss. Safety assessments included monitoring of coagulation-related parameters and Doppler examination of hepatic vessels and lower extremities.\n The proportion of patients who required perioperative red blood cell transfusion (the primary endpoint) was 37% (23 of 63) in the placebo group, 41% (26 of 63) in the 20-microg/kg group, and 25% (15 of 59) in the 80-microg/kg dose group (logistic regression model; P = 0.09). Mean erythrocyte requirements for patients receiving erythrocytes were 1,024 ml with placebo, 1,354 ml with 20 microg/kg rFVIIa, and 1,036 ml with 80 microg/kg rFVIIa (P = 0.78). Mean intraoperative blood loss was 1,422 ml with placebo, 1,372 ml with 20 microg/kg rFVIIa, and 1,073 ml with 80 microg/kg rFVIIa (P = 0.07). The reduction in hematocrit during surgery was smallest in the 80-microg/kg group, with a significant overall effect of treatment (P = 0.04).\n Recombinant factor VIIa dosing did not result in a statistically significant reduction in either the number of patients transfused or the volume of blood products administered. No safety issues were identified.", "Excision of burn wounds is frequently associated with a large volume of blood loss requiring allogeneic blood transfusion. We conducted a pilot study to investigate the effect of activated recombinant coagulation factor VII (rFVIIa) on the reduction of blood transfusion requirements in burn patients undergoing excision and skin grafting.\n Eighteen consecutive patients scheduled for the surgery were randomised to receive either placebo or 40 microg/kg rFVIIa administered at first skin incision, and a second dose (40 microg/kg) at 90 min later. Blood transfusion requirements during, and up to 24h post-surgery per patient and percentage full thickness wound excised were compared. In addition, postoperative complications commonly seen in patients with burns as well as adverse events related to rFVIIa were monitored.\n rFVIIa significantly decreased the total number of units of blood components transfused per patient and percentage full thickness burn wound excised compared with placebo (0.9 versus 2.2, p=0.0013) including significant fewer red blood cell units (0.5 versus 1.1, p=0.004). We further observed a trend towards improved graft survival (p=0.1) and a reduction in multiple organ failures (p=0.08) in the rFVIIa-treated group. There were no adverse events, in particular thromboembolic events.\n rFVIIa might be useful in decreasing blood transfusion requirements in burn patients undergoing excision and skin grafting.", "Uncontrolled bleeding is a leading cause of death in trauma. Two randomized, placebo-controlled, double-blind trials (one in blunt trauma and one in penetrating trauma) were conducted simultaneously to evaluate the efficacy and safety of recombinant factor VIIa (rFVIIa) as adjunctive therapy for control of bleeding in patients with severe blunt or penetrating trauma.\n Severely bleeding trauma patients were randomized to rFVIIa (200, 100, and 100 microg/kg) or placebo in addition to standard treatment. The first dose followed transfusion of the eighth red blood cell (RBC) unit, with additional doses 1 and 3 hours later. The primary endpoint for bleeding control in patients alive at 48 hours was units of RBCs transfused within 48 hours of the first dose.\n Among 301 patients randomized, 143 blunt trauma patients and 134 penetrating trauma patients were eligible for analysis. In blunt trauma, RBC transfusion was significantly reduced with rFVIIa relative to placebo (estimated reduction of 2.6 RBC units, p = 0.02), and the need for massive transfusion (>20 units of RBCs) was reduced (14% vs. 33% of patients; p = 0.03). In penetrating trauma, similar analyses showed trends toward rFVIIa reducing RBC transfusion (estimated reduction of 1.0 RBC units, p = 0.10) and massive transfusion (7% vs. 19%; p = 0.08). Trends toward a reduction in mortality and critical complications were observed. Adverse events including thromboembolic events were evenly distributed between treatment groups.\n Recombinant FVIIa resulted in a significant reduction in RBC transfusion in severe blunt trauma. Similar trends were observed in penetrating trauma. The safety of rFVIIa was established in these trauma populations within the investigated dose range.", "Randomized, placebo-controlled, double-blind, multicenter, Phase IIa study.\n To assess the safety and efficacy of recombinant-activated Factor VII (rFVIIa) in major spinal surgery.\n Spinal fusion surgery can cause substantial blood loss and blood product transfusions. Recombinant FVIIa is approved for treatment of bleeding in patients with coagulation abnormalities and has been shown to reduce blood loss and transfusion requirements in surgery in patients with no underlying coagulopathy.\n Forty-nine patients undergoing fusion of 3 or more vertebral segments were randomized and treated on losing 10% of their estimated blood volume (with total expected surgical blood loss > or = 20%) and received 3 doses (2-hour intervals) of placebo (n = 13) or 30, 60, or 120 microg/kg rFVIIa (n = 12 per group). The primary endpoint was safety. A priori-defined efficacy endpoints included blood loss and transfusion requirements between placebo and each rFVIIa dose group, adjusted for surgery duration, number of segments fused, and estimated blood volume.\n Serious adverse events did not occur at any greater frequency in any of the treatment groups. One patient (3 x 30 microg/kg rFVIIa) with advanced cerebrovascular disease (undiagnosed, trial exclusion criterion) died 6 days after surgery due to an ischemic stroke. Mean blood loss was as follows: 2270 mL for placebo; 1909, 1262, and 1868 mL for 3 x 30, 3 x 60, and 3 x 120 microg/kg rFVIIa, respectively (differences not statistically significant). Mean adjusted surgical blood loss was as follows: 2536 mL for placebo; 1120, 400, and 823 mL for 3 x 30, 3 x 60, and 3 x 120 microg/kg rFVIIa, respectively (P < or = 0.001). Mean surgical transfusion volume was reduced by 27% to 50% with rFVIIa treatment (not significant). The mean adjusted surgical transfusion volume was reduced by 81% to 95% with rFVIIa treatment (P < or = 0.002).\n No safety concerns were indicated for the use of rFVIIa in patients at all doses tested; rFVIIa reduced adjusted blood loss and adjusted transfusions during spinal surgery.", "Orthotopic liver transplantation (OLT) can be associated with excessive blood loss. As a result, there may be increased risk of adverse outcomes. Activated recombinant factor VII (rFVIIa) has demonstrated the ability to improve hemostasis in a variety of disorders; however, there has been a limited amount of research into its use in OLT. The purpose of this dose-finding study was to examine the efficacy and safety of rFVIIa in the reduction of bleeding in patients undergoing OLT. In this double-blind trial, patients with end-stage liver disease scheduled for OLT were randomized to 1 of 4 parallel study groups. They received a single intravenous bolus of rFVIIa (20, 40, or 80 microg/kg) or placebo prior to surgery. The primary assessment endpoint was the total number of red blood cell (RBC) units transfused perioperatively. Safety was evaluated by adverse events reported. Eighty-three comparable patients were randomized to receive study product, with 82 ultimately undergoing OLT. There were no significant differences in required RBC units between the placebo and rFVIIa study groups. The number of adverse events was comparable between study groups. In conclusion, rFVIIa has a good safety profile in patients undergoing OLT. However, the doses studied did not have any effect on the number of RBC transfusions required.", "Traumatic coagulopathy contributes to early death by exsanguination and late death in multiple organ failure. Recombinant Factor VIIa (rFVIIa, NovoSeven) is a procoagulant that might limit bleeding and improve trauma outcomes.\n We performed a phase 3 randomized clinical trial evaluating efficacy and safety of rFVIIa as an adjunct to direct hemostasis in major trauma. We studied 573 patients (481 blunt and 92 penetrating) who bled 4 to 8 red blood cell (RBC) units within 12 hours of injury and were still bleeding despite strict damage control resuscitation and operative management. Patients were assigned to rFVIIa (200 μg/kg initially; 100 μg/kg at 1 hour and 3 hours) or placebo. Intensive care unit management was standardized using evidence-based trauma \"bundles\" with formal oversight of compliance. Primary outcome was 30-day mortality. Predefined secondary outcomes included blood products used. Safety was assessed through 90 days. Study powering was based on prior randomized controlled trials and large trauma center databases.\n Enrollment was terminated at 573 of 1502 planned patients because of unexpected low mortality prompted by futility analysis (10.8% vs. 27.5% planned/predicted) and difficulties consenting and enrolling sicker patients. Mortality was 11.0% (rFVIIa) versus 10.7% (placebo) (p = 0.93, blunt) and 18.2% (rFVIIa) versus 13.2% (placebo) (p = 0.40, penetrating). Blunt trauma rFVIIa patients received (mean ± SD) 7.8 ± 10.6 RBC units and 19.0 ± 27.1 total allogeneic units through 48 hours, and placebo patients received 9.1 ± 11.3 RBC units (p = 0.04) and 23.5 ± 28.0 total allogeneic units (p = 0.04). Thrombotic adverse events were similar across study cohorts.\n rFVIIa reduced blood product use but did not affect mortality compared with placebo. Modern evidence-based trauma lowers mortality, paradoxically making outcomes studies increasingly difficult.", "Activated recombinant coagulation factor VII (rFVIIa) effectively prevents and controls bleeding in patients with coagulopathy. Data show that rFVIIa may reduce blood loss and eliminate the need for transfusion in patients with normal haemostasis undergoing major surgery. We assessed the efficacy of rFVIIa in patients with normal haemostasis undergoing repair surgery of major traumatic fracture of the pelvis or the pelvis and acetabulum, who were expected to have a large volume of blood loss.\n We performed a double-blind, randomized, placebo-controlled trial involving 48 patients undergoing major pelvic-acetabular surgery. Patients were randomized to receive an i.v. bolus injection of rFVIIa 90 microg kg(-1) or placebo as add-on therapy at the time of the first skin incision. All patients also received intraoperative salvaged red blood cells (RBC).\n There was no significant difference in the total volume of perioperative blood loss, the primary outcome variable, between the rFVIIa and placebo groups. In addition, there were no differences between the two groups in the total volume of blood components, including salvaged RBC transfused, number of patients requiring allogeneic blood components, total volume of fluids infused, total operating time, time taken after entry to the intensive care unit to reach normal body temperature and acid-base status, and time spent in hospital. No adverse events, in particular thromboembolic events, were reported in either group.\n In patients with normal haemostasis undergoing repair surgery of traumatic pelvic-acetabular fracture, the prophylactic use of rFVIIa does not decrease the volume of perioperative blood loss.", "Aprotinin reduces blood loss in many orthopedic procedures. In posterior lumbar spine fusion, blood loss results primarily from large vein bleeding and also occurs after the wound is closed. Seventy-two patients undergoing posterior lumbar spine fusion were randomly assigned to large-dose aprotinin therapy or placebo. All patients donated three units of packed red blood cells (RBCs) preoperatively. Postoperative blood loss was harvested from the surgical wound in patients undergoing two- and/or three-level fusion for reinfusion. The target hematocrit for RBC transfusion was 26% if tolerated. Total (intraoperative and 24 h postoperative) blood loss, transfusion requirements, and percentage of transfused patients per treatment group were significantly smaller in the aprotinin group than in the placebo group (1935 +/- 873 vs 2809 +/- 973 mL per patient [P = 0.007]; 42 vs 95 packed RBCs per group [P = 0.001]; 40% vs 81% per group [P = 0.02]). Hematological assessments showed an identically significant (a) intraoperative increase in both thrombin-antithrombin III complexes (TAT) and in activated factor XII (XIIa) and (b) decrease in activated factor VII (VIIa), indicating a similar significant effect on coagulation in patients of both groups (P = 0.9 for intergroup comparisons of postoperative VIIa, XIIa, and TAT). Intraoperative activation of fibrinolysis was significantly less pronounced in the aprotinin group than in the placebo group (P < 0.0001 for intergroup comparison of postoperative D-dimer levels). No adverse drug effects (circulatory disturbances, deep venous thrombosis, alteration of serum creatinine) were detected. Although administered intraoperatively, aprotinin treatment dramatically reduced intraoperative and 24-h postoperative blood loss and autologous transfusion requirements but did not change homologous transfusion in posterior lumbar spine fusion.\n In our study, aprotinin therapy significantly decreased autologous, but not homologous, transfusion requirements in posterior lumbar spine fusion.", "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.", "Major orthopedic surgery can be associated with dramatic blood loss, thereby requiring high-volume homologous transfusions in patients unable to benefit from blood salvage techniques. The effect of aprotinin on blood loss and transfusion requirements during orthopedic surgery for either the resection of malignancies of the removal of infected hardware was prospectively studied.\n Twenty-three patients scheduled for orthopedic surgery of the hip, femur, or pelvis for sepsis or malignant tumors, all under general anesthesia, were randomly allocated to receive during operation, in a blinded manner, either aprotinin administered as a bolus of 1.106 kallikrein inactivation units (KIU) followed by an infusion of 5 x 10(5) KIU/h, or the equivalent volume of saline. The anesthesia and perioperative management, as well as the designated transfusion criteria, were standardized. The total blood loss of each patient was evaluated using intraoperative suction losses, sponge weights, and postoperative volumetric drainage. Homologous transfusion requirements were noted. Hemoglobin and hematocrit measures, as well as coagulation and fibrinolytic pathway explorations, were performed before and after surgery. Deep venous thrombosis prophylaxis was applied, and the incidence of this complication was assessed.\n Twelve patients received aprotinin. Aprotinin reduced the total blood loss from a median of 5,305 ml (range, 3,000-9,770 ml) to a median of 1,783 ml (range, 1,140-4,955 ml; P < 0.05). A blood loss reduction of 56% during surgery and 68% on discharge from the postanesthesia care unit was observed. Seven units (range, 4-16) of packed erythrocytes were transfused per patient in the placebo group, and 3 (range, 2-5) were transfused in the aprotinin group (P < 0.05). In the aprotinin group, platelet counts were higher, and postoperative prothrombin times and D. Dimer values were lower. The activated partial thromboplastin time values showed no significant difference between the two groups. No side effects were observed in the aprotinin group. A deep venous thrombosis developed in one patient in the placebo group.\n Aprotinin treatment during major orthopedic surgery significantly reduces both blood loss and consequent homologous blood transfusion requirements.", "Controlled study to assess the efficacy of aprotinin and Amicar in reducing blood loss during complex spinal fusions.\n To compare blood loss and the clotting profile with a thromboelastogram in patients with spinal deformities undergoing sequential anterior and posterior spinal fusions treated intraoperatively with either aprotinin or Amicar.\n Spinal fusion for correction of adult spinal deformities is associated with large blood losses despite the implementation of multiple factors to reduce this blood loss. The antifibrinolytics aprotinin and Amicar have both been shown to reduce blood loss in other surgical procedures with the potential for large blood loss. Hence, we compared their efficacy for reducing blood loss in complex spinal fusions.\n Sixty patients for elective sequential anteroposterior thoracolumbosacral fusions were randomly assigned to three groups: control, aprotinin, and Amicar. Patients were assessed for blood loss, transfusion requirements, postoperative complications, and coagulation profile using a thromboelastogram.\n The study demonstrated a significant reduction in total blood loss (aprotinin 3628 mL, Amicar 4056 mL, control 5181 mL) and transfusion requirements using the half-dose aprotinin regimen compared with Amicar or control. Aprotinin also preserved the thromboelastogram mean clot formation time, clot strength, and clotting index compared with Amicar or control.\n For complex spinal operations with large blood losses, the half-dose aprotinin regimen will reduce blood loss and the need for blood components and may have a role in reducing postoperative lung injury.", "We investigated the effectiveness of prophylactic administration of recombinant activated factor VII (rFVIIa) for cardiopulmonary bypass surgery in children under 1 year old with congenital heart disease (CHD) in a double-blinded, placebo-controlled study. The rFVIIa dose was 40 microg/kg and all patients also received standard haemostatic replacement therapy. The primary endpoint was the time to chest closure from neutralization of heparin with protamine sulphate as this could be most objectively and accurately measured during surgery. Secondary endpoints were volumes of transfused blood, platelet concentrates and fresh-frozen plasma. All adverse events were recorded. In the intention-to-treat analysis there were 76 patients (40 in rFVIIa group and 36 in placebo group). The demographics and severity of CHD were similar in both groups. No benefit of rFVIIa prophylaxis was found in the time to chest closure, which was significantly prolonged in the rFVIIa group (rFVIIa mean +/- SE, 98.8 +/- 27.27 versus 55.3 +/- 29.15, P = 0.0263). In the 41 patients available for a follow-up visit 6 weeks after discharge, the chest closure time was also prolonged in the rFVIIa group (P = 0.0515). There were no significant differences in the secondary endpoints. Adverse events were similar in both groups.", "Acute preoperative plateletpheresis (APP), cell salvage (CS) technique, and the use of aprotinin have been individually reported to be effective in reducing blood loss and blood component transfusion while improving hematological profiles in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). In this prospective randomized clinical study, the efficacy of these combined approaches on reducing blood loss and transfusion requirements was evaluated. Seventy patients undergoing primary coronary artery bypass grafting (CABG) were randomly divided into four groups: a control group (group I, n = 10) did not receive any of the previously mentioned approaches. An APP and CS group (group II, n = 20) experienced APP in which preoperative platelet-rich plasma was collected and reinfused after reversal of heparin, along with the cell salvage technique throughout surgery. The third group (group III, n = 22) received aprotinin in which 5,000,000 KIU Trasylol was applied during surgery, and a combination group (group IV, n = 18) was treated with all three approaches, i.e., APP, CS, and aprotinin. Compared with group I (896+/-278 mL), the postoperative total blood loss was significantly reduced in groups II, III, and IV (468+/-136, 388+/-122, 202+/-81 mL, respectively, p < 0.05). The requirements of packed red blood cells in the three approached groups (153+/-63, 105+/-178, 0+/-0 mL, respectively) also were reduced when compared with group I (343+/-118 mL, p < 0.05). In group I, six patients (6/10) received fresh-frozen plasma and three patients (3/10) received platelet transfusion, whereas no patients in the other three groups required fresh-frozen plasma and platelet. In conclusion, both plateletpheresis concomitant with cell salvage and aprotinin contribute to the improvement of postoperative hemostasis, and the combination of these two approaches could minimize postoperative blood loss and requirement.", "To evaluate the efficacy of a 2 million KIU single dose of aprotinin on blood loss, transfusion requirements, and incidence of deep venous thrombosis (DVT) in patients undergoing total hip replacement surgery.\n Randomized study.\n Operating theater at an orthopedic hospital.\n 40 adult patients scheduled for total hip replacement surgery.\n Patients were randomized to two groups. Group A (n = 20) received 2 million KIU of aprotinin over 20 minutes, Group C (n = 20), the control group, received placebo. Anesthesia and surgical technique were standardized. MEASUREMENTS AND MAIN-RESULTS: Intraoperative blood loss, postoperative blood loss, transfusion requirements (48 hr), hemoglobin, coagulation parameters, and platelet counts were assessed. On the seventh postoperative day, all patients in both groups underwent venography to ascertain the incidence of DVT. We found no significant difference in blood loss or transfusion requirements between the two groups. Intraoperative and postoperative blood losses, coagulation parameters, and incidence of DVT did not differ significantly between the two groups.\n A single 2 million KIU bolus dose of aprotinin does not reduce perioperative blood loss or transfusion requirements. Aprotinin therapy, when used in conjunction with other antithrombotic therapies, does not increase the incidence of DVT after major orthopedic surgery.", "Bleeding and allogeneic transfusion remain constant problems in cardiac surgical procedures. In this study, we aimed to test the role of a routine thromboelastography (TEG)-based algorithm on bleeding and transfusions in patients undergoing elective coronary artery bypass grafting (CABG).\n Patients (n = 224) undergoing elective CABG with cardiopulmonary bypass were prospectively randomized into two groups according to transfusion strategy: in group 1 (clinician-directed transfusion, n = 110) need for blood transfusion was based on clinician's discretion and standard coagulation tests and in group 2 (TEG algorithm group, n = 114) kaolin-activated (k) TEG-based algorithm-guided perioperative transfusion management. Transfusion, blood loss, and outcome data were recorded.\n There were no differences in consumption of packed cell units, blood loss, re-exploration for bleeding, and early clinical outcome between the groups. Patients in the TEG group had significantly lower median units of fresh frozen plasma and platelets compared with the other group (p = 0.001). The median number of total allogeneic units transfused (packed cells and blood products) was significantly reduced in the TEG group compared with the other group (median 2, range 1-3 units vs. median 3, range 2-4 units, respectively, p = 0.001). The need for tranexamic acid was significantly diminished in the TEG group compared with the other group (10.3% vs. 19%, respectively, p = 0.007).\n Our results show that routine use of a kTEG-guided algorithm reduces the consumption of blood products in patients undergoing elective CABG. Adopting such an algorithm into routine management of these patients may help to improve clinical outcome and reduce the potential risks of transfusion-related complications and total costs after CABG.", "Ninety-seven patients undergoing elective liver resection through a subcostal incision were assigned to large-dose aprotinin treatment or placebo in a double-blind, prospective, randomized fashion. Randomization was stratified by diagnosis: (a) cancer in cirrhosis, (b) cancer in healthy liver, and (c) benign tumor in healthy liver. Intraoperative blood loss, percentage of transfused patients, and total transfusion requirement per group were significantly lower in the aprotinin group than in the placebo group (1217 +/- 966 mL vs 1653 +/- 1221 mL, P = 0.048; 17% vs 39%, P = 0.02; 30 vs 77 red blood cell packs, P = 0.015, respectively). Assessment of hematological markers (a) prior to surgery, (b) at the end of surgery, and (c) 24 h after surgery showed an identical intraoperative increase in thrombin-antithrombin III complexes in patients of both groups (P = 0.86), which indicates a similar activation of coagulation. Intraoperative hyperfibrinolysis was significantly less pronounced in the aprotinin group than in the placebo group (P = 0.0002 and P = 0.004 for D-dimers and fibrinogen, respectively). No adverse drug effects were detected (circulatory disturbances, deep venous thrombosis, increase in serum creatinine). These results suggest that aprotinin significantly reduces blood loss and transfusion requirement in patients undergoing elective liver resection through a subcostal incision.", "Ninety patients undergoing cardiac surgery were randomly divided into three groups of 30 patients to compare the effects on bleeding and transfusion requirements of either intraoperative infusion of high-dose aprotinin (GpI) or reinfusion of autologous fresh whole blood (GpII) versus a control group (GpIII). Standardized anesthetic, perfusion, and surgical techniques were used. Platelet counts, hemoglobin concentration, hematocrit, fibrinogen, and Ivy-Nelson bleeding times determined at fixed times perioperatively did not differ among the three groups. The total loss from the chest drains was significantly reduced in GpI (328 +/- 28 mL; mean +/- SEM) as compared with the loss in GpII and GpIII (775 +/- 75 mL and 834 +/- 68 mL, respectively). There was a threefold difference in the total hemoglobin loss (GpI, 14.2 +/- 1.7 g; GpII, 50.1 +/- 5.0 g; GpIII, 45.0 +/- 5.2 g). GpI patients also received less banked blood: 250 +/- 53 mL versus 507 +/- 95 mL in GpII and 557 +/- 75 mL in GpIII. No GpI patient required transfusion of platelets or fresh frozen plasma. Fresh whole autologous blood transfusions had no significant hemostatic effect and failed to reduce the homologous blood requirement. Conversely, high-dose aprotinin reduced blood loss and transfusion requirements.", "The serine protease antagonist, aprotinin, reduces perioperative blood loss in cardiac surgery and orthotopic liver transplantation. A pilot study suggested that the drug may also reduce bleeding during infrarenal aortic replacement; the aim was to confirm or refute this observation with a prospective, randomized, double-blind, placebo-controlled trial.\n Some 136 patients were randomized to receive either aprotinin, given as a loading dose of 2 x 10(6) kallikrein inactivator (KI) units followed by 0.5 x 10(6) KI units/h or equal volumes of 0.9 per cent saline. After 80 patients had been randomized the infusion dose was doubled to ensure that plasma levels were similar to those seen in successful cardiac studies. Blood loss, coagulation and haematological parameters were recorded throughout surgery and for 7 days afterwards. Blood was transfused to maintain the haemoglobin level at 100 g/l.\n Four patients were withdrawn after randomization when found at laparotomy to be unsuitable for the planned reconstruction. The 30-day mortality rate was 4.5 per cent, with no excess complications in either group. Blood loss collected on swabs was reduced from 480 ml in placebo-treated patients to 379 ml with aprotinin (P = 0.014). Blood loss into suction drains in the first 24 h after operation was reduced from 295 to 205 ml in aprotinin-treated patients (P = 0.002). However, no significant reduction was found in intraoperative or total blood loss, or transfusion requirement.\n The small reduction in blood loss in patients treated with aprotinin demonstrated in this study does not support its use in routine elective aortic surgery.", "Anemia may be an important factor contributing to an increased risk of bleeding, particularly in patients with thrombocytopenia.\n A multicenter, single-blinded pilot randomized controlled trial (RCT) was performed to evaluate the feasibility of conducting a larger RCT to determine the effect of the hemoglobin (Hb) concentration on bleeding risk. Patients with acute leukemia receiving induction chemotherapy or those undergoing stem cell transplantation were assigned to one of two treatment groups: standard transfusion strategy (transfusion of 2 units of red blood cells [RBCs] when their Hb level was less than 80 g/L) or an augmented transfusion strategy (transfusion of 2 units of RBCs when their Hb level was less than 120 g/L).\n Sixty patients were enrolled: 29 in the control group and 31 in the experimental group. The proportions of patients experiencing clinically significant bleeding and the time to first bleed were not significantly different between the control and experimental groups. The experimental group received more RBC transfusions (transfusions/patient-day) than the control group (0.233 vs. 0.151; relative risk, 1.56; 95% confidence interval, 1.16-2.10; p = 0.003). The proportion of patient-days with platelet (PLT) transfusions was not different between the experimental and control groups. The mean number of donor exposures (PLT and RBC transfusions) was not different between experimental and control groups. Bleeding symptoms were systematically documented.\n This pilot study thus indicated that it would be feasible to enroll the required number of patients to enable the performance of a large RCT to investigate the effect of Hb on bleeding risk in thrombocytopenic patients.", "80 patients underwent total hip replacement (THR) for primary coxarthrosis. In a randomized study, half of them donated 2 units of blood before operation. One unit was collected 4 weeks and one 2 weeks before the scheduled THR. All except 1 patient tolerated the predonations well. Total blood losses were similar in both groups. Additional bank blood was given in 7/38 in the predonation group, compared to 29/40 in the control group. Hemostatic parameters were studied in 10 consecutive patients in each group. Plasminogen activator inhibitor 1 (PAI-1), a possible risk parameter for thromboembolism, was significantly more increased postoperatively in the control group, which received only homologous blood. Platelet count, prothrombin complex, antithrombin III and von Willebrand factor antigen were significantly reduced and C reactive protein increased after surgery in both groups. We recommend predonation of 2 autologous units before a primary THR. In most cases, such predonation makes homologous blood transfusion unnecessary. The use of predonated blood causes no reduction of blood loss in THRs, but the increase in PAI-1 seen after homologous transfusions is avoided.", "Ultra-early hemostatic therapy may improve outcome after intracerebral hemorrhage (ICH) by preventing rebleeding and hematoma expansion. We conducted this trial to evaluate the safety of activated recombinant factor VII (rFVIIa; NovoSeven) for preventing early hematoma growth in acute ICH.\n In this multicenter, randomized, double-blind, placebo-controlled, dose-escalation trial, 40 patients diagnosed with ICH by computed tomography within 3 hours of onset were treated with placebo or 5, 20, 40, or 80 microg/kg of rFVIIa ( n = 8 per group). Patients with any history of thromboembolic or vaso-occlusive disease were excluded. The primary endpoint was the frequency of adverse events (AEs).\n Mean age was 65 years (range 34 - 91) and the median admission Glasgow Coma Scale score was 14.5 (range 6 to 15). Mean ICH volume was 17 +/- 19 mL; nearly three-quarters were located in the basal ganglia ( n = 29). The mean interval from onset to treatment was 178 +/- 41 minutes. Thirty-three patients experienced 186 AEs, which occurred with similar frequency in the five groups. There were 10 thromboembolic AEs, including one case of deep vein thrombosis (20 microg g/kg group); one case of cerebral infarction (placebo); two cases of pulmonary embolism (20 and 40 microg g/kg groups); and six instances of ischemic ECG changes or cardiac enzyme elevation (placebo [ n = 2], 20 microg g/kg [ n = 1], 40 microg g/kg [ n = 1], and 80 microg g/kg [ n = 2] groups). No consumption coagulopathy or dose-related increase in edema-to-ICH volume ratio occurred.\n Ultra-early rFVIIa treatment for ICH was associated with a reasonable safety profile in this preliminary study across a wide range of dosages. Further research is warranted to investigate the safety and potential efficacy of rFVIIa for minimizing ICH growth." ]	Aprotinin, recombinant factor VIIa, and thromboelastography groups may potentially reduce blood loss and transfusion requirements. However, risks of systematic errors (bias) and risks of random errors (play of chance) hamper the confidence in this conclusion. We need further well-designed randomised trials with low risk of systematic error and low risk of random errors before these interventions can be supported or refuted.
CD007722	[ "2223679" ]	[ "Idiopathic thrombocytopenic purpura in pregnancy: a randomized trial on the effect of antenatal low dose corticosteroids on neonatal platelet count." ]	[ "To determine the efficacy of antenatal low dose oral betamethasone in preventing neonatal thrombocytopenia and/or bleeding in infants of mothers with idiopathic thrombocytopenic purpura (ITP).\n Hospital department of obstetrics and gynaecology, referral centre.\n 41 pregnancies in 38 women were randomized. The results of 13 pregnancies were considered non-assessable. The final analysis involved 14 in the betamethasone group and 14 in the non-treatment group. All fulfilled the criteria for ITP.\n The treated group received 1.5 mg betamethasone orally per day, from day 259 till day 273 and 1 mg from day 273 till delivery.\n Effects of treatment were assessed in terms of maternal platelet counts after the first trimester and neonatal platelet counts at birth and the first week of life and neonatal bleeding episodes.\n There were no significant differences in neonatal platelet counts at birth. Two infants in the betamethasone group and one in the untreated group had a severe thrombocytopenia either at birth or during the first week of life (less than 50 x 10(9)/l). Seven infants in the betamethasone group and six in the non-treatment group had a mild thrombocytopenia. The overall frequency of neonatal thrombocytopenia was similar: 64% in the betamethasone group and 57% in the untreated group (95% CI of the true difference: -43.5% to +29.5%). There was also no significant difference in neonatal bleeding episodes.\n Low-dose betamethasone in pregnant women with ITP does not prevent thrombocytopenia or bleeding in their newborn infants." ]	Current evidence indicates that compared to no medication, betamethasone did not reduce the risk of neonatal thrombocytopenia and neonatal bleeding in ITP during pregnancy. There is insufficient evidence to support the use of betamethasone for treating ITP. This Cohrane review does not provide evidence about other medical treatments for ITP during pregnancy. This systematic review also identifies the need for well-designed, adequately powered randomised clinical trials for this medical condition during pregnancy. Unless randomised clinical trials provide evidence of a treatment effect and the trade off between potential benefits and harms are established, policy-makers, clinicians, and academics should not use betamethasone for ITP in pregnant women. Any future trials on medical treatments for treating ITP during pregnancy should test a variety of important maternal, neonatal or both outcome measures, including maternal death, perinatal mortality, postpartum haemorrhage and neonatal intracranial haemorrhage.
CD006491	[ "11528574", "10348224", "14604928", "12235450", "12471569", "11493411", "11130385" ]	[ "Atovaquone-proguanil versus mefloquine for malaria prophylaxis in nonimmune travelers: results from a randomized, double-blind study.", "Efficacy and safety of atovaquone/proguanil compared with mefloquine for treatment of acute Plasmodium falciparum malaria in Thailand.", "Tolerability of malaria chemoprophylaxis in non-immune travellers to sub-Saharan Africa: multicentre, randomised, double blind, four arm study.", "Atovaquone plus chloroguanide versus mefloquine for malaria prophylaxis: a focus on neuropsychiatric adverse events.", "Treatment of uncomplicated multidrug-resistant falciparum malaria with artesunate-atovaquone-proguanil.", "Atovaquone and proguani hydrochloride compared with chloroquine or pyrimethamine/sulfodaxine for treatment of acute Plasmodium falciparum malaria in Peru.", "Atovaquone-proguanil versus chloroquine-proguanil for malaria prophylaxis in non-immune travellers: a randomised, double-blind study. Malarone International Study Team." ]	[ "Concerns about the tolerability of mefloquine highlight the need for new drugs to prevent malaria. Atovaquone-proguanil (Malarone; GlaxoSmithKline) was safe and effective for prevention of falciparum malaria in lifelong residents of malaria-endemic countries, but experience in nonimmune people is limited. In a randomized, double-blind study, nonimmune travelers received malaria prophylaxis with atovaquone-proguanil (493 subjects) or mefloquine (483 subjects). Information about adverse events (AEs) and potential episodes of malaria was obtained 7, 28, and 60 days after travel. AEs were reported by an equivalent proportion of subjects who had received atovaquone-proguanil or mefloquine (71.4% versus 67.3%; difference, 4.1%; 95% confidence interval, -1.71 to 9.9). Subjects who received atovaquone-proguanil had fewer treatment-related neuropsychiatric AEs (14% versus 29%; P=.001), fewer AEs of moderate or severe intensity (10% versus 19%; P=.001), and fewer AEs that caused prophylaxis to be discontinued (1.2% versus 5.0%; P=.001), compared with subjects who received melfoquine. No confirmed diagnoses of malaria occurred in either group. Atovaquone-proguanil was better tolerated than was mefloquine, and it was similarly effective for malaria prophylaxis in nonimmune travelers.", "The increasing frequency of therapeutic failures in falciparum malaria underscores the need for novel, rapidly effective antimalarial drugs or drug combinations. Atovaquone and proguanil are blood schizonticides that demonstrate synergistic activity against multi-drug-resistant Plasmodium falciparum in vitro. In an open-label, randomized, controlled clinical trial conducted in Thailand, adult patients with acute P. falciparum malaria were randomly assigned to treatment with atovaquone and proguanil/hydrochloride (1,000 mg and 400 mg, respectively, administered orally at 24-hr intervals for three doses) or mefloquine (750 mg administered orally, followed 6 hr later by an additional 500-mg dose). Efficacy was assessed by cure rate (the percentage of patients in whom parasitemia was eliminated and did not recur during 28 days of follow-up), parasite clearance time (PCT), and fever clearance time (FCT). Safety was assessed by sequential clinical and laboratory assessments for 28 days. Atovaquone/proguanil was significantly more effective than mefloquine (cure rate 100% [79 of 79] vs. 86% [68 of 79]; P < 0.002). The atovaquone/proguanil and mefloquine treatments did not differ with respect to PCT (mean = 65 hr versus 74 hr) or FCT (mean = 59 hr versus 51 hr). Adverse events were generally typical of malaria symptoms and each occurred in < 10% of the patients in either group, with the exception of increased vomiting found in the atovaquone/proguanil group. Transient elevations of liver enzyme levels occurred more frequently in patients treated with atovaquone/proguanil than with mefloquine, but the differences were not significant and values returned to normal by day 28 in most patients. The combination of atovaquone and proguanil was well tolerated and more effective than mefloquine in the treatment of acute uncomplicated multidrug-resistant falciparum malaria in Thailand.", "To compare the tolerability of malaria chemoprophylaxis regimens in non-immune travellers.\n Randomised, double blind, study with placebo run-in phase.\n Travel clinics in Switzerland, Germany, and Israel.\n Proportion of participants in each treatment arm with subjectively moderate or severe adverse events.\n 623 non-immune travellers to sub-Saharan Africa: 153 each received either doxycycline, mefloquine, or the fixed combination chloroquine and proguanil, and 164 received the fixed combination atovaquone and proguanil.\n A high proportion of patients reported adverse events, even in the initial placebo group. No events were serious. The chloroquine and proguanil arm had the highest proportion of mild to moderate adverse events (69/153; 45%, 95% confidence interval 37% to 53%), followed by mefloquine (64/153; 42%, 34% to 50%), doxycycline (51/153; 33%, 26% to 41%), and atovaquone and proguanil (53/164; 32%, 25% to 40%) (P = 0.048 for all). The mefloquine and combined chloroquine and proguanil arms had the highest proportion of more severe events (n = 19; 12%, 7% to 18% and n = 16; 11%, 6% to 15%, respectively), whereas the combined atovaquone and proguanil and doxycycline arms had the lowest (n = 11; 7%, 2% to 11% and n = 9; 6%, 2% to 10%, respectively: P = 0.137 for all). The mefloquine arm had the highest proportion of moderate to severe neuropsychological adverse events, particularly in women (n = 56; 37%, 29% to 44% versus chloroquine and proguanil, n = 46; 30%, 23% to 37%; doxycycline, n = 36; 24%, 17% to 30%; and atovaquone and proguanil, n = 32; 20%, 13% to 26%: P = 0.003 for all). The highest proportion of moderate or severe skin problems were reported in the chloroquine and proguanil arm (n = 12; 8%, 4% to 13% versus doxycycline, n = 5; 3%, 1% to 6%; atovaquone and proguanil, n = 4; 2%, 0% to 5%; mefloquine, n = 2; 1%, 0% to 3%: P = 0.013).\n Combined atovaquone and proguanil and doxycyline are well tolerated antimalarial drugs. Broader experience with both agents is needed to accumulate reports of rare adverse events.", "We performed a prospective, double-blind, randomized study to compare the occurrence of neuropsychiatric adverse events and concentration impairment during prophylactic use of either mefloquine or atovaquone plus chloroguanide (INN, proguanil).\n Our potential study population consisted of all persons who were included in the MAL30010 trial at the Travel Clinic, Rotterdam, The Netherlands. All subjects were randomized to receive either active atovaquone (250 mg) plus chloroguanide (100 mg) daily plus a placebo for mefloquine weekly or active mefloquine (250 mg) weekly plus a placebo for atovaquone plus chloroguanide daily. Each subject was followed up from a baseline screening visit up to the index date, 7 days after he or she left the malaria-endemic area. We measured the interindividual and intraindividual changes in mood disturbance by means of the Dutch shortened Profile of Mood States and 3 domains of the Neurobehavioral Evaluation System, which included sustained attention, coding speed, and visuomotor accuracy between baseline and follow-up visit.\n The cohort consisted of 119 subjects with a mean age of 35 years. A significant deterioration in depression, anger, fatigue, vigor, and total mood disturbance domains occurred during use of mefloquine but not during use of atovaquone plus chloroguanide. Stratification for sex showed between-treatment differences in female patients but not in male patients. In both treatment groups, sustained attention deteriorated after travel, especially with increased duration of stay.\n Prophylactic use of mefloquine was associated with significantly higher scores on scales for depression, anger, and fatigue and lower scores for vigor than prophylactic use of atovaquone plus chloroguanide.", "In an open-label trial carried out on the northwest border of Thailand, 1596 patients with uncomplicated multidrug-resistant falciparum malaria were randomly assigned to receive atovaquone-proguanil, atovaquone-proguanil-artesunate, or artesunate-mefloquine and were followed up for 42 days. All 3 regimens were highly effective and well tolerated. Fever duration and parasite clearance times were significantly shorter among patients who received artesunate (P<.001). Polymerase chain reaction genotyping confirmed that recrudescence occurred in 13 patients who received artesunate-mefloquine (2.4%), 5 who received atovaquone-proguanil-artesunate (0.9%), and 15 who received atovaquone-proguanil (2.8%). Adding artesunate to atovaquone-proguanil reduced the risk of failure 3-fold (95% confidence interval [CI], 1.1-8.2) and subsequent gametocyte carriage 21-fold (95% CI, 14-30). Gastrointestinal complaints in the first 48 h after initiation of treatment were more common among artesunate recipients, but after day 2, dizziness, sleep disturbance, nausea, vomiting, and anorexia were more common among mefloquine recipients (P< or =.014). Artesunate-atovaquone-proguanil is a highly effective and well-tolerated treatment for multidrug-resistant falciparum malaria.", "The efficacy and safety of a fixed-dose combination of atovaquone and proguanil hydrochloride (Malarone) were compared with chloroquine or pyrimethamine/sulfadoxine in patients with acute falciparum malaria in northern Peru. Patients were initially randomized to receive 1,000 mg atovaquone and 400 mg proguanil hydrochloride daily for 3 days (n=15) or 1,500 mg chloroquine (base) over a 3 day period (n=14) (phase 1). The cure rate with chloroquine was lower than expected and patients were subsequently randomized to receive a single dose of 75 mg pyrimethamine and 1,500 mg sulfadoxine (n=9) or atovaquone/proguanil as before (n=5) (phase 2). In phase 1, atovaquone/proguanil was significantly more effective than chloroquine (cure rate 100% [14/14] vs. 8% [1/13], P<0.0001). In phase 2, atovaquone/proguanil and pyrimethamine/sulfadoxine were both highly effective (cure rates 100% [5/5] and 100% [7/7]). There were no significant differences between treatment groups in parasite or fever clearance times. Adverse events were typical of malarial symptoms and did not differ significantly between groups. Overall efficacy of atovaquone/proguanil was 100% for treatment of acute falciparum malaria in a region with a high prevalence of chloroquine resistance.", "Chloroquine plus proguanil is widely used for malaria chemoprophylaxis despite low effectiveness in areas where multidrug-resistant malaria occurs. Studies have shown that atovaquone and proguanil hydrochloride is safe and effective for prevention of falciparum malaria in lifelong residents of malaria-endemic countries, but little is known about non-immune travellers.\n In a double-blind equivalence trial, 1083 participants travelling to a malaria-endemic area were randomly assigned to two treatment groups: atovaquone-proguanil plus placebos for chloroquine and proguanil, or chloroquine, proguanil, and placebo for atovaquone-proguanil. Follow-up was by telephone 7 and 60 days after travel and at a clinic at 28 days. Serum samples were tested for antibodies to a malaria circumsporozoite protein. Blood and serum samples of participants with a potential malaria diagnosis were tested in a reference laboratory.\n 7 days after travel, at least one adverse event was reported by 311 (61%) of 511 participants who received atovaquone-proguanil and 329 (64%) of 511 who received chloroquine-proguanil. People receiving atovaquone-proguanil had a lower frequency of treatment-related gastrointestinal adverse events (59 [12%] vs 100 [20%], p=0.001), and of treatment-related adverse events of moderate or severe intensity (37 [7%] vs 56 [11%], p=0.05). There were fewer treatment-related adverse events that caused prophylaxis to be discontinued in the atovaquone-proguanil group than in the chloroquine-proguanil group (one [0.2%] vs ten [2%], p=0.015).\n Overall the two preparations were similarly tolerated. However, significantly fewer adverse gastrointestinal events were observed in the atovaquone-proguanil group in than in the chloroquine-proguanil group." ]	Atovaquone-proguanil and doxycycline are the best tolerated regimens, and mefloquine is associated with adverse neuropsychiatric outcomes.
CD003091	[ "14718419", "15656462", "8245265", "8141537", "14534844", "6096982", "17667837", "7567488", "21712704", "9848045", "20115970", "10024861" ]	[ "Effect of three wound dressings on infection, healing comfort, and cost in patients with sternotomy wounds: a randomized trial.", "Choice of dressing has a major impact on blistering and healing outcomes in orthopaedic patients.", "Randomized trial comparing cryopreserved cultured epidermal allografts with hydrocolloid dressings in healing chronic venous ulcers.", "Influence of occlusive and impregnated gauze dressings on incisional healing: a prospective, randomized, controlled study.", "A prospective randomized evaluation of negative-pressure wound dressings for diabetic foot wounds.", "Comparative study of leg wound skin closure in coronary artery bypass graft operations.", "A silver-coated antimicrobial barrier dressing used postoperatively on meshed autografts: a dressing comparison study.", "A comparison of three wound dressings in patients undergoing heart surgery.", "A prospective randomized trial comparing subatmospheric wound therapy with a sealed gauze dressing and the standard vacuum-assisted closure device.", "A matched-pair, randomized study evaluating the efficacy and safety of Acticoat silver-coated dressing for the treatment of burn wounds.", "A randomized, prospective, controlled study of forearm donor site healing when using a vacuum dressing.", "Reduction of leg wound infections following coronary artery bypass surgery." ]	[ "To compare three dressing types in terms of their ability to protect against infection and promote healing, patient comfort, and cost-effectiveness.\n Prospective, randomized controlled trial.\n Major metropolitan, academically affiliated, tertiary referral center.\n Seven hundred thirty-seven patients were randomized to receive a dry absorbent dressing (n = 243) [Primapore; Smith & Nephew; Sydney, NSW, Australia], a hydrocolloid dressing (n = 267) [Duoderm Thin ConvaTec; Mulgrave, VIC, Australia], or a hydroactive dressing (n = 227) [Opsite; Smith & Nephew] in the operating theater on skin closure.\n There was no difference in the rate of wound infection or wound healing between treatment groups. The Primapore dressing was the most comfortable and cost-effective dressing option for the sternotomy wound. Duoderm Thin dressings were associated with increased wound exudate (p < 0.001), poor dressing integrity (p < 0.001), more frequent dressing changes (p < 0.001), more discomfort with removal (p < 0.05), and increased cost (p < 0.001).\n In the context of no additional benefit for the prevention of wound infection or the rate of wound healing for any of the three dressing products examined, dry absorbent dressings are the most comfortable and cost-effective products for sternotomy wounds following cardiac surgery.", "To investigate the effect of three postoperative dressings on orthopaedic wound healing.\n Three hundred orthopaedic patients were divided into three treatment groups and allocated to management with one of three dressings: Primapore, Tegaderm with pad, and OpSite Post-Op. Staff completed a questionnaire to evaluate the wound progression. Outcome measures were the presence of infection, blistering and the number of dressing changes required.\n There was a significantly lower incidence of blistering with OpSite Post-Op (6%) than Tegaderm with pad (16%) and Primapore (24%) (p<0.001). Patients in the OpSite Post-Op group had the lowest exudate levels.\n Dressings that employ a clear film and have a high moisture vapour transmission rate have been shown to reduce both the rate of blistering and wound discharge. The additional expense inherent in using such dressings may, in reality, prove cost-effective because of the reduced need for dressings changes and the subsequent earlier discharge of these patients from hospital with an uncomplicated wound.", "Cultured epidermal allografts have been successfully used to treat a variety of wounds. Their postulated mechanism of action is through release of cytokines that stimulate epithelialization. On the basis of previous experience we expected ulcers treated with cryopreserved cultured allografts (CCAs) to be healed by 6 weeks. Hydrocolloid dressings (HCDs) have also been reported to be effective in the treatment of venous ulcers.\n Our purpose was to compare the effectiveness of CCAs with HCDs in healing chronic venous ulcers.\n Forty-three patients with 47 ulcers were enrolled in a randomized controlled trial. Ulcers not healed by 6 weeks were changed to the other treatment.\n No difference in the number of healed ulcers between the two groups was observed at 6 weeks. Healing rate, percent reduction of initial ulcer size, and radial progression toward wound closure were significantly greater for CCAs than for HCDs. Pain relief was not significantly different.\n CCAs achieve more rapid healing and greater reduction in ulcer size than HCDs.", "After elective surgery, 28 patients with 40 wounds were enrolled in a controlled clinical study to assess the effects of two different dressings on incisional healing. Patients served as their own control with one-half of each incision covered with an impregnated gauze (Xeroform) and the other half of the incision covered with a thin occlusive hydrocolloid dressing (DuoDerm Extra Thin CGF). All wounds were evaluated 2 to 3 days, 7 to 10 days, 4 weeks, and 7 months postoperatively. None of the incisions segments showed any evidence of infection. At the time of suture removal, the hydrocolloid dressing's ability to contain exudate, protect the wound, and facilitate mobility and personal hygiene were rated higher compared with the gauze-type dressing (p < 0.001, for all variables). At the 4-week visit, both the patient and the surgeon rated the scar segments covered with the hydrocolloid dressing better with respect to color, evenness, and suppleness (p < or = 0.04, for all variables). These differences were no longer apparent 7 months after surgery.", "Optimal treatment for large diabetic foot wounds is ill defined. The purpose of this study was to compare the rate of wound healing with the Vacuum Assisted Closure device trade mark (VAC) to conventional moist dressings in the treatment of large diabetic foot wounds. Diabetics with significant soft tissue defects of the foot were considered for enrollment. Patients were randomized to receive either moist gauze dressings or VAC treatments for 2 weeks, after which they were treated with the alternative dressing for an additional 2 weeks. Wounds were photographed weekly and wound dimensions calculated in a blinded fashion with spatial analysis software. Percent change in wound dimensions were calculated and compared for each weekly assessment and over 2 weeks of therapy with each dressing type. Ten patients were enrolled in the trial, but two were lost to follow-up and two were withdrawn. Complete data were available for analysis on seven wounds in six patients. Average length, width, and depth of the wounds at initiation of the trial was 7.7, 3.5, and 3.1 cm, respectively. Only the wound depth was significantly decreased over the weeks of the trial to 1.2 cm ( p < 0.05). VAC dressings decreased the wound volume and depth significantly more than moist gauze dressings (59% vs. 0% and 49% vs. 8%, respectively). VAC dressings were associated with a decrease in all wound dimensions while wound length and width increased with moist dressings. In summary, over the first several weeks of therapy, VAC dressings decreased wound depth and volume more effectively than moist gauze dressings. Negative-pressure wound treatment may accelerate closure of large foot wounds in the diabetic patient.", "A prospective randomised study of four different methods of leg wound skin closure after removal of the long saphenous vein was carried out in 113 patients undergoing coronary artery bypass grafting. These methods were: (1) continuous nylon vertical mattress suture (27 patients); (2) continuous subcuticular absorbable (Dexon) suture (29 patients); (3) metal skin staples (Autosuture) (27 patients); and (4) adhesive sutureless skin closure (\"Op-site\") (30 patients). All wounds were examined by two independent observers at five, 10, and 45 days after operation. At five days, inflammation, extent of oedema, discharge, and infection were assessed. At 10 days attention was paid to the state of wound healing and at 45 days to the final cosmetic appearance. The use of continuous subcuticular suture resulted in significantly less discharge than did the use of metal staples, nylon vertical mattress suture, or Op-site. The incidence of established wound infection was 4.5% overall, with no infection in the wounds closed with Dexon. Assessment of the healing process showed subcuticular Dexon to be more effective than metal staples or vertical mattress nylon suture. The final cosmetic result showed continuous subcuticular suture to be superior to nylon vertical mattress suture and skin staples but as effective as Op-site sutureless skin closure.", "In an effort to optimize the management of freshly grafted burn wounds, a silver-coated, low-adherence dressing, Acticoat (Smith & Nephew Inc., Largo, FL), was compared with 5% sulfamylon-soaked Exu-Dry burn wound dressings. Twenty subjects admitted to the Loyola University Medical Center were randomized to either Acticoat dressings or 5% sulfamylon-soaked burn wound dressings. Dressings were applied immediately after grafting in the operating room. Acticoat dressings were left in place for 3 days and then changed every 3 days thereafter. Sulfamylon-soaked dressings were changed at 48 hours and then every day. Subjects continued to have dressing changes on a twice-daily basis to wounds that were not grafted managed. Subjects were assessed for graft take, time to wound healing, and the number of dressings required until healing. Hospital charges and labor costs were retrospectively tabulated, yielding an expense estimate for each group. There were no significant differences between the two groups with respect to age, %TBSA, %TBSA of the grafted test sites, graft take, time to graft healing, or infectious complications. The median number of dressing changes to the test site was significantly less in the Acticoat group (P < .05). The average expense per dressing change was not significantly different between the two groups; however, the average total expense per patient was significantly lower for the Acticoat group because of the reduced number of dressing changes. Acticoat and 5% sulfamylon-soaked burn wound dressings were equivalent with respect to wound healing and infectious complications. The use of Acticoat was found to be a safe alternative to the use of 5% sulfamylon as a postsurgical dressing in this group of subjects. Because of the reduced number of dressing changes, the use of Acticoat was a less expensive alternative to 5% sulfamylon dressing changes in this study.", "Two hundred fifty patients undergoing heart surgery were randomized in a prospective comparative study of a semiocclusive hydroactive wound dressing, an occlusive hydrocolloid dressing, and a conventional absorbent dressing. The wounds were evaluated during the 4 weeks after surgery. Color photographs were used for a blind evaluation of wound healing. The conventional absorbent dressing was more effective in wound healing, compared with the hydroactive dressing. Further, there were fewer skin changes and less redness in the wounds with the conventional dressing than with the hydroactive dressing; the differences were not significant with the hydrocolloid dressing. The conventional dressing was less painful to remove than the hydroactive and hydrocolloid dressings. More frequent dressing changes, however, were needed when using the conventional dressing. Despite this, it was the least expensive alternative.", "Two methods of subatmospheric pressure wound therapy--wall suction applied to a sealed gauze dressing (GSUC) and the vacuum-assisted closure device (VAC)--were compared in hospitalized patients at University of Chicago Medical Center.\n VAC therapy is widely used, but can be expensive and difficult to apply; it also fails in some patients.\n A randomized prospective study of 87 patients (N = 45 in the GSUC arm and N = 42 in the VAC arm) was undertaken between October 2006 and May 2008. The study comprised patients with acute wounds resulting from trauma, dehiscence, or surgery.\n Demographics and wound characteristics were similar in both groups. There were significant reductions in wound surface area and volume in each group. In the GSUC group, the reductions in wound surface area and volume were 4.5%/day and 8.4%/day, respectively (P < 0.001 for both), and in the VAC group, this was 4.9%/day and 9.8%/day, respectively (P < 0.001 for both). The reductions in wound surface area and volume were similar in both groups (P = 0.60 and 0.19, respectively, for the group-by-time interaction). The estimated difference (VAC - GSUC) was 0.4% (95% confidence interval: -1.0, 1.7) for wound surface area and 1.4% (95% confidence interval: -0.7, 3.5) for volume. The mean cost per day for GSUC therapy was $4.22 versus $96.51 for VAC therapy (P < 0.01) and the average time required for a GSUC dressing change was 19 minutes versus 31 minutes for a VAC dressing change (P < 0.01). The sum of pain intensity differences was 0.50 in the GSUC group compared with 1.73 for the VAC group (P = 0.02).\n GSUC is noninferior to VAC with respect to changes in wound volume and surface area in an acute care setting. In addition, GSUC dressings were easier to apply, less expensive, and less painful.", "A new silver-coating technology was developed to prevent wound adhesion, limit nosocomial infection, control bacterial growth, and facilitate burn wound care through a silver-coated dressing material. For the purposes of this article, Acticoat (Westaim Biomedical Inc, Fort Saskatchawan, Alberta, Canada) silver-coated dressing was used. After in vitro and in vivo studies, a randomized, prospective clinical study was performed to assess the efficacy and ease of use of Acticoat dressing as compared with the efficacy and ease of our institution's standard burn wound care. Thirty burn patients with symmetric wounds were randomized to be treated with either 0.5% silver nitrate solution or Acticoat silver-coated dressing. The dressing was evaluated on the basis of overall patient comfort, ease of use for the wound care provider, and level of antimicrobial effectiveness. Wound pain was rated by the patient using a visual analog scale during dressing removal, application, and 2 hours after application. Ease of use was rated by the nurse providing wound care. Antimicrobial effectiveness was evaluated by quantitative burn wound biopsies performed before and at the end of treatment. Patients found dressing removal less painful with Acticoat than with silver nitrate, but they found the pain to be comparable during application and 2 hours after application. According to the nurses, there was no statistically significant difference in the ease of use. The frequency of burn wound sepsis (> 10(5) organisms per gram of tissue) was less in Acticoat-treated wounds than in those treated with silver nitrate (5 vs 16). Secondary bacteremias arising from infected burn wounds were also less frequent with Acticoat than with silver nitrate-treated wounds (1 vs 5). Acticoat dressing offers a new form of dressing for the burn wound, but it requires further investigation with greater numbers of patients in a larger number of centers and in different phases of burn wound care.", "1) Compare skin graft healing of the radial forearm free flap (RFFF) donor site when using a negative pressure dressing (NPD) versus a static pressure dressing (SPD). 2) Examine the association of graft size and medical comorbidities with healing of RFFF donor site.\n Randomized, controlled trial.\n Tertiary care hospital.\n After the study was approved, consenting adults undergoing RFFF for head and neck reconstructions were randomized into two arms: SPD and NPD groups. Fifty-four patients were enrolled from March 2007 to August 2009. Pre- and postoperative data were collected, including medical comorbidities, graft size, and area of graft failure/tendon exposure. Data were collected at two postoperative time points.\n The overall wound complication rate was 38 percent (19/50). Wound complications at the first postoperative visit (44.4% [12/27] SPD and 30.4% [7/23] NPD) were not significantly different between groups (P = 0.816). Similarly, wound complications at the second visit (68.8% [11/16] SPD and 80% [12/15] NPD) were not significantly different (P = 0.55). Percentage of area of graft failure between the groups also showed no difference (4.5% SPD vs 7.2% NPD, P = 0.361). The association of graft size with wound complications was analyzed by dividing the data set into three groups (<50 cm(2), 51-100 cm(2), and >100 cm(2)). This difference was not found to be significant (P = 0.428). Finally, when evaluating comorbidities, 50 percent (8/16) of subjects with comorbidities experienced complications compared with 32.4 percent (11/34) without comorbidities, also not reaching significance (P = 0.203).\n Although an attractive option for wound care, the NPD does not appear to offer a significant improvement over an SPD in healing of the RFFF donor site.\n Copyright 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.", "To reduce the rate of infection at the saphenous vein harvest site after coronary artery bypass surgery, to identify predictors of infection and to determine the best method for leg wound closure.\n A randomized clinical trial was undertaken to determine the best technique for reducing the postoperative leg wound infection rate. Patients were allocated to one of four leg wound closure methods: staples, close immediately; staples, close after protamine administration; subcuticular sutures, close immediately; and subcuticular sutures, close after protamine. Risk factors evaluated were age, sex, diabetes, obesity, peripheral vascular disease, reoperation, time in surgery, wound length, wound depth, time that the wound was open, wound quality and harvest site.\n The Walter C Mackenzie Health Sciences Centre, University of Alberta, Edmonton, Alberta.\n All consenting patients undergoing elective coronary artery bypass surgery involving saphenous vein harvesting were considered for the study. Exclusion criteria were insertion of a drain, insertion of an intra-aortic balloon pump in the index limb and inability to complete follow-up at the authors' centre. Eighty patients were initially enrolled, with 77 completing the study.\n Patients underwent standard saphenous vein harvesting followed by wound closure as indicated by the study group.\n The major infection rate was reduced from 13% to 3% (P = 0.02). Each closure method was equally effective, and wound depth was the only factor related to infection.\n Leg wound infections continue to be a major source of morbidity after coronary bypass surgery." ]	At present, there is no evidence to suggest that covering surgical wounds healing by primary intention with wound dressings reduces the risk of SSI or that any particular wound dressing is more effective than others in reducing the rates of SSI, improving scarring, pain control, patient acceptability or ease of dressing removal. Most trials in this review were small and of poor quality at high or unclear risk of bias. However, based on the current evidence, we conclude that decisions on wound dressing should be based on dressing costs and the symptom management properties offered by each dressing type e.g. exudate management.
CD009290	[ "9443139", "11895532", "15605131", "18304848" ]	[ "Labor pain is reduced by massage therapy.", "Effects of massage on pain and anxiety during labour: a randomized controlled trial in Taiwan.", "The effect of breathing and skin stimulation techniques on labour pain perception of Turkish women.", "Massage or music for pain relief in labour: a pilot randomised placebo controlled trial." ]	[ "Twenty-eight women were recruited from prenatal classes and randomly assigned to receive massage in addition to coaching in breathing from their partners during labor, or to receive coaching in breathing alone (a technique learned during prenatal classes). The massaged mothers reported a decrease in depressed mood, anxiety and pain, and showed less agitated activity and anxiety and more positive affect following the first massage during labor. In addition, the massaged mothers had significantly shorter labors, a shorter hospital stay and less postpartum depression.", "To investigate the effects of massage on pain reaction and anxiety during labour.\n Labour pain is a challenging issue for nurses designing intervention protocols. Massage is an ancient technique that has been widely employed during labour, however, relatively little study has been undertaken examining the effects of massage on women in labour.\n A randomized controlled study was conducted between September 1999 and January 2000. Sixty primiparous women expected to have a normal childbirth at a regional hospital in southern Taiwan were randomly assigned to either the experimental (n=30) or the control (n=30) group. The experimental group received massage intervention whereas the control group did not. The nurse-rated present behavioural intensity (PBI) was used as a measure of labour pain. Anxiety was measured with the visual analogue scale for anxiety (VASA). The intensity of pain and anxiety between the two groups was compared in the latent phase (cervix dilated 3-4 cm), active phase (5-7 cm) and transitional phase (8-10 cm).\n In both groups, there was a relatively steady increase in pain intensity and anxiety level as labour progressed. A t-test demonstrated that the experimental group had significantly lower pain reactions in the latent, active and transitional phases. Anxiety levels were only significantly different between the two groups in the latent phase. Twenty-six of the 30 (87%) experimental group subjects reported that massage was helpful, providing pain relief and psychological support during labour.\n Findings suggest that massage is a cost-effective nursing intervention that can decrease pain and anxiety during labour, and partners' participation in massage can positively influence the quality of women's birth experiences.", "To determine the effect of breathing techniques and nurse-administered massage on the pain perception of pregnant woman during labour.\n The present study was conducted among pregnant women (75% primiparous) admitted to the SSK Bakirkoy Women and Children's Hospital (Istanbul, Turkey) between January 1, and September 1, 2000. The patients were in their 38th to 42nd week of pregnancy, not at high risk and expected to have normal vaginal delivery. They were selected from volunteers by nonrandom sampling.\n The present study involved 40 cases, with 20 in the experimental group and 20 in the control group. Data were obtained through the visual analogue scale, inspection form, observation form and postnatal interview form. The study investigators provided information about labour, breathing techniques and massage to the pregnant women assigned to the experimental group at the beginning of labour (latent phase). A study investigator also accompanied them during labour. These women received nurse-administered massage and were encouraged to breathe and perform self-administered massage. They were also instructed to change their positions and to relax.\n Study results demonstrated that nursing support and patient-directed education concerning labour and nonpharmacological pain control methods (eg, breathing and cutaneous stimulation techniques) were effective in reducing the perception of pain by pregnant women (when provided in the latent labour phase before delivery), leading to a more satisfactory birth experience.", "Research on massage therapy for maternal pain and anxiety in labour is currently limited to four small trials. Each used different massage techniques, at different frequencies and durations, and relaxation techniques were included in three trials. Given the need to investigate massage interventions that complement maternal neurophysiological adaptations to labour and birth pain(s), we designed a pilot randomised controlled trial (RCT) to test the effects of a massage programme practised during physiological changes in pain threshold, from late pregnancy to birth, on women's reported pain, measured by a visual analogue scale (VAS) at 90 min following birth. To control for the potential bias of the possible effects of support offered within preparation for the intervention group, the study included 3 arms--intervention (massage programme with relaxation techniques), placebo (music with relaxation techniques) and control (usual care). The placebo offered a non-pharmacological coping strategy, to ensure that use of massage was the only difference between intervention and placebo groups. There was a trend towards slightly lower mean pain scores in the intervention group but these differences were not statistically significant. No differences were found in use of pharmacological analgesia, need for augmentation or mode of delivery. There was a trend towards more positive views of labour preparedness and sense of control in the intervention and placebo groups, compared with the control group. These findings suggest that regular massage with relaxation techniques from late pregnancy to birth is an acceptable coping strategy that merits a large trial with sufficient power to detect differences in reported pain as a primary outcome measure." ]	Massage may have a role in reducing pain, and improving women's emotional experience of labour. However, there is a need for further research.
CD000039	[ "16682611", "17903919", "11306778", "7477798", "15731556", "10528604", "14980943", "15636811" ]	[ "Transdermal glyceryl trinitrate lowers blood pressure and maintains cerebral blood flow in recent stroke.", "The effects of transdermal glyceryl trinitrate, a nitric oxide donor, on blood pressure, cerebral and cardiac hemodynamics, and plasma nitric oxide levels in acute stroke.", "The effect of transdermal glyceryl trinitrate, a nitric oxide donor, on blood pressure and platelet function in acute stroke.", "Propylene glycol toxicity following continuous etomidate infusion for the control of refractory cerebral edema.", "Bendrofluazide fails to reduce elevated blood pressure levels in the immediate post-stroke period.", "Low-dose vasopressin in the treatment of vasodilatory septic shock.", "Prophylactic phenylephrine infusion for preventing hypotension during spinal anesthesia for cesarean delivery.", "Ephedrine and phenylephrine for avoiding maternal hypotension due to spinal anaesthesia for caesarean section. Effects on uteroplacental and fetal haemodynamics." ]	[ "High blood pressure (BP) is common in acute stroke and is independently associated with a poor outcome. Lowering BP might improve outcome if it did not adversely affect cerebral blood flow (CBF) or cerebral perfusion pressure. We investigated the effect of glyceryl trinitrate ([GTN] an NO donor) on quantitative CBF, BP, and cerebral perfusion pressure in patients with recent stroke. Eighteen patients with recent (<5 days) ischemic (n=16) or hemorrhagic (n=2) stroke were randomly assigned (2:1) to transdermal GTN (5 mg) or control. CBF (global, hemispheric, arterial territory, and lesion, using xenon computed tomography) and BP (peripheral and central) were measured before and 1 hour after treatment with GTN. The effects of GTN on CBF and BP were adjusted for baseline measurements (ANCOVA). GTN lowered peripheral systolic BP by (mean) 23 mm Hg (95% CI, 2 to 45; P=0.03) and central systolic BP by 22 mm Hg (95% CI, 0 to 44; P=0.048). In contrast, GTN did not alter CBF (mL/min per 100 g): global -1.2 (95% CI, -6.5 to 4.2; P=0.66) and ipsilateral hemisphere -1.4 (95% CI, -7.6 to 4.9; P=0.65) or area of stroke oligemia, penumbra, or core (as defined by critical CBF limits). Contralateral CBF did not change: hemisphere 0 (95% CI, -7 to 6; P=0.96). GTN did not alter cerebral perfusion pressure or zero-filling pressure. Significant reductions in BP after transdermal GTN are not associated with changes in CBF or cerebral perfusion pressure or cerebral steal in patients with recent stroke. Trials need to assess the effect of lowering BP on functional outcome.", "High blood pressure in acute stroke is common and appears to be associated with a poor outcome. Lowering blood pressure might therefore improve outcome, provided that cerebral perfusion is not compromised. We assessed the effects of glyceryl trinitrate (GTN) on cerebral and systemic hemodynamic measures in acute stroke. Ninety patients with acute ischemic or hemorrhagic stroke were randomized within 72 hours of ictus to transdermal GTN given daily for 10 days (either 5 mg, 5 mg for 4 days then 10 mg, or 10 mg) or control. Twenty-four hour blood pressure monitoring, middle cerebral artery blood velocity, cardiac output, augmentation index, and plasma nitric oxide levels were each measured at baseline and then on days 1, 4, 5, and 10. The primary outcome was blood pressure on day 1. We found that GTN lowered mean peripheral arterial blood pressure on day 1 by 5.3% to 6.7% in a dose dependent manner as compared with control (mean, SD): control, 108.8 (15.1) mmHg; 5 mg, 102.5 (13.9) mmHg; 5/10 mg, 103.4 (14.9) mmHg; 10 mg, 101.5 (12.6) mmHg; (P = .005). Increasing the dose from 5 to 10 mg on day 5 resulted in an overall reduction in blood pressure of 11.4% as compared with leaving the dose at 5 mg (P = .006). GTN reduced peripheral pulse pressure, central aortic blood pressure, pulse pressure, and augmentation index on day 1. Middle cerebral artery blood velocity and pulsatility index in the affected hemisphere, cardiac output, systemic peripheral resistance, and plasma nitric oxide levels were not altered by GTN. Treatment with GTN was associated with headache: control 0 (0%), GTN 9 (15%) (P = .027); no negative effect on end-of-treatment death or deterioration, or 3 month death or dependency was discernable. GTN reduced peripheral blood pressure in a dose-dependent fashion in patients with acute stroke at day 1 and also reduced central blood pressure and augmentation index. In contrast, GTN did not alter middle cerebral artery blood velocity or pulsatility index in the affected hemispheres, suggesting that cerebral blood flow did not change. A trial assessing the effect of lowering blood pressure with GTN on safety and functional outcome in patients with acute stroke is now warranted.", "Hypertension is a common medical complication in acute stroke and is associated with a poor outcome. However, no large trials have assessed the effect of lowering blood pressure (BP) on outcome, and it remains unclear how BP should be managed in acute stroke. We assessed, in a double-blind randomised controlled trial, whether the nitric oxide (NO) donor glyceryl trinitrate (GTN, a known systemic and cerebral vasodilator), would lower BP and alter platelet function.\n Thirty-seven patients with recent (< 5 days) ischaemic or haemorrhagic stroke were randomised by minimisation to 12 days of daily treatment with transdermal GTN or matching placebo patches. Twenty-four-hour ambulatory BP was measured before and during GTN treatment at days 0, 1 and 8. Platelet aggregation and expression of adhesion molecules were assessed at the same time points. Functional outcome (Rankin scale) and case fatality were assessed at 3 months. Analysis was by intention-to-treat.\n GTN significantly lowered BP by 13.0/5.2 mm Hg at day 1 and 9.3/5.0 mm Hg at day 8. The lesser reduction at day 8 than day 1 suggests that tolerance to GTN was developing. Non-significant falls of 0.9/0.6 and 3.8/0.0 mm Hg occurred at days 1 and 8, respectively, in the placebo group. GTN had no effect on heart rate, or platelet aggregation or expression of platelet adhesion molecules, including glycoproteins Ia, Ib, IIIa and P-selectin. Additionally, GTN did not alter case fatality or dependency, although the study was not powered for these outcomes.\n Transdermal GTN, an NO donor, lowered BP by 5-8%, a clinically significant and relevant, but not excessive, degree in patients with acute stroke. However, GTN had no effect on platelet aggregation or expression of adhesion molecules. Since NO donors increase cerebral blood flow in patients with acute ischaemic stroke, GTN may be an appropriate drug for testing the effect of lowering BP on functional outcome.\n Copyright 2001 S. Karger AG, Basel", "Continued elevations in Intracranial Pressure (ICP) following traumatic or ischemic compromise are known to cause markedly increased morbidity and mortality. Because of the side effects of barbiturates including hypotension and prolonged recovery time, the use of shorter-acting anesthetic agents to control ICP has been considered. Etomidate, when administered by continuous infusion, has been shown to decrease cerebral metabolism resulting in a secondary decrease in cerebral blood flow with minimal changes in cerebral perfusion pressure. We initially intended to randomize 20 patients prospectively into a study protocol that would assess the effects of either pentobarbital or the cardioprotective agent etomidate on ICP and cardiac performance. Given the sequelae of the therapy, we were only able to randomize seven patients with cerebral edema refractory to medical management to receive either etomidate or pentobarbital in a blinded fashion. Three patients who received etomidate developed renal compromise (mean low creatinine clearance 41 ml/min, range 37-44 ml/min) which was initially noted at 24 hours. We believed that this represented an adverse effect that was probably related to the study drug and the study was stopped. Each patient received a 0.30 mg/kg IV induction of etomidate and then 0.02 mg/kg/min continuous infusion for 24-72 hours titrated burst suppression. All patients also received dexamethasone 2 mg IV every six hours to prevent the adrenocortical insufficiency that might occur as a consequence of etomidate-induced suppression of cortisol synthesis. Intracranial pressure decreased (mean = 12mmHg) following the initiation of etomidate. Cardiac parameters remained unchanged (cardiac output 4.8 +/- .6 liters/min).(ABSTRACT TRUNCATED AT 250 WORDS)", "Blood pressure (BP) levels, beat-to-beat blood pressure variability, dynamic cerebral autoregulation and cardiac baroreceptor sensitivity are frequently abnormal following acute stroke and are associated with an adverse short- and long-term prognosis. Thiazide diuretics are effective antihypertensive agents in preventing primary and secondary stroke, but their hypotensive and cerebral autoregulatory effects in the immediate post-stroke period have not been studied.\n Thirty-seven hypertensive neuroradiologically proven ischaemic stroke patients were randomized in a double-blind, placebo controlled, parallel group study to bendrofluazide 2.5 mg daily or matching placebo, within 96 h of stroke onset, for a 7-day period. Casual and non-invasive beat-to-beat arterial BP levels, cerebral blood flow velocity, ECG and transcutaneous carbon dioxide levels were measured within 70 +/- 20 h of cerebral infarction and again 7 days later. Dynamic cerebral autoregulatory indices, pulse interval, BP variability and cardiac baroreceptor sensitivity were also calculated.\n Small, non-significant falls were seen in casual and beat-to-beat BP levels over the 7-day period in both active and placebo-treated patients with no differences between treatments. No significant changes were seen in dynamic cerebral autoregulation or in cardiac baroreceptor sensitivity during the follow-up in either group.\n Following acute ischaemic stroke, the standard dose of bendrofluazide at 2.5 mg daily in this study sample did not lower systemic BP levels over the subsequent 7-day period. There was no evidence that bendrofluazide significantly altered cerebral autoregulation or improved cardiac baroreceptor sensitivity post-ictus. Bendrofluazide appears to be an ineffective hypotensive agent at the standard dosage in the initial post-stroke period.\n Copyright 2005 S. Karger AG, Basel.", "Despite appropriate therapy, refractory hypotension often occurs in septic shock. A double-blinded placebo controlled clinical trial was performed to assess the role of low-dose vasopressin (VP) as a pressor agent in septic shock.\n Patients admitted to a trauma intensive care unit with vasodilatory septic shock were randomized to receive either VP at 0.04 U/min (n = 5) or placebo (n = 5). Vasodilatory septic shock was defined as a need for catecholamine agents to maintain a mean arterial pressure more than or equal to 70 mm Hg, despite a cardiac index more than 2.5 L/min and a minimal pulmonary artery wedge pressure more than 12 mm Hg. After 1 hour of initiation of the study drug, attempts to discontinue norepinephrine, phenylephrine, and/or dopamine, in respective order, were undertaken provided that the mean arterial pressure remained more than or equal to 70 mm Hg.\n A vasopressin infusion increased systolic arterial pressure (98 +/- 5 to 125 +/- 8 mm Hg, p < 0.008) because of peripheral vasoconstriction (systemic vascular resistance increased from 878 +/- 218 to 1,190 +/- 213 dynes/s per cm(-5) p < 0.05). Arterial pressure and systemic vascular resistance were statistically unaffected in the placebo group. Before study termination, measured at 24 hours after drug initiation, two patients in the placebo group died of refractory hypotension. However, all patients receiving VP survived the 24-hour study period and had all other catecholamine pressors withdrawn and blood pressure maintained solely with a low-dose VP infusion.\n A VP infusion improved arterial pressure and permitted the withdrawal of catecholamine vasopressors. VP is a useful agent in the treatment of refractory septic shock.", "In a randomized, double-blinded, controlled trial, we investigated the prophylactic infusion of IV phenylephrine for the prevention of hypotension during spinal anesthesia for cesarean delivery. Immediately after intrathecal injection, phenylephrine was infused at 100 microg/min (n = 26) for 3 min. From that point until delivery, phenylephrine was infused at 100 microg/min whenever systolic arterial blood pressure (SAP), measured each minute, was less than baseline. A control group (n = 24) received IV bolus phenylephrine 100 microg after each measurement of SAP <80% of baseline. Phenylephrine infusion decreased the incidence (6 [23%] of 26 versus 21 [88%] of 24; P < 0.0001), frequency, and magnitude (median minimum SAP, 106 mm Hg; interquartile range, 95-111 mm Hg; versus median, 80 mm Hg; range, 73-93 mm Hg; P < 0.0001) of hypotension compared with control. Heart rate was significantly slower over time in the infusion group compared with the control group (P < 0.0001). Despite a large total dose of phenylephrine administered to the infusion group compared with the control group (median, 1260 microg; interquartile range, 1010-1640 microg; versus median, 450 microg; interquartile range, 300-750 microg; P < 0.0001), umbilical cord blood gases and Apgar scores were similar. One patient in each group had umbilical arterial pH <7.2. Prophylactic phenylephrine infusion is a simple, safe, and effective method of maintaining arterial blood pressure during spinal anesthesia for cesarean delivery.\n In patients receiving spinal anesthesia for elective cesarean delivery, a prophylactic infusion of phenylephrine 100 microg/min decreased the incidence, frequency, and magnitude of hypotension with equivalent neonatal outcome compared with a control group receiving IV bolus phenylephrine.", "The effects of i.v. vasopressors on Doppler velocimetry of the maternal uterine and placental arcuate arteries and the fetal umbilical, renal and middle cerebral arteries were studied during spinal anaesthesia in 19 healthy parturients undergoing elective caesarean section. Fetal myocardial function was investigated at the same time by M-mode echocardiography. The patients were randomized into two groups, to be given either ephedrine or phenylephrine as a prophylactic infusion supplemented with minor boluses if systolic arterial pressure decreased by more than 10 mmHg from the control value. Both the vasopressors restored maternal arterial pressure effectively. The ephedrine group showed no significant differences in any of the Doppler velocimetry recordings relative to the baseline values, but during the phenylephrine infusion the blood flow velocity waveform indices for the uterine and placental arcuate arteries increased significantly and vascular resistance decreased significantly in the fetal renal arteries. Healthy fetuses seem to tolerate these changes in uteroplacental circulation well, however, since the Apgar scores for the newborns and the acid-base values in the umbilical cord were within the normal range in both groups. The results suggest that some caution is required when selecting the specific vasopressor agent, the dosage and the mode of administration for the treatment of maternal hypotension secondary to spinal anaesthesia for caesarean section." ]	There is insufficient evidence to evaluate the effect of altering blood pressure on outcome during the acute phase of stroke. In patients with acute stroke, CCBs, ACEI, ARA and GTN each lower blood pressure while phenylephrine probably increases blood pressure.
CD004549	[ "12365120", "3056499", "3074776", "11420821", "12066083", "10804490", "11961377", "15863532" ]	[ "Drainage at caesarean section--a randomised prospective study.", "Closed suction wound drainage and lower-segment caesarean section.", "A controlled trial on wound drainage in caesarean section.", "No benefit from post-caesarean wound drainage.", "Subcutaneous stitch closure versus subcutaneous drain to prevent wound disruption after cesarean delivery: a randomized clinical trial.", "Subcutaneous drain vs. suture in obese women undergoing cesarean delivery. A prospective, randomized trial.", "Value of subcutaneous drainage system in obese females undergoing cesarean section using pfannenstiel incision.", "Subcutaneous tissue reapproximation, alone or in combination with drain, in obese women undergoing cesarean delivery." ]	[ "To determine the efficacy of wound drainage at caesarean section with a view to reducing postoperative wound morbidity.\n King Edward VIII Hospital, Durban, South Africa.\n Four hundred and forty women undergoing emergency caesarean section using the transverse suprapubic incision were randomised to receive either drainage or non-drainage of the wound. Wound drains were removed 48 hours after surgery and patients were seen daily until the time of discharge from hospital. Wound inflammation, wound infection and duration of hospital stay were assessed in both groups.\n Seventy-two of the 440 patients (16.4%) developed wound morbidity ranging from induration, serous, sanguinous and purulent discharge to haematoma formation and wound dehiscence. Of the 217 patients who received drains, 37 showed evidence of wound morbidity (17.1%), as opposed to 35 of the 223 who were not drained (15.7%) (P = 0.701).\n No significant advantages could be demonstrated for routine drainage in terms of wound inflammation, wound infection, haematoma formation or duration of hospital stay.", "In a randomized controlled study of wound suction drainage after transverse suprapubic incision for lower-segment caesarean section no significant advantages could be demonstrated for routine drainage in terms of wound infection, haematoma formation, duration of hospital stay or analgesic requirements.", "A randomized controlled trial was carried out to investigate the influence of drainage on wound infection following Caesarean section. The incidence of clinical wound infection was significantly reduced if a Redivac suction drain was placed beneath the rectus sheath. Subcutaneous corrugated drains were found to offer no advantage. Three different degrees of postoperative pyrexia are examined for their predictive value for the development of wound sepsis. The influence of duration of amnion rupture and the number of vaginal examinations in labour on the postoperative incidence of wound infection and pyrexia are examined.", "A prospective randomized controlled trial to determine the benefit of caesarean wound drainage in 305 low-risk pregnant women.\n Pregnant women at low risk of haemorrhage undergoing caesarean section in the Department of Obstetrics, University Hospital, Zurich, between June 1998 and July 1999 were randomised after informed consent into a no-suction group (n = 154) without post-caesarean wound drainage versus a control group with wound drainage (subfascial and subcutaneous) (n = 151). Outcome measures were perioperative decrease in haemoglobin (Hb), postpartum fever (> 38.5 degrees C for > 2 days), sonographic haematoma and other complications requiring revision, cumulative opiate dose adjusted to body weight, length of hospitalisation and operation time.\n 305 patients completed the study. Decrease in Hb and the rates of fever, haematoma and revision were similar in both groups. However, cumulative opiate dose was lower in the no-suction group (4.5 +/- 1.8 vs 2.8 +/- 1.4 injections, p = 0.0001), and hospital stay was shorter (6.5 +/- 2.4 vs 7.4 +/- 2.8 days, p = 0.0058), as was operation time (32.7 +/- 11.3 v 36.1 +/- 10.5 min; p = 0.0071).\n Routine post-caesarean wound drainage is not only useless but cost-ineffective. In the light of our results, wound drainage may be questioned and should be analysed generally.", "The purpose of this study was to compare a subcutaneous stitch closure and subcutaneous drain placement for the risk of wound disruption after cesarean delivery.\n This was a prospective randomized clinical trial that evaluated subcutaneous stitch closure, placement of a subcutaneous drain, or no closure for subsequent wound disruption risk in women with subcutaneous depth at >or=2 cm.\n The maternal demographics and intrapartum risk factors for postoperative wound disruptions were similar among the 964 study subjects, who were divided into 3 groups. Wound disruptions that required opening of the wound, irrigation, debridement, packing, and/or secondary delayed closure occurred in 9.7% of the women with no closure, 10.4% of the women in the stitch closure group, and 10.3% of the women in the closed drain group (P =.834).\n There appears to be no difference in the subsequent risk of wound complications when no closure of the subcutaneous tissue layers occurs versus suture closure or a closed drainage system.", "To determine if subcutaneous drain or closure of the subcutaneous layer decreases the incidence of wound complications in obese women undergoing cesarean delivery.\n Seventy-six obese women undergoing cesarean delivery and with at least 2 cm of subcutaneous fat were randomized to one of three groups: group 1 had suture closure of the subcutaneous tissue, group 2 had placement of a subcutaneous closed suction drain, and group 3 had neither suture closure nor drainage.\n Wound separation occurred in 12 (15.8%), seroma in 5 (6.6%) and infection in 3 (4%). There were no reports of wound hematoma. The overall incidence of any wound complication (infection, separation, seroma, hematoma) was higher in obese women who received neither subcutaneous suture nor drain as compared to obese women who received either subcutaneous suture closure or subcutaneous drain. The incidence of major wound complications (infection or separation) was also higher in obese women who received neither subcutaneous suture or drain compared to obese women who received either subcutaneous suture closure or subcutaneous drain.\n The use of closed suction drainage in the subcutaneous space may reduce the incidence of postoperative wound complications in obese women who have at least 2 cm of subcutaneous fat and undergo cesarean delivery.", "To determine whether closed subcutaneous drainage systems were efficacious in reducing the rate of wound breakdown of Pfannenstiel incision after cesarean section (CS) in obese females.\n Prospective controlled clinical trial.\n 118 obese pregnant females with a body mass index >32 undergoing CS were divided into two groups: group I (n = 78) with closed subcutaneous drainage system and group II (n = 40) without drainage system. Incision closure technique was standardized. Prophylactic antibiotics were given routinely to both groups.\n Primary outcomes were the incidence of wound breakdown in both groups together with rate of hematoma formation and occurrence of fever. Secondary outcomes were amount of fluid drained, need for redressing.\n Wound breakdown occurred in 9 cases in group I (11.5%), while it happened in 5 cases in group II (12.5%) (p > 0.05). Relative risk was 0.92 (95% CI 0.26-3.75). Hematoma formation was observed in only 1 case in the nondrainage group (group II). Fever was observed in 18 cases in group I (23.1%) in the first 24 h postoperative while in group II, 13 cases developed fever (32.5%) (p > 0.05). The need for redressing within the first 24 h was only in 2.5% of cases in group I while it was 17.9% in group II (p < 0.05).\n We found no significant benefit in using a subcutaneous drain as a prophylactic measure against wound breakdown in obese pregnant females undergoing CS as long as they received a prophylactic antibiotic.\n Copyright 2002 S. Karger AG, Basel", "To compare the efficacy of subcutaneous suture reapproximation alone with suture plus subcutaneous drain for the prevention of wound complications in obese women undergoing cesarean delivery.\n We conducted a multicenter randomized trial of women undergoing cesarean delivery. Consenting women with 4 cm or more of subcutaneous thickness were randomized to either subcutaneous suture closure alone (n = 149) or suture plus drain (n = 131). The drain was attached to bulb suction and removed at 72 hours or earlier if output was less than 30 mL/24 h. The primary study outcome was a composite wound morbidity rate (defined by any of the following: subcutaneous tissue dehiscence, seroma, hematoma, abscess, or fascial dehiscence).\n From April 2001 to July 2004, a total of 280 women were enrolled. Ninety-five percent of women (268/280) had a follow-up wound assessment. Both groups were similar with respect to age, race, parity, weight, cesarean indication, diabetes, steroid/antibiotic use, chorioamnionitis, and subcutaneous thickness. The composite wound morbidity rate was 17.4% (25/144) in the suture group and 22.7% (28/124) in the suture plus drain group (relative risk 1.3, 95% confidence interval 0.8-2.1). Individual wound complication rates, including subcutaneous dehiscence (15.3% versus 21.8%), seroma (9.0% versus 10.6%), hematoma (2.2% versus 2.4%), abscess (0.7% versus 3.3%), fascial dehiscence (1.4% versus 1.7%), and hospital readmission for wound complications (3.5% versus 6.6%), were similar (P > .05) between women treated with suture alone and those treated with suture plus drain, respectively.\n The additional use of a subcutaneous drain along with a standard subcutaneous suture reapproximation technique is not effective for the prevention of wound complications in obese women undergoing cesarean delivery." ]	At present there is no evidence that the routine use of wound drains at caesarean section confers any benefit to the women involved. However, neither moderate benefit nor harm are excluded. These trials do not answer the question of whether wound drainage is of benefit when haemostasis is not felt to be adequate. Further large trials comparing drainage with no drain are justified.
CD001516	[ "17404192", "8726542" ]	[ "Ropinirole 24-hour prolonged release: randomized, controlled study in advanced Parkinson disease.", "Ropinirole in the treatment of levodopa-induced motor fluctuations in patients with Parkinson's disease." ]	[ "To evaluate the efficacy of ropinirole 24-hour prolonged release (ropinirole 24-hour) as an adjunct to levodopa in patients with Parkinson disease (PD) and motor fluctuations.\n In a double-blind, placebo-controlled, 24-week study, 393 subjects with PD were randomized to ropinirole 24-hour (n = 202) or placebo (n = 191). The primary outcome measure was reduction in hours of daily \"off\" time.\n At week 24, the mean dose of ropinirole 24-hour was 18.8 mg/day with a mean reduction in daily levodopa of 278 mg. There was a mean reduction in daily \"off\" time of 2.1 hours in the ropinirole 24-hour group and 0.3 hours with placebo. Secondary outcome measures including change in hours and percent of daily \"on\" time and \"on\" time without troublesome dyskinesia, Unified PD Rating Scale motor and activities of daily living subscales, Beck Depression Inventory-II, PDQ-39 subscales of mobility, activities of daily living, emotional well-being, stigma and communication, and PD Sleep Scale were significantly improved at week 24 with ropinirole 24-hour. The most common adverse events (AE) with ropinirole 24-hour were dyskinesia, nausea, dizziness, somnolence, hallucinations, and orthostatic hypotension and AEs led to study withdrawal in 5% of both the active and placebo groups.\n Ropinirole 24-hour was effective and well tolerated as adjunct therapy in patients with Parkinson disease (PD) not optimally controlled with levodopa. Ropinirole 24-hour demonstrated an improvement in both motor and non-motor PD symptoms, while permitting a reduction in adjunctive levodopa dose.", "Forty-six patients with Parkinson's disease experiencing motor fluctuations and not optimally controlled on levodopa received as adjunct therapy a new nonergoline dopamine agonist, ropinirole, in a 3-month randomized placebo-controlled trial. Ropinirole significantly reduced the duration of off periods as assessed by self-scoring diary cards. There were more nonserious dopaminergic adverse events in the ropinirole group. More patients withdrew because of adverse events or insufficient therapeutic effect in the placebo group. Ropinirole has beneficial adjuvant effects in parkinsonian patients with moderate motor disability and motor fluctuations." ]	Ropinirole therapy can reduce levodopa dose but at the expense of increased dyskinetic adverse events. No clear effect on off time reduction was found but this may have been due to the under-powering of the single evaluable trial. Inadequate data on motor impairments and disability was collected to assess these outcomes. These conclusions apply to short and medium term treatment, up to 26 weeks. Further longer term trials are required, with measurements of effectiveness, and also studies to compare the newer with the older dopamine agonists.
CD000190	[ "3201506", "2696648" ]	[ "Carotid endarterectomy: to shunt or not to shunt.", "Local versus general anaesthesia in carotid surgery. A prospective, randomised study." ]	[ "Because of controversies in the cerebrovascular literature regarding the use of an intraluminal shunt in carotid endarterectomy, we report a randomized prospective study of 118 consecutive symptomatic patients receiving surgery within a single neurosurgical practice. Over 4 years, 138 carotid endarterectomies were performed in the 118 patients, 63 operations with intraluminal shunting and 75 without. Standard rationale for surgery included ipsilateral cerebral infarction in 38% of the operations and ipsilateral transient ischemic attacks in 36%. Unilateral angiographic stenosis of greater than 90% was seen in 58% of the operations; there were no ipsilateral occlusions. Surgery was performed under general anesthesia with barbiturate induction and mild blood pressure elevation. The 30-day complication rate included a mortality rate of 0.7% with a 5.1% incidence of postoperative neurologic deficit and a 1.4% rate of myocardial infarction. In the 24 hours after surgery there were no cerebral infarctions in the shunted group and six in the unshunted group. This 8% rate in the unshunted group compared with 0% in the shunted group was significant at p = 0.023 with a power of 0.95 by Fisher's exact test and chi 2 analysis. This suggests that in our neurosurgical practice (resident training program) the use of an intraluminal shunt during carotid endarterectomy significantly reduces the risk of intraoperative neurologic deficit without increasing the incidence of other complications.", "A randomised, prospective study was performed to compare local (LA) and general anaesthesia (GA) in carotid surgery with special emphasis on complications and the need for intra-operative shunting. Fifty-six patients were randomised to LA and 55 to GA. Eight patients in the LA group required a GA for various reasons. During the same period 14 patients were not randomised. Seven perioperative neurological deficits occurred (5.6%), four in the LA group, two in the GA group, and one in the non-randomised group (NS). Selective shunting was used, in the Ga group according to stump pressure or in cases with a previous stroke and in the LA group according to the appearance of neurological symptoms. In the GA group 25 patients were shunted and in the LA group five patients (P less than 0.001) needed a shunt. If strict pressure criteria for shunting had been used in the LA patients, ten would have been shunted and three of the patients who developed symptoms during clamping would not have been shunted. During surgery the highest recorded systolic pressure was significantly higher in the LA group (210 mmHg versus 173 mmHg, P less than 0.001). LA for carotid endarterectomy is comparable with general anaesthesia regarding peroperative complications but produces significantly higher blood pressures than general anaesthesia. On the other hand it allows the possibility of neurologic monitoring of the patient and leads to significantly less use of an intra-operative shunt." ]	This review concluded that the data available were too limited to either support or refute the use of routine or selective shunting in carotid endarterectomy. It was suggested that large scale randomised trials between routine shunting versus selective shunting were required. No one method of monitoring in selective shunting has been shown to produce better outcomes.
CD001406	[ "18547500" ]	[ "Absorbent products for urinary/faecal incontinence: a comparative evaluation of key product designs." ]	[ "To compare the performance and cost-effectiveness of the key absorbent product designs to provide a more solid basis for guiding selection and purchase. Also to carry out the first stage in the development of a quality of life (QoL) instrument for measuring the impact of absorbent product use on users' lives.\n Three clinical trials focused on the three biggest market sectors. Each trial had a similar crossover design in which each participant tested all products within their group in random order. SETTING, PARTICIPANTS AND INTERVENTIONS: In Trial 1, 85 women with light urinary incontinence living in the community tested three products from each of the four design categories available (total of 12 test products): disposable inserts (pads); menstrual pads; washable pants with integral pad; and washable inserts. In Trial 2a, 85 moderate/heavily incontinent adults (urinary or urinary/faecal) living in the community (49 men and 36 women) tested three (or two) products from each of the five design categories available (total of 14 test products): disposable inserts (with mesh pants); disposable diapers (nappies); disposable pull-ups (similar to toddlers' trainer pants); disposable T-shaped diapers (nappies with waist-band); and washable diapers. All products were provided in a daytime and a (mostly more absorbent) night-time variant. In these first two trials, the test products were selected on the basis of data from pilot studies. In Trial 2b, 100 moderate/heavily incontinent adults (urinary or urinary/faecal) living in 10 nursing homes (27 men and 73 women) evaluated one product from each of the four disposable design categories from Trial 2a. Products were selected on the basis of product performance in Trial 2a and, again, day time and night-time variants were provided. The first phase of developing a QoL tool for measuring the impact of using different pad designs was carried out by interviewing participants from Trials 1 and 2a.\n Product performance (e.g. comfort, discreetness) was characterised using a weekly validated questionnaire. A daily pad change and leakage diary was used to record severity of leakage, numbers of laundry items and pads. Skin health changes were recorded weekly. At a final interview preferences were ranked, acceptability of each design recorded, and overall opinion marked on a visual analogue scale (VAS) of 0-100 points. This VAS score was used to estimate cost-effectiveness. In addition, a timed pad changing exercise was conducted with 10 women from Trial 2b to determine any differences between product designs.\n Disposable inserts are currently the mainstay of management for lightly incontinent women (Trial 1) and they were better for leakage and other variables (but not discreetness) and better overall than the other three designs. However, some women preferred menstrual pads (6/85) or washable pants (13/85), both of which are cheaper to use. Washable inserts were worse both overall and for leakage than the other three designs (72/85 found them unacceptable). For disposable inserts and disposable diapers, findings from the community (Trial 2a) and nursing home trials (Trial 2b) were broadly similar. Leakage performance of disposable inserts was worse than that of the other designs for day and night. Pull-ups were preferred over inserts for the daytime. The new T-shaped diaper was not better overall than the traditional disposable one. However, there were important differences in performance and preference findings for men and women from both trials. Pull-ups (the most expensive) were better overall than the other designs for women during the day and for community-dwelling women during the night. Although disposable diapers were better for leakage than disposable inserts (the cheapest), women did not prefer them (except in nursing homes at night), but for men the diapers were better both overall and for leakage and were the most cost-effective design. No firm conclusions could be drawn about the performance of designs for faecal incontinence. Nursing home carers found pull-ups and inserts easier to apply (in the standing position) and quicker (in the pad change experiment) than the diaper designs; the ability to stand was associated with preference for pull-ups or inserts. The T-shaped diaper was not easier or quicker to change than the diaper. The washable products (Trial 2a) gave diverse results: they were better for leakage at night, but were worse overall for daytime than the other designs. Three-quarters of the women (27/36) found them unacceptable, but nearly two-thirds of men (31/49) found them highly acceptable at night. Findings from the two community trials (Trials 1 and 2a) showed that there were many practical problems in dealing with washable products but, together with the less effective and less expensive products, such as menstrual pads, they were more acceptable at home (and, in the case of washables, at night). This suggests that cost-effective management may involve combining products by using more effective (for a given user) but more expensive designs (e.g. pull-ups) when out and less effective but less expensive designs when at home. The interviews examining the impact of pad use on QoL provided themes and domains that can be further developed into a tool for further evaluation of absorbent products.\n This study showed that there were significant and substantial differences between the designs of absorbent products and for moderate/heavy incontinence some designs are better for men/women than others. There was considerable individual variability in preferences and cost-effective management may best be achieved by allowing users to choose combinations of designs for different circumstances within a budget. Further research is needed into the feasibility of providing choice and combinations of designs to users, as well as into the development of more effective washables and of specifically male disposable products. QoL measurement tools are needed for users of absorbent products, as are clinical trials of designs for community-dwelling carer-dependent men and women with moderate/heavy incontinence." ]	Although data were available from only one eligible trial the data were sufficiently robust to make recommendations for practice. Disposable insert pads are typically more effective than the other designs considered. However, because they are the most expensive, providing choice of designs (or combinations of designs for different circumstances) is likely to be cost-effective.
CD006276	[ "19853518", "9014639" ]	[ "Feasibility study of Transcutaneous Electrical Nerve Stimulation (TENS) for cancer bone pain.", "Randomization is important in studies with pain outcomes: systematic review of transcutaneous electrical nerve stimulation in acute postoperative pain." ]	[ "This multicenter study assessed the feasibility of conducting a phase III trial of transcutaneous electrical nerve stimulation (TENS) in patients with cancer bone pain recruited from palliative care services. Eligible patients received active and placebo TENS for 1 hour at site of pain in a randomized crossover design; median interval between applications 3 days. Responses assessed at 30 and 60 minutes included numerical and verbal ratings of pain at rest and on movement, and pain relief. Recruitment, tolerability, adverse events, and effectiveness of blinding were also evaluated. Twenty-four patients were randomised and 19 completed both applications. The intervention was well tolerated. Five patients withdrew: 3 due to deteriorating performance status, and 2 due to increased pain (1 each following active and placebo TENS). Confidence interval estimation around the differences in outcomes between active and placebo TENS suggests that TENS has the potential to decrease pain on movement more than pain on rest. Nine patients did not consider that a placebo was used; the remaining 10 correctly identified placebo TENS. Feasibility studies are important in palliative care prior to undertaking clinical trials. Our findings suggest that further work is required on recruitment strategies and refining the control arm before evaluating TENS in cancer bone pain.\n Cancer bone pain is common and severe, and partly mediated by hyperexcitability. Animal studies suggest that Transcutaneous Electrical Nerve Stimulation can reduce hyperalgesia. This study examined the feasibility of evaluating TENS in patients with cancer bone pain in order to optimize methods before a phase III trial.\n Copyright 2010 American Pain Society. Published by Elsevier Inc. All rights reserved.", "We set out to examine the evidence for the importance of randomization of transcutaneous electrical nerve stimulation (TENS) in acute postoperative pain. Controlled studies were sought; randomization and analgesic and adverse effect outcomes were summarized. Forty-six reports were identified by searching strategies. Seventeen reports with 786 patients could be regarded unequivocally as randomized controlled trials (RCT) in acute postoperative pain. No meta-analysis was possible. In 15 of 17 RCT, we judged there to be no benefit of TENS compared with placebo. Of the 29 excluded trials, 19 had pain outcomes but were not RCT; in 17 of these 19 TENS studies, the authors concluded that TENS had a positive analgesic effect. No adverse effects were reported. Non-randomized studies overestimated treatment effects." ]	Despite the one additional RCT, the results of this updated systematic review remain inconclusive due to a lack of suitable RCTs. Large multi-centre RCTs are required to assess the value of TENS in the management of cancer-related pain in adults.
CD004052	[ "1728157", "1984763", "11779284", "10770458", "12832240", "10986547", "15056579", "12042191", "10327902" ]	[ "A double-blind comparison of valproate and lithium in the treatment of acute mania.", "Valproate in the treatment of acute mania. A placebo-controlled study.", "Efficacy of olanzapine in combination with valproate or lithium in the treatment of mania in patients partially nonresponsive to valproate or lithium monotherapy.", "Valproate as an adjunct to neuroleptic medication for the treatment of acute episodes of mania: a prospective, randomized, double-blind, placebo-controlled, multicenter study. European Valproate Mania Study Group.", "Olanzapine versus divalproex sodium for the treatment of acute mania and maintenance of remission: a 47-week study.", "Efficacy of olanzapine in acute bipolar mania: a double-blind, placebo-controlled study. The Olanzipine HGGW Study Group.", "Relapse prevention in bipolar I disorder: 18-month comparison of olanzapine plus mood stabiliser v. mood stabiliser alone.", "Olanzapine versus divalproex in the treatment of acute mania.", "Olanzapine versus placebo in the treatment of acute mania. Olanzapine HGEH Study Group." ]	[ "This study was carried out to compare the efficacy of lithium carbonate with that of valproate in acute mania and to determine whether pretreatment clinical characteristics, such as the presence of a mixed affective state, might predict a differential response to the two drugs.\n Twenty-seven patients meeting DSM-III-R criteria for acute manic episodes underwent a 3-week, randomized, double-blind, parallel-groups trial of treatment with lithium carbonate or valproate. Symptom severity was measured by using the Schedule for Affective Disorders and Schizophrenia, change version (SADS-C), the Global Assessment Scale (GAS), and the Brief Psychiatric Rating Scale (BPRS). Drug effects were compared by using repeated measures analysis of variance (ANOVA).\n At the end of the study, nine of 14 patients treated with valproate and 12 of 13 patients treated with lithium had responded favorably, as measured by changes in the SADS-C mania, BPRS, and GAS scores. Elevated pretreatment SADS-C depression scores were associated with good response to valproate. ANOVA revealed a significant interaction between drug and mixed affective state with respect to treatment response.\n Lithium and valproate were both effective in improving manic symptoms, and lithium was slightly more efficacious overall. Unlike the case with lithium, favorable response to valproate was associated with high pretreatment depression scores. Therefore, treatment with valproate alone may be particularly effective in manic patients with mixed affective states.", "We conducted a placebo-controlled, double-blind study of valproate, a drug originally developed as an antiepileptic, in 36 patients with acute manic episodes who had previously failed to respond to or to tolerate lithium carbonate. Treatment duration was 7 to 21 days, with no other psychotropic medications permitted except lorazepam up to 4 mg/d during the first 10 days of treatment. Serum valproate concentrations were measured three times weekly; an unblinded investigator then adjusted dosage to produce serum concentrations between 50 and 100 mg/L. Valproate proved superior to placebo in alleviating manic symptoms. The 17 patients randomized to active drug demonstrated a median 54% decrease in scores on the Young Mania Rating Scale as compared with a median 5.0% decrease among the 19 patients receiving placebo. On the 100-point Global Assessment Scale of overall psychiatric functioning, patients receiving valproate improved by a median of 20 points as compared with a zero-point change with placebo. Significant differences also emerged on the Brief Psychiatric Rating Scale and in the number of supplemental doses of lorazepam required by the patients in each group. Substantial antimanic effects appeared within 1 to 4 days of achieving therapeutic serum valproate concentrations. Adverse effects were infrequent, with no adverse effect appearing significantly more frequently with valproate than with placebo. We conclude that valproate represents a useful new drug for the treatment of manic patients.", "A 6-week double-blind, randomized, placebo-controlled trial was conducted to determine the efficacy of combined therapy with olanzapine and either valproate or lithium compared with valproate or lithium alone in treating acute manic or mixed bipolar episodes.\n The primary objective was to evaluate the efficacy of olanzapine (5-20 mg/d) vs placebo when added to ongoing mood-stabilizer therapy as measured by reductions in Young Mania Rating Scale (YMRS) scores. Patients with bipolar disorder (n = 344), manic or mixed episode, who were inadequately responsive to more than 2 weeks of lithium or valproate therapy, were randomized to receive cotherapy (olanzapine + mood-stabilizer) or monotherapy (placebo + mood-stabilizer).\n Olanzapine cotherapy improved patients' YMRS total scores significantly more than monotherapy (-13.11 vs -9.10; P = .003). Clinical response rates (> or = 50% improvement on YMRS) were significantly higher with cotherapy (67.7% vs 44.7%; P< .001). Olanzapine cotherapy improved 21-item Hamilton Depression Rating Scale (HAMD-21) total scores significantly more than monotherapy (4.98 vs 0.89 points; P< .001). In patients with mixed-episodes with moderate to severe depressive symptoms (DSM-IV mixed episode; HAMD-21 score of > or = 20 at baseline), olanzapine cotherapy improved HAMD-21 scores by 10.31 points compared with 1.57 for monotherapy (P< .001). Extrapyramidal symptoms (Simpson-Angus Scale, Barnes Akathisia Scale, Abnormal Involuntary Movement Scale) were not significantly changed from baseline to end point in either treatment group. Treatment-emergent symptoms that were significantly higher for the olanzapine cotherapy group included somnolence, dry mouth, weight gain, increased appetite, tremor, and slurred speech.\n Compared with the use of valproate or lithium alone, the addition of olanzapine provided superior efficacy in the treatment of manic and mixed bipolar episodes.", "To compare the efficacy of sodium valproate administered as adjunct to neuroleptic medication for patients with acute mania with the efficacy of neuroleptics alone, the authors conducted a 21-day, randomized, double-blind, parallel-group, placebo-controlled trial. The study design closely reflected a clinical psychiatric setting in Europe where patients with acute mania commonly receive neuroleptic medication. In this trial, 136 hospitalized patients met the ICD-10 criteria for acute manic episodes; these patients received a fixed dose of 20 mg/kg of body weight of sodium valproate (Orfiril, Desitin Arzneimittel GmbH, Hamburg, Germany) orally, in addition to basic neuroleptic medication, preferably haloperidol and/or perazine. The primary outcome measure was the mean dose of neuroleptic medication (after conversion into haloperidol-equivalents) for the 21-day study period. Severity of symptoms was measured using the Young Mania Rating Scale (YMRS), the Global Assessment Scale, and the Clinical Global Impression Scale. Intent-to-treat analysis was based on 69 patients treated with valproate and 67 patients who received placebo. Groups were comparable with regard to demographic and clinical baseline data. Premature discontinuations occurred in only 13% of the patients. The mean neuroleptic dose declined continuously in the valproate group, whereas only slight variations were observed in the placebo group; the difference was statistically significant (p = 0.0007) for study weeks 2 and 3. The combination of neuroleptic and valproate proved superior to neuroleptics in attempts to alleviate manic symptoms. The proportion of responders (a 50% improvement rate shown on the YMRS) was higher for the combination with valproate than for the group receiving only neuroleptics (70% vs. 46%; p = 0.005). Adverse events consisted of those known for valproate or neuroleptics; the only adverse event was asthenia, which occurred more frequently with the combination therapy. Valproate represents a useful adjunct medication for the treatment of acute manic symptoms. Valproate is beneficial because it allows the administration of fewer neuroleptic medications and produces improved and quicker remission of manic symptoms.", "Few double-blind trials have compared longer-term efficacy and safety of medications for bipolar disorder. The authors report a 47-week comparison of olanzapine and divalproex.\n This 47-week, randomized, double-blind study compared flexibly dosed olanzapine (5-20 mg/day) to divalproex (500-2500 mg/day) for manic or mixed episodes of bipolar disorder (N=251). The only other psychoactive medication allowed was lorazepam for agitation. The primary efficacy instrument was the Young Mania Rating Scale; a priori protocol-defined threshold scores were > or =20 for inclusion, < or =12 for remission, and > or = 15 for relapse. Analytical techniques included mixed model repeated-measures analysis of variance for change from baseline, Fisher's exact test (two-tailed) for categorical comparisons, and Kaplan-Meier estimates of time to events of interest.\n Over 47 weeks, mean improvement in Young Mania Rating Scale score was significantly greater for the olanzapine group. Median time to symptomatic mania remission was significantly shorter for olanzapine, 14 days, than for divalproex, 62 days. There were no significant differences between treatments in the rates of symptomatic mania remission over the 47 weeks (56.8% and 45.5%, respectively) and subsequent relapse into mania or depression (42.3% and 56.5%). Treatment-emergent adverse events occurring significantly more frequently during olanzapine treatment were somnolence, dry mouth, increased appetite, weight gain, akathisia, and high alanine aminotransferase levels; those for divalproex were nausea and nervousness.\n In this 47-week study of acute bipolar mania, symptomatic remission occurred sooner and overall mania improvement was greater for olanzapine than for divalproex, but rates of bipolar relapse did not differ.", "We compared the efficacy and safety of olanzapine vs placebo for the treatment of acute bipolar mania.\n Four-week, randomized, double-blind, parallel study. A total of 115 patients with a DSM-IV diagnosis of bipolar disorder, manic or mixed, were randomized to olanzapine, 5 to 20 mg/d (n = 55), or placebo (n = 60). The primary efficacy measure was the Young-Mania Rating Scale (Y-MRS) total score. Response and euthymia were defined, a priori, as at least a 50% improvement from baseline to end point and as a score of no less than 12 at end point in the Y-MRS total score, respectively. Safety was assessed using adverse events, Extrapyramidal Symptom (EPS) rating scales, laboratory values, electrocardiograms, vital signs, and weight change.\n Olanzapine-treated patients demonstrated a statistically significant greater mean (+/- SD) improvement in Y-MRS total score than placebo-treated patients (-14.8 +/- 12.5 and -8.1 +/- 12.7, respectively; P<.001), which was evident at the first postbaseline observation 1 week after randomization and was maintained throughout the study (last observation carried forward). Olanzapine-treated patients demonstrated a higher rate of response (65% vs 43%, respectively; P =.02) and euthymia (61% vs 36%, respectively; P =. 01) than placebo-treated patients. There were no statistically significant differences in EPSs between groups. However, olanzapine-treated patients had a statistically significant greater mean (+/- SD) weight gain than placebo-treated patients (2.1 +/- 2.8 vs 0.45 +/- 2.3 kg, respectively) and also experienced more treatment-emergent somnolence (21 patients [38.2%] vs 5 [8.3% ], respectively).\n Olanzapine demonstrated greater efficacy than placebo in the treatment of acute bipolar mania and was generally well tolerated.", "Few controlled studies have examined the use of atypical antipsychotic drugs for prevention of relapse in patients with bipolar I disorder. Aims To evaluate whether olanzapine plus either lithium or valproate reduces the rate of relapse, compared with lithium or valproate alone.\n Patients achieving syndromic remission after 6 weeks'treatment with olanzapine plus either lithium (0.6-1.2 mmol/l) or valproate (50-125 microg/ml) received lithium or valproate plus either olanzapine 5-20 mg/day (combination therapy) or placebo (monotherapy), and were followed in a double-masked trial for 18 months.\n The treatment difference in time to relapse into either mania or depression was not significant for syndromic relapse (median time to relapse: combination therapy 94 days, monotherapy 40.5 days; P=0.742), but was significant for symptomatic relapse (combination therapy 163 days, monotherapy 42 days; P=0.023).\n Patients taking olanzapine added to lithium or valproate experienced sustained symptomatic remission, but not syndromic remission, for longer than those receiving lithium or valproate monotherapy.", "The effects of olanzapine and divalproex for the treatment of mania were compared in a large randomized clinical trial.\n A 3-week, randomized, double-blind trial compared flexibly dosed olanzapine (5-20 mg/day) to divalproex (500-2500 mg/day in divided doses) for the treatment of patients hospitalized for acute bipolar manic or mixed episodes. The Young Mania Rating Scale and the Hamilton Depression Rating Scale were used to quantify manic and depressive symptoms, respectively. Safety was assessed with several measures.\n The protocol defined baseline-to-endpoint improvement in the mean total score on the Young Mania Rating Scale as the primary outcome variable. The mean Young Mania Rating Scale score decreased by 13.4 for patients treated with olanzapine (N=125) and 10.4 for those treated with divalproex (N=123). A priori categorizations defined response and remission rates: 54.4% of olanzapine-treated patients responded (> or = 50% reduction in Young Mania Rating Scale score), compared to 42.3% of divalproex-treated patients; 47.2% of olanzapine-treated patients had remission of mania symptoms (endpoint Young Mania Rating Scale < or = 12), compared to 34.1% of divalproex-treated patients. The decrease in Hamilton depression scale score was similar in the two treatment groups. Completion rates for the 3-week study were similar in both groups. The most common treatment-emergent adverse events (incidence >10%) occurring more frequently during treatment with olanzapine were dry mouth, increased appetite, and somnolence. For divalproex, nausea was more frequently observed. The average weight gain with olanzapine treatment was 2.5 kg, compared to 0.9 kg with divalproex treatment.\n The olanzapine treatment group had significantly greater mean improvement of mania ratings and a significantly greater proportion of patients achieving protocol-defined remission, compared with the divalproex treatment group. Significantly more weight gain and cases of dry mouth, increased appetite, and somnolence were reported with olanzapine, while more cases of nausea were reported with divalproex.", "The primary intent of this study was to compare the efficacy and safety of olanzapine and placebo in the treatment of acute mania.\n The design involved a random-assignment, double-blind, placebo-controlled parallel group study of 3 weeks' duration. After a 2- to 4-day screening period, qualified patients were assigned to either olanzapine (N = 70) or placebo (N = 69). Patients began double-blind therapy with either olanzapine, 10 mg, or placebo given once per day. After the first day of treatment, the daily dose could be adjusted upward or downward, as clinically indicated, by one capsule (olanzapine, 5 mg/day) within the allowed range of one to four capsules. The primary efficacy measure in the protocol was defined as a change from baseline to endpoint in total score on the Young Mania Rating Scale. Clinical response was defined a priori as a decrease of 50% or more from baseline in Young Mania Rating Scale total score.\n The olanzapine group experienced significantly greater mean improvement in Young Mania Rating Scale total score than the placebo group. On the basis of the clinical response criteria, significantly more olanzapine-treated patients (48.6%) responded than those assigned to placebo (24.2%). Somnolence, dizziness, dry mouth, and weight gain occurred significantly more often with olanzapine. There were no statistically significant differences between the olanzapine-treated and placebo-treated patients with respect to measures of parkinsonism, akathisia, and dyskinesias. No discontinuations of treatment due to adverse events occurred in the olanzapine treatment group.\n The results from this study suggest that compared with placebo, olanzapine has superior efficacy for the symptoms of acute mania." ]	There is consistent, if limited, evidence that valproate is an efficacious treatment for acute mania. Valproate may be less efficacious than olanzapine. More, rigorously designed, trials over the full range of acute affective episodes are required.
CD007338	[ "16432349", "12039820", "16035095", "16793612", "18791356", "12357142", "17457160", "8938179", "11896097" ]	[ "Perioperative parenteral tranexamic acid in liver tumor resection: a prospective randomized trial toward a \"blood transfusion\"-free hepatectomy.", "Mechanical methods of reducing blood transfusion in cardiac surgery: randomised controlled trial.", "Efficacy and safety of repeated perioperative doses of recombinant factor VIIa in liver transplantation.", "[Acute normovolemic hemodilution combined with controlled hypotension in patients undergoing liver tumorectomy].", "A prospective randomized trial of acute normovolemic hemodilution compared to standard intraoperative management in patients undergoing major hepatic resection.", "Effectiveness of acute normovolemic hemodilution to minimize allogeneic blood transfusion in major liver resections.", "Intraoperative blood salvage during liver resection: a randomized controlled trial.", "Pilot-controlled trial of the extracorporeal liver assist device in acute liver failure.", "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." ]	[ "To examine the feasibility of a real \"blood transfusion\"-free hepatectomy in a large group of patients with liver tumors.\n Bleeding control and blood transfusion remains problematic in liver resection. A real \"blood transfusion\"-free hepatectomy in a large group of patients has rarely been reported. The impact of tranexamic acid (TA), an antifibrinolytic agent, on blood transfusion in liver resection is unknown.\n A prospective double-blind randomized trial was performed on elective liver tumor resections. In group A, TA 500 mg was intravenously administered just before operation followed by 250 mg, every 6 hours, for 3 days. In group B, only placebo was given. The patients' background, blood transfusion rates, and early postoperative results in the 2 groups were compared. Factors that influenced blood requirement were analyzed.\n There were 108 hepatectomies in group A and 106 hepatectomies in group B. The patients' backgrounds, operative procedures, and hepatectomy extent did not significantly differ between the 2 groups. Although the differences of the operative morbidity and postoperative stay were not significant, a significantly lower amount of operative blood loss, lower blood transfusion rate, shorter operative time, and lower hospital costs were found in group A patients. No patient in group A received blood transfusion. No hospital mortality occurred in either group. Tumor size and use of TA were independent factors that influenced blood transfusion.\n Perioperative parenteral use of TA reduced the amount of operative blood loss and the need for blood transfusion in elective liver tumor resection. A real \"blood transfusion\"-free hepatectomy may be feasible with the assistance of parenteral TA.", "To assess the effectiveness of two mechanical methods of blood conservation in reducing the need for allogeneic red blood cells or coagulation products during cardiac surgery.\n Randomised controlled trial.\n Regional cardiac centre in a teaching hospital in Southampton.\n 263 adults aged 18-80 years undergoing elective coronary artery bypass surgery entered the study, of whom 252 completed the trial. All patients received routine perioperative care. Patients were allocated to one of three treatment groups: intraoperative cell salvage, intraoperative cell salvage with acute perioperative normovolaemic haemodilution, or no mechanical blood conservation. There were 84 patients in each group.\n Numbers of patients who received allogeneic blood or coagulation products, and the mean number of units of blood transfused per patient.\n Of the patients in the intraoperative cell salvage group, 26 were given a transfusion of allogeneic blood, compared with 43 in the control group (odds ratio 0.43 (95% confidence interval 0.23 to 0.80)). The mean number of units of allogeneic blood transfused per patient in the intraoperative cell salvage group was 0.68 units (SD=1.55), compared with 1.07 (1.56) units in the control group. 32 of the patients in the intraoperative cell salvage group were given any blood product, compared with 47 in the control group (odds ratio 0.47 (0.25 to 0.89); P=0.019). Combining acute perioperative normovolaemic haemodilution with intraoperative cell salvage conferred no additional benefits.\n An intraoperative cell salvage device should be used in elective coronary artery bypass grafting. Pharmacological strategies may achieve further reductions in blood transfusions. Yet further reductions in blood transfusions could be achieved if the lower safe limit of haemoglobin concentration in patients undergoing cardiac surgery were known.", "Patients undergoing orthotopic liver transplantation (OLT) have excessive blood loss during surgery that requires blood transfusions, leading to increased postoperative morbidity and mortality. We studied the efficacy and safety of activated recombinant factor VII (rFVIIa) in reducing transfusion requirements in OLT. This multicenter, randomized, double-blind, placebo-controlled trial enrolled patients undergoing OLT because of cirrhosis (Child-Turcotte-Pugh class B or C). Patients received a repeated intravenous bolus regimen of rFVIIa 60 or 120 microg/kg or placebo. The primary efficacy endpoint was the total number of red blood cell (RBC) units transfused during the perioperative period. A total of 182 patients were analyzed for efficacy and 183 for safety. No significant effect of rFVIIa was observed on the number of RBC units transfused or intraoperative blood loss compared with the placebo group. A significantly higher number of patients in the rFVIIa study groups avoided RBC transfusion. Administration of rFVIIa but not placebo restored the preoperative prolonged prothrombin time to normal value during surgery. Patients receiving rFVIIa and placebo did not experience a significant difference in rate of thromboembolic events. Additionally, there was no statistically significant effect of rFVIIa treatment on hospitalization rate, total surgery time, and the proportion of patients undergoing retransplantation. In conclusion, use of rFVIIa during OLT significantly reduced the number of patients requiring RBC transfusion. There was no increase in thromboembolic events with rFVIIa administration compared with placebo.", "To evaluate the effects of acute normovolemic hemodilution (ANH) combined with controlled hypotension on reducing heterogeneous transfusion and safety during liver tumorectomy.\n Thirty patients undergoing elective liver tumorectomy were randomly divided into 3 groups (10 each), namely ANH group (group A), ANH combined with controlled hypotension group (group B) and control group (group C). All the patients were anesthetized via endotracheal intubation. Before the operation, ANH was performed in groups A and B after anesthesia induction, and controlled hypotension was initiated in group B during tumorectomy. Blood transfusion and fluid infusion were carried out routinely in group C. Hb and Hct were measured before operation, after ANH, and immediately, 1 day and 7 days after the operation. The difference in intraoperative blood loss and heterogeneous blood transfusion volume in the 3 groups was observed.\n In group A, heterogeneous blood transfusion was avoided in 6 cases and but given in the other cases for an average of 400 ml. In group C, every patient received heterogeneous blood transfusion (664.8-/+248.1 ml), but none of the patients received heterogeneous blood in group B. The difference in transfusion volume between the 3 groups was significant (P<0.01). Hemodynamics was basically stable during operation in the 3 groups.\n ANH combined with controlled hypotension is safe and effective for decreasing and even avoiding homologous blood transfusion in liver tumorectomy.", "Hepatic resection is the most effective treatment for many malignant and benign conditions affecting the liver and biliary tree. Despite improvements, major partial hepatectomy can be associated with considerable blood loss and transfusion requirements. Transfusion of allogeneic blood products, although potentially life-saving, is associated with many potential complications. The primary aim of this study was to determine if acute normovolemic hemodilution (ANH), an established blood conservation technique, reduces the requirement for allogeneic red cell transfusions in patients undergoing major hepatic resection.\n One hundred thirty patients undergoing major hepatic resection (> or =3 segments) were prospectively randomized to undergo either ANH or standard anesthetic management (STD). In the ANH group, intraoperative blood collection was performed to a target hemoglobin of 8.0 g/dL. Low central venous pressure anesthetic technique was used intraoperatively for both groups. A standardized transfusion protocol was applied to all patients intraoperatively and throughout the hospital stay.\n From April 2004 to March 2007, 63 patients were randomized to ANH and 67 to STD. Demographics, diagnoses, liver function, extent of resection, intraoperative blood loss, operative time, incidence and grade of complications, and length of hospital stay were similar between the 2 groups. ANH reduced the overall allogeneic red cell transfusion rate by 50% compared with STD [12.7% (n = 8) vs. 25.4% (n = 17), respectively; P = 0.067. ANH patients were less often transfused intraoperatively (n = 1, 1.6%) compared with the STD group (n = 7, 10.4%) (P = 0.036), had higher postoperative hemoglobin levels (P = 0.01), and tended to require fewer red cell units overall (28 vs. 47 units). In patients with intraoperative blood loss > or =800 mL, ANH reduced not only the allogeneic red cell transfusion rate (18.2% vs. 42.4%, P = 0.045) but also the proportion of patients requiring fresh frozen plasma (21.1% vs. 48.3%, P = 0.025).\n For patients undergoing major liver resection, ANH is safe, effectively reduces the need for allogeneic transfusions, and should be considered for routine use. Given the modest transfusion rate in the STD arm, future efforts should attempt to target ANH use to patients most likely to benefit.", "Liver resection is a major operation for which, even with the improvements in surgical and anesthetic techniques, the reported rate of blood transfusion was rarely less than 30%. About 60% of transfused patients require only 1 or 2 units of blood, a blood requirement that may be accommodated by the use of acute normovolemic hemodilution (ANH).\n The efficacy, hemodynamic effects, and safety of ANH were investigated in a randomized, active-control study in patients with American Society of Anesthesiologists status I-II who were undergoing major liver resection with fentanyl-nitrous oxide-isoflurane anesthesia. Patients were randomized to the ANH (n = 39) or control group (n = 39). Patients in the ANH group underwent hemodilution to a target hematocrit of 24%. The indication for blood transfusion was standardized. In both groups transfusion was started at a hematocrit of 20%. The primary efficacy endpoint was the avoidance of allogeneic blood transfusion in the intraoperative period and first 72 h after surgery. Various laboratory and hemodynamic parameters as well as postoperative morbidity were monitored to define the safety of ANH in this patient population.\n During the perioperative period, 14 control patients (36%) received at least one unit of allogeneic blood compared with 4 patients (10%) in the ANH group ( < 0.05). The hemodilution process was not associated with significant changes in patients' hemodynamics. Morbidity was similar between the control and the ANH groups. Postoperative hematocrit levels and biochemical liver, renal, and standard coagulation test results were similar in both groups.\n Acute normovolemic hemodilution in patients with American Society of Anesthesiologists status I-II undergoing major liver resection may allow a significant number of patients to avoid exposure to allogeneic blood.", "A randomized controlled trial was conducted to clarify the effectiveness of intraoperative blood salvage in reducing blood loss.\n Although reduction of central venous pressure (CVP) is thought to decrease blood loss during liver resection, no consistently effective and safe method for obtaining the desired reduction of CVP has been established.\n Living liver donors scheduled to undergo liver graft procurement were randomly assigned to a blood salvage group, in which a blood volume equal to approximately 0.7% of the patient's body weight was collected before the liver transection, or a control group. The surgeons were blinded to the randomization results. The primary outcome measure was blood loss during liver parenchymal division. A multivariate analysis was also performed.\n Seventy-nine donors were allocated intraoperatively to the blood salvage group (n = 40) or the control group (n = 39). The amount of blood loss during liver transection was significantly smaller in the blood salvage group than in the control group (median loss during transection, 140 mL vs. 230 mL, P = 0.034). The CVP at the beginning of the liver parenchymal division was significantly lower in the blood salvage group than in the control group (median, 5 cm H2O vs. 6 cm H2O, P = 0.005). The results of a multivariate analysis revealed that intraoperative blood salvage offered the advantage of reduced blood loss during liver parenchymal division (adjusted OR, 0.31; 95% CI, 0.11-0.85, P = 0.025).\n Modest intraoperative blood salvage significantly and safely reduced blood loss during hepatic parenchymal transection.", "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.", "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." ]	None of the interventions seemed to decrease peri-operative morbidity or offer any long-term survival benefit. Haemodilution shows promise in the reduction of blood transfusion requirements in liver resection surgery. However, there is a high risk of type I (erroneously concluding that an intervention is beneficial when it is actually not beneficial) and type II errors (erroneously concluding that an intervention is not beneficial when it is actually beneficial) because of the few trials included, the small sample size in each trial, and the high risk of bias in the trials. Further randomised clinical trials with low risk of bias and random errors that assess clinically important outcomes such as peri-operative mortality are necessary to assess any cardiopulmonary interventions aimed at decreasing blood loss and blood transfusion requirements in patients undergoing liver resections. Trials need to be designed to assess the effect of a combination of different interventions in liver resections.
CD005564	[ "16179089", "11463111", "10403324", "18346028", "17336652", "17292769", "18981499", "17570848", "18545692" ]	[ "A randomized trial of artemether-lumefantrine versus mefloquine-artesunate for the treatment of uncomplicated multi-drug resistant Plasmodium falciparum on the western border of Thailand.", "A clinical and pharmacokinetic trial of six doses of artemether-lumefantrine for multidrug-resistant Plasmodium falciparum malaria in Thailand.", "Efficacy of six doses of artemether-lumefantrine (benflumetol) in multidrug-resistant Plasmodium falciparum malaria.", "High efficacy of two artemisinin-based combinations (artemether-lumefantrine and artesunate plus amodiaquine) for acute uncomplicated malaria in Ibadan, Nigeria.", "Two fixed-dose artemisinin combinations for drug-resistant falciparum and vivax malaria in Papua, Indonesia: an open-label randomised comparison.", "Artemether-lumefantrine versus amodiaquine plus sulfadoxine-pyrimethamine for uncomplicated falciparum malaria in Burkina Faso: a randomised non-inferiority trial.", "A randomized trial of artesunate-mefloquine versus artemether-lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in Mali.", "Efficacy and tolerability of four antimalarial combinations in the treatment of uncomplicated Plasmodium falciparum malaria in Senegal.", "Artemether-lumefantrine versus dihydroartemisinin-piperaquine for treating uncomplicated malaria: a randomized trial to guide policy in Uganda." ]	[ "The use of antimalarial drug combinations with artemisinin derivatives is recommended to overcome drug resistance in Plasmodium falciparum. The fixed combination of oral artemether-lumefantrine, an artemisinin combination therapy (ACT) is highly effective and well tolerated. It is the only registered fixed combination containing an artemisinin. The trial presented here was conducted to monitor the efficacy of the six-dose regimen of artemether-lumefantrine (ALN) in an area of multi-drug resistance, along the Thai-Myanmar border.\n The trial was an open-label, two-arm, randomized study comparing artemether-lumefantrine and mefloquine-artesunate for the treatment of uncomplicated falciparum malaria with 42 days of follow up. Parasite genotyping by polymerase chain reaction (PCR) was used to distinguish recrudescent from newly acquired P. falciparum infections. The PCR adjusted cure rates were evaluated by survival analysis.\n In 2001-2002 a total of 490 patients with slide confirmed uncomplicated P. falciparum malaria were randomly assigned to receive artemether-lumefantrine (n = 245) or artesunate and mefloquine (n = 245) and were followed for 42 days. All patients had rapid initial clinical and parasitological responses. In both groups, the PCR adjusted cure rates by day 42 were high: 98.8% (95% CI 96.4, 99.6%) for artemether-lumefantrine and 96.3% (95% CI 93.1, 98.0%) for artesunate-mefloquine. Both regimens were very well tolerated with no serious adverse events observed attributable to either combination.\n Overall, this study confirms that these two artemisinin-based combinations remain highly effective and result in equivalent therapeutic responses in the treatment of highly drug-resistant falciparum malaria.", "The efficacy-safety and pharmacokinetics of the six-dose regimen of artemether-lumefantrine (Coartem/Riamet; Novartis Pharma AG, Basel, Switzerland) were assessed in a randomized trial in 219 patients (> or = 12 years old) with acute, uncomplicated Plasmodium falciparum malaria in Thailand. One hundred and sixty-four patients received artemether-lumefantrine and 55 received the standard treatment combination of mefloquine-artesunate. Both drugs induced rapid clearance of parasites and malaria symptoms. The 28-day cure rates were 95.5% (90% confidence interval [CI] = 91.7, 97.9%) for artemether-lumefantrine and 100% (90% CI = 94.5, 100%) for mefloquine-artesunate. This high-dose regimen of artemether-lumefantrine was very well tolerated, with very good compliance. The most frequent adverse events were headache, dizziness, nausea, abdominal pain, dyspepsia, vomiting, and skin rash. Overall, only 2% of patients in both groups showed QTc prolongations but without any cardiac complication, and no differences were seen between patients with and without measurable baseline plasma levels of quinine or mefloquine. Plasma levels of artemether, dihydroartemisinin, and lumefantrine were consistent with historical data for the same dose regimen, and were higher, particularly for lumefantrine, than those previously observed with the four-dose regimen, explaining the greater efficacy of the six-dose regimen in a drug-resistant setting. These results confirm the excellent safety and efficacy of the six-dose regimen of artemether-lumefantrine in the treatment of multidrug-resistant P. falciparum malaria.", "The new oral fixed combination artemether-lumefantrine (CGP 56697) has proved to be an effective and well-tolerated treatment of multi-drug resistant Plasmodium falciparum malaria, although cure rates using the four-dose regimen have been lower than with the currently recommended alternative of artesunate-mefloquine. Two six-dose schedules (total adult dose = 480 mg of artemether and 2,880 mg of lumefantrine) were therefore compared with the previously used four-dose regimen (320 mg of artemether and 1,920 mg of lumefantrine) in a double-blind trial involving 359 patients with uncomplicated multidrug-resistant falciparum malaria. There were no differences between the three treatment groups in parasite and fever clearance times, and reported adverse effects. The two six-dose regimens gave adjusted 28-day cure rates of 96.9% and 99.12%, respectively, compared with 83.3% for the four-dose regimen (P < 0.001). These six-dose regimens of artemether-lumefantrine provide a highly effective and very well-tolerated treatment for multidrug-resistant falciparum malaria.", "To test the hypothesis that artesunate plus amodiaquine (ASAQ) is as effective as artemether-lumefantrine (AL) in the treatment of acute uncomplicated malaria in Nigerian children.\n In an open label, randomized controlled clinical trial, children aged 6 months to 10 years were randomized to receive artesunate (4 mg/kg daily) plus amodiaquine (10 mg/kg daily) or AL (5-14 kg, one tablet; 15-24 kg, two tablets and 25-34 kg, three tablets twice daily). Both drug regimens were given for 3 days and follow-up was for 28 days.\n A total of 132 children (66 in each group) were randomized to receive either ASAQ or AL. Day 28 cure rates in the per protocol (PP) population were 93% for ASAQ and 95% for AL (OR = 0.71, 95% CI = 0.12-3.99, rho = 0.66). Using Kaplan-Meier product-limit estimates of failure, the median survival time for ASAQ was 21 days and for AL 28 days (P = 0.294). PCR corrected day 28 cure rate for PP populations were 98.4% for ASAQ and 100% for AL. Both drugs were well-tolerated.\n ASAQ is as effective as AL and both combinations were efficacious and safe.", "The burden of Plasmodium vivax infections has been underappreciated, especially in southeast Asia where chloroquine resistant strains have emerged. Our aim was to compare the safety and efficacy of dihydroartemisinin-piperaquine with that of artemether-lumefantrine in patients with uncomplicated malaria caused by multidrug-resistant P falciparum and P vivax.\n 774 patients in southern Papua, Indonesia, with slide-confirmed malaria were randomly assigned to receive either artemether-lumefantrine or dihydroartemisinin-piperaquine and followed up for at least 42 days. The primary endpoint was the overall cumulative risk of parasitological failure at day 42 with a modified intention-to-treat analysis. This trial is registered with ClinicalTrials.gov, trial number 00157833.\n Of the 754 evaluable patients enrolled, 466 had infections with P falciparum, 175 with P vivax, and 113 with a mixture of both species. The overall risk of failure at day 42 was 43% (95% CI 38-48) for artemether-lumefantrine and 19% (14-23) for dihydroartemisinin-piperaquine (hazard ratio=3.0, 95% CI 2.2-4.1, p<0.0001). After correcting for reinfections, the risk of recrudescence of P falciparum was 4.4% (2.6-6.2) with no difference between regimens. Recurrence of vivax occurred in 38% (33-44) of patients given artemether-lumefantrine compared with 10% (6.9-14.0) given dihydroartemisinin-piperaquine (p<0.0001). At the end of the study, patients receiving dihydroartemisinin-piperaquine were 2.0 times (1.2-3.6) less likely to be anaemic and 6.6 times (2.8-16) less likely to carry vivax gametocytes than were those given artemether-lumefantrine.\n Both dihydroartemisinin-piperaquine and artemether-lumefantrine were safe and effective for the treatment of multidrug-resistant uncomplicated malaria. However, dihydroartemisinin-piperaquine provided greater post-treatment prophylaxis than did artemether-lumefantrine, reducing P falciparum reinfections and P vivax recurrences, the clinical public-health importance of which should not be ignored.", "Artemisinin-based combination regimens are widely advocated for malarial treatment, but other effective regimens might be cheaper and more readily available. Our aim was to compare the risk of recurrent parasitaemia in patients given artemether-lumefantrine with that in those given amodiaquine plus sulfadoxine-pyrimethamine for uncomplicated malaria.\n We enrolled 521 patients aged 6 months or older with uncomplicated falciparum malaria in Bobo-Dioulasso, Burkina Faso. Patients were randomly assigned to receive standard doses of either artemether-lumefantrine (261) or amodiaquine plus sulfadoxine-pyrimethamine (260) for 3 days. Primary endpoints were the risks of treatment failure within 28 days, either unadjusted or adjusted by genotyping to distinguish recrudescence from new infection. The study is registered at controlled-trials.gov with the identifier ISRCTN54261005.\n Of enrolled patients, 478 (92%) completed the 28-day study. The risk of recurrent symptomatic malaria was lowest in the group given amodiaquine plus sulfadoxine-pyrimethamine (1.7%vs 10.2%; risk difference 8.5%; 95% CI 4.3-12.6; p=0.0001); as was the risk of recurrent parasitaemia (4.7%vs 15.1%; 10.4%; 5.1-15.6; p=0.0002). Nearly all recurrences were due to new infections. Recrudescences were four late treatment failures with artemether-lumefantrine and one early treatment failure with amodiaquine plus sulfadoxine-pyrimethamine. Both regimens were safe and well tolerated, with pruritus more common with amodiaquine plus sulfadoxine-pyrimethamine than with artemether-lumefantrine. Each regimen selected for new isolates with mutations that have been associated with decreased drug susceptibility.\n Amodiaquine plus sulfadoxine-pyrimethamine was more effective than was artemether-lumefantrine for the treatment of uncomplicated malaria. For regions of Africa where amodiaquine plus sulfadoxine-pyrimethamine continues to be effective, this less expensive and more available regimen should be considered as an alternative to blanket recommendations for artemisinin-based combination treatment for malaria.", "The choice of appropriate artemisin-based combination therapy depends on several factors (cost, efficacy, safety, reinfection rate, and simplicity of administration). In this study, we tested the hypothesis that artesunate-mefloquine (Artequin) is as efficacious as artemether-lumefantrine (Coartem) in treatment of uncomplicated Plasmodium falciparum malaria. The study was carried out from August 2004 through February 2005 in Kambila, Mali. Subjects with weights >/= 10 kg and uncomplicated malaria were enrolled. Artesunate-mefloquine was given once a day for three days and artemether/lumefantrine twice a day for three days. A total of 470 (235 in each arm) patients were enrolled. The unadjusted 28-day cure rate was higher in artesunate-mefloquine arm than in the artemether-lumefantrine arm (79.7% versus 67.8%; P < 0.004). After correction for reinfection, the 28-day cure rates were similar in the two groups (96.04% versus 96.93%). Artesunate-mefloquine is well-tolerated and is as effective as artemether-lumefantrine for the treatment of P. falciparum malaria. Artesunate-mefloquine also prevented more new infections.", "In view of the high level of chloroquine resistance in many countries, WHO has recommended the use of combination therapy with artemisinin derivatives in the treatment of uncomplicated malaria due to Plasmodium falciparum. Four antimalarial drug combinations, artesunate plus amodiaquine (Arsucam), artesunate plus mefloquine (Artequin), artemether plus lumefantrine (Coartem; four doses and six doses), and amodiaquine plus sulphadoxine-pyrimethamine, were studied in five health districts in Senegal.\n This is a descriptive, analytical, open, randomized study to evaluate the efficacy and tolerability of these four antimalarial combinations in the treatment of uncomplicated falciparum malaria using the 2002 WHO protocol.\n All drug combinations demonstrated good efficacy. On day 28, all combinations resulted in an excellent clinical and parasitological response rate of 100% after correction for PCR results, except for the four-dose artemether-lumefantrine regimen (96.4%). Follow-up of approximately 10% of each treatment group on day 42 demonstrated an efficacy of 100%.The combinations were well tolerated clinically and biologically. No unexpected side-effect was observed and all side-effects disappeared at the end of treatment. No serious side-effect requiring premature termination of treatment was observed.\n The four combinations are effective and well-tolerated.", "Uganda recently adopted artemether-lumefantrine (AL) as the recommended first-line treatment for uncomplicated malaria. However, AL has several limitations, including a twice-daily dosing regimen, recommendation for administration with fatty food, and a high risk of reinfection soon after therapy in high transmission areas. Dihydroartemisinin-piperaquine (DP) is a new alternative artemisinin-based combination therapy that is dosed once daily and has a long post-treatment prophylactic effect. We compared the efficacy and safety of AL with DP in Kanungu, an area of moderate malaria transmission.\n Patients aged 6 months to 10 years with uncomplicated falciparum malaria were randomized to therapy and followed for 42 days. Genotyping was used to distinguish recrudescence from new infection. Of 414 patients enrolled, 408 completed follow-up. Compared to patients treated with artemether-lumefantrine, patients treated with dihydroartemisinin-piperaquine had a significantly lower risk of recurrent parasitaemia (33.2% vs. 12.2%; risk difference = 20.9%, 95% CI 13.0-28.8%) but no statistically significant difference in the risk of treatment failure due to recrudescence (5.8% vs. 2.0%; risk difference = 3.8%, 95% CI -0.2-7.8%). Patients treated with dihydroartemisinin-piperaquine also had a lower risk of developing gametocytaemia after therapy (4.2% vs. 10.6%, p = 0.01). Both drugs were safe and well tolerated.\n DP is highly efficacious, and operationally preferable to AL because of a less intensive dosing schedule and requirements. Dihydroartemisinin-piperaquine should be considered for a role in the antimalarial treatment policy of Uganda.\n Controlled-Trials.com ISRCTN75606663." ]	The six-dose regimen of artemether-lumefantrine appears more effective than antimalarial regimens not containing artemisinin derivatives.
CD006371	[ "10753339", "12670617", "17496674", "15625793" ]	[ "The Psychological Management of Tinnitus: Comparison of a Combined Cognitive Educational Program, Education Alone and a Waiting-List Control.", "The management of chronic tinnitus: comparison of an outpatient cognitive-behavioral group training to minimal-contact interventions.", "Neuromonics Tinnitus Treatment: third clinical trial.", "Treating chronic tinnitus: comparison of cognitive-behavioural and habituation-based treatments." ]	[ "Sixty subjects with chronic tinnitus were randomly allocated to one of three experimental conditions: (1) cognitive coping skills training (attention diversion, imagery training and thought management skills) combined with education. (2) education-only, or (3) waiting-list control. The two treatment groups improved significantly more than the waiting-list control on measures of frequency of use of coping strategies, benefits derived from the use of coping strategies, irrational beliefs and knowledge about tinnitus. Subjects who received the combined cognitive/education intervention demonstrated significantly greater reductions in distress and handicaps associated with tinnitus, and engagement in dysfunctional cognitions, than the subjects who received education alone. No significant effects were obtained on measures of depression, locus of control, or on daily ratings of subjective loudness, noticeability or bothersomeness of the tinnitus. At the 12-month follow-up, the differential treatment effects had dissipated. Although the treatment resulted in statistically significant effects, the size of the clinical effects is rather modest. Implications for the further development of treatment techniques are discussed.", "Using a randomized group design, the efficacy of an outpatient cognitive-behavioral Tinnitus Coping Training (TCT) was compared to two minimal-contact (MC) interventions.\n TCT was conducted in a group format with 11 sessions (total n=43). One MC [MC-E (education), n=16] consisted of two group sessions in which education on tinnitus was presented and self-help strategies were introduced. The second MC [MC-R (relaxation), n=16] comprised four sessions. Besides education, music-supported relaxation was suggested as self-help strategy and audiotapes with relaxing music were provided. Furthermore, a waiting-list control group was installed (WC, n=20). Data were assessed at baseline (pretherapy) and at posttherapy period. Only TCT was additionally evaluated at a 6-month and a 12-month follow-up. Several outcome variables (e.g., awareness of tinnitus) were recorded in a tinnitus diary. Tinnitus coping and disability due to tinnitus were assessed by questionnaires. Subjective ratings of improvement were also requested from the patients. Furthermore, inventories of psychopathology were given to the patients.\n Findings reveal highly significant improvements in TCT in comparison to the control group (WC). MC interventions do not differ significantly from each other, but are superior to WC in a few domains of outcome. Outcome in TCT is somewhat superior to combined MC interventions in two domains of data, but not regarding disability reduction. Effect sizes, nevertheless, indicate distinct differences in degree of improvement, with TCT achieving the best results.\n A sequential scheme for the treatment of chronic tinnitus is discussed on the basis of cost-effectiveness considerations.", "The Neuromonics Tinnitus Treatment combines the use of a novel approach to acoustic stimulation with a structured program of counseling and support by a clinician specifically trained in tinnitus rehabilitation. The distinctive acoustic component has been designed to provide stimulation to auditory pathways deprived by hearing loss, engage positively with the limbic system, and allow intermittent, momentary tinnitus perception within a pleasant and relaxing stimulus, thereby facilitating desensitization to the tinnitus signal. The purposes of this study were (1) to demonstrate the efficacy of the treatment, when enhanced with various modifications since previously reported trials and (2) to test the relative clinical effectiveness of two variations of the approach. In the first, intermittent tinnitus perception was facilitated throughout treatment through the use of a stimulus in which intensity peaks allowed the patients' tinnitus perception to be completely covered up, whereas in the intensity troughs their tinnitus was briefly discernible. In the second, subjects experienced little tinnitus perception while listening to the treatment for the first 2 mo, then experienced intermittent perception.\n Thirty-five subjects with a predominantly moderate to severe level of tinnitus-related distress before treatment were randomly allocated into one of two treatment groups, corresponding to the two stage-based variations of the Neuromonics Tinnitus Treatment. Participants were provided with a high-fidelity personal sound player with earphones and an acoustic stimulus that had been spectrally modified according to their individual audiometric profile. They were instructed to use the acoustic stimulus for at least 2 hr per day, particularly at those times when their tinnitus was usually disturbing. Each group had equal amounts of clinician time for education, monitoring, and support.\n At 2, 4, 6, and 12 mo after commencing treatment, both groups displayed clinically and statistically significant improvements in tinnitus distress, awareness, and minimum masking levels as well as loudness discomfort levels. Improvements increased with time over the first 6 mo of therapy, at which time 91% of all subjects across the two groups reported an improvement in tinnitus disturbance (as measured by the Tinnitus Reaction Questionnaire) of at least 40%, with a mean improvement of 65%. Also, 80% of subjects at 6 mo reported a level of tinnitus disturbance that was no longer clinically significant. There was some indication of a more consistent benefit over 12 mo for the group that was provided initially with a high level of tinnitus interaction; however, inter-group differences were not statistically significant. A relation between reported treatment usage (hours per day) and clinical outcomes was observed, suggesting that a \"dosage effect\" may apply with the stimulus provided.\n This study found that the Neuromonics Tinnitus Treatment provides rapid and profound improvements to the severity of tinnitus symptoms and their effect on the subject's quality of life. This was a consistent effect, provided by a treatment that subjects reported as being pleasant to use. Both of the stage-based variations of the treatment that were tested in this study were shown to be successful in achieving these outcomes.", "Using a randomized control group trial the long-term efficacy of a habituation-based treatment as conceived by Jastreboff, and a cognitive-behavioural tinnitus coping training were compared. An educational intervention was administered as a control condition. Both treatments were conducted in a group format (habituation-based treatment, 5 sessions; tinnitus coping training, 11 sessions). Educational intervention was delivered in a single group session. Patients were categorized according to their level of disability due to tinnitus (low, high), age and gender and then randomly allocated to the treatment conditions (habituation-based treatment, n = 30; tinnitus coping training, n = 27; educational intervention, n = 20). Data assessment included follow-ups of up to 21 months. Several outcome variables including disability due to tinnitus were assessed either by questionnaire or diary. Findings reveal highly significant improvements in both tinnitus coping training and habituation-based treatment in comparison with the control group. While tinnitus coping training and habituation-based treatment do not differ significantly in reduction of tinnitus disability, improvement in general well-being and adaptive behaviour is greater in tinnitus coping training than habituation-based treatment. The decrease in disability remains stable throughout the last follow-up in both treatment conditions." ]	The limited data from the included studies failed to show strong evidence of the efficacy of sound therapy in tinnitus management. The absence of conclusive evidence should not be interpreted as evidence of lack of effectiveness. The lack of quality research in this area, in addition to the common use of combined approaches (hearing therapy plus counselling) in the management of tinnitus are, in part, responsible for the lack of conclusive evidence. Other combined forms of management, such as tinnitus retraining therapy, have been subject to a Cochrane Review. Optimal management may involve multiple strategies.
CD001114	[ "3902388", "6758833", "7032378", "15184205", "20037682", "9364183", "12746252", "12115946", "10095821" ]	[ "Effect of steroid therapy on exercise performance in patients with irreversible chronic obstructive pulmonary disease.", "The use of the 12 minute walking test in assessing the effect of oral steroid therapy in patients with chronic airways obstruction.", "Steroid response in stable chronic obstructive pulmonary disease.", "Peak flow monitoring for guided self-management in childhood asthma: a randomized controlled trial.", "Predictive value and utility of oral steroid testing for treatment of COPD in primary care: the COOPT study.", "The efficacy of inhaled corticosteroids in the management of non asthmatic chronic airflow obstruction.", "Composite spirometric-computed tomography outcome measure in early cystic fibrosis lung disease.", "Use of intravenous pulsed cyclophosphamide in severe, generalized myasthenia gravis.", "The response to inhaled and oral steroids in patients with stable chronic obstructive pulmonary disease." ]	[ "Many patients with irreversible chronic obstructive pulmonary disease (COPD) claim symptomatic improvement with steroid therapy, despite a lack of objective improvement in their spirometric data. To determine if steroids actually increase the exercise capacity of these individuals, 13 clinically stable patients (mean age, 63 +/- 4 years; 12 male patients) were given methylprednisolone (32 mg once daily) or placebo in a randomized double-blind crossover fashion. Spirometric data and minute ventilation, oxygen consumption (VO2), carbon dioxide production, and heart rate during incremental exercise were measured at each visit. Methylprednisolone did not produce a significant change in any of the measured parameters. Three patients had an increase in maximal VO2 of greater than 2 ml/kg/min during therapy with methylprednisolone, while two experienced a decline in maximal VO2 of similar magnitude. The change in exercise capacity was unrelated to the change in the forced expiratory volume in one second in individual patients (r = 0.08). We conclude that in the absence of any improvement in the usual tests of airway mechanics, steroid therapy does not improve exercise performance in patients with COPD.", "The reproducibility of the 12 minute walking distance (12 MD) was assessed in ten men with chronic airways obstruction, and the 12 MD was used, together with spirometry, transfer factor and three subjective assessments of breathlessness to evaluate the effects on respiratory function of prednisone 30 mg daily given orally in double-blind placebo-controlled fashion for two weeks. Like others, we found the 12 MD reproducible on a single day with a mean variation of 3.1%. Tests performed two weeks apart showed greater variability ranging from 0.2% to 30.9%, (mean 9.1%). During placebo and prednisone therapy the 12 MD and assessments of breathlessness correlated significantly with each other and with TLCO, but not with spirometry. Following steroid therapy there was a significant increase in mean TLCO but no significant change in 12 MD, spirometry or subjective assessments. Changes in 12 MD and TLCO correlated significantly with each other and with changes in subjective assessments. Changes in FEV1 correlated with changes in breathlessness, and also with variability in FEV1 while receiving placebo. Individuals with the greatest changes in 12 MD and FEV1 were those with the greatest variability on placebo. The variability of the 12 MD and FEV1 should be measured in individuals before using these tests to assess response to steroid therapy.", "We compared a 2-week course of 32 mg/d methylprednisolone with placebo in a double-blind crossover trial in 46 well-characterized patients with stable chronic obstructive pulmonary disease. Placebo and steroid trials were separated by 2 weeks when no tablets were given. Response was assessed by measuring forced expiratory volume in 1 second (FEV1.0). Placebo responses were normally distributed (mean, 0.8% change in FEV1.0; range, -30% to 33%). Six patients showed a greater than 50% increase of FEV1.0 in response to steroid; a seventh showed a 36% increase and an eighth, a 29% increase. Because of these patients the group as a whole showed a significantly greater FEV1.0 after steroid than after placebo. The eight steroid responders did not differ from nonresponders in age, sex, smoking history, or duration and intensity of symptoms including wheeze. Baseline lung function and eosinophilia of blood or sputum did not differ between the two groups. Patients who responded to steroids also responded to inhaled beta agonists: Acute bronchodilator response averaged 25% in steroid responders and 13% in nonresponders, a difference that was statistically significant although there was overlap between the two groups.", "We asked whether the addition of PEF recordings to a symptom-based self-management plan improved outcome in school children with asthma. In an open-randomized, parallel-group, controlled trial, we studied children aged 7-14 years with moderate asthma. After a 4-week run-in, 90 children were randomized to receive either PEF plus symptom-based management or symptom-based management alone for 12 weeks. Thresholds for action based on PEF were 70% of best (for increasing inhaled steroids) and 50% of best (for commencing prednisolone). Children were asked to perform twice-daily spirometry at home (using an electronic recording spirometer that revealed only PEF to the study group alone) and to record a symptom diary. The mean daily symptom score was the main outcome. There were no differences between groups in mean symptom score or in spirometric lung function, PEF, quality of life score, or reported use of health services over 12 weeks. During acute episodes, children responded to changes in symptoms by increasing their inhaled steroids at a mean value of PEF of greater than 70% of best so that overall PEF did not contribute to this important self-management decision. Knowledge of PEF did not enhance self-management even during acute exacerbations.", "The oral prednisolone test is widely used to distinguish chronic obstructive pulmonary disease (COPD) patients who might benefit from inhaled steroid treatment. Previous studies used selected patient groups that did not represent the large COPD population in primary care.\n The study included smokers and exsmokers with chronic bronchitis or COPD from primary care, who underwent prednisolone testing (30 mg for 14 days) before randomization in a three-year follow-up randomized controlled trial (COOPT Study). Spirometry was performed before and after the test. Responders and nonresponders were classified according to international criteria. Effectiveness of inhaled fluticasone relative to placebo was compared in terms of health status (Chronic Respiratory Disease Questionnaire), exacerbations, and postbronchodilator forced expiratory volume in one second (FEV(1)), using repeated measurement analysis.\n Two hundred eighty-six patients recruited from 44 primary care practices were randomized. Nine percent to 16% of the COPD population was classified as responder, depending on the international guideline criteria used. On average, responders did not reach the minimum clinically important difference in health status (0.29 points/year, P = 0.05), although a borderline significant effect of inhaled fluticasone was noted. Possible clinically relevant reductions in exacerbation rate (rate ratio 0.67) and FEV(1) decline (39 mL/year) occurred in responders, but did not reach statistical significance.\n Oral steroid testing identifies a limited proportion of COPD patients, but does not reveal any clinically relevant benefit from inhaled steroid treatment on health status. No significant effects on exacerbation rate and lung function decline occurred.", "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.", "With the advent of therapies aimed at young patients with cystic fibrosis, who have mildly reduced pulmonary function, the need for improved outcome measures that discriminate treatment effects has become important. Pulmonary function measurements or chest high-resolution computed tomography (HRCT) scores have been separately used to assess interventions. We evaluated these modalities separately and together during a treatment study to develop a more sensitive outcome measure. In a 1-year trial, 25 children randomized either to daily Pulmozyme or to normal saline aerosol were evaluated at randomization and at 3 and 12 months. Outcome variables were pulmonary function test (PFT) results, a global HRCT score, and a composite score incorporating PFTs and HRCT scoring. Regression analyses with generalized estimating equations permitted estimation of the difference in treatment effect between groups over time for each outcome. The largest difference in treatment effects observed at 12 months, measured by the percentage change from baseline, were with the composite total and maximal CT/PFT scores (35.4 and 30.4%), compared with mean forced expiratory flow during the middle half of the FVC (FEF25-75%) (13.0%) and total and maximal global HRCT scores (6.2%, 7.2%). The composite total and maximal CT/PFT scores were the most sensitive outcome measures for discriminating a treatment effect in children with cystic fibrosis with normal or mildly reduced pulmonary function during a 1-year trial of Pulmozyme.", "Twenty-three myasthenia gravis (MG) subjects, mean (SD) age 41.6 years (14), showing poor disease control or steroid-related side effects, received treatment for 12 months with intravenous cyclophosphamide (CP; n = 12) or placebo (PL; n = 11) in a randomized, double-blind trial. Pulses were given monthly at an initial dose of 500 mg/m(2) of body surface, and titrated according to changes of peripheral muscle strength or side effects. Changes of muscle strength, steroid and pyridostigmine requirements, and development of ventilatory failure or swallowing impairment were evaluated at 0, 3, 6, and 12 months. No differences were observed between groups at baseline. Statistically significant reductions of methylprednisone doses were noted in both groups but were more pronounced in subjects receiving CP than PL at 6 months (P < 0.05) and at 12 months (P < 0.03). At 12 months, five subjects on CP had tapered off their steroids whereas no subject on PL achieved further reductions (P < 0.03). Four CP subjects were not receiving steroids 36 months after completing the study and three other CP subjects had stopped pyridostigmine. CP improved muscle strength at 3 and 6 months, and this reached statistical significance compared to PL at 12 months mainly in the bulbar and masticatory (P < 0.009) and extraocular muscles (P < 0.03). Ventilatory failure was noted in one subject on CP (due to bronchopneumonia) and two on PL (due to muscle weakness). No significant increases of CP-related side effects were observed. Thus, this study suggests that intravenous pulses of CP allow reductions of systemic steroids usage without muscle strength deterioration or CP-related side effects.\n Copyright 2002 Wiley Periodicals, Inc.", "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." ]	Oral steroids improved the chest X-ray and a global score of CXR, symptoms and spirometry over 3-24 months. However, there is little evidence of an improvement in lung function. There are limited data beyond two years to indicate whether oral steroids have any modifying effect on long-term disease progression. Oral steroids may be of benefit for patients with Stage 2 and 3 disease with moderate to severe or progressive symptoms or CXR changes.
CD006923	[ "12197575", "14730657", "10373134", "12200524", "11206232", "16424410", "15871441", "9358137", "16925692", "9227720", "7503401", "10069876", "16935685", "9438143", "12357478", "11589265", "15598475", "14529100", "17697902" ]	[ "One-year efficacy and safety of inhaled formoterol dry powder in children with persistent asthma.", "Efficacy and safety of formoterol Turbuhaler when added to inhaled corticosteroid treatment in children with asthma.", "Effect of formoterol on clinical parameters and lung functions in patients with bronchial asthma: a randomised controlled trial.", "Early asthma control and maintenance with eformoterol following reduction of inhaled corticosteroid dose.", "A randomized, 12-week, double-blind, placebo-controlled study comparing formoterol dry powder inhaler with albuterol metered-dose inhaler.", "Formoterol, 24 microg bid, and serious asthma exacerbations: similar rates compared with formoterol, 12 microg bid, with and without extra doses taken on demand, and placebo.", "Efficacy and safety of formoterol delivered via a new multidose dry powder inhaler (Certihaler) in adolescents and adults with persistent asthma.", "Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group.", "Budesonide/formoterol improves lung function compared with budesonide alone in children with asthma.", "Effects of the long acting beta agonist formoterol on asthma control in asthmatic patients using inhaled corticosteroids. The Netherlands and Canadian Formoterol Study Investigators.", "Inhaled formoterol dry powder in the treatment of patients with reversible obstructive airway disease. A 3-month, placebo-controlled comparison of the efficacy and safety of formoterol and salbutamol, followed by a 12-month trial with formoterol.", "Sustained bronchoprotection, bronchodilatation, and symptom control during regular formoterol use in asthma of moderate or greater severity. The Canadian FO/OD1 Study Group.", "Effect of budesonide in combination with formoterol for reliever therapy in asthma exacerbations: a randomised controlled, double-blind study.", "Long-term effects of formoterol and salbutamol on bronchial hyperreactivity and beta-adrenoceptor density on lymphocytes in children with bronchial asthma.", "Budesonide/formoterol in a single inhaler versus inhaled corticosteroids alone in the treatment of asthma.", "Comparison of the efficacy of formoterol and salmeterol in patients with reversible obstructive airway disease: a multicenter, randomized, open-label trial.", "Efficacy, tolerability, and effect on asthma-related quality of life of formoterol bid via multidose dry powder inhaler and albuterol QID via metered dose inhaler in patients with persistent asthma: a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group study.", "Formoterol delivered via the dry powder Aerolizer inhaler versus albuterol MDI and placebo in mild-to-moderate asthma: a randomized, double-blind, double-dummy trial.", "Twelve-week, randomized, placebo-controlled, multicenter study of the efficacy and tolerability of budesonide and formoterol in one metered-dose inhaler compared with budesonide alone and formoterol alone in adolescents and adults with asthma." ]	[ "The long-term efficacy and safety of formoterol dry powder capsules for inhalation in pediatric asthma have not previously been evaluated.\n We examined the effectiveness of inhaled formoterol over a period of 12 months in asthmatic children who were still symptomatic despite anti-inflammatory treatment.\n After a run-in period, 518 patients (5 to 12 years old) were randomized in a double-blind manner to receive 12 or 24 microg formoterol dry powder (Foradil, Novartis Pharma AG, Basel, Switzerland) or placebo twice daily for 12 months. The drug was administered by inhaler (Aerolizer, Novartis Pharma AG) and was given in addition to their anti-inflammatory treatment. The primary variable was the area under the curve for forced expiratory volume in 1 second measured over 12 hours after the morning dose of study medication.\n The area under the curve for forced expiratory volume in 1 second after the first dose of treatment and after 3 and 12 months of treatment was significantly greater for patients receiving formoterol 12 microg and 24 microg than for patients receiving placebo (all P < or = 0.0062). Compared with placebo, both doses of formoterol significantly improved morning and evening premedication peak expiratory flow rate (all P < 0.001). In the group treated with formoterol 24 microg, median symptom score and median dose of rescue medication at night were lower than during the run-in period, whereas the opposite occurred in the placebo group. The incidence of hospitalizations for asthma was higher in the formoterol groups than in the placebo group.\n Our results indicate that, in asthmatic children who are still symptomatic despite anti-inflammatory therapy, the addition of formoterol consistently improves airflow obstruction and nocturnal symptoms and reduces the use of rescue medication. However, this treatment requires close disease monitoring to detect early signs of acute exacerbation.", "This double-blind, placebo-controlled, randomized, parallel-group, multicenter study was conducted in 302 children aged 6-11 years with asthma not optimally treated with inhaled corticosteroids alone. Patients continued with their existing dose of inhaled corticosteroids and in addition received placebo, formoterol 4.5 microg or formoterol 9 microg b.i.d., for 12 weeks (all delivered via Turbuhaler). Terbutaline was available as reliever medication. The primary efficacy variable was change from baseline in morning peak expiratory flow (PEF); secondary efficacy variables included forced expiratory volume in 1 sec (FEV(1)), serial PEF measured over 12 hr, evening PEF, asthma symptom score, and quality of life. Compared with placebo, formoterol 4.5 microg and 9 microg improved morning PEF by 8 l/min (P = 0.035) and 11 l/min (P = 0.0045), respectively. Evening PEF and FEV(1) were also significantly increased compared with placebo, with no statistically significant difference between formoterol doses. Lung-function improvements compared with placebo were greater in the middle of the day. Twelve-hour average serial PEF after 3 months increased by 24 l/min (95% CI, 9, 39 l/min) in the formoterol 9-microg group, and by 14 l/min (95% CI, 0, 29 l/min) in the formoterol 4.5-microg group. The incidence of severe exacerbations in both formoterol groups was numerically lower than in the placebo group, indicating that formoterol may have the potential to improve exacerbation control in children. Both formoterol doses were well-tolerated, and tolerance to the drug's bronchodilator effect was not observed. Formoterol provided sustained improvements in lung function and was well-tolerated in children with asthma suboptimally treated with inhaled corticosteroids alone.\n Copyright 2004 Wiley-Liss, Inc.", "To determine the role of formoterol in the treatment of children with bronchial asthma who are symptomatic despite regular use of inhaled corticosteroids.\n A randomised, double blind, parallel group, placebo controlled study to investigate the effects of inhaled formoterol (12 microg twice a day) in 32 children with moderate to severe bronchial asthma. The study consisted of two week run in periods and six week treatment periods, during both of which the patients continued their regular anti-inflammatory drugs. The efficacy parameters were symptom scores, bronchodilator use, daily peak expiratory flow rates (PEFR), methacholine hyper-reactivity, forced expiratory volume in one second (FEV1), lung volumes, and airway conductance.\n Formoterol treatment for six weeks decreased symptom scores, PEFR variability, and the number of rescue salbutamol doses, and increased morning and evening PEFR significantly. No adverse reactions were seen.\n These findings suggest that inhaled formoterol is effective in controlling chronic asthma symptoms in children who are symptomatic despite regular use of inhaled corticosteroids.", "Previous studies have indicated the benefits of adding long acting beta(2) agonists to inhaled corticosteroids in the maintenance treatment of moderate to severe asthma. The effects of adding eformoterol to corticosteroids on asthma control and exacerbations in patients with mild to moderate asthma were studied.\n After a run in period of 7-14 days on existing medication, 663 symptomatic patients were randomised to receive budesonide Turbohaler 400 microg twice daily together with either eformoterol Turbohaler 9 micro g (delivered dose) or placebo twice daily. After 4 weeks patients whose asthma was well controlled (n=505) were re-randomised to receive budesonide 400 microg daily and either eformoterol 9 micro g or placebo twice daily for a further 6 months.\n Patients receiving eformoterol achieved asthma control 10 days sooner than those receiving budesonide alone, and improvements in lung function, symptoms, quality of life, and relief beta(2) agonist use were significantly greater with eformoterol. During the 6 month follow up the frequency of mild exacerbations was significantly lower in the eformoterol group than in those receiving budesonide alone (7.2 versus 10.5 per patient, 95% confidence interval for ratio 0.49 to 0.96, p=0.03). The time to first day of poorly controlled asthma was 97 days in the eformoterol group compared with 42 days in the placebo group (p=0.003).\n Adding eformoterol to a low or moderate dose of budesonide in mild asthma resulted in faster and more effective control than treatment with budesonide alone. Eformoterol allowed the corticosteroid dose to be reduced while also decreasing the rate of mild exacerbations compared with budesonide alone. These data suggest a therapeutic advantage of adding eformoterol to inhaled corticosteroids in patients with mild to moderate asthma.", "Formoterol is a beta2-adrenergic agent which, when inhaled, produces rapid and long-lasting bronchodilatation.\n The aim of this study was to compare the efficacy, safety, and tolerability of formoterol powder for inhalation delivered via the Aerolizer device with placebo and with albuterol delivered via metered-dose inhaler in patients with mild to moderate persistent asthma.\n In a multicenter, double-blind, parallel-group study, 541 patients were randomized at 26 trial sites to receive either formoterol, 12 microg twice daily; formoterol, 24 microg twice daily; albuterol, 180 microg four times daily; or a placebo for 12 weeks. The effects of each treatment on lung function, asthma symptoms, and frequency of rescue albuterol use were evaluated. Adverse effects and clinical laboratory parameters were also evaluated.\n The bronchodilatory effects of formoterol were rapid in onset and persisted for 12 hours. Both formoterol doses were more effective than placebo and albuterol for objective measures of lung function. Morning and evening peak expiratory flow rates were more improved with formoterol, and formoterol provided significantly greater improvements in asthma symptom scores compared with both albuterol and placebo. Overall, patients taking formoterol used significantly less rescue medication than did those taking albuterol or placebo. Nocturnal awakenings occurred less often with formoterol than with placebo or albuterol. The therapeutic effects of formoterol were maintained over the entire 12 weeks of treatment. Adverse events were similar for all treatment groups, and clinical laboratory data were unremarkable.\n Rapid-onset, long-acting formoterol, administered via the Aerolizer inhaler, is an effective and safe treatment for patients with mild to moderate persistent asthma.", "The primary objective was to determine whether high-dose formoterol, 24 mug bid, was associated with more asthma exacerbations compared with lower formoterol doses in patients with stable persistent asthma. Serious asthma exacerbations (life threatening or requiring hospitalization) were the primary end point. Secondary end points included significant exacerbations requiring systemic corticosteroids, all exacerbations, and changes in FEV1.\n In a multicenter, placebo-controlled, parallel-group study, patients were randomized to 16 weeks of treatment with formoterol, 24 microg bid; formoterol, 12 microg bid, with up to two additional 12-microg doses daily on demand for worsening symptoms (12 microg bid plus on demand); formoterol, 12 microg bid; or placebo. The formoterol 12-microg-bid plus on-demand regimen was administered open label, while the other three regimens were double blind.\n Outpatient clinics.\n A total of 2,085 patients aged > or = 12 years with stable, persistent asthma were enrolled and treated; 65% (n = 1,347) received regular concomitant antiinflammatory therapy during the study.\n Nine patients had respiratory-related serious adverse events (SAEs) requiring hospitalization: two patients (0.4%) in the 24-microg-bid group; one patient (0.2%) in the 12-microg-bid plus on-demand group; five patients (0.9%) in the 12-microg-bid group; and one patient (0.2%) in the placebo group. All of these events were asthma related, except for two SAEs in the 12-microg-bid group that were later considered not to be asthma related by independent reviewers who were not associated with the conduct of the study. The proportions of patients with significant asthma exacerbations (requiring systemic corticosteroids) were similar in the 24-microg-bid group (6.3%, 33 of 527 patients), 12-microg-bid group (5.9%, 31 of 527 patients) and placebo group (8.8%, 45 of 514 patients) and lower in the 12-microg-bid plus on-demand group (4.4%, 23 of 517 patients; p = 0.0057 vs placebo). All treatments were well tolerated. All formoterol treatment regimens had a significant effect on FEV1 measured 2 h after dose during the study (p < 0.0001 vs placebo); and on predose trough FEV1 measured at all visits after baseline (p < 0.002 vs placebo).\n Treatment with formoterol, 24 microg bid, was not associated with an increase in serious asthma exacerbations compared with the lower formoterol doses or placebo.", "Our objective was to compare the efficacy and safety of formoterol (Foradil) delivered via a novel multidose dry powder inhaler (Certihaler) with placebo and albuterol [pressurized metered-dose inhaler (pMDI)], in patients with persistent asthma. After a 2-week run-in phase, 265 patients (13-81 years) previously treated with regular/PRN bronchodilators for persistent asthma were randomized to 12 weeks' double-blind treatment with formoterol 10 microg BID via Certihaler (n = 86), albuterol 180 microg QID via pMDI (n = 88) or placebo (n = 91). The primary efficacy variable was 12-hour AUC of FEV1 after 12 weeks' treatment. Secondary efficacy variables included peak expiratory flow (PEF), rescue bronchodilator medication use, asthma-related quality of life (Juniper Mini Asthma Quality of Life Questionnaire), and asthma symptom scores. Formoterol via the Certihaler had an onset of action within 5 minutes and was associated with a clinically relevant and statistically significant increase in 12-hour AUC of FEV1 after 12 weeks' treatment compared with placebo and albuterol (p < 0.001 and p < 0.05, respectively). Average PEF was significantly superior for formoterol compared with placebo and albuterol (p < 0.001 and p < 0.05, respectively). Compared with placebo, rescue albuterol use during the study was significantly lower for formoterol (p < 0.01) and was accompanied by a trend toward an improvement in asthma-related quality of life (QoL). Asthma symptom scores improved to a similar extent for all treatment groups. Treatment with formoterol via Certihaler was well tolerated. Formoterol 10 microg BID, delivered via the novel Certihaler device, is well tolerated and provides rapid, long-lasting, and clinically superior bronchodilation to placebo and albuterol via pMDI in patients with persistent asthma.", "The role of long-acting, inhaled beta2-agonists in treating asthma is uncertain. In a double-blind study, we evaluated the effects of adding inhaled formoterol to both lower and higher doses of the inhaled glucocorticoid budesonide.\n After a four-week run-in period of treatment with budesonide (800 microg twice daily), 852 patients being treated with glucocorticoids were randomly assigned to one of four treatments given twice daily by means of a dry-powder inhaler (Turbuhaler): 100 microg of budesonide plus placebo, 100 microg of budesonide plus 12 microg of formoterol, 400 microg of budesonide plus placebo, or 400 microg of budesonide plus 12 microg of formoterol. Terbutaline was permitted as needed. Treatment continued for one year; we compared the frequency of exacerbations of asthma, symptoms, and lung function in the four groups. A severe exacerbation was defined by the need for oral glucocorticoids or a decrease in the peak flow to more than 30 percent below the base-line value on two consecutive days.\n The rates of severe and mild exacerbations were reduced by 26 percent and 40 percent, respectively, when formoterol was added to the lower dose of budesonide. The higher dose of budesonide alone reduced the rates of severe and mild exacerbations by 49 percent and 37 percent, respectively. Patients treated with formoterol and the higher dose of budesonide had the greatest reductions -- 63 percent and 62 percent, respectively. Symptoms of asthma and lung function improved with both formoterol and the higher dose of budesonide, but the improvements with formoterol were greater.\n In patients who have persistent symptoms of asthma despite treatment with inhaled glucocorticoids, the addition of formoterol to budesonide therapy or the use of a higher dose of budesonide may be beneficial. The addition of formoterol to budesonide therapy improves symptoms and lung function without lessening the control of asthma.", "We aimed to compare the efficacy and safety of budesonide/formoterol (Symbicort) with budesonide alone (Pulmicort) or budesonide (Pulmicort) and formoterol (Oxis) administered via separate inhalers in children with asthma. In a 12 wk, double-blind study, a total of 630 children with asthma (mean age 8 yr [4-11 yr]; mean forced expiratory volume in 1 s (FEV(1)) 92% predicted; mean inhaled corticosteroid dose 454 microg/day) were randomized to: budesonide/formoterol (80/4.5 microg, two inhalations twice daily); a corresponding dose of budesonide alone (100 microg, two inhalations twice daily); or a corresponding dose of budesonide (100 microg, two inhalations twice daily) and formoterol (4.5 microg, two inhalations twice daily) (budesonide + formoterol in separate inhalers). The primary efficacy variable was the change from baseline to treatment (average of the 12-wk treatment period) in morning peak expiratory flow (PEF). Other changes in lung function and asthma symptoms were assessed, as was safety. Budesonide/formoterol significantly improved morning PEF, evening PEF and FEV(1) compared with budesonide (all p < 0.001); there was no significant difference between budesonide/formoterol and budesonide + formoterol in separate inhalers for these variables. All other diary card variables improved from baseline in all treatment groups; there were no significant between-group differences. Adverse-event profiles were similar in all groups; there were no serious asthma-related adverse events in any treatment group. Conclusion: budesonide/formoterol significantly improved lung function in children (aged 4-11 yr) with asthma compared with budesonide alone. Budesonide/formoterol is a safe and effective treatment option for children with asthma.", "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.", "Inhaled formoterol is a potent selective beta 2-agonist with rapid onset and at least 12-h duration of bronchodilation. The aim of the study was to compare the bronchodilating effect of inhaled formoterol dry powder (dp) 12 micrograms b.i.d. with salbutamol dp 400 micrograms q.i.d. and placebo in patients with reversible obstructive airway disease (ROAD). The study design consisted of a closed 12-week double-blind, placebo-controlled, multicenter trial followed by an open noncomparative, multicenter, 12-month follow-up trial, in which the tolerability of formoterol dp was assessed. A total of 304 patients (146 men, 158 women) aged 18-79 years, ill during 0.1-64 years, were randomized. No demographic or baseline differences were found among the different treatment groups. The bronchodilating effect of formoterol, assessed by morning premedication PEFR, was significantly superior to placebo (P < 0.0001) and salbutamol (P < 0.0001). Efficacy was maintained during the open follow-up study with 12 micrograms b.i.d. in most of the patients. A few patients, however, needed 24 micrograms b.i.d. to control their ROAD. Formoterol 12 micrograms b.i.d. significantly reduced morning and evening asthma symptoms and sleep disturbances, and reduced significantly the need for rescue medication. The tolerability of the three treatment groups was comparable. In conclusion, formoterol 12 micrograms dp b.i.d. was significantly superior to both salbutamol 400 micrograms dp q.i.d. and placebo, and reduced asthma symptoms significantly. Overall, formoterol showed a tolerability profile comparable to that of salbutamol, and no tachyphylaxis was observed during 1 year of treatment.", "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", "The contributions of as-needed inhaled corticosteroids and long-acting beta2 agonists (LABA) to asthma control have not been fully established. We compared the efficacy and safety of three reliever strategies: a traditional short-acting beta2 agonist; a rapid-onset LABA (formoterol); and a combination of LABA and an inhaled corticosteroid (budesonide-formoterol) in symptomatic patients receiving budesonide-formoterol maintenance therapy.\n We did a 12-month, double-blind, parallel-group study in 3394 patients (aged 12 years or older), in 289 centres in 20 countries, who were using inhaled corticosteroids at study entry and symptomatic on budesonide-formoterol (160 microg and 4.5 microg, respectively), one inhalation twice daily, during a 2-week run-in. After run-in, patients were randomly assigned budesonide-formoterol maintenance therapy plus one of three alternative as-needed medications-terbutaline (0.4 mg), formoterol (4.5 microg), or budesonide-formoterol (160 microg and 4.5 microg). The primary outcome was time to first severe exacerbation, defined as an event resulting in hospitalisation, emergency room treatment, or both, or the need for oral steroids for 3 days or more.\n Time to first severe exacerbation was longer with as-needed budesonide-formoterol versus formoterol (p=0.0048; log-rank test) and with as-needed formoterol versus terbutaline (p=0.0051). The rate of severe exacerbations was 37, 29, and 19 per 100 patients per year with as-needed terbutaline, formoterol, and budesonide-formoterol, respectively (rate ratios budesonide-formoterol versus formoterol 0.67 [95% CI 0.56-0.80; p<0.0001]; budesonide-formoterol versus terbutaline 0.52 [0.44-0.62; p<0.0001]; formoterol versus terbutaline 0.78 [0.67-0.91; p=0.0012]). Asthma control days increased to a similar extent in all treatment groups. As-needed formoterol did not significantly improve symptoms compared with as-needed terbutaline. All treatments were well tolerated.\n Both monocomponents of budesonide-formoterol given as needed contribute to enhanced protection from severe exacerbations in patients receiving combination therapy for maintenance.", "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.", "The aim of this study was to evaluate the efficacy (expressed as effect on lung function) and tolerability of Symbicort (budesonide/formoterol in a single inhaler) in children with asthma. This was a double-blind, double-dummy, randomized, parallel-group, multicenter trial. After a 2-4-week run-in period, 286 asthmatic children (177 boys, 109 girls; mean age, 11 years; mean forced expiratory volume in 1 sec (FEV(1)), 75% predicted normal), previously treated with inhaled corticosteroids (average dose 548 microg/day), were randomized to 12 weeks' treatment with either budesonide/formoterol 80/4.5 microg, two inhalations twice daily (n = 148), or an equivalent dose of budesonide 100 microg, two inhalations twice daily (n = 138). Efficacy variables included morning and evening peak expiratory flow (PEF), spirometery, asthma symptoms, and use of rescue medication (beta(2)-agonists). Serial FEV(1) assessments were carried out on a subgroup of children (budesonide/formoterol, n = 41; budesonide, n = 40) at randomization and at week 12. Relative to baseline, morning PEF (primary variable) increased to a significantly greater extent with budesonide/formoterol than with budesonide alone (7.22% predicted normal vs 3.45% predicted normal; P < 0.001). Evening PEF also increased significantly with budesonide/formoterol (6.13% predicted normal vs. 2.73% predicted normal; P < 0.001), as did mean FEV(1) and serial FEV(1) measured over 12 hr (both P < 0.05). Similar improvements in asthma symptoms and rescue medication use were observed in both groups. The two treatment groups were similar in terms of their adverse-event profile and rates of discontinuation. Budesonide/formoterol in a single inhaler provided rapid improvements in PEF and FEV(1) compared to inhaled budesonide alone. These improvements were sustained throughout the study period. Budesonide/formoterol was well-tolerated in children with moderate persistent asthma.\n Copyright 2002 Wiley-Liss, Inc.", "Beta2-adrenergic agonists are frequently used for the prevention and relief of bronchospasm in patients with reversible obstructive airway disease. Formoterol and salmeterol are long-acting beta2-agonists. In addition to its long duration of action, formoterol has been reported to have an onset of action similar to that of albuterol.\n This study compared the effects on lung function of regular twice-daily inhalation of formoterol or salmeterol in adults with moderate to moderately severe persistent asthma who were receiving daily inhaled corticosteroids.\n In this 6-month, multicenter, open-label, parallel-group study, patients with moderate or moderately severe asthma were randomized to receive either formoterol 12 microg BID or salmeterol 50 microg BID. The primary end point was mean morning peak expiratory flow (PEF) measured 5 minutes after dosing and entered in a patient diary each day during the first 4 weeks of treatment. Secondary end points included mean morning and evening predose PEF and number of episode-free days recorded in the patient diaries during the first 4 weeks of treatment, use and time of rescue medication, symptom scores, and overall mean morning predose PEF (spirometric measurements made by the physician during scheduled visits) for the entire treatment period. Safety assessments included spontaneously reported adverse events and vital signs.\n A total of 528 patients were randomized to study treatment, 262 to formoterol and 266 to salmeterol. There were no significant differences in demographic or baseline characteristics between treatment groups, except in the proportion of current smokers in the formoterol group (4.6%) compared with the salmeterol group (1.5%; P = 0.039). Based on the information recorded in patients' diaries, those receiving formoterol showed significant improvement in mean morning PEF measured 5 minutes after dosing (P < 0.001), reduced use of rescue medication (P < 0.03), and an increased number of episode-free days (P < 0.04) compared with patients receiving salmeterol. Mean predose morning and evening PEF and symptom scores based on diary data and mean morning predose PEF based on measurements obtained during office visits were comparable between the 2 treatment groups throughout the study.\n In this open-label trial, patients randomized to formoterol treatment had greater improvement in mean PEF 5 minutes after dosing, required significantly less rescue medication (fewer actuations of albuterol), and experienced more episode-free days compared with patients receiving salmeterol. Thus, although both formoterol and salmeterol are long-acting beta2-agonists, formoterol had a more rapid onset of action.", "Inhaled beta(2)-agonists are widely used in asthma treatment. The design limitations of pressurized metered dose inhalers (pMDIs) have prompted the development of dry powder inhalers (DPIs) for the delivery of asthma medications.\n The goal of this study was to evaluate the efficacy, tolerability, and effect on asthma-related quality of life (QOL) of a long-acting beta(2)-adrenoreceptor agonist, formoterol, delivered via multidose DPI, compared with albuterol delivered via pMDI or placebo in adolescents and adults with persistent asthma.\n This multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group study was conducted in outpatient clinics at 18 US centers. Adolescents and adults with persistent asthma received formoterol 10 pg BID via multidose DPI, albuterol 180 microg QID via pMDI, or placebo for 12 weeks. The primary efficacy variable was the 12-hour AUC of forced expiratory volume in 1 second (FEV(1)) after 12 weeks treatment. Secondary efficacy variables included asthma-related QOL, asthma symptom scores, rescue medication use, and other pulmonary function measures.\n A total of 239 patients (147 females, 92 males; age range, 13-85 years) with persistent asthma were enrolled (formoterol, n = 80; albuterol, n = 79; placebo, n = 80). Formoterol delivered via the multidose DPI resulted in clinically relevant and statistically significant increases in 12-hour AUC of FEV(1) after 12 weeks of treatment compared with albuterol pMDI and placebo (P < 0.019 and P < 0.001, respectively). Asthma-related QOL (total score) was significantly improved with formoterol treatment compared with placebo (P < 0.015). Nocturnal asthma symptom scores significantly improved with formoterol compared with albuterol and placebo (P < 0.001 and P < 0.003, respectively) and rescue medication use was significantly less with formoterol compared with albuterol and placebo (P < 0.004 and P < 0.002, respectively). Treatment with formoterol was well tolerated.\n In this study of adolescents and adults with persistent asthma, 12 weeks of treatment with formoterol 10 microg BID delivered via a multidose DPI provided significantly greater 24-hour bronchodilation compared with albuterol and placebo and resulted in significant improvements in asthma-related QOL compared with placebo. Formoterol was well tolerated in these patients.", "The objectives of this study were to compare the efficacy and tolerability of twice-daily formoterol dry powder 12 microg and 24 microg (Foradil) delivered via Aerolizer inhaler with four times daily albuterol (salbutamol) 180 microg delivered via metered dose inhaler (MDI) and placebo. A total of 554 adolescents and adults (ages 12-75 years) with mild-to-moderate asthma were randomized to this 12-week, multicenter, double-blind, double-dummy, placebo-controlled, parallel-group study. Twelve-hour spirometry measurements were taken at weeks 0, 4, 8, and 12. A total of 484 patients completed the study (122, 116, 127, and 119 given formoterol 12 microg, formoterol 24 microg, albuterol, and placebo, respectively). For the primary efficacy variable, the forced expiratory volume in 1 second (FEV1), both formoterol 12 microg and 24 microg were statistically superior to placebo at all time points on all test days (p < or = 0.017) and to albuterol at most time points on all test days (p < or = 0.001). The onset of improvement in FEV1 was rapid, with 15% increase within 5 min in 57%, 71%, and 65% of formoterol 12 microg, formoterol 24 microg, and albuterol patients, respectively. Formoterol was also superior to placebo and albuterol in terms of secondary efficacy variables: FEV1 area under the curve, percentage of predicted FEV1, forced vital capacity and forced expiratory flow, asthma symptom scores, and peak expiratory flows. In conclusion, both formoterol doses were superior to placebo in all lung function measurements. Overall, compared with albuterol, both formoterol doses produced superior bronchodilation. Formoterol and albuterol were safe and well-tolerated.", "The addition of the long-acting beta(2)-adrenergic agonist formoterol to low- to moderate-dose budesonide has shown clinical efficacy in patients with persistent asthma. Combination therapy with budesonide/formoterol in 1 pressurized metered-dose inhaler (pMDI) has been found to have greater efficacy than its monocomponents in patients with moderate to severe persistent asthma, but it has not been assessed in patients with mild to moderate persistent asthma.\n The aim of this study was to compare the efficacy and tolerability of budesonide and formoterol delivered via 1 pMDI (budesonide/formoterol pMDI), budesonide pMDI, formoterol dry powder inhaler (DPI), and placebo.\n This 12-week, multicenter, double-blind, randomized, placebo-controlled, double-dummy study was conducted at 56 centers across the United States. Patients aged > or =12 years with mild to moderate persistent asthma treated with inhaled corticosteroids (ICSs) for > or =4 weeks before screening and who had a forced expiratory volume in 1 second (FEV(1)) of > or =60% to < or =90% of predicted normal at screening were eligible. After 2 weeks (current asthma therapy discontinued), patients received twice-daily budesonide/formoterol pMDI 80/4.5 microg x 2 inhalations (160/9 microg), budesonide pMDI 80 microg x 2 inhalations (160 microg), formoterol DPI 4.5 microg x 2 inhalations (9 microg), or placebo. The coprimary efficacy variables were changes from baseline in morning predose FEV(1) and 12-hour mean FEV(1) (from serial spirometry) after administration of the morning dose of study medication. Tolerability was assessed based on adverse events (AEs); routine laboratory assessments; electrocardiography; 24-hour Holter monitor assessments; and physical examinations, including vital signs (eg, systolic and diastolic blood pressure and heart rate). AEs were recorded manually by the patient in paper notebooks and reviewed at each clinic visit by the investigator and during a final follow-up phone call.\n A total of 480 patients were randomized (299 females, 181 males; mean age, 36 years; mean FEV(1), 2.4 L; budesonide/formoterol pMDI, 123 patients; budesonide pMDI, 121; formoterol DPI, 114; placebo, 122). At end of treatment, the mean increases from baseline in predose FEV(1) were greater with budesonide/formoterol pMDI versus budesonide pMDI, formoterol DPI, and placebo (0.37 vs 0.23, 0.17, and 0.03 L, respectively; all, P<0.005). 0.005). After administration of the first dose and at weeks 2 and 12, mean increases in 12-hour mean FEV(1) were significantly greater with budesonide/formoterol pMDI (0.41, 0.47, and 0.50 L, respectively) versus budesonide pMDI (0.17, 0.30, and 0.32 L) and placebo (0.15, 0.12, and 0.12 L) (all, P < 0.001). Fewer patients receiving budesonide/formoterol pMDI met criteria for (18.7%; P < 0.001) or withdrew because of (7.3%; P < or = 0.010) worsening asthma versus formoterol DPI (42.1% and 18.4%, respectively) and placebo (56.6% and 32.8%); results were similar between budesonide pMDI (21.5% and 6.6%, respectively) and budesonide/formoterol pMDI. Three patients experienced serious AEs; none was considered related to study medication. The proportions of withdrawals due to worsening asthma were not significantly different between the budesonide/formoterol pMDI and budesonide pMDI groups.\n In this population of adults and adolescents with mild to moderate persistent asthma previously treated with ICSs, twice-daily budesonide/formoterol pMDI was associated with significantly increased pulmonary function versus its monocomponents. All study drugs were generally well tolerated." ]	In comparison with placebo, we have found an increased risk of serious adverse events with regular formoterol, and this does not appear to be abolished in patients taking inhaled corticosteroids. The effect on serious adverse events of regular formoterol in children was greater than the effect in adults, but the difference between age groups was not significant. Data on all-cause serious adverse events should be more fully reported in journal articles, and not combined with all severities of adverse events or limited to those events that are thought by the investigator to be drug-related.
CD001060	[ "17169012", "12057549", "14645308", "1319808", "2206069", "6708033", "12066082", "10580682", "18753646", "8238157", "7980301", "9532990", "9916961", "2276652", "7900522", "7769899", "2180472", "10601925", "4073155", "7839282" ]	[ "Magnesium sulphate given before very-preterm birth to protect infant brain: the randomised controlled PREMAG trial*.", "Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial.", "Effect of magnesium sulfate given for neuroprotection before preterm birth: a randomized controlled trial.", "[Magnesium sulfate in prevention of preterm labor].", "Randomized investigation of magnesium sulfate for prevention of preterm birth.", "Comparison of magnesium sulfate, terbutaline and a placebo for inhibition of preterm labor. A randomized study.", "Association between the use of antenatal magnesium sulfate in preterm labor and adverse health outcomes in infants.", "Prevention of preterm delivery: nifedipine or magnesium sulfate.", "A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy.", "Efficacy and safety of nifedipine versus magnesium sulfate in the management of preterm labor: a randomized study.", "A safer and more effective treatment regimen for eclampsia.", "A randomised controlled trial of intravenous magnesium sulphate versus placebo in the management of women with severe pre-eclampsia.", "Randomized comparison of intravenous nitroglycerin and magnesium sulfate for treatment of preterm labor.", "[Tocolytic therapy with magnesium sulfate and terbutaline for inhibition of premature labor].", "Expectant management in severe preeclampsia: does magnesium sulfate prevent the development of eclampsia?", "Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial.", "Magnesium sulphate versus diazepam in the management of eclampsia: a randomized controlled trial.", "Oral nicardipine versus intravenous magnesium sulfate for the treatment of preterm labor.", "A comparison of ritodrine, terbutaline, and magnesium sulfate for the suppression of preterm labor.", "Intravenous and intramuscular magnesium sulphate regimens in severe pre-eclampsia." ]	[ "To evaluate whether magnesium sulphate (MgSO(4)) given to women at risk of very-preterm birth would be neuroprotective in preterm newborns and would prevent neonatal mortality and severe white-matter injury (WMI).\n A randomised study.\n Eighteen French tertiary hospitals. Population Women with fetuses of gestational age < 33 weeks whose birth was planned or expected within 24 hours were enrolled from July 1997 to July 2003 with follow up of infants until hospital discharge. METHODS Five hundred and seventy-three mothers were randomly assigned to receive a single 40-ml infusion of 0.1 g/ml of MgSO(4) (4 g) solution or isotonic 0.9% saline (placebo) over 30 minutes. This study is registered as an International Standard Randomised Controlled Trial, number 00120588.\n The primary endpoints were rates of severe WMI or total mortality before hospital discharge, and their combined outcome. Analyses were based on intention to treat.\n After 6 years of enrolment, the trial was stopped. Data from 688 infants were analysed. Comparing infants who received MgSO(4) or placebo, respectively, total mortality (9.4 versus 10.4%; OR: 0.79, 95% CI 0.44-1.44), severe WMI (10.0 versus 11.7%; OR: 0.78, 95% CI 0.47-1.31) and their combined outcomes (16.5 versus 17.9%; OR: 0.86, 95% CI 0.55-1.34) were less frequent for the former, but these differences were not statistically significant. No major maternal adverse effects were observed in the MgSO(4) group.\n Although our results are inconclusive, improvements of neonatal outcome obtained with MgSO(4) are of potential clinical significance. More research is needed to assess the protective effect of MgSO(4) alone or in combination with other neuroprotective molecules.", "Anticonvulsants are used for pre-eclampsia in the belief they prevent eclamptic convulsions, and so improve outcome. Evidence supported magnesium sulphate as the drug to evaluate.\n Eligible women (n=10141) had not given birth or were 24 h or less postpartum; blood pressure of 140/90 mm Hg or more, and proteinuria of 1+ (30 mg/dL) or more; and there was clinical uncertainty about magnesium sulphate. Women were randomised in 33 countries to either magnesium sulphate (n=5071) or placebo (n=5070). Primary outcomes were eclampsia and, for women randomised before delivery, death of the baby. Follow up was until discharge from hospital after delivery. Analyses were by intention to treat.\n Follow-up data were available for 10,110 (99.7%) women, 9992 (99%) of whom received the allocated treatment. 1201 of 4999 (24%) women given magnesium sulphate reported side-effects versus 228 of 4993 (5%) given placebo. Women allocated magnesium sulphate had a 58% lower risk of eclampsia (95% CI 40-71) than those allocated placebo (40, 0.8%, vs 96, 1.9%; 11 fewer women with eclampsia per 1000 women). Maternal mortality was also lower among women allocated magnesium sulphate (relative risk 0.55, 0.26-1.14). For women randomised before delivery, there was no clear difference in the risk of the baby dying (576, 12.7%, vs 558, 12.4%; relative risk 1.02, 99% CI 0.92-1.14). The only notable difference in maternal or neonatal morbidity was for placental abruption (relative risk 0.67, 99% CI 0.45-0.89).\n Magnesium sulphate halves the risk of eclampsia, and probably reduces the risk of maternal death. There do not appear to be substantive harmful effects to mother or baby in the short term.", "Prenatal magnesium sulfate may reduce the risk of cerebral palsy or death in very preterm infants.\n To determine the effectiveness of magnesium sulfate given for neuroprotection to women at risk of preterm birth before 30 weeks' gestation in preventing pediatric mortality and cerebral palsy.\n Randomized controlled trial at 16 tertiary hospitals in Australia and New Zealand with stratification by center and multiple pregnancy. A total of 1062 women with fetuses younger than 30 weeks' gestation for whom birth was planned or expected within 24 hours were enrolled from February 1996 to September 2000 with follow-up of surviving children at a corrected age of 2 years.\n Women were randomly assigned to receive a loading infusion of 8 mL (4 g [16 mmol] of 0.5 g/mL of magnesium sulfate solution or isotonic sodium chloride solution [0.9%]) for 20 minutes followed by a maintenance infusion of 2 mL/h for up to 24 hours.\n Rates of total pediatric mortality, cerebral palsy, and the combined outcome of death or cerebral palsy at a corrected age of 2 years.\n Data were analyzed for 1047 (99%) 2-year survivors. Total pediatric mortality (13.8% vs 17.1%; relative risk [RR], 0.83; 95% confidence interval [CI], 0.64-1.09), cerebral palsy in survivors (6.8% vs 8.2%; RR, 0.83; 95% CI, 0.54-1.27), and combined death or cerebral palsy (19.8% vs 24.0%; RR, 0.83; 95% CI, 0.66-1.03) were less frequent for infants exposed to magnesium sulfate, but none of the differences were statistically significant. Substantial gross motor dysfunction (3.4% vs 6.6%; RR, 0.51; 95% CI, 0.29-0.91) and combined death or substantial gross motor dysfunction (17.0% vs 22.7%; RR, 0.75; 95% CI, 0.59-0.96) were significantly reduced in the magnesium group.\n Magnesium sulfate given to women immediately before very preterm birth may improve important pediatric outcomes. No serious harmful effects were seen.", "To observe the efficacy of magnesium sulfate in the treatment of preterm labor, 65 uncomplicated cases of preterm labor between 28 and 36 weeks of gestation were studied prospectively during Sep. 1988-May 1991. They were divided into two groups randomly. 30 cases were treated with magnesium sulfate and 35 cases with barbiturates or bed rest. The prevention of delivery for at least 48 hours after the initiation of therapy was achieved in 23 of the 30 cases (76.67%) of the magnesium sulfate group and in 3 of the 35 cases (8.57%) in the control group. Delay of more than 7 days was achieved in 17 of the 30 cases (56.67%) and in 2 of the 35 cases (5.71%). The postponement of delivery between the two groups. There was highly significantly difference (P less than 0.01). There was a significant correlation of cervical dilation at the onset of treatment to success of controlling preterm labor. In the magnesium sulfate group, the mean magnesium level to achieve tocolysis was 2.8 +/- 0.35 mmol/L (mean +/- s). The side effects to the mothers, fetus, and the neonates were mild and not prominent.(ABSTRACT TRUNCATED AT 250 WORDS)", "One hundred fifty-six women with preterm labor between 24 and 34 weeks' gestation were randomized to receive either intravenous magnesium sulfate or no tocolytic therapy. Magnesuim sulfate infusions of up to 3 gm/hr were used in 76 pregnancies and resulted in a mean serum magnesium concentration of 5.5 +/- 1.4 mEq/L (mean +/- SEM). Compared with 80 control pregnancies, magnesium sulfate tocolysis had no significant effect on duration of gestation, birth weight, neonatal morbidity, and perinatal mortality. We conclude that clinically safe infusions of magnesium sulfate are ineffective when used to prevent preterm birth.", "Magnesium sulfate has been recommended as a safe and effective agent for inhibiting preterm labor. Its reported adequacy as a tocolytic agent, however, has not been substantiated by randomized, controlled trials. To assess the efficacy of magnesium sulfate, we initiated a prospective, randomized study comparing the capabilities of magnesium sulfate, terbutaline and a placebo (5% dextrose in lactated Ringer's solution) for labor inhibition. The study population consisted of 54 patients between 26 and 34 weeks of gestation and in preterm labor. The diagnosis of labor was made if, following hydration, persistent uterine contractions occurred at a frequency of at least three in a ten-minute period and cervical examination suggested active labor. Success was defined as postponement of delivery for at least 48 hours after initiation of therapy. Despite a trend toward increased efficacy in the terbutaline group there were no significant differences between the three treatment groups with regard to capability of delaying delivery at least 48 hours. Also, there were no significant differences between the groups with regard to gestational age at delivery, birth weight and neonatal survival. The fact that delivery occurred in less than 48 hours of approximately one-half the patients under the best of circumstances emphasizes the need for more effective techniques for the inhibition of preterm labor and the need for a better understanding of the mechanisms involved in the initiation of preterm labor.", "The purpose of this study was to determine whether the use of antenatal magnesium sulfate prevents adverse outcomes (neonatal intraventricular hemorrhage, periventricular leucomalacia, death, and cerebral palsy).\n In a controlled trial, we randomized mothers in preterm labor to magnesium sulfate, \"other\" tocolytic, or placebo. At delivery, umbilical cord blood was collected for the later determination of serum ionized magnesium levels. Neonatal cranial ultrasound scans were obtained periodically for the diagnosis of intraventricular hemorrhage and periventricular leucomalacia. Among survivors, the diagnosis of cerebral palsy was made at age 18 months.\n Children with adverse outcomes had higher umbilical cord magnesium levels at delivery. In regression models that controlled for confounders, which included very low birth weight, magnesium remained a significant risk factor (adjusted odds ratio, 3.7; 95% CI, 1.1-11.9; P =.03).\n Contrary to original hypotheses, this randomized trial found that the use of antenatal magnesium sulfate was associated with worse, not better, perinatal outcome in a dose-response fashion.", "to establish the efficacy and safety of nifedipine and magnesium sulfate in arresting preterm labor.\n seventy-four patients with singleton pregnancies at 23-36 weeks in preterm labor, were selected randomly to receive either oral nifedipine or intravenous magnesium sulfate.\n both drugs had similar tocolytic efficacy and side effects while nifedipine was faster than magnesium sulfate in arresting uterine contractions (4.8 +/- 4.23 vs. 2.98 +/- 3.03 h) P = 0.04.\n this data suggests that oral nifedipine with the same efficacy, side effects and faster action could be a suitable and more convenient alternative to intravenous magnesium sulfate in arresting preterm labor.", "Research suggests that fetal exposure to magnesium sulfate before preterm birth might reduce the risk of cerebral palsy.\n In this multicenter, placebo-controlled, double-blind trial, we randomly assigned women at imminent risk for delivery between 24 and 31 weeks of gestation to receive magnesium sulfate, administered intravenously as a 6-g bolus followed by a constant infusion of 2 g per hour, or matching placebo. The primary outcome was the composite of stillbirth or infant death by 1 year of corrected age or moderate or severe cerebral palsy at or beyond 2 years of corrected age.\n A total of 2241 women underwent randomization. The baseline characteristics were similar in the two groups. Follow-up was achieved for 95.6% of the children. The rate of the primary outcome was not significantly different in the magnesium sulfate group and the placebo group (11.3% and 11.7%, respectively; relative risk, 0.97; 95% confidence interval [CI], 0.77 to 1.23). However, in a prespecified secondary analysis, moderate or severe cerebral palsy occurred significantly less frequently in the magnesium sulfate group (1.9% vs. 3.5%; relative risk, 0.55; 95% CI, 0.32 to 0.95). The risk of death did not differ significantly between the groups (9.5% vs. 8.5%; relative risk, 1.12; 95% CI, 0.85 to 1.47). No woman had a life-threatening event.\n Fetal exposure to magnesium sulfate before anticipated early preterm delivery did not reduce the combined risk of moderate or severe cerebral palsy or death, although the rate of cerebral palsy was reduced among survivors. (ClinicalTrials.gov number, NCT00014989.)\n 2008 Massachusetts Medical Society", "Our purpose was to establish the efficacy and safety of nifedipine versus magnesium sulfate in arresting preterm labor and the efficacy of nifedipine versus terbutaline in preventing recurrent labor.\n Singleton pregnancies at < 34 weeks in preterm labor were randomized to either oral nifedipine or intravenous magnesium sulfate. In case of tocolysis failure ritodrine was added. After labor was arrested, the patients in the nifedipine group were maintained on oral nifedipine, and those in the magnesium sulfate group were treated with oral terbutaline until completing 34 weeks.\n Of 100 patients 80 were considered eligible, of whom 39 were randomized to the nifedipine group. Both groups were comparable in terms of a number of entry variables, including cervical examination, contraction frequency, and gestational age. Both drugs were equally effective in arresting labor and delaying delivery > 48 hours, 92% versus 93%. Both study groups had a similar incidence of side effects, although four (10%) of magnesium sulfate-treated patients required drug discontinuation because of severe symptoms. Nifedipine was as effective as terbutaline in preventing recurrent labor, 26% versus 24%, and in achieving a gestation > 34 weeks, 62% versus 68%.\n Oral nifedipine is as effective as magnesium sulfate and terbutaline in arresting and preventing idiopathic preterm labor.", "In a prospective controlled trial 91 consecutive women with eclampsia were randomly allocated either to a magnesium sulphate and nifedipine regime or to a lytic cocktail and nifedipine group. The type and severity of disease, details of labour and delivery, and the maternal and perinatal outcomes and complications related to the 2 treatment regimens were compared. Recurrence of fits, aspiration pneumonia and sudden hypotension were significantly reduced when patients were treated with the new magnesium sulphate and nifedipine regimen compared with the lytic cocktail plus nifedipine regimen. No patient treated with the new regimen died or had respiratory depression; in the other group there were 2 maternal deaths plus 1 case of severe hypoxic brain damage. No difference was observed in duration of labour or mode of delivery. Perinatal mortality was significantly lower in the magnesium sulphate plus nifedipine treated group. The synergistic action of magnesium sulphate and nifedipine in the dosage employed in this study may be used to reduce maternal and perinatal mortality and morbidity in women with eclampsia.", "To determine whether the administration of prophylactic intravenous magnesium sulphate reduces the occurrence of eclampsia in women with severe pre-eclampsia.\n Randomised controlled trial.\n A tertiary referral obstetric unit.\n Eight hundred and twenty-two women with severe pre-eclampsia requiring termination of pregnancy by induction of labour or caesarean section.\n The women were randomised to receive either placebo (saline) or magnesium sulphate intravenously. The investigators were blinded to the contents of the pre-mixed solutions.\n The occurrence of eclampsia in the two groups.\n The data of 699 women were evaluated. Fourteen were withdrawn after randomisation. The overall incidence of eclampsia was 1.8%. Of 345 women who received magnesium sulphate, one developed eclampsia (0.3%); in the placebo group, 11/340 women (3.2%) developed eclampsia (relative risk 0.09; 95% confidence interval 0.01-0.69; P = 0.003).\n The use of intravenous magnesium sulphate in the management of women with severe pre-eclampsia significantly reduced the development of eclampsia.", "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.", "Magnesium sulfate has been recommended as a safe and effective tocolytic agent. However has not been substantiated by randomized, controlled trials. To assess the efficacy of magnesium sulfate, we initiated prospective randomized study competing the capabilities of magnesium sulfate and terbutaline for labor inhibition. The study population consisted of 30 patients (15 patients with terbutaline and 15 patients with magnesium sulfate) between 28 and 36 weeks of gestation and in preterm labor. One patient in terbutaline group was excluded of the study because we found a severe fetal distress. The diagnosis of labor was made if, persistent uterine contractions occurred at a frequency of at last three in a team-minute period and cervical examination suggested active labor. Success was defined as postponement of delivery for at least 48 hours after initiation of therapy. Despite a trend toward increased efficacy in the terbutaline group (tocolytic Bishop grade and its success) there were no significant differences between the two treatment groups with regard to capability of delaying delivery at least 48 hours. Although there were significant differences for terbutaline regard the tocolysis time. For all these reasons, the efficacy between both groups of treatment is similar, and in a future cases, will be necessary to choose the better agent for every case to study.", "Although magnesium sulfate has been traditional or standard treatment for severe preeclampsia and eclampsia to prevent convulsions, its efficiency has always been in doubt and its induced side-effects also make it controversial for use. In this study, 64 patients, diagnosed with severe preeclampsia, were randomized into group I (34 patients) managed with MgSO4, and group II (30 patients) managed without MgSO4. There were no occurrences of eclampsia in either group. Although there was no statistical significance in the final delivery method, group I had a higher rate in cesarean section, in which most were significantly due to fetal distress (p < 0.05). Furthermore, group I had significantly more babies with poor apgar score than group II (p = 0.019). During the treatment period for those with a gestational age of less than 34 weeks, there were two patients with abruptio placentae in group I and the treatment periods were noted to be longer in group II than in group I. From the results of monitoring serum magnesium level in group I, when therapeutic level was achieved, magnesium sulfate induced great discomfort which might have led to the deterioration of the patients' condition. According to this study, magnesium sulfate's minimal efficiency, and its adverse side-effects, also make magnesium sulfate a poor choice in the management of preeclampsia. Therefore, because of our poor understanding of the etiology of preeclampsia, suitable management should be undertaken without magnesium sulfate. Improvement of the patient's pathophysiological condition or termination of pregnancy as early as possible, is recommended.", "Eclampsia, the occurrence of a seizure in association with pre-eclampsia, remains an important cause of maternal mortality. Although it is standard practice to use an anticonvulsant for management of eclampsia, the choice of agent is controversial and there has been little properly controlled evidence to support any of the options. 1687 women with eclampsia were recruited into an international multicentre randomised trial comparing standard anticonvulsant regimens. Primary measures of outcome were recurrence of convulsions and maternal death. Data are available for 1680 (99.6%) women: 453 allocated magnesium sulphate versus 452 allocated diazepam, and 388 allocated magnesium sulphate versus 387 allocated phenytoin. Most women (99%) received the anticonvulsant that they had been allocated. Women allocated magnesium sulphate had a 52% lower risk of recurrent convulsions (95% CI 64% to 37% reduction) than those allocated diazepam (60 [13.2%] vs 126 [27.9%]; ie, 14.7 [SD 2.6] fewer women with recurrent convulsions per 100 women; 2p < 0.00001). Maternal mortality was non-significantly lower among women allocated magnesium sulphate. There were no significant differences in other measures of serious maternal morbidity, or in perinatal morbidity or mortality. Women allocated magnesium sulphate had a 67% lower risk of recurrent convulsions (95% CI 79% to 47% reduction) than those allocated phenytoin (22 [5.7%] vs 66 [17.1%] ie, 11.4 [SD 2.2] fewer women with recurrent convulsions per 100 women; 2p < 0.00001). Maternal mortality was nonsignificantly lower among women allocated magnesium sulphate. Women allocated magnesium sulphate were also less likely to be ventilated, to develop pneumonia, and to be admitted to intensive care facilities than those allocated phenytoin. The babies of women who had been allocated magnesium sulphate before delivery were significantly less likely to be intubated at the place of delivery, and to be admitted to a special care nursery, than the babies of mothers who had been allocated phenytoin. There is now compelling evidence in favour of magnesium sulphate, rather than diazepam or phenytoin, for the treatment of eclampsia.", "This randomized controlled trial compared the use of magnesium sulphate with diazepam as anticonvulsant in 51 eclamptic women. The use of magnesium sulphate was associated with less serious morbidity (in terms of recurrence of convulsions, cardiopulmonary problems, disseminated intravascular coagulopathy, and acute renal failure) but the difference was not statistically significant (relative risk 0.6; 95% CI 0.3 to 1.2). The one maternal death occurred in the magnesium sulphate group. Convulsions recurred in five (21%) women in the magnesium sulphate group and seven (26%) women in the diazepam group. Urine output poor enough to prompt diuretic stimulation was less frequent in the magnesium sulphate group than in the diazepam group (RR 0.3; 95% CI 0.1 to 0.9). Significantly fewer infants born in the magnesium sulphate group had low Apgar scores (less than 7 at 1 min) compared with those in the diazepam group (RR 0.6; 95% CI 0.4 to 0.9). There were two early neonatal deaths in the magnesium sulphate group, and three stillbirths in the diazepam group. This study suggests that magnesium sulphate has advantages over diazepam for the mother and the infant in the treatment of eclampsia, but the trial is small and should be replicated on a larger scale.", "The aim of this study was to compare the efficacy and safety of oral nicardipine in acute therapy for preterm labor with those of parenteral magnesium sulfate.\n Patients between 24 and 34 weeks' gestation with documented preterm labor were randomly assigned to receive oral nicardipine (n = 57) or intravenous magnesium sulfate (n = 65) as initial tocolytic therapy. Patients in the nicardipine group received a 40-mg loading dose and then 20 mg every 2 hours as needed to stop contractions (total 80 mg). Patients in the magnesium sulfate group received a 6-g bolus followed by 2 to 4 g/h to provide uterine quiescence. Patients could be switched to another tocolytic regimen if they continued to have contractions after 6 hours of therapy. The main outcome variables examined were time to uterine quiescence, time gained in utero, recurrence of preterm labor, failure of tocolysis, and pertinent maternal and neonatal outcomes.\n There were no significant differences in maternal demographic characteristics between the groups. Among patients who responded with uterine quiescence within 6 hours, there was a significant decrease in the time to uterine quiescence in the nicardipine group (P <.01). Patients in the magnesium sulfate group were more likely to have recurrence of preterm labor necessitating further tocolytic attempts (P =.048). The patients in the magnesium sulfate group had more adverse side effects, mainly nausea and vomiting (P =.004). There were no differences in birth weight, estimated gestational age at delivery, or neonatal complications between the 2 groups.\n Oral nicardipine is an effective, safe, and well-tolerated tocolytic agent. In this prospective clinical trial patients randomly assigned to receive oral nicardipine had arrest of preterm labor more rapidly than did those randomly assigned to receive parenteral magnesium sulfate. Patients who received magnesium sulfate were more likely to have adverse medication effects and recurrent preterm labor.", "Ritodrine, terbutaline, and magnesium sulfate have all been used in the United States as tocolytic drugs. Studies have shown each of these drugs to be effective in suppressing preterm labor. The current study was undertaken in order to compare their relative safety and efficacy and to evaluate the effectiveness of a second drug when the first-used drug failed to stop contractions. No differences in efficacy could be demonstrated between the drugs; however, there was a marked difference in the incidence of maternal side effects. Because of an unacceptable level of side effects, we have stopped the use of terbutaline at our institution.", "Patients with severe pre-eclampsia were randomised to receive magnesium sulphate according to an intramuscular (IM) (N = 9) or an intravenous (i.v.) (N = 8) regimen. The IM regimen consisted of a loading dose of 14 g (4 g i.v. and 10 g IM) followed by 5 g 4-hourly. Patients given the IV regimen received a 6 g i.v. loading dose followed by a maintenance infusion of 2 g/h. Clinical outcome, laboratory parameters and serum magnesium levels were recorded for both groups. There were no significant differences between groups with regard to clinical outcome of either mother or child. Similar average serum magnesium concentrations were produced by the regimens the only significant difference was that fluctuations in magnesium levels were greater with the IM than the i.v. regimen. None of the patients had seizures despite levels mostly below 2 mmol/l." ]	Magnesium sulphate is ineffective at delaying birth or preventing preterm birth, and its use is associated with an increased mortality for the infant. Any further trials should be of high quality, large enough to assess serious morbidity and mortality, compare different dose regimens, and provide neurodevelopmental status of the child.
CD005941	[ "15815217", "18472878", "2240110" ]	[ "Probiotics affects vaginal flora in pregnant women, suggesting the possibility of preventing preterm labor.", "Randomized trial of antibiotics in addition to tocolytic therapy to treat preterm labor.", "Cervicovaginal microflora and pregnancy outcome: results of a double-blind, placebo-controlled trial of erythromycin treatment." ]	[ "nan", "The objective of this study was to assess whether antibiotic therapy plus tocolysis given to women in preterm labor would prolong pregnancy compared with tocolysis alone.\n A randomized, double-blind trial of intravenous mezlocillin and oral erythromycin therapy vs. placebo was used in addition to tocolysis among women in preterm labor < or =34 weeks gestation with intact membranes. Amniocentesis was performed, and chorioamnionic membranes were examined histologically and cultured for microorganisms after delivery.\n Clinical characteristics including gestational age at enrollment, frequency of contractions, cervical Bishop's score, and white blood cell count on admission were similar in the 2 groups. Antibiotic therapy was well tolerated. No significant differences in the interval to delivery, birth weight, and neonatal outcomes were observed between the 2 groups. Women in the antibiotic group had a significantly lower incidence of postpartum infections compared with women in the placebo group. Patients with evidence of upper genital tract infection in either group had a significantly shorter interval to delivery, lower gestational age at delivery, lower mean birth weight, and increased neonatal hospitalization time.\n Lack of an antibiotic effect on the gestational age at delivery may be due to the low prevalence of upper genital tract infection among unselected women in preterm labor, to advanced preterm labor unresponsive to antibiotic therapy, or to an inability of antibiotics given alone to inhibit the cytokine response. Further work is needed to identify markers of upper genital tract infection among women in preterm labor and to evaluate other potential therapeutic interventions.", "Available information suggests that some instances of preterm birth or premature rupture of membranes are associated with clinically unrecognized infection and inflammation of the lower uterine segment, decidua, and fetal membranes. Various cervicovaginal microorganisms have been recovered from these sites. Many of these microorganisms produce factors that may lead to weakening of the fetal membranes, release of prostaglandins, or both. This study evaluated the presence of various lower genital tract microflora and bacterial conditions in 229 women enrolled in a double-blind, placebo-controlled trial of short-course erythromycin treatment at 26 to 30 weeks' gestation to prevent preterm birth. Demographic, obstetric, and microbiologic parameters were prospectively evaluated. Premature rupture of membranes occurred less frequently (p less than 0.01) among women who received erythromycin (6%) versus placebo (16%). Preterm premature rupture of membranes also occurred less frequently, although not significantly (p = 0.3) in patients who received erythromycin (2%) versus placebo (5%). Erythromycin treatment significantly decreased the occurrence of premature rupture of membranes among women who were initially positive for Chlamydia trachomatis infection. Logistic regression analysis demonstrated that C. trachomatis (p = 0.05; odds ratio, 9), vaginal wash phospholipase C (p = 0.08; odds ratio, 6) and prior preterm birth (p = 0.007; odds ratio 17) were associated with increased risk of preterm birth. Bacterial vaginosis, Mycoplasma hominis, Ureaplasma urealyticum were not significantly associated with increased risk of preterm birth or preterm rupture of membranes. These findings support a role for selected lower genital tract microflora in preterm birth and premature rupture. Large controlled treatment trials of specific infections or conditions associated with preterm birth and premature rupture of membranes are required to confirm the value of antimicrobial treatments in prevention of microbial-associated preterm birth." ]	Although the use of probiotics appears to treat vaginal infections in pregnancy, there are currently insufficient data from trials to demonstrate any impact on preterm birth and its complications.
CD003769	[ "20538079", "16930145", "15570201", "14505238", "15737849", "1448739", "11141221", "18453491", "21259031", "9327671", "16860624", "6851752", "2403655", "10873356" ]	[ "Prophylactic antibiotics in open mesh repair of inguinal hernia - a randomized controlled trial.", "The role of antibiotic prophylaxis in elective tension-free mesh inguinal hernia repair: results of a single-centre prospective randomised trial.", "The role of antibiotic prophylaxis in prevention of wound infection after Lichtenstein open mesh repair of primary inguinal hernia: a multicenter double-blind randomized controlled trial.", "The role of antibiotic prophylaxis on wound infection after mesh hernia repair under local anesthesia on an ambulatory basis.", "A randomized, double-blind, placebo-controlled trial to determine effectiveness of antibiotic prophylaxis for tension-free mesh herniorrhaphy.", "Local antibiotic prophylaxis in inguinal hernia repair.", "Effect of single-dose prophylactic ampicillin and sulbactam on wound infection after tension-free inguinal hernia repair with polypropylene mesh: the randomized, double-blind, prospective trial.", "The role of antibiotic prophylaxis in mesh repair of primary inguinal hernias using prolene hernia system: a randomized prospective double-blind control trial.", "Prospective randomized evaluation of prophylactic antibiotic usage in patients undergoing tension free inguinal hernioplasty.", "Antibiotic prophylaxis and open groin hernia repair.", "Predictive risk score for infection after inguinal hernia repair.", "[Infection prevention in elective large intestine surgery. Results of a prospective randomized comparative study].", "Perioperative antibiotic prophylaxis for herniorrhaphy and breast surgery.", "Antibiotic prophylaxis for post-operative wound infection in clean elective breast surgery." ]	[ "The role of prophylactic antibiotics in mesh repair of inguinal hernia is unclear. A Cochrane meta-analysis in 2005 concluded that \"antibiotic prophylaxis for elective inguinal hernia repair cannot be firmly recommended or discarded\" and \"further studies are needed, particularly on the use for mesh repair.\" So, we designed a study to define the role of prophylactic antibiotics in mesh repair of inguinal hernia. We conducted a prospective, randomized, double-blind, trial comparing wound infection rates in 450 patients (225 received intravenous Cefazolin, 225 received a placebo) undergoing primary inguinal hernia repair electively using polypropylene mesh. 334 patients who completed a followup period of one month were analyzed. Age, American Society of Anesthesiologists class, type of hernia, type of anesthesia, grade of surgeon, pre and postoperative hospital stay and duration of operation were recorded. CDC criteria was used to define wound infection. Groups were well matched for all preoperative variables studied. The overall infection rate was 8.7% (29 out of 334). The incidence of wound infection in antibiotic group was 7% and 10.5% in control group. One from each group developed deep surgical site infection. Most of the infections occurred between the 7th and 12th post-operative day after discharge from the hospital. Antibiotic prophylaxis was associated with decreased incidence of wound infection when compared to control group, but the difference was not statistically significant. Based on our results we do not recommend the routine use of antibiotic prophylaxis in elective mesh repair of inguinal hernias.\n Copyright © 2010 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.", "Hernia repair is one of the so-called clean operations. Many surgeons, however, use antibiotics, especially in the mesh repair era, without strong evidence to support this policy. We conducted a single-centre prospective randomised trial with a view to clarify this issue on a scientific basis. From January 2000 all patients undergoing elective inguinal hernia repair using a tension-free polypropylene mesh technique, provided they fulfilled predetermined criteria, were randomised to have a single dose of amoxicillin and clavoulanic acid or placebo in a double-blind manner. The main end point was to detect any difference in infectious complication rates - with specific interest to wound infection rates - between the two groups. Between January 2000 and June 2004, 386 patients entered the study (364 men and 22 women, median age 63 years, range 15-90 years) and were randomised to have antibiotic prophylaxis (group A, n = 193) or placebo (group B, n = 193). The two groups were comparable regarding demographic data. In total, 19 (5%) cases with infectious complications were detected. Fourteen of these were wound infections (3.7%). There were five cases of wound infection in group A and nine in group B (p = 0.4, Fisher's exact test). All wound infections were treated with antibiotics. The wound was opened in some cases. Mesh removal was not required in any of the cases. From the results of this study it does not appear that antibiotic prophylaxis offers any benefits in the elective mesh inguinal hernia repair.", "To determine whether the use of prophylactic antibiotics is effective in the prevention of postoperative wound infection after Lichtenstein open mesh inguinal hernia repair.\n A recent Cochrane meta-analysis (2003) concluded that \"antibiotic prophylaxis for elective inguinal hernia repair cannot be firmly recommended or discarded.\"\n Patients with a primary inguinal hernia scheduled for Lichtenstein repair were randomized to a preoperative single dose of 1.5 g intravenous cephalosporin or a placebo. Patients with recurrent hernias, immunosuppressive diseases, or allergies for the given antibiotic were excluded. Infection was defined using the Centers for Disease Control and Prevention criteria.\n We included 1040 patients in the study between November 1998 and May 2003. According to the intention-to-treat principle, 1008 patients were analyzed. There were 8 infections (1.6%) in the antibiotic prophylaxis group and 9 (1.8%) in the placebo group (P = 0.82). There was 1 deep infection in the antibiotic prophylaxis group and 2 in the placebo group (P = 0.57). Statistical analysis showed an absolute risk reduction of 0.19% (95% confidence interval, -1.78%-1.40%) and a number needed to treat of 520 for the total number of infections. For deep infection, the absolute risk reduction is 0.20% (95% confidence interval, -0.87%-0.48%) with a number needed to treat of 508.\n A low percentage (1.7%) of wound infection after Lichtenstein open mesh inguinal (primary) hernia repair was found, and there was no difference between the antibiotic prophylaxis or placebo group. The results show that, in Lichtenstein inguinal primary hernia repair, antibiotic prophylaxis is not indicated in low-risk patients.", "Mesh prosthesis, local anesthesia, and ambulatory care have been widely introduced in recent decades in the treatment of inguinal hernia. The use of antibiotic prophylaxis during open inguinal hernia repair has been controversial. No prospective trial has been conducted to assess the role of antibiotic prophylaxis in patients operated on for inguinal hernia under the above-mentioned conditions. A prospective, randomized, double-blinded trial was initiated to assess the efficacy of antibiotic prophylaxis in the prevention of wound infection during open mesh inguinal hernia repair under local anesthesia on an ambulatory basis. Ninety-nine consecutive hernia repairs were randomized to receive 1 g of parenteral Cefazolin preoperatively or a placebo. No wound infections existed in the therapeutic group (0/50). Four infections appeared in the control group (4/49), and the study was suspended for ethical reasons when differences reached values close to statistical significance ( P=0.059). We conclude that a single dose of intravenous Cefazolin decreases the risk of wound infection during open mesh inguinal hernia repair under local anesthesia on an ambulatory basis.", "In recent years, use of prosthetic material for inguinal hernia repair has increased dramatically. Tension-free repairs have gained popularity not only for recurrent or complicated hernias, but for primary hernia repairs as well. Although routine use of prophylactic antibiotics is not recommended in the Philippines for open nonimplant herniorrhaphy, there is little direct clinical evidence on which to base recommendations when implantable mesh is used.\n We conducted a prospective, randomized, double-blind, placebo-controlled trial comparing wound infection rates in 360 patients (180 received prophylactic antibiotics, 180 received a placebo) undergoing primary inguinal hernia repair electively using polypropylene mesh. Age, gender, American Society of Anesthesiologists class, type of hernia, type of anesthesia, and duration of operation were recorded. Infections were evaluated 1 week, 2 weeks, and 1 month after operation by an independent surgeon. All complications were recorded. Results were assessed using chi-square, Fisher's exact test, and Student's t-tests as appropriate.\n Groups were well matched for all preoperative variables studied, including comorbid conditions. Six patients from the antibiotic group and four from the placebo group failed to followup after the second week. Superficial surgical site infection developed in 3 patients (1.7%) from the antibiotic group and 6 (3.3%) from the placebo group (p = 0.50). One from each group developed deep surgical site infection. Both patients were readmitted and underwent repeated debridement, which eventually resulted in graft loss.\n Preoperative administration of single-dose antibiotic for tension-free inguinal mesh herniorrhaphy did not markedly decrease risk of wound infection in this patient population. Our results do not support use of antibiotic prophylaxis for tension-free mesh herniorrhaphy.", "We compared the effects of single dose (750 milligrams) prophylactic cefamandole delivered directly into the operative wound with local anesthesia (n = 162) with a control group (no antibiotics) (n = 162) in a randomized trial. No adverse effects were observed. There were seven wound abscesses in the untreated group compared with none in the group receiving antibiotic prophylaxis (p = 0.007). Six of the seven abscesses occurred as late as one month after the patient was discharged from the hospital. The costs of antibiotics used were ten times less than the costs of treatment of wound complications in the control group.", "To assess the value of single-dose, intravenous, prophylactic ampicillin and sulbactam (AS) in the prevention of wound infections during open prosthetic inguinal hernia repair by a double-blind, prospective, randomized trial.\n The use of antibiotic prophylaxis during open prosthetic inguinal hernia surgery is controversial, and no prospective trial has been conducted to examine this issue.\n Patients undergoing unilateral, primary inguinal hernia repair electively with the Lichtenstein technique using polypropylene mesh were randomized to receive 1.5 g intravenous AS before the incision or an equal volume of placebo according to a predetermined code of which the surgeons were unaware. Patients with recurrent, femoral, bilateral, giant, or incarcerated hernias or any systemic diseases were excluded. Age, sex, body mass index, American Society of Anesthesiologists score, type of hernia, type of anesthesia, duration of surgery, and use of drains were recorded. Infection was defined according to the criteria of Centers for Disease Control. Patients were evaluated 1 week, 1 month, 6 months, and 1 year after surgery by an independent surgeon. All complications were recorded. Results were assessed using chi-square, Fisher's exact, and Student t tests as appropriate.\n Between September 1996 and July 1998, 280 patients (140 AS, 140 placebo group) entered the protocol. Four patients from the AS group and seven from the placebo group were excluded because of inadvertent antibiotic administration or follow-up problems. Groups were well matched for all the variables studied and postoperative complications, excluding wound infections, which occurred at a rate of 0.7% in the AS group and 9% in the placebo group (P =.00153). Twelve patients in the placebo group developed wound infections, requiring five repeat hospital admissions in three patients. These three patients suffered deep infections reaching the graft, which resulted in graft loss in two. The single infected patient in the AS group had his graft removed as well because of deep persistent infection.\n This study documented a significant (10-fold) decrease in overall wound infections when single-dose, intravenous AS was used during Lichtenstein hernia repair. Deep infections and wound infection-related readmissions were also reduced by the use of AS. Proponents of mesh repairs may therefore be advised to use prophylactic single-dose intravenous antibiotic coverage in the light of the results of this trial. AS proved to be an effective antimicrobial agent.", "Antibiotic prophylaxis is being commonly used in mesh repair of inguinal hernia but its role has been questioned in a recent Cochrane analysis performed in 2003. Routine use of antibiotic prophylaxis in mesh repair of inguinal hernia can lead to bacterial resistance and increase in cost. In a present double-blind placebo controlled trial involving 120 patients undergoing inguinal hernia repair using prolene hernia system, we did not find any benefit of the routine use of antibiotic prophylaxis in terms of wound infection rate.", "Assessment of the usefulness of antibiotic prophylaxis in inguinal hernioplasty.\n This prospective randomized double blind study was conducted on 98 patients. Group A (50 patients) received a single dose of intravenous amoxicillin and clavulanic acid, and Group P (48 patients) received an equal volume of normal saline placebo by intravenous bolus 30 min before the induction of anesthesia. Hernioplasty was performed with polypropylene mesh. Skin was closed using skin staples that were removed after complete wound healing. The surgical site infection was diagnosed according to APIC, CDC criteria ( http://www.apic.org ).\n The mean operative time was 38.8 ± 10.8 min in group A versus 40.9 ± 11.1 min in group P (P = 0.34). The mean hospitalization time was 1.3 ± 0.463 days in group A versus 1.25 ± 0.438 days in group P (P = 0.58). Four patients (2%) in group A and 6 patients (2.88%) in group P had wound infections (P = 0.47). Group A had 3 superficial infections and 1 deep infection while group P had 5 superficial infections and 1 deep infection. Antibiotic treatment of the wound infection was successful in all patients. Wound culture showed Staphylococcus aureus infection in 1 patient each group, Streptococcus pyogenes in 1 group A patient and Pseudomonas aeruginosa in 1 group P patient. Cultures in other patients in both groups were reported to be sterile.\n Prophylactic antibiotic usage in patients undergoing tension free inguinal hernioplasty did not show any statistically significant beneficial effects in reduction of surgical site infection.", "Antibiotic prophylaxis is not routinely given for nonimplant, clean operations, although this view has recently been challenged. We have conducted a randomized multicenter, double-blind prospective trial to compare co-amoxiclav with placebo in 619 patients undergoing open groin hernia repair. Altogether 563 (91%) patients fulfilled the protocol; 283 received co-amoxiclav and 280 placebo. There was no difference between the groups in the number of patients receiving local or general anesthetic, the type of repair performed, the use of a subcutaneous fat suture, the type of skin closure used, the use of wound analgesia, or the use of a wound drain. Patients were given a card to return to the hospital in the event of their wound discharging or their needing to see their general practitioner. All patients were reviewed at approximately 6 weeks after operation. Fifty (8.9%) patients sustained a wound infection, 25 in the co-amoxiclav group and 25 in the placebo group. We conclude that antibiotic prophylaxis is of no benefit to patients undergoing open groin hernia repair.", "Identification of subgroups of patients at high and low risk for global infectious complications (GIC) after inguinal hernia repair without mesh.\n A database of 1254 patients who underwent inguinal hernia repair without mesh, issued from 3 prospective multicenter randomized trials, has been established (group A). After multivariate analysis, a score for GIC was calculated and tested using data from a similar prospective randomized multicenter study (group B).\n A risk score for GIC was constructed: -4.7 + (0.95 x age > or =75 years) + (1.1 obesity) + (2.1 x urinary catheter). In case of score less than -4.2 (low-risk group), the GIC rate was 2.7%; therefore, in case of score more than -4.2 (high-risk score), the GIC rate was 14.3% (P < .001). In the low-risk group, the administration of antibiotic prophylaxis did not reduce the infectious complication rate, while in high-risk group the administration of antibiotic prophylaxis significantly reduced the rates of surgical site infection, GIC, and urinary infection by 72%, 67%, and 76.8%, respectively.\n This study demonstrates the efficacy of antibiotic prophylaxis in inguinal hernia surgery in the subgroup of high-risk patients.", "In a prospective randomized trial clinical results of orthograde bowel lavage alone (group I) versus combined bowel lavage and parenteral antibiotic prophylaxis with 4 gm Cefoxitin (group II) in two separate dosages (perioperative short-term-prophylaxis) are compared with regard to the reduction of septic complications after colorectal surgery. Septic wound complications were 11/27 = 41% in group I and 2/30 = 7% in group II. The rate of anastomotic leakages was significantly different in the two groups (5/27 in group I, 0 in group II). The monetary costs for given antibiotics and the duration of hospitalization were less in group II. Orthograde bowel lavage alone proved to be of no effect in reducing the rate of septic complications when used without antibiotic perioperative short-term-prophylaxis and therefore cannot be recommended to be used solely.", "We assessed the efficacy of perioperative antibiotic prophylaxis for surgery in a randomized, double-blind trial of 1218 patients undergoing herniorrhaphy or surgery involving the breast, including excision of a breast mass, mastectomy, reduction mammoplasty, and axillary-node dissection. The prophylactic regimen was a single dose of cefonicid (1 g intravenously) administered approximately half an hour before surgery. The patients were followed up for four to six weeks after surgery. Blinding was maintained until the last patient completed the follow-up and all diagnoses of infection had been made. The patients who received prophylaxis had 48 percent fewer probable or definite infections than those who did not (Mantel-Haenszel risk ratio, 0.52; 95 percent confidence interval, 0.32 to 0.84; P = 0.01). For patients undergoing a procedure involving the breast, infection occurred in 6.6 percent of the cefonicid recipients (20 of 303) and 12.2 percent of the placebo recipients (37 of 303); for those undergoing herniorrhaphy, infection occurred in 2.3 percent of the cefonicid recipients (7 of 301) and 4.2 percent of the placebo recipients (13 of 311). There were comparable reductions in the numbers of definite wound infections (Mantel-Haenszel risk ratio, 0.49), wounds that drained pus (risk ratio, 0.43), Staphylococcus aureus wound isolates (risk ratio, 0.49), and urinary tract infections (risk ratio, 0.40). There were also comparable reductions in the need for postoperative antibiotic therapy, non-routine visits to a physician for problems involving wound healing, incision and drainage procedures, and readmission because of problems with wound healing. We conclude that perioperative antibiotic prophylaxis with cefonicid is useful for herniorrhaphy and certain types of breast surgery.", "Antibiotic prophylaxis has been used to good effect in the prevention of post-operative wound infections in patients undergoing gastrointestinal operations. We have assessed the use of a single dose of intravenous antibiotic (Augmentin 1.2 g), given with induction of anaesthesia as prophylaxis, against post-operative wound infection in women undergoing clean, elective breast surgery. Three hundred and thirty-four patients were recruited. Of the 164 receiving antibiotic prophylaxis 29 (17.7%) had wound infections compared with 32 (18.8%) in the placebo group (P=0.79). There were no significant differences in any other post-operative infective complications. Antibiotic prophylaxis is probably not required in clean, elective breast surgery.\n Copyright 2000 Harcourt Publishers Ltd." ]	Based on the results of this systematic review the administration of antibiotic prophylaxis for elective inguinal hernia repair cannot be universally recommended. Neither can the administration be recommended against when high rates of wound infection are observed.
CD004733	[ "2223677", "20233384", "8238130", "10428520", "3046651", "12745558" ]	[ "Failure to prevent preterm labour and delivery in twin pregnancy using prophylactic oral salbutamol.", "Global report on preterm birth and stillbirth (3 of 7): evidence for effectiveness of interventions.", "Antibiotic treatment of preterm labor with intact membranes: a multicenter, randomized, double-blinded, placebo-controlled trial.", "Prophylactic administration of clindamycin 2% vaginal cream to reduce the incidence of spontaneous preterm birth in women with an increased recurrence risk: a randomised placebo-controlled double-blind trial.", "A double-blind randomized controlled trial on the use of prophylactic antibiotics in patients undergoing elective caesarean section.", "A randomised, double-blind placebo-controlled trial of ascorbic acid supplementation for the prevention of preterm labour." ]	[ "A double blind, controlled study was performed to see whether the use of prophylactic oral salbutamol would reduce the incidence of preterm labour in twin pregnancy. Of the 144 women studied, 74 took salbutamol and 70 placebo. No difference was found in the length of gestation, birthweight or fetal outcome, although fewer babies suffered from respiratory distress syndrome in the salbutamol group. Women did not experience troublesome side-effects from salbutamol.", "Interventions directed toward mothers before and during pregnancy and childbirth may help reduce preterm births and stillbirths. Survival of preterm newborns may also be improved with interventions given during these times or soon after birth. This comprehensive review assesses existing interventions for low- and middle-income countries (LMICs).\n Approximately 2,000 intervention studies were systematically evaluated through December 31, 2008. They addressed preterm birth or low birth weight; stillbirth or perinatal mortality; and management of preterm newborns. Out of 82 identified interventions, 49 were relevant to LMICs and had reasonable amounts of evidence, and therefore selected for in-depth reviews. Each was classified and assessed by the quality of available evidence and its potential to treat or prevent preterm birth and stillbirth. Impacts on other maternal, fetal, newborn or child health outcomes were also considered. Assessments were based on an adaptation of the Grades of Recommendation Assessment, Development and Evaluation criteria.\n Most interventions require additional research to improve the quality of evidence. Others had little evidence of benefit and should be discontinued. The following are supported by moderate- to high-quality evidence and strongly recommended for LMICs: Two interventions prevent preterm births--smoking cessation and progesterone. Eight interventions prevent stillbirths--balanced protein energy supplementation, screening and treatment of syphilis, intermittant presumptive treatment for malaria during pregnancy, insecticide-treated mosquito nets, birth preparedness, emergency obstetric care, cesarean section for breech presentation, and elective induction for post-term delivery. Eleven interventions improve survival of preterm newborns--prophylactic steroids in preterm labor, antibiotics for PROM, vitamin K supplementation at delivery, case management of neonatal sepsis and pneumonia, delayed cord clamping, room air (vs. 100% oxygen) for resuscitation, hospital-based kangaroo mother care, early breastfeeding, thermal care, and surfactant therapy and application of continued distending pressure to the lungs for respiratory distress syndrome\n The research paradigm for discovery science and intervention development must be balanced to address prevention as well as improve morbidity and mortality in all settings. This review also reveals significant gaps in current knowledge of interventions spanning the continuum of maternal and fetal outcomes, and the critical need to generate further high-quality evidence for promising interventions.", "Although an association between subclinical intrauterine infection and preterm birth is well established, there is conflicting evidence regarding the benefits of antibiotic administration to women in preterm labor with intact membranes. We attempted to determine the effect of ampicillin-amoxicillin and erythromycin treatment on prolongation of pregnancy, the rate of preterm birth, and neonatal morbidity in patients with preterm labor and intact membranes.\n A multicenter, randomized, double-blinded, placebo-controlled trial was designed and implemented by the Maternal-Fetal Medicine Units Network of the National Institute of Child Health and Human Development. Two hundred seventy-seven women with singleton pregnancies and preterm labor with intact membranes (24 to 34 weeks) were randomly allocated to receive either antibiotics or placebos.\n Of the 2373 patients screened for participation in this study in six medical centers, 277 women were enrolled (n = 133 for antibiotics group vs n = 144 for placebo group). In each study group, 60% of patients completed all the study medications. The overall prevalence of microbial invasion of the amniotic cavity was 5.8% (14/239). No significant difference between the antibiotic group and the placebo group was found in maternal outcomes, including duration of randomization-to-delivery interval, frequency of preterm delivery (< 37 weeks), frequency of preterm premature rupture of membranes, clinical chorioamnionitis, endometritis, and number of subsequent admissions for preterm labor. Similarly, no significant difference in neonatal outcomes could be detected between the two groups including respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, sepsis, and admission and duration of newborn intensive special care unit hospitalization.\n The results of this study do not support the routine use of antibiotic administration to women in preterm labor with intact membranes.", "To test the hypothesis that prophylactic administration of clindamycin 2% vaginal cream can reduce the incidence of preterm birth in a high risk population.\n A multi-centre, randomised, double-blind, placebo-controlled trial.\n Twelve city hospitals in The Netherlands.\n One hundred and sixty-eight women with a singleton pregnancy and a history of a spontaneous preterm delivery in the preceding pregnancy.\n Clindamycin 2% vaginal cream, or placebo cream, administered daily for seven days at 26 and 32 weeks of gestation.\n Spontaneous preterm birth at < 37 weeks, admission for threatened preterm labour, neonatal infectious morbidity.\n In the intention-to-treat analysis no difference was found in overall preterm birth between clindamycin and placebo (23% vs 18%, respectively). In the subgroup who completed the trial and administered all medication, more women delivered before 34 weeks in the clindamycin group (1.4% in the placebo vs 9.0% in the clindamycin group; P < 0.05). The length of admissions for threatened preterm labour did not differ. More infectious neonatal morbidity was seen in the clindamycin group (5/83 vs 0/85; P < 0.05).\n Clindamycin 2% vaginal cream given prophylactically to women with a spontaneous preterm birth in the preceding pregnancy did not prevent preterm delivery or reduce the number of admissions for threatened preterm labour. The neonatal infectious morbidity in the group treated with clindamycin was significantly higher and a major concern.", "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.", "In a previous study from this institution, patients at high risk for preterm labour were screened for the presence of bacterial vaginosis (BV). When BV was present, they were randomised to receive either treatment (metronidazole) or placebo (vitamin C). There were significantly more patients with preterm labour in the metronidazole group. The aim of this double-blind randomised placebo-controlled trial study was to determine whether vitamin C could indeed reduce the recurrence risk of preterm labour. Patients with a history of preterm labour in a preceding pregnancy were randomised to receive 250 mg vitamin C or a matching placebo twice daily until 34 weeks' gestation. They attended a dedicated premature labour clinic. Significantly more women delivered before term in the group that received vitamin C, but there was no difference in the outcome of the babies between the two groups. Supplementation with vitamin C did not prevent premature labour." ]	There is insufficient evidence to support or refute the use of prophylactic oral betamimetics for preventing preterm birth in women with a twin pregnancy.
CD006176	[ "8775240", "3555083", "3300348", "9501783", "7657008", "9737127", "1709781" ]	[ "The effect of intraumbilical oxytocin on the third stage of labour.", "The effect of oxytocin injection into the umbilical vein for the management of the retained placenta.", "Influence of umbilical vein administration of oxytocin on the third stage of labor: a randomized, double-blind, placebo-controlled study.", "Intra-umbilical vein injection and retained placenta: evidence from a collaborative large randomised controlled trial. Grupo Argentino de Estudio de Placenta Retenida.", "Hyponatraemia and non-electrolyte solutions in labouring primigravida.", "Effect of umbilical vein oxytocin injection on the third stage of labor: a randomized controlled study.", "Umbilical vein administration of oxytocin for the management of retained placenta: is it effective?" ]	[ "The umbilical vein administration of oxytocin in saline was compared with umbilical vein saline alone and the traditional management of the third stage of labour. Seventy-two women were randomized to 3 groups. Group 1 received intraumbilical 20 IU of oxytocin diluted to 40 mL with saline. Group 2 received intraumbilical vein 40 mL of saline while subjects in group 3 were managed according to the standard protocol without any intraumbilical injection. No significant differences were found in terms of the length of the third stage, the blood loss in the third stage and postpartum haematocrit differences among the 3 groups. The administration of diluted oxytocin or saline do not seem to have any superiority to the traditional management of the third stage of labour.", "In a single-blind study 51 patients with retention of the placenta were randomized into one of three groups: Group 1 was given 10 IU of oxytocin in 10 ml of sodium chloride into the umbilical vein; group 2 was given 10 ml of sodium chloride; group 3 was treated with manual removal of the placenta. No significant differences were recorded in groups 1 and 2, and no advantages were found in comparison with the procedure normally used.", "A randomized, double-blind, placebo-controlled study evaluated the influence of umbilical vein administration of oxytocin on the third stage of labor. Five minutes after delivery, 37 women received 10 units of oxytocin diluted in physiologic saline solution to a total volume of 20 ml; 41 women received 20 ml of saline solution alone. There was no significant difference between groups in mean (+/- SD) injection-placental expulsion interval (9 +/- 7 versus 10 +/- 8 minutes).", "To determine whether intra-umbilical vein injection with saline solution, with or without oxytocin, reduces the need for manual removal of placenta compared with expectant management.\n Multicenter, randomised controlled trial.\n Eleven hospitals in four cities of Argentina: Buenos Aires, Corrientes, Rosario, and Salta.\n Two hundred and ninety-one women showing no evidence of placental separation thirty minutes after vaginal delivery.\n Three different management strategies: 1. intra-umbilical vein injection of saline solution plus oxytocin; 2. intra-umbilical vein injection of saline solution alone; and 3. expectant management.\n Primary: manual removal of the placenta. Secondary: blood loss after trial entry, haemoglobin level at 24 to 48 hours and at 40 to 45 days after delivery, blood transfusion, curettage, infection, and days of hospital stay.\n Rates of subsequent manual removal were similar: intra-umbilical vein injection of saline solution plus oxytocin (58%; RR 0.92; 95% CI 0.73-1.15), or saline alone (63%; RR 1.00; 95% CI 0.80-1.24), compared with expectant management (63%). There were also no detectable effects of the active managements on any of the secondary measures of outcome.\n Based on evidence available from randomised controlled trials, including this trial, it is unlikely that intra-umbilical injection with or without oxytocin, is clinically useful. We recommend that this intervention should not be used in third stage management of labour.", "We performed a prospective randomised study on one hundred primigravid women who required oxytocin to augment labour, comparing dextrose infusion with normal saline. After delivery, the 45 patients whose oxytocin was infused in dextrose had significantly lower serum sodium levels in both mother and baby compared to the 48 patients who had their oxytocin administered in normal saline. This was particularly evident in those cases where epidural analgesia was employed.", "To evaluate the effect of umbilical vein oxytocin injection on the duration of third stage of labor, and estimated blood loss within 24 hours postpartum, in 50 vaginal parturients at Rajavithi Hospital from March 1, 1994 and June 30, 1995. The parturients were randomized to administered either an umbilical vein injection of 20 units of oxytocin diluted to 20 ml with normal saline (oxytocin group) or only normal saline 20 ml (control group) immediately after cord clamping. There were 25 paturients in each group. The duration of the third stage of labor in the oxytocin group was significantly shorter than that in the control group. In only 1 case of the control group was manual placental removal performed. The estimated blood loss within 24 hours postpartum in both groups was not statistically different. Twenty units of umbilical vein oxytocin injection was effective to shorten the duration of the third stage of labor but were not effective to reduce the estimated blood loss within 24 hours postpartum. The need for a further large scale study in the future was suggested.", "In a multicenter randomized controlled trial involving 220 women with retained placenta no beneficial effects could be established of intraumbilical vein administration of 10 IU of oxytocin in 20 ml of saline solution. A reduction was not gained in the rate of manual removal of the placenta and there was no decrease in the amount of blood loss. Oxytocin only induced a minor shortening of the median time interval from administration to the spontaneous expulsion of the placenta as compared with a placebo injection. Maternal serum alpha-fetoprotein levels before and after intraumbilical vein injection did not show evidence of fetomaternal transfusion." ]	Routine use of oxytocin or any other uterotonics with normal saline via umbilical vein injection is not recommended until new evidence is available. Further research should be conducted to show effectiveness of oxytocin with normal saline via umbilical vein injection.
CD003516	[ "1867580", "1789830", "12070950", "12817353", "20063224" ]	[ "Immediate postoperative oral hydration after caesarean section.", "Randomised controlled trial comparing oral and intravenous rehydration therapy in children with diarrhoea.", "Management of meningitis in children with oral fluid restriction or intravenous fluid at maintenance volumes: a randomised trial.", "Modifying dyspepsia management in primary care: a cluster randomised controlled trial of educational outreach compared with passive guideline dissemination.", "A randomized trial of increased intravenous hydration in labor when oral fluid is unrestricted." ]	[ "A study was carried out to assess the effects of immediate postoperative oral rehydration in 51 unpremedicated women undergoing caesarean section under epidural anesthesia. The patients were randomly assigned to 2 groups: group 1 (n = 22)--fasting at least until 24 hours after the end of the operation, and group 2 (n = 29)--receiving immediate oral intake of fluids (water, tea or coffee with sugar) without limitation of quantity. The 2 groups were compared for the occurrence of postoperative nausea and vomiting, onset of peristalsis, rectal gas emission, first bowel movement, and possible complications. The results demonstrate no significant differences between the parturients who drank immediately postoperatively as compared to those in whom oral fluid intake was delayed for 24 hours or more. It is concluded that immediate postoperative oral rehydration had no harmful effect upon peristalsis post-caesarean section.", "To determine the effectiveness of oral rehydration in children with moderate dehydration caused by gastroenteritis, and to compare the complications of oral and intravenous treatment.\n Randomised controlled trial.\n Emergency department and infectious diseases ward in a large urban teaching hospital.\n 111 children aged 3-36 months who had been previously healthy, had had diarrhoea for seven days or less, had clinical signs of dehydration, and were not in shock. Six children were withdrawn because the diagnosis was incorrect (four in oral group, two in intravenous group) and one (oral group) was withdrawn at her parents' request.\n Oral rehydration fluid was given by mouth or nasogastric tube, or both to 52 children. The remaining 52 received intravenous rehydration fluids but were allowed to drink.\n Success or failure of rehydration. Number of times child vomited or passed stool after starting treatment. Time taken to rehydrate.\n Oral treatment failed in two children (failure rate 3.8%, upper 95% confidence limit 11.6%) and intravenous treatment in none. Vomiting was more common in the oral group (p less than 0.01): 26 of 50 children (52%) in the oral group and 11 of 50 (22%) in the intravenous group vomited during rehydration. There was no significant difference between the two treatment groups in the number of stools passed during rehydration (p = 0.09). None of the children had serious complications of treatment.\n Rehydration by mouth or nasogastric tube is a safe and effective treatment for moderately dehydrated children with gastroenteritis.", "A multi-centre randomised open trial was done to determine whether moderate oral fluid restriction or intravenous fluid at full maintenance volumes would result in a better outcome for children with bacterial meningitis in Papua New Guinea, and what clinical signs could guide fluid management. Children with clinical signs and cerebrospinal fluid suggestive of bacterial meningitis received either breast milk by nasogastric tube at 60% of normal maintenance volumes (n = 172) or intravenous half-normal saline and 5% dextrose at 100% of normal maintenance volumes (n = 174) for the 1st 48 hrs of treatment. An adverse outcome was death or severe neurological sequelae, and a good outcome was defined as intact survival or survival with at worst mild-to-moderate neurological sequelae. The probability of an adverse outcome was 24.7% in the intravenous group and 33.1% in the oral-restricted group, but the difference was not statistically significant (RR 0.75, 0.53-1.04, p = 0.08). Sunken eyes or reduced skin turgor at presentation were risk factors for an adverse outcome (OR 5.70, 95% CI 2.87-11.29) and were most strongly associated with adverse outcome in the fluid-restricted group. Eyelid oedema during treatment was also a risk factor for an adverse outcome (OR 2.54, 95% CI 1.36-4.75) and eyelid oedema was much more common in the intravenous group (26%) than in the restricted group (5%). For many children with bacterial meningitis in less developed countries, moderate fluid restriction is unnecessary and will be harmful; a normal state of hydration should be achieved but over-hydration should be avoided. Giving 100% of normal maintenance fluids, especially with intravenous hypotonic fluid, will lead to oedema in up to one quarter of children with bacterial meningitis. If additional intravenous fluids are required for children with meningitis, an isotonic solution should be used.", "Quality improvement initiatives in health services rely upon the effective introduction of clinical practice guidelines. However, even well constructed guidelines have little effect unless supported by dissemination and implementation strategies.\n To test the effectiveness of 'educational outreach' as a strategy for facilitating the uptake of dyspepsia management guidelines in primary care.\n A pragmatic, cluster-randomised controlled trial of guideline introduction, comparing educational outreach with postal guideline dissemination alone.\n One-hundred and fourteen general practices (233 general practitioners) in the Salford and Trafford Health authority catchment area in the northwest of England.\n All practices received guidelines by post in July 1997. The intervention group practices began to receive educational outreach three months later. This consisted of practice-based seminars with hospital specialists at which guideline recommendations were appraised, and implementation plans formulated. Seminars were followed up with 'reinforcement' visits after a further 12 weeks. Outcome measures were: (a) the appropriateness of referral for; and (b) findings at, open access upper gastrointestinal endoscopy; (c) costs of GP prescriptions for acid-suppressing drugs, and (d) the use of laboratory-based serological tests for Helicobacter pylori. Data were collected for seven months before and/or after the intervention and analysed by intention-to-treat.\n (a) The proportion of appropriate referrals was higher in the intervention group in the six-month post-intervention period (practice medians: control = 50.0%, intervention = 63.9%, P < 0.05); (b) the proportion of major findings at endoscopy did not alter significantly; (c) there was a greater rise in overall expenditure on acid-suppressing drugs in the intervention as compared with the control group (+8% versus +2%, P = 0.005); and (d) the median testing rate per practice for H pylori in the post-intervention period was significantly greater in the intervention group (four versus O, P < 0.001).\n This study suggests that educational outreach may be more effective than passive guideline dissemination in changing clinical behaviour. It also demonstrates that unpredictable and unanticipated outcomes may emerge.", "Increased intravenous (IV) hydration is associated with decreased labor duration and oxytocin augmentation in nulliparous women when oral fluid is restricted. The objective of this study was to determine the effect of increased IV hydration on the duration of labor when access to oral fluid was unrestricted.\n Term, nulliparous women with uncomplicated singleton pregnancies were randomly assigned to receive lactated ringers at 250 ml per hour (IV fluid group) throughout active labor or usual care. All women were allowed unrestricted access to oral fluids.\n Eighty women completed the study, 37 in the IV fluid group and 43 in the usual care group. There was no difference in the primary outcome of total duration of labor (9.5 versus 9.4 hours) or in the secondary outcomes of duration of the first stage (7.9 versus 8.0 hours), duration of second stage (1.6 versus 1.4 hours), or rate of oxytocin augmentation (51% versus 44%).\n Increased IV hydration does not decrease labor duration in nulliparous women when access to oral fluid is unrestricted." ]	There was no evidence from the limited randomised trials reviewed, to justify a policy of withholding oral fluids after uncomplicatedcaesarean section. Further research is justified.
CD008019	[ "20677024", "9158305", "19566557" ]	[ "A randomized controlled study investigating the necessity of routine cervical dilatation during elective cesarean section.", "Preinduction cervical ripening: prostaglandin E2 gel vs hygroscopic mechanical dilator.", "Is routine cervical dilatation necessary during elective caesarean section? A randomised controlled trial." ]	[ "To investigate if it was necessary to dilate the cervix routinely during elective cesarean section and to determine the effects of this traditional maneuver on maternal morbidity.\n A total of 150 patients meeting eligibility criteria were enrolled in this prospective, randomized controlled study. Patients were allocated randomly into cervical dilatation group or non-dilated group. In the cervical dilatation group, the surgeon performed cervical dilatation by inserting a double-gloved index finger into the cervical canal of the patients after extraction of placenta and membranes. Endometrial cavity thickness of the patients at postoperative 24 h, development of postoperative febrile-infectious morbidity and postoperative hemoglobin levels were evaluated and compared between the groups.\n The two groups were comparable with regard to demographic and clinical properties. Mean postoperative endometrial cavity thickness of the dilated group was significantly less than the non-dilated group (6.87 ± 2.50, 9.51 ± 3.35 respectively, p < 0.0001). The level of hemoglobin reduction was comparable between the groups (p = 0.37). Febrile morbidity was seen in one patient in the dilated group. Endometritis or wound infection was not encountered in either group during the puerperium.\n Cervical dilatation seems to be an unnecessary intervention during the cesarean section.", "To evaluate the efficacy and safety of hygroscopic mechanical dilators (Dilapan) for ripening the pregnant cervix prior to induction of labour at or near term and to compare it with an intracervical PGE2 gel (Prepidil).\n One hundred and eighty-five women (69 nulliparae, 116 multiparae) at term with singleton pregnancies in cephalic presentation, who were scheduled for induction of labour in the labour ward at the National University Hospital, but had an unfavourable cervical score were randomized into 2 groups by random number table. In group 1 (Prepidil), 0.5 mg of PGE2 in 2.5 ml of triacetin gel was inserted into the endocervical canal. In women in group 2 (Dilapan) upto a maximum of 4 hygroscopic dilators were placed in the endocervical canal. If labour did not ensue at the end of 12 hours of ripening, the cervical score was assessed, amniotomy was performed and oxytocin commenced. Neonatal and obstetric outcome was compared, statistical analysis performed using Chi-square, and t-tests.\n Significantly more women in the group who received Dilapan for cervical ripening required amniotomy and oxytocin for induction of labour > 12 hours after priming compared with the group who received Prepidil (p < 0.001). Operative delivery for no progress and fetal distress respectively was similar in the 2 groups. The number of cases of hyperstimulation were higher in the Prepidil group but did not result in an increased incidence of operative deliveries for fetal distress. There was one neonatal death and one case of neonatal sepsis in the Dilapan group. Uterine rupture occurred in 1 woman who received Prepidil.\n Dilapan, a mechanical method of cervical ripening is as effective as the more widely accepted mode of ripening with an endocervical PGE2 gel in achieving vaginal delivery. Dilapan would be useful for cervical priming prior to induction of labour in places where prostaglandins are not available because of cost and the need for a cold chain.", "The purpose of this prospective randomised study was to determine the effect of routine cervical dilatation during elective caesarean section on maternal morbidity.\n Participants with indication for elective caesarean section were randomly allocated to two groups. Group A (n = 200) women with intraoperative cervical dilatation; group B (n = 200) women with no intraoperative cervical dilatation.\n No demographic differences were observed between groups. There was no significant difference between groups in infectious morbidity (P = 0.87) (relative risk (RR) 1.11, 95% confidence interval (CI) 0.58-2.11), endometritis (P = 0.72) (RR 1.68, 95% CI 0.39-7.14), febrile morbidity (P = 0.66) (RR 1.21, 95% CI 0.51-2.87), wound infection (P = 0.82) (RR 1.11, 95% CI 0.44-2.81), endometritis (P = 0.72) (RR 1.68, 95% CI 0.39-7.14) or urinary tract infection (P = 1.00) (RR 1.00, 95% CI 0.28-3.50), and estimated blood loss (P = 0.2). However, group A had longer operative times compared with the group B (P = 0.01).\n Intraoperative digital cervical dilatation during elective caesarean section did not reduce blood loss and postoperative infectious morbidity. The routine digital cervical dilatation during elective caesarean section is not recommended." ]	There was insufficient evidence of mechanical dilatation of the cervix at non-labour caesarean section for reducing postoperative morbidity. Further randomised controlled trials with adequate methodological quality comparing intraoperative cervical dilatation using a finger, sponge forceps or other instrument during non-labour caesarean section versus no mechanical dilatation for reducing postoperative morbidity are needed.
CD006019	[ "3133327", "11483335", "8632574", "9123738", "11111188", "15084760", "16257791", "10791373", "14767287", "13129633", "10588962", "15817329", "20619634", "17105795", "16099293", "8826739", "8776812", "19433689", "15629605", "11747326", "8791047" ]	[ "Adjuvant estrogen following radiation therapy for stage C adenocarcinoma of the prostate: long-term results of a prospective randomized study.", "Phase III radiation therapy oncology group (RTOG) trial 86-10 of androgen deprivation adjuvant to definitive radiotherapy in locally advanced carcinoma of the prostate.", "Randomized study of neoadjuvant testicular androgen ablation therapy before radical prostatectomy in men with clinically localized prostate cancer.", "Neoadjuvant hormonal therapy: the Canadian experience.", "4-Year follow-up results of a European prospective randomized study on neoadjuvant hormonal therapy prior to radical prostatectomy in T2-3N0M0 prostate cancer. European Study Group on Neoadjuvant Treatment of Prostate Cancer.", "Neoadjuvant hormone treatment with leuprolide acetate depot 3.75 mg and cyproterone acetate, before radical prostatectomy: a randomized study.", "Short-term androgen deprivation and radiotherapy for locally advanced prostate cancer: results from the Trans-Tasman Radiation Oncology Group 96.01 randomised controlled trial.", "Comparison of radiotherapy alone with radiotherapy plus hyperthermia in locally advanced pelvic tumours: a prospective, randomised, multicentre trial. Dutch Deep Hyperthermia Group.", "The efficacy and sequencing of a short course of androgen suppression on freedom from biochemical failure when administered with radiation therapy for T2-T3 prostate cancer.", "Acceptability of short term neo-adjuvant androgen deprivation in patients with locally advanced prostate cancer.", "Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer.", "Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma--long-term results of phase III RTOG 85-31.", "Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer--results from two randomised studies.", "Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial.", "Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911).", "Adjuvant VHF therapy in locally recurrent and primary unresectable rectal cancer.", "Combination treatment versus LHRH alone in advanced prostatic cancer.", "Phase III postoperative adjuvant radiotherapy after radical prostatectomy compared with radical prostatectomy alone in pT3 prostate cancer with postoperative undetectable prostate-specific antigen: ARO 96-02/AUO AP 09/95.", "Regional hyperthermia combined with radiotherapy for uterine cervical cancers: a multi-institutional prospective randomized trial of the international atomic energy agency.", "Evaluation of nurse-led follow up for patients undergoing pelvic radiotherapy.", "The risk of malignancy in the surgical margin at radical prostatectomy reduced almost three-fold in patients given neo-adjuvant hormone treatment." ]	[ "Seventy-eight patients with clinical Stage C adenocarcinoma of the prostate were prospectively randomized to receive either radiation alone or radiation and adjuvant estrogen (diethylstilbestrol). No patient had received any prior definitive treatment for cancer. Forty patients were randomized to receive radiotherapy only and 38 patients to receive radiotherapy and estrogen. The median follow-up for all surviving patients was 14.5 years. Whether analyzed according to the original randomization or according to the treatment actually received, disease-free survival in the adjuvant estrogen group was strikingly and significantly higher than in the radiation-only group. At 5, 10, and 15 years patients receiving adjuvant estrogen had respective disease-free survival rates of 71%, 63%, and 63% compared with 49%, 43%, and 35% in patients having radiation only (p = 0.008). However, because of greater intercurrent disease-related mortality in patients receiving estrogen, there was no improvement in survival. This study suggests that a prospective randomized evaluation of early androgen deprivation with orchiectomy or with one of the nonestrogenic agents should be undertaken and that patients receiving early androgen deprivation should not be included in series reporting on the curative potential of radiation as a single modality.", "To test the hypothesis that androgen ablation before and during radiotherapy for locally advanced carcinoma of the prostate may, by reducing tumor bulk and enhancing tumor cell kill, improve locoregional control and ultimately survival.\n The study was conducted from 1987 to 1991. Eligible patients were those with bulky tumors (T2--T4) with or without pelvic lymph node involvement and without evidence of distant metastases. They were randomized to receive goserelin, 3.6 mg every 4 weeks; and flutamide, 250 mg t.i.d. for 2 months before radiation therapy and during radiation therapy (Arm I), or radiation therapy alone (Arm II). Of 471 randomized patients, 456 were evaluable: 226 on Arm I and 230 on Arm II.\n As of November 1999, the median follow-up has reached 6.7 years for all patients and 8.6 years for alive patients. At 8 years, androgen ablation has been associated with an improvement in local control (42% vs. 30%, p = 0.016), reduction in the incidence of distant metastases (34% vs. 45%, p = 0.04), disease-free survival (33% vs. 21%, p = 0.004), biochemical disease-free survival = PSA <1.5 (24% vs. 10%, p < 0.0001), and cause-specific mortality (23% vs. 31%, p = 0.05). However, subset analysis indicates that the beneficial effect of short-term androgen ablation appears preferentially in patients with Gleason score 2--6. In that population, there is a highly significant improvement in all endpoints, including survival (70% vs. 52%, p = 0.015). In patients with Gleason 7--10 tumors, the regimen has not resulted in a significant enhancement in either locoregional control or survival.\n In patients with Gleason score 2--6 carcinoma of the prostate, a short course of androgen ablation administered before and during radiotherapy has been associated with a highly significant improvement in local control, reduction in disease progression, and overall survival.", "We determined whether 12 weeks of neoadjuvant testicular androgen ablation therapy using a luteinizing hormone-releasing hormone agonist could improve pathological outcomes in men undergoing radical retropubic prostatectomy for clinically localized (stages T1C, T2A and T2B) prostatic carcinoma.\n A total of 56 participants was randomized to receive either monthly injections of a luteinizing hormone-releasing hormone agonist at 4-week intervals followed by radical retropubic prostatectomy (28) or to undergo immediate radical retropubic prostatectomy alone (28). Operations were performed via similar technique and all prostatic specimens were processed histologically in their entirety.\n There was no improvement in pathological outcome using luteinizing hormone-releasing hormone agonist preoperatively compared to surgery alone. Of 28 men undergoing immediate radical retropubic prostatectomy 23 had organ-confined (17) or specimen-confined (6) disease versus 22 of 28 who received luteinizing hormone-releasing hormone neoadjuvant therapy for 12 weeks preoperatively (16 with organ-confined and 6 with specimen-confined disease, p = 1.00). In addition, when the study population was analyzed by pretreatment prostate specific antigen (PSA) levels (10 ng./ml. or less, or greater than 10 ng./ml/) there was also no difference in pathological outcome (p = 0.65 for PSA greater than 10 and p = 0.32 for PSA less than 10).\n Neoadjuvant androgen ablation therapy for 12 weeks before radical prostatectomy in patients with clinically localized adenocarcinoma of the prostate does not result in improved pathological outcomes.", "To assess the effect of neoadjuvant combination therapy with the antiandrogen flutamide and a luteinizing-hormone-releasing hormone (LHRH) agonist administered for 3 months before radical prostatectomy, compared with surgery alone in early stage prostate cancer on histopathologic findings at surgery and serum prostate-specific antigen (PSA).\n A sample of 161 randomly screened patients diagnosed as having stage B (134 patients) or C (27 patients) prostate cancer were randomly assigned to radical prostatectomy alone or to 3 months of neoadjuvant combination therapy with the antiandrogen flutamide and an LHRH agonist before radical prostatectomy.\n Neoadjuvant combination therapy before radical prostatectomy decreased cancer-positive surgical margins from 33.8% in the control group to only 7.8%, thus leaving 92.2% of patients with negative margins at surgery. A net 54% improvement of staging was observed in favor of combination therapy. Organ-confined disease, on the other hand, increased from 49.3% to 77.8% of patients after 3 months of combination therapy, for a 57.8% increase in the incidence of organ-confined disease. No cancer was found in 6 (6.7%) prostatectomy specimens from the treated group. A close correlation was found between serum PSA at diagnosis and the stage of the disease at surgery. Upstaging increased from 30% at serum PSA values of 0 to 3.0 ng/mL up to 100% at serum PSA values above 15 ng/mL.\n Although long-term follow-up of these patients is required to determine the impact on survival, the marked influence of neoadjuvant combination therapy on the stage of the disease suggests the possibility of a major improvement in the morbidity and mortality from prostate cancer.", "To evaluate the long-term effects of 3-month neoadjuvant hormonal treatment in patients treated by radical prostatectomy for locally confined prostate cancer.\n We report the results of 402 patients (220 with a clinical T2 tumor and 182 with a clinical T3 tumor) of whom 192 randomly received neoadjuvant total androgen deprivation using a LHRH analogue (goserelin) plus flutamide for a period of 3 months and 210 underwent radical prostatectomy only.\n 'Clinical downstaging' was seen in 30% of cases in the neoadjuvantly treated group (NEO). 'Pathological downstaging' occurred in 7 and 15% of cases in the direct radical prostatectomy (DP) group and the NEO group, respectively (p<0.01). In patients with clinical T2 as well as in patients with clinical T3 tumors, a significant difference in the number of positive margins was shown in favor of the NEO group (cT2, p<0.01; cT3, p = 0.01). This advantage, although there was a trend in favor of the NEO group, specifically in cT2 tumors, did not translate in a significantly better PSA progression rate (p = 0.18). However, when evaluating the local control rate in cT2 tumors, we observed local recurrence in 3 of 102 (3%) patients in the NEO group versus 12 of 114 (11%) patients in the DP group. The difference is statistically significant (p = 0.03). In the cT3 group, this difference was not statistically significant (NEO group: 15 of 87 (17%), and DP group: 21 of 95 (22%) patients; p = 0.41).\n In this study, the clinical revelance of pathological downstaging and the lower percentage of patients with positive margins in the neoadjuvantly treated group with a clinical T2 tumor is not confirmed by a lower PSA progression rate. However, this study indicates that there may be a trend that this advantage in favor of the NEO group directly translates into a better local control rate in clinical T2 tumors. Better local control in cT2 tumors is only going to be of relevance if subsequently you can show that there is a better survival for these patients. Unfortunately, this article reports a study which is not yet mature enough to show relevant information. Presently, neoadjuvant therapy should not be given outside clinical research settings.", "To assess the effect of neoadjuvant hormone treatment before radical prostatectomy on: tumor/prostate volume, prostate-specific antigen (PSA) and testosterone levels, surgical margin status and tumor stage, and the ease of surgery following treatment.\n Patients with clinically localized prostatic carcinoma were randomized to receive leuprolide acetate depot 3.75 mg once a month for 3 months and cyproterone acetate 300 mg once a week for 3 weeks prior to surgery (group A). A control group of patients had surgery without any pretreatment (group B).\n 167 patients were evaluated for the efficacy parameters. In group A, 31% of patients had a reduction in tumor/prostate volume following hormone therapy. PSA and testosterone levels were significantly reduced (p = 0.0001) in patients in group A compared to basal values. Centralized histopathological data evaluated in 145 patients (group A and 75 group B) showed that more patients in group B had tumors at stages T3A and T3B than in group A; this difference was close to significance (p = 0.057). Positive surgical margins were more common in group B (60% of patients) compared to group A (39% of patients). Similarly lymph node involvement was more common in group B compared to group A (11 versus 3%). There was little difference between the 2 study groups for the other surgical parameters assessed (ease of dissection, duration of surgery, blood loss).\n Neoadjuvant hormone therapy before radical prostatectomy has some effects in the treatment of prostate cancer. However, long-term follow-up of patients is needed to assess the impact of this therapy on morbidity and mortality.\n Copyright 2004 S. Karger AG, Basel", "Androgen deprivation is an established treatment regimen for disseminated prostate cancer; however, its role in patients with localised cancer is less clear. We did a large randomised controlled trial to determine whether 3 months or 6 months of androgen deprivation given before and during radiotherapy improves outcomes for patients with locally advanced prostate cancer.\n 818 men with locally advanced prostate cancer were randomly assigned to: no androgen deprivation (ie, radiotherapy alone: 66 Gy in 33 fractions of 2 Gy per day over 6.5-7.0 weeks to the prostate and seminal vesicles); 3 months' androgen deprivation with 3.6 mg goserelin given subcutaneously every month and 250 mg flutamide given orally three times a day starting 2 months before radiotherapy (same regimen as control group); or 6 months' androgen deprivation, with the same regimen, starting 5 months before radiotherapy (same regimen as control group). Primary endpoints were time to local failure and prostate-cancer-specific survival; secondary endpoints were distant failure, disease-free survival, and freedom from salvage treatment. Analyses were done by intention to treat.\n 802 (98%) patients were eligible for analysis. Median follow-up was 5.9 years (range 0.1-8.5). Compared with patients assigned no androgen deprivation, those assigned 3 months' treatment had significantly improved local failure (hazard ratio [HR] 0.56 [95% CI 0.39-0.79], p=0.001), biochemical failure-free survival (0.70 [0.56-0.88], p=0.002), disease-free survival (0.65 [0.52-0.80], p=0.0001), and freedom from salvage treatment (0.73 [0.56-0.96], p=0.025). 6 months' androgen deprivation significantly improved local failure (0.42 [0.28-0.62], p<0.0001), biochemical failure-free survival (0.58 [0.46-0.74], p<0.0001), disease-free survival (0.56 [0.45-0.69], p<0.0001), freedom from salvage treatment (0.53 [0.40-0.71], p<0.0001), distant failure (0.67 [0.45-0.99], p=0.046) and prostate-cancer-specific survival (0.56 [0.32-0.98], p=0.04) compared with no androgen deprivation.\n 6 months' androgen deprivation given before and during radiotherapy improves the outlook of patients with locally advanced prostate cancer. Further follow-up is needed to estimate precisely the size of survival benefits. Increased radiation doses and additional periods of androgen deprivation might lead to further benefit.", "Local-control rates after radiotherapy for locally advanced tumours of the bladder, cervix, and rectum are disappointing. We investigated the effect of adding hyperthermia to standard radiotherapy.\n The study was a prospective, randomised, multicentre trial. 358 patients were enrolled from 1990 to 1996, in cancer centres in the Netherlands, who had bladder cancer stages T2, T3, or T4, NO, MO, cervical cancer stages IIB, IIIB, or IV, or rectal cancer stage M0-1 were assessed. Patients were randomly assigned radiotherapy (median total dose 65 Gy) alone (n=176) or radiotherapy plus hyperthermia (n=182). Our primary endpoints were complete response and duration of local control. We did the analysis by intention to treat.\n Complete-response rates were 39% after radiotherapy and 55% after radiotherapy plus hyperthermia (p<0.001). The duration of local control was significantly longer with radiotherapy plus hyperthermia than with radiotherapy alone (p=0.04). Treatment effect did not differ significantly by tumour site, but the addition of hyperthermia seemed to be most important for cervical cancer, for which the complete-response rate with radiotherapy plus hyperthermia was 83% compared with 57% after radiotherapy alone (p=0.003). 3-year overall survival was 27% in the radiotherapy group and 51% in the radiotherapy plus hyperthermia group. For bladder cancer, an initial difference in local control disappeared during follow-up.\n Hyperthermia in addition to standard radiotherapy may be especially useful in locally advanced cervical tumours. Studies of larger numbers of patients are needed for other pelvic tumour sites before practical recommendations can be made.", "We evaluated the benefits and sequencing of androgen suppression (AS) administered with external beam radiation therapy (EBRT) in T2-T3 prostate cancers.\n Between 1990 and 1999, 481 patients were entered in 2 successive, prospective, randomized studies, including 161 in the study 1 and 325 in study 2. Eligible patients had clinical stages T2-T3 prostate cancer. In the first study (L-101) subjects were randomly allocated among EBRT alone (group 1), EBRT preceded by 3 months of AS (group 2), and neoadjuvant, concomitant and adjuvant AS for a total of 10 months (group 3). In the second study (L-200) we analyzed neoadjuvant and concomitant AS (total 5 months) vs neoadjuvant, concomitant and short course adjuvant (total 10 months) AS with EBRT. In each study we used a total AS (a luteinizing hormone-releasing hormone agonist plus an antiandrogen) and a standard dose of radiation therapy at that time. Patient characteristics were well balanced in regard to age, stage, prostate specific antigen and Gleason score. No biochemical evidence of disease (BNED) was defined as an end point according to the Vancouver rule.\n In the study 1 at a median followup of 5 years 7-year biochemical-free survival rates were 42%, 66% and 69% in groups 1 to 3, respectively. BNED was significantly different between groups 1 and 2 (p = 0.009) and between groups 1 and 3 (p = 0.003) but not between groups 2 and 3 (p = 0.6). Multivariate analysis using a Cox proportional hazards model showed an HR of 6.1 for Gleason score (p = 0.001), 1.4 for PSA (p = 0.002), 0.5 for group 1 vs group 2 (p = 0.01) and 0.35 for group 1 vs group 3 (p = 0.008). In study 2 BNED at 4 years was 65%. There was no significant difference between arms 1 and 2 (p = 0.55).\n The analysis of study 1 shows a benefit of using a short course of neoadjuvant AS with EBRT vs EBRT alone for localized T2-T3 prostate cancers. Moreover, in each study adding a short course of adjuvant AS after neoadjuvant 1 provided no more advantage in these patients.", "To determine the acceptability of short term neo-adjuvant maximal androgen deprivation (MAD) to patients treated with external beam radiation for locally advanced prostate cancer.\n Between 1996 and 2000, 818 patients with locally advanced, but non-metastatic, prostate cancer were entered into a randomised clinical trial (TROG 96.01), which compared radiation treatment alone with the same radiation treatment and 3 or 6 months neo-adjuvant MAD with goserelin and flutamide. Relevant symptoms, and how troublesome they were to the patient, were scored using a self-assessment questionnaire. This was completed by the patient at registration, and at specified times during and after treatment. Patients taking flutamide had liver function tests checked at regular intervals.\n All patients have completed at least 12 months follow-up after treatment. Nearly all patients completed planned treatment with goserelin, but 27% of patients in the 6-month MAD treatment arm, and 20% in the 3-month arm, had to stop flutamide early. This was mainly due to altered liver function (up to 17% patients) and bowel side effects (up to 8% patients). However, although flutamide resulted in more bowel symptoms for patients on MAD, there was significant reduction in some urinary symptoms on this treatment. Acute bowel and urinary side effects at the end of radiation treatment were similar in all treatment arms. Side effect severity was unrelated to radiation target volume size, which was reduced by MAD, but symptomatology prior to any treatment was a powerful predictor. Of the 36% of patients who were sexually active before any treatment, the majority became inactive whilst on MAD. However, sexual activity at 12 months after radiation treatment was similar in all treatment arms, indicating that the effects of short term MAD on sexual function are reversible.\n Despite temporary effects on sexual activity, and compliance difficulties with flutamide, short-term neo-adjuvant MAD was not perceived by patients to be a major inconvenience. If neo-adjuvant MAD in the way tested can be demonstrated to lead to improved biochemical control and/or survival, then patients would view these therapeutic gains as worthwhile. Compliance with short-term goserelin was excellent, confirming that LH-RH analogues have a potential role in more long-term adjuvant treatment. However, for more protracted androgen deprivation, survival advantages and deleterious effects need to be assessed in parallel, in order to determine the optimal duration of treatment.", "Because the optimal timing of the institution of antiandrogen therapy for prostate cancer is controversial, we compared immediate and delayed treatment in patients who had minimal residual disease after radical prostatectomy.\n Ninety-eight men who underwent radical prostatectomy and pelvic lymphadenectomy and who were found to have nodal metastases were randomly assigned to receive immediate antiandrogen therapy, with either goserelin, a synthetic agonist of gonadotropin-releasing hormone, or bilateral orchiectomy, or to be followed until disease progression. The patients were assessed quarterly during the first year and then semiannually.\n After a median of 7.1 years of follow-up, 7 of 47 men who received immediate antiandrogen treatment had died, as compared with 18 of 51 men in the observation group (P=0.02). The cause of death was prostate cancer in 3 men in the immediate-treatment group and in 16 men in the observation group (P<0.01). At the time of the last follow-up, 36 men in the immediate-treatment group (77 percent) and 9 men in the observation group (18 percent) were alive and had no evidence of recurrent disease, including undetectable serum prostate-specific antigen levels (P<0.001). In the observation group, the disease recurred in 42 men; 13 of the 36 who were treated had a complete response to local treatment or hormonal therapy (or both), 16 died of prostate cancer, and 1 died of another disease. The remaining men in this group were alive with progressive disease at the time of the last follow-up or had had a recent relapse. Except for the treatment group (immediate therapy or observation), no clinical or histologic characteristic significantly influenced the outcome.\n Immediate antiandrogen therapy after radical prostatectomy and pelvic lymphadenectomy improves survival and reduces the risk of recurrence in patients with node-positive prostate cancer.", "Radiation Therapy Oncology Group protocol 85-31 was designed to evaluate the effectiveness of adjuvant androgen suppression, using goserelin, in unfavorable prognosis carcinoma of the prostate treated with definitive radiotherapy (RT).\n Eligible patients were those with palpable primary tumor extending beyond the prostate (clinical Stage T3) or those with regional lymphatic involvement. Patients who had undergone prostatectomy were eligible if penetration through the prostatic capsule to the margin of resection and/or seminal vesicle involvement was documented histologically. Stratification was based on histologic differentiation, nodal status, acid phosphatase status, and prior prostatectomy. The patients were randomized to either RT and adjuvant goserelin (Arm I) or RT alone followed by observation and application of goserelin at relapse (Arm II). In Arm I, the drug was to be started during the last week of RT and was to be continued indefinitely or until signs of progression.\n Between 1987 and 1992, when the study was closed, 977 patients were entered: 488 to Arm I and 489 to Arm II. As of July 2003, the median follow-up for all patients was 7.6 years and for living patients was 11 years. At 10 years, the absolute survival rate was significantly greater for the adjuvant arm than for the control arm: 49% vs. 39%, respectively (p = 0.002). The 10-year local failure rate for the adjuvant arm was 23% vs. 38% for the control arm (p <0.0001). The corresponding 10-year rates for the incidence of distant metastases and disease-specific mortality was 24% vs. 39% (p <0.001) and 16% vs. 22% (p = 0.0052), respectively, both in favor of the adjuvant arm.\n In a population of patients with unfavorable prognosis carcinoma of the prostate, androgen suppression applied as an adjuvant after definitive RT was associated not only with a reduction in disease progression but in a statistically significant improvement in absolute survival. The improvement in survival appeared preferentially in patients with a Gleason score of 7-10.", "Endometrial cancer patients with high grade tumours, deep myometrial invasion or advanced stage disease have a poor prognosis. Randomised studies have demonstrated the prevention of loco-regional relapses with radiotherapy (RT) with no effect on overall survival (OS). The possible additive effect of chemotherapy (CT) remains unclear. Two randomised clinical trials (NSGO-EC-9501/EORTC-55991 and MaNGO ILIADE-III) were undertaken to clarify if sequential combination of chemotherapy and radiotherapy improves progression-free survival (PFS) in high-risk endometrial cancer. The two studies were pooled.\n Patients (n=540; 534 evaluable) with operated endometrial cancer International Federation of Obstetrics and Gynaecology (FIGO) stage I-III with no residual tumour and prognostic factors implying high-risk were randomly allocated to adjuvant radiotherapy with or without sequential chemotherapy.\n In the NSGO/EORTC study, the combined modality treatment was associated with 36% reduction in the risk for relapse or death (hazard ratio (HR) 0.64, 95%confidence interval (CI) 0.41-0.99; P=0.04); two-sided tests were used. The result from the Gynaecologic Oncology group at the Mario Negri Institute (MaNGO)-study pointed in the same direction (HR 0.61), but was not significant. In the combined analysis, the estimate of risk for relapse or death was similar but with narrower confidence limits (HR 0.63, CI 0.44-0.89; P=0.009). Neither study showed significant differences in the overall survival. In the combined analysis, overall survival approached statistical significance (HR 0.69, CI 0.46-1.03; P=0.07) and cancer-specific survival (CSS) was significant (HR 0.55, CI 0.35-0.88; P=0.01).\n Addition of adjuvant chemotherapy to radiation improves progression-free survival in operated endometrial cancer patients with no residual tumour and a high-risk profile. A remaining question for future studies is if addition of radiotherapy to chemotherapy improves the results.\n Copyright 2010 Elsevier Ltd. All rights reserved.", "Despite a stage-shift to earlier cancer stages and lower tumor volumes for prostate cancer, pathologically advanced disease is detected at radical prostatectomy in 38% to 52% of patients. However, the optimal management of these patients after radical prostatectomy is unknown.\n To determine whether adjuvant radiotherapy improves metastasis-free survival in patients with stage pT3 N0 M0 prostate cancer.\n Randomized, prospective, multi-institutional, US clinical trial with enrollment between August 15, 1988, and January 1, 1997 (with database frozen for statistical analysis on September 21, 2005). Patients were 425 men with pathologically advanced prostate cancer who had undergone radical prostatectomy.\n Men were randomly assigned to receive 60 to 64 Gy of external beam radiotherapy delivered to the prostatic fossa (n = 214) or usual care plus observation (n = 211).\n Primary outcome was metastasis-free survival, defined as time to first occurrence of metastatic disease or death due to any cause. Secondary outcomes included prostate-specific antigen (PSA) relapse, recurrence-free survival, overall survival, freedom from hormonal therapy, and postoperative complications.\n Among the 425 men, median follow-up was 10.6 years (interquartile range, 9.2-12.7 years). For metastasis-free survival, 76 (35.5%) of 214 men in the adjuvant radiotherapy group were diagnosed with metastatic disease or died (median metastasis-free estimate, 14.7 years), compared with 91 (43.1%) of 211 (median metastasis-free estimate, 13.2 years) of those in the observation group (hazard ratio [HR], 0.75; 95% CI, 0.55-1.02; P = .06). There were no significant between-group differences for overall survival (71 deaths, median survival of 14.7 years for radiotherapy vs 83 deaths, median survival of 13.8 years for observation; HR, 0.80; 95% CI, 0.58-1.09; P = .16). PSA relapse (median PSA relapse-free survival, 10.3 years for radiotherapy vs 3.1 years for observation; HR, 0.43; 95% CI, 0.31-0.58; P<.001) and disease recurrence (median recurrence-free survival, 13.8 years for radiotherapy vs 9.9 years for observation; HR, 0.62; 95% CI, 0.46-0.82; P = .001) were both significantly reduced with radiotherapy. Adverse effects were more common with radiotherapy vs observation (23.8% vs 11.9%), including rectal complications (3.3% vs 0%), urethral strictures (17.8% vs 9.5%), and total urinary incontinence (6.5% vs 2.8%).\n In men who had undergone radical prostatectomy for pathologically advanced prostate cancer, adjuvant radiotherapy resulted in significantly reduced risk of PSA relapse and disease recurrence, although the improvements in metastasis-free survival and overall survival were not statistically significant. Trial Registration clinicaltrials.gov Identifier: NCT00394511.", "Local failure after prostatectomy can arise in patients with cancer extending beyond the capsule. We did a randomised controlled trial to compare radical prostatectomy followed by immediate external irradiation with prostatectomy alone for patients with positive surgical margin or pT3 prostate cancer.\n After undergoing radical retropubic prostatectomy, 503 patients were randomly assigned to a wait-and-see policy, and 502 to immediate postoperative radiotherapy (60 Gy conventional irradiation delivered over 6 weeks). Eligible patients had pN0M0 tumours and one or more pathological risk factors: capsule perforation, positive surgical margins, invasion of seminal vesicles. Our revised primary endpoint was biochemical progression-free survival. Analysis was by intention to treat.\n The median age was 65 years (IQR 61-69). After a median follow-up of 5 years, biochemical progression-free survival was significantly improved in the irradiated group (74.0%, 98% CI 68.7-79.3 vs 52.6%, 46.6-58.5; p<0.0001). Clinical progression-free survival was also significantly improved (p=0.0009). The cumulative rate of locoregional failure was significantly lower in the irradiated group (p<0.0001). Grade 2 or 3 late effects were significantly more frequent in the postoperative irradiation group (p=0.0005), but severe toxic toxicity (grade 3 or higher) were rare, with a 5-year rate of 2.6% in the wait-and-see group and 4.2% in the postoperative irradiation group (p=0.0726).\n Immediate external irradiation after radical prostatectomy improves biochemical progression-free survival and local control in patients with positive surgical margins or pT3 prostate cancer who are at high risk of progression. Further follow-up is needed to assess the effect on overall survival.", "In a prospective randomized study, 434 mHz microwave therapy combined with external beam radiotherapy (VHF + RT) was compared with standard external beam radiotherapy (RT) in controlling locally recurrent or unresectable primary adenocarcinoma of the rectum. Independent assessors documented quality of life scores, performance status, toxicities, local response to treatment, and systemic disease progression before treatment and after treatment and every 8 weeks thereafter. Of 75 patients randomized, 73 were eligible for inclusion in the study. Forty-three of these patients had local pelvic tumour recurrence only and 21 also had distant metastases. In addition, nine patients had primary inoperable carcinomas, two of whom also had metastases. Thirty-seven patients were randomized to RT and 36 to VHF + RT. The median dose of radiation in the VHF+RT arm was 4275 cGy with a median fraction size of 150 cGy and median duration of therapy of 48.5 days versus 4500 cGy in the RT-only arm with a median fraction size of 180 cGy and median duration of therapy of 38 days. These doses are unlikely to be significantly different in biological effect. No significant difference between the two groups was observed in extent and duration of local control, measures of toxicity or quality of life scores. Additionally, survival and cumulative incidence of pelvic site of first progression did not differ significantly between the groups. We conclude that VHF microwave therapy in conjunction with radiotherapy produces no therapeutic advantage over conventional radiation therapy alone in the treatment of locally recurrent rectal carcinoma.", "Androgen deprivation based on hormone manipulation is the treatment of choice in advanced prostatic cancer. The unequivocal role of adrenal androgens in the growth of prostatic cancer after medical or surgical castration requires a new logical approach (complete androgen blockade) in the treatment of advanced prostate cancer. One hundred and fifty patients with biopsy-proven advanced prostatic cancer were randomized into two groups. One group (74 patients) received leuprolide + flutamide (complete androgen blockade); the second group (76 patients) received only leuprolide and, during the first 3 weeks of treatment, cyproterone acetate (150 mg/day) to prevent flare-up phenomena. The aim of the study was to evaluate the differences between the two groups on overall survival and time to progression (log-rank test). One hundred and twenty-five patients were evaluable, 62 in the leuprolide-only group and 63 in the leuprolide + flutamide group. Median duration of follow-up was 102 weeks. No statistical difference between the two groups was observed in overall survival, in time to disease progression, and in time to treatment failure. In the combination (leuprolide + flutamide) treatment group, a positive trend for overall survival and in time to progression was observed in a subgroup of patients with good performance status and no bone metastases. We observed mild gastrointestinal toxicity (diarrhea, nausea) in the group treated with leuprolide + flutamide. The aim of this study was to compare the effectiveness of total androgen withdrawal with medical testicular suppression in advanced prostatic cancer. No significant statistical difference was observed between the two groups in overall survival and in time to progression, but probably too few patients were enrolled in each treatment arm to give a statistical interpretation of our results. We conclude that there is a positive trend in the combination treatment arm in patients with good prognostic factors.", "Local failure after radical prostatectomy (RP) is common in patients with cancer extending beyond the capsule. Two randomized trials demonstrated an advantage for adjuvant radiotherapy (RT) compared with a wait-and-see policy. We conducted a randomized, controlled clinical trial to compare RP followed by immediate RT with RP alone for patients with pT3 prostate cancer and an undetectable prostate-specific antigen (PSA) level after RP.\n After RP, 192 men were randomly assigned to a wait-and-see policy, and 193 men were assigned to immediate postoperative RT. Eligible patients had pT3 pN0 tumors. Patients who did not achieve an undetectable PSA after RP were excluded from treatment according to random assignment (n = 78; 20%). Of the remaining 307 patients, 34 patients on the RT arm did not receive RT and five patients on the wait-and-see arm received RT. Therefore, 114 patients underwent RT and 154 patients were treated with a wait-and-see policy. The primary end point was biochemical progression-free survival.\n Biochemical progression-free survival after 5 years in patients with undetectable PSA after RP was significantly improved in the RT group (72%; 95% CI, 65% to 81%; v 54%, 95% CI, 45% to 63%; hazard ratio = 0.53; 95% CI, 0.37 to 0.79; P = .0015). On univariate analysis, Gleason score more than 6 and less than 7, PSA before RP, tumor stage, and positive surgical margins were predictors of outcome. The rate of grade 3 to 4 late adverse effects was 0.3%.\n Adjuvant RT for pT3 prostate cancer with postoperatively undetectable PSA significantly reduces the risk of biochemical progression. Further follow-up is needed to assess the effect on metastases-free and overall survival.", "Hyperthermia can be used to enhance the effects of radiation, and a combined treatment may, in some circumstances, be an advantage. Uterine cervical cancer is very common in developing countries. The control of locally advanced pelvic tumors is difficult with conventional treatment modalities. Based upon the biologic rationale and in view of the recent advances in heating and thermometry techniques, radiotherapy in combination with hyperthermia was investigated in a multi-institutional prospective randomized trial sponsored by the International Atomic Energy Agency. The primary purpose was to clarify whether the combination of hyperthermia and radiotherapy improves the rate of local control, compared with radiotherapy alone.\n A total of 110 patients with biopsy-proven, locally advanced carcinoma of the uterine cervix were randomized to treatment by radiotherapy with or without hyperthermia. The patients were stratified by institution, stage, and histologic type. Each patient received external beam radiation therapy and brachytherapy. For the patients randomized to receive hyperthermia, a minimum of five sessions (60 min each, once per week) were administered, employing a radiofrequency (RF) capacitive heating device. Intratumoral temperature was measured at the first hyperthermic treatment, and at least once more during the course of treatment. The equipment and the policies and procedures at each participating institution except one (Pusan) were personally inspected at least once by the corresponding author, to ensure that quality assurance procedures were in place and were followed for treatment according to the protocol guidelines. The median follow-up period was 466 days for all the patients and 512 days for the surviving patients.\n The two arms were well balanced with regard to the patient factors, tumor factors, and treatment factors. The overall survival rate at 3 years was 73.2%, and the local control rate was 68.5%. There were no significant differences between the patients treated with or without hyperthermia, either with regard to the survival (p = 0.1893) or the rate of local control (p = 0.58). The survival was significantly worse among the patients with Stage IIb disease who received hyperthermia (p = 0.0162) although there was no difference in their rate of local control (p = 0.7988). Further analysis is necessary to determine if the difference in survival is due to a greater incidence of distant metastases or some other cause. Acute Grade 2-3 toxicity was seen in 10/55 patients (18%) treated by hyperthermia and in 2/55 of the patients (4%) treated without hyperthermia (p = 0.01). There was no significant difference in the late toxicity observed in the two arms.\n This prospective randomized study failed to show any benefit from the addition of hyperthermia to radiotherapy in the treatment of locally advanced carcinoma of the uterine cervix. The acute toxicity was significantly greater among the patients receiving hyperthermia, and the survival was significantly worse among the Stage IIb patients receiving hyperthermia even though there was no difference in the local control rate.", "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 investigate the outcome of neo-adjuvant hormone treatment before radical prostatectomy regarding local tumour extension, peri-operative blood loss and operation time.\n Of 111 surgically treated patients with prostate cancer (T1b-T3a, N0, M0, G1-3), 55 were randomised to immediate radical prostatectomy and 56 to 3 months of neo-adjuvant treatment with triptorelin (3.75 mg i.m. every 28 days) and cyproterone acetate (50 mg b.i.d. for 3 weeks to prevent flare).\n No differences were found in blood loss or operation time but patients who had neo-adjuvant treatment had a significantly lower frequency of positive margins (41 vs. 23%, p = 0.013). Conclusion: Neo-adjuvant treatment does not facilitate radical prostatectomy but may improve the chance of local cure. This must, however, be documented with long-term follow-up in randomised patients." ]	Hormone therapy combined with either prostatectomy or radiotherapy is associated with significant clinical benefits in patients with local or locally advanced prostate cancer. Significant local control may be achieved when given prior to prostatectomy or radiotherapy, which may improve patient's quality of life. When given adjuvant to these primary therapies, hormone therapy, not only provides a method for local control, but there is also evidence for a significant survival advantage. However, hormone therapy is associated with significant side effects, such as hot flushes and gynaecomastia, as well as cost implications. The decision to use hormone therapy should, therefore, be taken at a local level, between the patient, clinician and policy maker, taking into account the clinical benefits, toxicity and cost. More research is needed to guide the choice, the duration, and the schedule of hormonal deprivation therapy, and the impact of long-term hormone therapy with regard to toxicity and the patient's quality of life.
CD005275	[ "15668775", "2965809", "3628103", "2521930", "2961394", "12045509" ]	[ "The effect of insoles on the incidence and severity of low back pain among workers whose job involves long-distance walking.", "Shoe insoles in the workplace.", "Effect of viscoelastic insoles on pain.", "The secondary prevention of low back pain: a controlled study with follow-up.", "Back pain and sciatica: controlled trials of manipulation, traction, sclerosant and epidural injections.", "Effectiveness of four conservative treatments for subacute low back pain: a randomized clinical trial." ]	[ "The prevalence and incidence of low back pain in general society is high. Workers whose job involves walking long distances have an even higher tendency to suffer from low back pain. A positive effect of insoles in reducing low back pain was found in professional sports players. This was not examined on people whose job involves walking long distances. In this double blind prospective study we examined the effectiveness of insoles constructed in a computerized method to placebo insoles in 58 employees whose work entailed extensive walking and who suffered from low back pain. The evaluation was performed by the MILLION questionnaire, which is considered as a valid questionnaire for evaluation of low back pain. We calculated the differences of the pain intensity before and after the intervention, in the employees using the insoles manufactured by computer in comparison to the users of the placebo insoles. In each group, the analysis was performed in comparison to the baseline. A total of 81% of the employees preferred the real insoles as effective and comfortable in comparison to 19% of the users of the placebo insoles (P<0.05). The results of this study indicate a substantial improvement in the low back pain after the use of the true insoles. The average pain intensity according to the MILLION questionnaire before the use of the insoles was 5.46. However, after the use of the real insoles and the placebo insoles, the average pain intensity decreased to 3.96 and 5.11, respectively. The difference of the average pain intensity at the start of the study and after the use of the real insoles was significant: -1.49 (P=0.0001), whereas this difference after the use of the placebo insoles was not significant: -0.31 (P=0.1189). The reported severity of pain also decreased significantly: a level 5 pain and above was reported by 77% of the subjects at the start of the study. After the use of the real insoles only 37.9% of the subjects reported a similar degree of pain severity, and 50% of the subjects did so after the use of the placebo insoles (P< 0.05). We did not find a link between low back pain and other variables such as gender, age, number of offspring, work seniority, smoking, previous use of insoles and previous medication. This study demonstrates that the low back pain decreased significantly after the use of real insoles compared to placebo ones.", "Ninety-six women participated in a crossover study to evaluate the effectiveness of viscoelastic polyurethane insoles in reducing back, leg, and foot pain among adults who spend the majority of each work day standing. Twenty-five of the subjects reported that the insoles made their shoes too tight to be comfortable. The remainder, however, found the insoles very comfortable (P less than .002, Wilcoxon, signed-rank test) and reported significant reductions in back pain (P less than .02), foot pain (P less than .03), and leg pain (P less than .007). When these subjects were asked whether they would prefer to wear their shoes alone or with insoles, the preference for insoles was overwhelming (P less than .007, back; P less than .03, leg; and P less than .009, foot pain). It is concluded that viscoelastic insoles can effectively improve comfort and reduce back, leg, and foot pain in individuals who must stand throughout the day.", "The purpose of this study was to assess the effect of viscoelastic shoe inserts on pain in nursing students. Students (N = 100) were randomly assigned to control and viscoelastic groups. The viscoelastic group used viscoelastic insoles in their work shoes for five weeks. A pain questionnaire was used to measure location and intensity of post-work pain. The questionnaire was administered as a pre-test and after five weeks. Post-test comparisons between groups indicated significant differences which were not present at pre-test. The viscoelastic group reported a significant peripheral shift in pain location from back to lower extremity; the viscoelastic group also showed significant changes in duration of post-work pain and frequency of pain during the workday. The clinical efficacy of viscoelastic shoe inserts for modifying weight bearing-induced back pain is supported. Further clinical research into the therapeutic and prophylactic value of shock-attenuating shoe inserts for healthy as well as patient populations is advocated.", "The current investigation studied the effectiveness of a secondary prevention program for nurses with back pain who were deemed at risk for developing a chronic problem. A 2 X 3 repeated measures design was employed with 2 groups and 3 assessment periods. The treatment group received an intervention designed to reduce current problems, but above all to prevent reinjury and minor pains from becoming chronic medical problems, and it included a physical and behavioral therapy package. The control group was placed on a waiting-list. Results indicated that the treatment group had significantly greater improvements than the control group for pain intensity, anxiety, sleep quality and fatigue ratings, observed pain behavior, activities, mood, and helplessness. These differences were generally maintained at the 6 month follow-up. In addition, the treatment group broke a trend for increasing amounts of pain-related absenteeism, while the control group did not. Taken as a whole, the results suggest that a secondary prevention program aimed at altering life style factors may represent an effective method for dealing with musculoskeletal pain problems.", "Four treatment regimens for patients with specified combinations of low back pain and sciatica were evaluated. The largest group studied had low back pain with limited straight-leg raising (SLR) and in them the beneficial effect of manipulation in hastening pain relief was highly significant. In similar patients without limitation of SLR, the effect was of borderline significance. In all the other groups, treated patients also recovered more quickly than their controls. Traction, for patients with low back pain and sciatica, and epidural injections when a root palsy was present also produced some significant pain relief. The effect of sclerosants for back pain was less clear.", "A randomized, assessor-blinded clinical trial was conducted.\n To investigate the relative effectiveness of three manual treatments and back school for patients with subacute low back pain.\n Literature comparing the relative effectiveness of specific therapies for low back pain is limited.\n Among the 5925 inquiries, 206 patients met the specific admission criteria, and 200 patients randomly received one of four treatments for 3 weeks: back school, joint manipulation, myofascial therapy, and combined joint manipulation and myofascial therapy. These patients received assessments at baseline, after 3 weeks of therapy, and 6 months after the completion of therapy. The primary outcomes were evaluated using visual analog pain scales and Roland-Morris activity scales.\n All four groups showed significant improvement in pain and activity scores after 3 weeks of care, but did not show further significant improvement at the 6-month follow-up assessment. No statistically significant between-group differences were found either at the 3-week or 6-month reassessments.\n For subacute low back pain, combined joint manipulation and myofascial therapy was as effective as joint manipulation or myofascial therapy alone. Additionally, back school was as effective as three manual treatments." ]	There is strong evidence that insoles are not effective for the prevention of back pain. The current evidence on insoles as treatment for low-back pain does not allow any conclusions. High quality trials are required for stronger conclusions.
CD009351	[ "12411035", "8001404", "8291726", "7926530", "4895338", "12663340", "19943458", "16443353", "11686419", "9603127", "9428538", "12050503", "7072998", "15581196", "16790607", "10890611" ]	[ "Clinical study on labor pain relief using the combined spinal-epidural analgesia and inhaling nitrous oxide.", "[Application of nitrous oxide in labor analgesia].", "Nitrous oxide in early labor. Safety and analgesic efficacy assessed by a double-blind, placebo-controlled study.", "Patient-administered nitrous oxide/oxygen inhalation provides effective sedation and analgesia for colonoscopy.", "Methoxyflurane and nitrous oxide as obstetric analgesics. I. A comparison by continuous administration.", "Dose-response characteristics during long-term inhalation of nitric oxide in patients with severe acute respiratory distress syndrome: a prospective, randomized, controlled study.", "Entonox for labor pain: a randomized placebo controlled trial.", "Effect of ciclesonide and fluticasone on exhaled nitric oxide in patients with mild allergic asthma.", "The effect of low-dose inhaled fluticasone propionate on exhaled nitric oxide in asthmatic patients and comparison with oral zafirlukast.", "Inhaled nitric oxide in acute respiratory distress syndrome: a pilot randomized controlled study.", "Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial. Inhaled Nitric Oxide in ARDS Study Group.", "Nitrous oxide (Entonox) inhalation and tolerance of transrectal ultrasound guided prostate biopsy: a double-blind randomized controlled study.", "Neonatal neurobehavioral effects of inhalation analgesia for vaginal delivery.", "Exhaled nitric oxide in bronchiectasis: the effects of inhaled corticosteroid therapy.", "A double-blind, randomized controlled trial on the use of a 50:50 mixture of nitrous oxide/oxygen in pain relief during suction evacuation for the first trimester pregnancy termination.", "Effect of inhaled nitric oxide on key mediators of the inflammatory response in patients with acute lung injury." ]	[ "To study the pain relief effectiveness of the combined spinal-epidural analgesia (CSEA) and the inhalation of nitrous oxide, and the influences on the mothers and infants.\n The 300 cases of pregnant women were randomly divided into 3 groups: CSEA group, nitrous oxide group and control group. The nitrous oxide group was that pregnant women inhaled nitrous oxide premixed with oxygen (50%:50%), the pregnant women of the CSEA group were injected fentanyl and bupivacaine in the subarachnoid and epidural space, analgesic was not used in the control group. The degree of labor pain, duration of the labor, way of delivery, bleeding volume, rate of anoxia of newborn, blood gas analysis to maternal radius artery and fetal umbilical blood among 3 groups were observed.\n The effect for analgesia labor of the CSEA group was much better than that of the nitrous oxide group (P < 0.01). In the first stage of labor and total stage of labor, the CSEA group was shorter than the others (P < 0.05), but there was no difference between the nitrous oxide group and the control group (P > 0.05). In the second stage of labor, the 3 groups were alike to each other. The bleeding volume of caesarean section (373 +/- 77) ml in the nitrous oxide group was much more than the other 2 groups, there was no difference between the CSEA group (259 +/- 78) ml and the control group (239 +/- 89) ml. The rate of obstetric forceps of CSEA group was higher than the control group (P < 0.01), and the rate of caesarean section of the nitrous oxide group was much higher than the CSEA group. The blood gas analysis to maternal radius artery and fetal umbilical blood and the rate of anoxia of newborn of 3 groups revealed no significant difference.\n The effectiveness of the combined spinal-epidural analgesia CSEA for analgesia labor is confirmed and has rarely side-effect, and it can be the first choice, and the inhalation of nitrous oxide can safely provide effective labor analgesia, too.", "Labor analgesia with nitrous oxide was studied in 34 parturients, and another 50 women taking no drug as the control group. The analgesic effect was satisfactory. By Mulleetr's pain in labor score, 91.18% women had score of 0-1, and their respiratory and circulatory functions were not affected. During inhalational analgesia the parturients remained conscious. Uterine contraction, progress of labor and neonatal Apgar score were not interferred, and postpartum bleeding was not increased. There was no complications in the treatment group. This study suggests that nitrous oxide with enough oxygen inhalation is one of the good drug for obstetric analgesia, but its concentration must be strictly controlled.", "Intermittent self-administered nitrous oxide has long had widespread use as an analgesic in labor, but its efficacy has not been adequately established. Questions about its effect on maternal oxygenation between labor contractions also have been raised.\n Twenty-six women were recruited to participate in a randomized, double-blind, cross-over, placebo-controlled study to assess the effect of intermittent nitrous oxide inhalation on labor pain and maternal hemoglobin oxygen saturation (SPO2) during the first stage of labor. Visual analog scale pain scores for each of five consecutive labor contractions were measured after administration of either nitrous oxide or compressed air.\n Mean visual analog scale pain scores for five contractions were 5.1, 5.2, 5.7, 5.2, and 5.6 (nitrous oxide) and 4.9, 5.2, 6.1, 5.6, and 5.7 (compressed air). There were no statistically significant differences in pain when nitrous oxide as compared with compressed air was administered. Pain scores did not differ significantly over time as a function of inhaled substance (F = 0.41, P = 0.53). The mean lowest SPO2 observed between these contractions after self-administration of nitrous oxide and air were 97, 97, 97, 97, and 97% (nitrous oxide) and 97, 96, 96, 96, and 96% (compressed air). SPO2 was significantly higher after nitrous oxide administration (F = 8.8, P = 0.007).\n While intermittent self-administered 50% nitrous oxide in oxygen does not appear to predispose parturient women to hemoglobin oxygen desaturation, its analgesic effect has yet to be clearly demonstrated.", "In a double-blind, randomized, placebo-controlled study of patients undergoing colonoscopy, sedation with an inhaled mixture of nitrous oxide/oxygen was compared with conventional intravenous sedation (pethidine 50 mg, midazolam 2.5 mg). In the patients studied, no significant differences were noted in number of pain episodes, need for additional intravenous sedation, or patient pain scores between the group receiving the nitrous oxide/oxygen mixture (n = 30) and those managed with conventional benzodiazepine/opiate injection (n = 29). Both methods were significantly more effective than placebo (n = 30). Six patients in the benzodiazepine/opiate group had oxygen desaturation, whereas none did in the nitrous oxide/oxygen group. Duration of stay after the procedure was significantly shorter in the gas inhalation group than in those receiving conventional intravenous sedation. Except for patients with severe chronic obstructive pulmonary disease, nitrous oxide/oxygen inhalation is a safe and acceptable alternative method of sedation and analgesia during colonoscopy.", "Methoxyflurane and nitrous oxide have been compared as obstetric analgesics. The inhaled concentrations of these agents, given continuously, were adjusted by an anaesthetist to maintain each patient at the optimum state between reaction to pain and consciousness. Assessments were made continuously.Though the anaesthetist's assessment showed no difference between the mean results, a greater proportion of the methoxyflurane patients were \"satisfactory\" for 90-100% of the time than of the nitrous oxide patients, particularly in regard to objective pain relief. The midwives' opinion of those who had \"complete\" pain relief supported this. Nausea was significantly less among methoxyflurane patients, and vomiting during labour occurred only in patients who had nitrous oxide. It is concluded that nitrous oxide and methoxyflurane given in a continuously adjusted concentration are almost equally effective as obstetric analgesics, though there are certain features which favour methoxyflurane.", "Inhaled nitric oxide (NO) improves systemic oxygenation (PaO2/FIO2) in adult patients with acute respiratory distress syndrome (ARDS). However, individual response varies, and previous trials demonstrated no outcome benefit. This prospective, randomized study in 40 ARDS patients analyzed dose-response (DR) characteristics during long-term inhaled NO. Patients were randomized for conventional therapy (control) or continuous treatment with 10 parts per million (ppm) inhaled NO until weaning was initiated. We measured DR curves of PaO2/FIO2 versus the inhaled NO dose at regular intervals. Before treatment (Day 0), peak improvement in PaO2/FIO2 was achieved at 10 ppm for both control and NO-treated patients. After 4 days, the DR curve of the NO-treated patients was left shifted with a peak response at 1 ppm. At higher doses (10 and 100 ppm), oxygenation deteriorated, and the response to inhaled NO disappeared in several patients. This effect was not observed in the control group. There was no effect of inhaled NO on duration of mechanical ventilation or stay at the intensive care unit. In conclusion, long-term inhaled NO with constant doses of 10 ppm leads to enhanced sensitivity after several days and does do not allow reduction of ventilation parameters. Hence, previous trials on therapy with inhaled NO in ARDS should be carefully interpreted, as they used constant NO concentrations, which may have become overdoses leading to deterioration of oxygenation after several days.", "This study aims to investigate the effectiveness of nitrous oxide on pain of labor contractions and on maternal SaO2. The patients were randomized to receive either a pre-prepared mixture of 50% nitrous oxide and oxygen or 50% oxygen by a coin. Study drugs started as early as the onset of pain with each contraction. The patient herself administered gases via a facemask connected to the uni-directional valve which enables the patients to breathe fresh gas in each inspiration. The gas administration was continued to the end of contraction pain at which the patient breathed the room air. Variables such as SaO2, blood pressure, pain and side effects were recorded. 534 ASA I and II parturients, aged from 16 to 35 years, scheduled for elective labor from September 2004 to 2006 were evaluated. Four patients were lost from the study. The mean age of patients was 25.5+/-4.3 years. During the first three measurements, the SaO2 was significantly higher in control group. In addition, the mean arterial pressure was comparable between groups except two first measurements in which the control group was higher. All the Visual Analogue Scale (VAS) values were significantly lower in nitrous oxide group. There were no significant differences in 1st and 5th min apgar scores between groups. All of the side effects were significantly higher among patients in nitrous oxide. In conclusion, our data indicate that using nitrous oxide 50% provides significant pain relief. Nonetheless, it is associated with few side effects, nitrous oxide can be quickly implemented during advanced painful labor.", "Ciclesonide is a novel, lung-activated, inhaled corticosteroid with once-daily efficacy and potent anti-inflammatory activity. The aim of the study was to compare the effect of ciclesonide and fluticasone propionate on exhaled nitric oxide (FENO), pulmonary function, and other parameters used in clinical evaluation of patients with mild allergic asthma. The study indicates that ciclesonide (in a daily dose of either 80 or 160 microg) induces both a faster and stronger decrease of FENO in comparison with fluticasone (100 microg twice daily). In both groups of patients treated with ciclesonide, the highest decrease in FENO levels was observed after 2 weeks of treatment. In the group of patients treated with fluticasone, this maximum effect was not observed till 8 weeks. An improvement in spirometric indices was observed in all groups studied. Statistical differences between the groups were not found; however, there was a trend toward higher increase in the group receiving 160 microg of ciclesonide. In all groups studied we observed clinical improvement (asthmatic symptoms and consumption of rescue medication were reduced), but there were no significant differences between these groups. Our results indicate that ciclesonide, compared with fluticasone, has stronger anti-inflammatory activity in patients with mild allergic asthma.", "Exhaled nitric oxide (ENO) is a noninvasive marker of ongoing inflammation in asthmatic patients. Comparison between inhaled and oral anti-inflammatory medications in reduction of ENO in asthmatic patients has not been performed.\n We measured changes in ENO, spirometry, need for rescue medication, quality of life (QOL), and diary scores (DS) after inhaled and oral anti-inflammatory therapy in adults with moderate asthma.\n A randomized, double-blind, placebo-controlled, crossover design with 4-week washout periods was used. A plateau level of ENO, measured in parts per billion (ppb), was obtained by chemiluminescence with a Sievers 280NOA as per American Thoracic Society recommendations. Eighteen asthmatic adults (15 Hispanic, with a percentage predicted forced expiratory volume in 1 second (FEV1%) of 50% to 85%) on bronchodilators (beta2) only were studied. Subjects used fluticasone propionate (FP) metered-does inhaler (44 microg), two puffs twice daily, and matching placebo (PB) for 4 weeks. Eight of the asthmatic patients (7 Hispanic, FEV1% 50% to 85%) on bronchodilators only then received blinded zafirlukast (ZK) 20 mg and matching PB twice daily for 4 weeks.\n Low-dose inhaled FP resulted in significant improvements in ENO, spirometry, QOL, DS, and beta2 use. A significant difference in mean ENO was found (P < 0.01) before and after FP from 34+/-7 ppb to 13+/-3 ppb. A significant improvement was found (P < 0.05) with FEV1% from 75+/-3 to 85+/-3 with FP treatment. The other measured parameters, percentage predicted of peak expiratory flow rate, beta2 need, DS, and QOL measurements, were improved with low-dose FP treatment. No significant reduction was found in ENO with oral ZK for 4 weeks. After oral ZK washout and the second extension arm of placebo, ENO significantly increased back to 47+/-14 ppb (P < 0.05), but spirometry measures did not worsen. Significant improvements were found with DS and beta2 use with oral ZK therapy.\n These results reveal ENO is reduced with only low-dose inhaled FP in asthmatic patients not on anti-inflammatory medication. In the smaller extension study, ENO was reduced with FP and not with oral ZK treatment, and ENO levels increased back to near prestudy levels after ZK washout and the second extension arm of placebo. As a marker of inflammation, ENO levels reveal an improvement with anti-inflammatory medication and worsening when it is discontinued.", "This pilot randomized controlled clinical trial of patients with ARDS was implemented to study the impact of inhaled nitric oxide (inhNO) on lung function, morbidity, and mortality. Thirty patients with ARDS were randomly allocated to usual care or usual care plus inhNO. The optimal dose of inhNO was determined to be between 0.5 and 40 parts-per-million daily. All therapeutic interventions were standardized. ARDS resulted mainly from sepsis (25 of the 30). During the first 24 h, the hypoxia score increased greatly in patients treated with inhNO +70.4 mm Hg (+59%) versus +14.2 mm Hg (+9.3%) for the control group (p = 0.02), venous admixture decreased from 25.7 to 15.2% in the inhNO group, and from only 19.4 to 14.9% in the control group (p = 0.05). After the first day of therapy no further beneficial effect of inhNO was detected. Forty percent of the patients treated with inhNO were alive and weaned from mechanical ventilation within 30 d after randomization compared with 33.3% in the control group (p = 0.83). The 30-d mortality rate was similar in the two groups; most deaths (11 of 17) were due to multiple organ dysfunction syndrome. This study shows that inhNO, in this population, may improve gas exchange but does not affect mortality.", "To evaluate the safety and physiologic response of inhaled nitric oxide (NO) in patients with acute respiratory distress syndrome (ARDS). In addition, the effect of various doses of inhaled NO on clinical outcome parameters was assessed.\n Prospective, multicenter, randomized, double-blind, placebo-controlled study.\n Intensive care units of 30 academic, teaching, and community hospitals in the United States.\n Patients with ARDS, as defined by the American-European Consensus Conference, were enrolled into the study if the onset of disease was within 72 hrs of randomization.\n Patients were randomized to receive placebo (nitrogen gas) or inhaled NO at concentrations of 1.25, 5, 20, 40, or 80 ppm.\n Acute increases in PaO2, decreases in mean pulmonary arterial pressure, intensity of mechanical ventilation, and oxygenation index were examined. Clinical outcomes examined were the dose effects of inhaled NO on mortality, the number of days alive and off mechanical ventilation, and the number of days alive after meeting oxygenation criteria for extubation. A total of 177 patients were enrolled over a 14-month period. An acute response to treatment gas, defined as a PaO2 increase > or =20%, was seen in 60% of the patients receiving inhaled NO with no significant differences between dose groups. Twenty-four percent of placebo patients also had an acute response to treatment gas during the first 4 hrs. The initial increase in oxygenation translated into a reduction in the FIO2 over the first day and in the intensity of mechanical ventilation over the first 4 days of treatment, as measured by the oxygenation index. There were no differences among the pooled inhaled NO groups and placebo with respect to mortality rate, the number of days alive and off mechanical ventilation, or the number of days alive after meeting oxygenation criteria for extubation. However, patients receiving 5 ppm inhaled NO showed an improvement in these parameters. In this dose group, the percentage of patients alive and off mechanical ventilation at day 28 (a post hoc analysis) was higher (62% vs. 44%) than the placebo group. There was no apparent difference in the number or type of adverse events reported among those patients receiving inhaled NO compared with placebo. Four patients had methemoglobin concentrations >5%. The mean inspired nitrogen dioxide concentration in inhaled NO patients was 1.5 ppm.\n From this placebo-controlled study, inhaled NO appears to be well tolerated in the population of ARDS patients studied. With mechanical ventilation held constant, inhaled NO is associated with a significant improvement in oxygenation compared with placebo over the first 4 hrs of treatment. An improvement in oxygenation index was observed over the first 4 days. Larger phase III studies are needed to ascertain if these acute physiologic improvements can lead to altered clinical outcome.", "We performed a randomized, placebo controlled double-blind trial to evaluate the effectiveness of Entonox (BOC Gases, Manchester, United Kingdom), that is 50% nitrous oxide and oxygen, as analgesia during transrectal ultrasound guided prostate biopsy.\n Patients referred for transrectal ultrasound guided prostate biopsy for the first time as an outpatient procedure were recruited subject to exclusion criteria and randomized to breathe Entonox or air via similar breath activated devices. At the end of the procedure patients completed a visual pain analog scale. Patients who refused study participation also completed the visual analog pain scale to assess the placebo effect of receiving gas through a mask.\n A total of 110 patients were studied. Statistical analysis using 1-way analysis of variance showed a highly significant difference in pain perception among the 3 groups (F [2,107] = 73.348, p <0.001). This significant decrease in pain was noted in the Entonox versus air and Entonox versus placebo groups. There was no significant difference in the air and placebo groups. Seven of the 51 patients receiving Entonox complained of feeling drowsy during the procedure, which resolved at completion of the procedure. In this group 49 patients would undergo this procedure again if needed. In 2 of the 45 patients in the group receiving air the procedure was abandoned due to pain, while another 19 would prefer more analgesia and 2 would prefer general anesthesia if the procedure was to be repeated.\n Our study shows that Entonox is a safe, rapidly acting and effective form of analgesia for the pain of prostate biopsy. We believe that it should be the analgesia of choice for this procedure.", "The authors studied the neonatal neurobehavioral effects of nitrous oxide:oxygen and enflurane:oxygen inhalation analgesia for vaginal delivery. Parturients were assigned randomly to receive no inhalation agent (Group 1, n = 21); enflurane, 0.3 to 0.8 per cent, and oxygen (Group 2, n = 22); or nitrous oxide, 30 to 50 per cent, and oxygen (Group 3, n = 18). Infants were tested at 15 min, 2 h, and 24 h of age using the Neurologic and Adaptive Capacity Score (NACS); and at 2 and 24 h using the Early Neonatal Neurobehavioral Scale (ENNS). No significant differences in neurobehavioral status occurred. For all groups, scores tended to be lowest at two hours of age. We conclude that neither enflurane nor nitrous oxide analgesia adversely affects neonatal neurobehavioral status at 15 min, 2 h, or 24 h of age.", "While exhaled nitric oxide (eNO) levels are reduced by inhaled corticosteroid therapy in asthma, such treatment effect is unclear in bronchiectasis.\n Stable non-smoking bronchiectasis patients were randomised to receive either fluticasone (1 mg/daily) or identical placebo via the Accuhaler device.\n Sixty non-smoking patients (38 women; mean age 56.4 +/- 12.7 years) were recruited. Of these, half received inhaled fluticasone and half placebo therapy. eNO was measured using a chemiluminescence analyser at 0, 4, 12, 24, 36 and 52 weeks. There was no significant difference in eNO levels between fluticasone and placebo patients over the study period. There was no correlation between baseline eNO with age, FEV1, FVC, 24 h sputum volume or number of bronchiectatic segments. Patients with Pseudomonas aeruginosa (PA) infection, but not their counterparts, displayed a correlation between 0- and 52-week eNO levels. PA infection was associated with significantly lower eNO levels among the patients.\n Inhaled fluticasone therapy, despite being an effective anti-inflammatory agent, has no significant effect on eNO production, either at individual time points or over the entire 52-week profile, in bronchiectasis. It appears that eNO might not reflect the extent of airway inflammation in bronchiectasis.", "This prospective study assessed the role of a 50:50 mixture of nitrous oxide (N2O) and oxygen for pain relief during the termination of first trimester pregnancies by suction evacuation under conscious sedation.\n Ninety women undergoing suction evacuation up to 12 weeks of gestation were randomized by a computer-generated randomization list and allocated using sealed envelopes to receive the N2O/O2 mixture or air during the operation. Pain scores during and after suction evacuation, post-operative side effects and satisfaction level were compared.\n No statistically significant differences in pain scores, post-operative side effects and satisfaction levels were found between the two groups.\n N2O/O2 did not reduce the pain level during suction evacuation for the first trimester pregnancy termination under conscious sedation.", "Inhaled nitric oxide is used to treat hypoxia associated with acute lung injury. Endogenous nitric oxide regulates inflammatory responses, but the effect of inhaled nitric oxide therapy is unknown. We hypothesized that inhaled nitric oxide may alter inflammatory responses and endogenous nitric oxide synthase activity.\n A randomized, prospective interventional study.\n A university hospital's general intensive care unit.\n Thirty-two patients with acute lung injury.\n Patients who responded to test doses of nitric oxide were randomized to ventilator therapy with and without inhaled nitric oxide. The inhaled concentration of nitric oxide was determined by dose titration at 0, 2, 10, and 40 ppm and the minimum concentration used, which resulted in an increase in the PaO2/FIO2 ratio of at least 25%.\n Patients were followed up for 30 days or until death, and bronchoalveolar lavage (BAL) was performed at 0, 24, and 72 hrs. Nitric oxide synthase activity was measured spectrophotometrically, and myeloperoxidase, elastase, interleukin-8, and leukotrienes were measured in BAL fluid by enzyme immunoassay. Total nitrite and lipid peroxides in serum were measured colorimetrically. Nitric oxide synthase activity decreased (p = .01) and total nitrite increased (p = .02) in patients receiving inhaled nitric oxide. Other markers of inflammation in BAL fluid did not change. Lipid peroxide concentrations also did not alter.\n The decrease in activity of nitric oxide synthase in patients receiving nitric oxide is likely to be the result of feedback inhibition of the enzyme. This study shows that inhaled nitric oxide has no effect on several markers of the inflammatory response system and does not lead to increased oxidant stress." ]	Inhaled analgesia appears to be effective in reducing pain intensity and in giving pain relief in labour. However, substantial heterogeneity was detected for pain intensity. Furthermore, nitrous oxide appears to result in more side effects compared with flurane derivatives. Flurane derivatives result in more drowsiness when compared with nitrous oxide. When inhaled analgesia is compared with no treatment or placebo, nitrous oxide appears to result in even more side effects such as nausea, vomiting, dizziness and drowsiness. There is no evidence for differences for any of the outcomes comparing one strength verus a different strength of inhaled analgesia, comparing different delivery systems or comparing inhaled analgesia with TENS.
CD005037	[ "1702663", "8971064" ]	[ "Intervention trial with selenium for the prevention of lung cancer among tin miners in Yunnan, China. A pilot study.", "Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group." ]	[ "This pilot study evaluated the feasibility and effectiveness of conducting a double-blind clinical trial for the prevention of lung cancer with selenium (Se) in Yunnan Tin Corporation, the People's Republic of China, where the incidence rates of lung cancer are extraordinarily high among the miners. Forty healthy miners were randomized to either 300 micrograms of Se in high Se malt cakes or an identical placebo of malt cakes daily for one year. Subjects consumed their usual daily diet. The low Se concentrations in plasma (0.05 +/- 0.008 microgram/mL) and hair (0.442 +/- 0.085 microgram/g) reflected their low dietary Se intake in the control subjects. In Se-supplemented group, the Se status was increased by 178% for serum and 194.8% for hair. The serum GSHpx activity was increased by 155.7%, whereas the lipid peroxide level was reduced by 74.5% compared to the placebo. The results of UDS assay indicated that the lymphocyte DNA damage induced by ultraviolet irradiation and carcinogen 3,4-benzpyrene could be protected by Se supplementation. Se-supplementation did not affect the liver function test (SGPT), as well as the concentrations of hemoglobin, albumin, and cholesterol. Thus, daily intake of 300 micrograms Se in form of Se-malt as a chemopreventive measure is safe and effective to humans with low Se status.", "To determine whether a nutritional supplement of selenium will decrease the incidence of cancer.\n A multicenter, double-blind, randomized, placebo-controlled cancer prevention trial.\n Seven dermatology clinics in the eastern United States.\n A total of 1312 patients (mean age, 63 years; range, 18-80 years) with a history of basal cell or squamous cell carcinomas of the skin were randomized from 1983 through 1991. Patients were treated for a mean (SD) of 4.5 (2.8) years and had a total follow-up of 6.4 (2.0) years.\n Oral administration of 200 microg of selenium per day or placebo.\n The primary end points for the trial were the incidences of basal and squamous cell carcinomas of the skin. The secondary end points, established in 1990, were all-cause mortality and total cancer mortality, total cancer incidence, and the incidences of lung, prostate, and colorectal cancers.\n After a total follow-up of 8271 person-years, selenium treatment did not significantly affect the incidence of basal cell or squamous cell skin cancer. There were 377 new cases of basal cell skin cancer among patients in the selenium group and 350 cases among the control group (relative risk [RR], 1.10; 95% confidence interval [CI], 0.95-1.28), and 218 new squamous cell skin cancers in the selenium group and 190 cases among the controls (RR, 1.14; 95% CI, 0.93-1.39). Analysis of secondary end points revealed that, compared with controls, patients treated with selenium had a nonsignificant reduction in all-cause mortality (108 deaths in the selenium group and 129 deaths in the control group [RR; 0.83; 95% CI, 0.63-1.08]) and significant reductions in total cancer mortality (29 deaths in the selenium treatment group and 57 deaths in controls [RR, 0.50; 95% CI, 0.31-0.80]), total cancer incidence (77 cancers in the selenium group and 119 in controls [RR, 0.63; 95% CI, 0.47-0.85]), and incidences of lung, colorectal, and prostate cancers. Primarily because of the apparent reductions in total cancer mortality and total cancer incidence in the selenium group, the blinded phase of the trial was stopped early. No cases of selenium toxicity occurred.\n Selenium treatment did not protect against development of basal or squamous cell carcinomas of the skin. However, results from secondary end-point analyses support the hypothesis that supplemental selenium may reduce the incidence of, and mortality from, carcinomas of several sites. These effects of selenium require confirmation in an independent trial of appropriate design before new public health recommendations regarding selenium supplementation can be made" ]	There is insufficient evidence at present that selenium supplementation alleviates the side effects of tumour specific chemotherapy or radiotherapy treatments or that it improves the after-effects of surgery, or improves quality-of-life in cancer patients or reduces secondary lymphoedema. To date, research findings do not provide a basis for any recommendation in favour or against selenium supplementation in cancer patients. Potential hazards of supplementing a trace mineral should be kept in mind. Since the last version of this review, the one new additional study has not provided information to change the conclusions of the original review.
CD002121	[ "15588465", "10783345", "14619648" ]	[ "Ovulation induction with urinary FSH or recombinant FSH in polycystic ovary syndrome patients: a prospective randomized analysis of cost-effectiveness.", "Induction of ovulation in women undergoing assisted reproductive techniques: recombinant human FSH (follitropin alpha) versus highly purified urinary FSH (urofollitropin HP).", "Recombinant FSH vs. urinary FSH for ovarian stimulation in in vitro fertilization." ]	[ "The aim of this prospective, randomized trial was to compare the clinical results and the cost-effectiveness of urinary FSH (uFSH) and recombinant FSH (rFSH) in ovarian stimulation for intrauterine insemination (IUI) cycles in polycystic ovary syndrome (PCOS) patients. One-hundred and seventy PCOS infertile patients undergoing IUI were enrolled, and protocols of ovarian stimulation with uFSH or rFSH were randomly assigned. The total number of cycles performed was 379 (182 and 197, respectively). The main outcome measures were the number of mature follicles, the days of stimulation, the number of ampoules and IU used per cycle, the biochemical/clinical pregnancy rates, the number of multiple pregnancies and the cost-effectiveness. No statistically significant differences were found in the follicular development, length of stimulation, pregnancy rates, delivery rates and multiple pregnancies between the two groups. In the uFSH group, the cost per cycle remained significantly lower (218.51 +/- 88.69 versus 312.22 +/- 118.12; P < 0.0001), even though a significantly higher number of IU of gonadotrophins were used (809.3 +/- 271.9 versus 589.1 +/- 244.7; P < 0.0001). The cost-effectiveness (i. e. within a group, the total cost of all cycles divided by no. of clinical pregnancies) was 1729.08 in the uFSH group and 3075.37 in the rFSH group. In conclusion, uFSH and rFSH demonstrated the same effectiveness in ovarian stimulation in IUI cycles in PCOS patients. The urinary preparation is more cost-effective due to the difference of its cost per IU.", "This multicentre, open, randomized, study compared the efficacy and safety of recombinant follicle stimulating hormone (rFSH; follitropin alpha) with highly purified urinary human FSH (uFSH; urofollitropin HP) in women undergoing ovulation induction for assisted reproductive techniques. Following long down-regulation with buserelin, patients received two ampoules of 75 IU (150 IU) s.c. rFSH or highly purified uFSH for 6 days, after which the dose could be increased until they fulfilled the criteria for human chorionic gonadotrophin (HCG) administration. Of 168 patients recruited, 155 received at least one dose of FSH, and 137 received HCG [68: rFSH (85%); 69: uFSH (92%)]. Following oocyte retrieval and fertilization, up to three embryos were replaced/patient and luteal support was given. The mean number of oocytes retrieved/patient was 10.2 +/- 6.0 for rFSH patients compared with 10.8 +/- 6.1 in the uFSH group (not significant). There was a trend towards fewer ampoules used (22.3 +/- 6.5 versus 24.3 +/- 6.5), higher pregnancy (44.3 versus 41.4%) and live birth rates (33.8 versus 26.7%), as well as a lower miscarriage rate (0.0 versus 16.7%) in favour of rFSH. However, no significant differences in efficacy parameters were recorded. Ovarian hyperstimulation syndrome occurred in 8.6% and 7.9% of rFSH and uFSH patients respectively. In conclusion, this protocol was effective in inducing multiple follicular development and high numbers of oocytes were retrieved with both drugs.", "To compare ovarian stimulation with recombinant FSH (rFSH) vs. urinary FSH (uFSH) in terms of hormonal events within ovarian follicles and the outcome of in vitro fertilization.\n A prospective randomized comparative study of rFSH (n = 70) vs. uFSH (n = 61) ovarian stimulation. Hormone determinations were serum estradiol (E2) on the day of human chorionic gonadotropin (hCG) administration, and E2, androstenedione (A) and testosterone (T) at the time of follicular aspiration in the follicular fluid and serum.\n The total dose of gonadotropins required and the length of ovarian stimulation were the same in the 2 groups. In follicular fluid the E2 and the A levels were significantly higher in the rFSH group (3,065 +/- 1,646 vs. 2,368 +/- 1,240 nmol/L, P = .004, and 103.7 +/- 51.6 vs. 89.0 +/- 42.3 nmol/L, P = .042, respectively), whereas A:E2 and T:E2 ratios were significantly lower (39.6 +/- 22.5 vs. 52.3 +/- 59.6, P = .042, and 9.1 +/- 4.7 vs. 17.6 +/- 26.9, P = .006, respectively). Serum hormonal levels, number of oocytes retrieved and pregnancy rates did not differ significantly between the groups.\n rFSH provides results similar to those of uFSH. rFSH enhances steroidogenesis and provokes different androgen/estrogen ratios than does uFSH without influencing the outcome of in vitro fertilization." ]	At this moment there are not sufficient data to determine which of rFSH or uFSH is preferable for ovulation induction in women with PCOS.
CD002278	[ "7005653", "2691402", "6365424", "2403486", "284065", "1890532", "6989549", "6754242", "6572128", "3060308", "1756217", "288179", "3476237", "342181", "11553111", "1059514", "4502245", "318958", "6593146", "281356", "356989", "12269458", "7822059", "3275147", "3475184", "4147708", "1623700", "3910338", "399995", "3465448", "270395", "6593805", "3895545", "12218280", "8783533", "6594021", "7004469", "6961143", "4865754", "9372795", "295702", "9835826", "4153291", "8448778", "8521431", "224083", "1057274", "6929082" ]	[ "[Cariostatic effect of Fluocaril; controlled clinical research].", "Clinical trial of a low-fluoride toothpaste for young children.", "Caries prevention using a 1.2% sodium monofluorophosphate dentifrice in an aluminium oxide trihydrate base.", "Caries-preventive effect of fluoride dentifrices with and without anticalculus agents: a 3-year controlled clinical trial.", "The caries-preventive effect of amine fluorides and inorganic fluorides in a mouthrinse or dentifrice after 30 months of use.", "Effectiveness of fortnightly tooth brushing with amine fluorides in caries-prone subjects.", "A 3-year clinical trial into the effect of fluoride content and toothpaste abrasivity on the caries inhibitory properties of a dentifrice.", "Comparative unsupervised clinical trial on caries inhibition effect of monofluorophosphate and amine fluoride dentifrices after 3 years in Strasbourg, France.", "Combined effects of a fluoride dentifrice and mouthrinse on the incidence of dental caries.", "A 3-year oral health dose-response study of sodium monofluorophosphate dentifrices with and without zinc citrate: anti-caries results.", "[The caries-protective efficacy of 2 fluoride varnishes in a 2-year controlled clinical trial].", "Effect of flouride varnish (Duraphat) treatment every six months compared with weekly mouthrinses with 0.2 per cent NaF solution on dental caries.", "Effect of fluoride containing dentifrice, mouthrinsing, and varnish on approximal dental caries in a 3-year clinical trial.", "Caries-preventive effect of two concentrations of stannous fluoride mouthrinse.", "Relative anti-caries efficacy of 1100, 1700, 2200, and 2800 ppm fluoride ion in a sodium fluoride dentifrice over 1 year.", "Caries preventive effect of a fluoride-containing varnish (Duraphat) after 1 year's study.", "[Prevention of dental caries by means of mouthwashes with 0.1 solutions of sodium fluoride. Results of a 2 year study].", "Effect of high-concentration ammonium and sodium fluoride rinses on dental caries in schoolchildren.", "Caries clinical trial of fluoride rinses in a Danish Public Child Dental Service.", "Observations on dental caries in primary teeth after frequent fluoride toplications in a program involving other preventives.", "A three-year clinical study to determine the separate and combined caries-inhibiting effects of sodium monofluorophosphate toothpaste and an acidulated phosphate-fluoride gel.", "A randomised controlled trial of the effectiveness of providing free fluoride toothpaste from the age of 12 months on reducing caries in 5-6 year old children.", "Enamel opacities and dental caries in children who used a low fluoride toothpaste between 2 and 5 years of age.", "[Reduction of dental caries after two years with a combination of mouthwashes and topical fluorides].", "Caries preventive effect of two fluoride varnishes and a fluoride mouthrinse.", "Caries prevention by daily fluoride mouthrinsing. Report of a three-year clinical trial.", "Caries development after termination of a fluoride rinsing program.", "Three-year caries increments after fluoride rinses or topical applications with a fluoride varnish.", "[Controlled clinical study of the caries prophylactic activity of a new bifluoride toothpaste (sodium monofluorophosphate + sodium fluoride)].", "Caries-preventive effect of Duraphat varnish applications versus fluoride mouthrinses: 5-year data.", "[Caries prevention by means of a Na2FPO3-toothpaste after 7 year's application].", "Three-year study of the effect of fluoride varnish (Duraphat) on proximal caries progression in teenagers.", "Effect on caries of different fluoride prophylactic programs in preschool children. A two year clinical study.", "A randomised controlled trial of the efficacy of supervised toothbrushing in high-caries-risk children.", "A comparative study of fluoride-releasing composite resin and glass ionomer materials used as fissure sealants.", "The caries-preventive effect of a fluoride varnish in the fissures of the first permanent molar.", "Caries prevention by dentifrices containing a combination of sodium monofluorophosphate and sodium fluoride. Report of a 3-year clinical trial.", "Caries-preventive effects of daily and weekly fluoride mouthrinsing in a fluoridated community: final results after 30 months.", "The caries-inhibiting effect of acidulated phosphate-fluoride chewable tablets: a two-year double-blind study.", "A three-year clinical trial of a combination of trimetaphosphate and sodium fluoride in silica toothpastes.", "Effect of fluoride varnish (Duraphat) in preschool children.", "Reversal of incipient and radiographic caries through the use of sodium and stannous fluoride dentifrices in a clinical trial.", "Caries-preventive effect of dentifrice containing 2percent sodium monofluorophosphate in a natural fluoride area in Denmark.", "Dental fluorosis, dental caries and fluoride exposure among 7-year-olds.", "Fluoride varnish versus acidulated phosphate fluoride gel: a 3-year clinical trial.", "The relative caries-inhibiting effects of a stannous fluoride dentifrice in a silica gel base.", "[Fluoride chewing tablets--a new aid in caries prevention. Comparative effect of a weekly mouthrinse with 0.2% NaF and daily chewing of a fluoride tablet (Gostrimant (R) ). 2. year clinical test in schoolchildren].", "Caries increment and gingival status during 2 years' use of chlorhexidine- and fluoride-containing dentifrices." ]	[ "A controlled, double-blind trial on 42 children showed that a dentrifrice containing 0,25% fluorine clearly prevented caries when used continuously for 2 years. This effects was greater than that of a similar toothpaste containing fluorine. Tolerance was excellent.", "In this double-blind trial, the anticaries effectiveness of a test toothpaste formulated for young children with 550 ppm F was compared with that of a positive control toothpaste containing 1055 ppm fluoride. More than 3000 2-year-old children were enrolled in the study and after 3 years of toothpaste use, 2177 (72 per cent) were examined. From a clinical and radiographic assessment, more than half the children were found to be caries free and only 32 (1.5 per cent) had evidence of rampant caries. There appeared to be little or no difference between children who had used test or control pastes, either in caries or in plaque levels. On the basis of this clinical trial the experimental toothpaste with 550 ppm fluoride would appear to have a similar anticaries efficacy to that of the control toothpaste. Differences were seen in relation to sex of the child and to social class. Girls had lower levels of plaque than boys but more carious teeth. Children from families in higher social classes had fewer carious teeth and lower levels of plaque.", "A 3-year clinical trial was carried out in France just after fluoride toothpaste was allowed to be sold on the mass market. The aim was to assess the caries preventive effect of a toothpaste containing the maximum fluoride level permitted by the EEC (1.2% SMFP). The trial started with 1318 10-12-yr-old children from a wide socioeconomic background in a typical French community. Test toothpaste was given to 659 children whereas the remaining 659 children obtained the same toothpaste without the fluoride additive. The brushing was unsupervised and performed by the children at home. Dental caries was assessed by clinical and radiographic examinations. 1061 children completed the trial. An interview carried out at the final examination identified a group of 116 uncooperative children (less than five brushings a week on average) who were not included in the statistical analysis. The following mean reductions were found: 26% for DMFT, 27% for DMFS, and 39% for DMFSU. The DMFS index for approximal, buccal-lingual and occlusal surfaces showed caries reductions of 32%, 25%, and 22%, respectively. The trial demonstrated a highly significant effectiveness of the 1.2% SMFP toothpaste in a French population.", "A 3-year, double-blind, randomized caries trial was conducted to evaluate the relative anticaries efficacy of four sodium fluoride dentifrices containing 250 ppm fluoride, 1,000 ppm fluoride in combination with 1% disodium 1-hydroxyethylidene-1.1-bisphosphonate (HEBP), and 1,000 ppm fluoride in combination with 1% disodium azacycloheptylidene-2.2-bisphosphonate (AHBP). As a positive control, a monofluorophosphate dentifrice (1,000 ppm fluoride) was used. At outset 1,161 Icelandic children, 11 and 12 years of age, were randomly assigned to one of the five treatment groups and 1,035 subjects completed the trial. After 3 years of unsupervised brushing, the dentifrice containing 250 ppm fluoride was significantly less effective in controlling the caries increment. The combination of sodium fluoride and AHBP was significantly more effective than the positive control.", "The study groups using a dentifrice and mouthrinse both containing fluorides, a dentifrice containing stannous fluoride and a mouthrinse containing sodium fluoride, or a mouthrinse containing sodium fluoride with a placebo dentifrice had a 20.7% to 29.0% lower DMF increment than the control group after 30 months. These differences were significant. The study groups using a dentifrice containing amine fluorides and a placebo mouthrinse, a mouthrinse containing amine fluorides and a placebo dentifrice, or a dentifrice containing stannous fluoride and a placebo mouthrinse had a 13.6% to 22.4% lower DMF increment than the control group. These differences were not statistically significant. There was no significant difference in effectiveness against caries between the use of the organic or inorganic fluoride products.", "The aim of this study was to assess the caries incidence and plaque accumulation in schoolchildren at caries risk, after brushing the teeth fortnightly with gels containing 0, 0.4% F, 1.25% F as amine fluoride (AmF) or the common amine fluoride toothpaste containing 0.125% F. The study was conducted double blind over an 18-month period, and after 6 months discontinuation of brushing. Only the group that brushed with the 1.25% AmF gel showed a significant decrease in caries development compared to the group that brushed with the 0.125% AmF toothpaste. During the 6-month discontinuation period, the incidence of caries increased in all groups; the differences in caries development between all groups were not significant. Plaque indices were significantly lower in the AmF-treated groups. The highest fluoride concentration in the gel reduced the development of caries to zero, probably due to increased fluoride levels in the oral milieu of caries risk children. In order to maintain a positive effect of fluoride over an extended time period, caries-prone subjects should continue an initiated fluoride programme.", "The effect of reducing the abrasivity of toothpaste on dental caries was observed in a 3-year clinical trial involving 1106 11-13-year-old Berkshire schoolchildren were divided into three groups; Group 1 were allocated a low abrasivity paste containing 0.8% sodium monofluorophosphate, Group 2 a paste of conventional abrasivity also containing 0.8% sodium monofluorophosphate and Group 3 a low abrasivity non-fluoride paste. After 3 years the net DMFS increments (clinical and radiographic scores combined) were 4.22 in Group 1, 4.72 in Group 2 and 6.43 in Group 3. The differences between Groups 1 and 3 and between Groups 2 and 3 were highly significant (P less than 0.001). The mean increment in Group 1 was lower than in Group 2 but did not reach statistical significance. Reducing the abrasivity of the toothpaste had no meaningful effect on the standard of oral hygiene and prevalence of gingivitis as measured by the Gingival and Plaque Indices.", "A randomized, double blind clinical trial of the caries inhibition effects of dentifrices containing respectively monofluorophosphate and amine fluoride was performed. A third control group used a toothpaste without fluoride. A total number of 2008 schoolchildren ranging in age from 6 to 8 years and living in Strasbourg (France) participated in this study. After a baseline examination three groups were constructed with the block randomization technic. The caries inhibition effects of the three dental pastes were compared after 3 years of unsupervised use. The monofluorophosphate dentifrice showed a reduction of 7.02% for DMFT, 5.17% for DMFS and 25.26% for the df rate. The reduction of amine fluoride dentifrice caries was respectively 21.62% for DMFT, 20.94% for DMFS and 48.66% for the df rate.", "751 14- and 15-year old children completed a 3-year, double-blind, caries preventive program. The effects of daily, supervised toothbrushing with an 0.76% sodium monofluorophosphate dentifrice, rinsing with a 0.05% sodium fluoride mouthrinse, and the combined effects of the two treatments were investigated. Both the dentifrice and mouthrinse reduced the incidence of dental caries, but their combined use at the same time had no greater effect than either used alone.", "A 3-yr clinical trial has been conducted on 3000 12-yr-old children in Lanarkshire, Scotland, with the aim of investigating the effects on oral health of toothpastes containing both sodium monofluorophosphate and zinc citrate, the former being present at fluoride levels of 1000, 1500, and 2500 ppm F. No significant difference in caries increments was found between the group of children using toothpastes incorporating zinc citrate and their counterparts using zinc-free pastes. However, a significant anti-caries dose-response was demonstrated over the SMFP range used. This dose-response was evident for boys and girls and also for the various types of teeth and tooth surfaces.", "The aim of this randomized, double-blind study was to measure the cariostatic effect of Bifluorid 12 (VOCO GmbH), containing 6% sodium fluoride and 6% calcium fluoride and Laweflour-Schüttellack (LAW), containing 5% sodium fluoride in comparing of placebo varnish. The caries study included 400 schoolchildren, aged 12-14 years. The tests according to the DMFS were carried out by two independent examiners. The 400 children were divided into 3 test and 1 placebo group, each group consisting of 100 subjects. After two years there was a significant inhibition of caries increment in all test groups compared to placebo group. Percentage caries reduction ranged from 25 to 30%. The highest effect was stated at proximal surfaces.", "Recent studies have shown a high fluorine uptake in the enamel and a considerable caries reduction following the application of varnished containing fluoride. As the application is easy to carry out it may in certain situations serve as an alternative to other topical fluoride school programmes. The aim of the present study, therefore, was to compare the caries increment in schoolchildren exposed to a fluoride varnish (Duraphat) every six months and in children receiving the conventional weekly fluoride mouthrinsing programme with 0.2 per cent sodium fluoride over a two-year period. Two hundred 14-year-old children, divided into one test and one control group took part in the study. They were clinically and radiographically examined every year. Preexperimental data revealed no differences between the groups. During the experimental period the children in the fluoride varnish group developed a statistically significant lower number of new carious lesions compared with those in the mouthrinsing group. The difference in caries increment was about 30 per cent. Further clinical studies to compare the effects of various topical fluoride programmes are recommended.", "The purpose of this study was to evaluate the separate effect of fluoride dentifrice, fluoride mouthrinsing and fluoride varnish on approximal dental caries. All 252 13-14-yr-old children at an elementary school were selected at random and divided among four groups for a 3-yr longitudinal study. Group 1 received a fluoride dentifrice for home care and a fluoride mouthrinse once a week. Group 2 received a fluoride dentifrice for home care and a placebo mouthrinse once a week. Group 3 received a fluoride dentifrice for home care and a fluoride varnish once every 3 months. Group 4 received a placebo dentifrice for home care and a fluoride rinse once a week. Fluoride rinsing did not give any additional effect compared with placebo-rinsing when a fluoride dentifrice was used for home care. Fluoride varnish gave a significant caries reduction compared with fluoride rinsing.", "The effectiveness of a stannous fluoride mouthrinse, when used once each school day, was investigated in a 3-year study. Effervescent stannous fluoride tablets of two concentrations were dissolved in 20 ml of water, giving solutions of 100 parts/10(6)F- and 200 parts/10(6)F- respectively. Approximately 1,200 children, with a mean age of 10 years, were divided on a random basis into three groups. Two of the groups rinsed with the two strengths of solution and the third group rinsed with a placebo. Examinations were carried out at the commencement of the study, and at yearly intervals thereafter. The final series was carried out a year after the rinsing procedures were terminated. There were significant reductions in the numbers of new caries in each of the two experimental groups as compared with the controls. The concentration of the solutions appeared to have little influence on the results. More dramatic reductions were noted in the teeth which erupted during the course of the study. A residual effect was demonstrated a year after the rinsing procedures were terminated.", "There is limited evidence from clinical trials on the dose response of sodium fluoride dentifrices at concentrations above 1100 ppm fluoride ion, with respect to caries efficacy. This randomized, double-blind study examined the anti-caries effectiveness of sodium fluoride dentifrices containing 1700 ppm, 2200 ppm and 2800 ppm fluoride ion relative to an 1100 ppm fluoride ion control. A population of 5439 elementary schoolchildren, aged 6-15 years, was recruited from an urban central Ohio area with a low fluoride content water supply (<0.3 ppm). Subjects were examined by visual-tactile and radiographic examination at baseline and after 1, 2, and 3 years of using the sodium fluoride dentifrices. Subjects were stratified according to gender, age and baseline DMFS scores derived from the visual-tactile baseline examination and randomly assigned to one of four treatment groups: 0.243% sodium fluoride (1100 ppm fluoride ion), 0.376% sodium fluoride (1700 ppm fluoride ion), 0.486% sodium fluoride (2200 ppm fluoride ion), and 0.619% sodium fluoride (2800 ppm fluoride ion). All products were formulated with the same fluoride compatible silica abrasive. Results after 1 year provided evidence of a positive sodium fluoride dose response. Compared to the 1100 ppm fluoride treatment group, the 1700 ppm fluoride treatment group had an 11.0% reduction in DMFS that was not statistically significant, while the 2200 ppm and 2800 ppm fluoride treatment groups showed statistically significant (P<0.05) reductions of 18.6% and 20.4%, respectively. The reductions in caries delivered by the higher fluoride dentifrices were present across all tooth surface types, but were most pronounced for occlusal surfaces. Results at years 2 and 3 were confounded by a concurrent fluoride rinse program, which involved portions of the study population. While the trends for the higher fluoride dentifrices observed at year 1 remained at years 2 and 3, the difference observed between treatments were substantially less and failed to reach statistical significance (P<0.05). Collectively, the data demonstrate that the 2200 ppm and the 2800 ppm fluoride treatments delivered statistically significantly greater caries efficacy than the 1100 ppm fluoride treatment. This large-scale clinical trial provides evidence of a positive statistically significant dose relationship between dental caries and sodium fluoride in a dentifrice at levels above 1100 ppm fluoride at year 1.", "The caries prophylactic effect of semi-annual applications of a fluoride-containing varnish (Duraphat) was tested in 121 15-year-old children. The children were divided into a test (60 subjects). The teeth of the children in the test group were coated with fluoride varnish at the beginning of the experimental period and again 6 months later. A clinical and radiographic examination of all children was performed immediately prior to the first application of varnish and 1 year later. The mean caries increment was 0.9 new DMFS in the test group and 4.0 in the control group. The difference was statistically significant at the 0.1% level. The caries prophylactic effect on different tooth surfaces was statistically significant both on proximal and on occlusal surfaces at the 0.1% level. Analyzing the material with respect to the caries prophylactic effect against the background of caries prevalence at the start of the investigation showed a better effect in the group of children with low and medium initial DMFS values.", "nan", "A double-blind clinical trial was conducted in a non-fluoridated community to determine the effect on enamel fluoride and caries experience of daily rinsing in school with 1,000 parts/10(6) solutions of ammonium fluoride or sodium fluoride at pH 4.4. Subjects were 10- to 12-year-old children (n approximately equal to 200/group at baseline), about one-half of whom reported the usage of fluoride supplements. Dental caries (DFS index) and enamel fluoride (in vivo biopsy) were evaluated at baseline, 12 months, and 24 months. Supplement users had higher enamel fluoride levels and less caries experience initially, as well as generally lower caries increments over the study. In year 1, the overall caries reductions (supplement users and non-users combined) were 23 % (ammonium fluoride) and 33 % (sodium fluoride), P less than 0.01. For year 2, treatment effects were significantly greater: 54 % (ammonium fluoride) and 47 % (sodium fluoride). In newly erupted teeth, the effects of the ammonium fluoride (70 % DFS reduction) was significantly greater (P = 0.013) than that of the sodium fluoride (48 % DFS reduction). Enamel fluoride levels at the end of 2 years were 3,124 parts/10(6) (ammonium fluoride), 2,771 parts/10(6) (sodium fluoride), and 2,603 parts/10(6) (placebo), P = 0.025.", "365 2nd through 4th graders completed a 3-yr clinical trial on the caries-preventive effect of rinsings every second week during the school year with 10 ml of an 0.2% neutral solution of sodium fluoride. All children received regular dental examinations and treatment in clinics established by the municipality in which the study took place. The trial was performed under double-blind conditions. The caries increment on teeth erupted at baseline was 1.75 DMFS in the fluoride group and 1.83 DMFS in the placebo group (P greater than 0.05; 95% confidence limits for percentage caries reduction: -20.7% and 29.5%). The caries increment on teeth erupting during the trial was 0.73 DMFS in the fluoride group and 0.99 DMFS in the placebo group (P greater than 0.05; 95% confidence limits for percentage caries reduction: 1.0% and 51.6%).", "The anticaries effect of repeated toplications with APF gel was assessed in the primary dentition of 2-6-year-olds after 8, 18 and 28 months. Frequent, but less than daily, topical fluoride therapy appeared to have little effect in pre-school children consuming water-borne fluoride and receiving other traditionally recommended modalities of prevention.", "nan", "To assess the impact of regularly supplying free fluoride toothpaste regularly to children, initially aged 12 months, and living in deprived areas of the north west of England on the level of caries in the deciduous dentition at 5-6 years of age. A further aim was to compare the effectiveness of a programme using a toothpaste containing 440 ppmF (Colgate 0-6 Gel) with one containing 1,450 ppmF (Colgate Great Regular Flavour) in reducing caries.\n Randomised controlled parallel group clinical trial. Clinical data were collected from test and control groups when the children were 5-6 years old.\n A programme of posting toothpaste with dental health messages to the homes of children initially aged 12 months. Clinical examinations took place in primary schools.\n 7,422 children born in 3-month birth cohorts living in high caries areas in nine health districts in north west England. Within each district children were randomly assigned to test or control groups.\n Toothpaste, containing either 440 ppmF or 1450 ppmF, and dental health literature posted at three monthly intervals to children in test groups until they were aged 5-6 years.\n The dmft index, missing teeth and the prevalence of caries experience.\n An analysis of 3,731 children who were examined and remained in the programme showed the mean dmft to be 2.15 for the group who had received 1,450 ppmF toothpaste and 2.49 for the 440 ppmF group. The mean dmft for the control group was 2.57. This 16% reduction between the 1,450 ppmF and control group was statistically significant (P<0.05). The difference between the 440 ppmF group and control was not significant. Further analyses to estimate the population effect of the programme also confirmed this relationship.\n This study demonstrates that a programme distributing free toothpaste containing 1,450 ppmF provides a significant clinical benefit for high caries risk children living in deprived, non-fluoridated districts.", "A recent clinical trial investigated the cariostatic effectiveness of a low (550 ppm) fluoride toothpaste in comparison with a standard (1050 ppm) control paste in pre-school children who were 2-years-old at the start of the 3-year trial. The present study has investigated the prevalence of enamel opacities in permanent incisor teeth and of caries in children who had taken part. As well as children from test and control groups, a third group of non-trial children were included in the sample. A total of 1,523 children were examined in schools and had photographs taken of their upper permanent incisor teeth. The latter were scored using the Thylstrup and Fejerskov (TF) index for fluorosis and the modified Developmental Defects of Enamel (DDE) index. Differences between the groups were small in real terms but using the TF index the child and tooth prevalence of opacities were significantly lower in the children who had used the test paste with a lower fluoride content; the same trend was seen in diffuse defects scored using the modified DDE index. There was no significant difference in the prevalence of caries in either primary or permanent teeth although the trend in both cases was for slightly more disease in children who had used the test paste.", "The study's purpose was to evaluate the reduction of dental caries incidence by the association of two preventive methods. 246 students of both sexes aged from 7 to 11 years registered in \"Escola de Educação Básica da Universidade Federal de Uberlândia\" and living in the urbana area of Uberlândia, state of Minas Gerais, were examined. The sample was distributed into two groups: children from Group 1, which received a semestral topical application of Acidulated Fluor Phosphate at 1.23% and children from Group II, that besides the topical application above related (Group I) also received weekly mouthwashes of sodium fluoride aquesus solution at 0.2%. After two years of study DMFS index were tabled and statistically analysed. It was verified a reduction of 33.97% in the incidence of dental caries (in the permanent dentition). The difference between the Groups was significant at 5% level of confidence.", "nan", "nan", "In a municipality near Copenhagen, Denmark, where fortnightly fluoride rinses with 0.2% neutral sodium fluoride had been performed for more than a decade, 1306 children from kindergarten through 6th grade were stratified by school and grade and randomly distributed into two groups. One group continued the fluoride rinses, the other group had the fluoride solution replaced with distilled water. Both solutions were slightly flavored. 1083 children completed the 3-yr trial. Caries was recorded clinically by the dentists in the municipal dental service using the diagnostic criteria for the Child Dental Health Services, and on bitewing radiographs by one of the authors applying the criteria developed by GRONDAHL et al. Permanent molars and premolars were included in the study. Clinically, caries increment in the two groups was the same with pits and fissures containing 94% of the DMFS. According to the radiographs, caries progression in the water group was higher than in the fluoride group. This difference was statistically significant for the surfaces erupting during the study (P less than 0.05).", "251 9-12-yr-old children completed a 3-yr, double-blind, clinical trial of two caries preventive fluoride programs. Caries increments and progression patterns were compared in two groups of children who rinsed every fortnight with a 0.2% NaF solution or received biannual topical applications with a fluoride varnish (Fluor-Protector). Clinically recorded mean DFS increments were 3.3 +/- 0.2 (SE) in the rinse group and 3.5 +/- 0.2 in the varnish group. In both groups nearly half of these increments were recorded in the occlusal surfaces of second molars. The mean incremental DFS recorded radiographically on approximal surfaces of posterior teeth were 1.1 +/- 0.2 and 1.5 +/- 0.2 in the rinse and varnish group, respectively. None of the inter-group differences were statistically significant (P greater than 0.05). Detailed analyses of the radiographic scores revealed a similar and extremely slow caries progression in the two study groups and they strengthened the conclusion of equal clinical efficacy of the two treatments. None of the fluoride programs had been able to change preestablished patterns of caries development among the children.", "nan", "nan", "After 7 years unsupervised use of a Na2FPO3 paste the number of new DMF-surfaces was 36 to 38% lower than in the control group. The caries-inhibiting effect is statistically significant (P less than 0.001). Separate consideration of the first molar reduced caries of the other teeth to 40--42%.", "The effect of sodium fluoride varnish (Duraphat) applications on proximal caries progression was studied during a 3-yr period in 87 teenagers and compared to a control group (n = 107). In the fluoride varnish group the children were treated with fluoride varnish every third month during the experimental period. Caries lesions on the mesial surfaces of first premolars to the mesial surfaces of second molars were recorded annually on radiographs and an individual progression value was calculated. The study showed that topical application of fluoride varnish every third month significantly (P less than 0.05) reduced the progression of proximal caries lesions in premolars and molars. The most obvious reduction of caries progression was observed among children who developed between two and eight new proximal lesions during the test period. In the children with the highest caries activity (greater than nine new proximal lesions) Duraphat treatments did not significantly reduce proximal caries progression in premolars and molars.", "376 three-year old children were divided into four experimental groups and exposed to different combinations of preventive programs for a period of two years. All the groups were given the same basic prophylactic information. Additionally Group I received fluoride tablets (FLUDENT) for daily sucking twice a day plus a placebo dentifrice free of fluoride. Group II was given a fluoride dentifrice containing 0.025% F, (ACTA). Group III was given a placebo dentifrice plus fluoride varnish (Duraphat) twice a year. Group IV a fluoride dentifrice containing 0.025% F (ACTA) plus fluoride varnish (Duraphat) twice a year. No statistically significant difference in caries increment during the two experimental years was found between the groups. A tendency to lower caries increment was found in Group IV, i.e. in the children using the low fluoride dentifrice and treated twice a year with fluoride varnish.", "Scottish children have one of the highest levels of caries experience in Europe. Only 33% of 5-year-old children in Dundee who developed caries in their first permanent molars by 7 brushed their teeth twice a day. High-caries-risk children should benefit if they brush more often with fluoridated toothpaste. The aim of this clinical trial was to determine the reduction in 2-year caries increment that can be achieved by daily supervised toothbrushing on school-days with a toothpaste containing 1,000 ppm fluoride (as sodium monofluorophosphate) and 0.13% calcium glycerophosphate, combined with recommended daily home use, compared to a control group involving no intervention other than 6-monthly clinical examinations. Five hundred and thirty-four children, mean age 5.3, in schools in deprived areas of Tayside were recruited. Each school had two parallel classes, one randomly selected to be the brushing class and the other, the control. Local mothers were trained as toothbrushing supervisors. Children brushed on school-days and received home supplies. A single examiner undertook 6-monthly examinations recording plaque, caries (D(1) level), and used FOTI to supplement the visual caries examination. For children in the brushing classes, the 2-year mean caries increment on first permanent molars was 0.81 at D(1) and 0.21 at D(3) compared to 1.19 and 0.48 for children in the control classes (significant reductions of 32% at D(1) and 56% at D(3)). In conclusion, high-caries-risk children have been shown to have significantly less caries after participating in a supervised toothbrushing programme with a fluoridated toothpaste.\n Copyright 2002 S. Karger AG, Basel", "The objectives of the study were to investigate the clinical use of two fluoride-releasing fissure sealants and to study fluoride release under laboratory conditions.\n In the clinical part of the study the two materials, FluroShield and Baseline, were applied to matched contralateral caries-free first permanent molars in 86 children aged 7-8 years. In the laboratory study fluoride release from each material was measured using a model cavity system.\n After 3 years FluroShield was intact on 70% of teeth. Retention was significantly better on lower molars than upper molars. Baseline was lost from all except two teeth within 6 months. After 3 years, caries had affected four teeth sealed with FluroShield and 24 teeth sealed with Baseline; this difference was highly significant. The laboratory study showed that FluroShield released twice as much fluoride over 9 days than did Baseline. Long term studies using FluroShield showed a small steady fluoride release over 6 months.\n The conclusion of the study was that FluroShield was a much more effective fissure sealant than Baseline. The clinical performance of FluroShield was comparable to that of other inert composite resin sealants and superior to that of fluoride-releasing sealants used previously.", "The aim of the present study was to assess the caries-preventive effect of topical application of Duraphat on the occlusal surface of newly erupted first permanent molars. A base-line examination was performed on children aged 5 years and 9 months. The children were randomly divided into a Duraphat group and a control group. In accordance with the anatomy of the fissure system, the molars were divided into shallow and deep fissures, respectively. From the time of eruption, 381 molars were examined every 3rd month during 24 months. Duraphat was applied every 6th month, altogether four times. The results showed that in the Duraphat group 35% of the fissures were decayed compared with 80% in the control group. Caries reduction amounted to 56%, and the caries-preventive effect was found in molars with shallow and deep fissures.", "nan", "nan", "nan", "The relative efficacy of NaF silica toothpastes containing 1000 ppm fluoride and 1500 ppm fluoride in the control of dental caries is not clear-cut. Also, it has not been established that incorporation of trimetaphosphate (TMP) improves the anticaries activity of NaF toothpastes. A three-year clinical trial was conducted to test the hypotheses that: (i) the anticaries activity of NaF toothpastes containing 1500 ppm F was greater than that of NaF toothpastes containing 1000 ppm F, and (ii) inclusion of TMP improved the efficacy of NaF silica pastes. Subsidiary aims included determination of whether frequency of toothbrushing and method of rinsing after brushing were correlated with caries increments. The study involved 4196 children aged 11 to 12 years at outset. These participants had been selected from a pool of 7374 potential subjects on the basis of caries experience and dental eruption pattern. They were stratified by sex, examiner, and presence of calculus and caries, and were allocated at random to one of the four toothpastes under study. Using mirror and probe and also FOTI, we carried out clinical examinations at baseline and annually thereafter for 3 yrs. Bitewing radiographs of a subset of children were taken at baseline and at the end of the study. The outcome measure for the study, DMFS increment, was defined as the increase in caries over 3 yrs, taking into account changes occurring on individual tooth surfaces. Data for 3467 subjects were available for analyses at both baseline and year 3 examinations. Radiographs were taken for 1942 subjects at both baseline and year 3 examinations. The mean three-year clinical-only DMFS increment for the subjects using 1500-ppm-NaF pastes was 3.93, which was 6% lower than the corresponding mean of 4.19 for the 1000-ppm-NaF pastes. There was no significant difference between the mean DMFS increment for those using paste with or without TMP. Subjects who claimed to brush more frequently or who claimed not to use a tumbler to rinse after toothbrushing had lower three-year DFMS increments.", "The caries-preventive effect of semiannual applications of a fluoride varnish (Duraphat) was tested for 2 years in 225 3-year-old children; 113 children served as a control group. At the baseline examination, 69% of the children in the test group and 75% in the control group were caries-free. The results after 2 years showed an average caries increment of 2.1 surfaces in the test group and 3.7 in the control group. The difference is statistically significant. Thirty-eight percent of the children in the test group and 27% in the control group were still caries-free. The caries reduction was 44%.", "Experimental evidence has clearly demonstrated that the early stages of lesion formation (enamel demineralization) are reversible following exposure to saliva and/or fluoride. Clinical evidence for remineralization has also been reported extensively in the literature. However, the literature is lacking with respect to data from well-controlled clinical studies regarding the quantitative contribution of remineralization to arrestment and reversal of caries. Retrospective analysis of an existing clinical trial database provided an opportunity to examine the incidence of clinical lesion reversals in a placebo-controlled, double-blinded caries clinical study. The clinical study examined three treatment groups: 1) 0.243% sodium fluoride/silica dentifrice, 2) 0.4% stannous fluoride/calcium pyrophosphate (positive control) dentifrice and 3) non-fluoridated placebo/calcium pyrophosphate (negative control) dentifrice. Clinical measures in this study included both radiographic and visual-tactile assessments of caries. Examination of all subjects revealed a statistically greater frequency for caries reversals in the sodium fluoride group as compared to the placebo group at Year 3, for both total and radiographic caries. In contrast, while caries reversals in the stannous fluoride group occurred with greater frequency than in the placebo group at Year 3, for both total and radiographic caries, the differences were not statistically significant. When only subjects who were \"at risk\" for potential reversals (i.e., those with a minimum of one carious lesion at baseline) were examined, a statistically greater frequency in caries reversals was observed in both the sodium fluoride (total, incipient, and radiographic caries) and stannous fluoride (total and radiographic caries) groups as compared to the placebo group at Year 3. Collectively, these data confirm the ability of both 0.243% sodium fluoride/silica and 0.4% stannous fluoride/calcium pyrophosphate dentifrices to clinically reverse caries. The results suggest that sodium fluoride may deliver a greater frequency of caries reversals than stannous fluoride, although these treatments were not found to be significantly different.", "nan", "Mild dental fluorosis is frequently linked to fluoridated water, but discretionary fluoride sources may also be important. The aim of this study was to record age of weaning and fluoride exposure from water, toothpaste and supplements, and to relate these to the presence of caries and fluorosis in children born in 1983. In Perth (Western Australia) 14 school classes were selected. The 350 children (mean age 7.5 years) ultimately included gave fluoride exposure data for the period birth to 4 years of age. Caries (DMFT, WHO criteria, no radiographs) and dental fluorosis (TF index, dry permanent incisors) were registered clinically. Most (89%) children had lived at least 2.5 years in a fluoridated area. Supplement use was minimal and unrelated to caries or fluorosis. Mean age of weaning of those who had been breast-fed was 7.7 months; by 9 months, 74% had been weaned. Eighty-five percent liked toothpaste, 60.7% had swallowed it, and the mean age of starting to use it was 1.5 (SD 0.96) years. Caries prevalence was 0.1 and mean DMFT was 0.13. The prevalence of fluorosis was 0.48; 63% of fluorosis was TF score 1. Residence in a fluoridated area for > or = 2.5 of the first 4 years of life had an odds ratio (OR) of 4.9 for fluorosis. Weaning before 9 months of age, swallowing toothpaste and liking toothpaste were also statistically significant risk factors. Major risk factors for more severe fluorosis (TF > or = 2) were early weaning and swallowing toothpaste (ORs 2.77 and 2.64, respectively). Residence in a fluoridated area (OR 2.2) was not a statistically significant risk factor.(ABSTRACT TRUNCATED AT 250 WORDS)", "The aim of this trial was to compare the caries-preventive effect of sodium fluoride varnish and acidulated phosphate fluoride (APF) gel. A total of 254 children aged 12-13 years with high past caries experience were randomly divided into two groups. The participants received semi-annual applications of either fluoride varnish or APF gel for 3 years. During the study, the mean (+/- SD) total DMFS increments of the varnish and gel groups were 6.8 +/- 5.6 and 7.7 +/- 6.4, respectively, when initial caries was included, and 3.1 +/- 3.7 and 3.6 +/- 4.6 when initial caries was excluded. The difference was most evident on the approximal surfaces (varnish: 1.4 +/- 2.4; gel: 1.9 +/- 3.1). However, this difference was not statistically significant. Although larger studies are needed for firm conclusions about the comparative effect of the two fluoride measures, the results suggest that fluoride varnish is as effective as fluoride gel at least in preventing approximal caries. Taking into account the shorter treatment time, using fluoride varnish for professional applications seems justified.", "An unsupervised toothbrushing study involving 1,339 children from 5 to 13 years of age conducted for three years compared two stannous fluoride dentifrices, one in a calcium pyrophosphate base and the other in a silica gel base, with a nonfluoride control dentifrice. The test dentifrice, stannous fluoride in a silica gel base, reduced caries to a significant extent when compared with the nonfluoride control dentifrice.The percentage of reductions ranged from 15% to 25% for whole mouth and interproximal surface indexes. There was no significant difference between the two fluoride dentifrices.", "nan", "A total of 91 schoolchildren, 13 years of age, were distributed into three groups. Three test dentifrices were used containing 0.1% NaF, 0.1% NaF and 2% chlorhexidine, and 2% chlorhexidine, respectively. The caries increment and gingival conditions over a period of 2 years were recorded. The caries data of the groups were compared and related to two reference groups in order to estimate a possible influence upon the study results by a change in caries incidence general to the area and age groups in question. There was less caries in the group using the dentifrice containing fluoride and chlorhexidine than in the two other test groups. The differences in caries increment between the groups were not statistically significant. The gingival health seemed to improve in all groups, but there were no statistically significant differences between the groups. The caries data from the reference groups indicated that the general trend towards reduced caries incidence was different from that of the study group." ]	Supported by more than half a century of research, the benefits of fluoride toothpastes are firmly established. Taken together, the trials are of relatively high quality, and provide clear evidence that fluoride toothpastes are efficacious in preventing caries.
CD001869	[ "18439948", "8651631", "17202945", "17414047", "17942873", "10593672" ]	[ "Acyclovir plus steroid vs steroid alone in the treatment of Bell's palsy.", "Bell's palsy treatment with acyclovir and prednisone compared with prednisone alone: a double-blind, randomized, controlled trial.", "Reactivation of herpes simplex virus type 1 and varicella-zoster virus and therapeutic effects of combination therapy with prednisolone and valacyclovir in patients with Bell's palsy.", "Valacyclovir and prednisolone treatment for Bell's palsy: a multicenter, randomized, placebo-controlled study.", "Early treatment with prednisolone or acyclovir in Bell's palsy.", "Corticosteroid treatment of childhood Bell's palsy." ]	[ "The pathogenetic mechanism of Bell's palsy is thought to involve herpes simplex virus reactivation within the geniculate ganglion, followed by inflammation and entrapment of the nerve at the meatal foramen. We therefore compared the therapeutic effect of acyclovir plus steroid vs steroid alone, in combination with physical therapy, in patients with Bell's palsy.\n In a double-blind, randomized, prospective trial, 91 patients were randomized to treatment with acyclovir and prednisone (44 patients) or prednisone alone (47 patients). All patients underwent physical therapy. The follow-up period was greater than 6 months or encompassed the period of complete recovery from paralysis. House-Brackmann grade was evaluated 2 and 6 months after onset, with complete and satisfactory recovery defined as House-Brackmann grades I and II, respectively.\n The overall recovery rate of patients treated with steroid and acyclovir (93.1%) was greater than that of patients treated with steroid alone (85.1%), but the difference was not statistically significant.\n The benefit of acyclovir in Bell's palsy has not been definitively established.", "In a double-blind study, we compared the final outcome of 99 Bell's palsy patients treated with either acyclovir-prednisone (53 patients) or placebo-prednisone (46 patients). For patients receiving acyclovir, the dosage was 2,000 mg (400 mg 5 times daily) for 10 days. Electrical tests included electroneurography and the maximal stimulation test. Univariate comparisons of outcome and electrical tests between the two groups were made with chi 2 analysis, Fisher's exact test, and t-tests. The outcome in acyclovir-prednisone-treated patients was superior to that in placebo-prednisone-treated patients. Treatment with acyclovir-prednisone was statistically more effective in returning volitional muscle motion (recovery profile of 10; p = .02) and in preventing partial nerve degeneration (p = .05) than placebo-prednisone treatment. The t-tests indicated that the recovery profile and index means were significantly better for the acyclovir-treated group (recovery profile t = 1.99, p = .051; recovery index t = 2.10, p = .040). We conclude that acyclovir-prednisone is superior to prednisone alone in treating Bell's palsy patients and suggest that herpes simplex is the probable cause of Bell's palsy.", "To determine whether reactivation of herpes simplex virus (HSV) type 1 or varicella-zoster virus (VZV) is the main cause of Bell's palsy and whether antiviral drugs bring about recovery from Bell's palsy.\n Randomized, multicenter, controlled study.\n One hundred fifty patients with Bell's palsy were enrolled in this study. The patients were randomly assigned to a prednisolone group or a prednisolone-valacyclovir group, in whom virologic examinations for HSV-1 and VZV were performed by simple randomization scheme in sealed envelopes. The recovery rates among various groups were analyzed using the Kaplan-Meier method and the Cox proportional hazards model.\n Reactivation of HSV-1, VZV, and both viruses was detected in 15.3%, 14.7%, and 4.0% of patients, respectively. There was no significant difference in recovery rates between the prednisolone group and the prednisolone-valacyclovir group, although recovery in the patients with HSV-1 reactivation tended to be higher in the prednisolone-valacyclovir group than in the prednisolone group. There was a significant difference in recovery among age groups and between individuals with complete and incomplete paralysis.\n Reactivation of HSV-1 or VZV was observed in 34% of the patients with Bell's palsy. The effect of combination therapy with prednisolone and valacyclovir on recovery was not significantly higher than that with prednisolone alone.", "To investigate the effects of valacyclovir and prednisolone in comparison with those of placebo and prednisolone for the treatment of Bell's palsy, excluding zoster sine herpete.\n Prospective, multicenter, randomized placebo-controlled study.\n Six academic tertiary referral centers.\n Ultimately, 221 patients with Bell's palsy who were treated within 7 days of the onset. Serological and polymerase chain reaction examinations were performed to distinguish Bell's palsy from zoster sine herpete.\n The patients were treated with either valacyclovir (dosage, 1,000 mg/d for 5 days) plus prednisolone (VP [n = 114]) or placebo plus prednisolone (PP [n = 107]) administered orally.\n Recovery from the palsy was defined as a score higher than 36 using Yanagihara 40-point scoring system without facial contracture or synkinesis. The patients were followed up until complete recovery occurred or for more than 6 months in cases with a poor prognosis.\n The overall rate of patient recovery among those treated with VP (96.5%) was significantly better (p < 0.05) than the rate among those treated with PP (89.7%). The rate of patient recovery was also analyzed by classifying the initial severity of facial palsy. In cases of complete or severe palsy, the rates of patients treated with VP and PP who recovered were 95.7% (n = 92) and 86.6% (n = 82), respectively; the recovery rate for treatment with VP was significantly better than that with PP (p < 0.05).\n The valacyclovir and prednisolone therapy was more effective in treating Bell's palsy, excluding zoster sine herpete, than the conventional prednisolone therapy. To our knowledge, this is the first controlled study of an antiviral agent in the treatment of a sufficient number of Bell's palsy cases based on an etiologic background.", "Corticosteroids and antiviral agents are widely used to treat the early stages of idiopathic facial paralysis (i.e., Bell's palsy), but their effectiveness is uncertain.\n We conducted a double-blind, placebo-controlled, randomized, factorial trial involving patients with Bell's palsy who were recruited within 72 hours after the onset of symptoms. Patients were randomly assigned to receive 10 days of treatment with prednisolone, acyclovir, both agents, or placebo. The primary outcome was recovery of facial function, as rated on the House-Brackmann scale. Secondary outcomes included quality of life, appearance, and pain.\n Final outcomes were assessed for 496 of 551 patients who underwent randomization. At 3 months, the proportions of patients who had recovered facial function were 83.0% in the prednisolone group as compared with 63.6% among patients who did not receive prednisolone (P<0.001) and 71.2% in the acyclovir group as compared with 75.7% among patients who did not receive acyclovir (adjusted P=0.50). After 9 months, these proportions were 94.4% for prednisolone and 81.6% for no prednisolone (P<0.001) and 85.4% for acyclovir and 90.8% for no acyclovir (adjusted P=0.10). For patients treated with both drugs, the proportions were 79.7% at 3 months (P<0.001) and 92.7% at 9 months (P<0.001). There were no clinically significant differences between the treatment groups in secondary outcomes. There were no serious adverse events in any group.\n In patients with Bell's palsy, early treatment with prednisolone significantly improves the chances of complete recovery at 3 and 9 months. There is no evidence of a benefit of acyclovir given alone or an additional benefit of acyclovir in combination with prednisolone. (Current Controlled Trials number, ISRCTN71548196 [controlled-trials.com].).\n Copyright 2007 Massachusetts Medical Society.", "The therapeutic effect of corticosteroids in acute idiopathic peripheral nerve paralysis (Bell's palsy) in children is controversial. The authors evaluated the effect of steroids on the early and late outcome of children with Bell's palsy in a prospective randomized controlled setting. Forty-two patients (21 females, 21 males) with complete paralysis were enrolled in the study. Group 1 (n = 21) received methylprednisolone (1 mg/kg daily for 10 days orally); Group 2 (n = 21) did not. All patients were observed in the first 3 days of the disease and at 4, 6, and 12 months of follow-up. The mean age of Group 1 was 52.4 +/- 4.3 months, not significantly different from that of Group 2. In Group 1, 86% and 100% exhibited normal nerve function at 4 and 6 months of follow-up, respectively; in Group 2, 72% and 86% demonstrated complete recovery at 4 and 6 months, respectively, with improvement in all patients by 12 months. The improvement rates between the treated and untreated groups did not differ significantly. No side effects necessitated steroid withdrawal. The results of this study indicate that steroid therapy initiated at an early stage of childhood Bell's palsy does not significantly improve the outcome." ]	High quality evidence showed no significant benefit from anti-herpes simplex antivirals compared with placebo in producing complete recovery from Bell's palsy. Moderate quality evidence showed that antivirals were significantly less likely than corticosteroids to produce complete recovery.
CD005983	[ "17200252" ]	[ "A randomized, controlled trial of heparin versus placebo infusion to prolong the usability of peripherally placed percutaneous central venous catheters (PCVCs) in neonates: the HIP (Heparin Infusion for PCVC) study." ]	[ "Mechanical and infectious complications shorten the effective duration of peripherally inserted central venous catheters. Heparin use to prevent such complications and prolong the usability of peripherally inserted central venous catheters is inconclusive.\n Our goal was to evaluate the effectiveness of heparin in prolonging the usability of peripherally inserted central venous catheters in neonates.\n We performed a multicenter, randomized, controlled trial of heparin infusion (0.5 U/kg per hour) versus placebo for peripherally inserted central venous catheters in neonates. The primary outcome was duration of catheter use. Secondary outcomes were occlusion, catheter-related sepsis, thrombosis, and adverse effects of heparin. To detect a 168-hour (1-week) difference in the duration of catheter use, 192 patients were needed. Kaplan-Meier and Cox regression analyses were performed.\n A total of 201 neonates were enrolled (heparin group: n = 100; control group: n = 101). Baseline demographics were similar between the groups. Duration of catheter use was longer in the infants in the heparin versus the placebo group. Study center, gender, birth weight, and type and position of the catheter were not predictors of duration of catheter use. For those in the heparin versus the placebo group, the incidence of elective catheter removal (therapy completed) was 63% vs 42%, of occlusion was 6% vs 31%, of thrombosis was 20% vs 21%, and of catheter-related sepsis was 10% vs 6%, respectively. No adverse events were noted.\n Heparin infusion prolonged the duration of peripherally inserted central venous catheter usability, which permitted a higher percentage of neonates to complete therapy without increasing adverse effects." ]	Two eligible studies on the use of heparin-bonded catheters versus placebo in children were identified. The use of heparin-bonded catheters is a promising therapy but warrants further studies.
CD007913	[ "15235901", "1381626", "10735900", "8695241", "7492381", "16148021", "8605328", "7532056" ]	[ "A prospective randomised evaluation of G-CSF or G-CSF plus oral antibiotics in chemotherapy-treated patients at high risk of developing febrile neutropenia.", "Granulocyte colony-stimulating factor to prevent dose-limiting neutropenia in non-Hodgkin's lymphoma: a randomized controlled trial.", "Use of recombinant human granulocyte colony-stimulating factor to increase chemotherapy dose-intensity: a randomized trial in very high-risk childhood acute lymphoblastic leukemia.", "A randomised study comparing granulocyte-colony stimulating factor (G-CSF) with G-CSF plus thymostimulin in the treatment of haematological toxicity in patients with advanced breast cancer after high dose mitoxantrone therapy.", "Effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on hematologic toxicity induced by high-dose chemotherapy in patients with metastatic breast cancer.", "Postoperative dose-dense sequential chemotherapy with epirubicin, followed by CMF with or without paclitaxel, in patients with high-risk operable breast cancer: a randomized phase III study conducted by the Hellenic Cooperative Oncology Group.", "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.", "Effect of granulocyte colony-stimulating factor in patients with diffuse large cell lymphoma treated with intensive chemotherapy." ]	[ "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.", "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.", "To determine whether the use of a recombinant human granulocyte colony-stimulating factor ([G-CSF] lenogastrim) can increase the chemotherapy dose-intensity (CDI) delivered during consolidation chemotherapy of childhood acute lymphoblastic leukemia (ALL).\n Sixty-seven children with very high-risk ALL were randomized (slow early response to therapy, 55 patients; translocation t(9;22) or t(4;11), 12 patients). Consolidation consisted of six courses of chemotherapy; the first, third, and fifth courses were a combination of high-dose cytarabine, etoposide, and dexamethasone (R3), whereas the second, fourth, and sixth courses included vincristine, prednisone, cyclophosphamide, doxorubicin, and methotrexate (COPADM). G-CSF was given after each course, and the next scheduled course was started as soon as neutrophil count was > 1 x 10(9)/L and platelet count was > 100 x 10(9)/L. CDI was calculated using the interval from day 1 of the first course to hematologic recovery after the fifth course (100% CDI = 105-day interval).\n CDI was significantly increased in the G-CSF group compared with the non-G-CSF group (mean +/- 95% confidence interval, 105 +/- 5% v 91 +/- 4%; P <.001). This higher intensity was a result of shorter post-R3 intervals in the G-CSF group, whereas the post-COPADM intervals were not statistically reduced. After the R3 courses, the number of days with fever and intravenous antibiotics and duration of hospitalization were significantly decreased by G-CSF, whereas reductions observed after COPADM were not statistically significant. Duration of granulocytopenia was reduced in the G-CSF group, but thrombocytopenia was prolonged, and the number of platelet transfusions was increased. Finally, the 3-year probability of event-free survival was not different between the two groups.\n G-CSF can increase CDI in high-risk childhood ALL. Its effects depend on the chemotherapy regimen given before G-CSF administration. In our study, a higher CDI did not improve disease control.", "54 patients with advanced breast cancer were randomised into a prospective, non-blinded, controlled trial to receive: mitoxantrone 28 mg/m2 intravenous day 1 and granulocyte-colony stimulating factor (G-CSF) 5 micrograms/kg/day subcutaneously days 2 to 16 (n = 27) or the same regimen plus thymostimulin (TS) 50 mg/day intramuscular at days 2 to 16 (n = 27). The median time to reach a neutrophil count greater than 0.5 x 10(9)/l was lower in the G-CSF+TS treated group (9.13 versus 3.24 days; P < 0.0005). More patients experienced neutropenic fever in the G-CSF group than in the G-CSF+TS group (59.3% versus 22.2%, P = 0.0119). The incidence, duration and severity of clinically or bacteriologically documented infection were lower in patients who received TS. 16 patients (59.3%) in the G-CSF group contracted infection, and 4 patients (14.8%) receiving G-CSF+TS (P = 0.0016). These data indicate that the combination of G-CSF and TS is well-tolerated and may enhance haematological recovery following myelosuppressive chemotherapy in patients with advanced breast cancer.", "Twenty patients with recurrent metastatic breast cancer treated with high-dose myelosuppressive antineoplastic drugs (cyclophosphamide 2.5 g/m2 or epirubicin 130 mg/m2, both every 3 weeks) as first or second line chemotherapy were randomized in a prospective study to GM-CSF 5 micrograms/kg per day (n = 11) or control (n = 9). Significant reduction in granulocyte nadir duration (2 days with GM-CSF vs. 7 days) and severity (0.4 x 10(9)/l with GM-CSF vs. 0.2 x 10(9)/l) was found. No difference in frequency of neutropenic fever or antibiotic use could be observed. Even though the patients treated with GM-CSF at random were more heavily pretreated with chemotherapy, there was a surprisingly higher response rate in these patients as compared to the control-arm, namely 64% vs. 28.5%. However, this difference was not statistically significant. No severe side-effects were seen, but presumably due to GM-CSF one patient developed an allergic type 1 reaction and one patient a possible pericardial exudation. Both were fully reversible after cessation of the cytokine treatment.", "The aim of this study was to explore the effect of dose-dense sequential chemotherapy with or without paclitaxel primarily on disease-free survival (DFS) and secondarily on overall survival (OS) in patients with high-risk operable breast cancer.\n From June 1997 until November 2000, 604 patients with T1-3N1M0 or T3N0M0 tumors were randomized to three cycles of epirubicin 110 mg/m2 followed by three cycles of paclitaxel 250 mg/m2 followed by three cycles of 'intensified' CMF (cyclophosphamide 840 mg/m2, methotrexate 47 mg/m2 and fluorouracil 840 mg/m2) (group A), or to four cycles of epirubicin followed by four cycles of CMF, as in group A (group B). All cycles were given every 2 weeks with granulocyte colony-stimulating factor support.\n A total of 595 patients were eligible. Median follow-up was 61.7 months for group A and 62 months for group B. The 3-year DFS was 80% in group A and 77% in group B. Survival rates were 93% and 90%, respectively. The effect of treatment on the hazard of death was different according to hormonal receptor status. More specifically, in patients with negative receptor status the hazard of death was significantly higher for group B (hazard ratio 2.42). Both regimens were well tolerated and severe acute side-effects were infrequent. No cases of severe cardiotoxicity or acute leukemia were recorded.\n The present study failed to demonstrate a significant difference in DFS or OS between the two treatment groups. However, our study has shown clearly that high-dose paclitaxel can be safely incorporated to dose-dense sequential chemotherapy.", "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.", "We investigated whether Granulocyte colony-stimulating factor (G-CSF) could prevent myelotoxicity or accelerate hematopoietic recovery after intensive chemotherapy in previously untreated patients with diffuse large cell lymphoma (DLCL). Forty-two patients were included in a prospective clinical trial in which alternating chemotherapy ESAP (etoposide, Solu-Medrol, cytosine arabinoside, cis-platinum), m-BECOD (low doses methotrexate, bleomycin, epirubicin, cyclophosphamide, vincristine, dexamethasone), MVPP-Bleo (mitoxantrone, vincristine, prednisone, procarbazine, bleomycin) were administered by 9 cycles. Each cycle was followed by 10 days of G-CSF (5 micrograms/kg/day) started five days after chemotherapy compared to a control group which received chemotherapy without G-CSF support. Leucocytes and granulocytes were significantly higher in patients receiving G-CSF compared to the control group. The total number of days of leukopenia (WBC counts below 2.0 x 10(9)/L and absolute granulocytes below 1.0 x 10(9)/L) were longer in the patients without G-CSF compared to those who received G-CSF (14.1 days versus 1.9 days). Delays in treatment were most frequent in the control group: 38% versus 4% in all cycles. Infection episodes occurred in 41 out of 168 cycles (25%) in the control group compared to 7 out of 172 (4%) in the G-CSF arm. Complete response was achieved in 12 out of 22 (54%) in the control group compared to 16 out 20 (80%) in the patients who received G-CSF. Toxicity secondary to G-CSF was mild. G-CSF can be administered safely to patients with DLCL and results in improved hematologic recovery after intensive chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)" ]	In patients with breast cancer receiving chemotherapy, CSFs have shown evidence of beneﬁt in the prevention of FN. There is evidence, though less reliable, of a decrease of all-cause mortality during chemotherapy and a reduced need for hospital care. No reliable evidence was found for a reduction of infection-related mortality, a higher dose intensity of chemotherapy with CSFs or diminished rates of severe neutropenia and infections. The majority of adverse events reported from CSF use were bone pain and injection-site reactions but no conclusions could be drawn regarding late-term side effects.
CD003534	[ "10325895", "10678614", "12532097", "12765916", "11555383", "8959118", "16882819", "14512127", "11559968", "8222787", "10936116", "11101186", "1412112", "2665584", "9828851", "10856150", "9949318", "14745658", "17629923", "8511727", "10492263", "7664857", "10491451", "10926345", "8958890", "11477728", "8887604", "10974132", "11101185", "1955002", "10936117", "14694242", "18475734", "9517598", "10329812" ]	[ "Addition of salmeterol versus doubling the dose of fluticasone propionate in patients with mild to moderate asthma.", "Low- and high-dose fluticasone propionate in asthma; effects during and after treatment.", "Steroid-sparing effects of fluticasone propionate 100 microg and salmeterol 50 microg administered twice daily in a single product in patients previously controlled with fluticasone propionate 250 microg administered twice daily.", "Fluticasone propionate in asthma: a long term dose comparison study.", "Improved safety with equivalent asthma control in adults with chronic severe asthma on high-dose fluticasone propionate.", "Fluticasone propionate 1 mg daily and beclomethasone dipropionate 2 mg daily: a comparison over 1 yr.", "High-dose inhaled fluticasone does not replace oral prednisolone in children with mild to moderate acute asthma.", "A randomized, double-blind, double-dummy, parallel-group, multicenter, dose-reduction trial of the minimal effective doses of budesonide and fluticasone dry-powder inhalers in adults with mild to moderate asthma.", "A comparison of clinical use of fluticasone propionate and beclomethasone dipropionate in pediatric asthma.", "A dose-ranging study of fluticasone propionate in adult patients with moderate asthma. International Study Group.", "A dose-ranging study of fluticasone propionate administered once daily via multidose powder inhaler to patients with moderate asthma.", "Efficacy and safety of dry powder fluticasone propionate in children with persistent asthma.", "Corticosteroids in acute severe asthma: effectiveness of low doses.", "High doses of inhaled corticosteroids in unstable chronic asthma. A multicenter, double-blind, placebo-controlled study.", "Fluticasone propionate 750 micrograms/day versus beclomethasone dipropionate 1500 micrograms/day: comparison of efficacy and adrenal function in paediatric asthma.", "Comparison of once- and twice-daily dosing of fluticasone propionate 200 micrograms per day administered by diskus device in patients with asthma treated with or without inhaled corticosteroids.", "Fluticasone propionate powder: oral corticosteroid-sparing effect and improved lung function and quality of life in patients with severe chronic asthma.", "Salmeterol/fluticasone propionate (50/250 microg) combination is superior to double dose fluticasone (500 microg) for the treatment of symptomatic moderate asthma.", "Comparison of the effects of salmeterol/fluticasone propionate with fluticasone propionate on airway physiology in adults with mild persistent asthma.", "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.", "Fluticasone alone or in combination with salmeterol vs triamcinolone in asthma.", "High dose fluticasone propionate, 1 mg daily, versus fluticasone propionate, 2 mg daily, or budesonide, 1.6 mg daily, in patients with chronic severe asthma. International Study Group.", "Effects of inhaled fluticasone and oral prednisolone on clinical and inflammatory parameters in patients with asthma.", "Salmeterol/fluticasone propionate combination therapy 50/250 microg twice daily is more effective than budesonide 800 microg twice daily in treating moderate to severe asthma.", "Comparison of short courses of oral prednisolone and fluticasone propionate in the treatment of adults with acute exacerbations of asthma in primary care.", "Effects of single-dose fluticasone on exercise-induced asthma in asthmatic children: a pilot study.", "Fluticasone propionate in children with moderate asthma.", "A comparison of inhaled fluticasone and oral prednisone for children with severe acute asthma.", "Fluticasone propionate versus zafirlukast: effect in patients previously receiving inhaled corticosteroid therapy.", "High-dose beclomethasone: oral steroid-sparing effect in severe asthmatic patients.", "Long-term efficacy and safety of fluticasone propionate powder administered once or twice daily via inhaler to patients with moderate asthma.", "Time course of action of two inhaled corticosteroids, fluticasone propionate and budesonide.", "A blinded comparison of fluticasone propionate with budesonide via powder devices in adult patients with moderate-to-severe asthma: a clinical evaluation.", "Safety and efficacy of fluticasone and beclomethasone in moderate to severe asthma. Belgian Multicenter Study Group.", "A comparison of multiple doses of fluticasone propionate and beclomethasone dipropionate in subjects with persistent asthma." ]	[ "The objective of this multicentre, randomised, double blind, parallel group study was to compare the efficacy and safety of the addition of salmeterol with that of doubling the dose of fluticasone propionate in asthmatic patients not controlled by a low or intermediate dose of inhaled corticosteroids.\n After a four week run in period of treatment with fluticasone propionate (100 micrograms twice daily if pre-trial dose was 400-600 micrograms inhaled corticosteroids or 250 micrograms twice daily if pre-trial dose was 800-1200 micrograms inhaled corticosteroids), 274 patients were randomised to treatment for 12 weeks with either salmeterol 50 micrograms twice daily plus the run in dose of fluticasone propionate or twice the run in dose of fluticasone propionate (200 or 500 micrograms twice daily). Outcome measures were daily records of peak expiratory flow (PEF), symptom scores, and clinic lung function.\n The improvements in both the morning and evening PEF were better in the salmeterol than in the fluticasone propionate group, the mean increase in morning PEF being 19 l/min higher (95% CI 11.0 to 26.1) and in evening PEF being 16 l/min (95% CI 18.4 to 24.0) higher in the salmeterol group. The increase in forced expiratory volume in one second (FEV1) was 0.09 1 greater in the salmeterol group than in the fluticasone propionate group after four weeks of treatment (95% CI 0.01 to 0.18), but not after 12 weeks. Both regimens showed an increase in symptom free days and a reduction in the need for rescue salbutamol both during the day and the night, but these improvements were greater in the salmeterol group. There were no significant differences between the groups in adverse effects or in the number of rescue course of oral corticosteroids.\n In this group of patients still symptomatic despite 100 or 250 micrograms fluticasone propionate twice daily, the addition of salmetterol caused a greater improvement in lung function and symptom control than doubling the dose of fluticasone propionate.", "The dose dependency of the effects of inhaled corticosteroids on markers of asthmatic airway inflammation have not been well studied. There is a need to study the dose/response effects on this inflammation. In order to determine the dose/response effects of fluticasone propionate (FP), 24 asthmatic subjects were randomized to low- (100 microg x day(-1)) or high-dose (1,000 microg x day(-1)) FP for six weeks followed by placebo for 3 weeks. During treatment, the median increase in forced expiratory volume in one second (FEV1)was 12% in the high-dose group (p<0.05) and 10% in the low-dose group (p<0.05) (p>0.05 between groups); the median decrease in the percentage of sputum eosinophils was 93% in the high-dose group (p<0.05) and 46% in the low-dose group (p<0.05) (p>0.05 between groups). Symptoms, salbutamol use, morning peak flow, provocative concentration of methacholine causing a 20% fall in FEV1 (PC20), sputum eosinophil cationic protein concentration and tryptase activity improved significantly in both groups (p<0.05), but only the improvement in salbutamol use was greater in the high-dose group (p<0.05). During the run-out, the improvements in FEV1 and PC20 were rapidly reversed in both groups, but the improvements in peak flow and tryptase activity persisted; the improvement in sputum eosinophil concentration persisted only in the high-dose group (p<0.05). It was concluded that dose/response effects for FP are not easily demonstrable because low-dose FP is quite effective. For most outcomes, the effects of high- and low-dose FP are relatively short-lived after treatment is stopped. This finding raises questions about the extent to which inhaled corticosteroids are disease-modifying in asthma.", "Concurrent use of an inhaled corticosteroid (ICS) and an inhaled long-acting beta2-agonist provides better overall asthma control than the use of higher doses of ICS alone.\n The purpose of this investigation was to determine whether fluticasone propionate (FP) combined with salmeterol in the Diskus device can be used to reduce the dose of ICS in patients currently stable on medium-dose ICS while maintaining asthma control.\n This was a randomized, double-blind, parallel-group, 12- to 24-week trial consisting of a 3-part run-in period. The run-in period was designed to first establish FP 250 microg administered twice a day (bid) via Diskus as the minimum effective dose. During run-in period 1, patients received FP 220 microg bid or the equivalent for 10 to 14 days. Controlled patients moved to run-in period 2 (5-28 days), which assessed asthma stability on FP 100 microg bid administered via Diskus. Only patients who became unstable on FP 100 microg bid were eligible to enter run-in period 3 (26-30 days), during which they were placed on FP 250 microg bid and those regaining asthma control were eligible for randomization. The primary efficacy endpoint was the proportion of patients who remained in the study with no evidence of worsening asthma. Secondary efficacy measures included FEV1, morning peak expiratory flow, percent of symptom-free days, and daily albuterol use.\n Only 5% of patients treated with FP100/salmeterol withdrew because of worsening asthma in the first 12 weeks; this compared with 7% in the FP250 group. All patients from a subset of sites continued in the study for an additional 12 weeks; only an additional 1% of patients treated with either FP100/salmeterol or FP250 withdrew because of worsening asthma. Secondary efficacy measures confirmed primary efficacy results.\n In patients requiring FP250 bid for asthma stability, FP100/salmeterol bid was steroid-sparing, allowing a 60% reduction in the FP dose while maintaining overall asthma control.", "Few dose ranging studies have investigated optimal dosing with inhaled corticosteroids in children with asthma.\n To compare the efficacy and tolerability of fluticasone propionate 100 or 200 microg twice daily in children with moderate to severe asthma for one year.\n One year, randomised, double blind, parallel group, multicentre study. Children aged 4-11 years (n = 528) with moderate to severe asthma who had previously received high dose inhaled corticosteroids were given fluticasone propionate 100 or 200 microg twice daily for the 52 week treatment period. Efficacy (exacerbations, lung function, and symptoms) and tolerability (adverse events and cortisol levels) were measured.\n There was a non-significant decreased risk of experiencing an exacerbation at any time with fluticasone propionate 200 microg twice daily compared with fluticasone propionate 100 microg twice daily. This difference reached significance among patients with more severe asthma (defined by previous inhaled corticosteroid dose >800 microg/day). Daily record card morning peak expiratory flow (PEF) in the total population improved significantly more with the higher dose of fluticasone propionate (between group difference, weeks 1-52: 11.4 l/min). Clinic visit mean PEF improved from baseline with both doses, but the response was significantly greater with the higher dose (between group difference, week 52: 17.8 l/min). Both doses were equally well tolerated and overnight urinary cortisol concentrations were unchanged or slightly increased during treatment with either dose.\n This long term dose comparison study shows that treatment with fluticasone propionate 200 micro g twice daily may offer benefits over a lower dose, particularly in children with more severe asthma.", "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.", "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.", "Inhaled corticosteroids are not as effective as oral corticosteroids in school-aged children with severe acute asthma. It is uncertain how inhaled corticosteroids compare with oral corticosteroids in mild to moderate exacerbations.\n The purpose of this work was to determine whether there is a significant difference in the percentage of predicted forced expiratory volume in 1 second in children with mild to moderate acute asthma treated with either inhaled fluticasone or oral prednisolone.\n This was a randomized, double-blind controlled trial conducted between 2001 and 2004 in a tertiary care pediatric emergency department. We studied a convenience sample of 69 previously healthy children 5 to 17 years of age with acute asthma and forced expiratory volume in 1 second at 50% to 79% predicted value; 41 families refused participation. Albuterol was given in the emergency department and salmeterol was given after discharge to all patients, as well as either 2 mg of fluticasone via metered dose inhaler and valved holding chamber in the emergency department plus 500 microg twice daily via Diskus for 10 doses after discharge (fluticasone group, N = 35) or 2 mg/kg of oral prednisolone in the emergency department plus 5 daily doses of 1 mg/kg of prednisolone after discharge (prednisolone group, N = 34). We measured a priori defined absolute change in percent predicted forced expiratory volume in 1 second from baseline to 4 and 48 hours in the 2 groups. RESULTS. At 240 minutes, the forced expiratory volume in 1 second increased by 19.1% +/- 12.7% in the fluticasone group and 29.8% +/- 15.5% in the prednisolone group. At 48 hours, this difference was no longer significant (estimated difference: 4.0 +/- 3.4; P = .14). The relapse rates by 48 hours were 12.5% and 0% in the fluticasone group and prednisolone group, respectively.\n Airway obstruction in children with mild to moderate acute asthma in the emergency department improves faster on oral than inhaled corticosteroids.", "Inhaled corticosteroids are established first-line anti-inflammatory treatment for asthma. Clinical trials comparing inhaled corticosteroids must take into consideration that because of their excellent effect at low doses, they typically induce a near-maximal response in asthma patients.\n The aim of the present dose-response study was to estimate the minimal effective doses (MEDs) of budesonide and of fluticasone propionate via dry-powder inhaler in adults with mild to moderate asthma.\n This was a randomized, double-blind, double-dummy, parallel-group, multicenter, dose-reduction trial performed in adults to compare these 2 inhaled corticosteroids. After a 4- to 6-week run-in period with beclomethasone dipropionate 2000 pg/d, patients fulfilling defined criteria for asthma control were randomly allocated to treatment with budesonide or fluticasone, both administered BID at a total of 800 pg/d. At 5-week intervals, the dose was reduced to 400 and then 200 pg/d (200 and 100 pg BID) if asthma control was maintained according to further defined criteria. The MED was defined as the last dose level before deterioration of asthma control.\n Subjects were 197 asthmatic patients with a mean age of 40.6 years in the budesonide group and 41.5 years in the fluticasone group. In both groups, baseline mean forced expiratory volume in 1 second (FEV(1)) was 79.4% of the predicted normal volume and baseline mean FEV(1) reversibility was 22.3%. The median MED for both groups was 400 microg/d, with no detectable difference in dis-tributions. The budesonide-to-fluticasone ratio for the geometric mean MED was 123% (95% CI, 99-153 [not significant]). No statistically significant differences regarding lung function, symptom scores, or rescue medication usage were found between the treatment groups during the first treatment period. Adverse-event profiles were similar in both groups, and no unexpected adverse events were considered to be caused by the study drugs.\n This effect-controlled study did not detect a statistically significant difference between the MEDs for budesonide and fluticasone via dry-powder inhaler in adults with mild to moderate asthma.", "Inhaled steroids play a very important role in the prevention and treatment of asthma. Previous studies indicated that fluticasone propionate (FP) had low bioavailability and high local potency. However, the laboratory data in these studies were not obtained among Taiwan population. It is very important that native data should be established. Thus a 12-week research program was designed, involving 77 patients, 51 for FP group and 26 for beclomethasone dipropionate (BD) group. The objects were victims of moderate to severe asthma and their age ranged from 4 to 14 years old. An open, comparative and randomized method was adopted. Except for the 4-week-later daytime symptom score(P = 0.033, BD group was better), no other significant differences were found between the two groups in the symptom score improvement(P > 0.05). All the P-values for the daytime & night-time scores were lower than 0.001, which means obvious improvement after treatment in both groups. P-value for PEF improvement was 0.003 after 4 weeks (BD group was better) and 0.943 after 8 weeks; for FEV1 improvement, it was 0.005 after 4 weeks(BD group was better) and 0.252 after 8 weeks; and for FEV1/FVC improvements, it was 0.067 after 4 weeks and 0.097 after 8 weeks. There was no statistic significance in total eosinophil count (TEC), IgE, eosinophil cationic protein (ECP) serum level changes after 4 or 8 weeks. Adverse effects were all anticipated and no statistic significance showed up, either, between the two groups or in the cortisol levels (P > 0.05). In conclusion, native data indicated that the potency of 100 micrograms of FP was equal to that of 200 micrograms of BD and that few side effects were noted in FP group. It is recommended that this drug be introduced for clinical use.", "In this 4-week, multicenter, double-blind, randomized, parallel group study, the dose-effect relationship of four doses of inhaled fluticasone propionate (50, 100, 200, and 400 micrograms twice daily) was investigated and compared with beclomethasone dipropionate, 200 micrograms twice daily. A total of 672 patients with moderate asthma currently receiving 1,000 micrograms/d or less of an inhaled steroid were recruited. The study demonstrated a significant dose-related improvement in lung function with fluticasone propionate. Linear dose-related increases were observed in morning (increase per doubling dose was 4.3 L/min; 95 percent confidence interval [CI], 1.8, 6.8 L/min; p = 0.001) and evening peak expiratory flow rate (PEFR) (increase per doubling dose was 3.0 L/min; 95 percent CI, 0.5, 5.5 L/min; p = 0.017), clinic lung function (at 4 weeks, increase in percent predicted PEFR per doubling dose = 1.1 percent; 95 percent CI, 0.2, 2.1 percent; p = 0.022; increase in percent predicted FEV1 per doubling dose = 1.1 percent; 95 percent CI, 0.3, 1.9 percent; p = 0.10:increase in percent predicted FVC per doubling dose = 1.3 percent, 95 percent CI, 0.5, 2.1 percent; p = 0.001), and the percentage of symptom-free days over days 1 to 14 of treatment (increase per doubling dose = 1.9, 95 percent CI, 0.0, 3.9; p = 0.048). There was also a dose-related reduction in extra bronchodilator usage (days 1 to 14 p = 0.002; days 15 to 28 p = 0.01). In addition, there was a significant decrease in diurnal variation with increasing doses of fluticasone propionate (decrease per doubling dose = 2.0 L/min, 95 percent CI, 0.4; p = 0.024). The number of asthma exacerbations was also reduced as the dose of fluticasone propionate increased. Fluticasone propionate was well tolerated, adverse events were few, and there was a similar incidence in all groups. Furthermore, there was no evidence of any hypothalamic pituitary adrenal axis suppression. The data from the study were consistent with other clinical studies that have shown fluticasone propionate to be more potent than beclomethasone dipropionate in terms of improvement in lung function. In conclusion, this study provided evidence of a dose-related improvement in asthma control for fluticasone propionate in the dose range 100 to 800 micrograms daily, in patients with moderate asthma.", "This dose-ranging study evaluated the clinical efficacy and safety of inhaled fluticasone propionate administered once daily via a multidose powder inhaler in patients with moderate asthma (FEV(1), 45 to 75% predicted).\n In this multicenter trial, 330 patients (> or = 12 years old) previously receiving inhaled corticosteroids or beta(2)-agonists alone were randomized in a double-blind manner to receive fluticasone propionate at 100, 200, or 500 microg once daily or matching placebo for 12 weeks.\n Once-daily treatment with fluticasone propionate resulted in an improvement in efficacy variables, such as FEV(1), morning and evening peak expiratory flow (PEF), asthma symptom scores, nighttime awakenings, albuterol use, and duration of study participation. A dose-related trend was observed for improvements in morning and evening PEF and albuterol use. Statistical significance for pairwise comparisons was achieved for 200 microg and 500 microg fluticasone propionate vs placebo for all efficacy variables, and for 100 microg fluticasone propionate vs placebo for morning and evening PEF at most or all time points. Drug-related adverse events were few (< or = 5%) and mostly related to the topical effects of inhaled corticosteroids. No dose-response effect or clinically relevant differences were observed in morning plasma cortisol concentrations or after cosyntropin stimulation.\n Once-daily treatment with fluticasone propionate was well tolerated and demonstrated some dose-related trends in improvements in lung function and asthma control in patients with moderate asthma.", "Flovent Diskus is a powder formulation of the inhaled corticosteroid fluticasone propionate (FP) delivered via a breath-actuated, multidose inhaler.\n To determine the efficacy and safety of dry powder FP administered once or twice daily (200 microg per day) to children with persistent asthma.\n Twelve-week, randomized, double-blind, placebo-controlled, multicenter trial with a 52-week, open-label extension. Children aged 4 to 11 were required to have pulmonary function 50% to 85% of predicted values. The population was stratified for baseline therapy (inhaled corticosteroid/cromolyn or bronchodilators only). After a 2-week placebo run-in, 242 patients received dry powder FP 200 microg each morning, dry powder FP 100 microg BID, or placebo for 12 weeks; 192 were rerandomized to the QD or BID regimen for an additional 52 weeks of open-label treatment. Primary endpoints were mean changes in FEV1 and morning PEF recorded at clinic visits.\n Both dry powder FP regimens significantly improved FEV1, evening PEF, and asthma symptoms at the double-blind phase endpoint (P < or = .017 compared with placebo). The BID regimen also significantly improved morning PEF and nighttime awakenings due to asthma (P < or = .005). Among patients previously treated with inhaled corticosteroids/cromolyn, improvements observed with the QD and BID regimens were similar. Patients switched from BID to open-label QD treatment showed additional improvements at week 52 generally comparable to patients who received the BID regimen during both phases. Fluticasone propionate was well tolerated for up to 64 weeks with few reports of drug-related adverse events or morning plasma cortisol abnormalities.\n Once daily dosing of dry powder FP 200 microg is an effective and convenient alternative for children whose asthma is controlled with a more frequent dosing regimen of inhaled corticosteroids.", "Although the need for corticosteroids in acute severe asthma is well established the appropriate dose is not known.\n The response to intravenous hydrocortisone 50 mg (low dose), 100 mg (medium dose), and 500 mg (high dose), administered every six hours for 48 hours and followed by oral prednisone, was compared in patients with acute asthma in a double blind randomised study. After initial emergency treatment with bronchodilators subjects received oral theophylline or intravenous aminophylline and nebulised salbutamol four hourly. Patients were given low, medium, or high doses of intravenous hydrocortisone and then 20, 40, or 60 mg/day respectively of oral prednisone with a reducing regimen over the following 12 days. Beclomethasone dipropionate, 400 micrograms twice daily by metered dose inhaler, was also started. Peak expiratory flow (PEF), forced expiratory volume in one second (FEV1), and visual analogue dyspnoea scores (VAS) were recorded daily in hospital and PEF and VAS twice daily after discharge for a total of 12 days.\n The 66 subjects (40 female) who completed the study had a mean (SD) age of 31(14) years. On presentation mean (SD) FEV1% predicted in the low (n = 22), medium (n = 20), and high dose (n = 24) groups was 17(13), 19(12), and 19(11) and after emergency bronchodilator treatment 32(20), 30(12), and 36(13). After 24 hours of treatment the respective post-bronchodilator FEV1% predicted values were 62(22), 62(23), and 65(28) compared with 71(24), 69(22), and 71(24) after 48 hours. No significant difference between the groups was detected. PEF and VAS improved with treatment over the 12 days but was not influenced by steroid dose.\n Hydrocortisone 50 mg intravenously four times a day for two days followed by low dose oral prednisone is as effective in resolving acute severe asthma as 200 or 500 mg of hydrocortisone followed by higher doses of prednisone.", "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.", "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.", "There are limited published data regarding the efficacy of once- versus twice-daily administration of flutica-sone propionate.\n Our purpose was to evaluate the effectiveness of fluticasone propionate powder 200 microg/d administered as a once- or twice-daily dosage regimen in patients who were currently being treated with bronchodilators only (BD patients) and in patients who required inhaled corticosteroids for maintenance treatment of asthma (ICS patients).\n Five hundred seventy patients were randomly assigned to receive one of the following inhaled treatments through the Diskus device (Glaxo Wellcome, Research Triangle Park, NC) for 12 weeks: fluticasone propionate 100 microg twice daily (FP100BID) or 200 microg once daily (FP200QD) or placebo.\n BD patients treated with FP100BID, FP200QD, and placebo had mean increases in FEV(1) from baseline to end point of 0. 49 L, 0.37 L, and 0.21 L, respectively (P <.001, FP100BID vs placebo; P =.05, FP200QD vs placebo). ICS patients treated with FP100BID and FP200QD had mean increases in FEV(1) of 0.27 L and 0.11 L, respectively, compared with a decrease in FEV(1) of -0.08 L with placebo (P <.001, FP100BID vs placebo; P =.023, FP200QD vs placebo). BD patients treated with FP100BID and FP200QD had mean increases in morning peak expiratory flow from baseline to end point of 31 L/min and 27 L/min, respectively, compared with a 1 L/min increase in patients treated with placebo. ICS patients treated with FP100BID had a mean increase in morning peak expiratory flow (from baseline to end point) of 18 L/min compared with mean decreases of -3 L/min and -12 L/min in the FP200QD and placebo groups, respectively. More patients were withdrawn from placebo (26% and 48%, in BD and ICS patients, respectively) than from fluticasone propionate (7%-9% [BID-QD] and 18%-32% [BID-QD], in BD and ICS patients, respectively) because of failure to meet predetermined asthma stability criteria.\n The efficacies of FP100BID and FP200QD were comparable with regard to improvement in pulmonary function and asthma stability in BD patients. In ICS patients, asthma control was maintained with FP200QD, whereas FP100BID provided greater improvements in pulmonary function and asthma stability.", "Many patients with severe asthma are dependent on oral corticosteroids for maintenance control of their disease. Treatments that allow patients to be weaned off oral corticosteroids may help to minimize the risk of side effects associated with their chronic use.\n This study evaluated whether inhaled fluticasone propionate powder could maintain pulmonary function while reducing the dose of oral prednisone in patients with chronic, severe asthma.\n Oral prednisone-dependent (5 to 40 mg/day) adolescents and adults with asthma (n = 111; mean FEV1 = 61% of predicted value) were randomized to placebo or twice daily fluticasone propionate 500 or 1000 microg administered by means of a multidose powder inhaler for 16 weeks in a double-blind, parallel-group study. Patients underwent controlled prednisone reduction on the basis of predetermined asthma stability criteria.\n Oral prednisone was eliminated by 75% and 89% of patients in the twice daily 500 and 1000 microg fluticasone propionate groups, respectively, versus 9% of the placebo group (P <.001). FEV1, morning and evening peak expiratory flow, asthma symptoms, albuterol use, and nighttime awakenings improved with fluticasone propionate treatment, achieving statistical significance (P </=.009) primarily in the 1000 microg twice daily group. Hypothalamic-pituitary-adrenal axis suppression observed at baseline improved when patients were weaned off oral prednisone to fluticasone propionate. Adverse events ascribed to drug treatment were primarily topical effects of inhaled corticosteroids or those associated with prednisone withdrawal. Patient quality of life assessed by means of the Asthma Quality of Life Questionnaire was clinically and significantly improved after fluticasone propionate treatment (P </=.003).\n Fluticasone propionate powder (500 or 1000 microg twice daily) effectively improved lung function, adrenal function, and asthma-specific quality of life in patients with severe chronic asthma previously treated with oral prednisone while allowing most patients to be weaned off oral corticosteroid therapy.", "if patients with asthma remain symptomatic in spite of chronic treatment with inhaled corticosteroids (ICS), increasing the ICS dosage or adding another drug to the treatment regimen are possible therapeutic alternatives. We compared the efficacy and safety of combined salmeterol fluticasone therapy (SFC, 50/250 microg twice daily) with twice the dose of fluticasone propionate (FP, 500 microg b.i.d.) in symptomatic asthmatics.\n this prospective, double-blind study was conducted in 76 study centres. 365 symptomatic patients with moderate asthma aged >18 years and receiving ICS in a dose equivalent to 1000 microg beclomethasone propionate per day were randomly assigned to receive either salmeterol xinafoate (50 microg) and fluticasone propionate (250 microg) in a single dry powder inhaler (Diskus) or 500 microg FP twice daily. The primary efficacy endpoint was morning peak expiratory flow rate (PEFR). Secondary measurements included forced expiratory volume in 1 second (FEV1), asthma symptom scores, and use of rescue medication.\n combined salmeterol fluticasone therapy resulted in significantly greater improvements in PEFR and symptom control than doubling the dose of FP. At week 12, morning PEFR had increased by 52 L/min from baseline in patients on SFC and by 36 L/min in subjects receiving FP. The adjusted difference between groups was 16.6 L/min (95% confidence interval, 1.1 to 32.0 L/min). In the SFC group, the percentage of symptom-free days increased from baseline by 49% of days as compared with 38% of days after FP (adjusted difference: 12.6% of days, 95% CI 4.0 to 20.7). Quality of life improved to a greater degree after SFC therapy, and patients regarded study drugs as superior to their previous asthma medication. Adverse event profiles were similar between groups.\n the combination of salmeterol 50 microg and fluticasone 250 microg in a single dry powder inhaler was superior to twice the dose of FP (500 microg). It seems justified to add salmeterol rather than increasing the ICS dose if symptomatic asthmatics require supplementary therapy.", "This study compared the effect of inhaled fluticasone propionate (FP) with the combination of salmeterol/fluticasone propionate (SFC) on lung function parameters in patients with mild asthma.\n Adult patients with mild persistent asthma (> or = 80% predicted FEV1) receiving 200-500 mug of BDP or equivalent were randomised to receive either FP 100 mug or SFC 50/100 mug twice daily from a Diskus inhaler for four weeks. The primary outcome was the change from baseline in airway resistance (sRaw) at 12 hrs post dose measured by whole body plethysmography. Impulse oscillometry and spirometry were also performed.\n A comparison of the geometric mean sRaw at 12 hrs post dose in the SFC group to the FP group gave a ratio of 0.76 (0.66 - 0.89, p < 0.001) at week 2 and 0.81 (0.71 - 0.94, p = 0.006) at week 4. Similarly, significant results in favour of SFC for oscillometry measurements of resistance and reactance were observed. FEV1 was also significantly superior at week 2 in the SFC group (mean difference 0.16L, 95% CI; 0.03 - 0.28, p = 0.015), but not at week 4 (mean difference 0.17L, 95% CI -0.01 - 0.34, p = 0.060).\n SFC is superior to FP in reducing airway resistance in mild asthmatics with near normal FEV1 values. This study provides evidence that changes in pulmonary function in patients with mild asthma are detected more sensitively by plethysmography compared to spirometry\n NCT00370591.", "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.", "To compare the efficacies of medium-dose fluticasone propionate (FP), medium-dose triamcinolone acetonide (TAA), and combined low-dose FP plus salmeterol (SL).\n Randomized, double-blind, triple-dummy, multicenter, 12-week clinical trial.\n Allergy/respiratory care clinics.\n Six hundred eighty patients with asthma previously uncontrolled with low-dose inhaled corticosteroids.\n FP, 220 microg bid; TAA, 600 microg bid; or FP, 88 microg plus SL, 42 microg bid.\n Outcome measures included FEV1, peak expiratory flow (PEF), supplemental albuterol use, nighttime awakenings, asthma symptoms, and physician global assessment. Compared with TAA, 600 microg bid, treatment with FP 220, microg bid, significantly increased FEV1, morning and evening PEF, and percent symptom-free days, and significantly reduced rescue albuterol use, number of nighttime awakenings, and overall asthma symptom scores (p < or = 0.035). Improvements with low-dose FP, 88 microg, plus SL, 42 microg bid, were significantly (p < or = 0.004) greater than TAA, 600 microg bid, in all the aforementioned efficacy measures as well as percent of rescue-free days. Combined low-dose FP, 88 microg, plus SL, 42 microg bid, also significantly increased FEV1 and percent of rescue-free days, and significantly reduced albuterol use compared with medium-dose FP, 220 microg bid (p < or = 0.018). At endpoint, both FP, 220 microg bid, and FP, 88 microg, plus SL, 42 microg bid, significantly increased FEV1 by 0.48 L and 0.58 L, respectively, compared with 0.34 L with TAA, 600 microg bid.\n In patients who are symptomatic while taking low-dose inhaled corticosteroids, medium-dose FP (440 microg/d) and combination treatment with low-dose FP (176 microg/d) plus SL (84 microg/d) are both more effective than medium-dose TAA (1200 microg/d) in improving pulmonary function and asthma symptom control.", "Airway inflammation is now regarded as fundamental in the pathogenesis of asthma and treatment with inhaled corticosteroids has proved effective. There is a need for drugs in this category with higher topical potency but fewer side-effects than those presently available. A double-blind, parallel group study was conducted in 671 patients with severe asthma (already taking between 0.8-2.0 mg of inhaled corticosteroid daily) to compare the safety and efficacy of 6 weeks of treatment with inhaled fluticasone propionate (FP), 1 mg daily, to fluticasone propionate, 2 mg daily, and budesonide (BUD), 1.6 mg daily, delivered via a metered-dose inhaler. Peak expiratory flow (PEF), asthma symptoms, and usage of rescue medication were recorded daily by the patient. At each clinic visit (-2, 0, 3 and 6 weeks) morning serum cortisol levels, bone markers and spirometry were assessed. The changes in mean morning PEF from baseline (weeks 1-6) were: FP 2 mg daily +24 l.min-1; FP 1 mg daily +21 l.min-1; BUD 1.6 mg daily +13 l.min-1. A similar rank order for the three treatments was seen for evening PEF, clinic spirometry, reduction of diurnal PEF variation, symptom scores, and requirement for rescue bronchodilators. The mean serum cortisol levels remained well within the normal range in all three groups. Analysis of the geometric mean cortisol ratio (treatment/baseline ratio after 6 weeks treatment) showed a changed rank order, the values being: FP 1 mg daily 1.04; BUD 1.6 mg daily 0.97; FP 2 mg daily 0.88.(ABSTRACT TRUNCATED AT 250 WORDS)", "Guidelines state that oral and inhaled corticosteroids are the cornerstone of asthma treatment. The effect of both types of treatment can be assessed by measuring lung and systemic parameters. Treatment for two weeks with either oral prednisolone (30 mg/day), high dose fluticasone propionate (2000 microg/day, FP2000), or lower dose FP (500 microg/day, FP500), both given by a dry powder inhaler, were compared.\n One hundred and twenty patients with asthma were treated for two weeks in a double blind parallel group design. Lung function, asthma symptoms, airway hyperresponsiveness (PC(20) methacholine and adenosine-5'-monophosphate), sputum eosinophil and eosinophilic cationic protein (ECP) levels were measured as lung parameters. In addition, morning serum blood cortisol, blood eosinophil, and serum ECP levels were measured as systemic parameters.\n PC(20) methacholine and adenosine-5'-monophosphate showed significantly greater improvement with FP2000 (1.99 and 4.04 doubling concentrations (DC), respectively) than prednisolone (0.90 DC, p = 0.02; 2.15 DC, p = 0. 05) and marginally more than with FP500 (1.69 and 3.54 DC). Changes in sputum eosinophil and ECP concentrations showed similar trends; the decrease in ECP was significantly greater with FP2000 than with FP500. In contrast, the systemic parameters of steroid activity (cortisol, peripheral blood eosinophils, and serum ECP) decreased to a similar extent with FP2000 and prednisolone but significantly less with FP500.\n Oral prednisolone (30 mg/day) was inferior to FP2000 in improving airway hyperresponsiveness to both methacholine and AMP, with similar trends in forced expiratory volume in one second (FEV(1)), sputum eosinophil and ECP concentrations. Systemic effects were similar with prednisolone and FP2000 and less with FP500.", "Three hundred and fifty-three asthmatic patients who remained symptomatic despite treatment with budesonide 800-1200 microg day(-1) (or equivalent) were randomized to a new combination therapy comprising salmeterol 50 microg and fluticasone propionate 250 microg (Seretide, Advair, Viani 50/250 microg) twice daily or budesonide 800 microg twice daily for 24 weeks. Patients kept daily records of their morning and evening peak expiratory flow (PEF), daytime and night-time symptom scores and daytime and night-time use of rescue salbutamol. Mean morning PEF increased by 451 min(-1) (baseline 361 l min(-1)) in the salmeterol/fluticasone propionate combination (SFC) group and by 19 l min(-1) (baseline 358 l min(-1)) in the budesonide group over the 24 weeks. The adjusted mean morning PEF over weeks 1 to 24 was significantly greater in the SFC group, despite the > three-fold lower corticosteroid dose (406 vs. 380 l min(-1); P < 0.001). A significantly greater improvement in evening PEF was also seen in the SFC group (adjusted mean 416 vs. 398 l min(-1); P<0.001). SFC also provided significantly better control of daytime symptoms and a significantly greater reduction in the requirement for rescue salbutamol compared with budesonide. These results demonstrate that SFC 50/250 microg twice daily is superior to budesonide 800 microg twice daily in the management of patients with moderate to severe asthma who are symptomatic on their existing dose of corticosteroid.", "Oral corticosteroids used in short courses for acute asthma are regarded as safe, although the frequent use of these drugs may result in patients suffering from systemic side effects. It has become common practice for patients to increase their own inhaled corticosteroid intake when their asthma goes out of control, but it has never been established whether a high dose of inhaled corticosteroid can be as effective as a short course of oral corticosteroid in the treatment of acute exacerbations.\n A multicentre, randomised, double blind, double dummy, parallel group study was undertaken to determine whether the introduction of a high dose of inhaled fluticasone propionate (2 mg daily) is as effective as a short reducing course of oral prednisolone (starting at 40 mg/day and reducing by 5 mg every other day) in the treatment of acute exacerbations of asthma not considered severe enough for admission to hospital but requiring treatment with oral corticosteroid.\n Four hundred and thirteen adult asthmatic subjects who presented to their general practitioner with an acute exacerbation of asthma were recruited in 47 general practices in the United Kingdom. Treatment failures, defined as a reduction in peak expiratory flow (PEF) to below 60% of the patient's best/predicted value on two consecutive occasions or persistent symptoms with no improvement on three consecutive days, occurred in 23% of patients who received oral prednisolone and 27% who received inhaled fluticasone propionate (difference in percentage of treatment failures 4.3, 95% CI -4.1 to 12.8, p = 0.31). In each group 48% were classified as treatment successes, defined as a 10% or greater increase in percentage best/predicted morning PEF. Both treatments were equally well tolerated.\n There is no evidence of a significant difference in efficacy between a reducing dose course of oral prednisolone and high dose inhaled fluticasone propionate in mild exacerbations of asthma which do not require admission to hospital.", "A single high dose of inhaled corticosteroid (ICS) can increase airway caliber in children with asthma attacks and laryngitis subglottica. Presumably the effect is due to the vasoconstrictive and antiedematous properties of topical steroids. Enlarged vessels have been suggested to play a role in the pathophysiology of exercise-induced bronchial obstruction (EIB). To investigate this, we evaluated the effect of a single high dose of fluticasone propionate (FP) on EIB in asthmatic children. Nine children aged 8-16 years with mild to moderate asthma were included. All children had a history of EIB, which was confirmed by an exercise test. None was taking ICS maintenance therapy. The children inhaled either a single dose of 1 mg FP or placebo on 2 separate days within 7-14 days. After inhalation, airway caliber (FEV(1)) was assessed for 4 hr before exercise. Then an exercise challenge was performed on a treadmill to assess EIB (% fall FEV(1)). A significant increase in FEV(1) was observed 1 hr after inhalation of FP compared to placebo. Response to exercise was expressed as maximal % fall in FEV(1) from baseline (% fall) and as area under the curve (AUC) of the 30-min time/response curve. The % fall FEV(1) after exercise and the AUC were significantly reduced when FP was inhaled compared to placebo inhalation (% fall 9.7% vs. 19.2%, respectively, P = 0.038 and AUC 92.0%.min vs. 205.7%.min, respectively, P = 0.03). There was considerable individual variability in reduction of EIB, with 5 out of 9 children having a clinically significant response. We conclude that a single high dose of inhaled FP has an acute protective effect on the bronchial response to exercise in a substantial proportion of asthmatic children.\n Copyright 2001 Wiley-Liss, Inc.", "Inhaled corticosteroids are considered to be effective and safe to treat children with asthma. These drugs, often used as maintenance treatment, can, however, influence the HPA-axis, which might be reflected by the serum and urine cortisol concentration. The aim of the present study was to investigate the efficacy and safety of fluticasone propionate (FP) 100 microg administered twice a day via a Diskhaler for 3 mo. FP was tested in a double-blind randomized placebo-controlled parallel trial in a group of 34 children with moderate asthma who did not use inhaled steroids for at least 4 wk prior to the study. At home, symptoms and peak flow recordings (PEFR) were noted in a diary. At each visit lung function was measured, and serum and urinary cortisol were determined. During treatment, wheezing decreased and PEFR values increased in the FP group. FEV1 and PC20-histamine increased and the reversibility decreased in the FP group. All changes were significant, with the exception of the change in nocturnal PEFR. Four weeks after cessation of FP all parameters returned to pretreatment values. Serum cortisol did not change significantly in either treatment group. The decrease in urinary cortisol in the FP group was significant only if it was compared with the increase in urinary cortisol in the placebo group. We conclude that FP 100 microg given twice a day is effective in children with moderate stable asthma. Suppression of the HPA-axis by FP 100 microg given twice daily, although not likely, cannot be ruled out by this study since the absence of a significant decrease in urinary cortisol in the FP group could be due to an insufficient number of patients. Additional studies are required to solve this problem.", "Inhaled corticosteroids are effective in the treatment of children with asthma. It is uncertain how inhaled corticosteroids compare with oral corticosteroids in the management of severe acute disease.\n We performed a double-blind, randomized trial involving 100 children five years of age or older who had severe acute asthma (indicated by a forced expiratory volume in one second [FEV1] that was less than 60 percent of the predicted value) and in whom the results could be evaluated. All were treated with an aggressive bronchodilator regimen and received one dose of either 2 mg of inhaled fluticasone through a metered-dose inhaler with a spacer or 2 mg of oral prednisone per kilogram of body weight. They were assessed hourly for up to four hours.\n The mean (+/-SD) base-line FEV1 as a percentage of the predicted value was 46.3+/-12.5 in the fluticasone group (51 subjects) and 43.9+/-9.9 in the prednisone group (49 subjects). The FEV1 increased by a mean of 9.4+/-12.5 percentage points in the fluticasone group and by 18.9+/-9.8 percentage points in the prednisone group four hours after therapy (P< 0.001). None of the children in the prednisone group had a reduction in FEV1 as a percentage of the predicted value from base line to four hours, as compared with 25 percent of those in the fluticasone group (P<0.001). Sixteen (31 percent) of the children treated with fluticasone were hospitalized, as compared with five (10 percent) of those treated with prednisone (P=0.01).\n Children with severe acute asthma should be treated with oral prednisone and not with inhaled fluticasone or a similar inhaled corticosteroid.", "The use of inhaled corticosteroids compared with leukotriene modifying drugs in the treatment of persistent asthma has not been extensively studied.\n To compare the efficacy and safety of a low dose of fluticasone propionate (FP) and zafirlukast in patients previously maintained on inhaled corticosteroids.\n Patients (> or = 12 years old; FEV1 = 60% to 85% of predicted) with persistent asthma who were previously treated with low doses of triamcinolone acetonide (TAA) 400 to 800 microg/day or beclomethasone dipropionate (BDP) 168 to 336 microg/day were randomized to treatment with FP aerosol 88 microg BID (FP, n = 221) or zafirlukast 20 mg BID (n = 216) over 6 weeks.\n Treatment with FP significantly increased the mean change at endpoint (the last post-baseline observation) in FEV1 (0.22 L versus 0.03 L, P < .001), morning PEF (17.8 versus 3.1 L/min, P = .004), evening PEF (16.7 versus 2.6 L/min, P = .002), the percentage of symptom-free days (16.2 versus 7.1%, P = .007), and the percentage of rescue-free days (23.4 versus 9.3%, P < .001), and significantly decreased rescue albuterol use (-0.66 puffs/day versus an increase of 0.27 puffs/day, P < .001) and combined symptom scores (-0.13 versus an increase of 0.08, P < .001) compared with zafirlukast. Treatment with FP maintained the percentage of awakening-free nights (-1.0 +/- 1.0); in contrast, treatment with zafirlukast reduced the percentage of awakening-free nights (-9.0 +/- 1.6, P < .001). A clinically meaningful difference (change of > or = 0.5; P < .001) was observed between FP and zafirlukast in the Asthma Quality of Life Questionnaire (AQLQ) global score and for each domain score except activity limitation (change of 0.3, P < .001). Significantly more patients in the zafirlukast group experienced an asthma exacerbation (n = 14) compared with FP-treated patients (n = 5, P = .035). Patients in the zafirlukast group were significantly more likely to be withdrawn due to lack of efficacy (P < .001).\n Switching patients from low doses of inhaled corticosteroids to a lower total microgram dose of FP improves pulmonary function, asthma symptoms, and quality of life, while switching to the leukotriene receptor antagonist zafirlukast may result in worsening of asthma control. This was indicated by the significant number of zafirlukast-treated patients who were dropped from the study due to lack of efficacy within 6 weeks of discontinuing inhaled corticosteroids.", "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.", "To evaluate the efficacy and safety of fluticasone propionate administered as a once-daily or twice-daily regimen over a period of 1 year to patients with moderate asthma.\n Double-blind, randomized, parallel group, and placebo-controlled phase (12 weeks) and an open-label phase (54 weeks).\n Multicenter study in an outpatient setting.\n Patients (n = 253; age, > or = 12 years) with a mean FEV(1) of 67% predicted normal were stratified according to baseline therapy of maintenance inhaled corticosteroids vs beta(2)-agonists alone.\n Fluticasone propionate (250 microg bid or 500 microg qd) or placebo (bid) was administered via the Diskus multidose powder inhaler (Glaxo Wellcome; Research Triangle Park, NC) for 12 weeks. During open-label treatment, patients were re-randomized to once-daily or twice-daily fluticasone propionate.\n Compared to placebo, fluticasone propionate administered qd or bid significantly improved FEV(1) (p < 0.001), morning (p < 0.001) and evening peak expiratory flow (PEF; p < 0.001), asthma symptom scores (p < or = 0.001), and albuterol use (p </= 0.001), and decreased nighttime awakenings. By the end of 12 weeks, withdrawal due to lack of efficacy was significantly higher in the placebo group than in the once-daily (p = 0.001) or twice-daily (p < 0.001) groups. When comparing the two active dosing regimens, significant differences in favor of twice-daily dosing were noted in FEV(1), albuterol use, and withdrawal due to lack of efficacy. During 54 weeks of open-label treatment, FEV(1) and PEF continued to improve with both regimens, and improvements seen in the first 12 weeks were maintained in patients who switched from twice-daily to once-daily dosing. Fluticasone propionate treatment over a 54-week period was well tolerated, with few drug-related adverse events, which were primarily topical effects of inhaled corticosteroids.\n Fluticasone propionate powder improved lung function when administered either qd or bid over a 1-year period to patients with moderate asthma, with twice-daily dosing demonstrating significantly greater improvement in some efficacy parameters than once-daily dosing over the first 12 weeks of treatment. Fluticasone propionate treatment was not associated with significant systemic effects.", "It is important to be able to compare the efficacy and systemic effects of inhaled corticosteroids but their slow onset of action makes it difficult to measure the maximum response to a given dose. Submaximal responses could be compared if the time course of action of the inhaled corticosteroids being compared was similar. We have compared the time course of action of fluticasone and budesonide, measuring response as change in the provocative dose of adenosine monophosphate causing a 20% fall in forced expiratory volume in 1 second (PD20AMP).\n Eighteen subjects with mild asthma, aged 18-65, took part in a three way randomised crossover study. Subjects took fluticasone (1500 microg/day), budesonide (1600 microg/day), and placebo each for 4 weeks with a washout period of at least 2 weeks between treatments; PD20AMP and forced expiratory volume in 1 second (FEV1) were measured during and after treatment. The time taken to achieve 50% of the maximum response (T50%) was compared as a measure of onset of action.\n There was a progressive increase in PD20AMP during the 4 weeks of treatment with both fluticasone and budesonide but not placebo; the increase after 1 and 4 weeks was 2.28 and 4.50 doubling doses (DD) for fluticasone and 2.49 and 3.65 DD for budesonide. T50% was 9.3 days for fluticasone and 7.5 days for budesonide with a median difference between fluticasone and budesonide of 0.1 days (95% CI -1.4 to 2.65). There was a wide range of response to both inhaled corticosteroids but good correlation between the response to fluticasone and budesonide within subjects. FEV1 and morning peak expiratory flow rate (PEFR) increased during the first week of both active treatments and were stable thereafter. There was a small progressive improvement in nocturnal symptoms with both active treatments.\n PD20AMP was a more sensitive marker of response to inhaled corticosteroid therapy than FEV1 and PEFR. The time course of action of fluticasone and budesonide on PD20AMP is similar, suggesting that comparative studies of their efficacy using 1 or 2 week treatment periods are valid. When a new inhaled corticosteroid becomes available, a pilot study comparing its time course of action with that of an established corticosteroid should allow comparative studies to be performed more efficiently.", "In Vitro and in vivo data have demonstrated that there are detectable differences between inhaled corticosteroids commonly used to treat asthma. However, controversy still remains as to whether these differences translate into clinical benefits. This 12-week, international, randomized, doubleblind, parallel-group study was undertaken to compare the efficacy and safety of fluticasone propionate (FP) 800 mug daily, administered as a powder via the Diskhaler((R)), and budesonide (BUD) 1600 mug daily, administered using the Turbuhaler((R)), in adult patients with moderate-tosevere asthma. A total of 518 patients participated in the study, 256 of whom received FP and 262 BUD. Assessment of mean morning peak expiratory flow (PEF) over the 12-week treatment period revealed a statistically significant difference in efficacy between FP 800 mug daily and BUD 1600 mug daily in favour of FP (p = 0.003), with an overall improvement of 20.9 l/min with FP compared with 12.4 l/min on BUD. Statistically significant differences in favour of FP were seen over the 12 weeks for mean evening PEF (p = 0.04), diurnal PEF variation (p = 0.03) and percentage predicted PEF (p = 0.003), as well as forced expiratory volume (p = 0.008), forced vital capacity (p = 0.02) and PEF (p = 0.005) measured at clinic visits. The median percentage of symptom-free nights increased over the 12-week study period in both treatment groups, with similar changes seen for the median percentage of days with symptom score < 2, rescue medication use and exacerbations of asthma. The incidence of adverse events was found to be comparable in the two treatment groups. The geometric mean ratios of serum cortisol levels were found to be 1.03 for FP, indicating no mean hypothalamic-pituitary-adrenal axis suppression from baseline, and 0.93 for BUD (p = 0.0002 compared with FP). In summary, FP 800 mug daily showed a greater efficacy/safety ratio in the treatment of moderate-to-severe asthma than BUD 1600 mug daily.", "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.", "Inhaled corticosteroids are recommended for the treatment of persistent asthma. Comparative clinical studies evaluating 2 or more doses of these agents are few.\n We sought to compare the efficacy and safety of 2 doses of fluticasone propionate (88 micrograms twice daily and 220 micrograms twice daily) with 2 doses of beclomethasone dipropionate (168 micrograms twice daily and 336 micrograms twice daily) in subjects with persistent asthma.\n Three hundred ninety-nine subjects participated in this randomized, double-blind, parallel-group clinical trial. Eligible subjects were using daily inhaled corticosteroids and had an FEV1 of 45% to 80% of predicted value. Clinic visits, including spirometry, were conducted every 1 to 2 weeks. Subjects recorded symptoms, use of albuterol, and peak expiratory flows on daily diary cards.\n Fluticasone propionate treatment resulted in significantly (P </=.034) greater improvements in objective pulmonary function parameters than did beclomethasone dipropionate treatment and significantly greater reductions in daily albuterol use (P </=.010) and asthma symptoms (P </=.027). Both low-dose (88 micrograms twice daily) and medium-dose (220 micrograms twice daily) fluticasone propionate significantly increased FEV1 compared with higher doses of beclomethasone dipropionate (P =. 006). Low-dose and medium-dose fluticasone propionate improved FEV1 by 0.31 L (14%) and 0.36 L (15%), respectively, compared with improvements of 0.18 L (8%) and 0.21 L (9%) with low-dose and medium-dose beclomethasone dipropionate. The adverse event profiles were similar for both medications.\n Fluticasone propionate provides greater asthma control at roughly half the dose of beclomethasone dipropionate, with a comparable adverse event profile." ]	We have not found evidence of a pronounced dose response in FEV1 with increasing doses of fluticasone. The number of studies contributing to our primary outcomes was low. At dose ratios of 1:2, there are statistically significant differences in favour of the higher dose in morning peak flow across the low dose range. The clinical impact of these differences is open to interpretation. Patients with moderate disease achieve similar levels of asthma control on medium doses of fluticasone (400 to 500 µg/day) as they do on high doses (800 to 1000 µg/day). More work in severe asthma would help to confirm that doses of FP above 500 µg/day confer greater benefit in this subgroup than doses of around 200 µg/day. In oral corticosteroid-dependent asthmatics, reductions in prednisolone requirement may be gained with FP 2000 µg/day.
CD005122	[ "12583945", "7052117", "11408301" ]	[ "Admission cardiotocography: a randomised controlled trial.", "The value of antenatal cardiotocography in the management of high-risk pregnancy: a randomized controlled trial.", "Randomised controlled trial of cardiotocography versus Doppler auscultation of fetal heart at admission in labour in low risk obstetric population." ]	[ "Admission cardiotocography is widely used to identify pregnancies that might benefit from continuous electronic fetal monitoring in labour. We aimed to compare the effect on neonatal outcome of admission cardiotocography versus intermittent auscultation of the fetal heart rate.\n 8580 women admitted to the delivery ward of a Dublin teaching hospital who were at low risk of fetal distress in labour were randomly assigned admission cardiotocography (20 min) or the unit's usual care (intermittent auscultation only, with continuous cardiotocography only if clinically indicated). The primary outcome was moderate to severe neonatal morbidity, or perinatal mortality in the absence of a major congenital malformation. Analyses were by intention to treat.\n 44 (1.0%) women assigned admission cardiotocography did not undergo the procedure; 15 (0.4%) assigned usual care had admission cardiotocography. The primary endpoint occurred in 56 (1.3%) of 4298 women assigned admission cardiotocography and 55 (1.3%) of 4282 in the usual-care group (relative risk 1.01; 95% CI 0.70-1.47). Other indices of neonatal morbidity also showed no differences. Despite an increase in use of continuous cardiotocography (1.39; 1.33-1.45) and fetal blood sampling (1.30; 1.14-1.47) with admission cardiotocography, there were no significant differences in the rates of caesarean delivery (1.13; 0.92-1.40), instrumental delivery (1.03; 0.92-1.16), or episiotomy (1.06; 0.99-1.13).\n Routine use of cardiotocography for 20 min on admission to the delivery ward does not improve neonatal outcome. No significant increase in operative delivery was apparent, probably because of liberal use of fetal blood sampling.", "The value of routine regular antenatal cardiotocography (CTG) in the management of high-risk pregnancy was assessed in a prospective randomized controlled study of 353 patients. All patients had a weekly CTG trace during the last 6 weeks of pregnancy and according to the random allocation the tracings were concealed from, or available to, the clinicians. Other methods of assessing fetal welfare were available to both groups. There was no significant difference between the concealed and revealed groups in the timing and mode of delivery, birthweights, Apgar score and neonatal morbidity. No apparent effect from the routine use of antenatal CTG in high-risk pregnancy was shown.", "To compare the effect of admission cardiotocography and Doppler auscultation of the fetal heart on neonatal outcome and levels of obstetric intervention in a low risk obstetric population.\n Randomised controlled trial.\n Obstetric unit of teaching hospital\n Pregnant women who had no obstetric complications that warranted continuous monitoring of fetal heart rate in labour.\n Women were randomised to receive either cardiotocography or Doppler auscultation of the fetal heart when they were admitted in spontaneous uncomplicated labour.\n The primary outcome measure was umbilical arterial metabolic acidosis. Secondary outcome measures included other measures of condition at birth and obstetric intervention.\n There were no significant differences in the incidence of metabolic acidosis or any other measure of neonatal outcome among women who remained at low risk when they were admitted in labour. However, compared with women who received Doppler auscultation, women who had admission cardiotocography were significantly more likely to have continuous fetal heart rate monitoring in labour (odds ratio 1.49, 95% confidence interval 1.26 to 1.76), augmentation of labour (1.26, 1.02 to 1.56), epidural analgesia (1.33, 1.10 to 1.61), and operative delivery (1.36, 1.12 to 1.65).\n Compared with Doppler auscultation of the fetal heart, admission cardiotocography does not benefit neonatal outcome in low risk women. Its use results in increased obstetric intervention, including operative delivery." ]	Contrary to continued use in some clinical areas, we found no evidence of benefit for the use of the admission cardiotocograph (CTG) for low-risk women on admission in labour. We found no evidence of benefit for the use of the admission CTG for low-risk women on admission in labour. Furthermore, the probability is that admission CTG increases the caesarean section rate by approximately 20%. The data lacked power to detect possible important differences in perinatal mortality. However, it is unlikely that any trial, or meta-analysis, will be adequately powered to detect such differences. The findings of this review support recommendations that the admission CTG not be used for women who are low risk on admission in labour. Women should be informed that admission CTG is likely associated with an increase in the incidence of caesarean section without evidence of benefit.
CD003936	[ "1320133", "9709043" ]	[ "Efficacy of nonoxynol 9 contraceptive sponge use in preventing heterosexual acquisition of HIV in Nairobi prostitutes.", "A controlled trial of nonoxynol 9 film to reduce male-to-female transmission of sexually transmitted diseases." ]	[ "To determine the efficacy of the nonoxynol 9 contraceptive sponge in preventing sexual acquisition of the human immunodeficiency virus (HIV).\n Prospective, randomized placebo-controlled trial.\n Research clinic for prostitutes in Nairobi, Kenya.\n One hundred thirty-eight HIV-seronegative women were enrolled, of whom 74 were assigned to nonoxynol 9 sponge use and 64 to placebo use. These two groups did not significantly differ with respect to demographic characteristics, sexual practices, or prevalence of genital infections at enrollment, except for a lower number of sex partners per week and a higher initial prevalence of genital ulcers among women assigned to nonoxynol 9 sponge use. Among the 116 women who returned for follow-up, the mean durations of follow-up were 14 and 17 months for the two groups, respectively.\n HIV seroconversion.\n Nonoxynol 9 sponge use was associated with an increased frequency of genital ulcers (relative risk [RR], 3.3; P less than .0001) and vulvitis (RR, 3.3; P less than .0001) and a reduced risk of gonococcal cervicitis (RR, 0.4; P less than .0001). Twenty-seven (45%) of 60 women in the nonoxynol 9 sponge group and 20 (36%) of 56 women in the placebo group developed HIV antibodies. The hazard ratio for the association between nonoxynol 9 sponge use and HIV seroconversion was 1.7 (95% confidence interval [CI], 0.9 to 3.0). Using multivariate analysis to control for the presence of genital ulcers at enrollment, the adjusted hazard ratio for the association between nonoxynol 9 sponge use and seroconversion was 1.6 (95% CI, 0.8 to 2.8).\n Genital ulcers and vulvitis occurred with increased frequency in nonoxynol 9 sponge users. We were unable to demonstrate that nonoxynol 9 sponge use was effective in reducing the risk of HIV infection among highly exposed women.", "Nonoxynol 9 is a proved spermicide, but whether it is also a microbicide is uncertain. A truly effective vaginal microbicide would reduce the susceptibility of women to sexually transmitted diseases, including infection with the human immunodeficiency virus (HIV).\n We enrolled 1292 HIV-negative female sex workers in Cameroon and enrolled them in a double-blind, placebo-controlled study in which the participants were randomly assigned to use either a film containing 70 mg of nonoxynol 9 or a placebo film, inserted into the vagina before intercourse. All of the women were provided with latex condoms and were instructed to have their male sexual partners use them. At monthly follow-up visits, we examined the women with a colposcope for genital lesions, tested endocervical specimens for gonorrhea and chlamydia infection with DNA probes, tested for HIV infection, and treated the women for curable sexually transmitted diseases.\n The rates of HIV infection (cases per 100 woman-years) were 6.7 in the nonoxynol 9 group and 6.6 in the placebo group (rate ratio, 1.0; 95 percent confidence interval, 0.7 to 1.5). The rates of genital lesions were 42.2 cases per 100 woman-years in the nonoxynol 9 group and 33.5 in the placebo group (rate ratio, 1.3; 95 percent confidence interval, 1.0 to 1.6). The rates of gonorrhea were 33.3 and 31.1 cases per 100 woman-years in the nonoxynol 9 and placebo groups, respectively (rate ratio, 1.1; 95 percent confidence interval, 0.8 to 1.4). The corresponding rates of chlamydia infection in the nonoxynol 9 group and the placebo group were 20.6 and 22.2 per 100 woman-years (rate ratio, 0.9; 95 percent confidence interval, 0.7 to 1.3). The women reported that condoms were used during 90 percent of sexual acts.\n The use of a nonoxynol 9 vaginal film did not reduce the rate of new HIV, gonorrhea, or chlamydia infection in this group of sex workers who used condoms and received treatment for sexually transmitted diseases." ]	There is no evidence that nonoxynol-9 protects against vaginal acquisition of HIV infection by women from men. There is evidence that it may do harm by increasing the frequency of genital lesions.
CD000947	[ "16962532", "19187377", "20680312", "2558705", "18271883", "12103284", "18506347", "3011061", "2030849", "6351265", "12842060", "9609272", "9740522" ]	[ "A randomized comparison of suturing techniques for episiotomy and laceration repair after spontaneous vaginal birth.", "Continuous versus interrupted sutures for repair of episiotomy or second-degree perineal tears: a randomised controlled trial.", "Continuous versus interrupted episiotomy repair with monofilament or multifilament absorbed suture materials: a randomised controlled trial.", "The Southmead perineal suture study. A randomized comparison of suture materials and suturing techniques for repair of perineal trauma.", "Postpartum perineal repair performed by midwives: a randomised trial comparing two suture techniques leaving the skin unsutured.", "Continuous versus interrupted perineal repair with standard or rapidly absorbed sutures after spontaneous vaginal birth: a randomised controlled trial.", "Randomized controlled clinical trial on two perineal trauma suture techniques in normal delivery.", "Episiotomy repair--immediate and long-term sequelae. A prospective randomized study of three different methods of repair.", "A randomized study of closure of the peritoneum at cesarean delivery.", "Abdominal incisions: transverse vs vertical placement and continuous vs interrupted closure.", "Does perineal suturing make a difference? The SUNS trial.", "The Ipswich Childbirth Study: 1. A randomised evaluation of two stage postpartum perineal repair leaving the skin unsutured.", "Closure versus non-closure of peritoneum at cesarean section--evaluation of pain. A randomized study." ]	[ "To compare the continuous knotless technique of perineal repair with the interrupted method after spontaneous vaginal birth\n A randomized controlled trial.\n Canadian Task Force Classification I.\n This study was undertaken in a university hospital with more than 2200 deliveries per year. The static population of this district includes a wide range of socioeconomic classes and is predominately white.\n From May 1 to November 19, 2003, 214 primiparous women with a second-degree perineal tear or episiotomy were randomly allocated to either the continuous knotless technique (CKT; n=107) or the interrupted technique (IT; n=107) suturing method.\n The interrupted technique (IT) involves placing 3 layers of sutures whereas the continuous knotless technique (CKT) involves reapproximating vaginal trauma, perineal muscles, and skin with a loose, continuous, nonlocking technique.\n The primary outcomes of the study were perineal pain (evaluated by visual analogue scale) at 48 hours and day 10 and dyspareunia 3 months after delivery. Secondary outcomes included suture removal, wound dehiscence, analgesia use up to 48 hours, and satisfaction with repair established at 3 and 12 months after childbirth. At day 10, 19 women had dropped out of the study. Significantly fewer women reported pain at 10 days with the CKT than with the IT (32.3% vs 60.4%; p<.001). Analgesia use up to 48 hours postpartum was less in the CKT group than in the IT group (33.6% vs 54.2%; p<.05). No difference was found in superficial dyspareunia at 3 months for the CKT versus the IT group.\n The use of a continuous knotless technique for perineal repair is associated with less short-term pain than techniques with interrupted sutures.", "To evaluate the repair techniques of continuous and interrupted methods for episiotomy or perineal tears.\n A randomised controlled trial.\n The Hospital Universitario Principe de Asturias, a state hospital belonging to the community of Madrid.\n Four hundred forty-five women who had undergone vaginal deliveries with episiotomies or second-grade tearing of the perineum between September 2005 and July 2007.\n One group was repaired with continuous, nonlocking sutures involving the vagina, perineum, and subcutaneous tissues. The other group had continuous, locking sutures of the vagina, interrupted sutures in the perineal muscles, and interrupted transcutaneous sutures. The threads used for stitching were identical in both groups.\n The participants were questioned regarding the sensation of pain and the use of painkillers on the second and the tenth days, and 3 months postpartum.\n When comparing the group with continuous suture to the group with interrupted sutures, the differences included less repair time (1 minute; P= 0.017) and less suture material used (relative risk [RR], 3.2, 95% CI: 2.6-4.0). The comparison of pain on the second and tenth days, and 3 months postpartum were not statistically different between the two techniques (RR, 1.08, 95% CI: 0.74-1.57; RR, 0.96, 95% CI: 0.59-1.55; and RR, 0.68, 95% CI: 0.19-2.46, respectively).\n Although we did not demonstrate that one technique was better than the other in the incidence of pain in the short or long term, we showed that episiotomy and perineal tear repairs with continuous suturing were quicker and used less suture material without an increase in complication than interrupted suturing.", "To compare different repair techniques and different suture materials for episiotomy.\n 160 women having vertex delivery with right-mediolateral episiotomy were randomly allocated to four groups. In the groups where continuos technique was performed, vaginal mucosa, perineal muscles and the skin were sutured continuously. In the groups of interrupted technique, vaginal mucosa was sutured with continuous sutures, then muscle layers and skin were closed by interrupted sutures. Two different types of synthetic absorbed suture material were used: monofilament type is in form of polyglycolide-co-caprolactone and multifilament one is polyglactin 910-Rapide. Perineal pain during different activities on the first and tenth day postpartum and also during sexual intercourse 6 weeks after the delivery was questioned by visual analogous scale (VAS). Furthermore, repair time, amount of suture and episiotomy complications were investigated in each groups.\n On the first day after delivery, the perineal pain scores, the repair time, the amount of suture were statistically less in the continuous technique groups. The differences between the pain at tenth day and during sexual intercourse 6 weeks after the delivery were statistically same.\n The continuous suturing techniques for episiotomy closure, compared to interrupted methods, are associated with less short-term pain, are quicker and also need less suture material.", "Commonly used suture materials and techniques for perineal repair following vaginal delivery were compared in a randomized controlled trial involving 1574 women. Three comparisons were made using a modified factorial design. In the comparison of teflon-coated polyglycolic acid (Dexon plus) with chromic catgut for repair of the vagina and deep perineal tissues there was no clear difference other than less short-term analgesia being required in association with polyglycolic acid. Outcome was also similar after skin repair with either polyglycolic acid or chromic catgut or silk, although silk repair required more packets of material and was associated with delay in resuming sexual intercourse; polyglycolic acid was more likely to need removal than chromic catgut but it appeared to reduce the need for resuturing. There was no clear difference between continuous subcuticular and interrupted transcutaneous sutures for repair of perineal skin.", "To compare a continuous suture technique with interrupted stitches using inverted knots for postpartum perineal repair of second-degree lacerations and episiotomies.\n A double-blind randomised controlled trial.\n A Danish university hospital with more than 4800 deliveries annually.\n A total of 400 healthy primiparous women with a vaginal delivery at term. METHOD Randomisation was computer-controlled. Structured interviews and systematic assessment of perineal healing were performed by research midwives blinded to treatment allocation at 24-48 hours, 10 days and 6 months postpartum. Pain was evaluated using a visual analogue scale and the McGill Pain Questionnaire. Wound healing was evaluated using the REEDA scale and by assessment of gaping wounds >0.5 cm. Analysis complied with the intention-to-treat principle.\n The primary outcome was perineal pain 10 days after delivery. Secondary outcomes were wound healing, patient satisfaction, dyspareunia, need for resuturing, time elapsed during repair and amount of suture material used.\n A total of 400 women were randomised; 5 women withdrew their consent, leaving 395 for follow up. The follow-up rate was 98% for all assessments after delivery. No difference was seen in perineal pain 10 days after delivery. No difference was seen in wound healing, patient satisfaction, dyspareunia or need for resuturing. The continuous suture technique was significantly faster (15 versus 17 minutes, P = 0.03) and less suture material was used (one versus two packets, P < 0.01).\n Interrupted, inverted stitches for perineal repair leaving the skin unsutured appear to be equivalent to the continuous suture technique in relation to perineal pain, wound healing, patient satisfaction, dyspareunia and need for resuturing. The continuous technique, however, is faster and requires less suture material, thus leaving it the more cost-effective of the two techniques evaluated.", "Trauma to the perineum is a serious and frequent problem after childbirth, with about 350000 women each year in the UK needing sutures for perineal injury after spontaneous vaginal delivery, and many millions more worldwide. We compared the continuous technique of perineal repair with the interrupted method, and the more rapidly absorbed polyglactin 910 suture material with the standard polyglactin 910 material.\n 1542 women who had a spontaneous vaginal delivery with a second-degree perineal tear or episiotomy were randomly allocated to either the continuous (n=771) or interrupted (771) suturing method, and to either the more rapidly absorbed polyglactin 910 suture material (772) or standard polyglactin 910 material (770). Primary outcomes were pain 10 days after delivery and superficial dyspareunia 3 months postpartum. Analysis was by intention to treat.\n At day 10, three women had dropped out of the study. Significantly fewer women reported pain at 10 days with the continuous technique than with the interrupted method (204/770 [26.5%] vs 338/769 [44.0%], odds ratio 0.47, 95% CI 0.38-0.58, p<0.0001). Occurrence of pain did not differ significantly between groups assigned the more rapidly absorbed material or standard material (256/769 [33.3%] vs 286/770 [37.1%], 0.84, 0.68-1.04, p=0.10). Women reported no difference in superficial dyspareunia at 3 months for the continuous vs the interrupted method (98/581 [16.9%] vs 102/593 [17.2%], 0.98, 0.72-1.33, p=0.88) or the more rapidly absorbed versus standard material (105/586 [17.9%] vs 95/588 [16.2%], 1.13, 0.84-1.54, p=0.42). Suture removal was done less with the more rapidly absorbed material than with standard suture material (22/769 [3%] vs 98/770 [13%], p<0.0001), and with the continuous versus interrupted method (24/770 [3%] vs 96/769 [12%], p<0.0001).\n A simple and widely practicable continuous repair technique can prevent one woman in six from having pain at 10 days. Also, the more rapidly absorbed polyglactin 910 material obviates need for suture removal up to 3 months postpartum for one in ten women sutured.", "The aim was to compare healing and perineal pain with the use of continuous and interrupted suture techniques in women after normal delivery. A randomized controlled trial was carried out at a hospital birth center in Itapecirica da Serra, Sao Paulo, Brazil. A total of 61 women participated with episiotomy or second degree perineal tear, allocated in two groups according to the continuous (n=31) or interrupted (n=30) suture techniques. The main outcomes evaluated were edema, ecchymosis, hyperemia, secretion, dehiscence, fibrosis, frequency and degree of pain (evaluated by numerical scale from 1 to 10). Data were collected during hospitalization and after discharge (four and 41 days after birth). Healing occurred by first intention in 100% of cases in both suture techniques. There were no statistically significant differences for the occurrence of morbidities, except for perineal pain due to palpation at four days after delivery, which was more frequent among women with interrupted suture.", "Three methods of episiotomy repair were randomly assigned after 900 consecutive deliveries. The three procedures were: (1) continuous No. 00-plain catgut in the vagina; No. 00-plain catgut interrupted stitches in the perineal muscles and fascia, and No. 00-nylon interrupted stitches in the skin. (2) The same technique as in (1), but with No. 0-polyglycolic acid (Dexon) in all layers. (3) The suture material as in (2), but used with a subcuticular technique. The women treated with method 3 reported statistically significant less pain and disabilities in the early puerperium. Three months after delivery 262 women (33%) still had perineal complaints which could be directly related to the episiotomy in 25% (8% of total number). The group treated with method 3 had the best long-term results and we conclude that the subcuticular technique using polyglycolic acid should be the method of choice.", "This study was conducted to test the hypothesis that nonclosure of the visceral and parietal peritoneum during low transverse cervical cesarean delivery is not associated with increased intraoperative or immediate postoperative complications. One hundred thirteen patients scheduled for low transverse cervical cesarean were randomized to either closure of both the visceral and parietal peritoneum with absorbable suture (N = 59) or no peritoneal closure (N = 54). Patients were cared for in the usual postoperative manner without reference to treatment group. There were no demographic differences between the groups and no differences in method(s) of anesthesia, operative indication(s), or use of peripartum epidural narcotics. The incidence of fever, endometritis, or wound infection was similar between groups. There were no differences in the number of patients requiring parenteral narcotic analgesia or in the number of doses per patient. The number of oral analgesic doses was significantly greater with closure than without (P = .014). The frequency with which postoperative ileus was diagnosed in each group was similar, and there was no difference regarding the day on which patients were advanced to liquid or select diets. Bowel stimulants were administered more frequently to the closure than to non-closure patients (P = .03). The average operating time was shorter for the open group than for the closure group (P less than .005). We conclude that non-closure of the visceral and parietal peritoneum at low transverse cervical cesarean delivery appears to have no adverse effect on immediate postoperative recovery, may decrease postoperative narcotic requirements, allows less complicated return of bowel function, and provides a simplified and shorter surgical procedure.", "A previous retrospective review of 2,006 emergency laparotomies had suggested that anesthesia and operative times could be reduced by using a continuous stitch closure for all layers of the incision. A prospective, randomized study was then implemented through use of odd/even digits in the last and next-to-last digits in the hospital number. Of 551 patients subjected to laparotomy because of abdominal trauma, no intraperitoneal injury was found in 212. There was no statistically significant difference in time expended or complications (wound or other, including pulmonary) on contrasting transverse (101) with vertical (111) incisions, or on comparing continuous (104) and interrupted (108) closure, with the exception of an average 26 minutes in time saved by a continuous suture (P = .02). Analysis of these same factors in 339 patients with trauma found at laparotomy could document no statistically significant difference. Such data support the use of a running suture for closure of the abdominal wall as a practical method to save anesthesia and operating time without increased risk of developing a wound or other postoperative complication.", "To examine differences in outcome between primiparous women who do and who do not have suturing to first or second degree perineal lacerations sustained during spontaneous vaginal births after 37 weeks of gestation.\n Parallel group randomised controlled trial.\n Bellshill Maternity Hospital, Lanarkshire, and St John's Hospital, Livingston.\n Primigravidae with perineal lacerations following spontaneous birth.\n One thousand and three hundred fourteen women were recruited to the trial antenatally from whom 74 were randomised either to be sutured or not sutured immediately after giving birth. Randomisation was stratified by degree of tear.\n Using standardised measures, perineal pain and healing were measured at 1 and 10 days and 6 weeks postpartum. In addition, postnatal depression was assessed at 10 days and 6 weeks postpartum.\n Findings indicated that there were no significant differences between the groups with regard to pain or depression but there were differences with regard to healing. At six weeks, there remained a significant difference in wound closure between the groups, with women who had not been sutured having poorer wound approximation.\n While acknowledging the small sample size, the results are nonetheless important, showing persistent evidence of poorer wound approximation in those women who had not been sutured. Practitioners need to review the present practices of not suturing perineal lacerations until research examining the longer term implications is undertaken.", "To evaluate a policy of two stage postpartum perineal repair leaving the skin unsutured.\n A stratified randomised controlled trial using a 2 x 2 factorial design.\n The maternity unit at Ipswich Hospital NHS Trust, a district general hospital, between 1992 and 1994.\n 1780 women requiring surgical repair of episiotomy or first or second degree tear following a spontaneous or simple instrumental delivery.\n A policy of two-stage perineal repair leaving skin unsutured was compared with a policy of three stage repair including skin closure with interrupted or subcuticular sutures. Both groups were assessed by a research midwife, blind to the allocation, completing questionnaires at 24 to 48 hours and 10 days postpartum, and by self-completed questionnaires at three months after birth.\n 1. 24 to 48 hours postpartum: perineal pain; healing; 2. 10 days postpartum: perineal pain, healing and removal of sutures; 3. three months postpartum: perineal pain, removal of sutures, resuturing, dyspareunia, and failure to resume pain-free intercourse.\n Completed questionnaires were returned for 99% of women at both 24 to 48 hours and ten days and by 93% of women three months postpartum. No differences were detected in perineal pain at 24 to 48 hours (62% vs 64%; RR 0.96, 95% CI 0.90-1.03; 2P = 0.3) and 10 days (25% vs 28%; RR 0.90, 95% CI 0.77-1.06; 2P = 0.2). Significantly fewer women allocated to two-stage repair reported tight stitches at ten days (14% vs 18%; RR 0.77, 95% CI 0.62-0.96, 2P = 0.02); similar numbers of repairs were judged to be breaking down (five compared with seven women). At three months postpartum fewer women allocated to the two-stage repair reported perineal pain and more had resumed pain-free intercourse. Amongst women who had resumed intercourse there was a significant difference in dyspareunia (15% vs 19%; RR 0.80, 95% CI 0.65-0.99; 2P = 0.04). Significantly fewer women in the two-stage repair group (7% vs 12%; RR 0.61, 95% CI 0.45-0.83; 2P = < 0.01) reported removal of suture material. Four women in the two-stage repair group had required resuturing, compared with nine allocated to the three-stage repair.\n Two-stage repair of perineal trauma leaving the skin unsutured appears to reduce pain and dyspareunia three months postpartum. There are no apparent disadvantages, in particular no evidence of an increased risk of breakdown of the repair and resuturing.", "To evaluate the effects of leaving the parietal peritoneum open at lower segment cesarean section (LSCS) measured by postoperative pain.\n A randomized, prospective and double-blind study.\n Department of Obstetrics and Gynecology, Aarhus University Hospital, Denmark.\n Forty women referred for an elective cesarean section were assigned to one of two groups: peritoneum open (n=21) or peritoneum closed (n=19).\n Pain was evaluated twice a day from the first to the fifth postoperative day by Visual Analog Scales.\n Postoperative pain. Other outcomes include usage of analgesics, bowel function, postoperative complications, and hospital stay.\n We found no overall difference in postoperative pain. A tendency to less pain was found in the non-closure group from the third postoperative day to the fifth postoperative day. No differences were found either in the incidence of postoperative complications, or the time to return of bowel function. Concerning opiate analgesics the non-closure group had a significantly higher use in the second postoperative 24-hour period, but in the remains of the registration period it was significantly lower. For oral analgesics no difference was found in the first 24-hour period, but in the remains of the period the non-closure group had a significantly lower use.\n The VAS-scales showed no difference in postoperative pain comparing closure to non-closure of the parietal peritoneum. However, the use of analgesics is lower in the non-closure group. We suggest leaving the parietal peritoneum open when performing LSCS." ]	The continuous suturing techniques for perineal closure, compared with interrupted methods, are associated with less short-term pain, need for analgesia and suture removal. Furthermore, there is also some evidence that the continuous techniques used less suture material as compared with the interrupted methods (one packet compared to two or three packets, respectively).
CD006237	[ "16675365", "17549228", "17492326", "15550800", "12906341", "11556409", "12096294", "15121348", "8857869", "8046193" ]	[ "Effectiveness of an intervention to reduce sickness absence in patients with emotional distress or minor mental disorders: a randomized controlled effectiveness trial.", "A cluster-randomised trial evaluating an intervention for patients with stress-related mental disorders and sick leave in primary care.", "A randomized trial of telemedicine-based collaborative care for depression.", "The effect of improving primary care depression management on employee absenteeism and productivity. A randomized trial.", "Integrating clinical nurse specialists into the treatment of primary care patients with depression.", "A randomised controlled trial of the outcome of health assessment of people aged 75 years and over.", "Intervention to improve psychological functioning for newly diagnosed patients with cancer.", "The impact of a pharmacist intervention on 6-month outcomes in depressed primary care patients.", "A multifaceted intervention to improve treatment of depression in primary care.", "Improving treatment of late life depression in primary care: a randomized clinical trial." ]	[ "The purpose of this study was to evaluate the effectiveness of an activating intervention designed to reduce sick leave duration in patients with emotional distress or minor mental disorders.\n In a 1.5-year randomized controlled trial, 194 patients with minor mental disorders received either an experimental intervention by social workers or general practitioners' usual care. The intervention focused on understanding causes, developing and implementing problem-solving strategies and promoting early work resumption. Outcome measures were sick leave duration, mental health and physical health (questionnaires included the Hospital Anxiety and Depression Scale, the Four-Dimensional Symptom Questionnaire and SF-36), all measured at baseline at and 3, 6 and 18 months later. Multilevel analyses were used to evaluate differences between groups.\n The groups did not differ significantly on any of the outcome measures, except that the experimental group reported higher satisfaction with treatment.\n Although the intervention has benefits, it was not successful at its primary goal (i.e., to reduce sick leave duration in patients with emotional distress or minor mental disorders). Programs aimed at the reduction of sick leave duration may yield better results if targeted at patients with more severe emotional problems than at those with exclusively emotional distress or minor mental disorders, or if delivered by caregivers who are closer to the work environment than are social workers, such as occupational physicians.", "Mental health problems often affect functioning to such an extent that they result in sick leave. The worldwide reported prevalence of mental health problems in the working population is 10%-18%. In developed countries, mental health problems are one of the main grounds for receiving disability benefits. In up to 90% of cases the cause is stress-related, and health-care utilisation is mainly restricted to primary care. The aim of this study was to assess the effectiveness of our Minimal Intervention for Stress-related mental disorders with Sick leave (MISS) in primary care, which is intended to reduce sick leave and prevent chronicity of symptoms.\n Cluster-randomised controlled educational trial.\n Primary health-care practices in the Amsterdam area, The Netherlands.\n A total of 433 patients (MISS n = 227, usual care [UC] n = 206) with sick leave and self-reported elevated level of distress.\n Forty-six primary care physicians were randomised to either receive training in the MISS or to provide UC. Eligible patients were screened by mail.\n The primary outcome measure was duration of sick leave until lasting full return to work. The secondary outcomes were levels of self-reported distress, depression, anxiety, and somatisation.\n No superior effect of the MISS was found on duration of sick leave (hazard ratio 1.06, 95% confidence interval 0.87-1.29) nor on severity of self-reported symptoms.\n We found no evidence that the MISS is more effective than UC in our study sample of distressed patients. Continuing research should focus on the potential beneficial effects of the MISS; we need to investigate which elements of the intervention might be useful and which elements should be adjusted to make the MISS effective.", "Evidence-based practices designed for large urban clinics are not necessarily portable into smaller isolated clinics. Implementing practice-based collaborative care for depression in smaller primary care clinics presents unique challenges because it is often not feasible to employ on-site psychiatrists.\n The purpose of the Telemedicine Enhanced Antidepressant Management (TEAM) study was to evaluate a telemedicine-based collaborative care model adapted for small clinics without on-site psychiatrists.\n Matched sites were randomized to the intervention or usual care.\n Small VA Community-based outpatient clinics with no on-site psychiatrists, but access to telepsychiatrists. In 2003-2004, 395 primary care patients with PHQ9 depression severity scores > or = 12 were enrolled, and followed for 12 months. Patients with serious mental illness and current substance dependence were excluded.\n Medication adherence, treatment response, remission, health status, health-related quality of life, and treatment satisfaction.\n The sample comprised mostly elderly, white, males with substantial physical and behavioral health comorbidity. At baseline, subjects had moderate depression severity (Hopkins Symptom Checklist, SCL-20 = 1.8), 3.7 prior depression episodes, and 67% had received prior depression treatment. Multivariate analyses indicated that intervention patients were more likely to be adherent at both 6 (odds ratio [OR] = 2.1, p = .04) and 12 months (OR = 2.7, p = .01). Intervention patients were more likely to respond by 6 months (OR = 2.0, p = .02), and remit by 12 months (OR = 2.4, p = .02). Intervention patients reported larger gains in mental health status and health-related quality of life, and reported higher satisfaction.\n Collaborative care can be successfully adapted for primary care clinics without on-site psychiatrists using telemedicine technologies.", "To test whether an intervention to improve primary care depression management significantly improves productivity at work and absenteeism over 2 years.\n Twelve community primary care practices recruiting depressed primary care patients identified in a previsit screening.\n Practices were stratified by depression treatment patterns before randomization to enhanced or usual care. After delivering brief training, enhanced care clinicians provided improved depression management over 24 months. The research team evaluated productivity and absenteeism at baseline, 6, 12, 18, and 24 months in 326 patients who reported full-or part-time work at one or more completed waves.\n Employed patients in the enhanced care condition reported 6.1% greater productivity and 22.8% less absenteeism over 2 years. Consistent with its impact on depression severity and emotional role functioning, intervention effects were more observable in consistently employed subjects where the intervention improved productivity by 8.2% over 2 years at an estimated annual value of US 1982 dollars per depressed full-time equivalent and reduced absenteeism by 28.4% or 12.3 days over 2 years at an estimated annual value of US 619 dollars per depressed full-time equivalent.\n This trial, which is the first to our knowledge to demonstrate that improving the quality of care for any chronic disease has positive consequences for productivity and absenteeism, encourages formal cost-benefit research to assess the potential return-on-investment employers of stable workforces can realize from using their purchasing power to encourage better depression treatment for their employees.", "To examine the effectiveness of integrating generalist and specialist care for veterans with depression.\n We conducted a randomized trial of patients screening positive for depression at two Veterans Affairs Medical Center general medicine clinic firms. Control firm physicians were notified prior to the encounter when eligible patients had PRIME-MD depression diagnoses. In the intervention firm, a mental health clinical nurse specialist (CNS) was to: design a treatment plan; implement that plan with the primary care physician; and monitor patients via telephone or visits at two weeks, one month and two months. Primary outcomes (depressive symptoms, patient satisfaction with health care) were collected at 3 and 12 months.\n Of 268 randomized patients, 246 (92%) and 222 (83%) completed 3- and 12-month follow-up interviews. There were no between-group differences in depressive symptoms or satisfaction at 3 or 12 months. The intervention group had greater chart documentation of depression at baseline (63% versus 33%, p = 0.003) and a higher referral rate to mental health services at 3 months (27% versus 9%, p = 0.019). There was no difference in the rate of new prescriptions for, or adequate dosing of, anti-depressant medications. In 40% of patients, CNSs disagreed with the PRIME-MD depression diagnosis, and their rates of watchful waiting were correspondingly high.\n Implementing an integrated care model did not occur as intended. Experienced CNSs often did not see the need for treatment in many primary care patients identified by the PRIME-MD. Integrating integrated care models in actual practice may prove challenging.", "To measure the outcomes of a health assessment, conducted by a nurse, of people aged 75 years and older (75+HA) living independently in their own homes.\n Randomised controlled trial (RCT).\n A convenience sample of six general practices within the Adelaide Western Division of General Practice (AWDGP). A random sample of 100 participants was drawn from practice age-sex registers. Data were collected in initial visits between 1 August 1998 and February 1999, then in follow-up visits one year later.\n Participants were aged 75 years and over on 1 August 1998 and living independently in the community. 145 eligible patients were invited to join the study, and 100 of these consented to enrol (69%).\n A 75+HA conducted in the participant's home by a nurse and reported to their usual general practitioner.\n Primary: number of problems in each group; number of participants with problems; and mortality. Secondary: physical function; psychological (including cognitive) function; falls; and admission to institution.\n There were no significant differences between the control and intervention groups at follow-up in the number of problems, the number of participants with problems, or mortality. In the intervention group, there was significant improvement in self-rated health, geriatric depression score (GDS 15), and number of falls.\n This RCT has not demonstrated improvement in health status of the intervention group which received a 75+HA compared with a control group left to usual care.", "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.", "The object of the study was to evaluate outcomes of a randomized clinical trial (RCT) of a pharmacist intervention for depressed patients in primary care (PC). We report antidepressant (AD) use and depression severity outcomes at 6-months. The RCT was conducted between 1998 and 2000 in 9 eastern Massachusetts PC practices. We studied 533 patients with major depression and/or dysthymia as determined by a screening test done at the time of a routine PC office visit. The majority of participants had recurrent depressive episodes (63.5% with >/=4 lifetime episodes), and 49.5% were taking AD medications at enrollment. Consultation in person and by telephone was performed by a clinical pharmacist who assisted the primary care practitioner (PCP) and patient in medication choice, dose, and regimen, in accordance with AHCPR depression guidelines. Six-month AD use rates for intervention patients exceeded controls (57.5% vs. 46.2%, P =.03). Furthermore, the intervention was effective in improving AD use rates for patients not on ADs at enrollment (32.3% vs. 10.9%, P =.001). The pharmacist intervention proved equally effective in subgroups traditionally considered difficult to treat: those with chronic depression and dysthymia. Patients taking ADs had better modified Beck Depression Inventory (mBDI) outcomes than patients not taking ADs, (-6.3 points change, vs. -2.8, P =.01) but the outcome differences between intervention and control patients were not statistically significant (17.7 BDI points vs. 19.4 BDI points, P =.16). Pharmacists significantly improved rates of AD use in PC patients, especially for those not on ADs at enrollment, but outcome differences were too small to be statistically significant. Difficult-to-treat subgroups may benefit from pharmacists' care.", "This research study evaluates the effectiveness of a multifaceted intervention program to improve the management of depression in primary care.\n One hundred fifty-three primary care patients with current depression were entered into a randomized controlled trial. Intervention patients received a structured depression treatment program in the primary care setting that included both behavioral treatment to increase use of adaptive coping strategies and counseling to improve medication adherence. Control patients received \"usual\" care by their primary care physicians. Outcome measures included adherence to antidepressant medication, satisfaction with care of depression and with antidepressant treatment, and reduction of depressive symptoms over time.\n At 4-month follow-up, significantly more intervention patients with major and minor depression than usual care patients adhered to antidepressant medication and rated the quality of care they received for depression as good to excellent. Intervention patients with major depression demonstrated a significantly greater decrease in depression severity over time compared with usual care patients on all 4 outcome analyses. Intervention patients with minor depression were found to have a significant decrease over time in depression severity on only 1 of 4 study outcome analyses compared with usual care patients.\n A multifaceted primary care intervention improved adherence to antidepressant regimens and satisfaction with care in patients with major and minor depression. The intervention consistently resulted in more favorable depression outcomes among patients with major depression, while outcome effects were ambiguous among patients with minor depression.", "Facilitate primary care physicians' compliance with recommended standards of care for late life depression by reducing barriers to recognition and treatment.\n Randomized controlled clinical trial of physician-targeted interventions.\n Academic primary care group practice caring for an urban, medically indigent patient population.\n Patients aged 60 and older who exceeded the threshold on the Centers for Epidemiologic Studies Depression Scale (CES-D) and the Hamilton Depression Rating Scale (HAM-D) and their primary care physicians.\n Physicians of intervention patients were provided with patient-specific treatment recommendations during 3 special visits scheduled specifically to address the patient's symptoms of depression. In general, physicians were encouraged to establish a diagnosis of depression and educate their patient about the diagnosis, discontinue medications that can cause or exacerbate depressive symptoms, initiate antidepressants when appropriate, and consider referral to psychiatry. Guidelines for prescribing antidepressants were provided. Control physicians received no intervention, and control patients received usual care.\n Frequency of recording a depression diagnosis, stopping medications associated with depression, initiating antidepressant medication, and psychiatry referral; mean changes in HAM-D and Sickness Impact Profile (SIP) scores.\n One hundred three physicians and 175 patients were involved in the clinical trial. Physicians of intervention patients were more likely to diagnose depression and prescribe antidepressants (P < 0.01). There were no differences between the groups in the frequency of stopping medications associated with depression or referrals to psychiatry. Medications with the strongest cause and effect relationship to depression were infrequently used in this cohort of patients. Although both groups showed improvement in HAM-D and SIP scores, we were unable to demonstrate significant differences in HAM-D or SIP scores between the 2 groups.\n Intensive screening and feedback of patient-specific treatment recommendations increased the recognition and treatment of late life depression by primary care physicians. However, we were unable to demonstrate significant improvement in depression or disability severity among intervention patients despite the informational support provided to their physicians. Efforts to improve the functional status of these patients may require more integrated interventions and more aggressive attempts to target psychosocial stressors traditionally outside the purview of primary care." ]	Based on a heterogeneous sample of studies, there is currently no evidence of an effect of medication alone, enhanced primary care, psychological interventions or the combination of those with medication on sickness absence of depressed workers. In future RCTs, interventions should specifically address work issues, and occupational outcomes should be used to measure the effect..
CD010067	[ "20599311", "12188468", "18237352" ]	[ "Improved health outcomes in urban slums through infrastructure upgrading.", "Impact of improvement of water supply on household economy in a squatter area of Manila.", "Strategies for improving the quality of health care in maternal and child health in low- and middle-income countries: an overview of systematic reviews." ]	[ "The world is rapidly urbanizing with over half the population now living in urban areas. As the urban population grows, so does the proportion of these persons living in slums where conditions are deplorable. These conditions concentrate health hazards leading to higher rates of morbidity and mortality. This growing problem creates a unique challenge for policymakers and public health practitioners. While the Millennium Development Goals (MDGs) aim to address these conditions and standards for water and sanitation as well as pertinent health outcomes, little evidence on interventions exists to guide policymakers. Upgrades in slum household water and sanitation systems have not yet been rigorously evaluated to demonstrate whether there is a direct link to improved health outcomes. This study aims to show that slum upgrading as carried out in Ahmedabad, India, led to a significant decline in waterborne illness incidence. We employ a quasi-experimental regression model using health insurance claims (for 2001-2008) as a proxy for passive surveillance of disease incidence. We found that slum upgrading reduced a claimant's likelihood of claiming for waterborne illness from 32% to 14% and from 25% to 10% excluding mosquito-related illnesses. This study shows that upgrades in slum household infrastructure can lead to improved health outcomes and help achieve the MDGs. It also provides guidance on how upgrading in this context using microfinance and a public-private partnership can provide an avenue to affect positive change.\n Copyright (c) 2010 Elsevier Ltd. All rights reserved.", "To estimate the impact of the improvement of water supply. a comparative study on water collection and household expenditure on water was conducted between a former squatter community with an improved water supply (Leveriza: LE) and a typical squatter community with public water faucets (Maestranza: MA) in Manila, the Philippines. Data were collected from 201 structured household interviews and a focus group discussion among housewives in each community. To measure the time spent collecting water, observations of private and public water faucets were conducted. The residents in LE enjoyed significantly larger quantities of water from private water connections than in MA, where only three public water faucets were available as a water source. Conversely, the unit price of water in LE was much lower than in MA. In LE, 72.1% of the households started working for more income using time saved through the improvement of water supply and the proportion of the households under the poverty threshold was reduced from 55.6% to 29.9%. In MA, 68.6% of the households expressed their willingness to work for more income when time spent collecting water was saved. It would be possible for MA to reduce the proportion of the households under the poverty threshold through the improvement of the water supply. The results of the study indicated that the improvement of water supply would possibly encourage urban slum residents to increase their household incomes through reallocating time saved to income-generating activities. The underserved residents spent more money for less water compared to those with access to private water connections. In MA, it took 3-4 h, on average, to complete one water collecting task, even though the nearest public water faucet was within 100 m of any housing unit. This suggests that the definition of accessibility to safe water be reconsidered when discussing the urban poor.", "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." ]	A high risk of bias within the included studies, heterogeneity and evidence gaps prevent firm conclusions on the effect of slum upgrading strategies on health and socio-economic wellbeing. The most common health and socio-economic outcomes reported were communicable diseases and indicators of financial poverty. There was a limited but consistent body of evidence to suggest that slum upgrading may reduce the incidence of diarrhoeal diseases and water-related expenditure. The information available on slum dwellers’ perspectives provided some insight to barriers and facilitators for successful implementation and maintenance of interventions. The availability and use of reliable, comparable outcome measures to determine the effect of slum upgrading on health, quality of life and socio-economic wellbeing would make a useful contribution to new research in this important area. Given the complexity in delivering slum upgrading, evaluations should look to incorporate process and qualitative information alongside quantitative effectiveness data to determine which particular interventions work (or don’t work) and for whom.
CD009517	[ "19568761", "20607003", "12042269" ]	[ "Local injury to the endometrium on the day of oocyte retrieval has a negative impact on implantation in assisted reproductive cycles: a randomized controlled trial.", "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.", "A prospective randomized study: day 2 versus day 5 embryo transfer." ]	[ "To evaluate the effect of local injury to the endometrium on the day of oocyte retrieval on implantation and pregnancy rates in assisted reproductive cycles.\n In a prospective controlled trial, a total of 156 patients, <38 years old, in their first in vitro fertilization (IVF) cycle were randomized. In 77 patients, two small endometrial samples from anterior and posterior walls of uterus were obtained with a Novak curette on the day of oocyte retrieval and in 79 patients no intervention was performed.\n The experimental and control patients were matched regarding women's age, body mass index, basal FSH, duration and etiology of infertility, treatment protocol, number of retrieved oocyte, endometrial thickness, percentage of intracytoplasmic sperm injection performance, fertilization rate, the percentage of patients with good and top quality embryos, and the number of embryos transferred. The implantation rate (7.9 vs. 22.9%), clinical (12.3 vs. 32.9%; odds ratio = 0.25; 95% confidence interval = 0.12-0.66; p < 0.05) and ongoing pregnancy (9.6 vs. 29.1%; odds ratio = 0.25; 95% confidence interval = 0.10-0.64; p < 0.05) rates were significantly lower in experimental group, compared with 79 controls.\n According to the results of this study, local injury to the endometrium on the day of oocyte retrieval disrupts the receptive endometrium and has a negative impact on implantation and IVF outcomes.", "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.", "This randomized controlled study was performed in an unselected IVF/ICSI population to test the hypothesis that blastocyst transfers result in higher clinical pregnancy rates (CPR) per oocyte retrieval when compared with day 2 transfers.\n Blind randomization for transfer on day 2 (group 1) or day 5/6 (group 2) was performed before stimulation. Oocytes and embryos were cultured in sequential media in 5.5% CO(2), 5% O(2), 89.5% N(2) and 90% humidity. A maximum of two embryos was transferred.\n The two groups were similar for age, IVF indication, number of treatment cycles, rate of ICSI/IVF, number of fertilized oocytes and number of embryos transferred. The CPR/oocyte retrieval was comparable in group 1 (32%) and in group 2 (44%), while the CPR/embryo transfer was significantly higher (P < 0.01) in group 2 (60%) than in group 1 (35%). Similarly, the implantation rate per embryo transferred was significantly higher (P < 0.03) in group 2 (46%) than in group 1 (29%). The cryo-augmented delivery rate/oocyte retrieval was comparable in group 2 (36.3%) and in group 1 (28.6%).\n This randomized study in an unselected population showed a significantly higher CPR/embryo transfer and a tendency toward a higher CPR/oocyte retrieval in patients receiving blastocysts when compared with day 2 transfers." ]	Endometrial injury performed prior to the embryo transfer cycle improves clinical pregnancy and live birth rates in women undergoing ART. It is advisable not to perform endometrial injury on the day of oocyte retrieval because it appears to significantly reduce clinical and ongoing pregnancy rates. There is insufficient evidence regarding the effect of endometrial injury on multiple pregnancy or miscarriage and none on adverse events such as pain and bleeding.
CD003987	[ "18161401", "8605778", "16485589", "15608030", "11849631", "16904415", "19442776", "7775629", "15697102", "11672550", "22078632", "16723306", "11576570", "18580398", "9141548", "19838585", "7040192", "16199429", "22067763", "21669426", "20654754", "19766950", "3310826", "9098463", "3781003", "22678035", "2867858", "2335101", "11102587", "8403908", "19501213", "1451519", "12499033", "16171729", "22066891", "15302293", "6241559", "2107056", "17963858", "1764941", "16763008", "15576394" ]	[ "Effects of low-dose oral contraceptives on body weight: results of a randomized study of up to 13 cycles of use.", "A comparative study of one-year weight gain among users of medroxyprogesterone acetate, levonorgestrel implants, and oral contraceptives.", "Weight changes in clients on hormonal contraceptives in Zaria, Nigeria.", "Effects of two types of hormonal contraception--oral versus intravaginal--on the sexual life of women and their partners.", "Contraceptive efficacy and cycle control with the Ortho Evra/Evra transdermal system: the analysis of pooled data.", "Comparison profiles of cycle control, side effects and sexual satisfaction of three hormonal contraceptives.", "Association between efficacy and body weight or body mass index for two low-dose oral contraceptives.", "Effects of a new oral contraceptive containing an antimineralocorticoid progestogen, drospirenone, on the renin-aldosterone system, body weight, blood pressure, glucose tolerance, and lipid metabolism.", "A comparative study on the effects of a contraceptive vaginal ring NuvaRing and an oral contraceptive on carbohydrate metabolism and adrenal and thyroid function.", "Weight change and adverse event incidence with a low-dose oral contraceptive: two randomized, placebo-controlled trials.", "The effect of obesity and low-dose oral contraceptives on carbohydrate and lipid metabolism.", "Contraception in perimenopausal women with diabetes mellitus.", "A prospective, controlled study of the effects of hormonal contraception on bone mineral density.", "Effect of oral contraceptives on weight and body composition in young female runners.", "Effect of postmenopausal hormone therapy on body weight and waist and hip girths. Postmenopausal Estrogen-Progestin Interventions Study Investigators.", "[Variation of weigth among users of the contraceptive with depot-medroxyprogesterone acetate according to body mass index in a six-year follow-up].", "Oral contraception in diabetic women. A cross-over study on serum and high density lipoprotein (HDL) lipids and diabetes control during progestogen and combined estrogen/progestogen contraception.", "Combined lifestyle modification and metformin in obese patients with polycystic ovary syndrome. A randomized, placebo-controlled, double-blind multicentre study.", "Body weight does not impact pregnancy rates during use of a low-dose extended-regimen 91-day oral contraceptive.", "Combined contraceptive ring versus combined oral contraceptive (30-μg ethinylestradiol and 3-mg drospirenone).", "Effect of oral contraceptive containing ethinyl estradiol combined with drospirenone vs. desogestrel on clinical and biochemical parameters in patients with polycystic ovary syndrome.", "A longitudinal comparison of body composition changes in adolescent girls receiving hormonal contraception.", "Blood glucose, serum insulin, serum growth hormone and serum glycosylated proteins during two years' oral contraception with low-estrogen combinations.", "Evaluation of body composition during low-dose estrogen oral contraceptives treatment.", "Oral contraceptives in diabetic women: metabolic effects of four compounds with different estrogen/progestogen profiles.", "Contraceptive failure rates of etonogestrel subdermal implants in overweight and obese women.", "A randomized double-blind study of the effects of two low-dose combined oral contraceptives on biochemical aspects. Report from a seven-centred study. WHO Special Programme of Research, Development and Research Training in Human Reproduction. Task force on Oral Contraceptives.", "Comparison of two triphasic contraceptives with different progestogens: effects on metabolism and coagulation proteins.", "Depo-provera associated with weight gain in Navajo women.", "A comparative study of two low-dose combined oral contraceptives: results from a multicenter trial.", "Route of administration of contraceptives containing desogestrel/etonorgestrel and insulin sensitivity: a prospective randomized study.", "Lipid and biochemical changes after low-dose oral contraception.", "Randomized controlled study of the influence of two low estrogen dose oral contraceptives containing gestodene or desogestrel on carbohydrate metabolism.", "Adolescent use of the monthly contraceptive injection.", "Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17β-oestradiol compared with one containing levonorgestrel and ethinylestradiol on haemostasis, lipids and carbohydrate metabolism.", "A randomized, 48-week, placebo-controlled trial of intensive lifestyle modification and/or metformin therapy in overweight women with polycystic ovary syndrome: a pilot study.", "Effects of hormonal contraceptives on milk volume and infant growth. WHO Special Programme of Research, Development and Research Training in Human Reproduction Task force on oral contraceptives.", "Microdose intravaginal levonorgestrel contraception: a multicentre clinical trial. III. The relationship between pregnancy rate and body weight. World Health Organization. Task Force on Long-Acting Systemic Agents for Fertility Regulation.", "Contraceptive vaginal ring use for women has less adverse metabolic effects than an oral contraceptive.", "Progestagen-only oral contraceptives: comparison of the metabolic effects of levonorgestrel and norethisterone.", "Effects on cycle control and bodyweight of the combined contraceptive ring, NuvaRing, versus an oral contraceptive containing 30 microg ethinyl estradiol and 3 mg drospirenone.", "The effect of combination therapy with metformin and combined oral contraceptives (COC) versus COC alone on insulin sensitivity, hyperandrogenaemia, SHBG and lipids in PCOS patients." ]	[ "To compare the effect of 2 oral contraceptives (OCs) on body weight.\n A randomized, parallel-group, multicenter study of 1,723 women taking an OC with norgestimate (NGM) 180/215/250 microg/ethinyl estradiol (EE) 25 microg vs. 1,171 women taking on OC with norethindrone acetate 1 mg/EE 20 microg for 6-13 cycles was performed. Body weight changes between baseline and cycle 6 and baseline and cycle 13 were analyzed. Analysis included not only changes in mean body weight but also the distribution of changes that were within 5% of baseline weight, 5-10% of baseline weight and > 10% of baseline weight. Only the 10% change was felt to be clinically significant.\n The distribution of body weight changes did not statistically differ between the 2 OC groups for any parameter measured. The mean weight change after 6 months for the NGM/EE and norethindrone acetate/EE groups was +0.71 kg and +0.57 kg, respectively. At 13 cycles for the NGM/EE and norethindrone acetate/ EE groups, the mean body weight change was +0.93 kg and +0.62 kg, respectively. Only 0.3% of subjects in both OC groups experienced a 10% change in weight.\n Use of OCs does not substantially affect body weight for most women.", "With the recent introduction and growing popularity of Depo-Provera Contraceptive Injection, concern about the potential for weight gain during treatment has been raised. The purpose of the present study was to determine whether or not Depo-Provera Contraceptive Injection is associated with greater weight gain, and incidence thereof, than Norplant implants or oral contraceptives. A retrospective chart review of patients seen at a state- and federally-funded clinic was conducted. Fifty women in each treatment group who met the study criteria were identified and included in the study evaluation. Mean one-year weight gain for subjects in each group was as follows: -2.0 pounds in the oral contraceptive group, -1.8 pounds in the Norplant implants group, and +0.1 pounds in the Depo-Provera Contraceptive Injection group. While results among treatment groups differed slightly, no significant weight change occurred in any of the treatment groups.", "Misconceptions exist in Nigeria about the effects of hormonal contraceptives on weight, which may have negative effects on contraceptive use. Data from case notes of clients attending the reproductive health centre at the Ahmadu Bello University Teaching Hospital, Zaria, between 1993 and 1995, were analysed to determine the effects of hormonal contraceptives on body weight, comparing them to clients using intrauterine contraceptive devices. Weight changes were not significantly different in clients using hormonal contraceptives and those using intrauterine contraceptive devices. This information will be beneficial in contraceptive counselling for clients in this environment and provide a baseline for further research.", "Data relating to the influence of hormonal contraception on sexual life are conflicting and mostly they refer to oral contraceptives. In this randomized, controlled, prospective study we compared the effect of an intravaginal hormonal contraceptive with the effect of a combined oral contraceptive on sexual function.\n Fifty-one healthy women with a permanent partner and an active sexual life were randomly divided in two groups according to a computer-generated randomization list: 26 women (group A) used an intravaginal contraceptive releasing 120 microg/day of etonogestrel and 15 microg/day of ethinylestradiol (EE) and 25 women (group B) used an oral contraceptive containing 20 microg di EE and 150 microg of desogestrel. Twenty-five women participated in the study as control group (group C). A specific questionnaire was completed by the patients and their partners at the start of the study and after cycles 3 and 6 of contraceptive use.\n Within 3 months of contraceptive use, women from both groups A and B reported a global improvement in sexual function. A statistically significant increase in sexual fantasy was reported only by patients of group A. Whereas partners of the women in both groups A and B reported an improvement in sexual function after 3 months of contraceptive intake, only patients' partners of group A reported a significant increase in sexual interest, complicity and sexual fantasy.\n Both hormonal contraceptives tested were seen to have a positive effect on some aspects of sexual function. The intravaginal contraceptive ring seems to exert a further positive effect on the psychological aspect of both women and their partners, which is evident from an improved complicity and sexual satisfaction.", "To present efficacy and cycle control data pooled from three pivotal studies of the contraceptive patch (Ortho Evra/Evra).\n Three multicenter, open-label, contraceptive studies that included up to 13 treatment cycles.Setting: 183 centers.\n 3,319 women.Intervention(s): Three consecutive 7-day patches (21 days) with 1 patch-free week per cycle.\n Contraceptive efficacy and cycle control.\n Overall and method failure life-table estimates of contraceptive failure through 13 cycles were 0.8% (95% CI, 0.3%-1.3%) and 0.6% (95% CI, 0.2%-0.9%), respectively. Corresponding Pearl indices were 0.88 (95% CI, 0.44-1.33) and 0.7 (95% CI, 0.31-1.10). Contraceptive failure among women with a body weight < 90 kg (<198 lb) was low and uniformly distributed across the weight range. A subgroup of women with body weight > or = 90 kg (> or = 198 lb) may have increased risk of pregnancy. The incidence of breakthrough bleeding was low and decreased over time.\n In contraceptive patch users, the overall annual probability of pregnancy was 0.8% and the method failure probability was 0.6%. The efficacy of the patch was high and similar across age and racial groups. Among women < 90 kg (<198 lb), contraceptive failure was low and uniformly distributed across the range of body weights. In women > or = 90 kg (> or = 198 lb), contraceptive failures may be increased. Efficacy and cycle control have been shown to be comparable to an established oral contraceptive.", "The objective of this study was to compare cycle control, tolerability and sexual well-being with the use of three hormonal contraceptives.\n In this prospective randomized study, the effects of two combined oral contraceptives [20 microg of ethinylestradiol (EE)/100 microg of levonorgestrel and 15 microg of EE/60 microg of gestodene] were compared with those of the vaginal ring (15 microg of EE/120 microg of etonogestrel). One-year data from 280 women were obtained. We investigated the pattern of menstrual cycle and the incidence of weight gain, nausea, headache, breast tenderness, irritability, depression and vaginal dryness. Moreover, desire and sexual satisfaction were evaluated. Finally, the cumulative rate of discontinuation in the three groups was estimated.\n The analysis of adverse events revealed two crucial points for acceptability, compliance and continuation: poor cycle control and disturbance of sexual intercourse due to vaginal dryness and loss of desire.", "This analysis investigated the association of oral contraceptive efficacy with body weight and body mass index (BMI) for hypothesis-generating purposes.\n Data were from a randomized, parallel-group trial of 180/215/250 mcg of norgestimate (NGM)/25 mcg of ethinyl estradiol (EE) (given to 1671 women) and 1 mg of norethindrone acetate (NETA)/20 mcg of EE (given to 1139 women). Pregnancies were evaluated across BMI deciles and by BMI and body weight dichotomies. A Pearl index was calculated for each treatment group. The relative risk (RR) of pregnancy was calculated with a Cox proportional hazards model.\n The Pearl index for women who received NGM/EE was 2.36 [95% confidence interval (CI)=1.33-3.40]; for those who received NETA/EE, the Pearl index was 3.29 (95% CI=1.81-4.77). Consistent, weak positive associations between weight and pregnancy risk were found. Overall, for women with a BMI >or=25 kg/m(2) (compared with women with a BMI <25 kg/m(2)), the RR of pregnancy was 1.84 (95% CI=0.98-3.45); that for women who received NGM/EE was 1.39 (95% CI=0.57-3.40), whereas that for women who received NETA/EE was 2.49 (95% CI=1.01-6.13). For women with a body weight >or=70 kg (compared with women with a body weight <70 kg), the RR was 1.25 (95% CI=0.63-2.46); that for women who received NGM/EE was 1.41 (95% CI=0.56-3.54), whereas that for women who received NETA/EE was 1.12 (95% CI=0.40-3.12).\n Women in the higher body weight or BMI category showed a small increase in the risk of pregnancy with these oral contraceptives, but this increase was not statistically significant overall or for either formulation studied.", "Combined hormonal oral contraceptives (OCs) may lead to a mild rise in blood pressure and body weight. In rare instances, large increments in blood pressure are measured. We investigated the effect of a combination of ethinyl estradiol (EE) plus a progestogen with antimineralocorticoid, i.e. natriuretic, properties [Drospirenone (DRSP)] on body weight, blood pressure, the renin-aldosterone system, atrial natriuretic factor, plasma lipids, and glucose tolerance. It is anticipated that this will lead to the development of an OC that does not raise body weight or blood pressure. Four groups of 20 women each received 30 micrograms EE plus 3 mg DRSP (group A), 20 micrograms EE plus 3 mg DRSP (group B), 15 micrograms EE plus 3 mg DRSP (group C), and, as a control OC, 30 micrograms EE plus 150 micrograms levonorgestrel (Microgynon, Schering; group D) for 6 months. During the OC-free control cycles before and after treatment and throughout treatment, the target parameters were measured. Between the pretreatment cycle and the sixth treatment cycle, mean body weight fell by 0.8 to 1.7 kg in groups A, B, and C (P < 0.05 vs. D), whereas it rose by 0.7 kg in group D. Systolic and diastolic blood pressures fell by 1-4 mm Hg in groups A, B, and C (significant for A and C vs. D) and increased by 1-2 mm Hg in group D. Renin substrate rose equally in all groups (P < 0.05), whereas PRA and plasma aldosterone rose significantly only in the DRSP groups, presumably due to sodium loss. In the DRSP groups, high density lipoprotein cholesterol rose (P < 0.05), in contrast to group D. Low density lipoprotein cholesterol fell slightly (P > 0.05), whereas triglyceride levels showed a stronger increase in the DRSP groups (P < 0.05) than in group D. All groups attained good cycle control; group A had the best. Side-effects were minimal. To our knowledge, this is the first report on a combined OC that leads to a small decrease in body weight and blood pressure. It may be especially beneficial for women susceptible for a gain in weight and a rise in blood pressure.", "To compare carbohydrate metabolism, adrenal and thyroid function during use of a combined contraceptive vaginal ring (NuvaRing, NV Organon, Oss, The Netherlands) with those of a combined oral contraceptive.\n Healthy women aged 18-40 years used either the vaginal ring, delivering 15 microg ethinylestradiol and 120 microg of etonogestrel per day, or a combined oral contraceptive containing 30 microg ethinylestradiol and 150 microg levonorgestrel, for six cycles. Each cycle comprised 3 weeks of use of the ring or the pill followed by 1 ring- or pill-free week. The following parameters were measured at baseline and at the end of cycles 3 and 6: carbohydrate metabolism (glucose, insulin, glycosylated hemoglobin); adrenal function (total cortisol, cortisol binding globulin, dehydroepiandrosterone sulfate); thyroid function (thyroid stimulating hormone, free thyroxine).\n Small and similar increases in insulin were seen in both groups. Concentrations of cortisol binding globulin and total cortisol rose significantly less during ring use than during combined oral contraceptive use (cycle 3, p= 0.0002; cycle 6, p < 0.0001). Levels of dehydroepiandrosterone sulfate did not change in either group. Thyroid stimulating hormone levels increased significantly more in the ring group at cycle 3 (p = 0.0016) but free thyroxine levels were unchanged in both groups.\n Both the vaginal ring and the oral contraceptive have no clinically relevant effects on carbohydrate metabolism, adrenal or thyroid function.", "Changes in body weight and the incidence of estrogen-related side effects with low-dose oral contraceptives (OCs) containing 20 microg ethinyl estradiol (EE) have not been demonstrated in placebo-controlled trials. Two placebo-controlled, randomized trials demonstrated the efficacy of a low-dose OC for the treatment of acne in healthy females (n = 704; >or=14 years old) with regular menstrual cycles and moderate facial acne. Patients were randomized to receive 20 microg EE/100 microg levonorgestrel (LNG) or placebo for six cycles. Body weight was measured at baseline and during Cycles 1, 3, and 6. The occurrence of adverse events was recorded at each visit. Mean changes in weight from baseline were similar with 20 microg EE/100 microg LNG [0.72 kg +/- 2.64 (SD; n = 349)] and placebo [0.56 kg +/- 2.64 (SD; n = 355; p > 0.05)] for the last measured weight of each patient. Rates of headache, nausea, weight gain, and breast pain, side effects commonly attributed to OCs, were also similar between groups (p > 0.05). No serious, unexpected, drug-related adverse events occurred during the study. The low-dose OC containing 20 microg EE/100 microg LNG is safe, well tolerated, and does not cause weight gain.", "Combination oral contraceptives (OCs) have little effect on carbohydrate and lipid metabolism in normal-weight women. Based on lack of change in intermediate markers, as well as results of epidemiologic studies, low-dose OCs do not increase the risk of diabetes or cardiovascular disease. Obesity is a risk factor for impaired glucose tolerance, diabetes and coronary artery disease, and most previous OC studies excluded these women; thus, we have limited information about carbohydrate and lipid metabolism in obese OC users.\n This study compared changes in carbohydrate and lipid parameters in 71 normal-weight and 38 obese women initiating the OC. Women were randomized to two pills: 30 mcg ethinyl estradiol (EE)/150 mcg levonorgestrel (LNG) or 20 mcg EE/100 mcg LNG. Participants underwent baseline and cycle-3 measurements of fasting serum glucose; insulin; triglycerides and total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol.\n Normal-weight and obese participants experienced similar changes in mean glucose, insulin and log homeostatic model assessment, as well as similar changes in total cholesterol, HDL and triglycerides; however, change in mean LDL (-4.9±20.6 mg/dL vs. +3.8±17.3 mg/dL) was different between the obese and normal-weight groups, respectively. Among the obese participants, change in glucose was marginally greater with the higher dose pill (p=.06); otherwise, changes between the body mass index groups were not modified by pill dose.\n Obesity had little effect on any OC-induced changes in carbohydrate or lipid metabolism except for a borderline adverse interaction between obesity and OC dose with respect to fasting glucose and a positive interaction between obesity and OC use with respect to LDL cholesterol.\n Copyright © 2012 Elsevier Inc. All rights reserved.", "To assess the effect of combined oral contraceptives (COCs) and intrauterine devices (IUDs) on carbohydrate and lipid metabolism and hemostasis in perimenopausal diabetic women.\n The open randomized study included a total of 113 diabetic women using COCs with different estrogen/progestogen profiles - ethinylestradiol (EE) 20 microg/desogestrel 150 microg, EE 30 microg/desogestrel 150 microg and EE 30 microg/gestodene 75 microg - and levonorgestrel-releasing or copper IUDs. Average daily insulin requirements, levels of glycosylated hemoglobin, total cholesterol, triglycerides, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, the state of coagulation hemostatis and fibrinolytic activity were determined at baseline and after 3, 6, 9 and 12 months of contraception. The control group was composed of 40 age-matched diabetic women who did not use any methods of contraception.\n Neither COCs nor IUDs influenced glycosylated hemoglobin and had little or no influence on the elevation in the requirements for insulin preparations. The majority of the preparations did not exert any unfavorable effect on the blood lipid profile. Taking COCs was accompanied by increased intravascular activation of blood platelets and to a lesser degree by alterations in parameters of hemostatic homeostasis. The use of IUDs had a neutral effect on blood coagulation and fibrinolysis systems.\n Comparing lipid levels and hemostatic variables as a function of glycosylated hemoglobin level, we conclude that diabetes control has greater influence on these parameters than the type and dose of steroids involved in the contraceptive devices.", "To compare the effect of depot medroxyprogesterone acetate (DMPA) and two types of oral contraceptives (OC) on bone mineral density (BMD) among women 18-33 years of age with those not using hormonal contraception.\n Data from 155 women were analyzed. Depot medroxyprogesterone acetate was administered to 33 women; 63 women who chose oral contraception were randomly assigned to receive either a norethindrone-containing pill (n = 28) or a desogestrel-containing pill (n = 35). Fifty-nine women who did not use hormonal contraception served as controls. Lumbar spine BMD was determined using dual-energy x-ray absorptiometry at baseline and after 12 months of contraceptive use. We analyzed method-related percent change in BMD while controlling for body mass index, calcium intake, exercise, and smoking. We had approximately 90% power to detect a 2.5% difference between any two groups.\n Users of DMPA experienced a mean BMD loss of 2.74% over 12 months compared with controls who sustained a 0.37% loss (P = .01). Users of OCs generally demonstrated a gain (2.33% for norethindrone-containing pills, 0.33% for desogestrel-containing pills), which was different from controls among users of norethindrone-containing pills (P = .01), but not among users of desogestrel-containing pills (P = .99). Observed changes in BMD among DMPA users differed from women who used either type of pill (P < .002).\n Depot medroxyprogesterone acetate has an adverse effect on BMD, in comparison with OCs or nonhormonal methods, when used for 12 months. Results must be interpreted cautiously until it is determined whether these effects endure or are reversible.", "To examine the effect of oral contraceptives (OC) on body weight, fat mass, percent body fat, and lean mass in young female distance runners.\n The study population consisted of 150 female competitive distance runners aged 18-26 yr who had participated in a 2-yr randomized trial of the effect of the OC Lo/Ovral (30 microg of ethinyl estradiol and 0.3 mg of norgestrel) on bone health. Weight and body composition were measured approximately yearly by balance beam scales and dual-energy x-ray absorptiometry, respectively.\n Women randomized to the OC group tended to gain slightly less weight (adjusted mean difference (AMD) = -0.54 +/- 0.31 kg.yr, P = 0.09) and less fat (AMD = -0.35 +/- 0.25 kg.yr, P = 0.16) than those randomized to the control group. OC assignment was associated with a significant gain in lean mass relative to controls among eumenorrheic women (those who had 10 or more menstrual cycles in the year before baseline; AMD = 0.77 +/- 0.17 kg.yr, P < 0.0001) but not among women with fewer than 10 menstrual cycles in that year (AMD = 0.02 +/- 0.35 kg.yr, P = 0.96). Treatment-received analyses yielded similar results.\n This randomized trial confirms previous findings that OC use does not cause weight or fat mass gain, at least among young female runners. Our finding that this OC is associated with lean mass gain in eumenorrheic runners, but not in those with irregular menses, warrants examination in other studies.", "Reports from cross-sectional comparisons, nonrandomized prospective studies, and relatively small clinical trials indicate that postmenopausal hormone therapy may slightly decrease the amount of weight typically gained by women during the decade following menopause. Despite this, widespread belief remains that hormone therapy may cause weight gain. We use data from the Postmenopausal Estrogen/Progestin Interventions trial to characterize the impact of postmenopausal hormone therapy on weight and fat distribution and to examine the consistency of this impact among subgroups of women defined by lifestyle, clinical, and demographic factors. The Postmenopausal Estrogen/Progestin Interventions trial was a 3-yr, placebo-controlled, randomized clinical trial of 875 women assessing the effects on cardiovascular risk factors of four hormone regimens: oral conjugated equine estrogen (CEE) therapy (0.625 mg daily alone), CEE in combination with medroxyprogesterone acetate (2.5 mg daily), CEE in combination with medroxyprogesterone acetate (10 mg daily on days 1-12), and CEE in combination with micronized progesterone (200 mg daily on days 1-12). Women randomly assigned to CEE with or without a progestational agent averaged 1.0 kg less weight gain at the end of 3 yr (P = 0.006) than those assigned to placebo. Assignment to CEE was also associated with averages of 1.2 cm less increase in waist girth (P = 0.01) and 0.3 cm less increase in hip (P = 0.07) girth. In regression models that included weight change as a covariate, none of these differences reached statistical significance. There were no significant differences in weight or girth changes among any of the four active hormone regimens. After accounting for the effects of assignment to active hormone therapy and baseline weight, older age (P 0.008) and higher physical activity level at baseline (P = 0.002) were also independently predictive of less weight gain. The impact of hormone therapy on weight gain was similar among subgroups, except for those defined by baseline smoking status (P = 0.04) and physical activity level at home (P = 0.02). Factors that were independently associated with smaller increases in girths were: for waist, greater overall activity (P = 0.005) and Hispanic ethnicity (P = 0.02); and for hip, work activity (P = 0.003) and greater alcohol consumption (P = 0.03). None of these factors significantly affected the observed overall relationships between estrogen and changes in girth.", "To determine weight variation in women with different Body Mass Index (BMI) in use of trimestral injections of depot-medroxyprogesterone acetate (DMPA), and compare it to women users of a non-hormonal method.\n Retrospective study with the chart review of 226 DMPA users and 603 controls, users of DIU TCu380A. Women were distributed in categories, according to their initial BMI, as having normal weight (<25 kg/m(2)), overweight (25 to 29,9 kg/m(2)) and being obese (>or=30 kg/m(2)), and were followed-up for six years, with yearly measurements of weight and BMI. The statistic test ANOVA was used to measure the weight variation among the groups in each BMI category every year.\n The average age at the onset of the method employed was higher in the study group than in the controls, in all the BMI categories: 31.6+/-SD 7.1 X 27.4+/-SD 5.5 in the normal weight category (p<0.0001); 37.3+/-SD 6.8 X 29.2+/-SD 6.0 in the overweight category (p<0.0001); and 35.3+/-SD 6.4 X 29.7+/-SD 5.8 among obese women (p<0.0001). DMPA users showed weight increase as compared to the controls in the overweight category (p=0.0082); and the weight increase along the observation period was also higher among the DMPA users than among the controls, for the normal weight (p<0.0001) and overweight (p=0.0008) categories. In the obese group, there was no BMI variation between the groups, nor along the period during which they were using the method.\n There was no change in weight gain among DMPA users from the obese category. Prospective studies should be done with metabolic tests to establish the determining factors of weight gain in normal and overweight women.", "Twenty-three young women with insulin-dependent diabetes were randomly allocated to contraceptive treatment with either a progestogen only (Lynestrenol 0.5 mg) (LYN) or a combined oral contraceptive (OC) (ethinyl estradiol 50 micrograms + lynestrenol 2.5 micrograms) (EE + LYN). After six months treatment the medication was withdrawn for at least two months, after which the patients were placed on the other preparation. Diabetes control and serum and high density lipoprotein (HDL) lipids were assessed before and after 1, 3 and 6 months of treatment. Low-dose LYN administration did not alter the insulin requirement, blood glucose or body weight while the combined EE + LYN treatment increased the insulin requirement (p less than 0.01) without altering blood glucose or body weight. Low-dose LYN reduced serum triglycerides (p less than 0.001), serum cholesterol (p less than 0.001) and serum phospholipids (p less than 0.01) without affecting HDL lipids, while EE + LYN gave an inconsistent increase in serum triglycerides (p less than 0.01) but no change in HDL lipids. These findings confirm our earlier results and we conclude that EE + LYN influences diabetes control slightly more (although still not seriously) than the low-dose LYN. It is suggested that insulin-dependent diabetics (in contrast to non-diabetics) are more sensitive to the influence of 19-norprogestogens than to alkylated estrogens, with respect to lipid metabolism.", "It has been reported that women with polycystic ovary syndrome (PCOS) benefit from metformin therapy.\n A randomized, placebo-controlled, double-blind study of obese (body mass index >30 kg/m2), oligo-/amenorrhoeic women with PCOS. Metformin (850 mg) twice daily was compared with placebo over 6 months. All received the same advice from a dietitian. The primary outcome measures were: (i) change in menstrual cycle; (ii) change in arthropometric measurements; and (iii) changes in the endocrine parameters, insulin sensitivity and lipid profile.\n A total of 143 subjects was randomized [metformin (MET) = 69; placebo (PL) = 74]. Both groups showed significant improvements in menstrual frequency [median increase (MET = 1, P < 0.001; PL = 1, P < 0.001)] and weight loss [mean (kg) (MET = 2.84; P < 0.001 and PL = 1.46; P = 0.011)]. However, there were no significant differences between the groups. Logistic regression analysis was used to analyse the independent variables (metformin, percentage of weight loss, initial BMI and age) in order to predict the improvement of menses. Only the percentage weight loss correlated with an improvement in menses (regression coefficient = 0.199, P = 0.047, odds ratio = 1.126, 95% CI 1.001, 1.266). There were no significant changes in insulin sensitivity or lipid profiles in either of the groups. Those who received metformin achieved a significant reduction in waist circumference and free androgen index.\n Metformin does not improve weight loss or menstrual frequency in obese patients with PCOS. Weight loss alone through lifestyle changes improves menstrual frequency.", "This study evaluated the impact of weight on efficacy during use of an extended oral contraceptive (OC).\n Data were from a Phase 3 clinical trial evaluating the efficacy of a low-dose 91-day extended regimen of 100 mcg levonorgestrel/20 mcg ethinyl estradiol (LNG/EE; 84 days)+10 mcg EE (7 days) for the prevention of pregnancy. Crude pregnancy rates were calculated for weight and body mass index (BMI) deciles.\n Of the 1736 women in this analysis, 878 (50.6%) had a BMI greater than 25 kg/m2, and 770 (44.4%) were heavier than 70 kg. Pregnancies occurred in 36 women. Crude pregnancy rates were similar across weight and BMI deciles, with no discernable differences observed between deciles using either classification criterion.\n No evidence of any reduction in the level of contraceptive efficacy was observed with this low-dose extended OC regimen in overweight and obese women.\n Copyright © 2012. Published by Elsevier Inc.", "To compare the adverse effects, cycle control, and metabolic effects of NuvaRing and a combined oral contraceptive (COC).\n Women seeking contraception received NuvaRing (n = 300) or a COC (n = 300) for 12 cycles in a randomized, open-label trial.\n The total number of women with adverse effects did not differ significantly between the 2 groups. Leucorrhea, vaginitis, decreased libido, and ring-related problems were more common with NuvaRing, whereas weight increase, acne, and emotional lability were more common with the COC. Breakthrough bleeding occurred in 11.3% of women receiving NuvaRing and in 14.7% of women receiving the COC; 2.1% and 2.9% of women, respectively, had no withdrawal bleeding. Differences in blood pressure, blood sugar levels, lipid profile, liver enzyme activity, and anticoagulant activity were not statistically significant, with the exception of low-density lipoprotein levels measured at 6 and 12 months, which were significantly lower in the NuvaRing group than in the COC group.\n NuvaRing is a good alternative to a COC. It is associated with a slightly reduced incidence of breakthrough bleeding and there were no clinically relevant adverse effects or changes in blood pressure, blood sugar levels, lipid profile, or anticoagulant activity when compared with the COC.\n Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.", "A prospective randomized trial was conducted to compare efficacy of a drospirenone-containing combined oral contraceptives (COC) with desogestrel-containing COC in women with polycystic ovary-syndrome (PCOS) not desirous of child-bearing.\n Sixty women were randomized into study group [ethinylestradiol (EE) 30 mcg+drospirenone 3 mg] and control group (EE 30 mcg+desogestrel 150 mcg), treated for 6 months and followed up at 1 month, 3 months, 6 months, during treatment and 3 and 6 months post-treatment. Acne and hirsutism scoring, bodyweight, body mass index (BMI), blood pressure (BP), ultrasound parameters, lipid profile, glycemic profile and hormonal profile were compared.\n Cycles were regular in both groups during treatment. Effect of regular cycles persisted in 44.83% (13/30) vs. 17.24% (5/30) in study vs. control group at 6 months post-treatment with 33.3% decreased hirsutism score in the study group (versus no change in control group) even at 6 months after stopping treatment. With treatment, BMI fell by 0.52 kg/m(2) in the study group; systolic and diastolic BP fell in the study group while it rose in the control group. Low-density lipoprotein significantly decreased and high-density lipoprotein was elevated in the study group (p<.05). The study group showed a significant fall in fasting/postprandial blood sugar and insulin and total testosterone against a rise in the control group.\n In women with PCOS, a drospirenone containing COC has better outcome in terms of persistent regular cycles, antiandrogenic effect, fall in BMI and BP, better lipid profile, favorable glycemic and hormonal profile than desogestrel-containing COC.\n Copyright 2010 Elsevier Inc. All rights reserved.", "The objective of this study was to examine body composition changes in adolescent girls initiating depot medroxyprogesterone acetate (DMPA), oral contraceptives, or no hormonal contraceptive method. At 6 months, DMPA resulted in significant increases in adiposity with concomitant decreases in lean body mass. Supplemental estrogen may lessen these DMPA effects.", "Body weight, fasting blood glucose (GP) (BFG), serum immunoreactive insulin (IRI), serum growth hormone (GH) and serum glycosylated proteins were longitudinally followed in 2 groups of women during two years' oral contraception. One group (n = 10) received a combination of 0.030 mg ethinylestradiol and 0.150 mg levonorgestrel and the other (n = 10) a combination of 0.030 mg ethinylestradiol and 0.150 mg of desogestrel. There was a significant increase in BFG during the study and the values were still rising, when examined 2 months after discontinuation of the pill. Two subjects, reaching the level of 5.5 mmol/l showed normal pretreatment values, when investigated one year later. After 6 months' use of either preparation, GH significantly increased, remained on that level throughout the study and returned to the pretreatment level after discontinuation of the pill. Body weight, IRI and GPP did not change significantly during the study.", "To determine in a prospective study if the use of two low-dose estrogen oral contraceptives is associated with changes in weight or body composition.\n 80 outpatients referring to the family planning service, aged 18-43 years were randomly assigned to a treatment with the EE/desogestrel or EE/gestodene association, 20 patients with IUD, aged 26-40 years, were selected as a control group. Anthropometric data and body composition were taken at enrollment and after 6 and 12 months.\n Anthropometric measurements included body mass index (BMI), body composition estimated by mean of Bioelectrical Impendance Analysis (BIA).\n In the three groups weight, BMI, and total body water (TBW), and body cellular mass (BCM) remained unchanged during the study period.\n The use of EE/desogestrel and EE/gestodene is not associated with significant variations of body weight and body composition during one year treatment.", "The metabolic effects of four oral contraceptives with different estrogen/progestogen profiles (monophasic nonalkylated estrogen/norethindrone, low-dose monophasic ethinyl estradiol (EE2)/norethindrone, progestogen only treatment with norethindrone, and triphasic EE2/levonorgestrel) were examined in insulin-dependent diabetic women. During the 6-month study period, no differences were found in fasting plasma glucose, 24-hour insulin requirements, glycated hemoglobin, free fatty acids, low-density lipoprotein cholesterol concentrations, or high-density lipoprotein cholesterol/total cholesterol ratio between the patients in each treatment group. Compared with the nonalkylated estrogen/norethindrone and the triphasic EE2/levonorgestrel formulations, the low-dose EE2/norethindrone combination resulted in small but significant increases in plasma triglyceride and very low-density lipoprotein cholesterol levels (P less than 0.01), which seemed unfavorable from a clinical point of view. Norethindrone-only treatment appeared to be an appropriate alternative to both the nonalkylated estrogen/norethindrone combination and the triphasic EE2/levonorgestrel formulations.", "To estimate the contraceptive failure rates of the etonogestrel subdermal contraceptive implant in overweight and obese women and compare failure rates with women of normal weight and women using intrauterine devices (IUDs).\n The Contraceptive CHOICE Project is a large prospective cohort study designed to promote the use of long-acting reversible contraceptive methods to reduce unintended pregnancies in the St Louis region. Participants are provided reversible contraception of their choice at no cost. We collected baseline height and weight of each participant. During each survey, participants were asked about missed menses and possible pregnancies. Any participant who suspected a pregnancy was asked to come in for urine pregnancy testing. Analysis includes the first 8,445 participants enrolled in CHOICE of which 1,168 chose the implant and 4,200 chose the IUD. Student's t test, χ test, and Kaplan-Meier survival curves were used to perform statistical analyses to estimate failure rates in overweight and obese women using the implant and IUDs.\n Of the women choosing the implant, 28% were overweight and 35% were obese. Of the women who chose an IUD, 27% were overweight and 35% were obese. The 3-year cumulative failure rates for implant and IUD users were less than one per 100 women-years and did not vary by body mass index.\n We found no decrease in the effectiveness of the implant in overweight or obese women. The implant may be offered as a first-line contraceptive method to any woman seeking a reversible and reliable birth control method.", "A comparative study of the metabolic effects of two combined oral contraceptive preparations was undertaken in seven WHO Collaborating Centres for Research in Human Reproduction. A total of 847 subjects were randomly allocated to one of two pill groups - norethisterone lmg/ethinyl estradiol 35 micrograms (NET/EE) or levonorgestrel 150 micrograms/ethinyl estradiol 30 micrograms (LNG/EE). An additional 195 women using an IUD served as a comparison group. Blood samples were taken on admission, and at 3 and 12 months thereafter. Both pills induced changes in fasting and 2-hour glucose, triglycerides, total cholesterol, HDL-cholesterol, bilirubin, alkaline phosphatase, albumin, and total protein, but not aspartate aminotransferase. The most dramatic and probably most clinically important changes were an increase in triglycerides and a decrease in HDL-cholesterol. The NET/EE preparation appeared to induce a greater increase in triglycerides, but no significant difference was found between the two pill preparations with respect to HDL-cholesterol changes.", "This study compared the effects of two triphasic oral contraceptives (OCs) taken for 6 pill cycles. One preparation contained levonorgestrel (EE/LN), the other a new progestagen, gestodene (SHG 415G). There were no effects on body weight, dietary habits, blood pressure, HDL-cholesterol or carbohydrate metabolism. Both OCs caused a small but statistically significant increase in plasma total cholesterol, LDL-cholesterol, LDL/HDL-cholesterol ratio and triglyceride concentration. Sex hormone binding globulin was increased by both preparations. Coagulation factor VII and fibrinogen were increased and antithrombin III levels reduced, indicating that both preparations had pro-coagulant activity. The gestodene triphasic preparation was associated with minor side effects similar to those experienced on EE/LN. The metabolic effects were similar despite the lower total steroid dose of the gestodene preparation.", "Depo-medroxyprogesterone acetate (DMPA) is an increasingly popular contraceptive choice among Navajo women. Weight gain is cited as a common side effect and major reason for discontinuation of DMPA. No controlled trials have evaluated the association between weight gain and DMPA in Navajo women. We aimed to clarify whether DMPA is associated with weight gain in Navajo women and to quantify the magnitude of weight gain. A cohort of 172 Navajo women who had used DMPA continuously for one or 2 years comprised the study group. A cohort of 134 Navajo women who used a non-progestin method or no method over 1 or 2 years comprised the comparison group. Initial weight, one-year weight and 2-year weights were recorded for all patients. Study subjects gained a mean of 6 pounds over one year and 11 pounds over 2 years relative to the comparison group (p < 0.001) after controlling for possible confounding variables including age, parity and initial weight. Use of DMPA is associated with significant weight gain in Navajo women. This weight gain is greater than that reported in previous uncontrolled studies in non-Navajo populations. This information should be utilized in counseling Navajo women about the side effects of DMPA.", "A comparative multicenter clinical trial of two low-dose combined oral contraceptives (OCs) was conducted in Malaysia, Egypt, Thailand, and Mexico. Efficacy, safety and acceptability were investigated in women taking either a norgestrel-based (NG) OC or a norethindrone acetate-based (NA) OC. This paper includes analysis of 892 women, all of whom were at least 42 days but within 26 weeks postpartum and randomly allocated to one of the above OCs. Follow-up visits were scheduled at 1, 4, 8 and 12 months after admission. Baseline sociodemographic characteristics were similar for both groups, as well as compliance. There were nine unintended pregnancies reported; eight of these occurring in the NA group. Adverse experiences were minor with headaches and dizziness being the most common complaints; frequency of reports was similar in both groups. The group taking the NG-based OC had significantly (p < .05) fewer menstrual-related complaints. Discontinuations due to menstrual problems were significantly more common among NA users (primarily amenorrhea). Discontinuations in the NG group were primarily for other personal reasons, e.g. unable to return to the clinic. There was also a significant difference between the two groups for the 11-month gross cumulative life table discontinuation rates due to menstrual problems (p < .01); the NA group had the higher rate.", "The study was conducted to investigate whether hormonal contraceptives administered via the oral and vaginal route exert a similar effect on insulin sensitivity (SI).\n This is a prospective, randomized study performed in the University Hospital. Subjects were healthy lean young women, needing a hormonal contraceptive, randomly allocated to receive for 6 months (a) an oral contraceptive (OC) containing 30 mcg ethinylestradiol (EE)/150 mcg desogestrel (DSG) (high-estrogen group; n=12), (b) an OC containing 20 mcg EE/150 mcg DSG (low-estrogen group; n=12) and (c) a vaginal ring contraceptive releasing, per day, 15 mcg EE/120 mcg etonorgestrel, the active DSG metabolite (n=12). SI and glucose utilization independent of insulin (Sg) were evaluated by the minimal model method. Modifications of total, high-density lipoprotein (HDL) and low-density lipoprotein cholesterol and triglycerides were also evaluated.\n Sg did not vary with any treatment. SI decreased during OCs (5.74+/-0.49 vs. 3.86+/-0.44; p=.0005), independently of the high/low-estrogen dose. SI did not decrease during vaginal ring use (4.64+/-1.03 vs. 5.25+/-1.36; p=.57; p=.019 vs. oral). Total cholesterol and HDL cholesterol increased (p=.02) during OCs, independently of the dose. Triglycerides increased during both oral (p=.01) and vaginal (p=.032) contraceptive use.\n The present data indicate that in contrast to OC use, vaginal contraception with the ring does not deteriorate SI. The vaginal ring may represent an appropriate choice for long-term contraception in women at risk for developing diabetes mellitus or metabolic syndrome.", "A randomized double-blind study of the metabolic effects of 2 low-dose combined oral contraceptives was carried out in Singaporean women. The subjects comprised 58 women randomly allocated to two treatment groups (29 each): norethisterone 1 mg/ethinyl estradiol 35 micrograms (NET/EE) or levonorgestrel 150 micrograms/ethinyl estradiol 30 micrograms (LNG/EE) and a control group of 23 women using intra-uterine devices (IUD). Blood samples were taken on admission and at 3 and 12 months after pills or insertion of IUDs. Fasting glucose levels were decreased while 2h glucose and triglyceride were increased throughout the treatment period in NET/EE group [corrected]. LNG/EE group only showed significant increase of 2h glucose at 12 months and decrease of LDL cholesterol at 3 months while total cholesterol was significantly suppressed at 3 and 12 months [corrected]. The atherogenic index, LDL/HDL cholesterol was significantly reduced by 12 months. Both groups had no change in hemoglobin, hematocrit and total protein levels but alkaline phosphatase, bilirubin and aspartate transaminase (SGOT) were suppressed. While NET/EE suppressed albumin significantly, this was not observed with LNG/EE group. However, these differences observed with use of each pill preparations, were not so obvious between treatment groups and control. Changes in total, HDL and LDL cholesterol and SGOT were not significantly different than the IUD group. Furthermore, except for 2h glucose, there was no increase in the number of abnormal parameters after treatment. On the contrary, there was a reduction of abnormal values in most liver function parameters. Thus, except for glucose intolerance, the observed changes in metabolic parameters may not constitute any clinical significance.(ABSTRACT TRUNCATED AT 250 WORDS)", "This study compared the impact on carbohydrate metabolism of two combinedoral contraceptives (COCs). This open-label, single-center trial enrolled participants for a total of 15 cycles. Thirty-six women were randomized to receive either 20 microg ethinyl estradiol (EE) and 75 microg gestodene (GSD) or 20 microg ethinyl estradiol and 150 microg desogestrel (DSG) daily for 21 days out of 28. A glucose tolerance test was performed at baseline and cycles 6 and 13. The area under the curve (AUC) for glucose increased in both study groups. The change was statistically significant (p = 0.036) for the 20 EE/75 GSD group at cycle 6 versus baseline. Fasting blood glucose at cycle 13 was significantly (p < 0.01) higher for both treatment groups compared to baseline. No changes were found for fasting insulin and fasting C-peptide levels or for the AUCs of insulin or C-peptide. Both regimens were well tolerated. Gestodene and desogestrel in combination with 20-microg ethinyl estradiol induce similar changes in carbohydrate metabolism which are smaller than those described earlier for COCs containing higher estrogen doses or more androgenic progestins such as levonorgestrel.\n Copyright 2002 Elsevier Science Inc.", "To compare weight and continuation among adolescents using monthly medroxyprogesterone acetate (MPA)/ethinyl estradiol cypionate (E2C), tri-monthly depot MPA (DMPA), and daily oral contraceptive pills (OCP).\n Medical records were reviewed for body mass index, demographics, and sexual history at baseline; and weight and continuation at 3, 6, 9, and 12 months. Bivariate analyses were performed by method, and continuation functions were compared by the log-rank and Wilcoxon tests. The effect of method on use duration was assessed by Cox regression.\n Hospital adolescent clinic.\n 12- to 21-year-old patients who initiated MPA/E2C, DMPA, or OCPs in 2001.\n Weight gain and method continuation.\n MPA/E2C was initiated by 40 (18%) patients, DMPA by 63 (28%), and OCPs by 119 (54%, P < 0.001). OCP users were younger (P = 0.005) and more likely to be white, privately insured, and in school (P < 0.004) than MPA/E2C or DMPA users. Previous DMPA and OCP use, pregnancy, and sexually transmitted infections (STI) were more common among MPA/E2C than DMPA or OCP users (P < or = 0.001). Baseline BMI was lowest (P = 0.06) among DMPA users, and MPA/E2C users were most likely to be overweight (P = 0.03). There were non-significant differences in weight change. Continuation functions differed by the method only in the first three months of use (P = 0.03). Leading reasons for discontinuation were unavailability of MPA/E2C (20%), bleeding with DMPA (22%), and forgetting OCPs (17%). Duration of use was independently associated with white race (P < 0.005) and STI-never (P < 0.0001) but not with method type.\n Although MPA/E2C use was associated with overweight status and early discontinuation, it also was associated with previous use of other methods. For all methods, poor continuation at one year supports the ongoing search for effective contraceptive alternatives.", "To compare the effects of a combined oral contraceptive (COC) containing nomegestrol acetate and 17β-oestradiol (NOMAC/E2) on haemostasis, lipids, carbohydrate metabolism, C-reactive protein (CRP) and sex hormone-binding globulin (SHBG) with those of a COC containing levonorgestrel and ethinylestradiol (LNG/EE).\n In a randomised, open-label study, 121 healthy women, 18-50 years of age, were randomly assigned to receive NOMAC/E2 (2.5 mg/1.5 mg) in a 24/4-day regimen (n=60) or LNG/EE (150 μg/30 μg) in a 21/7-day regimen (n=61) for six cycles. The primary outcome was the change from baseline to cycle 6 for all indices.\n All parameters were similar at baseline between the two groups. Over six cycles, NOMAC/E2 had less effect on most haemostatic indices than LNG/EE. Lipids were essentially unchanged with NOMAC/E2, whereas with LNG/EE high-density lipoprotein cholesterol decreased and low-density lipoprotein cholesterol and triglycerides slightly increased. NOMAC/E2 induced negligible changes in glucose and insulin parameters, in contrast to LNG/EE. A much smaller increase in CRP was observed with NOMAC/E2 than with LNG/EE. NOMAC/E2 was associated with a greater increase in SHBG.\n The monophasic COC NOMAC/E2 had less influence on haemostasis, lipids and carbohydrate metabolism than the COC LNG/EE.", "To obtain data from a pilot randomized trial on the effect of metformin therapy and lifestyle modification on ovulation and androgen concentrations in women with polycystic ovary syndrome (PCOS).\n Prospective, randomized, placebo-controlled pilot trial.\n Academic medical center.\n Thirty-eight overweight or obese women with PCOS.\n All subjects were randomized to one of four 48-week interventions: metformin 850 mg two times per day, lifestyle modification plus metformin 850 mg two times per day, lifestyle modification plus placebo, or placebo alone.\n Recruitment, dropout, and compliance with a long-term lifestyle intervention in PCOS; preliminary estimates of treatment effect on ovulation, as measured by weekly urinary pregnanediol glucuronide, and on total T and free androgen index.\n It was necessary to screen seven women to have one subject randomized. The dropout rate was 39%, with the majority of dropouts occurring within the first 24 weeks. Mean body mass index was >39 mg/kg(2). Modest weight reduction was found in all treatment groups, with the most significant reduction occurring with the combination of metformin and lifestyle intervention. Significant androgen reduction occurred in the combination group only. Ovulation rates did not differ significantly between groups. However, when data were analyzed by presence or absence of weight reduction in subjects, independent of treatment group, the estimated odds ratio for weight loss was 9.0 (95% confidence interval 1.2-64.7) with respect to regular ovulation. If weight loss occurred during metformin therapy, the odds ratio for regular ovulation was 16.2 (95% confidence interval 4.4-60.2).\n Key methodologic issues for a large-scale, randomized trial of lifestyle intervention in PCOS include minimizing early dropout from the lifestyle intervention and including a range of body mass index that is not skewed toward severe obesity. Weight reduction might play the most significant role in restoration of ovulation in obese women with PCOS.", "WHO conducted a three-centre study in Hungary and Thailand to evaluate the effects of hormonal contraception on lactation and infant growth. Women choosing oral contraceptives were randomly assigned to a combined oral contraceptive containing 30 micrograms ethinyl estradiol and 150 micrograms levonorgestrel (N = 86) or a progestin-only preparation containing 75 micrograms dl-norgestrel (N = 85). Identical packaging and treatment schedules allowed double-blind observation. One-hundred-and-eleven women using no contraception or non-hormonal methods acted as controls. In the two Thai centres 59 women using depot-medroxyprogesterone acetate formed an additional comparison group. All subjects were healthy women with normal deliveries, whose infants had normal birth weights and satisfactory growth in the neonatal period. Breast milk volume was determined by pump expression using standardized procedures. Information was obtained on nursing frequency and supplementation, infant growth and morbidity. Pretreatment observations at 6 weeks post-partum were used as a baseline, and subjects were followed-up at 9, 12, 16, 20 and 24 weeks post-partum. Women using combined oral contraceptives had a decline in milk volume within 6 weeks of initiating treatment, whereas no significant decrease was observed in the other treatment groups. After 18 weeks of treatment, combined oral contraceptive users experienced a 41.9% decline in milk volume, compared to 12.0% with progestin-only minipills and 6.1% in the non-hormonal controls. The prevalence of complementary feeding and withdrawals due to inadequate milk supply were comparable in the four treatment groups. However, data were not available on the daily amounts of complementary feeds. There were no significant differences in growth of infants between treatment groups. Thus, women may have compensated for declines in milk volume by more supplementary feeding or by more prolonged and intense suckling episodes. We conclude that 30 micrograms estrogen-containing combined oral contraceptives impair milk secretion, but in the selected healthy group of mothers and children studied with the prevailing level of supplementary feeding, this did not adversely affect infant growth.", "This paper investigates the relationship between pregnancy rates and body weight of 1005 women using a vaginal ring releasing 20 micrograms levonorgestrel per 24 hours. While the overall pregnancy rate at one year was 3.7%, it was found that women have an increasing risk of pregnancy with increasing body weight. For example, a woman of 40 kg has an estimated pregnancy rate of 1.7% in contrast to 9.8% for a woman of 80 kg weight.", "This study compared metabolic, hormonal and lipid profiles before and during use of a contraceptive vaginal ring (RING) releasing 15 mcg ethinyl estradiol (EE) and 120 mcg etonogestrel per day NuvaRing, Organon USA Inc., Roseland, NJ versus a low-dose oral contraceptive (PILL) containing 20 mcg EE and 100 mcg levonorgestrel daily (Aviane, Barr Pharmaceuticals Inc., Pomona, NY).\n Sixty-five women were randomized to either the RING or PILL treatment for five cycles. In the pretreatment cycle (Cycle Days 2-5) and during Weeks 2 and 3 of the fifth treatment cycle, a 75-g oral glucose tolerance test (OGTT) was performed. Baseline samples were used to evaluate basal hormonal, metabolic and lipid levels.\n Forty-two women completed the study. Basal insulin resistance (HOMA-IR) was slightly decreased, whereas a significant reduction in the insulin sensitivity index (IS(OGTT)) was found in women on PILL therapy compared to those in the RING group (p<.035). Pancreatic beta-cell function was not significantly altered with either treatment.\n The lower-dose, nonoral hormonal RING had a lesser impact on carbohydrate metabolism and greater reduction of free androgen and dehydroepiandrosterone sulfate levels than PILL treatment.", "A 6-month single-blind study compared the use of a progestagen-only oral contraceptive containing norethisterone 350 micrograms/day (NE 350) with one containing levonorgestrel 30 micrograms (LN 30), to assess the metabolic effects. At the end of 6 months, there were no significant differences between the two groups with respect to plasma cholesterol, lipoproteins including HDL subfractions, triglycerides or glucose concentration. Levels of fibrinogen, plasminogen, Factor VII, Factor X and antithrombin III were also similar. Women changing from a combined oral contraceptive to LN 30 showed a significant fall in Factor X. Mean blood pressure fell on LN 30 by 7/9 mmHg, but the 6-month reading did not differ significantly from that in women on NE 350. Acceptability, and the metabolic effects of the two preparations were similar in this study. Further larger studies are warranted.", "The objective of this study was to compare cycle control, cycle-related characteristics and bodyweight effects of NuvaRing with those of a combined oral contraceptive (COC) containing 30 microg of ethinyl estradiol and 3 mg of drospirenone.\n A randomized, multicentre, open-label trial in which 983 women were treated (intent-to-treat population) with NuvaRing or the COC for 13 cycles.\n Breakthrough bleeding or spotting during cycles 2-13 was in general less frequent with NuvaRing than that with the COC (4.7-10.4%) and showed a statistically significant odds ratio of 0.61 (95% confidence interval: 0.46, 0.80) with longitudinal analysis. Intended bleeding was significantly better for all cycles with NuvaRing (55.2-68.5%) than that with the COC (35.6-56.6%) (P < 0.01). Changes from baseline in mean bodyweight and body composition parameters were relatively small for both groups with no notable between-group differences.\n NuvaRing was associated with better cycle control than the COC, and there was no clinically relevant difference between the two groups in bodyweight.", "Neither oral contraceptives (COC) nor metformin are an optimal modality for the long-term treatment of polycystic ovary syndrome (PCOS). The aim of this study was to evaluate whether a combination of both is beneficial over COC monotherapy.\n Altogether, 30 women were included in the study and 28 finished the protocol. The patients were randomly assigned to two groups treated with either COC (COC group) or COC and metformin (1500 mg/day) (METOC group) for 6 months. Anthropometric parameters, androgens, lipids, fasting insulin, glucose and sex hormone binding globulin (SHBG) concentrations were measured before and at the end of the sixth cycle of treatment. The insulin sensitivity index was evaluated using the euglycaemic clamp.\n There were no significant changes in anthropometric parameters, fasting glucose or insulin sensitivity in either group. Total testosterone, free androgen index, androstenedione and dehydroepiandrosterone decreased and SHBG increased significantly in both groups. When comparing the effect of both treatments, only a more pronounced decrease in free androgen index was found in the METOC group.\n Adding metformin slightly modified the treatment effect of COC, causing a more significant decrease in the free androgen index but having no additional positive impact on lipids, insulin sensitivity, SHBG or testosterone. The available data do not offer enough evidence to advocate the standard use of combined treatment in PCOS. Whether the combination might be beneficial for specific subgroups of patients is of further interest." ]	Available evidence was insufficient to determine the effect of combination contraceptives on weight, but no large effect was evident. Trials to evaluate the link between combination contraceptives and weight change require a placebo or non-hormonal group to control for other factors, including changes in weight over time.
CD008589	[ "7033847" ]	[ "Lactation suppression with bromocriptine." ]	[ "The efficacy and acceptability of bromocriptine in suppressing postpartum lactation was determined in a double blind study in which bromocriptine 2.5 mg twice daily for 14 days was compared with a placebo. Forty women who decide during the antenatal period not to breast feed entered the study. The bromocriptine treated group had significantly less mammary secretion and breast engorgement than the control group and also required less analgesia. The most noticeable side effects during the trial were dizziness, headache and abdominal pain. The only statistical difference between the two groups was a higher incidence of dizziness in the bromocriptine treated group." ]	There are insufficient data to draw any firm conclusions. Treatment with bromocriptine appears promising, although women would be unable to breastfeed due to suppression of lactation.
CD000102	[ "16816557", "10485720", "10199349", "12599045", "15247338" ]	[ "Maternal single-dose nevirapine versus placebo as part of an antiretroviral strategy to prevent mother-to-child HIV transmission in Botswana.", "Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial.", "Elective caesarean-section versus vaginal delivery in prevention of vertical HIV-1 transmission: a randomised clinical trial.", "A multicenter randomized controlled trial of nevirapine versus a combination of zidovudine and lamivudine to reduce intrapartum and early postpartum mother-to-child transmission of human immunodeficiency virus type 1.", "Single-dose perinatal nevirapine plus standard zidovudine to prevent mother-to-child transmission of HIV-1 in Thailand." ]	[ "Single-dose nevirapine given to women and infants reduces mother-to-child HIV transmission, but nevirapine resistance develops in a large percentage of women.\n To determine whether the maternal nevirapine dose could be eliminated in the setting of zidovudine prophylaxis.\n A 2 x 2 factorial, randomized, clinical trial, with a double-blinded peripartum factor designed to assess the equivalence of maternal single-dose nevirapine versus placebo with respect to HIV transmission. A total of 709 HIV-infected pregnant women were randomized from four district hospitals in Botswana, resulting in 694 live first-born infants. HAART was available for women with AIDS.\n All women received a background of zidovudine from 34 weeks' gestation through delivery, and all infants received single-dose nevirapine at birth and zidovudine from birth through 1 month. Women were randomized to receive either single-dose nevirapine or placebo during labor.\n The primary endpoint was infant HIV infection by the 1-month visit.\n Of the 694 infants in this equivalence study, 15 (4.3%) of 345 in the maternal nevirapine arm were HIV infected by 1 month, versus 13 (3.7%) of 349 in the maternal placebo arm (95% confidence interval for difference, -2.4% to 3.8%), meeting pre-determined equivalence criteria. Nevirapine resistance at 1 month postpartum was detected in 45% of a random sample of women who received nevirapine.\n In the setting of maternal zidovudine and infant zidovudine plus single-dose nevirapine, infant HIV infection rates were similar whether women received single-dose nevirapine or placebo. This strategy avoids the potential for maternal nevirapine resistance.", "The AIDS Clinical Trials Group protocol 076 zidovudine prophylaxis regimen for HIV-1-infected pregnant women and their babies has been associated with a significant decrease in vertical HIV-1 transmission in non-breastfeeding women in developed countries. We compared the safety and efficacy of short-course nevirapine or zidovudine during labour and the first week of life.\n From November, 1997, to April, 1999, we enrolled 626 HIV-1-infected pregnant women at Mulago Hospital in Kampala, Uganda. We randomly assigned mothers nevirapine 200 mg orally at onset of labour and 2 mg/kg to babies within 72 h of birth, or zidovudine 600 mg orally to the mother at onset of labour and 300 mg every 3 h until delivery, and 4 mg/kg orally twice daily to babies for 7 days after birth. We tested babies for HIV-1 infection at birth, 6-8 weeks, and 14-16 weeks by HIV-1 RNA PCR. We assessed HIV-1 transmission and HIV-1-free survival with Kaplan-Meier analysis.\n Nearly all babies (98.8%) were breastfed, and 95.6% were still breastfeeding at age 14-16 weeks. The estimated risks of HIV-1 transmission in the zidovudine and nevirapine groups were: 10.4% and 8.2% at birth (p=0.354); 21.3% and 11.9% by age 6-8 weeks (p=0.0027); and 25.1% and 13.1% by age 14-16 weeks (p=0.0006). The efficacy of nevirapine compared with zidovudine was 47% (95% CI 20-64) up to age 14-16 weeks. The two regimens were well tolerated and adverse events were similar in the two groups.\n Nevirapine lowered the risk of HIV-1 transmission during the first 14-16 weeks of life by nearly 50% in a breastfeeding population. This simple and inexpensive regimen could decrease mother-to-child HIV-1 transmission in less-developed countries.", "Results from observational studies suggest that caesarean-section delivery may reduce the risk of mother-to-child transmission of HIV-1 infection in comparison with vaginal delivery. We carried out a randomised clinical trial to address this issue and to assess the extent of postdelivery complications.\n Eligible women were between 34 and 36 weeks of pregnancy, with a confirmed diagnosis of HIV-1 infection, and without an indication for caesarean-section delivery or a contraindication to this mode of delivery. Women were randomly assigned elective caesarean-section delivery at 38 weeks of pregnancy or vaginal delivery. An infant was classified as uninfected if he or she became negative for antibody to HIV-1 by age 18 months or was negative for virus by PCR or culture on at least two occasions, with no clinical, immunological, or viral evidence of infection. From 1993, to March, 1998, 436 women were randomised.\n We present the results of an analysis updated to November, 1998, with data on the infection status of 370 infants. Three (1.8%) of 170 infants born to women assigned caesarean-section delivery were infected, compared with 21 (10.5%) of 200 born to women assigned vaginal delivery (p<0.001). Seven (3.4%) of 203 infants of women who actually gave birth by caesarean section were infected compared with 15 (10.2%) of 167 born vaginally (p=0.009). There were few postpartum complications and no serious adverse events in either group.\n Our findings provide evidence that elective caesarean-section delivery significantly lowers the risk of mother-to-child transmission of HIV-1 infection without a significantly increased risk of complications for the mother.", "To determine the efficacy and safety of 2 inexpensive and easily deliverable antiretroviral (ARV) regimens for the prevention of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) type 1 during labor and delivery, HIV-infected pregnant women were screened at 11 maternity health institutions in South Africa and were enrolled in an open-label short course ARV regimen of either nevirapine (Nvp) or multiple-dose zidovudine and lamivudine (Zdv/3TC). The overall estimated HIV-1 infection rates in 1307 infants by 8 weeks were 12.3% (95% confidence interval [CI], 9.7-15.0) for Nvp and 9.3% (95% CI, 7.0-11.6) for Zdv/3TC (P=.11). Excluding infections detected within 72 h (intrauterine), new HIV-1 infections were detected in 5.7% (95% CI, 3.7-7.8) and 3.6% (95% CI, 2.0-5.3) of infants in the Nvp and Zdv/3TC groups, respectively, in the 8 weeks after birth. There were no drug-related maternal or pediatric serious adverse events. Common complications were obstetrical for mothers (Nvp group, 24.3%; Zdv/3TC group, 26.3%) and respiratory for infants (Nvp group, 16.1%; Zdv/3TC group, 17.0%). This study further confirms the efficacy and safety of short-course ARV regimens in reducing MTCT rates in developing countries.", "Although zidovudine prophylaxis decreases the rate of transmission of the human immunodeficiency virus (HIV) type 1 substantially, a large number of infants still become infected. We hypothesized that the administration, in addition to zidovudine, of a single dose of oral nevirapine to mothers during labor and to neonates would further reduce transmission of HIV.\n We conducted a randomized, double-blind trial of three treatment regimens in Thai women who were receiving zidovudine therapy during the third trimester of pregnancy. In one group, mothers and infants received a single dose of nevirapine (nevirapine-nevirapine regimen); in another, mothers and infants received nevirapine and placebo, respectively (nevirapine-placebo regimen); and in the last, mothers and infants received placebo (placebo-placebo regimen). The infants also received one week of zidovudine therapy and were formula-fed. The end point of the study was infection with HIV in the infants, established by virologic testing.\n Between January 15, 2001, and February 28, 2003, a total of 1844 Thai women were enrolled. At the first interim analysis, the independent data monitoring committee stopped enrollment in the placebo-placebo group. Among women who delivered before the interim analysis, the as-randomized Kaplan-Meier estimates of the transmission rates were 1.1 percent (95 percent confidence interval, 0.3 to 2.2) in the nevirapine-nevirapine group and 6.3 percent (95 percent confidence interval, 3.8 to 8.9) in the placebo-placebo group (P<0.001). The final per-protocol transmission rate in the nevirapine-nevirapine group, 1.9 percent (95 percent confidence interval, 0.9 to 3.0), was not significantly inferior to the rate in the nevirapine-placebo group (2.8 percent; 95 percent confidence interval, 1.5 to 4.1). Nevirapine had an effect within subgroups defined by known risk factors such as viral load and CD4 count. No serious adverse effects were associated with nevirapine therapy.\n A single dose of nevirapine to the mother, with or without a dose of nevirapine to the infant, added to oral zidovudine prophylaxis starting at 28 weeks' gestation, is highly effective in reducing mother-to-child transmission of HIV.\n Copyright 2004 Massachusetts Medical Society" ]	Zidovudine, nevirapine and delivery by elective caesarean section appear to be very effective in decreasing the risk of mother-to-child transmission of HIV infection.
CD005089	[ "4000778", "1552399", "7798839", "10103305", "15123865" ]	[ "Neonatal hyperviscosity: randomized study of effect of partial plasma exchange transfusion on long-term outcome.", "Asymptomatic syndrome of polycythemic hyperviscosity: effect of partial plasma exchange transfusion.", "Developmental outcome of infants with neonatal polycythemia.", "A randomized, controlled trial of prophylactic granulocyte-macrophage colony-stimulating factor in human newborns less than 32 weeks gestation.", "Effect of partial exchange transfusion in asymptomatic polycythemic LBW babies." ]	[ "The use of partial plasma exchange transfusion in newborns with polycythemia and hyperviscosity was evaluated. Ninety-three infants with polycythemia and hyperviscosity were randomly assigned to receive either partial plasma exchange transfusion or symptomatic treatment; the infants were matched with control infants without polycythemia. Neonatal course and outcome at 1 and 2 years were evaluated for each of the three groups. Polycythemic infants had more fine motor and speech problems at 1 year of age than did control infants. At 2 years of age, polycythemic infants had more gross motor delays, neurologic diagnoses, fine motor abnormalities, and speech delays than did the control infants. There was no significant difference at 1 year between the polycythemic infants who had received partial plasma exchange transfusion and those given only symptomatic care. At 2 years, the group receiving partial plasma exchange transfusion had fewer neurologic diagnoses and fine motor abnormalities.", "We determined the cerebral hemodynamic changes in infants with asymptomatic polycythemic hyperviscosity syndrome and whether treatment with partial plasma exchange transfusion (PPET) would affect hemodynamics as well as outcome. From a routine cord blood hematocrit screening, 71 babies were identified as needing to be tested for polycythemic hyperviscosity. In addition to clinical evaluation, each infant had radial artery hematocrit and viscosity determinations, blood gas determinations, cerebral blood flow velocity studies, cranial ultrasonography, and noninvasive intracranial pressure determination. Babies with symptomatic hyperviscosity (n = 17) were treated by PPET, whereas those with asymptomatic hyperviscosity (n = 28) were randomly selected to have PPET (n = 14) or to be observed (n = 14). The remaining babies (n = 26) with normal viscosity served as control subjects. Both hematocrit and viscosity decreased after PPET but remained unchanged in babies with hyperviscosity who were merely observed. Reversal of cerebral blood flow velocity abnormalities was observed after PPET in the infants with symptomatic hyperviscosity, whereas those who had no symptoms had normal results on Doppler studies at the outset, and no significant changes occurred with either PPET or observation. There were two deaths in the group with symptoms. A total of 46 babies returned for follow-up evaluation at a mean age of 30 +/- 7.7 months. Outcome of the control group was no better than that of those who had hyperviscosity, and outcomes did not differ between the babies with symptomatic and those with asymptomatic hyperviscosity, nor between those treated with PPET and those who were only observed. Multivariate analysis revealed that other perinatal risk factors and race rather than polycythemia or PPET, significantly influenced long-term outcome.", "The study of the developmental outcome of neonatal polycythemia was performed on 47 polycythemic and 21 controlled infants who were born at the same period of time. It was found that at the age of 1 1/2 to 2 years the number of infants with abnormal DQ was higher in the group of total polycythemic infants (47%) and in the group of asymptomatic polycythemic infants (45%) than that of the control groups (19% and 5.6% of the groups including twin sibs and excluding twin sibs respectively). There was no difference in the developmental test between the symptomatic and asymptomatic patients. In asymptomatic infants the benefit of partial plasma exchange transfusion on developmental outcome was not found and only low birthweight and small for gestational age infants are the risk factors for poor developmental outcome.", "Preterm neonates undergoing intensive care have high morbidity from sepsis. These infants also frequently develop neutropenia, and when this is associated with sepsis, mortality is high. This study investigates the potential for granulocyte-macrophage colony-stimulating factor (GM-CSF) to effect a clinically relevant increase in neutrophil number when used prophylactically in high-risk preterm neonates, and assesses its safety in this population.\n In an open, randomized, controlled study, 75 neonates (25 small for gestational age) <32 weeks gestation were randomized to receive GM-CSF (10 microg/kg/d) by subcutaneous injection for 5 days from <72 hours after birth, or to a control group. The primary outcome measure was the neutrophil count during 14 days from study entry. The infants were monitored for potential toxicity. Clinical outcomes, sepsis, and mortality, were recorded, but this initial study was not designed to address clinical benefit.\n Prophylactic GM-CSF therapy completely abolished neutropenia in treated infants, when both well and septic, throughout the period of study. Neutropenia (</=1.7 x 10(9)/L) developed in 16 of 39 control infants. Five control infants experienced an acute decrease in neutrophil count coincident with the onset of sepsis. There was no evidence of hematologic, respiratory, or gastrointestinal toxicity in treated infants. Treated infants had a trend to fewer symptomatic, blood culture positive septic episodes than controls during 2 weeks from study entry (11/36 vs 18/39).\n Five-day prophylactic GM-CSF completely abolishes postnatal neutropenia and sepsis-induced neutropenia in preterm neonates at high risk of sepsis, and so removes an important risk factor for sepsis and sepsis-related mortality.GM-CSF, preterm neonates, neutropenia, sepsis.", "This randomized controlled trial was conducted to determine the effect of partial exchange transfusion in polycythemic babies. Forty five asymptomatic polycythemic babies with birth weight < or = 2000 g were included and randomly assigned to undergo either partial exchange transfusion using isotonic saline within 4 hours of screening or routine medical management. Outcome measures were neonatal morbidity (especially hypoglycemia and neurological alterations) and mortality; developmental delays using DDST-II, neurological deficits, tone and DTR abnormalities over 18 months follow up period. The overall neonatal morbidity in this study was low and comparable in the two groups. Some of the polycythemic babies in the non-exchanged group found initially at 3 months age with \"suspected development\" grew out of their developmental delay at 18 months of age or later while those who underwent exchange transfusion and with retarded development at 3 months of age remained so even at 18 months of age." ]	There are no proven clinically significant short or long-term benefits of PET in polycythemic newborn infants who are clinically well or who have minor symptoms related to hyperviscosity. PET may lead to an increase in the risk of NEC. The data regarding developmental follow-up are extremely imprecise due to the large number of surviving infants who were not assessed and, therefore, the true risks and benefits of PET are unclear.
CD007459	[ "21252632", "18984496", "16241873", "16859871" ]	[ "Mobile phone technologies improve adherence to antiretroviral treatment in a resource-limited setting: a randomized controlled trial of text message reminders.", "Use of text messaging for monitoring sugar-sweetened beverages, physical activity, and screen time in children: a pilot study.", "A randomized, controlled trial of an automated wireless messaging system for diabetes.", "A randomised control trial of a self-management program for people with a chronic illness from Vietnamese, Chinese, Italian and Greek backgrounds." ]	[ "There is limited evidence on whether growing mobile phone availability in sub-Saharan Africa can be used to promote high adherence to antiretroviral therapy (ART). This study tested the efficacy of short message service (SMS) reminders on adherence to ART among patients attending a rural clinic in Kenya.\n A randomized controlled trial of four SMS reminder interventions with 48 weeks of follow-up.\n Four hundred and thirty-one adult patients who had initiated ART within 3 months were enrolled and randomly assigned to a control group or one of the four intervention groups. Participants in the intervention groups received SMS reminders that were either short or long and sent at a daily or weekly frequency. Adherence was measured using the medication event monitoring system. The primary outcome was whether adherence exceeded 90% during each 12-week period of analysis and the 48-week study period. The secondary outcome was whether there were treatment interruptions lasting at least 48 h.\n In intention-to-treat analysis, 53% of participants receiving weekly SMS reminders achieved adherence of at least 90% during the 48 weeks of the study, compared with 40% of participants in the control group (P = 0.03). Participants in groups receiving weekly reminders were also significantly less likely to experience treatment interruptions exceeding 48 h during the 48-week follow-up period than participants in the control group (81 vs. 90%, P = 0.03).\n These results suggest that SMS reminders may be an important tool to achieve optimal treatment response in resource-limited settings.", "To examine acceptability, attrition, adherence, and preliminary efficacy of mobile phone short message service (SMS; text messaging) for monitoring healthful behaviors in children.\n All randomized children received a brief psychoeducational intervention. They then either monitored target behaviors via SMS with feedback or via paper diaries (PD) or participated in a no-monitoring control (C) for 8 weeks.\n University of North Carolina at Chapel Hill.\n Fifty-eight children (age 5-13) and parents participated; 31 completed (SMS: 13/18, PD: 7/18, C: 11/22).\n Children and parents participated in a total of 3 group education sessions (1 session weekly for 3 weeks) to encourage increasing physical activity and decreasing screen time and sugar-sweetened beverage consumption.\n Treatment acceptability, attrition, and adherence to self-monitoring.\n Descriptive statistics and nonparametric tests were used to analyze differences across time and group.\n Children in SMS had somewhat lower attrition (28%) than both PD (61%) and C (50%), and significantly greater adherence to self-monitoring than PD (43% vs 19%, P < .02).\n Short message service may be a useful tool for self-monitoring healthful behaviors in children, although the efficacy of this approach needs further study. Implications suggest that novel technologies may play a role in improving health.", "Aggressive management of blood glucose reduces future diabetes-related complications, but this is difficult to achieve.\n This randomized, controlled study tested the effect of using a wireless two-way pager-based automated messaging system to improve diabetes control through facilitated self-management. The system sent health-related messages to patients, with automatic forwarding of urgent patient responses to the health care team.\n Participants in both the experimental (pager) and the control groups experienced an average hemoglobin A1c decrease of 0.1-0.3%. More patients in the pager group were normotensive, and more felt that their health care was better by the end of the study. A total of 79% of participants enjoyed using the pager, and 68% wanted to continue using the system.\n Utilizing a wireless, automated messaging system in clinical practice is a feasible, low-cost, interactive way to facilitate diabetes self-management, which is acceptable to patients. While providing a convenient way for patients and providers to communicate, this system can support automated recording and ready retrieval of these real-time interactions.", "This study investigated the effectiveness of the Chronic Disease Self-management Program (CDSMP) when delivered to for people from Vietnamese, Chinese, Italian and Greek backgrounds living in Victoria, Australia.\n The CDSMP was administered to 320 people with chronic illnesse(es) in selected low income areas in the State of Victoria, Australia. At 6 months, they were compared with randomised wait-list control subjects (n=154) using analyses of covariance.\n Participants in the intervention group had significantly better outcomes on energy, exercise, symptom management, self-efficacy, general health, pain, fatigue and health distress. There were no significant effects for health services utilisation. Interactions across language groups were observed with the Vietnamese and Chinese speaking participants gaining greater benefit.\n Self-management programs can be successfully implemented with culturally and linguistically diverse populations in Australia. Further research is needed to evaluate long-term outcomes; explore effects on service utilisation; and to determine whether the benefits obtained from participating in a self-management program can be maintained.\n Self-management programs should be considered for people from culturally and linguistically diverse backgrounds. Care also needs to be taken in designing recruitment strategies to minimize withdrawal rates and to ensure harder to reach people are given encouragement to participate." ]	We found some, albeit very limited, indications that in certain cases mobile phone messaging interventions may provide benefit in supporting the self-management of long-term illnesses. However, there are significant information gaps regarding the long-term effects, acceptability, costs, and risks of such interventions. Given the enthusiasm with which so-called mHealth interventions are currently being implemented, further research into these issues is needed.
CD005321	[ "15088306", "10509850", "8689457", "9663358", "14760806", "12127830", "16206349", "7794044", "15045624", "8403580", "12867587", "15487709", "15331394", "12571845", "15262244", "12421996", "15527668", "12918884", "17303443", "12428824", "12410458", "10088770", "15895892", "15703953", "8064733", "10461471", "8886085", "3063436", "16242361", "15599642", "16331769", "12851342", "10378713", "16324409", "21174485", "8689462", "8173852", "10990236", "8774159", "14760802", "10422923", "8523357", "12202120", "15776267" ]	[ "A double blind, randomized, multicenter, parallel group study of the effectiveness and tolerance of intraarticular hyaluronan in osteoarthritis of the knee.", "The role of elastoviscosity in the efficacy of viscosupplementation for osteoarthritis of the knee: a comparison of hylan G-F 20 and a lower-molecular-weight hyaluronan.", "The role of viscosupplementation with hylan G-F 20 (Synvisc) in the treatment of osteoarthritis of the knee: a Canadian multicenter trial comparing hylan G-F 20 alone, hylan G-F 20 with non-steroidal anti-inflammatory drugs (NSAIDs) and NSAIDs alone.", "Viscosupplementation with hylan G-F 20: a 26-week controlled trial of efficacy and safety in the osteoarthritic knee.", "A randomized, single-blind comparison of the efficacy and tolerability of hylan G-F 20 and triamcinolone hexacetonide in patients with osteoarthritis of the knee.", "A prospective, randomized, pragmatic, health outcomes trial evaluating the incorporation of hylan G-F 20 into the treatment paradigm for patients with knee osteoarthritis (Part 1 of 2): clinical results.", "Clinical effects of intraarticular injection of high molecular weight hyaluronan (Orthovisc) in osteoarthritis of the knee: a randomized, controlled, multicenter trial.", "Intra-articular triamcinolone hexacetonide in knee osteoarthritis: factors influencing the clinical response.", "Intra-articular steroids in knee osteoarthritis: a comparative study of triamcinolone hexacetonide and methylprednisolone acetate.", "Intra-articular treatment with hyaluronic acid in osteoarthritis of the knee joint: a controlled clinical trial versus mucopolysaccharide polysulfuric acid ester.", "A randomized placebo-controlled trial of arthroscopic lavage versus lavage plus intra-articular corticosteroids in the management of symptomatic osteoarthritis of the knee.", "Effects of different hyaluronic acid products on synovial fluid levels of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in knee osteoarthritis.", "Evaluation of the symptomatic and structural efficacy of a new hyaluronic acid compound, NRD101, in comparison with diacerein and placebo in a 1 year randomised controlled study in symptomatic knee osteoarthritis.", "Safety and efficacy of long-term intraarticular steroid injections in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled trial.", "Efficacy and safety of a single intra-articular injection of non-animal stabilized hyaluronic acid (NASHA) in patients with osteoarthritis of the knee.", "Comparison of two hyaluronan drugs and placebo in patients with knee osteoarthritis. A controlled, randomized, double-blind, parallel-design multicentre study.", "Supplementation of a home-based exercise programme with a class-based programme for people with osteoarthritis of the knees: a randomised controlled trial and health economic analysis.", "A one-year, randomised, placebo (saline) controlled clinical trial of 500-730 kDa sodium hyaluronate (Hyalgan) on the radiological change in osteoarthritis of the knee.", "A 3-month, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of a highly optimized, capacitively coupled, pulsed electrical stimulator in patients with osteoarthritis of the knee.", "Does four weeks of TENS and/or isometric exercise produce cumulative reduction of osteoarthritic knee pain?", "[Cross-linked hyaluronic acid in the treatment of osteoarthritis of the knee--results of a prospective randomized trial].", "Effects of joint lavage and steroid injection in patients with osteoarthritis of the knee: results of a multicenter, randomized, controlled trial.", "Comparison of two hyaluronan drugs in patients with advanced osteoarthritis of the knee. A prospective, randomized, double-blind study with long term follow-up.", "The safety and efficacy of intraarticular hyaluronan with/without corticosteroid in knee osteoarthritis: 1-year, single-blind, randomized study.", "A randomized, double blind, placebo controlled trial of intravenous loading with S-adenosylmethionine (SAM) followed by oral SAM therapy in patients with knee osteoarthritis.", "Hyaluronic acid in the treatment of osteoarthritis of the knee.", "High molecular weight sodium hyaluronate (hyalectin) in osteoarthritis of the knee: a 1 year placebo-controlled trial.", "Clinical trial of intra-articular injection of sodium hyaluronate in patients with osteoarthritis of the knee.", "A double-blind randomized controlled trial comparing alternate forms of high molecular weight hyaluronan for the treatment of osteoarthritis of the knee.", "Hylan G-F 20 efficacy on articular cartilage quality in patients with knee osteoarthritis: clinical and MRI assessment.", "Efficacy of topical diclofenac diethylamine gel in osteoarthritis of the knee.", "Corticosteroid compared with hyaluronic acid injections for the treatment of osteoarthritis of the knee. A prospective, randomized trial.", "A randomized trial of acupuncture as an adjunctive therapy in osteoarthritis of the knee.", "[A multi-central, randomized, controlled clinical trial of glucosamine hydrochloride/sulfate in the treatment of knee osteoarthritis].", "Safety and efficacy of topical diclofenac sodium gel for knee osteoarthritis in elderly and younger patients: pooled data from three randomized, double-blind, parallel-group, placebo-controlled, multicentre trials.", "Intra-articular hyaluronic acid compared to intra-articular triamcinolone hexacetonide in inflammatory knee osteoarthritis.", "A randomized controlled study of post-injection rest following intra-articular steroid therapy for knee synovitis.", "Home based exercise therapy for older patients with knee osteoarthritis: a randomized clinical trial.", "Intra-articular hyaluronan injections in the treatment of osteoarthritis of the knee: a randomised, double blind, placebo controlled multicentre trial. Hyaluronan Multicentre Trial Group.", "A randomized comparative study of short term response to blind injection versus sonographic-guided injection of local corticosteroids in patients with painful shoulder.", "Effects of perioperative analgesic technique on the surgical outcome and duration of rehabilitation after major knee surgery.", "The treatment of osteoarthritis of the knee with pulsed electrical stimulation.", "Efficacy of intraarticular hyaluronic acid in patients with osteoarthritis--a prospective clinical trial.", "Intra-articular hyaluranic acid compared with progressive knee exercises in osteoarthritis of the knee: a prospective randomized trial with long-term follow-up." ]	[ "To investigate the efficacy and tolerability of a course of 5 injections of hyaluronan (HA) given at intervals of one week in patients with symptomatic, mild to moderate osteoarthritis (OA) of the knee.\n A double blind, randomized, parallel group, multicenter (17 centers), saline vehicle-controlled study was conducted over 18 weeks. Patients received either 25 mg (2.5 ml) HA in a phosphate buffered solution or 2.5 ml vehicle containing only the buffer by intraarticular injection. Five injections were given at one week intervals and the patients were followed for a further 13 weeks. The Western Ontario McMaster (WOMAC) OA instrument was used as the primary efficacy variable and repeated measures analysis of covariance was used to compare the 2 treatments over Weeks 6, 10, 14, and 18.\n Of 240 patients randomized for inclusion in the study, 223 were evaluable for the modified intention to treat analysis. The active treatment and control groups were comparable for demographic details, OA history, and previous treatments. Scores for the pain and stiffness subscales of the WOMAC were modestly but significantly lower in the HA-treated group overall (Weeks 6 to 18; p < 0.05) and the statistically significant difference from the control was not apparent until after the series of injections was complete. The physical function subscale did not reach statistical significance (p = 0.064). Tolerability of the procedure was good and there were no serious adverse events that were considered to have a possible causal relationship with the study treatment.\n Intraarticular HA treatment was significantly more effective than saline vehicle in mild to moderate OA of the knee for the 13 week postinjection period of the study.", "The objective of this 12-week, double-masked, randomized, multicenter study was to compare the elastoviscous properties of a high-molecular-weight viscosupplement, hylan G-F 20 (polymer concentration, 0.8%), with those of a lower-molecular-weight hyaluronan (LMW HA) product (polymer concentration, 1%) and to determine the relationship of elastoviscosity to efficacy in the treatment of patients with osteoarthritis (OA) of the knee. Patients had radiographically confirmed primary idiopathic OA of the knee (Larsen grades I to V) with pain despite other treatments. After a 2-week washout period, 70 patients (73 knees) received three 2-mL intra-articular injections of test solution at 1-week intervals. Thirty-eight patients (38 knees) received hylan G-F 20, and 32 patients (35 knees) received LMW HA. During the 12-week follow-up period, the primary outcome measures assessed by patients (using a visual analogue scale) were weight-bearing pain, most painful knee movement, and overall treatment response; the primary outcome measures assessed by study evaluators were weight-bearing pain and overall assessment of treatment. The dynamic elastoviscous properties of the test solutions were measured on an oscillating Couette-type rheometer. Hylan G-F 20 was more elastoviscous than the LMW HA at all frequencies measured (0.001 to 10 Hz). At the final evaluation, patients who received hylan G-F 20 had significantly better results on all primary outcome measures compared with those who received LMW HA. No systemic adverse events were reported. Local adverse events consisted of pain or swelling, noted in 2 of 38 knees injected with hylan G-F 20, and pain, noted in 1 of 35 knees injected with LMW HA (adverse event rates per injection, 1.8% and 0.9%, respectively). The difference in the incidence of adverse events between groups was not statistically significant. The higher-molecular-weight, more elastoviscous hylan G-F 20 had significantly greater pain-relieving effects than did the lower-molecular-weight, less elastoviscous hyaluronan.", "To determine the safety and efficacy of viscosupplementation with hylan G-F 20, a cross-linked hyaluronan preparation, used either alone or in combination with continuous non-steroidal anti-inflammatory drug (NSAID) therapy, a randomized, controlled, multicenter clinical trial, assessed by a blinded assessor, was conducted in 102 patients with osteoarthritis (OA) of the knee. All patients were on continuous NSAID therapy for at least 30 days prior to entering the study. Patients were randomized into three parallel groups: (1) NSAID continuation plus three control arthrocenteses at weekly intervals; (2) NSAID discontinuation but with three weekly intra-articular injections of hylan G-F 20; and (3) NSAID continuation plus three injections, one every week, intra-articular injections of hylan G-F 20. Outcome measures of pain and joint function were evaluated by both the patients and an evaluator at baseline and weeks 1, 2, 3, 7 and 12, with a follow-up telephone evaluation at 26 weeks. At 12 weeks all groups showed statistically significant improvements from baseline, but did not differ from each other. A statistical test for the equivalence, the q-statistic, demonstrated that viscosupplementation with hylan G-F 20 was at least as good or better than continuous NSAID therapy for all outcome measurements except activity restriction. At 26 weeks both groups receiving hylan G-F 20 were significantly better than the group receiving NSAIDs alone. A transient local reaction was observed in three patients after hylan G-F 20 injection; only one patient withdrew from the study as a result and all recovered without any sequela. Hylan G-F 20 is a safe and effective treatment for OA of the knee and can be used either as a replacement for or an adjunct to NSAID therapy.", "Hylan G-F 20, which is derived from hyaluronan, is a highly purified, elastoviscous fluid with rheologic properties similar to those of synovial fluid in the knee joints of healthy young persons. The efficacy and safety of viscosupplementation with hylan G-F 20 were evaluated in a multicenter, double-masked clinical study in patients with chronic idiopathic osteoarthritis (OA) of the knee of 1 to 30 years' duration. Three intra-articular injections of 2 mL hylan G-F 20 were administered 1 week apart to 57 knees. The control group (60 knees) received 2 mL of physiologic buffered saline solution at the same intervals. Patients were predominantly female (65%), with a mean age of 62 years and mean weight of 76 kg. Using a visual analogue scale, patients assessed the following clinical variables: pain during weight-bearing, pain at rest during the night, reduction of pain during the most painful movement of the knee, and treatment success. Evaluators also assessed patients' loss of activity while performing difficult daily tasks and treatment success. There was dramatic early improvement in all six variables with hylan G-F 20 beginning after the first injection; the improvement continued through the study end points. The differences between hylan G-F 20 and saline treatment were statistically significant for all outcome measures. In the hylan G-F 20 group, 39% to 56% of patients were free or nearly free of weight-bearing pain 10 to 24 weeks after the last injection. Treatment with saline was less effective, with fewer than 13% of patients free or nearly free of weight-bearing pain. Use of rescue therapy was significantly greater in the saline group than in the hylan G-F 20 group. No adverse events were observed in the injected joint after hylan G-F 20 treatment. These results demonstrate that hylan G-F 20 is effective and well tolerated in the management of chronic idiopathic OA.", "To assess prospectively the efficacy and tolerability of hylan G-F 20 (HG-F 20; Synvisc) and intraarticular triamcinolone hexacetonide (TH; Aristospan) for treatment of osteoarthritis (OA) knee pain in a 26 week, randomized, multicenter, evaluator-blind study.\n Patients with OA were treated with typical regimens of HG-F 20 (n = 113) and TH (n = 102). Primary assessments were the WOMAC question A1 (pain walking on a flat surface), and a 100 mm visual analog scale (VAS) for patient and investigator overall assessments. Total WOMAC and WOMAC domain C (function) scores were also assessed. The intent-to-treat population was analyzed using a last-observation carried forward approach.\n Maximum pain relief occurred at 1-2 weeks for TH and at Week 12 for HG-F 20. At Weeks 12 and 26, HG-F 20 was significantly better than TH for the WOMAC question A1 responses (p = 0.0071 and p = 0.0129, respectively), and patient VAS (p < 0.0001 and p < 0.0001) and investigator VAS (p < 0.0300 and p = 0.0004) assessments. Similar significant (p < 0.01) results were observed at Weeks 12 and 26 for total WOMAC and domain C scores. While 15 TH-treated patients discontinued the study due to lack of efficacy, none did so with HG-F 20 treatment (p < 0.01). Both agents were well tolerated with similar adverse event profiles.\n Viscosupplementation with HG-F 20 resulted in a longer duration of effect than TH with a comparable tolerability profile. These data support the preferential use of HG-F 20 over TH for treatment of chronic OA knee pain.", "First, to assess the clinical effectiveness of hylan G-F 20 in an appropriate care treatment regimen (as defined by the American College of Rheumatology (ACR) 1995 guidelines) as measured by validated disease-specific outcomes and health-related quality of life endpoints for patients with osteoarthritis (OA) of the knee. Second, to utilize the measures of effectiveness and costs in an economic evaluation (see accompanying manuscript).\n A total of 255 patients with OA of the knee were enrolled by rheumatologists or orthopedic surgeons into a prospective, randomized, open-label, 1-year, multi-centred trial, conducted in Canada. Patients were randomized to 'Appropriate care with hylan G-F 20' (AC+H) or 'Appropriate care without hylan G-F 20' (AC). Data were collected at clinic visits (baseline, 12 months) and by telephone (1, 2, 4, 6, 8, 10, and 12 months).\n The AC+H group was superior to the AC group for all primary (% reduction in mean Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scale: 38% vs 13%,P =0.0001) and secondary effectiveness outcome measures. These differences were all statistically significant and exceeded the 20% difference between groups set a priori by the investigators as the minimum clinically important difference. Health-related quality of life improvements in the AC+H group were statistically superior for the WOMAC pain, stiffness and physical function (all P< 0.0001), the SF-36 aggregate physical component (P< 0.0001) and the Health Utilities Index Mark 3 (HUI3) overall health utility score (P< 0.0001). Safety (adverse events and patient global assessments of side effects) differences favoured the AC+H group.\n The data presented here indicate that the provision to patients with knee OA of viscosupplementation with hylan G-F 20 within an appropriate care treatment regimen provides benefits in the knee, overall health and health related quality of life at reduced levels of co-therapy and systemic adverse reactions.\n Copyright 2002 OsteoArthritis Research Society International. Published by Elsevier Science Ltd. All rights reserved.", "To evaluate the efficacy and safety of injection of high molecular weight (HMW) hyaluronan (Orthovisc) in patients with mild, moderate, and severe knee osteoarthritis (OA).\n A randomized, arthrocentesis-controlled, multicenter trial. Patients (n = 372) were randomized to 4 weekly HMW hyaluronan injections (O4, n = 128), 3 weekly HMW hyaluronan injections followed by one arthrocentesis (O3A1, n = 120), or 4 arthrocenteses without injection (control group, A4, n = 124). All patients had knee OA, as determined by Kellgren-Lawrence (K-L) grade, and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain score > or = 200 mm and < 400 mm in index knee and < 150 mm in contralateral knee. The primary outcome measure was the proportion of patients achieving a 20% relative and 50 mm absolute improvement from baseline in WOMAC pain score at Weeks 8, 12, 16, and 22 post-baseline in the index knee. Secondary outcomes were Patient Global score, Investigator Global score, and Pain on Standing score.\n The evaluable subgroup consisted of patients with K-L grade 2 or 3 at baseline. The comparison of O4 versus A4 for the primary outcome approached, but did not reach, significance in the evaluable subgroup: 76% of O4 patients had > or = 20% improvement in WOMAC pain score at Week 8 compared to 62% of A4 patients. More O4 patients had > or = 40% improvement in WOMAC pain score compared to A4. The effectiveness of the 3-injection regimen (O3A1) was masked by a possible placebo effect from the needle injection procedure in the A4 (control) group. No differences between groups were observed with respect to incidence of adverse events.\n Our findings indicate that HMW hyaluronan is safe and seems to be effective in the treatment of mild to severe OA of the knee.", "To assess the efficacy of a single intra-articular injection of triamcinolone hexacetonide (THA) in knee osteoarthritis (OA) and examine factors which may relate to treatment efficacy.\n Eighty four patients with clinical and radiographic evidence of knee OA were recruited and randomly allocated to receive either THA (20 mg in 1 ml) or placebo (0.9% normal saline, 1 ml). Follow up assessments evaluated the following outcome variables: patient opinion of overall change in the treated knee, visual analogue pain score (VAS), distance walked in one minute (WD), and Health Assessment Questionnaire modified for lower limb function (HAQ).\n Seventy eight percent of THA and 49% of placebo treated patients reported overall improvement at week 1 (p < 0.05). At week 6, improvement was reported in 57% and 55% of patient groups, respectively. VAS improved in both groups at week 1 (THA, p < 0.001; placebo, p < 0.05) and week 6 (both p < 0.01). Improvement in VAS was significantly greater among THA treated patients at week 1 only (p < 0.01). Subgroup analysis of THA treated patients revealed greater improvement in VAS among patients with clinical evidence of an effusion (p < 0.05), and those who had synovial fluid successfully aspirated at the time of injection (p < 0.01). WD improved in THA treated patients at week 1 (p < 0.001), and in both groups at week 6 (THA, p < 0.001; placebo, p < 0.01). Improvements in HAQ were seen in THA patients only at weeks 1 and 6 (p < 0.05). Regression analysis did not identify any additional clinical, radiographic, or synovial fluid characteristics which influenced the response.\n THA provided short term pain relief in knee OA. Increased benefit was associated with both clinical evidence of joint effusion and successful aspiration of synovial fluid at the time of injection.", "The aim of this study was to compare the effectiveness of triamcinolone hexacetonide (THA) and methylprednisolone acetate (MPA), given via the intra-articular route at equipotent dosage to patients with symptomatic knee OA with effusion, in a double-blind randomized comparative trial. Consecutive hospital-referred patients who fulfilled the American College of Rheumatology criteria for knee OA (clinical and radiographic) were randomly allocated to receive either THA 20 mg (1 ml) or MPA 40 mg (1 ml). All patients had synovial fluid aspirated from their knee joint at the time of injection. Assessments were made at 0, 3 and 8 weeks by a second operator, thus blinding both patient and assessor. Outcomes measured at each visit were: knee pain in the previous 48 h (expressed on a 100 mm visual analog scale; VAS), stair climb time (SCT) and Lequesne index score (LEQ). Changes in VAS, SCT and LEQ were compared between the groups using a Student's paired t test. Fifty-seven patients were studied (44 female, 13 male) with a mean age of 62.5 years. Both steroids gave significant pain relief (VAS) at week 3 ( p<0.01) but only MPA showed an effect on VAS and LEQ scores at week 8 compared to baseline ( p<0.05). THA was more effective than MPA at pain reduction at week 3 ( p<0.01); this difference was lost at week 8 ( p=0.17). There was no significant difference between the two drugs in functional endpoints (SCT, LEQ) at either 3 or 8 weeks. Both THA and MPA offer at least temporary symptomatic benefit in knee OA. THA is more effective than MPA at week 3, but its effect is lost by week 8. MPA still has an effect at week 8.", "In a single-blind, randomized clinical trial, both the efficacy and safety of hyaluronic acid (HA) were compared with that of mucopolysaccharide polysulfuric acid ester (MPA) in patients with osteoarthritis of the knee joint. Both agents were administered intra-articularly over six weeks. Patients received either seven injections of HA or 13 injections of MPA. Joint function, range of motion, severity of pain, the general condition of the bony structure and soft tissue of the joint area, and the global clinical efficacy and safety of the medication were assessed. The mean improvement in the modified total Larson rating score was 22% (SD = 28) after HA treatment and 7% (SD = 17) after treatment with MPA (analysis of variance: p = 0.02). This change was mainly caused by a reduction of pain. The onset of pain relief was more rapid in the HA group. The therapeutic effect increased in both treatment groups during the follow-up period. During this interval, lasting six months after the start of treatment, a further reduction of pain and an improvement of knee joint function could be observed. At the end of the study, 25 out of 33 (76%) patients in the HA group and 11 out of 24 (46%) patients in the MPA group were symptom-free or markedly improved (Chi-square test: p = 0.02). Both agents were tolerated very well.", "To assess the efficacy of intra-articular steroid injections following arthroscopy and joint lavage in symptomatic OA of the knee.\n Seventy-seven patients with OA of the knee were randomized to receive either 120 mg methylprednisolone acetate (MPA) or placebo following arthroscopy. Clinical assessments included severity of pain on movement and at rest, stiffness, the presence of joint effusions, range of movement, WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score and Lequesne functional assessment. The outcome measures were evaluated at baseline and 2, 4, 8, 12 and 24 weeks. Further arthroscopies and synovial biopsies were performed at the time of clinical response and at relapse.\n An intention-to-treat analysis was performed on 71 patients (38 MPA, 33 placebo). Using the OARSI (Osteoarthritis Research Society International) response criteria, 58% of the steroid group vs 33% of the placebo group (adjusted relative risk = 2.38) (P = 0.004) responded at 4 weeks. At other time points, there were no significant differences between the treatment groups. There were no significant differences between the two treatment groups for pain, stiffness or WOMAC or Lequesne assessments at any time point.\n The response to intra-articular corticosteroids following joint lavage is short-lived (2-4 weeks), achievement of an OARSI response criterion being the only difference between the two groups.", "The aim of this study was to evaluate the effects of different hyaluronic acid (HA) forms on synovial fluid levels of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) during the treatment of patients with knee osteoarthritis (OA). Forty patients were randomly assigned to 2 groups that were treated with native sodium hyaluronate (group I) or cross-linked hylan G-F 20 (group II). Clinical evaluations and synovial fluid aspirations were performed before the 1st injection (baseline), the 2nd injection (week 1), the 3rd injection (week 2), and at 1 week after the 3rd injection (week 3). Synovial fluid levels of both ICAM-1 and VCAM-1 were significantly reduced at weeks 1 to 3, compared to the baseline values. The Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index was used for clinical evaluations; the WOMAC pain score and physical function score were progressively improved at weeks 1 to 3 in both groups; the WOMAC stiffness score was significantly improved at week 3 in both groups. No significant differences were noted between the 2 treatment groups in respect to ICAM-1 levels, VCAM-1 levels, WOMAC pain score, stiffness score, or physical function score at any time. The decreased ICAM-1 and VCAM-1 levels after intra-articular HA injection may help to explain the anti-inflammatory effects of HA therapy in knee OA.", "To evaluate long term efficacy of three iterative courses of three weekly intra-articular (IA) injections of NRD101 in the treatment of symptomatic knee osteoarthritis (OA).\n A 1 year prospective, multicentre, randomised, double blind, placebo controlled study of 301 patients aged >50 years with painful and radiological medial knee OA. Patients were randomly assigned into three groups receiving: (1) three courses of three IA injections of hyaluronic acid (HA) + oral placebo; (2) IA injections of saline solution + diacerein 100 mg/day; (3) IA injections of saline solution + oral placebo. Demographic data and symptomatic criteria-pain, Lequesne's index, patient's global assessment of disease activity, percentage of painful days-were obtained during the study; primary structural criterion was JSW. Efficacy criteria were changes in pain VAS, joint space narrowing (JSN), and percentage of progressors (JSN >0.5 mm). An intention to treat analysis was used for symptomatic variables, and completer analysis for structural variables.\n Baseline characteristics were similar between the three groups. Mean (SD) improvement in pain VAS was clinically relevant (-33.9 (27.3), n = 301), but with no difference between the groups (p = 0.96). JSW deteriorated (-0.09 (0.55) mm, n = 277, p = 0.01), but with no difference between the groups (p = 0.82). Percentages of progressors were 17.7, 18.9, and 20.3% (p = 0.90), in groups 1, 2, and 3, respectively.\n A weak but statistically significant structural deterioration occurred over 1 year, together with clinically relevant symptomatic improvement in patients receiving oral drug and iterative IA injections. Symptomatic and/or structural effects for both this new HA compound and diacerein were not demonstrated.", "To evaluate the safety and efficacy of long-term intraarticular (IA) steroid injections for knee pain related to osteoarthritis (OA).\n In a randomized, double-blind trial, 68 patients with OA of the knee received IA injections of triamcinolone acetonide 40 mg (34 patients) or saline (34 patients) into the study knee every 3 months for up to 2 years. The primary outcome variable was radiologic progression of joint space narrowing of the injected knee after 2 years. Measurements of minimum joint space width were performed by an automated computerized method on standardized fluoroscopically guided radiographs taken with the patient standing and with the knee in a semiflexed position. The clinical efficacy measure of primary interest was the pain subscale from the Western Ontario and McMaster Universities OA Index (WOMAC). Efficacy measures of secondary interest were the total score on the WOMAC, physician's global assessment, patient's global assessment, patient's assessment of pain, range of motion (ROM) of the affected knee, and 50-foot walking time. Clinical symptoms were assessed just before each injection.\n At the 1-year and 2-year followup evaluations, no difference was noted between the two treatment groups with respect to loss of joint space over time. The steroid-injected knees showed a trend toward greater symptom improvement, especially at 1 year, for the WOMAC pain subscale, night pain, and ROM values (P = 0.05) compared with the saline-injected knees. Using area under the curve analyses, knee pain and stiffness were significantly improved throughout the 2-year study by repeated injections of triamcinolone acetonide, but not saline (P < 0.05).\n Our findings support the long-term safety of IA steroid injections for patients with symptomatic knee OA. No deleterious effects of the long-term administration of IA steroids on the anatomical structure of the knee were noted. Moreover, long-term treatment of knee OA with repeated steroid injections appears to be clinically effective for the relief of symptoms of the disease.", "Non-animal stabilized hyaluronic acid (NASHA) is a novel hyaluronan (HA) preparation with a 4-week intra-articular half-life. This study compared the efficacy of a single injection of NASHA with placebo in patients with osteoarthritis (OA) of the knee.\n This was a 26-week randomized, double-blind, multicenter study of a single intra-articular knee injection with either NASHA or placebo (saline). Assessments included the Western Ontario McMasters Universities osteoarthritis index (WOMAC, Likert Scale) and patients' overall global disease status. A positive response was defined as a reduction in WOMAC pain score for the study knee of 40% from baseline with a minimum improvement of > or =5 points.\n A total of 346 (NASHA 172; placebo 174) patients were treated. WOMAC scores and quality of life were improved in both the NASHA and placebo groups. For the overall population, there were no statistically significant between-group differences in response rates for any efficacy parameters. In patients with OA confined to the knee (N=216), a greater response to NASHA than placebo was observed at week 6 (P=0.025). There were few treatment-related events.\n NASHA was not superior to placebo for the primary efficacy analysis. However, these data may be confounded by the inclusion of patients with OA at other sites, as significant benefits over placebo were found among patients with OA confined to the knee. Future trials of OA that examine a local therapy might need to consider restricting the study population to those patients having OA of only the signal joint.", "To compare the efficacy and safety of intra-articular injections of two different hyaluronan preparations and placebo in patients with knee osteoarthritis.\n In a randomized, patient- and observer-blind, placebo-controlled and multicentre trial with parallel groups, 210 patients, aged 60 yr or above, with knee osteoarthritis were included in a per protocol analysis. The patients were treated with three injections, once weekly, of either native high-molecular-weight hyaluronan (Artzal((R))) or cross-linked hyaluronan (Synvisc((R))) or with placebo and were followed for 52 weeks. The primary efficacy measures were weight-bearing pain during study weeks 0-26 and the duration of clinical benefit measured with Kaplan-Meier survival analysis for weeks 0-52. The secondary outcome measures were resting and maximum pain, Lequesne index, WOMAC (Western Ontario and McMaster University Osteoarthritis Index) and SF-36 (Medical Outcomes Study Short Form Health Survey) scores.\n The intra-articular injections produced a significant reduction in weight-bearing pain, resting pain, maximum pain and Lequesne and WOMAC scores after 26 weeks. There were no significant differences in outcome between any of the three study groups during the first 26 weeks. In direct comparison against placebo for weeks 0-52, neither hyaluronan treatment (Artzal or Synvisc) showed a significantly longer duration of clinical benefit than placebo. However, when data for the two hyaluronan-treated groups were pooled, treatment with hyaluronan had a significantly longer duration of benefit compared with placebo (P = 0.047).\n Patients with knee osteoarthritis who were treated by injection into the knee of either of two hyaluronan preparations or placebo showed clinical improvement during the first 26 weeks of treatment, though neither hyaluronan preparation gave a longer duration of clinical benefit than placebo. However, when data for the two hyaluronan treatments were pooled, there was a significantly longer duration of clinical benefit for hyaluronan treatment than for placebo.", "To establish the relative effectiveness and cost of providing a home-based exercise programme versus home-based exercise supplemented with an 8-week class-based exercise programme.\n The trial was a pragmatic, single-blind randomised clinical trial accompanied by a full economic evaluation.\n Patients were randomly allocated to either home-based exercise or home exercise supplemented with class exercise programmes.\n A total of 214 patients, meeting the American College of Rheumatology's classification of knee osteoarthritis, were selected from referrals from the primary and secondary care settings.\n Both groups were given a home exercise programme aimed at increasing lower limb strength, and endurance, and improving balance. The supplemented group also attended 8 weeks of twice-weekly knee classes run by a physiotherapist. Classes represented typical knee class provision in the UK.\n Assessments of locomotor function, using a timed score of three locomotor activities, walking pain and self-reported disability with the Western Ontario and McMaster's Universities osteoarthritis index (WOMAC) were made. General health, lower limb strength, range of movement and compliance with exercise were also measured. Patients were assessed before and after treatment, and also at 6- and 12-month follow-ups. The economic evaluation looked at health service resource use and assessed cost-effectiveness by relating differential costs to differences in quality-adjusted life-years (QALYs) based on patients' responses to the EuroQol-5 Dimensions. Data were obtained at baseline, 1 month, 6 months and 12 months through face-to-face interviews and, where appropriate, examination of hospital medical records.\n Patients from the supplemented group demonstrated significantly greater improvement in locomotor function and decrease in pain while walking at all follow-ups. The supplemented group also demonstrated smaller but significant improvements in balance, strength, WOMAC score, and the physical function and pain dimensions of the Short Form-36. However, not all of these improvements were maintained over the 12-month follow-up period. There was no evidence that compliance with the home exercise programme was different or that total costs or mean QALY gains were significantly different between the groups. However, costs were slightly lower and QALY gains slightly higher in the group with the supplementary class-based programme. The economic evaluation suggests that supplemented programmes are likely to be considered cost-effective, although there is uncertainty around this estimate, with approximately 30--35% probability that the intervention would not be cost-effective.\n The supplementation of a home-based exercise programme with a class-based exercise programme led to superior improvement in the supplemented group. These differential improvements were still evident at review 12 months after treatment had ceased. The additional cost of the supplemented group was offset by reductions in resource use elsewhere in the system. Compliance with the home exercise programme did not differ between the groups. Based on this evidence, the supplementation of a home-based exercise programme with an 8-week class-based exercise programme can be confidently expected to produce small improvements in locomotor function and clinically important reductions in pain. It is recommended that future research investigates methods of increasing compliance with home exercise programmes and evaluates the impact of these interventions in the primary care setting, where most patients with knee osteoarthritis are managed.", "The primary objective of this study was to investigate structural changes, as measured by joint space narrowing (JSN), within the knee joint during treatment with intra-articular sodium hyaluronate (HA) of molecular weight 500-730 kDa in patients with osteoarthritis (OA) of the knee. Patients received a weekly intra-articular injection of either 20 mg2/ml HA or a 2 ml vehicle placebo (saline) for three weeks. This course was repeated twice more at four-monthly intervals. Concomitant treatment with analgesics or NSAIDs was allowed. The primary efficacy measure was the reduction in mean joint space width (JSW) of the medial compartment at 52 weeks. A total of 408 patients were randomised and 319 completed the one-year study (HA: n=160, placebo: n=159); 273 of the 319 were included in the primary analysis. Analysis of variance on these 273 patients did not show a statistically significant difference between the two treatment groups. However, there was a significant difference in response to treatment in terms of the baseline JSW (p=0.01), indicating that outcome of treatment may depend on-baseline JSW. Therefore, a subgroup analysis by baseline JSW was conducted. This compared patients with a JSW >4.6 mm with those with a JSW <4.6 mm. In those with radiologically milder disease at baseline and receiving HA, the JSN was significantly reduced compared with placebo (p=0.02). In patients with radiologically more severe disease there was no difference in JSN between the two treatments. Although, in this one-year study, no overall treatment effect was seen, those with radiologically milder disease at baseline had less progression of joint space narrowing when treated with HA.", "To investigate the efficacy and safety of a capacitively coupled, pulsed electrical stimulation device in treating knee osteoarthritis (OA).\n Fifty-eight outpatients with moderate to severe OA of the knee entered a 3-month, double-blind, placebo-controlled trial, using either an active or placebo device at home for 6 to 14 h/day. Outcome measures included a patient global evaluation, a patient report of knee pain severity, and the Western Ontario and McMaster Universities (WOMAC) questionnaire.\n Active treatment provided superior outcomes between baseline and 3-month follow-up measurements: 50.6% greater improvement than placebo in patient global (P=0.03), 31.2% in patient pain (P=0.04), 25.1% in WOMAC stiffness (P=0.03), 29.5% in WOMAC function (P=0.01), 19.9% in WOMAC pain (P=0.11), and 27% in total WOMAC (P=0.01). The percent of patients who improved by more than 50% was 38.5 active vs 5.3 placebo in patient global (P=0.01), 43.6 vs 15.8 in patient pain (P=0.04), 38.5 vs 10.5 in WOMAC pain (P=0.03), 28.2 vs 5.3 in WOMAC stiffness (P=0.08), 23.1 vs 5.3 in WOMAC function (P=0.14), and 23.1 vs 5.3 in total WOMAC (P=0.14). Twenty-one percent of placebo and 18% of actively treated patients developed a transient rash at the electrode sites. No other adverse device effects were reported.\n A highly optimized, capacitively coupled, pulsed electrical stimulus device significantly improved symptoms and function in knee OA without causing any serious side effects.", "To evaluate the cumulative effect of repeated transcutaneous electrical nerve stimulation (TENS) on chronic osteoarthritic (OA) knee pain over a four-week treatment period, comparing it to that of placebo stimulation and exercise training given alone or in combination with TENS.\n Sixty-two patients, aged 50-75, were stratified according to age, gender and body mass ratio before being randomly assigned to four groups.\n Patients received either (1) 60 minutes of TENS, (2) 60 minutes of placebo stimulation, (3) isometric exercise training, or (4) TENS and exercise (TENS & Ex) five days a week for four weeks.\n Visual analogue scale (VAS) was used to measure knee pain intensity before and after each treatment session over a four-week period, and at the four-week follow-up session.\n Repeated measures ANOVA showed a significant cumulative reduction in the VAS scores across the four treatment sessions (session 1, 10, 20 and the follow-up) in the TENS group (45.9% by session 20, p < 0.001) and the placebo group (43.3% by session 20, p = 0.034). However, linear regression of the daily recordings of the VAS indicated that the slope in the TENS group (slope = -2.415, r = 0.943) was similar to the exercise group (slope = -2.625, r = 0.935), which were steeper than the other two groups. Note that the reduction of OA knee pain was maintained in the TENS group and the TENS & Ex group at the four-week follow-up session, but not in the other two groups.\n The four treatment protocols did not show significant between-group difference over the study period. It was interesting to note that isometric exercise training of the quadriceps alone also reduced knee pain towards the end of the treatment period.", "The objective of this trial was to compare the effectiveness of intraarticular injection of highly cross-linked hyaluronic acid (HA) with intraarticular injection of gaseous oxygen (O 2 ) in patients with clinical symptoms of cartilage damage in the knee.\n Based on arthroscopically verified diagnosis, 111 patients were randomised and treated prospectively either with HA or O 2. The treatment was completed with an exercise program. The follow up was one year. 109 patients (56 x HA, 53 x O 2 ) were statistically calculated with the Wilcoxon-test according to the results of the Lysholm-score, the Tegner-activity-index, the Womac-score for pain, stiffness, function and the VAS for pain in rest and under strain.\n Both treatments were able to attain a statistically significant reduction of pain (VAS in rest and under strain, Womac part A), a reduction of joint stiffness (Womac part B) and improvement of joint function (Womac part C, Lysholm-score) during the follow up of one year. The Tegner-activity-index showed no significant change under both treatments. The comparison of both treatments showed differences in VAS under strain (p = 0.001), the Lysholm-score (p = 0.003), Womac part A (p = 0.003) and part C (p = 0.001). As a result HA showed significant better improvements with the VAS and Lysholm-score and oxygen showed significant better changes in the Womac-score part A and C. The results with cartilage damage 2 degrees were the same as in the total (VAS strain: p = 0.029 for O 2, Lysholm-score: p = 0.003 for HA, WOMAC part A: p = 0.009 for HA, Womac part C: p = 0.006 for O 2 ). The results with cartilage damage 3 degrees showed significant differences in reduction of joint stiffness (Womac part B: p = 0.012) for O 2. For cartilage damage 4 degrees HA showed significant reduction of pain (VAS rest: p = 0.001, VAS strain: p = 0.003) and O 2 significant reduction of pain and function (Womac part A: p = 0.004, part C: p = 0.002).\n Both methods are suitable to improve significantly the discomfort due one year to osteoarthritis. The pain relief by HA and the improvement of joint function by O 2 treatment have been shown for higher degrees of cartilage damage.", "To evaluate the efficacy of joint lavage and intraarticular steroid injection, alone and in combination, in the treatment of patients with symptomatic knee osteoarthritis (OA).\n Ninety-eight patients with painful tibiofemoral OA were enrolled in a prospective, randomized, controlled, 2 x 2 factorial-design trial of 6 months' duration. The 4 treatment groups consisted of 1) intraarticular placebo (1.5 ml of 0.9% normal saline), 2) intraarticular corticosteroids (3.75 mg of cortivazol in 1.5 ml), 3) joint lavage and intraarticular placebo, and 4) joint lavage and intraarticular corticosteroid. Outcome measures evaluated at baseline, week 1, week 4, week 12, and week 24 included severity of pain (100-mm visual analog scale [VAS]), global status (100-mm VAS), and Lequesne's functional index.\n No interaction between steroid injection and joint lavage was demonstrated. Patients who had undergone joint lavage had significantly improved pain VAS scores at week 24 (P = 0.020). In contrast, corticosteroid injection had no long-term effect (P = 0.313); corticosteroid injection was associated with a decrease in pain only at week 1 (P = 0.003) and week 4 (P = 0.020). After week 4, Lequesne's functional index was not significantly improved regardless of the assigned treatment.\n Compared with placebo, both treatments significantly relieved pain but did not improve functional impairment. The effects of the 2 treatments were additive. Cortivazol provided short-term relief of pain (up to week 4). The effects of joint lavage persisted up to week 24.", "To compare the long-term effects of high and low molecular weight hyaluronic acid (HA) applications in severe (Kellgren Lawrence stage III) osteoarthritis (OA) of the knee.\n In a prospective clinical trial 184 knees (92 patients) with radiographic Kellgren Lawrence stage III OA were randomized to receive either 3 intra-articular high molecular weight HA (Hylan G-F 20) injections or 3 low molecular weight HA (Orthovisc) injections at one-week intervals. Patients were evaluated by the Hospital for Special Surgery (HSS) Knee Score and were followed-up for 12 months.\n The total HSS score in high molecular weight HA patients improved from 71.8+/-11.6 to 86.7+/-11.6 and in low molecular weight HA patients from 66.7+/-11.0 to 86.6+/-9.1 at the end of the trial (p < 0.01). There were no statistically significant differences between the groups and both had improved in all parameters at the latest follow-up (p = 0.000).\n Three intra-articular injections at intervals of 1 week of both HA preparations resulted in a pronounced reduction in pain and improved function as measured by the HSS score during a period of 52 weeks, without complications.", "The goal of this study was to assess the safety and efficacy of hyaluronan (HA) with/without corticosteroid in patients with knee osteoarthritis (OA). In a 1-year, randomized, single-blind trial, 24 patients were treated with HA weekly for 3 weeks, then three injections on the 6th month for a total of six injections. Sixteen patients were treated the same but with the addition of 1 ml triamcinolone acetonide prior to the first and fourth HA injection. The treatment was repeated at the sixth month. The patients were evaluated with the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and the visual analog pain scale (VAS). After 1 year, progression of OA was evaluated with magnetic resonance imaging (MRI). During the study, pain relief was marked in patients who received combined treatment with respect to WOMAC pain and VAS (p<0.05). At the first year, no progression was observed in either treatment group. Although all patients had improvement for both pain and function, HA together with corticosteroid was superior to HA alone for early pain relief. The MRI findings showed that neither treatment showed a progression on the damage of the cartilage.", "We evaluated the effectiveness and rapidity of onset of S-adenosylmethionine (SAM), administered as daily intravenous boluses of 400 mg for 5 days, followed by oral tablets, 200 mg thrice daily for 23 days, versus a matching placebo regimen, in the treatment of 81 patients with symptomatic knee osteoarthritis (OA).\n The study was bicentric, randomized, double blinded, and placebo controlled. Patients underwent a 7-day washout of arthritis medications prior to initiation of this study treatment. Major outcome measures were the Stanford Health Assessment Questionnaire disability and pain scales, and supplemental visual analog scales for rest and walking pain.\n At one site, patients had milder OA, the baseline characteristics of the treatment groups were well matched, and the SAM treated group showed significantly greater reduction in overall pain and rest pain (p < 0.05) than the placebo treated group. At the other site, the patients had more severe OA, randomization yielded markedly different treatment groups, and the response to treatment did not differ between groups. Onset of SAM effect was seen as early as 14 days after the start of treatment.\n SAM may be an effective treatment for some patients with symptomatic knee OA, and merits further study. Intravenous loading before oral maintenance therapy may be advantageous.", "We examined the efficacy, safety and patient satisfaction of intra-articular hyaluronic acid (HA) in patients with osteoarthritis of the knee.\n One hundred patients with mild to moderate osteoarthritis of the knee entered a randomized blind-observer trial of 6 months HA vs placebo. Primary efficacy criteria were pain on walking, measured with a visual analogue scale, and the Lequesne Index.\n For pain on walking, a significant difference in favour of HA was found for completed patients at week 5, the end of the course of injections, and at month 6, the end of the study (P = 0.0087 and P = 0.0049, respectively). Further analysis using the Last Observation Carried Forward (LOCF) also showed a significant benefit favouring HA at month 6 (P = 0.0010). For the Lequesne Index, a significant difference in favour of HA was found at week 5 (P = 0.030) and at month 2 (P = 0.0431), but this was only of borderline significance at month 4 (P = 0.0528). Patients' global assessment of efficacy favoured HA at month 6 (P = 0.012). Improvement in other secondary criteria was generally superior in the HA group compared to placebo both at week 5 and month 6. Adverse events, mainly local injection site reactions, occurred in both groups with equal frequency.\n The study demonstrated that five weekly intra-articular injections of sodium hyaluronate (Hyalgan) were superior to placebo and well tolerated in patients with osteoarthritis of the knee with a symptomatic benefit which persisted for 6 months.", "Hyaluronic acid is a natural component of cartilage and is considered not only as a lubricant in joints but also as playing a physiological role in the trophic status of cartilage. Hyalectin, a selected fraction of hyaluronic acid extracted from cocks' combs, has exhibited efficacy in animal models of osteoarthritis. To assess the efficacy and tolerability of intra-articular injections of hyalectin, we conducted a prospective, randomized, placebo-controlled trial of 1 years' duration in 110 patients with painful hydarthrodial osteoarthritis of the knee. At entry and once a week for 3 weeks, aspiration of the knee effusion and intra-articular injections of either hyalectin 20 mg (H) or its vehicle (C) were performed. The vehicle acted as the control treatment. Four weeks after the last injection, the improvement was greater in the H group compared with the C group (pain: -35.5 +/- 26.4 mm vs -25.8 +/- 21.4, P = 0.03, Lequesne's functional index: -3.8 +/- 4.3 vs -2.3 +/- 3.3, P = 0.03). During the 1 year follow-up, the need to perform supplementary local therapies (joint fluid aspiration because of painful hydarthrodial episodes and/or local corticosteroid injections) was more frequent in group C (44% vs 30%, P = 0.03). Moreover, at the final visit, the physician's overall assessment of efficacy was in favor of H (77% vs 54%, P = 0.01) and the improvement in the functional index was greater in group H (-4.4 +/- 5.1 vs -2.7 +/- 4.1, P = 0.05). This study suggests that intra-articular injections of hyalectin may (1) improve clinical condition and (2) have a long-term beneficial effect in patients with osteoarthritis of the knee.", "A multi-centre randomized, double-blind, parallel-group clinical trial was carried out in 63 patients with osteoarthritis of the knee to compare the efficacy and tolerability of a course of intra-articular injections of 20 mg sodium hyaluronate with a similar course of injections of placebo. Treatment consisted of up to 11 injections over a 23-week period. Evaluation was by means of subjective symptom and activity assessments, serially during the course of treatment and also 25 weeks thereafter. Ten patients (5 of 30 on active treatment; 5 of 33 on placebo) were withdrawn prematurely. Pain on movement, assessed by visual analogue scale (VAS) showed statistically significant (p less than 0.05 to p less than 0.0001) reductions in mean scores throughout the first 11 weeks of treatment with sodium hyaluronate but smaller, non-significant, reductions with placebo treatment. The difference between treatments was significant (p less than 0.05) at 5 weeks. Pain at rest, also assessed by VAS, showed little change in mean scores with placebo but with sodium hyaluronate there was a progressive reduction which was significant (p less than 0.01) throughout the period from 5 to 23 weeks. The difference between sodium hyaluronate and placebo was significant (p less than 0.05 to p less than 0.002) at Weeks 5, 11, 15, 19 and 23. 'Activities of daily living' were assessed using a standard scale. There were small improvements with both treatments, significant at some assessments and somewhat greater with sodium hyaluronate than placebo, but there were no statistically significant differences between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)", "To compare the safety and effectiveness of a high molecular weight hyaluronan produced by biological fermentation (Bio-HA) with those of avian-derived hyaluronan that uses cross-linking to achieve high molecular weight (CL-HA).\n This was a prospective, multicenter, randomized, double-blind trial evaluating patients with confirmed osteoarthritis of the knee. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC Index) pain subscale was the primary effectiveness measure (visual analog scale). Both products were administered via three weekly injections, with follow-up evaluations at weeks 3, 6 and 12. Acetaminophen was permitted as rescue medication and quantitated by pill counts.\n Analyses were performed on the intent-to-treat population, defined as all patients receiving at least one injection. Of the 321 patients randomized to treatment, 314 patients (98%) completed the final study assessment. Improvement in the average WOMAC Index pain score was 29.8mm (-61.6%) for Bio-HA and 28.8mm (-54.9%) for CL-HA, meeting the prospective criteria for non-inferiority. For the secondary outcome measures, statistically significant differences favored Bio-HA for the number of patients requiring acetaminophen (P=0.013) and patient global satisfaction evaluations (P=0.03). Local reactions differed between the products in that 15 effusions were reported in 13 CL-HA patients (8.1%) after injection, compared to one effusion (0.6%) after Bio-HA injection (P=0.0015).\n The effectiveness of Bio-HA was not inferior to that of CL-HA. The significantly higher incidence of post-injection effusion in the CL-HA group provides a safety advantage for Bio-HA. These data suggest that Bio-HA has an improved benefit-risk profile compared with CL-HA.", "The aim of this study was to investigate the effects of intra-articular hyaluronic acid (HA) on symptoms, functional outcome, and changes in articular cartilage assessed by magnetic resonance imaging (MRI) in patients with knee osteoarthritis. Thirty patients were randomly assigned to treatment with HA (hylan G-F 20, Synvisc) or saline. The treatment group consisted of 20 patients receiving three weekly injections of HA into one or both knees (30 knees). The control group consisted of ten patients receiving three intra-articular injections of 2 ml saline at the same intervals (ten knees). To determine the effectiveness of the HA therapy, all patients were assessed prior to the injections (baseline) and after the 1st, 2nd, 3rd, and 8th weeks. Assessment comprised the following: pain at rest, at night, and on walking using a visual analogue scale (VAS); Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, stiffness, and function scores; 15-m walking time; need for analgesics; and evaluation of treatment by the patients. MRI of patellofemoral (PF) articular cartilage was also examined before and after the course of injections at the 8th week. When compared to placebo, a significant statistical difference was found in all clinical parameters. On MRI, although the difference in the PF joint cartilage quality in the HA group before and after the treatment was statistically significant (p < 0.05), this significance was not detected between the groups after the treatment (p > 0.05). After the HA injections, a significant analgesic effect was seen as early as the 3rd week continuing up to the 8th week and functional improvement was seen at the 8th week. In conclusion, intra-articular injections of HA is an effective choice of treatment in patients with knee osteoarthritis.", "To assess the efficacy and safety of topical diclofenac diethylamine gel, 1.16%, 4 g applied qid for 3 weeks to relieve the symptoms of osteoarthritis (OA) of the knee.\n Patients with OA of the knee washed out their OA medications for at least 5 drug half-lives. Patients with adequately high baseline pain scores were randomized to apply either double-blind active or placebo gel for 3 weeks. Acetaminophen (up to 2 g/day) was supplied as rescue medication. In a diary, patients recorded compliance to dosing and use of rescue medication and assessed daily pain on movement, spontaneous pain, and pain relief. At weekly site visits, patients completed the Western Ontario and McMaster (WOMAC) Osteoarthritis Index Questionnaire, which includes assessment of pain, stiffness, and physical function, and assessed pain intensity \"right now.\" At the final visit, a global assessment of treatment efficacy was completed.\n Of 238 randomized patients, 237 were included in the intent to treat efficacy analysis. Treatments differed significantly for daily pain on movement at Day 5, and continued on most days through end of study. Peak differences were achieved in the second week. On the primary outcome, average pain on movement over Days 1-14, diclofenac gel was significantly superior to placebo gel. Scores for all 3 WOMAC indices for diclofenac gel treatment were significantly superior to placebo at Weeks 2 and 3. A significant difference was achieved on pain intensity \"right now\" at all 3 weeks. At the end of the study, patients rated diclofenac gel as significantly more effective in treating the pain of OA of the knee (p = 0.03) compared to placebo. There were no safety issues concerning adverse events or laboratory values.\n Diclofenac gel was effective and safe for relief of symptoms of OA of the knee over 3 weeks of dosing.", "Although both corticosteroid and hyaluronic acid injections are widely used to palliate the symptoms of knee osteoarthritis, little research involving a comparison of the two interventions has been done. We tested the hypothesis that there are no significant differences between Hylan G-F 20 (Synvisc) and the corticosteroid betamethasone sodium phosphate-betamethasone acetate (Celestone Soluspan) in terms of pain relief or improvement in function, as determined by validated scoring instruments.\n One hundred patients with knee osteoarthritis were randomized to receive intra-articular injection of either Hylan G-F 20 or the corticosteroid, and they were followed for six months. The patients treated with Hylan G-F 20 received one course of three weekly injections. The patients treated with the corticosteroid received one injection at the time of enrollment in the study, and they could request one more injection any time during the study. An independent, blinded evaluator assessed the patients with the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), a modification of the Knee Society rating system, and the visual analog pain scale.\n Both the group treated with the corticosteroid and the group treated with Hylan G-F 20 demonstrated improvements from baseline WOMAC scores (a median decrease from 55 to 40 points and from 54 to 44 points, respectively; p < 0.01 for both). The scores according to the Knee Society system did not significantly improve for the patients who received the corticosteroid (median, 58 to 70 points; p = 0.06) or for those who received Hylan G-F 20 (median, 58 to 68 points; p = 0.15). The scores on the visual analog scale improved for patients receiving Hylan G-F 20 (median, 70 to 52 mm; p < 0.01) but not for the patients who received the corticosteroid (median, 64 to 52 mm; p = 0.28). However, no significant differences between the two treatment groups were found with respect to the WOMAC, Knee Society system, or visual analog scale results. Women demonstrated a significant improvement in only one of the six possible outcome-treatment combinations (the WOMAC scale), whereas men demonstrated significant improvements in five of the six outcomes (all measures except the Knee Society rating system).\n No differences were detected between patients treated with intra-articular injections of Hylan G-F 20 and those treated with the corticosteroid with respect to pain relief or function at six months of follow-up. Women demonstrated significantly less response to treatment than men did for both treatments on all three outcome scales. Such significant gender-related differences warrant further investigation.", "The purpose of this study was to investigate the efficacy of acupuncture as an adjunctive therapy to standard care for the relief of pain and dysfunction in elderly patients with osteoarthritis (OA) of the knee.\n Seventy-three patients with symptomatic OA of the knee were randomly assigned to treatment (acupuncture) or standard care (control). Analysis was performed on last score carried forward to account for patients who dropped out before completion. Patients self-scored Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Lequesne indices at baseline and at 4, 8 and 12 weeks. Patients in the control group were offered acupuncture treatment after 12 weeks. The data for these patients are pooled with those from the original acupuncture group for within-group analysis.\n Patients randomized to acupuncture improved on both WOMAC and Lequesne indices compared to those who received standard treatment alone. Significant differences on total WOMAC Scale were seen at 4 and 8 weeks. There appears to be a slight decline in effect at 4 weeks after cessation of treatment (12 weeks after first treatment). No adverse effects of acupuncture were reported.\n These data suggest that acupuncture is an effective and safe adjunctive therapy to conventional care for patients with OA of the knee.", "To evaluate the efficacy and safety of glucosamine hydrochloride (GH) in the treatment of patients with knee osteoarthritis (OA) comparing with glucosamine sulfate (GS).\n A multi-central, randomized, parallel-controlled clinical trial of GH vs GS was performed. 142 patients suffering from knee OA were randomized into 2 groups, treated with GH and GS for 480 mg and 500 mg one time respectively. Patients received medicine 3 times daily with total 1440 mg per day for GH group and 1500 mg for GS group, orally for 4 weeks and were assessed for drug efficacy and safety for 2 more weeks. Knee pain at rest, at movement and at pressure, knee swelling, morning stiffness and walking ability were recorded at 1, 2, 3, 4 and 6 week according to Lequesne's criteria. Other features such as therapeutic efficacy, adverse events and laboratory parameters were also recorded.\n A considerable improvement in OA symptoms and a reduce of total Lequesne's score were observed in both groups after the 4-week treatment. The Lequesne's score decreased to 3.4 +/- 1.9 (P < 0.05) and 3.4 +/- 1.8 (P < 0.05) after 4-week treatment comparing to 0-week in the GH (9.4 +/- 1.8) group and GS (9.5 +/- 1.4) group respectively. There was no significant difference between 2 groups in decreasing the Lequesne's score (P > 0.05). The symptomatic improvement rates in patients were 91.4% and 90.0% at 4-week treatment in the GH and GS group respectively (P > 0.05). There was a remnant therapeutic effect in both groups at 2 weeks after discontinuation of the treatment. And 4.2% (3/71) of patients on GH reported adverse events, vs 7.0% (5/71) adverse events with GS group (P > 0.05), mainly mild stomach discomfort and constipation.\n There were no significant differences in efficacy and safety between GH and GS groups in the treatment of knee OA. Glucosamine hydrochloride is as effective and safe as glucosamine sulfate.", "NSAIDs used for the treatment of osteoarthritis (OA) have dose-related risks for gastrointestinal, cardiovascular and renal adverse events (AEs), particularly in elderly patients. Topical NSAIDs reduce systemic NSAID exposure and may mitigate these risks.\n To evaluate the safety and efficacy of topical diclofenac sodium 1% gel (DSG) versus vehicle in patients aged 25-64 or ≥65 years who have been diagnosed with knee OA.\n Pooled data from three 12-week, randomized, double-blind, parallel-group, multicentre trials.\n US primary care, internal medicine, orthopaedic and rheumatology practices.\n Aged ≥25 years with mild to moderate (Kellgren-Lawrence grade 1-3) knee OA.\n After a 1-week analgesic washout, patients applied 4 g of DSG or vehicle four times daily to one knee. Rescue paracetamol (acetaminophen) up to 4 g/day was allowed.\n Key efficacy outcomes common to the three trials were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain (0-20) and physical function (0-68) subscales, global rating of disease (GRD; 100-mm visual analogue scale [VAS]) and pain on movement (POM; 100-mm VAS). ANOVA was used to compare efficacy outcome differences (DSG vs vehicle) by age (25-64 or ≥65 years). A flare design was used that defined a subset of patients who experienced increased pain during the washout period (modified efficacy subpopulation [MES]).\n The MES included both patients aged 25-64 (n = 602) and ≥65 (n = 374) years. Patients in each age group applied >90% of scheduled doses. Among patients aged 25-64 years, the improvement from baseline to week 12 (least squares mean [standard error]) was greater for DSG versus vehicle for WOMAC pain (-5.8 [0.3] vs -4.7 [0.3], p = 0.007), WOMAC physical function (-17.9 [0.9] vs -14.2 [0.9], p = 0.002), GRD (-29.5 [1.6] vs -23.8 [1.6], p = 0.01) and POM (-37.3 [1.8] vs -29.0 [1.8], p < 0.001). Among patients aged ≥65 years, the improvements from baseline for most efficacy outcome scores were significantly greater with DSG versus vehicle: WOMAC pain (-5.3 [0.3] vs -4.1 [0.4], p = 0.02), WOMAC physical function (-15.5 [1.1] vs -11.0 [1.1], p = 0.004) and POM (-33.7 [2.2] vs -26.4 [2.2], p = 0.02). The efficacy of DSG did not differ significantly between patients aged 25-64 years and ≥65 years: WOMAC pain (p = 0.85), WOMAC physical function (p = 0.70), GRD (p = 0.86) and POM (p = 0.81). The incidence of any AE was greater with DSG than with vehicle among patients aged 25-64 years (56.6% vs 50.8%) and ≥65 years (55.8% vs 43.9%). Treatment-related application site dermatitis was more common with DSG compared with vehicle in both younger (4.0% vs 0.7%, respectively) and older (5.8% vs 0.4%, respectively) patients and was the main reason for the difference in treatment-related AEs between the DSG and vehicle groups. Gastrointestinal AEs were infrequent among patients treated with DSG and similar to incidence rates with vehicle in both age groups.\n DSG was effective and generally well tolerated in adults regardless of age. These data support the topical application of DSG for relief of OA knee pain in elderly and younger patients. Clinicaltrials.gov registration numbers NCT00171626, NCT00171678, NCT00426621.", "The aim of this study was to determine the comparative efficacy and safety of intra-articular (i/a) triamcinolone. hexacetonide (TH) and i/a hyaluronic acid (HA) in inflammatory knee osteoarthritis. A randomized double-blind comparative trail was carried out in a rheumatology outpatient department. There were 63 patients (24 male, 39 female, mean age 70.5 years) with bilateral symptomatic knee osteoarthritis with effusion. Each was given five HA injections at weekly intervals; or 20 mg TH followed by four placebo (saline) injections. Patients were examined weekly during the treatment period and then at monthly intervals for a further 6 months. Assessment included recording of: visual analog scores (VAS) for pain; duration of stiffness; range of movement; joint effusion; local heat; synovial thickening; joint-line and periarticular tenderness. The principal outcome measure was pain on a self-selected activity assessed by Vas. The two groups were comparable at entry and no significant differences between the groups developed at any time during the treatment period. However, there was a high drop-out rate and intention to treat analysis failed to demonstrate statistically significant differences between the groups. In patients remaining in the study, significantly less pain was experienced by the HA group during the 6 month follow-up period. Other parameters showed a similar trend in favor of experienced by the HA group during the 6 month follow-up period. Other parameters showed a similar trend in favor of HA. We could not, however, demonstrate significant differences between the placebo and active treatments. HA may therefore be a useful additional therapy for symptomatic knee osteoarthritis and may have a long duration of action.", "In order to assess the effect of 24 h observed bed rest following intra-articular steroid injection of the knee joint in patients with an inflammatory arthritis such as RA, AS or colitic arthropathy, 91 patients with inflammatory arthritis of one knee joint were randomized to receive 24 h bed rest in hospital following intra-articular steroid injection or were injected in outpatients. The clinical and laboratory assessments such as pain and stiffness on a 10-cm visual analogue scale, knee circumference (cm), 50 ft walking time (s), CRP and ESR were measured before receiving the steroid injection and at 3, 6, 12 and 24 weeks. Both groups of patients improved clinically and serologically at 3 weeks. By 12 weeks the degree of improvement in the pain score, stiffness score, knee circumference, 50 ft walking time and CRP was better in the rest group and these differences persisted to 24 weeks. For each outcome variable the summary measure of response was significantly better in the rest group compared to the no rest group. Intra-articular steroid injection of the knee joint followed by strict i inpatient bed rest for 24 h results in a greater degree of clinical and serological improvement, compared to routine outpatient injections for up to 6 months. It is therefore possible that 24-h post-injection rest will result in a prolonged duration of clinical response and reduce the need for frequent steroid injections and the risk of complications.", "This 8 week randomized, double blind clinical trial compared the effect of a combined home based progressive exercise program and treatment with the nonsteroidal medication oxaprozin to treatment with oxaprozin alone on pain and physical functioning in older community dwelling patients with unilateral knee osteoarthritis (OA).\n Efficacy variables measured before and after 8 weeks included (1) pain using the Western Ontario McMaster (WOMAC) pain, physical disability, and stiffness subscales and a 10 point visual analog scale (VAS) before and after self-paced walking (SPW) and stepping (SPS) functional tasks; (2) physical function using the time to complete a self-paced 40 m walk (SPW) and 20 cycles of 2 steps (SPS): (3) physical activity level using the Physical Activity Scale for Elderly (PASE); (4) clinical measures of knee functioning (range of motion). One hundred seventy-nine men and women (mean age 74 +/- 6 yrs) with radiographic evidence of mild/moderate medial compartment OA were randomized to either a progressive home based knee exercise program (n = 88) or a control program (n = 89). All patients were given oxaprozin 1,200 mg per os daily.\n We observed significant reduction from baseline in activity related pain (VAS); and improvement in SPW and SPS test time, passive range of motion, and PASE after 8 weeks in both groups. These changes were significantly greater (p < 0.05) in the exercise versus sham group.\n Addition of a progressive exercise program to nonsteroidal antiinflammatory therapy in patients with knee OA can improve measures of activity and activity related pain more than medication alone.", "To assess the effects of intra-articular injections of hyaluronan on symptoms of knee osteoarthritis (OA).\n Two hundred and forty patients with symptomatic, radiological knee OA were randomly assigned to treatment with weekly injections for five weeks with either 25 mg of high molecular weight hyaluronan or vehicle. Results were evaluated at weeks 1, 2, 3, 4, 5, 13, and 20 by visual analogue scales (pain, function, motion, activity), algofunctional index, and global evaluation by patient and investigator. Analysis was by \"intention to treat', \"per protocol', and area under the curve principles on unstratified patient groups and for patients stratified into four groups of equal size by age and baseline algofunctional index.\n No serious side effects were reported. At 20 weeks both treatment groups were improved compared with baseline, with no difference between unstratified groups treated with placebo or hyaluronan. Comparison of treatment groups stratified by age and baseline algofunctional index revealed a significant difference in favour of hyaluronan over placebo (pain, activity, algofunctional index, global evaluations by patient and investigator) for patients older than 60 years and with a baseline algofunctional index greater than 10. There was no clinically relevant difference between the two treatments for the other three stratified subgroups of younger age or fewer symptoms. Similar results were obtained by area under the curve, intention to treat, and per protocol analysis.\n Patients older than 60 years with knee osteoarthritis and with significant symptoms corresponding to an index of severity of knee disease of 10 or more, comprise the group most likely to benefit from treatment with intra-articular hyaluronan injections.", "Local corticosteroid injections, commonly accepted by rheumatologists to be effective treating painful shoulder, have shown controversial results. High frequency ultrasonography is an accurate and safe imaging modality for guiding musculoskeletal injections. We prospectively compared the short term response to randomized blind injection versus sonographic-guided injection of local corticosteroid in patients with painful shoulder.\n We studied 41 consecutive patients with painful shoulder. Patients with previous trauma or chronic inflammatory arthritis were excluded. No patient had received previous physiotherapy or local steroid injection in the shoulder. Patients were randomized to receive either a blind subacromial injection of 20 mg triamcinolone (Group 1, n = 20) or a sonographic guided injection of 20 mg triamcinolone (Group 2, n = 21) by the same rheumatologist blinded to the clinical evaluation. In both groups we recorded shoulder abnormalities and the location of the steroid postinjection by ultrasound. Each patient was clinically assessed within 5 days before injection and 6 weeks after injection by another rheumatologist without knowledge of the injection technique performed. Clinical assessment included demographic and clinical data, a visual analog scale (VAS) for pain (0-100), the Shoulder Function Assessment (SFA) scale (0-70), and postinjection adverse effects. No patient received physical therapy during the followup period. Initially, demographic, clinical, and ultrasonographic findings in both groups showed no significant differences.\n Six weeks after injection, the VAS and the SFA score showed a significantly greater improvement in Group 2 compared with Group 1 (mean VAS score change 34.9 for Group 2 vs 7.1 for Group 1, p < 0.001; and mean SFA score change 15 for Group 2 vs 5.6 for Group 1, p = 0.012). One patient in Group 1 reported mild postinjection adverse effects.\n We suggest that sonographic-guided corticosteroid injections should be indicated, at least, in patients with poor response to previous blind injection to ensure accurate medication placement in order to improve therapeutic effectiveness.", "Continuous passive motion after major knee surgery optimizes the functional prognosis but causes severe pain. The authors tested the hypothesis that postoperative analgesic techniques influence surgical outcome and the duration of convalescence.\n Before standardized general anesthesia, 56 adult scheduled for major knee surgery were randomly assigned to one of three groups, each to receive a different postoperative analgesic technique for 72 h: continuous epidural infusion, continuous femoral block, or intravenous patient-controlled morphine (dose, 1 mg; lockout interval, 7 min; maximum dose, 30 mg/4 h). The first two techniques were performed using a solution of 1% lidocaine, 0.03 mg/ml morphine, and 2 microg/ml clonidine administered at 0.1 ml x kg(-1) x h(-1). Pain was assessed at rest and during continuous passive motion using a visual analog scale. The early postoperative maximal amplitude of knee flexion was measured during continuous passive motion at 24 h and 48 h and compared with the target levels prescribed by the surgeon. To evaluate functional outcome, the maximal amplitudes were measured again on postoperative day 5, at hospital discharge (day 7), and at 1- and 3-month follow-up examinations. When the patients left the surgical ward, they were admitted to a rehabilitation center, where their length of stay depended on prospectively determined discharge criteria\n The continuous epidural infusion and continuous femoral block groups showed significantly lower visual analog scale scores at rest and during continuous passive motion compared with the patient-controlled morphine group. The early postoperative knee mobilization levels in both continuous epidural infusion and continuous femoral block groups were significantly closer to the target levels prescribed by the surgeon than in the patient-controlled morphine group. On postoperative day 7, these values were 90 degrees (60-100 degrees)(median and 25th-75th percentiles) in the continuous epidural infusion group, 90 degrees (60-100 degrees) in the continuous femoral block group, and 80 degrees (60-100 degrees) in the patient-controlled morphine group (P < 0.05). The durations of stay in the rehabilitation center were significantly shorter: 37 days (range, 30-45 days) in the continuous epidural infusion group, 40 days (range, 31-60 days) in the continuous femoral block group, and 50 days (range, 30-80 days) in the patient-controlled morphine group (P < 0.05). Side effects were encountered more frequently in the continuous epidural infusion group.\n Regional analgesic techniques improve early rehabilitation after major knee surgery by effectively controlling pain during continuous passive motion, thereby hastening convalescence.", "The safety and effectiveness of pulsed electrical stimulation was evaluated for the treatment of osteoarthritis (OA) of the knee.\n A multicenter, double blind, randomized, placebo controlled trial that enrolled 78 patients with OA of the knee incorporated 3 primary efficacy variables of patients' pain, patients' function, and physician global evaluation of patients' condition, and 6 secondary variables that included duration of morning stiffness, range of motion, knee tenderness, joint swelling, joint circumference, and walking time. Measurements were recorded at baseline and during the 4 week treatment period.\n Patients treated with the active devices showed significantly greater improvement than the placebo group for all primary efficacy variables in comparisons of mean change from baseline to the end of treatment (p < 0.05). Improvement of > or = 50% from baseline was demonstrated in at least one primary efficacy variable in 50% of the active device group, in 2 variables in 32%, and in all 3 variables in 24%. In the placebo group improvement of > or = 50% occurred in 36% for one, 6% for 2, and 6% for 3 variables. Mean morning stiffness decreased 20 min in the active device group and increased 2 min in the placebo group (p < 0.05). No statistically significant differences were observed for tenderness, swelling, or walking time.\n The improvements in clinical measures for pain and function found in this study suggest that pulsed electrical stimulation is effective for treating OA of the knee. Studies for longterm effects are warranted.", "The goal of this study was to determine whether or not the intraarticular administration of hyaluronic acid can improve functional parameters, such as isokinetic muscle strength or total work and clinical test results in patients with osteoarthritis (OA) of the knee.\n As part of a prospective, controlled study 43 patients with osteoarthritic changes of both knees (radiographic Kellgren stage II-III) were followed in a right/left comparison. The influence of intraarticularly injected hyaluronic acid (20mg hyaluronic acid/2ml Hyalart) on functional and clinical parameters was analysed. We used the isokinetic system Cybex 600 for measuring maximal isokinetic muscle strength and total work. A total of 20 males and 23 females fulfilled the inclusion criteria with an age between 55-78 years and underwent five injections of hyaluronic acid (one injection per week). The injected knee represented the treatment group, while the contralateral knee served as the control.\n The maximum peak torque of the knee extensors in the treatment group was measured between 57+/-26.15/32.33+/-19.63Nm prior to the injections and 77.17+/-32.54/47.83+/-21.43Nm following the hyaluronic acid therapy (P< 0.01). The analysis of the knee flexors at angular velocities of 60 degrees /s and 180 degrees /s revealed values of 40.44+/-21.58/22.89+/-16.64Nm and 53.55+/-24.26/34.05+/-17.37Nm (P< 0.01) respectively. The evaluation of the total work of the knee flexors and extensors revealed a significant difference (P< 0.01) between the treatment and control group. The Lequesne score was reduced from 13.57+/-1.88 prior to the injections to 7.94+/-2.53 after the treatment (P< 0.01). The pain score was documented with the help of a visual analog scale. The VAS values were reduced at rest from 3.83+/-1.72cm to 1.36+/-1.42cm and during weight bearing from 7.57+/-1.34cm to 3.75+/-1.32cm in the treatment group (P< 0.01).\n This controlled prospective clinical trial confirmed that 5 weekly intraarticular injections of HA (Hyalart) in patients with OA of the knee provide pain relief and functional improvements.\n Copyright 2002 OsteoArthritis Research Society International. Published by Elsevier Science Ltd. All rights reserved.", "The goal of this study was to determine whether hyaluronic acid (HA) or progressive knee exercises (PE) can improve functional parameters in patients with osteoarthritis (OA) of the knee. In a prospective clinical trial 200 knees (105 patients) with radiographic Kellgren Lawrence grade III OA were randomized and received either three intra-articular injections of hyaluronic acid (Hylan G-F 20) at one-week intervals or PE for 6 weeks. Patients were evaluated by use of the Hospital for Special Surgery (HSS) Knee Score and followed-up for 18 months. Total HSS score for HA and PE patients improved from 62.6 +/- 13.8 to 88.8 +/- 11.1 and from 65.4 +/- 12.3 to 88.3 +/- 9.1, respectively, at the end of the trial (P < 0.01). There were no statistically significant differences between the groups. Twenty-one patients of the HA group were excluded from the study because they had received another form of therapy. All patients in the PE group completed the trial. The patients who dropped out had also significant improvement from 57.0 +/- 12.9 to 76.7 +/- 11.9 (P < 0.01). This prospective randomized trial confirmed that both HA injections and PE result in functional improvement. HA injections also increase the levels of satisfaction of the OA patients." ]	Based on the aforementioned analyses, viscosupplementation is an effective treatment for OA of the knee with beneficial effects: on pain, function and patient global assessment; and at different post injection periods but especially at the 5 to 13 week post injection period. It is of note that the magnitude of the clinical effect, as expressed by the WMD and standardised mean difference (SMD) from the RevMan 4.2 output, is different for different products, comparisons, timepoints, variables and trial designs. However, there are few randomised head-to-head comparisons of different viscosupplements and readers should be cautious, therefore, in drawing conclusions regarding the relative value of different products. The clinical effect for some products, against placebo, on some variables at some timepoints is in the moderate to large effect-size range. Readers should refer to relevant tables to review specific detail given the heterogeneity in effects across the product class and some discrepancies observed between the RevMan 4.2 analyses and the original publications. Overall, the analyses performed are positive for the HA class and particularly positive for some products with respect to certain variables and timepoints, such as pain on weight bearing at 5 to 13 weeks postinjection. In general, sample-size restrictions preclude any definitive comment on the safety of the HA class of products; however, within the constraints of the trial designs employed no major safety issues were detected. In some analyses viscosupplements were comparable in efficacy to systemic forms of active intervention, with more local reactions but fewer systemic adverse events. In other analyses HA products had more prolonged effects than IA corticosteroids. Overall, the aforementioned analyses support the use of the HA class of products in the treatment of knee OA.
CD007275	[ "18420756", "17539899", "18261131", "15216550", "17100502", "9426791", "14551306", "15203777", "21667366" ]	[ "Psychological and behavioural impact of genetic testing smokers for lung cancer risk: a phase II exploratory trial.", "Genetic testing for heart disease susceptibility: potential impact on motivation to quit smoking.", "The impact of genetic testing for Crohn's disease, risk magnitude and graphical format on motivation to stop smoking: an experimental analogue study.", "Psychological impact of genetic testing for familial hypercholesterolemia within a previously aware population: a randomized controlled trial.", "Can genetic risk information enhance motivation for smoking cessation? An analogue study.", "Genetic susceptibility testing in smoking-cessation treatment: one-year outcomes of a randomized trial.", "Long-term psychological impact of carrying a BRCA1/2 mutation and prophylactic surgery: a 5-year follow-up study.", "Obtaining DNA from a geographically dispersed cohort of current and former smokers: use of mail-based mouthwash collection and monetary incentives.", "A novel recruitment message to increase enrollment into a smoking cessation treatment program: preliminary results from a randomized trial." ]	[ "The behavioural and psychological impact of genetic testing for lung cancer susceptibility was examined among smokers (N = 61) who were randomly allocated to a GSTM1 genetic testing group (with GSTM1-missing or GSTM1-present result) or no-test control group. The GSTM1-missing (higher risk) group reported greater motivation to quit smoking, and both genetic testing groups reported lower depression than the control group at one-week follow-up (p < .05 for all). Differences were not significant at two months follow-up. This study indicates the feasibility of much-needed research into the risks and benefits for individuals of emerging lifestyle-related genetic susceptibility tests.", "As genetic tests for common gene variants and multifactorial, lifestyle-related conditions become available, it will be increasingly important to determine the psychological and behavioral impact of this emerging class of genetic tests. Our aim was to examine the potential impact of genetic testing for heart disease susceptibility on psychological predictors of smoking cessation. Two hundred and sixty-one smokers were asked to imagine that they had undergone a test for heart disease risk. They were randomly assigned to a genetic test scenario (low- or high-risk result) or an oxidative test scenario (high-risk result). Smokers in the genetic test-high risk group reported greater intention to quit smoking than smokers in the oxidative test-high risk group (p = 0.009); 30% of this was mediated by their holding stronger beliefs that quitting would reduce their heart disease risk (outcome expectations) (p = 0.011). The effect of genetic test-high risk feedback on outcome expectations was greatest amongst smokers with no heart disease family history (p = 0.038). The results suggest that genetic testing for heart disease risk may enhance interventions designed to improve health via increasing smoking cessation rates. Whether the findings hold true in studies that use real rather than hypothetical genetic tests remains to be seen.", "Genetic tests may motivate risk-reducing behaviour more than other types of tests because they generate higher risk magnitudes and because their results have high personal relevance. To date, trial designs have not allowed the disentangling of the effects of these two factors. This analogue study examines the independent impacts of risk magnitude and provenance, and of risk display type, on motivation to quit smoking. A total of 180 smokers were randomly allocated to one of the 18 Crohn's disease risk vignettes in a 3 (risk provenance: family history. genetic test mutation positive. genetic test mutation negative) x 3 (risk magnitude: 3%, 6%, 50%) x 2 (display: grouped or dispersed icons) design. The 50% group had significantly higher intentions to quit than the 3% group. A significant risk provenance x magnitude interaction showed that participants in 50% or 6% groups were equally motivated, regardless of risk provenance, while participants in the 3% group had higher intentions associated with a mutation negative result than with a result based on family history alone. Grouped icon displays were more motivating than the dispersed icons. Using genetic tests to estimate risks of common complex conditions may not motivate behaviour change beyond the impact of the numerical risk estimates derived from such tests.", "This trial tests the hypothesis that confirming a clinical diagnosis of familial hypercholesterolemia (FH) by finding a genetic mutation reduces patients' perceptions of control over the disease and adherence to risk-reducing behaviors. Three hundred forty-one families, comprising 341 hypercholesterolemia probands and 128 adult relatives, were randomized to one of two groups: (a) routine clinical diagnosis; (b) routine clinical diagnosis plus genetic testing (mutation searching in probands and direct gene testing in relatives). The main outcome measures were perceptions of control over hypercholesterolemia, adherence to cholesterol-lowering medication, diet, physical activity, and smoking. There was no support for the main hypothesis: finding a mutation had no impact on perceived control or adherence to risk-reducing behavior (all P-values > 0.10). While all groups believed that lowering cholesterol was an effective way of reducing the risk of a heart attack, participants in whom a mutation was found believed less strongly in the efficacy of diet in reducing their cholesterol level (P = 0.02 at 6 months) and showed a trend in believing more strongly in the efficacy of cholesterol-lowering medication (P = 0.06 at 6 months). In conclusion, finding a mutation to confirm a clinical diagnosis of FH in a previously aware population does not reduce perceptions of control or adherence to risk-reducing behaviors. The pattern of findings leads to the new hypothesis that genetic testing does not affect the extent to which people feel they have control over a condition, but does affect their perceptions of how control is most effectively achieved. Further work is needed to determine whether similar results will be obtained in populations with little previous awareness of their risks.\n Copyright 2004 Wiley-Liss, Inc.", "Protection motivation theory and the extended parallel processing model are used to predict the motivational impact of information regarding a genetic susceptibility to heart disease. One hundred ninety-eight smokers read 1 of 3 vignettes: gene positive, gene negative, or standard smoking risk information. Analyses examined whether the impact of type of risk information was moderated by smokers' self-efficacy (SE) levels. Key outcomes were intention to quit and intention to attend an information session about quitting. There were significant main effects of SE and of receiving gene-positive risk information on intentions to quit. There was a significant Risk x SE interaction on intentions to attend an information session. SE was not associated with intentions to attend the information session for smokers in the gene-positive group. Intentions to attend the session were negatively associated with SE for smokers in the lower risk groups. Implications for using genetic risk information to motivate smoking cessation are discussed.\n Copyright 2006 APA, all rights reserved.", "This study evaluated the long-term impact of genetic susceptibility biomarker feedback on smoking behavior change and symptoms of depression in 426 male and female smokers. Smokers were randomized to one of three smoking-cessation interventions: minimal contact quit-smoking counseling (QSC), QSC + exposure biomarker feedback (EBF), and QSC + EBF + biomarker feedback about genetic susceptibility to lung cancer (SBF). The logistic regression model for quit attempt revealed a significant main effect for treatment such that participants in the SBF group were more than two times more likely to make a quit attempt than participants in the QSC group. There was not a significant difference between EBF and QSC participants. The results also revealed a significant effect for baseline stage of change. Those smokers in the preparation stage at baseline were more than three times more likely to make a quit attempt over the 12 months following treatment. The models for 30-day cessation and follow-up smoking rate revealed no significant main or interacting effects for treatment. A repeated measures analysis of variance revealed a significant main effect for time, indicating that an initial increase in depression in the genetic susceptibility group was not maintained over time. Genetic susceptibility feedback has the intended effects on motivation to quit, but it may need to be delivered within a more intensive smoking-cessation treatment for the heightened motivation to translate into smoking cessation.", "To explore long-term psychosocial consequences of carrying a BRCA1/2 mutation and to identify possible risk factors for long-term psychological distress.\n Five years after genetic test disclosure, 65 female participants (23 carriers, 42 noncarriers) of our psychological follow-up study completed a questionnaire and 51 participants were interviewed. We assessed general and hereditary cancer-related distress, risk perception, openness to discuss the test result with relatives, body image and sexual functioning.\n Carriers did not differ from noncarriers on several distress measures and both groups showed a significant increase in anxiety and depression from 1 to 5 years follow-up. Carriers having undergone prophylactic surgery (21 of 23 carriers) had a less favorable body image than noncarriers and 70% reported changes in the sexual relationship. A major psychological benefit of prophylactic surgery was a reduction in the fear of developing cancer. Predictors of long-term distress were hereditary cancer-related distress at blood sampling, having young children, and having lost a relative to breast/ovarian cancer. Long-term distress was also associated with less open communication about the test result within the family, changes in relationships with relatives, doubting about the validity of the test result, and higher risk perception.\n Our findings support the emerging consensus that genetic predisposition testing for BRCA1/2 does not pose major mental health risks, but our findings also show that the impact of prophylactic surgery on aspects such as body image and sexuality should not be underestimated, and that some women are at risk for high distress, and as a result, need more attentive care.", "The feasibility of collecting DNA through the mail from a cohort of current and former smokers was assessed. Also examined was whether monetary incentives would increase response rates. A random sample of 300 subjects, stratified by 20 U.S. communities, was selected to participate. The sampling frame included the 6,726 people who were in both the Community Intervention Trial for Smoking Cessation (COMMIT) between 1988 and 1993 and the follow-up study in 2001, and who consented to being contacted again. Subjects were further randomized within communities to incentive arms of 10 US dollars, 2 US dollars, or 0 US dollars. A total of 110 usable samples were returned (37%), and the 10 US dollars incentive arm had the highest response (43%). Logistic regression revealed no significant predictors of sending a DNA sample, although in a larger study, similar-sized odds ratios would be statistically significant for subjects who received the 10 US dollars incentive and for those who were White, female, or college graduates or whose household incomes were more than 60,000 US dollars per year. The spectrophotometer-determined median DNA yield was 44.93 microg (range=4.00-425.86 microg). Assuming that 50 ng of DNA would be needed for polymerase chain reaction amplification to determine any given genotype, 80-8,517 runs would be attainable. Qualitative findings suggest several methodological improvements to boost response rates. Institutional review board requirements, which are standardized on the inpatient, clinical protocol model, stipulated that noninstitutionally based subjects needed a witness to initial and date every page as well as sign the consent form. This pilot study showed that this requirement could pose some challenges in population-based research.", "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." ]	Mindful of the weak evidence based on a small number of studies of limited quality, the results of this review suggest that communicating DNA-based disease risk estimates has little or no effect on smoking and physical activity. It may have a small effect on self-reported diet and on intentions to change behaviour. Claims that receiving DNA-based test results motivates people to change their behaviour are not supported by evidence. Larger and better-quality RCTs are needed.
CD005342	[ "20619634", "16983741" ]	[ "Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer--results from two randomised studies.", "Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer." ]	[ "Endometrial cancer patients with high grade tumours, deep myometrial invasion or advanced stage disease have a poor prognosis. Randomised studies have demonstrated the prevention of loco-regional relapses with radiotherapy (RT) with no effect on overall survival (OS). The possible additive effect of chemotherapy (CT) remains unclear. Two randomised clinical trials (NSGO-EC-9501/EORTC-55991 and MaNGO ILIADE-III) were undertaken to clarify if sequential combination of chemotherapy and radiotherapy improves progression-free survival (PFS) in high-risk endometrial cancer. The two studies were pooled.\n Patients (n=540; 534 evaluable) with operated endometrial cancer International Federation of Obstetrics and Gynaecology (FIGO) stage I-III with no residual tumour and prognostic factors implying high-risk were randomly allocated to adjuvant radiotherapy with or without sequential chemotherapy.\n In the NSGO/EORTC study, the combined modality treatment was associated with 36% reduction in the risk for relapse or death (hazard ratio (HR) 0.64, 95%confidence interval (CI) 0.41-0.99; P=0.04); two-sided tests were used. The result from the Gynaecologic Oncology group at the Mario Negri Institute (MaNGO)-study pointed in the same direction (HR 0.61), but was not significant. In the combined analysis, the estimate of risk for relapse or death was similar but with narrower confidence limits (HR 0.63, CI 0.44-0.89; P=0.009). Neither study showed significant differences in the overall survival. In the combined analysis, overall survival approached statistical significance (HR 0.69, CI 0.46-1.03; P=0.07) and cancer-specific survival (CSS) was significant (HR 0.55, CI 0.35-0.88; P=0.01).\n Addition of adjuvant chemotherapy to radiation improves progression-free survival in operated endometrial cancer patients with no residual tumour and a high-risk profile. A remaining question for future studies is if addition of radiotherapy to chemotherapy improves the results.\n Copyright 2010 Elsevier Ltd. All rights reserved.", "Neoadjuvant chemoradiotherapy does not alter anal sphincter preservation or postoperative complications compared with short-course radiotherapy alone in patients with clinical stage T3 or T4 resectable rectal cancer. The aim of this study was to compare survival, local control and late toxicity in the two treatment groups.\n The study randomized 312 patients to receive either preoperative irradiation (25 Gy in five fractions of 5 Gy) and surgery within 7 days or chemoradiation (50.4 Gy in 28 fractions of 1.8 Gy, bolus 5-fluorouracil and leucovorin) and surgery 4-6 weeks later. The median follow-up of living patients was 48 (range 31-69) months.\n Early radiation toxicity was higher in the chemoradiation group (18.2 versus 3.2 per cent; P < 0.001). The actuarial 4-year overall survival was 67.2 per cent in the short-course group and 66.2 per cent in the chemoradiation group (P = 0.960). Disease-free survival was 58.4 versus 55.6 per cent (P = 0.820), crude incidence of local recurrence was 9.0 versus 14.2 per cent (P = 0.170) and severe late toxicity was 10.1 versus 7.1 per cent (P = 0.360) respectively.\n Neoadjuvant chemoradiation did not increase survival, local control or late toxicity compared with short-course radiotherapy alone." ]	The addition of platinum-based chemotherapy to adjuvant radiotherapy (chemoradiation) may improve survival in women with early stage cervical cancer (IA2-IIA) and risk factors for recurrence. Adjuvant chemoradiation is associated with an increased risk of severe acute toxicity, although it is not clear whether this toxicity is significant in the long-term due to a lack of long-term data. This evidence is limited by the small numbers and poor methodological quality of included studies. We await the results of three ongoing trials, that are likely to have an important impact on our confidence in this evidence.
CD007372	[ "12548322" ]	[ "A randomized controlled trial of outpatient versus inpatient labour induction with vaginal controlled-release prostaglandin-E2: effectiveness and satisfaction." ]	[ "Outpatient management in obstetrics is expanding, but evidence to support outpatient labour induction is needed.\n To compare the effectiveness, acceptability, duration of hospitalization, and safety of outpatient and inpatient induction of labour with intravaginal controlled-release prosta-glandin-E2 (CR-PGE2).\n A prospective, randomized, controlled trial enrolled 300 women at term with parity < or = 5 and singleton pregnancies in cephalic presentation. Each had an unscarred uterus, a normal non-stress test (NST), and a Bishop score of < or = 6. After insertion of the CR-PGE2, and 1 hour of monitoring, those in the outpatient group were discharged home, to return with onset of labour or 12 hours later for an NST. If not already in labour 24 hours later, the women returned for inpatient induction. Vaginal examination was not repeated before 24 hours unless the patient was contracting and required analgesia. Inpatients remained on the antepartum ward but were otherwise treated similarly. The women in both groups reported ratings of satisfaction, pain, and anxiety over the telephone until they were in labour.\n There were 150 women randomized to outpatient and 150 women to inpatient induction of labour. The number of women who were in labour or who delivered by 24 hours in the outpatient group was 115 (0.77, 95% confidence interval [CI] 0.70-0.84) and in the inpatient group was 107 (0.72, 95% CI 0.64-0.79). The median times to labour were 9.8 hours (95% CI, 8.1-11.4) and 11.4 hours (95% CI, 10.1-12.7), and to delivery were 21.4 hours (95% CI, 19.2-23.5) and 20.7 hours (95% CI, 18.4-23.0), for the outpatient and inpatient groups, respectively. In the outpatient group, 56% of women reported high satisfaction during the initial 12 hours of induction compared to 39% in the inpatient group (p < 0.008). Ratings of pain and anxiety during the first 12 hours of induction were similar. In the outpatient group, women were at home for a median of 8 hours (95% CI, 6.7-9.4) before labour and delivery. There were no significant differences in adverse outcomes.\n This study suggests that outpatient induction of labour with intravaginal CR-PGE2 may be a reasonable option for selected low-risk women; however, further study is needed to confirm the safety of this approach." ]	The data available to evaluate the efficacy or potential hazards of outpatient induction are limited. It is, therefore, not yet possible to determine whether induction of labour is effective and safe in outpatient settings. [Note: The four citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]
CD007062	[ "8245589", "14526317", "18472878", "2206065", "8885732", "9307346" ]	[ "[The efficacy of prophylactic antibiotic and tocolytic therapy for premature rupture of the membranes--a prospective randomized study].", "Duration of antibiotic therapy after preterm premature rupture of fetal membranes.", "Randomized trial of antibiotics in addition to tocolytic therapy to treat preterm labor.", "Antibiotic therapy in preterm premature rupture of membranes: a randomized, prospective, double-blind trial.", "The clinical efficacy of oral tocolytic therapy.", "Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes. A randomized controlled trial. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network." ]	[ "A comparative study in patients with premature rupture of the membranes (PROM) from 25 to 34 weeks of gestation was carried out, prospectively. Group 1 (34 patients) was given aggressively intrauterine therapy including the administration of tocolytic agents (ritodrine and/or magnesium sulfate) and prophylactic antibiotics (AB-PC 2g/day). Group 2 (41 patients) was managed conservatively with bed rest only. At the time of admission to the study, there were no clinical signs of infection, fetal distress, or active labor in either group. All patients were delivered if the pregnancy had reached 35 weeks of gestation or later, had established labor, or developed evidence of chorioamnionitis or fetal distress. Prolongation for more than 72 hours was greater in group 1 than in group 2. There was no difference in the incidence of chorioamnionitis, postpartum endometritis, or placental infection in the groups. However, the incidence of a low Apgar score (7 < at 5 min), requiring artificial ventilation, and infection was more common in group 1. It is concluded that the use of antibiotics and tocolytics might make the management of PROM more complicated.", "This study was undertaken to compare the efficacy of 3 days versus 7 days of ampicillin in prolonging gestation for at least 7 days in women with preterm premature rupture of membranes (PPROM).\n We performed a randomized clinical trial comparing 3 days of ampicillin with 7 days ampicillin in patients with PPROM. Our primary outcome was the prolongation of pregnancy for at least 7 days. Secondary outcomes included rates of chorioamnionitis, postpartum endometritis, and neonatal morbidity and mortality.\n Forty-eight patients were randomly selected. There was no statistically significant difference in the ability to achieve a 7-day latency (relative risk 0.83, 95% CI 0.51-1.38). In addition, there was no statistically significant difference in the rates of chorioamnionitis, endometritis, and our composite neonatal morbidity.\n In patients with PPROM, length of antibiotic therapy does not change the rate of a 7-day latency or affect the rate of chorioamnionitis, postpartum endometritis, or neonatal morbidity.", "The objective of this study was to assess whether antibiotic therapy plus tocolysis given to women in preterm labor would prolong pregnancy compared with tocolysis alone.\n A randomized, double-blind trial of intravenous mezlocillin and oral erythromycin therapy vs. placebo was used in addition to tocolysis among women in preterm labor < or =34 weeks gestation with intact membranes. Amniocentesis was performed, and chorioamnionic membranes were examined histologically and cultured for microorganisms after delivery.\n Clinical characteristics including gestational age at enrollment, frequency of contractions, cervical Bishop's score, and white blood cell count on admission were similar in the 2 groups. Antibiotic therapy was well tolerated. No significant differences in the interval to delivery, birth weight, and neonatal outcomes were observed between the 2 groups. Women in the antibiotic group had a significantly lower incidence of postpartum infections compared with women in the placebo group. Patients with evidence of upper genital tract infection in either group had a significantly shorter interval to delivery, lower gestational age at delivery, lower mean birth weight, and increased neonatal hospitalization time.\n Lack of an antibiotic effect on the gestational age at delivery may be due to the low prevalence of upper genital tract infection among unselected women in preterm labor, to advanced preterm labor unresponsive to antibiotic therapy, or to an inability of antibiotics given alone to inhibit the cytokine response. Further work is needed to identify markers of upper genital tract infection among women in preterm labor and to evaluate other potential therapeutic interventions.", "The use of antibiotics in the management of preterm, premature rupture of membranes remains controversial. By use of a prospective randomized double-blind design we investigated the maternal-fetal benefits associated with antibiotic therapy in 85 women with premature rupture of membranes at 34 weeks' estimated gestational age. In the treatment group 40 patients received intravenous mezlocillin for 48 hours followed by oral ampicillin until delivery. In the control group 45 patients received intravenous and oral placebo. Patients who received antibiotics had chorioamnionitis and endometritis less frequently than the control group (p less than 0.01 and p less than 0.05). Pathologic examination of the placentas showed a lower incidence of chorioamnionitis in the treatment group (p less than 0.05). The period from premature rupture of membranes to delivery (latency) was prolonged with antibiotics (p less than 0.05) and resulted in significant weight gain in the infants in the antibiotic group (p less than 0.0001). These infants also had higher 1- and 5-minute Apgar scores. Clinically suspected sepsis, respiratory distress syndrome, intraventricular hemorrhage, perinatal death rate, and prolonged hospitalization (greater than 30 days) were also increased in the control group.", "Our purpose was to determine whether maintenance oral tocolytic therapy after preterm labor stabilization decreases uterine activity, reduces the rate of recurrent preterm labor and subsequent preterm birth, or improves neonatal outcome.\n Women with documented idiopathic preterm labor stabilized with acute tocolytic therapy were randomized to three groups: placebo, terbutaline 5 mg, or magnesium chloride 128 mg, all given orally every 4 hours. Patients and providers were blinded to group assignment. All subjects were enrolled in a comprehensive system of preterm birth prevention that included preterm labor education, weekly clinic visits, home uterine contraction assessment, daily phone contact, and 24-hour perinatal nurse access.\n Of the 248 patients who were randomized, 39 were delivered before discharge and 4 were lost to follow-up, leaving 205 for final analysis: 68 placebo, 72 terbutaline, and 65 magnesium. The terbutaline group had significantly more side effects than the placebo group did. All groups had otherwise similar perinatal outcomes when confounding variables were controlled for. Overall, the three groups had a preterm birth rate < 37 weeks of 55.6% delivery, < 34 weeks of 15.6%, a 20.4% rate of newborn intensive care unit admission, and a mean neonatal length of stay of 6.3 days.\n Maintenance oral tocolytic therapy did not decrease uterine activity, reduce the rate of recurrent preterm labor or preterm birth, or improve perinatal outcome. Overall improvement in perinatal outcome may be achieved with a comprehensive program of preterm birth prevention without the use of maintenance oral tocolytic therapy.", "Intrauterine infection is thought to be one cause of preterm premature rupture of the membranes (PPROM). Antibiotic therapy has been shown to prolong pregnancy, but the effect on infant morbidity has been inconsistent.\n To determine if antibiotic treatment during expectant management of PPROM will reduce infant morbidity.\n Randomized, double-blind, placebo-controlled trial.\n University hospitals of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.\n A total of 614 of 804 eligible gravidas with PPROM between 24 weeks' and 0 days' and 32 weeks' and 0 days' gestation who were considered candidates for pregnancy prolongation and had not received corticosteroids for fetal maturation or antibiotic treatment within 1 week of randomization.\n Intravenous ampicillin (2-g dose every 6 hours) and erythromycin (250-mg dose every 6 hours) for 48 hours followed by oral amoxicillin (250-mg dose every 8 hours) and erythromycin base (333-mg dose every 8 hours) for 5 days vs a matching placebo regimen. Group B streptococcus (GBS) carriers were identified and treated. Tocolysis and corticosteroids were prohibited after randomization.\n The composite primary outcome included pregnancies complicated by at least one of the following: fetal or infant death, respiratory distress, severe intraventricular hemorrhage, stage 2 or 3 necrotizing enterocolitis, or sepsis within 72 hours of birth. These perinatal morbidities were also evaluated individually and pregnancy prolongation was assessed.\n In the total study population, the primary outcome (44.1 % vs 52.9%; P=.04), respiratory distress (40.5% vs 48.7%; P=.04), and necrotizing enterocolitis (2.3% vs 5.8%; P=.03) were less frequent with antibiotics. In the GBS-negative cohort, the antibiotic group had less frequent primary outcome (44.5% vs 54.5%; P=.03), respiratory distress (40.8% vs 50.6%; P=.03), overall sepsis (8.4% vs 15.6%; P=.01), pneumonia (2.9% vs 7.0%; P=.04), and other morbidities. Among GBS-negative women, significant pregnancy prolongation was seen with antibiotics (P<.001).\n We recommend that women with expectantly managed PPROM remote from term receive antibiotics to reduce infant morbidity." ]	Our review suggests there is insufficient evidence to support tocolytic therapy for women with PPROM, as there was an increase in maternal chorioamnionitis without significant benefits to the infant. However, studies did not consistently administer latency antibiotics and corticosteroids, both of which are now considered standard of care.
CD001255	[ "15374046", "12697798", "12521969", "12810740", "12851191", "17652295", "19137351", "11605747", "15381506", "11315240", "11087879", "14997286", "8093267", "16238765" ]	[ "Effectiveness and acceptability of a newly designed hip protector: a pilot study.", "Prevention of hip fractures by external hip protectors: a randomized controlled trial.", "Effect on hip fractures of increased use of hip protectors in nursing homes: cluster randomised controlled trial.", "A randomised trial of hip protector use by frail older women living in their own homes.", "Randomised controlled trial of hip protectors for the prevention of second hip fractures.", "Efficacy of a hip protector to prevent hip fracture in nursing home residents: the HIP PRO randomized controlled trial.", "External hip protectors are effective for the elderly with higher-than-average risk factors for hip fractures.", "Acceptance of hip protectors for hip fracture prevention in nursing homes.", "A cluster randomised controlled trial to evaluate a policy of making hip protectors available to residents of nursing homes.", "Hip fracture prevention trial using hip protectors in Japanese nursing homes.", "Prevention of hip fracture in elderly people with use of a hip protector.", "Randomized controlled trial of hip protectors among women living in the community.", "Effect of external hip protectors on hip fractures.", "A randomized clinical trial of the effectiveness of a discharge planning intervention in hospitalized elders with hip fracture due to falling." ]	[ "Hip fracture has a significant economic and personal cost, involving hospital admission and functional impairment for elderly people. To assess the benefit of using a newly designed hip protector (new material and new design) to prevent fracture in a realistic setting, a randomised intervention-control design was used to trial the effectiveness of pads worn by high falls risk residents (n=71) in nursing home for 9 months. 40 residents were in the intervention group and 31 were in the control group. A profile of falls, including time of day, and orientation was obtained to demonstrate the potential effectiveness of the protectors for injury prevention. Acceptance of the hip protector was also surveyed amongst nursing home staff and residents. One hundred and one falls and six fractures occurred in the control group. In contrast, one hundred and ninety one falls and three fractures occurred in the hip protector (pads) group. The three fractures in the protector wearing group occurred when pads were not in place. This was extrapolated as 1 in every 16.8 falls and 1 in every 63.7 falls resulting in fracture in the two groups, respectively. The relative risk of fracture was 0.264 (95% CI=0.073-0.959) when the fracture incidence rate in the intervention group (three fractures per 191 falls) was compared to the control group (six fractures per 101 falls). This is a statistically significant result and implies that this newly designed hip protector is effective in preventing hip fracture. The majority of falls occurred during the day, which was when protectors were worn in this study, but the data on orientation was incomplete, with direction unknown in 74% of falls. Compliance was an issue, which was interpreted as only 50.3% of falls recorded with protectors in place. Dementia was identified as the explanation for this as the pads were often removed by these residents who comprised the majority of participants. Perception of low risk was the primary barrier to residents accepting the intervention. Comfort of protectors was not a significant concern for staff or residents, and only staff described appearance as an issue. In conclusion, the newly designed hip protector is protective against fractures in a realistic setting. Compliance and acceptance of the protectors will ultimately determine the viability of this prophylaxis.", "Several randomized controlled trials have been performed to examine the effectiveness of external hip protectors in reducing the incidence of hip fractures, but the results are controversial.\n To examine the effectiveness of hip protectors in reducing the incidence of hip fractures in an elderly high-risk population.\n Randomized controlled trial of elderly persons aged 70 years or older, who have low bone density, and are at high risk for falls. Participants lived in apartment houses for the elderly, homes for the elderly, and nursing homes in Amsterdam and surrounding areas in the Netherlands. They were enrolled in the study between March 1999 and March 2001; the mean follow-up was 69.6 weeks. Of the 830 persons who were screened, 561 persons were enrolled.\n External hip protector. Both groups received written information on bone health and risk factors for falls.\n Time to first hip fracture. Survival analysis was used to include all participants for the time they participated.\n In the intervention group, 18 hip fractures occurred vs 20 in the control group. Four hip fractures in the intervention group occurred while an individual was wearing a hip protector. At least 4 hip fractures in the intervention group occurred late at night or early in the morning. Both in univariate analysis (log-rank P =.86) and in multivariate analysis (hazard ratio [HR], 1.05; 95% confidence interval [CI], 0.55-2.03), no statistically significant difference between the intervention group and control group was found with regard to time to first hip fracture. In addition, the per protocol analysis in compliant participants did not show a statistically significant difference between the groups (HR, 0.77; 95% CI, 0.25-2.38).\n The hip protector studied was not effective in preventing hip fractures.", "To assess the effects of an intervention programme designed to increase use of hip protectors in elderly people in nursing homes.\n Cluster randomised controlled trial with 18 months of follow up.\n Nursing homes in Hamburg (25 clusters in intervention group; 24 in control group). Participants: Residents with a high risk of falling (459 in intervention group; 483 in control group). Intervention: Single education session for nursing staff, who then educated residents; provision of three hip protectors per resident in intervention group. Usual care optimised by brief information to nursing staff about hip protectors and provision of two hip protectors per cluster for demonstration purposes.\n Incidence of hip fractures.\n Mean follow up was 15 months for the intervention group and 14 months for the control group. In total 167 residents in the intervention group and 207 in the control group died or moved away. There were 21 hip fractures in 21 (4.6%) residents in the intervention group and 42 hip fractures in 39 (8.1%) residents in the control group (relative risk 0.57, absolute risk difference -3.5%, 95% confidence interval -7.3% to 0.3%, P=0.072). After adjustment for the cluster randomisation the proportions of fallers who used a hip protector were 68% and 15% respectively (mean difference 53%, 38% to 67%, P=0.0001). There were 39 other fractures in the intervention group and 38 in the control group.\n The introduction of a structured education programme and the provision of free hip protectors in nursing homes increases the use of protectors and may reduce the number of hip fractures.", "To investigate the efficacy and effectiveness of hip protectors in frail community living older women.\n Randomised controlled trial.\n Aged care health services in New South Wales, Australia.\n 600 women 74 years of age or more (mean age 83 years), who had two or more falls or one fall requiring hospital admission in the previous year, and who lived in their own homes.\n Use of hip protectors.\n Adherence with use of hip protectors, falls, incidence of hip fracture, and adverse effects of use of hip protectors.\n Adherence was approximately 53% over the duration of the study and hip protectors were worn at the time of 51% of falls in the intervention group. The risk of hip fracture when falling while wearing hip protectors, compared with a fall with no hip protectors in place, was significantly reduced (relative risk (RR) 0.23, 95% confidence interval (CI) 0.08 to 0.67). On an intention to treat analysis, 21 and 22 hip fractures occurred in the intervention and control groups respectively (adjusted RR 0.92, 95% CI 0.51 to 1.68). Three users of hip protectors sustained a hip fracture while wearing properly applied protectors, while 16 hip protector users (5%) developed minor local complications.\n Hip protectors prevent hip fractures in community dwelling older women if worn at the time of a fall. The overall effectiveness of hip protectors was not established in this study, because of incomplete adherence with use of the protectors, and limited statistical power.", "to assess whether the use of Safehip hip protectors would prevent second hip fractures among men and women living in the community.\n pragmatic randomised controlled trial.\n people living in the community.\n men and women aged 70 years and over who had sustained one hip fracture and who were living in the community.\n 366 men and women who were either living outside residential care or were about to be discharged back home were randomised to receive three pairs of hip protectors or to act as controls. Approximately 34% of participants allocated to receive hip protectors wore them every day. After a median follow up of 14 months 8 participants had a second hip fracture with 6 in the intervention and 2 in the control group (Odds Ratio for second hip fracture=3.10, 95% confidence interval 0.62-15.58). Hip protectors had no effect on risk of other fractures or on falls.\n this trial does not suggest a benefit of the studied hip protector among people living outside residential accommodation.", "Past studies of the efficacy of hip protectors to prevent hip fracture in nursing home residents have had conflicting results, possibly due to potential biases from clustered randomization designs and modest adherence to intervention.\n To determine whether an energy-absorbing and energy-dispersing hip protector would reduce the risk of hip fracture when worn by nursing home residents.\n Multicenter, randomized controlled clinical trial in which 37 nursing homes were randomly assigned to having residents wear a 1-sided hip protector on the left or right hip. Participants were 1042 nursing home residents (mean [SD] aged 85 [7] years; 79% women) who consented and adhered to the hip protector use during a 2-week run-in period and were enrolled. Participating facilities were in greater Boston, Massachusetts, St Louis, Missouri, and Baltimore, Maryland from October 2002 to October 2004. Mean duration of participation for nursing home residents was 7.8 months. None were withdrawn because of adverse effects.\n Undergarments with a 1-sided hip protector made of a 0.32-cm outer layer of polyethylene (2.7 kg/m3) backed by a hard high-density polyethylene shield (0.95 cm) that was backed by 0.9 kg/m3 of 1.27-kg ethylene vinyl acetate foam. Each facility was visited 3 times per week to assess adherence and provide staff support.\n Adjudicated hip fracture occurrences on padded vs unpadded hips.\n After a 20-month follow-up (676 person-years of observation), the study was terminated due to a lack of efficacy. The incidence rate of hip fracture on protected vs unprotected hips did not differ (3.1%; 95% confidence interval [CI], 1.8%-4.4% vs 2.5%; 95% CI, 1.3%-3.7%; P = .70). For the 334 nursing home residents with greater than 80% adherence to hip protector use, the incidence rate of hip fracture on protected vs unprotected hips did not differ (5.3%; 95% CI, 2.6%-8.8% vs 3.5%; 95% CI, 1.3%-5.7%; P = .42). Overall adherence was 73.8%.\n In this clinical trial of an energy-absorbing/shunting hip protector conducted in US nursing homes, we were unable to detect a protective effect on the risk of hip fracture, despite good adherence to protocol. These results add to the increasing body of evidence that hip protectors, as currently designed, are not effective for preventing hip fracture among nursing home residents.\n clinicaltrials.gov Identifier: NCT00058864.", "In our cluster randomised controlled trial for efficacy of hip protector with 672 ambulatory elderly women, a hip protector was more effective for prevention of hip fractures in residents with fall history (n = 202; hazard ratio (HR), 0.375; 95%CI, 0.14-0.98; p = 0.05) and body-mass index (BMI) < or = 19.0 (n = 206; HR, 0.37; 95%CI, 0.14-0.95; p = 0.04) by a Cox proportional hazards regression model.\n Hip fractures result from both osteoporosis and falling. A potentially cost-effective method of preventing hip fractures involves the use of hip protectors but recent studies have revealed the uncertain effectiveness of hip protectors even in institutional settings.\n This study was a cluster randomised controlled trial with nursing homes. We randomly assigned 76 homes with 672 ambulatory but frail elderly women. Several risk factors were assessed at baseline and incorporated into a Cox proportional hazards regression model. UMIN Clinical Trials Registry number is UMIN000000467. Research period was between January 2004 and March 2006.\n In the intervention group, 19 hip fractures occurred (54.0/1,000 person-years), whereas 39 hip fractures occurred in the control group (78.8/1,000 person-years). Hazard ratio of hip fracture in the intervention group was 0.56 (95%CI, 0.31-1.03; p = 0.06) after adjusting for risk factors. In subgroup analysis, hip protectors were more effective for prevention of hip fractures in residents with fall history (n = 202; HR, 0.375; 95%CI, 0.14-0.98; p = 0.05) and BMI < or = 19.0 (n = 206; HR, 0.37; 95%CI, 0.14-0.95; p = 0.04). Overall compliance with use of hip protectors was 79.7%.\n Risk of hip fracture can be reduced by hip protectors among elderly women with fall history and low BMI.", "In order to prevent hip fractures 548 fall-prone senior citizens living in 20 nursing homes participated in a randomized controlled trial of hip protectors. One hundred and sixty-four were randomly selected into the control group and 384 into the intervention group. Of the patients in the intervention group 138 (35.9%) wore the protector throughout the whole 10 months of the study's duration, 124 (32.3%) quit wearing the protectors after an initial wearing period and 122 (31.8%) refused to wear them at all. The regular wearers had the protector on during an average of roughly 12 hours a day, so they were protected for 50% of their exposure time (including at night). Fifty-nine percent of the drop-outs stopped wearing the protectors in the first two study months, mostly for non-medical reasons. Calculation by a forecasting model showed that those senior citizens who were initially prepared to wear the protector tended to be those who were physically restricted.", "to evaluate the effectiveness of a policy of making hip protectors available to residents of nursing homes.\n a cluster randomised controlled trial of the policy in nursing and residential homes, with the home as the unit of randomisation.\n 127 nursing and residential homes in the greater Belfast area of Northern Ireland.\n 40 homes in the intervention group (representing 1,366 occupied beds) and 87 homes in the control group (representing 2,751 occupied beds).\n a policy of making hip protectors available free of charge to residents of nursing homes and supporting the implementation process by employing a nurse facilitator to encourage staff in the homes to promote their use, over a 72-week period.\n the rate of hip fractures in intervention and control homes, and the level of adherence to use of hip protectors.\n there were 85 hip fractures in the intervention homes and 163 in the control homes. The mean fracture rate per 100 residents was 6.22 in the intervention homes and 5.92 in the control homes, giving an adjusted rate ratio for the intervention group compared to the control group of 1.05 (95% CI 0.77, 1.43, P = 0.76). Initial acceptance of the hip protectors was 37.2% (508/1,366) with adherence falling to 19.9% (272/1,366) at 72 weeks.\n making hip protectors available to residents of nursing and residential homes did not reduce the rate of hip fracture. This research does not support the introduction of a policy of providing hip protectors to residents of nursing homes.", "A method to protect the hips during falls could effectively reduce the incidence of hip fractures. We report the results of the first hip protector trial in Japan, performed between July 1996, and September 1999. One hundred and sixty-four elderly female residents of nursing homes, with Activities of Daily Living above the wheelchair level, agreed to participate in this study. Among them, 88 were randomly selected to wear a hip protector and 76 controls did not. All falls and resulting injuries were recorded daily. In anthropometric measurements and ultrasonic bone evaluation, no significant differences were found between the two groups, except in height. During an average of 377 days, the wearers and the non-wearers fell a total of 131 and 90 times, respectively. Among the wearers, there were two non-hip fractures and one hip fracture, so the annual hip fracture rate was calculated at 1.2%, against 8 hip fractures among the non-wearers, or 9.7% per year. The hip fracture rate was significantly lower among the wearers than non-wearers, while the annual number of falls per subject and the distribution of fallers remained the same. According to Cox's proportional hazard regression analysis, the effect of the hip protector on hip fracture prevention was independent of anthropometric data, ultrasonic bone assessment values or number of falls. Moreover, even after limiting the subjects to fallers only, the annual hip fracture rate in non-wearers was higher than in wearers (19.8% vs 2.0%) and the annual hip fracture rate per fall in wearers was lower than that in non-wearers (0.8% vs 8.2%). It was thus concluded that the hip protector is a beneficial device for the prevention of hip fractures.", "Hip fractures are common in frail elderly adults worldwide. We investigated the effect of an anatomically designed external hip protector on the risk of these age-related fractures.\n We randomly assigned 1801 ambulatory but frail elderly adults (1409 women and 392 men; mean age, 82 years), in a 1:2 ratio, either to a group that wore a hip protector or to a control group. Fractures of the hip and all other fractures were recorded until the end of the first full month after 62 hip fractures had occurred in the control group. The risk of fracture in the two groups was compared, and in the hip-protector group the risk of fracture was also analyzed according to whether the protector had been in use at the time of a fall.\n During follow-up, 13 subjects in the hip-protector group had a hip fracture, as compared with 67 subjects in the control group. The respective rates of hip fracture were 21.3 and 46.0 per 1000 person-years (relative hazard in the hip-protector group, 0.4; 95 percent confidence interval, 0.2 to 0.8; P=0.008). The risk of pelvic fracture was slightly but not significantly lower in the hip-protector group than in the control group (2 subjects and 12 subjects, respectively, had pelvic fracture) (relative hazard, 0.4; 95 percent confidence interval, 0.1 to 1.8; P > or = 0.05). The risk of other fractures was similar in the two groups. In the hip-protector group, four subjects had a hip fracture (among 1034 falls) while wearing the protector, and nine subjects had a hip fracture (among 370 falls) while not wearing the protector (relative hazard, 0.2; 95 percent confidence interval, 0.05 to 0.5; P=0.002).\n The risk of hip fracture can be reduced in frail elderly adults by the use of an anatomically designed external hip protector.", "To assess whether hip protectors used among women living in the community in the United Kingdom and at high risk of hip fracture, lead to a reduction in hip fracture.\n Pragmatic randomized controlled trial (RCT).\n Primary care with participants being recruited largely from general practitioners' patient lists.\n Women aged 70 years and over with one or more risk factors for hip fracture (i.e., low body weight, current smoker, a prior fracture, family history of hip fracture).\n Three pairs of hip protectors of the \"shell\" type mailed to participants with instructions on how to use them.\n Reduction in hip fractures.\n 1,388 and 2,781 women aged 70 years or over were randomized to be given three pairs of hip protectors or act as controls, respectively. We followed up both groups of women for a minimum of 24 months (maximum 42 months, median 28). Compliance was poor with only 31% of participants reporting that they wore the hip protectors on a daily basis at 12 months. Intention-to-treat analysis showed that there was no statistically significant difference in the unadjusted odds ratios (ORs) of sustaining a hip fracture between the groups (OR = 1.19; 95% confidence interval, 0.80 to 1.78, p = 0.40). Adjustment for important covariates did not materially change these findings (OR = 1.17; 95% CI, 0.78 to 1.75). Comparing the rate of hip fracture between those women who regularly wore the devices and the control group yielded an OR of 1.12 (95% CI, 0.58 to 2.03; p = 0.83).\n This study is the largest RCT of hip protectors to date and provides no evidence of an effect of hip protectors among women living independently and at high risk of fracture.", "Most hip fractures seem to be related to trauma near the hip, so a controlled trial was conducted to investigate the effect of external hip protectors on the prevention of such fractures in residents of a nursing home. 10 of the 28 wards in the nursing home were randomised to receive external hip protectors; thus 167 women and 80 men were given protectors and 277 and 141 men no protectors. A fall register was set up for 2 treatment wards (45 residents) and 2 control wards (76 residents). There were 8 hip and 15 non-hip fractures in the hip-protector group and 31 hip and 27 non-hip fractures in the control group. The relative risk of hip fractures among women and men in the intervention group was 0.44 (95% CI 0.21-0.94). None of the 8 residents in the intervention group who had a hip fracture was wearing the device at the time of the fracture. 154 falls were registered and 20% of these falls produced a direct impact to the hip. In 25 falls direct impact to the hip was sustained at a time when hip protectors were not being worn, and 6 fractures were produced. The study indicates that external hip protectors can prevent hip fractures in nursing-home residents.", "The objective of this study was to examine the effectiveness of a discharge plan in hospitalized elderly patients with hip fracture due to falling.\n Hip fractures are an important cause of morbidity and mortality among older people. Hip fracture patients require ongoing medical and long-term care services. Discharge plan services can play a very important role for these patients, since the services improved their outcome conditions.\n Hip fracture patients aged 65 years and older (n = 126), hospitalized due to falling and discharged from a medical centre in northern Taiwan, were randomly assigned to either a comparison group (the routine care) or experimental group (the discharge planning intervention). The outcomes used to determine the effectiveness of the intervention were: length of hospitalized stay, rate of readmission, repeat falls and survival, and activities of daily living.\n The discharge planning intervention decreased length of stay, rate of readmission and rate of survival and improved activities of daily living for intervention group compared with those of control group. Mean total SF-36 scores of patients in the experimental group were higher than for the control group and both groups had improved quality of life.\n The discharge planning benefited older people with hip fractures.\n A discharge planning intervention by a nurse can improve physical outcomes and quality of life in hip fracture patients." ]	The effectiveness of the provision of hip protectors in reducing the incidence of hip fracture in older people is still not clearly established, although they may reduce the rate of hip fractures if made available to frail older people in nursing care. It remains unknown from studies identified to date if these findings apply to all types of hip protectors. Some cluster-randomised trials have been associated with high risk of bias. Poor acceptance and adherence by older people offered hip protectors have been key factors contributing to the continuing uncertainty.
CD004517	[ "19628939", "17037953" ]	[ "Effect of music therapy on anxiety and depression in patients with Alzheimer's type dementia: randomised, controlled study.", "Use of preferred music to reduce emotional distress and symptom activity during radiation therapy." ]	[ "Numerous studies have indicated the value of music therapy in the management of patients with Alzheimer's disease. A recent pilot study demonstrated the feasibility and usefulness of a new music therapy technique. The aim of this controlled, randomised study was to assess the effects of this new music therapy technique on anxiety and depression in patients with mild to moderate Alzheimer-type dementia.\n This was a single-centre, comparative, controlled, randomised study, with blinded assessment of its results. The duration of follow-up was 24 weeks. The treated group (n = 15) participated in weekly sessions of individual, receptive music therapy. The musical style of the session was chosen by the patient. The validated 'U' technique was employed. The control group (n = 15) participated under the same conditions in reading sessions. The principal endpoint, measured at weeks 1, 4, 8, 16 and 24, was the level of anxiety (Hamilton Scale). Changes in the depression score (Geriatric Depression Scale) were also analyzed as a secondary endpoint.\n Significant improvements in anxiety (p < 0.01) and depression (p < 0.01) were observed in the music therapy group as from week 4 and until week 16. The effect of music therapy was sustained for up to 8 weeks after the discontinuation of sessions between weeks 16 and 24 (p < 0.01).\n These results confirm the valuable effect of music therapy on anxiety and depression in patients with mild to moderate Alzheimer's disease. This new music therapy technique is simple to implement and can easily be integrated in a multidisciplinary programme for the management of Alzheimer's disease.\n Copyright 2009 S. Karger AG, Basel.", "Music therapy has decreased anxiety levels in many medical settings. This randomized clinical trial examined the effectiveness of a music listening intervention, delivered by a board-certified music therapist, in patients undergoing curative radiation therapy (RT). Emotional distress (anxiety, depression, and treatment-related distress) and symptoms (fatigue and pain) were measured at baseline, mid-treatment, and end of treatment in 63 patients undergoing RT. Although patients who listened to self-selected music reported lower anxiety and treatment-related distress, there was a decline in these outcomes for patients in both groups over the course of RT. Depression, fatigue, and pain were not appreciably affected by music therapy. Within the music group, there was a significant correlation between number of times music was used/week and the change in treatment-related distress, suggesting that higher doses of music produced greater declines in distress. While these findings provided some support for the use of music in reducing distress during RT, further research demonstrating clear differences between intervention and control conditions is needed. Physical symptoms were not affected by the use of music over the course of RT." ]	Findings from individual randomised trials suggest that music therapy is accepted by people with depression and is associated with improvements in mood. However, the small number and low methodological quality of studies mean that it is not possible to be confident about its effectiveness. High quality trials evaluating the effects of music therapy on depression are required.
CD001495	[ "9033441", "11908511", "11956046", "8103655", "8610716", "10095821", "19383058", "12564609", "9227720", "11316640", "7497762", "8681667" ]	[ "Short-term regular beta 2-adrenergic agonists treatment is safe in mild asthmatics taking low doses of inhaled steroids.", "Is the increase in bronchial responsiveness or FEV1 shortly after cessation of beta2-agonists reflecting a real deterioration of the disease in allergic asthmatic patients? A comparison between short-acting and long-acting beta2-agonists.", "Beta2-agonist tolerance and exercise-induced bronchospasm.", "Asthma control during and after cessation of regular beta 2-agonist treatment.", "Addition of anticholinergic solution prolongs bronchodilator effect of beta 2 agonists in patients with chronic obstructive pulmonary disease.", "The response to inhaled and oral steroids in patients with stable chronic obstructive pulmonary disease.", "Cardio-selective and non-selective beta-blockers in chronic obstructive pulmonary disease: effects on bronchodilator response and exercise.", "Symptoms are an important outcome in chronic obstructive pulmonary disease clinical trials: results of a 3-month comparative study using the Breathlessness, Cough and Sputum Scale (BCSS).", "Effects of the long acting beta agonist formoterol on asthma control in asthmatic patients using inhaled corticosteroids. The Netherlands and Canadian Formoterol Study Investigators.", "Use of a long-acting inhaled beta2-adrenergic agonist, salmeterol xinafoate, in patients with chronic obstructive pulmonary disease.", "Inhaled budesonide therapy for patients with stable COPD.", "Extended therapy with ipratropium is associated with improved lung function in patients with COPD. A retrospective analysis of data from seven clinical trials." ]	[ "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.", "Regular use of beta2-agonists might result in increased bronchial hyper-responsiveness (BHR) and decreased forced expiratory volume in 1 sec (FEV1). It has been suggested that these possible detrimental effects are not a real deterioration of the disease, but that it might be only a transient (rebound) effect shortly after discontinuing this regular use. Moreover, these effects are thought to occur especially during short-acting and not during long-acting beta2-agonists use. The aim of this study was to invest gate whether a rebound effect (a pharmacological deterioration effect diminishing after several hours) in FEV1 and PC20 (concentration of histamine causing a 20% fall in FEV1 with regard to baseline) occurred after cessation of regular use of beta2-agonists, and whether this occurred both after short-acting and long-acting beta2-agonists. Allergic asthmatic patients (n = 134) were randomly allocated to the use of a short-acting (salbutamol), a long-acting beta2-agonist (formoterol) or placebo for 12 weeks (double-blind, double-dummy). No other asthma medication was allowed, including inhaled corticosteroids. At the start and every 4 weeks later FEV and PC20 were measured, each time at least 12 h after the last doses of study medication, which is in the possible rebound period. To investigate whether a (transient) rebound effect occurred, parameters were additionally measured at least 72 h later after discontinuation of the study medication. After 12 weeks of short-acting beta2-agonist use, a drop was seen in FEV1 from 85.6 (+/- 2.21)% predicted to 78.8 (+/- 2.9)% predicted, measured 15 h (median) after the last doses of medication. This was significantly different compared to placebo. When measured 168 h (median) later FEV1 recovered to 85.5 (+/- 2.4)% predicted, comparable to baseline. PC20 decreased with -1.17 (+/- 0.44) doubling dose after 12 weeks of short-acting beta2-agonist use, measured 15 h after the last doses of medication, which was significantly different compared to placebo. However, 168 h later PC20 recovered slightly with +0.55 (+/- 0.34) doubling dose, but this value was still lower compared to placebo. In contrast, during long-acting beta2-agonist and placebo use no significant changes were seen. In conclusion, the use of short-acting beta2-agonists resulted in a transient (rebound) effect in FEV while the effects on PC20 may point to a real deterioration of the disease. Long-acting beta2-agonist and placebo use showed no changes. We conclude that a mono-therapy of short-acting and not of long-acting beta2-agonists might have deleterious effects in asthma.", "The effect of regular inhaled beta-agonist on the treatment of exercise-induced bronchoconstriction was studied. Eight subjects with exercise-induced bronchoconstriction took 1 week each of salbutamol 200 microg qid or placebo in a random-order, double-blind, crossover study. They then withheld this treatment for 8 hours before performing a dry-air, sub-maximal exercise challenge at a work-rate previously shown to induce a 15% fall in forced expiratory volume in 1 second (FEV1). Five minutes after exercise, they inhaled salbutamol 100, 100, and 200 microg at 5-minute intervals. The mean pre-exercise FEV1 was similar on both study days. However, pretreatment for 1 week with salbutamol led to a significantly greater fall in FEV1 after exercise. The FEV1 remained lower than during the placebo arm despite the administration of salbutamol after exercise. This difference persisted 25 minutes after exercise. It is concluded that regular beta-agonist treatment leads to increased exercise-induced bronchoconstriction and a suboptimal bronchodilator response to beta-agonist. The data suggest that previous regular beta-agonist treatment may lead to a failure to respond to emergency bronchodilator treatment during an acute asthma attack and support current opinion that regular short-acting beta-agonist therapy should not be used to treat asthma.", "It has been suggested that regular treatment with high doses of beta 2-agonists might result in poorer control of asthma and increased bronchial responsiveness. We have examined change in FEV1 (delta FEV1), bronchial reactivity, peak expiratory flow (PEF), and symptoms during and after 3 wk of regular treatment with a relatively low dose of albuterol and broxaterol, a new beta 2-agonist. Eleven subjects 18 to 50 yr of age with mild asthma inhaled albuterol (200 micrograms), broxaterol (400 micrograms), or placebo three times a day for 3 wk with a 2- to 4-wk run-in/washout period between treatments. Ipratropium bromide was allowed for symptomatic relief. The PD20 (dose of histamine causing a 20% fall in FEV1) was measured before and 11, 35, and 59 h after cessation of treatment and a bronchodilator dose-response study before and 83 h after cessation of treatment. Change from baseline after albuterol and broxaterol are compared with change after placebo. Diurnal change in PEF (amplitude % mean) increased during treatment with albuterol by 6.5% (95% CI, 1.7-12.3; p < 0.02) mainly because of a fall in morning PEF. Cessation of treatment with both beta 2-agonists was associated with a fall in FEV1 and PD20 compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)", "A randomized, double-blind placebo-controlled clinical trial was designed to assess the safety, efficacy, and duration of the bronchodilation resulting from the addition of 500 micrograms of ipratropium bromide (Atrovent; Boehringer Ingelheim, CT) inhalation solution to standard small volume nebulizer treatments with 2.5 mg albuterol inhalation solution. A total of 195 patients (63% men, average age 64 years) with > 10 pack-year smoking histories and stable, moderate-to- severe chronic obstructive pulmonary disease (COPD; forced expiratory volume in 1 second [FEV1] 1.02 liter, 38.8% predicted) from eight university-affiliated chest clinics in seven U.S. cities were enrolled into the study. Asthma, rhinitis, and eosinophilia were exclusions, as was daily use of > 10 mg of prednisone (or 20 mg on alternate days). There was a 2-week stabilization period during which the patients were instructed in the use of the small volume nebulizers, which they used three times daily with albuterol alone. They were asked to keep daily logs of peak flow rates, pulmonary symptoms, and additional medication usage. On their test day 1 the subjects came to the pulmonary function laboratory having been off theophylline for 24 hours and beta 2-agonists for 12 hours and performed a baseline spirometry. They then received their morning small volume nebulizer treatment of albuterol to which was added either 500 micrograms if ipratropium bromide or a saline placebo. Spirometry was repeated at 15, 30, and 60 minutes, and then hourly for 8 hours. Subjects then took home a 2-week supply of albuterol and test drug for thrice daily use in their small volume nebulizer. They were evaluated for pulmonary symptoms and adverse effects every 14 days. The 8-hour spirometry was repeated on test day 43 and finally on test day 85. Primary data evaluated were the peak increase in FEV1 and the area between the FEV1 baseline value and the 8-hour FEV1 curve. Similar calculations were made for forced vital capacity (FVC) and 25-75% forced expiratory flow (FEF25-75%). On test day 1 the peak increase in FEV1 for the ipratropium bromide + albuterol subjects was 26% greater than those on placebo + albuterol (p < 0.003). The area under the 8-hour FEV1 curve was 64% greater in those given ipratropium bromide on test day 1 (p < 0.0002). Similar increases were seen in FVC and FEF25-75%. The peak improvements in FEV1 and FVC with the addition of ipratropium bromide to albuterol were maintained on test days 43 and 85. Considering the safety and efficacy profiles of this combination, the data would suggest that ipratropium bromide inhalation solution should be considered first-line therapy for those patients with COPD requiring small volume nebulizer treatments.", "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.", "Patients with chronic obstructive pulmonary disease (COPD) often have co-existing cardiovascular disease and may require beta-blocker treatment. There are limited data on the effects of beta-blockers on the response to inhaled beta2-agonists and exercise capacity in patients with COPD.\n To determine the effects of different doses of cardio-selective and non-selective beta-blockers on the acute bronchodilator response to beta-agonists in COPD, and to assess their effects on exercise capacity.\n A double-blind, randomized, three-way cross-over (metoprolol 95 mg, propranolol 80 mg, placebo) study with a final open-label high-dose arm (metoprolol 190 mg). After 1 week of each treatment, the bronchodilator response to salbutamol was measured after first inducing bronchoconstriction using methacholine. Exercise capacity was assessed using the incremental shuttle walk test.\n Eleven patients with moderate COPD were recruited. Treatments were well-tolerated although two did not participate in the high-dose metoprolol phase. The area under the salbutamol-response curve was lower after propranolol compared with placebo (P=0.0006). The area under the curve also tended to be lower after high-dose metoprolol (P=0.076). The per cent recovery of the methacholine-induced fall was also lower after high-dose metoprolol (P=0.0018). Low-dose metoprolol did not alter the bronchodilator response. Oxygen saturation at peak exercise was lower with all beta-blocker treatments (P=0.046).\n Non-selective beta-blockers and high doses of cardio-selective beta-blockers may inhibit the bronchodilator response to beta2-agonists in patients with COPD. Beta-blockers were also associated with lower oxygen saturation during exercise. The clinical significance of these adverse effects is uncertain in view of the benefits of beta-blocker treatment for cardiovascular disease.", "The need to manage the key symptoms of chronic obstructive pulmonary disease (COPD) (breathlessness, cough and sputum) is an important treatment objective. Viozan (sibenadet HCl, AR-C68397AA) is a novel dual D2 dopamine receptor, beta2-adrenoceptor agonist, which combines conventional bronchodilatory activity with the sensory nerve modulation afforded by dopamine agonism. The efficacy of this agent in relieving patient symptoms has been determined in a series of large-scale clinical studies; the results of a 3-month, placebo-controlled multi-centre study are reported. Effect on patient symptoms was determined using a novel patient-reported assessment instrument, the Breathlessness, Cough and Sputum Scale (BCSS). Patients with smoking-related COPD were required to complete a 2-week baseline period before being randomized to one of three treatment groups; sibenadet (500 microg three times daily) plus placebo (twice daily); salmeterol (50 microg twice daily) plus placebo (three times daily); placebo (twice daily) plus a second placebo (three times daily). All treatments were delivered via pressurized metered dose inhaler (pMDI) for 12 weeks. From enrolment, patients were required to complete daily diary cards to record symptoms of breathlessness, cough and sputum, medication use and adverse events. The primary outcome measure was the difference between the mean BCSS total score measured over the baseline period and the mean BCSS total score in the final 4 weeks of the treatment period. Secondary measures included assessment of lung function, rescue medication use, exacerbations, health-related quality of life, opinion of efficacy and safety. Although an initial reduction in BCSS total score (indicating symptom improvement) was seen with sibenadet therapy, this effect was not maintained for the study duration. Salmeterol therapy, however, resulted in a sustained reduction in BCSS total score. No notable benefit over placebo was seen in lung function, exacerbations or health-related quality of life with either active treatment. While the results of this study failed to demonstrate sustained efficacy with sibenadet therapy, they do indicate the value of symptom assessment in the clinical evaluation of new drugs for the treatment of COPD.", "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.", "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.", "A significant minority of patients with COPD have favorable 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. We hypothesized that treatment with high-dose inhaled budesonide would improve clinical symptoms and pulmonary function in subjects with COPD, and that the response to inhaled beta 2-agonist will serve to individualize steroid responders. We compared a 6-week course of 800 micrograms/d inhaled budesonide with placebo, separated by 4 weeks when no medication was taken, in a double-blind crossover trial, in 8 patients responding to inhaled beta 2-agonist, and in 22 nonresponders with stable COPD. In six of eight \"responders to beta 2-agonist,\" there was a significant improvement in the FEV1 (defined as > or = 20%) following inhaled budesonide, as compared with placebo. In the 22 \"nonresponders to beta 2-agonist,\" there was no significant improvement in the mean FEV1 (1.41 +/- 0.1 L before, and 1.61 +/- 0.1 L after treatment) with inhaled budesonide or placebo. Over the 6-week course of treatment by either budesonide or placebo, the nonresponders reported similar beta 2-agonist consumption (4.8 +/- 0.2 and 5.0 +/- 0.1 puffs per patient per day, respectively). However, there was a significant difference between the two periods of treatment in the responders as for the mean daily number of beta 2-agonist inhalations (2.4 +/- 0.1 in the budesonide period as compared with 5.3 +/- 0.1 in the placebo period; p < 0.005). We conclude that treatment with inhaled steroids improved spirometry data and inhaled beta 2-agonist consumption in about 25% of patients with stable COPD, and this rate is increased to about 75% in patients who respond to beta 2-agonist inhalation.", "Bronchodilators are routinely used in the long-term therapy of patients with COPD. These drugs are generally evaluated for their short-term bronchodilatory effects. Long-term and short-term benefits, however, are not necessarily equivalent. We evaluated, therefore, the effects of extended therapy with inhaled bronchodilators in patients with COPD.\n Data were obtained from seven clinical trials in which ipratropium was compared with a beta-agonist over a 90-day treatment interval. This comprised all the available data from clinical trials performed for registration of ipratropium and included 1,445 evaluable patients. Results of pulmonary function tests were evaluated prior to and after short-term administration of bronchodilator both before and after the 90-day treatment period. In addition, data were analyzed after stratification for smoking status and for lung function.\n Long-term therapy with ipratropium resulted in improvement in baseline (ie, before short-term administration of bronchodilator) FEV1 (28 mL; p < 0.01) and FVC (131 mL; p < 0.01), while long-term therapy with beta-agonist resulted in no significant change in FEV1 (1-mL decline; p > 0.2) or in FVC (20-mL improvement; p > 0.2). The improvement in baseline function in the ipratropium-treated patients was most marked in ex-smokers (average duration of abstinence, 9 years). Short-term administration of ipratropium following the 90-day treatment interval resulted in similar response in average FEV1 (6 mL more improvement after the extended therapy; p > 0.2) and an increased response in average FVC (44 mL more improvement after extended therapy; p < 0.01). In contrast, extended therapy with beta-agonist resulted in significantly less response to the short-term administration of beta-agonist for both FEV1 (49 mL less response; p < 0.0001) and FVC (74 mL less response; p < 0.0001). Assessed as the percentage of patients who achieved a 15% improvement in lung function, most patients responded to both treatments both before and after extended therapy. There was, however, a significant decline in the number of patients who responded after extended therapy, and this was more marked for the beta-agonist treated group.\n Long-term benefits of bronchodilator therapy appear to differ from short-term effects. Extended administration of ipratropium appears to be associated with improved baseline lung function and perhaps with improvement in the response to acute bronchodilation. Extended administration of beta-agonist, in contrast, appears to have little effect on baseline lung function, but may decrease response to acute bronchodilation." ]	Use of short-acting beta-2 agonists on a regular basis for at least seven days in stable COPD is associated with improvements in post bronchodilator lung function and a decrease in breathlessness. Patients are far more likely to prefer treatment with beta-2 agonists than placebo, and less likely to drop out from such treatment. None of the studies included in this review reported sufficient data or were of sufficient length or size in order to provide reliable information on adverse effects. Therefore large scale, parallel, longer term studies would be needed to investigate the effect of treatment with regular inhaled beta-2 agonists on mortality, disease progression and side effects. Newer, long acting bronchodilators (including long-acting beta-2 agonists) are currently available and they may be more practical and/or effective in these patients. However, this review indicates that treatment with these older, inexpensive drugs is beneficial in patients with COPD.
CD001825	[ "15022802", "8938608", "15131430", "9671187", "9086543", "2527316", "7065351", "7081917", "14657746", "12678355", "7006427", "9521514", "9219134", "3056499", "711799", "3675403", "14716794", "1478809", "12496571", "1479562", "2405730", "1505264", "15589927", "776322", "9415907", "3886068", "2191752" ]	[ "No need for routine closed suction drainage in elective arthroplasty of the hip: a prospective randomized trial in 104 operations.", "Efficacy of closed wound suction drainage after single-level lumbar laminectomy.", "A randomized study of closed wound suction drainage for extensive lumbar spine surgery.", "Efficacy of surgical wound drainage in orthopaedic trauma patients: a randomized prospective trial.", "Clinical evaluation of closed suction drainage following hepatectomy.", "Prophylactic closed suction drainage of femoral wounds in patients undergoing vascular reconstruction.", "Cholecystectomy with and without drainage. A randomized, prospective study of 300 patients.", "A randomised prospective trial of two drainage methods after cholecystectomy.", "The use of postoperative subcutaneous closed suction drainage after posterior spinal fusion in adolescents with idiopathic scoliosis.", "The use of a closed-suction drain in total knee arthroplasty. A prospective, randomised study.", "Randomized trial of drainage after cholecystectomy. Suction vaersus static drainage through a main wound versus a stab incision.", "Is suction drainage necessary after total joint arthroplasty? A prospective study.", "Closed wound drainage in shoulder surgery.", "Closed suction wound drainage and lower-segment caesarean section.", "The use of suction drainage in the operation of meniscectomy.", "A randomised comparison of three drainage systems following cholecystectomy.", "Randomized clinical trial investigating the use of drains and fibrin sealant following surgery for breast cancer.", "Drainage after cholecystectomy. A prospective randomized clinical trial.", "Routine drainage is not required in reduction mammaplasty.", "Passive tube and suction drainage after elective cholecystectomy--a comparison using ultrasonography.", "Simple elective cholecystectomy: to drain or not.", "[Routine drainage following uncomplicated, elective cholecystectomy? A prospective, randomized study].", "Wound drainage versus non-drainage for proximal femoral fractures. A prospective randomised study.", "A controlled trial of drainage after cholecystectomy.", "Comparison of closed-suction drainage and no drainage after primary total knee arthroplasty.", "Suction drainage of the gallbladder bed does not prevent complications after cholecystectomy: a random control clinical trial.", "Vacuum drainage of groin wounds after vascular surgery: a controlled trial." ]	[ "The purpose of this study was to determine the utility of closed suction drainage (CSD) in elective total hip arthroplasty (THA).\n We randomized 104 elective, consecutive THAs to receive drainage (53) or no drainage (51). 60 arthroplasties were cemented and 44 hybrid.\n In the drainage group, 2 hematomas and 2 superficial wound infections occurred; there were no wound complications in the undrained group (p = 0.04). Patients receiving drainage had a greater reduction in hematocrit (10.4 vs 7.4) (p = 0.03), and longer hospital stay (5.1 days vs 4.7) (p = 0.01). At the 3-month follow-up, we found no deep wound infections in either group.\n We no longer use CSD in elective, primary, routine THA.", "The use of closed suction drainage after spinal surgery remains controversial. The purpose of this study was to determine the indications for closed suction drainage after single-level lumbar surgery. Two hundred patients who were scheduled to undergo single-level lumbar surgery without fusion were prospectively randomized into two groups. One group had a closed wound suction drain placed deep to the lumbodorsal fascia before routine closure, whereas the second group had no drain placed. Hemostasis was achieved in all patients before the surgeon had knowledge of the randomization outcome. All drains were removed on the 2nd postoperative day, and the amount of drainage was recorded. After surgery, the patients were evaluated for signs and symptoms of continued wound drainage, hematoma/seroma formation, and/or infection as well as evidence of an acquired neurologic deficit. One hundred three patients had a drain placed before closure and two patients developed postoperative wound infection, both of which were successfully treated with orally administered antibiotics. Of the 97 patients who had no drain placed after the surgical procedure, one patient developed a postoperative wound infection that was treated with surgical incision and drainage, as well as intravenously administered antibiotics. Statistical analysis revealed that the presence or absence of a drain did not affect the postoperative infection rate. No new neurologic deficits occurred in any postoperative patient. The use of drains in single-level lumbar laminectomy without fusion did not affect patient outcome. There was no significant difference in the rate of infection or wound healing and no patient developed a postoperative neurologic deficit.", "A prospective randomized study.\n To study the risk of infection, hematoma, and neurologic deficits following extensive lumbar spine surgery in patients with or without prophylactic closed wound suction drain placement.\n One randomized study assessing prophylactic drain placement in one-level lumbar spine surgery suggested that the use of a wound drain is not effective at preventing infection and may actually increase the rate of this complication. Our study was designed to determine the efficacy of closed wound suction drainage in preventing complications after extensive lumbar spine surgery.\n Eighty-three consecutive patients undergoing extensive lumbar spine surgery were prospectively randomized to one of two groups. Forty-two patients had a closed wound suction drain placed before wound closure and 41 patients did not have a drain placed. The two groups were then assessed for differences in postoperative infection rate, incidence of hematoma and neurologic deficits, operating room time, estimated blood loss, hemoglobin and hematocrit values, temperature, dressing drainage, and length of hospital stay. RESULTS.: No infections, epidural hematomas, or new neurologic deficits were encountered in either group of patients. The only significant finding was a higher temperature in the \"no drain\" group the first day after surgery (P = 0.0437).\n Based on the findings in this and other studies, the decision to use or not use a wound drain following lumbar spine surgery should be left to the surgeon's discretion.", "To study the efficacy of closed suction drainage in clean nonemergent surgical fracture fixation or bone grafting on the extremities or pelvis.\n A prospective randomized trial.\n The orthopaedic trauma service of a Level I trauma hospital.\n Patients were older than age eighteen years and undergoing clean nonemergent surgical fracture fixation or bone grafting procedures on the extremities (excluding hands and feet) or pelvis.\n The application of a surgical drain.\n Wound drainage, edema, hematoma and erythema, dehiscence, infection, and need for surgery or readmission were followed for six weeks. A univariate analysis with Student's t test for continuous variables and chi-squared analysis for all categorical data were used, with a p value of < or = 0.05 considered statistically significant.\n A total of 202 patients were randomized to 102 patients with no drain and 100 patients with a drain. There was no significant difference between the groups with regard to injury severity, systemic disease, age, body weight, physical status, or estimated blood loss. There was no significant difference between the drain and no-drain groups in any of the parameters evaluated.\n There is no significant difference between drained and nondrained wounds in clean, nonurgent orthopaedic trauma surgery. It appears that drainage systems can be safely eliminated in this group.", "A prospective randomized study on 186 patients was conducted to determine the influence of closed suction drainage (n = 102) versus open drainage (n = 84) on the incidence of postoperative complications after elective hepatic resection. The patients were randomly allocated between the two groups. A total of 60 complications occurred in 31 of the 84 patients (36.9%) given open drainage, while 24 complications occurred in 15 of the 102 patients (14.7%) given closed suction drainage. The incidence of pleural effusion, postoperative ascites, and infected subphrenic collections was significantly lower in the closed suction drainage group than in the open drainage group, at 31% vs 16% (P < 0.05), 19% vs 3% (P < 0.01), and 17% vs 5% (P < 0.05) respectively. However, both groups showed similar rates of subphrenic hematoma and bile collection. These findings indicate that closed suction drainage significantly reduces the incidence of postoperative complications after elective hepatic resection.", "Prophylactic closed suction drainage has been advocated in a variety of surgical wounds, but its use in wounds involving vascular anastomoses has not been studied. Fifty patients undergoing lower extremity revascularization that required bilateral groin incisions were randomly assigned to have either the right or left side of the groin drained with a closed suction catheter. The contralateral wound was closed without drainage. Statistically there was no difference between wound closed with drains and undrained wounds in the occurrence of hematomas, seromas, lymphoceles, superficial infections, subcutaneous infections, or graft infections; although serious complications were more frequent in the drained wounds. Prophylactic closed suction drainage appears to offer no advantage over closure without drainage in wounds of the groin resulting from elective vascular operations.", "A randomized, prospective study of 300 cholecystectomies was undertaken to evaluate the merits of drainage through a standard Penrose or Chaffin-Pratt sump tube matched against no drainage at all. There was no difference in mortality or length of hospital stay. There was, however, a significantly higher incidence of postoperative pyrexia due to atelectasis and wound infection in the drainage groups. Neither drain fulfilled its objective of providing outflow for a subhepatic collection, thus avoiding bile peritonitis. This study suggests that surgical drainage after every uncomplicated cholecystectomy is unnecessary and unwise.", "A prospective trial is described in which simple tube drainage was compared with suction drainage after cholecystectomy. Postoperative chest infection and infected or painful drain wounds were both significantly more common with simple tube drains. Postoperative discomfort was more frequent with tube drains in situ and wound infection more common in the suction group, but neither of these differences was statistically significant. The mean volume of fluid drained and duration of hospital stay did not differ between methods. It is concluded that both methods are satisfactory, but suction drainage is recommended.", "BACKGROUND The purpose of this prospective study was to assess the impact of closed suction drainage on transfusion requirements, frequency of dressing changes, and wound healing following posterior spinal fusion in adolescents with idiopathic scoliosis. METHODS Thirty patients were randomly assigned to one of two groups: drain or no drain. Although the group with drains received more postoperative autologous blood transfusions than the group with no drains (0.88 vs 0.5 unit), the difference was not statistically significant (P = 0.2131). In the undrained group, 58% of the patients had moderate to completely saturated dressings on the second postoperative day compared with only 17% of patients in the drained group. Three of 12 patients in the undrained group demonstrated a wound complication rate compared with no complications in the drained group. CONCLUSION In conclusion, subcutaneous closed suction drainage can improve immediate postoperative wound care without significantly increasing blood loss and transfusion requirements for patients undergoing surgery for idiopathic scoliosis.", "We prospectively randomised 100 patients undergoing cemented total knee replacement to receive either a single deep closed-suction drain or no drain. The total blood loss was significantly greater in those with a drain (568 ml versus 119 ml, p < 0.01; 95% CI 360 to 520) although those without lost more blood into the dressings (55 ml versus 119 ml, p < 0.01; 95% CI -70 to 10). There was no statistical difference in the postoperative swelling or pain score, or in the incidence of pyrexia, ecchymosis, time at which flexion was regained or the need for manipulation, or in the incidence of infection at a minimum of five years after surgery in the two groups. We have been unable to provide evidence to support the use of a closed-suction drain in cemented knee arthroplasty. It merely interferes with mobilisation and complicates nursing. Reinfusion drains may, however, prove to be beneficial.", "One hundred eighty-four patients who underwent biliary surgery were randomly allocated to four groups arranaed in a 2 by 2 design. In 92 patients the drain was brought out through the wound and in the other 92 through a stab incision. In half of the patients in each group the drain was connected to a suction system and in the other half to a sterile bag. Suction was found to impair rather than enhance intraperitoneal drainage. In patients who underwent elective cholecystectomy and early operation for acute cholecystitis, the amount of discharge was more than twice as large when suction was omitted than when it was applied. After common duct operations the amount of discharge was very large and there was little difference in cases with and without suction. Prolonged drainage, static or suction, resulted in an increase in the serum haptoglobin level. Analysis of out data suggested that after a few days the drain starts to act as a traumatic stimulus. No difference was found between cases with the drain brought out through a stab incision and those with the drain brought out through the main wound. A number of studies have ascertained the superiority of closed to open drainage. The results of the present trial lead us to recommend that after biliary surgery the closed us to recommend that after biliary surgery the closed drain should not be connected to a suction apparatus and that after elective cholecystectomy the drain should preferably be removed after a few days.", "A prospective evaluation of 98 patients who had undergone a total hip or knee arthroplasty was conducted to assess the effect of postoperative suction drainage. Sixty-six patients undergoing elective total hip arthroplasty and 32 patients undergoing total knee replacement were randomly allocated to undergo either suction drainage or no drainage of the wound. Statistical analysis of the results showed no difference in wound healing, severity of wound haematoma, postoperative blood transfusion requirement, range of motion and duration of the hospitalization between the two groups. We conclude that the use of closed suction drainage provides no apparent advantage after uncomplicated total hip or knee arthroplasty.", "To evaluate the effectiveness of closed wound drainage in shoulder surgery, 300 patients were enrolled in a prospective randomized study. Three operations were studied: rotator cuff repair, anterior reconstruction for instability, and arthroplasty. One hundred patients were included in each group. All patients were evaluated for wound hematoma, infection, variation in postoperative rehabilitation caused by wound problems, and length of hospital stay. No statistical difference was found between the patients whose wounds were drained and those whose wounds were not drained. This finding existed within each category. Our data do not support the routine use of closed wound drainage in elective shoulder surgery.", "In a randomized controlled study of wound suction drainage after transverse suprapubic incision for lower-segment caesarean section no significant advantages could be demonstrated for routine drainage in terms of wound infection, haematoma formation, duration of hospital stay or analgesic requirements.", "A prospective trial has been carried out to determine the value of suction drainage in the operation of meniscectomy. One hundred operations were analysed, in half of which drains had been used. The use of the drain could not be shown to result in any sustained advantages. The demand for analgesics after the operation was reduced but not to a statistically significant level. The size of the early effusion was significantly reduced, but this benefit was lost when the knee was mobilised. The return of power to the quadriceps and of movement to the knee were not hastened. The average volume of fluid drained was 134 millilitres and it has been shown that forty-eight hours is a suitable time for removal of the drain. The use of suction drainage is not advocated for the uncomplicated operation of meniscectomy.", "The efficacy of low pressure, high pressure and passive drainage systems have been compared after cholecystectomy. Symptoms of pain, discomfort and nausea were compared using linear analogue scales and spirometry was used to examine pre-operative and postoperative respiratory function. The low pressure suction drain removed an intraperitoneal marker, gentamicin, more effectively than the high pressure suction drain, but not more effectively than the passive drain. There were no differences in postoperative respiratory function nor in the amount of pain or discomfort between the groups. The passive drain group reported less nausea than the suction drain groups. If a negative pressure drainage system is to be used, a low pressure suction drain should be used in preference to a high pressure system.", "Despite limited evidence, closed suction drainage is often used to reduce the risk of seroma formation after breast cancer surgery. The aim of this study was to evaluate the effect of drains and fibrin sealant on the incidence of seroma formation.\n A total of 116 patients undergoing surgery for breast cancer were randomized to receive suction drainage (group 1; n = 58), or to receive no drain (n = 58). Patients allocated to receive no drain were further randomized to have fibrin sealant applied to the dissected area (group 2; n = 29), or to no intervention (group 3; n = 29). Outcome measures were incidence and volume of postoperative seroma, length of hospital stay and postoperative pain scores.\n There was no significant difference in the incidence of seroma between group 1 (15 of 58) and either group with no drains (ten of 29 in group 2; 12 of 29 in group 3). There was a significant reduction in hospital stay and postoperative pain scores in patients who did not have a drain. Following mastectomy without a drain, the use of fibrin sealant was associated with a significant reduction in the incidence and total volume of seroma (190 versus 395 ml; P = 0.012).\n Drains did not prevent seroma formation, and were associated with a longer postoperative stay and higher pain scores after surgery for breast cancer. In patients who had mastectomy the use of fibrin sealant reduced the rate of seroma formation.\n Copyright 2004 British Journal of Surgery Society Ltd.", "This prospective clinical study was done to assess the efficacy of postcholecystectomy drainage. A total of 173 cholecystectomized patients were randomized into two groups; group A (86 patients) without drainage and group B (87 patients) with drainage. Group B included two types of patients; B1 (52 patients) with suction drain and B2 (35 patients) with gravity drain. Evidence of wound infection, chest complications, and duration of hospital stay were recorded in every case. Ninety five patients were assessed for chest complications and subhepatic collection by chest x-ray and abdominal ultrasonography. In group B patients the total amount of fluid drained was measured. The results were analysed by appropriate statistical methods. There was no significant difference in the rate of wound infection or atelectasis in either group, although there was apparent increase of lung complications and subhepatic collections in Group B1. The average postoperative hospital stay was significantly increased in group B patients. Considering all the parameters of this study, it was found that drainage with gravity was attended with the least morbidity.", "To date, there have been no randomized trials documenting the efficacy of closed suction drainage when applied to reduction mammaplasty. Despite this, it has become the standard of care. A recent retrospective review suggests that closed suction drainage is not necessary. This study attempts to resolve this issue in a prospective, randomized fashion. The Institutional Review Board of the College of Medicine of The Pennsylvania State University approved the study. Forty-nine consecutive patients who underwent reduction mammaplasty by the inferior pedicled techniques were enrolled. Each patient was randomized to having a drain in either the right or left breast. The other breast was undrained. Patients were followed up for rate of complications and for patient satisfaction. Their ages ranged from 17 to 62 years, with a mean of 33 years. Weight of reduction from the drained breasts ranged from 360 to 1090 g, with a mean reduction of 675 g. Weight of reduction from the undrained group ranged from 380 to 1011 g, with a mean of 620 g. There were a total of 11 complications in the study. In the drained group, there were six complications out of 49 breasts (partial nipple loss in one, minor wound breakdown in two, fat necrosis in two, and hematoma in one). In the undrained group, there were five complications out of 49 breasts (partial nipple loss in none, minor wound breakdown in three, fat necrosis in one, and hematoma in one). Statistical analysis using the McNemar test revealed no significant difference between the two groups. A questionnaire revealed that the patients preferred the increased early postoperative comfort afforded by the absence of a drain. Performing reduction mammaplasty without the use of closed suction drainage is safe and is preferred by the patients.", "Daily ultrasonography of the gallbladder bed was performed in patients with suction or passive tube drains after elective cholecystectomy. A total of 19 patients was randomized to suction drainage and 17 to passive tube drainage. A policy of early drain removal was followed. No significant difference was found between the volume drained and the size of collection detected in either group. Significant bile leaks were detected and were adequately drained by suction and passive tube drains. There were no complications from drains. In view of these findings, we advocate short-term drainage of the gallbladder bed after both open and laparoscopic cholecystectomy using the drain of the surgeon's choice.", "We performed a large single-center prospective randomized controlled study to assess the role of peritoneal drainage in simple elective cholecystectomy. In 248 patients, drains were omitted; 122 patients had closed suction drains and 124 had Penrose drains. There were no deaths, and no patient required reoperation or drainage of a subhepatic collection. Wound infections occurred in eight patients with drains and in six patients without. Most infections were staphylococcal. Postoperative pulmonary complications and hospital stays were similar in patients with and without drains. Statistical analysis of the 10 available prospective controlled randomized studies (1,920 patients) by the method of odds ratios supported our findings. Simple elective cholecystectomy is safe without peritoneal drainage, but short-term drains do not increase morbidity.", "A prospective randomized and controlled study of prophylactic drainage after simple, elective cholecystectomy was carried out. From March 1988 to June 1991 80 patients received an Easy-Flow drain and 80 did not. Operation and perioperative management were standardized. The endpoint of the study was postoperative morbidity, especially postoperative pyrexia and subhepatic fluid collection. The latter was identified by ultrasonography performed daily on postoperative day 1-4. No patient died. The morbidity including postoperative pyrexia revealed no difference between drained and undrained patients. In 19 of the patients with (23.8%) and in 25 of the patients without drainage (31.3%) a subhepatic fluid collection could be demonstrated by ultrasonography. This difference was not statistically significant either. We conclude that prophylactic drainage after elective, simple cholecystectomy is of no use for the patient. As subhepatic fluid collections can be seen in drained as well as in undrained patients it has to be accepted that drainage does not guarantee the removal of subhepatic fluid. Therefore its indicatory function (bleeding) and the ability to prevent the patient having biliary peritonitis or local abscess has to be put in doubt.", "The purpose of this prospective randomised study was to examine whether routine drainage in surgery for traumatic hip fractures is useful.\n At the end of surgery for hip fractures, 200 consecutive patients (51 men, 149 women) were randomised to receive suction drainage or not. The status of wound healing was evaluated, with specific reference to haematoma formation or wound infection. Indices of blood loss were the average blood loss during operation, a decrease in the haemoglobin level, fluid collected by the drain, and blood transfusion.\n The severity of wound haematoma and the number of wound infections was not significantly different between the two groups. The average blood loss during operation was 172 ml in the drainage group and 179 ml in the non-drainage group. The volume of drainage fluid was 146 ml. The haemoglobin concentration decreased by 1.4 mg/dl in the drainage group and by 1.3 mg/dl in the non-drainage group (P = 0.83). During admission, 55 patients in the drainage group received 2.5 units of blood and 50 patients in the non-drainage group received 2.7 units.\n The severity of wound haematoma does not lead to statistically significant differences in wound infection rate. The routine use of suction drains may not prevent wound infections.", "A prospective controlled trial of drainage after cholecystectomy has been carried out. In a consecutive series of 143 patients undergoing cholecystectomy, 50 patients were randomly allocated to a drainage group and a further 50 patients to a non-drainage group. The remaining 43 patients were drained electively because the common bile duct was explored or because of infection or incomplete haemostasis. There was no significant difference in the incidence of wound infection or other complications between the drainage and the non-drainage groups. The duration of postoperative pyrexia, the number of analgesic injections and the length of postoperative hospital stay were the same in both the randomized groups. One patient in the randomized drainage group had a reactionary haemorrhage from the drain site requiring transfusion. There was no mortality but one patient in the elective drainage group had to be re-explored for a subhepatic abscess. Three patients in this group drained bile from the drain for 3-9 days but all had a T tube in place. This trial fails to demonstrate any advantage or disadvantage in draining the gallbladder bed after cholecystectomy.", "One hundred thirty-six primary total knee arthroplasty patients were randomized for the use of closed-suction, nonreinfusable wound drains. Blood loss was identical in the drained and undrained groups. Forty percent of undrained wounds compared with 0% of drained wounds required dressing reinforcement. Sixty-nine percent of undrained wounds compared with 39% of drained wounds developed ecchymosis, measuring 92 cm2 in the undrained group and 28 cm2 in the drained group. This study concludes that a simple wound drain effectively minimizes the undesirable accumulation of blood in the surrounding soft tissues and the postoperative wound dressing after total knee arthroplasty.", "Some surgeons drain the gallbladder bed routinely, some selectively and some not at all. We aimed to clarify this confusion by entering 155 consecutive patients undergoing emergency and elective cholecystectomy without exploration of the common bile duct into a random control clinical trial. In 78 patients a 3 mm suction drain was left in the gallbladder bed and in 77 the abdomen was closed without drainage. There were no withdrawals, one death (in the drainage group) from myocardial infarction and one intraperitoneal abscess complicating postoperative pancreatitis (in the no-drainage group). Other events studied were postoperative pyrexia, wound infection, respiratory tract infection and duration of hospital stay. In none of these did the two groups differ either clinically or statistically. We conclude that drainage or non-drainage of the gallbladder bed must remain a matter of individual preference.", "A pilot study of 100 consecutive groin wounds after vascular surgery demonstrated lymph leaks in 12 per cent. Lymph leak was significantly associated with wound infection and with prolongation of in-patient stay. A controlled trial was therefore instituted to assess the influence of vacuum drainage in groin wound healing. One hundred and twenty-seven wounds were randomized to drainage (n = 65) or no drainage (n = 62) and the wounds were examined 'blind' by independent observers. No difference in the incidence of lymph leakage or wound infection was noted between the two groups. The routine use of suction drainage for groin wounds in vascular surgery is unnecessary." ]	There is insufficient evidence from randomised trials to support the routine use of closed suction drainage in orthopaedic surgery. Further randomised trials with larger patient numbers are required for different operations before definite conclusions can be made for all types of orthopaedic operations.
CD001544	[ "20433721", "12616120", "18156032", "15981065", "17394048", "11433088", "8044619", "15781794", "21037443", "16491463", "15786427", "2658880", "12098743", "12004217" ]	[ "Colon and rectal surgery for cancer without mechanical bowel preparation: one-center randomized prospective trial.", "Colon and rectal surgery without mechanical bowel preparation: a randomized prospective trial.", "Mechanical bowel preparation for elective colorectal surgery: a multicentre randomised trial.", "Mechanical bowel preparation or not? Outcome of a multicenter, randomized trial in elective open colon surgery.", "Mechanical bowel preparation for elective colorectal surgery with primary intraperitoneal anastomosis by a single surgeon: interim analysis of a prospective single-blinded randomized trial.", "The effect of anorectal manometry on the outcome of treatment in severe childhood constipation: a randomized, controlled trial.", "Requirement for bowel preparation in colorectal surgery.", "Is mechanical bowel preparation mandatory for elective colon surgery? A prospective randomized study.", "Rectal cancer surgery with or without bowel preparation: The French GRECCAR III multicenter single-blinded randomized trial.", "Randomized clinical trial of bowel preparation with a single phosphate enema or polyethylene glycol before elective colorectal surgery.", "Randomized clinical trial of mechanical bowel preparation versus no preparation before elective left-sided colorectal surgery.", "Elective colon and rectal surgery without nasogastric decompression. A prospective, randomized trial.", "[Mechanical preparation in elective colorectal surgery, a usual practice or a necessity?].", "Neorectal reservoir is not the functional principle of the colonic J-pouch: the volume of a short colonic J-pouch does not differ from a straight coloanal anastomosis." ]	[ "Mechanical bowel preparation is routinely done before colon and rectal surgery, aimed at reducing the risk of postoperative infectious complications. The aim of the study was to assess whether elective colon and rectal surgery can be safely performed without preoperative mechanical bowel preparation.\n Patients undergoing elective colon and rectal resections with primary anastomosis were prospectively randomized into two groups. Group A had mechanical bowel preparation with polyethylene glycol before surgery, and group B had their surgery without preoperative mechanical bowel preparation. Patients were followed up for 30 days for wound, anastomotic, and intra-abdominal infectious complications.\n Two hundred forty four patients were included in the study, 120 in group A and 124 in group B. Demographic characteristics, type of surgical procedure and type of anastomosis did not significantly differ between the two groups. There was no difference in the rate of surgical infectious complications between the two groups but the overall infectious complications rate was 20.0% in group A and 11.3% in group B (p .05). Wound infection (p = 0.18), anastomotic leak (p = 0.52), and intra-abdominal abscess (p = 0.36) occurred in 9.2%, 5.8%, and 5.0% versus 4.8%, 4.0%, and 2.4%, respectively. No mechanical bowel preparation seems to be safe also in rectal surgery.\n These results suggest that elective colon and rectal surgery may be safely performed without mechanical preparation.", "To assess whether elective colon and rectal surgery can be safely performed without preoperative mechanical bowel preparation.\n Mechanical bowel preparation is routinely done before colon and rectal surgery, aimed at reducing the risk of postoperative infectious complications. However, in cases of penetrating colon trauma, primary colonic anastomosis has proven to be safe even though the bowel is not prepared.\n Patients undergoing elective colon and rectal resections with primary anastomosis were prospectively randomized into two groups. Group A had mechanical bowel preparation with polyethylene glycol before surgery, and group B had their surgery without preoperative mechanical bowel preparation. Patients were followed up for 30 days for wound, anastomotic, and intra-abdominal infectious complications.\n Three hundred eighty patients were included in the study, 187 in group A and 193 in group B. Demographic characteristics, indications for surgery, and type of surgical procedure did not significantly differ between the two groups. Colo-colonic or colorectal anastomosis was performed in 63% of the patients in group A and 66% in group B. There was no difference in the rate of surgical infectious complications between the two groups. The overall infectious complications rate was 10.2% in group A and 8.8% in group B. Wound infection, anastomotic leak, and intra-abdominal abscess occurred in 6.4%, 3.7%, and 1.1% versus 5.7%, 2.1%, and 1%, respectively.\n These results suggest that elective colon and rectal surgery may be safely performed without mechanical preparation.", "Mechanical bowel preparation is a common practice before elective colorectal surgery. We aimed to compare the rate of anastomotic leakage after elective colorectal resections and primary anastomoses between patients who did or did not have mechanical bowel preparation.\n We did a multicentre randomised non-inferiority study at 13 hospitals. We randomly assigned 1431 patients who were going to have elective colorectal surgery to either receive mechanical bowel preparation or not. Patients who did not have mechanical bowel preparation had a normal meal on the day before the operation. Those who did were given a fluid diet, and mechanical bowel preparation with either polyethylene glycol or sodium phosphate. The primary endpoint was anastomotic leakage, and the study was designed to test the hypothesis that patients who are given mechanical bowel preparation before colorectal surgery do not have a lower risk of anastomotic leakage than those who are not. The median follow-up was 24 days (IQR 17-34). We analysed patients who were treated as per protocol. This study is registered with ClinicalTrials.gov, number NCT00288496.\n 77 patients were excluded: 46 who did not have a bowel resection; 21 because of missing outcome data; and 10 who withdrew, cancelled, or were excluded for other reasons. The rate of anastomotic leakage did not differ between both groups: 32/670 (4.8%) patients who had mechanical bowel preparation and 37/684 (5.4%) in those who did not (difference 0.6%, 95% CI -1.7% to 2.9%, p=0.69). Patients who had mechanical bowel preparation had fewer abscesses after anastomotic leakage than those who did not (2/670 [0.3%] vs 17/684 [2.5%], p=0.001). Other septic complications, fascia dehiscence, and mortality did not differ between groups.\n We advise that mechanical bowel preparation before elective colorectal surgery can safely be abandoned.", "Mechanical bowel preparation is common practice in elective colon surgery. In recent literature the value of this procedure is under discussion. To verify the value of mechanical bowel preparation in elective open colon surgery, a randomized clinical trial was conducted.\n During a prospective, multicenter, randomized study, 250 patients undergoing elective open colon surgery were randomized between receiving mechanical bowel preparation with polyethylene glycol (PEG group, 125 patients) and having a normal meal preoperatively (normal meal preoperatively group, 125 patients). Outcome parameters were wound infection with bacterial results of intraoperative swabs and anastomotic leak.\n In the polyethylene glycol group there were a total of nine wound infections (7.2 percent) and seven anastomotic leaks (5.6 percent) compared with seven wound infections (5.6 percent) (P = 0.61) and six anastomotic leaks (4.8 percent) (P = 0.78) in the normal meal preoperatively group. Bacterial results showed 52 percent sterile subcutis swabs in the PEG group and 63 percent sterile subcutis swabs in the normal meal preoperatively group (P = 0.11).\n In the present study we could not detect a difference in outcome parameters between patients receiving mechanical bowel preparation in elective open colon surgery and patients without preoperative treatment of the bowel. The present study, although underpowered, did not show a difference in the primary outcome of bacterial wound cultures between patients receiving preoperative mechanical bowel preparation and patients receiving no preoperative bowel treatment. We conclude that there may be no need to continue the use of mechanical bowel preparation in elective open colon surgery.", "We report an interim analysis of a prospective single-blinded randomized trial designed to investigate whether preoperative mechanical bowel preparation influences the rate of surgical-site infection and anastomotic failure after elective colorectal surgery with primary intraperitoneal anastomosis performed by a single surgeon. Patients scheduled to undergo an elective colorectal procedure with a primary intraperitoneal anastomosis were randomized to receive either oral polyethylene glycol lavage solution and enemas (group A) or no preparation (group B). Surgical-site infection and anastomotic failure were investigated. Of 97 patients included, 48 were assigned to group A and 49 to group B. Twelve (12.4%) developed wound infections, six in each group (12.5 vs. 12.2%; NS). Intra-abdominal sepsis was only seen in group A (n = 3, 6.3%). Anastomotic failure occurred in four patients in group A (8.3%) vs. two patients in group B (4.1%) (NS). The overall complication rate in group A was 27.1%, vs. 16.3% in group B. The number needed to harm was 9.3. Our interim analysis of a prospective single-blinded randomized trial suggests that a surgeon may have the same or even worse outcomes when mechanical bowel preparation is routinely used for colorectal surgery with primary intraperitoneal anastomosis.", "Approximately 50% of constipated children contract rather than relax the external sphincter complex during a defecation attempt. Although biofeedback training (BF) is able to change this defecation behavior, there is no additional effect of BF to conventional treatment (CT) on clinical outcome compared with CT alone. It has been postulated that the absence of a significant difference between these 2 treatment options might be because of a therapeutic, \"demystifying\" effect of performing anorectal manometry in conventionally treated children, necessary to obtain basal manometric data. The objective of this prospective, controlled, randomized study was to evaluate the effect of CT with 2 anorectal manometry sessions compared with CT alone (dietary advice, diary, toilet training, oral laxatives, and enemas) on clinical outcome.\n A total of 212 constipated children (143 boys) who were visiting a referral pediatric gastroenterologic practice were randomized prospectively to CT alone (115 patients) or to CT combined with 2 manometry sessions (CTM; 97 patients). Patients were included in the study when they fulfilled at least 2 of the 4 following criteria: stool frequency fewer than 3 per week, 2 or more soiling and/or encopresis episodes per week, periodic passage of very large amounts of stool every 7 to 30 days, or a palpable rectal or abdominal fecal mass. CT comprises dietary advice, a daily diary, toilet training, and oral laxative treatment preceded by rectal disimpaction with enemas on 3 consecutive days. During both manometries, the child and the parent could watch the tracing on the computer screen. No explanation was given to either the child or the parents during the procedure. When the procedure was finished, the tracings were clarified. Successful treatment was defined as a defecation frequency of 3 or more per week and fewer than 1 soiling/encopresis episode per 2 weeks and no use of laxatives.\n Only 4 and 2 children from the CT and CTM groups showed no soiling and/or encopresis, whereas 76% and 65%, respectively, reported the periodic passage of large stools. In 26% and 30% of the patients, a rectal scybalum was found on physical examination. The success rates at 6, 26, 52, and 104 weeks' follow-up were 4%, 24%, 32%, and 43% and 7%, 22%, 30%, and 35% in the CT and CTM group, respectively. No significant difference in success percentage was observed between the 2 groups at any time of follow-up with relative risks (CT/CTM) and 95% confidence intervals, respectively, of 0.55 (0.16-1.89), 1.13 (0.67-1.89), 1.07 (0.69-1.65), and 1.23 (0.81-1.85). A significant increase in defecation frequency was observed between the first (intake) and second visits, which was sustained at all subsequent visits and stages of follow-up in both groups (not significant). Also in relation to the first visit, a significant decrease in encopresis episodes was shown and a further slow but significant decrease at 52 weeks of follow-up in both groups. The manometric data obtained from the CTM group showed a low percentage of children with normal defecation dynamics, namely 28%, which (significantly) increased to 38% at the last manometry.\n Anorectal manometry combined with CT compared with CT alone did not result in higher success rates in chronically constipated children. Therefore, anorectal manometry has no additional demystifying or educational effect on clinical outcome in chronically constipated children. This observation together with the observation in the current and previous studies that no correlation was found between (achievement of) normal defecation dynamics and success and that no relation was observed between volume of urge or critical volume and success leaves no diagnostic or therapeutic role for anorectal manometry in chronic constipated children, except its use as a diagnostic test to exclude Hirschsprung's disease. A simple CT is successful in 30% of severely constipated children who are referred to a tertiary hospital, underscoring the importance of long-lasting and adequate laxative treatment.", "To determine whether mechanical bowel preparation influences the incidence of anastomotic dehiscence following colorectal surgery, 186 patients undergoing elective left colonic or rectal resection were randomized before surgery to bowel preparation (n = 89) or no bowel preparation (n = 97). Surgical technique was standardized and no patient had a defunctioning colostomy. Seventeen patients were excluded (seven with preparation, ten without). Indications for surgery in the remaining 169 patients were carcinoma (133 patients), diverticular disease (26), inflammatory bowel disease (six) and miscellaneous conditions (four). Operations performed were left colonic resection or reversal of Hartmann's procedure (26 with preparation, 28 without) and anterior resection (56 versus 59). The overall morbidity rate (18 per cent) was similar in the two groups. All seven clinical anastomotic leaks occurred after low anterior resection, in three of the 39 patients who had undergone bowel preparation and four of the 36 who had not (P > 0.9). Two deaths occurred, both of patients who had received bowel preparation, one being secondary to anastomotic leakage. Bowel preparation does not influence outcome after elective colorectal surgery.", "Bowel preparation prior to colonic surgery usually includes antibiotic therapy together with mechanical bowel preparation (MBP). Mechanical bowel preparation may cause discomfort to the patient, prolonged hospitalization, and water and electrolyte imbalance. It was assumed that with the improvement in surgical technique together with the use of more effective prophylactic antibiotics, it was possible that MBP would no longer be necessary.\n There is no statistical difference in the postoperative results of patients who undergo elective colon resection with MBP as compared with those who have no MBP. Design and\n The study includes all patients who had elective large bowel resection at Campus Golda between April 1, 1999, and March 31, 2002. Emergency operations were not included. The patients were randomly assigned to the 2 study groups (with or without MBP) according to identification numbers. All patients were treated with intravenous and oral antibiotics prior to surgery. The patients in the MBP group received Soffodex for bowel preparation.\n A total of 329 patients participated in the study, 165 without MBP and 164 with MBP. The 2 groups were similar in age, sex, and type of surgical procedure. Two hundred sixty-eight patients (81.5%) underwent surgery owing to colorectal cancer and 61 patients (18.5%) owing to benign disease. The hospitalization period was longer in the bowel-prepared group (mean +/- SD, 8.2 +/- 5.1 days) as compared with the nonprepared group (mean +/- SD, 8.0 +/- 2.7 days). However, this difference was not statistically significant. The time until the first bowel movement was similar between the 2 groups: a mean +/- SD of 4.2 +/- 1.3 days in the nonprepared group as compared with a mean +/- SD of 4.3 +/- 1.1 days in the prepared group (P = NS). Four patients (1.2%) died in the postoperative course owing to acute myocardial infarction and pulmonary embolism. Sixty-two patients (37.6%) of the non-MBP group suffered from postoperative complications as compared with 77 patients (46.9%) of the MBP group.\n Our results suggest that no advantage is gained by preoperative MBP in elective colorectal surgery.", "To assess with a single-blinded, multicenter, randomized trial, the postoperative results in patients undergoing sphincter-saving rectal resection for cancer without preoperative mechanical bowel preparation (MBP).\n The collective evidence from literature strongly suggests that MBP, before elective colonic surgery, is of no benefit in terms of postoperative morbidity. Very few data and no randomized study are available for rectal surgery and preliminary results conclude toward the safety of rectal resection without MBP.\n From October 2007 to January 2009, patients scheduled for elective rectal cancer sphincter-saving resection were randomized to receive preoperative MBP (ie, retrograde enema and oral laxatives) or not. Primary endpoint was the overall 30-day morbidity rate. Secondary endpoints included mortality rate, anastomotic leakage rate, major morbidity rate (Dindo III or more), degree of discomfort for the patient, and hospital stay.\n A total of 178 patients (103 men), including 89 in both groups (no-MBP and MBP groups), were included in the study. The overall and infectious morbidity rates were significantly higher in no-MBP versus MBP group, 44% versus 27%, P = 0.018, and 34% versus 16%, P = 0.005, respectively. Regarding both anastomotic leakage and major morbidity rates, there was no significant difference between no-MBP and MBP group: 19% versus 10% (P = 0.09) and 18% versus 11% (P = 0.69), respectively. Moderate or severe discomfort was reported by 40% of prepared patients. Mortality rate (1.1% vs 3.4%) and mean hospital stay (16 vs 14 days) did not differ significantly between both groups.\n This first randomized trial demonstrated that rectal cancer surgery without MBP was associated with higher risk of overall and infectious morbidity rates without any significant increase of anastomotic leakage rate. Thus, it suggests continuing to perform MBP before elective rectal resection for cancer.", "A recent meta-analysis has questioned the value of bowel preparation in patients undergoing colorectal resection. The aim of this clinical trial was to evaluate whether a single phosphate enema was as effective as oral polyethylene glycol (PEG) solution in preventing anastomotic leakage.\n Patients were randomized to receive either a single phosphate enema or 3 litres of oral PEG solution before surgery. Patients were followed for a minimum of 6 weeks to detect anastomotic leakage.\n There were 147 patients in each group and the groups were evenly matched for putative risk factors at baseline. Patients in the enema group had more anastomotic leaks requiring reoperation than those in the PEG group (4.1 versus 0 per cent, P = 0.013; relative risk 2.04 (95 per cent confidence interval (c.i.) 1.82 to 2.30)). The mortality rate was higher in the PEG group (2.7 versus 0.7 per cent, P = 0.176; odds ratio 1.62 (95 per cent c.i. 0.45 to 36.98)).\n Bowel preparation with a phosphate enema was associated with an increased risk of anastomotic leakage requiring reoperation compared with oral PEG. These results do not support the routine use of a phosphate enema in patients undergoing elective colorectal surgery.", "Mechanical bowel preparation (MBP) is performed routinely before colorectal surgery to reduce the risk of postoperative infectious complications. The aim of this randomized clinical trial was to compare the outcome of patients who underwent elective left-sided colorectal surgery with or without MBP.\n Patients scheduled for elective left-sided colorectal resection with primary anastomosis were randomized to preoperative MBP (3 litres of polyethylene glycol) (group 1) or surgery without MBP (group 2). Postoperative abdominal infectious complications and extra-abdominal morbidity were recorded prospectively.\n One hundred and fifty-three patients were included in the study, 78 in group 1 and 75 in group 2. Demographic, clinical and treatment characteristics did not differ significantly between the two groups. The overall rate of abdominal infectious complications (anastomotic leak, intra-abdominal abscess, peritonitis and wound infection) was 22 per cent in group 1 and 8 per cent in group 2 (P = 0.028). Anastomotic leak occurred in five patients (6 per cent) in group 1 and one (1 per cent) in group 2 (P = 0.210) [corrected] Extra-abdominal morbidity rates were 24 and 11 per cent respectively (P = 0.034). Hospital stay was longer for patients who had MBP (mean(s.d.) 14.9(13.1) versus 9.9(3.8) days; P = 0.024).\n Elective left-sided colorectal surgery without MBP is safe and is associated with reduced postoperative morbidity.", "Nasogastric (NG) decompression after colorectal surgery is practiced commonly. Our aim was to determine whether routine NG decompression benefitted patients undergoing this type of surgery. Five hundred thirty-five patients were randomized prospectively to either NG decompression or no decompression. Stratification was by type of operation and patient age. Excluded were patients who had emergency surgery with peritonitis, extensive fibrous adhesions, enterotomies, previous pelvic irradiation, intra-abdominal infection, pancreatitis, chronic obstruction. prolonged operating times, or difficult endotracheal intubation. Two hundred seventy-four patients received NG decompression (Salem sump, Argyle Co., Division of Sherwood Medical, St. Louis, MO) and two hundred sixty-one did not. There were 33 protocol violations included in the 535 patients. Patients who were not decompressed experienced significantly more abdominal distention, nausea, and vomiting than did those patients who were. Moreover, 13% required subsequent NG decompression as opposed to a reinsertion rate of 5% for patients routinely decompressed. The mean length of hospitalization for both groups was 11 days. There were no significant differences in nasopharyngeal or gastric bleeding, inability to cough effectively, respiratory infections, wound disruptions, reoperation, and wound infection rates (5%) between the two groups. We conclude that even though there is an increase in the rate of minor symptoms of nausea, vomiting, and abdominal distention, routine nasgastric decompression is not warranted after elective colon and rectal surgery.", "Pre-operative preparation of the colon is carried out with oral and/or intravenous administration of antibiotics and through the mechanical preparation of the colon using various substances to decrease the intraluminal bacterial concentration and remove the larger quantity of fecal material as possible, thus decreasing the risk of anastomosis dehiscence due to an increase in the intraluminal pressure. The role of antibiotics has been completely established while that of mechanical preparation is still questioned. The objective of this study is to assess the actual impact of mechanical preparation on colorectal surgery.\n Forty seven patients who underwent elective colorectal surgery were prospectively evaluated, out of which only 24 had mechanical preparation. We compared variables such as age, sex, preoperative hemoglobin, albumin and leukocyte values, surgery characteristics and type of anastomosis, as well as complications in both groups. Results: We found a higher incidence of fistulas, dehiscences and general complications in the group undergoing mechanical preparation of the colon.\n The results show that mechanical preparation of the colon does not provide any benefit and may result in a higher incidence of complications in colorectal surgery.", "Low anterior resection with coloanal anastomosis prevents a definitive stoma in patients with distal rectal cancer. However, imperative stool urge, stool fragmentation, prolonged stooling sessions, and minor problems of incontinence are frequently observed in the postoperative situation and negatively affect quality of life. Therefore, the colonic J-pouch was originally constructed to create a stool reservoir. In a randomized, prospective study, the short (5 cm) colonic J-pouch was tested for function and continence vs. straight coloanal anastomosis.\n Over a period of 30 months, 74 consecutive patients (55 males) with rectal cancer in the lower and middle third of the rectum were included and randomized into two groups. Anastomosis was performed either as a coloanal or a colon-pouch-anal anastomosis. The standardized surgical procedure included mobilization of the left hemicolon, central ligation of the inferior mesenteric artery and vein, preaortal lymph node dissection, autonomic nerve preservation, and total mesorectal excision. The anastomosis was performed at the upper anal canal or at the intersphincteric level. All patients were evaluated preoperatively and six months postoperatively for fecal continence, including sphincter manometry and defecation habits. In addition, quality of life was determined by use of a standardized questionnaire (European Organization for Research and Treatment of Cancer, EORTC-QLQ-C30).\n Thirty-seven patients were randomized into each group. In general, problems with continence for liquids or gas occurred less frequently in the colonic J-pouch group 6 months after surgery. The frequency of bowel movements was lower in the J-pouch group (2.5 per day) than in the coloanal group (4.7 per day). Importantly, in a manometric study at the same postoperative point, neorectal capacity was decreased to a similar degree in both groups compared with the preoperative rectal volume. Thus, the expected and postulated reservoir effect could not be achieved by forming a 5-cm colonic J-pouch.\n The colonic J-pouch was superior with regard to continence for gas and liquids compared with a straight coloanal anastomosis. Furthermore, stool frequency was significantly lower in the J-pouch group than in the coloanal reconstruction group. However, because neorectal capacity decreased equally in both groups, we speculate that the advantage of the colonic J-pouch is not in the creation of a larger neorectal reservoir but rather may be related to decreased motility." ]	Despite the inclusion of more studies with a total of 5805 participants, there is no statistically significant evidence that patients benefit from mechanical bowel preparation, nor the use of rectal enemas. In colonic surgery the bowel cleansing can be safely omitted and induces no lower complication rate. The few studies focused in rectal surgery suggested that mechanical bowel preparation could be used selectively, even though no significant effect was found. Further research on patients submitted for elective rectal surgery, below the peritoneal verge, in whom bowel continuity is restored, and studies with patients submitted to laparoscopic surgeries are still warranted.
CD004299	[ "15604157", "7041654", "15302637", "16490980", "3063043", "12637979", "2810183", "20526718", "12015689", "15843702", "2194417", "2658918", "6735625", "3528240", "6404238", "8961683", "3902413", "380736", "12067168" ]	[ "Randomised controlled trial of intravenous antibiotic treatment for cellulitis at home compared with hospital.", "A comparative study of two antibiotic regimens for the treatment of operative site infections.", "Comparison of short-course (5 days) and standard (10 days) treatment for uncomplicated cellulitis.", "Quality control in chronic wound management: the role of local povidone-iodine (Betadine) therapy.", "Failure of topically applied antibiotics, added to systemic prophylaxis, to reduce perineal wound infection in abdominoperineal excision of the rectum.", "Evaluation of granulocyte-colony stimulating factor (Filgrastim) in infected diabetic foot ulcers.", "Comparison of two prophylactic single-dose intravenous antibiotic regimes in the treatment of patients undergoing elective colorectal surgery in a district general hospital.", "Prospective randomized clinical trial assessing the efficacy of a short course of intravenously administered amoxicillin plus clavulanic acid followed by oral antibiotic in patients with uncomplicated acute diverticulitis.", "Once-daily intravenous cefazolin plus oral probenecid is equivalent to once-daily intravenous ceftriaxone plus oral placebo for the treatment of moderate-to-severe cellulitis in adults.", "Flucloxacillin alone or combined with benzylpenicillin to treat lower limb cellulitis: a randomised controlled trial.", "Antibiotics in elective colon surgery. A randomized trial of oral, systemic, and oral/systemic antibiotics for prophylaxis.", "Oral prophylaxis with neomycin and erythromycin in colorectal surgery. More proof for efficacy than failure.", "Systemic prophylaxis with gentamicin-metronidazole in appendicectomy and colorectal surgery: a prospective controlled clinical study.", "Systemic administration of antibiotics in the management of venous ulcers. A randomized clinical trial.", "Acute nonperforating appendicitis. Efficacy of brief antibiotic prophylaxis.", "The efficacy of a single dose antibiotic regimen in adults undergoing tonsillectomy.", "Topical ampicillin in addition to a systemic antibiotic prophylaxis in elective colorectal surgery. A prospective randomized study.", "A double-blind trial of a single intravenous dose of metronidazole as prophylaxis against wound infection following appendicectomy.", "Oral versus systemic antibiotic prophylaxis in elective colon surgery: a randomized study and meta-analysis send a message from the 1990s." ]	[ "To compare the efficacy, safety, and acceptability of treatment with intravenous antibiotics for cellulitis at home and in hospital.\n Prospective randomised controlled trial.\n Christchurch, New Zealand.\n 200 patients presenting or referred to the only emergency department in Christchurch who were thought to require intravenous antibiotic treatment for cellulitis and who did not have any contraindications to home care were randomly assigned to receive treatment either at home or in hospital.\n Days to no advancement of cellulitis was the primary outcome measure. Days on intravenous and oral antibiotics, days in hospital or in the home care programme, complications, degree of functioning and pain, and satisfaction with site of care were also recorded.\n The two treatment groups did not differ significantly for the primary outcome of days to no advancement of cellulitis, with a mean of 1.50 days (SD 0.11) for the group receiving treatment at home and 1.49 days (SD 0.10) for the group receiving treatment in hospital (mean difference 0.01 days, 95% confidence interval -0.3 to 0.28). None of the other outcome measures differed significantly except for patients' satisfaction, which was greater in patients treated at home.\n Treatment of cellulitis requiring intravenous antibiotics can be safely delivered at home. Patients prefer home treatment, but in this study only about one third of patients presenting at hospital for intravenous treatment of cellulitis were considered suitable for home treatment.", "This prospective study was designed to compare the relative efficacy of two antibiotic regimens for the treatment of operative site infections subsequent to pelvic operations. Patients with endomyoparametritis after delivery or pelvic cellulitis subsequent to hysterectomy were randomized to treatment with the combination of penicillin-gentamicin or the single agent cefoxitin. Seventeen of the 26 patients (65%) with endomyoparametritis who were treated with penicillin-gentamicin were cured by antibiotic therapy alone, in comparison to 15 of 23 (65%) patients treated with cefoxitin. Fifty-eight percent of the patients with pelvic cellulitis who were treated with penicillin-gentamicin responded favorably, in comparison to 50% of the patients treated with cefoxitin. None of these differences was statistically significant. In this study, neither antibiotic regimen provided satisfactory initial treatment for surgically induced soft tissue pelvic infection. Moreover, 11 of the 28 patients with treatment failures (40%) developed serious sequelae of their primary infection.", "Cellulitis is a condition routinely encountered in the primary care setting. No previous study has compared a short (5 days) vs standard (10 days) course of therapy of the same antibiotic in patients with uncomplicated cellulitis.\n We performed a randomized, double-blind, placebo-controlled trial to determine if 5 days of therapy has equal efficacy to 10 days of therapy for patients with cellulitis. Of 121 enrolled subjects evaluated after 5 days of therapy for cellulitis, 43 were randomized to receive 5 more days of levofloxacin therapy (10 days total antibiotic treatment), and 44 subjects to receive 5 more days of placebo therapy (5 days of total antibiotic treatment). Levofloxacin was given at a dose of 500 mg/d. Subjects were not randomized if they had worsening cellulitis, a persistent nidus of infection, a lack of any clinical improvement, or abscess formation within the first 5 days of therapy. The main outcome measure was resolution of cellulitis at 14 days, with absence of relapse by 28 days, after study enrollment.\n Eighty-seven subjects were randomized and analyzed by intention to treat. There was no significant difference in clinical outcome between the 2 courses of therapy (success in 42 [98%] of 43 subjects receiving 10 days of antibiotic, and 43 [98%] of 44 subjects receiving 5 days of antibiotic) at both 14 and 28 days of therapy.\n In patients with uncomplicated cellulitis, 5 days of therapy with levofloxacin appears to be as effective as 10 days of therapy.", "The treatment of venous leg ulcers is often inadequate, because of incorrect diagnosis, overuse of systemic antibiotics and inadequate use of compression therapy. Stasis dermatitis related to chronic venous insufficiency accompanied by infected superficial ulcers must be differentiated from erysipelas, cellulitis and contact eczema.\n To assess the effectiveness of (1) topical povidone-iodine with and (2) without compression bandages, (3) to compare the efficacy of systemic antibiotics and topical antimicrobial agents to prevent the progression of superficial skin ulcers.\n 63 patients presenting ulcerated stasis dermatitis due to deep venous refluxes were included in the study. The clinical stage of all patients was homogeneous determined by clinical, aetiological, anatomical and pathological classification. They were examined by taking a bacteriological swab from their ulcer area. Compression bandages were used in a total of 42 patients. Twenty-one patients with superficial infected (Staphylococcus aureus) ulcers were treated locally with povidone-iodine (Betadine), and 21 patients were treated with systemic antibiotics (amoxicillin). Twenty-one patients were treated locally with Betadine but did not use compression. The end point was the time of ulcus healing. The healing process of the ulcers was related to the impact of bacterial colonization and clinical signs of infection.\n Compression increases the ulcer healing rate compared with no compression. Using the same local povidone-iodine (Betadine) treatment with compression bandages is more effective (82%) for ulcus healing than without compression therapy (62%). The healing rate of ulcers treated with systemic antibiotics was not significantly better (85%) than that of the Betadine group. Using systemic antibiotics, the relapse rate of superficial bacterial infections (impetigo, folliculitis) was significantly higher (32%) than in patients with local disinfection (11%).\n Compression is essential in the mobilization of the interstitial lymphatic fluid from the region of stasis dermatitis. Topical disinfection and appropriate wound dressings are important to prevent wound infection. Systemic antibiotics are necessary only in systemic infections (fever, lymphangitis, lymphadenopathy, erysipelas).", "In a prospective, randomized trial, prophylactic use of topical antibiotics in addition to systemic prophylaxis was studied in patients undergoing abdominoperineal amputation of the rectum. All patients received gentamicin 80 mg and metronidazole 500 mg intravenously at induction of anesthesia, followed by the same dose 8 hourly for 48 hours. In accordance with the randomization, half of the patients were additionally given gentamicin 160 mg + metronidazole 400 mg topically into the perineal wound at closure. Perineal wound infection appeared in 19 of the 41 patients who received both systemic and topical prophylaxis, and in 18 of the 38 with only systemic antibiotics. Cell-mediated immunity was preoperatively assessed with a skin test (Multitest) in all but three patients. Impairment of cell-mediated immunity was associated with significantly heightened rate of wound infection, and these patients did not benefit from topical antibiotics.", "To re-evaluate the use of Granulocyte-Colony Stimulating Factor (G-CSF) in the treatment of infected diabetic foot ulcers.\n Thirty-seven diabetic subjects were randomised to Granulocyte-Colony Stimulating Factor (G-CSF) (n=20) or placebo (n=17). The primary endpoint was resolution of cellulitis, which was evaluated clinically and with an infection summary score. Patients were hospitalised for 10 days and received subcutaneously either 5 microg/kg G-CSF or placebo daily. Ulcers were treated with a standard wound protocol and the patients were instructed to stay in bed. All subjects received antibiotics (clindamycin and ciprofloxacin) intravenously until the inflammation had subsided.\n Patients who received G-CSF did not have an earlier resolution of clinically defined cellulitis (p=0.57). The infection summary score declined, but comparably, in both groups (G-CSF: 29.5+/-18.4 to 6.7+/-6.3 p<0.001, placebo: 24.2+/-16.9 to 8.9+/-7.2 p<0.001). The ulcer volume, which was not greater among placebo patients, was reduced by 59% in G-CSF and by 35% in placebo patients.\n We conclude that antibiotic and non weight-bearing therapy (bed rest) accelerated the resolution of cellulitis in infected foot ulcers. Additional treatment with G-CSF had no further beneficial effect.", "Two hundred and twenty-nine patients were entered into a study to compare the effectiveness and safety of two single-shot antibiotic regimes in patients undergoing elective colorectal surgery in two district general hospitals. A single shot of intravenous (IV) latamoxef disodium was as effective as an IV combination of cefuroxime and metronidazole in control of wound infection following elective large bowel surgery when given as a bolus at the time of anaesthetic induction. The incidence of major wound infection was 6% and was evenly distributed in the two treatment groups. Half the major wound infections were associated with faecal fistulae. A single shot of IV antibiotic at the time of anaesthetic induction was safe, simple and an effective prophylaxis against major wound infection. There was a low incidence (1.3%) of serious postoperative bleeding and no serious adverse reactions were noted. The overall mortality was 9%. Death was significantly related to elderly patients, a poor performance status, operative contamination and wound infections.", "Medical treatment of uncomplicated acute diverticulitis is not standardized, and there is an enormous diversity in clinical practice. Our aim was to demonstrate that uncomplicated diverticulitis can be managed with orally administered amoxicillin plus clavulanic acid and a short hospital admission.\n A prospective randomized trial was established to compare patients with uncomplicated diverticulitis who received oral antibiotic after a short course of intravenous antibiotic with those who received intravenous antibiotic for a longer period. The antibiotic treatment consisted of amoxicillin plus clavulanic acid 1 g every 8 h. We included 50 patients, 25 in each group. Patients in group 1 began oral antibiotic as soon as they improved and were discharged the day after. Patients in group 2 received intravenous antibiotic for 7 days. Both groups received oral antibiotic at discharge. The endpoint of the study was \"failure of treatment,\" which was defined as the impossibility of discharging on the expected day, emergency admission, or hospital readmission.\n Both groups were comparable in patient demographics and clinical characteristics. Most patients clearly improved between 24 and 48 h after admission. There were no significant differences between the groups when comparing failure of treatment. Treatment of patients in group 1 represented a savings in hospitalization costs of 1,244<euro> per patient.\n Most patients with uncomplicated diverticulitis can be managed safely with oral antibiotic; thus, a very short hospital stay is a safe option.", "A once-daily regimen of cefazolin (2 g intravenously [iv]) plus probenecid (1 g by mouth) was compared with a once-daily regimen of ceftriaxone (1 g iv) plus oral placebo in a randomized, double-blind equivalence trial of home-based therapy for moderate-to-severe cellulitis in adults. For the assessable recipients of cefazolin-probenecid (n=59) and ceftriaxone-placebo (n=57), clinical cure occurred at the end of treatment in 86% and 96% (P=.11), respectively, and was maintained at 1 month of follow-up in 96% and 91% (P=.55), respectively. The mean number of treatment doses (+/-standard deviation) given was similar in the 2 treatment arms (6.97+/-2.6 for cefazolin-probenecid and 6.12+/-2.1 for ceftriaxone-placebo; P=.06). The median antibiotic trough concentrations were 2.35 microgram/mL for cefazolin and 15.45 microgram/mL for ceftriaxone. Patients in the 2 treatment arms were similar with regard to overall rates of adverse reaction (P=.15), but nausea was more common among those in the cefazolin-probenecid arm (P=.048). The once-daily regimen of cefazolin-probenecid is a cheap, practical, and effective treatment option for moderate-to-severe cellulitis, and it avoids the need to use third-generation cephalosporins in most patients.", "To determine whether using intravenous benzylpenicillin in addition to intravenous flucloxacillin would result in a more rapid clinical response in patients with lower limb cellulitis.\n This was a randomised controlled trial set in an inner city teaching hospital, comprising 81 patients with lower limb cellulitis requiring intravenous antibiotics. The main outcome measure was the mean number of doses of antibiotic required until clinical response.\n The mean number of doses required was 8.47 (95% confidence interval (CI) 7.09 to 9.86) in the benzylpenicillin and flucloxacillin combined group. In the flucloxacillin only group it was 8.71 doses (95% CI 6.90 to 10.5), a mean difference of -0.24 doses (95% CI -2.48 to 2.01, p = 0.83). Other markers of treatment efficacy showed no difference between groups at review the following day; temperature decrease (mean difference -0.07 degrees C, 95% CI -0.76 to 0.62, p = 0.84), or diameter decrease of affected area (mean difference -34 mm, 95% CI -99 to 31, p = 0.30). Patient subjective assessments were also similar between the different drug regimen; improvement on a visual analogue scale of pain/discomfort from admission to first review (mean difference 10 mm, 95% CI -12.6 to 14.2, p = 0.91) and on second review (mean difference 15 mm, 95% CI -18.6 to 21.6, p = 0.88). Patient overall subjective feelings of improvement on first review (p = 0.32) and on second review (p = 0.64) were also similar.\n This study provides no evidence to support the addition of intravenous benzylpenicillin to intravenous flucloxacillin in the treatment of lower limb cellulitis.", "A prospective, randomized double-blind study was undertaken to compare the efficacy of three prophylactic regimens (oral neomycin and erythromycin, intravenous cefoxitin, and a combination of both oral and intravenous antibiotics) in patients undergoing elective colorectal surgery. One hundred sixty-nine patients were randomized and 146 patients were evaluable. Septic complications occurred in 11.4 per cent of patients receiving oral antibiotics only, in 11.7 per cent of patients receiving intravenous cefoxitin alone, and in 7.8 per cent of patients receiving both oral and intravenous antibiotics. These differences were not statistically different. The greatest number of septic complications occurred in those patients with anastomotic disruptions. Two patients died (1.3%), both of whom had major anastomotic failures. There was no advantage between any of the groups in the incidence of wound infection (3.9-6.8%). Thus, no advantage could be identified in this study in the combination of oral and intravenous antibiotics in elective colorectal surgery.", "In an open, prospective, and randomized investigation on the prophylactic efficacy of peroral neomycin sulfate-erythromycin base vs intravenous ceftriaxone-metronidazole preparation in colorectal surgery, no significantly diverging results between regimens were recorded (1/27 [3.7%] and 2/27 [7.4%] wound infections, respectively). Commentary is made about the diverging results from earlier studies on antimicrobial prophylaxis and on the multifactorial causality of surgical infection. We believe that variables such as physical condition of the patients, virulence and local resistance patterns of bacteria, and technical skill of the surgeons are far more important in regard to the postoperative outcome concerning septic complications than is the choice of proper antibiotics. Thus, to determine the efficacy of antimicrobial prophylaxis, we call for larger investigations in the future, preferably double-blind, where it is possible to better control and diminish the influence of determinants other than the antibiotics being compared.", "A prospective, randomized, clinical study was carried out in 188 patients undergoing appendicectomy or colorectal surgery to test the efficacy of prophylactic, parenterally-administered antibiotics in the prevention of infection. The results show the effectiveness of the association gentamicin-metronidazole (9.4% of infections), compared to the control group with no antibiotics (39.1% of infections), X2 = 14.1; P less than 0.001).", "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.", "A prospective, randomized, double-blind clinical study was performed to determine the efficacy of perioperative systemic antibiotics in preventing infection after appendectomy for acute nonperforating appendicitis. One hundred three patients received three doses of either placebo (saline, n = 52) or cefoxitin sodium (n = 51). The two groups were similar with regard to age distribution, sex ratio, duration of operation, pathologic condition of appendix, and hospital stay. Postoperative wound infections were detected in 9.6% of the placebo-treated patients, whereas none occurred in the cefoxitin group. All but one infection appeared after discharge. Cost analysis identified a net savings of $ 84 per patient with the use of prophylactic antibiotics. Septic morbidity after appendectomy for nonperforating appendicitis is significantly reduced by systemic antibiotics, and brief administration of a single broad-spectrum agent (cefoxitin) is effective prophylaxis.", "Several studies have indicated that antibiotics given for 5-7 days post-tonsillectomy are beneficial. A prospective double blind randomized study was undertaken to evaluate the efficacy of a long-acting antibiotic (Cefonicid) given prophylactically at the time of tonsillectomy. Dependent variables were percent weight loss, number of doses of pain medications required postoperatively, the number of days required to resume a normal diet, and return to work. The results of all independent tests indicated that there were no statistically significant differences between the Cefonicid group and the placebo group. The results of this study indicate that single dose prophylactic application of Cefonicid is not effective in adults undergoing tonsillectomy.", "Prophylactic use of topical ampicillin in addition to intravenous ampicillin and metronidazole was studied in a randomized trial including 203 consecutive patients undergoing elective colorectal surgery. All received ampicillin, 1 g X 3, and metronidazole, 0.5 g X 3, intravenously for at least three days from induction of anesthesia, and 105 also received topical ampicillin, 1 g, in each of the surgical wounds. Deep wound infection or dehiscence was seen in 12 of 105 having both administrations of antibiotics, and in nine of 98 having only intravenous antibiotics. The two groups were similar according to distribution of sex, age, type of surgery, and efficiency of bowel preparation. Topical ampicillin should be omitted in elective colorectal surgery when systemic prophylaxis with ampicillin and metronidazole is used.", "One hundred patients undergoing appendicectomy through a right iliac fossa incision were randomized to receive normal saline or 500 mg metronidazole as an intravenous infusion during the operation. One patient in the saline group developed an erythematous rash. There were 13 wound infections (as defined by the discharge of pus), 12 (out of 51) in the saline group and 1 (out of 49) in the metronidazole group. Bacteroides spp. were frequently cultured from the lumen of removed appendices and from pus obtained from infected wounds. This work supports the value of metronidazole but suggests that a single-dose regimen is adequate for prophylaxis.", "To compare the efficacy of combined oral and systemic antibiotics (combined) versus systemic antibiotics (systemic) alone in preventing surgical site infection in elective surgery of the colon, and to perform a meta-analysis of randomized studies comparing combined versus systemic antibiotics in elective colon surgery.\n A double-blind, placebo-controlled, randomized clinical trial.\n The Queen Elizabeth Hospital, Montreal, a university-affiliated community hospital.\n Two hundred and fifteen patients scheduled to undergo elective surgery of the colon.\n Patients were randomized to receive neomycin and metronidazole orally (109 patients) or identical placebos (106 patients) on the final preoperative day. All were given amikacin and metronidazole intravenously just before operation. Thirteen randomized series comparing combined and systemic antibiotic prophylaxis in elective colon surgery were identified for meta-analysis.\n Rates of postoperative surgical site infections: risk differences, risk ratios (RRs) and 95% confidence intervals (CIs); organisms found in the colon and wound fat at surgery, and in infected wounds.\n Three patients in the systemic group, and 5 in the combined group were excluded. Wound infections occurred in 5 patients in the combined group but in 17 in the systemic group (p < 0.01, RR = 0.29, 95% CI 0.11-0.75). Bacteria isolated from wound infections and wound fat were similar to those found in the colon. They were more frequent in the colon in the systemic group (p < 0.001) and occurred in wound fat in the systemic group twice as often as in the combined group (p < 0.001). By stepwise logistic regression, the presence of bacteria in wound fat at surgery was the strongest predictor of postoperative wound infection (p < 0.002). In the meta-analysis, the summary weighted risk difference in surgical site infections between groups (d(w)) and the summary RR both favoured combined prophylaxis (d(w) = 0.56, 95% CI 0.26-0.86; RR = 0.51, 95% CI 0.24-0.78; p < 0.001).\n In elective surgery of the colon combined oral and systemic antibiotics are superior to systemic antibiotics in preventing surgical site infections. Orally administered antibiotics add value by reducing bacterial loading of the colon and wound fat contamination, both associated with postoperative wound infection. Meta-analysis of randomized clinical trials reported from 1975 to 1995 supports these conclusions." ]	We cannot define the best treatment for cellulitis and most recommendations are made on single trials. There is a need for trials to evaluate the efficacy of oral antibiotics against intravenous antibiotics in the community setting as there are service implications for cost and comfort.
CD004825	[ "16020142", "16490019", "15834030", "16513872", "12547849", "12503977" ]	[ "Psychogenic erectile dysfunction: comparative study of three therapeutic approaches.", "Sexual counseling improved erectile rehabilitation after non-nerve-sparing radical retropubic prostatectomy or cystectomy--results of a randomized prospective study.", "A double blind, randomised study of sildenafil citrate for erectile dysfunction in men with multiple sclerosis.", "Sildenafil in the treatment of antipsychotic-induced erectile dysfunction: a randomized, double-blind, placebo-controlled, flexible-dose, two-way crossover trial.", "Sildenafil citrate for treatment of erectile dysfunction in men with type 1 diabetes: results of a randomized controlled trial.", "Treatment of antidepressant-associated sexual dysfunction with sildenafil: a randomized controlled trial." ]	[ "We administered the International Index of Erectile Function (IIEF; Rosen et al., 1997) questionnaire to 30 patients with psychogenic erectile dysfunction (ED) at baseline, immediately after treatment, and 3 months after treatment. We randomized patients into three groups: group I, who had weekly sessions of time-limited theme-based group psychotherapy for 6 months and 50 mg sildenafil citrate orally on demand; group II, who had an intake of 50 mg sildenafil citrate orally on demand for 6 months only; and group III, who had weekly sessions of time-limited theme-based group psychotherapy for 6 months. We analyzed data (15-item IIEF) for each group at three times during the study and compared by the data using analysis of variance (ANOVA), followed by the Bonferroni multiple comparison test. We used Cochran's Q-test for analysis between baseline and posttreatment stages of patients with remission of symptoms (EF equal to or higher than 26 points). Group III had a mean score higher than group II, with the difference being statistically significant (immediately after treatment, p = 0.033; at 3 months after treatment, p = 0.049; p < 0.05). All three therapeutic alternatives resulted in an improvement of erectile function domain score. However, significant differences from baseline were observed in groups I (p = 0.0009) and III (p = 0.0002) but not in group II (p = 0.135). The psychotherapy groups, I and III, had significantly higher scores compared with group II, in which patients were exclusively treated with sildenafil citrate. These findings suggest that time-limited theme-based group psychotherapy is an effective treatment for psychogenic ED.", "The efficacy of prostaglandin E1 (PGE1)-intracavernous injection (ICI) therapy for erectile dysfunction (ED) after non-nerve-sparing (NNS) radical pelvic surgery depends on patient compliance. The purpose of this study was to verify the utility of sexual counseling in ICI in terms of treatment efficacy, compliance, and dropout rate.\n In this prospective randomized study, 57 patients with ED after NNS radical prostatectomy or cystectomy were divided: 29 patients (group SC+) were treated with sexual counseling and PGE1-ICI therapy; the others 28 (group SC-) were treated with only ICI. At the start of the study all patients were administered the International Index of Erectile Function (IIEF) questionnaire and ICI training test; follow-up (at 3, 6, 9, 12, 18 months) was achieved by home Sildenafil test and ambulatory IIEF test; sexual counseling was provided only to group SC+.\n The mean IIEF score at the end of study was 26.5 (SC+) vs. 24.3 (SC-) (P < 0.05); eight patients (SC+, 27.5%) became responders to home Sildenafil vs. five (SC-, 17.8%) (P < 0.05); no dropout cases occurred (SC+) vs. eight (SC-, 28.5%) (P < 0.05). Moreover, we recorded best IIEF scores in group SC+ in sexual satisfaction (P < 0.05), sexual desire (P < 0.05), orgasmic function, and general satisfaction. Mean PGE1 doses were better in group SC+ (P < 0.05). ICI-oriented sexual counseling was utilized to motivate couples, to improve sexual intercourses, to correct mistakes in ICI administration. At the end of follow-up 21 patients (SC+) declared themselves satisfied vs. 12 (SC-).\n ICI-oriented sexual counseling in ICI increased the efficacy of treatment, the compliance, and Sildenafil responders rate, decreased the dropout rate.", "Identifying and effectively treating erectile dysfunction (ED) can result in an improvement of the quality of life (QoL) in men with multiple sclerosis (MS).\n This randomised, double blind (DB), placebo controlled, flexible dose study with an open label extension (OLE) assessed efficacy, QoL, and safety of sildenafil citrate in men with MS and ED. Overall, 217 men received sildenafil (25-100 mg; n = 104) or placebo (n = 113) for 12 weeks. Efficacy was assessed by the International Index of Erectile Function (IIEF) questionnaire that includes questions on achieving (Q3) and maintaining (Q4) an erection as well as a global efficacy question (GEQ). QoL was also assessed.\n After 12 weeks, patients receiving sildenafil had higher mean scores for IIEF Q3 and Q4 compared with those receiving placebo (p<0.0001), and 89% (92/103) reported improved erections compared with 24% (27/112) of patients receiving placebo (p<0.0001). At the end of the OLE phase, 95% of men reported improved erections. Patients receiving placebo during the DB phase showed a nearly fourfold increase in improved erections (97% v 26%). Men receiving sildenafil also showed improvements in five of the eight general QoL questions compared with men receiving placebo (p<0.05). The total mean score for the QoL questionnaire improved by 43% for the sildenafil group versus 13% for the placebo group (p<0.0001). Treatment related AEs were predominantly mild in nature, and no patient discontinued due to an AE.\n Sildenafil treatment for ED in men with MS was effective and well tolerated, and resulted in significant improvements in both general and disease specific QoL variables.", "Antipsychotic-induced erectile dysfunction is a significant clinical problem and is a common reason for poor medication compliance. This report studied the efficacy and tolerability of sildenafil citrate in patients with antipsychotic-induced erectile dysfunction.\n The study design was a randomized, double-blind, placebo-controlled, flexible-dose, two-way crossover trial carried out at a tertiary referral center. Thirty-two married male outpatients with schizophrenia or delusional disorder and antipsychotic-induced erectile dysfunction were recruited for the trial. Sexual function was assessed from patient logs of sexual activity.\n Thirty-two subjects and their spouses, who agreed to take part in the study, were included in the crossover trial. Thirty-one (96.9%) completed the trial. There was no significant period effect or treatment-period interaction. Patients reported significant improvement while taking sildenafil in the number of adequate erections, satisfaction with sexual intercourse, and the duration of erections over 2 weeks. The odds ratios for adequate erections and for satisfactory sexual intercourse with sildenafil were 4.07 and 3.77, respectively. The effect of sildenafil remained significant even after adjustment for period and week effects and treatment-period interaction with Poisson regression analysis. There were no major side effects or adverse drug interactions.\n Sildenafil citrate is safe and effective in the treatment of antipsychotic-induced erectile dysfunction. It is also well tolerated.", "In the 5-10% of diabetic men with type 1 diabetes, erectile dysfunction (ED) may be a particularly common and unwanted complication. This is the first study focusing exclusively on the effects of sildenafil in men with type 1 diabetes and ED.\n A total of 188 patients were entered into a double-blind, placebo-controlled, parallel-group, flexible-dose study and were randomized to receive sildenafil (25-100 mg; n = 95) or placebo (n = 93) for 12 weeks. Efficacy was evaluated using questions three (Q3; achieving an erection) and four (Q4; maintaining an erection) from the International Index of Erectile Function (IIEF), a global efficacy question (GEQ; \"Did treatment improve your erections?\"), and a patient event log of sexual activity.\n Improvements in mean scores from baseline to end-of-treatment for IIEF Q3 (35.7 vs. 19.9%) and Q4 (68.4 vs. 26.5%) were significant in patients receiving sildenafil compared with those receiving placebo (P = 0.0001). Moreover, the percent of improved erections (GEQ, 66.6 vs. 28.6%) and successful intercourse attempts (63 vs. 33%) was significantly increased with sildenafil compared with placebo. Improvements in sexual function were seen irrespective of the degree of ED severity. Adverse events were generally mild to moderate in severity, with headache (20 vs. 8%), flushing (18 vs. 3%), and dyspepsia (8 vs. 1%) reported more often in the sildenafil than in placebo-treated patients.\n Treatment with sildenafil for ED was effective, resulting in an increased percentage of successful attempts at intercourse, and was well tolerated among men with type 1 diabetes.", "Sexual dysfunction is a common adverse effect of antidepressants that frequently results in treatment noncompliance.\n To assess the efficacy of sildenafil citrate in men with sexual dysfunction associated with the use of selective and nonselective serotonin reuptake inhibitor (SRI) antidepressants.\n Prospective, parallel-group, randomized, double-blind, placebo-controlled trial conducted between November 1, 2000, and January 1, 2001, at 3 US university medical centers among 90 male outpatients (mean [SD] age, 45 [8] years) with major depression in remission and sexual dysfunction associated with SRI antidepressant treatment.\n Patients were randomly assigned to take sildenafil (n = 45) or placebo (n = 45) at a flexible dose starting at 50 mg and adjustable to 100 mg before sexual activity for 6 weeks.\n The primary outcome measure was score on the Clinical Global Impression-Sexual Function (CGI-SF); secondary measures were scores on the International Index of Erectile Function, Arizona Sexual Experience Scale, Massachusetts General Hospital-Sexual Functioning Questionnaire, and Hamilton Rating Scale for Depression (HAM-D).\n Among the 90 randomized patients, 93% (83/89) of patients treated per protocol took at least 1 dose of study drug and 85% (76/89) completed week 6 end-point assessments with last observation carried forward analyses. At a CGI-SF score of 2 or lower, 54.5% (24/44) of sildenafil compared with 4.4% (2/45) of placebo patients were much or very much improved (P<.001). Erectile function, arousal, ejaculation, orgasm, and overall satisfaction domain measures improved significantly in sildenafil compared with placebo patients. Mean depression scores remained consistent with remission (HAM-D score < or =10) in both groups for the study duration.\n In our study, sildenafil effectively improved erectile function and other aspects of sexual function in men with sexual dysfunction associated with the use of SRI antidepressants. These improvements may allow patients to maintain adherence with effective antidepressant treatment." ]	There was evidence that group psychotherapy may improve erectile function. Treatment response varied between patient subgroups, but focused sex-group therapy showed greater efficacy than control group (no treatment). In a meta-analysis that compared group therapy plus sildenafil citrate versus sildenafil, men randomised to receive group therapy plus sildenafil showed significant improvement of successful intercourse, and were less likely than those receiving only sildenafil to drop out. Group psychotherapy also significantly improved ED compared to sildenafil citrate alone. Regarding the effectiveness of psychosocial interventions for the treatment of ED compared to local injection, vacuum devices and other psychosocial techniques, no differences were found.
CD003281	[ "11226090", "10081532", "18043058", "12151925", "15385352", "11818760", "12067865", "16428565", "10764175", "2605083", "16492848", "18679598", "15872126", "2181138", "12477673", "8721471", "8447210", "9069860", "10513865", "11863320", "12705488", "15649161", "15321185", "9557910", "11300390", "12165828", "7892973", "7943830", "10840536", "11094579", "8488993", "9924226", "11093990", "14973803", "11080405", "10589605" ]	[ "The use of transcutaneous acupoint electrical stimulation for preventing nausea and vomiting after laparoscopic surgery.", "Effect and placebo effect of acupressure (P6) on nausea and vomiting after outpatient gynaecological surgery.", "Monitoring of neuromuscular blockade at the P6 acupuncture point reduces the incidence of postoperative nausea and vomiting.", "P6 acupoint injections are as effective as droperidol in controlling early postoperative nausea and vomiting in children.", "A randomized controlled comparison of electro-acupoint stimulation or ondansetron versus placebo for the prevention of postoperative nausea and vomiting.", "Electroacupuncture prophylaxis of postoperative nausea and vomiting following pediatric tonsillectomy with or without adenoidectomy.", "Acupressure and ondansetron for postoperative nausea and vomiting after laparoscopic cholecystectomy.", "Transcutaneous acupoint electrical stimulation with the ReliefBand for the prevention of nausea and vomiting during and after cesarean delivery under spinal anesthesia.", "Acupressure wristbands do not prevent postoperative nausea and vomiting after urological endoscopic surgery.", "Effect of stimulation of the P6 antiemetic point on postoperative nausea and vomiting.", "P6 acupressure does not prevent emesis during spinal anesthesia for cesarean delivery.", "Evaluation of transcutaneous electroacupoint stimulation with the train-of-four mode for preventing nausea and vomiting after laparoscopic cholecystectomy.", "Prevention of PONV by acustimulation with capsicum plaster is comparable to ondansetron after middle ear surgery.", "Postoperative nausea is relieved by acupressure.", "P6 acupressure may relieve nausea and vomiting after gynecological surgery: an effectiveness study in 410 women.", "Effect of P-6 acupressure on prevention of nausea and vomiting after epidural morphine for post-cesarean section pain relief.", "Comparison of P6 acupoint injection with 50% glucose in water and intravenous droperidol for prevention of vomiting after gynecological laparoscopy.", "Nonpharmacologic treatment of postoperative nausea.", "The effect of preoperative ondansetron on the incidence of postoperative nausea and vomiting in patients undergoing outpatient dentoalveolar surgery and general anesthesia.", "Efficacy of a single-dose ondansetron for preventing post-operative nausea and vomiting after laparoscopic cholecystectomy with sevoflurane and remifentanil infusion anaesthesia.", "Effect of acupressure on postoperative nausea and vomiting in laparoscopic cholecystectomy.", "Comparison of laser acupuncture and metoclopramide in PONV prevention in children.", "Acupressure for intrathecal narcotic-induced nausea and vomiting after caesarean section.", "Prevention of post-operative nausea and vomiting following laparoscopic surgery--ephedrine vs propofol.", "Neostigmine 50 microg kg(-1) with glycopyrrolate increases postoperative nausea in women after laparoscopic gynaecological surgery.", "Tropisetron vs ondansetron for prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy: a randomized double-blind, placebo-controlled study.", "P6 acupressure and nausea and vomiting after gynaecological surgery.", "Effects of ondansetron in the prevention of postoperative nausea and vomiting in children.", "[Tropisetron for prevention of nausea and vomiting in children undergoing tonsillectomy and/or adenoidectomy].", "Randomized, placebo-controlled trial of combination antiemetic prophylaxis for day-case gynaecological laparoscopic surgery.", "[Acupressure in the prevention of postoperative nausea and vomiting].", "Laser stimulation of acupuncture point P6 reduces postoperative vomiting in children undergoing strabismus surgery.", "Multimodal antiemetic management prevents early postoperative vomiting after outpatient laparoscopy.", "Acupressure wristbands for the prevention of postoperative nausea and vomiting in adults undergoing cardiac surgery.", "Antiemetic efficacy of prophylactic dimenhydrinate (Dramamine) vs ondansetron (Zofran): a randomized, prospective trial inpatients undergoing laparoscopic cholecystectomy.", "The safety and efficacy of prophylactic ondansetron in patients undergoing modified radical mastectomy." ]	[ "Nonpharmacologic techniques may be effective in preventing postoperative nausea and vomiting (PONV). This sham-controlled, double-blinded study was designed to examine the antiemetic efficacy of transcutaneous acupoint electrical stimulation (TAES) in a surgical population at high risk of developing PONV. We studied 221 outpatients undergoing laparoscopic cholecystectomy with a standardized general anesthetic technique in this randomized, multicenter trial. In the TAES group, an active ReliefBand(Woodside Biomedical, Inc., Carlsbad, CA) device was placed at the P6 acupoint, whereas in the Sham and Placebo groups, an inactive device was applied at the P6 acupoint and at the dorsal aspect of the wrist, respectively. The ReliefBand was applied after completion of electrocautery and remained in place for 9 h after surgery. The incidence of PONV and need for \"rescue\" medication were evaluated at predetermined time intervals. TAES was associated with a significantly decreased incidence of moderate-to-severe nausea as denoted on the Functional Living Index-Emesis score for up to 9 h after surgery (5%-11% for the TAES group vs 16%-38% [P < 0.05] and 15%-26% [P < 0.05] for Sham and Placebo groups, respectively). TAES was also associated with a larger proportion of patients free from moderate to severe nausea symptoms (73% vs 41% and 49% for Sham and Placebo groups, respectively; P < 0.05). However, there were no statistically significant differences among the three groups with regard to incidence of vomiting or the need for rescue antiemetic drugs. We conclude that TAES with the ReliefBand at the P6 acupoint reduces nausea, but not vomiting, after laparoscopic cholecystectomy.\n Transcutaneous acupoint electrical stimulation at the P6 acupoint reduced postoperative nausea, but not vomiting, in outpatients undergoing laparoscopic cholecystectomy procedures.", "Acupuncture and acupressure have previously been reported to possess antiemetic effect. We wanted to investigate the \"true\" and placebo effect of acupressure in prevention of postoperative nausea and vomiting (PONV).\n Sixty women undergoing outpatient minor gynaecological surgery were entered into a double-blind and randomised study. One group received acupressure with bilateral stimulation of P6 (A), a second group received bilateral placebo stimulation (P) and a third group received no acupressure wrist band and served as a reference group (R). PONV was evaluated as number of patients with complete response (no PONV), nausea only or vomiting. In addition, the need for rescue antiemetic medication and nausea after 24 h was registered.\n Complete response was obtained in 11, 11 and 9 patients in groups, A, P and R, respectively. Nine, 7 and 6 patients had nausea before discharge home, and 1, 1 and 8 patients were nauseated (8 vs 1 patient: P < 0.05) 24 h after operation in A, P and R groups, respectively. When compared to placebo acupressure (2 patients vomited and 5 needed rescue), significantly (P < 0.05) fewer needed rescue antiemetic medication after acupressure at P6 (no vomiting or rescue medication). When compared to the observation group (5 vomited and 4 needed rescue antiemetics), significantly fewer vomited after acupressure (P < 0.05)\n In patients undergoing brief gynaecological surgery, placebo effect of acupressure decreased nausea after 24 h but vomiting and need of rescue antiemetics was reduced only by acupressure with the correct P6 point stimulation.", "Electrical stimulation of the P6 acupuncture point reduces the incidence of postoperative nausea and vomiting (PONV). Neuromuscular blockade during general anesthesia can be monitored with electrical peripheral nerve stimulation at the wrist. The authors tested the effect of neuromuscular monitoring over the P6 acupuncture point on the reduction of PONV.\n In this prospective, double-blinded, randomized control trial, the authors investigated, with institutional review board approval and informed consent, 220 women undergoing elective laparoscopic surgery anesthetized with fentanyl, sevoflurane, and rocuronium. During anesthesia, neuromuscular blockade was monitored by a conventional nerve stimulator at a frequency of 1 Hz over the ulnar nerve (n = 110, control group) or over the median nerve (n = 110, P6 group) stimulating at the P6 acupuncture point at the same time. The authors evaluated the incidence of nausea and vomiting during the first 24 h.\n No differences in demographic and morphometric data were found between both groups. The 24-h incidence of PONV was 45% in the P6 acupuncture group versus 61% in the control group (P = 0.022). Nausea decreased from 56% in the control group to 40% in the P6 group (P = 0.022), but emesis decreased only from 28% to 23% (P = 0.439). Nausea decreased substantially during the first 6 h of the observation period (P = 0.009). Fewer subjects in the acupuncture group required ondansetron as rescue therapy (27% vs. 39%; P = 0.086).\n Intraoperative P6 acupuncture point stimulation with a conventional nerve stimulator during surgery significantly reduced the incidence of PONV over 24 h. The efficacy of P6 stimulation is similar to that of commonly used antiemetic drugs in the prevention of PONV.", "P6 acupuncture in adults is reported to be an effective preventive treatment for postoperative nausea and vomiting (PONV). It is not clear, however, whether this technique is effective as a preventive treatment for PONV in children.\n Children undergoing anesthesia and surgery were randomized to four groups: (a) intravenous saline + bilateral P6 acupoint injections (n = 50); (b) intravenous droperidol + bilateral P6 sham acupuncture (n = 49); (c) intravenous saline + bilateral sham point injections (n = 43); (d) intravenous saline +bilateral P6 sham acupuncture (n = 45). The perioperative anesthetic technique was standardized in all subjects. The incidence of postoperative nausea and vomiting (PONV) was evaluated in postanesthesia care unit (PACU) and 24 h after surgery.\n Incidence of nausea in the PACU was significantly lower in the acupoint group as compared with the sham point group (32% vs. 56%, P = 0.029) and P6 sham group (32% vs. 64%, P = 0.002) but not as compared with the droperidol group (32% vs. 46%, P = ns). Similarly, subjects in the acupoint group had a significantly lower incidence of vomiting in the PACU as compared with the sham point group (12% vs. 33%, P = 0.026) and P6 sham group (12% vs. 31%, P = 0.029) but not as compared with the droperidol group (12% vs. 18%, P = ns). The combined incidence of early PONV was also lower in the acupoint group as compared with the sham point group (P = 0.045) and P6 sham group (P = 0.004) but not as compared with the droperidol group (42% vs. 51%, P = ns). Finally, significantly fewer subjects in the acupoint group required intravenous ondansetron as an initial rescue therapy (P = 0.024). At 24 h after surgery, however, the incidence of late PONV was similar among the four study groups (P = ns).\n In children, P6 acupoint injections are as effective as droperidol in controlling early postoperative nausea and vomiting.", "In this study we evaluated the efficacy of electro-acupoint stimulation, ondansetron versus placebo for the prevention of postoperative nausea and vomiting (PONV). Patients undergoing major breast surgery under general anesthesia were randomized into active electro-acupoint stimulation (A), ondansetron 4 mg IV (O), or sham control (placement of electrodes without electro-acupoint stimulation; placebo [P]). The anesthetic regimen was standardized. The incidence of nausea, vomiting, rescue antiemetic use, pain, and patient satisfaction with management of PONV were assessed at 0, 30, 60, 90, 120 min, and at 24 h. The complete response (no nausea, vomiting, or use of rescue antiemetic) was significantly more frequent in the active treatment groups compared with placebo both at 2 h (A/O/P = 77%/64%/42%, respectively; P = 0.01) and 24 h postoperatively (A/O/P = 73%/52%/38%, respectively; P = 0.006). The need for rescue antiemetic was less in the treatment groups (A/O/P = 19%/28%/54%; P = 0.04). Specifically, the incidence and severity of nausea were significantly less in the A group compared with the other groups, and in the O group compared with the P group (A/O/P = 19%/40%/79%, respectively). The A group experienced less pain in the postanesthesia care unit, compared with the O and P groups. Patients in the treatment groups were more satisfied with their management of PONV compared with placebo. When used for the prevention of PONV, electro-acupoint stimulation or ondansetron was more effective than placebo with greater degree of patient satisfaction, but electro-acupoint stimulation seems to be more effective in controlling nausea, compared with ondansetron. Stimulation at P6 also has analgesic effects.", "Electrical stimulation of acupuncture point P6 reduces the incidence of postoperative nausea or vomiting (PONV) in adult patients. However, acupressure, laser stimulation of P6, and acupuncture during anesthesia have not been effective for reducing PONV in the pediatric population. The authors studied the effect of electrical P6 acupuncture in awake pediatric patients who had undergone surgery associated with a high incidence of PONV.\n Patients aged 4-18 yr undergoing tonsillectomy with or without adenoidectomy were randomly assigned to acupuncture, sham acupuncture, or control groups. Acupuncture needles at P6 and a neutral point were placed while patients were anesthetized, and low-frequency electrical stimulation was applied to these points for 20 min in the recovery room while the patients were awake (P6 Acu group). This treatment was compared with sham needles along the arm at acupuncture points not associated with antiemesis (sham group) and a no-needle control group. The arms were wrapped to prevent identification of treatment group, and anesthetic, analgesic, and surgical technique were standardized. Assessed outcomes were occurrence of nausea, occurrence and number of episodes of vomiting, time to vomiting, and use of antiemetic rescue medication.\n One hundred twenty patients were enrolled in the study, 40 per group. There were no differences in age, weight, sex, or opioid administration between groups. The PONV incidence was significantly lower with P6 acupuncture (25 of 40 or 63%; odds ratio, 0.135; number needed to treat, 3.3; P < 0.001) compared with controls (37 of 40 or 93%). Sham puncture had no effect on PONV (35 of 40 or 88%; P = not significant). Occurrence of nausea was significantly less in P6 Acu (24 of 40 or 60%; odds ratio, 0.121; P < 0.01), but not in the sham group (34 of 40 or 85%) compared with the control group (37 of 40 or 93%). Vomiting occurred in 25 of 40 or 63% in P6 Acu; 35 of 40 or 88% in the sham group, and 31 in 40 or 78% in the control group (P = not significant). Patients receiving sham puncture vomited significantly earlier (P < 0.02) and needed more rescue treatment (33 of 40 or 83%; odds ratio, 3.48; P < 0.02) compared with P6 Acu (23 of 40 or 58%) and the control group (24 of 40 or 60%).\n Perioperative P6 electroacupuncture in awake patients significantly reduced the occurrence of nausea compared with the sham and control groups, but it did not significantly reduce the incidence or number of episodes of emesis or the use of rescue antiemetics. Sham acupuncture may exacerbate the severity but not the incidence of emesis. The efficacy of P6 acupuncture for PONV prevention is similar to commonly used pharmacotherapies. Its appropriate role in prevention and treatment of PONV requires further study.", "To compare the efficacy of acupressure wrist bands and ondansetron for the prevention of postoperative nausea and vomiting (PONV).\n One hundred and fifty ASA I-II, patients undergoing elective laparoscopic cholecystectomy were included in a randomized, prospective, double-blind and placebo-controlled study. Patients were divided into three groups of 50. Group I was the control; Group II received ondansetron 4 mg iv just prior to induction of anesthesia; in Group III acupressure wristbands were applied at the P6 points. Acupressure wrist bands were placed inappropriately in Groups I and II. The acupressure wrist bands were applied 30 min prior to induction of anesthesia and removed six hours following surgery. Anesthesia was standardized. PONV were evaluated separately as none, mild, moderate or severe within six hours of patients' arrival in the postanesthesia care unit and then at 24 hr after surgery by a blinded observer. If patients vomited more than once, they were given 4 mg ondansetron iv as the rescue antiemetic. Results were analyzed by Z test. A P value of < 0.05 was taken as significant.\n The incidence of PONV and the requirement of rescue medication were significantly lower in both the acupressure and ondansetron groups during the first six hours.\n Acupressure at P6 causes a significant reduction in the incidence of PONV and the requirement for rescue medication in the first six hours following laparoscopic cholecystectomy, similar to that of ondansetron 4 mg iv.", "We randomized 94 patients undergoing cesarean delivery with spinal anesthesia to receive transcutaneous acupoint electrical stimulation using the ReliefBand at the P6 point (active group) or an active ReliefBand applied to the dorsum of the wrist (sham control group). The ReliefBand was applied 30-60 min preoperatively and left in place for 24 h. There was no statistically significant difference between the active and sham control groups in the incidence of intraoperative/postoperative nausea (30% versus 43%/23% versus 41%), vomiting (13% versus 9%/26 versus 37%), need for rescue antiemetics (23% versus 18%/34% versus 39%), or complete response (55% versus 57%/51% versus 34%). There was also no difference between the two groups in nausea scores, number of vomiting episodes, or patient satisfaction with postoperative nausea and vomiting management.", "To evaluate the efficacy of acupressure wristbands in the prevention of postoperative nausea and vomiting (PONV).\n Two hundred ASA I-II patients undergoing elective endoscopic urological procedures were included in a randomized, prospective, double blind, placebo-controlled study. Spherical beads of acupressure wristbands were placed at the P6 points in the anterior surface of both forearms in Group I patients (acupressure group, n = 100) whereas, in Group 2 (control group, n = 100) they were placed inappropriately on the posterior surface. The acupressure wristbands were applied 30 min before induction of anesthesia and were removed six hours postoperatively. Anesthesia was induced with thiopental and maintained with nitrous oxide and oxygen, fentanyl, isoflurane and vecuronium. The tracheas were extubated on the operation table after patients received neostigmine and atropine. Post operative nausea and vomiting were evaluated separately as none, mild, moderate or severe at the time of patient's arrival in PACU, then at six hours and twenty-four hours after surgery by a blinded observer.\n In the acupressure group, 25 patients had PONV compared with 29 patients in the control group (P = NS).\n Application of acupressure wristbands at the P6 of both forearms 30 min before induction of anesthesia did not decrease the incidence of PONV in patients undergoing endoscopic urological procedures.", "The antiemetic action of stimulation of the P6 (Neiguan) acupuncture (ACP) point has been studied in women, premedicated with nalbuphine 10 mg, undergoing minor gynaecological operations under methohexitone-nitrous oxide-oxygen anaesthesia. Invasive ACP--manual or electrical at 10 Hz--applied for 5 min at the time of administration of the premedication markedly reduced the incidence of vomiting and nausea in the first 6 h after operation, compared with untreated controls. This did not occur with stimulation of a \"dummy\" ACP point outside the recognized ACP meridians. Non-invasive methods (stimulation via a conducting stud or by pressure) were equally as effective as invasive ACP during the early postoperative period. However, both these non-invasive approaches were less effective than invasive ACP in the 1-6 h postoperative period, although each was as effective as two standard antiemetics (cyclizine 50 mg, metoclopramide 10 mg). In view of the total absence of any side effects in more than 500 ACP procedures, the clinical applications of this finding are worthy of further study.", "Nausea and vomiting are major adverse effects during spinal anesthesia for cesarean delivery. Stimulation of the P6 (Neiguan) acupoint is a traditional Chinese acupuncture technique used for effective antiemetic purposes. In this study, we evaluated the antiemetic effect of P6 acupressure in parturients during spinal anesthesia for cesarean delivery. In a randomized, double-blind, controlled trial, 110 parturients scheduled for elective cesarean delivery were enrolled in the study. Thirty minutes before initiation of spinal anesthesia, parturients were randomized to acupressure bands or placebo bands bilaterally on the P6 acupoint and nausea and vomiting were observed over the study period. There were no statistically significant differences in maternal characteristics. Incidence rates for intraoperative nausea were 64% (acupressure group) and 71% (control group) (P = 0.416), with an incidence of intraoperative vomiting of 22% (acupressure group) and 27% (control group) (P = 0.506). The results suggest that prophylactic use of acupressure bands bilaterally on the P6 acupoint failed to prevent nausea and vomiting during spinal anesthesia for cesarean delivery.", "To evaluate the efficacy of transcutaneous electroacupoint stimulation with a train-of-four (TOF) mode for the prevention of postoperative nausea and vomiting (PONV) in the patients undergoing laparoscopic cholecystectomy.\n Ninety-six ASA Grade I - II patients scheduled for laparoscopic cholecystectomy were randomized into Neiguan (P6) electroacupoint stimulation group (treated group) and a placebo control group (placement of electrodes without electroacupoint stimulation). The anesthetic regimen was standardized by needling at Neiguan on the left side and connecting the TOF peripheral nerve stimulator. The incidence of nausea, vomiting, severity, antiemetic dosage and the degree of pain were assessed at 0, 60, 120 min, and 24 h after surgery.\n The incidence of nausea and vomiting, the dose of antiemetics and the occurrence of severe nausea were all significantly lower in the treated group compared with the control group and the score for pain was obviously reduced in patients of the treated group at 24 h post-operation (P<0.05 or P<0.01).\n Transcutaneous electroacupoint stimulation at P6 with the TOF mode could reduce the incidence and severity of nausea and vomiting with analgesic effects.", "To compare the efficacy of stimulation of P6 acupoint with capsicum plaster in comparison with iv ondansetron for the prevention of postoperative nausea and vomiting (PONV).\n 120 patients of either sex, ASA I-II, undergoing elective middle ear surgeries under general anesthesia were included in this randomized, prospective, double-blinded and placebo-controlled study. The anesthetic technique was standardized. Patients were divided into three groups. Group I was the control group. Capsicum plaster (1 x 1 cm) was affixed at the P6 acupoint on both forearms 30 min before induction of anesthesia in patients of Group II. Patients of Groups I and III received an inactive adhesive plaster at the same site. Ondansetron 4 mg iv was given to patients of Group III at the end of surgery and the rest of the patients received a placebo. The plasters were removed six hours after transferring the patients to the postoperative unit. Criteria were fixed for the administration of rescue antiemetics (ondansetron 4 mg iv). PONV and the requirement for rescue antiemetics were recorded by a blinded observer.\n The incidence of PONV and the requirement for rescue antiemetics were significantly lower in both the acustimulation and ondansetron groups at six hours. At 24 hr there was a reduction in the requirement for rescue medication in the ondansetron group.\n Stimulation of the P6 acupoint with capsicum plaster is an effective method for prevention of PONV after middle ear surgery and its efficacy is comparable to ondansetron for the first six hours after surgery.", "One hundred and sixty-two general surgical patients were prospectively randomized to one of three treatments for postoperative nausea and vomiting: (1) acupressure using elasticated bands containing a plastic button to apply sustained pressure at the P6 (Neiguan) point above the wrist, (2) control dummy bands without the pressure button and (3) antiemetic injections of prochlorperazine with each opiate given and as required. All patients received papaveretum injections as required for pain, and additional prochlorperazine injections were prescribed if nausea was not controlled in groups 1 and 2. The severity of nausea was assessed using a linear analogue scale and was significantly (P = 0.002) reduced by acupressure on both days 1 and 2, in comparison to both controls and drug treated patients. The incidence of postoperative vomiting, and the need for unplanned antiemetic injections was also reduced by acupressure but this was not statistically significant. Acupressure can work and should be investigated in other clinical situations.", "To investigate the effect of sensory stimulation of the P6 point on postoperative nausea and vomiting (PONV) after gynecological surgery in the everyday clinical setting (effectiveness study).\n Four hundred and ten women undergoing general anesthesia for elective gynecological surgery were included in a prospective, consecutive, randomized, multicentre, placebo-controlled, double-blind clinical trial with a reference group. One group was given bilateral P6 acupressure (n = 135), a second group similar pressure on bilateral non-acupressure points (n = 139), and a third group (n = 136) served as reference group. Nausea (scale 0-6), vomiting, pain, and satisfaction with the treatment were recorded. Primary outcome was complete response, i.e., no nausea, vomiting or rescue medication for 24 hr. Results were analyzed by applying logistic regression with indicators of treatments, type of operation and risk score for PONV as explanatory variables.\n Complete response was more frequent in the P6 acupressure group than in the reference group (P = 0.0194) Conversely, the incidence of PONV was 46% in the reference group, 38% after pressure on a non-acupoint and 33% after P6 acupressure. The decrease from 46% to 33% was statistically significant. When considering vaginal cases separately, the decrease in PONV was from 36% to 20% (P = 0.0168). The corresponding decrease from 59% to 55% in the laparoscopic surgery group was not statistically significant.\n P6 acupressure is a non-invasive method that may have a place as prophylactic antiemetic therapy during gynecological surgery.", "Nausea and vomiting are important side effects following administration of epidural morphine for post-Cesarean section pain relief. Stimulation of the P-6 (Neiguan) acupoint is a traditional Chinese acupuncture modality used for antiemetic purpose; it has been found to be effective. The aim of this study was to evaluate the antiemetic effect of P-6 acupressure in parturients given epidural morphine for post-Cesarean section pain relief.\n In a randomized, double-blind and controlled trial, sixty parturients receiving epidural morphine for post-Cesarean section pain relief were investigated. Parturients were allocated to receive the acupressure bands or placebo bands on the P-6 acupoint bilaterally before the administration of spinal anesthesia and were observed over a 48-hour study period.\n The incidence of nausea and vomiting was significantly decreased from 43% and 27% in the control group, to 3% and 0% in the acupressure group, respectively (P < 0.05).\n The results demonstrate that prophylactic use of acupressure bands bilaterally on the P-6 acupoint can significantly reduce incidence of nausea and vomiting after epidural morphine for post-Cesarean section pain relief.", "Postoperative vomiting causes patients distress and delays discharge after outpatient surgery. Although P6 electroacupuncture is recognized as having an antiemetic effect, its inconvenient instrumentation may limit its clinical applicability. The purpose of this study was to explore a simple and effective alternative method for control of postoperative vomiting in outpatient surgery. We prospectively compared the effect of P6 acupoint injection with 0.2 ml 50% glucose in water (G/W) and intravenous injection of 20 micrograms/kg droperidol for prevention of vomiting in 120 consecutive outpatients undergoing gynecological laparoscopy with general anesthesia. Patients were randomly allocated to receive P6 acupoint injection, i.v. droperidol, or nothing as control group. Both P6 acupoint injection and i.v. droperidol 20 micrograms/kg were found to have a significant antiemetic effect when compared with the control group. We conclude that P6 acupoint injection with 50% G/W is a simple and effective method for reducing the incidence of postoperative emesis in outpatient surgery.", "Nausea is the most common postoperative complication of anesthesia. Appropriately applied acupressure offers a safe and cost-effective nursing approach to the prevention of this problem. This study tested the effect of acupressure on the incidence of postoperative nausea in same-day surgery patients.\n Ninety outpatient surgery patients were randomly assigned to one of three groups. The treatment group (n = 30) received bilateral elastic bands designed to exert pressure on the appropriate location on the distal aspect of the wrist during the perioperative period. The placebo group (n = 30) had elastic bands incapable of acupressure placed on their wrists. The control group (n = 30) received routine nursing and medical interventions for nausea and vomiting. Antiemetics were prescribed by the anesthesiologist and administered to patients in all three groups if nausea persisted and/or emesis occurred. The incidences of nausea or vomiting were tabulated separately for operating room, PACU phase I, and PACU phase II, and compared using Fisher's Exact Test.\n The incidence of nausea and vomiting did not differ overall in the OR or PACU phase I. However, in PACU phase II the incidence was 10% in the treatment group, 20% in the placebo group, and 50% in the control group (overall, P = .0001). Treatment wrist bands reduced the incidence of nausea and vomiting as compared with the control group (P = .0001), as did the placebo wrist bands (P = .0033). The numerical trend suggests that the incidence is reduced by half. The incidence of nausea can be significantly reduced by the use of placebo and suggests that further reduction can be obtained by using acupressure.", "The purpose of this investigation was to evaluate the efficacy of ondansetron in controlling postoperative nausea and vomiting (PONV) when used prophylactically in patients undergoing routine dentoalveolar surgery performed under general anesthesia.\n This was a prospective, double-blind, randomized, placebo-controlled evaluation. Fifty adult ASA I or II patients, requiring routine dentoalveolar surgery performed under general anesthesia, without a prior history of PONV, were randomly assigned to the experimental or control groups. Ondansetron (2.0 mL = 4.0 mg) or normal saline (2.0 mL) were administered intravenously before surgery. Age, gender, type of surgery, duration of surgery, anesthetic dosages, and PONV were evaluated. PONV was evaluated at time 0 (end of anesthesia) and at 30 and 60 minutes postoperatively. Nausea was evaluated using a visual analog scale (1, not nauseous; 5, about to vomit). Vomiting was assessed as a yes or no response. At 20 to 28 hours postoperatively, PONV was evaluated via a telephone call as a yes or no response, along with the number of episodes of nausea, vomiting, or both. Means and standard deviations were calculated for age, surgery, and anesthetics, and differences were assessed using an independent samples t-test. Differences for gender between the control and experimental groups were tested by a nonparametric chi-squared test. Differences between groups for nausea and vomiting were tested with a continuity correction chi-squared test. Differences were considered significant for a P < .05.\n No significant differences (P < .05) were found between the PONV groups for gender, duration of procedure, or anesthetic dosages. Statistically significant differences were noted in age and the type of surgical procedures performed. No statistically significant differences (P < .05) were noted between groups for nausea or vomiting.\n Based on the results of this study, PONV occurred in approximately 20% of patients (20% for nausea, 8% for vomiting). With the types of anesthetic agents and techniques used in this investigation, there were no significant differences between ondansetron and placebo for prophylaxis against PONV.", "In this randomized study we compared the efficacy of ondansetron 4 mg with ondansetron 8 mg for the prevention of postoperative nausea and vomiting (PONV) after laparoscopic cholecystectomy with sevoflurane and remifentanil infusion anaesthesia. Sixty patients were randomized to receive ondansetron 8 mg (30 pts) or ondansetron 4 mg (30 pts) before the induction of anaesthesia with thiopental and remifentanil. Anaesthesia was maintained with sevoflurane (0.5 MAC), oxygen and remifentanil infusion (0.25, 0.35, 0.5 microg/kg/min). Postoperative analgesia was provided by intravenous ketorolac 60 mg. The incidence of PONV, the pain score, and the analgesic requirement were recorded for 24 hours. There was no difference among groups in patient characteristics, risk factors for PONV, or side effects. During the first 6 h postoperatively, the incidence of PONV after ondansetron 4 mg and 8 mg were similar (p < 0.001). After 6 h the incidence of PONV increased significantly in patients who had received ondansetron 4 mg (p = 0.01) and was greater than that in patients who had received ondansetron 8 mg (p = 0.001). We conclude that single-dose ondansetron 8 mg is more effective than ondansetron 4 mg in the prevention of PONV after laparoscopic cholecystectomy. This surgery is associated with a high incidence of postoperative nausea and vomiting. A single dose of IV ondansetron 8 mg is well tolerated and decrease the number of nausea and vomiting episodes after surgery.", "To evaluate the effectiveness of acupressure applied at meridian P6 point for prevention of nausea and vomiting in patients undergoing laparoscopic cholecystectomy.\n A randomized double blind study was performed in 50 ASA I and II patients scheduled for laparoscopic cholecystectomy. Patients were divided into two groups; control and placebo. In the control group acupressure was applied at P6 point half an hour before surgery while in the placebo group the acupressure band was tied on meridian P6 point but the plastic bead was placed on the dosum of right forearm away from meridian P6 point. Patients were assessed for nausea and vomiting for six hours after surgery. Anaesthetic technique and postoperative analgesia were standardized for all patients.\n Results showed that the incidence of postoperative nausea and vomiting was 36% in the treatment group and 40% in placebo group, which is statistically insignificant.\n Application of acupressure at P6 point half an hour before induction of anaesthesia does not significantly alter the incidence of postoperative nausea and/or vomiting within 6 hours after surgery.", "Postoperative nausea and vomiting (PONV) are frequent side effects of general anesthesia in children. The aim of this study was to compare the effectiveness of laser acupuncture with metoclopramide in prevention of PONV in children after sevoflurane anesthesia.\n A total of 120 children ASA I and II, scheduled for hernia repair, circumcision or orchidopexy were randomly assigned into three groups: group I, received laser acupuncture on P6 point and saline infusion; group II, metoclopramide 0.1 mg.kg(-1) i.v. and sham laser; group III had sham laser and saline infusion. Anesthesia was maintained with sevoflurane and N(2)O/O(2). Patients were monitored for any symptoms of retching and vomiting at 2, 6 and 24 h postoperatively.\n The incidence of vomiting was higher in the control group in the first 2 h postoperatively (P < 0.001), compared with the other groups. There was no statistically significant difference between acupuncture and metoclopramide groups in occurrence and timing of vomiting (P < 0.001).\n Laser acupuncture is equally effective as metoclopramide in preventing PONV in children.", "In this randomized double-blind trial we investigated the effect of acupressure on the incidence of nausea and vomiting after caesarean section under spinal anaesthesia with added intrathecal morphine. Parturients wore either acupressure or placebo wristbands during surgery and postoperatively for at least 10 h. There was no significant difference overall between the two groups in the incidence of intra- or postoperative nausea or vomiting/retching. Demand for antiemetic medication was also similar in the two groups. However, in the sub-group of parturients who gave a previous history of postoperative nausea or vomiting, there was a statistically significant reduction in both postoperative nausea and vomiting/retching in the acupressure group. Further investigations are needed to see whether acupressure may be an effective non-pharmacological, non-invasive treatment for a common problem in this sub-group of patients.", "Postoperative nausea and vomiting (PONV) are relatively common troublesome distressing symptoms. The incidence is reported to be as high as 20-51%. Ninety adult ASA I and II patients scheduled for laparoscopic gynecological or surgical interventions, were randomly and equally assigned to one of the three groups in the immediate postoperative period: Group 1 received 0.1 ml.kg(-1) normal saline intravenously, while Group 2 received 0.5 mg.kg(-1) ephedrine intramuscularly and Group 3 received 0.25 mg.kg(-1) propofol intravenously as preventive antiemetic therapy. Sixty-six, 33 and 50 percent of patients experienced nausea and vomiting syndrome in Group 1, 2 and 3 respectively. Both ephedrine and propofol proved to have antiemetic properties. Ephedrine treated group of patient had significant less emetic score than propofol. No significant hemodynamic changes were recorded in both groups.", "Neostigmine, used for reversal of neuromuscular block, has been implicated in the development of postoperative nausea and vomiting (PONV). The use of mivacurium, which does not require neostigmine reversal due to its metabolism by plasma cholinesterase, has made it possible to study the effect of neostigmine on PONV in a randomised, double-blind, placebo-controlled manner.\n Ninety healthy women scheduled for laparoscopic gynaecological surgery were randomly allocated to two groups in a double-blind manner. One group was given neostigmine (50 microg kg(-1)) and glycopyrrolate (10 microg kg(-1)) (group NG), the other NaCl i.v. as placebo (group P) at the end of surgery when all the patients were spontaneously reversed to at least 75% of full muscle power. The risk of PONV was reduced by using low doses of opioids and ondansetron prophylaxis. All the patients were monitored and assessed for 24 h with regard to pain, nausea, vomiting and overall satisfaction.\n There was a statistically significant difference (P=0.03) in the occurrence of nausea during the first 6 h postoperatively between NG group (30%) and P group (11%), resulting in the more extensive use of antiemetic drugs in the NG group (28%) than in P group (7%) (P=0.01) in this period. There was no difference between the groups in the frequency of vomiting; seven nauseated patients had vomiting, four in group NG, three in group P. Total number of patients with PONV during the observation period of 24 h, usage of antiemetic rescue medication and overall patient satisfaction did not differ significantly between the groups.\n The results suggest that antagonism of neuromuscular block with a high dose of neostigmine increases postoperative nausea and the use of antiemetic drugs during the first 6 h after administration.", "Postoperative nausea and vomiting are observed in increased frequency after laparoscopic surgery. This study was performed in order to compare the efficacy of two 5-hydroxytryptamine-3 (5-HT3) receptor antagonists, ondansetron and tropisetron, in preventing postoperative nausea and vomiting (PONV) after laparoscopic cholecystectomy.\n Using a randomized, double-blind study design, 87 ASA I and II patients scheduled for laparoscopic cholecystectomy were randomly assigned to receive 4 mg ondansetron (Group A, n = 29), 5 mg tropisetron (Group B, n = 31), or placebo (Group C, n = 27) intravenously (IV) before induction of anesthesia. The end points evaluated were frequency of nausea, nausea intensity rated on a scale from 1 (mild) to 5 (most severe), frequency of vomiting, and need for rescue antiemetics. These parameters were measured immediately after surgery (0 h), at 3 h, 6 h, and 12 h postoperatively.\n The frequency of nausea was significantly higher in group A (31.2%) compared to group B (14%) at 12 h postoperatively (p <0.01). However, patients of group A had significantly lower nausea scores at 3 h postoperatively compared to group B. Postoperative vomiting occurred in 13.8% of patients in group A and 9.6% of patients in group B throughout the whole study period (p = n.s.). The need for rescue antiemetics was similar between groups A and B. Both groups were superior to placebo concerning all studied parameters.\n Our results show that ondansetron may be more effective in controlling nausea intensity during the first 3 h after laparoscopic cholecystectomy, while tropisetron has a longer-acting activity, with a major impact on nausea frequency at 12 h postoperatively.", "We studied the effect of P6 acupressure on 46 women undergoing laparotomy for major gynaecological surgery who received patient-controlled analgesia. Half the patients received acupressure at the P6 site, the remainder received acupressure at a \"sham\" site. There was a reduction in the requests for anti-emetic therapy in the group receiving P6 acupressure but there was no difference in the incidence of nausea and vomiting. There was no difference in total morphine consumption between the two groups.", "Postoperative nausea and vomiting (PONV) is a commonly observed adverse effect of general anesthesia. Recently, ondansetron, a new serotonin3 (5-hydroxytryptamine3) receptor antagonist was shown to be effective in the prophylaxis and prevention of chemotherapy-induced nausea and vomiting in children and adults as well as of PONV in adults. The aim of the current study was to evaluate the capacity of ondansetron to prevent PONV in pediatric patients.\n Two hundred children (132 boys and 68 girls) 2-10 yr of age received general inhalational anesthesia for surgical procedures (the extremities; ear, nose, and throat; inguinal hernia and phimosis; and dentistry) of an expected duration of less than 90 min. This study was divided into two phases: prophylaxis and rescue treatment. For prophylaxis, patients were randomly assigned to two groups: one group received an intravenous injection of 0.1 mg/kg ondansetron, and the other group received a placebo before surgical incision under double-blind conditions. For rescue treatment, only placebo patients were included; as a rescue medication they received an intravenous injection of 0.1 mg/kg ondansetron or 0.02 mg/kg droperidol according to a prestudy randomization under double-blind conditions. Incidence and severity of PONV (PONV score 0 = no nausea and no retching; 1 = complaining of sickness and retching; 2 = vomiting one or two time in 30 min; 3 = vomiting more than two times in 30 min) was recorded over a 4-h period in the postanesthesia care unit. Within 72 h of the procedure, a follow-up nurse interviewed the parents for late-onset nausea in the children.\n With regard to prophylaxis, 10% of patients receiving ondansetron had PONV during the 4-h observation period versus 40% of those receiving placebo (P < 0.001). The incidence of vomiting alone (PONV score > or = 2) was 5% and 25%, respectively (P < 0.001). There were no significant differences between ondansetron and droperidol in the treatment of PONV. However, at the end of the 4-h period, ondansetron patients were less sedated than were patients who had received droperidol (P < 0.01). Interviews with parents could be performed for 143 of 200 children (76 ondansetron and 67 placebo). Twenty-four children (15 ondansetron and 9 placebo) showed late-onset PONV after the 4-h observation period but within 24 h of the procedure (19.7% vs. 13.4%; P not significant).\n Ondansetron is effective in the prevention of PONV in pediatric patients for the first 4 h after general anesthesia. Lower sedation scores with ondansetron compared with droperidol may be an advantage, especially in ambulatory surgery. However, the incidence of late-onset PONV (> 4-24 h) was not influenced by prophylactic treatment with one dose of ondansetron preoperatively.", "Postoperative nausea and vomiting (PONV) after tonsillectomy is a common problem in children. Tropisetron is a new 5HT3 receptor antagonist and is successfully used in paediatric patients receiving cancer therapy. The aim of the study was to assess efficacy and safety of a single intravenous dose of tropisetron for prevention of PONV in paediatric patients at risk for postoperative vomiting.\n In a randomised, double-blind, placebo-controlled trial, we studied 98 children aged 2-12 years undergoing tonsillectomy or adenotonsillectomy. Patients received placebo or tropisetron 0.1 mg (= 0.1 ml)/kg body weight immediately after induction of anesthesia. A standard general anesthetic technique (Sevoflurane/N2O/O2 without neuromuscular blockers or opioids) was used. Perioperative vital signs, grade of sedation and episodes of postoperative nausea and vomiting were recorded.\n No vomiting episodes occurred in 65.3% of the tropisetron treated patients compared to 34.7% of the placebo group (p = 0.0024). Only 10.2% of the tropisetron treated patients vomited more than 3 times compared to 22.4% of the control patients (p = 0.0004). The need for antiemetic rescue medication was significantly lower in the study group (10.4%) compared to 28.6% (p = 0.025). No significant adverse effects of the study medication were shown.\n A single intravenous prophylactic dose of tropisetron effectively reduces the incidence of PONV during the first 24 postoperative hours after tonsillectomy and/or adenoidectomy. Because of the low incidence of adverse effects, the prophylactic use of tropisetron seems to be safe and justified in paediatric surgical patients at high risk for postoperative vomiting.", "In a randomized, double-blind trial, we compared i.v. ondansetron 4 mg (control), i.v. ondansetron 4 mg and cyclizine 50 mg (combination) and i.v. saline 0.9% (placebo), given after induction of standardized anaesthesia, for the prevention of nausea and vomiting (PONV) after day-case gynaecological laparoscopic surgery. Compared with placebo, fewer patients in the control group vomited (9/20 versus 11/59, P = 0.02) or needed rescue antiemetic (7/20 versus 9/59, P = 0.06) before discharge. Compared with the control, fewer patients in the combination group (n = 60) vomited (11/59 versus 2/60, P = 0.01) or needed rescue antiemetic (29/59 versus 2/60, P = 0.03) before discharge. The incidence of vomiting in the combination group was less than 5% overall. Compared with the control, the combination group had a significantly lower incidence (P = 0.001) and severity (P < 0.001) of nausea after discharge and more patients with no PONV at any time during the study (15/59 versus 27/60, P = 0.03). Unlike the placebo and control groups, no patient receiving combination prophylaxis was admitted overnight for PONV management.", "Despite modern anaesthetic procedures, postoperative nausea and vomiting are still the side-effects most often mentioned: acupressure is reported to be an additional method of preventing these effects in minor gynaecological surgery. We investigated the effectiveness of acupressure in patients undergoing gynaecological operations of longer duration (6-8 h) in a verum acupressure group compared to a placebo group. Before beginning the study we investigated a control group to find out the frequency of emesis. In the worst case of nausea that we encountered, 80% in the 0-6 h postoperative period, the number of random samples for the acupressure and placebo groups was calculated (30 patients in each group). The error for alpha was established at 5% and the reduction of nausea was 50%. METHODS. The female patients were 18 to 65 years old (ASA group I and II). Acupressure was carried out by fastening small metal bullets at the point P 6 to each forearm by means of an elastic bandage. The bullets were left there for 24 h. The premedication anaesthesia, postoperative analgesia, and antiemetic treatment were standardized. During a 24-h period we investigated the incidence of nausea and vomiting. RESULTS. The anthropometric data, the duration of surgery and the amount of postoperative analgesia were comparable between the three groups. Verum acupressure obtained a statistically significant and relevant reduction in nausea up to the 6th postoperative hour in comparison with the placebo group (P = 0.03). Nausea was reduced from 53% in the placebo group to 23% in the acupressure group. CONCLUSION. As demonstrated in this group of longer gynaecological surgery patients as well as in chemotherapy-induced nausea and vomiting, we were able to demonstrate that acupressure is an effective method of preventing nausea and vomiting without any side-effects. It is a valuable addition to the prevention of postoperative nausea and vomiting. Further studies should be conducted to investigate this possibility further.", "We conducted a double-blind, randomized, placebo-controlled study to investigate the effectiveness of P6 acupuncture on postoperative vomiting in children undergoing strabismus surgery. Acupuncture was performed by laser stimulation with a low-level laser. Laser stimulation of P6 was administered 15 min before induction of anaesthesia and 15 min after arriving in the recovery room. In the laser stimulation group, the incidence of vomiting was significantly lower (25%) than that in the placebo group (85%).", "Because no completely effective antiemetic exists for the prevention of postoperative nausea and vomiting (PONV), we hypothesize that a multimodal approach to management of PONV may reduce both vomiting and the need for rescue antiemetics in high-risk patients. After IRB approval, women undergoing outpatient laparoscopy were randomized to one of three groups. Group I (n = 60) was managed by using a predefined multimodal clinical care algorithm. Patients undergoing the same surgical procedure who received a standard balanced outpatient anesthetic with ondansetron 4 mg (Group II, n = 42) or placebo (Group III, n = 37) prophylaxis were chosen to establish baseline incidence of nausea and vomiting. None of the Group I patients vomited before discharge, compared with 7% in Group II (P = 0.07) and 22% in Group III (P = 0.0003). However, one patient (2%) in Group I required treatment for symptoms in the postanesthesia care unit, compared with 24% in Group II (P<0.0001) and 41% in Group III (P< 0.0001). Time to discharge-ready was significantly shorter in Group I (128, 118-139 min; mean, 95% confidence interval) versus Group II (162, 145-181 min; P = 0.0015) and Group III (192, 166-222 min; P = 0.0001). Patient satisfaction with control of PONV was not different between Group I and Group II. Return to normal daily activity and overall satisfaction were not different among groups. Multimodal management resulted in a 98% complete response rate and a 0% incidence of vomiting before discharge; however, this improvement did not result in an increased level of patient satisfaction when compared with routine monotherapy prophylaxis. We conclude that both multimodal management and routine monotherapy antiemetic prophylaxis resulted in an increased level of patient satisfaction than symptomatic treatment in this high-risk population.", "To determine whether the application of acupressure bands would lead to a reduction in postoperative nausea and vomiting after cardiac surgery.\n Prospective, randomized, double-blind clinical trial.\n University-affiliated tertiary care teaching hospital.\n Adult patients undergoing cardiac surgery.\n One hundred fifty-two patients were enrolled to receive either acupressure treatment (n = 75) or placebo (n = 77). All patients had acupressure bands placed on both wrists before induction of anesthesia; those in the treatment group had a bead placed in contact with the P6 point on the forearm.\n Patients were assessed for nausea, vomiting, and pain scores during the first 24 hours of the postoperative period. The incidences of nausea, vomiting, pain scores, and analgesic and antiemetic requirements were similar between the 2 groups. A subgroup analysis by gender implied that acupressure treatment may be effective only in female patients.\n Acupressure treatment did not lead to a reduction in nausea, vomiting, or antiemetic requirements in patients after cardiac surgery.", "The prophylactic administration of dimenhydrinate (Dramamine) is as effective as the use of ondansetron (Zofran) in preventing postoperative nausea and vomiting (PONV) in patients undergoing elective laparoscopic cholecystectomy. A prospective double-blind randomized study was performed in a tertiary care referral center.\n For this study, 128 American Society of Anesthesiology (ASA) physical statuses I, II, and III patients were randomly assigned to receive either ondansetron 4 mg intravenously (IV) at $17 per dose (group 1) or dimenhydrinate 50 mg IV at $2.50 per dose (group 2) before induction of anesthesia. The end points evaluated were frequency of PONV, need for rescue antiemetics, need for overnight hospitalization secondary to persistent nausea and vomiting, and frequency PONV 24 h after discharge.\n Chi-square tests and student's t-test were used to determine the significance of differences among groups. Of the 128 patients enrolled in this study, 20 were excluded: 15 patients received an additional antiemetic preoperative; 4 were converted to open cholecystectomies; and 1 procedure was aborted due to carcinomatosis. Of the 108 remaining participants, 50 received ondansetron (group 1) and 58 received dimenhydrinate (group 2). Both groups were well matched for demographics including gender, ASA class, and history of motion sickness. The need for rescue antiemetics occurred in 34% of group 1 and 29% of Group 2 (p = 0.376), postoperative vomiting in 6% of group 1 and 12% of group 2 (p = 0.228), and postoperative nausea in 42% of group 1 and 34% of group 2 (p = 0.422). One group 1 patient and two group 2 patients required overnight hospitalization for persistent nausea, a difference that was not significant. Rates of PONV 24 h after discharge were similar between groups 1 and 2 (10% vs 14%, p = 0.397 and 2% vs 5%, p = 0.375, respectively).\n Prophylactic administration of dimenhydrinate is as effective as the use of ondansetron in preventing PONV in patients undergoing elective laparoscopic cholecystectomy. Dimenhydrinate is the preferred drug because it is less expensive. With more than 500, 000 laparoscopic cholecystectomies performed in the United States each year, the potential drug cost savings from the prophylactic administration of dimenhydrinate instead of ondansetron exceed $7.25 million per year.", "We aimed to evaluate the antiemetic efficacy, safety, and clinical utility of prophylactic ondansetron administered at the end of the surgery for the prevention of postoperative nausea and vomiting (PONV) in a homogenous population of 54 women undergoing modified radical mastectomy (MRM). A standard general anesthetic and perioperative analgesic technique were used. After surgery, patients received either saline placebo or ondansetron 4 mg IV. Episodes of PONV, as well as rescue antiemetic requirements, were recorded for the first 24 h after surgery. The 24-h incidence of PONV (33.3% vs 81.5%; P = 0.0010) was significantly lower in the ondansetron group. The severity of PONV, evaluated by the number of emetic episodes per patient (1.59+/-1.90 vs 0.29+/-0.66; P = 0.0029), and the rescue antiemetic requirement (59.2% vs 14.8%; P = 0.0019) was significantly lower, in the ondansetron group. Patient satisfaction scores and number needed to prevent PONV (2.07) were significantly better and therapeutically more favorable in the ondansetron group. The incidence of adverse events such as headache, dizziness, and increased liver enzyme levels (number needed to harm = infinity) was similar in both groups. Administered at the end of the surgery in adult female patients undergoing general anesthesia for MRM, ondansetron 4 mg is effective and safe in preventing PONV. We recommend the clinical practice of routine prophylactic ondansetron to prevent PONV after MRM, as it significantly improves perioperative patient satisfaction and outcome.\n We evaluated the antiemetic efficacy, safety, and routine use of prophylactic ondansetron, a \"gold standard\" antiemetic, in women undergoing radical breast surgery who were at a high risk of postoperative vomiting. We analyzed more meaningful \"true\" and \"therapeutic\" outcome measures, and we conclude that prophylactic ondansetron is safe and effective and that its routine use is justified." ]	P6 acupoint stimulation prevented PONV. There was no reliable evidence for differences in risks of postoperative nausea or vomiting after P6 acupoint stimulation compared to antiemetic drugs.
CD002106	[ "1418507", "16679897", "2381003", "16881426", "20528992", "10748957", "3301861", "9625243", "9882058", "19892627", "20860635", "10626971", "16006842", "15315558", "2405749", "8150836", "3411648", "9848045", "19165109", "17901735", "17989948", "15993304", "9710723", "19562446", "11164668" ]	[ "DuoDERM hydroactive dressing versus silver sulphadiazine/Bactigras in the emergency treatment of partial skin thickness burns.", "Randomized clinical study of Hydrofiber dressing with silver or silver sulfadiazine in the management of partial-thickness burns.", "Comparison of a hydrocolloid dressing and silver sulfadiazine cream in the outpatient management of second-degree burns.", "Comparison of efficacy of 1% silver sulfadiazine and Acticoat for treatment of partial-thickness burn wounds.", "A prospective, randomized trial of silver containing hydrofiber dressing versus 1% silver sulfadiazine for the treatment of partial thickness burns.", "The role of alternative therapy in the management of partial thickness burns of the face--experience with the use of moist exposed burn ointment (MEBO) compared with silver sulphadiazine.", "Prospective clinical study of Hydron, a synthetic dressing, in delivery of an antimicrobial drug to second-degree burns.", "A prospective randomised clinical and histological study of superficial burn wound healing with honey and silver sulfadiazine.", "A silicone-coated nylon dressing reduces healing time in burned paediatric patients in comparison with standard sulfadiazine treatment: a prospective randomized trial.", "Xenoderm versus 1% silver sulfadiazine in partial-thickness burns.", "Clinical effectiveness of alginate silver dressing in outpatient management of partial-thickness burns.", "Biobrane versus 1% silver sulfadiazine in second-degree pediatric burns.", "A prospective, randomized trial of Acticoat versus silver sulfadiazine in the treatment of partial-thickness burns: which method is less painful?", "Treatment of partial-thickness burns: a prospective, randomized trial using Transcyte.", "Outpatient management of partial-thickness burns: Biobrane versus 1% silver sulfadiazine.", "Collagenase ointment and polymyxin B sulfate/bacitracin spray versus silver sulfadiazine cream in partial-thickness burns: a pilot study.", "Biosynthetic skin substitute vs. 1% silver sulfadiazine for treatment of inpatient partial-thickness thermal burns.", "A matched-pair, randomized study evaluating the efficacy and safety of Acticoat silver-coated dressing for the treatment of burn wounds.", "Randomized clinical study of SilvaSorb gel in comparison to Silvadene silver sulfadiazine cream in the management of partial-thickness burns.", "A liposome hydrogel with polyvinyl-pyrrolidone iodine in the local treatment of partial-thickness burn wounds.", "[Local therapy of grade IIa burns: efficacy and tolerability of a new hydrosome wound gel for the local treatment of grade IIa burns as compared with silver sulfadiazine ointment].", "Treatment of second degree facial burns with allografts--preliminary results.", "Prospective, randomized study of the efficacy of Mepitel on children with partial-thickness scalds.", "Aloe versus silver sulfadiazine creams for second-degree burns: a randomized controlled study.", "An open study comparing topical silver sulfadiazine and topical silver sulfadiazine-cerium nitrate in the treatment of moderate and severe burns." ]	[ "The study compared DuoDERM Burn Pack Hydroactive Dressings (DHD) with silver sulphadiazine/Bactigras dressings (SSD/Bactigras) in the outpatient management of small partial skin thickness burns. Forty-eight patients were entered into the study, and randomly allocated into either the DHD or SSD/Bactigras group. Burn wounds were followed until complete re-epithelialization occurred. There were no statistical differences between the groups, either with respect to their composition or characteristics of healing in days, and patients' subjective responses to treatment. However, application was easier in the DHD group (93 per cent), compared with 71 per cent in the SSD/Bactigras group (P = 0.0009), and the SSD/Bactigras were easier to remove (96 per cent) versus DHD (66 per cent, P = 0.0004). Furthermore, the DHD group had significantly less dressing changes; a mean of three changes per subject in the DHD group compared with eight in the SSD/Bactigras group (P = 0.117). Two burn wounds became infected in the DHD group, and one in the SSD/Bactigras group. In this study both modalities were found to be equally suitable and effective for small partial skin thickness burns.", "This prospective, randomized study compared protocols of care using either AQUACEL Ag Hydrofiber (ConvaTec, a Bristol-Myers Squibb company, Skillman, NJ) dressing with silver (n = 42) or silver sulfadiazine (n = 42) for up to 21 days in the management of partial-thickness burns covering 5% to 40% body surface area (BSA). AQUACEL Ag dressing was associated with less pain and anxiety during dressing changes, less burning and stinging during wear, fewer dressing changes, less nursing time, and fewer procedural medications. Silver sulfadiazine was associated with greater flexibility and ease of movement. Adverse events, including infection, were comparable between treatment groups. The AQUACEL Ag dressing protocol tended to have lower total treatment costs (Dollars 1040 vs. Dollars 1180) and a greater rate of re-epithelialization (73.8% vs 60.0%), resulting in cost-effectiveness per burn healed of Dollars 1,409.06 for AQUACEL Ag dressing and Dollars 1,967.95 for silver sulfadiazine. A protocol of care with AQUACEL(R) Ag provided clinical and economic benefits compared with silver sulfadiazine in patients with partial-thickness burns.", "The purpose of this prospective randomized study was to evaluate the use of an occlusive hydrocolloid dressing (Duoderm hydroactive, Squibb) and silver sulfadiazine (Silvadene, Marion) cream in the outpatient management of second-degree burns. The inclusion criteria consisted of burns less than 15% total body surface area that were evaluated within 24 hours of injury and did not require hospital admission. Fifty patients were randomly assigned after having been screened through a list of seven exclusion criteria. On initial evaluation the burns were photographed and screened for causative agent, location, size, depth, tetanus status, and presence of associated burns and injuries. Patients were seen in followup at least biweekly and evaluated for wound bed healing, wound margin healing, pain, number of dressing changes between visits, and ease of dressing application and removal. On final evaluation the burns were photographed and inspected for appearance of the healed burn, repigmentation, wound contraction, approximate time for dressing change, patient compliance, limitation of activity, overall impression of the treatment, and number of days for complete healing. Results were compared using a two-tailed t-test with p less than 0.01. Both groups were statistically similar in age, sex, and size. Duoderm-treated burns had statistically significantly better wound healing, repigmentation, less pain, fewer dressing changes, less time for dressing changes, and less cost. Duoderm-treated patients had statistically significantly less limitation of activity, better patient compliance, greater patient comfort, better overall acceptance, and felt the treatment was more aesthetically pleasing. The results reveal that the Duoderm Hydroactive dressings are superior to Silvadene cream in the outpatient management of second-degree burns.", "Acticoat (Smith & Nephew, Hull, UK) is a silver-coated dressing reported to reduce infection and exhibit antimicrobial activity in wounds.\n The purpose of the present study was to compare the efficacy ofacticoat and 1% silver sulfadiazine (1% AgSD) for treatment of partial thickness burn wounds.\n The authors reviewed 50 patients who had partial thickness burn wounds less than 25% admitted to Siriraj Burn Unit from May 2002 to September 2005. All patients were divided into 2 groups: the acticoat treated group (25 patients) and the 1% silver sulfadiazine treated group (25 patients). The 2 groups were compared for the etiology of burn wound, demographic data including age, sex, % Total Body Surface Area burn (TBSA%), cultured organisms, wound infection and outcome of Length Of hospital Stay (LOS) and level of pain.\n The authors found no significant differences in age, TBSA (%) between both groups. 7 patients (28%) developed wound infection. There were no differences in wound infection and LOS between both groups (p > 0.05). All of the patients who developed wound infection responded well to targeted topical and systemic antibiotic treatment. The 1% AgSD treated group (6 of 25, 24%) obtained more split thickness skin graft to close the granulation defects compared to patients who were treated with acticoat (4 of 25, 16%) but no statistical significance, p = 0.32). Average pain scores in the acticoat treated groups were significantly lower than the 1% AgSD treated group (4 +/- 0.6 versus 5 +/- 0.7, respectively).\n The present study confirms the efficacy of acticoat treatment in partial thickness burn wound. The authors conclude that acticoat has an advantage of limiting the frequency of replacement of the dressing and provides a less painful alternative to wound care with 1% AgSD with comparable incidence of burn wound infection. This is due to its long wear time and the ease of application and removal.", "Silver sulfadiazine has been used as a topical burn wound treatment for many years. Pain associated with dressing changes is a common problem in burn wounds. Aquacel Ag, a hydrofiber dressing coated with ionic silver has been reported to reduce burn wound infection and promote antimicrobial activity. The purpose of this study was to show the benefits of Aquacel Ag for the treatment of partial thickness burns. This prospective randomized study was conducted in 70 patients who had partial thickness burns less than 15% of total body surface area and were treated at Siriraj outpatient burn clinic during December 2006-February 2008. Patients were divided into two groups: Aquacel Ag-treated group with dressing changes every 3 days (35 patients) and 1% silver sulfadiazine-treated group, with daily dressing changes (35 patients). There was no difference in demographic data including age, gender, burn percentage between groups. Time-to-wound healing pain score during dressing change and cost of treatment were compared between both groups. Time-to-wound closure was significantly shorter in the Aquacel Ag-treated group (10 +/- 3 versus 13.7 +/- 4 days, P < 0.02) as well as pain scores at days 1, 3 and 7 (4.1 +/- 2.1, 2.1 +/- 1.8, 0.9 +/- 1.4 versus 6.1 +/- 2.3, 5.2 +/- 2.1, 3.3 +/- 1.9, respectively, P < 0.02). Total cost of treatment was 52 +/- 29 US dollars for the Aquacel Ag-treated group versus 93 +/- 36 US dollars for the silver sulfadiazine-treated group. This study showed that Aquacel Ag increased time to healing, decreased pain symptoms and increased patient convenience because of limiting the frequency of replacement of the dressing at lower total cost. This study confirms the efficacy of Aquacel Ag for the treatment of partial thickness burns at an outpatient clinic.", "Conventional management of partial thickness facial burn wounds includes the use of silver sulphadiazine dressings. Silver sulphadiazine forms an overlying slough that makes wound healing assessment difficult. Moist exposed burn ointment (MEBO) has been proposed as the ideal burn wound dressing both for burns of the face and other sites. Proponents of MEBO claim that it accelerates wound healing and results in scarless wound healing and at the same time reduce bacterial colonisation and the need for analgesics. We present here our experience with MEBO in the management of partial thickness burns of the face.\n One hundred and fifteen patients with partial thickness burns were randomly assigned to conventional treatment or MEBO. Out of this, 112 were analysed. Thirty-nine patients sustained facial burns; 17 received MEBO and 22 received silver sulphadiazine. Patients were followed up daily until the burn wounds were reduced by 75% of original body surface area (BSA).\n In patients with facial burns, MEBO was similar to silver sulphadiazine therapy with respect to rate of wound healing. Minimal slough was present over the wounds in MEBO-treated wounds resulting in clearer assessment of healing progression.\n Advantages of MEBO as compared to silver sulphadiazine in the management of partial thickness burns of the face include convenient change of dressing and easier assessment of healing progression. This suggests that MEBO is a useful alternative therapy for partial thickness burns of the face.", "This clinical trial prospectively evaluates the potential beneficial effects of antimicrobial drug delivery from a synthetic dressing (Hydron-AgSD) formed on second-degree burn wounds. A paste composed of polyethylene glycol-400, poly 2-OH ethylmethacrylate, and silver sulfadiazine (AgSD 1%-3%) matured within one hour to form a solid dressing. In 27 patients, comparable areas of second-degree wounds on the same patient were selected at random for test and control (silver sulfadiazine 1% only) sites. The mean total time of the synthetic dressing application per patient was about nine days, and each dressing remained in place for nearly four days. During this interval the control sites required four dressings changes. In 17 tests for infections, the control areas were contaminated but no bacteria were detected under the synthetic dressing; in three tests, the controls had no bacteria, whereas the synthetic dressing did. Healing of burns was similar under both types of dressing. Benefits of Hydron treatment included increased patient comfort because of the reduced number of dressing changes and, in some cases, greater freedom from contaminating bacteria.", "Histological and clinical studies of wound healing have been made on comparable fresh partial thickness burns with honey dressing or silver sulfadiazine (SSD) in two groups of 25 randomly allocated patients. Of the wounds treated with honey 84 per cent showed satisfactory epithelialization by the 7th day, and in 100 per cent of the patients by the 21st day. In wounds treated with silver sulfadiazine, epithelialization occurred by the 7th day in 72 per cent of the patients and in 84 per cent of patients by 21 days. Histological evidence of reparative activity was seen in 80 per cent of wounds treated with the honey dressing by the 7th day with minimal inflammation. Fifty two per cent of the silver sulfadiazine treated wounds showed reparative activity with inflammatory changes by the 7th day. Reparative activity reached 100 per cent by 21 days with the honey dressing and 84 per cent with SSD. Thus in honey dressed wounds, early subsidence of acute inflammatory changes, better control of infection and quicker wound healing was observed while in the SSD treated wounds sustained inflammatory reaction was noted even on epithelialization.", "Mepitel is a new grid like silicone coated nylon dressing containing no additional biological compounds. We describe a prospective randomized pilot study comparing Mepitel to the standard silver sulfadiazine cream (Flamazine) dressing for the topical treatment of paediatric burns. Seventy-six children presenting within 24 h of injury with a non previously treated burn were randomly assigned to Mepitel treatment (group M) or Flamazine treatment (group F). Age, sex, surface area of burn and causal agent were noted at admission. The depth of the burn, cumulative number of dressings, presence or absence of a complete epithelial cover, infection, bleeding and allergy were noted at each dressing change. There were 41 children in group M and 35 children in group F. Five children were subsequently withdrawn from each group because they required skin grafting. Analysis of the above mentioned criteria showed no statistical difference between the two groups except for the healing time (group M: 7.58+/-3.12, group F: 11.26+/-6.02, p < 0.01) and the number of dressings (group M: 3.64+/-1.5, group F: 5.13+/-2.9, p < 0.05). Mepitel has proved to be an easy-to-remove dressing, adhering only to intact skin. The faster healing time found in the Mepitel group may be related to a direct effect of silicone on epithelial growth or to a decrease in surface-cell damage compared to the silver sulfadiazine group. This attractive product will be further assessed on a larger scale trial to confirm our observations.", "The aim of this clinical trial was to evaluate the effectiveness of using lyophilised porcine skin (Xenoderm) compared with 1% silver sulfadiazine (SSD) in partial-thickness burns with regard to wound infection, length of hospital stay, number of dressings and doses of analgesics used (oral and injection).\n A total of 78 burns patients were included in this randomised study; their burns were caused by scalds or flames. They had second degree burns and had a burn area of 1060% of total body surface area (TBSA). Thirty-seven patients were treated with daily washing, followed by topical application of SSD dressing (the SSD group) and 39 with a biological dressing, i.e. Xenoderm (the Xenoderm group). The differences were evaluated using unpaired Student's t-test, Mann-Whitney U test and Chi-square test.\n There were no significant differences between the two groups with respect to age, gender, TBSA, cause of burn, and thickness of the burn or burn site. But there were significant differences regarding degree of wound infection, length of hospital stay, number of used dressings and given doses of analgesics.\n Xenoderm seems to be more effective than SSD dressing in terms of pain control, degree of wound infection, used wound dressings and length of hospital stay for partial-thickness burns. Prospective randomised studies are now necessary to compare possible reductions in the use of split thickness skin grafts and re-epithelialisation times.", "Askina Calgitrol Ag(®) (B. Braun Hospicare Ltd, Collooney Co. Sligo, Ireland), alginate silver wound dressing, is an advanced wound dressing which combines the potent broad-spectrum antimicrobial action of silver with enhanced exudate management properties of calcium alginate and polyurethane foam. The purpose of this study was to compare the efficacy of Askina Calgitrol Ag(®) and 1% silver sulfadiazine (1% AgSD) in the outpatient management of partial-thickness burn wounds at Burn Unit, Siriraj Hospital. A prospective descriptive study was conducted between January 2008 and January 2009 in Burn Unit, Division of Trauma Surgery, Siriraj Hospital, Mahidol University, Thailand. The 65 patients with partial-thickness burn wounds, less than 24 hours post-burn injury, had a total body surface area (TBSA%) less than 15% were treated at Siriraj Outpatient Burn Clinic. All patients were divided into Askina Calgitrol Ag(®) treated group (30 patients) and 1% AgSD treated group (35 patients). The data were compared by the demographics including age, gender, % TBSA burn, pain score, number of wound dressing change, nursing time and time of wound healing. Patients included in both groups were comparable with no significant differences in demographic data of age, gender, location of burn and type of burn injury (P > 0·05 evaluated by paired Student's t-test) between both group. The present results showed that average pain scores in the Askina Calgitrol Ag(®) treated group were significantly lower than the 1% AgSD treated group (2·23 ± 1·87 versus 6·08 ± 2·33, respectively) between both groups (P < 0·02). Patients treated with Askina Calgitrol Ag(®) had significantly lower number of wound dressing change (P < 0·02) and nursing time (P < 0·02) compared with 1% AgSD treated group. The Askina Calgitrol Ag(®) group needed less frequent wound dressing. Healing time was 7 ± 3·51 days after the application of Askina Calgitrol Ag(®). This was significantly shorter than that of control wounds (14 ± 4·18 days). Application of Askina Calgitrol Ag(®) leads to a good burn wound outcome. The present study confirms the effectiveness of Askina Calgitrol Ag(®) in the outpatient management of partial-thickness burn wounds.\n © 2010 The Authors. Journal Compilation © 2010 Blackwell Publishing Ltd and Medicalhelplines.com Inc.", "Partial-thickness burns in children have been treated for many years by daily, painful tubbing, washing, and cleansing of the burn wound, followed by topical application of antimicrobial creams. Pain and impaired wound healing are the main problems. We hypothesized that the treatment of second-degree burns with Biobrane is superior to topical treatment. Twenty pediatric patients were prospectively randomized in two groups to compare the efficacy of Biobrane versus 1% silver sulfadiazine. The rest of the routine clinical protocols were followed in both groups. Demographic data, wound healing time, length of hospital stay, pain assessments and pain medication requirements, and infection were analyzed and compared. Main outcome measures included pain, pain medication requirements, wound healing time, length of hospital stay, and infection. The application of Biobrane to partial-thickness burns proved to be superior to the topical treatment. Patients included in the biosynthetic temporary cover group presented with less pain and required less pain medication. Length of hospital stay and wound healing time were also significantly shorter in the Biobrane group. None of the patients in either group presented with wound infection or needed skin autografting. In conclusion, the treatment of partial-thickness burns with Biobrane is superior to topical therapy with 1% silver sulfadiazine. Pain, pain medication requirements, wound healing time, and length of hospital stay are significantly reduced.", "Despite recent improvements in analgesia, pain control during dressing changes continues to be a major challenge in patients with burns. We investigated two different dressing modalities to compare how much pain the patient experienced during and after the dressing change. Patients with partial-thickness burns that required only topical wound care were assigned randomly to treatment with Acticoat (Smith and Nephew USA, Largo, FL) or silver sulfadiazine (AgSD). The outcome variable was pain during wound care, which was measured using visual analog pain scores. The mean visual analog pain scores for the wounds treated with Acticoat or AgSD wounds were 3.2 and 7.9, respectively (P < .0001; paired Student's t-test). In 41 of the 47 paired pain score observations, the pain in the wound treated with AgSD was perceived as greater than in the wound treated with Acticoat. Burn wound care with Acticoat is less painful than burn wound care with AgSD in patients with selected partial-thickness burns.", "The purpose of the present study was to compare the effectiveness of three burns dressings (TransCyte, a bio-engineered skin substitute; Biobrane; and Silvazine cream (silver sulphadiazine and 0.2% chlorhexidine)), in treating children with partial-thickness burns. The primary objective was to determine the days until > or =90% re-epithelialization. The secondary objectives were to evaluate the number of wounds requiring autografting and the number of dressing changes/local wound care required.\n Study wounds were identified on each patient and the patients were randomized to receive TransCyte or Biobrane or Silvazine. Assessment of study wound closure began at 2 days after treatment and continued at least every other day thereafter until the wounds re-epithelialized or were autografted. A laser Doppler imaging system was used as an adjunct to assessing the depth of the burn.\n Thirty-three patients with 58 wound sites enrolled in the study (TransCyte, n = 20, Biobrane, n = 17; Silvazine, n = 21). Mean time to re-epithelialization was 7.5 days for TransCyte, 9.5 days for Biobrane, and 11.2 days for Silvazine. The number of wounds requiring autografting were 5/21 (24%) for Silvazine, 3/17 (17%) for Biobrane, and 1/20 (5%) for TransCyte.\n When used in partial-thickness burns in children, TransCyte promotes fastest re-epithelialization and required less overall dressings then Biobrane or Silvazine. Patients who received Silvazine or Biobrane require more autografting than those treated with TransCyte.", "A randomized, prospective study comparing the use of Biobrane (group 1) with the use of 1% silver sulfadiazine (group 2) in treating 56 partial-thickness burn wounds was carried out in 52 outpatients with burns that comprised less than 10% of their total body surface area. The two groups were similar in age, gender, race, and extent of burn. Wounds of patients in group 1 (30) were compared with those of group 2 (26) for healing time, pain, compliance with scheduled visits, and costs. Infected and skin-grafted wounds were excluded from healing time analysis. Infection rates of the two groups were similar (three of 30 vs two of 26). One patient in each group underwent skin grafting. Healing times of group 1 wounds were significantly less than those of group 2 (10.6 +/- 0.8 vs 15.0 +/- 1.2 days, P less than .01). Using a pain scale of 1 to 5, Biobrane-treated patients averaged lower pain scores at 24 hours after the burn (1.6 +/- 0.8 vs 3.6 +/- 1.3 P less than .001) and used less pain medication. Compliance with scheduled outpatient visits was also improved in the Biobrane-treated group (88.6% vs 63.2% attendance, P less than .001). Idealized total treatment costs averaged $434 for patients in group 1 compared with $504 for patients in group 2. We conclude that when used on properly selected wounds, Biobrane therapy can significantly decrease pain and total healing time without increasing the cost of outpatient burn care. Improved patient compliance may be an added benefit.", "A multifaceted approach that involves early debridement and control of infection is critical to successful and rapid burn wound healing. This pilot study was conducted in 15 adult patients with burns to assess the usefulness of early enzymatic debridement with a combination of collagenase ointment and polymyxin B sulfate/bacitracin spray versus silver sulfadiazine cream in partial-thickness burns. Combination treatment with collagenase and polymyxin B sulfate/bacitracin resulted in significantly shorter time to achieve a clean wound bed than silver sulfadiazine (median 6 vs 12 days; p = 0.0012) and significantly more rapid wound healing than silver sulfadiazine (median 10 vs 15 days; p = 0.0007). These results are encouraging and justify implementation of a larger, multicenter, comparative study.", "When used appropriately on superficial or moderate-depth partial-thickness burns, Biobrane significantly decreased total healing time to complete reepithelialization, reduced pain, and was associated with decreased nursing time and costs when compared to 1% silver sulfadiazine cream. Care must be used in selecting wounds for Biobrane therapy. They must be fresh, noninfected, and free of eschar and debris with a moist, sensate surface that demonstrates capillary blanching and refill. Wounds must be inspected regularly for nonadherence and signs of infection. Early fluid accumulation requires prompt aspiration. Biobrane should be removed if fluid reaccumulates or the Biobrane becomes nonadherent at any time after 48 hours. When used appropriately, Biobrane offers significant advantages over conventional therapy of acute partial-thickness burns.", "A new silver-coating technology was developed to prevent wound adhesion, limit nosocomial infection, control bacterial growth, and facilitate burn wound care through a silver-coated dressing material. For the purposes of this article, Acticoat (Westaim Biomedical Inc, Fort Saskatchawan, Alberta, Canada) silver-coated dressing was used. After in vitro and in vivo studies, a randomized, prospective clinical study was performed to assess the efficacy and ease of use of Acticoat dressing as compared with the efficacy and ease of our institution's standard burn wound care. Thirty burn patients with symmetric wounds were randomized to be treated with either 0.5% silver nitrate solution or Acticoat silver-coated dressing. The dressing was evaluated on the basis of overall patient comfort, ease of use for the wound care provider, and level of antimicrobial effectiveness. Wound pain was rated by the patient using a visual analog scale during dressing removal, application, and 2 hours after application. Ease of use was rated by the nurse providing wound care. Antimicrobial effectiveness was evaluated by quantitative burn wound biopsies performed before and at the end of treatment. Patients found dressing removal less painful with Acticoat than with silver nitrate, but they found the pain to be comparable during application and 2 hours after application. According to the nurses, there was no statistically significant difference in the ease of use. The frequency of burn wound sepsis (> 10(5) organisms per gram of tissue) was less in Acticoat-treated wounds than in those treated with silver nitrate (5 vs 16). Secondary bacteremias arising from infected burn wounds were also less frequent with Acticoat than with silver nitrate-treated wounds (1 vs 5). Acticoat dressing offers a new form of dressing for the burn wound, but it requires further investigation with greater numbers of patients in a larger number of centers and in different phases of burn wound care.", "This prospective, randomized study assessed the clinical, microbiological, and patient comfort characteristics of two silver-based topical agents in the management of partial-thickness burn wounds. Pediatric patients were randomly assigned to treatment with either SilvaSorb Gel (Medline Industries, Munedelein, IL) or Silvadene silver sulfadiazine cream (King Pharmaceuticals, Bristol, TN) for up to 21 days or to the point of full reepithelialization of the wound. Inclusion criteria were patients ranging in age from 2 months to 18 years with TBSA ranging from 1 up to 40%. A total of 24 patients were enrolled and completed the study. Findings demonstrated that the use of SilvaSorb Gel was associated with less pain and greater patient satisfaction when compared with Silvadene. No statistically significant differences were found when assessing the rate of infection, time to reepithelialization, or the number of dressings changes required during treatment. The reduction of pain and improved overall patient satisfaction with the use of SilvaSorb Gel compared with Silvadene indicates an important role for SilvaSorb Gel in treatment of partial-thickness burns in a pediatric population.", "Local treatment of burn injuries with conventional anti-infective preparations does not provide the moist environment that promotes fast wound healing. In a randomized controlled trial the effects of liposome polyvinyl-pyrrolidone-iodine (PVP-I) hydrogel, a novel formulation of PVP-I in a liposome hydrogel with high water-binding capacity, were investigated in 43 patients with partial-thickness burn wounds in an intraindividual comparison with a conventional silver-sulfadiazine cream. Treatment with liposome PVP-I hydrogel resulted in significantly faster complete healing of the burn wounds compared with silver-sulfadiazine cream (9.9 +/- 4.5 days versus 11.3 +/- 4.9; P < 0.015). The cosmetic result (smoothness, elasticity, appearance) was rated as excellent for 37.0% of study wounds with liposome PVP-I hydrogel compared with 13.0% of wounds treated with silver-sulfadiazine cream. Local tolerability was good; handling and change of dressing were rated as easy. Local treatment with liposome PVP-I hydrogel thus provides fast wound healing with a favorable cosmetic result.", "A new hydrosome wound gel is based on a new mechanism of action. It contains hydrosomes that penetrate to the wound bed and supply the wound with phospholipids, which are identical to membrane phospholipids of human cells. In this manner it supports the proliferative processes during wound healing.\n In a randomized, controlled, intraindividual comparative study of 47 patients with grade IIa burns, the hydrosome wound gel was tested against silver sulfadiazine cream. Digital pictures of the burn wounds were taken daily, and the wounds were analyzed in terms of their reepithelization rate.\n Wounds receiving the hydrosome wound gel healed 1.5-2 days faster than wounds treated with sulfadiazine cream (9.9+/-4.5 days vs. 11.3+/-4.9 days, p=0.015). In 66% of the patients, faster epithelization was observed with the hydrosome wound gel treatment. The hydrosome gel guaranteed secure prophylaxis against infection, and it was well tolerated and easy to apply.\n In this study, the treatment of grade IIa burn wounds with hydrosome wound gel led to faster wound closure compared with treatment with sulfadiazine cream. Therefore, hydrosome gel represents a good alternative to sulfadiazine cream.", "Facial burns are very common and have significant clinical impact. However, the treatment regimen for superficial to deep facial burns is not well defined. The purpose of this study was to investigate the effects of cadaver skin grafting in deep partial thickness facial burns in comparison to standard care. In a prospective open study design severely injured patients with superficial and deep partial thickness burns were randomized into the group receiving open treatment with silversulfadiazine (standard n=5) or into the group receiving early superficial debridement followed by coverage with glycerolized cadaver skin (n=5). The outcome measures were time and quality of wound healing, and incidence of hypertrophic scarring at 3 and 6 months post burn. There were no significant differences in demographics between groups. In the group treated with the allogenic material time to reepithelialization was 10.5 days, while it was 12.4 days in the silversulfadiazine group (p<0.05). Scar quality was found to be significantly improved in the allogenic treatment group. Three and 6 months postburn there were no patients with significant hypertrophic scarring in the allogenic group while there were two patients who developed hypertrophic scars in the silversulfadiazine group (p<0.05). In this study, we demonstrated that glyzerolized cadaver allograft skin represents a superior biological dressing for shallow and deep partial thickness facial burns. This is in concordance with other reports on scalds. It would be worthwhile to perform more clinical studies with a larger number of patients to further evaluate the effect and function of allogenic skin for facial burns.", "We performed a randomized clinical trial in which children with partial-thickness scald burns of less than 15% total body surface area were assigned treatment with either Mepitel (Mölnlycke Health Care) or silver sulfadiazine. Data were collected on time to wound healing, pain at dressing change, infection, and resource use. Student's t and chi-square tests were used to determine differences in the two groups. Healing times were compared using Kaplan-Meier survival curves. Wounds of children treated with Mepitel healed significantly faster than did controls' (p < 0.001), exhibited less eschar formation (p < 0.05), and experienced less pain at dressing change (p < 0.05). They also had significantly lower mean daily hospital charges ($1937 vs $2316; p = 0.025); as well as significantly lower charges for dressing changes and narcotics. There was no significant difference in wound infection. We believe the use of Mepitel represents a significant advance in the treatment of partial-thickness scald wounds in children.", "Burn injury is associated with a high incidence of death and disability; yet its management remains problematic and costly. We conducted this clinical study to evaluate the efficacy of aloe vera cream for partial thickness burn wounds and compare its results with those of silver sulfadiazine (SSD).\n Thirty patients with similar types of second-degree burns at two sites on different parts of the body were included in this study. Each patient had one burn treated with topical SSD and one treated with aloe cream, randomly.\n The rate of re-epithelialization and healing of the partial thickness burns was significantly faster in the site treated with aloe than in the site treated with SSD (15.9 +/- 2 vs 18.73 +/- 2.65 days, respectively; P < 0.0001). The sites treated with aloe were completely healed in less than 16 days vs 19 days for the sites treated with SSD.\n These results clearly demonstrated the greater efficacy of aloe cream over SSD cream for treating second-degree burns.", "Sixty patients with moderate and severe burns were randomly assigned to receive topical silver sulfadiazine (SSD) alone (n=30) or SSD combined with cerium nitrate (SSD-CN) (n=30). There were four deaths in the SSD group and one in the SSD-CN group; more patients with higher risk severity survived in the SSD-CN group. Wound infection did not differ significantly between the groups. The rate of re-epithelialization of partial thickness burns was faster by 8 days in the SSD-CN group. The relatively dry shell-like eschar of the SSD-CN-treated burn allowed planned excisions with immediate autologous grafting and the tissue beneath was ready to accept grafting 11 days earlier than in the SSD group (p=0.03). This resulted in a significantly shorter hospital stay for those in the SSD-CN group than in the SSD group (23.3 vs. 30.7 days; p=0.03) with consequent cost savings. A higher incidence of transient stinging pain was reported with application of SSD-CN, but this was effectively managed with analgesics where necessary. The results of this study confirm the greater efficacy of SSD-CN in the treatment of burns patients." ]	There is a paucity of high-quality evidence regarding the effect of different dressings on the healing of superficial and partial thickness burn injuries. The studies summarised in this review evaluated a variety of interventions, comparators and clinical endpoints and all were at risk of bias. It is impossible to draw firm and confident conclusions about the effectiveness of specific dressings, however silver sulphadiazine was consistently associated with poorer healing outcomes than biosynthetic, silicon-coated and silver dressings whilst hydrogel-treated burns had better healing outcomes than those treated with usual care.
CD006146	[ "8537695", "9754420", "9854758", "1573287", "2454440", "14996778", "11166969", "14622686", "10735802", "22151017", "10737286", "9932882", "12660386", "9554444", "8917240", "12370455", "9552068", "8622092", "12195763", "14499422", "11159256", "15157684", "6646208" ]	[ "Long-term intraspinal infusions of opioids in the treatment of neuropathic pain.", "[Intrathecal opioids in chronic non-malignant pain: relief and life quality].", "Opioid therapy for chronic noncancer back pain. A randomized prospective study.", "Long-term oral opioid therapy in patients with chronic nonmalignant pain.", "Lack of analgesic effect of opioids on neuropathic and idiopathic forms of pain.", "Effect of neurolytic celiac plexus block on pain relief, quality of life, and survival in patients with unresectable pancreatic cancer: a randomized controlled trial.", "The effect of opioids on phantom limb pain and cortical reorganization.", "Long-term management of noncancer pain with transdermal therapeutic system-fentanyl.", "Opioid substitution to improve the effectiveness of chronic noncancer pain control: a chart review.", "A Prospective, Randomized Trial of Intrathecal Injection vs. Epidural Infusion in the Selection of Patients for Continuous Intrathecal Opioid Therapy.", "Around-the-clock, controlled-release oxycodone therapy for osteoarthritis-related pain: placebo-controlled trial and long-term evaluation.", "A prospective study of long-term intrathecal morphine in the management of chronic nonmalignant pain.", "Oral opioid therapy for chronic peripheral and central neuropathic pain.", "Oral transmucosal fentanyl citrate: randomized, double-blinded, placebo-controlled trial for treatment of breakthrough pain in cancer patients.", "Patient-controlled analgesia for mucositis pain in children: a three-period crossover study comparing morphine and hydromorphone.", "Opioids versus antidepressants in postherpetic neuralgia: a randomized, placebo-controlled trial.", "Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial.", "A randomized, double-blind, double-dummy, crossover trial comparing the safety and efficacy of oral sustained-release hydromorphone with immediate-release hydromorphone in patients with cancer pain. Canadian Palliative Care Clinical Trials Group.", "Amitriptyline in neuropathic cancer pain in patients on morphine therapy: a randomized placebo-controlled, double-blind crossover study.", "Controlled-release oxycodone relieves neuropathic pain: a randomized controlled trial in painful diabetic neuropathy.", "The response of neuropathic pain and pain in complex regional pain syndrome I to carbamazepine and sustained-release morphine in patients pretreated with spinal cord stimulation: a double-blinded randomized study.", "Intrathecal opioid treatment for chronic non-malignant pain: a 3-year prospective study.", "Placebo and naloxone can alter post-surgical pain by separate mechanisms." ]	[ "Long-term intraspinal infusions of opioid drugs are being increasingly utilized in patients with noncancer pain. Despite this, there is a lack of long-term information, including success and failure rates for pain relief and technical problems. During a 5-year period, 18 noncancer patients underwent implantation of programmable infusion pumps for long-term intrathecal opioid infusion. Patients had (a) neuropathic pain, (b) had failed or been ineligible for noninvasive treatments, and (c) obtained greater than 50% pain relief with intrathecal trial infusions of morphine sulfate or sufentanil citrate. A disinterested third-party reviewer evaluated patients at the most recent follow-up. Sixty-one percent (11/18) of patients had good or fair pain relief with mean follow-up 2.4 +/- 0.3 years (0.8-4.7 years). Average numeric pain scores decreased by 39% +/- 4.3%. Five of the 11 responders required lower opioid doses (12-24 mg/day morphine) and the remaining six patients required higher opioid doses (> 34 mg/day morphine). Failure of long-term pain relief occurred in 39% (7/18) despite good pain relief in trial infusions and the use of both morphine and sufentanil. Technical problems developed in 6/18 patients but appeared to be preventable with further experience. Long-term intrathecal opioid infusions can be effective in treatment of neuropathic pain but might require higher infusion doses.", "The use of opioids for treatment of non-malignant pain is controversial. The evaluation of pain relief and of the quality of life of 11 severely incapacitated chronic non-cancer pain patients treated with long term intrathecal infusion of opioids trought implantable pumps was performed. The mean duration of pain complaints was 5.3 years. The mean pain intensity was 8.6. In 7 patients, pain episodes lasted at least 6 hours daily. The mean duration of the therapy was 19.6 months. After the treatment the mean pain score became 3.9. In only 1 patient, the duration of pain episodes was still longer than 6 hours. Quality of life improved in 36.36% of the cases. The long term spinal opioids through implantable pumps for non-malignant pains results in pain relief but not necessarily improves the quality of life.", "A randomized, open, long-term, repeated-dose comparison of an anti-inflammatory drug and two opioid regimens in 36 patients with back pain.\n To examine the long-term safety and efficacy of chronic opioid therapy in a randomized trial of patients with back pain.\n All participants underwent a 4-week washout period of no opioid medication before being randomly assigned to one of three treatment regimens for 16 weeks: 1) naproxen only, 2) set-dose oxycodone, or 3) titrated-dose oxycodone and sustained-release morphine sulfate. All patients then were assigned to a titrated dose of opioids for 16 weeks and then gradually tapered off their medication for 12 weeks. Finally, all participants were monitored for a 1-month posttreatment washout period. Each patient was called once a week for a report on pain, activity, mood, medication, hours awake, and adverse effects and was monitored carefully for signs of abuse and noncompliance.\n Weekly reports during the experimental phase showed the titrated-dose group to have less pain (P < 0.001) and less emotional distress (P < 0.001) than the other two groups. Both opioid groups were significantly different from the naproxen-only group. During the titration phase, patients also reported significantly less pain and improved mood. Few differences were found in activity or hours asleep, or between average pretreatment and posttreatment phone-interview and questionnaire variables. No adverse events occurred, and only one participant showed signs of abuse behavior.\n The results suggest that opioid therapy has a positive effect on pain and mood but little effect on activity and sleep. Opioid therapy for chronic back pain was used without significant risk of abuse. However, tapered-off opioid treatment is palliative and without long-term benefit.", "In contrast to the use of opioids for the treatment of acute and chronic cancer pain, the administration of chronic opioid therapy for pain not due to malignancy remains controversial. We describe 100 patients who were chronically given opioids for treatment of nonmalignant pain. Most patients experienced neuropathic pain or back pain. We used sustained-release dihydrocodeine, buprenorphine, and sustained-release morphine. Pain reduction was measured with visual analogue scales (VAS), and the Karnofsky Performance Status Scale was used to assess the patient's function. Good pain relief was obtained in 51 patients and partial pain relief was reported by 28 patients. Only 21 patients had no beneficial effect from opioid therapy. There was a close correlation between the sum and the peak VAS values (r = 0.983; p less than 0.0001) and pain reduction was associated with an increase in performance (p less than 0.0001). The most common side effects were constipation and nausea. There were no cases of respiratory depression or addiction to opioids. Our results indicate that opioids can be effective in chronic nonmalignant pain, with side effects that are comparable to those that complicate the treatment of cancer pain.", "The aim of the present study has been to assess the responsiveness of various types of chronic pain to opioids given i.v. and tested against placebo in a double-blind, randomized fashion. Pain classified as primary nociceptive was effectively alleviated (P greater than 0.001) while neuropathic deafferentation pain was not significantly influenced by morphine or equivalent doses of other opioids. Also 'idiopathic' pain, defined as chronic pain with no or little demonstrable pathology, failed to respond. The results were not related to whether the patients were regular users of narcotic analgesics or not. The outcome of our double-blind opioid test has proved useful to justify a continued, or discontinued, use of narcotic medication in individual patients. It may also support the indication and choice of invasive stimulation procedures (spinal cord or brain). The results of the study illustrate the misconception of chronic pain as an entity and highlight the importance of recognizing different neurobiological mechanisms and differences in responsiveness to analgesic drugs as well as to non-pharmacological modes of treatment. The opioid test has thus become a valuable tool in pain analysis and helpful as a guide for further treatment.", "Pancreatic cancer is an aggressive tumor associated with high mortality. Optimal pain control may improve quality of life (QOL) for these patients.\n To test the hypothesis that neurolytic celiac plexus block (NCPB) vs opioids alone improves pain relief, QOL, and survival in patients with unresectable pancreatic cancer.\n Double-blind, randomized clinical trial conducted at Mayo Clinic, Rochester, Minn. Enrolled (October 1997 and January 2001) were 100 eligible patients with unresectable pancreatic cancer experiencing pain. Patients were followed up for at least 1 year or until death.\n Patients were randomly assigned to receive either NCPB or systemic analgesic therapy alone with a sham injection. All patients could receive additional opioids managed by a clinician blinded to the treatment assignment.\n Pain intensity (0-10 numerical rating scale), QOL, opioid consumption and related adverse effects, and survival time were assessed weekly by a blinded observer.\n Mean (SD) baseline pain was 4.4 (1.7) for NCPB vs 4.1 (1.8) for opioids alone. The first week after randomization, pain intensity and QOL scores were improved (pain intensity, P< or =.01 for both groups; QOL, P<.001 for both groups), with a larger decrease in pain for the NCPB group (P =.005). From repeated measures analysis, pain was also lower for NCPB over time (P =.01). However, opioid consumption (P =.93), frequency of opioid adverse effects (all P>.10), and QOL (P =.46) were not significantly different between groups. In the first 6 weeks, fewer NCPB patients reported moderate or severe pain (pain intensity rating of > or =5/10) vs opioid-only patients (14% vs 40%, P =.005). At 1 year, 16% of NCPB patients and 6% of opioid-only patients were alive. However, survival did not differ significantly between groups (P =.26, proportional hazards regression).\n Although NCPB improves pain relief in patients with pancreatic cancer vs optimized systemic analgesic therapy alone, it does not affect QOL or survival.", "The efficacy of oral retarded morphine sulphate (MST) was tested against placebo in a double-blind crossover design in 12 patients with phantom limb pain after unilateral leg or arm amputation. Two counterbalanced treatment phases of 4 weeks each were initiated with an intravenous test infusion of MST or Placebo. The titration phase was 2 weeks. The dose of MST was titrated to at least 70 mg/day and at highest 300 mg/day. Pain intensity was assessed hourly on visual analog scales during a 4-week treatment-free phase, both treatment phases and at two follow-ups (6 and 12 months). Reorganization of somatosensory cortex, electric perception and pain thresholds as well as selective attention were measured pre- and post-treatment. A significant pain reduction was found during MST but not during placebo. A clinically relevant response to MST (pain reduction of more than 50%) was evident in 42%, a partial response (pain reduction of 25-50%) in 8% of the patients. Neuromagnetic source imaging of three patients showed initial evidence for reduced cortical reorganization under MST concurrent with the reduction in pain intensity. Perception and pain thresholds were not significantly altered whereas attention was significantly lower under MST. Thus, opioids show efficacy in the treatment of phantom limb pain and may potentially influence also cortical reorganization. These data need to be replicated in larger patient samples.", "Transdermal therapeutic system-fentanyl (TTS-F) has been extensively studied in cancer pain management. However, few studies have addressed the long-term management of noncancer pain, especially when it relates to neuropathic pain. A total of 529 patients were recruited into this prospective open-label study to determine the safety and effectiveness of TTS-F in relation to quality-of-life (QOL) stratified according to pain type and etiology. TTS-F significantly improves QOL within 28 days, and pain management within 48 hours. The frequency of side effects rapidly decreases over time, and patients not experiencing adequate pain management are identified within 28 days. The median duration of therapy for effective pain management was 10 months, and 90% of patients sustained such efficacy. TTS-F offers statistically significant increases in QOL-Short Form 12 (including the Physical Component Scale and Mental Component Scale measures) and pain control (Greek Brief Pain Inventory) from one time point to the next (P <.0001). These improvements are not influenced by pain type or etiology. TTS-F is a safe and effective pain management system independent of patient characteristics and demographic factors. What is of most importance is that in those patients with neuropathic pain, for whom opioids have long been thought to be ineffective, similar effectiveness is demonstrated when compared to patients with nociceptive pain.", "We evaluated the efficacy and tolerability of opioids in the long-term management of chronic noncancer pain. This retrospective chart review included 86 outpatients who started receiving, between 1994 and 1998, long-acting opioids. For each patient, the number of different opioids used and the efficacy and tolerability of each opioid prescribed were noted. During a mean follow-up of 8.8 +/- 6.3 mo, the number of opioids used by each patient was 2.3 +/- 1.4. Patient diagnoses were: back pain (31), neuropathy (20), joint pain (13), visceral pain (7), reflex sympathetic dystrophy (7), headache (5), fibromyalgia (3). The first opioid prescribed was effective for 36% of patients, was stopped because of side effects in 30%, and was stopped for ineffectiveness in 34%. Of the remaining patients, the second opioid prescribed after the failure of the first was effective in 31%, the third in 40%, the fourth in 56%, and the fifth in 14%. There was one case of addiction and no case of tolerance. We conclude that if it is necessary to change the opioid prescription because of intolerable side effects or ineffectiveness, the cumulative percentage of efficacy increases with each new opioid tested. Failure of one opioid cannot predict the patient's response to another. Implications: This study showed that if a patient receiving chronic opioid therapy experiences an intolerable side effect or if the drug is ineffective, changing to a different opioid may result in a lessening or elimination of the side effect and/or improved analgesia.", "The objective of this study was to compare the cost and safety of intrathecal injection (IN) vs. epidural infusion (CE) trial and to provide a preliminary assessment of the prognostic value of each in the selection of patients for long-term continuous intrathecal opioid therapy (CIOT). Thirty-seven patients with chronic nonmalignant pain who were being considered for CIOT were randomized to morphine trial by IN or CE. Analgesic response and complications were monitored throughout trial. Sixty-seven percent of IN (12/18) and 79% (15/19) of CE subjects reported good pain relief (defined as ≥ 50% pain reduction) and were implanted with a permanent infusion system. Eighty-nine percent (24/27) of subjects provided six-month CIOT follow-up data. Cost of trial and health care utilization during six months of CIOT were compared between groups. Analgesic and functional response during CIOT was also compared between IN and CE groups. The cost of IN trial was significantly less than CE trial (p < 0.001). Complications were generally mild in both groups, although opioid-related side effects tended to be more common in the IN group. Successful pain relief after six months of CIOT was reported by 10 (60%) and 14 (64%) patients who underwent IN and CE trial, respectively (p = 0.32; Fisher's exact test). There was no difference between IN and CE groups in McGill Pain rating, quality of life (VAS), mood (Profile of Mood States), or function (Sickness Impact Profile) after six months of CIOT. We conclude that intrathecal injection is a safe procedure for use in selection of patients for CIOT and is less costly than epidural infusion. Differences in pain and functional response to long-term opioids among patients selected by either trial method are not large.", "Although opioid analgesics have well-defined efficacy and safety in treatment of chronic cancer pain, further research is needed to define their role in treatment of chronic noncancer pain.\n To evaluate the effects of controlled-release oxycodone (OxyContin tablets) treatment on pain and function and its safety vs placebo and in long-term use in patients with moderate to severe osteoarthritis pain.\n One hundred thirty-three patients experiencing persistent osteoarthritis-related pain for at least 1 month were randomized to double-blind treatment with placebo (n = 45) or 10 mg (n = 44) or 20 mg (n = 44) of controlled-release oxycodone every 12 hours for 14 days. One hundred six patients enrolled in an open-label, 6-month extension trial; treatment for an additional 12 months was optional.\n Use of controlled-release oxycodone, 20 mg, was superior (P<.05) to placebo in reducing pain intensity and the interference of pain with mood, sleep, and enjoyment of life. During long-term treatment, the mean dose remained stable at approximately 40 mg/d after titration, and pain intensity was stable. Fifty-eight patients completed 6 months of treatment, 41 completed 12 months, and 15 completed 18 months. Common opioid side effects were reported, several of which decreased in duration as therapy continued.\n Around-the-clock controlled-release oxycodone therapy seemed to be effective and safe for patients with chronic, moderate to severe, osteo-arthritis-related pain. Effective analgesia was accompanied by a reduction in the interference of pain with mood, sleep, and enjoyment of life. Analgesia was maintained during long-term treatment, and the daily dose remained stable after titration. Typical opioid side effects were reported during short- and long-term therapy.", "To examine in a prospective manner the long-term safety and efficacy of chronic intrathecal morphine in patients with severe, nonmalignant pain refractory to less invasive modalities.\n Forty patients with severe, chronic nonmalignant pain poorly managed by systemic medications were identified as candidates for intraspinal trial of morphine. Thirty participants reported successful pain relief during trial and were implanted with an intraspinal delivery system. Standardized measures of pain and functional status were assessed before treatment was begun and at defined intervals during the subsequent 24 months. Intrathecal opioid use and pharmacological and device-related complications were also monitored.\n The participants had a mean age of 58 +/- 13 years and a mean pain duration of 8 +/- 9 years. Fifty-three percent of the study participants were women. Pain type was characterized as mixed neuropathic-nociceptive (15 of 30 patients, 50%), peripheral neuropathic (10 of 30 patients, 33%), deafferentation (4 of 30 patients, 13%), or nociceptive (1 of 30 patients, 3%). Forty-seven percent of the patients were diagnosed with failed back surgery syndrome. Significant improvement over baseline levels of visual analog scale pain was measured at each follow-up examination after implant. Overall, 50% (11 of 22 patients) of the population reported at least a 25% reduction in visual analog scale pain after 24 months of treatment. In addition, the McGill Pain Questionnaire, visual analog scale measures of functional improvement and pain coping, and several subscales of the Chronic Illness Problem Inventory showed improvement throughout the follow-up period. Pharmacological side effects were managed medically by morphine dose reduction, addition of bupivacaine, or replacement of morphine with hydromorphone. Device-related complications requiring repeat operations were experienced by 20% of the patients.\n Continuous intrathecal morphine can be a safe, effective therapy for the management of severe, nonmalignant pain among a carefully selected patient population and can result in long-term improvement in several areas of daily function.", "Although opioids are commonly used to treat chronic neuropathic pain, there are limited data to guide their use. Few controlled trials have been performed, and many types of neuropathic pain remain unstudied.\n Adults with neuropathic pain that was refractory to treatment were randomly assigned to receive either high-strength (0.75-mg) or low-strength (0.15-mg) capsules of the potent mu-opioid agonist levorphanol for eight weeks under double-blind conditions. Intake was titrated by the patient to a maximum of 21 capsules of either strength per day. Outcome measures included the intensity of pain as recorded in a diary, the degree of pain relief, quality of life, psychological and cognitive function, the number of capsules taken daily, and blood levorphanol levels.\n Among the 81 patients exposed to the study drug, high-strength levorphanol capsules reduced pain by 36 percent, as compared with a 21 percent reduction in pain in the low-strength group (P=0.02). On average, patients in the high-strength group took 11.9 capsules per day (8.9 mg per day) and patients in the low-strength group took close to the 21 allowed (18.3 capsules per day; 2.7 mg per day). Affective distress and interference with functioning were reduced, and sleep was improved, but there were no differences between the high-strength group and the low-strength group in terms of these variables. Noncompletion of the study was primarily due to side effects of the opioid. Patients with central pain after stroke were the least likely to report benefit.\n The reduction in the intensity of neuropathic pain was significantly greater during treatment with higher doses of opioids than with lower doses. Higher doses produced more side effects without significant additional benefit in terms of other outcome measures.\n Copyright 2003 Massachusetts Medical Society", "Patients with cancer frequently experience episodes of acute pain, i.e., breakthrough pain, superimposed on their chronic pain. Breakthrough pain is usually treated with short-acting oral opioids, most of which provide some relief after 15-20 minutes, with peak effects after 30-45 minutes. Oral transmucosal fentanyl citrate (OTFC), a unique formulation of the opioid fentanyl, has been shown to provide meaningful pain relief within 5 minutes in patients following surgery. We conducted a multicenter, randomized, double-blinded, placebo-controlled trial of OTFC for cancer-related breakthrough pain.\n Patients who were 18 years of age or older, receiving the equivalent of at least 60 mg oral morphine or at least 50 microg transdermal fentanyl per day for chronic cancer-related pain, and experiencing at least one episode of breakthrough pain per day were studied. After titration to an effective OTFC dose, subjects were given 10 randomly ordered treatment units (seven OTFC units and three placebo units) in the form of identical lozenges. If acceptable pain relief was not achieved within 30 minutes, subjects were instructed to take their previous breakthrough pain medication (i.e., rescue medication). Pain intensity, pain relief, and use of rescue medication were evaluated at 15-minute intervals over a 60-minute period.\n Eighty-nine of 92 patients who received the randomized treatment were assessable (i.e., treated with at least one unit of OTFC and one unit of placebo). OTFC produced significantly larger changes in pain intensity and better pain relief than placebo at all time points (two-sided P<.0001). Episodes treated with placebo required the use of rescue medication more often than episodes treated with OTFC (34% versus 15%; relative risk = 2.27; 95% confidence interval = 1.51-3.26; two-sided P<.0001).\n OTFC appears effective in the treatment of cancer-related breakthrough pain.", "(1) To test the safety and efficacy of a clinical protocol for administering opioid by using patient-controlled analgesia (PCA) for the management of mucositis pain in children after bone marrow transplantation, (2) to compare the efficacy, side-effect profile, and potency ratio of morphine with those of hydromorphone by using PCA as the method of opioid administration, and (3) to obtain pharmacokinetic data on hydromorphone and morphine in this population of children.\n In this double-blind, three-period crossover study, patients were randomly assigned to receive either morphine (group 1) or hydromorphone (group 2) initially by means of PCA on days 1, 2, and 3 (period 1), to be followed on days 4, 5, and 6 (period 2) with the alternative opioid, followed by the opioid used at the commencement of the study on days 7, 8, and 9 (period 3). A clinical protocol for calculating the PCA commencement opioid dose and subsequent opioid-dose escalation was tested by measures of safety and efficacy. Measures of pain intensity and opioid side effects were made during the three periods. On the last study day (day 10), patients received a continuous infusion of opioid derived from the previous 24-hour PCA opioid requirement, and blood specimens were collected and stored for subsequent opioid analysis.\n Ten patients were enrolled in this study. Rapid escalation in opioid requirement commonly occurred at the commencement of PCA, followed by a variable plateau phase and then deescalation of opioid requirement after mucositis resolution. The measures demonstrated the safety and efficacy of the clinical protocol. In the concentrations used, there was no statistical difference between the mean daily pain, sedation, nausea and vomiting, and pruritus scores for both opioids (Friedman test). The analysis of variance of the log-total opioid doses per patient during periods 1, 2, and 3 indicated that patients used 27% more hydromorphone than expected from its presumed 7:1 ratio relative to morphine potency used in the PCA infusions. The mean plasma hydromorphone concentration was 4.7 ng/ml (range, 1.9 to 8.9 ng/ml), and the mean clearance was 51.7 ml/min per kilogram of body weight (range, 28.6 to 98.2 ml/min per kilogram). The mean plasma morphine, morphine-6-glucuronide, and morphine-3-glucuronide concentrations were 40.0 ng/ml (range, 15 to 62.5), 168.2 ng/ml (range, 54.4 to 231.9), and 391.0 ng/ml (range, 149.4 to 921.7), respectively. The mean morphine clearance was 34.3 ml/min per kilogram of body weight (range, 19.3 to 58.3). The mean molar ratios of morphine-6-glucuronide/morphine, morphine-3-glucoronide/morphine, and morphine-3-glucuronide/morphine-6-glucuronide were 2.48 (range, 1.4 to 3.3), 5.82 (range, 3.4 to 9.1), and 2.46 (range, 1.1 to 3.3), respectively.\n The safety and efficacy of a clinical protocol for the administration of opioids by means of PCA for mucositis pain after bone marrow transplantation was demonstrated. In this small study, hydromorphone was not superior to morphine in terms of analgesia or the side-effect profile: a larger study would be needed to show a difference. The clearances of hydromorphone and morphine in the children studied were generally greater than those previously recorded, but this finding may be related to disease or treatment variables. Apart from clearance, the morphine pharmacokinetics in the study population were similar to those previously recorded. Hydromorphone may be less potent in this population of children than indicated by adult equipotency tables.", "Tricyclic antidepressants (TCA) provide less than satisfactory pain relief for postherpetic neuralgia (PHN), and the role of opioids is controversial.\n To compare the analgesic and cognitive effects of opioids with those of TCA and placebo in the treatment of PHN.\n Seventy-six patients with PHN were randomized in a double-blind, placebo-controlled, crossover trial. Each subject was scheduled to undergo three treatment periods (opioid, TCA, and placebo), approximately 8 weeks' duration each. Doses were titrated to maximal relief or intolerable side effects. The primary outcome measures were pain intensity (0 to 10 scale), pain relief (0 to 100%), and cognitive function. Analyses included patients who provided any pain ratings after having received at least a single dose of a study medication.\n Fifty patients completed two periods, and 44 patients completed all three. Mean daily maintenance doses were morphine 91 mg or methadone 15 mg and nortriptyline 89 mg or desipramine 63 mg. Opioids and TCA reduced pain (1.9 and 1.4) more than placebo (0.2; p < 0.001), with no appreciable effect on any cognitive measure. The trend favoring opioids over TCA fell short of significance (p = 0.06), and reduction in pain with opioids did not correlate with that following TCA. Treatment with opioids and TCA resulted in greater pain relief (38 and 32%) compared with placebo (11%; p < 0.001). More patients completing all three treatments preferred opioids (54%) than TCA (30%; p = 0.02).\n Opioids effectively treat PHN without impairing cognition. Opioids and TCA act via independent mechanisms and with varied individual effect.", "To evaluate the effectiveness and safety of samarium-153 (153Sm) lexidronam (EDTMP) in a double-blind, placebo-controlled study.\n Patients with painful bone metastases secondary to a variety of primary malignancies were randomized to receive 153Sm-EDTMP 0.5 or 1.0 mCi/kg, or placebo. Treatment was unblinded for patients who did not respond by week 4, with those who had received placebo eligible to receive 1.0 mCi/kg of active drug in an open-label manner. Patient and physician evaluations were used to assess pain relief, as was concurrent change in opioid analgesia.\n One hundred eighteen patients were enrolled onto the study. Patients who received 1.0 mCi/kg of active drug had significant reductions in pain during each of the first 4 weeks in both patient-rated and physician-rated evaluations. Pain relief was observed in 62% to 72% of those who received the 1.O-mCi/kg dose during the first 4 weeks, with marked or complete relief noted in 31% by week 4. Persistence of pain relief was seen through week 16 in 43% of patients who received 1.0 mCi/kg, of active drug. A significant correlation (P = .01) was observed between reductions in opioid analgesic use and pain scores only for those patients who received 1.0 mCi/kg 153Sm-EDTMP. Bone marrow suppression was mild, reversible, and not associated with grade 4 toxicity.\n A single dose of 1.0 mCi/kg of 153Sm-EDTMP provided relief from pain associated with bone metastases. Pain relief was observed within 1 week of administration and persisted until at least week 16 in the majority of patients who responded.", "To evaluate the safety and efficacy of a new slow-release preparation of hydromorphone (SRH) in the treatment of cancer pain.\n Ninety-five adult patients from three Canadian Palliative Care Centers with no evidence of mental impairment received treatment for cancer pain with an oral opioid analgesic. After informed consent was obtained, patients underwent titration to a stable dose of immediate-release hydromorphone (IRH) for 48 hours, and were then randomized to receive IRH or SRH for 5 days in a double-blind basis. During day 6, a crossover took place, and patients received the alternate drug for 5 days. Pain intensity was assessed using a visual analog scale (VAS) and ordinal scale (OS). Side effects were assessed using VAS. Patients and investigators made a blinded global rating of efficacy a blinded final choice between SRH and IRH.\n In 75 assessable patients, pain intensity of the VAS and OS were (mean +/- SD) 27 +/- 21 and 1.3 +/- 0.6 on IRH, versus 29 +/- 21 (P = .13) and 1.3 +/- 0.6 (P = .19) on SRH, respectively. The total number of extra doses of opioids, global rating, and final blinded choice by both patients and investigators were not significantly different between IRH and SRH. Differences in side effects were not significant.\n Our findings suggest that SRH is as safe and effective as IRH in the treatment of cancer pain.", "Amitriptyline is the most common analgesic adjuvant used in cancer patients with neuropathic pain, even though no specific studies have demonstrated a benefit. A randomized placebo-controlled, double-blind crossover study was designed to evidence the effects of amitriptyline in patients with neuropathic cancer pain.\n Sixteen advanced cancer patients with neuropathic pain on systemic morphine therapy, no longer receiving oncologic treatment, presenting moderate pain (about 4 or more, but less than 7, on a numerical scale of 0-10) in the last week, and given a stable morphine dose in the last 2 days were admitted to the study. During the first week of study, patients were administered 25 mg of amitriptyline or equivalent drops of placebo at night for 3 days and 50 mg for the following 4 days. Doses for patients aged more than 65 years were 15 mg (first 3 days) and 30 mg (3 days after). After a week, a crossover took place for the second week, with the other treatment at an inverse sequence. Opioid consumption, pain intensity, symptoms and adverse effects, mood, sleep, patient's preference, quality of life before starting the study, the first week after and the second week after were recorded.\n No significant benefits in analgesia were found in the global pain intensity of the previous week of treatment, the least pain intensity or the pain evaluated just after a week of treatment, at the moment of the visit, when amitriptyline was compared with placebo. A significant difference was evidenced for the worst pain (P < 0.035). No differences in opioid doses during the period of study were found. Drowsiness, confusion and dry mouth were significantly more intense with amitriptyline than with placebo (P < 0.036, 0.003, and 0.034, respectively). There were no substantial differences between the two treatments in Spitzer's quality of life score and for each item. No differences in patients' preference for the two treatment periods were found. The analgesic effects of amitriptyline were slight and associated with adverse effects.\n In light of the results obtained in the study, the extensive use of the drug for cancer pain should be questioned.", "Painful neuropathy is one of the most common long-term complications of diabetes mellitus and often proves difficult to relieve.\n Patients with diabetic neuropathy with moderate or greater pain for at least 3 months, were evaluated for efficacy, safety and health-related quality of life (QOL) while receiving controlled-release (CR) oxycodone (OxyContin) or active placebo. Patients underwent washout from all opioids 2-7 days before randomization to 10 mg CR oxycodone or active placebo (0.25 mg benztropine) q12h. The dose was increased, approximately weekly, to a maximum of 40 mg q12h CR oxycodone or 1 mg q12h benztropine, with crossover to the alternate treatment after a maximum of 4 weeks. Acetaminophen, 325-650 mg q4-6h prn was provided as rescue.\n Thirty-six patients were evaluable for efficacy (21 men, 15 women, mean age 63.0+/-9.4 years). CR oxycodone resulted in significantly lower (P=0.0001) mean daily pain (21.8+/-20.7 vs. 48.6+/-26.6 mm VAS), steady pain (23.5+/-23.0 vs. 47.6+/-30.7 mm VAS), brief pain (21.8+/-23.5 vs. 46.7+/-30.8 mm VAS), skin pain (14.3+/-20.4 vs. 43.2+/-31.3 mm VAS), and total pain and disability (16.8+/-15.6 vs. 25.2+/-16.7; P=0.004). Scores from 6 of the 8 SF-36 domains and both summary scales, Standardized Physical Component (P=0.0002) and Standardized Mental Component (P=0.0338) were significantly better during CR oxycodone treatment. The number needed to treat to obtain one patient with at least 50% pain relief is 2.6 and clinical effectiveness scores favoured treatment with CR oxycodone over placebo (P=0.0001).\n CR oxycodone is effective and safe for the management of painful diabetic neuropathy and improves QOL.", "Forty-three patients with peripheral neuropathic pain, exclusively pain reduced by spinal cord stimulation (SCS), were switched into a painful state after SCS inactivation. This mode was used to assess the pain-relieving effect of carbamazepine (CMZ) and opioids in a double-blinded, placebo-controlled trial. In Phase 1, the patients were randomly allocated to receive either CMZ (600 mg/d) or placebo during an SCS-free period of 8 days. In Phase 2, after a CMZ elimination interval of 7 days, 38 patients received either sustained-release morphine (90 mg/d) or placebo for 8 days. In cases of intolerable pain, the patients were authorized to reactivate their SCS. The pain intensity was rated on a numeric analog scale. In 38 patients who completed Phase 1, significant delay in pain increase was observed in the CMZ group as compared with placebo (P = 0.038). In Phase 2, the trend observed with morphine was insignificant (P = 0.41). Two CMZ patients and one morphine patient showed complete pain relief and preferred to continue the medication. Thirty-five patients returned to SCS. We conclude that CMZ is effective in peripheral neuropathic pain. Morphine obviously requires larger individually titrated dosages than those used in this study for results to be adequately interpreted.", "Intrathecal (IT) opioid therapy is a treatment alternative for patients with severe chronic non-malignant pain. Several uncontrolled retrospective and prospective outcome studies have suggested a benefit in chronic non-malignant pain patients, but uncertainties about patient selection in these studies weaken the results. This study evaluated long-term outcome of IT opioid therapy in chronic non-malignant pain prospectively, and included two comparative groups to improve understanding of selection criteria and relative severity of intrathecal pump recipients (PRs). The study subjects included 38 PRs while the comparative groups included 31 intrathecal candidates who either had an unsuccessful trial, or declined the IT therapy, and another group of 41 newly referred patients. The following data were analyzed at study entry, and at 6 monthly intervals for a 3-year period: Symptom Check List 90 (SLC-90), SF-36 Health survey, Beck Depression Inventory, McGill Pain Questionnaire (short form), Oswestry Disability Index, Pain Drawings and Pain rating on visual analogue scale. Data analysis suggests the study group of PRs had improvements in pain, mood, and function from baseline to 36 months. These same parameters improved among new referrals (less severe patients receiving conservative pain management) while non-recipients significantly worsened. Although PRs improved, they were still worse off at 36 months than new referrals were at baseline. The study showed that when patients with extremely severe pain problems are selected as pump candidates, they will likely improve with the therapy, but their overall severity of pain and symptoms still remains high.", "The discovery of an endogenous opioid-mediated analgesic system has led to the search for its physiological roles and how it might be activated in natural conditions. Environmental and surgical stress and certain forms of transcutaneous electrical stimulation or acupuncture appear to activate this system. Several studies also suggest that this opioid system mediates placebo analgesia. Placebo reduces post-surgical pain in comparison with no treatment, and this analgesia is apparently reversed by the opioid antagonist, naloxone. However, these studies did not indicate whether naloxone and placebo exert their effects by common or by separate mechanisms. By administering hidden infusions of naloxone (in subjects unaware that the medication was being given) separate from the administration of a placebo, we were able to assess the effects of these two treatments independently. We report here evidence that placebo analgesia can occur after blockade of opioid mechanisms by naloxone and that naloxone can produce hyperalgesia independent of the placebo effect. The combined action of these effects is sufficient to explain the reversal of placebo analgesia by naloxone." ]	Short-term studies provide only equivocal evidence regarding the efficacy of opioids in reducing the intensity of neuropathic pain, whereas intermediate-term studies demonstrate significant efficacy of opioids over placebo, which is likely to be clinically important. Reported adverse events of opioids are common but not life threatening. Further randomized controlled trials are needed to establish long-term efficacy, safety (including addiction potential), and effects on quality of life.
CD008873	[ "3755517", "3488384", "11086300", "20412605" ]	[ "Vitamin D supplementation in pregnancy: a controlled trial of two methods.", "Vitamin D supplementation during pregnancy: effect on neonatal calcium homeostasis.", "Vitamin a status of pregnant women and effect of post partum vitamin a supplementation.", "Effect of multiple-micronutrient supplementation on maternal nutrient status, infant birth weight and gestational age at birth in a low-income, multi-ethnic population." ]	[ "A randomized study was conducted to evaluate the effects of single-dose and daily vitamin D supplementation in pregnant women during the last trimester of a winter pregnancy in the Northwest of France. The women were divided into three randomized groups: one (N = 21) was given a vitamin D2 supplement of 1000 IU/day during the last three months of pregnancy, one (N = 27) was given a single oral dose of 5 mg at the seventh month of pregnancy, and one (N = 29) acted as a control. Venous plasma samples were obtained at delivery from the women and from cord blood, and levels of calcium, 25-OHD, and 1,25(OH)2D were determined. No significant difference in plasma calcium concentration was found among the three groups, but within each group plasma calcium concentrations were higher in the cord samples than in the respective maternal samples. The levels of the two metabolites measured were consistently lower in the cord samples than in the respective maternal samples. Cord 25-OHD concentrations correlated with those of maternal plasma. No significant modification of maternal calciuria or of the birth weight of term infants was observed. 25-OHD concentrations were greater in maternal and cord plasma from treated mothers, but only a slight difference was observed between the supplemented groups. 1,25(OH)2D concentrations were not significantly different in the three groups. A single 5-mg dose of vitamin D given orally at the seventh month of pregnancy provides effective prophylaxis in the authors' region.", "We assessed whether modification of vitamin D nutritional status during the last trimester of pregnancy affects maternal and neonatal calcium homeostasis. At the end of the first trimester, 40 pregnant women were randomly assigned to either of two groups, and blood taken to assess the basal values of Ca, Pi, Mg, iPTH, 25-OHD, and 1,25(OH)2D. From the sixth month on, group 1 (+D) received 1000 IU vitamin D3 daily; group 2 (-D) served as control. At the time of delivery, maternal serum 25-OHD was higher in the +D group (P less than 0.0005). Ca, Pi, iPTH, and 1,25(OH)2D were not affected. At term, venous cord 25-OHD levels were also higher in the +D group (P less than 0.0005), and 1,25(OH)2D levels slightly lower (P less than 0.05), but neither Ca, Pi, nor iPTH differed between the two groups. Serum CaT dropped significantly (P less than 0.002) at 4 days of age in the infants from both groups, although to a lesser extent in these from the +D group (P less than 0.05). Circulating iPTH increased in both groups. Serum 25-OHD remained low in the -D group, and dropped slightly in the +D group; 1,25(OH)2D remained stable during the first 4 days of life in the -D group, and increased in the +D group (P less than 0.001). Our data demonstrate the importance of providing adequate maternal vitamin D stores to ensure better perinatal handling of calcium. This is of particular importance for populations at risk for hypovitaminosis D.", "To assess the Vitamin A status of pregnant women in their third trimester using maternal serum retinol levels as the indicator; and (ii) To assess the impact of postpartum Vitamin A supplementation on the Vitamin A status of exclusively breastfed infants.\n Prospective randomized single blind controlled study.\n Teaching Hospital.\n 109 apparently healthy primi and second gravida women registered at the antenatal clinic were included in the study and followed up for three months postpartum. Serum retinol levels of pregnant mothers in their third trimester (35-37 weeks) and cord blood levels after delivery were estimated. Mothers were then assigned to two groups. The experimental group included 53 mothers who received a single dose of 2 lakh units of Vitamin A orally. The control group had 56 mothers who did not receive Vitamin A. Mothers and infants were followed up for three months. The serum retinol of infants and the breast milk retinol levels were estimated at the end of three months and the results were compared. The growth of the infants was also monitored.\n Subclinical Vitamin A deficiency was seen in 29.67% of pregnant women. At the end of three months, 69.6% of mothers in the control group had breast milk retinol levels below 30 mg/dl, as opposed to 36.1% in the experimental group. Forty five per cent of infants in the control group had subclinical vitamin A deficiency compared to none in the experimental group. There was no difference in the growth of infants in the two groups. However, the infant serum and the breast milk retinol levels were significantly higher in the supplemented group.\n There is a high prevalence of inapparent Vitamin A deficiency (29.7%) in pregnant women in their third trimester from lower socio-economic strata. Postpartum Vitamin A supplementation had a beneficial impact on the infant serum retional and the breast milk retinol level but no effect on infant growth.", "Poor nutrient intake during pregnancy can adversely affect both infant and maternal health. The aim was to investigate the efficacy of multiple-micronutrient supplementation during pregnancy in a socially deprived population in the developed world. We conducted a randomised, double-blind, placebo-controlled trial of multiple-micronutrient supplementation including 20 mg Fe and 400 microg folic acid, from the first trimester of pregnancy in 402 mothers, in East London, UK. Nutrient status was measured at recruitment, and at 26 and 34 weeks of gestation. Infants were weighed at birth. At recruitment the prevalence of anaemia was 13 %, vitamin D insufficiency 72 %, thiamin deficiency 12 % and folate deficiency 5 %, with no differences between groups. Only 39 % of women completed the study; rates of non-compliance were similar in both groups. Intention-to-treat analysis showed that participants receiving treatment had higher mean Hb at 26 weeks of gestation (110 (sd 10) v.108 (sd 10) g/l; P = 0.041) and 34 weeks of gestation (113 (sd 12) v.109 (sd 10) g/l; P = 0.003) and packed cell volume concentrations at 26 weeks of gestation (0.330 (sd 0.025) v. 0.323 (sd 0.026) l/l; P = 0.011) and 34 weeks of gestation (0.338 (sd 0.029) v. 0.330 (sd 0.028) l/l; P = 0.014) compared with controls. Analysis of compliant women showed supplemented women had higher median concentrations of serum ferritin, erythrocyte folate and 25-hydroxyvitamin D later in gestation than controls. In the compliant subset (n 149), placebo mothers had more small-for-gestational age (SGA) infants (eight SGA v. thirteen; P = 0.042) than treatment mothers. Baseline micronutrient deficiencies were common; the multiple-micronutrient supplement was well-tolerated and improved nutrient status. Multiple-micronutrient supplements from early pregnancy may be beneficial and larger studies are required to assess impact on birth outcomes and infant development." ]	Vitamin D supplementation in a single or continued dose during pregnancy increases serum vitamin D concentrations as measured by 25-hydroxyvitamin D at term. The clinical significance of this finding and the potential use of this intervention as a part of routine antenatal care are yet to be determined as the number of high quality trials and outcomes reported is too limited to draw conclusions on its usefulness and safety. Further rigorous randomised trials are required to evaluate the role of vitamin D supplementation in pregnancy.
CD001509	[ "2643038", "10601063" ]	[ "The efficacy of endoscopic sphincterotomy after cholecystectomy in patients with sphincter-of-Oddi dysfunction.", "Manometry based randomised trial of endoscopic sphincterotomy for sphincter of Oddi dysfunction." ]	[ "Forty-seven patients thought to have dysfunction of the sphincter of Oddi were randomly assigned to undergo endoscopic sphincterotomy or sham sphincterotomy in a prospective double-blind study. All the patients had pain resembling biliary pain, had previously undergone a cholecystectomy, and had clinical characteristics suggesting biliary obstruction. The patients were randomly assigned to the treatment (n = 23) or nontreatment (n = 24) group before manometric examination of the sphincter of Oddi was performed. Sphincterotomy resulted in improvement in pain scores at one-year follow-up in 10 of 11 patients with elevated sphincter pressure. In contrast, there was improvement in only 3 of 12 patients with elevated basal sphincter pressures who underwent the sham procedure. In patients with normal sphincter pressure, pain scores were similar regardless of treatment. After one year, sphincterotomy was performed in 12 symptomatic patients who had undergone the sham procedure--7 with elevated sphincter pressures and 5 with normal sphincter pressures. Forty patients were followed for four years. Of the 23 patients with increased sphincter pressure, 10 of the original 11 who underwent sphincterotomy remained virtually free of pain; 7 others who subsequently underwent sphincterotomy also benefited from it. Thus, 17 of 18 patients with sphincter-of-Oddi dysfunction verified by manometry benefited from sphincterotomy. In patients with normal sphincter pressure, sphincterotomy was no more beneficial than sham therapy. Our observations suggest that endoscopic sphincterotomy offers long-term relief of pain in a group of patients with verified sphincter-of-Oddi dysfunction.", "Endoscopic sphincterotomy for biliary-type pain after cholecystectomy remains controversial despite evidence of efficacy in some patients with a high sphincter of Oddi (SO) basal pressure (SO stenosis).\n To evaluate the effects of sphincterotomy in patients randomised on the basis of results from endoscopic biliary manometry.\n Endoscopic biliary manometry was performed in 81 patients with biliary-type pain after cholecystectomy who had a dilated bile duct on retrograde cholangiography, transient increases in liver enzymes after episodes of pain, or positive responses to challenge with morphine/neostigmine. The manometric record was categorised as SO stenosis, SO dyskinesia, or normal, after which the patient was randomised in each category to sphincterotomy or to a sham procedure in a prospective double blind study. Symptoms were assessed at intervals of three months for 24 months by an independent observer, and the effects of sphincterotomy on sphincter function were monitored by repeat manometry after three and 24 months.\n In the SO stenosis group, symptoms improved in 11 of 13 patients treated by sphincterotomy and in five of 13 subjected to a sham procedure (p = 0.041). When manometric records were categorised as dyskinesia or normal, results from sphincterotomy and sham procedures did not differ. Complications were rare, but included mild pancreatitis in seven patients (14 episodes) and a collection in the right upper quadrant, presumably related to a minor perforation. At three months, the endoscopic incision was extended in 19 patients because of manometric evidence of incomplete division of the sphincter.\n In patients with presumed SO dysfunction, endoscopic sphincterotomy is helpful in those with manometric features of SO stenosis." ]	These results suggest that sphincterotomy for biliary sphincter of Oddi dysfunction appears effective in those patients with an elevated sphincter of Oddi basal pressure (>40 mmHg), but is no better than placebo in those patients with a normal basal pressure. The results reported in this review must be interpreted with caution as there are only two studies and one of the reviewers (Toouli) has been an author in both studies. Further trials by independent groups are recommended.
CD006431	[ "20599196", "9236641" ]	[ "Uterine massage to reduce postpartum hemorrhage after vaginal delivery.", "Routine oxytocin in the third stage of labour: a placebo controlled randomised trial." ]	[ "To determine the effectiveness of sustained uterine massage started before delivery of the placenta in reducing postpartum hemorrhage.\n A randomized controlled trial conducted in Egypt and South Africa between September 2006 and February 2009. A total of 1964 pregnant women were randomly allocated to 1 of 3 treatment groups: intramuscular oxytocin, sustained uterine massage, or both treatments. Blood loss within 30 minutes of delivery was recorded.\n The incidence of blood loss of 300 mL or more within 30 minutes of delivery was significantly higher in the massage group than in the massage plus oxytocin (RR 1.88; 95% CI, 1.29-2.74 in Assiut, and RR 1.3; 95% CI, 1.00-1.68 in SA) and the oxytocin only group (RR 1.7; 95% CI, 1.11-2.61 in Assiut, and RR 2.24; 95% CI, 1.54-3.27 in SA). In both centers, use of additional uterotonics was significantly higher in the uterine massage group compared with the other 2 groups.\n Uterine massage was less effective than oxytocin for reducing blood loss after delivery. When oxytocin was used, there was no additional benefit from uterine massage. The effectiveness of uterine massage in the absence of oxytocin was not studied. ACTRN: 12609000372280.\n Copyright © 2010 International Federation of Gynecology and Obstetics. Published by Elsevier Ireland Ltd. All rights reserved.", "To compare intravenous oxytocin administration (Partocon 10 IU) with saline solution in the management of postpartum haemorrhage in the third stage of labour.\n A double-blind, randomised controlled trial involving 1000 parturients with singleton fetuses in cephalic presentation and undergoing vaginal delivery, randomly allocated to treatment with oxytocin (n = 513) or 0.9% saline solution (n = 487).\n Labour ward at a central county hospital.\n Mean blood loss (total, and before and after placenta delivery); frequencies of blood loss > 800 mL, need of additional oxytocic treatment, postpartum haemoglobin < 10 g/dL; and duration of postpartum hospitalisation.\n As compared with saline solution, oxytocin administration was associated with significant reduction in mean total blood loss (407 versus 527 mL), and in frequencies of postpartum haemorrhage > 800 mL (8.8% versus 5.2%), additional treatment with metylergometrine (7.8% versus 13.8%), and postpartum Hb < 10 g/dL (9.7% versus 15.2%), and a nonsignificant increase in the frequency of manual placenta removal (3.5% versus 2.3%). There was no group difference in the mean duration of postpartum hospitalisation (4.6 versus 4.5 days, respectively).\n Administration of intravenous oxytocin in the third stage of labour is associated with an approximately 22% reduction in mean blood loss, and approximately 40% reductions in frequencies of postpartum haemorrhage (> 500 mL or > 800 mL) and of postpartum haemoglobin < 10 g/dL. Identification of risk groups for oxytocin treatment does not seem worthwhile. Oxytocin is a cheap atoxic drug and should be given routinely after vaginal delivery." ]	The results of this review are inconclusive, and should not be interpreted as a reason to change current practice. Due to the limitations of the included trials, more trials with sufficient numbers of women are needed in order to estimate the effects of sustained uterine massage. All the women compared in this review received oxytocin as part of the active management of labour. Recent research suggests that once an oxytocic has been given, there is limited scope for further reduction in postpartum blood loss. Trials of uterine massage in settings where uterotonics are not available, and which measure women's experience of the procedure, are needed.
CD006233	[ "16401473", "12241833", "2197836", "12145577", "776322" ]	[ "Cholecystectomy or gallbladder in situ after endoscopic sphincterotomy and bile duct stone removal in Chinese patients.", "Wait-and-see policy or laparoscopic cholecystectomy after endoscopic sphincterotomy for bile-duct stones: a randomised trial.", "Elective cholecystectomy without drainage and without prophylactic antibiotics. A prospective randomized trial with clinical and bacteriological aspects.", "Laparoscopic common bile duct exploration and cholecystectomy versus endoscopic stone extraction and laparoscopic cholecystectomy for choledocholithiasis. A prospective randomized study.", "A controlled trial of drainage after cholecystectomy." ]	[ "In patients with stones in their bile ducts and gallbladders, cholecystectomy is generally recommended after endoscopic sphincterotomy and clearance of bile duct stones. However, only approximately 10% of patients with gallbladders left in situ will return with further biliary complications. Expectant management is alternately advocated. In this study, we compared the treatment strategies of laparoscopic cholecystectomy and gallbladders left in situ.\n We randomized patients (>60 years of age) after endoscopic sphincterotomy and clearance of their bile duct stones to receive early laparoscopic cholecystectomy or expectant management. The primary outcome was further biliary complications. Other outcome measures included adverse events after cholecystectomy and late deaths from all causes.\n One hundred seventy-eight patients entered into the trial (89 in each group); 82 of 89 patients who were randomized to receive laparoscopic cholecystectomy underwent the procedure. Conversion to open surgery was needed in 16 of 82 patients (20%). Postoperative complications occurred in 8 patients (9%). Analysis was by intention to treat. With a median follow-up of approximately 5 years, 6 patients (7%) in the cholecystectomy group returned with further biliary events (cholangitis, n = 5; biliary pain, n = 1). Among those with gallbladders in situ, 21 (24%) returned with further biliary events (cholangitis, n = 13; acute cholecystitis, n = 5; biliary pain, n = 2; and jaundice, n = 1; log rank, P = .001). Late deaths were similar between groups (cholecystectomy, n = 19; gallbladder in situ, n = 11; P = .12).\n In the Chinese, cholecystectomy after endoscopic treatment of bile duct stones reduces recurrent biliary events and should be recommended.", "Patients who undergo endoscopic sphincterotomy for common bile-duct stones, who have residual gallbladder stones, are referred for laparoscopic cholecystectomy. However, only 10% of patients who do not have this operation are reported to develop recurrent biliary symptoms. We aimed to assess whether a wait-and-see policy is justified.\n We did a prospective, randomised, multicentre trial in 120 patients (age 18-80 years) who underwent endoscopic sphincterotomy and stone extraction, with proven gallbladder stones. Patients were randomly allocated to wait and see (n=64) or laparoscopic cholecystectomy (56). Primary outcome was recurrence of at least one biliary event during 2-year follow-up, and secondary outcomes were complications of cholecystectomy and quality of life. Analysis was by intention to treat.\n 12 patients were lost to follow-up immediately. Of 59 patients allocated to wait and see, 27 (47%) had recurrent biliary symptoms compared with one (2%) of 49 patients after laparoscopic cholecystectomy (relative risk 22.42, 95% CI 3.16-159.14, p<0.0001). 22 (81%) of 27 patients underwent cholecystectomy, mainly for biliary pain (n=13) or acute cholecystitis (7). Conversion rate to open surgery was 55% in patients allocated to wait and see who underwent cholecystectomy compared with 23% in those who were allocated laparoscopic cholecystectomy (p=0.0104). Morbidity was 32% versus 14% (p=0.1048), and median hospital stay was 9 versus 7 days. Quality of life returned to normal within 3 months after either treatment policy.\n A wait-and-see policy after endoscopic sphincterotomy in combined cholecystodocholithiasis cannot be recommended as standard treatment, since 47% of expectantly managed patients developed at least one recurrent biliary event and 37% needed cholecystectomy. No major biliary complications arose, but conversion rate was high.", "A consecutive series of 50 patients undergoing elective cholecystectomy without prophylactic antibiotics entered a prospective randomized trial to compare the post-operative clinical course whether the subhepatic space was drained or not. 26 patients (mean age 58 yrs) were drained and 24 patients (mean age 59 yrs) were not. The incidence of positive gallbladder bile cultures were respectively 8 and 19% (N.S.) in the drained and undrained groups. The incidence of post-operative mortality, thrombo-phlebitis and intra-abdominal sepsis was zero in both groups. In the drained or undrained series, the incidence of wound infection was respectively 4% and 0% (N.S.), that of urinary infection was 8% and 13% (N.S.) and that of pulmonary atelectasis was 15 and 17% (N.S.). A further consecutive series of 100 undrained elective cholecystectomies (18% positive bile cultures) without prophylactic antibiotics was then performed with the same uneventful postoperative course. This study therefore indicates that even in the presence of bacterobilia elective cholecystectomy can be safely performed without subhepatic space drainage and without prophylactic antibiotics.", "Our objective is to compare the results of laparoscopic cholecystectomy (LC) and common bile duct (CBD) exploration to those of endoscopic stone extraction and LC in patients with CBD lithiasis based on a prospective randomized study.\n From April 1997 until August 2000, 78 patients were assigned in two groups. Group A (n'36) patients underwent laparoscopic either direct or trancystic duct, CBD exploration and LC. Group B (n'42) patients were referred for endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (ES) for duct clearance and at a later stage LC was performed. Selection of patients of both groups was done, considering prognostic factors of a preliminary study.\n Laparoscopic duct clearance was achieved in 85.7% of patients while the respective percentage for the combined approach was 84.3%.\n Laparoscopic CBD exploration is not yet established as the gold standard procedure for choledocholithiasis and there is the need for further randomized trials and possibly future meta-analyses.", "A prospective controlled trial of drainage after cholecystectomy has been carried out. In a consecutive series of 143 patients undergoing cholecystectomy, 50 patients were randomly allocated to a drainage group and a further 50 patients to a non-drainage group. The remaining 43 patients were drained electively because the common bile duct was explored or because of infection or incomplete haemostasis. There was no significant difference in the incidence of wound infection or other complications between the drainage and the non-drainage groups. The duration of postoperative pyrexia, the number of analgesic injections and the length of postoperative hospital stay were the same in both the randomized groups. One patient in the randomized drainage group had a reactionary haemorrhage from the drain site requiring transfusion. There was no mortality but one patient in the elective drainage group had to be re-explored for a subhepatic abscess. Three patients in this group drained bile from the drain for 3-9 days but all had a T tube in place. This trial fails to demonstrate any advantage or disadvantage in draining the gallbladder bed after cholecystectomy." ]	Prophylactic cholecystectomy should be offered to patients whose gallbladders remain in-situ after endoscopic sphincterotomy and common bile duct clearance.
CD005257	[ "2266671", "15523183", "9487416" ]	[ "Albuterol and insulin for treatment of hyperkalemia in hemodialysis patients.", "Special management of insulin lispro in continuous subcutaneous insulin infusion in young diabetic children: a randomized cross-over study.", "Treatment of hyperkalaemia by altering the transcellular gradient in patients with renal failure: effect of various therapeutic approaches." ]	[ "We evaluated in maintenance hemodialysis patients the potassium lowering effects of intravenous insulin with glucose, nebulized albuterol, and a regimen combining both modalities. There was a similar decrease in plasma potassium following either insulin with glucose (0.65 +/- 0.09 mmol/liter) or albuterol (0.66 +/- 0.12 mmol/liter), and a substantially greater fall with the combined regimen (1.21 +/- 0.19 mmol/liter, P less than 0.02 vs. either drug alone). Baseline plasma glucose concentrations were similar (about 4.8 mmol/liter) prior to all three treatments. Following insulin with glucose, plasma glucose increased transiently. but then fell to 2.8 +/- 0.3 mmol/liter at one hour, with concentrations below 3 mmol/liter in 9 of 12 patients. None of the patients had symptoms of hypoglycemia. Plasma glucose increased to 6.8 +/- 0.5 mmol/liter with albuterol. After the combined drug regimen plasma glucose rose transiently and was back to baseline (4.7 +/- 0.7 mmol/liter) at one hour. Treatment with insulin or albuterol produced trivial increases in heart rate, whereas the combined drug regimen was associated with a significant rise (15.1 +/- 6.0 min-1). These observations suggest that albuterol and insulin with glucose are equally efficacious in lowering plasma potassium in uremic patients, and that the hypokalemic effects of the two drugs is additive. The hypoglycemic effect of insulin is attenuated by coadministration albuterol. Combined therapy with insulin, glucose and albuterol is efficacious and safe for the acute treatment of hyperkalemia in hemodialysis patients.", "To compare the safety, efficacy and management of insulin lispro (LP) with regular human insulin (RH) in young diabetic children treated with continuous subcutaneous insulin infusion (CSII).\n 27 very young diabetic children (age 4.6 +/- 2.2 years) treated with CSII participated in an open-label, randomized cross-over multicenter study comparing 2 periods of 16 weeks of CSII with LP or RH.\n Mean daily basal rate was significantly higher during the LP period (p = 0.04). No differences were seen in changes in HbA1c levels, number of hypoglycemic events, cutaneous infections and catheter occlusions. There was no significant difference between the two treatments for preprandial and postprandial glucose values, although prandial glucose excursions tended to be lower with LP (significant at dinner, p = 0.01). Mean blood glucose levels were significantly higher at 0.00 and 3.00 a.m. during LP therapy (p < 0.05). No episode of ketoacidosis occurred during LP treatment. More parents indicated that LP made their own and the child's daily life easier (p = 0.02) and preferred LP (p = 0.01).\n LP in CSII therapy in children is safe, as effective as RH, improved postprandial excursions, met the needs of young children in their daily life well, and gained their parents' satisfaction and preference. However, a shorter duration of LP resulted in hyperglycemia during the first part of the night, which must be compensated for by increasing nocturnal basal rates during this time.", "Ten patients with acute and 60 with chronic renal failure (both groups having hyperkalaemia), were managed at Kenyatta National Hospital in the medical wards and Renal Unit between August, 1995 and January, 1996. They were divided into seven different treatment groups, each consisting of ten patients. Treatment A glucose 25g i.v. with insulin 10 units i.v., treatment B 50 mmol of 8.4% sodium bicarbonate infusion, treatment C 0.5mg of salbutamol i.v. in 50mls 5% dextrose, treatment D was a combination of treatments A and B, treatment E was a combination of treatment B and C, treatment F was a combination of treatments A and C while treatment G was a combination of treatments A and B and C. Serum potassium was measured, 30 minutes, 1 hour, 2 hours, 4 hours and 8 hours after treatment. Plasma glucose concentration was measured before treatment was given and 1 hour after in all patients. Electrocardiography was done before treatment on all patients and repeated 30 minutes and 1 hour after treatment for the patients with hyperkalaemic changes on the initial recording. All treatment modalities had satisfactory potassium lowering effects. Of the single therapeutic approaches, treatment A and C were equieffective, but better than treatment B (P < 0.001). Amongst the two regimen combinations, treatment D and F were more efficacious than treatment E and all the single therapeutic approaches (P < 0.001). Treatment G was the most efficacious in lowering serum potassium in this study. All treatment modalities had maximum serum potassium lowering effect at 1-2 hours. A fall in plasma glucose concentration was a notable feature of treatments A and D, but significant hypoglycaemia occurred in 20% of patients receiving treatment A and in none on treatment D. The ECG changes of hyperkalaemia did not correlate with serum potassium levels. The normalisation of hyperkalaemic ECG alteration occurred within the first 30 minutes after treatment. In conclusion, combination therapies for hyperkalaemia appear to be more efficacious than single therapeutic approaches. Inclusion of salbutamol seems to protect against insulin induced hypoglycaemia. The maximum potassium lowering effect is observed 1-2 hours of administration of either agents. The potassium reducing effect remains significant compared to baseline values even after 8 hours. If dialysis cannot be instituted early enough it seems reasonable to repeat treatment every 4-6 hours to sustain the effect. Repeated administration of glucose with insulin may not be safe because of the hypoglycaemic effect. Other single and combination therapies can theoretically be repeated regularly until dialysis is initiated although this requires further clinical evaluation." ]	In view of the limited information from small studies of uncertain quality, no firm recommendations for clinical practice can be made. It appears that the combination of insulin and glucose is preferred over treatment with rectal cation-resin for hyperkalaemia in preterm infants. Both the combination of insulin and glucose and albuterol inhalation deserve further study. The two interventions could possibly be tested against each other. The effectiveness of other potentially effective interventions for non-oliguric hyperkalaemia (diuretics, exchange transfusion, peritoneal dialysis and calcium) have not been tested in randomised controlled trials.
CD004028	[ "16190799", "17148938", "16754835", "786416", "17625502" ]	[ "A double-blind, placebo-controlled study of valproate for aggression in youth with pervasive developmental disorders.", "A placebo-controlled trial of valproate for agitation and aggression in Alzheimer's disease.", "Atypical antipsychotic agents in the treatment of violent patients with schizophrenia and schizoaffective disorder.", "Effect of sodium valproate on tardive dyskinesia.", "Efficacy and safety of donepezil in patients with schizophrenia or schizoaffective disorder: significant placebo/practice effects in a 12-week, randomized, double-blind, placebo-controlled trial." ]	[ "The aim of this study was to study valproate efficacy and safety for aggression in children and adolescents with pervasive developmental disorders (PDD).\n In this prospective double-blind, placebo-controlled study, 30 subjects (20 boys, 10 girls) 6-20 years of age with PDD and significant aggression were randomized and received treatment with valproate (VPA) or placebo (PBO) for 8 weeks as outpatients. Mean VPA trough blood levels were 75.5 mcg/mL at week 4 and 77.8 mcg/mL at week 8.\n No treatment difference was observed statistically between VPA and PBO groups. The Aberrant Behavior Checklist--Community Scale (ABC-C) Irritability subscale was the primary outcome measure (p = 0.65), and CGI--Improvement (p = 0.16) and OAS (p = 0.96) were secondary outcome measures. Increased appetite and skin rash were significant side effects. Only 1 subject was dropped from the study owing to side effects, notably a spreading skin rash, which then resolved spontaneously. Two subjects receiving VPA developed increased serum ammonia levels, one with an associated parent report of slurred speech and mild cognitive slowing. Poststudy, of 16 VPA and PBO subjects receiving VPA, 10 subjects demonstrated sustained response, 4 of whom later attempted taper, with significant relapse of aggression.\n The present negative findings cannot be viewed as conclusive, partly owing to the large placebo response, subject heterogeneity, and size of the groups. Larger studies are needed to expand upon these findings.", "To assess the efficacy and tolerability of valproate for the treatment of agitation and aggression in moderate-to-severe Alzheimer's disease (AD).\n This was a randomized, double-blind, placebo-controlled crossover trial of valproate in institutionalized AD patients. Patients were assessed with the Neuropsychiatric Inventory (NPI) and Cohen-Mansfield Agitation Inventory at baseline and after 6 weeks of treatment with valproate and placebo, with 2 weeks between phases to allow for placebo washout and tapering.\n Fourteen patients (8 male/6 female) aged 85.6 +/- 4.5 years with baseline Mini Mental State Examination scores of 4.5 +/- 4.6 and NPI agitation/aggression scores of 6.4 +/- 3.5 were randomized to treatment. NPI agitation/aggression treatment change scores significantly worsened during valproate treatment compared with placebo (Z = -2.03, p = 0.04). Tolerability of valproate was also poor, with patients experiencing a significantly greater mean number of adverse events during valproate therapy compared to placebo (Z = -2.82, p = 0.005).\n Valproate is not effective for the management of agitation in moderate-to-severe AD, and may be poorly tolerated in this population.\n Copyright (c) 2007 S. Karger AG, Basel.", "Violent behavior of patients with schizophrenia prolongs hospital stay and interferes with their integration into the community. Finding appropriate treatment of violent behaviors is of primary importance.\n To compare the efficacy of 2 atypical antipsychotic agents, clozapine and olanzapine, with one another and with haloperidol in the treatment of physical assaults and other aggressive behaviors in physically assaultive patients with schizophrenia and schizoaffective disorder.\n Randomized, double-blind, parallel-group, 12-week trial. Physically assaultive subjects with schizophrenia or schizoaffective disorder who were inpatients in state psychiatric facilities were randomly assigned to treatment with clozapine (n = 37), olanzapine (n = 37), or haloperidol (n = 36).\n Number and severity of physical assaults as measured by the Modified Overt Aggression Scale (MOAS) physical aggression score and the number and severity of all aggressive events as measured by the MOAS overall score. Psychiatric symptoms were assessed through the Positive and Negative Syndrome Scale (PANSS).\n Clozapine was superior to both olanzapine and haloperidol in reducing the number and severity of physical assaults as assessed by the MOAS physical aggression score and in reducing overall aggression as measured by the MOAS total score. Olanzapine was superior to haloperidol in reducing the number and severity of aggressive incidents on these 2 MOAS measures. There were no significant differences among the 3 medication groups in improvement of psychiatric symptoms as measured by the PANSS total score and the 3 PANSS subscales.\n Clozapine shows greater efficacy than olanzapine and olanzapine greater efficacy than haloperidol in reducing aggressive behavior. This antiaggressive effect appears to be separate from the antipsychotic and sedative action of these medications.", "The effect of sodium valproate, a drug which has been demonstrated to increase gamma-aminobutyric acid levels in the CNS, on tardive dyskinesia and psychiatric symptoms was investigated in a double-blind cross-over study on 32 chronic psychiatric patients. The oro-facial dyskinesias were totally or significantly relieved in 17 cases. During the active treatment period the involuntary movements of the extremities and dystonic spasms were also significantly relieved in 7 out of 9 patients. In two patients, however, the extrapyramidal symptoms became slightly worse. A significant improvement was noted in the psychiatric symptoms of 14 out of 32 patients during sodium valproate administration. The psychiatric state of 4 out of 32 patients deteriorated. Three was no correlation between the serum concentration of sodium valproate and its effect on the dyskinesia or on the psychiatric symptoms. Some of the elderly subjects showed a slight accumulation of the drug.", "Altered expression of central muscarinic and nicotinic acetylcholine receptors in hippocampal and cortical regions may contribute to the cognitive impairment exhibited in patients with schizophrenia. Increasing cholinergic activity through the use of a cholinesterase inhibitor (ChEI) therefore represents a possible strategy for cognitive augmentation in schizophrenia. We examined the efficacy and safety of the ChEI donepezil as cotreatment for mild to moderate cognitive impairment in schizophrenia or schizoaffective disorder in a prospective, 12-week, placebo-controlled, double-blind, parallel-group study. In total, 250 patients (18-55 years) with schizophrenia or schizoaffective disorder who were clinically stabilized on risperidone, olanzapine, quetiapine, ziprasidone, or aripiprazole, alone or in combination, were enrolled at 38 outpatient psychiatric clinics in the United States. Patients were randomized to donepezil 5 mg q.d. for 6 weeks then 10 mg q.d. for 6 weeks, or placebo administered as oral tablets. The primary outcome measure was the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) neurocognitive battery composite score. In the intent-to-treat sample (donepezil, n=121; placebo, n=124), both treatments showed improvement in the composite score from baseline to week 12. At week 12, cognitive improvement with donepezil was similar to that with placebo (last-observation-carried-forward effect size, 0.277 vs 0.411; p=0.1182) and statistically significantly inferior for the observed-cases analysis (0.257 vs 0.450; p=0.044). There was statistically significant improvement in the Positive and Negative Syndrome Assessment Scale negative symptoms score for placebo compared with donepezil, while total and positive symptom scores were similar between both treatments. Statistically significant improvements in positive symptoms score and Clinical Global Impression-Improvement for donepezil compared with placebo were noted at Week 6. Treatment-emergent adverse events (AEs) were observed for 54.5% of donepezil- and 61.3% of placebo-treated patients; most AEs were rated as mild to moderate in severity. Donepezil was safe and well-tolerated but was not effective compared with placebo as a cotreatment for the improvement of cognitive impairment in this patient population. A significant and surprisingly large placebo/practice effect was observed among placebo-treated patients, and is a serious consideration in future clinical trial study designs for potential cognitive enhancing compounds in schizophrenia." ]	Based on currently available randomised trial-derived evidence, there are no data to support or to refute valproate as a sole agent for schizophrenia. There is some evidence for positive effects on aggression and tardive dyskinesia, but given that these results were based on only a single small study they cannot be considered robust. Given the paucity of the available database further large, simple well-designed and reported trials are necessary. Ideally these would focus on people with schizophrenia and aggression, on those with treatment resistant forms of the disorder and on those with schizoaffective disorders.
CD001835	[ "16130206", "14560224", "19118733" ]	[ "Comparison of surveillance vs Aortic Endografting for Small Aneurysm Repair (CAESAR) trial: study design and progress.", "Quality of life, impotence, and activity level in a randomized trial of immediate repair versus surveillance of small abdominal aortic aneurysm.", "Fit patients with small abdominal aortic aneurysms (AAAs) do not benefit from early intervention." ]	[ "The CAESAR Trial aims to assess the outcome of endovascular repair (EVAR) vs surveillance of small abdominal aortic aneurysms (AAA) with maximum diameter of 4.1-5.4 cm on computerised tomography (CT) scan.\n Patients between 50 and 80 years of age, with small AAA, anatomically suitable for EVAR, are randomly allocated to early EVAR or surveillance. The primary outcome measure is survival. Secondary endpoints include: aneurysm-related deaths (defined as any death caused directly or indirectly by rupture or endovascular/open aneurysm repair), AAA rupture, peri-operative or late complications, conversion to open repair, complications associated with delayed treatment including loss of treatment options, AAA growth rates and quality of life. Target recruitment is 740 patients to show that early EVAR is associated with a 15% survival benefit at 54 months.\n Randomization started in September 2004. By the end of April 2005, 86 patients had been enrolled by 10 active European centres. Completion of recruitment is expected for September 2006 and publication of the results in mid 2007.", "We compared long-term health-related quality-of-life outcome after randomization to immediate elective repair or imaging surveillance, and in relation to time of elective repair, in patients with small asymptomatic abdominal aortic aneurysm (AAA).\n This randomized clinical trial was carried out in 16 Veterans Affairs medical centers. Study subjects were patients at good surgical risk, aged 50 to 79 years, with AAAs 4.0 to 5.4 cm in diameter. Interventions included immediate open surgical AAA repair or imaging surveillance every 6 months with repair reserved for AAAs that became symptomatic or enlarged to 5.5 cm. Main outcome measures considered were SF-36 health status questionnaire, prevalence of impotence, and maximum activity level, which were determined at randomization and at all follow-up visits.\n Eleven hundred thirty-six patients were randomized and followed up for 3.5 to 8 years (mean, 4.9 years). The two randomized groups did not differ significantly for most SF-36 scales at most times, but the immediate repair group scored higher overall in general health (P <.0001), which was particularly evident in the first 2 years after randomization, and slightly lower in vitality (P <.05). The baseline value of one SF-36 scale, physical functioning, was an independent predictor of mortality. Overall, more patients became impotent after randomization to immediate repair compared with surveillance (P <.03), but this difference did not become apparent until more than 1 year after randomization. Maximum activity level did not differ significantly between the two randomized groups, but decline over time was significantly greater in the immediate repair group (P <.02).\n For most quality-of-life measures and times there was no difference between randomized groups. Immediate repair resulted in a higher prevalence of impotence more than 1 year after randomization, but was also associated with improved perception of general health in the first 2 years.", "The UK Small Aneurysm Trial (UKSAT) and the American Aneurysm Detection and Management (ADAM) trial both concluded that early elective open surgery does not confer any late survival advantage in patients with small abdominal aortic aneurysm (AAA) with diameter 4.0 to 5.5 cm. However, two trials of endovascular aneurysm repair in small AAA have started based upon speculation that a sub-group of particularly fit patients, with low operative mortality, may benefit from early intervention. Here we investigate whether the fittest patients from the UKSAT might have benefited from early intervention.\n A total of 1090 patients randomized into the UKSAT between 1991 and 1995 were followed for an average of 12 years for mortality. Baseline data were used to calculate the Customized Probability Index (CPI), a validated prognostic risk score for operative mortality after elective open aneurysm repair that assigns risk points for history of cardiac, pulmonary, and renal disease and subtracts risk points for use of statins and beta-blockers. Cox regression was used to assess any differences in all-cause or aneurysm-related mortality between policies of early surgery or surveillance across the fitness spectrum. Tests for interaction used CPI scores as a continuous variable but patients also were stratified into tertile groups for descriptive purposes. Hazard ratios were adjusted for age, gender, and aneurysm diameter.\n A total of 714 deaths (95 aneurysm-related) occurred in 8485 person-years (number of patients multiplied by average years of conditional follow-up). The mean (standard deviation [SD]) CPI score was 8.1 (9.9) with similar scores between randomized groups. The tertile groups had mean (SD) scores of -1.8 (3.7) for the 389 fittest patients, 8.8 (3.3) for the 438 moderately fit, 21.4 (6.6) for the 261 least fit with missing scores in 2 patients. The tests for interaction were non-significant for both all-cause (P = .176) and aneurysm-related mortality (.178). However, for the least fit patients a survival advantage was seen in the early surgery group; adjusted hazard ratios 0.73 (95% confidence interval [CI] 0.56-0.96) and 0.46 (95% CI 0.22-0.98) for all-cause and aneurysm-related mortality respectively.\n Early elective surgery did not confer any survival benefit in the fittest patients. On the contrary, the possibility of a survival benefit from early intervention in patients of poor fitness merits further investigation through meta-analysis or validation in other prospective studies." ]	The results from the four trials to date demonstrate no advantage to early repair (via open or endovascular surgery) for small AAA (4.0 to 5.5 cm) and suggest that 'best care' for these patients favours surveillance. Furthermore, the more recent trials focused on the efficacy of endovascular aneurysm repair and still failed to show benefit. Thus, both open and endovascular repair of small AAAs are not supported by currently available evidence.
CD000068	[ "395519", "2529770", "1386029" ]	[ "Medical treatment of endometriosis: a comparative trial.", "Buserelin versus danazol in the treatment of endometriosis-associated infertility.", "An open randomized comparative study of the effect of goserelin depot and danazol in the treatment of endometriosis. Zoladex Endometriosis Study Team." ]	[ "In a comparison of danazol, and mestranol with norethynodrel (Enavid, Searle) in the treatment of endometriosis danazol was shown to be superior. Danazol is however relatively ineffective when large tumours or extensive adhesions are present and such patients will usually need a surgical operation. Women who have completed their families and who have severe symptoms will be better treated by hysterectomy. Treatment with danazol is indicated for young women with mild or moderate endometriosis. Danazol treatment may also be given postoperatively after conservative operations.", "A total of 62 infertile women with a laparoscopic diagnosis of endometriosis were allocated randomly to two treatment groups, one of which (32 patients) received oral danazol 600 micrograms/day and the other (30 patients) received intranasal buserelin 1200 micrograms/day for 6 months. Suppression of serum levels of estradiol was greater with the gonadotropin-releasing hormone agonist treatment. Pain symptoms improved markedly during treatment in both groups. At the end of treatment a repeat laparoscopy was performed only in the patients who agreed to it (12 in the buserelin group and 13 in the danazol group), and it did not reveal significant differences in the effects of the two treatments on the endometriotic implants. All of the patients were followed up for at least 12 months, during which pregnancy was attempted. At 18 months the cumulative pregnancy rate was 48% in the patients treated with buserelin and 43% in those treated with danazol. Pain recurrence was observed in about half of the patients in each group 1 year after treatment suspension. The side effects were more frequent and more severe in the danazol-treated patients, whereas those given buserelin generally reported only symptoms of hypoestrogenism. The results of this study suggests that buserelin is at least as effective as danazol in the treatment of endometriosis when the outcome is considered in terms of restored fertility, and its side effects are less severe.", "To compare the efficacy and safety of goserelin depot and danazol for endometriosis.\n Open, randomized comparative trial.\n Multicenter European academic clinical institutions.\n A total of 307 patients with laparoscopically diagnosed endometriosis were randomized to goserelin (n = 204) or danazol (n = 103); 249 patients underwent second look laparoscopy (175 received goserelin and 74 danazol) and were analyzed for efficacy.\n A 3.6-mg depot of goserelin monthly subcutaneously or oral danazol 200 mg three times a day administered for 24 weeks.\n Efficacy assessments were based on changes in visible deposits at laparoscopy before and after treatment and subjective symptom scores at 4-week intervals during treatment and 8-week intervals after treatment for up to 24 weeks. Safety was assessed by adverse event reporting and clinical laboratory measures.\n There were similar proportions of symptomatic (73%) and asymptomatic (but infertile) (27%) and comparable distribution of different severity of endometriosis randomized to each treatment. Significantly fewer patients randomized to goserelin (6.4%) withdrew during treatment compared with 20.4% randomized to danazol (P less than 0.05). There were significantly reduced visible deposits of endometriosis found post-treatment (P less than 0.0001) within each group but no differences between the treatments. The mean total subjective symptoms scores remained significantly less than entry at 24 weeks post-treatment (P less than 0.05). Hypoestrogenic side effects were more common in those receiving goserelin, particularly hot flushes, but anabolic/androgenic side effects of weight gain and muscle cramps were more common in those receiving danazol.\n The monthly administered 3.6-mg depot preparation of goserelin was highly effective at inducing resolution of endometriotic implants and relieving the symptoms of endometriosis with prevention of their return during 24 weeks follow-up in the majority of patients. However, results were not significantly different from those achieved with danazol 600 mg/d." ]	Danazol is effective in treating the symptoms and signs of endometriosis. However, its use is limited by the occurrence of androgenic side effects.
CD002314	[ "14682413", "18430318", "11799368", "10398629", "8636828", "17140647", "16387583", "8703248", "20001651", "14512127", "9802368", "11549982", "12190656", "11368732", "8087329", "9105060", "7744189", "7359263", "2665584", "12113382", "12604023", "7638372", "10934090", "17418554", "16032934", "12503706", "9375539", "10335000", "12449158", "12969999", "17204725", "14716965", "18186995", "11112113", "9655717", "9864001", "2267922", "12590877", "20446755", "11422131", "16729788", "9713447", "12612295", "17983871", "17623754", "6958474", "8423275", "2188543" ]	[ "Comparative efficacy of once-daily therapy with inhaled corticosteroid, leukotriene antagonist or sustained-release theophylline in patients with mild persistent asthma.", "Role of regular treatment with inhaled corticosteroid or leukotriene receptor antagonist in mild intermittent asthma.", "Comparative efficacy and anti-inflammatory profile of once-daily therapy with leukotriene antagonist or low-dose inhaled corticosteroid in patients with mild persistent asthma.", "Randomised, placebo controlled trial of effect of a leukotriene receptor antagonist, montelukast, on tapering inhaled corticosteroids in asthmatic patients.", "Pilot study to assess the effect of inhaled corticosteroids on lung function in patients with cystic fibrosis.", "Long-term comparison of 3 controller regimens for mild-moderate persistent childhood asthma: the Pediatric Asthma Controller Trial.", "Response profiles to fluticasone and montelukast in mild-to-moderate persistent childhood asthma.", "Effect of inhaled corticosteroids on bronchial hyperresponsiveness in patients with mild asthma.", "Predicting short term response to anti-inflammatory therapy in young children with asthma.", "A randomized, double-blind, double-dummy, parallel-group, multicenter, dose-reduction trial of the minimal effective doses of budesonide and fluticasone dry-powder inhalers in adults with mild to moderate asthma.", "Effectiveness and safety of inhaled corticosteroids in controlling acute asthma attacks in children who were treated in the emergency department: a controlled comparative study with oral prednisolone.", "Comparison of inhaled salmeterol and oral zafirlukast in asthmatic patients using concomitant inhaled corticosteroids.", "Leukotriene receptor antagonist, montelukast, can reduce the need for inhaled steroid while maintaining the clinical stability of asthmatic patients.", "Long-acting beta2-agonist monotherapy vs continued therapy with inhaled corticosteroids in patients with persistent asthma: a randomized controlled trial.", "Endocrine and lung function in asthmatic children on inhaled corticosteroids.", "Leukotriene antagonist prevents exacerbation of asthma during reduction of high-dose inhaled corticosteroid. The Tokyo Joshi-Idai Asthma Research Group.", "High-dose and low-dose systemic corticosteroids are equally efficient in acute severe asthma.", "Corticosteroids in status asthmaticus.", "High doses of inhaled corticosteroids in unstable chronic asthma. A multicenter, double-blind, placebo-controlled study.", "Comparison of second controller medications in addition to inhaled corticosteroid in patients with moderate asthma.", "Zafirlukast versus budesonide on bronchial reactivity in subjects with mild-persistent asthma.", "Comparison of fluticasone propionate and sodium cromoglycate for the treatment of childhood asthma (an open parallel group study).", "Zafirlukast improves asthma control in patients receiving high-dose inhaled corticosteroids.", "Formoterol, montelukast, and budesonide in asthmatic children: effect on lung function and exhaled nitric oxide.", "Hydrofluoroalkane-134A beclomethasone or chlorofluorocarbon fluticasone: effect on small airways in poorly controlled asthma.", "Children with mild asthma: do they benefit from inhaled corticosteroids?", "Early parenteral corticosteroid administration in acute asthma.", "Randomised trial of an inhaled beta2 agonist, inhaled corticosteroid and their combination in the treatment of asthma.", "Dose reduction of inhaled corticosteroids under concomitant medication with montelukast in patients with asthma.", "A randomized controlled trial of inhaled flunisolide in the management of acute asthma in children.", "Smoking affects response to inhaled corticosteroids or leukotriene receptor antagonists in asthma.", "[A fixed combination of fluticasone and salmeterol permits better control of asthma than a beclomethasone dipropionate and montelukast combination].", "Poor adherence with inhaled corticosteroids for asthma: can using a single inhaler containing budesonide and formoterol help?", "Therapeutic ratio of inhaled corticosteroids in adult asthma. A dose-range comparison between fluticasone propionate and budesonide, measuring their effect on bronchial hyperresponsiveness and adrenal cortex function.", "Starting with a higher dose of inhaled corticosteroids in primary care asthma treatment.", "An inhaled steroid improves markers of airway inflammation in patients with mild asthma.", "Placebo controlled trial of systemic corticosteroids in acute childhood asthma.", "Effectiveness of montelukast versus budesonide on quality of life and bronchial reactivity in subjects with mild-persistent asthma.", "Cost effectiveness of leukotriene receptor antagonists versus long-acting beta-2 agonists as add-on therapy to inhaled corticosteroids for asthma: a pragmatic trial.", "Inhaled corticosteroids decrease vascularity of the bronchial mucosa in patients with asthma.", "Oral montelukast treatment of preschool-aged children with acute asthma.", "Randomised controlled trial of inhaled corticosteroids in patients with chronic obstructive pulmonary disease.", "Randomised controlled trial of montelukast plus inhaled budesonide versus double dose inhaled budesonide in adult patients with asthma.", "Comparative study of budesonide inhalation suspension and montelukast in young children with mild persistent asthma.", "Montelukast vs. inhaled low-dose budesonide as monotherapy in the treatment of mild persistent asthma: a randomized double blind controlled trial.", "Methodological aspects on clinical trials with inhaled corticosteroids: results of two comparisons between two steroid aerosols in patients with asthma.", "Treatment of allergic rhinitis with intranasal corticosteroids in patients with mild asthma: effect on lower airway responsiveness.", "Early administration of corticosteroids in emergency room treatment of acute asthma." ]	[ "The purpose of this study was to compare the efficacy and safety of the inhaled budesonide, sustained-release theophylline and montelukast, a leukotriene receptor antagonist, in patients with mild persistent asthma. In this single-center, randomized, parallel-group study that not designed blindly and placebo-controlled manner, 74 patients with mild persistent asthma were treated with either inhaled budesonide 400 microg once daily, oral montelukast 10 mg once daily, or sustained-release theophylline 400 mg once daily for 3 months. In all three treatment groups, improvements were attained in overall asthma control. Asthma symptom scores and supplemental beta2-agonist use were quite the same in all three treatment groups (P>0.05). Although inhaled budesonide group resulted in significantly greater improvements compared with the other two groups in the lung functions (P<0.05), the changes in FEV1 and PEF are within the baseline variability and there was no statistically significant difference among the groups when analyzed by treatment month (P>0.05). Exacerbations of asthma were experienced by 16% of the patients in the montekulast group, by 12.5% of the patients in the theophylline group, and by none of the patients in the budesonide group. The adverse event in each of the three groups was 12%, 16% and 16.7%, respectively. It is concluded that the most important clinical parameters do not point that one of the treatments is more effective than others. Treatment with inhaled corticosteroid is preferred, but sustained-release theophylline and leukotriene antagonists are alternative controller medications in mild persistent asthma.", "Current guidelines for asthma treatment do not recommend daily maintenance therapy in patients with mild intermittent (step 1) asthma. However, because there is increasing evidence that airway inflammation is present even in this patient group, maintenance anti-inflammatory therapy may be considered. We investigated the clinical impact of regular treatment with the inhaled corticosteroid beclomethasone dipropionate and the leukotriene receptor antagonist pranlukast in the patients concerned. The study was a randomized, controlled, parallel-group, multicenter trial. Eighty-five symptomatic patients with newly diagnosed mild intermittent asthma having normal pulmonary function were assigned beclomethasone or pranlukast for 8 weeks. Then, these medications were stopped for the next 16 weeks. Main outcome measures were asthma symptoms, pulmonary function, and airway inflammation. Treatment with beclomethasone and pranlukast significantly increased forced expiratory volume in 1 second and peak expiratory flow from baseline and decreased asthma symptom scores and sputum eosinophil counts and eosinophil cationic protein contents. After discontinuation of the treatment, symptom scores remained unchanged, but pulmonary function and airway inflammation were aggravated and then returned to the baseline levels. Therefore, maintenance therapy with inhaled corticosteroid or leukotriene receptor antagonist can provide further improvements in asthma symptoms, pulmonary function, and airway inflammation, and discontinuation of the therapy causes worsening of asthma, indicating that stopping or interrupting anti-inflammatory therapy may not be advisable in patients with symptomatic mild intermittent asthma.", "Current guidelines advocate the use of preventative anti-inflammatory therapy for mild persistent asthma.\n We compared the efficacy and anti-inflammatory profiles of a leukotriene receptor antagonist and a low dose of inhaled corticosteroid in patients with mild persistent asthma.\n Twenty-one adult patients with mild asthma received 4 weeks of either once-daily inhaled hydrofluoroalkane triamcinolone acetonide (450 microg/day ex-actuator dose) or oral montelukast (10 mg/day) in a randomized, placebo-controlled, single-blinded crossover study. Measurements were made before and after 2 and 4 weeks of each treatment.\n At the endpoint (after 4 weeks), triamcinolone and montelukast had improved the primary outcome (provocative dose of methacholine required to produce a 20% fall in FEV(1)) in comparison with placebo (P <.05), there being no difference between the treatments (1.09-fold; 95% CI 0.73 to 1.63). Triamcinolone was better than placebo or montelukast for effects on all other surrogate inflammatory markers (P <.05), including exhaled nitric oxide, blood eosinophils, serum eosinophil cationic protein, plasma intracellular circulating adhesion molecule 1, and plasma E-selectin. Both treatments improved (P <.05) morning and evening peak flow, nighttime beta2-agonist use, and symptoms in comparison with placebo, though triamcinolone was better than montelukast (P <.05) with regard to peak flow. Triamcinolone produced suppression (P <.05) of overnight urinary cortisol/creatinine and serum osteocalcin.\n Once-daily inhaled corticosteroid and leukotriene antagonist improved the primary outcome variable of bronchial hyperresponsiveness to a similar degree.", "To determine the ability of montelukast, a leukotriene receptor antagonist, to allow tapering of inhaled corticosteroids in clinically stable asthmatic patients.\n Double blind, randomised, placebo controlled, parallel group study. After a single blind placebo run in period, during which (at most) two inhaled corticosteroids dose decreases occurred, qualifying, clinically stable patients were allocated randomly to receive montelukast (10 mg tablet) or matching placebo once daily at bedtime for up to 12 weeks.\n 23 academic asthma centres in United States, Canada, and Europe.\n 226 clinically stable patients with chronic asthma receiving high doses of inhaled corticosteroids (113 randomised to montelukast and 113 to placebo).\n Every 2 weeks, the inhaled corticosteroids dose was tapered, maintained, or increased (rescue) based on a standardised clinical score.\n Last tolerated dose of inhaled corticosteroids.\n Compared with placebo, montelukast allowed significant (P=0. 046) reduction in the inhaled corticosteroid dose (montelukast 47% v placebo 30%; least square mean difference 17.6%, 95% confidence interval 0.3 to 34.8). Fewer patients on montelukast (18 (16%) v 34 (30%) placebo, P=0.01) required discontinuation because of failed rescue.\n Montelukast reduces the need for inhaled corticosteroids among patients requiring moderate to high doses of corticosteroid to maintain asthma control.", "To determine the effect of inhaled corticosteroids on lung function in patients with cystic fibrosis.\n We report a pilot study of 49 patients with cystic fibrosis and moderate to severe bronchial obstruction (forced expiratory volume in 1 second < or = 55% of the predicted value); 25 patients were given inhaled corticosteroids for 30 days (1500 micrograms of beclomethasone via spacer), and 24 patients had the same standard treatment but no inhaled corticosteroids.\n Forced vital capacity, forced expiratory volume in 1 second, and airway resistance showed significant improvement in both study groups, but thoracic gas volume and the diffusion capacity of the lung for carbon monoxide improved significantly only in the group given inhaled corticosteroids. When concomitant medications were taken into account, analysis of variance confirmed a significant effect of inhaled corticosteroids on the improvement of thoracic gas volume.\n Inhaled corticosteroids in combination with standard treatment can contribute to the improvement of lung function in patients with cystic fibrosis and moderate to severe bronchial obstruction. Our preliminary data seem encouraging enough to warrant a multicenter, long-term, blind control study.", "More evidence is needed on which to base recommendations for treatment of mild-moderate persistent asthma in school-aged children.\n The Pediatric Asthma Controller Trial (PACT) compared the effectiveness of 3 regimens in achieving asthma control.\n A total of 285 children (ages 6-14 years) with mild-moderate persistent asthma on the basis of symptoms, and with FEV(1) >or= 80% predicted and methacholine FEV(1) PC(20) <or= 12.5 mg/mL, were randomized to 1 of 3 double-blind 48-week treatments: fluticasone 100 microg twice daily (fluticasone monotherapy), fluticasone 100 microg/salmeterol 50 microg in the morning and salmeterol 50 mug in the evening (PACT combination), and montelukast 5 mg in the evening. Outcomes included asthma control days (primary outcome), exacerbations, humanistic measurements, and pulmonary function measurements.\n Fluticasone monotherapy and PACT combination were comparable in many patient-measured outcomes, including percent of asthma control days, but fluticasone monotherapy was superior for clinic-measured FEV(1)/forced vital capacity (P = .015), maximum bronchodilator response (P = .009), exhaled nitric oxide (P < .001), and PC(20) (P < .001). Fluticasone monotherapy was superior to montelukast for asthma control days (64.2% vs 52.5%; P = .004) and for all other control outcomes. Growth over 48 weeks was not statistically different (fluticasone, 5.3 cm; PACT combination, 5.3 cm; montelukast, 5.7 cm).\n Both fluticasone monotherapy and PACT combination achieved greater improvements in asthma control days than montelukast. However, fluticasone monotherapy was superior to PACT combination in achieving other dimensions of asthma control. Growth was similar in all groups.\n Therefore, of the regimens tested, the PACT study findings favor fluticasone monotherapy in treating children with mild-moderate persistent asthma with FEV(1) >or= 80% predicted, confirming current guideline recommendations.", "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.", "We studied the effect of inhaled budesonide on bronchial hyperresponsiveness (BHR) in twenty mild asthmatic patients. The study was conducted as a randomized, double-blind, placebo-controlled study. Before entering the study, the patients performed methacholine inhalation challenge (MIC) using a reservoir method to assess BHR. Then, they were randomly allocated to receive budesonide turbuhaler (200 micrograms/dose) or placebo turbuhaler two inhalations, twice daily for eight weeks. During the study, each patient recorded daily asthma score and daily number of puffs of beta 2 agonist and they were assessed at weeks 4 and 8. At the end of the treatment, MIC was repeated again. Patients receiving budesonide showed a significant improvement in airway responsiveness compared with those receiving placebo (p < 0.05). They also showed a significant improvement in asthma severity score and a significant decrease in beta 2 agonist bronchodilator use. This study also suggested that inhaled corticosteroids may be the primary treatment in patients, even with mild asthmatic and well-controlled symptoms.", "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.", "Inhaled corticosteroids are established first-line anti-inflammatory treatment for asthma. Clinical trials comparing inhaled corticosteroids must take into consideration that because of their excellent effect at low doses, they typically induce a near-maximal response in asthma patients.\n The aim of the present dose-response study was to estimate the minimal effective doses (MEDs) of budesonide and of fluticasone propionate via dry-powder inhaler in adults with mild to moderate asthma.\n This was a randomized, double-blind, double-dummy, parallel-group, multicenter, dose-reduction trial performed in adults to compare these 2 inhaled corticosteroids. After a 4- to 6-week run-in period with beclomethasone dipropionate 2000 pg/d, patients fulfilling defined criteria for asthma control were randomly allocated to treatment with budesonide or fluticasone, both administered BID at a total of 800 pg/d. At 5-week intervals, the dose was reduced to 400 and then 200 pg/d (200 and 100 pg BID) if asthma control was maintained according to further defined criteria. The MED was defined as the last dose level before deterioration of asthma control.\n Subjects were 197 asthmatic patients with a mean age of 40.6 years in the budesonide group and 41.5 years in the fluticasone group. In both groups, baseline mean forced expiratory volume in 1 second (FEV(1)) was 79.4% of the predicted normal volume and baseline mean FEV(1) reversibility was 22.3%. The median MED for both groups was 400 microg/d, with no detectable difference in dis-tributions. The budesonide-to-fluticasone ratio for the geometric mean MED was 123% (95% CI, 99-153 [not significant]). No statistically significant differences regarding lung function, symptom scores, or rescue medication usage were found between the treatment groups during the first treatment period. Adverse-event profiles were similar in both groups, and no unexpected adverse events were considered to be caused by the study drugs.\n This effect-controlled study did not detect a statistically significant difference between the MEDs for budesonide and fluticasone via dry-powder inhaler in adults with mild to moderate asthma.", "Inhaled corticosteroids have a greater antiinflammatory potency and fewer systemic effects than intravenous, intramuscular, or oral corticosteroids. However, their role in acute asthma has not been established. We prospectively investigated the efficacy and safety of inhaled corticosteroids in controlling moderately severe acute asthma attacks in children who were treated in the emergency department.\n Children who were treated in the emergency department with moderately severe asthma attacks after receiving treatment with inhaled terbutaline were allocated by double-blind design to receive 1 dose of either 1600 micro(g) budesonide turbohaler or 2 mg/kg prednisolone. The pulmonary index score and peak expiratory flow rate were measured hourly for the first 4 hours. After discharge the children were treated with the same initial doses given 4 times daily, followed by a 25% reduction in dose every second day for 1 week. Parents recorded asthma symptoms and use of beta-2 agonists on a daily diary card. Serum cortisol concentration was measured at the end of weeks 1 and 3.\n Twenty-two children (11 in each group) with similar baseline parameters completed the study. There was a similar improvement in pulmonary index score and peak expiratory flow rate in the 2 groups. Children treated with budesonide showed an earlier clinical response than those given prednisolone, who also showed a decrease in serum cortisol concentration.\n In children with moderately severe asthma attacks who were treated in the emergency department, a short-term dose schedule of inhaled budesonide turbohaler, starting with a high dose and followed by a decrease over 1 week, is at least as effective as oral prednisolone, without suppressing serum cortisol concentration.", "For asthmatic patients who remain symptomatic on inhaled corticosteroids, augmenting the therapy with additional long-term control medication is advocated. Long-acting beta2-adrenergic agonists and leukotriene modifiers are 2 therapeutic alternatives in the long-term controller class.\n To compare the addition of a long-acting beta2-adrenergic agonist to the addition of an oral leukotriene modifier for asthma therapy in patients who remain symptomatic on inhaled corticosteroids.\n Double-blind, double-dummy, parallel-group, multicenter clinical studies.\n 54 outpatient clinical centers.\n 429 male and female patients with asthma 12 years of age and older who were symptomatic while taking inhaled corticosteroids.\n Salmeterol xinafoate 42 mcg via metered dose inhaler twice daily or oral zafirlukast 20 mg twice daily.\n Pulmonary function, asthma symptoms, supplemental albuterol use, asthma quality of life scores, and adverse events.\n Inhaled salmeterol provided significantly greater improvement in pulmonary function as well as significantly greater relief of both daytime and nighttime asthma symptoms compared with oral zafirlukast in patients concurrently treated with inhaled corticosteroids. The use of supplemental albuterol was reduced to a greater extent with salmeterol compared with zafirlukast. Patients treated with salmeterol showed significantly greater improvement in Asthma Quality of Life Questionnaire (AQLQ) scores and were satisfied with how fast, how long, and how well the medication worked compared with patients in the zafirlukast group. Both treatments were well tolerated and demonstrated similar safety profiles.\n In patients with moderate to severe persistent asthma not sufficiently controlled with inhaled corticosteroids alone, the combination of inhaled salmeterol and inhaled corticosteroids is superior to the combination of oral zafirlukast and inhaled corticosteroids as stepwise therapy.", "Oral leukotriene receptor antagonists have been shown to have efficacy in chronic asthma.\n To determine whether the addition of montelukast could lead to a reduction in inhaled corticosteroid dose without a significant decrease in peak expiratory flow rate (PEFR).\n After a 4-week run-in period, 191 moderate-to-severe asthmatic patients whose asthma had been well controlled with daily inhaled corticosteroid therapy (beclometasone dipropionate 800 to 1600 micro g/day), were randomly assigned to one of two treatments - placebo (n = 98) or montelukast 10 mg once daily (n = 93) - for a 24-week, multicentre, double-blind, treatment period. At the beginning of the active treatment period, the daily dose of inhaled corticosteroid was halved in all of the patients. In addition, the inhaled corticosteroid dose was subsequently titrated every 8 weeks, based on PEFR, asthma symptoms and beta-agonist use.\n After 8 weeks of a 50% reduction in inhaled corticosteroid use, morning PEFR increased by 5.3 +/- 32.3 L/min from baseline in patients receiving montelukast and significantly decreased by 6.9 +/- 29.0 L/min in those receiving placebo (P = 0.035). In addition, evening PEFR significantly decreased by 9.8 +/- 28.5 L/min (P = 0.003) in the placebo group, but was maintained in the montelukast group. In spite of a subsequent 50% reduction in the inhaled corticosteroid dose every 8 weeks, morning and evening PEFRs were maintained over the 24-week treatment period in the montelukast group; PEFR significantly decreased in the placebo group. There was a significant difference between the two groups with regard to morning PEFR, therapy score and asthmatic score at weeks 8, 16 and 24, as well as evening PEFR at week 8. However, the symptom scores were not significantly different between the two groups or within each group.\n These data suggest that montelukast reduces the need for inhaled corticosteroids while maintaining asthma control over a 24-week period. Therefore, montelukast may be useful for long-term treatment in patients with asthma who require high doses of inhaled corticosteroids.", "Long-acting beta(2)-agonists are prescribed for patients with persistent asthma and are sometimes used without inhaled corticosteroids (ICSs). No evidence exists, however, to support their use as monotherapy in adults with persistent asthma.\n To examine the effectiveness of salmeterol xinafoate, a long-acting beta(2)-agonist, as replacement therapy in patients whose asthma is well controlled by low-dose triamcinolone acetonide, an ICS.\n A 28-week, randomized, blinded, placebo-controlled, parallel group trial conducted at 6 National Institutes of Health-sponsored, university-based ambulatory care centers from February 1997 to January 1999.\n One hundred sixty-four patients aged 12 through 65 years with persistent asthma that was well controlled during a 6-week run-in period of treatment with inhaled triamcinolone (400 microg twice per day).\n Patients were randomly assigned to continue triamcinolone therapy (400 microg twice per day; n = 54) or switch to salmeterol (42 microg twice per day; n = 54) or to placebo (n = 56) for 16 weeks, after which all patients received placebo for an additional 6-week run-out period.\n Change in morning and evening peak expiratory flow (PEF), forced expiratory volume in 1 second (FEV(1)), self-assessed asthma symptom scores, rescue albuterol use, asthma-specific quality-of-life scores, treatment failure, asthma exacerbation, bronchial reactivity, and markers of airway inflammation, compared among the 3 treatment groups.\n During the 16-week randomized treatment period, no significant differences between the salmeterol and triamcinolone groups were observed for conventional outcomes of clinical studies of asthma therapy-morning PEF, evening PEF, asthma symptom scores, rescue albuterol sulfate use, or quality of life. Both active treatments were superior to placebo. However, the salmeterol group had more treatment failures than the triamcinolone group (13/54 [24%] vs 3/54 [6%]; P =.004), as well as more asthma exacerbations (11/54 [20%] vs 4/54 [7%]; P =.04), greater increases in median (interquartile range) sputum eosinophils (2.4% [0.0% to 10.6%] vs -0.1% [-0.7% to 0.3%]; P<.001), eosinophil cationic protein (71 [-2 to 430] U/L vs -4 [-31 to 56] U/L; P =.005), and tryptase (3.1 [2.1 to 7.6] ng/mL vs 0.0 [0.0 to 0.7] ng/mL; P<.001). The duration of benefit when patients were switched from active treatment to placebo after 22 weeks of randomized treatment was not significantly longer in the triamcinolone group than in the salmeterol group.\n Patients with persistent asthma well controlled by low doses of triamcinolone cannot be switched to salmeterol monotherapy without risk of clinically significant loss of asthma control.", "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.", "To test whether the leukotriene antagonist ONO-1078 (pranlukast) prevents asthma exacerbations during reduction of high-dose inhaled corticosteroid, we conducted a randomized, double-blind, placebo-controlled study in 79 asthma patients requiring high doses (1,500 microg/d or more) of inhaled beclomethasone dipropionate (BDI) for clinical control (duration of asthma, 11.0 +/- 3.1 yr; duration of BDI treatment, 0.5 +/- 0.3 yr; FEV1 percentage of predicted, 80.7 +/- 2.0%). After a 2-wk run-in period, the doses of BDI were halved, while the patients were assigned to receive orally ONO-1078, 450 mg twice daily, or placebo. In the placebo group FEV1 decreased by 0.33 +/- 0.20 L after 6 wk (p < 0.001). Likewise, morning and evening PEF decreased by 46 +/- 7 L/min and 18 +/- 6 L/min, respectively. By contrast these variables were sustained above baseline in the ONO-1078 group. The number of daytime and nighttime asthma symptoms and the use of beta2-agonist increased in the placebo group, whereas they remained unchanged in the ONO-1078 group. In the placebo group concentrations of serum eosinophil cationic protein and exhaled nitric oxide increased (p = 0.007 and p = 0.025, respectively), compared with no change in the ONO-1078 group. Therefore, the leukotriene antagonist ONO-1078 prevents the asthma deterioration provoked by a 6-wk reduction of the dose of inhaled BDI into half.", "The optimal amount of systemic corticosteroids to be used in acute severe asthma remains an unresolved issue. In this double-blind, randomized study we compared two doses of methylprednisolone (1 vs 6 mg.kg-1 q.d.) in asthmatics presenting with an acute severe asthma attack, unresponsive to an intensive beta 2-agonist regimen administered during a run-in period. Concurrent therapy, including oxygen, inhaled and intravenous salbutamol, and aminophylline was strictly standardized. The response was assessed by serial bedside spirometry. The primary outcome measurement was forced expiratory volume in one second (FEV1) (expressed as percentage of predicted values) at 24 and 44 h. The trial was designed in order to achieve a statistical power of 90%. Twenty three patients were included in the low-dose group and 24 in the high-dose group. Both groups were comparable in terms of demographic profiles, history of asthma, and severity of the current attack. Improvement in pulmonary function was similar in both groups. At 44 h, the mean (+/- SD) FEV1 values were 53 +/- 22 and 45 +/- 14% in the low and in the high-dose group respectively (NS). We conclude that high dose systemic corticosteroids offer no further benefit over low-doses in the treatment of severe acute asthma.", "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.", "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 objective of this study was to compare the efficacy and safety of the second controller medications (long-acting beta2-agonist, leukotriene receptor antagonist and sustained-release theophylline) used in addition to inhaler corticosteroid treatment in moderate persistent asthma. A total of 64 patients with asthma, in the moderate persistent asthma category, were divided into three groups. Patients, all of whom were concurrently using inhaled corticosteroid (Budesonide 400 microg twice daily), were treated for 3 months with either inhaled formoterol 9 microg twice daily (first group), oral zafirlukast 20 mg twice daily (second group), or sustained-release theophylline 400 mg once daily (third group). All of the patients were subjected to assessments on the subject of peak expiratory flow (PEF) variability, forced expiratory volume in 1 sec (FEV1), asthma symptom scores (daytime and night-time), supplemental terbutalin use, asthma exacerbations and adverse events. Over the 3-month treatment period. In all of the three groups, significant improvements were recorded in the lung function, asthma symptom scores and supplemental terbutalin use criteria, as a result oftreatments applied. Formoterol treatment resulted in significantly greater and earlier improvements compared with the other two groups in several criteria: PEF variability (17.9 +/- 2.5; 21.9 +/- 3.2; 23.7 +/- 3.3; P < 0.001); asthma symptom score (daytime) (1.6 +/- 0.5; 1 +/- 0.5; 2.0 +/- 0,5; P < 0.05); asthma symptom score (night-time) (1.2 +/- 0.4; 2.2 +/- 0.5; 16 +/- 0.6; P < 0001); and supplement alter butalin use (1.2 +/- 0.3; 1.8 +/- 0.5; 1.7 +/- 0.5; P < 0.05). However, at the end of the treatment, in all of the three groups studied, improvements were attained in overall asthma control and there was no statistical difference among the groups. Although there were no side effects which required the discontinuation of the treatment, it was observed that the maximum side effect was in the second group (20%, 31.6% and 20%, respectively). In conclusion, in patients who still have symptoms on treatment with inhaled corticosteroids, the addition of a long-acting beta2-agonist, leukotriene antagonists or sustained-release theophylline to the treatment is a logical approach, and, in addition to inhaled corticosteroids, any one of these second controller medications may be chosen in patients with moderate asthma.", "Asthma is one of the most common chronic diseases in children and adults. Recent studies have shown that in asthmatic patients treated with inhaled corticosteroids there is a better diseases control when adding a second drug, than increasing the corticosteroids dose. The aim of this study has been to evaluate the effectiveness and tolerance of zafirlukast, a leukotriene receptor antagonist, versus budesonide in clinically steady patients with mild persistent bronchial asthma. We have enrolled 36 subjects non smokers, with mild persistent bronchial asthma and 12 healthy subjects as control group. At the beginning of this study and at the end of the treatment (8 weeks), all patients underwent complete clinical work-up, pulmonary function testing (FEV1, PEF and FVC) and methacholine challenge test. The patients were divided into 3 groups: group A) 20 mg of zafirlukast twice a day; group B) 400 mg of budesonide twice a day; group C) 20 mg of zafirlukast twice a day and 400 mg of budesonide twice a day. Basal FEV1 and PEF presented no significant statistical differences between control subjects and patients of group A, B and C. After eight weeks there were no significant changes for FEV1 and PEF among the three groups. After therapy a strong significant increase of PD20 was documented in group A (p<0.005), group B (p<0.001) and group C (p<0.005), respect to baseline values. The antileukotriene drugs could be taken as an alternative drug, or in association with low-dose inhaled corticosteroids, in patients with mild persistent asthma, both for their clinical effectiveness and their easy ingestion, which is confirmed in compliance studies on inhaled steroids.", "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.", "Not all asthma can be adequately controlled, despite the use of high-dose inhaled corticosteroids. Because cysteinyl-leukotrienes (Cys-LT) have been implicated in the pathogenesis of asthma, we hypothesized that the leukotriene receptor antagonist zafirlukast, in combination with high-doses of inhaled corticosteroids, might be efficacious in severe asthma. In a double-blind, parallel group study, 368 chronic adult asthmatic patients treated with inhaled corticosteroids (1,000 to 4,000 microgram/d), who had a predefined level of asthma symptoms during the run in period of the study, were randomly assigned to receive additional treatment with a high dose of zafirlukast (80 mg twice daily) (n = 180) or placebo (n = 188) for 6 wk. Compared with placebo, zafirlukast produced a significant improvement over baseline in the primary study endpoint of mean morning peak expiratory flow rate (PEFR) (18.7 L/min versus 1.5 L/min, p < 0.001), as well as in evening PEFR (p < 0.01), FEV(1) (p < 0.05), daytime symptom score (p < 0.001), and beta(2)-agonist use (p < 0.001). Furthermore, zafirlukast significantly reduced the risk of an exacerbation of asthma (odds ratio [OR]: 0.61; 95% confidence interval [CI]: 0.38 to 0.99) and the risk of patients requiring a further increase in asthma controller therapy (OR: 0.4; 95% CI: 0.2 to 0.8). In conclusion, in patients taking high-dose inhaled corticosteroids, zafirlukast improves pulmonary function and asthma symptoms, and reduces the risk of an asthma exacerbation, suggesting that the contribution of leukotrienes to asthma symptoms and exacerbations is not adequately controlled by high-dose inhaled corticosteroids.", "It has been proposed that asthma control may be achieved in part by minimizing airway inflammation. The simultaneous effects of inhaled steroids associated with long-acting beta-agonists and leukotriene antagonists on pulmonary function and airway inflammation are still largely unexplored in children with moderate persistent asthma.\n The aim of this study was to investigate the effects of add-on therapy with long-acting beta-agonists and leukotriene antagonists on FEV1 and exhaled nitric oxide levels (FENO) in children.\n Forty-eight steroid-naïve atopic asthmatic children, 7-11 years of age, were randomly treated in four groups for two consecutive one-month periods, as follows: (1) first month: budesonide 200 microg twice daily; second month: budesonide 400 microg twice daily; (2) first month: budesonide 200 microg twice daily+formoterol 9 microg twice daily; second month: budesonide 200 microg twice daily+montelukast 5mg once daily; (3) first month: budesonide 200 microg twice daily+montelukast 5mg once daily; second month budesonide 200 microg+formoterol 9 microg twice daily; (4) first and second month: budesonide 400 microg twice daily.\n All treatments resulted in a significant increase in lung function and a decrease in FENO compared with values at baseline. Budesonide+montelukast in combination was the most effective treatment for reducing FENO levels.\n This study demonstrates that add-on therapy with montelukast plus low-dose budesonide is more effective than the addition of long-acting beta-agonists or doubling the dose of budesonide for controlling FENO in asthmatic children.", "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.", "In children with mild asthma, who show hardly any abnormalities in pulmonary function, objective measurement of the effect of inhaled corticosteroids is difficult. The short term effect of fluticasone propionate (FP) in these children was evaluated, using both subjective and objective parameters. A total of 68 children (5-10 yrs old) were randomly assigned to either FP 250 microg or placebo twice daily as metered-dose inhaler via spacer during 12 weeks. Symptom scores, use of rescue medication, wheezing, parent global evaluation and pulmonary function tests including forced expiratory volume in one second (FEV1), peak expiratory flow (PEF) and bronchial responsiveness (provocation dose of methacholine causing a 20% fall in FEV1 (PD20)) were evaluated. FP-treated versus placebo-treated children showed significant changes in percentage symptom-free days, use of beta2-mimetics, morning and evening PEF, FEV1 % pred and wheezing. No significant improvements were found in parent global evaluation, absolute values of FEV1 nor PD20. These findings show that inhaled corticosteroids are effective in children with mild asthma. This effect can be assessed by both objective and subjective parameters. Early start of inhaled corticosteroids should be considered even when pulmonary function is normal.", "To test the hypothesis that early parenteral corticosteroid administration may be associated with a rapid improvement in airflow obstruction in adult asthmatic patients, a randomized, double-blind placebo-controlled study was carried out. Forty-five adult asthmatic patients, with initial peak expiratory flow rates (PEFRs) of < 200 L/sec received an intravenous bolus of either 125 mg methylprednisolone (MP) or normal saline before any other emergency department treatments. This was immediately followed by 3 aerosol treatments of 2.5 mg of albuterol separated by 20-minute intervals. PEFRs and heart rates were measured over a 1-hour time frame. There was not a significantly higher rate of increase of PEFR in the MP group compared with the saline group. Similarly, the rate of increase in percent PEFR showed a trend to being higher in the saline group (P = .061). There was no significant difference in the proportion of hospitalizations and side effects between the two groups. Adjustment for other variables did not result in a model showing an enhanced PEFR improvement with MP treatment. This study does not support the concept that corticosteroid treatment effects are beneficial within the first hour after administration. Further studies of rapid-acting modalities to enhance bronchodilation are needed in treating acute asthmatics.", "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.", "The present study aimed at comparing the effects of a dose reduction of inhaled corticosteroids on lung function, indirect measures of airway inflammation and clinical scores during treatment with a leucotriene receptor antagonist. In 50 patients (mean forced expiratory volume in one second (FEV1) 94% predicted), steroid doses (800 microg beclomethasone dipropionate) were first reduced to 50% and then to 25%, for 6 weeks each. One group received a placebo and the other group received montelukast (10 mg). The first reduction did not cause significant effects. During the second, FEV1 and peak expiratory flow decreased in both groups (p<0.001). Daytime symptoms were not altered with placebo but were reduced by montelukast (p<0.05). Night-time symptoms were slightly elevated with placebo (p<0.05) but not montelukast, as well as the use of supplemental salbutamol. Changes in provocative concentration of methacholine causing a 20% fall in FEV1 (PC20), sputum eosinophils and exhaled nitric oxide were mostly nonsignificant for both placebo and montelukast. These data demonstrate that a 75% reduction in the dose of steroid given to patients with asthma led to a deterioration in lung function not prevented by montelukast, whereas changes in clinical state seemed to favour montelukast treatment. It therefore appears that potential effects of montelukast, in the presence of low-dose steroids, could not be attributed to single indices of lung function or airway inflammation.", "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.", "One-quarter to one-third of individuals with asthma smoke, which may affect response to therapy and contribute to poor asthma control.\n To determine if the response to an inhaled corticosteroid or a leukotriene receptor antagonist is attenuated in individuals with asthma who smoke.\n In a multicenter, placebo-controlled, double-blind, double-dummy, crossover trial, 44 nonsmokers and 39 light smokers with mild asthma were assigned randomly to treatment twice daily with inhaled beclomethasone and once daily with oral montelukast.\n Primary outcome was change in prebronchodilator FEV(1) in smokers versus nonsmokers. Secondary outcomes included peak flow, PC(20) methacholine, symptoms, quality of life, and markers of airway inflammation. Despite similar FEV(1), bronchodilator response, and sensitivity to methacholine at baseline, subjects with asthma who smoked had significantly more symptoms, worse quality of life, and lower daily peak flow than nonsmokers. Adherence to therapy did not differ significantly between smokers and nonsmokers, or between treatment arms. Beclomethasone significantly reduced sputum eosinophils and eosinophil cationic protein (ECP) in both smokers and nonsmokers, but increased FEV(1) (170 ml, p = 0.0003) only in nonsmokers. Montelukast significantly increased a.m. peak flow in smokers (12.6 L/min, p = 0.002), but not in nonsmokers.\n In subjects with mild asthma who smoke, the response to inhaled corticosteroids is attenuated, suggesting that adjustments to standard therapy may be required to attain asthma control. The greater improvement seen in some outcomes in smokers treated with montelukast suggests that leukotrienes may be important in this setting. Larger prospective studies are required to determine whether leukotriene modifiers can be recommended for managing asthma in patients who smoke.", "It is now recommended to add an inhaled long-acting beta 2-agonist, or as an alternative, to add a leukotriene-antagonist, in patients whose asthma is insufficiently controlled with an inhaled corticosteroid alone. A randomised, multicentre, open-label, parallel-group study was carried out in 246 patients of at least 15 years, whose asthma was not adequately controlled with a medium dose of an inhaled corticosteroid. They received either fluticasone/salmeterol combination 250/50 micrograms one inhalation twice daily or CFC beclomethasone dipropionate 250 micrograms two puffs twice daily plus montelukast 10 mg in the evening for 12 weeks. The mean morning PEFR (main criterion) was significantly (p = 0.017) more improved with fluticasone/salmeterol (+44.2 L/min) than with beclomethasone dipropionate plus montelukast (+31.0 L/min). Other outcomes showed significantly better improvements (p 0.022 Pound) with fluticasone/salmeterol than with beclomethasone plus montelukast. The two treatments were well tolerated. Fluticasone/salmeterol provided a better asthma control than beclomethasone dipropionate plus montelukast in patients insufficiently controlled with an inhaled corticosteroid alone.", "Poor adherence with inhaled corticosteroids is an important problem in asthma management. Previous approaches to improving adherence have had limited success.\n To determine whether treatment with a single inhaler containing a long-acting beta(2)-agonist and a corticosteroid for maintenance treatment and symptom relief can overcome the problem of poor adherence with inhaled corticosteroids.\n Randomised, parallel group, open-label trial.\n Forty-four general practices in Nottinghamshire.\n Participants who used less than 70% of their prescribed dose of inhaled corticosteroid and had poorly controlled asthma were randomised to budesonide 200 microg one puff twice daily plus their own short-acting beta(2)-agonist as required (control group), or budesonide/formoterol 200/6 microg one puff once daily and as required (active group) for 6 months. The primary outcome was inhaled corticosteroid dose.\n Seventy-one participants (35 control, 36 active group) were randomised. Adherence with budesonide in the control group was approximately 60% of the prescribed dose. Participants in the active group used approximately 80% more budesonide than participants in the control group (448 versus 252 microg/day, mean difference 196 mug, 95% confidence interval 113 to 279; P<0.001) and were less likely to withdraw from the study (3 versus 13; P<0.01). No safety issues were identified.\n Using a single inhaler for both maintenance treatment and symptom relief approximately doubled the dose of inhaled corticosteroid taken, suggesting this could be a useful strategy to overcome the problems related to poor adherence with inhaled corticosteroids.", "Inhaled corticosteroids have become the mainstay treatment of bronchial asthma. However, simultaneous evaluations of efficacy and side effects are few. This study aimed to compare the relative effect of fluticasone propionate (FP) and budesonide (BUD) on bronchial responsiveness and endogenous cortisol secretion in adults with asthma. The study was double-blind and included 66 adults with asthma, who were randomized to FP (n = 33) or BUD (n = 33). Prestudy, all participants were clinically stable, using inhaled corticosteroids and hyperresponsive to methacholine. Eligible patients were randomized to three consecutive 2-wk periods with either FP 250 microg twice daily, FP 500 microg twice daily, and FP 1,000 microg twice daily, or BUD 400 microg twice daily, BUD 800 microg twice daily, and BUD 1,600 microg twice daily, delivered by Diskhaler and Turbuhaler, respectively. Before randomization and at the end of each treatment, bronchial methacholine PD(20), 24-h urinary cortisol excretion (24-h UC), plasma cortisol, serum osteocalcin, and blood eosinophils were determined. The relative PD(20) potency between FP and BUD was 2.51 (95% CI, 1.05-5.99; p < 0. 05), while the relative 24-h UC potency was 0.60 (95% CI, 0.44-0.83; p < 0.01). The differential therapeutic ratio (FP/BUD) based on PD(20) potency and 24-h UC was 4.18 (95% CI, 1.16-15.03; p < 0.05). The difference in systemic potency was also seen for plasma cortisol, serum osteocalcin, and blood eosinophils. Therapeutic ratio over a wide dose range, determined by impact on bronchial responsiveness and endogenous corticosteroid production, seems to favor FP.", "New British guidelines on the treatment of asthma (9) advocate starting with a higher dose of inhaled corticosteroids in newly detected asthma patients. We investigated whether initiating inhaled steroid treatment with a higher dose is clinically more effective than a lower dose in steroid naive patients with asthma. The study had a 13-wk randomized, double-blind, parallel design: 1-mo treatment with 400 microg budesonide twice a day, or 100 microg budesonide twice a day by dry powder inhaler, and follow-up treatment period of 2 mo with 200 microg budesonide once daily for all patients. Forty patients started with 400 microg budesonide twice daily, 44 with 100 microg budesonide twice daily. Mean age was 32 yr, baseline FEV1 value 84% predicted, reversibility 9% from baseline, and mean bronchodilator use 1.6 inhalations/d in the run-in period. After 4 wk of treatment with 400 microg and 100 microg budesonide twice daily mean morning peak expiratory flow (PEF) increased 27 L/min (SD 50), and 38 L/ min (SD 53), respectively (p = 0.30); mean symptom score improved from 1.1 to 0.6 and from 1.1 to 0.5. These effects were maintained in the 2 mo follow-up. This study suggests that starting inhaled corticosteroids at a higher dose is not superior to a lower dose in the treatment of newly detected asthma.", "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.", "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.", "Insufficient data exist to evaluate the comparative effects of inhaled corticosteroids (ICS) versus leukotriene receptor antagonist (LTRA) on airway inflammation and quality of life (QoL). The aim of the study was to compare the effectiveness of montelukast compared to budesonide at different doses on QoL and bronchial reactivity in mild-asthmatic adult patients. 45 subjects with bronchial asthma were randomly assigned to a different treatment and divided in 3 treatment groups: A: 400 mg of budesonide twice a day; B: 10 mg of montelukast daily; C: 10 mg of montelukast daily plus 400 mg of budesonide twice a day. At the beginning of the study and at the end of the treatment period (16 weeks) all patients underwent complete clinical evaluation, pulmonary function testing and methacholine challenge test (MCHt). In group A the increase from baseline was 153.4&#x0025;, in group C was 133.2&#x0025;, and in group B 247.7&#x0025;, the latter increase being statistically significant compared to that in the other 2 groups (p&#x003C; 0.005 Wilcoxon test). In all domains the improvement in quality of life in the group treated with montelukast (group B) was significantly greater than that in the group treated with both medications (group C): in particular, the improvement was consistent in the symptoms (p&#x003C; 0.01) and emotions (p&#x003C; 0.01) domains, and weaker in the physical activity (p&#x003C; 0.05). A similar difference was observed between group B and A, but only in the symptoms (p&#x003C;0.01), emotions (p&#x003C;0.01), and environmental stimuli domains (p&#x003C;0.05). The personal perception of their own disease is important for a correct therapeutic management of asthma. In order to optimize the treatment, a complete adherence of the patient to the treatment itself is required, to be achieved through simplification of therapeutic schedule and easy administration of medications. Montelukast may be considered a valid alternative in the treatment of mild-persistent asthma, both for the clinical and functional benefits and for the great advantage of the once-daily dosage, which consistently improves the compliance with the chronic treatment of the disease.", "Information is lacking on the relative effectiveness and cost effectiveness--in a real-life primary-care setting--of leukotriene receptor antagonists (LTRAs) and long-acting beta2 adrenergic receptor agonists (beta2 agonists) as add-on therapy for patients whose asthma symptoms are not controlled on low-dose inhaled corticosteroids (ICS).\n To estimate the cost effectiveness of LTRAs compared with long-acting beta2 agonists as add-on therapy for patients whose asthma symptoms are not controlled on low-dose ICS.\n An economic evaluation was conducted alongside a 2-year, pragmatic, randomized controlled trial set in 53 primary-care practices in the UK. Patients aged 12-80 years with asthma insufficiently controlled with ICS (n = 361) were randomly assigned to add-on LTRAs (n = 176) or long-acting beta2 agonists (n = 185). The main outcome measures were the incremental cost per point improvement in the Mini Asthma Quality of Life Questionnaire (MiniAQLQ), per point improvement in the Asthma Control Questionnaire (ACQ) and per QALY gained from perspectives of the UK NHS and society.\n Over 2 years, the societal cost per patient receiving LTRAs was pounds sterling 1157 versus pounds sterling 952 for long-acting beta2 agonists, a (significant, adjusted) increase of pounds sterling 214 (95% CI 2, 411) [year 2005 values]. Patients receiving LTRAs experienced a non-significant incremental gain of 0.009 QALYs (95% CI -0.077, 0.103). The incremental cost per QALY gained from the societal (NHS) perspective was pounds sterling 22,589 (pounds sterling 11,919). Uncertainty around this point estimate suggested that, given a maximum willingness to pay of pounds sterling 30,000 per QALY gained, the probability that LTRAs are a cost-effective alternative to long-acting beta2 agonists as add-on therapy was approximately 52% from both societal and NHS perspectives.\n On balance, these results marginally favour the repositioning of LTRAs as a cost-effective alternative to long-acting beta2 agonists as add-on therapy to ICS for asthma. However, there is much uncertainty surrounding the incremental cost effectiveness because of similarity of clinical benefit and broad confidence intervals for differences in healthcare costs.\n UK National Research Register N0547145240; Controlled Clinical Trials ISRCTN99132811.", "Increased vascularity in airway mucosa is a distinctive feature of airway remodelling in asthma. While corticosteroids have proved most effective in modifying airway inflammation, the effect of inhaled corticosteroids on increased airway mucosal vascularity in asthmatics has been little studied.\n We examined the effect of inhaled corticosteroid on airway vascularity in bronchial biopsy specimens taken from asthmatic patients.\n We studied bronchial biopsies from 28 asthmatic patients before and after treatment with inhaled beclomethasone dipropionate (BDP) 800 microg/daily, or placebo, for 6 months in a double-blind manner. Biopsy specimens were evaluated for number of vessels and percentage of area occupied by vessels, using computerized image analysis after staining for type IV collagen in vessel walls. Specimens were also examined for extent of collagen III in the subepithelial basement membrane. In addition, we compared asthmatic specimens with biopsy specimens taken from non-asthmatic control subjects.\n There was a significant increase in number of vessels (P < 0.01) and percent vascularity (P < 0.001) in the submucosa of asthmatic patients compared with control subjects. After 6 months of treatment, we observed significant improvements in forced expiratory volume in 1 s (FEV1), FEV1% and airway responsiveness (P < 0.05, each) in the BDP treatment group compared with the placebo group. This was accompanied by significant decreases in both vessel number and percent vascularity in the airways of BDP-treated patients (P < 0.05, each). We also observed a significant correlation between change in percent vascularity and change in collagen III thickness in the BDP-treated patients (rs = 0.90, P < 0.001). Furthermore, the change in percent vascularity was inversely correlated with both FEV1 (rs = -0.49, P < 0.05) and airway responsiveness (rs = -0.36, P < 0.05).\n These findings suggest that inhaled corticosteroid treatment of asthma reduced airway wall vascularity during airway remodelling.", "Increased amounts of cysteinyl leukotrienes have been demonstrated in urine samples from asthmatic patients, particularly during exacerbations of asthma. Although the use of leukotriene receptor antagonists has been recommended in the treatment of chronic asthma, no guidelines are available regarding their use in the treatment of acute asthma.\n To investigate the safety and effectiveness of a 4-mg tablet of oral montelukast in addition to short-acting beta2-agonist bronchodilator as the initial treatment in mild to moderate asthma exacerbations in children between 2 and 5 years old.\n Fifty-one patients who were experiencing mild to moderate asthma exacerbation were included in a randomized, double-blind, placebo-controlled, parallel-group study. Each patient received either a 4-mg tablet of montelukast or placebo in addition to inhaled salbutamol and were followed up for 4 hours. The pulmonary index score, respiratory rate, and pulse were determined at baseline and throughout 4 hours after administration.\n Compared with placebo, the pulmonary index scores and respiratory rates were significantly lower in the montelukast group starting at 90 minutes (P = .01). This difference persisted at 120, 180, and 240 minutes of the study (P = .008, P = .02, and P = .048, respectively). At the end of the first hour of treatment, oral steroid need was 20.8% and 38.5% in patients randomized to the montelukast and placebo groups, respectively (P = .22). Hospitalization rates were not different between the 2 treatment groups.\n A single 4-mg tablet of montelukast had the potential to provide additive clinical benefit in mild to moderate acute asthma in preschool-aged children when administered concomitantly with short-acting beta2-agonist bronchodilators as the initial treatment.", "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.", "Inhaled corticosteroids (ICS) affect many inflammatory pathways in asthma but have little impact on cysteinyl leukotrienes. This may partly explain persistent airway inflammation during chronic ICS treatment and failure to achieve adequate asthma control in some patients. This double blind, randomised, parallel group, non-inferiority, multicentre 16 week study compared the clinical benefits of adding montelukast to budesonide with doubling the budesonide dose in adults with asthma.\n After a 1 month single blind run in period, patients inadequately controlled on inhaled budesonide (800 microg/day) were randomised to receive montelukast 10 mg + inhaled budesonide 800 microg/day (n=448) or budesonide 1600 microg/day (n=441) for 12 weeks.\n Both groups showed progressive improvement in several measures of asthma control compared with baseline. Mean morning peak expiratory flow (AM PEF) improved similarly in the last 10 weeks of treatment compared with baseline in both the montelukast + budesonide group and in the double dose budesonide group (33.5 v 30.1 l/min). During days 1-3 after start of treatment, the change in AM PEF from baseline was significantly greater in the montelukast + budesonide group than in the double dose budesonide group (20.1 v 9.6 l/min, p<0.001), indicating faster onset of action in the montelukast group. Both groups showed similar improvements with respect to \"as needed\" beta agonist use, mean daytime symptom score, nocturnal awakenings, exacerbations, asthma free days, peripheral eosinophil counts, and asthma specific quality of life. Both montelukast + budesonide and double dose budesonide were generally well tolerated.\n The addition of montelukast to inhaled budesonide is an effective and well tolerated alternative to doubling the dose of inhaled budesonide in adult asthma patients experiencing symptoms and inadequate control on budesonide alone.", "Budesonide inhalation suspension and the leukotriene receptor antagonist montelukast have demonstrated efficacy in children with mild persistent asthma, but comparative long-term studies in young children are needed.\n To compare the long-term efficacy and safety of budesonide inhalation suspension and montelukast.\n After a run-in period, children 2 to 8 years old with mild asthma or recurrent wheezing were randomized to once-daily budesonide inhalation suspension 0.5 mg or once-daily oral montelukast 4 or 5 mg for 52 weeks. Subjects were stepped up to twice-daily budesonide inhalation suspension or oral corticosteroids for mild or severe asthma worsening, respectively. The primary outcome was time to first additional medication for asthma worsening at 52 weeks. Secondary variables included times to the first additional asthma medication measured at 12 and 26 weeks; times to the first asthma exacerbation (mild and severe) measured at 12, 26, and 52 weeks; exacerbation rates (mild and severe) over a period of 52 weeks; diary variables (eg, peak expiratory flow [PEF]); patient-reported outcomes; and Global Physician and Caregiver Assessments.\n No significant between-group differences were observed for time to first additional asthma medication at 52 weeks; however, time to first additional asthma medication was longer (unadjusted P = .050) at 12 weeks and exacerbation rates were lower over a period of 52 weeks (unadjusted P = .034) for budesonide versus montelukast. Time to first severe exacerbation (requiring oral corticosteroids) was similar in both groups, but the percentage of subjects requiring oral corticosteroids over a period of 52 weeks was lower with budesonide (25.5% vs 32.0%). Peak flow and Caregiver and Physician Global Assessments favored budesonide.\n Both treatments provided acceptable asthma control; however, overall measures favored budesonide inhalation suspension over montelukast.\n These findings are consistent with studies in older children demonstrating better outcomes with inhaled corticosteroids versus montelukast.", "Guidelines recommend daily controller therapy for mild persistent asthma. Montelukast has demonstrated consistent benefit in controlling symptoms of asthma and may be an alternative, orally administered, nonsteroidal agent for treating mild asthma. Aim: To determine whether montelukast is as effective as budesonide in controlling mild persistent asthma as determined by FEV(1).\n Between November 2003 to October 2005, participants aged 5-15 years with recently diagnosed mild persistent asthma (n = 62) were randomized to oral montelukast (5 mg daily) [N(1) = 30] or inhaled budesonide (400 microg per day in two doses) [N(2) = 32] in a single center, double-blind study.\n Baseline demographic and spirometric parameters were comparable. The median (95% confidence interval) percentage predicted FEV(1) was similar in the two groups after 12 weeks of treatment (budesonide: 76.70 (67.96-90.53%), montelukast: 75 (67.40-88.47)%; p = 0.44). There was similar improvement in spirometric parameters and clinical symptom scores in both the groups. There was no statistically significant difference between the groups in the need for rescue drugs as well as side effects reported by parents.\n Montelukast is as effective as inhaled budesonide in the treatment of mild persistent asthma in children aged 5-15 years. Montelukast may be used as an alternative to low dose inhaled corticosteroids for management of mild persistent asthma.", "The efficacy of beclomethasone dipropionate aerosol (BDA) 100 micrograms q.i.d. was compared with that of budesonide aerosol 10 micrograms q.i.d. in 17 patients. The efficacy of inhaled BDA 100 micrograms q.i.d. was also compared with that of budesonide 50 micrograms q.i.d. with and without an extension tube (Inhalet) attached to the actuator in 23 patients. Both studies included placebo periods. The trials were performed with the cross-over technique in patients with stable asthma. Each treatment was randomized and given in periods of two weeks starting with a run-in period. The patients recorded peak expiratory flow rates (PEF) twice daily and filled in diary cards for cough, wheeze, breathing difficulties and use of beta 2-receptor stimulant aerosol. In the first study the patients came to the hospital twice weekly throughout the trial for spirometry and interview. In the second study they came every second week. Budesonide and BDA were superior to placebo. Budesonide in doses of 100 micrograms and 50 micrograms were as efficacious as BDA 100 micrograms q.i.d., while budesonide 50 micrograms q.i.d. with Inhalet was slightly more effective. Treatment for two weeks was found to be sufficient. For each parameter the average of the last four days of each period was found to be relevant in the comparison. The placebo period should preferably not be placed at random in the trial, but as the last treatment period.", "The effect of treatment of allergic rhinitis with intranasal corticosteroids on lower airway responsiveness was assessed in a randomized, double-blind, placebo-controlled, crossover study. Twenty-one young patients with perennial allergic rhinitis and asthma, with documented lower airway hyperresponsiveness (PC20 methacholine < 8 mg/ml), were treated with intranasal aqueous beclomethasone dipropionate and placebo, each given for 4 weeks. Patients recorded rhinitis and asthma symptom scores and monitored peak expiratory flow rates every morning and evening. Patients recorded global assessment of rhinitis and global asthma symptom scores at the beginning and end of each treatment. PC20 methacholine was performed at baseline and at the end of each treatment period. Intranasal beclomethasone dipropionate significantly reduced global rhinitis symptom scores (p = 0.05) after 4 weeks of treatment. Global asthma scores did not change significantly (p = 0.2). Geometric mean PC20 methacholine improved significantly after 4 weeks of intranasal beclomethasone, but not after placebo (p = 0.04). Daily morning and evening rhinitis symptom scores were lower in patients treated with intranasal corticosteroids over the first 4 weeks of treatment, but carryover effect of steroids precluded comparative analysis of the second 4-week block (morning p = 0.06, evening p = 0.03). Morning asthma scores tended to decrease (p = 0.07). Evening asthma scores were significantly decreased at weeks 2 and 3 (p = 0.001, p = 0.02, respectively). No change in peak expiratory flow rate was seen. This study confirms that treatment of inflammation in the upper airways indirectly improves asthma symptoms and decreases bronchial hyperreactivity. Ignoring inflammation in the upper airway may lead to suboptimal results in asthma treatment.", "To determine the effect of early administration of high-dose intravenous corticosteroids on duration of emergency room treatment and hospital admission rate in patients with acute asthma.\n Randomized, double-blind, placebo-controlled trial.\n The emergency room of a large, urban hospital with primary and referral care responsibilities.\n Eighty-one patients from 18 to 45 years of age with acute bronchial asthma and without pneumonitis or other serious underlying illnesses were studied on 91 occasions and were randomly assigned to control or experimental groups.\n The steroid group received 125 mg of intravenous methylprednisolone whereas the control group received intravenous normal saline 30 minutes after initial treatment. Additional treatment included aerosolized metaproterenol and oral theophylline therapy. Six hours after study entry, remaining patients were treated with 40 mg of intravenous methylprednisolone. Hospitalization was mandatory if total treatment time was greater than 12 hours.\n Age, sex, peak expiratory flow at entry, and prevalence of recent corticosteroids use were similar in both groups. Duration of emergency room treatment was 6.7 +/- 4.2 (SD) hours in the steroid group and 6.3 +/- 4.1 hours in the control group (P = 0.66). Hospitalization was necessary in 18% (95% CI, 7% to 30%) of the steroid group and in 13% (CI, 3% to 22%) of the control group. Frequency of return visits for acute asthma 2 days after emergency room discharge was 11% (CI, -1% to 22%) in the steroid group and 13% (CI, 2% to 23%) in the control group.\n These results fail to show any benefit for early administration of corticosteroids in patients with acute asthma. Routine administration of corticosteroids on initial presentation in such patients may not be warranted." ]	As monotherapy, inhaled corticosteroids display superior efficacy to anti-leukotrienes in adults and children with persistent asthma; the superiority is particularly marked in patients with moderate airway obstruction. On the basis of efficacy, the results support the current guidelines' recommendation that inhaled corticosteroids remain the preferred monotherapy.
CD001233	[ "3475231", "11883349", "7800329", "2690305", "3514368", "7052115", "850563", "3504454", "2242793", "8559529", "1398272", "8559528", "6945046", "2014076", "12814527", "3051043", "3480840", "9621474", "3860789", "10554936", "10765510", "9846707", "7789590", "1550149", "7943077", "364917", "791584", "7956549", "8598837", "7501332", "1554660", "1317643", "11818106", "9464723", "8191328", "2406438", "780062", "7675378", "3277875", "9307536", "2264174", "14562597", "2712914", "8781697", "7018166", "2094145", "3250183", "16049380", "6576807", "392623", "8827572", "10862852", "8560996", "7023173", "3548209" ]	[ "[Comparison between prostaglandin E2 gel and oxytocin in medically indicated labor induction].", "A randomized trial of vaginal prostaglandin E2 for induction of labor. Insert vs. tablet.", "A randomized trial of management of pre-labor rupture of membranes at term in multiparous women using vaginal prostaglandin gel.", "[Artificial induction of labor at term for medical reasons. Comparison of 2 technics for labor induction, oxytocin + early artificial rupture of the membranes versus prostaglandin E2 vaginal gel. Open randomized controlled study].", "[Multicenter experiences with the intracervical administration of a new PGE2 gel in labor induction].", "Induction of labour: a comparison of a single prostaglandin E2 vaginal tablet with amniotomy and intravenous oxytocin.", "Early labor initiation with oral PGE2 after premature rupture of the membranes at term.", "Cervical ripening and labor outcome with preinduction intracervical prostaglandin E2 (Prepidil) gel.", "Induction of labour: the effect of vaginal prostaglandin or i.v. oxytocin--a matter of time only?", "Prostaglandin E2 gel for cervical ripening in patients with an indication for delivery.", "Labor characteristics of uncomplicated prolonged pregnancies after induction with intracervical prostaglandin E2 gel versus intravenous oxytocin.", "A randomized comparison of prostaglandin E2, oxytocin, and the double-balloon device in inducing labor.", "A simpler approach to labor induction using lipid-based prostaglandin E2 vaginal suppository.", "Does prostaglandin confer significant advantage over oxytocin infusion for nulliparas with pre-labor rupture of membranes at term?", "Trial of extra amniotic saline infusion with oxytocin versus prostaglandin E2 pessary for induction of labor.", "Prostaglandin E2 gel compared to oxytocin for medically-indicated labour induction at term: a controlled clinical trial.", "Prostaglandin E2 vaginal suppository for induction of labour: an efficient, safe and popular method.", "Induction of labor by intracervical prostaglandin gel and oxytocin infusion in primigravid women with unfavorable cervix.", "Comparison of intravenous oxytocin and vaginal prostaglandin E2 gel in women with unripe cervixes and premature rupture of the membranes.", "Prelabour rupture of the membranes at term--no advantage of delaying induction for 24 hours.", "Randomized trial of administration of prostaglandin E2 gel for induction of labor in the morning or the evening.", "A randomized comparison of vaginal prostaglandin E2 with oxytocin plus amniotomy for induction of labour in women with intermediately ripe cervices.", "Induction of labor utilizing vaginal vs. intracervical prostaglandin E2.", "Prostaglandin E2 for induction of labor in patients with premature rupture of membranes at term.", "Cervical ripening before induction of labor: a randomized trial of prostaglandin E2 gel versus low-dose oxytocin.", "Ripening of the uterine cervix and induction of labour at term with prostaglandin E2 in viscous gel.", "Double-blind trial of prostaglandin F2alpha and oxytocin in the induction of labour.", "[15-Methyl-PGF2 alpha vaginal suppository for induction of term labor].", "Induction of labor compared with expectant management for prelabor rupture of the membranes at term. TERMPROM Study Group.", "A randomized trial of two preparations of vaginal prostaglandin for pre-induction cervical ripening.", "Role of prostaglandin in the management of prelabour rupture of the membranes at term.", "Induction of labor by vaginal prostaglandin E2. A randomized study comparing pessaries with vaginal tablets.", "Labor induction with vaginal misoprostol and extra-amniotic prostaglandin F2alpha gel.", "A randomized trial comparing vaginal and cervical prostaglandin gel for cervical ripening and labor induction.", "Mid-trimester termination of pregnancy--a randomised controlled trial of two prostaglandin regimens.", "Intracervical prostaglandin in postdate pregnancy. A randomized trial.", "A randomised controlled trial of an oral solution of prostaglandin E2 and oral oxytocin used immediately after low amniotomy for induction of labour in the presence of a favourable cervix.", "Premature rupture of membranes in nulliparas at term with unfavorable cervices: a double-blind randomized trial of prostaglandin and placebo.", "The efficiency of prostaglandin E2 vaginal suppositories versus intracervical prostaglandin gel for induction of labor in patients with unfavorable inducibility prospects.", "Randomised trial of one versus two doses of prostaglandin E2 for induction of labour: 1. Clinical outcome.", "[Induction of labor. Prostaglandin E2 vaginal tablets compared with intravenous oxytocin for induction of labor in premature rupture of the membranes and immature cervix].", "Vaginal misoprostol for induction of labour: a more effective agent than prostaglandin F2 alpha gel and prostaglandin E2 pessary.", "Premature rupture of membranes near term: induction of labor with endocervical prostaglandin E2 gel or intravenous oxytocin.", "Randomised trial of outpatient induction of labor with vaginal PGE2 at 40-41 weeks of gestation versus expectant management.", "Stimulation of labor in cases of premature rupture of the membranes at or near term. A consecutive randomized study of prostaglandin E2-tablets and intravenous oxytocin.", "Vaginal administration of PGE2 for induction of labor stimulates endogenous PGF2 alpha production.", "A comparison of oral prostaglandin E2 tablets with intravenous oxytocin for stimulation of labor after premature rupture of membranes at term.", "A randomized trial of prostaglandin E2 gel and extra-amniotic saline infusion with high dose oxytocin for cervical ripening.", "Controlled study comparing vaginal prostaglandin E2 pessaries with intravenous oxytocin for the stimulation of labour after spontaneous rupture of the membranes.", "Controlled trial of induction of labor by vaginal suppositories containing prostaglandin E2.", "Controlled comparison of induction versus expectant care for prelabor rupture of the membranes at term.", "Extra-amniotic saline, laminaria, or prostaglandin E(2) gel for labor induction with unfavorable cervix: a randomized controlled trial.", "Cervical ripening and induction of delivery by local administration of prostaglandin E2 gel or vaginal tablets is equally effective.", "Induction of labor with and without primary amniotomy. A randomized study of prostaglandin E2 tablets and intravenous oxytocin.", "Induction of labor with intravenous oxytocin or vaginal PGE2 suppositories. A randomized study." ]	[ "The use of prostaglandins (PG) increasingly replaces the \"classical\" method of induction of labour by means of oxytocin and amniotomy, the last-named method being associated, especially in women with an unripe cervix, with side effects like prolonged labour and a higher rate of obstetric surgery. In this study the point of interest was whether prostaglandins offer any advantages over the classical method in respect of efficacy and maternal and foetal tolerance. 99 patients subdivided into primiparae and multiparae were randomly assigned to group A or B. In group A labour was induced with 1 mg resp. 2 mg PGE2 intravaginally at an interval of 6 hours. In group B the method of induction consisted of intravenous oxytocin and amniotomy. The success rate of induction was almost equal in both groups. However, in those patients where PGE2 induction did not succeed and who could not be delivered within 12 hours the cervical score was significantly improved in comparison to the oxytocin group. Based on the experience reported in the literature, one might speculate that an increased dosage could still improve the results of vaginally administered PGE2 gel.", "To compare the efficacy and safety of a prostaglandin E2 (PGE2) vaginal insert with PGE2 administered as a vaginal tablet.\n A randomized, observational study was performed. Women requiring induction of labor were randomly assigned to receive either a 10-mg PGE2 vaginal insert (group 1, n = 100) or 3-mg PGE2 tablets twice at six-hour intervals (group 2, n = 100). The primary efficacy outcome variable was vaginal delivery within 24 hours of insertion. The criteria for safety were the occurrence of uterine hyperstimulation, abnormal fetal heart rate patterns, use of beta 2-sympathomimetic drugs and fetal outcome.\n No differences in terms of vaginal delivery or cesarean section within 24 hours of induction were found. The cesarean section rate was 21% in group 1 and 22% in group 2. The interval from insertion of the induction agent to the onset of regular uterine contractions and the insertion-to-delivery interval were not different between the two cohorts. No difference in the frequency of uterine hyperstimulation, use of beta 2-sympathomimetic drugs, abnormal fetal heart rate patterns, fetal outcome, or oxytocin and analgesic requirements were found. In seven of eight patients in group 1 who experienced uterine hyperstimulation, removal of the insert was sufficient to stop it, whereas in group 2, of nine cases, eight needed medical interventions to end hyperstimulation (P = .003).\n The continuous release of PGE2 from the vaginal insert permits controlled induction of labor, and easy removal of the drug in cases of uterine hyperstimulation is possible.", "To compare conservative management of pre-labor spontaneous rupture of membranes (SROM) with the use of prostaglandin (PG) E2 in healthy parous women at term (gestational age at least 37 weeks).\n An open randomized study was conducted with 100 parous women; 50 were treated conservatively for 24 hours, and 50 were managed actively using PGE2 gel (1 mg), administered at admission and repeated 6 hours later if labor was not established. Both groups received intravenous oxytocin if labor did not start within 24 hours after admission.\n The use of PGE2 gel led to a significant reduction in the mean interval (+/- standard error of the mean) from SROM to onset of labor: 17.26 +/- 1.51 hours in the conservative group versus 6.50 +/- 1.23 in the PGE2 group. A significantly smaller proportion of subjects required oxytocin in the PGE2 group (12 versus 38%, P < .02). The two groups were comparable with respect to analgesic requirements. Within 24 hours of SROM, 80% of the women in the PG group and 56% in the conservative group had delivered (P < .02). Most women delivered vaginally, 96% of those managed conservatively and 100% of those managed actively with PGE2.\n Active management using PGE2 gel in parous women with pre-labor SROM significantly improves the time to delivery without influencing the cesarean rate or fetal-maternal infective morbidity.", "Labor induction for medical reasons is a situation rather well-controlled by the combination: \"oxytocin-amniotomy\" when the cervix is favorably open. However, new induction techniques are currently under study, especially vaginal administration of PGE2 which presents the advantage of being simple to administer and better accepted by the patients. This study compared the classical technique, oxytocin perfusion and early artificial rupture of the membranes, with the vaginal administration of PGE2 gel (first dose: 1 mg, second dose 1 or 2 mg, six hours later). The success rate of both techniques is comparable, approximately 70 p. cent. Also, the times between amniotomy and delivery are identical, approximately 5 hours. On the contrary, the lapses of time between the onset of the induction and the delivery, vary significantly, being always longer in the PGE2 group. However, the dose of vaginal PGE2 gel as well as the time of artificial membrane rupture could be modified in order to decrease the delay of the effect.", "With the participation of four Swiss obstetric clinics, medically indicated inductions of birth (with living fetuses) were performed using a new, stable PGE2 gel, and documented according to a uniform protocol. The study was conducted to investigate the efficacy of 0.5 mg of PGE2, in 2.5 ml of a vehicle (Triacetin) not yet commercially available, for local cervical maturation (n = 41). Thirty-nine patients selected by prospective randomization, in whom birth was induced conventionally, served as a control group. The efficiency of the prostaglandin gel alone or respectively with additional administration of oxytocin was evaluated on the basis of the clear changes in the cervical findings observed within 12 or respectively 24 hours, the spontaneous births, or, in the case of cesarean deliveries, according to the pelvic score. Application of PGE2 alone led to impressive changes of the cervix score and, in 34 of the 41 cases, to regular contractions after an average time of 87 minutes. After 12 hours, prior to administration of oxytocin, 43% of the patients were already delivered. The combination of locally applied PGE2 gel with conventional oxytocin induction significantly increases the number of successful inductions. The percentage of unsuccessfully attempted inductions was reduced to 24% in the PGE2 gel group as compared to 44% in the control group.", "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.", "Two groups of healthy women at term, who were not in labor 3 hours after premature rupture of the membranes, were studied. In one group labor induction with oral prostaglandin E2 (PGE2) was begun 3 hours after rupture, and in the other group intravenous oxytocin induction was begun 12 hours after rupture. PGE2 was successful in initiating active labor in 88% of women treated. Of the women who were observed for 12 hours, one-half began labor spontaneously during that time. Women in whom labor was induced with PGE2 given 3 hours after rupture of the membranes had a shorter interval of rupture to delivery, a lower cesarean section rate, and shorter postpartum hospitalization. Although significant bradycardia did not occur in fetuses of those women given PGE2, 10% of infants whose mothers were receiving oxytocin were delivered by cesarean section for this reason. It is concluded that oral PGE2 is safe and effective for induction of labor in women with premature membrane rupture. The benefits, to both mother and fetus, of a shorter latent period are discussed.", "Delivery with an unfavorable cervix using oxytocin is frequently unsuccessful. Used widely in Europe and increasingly in this country, locally applied prostaglandin E2 appears to improve labor induction. The present study prospectively evaluated the efficacy and safety of a prostaglandin gel (0.5 mg) placed intracervically. The use of the gel, when compared to a control group who received no pretreatment prior to labor induction, resulted in improved Bishop scores (7.5 +/- 1.0 vs. 1.8 +/- 0.3, P less than 0.0001), reduced induction to delivery intervals (10.1 +/- 2.1 vs. 20.6 +/- 2.0 hours), reduced oxytocin infusion duration (10.0 +/- 2.1 vs. 20.0 +/- 2.3 hours. P less than 0.0001) resulting in a lower cesarean delivery rate, 26 vs. 47 per cent (P greater than 0.05). Thirty-two per cent of patients receiving the prostaglandin gel labored and delivered within 12 hours and required no oxytocin. In addition, the use of prostaglandin E2 gel appeared safe in that no patient experienced an untoward reaction. Two cases of uterine hyperstimulation occurred that required uterine tocolysis but were not associated with fetal distress. The use of prostaglandin gel appears to be a safe and effective method to improve cervical inducibility in patients undergoing induction for a variety of maternal and fetal indications.", "Ninety-one pregnant women with unfavourable cervix (Bishop score no higher than 6) were randomly allocated to induction of labour with either prostaglandin E2 suppositories 2.5 mg 1-2 a day or i.v. oxytocin 4-32 mU/min. The induction procedure was carried on for 2 days. For statistical comparison of efficacy, life table analysis and the logrank test were used with vaginal delivery as the aimed 'event'. Prostaglandin suppositories were more efficient after 12 h (p less than 0.025) and 24 h (p less than 0.005), whereas no difference in efficacy was observed after 48 h. Vaginal delivery was obtained within 48 h in 74% of the women in the prostaglandin group and in 70% in the oxytocin group. No difference was observed in methods of delivery or neonatal Apgar scores, though, in neonates delivered vaginally within 2 days, lowered umbilical artery blood pH values were found after prostaglandin E2 suppositories (p less than 0.05). The patients attitude toward the method of induction was highly in favour of the prostaglandin suppositories. Prostaglandin E2 suppositories are considered excellent for induction of labour if delivery has to be within 24 h, whereas the two methods are equally effective after 48 h.", "To determine if labor can be induced safely and efficiently in patients with a medical or obstetric indication for delivery before 41 completed weeks of gestation by pre-induction cervical ripening with prostaglandin (PG) E2 gel.\n One hundred eighteen women with confirmed indication for induction of labor before 41 completed weeks were randomized in a double-blind fashion to either intracervical PGE2 gel or placebo before induction by a standard oxytocin protocol. Data regarding the change in Bishop score, interval to complete dilation, maximal oxytocin dose required to establish labor, and route of delivery were collected. Apgar scores and umbilical artery pH were also recorded.\n The maximum oxytocin dose required to establish progressive labor was significantly lower in the PGE2 group (10.06 +/- 8.50 versus 13.35 +/- 9.27 mU/minute, P = .014). The cesarean rate was also significantly lower in the PGE2 group (13.1 versus 31.6%, P = .016).\n Pre-induction intracervical deposition of 1 mg PGE2 gel decreased the amount of oxytocin required to induce progressive labor and decreased the cesarean rate in patients who had medical or obstetric indications for delivery before 41 completed weeks. This was accomplished without negative effect on Apgar score or umbilical artery pH.", "Labor characteristics after intracervical application of 0.5 mg prostaglandin (PG) E2 gel (n = 83) versus intravenous administration of oxytocin (n = 82) for labor induction were investigated in uncomplicated prolonged pregnancies with unripe cervix. The induction to delivery time as well as the total oxytocin dose were significantly reduced in the PGE2 group (p < 0.001). Cesarean sections, instrumental deliveries and fetal distress had the same frequency, but the failures of trial were significantly higher in the oxytocin group than in the PGE2 group (20.7 vs. 6%, p < 0.01). Twenty-four percent of women needed a second PGE2 dose, and almost half of the women in the PGE2 group experienced 'spontaneous' labor. More neonates in the oxytocin group had 5-min Apgar scores < 7 (p < 0.05). Intracervical PGE2 gel application is superior to intravenous oxytocin in terms of shortening the induction-delivery interval and increasing the frequency of successful vaginal delivery. In addition, it is safe for mother and fetus.", "To compare the efficacy of three methods for ripening and dilating the unfavorable cervix for induction of labor.\n Pregnant women having an indication for induction of labor with a singleton vertex fetus, intact membranes, and Bishop score of no more than 4 were randomized to one of three induction methods: intravaginal prostaglandin (PG) E2 tablets (3 mg) followed by a second dose if labor did not start; continuous intravenous oxytocin drip; or the Atad Ripener Device, with inflation of both balloons and removal after 12 hours. For all patients, the cervix was assessed by the same investigator before induction and 12 hours later.\n Thirty subjects were included in the PGE2 group, 30 in the oxytocin group, and 35 in the Atad Ripener Device group. The postpartum course was comparable in all. The change in Bishop score in the PGE2 and Atad Ripener Device groups was significantly better than in the oxytocin group (median and range of 5[0-9] and 5[0-7], respectively, versus 2.5 [0-9]; P < .01). Cervical dilation more than 3 cm was more frequent in the Atad Ripener Device group compared with both the PGE2 and oxytocin groups (85.7 versus 50 and 23.3%, respectively; P < .01). The trial of induction failed in only two patients (5.7%) in the Atad Ripener Device group, compared with six (20%) in the PGE2 and 16 (53.3%) in the oxytocin groups (P < .001). Mean (+/- standard deviation) induction-to-delivery interval was 21.3 +/- 7.0 hours in the Atad Ripener Device group, 23.2 +/- 12.5 hours in the PGE2 group, and 28.2 +/- 14.7 hours in the oxytocin group. The success rate for vaginal delivery was significantly better in the Atad Ripener Device and PGE2 groups compared with the oxytocin group (77.1 and 70%, respectively, versus 26.7%; P < .01).\n The Atad Ripener Device had a significantly better success rate for cervical dilation and a lower failure rate than those for PGE2 and oxytocin. The PGE2 and Atad Ripener Device groups had better results than the oxytocin group in regard to Bishop score change and induction-to-delivery interval. The Atad Ripener Device may be a superior method for cervical ripening and labor induction in patients with unfavorable cervices.", "The outcome of labor induced by use of a glyceride-based vaginal suppository of prostaglandin E2 (PGE2) inserted 3 hours before amniotomy, when the cervix is favorable, has been assessed. Using 5 mg PGE2 for primigravidas and 2.5 mg for multigravidas, 63% of the former and 81% of the latter established labor and were delivered of their infants without oxytocin augmentation, allowing ambulation during early labor. No maternal complications were detected as a result of the PGE2 treatment. Compared with patients undergoing conventional induction by amniotomy and immediate oxytocin titration there was no difference in the duration of labor, with a few patients establishing labor and giving birth quickly with both induction methods. Fetal distress was less common following PGE2 treatment than following conventional induction, with three patients in each group requiring delivery by cesarean section. Cephalopelvis disproportion in the second stage of labor requiring cesarean section to deliver occurred more frequently in the prostaglandin-treated group, possibly as a result of reduced upper segment contractility in the first stage of labor with subsequent poor fetal head molding. Epidural analgesia and postpartum hemorrhge were both reduced following PGE2-induced labor.", "Ninety-four nulliparous women with a poor cervical score (less than 6) who had premature rupture of membranes at term were randomized by sealed envelope into two groups. One group received immediate stimulation of labor with oxytocin infusion. The second group received two prostaglandin E2 (PGE2) 3-mg pessaries 4 hours apart, followed by oxytocin infusion, if necessary. The interval between initiation of therapy to onset of labor was significantly longer in the PG group, but the length of labor was similar in both groups. The maximum dose of oxytocin needed was significantly higher in the oxytocin group. The cesarean delivery rate in the oxytocin group was 14.9%, compared with 19.1% in the PG group (not significantly different). All seven cesareans in the oxytocin group and seven of nine in the PG group were for failed stimulation of labor. Neonatal Apgar scores at 1 and 5 minutes and admission to the neonatal intensive care unit were similar in the two groups. The incidence of maternal and neonatal infection was small and was not different in the two groups. The use of PGE2 3-mg pessaries 4 hours apart, followed by oxytocin infusion if necessary, did not confer any benefit over the use of intravenous oxytocin in obstetric or neonatal outcome when both agents were started a few hours after admission.", "To determine the effectiveness and safety of cost-effective extra-amniotic saline infusion (EASI) and simultaneous intravenous oxytocin infusion versus prostaglandin E2 vaginal pessary (PGE2) for induction of labor.\n Prospective randomized comparative study.\n Labor room at the Mother and Child Health Centre, PIMS, Islamabad from September 2000 to December 2001.\n Women with singleton alive pregnancies and Bishop score < or =6, requiring induction of labor at > or =37 weeks gestation were randomly assigned to induction either with PGE2 3 mg vaginal pessary in two doses 6 hourly or EASI for 12 hours with simultaneous intravenous oxytocin infusion. Artificial rupture of membranes was done 12 hours post-induction and oxytocin infusion started in PGE2. Main outcome measures were induction delivery interval and the mode of delivery. Secondary outcome measures were the change in modified Bishop score 6 hours postinduction and neonatal outcome in the two induction modes.\n After 4 exclusions, 100 women were recruited in each arm. Mean induction delivery interval was 11.1 and 14.3 hours (p=.00) in PGE2 and EASI respectively. The cesarean rate was 11% and 15% (p=0.4) in PGE2 and EASI respectively. Mean Bishop score at induction was 3.2 in PGE2 and 3.1 in EASI, while after 6 hours it was 4.8 and 6.8 (p=0.00) respectively. Mean APGAR scores at 1 and 10 minutes were identical that is 6.2 and 8.6 respectively.\n Both the modes of induction were equally safe and effective in terms of the mode of delivery and APGAR score. EASI, however, had more rapid cervical ripening and shorter induction delivery interval.", "A clinical trial was carried out to compare the efficacy and tolerance of two modes of induction of labour: vaginally administered prostaglandin E2 gel vs intravenous perfusion of synthetic oxytocin. Fifty women with pregnancy at or near term in whom prompt vaginal delivery was clinically indicated were divided at random into sub-groups of 25 each. Initial dose of PGE2 gel was 1 mg followed by another application of 1 mg or 2 mg 6 hours later in case active labour stage has not been reached. Progressive oxytocin perfusion began with 1 mU/min., being increased gradually every 20 minutes until efficacious uterine dynamics were attained. Data were recorded on entry of age, parity, gestation age, cervical dilatation, Bishop score, indication for induction. Continuous materno-foetal monitoring was carried out during the induction period. Results were evaluated from induction/delivery time, type of delivery, maternal and foetal condition, and any side-effects which developed. Apart from a higher number of instrumental deliveries in the PGE2 gel series, which was not related to the induction method, there was no significant difference between any of the variables evaluated, both methods producing active labour in approximately 70% of the patients within 12 hours. The authors stress, however, the convenience, both for patients and hospital staff, of the administration of an intravaginal induction agent over a systemic therapeutic method of induction.", "Two different methods for induction of labour were randomly used in 100 women with a favourable cervix. The patients were treated with either prostaglandin vaginal suppositories containing 2.5 mg PGE2 in a base of Witepsol S55 (Dynamit Nobel) or intravenous infusion of oxytocin. The PGE2 vaginal suppository was significantly more efficient than the intravenous infusion of oxytocin in relation to the time interval from the start of induction of labour to delivery. Also the percentage of women who delivered within 48 hours (success rate) was higher in the suppository group. Significantly more women in the suppository group found this induction method recommendable.", "The rate of Cesarean Section for failed induction of labor and maternal and fetal compilations are high when labor is induced in a nulliparas women with an unripe cervix by amniotomy and oxytocin infusion. Prostaglandins (PG) in different forms have been used for ripening the cervix with an aim of reducing these problems. A prospective randomized trial was performed on one hundred primigravid women between 37 and 42 weeks of gestation with singleton pregnancy, cephalic presentation and unfavorable cervix (Modified Bishop Score < or = 5) in the department of Obstetrics & Gynaecology of Institute of Postgraduate Medicine & Research from 1st May 1996 to 30th April 1997. In this study the efficiency of prostaglandin E2 intracervical (PGE2 IC) gel in induction of labor in a group of primigravid women with unripe cervix was assessed and compared with another group with similar characteristics using oxytocin infusion and artificial rupture of membrane (ARM). The Modified Bishop Score (MBS), interval between IOL and onset of labor and the duration of labor after insertion of PGE2 gel was significantly different from those of oxytocin infusion group. But the Apgar Score at 1 & 5 min had shown no statistically significant difference. Any significant difference could also not be detected in the mode of delivery between the two induction group. The proportion of emergency Cesarean Section (CS) was high in the oxytocin infusion group than that of in the prostaglandin group. There was also no significant difference regarding the acceptability of both the induction methods.", "To induce cervical priming and labor, 20 nulliparous term pregnant women with premature rupture of the membranes and unfavorable cervical states were randomly given either oxytocin intravenously or 4 mg prostaglandin E2 in gel intravaginally. One of ten women receiving oxytocin had a favorable cervical state within five hours and vaginal delivery within 24 hours after the start of the infusion compared with six of ten women after prostaglandin E2 gel application. This difference is statistically significant (P less than .01). The number of instrumental deliveries was nine (four cesarean sections and five vacuum extractions) in the oxytocin-treated patients compared with only two vacuum extractions in women who received prostaglandin E2 gel. This difference is also statistically significant (P less than .01, Fischer exact test). In a subsequent open study, 4 mg prostaglandin E2 gel was applied vaginally to 17 term pregnant women of mixed parity with premature rupture of the membranes and unfavorable cervixes. In 12 women a favorable cervical state was achieved within five hours after gel application, and all these women were delivered within 24 hours. None of the women required cesarean section but two required delivery by vacuum extraction. There were no perinatal losses, but two infants in the oxytocin-treated group had Apgar scores less than 7 at five minutes. At pediatric follow-up after two and six months, all infants were normal. In both obstetric and perinatal outcome prostaglandin E2 gel thus seems to be superior to oxytocin for labor induction in term pregnant patients with premature rupture of the membranes and unfavorable cervixes.", "We performed a prospective randomized study to compare maternal and fetal outcomes in pregnancies with prelabour rupture of the membranes (PROM) at term with early induction of labour or expectant management, 126 women with singleton pregnancy, cephalic presentation and gestational duration > or = 37 weeks, were randomized either to immediate induction of labour with oxytocin (Group 1) (n=52), or conservative management (Group 2) (n=74). Women who constituted Group 2 were divided into 2 groups. The first group (Group 2A) (n=25) included women in whom spontaneous labour did not begin after a waiting period of 24 hours, in which case labour was induced with oxytocin i.e. expectant management. The second group consisted of women (Group 2B) (n=49) in whom labour began spontaneously within 24 hours. The base Caesarean section rate was significantly higher in Group 2 (28.4%) (p<0.05). The rates of Caesarean section in the Groups 1-2A-2B were 19.2%, 60%, and 12.2%, respectively for nulliparous and parous women together. The rate of fetal distress was significantly higher in Group 2 (p<0.05). For determining maternal outcomes, the other parameters such as clinical chorioamnionitis, fever before or during labour, receiving antibiotics before or during labour, postpartum fever, analgesia, anaesthesia did not differ in Groups 1 and 2. Women in Group 1 went into active labour sooner, had fewer digital vaginal examinations, had a shorter interval between membrane rupture and delivery, and spent less time in the hospital before delivery than those in Group 2 (p<0.05). Babies in Group 2 were more likely to receive antibiotics, and more likely to stay in an intensive care nursery for more than 24 hours, and more likely to receive ventilation after initial resuscitation than those babies in Group 1. For developing apnoea and hypotonia, there was no significant difference between Groups 1 and 2. However, for babies in Group 2A there was a significant difference. We conclude that immediate induction of labour with oxytocin does not increase the risk of Caesarean section, compared with a practice of expectant management. Women at term with prelabour rupture of the membranes should therefore be reassured that immediate induction with oxytocin currently appears to be the best policy with respect to maternal and neonatal morbidity.", "To compare the outcome of induction of labor and patient's preferences using a protocol with the first dose of prostaglandin E2 endocervical gel in the evening versus a protocol with the first dose in the morning.\n We performed a randomized trial comparing administration of prostaglandin E2 endocervical gel in the morning with administration of prostaglandin E2 gel in the evening, followed if necessary by a second dose being given after six hours if labor had not started or the cervix was still unripe. Formal induction of labor by amniotomy and oxytocin infusion was performed the morning after the initial prostaglandin E2 dose. Patients' preferences were assessed using a questionnaire that was completed after delivery.\n Tertiary care hospital in the Netherlands with 1,600 deliveries per year.\n One-hundred and twenty-six women with viable singleton pregnancies at term who had induction of labor with prostaglandins.\n Time of delivery (daytime, evening or night) and patient's satisfaction.\n Fifty-eight women were allocated for administration of gel in the morning, whereas 68 had their gel in the evening. Administration of gel in the evening did not significantly reduce delivery between 23.00 hours and 08.00 hours, although there was a reduction in delivery between 23.00 hours and 08.00 hours in nulliparae. None of the multiparous women delivered between 18.00 hours and 23.00 hours after induction of labor in the evening. The relative risk for delivery by vacuum or forceps was increased after allocation of gel in the evening (4.2; 95% confidence limits 1.4 to 13). Patients' preferences favored administration of gel in the morning.\n There was no benefit in starting induction of labor with prostaglandin E2 in the evening, compared with starting in the morning.", "To compare the effects of oxytocin and amniotomy or vaginal prostaglandin E2 (PGE2) for induction of labour.\n We conducted a randomized clinical trial. Eligible for the trial were women with normal pregnancy, parity 0-3, with intact membranes, >40 weeks of gestation documented by ultrasound examination before 20 weeks gestation, observed in a network of 13 general and teaching hospitals in Italy. Inclusion criteria were cervical Bishop's score 5-7, less than six uterine contractions per hour, single pregnancy, cephalic presentation, no history of cesarean section and uterine surgery. Eligible women were randomly assigned by phone to oxytocin plus amniotomy (163 women) or vaginal PGE2 2 mg, two doses at 6-h intervals (157 women).\n Overall, 50 women (15.6%) delivered by cesarean section, 22 (13.5%) randomized to oxytocin, and 28 (17.8%) randomized to PGE2 (not significant). Twelve hours after randomization, induction had failed in 26 women of the 163 randomized to oxytocin plus amniotomy (21.6%) and 34 out of the 157 randomized to PGE2 (15.9%): the difference was not significant. Neonatal outcome was similar in the two groups.\n This study did not find marked differences in labour and neonatal outcome between women randomized to oxytocin plus amniotomy or vaginal PGE2. A shorter induction delivery interval in the group receiving amniotomy and oxytocin after PGE2 priming was observed.", "To compare the efficacy of intracervical vs. vaginal prostaglandin E2 (PGE2) gel for induction of labor.\n Sixty-eight women scheduled for elective induction of labor at term were randomized to receive either 0.5 mg intracervical PGE2 (I/C group, n = 37) or 2 mg vaginal PGE2 gel (Vag group, n = 31) on a 6-hourly basis for a maximum of three doses.\n Three participants who delivered by cesarean section soon after gel administration were excluded from further analysis. Twenty-nine of 30 (97%) in the Vag group were successfully induced compared with 23 of 35 (66%) in the I/C group (P < 0.01). The induction-active labor intervals were 8.0 +/- 5.4 h for the Vag group and 23.1 +/- 27.6 h for the I/C group (P = 0.002). The induction-delivery intervals were 12.4 +/- 6.3 h for the Vag group and 29.8 +/- 29.1 h for the I/C group (P = 0.001). Uterine hyperstimulation and perinatal outcome were similar in both groups.\n Vaginal PGE2 was more efficacious than intracervical PGE2 in inducing labor.", "A prospective study comparing three management schemes for patients at term with premature rupture of membranes was performed.\n One hundred forty patients were randomized to one of three study groups: prostaglandin E2, placebo, or oxytocin. Patients randomized to prostaglandin E2 and placebo received vaginal suppositories containing 3 mg prostaglandin E2 or glycerin only, respectively; suppositories were administered in a double-blind fashion, on one or two occasions, 6 hours apart. Oxytocin was given only if labor was not established after 12 hours or to augment inadequate labor. In patients randomized to oxytocin labor was induced with intravenous oxytocin. The time interval to delivery, delivery outcome, and complications were analyzed.\n Patients receiving prostaglandin E2 were more likely to be in labor after one suppository and to be delivered without the addition of oxytocin when compared with placebo. The time interval to delivery was shorter with prostaglandin E2 and oxytocin induction versus placebo (\"expectant management\"). The incidence of maternal infection was lowest in patients with labor induced by prostaglandin E2. Although the overall cesarean section rate was low, there was a trend toward a lower rate with prostaglandin E2 induction. No adverse effects were observed with prostaglandin E2.\n Prostaglandin E2 can be used successfully to induce labor after premature rupture of membranes at term with greater ease of administration when compared with oxytocin.", "The purpose of this study was to compare prostaglandin E2 gel and a low-dose infusion of oxytocin for cervical ripening before labor induction.\n A total of 158 women were randomized to receive either two intracervical doses of 0.5 mg prostaglandin E2 gel 6 hours apart or 12 hours of intravenous oxytocin up to 4 mlU/min. After cervical ripening labor was induced with high-dose oxytocin infusion and amniotomy.\n There was no difference between the prostaglandin E2 and low-dose oxytocin groups in the likelihood of being in labor or having a Bishop score favorable for induction after ripening (64.2% vs 52.0%, p = 0.12) or in the incidence of vaginal delivery (75.9% vs 74.7%). Prostaglandin E2-treated patients were delivered sooner (20.2 +/- 8.1 hours vs 25.0 +/- 10.5 hours, p = 0.002). Among delivered patients the likelihood of vaginal delivery within 24 hours was greater with prostaglandin E2 ripening (63.7% vs 47.2%, p = 0.04), but there was no difference at 36 hours (76.2% vs 75.0%). Uterine hyperstimulation and fetal distress during ripening occurred only in the prostaglandin E2 group, at a rate of 4.8%.\n After cervical ripening with prostaglandin E2 gel or low-dose oxytocin vaginal delivery can be expected in three fourths of patients within 24 to 36 hours. We recommend that patients with an unfavorable cervix who require delivery undergo cervical ripening and induction of labor rather than automatic delivery by cesarean section.", "In order to achieve ripening of the uterine cervix or induce labour in patients at term with an unfavourable cervical state, 1 mg of prostaglandin E2 (PGE2), suspended in a viscous gel, was instilled into the cervical canal. In a pilot study, 41 patients received the PGE2-gel. Twenty-three of these, (56%), went into labour, and delivery occurred without further stimulation within 15 hours. In the remaining 18 patients, there was a marked improvement of the cervical state, which changed from an average (modified) Bishop score of 2.5 to 6.1 within 24 hours. In a double-blind study comprising 20 nulliparae, 10 received gel containing PGE2 and 10 gel without prostaglandin. Cervical state did not change significantly (Bishop score 3.6 and 4.0) after 24 hours in patients receiving placebo gel. In those receiving PGE2 gel, 8 went into labour and were delivered without further induction within 13 hours. Two patients showed an increase in Bishop score from 3 to 6 and 7, respectively, after 24 hours. They were then induced by oxytocin and delivery occurred after 8 and 10 hours. The results suggest that administration of PGE2 intracervically can induce ripening of the cervix in patients at term with an unfavourable cervical state, and thus facilitate delivery.", "In a random double-blind trial in 28 pregnant women at term, labour was induced with either prostaglandin F2alpha or oxytocin given by intravenous infusion. The results showed that prostaglandin F2alpha was as active as oxytocin and induction was successfully carried out in 24 patients; 3 patients had a caesarean section because of an obstructed labour and 1 patient on oxytocin did not have regular contractions after 10-hours' infusion although she delivered spontaneously 2 days later. No difference was found in the induction--delivery interval in the 8 patients in each group who had early amniotomy (first 90 minutes). No adverse effects were noted in either mother or the child. The authors recommend that to avoid side-effects the dosage of 20 mug prostaglandin F2alpha per minute should not be exceeded and that, although no cardiotocographic abnormalities were noted, this method of control should be used.", "The results of intravaginal 15-methyl PGF2 alpha (PG05) were compared with gemeprost (ONO-802, PGE1 analogue) pessary and oxytocin intravenous infusion for induction of labor at term. A total of 99 primipara with singleton pregnancy and cephalic presentation, accepted for induction, was randomly allocated into 3 groups: group 1, PG05 0.25 mg (n = 33), group 2, ONO-802 0.125 mg (n = 33), and group 3, oxytocin i.v. (n = 33). Among these, 30 cases had plasma PGs (PGE2 and PGF2 alpha) concentration determined before and after induction. Successful treatment was defined as active labor starting within 24 hours following induction or an increase of cervical Bishop score > 3. The success rates were not significantly different among the 3 groups (PG05 88%, ONO-802 100%, and oxytocin 79%), (P > 0.05). No significant difference existed in the plasma prostaglandin concentrations as well. It is suggested that PG05 may be used for induction of labor at term.", "As the interval between rupture of the fetal membranes at term and delivery increases, so may the risk of fetal and maternal infection. It is not known whether inducing labor will reduce this risk or whether one method of induction is better then another.\n We studied 5041 women with prelabor rupture of the membranes at term. The women were randomly assigned to induction of labor with intravenous oxytocin; induction of labor with vaginal prostaglandin E2 gel; or expectant management for up to four days, with labor induced with either intravenous oxytocin or vaginal prostaglandin E2 gel if complications developed. The primary outcome was neonatal infection. Secondary outcomes were the need for cesarean section and women's evaluations of their treatment.\n The rates of neonatal infection and cesarean section were not significantly different among the study groups. The rates of neonatal infection were 2.0 percent for the induction-with-oxytocin group, 3.0 percent for the induction-with-prostaglandin group, 2.8 percent for the expectant-management (oxytocin) group, and 2.7 percent for the expectant-management (prostaglandin) group. The rates of cesarean section ranged from 9.6 to 10.9 percent. Clinical chorioamnionitis was less likely to develop in the women in the induction-with-oxytocin group than in those in the expectant-management (oxytocin) group (4.0 percent vs. 8.6 percent, P<0.001), as was postpartum fever (1.9 percent vs. 3.6 percent, P=0.008). Women in the induction groups were less likely to say they liked \"nothing\" about their treatment than those in the expectant-management groups.\n In women with prelabor rupture of the membranes at term, induction of labor with oxytocin or prostaglandin E2 and expectant management result in similar rates of neonatal infection and cesarean section. Induction of labor with intravenous oxytocin results in a lower risk of maternal infection than does expectant management. Women view induction of labor more positively than expectant management.", "To compare two prostaglandin (PG) E2 preparations for pre-induction cervical ripening in a randomized clinical trial.\n Two milligrams of vaginal PGE2 gel was compared with a vaginal PGE2 3-mg tablet in 200 nulliparous women. Outcomes assessed were induction failure, need for labor augmentation, pain relief requirements, fetal heart rate (FHR) abnormalities, operative delivery rate, induction-to-delivery interval, neonatal condition, and occurrence of uterine hyperstimulation.\n There was no statistical difference in pre- and post-dose cervical scores. Compared with the tablet group, women in the gel group were more likely to have significant FHR abnormalities in early labor (odds ratio [OR] 4.77, 95% confidence interval [CI] 1.15-19.5) requiring cesarean delivery. Fetal heart rate tracings in the active phase of labor were also more likely to be abnormal in the gel group (chi 2 = 4.31, P < .05). Compared with the gel group, women in the tablet group were significantly more likely to require operative delivery for poor progress in labor (OR 2.83, 95% CI 1.20-7.24). Other clinical outcomes were identical, with no significant differences in the overall rate of failed induction, cesarean delivery, rate of assisted delivery, requirement for oxytocin infusion, induction-to-delivery interval, pain relief requirements, or neonatal condition.\n When compared with the PGE2 tablet, the use of PGE2 gel for cervical ripening and labor induction in nulliparous women did not result in significant improvements in labor outcome. Whereas the gel was associated with an increase in significant FHR abnormalities, the tablet was associated with an increase in the rate of operative delivery for poor progress in labor.", "To compare conservative versus prostaglandin management of prelabour rupture of the membranes (PROM) in healthy primigravid women at term.\n A prospective randomized study.\n Labour Ward, Aberdeen Maternity Hospital.\n 230 primigravidae at terms with PROM, 115 allocated to be treated conservatively and 115 to be managed with prostaglandin treatment.\n In the conservatively managed group the women were observed for up to 24 h after hospital admission with PROM. The actively managed group had PGE2 gel (2 mg) instilled into the posterior fornix and if contractions had not commenced, a further dose of PGE2 gel (1 mg) was instilled 6 h later. In both groups, if labour had not established 24 h after admission, intravenous oxytocin was given in escalating doses.\n PROM to delivery interval, oxytocin augmentation, mode of delivery, maternal and neonatal infective morbidity.\n There was a significant reduction in the PROM to delivery interval in the women managed actively with PGE2 gel and fewer women in the PGE2 group required oxytocin augmentation (31% vs 51%). The two managements groups were comparable for intrapartum analgesia, antibiotic treatment, babies requiring admission to the special care nursery unit and delivery by caesarean section.\n The early use of prostaglandin is associated with a significant reduction in PROM to delivery interval without a significant increase in infective morbidity or caesarean section rate. However, the advantages of the conservative approach should not be overlooked. More work is still needed in the management of those women where uterine activity fails to establish within 24 h after PROM.", "A prospective randomized study of 267 pregnant women was undertaken to compare the efficacy of a pharmacy-prepared 3-mg prostaglandin E2 (PGE2) vaginal suppository with a 3-mg PGE2 vaginal tablet for induction of labor and cervical ripening. No statistically significant difference in success frequency was found between the two groups, either on the first day (72% and 74%, respectively; p greater than 0.05) or on the second day (89% in both groups). There was an equal proportion of women requiring oxytocin augmentation in the two groups, but the slower releasing properties of the vaginal tablet were reflected in a longer mean induction--delivery interval of about 4 h for this group. In both the pessary and the vaginal tablet groups, women who had not gone into labor on the first day showed a statistically significant increment in the Bishop score on the morning of the second day. The frequency of cesarean section was the same in both groups, but instrumental deliveries were more frequent in the vaginal tablet group. It is concluded that PGE2 vaginal tablets--a chemically stable alternative to pharmacy prepared pessaries--appear to be effective as regards cervical ripening as well as for labor induction.", "To compare the effectiveness of vaginally administered misoprostol with extra-amniotic prostaglandin F2alpha (PGF2alpha) gel for induction of labor.\n A randomized controlled trial, with women allocated to receive either misoprostol 50 microg intra-vaginally or extra-amniotic PGF2alpha gel 5 mg, was conducted in Harare Maternity Hospital. A total of 152 women were admitted for induction of labor with a term singleton, pregnancy and cephalic presentation were recruited. The main outcome was duration of induction.\n There were no differences in the characteristics of women in the two groups at recruitment. In the misoprostol group there was a significantly reduced need for augmentation of labor with oxytocin (OR=0.36; 95% C.I. 0.17-0.73) and delivery by cesarean section for failure to progress (OR=0.11; 95% C.I. 0.00-0.88). The risk for duration of induction to vaginal delivery exceeding 12, 18 or 24 h was reduced by 18%, 38% and 68%, respectively, but only the risk for duration >24 h was significantly reduced (OR=0.32; 95%C.I. 0.11-0.91). The mean duration of induction was shorter in the misoprostol group, 15.2 vs. 23.6 h (P=0.02). There were no differences in fetal outcome.\n Misoprostol 50 microg was associated with less use of oxytocin in labor, a shorter induction to delivery interval and fewer cesarean sections for failure to progress when compared with extra-amniotic PGF2alpha gel.", "To compare the effectiveness of intravaginal and intracervical prostaglandin E2 (PGE2) gel for cervical ripening, defined as an increase of 3 or greater in the Bishop score, and for induction of labor.\n Women with Bishop score 4 or less were assigned randomly to receive either 2 mg PGE2 intravaginally (n = 125) or 0.5 mg intracervically (n = 122). If the Bishop score was 4 or less, another dose of PGE2 was given after 6 hours, and up to two additional doses were given 6 hours apart on the second day. An oxytocin infusion was begun when the Bishop score was 5 or greater in absence of spontaneous labor, or if labor had not begun on the third day.\n Baseline characteristics of the two groups were similar. Survival analysis showed that time from PGE2 application, to obtain an increase of 3 or greater in the Bishop score, to vaginal delivery was significantly shorter with intravaginal PGE2 (logrank test: P = .003 and < .001 after stratification for parity, respectively). Thirty-one percent of women in the intravaginal gel group required oxytocin for labor induction compared with 63% in the intracervical group (P < .001). There were no significant differences in relation to cesarean delivery rate, Apgar scores at 5 minutes, and arterial umbilical cord pH, although the power of our study was limited to detect differences in proportions of adverse outcomes.\n Vaginal PGE2 gel is more effective than intracervical gel for cervical ripening and labor induction.", "To determine the more applicable of two ways of prostaglandin induction currently in use in second trimester induced abortions for congenital or chromosomal abnormalities.\n A prospective randomised controlled trial.\n Department of Obstetrics and Gynaecology, Tygerberg Hospital, CP.\n Twenty consecutive patients admitted for termination of pregnancy for congenital or chromosomal abnormalities between 14 and 26 weeks' pregnancy duration.\n Patients were randomly selected to receive either 1.5 mg prostaglandin E2 (PGE2) gel extra-amniotically or 25 mg prostaglandin F2 alpha (PGF2 alpha) intra-amniotically. Patients in both groups received oxytocin to a maximum dosage of 120 mU per minute if they had not aborted 18 hours after the original administration of either prostaglandin regimen. If abortion had not taken place 36 hours after commencement of treatment, management was considered unsuccessful.\n Proportion of successful inductions and complications.\n Complications of management were rare and did not differ between the two management groups. However, there were significantly more failures in the group who received intra-amniotic PGF2 alpha (7 v. 2 patients) as well as a significantly higher need for oxytocin in this group (10 v. 4 patients).\n With promising drugs such as prostaglandin analogues and anti-progesterones not universally available, methods of induction suitable to the local situation should be sought. Extra-amniotic PGE2 seems more suitable than intra-amniotic PGF2 alpha because of a shorter induction-to-delivery time without increased morbidity.", "A study was designed to see if incorporating intracervical administration of prostaglandin could affect the outcome of postdate pregnancies. All patients with verified dates, at least 41 6/7 weeks pregnant and enrolled in an antepartum testing schedule were randomized in a double-blind fashion to receive either 0.5 mg of prostaglandin E2 (PGE2) suspended in methylcellulose or a placebo of the gel alone. The gel was inserted directly into the cervical canal after the patient had a reactive/negative contraction stress test. The patient was then observed on an external fetal monitor for an hour before going home. A total of 23 patients received PGE2, and 20 received the placebo. Results were analyzed for the following: change in the Bishop score, lag time from dosage to delivery, spontaneous versus induced labor, cesarean section rate, length of labor and neonatal outcome. There were no significant differences between the groups except in the incidence of patients going into labor within 72 hours. The results indicate that, in general, 0.5 mg of intracervical PGE administered at greater than or equal to 41 6/7 weeks without subsequent oxytocin induction of labor did not appear to significantly alter the obstetric outcome.", "A randomised controlled trial was carried out in 50 primigravidae and 50 multigravidae to compare the effectiveness in induction of labour after low amniotomy of prostaglandin E2, given as an oral solution, and oxytocin, given as buccal tablets. The results showed that in dosages recommended by the manufacturers, both oxytocic preparations were almost equally effective. With oral oxytocin, once labour had been established and dosage was left to the discretion of the staff, there appeared to be a potentially dangerous tendency to continue giving large doses despite adequate uterine contractions. The authors comment that this was probably the reason why oxytocin-treated multigravidae having normal deliveries within 24 hours had labours significantly shorter on average than those of other successfully induced patients.", "To determine whether the use of a prostaglandin (PG) E2 3-mg pessary followed by a delay of 12 hours before stimulation of labor with oxytocin improves obstetric outcome compared with the use of a placebo pessary.\n One hundred fifty-five nulliparas at term with poor cervical scores (modified Bishop score below 6 of 10) and premature rupture of membranes (PROM) were recruited for this double-blind, placebo-controlled randomized trial. On admission to the study, either a PGE2 pessary or an identical-appearing placebo pessary was inserted into the posterior fornix. If labor did not start in the next 12 hours or if symptoms and signs of infection were evident, labor was induced with oxytocin infusion. Assignment was unblinded at the end of the study, and details of the labor and maternal and neonatal outcome in women who received a PG pessary were compared with those who received a placebo pessary.\n Women receiving a PG pessary were significantly less likely to require stimulation of labor at the end of 12 hours than were those given a placebo pessary (37 versus 58%, P = .002). The mean time between admission to study and delivery was significantly shorter in the PG group compared with the placebo group (15 versus 19 hours, P = .01). The rate of cesarean delivery was not statistically different in the two groups (13.9% with PG versus 15.8% with placebo).\n In nulliparas with poor cervical scores who present with PROM at term and no evidence of infection or obstetric complications, use of a PGE2 pessary resulted in more women establishing labor earlier, with a resultant reduction in the admission-to-delivery interval, compared with the use of a placebo pessary. The cesarean delivery rates in the two groups were similar, and there were no significant differences in neonatal outcome.", "Two different applications of prostaglandin E2 for induction of labor were randomly used in 113 women with an unripe cervix; 57 women were given prostaglandin suppositories each containing 2.5 mg PGE2 in a basis of Witepsol S55 (Dynamit Nobel), another 56 women were treated with intracervical gel containing 1 mg PGE2 in 5 g hydroxypropylmethyl cellulose. The treatment was repeated after 4 h if the cervix was still unripe, and the procedure was repeated the following day if the cervix was still unfavorable. Cesarean sections was performed within 48 h after the start of induction and before the second stage of labor in 8 women in the suppository group and 7 women in the intracervical gel group. Of the remaining 98 women, 73% (34/48 women) in the suppository group and 36% (18/50 women) in the cervical gel group had delivered within 24 h (p less than 0.01). After 48 h, 88% (42/48 women) in the suppository group and 74% of the women (37/50 women) in the cervical gel group had delivered (p greater than 0.05). The induction-delivery interval in the suppository group was half that found in the cervical gel group. There was no significant difference between the two groups in the use of instrumental vaginal deliveries and cesarean sections nor was there any difference with regard to fetal distress. The post-delivery condition of the newborn was similar in the two groups. No side-effects were reported in either of the two groups.", "To compare the outcome of induction of labour using a single versus two doses of prostaglandin E2 vaginal gel.\n Prospective randomised trial comparing a single dose of prostaglandin E2 2 mg vaginal gel in the evening with two doses of prostaglandin E2 (2 mg), the second being given after six hours if labour had not started or the cervix was still unripe. Amniotomy and oxytocin titration were performed when necessary for both protocols. Nulliparae and multiparae were analysed separately by treatment intention.\n A maternity unit in a district general hospital annually delivering > 6000 women.\n Nine-hundred and ninety-five women with viable singleton pregnancies and cephalic presentation at term without previous history of caesarean section who were advised to have labour induced with prostaglandins.\n Need for formal amniotomy and oxytocin augmentation, use of epidural analgesia, rate of intrapartum interventions, mode of delivery and neonatal condition at birth.\n For multiparae two prostaglandin doses resulted in a significant reduction in the need for formal amniotomy (15% vs 30%) and oxytocin augmentation (28% vs 38%) compared with those receiving a single dose; there was no significant difference for nulliparae. Other interventions during labour, length of labour, and mode of delivery were similar in both protocols. Failed induction occurred only in nulliparae and was similar in both protocols (1%). There was no discernible difference in fetal or neonatal outcome although passage of meconium was more common in labour if two doses had been given, as was neonatal admission to the special care baby unit.\n There was little clinical benefit from inducing labour with two doses of prostaglandin E2 at a six-hour interval, compared with a single dose. There may be financial advantages with a two-dose regimen.", "In a material of 88 patients with premature rupture of the membranes and unripe cervix, a comparative investigation was undertaken to compare the effects of prostaglandin E2 (PGE2) vaginal tablets and intravenous oxytocin on induction of labour. The patients were subdivided at random into two groups: 42 patients treatment with PGE2 and 46 treatment with intravenous oxytocin. The results did not reveal any significant differences in the numbers of successful inductions regardless of the Bishop score at the commencement of stimulation but the duration of induction was found to be briefer in the oxytocin group. No significant differences were observed in the numbers of instrumental interventions in the two groups nor in the frequencies of side effects and in the employment of analgesics. Treatment with PGE2 vaginal tablets is considered to be more acceptable by the patients and easier for the staff to use. The tablets were just as safe and reliable in use as intravenous oxytocin for induction of labour in cases of premature rupture of the membranes and Bishop scores less than 6, but the duration of induction was significantly longer.", "To compare labour outcome in women who had labour induced with PGF2 alpha gel, PGE2 vaginal pessary or misoprostol administered intravaginally or orally.\n Unmasked randomised controlled trial.\n Department of Obstetrics and Gynaecology, University of Zimbabwe, Harare.\n Women with a singleton foetus in cephalic presentation after 37 weeks gestation admitted for induction of labour who were randomised to prostaglandin F2 alpha gel (n = 76), prostaglandin E2 pessary (n = 75) and misoprostol administered either intra-vaginally (n = 128) or orally (n = 127).\n Primary outcome was induction to delivery interval. Secondary outcomes included use of oxytocin during labour, mode of delivery, duration of labour, neonatal condition at delivery and maternal complications.\n Four hundred and six women admitted for induction of labour with a singleton foetus in cephalic presentation after 37 weeks gestation were enrolled. To estimate the risk with induction using other agents the odds ratio and 95% confidence interval was calculated using the group that received prostaglandin F2 alpha gel as referents.\n The women were comparable for baseline characteristics. Compared to prostaglandin F2 alpha gel, the need for augmentation with oxytocin in labour was significantly reduced in women induced with prostaglandin E2 pessary (OR 0.46; 95%CI 0.23 to 0.93), vaginal misoprostol (OR 0.34; 95%CI 0.18 to 0.63) and oral misoprostol (OR 0.42; 95%CI 0.22 to 0.78). There was no difference in mode of delivery. There was a significantly reduced risk (OR 0.20; 95%CI 0.04 to 0.86) of Caesarean section (CS) for failure to progress in the vaginal misoprostol group. Labour induced with misoprostol and prostaglandin E2 pessary was significantly shorter than in prostaglandin F2 alpha gel. Vaginal misoprostol significantly shortened the induction to delivery interval. There were more admissions to the neonatal unit in the misoprostol groups.\n Compared to prostaglandin F2 alpha gel, misoprostol and prostaglandin E2 pessary had reduced need for oxytocin and a shorter duration of labour. Effects of misoprostol on the foetus need further investigation before it is used as a routine agent for induction of labour.", "We have studied the influence of endocervical application of 0.4 mg prostaglandin E2 (PGE2) in gel on the clinical outcome of pregnancies of at least 36 weeks' duration complicated with premature rupture of the membranes (PROM) and unripe cervix, (modified Bishop score of 7 or less). There were 579 women in the study. The PGE2 gel was applied within the first 12 hours after PROM. The first 60 women were randomly divided into controls given oxytocin infusions and experimental subjects given PGE2 gel. All others were given PGE2 gel, and the results were compared with those obtained in patients with similar criteria who were treated with oxytocin infusions during the preceding year. The clinical outcome was significantly better in the PGE2-treated patients than oxytocin-infused patients. PROM to delivery interval and the incidence of operative deliveries were significantly reduced. No adverse effects on the neonates were observed and the incidence of neonatal infection declined. It is concluded that cervical ripening with PGE2 gel in patients with PROM and unripe cervix near term significantly improves the outcome for both mother and child.", "Two hundred consecutive women with uncomplicated pregnancies, at or within 4 days of their expected date of confinement, were prospectively randomized into 2 groups. One group had expectant management, with twice weekly surveillance tests, while the other group had 3 mg of vaginal prostaglandin E2 as outpatient treatment. There were 104 women in the expectant group and 70 in the induction group (26 women allocated to induction preferred no treatment). The average number of days to delivery was 1.6 in the induction group and 5.2 in the expectant group (p < 0.001). While meconium was much less frequent in the induction group (p < 0.002), all other outcome measures, including cesarean section rates, incidence of macrosomia, and Apgar scores, were similar in the two groups.", "Prostaglandin E2-tablets were compared to intravenous oxytocin for the stimulation of labor in 201 patients at or near term, with premature spontaneous rupture of the membranes without labor activity for 6 hours after the escape of fluid. The patients were randomly allocated; 99 were treated with PGE2-tablets (0.5-1.5 mg/hr) and 102 with intravenous oxytocin (7.5-45 mIU/min). The treatment was ineffective in the PGE2 group in 3 cases; these were treated successfully with intravenous oxytocin. In the oxytocin group, 3 patients were delivered by cesarean section for reasons not associated with the drug. A significant difference was found in the stimulation-delivery time, in favor of intravenous oxytocin. Although PGE2 tablets are a safe and convenient alternative to intravenous oxytocin, the investigation showed that intravenous oxytocin is preferable in cases of premature rupture of the membranes with more than 6 hours without labor activity.", "Prostaglandin E2 is effective for induction of labor but many preparations exist using a variety of vehicles from which the active ingredient may not be equally available. Plasma concentrations of bicyclic PGE2 metabolite (PGEM) and 13, 14-dihydro, 15-keto PGF2 alpha (PGFM) were measured following administration of a 3mg PGE2 vaginal tablet or 1mg PGE2 vaginal gel to twenty-four parous women with favorable induction features, randomly allocated to receive one or other preparation. PGEM increased rapidly following both administration of the 3mg PGE2 vaginal tablet and the 1mg PGE2 vaginal gel, reaching a peak within 40 minutes of PGE2 administration. The maximal rise in PGEM in the gel group correlated directly with the change in cervical score and inversely with the need for augmentation with oxytocin and the induction-delivery interval. A secondary rise in PGFM was noted in both groups 3-4 hours following PGE2 administration. The magnitude of the increase in PGE2 may be important in the clinical response to PGE2 administration, while PGE2 absorption may switch-on endogenous PGF2 alpha production, similar to what is seen in spontaneous labor.", "Sixty-nine patients (48 primigravidae and 21 multigravidae) with 12 hours of spontaneous premature rupture of membranes (PROM) after 36 weeks gestation were randomly allocated to receive either prostaglandin E2 (PGE2) oral tablets or intravenous oxytocin to stimulate labor. The two treatments were compared regarding stimulation - delivery interval (SDI), analgesic requirements, maternal and fetal side effects, and patient acceptability. The mean SDI was shorter in the oxytocin group, but without statistical significance. Analgesic requirements and fetal side effects were similar in the two groups, but there was a higher incidence of nausea and vomiting in those patients receiving the maximum dose (1 mg hourly) of PGE2. On subjective assessment, clinicians considered oxytocin to be more effective (p less than 0.05), while midwives felt both regimes to be equally helpful. PGE2 oral tablets were significantly (p less than 0.05) more acceptable to the patients, who preferred the convenience of oral dosing, the absence of an i.v. line and the increased mobility. It is concluded that PGE2 tablets are a safe and effective method of stimulating labor following PROM, and highly acceptable to parturients. In those women in whom labor has not been established within 8 h of initiating PGE2 therapy, or in whom gastric side effects are troublesome, intravenous oxytocin should be substituted.", "Our purpose was to compare the efficacy of extra-amniotic saline infusion plus high dose oxytocin with prostaglandin E2 intracervical gel (Dinoprostone) for preinduction cervical ripening.\n 166 nulliparous women with term pregnancies, vertex presentation, intact membranes and a Bishop score < or = 4 referred for labor induction were randomly assigned to receive a 0.5 mg PGE2 intracervical gel and extra-amniotic saline infusion (EASI) plus high-dose oxytocin. Changes in the Bishop scores, labor progress, various labor end points and outcomes of labor were assessed. Data were analyzed using chi2 analysis or the Student t-test.\n 151 women were studied after 15 exclusions, 75 were assigned to PGE2, and 76 to EASI. The groups were similar in age, race, indication for induction and gestational age. The EASI group had a significant improvement in Bishop score and greater dilation. The mean time to vaginal delivery was 11.4+/-4.8 hours and 18.9+/-6.4 hours for the EASI and PGE2 groups respectively (P=0.001). The cesarean delivery rate was not significantly different between the two groups (25% for the EASI group; 34.6% for the PGE2 group). The cesarean rate due to failure to progress, fetal labor intolerance, and maternal and neonatal outcomes were similar in the two groups.\n Preinduction cervical ripening with EASI plus high dose oxytocin resulted in greater changes in Bishop score, and shorter time to normal vaginal delivery than with PGE2 gel in nulliparous women, without increasing the cesarean rate due to failure to progress or fetal labor intolerance.", "In a prospective randomized study, 36 patients with spontaneous rupture of the membranes of greater than or equal to 4 h duration were stimulated with 3 mg vaginal prostaglandin E2 pessaries or intravenous oxytocin. Oxytocin stimulation was associated with shorter labours and a lower incidence of abnormal cervimetric progress. Of the patients given prostaglandin pessaries, 40% required a second dose after 4 h for slow progress; 45% of the primigravidae subsequently developed abnormal labour which was corrected by augmentation with oxytocin in all cases. One caesarean section was carried out for disproportion, and the remaining 35 patients were delivered vaginally. Prostaglandin pessaries were not associated with an increased incidence of hyperstimulation or sepsis. In conclusion, although PGE2 pessaries are safe in spontaneous rupture of the membranes, intravenous oxytocin is more efficient in stimulating labour.", "A group of 84 women at 39-43 weeks of pregnancy were randomly allocated to a blind trial of induction of labor with vaginal suppositories containing inert material or either 0.2 mg or 0.4 mg of prostaglandin E2. The suppositories were self-administered every two hours during waking hours on two successive days until labor started or 15 had been used. Side-effects were absent. Labor was established within 48 hr of insertion of the first suppository in 9.3% of control patients, 65.4% of those treated with 0.2 mg PGE2 and 85.7% of those treated with 0.4 mg PGE2. The mean Apgar scores in the three groups were the same. The mean total dose of PGE2 were 2.0 mg (0.2 mg group) and 2.3 mg (0.4 mg group). It is concluded that vaginal PGE2 is an effective and acceptable method of inducing labor at term.", "This randomized clinical trial compared oxytocin induction of labor with expectant care for 48 hours after prelabor rupture of the membranes at term. Women at term with prelabor rupture of the membranes for at least 8 hours were assigned at random to induction with oxytocin or to expectant management for 48 hours followed by induction if necessary. Of 168 eligible women, 123 (73%) agreed to participate. More women in the induction group (23%) than in the expectant group (10%) had operative delivery, either cesarean section or instrumental vaginal delivery. In the induction group 41% received analgesia versus 24% in the expectant group (p < 0.005). There was no difference in the rate of maternal and neonatal infection between groups and sepsis was not observed. The active policy of oxytocin induction exposed the mother to a higher risk of operative delivery and a less comfortable labor than the 48 hours expectant care option.", "To determine which of three methods of cervical ripening resulted in the lowest cesarean rate in women with unfavorable cervices and indications for labor induction.\n Consenting women with singleton gestations, vertex presentations, and unfavorable cervices (dilatation under 2 cm and effacement under 75%) were randomly assigned to laminaria and standard intravenous oxytocin, serial doses of intracervical prostaglandin (PG) E(2) gel (Prepidil, Pharmacia & Upjohn, Inc., Kalamazoo, MI) 0.5 microg every 6 hours for two doses followed by oxytocin if indicated, or extra-amniotic saline infusion and oxytocin.\n An interim analysis after recruitment of 321 subjects, 67% of the planned sample, found similar cesarean rates for the three groups (laminaria 36%; PGE(2) gel 33%; saline infusion 29%; P =.59); however, the mean randomization-to-delivery interval was significantly longer in the PGE(2) group. Stochastic curtailment, as part of the interim analysis, indicated a low likelihood of achieving a statistically significant difference in cesarean rates between PGE(2) gel and the other two groups. Therefore, we completed the study with saline infusion and laminaria. The saline infusion and laminaria groups had similar preinduction characteristics. The cesarean rates were similar (saline infusion 25.4% versus laminaria 30.3%; P =.32), but the mean interval from randomization to delivery was shorter in the saline infusion group (18.0 versus 21.5 hours, P =.002). There were no significant differences in selected maternal and neonatal morbidities.\n Cervical ripening with extra-amniotic saline infusion, PGE(2), or laminaria resulted in comparable cesarean rates in women with an unfavorable cervix and indications for labor induction. Extra-amniotic saline infusion had the shortest randomization-to-delivery interval without increasing maternal or neonatal morbidity.", "Prostaglandin E2 for local application has been widely used for preinduction cervical ripening in cases presenting with an unfavorable cervical state. The optimal way of administering prostaglandin E2, however, remains unclear. The aim of this study was to compare the effect of multiple application of 0.5 mg Minprostin intracervical Gel to the effect of 3 mg Minprostin vaginal tablets in priming the uterine cervix and inducing labor in an open, prospective, randomised study.\n PGE2 was applied up to three times a day for two days until ripening was obtained or labor induced. In case no progress took place amniotomy was performed and i.v. oxytocin stimulation one hour later if necessary. A total of 208 pregnant women, consecutively admitted for induction of delivery, with Bishop Scores 0-5, were included.\n Minprostin gel (group I) and Minprostin tablets (group II) were equally effective in ripening the cervix. Delivery within 48 hours was achieved in 59% and 63% respectively. The mean number of applications was 2.6 (s.d. 1.6) and 2.7 (s.d. 1.3) respectively. In case more than four doses were required no further effect was seen on delivery rates. Rates of cesarean section (performed in 15% and 18% respectively), labor induction (3%/1%), drop outs (14%/12%) and failed inductions (10%/5%) were comparable. Patients in group I had a significantly lower demand for analgesia. A significantly shorter induction-delivery interval in group II was seen in patients with preinduction Bishop scores 3-5 compared to patients with Bishop scores 0-2. Side effects were few. Both procedures appear safe.\n Cervical ripening and induction of delivery by local administration of prostaglandin E2 gel or vaginal tablets in cases presenting with an unfavorable cervical state is equally effective.", "A comparative study of labor induction has been performed on 471 consecutive patients. Primary amniotomy was performed in 227 cases, and 103 of these patients were stimulated, 57 patients with PGE2 tablets and 46 with oxytocin. In the remaining 124 cases labor was induced within 4 hours without medical stimulation. Primary amniotomy was omitted in 244 cases, as the head was not engaged and the cervix was unripe. After random allocation to the treatment groups 125 patients received PGE2 tablets (ProstinR), and 119 patients received oxytocin intravenously. After 2 days of stimulation without primary amniotomy, delivery was induced in 83 per cent of the patients receiving PGE2 and in 84 per cent of the patients receiving oxytocin. All patients on whom primary amniotomy had been performed were delivered on the first day. There was no difference in the success rate between PGE2 and oxytocin treatments in patients with the same Bishop score. The performance of amniotomy at the beginning of induction led to a significantly lower total dose as well as a lower maximal dose of PGE2 and oxytocin. There was no difference in the duration of active labor in patients receiving PGE2 or oxytocin. There were no differences in the incidence of fetal distress and low Apgar scores between the different groups. No serious side effects occurred. Vomiting and diarrhea in 14 patients (8 per cent) receiving PGE2 was in contrast to 3 patients with these symptoms (2 per cent) in the oxytocin group. Oral administration of PGE2 is a convenient, effective and safe alternative to oxytocin for the induction of labor; however, PGE2 was not found superior to oxytocin in cases with a low Bishop score.", "Thirty-eight term pregnant women with a moderately unfavorable cervix (cervical score 4-5 p.) were randomly given intravenous oxytocin (Group A) or 3 mg PGE2 as a vaginal suppository (Group B) for labor induction. Eight out of 19 in Group A and 17 out of 19 in Group B gave birth vaginally within 24 h. The remaining 11 women in Group A had still an unfavorable cervix after 24 h. They were then given 3 mg PGE2 as a vaginal suppository and all but one had given birth vaginally without complications within 24 h. In Group B only 2 were still undelivered after 24 h. Both had a favorable cervix and were delivered vaginally within 12 h after intravenous infusion of oxytocin. The number of instrumental deliveries in Group A was one cesarean section and two vacuum extractions and in Group B three vacuum extractions. One woman in Group B reported nausea and vomiting and in one had strong uterine contractions in the second stage of labor. Otherwise no side effects were registered. All babies were born in good condition with Apgar scores greater than or equal to 7. In conclusion, vaginal application of 3 mg PGE2 as a suppository seems to be more effective than intravenous infusion of oxytocin for labor induction in women with half-ripened cervices, i.e. cervical scores of 4-5 p." ]	Induction of labour using mechanical methods results in similar caesarean section rates as prostaglandins, for a lower risk of hyperstimulation. Mechanical methods do not increase the overall number of women not delivered within 24 hours, however the proportion of multiparous women who did not achieve vaginal delivery within 24 hours was higher when compared with vaginal PGE2. Compared with oxytocin, mechanical methods reduce the risk of caesarean section.
CD004401	[ "8436464", "16968847", "15930204", "9109139", "6816006", "9821420", "17353072", "19434268", "8258205", "11159657", "11433046", "17846935", "8970215", "10819344", "17468653" ]	[ "Prophylaxis for recurrent acute otitis media: a Brazilian study.", "Wait-and-see prescription for the treatment of acute otitis media: a randomized controlled trial.", "Nonsevere acute otitis media: a clinical trial comparing outcomes of watchful waiting versus immediate antibiotic treatment.", "Continuous twice daily or once daily amoxicillin prophylaxis compared with placebo for children with recurrent acute otitis media.", "Penicillin treatment of acute otitis media in children. A study of the duration of treatment.", "A multicenter, randomized, double-blind trial of 5 versus 10 days of antibiotic therapy for acute otitis media in young children.", "Treatment of acute otitis media with probiotics in otitis-prone children-a double-blind, placebo-controlled randomised study.", "Management for the children with otitis media with effusion in the tertiary hospital.", "Is treatment of acute otitis media with once-a-day amoxicillin feasible? Results of a pilot study.", "Pragmatic randomised controlled trial of two prescribing strategies for childhood acute otitis media.", "Reducing antibiotic use in children: a randomized trial in 12 practices.", "Evaluation of phenoxymethylpenicillin treatment of acute otitis media in children aged 2-16.", "Efficacy of antimicrobial prophylaxis for recurrent middle ear effusion.", "Five vs. ten days of antibiotic therapy for acute otitis media in young children.", "Failure of xylitol given three times a day for preventing acute otitis media." ]	[ "We enrolled 60 children with recurrent acute otitis media (AOM) in a study of the effectiveness of antimicrobial prophylaxis. All children were entered into the study following an acute episode of infection treated with amoxicillin (AMX) for 10 days. Following therapy, the children were re-examined, and then randomly assigned to receive either trimethoprim-sulfamethoxazole (TMP-SMX), amoxicillin (AMX) or a placebo (PLA). Twenty children were included in each group. Each drug was administered once a day at bedtime, at 1/3 the therapeutic dose, for 3 months. Children were re-evaluated with pneumootoscopy during episodes of acute illness and with pneumootoscopy and impedance tympanometry (TYMP) at monthly intervals. We observed a significantly increased rate of recurrent AOM in children receiving placebo compared with those who received antibiotics (50% vs. 17% P < 0.005). Both prophylactic antibiotics were equally effective in preventing recurrent AOM (recurrence rate 20% TMP-SMX, 15% AMX). We also observed that recurrences in children receiving placebo occurred earlier in the study period than in those receiving antibiotics. These results suggest that antimicrobial prophylaxis in children with recurrent acute otitis media is effective in reducing subsequent disease. The similar efficacy of both antibiotics tested suggests that the less expensive agent should be used.", "Acute otitis media (AOM) is the most common diagnosis for which antibiotics are prescribed for children. Previous trials that have evaluated a \"wait-and-see prescription\" (WASP) for antibiotics, with which parents are asked not to fill the prescription unless the child either is not better or is worse in 48 hours, have excluded children with severe AOM. None of these trials were conducted in an emergency department.\n To determine whether treatment of AOM using a WASP significantly reduces use of antibiotics compared with a \"standard prescription\" (SP) and to evaluate the effects of this intervention on clinical symptoms and adverse outcomes related to antibiotic use.\n A randomized controlled trial conducted between July 12, 2004, and July 11, 2005. Children with AOM aged 6 months to 12 years seen in an emergency department were randomly assigned to receive either a WASP or an SP. All patients received ibuprofen and otic analgesic drops for use at home. A research assistant, blinded to group assignment, conducted structured phone interviews 4 to 6, 11 to 14, and 30 to 40 days after enrollment to determine outcomes.\n Filling of the antibiotic prescription and clinical course.\n Overall, 283 patients were randomized either to the WASP group (n = 138) or the SP group (n = 145). Substantially more parents in the WASP group did not fill the antibiotic prescription (62% vs 13%; P<.001). There was no statistically significant difference between the groups in the frequency of subsequent fever, otalgia, or unscheduled visits for medical care. Within the WASP group, both fever (relative risk [RR], 2.95; 95% confidence interval [CI], 1.75 - 4.99; P<.001) and otalgia (RR, 1.62; 95% CI, 1.26 - 2.03; P<.001) were associated with filling the prescription.\n The WASP approach substantially reduced unnecessary use of antibiotics in children with AOM seen in an emergency department and may be an alternative to routine use of antimicrobials for treatment of such children.\n clinicaltrials.gov Identifier: NCT00250900.", "The widespread use of antibiotics for treatment of acute otitis media (AOM) has resulted in the emergence of multidrug-resistant pathogens that are difficult to treat. However, it has been shown that most children with nonsevere AOM recover without ABX. The objective of this study was to evaluate the safety, efficacy, acceptability, and costs of a non-ABX intervention for children with nonsevere AOM.\n Children 6 months to 12 years old with AOM were screened by using a novel AOM-severity screening index. Parents of children with nonsevere AOM received an educational intervention, and their children were randomized to receive either immediate antibiotics (ABX; amoxicillin plus symptom medication) or watchful waiting (WW; symptom medication only). The investigators, but not the parents, were blinded to enrollment status. Primary outcomes included parent satisfaction with AOM care, resolution of symptoms, AOM failure/recurrence, and nasopharyngeal carriage of Streptococcus pneumoniae strains resistant to ABX. Secondary outcomes included medication-related adverse events, serious adverse events, unanticipated AOM-related office and emergency department visits and telephone calls, the child's absence from day care or school resulting from AOM, the parent's absence from school or work because of their child's AOM, and costs of treatment. Subjects were defined as failing (days 0-12) or recurring (days 13-30) if they experienced a higher AOM-severity score on reexamination.\n A total of 223 subjects were recruited: 73% were nonwhite, 57% were <2 years old, 47% attended day care, 82% had experienced prior AOM, and 83% had not been fully immunized with heptavalent pneumococcal vaccine. One hundred twelve were randomized to ABX, and 111 were randomized to WW. Ninety-four percent of the subjects were followed to the 30-day end point. Parent satisfaction with AOM care was not different between the 2 treatment groups at either day 12 or 30. Compared with WW, symptom scores on days 1 to 10 resolved faster in subjects treated with immediate ABX. At day 12, among the immediate-ABX group, 69% of tympanic membranes and 25% of tympanograms were normal, compared with 51% of normal tympanic membranes and 10% of normal tympanograms in the WW group. Parents of children in the ABX group gave their children fewer doses of pain medication than did parents of children in the WW group. Subjects in the ABX group experienced 16% fewer failures than subjects in the WW group. Of the children in the WW group, 66% completed the study without needing ABX. Immediate ABX resulted in eradication of S pneumoniae carriage in the majority of children, but S pneumoniae strains cultured from children in the ABX group at day 12 were more likely to be multidrug-resistant than strains from children in the WW group. More ABX-related adverse events were noted in the ABX group, compared with the WW group. No serious AOM-related adverse events were observed in either group. Office and emergency department visits, phone calls, and days of work/school missed were not different between groups. Prescriptions for ABX were reduced by 73% in the WW group compared with the ABX group. Costs of ABX averaged $47.41 per subject in the ABX group and $11.43 in the WW group.\n Sixty-six percent of subjects in the WW group completed the study without ABX. Parent satisfaction was the same between groups regardless of treatment. Compared with WW, immediate ABX treatment was associated with decreased numbers of treatment failures and improved symptom control but increased ABX-related adverse events and a higher percent carriage of multidrug-resistant S pneumoniae strains in the nasopharynx at the day-12 visit. Key factors in implementing a WW strategy were (a) a method to classify AOM severity; (b) parent education; (c) management of AOM symptoms; (d) access to follow-up care; and (e) use of an effective ABX regimen, when needed. When these caveats are observed, WW may be an acceptable alternative to immediate ABX for some children with nonsevere AOM.", "To determine the effectiveness of amoxicillin administered continuously twice daily vs. once daily vs. placebo to prevent new episodes of acute otitis media (AOM).\n Randomized, double blind, placebo-controlled clinical trial at a hospital-based general pediatric clinic and a private pediatric practice, both in Denver, CO.\n One hundred ninety-four children (age 3 months through 6 years) were enrolled with 3 documented AOM episodes within the prior 6 months, without ventilating tubes or associated anatomic defects, immunodeficiency disorders or allergy to penicillin. Thirty-six were noncompliant and were excluded from the study, leaving 158 evaluable subjects.\n The amoxicillin dosage was 20 mg/kg/day either bid or qd. After randomization to placebo twice daily (bid), amoxicillin once daily (qd)/placebo qd or amoxicillin bid, patients were followed monthly and were also seen for upper respiratory infection symptoms during enrollment in the trial. Development of two new AOM episodes terminated the patients from the study.\n Incidence density (ID) measurements were calculated for all study subjects and were stratified by age and season. Overall study subjects in all 3 arms of the trial had 7243 days at risk during which time they developed 56 new AOM episodes for a annual ID of 2.82. There were no significant differences in the IDs between amoxicillin qd vs. bid or amoxicillin (bid or qd) vs. placebo. After stratifying by age and season of enrollment, there were no significant differences in ID rates among the 3 groups. The proportion of subjects remaining otitis-free was 63% for the placebo group, 64% for once daily amoxicillin and 61% for twice daily amoxicillin.\n While once-a-day dosing was equivalent to twice-a-day dosing for amoxicillin prophylaxis, there was no benefit of amoxicillin prophylaxis compared with a placebo control in preventing new AOM episodes. Because of the potential of excessive antibiotic use to promote the acquisition of resistant pneumococci and the lack of effectiveness in this trial, routine use of amoxicillin prophylaxis should be discouraged.", "Two hundred and ninety-seven children, aged 6 months to 7 years, with AOM were treated with penicillin V. One hundred and forty-eight children were given 25 or 50 mg/kg body weight twice a day for 5 days, and 149 children 25 mg/kg body weight twice a day for 10 days. No differences were found in the rate of healing between the 5- and 10-day groups. The larger penicillin dose, which was given to half the 5-day group, did not lead to improved healing. Treatment with penicillin for 5 days instead of 10 does not mean any increased risk of complications such as SOM, relapses, or therapeutic failure. Nor does the risk of a recurrence of otitis increase either. The investigation showed that the treatment of AOM with penicillin for 10 days, which is the rule in Sweden, can be reduced to 5 days with maintained satisfactory healing and without risk of increasing the number of complications.", "All but 2 of the 15 published trials have failed to show a difference in efficacy between short (3 to 5 days) and standard (7 to 10 days) antibiotic regimens for acute otitis media (AOM). These studies involved relatively few patients under 2 years of age, who are at a higher risk for treatment failure.\n In a prospective, comparative, double-blind, randomized, multicenter trial, we compared amoxicillin/clavulanate in 3 divided doses for 10 days with an identical 5-day regimen, followed by a 5-day placebo period.\n Between February 1995 and May 1996, 385 children (mean age, 13.3 months) were enrolled, 194 in the 5-day treatment group and 191 in the 10-day treatment group. In the per protocol analysis, clinical success was obtained on days 12 to 14 after the beginning of treatment (main analysis) in 125 (76.7%) of the 163 children receiving the 5-day regimen and 148 (88.1%) of the 168 receiving the 10-day regimen (P = .006). Clinical success persisted on days 28 to 42 among 57 (40.4%) of the 141 assessable patients in the 5-day group and 64 (46%) of the 139 assessable patients in the 10-day group. (P = .34). Multivariate analysis showed that the 10-day course was statistically superior only among children cared for outside their homes (86.8% vs 70.8%; P = .008).\n When assessed on days 12 to 14 after the outset of treatment, a 5-day regimen is not equivalent to a 10-day regimen among young children with AOM.", "To examine whether probiotics would reduce the occurrence or duration of acute otitis media (AOM), or the nasopharyngeal carriage of otitis pathogens in otitis-prone children.\n During this double-blind, placebo-controlled, randomised, 24-week intervention, 309 otitis-prone children (10 months-6 years) consumed either one probiotic capsule (Lactobacillus rhamnosus GG and LC705, Bifidobacterium breve 99 and Propionibacterium freudenreichii JS) (n=155) or placebo (n=154) daily. Clinical examinations were carried out and nasopharyngeal samples taken three times. Parents recorded the symptoms of upper respiratory infection (URI) in a diary.\n Probiotic treatment did not reduce the occurrence (probiotic vs. placebo: 72% vs. 65%, OR=1.48, 95% CI 0.87-2.52, p=n.s.) or the recurrence ( three) of AOM episodes (18% vs. 17%, OR=1.04, 95% CI 0.55-1.96, p=n.s.). The median duration of AOM episodes was 5.6 (IQR 3.5-9.4) vs. 6.0 (IQR 4.0-10.5) days, respectively (p= n.s.). There was a tendency showing a reduction in the occurrence of recurrent (4 to 6) respiratory infections in the probiotic group (OR for 4 URIs: 0.56, 95%CI 0.31-0.99, p=0.046; OR for 6 URIs: 0.59, 95% CI 0.34 to 1.03, p=n.s.). Probiotics did not affect the carriage of Streptococcus pneumoniae or Haemophilus influenzae, but increased the prevalence of Moraxella catarrhalis (OR=1.79, 95% CI 1.06-3.00, p=0.028).\n Probiotics did not prevent the occurrence of AOM or the nasopharyngeal carriage of otitis pathogens in otitis-prone children. A tendency showing a reduction in recurrent respiratory infections must be confirmed in further studies.", "Recently, new evidence-based recommendations have been introduced for diagnosing and managing otitis media with effusion (OME) in children. However, there are some difficulties to follow the general guidelines in the tertiary hospitals. The purpose is to evaluate the efficiency of antibiotics or antihistamines for treatment of children with OME in the tertiary hospital with a randomized prospective clinical study.\n Eighty-four children with OME who had been diagnosed in the tertiary hospital were randomized to receive 5 different medications for 2 weeks. We prescribed antibiotics (amoxicillin-clavulanate syrup) in Group I (n=16), antibiotics/steroids (prednisolone) in Group II (n=18), antibiotics/antihistamines (ebastine) in Group III (n=15), antibiotics/steroids/antihistamines in Group IV (n=17), and mucolytics (ivy leaf extract) in Group V (n=17) for control. We followed-up children every 2 weeks and evaluated the state of OME at 3 months.\n Thirty six (42.9%) of 84 children were resolved within average 6.9 weeks after the treatments. Thirty-six (42.9%) were treated with ventilation tube insertion and 12 patients (14.3%) were observed. There was no difference in the resolution rates of OME among the five different protocols (P>0.05). There was no difference in the resolution rates among groups who used steroids, antihistamines, steroids and antihistamines, or other medications to manage 42 children with allergies (P>0.05).\n In the tertiary hospital, the cure rate of children with OME was not as high as well-known, and antibiotics or anti-allergic medications were not more effective than control. We may, therefore, need any other guidelines which are different from the previous evidence-based recommendations, including early operation in the tertiary hospitals.", "We report a study of the feasibility of once-a-day amoxicillin to treat acute otitis media (AOM). Seventy-seven children between ages 7 months and 12 years with AOM participated in a double-blind, placebo-controlled trial. Subjects received amoxicillin 40 mg/kg/day for 10 days. They were similar in age, sex, history of ear infections, and presenting symptoms. Group I received one total dose of amoxicillin and two doses of placebo daily. Group II received three divided doses of amoxicillin daily. Parents kept a daily diary of symptoms related to the child's illness and possible medication side effects. Ten children were lost to follow-up. In the remaining 67, pneumatic otoscopy and tympanometry after 10 to 14 days revealed that AOM had resolved in 82% of group I and 68% of group II. Groups showed no significant differences in persistence of middle ear effusion; 39% in group I and 24% in group II still had fluid. Diaries showed no significant differences between groups in medication side effects. Thus, reduced-frequency dosing for AOM seems feasible and more realistic than current regimens.", "To compare immediate with delayed prescribing of antibiotics for acute otitis media.\n Open randomised controlled trial. Setting: General practices in south west England.\n 315 children aged between 6 months and 10 years presenting with acute otitis media.\n Two treatment strategies, supported by standardised advice sheets-immediate antibiotics or delayed antibiotics (antibiotic prescription to be collected at parents' discretion after 72 hours if child still not improving).\n Symptom resolution, absence from school or nursery, paracetamol consumption.\n On average, symptoms resolved after 3 days. Children prescribed antibiotics immediately had shorter illness (-1.1 days (95% confidence interval -0.54 to -1.48)), fewer nights disturbed (-0.72 (-0.30 to -1.13)), and slightly less paracetamol consumption (-0.52 spoons/day (-0.26 to -0.79)). There was no difference in school absence or pain or distress scores since benefits of antibiotics occurred mainly after the first 24 hours-when distress was less severe. Parents of 36/150 of the children given delayed prescriptions used antibiotics, and 77% were very satisfied. Fewer children in the delayed group had diarrhoea (14/150 (9%) v 25/135 (19%), chi(2)=5.2, P=0.02). Fewer parents in the delayed group believed in the effectiveness of antibiotics and in the need to see the doctor with future episodes.\n Immediate antibiotic prescription provided symptomatic benefit mainly after first 24 hours, when symptoms were already resolving. For children who are not very unwell systemically, a wait and see approach seems feasible and acceptable to parents and should substantially reduce the use of antibiotics for acute otitis media.", "To test whether an educational outreach intervention for families and physicians, based on the Centers for Disease Control and Prevention (CDC) principles of judicious antibiotic use, decreases antimicrobial drug prescribing for children younger than 6 years old. Setting. Twelve practices affiliated with 2 managed care organizations (MCOs) in eastern Massachusetts and northwest Washington State. Patients. All enrolled children younger than 6 years old.\n Practices stratified by MCO and size were randomized to intervention or control groups. The intervention included 2 meetings of the practice with a physician peer leader, using CDC-endorsed summaries of judicious prescribing recommendations; feedback on previous prescribing rates were also provided. Parents were mailed a CDC brochure on antibiotic use, and supporting materials were displayed in waiting rooms. Automated enrollment, ambulatory visit, and pharmacy claims were used to determine rates of antibiotic courses dispensed (antibiotics/person-year) during baseline (1996-1997) and intervention (1997-1998) years. The primary analysis (for children 3 to <36 months and 36 to <72 months) assessed the impact of the intervention among children during the intervention year, controlling for covariates including patient age and baseline prescription rate. Confirmatory analyses at the practice level were also performed.\n The practices cared for 14 468 and 13 460 children in the 2 study years, respectively; 8815 children contributed data in both years. Sixty-two percent of antibiotic courses were dispensed for otitis media, 6.5% for pharyngitis, 6.3% for sinusitis, and 9.2% for colds and bronchitis. Antibiotic dispensing for children 3 to <36 months old decreased 0.41 antibiotics per person-year (18.6%) in intervention compared with 0.33 (11.5%) in control practices. Among children 36 to <72 months old, the rate decreased by 0.21 antibiotics per person-year (15%) in intervention and 0.17 (9.8%) in control practices. Multivariate analysis showed an adjusted intervention effect of 16% in the younger and 12% in the older age groups. The direction and approximate magnitude of effect were confirmed in practice-level analyses.\n A limited simultaneous educational outreach intervention for parents and providers reduced antibiotic use among children in primary care practices, even in the setting of substantial secular trends toward decreased prescribing. Future efforts to promote judicious prescribing should continue to build on growing public awareness of antibiotic overuse.", "To study the clinical recovery from acute otitis media (AOM) in children, 2-16 years of age, managed with or without treatment with phenoxymethylpenicillin (PcV).\n An open, prospective randomized trial. Children aged between 2 and 16 years, presenting with one- or double-sided AOM (without perforation) with symptom duration of less than four days, were included. The children were randomized to PcV for five days or to no primary antibiotic treatment. A health score and compliance were registered on a daily basis for seven days.\n A total of 32 health centres and 72 GPs in south-east Sweden. Subjects. Children aged 2-16 presenting with earache.\n Recovery time, symptom duration, frequency of complications (up to three months) and consumption of healthcare services independent of treatment with or without antibiotics.\n A total of 179 patients carried out the trial; 92 were randomized to PcV, 87 to no primary antibiotic treatment. The median recovery time was four days in both groups. Patients who received PcV had less pain (p <0.001) and used fewer analgesics. There were no significant differences in the number of middle-ear effusions or perforations at the final control after three months. Children randomized to PcV treatment consulted less (p <0.001) during the first seven days.\n Our investigation supports that PcV treatment of AOM does not affect the recovery time or complication rates. PcV provided some symptomatic benefit in the treatment of AOM in otherwise healthy children, aged 2-16 years.", "This trial compared the efficacy of amoxicillin prophylaxis with that of placebo for the management of recurrent middle ear effusion (MEE) in children.\n Children between 7 months and 12 years of age who were effusion-free at entry but had histories of chronic or recurrent MEE were randomly assigned to receive either amoxicillin (20 mg/kg once daily) or placebo for 1 year. They were examined monthly and when there were symptoms of ear, nose or throat disease. Acute otitis media (AOM) and new episodes of otitis media with effusion (OME) were treated with amoxicillin-clavulanate; tympanocentesis was performed when possible for episodes of AOM. Throat cultures were obtained at entry; 4, 8 and 12 months after entry; and with new episodes of AOM and OME. Tympanometry was performed at each visit and audiometry was performed at entry and 4, 8 and 12 months after entry.\n One hundred eleven children were entered in this study. The rates per person year of new episodes of disease in the amoxicillin and placebo groups, respectively, were: MEE, 1.81 vs. 3.18 (P < 0.001); AOM, 0.28 vs. 1.04 (P < 0.001); and OME, 1.53 vs. 2.15 (P = 0.016). Subjects in the amoxicillin group had less time with MEE than the placebo group (19.7 and 33.2%, respectively; P = 0.002). Middle ear and throat cultures did not reveal any increase in beta-lactamase-producing organisms or in Streptococcus pneumoniae attributable to daily use of amoxicillin.\n Amoxicillin prophylaxis lowered the rates of occurrence of MEE, AOM and OME and decreased the percentage of time with MEE. However, because of present day concerns regarding antibiotic resistance, management should be individualized.", "Many publications in recent years have argued in favor of shortened therapy for acute otitis media. However, doubt persists regarding children younger than 2 years, and some authors therefore restrict short course therapy to children older than 2 years.\n In a prospective, comparative, double blind, randomized, multicenter trial we compared cefpodoxime-proxetil, 8 mg/kg/day in two divided doses for 10 days, with an identical 5-day regimen followed by a 5-day placebo period.\n Between October, 1996, and April, 1997, 450 children (mean age, 14.3 months) were enrolled, 227 in the 5-day group and 223 in the 10-day group. In the per protocol analysis clinical success was obtained on Days 12 to 14 after the beginning of treatment (main analysis) in 175 (84.1%) of the 208 children receiving the 5-day regimen and 194 (92.4%) of the 210 children receiving the 10-day regimen (P = 0.009). The superiority of the standard regimen was more marked among children cared for outside their homes (92.5% vs. 81.5%). Clinical success persisted on Days 28 to 42 among 134 (85.4%) of the 157 assessable patients in the 5-day group and 144 (83.7%) of the 172 assessable patients in the 10-day group (P = 0.68).\n The 10-day regimen resulted in a higher success rate at the conclusion of therapy, but there were no differences between the two study groups 4 to 6 weeks after enrollment in the study protocol.", "Xylitol administered regularly 5 times a day after each meal is successful in preventing acute otitis media (AOM) in children, but if given only during respiratory infections it is ineffective against AOM. To find a more convenient dosing regimen, we tested whether xylitol administered 3 times a day reduces the occurrence of AOM.\n In this 3-month randomized, double-blind trial, 663 healthy day care children were randomized to receive either a control product (n = 331) or xylitol (n = 332). Xylitol was given in chewing gum or in a mixture 3 times a day, the daily dose being 0.5 g in the control group and 9.6 g in the xylitol group. The occurrence of the first AOM diagnosed during any period of respiratory symptoms during the follow-up was the main outcome measure.\n At least one AOM episode was diagnosed in 98 of the 331 children who received control products (30%) and in 94 of the 332 who received xylitol products (28%). A total of 142 episodes of AOM were diagnosed in the control group compared with 156 in the xylitol group. The differences were not statistically significant.\n Xylitol given regularly 3 times a day for 3 months during the respiratory infection season failed to prevent AOM." ]	For children at risk, antibiotics given once or twice daily will reduce the probability of AOM while the child is on treatment. In similar populations, antibiotics will reduce the number of episodes of AOM per year from around three to around 1.5. We believe that larger absolute benefits are likely in high-risk children. These conclusions were not affected by sensitivity analyses.
CD000451	[ "9442160", "12118640", "8217970", "1637758", "9442159", "10828706", "10410476", "8649700", "9790365", "2216203", "9509948", "10642965", "8677083", "12521500", "894653", "9662313", "8735733", "8238131", "2213744" ]	[ "Sweeping of the membranes at 39 weeks in nulliparous women: a randomised controlled trial.", "Does sweeping of membranes beyond 40 weeks reduce the need for formal induction of labour?", "Sweeping the membranes: a valid procedure in stimulating the onset of labour?", "Sweeping of the membranes is an effective method of induction of labour in prolonged pregnancy: a report of a randomized trial.", "Does sweeping of the membranes reduce the need for formal induction of labour? A randomised controlled trial.", "Sweeping of the membranes versus uterine stimulation by oxytocin in nulliparous women. A randomized controlled trial.", "A comparative study of membrane stripping and nonstripping for induction of labor in uncomplicated term pregnancy.", "Stripping of membranes as a safe method to reduce prolonged pregnancies.", "Can we decrease postdatism in women with an unfavorable cervix and a negative fetal fibronectin test result at term by serial membrane sweeping?", "Stripping membranes at term: can it safely reduce the incidence of post-term pregnancies?", "Safety and efficacy of stripping of membranes at term.", "Membrane sweeping versus dinoprostone vaginal insert in the management of pregnancies beyond 41 weeks with an unfavorable cervix.", "A randomized controlled trial of membrane stripping at term to promote labor.", "The role of membrane stripping in prevention of post-term pregnancy: a randomised clinical trial in Ile-lfe, Nigeria.", "Membrane stripping to induce labor.", "Management of pregnancies beyond forty-one weeks' gestation with an unfavorable cervix.", "Stretching of the cervix and stripping of the membranes at term: a randomised controlled study.", "Induction versus expectant management in premature rupture of the membranes with mature amniotic fluid at 32 to 36 weeks: a randomized trial.", "Stripping the fetal membranes at term. Is the procedure safe and efficacious?" ]	[ "To determine whether weekly sweeping of the membranes from 39 weeks of gestation results in a reduction in the number of women reaching 41 completed weeks and subsequently in a reduction of the number of women who will need induction of labour.\n Randomised controlled trial.\n Two hundred and seventy-eight nulliparous women, who were seen at the antenatal clinic of a university teaching hospital, were randomly allocated at 39 weeks of gestation to receive on a weekly basis either sweeping of the membranes (n = 140) or a routine pelvic examination (n = 138).\n The time interval between randomisation and delivery, the incidence of prolonged pregnancy (i.e. > 41 completed weeks), and the incidence of induction of labour.\n In 24 women (17%) sweeping of the membranes was not possible. Fifty-three women (38%) in the sweeping group and 50 women (36%) in the control group were delivered within one week after randomisation. Women allocated to sweeping showed a trend towards having a shorter randomisation-delivery interval: 9.4 days versus 10.6 days in the controls (P = 0.087). Sweeping had no statistically significant effect on the mean duration of pregnancy (282.8 days in the sweeping group versus 283.8 days in the control group, P = 0.127). The need for induction of labour was significantly reduced in those women who underwent sweeping (11% versus 26%, P = 0.004), merely as a result of a decrease in the number of women that exceeded 41 weeks (19% versus 33%, P = 0.016).\n Sweeping of the membranes weekly from 39 weeks does not increase the number of women who will deliver within the first week but significantly decreases the number that will reach 41 weeks. Induction of labour then becomes less necessary.", "To assess the efficacy of sweeping of membranes beyond 40 weeks of gestation in reducing the incidence of induction of labour, when induction was planned at 42 weeks.\n Prospective randomised controlled trial.\n A regional obstetric unit in Hong Kong.\n A total of 120 women with certain gestational age, determined by early pregnancy ultrasound scan, were recruited from 1st July, 1998 to 31st December, 1999. Sixty women were randomly allocated to sweeping of membranes and the other 60 women acted as control. The satisfaction for women allocated to sweeping of membranes was assessed by a questionnaire after the procedure. The two groups were assessed on intention-to-treat basis.\n The incidence of formal induction of labour was compared between the two groups. Possible complications of sweeping of membranes such as rupture of membranes, intrapartum infection, postpartum infection, and neonatal infection were also assessed. Maternal and perinatal outcomes were also assessed.\n The recruitment to delivery interval was significantly shorter among women who had sweeping of membranes (3.2 versus 4.2 days, P < 0.05). The incidence of induction of labour was comparable (35.5% versus 38%, RR 0.91, 95% CI 0.57 - 1.46). The incidences of caesarean section and assisted vaginal delivery were comparable. The incidences of premature rupture of membranes, intrapartum, and postpartum infection were comparable. The perinatal outcomes were also comparable between the two groups. Up to 70% of women found that this procedure was associated with significant discomfort. One third of these women complained of significant pain.\n Sweeping of membranes beyond 40 weeks does not reduce the need for formal induction of labour at 42 weeks. Although it is safe, the majority of women felt uncomfortable during the procedure.", "To determine whether sweeping the membranes in pregnancies of longer than 40 weeks gestation results in an accelerated onset of labour and a reduction in the incidence of induction of labour.\n A prospective randomised controlled study.\n The antenatal clinic of a district general hospital.\n One hundred and ninety-five antenatal women with pregnancies proceeding beyond 40 weeks gestation.\n A Bishop score assessment of the cervix alone or combined with a membrane sweep, on a randomised basis.\n Subsequent duration of pregnancy to the onset of spontaneous labour. The incidence of induction of labour for post-maturity.\n Sweeping the membranes significantly reduces the subsequent duration of pregnancy, from an average of five days to two days following the procedure. The proportion of inductions of labour was 8.1% in the swept group and 18.8% in the control group. No harmful side effects to the procedure were noted.\n Sweeping the membranes is a safe and useful procedure which results in a reduced incidence of post-mature pregnancies, and a subsequent reduction in the labour induction rate.", "To determine whether sweeping of the membranes is an effective method of induction of labour in women with prolonged pregnancy.\n Randomized controlled trial.\n A district maternity hospital.\n 65 women attending an antenatal clinic; 33 randomized to sweeping of the membranes and 32 to a control group.\n Proportion of women achieving spontaneous labour.\n Spontaneous labour occurred more often in the sweeping of the membranes group than in the control group (25/33 (76%) vs 12/32 (38%); odds ratio (OR) 4.65; 95% confidence interval (CI) 1.75 to 12.31; P = 0.002). In addition a greater proportion of women in the sweeping group had a cervical dilatation of 4 cm or more at the first vaginal examination in the labour ward (16/33 (49%) vs 5/32 (16%); OR 4.39; 95% CI 1.56 to 12.32; P = 0.005). There were fewer maternal infections in the sweeping group (0/33 vs 4/32 (12%); OR 0.12; 95% CI 0.02 to 0.88; P = 0.04). There were no differences in the type of analgesia used in labour, the mode of delivery or neonatal outcome.\n Sweeping of the membranes is an effective method of induction of labour in women with prolonged pregnancy.", "1. To evaluate the effectiveness of sweeping of the membranes to reduce the need for a formal induction of labour; 2. to evaluate the side effects of this intervention.\n A randomised controlled clinical trial.\n Three tertiary care hospitals of the province of Quebec, Canada.\n Two hundred women for whom non-urgent induction of labour was medically indicated.\n Women were randomly allocated to sweeping of membranes, or vaginal examination for Bishop scoring only.\n 1. Cumulative incidence and relative risk of induction of labour by either oxytocin, prostaglandins or amniotomy; 2. women's discomfort and side effects attributable to sweeping of the membranes.\n Women allocated to sweeping of the membranes required formal induction of labour less frequently than women in the control group, but this difference was not statistically significant (49% vs 60%, RR 0.83, 95% CI 0.64-1.07). Pain during vaginal examination and other side effects were more frequently reported by women allocated to the sweeping group.\n The observed reduction in the need for formal induction of labour is smaller than in previous studies. Side effects and discomfort associated with sweeping of the membranes must be taken into account when counselling women who require induction of labour.", "The aim of this study was to evaluate whether sweeping of the membranes at term could shorten the length of pregnancy and reduce the incidence of postterm pregnancies. We randomly selected 104 nulliparas with uncomplicated pregnancy and gestational age between 281 and 287 days. Our patients were divided into three groups. Group A consisted of 34 women who were subjected to sweeping of the membranes. Uterine stimulation with oxytocin was applied in 35 women (group B), and 35 women (group C) were used as a control group. We had no significant reduction of the time interval from sweeping of the membranes until delivery (1.9 +/- 1.2 days), compared to that of group B (2.1 +/- 0.8 days) as well as that of the control group (2.5 +/- 0.9 days). The incidence of spontaneous labor in patients after sweeping of the membranes was greater (67.6%) when compared with oxytocin-stimulated patients and the control group (p < 0.05). Furthermore, a better Bishop score was noted in patients of group A. No statistically significant difference was noted in the mode of delivery between the groups, but sweeping of the membranes significantly decreased the incidence of postterm pregnancies (p < 0. 05). We concluded that sweeping of the membranes is an effective method for initiating labor in women with a gestational age between 40 and 41 weeks, thus reducing the need for induction.\n Copyright 2000 S. Karger AG, Basel", "A prospective, randomized controlled trial was undertaken at the Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn Hospital to determine whether stripping of the fetal membranes is a safe and effective method for induction of labor in uncomplicated term pregnancy. Ninety-six women were included in this study; 16 were excluded; 41 were randomized to a study group and 39 to a control group. Both groups had pelvic examination performed under sterile technique and a Bishop score was assessed. In the study group, membrane stripping was performed. Gentle pelvic examination for Bishop scoring was continued weekly in both groups. Thirty five of 41 women (85.4%) in the study group delivered within 7 days as compared to 22 of 39 women (56.4%) in the control group, a statistically significant difference (P = 0.004). A statistically significant difference was also observed with respect to the mean number of days to delivery (5.3 +/- 4.9 versus 9.5 +/- 5.9 days, respectively; P = 0.002). No statistically significant differences were observed in both maternal and fetal complications. In conclusion, membrane stripping is a safe and effective method for induction of labor in uncomplicated term pregnancy.", "To evaluate weekly stripping of membranes at term to determine its safety and effectiveness in reducing the incidence of prolonged and postterm pregnancies.\n One hundred forty-two pregnant women with certain gestational dates were randomly selected to receive, starting at 38 weeks, either weekly stripping of membranes (73 patients) or weekly gentle cervical examinations (69 patients).\n Women who received stripping had earlier delivery (8.2 versus 12.2 days; P < .005) and less incidence of delivery at 41 weeks or greater (three versus 13 patients; P < .01). The reduction remained consistent for favorable and unfavorable Bishop scores, and for nulliparas and multiparas. Only three subjects in the study delivered at 42 weeks or greater. No woman reported rupture of membranes after stripping.\n Stripping of membranes is a safe method to reduce the incidence of prolonged pregnancies and the length of term gestations. Larger trials on populations with a higher incidence of postterm pregnancies are needed to evaluate its efficacy in reducing the incidence of postterm pregnancies.", "Our purpose was to determine whether the risk for postdatism can be reduced by serial membrane sweeping in women with an unfavorable cervix at 39 weeks' gestation and a negative fetal fibronectin test result.\n Women with uncomplicated pregnancies, who were candidates for a vaginal delivery with an unfavorable cervix at 39 weeks' gestation and a negative fetal fibronectin test result were asked to participate in this investigation. Patients were chosen at random and assigned to a group for membrane sweeping every 3 days or to a control group who received gentle examinations every 3 days.\n Sixty-five women were selected at random for serial membrane sweeping (n = 33) or for the control group (n = 32). Although gestational age and Bishop score at study entry were similar, the gestational age on admission for delivery was earlier in the membrane sweeping group (39.9 +/- 0.3) versus the control group (41.5 +/- 0.6, P < .0001). The Bishop score on admission to labor and delivery was greater (8.8 +/- 2.1) in the membrane sweeping group than in the control group (6.2 +/- 2.7, P < .0001). The number of women admitted for labor inductions at 42 weeks' gestation was 18 of 32 (56%) in the control group versus none (0 of 24) in the membrane-sweeping group (P < .0001).\n Women with an unfavorable cervix at 39 weeks' gestation and a negative fetal fibronectin test result are at risk for not being delivered by 41 completed weeks and thus may require postdates induction or antenatal testing. Serial membrane sweeping significantly reduces the risk of postdatism and induction of labor.", "Membrane stripping has been used clinically for many years but has not been well studied. An investigation was undertaken to determine whether weekly membrane stripping beginning at 38 weeks could safely reduce post-term pregnancies. One hundred eighty patients with firm gestational dates were randomized to either a treatment or control group. Control subjects received a gentle cervicovaginal examination each week to assess Bishop scores, whereas the treatment group also underwent weekly stripping of membranes. Women who received treatment had earlier delivery (mean +/- SEM 8.60 +/- 0.74 versus 15.14 +/- 0.83 days; P less than .0001) and fewer post-term deliveries than those in the control group (three versus 14; P less than .004). The reduction of post-term pregnancies was most notable in nulliparous women with unfavorable Bishop scores. Complications were similar in both groups. Membrane stripping was safe and was associated with earlier delivery and a decreased incidence of post-term gestation.", "To assess the efficacy of stripping of membranes in initiation of labor and to study its effect on maternal and perinatal morbidity.\n One-hundred primigravidae with certain gestational dates were randomized at 38 weeks gestation to either receive stripping of membranes or only gentle cervical examination. Cervical swabs were taken before pelvic examination at 38 weeks and again at the onset of labor. Placental membranes were sent for bacteriological study after delivery in all patients.\n The mean gestational age, parity and Bishop score were similar in both groups at recruitment. Gestational age at delivery was lower in the study group (38.70 +/- 0.63) compared to the control group. Seventy-two percent of the study group and 8% of the control group had spontaneous onset of labor within 7 days of examination. Labor was induced in one patient (2%) of the study group and 16 patients (32%) of the control group. No statistically significant difference was noted in incidence of premature rupture of membranes (PROM), mode of delivery, intrapartum events and perinatal outcome. No increase in neonatal morbidity was seen in association with this procedure. No patient in the study group had clinical evidence of chorioamnionitis. There was no statistically significant difference in the microbiological flora of both groups.\n Stripping of the fetal membranes is a safe and efficacious procedure for induction of labor. It decreases the incidence of induction of labor with no increase in incidence of maternal and neonatal morbidity.", "To determine the best method of cervical ripening to prevent postdate inductions in women with an unfavorable cervix at 41 weeks' gestation.\n Women presenting at 41 weeks' gestation with a Bishop score of < or = 4 received daily dinoprostone (Cervidil) vaginal inserts (group I) or daily membrane sweeping (group II).\n One-hundred and eighty-two women were prospectively randomized with 91 women in each arm. The women in group II, membrane sweeping, had Bishop scores significantly greater on admission for delivery (p < 0.001), had less time elapsed from admission to delivery (p = 0.018), and had fewer labor inductions at 42 weeks (p = 0.04) than the women in group I, the dinoprostone group. In addition, a greater number of women in group II were admitted in spontaneous labor (p = 0.006) than in group I. Total antenatal costs for the membrane sweeping group was $15,120 versus $59,540 for the dinoprostone group.\n Daily membrane sweeping was more effective than dinoprostone administration with fewer postdate inductions at one-fourth the cost.", "To determine the effectiveness of membrane stripping at term to promote the onset of labor.\n One hundred twenty gravidas at 38 weeks' gestation, who were attending an antenatal clinic and planned to deliver at Maharaj Nakorn Chiang Mai University Hospital in northern Thailand, were assigned randomly to one of two groups. One group had weekly pelvic examinations only, and the other also had membrane stripping, beginning at 38 weeks' gestation and continuing until the onset of labor or until 42 completed weeks' gestation. Outcome measures included the proportion of patients who delivered with 7 days after the first examination, Bishop scores among those who did not deliver, days from the first examination to delivery, incidence of postterm pregnancy, and maternal and fetal complication.\n Twenty-five of 61 patients (41%) assigned to membrane stripping delivered within 1 week, compared with 12 of 59 controls (20.3%), a statistically significant difference (P = .014). There was also a statistically significant difference (P = .013, Mann-Whitney U test) in the Bishop scores among those who did not deliver within 1 week (4 +/- 2.5 versus 2.6 +/- 1.7 in the study and control groups, respectively). A significant difference was also observed with respect to the mean number of days to delivery (8.8 +/- 6.7 versus 13.6 +/- 7.5, respectively; P < .001). The incidence of postterm pregnancy was one of 61 (1.6%) and three of 59 (5.1%) in the stripping and control groups, respectively. No significant differences were observed in maternal and fetal complications.\n Membrane stripping is safe and effective in promoting the onset of labor at term.", "This study was carried out to evaluate the efficacy and safety of membrane stripping at term in reducing the incidence of post-term (41 weeks or greater) pregnancies. One hundred and thirty-seven pregnant women at 38 weeks gestation were randomised to receive either membrane stripping (69) or gentle cervical examination (68). Women who received stripping had earlier delivery (4.8 vs. 12.1 days; P<0.001) and less incidence of delivery at 41 weeks or greater (3% vs. 16%; P=0.009). No statistically significant difference was noted in incidence of premature rupture of membranes, clinical evidence of chorioamnionitis, intrapartum characteristics and perinatal outcome. We conclude that membrane stripping is a safe method to reduce the incidence of post-term pregnancy.", "A group of 91 pregnant women at term were studied randomly to see the effect of digital stripping of the membranes from the lower uterine segment upon the onset of labor. The women with unfavorable cervices (Bishop score 0 to 5) demonstrated a significant increase in the onset of labor within 48 hours as compared to controls. When the cervix was favorable (Bishop score 6 to 10), there was no significant effect. The overall success rate for induction of labor was not significantly altered (43.5% in membrane-stripped patients, 22.2% in controls). There were no major complications of the procedure.", "Our purpose was to determine the optimal management of pregnancies beyond 41 weeks' gestation with a cervix unfavorable for induction.\n All uncomplicated pregnancies that reached 41 weeks' gestation with a Bishop score of < or = 4 were randomly assigned to one of three groups: (1) daily cervical examinations, (2) daily membrane stripping, or (3) daily placement of prostaglandin gel until 42 weeks.\n In 105 pregnancies the Bishop score on admission to labor and delivery was significantly greater in the groups receiving prostaglandin or stripping of the membranes versus the control group, whereas the converse was time of gestational age at delivery (p = 0.0001). Fewer patients required induction in the two treatment groups (20%, 17%) versus the control (69%) patients (p < 0.0001).\n Daily membrane stripping or daily placement of prostaglandin gel is successful in reducing the number of inductions at 42 weeks for postdatism.", "To determine whether routine antepartum stretching of the cervix and stripping of the membranes at term would shorten the length of pregnancies, and whether this correlated with cervical status and fetal and maternal parameters.\n A prospective, randomised, controlled study of 293 term gravidas, free of medical complications, divided into two groups: stretching/stripping, and non-stretching/stripping. Digital separation of the fetal membranes from the lower uterine segment, and cervical stretching, were performed during routine vaginal examination of the first group. In the second group, only routine vaginal examination was performed.\n Of 293 patients, 152 underwent a trial of stretching and stripping; 141 served as a control group. The mean interval (hours to delivery after the procedure) was 136 h (S.D. 10), compared to 161 h (S.D. 11) in the control group (P = 0.095; not significant), but with only a trend towards the shorter interval in the first group. When patients were matched according to weeks of gestation and fetal and maternal parameters, only those at 41 weeks' gestation or more had a significant reduction in the interval from the procedure to delivery (mean 91 h (S.D. 8) compared to mean 125 h (S.D. 10) in the control group; P < 0.007). This observation was independent of cervical status and other maternal or fetal parameters.\n Only patients > or = 41 weeks' gestation benefitted from stretching of the cervix and stripping of the fetal membranes. The effect was not dependent on the cervical status or other maternal and fetal parameters.", "Our objective was to compare maternal and perinatal outcomes between two management schemes for women with preterm premature rupture of the membranes and documented fetal pulmonary maturity.\n Of 164 women with preterm premature rupture of the membranes at 32 weeks to 36 weeks 6 days' gestation, 93 eligible and consenting women were randomly selected for either induction of labor (n = 46) or expectant management (n = 47). Expectant management included hospitalization, assessment for fetal heart rate abnormalities, chorioamnionitis, and labor. Digital cervical examinations were prohibited until progressive labor occurred. Follow-up was also done for the 71 women who did not participate.\n The women in the induction of labor and expectant management groups had similar demographic characteristics and gestational ages (34.1 vs 34.3 weeks). Expectant management was associated with prolonged latencies to labor, delivery, and maternal hospitalization (p < 0.001), as well as increased hospitalization of infants at 2 to 5 days after delivery (p < 0.05). These patients had increased chorioamnionitis and fetal heart rate abnormalities before labor (p = 0.01, 0.03). Infants received more frequent (p < 0.001) and prolonged antimicrobial therapy after expectant management (p = 0.003) with no reduction in proven sepsis (6.8% vs 4.4%). These latter differences were influenced by the neonatologist's concern over potential neonatal infection.\n Among women with preterm premature rupture of the membranes at 32 to 36 weeks with mature surfactant profiles, immediate induction of labor reduces the duration of hospitalization and infection in both mothers and neonates.", "A prospective, randomized investigation was undertaken in a low-risk group of pregnant women at term (38-42 weeks' gestation) to determine if stripping the fetal membranes would safely result in earlier delivery. Ninety-nine patients entered the study; 51 underwent stripping of the membranes, and 48 controls did not. Fifty-nine percent of the patients in the stripped group delivered within one week as compared to 21% in the nonstripped group (P less than .0003). Two pregnancies in the stripped group advanced beyond 42 weeks' gestation as compared to six pregnancies in the control group (P = .12). A single gravida in the control group developed chorioamnionitis during labor. There were no other infections or other complications. Stripping the membranes was associated with earlier delivery and was not associated with any complications." ]	Routine use of sweeping of membranes from 38 weeks of pregnancy onwards does not seem to produce clinically important benefits. When used as a means for induction of labour, the reduction in the use of more formal methods of induction needs to be balanced against women's discomfort and other adverse effects. [Note: The 11 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]
CD006623	[ "20096223", "12645704", "11446941", "11973192" ]	[ "Optimizing the surgical field in pediatric functional endoscopic sinus surgery: a new evidence-based approach.", "Comparative effects of propofol versus fentanyl on cerebral oxygenation state during normothermic cardiopulmonary bypass and postoperative cognitive dysfunction.", "[The effect of encephalogram bispectral index monitoring during total intravenous anesthesia with propofol in outpatient surgery].", "Target-controlled versus manually-controlled infusion of propofol for direct laryngoscopy and bronchoscopy." ]	[ "To conduct the first prospective randomized controlled study 1) evaluating the possibility of improving the quality of the operative field and to provide a bloodless functional endoscopic sinus surgery (FESS) in children through total intravenous anesthesia (TIVA) using remifentanil combined with propofol, and 2) testing the safety and efficacy of remifentanil in propofol-TIVA in inducing controlled hypotension in children at a target mean arterial blood pressure of 50 mm Hg.\n Randomized controlled trial.\n General hospital.\n Seventy children underwent FESS under hypotensive general anesthesia with equal randomization into two groups. Group I received TIVA with remifentanil, whereas group II had balanced anesthesia (BA) with esmolol. Heart rate, blood pressure, operative time, blood loss, and quality of the surgical conditions were recorded.\n Intraoperative blood loss in the TIVA group was less than in the BA group. The quality and dryness of the surgical field in both the visual analogue scale and the six-point scale was significantly better in the TIVA group than in the BA group. Hypotension was sustained at the target mean arterial blood pressure of 50 mm Hg in the two groups, without any significant difference.\n Improving the quality of the surgical field and providing a bloodless FESS in children is attainable with TIVA. TIVA using a combination of remifentanil and propofol is superior to BA, even with the use of additional potent hypotensive agents such as esmolol. Both techniques are safe and effective in inducing controlled hypotension in children at a target mean arterial blood pressure of 50 mm Hg.", "The purpose of this study was to examine the comparative effects of propofol and fentanyl on cerebral oxygenation during normothermic cardiopulmonary bypass and postoperative cognitive dysfunction.\n One hundred eighty patients scheduled for elective coronary artery bypass grafting were randomly divided into two groups: propofol group (n = 90) and fentanyl group (n = 90). After induction of anesthesia, a fiberoptic oximetry oxygen saturation catheter was inserted into the right jugular bulb to monitor jugular venous oxygen hemoglobin saturation continuously. Hemodynamic measurements and arterial and jugular venous blood gases were measured at seven time points. All patients underwent a battery of neurologic and neuropsychological tests on the day before the operation and at 6 months after the operation.\n Cerebral desaturation (defined as a jugular venous oxygen hemoglobin saturation value less than 50%) during cardiopulmonary bypass was more frequent in the fentanyl group than in the propofol group. Cerebral desaturation time (duration when jugular venous oxygen hemoglobin saturation was less than 50%) and the ratio of cerebral desaturation time to total cardiopulmonary bypass time in the fentanyl group differed significantly from those in the propofol group (fentanyl group: 27 +/- 14 minutes, 20% +/- 9%; propofol group: 18 +/- 11 minutes, 14% +/- 7%, respectively, p < 0.05). There was no significant difference in postoperative cognitive dysfunction at 6 months after operation between the two groups (propofol group: 5 of 77, 6%; fentanyl group: 5 of 75, 7%).\n Propofol preserved cerebral oxygenation state estimated by jugular venous oxygenation during cardiopulmonary bypass compared with the fentanyl group. However, propofol did not affect postoperative cognitive dysfunction.", "To assess the effect of monitoring the encephalogram bispectral index (BIS) during outpatient surgery. Outcome measures were amount of propofol administered, awakening and discharge.\n Forty consecutive outpatient surgery patients were studied. The patients gave informed consent and received general intravenous anesthesia with propofol administered through a laryngeal mask using a computerized system (Diprifusor(R)). Two groups were formed: in group A, BIS was monitored, although the information was hidden from the anesthesiologists, who used the usual signs (loss of blinking reflex, pupil size and hemodynamic response) to guide anesthesia; in group B the anesthesiologists used BIS monitoring to guide propofol administration. Measurements were blood pressure, heart rate and BIS at six times during the procedure (T1-T6). Other data recorded were age, weight, height, propofol consumption in relation to weight and duration of procedure, consumption of rocuronium and alfentanil, duration of propofol infusion, time from withdrawal of propofol until eye opening, duration of stay in the post-anesthesia intensive care unit and time until total recovery. A questionnaire assessed the presence of intraoperative awareness and degree of satisfaction. The data were analyzed by Student's t and a chi square tests, with statistical significance at p < 0.05.\n Demographic variables (age, weight and height) were similar, as were duration of propofol infusion, total dose of alfentanil and rocuronium, evolution of blood pressure and heart rate. Statistically significant differences in BIS were observed at two times, T4 and T5; total propofol administered was 32.6% lower in group B; and time until eye opening was significantly shorter in group B. No significant differences were observed for time until full recovery. No instances of intraoperative awareness were reported and satisfaction was high in both groups.\n BIS monitoring allows for propofol titration that leads to a mean reduction of 32.6% in consumption, shortening the time until eye opening without causing intraoperative awareness or reducing patient satisfaction.", "Few studies have compared the clinical profile of target-controlled infusions of propofol with that of manually-controlled infusions. Fifty-four ASA physical status I or II patients scheduled for an elective otorhinolaryngology endoscopy performed under general anesthesia with spontaneous ventilation were enrolled in this prospective randomized study to compare the clinical outcome of such administrations. Before induction, all patients received a single alfentanil bolus dose (10 microg/kg). Propofol administration was adapted to maintain absence of movement, hemodynamic stability, and efficient spontaneous ventilation. When compared with the Manually-Controlled Infusion group, in the Target-Controlled Infusion group there were fewer movements at insertion of the laryngoscope (14.8% vs. 44.4%), improved hemodynamic stability (largest variations of mean arterial blood pressure <10% of control values, versus 20%), fewer episodes of apnea, and less respiratory acidosis after endoscopy (pH = 7.37 +/- 0.05 and PaCO(2) = 50 +/- 7 mm Hg versus pH = 7.28 +/- 0.06 and PaCO(2) = 58 +/- 9 mm Hg); the recovery was also shorter (time to opening eyes or verbal response, 4.6 +/- 2.0 min and 6.8 +/- 2.5 min versus 10.8 +/- 7.3 min and 15.7 +/- 7.1 min). Propofol consumption was comparable in the two groups. Targeting the effect-site concentration improved the time course of the propofol drug effect during direct laryngoscopy performed during spontaneous ventilation when compared with manual infusion.\n This study compares the clinical profile of propofol anesthesia for direct laryngoscopy with spontaneous ventilation when the drug is administered either as a manually controlled infusion or by targeting the effect-site concentration through a target-controlled infusion (TCI) device. TCI improves the time course of propofol effects." ]	Using propofol to achieve deliberate hypotension may improve the surgical field, but the effect is small. Deliberate hypotension with propofol did not decrease TBL and operation time. RCTs with good quality methodology and large sample size are required to investigate the effectiveness of deliberate hypotension with propofol for FESS.
CD000400	[ "2904006", "2522062", "2972171", "2646087", "2972167", "12338165", "16038370", "2974428", "12586320", "20159179", "8328732", "6133791", "1872778" ]	[ "Prevention of NSAID-induced gastric ulcer with misoprostol: multicentre, double-blind, placebo-controlled trial.", "A randomized, prospective comparison of endocrine changes induced with intranasal leuprolide or danazol for treatment of endometriosis.", "Placebo-controlled comparison of danazol and high-dose medroxyprogesterone acetate in the treatment of endometriosis after conservative surgery.", "Effect of ranitidine on gastroduodenal mucosal damage induced by nonsteroidal antiinflammatory drugs.", "Placebo-controlled comparison of danazol and high-dose medroxyprogesterone acetate in the treatment of endometriosis.", "Control of IUD-induced bleeding by three non-steroidal anti-inflammatory drugs.", "A randomized, parallel, comparative study of the efficacy and safety of nafarelin versus danazol in the treatment of endometriosis in Taiwan.", "Danazol and medroxyprogesterone acetate inefficacious in the treatment of infertility in endometriosis.", "A study of co-treatment of nonsteroidal anti-inflammatory drugs (NSAIDs) with misoprostol for cervical priming before suction termination of first trimester pregnancy.", "A randomized prospective trial comparing the levonorgestrel-releasing intrauterine system with thermal balloon ablation for the treatment of heavy menstrual bleeding.", "Duodenal and gastric ulcer prevention with misoprostol in arthritis patients taking NSAIDs. Misoprostol Study Group.", "Dysmenorrhea in women with intrauterine contraceptive device. Treatment with a prostaglandin synthetase inhibitor, naproxen.", "Randomized trial of 2 hormonal and 2 prostaglandin-inhibiting agents in women with a complaint of menorrhagia." ]	[ "A double-blind, placebo-controlled study was carried out to see whether the synthetic E prostaglandin, misoprostol, would prevent gastric ulcer induced by non-steroidal anti-inflammatory drugs (NSAIDs). 420 patients with osteoarthritis and NSAID-associated abdominal pain were studied; they were receiving ibuprofen, piroxicam, or naproxen. Endoscopy was done at entry and after 1, 2, and 3 months of continuous treatment with 100 micrograms or 200 micrograms misoprostol or placebo, given four times daily with meals and at bedtime, concurrently with the NSAID. Abdominal pain was rated independently by patients and physicians. A treatment failure was defined as development of a gastric ulcer. Gastric ulcers (0.3 cm in diameter or greater) occurred less frequently (p less than 0.001) in both misoprostol treatment groups (5.6% 100 micrograms and 1.4% 200 micrograms) than in the placebo group (21.7%). The significant difference in ulcer formation between the placebo and the misoprostol treatment groups remained when comparisons were restricted to ulcers greater than 0.5 cm in diameter (12.3% placebo, 4.2% 100 micrograms misoprostol, and 0.7% 200 micrograms misoprostol). Mild to moderate, self-limiting diarrhoea was the most frequently reported adverse effect attributed to misoprostol. These results provide the first clear indication that NSAID-induced ulcers are preventable.", "A prospective, randomized trial compared hormonal changes induced with intranasal leuprolide 1.6 mg/day to danazol 800 mg/day for treatment of endometriosis. Both regimens induced anovulation and ovarian suppression in all subjects. Mean estradiol (E2) and progesterone (P) levels were suppressed with both regimens, but were lower with leuprolide. There was no difference in cumulative follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, although at times during treatment mean levels of these hormones were lower with leuprolide. Higher P levels in the danazol group, most likely of adrenal origin, indicated a suppressive effect on adrenal steroidogenesis. Symptomatic improvement was significant in both groups. Laparoscopy after treatment also demonstrated a decrease in endometriosis scores in both groups. At 12 months after treatment, cumulative pregnancy and live birth rates were similar in both groups. Leuprolide offers an attractive alternative to danazol for the medical treatment of endometriosis.", "To evaluate the clinical value of postoperative hormone therapy in endometriosis, 60 patients with advanced disease were randomized to receive in a double-blind study danazol (200 mg, 3 times daily), medroxyprogesterone acetate (MPA) (100 mg daily) or placebo post-operatively for 6 months. Treatment efficacy was evaluated clinically and at laparoscopy 6 months after medication. In relation to placebo, danazol and high-dose MPA treatments, which did not differ from each other in efficacy, significantly alleviated pelvic pain. In addition, the peritoneal endometriosis lesions found at 6-months laparoscopy were significantly smaller in the MPA and danazol groups than in the placebo group. Breakthrough bleeding, weight gain and acne complicated danazol treatment but only breakthrough bleeding complicated MPA treatment. These data suggest that postoperative treatment of advanced endometriosis with high-dose MPA or danazol is clinically beneficial.", "The effect of ranitidine in preventing mucosal damage caused by nonsteroidal antiinflammatory drugs (NSAIDs) was evaluated for eight weeks in a prospective study of 144 patients requiring NSAIDs. Patients with normal endoscopic findings were randomly assigned to receive either ranitidine 150 mg twice daily or placebo for eight weeks, along with either ibuprofen, indomethacin, naproxen, sulindac, or piroxicam. Duodenal damage was significantly less in the ranitidine group compared with the placebo group by weeks 4 and 8 (P less than or equal to 0.01). Duodenal ulcers did not develop in any patients on ranitidine (0/57) compared with 4/49 patients (8%) on placebo (P = 0.02). No significant difference was found between treatment groups with respect to gastric damage; 6/60 (10%) in the ranitidine group compared with 6/50 (12%) in the placebo group developed gastric ulcers. These findings suggest that acid suppression is of greater importance for mucosal protection in the duodenum than in the stomach, where other defense mechanisms may be operative. While ranitidine is an effective prophylaxis for NSAID-induced damage in the duodenum, further studies are needed to define specific risk groups and to assess the potential usefulness of more complete acid suppression in preventing gastric mucosal damage.", "A prospective, double-blind, placebo-controlled study was designed to evaluate the clinical efficacy and tolerance of danazol and high-dose medroxyprogesterone acetate (MPA) in the treatment of mild-moderate endometriosis. After laparoscopical confirmation of endometriosis, 59 patients were randomized to receive danazol (200 mg 3 times daily), MPA (100 mg daily) or placebo for 6 months. Clinical examinations were done before and 1, 3, 6 and 12 months after the beginning of the study, and a 2nd laparoscopy 6 months after termination of the medication. Eighteen patients in the danazol group, 16 in the MPA group and 17 in the placebo group completed the trial. Total or partial resolution of peritoneal implants was observed in 60% of the patients receiving danazol and in 63% of the patients receiving MPA. In the placebo group, resolution was observed in 18%, while the size of the implants was estimated to be increased in 23% of the patients. In relation to placebo, danazol and MPA significantly alleviated endometriosis-associated pelvic pain, lower back pain and defecation pain, but they did not differ from each other in these actions. The appearance of acne, muscle cramps, edema, weight gain and spotting bleeding complicated MPA treatment. The present results indicate that because of good efficacy and tolerance, high-dose MPA is a useful alternative in the hormonal treatment of endometriosis.", "Administration of nonsteroidal anti-inflammatory drugs (NSAIDs) reduced excessive IUD-induced bleeding. The effect of 3 different oral NSAIDs, namely indomethacin, Alclofenac, and flufenamic acid, on menstrual blood loss (MBL) and pain among women fitted with copper IUDs was studied and compared with a placebo on a randomized single blind basis. Each drug was given to 6 subjects (18 cases) over 2 consescutive cycles and was either preceded or followed by placebo for 2 more cycles. 1/2 of the cases on each drug started placebo medication in the 1st 2 months while the other 1/2 started by the drug. The oral treatment was begun on the 1st day of menstrual bleeding or spotting. Estimation of the daily MBL was done by the alkaline hematin method with mechanical extraction of sanitary pads. The 3 drugs tested in this study induced a significant reduction in MBL: maximum reduction by flufenamic acid medication, less with Alclofenac, and least with indomethacin medication. However, these reductions were not statistically different, and marked improvement in IUD-induced pain was observed under the effect of the 3 drugs.", "The purpose of this study was to evaluate the efficacy and safety of nafarelin, a gonadotropin-releasing hormone (GnRH) analogue, versus danazol in the treatment of women with endometriosis in Taiwan.\n Fifty-nine women with laparoscopically and pathologically confirmed endometriosis were randomized to receive nafarelin or danazol for 180 days. Efficacy was assessed from mean changes in laparoscopy score (LS) and total symptom severity score (TSSS). Adverse events (AEs) and laboratory parameters, including hematology, hepatic function, blood pressure, and lipid levels, were monitored for safety evaluations.\n All demographic and baseline factors, except body weight, were comparable between the 2 treatment groups. Both nafarelin and danazol satisfactorily resolved pelvic tenderness, induration, pelvic pain, dysmenorrhea and dyspareunia. No significant differences were noted in efficacy endpoints between nafarelin and danazol regarding LS and TSSS at 90 and 180 days of treatment. No significant difference was observed between the 2 groups regarding the overall incidence of AEs, except for laboratory-related AEs. However, nafarelin tended to have less impact than danazol on aspartate transaminase and alanine transaminase, and nafarelin was better tolerated than danazol regarding changes in lipid profiles. Both treatments had little or no effect on hematologic parameters.\n Nafarelin and danazol demonstrated similar clinical efficacy, but nafarelin was associated with fewer laboratory changes and a stable lipid profile, relative to danazol. Moreover, intranasally administered nafarelin is noninvasive, and may be a more comfortable and safer alternative to slow-release injectable GnRH agonists. Based on this study, we suggest that nafarelin, like other GnRH analogues, may be a treatment of choice for Taiwanese women with endometriosis. However, direct comparative studies of nafarelin with slow-release injectable GnRH agonists are now required.", "Danazol (200 mg three times a day) and medroxyprogesterone acetate (MPA, 100 mg a day) were compared with placebo in the treatment of infertility of patients with endometriosis. Twenty-seven patients had medical therapy alone for 6 months, and 22 patients received it after conservative surgery. The clinical characteristics of the patients in the danazol group (n = 18), the MPA group (n = 17), and the placebo group (n = 14) were comparable to each other. The follow-up time was 30 months. The cumulative pregnancy rates, 33% in the danazol group (n = 6), 42% in the MPA group (n = 7), and 46% in the placebo group (n = 6), did not differ significantly from each other. The time to pregnancy after the start of therapy was 17.7 +/- 8.4 (standard deviation [SD]) months in the danazol group, 18.0 +/- 9.0 months in the MPA group and 10.0 +/- 5.8 months in the placebo group with no significant difference between the groups. The abortion rate was 26%, and there was no significant difference among the groups. Cox multivariant analysis did reveal ovarian endometriosis a prognostically significant negative indicator as regards fecundation in endometriosis (P less than 0.05). In summary, correction of infertility alone does not appear to be an indication for the use of danazol or MPA in the treatment of endometriosis, and ovarian endometriotic lesions but not peritoneal ones do make a worse prognosis as regards fecundation in endometriosis.", "This double-blind randomized control study was conducted to evaluate whether a nonsteroidal anti-inflammatory drug (NSAID) could act as an effective pain control method during first trimester suction abortion, and whether co-treatment of NSAID with misoprostol will decrease the efficacy of the cervical ripening effect of misoprostol. Subjects were randomized to receive misoprostol alone or misoprostol together with diclofenac sodium. Both groups of subjects suffered from similar incidence of preoperative side effects. Co-treatment of NSAID with misoprostol did not attenuate the cervical ripening efficacy of misoprostol. There was no significant pain reduction in the group treated with NSAID, except that a marginal benefit was found in the subgroup of multiparous women. About two thirds of the subjects in both treatment groups found that this was a satisfactory pain relief method during the procedure.", "Use of the levonorgestrel-releasing intrauterine system (LNG-IUS) was compared with thermal balloon ablation (TBA) for the treatment of heavy menstrual bleeding (HMB).\n A prospective randomized trial comparing the LNG-IUS (n=30 women) and TBA (n=28 women).\n Hemoglobin levels increased (p<.001) and blood loss was reduced (p<.001) in both groups after 1 year of treatment. Menstrual bleeding was less in the LNG-IUS group compared to the TBA group at 6 and 12 months of treatment (p=.035 and p=.048, respectively). Intermenstrual bleeding was significantly less in the TBA group at 6 months compared to the LNG-IUS group (p=.044); however, there was no significant difference at 12 months (p=.129). No difference was found in psychological aspects between pre- and posttreatment variables in either of the groups (p=.537).\n Both the LNG-IUS and TBA appear to be effective in controlling HMB; however, posttreatment uterine bleeding patterns are different.\n Copyright (c) 2010 Elsevier Inc. All rights reserved.", "To determine the efficacy of misoprostol for the prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced duodenal and gastric ulcers in arthritis patients receiving NSAID therapy.\n A randomized, double-blind, multicenter, placebo-controlled trial.\n Six hundred thirty-eight private, Veterans Affairs, health maintenance, and academic practices.\n Six hundred thirty-eight patients with chronic inflammatory or noninflammatory arthritis who were taking an NSAID but who did not have a gastric or duodenal ulcer on screening endoscopy received treatment with ibuprofen, piroxicam, naproxen, sulindac, tolmetin, indomethacin, or diclofenac daily for 3 months. Four hundred fifty-five (71%) patients completed the trial.\n Patients meeting the entry criteria were randomized to receive either misoprostol, 200 micrograms, or placebo, four times a day for 12 weeks.\n The endoscopy was repeated at 4, 8, and 12 weeks. The development of a duodenal or gastric ulcer (defined as a circumscribed mucosal defect > or = 0.5 cm in diameter and with perceptible depth) was regarded as prophylactic failure.\n By 12 weeks, a duodenal ulcer developed in 2 of 320 (0.6%; 95% CI, 0.2% to 3.9%) patients randomized to receive misoprostol, compared with 15 of 323 (4.6%; CI, 2.8% to 8%) patients receiving placebo (P = 0.002). A gastric ulcer developed in 6 of 320 (1.9%; (CI, 0.8% to 4.4%) patients, compared with in 25 of 323 (7.7%; CI, 5.1% to 11.4%), respectively.\n Misoprostol significantly lowers the frequency of both duodenal and gastric ulcer development in patients who require long-term therapy with NSAIDS.", "Twenty-one women with intrauterine contraceptive devices (IUCD) and severe dysmenorrhea were studied. All the women who participated in the study had primary dysmenorrhea of varying intensities. The insertion of IUCD increased the intensity of dysmenorrheic pain. The effect of naproxen (Naprosyn) on pain alleviation was studied in a double-blind cross-over trial using naproxen and placebo. The effect of naproxen was significantly better than that of placebo (P less than 0.01). No severe side effects occurred during the treatment. There was no difference in the duration and amount of the menstrual blood flow during naproxen treatment compared to placebo according to the women's own judgement.", "A series of 45 ovulatory women with a complaint of menorrhagia were randomized into 3 treatment groups, before receiving therapy with mefenamic acid in 2 cycles and 1 of 3 other agents in 2 cycles: naproxen (group 1; n = 14), a low dose monophasic combined oral contraceptive (group 2; n = 12) or low dose danazol (group 3; n = 12). Menstrual blood loss was measured in 2-4 control cycles and during therapy. Mefenamic acid reduced measured blood loss by 20%; 38%; and 39% in groups 1-3 respectively. Naproxen reduced blood loss by 12%; the oral contraceptive by 43%; and danazol by 49%. There was no statistically significant difference in blood loss reduction (mean of 2 cycles) between any of the treatments, although women on danazol experienced a dramatic and highly significant further reduction in blood loss after the first treatment cycle (p less than 0.003). These were all effective therapies in a majority of women, but some 'non-responders' were seen in each group. The 'non-responders' had a significantly lower pretreatment blood loss than responders. Several women in group 1 showed anomalous responses to prostaglandin inhibitors with consistent and substantial exacerbation of menorrhagia during therapy. A number of reasonable therapies exist for the medical treatment of menorrhagia, but because none is suitable for everyone management needs to be individualized for each patient." ]	NSAIDs reduce HMB when compared with placebo but are less effective than tranexamic acid, danazol or LNG IUS. However, adverse events are more severe with danazol therapy. In the limited number of small studies suitable for evaluation, no significant difference in efficacy was demonstrated between NSAIDs and other medical treatments such as oral luteal progestogen, ethamsylate, OCC or another type of intrauterine system, Progestasert.
CD000004	[ "4586680", "3102211" ]	[ "A randomised double blind clinical trial of abdominal decompression for the prevention of pre-eclampsia.", "Randomized controlled trial of very early continuous distending pressure in the management of preterm infants." ]	[ "nan", "Application of continuous distending pressure at birth (very early CDP) should stabilize the immature airways and reduce the severity of respiratory distress syndrome (RDS) in preterm infants. Eighty-two preterm infants of less than 32 weeks gestation were randomly assigned at birth to early treatment group (TG), in which CDP of 6 cm water pressure was applied at birth by the nasopharyngeal route (NP-CDP), or to control group (CG), in which CDP was applied when indicated for established criteria (pO2 less than 50 mmHg in FiO2 greater than 0.5). Characteristics of the infants in the two groups were comparable. No statistically significant difference between the two groups was found in the incidence of RDS. The course of RDS, and oxygen and ventilatory requirements also did not appear to be changed. In blood gas parameters of most of the time frames, no significant difference was found between the two groups when the results were analyzed according to the assigned group. When the results were analyzed separately for the infants who developed RDS, infants in TG appear to have fared worse from the therapy in terms of oxygenation, as indicated by significantly higher FiO2 (P less than 0.01) and lower a/A (P less than 0.01) values on the third day of the course of RDS, as compared to infants in CG. The incidence of complications was comparable in the two groups. Four infants from TG (9.3%) and one from CG (2.6%) died (P = NS). We conclude that VECDP by nasopharyngeal route does not reduce the incidence of RDS and does not appear to improve the outcome and may worsen the severity of RDS when compared to application of CDP for established criteria." ]	Due to the methodological limitations of the studies, the effects of therapeutic abdominal decompression are not clear. The apparent improvements in birthweight and perinatal mortality warrant further evaluation of abdominal decompression where there is impaired fetal growth and possibly for women with pre-eclampsia.
CD000247	[ "18209140", "15689289", "11340701", "11978254", "9463979", "380773" ]	[ "Efficacy of isotonic nasal wash (seawater) in the treatment and prevention of rhinitis in children.", "Are antibiotics beneficial for patients with sinusitis complaints? A randomized double-blind clinical trial.", "Intranasal beclomethasone dipropionate in the treatment of common cold.", "Do delayed prescriptions reduce the use of antibiotics for the common cold? A single-blind controlled trial.", "The end of antibiotic treatment in adults with acute sinusitis-like complaints in general practice? A placebo-controlled double-blind randomized doxycycline trial.", "Flunisolide nasal spray for perennial rhinitis in children." ]	[ "To evaluate the potential of nasal isotonic saline application to prevent reappearance of cold and flu in children during the winter.\n Prospective, multicenter, parallel-group, open, and randomized comparison.\n Eight pediatric outpatient clinics.\n A total of 401 children (aged 6-10 years) with uncomplicated cold or flu.\n We randomly assigned patients to 2 treatment groups, one with just standard medication, the other with nasal wash with a modified seawater solution (Physiomer) plus standard medication, and observed them for 12 weeks.\n The primary efficacy end points were nasal symptoms resolution during acute illness (visits 1 and 2). We also looked for reappearance of cold or flu, consumption of medication, complications, days off school, and reported days of illness during the following weeks when preventive potential was evaluated (visits 3 and 4).\n At visit 2, patients in the saline group achieved primary end points (measured on a 4-point numeric scale on which 1 indicated no symptoms and 4, severe symptoms) in the parameters nasal secretion and obstruction (mean scores vs nonsaline group, 1.79 vs 2.10 and 1.25 vs 1.58, respectively) (P < .05 for both). During the prevention phase (at visit 3, 8 weeks after study entry) patients in the saline group showed significantly lower scores in sore throat, cough, nasal obstruction, and secretion (P < .05 for all). By visit 3, significantly fewer children in the saline group were using antipyretics (9% vs 33%), nasal decongestants (5% vs 47%), mucolytics (10% vs 37%), and systemic antiinfectives (6% vs 21%) (P < .05 for all). During the same period children in the saline group also reported significantly fewer illness days (31% vs 75%), school absences (17% vs 35%), and complications (8% vs 32%) (P < .05 for all). Similar results were found at the final visit.\n Children in the saline group showed faster resolution of some nasal symptoms during acute illness and less frequent reappearance of rhinitis subsequently.", "Sinusitis is the fifth most common reason for patients to visit primary care physicians, yet clinical outcomes relevant to patients are seldom studied.\n To determine whether patients with purulent rhinitis, \"sinusitis-type symptoms,\" improved with antibiotics. Second, to examine a clinical prediction rule to provide preliminary validation data.\n Prospective clinical trial, with double-blinded placebo controlled randomization. The setting was a suburb of Washington, DC, from Oct 1, 2001, to March 31, 2003. All participants were 18 years or older, presenting to a family practice clinic with a complaint of sinusitis and with pus in the nasal cavity, facial pressure, or nasal discharge lasting longer than 7 days. The main outcome measures were resolution of symptoms within a 14-day follow-up period and the time to improvement (days).\n After exclusion criteria, 135 patients were randomized to either placebo (n=68) or amoxicillin (n=67) for 10 days. Intention-to-treat analyses showed that 32 (48%) of the amoxicillin group vs 25 (37%) of the placebo group (P=.26) showed complete improvement by the end of the 2-week follow-up period (relative risk=1.3; 95% confidence interval [CI], 0.87-1.94]). Although the rates of improvement were not statistically significantly different at the end of 2 weeks, the amoxicillin group improved significantly earlier, in the course of treatment, a median of 8 vs 12 days, than did the placebo group (P=.039).\n For most patients with sinusitis-type complaints, no improvement was seen with anti-biotics over placebo. For those who did improve, data suggested there is a subgroup of patients who may benefit from antibiotics.", "Sinusitis is usually considered a complication of viral rhinitis. Virus infections in the upper respiratory tract lead to mucosal swelling, which may obstruct paranasal sinus outflow, resulting in infection in the paranasal sinuses. Topical nasal steroids have been found beneficial in a variety of acute and chronic nasal conditions including allergic and nonallergic rhinitis and chronic rhinosinusitis. The purpose of this study was to examine whether the intranasal inhalation powder beclomethasone dipropionate (BDP) 400 micrograms/day treatment has a beneficial or harmful effect on symptoms and signs of common cold, and whether or not it can prevent common cold complications. A total of 54 patients were randomized, 26 into the placebo-group and 28 into the BDP group. During the 14-day follow-up, there were on an average 10.3 symptomatic days in the placebo group and 10.7 days in the BDP group (p = 0.72). The use of intranasal BDP in the treatment of common cold neither reduced symptoms caused by inflammation nor did it shorten the recovery time. On the other hand, because BDP does not increase the risk of complications or significantly prolong the recovery during the common cold, there is no need to discontinue its use in the patients with allergic rhinitis or nasal polyposis.", "To test the use of a delayed prescription compared with instructions to take antibiotics immediately in patients presenting to family physicians with upper respiratory tract infections (common colds).\n Randomized controlled single-blind study.\n Subjects were 129 patients presenting with the common cold who requested antibiotics or whose physicians thought they wanted them. All patients were in a family practice in Auckland, New Zealand, consisting of 15 physicians (9 male, 6 female) who had completed medical school between 1973 and 1992.\n Outcomes were antibiotic use (taking at least 1 dose of the antibiotic), symptom scores, and responses to the satisfaction questions asked at the end of the study.\n Patients in the delayed-prescription group were less likely to use antibiotics (48%, 95% CI, 35%-60%) than were those instructed to take antibiotics immediately (89%, 95% CI, 76%-94%). Daily body temperature was higher in the immediate-prescription group. The lack of difference in the symptom score between the 2 groups suggests that there is no danger in delaying antibiotic prescriptions for the common cold.\n Delayed prescriptions are a safe and effective means of reducing antibiotic consumption in patients with the common cold. Clarification of patient expectations for antibiotics may result in a lower prescription rate. When the patient demands a prescription, delaying its delivery has the potential to provide gentle education.", "Acute sinusitis-like complaints are very common and are usually treated with antibiotics in spite of the lack of evidence for the effectiveness of antibiotic therapy and the increasing number of resistant strains.\n To assess the effectiveness of doxycycline in adults with acute sinusitis-like complaints in general practice.\n The effects of doxycycline in a placebo-controlled, double-blind, randomized trial were assessed in adults consulting their general practitioner (GP) with complaints after a common cold or influenza, pain in the head when bending forward, purulent nasal discharge, predominantly unilateral maxillary pain, toothache, or pain when chewing. Primary outcome events were the resolution of facial pain and the resumption of daily activities. Treatment differences were assessed by means of Kaplan-Meier curves and hazard ratios. The follow-up period was 42 days.\n No significant difference was found in time to recover between the doxycycline-treated group and the placebo-treated group. However, the adjusted hazard ratio for the group receiving doxycycline was 1.17 (95% CI = 0.87-1.57) for the resolution of pain and 1.31 (95% CI = 0.96-1.78) for the resumption of daily activities. After 10 days, 85% of all patients reported improvement and 60% were completely cured. Side effects were reported by 17% of the doxycycline-treated group, with two patients withdrawing because of side effects.\n Data from this study indicate that doxycycline does not add to the effectiveness of decongestive nose drops and steam inhalation in treating acute sinusitis-like complaints in general practice adults.", "Twenty-seven children with perennial rhinitis entered a double-blind cross-over study comparing nasal sprays of flunisolide---a new topical corticosteroid---and placebo. Symptoms were assessed over two consecutive monthly periods with each treatment. Weekly diary cards, monthly clinical assessments, and end-of-trial preferences all favoured the active drug. At the end of the trial 20 patients preferred the treatment month with flunisolide, four preferred the placebo month, and two rated the periods equally. Side effects were mild, the commonest being transient nasal stinging. Seventeen children who derived benefit from flunisolide continued with the treatment for a six-month open-study period. Many reduced the dosage from three times to twice or once daily without losing benefit. The effect of flunisolide on the pituitary-adrenal axis was assessed in seven children by measuring the 0900 blood cortisol concentrations at two-month intervals over the six months. No effect was observed. The results show that flunisolide is effective and safe for the treatment and prophylaxis of perennial rhinitis in children." ]	There is no evidence of benefit from antibiotics for the common cold or for persisting acute purulent rhinitis in children or adults. There is evidence that antibiotics cause significant adverse effects in adults when given for the common cold and in all ages when given for acute purulent rhinitis. Routine use of antibiotics for these conditions is not recommended.
CD007020	[ "12499335", "15693087", "19960200", "20639712" ]	[ "Improved antioxidant and fatty acid status of patients with cystic fibrosis after antioxidant supplementation is linked to improved lung function.", "Effects of vitamins C and E on oxidative stress markers and endothelial function in patients with systemic lupus erythematosus: a double blind, placebo controlled pilot study.", "Oxidative stress biomarkers in mitochondrial myopathies, basally and after cysteine donor supplementation.", "Supplementation with fatty acids influences the airway nitric oxide and inflammatory markers in patients with cystic fibrosis." ]	[ "Oxidative stress, as measured by 8-iso-prostaglandin F(2)(alpha) (8-iso-PGF(2)(alpha)), and depleted antioxidant defenses were shown in stable cystic fibrosis (CF) patients. The plasma fatty acid status of CF patients was linked to oxidative stress after respiratory exacerbations.\n We examined changes in plasma 8-iso-PGF(2)(alpha), antioxidant defenses, plasma fatty acid status, and clinical markers resulting from short-term antioxidant supplementation.\n Forty-six CF patients were randomly assigned to either group A [low dose of supplement (10 mg vitamin E and 500 micro g vitamin A)] or group B [high dose of supplement (200 mg vitamin E, 300 mg vitamin C, 25 mg beta-carotene, 90 micro g Se, and 500 micro g vitamin A)]. Plasma concentrations of 8-iso-PGF(2)(alpha), vitamins E and C, beta-carotene, zinc, selenium, and copper; plasma fatty acid composition; erythrocyte glutathione peroxidase (EC 1.11.1.9) and superoxide dismutase (EC 1.15.1.1) activities; lung function; and dietary intake were measured before and after 8 wk of supplementation.\n Antioxidant defenses in group B improved, whereas those in group A did not: in groups B and A, the mean (+/- SEM) changes (Delta) in vitamin E were 10.6 +/- 1.5 and -1.9 +/- 0.9 micro mol/L, respectively (P < 0.001), (Delta)beta-carotene were 0.1 +/- 0.04 and -0.01 +/- 0.02 micro mol/L, respectively (P = 0.007), (Delta)selenium were 0.51 +/- 0.10 and -0.09 +/- 0.04 micro mol/L, respectively (P < 0.001), and (Delta)glutathione peroxidase activity were 1.3 +/- 0.3 and -0.3 +/- 0.6 U/g hemoglobin, respectively (P = 0.016). There were no significant differences between the groups in Delta8-iso-PGF(2)(alpha), (Delta)vitamin C, (Delta)fatty acid composition, (Delta)superoxide dismutase activity, (Delta)lung function, or (Delta)white cell count. Within group B, (Delta)beta-carotene correlated with (Delta)percentage of forced vital capacity (r = 0.586, P = 0.005), (Delta)selenium correlated with (Delta)percentage of forced expiratory volume in 1 s (r = 0.440, P = 0.046), and (Delta)plasma fatty acid concentrations correlated with (Delta)percentage of forced expiratory volume in 1 s (r = 0.583, P = 0.006) and Delta8-iso-PGF(2)(alpha) (r = 0.538, P = 0.010).\n Whereas increased beta-carotene, selenium, and fatty acid concentrations are linked to improved lung function, increased plasma fatty acid concentrations are linked to oxidative stress. If oxidative stress is deemed to be important to the clinical outcome of CF patients, means of reducing oxidative stress while maintaining a high-fat, high-energy diet must be investigated.", "Patients with systemic lupus erythematosus (SLE) experience excess morbidity and mortality due to coronary artery disease (CAD) that cannot be fully explained by the classical CAD risk factors. Among emerging CAD risk factors, oxidative stress is currently being emphasized. We evaluated the effects of longterm antioxidant vitamins on markers of oxidative stress and antioxidant defense and endothelial function in 39 patients with SLE.\n Patients were randomized to receive either placebo or vitamins (500 mg vitamin C and 800 IU vitamin E daily) for 12 weeks. Markers of oxidative stress included malondialdehyde (MDA) and allantoin. Antioxidants measured included erythrocyte superoxide dismutase and glutathione peroxidase, plasma total antioxidant power (as FRAP value), and ascorbic acid and vitamin E concentrations. Endothelial function was assessed by flow-mediated dilatation (FMD) of the brachial artery and plasma concentration of von Willebrand factor (vWF) and plasminogen activator inhibitor type 1 (PAI-1). Primary outcome of the study included the change in lipid peroxidation as revealed by MDA levels. Secondary outcomes included changes in allantoin and antioxidant levels and change in endothelial function.\n After treatment, plasma ascorbic acid and alpha-tocopherol concentrations were significantly (p < 0.05) increased only in the vitamin-treated group, associated with a significant decrease (p < 0.05) in plasma MDA. Other oxidative stress markers and antioxidant levels remained unchanged in both groups. FMD and vWF and PAI-1 levels remained unchanged in both groups.\n Combined administration of vitamins C and E was associated with decreased lipid peroxidation, but did not affect endothelial function in patients with SLE after 3 months of therapy.", "Mitochondrial diseases are due to impairment of the mitochondrial respiratory chain. A plausible pathogenic mechanism leading to cellular dysfunction and phenotypic expression is oxidative stress, but there are surprisingly few clinical studies on this subject. Glutathione (GSH) deficiency has been reported in mitochondrial diseases, and the biosynthesis of glutathione depends on cysteine availability. We have examined oxidative stress biomarkers [advanced oxidation protein products (AOPP) and ferric reducing antioxidant power (FRAP)] in blood samples from 27 patients and 42 controls. AOPP levels were greater in patients than in controls (P value <0.00001). Therefore, we performed a double-blind cross-over study to evaluate if 30-day supplementation with a whey-based cysteine donor could modify these markers, reduce lactate concentration during aerobic exercise, or enhance muscular strength and quality of life. Treatment did not modify lactate concentration, clinical scale (MRC) or quality of life (SF-36), but significantly reduced oxidative stress levels. Our findings reinforce the notions that in mitochondrial diseases oxidative stress is important and can be reduced by administration of a cysteine donor. Oxidative stress biomarkers may be useful to detect redox imbalance in mitochondrial diseases and to provide non-invasive tools to monitor disease status.", "To obtain a balance in the fatty acid (FA) metabolism is important for the inflammatory response and of special importance in cystic fibrosis (CF), which is characterized by impaired FA metabolism, chronic inflammation, and infection in the airways. Nitric oxide (NO) has antimicrobial properties and low nasal (nNO) and exhaled NO (FENO), commonly reported in CF that may affect bacterial status. The present study investigates the effect of different FA blends on nNO and FENO and immunological markers in patients with CF.\n Forty-three patients with CF and \"severe\" mutations were consecutively enrolled in a randomized double-blind placebo-controlled study with 3 FA blends containing mainly n-3 or n-6 FA or saturated FA acting as placebo. FENO, nNO, serum phospholipid concentrations of FA, and biomarkers of inflammation were measured before and after 3 months of supplementation.\n Thirty-five patients in clinically stable condition completed the study. The serum phospholipid FA pattern changed significantly in all 3 groups. An increase of the n-6 FA, arachidonic acid, was associated with a decrease of FENO and nNO. The inflammatory biomarkers, erythrocyte sedimentation rate, and interleukin-8 decreased after supplementation with n-3 FA and erythrocyte sedimentation rate increased after supplementation with n-6 FA.\n This small pilot study indicated that the composition of dietary n-3 and n-6 FA influenced the inflammatory markers in CF. FENO and nNO were influenced by changes in the arachidonic acid concentration, supporting previous studies suggesting that both the lipid abnormality and the colonization with Pseudomonas influenced NO in the airways." ]	There appears to be conflicting evidence regarding the clinical effectiveness of antioxidant supplementation in CF. Based on the evidence, antioxidants appear to decrease quality of life and oxidative stress; however, few trials contributed data towards analysis. Further trials examining clinically important outcomes and elucidation of a clear biological pathway of oxidative stress in CF are necessary before a firm conclusion regarding effects of antioxidants supplementation can be drawn.
CD004503	[ "8951252", "20947097", "8545223", "9347370" ]	[ "The Provo multicenter early high-frequency oscillatory ventilation trial: improved pulmonary and clinical outcome in respiratory distress syndrome.", "Randomized controlled trial of lung lavage with dilute surfactant for meconium aspiration syndrome.", "Surfactant replacement therapy for meconium aspiration syndrome.", "Patient-initiated, pressure-regulated, volume-controlled ventilation compared with intermittent mandatory ventilation in neonates: a prospective, randomised study." ]	[ "To compare the hospital course and clinical outcome of preterm infants with respiratory distress syndrome treated with surfactant and managed with high-frequency oscillatory ventilation (HFOV) or conventional mechanical ventilation (CV) as their primary mode of ventilator support.\n A prospective randomized clinical trial.\n Three community-based level III neonatal intensive care units.\n A total of 125 neonates who were 35 weeks or less estimated gestation requiring intubation and assisted ventilation for respiratory distress syndrome with arterial to alveolar oxygen ratio less than .50.\n Patients were randomized to continue CV (61 patients) or be changed to HFOV (64 patients) after exogenous surfactant administration (100 mg/kg). HFOV was used in a strategy to promote lung recruitment and maintain lung volume. Protocol respiratory care guidelines were followed; otherwise routine care was provided by each neonatal intensive care unit.\n No differences were noted in demographic features between the two study groups. The study population birth weight was 1.51 +/- .47 kg (mean +/- SD), gestational age was 30.9 +/- 2.5 weeks, and study entry age was 2 to 3 hours. Patients randomized to HFOV demonstrated the following significant findings compared with CV-treated patients: vasopressor support was less intensive; surfactant redosing was not as frequent; oxygenation improved more rapidly and remained higher during the first 7 days; fewer infants required prolonged supplemental oxygen or ventilator support; treatment failure was reduced; more patients survived without chronic lung disease at 30 days; need for continuous supplemental oxygen at discharge was less; frequency of necrotizing enterocolitis illness was lower; there were fewer abnormal hearing tests; and hospital costs were decreased. No differences were seen between the two study groups in the frequency or severity of patent ductus arteriosus, air leak, retinopathy of prematurity, or intraventricular hemorrhage. Length of hospital stay and survival to discharge were similar for HFOV- and CV-treated infants.\n When used early with a lung recruitment strategy, HFOV after surfactant replacement resulted in clinical outcomes consistent with a reduction in both acute and chronic lung injury. Benefit was evident for preterm infants both less than or equal to 1 kg and more than 1 kg. In addition, early HFOV treatment may have had a more global effect on patient health throughout the hospitalization, resulting in reduced morbidity and decreased health care cost.", "To evaluate whether lung lavage with surfactant changes the duration of mechanical respiratory support or other outcomes in meconium aspiration syndrome (MAS).\n We conducted a randomized controlled trial that enrolled ventilated infants with MAS. Infants randomized to lavage received two 15-mL/kg aliquots of dilute bovine surfactant instilled into, and recovered from, the lung. Control subjects received standard care, which in both groups included high frequency ventilation, nitric oxide, and, where available, extracorporeal membrane oxygenation (ECMO).\n Sixty-six infants were randomized, with one ineligible infant excluded from analysis. Median duration of respiratory support was similar in infants who underwent lavage and control subjects (5.5 versus 6.0 days, P = .77). Requirement for high frequency ventilation and nitric oxide did not differ between the groups. Fewer infants who underwent lavage died or required ECMO: 10% (3/30) compared with 31% (11/35) in the control group (odds ratio, 0.24; 95% confidence interval, 0.060-0.97). Lavage transiently reduced oxygen saturation without substantial heart rate or blood pressure alterations. Mean airway pressure was more rapidly weaned in the lavage group after randomization.\n Lung lavage with dilute surfactant does not alter duration of respiratory support, but may reduce mortality, especially in units not offering ECMO.\n Copyright © 2011 Mosby, Inc. All rights reserved.", "The pathophysiology of meconium aspiration syndrome (MAS) is related not only to mechanical obstruction of the airways and chemical injury to the respiratory epithelium but also to surfactant inactivation by meconium. A randomized, controlled study was performed to determine whether high-dose surfactant therapy improves the pulmonary morbidity of term infants ventilated for MAS.\n Forty term infants receiving mechanical ventilation for MAS were enrolled in this trial, in which the infants in the study group (n = 20) received up to four doses of 150 mg (6 mL)/kg beractant (Survanta), instilled every 6 hours by continuous infusion for 20 minutes via a side hole endotracheal tube adapter, and the infants in the control group (n = 20) received 6 mL/kg air placebo.\n Mean arterial-to-alveolar PO2 ratio values increased from 0.09 to 0.11 at 1 and 6 hours with a concomitant slight decrease in oxygenation index values from 23.7 to 19.7 at 1 hour and 20.7 at 6 hours after the first dose of surfactant. Oxygenation improved cumulatively after the second and third dose of surfactant, with mean arterial-to-alveolar PO2 ratios and oxygenation indices of 0.18 and 12.1 at 6 hours after the second dose of surfactant and 0.31 and 5.9 at 6 hours after the third dose of surfactant, eliminating the need for a fourth dose in any infant in the study group. After three doses of surfactant, persistent pulmonary hypertension had resolved in all but one of the infants in the study group versus none of the infants in the control group. No air leaks developed in any of the 20 infants in the study group after surfactant therapy, and only 1 infant required extracorporeal membrane oxygenation. Air leaks developed in 5 of the 20 infants in the control group, and 6 underwent extracorporeal membrane oxygenation. The duration of mechanical ventilation, oxygen therapy, and admission was significantly shorter in the surfactant group than in the control group.\n Surfactant replacement therapy, if started within 6 hours after birth, improves oxygenation and reduces the incidence of air leaks, severity of pulmonary morbidity, and hospitalization time of term infants with MAS.", "To compare the effects of patient-initiated, pressure-regulated, volume-controlled ventilation (PRVC) with pressure-preset intermittent mandatory ventilation (IMV) in neonates with respiratory failure.\n Randomised, prospective study.\n Intensive care unit (14 beds) in a 300-bed paediatric teaching hospital.\n 60 neonates with respiratory distress syndrome (RDS) or congenital pneumonia, weighing < 2500 g and requiring mechanical ventilation.\n Ventilatory support until extubation via either IMV (n = 30) or PRVC (n = 27). In PRVC, the tidal volume (VT) was preset and pressure-controlled breaths delivered with peak inspiratory pressure values adapted to achieve the preset VT.\n Main outcome measures were duration of ventilation and incidence of bronchopulmonary dysplasia (BPD). Pulmonary air leaks and intraventricular haemorrhage (IVH) were considered major adverse effects. Demographic data, ventilation parameters and arterial/alveolar oxygen tension ratio were similar at randomisation. Duration of ventilation and incidence of BPD were not decreased by the use of PRVC. Air leaks occurred in 3 neonates in the PRVC group and in 7 babies treated with IMV (NS). The incidence of IVH grade > II was lower in babies treated with PRVC (p < 0.05). In a subgroup of neonates weighing < 1000 g, the duration of ventilation and incidence of hypotension were reduced in the PRVC group (p < 0.05).\n Patient-initiated, pressure-regulated, volume-controlled ventilation can be safely used in neonates and may contribute to a lower incidence of complications." ]	Caution should be exercised in applying these results to modern neonatal intensive care, because the studies included in this review were conducted prior to the introduction of antenatal steroids, post natal surfactant and the use of synchronised modes of ventilatory support. Most of the participants had single pathology (HMD) and no studies examined the effects of IT on newborns ventilated for other reasons such as meconium aspiration and congenital heart disease (lungs with normal compliance). However, the increased rates of air leaks and deaths using long ITs are clinically important; thus, infants with poorly compliant lungs should be ventilated with a short IT.
CD000035	[ "9085210", "9692416" ]	[ "Betamimetics in fetal distress: randomised controlled trial.", "Effect of dexamethasone and betamethasone on fetal heart rate variability in preterm labour: a randomised study." ]	[ "The objective of the study was to investigate if a single dose of Hexoprenaline administered to patients diagnosed as having fetal distress improves neonatal outcome and whether there are any side effects and complications related to hexoprenaline injection. Patients with fetal distress diagnosed by electronic fetal heart rate monitoring with a gestational age of 35 weeks or more in active labor were eligible. Once the decision to deliver the patient by Cesarean section was made, patients were approached and randomised by sealed opaque envelopes to hexoprenaline or control groups. Ten micrograms of hexoprenaline were administered intravenously to study patients. Main outcomes were cord blood gas values, Apgar scores, the need for resuscitation and admission to intensive care. There were no statistically significant differences in the main outcome measures between the two groups. Fewer babies in the hexoprenaline group had a pH of < 7.2 and a base excess of < -10, but this was not statistically significant. The fetal heart rate pattern was improved in significantly more patients after hexoprenaline administration than controls. In conclusion, despite the statistically significant improvement in fetal heart rate tracings, Apgar scores and blood gas values showed only a trend towards improvement in the hexoprenaline group.", "To compare the effects of betamethasone and dexamethasone on fetal heart rate in appropriately grown fetuses.\n Eighty-two pregnant women (97 fetuses) with preterm labour were randomly allocated to receive betamethasone (n=42) or dexamethasone (n=40) for fetal lung maturation in a nonblinded fashion. Computerised cardiotocogram (CTG) parameters were compared before, during and after treatment.\n A decrease in fetal heart rate variability was found with betamethasone but no significant changes were found with dexamethasone. Fetal heart rate variability returned to pre-treatment values within a week after cessation of treatment with betamethasone. Neonatal outcome was similar in the two groups.\n These findings might prove useful in the management of compromised fetuses with decreased fetal heart rate variability in which the CTG should be used together with other parameters to assess fetal wellbeing during corticosteroid treatment. Dexamethasone may be preferable as the drug of choice since it was associated with significantly less alteration in fetal heart rate variability compared with betamethasone." ]	Betamimetic therapy appears to be able to reduce the number of fetal heart rate abnormalities and perhaps reduce uterine activity. However, there is not enough evidence based on clinically important outcomes to evaluate the use of betamimetics for suspected fetal distress.
CD004208	[ "8444226", "1444555" ]	[ "Randomised controlled trial of albumin infusion in ill preterm infants.", "Randomised controlled trial of colloid infusions in hypotensive preterm infants." ]	[ "We assessed the effect of albumin infusion on weight loss and ventilation requirement in sick premature infants. Thirty infants, median gestational age 29 weeks, were entered into a randomised controlled trial, at a median of 2 days of age. The infants, all with an albumin level < or = 30 g/l, received either 5 ml/kg of 20% albumin or 5 ml/kg of their maintenance fluids (placebo), both given as part of the total daily fluid requirement. The response to the infusion was assessed by comparing two periods; 12 h immediately prior to the infusion and 12-24 h after the infusion. Albumin infusion was associated with a significant increase in albumin level and a significant reduction in weight, but in the placebo group there was a significant increase in weight. There were, however, no significant changes in the peak inspiratory pressure in response to either infusion. There was only a modest reduction (< 15%) in the inspired oxygen concentration, which occurred in both groups, but reached statistical significance only following the albumin infusion. We conclude that our results suggest that albumin infusion in \"hypoalbuminaemic\" sick preterm infants is unlikely to alter their respiratory status.", "Colloid infusions are often given to treat hypotension in preterm infants. The aim of this work was to assess whether it was the amount of protein or the volume of the colloid infused which accounted for the observed increase in blood pressure. Sixty preterm infants were randomised (20 in each group) to receive 5 ml/kg 20% albumin, 15 ml/kg fresh frozen plasma, or 15 ml/kg 4.5% albumin. All infusions were given at a rate of 5 ml/kg/hour in addition to maintenance fluids. The infants were randomised when hypotensive (systolic blood pressure less than 40 mm Hg for two hours). There was no significant difference in the blood pressure of the three groups before or one hour after beginning the infusion. The mean increase in blood pressure one hour after completing the infusion, however, was significantly lower in infants receiving 20% albumin: 9% compared with 17% in the group receiving 4.5% albumin, and 19% in the group receiving fresh frozen plasma. It is concluded that the volume infused rather than albumin load is important in producing a sustained increase in blood pressure." ]	There is a lack of evidence from randomised trials to determine whether the routine use of albumin infusion in preterm neonates with low serum albumin reduces mortality or morbidity and no evidence to assess whether albumin infusion is associated with significant side effects. There is a need for good quality, double-blind randomised controlled trials to assess the safety and efficacy of albumin infusions in preterm neonates with low serum albumin.
CD008819	[ "3883876" ]	[ "Varicose veins: optimum compression following sclerotherapy." ]	[ "There is uncertainty regarding the most satisfactory technique of lower limb compression following sclerotherapy for varicose veins. We have compared a standard bandaging technique with a high pressure compression stocking in a randomised trial. Efficacy was judged on the success of injections, complications of the treatment and patient satisfaction. In the stockinged legs 144 of 156 injections were successful, compared with 117 of 147 in the bandaged group (P less than 0.001) (Chi squared). The incidence of superficial thrombophlebitis was also reduced in the stocking group. In addition, the stocking technique costs less in materials than conventional bandaging. We would recommend compression stockings for evaluation in sclerotherapy of varicose veins." ]	There is insufficient, high quality evidence to determine whether or not compression stockings are effective as the sole and initial treatment of varicose veins in people without healed or active venous ulceration, or whether any type of stocking is superior to any other type. Future research should consist of a large RCT of participants with trunk varices either wearing or not wearing compression stockings to assess the efficacy of this intervention. If compression stockings are found to be beneficial, further studies assessing which length and pressure is the most efficacious could then take place.
CD002788	[ "9842809", "9926179", "16243994", "9257203", "8872689", "9195356", "16492856", "12699517", "8610912", "10536557", "1616158", "7772357", "11090730", "10386278", "7902034", "11407293", "9019175", "8001208", "8738686", "9849280", "9483596", "8949806", "11737185", "8832448", "10553857", "9389261", "1389845", "16517330" ]	[ "Rocuronium versus succinylcholine: are they equally effective during rapid-sequence induction of anesthesia?", "A large simple randomized trial of rocuronium versus succinylcholine in rapid-sequence induction of anaesthesia along with propofol.", "Rocuronium versus succinylcholine for rapid sequence induction of anesthesia and endotracheal intubation: a prospective, randomized trial in emergent cases.", "Double-blind comparison of two doses of rocuronium and succinylcholine for rapid-sequence intubation.", "A mixture of mivacurium and rocuronium is comparable in clinical onset to succinylcholine.", "Rocuronium versus succinylcholine for rapid-sequence induction using a variation of the timing principle.", "Rocuronium is not associated with more vocal cord injuries than succinylcholine after rapid-sequence induction: a randomized, prospective, controlled trial.", "Rocuronium combined with i.v. lidocaine for rapid tracheal intubation.", "Comparison of rocuronium and mivacurium to succinylcholine during outpatient laparoscopic surgery.", "Effect of rocuronium compared with succinylcholine on intraocular pressure during rapid sequence induction of anaesthesia.", "Evaluation of the endotracheal intubating conditions of rocuronium (ORG 9426) and succinylcholine in outpatient surgery.", "Pharmacodynamics of rocuronium with and without prior administration of succinylcholine.", "Rocuronium versus succinylcholine-atracurium for tracheal intubation and maintenance relaxation during propofol anesthesia.", "Intraocular pressure changes during rapid sequence induction and intubation: a comparison of rocuronium, atracurium, and succinylcholine.", "Comparison of rocuronium, succinylcholine, and vecuronium for rapid-sequence induction of anesthesia in adult patients.", "Effectiveness and safety of rocuronium-hypnotic sequence for rapid-sequence induction.", "[Intubation requirements after rocuronium and succinylcholine].", "Different priming techniques, including mivacurium, accelerate the onset of rocuronium.", "Comparison of intubating conditions after rocuronium and suxamethonium following \"rapid-sequence induction\" with thiopentone in elective cases.", "Comparison of rocuronium and suxamethonium for use during rapid sequence induction of anaesthesia.", "Onset of neuromuscular blockade and intubating conditions one minute after the administration of rocuronium in children.", "Influence of induction technique on intubating conditions after rocuronium in adults: comparison with rapid-sequence induction using thiopentone and suxamethonium.", "The effect of rocuronium on intraocular pressure: a comparison with succinylcholine.", "Rocuronium priming of atracurium-induced neuromuscular blockade: the use of short priming intervals.", "Visual estimation of onset time at the orbicularis oculi after five muscle relaxants: application to clinical monitoring of tracheal intubation.", "Comparison of suxamethonium and different combinations of rocuronium and mivacurium for rapid tracheal intubation in children.", "Comparison of intubating conditions after administration of Org 9246 (rocuronium) and suxamethonium.", "Is there an ideal approach for rapid-sequence induction in hypertensive patients?" ]	[ "The purpose of our study was to assess the onset and quality of muscle paralysis and intubation conditions with succinylcholine (Sch) or rocuronium (Roc) during rapid-sequence induction. Patients were randomly assigned to receive thiopental (5 mg/kg) and Sch (1.5 mg/kg) or thiopental (5 mg/kg) and Roc (1.2 mg/kg). The anesthesiologists performing the endotracheal intubation were blinded by standing with their back to the patient. Thirty seconds after drug administration, laryngoscopy was performed. Intubating conditions were scored, the clinical onset of apnea was noted, and a train-of-four monitor recorded data. All patients were ASA physical status I-III and scheduled for emergency procedures; both groups were demographically similar. Thirteen patients received Roc and 13 received Sch. There was no significant difference between the two groups in the number of patients receiving excellent intubating scores (P = 0.41) or in the combined number of patients receiving good and excellent scores (P = 1.0). There was no significant difference in time of onset of apnea for Sch (22+/-13 s) versus Roc (16+/-8s). The return of the first twitch response was significantly faster with Sch (5.05+/-2.5 min) compared with Roc (17.3+/-21.7 min) (P = 0.0001).\n In pediatric patients scheduled for emergency surgery, thiopental 5 mg/kg and rocuronium 1.2 mg/kg provided conditions for the completion of intubation in <60 s comparable to those provided by thiopental 5 mg/kg and succinylcholine 1.5 mg/kg. We conclude that rocuronium is a reasonable substitute for succinylcholine in children for rapid-sequence intubation when a rapid return to spontaneous respiration is not desired.", "Rocuronium has an onset of action more rapid than other non-depolarizing neuromuscular blocking agents, but it is unclear whether it and succinylcholine give equivalent intubating conditions during rapid-sequence induction of anaesthesia. We performed this study to answer the question--are there clinically relevant differences between the use of rocuronium and succinylcholine to secure acceptable intubating conditions during rapid-sequence induction of anaesthesia with propofol?\n Anaesthesia was induced using propofol 2.5 mg/kg in 349 ASA physical status grade I-IV patients who were undergoing either elective or emergency surgery. Propofol was followed immediately by either rocuronium 0.6 or 1 mg/kg or succinylcholine 1.0 mg/kg (randomly selected). Fifty seconds after the end of muscle relaxant injection laryngoscopy was performed and intubating conditions were graded by an experienced anaesthetist blind to the muscle relaxant allocation. This study design was selected so that a 10% difference in clinically acceptable intubating conditions between drugs would be detectable.\n In this setting rocuronium 1.0 mg/kg provided superior intubating conditions compared with rocuronium 0.6 mg/kg. The incidence of clinically acceptable intubating conditions with rocuronium 1.0 mg/kg and succinylcholine 1.0 mg/kg was 93.2% and 97.1% respectively, the difference being -3.9% (95% C.I. -9.7% to 1.9%).\n Rocuronium 1.0 mg/kg given along with propofol in a rapid-sequence induction of anaesthesia is clinically equivalent to succinylcholine 1.0 mg/kg.", "When anesthesia is induced with propofol in elective cases, endotracheal intubation conditions are not different between succinylcholine and rocuronium approximately 60 s after the injection of the neuromuscular relaxant. In the present study, we investigated whether, in emergent cases, endotracheal intubation conditions obtained at the actual moment of intubation under succinylcholine differ from those obtained 60 s after the injection of rocuronium. One-hundred-eighty adult patients requiring rapid sequence induction of anesthesia for emergent surgery received propofol (1.5 mg/kg) and either rocuronium (0.6 mg/kg; endotracheal intubation 60 s after injection) or succinylcholine (1 mg/kg; endotracheal intubation as soon as possible). The time from beginning of the induction until completion of the intubation was shorter after the administration of succinylcholine than after rocuronium (median time 95 s versus 130 s; P < 0.0001). Endotracheal intubation conditions, rated with a 9-point scale, were better after succinylcholine administration than after rocuronium (8.6 +/- 1.1 versus 8.0 +/- 1.5; P < 0.001). There was no significant difference in patients with poor intubation conditions (7 versus 12) or in patients with failed first intubation attempt (4 versus 5) between the groups. We conclude that during rapid sequence induction of anesthesia in emergent cases, succinylcholine allows for a more rapid endotracheal intubation sequence and creates superior intubation conditions compared with rocuronium.", "To compare the pharmacodynamics of two commonly recommended doses of rocuronium bromide (0.7 mg/kg and 0.9 mg/kg) and succinylcholine (1.5 mg/kg) when used for rapid-sequence intubation.\n Prospective, double-blind, randomized study.\n Operating rooms at a university hospital.\n 45 ASA physical status I and II adult patients scheduled for elective surgeries under general anesthesia.\n Nonpremedicated patients were anesthetized with fentanyl 2 mcg/kg followed by thiopental sodium 4 to 5 mg/kg and muscle relaxant using rapid-sequence technique. Group 1 (n = 15) received rocuronium bromide 0.7 mg/kg. Group 2 (n = 16) received rocuronium bromide 0.9 mg/kg, and Group 3 (n = 14) received succinylcholine 1.5 mg/kg. Intubation was performed 60 seconds after the administration of muscle relaxant.\n The case of intubation was scored using a scale of 1 to 4. Blood pressure and heart rate were measured beginning one minute before induction of anesthesia up to 5 minutes after intubation. Intubation scores were similar in groups 2 and 3 and were noted as good or excellent in all patients. Group 1 displayed a significantly lower intubation score than the other two groups; 60% were rated as poor. No significant differences in hemodynamic data were seen among the three groups.\n Rocuronium bromide at a dose of 0.9 mg/kg provides intubating conditions similar to succinylcholine 1.5 mg/kg at 1 minute. Intubating conditions at 1 minute following a 0.7 mg/kg dose of rocuronium are not as good as those following a 0.9 mg/kg dose of rocuronium or a 1.5 mg/kg dose of succinylcholine.", "To compare the clinical onset and duration of a combination of mivacurium and rocuronium with succinylcholine, and to determine the efficacy of this mixture for rapid tracheal intubation.\n Observer-blind prospective study.\n Teaching hospital.\n 70 ASA status I and II patients having general anesthesia for elective surgery.\n After induction of general anesthesia, patients randomly received succinylcholine 1.0 mg/kg, rocuronium 0.6 mg/kg, or a combination of rocuronium 0.6 mg/kg and mivacurium 0.15 mg/kg. Evoked muscular response at the adductor pollicis was measured by mechanomyography. The time from injection of muscle relaxant(s) to ablation of T1 (clinical onset) and recovery of T1 to 25% of control height (clinical duration) was recorded. Intubating conditions 45 seconds after administration of muscle relaxants were assessed. There was no significant difference in clinical onset time between succinylcholine (mean +/- SD, 47.4 +/- 6.5 seconds) and the combination of mivacurium-rocuronium (51.2 +/- 13.4 seconds). Intubating conditions with mivacurium-rocuronium were comparable to those of succinylcholine. The clinical duration of rocuronium 0.6 mg/kg (38.9 +/- 12.3 minutes) was prolonged by the addition of mivacurium (49.0 +/- 9.6 minutes).\n This combination of mivacurium and rocuronium is comparable to succinylcholine in both clinical onset time and quality of intubating conditions. When rapid onset of dense neuromuscular blockade and intermediate clinical duration is desirable, this mixture may be an acceptable alternative to succinylcholine.", "To determine if, using a variation of the \"timing\" principle, 0.6 mg/kg of rocuronium can achieve an onset time and intubating conditions similar to those achieved with succinylcholine.\n Prospective, randomized, double-blind clinical comparison.\n Operating room in a university medical center.\n 42 ASA physical status I and II patients undergoing general anesthesia for elective surgery.\n All patients were fitted with a Grass FT-10 force transducer attached to the thumb. Supramaximal stimulation was applied to the ulnar nerve with a variable current peripheral nerve stimulator. 22 patients (succinylcholine group) received a placebo bolus injection followed 20 seconds later by thiopental 4 to 5 mg/kg and succinylcholine 1 mg/kg; 20 additional patients (rocuronium group) received a bolus dose of rocuronium 0.6 mg/kg followed 20 seconds later by thiopental 4 to 5 mg/kg and a placebo bolus injection.\n We measured the onset time from administration of the muscle relaxant to 95% twitch reduction and assessed the quality of intubating conditions 60 seconds after the induction of anesthesia. There was a significant difference in the mean onset time of rocuronium (72 sec) versus succinylcholine (42 sec, p < 0.0001). However, there was no significant difference in intubating conditions 60 seconds after administration of thiopental.\n Rocuronium given 20 seconds prior to thiopental provides intubating conditions equivalent to thiopental-succinylcholine for rapid-sequence inductions, circumventing rocuronium's longer onset time to 95% neuromuscular blockade.", "Postoperative hoarseness (PH), sore throat (ST), and vocal cord injuries (VCI) are common complications after general anesthesia. Excellent endotracheal intubating conditions are associated with less laryngeal morbidity than good or poor intubating conditions. Thus, we tested the hypothesis that a rapid-sequence induction (RSI) with succinylcholine would lead to less PH and VCI than with rocuronium. In this prospective trial, 160 patients were randomized in 2 groups to receive thiopental 5.0 mg/kg, fentanyl 3.0 microg/kg, succinylcholine 1.0 mg/kg, or rocuronium 0.6 mg/kg during RSI. PH and ST were assessed at 24, 48, and 72 h after surgery, VCI were examined by stroboscopy in those patients who had PH >3 days. Excellent and clinically acceptable intubating conditions were significantly increased in the succinylcholine group compared with the rocuronium group: 57% versus 21% and 89% versus 59%, respectively (P < 0.001). The incidence and severity of PH, and VCI between the succinylcholine and the rocuronium groups did not differ significantly: PH: 50% versus 51% (P = 0.99) and VCI: 3% versus 1% (P = 0.98), respectively. Similar findings were found for ST, 39% versus 28% (P = 0.22), and postoperative myalgia, 39% versus 29% (P = 0.25), respectively. Intubating conditions were significantly better in the succinylcholine group compared with the rocuronium group. The incidence and severity of ST and myalgia were not increased in the patients receiving succinylcholine. However, the rate of PH and VCI was similar to the rocuronium group.", "Rocuronium (ORG 9426) has been shown to have an onset of action more rapid than other nondepolarizing neuromuscular blocking agents and to provide intubating conditions similar to those of succinylcholine 60-90 s after administration. We compared the intubating conditions and hemodynamic changes after the administration of rocuronium 0.6 mg kg(-1) and lidocaine 1.5 mg kg(-1) with rocuronium alone and succinylcholine 60 and 90 s after administration.\n One hundred and twenty-five adult patients of ASA physical status I or II scheduled for elective surgery were randomly divided into five groups. After propofol administration in all patients, patients in group Su (succinylcholine), group R60 (rocuronium) and group RL60 (rocuronium-lidocaine) were intubated within 60 s, while groups RL90 and R90 were intubated 90 s after the administration of rocuronium and succinylcholine. Laryngoscopy was performed and intubating conditions were graded by an experienced anesthetist blind to the muscle relaxant allocation.\n In this study, groups Su, RL60, R90 and RL90 had similar intubation scores, which were significantly better than that for group R60. Heart rate did not increase after intubation in groups Su, RL60 and RL90.\n The combination of lidocaine (1.5 mg kg(-1)) and low-dose rocuronium (0.6 mg kg(-1)) along with propofol is clinically equivalent to succinylcholine, improves intubating conditions in 60 s and effectively blocks increases in heart rate after intubation.", "Tracheal intubating conditions and neuromuscular effects of succinylcholine, rocuronium, and mivacurium were studied in 100 healthy women undergoing outpatient laparoscopic surgery. After a standardized fentanyl-thiopental induction, tracheal intubation was facilitated with succinylcholine 1 mg/kg in Groups I (n = 23) and II (n = 25), rocuronium 0.6 mg/kg in Group III (n = 27), or mivacurium 0.2 mg/kg in Group IV (n = 25). If clinically indicated, bolus doses of rocuronium 5-10 mg (Groups I and III) or mivacurium 2-4 mg (Groups II and IV) were administered during the maintenance period. Anesthesia was maintained with desflurane and nitrous oxide 60% in oxygen. At the end of the surgery, residual neuromuscular block was reversed with edrophonium 0.5 mg/kg and atropine 10 micrograms/kg, if needed. The neuromuscular function was assessed using electromyography with a train-of-four mode of stimulation every 10 s at the wrist. Intubating conditions 90 s after succinylcholine and rocuronium were significantly better than after mivacurium. The onset time (from the end of injection until 95% suppression of the first twitch [T1]) for succinylcholine (63 +/- 21 s and 62 +/- 17 s in Groups I and II, respectively) were significantly shorter than for rocuronium (158 +/- 76 s) or mivacurium (210 +/- 93 s). Moreover, the onset times for rocuronium were significantly shorter than mivacurium. The recovery times (of T1 to 25% of the control value) were significantly shorter with succinylcholine and mivacurium than rocuronium. Significantly fewer patients needed reversal of residual neuromuscular blockade after mivacurium compared to rocuronium. One patient in Group I and six patients in Group IV displayed erythema on the upper body. Postoperative myalgia were experienced by 16% of the patients in Groups I and II compared to none in Groups III and IV. There was on difference in the incidence of postoperative nausea and vomiting among the four groups. In conclusion, rocuronium appears to be an acceptable alternative to succinylcholine for tracheal intubation. However, rocuronium's longer duration of action increases the need for reversal drugs. When rapid tracheal intubation is unnecessary, mivacurium is also an acceptable alternative to succinylcholine and is associated with a more rapid spontaneous recovery than rocuronium.", "We have compared the effect of rocuronium and succinylcholine on intraocular pressure (IOP) during rapid sequence induction of anaesthesia using propofol and fentanyl, in a randomized double-blind study. We studied 30 adult patients, allocated to one of two groups. Anaesthesia was induced with fentanyl 2 micrograms kg-1 and propofol until loss of verbal response. This was followed by succinylcholine 1.5 mg kg-1 (group S; n = 15) or rocuronium 0.9 mg kg-1 (group R; n = 15). Laryngoscopy was performed 60 s later. IOP, mean arterial pressure (MAP) and heart rate (HR) were measured before induction, immediately before intubation and every minute after intubation for 5 min. A Keeler Pulsair air impulse tonometer was used to measure IOP and the mean of two readings obtained in the right eye at each measurement time was recorded. Intubating conditions were evaluated according to a simple scoring system. IOP in the succinylcholine group was significantly greater than that in the rocuronium group (mean 21.6 (SEM 1.4) mm Hg vs 13.3 (1.4) mm Hg; P < 0.001). Intubating conditions were equally good in both groups. We conclude that with rapid sequence induction of anaesthesia using propofol and fentanyl, rocuronium did not cause as great an increase in IOP as succinylcholine and may be an alternative in open eye injury cases.", "The time-course of action and tracheal intubating conditions of rocuronium and succinylcholine under intravenous anesthesia with propofol, alfentanil, and nitrous oxide were studied in 30 patients undergoing outpatient surgery. The neuromuscular effects of both drugs were quantified by recording the indirectly evoked twitch response of the adductor pollicis muscle after ulnar nerve stimulation (0.1 Hz, 0.2 ms supramaximal stimuli). Patients were given either 0.6 mg/kg rocuronium (n = 20) or 1 mg/kg succinylcholine (n = 10) intravenously. Sixty seconds after the administration of the muscle relaxant, the trachea was intubated and the intubating conditions were scored by a \"blinded\" assessor. Intubating conditions were not different (P = 0.34) between the rocuronium and succinylcholine groups. The onset and duration of neuromuscular blockade were shorter with succinylcholine than with rocuronium. The depression of the twitch response to 5% of control value occurred in 0.8 +/- 0.1 min with 1 mg/kg succinylcholine and 1.2 +/- 0.5 min with 0.6 mg/kg rocuronium (P less than 0.01). The recovery of the twitch response to 25%, 75%, and 90% of its control value was shorter after succinylcholine (P less than 0.001) and occurred at 8.1 +/- 2.6, 10.3 +/- 3.9, 11.3 +/- 4.6 and 25.3 +/- 5.0, 33.1 +/- 5.9, 36.1 +/- 6.3 min after succinylcholine and rocuronium, respectively. Also the time required for spontaneous recovery from 25% to 75% of the control twitch response was significantly shorter (P less than 0.001) after succinylcholine (2.2 +/- 1.4 min) than after rocuronium (7.8 +/- 2.1 min). It is concluded that in spite of the pharmacodynamic differences between succinylcholine and rocuronium, the intubating conditions after administration of both compounds are similar and develop at the same rate.", "To compare succinylcholine (S) and rocuronium (R) used for endotracheal intubation, and to assess the possible action of S on subsequently administered R.\n Double-blind, randomized, phase III study.\n University Medical Center.\n 24 ASA physical status I and II patients, ages 28 to 65, undergoing general anesthesia for abdominal procedures.\n Double-blind administration of R 600 mcg/kg (Group A) or S 1 mg/kg was achieved with open label R 150 mcg/kg. Standardized general anesthetic technique with sodium thiopental, fentanyl, and nitrous oxide in oxygen was administered.\n Neuromuscular junction was tested by ulnar nerve stimulation and mechanomyograph. Intubation was attempted at 80% first twitch depression of train-of-four. Heart rate and blood pressure were recorded throughout. Onset times were 74 +/- 37 seconds for S and 130 +/- 46 seconds for R. Intubation times were 76 +/- 29 seconds for S and 85 +/- 23 seconds for R (no significant difference). Good to excellent intubation conditions were achieved in both groups. S given prior to R decreased onset time and increased duration of R, when compared with R given alone. No drug related cardiovascular events were noted.\n Rapid intubation conditions can be obtained after both S and R. Given its overall safety profile, R can be used when S is contraindicated, or in healthy patients with no apparent difficult airway, when procedures are expected to last more than 25 minutes.", "To compare the onset and offset time (clinical duration), and intubating conditions obtained with rocuronium bromide 0.6 mg/kg and succinylcholine 1.0 mg/kg after induction with propofol and fentanyl; and to compare rocuronium with atracurium for maintenance during propofol anesthesia.\n Prospective, open-label, parallel group comparative, randomized study.\n Operating rooms of a university hospital.\n 30 ASA physical status I and II adult patients scheduled for elective surgeries with general anesthesia.\n Patients premedicated with midazolam 2 mg were anesthetized with fentanyl 2 microg/kg followed by propofol 2.5 mg/kg and muscle relaxants. Group 1 (n = 15) received succinylcholine 1.5 mg/kg and Group 2 (n = 16) received rocuronium bromide 0.6 mg/kg. Intubation was performed 60 seconds after the administration of muscle relaxant. Patients in Group 1 received atracurium and patients in Group 2 received rocuronium for maintenance if required.\n The ease of intubation was scored using a scale of 1 to 4. Onset and offset time monitored with evoked twitch response of the adductor pollicis were recorded.\n Intubation was successful in all patients and there was no difference in scores between the two groups. Although onset time was shorter with succinylcholine than with rocuronium, neuromuscular blockade was successfully antagonized in both groups, and the recovery profile was not different between the two groups.\n Rocuronium bromide at a dose of 0.6 mg/kg, when used with propofol and fentanyl for induction, provides intubating conditions similar to succinylcholine 1.0 mg/kg at 1 minute. The actual onset time and offset time, however, are significantly longer with rocuronium. There was no difference between atracurium and rocuronium as a maintenance drug. Rocuronium is suitable for surgical procedures greater than 30 minutes, eliminating the need for an additional relaxant to succinylcholine.", "To compare changes in intraocular pressure (IOP) during rapid sequence induction and intubation following rocuronium, succinylcholine, and atracurium.\n Open-label, prospective, randomized study.\n Operating room at the Eye Foundation Hospital (University of Alabama at Birmingham)\n 45 ASA physical status I, II, and III patients, aged 18 to 65 years, scheduled for elective eye surgery with general anesthesia.\n Anesthesia was rapidly induced in unpremedicated patients with a fixed combination of midazolam 0.025 mg/kg, alfentanil 0.025 mg/kg, and propofol 1.5 mg/kg. Intubation was performed, as clinically indicated, approximately 60 seconds following administration of rocuronium 0.6 mg/kg, atracurium 0.5 mg/kg, or succinylcholine 1 to 1.5 mg/kg.\n Intraocular pressure was measured before induction of anesthesia (baseline), following anesthesia induction and administration of muscle relaxant (before intubation), and after intubation. The percent change in IOP from baseline was significantly decreased in the rocuronium group compared with the succinylcholine group (p = 0.046) before intubation. This trend continued after intubation, but the difference was no longer significant (p = 0.070). Intubation scores for rocuronium and succinylcholine groups were similar, and both scores were superior to that for the atracurium group (p = 0.002).\n Intraocular pressure can be controlled during emergency induction of anesthesia and intubation with adequate depth of anesthesia and muscle relaxation. Rocuronium, succinylcholine, and atracurium all provided sufficient muscle relaxation to achieve successful intubation and no increase in IOP. However, rocuronium 0.6 mg/kg provided significantly better intubating conditions compared with atracurium, and it resulted in a significantly greater decrease in IOP compared with baseline than succinylcholine.", "Succinylcholine has been the agent of choice when clinical conditions require emergency airway protection during a rapid-sequence induction of anesthesia. Rocuronium, a new nondepolarizing muscle relaxant with a brief onset of action, but devoid of the adverse reactions associated with succinylcholine, may be an alternative to succinylcholine. To test this hypothesis, the authors compared rocuronium with succinylcholine and vecuronium for rapid-sequence induction of anesthesia.\n Fifty patients, ASA 1-3, were randomly designated to receive one of three intravenous doses of rocuronium (0.6, 0.9, and 1.2 mg/kg), vecuronium (0.1 mg/kg), or succinylcholine (1.0 mg/kg). Patients were premedicated with midazolam and fentanyl, and received 2-7 mg/kg thiopental for induction of anesthesia. Sixty seconds after receiving a muscle relaxant, intubation of the trachea was attempted by a clinician who was blinded to the muscle relaxant administered. Neuromuscular monitoring was established before administration of the muscle relaxant. The time from injection of muscle relaxant until complete ablation of T1 (onset) and recovery of T1 to 25% (duration) were recorded. Tracheal intubating conditions were evaluated, and the presence or absence of fasciculations was noted.\n Onset times for patients receiving 0.9 mg/kg (75 +/- 28 s) and 1.2 mg/kg rocuronium (55 +/- 14 s), and succinylcholine (50 +/- 17 s) were similar. Onset times for the groups given 0.6 mg/kg rocuronium (89 +/- 33 s) and vecuronium (144 +/- 39 s) were significantly longer. Clinical duration of action was longest with 1.2 mg/kg rocuronium, similar with 0.6 and 0.9 mg/kg rocuronium, and vecuronium, and least with succinylcholine.\n There is a dose-dependent decrease in onset time with rocuronium. The onset times for the two larger doses of rocuronium were similar to that for succinylcholine, but clinical duration of action with rocuronium was significantly longer. The brief onset time achieved with rocuronium indicates that administration of 0.9-1.2 mg/kg is an acceptable alternative to succinylcholine for rapid-sequence induction of anesthesia.", "Either succinylcholine or rocuronium administered after a hypnotic is the current technique for rapid-sequence induction. It is assumed that rocuronium administered before a hypnotic (Rocuronium-hypnotic sequence) may equally provide an acceptable intubation condition as well as a shorter period of apnea in rapid-sequence induction. We designed a prospective, randomized study to evaluate the effectiveness and safety of the technique in a similar rapid-sequence induction.\n Ninety adult patients receiving elective surgeries were enrolled in this study. In all patients the procedure in the study began with i.v. injection of fentanyl 2 micrograms/kg, followed by preoxygenation with 100% O2 for 2 min. Afterward, the patients were randomly allocated to 3 groups with each group consisting of 30 patients. In Rocuronium-thiopental (Ro-Th) group the patients received rocuronium 0.6 mg/kg and then thiopental 5 mg/kg; in Th-Ro group the patients received thiopental 5 mg/kg and then rocuronium 0.6 mg/kg; and in Thiopental-Succinylcholine (Th-Sx) group, the control group, the patients received thiopental 5 mg/kg and then succinylcholine 1 mg/kg. Laryngoscopy and endotracheal intubation were performed 60 s after the injection of the muscle relaxant. The intubation condition, the apneal time before laryngoscopy, the intubation time, and total apneal time were investigated and compared. Presence of injection pain, sense of paralysis, SpO2 less than 95% during induction, and any unexpected adverse event were also recorded.\n Six patients (1 in Ro-Th group, 2 in Th-Ro group, and 3 in Th-Sx group, respectively) were excluded from the study. The intubation conditions were acceptable in all patients of three groups who completed the study, and as to excellent intubation condition there was no difference between the three groups. In Ro-Th group both the apneal time before laryngoscopy (32.4 +/- 5.4 s) and total apneal time (48.5 +/- 11.0 s) were the shortest. Th-Ro group (53.2 +/- 5.8 and 67.5 +/- 8.3 s, respectively) and Th-Sx group (54.4 +/- 5.8 and 68.4 +/- 7.7 s, respectively) were similar in both aspects. With respect to intubation time there was no significant difference among the three groups. Five patients in Ro-Th group and one patient in Th-Sx group felt mild injection pain. Three patients in Ro-Th group were noted to have diminished breathing during induction, which was not recalled during enquiry in the postoperative visit. One patient in Ro-Th group saw a fall of SpO2 down below 95% (94% the minimal) during the apnea period.\n Compared with traditional hypnotic-rocuronium or hypnotic-succinylcholine sequence, rocuronium (0.6 mg)-thiopental sequence can provide a similar intubation condition but cause a much shorter apneal period in rapid-sequence induction. In carrying out recuronium-thiopental sequence induction, maintaining a patent infusion line is essential to avoid drug precipitation and awareness of muscular weakness as a result of ill-timed action of thiopental.", "Rocuronium is a new non-depolarising steroidal muscle relaxant with a short onset time. The present study was undertaken to compare intubating conditions as well as onset and clinical duration of a single dose of 0.6 mg/kg (2 x ED95) with a single dose of 1 mg/kg suxamethonium (3 x ED95).\n After obtaining informed consent and approval of the Ethics Committee, 40 adult patients (ASA I-III) participated in this study. After premedication with oxazepam, anaesthesia was induced with fentanyl and propofol and maintained with propofol, N2O and supplements of fentanyl as needed. Muscular relaxation was assessed by EMG recording of adductor pollicis muscle after supramaximal single twitch stimulation of the ulnar nerve every 10 s. Patients were allocated randomly to receive either rocuronium 0.6 mg/kg or suxamethonium 1 mg/kg. The following parameters were measured: intubating conditions 60 s after injection, onset time and clinical duration of neuromuscular block, % block at intubation, heart rate, blood pressure and arterial oxygen saturation.\n (mean +/- SD). Intubating conditions after rocuronium and suxamethonium were found to be clinically acceptable (excellent or good) in 90% of patients, though there was only a partial blockade of the adductor pollicis muscle with rocuronium (71 +/- 23%) compared to suxamethonium (95 +/- 14%) (p < 0.05). The onset time and clinical duration of relaxation was shorter after suxamethonium (p < 0.05) and occurred at 0.8 +/- 0.2, 7 +/- 2.1 and 3.2 +/- 1.3, 29 +/- 11 min after suxamethonium and rocuronium respectively.\n At a dosage of 0.6 mg/kg, rocuronium has an onset time of about 3 min and a clinical duration of relaxation of nearly half an hour. These data are supported by various studies, while others show shorter times, probably due to different monitoring techniques. In spite of the pharmacodynamic differences between suxamethonium and rocuronium, the intubating conditions after administration of both compounds are comparable and develop at the same rate.", "Different priming sequences of equipotent doses of rocuronium and mivacurium on the onset of maximum neuromuscular block and intubating conditions were compared with those obtained after succinylcholine. During thiopentone-fentanylnitrous oxide anaesthesia, 70 patients were randomly assigned into seven groups. Group I received mivacurium 0.15 mg.kg-1 as a single bolus dose. Group II received a priming dose of mivacurium 0.015 mg.kg-1 followed three minutes later by mivacurium 0.135 mg.kg-1. Group III received rocuronium 0.6 mg.kg-1 as a single bolus dose, and Group IV received an initial dose of rocuronium 0.06 mg.kg-1 followed by rocuronium 0.54 mg.kg-1. Group V received a priming dose of mivacurium 0.015 mg.kg-1 followed by rocuronium 0.54 mg.kg-1. Group VI received an initial dose of rocuronium 0.06 mg.kg-1 followed by mivacurium 0.135 mg.kg-1. Group VII received succinylcholine 1.0 mg.kg-1. Groups I, III, and VII received a placebo injection before the administration of the neuromuscular blocking drug. Additional thiopentone 2 mg.kg-1 iv was given 30 sec before intubation. Onset times (mean (95% confidence interval)) after priming a rocuronium block with either rocuronium (73 (57-90) sec) or mivacurium (58 (47-69) sec) were similar to those after succinylcholine (54 (40-68) sec), and were shorter (P < 0.01) than that observed in other groups. Intubating conditions were not different between the groups. The duration of neuromuscular block was shortest with succinylcholine. It is concluded that priming a rocuronium block with either mivacurium or rocuronium resulted in a neuromuscular block comparable to that of succinylcholine in both the onset of action and intubating conditions.", "Rocuronium (Org 9426) was shown to have the fastest onset of action of all currently available non-depolarizing neuromuscular blocking drugs and to provide intubating conditions similar to those of suxamethonium 60 to 90 s after administration. We compared the intubating conditions after rocuronium and suxamethonium following rapid-sequence induction of anaesthesia.\n Fifty unpremedicated patients of ASA physical status I or II, scheduled for elective surgery were studied. Anaesthesia was induced with thiopentone 6 mg kg-1 followed randomly by suxamethonium 1 mg kg-1 or rocuronium 0.6 mg kg-1 and, 45 s later, intubation was commenced. Muscle fasciculations, intubating conditions and intubation time, haemodynamic variables and oxygenation were assessed.\n Intubation time did not differ between suxamethonium (9.8 +/- 2.2 s) (mean +/- SD) and rocuronium (10.5 +/- 2.9 s), respectively. Intubating conditions were clinically acceptable (good or excellent) in all patients given suxamethonium and in 96% of the patients given rocuronium. However, the condition of the vocal cords was better (P < 0.05) and diaphragmatic response to intubation was less pronounced with suxamethonium (P < 0.05). Changes in heart rate and arterial blood pressure were similar in both groups.\n The authors conclude that rocuronium is a suitable alternative to suxamethonium for rapid tracheal intubation even under unsupplemented thiopentone anaesthesia, at least in elective, otherwise healthy patients. Its use for rapid-sequence induction under emergency conditions, however, needs further investigation.", "This study was designed to compare the tracheal intubating conditions during a rapid sequence induction of anaesthesia using rocuronium 0.6 (n = 61) or 1.0 mg.kg-1 (n = 130) or suxamethonium 1.0 mg.kg-1 (n = 127) as the neuromuscular blocking drugs. Anaesthesia was induced with fentanyl 1-2 micrograms.kg-1 and thiopentone 5 mg.kg-1 (median dose) and intubating conditions were assessed 60s after the administration of the neuromuscular blocking drug by an observer unaware of which drug had been given. Intubating conditions were graded on a three-point scale as excellent, good or poor, the first two being considered clinically acceptable. The study was carried out in two parts. At the end of the first part a comparison between the two doses of rocuronium was carried out when at least 50 patients had been enrolled in each group. The results showed the intubating conditions to be significantly superior with the 1.0 mg.kg-1 dose of rocuronium (p < 0.01). Final comparison between the 1.0 mg.kg-1 doses of rocuronium and suxamethonium showed no significant difference in the incidence of acceptable intubations (96 and 97%, respectively). The incidence of excellent grade of intubations was, however, significantly higher with suxamethonium (80% vs. 65%; p = 0.02). It is concluded that rocuronium 1.0 mg.kg-1 can be used as an alternative to suxamethonium 1.0 mg.kg-1 as part of a rapid sequence induction provided there is no anticipated difficulty in intubation. The clinical duration of this dose of rocuronium is, however, 50-60 min.", "In a blinded randomized study intubating conditions were compared at one min following intravenous induction with propofol and either suxamethonium 1.0 mg.kg-1, or rocuronium 0.6 mg.kg-1. Onset time to maximal twitch depression, % block at one minute and clinical duration (time to 25% recovery) were measured. Sixty children undergoing elective tonsillectomy were recruited. Onset time [42s (SD 11s)] and clinical duration [3.3 min (SD 1.0 min)] in the suxamethonium group was significantly (P < 0.001) less than in the rocuronium group [92s (41s)] and [24.2 min (6.6 min)] respectively. The median twitch height at one minute for suxamethonium was 0% (range 0-8%) and significantly greater (P < 0.001) at 5% (range 0-22%) for rocuronium. Despite this there was no difference in the intubating conditions at one minute with 25 excellent/5 good in the suxamethonium group and 27 excellent/3 good in the rocuronium group. We conclude that rocuronium 0.6 mg.kg-1 gives optimal intubating conditions at one minute in children.", "We have assessed the effect of anaesthetic technique on intubating conditions after rocuronium 0.6 mg kg-1 in four groups (n = 25 each) of unpremedicated patients in whom anaesthesia was induced with either thiopentone 5 mg kg-1 or propofol 2.5 mg kg-1 alone, or supplemented with alfentanil 20 micrograms kg-1. Fifty control patients were anaesthetized with thiopentone followed by suxamethonium. Laryngoscopy was commenced at 45 s. Overall intubating conditions after rocuronium were similar to those after suxamethonium (good and excellent > or = 96%) only when alfentanil was part of the induction regimen. However, intubation time was similar in all five groups and averaged 55 (SD 3.2) s, and the tube could be passed through open vocal cords within 70 s. After rocuronium the response of the diaphragm to intubation was more pronounced in the two groups of patients not receiving alfentanil (P < 0.0001) and in patients anaesthetized using propofol with alfentanil (P < 0.01) than in the control group. Opioids (in doses equivalent to alfentanil 20 micrograms kg-1) constitute an integral part of an induction regimen containing rocuronium 0.6 mg kg-1, regardless of whether or not thiopentone or propofol is used, in order to achieve overall intubating conditions similar to those after suxamethonium.", "nan", "To evaluate the effects of priming doses of rocuronium on the duration of priming interval and on the outcome of priming sequence using rocuronium-atracurium combination.\n Three phase, randomized, controlled study.\n Inpatient anesthesia in a university hospital.\n 144 ASA physical status I and II patients, 19 to 57 years of age, weighing 50 to 90 kg, and undergoing low-risk elective surgery.\n Phase I, two equal groups (n = 12) of adult patients anesthetized with propofol, fentanyl, and nitrous oxide (N2O), received a priming dose of rocuronium 0.1 mg/kg or vecuronium 0.015 mg/kg. Phase II included six equal groups (n = 12): Groups 1, 2, and 3 received a priming dose of rocuronium 0.1 mg/kg and atracurium 0.42 mg/kg for intubation. The priming intervals were, respectively, 1, 1.5, or 2 minutes in Groups 1, 2, and 3. Groups 4, 5, and 6 received, respectively, a bolus dose of rocuronium 0.6 mg/kg, atracurium 0.5 mg/kg, or succinylcholine 1 mg/kg. Intubation was performed at maximum block. Phase III included four equal groups (n = 12). A priming dose of rocuronium 0.1 mg/kg (Group 1) or a placebo (Groups 2, 3, and 4) was given to awake patients. Anesthesia was induced during the one-minute priming interval. Intubating doses of atracurium 0.42 mg/kg, rocuronium 0.6 mg/kg, atracurium 0.5 mg/kg, or succinylcholine 1 mg/kg were given to Groups 1, 2, 3, and 4, respectively. Intubation was attempted 1 minute after intubating doses were administered.\n Adductor pollicis response to train-of-four stimulation was recorded mechanically in Phases I and II only. The priming interval after rocuronium 0.1 mg/kg was in the range of 1 to 2 minutes. Priming doses of rocuronium resulted in significant acceleration in the onset time of intubating doses of atracurium, irrespective of the duration of the priming interval. The onset times [mean (SD)] following rocuronium-atracurium sequence in Groups 1, 2, and 3 were, respectively, 67 (17), 73 (14), and 66 (18) seconds and were comparable with the onset of bolus doses of rocuronium and succinylcholine. In Phase II, good to excellent intubating conditions were obtained in 41% to 58% of patients included in Groups 1 through 5. Excellent to good intubating conditions were obtained in all patients (100%) who received succinylcholine. In Phase III, good to excellent intubating conditions were obtained in 91% of patients who received recuronium-atracurium sequence. Symptoms of muscle weakness were not reported.\n Priming doses of recuroniums 0.1 mg/kg reduce the priming interval to 1 minute, allow early induction of anesthesia, eliminate patient discomfort, and accelerate the onset time of altracurium with intubating conditions comparable with succinylcholine and rocuronium.", "The onset time of neuromuscular blockade at the adductor pollicis (AP) is different among neuromuscular blocking drugs, but these discrepancies had never been studied at the orbicularis oculi (OO). The purpose of this study was to verify if the differences in onset time observed at the AP still existed at the OO and to score the intubating conditions using monitoring at the OO after five muscle relaxants. The study included 172 adults aged 18-75 yr. Anesthesia was induced with fentanyl and propofol. Atracurium (0.5 mg/kg), mivacurium (0.20 mg/kg), rocuronium (0.6 mg/kg), succinylcholine (1.0 mg/kg), or vecuronium (0.08 mg/kg) was injected by random allocation. Time to complete disappearance of the response at the OO was assessed visually after train-of-four stimulation of the facial nerve. Laryngoscopy was then performed, and intubating conditions were determined on a scale of 1-4. Results were based on 150 patients. Onset time at the OO was (mean +/- SD): succinylcholine (57 +/- 17 s) < mivacurium (99 +/-19 s) = rocuronium (99 +/- 47 s) < atracurium (129 +/-33 s) = vecuronium (135 +/- 38 s) (P < 0.05). Overall intubating conditions were excellent (84%), good (14%), poor (1.3%), impossible (0.7%), and were similar among the five groups. We conclude that differences in onset time of muscle relaxants observed at the AP were also found at the OO. Visual estimation of the response at the OO correctly predicted good-to-excellent intubating conditions in more than 90% of cases for all the currently available muscle relaxants.\n Onset time of neuromuscular blockade, as estimated visually at the orbicularis oculi, depends on the muscle relaxants given. Regardless of the relaxant used, intubating conditions at loss of orbicularis oculi are acceptable.", "The use of suxamethonium in children is associated with undesirable side effects. The synergistic effect of a rocuronium-mivacurium combination can be considered as an acceptable alternative to suxamethonium in clinical practice. The calculated ED50 of the rocuronium-mivacurium mixture was only 62% of the predicted value assuming a purely additive interaction. The use of this combination has not been evaluated in children. In this two-part study, we assessed the intubating conditions and pharmacodynamics of suxamethonium, rocuronium, mivacurium or a rocuronium-mivacurium combinations in children. We studied 120 ASA I children of both sexes, aged 3-10 yr. Children were premedicated with trimeprazine 2 mg kg-1 orally, and received fentanyl 2 micrograms kg-1 and propofol 2 mg kg-1 for induction of anaesthesia. They were allocated randomly to receive one of the following drugs or drug combinations: suxamethonium 1.0 mg kg-1, mivacurium 0.2 mg kg-1, rocuronium 0.6 or 0.9 mg kg-1, mivacurium 0.1 mg kg-1 with rocuronium 0.3 mg kg-1 or mivacurium 0.15 mg kg-1 with rocuronium 0.45 mg kg-1. In part 1, 60 s after administration of the neuromuscular blocking drug or drug combination, tracheal intubation was performed in 60 children by mimicking rapid sequence induction, and intubating conditions were evaluated by a blinded investigator according to a standard score. In part 2, neuromuscular monitoring was established before administration of neuromuscular blocking agent(s) and the time from injection of drug or drug combination until complete ablation of T1 (onset) and recovery of T1 to 25% (duration) were recorded in another 60 children. The frequency of distribution of excellent or good intubating conditions in the higher dose of rocuronium and the combination groups were similar to those in the suxamethonium group, but significantly different (P < 0.05) from those in the mivacurium group. Mean onset time was faster in the suxamethonium (55.1 (SD 11.4) s), rocuronium 0.9 mg kg-1 (70.5 (37.7) s), mivacurium 0.1 mg kg-1 with rocuronium 0.3 mg kg-1 (67 (35.9) s) and mivacurium 0.15 mg kg-1 with rocuronium 0.45 mg kg-1 (55 (26.7) s) groups compared with the mivacurium 0.2 mg kg-1 (116 (26.8) s) and rocuronium 0.6 mg kg-1 (97.9 (29) s) groups. This study demonstrated that the combination of rocuronium 0.45 mg kg-1 and mivacurium 0.15 mg kg-1 could possibly be considered as an acceptable alternative to suxamethonium when rapid sequence induction of anaesthesia is indicated in children because it provides uniform excellent intubating conditions and complete neuromuscular block in < 60 s.", "We have assessed intubating conditions after administration of Org 9426 (rocuronium) 600 micrograms kg-1 at 60 or 90 s in groups of 20 patients anaesthetized with thiopentone, nitrous oxide in oxygen and small doses of fentanyl, and compared the data with those obtained after suxamethonium 1 mg kg-1 in similar groups of patients. The influence of prior suxamethonium administration on the potency of Org 9426 was studied also by constructing a dose-response curve. Intubating conditions after Org 9426 were found to be clinically acceptable (good or excellent) in 95% of patients at 60 s and in all patients at 90 s and in all patients at both times after suxamethonium. The average time for the onset of block following Org 9426 at this dose was 89 s (which is shorter than with any of the currently available non-depolarizing neuromuscular blocking drugs); the duration of clinical relaxation (25% recovery of twitch height) 30 min. Prior administration of suxamethonium did not appear to influence the potency of Org 9426.", "To compare 4 different anesthesia induction protocols, in a simulated model of rapid-sequence induction, in controlled hypertensive patients.\n Prospective, randomized, double-blind, clinical investigation.\n Large metropolitan university hospital.\n 120 ASA II-III adult hypertensive patients.\n Patients were allocated to 4 groups at random. After preoxygenation for 3 minutes, induction and tracheal intubation was performed in a 30 degrees head-up position. Thiopental (5-7 mg/kg) was the induction agent. Study groups were as follows: group LS (n = 30), lidocaine (1.5 mg/kg) and succinylcholine (1 mg/kg); group LR (n = 30), lidocaine (1.5 mg/kg) and rocuronium (1 mg/kg); group RS (n = 30), remifentanil (1 microg/kg) and succinylcholine (1 mg/kg); group RR (n = 30), remifentanil (1 microg/kg) and rocuronium (1 mg/kg). Patients were intubated 60 seconds after administration of muscle relaxant.\n Hemodynamic data were obtained before induction (baseline), after induction, at intubation, and at 1, 3, 5, and 10 minutes after intubation. More than 20% change in blood pressure and heart rate was considered significant.\n Systolic and mean arterial blood pressures at intubation and 1 and 3 minutes after intubation were higher in group LS compared with groups RS and RR (P < 0.01). Mean arterial blood pressure decreased after induction in groups LS, LR, and RR, but increased at intubation and 1 minute after intubation in groups LS and LR (P < 0.01). Mean arterial blood pressure was similar at all measurement intervals in group RS. The median area under the systolic, mean, and diastolic blood pressure time curves was higher in groups LS and LR compared with groups RS and RR (P < 0.05 and P < 0.01).\n Remifentanil is a better adjunct for attenuation of the response to laryngoscopy and intubation compared with lidocaine, whereas remifentanil-succinylcholine combination appears to be more beneficial in terms of hemodynamic stability in hypertensive patients." ]	Succinylcholine created superior intubation conditions to rocuronium when comparing both excellent and clinically acceptable intubating conditions.
CD003631	[ "1289173" ]	[ "Treatment of pain with pancreatic extracts in chronic pancreatitis: results of a prospective placebo-controlled multicenter trial." ]	[ "According to the theory of negative feedback regulation of pancreatic enzyme secretion by proteases, treatment with pancreatic extracts has been proposed to lower pain in chronic pancreatitis by decreasing pancreatic duct pressure. We conducted a prospective placebo-controlled double blind multicenter study to investigate the effect of porcine pancreatic extracts on pain in chronic pancreatitis. 47 patients with pain (41 males, 6 females) due to chronic pancreatitis documented by sonography, endoscopic retrograde cholangiopancreatography, and CT were included. Exclusion criteria were steatorrhea above 30 g/day, gastric or pancreatic resections in the history, and serum bilirubin above 1.5 mg/dl. Patients received pancreatic extracts (acid-protected microtablets; Panzytrat -20,000; 5 x 2 capsules/day; proteases/capsule 1,000 Pharmacopoea europaea units) for 14 days followed by treatment with placebo for another 14 days or vice versa. Pain (graded from 0 to 3) and concomitant use of analgesics (N-butylscopolaminiumbromide and tramadol) were recorded by diary. Physical examination and blood chemistry were done at day -1, 15 and 29. Quantitative stool fat was determined at days -2/-1, 13/14 and 27/28. 43 patients completed the studies. Pain improved in most patients irrespective of whether they started with placebo or verum. There was no significant difference between both treatment arms. We conclude that pancreatic extracts are not very efficient in lowering pain." ]	Some Chinese medicinal herbs may work in acute pancreatitis. However, because the trials were of low quality, the evidence is too weak to recommend any single herb. Rigorously designed, randomized, double-blind, placebo-controlled trials are required.
CD006873	[ "20393175", "9691103", "16357613", "15362027", "15017504", "7835575", "7876505", "11413109", "10500056", "16339095", "10648454", "19109962", "12801957", "7615189", "16966711", "17241860", "10029609", "9922309", "11113068", "8482443", "1863024" ]	[ "Infliximab, azathioprine, or combination therapy for Crohn's disease.", "A comparison of budesonide and mesalamine for active Crohn's disease. International Budesonide-Mesalamine Study Group.", "Combining infliximab with methotrexate for the induction and maintenance of remission in refractory Crohn's disease: a controlled pilot study.", "Postoperative maintenance of Crohn's disease remission with 6-mercaptopurine, mesalamine, or placebo: a 2-year trial.", "Budesonide versus mesalamine for maintaining remission in patients refusing other immunomodulators for steroid-dependent Crohn's disease.", "Mesalamine in the prevention of endoscopic recurrence after intestinal resection for Crohn's disease. Italian Cooperative Study Group.", "A randomized, double-blind, placebo-controlled trial of the oral mesalamine (5-ASA) preparation, Asacol, in the treatment of symptomatic Crohn's colitis and ileocolitis.", "Interleukin 10 (Tenovil) in the prevention of postoperative recurrence of Crohn's disease.", "Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn's disease.", "Infliximab for induction and maintenance therapy for ulcerative colitis.", "Prophylaxis of postoperative relapse in Crohn's disease with mesalamine: European Cooperative Crohn's Disease Study VI.", "Infliximab prevents Crohn's disease recurrence after ileal resection.", "Infliximab in moderately severe glucocorticoid resistant ulcerative colitis: a randomised controlled trial.", "Prophylactic mesalamine treatment decreases postoperative recurrence of Crohn's disease.", "Adverse events in clinical trials with azathioprine and mesalamine for prevention of postoperative recurrence of Crohn's disease.", "Once-daily, high-concentration MMX mesalamine in active ulcerative colitis.", "Mesalamine in the treatment of mild to moderate active Crohn's ileitis: results of a randomized, multicenter trial.", "Oral budesonide for prevention of postsurgical recurrence in Crohn's disease. The IOIBD Budesonide Study Group.", "Recombinant human interleukin 10 in the treatment of patients with mild to moderately active Crohn's disease. The Interleukin 10 Inflammatory Bowel Disease Cooperative Study Group.", "Mesalamine capsules for the treatment of active Crohn's disease: results of a 16-week trial. Pentasa Crohn's Disease Study Group.", "Oral mesalamine (Asacol) for mildly to moderately active ulcerative colitis. A multicenter study." ]	[ "The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn's disease are unknown.\n In this randomized, double-blind trial, we evaluated the efficacy of infliximab monotherapy, azathioprine monotherapy, and the two drugs combined in 508 adults with moderate-to-severe Crohn's disease who had not undergone previous immunosuppressive or biologic therapy. Patients were randomly assigned to receive an intravenous infusion of 5 mg of infliximab per kilogram of body weight at weeks 0, 2, and 6 and then every 8 weeks plus daily oral placebo capsules; 2.5 mg of oral azathioprine per kilogram daily plus a placebo infusion on the standard schedule; or combination therapy with the two drugs. Patients received study medication through week 30 and could continue in a blinded study extension through week 50.\n Of the 169 patients receiving combination therapy, 96 (56.8%) were in corticosteroid-free clinical remission at week 26 (the primary end point), as compared with 75 of 169 patients (44.4%) receiving infliximab alone (P=0.02) and 51 of 170 patients (30.0%) receiving azathioprine alone (P<0.001 for the comparison with combination therapy and P=0.006 for the comparison with infliximab). Similar numerical trends were found at week 50. At week 26, mucosal healing had occurred in 47 of 107 patients (43.9%) receiving combination therapy, as compared with 28 of 93 patients (30.1%) receiving infliximab (P=0.06) and 18 of 109 patients (16.5%) receiving azathioprine (P<0.001 for the comparison with combination therapy and P=0.02 for the comparison with infliximab). Serious infections developed in 3.9% of patients in the combination-therapy group, 4.9% of those in the infliximab group, and 5.6% of those in the azathioprine group.\n Patients with moderate-to-severe Crohn's disease who were treated with infliximab plus azathioprine or infliximab monotherapy were more likely to have a corticosteroid-free clinical remission than those receiving azathioprine monotherapy. (ClinicalTrials.gov number, NCT00094458.)\n 2010 Massachusetts Medical Society", "Crohn's disease is often treated with glucocorticoids or mesalamine. We compared the efficacy and safety of controlled-ileal-release budesonide capsules and slow-release mesalamine tablets in patients with active Crohn's disease affecting the ileum, the ascending colon, or both.\n In a double-blind, multicenter trial, we enrolled 182 patients with scores of 200 to 400 on the Crohn's Disease Activity Index (with higher scores indicating greater disease activity) and randomly assigned 93 to receive 9 mg of budesonide once daily and 89 to receive 2 g of mesalamine twice daily for 16 weeks. The primary efficacy variable was clinical remission, defined as a score of 150 or less on the Crohn's Disease Activity Index.\n In the analysis of all patients who received at least one dose of study drug, the rates of remission after 8 weeks of treatment were 69 percent in the budesonide group and 45 percent in the mesalamine group (P=0.001); the respective rates after 16 weeks of treatment were 62 percent and 36 percent (P<0.001). Seventy-seven patients in the budesonide group completed the 16 weeks of treatment, as compared with 50 patients in the mesalamine group (P<0.001). The numbers of patients with adverse events were similar in the two groups, but those assigned to budesonide had fewer severe adverse events. Among patients who completed 16 weeks of treatment, the morning plasma cortisol value was normal in 67 percent of budesonide-treated patients and 83 percent of mesalamine-treated patients (P=0.06); 90 percent and 100 percent, respectively, had normal increases in cortisol in response to cosyntropin (P=0.02).\n In patients with active Crohn's disease affecting the ileum, the ascending colon, or both, a controlled-ileal-release formulation of budesonide was more effective in inducing remission than a slow-release formulation of mesalamine.", "Immunosuppression of chronic active Crohn's disease resistant or intolerant to purine antimetabolites still remains a clinical challenge. To obtain long-lasting effects with the anti-TNF-alpha antibody infliximab repeated infusions are often required. Methotrexate has been shown to be a moderately effective drug in maintaining remission in Crohn's disease. The aim of the present pilot study was to evaluate the combination of infliximab and methotrexate as therapy for refractory Crohn's disease.\n Nineteen patients with chronic active Crohn's disease resistant or intolerant to azathioprine were enrolled. Patients received either two infusions of infliximab (5 mg/kg) alone (n=8) or in combination with long-term methotrexate at a dosage of 20 mg/week (n=11) over 48 weeks.\n Two out of eight patients receiving infliximab monotherapy and four out of 11 patients treated with infliximab and concomitant methotrexate had discontinued study treatment by week 48, solely because of lack of efficacy. Clinical remission at week 48 was observed in five out of seven patients treated with infliximab and methotrexate, but only in two out of six patients receiving infliximab monotherapy. In addition, patients treated with concomitant methotrexate achieved remission earlier (median time 2 versus 18 weeks) and needed fewer steroids (median prednisolone dose 0 versus 11.8 mg). Despite an increased mean number of adverse events per patient in the methotrexate group, the proportions of patients experiencing any adverse events and serious adverse events were similar across treatment groups.\n The combination of infliximab with long-term methotrexate may be a promising concept in refractory Crohn's disease. Our data prompt larger trials.", "No therapy has been shown to reliably prevent the evolution of postoperative recurrence of Crohn's disease. The aim of the current trial was to compare 6-mercaptopurine (6-MP) and mesalamine with placebo for the prevention of clinical, endoscopic, and radiographic recurrence of Crohn's disease after resection and ileocolic anastomosis.\n Five centers randomized 131 patients to receive 6-MP (50 mg), mesalamine (3 g), or placebo daily in a double-blind, double-dummy trial. Patients had clinical assessments at 7 weeks and then every 3 months; colonoscopy at 6, 12, and 24 months; and small bowel series at 12 and 24 months. End points were clinical, endoscopic, and radiographic recurrence rates at 24 months.\n Clinical recurrence rates (intent to treat) by life-table analysis at 24 months were 50% (95% confidence interval [CI], 34%-68%), 58% (95% CI, 41%-75%), and 77% (95% CI, 61%-91%) in patients receiving 6-MP, mesalamine, and placebo, respectively. Endoscopic recurrence rates were 43% (95% CI, 28%-63%), 63% (95% CI, 47%-79%), and 64% (95% CI, 46%-81%), and radiographic recurrence rates were 33% (95% CI, 19%-54%), 46% (95% CI, 29%-66%), and 49% (95% CI, 30%-72%), respectively. 6-MP was more effective than placebo ( P < 0.05) at preventing clinical and endoscopic recurrence over 2 years. Patient withdrawals resulted in 69% of the study population evaluable for the clinical recurrence end point.\n 6-MP, 50 mg daily, was more effective than placebo at preventing postoperative recurrence of Crohn's disease and should be considered as a maintenance therapy after ileocolic resection.", "To compare the efficacy of controlled-release budesonide capsules with that of mesalamine for maintaining remission and improving quality of life (QOL) in patients with steroid-dependent Crohn's disease.\n Fifty-seven patients (25 men; mean age, 32 +/- 10.1 yr) with quiescent steroid-dependent Crohn's ileitis, ileocolitis, or colitis (Crohn's disease activity index <150) entered a prospective, investigator-blind trial. Patients were eligible for treatment with azathioprine but had not consented or had developed side effects. Patients were randomized to receive budesonide 6 mg/day (n = 29) or mesalamine 1 g 3 times/day (n = 28). Follow-up assessments were made every 2 months for up to 1 year or until relapse. At each visit, quality of life (QOL) was assessed using the Inflammatory Bowel Disease Questionnaire (IBDQ).\n There were no significant differences in baseline clinical characteristics between the study groups. The 1-year relapse rate was significantly lower in the budesonide group than in the mesalamine group (55% vs. 82%; 95% confidence interval, 12.4%-41%; P = 0.045). Patients assigned to budesonide also remained in remission longer (241 +/- 114 days vs. 147 +/- 117 days; 95% confidence interval, 32.7-155.3 days; P = 0.003). Compared with mesalamine, budesonide treatment also was associated with a better QOL throughout the study (mean total IBDQ scores 165 +/- 36 vs. 182 +/- 28, respectively; 95% confidence interval, -0.4 to 34.4, P = 0.0001). This advantage was confirmed in patients' self-assessed QOL scores.\n Over a 1-year period, controlled-release budesonide was significantly more effective than mesalamine for maintaining remission and improving the QOL of patients with steroid-dependent Crohn's disease.", "Recurrence of lesions of Crohn's disease of the ileum within 1 year after so-called curative resection was well documented by endoscopy in 73%-93% of cases. This study investigated the efficacy of mesalamine in reduction of endoscopic recurrence after surgery.\n In a double-blind, multicenter clinical trial, 87 patients were treated with 3 g/day mesalamine (Pentasa) or with placebo within 1 month after surgery. After 12 months of treatment, severity of endoscopic lesions was recorded with a five-point score; when it was not possible to reach the anastomosis by endoscopy, a barium enema was performed.\n Seventeen clinical relapses (seven in the mesalamine group) were recorded. After 12 months, the endoscopic lesions were less frequent and less severe in the mesalamine group than were those in the placebo group (chi 2, 13.5; P < 0.008). The overall rate of severe recurrence (score of 3-4 on endoscopy or radiological documentation) was 24% in the mesalamine group and 56% in the placebo group (chi 2, 8.57; P < 0.004; difference 32%; 95% confidence interval, 22-52). The odds ratio for active treatment was 4.1.\n This study shows that mesalamine is useful in decreasing the rate and severity of endoscopic recurrences after curative surgery for ileal Crohn's disease.", "Oral mesalamine (Asacol) in a dose of 3.2 g/day was administered in a 16-week placebo-controlled trial in 38 patients for the treatment of mildly to moderately active Crohn's colitis or ileocolitis. Eighteen patients continued a stable dose of prednisone of no more than 20 mg/day and 20 patients did not take prednisone. Changes in the Crohn's Disease Activity Index (CDAI) were used as the primary measure of efficacy. Oral mesalamine was effective in achieving partial or complete remission in 60% of patients as compared with 22% of placebo-treated patients. However, only 20 of 38 patients completed the 17-week study. The others withdrew early because of worsening of symptoms or were dropouts counted as failures. The high percentage of early withdrawals prevented comparison of mean 17-week CDAI scores. Although the number of patients in this study was relatively small, Asacol 3.2 g/day appears to be safe and effective treatment for mildly to moderately active Crohn's colitis and ileocolitis as compared with placebo, and this regimen is an option for treatment of patients who fail or are intolerant of sulfasalazine.", "New lesions of Crohn's disease occur early after ileal or ileocolonic resection and ileocolonic anastomosis. We performed a double blind controlled trial to evaluate the safety and tolerance of recombinant human interleukin 10 (IL-10; Tenovil) in subjects operated on for Crohn's disease. We also assessed the effect of Tenovil in preventing endoscopic recurrence 12 weeks after surgery.\n Patients with Crohn's disease who underwent curative ileal or ileocolonic resection and primary anastomosis were randomised within two weeks after surgery to receive subcutaneous Tenovil 4 microg/kg once daily (QD) (n=22) or 8 microg/kg twice weekly (TIW) (n=21), or placebo (QD or TIW) (n=22). An ileocolonoscopy was performed after 12 weeks of treatment.\n Compliance was excellent. The most frequently observed adverse events were mild and moderate in severity and equally distributed across treatment groups. Thirty seven patients in the pooled Tenovil group and 21 patients in the pooled placebo group were evaluable by endoscopy. At 12 weeks, 11 of 21 patients (52%) in the placebo group had recurrent lesions compared with 17 of 37 patients (46%) in the Tenovil group (ns). The incidence of severe endoscopic recurrence was similar in both groups (9%).\n Tenovil treatment for 12 consecutive weeks in patients with Crohn's disease after intestinal resection was safe and well tolerated. No evidence of prevention of endoscopic recurrence of Crohn's disease by Tenovil was observed.", "Infliximab, an anti-tumor necrosis factor monoclonal antibody, rapidly reduces signs and symptoms of active Crohn's disease. The aim of this study was to determine whether repeated infusions of infliximab would effectively and safely maintain the remitting benefit.\n The efficacy, safety, pharmacokinetics, and immunogenicity of 4 repeated treatments with 10 mg/kg infliximab given every 8 weeks were compared with the effects of placebo in a randomized, double-blind, placebo-controlled, parallel group trial. Seventy-three patients with active Crohn's disease who had not adequately responded to conventional therapies and then had demonstrated a clinical response (>/=70-point decrease in the Crohn's Disease Activity Index) to an initial infusion of infliximab (or placebo) were studied.\n Retreatment with infliximab maintained the clinical benefit through the retreatment period and 8 weeks after the last infusion in nearly all patients retreated with infliximab. Median values for Crohn's Disease Activity Index, inflammatory bowel disease questionnaire (a quality of life measurement), and serum C-reactive protein concentration were maintained at remission levels with infliximab retreatment, but not with placebo retreatment. Retreatment with infliximab every 8 weeks maintained serum infliximab concentration and was well tolerated with a low incidence of immunogenicity. One case of lymphoma and 1 case of suspected lupus were reported; the complete long-term safety profile of infliximab requires additional clinical investigation.\n Long-term treatment with infliximab showed efficacy and tolerability in managing symptoms of patients with active Crohn's disease not responding to conventional treatments.", "Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor alpha, is an established treatment for Crohn's disease but not ulcerative colitis.\n Two randomized, double-blind, placebo-controlled studies--the Active Ulcerative Colitis Trials 1 and 2 (ACT 1 and ACT 2, respectively)--evaluated the efficacy of infliximab for induction and maintenance therapy in adults with ulcerative colitis. In each study, 364 patients with moderate-to-severe active ulcerative colitis despite treatment with concurrent medications received placebo or infliximab (5 mg or 10 mg per kilogram of body weight) intravenously at weeks 0, 2, and 6 and then every eight weeks through week 46 (in ACT 1) or week 22 (in ACT 2). Patients were followed for 54 weeks in ACT 1 and 30 weeks in ACT 2.\n In ACT 1, 69 percent of patients who received 5 mg of infliximab and 61 percent of those who received 10 mg had a clinical response at week 8, as compared with 37 percent of those who received placebo (P<0.001 for both comparisons with placebo). A response was defined as a decrease in the Mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute rectal-bleeding subscore of 0 or 1. In ACT 2, 64 percent of patients who received 5 mg of infliximab and 69 percent of those who received 10 mg had a clinical response at week 8, as compared with 29 percent of those who received placebo (P<0.001 for both comparisons with placebo). In both studies, patients who received infliximab were more likely to have a clinical response at week 30 (P< or =0.002 for all comparisons). In ACT 1, more patients who received 5 mg or 10 mg of infliximab had a clinical response at week 54 (45 percent and 44 percent, respectively) than did those who received placebo (20 percent, P<0.001 for both comparisons).\n Patients with moderate-to-severe active ulcerative colitis treated with infliximab at weeks 0, 2, and 6 and every eight weeks thereafter were more likely to have a clinical response at weeks 8, 30, and 54 than were those receiving placebo. (ClinicalTrials.gov numbers, NCT00036439 and NCT00096655.)\n Copyright 2005 Massachusetts Medical Society.", "This study investigated if long-term treatment with high-dose mesalamine reduces the risk of clinical relapse of Crohn's disease after surgical resection.\n In a prospective, randomized, double-blind, multicenter study, 4 g of mesalamine (Pentasa; Ferring A/S, Vanlose, Denmark) daily was compared with placebo in 318 patients. Treatment was started within 10 days after resective surgery and continued for 18 months. Primary outcome parameter was clinical relapse as defined by an increase in Crohn's Disease Activity Index, reoperation, septic complication, or newly developed fistula. Risk factors for recurrence were prospectively defined to be analyzed in a stepwise proportional hazards model.\n Cumulative relapse rates (+/-SE) after 18 months were 24.5% +/- 3.6% and 31.4% +/- 3.7% in the mesalamine (n = 152) and placebo (n = 166) groups, respectively (P = 0.10, log-rank test, 1-sided). Retrospective analysis showed a significantly reduced relapse rate with mesalamine only in a subgroup of patients with isolated small bowel disease (n = 124; 21.8% +/- 5.6% vs. 39.7% +/- 6.1%; P = 0.02, log-rank test). Probability of relapse was predominantly influenced by the duration of disease (P = 0.0006) and steroid intake before surgery (additional risk, P = 0.0003).\n Eighteen months of mesalamine, 4 g daily, did not significantly affect the postoperative course of Crohn's disease. Some relapse-preventing effect was found in patients with isolated small bowel disease.", "Crohn's disease commonly recurs after intestinal resection. We evaluated whether the administration of infliximab after resective intestinal surgery for Crohn's disease reduces postoperative recurrence.\n We randomly assigned 24 patients with Crohn's disease who had undergone ileocolonic resection to receive intravenous infliximab (5 mg/kg), administered within 4 weeks of surgery and continued for 1 year, or placebo. The primary end point was the proportion of patients with endoscopic recurrence at 1 year. Secondary end points were clinical recurrence and remission and histologic recurrence.\n The rate of endoscopic recurrence at 1 year was significantly lower in the infliximab group (1 of 11 patients; 9.1%) compared with the placebo group (11 of 13 patients; 84.6%) (P = .0006). There was a nonsignificant higher proportion of patients in clinical remission in the infliximab group (8 of 10; 80.0%) compared with the placebo group (7 of 13; 53.8%) (P = .38). The histologic recurrence rate at 1 year was significantly lower in the infliximab group (3 of 11 patients; 27.3%) compared with the placebo group (11 of 13 patients; 84.6%) (P = .01). The occurrence of adverse events was similar between the placebo and infliximab groups, and none occurred in the immediate postoperative period.\n Administration of infliximab after intestinal resective surgery was effective at preventing endoscopic and histologic recurrence of Crohn's disease.", "Tumour necrosis factor production is increased in the mucosa of patients with active ulcerative colitis. The benefits of infliximab in Crohn's disease are established. We investigated its efficacy in ulcerative colitis.\n We conducted a randomised placebo controlled trial of infliximab (5 mg/kg) in the treatment of glucocorticoid resistant ulcerative colitis. Infusions were given at weeks 0 and 2. Disease activity and quality of life were recorded over eight weeks of follow up. Remission was defined as an ulcerative colitis symptom score (UCSS) of < or =2 and/or Baron score of 0 at week 6. Patients not in remission were offered open label infliximab 10 mg/kg and reviewed two weeks later.\n After two weeks, there was no statistically significant difference between the infliximab and placebo groups in the proportion of patients with a Baron score of 0 (13% (3/23) v 5% (1/19) (95% confidence interval (CI) -9% to 24%); p=0.74). After six weeks, remission (UCSS < or =2) rates were 39% (9/23) versus 30% (6/20) (95% CI -19 to 34%; p=0.76). The median improvement in UCSS was 3 for the infliximab group and 2.5 for the placebo group (p=0.82, Mann-Whitney U test). A Baron score of 0 was likely in either group (26% (6/23) v 30% (6/20) (95% CI -30% to 23%); p=0.96). Improvement in the IBDQ and EuroQol was not significantly different between the groups (p=0.22 and 0.3, respectively, Mann-Whitney U test). Twenty eligible patients were given open labelled infusions. Remission was achieved in 3/11 (27%) patients initially treated with infliximab and in 1/9 (11%) patients treated with placebo.\n These data do not support the use of infliximab in the management of moderately active glucocorticoid resistant ulcerative colitis.", "Recurrence of Crohn's disease frequently occurs after surgery. A randomized controlled trial was performed to determine if mesalamine is effective in decreasing the risk of recurrent Crohn's disease after surgical resection is performed.\n One hundred sixty-three patients who underwent a surgical resection and had no evidence of residual disease were randomized to a treatment group (1.5 g mesalamine twice a day) or a placebo control group within 8 weeks of surgery. The follow-up period was a maximum of 72 months.\n The symptomatic recurrence rate (symptoms plus endoscopic and/or radiological confirmation of disease) in the treatment group was 31% (27 of 87) compared with 41% (31 of 76) in the control group (P = 0.031). The relative risk of developing recurrent disease was 0.628 (90% confidence interval, 0.40-0.97) for those in the treatment group (P = 0.039; one-tail test) using an intention-to-treat analysis and 0.532 (90% confidence interval, 0.32-0.87) using an efficacy analysis. The endoscopic and radiological rate of recurrence was also significantly decreased with relative risks of 0.654 (90% confidence interval, 0.47-0.91) in the effectiveness analysis and 0.635 (90% confidence interval, 0.44-0.91) in the efficacy analysis. There was only one serious side effect (pancreatitis) in subjects in the treatment group.\n Mesalamine (3.0 g/day) is effective in decreasing the risk of recurrence of Crohn's disease after surgical resection is performed.", "nan", "SPD476 (LIALDA in the US; MEZAVANT in the EU; otherwise known as MMX mesalamine; Shire Pharmaceuticals Inc., Wayne, PA, under license from Giuliani SpA, Milan, Italy) is a novel, once-daily, high-strength (1.2 g/tablet) formulation of mesalamine, utilizing MMX Multi Matrix System (MMX) technology designed to deliver the active drug throughout the colon. We performed a double-blind, multicenter study, comparing MMX mesalamine vs placebo for the treatment of active ulcerative colitis. A delayed-release oral mesalamine (ASACOL; Procter & Gamble, Cincinnati, OH) reference arm was included.\n Three hundred forty-three patients with active, mild-to-moderate ulcerative colitis received MMX mesalamine 2.4 g/day or 4.8 g/day given once daily, ASACOL 2.4 g/day given in 3 divided doses, or placebo for 8 weeks. The primary end point was the proportion of patients in clinical and endoscopic remission (modified ulcerative colitis disease activity index of < or =1 with rectal bleeding and stool frequency scores of 0, no mucosal friability, and a > or =1-point reduction in sigmoidoscopy score from baseline).\n A significantly greater proportion of patients receiving MMX mesalamine 2.4 g/day given once daily (40.5%; P = .01) and 4.8 g/day given once daily (41.2%; P = .007) achieved clinical and endoscopic remission at week 8, vs placebo (22.1%). The clinical and endoscopic remission rate for ASACOL (32.6%; P = .124) was not significantly superior to placebo. All active treatments were well-tolerated.\n Once-daily MMX mesalamine was efficacious and well-tolerated for the induction of clinical and endoscopic remission. MMX mesalamine offers effective and convenient mesalamine therapy, potentially improving treatment compliance.", "The efficacy of 5-aminosalicylic acid (mesalamine) in the treatment of flare-ups of Crohn's disease is controversial. In previous studies, different locations and pathological behavior of Crohn's disease could have obscured the efficacy of these drugs that deliver their substance in different intestinal sites. The present study tested two different mesalamine formulations with 6-methylprednisolone in mild to moderate active Crohn's ileitis.\n Ninety-four patients with Crohn's ileitis (Crohn's Disease Activity Index [CDAI], 180-350) were randomly assigned to receive for 12 weeks mesalamine tablets, 4 g (35 patients); mesalamine microgranular preparation, 4 g (28 patients); and 6-methylprednisolone, 40 mg (31 patients). Mesalamine microgranular preparation was a gelatin capsule containing 400 mg of mesalamine microgranules coated with Eudragit S, which has been shown to deliver the drug in the terminal ileum.\n Patients taking mesalamine tablets experienced a decrease of CDAI median score value of 113.5 (95% confidence interval [CI], 33-149) compared with 123 (95% CI, 77-155) in the mesalamine microgranular group and 154 (95% CI, 99-197) in the 6-methylprednisolone group (P = 0.07 [NS]). Remission at the final visit occurred in 19 of 31 (61%) patients taking steroids compared with 21 of 35 (60%) patients taking mesalamine tablets and 22 of 28 (79%) patients taking microgranular mesalamine (NS). Five patients on steroids were withdrawn because of side effects, and a case of pancreatitis was related to microgranular mesalamine.\n Mesalamine in microgranular formulation seems to be equally as effective as a standard dosage of steroids in the treatment of the mild to moderate form of Crohn's ileitis.", "Prevention of postoperative recurrence after resection for Crohn's disease (CD) would be of great clinical benefit. The efficacy of oral budesonide for prevention of endoscopic recurrence was evaluated in patients undergoing resection for ileal or ileocecal CD.\n Sixty-three patients received budesonide and 66 received placebo in a double-blind, randomized trial with parallel groups. Ileocolonoscopy, including biopsy, was performed after 3 and 12 months. Indications for surgery were fibrostenosis (78 patients), disease activity (41), and other reasons (10).\n The frequency of endoscopic recurrence did not differ between the groups at 3 and 12 months. In patients with disease activity as indication for surgery, the endoscopic recurrence rate at the anastomosis was lower in the budesonide group at 3 months, although not significantly (21% vs. 47%; P = 0.11), and at 12 months (32% vs. 65%; P = 0.047). There was no such difference with respect to fibrostenosis as indication for surgery. No differences in adverse event patterns were found between the two groups.\n Oral budesonide, 6 mg daily, offered no benefit in prevention of endoscopic recurrence after surgery for ileal/ileocecal fibrostenotic CD but decreased the recurrence rate in patients who had undergone surgery for disease activity.", "Interleukin 10 (IL-10) is an anti-inflammatory, immunomodulatory cytokine that regulates mucosal inflammation. This study evaluated the safety, tolerance, and efficacy of recombinant human IL-10 (rhuIL-10) for mild to moderately active Crohn's disease.\n We conducted a 24-week multicenter, prospective, randomized, double-blind, placebo-controlled, and sequential-escalating-dose study. Ninety-five patients with Crohn's Disease Activity Index of 200-350, not presently undergoing corticosteroid, mesalamine, or immunosuppressive therapy, were treated with subcutaneous rhuIL-10 (1, 5, 10, or 20 microg/kg) or placebo once daily for 28 consecutive days. Patients were followed up for 20 weeks after treatment. Evaluation of safety and tolerance was the first objective, and efficacy was the second objective.\n Adverse effects were dose-related, mild-to-moderate in severity, and reversible. Asymptomatic and reversible anemia and thrombocytopenia were observed at higher doses. No withdrawal or delayed adverse effects were evident during 20 weeks of follow-up. At the end of treatment (day 29), intent-to-treat analysis showed that 23.5% (confidence interval [CI], 6.8%-49.9%) of patients receiving 5 micro/kg rhuIL-10 experienced clinical remission and endoscopic improvement; 0% (CI, 0%-14.8%) of patients in the placebo group did. Higher doses of recombinant human IL-10 were less effective than 5 microg/kg. No rhuIL-10 serum accumulation and no antibody against IL-10 were detected after 4 weeks.\n Subcutaneous rhuIL-10 administered daily for 28 days to patients with mild to moderately active Crohn's disease is safe, well-tolerated, and shows clinical and endoscopic improvement.", "Mesalamine is released from sulfasalazine in the colon and benefits colonic Crohn's disease. The mesalamine used in this study releases the drug throughout the small bowel and colon. Therefore, this study was designed to detect benefit for Crohn's disease involving the small bowel alone or both the colon and small bowel.\n This double-blind, randomized, multicenter prospective controlled trial compared placebo and three daily doses of mesalamine in 310 patients. The primary outcome criterion was change in the Crohn's Disease Activity Index (CDAI) from baseline to final study visit.\n Patients taking 4 g/day mesalamine experienced a decrease of 72 CDAI points compared with 21 points in the placebo group (P < 0.01). Remission occurred in 43% of the 4-g group and 18% of the placebo group. Patients with ileum-only disease showed a 93-point improvement on 4 g mesalamine, compared with a 2-point improvement in similar patients on placebo. Mesalamine in this trial was not associated with clinically significant toxicity.\n This controlled-release mesalamine preparation is safe and effective at 4 g/day as a single agent in treatment of active Crohn's disease of the ileum and colon.", "To evaluate the efficacy and safety of a pH-sensitive, polymer-coated oral preparation of mesalamine in patients with mildly to moderately active ulcerative colitis.\n A multicenter, double-blind, placebo-controlled randomized trial.\n Five university-based medical centers, one inflammatory bowel disease center, and three private practice sites.\n A total of 158 patients with newly or previously diagnosed active ulcerative colitis.\n A pH-sensitive, polymer-coated oral preparation of mesalamine (5-aminosalicylic acid) was used at 1.6 and 2.4 g/d for 6 weeks.\n Efficacy was measured by scores for stool frequency, rectal bleeding, patient's functional assessment, sigmoidoscopic findings, and physician's global assessment. Stringent criteria for disease activity were established prospectively.\n The analysis of protocol-compliant patients showed a significant improvement at 3 weeks in patients taking 2.4 g/d of mesalamine compared with patients taking placebo (32% versus 9%; P = 0.003). At 6 weeks, both the 1.6 g/d (43%) and 2.4 g/d (49%) doses were significantly superior to placebo (23%) (P = 0.03 and P = 0.003, respectively). In addition, more patients worsened in the placebo group compared with the 2.4 g/d group (50% versus 19%; P = 0.003); however, there was no statistically significant difference in worsening between the 1.6 g/d mesalamine group and the placebo group. The oral mesalamine tablet was well tolerated, and no clinically significant changes were observed in hematologic, hepatic, or renal laboratory profiles.\n Colon-targeted oral mesalamine at 2.4 g/d is effective therapy for mildly to moderately active ulcerative colitis. It is well tolerated and should provide a viable therapeutic alternative to sulfasalazine." ]	There are insufficient randomised controlled trials of infliximab, budesonide, tenovil and interleukin-10 to draw conclusions. Nitro-imidazole antibiotics, mesalamine and immunosuppressive therapy with azathioprine/6-MP or infliximab all appear to be superior to placebo for the prevention of post-operative recurrence of Crohn's disease. The cost, toxicity and tolerability of these approaches require careful consideration to determine the optimal approach for post-operative prophylaxis.
CD009774	[ "20020319", "22825926", "20494434", "20145986", "20058059", "15482502", "17700083", "16670650", "17076751", "14622893", "12541005", "12456542", "21418212", "9809262" ]	[ "Randomized controlled trial for early intervention for autism: a pilot study of the Autism 1-2-3 Project.", "A parent-mediated intervention to increase responsive parental behaviors and child communication in children with ASD: a randomized clinical trial.", "Parent-mediated communication-focused treatment in children with autism (PACT): a randomised controlled trial.", "Randomized controlled caregiver mediated joint engagement intervention for toddlers with autism.", "A randomized controlled study of parent-assisted Children's Friendship Training with children having autism spectrum disorders.", "A new social communication intervention for children with autism: pilot randomised controlled treatment study suggesting effectiveness.", "A randomized, controlled trial of a home-based intervention program for children with autism and developmental delay.", "Effects on parental mental health of an education and skills training program for parents of young children with autism: a randomized controlled trial.", "Randomised controlled trial of a parenting intervention in the voluntary sector for reducing child conduct problems: outcomes and mechanisms of change.", "Promoting health and home safety for children of parents with intellectual disability: a randomized controlled trial.", "A pilot randomised control trial of a parent training intervention for pre-school children with autism. Preliminary findings and methodological challenges.", "Improving mental health through parenting programmes: block randomised controlled trial.", "A randomized controlled trial of Hanen's 'More Than Words' in toddlers with early autism symptoms.", "Treatment of children with autism: a randomized controlled trial to evaluate a caregiver-based intervention program in community day-care centers." ]	[ "We piloted a 2-week \"Autism-1-2-3\" early intervention for children with autism and their parents immediately after diagnosis that targeted at (1) eye contact, (2) gesture and (3) vocalization/words. Seventeen children were randomized into the Intervention (n = 9) and Control (n = 8) groups. Outcome measures included the Autism Diagnostic Observation Schedule, Ritvo-Freeman Real Life Rating Scale, Symbolic Play Test, and Parenting Stress Index. Children with autism improved in language/communication, reciprocal social interaction, and symbolic play. Parents perceived significant improvement in their children's language, social interaction, and their own stress level. This intervention can serve as short-term training on communication and social interaction for children with autism, and reduce the stress of their parents during the long waiting time for public health services.", "Longitudinal research has demonstrated that responsive parental behaviors reliably predict subsequent language gains in children with autism spectrum disorder. To investigate the underlying causal mechanisms, we conducted a randomized clinical trial of an experimental intervention (Focused Playtime Intervention, FPI) that aims to enhance responsive parental communication (N = 70). Results showed a significant treatment effect of FPI on responsive parental behaviors. Findings also revealed a conditional effect of FPI on children's expressive language outcomes at 12-month follow up, suggesting that children with baseline language skills below 12 months (n = 24) are most likely to benefit from FPI. Parents of children with more advanced language skills may require intervention strategies that go beyond FPI's focus on responsive communication.", "Results of small trials suggest that early interventions for social communication are effective for the treatment of autism in children. We therefore investigated the efficacy of such an intervention in a larger trial.\n Children with core autism (aged 2 years to 4 years and 11 months) were randomly assigned in a one-to-one ratio to a parent-mediated communication-focused (Preschool Autism Communication Trial [PACT]) intervention or treatment as usual at three specialist centres in the UK. Those assigned to PACT were also given treatment as usual. Randomisation was by use of minimisation of probability in the marginal distribution of treatment centre, age (</=42 months or >42 months), and autism severity (Autism Diagnostic Observation Schedule-Generic [ADOS-G] algorithm score 12-17 or 18-24). Primary outcome was severity of autism symptoms (a total score of social communication algorithm items from ADOS-G, higher score indicating greater severity) at 13 months. Complementary secondary outcomes were measures of parent-child interaction, child language, and adaptive functioning in school. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN58133827.\n 152 children were recruited. 77 were assigned to PACT (London [n=26], Manchester [n=26], and Newcastle [n=25]); and 75 to treatment as usual (London [n=26], Manchester [n=26], and Newcastle [n=23]). At the 13-month endpoint, the severity of symptoms was reduced by 3.9 points (SD 4.7) on the ADOS-G algorithm in the group assigned to PACT, and 2.9 (3.9) in the group assigned to treatment as usual, representing a between-group effect size of -0.24 (95% CI -0.59 to 0.11), after adjustment for centre, sex, socioeconomic status, age, and verbal and non-verbal abilities. Treatment effect was positive for parental synchronous response to child (1.22, 0.85 to 1.59), child initiations with parent (0.41, 0.08 to 0.74), and for parent-child shared attention (0.33, -0.02 to 0.68). Effects on directly assessed language and adaptive functioning in school were small.\n On the basis of our findings, we cannot recommend the addition of the PACT intervention to treatment as usual for the reduction of autism symptoms; however, a clear benefit was noted for parent-child dyadic social communication.\n UK Medical Research Council, and UK Department for Children, Schools and Families.\n Copyright 2010 Elsevier Ltd. All rights reserved.", "This study aimed to determine if a joint attention intervention would result in greater joint engagement between caregivers and toddlers with autism. The intervention consisted of 24 caregiver-mediated sessions with follow-up 1 year later. Compared to caregivers and toddlers randomized to the waitlist control group the immediate treatment (IT) group made significant improvements in targeted areas of joint engagement. The IT group demonstrated significant improvements with medium to large effect sizes in their responsiveness to joint attention and their diversity of functional play acts after the intervention with maintenance of these skills 1 year post-intervention. These are among the first randomized controlled data to suggest that short-term parent-mediated interventions can have important effects on core impairments in toddlers with autism. Clinical Trials #: NCT00065910.", "This study evaluated Children's Friendship Training (CFT), a manualized parent-assisted intervention to improve social skills among second to fifth grade children with autism spectrum disorders. Comparison was made with a delayed treatment control group (DTC). Targeted skills included conversational skills, peer entry skills, developing friendship networks, good sportsmanship, good host behavior during play dates, and handling teasing. At post-testing, the CFT group was superior to the DTC group on parent measures of social skill and play date behavior, and child measures of popularity and loneliness, At 3-month follow-up, parent measures showed significant improvement from baseline. Post-hoc analysis indicated more than 87% of children receiving CFT showed reliable change on at least one measure at post-test and 66.7% after 3 months follow-up.", "Psychosocial treatments are the mainstay of management of autism in the UK but there is a notable lack of a systematic evidence base for their effectiveness. Randomised controlled trial (RCT) studies in this area have been rare but are essential because of the developmental heterogeneity of the disorder. We aimed to test a new theoretically based social communication intervention targeting parental communication in a randomised design against routine care alone.\n The intervention was given in addition to existing care and involved regular monthly therapist contact for 6 months with a further 6 months of 2-monthly consolidation sessions. It aimed to educate parents and train them in adapted communication tailored to their child's individual competencies. Twenty-eight children with autism were randomised between this treatment and routine care alone, stratified for age and baseline severity. Outcome was measured at 12 months from commencement of intervention, using standardised instruments.\n All cases studied met full Autism Diagnostic Interview (ADI) criteria for classical autism. Treatment and controls had similar routine care during the study period and there were no study dropouts after treatment had started. The active treatment group showed significant improvement compared with controls on the primary outcome measure--Autism Diagnostic Observation Schedule (ADOS) total score, particularly in reciprocal social interaction--and on secondary measures of expressive language, communicative initiation and parent-child interaction. Suggestive but non-significant results were found in Vineland Adaptive Behaviour Scales (Communication Sub-domain) and ADOS stereotyped and restricted behaviour domain.\n A Randomised Treatment Trial design of this kind in classical autism is feasible and acceptable to patients. This pilot study suggests significant additional treatment benefits following a targeted (but relatively non-intensive) dyadic social communication treatment, when compared with routine care. The study needs replication on larger and independent samples. It should encourage further RCT designs in this area.", "This study aimed to (1) investigate whether provision of a home-based program in addition to a center-based program improves development in young children with disabilities and coping abilities of their families and (2) describe the characteristics of children and families who benefit most from the intervention.\n Fifty-nine children, aged 3-5 years, with no cerebral palsy, participated in the study. Half of the group was randomized to receive an additional program in their homes. A special education teacher provided 40 visits over 12 months working with the families to help generalize skills to the home environment and assist with their concerns. All children were assessed before and after the intervention, and families completed questionnaires assessing family stress, support, and empowerment on both occasions. Differences in change over time and between the intervention and control group were analyzed by repeated measures and the association between characteristics of children and families with improved outcome by multivariate analysis of variance.\n Change in cognitive development and behavior (in the centers) over time favored the children who received the extra intervention (p = .007 and p = .007, respectively). The groups did not differ on any of the family measures of change. Multivariate analysis of variance revealed more improvement for children in the intervention group from higher than lower stressed families.\n Results suggest the need for daily reinforcement of skills learned at the center-based program and the importance of involving families, especially those with few resources and relatively high stress.", "To determine the impact of a parent education and behavior management intervention (PEBM) on the mental health and adjustment of parents with preschool children with autism.\n A randomized, group-comparison design involving a parent education and counseling intervention to control for nonspecific therapist effects and a control sample was used. Two metropolitan and two rural regions were randomly allocated to intervention groups (n = 70) or control (n = 35). The parents of consecutive children with autism (2(1/2)-5 years old) from the autism assessment services for the intervention regions were then randomly allocated to either a 20-week manual-based parent education and behavior management intervention (n = 35) or a manual-based parent education and counseling intervention (n = 35). The main outcome measure of parental mental health was the General Health Questionnaire used pre- and postintervention and at 6-month follow-up.\n Both treatments resulted in significant and progressive improvement in overall mental health at follow-up (F = 2, 97, p =.007) and mental health significantly improved over time in the 54% of principal caregivers who had the highest levels of mental health problems. The parent education and behavior management intervention was effective in alleviating a greater percentage of anxiety, insomnia, and somatic symptoms and family dysfunction than parent education and counseling at 6-month follow-up.\n A 20-week parent education and skills training program for parents of young children newly diagnosed with autism provides significant improvements in parental mental health and adjustment, justifying its addition to early intervention programs at least for parents with mental health problems.", "To test effectiveness of a parenting intervention, delivered in a community-based voluntary-sector organisation, for reducing conduct problems in clinically-referred children.\n Randomised controlled trial, follow-up at 6, 18 months, assessors blind to treatment status. Participants--76 children referred for conduct problems, aged 2-9, primarily low-income families, randomised to treatment vs. 6-month wait-list group. Retention was 93% at 6 months, 90% at 18 months. Interventions--Webster-Stratton Incredible Years video-based 14-week group programme, teaches cognitive-behavioural principles for managing behaviour, using a collaborative, practical, problem-solving approach. Primary outcomes--child problem behaviour by parent-report (Eyberg) and home-based direct observation; secondary outcomes--observed positive and negative parenting; parent-reported parenting skill, confidence and depression.\n Post-treatment improvements were found in child problem behaviour, by parent-report (effect size (ES) .48, p = .05) and direct observation (ES .78, p = .02); child independent play (ES .77, p = .003); observed negative (ES .74, p = .003) and positive (ES .38, p = .04) parenting; parent-reported confidence (ES .40, p = .03) and skill (ES .65, p =.01), using ANCOVA to control for baseline scores. Maternal depression did not change. Consumer satisfaction was high. At 18-month follow-up, although no randomised comparison was possible, changes appeared to maintain, with no significant change toward baseline level on any measure. Change in observed positive parenting appeared to mediate change in child problem behaviour (p < .025).\n Findings suggest that a group-based cognitive-behavioural parenting programme, delivered by well-trained and supervised staff, can be effective in a community voluntary-sector setting, for reducing conduct problems and enhancing parenting skills. Change in parenting skill appears to be a key mechanism for change in child behaviour. Findings have implications for feasibility of translating evidence-based programmes, even for clinically-referred conduct problems, into less specialised community settings, likely to have lower costs and be more accessible for families.", "The objective of this study was to evaluate the efficacy of a home-based intervention targeted to parents with intellectual disability to promote child health and home safety in the preschool years. A total of 63 parents were recruited for the study with 45 parents (40 mothers and 5 fathers) from 40 families completing the project. The research design permitted comparison between the intervention and three alternative conditions with all parents receiving the intervention in an alternating sequence over the life of the project. The intervention consisted of 10 weekly lessons carried out in the parent's home focusing on child health and home safety. The program was adapted to suit the Australian context from the UCLA Parent--Child Health and Wellness Project (Tymchuk, Groen, & Dolyniuk, 2000). Outcome measures assessed parental health and safety behaviours. Standard measures included parental health, intelligence and literacy. The intervention improved parents' ability to recognize home dangers, to identify precautions to deal with these dangers and resulted in a significant increase in the number of safety precautions parents implemented in their homes with all gains being maintained at 3 months post-intervention. Parents' health behaviours including improved understanding of health and symptoms of illness, knowledge of and skills needed to manage life-threatening emergencies, knowledge about visiting the doctor, knowing when to call, what information to provide and what questions to ask, and how to use medicines safely significantly increased. Again, all gains were maintained 3 months post-intervention. The intervention was effective regardless of parental health, literacy skills, and IQ. This form of home-based intervention promotes a healthy and safe environment which is a prerequisite to continuing parental custody.", "Few attempts have been made to conduct randomised control trials (RCTs) of interventions for pre-school children with autism. We report findings of a pilot RCT for a parent training intervention with a focus on the development of joint attention skills and joint action routines. Twenty-four children meeting ICD-10 criteria for childhood autism (mean age = 23 months) were identified using the CHAT screen and randomised to the parent training group or to local services only. A follow-up was conducted 12 months later (mean age = 35 months). There was some evidence that the parent training group made more progress in language development than the local services group. However, the present pilot study was compromised by several factors: a reliance on parental report to measure language, non-matching of the groups on initial IQ, and a lack of systematic checking regarding the implementation of the parent training intervention. Furthermore, three parents in the local services group commenced intensive, home-based behavioural intervention during the course of the study. The difficulties encountered in the conduct of RCTs for pre-school children with autism are discussed. Methodological challenges and strategies for future well-designed RCTs for autism interventions are highlighted.", "To assess the effectiveness of a parenting programme, delivered by health visitors in primary care, in improving the mental health of children and their parents among a representative general practice population.\n Parents of children aged 2-8 years who scored in the upper 50% on a behaviour inventory were randomised to the Webster-Stratton 10 week parenting programme delivered by trained health visitors, or no intervention. Main outcome measures were the Eyberg Child Behaviour Inventory and the Goodman Strengths and Difficulties Questionnaire to measure child behaviour, and the General Health Questionnaire, Abidin's Parenting Stress Index, and Rosenberg's Self Esteem Scale to measure parents' mental health. These outcomes were measured before and immediately after the intervention, and at six months follow up.\n The intervention was more effective at improving some aspects of the children's mental health, notably conduct problems, than the no intervention control condition. The Goodman conduct problem score was reduced at immediate and six month follow up, and the Eyberg Child Behaviour Inventory was reduced at six months. The intervention also had a short term impact on social dysfunction among parents. These benefits were seen among families with children scoring in the clinical range for behaviour problems and also among children scoring in the non-clinical (normal) range.\n This intervention could make a useful contribution to the prevention of child behaviour problems and to mental health promotion in primary care.", "This randomized controlled trial compared Hanen's 'More than Words' (HMTW), a parent-implemented intervention, to a 'business as usual' control group.\n Sixty-two children (51 boys and 11 girls; M age = 20 months; SD = 2.6) who met criteria for autism spectrum disorders (ASD) and their parents participated in the study. The HMTW intervention was provided over 3.5 months. There were three measurement periods: prior to randomization (Time 1) and at 5 and 9 months post enrollment (Times 2 and 3). Children's communication and parental responsivity were measured at each time point. Children's object interest, a putative moderator, was measured at Time 1.\n There were no main effects of the HMTW intervention on either parental responsivity or children's communication. However, the effects on residualized gains in parental responsivity from Time 1 to both Times 2 and 3 yielded noteworthy effect sizes (Glass's Δ = .71, .50 respectively). In contrast, there were treatment effects on child communication gains to Time 3 that were moderated by children's Time 1 object interest. Children with lower levels of Time 1 object interest exhibited facilitated growth in communication; children with higher levels of object interest exhibited growth attenuation.\n The HMTW intervention showed differential effects on child communication depending on a baseline child factor. HMTW facilitated communication in children with lower levels of Time 1 object interest. Parents of children who evidence higher object interest may require greater support to implement the HMTW strategies, or may require different strategies than those provided by the HMTW curriculum.\n © 2011 The Authors. Journal of Child Psychology and Psychiatry © 2011 Association for Child and Adolescent Mental Health.", "This study reports on the results of a randomized controlled trial that evaluated a caregiver-based intervention program for children with autism in community day-care centers. Thirty-five preschool children with a DSM III-R diagnosis of autism or pervasive developmental disorder were randomized to an experimental or control group. Children in the experimental group were enrolled in day care and their parents and child care workers received a 12-week intervention consisting of lectures and on-site consultations to day-care centers. In addition, supportive work was undertaken with families. Control subjects received day care alone. In the experimental group, there were greater gains in language abilities, significant increases in caregivers' knowledge about autism, greater perception of control on the part of mothers, and greater parent satisfaction. We conclude that this research design demonstrated that the intervention was significantly superior to day care alone." ]	The review finds some evidence for the effectiveness of parent-mediated interventions, most particularly in proximal indicators within parent-child interaction, but also in more distal indicators of child language comprehension and reduction in autism severity. Evidence of whether such interventions may reduce parent stress is inconclusive. The review reinforces the need for attention to be given to early intervention service models that enable parents to contribute skilfully to the treatment of their child with autism. However, practitioners supporting parent-mediated intervention require to monitor levels of parent stress. The ability to draw conclusions from studies would be improved by researchers adopting a common set of outcome measures as the quality of the current evidence is low.
CD000966	[ "12893670", "16585434", "14687871", "17526456" ]	[ "Clozapine v. conventional antipsychotic drugs for treatment-resistant schizophrenia: a re-examination.", "Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment.", "Olanzapine versus clozapine in treatment-resistant or treatment-intolerant schizophrenia.", "Comparison of clozapine-amisulpride and clozapine-quetiapine combinations for patients with schizophrenia who are partially responsive to clozapine: a single-blind randomized study." ]	[ "Although there is a consensus that clozapine is more effective than conventional antipsychotic drugs for treatment-resistant schizophrenia, there is great heterogeneity among results of relevant trials.\n To re-evaluate the evidence comparing clozapine with conventional antipsychotics and to investigate sources of heterogeneity.\n Individual studies were inspected with assessment of clinical relevance of results. Meta-regression analysis was performed to investigate sources of heterogeneity.\n Ten trials were examined. Recent large-scale studies have not found a substantial advantage for clozapine, especially in terms of a clinically relevant effect. Meta-regression showed that shorter study duration, financial support from a drug company and higher baseline symptom score consistently predicted greater advantage of clozapine.\n It may be inappropriate to combine studies in meta-analysis, given the degree of heterogeneity between their findings. The benefits of clozapine compared with conventional treatment may not be substantial.", "When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug, it is unclear what other antipsychotic to switch to and when to use clozapine. In this study, the authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness (CATIE) investigation.\n Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone in phase 1 or 1B of the trials, primarily because of inadequate efficacy, were randomly assigned to open-label treatment with clozapine (N=49) or blinded treatment with another newer atypical antipsychotic not previously received in the trial (olanzapine [N=19], quetiapine [N=15], or risperidone [N=16]).\n Time until treatment discontinuation for any reason was significantly longer for clozapine (median=10.5 months) than for quetiapine (median=3.3), or risperidone (median=2.8), but not for olanzapine (median=2.7). Time to discontinuation because of inadequate therapeutic effect was significantly longer for clozapine than for olanzapine, quetiapine, or risperidone. At 3-month assessments, Positive and Negative Syndrome Scale total scores had decreased more in patients treated with clozapine than in patients treated with quetiapine or risperidone but not olanzapine. One patient treated with clozapine developed agranulocytosis, and another developed eosinophilia; both required treatment discontinuation.\n For these patients with schizophrenia who prospectively failed to improve with an atypical antipsychotic, clozapine was more effective than switching to another newer atypical antipsychotic. Safety monitoring is necessary to detect and manage clozapine's serious side effects.", "Clozapine has been the gold standard for treatment of patients with refractory schizophrenia but is associated with serious safety liabilities. This has prompted the search for therapeutic alternatives for treatment-resistant schizophrenia. The objective of this study was to compare the efficacy and safety of olanzapine versus clozapine in schizophrenic patients who failed to respond adequately to antipsychotic medication or who experienced intolerable adverse effects associated with the medication. This 18-week, randomized, double-blind, parallel study compared treatment with either olanzapine (5-25 mg/day, n=75) or clozapine (100-500 mg/day, n=72) in patients with schizophrenia who were nonresponsive to, or intolerant of, standard acceptable antipsychotic therapy. At the 18-week endpoint, no statistically significant differences were found between olanzapine and clozapine in any efficacy measure used: Positive and Negative Syndrome Scale (PANSS) total, positive, negative, or general psychopathology or Clinical Global Impression severity (CGI-S). Response rates based on the criteria of Kane et al. [Arch. Gen. Psychiatry 45 (1988) 789] were also not significantly different between olanzapine-treated (57.9%) and clozapine-treated patients (60.8%). There were no significant differences in measurements of extrapyramidal symptoms or electrocardiography, and no clinically and statistically significant changes were seen in vital signs or laboratory measures in either group. Both treatments were well tolerated. Olanzapine demonstrated similar efficacy to clozapine in patients who had failed previous treatment because of lack of efficacy (treatment resistance) or intolerable side effects (treatment intolerance). Olanzapine therefore presents a safe alternative in the treatment of refractory schizophrenia.", "Schizophrenia is a devastating psychiatric disorder. Clozapine has long been the gold standard for treatment of patients with treatment-resistant schizophrenia; however, some patients are only partially responsive to clozapine treatment. Augmentation of clozapine treatment might enhance its effectiveness in partial responders, but only a few studies have investigated possible augmentation strategies. This study compared the effectiveness and tolerability of the combination of amisulpride and clozapine with the combination of quetiapine and clozapine in patients who were only partially responsive to clozapine monotherapy. Fifty-six treatment-resistant patients who were partially responsive to clozapine were randomly assigned to receive amisulpride or quetiapine along with an ongoing stable dose of clozapine. Fifty patients completed the study. Patients were evaluated at baseline and at the first, third, sixth, and eighth weeks. Efficacy measures consisted of the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the Scale for the Assessment of Positive Symptoms (SAPS), and the Clinical Global Impression (CGI) scale. Tolerability and adverse effects were assessed with the Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale and the Simpson Angus Scale (SAS). A substantial improvement occurred in both groups by the end of the eighth week; however, the improvement associated with amisulpride was significantly greater than that seen with quetiapine. This difference was noted as early as the third week of follow-up in terms of CGI scores, and by the sixth week with regard to BPRS, SANS, and SAPS scores. Both drugs were well tolerated, as measured by UKU and SAS. Improvement favoring clozapine+amisulpride could be attributed to the selective D2/D3 binding property of amisulpride, which had an additional effect in improving symptoms of schizophrenia. The authors concluded that amisulpride seems to be effective and well tolerated for augmentation purposes in clozapine-resistant patients." ]	The equal effectiveness and tolerability of new atypical drugs in comparison with clozapine is not yet demonstrated. Lack of statistical power to determine the comparative efficacy and effectiveness of newer atypical drugs makes it difficult to judge whether newer drugs are more effective, less effective or equivalent. Trials of sufficient power, with longer duration, measuring clinically important outcomes, are needed to assess the true comparative clinical effectiveness, tolerability and cost effectiveness of newer drugs in relation to clozapine.
CD000979	[ "10445363", "7709907", "2617141", "16202046", "2133940", "2086265", "9082855", "6943157" ]	[ "Long-term follow-up of early treatment of unilateral forced posterior cross-bite. Orofacial status.", "A clinical investigation of the correction of unilateral first molar crossbite with a transpalatal arch.", "Longitudinal study on the effect of early interceptive treatment in 4-year-old children with unilateral cross-bite.", "An evaluation of the effects of two distal extension removable partial denture designs on tooth stabilization and periodontal health.", "Two-point rapid palatal expansion: an alternate approach to traditional treatment.", "Anterior open bite treatment with magnets.", "Skeletal and dental changes after maxillary expansion in the mixed dentition.", "Effect of stannous fluoride treatments on the progression of initial lesions in approximal surfaces of permanent posterior teeth." ]	[ "Twenty-nine subjects, 20 years old on average and all treated at 4 years of age for unilateral forced posterior dento-alveolar cross-bite by grinding or by expansion of the upper dental arch, were clinically examined to evaluate the long-term effects of their treatment. The frequency of successful treatment-indicated as stable correction of the cross-bite-by means of only 1 treatment sequence was 59%; by grinding, 57%; and by expansion, 60%. The 18 subjects that had only been treated at the age of 4 years formed the 'early group' in our study. Eleven of our subjects had been retreated later in the mixed or permanent dentition because of a relapse of the unilateral forced posterior cross-bite and formed the 'late group'. A significantly higher frequency of mouth breathing, breathing obstacles, and snoring was found in this group. According to our clinical investigation, 2 of the subjects in our cohort still had a unilateral forced posterior cross-bite. Our findings regarding masticatory performance, bite force, and endurance showed no significant differences between the initial cross-bite and the healthy sides or between the early and the late group subjects, which showed that the masticatory function of the treated subjects was symmetrical. Grinding and expansion treatments seem to display similar success rates in the long-term regarding correction of unilateral posterior forced cross-bite.", "The correction of a unilateral first molar crossbite with a Goshgarian type of transpalatal arch was evaluated in 35 children from 6 years, 8 months to 15 years, 11 months old. Fifteen of the children were treated with an arch activated for expansion only and 20 children with an arch activated in a similar way but with the inclusion of buccal root torque of the anchorage tooth. With both types of activation, the arches worked in a statically determinate system, i.e., the tooth in crossbite was allowed to tip buccally. The movements of the first molars as a result of the treatment were monitored by measurements on dental casts and frontal cephalometric roentgenograms. In addition, the width of the midpalatal suture was measured on occlusal roentgenograms of the maxilla. In the children treated with an arch activated only for expansion, the molars on both sides of the dental arch moved buccally during the treatment. In the children treated by torque activation, on the other hand, there was a considerable buccal movement of the molar on the side of the crossbite without any significant buccal movement of the anchorage tooth. In individual cases, the molar on the noncrossbite side moved and tipped palatally and in some cases buccally but to a minor degree. With both types of activation, there was only a slight change in inclination of the transverse occlusal plane through the first molars; the plane opened up slightly toward the side of the crossbite. For both types of activation, there was a slight widening of the palatal suture during the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)", "To evaluate the results of early interceptive grinding and also the possibility of self-correction of unilateral cross-bite, 76 4-yr-old children with this malocclusion were divided into one treated and one untreated group. In the treatment group 50% of the children exhibited a normal transverse occlusion evaluated in the mixed dentition, at the age of 9. In the untreated group only 17% showed a spontaneous correction of the cross-bite. Among the studied dental variables the \"max./mand. arch width difference\" especially in the canine region was found to be a valuable predictor indicating whether cross-bite can be successfully treated in preschoolchildren by selective grinding. The results of this study support early treatment of unilateral cross-bite and gives the criteria whereby successful treatment by selective grinding may be expected.", "A 30-month follow-up study was conducted on 36 patients to evaluate the effects of the lingual plate as a major connector in distally extended removable partial dentures (RPDs) on tooth stabilization. At the same time, the study evaluated the effects of lingual plate-type RPDs and lingual bar-type RPDs on periodontal health. The most striking finding of the study was that, with the exception of gingival recession (GR), periodontal conditions improved with both types of RPDs. At the end of 30 months, there were significant differences in plaque index, GR and tooth mobility (TM) values between treatment groups (P < 0.05). Plaque accumulation was greater in the lingual plate treatment group; however, this did not result in periodontal breakdown. There were no statistically significant differences between treatment groups with respect to pocket depth, gingival index or attachment loss (P > 0.05). Moreover, patients treated with lingual plate-type RPDs demonstrated less TM when compared with patients treated with lingual bar-type RPDs at the end of 30 months follow-up. Overall study findings established that with adequate checks on oral and denture hygiene at regular intervals, patients with RPDs may even experience improved periodontal health. Moreover, the clinical interpretation of decreased TM observed in patients treated with lingual plate-type RPDs may be questionable as the plaque accumulation was greater in the lingual plate treatment group inspite of periodic recalls.", "Rapid palatal expansion (RPE) causes separation of the lateral halves of the palate and traditionally has used four maxillary teeth as anchorage. The purpose of this study was to introduce a rapid palatal expander that requires only two anchor teeth (two-point RPEe) and to compare the expansion obtained with that from a Hyrax appliance. This study involved two groups of 25 children aged 7 to 15 years who were treated in a private orthodontist's office with either a Hyrax appliance or a two-point RPEe. Dental casts and occlusal radiographs were made before treatment and at least three months after stabilization of the appliance. Paired t-tests were performed to identify significant intragroup changes, and independent t-tests were performed to determine intergroup differences. The findings showed the two-point RPEe was as efficient as the Hyrax in obtaining dental expansion of the maxillary posterior teeth with less effect on the maxillary anterior and mandibular teeth. Therefore, the two-point RPEe may be useful in certain clinical situations.", "The aim of this study was to examine the effects of repelling magnets on the treatment of anterior open bite and compare them with the effects of acrylic posterior bite-blocks. Twenty patients, aged 9-16 years with skeletal anterior open bite, were randomly divided into two groups. In one group the patients wore posterior repelling magnet splints and in the other they wore acrylic posterior bite-blocks of the same thickness as the magnet splints. The patients were instructed to use their appliance as much as possible (the minimum accepted being 18 hours daily) during a 6-month period. Dental casts, intra-oral photos, and lateral cephalograms were taken before and after treatment, and the patients were also examined regularly to identify the development of any craniomandibular disorders. In the first group, the dental and skeletal vertical relation responded quickly to the magnet treatment. The open bite was generally closed in just under 4 months, especially in patients in early mixed dentition. Spacing in the labial segments decreased in some cases, while slight crowding was induced in others. Transverse problems, i.e. unilateral cross-bite, sometimes followed by scissor-bite on the opposite side, was observed in those patients who were in the early mixed dentition and had used the magnets intensively. The patients who wore acrylic posterior bite-blocks also showed improvement in the dental and skeletal vertical relationships, especially during the first months. This was followed by a 'plateau' period. No transverse problems were found in these patients.", "The purpose of this study was to compare skeletal and dental aspects of three different expansion methods in the mixed dentition period in sagittal, vertical, and transversal planes, treatment periods, complications, and relapse tendencies in early periods. Patients with unilateral or bilateral posterior crossbites in the mixed dentition were studied. They were divided into three groups of 10 patients in each group. The first group received treatment with removable plates for semirapid maxillary expansion; the second group with quad-helix appliances for slow maxillary expansion; and the third group with conventional fixed hyrax appliances for rapid maxillary expansion (RME). Lateral and posteroanterior cephalometric films, occlusal films, and dental casts were taken before and after expansion, and after retention with the same appliances. Cephalometric and dental cast analyses were made. Both skeletal and dental changes were observed after all three expansion methods.", "Bite-wing radiographs were used to determine the effect of three forms of topical SnF2 therapy on the progression of initial lesions in the approximal surfaces of permanent posterior teeth. Radiographs were taken annually over a four-year period. The subjects were schoolchildren, aged 12-14 yr, living in a low fluoride area. The professional application of a 10% SnF2 solution for 30 s, semi-annually for two yr, had no discernible effect on the development of the initial lesions. However, the home use of a SnF2 dentifrice did inhibit caries progression appreciably at all but one of the four time intervals in the study. The professional application of a 10% SnF2 solution for 30 s, semi-annually for two yr, combined with the home use of a SnF2 dentifrice, was the most effective treatment in retarding lesion development. Even without topical fluoride therapy, the rate of progression of initial approximal lesions was generally quite slow. In view of these findings, it would seem sound clinical practice to treat all initial lesions in approximal surfaces with topical fluoride therapy and delay placement of restorations until there is radiographic evidence of lesions reaching dentin." ]	The evidence from the trials reported by Thilander 1984 and Lindner 1989 suggests that removal of premature contacts of the baby teeth is effective in preventing a posterior crossbite from being perpetuated to the mixed dentition and adult teeth. When grinding alone is not effective, using an upper removable expansion plate to expand the top teeth will decrease the risk of a posterior crossbite from being perpetuated to the permanent dentition.The comparisons of treatments made in the trials reported by Mossaz-Joëlson 1989; Schneidman 1990; Ingervall 1995; Asanza 1997 and Sandikçioglu 1997 were inconclusive so recommendations for clinical practice can not be made based on the results of these trials. However, these trials were small and inadequately powered so further studies, with appropriate sample sizes, would be required to assess the relative effectiveness of these interventions.
CD002029	[ "9492666", "9885092", "9373419", "9300508", "11086269", "8297057", "15939927", "3828594", "11037083", "18667099", "3746764", "10665619", "16551144", "19967577", "15596155", "15588746" ]	[ "Evaluation of adjuvant psychological therapy in patients with testicular cancer: randomised controlled trial.", "A randomized controlled trial of the effects of group psychological therapy on survival in women with metastatic breast cancer.", "London-East Anglia randomised controlled trial of cognitive-behavioural therapy for psychosis. I: effects of the treatment phase.", "A controlled trial of cognitive behavioural therapy for non-cardiac chest pain.", "Randomised controlled trial of non-directive counselling, cognitive-behaviour therapy and usual general practitioner care in the management of depression as well as mixed anxiety and depression in primary care.", "The efficacy of psychological, educational, and behavioral treatment. Confirmation from meta-analysis.", "Effect of individual psychological intervention in Chinese women with gynecologic malignancy: a randomized controlled trial.", "A controlled trial of treatments for generalized anxiety.", "Randomized controlled trial of cognitive behaviour therapy for repeated consultations for medically unexplained complaints: a feasibility study in Sri Lanka.", "Cognitive behaviour therapy for violent men with antisocial personality disorder in the community: an exploratory randomized controlled trial.", "Psychological treatment in general practice: its effect on patients and their families.", "A randomized controlled trial of cognitive-behavioral therapy for persistent symptoms in schizophrenia resistant to medication.", "Evaluation of universal, indicated, and combined cognitive-behavioral approaches to the prevention of depression among adolescents.", "Motivational interviewing versus cognitive behavioral group therapy in the treatment of problem and pathological gambling: a randomized controlled trial.", "Psychosocial interventions for somatizing patients by the general practitioner: a randomized controlled trial.", "An analysis of the effect of funding source in randomized clinical trials of second generation antipsychotics for the treatment of schizophrenia." ]	[ "To determine the efficacy of adjuvant psychological therapy in patients with testicular cancer and to compare the characteristics and psychosocial outcomes of men who agreed to participate with those who declined to participate in a randomised trial of psychological intervention.\n Newly diagnosed patients were asked to participate in a randomised trial of psychological support compared with standard medical care. Participants and non-participants completed self assessment questionnaires at baseline and at 2, 4 and 12 months.\n Testicular Tumour Unit of the Royal Marsden Hospital.\n 73 of 184 (40%) eligible patients agreed to enter the randomised trial (participants) and 81 (44%) declined to participate but agreed to complete further assessments (non-participants). 30 patients wanted no further contact with the researchers.\n Hospital anxiety and depression scale, psychosocial adjustment to illness scale, Rotterdam symptom checklist, mental adjustment to cancer scale. Only scores on the hospital anxiety and depression scale are reported for evaluating treatment efficacy.\n 111 of 184 (60%) eligible men declined to participate in the trial. Patients with stage I disease were most likely to refuse to participate. A patient was less likely to participate if he had low volume disease and was receiving no further treatment. Likelihood of participation was associated with stage of disease and with type of primary treatment (P < 0.001 for heterogeneity). Patients with early stage disease (P < 0.001) and fewer physical symptoms (P < 0.001) were less likely to participate. Psychosocial factors associated with participation included anxious preoccupation regarding disease (P = 0.01). There were no differences in outcome between participants and non-participants during follow up. Patients seemed to gain little benefit from adjuvant psychological therapy. At 2 months change from baseline favoured the treated group in the anxiety subscale (mean difference between groups -1.41 (95% confidence interval -2.86 to 0.03)). This was not sustained when adjusted for factors related to the disease. By 12 months change from baseline seemed to favour the control group (mean difference between groups 1.66 (-0.18 to 3.50)).\n Patients with testicular cancer seem to have considerable coping abilities. Those who declined to participate in the trial differed from those who participated. Those who agreed to participate may comprise the clinical group who perceive a need for psychological support. No evidence was found to indicate a need for routinely offering adjuvant psychological therapy.", "In order to test the effect of a psychological intervention on survival from cancer, 66 women with metastatic breast cancer, all receiving standard medical care, were randomly assigned into two groups; one group (n = 30) attended the psychological intervention, consisting of 35 weekly, 2 h sessions of supportive plus cognitive behavioral therapy; the control group (n = 36) received only a home study cognitive behavioral package. No significant difference was found in survival post-randomization between the groups as assessed by a log rank test 5 years after the commencement of the study. As expected, several prognostic factors were significant predictors of survival: metastatic site, hormonal receptor status, and chemotherapy prior to randomization. While many personal and demographic variables did not influence survival, there was a significant effect of self-reported exercise (possibly due to better health). A small subgroup of intervention subjects who attended outside support groups also survived significantly longer than those who did not. The strengths and limitations of the present study are discussed, and the results contrasted with those of a well known study by Spiegel et al. (Spiegel, D., Bloom, J.R., Kraemer, H.C. and Gottheil, E. (1989) Lancet ii, 888-891). We propose that a different experimental design (correlative) may be needed to show any effect of self-help behaviors and psychological attributes in a small minority of patients.", "A series of small, mainly uncontrolled, studies have suggested that techniques adapted from cognitive-behavioural therapy (CBT) for depression can improve outcome in psychosis, but no large randomised controlled trial of intensive treatment for medication-resistant symptoms of psychosis has previously been published.\n Sixty participants who each had at least one positive and distressing symptom of psychosis that was medication-resistant were randomly allocated between a CBT and standard care condition (n = 28) and a standard care only control condition (n = 32). Therapy was individualised, and lasted for nine months. Multiple assessments of outcome were used.\n Over nine months, improvement was significant only in the treatment group, who showed a 25% reduction on the BPRS. No other clinical, symptomatic or functioning measure changed significantly. Participants had a low drop-out rate from therapy (11%), and expressed high levels of satisfaction with treatment (80%). Fifty per cent of the CBT group were treatment responders (one person became worse), compared with 31% of the control group (three people became worse and another committed suicide).\n CBT for psychosis can improve overall symptomatology. The findings provide evidence that even a refractory group of clients with a long history of psychosis can engage in talking about psychotic symptoms and their meaning, and this can improve outcome.", "The majority of patients presenting to cardiac clinics with chest pain who are reassured they do not have heart disease or other serious physical disorder continue to experience symptoms, worry about heart disease and restrict their activities. This randomized trial investigated the effectiveness of psychological treatment within routine cardiac care.\n Consecutive patients presenting with chest pain and reassured by a cardiologist they do not have heart disease were reassessed 6 weeks later. Those with persistent limiting symptoms were offered the opportunity to participate in a trial of cognitive behavioural therapy.\n Thirty-seven subjects agreed to take part. A number of subjects were unenthusiastic about psychological intervention or, following explanation of the study, regarded further treatment as not being necessary. At 3 months there were significant differences between the treatment group and the control group on key outcome measures of symptoms, mood and activity. At 6 months there were fewer differences but significant advantages of treatment in terms of limitation of activities and worry about physical symptoms.\n We conclude that there is a need for 'stepped' further care following reassurance in the cardiac clinic and that cognitive behavioural treatment is effective with those with persistent disabling symptoms.", "The aim of this study was to determine both the clinical and cost-effectiveness of usual general practitioner (GP) care compared with two types of brief psychological therapy (non-directive counselling and cognitive-behaviour therapy) in the management of depression as well as mixed anxiety and depression in the primary care setting.\n The design was principally a pragmatic randomised controlled trial, but was accompanied by two additional allocation methods allowing patient preference: the option of a specific choice of treatment (preference allocation) and the option to be randomised between the psychological therapies only. Of the 464 patients allocated to the three treatments, 197 were randomised between the three treatments, 137 chose a specific treatment, and 130 were randomised between the psychological therapies only. The patients underwent follow-up assessments at 4 and 12 months.\n The study was conducted in 24 general practices in Greater Manchester and London.\n A total of 464 eligible patients, aged 18 years and over, were referred by 73 GPs and allocated to one of the psychological therapies or usual GP care for depressive symptoms.\n The interventions consisted of brief psychological therapy (12 sessions maximum) or usual GP care. Non-directive counselling was provided by counsellors who were qualified for accreditation by the British Association for Counselling. Cognitive-behaviour therapy was provided by clinical psychologists who were qualified for accreditation by the British Association for Behavioural and Cognitive Psychotherapies. Usual GP care included discussions with patients and the prescription of medication, but GPs were asked to refrain from referring patients for psychological intervention for at least 4 months. Most therapy sessions took place on a weekly basis in the general practices. By the 12-month follow-up, GP care in some cases did include referral to mental healthcare specialists.\n The clinical outcomes included depressive symptoms, general psychiatric symptoms, social function and patient satisfaction. The economic outcomes included direct and indirect costs and quality of life. Assessments were carried out at baseline during face-to-face interviews as well as at 4 and 12 months in person or by post.\n At 4 months, both psychological therapies had reduced depressive symptoms to a significantly greater extent than usual GP care. Patients in the psychological therapy groups exhibited mean scores on the Beck Depression Inventory that were 4-5 points lower than the mean score of patients in the usual GP care group, a difference that was also clinically significant. These differences did not generalize to other measures of outcome. There was no significant difference in outcome between the two psychological therapies when they were compared directly using all 260 patients randomised to a psychological therapy by either randomised allocation method. At 12 months, the patients in all three groups had improved to the same extent. The lack of a significant difference between the treatment groups at this point resulted from greater improvement of the patients in the GP care group between the 4- and 12-month follow-ups. At 4 months, patients in both psychological therapy groups were more satisfied with their treatment than those in the usual GP care group. However, by 12 months, patients who had received non-directive counselling were more satisfied than those in either of the other two groups. There were few differences in the baseline characteristics of patients who were randomised or expressed a treatment preference, and no differences in outcome between these patients. Similar outcomes were found for patients who chose either psychological therapy. Again, there were no significant differences between the two groups at 4 or 12 months. Patients who chose counselling were more satisfied with treatment than those who chose c", "Conventional reviews of research on the efficacy of psychological, educational, and behavioral treatments often find considerable variation in outcome among studies and, as a consequence, fail to reach firm conclusions about the overall effectiveness of the interventions in question. In contrast meta-analytic reviews show a strong, dramatic pattern of positive overall effects that cannot readily be explained as artifacts of meta-analytic technique or generalized placebo effects. Moreover, the effects are not so small that they can be dismissed as lacking practical or clinical significance. Although meta-analysis has limitations, there are good reasons to believe that its results are more credible than those of conventional reviews and to conclude that well-developed psychological, educational, and behavioral treatment is generally efficacious.", "To evaluate the effectiveness of psychological intervention in the care of cancer patients and to determine whether routine use of individual psychological therapies is indicated.\n Patients with newly diagnosed gynecologic malignancies from August 1999 to November 2000 were recruited and randomly assigned to either a control group receiving routine medical care or to an intervention group receiving individual psychotherapy. A set of fixed-choice, self-report questionnaires assessing the patients' psychological status, quality of life, and their perceptions related to the medical consultations was completed at recruitment and then every 3 months for 18 months. Data analysis was performed according to the intention-to-treat principle by fitting the data into a linear mixed-effects model. Multivariable analyses were performed to examine the effects of confounding factors.\n One hundred fifty-five patients participated in the trial. There were no statistically significant differences between the two groups at baseline. There was a trend toward better quality of life and functional status and also improvement of the symptoms over time for both groups. No differences were found between the groups in the scores measured by any of the instruments at baseline and at any time points after the cancer diagnosis. Psychological intervention had no significant effects on the psychosocial parameters.\n Routine use of psychological therapies as given in our format has no significant effect on the patients' quality of life and psychological status.", "Treatments for chronic anxiety have received considerable interest recently. Firstly, there is a body of research which has shown problems of dependence and habituation in the long-term use of anti-anxiety drugs. A second development is that of psychological treatments for anxiety. Because of the problems involved in the use of benzodiazepines, it is important to determine whether or not psychological treatments are a reasonable alternative when treating chronic anxiety. This study was designed to test the relative effectiveness of cognitive-behavioural therapy, anxiety management training and treatment by benzodiazepines against a waiting list control. Measures were taken on both the process and outcome of treatment. The most immediate and greatest improvements in anxiety were seen in the group receiving drugs. However, these improvements reduced as the trial progressed and were minimal at the end of therapy. Both psychological treatment groups improved as the trial progressed with the most significant and consistent changes seen in the cognitive-behaviour therapy group. However, at follow-up there was no difference between the two groups receiving psychological treatments. Because of their lack of sustained improvement, over half of the group receiving drugs refused to wait without treatment until the follow-up assessment.", "Research on the management and the outcome of treatment of medically unexplained symptoms is very limited. Development of simple but effective techniques for treatment and demonstration of their effectiveness when applied in primary health care are needed.\n A randomized controlled trial was carried out with follow-up assessments at 3 months after baseline assessments using the Short Explanatory Model Interview (SEMI), General Health Questionnaire (GHQ-30), Bradford Somatic Inventory (BSI) and patient satisfaction on a visual analogue scale. The study was carried out in a general out-patient clinic in Sri Lanka. The intervention group received six, 30 min sessions based on the principles of cognitive behavioural therapy over a period of 3 months. The control group received standard clinical care.\n Eighty patients out of the 110 patients referred, were eligible. Sixty-eight were randomly allocated equally to the control and treatment groups. All 34 in the treatment group accepted the treatment offer and 22 completed between three and six sessions. At 3 months, 24 in the treatment and 21 in the control group completed follow-up assessments. Intention-to-treat analysis revealed significant differences in mean scores of outcome measures (adjusted for baseline scores) between control and intervention groups respectively--complaints 6.1 and 3.8 (P = 0.001), GHQ 10.4 and 6.3 (P = 0.04), BSI score 15.6 and 132 (P < 0-01), visits 7.9 and 3.1 (P = 0.004).\n Intervention based on cognitive behavioural therapy is feasible and acceptable to patients with medically unexplained symptoms from a general out-patients clinic in Sri Lanka. It had a significant effective in reducing symptoms, visits and distress, and in increasing patient satisfaction.", "Little information exists on treatment effectiveness in antisocial personality disorder (ASPD). We investigated the feasibility and effectiveness of carrying out a randomized controlled trial of cognitive behaviour therapy (CBT) in men with ASPD who were aggressive.\n This was an exploratory two-centre, randomized controlled trial in a community setting. Fifty-two adult men with a diagnosis of ASPD, with acts of aggression in the 6 months prior to the study, were randomized to either treatment as usual (TAU) plus CBT, or usual treatment alone. Change over 12 months of follow-up was assessed in the occurrence of any act of aggression and also in terms of alcohol misuse, mental state, beliefs and social functioning.\n The follow-up rate was 79%. At 12 months, both groups reported a decrease in the occurrence of any acts of verbal or physical aggression. Trends in the data, in favour of CBT, were noted for problematic drinking, social functioning and beliefs about others.\n CBT did not improve outcomes more than usual treatment for men with ASPD who are aggressive and living in the community in this exploratory study. However, the data suggest that a larger study is required to fully assess the effectiveness of CBT in reducing aggression, alcohol misuse and improving social functioning and view of others. It is feasible to carry out a rigorous randomized controlled trial in this group.", "Rates of consultations and prescriptions for patients referred to clinical psychologists, and for these patients' immediate families, were investigated for three-year periods both before and after referral. Patients and their children consulted more and had more medication prescribed before referral than control groups, this tendency being particularly prevalent in the year before referral. After the contact with the psychologist there was a decrease in all these indices in the short term, and there were long-term decreases in psychotropic drug prescriptions for patients and in both consultations and prescriptions for their children.", "Research evidence supports the efficacy of cognitive-behavioral therapy in the treatment of drug-refractory positive symptoms of schizophrenia. Although the cumulative evidence is strong, early controlled trials showed methodological limitations.\n A randomized controlled design was used to compare the efficacy of manualized cognitive-behavioral therapy developed particularly for schizophrenia with that of a nonspecific befriending control intervention. Both interventions were delivered by 2 experienced nurses who received regular supervision. Patients were assessed by blind raters at baseline, after treatment (lasting up to 9 months), and at a 9-month follow-up evaluation. Patients continued to receive routine care throughout the study. An assessor blind to the patients' treatment groups rated the technical quality of audiotaped sessions chosen at random. Analysis was by intention to treat.\n Ninety patients received a mean of 19 individual treatment sessions over 9 months, with no significant between-group differences in treatment duration. Both interventions resulted in significant reductions in positive and negative symptoms and depression. At the 9-month follow-up evaluation, patients who had received cognitive therapy continued to improve, while those in the befriending group did not. These results were not attributable to changes in prescribed medication.\n Cognitive-behavioral therapy is effective in treating negative as well as positive symptoms in schizophrenia resistant to standard antipsychotic drugs, with its efficacy sustained over 9 months of follow-up.", "A cluster, stratified randomized design was used to evaluate the impact of universal, indicated, and combined universal plus indicated cognitive- behavioral approaches to the prevention of depression among 13- to 15-year-olds initially reporting elevated symptoms of depression. None of the intervention approaches differed significantly from a no-intervention condition or from each other on changes in depressive symptoms, anxiety, externalizing problems, coping skills, and social adjustment. All high-symptom students, irrespective of condition, showed a significant decline in depressive symptoms and improvement in emotional well-being over time although they still demonstrated elevated levels of psychopathology compared with the general population of peers at 12-month follow-up. There were also no significant intervention effects for the universal intervention in comparison with no intervention for the total sample of students in those conditions.\n Copyright (c) 2006 APA, all rights reserved.", "Pathological gambling is a widespread problem with major implications for society and the individual. There are effective treatments, but little is known about the relative effectiveness of different treatments. The aim of this study was to test the effectiveness of motivational interviewing, cognitive behavioral group therapy, and a no-treatment control (wait-list) in the treatment of pathological gambling. This was done in a randomized controlled trial at an outpatient dependency clinic at Karolinska Institute (Stockholm, Sweden). A total of 150 primarily self-recruited patients with current gambling problems or pathological gambling according to an NORC DSM-IV screen for gambling problems were randomized to four individual sessions of motivational interviewing (MI), eight sessions of cognitive behavioral group therapy (CBGT), or a no-treatment wait-list control. Gambling-related measures derived from timeline follow-back as well as general levels of anxiety and depression were administered at baseline, termination, and 6 and 12 months posttermination. Treatment showed superiority in some areas over the no-treatment control in the short term, including the primary outcome measure. No differences were found between MI and CBGT at any point in time. Instead, both MI and CBGT produced significant within-group decreases on most outcome measures up to the 12-month follow-up. Both forms of intervention are promising treatments, but there is room for improvement in terms of both outcome and compliance.", "The objective of this study was to compare the effects of psychosocial interventions based on the modified reattribution model for somatizing patients in general practice (GP) with those of nonspecific psychosocial primary care (PPC) alone.\n Forty-two GPs were randomized, 23 into the intervention group (IG), who were trained in reattribution techniques, and 19 into the control group (CG). One hundred twenty-seven patients were included. Primary outcome measures were somatoform symptoms and quality of life.\n Multilevel modeling revealed a reduction of physical symptoms (P = .007), an improvement in physical functioning (P = .0172), and a reduction of depression (P = .0211) and anxiety (P = .0388) in the IG compared with the CG at the 3-month follow-up. However, results no longer remained significant after controlling for baseline and covariate variables besides a reduction of physical symptoms at 6-month follow-up (P = .029).\n Compared with nonspecific PPC, the effects of reattribution techniques were small and limited to physical symptoms.", "The effect of funding source on the outcome of randomized controlled trials has been investigated in several medical disciplines; however, psychiatry has been largely excluded from such analyses. In this article, randomized controlled trials of second generation antipsychotics in schizophrenia are reviewed and analyzed with respect to funding source (industry vs. non-industry funding).\n A literature search was conducted for randomized, double-blind trials in which at least one of the tested treatments was a second generation antipsychotic. In each study, design quality and study outcome were assessed quantitatively according to rating scales. Mean quality and outcome scores were compared in the industry-funded studies and non-industry-funded studies. An analysis of the primary author's affiliation with industry was similarly performed.\n Results of industry-funded studies significantly favored second generation over first generation antipsychotics when compared to non-industry-funded studies. Non-industry-funded studies showed a trend toward higher quality than industry-funded studies; however, the difference between the two was not significant. Also, within the industry-funded studies, outcomes of trials involving first authors employed by industry sponsors demonstrated a trend toward second generation over first generation antipsychotics to a greater degree than did trials involving first authors employed outside the industry (p=0.05).\n While the retrospective design of the study limits the strength of the findings, the data suggest that industry bias may occur in randomized controlled trials in schizophrenia. There appears to be several sources by which bias may enter clinical research, including trial design, control of data analysis and multiplicity/redundancy of trials." ]	In view of methodological deficiencies and the limited number of individuals studied, we have found no reliable evidence to support the use of psychological treatments and further trials are needed. Since the last version of this review, none of the new relevant studies have provided additional information to change the conclusions.
CD007339	[ "11113085", "20102716" ]	[ "Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: a double-blind, placebo-controlled trial.", "Pentoxifylline does not decrease short-term mortality but does reduce complications in patients with advanced cirrhosis." ]	[ "An earlier pilot study from our liver unit suggested benefit from treatment with pentoxifylline (PTX), an inhibitor of tumor necrosis factor (TNF), in severe acute alcoholic hepatitis. The aim of the present study was to evaluate this treatment in a larger cohort of patients.\n One hundred one patients with severe alcoholic hepatitis (Maddrey discriminant factor > or = 32) entered a 4-week double-blind randomized trial of PTX (400 mg orally 3 times daily) vs. placebo. Primary endpoints of the study were the effect of PTX on (1) short-term survival and (2) progression to hepatorenal syndrome. On randomization, there were no differences in demographic and clinical characteristics or laboratory values (including TNF) between the 2 groups.\n Twelve (24.5%) of the 49 patients who received PTX and 24 (46.1%) of the 52 patients who received placebo died during the index hospitalization (P = 0.037; relative risk, 0.59; 95% confidence interval, 0.35-0.97). Hepatorenal syndrome was the cause of death in 6 (50%) and 22 (91.7%) patients (P = 0.009; relative risk, 0.29; 95% confidence interval, 0.13-0.65). Three variables (age, creatinine level on randomization, and treatment with PTX) were independently associated with survival. TNF values on randomization were not predictive of survival; however, during the study period they increased markedly in nonsurvivors compared with survivors in both groups.\n Treatment with PTX improves short-term survival in patients with severe alcoholic hepatitis. The benefit appears to be related to a significant decrease in the risk of developing hepatorenal syndrome. Increasing TNF levels during the hospital course are associated with an increase in mortality rate.", "Pentoxifylline, an inhibitor of tumor necrosis factor-alpha, is given to patients with liver diseases, but its effects in patients with advanced cirrhosis are unknown. We performed a randomized, placebo-controlled, double-blind trial of its effects in patients with cirrhosis.\n A total of 335 patients with cirrhosis (Child-Pugh class C) were assigned to groups given either pentoxifylline (400 mg, orally, 3 times daily; n = 164) or placebo (n = 171) for 6 months. The primary end point was mortality at 2 months. Secondary end points were mortality at 6 months and development of liver-related complications.\n By 2 months, 28 patients in the pentoxifylline group (16.5%) and 31 in the placebo group (18.2%) had died (P = .84). At 6 months, 50 patients in the pentoxifylline group (30.0%) and 54 in the placebo group (31.5%) had died (P = .75). The proportions of patients without complications (eg, bacterial infection, renal insufficiency, hepatic encephalopathy, or gastrointestinal hemorrhage) were higher in the pentoxifylline group than in the placebo group at 2 months (78.6% vs 63.4%; P = .006) and 6 months (66.8% vs 49.7%; P = .002). The probability of survival without complications was higher in the pentoxifylline group than in the placebo group at 2 and 6 months (P = .04). In multivariate analysis, the factors associated with death were age, the Model for End-Stage Liver Disease score, and presence of early-stage carcinoma. Treatment with pentoxifylline was the only factor associated with liver-related complications.\n Although pentoxifylline does not decrease short-term mortality in patients with advanced cirrhosis, it does reduce the risk of complications.\n Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved." ]	The current available data may indicate a possible positive intervention effect of pentoxifylline on all-cause mortality and mortality due to hepatorenal syndrome, and conversely, an increase in serious and non-serious adverse events. However, the evidence is not firm; no conclusions can be drawn regarding whether pentoxifylline has a positive, negative, or neutral effect on participants with alcoholic hepatitis.

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