Split (3)

train · 3.75k rows

review_id stringlengths 8 8	pmid list	title list	abstract list	target stringlengths 56 2.23k
CD007464	[ "11013281", "11697833" ]	[ "Treatment of brain metastases of small-cell lung cancer: comparing teniposide and teniposide with whole-brain radiotherapy--a phase III study of the European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group.", "Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: a randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG)." ]	[ "Approximately 60% of patients with small-cell lung cancer (SCLC) develop brain metastases. Whole-brain radiotherapy (WBRT) gives symptomatic improvement in more than 50% of these patients. Because brain metastases are a sign of systemic progression, and chemotherapy was found to be effective as well, it becomes questionable whether WBRT is the only appropriate therapy in this situation.\n In a phase III study, SCLC patients with brain metastases were randomized to receive teniposide with or without WBRT. Teniposide 120 mg/m(2) was given intravenously three times a week, every 3 weeks. WBRT (10 fractions of 3 Gy) had to start within 3 weeks from the start of chemotherapy. Response was measured clinically and by computed tomography of the brain.\n One hundred twenty eligible patients were randomized. A 57% response rate was seen in the combined-modality arm (95% confidence interval [CI], 43% to 69%), and a 22% response rate was seen in the teniposide-alone arm (95% CI, 12% to 34%) (P<.001). Time to progression in the brain was longer in the combined-modality group (P=.005). Clinical response and response outside the brain were not different. The median survival time was 3.5 months in the combined-modality arm and 3.2 months in the teniposide-alone arm. Overall survival in both groups was not different (P=.087).\n Adding WBRT to teniposide results in a much higher response rate of brain metastases and in a longer time to progression of brain metastases than teniposide alone. Survival was poor in both groups and not significantly different.", "Concurrent platinum etoposide chemotherapy given in combination with hyperfractionated thoracic radiation therapy (HTRT) in limited disease (LD) small cell lung cancer (SCLC) is associated with a high response rate and significant prolongation of survival. Given these results, the Hellenic Cooperative Oncology Group (HeCOG) performed a multicenter randomized phase II study in patients with LD SCLC to evaluate the timing of HTRT (early vs. late) when given concurrently with chemotherapy.\n To be eligible for the study, patients were required to have histologically or cytologically proven LD SCLC, confined to one hemithorax and/or ipsilateral mediastinal or supraclavicular lymphnodes and absence of pleural effusion or controlateral supraclavicular lymphnode involvement. Moreover, patients had to have a good performance status and adequate haematological, liver and renal function. Patients with LD SCLC were randomized to receive HTRT either concurrently with the first (Group A) or with the fourth (Group B) cycle of chemotherapy. Chemotherapy consisted of carboplatin administered at an AUC of six given as an i.v. 1-hour-infusion immediately followed by etoposide at a dose of 100 mg/m2 i.v. as a two-hour infusion for three consecutive days every three weeks up to a total of six cycles. Prophylactic cranial irradiation was also given to patients achieving a complete response.\n 42 and 39 patients, were eligible for efficacy evaluation in group A and B respectively. The overall response rate was 76% in group A and 92.5% in group B (P = 0.07) with a complete response rate of 40.5% and 56.5%, respectively. After a median follow-up of 35 months, time to progression was 9.5 months in group A and 10.5 in group B (NS) while overall median survival was 17.5 and 17 months respectively (NS). The 2-year survival was 36% in group A and 29% in group B (NS) and the 3-year survival 22% and 13%, respectively (NS). The distant relapse rate was 38% in group A and 61% in group B (P = 0.046). Severe grade 3 4 anemia was recorded in 19% of group A and 12.5% of group B (NS), while severe leucopenia was recorded in 35.5% and 20.5% (P = 0.09) and neutropenic fever in 5% and 2.5% (NS), respectively. Severe thrombocytopenia did not differ significantly between the two treatment groups being 21.5% and 23%, respectively. Severe grade 2-3 esophageal toxicity was 19% in group A and 23% in group B (NS), while grade 3 lung toxicity was 5% and 7.5% (NS), respectively. No toxicity-related deaths were recorded.\n Concurrent administration of HTRT with carboplatin etoposide is associated with a high response and survival rate. Although a trend for higher response rate was recorded in the group of patients who received late HTRT, the overall median, 2-year and 3-year survival rates did not differ significantly between the two treatment groups. The toxicity of this promising therapeutic approach was acceptable. Comparative phase III studies with an adequate number of patients are recommended in order to answer this question." ]	Given the paucity of robust studies assessing the clinical effects of treatments, available evidence is insufficient to judge the effectiveness and safety of chemotherapy for the treatment of BM from SCLC. Published studies are insufficient to address the objectives of this review. According to the available evidence included in this review, chemotherapy does not improve specific brain PFS and OS in patients with SCLC. The combined treatment of teniposide and brain radiation therapy contributed to outcome in terms of increased complete remission and shorter time to progression (though not OS).
CD004577	[ "19525241", "10407930", "2489863", "16558388", "17261562", "453340" ]	[ "A pragmatic randomised trial of stretching before and after physical activity to prevent injury and soreness.", "The effects of preexercise stretching on muscular soreness, tenderness and force loss following heavy eccentric exercise.", "The effects of static stretching and warm-up on prevention of delayed-onset muscle soreness.", "Various treatment techniques on signs and symptoms of delayed onset muscle soreness.", "Ice-water immersion and delayed-onset muscle soreness: a randomised controlled trial.", "Effect of electromyographic feedback and static stretching on artificially induced muscle soreness." ]	[ "To determine the effects of stretching before and after physical activity on risks of injury and soreness in a community population.\n Internet-based pragmatic randomised trial conducted between January 2008 and January 2009.\n International.\n A total of 2377 adults who regularly participated in physical activity.\n Participants in the stretch group were asked to perform 30 s static stretches of seven lower limb and trunk muscle groups before and after physical activity for 12 weeks. Participants in the control group were asked not to stretch.\n Participants provided weekly on-line reports of outcomes over 12 weeks. Primary outcomes were any injury to the lower limb or back, and bothersome soreness of the legs, buttocks or back. Injury to muscles, ligaments and tendons was a secondary outcome.\n Stretching did not produce clinically important or statistically significant reductions in all-injury risk (HR=0.97, 95% CI 0.84 to 1.13), but did reduce the risk of experiencing bothersome soreness (mean risk of bothersome soreness in a week was 24.6% in the stretch group and 32.3% in the control group; OR=0.69, 95% CI 0.59 to 0.82). Stretching reduced the risk of injuries to muscles, ligaments and tendons (incidence rate of 0.66 injuries per person-year in the stretch group and 0.88 injuries per person-year in the control group; HR=0.75, 95% CI 0.59 to 0.96).\n Stretching before and after physical activity does not appreciably reduce all-injury risk but probably reduces the risk of some injuries, and does reduce the risk of bothersome soreness.\n anzctr.org.au 12608000044325.", "The present study sought to investigate the effects of preexercise stretching on delayed onset muscle soreness (DOMS), i.e. soreness, tenderness and loss of muscle force, that usually occurs after strenuous or unaccustomed eccentric exercise. Ten female volunteers performed 10 sets of 10 maximal isokinetic eccentric contractions for knee flexion with both legs after a 5-min ergometer cycling warm-up. Prior to the exercise for one leg, randomly chosen, 4 x 20 s of static stretching for the hamstring muscle group was implemented. Rated soreness, tenderness on algometer pressure and loss of maximal eccentric contractile force was evaluated preexercise and 24, 48 and 96 h postexercise. The exercise bout produced severe DOMS, with parameters peaking and troughing at 48 h postexercise. However, no significant differences were found, regarding any of the parameters, when comparing stretched and nonstretched legs. The present study thus suggests that preexercise static stretching has no preventive effect on the muscular soreness, tenderness and force loss that follows heavy eccentric exercise.", "It has been suggested in the lay literature that static stretching and/or warm-up will prevent the occurrence of Delayed-Onset Muscle Soreness (DOMS). The primary purpose of this study was to determine the effects of static stretching and/or warm-up on the level of pain associated with DOMS. Sixty-two healthy male and female volunteers were randomly assigned to four groups: (a) subjects who statically stretched the quadriceps muscle group before a step, (b) subjects who only performed a stepping warm-up, (c) subjects who both stretched and performed a stepping warm-up prior to a step test, and (d) subjects who only performed a step test. The step test (Asmussen, 1956) required subjects to do concentric work with their right leg and eccentric work with their left leg to voluntary exhaustion. Subjects rated their muscle soreness on a ratio scale from zero to six at 24-hour intervals for 5 days following the step test. A 4x2x2 ANOVA with repeated measures on legs and Duncan's New Multiple Range post-hoc test found no difference in peak muscle soreness among the groups doing the step test or for gender (p greater than .05). There was the expected significant difference in peak muscle soreness between eccentrically and concentrically worked legs, with the eccentrically worked leg experiencing greater muscle soreness. We concluded that static stretching and/or warm-up does not prevent DOMS resulting from exhaustive exercise.", "Eccentric activities are an important component of physical conditioning and everyday activities. Delayed onset muscle soreness (DOMS) can result from strenuous eccentric tasks and can be a limiting factor in motor performance for several days after exercise. An efficacious method of treatment for DOMS would enhance athletic performance and hasten the return to activities of daily living. The purpose of this study was to identify a treatment method which could assist in the recovery of DOMS. In the selection of treatment methods, emphasis was directed toward treatments that could be rendered independently by an individual, therefore making the treatment valuable to an athletic trainer in team setting. DOMS was induced in 70 untrained volunteers via 15 sets of 15 eccentric contractions of the forearm extensor muscles on a Lido isokinetic dynamometer. All subjects performed a pilot exercise bout for a minimum of 9 weeks before data collection to assure that DOMS would be produced. Data were collected on 15 dependent variables: active and passive wrist flexion and extension, forearm girth, limb volume, visual analogue pain scale, muscle soreness index, isometric strength, concentric and eccentric wrist total work, concentric and eccentric angle of peak torque. Data were collected on six occasions: pre- and post-induced DOMS, 20 minutes after treatment, and 24, 48, and 72 hours after treatment. Subjects were randomly assigned to 1 of 7 groups (6 treatment and 1 control). Treatments included a nonsteroidal anti-inflammatory drug, high velocity concentric muscle contractions on an upper extremity ergometer, ice massage, 10-minute static stretching, topical Amica montana ointment, and sublingual A. montana pellets. A 7 x 6 ANOVA with repeated measures on time was performed on the delta values of each of the 15 dependent variables. Significant main effects (p < .05) were found for all of the dependent variables on time only. There were no significant differences between treatments. Therefore, we conclude that none of the treatments were effective in abating the signs and symptoms of DOMS. In fact, the NSAID and A. montana treatments appeared to impede recovery of muscle function.", "To determine if ice-water immersion after eccentric quadriceps exercise minimises the symptoms of delayed-onset muscle soreness (DOMS).\n A prospective randomised double-blind controlled trial was undertaken. 40 untrained volunteers performed an eccentric loading protocol with their non-dominant leg.\n Participants were randomised to three 1-min immersions in either ice water (5+/-1 degrees C) or tepid water (24 degrees C).\n Pain and tenderness (visual analogue scale), swelling (thigh circumference), function (one-legged hop for distance), maximal isometric strength and serum creatine kinase (CK) recorded at baseline, 24, 48 and 72 h after exercise. Changes in outcome measures over time were compared to determine the effect of group allocation using independent t tests or Mann-Whitney U tests.\n No significant differences were observed between groups with regard to changes in most pain parameters, tenderness, isometric strength, swelling, hop-for-distance or serum CK over time. There was a significant difference in pain on sit-to-stand at 24 h, with the intervention group demonstrating a greater increase in pain than the control group (median change 8.0 vs 2.0 mm, respectively, p = 0.009).\n The protocol of ice-water immersion used in this study was ineffectual in minimising markers of DOMS in untrained individuals. This study challenges the wide use of this intervention as a recovery strategy by athletes.", "Thirty-six male subjects aged 18 to 26 years were assigned at random to one of three treatment groups: biofeedback, static stretch, and control. Muscle soreness was produced in all subjects by an 80% maximal eccentric contraction of the biceps brachii. The subjects in the biofeedback group applied auditory electromyographic (EMG) feedback at 6, 25, 30, 49, and 54 hours after the exercise, and the stretch group applied static stretch to the exercised arm at the same time periods. Observations of EMG activity and perceived pain level were made immediately before and after exercise, and at 24, 48, and 72 hours following exercise. When compared with a control group, both auditory biofeedback and static stretching significantly reduced EMG muscle activity but had no significant effect on perceived pain. The EMG activity and perceived pain of the subjects in each treatment group significantly differed across observations." ]	The evidence from randomised studies suggests that muscle stretching, whether conducted before, after, or before and after exercise, does not produce clinically important reductions in delayed-onset muscle soreness in healthy adults.
CD003511	[ "10453830", "14747165", "16225575", "11870141", "12351534", "20005647", "11157836" ]	[ "Randomised trial comparing expectant with medical management for first trimester miscarriages.", "A randomized controlled trial comparing medical and expectant management of first trimester miscarriage.", "First trimester threatened miscarriage treatment with human chorionic gonadotrophins: a randomised controlled trial.", "A randomized, double-blind, placebo-controlled trial of intravenous immunoglobulin in the prevention of recurrent miscarriage: evidence for a therapeutic effect in women with secondary recurrent miscarriage.", "Improving cycle control in progestogen-only contraceptive pill users by intermittent treatment with a new anti-progestogen.", "Dydrogesterone in threatened miscarriage: a Malaysian experience.", "A prospective randomized control trial comparing medical and surgical treatment for early pregnancy failure." ]	[ "To compare the efficacy of antiprogesterone (mifepristone) in combination with a synthetic prostaglandin E1 analogue (misoprostol) for outpatient treatment of miscarriages.\n One hundred and twenty-two women with first trimester miscarriages.\n The women were randomised to treatment with mifepristone 400 mg orally followed by a single oral dose of 400 microg misoprostol 48 hours later (n = 60) or expectant management (n = 62). Women were re-evaluated five days later. If retained intrauterine products of conception were found with an antero-posterior diameter above 15 mm on transvaginal ultrasound, surgical evacuation was performed.\n Eighty-two percent of the women randomised to pharmacological treatment and 76% of those randomised to expectant management had an empty uterine cavity after five days. Convalescence time was 1.8 days longer for women randomised to pharmacological treatment. Pain, bleeding, complications, and satisfaction with the treatment did not differ between the groups.\n Most cases of spontaneous incomplete miscarriage will become a complete miscarriage without intervention. This study shows that outpatient treatment with a combination of antiprogesterone and a prostaglandin E1 analogue did not increase the rate of complete miscarriage, compared with expectancy alone, by a clinical important degree.", "We aimed to determine whether outpatient treatment of miscarriage with vaginal misoprostol is more effective than expectant management in reducing the need for surgical evacuation of retained products of conception (ERPC).\n Of 131 eligible women with first trimester miscarriage, 104 agreed to randomization to either 600 microg misoprostol or placebo intravaginally. They were assessed the following day and administered a second dose of their allocated treatment if miscarriage was not complete. Those not successful after two doses were seen on day 7, and, if miscarriage was not complete, an ERPC was performed.\n The success rate of medical management was 88.5% (46/52) compared with 44.2% (23/52) for expectant management. There was no significant difference in success rate (100 versus 85.7%) in women treated with an incomplete miscarriage. Women with early pregnancy failure had a success rate of 87% with misoprostol compared with 29% with expectant management [odds ratio (OR) 15.96; 95% confidence interval (CI) 5.26, 48.37]. The complete miscarriage rate was achieved quicker in the medical group than the expectant group by day 1 (32.7 versus 5.8%) and by day 2 (73.1 versus 13.5%) of treatment. There were no differences in side-effects, bleeding duration, analgesia use, pain score and satisfaction with treatment. Women in the expectant group made more outpatient visits (5.06 versus 4.44%; OR = -0.62, 95% CI -1.04, -0.19). More women in the medical group (90.4 versus 73.1%; OR 1.26, 95% CI 1.05, 1.50) would elect the same treatment in the future.\n Medical management using 600 microg misoprostol vaginally is more effective than expectant management of early pregnancy failure. Misoprostol did not increase the side-effect profile and patient acceptability was superior to expectant management.", "To determine whether administration of exogenous human chorionic gonadotrophin (hCG) treatment improve the pregnancy outcome in first trimester threatened miscarriages.\n A prospective, double blind, randomised, placebo-controlled trial.\n The Early Pregnancy Assessment Unit, Royal Bolton Hospital, Bolton, United Kingdom.\n One hundred and eighty-three women with vaginal bleeding and a viable fetus seen on ultrasound scan (USS) in the first 12 weeks of pregnancy.\n The patients were randomised to receive either hCG or placebo treatment until 14 weeks of gestation.\n The primary objective of the trial was to determine the miscarriage rate in the hCG arm compared from the placebo arm.\n Of the 183 cases, 87 were randomised to treatment with hCG while 96 were randomised to receive a placebo. Forty-seven (25%) did not comply with the study protocol. The mean [SD] gestational age at presentation was 7 [1.33] weeks. The mean [SD] age of women in study was 27 [5] years in the placebo and 28 [5] in the hCG group. The mean body mass index (kg/m(2)) was 25 [5] in the study. The number of patients actively bleeding per vaginum at presentation was 85 (93%) in placebo group and 79 (96%) in the hCG group. The median number of hCG or placebo injections for both groups was 7. Ten women (11%) in the placebo group proceeded to have a complete miscarriage, as did 10 women (12%) in the hCG group, relative risk (RR) [95% confidence interval (CI)] of 1.1 (0.63-1.6).\n Our study showed no evidence of a difference in the outcome of threatened miscarriages when treated with hCG in the first trimester, this may be because our study sample size was small and follow up was suboptimal. A large, randomised, multicentre trial is still needed to establish the usefulness of hCG treatment in cases of threatened miscarriage.", "Previous trials of intravenous immunoglobulin (IvIg) treatment of women with recurrent miscarriage (RM) have provided diverging results. This may be due to different inclusion criteria and suboptimal treatment protocols in some trials.\n According to a computer-generated list, 58 women with at least four unexplained miscarriages were randomly assigned to receive infusions of high doses of IvIg or placebo starting as soon as the pregnancy test was positive.\n In the intention-to-treat analysis, a 45% live birth rate was found in both allocation groups. In patients with secondary RM, 50% in the treatment group and 23% in the placebo group had successful pregnancies (P = not significant). When data from the present and a previous placebo-controlled trial of the same treatment were combined, 15/26 (58%) of the patients with secondary RM in the treatment group versus 6/26 (24%) in the placebo group had successful outcomes (P < 0.02). Only 7% of the karyotyped abortuses were abnormal.\n IvIg may improve pregnancy outcome in patients with secondary RM. A new placebo-controlled trial focusing on this subgroup should be conducted to confirm the results.", "The safety and efficacy of the anti-progestogen Org 31710 in improving cycle control in healthy women using the desogestrel progestogen-only pill was investigated in this randomized, double-blind, placebo-controlled study.\n A total of 103 women using the 75 micro g desogestrel progestogen-only pill daily also received either 150 mg Org 31710 or placebo once every 28 days, starting on day 1, for a duration of 4-7 treatment cycles.\n The percentage of women with bleeding or spotting (B/S) every day in the placebo group was on average 30% during the whole treatment period and no days without reported B/S occurred. In contrast, a cyclic pattern was observed for the Org 31710 group; a peak incidence of B/S was observed on day 3 or 4 of each cycle, followed by a sharp decrease on cycle days 9-15. Compared with controls, less subjects in the Org 31710 group reported irregular, frequent or prolonged bleeding. These differences were clearly observed in the initial cycles, but were somewhat less pronounced during the later cycles of the treatment period. A relatively high incidence of B/S episodes starting in the second section of the cycle was also observed.\n The addition of Org 31710 once a month improved cycle control in women using daily treatment with 75 micro g desogestrel.", "Threatened miscarriage is a common problem during pregnancy.\n The aim of this prospective, open, randomised study was to determine whether dydrogesterone was more effective than conservative management alone in preventing miscarriage in women with vaginal bleeding up to week 16 of pregnancy. Women were excluded if they had a history of recurrent miscarriage. A total of 191 women were randomised to dydrogesterone (40 mg stat followed by 10mg twice daily) or conservative management (control group). The treatment was considered successful if the pregnancy continued beyond 20 weeks of gestation.\n The success rate in the dydrogesterone group was statistically significantly higher than that in the control group (87.5% vs. 71.6%; p<0.05). Miscarriage occurred in 12.5% of women in the dydrogesterone group compared with 28.4% in the control group (p<0.05). There were no differences between the groups with regard to the incidence of Caesarean section, placenta praevia, antepartum haemorrhage, preterm labour (weeks 28-36), pregnancy-induced hypertension or low birth weight (<2500 g) babies. There were no intrauterine deaths or congenital abnormalities in either group.\n Compared with conservative management, dydrogesterone had beneficial effects on maintaining pregnancy in women with threatened miscarriage.\n Copyright 2009 Elsevier Ireland Ltd. All rights reserved.", "A prospective randomized control trial was designed to assess the effectiveness of single dose, 800 microg misoprostol administered p.v. compared with surgical evacuation for the treatment of early pregnancy failure. A total of 80 women with a diagnosis of early pregnancy failure were randomized to study (vaginal misoprostol) and control (surgical curettage) groups. Success of treatment, side-effects as assessed during, immediately after and 10 days after treatment, and patient satisfaction were compared. Intravaginal misoprostol was successful in 82.5% (33 out of 40) of the patients. None of the control group patients required a repeat evacuation. The number of patients who experienced significant abdominal pain following treatment did not differ between the groups. The duration of pain was shorter in the control group; however, they required more analgesics during this short period. The number of patients with significant vaginal bleeding, the duration or severity of bleeding did not show any significant difference between the groups. All 33 patients in the study group who had successful treatment expressed satisfaction, whereas only 58% of the control group did so. In conclusion this randomized control study demonstrated the efficacy and safety of the administration of 800 microg of misoprostol p.v. for the management of early pregnancy failure." ]	There is no evidence to support the routine use of progestogen to prevent miscarriage in early to mid-pregnancy. However, there seems to be evidence of benefit in women with a history of recurrent miscarriage. Treatment for these women may be warranted given the reduced rates of miscarriage in the treatment group and the finding of no statistically significant difference between treatment and control groups in rates of adverse effects suffered by either mother or baby in the available evidence. Larger trials are currently underway to inform treatment for this group of women.
CD005383	[ "375171", "6988006" ]	[ "Risk of respiratory distress syndrome after prenatal dexamethasone treatment.", "The influence of betamethasone and orciprenaline on the incidence of respiratory distress syndrome in the newborn after preterm labour." ]	[ "A prospective double-blind randomized clinical trial was carried out to determine whether glucocorticoid treatment reduces the risk of respiratory distress syndrome (RDS) in prematurely born infants. There were 127 infants born to 122 mothers who received either steroid (dexamethasone phosphate) or placebo. No differences between groups occurred in risk factors for RDS (eg, prepartum asphyxia, male sex, cesarean section). When those who received a full course of dexamethasone therapy were compared with those who received placebo, a significant reduction was found in risk, severity, and deaths due to RDS. An increased incidence of infection in mothers treated with steroid was evident, particularly after premature rupture of membranes. We conclude that steroids are effective in reducing risk of RDS, but safer and more efficacious approaches for the prevention of RDS should be sought.", "In a randomized double-blind trial on antenatal corticosteroid treatment for the prevention of respiratory distress syndrome (RDS) a corticosteroid related beneficial effect was found. Possibly of more significance was the finding that the children born within 12 hours of their mother's admission to hospital showed a higher incidence of RDS than those born between 12 hours and one week after admission even in the placebo and untreated groups. Bèta-adrenergic drugs seemed to exert no other influence on the occurrence of RDS than can be explained by the delay of delivery. Prolonged ruptured membranes appeared to decrease the incidence of RDS to the same extent as other symptoms of threatened preterm labour." ]	Preterm infants with RDS are unlikely to benefit from AT treatment and may be harmed.
CD002310	[ "14512127", "14694242", "10868712", "10390394", "2669554", "11555383", "8947070", "18475734", "3662586", "11182010", "10190915", "7664857", "9517598", "10926345", "10542974", "16119035", "16889952", "7491551", "15805993", "18370529", "10325895", "14716965", "7648372", "22111718", "1514669", "3547757", "6958478", "14720008", "3512282", "12765916", "8290745", "8215522", "9215245", "11112113", "15878495", "11101186", "9109702", "10329812", "3307881", "8879892", "9564798", "10390389" ]	[ "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.", "Time course of action of two inhaled corticosteroids, fluticasone propionate and budesonide.", "Comparable effects of inhaled fluticasone propionate and budesonide on the HPA-axis in adult asthmatic patients.", "Systemic effects of inhaled fluticasone propionate and budesonide in adult patients with asthma.", "Comparison of dose-response effects of inhaled beclomethasone dipropionate and budesonide in the management of asthma.", "Improved safety with equivalent asthma control in adults with chronic severe asthma on high-dose fluticasone propionate.", "Fluticasone propionate compared with budesonide: a double-blind trial in asthmatic children using powder devices at a dosage of 400 microg x day(-1).", "A blinded comparison of fluticasone propionate with budesonide via powder devices in adult patients with moderate-to-severe asthma: a clinical evaluation.", "Comparison of budesonide and beclomethasone dipropionate for treatment of asthma.", "Comparison of the systemic effects of fluticasone propionate and budesonide given by dry powder inhaler in healthy and asthmatic subjects.", "Efficacy and safety of high-dose inhaled steroids in children with asthma: a comparison of fluticasone propionate with budesonide.", "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.", "Safety and efficacy of fluticasone and beclomethasone in moderate to severe asthma. Belgian Multicenter Study Group.", "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.", "The effect of high-dose fluticasone propionate and budesonide on lung function and asthma exacerbations in patients with severe asthma.", "Effects of inhaled corticosteroids on growth in asthmatic children: a comparison of fluticasone propionate with budesonide.", "Potency ratio fluticasone propionate (Flixotide Diskus)/budesonide (Pulmicort Turbuhaler).", "Comparison of fluticasone propionate and beclomethasone dipropionate on direct and indirect measurements of bronchial hyperresponsiveness in patients with stable asthma.", "Protection by budesonide and fluticasone on allergen-induced airway responses after discontinuation of therapy.", "Cost effectiveness of fluticasone and budesonide in patients with moderate asthma.", "Addition of salmeterol versus doubling the dose of fluticasone propionate in patients with mild to moderate asthma.", "[A fixed combination of fluticasone and salmeterol permits better control of asthma than a beclomethasone dipropionate and montelukast combination].", "Budesonide inhaled via Turbuhaler: a more effective treatment for asthma than beclomethasone dipropionate via Rotahaler.", "Daily or intermittent budesonide in preschool children with recurrent wheezing.", "High-dose inhaled steroids in the management of asthma. A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness and the adrenal function.", "Comparison of two high dose corticosteroid aerosol treatments, beclomethasone dipropionate (1500 micrograms/day) and budesonide (1600 micrograms/day), for chronic asthma.", "Twice daily inhalation of a new corticosteroid, budesonide, in the treatment of chronic asthma.", "Combination therapy with single inhaler budesonide/formoterol compared with high dose of fluticasone propionate alone in patients with moderate persistent asthma.", "High-dose inhaled budesonide in treatment of severe steroid-dependent asthma.", "Fluticasone propionate in asthma: a long term dose comparison study.", "Evaluation of fluticasone propionate (500 micrograms day-1) administered either as dry powder via a Diskhaler inhaler or pressurized inhaler and compared with beclomethasone dipropionate (1000 micrograms day-1) administered by pressurized inhaler.", "Comparison of the efficacy and safety of inhaled fluticasone propionate 200 micrograms/day with inhaled beclomethasone dipropionate 400 micrograms/day in mild and moderate asthma.", "A randomized, double-blind dose reduction study to compare the minimal effective dose of budesonide Turbuhaler and fluticasone propionate Diskhaler.", "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.", "Improvement of asthma control with beclomethasone extrafine aerosol compared to fluticasone and budesonide.", "Efficacy and safety of dry powder fluticasone propionate in children with persistent asthma.", "Comparative efficacy and safety of twice daily fluticasone propionate powder versus placebo in the treatment of moderate asthma.", "A comparison of multiple doses of fluticasone propionate and beclomethasone dipropionate in subjects with persistent asthma.", "A comparison of inhaled budesonide and beclomethasone dipropionate in childhood asthma.", "Effectiveness of fluticasone propionate in patients with moderate asthma: a dose-ranging study.", "Rapid induction of clinical response with a short-term high-dose starting schedule of budesonide nebulizing suspension in young children with recurrent wheezing episodes.", "The effect of inhaled fluticasone propionate in the treatment of young asthmatic children: a dose comparison study." ]	[ "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.", "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.", "This randomized, double-blind, double-dummy, multicentre cross-over study compared the effects on the hypothalamic-pituitary-adrenal (HPA) axis of fluticasone propionate (750 microg twice daily given via the Diskus) and budesonide (800 microg twice daily given via the Turbuhaler). Two treatment periods of 2 weeks each were preceded by a 2-week run-in period and separated by a 2-week washout period. During run-in and washout, patients received beclomethasone dipropionate (BDP) or budesonide at a constant dose of 1500-1600 microg day(-1). Sixty patients aged 18-75 years with moderate to severe asthma not fully controlled by treatment with 1500-1600 microg day(-1) budesonide or BDP entered run-in and 45 completed the study. HPA axis suppression was assessed by morning serum cortisol (area under the curve from 08.00 to 10.30 hours) and 12-h nocturnal urinary cortisol excretion, measured at the end of run-in (baseline 1), at the end of washout (baseline 2), and at the end of each treatment period. Neither budesonide nor fluticasone produced significant suppression of either parameter compared to baselines. Only a few patients had serum-cortisol and urinary cortisol values below the normal range, before and after treatment. This shows that the patients did not have adrenal suppression before entering the study. The ratio between the AUC serum cortisol measured after fluticasone treatment and after budesonide treatment was 0.99 (95% CI 0.92-1.06), indicating equivalent effects on the HPA axis. This result was achieved after having omitted two patients' results, due to their very sensitive reaction to budesonide, but not to fluticasone. Two exacerbations of acute asthma occurred during budesonide treatment and none during fluticasone treatment. Both treatments were well tolerated. In conclusion, budesonide 1600 microg day(-1) via Turbuhaler and fluticasone propionate 1500 microg day(-1) via Diskus had no clinical effects on the HPA axis in patients with moderate to severe asthma.", "We assessed the systemic effects of budesonide (BUD) and fluticasone propionate (FP) in 23 patients with asthma, using a double-blind, placebo-controlled, double-dummy, and cross-over design. The following five treatments were given in a randomized order for 1 wk with a washout period in between of 2 wk: (1) placebo; (2) FP, 200 micrograms twice a day, inhaled from a Diskhaler; (3) FP, 1,000 micrograms twice a day, inhaled from a Diskhaler; (4) BUD, 200 micrograms twice a day, inhaled from a Turbuhaler; and (5) BUD, 800 micrograms twice a day, inhaled from a Turbuhaler. The primary variable was the area under the curve of serum cortisol versus time (AUC0-20), derived from serum samples taken every 2 h over a 20-h period following the last evening dose at 10:00 P.M. The lower doses of BUD and FLU did not cause any adrenal suppression. Compared with placebo, however, FP (1, 000 micrograms, twice daily and BUD (800 micrograms, twice daily) decreased the AUC0-20 by 34 and 16%, respectively. Fluticasone (1,000 micrograms, twice daily) was more suppressive than BUD (800 micrograms, twice daily) (p = 0.0006). The FEV1, measured the morning after the last inhalation, was significantly higher after the active treatments, compared with placebo (p < 0.02), but did not differ between all active treatments. We conclude that high doses of BUD and FP (in particular the latter), inhaled via their respective dry powder inhalers for 1 wk, result in a measurable systemic activity in patients with asthma.", "The dose-response effects of inhaled beclomethasone dipropionate (BDP) and budesonide (BUD) administered b.i.d. with the aid of metered dose aerosols were studied in 128 patients (67 men and 61 women, mean age 53 years) suffering from asthma bronchiale. The study was designed as a multi-centre, double-blind, four-period cross-over study, followed by a single-blind double placebo period. BDP was administered in doses of 400 and 1000 micrograms, and BUD in doses of 400 and 800 micrograms. The results in terms of peak expiratory flow (PEF) in the morning and evening, daily symptoms score and use of inhaled beta 2-agonists did not reveal any clinically significant differences between the drugs or between high (800 micrograms BUD, 1000 micrograms BDP) and low (400 micrograms BUD/BDP) doses. However, statistically significant differences were recorded for the corresponding parameters when comparing the placebo with preceding steroid periods. Adverse effects consisting mainly of oropharyngeal candidiasis, hoarseness and cough occurred in 54 of 468 treatment months (12%). The carry-over effects of inhaled steroids are longer lasting than was previously assumed.", "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.", "The aim of this study was to compare fluticasone propionate (FP) with budesonide (BUD) at a dose of 400 microg x day(-1) in the treatment of children with asthma. Two hundred and twenty nine children with mild-to-moderate asthma, currently receiving 200-400 microg x day(-1) of inhaled corticosteroid, were randomized to receive either 400 microg x day(-1) of FP from the Diskhaler (registered trade mark of the Glaxo Group of Companies) or 400 microg x day(-1) of BUD from the Turbuhaler (registered trade mark of Astra Pharmaceuticals Ltd) for 8 weeks, in a parallel-group, double-blind, double-dummy study. Primary efficacy was assessed by measurement of daily peak expiratory flow (PEF). In addition, pulmonary function tests were performed at each clinic visit and a self-administered patient-centred questionnaire was completed by one parent of each patient at the start and end of study treatment. Mean morning PEF increased following treatment both with FP and BUD, but was significantly higher following treatment with FP during Weeks 1-4 (p=0.015) and Weeks 1-8 (p=0.019). Similar results were found for mean evening PEF and percentage predicted morning and evening PEF. Children receiving FP experienced significantly less disruption in their physical activities (i.e. sports, games) because of their asthma compared to children treated with BUD (p=0.03). Mean cortisol levels increased in both groups, but the increase was significantly higher in the FP group at 4 weeks (p=0.022). Serum and urine markers of bone formation and resorption changed very little and showed no consistent pattern of change. Fluticasone propionate at a dosage of 400 microg x day(-1) from the Diskhaler provided a more rapid and greater improvement in lung function in children with mild-to-moderate asthma than BUD 400 microg day(-1) from the Turbuhaler. Both treatments were well-tolerated, with a similar safety profile.", "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.", "Beclomethasone dipropionate (BDP) and budesonide (BUD) were each given in a dose of 200 micrograms twice daily by metered dose inhaler to 10 asthmatic children already dependent on treatment with steroids. In a double blind randomised crossover study each course lasted one month. No clinically important differences were found between the two treatments when symptom scores, symptom free days, additional use of salbutamol, and results of lung function tests were considered. Metyrapone mildly reduced the plasma concentration of 11-deoxycortisol in two patients during treatment with budesonide, and in four during treatment with beclomethasone. It is concluded that although they are usually safe, both drugs may cause mild adrenal suppression when given in a dose of 200 micrograms twice daily.", "The potential for long term adverse effects from inhaled corticosteroids relates to their systemic absorption, usually assessed from proxy markers in short term studies. When fluticasone propionate and budesonide have been compared in this way the results have been inconsistent. To determine whether this is because of the subjects studied or the sensitivity of the systemic marker used, we have compared the effects of fluticasone propionate and budesonide in healthy and asthmatic subjects and investigated the effect of treatment on three systemic markers.\n Forty six healthy subjects were randomised to receive inhaled fluticasone propionate 1500 microg/day (via an Accuhaler), budesonide 1600 microg/day (via a Turbuhaler), or placebo; 31 subjects with moderately severe asthma were randomised to receive the same doses of fluticasone propionate or budesonide but not placebo. Systemic effects in healthy and asthmatic subjects were compared after 7 days. Treatment was continued for another 21 days in the subjects with asthma when systemic effects and asthma control were assessed.\n At baseline healthy subjects had higher urinary levels of total cortisol metabolites (TCM) than subjects with asthma. After 7 days of treatment with fluticasone propionate urinary TCM levels in the healthy subjects were significantly lower than in the subjects with asthma (mean difference between groups 1663 microg/day, 95% CI 328 to 2938). This was not the case with budesonide, however, where urinary TCM levels in the healthy subjects remained above those in the asthmatic subjects (mean difference between groups 1210 microg/day, 95% CI -484 to 2904). Urinary TCM levels were considerably more sensitive to the effects of inhaled corticosteroids than morning serum cortisol or osteocalcin concentrations. Only budesonide reduced the serum level of osteocalcin.\n When given by dry powder inhaler for 7 days, fluticasone propionate 1500 microg/day has a greater effect on the hypothalamic-pituitary-adrenal axis in healthy subjects than in subjects with asthma, but this is not the case for budesonide 1600 microg/day. These findings, together with the differences in sensitivity between systemic markers, explain many of the discrepancies in the literature.", "To compare the efficacy and adverse effects of inhaled fluticasone propionate (FP), 400 microgram/d, with those of budesonide (BUD), 800 microgram/d, in children with moderate to severe asthma.\n Three hundred thirty-three children, ages 4 to 12 years, receiving inhaled corticosteroids were enrolled in a double-blind, double-dummy, randomized, parallel-group study. After a 2-week run-in phase, 166 children received FP and 167 received BUD for 20 weeks. The primary outcome variable was mean morning peak expiratory flow; the 2 treatments were to be regarded as equivalent if the 90% CI for the treatment difference was within +/- 15 L/min. Pulmonary function, height, and diary cards were assessed at each visit; and morning serum cortisol levels were determined before and after treatment.\n Baseline peak expiratory flow was similar, FP 236 +/- 72 (SD) L/min and BUD 229 +/- 74, increasing after treatment to 277 +/- 41 and 257 +/- 28, a difference between treatments of 12 L/min (90% CI 6-19 L/min; P =.002). Symptom control and use of rescue medication were the same. Cortisol levels after treatment were 199 nmol/L (FP) and 183 nmol/L (BUD) (treatment ratio = 1.09; 90% CI 0.98-1.21; P =.172). Linear growth was less in those receiving BUD (mean difference, 6.2 mm; 95% CI 2.9-9.6; P =.0003).\n FP at half the dose was superior to BUD in improving peak expiratory flow and comparable in controlling symptoms. Growth was reduced with BUD compared with FP, but there was no difference in serum cortisol suppression or hepatic or renal function.", "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)", "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.", "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.", "The purpose of this study was to investigate the comparative efficacy and safety of equal doses of inhaled fluticasone propionate (FP) and inhaled budesonide (BUD) using their respective dry powder inhalers in a population of severe asthmatics requiring high doses of inhaled corticosteroid. This double-blind double-dummy parallel-group study compared the effects of 24 weeks of treatment with FP (2000 micrograms daily via a Diskhaler inhaler; Glaxo Wellcome, Evreux, France) and BUD (2000 micrograms daily via a Turbuhaler inhaler; Astra Pharmaceuticals, Rijswijka, Netherlands) on lung function and asthma exacerbations in 395 patients with asthma. FP was statistically significantly superior to BUD with respect to the percentage of symptom-free days (P = 0.02), the incidence of days free from rescue bronchodilator usage (P = 0.02) and the distribution of change in peak expiratory flow (PEF) expressed as a percentage of the predicted PEF (P = 0.04). During the treatment period FP was statistically significantly superior to BUD for change in forced expiratory volume in 1 sec (FEV1) at 8, 16 and 24 weeks, change in the median daytime symptom score during weeks 5-16, for incidence of symptom-free days and incidence of days free from rescue bronchodilator usage during weeks 17-24. There was no significant difference between FP and BUD with respect to the number of patients experiencing one or more asthma exacerbation (33.8 and 28.4% of patients, respectively). There was, however, evidence that the exacerbations were clinically less severe in patients treated with FP, in that the time to resolution was quicker (11.0 vs. 14.7 days; P = 0.035), mean duration of all exacerbations (for an individual patient) tended to be shorter (18.5 vs. 23.6 days; P = 0.12), the time off work was reduced (4.2 vs. 7.6 days; P = 0.012) and the lowest PEF recorded during the exacerbation was higher (301 vs. 263 l min-1; P = 0.07). There were no clinically relevant differences in the safety (serum cortisol levels, markers of bone turnover, adverse events) of FP and BUD at these microgram equivalent doses. The patients recruited into this study, in retrospect, probably had no need for such high doses of inhaled corticosteroid but, irrespective of this, FP at microgram equivalent doses showed evidence of superior efficacy to BUD with respect to lung function and severity of asthma exacerbations without producing any greater adverse systemic effect.", "In asthmatic children inhaled corticosteroids are widely used. However, there are some concerns about the systemic adverse effects of these drugs, especially in the growing child. We performed this prospective study in order to compare the effects of 400 microg/day of budesonide (BUD) and 250 microg/day of fluticasone propionate (FP) on growth in prepubertal (aged 4-11.5 years), moderate persisting asthmatic children. One hundred patients (51 boys and 49 girls), who were randomized into two groups, were recruited for the study. The first group was treated with BUD, 2X 200 microg/day, and the second group was treated with FP, 2X 125 microg/day, by using a medium-size volume-spacer metered-dose inhaler. Growth in children with asthma who were treated by inhaled corticosteroids was calculated by growth velocity over a 12-month period. Comparisons between treatment groups were calculated by t-test and chi-square test. There were no significant differences between BUD and FP groups for sex, age, first height, and growth velocity. Moderate persisting, prepubertal asthmatic children treated with 250 microg/day of FP appeared to have no different linear growth than those children who received 400 microg/day of BUD.", "In the choice of, or switch between, various inhaled corticosteroids (ICS) it is important to know equipotent doses for clinical treatment effects of the alternatives. Various ICS do have different inherent potency. Further, the ICS are delivered from inhalers that may differ markedly in output characteristics and drug delivery to intrapulmonary airways. Therefore, clinical efficacy comparisons must include drug-inhaler comparisons. We estimated the therapeutic potency ratio of the Flixotide Diskus (fluticasone propionate, FP) and the Pulmicort Turbuhaler (budesonide, BUD) in steroid-naive asthma patients, using a dose-reduction technique (FP 500-0 mcg/day, BUD 800-0 mcg/day). The dose defining end point was loss of asthma control in this paper denoted as exacerbation. In total, 282 patients with proven asthma were enrolled in the study, and 103 in the FP group and 98 in the BUD group completed the study per protocol. In total, 80 patients in the FP-group and 79 in the BUD-group experienced a dose defining exacerbation. The exacerbation frequency increased in a dose-dependent way as the dose was titrated down. From these data the potency difference between the present drug inhaler combinations, Flixotide Diskus and Pulmicort Turbuhaler, was calculated to be between 1.50:1 (95% CI 1.10:1-2.05:1) and 1.75:1 (CI 1.26:1-2.43:1) depending on if patients with insufficient steroid-response were excluded from the calculations or not. In these steroid-naïve patients, the potency difference was evident only at low daily doses, below 200 mcg.", "Fluticasone propionate is a new inhaled corticosteroid with a 2:1 efficacy ratio compared with beclomethasone dipropionate with regard to lung function and symptom scores, without increased systemic activity. The aim of this study was to investigate whether this was also the case for bronchial hyperresponsiveness, assessed by both a direct (histamine) and an indirect (ultrasonically nebulised distilled water (UNDW)) provocation test.\n Fluticasone propionate, 750 micrograms/day, and beclomethasone dipropionate, 1500 micrograms/day, were compared in a randomised, double blind, crossover study consisting of two six week treatment periods, each preceded by a three week single blind placebo period. Twenty one non-smoking asthmatics (mean forced expiratory volume in one second (FEV1) 74.7% predicted, mean PC20histamine 0.36 mg/ml) completed the study.\n Fluticasone propionate and beclomethasone dipropionate improved FEV1, peak flow rates, asthma symptoms, and bronchial hyperresponsiveness to the same extent. Both fluticasone propionate and beclomethasone dipropionate caused an increase in PC20histamine (mean 2.29 [95% confidence interval 1.45 to 3.13] and 1.95 [1.07 to 2.84] doubling doses, respectively) and in PD20UNDW (1.12 [0.55 to 1.70] and 1.28 [0.88 to 1.70] doubling doses, respectively). Neither treatment changed morning serum cortisol levels, but fluticasone propionate decreased the number of peripheral blood eosinophils less than beclomethasone dipropionate, indicating smaller systemic effects of fluticasone propionate.\n These findings show that fluticasone propionate is as effective as twice the dose of beclomethasone dipropionate on bronchial hyperresponsiveness, assessed by provocation with both histamine and UNDW, without increased systemic activity.", "Treatment with inhaled steroids is an effective method of reducing bronchoconstriction and airway inflammation after allergen challenge. However, the duration of the protective effects of inhaled steroids after discontinuation of therapy has not been established.\n We sought to evaluate the protective effect of 1 week of inhaled steroid therapy against inhaled allergen challenge 12 hours after discontinuation of therapy.\n In this randomized, double-blind, placebo-controlled crossover trial, 26 asthmatic subjects (>18 years old) not using inhaled steroids were administered 200 microg of budesonide twice daily, 200 microg of fluticasone twice daily, or placebo twice daily for 1 week. Twelve hours after discontinuation of therapy, subjects were administered an inhaled allergen challenge. Each treatment period was separated by a 3-week washout period.\n When compared with placebo (26% +/- 14%), there was a slight but significant protection against the allergen-induced early response after fluticasone treatment (19% +/- 10%, P = .001) but not after budesonide treatment (23% +/- 13%, P = .08). However, when the area under the curve for the early airway response was examined, there was no difference between the 2 drugs in the amount of protection ( P = .62). Partial protection was demonstrated against the late-response allergen-induced sputum eosinophilia with both treatments ( P = .001). By contrast, no protection was observed against allergen-induced airway hyperresponsiveness for either treatment.\n The protective effects of inhaled steroids against allergen-induced early responses, airway eosinophilia, and allergen-induced airway hyperresponsiveness are partially or completely lost as early as 12 hours after discontinuation of therapy.", "The objective of this study was to assess the relative cost effectiveness of fluticasone via metered dose inhaler and budesonide via Turbuhaler((R)) in corticosteroid-naive patients with moderate asthma from a third-party payer perspective (German Sickness Funds).\n A retrospective economic assessment of direct medication costs of treatment was performed on data from a prospective, randomised, parallel group, 6-week clinical trial. 457 corticosteroid-naive patients between the ages of 18 and 70 years with moderate asthma were included in the intention-to-treat analysis.\n The fluticasone group had a higher proportion of successfully treated patients (those with a peak expiratory flow rate improvement of >/=10%) [47 vs 42%], a higher average proportion of symptom-free days (40 vs 34%) and lower direct healthcare costs [1997 Deutschmarks (DM)] per day (DM4.23 vs DM5.19) than the budesonide group. Therefore, the daily costs per successfully treated patient (DM9.00 vs DM12.36) and the cost per symptom-free day (DM10.58 vs DM15.26) were both lower with fluticasone than with budesonide. Sensitivity analysis demonstrated that these results were relatively robust over a wide range of plausible assumptions.\n These results showed that from the perspective of a third-party payer, fluticasone was more cost effective than budesonide over the 6-week study period.", "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.", "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.", "Chlorofluorocarbon-propelled metered dose inhalers are facing a worldwide ban. Dry powder inhalers have been developed for the agents used in treatment of asthma.\n Our objective was to compare the effects of two inhaled glucocorticosteroids in dry power inhalers: budesonide (delivered via Turbuhaler) and beclomethasone dipropionate (delivered via Rotahaler).\n A randomized, crossover study with two steroid-treatment periods of 8 weeks. At the end of the study, the treatment with the inhaled steroid was stopped for 4 weeks. Sixteen adult patients with moderately severe asthma participated. Before the study all patients were treated with an inhaled steroid in a median dose of 0.60 mg/day (range 0.15-0.80); during the study they received 0.20 mg twice daily. Peak expiratory flow rate was measured twice daily at home throughout the study, lung function was assessed every fourth week and airway responsiveness was measured before and after each period. Preference concerning efficacy and inhaler type was assessed at the end of the study.\n Twelve patients completed the study. Lung function, airway responsiveness, and symptoms deteriorated significantly in the steroid-free washout period; this period had to be shortened in 5/12 patients. Mean morning peak expiratory flow was significantly higher during budesonide treatment than during beclomethasone dipropionate treatment, the difference being 17 L/min (95% C.I.: 2-32 L/min, P = .026). Airway responsiveness improved 1.1 doubling concentrations after budesonide treatment, but decreased 0.3 doubling concentrations after beclomethasone dipropionate treatment. The difference between the values after budesonide and beclomethasone dipropionate treatment was 1.4 doubling concentrations (95% C.I.: 0.4-2.4 doubling concentrations, P = .033). Forced expiratory flow in one second improved slightly more during budesonide than during beclomethasone treatment. The difference was 4.3% predicted (95% C.I.: -0.7-9.3%). Most patients reported budesonide Turbuhaler to be more effective (10 versus 0) and easier to use (11 versus 1) than beclomethasone dipropionate Rotahaler.\n As a consequence of the difference in local potency of the steroids and the fact that Turbuhaler deposits more drug particles in the lung than Rotahaler, budesonide inhaled via Turbuhaler appeared to be a more effective steroid formulation than beclomethasone dipropionate inhaled via Rotahaler.", "Daily inhaled glucocorticoids are recommended for young children at risk for asthma exacerbations, as indicated by a positive value on the modified asthma predictive index (API) and an exacerbation in the preceding year, but concern remains about daily adherence and effects on growth. We compared daily therapy with intermittent therapy.\n We studied 278 children between the ages of 12 and 53 months who had positive values on the modified API, recurrent wheezing episodes, and at least one exacerbation in the previous year but a low degree of impairment. Children were randomly assigned to receive a budesonide inhalation suspension for 1 year as either an intermittent high-dose regimen (1 mg twice daily for 7 days, starting early during a predefined respiratory tract illness) or a daily low-dose regimen (0.5 mg nightly) with corresponding placebos. The primary outcome was the frequency of exacerbations requiring oral glucocorticoid therapy.\n The daily regimen of budesonide did not differ significantly from the intermittent regimen with respect to the frequency of exacerbations, with a rate per patient-year for the daily regimen of 0.97 (95% confidence interval [CI], 0.76 to 1.22) versus a rate of 0.95 (95% CI, 0.75 to 1.20) for the intermittent regimen (relative rate in the intermittent-regimen group, 0.99; 95% CI, 0.71 to 1.35; P=0.60). There were also no significant between-group differences in several other measures of asthma severity, including the time to the first exacerbation, or adverse events. The mean exposure to budesonide was 104 mg less with the intermittent regimen than with the daily regimen.\n A daily low-dose regimen of budesonide was not superior to an intermittent high-dose regimen in reducing asthma exacerbations. Daily administration led to greater exposure to the drug at 1 year. (Funded by the National Heart, Lung, and Blood Institute and others; MIST ClinicalTrials.gov number, NCT00675584.).", "The efficacy of budesonide (800 micrograms b.d.) and beclomethasone dipropionate (750 micrograms b.d.) in controlling the symptoms of asthma, pulmonary function, bronchial responsiveness to histamine, and adrenal function, was assessed in a double-blind, double-dummy cross-over study of 36 adult chronic asthmatic patients. The patients, the majority of whom were assessed to be affected to a severe degree, were insufficiently controlled in their current regimen of inhaled steroids and/or inhaled and oral bronchodilators. A 2 weeks baseline period preceded 6 weeks of treatment with each of the study drugs. Both treatment groups showed improvements from baseline in clinical assessment of lung function carried out after the first 6 weeks of treatment. No significant differences were seen throughout the entire 12 weeks study, when comparing the effects of the treatments on FEV1, FVC, PEF or the histamine PC20. Asthma severity, symptom score and inhaled bronchodilator use showed the same results after both treatments. It is concluded that inhalations of budesonide and beclomethasone dipropionate in high doses are equally potent in the treatment of severe asthma. There is no significant influence on the adrenal function and no significant side effects during a period equal to that of the present study.", "Twenty eight patients with chronic asthma took part in a double blind single crossover controlled trial of inhaled budesonide and inhaled beclomethasone dipropionate, using high doses of 1600 micrograms and 1500 micrograms daily respectively. Both drugs were administered by pressurised aerosol inhaler; the inhaler containing budesonide and its matching placebo were fitted with a collapsible spacer device. There was no significant difference in the control of asthma during the two six week treatment periods. There was no significant difference in FEV1 and forced vital capacity after four and six weeks of treatment or in mean morning and evening peak expiratory flow rates for the last 21 days of treatment. There was a small but statistically significant reduction in the daytime wheeze score while they were taking high dose budesonide but there was no difference for daytime activity, cough, and night symptoms. The mean basal cortisol concentrations were significantly lower after six weeks of high dose treatment than before treatment (budesonide p less than 0.01, beclomethasone p less than 0.05). There was no difference between mean basal cortisol values after six weeks of high dose treatment, and there was no effect on the rise of cortisol obtained after a short tetracosactrin test. High dose inhaled corticosteroids produced few side effects and were well tolerated.", "The efficacy and side-effects of a new corticosteroid, budesonide, was assessed by comparison with beclomethasone dipropionate in double-blind, cross-over study of 30 patients with chronic asthma. The treatment regimens were budesonide 200 micrograms twice daily by conventional pressurized aerosol with a tube spacer attached and beclomethasone 100 micrograms four times daily via a conventional inhaler. Each treatment was given for four weeks. Results were analyzed using Student's t-test for paired comparisons. No significant differences were found for morning and evening peak flow rates, symptom scores, bronchodilator inhaler usage or forced vital capacity. Forced expiratory volume in one second after 4 weeks on each treatment was significantly higher following budesonide therapy (p less than 0.05), but the absolute changes were small and unlikely to be of clinical relevance. There were no major side-effects during either treatment period, but compared with pre-treatment levels serum creatinine and lactic dehydrogenase levels rose significantly during treatment with budesonide (p less than 0.01 and p less than 0.05 respectively). None of these results reflected clinically important biochemical or haematological changes. There was a significant reduction in neutrophil counts following treatment with beclomethasone (p less than 0.05). In the short term treatment of chronic asthma, budesonide administered twice daily is as effective as four times daily beclomethasone. A twice daily dosage regimen should improve patient compliance with therapy.", "The efficacy and safety of Symbicort (budesonide and formoterol in a single inhaler) were compared with those of a high dose of the commonly used corticosteroid fluticasone propionate in patients with moderate persistent asthma.\n This randomized, double-blind, double-dummy, parallel-group study involved 373 patients with asthma (mean age 42 years; FEV(1) 78% of predicted; reversibility 21%). After a 2-week run-in period, during which patients received budesonide 200 microg twice daily, they were randomly assigned to treatment with either Symbicort Turbuhaler (budesonide/formoterol 160/4.5 microg, one inhalation twice daily) or Flovent/Flixotide Diskus (fluticasone propionate 250 microg twice daily) for 12 weeks.\n Significantly greater increases in morning PEF, the primary efficacy variable, were observed in patients treated with budesonide/formoterol compared with fluticasone propionate (27.4 L/min vs 7.7 L/min; p < 0.001). Evening PEF and clinic FEV(1) also favored budesonide/formoterol compared with fluticasone propionate (p < 0.001), as did use of reliever medication (p = 0.04) and the proportion of reliever-free days (p < 0.001). There were also numerical improvements in symptom-free days (60.4% vs 55.5%), night-time awakenings (7.9% vs 9.6%) and asthma-control days (57.8% vs 52.4%) in favor of budesonide/formoterol. The risk of an exacerbation was reduced by 32% in the budesonide/formoterol group compared with the fluticasone propionate group (p < 0.05). Both treatments were well tolerated.\n Symbicort (budesonide/formoterol in a single inhaler) was more effective than a high dose of fluticasone propionate in improving lung function, reducing use of reliever medication and improving control of moderate persistent asthma.", "Forty-five steroid-dependent asthmatic outpatients were treated twice daily for 51 weeks with a new inhalation steroid, budesonide (BUD), using a 750 ml spacer. During the initial 15 weeks the prednisone-sparing effects of a high daily dose (1600 micrograms) and a conventional dose (400 micrograms per day) were compared in a double-blind randomized trial including 50 patients. During the remaining 36 weeks 45 patients were treated openly with 1600 micrograms daily. All patients used other antiasthmatic drugs which were maintained throughout the study, except for inhalations of beta-2 agonists that could be used whenever needed. All patients but 2 were able to reduce the daily dose of oral prednisone. The mean daily dose decreased from 13.9 mg to 5.3 mg. Eighteen patients (40%) were able to discontinue oral prednisone. Adrenal gland function improved considerably as prednisone intake decreased. Oropharyngeal thrush frequency showed no change. No severe side effects were observed.", "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.", "Five hundred and eighty-five patients with moderate asthma, currently receiving 400-1000 micrograms day-1 of an inhaled corticosteroid, were treated for 6 weeks in a double-blind, randomized, parallel group study with either 500 micrograms day-1 fluticasone propionate as a dry powder via a Diskhaler inhaler, 500 micrograms day-1 fluticasone propionate via a pressurized inhaler or 1000 micrograms day-1 beclomethasone dipropionate via a pressurized inhaler. For all three treatment groups, mean morning and evening peak expiratory flow rates (PEFRs) increased within 1 week of the start of treatment. There were also improvements in clinic lung function, daytime and night-time asthma symptoms and a reduction in daytime and night-time rescue bronchodilator medication in all three groups. There were no statistically significant differences between the two formulations of fluticasone propionate in any of the efficacy parameters. Fluticasone propionate via the Diskhaler was significantly more effective than beclomethasone dipropionate over the 6 week study period in reducing diurnal variation (mean difference--4 l min-1, 95% CI--8 to 0 l min-1: P = 0.03). Fluticasone propionate via the Diskhaler produced a statistically significant improvement in night-time symptoms when compared to beclomethasone dipropionate whereas, beclomethasone dipropionate 1000 micrograms day-1 was statistically significantly more effective than both formulations of fluticasone propionate in improving daytime symptoms (P < 0.05). However, these statistical differences must be viewed together with the fact that very few patients recorded a score of 2 or more for both daytime or night-time symptoms. There was a similarly low incidence of adverse events with all three treatments with no evidence of hypothalamic pituitary adrenal (HPA)-axis suppression. The results of the 6-week comparative study showed that 500 micrograms day-1 fluticasone propionate whether administered via pressurized inhaler or Diskhaler is as effective and as safe as 1000 micrograms day-1 beclomethasone dipropionate administered via a pressurized inhaler in the treatment of moderate asthma. Over 12 months fluticasone propionate 500 micrograms day-1 via a pressurized inhaler was at least as effective and as well tolerated as beclomethasone dipropionate 1000 micrograms day-1.", "This study was designed to compare the efficacy and safety of a new inhaled corticosteroid, fluticasone propionate at a total daily dose of 200 micrograms, with beclomethasone dipropionate 400 micrograms/day in childhood asthma. A total of 398 asthmatic children (aged 4-19 years) were randomised to receive either fluticasone propionate 200 micrograms daily or beclomethasone dipropionate 400 micrograms daily for six weeks inhaled via a spacer device from a metered dose inhaler. During the study the patients recorded morning and evening peak expiratory flow rate (PEFR), symptom scores, and use of beta 2 agonist rescue medication. In addition, clinic visit PEFR and forced expiratory volume in one second were measured. Safety was assessed by recording all adverse events and by performing routine biochemistry and haematology screens including plasma cortisol concentration before and after treatment. For the purposes of analysis the diary card data were grouped into three periods: week 3 (days 15-21), week 6 (days 36-42), and weeks 1-6 (days 1-42). The results showed no significant difference between treatments on most efficacy parameters. However, there were significant differences in changes from baseline in favour of fluticasone propionate for % predicted morning PEFR both at week 3 (fluticasone propionate 6.1%, beclomethasone dipropionate 3.9%) and at week 6 (fluticasone propionate 8.3%, beclomethasone dipropionate 5. 9%) and % predicted evening PEFR at week 6 (fluticasone propionate 7.3%, beclomethasone dipropionate 4.9% and over weeks 1-6 (fluticasone propionate 5.5%, beclomethasone dipropionate 3.6%. Comparison between groups showed that the group receiving fluticasone propionate had a lower % of days with symptom-free exercise at week 6 (fluticasone propionate 87%, beclomethasone dipropionate 81%) and % days without rescue medication at week 6 (fluticasone propionate 87%, beclomethasone dipropionate 80%) and over weeks 1-6 (fluticasone propionate 80%, beclomethasone dipropionate 73%). Except for a higher incidence of sore throat in the fluticasone propionate group, the two treatments did not differ with regard to safety. There was no evidence of adrenal suppression with either treatment. In conclusion, fluticasone propionate 200 microgram daily ws at least as effective and as well tolerated as beclomethasone dipropionate 400 microgram daily in childhood asthma.", "New inhaled glucocorticosteroids and inhalers are being developed. Their clinical equipotency is difficult to assess and is often discussed.\n This study was carried out to compare the effect of budesonide Turbuhaler and fluticasone propionate (FP) Diskhaler in a dose reduction study in children (ages 5 to 16 years) with asthma.\n Children treated with budesonide administered through a pressurized metered-dose inhaler with a large volume spacer had their budesonide dose gradually reduced to define the minimal effective dose with this delivery system. After this period, 217 children were randomly allocated to treatment with half the dose of either budesonide Turbukaler or FP Diskhaler for 5 weeks in a double-blind trial. If no deterioration in asthma control was seen, the dose was further reduced by 50% at 5-week intervals until deterioration in asthma control was seen. Throughout the study, morning and evening peak expiratory flow, symptoms, and use of rescue beta 2-agonist were recorded in diaries. Lung function tests and a standardized exercise test were performed at the clinic at the end of each treatment period. Urine cortisol excretion (24 hours) was measured before and after the first 5-week treatment period. Standardized criteria for deterioration in asthma control, based on diary card variables and exercise testing, were used to determine the minimal effective dose for each patient; and from this, the number of dose reduction steps was calculated.\n No statistically significant difference was seen in number of dose reduction steps from baseline or in minimal effective dose between the two treatments; mean reduction was 1.59 dose steps for budesonide Turbuhaler and 1.65 dose steps for FP Diskhaler (p = 0.52), and minimal effective dose was 188 micrograms for budesonide Turbuhaler and 180 micrograms for FP Diskhaler. After these dose reductions, the same level of asthma control was observed in the budesonide Turbuhaler and FP Diskhaler groups. Furthermore, no statistically significant differences between the two inhaler-drug combinations were seen in daytime or nighttime symptoms, morning and evening peak expiratory flow, use of rescue beta 2-agonist, lung functions at the clinic, exercise-induced fall in lung function, or 24-hour urinary cortisol excretion during the first 5-week period.\n Microgram for microgram, budesonide Turbuhaler and FP Diskhaler are equally effective in treatment of children with moderate asthma.", "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.", "Qvar Autohaler efficacy on asthma control, assessed with E. Juniper asthma control questionnaire (ACQ), was compared with fluticasone and budesonide. An open randomized study, stratified (2:1) on the intake of long-acting beta2-mimetics (LAbeta2), was performed in patients with moderate to severe poorly controlled asthma (defined by at least one nocturnal discomfort in the last 5 days or a mean of 2 puffs of short-acting beta2-mimetics in the last 7 days or exercise dyspnea) despite treatment with beclomethasone < or = 1000 microg/day (or equivalent). 460 patients received Qvar Autohaler 800 microg/day (n = 149), fluticasone Diskus 1000 microg/day (n = 149) or budesonide Turbuhaler 1600 microg/day (n = 162) during 12 weeks. Asthma control improved in all groups, with no difference between groups. For patients treated with LAbeta2 (n = 286) a significantly greater improvement of the ACQ score was obtained with Qvar Autohaler versus fluticasone (1.0 +/- 1.0 vs. 0.6 +/- 0.9; P = 0.019), but not versus budesonide (0.9 +/- 0.9). Pulmonary function test improvements were similar in the 3 groups. The significant improvement in asthma control in patients receiving LAbeta2 suggests potential advantages for extrafine aerosols as part of anti-inflammatory treatment optimization.", "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.", "Fluticasone propionate, an inhaled corticosteroid with negligible systemic bioavailability via the oral route, is efficacious in the treatment of asthma when administered via metered-dose inhaler.\n To evaluate the efficacy and safety of inhaled fluticasone propionate powder in patients with moderate asthma previously treated with an inhaled corticosteroid.\n This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of 342 adolescent and adult patients with moderate asthma [forced expiratory volume in 1 second (FEV1) between 50% and 80% of predicted] treated previously by beclomethasone dipropionate or triamcinolone acetonide. Patients received fluticasone propionate powder 50 micrograms, 100 micrograms, 250 micrograms, or placebo via a breath-actuated inhalation device, the Diskhaler, twice daily for 12 weeks.\n Patients in the fluticasone propionate groups experienced a mean increase from baseline to endpoint in FEV1 ranging from 0.43 L to 0.47 L. Patients in the placebo group experienced a mean decrease from baseline of 0.22 L (P < .001). The probability of patients remaining in the study over time without developing signs of exacerbating asthma was significantly greater in the fluticasone propionate groups than in the placebo group (P = .001). Asthma symptom scores, supplemental rescue albuterol use, and number of nighttime awakenings due to asthma requiring treatment also improved significantly with all fluticasone propionate treatment regimens compared with placebo (P < .001). There were no statistically significant differences at endpoint among the three fluticasone propionate groups. No serious drug-related adverse events occurred.\n Fluticasone propionate powder (50, 100, and 250 micrograms) was well-tolerated and significantly improved lung function in patients with moderate asthma.", "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.", "The objective of this study was to compare the clinical effects of beclomethasone dipropionate (BDP) and budesonide in asthmatic children using two common ways of administration. Twenty-one children, aged 4-14 years, who regularly used inhaled corticosteroids for their control of asthma were included in the study. The drugs were studied by using a double-blind randomized cross-over design trial with a single-blind placebo period at the end. Each period lasted 3 weeks. The dosage was 100 micrograms b.i.d. for both drugs. Budesonide was administered via a spacer inhaler (Inhalet), and beclomethasone dipropionate via a standard actuator. Compared with placebo, both drugs significantly improved PEFR values for morning (20% for budesonide and 14% for BDP) and evening (14% for budesonide and 9% for BDP). Both morning and/or evening peak flows were significantly higher during the budesonide treatment as compared with the BDP treatment. In comparison with the placebo period, FEV1.0 was significantly improved with budesonide but not with BDP. Plasma cortisol, WBC counts, differential and eosinophilia counts in blood were determined at the beginning and the end of each period. All of the values except for the eosinophil counts were within normal ranges. Candida was looked for but not found in any case. No other adverse effects were registered. For most of the children, a deterioration of the state of their asthma and increased need for concomitant therapy during the placebo period confirmed their steroid dependence. The number of administrations with concomitant anti-asthmatic therapy increased during placebo by 61% as compared with the budesonide therapy, and by 40% compared with the BDP therapy.", "This study was undertaken to evaluate the efficacy and safety of fluticasone propionate, an inhaled corticosteroid, in adolescents and adults with moderate asthma who were previously taking inhaled corticosteroids. After a 2-week, open-label screening period, a double-masked, randomized, parallel-group, dose-ranging study was conducted over 12 weeks in 21 outpatient centers throughout the United States. Patients (N = 304) > or = 12 years of age with moderate asthma previously treated with inhaled corticosteroids and beta-sympathomimetic bronchodilators were enrolled. Patients were assigned to receive placebo or fluticasone propionate 100, 250, or 500 micrograms twice daily via a metered-dose inhaler without a spacer device. These doses refer to the amount of fluticasone propionate released from the valve of the metered-dose inhaler; the corresponding doses released from the activator of the metered-dose inhaler are 88 micrograms, 220 micrograms, and 440 micrograms, respectively. Between baseline and end point, mean values of forced expiratory volume in 1 second decreased 0.31 L in the placebo group and improved 0.39 L, 0.30 L, and 0.43 L in patients receiving 100-micrograms, 250-micrograms, and 500-micrograms fluticasone propionate, respectively. The differences between placebo and all treatment groups were statistically significant. More patients were withdrawn from placebo (72%) than from fluticasone propionate (13% to 16%) because of failure to meet predetermined asthma stability criteria. Differences in baseline-to-end point changes in morning peak expiratory flow rate, physician overall assessments and patient-rated assessment of symptoms, and albuterol use for symptom control also significantly favored each fluticasone propionate group over placebo. There were essentially no differences in efficacy among the three fluticasone propionate groups. Treatment-related adverse events occurred in 8% of placebo-treated patients and 13% to 15% of fluticasone propionate-treated patients; these events were mainly localized to the oropharynx/ larynx. A 12-week course of fluticasone propionate (100, 250, and 500 micrograms twice daily) was well tolerated and more effective than placebo based on maintenance of asthma stability, pulmonary function tests, physician and patient assessments, and rescue bronchodilator use. No dose-related effects were observed with the dosages of fluticasone propionate used in this study.", "There are no data currently available on the correct schedule for the initiation of treatment with nebulized suspension of budesonide in children with recurrent wheezing episodes. We compared the efficacy and safety of starting with a high dose followed by a stepwise decrease to a continuous low dose.\n In a double-blind design, 42 children aged 6 months to 3 years were randomly allocated to receive either a high starting dose of 1 mg budesonide twice daily followed by a stepwise decrease of 25% every second day for 1 week (group A) or a low dose of 0.25 mg twice daily for 1 week (group B). Efficacy was assessed with daily symptom scores and the systemic effect of the corticosteroids with the adrenocorticotropic hormone test.\n The two groups were comparable for all parameters evaluated. During the first week of treatment, there was a significant decrease in asthmatic symptomatology only in group A: a 59% decrease for wheezing (p = 0.0001), 39% for diurnal cough (p = 0.036), and 39% for nocturnal cough (p = 0.04). Mean time to clinical response was 3.0 days in group A and 5.7 days in group B (p = 0.02). This early improvement was sustained for the rest of the follow-up period. The high dose starting schedule was not associated with any change in serum cortisol level.\n The administration of nebulized suspension of budesonide at a high starting dose schedule followed by a rapid (1 week) stepwise decrease yields a significant early improvement in asthma symptoms and causes no change in serum cortisol levels.", "The response in asthmatic young children to inhaled steroids within the usual pediatric dose range is unknown. We therefore evaluated the dose-related response in young children with moderate asthma to inhaled fluticasone propionate (FP) (delivered via the Babyhaler spacer device) within the pediatric dose range. A total of 237 children (mean age 28 mo, range 12 to 47) with moderate asthmatic symptoms were studied in this multicenter, randomized, double-blind, parallel group, placebo-controlled study of 12 wk treatment following a 4-wk run-in period. The median use of rescue medication was 1 dose in 2 d during the run-in period. FP 50 micrograms twice daily (FP100) and 100 micrograms twice daily (FP200) was compared with placebo inhaled from a pressurized metered-dose inhaler (pMDI) and the Babyhaler spacer device. With FP200 there was a statistically significant improvement from baseline, as compared with the placebo group, in 8 of 10 diary card parameters, including the three symptom domains of wheeze, cough, and breathlessness, and use of rescue medication. FP100 produced a significant reduction in 5 of these 10 parameters, whereas no significant differences were found between the FP200 and FP100. The numbers of patients with at least one exacerbation during treatment with placebo, FP100, and FP200 were 37%, 26%, and 20%, respectively. This difference between placebo and FP200, as well as the dose-related order was significant (p < 0.05). Both FP doses were as well tolerated as placebo over the 12 wk treatment with a similar incidence of adverse effects. Asthmatic symptoms in 1- to 3-yr-old children responded in a significant and dose-related manner to treatment with FP within a pediatric dose range." ]	Fluticasone given at half the daily dose of beclomethasone or budesonide leads to small improvements in measures of airway calibre, but it appears to have a higher risk of causing sore throat and when given at the same daily dose leads to increased hoarseness. There are concerns about adrenal suppression with Fluticasone given to children at doses greater than 400 mcg/day, but the randomised trials included in this review did not provide sufficient data to address this issue.
CD004327	[ "2041443" ]	[ "Double-blind controlled study of botulinum toxin in adductor spasmodic dysphonia." ]	[ "The treatment of adductor spasmodic dysphonia using botulinum toxin A was conducted in 13 patients as a double-blind, placebo-controlled study. Patients were diagnosed independently by an interdisciplinary team consisting of speech pathologists, an otolaryngologist, and a neurologist. The toxin or saline was injected into each thyroarytenoid muscle under electromyographic and laryngoscopic guidance. Botulinum toxin A markedly reduced perturbation, decreased fundamental frequency range, and improved the spectrographic characteristics of the voice. Fundamental frequency and phonation time remained unchanged. Patients injected with botulinum toxin A noticed significant improvement in their voices in comparison with the placebo-treated group. Excessive breathiness of the voice occurred in two patients, and mild bleeding in one patient in the botulinum toxin A-treated group. Injection with saline resulted in edema of the vocal cord in one patient. Botulinum toxin A proved to be an effective and safe treatment of adductor spasmodic dysphonia." ]	The evidence from randomized controlled trials does not allow firm conclusions to be drawn about the effectiveness of botulinum toxin for all types of spasmodic dysphonia, or for patients with different behavioral or clinical characteristics.
CD006560	[ "18807252", "15385274", "9407576", "11298072", "12816022", "19843492" ]	[ "Combined intervention programme reduces inappropriate prescribing in elderly patients exposed to polypharmacy in primary care.", "An outreach geriatric medication advisory service in residential aged care: a randomised controlled trial of case conferencing.", "A randomized trial of geriatric liaison intervention in elderly medical inpatients.", "Outcomes of a randomized controlled trial of a clinical pharmacy intervention in 52 nursing homes.", "Improving primary care in rural Alabama with a pharmacy initiative.", "Analysis of the North Carolina long-term care polypharmacy initiative: a multiple-cohort approach using propensity-score matching for both evaluation and targeting." ]	[ "To evaluate the effect of a combined or a single educational intervention on the prescribing behaviour of general practitioners (GPs). The primary endpoint was effect on inappropriate prescribing according to the Medication Appropriateness Index (MAI).\n General practitioners were randomised to either (1) a combined intervention consisting of an interactive educational meeting plus feedback on participating patients' medication, (2) a single intervention with an interactive educational meeting or (3) a control group (no intervention). Elderly (>65 years) patients exposed to polypharmacy (>or=5 medications) were identified and approached for inclusion. Data on medications prescribed over a 3-month period were collected, and the GPs provided detailed information on their patients before and after the intervention. A pre- and post-MAI were scored for all medications.\n Of the 277 GPs invited to participate; 41 (14.8%) volunteered. Data were obtained from 166 patients before and after the intervention. Medication appropriateness improved in the combined intervention group but not in the single intervention group. The mean change in MAI and number of medications was -5 [95% confidence interval (CI) -7.3 to -2.6] and -1.03 (95% CI -1.7 to -0.30) in the combined intervention group compared with the group with the educational meeting only and the no intervention group.\n A combined intervention consisting of an interactive educational meeting plus recommendations given by clinical pharmacologists/pharmacists concerning specific patients can improve the appropriateness of prescribing among elderly patients exposed to polypharmacy. This study adds to the limited number of well-controlled, randomised studies on overall medication appropriateness among elderly patients in primary care. Important limitations to the study include variability in data provided by participating GPs and a low number of GPs volunteering for the study.", "efficient strategies are needed to provide specialist advice in nursing homes to ensure quality medical care. We describe a case conference intervention involving a multidisciplinary team of health professionals.\n to evaluate the impact of multidisciplinary case conferences on the appropriateness of medications and on patient behaviours in high-level residential aged care facilities.\n cluster-randomised controlled trial.\n ten high-level aged care facilities.\n 154 residents with medication problems and/or challenging behaviours were selected for case conference by residential care staff.\n two multidisciplinary case conferences involving the resident's general practitioner, a geriatrician, a pharmacist and residential care staff were held at the nursing home for each resident.\n outcomes were assessed at baseline and 3 months. The primary outcome was the Medication Appropriateness Index (MAI). The behaviour of each resident was assessed via the Nursing Home Behaviour Problem Scale.\n 45 residents died before follow-up. Medication appropriateness improved in the intervention group [MAI mean change 4.1, 95% confidence interval (CI) 2.1-6.1] compared with the control group (MAI mean change 0.4, 95% CI -0.4-1.2; P < 0.001). There was a significant reduction in the MAI for benzodiazepines (mean change control -0.38, 95% CI -1.02-0.27 versus intervention 0.73, 95% CI 0.16-1.30; P = 0.017). Resident behaviours were unchanged after the intervention and the improved medication appropriateness did not extend to other residents in the facility.\n multidisciplinary case conferences in nursing homes can improve care. Outreach specialist services can be delivered without direct patient contact and achieve improvements in prescribing.", "The aim of this study was to examine the effect of psychogeriatric intervention in a group of elderly medical inpatients over 75 years of age. In addition to usual care, intervention consisted of multidisciplinary joint treatment by a psychogeriatric team. The main purpose of intervention was to obtain the optimal level of physical functioning.\n In a prospective randomized trial the effect of the intervention (N = 140) compared with usual care (N = 97) was estimated for physical functioning, length of stay, and nursing home placement within 12 months of discharge.\n Substantially more patients assigned to the intervention group improved in their physical functioning, and fewer became worse. The mean length of stay was 5 days shorter for the intervention group. There were more readmissions to hospital in the usual care group (29.9%) compared with the intervention group (17.4%). Of the patients assigned to the intervention treatment, 18% were admitted to a nursing home. In the usual care group this was 27%. The effects of intervention remained statistically significant for all the outcome variables after controlling for possible confounding baseline characteristics.\n The intervention we studied had clinically relevant effects on important outcome variables. Psychiatric co-morbidity was an important risk factor for the outcome of the patients in our study. By combining elements from a psychiatric and geriatric consultation service with elements from a unit-driven service, we were able to improve health care for the elderly in our hospital in a feasible and cost-effective way.", "To evaluate whether a year long clinical pharmacy program involving development of professional relationships, nurse education on medication issues, and individualized medication reviews could change drug use, mortality and morbidity in nursing home residents.\n A cluster randomised controlled trial, where an intervention home was matched to three control homes, was used to examine the effect of the clinical pharmacy intervention on resident outcomes. The study involved 905 residents in 13 intervention nursing homes and 2325 residents in 39 control nursing homes in south-east Queensland and north-east New South Wales, Australia. The outcome measures were: continuous drug use data from government prescription subsidy claims, cross-sectional drug use data on prescribed and administered medications, deaths and morbidity indices (hospitalization rates, adverse events and disability indices).\n This intervention resulted in a reduction in drug use with no change in morbidity indices or survival. Differences in nursing home characteristics, as defined by cluster analysis with SUDAAN, negated intervention-related apparent significant improvements in survival. The use of benzodiazepines, nonsteroidal anti-inflammatory drugs, laxatives, histamine H2-receptor antagonists and antacids was significantly reduced in the intervention group, whereas the use of digoxin and diuretics remained similar to controls. Overall, drug use in the intervention group was reduced by 14.8% relative to the controls, equivalent to an annual prescription saving of A64 dollars per resident (approximately 25 pound sterling).\n This intervention improved nursing home resident outcomes related to changes in drug use and drug-related expenditure. The continuing divergence in both drug use and survival at the end of the study suggests that the difference would have been more significant in a larger and longer study, and even more so using additional instruments specific for measuring outcomes related to changes in drug use.", "The effect of pharmaceutical care on the prevention, detection, and resolution of medication-related problems in high-risk patients in a rural community was studied. Adult patients who received care at clinics in a medically underserved area of Alabama and who were identified as being at high risk of medication-related adverse events were randomly assigned to a control group or an intervention group. The control group received standard medical care, and the intervention group received pharmaceutical care, including a medical record review, a medication history review, pharmacotherapeutic evaluation, and patient medication education and monitoring over a one-year period. A total of 69 patients completed the study (33 in the intervention group and 36 in the control group). The percentage of patients responding to hypertension, diabetes, dyslipidemia, and anticoagulation therapy increased significantly in the intervention group and declined in the control group. Ratings for inappropriate prescribing improved in all 10 domains evaluated in the intervention group but worsened in 5 domains in the control group. There were no significant differences between the groups at 12 months in health-related quality of life or medication misadventures. Medication compliance scores improved in the intervention group but not in the control group. Medication knowledge increased in the intervention group and decreased in the control group. Pharmaceutical care in a rural, community-based setting appeared to reduce inappropriate prescribing, enhance disease management, and improve medication compliance and knowledge without adversely affecting health-related quality of life.", "The high cost and undesirable consequences of polypharmacy are well-recognized problems among elderly long-term care (LTC) residents. Despite the implementation of the 1987 Omnibus Budget Reconciliation Act, which requires pharmacist review of drug regimens in this setting, medical and drug costs for LTC residents have continued to increase.\n This study evaluates the North Carolina Long-Term Care Polypharmacy Initiative, a large-scale medication therapy management program (MTMP) that combined drug utilization review activities with drug regimen review techniques.\n This was a prospective records-based study that used a difference-in-difference model with both historical and nonintervention group controls. To ensure equivalence among subjects, propensity scoring was used to match study subjects from participating LTC facilities with comparison subjects from nonparticipating facilities. Residents with interventions were grouped for analysis by intervention type-retrospective only, prospective only, or dual type (residents with both prospective and retrospective interventions)-and by intervention stage-review, recommendation, and drug change-plus an all-inclusive \"all types\" grouping that aggregated groups by intervention type, for a total of 10 total cohorts.\n In the overall population of 5255 study subjects identified, a US $21.63 per member per month drug-cost savings was observed. Although only 1 of 10 cohorts had a change in the number of drug fills, substantial reductions in 2 of 5 types of drug alerts were observed in all 10 cohorts. A reduction in the relative risk for hospitalization (0.84 [95% CI, 0.71-1.00]) was observed in the cohort of residents receiving a retrospective review.\n This Initiative suggests that an MTMP can be quickly launched in a large number of LTC facility residents to produce monetary drug-cost savings and improved health outcomes. Additionally, the evaluation of this program illustrates the utility of using propensity scoring techniques to target future intervention groups in a cost-effective manner." ]	This review highlights the paucity of research into interventions to improve outcomes for multimorbidity with the focus to date being on co-morbid conditions or multimorbidity in older patients. The limited results suggest that interventions to date have had mixed effects but have shown a tendency to improve prescribing and medication adherence, particularly if interventions can be targeted at risk factors or specific functional difficulties in people with co-morbid conditions or multimorbidity. There is a need for clear definitions of participants, consideration of appropriate outcomes, and further pragmatic studies based in primary care settings.
CD001285	[ "9033441", "18415831", "11908511", "9227720", "8103655", "11956046", "12890374", "1978947", "2844548", "8104272", "11368732", "8296255", "18186995", "6958474", "15978535", "8703248", "12410322", "7582281", "9887897", "9438143", "17312651", "16850457", "8970342", "10335000", "9850359", "1357550", "1357551", "7439516", "12113382", "9864004", "9864001", "9626025", "2669554", "14533658", "20446755", "338009", "18266402", "8036292" ]	[ "Short-term regular beta 2-adrenergic agonists treatment is safe in mild asthmatics taking low doses of inhaled steroids.", "Effect of feedback letters to physicians and pharmacists on the appropriate use of medication in the treatment of asthma.", "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.", "Effects of the long acting beta agonist formoterol on asthma control in asthmatic patients using inhaled corticosteroids. The Netherlands and Canadian Formoterol Study Investigators.", "Asthma control during and after cessation of regular beta 2-agonist treatment.", "Beta2-agonist tolerance and exercise-induced bronchospasm.", "Inhaling beta(2)-agonist with heliox-driven in bronchial asthma.", "Use of inhaled corticosteroids in patients with mild asthma.", "Effects of inhaled beclomethasone dipropionate on beta 2-receptor function in the airways and adrenal responsiveness in bronchial asthma.", "Regular inhaled salbutamol and airway responsiveness to allergen.", "Long-acting beta2-agonist monotherapy vs continued therapy with inhaled corticosteroids in patients with persistent asthma: a randomized controlled trial.", "Changes in methacholine induced bronchoconstriction with the long acting beta 2 agonist salmeterol in mild to moderate asthmatic patients.", "Poor adherence with inhaled corticosteroids for asthma: can using a single inhaler containing budesonide and formoterol help?", "Methodological aspects on clinical trials with inhaled corticosteroids: results of two comparisons between two steroid aerosols in patients with asthma.", "Inhaled beta-agonists improve lung function but not maximal exercise capacity in cystic fibrosis.", "Effect of inhaled corticosteroids on bronchial hyperresponsiveness in patients with mild asthma.", "The relationship among inspiratory muscle strength, the perception of dyspnea and inhaled beta2-agonist use in patients with asthma.", "Interaction of inhaled beta 2 agonist and inhaled corticosteroid on airway responsiveness to allergen and methacholine.", "Buteyko breathing techniques in asthma: a blinded randomised controlled trial.", "Long-term effects of formoterol and salbutamol on bronchial hyperreactivity and beta-adrenoceptor density on lymphocytes in children with bronchial asthma.", "Management of acute asthma in children using metered dose inhaler and small volume nebulizer.", "Exhaled nitric oxide in the management of childhood asthma: a prospective 6-months study.", "An inhaled glucocorticoid does not prevent tolerance to the bronchoprotective effect of a long-acting inhaled beta 2-agonist.", "Randomised trial of an inhaled beta2 agonist, inhaled corticosteroid and their combination in the treatment of asthma.", "Efficacy of chlorofluorocarbon-free beclomethasone dipropionate 400 micrograms day-1 delivered as an extrafine aerosol in adults with moderate asthma.", "Long-term effects of a long-acting beta 2-adrenoceptor agonist, salmeterol, on airway hyperresponsiveness in patients with mild asthma.", "Tolerance to the nonbronchodilator effects of inhaled beta 2-agonists in asthma.", "A comparative trial of slow-release aminophylline, salbutamol and a half dose combination in the prevention of childhood asthma.", "Comparison of second controller medications in addition to inhaled corticosteroid in patients with moderate asthma.", "Clinical efficacy of low-dose inhaled budesonide once or twice daily in children with mild asthma not previously treated with steroids.", "An inhaled steroid improves markers of airway inflammation in patients with mild asthma.", "Effects of treatment with formoterol on bronchoprotection against methacholine.", "Comparison of dose-response effects of inhaled beclomethasone dipropionate and budesonide in the management of asthma.", "Efficacy and safety of fluticasone propionate 44 microg/salmeterol 21 microg administered in a hydrofluoroalkane metered-dose inhaler as an initial asthma maintenance treatment.", "Cost effectiveness of leukotriene receptor antagonists versus long-acting beta-2 agonists as add-on therapy to inhaled corticosteroids for asthma: a pragmatic trial.", "Betamethasone valerate inhalation and exercise-induced asthma in adults.", "Salmeterol/fluticasone propionate via Diskus once daily versus fluticasone propionate twice daily in patients with mild asthma not previously receiving maintenance corticosteroids.", "Pulmicort Turbohaler once daily as initial prophylactic therapy for asthma." ]	[ "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.", "Suboptimal medication treatment of asthma has been reported. More specifically, short-acting beta 2-agonists are overused, while inhaled corticosteroids are underused. This can be related in part to poor adherence by patients to the prescribed regimen and to professionals' failure to comply with practice guidelines. Feedback seems to have an effect on professional practices related to medication use.\n To assess the impact of feedback letters to physicians and pharmacists on their patients' appropriate use of asthma medication.\n Two randomized trials were set up in the province of Quebec, Canada: one with physicians and another with pharmacists. A sample of voluntary physicians and pharmacists was randomly assigned to either the experimental group or to the control group. Those in the experimental groups received three consecutive feedback letters over a 9-month period summarizing the asthma medications acquired by their patients over the preceding year. The feedback focused on short-acting beta 2-agonists, long-acting beta 2-agonists and antileukotrienes and provided information on compliance with five appropriate-use criteria. Pharmacists received aggregate profiles and individual profiles with patients' names, while most physicians received aggregate profiles for all their eligible patients. Each mailing also included a pamphlet that summarized practice guidelines on asthma treatment.\n Seventy-one physicians and 60 pharmacists participated in the study. Physicians who received the feedback letters did not differ from those in the control group in terms of their proportion of prescriptions compliant with the criteria, either before the feedback or after it (p > 0.05). The before-after difference was also similar between groups. The same was true for pharmacists. However, although the before-after difference for criteria 1 (frequency of use of short-acting beta 2-agonists) and 2 (frequency of use of long-acting beta 2-agonists) did not reach the usual statistical significance threshold of 0.05, the p value was under 0.10.\n As designed in this study, feedback provided to physicians did not improve the appropriate use of asthma medication. However, feedback to pharmacists is promising, especially when including patients' names so that pharmacists can intervene more specifically.", "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 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.", "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)", "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.", "To evaluate the effectiveness of a helium-oxygen mixture (79%He- 21%O(2)) as an aerosolizing compressed gas for beta(2)-agonist therapy in patients with an asthma exacerbation.\n Twenty-four patients in the outpatient department with a mild to moderate exacerbation of asthma were enrolled. The patients were randomly divided into an experimental group (13 cases) and a control group (11 cases). The experimental group inhaled Berotec with heliox-driven, and the control group inhaled Berotec with compressed air-driven. Eight hospitalized patients in the respiratory department with severe exacerbation of asthma were enrolled. The patients inhaled Berotec with heliox-driven or compressed air-driven in a random order.\n The results of spirometric parameters and arterial blood-gas analysis were measured. In the mild to moderate asthma patients, no statistical differences between the two groups for forced vital capacity (FVC), forced expired volume in one second (FEV(1)), and expiratory flow in 50% forced vital capacity (FEF(50)) were presented. But the severe patients showed significant differences between heliox-driven and compressed air-driven for FVC, FEV(1), FEF(50) and partial pressure of oxygen (PaO(2)).\n Compared with the traditional inhalation of beta(2)-agonist therapy using compressed air-driven, the method of inhaling beta(2)-agonist with heliox-driven has more obvious benefits for those suffering from severe asthma. This is likely due to the cooperative effects between inhaling heliox on its physical gas properties and improving delivery of beta(2)-agonist in the treatment of exacerbation of severe asthma.", "A double blind, parallel group study was carried out to investigate the effect of inhaled budesonide in a moderate (200 micrograms) and a low (100 micrograms) twice daily dosage compared with the effect of placebo in 103 adults with mild symptomatic asthma. Subjects recorded peak expiratory flow (PEF), asthma symptoms, and beta 2 agonist consumption at home for a period of seven weeks (a one week run in and six weeks' treatment). Morning baseline PEF (around 80% of predicted normal) increased non-significantly to 88% with 200 micrograms budesonide daily and to 90% (p less than 0.05) with 400 micrograms, compared with 81% with placebo. Evening PEF (around 94% of predicted normal) did not change significantly with active or placebo treatment. By comparison with placebo, there was a significant decrease in nocturnal asthma symptoms and beta 2 agonist consumption. The changes during the day were less pronounced and significant only for 400 micrograms budesonide daily. No significant differences between the two active treatments were detected. It is concluded that low doses of inhaled budesonide are effective in patients with mild symptomatic asthma, particularly for night time symptoms and early morning lung function. The early introduction of inhaled corticosteroids for patients with mild asthma and night time symptoms may improve their quality of life during the night and early morning.", "Sixteen patients suffering from bronchial asthma, with or without chronic bronchitis, sufficiently severe to be treated with inhaled corticosteroids, were studied in a single-blind trial (blind observer) of beclomethasone dipropionate (BDP) given in three randomized dosage regimens: 500, 1000 and 2000 micrograms per day, each for 4 weeks. The beta 2-adrenergic agonist response curve showed a dose-dependent increase in FEV1 which was not affected by different doses of BDP. A small but significant reduction in basal cortisol levels was observed after BDP 500 micrograms/day. There was no significant difference between the various doses of BDP in reducing cortisol level and stimulation with tetracosactide remained unchanged. The study showed a gradual, dose-dependent improvement in lung function, statistically significant for morning peak expiratory flow rate at BDP 2000 micrograms/day. Dyspnoea score and beta 2-agonist use decreased, reflecting the anti-asthmatic effects. An increase in total leukocyte count was observed, together with a decrease in the eosinophil count. Oral candidiasis was seen in 2 out of 16 patients. It is concluded that the clinical anti-asthmatic effects of corticosteroid treatment by inhalation are not due to modulation of beta 2-receptor function in the airways.", "Regular inhaled beta 2 agonist causes tolerance to the acute protective effect of beta 2 agonist against bronchoconstriction induced by chemical stimuli such as AMP, histamine, and methacholine. We examined a more clinically relevant stimulus, inhaled allergen, in a double-blind, cross-over, random-order trial in 13 mild atopic asthmatics, who had not used beta 2 agonist for at least 4 weeks. We compared regular inhaled salbutamol (200 micrograms four times daily for 2 weeks) with placebo (2 weeks) for effects on bronchodilator response, baseline methacholine, and allergen airway responsiveness, and on the acute protective effect of salbutamol against both stimuli. Baseline forced expiratory volume in 1 s (FEV1), bronchodilator response, and methacholine responsiveness were the same during both treatment periods. After regular salbutamol, the allergen PC20 (provocation concentration producing a 20% FEV1 decrease) fell by 0.91 (SD 0.66) (p = 0.0009) doubling doses, and the protective effects of salbutamol on methacholine and allergen were both significantly reduced (p = 0.026 and 0.025, respectively). Taking into account the reduced baseline allergen PC20, the post-salbutamol allergen PC20 was almost 2 doubling doses (1.94 [1.43], p < 0.01) lower during salbutamol treatment. Thus, 2 weeks of regular inhaled salbutamol increased airway responsiveness to allergen but not to methacholine, and caused tolerance to the protective effect of salbutamol on bronchoconstriction induced by both stimuli. These effects of inhaled beta 2 agonist provide further evidence to support detrimental effects of their regular use.", "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.", "Beta-2 agonists protect against non-specific bronchoconstricting agents such as methacholine, but it has been suggested that the protection afforded by long acting beta 2 agonists wanes rapidly with regular treatment.\n The changes in airway responsiveness were investigated during and after eight weeks of regular treatment with salmeterol 50 micrograms twice daily in 26 adult asthmatic patients, 19 of whom were receiving maintenance inhaled corticosteroids. The study was of a randomised, placebo controlled, double blind design. Airway responsiveness to methacholine was measured as PD20 by a standardised dosimeter technique 12 hours after the first dose, at four weeks and eight weeks during treatment (12 hours after the last dose of test medication), and at 60 hours, one week and two weeks after stopping treatment.\n There were no significant differences between the baseline characteristics of the two groups. A significant improvement in PD20 was seen at all points during treatment with salmeterol compared with the placebo group, with no significant fall off with time. PD20 measurements returned to baseline values after cessation of treatment with no significant difference from the placebo group.\n Salmeterol gave significant protection against methacholine induced bronchoconstriction 12 hours after administration. This protection was of small magnitude, but there was no significant attenuation with eight weeks of regular use and no rebound increase in airway responsiveness on stopping treatment in a group of moderate asthmatic patients, the majority of whom were receiving inhaled corticosteroids.", "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.", "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.", "To investigate the effects of inhaled beta-agonists on sub-maximal and maximal exercise capacity, breathing pattern, dyspnoea, leg-discomfort and spirometry in patients with cystic fibrosis (CF).\n Eight patients performed two maximal incremental cycle-ergometry tests on separate days with inhaled placebo or salbutamol (600 microg) administered before each test in a randomized, double-blind, placebo-controlled crossover trial. Primary outcomes were exercise duration (Exdur) in seconds (s) and maximal oxygen uptake (VO2max) in litres/minute (L/min). Forced expiratory volume in 1 s (FEV1) was measured immediately pre-inhaler, post-inhaler and post-exercise. Dyspnoea and leg-discomfort were assessed post-exercise.\n Within-day FEV1 comparisons demonstrated that the placebo test day FEV1 improved significantly post-exercise (0.11 L, p<0.05) and the salbutamol test day FEV1 improved significantly post-inhaler (0.22 L, p<0.001) and post-exercise (0.07 L, p<0.01). Between-day FEV1 comparisons demonstrated significant improvements in post-inhaler (0.17 L, p<0.05) and post-exercise (0.13 L, p<0.05) FEV1 following salbutamol. Sub-maximal and maximal exercise showed no significant difference as shown by Exdur (547+/-154 s vs. 529+/-127 s) and VO2max (1.9+/-0.5 L/min vs. 1.9+/-0.6 L/min). No significant change in breathing pattern, dyspnoea or leg-discomfort was detected. The study had a power of 92% to detect a 10% improvement in Exdur.\n In adults with CF, salbutamol improves post-exercise FEV1 and is safe when administered immediately before exercise but does not improve exercise capacity, exercise-induced dyspnoea or leg-discomfort.", "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.", "It is well documented that the perception of dyspnea (POD), subjectively reported by patients, is related to the activity and strength of the inspiratory muscles, and influences the use of 'as needed' beta2-agonists.\n To investigate the relationship among the increase in inspiratory muscle strength after specific inspiratory muscle training, beta2-agonist consumption and the POD in patients with persistent, mild to moderate asthma.\n Inspiratory muscle strength, daily beta2-agonist consumption and the POD were measured in 30 patients with mild to moderate asthma. Patients were then randomly assigned to two groups: one group received specific inspiratory muscle training until an increase of more than 20 cm H2O was reached, and one group was a control group and received sham training. Inspiratory muscle strength, the POD and daily beta2-agonist consumption were assessed during and after the training period.\n There was no good correlation between the baseline maximal inspiratory pressure and the POD, or between the baseline maximal inspiratory pressure and the mean daily beta2-agonist consumption. However, there was a significant correlation between the POD and the mean daily beta2-agonist consumption. The increase in inspiratory muscle strength after the inspiratory muscle training was closely correlated with the decrease in the POD (P<0.001) and the decrease in beta2-agonist consumption (P<0.001).\n The present study shows that, in patients with mild to moderate, persistent asthma, there is a correlation between the POD and the mean daily beta2-agonist consumption. When the inspiratory muscles are strengthened, there is a significant decrease in the POD and in beta2-agonist consumption.", "Regular treatment with salbutamol increases airway responsiveness to allergen but not to methacholine and produces tolerance to the bronchoprotective effect of salbutamol. The current study addresses the effect of inhaled corticosteroid on these aspects of regular beta 2 agonist use. A group of 13 atopic asthmatic subjects free from all asthma medications and remote from allergen exposure were studied. We used a double-blind, random-order, crossover study to compare four 1-wk treatment periods with > or = 1 wk washout: placebo, salbutamol, 200 micrograms four times per day, budesonide, 400 micrograms four times per day, and the combination of salbutamol and budesonide. We measured the methacholine PC20 and the methacholine dose shift produced acutely by 200 micrograms salbutamol after 7 d and the allergen PC15 after 8 d treatment. Blinded medications were withheld for 8 to 10 h before measurements. The methacholine PC20 was not affected by regular salbutamol but increased significantly (p < 0.014) after both budesonide-containing regimens. Neither the dose shift nor its significant reduction by regularly used beta 2 agonist were influenced by the inhaled corticosteroid. The four allergen PC15 values were significantly different from each other. Compared with placebo, the allergen PC15 was 0.6 doubling doses lower after salbutamol (p = 0.021) and 1.3 doubling doses higher after budesonide (p < 0.001); the allergen PC15 was reduced by 0.53 doubling doses from this new baseline (p = 0.039) when salbutamol and budesonide were used together.(ABSTRACT TRUNCATED AT 250 WORDS)", "To evaluate the effect of Buteyko breathing techniques (BBT) in the management of asthma.\n Prospective, blinded, randomised study comparing the effect of BBT with control classes in 39 subjects with asthma. The study was conducted from January 1995 to April 1995.\n Subjects recruited from the community, aged 12 to 70 years, with asthma and substantial medication use.\n Medication use; morning peak expiratory flow (PEF); forced expiratory volume in one second (FEV1); end-tidal (ET) CO2; resting minute volume (MV); and quality of life (QOL) score, measured at three months.\n No change in daily PEF or FEV1 was noted in either group. At three months, the BBT group had a median reduction in daily beta 2-agonist dose of 904 micrograms (range, 29 micrograms to 3129 micrograms), whereas the control group had a median reduction of 57 micrograms (range, -2343 micrograms to 1143 micrograms) (P = 0.002). Daily inhaled steroid dose fell 49% (range, -100% to 150%) for the BBT group and 0 (range, -82% to +100%) for the control group (P = 0.06). A trend towards greater improvement in QOL score was noted for BBT subjects (P = 0.09). Initial MV was high and similar in both groups; by three months, MV was lower in the BBT group than in the control group (P = 0.004). ET CO2 was low in both groups and did not change with treatment.\n Those practising BBT reduced hyperventilation and their use of beta 2-agonists. A trend toward reduced inhaled steroid use and better quality of life was observed in these patients without objective changes in measures of airway calibre.", "Long-term treatment with short-acting beta 2-sympathomimetic drugs has recently been suggested to be due to a rise in asthma mortality. This effect has been attributed to an increase in bronchial hyperreactivity, a desensitization of beta 2-adrenoceptors and/or a rebound effect after cessation of the therapy. Formoterol, a new long-acting beta 2-symathomimetic drug, has been reported to possess not only bronchodilatation but also antiinflammatory effects. The aim of the present study was to investigate whether long-term effects of salbutamol and/or formoterol could deteriorate asthma management. Therefore, in a trial lasting 90 days, we evaluated the effects of the two drugs on lung function, on the protection they provided against inhalative provocation with histamine, and on tachyphylaxis as monitored by the beta-adrenergic density on mononuclear leukocytes (MNL). Two groups of 11 children each with stable asthma were treated with daily doses of either 4 x 200 micrograms salbutamol or 2 x 24 micrograms formoterol in monotherapy. The lung function was measured six times during the trial period, on day 1, and on day 90, before and after inhaling the drug and at all investigations both with and without histamine provocation. In both groups, the bronchodilatory effect of either formoterol or salbutamol remained constant. The lung function values before and after drug inhalation (specific airway resistance sRAW, forced expiration volume FEV1, vital capacity VC) did not alter significantly. After histamine provocation, the protection was more pronounced in the formoterol group. No changes in the beta-adrenoceptor density on MNL and no significant side effects were seen throughout the trial period. We therefore conclude that formoterol protects significantly better against the bronchial challenge with histamine than does salbutamol. Both drugs did not deteriorate the lung function in asthmatic children. In addition, there was no evidence that long-term treatment leads to a desensitization of beta 2-sympathomimetic effects.", "To determine whether the administration of beta2-agonist by Metered Dose inhaler (MDI) with accessory device (AD) is a as effective as the administration of beta2-agonist by small volume nebulizers (SVN) for the treatment of acute asthma.\n A cross sectional study was conducted at Emergency Room (ER) of National Institute of Child Health (NICH), Karachi, between October 2000 to March 2001. This study included 150 children, 6 months and older with a history of wheeze and presenting with an acute asthma exacerbation. Children were categorized into mild, moderate and severe asthma according to medical scoring system. Children were assigned randomly into group A and B to receive standard dose of beta2-agonist (salbutamol) by MDI/AD (group A) or SVN (group B). Baseline characteristics and asthma severity were recorded. All variables (dyspnoea, use of accessory muscles, cyanosis, respiratory rate, heart rate, blood pressure, oxygen saturation, pulsus paradoxus, and wheeze) and Peak Expiratory Flow Rate (PEFR) in children 5 years and older, were determined at pre and post inhalation therapy.\n Both groups did not differ in demographic characteristics. There were no significant differences in outcome measures. In children treated with MDI/ADs and SVNs. PEFR increased significantly in both the groups after completion of treatment, but PEFR was not statistically significant when compared in between groups.\n The data suggested that MDI/AD is an effective alternative to nebulizer for the treatment of children with acute asthma exacerbation in the ER.", "Fractional exhaled nitric oxide (FeNO) is elevated in asthma and reflects eosinophilic airway inflammation. The aim of this prospective, randomized, single-blind study was to examine whether the inclusion of repeated FeNO measurements into asthma monitoring leads to an improvement in asthma outcome. Forty-seven children with mild to moderate asthma were allocated to a FeNO group (n = 22) and to a control group (n = 25). In the FeNO group therapy was based on symptoms, beta-agonist use, lung function, and FeNO whereas in the control group therapy was based on symptoms, beta-agonist use and lung function only. Patients performed five visits in 6 weeks intervals. Frequency of respiratory symptoms, beta-agonist use, FEV(1)% predicted and the frequency of exacerbations were similar between groups. Patients in the FeNO group received higher doses of inhaled corticosteroids (ICS) (control group: median (interquartile range): 241 microg (26-607 microg); FeNo group: 316 microg (200-500 microg) and had significantly higher MEF(50)% predicted (control group: median (interquartile range): 68.5% (55.8-83.1%); FeNO group: 83.2% (62.9%-98.3%). At a cut-off point of 22.9 ppb FeNO the best predictive value for exacerbations with a sensitivity of 80% and specificity of 60% was found. Significant relationships were observed between FeNO and dose of ICS (beta = -8.77; P < 0.002), beta-agonist use 2 weeks prior to a visit (beta = 0.11; P < 0.05), asthma symptoms (beta = 0.02; P < 0.0001), and bronchial hyperresponsiveness (beta = 0.04; P = 0.02). In conclusion, FeNO was related to important markers of asthma control. A therapy regimen aimed at lowering FeNO in children with asthma improved parameters of small airway function, but was not able to improve clinical markers of asthma control.", "There is increasing evidence for the development of tolerance to the protective effects of inhaled beta 2-agonists against bronchoconstrictor stimuli. Animal studies have suggested that glucocorticoids protect against the down-regulation of beta 2-receptors after chronic exposure to beta 2-agonists. In a double-blind placebo-controlled crossover study in 12 patients with mild asthma, we investigated the effect of inhaled budesonide or identical placebo on the protection conferred by albuterol (200 micrograms) against methacholine-induced bronchoconstriction before and after treatment with the long-acting beta 2-agonist salmeterol. Patients were randomized to be treated for 3 wk with inhaled budesonide (800 micrograms twice a day) or placebo; salmeterol (50 micrograms twice a day) was added during the third week. Airway responsiveness to methacholine was measured 15 min after albuterol, both before and exactly 12 h [corrected] after the last salmeterol dose. Mean FEV1 increased significantly after 2 wk of budesonide (p < 0.05) and increased further after salmeterol (p < 0.05) compared with placebo. After 2 wk, the bronchoprotective effect of albuterol against methacholine was significantly greater with budesonide than with placebo (3.4 versus 2.4 doubling dilutions; p < 0.05), consistent with an improvement in airway hyperresponsiveness with budesonide therapy. However, regular salmeterol treatment for 1 wk significantly diminished the protection conferred by albuterol against methacholine challenge, both with budesonide and with placebo (-1.1 +/- 0.42 and -1.41 +/- 0.30 doubling dilutions, respectively). There was no significant difference in the loss of bronchoprotection seen with salmeterol between budesonide and placebo treatment periods. Our study suggests that even a high dose of an inhaled glucocorticoid fails to prevent the loss of bronchoprotection produced by regular beta 2-agonist therapy.", "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.", "Beclomethasone dipropionate (BDP) has been reformulated in a chlorofluorocarbon-free propellant, hydrofluoroalkane-134a (HFA), resulting in an extrafine aerosol which gives improved drug delivery to the airways. The objective of this 6 week, placebo-controlled study was to evaluate the clinical efficacy of HFA-BDP 400 micrograms day-1 in 256 adult patients with moderate asthma. This is a lower daily dose than that recommended for existing BDP inhalers in current treatment guidelines for moderate asthma (NIH publication 95-3659). Another objective was to evaluate whether delivering the 400 micrograms dose as four actuations of 50 micrograms twice daily (HFA-BDP 50 micrograms) provided equivalent asthma control to delivering the dose as two actuations of 100 micrograms twice daily (HFA-BDP 100 micrograms) without the use of a spacer or holding chamber. Both active treatments produced a significant change from baseline in morning peak expiratory flow (PEF), which was significantly larger than that in the placebo group (P < or = 0.017) throughout the study. The mean changes from baseline in morning PEF at weeks 5-6 were 47.0 l min-1 in the combined HFA-BDP group and 16.5 l min-1 in the HFA-placebo group. The two dose strengths were statistically equivalent (P = 0.017 for equivalence testing). The active treatments also produced significant improvements compared with placebo in evening PEF, forced expiratory volume in the first second, forced expiratory flow over 25-75% of vital capacity, sleep disturbance scores and daily beta-agonist use. The study medication was well tolerated, with a low incidence of adverse events. The results from this study demonstrate that a daily dose of 400 micrograms HFA-BDP (given in 50 micrograms and 100 micrograms strengths) provides dose proportionality and effective control in patients with moderate asthma.", "Asthma is characterized by hyperresponsiveness of the airways to bronchoconstrictive stimuli. Long-acting beta 2-adrenoceptor agonists have been introduced as a new therapeutic approach, but there is growing concern about whether control of asthma may deteriorate with the regular use of these agents. We investigated the long-term effects of the beta 2 agonist salmeterol on bronchodilation and on airway hyperresponsiveness to the bronchoconstrictive agent methacholine in mild asthma.\n In a parallel, double-blind study, 24 patients with mild asthma were randomly assigned to treatment with either inhaled salmeterol (50 micrograms, twice daily) (n = 12) or placebo (n = 12) during an eight-week trial. Methacholine challenge was performed before, during, and after the treatment period. Methacholine responsiveness was measured as the provocative concentration (PC20) that caused a 20 percent decrease in the forced expiratory volume in one second (FEV1).\n There was a significant increase in FEV1 one hour after the inhalation of salmeterol (P = 0.006), which did not differ significantly on days 0, 28, and 56 of the treatment period (increase, 9.8, 9.4, and 8.8 percent of predicted FEV1, respectively; P = 0.91). On the first treatment day, salmeterol afforded significant protection against methacholine-induced bronchoconstriction, as shown by a 10-fold increase in the PC20 as compared with the value at entry (P less than 0.001). After four and eight weeks of treatment, however, the salmeterol-induced change in the PC20 was significantly attenuated (P less than 0.001) to only a twofold increase. Two and four days after treatment ended, the PC20 was not significantly different from the value before treatment (P = 0.15).\n Regular treatment of patients with mild asthma with salmeterol leads to tolerance to its protective effects against a bronchoconstrictor stimulus, in this case inhaled methacholine, despite well-maintained bronchodilation. This finding raises concern about the effectiveness of prolonged therapy with long-acting beta 2-adrenoceptor agonists in asthma.", "Tolerance to the direct bronchodilator effects of beta 2-agonists does not appear to occur in asthma. However, it is not known whether this is true for the nonbronchodilator effects of these agents, which protect the airways against bronchoconstrictive stimuli.\n We investigated whether tolerance develops to the protective effect of inhaled terbutaline on airway responsiveness to the bronchoconstrictors methacholine (which acts directly on airway smooth muscle) and AMP (which acts indirectly by stimulating the release of mediators from mast cells) during sustained treatment with terbutaline. In a randomized, double-blind, crossover study, 12 patients with mild asthma each inhaled a single dose of terbutaline (500 micrograms) or placebo before a challenge with a series of doubling doses of inhaled methacholine or AMP, before and after treatment for seven days with 500 micrograms of terbutaline four times daily or placebo.\n Before the seven days of treatment with terbutaline, a single dose of terbutaline reduced airway responsiveness to methacholine by 2.7 doubling doses (95 percent confidence interval, 1.9 to 3.5), but it had an even greater protective effect against AMP, reducing airway responsiveness by 3.8 doubling doses (95 percent confidence interval, 2.7 to 4.9; P less than 0.001). After seven days of treatment with terbutaline, the protective effect of terbutaline against methacholine decreased to 2.2 doubling doses (95 percent confidence interval, 1.3 to 3.0; P = 0.04), and that against AMP decreased even more, to 1.7 doubling doses (95 percent confidence interval, 1.1 to 2.4; P less than 0.001). By contrast, the bronchodilator response to terbutaline was unchanged during seven days of treatment with this agent.\n We observed tolerance to the nonbronchodilator actions of the inhaled beta 2-agonist terbutaline in patients with mild asthma, an effect that may be more pronounced in mast cells than in bronchial smooth muscle. This property of beta-agonists may constitute a drawback to their regular use in patients with asthma.", "The effect of slow-release aminophylline, salbutamol and a half dose combination of both was compared in children with chronic asthma. Drugs were given over three consecutive 5-week periods during which patients recorded daily peak flow measurements and symptom scores. At the end of each treatment period pulmonary function tests were done. Sixteen of twenty-nine children completed the trial satisfactorily and their results have been used for analysis. The data show slow-release aminophylline and salbutamol to be equally effective and the half dose combination as effective as either drug alone. The results suggest there may be a therapeutic advantage in combining a beta 2 agonist with theophylline when high doses of either drug alone are not fully effective or when toxic effects occur.", "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.", "The aim of the present study was to examine the efficacy of low-dose inhaled budesonide (BUD) administered via Turbuhaler once or twice daily on symptoms, lung function and bronchial hyperreactivity in children with mild asthma. One hundred and sixty-three children (mean age 9.9 yrs, 56 females/107 males) with mild asthma (forced expiratory volume in one second (FEV1) 103% of predicted, morning peak expiratory flow (PEF) 87% pred, reversibility in FEV1 3%, fall in FEV1 after exercise 10.4% from pre-exercise value) and not previously treated with inhaled steroids, were included in a double-blind, randomized, parallel-group study. After a two-week run-in period, the children received inhaled BUD 100 microg or 200 microg once daily in the morning, 100 microg twice daily or placebo for 12 weeks. Exercise and methacholine challenges were performed before and at the end of treatment. After 12 weeks of therapy, the fall in FEV1 after an exercise test was significantly less in all three BUD groups (43-5.1%) than in the placebo group (8.6%). Bronchial hyperreactivity to methacholine with the provocative dose causing a 20% fall in FEV1 decreased significantly in the BUD 100 microg twice-daily group compared with placebo (ratio at the end of treatment 156%). Changes in baseline lung function (FEV1 and PEF) were less marked than changes in bronchial responsiveness. In conclusion, low doses of inhaled budesonide, given once or twice daily, provided protection against exercise-induced bronchoconstriction in children with mild asthma and near normal lung function.", "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 addition to their bronchodilatory effects, beta(2)-agonists protect against bronchoconstriction, such as that caused by methacholine challenge. However, tachyphylaxis to this beneficial effect develops after chronic use of beta(2)-agonists. We studied whether the frequency or dose of treatment with a long-acting beta(2)-agonist (formoterol) affects the degree of bronchoprotection afforded against methacholine challenge and to compare this with the effects of a short-acting beta(2)-agonist (terbutaline).\n In a randomized, parallel group, double-blind study at two centers, patients with stable asthma of mild to moderate severity who were treated with inhaled corticosteroids were treated with formoterol 6 micrograms twice daily, 24 micrograms twice daily, 12 micrograms once daily; terbutaline 500 micrograms four times daily; or placebo. Treatments were given by dry powder inhaler for a period of 2 weeks. Of the 72 patients who were enrolled, 67 completed the study. Methacholine challenge was performed to calculate the provocative dose that caused a 20% fall in forced expiratory volume in 1 second at baseline (unprotected) after an initial 1-week run-in without beta(2)-agonists, 1 hour after the first dose of study treatment, and again 1 hour after 7 and 14 days of study treatment.\n Each of the four active treatments exhibited significant tachyphylaxis (P < 0.05) to protection against methacholine challenge when comparing first/last dose (as geometric mean protection ratio versus baseline): formoterol 24 micrograms twice daily (9.6-fold/1.6-fold), 12 micrograms once daily (7.1-fold/2.2-fold), 6 micrograms twice daily (6.2-fold/2.3-fold), and terbutaline 500 micrograms four times daily (2.9-fold/2.0-fold). There were no significant differences among treatments after 2 weeks in bronchoprotection against methacholine challenge. For all formoterol regimens, the bronchodilator response 1 hour after inhalation was maintained over the 2-week treatment period. Diurnal control of morning and evening peak flow was significantly better with formoterol 24 micrograms twice daily than with terbutaline.\n Tachyphylaxis to bronchoprotection against methacholine challenge develops after 2 weeks of therapy with formoterol, a long-acting beta(2)-agonist, at all three dosage regimens that were tested. In contrast, the bronchodilator effects of formoterol were maintained during the 2 weeks of treatment.", "The dose-response effects of inhaled beclomethasone dipropionate (BDP) and budesonide (BUD) administered b.i.d. with the aid of metered dose aerosols were studied in 128 patients (67 men and 61 women, mean age 53 years) suffering from asthma bronchiale. The study was designed as a multi-centre, double-blind, four-period cross-over study, followed by a single-blind double placebo period. BDP was administered in doses of 400 and 1000 micrograms, and BUD in doses of 400 and 800 micrograms. The results in terms of peak expiratory flow (PEF) in the morning and evening, daily symptoms score and use of inhaled beta 2-agonists did not reveal any clinically significant differences between the drugs or between high (800 micrograms BUD, 1000 micrograms BDP) and low (400 micrograms BUD/BDP) doses. However, statistically significant differences were recorded for the corresponding parameters when comparing the placebo with preceding steroid periods. Adverse effects consisting mainly of oropharyngeal candidiasis, hoarseness and cough occurred in 54 of 468 treatment months (12%). The carry-over effects of inhaled steroids are longer lasting than was previously assumed.", "We wanted to evaluate whether treatment with an inhaled corticosteroid and an inhaled long-acting beta2-agonist is more effective than an inhaled corticosteroid alone for patients using as-needed albuterol who are initiating maintenance treatment.\n To compare the efficacy and safety of twice-daily fluticasone propionate (FP) 88 microg and salmeterol 42 microg combined in a chlorofluorocarbon (CFC)-free (hydrofluoroalkane 134a) metered-dose inhaler (MDI) with the individual agents alone, each delivered through an MDI containing CFC propellants, in patient with persistent asthma previously uncontrolled with as-needed short-acting beta2-agonists alone.\n Patients with asthma (n = 283) were randomized to twice-daily treatment for 12 weeks with FP 88 microg combined with salmeterol 42 microg (FSC) in a CFC-free MDI or the individual components alone from CFC-containing MDIs.\n At endpoint, mean change from baseline in morning predose forced expiratory volume in 1 second was significantly (P < or = 0.016) greater with FSC (0.69 L) compared with FP (0.51 L) or salmeterol (0.47 L). Fewer patients treated with FSC withdrew due to worsening asthma (1%) compared with FP (3%) or salmeterol (8%; P = 0.024). FSC significantly increased (P < or = 0.002) morning and evening peak expiratory flow rate at endpoint (66.5 and 51.5 L/min, respectively) compared with FP (43.0 and 29.9 L/min, respectively) and salmeterol (29.2 and 21.6 L/min, respectively). In addition, asthma symptom scores were reduced, and percentages of days with no asthma symptoms increased in all treatment groups.\n Treatment with FSC in a CFC-free MDI is more effective than FP or salmeterol alone in asthma patients who are symptomatic taking short-acting beta2-agonists alone.", "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.", "The effect of regular inhalation of betamethasone valerate (800 microgram daily) on exercise-induced asthma has been studied in 18 adult patients. The active aerosol was compared with placebo in a double-blind cross-over study, each inhaler being used for four weeks. Exercise tests after each period of treatment were performed using a cycle ergometer, care being taken to match the oxygen uptake during exercise each time a patient was tested. Twelve patients experienced less exercise-induced fall in peak expiratory flow rate after the corticosteroid inhaler, while six did not. This effect appeared to be independent of any alteration in base-line lung function, suggesting that it was due primarily to diminution of bronchial hyperreactivity. It is suggested that this change may have been due to interference with the synthesis or release of mediator substances from mast cells.", "BACKGROUND and objective: The efficacy and safety of twice-daily inhaled salmeterol/fluticasone propionate combination (SFC) therapy have been well established in the treatment of adults and adolescents with asthma. Once-daily administration of SFC could also be appropriate in patients with mild persistent asthma. This study aimed to investigate whether once-daily SFC 50 microg/100 microg was at least as effective as fluticasone propionate (FP) 100 microg twice daily, and more effective than twice-daily placebo, over 52 weeks as initial maintenance therapy in patients with mild persistent asthma.\n This was a randomized, double-blind, double-dummy, placebo-controlled, multicentre, parallel-group study carried out in primary and secondary care. Patients aged between 12 and 79 years with a documented clinical history of asthma for > or =6 months who were currently receiving inhaled short-acting beta(2)-adrenoceptor agonists only were enrolled. Patients were randomized to receive either once-daily inhaled SFC 50 microg/100 microg, twice-daily inhaled FP 100 microg (i.e. twice the dose of FP compared with SFC) or placebo for 52 weeks. The primary efficacy endpoints were mean morning peak expiratory flow (PEF), as recorded by patients prior to the use of bronchodilator or study medication, and the rate of investigator-recorded asthma exacerbations.\n Patients receiving twice-daily FP and once-daily SFC showed greater improvements in mean morning PEF compared with those receiving placebo (FP, difference in means 20.1 L/min; 95% CI 14.7, 25.5; p < 0.001; SFC, difference in means 14.8 L/min; 95% CI 9.4, 20.2; p < 0.001). The difference in adjusted mean PEF between once-daily SFC and twice-daily FP was -5.3 L/min (95% CI -9.1, -1.6). PEF results showed that once-daily SFC was non-inferior to twice-daily FP. Over 52 weeks, there was a 35% reduction in exacerbation rates with once-daily SFC, which in this respect demonstrated superiority over placebo (p < 0.001). Non-inferiority between once-daily SFC and twice-daily FP with respect to exacerbation rates was not shown. Once-daily SFC significantly improved clinic forced expiratory flow between 25% and 75% of forced vital capacity (difference in means 0.129 L/s; p < 0.001) and clinic PEF (difference in means 10.8 L/min; p < 0.001) compared with twice-daily FP. Both treatments were well tolerated and the safety profile of each was similar to that seen with placebo.\n In patients with mild persistent asthma not previously receiving maintenance therapy, once-daily SFC 50 microg/100 microg is an effective treatment compared with placebo, and was non-inferior to twice-daily FP 100 microg with respect to mean morning PEF. However, in this study, once-daily SFC was not as efficacious as twice-daily FP in reducing asthma exacerbation rates. This study confirms the benefits of regular maintenance treatment in patients with mild persistent asthma.", "In a double-blind, randomized, parallel-group clinical trial, 340 asthmatic patients aged 12-70 years received budesonide 400 micrograms once daily in the morning, budesonide 400 micrograms once daily in the evening, budesonide 200 micrograms twice daily or placebo, for 12 weeks in addition to inhaled short-acting beta 2-agonists used as required (p.r.n.). Budesonide was given as Pulmicort Turbohaler. Peak expiratory flow rate (PEFR) increased by 20 to 30 1 min-1 in each of the active treatment groups, significantly more than in the placebo group (P < 0.01). There were no significant differences between the active treatment groups. Symptom improvement and decreased beta 2-agonist use reflected the PEFR data. Incidences of adverse events in the active treatment groups were similar to those observed in the placebo group. Budesonide 400 micrograms given once daily morning or evening is equieffective with the same total daily dose given twice daily in the treatment of mild to moderate stable asthmatics." ]	In general, these results support current guidelines, although it has given reassuring evidence against concerns over regular use of inhaled short-acting beta-2 agonists.
CD007419	[ "17101999", "20980427", "21459215", "22330964", "20855114", "21684606", "19376585", "20381871", "17917738", "17998507" ]	[ "Ranibizumab combined with verteporfin photodynamic therapy in neovascular age-related macular degeneration: year 1 results of the FOCUS Study.", "Safety and efficacy of ranibizumab in diabetic macular edema (RESOLVE Study): a 12-month, randomized, controlled, double-masked, multicenter phase II study.", "The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema.", "Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE.", "Two-year outcomes of the ranibizumab for edema of the mAcula in diabetes (READ-2) study.", "Sustained benefits from ranibizumab for macular edema following branch retinal vein occlusion: 12-month outcomes of a phase III study.", "Randomized trial of intravitreal bevacizumab alone or combined with triamcinolone versus macular photocoagulation in diabetic macular edema.", "Ranibizumab for macular edema following central retinal vein occlusion: six-month primary end point results of a phase III study.", "Intravitreal bevacizumab with or without triamcinolone for refractory diabetic macular edema; a placebo-controlled, randomized clinical trial.", "Improved vision-related function after ranibizumab treatment of neovascular age-related macular degeneration: results of a randomized clinical trial." ]	[ "To investigate the safety and efficacy of intravitreal ranibizumab treatment combined with verteporfin photodynamic therapy (PDT) in patients with predominantly classic choroidal neovascularization secondary to age-related macular degeneration.\n In this 2-year, phase I/II, multicenter, randomized, single-masked, controlled study, patients received monthly ranibizumab (0.5 mg) (n = 106) or sham (n = 56) injections. The PDT was performed 7 days before initial ranibizumab or sham treatment and then quarterly as needed.\n Proportion of patients losing fewer than 15 letters from baseline visual acuity at 12 months (primary efficacy outcome) and the incidence and severity of adverse events.\n At 12 months, 90.5% of the ranibizumab-treated patients and 67.9% of the control patients had lost fewer than 15 letters (P<.001). The most frequent ranibizumab-associated serious ocular adverse events were intraocular inflammation (11.4%) and endophthalmitis (1.9%; 4.8% if including presumed cases). On average, patients with serious inflammation had better visual acuity outcomes at 12 months than did controls. Key serious nonocular adverse events included myocardial infarctions in the PDT-alone group (3.6%) and cerebrovascular accidents in the ranibizumab-treated group (3.8%). CONCLUSION/APPLICATION TO CLINICAL PRACTICE: Ranibizumab + PDT was more efficacious than PDT alone for treating neovascular age-related macular degeneration. Although ranibizumab treatment increased the risk of serious intraocular inflammation, affected patients, on average, still experienced visual acuity benefit.", "The expression of vascular endothelial growth factor (VEGF) is elevated in diabetic macular edema (DME). Ranibizumab binds to and inhibits multiple VEGF variants. We investigated the safety and efficacy of ranibizumab in DME involving the foveal center.\n This was a 12-month, multicenter, sham-controlled, double-masked study with eyes (age>18 years, type 1 or 2 diabetes, central retinal thickness [CRT]≥300 μm, and best corrected visual acuity [BCVA] of 73-39 ETDRS letters [Early Treatment Diabetic Retinopathy Study]) randomly assigned to intravitreal ranibizumab (0.3 or 0.5 mg; n=51 each) or sham (n=49). The treatment schedule comprised three monthly injections, after which treatment could be stopped/reinitiated with an opportunity for rescue laser photocoagulation (protocol-defined criteria). After month 1, dose-doubling was permitted (protocol-defined criteria, injection volume increased from 0.05 to 0.1 ml and remained at 0.1 ml thereafter). Efficacy (BCVA and CRT) and safety were compared between pooled ranibizumab and sham arms using the full analysis set (n=151, patients receiving≥1 injection).\n At month 12, mean±SD BCVA improved from baseline by 10.3±9.1 letters with ranibizumab and declined by 1.4±14.2 letters with sham (P<0.0001). Mean CRT reduction was 194.2±135.1 μm with ranibizumab and 48.4±153.4 μm with sham (P<0.0001). Gain of ≥10 letters BCVA from baseline occurred in 60.8% of ranibizumab and 18.4% of sham eyes (P<0.0001). Safety data were consistent with previous studies of intravitreal ranibizumab.\n Ranibizumab is effective in improving BCVA and is well tolerated in DME. Future clinical trials are required to confirm its long-term efficacy and safety.", "To demonstrate superiority of ranibizumab 0.5 mg monotherapy or combined with laser over laser alone based on mean average change in best-corrected visual acuity (BCVA) over 12 months in diabetic macular edema (DME).\n A 12-month, randomized, double-masked, multicenter, laser-controlled phase III study.\n We included 345 patients aged ≥18 years, with type 1 or 2 diabetes mellitus and visual impairment due to DME.\n Patients were randomized to ranibizumab + sham laser (n = 116), ranibizumab + laser (n = 118), or sham injections + laser (n = 111). Ranibizumab/sham was given for 3 months then pro re nata (PRN); laser/sham laser was given at baseline then PRN (patients had scheduled monthly visits).\n Mean average change in BCVA from baseline to month 1 through 12 and safety.\n Ranibizumab alone and combined with laser were superior to laser monotherapy in improving mean average change in BCVA letter score from baseline to month 1 through 12 (+6.1 and +5.9 vs +0.8; both P<0.0001). At month 12, a significantly greater proportion of patients had a BCVA letter score ≥15 and BCVA letter score level >73 (20/40 Snellen equivalent) with ranibizumab (22.6% and 53%, respectively) and ranibizumab + laser (22.9% and 44.9%) versus laser (8.2% and 23.6%). The mean central retinal thickness was significantly reduced from baseline with ranibizumab (-118.7 μm) and ranibizumab + laser (-128.3 μm) versus laser (-61.3 μm; both P<0.001). Health-related quality of life, assessed through National Eye Institute Visual Function Questionnaire (NEI VFQ-25), improved significantly from baseline with ranibizumab alone and combined with laser (P<0.05 for composite score and vision-related subscales) versus laser. Patients received ∼7 (mean) ranibizumab/sham injections over 12 months. No endophthalmitis cases occurred. Increased intraocular pressure was reported for 1 patient each in the ranibizumab arms. Ranibizumab monotherapy or combined with laser was not associated with an increased risk of cardiovascular or cerebrovascular events in this study.\n Ranibizumab monotherapy and combined with laser provided superior visual acuity gain over standard laser in patients with visual impairment due to DME. Visual acuity gains were associated with significant gains in VFQ-25 scores. At 1 year, no differences were detected between the ranibizumab and ranibizumab + laser arms. Ranibizumab monotherapy and combined with laser had a safety profile in DME similar to that in age-related macular degeneration.\n Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.", "To evaluate the efficacy and safety of intravitreal ranibizumab in diabetic macular edema (DME) patients.\n Two parallel, methodologically identical, phase III, multicenter, double-masked, sham injection-controlled, randomized studies.\n Adults with vision loss from DME (best-corrected visual acuity [BCVA], 20/40-20/320 Snellen equivalent) and central subfield thickness ≥275 μm on time-domain optical coherence tomography (OCT).\n Monthly intravitreal ranibizumab (0.5 or 0.3 mg) or sham injections. Macular laser was available per-protocol-specified criteria.\n Proportion of patients gaining ≥15 letters in BCVA from baseline at 24 months.\n In RISE (NCT00473330), 377 patients were randomized (127 to sham, 125 to 0.3 mg, 125 to 0.5 mg). At 24 months, 18.1% of sham patients gained ≥15 letters versus 44.8% of 0.3-mg (P<0.0001; difference vs sham adjusted for randomization stratification factors, 24.3%; 95% confidence interval [CI], 13.8-34.8) and 39.2% of 0.5-mg ranibizumab patients (P<0.001; adjusted difference, 20.9%; 95% CI, 10.7-31.1). In RIDE (NCT00473382), 382 patients were randomized (130 to sham, 125 to 0.3 mg, 127 to 0.5 mg). Significantly more ranibizumab-treated patients gained ≥15 letters: 12.3% of sham patients versus 33.6% of 0.3-mg patients (P<0.0001; adjusted difference, 20.8%; 95% CI, 11.4-30.2) and 45.7% of 0.5-mg ranibizumab patients (P<0.0001; adjusted difference, 33.3%; 95% CI, 23.8-42.8). Significant improvements in macular edema were noted on OCT, and retinopathy was less likely to worsen and more likely to improve in ranibizumab-treated patients. Ranibizumab-treated patients underwent significantly fewer macular laser procedures (mean of 1.8 and 1.6 laser procedures over 24 months in the sham groups vs 0.3-0.8 in ranibizumab groups). Ocular safety was consistent with prior ranibizumab studies; endophthalmitis occurred in 4 ranibizumab patients. The total incidence of deaths from vascular or unknown causes, nonfatal myocardial infarctions, and nonfatal cerebrovascular accidents, which are possible effects from systemic vascular endothelial growth factor inhibition, was 4.9% to 5.5% of sham patients and 2.4% to 8.8% of ranibizumab patients.\n Ranibizumab rapidly and sustainably improved vision, reduced the risk of further vision loss, and improved macular edema in patients with DME, with low rates of ocular and nonocular harm.\n Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.", "To determine the long-term effects of ranibizumab (RBZ) in patients with diabetic macular edema (DME).\n Prospective, randomized, interventional, multicenter clinical trial.\n One hundred twenty-six patients with DME.\n Subjects were randomized 1:1:1 to receive 0.5 mg RBZ at baseline and months 1, 3, and 5 (group 1), focal or grid laser photocoagulation at baseline and month 3 if needed (group 2), or a combination of 0.5 mg RBZ and focal or grid laser at baseline and month 3 (group 3). Starting at month 6, if retreatment criteria were met, all subjects could be treated with RBZ.\n The mean change from baseline in best-corrected visual acuity (BCVA) at month 24.\n After the primary end point at month 6, most patients in all groups were treated only with RBZ, and the mean number of injections was 5.3, 4.4, and 2.9 during the 18-month follow-up period in groups 1, 2, and 3, respectively. For the 33 patients in group 1, 34 patients in group 2, and 34 patients in group 3 who remained in the study through 24 months, the mean improvement in BCVA was 7.4, 0.5, and 3.8 letters at the 6-month primary end point, compared with 7.7, 5.1, and 6.8 letters at month 24, and the percentage of patients who gained 3 lines or more of BCVA was 21, 0, and 6 at month 6, compared with 24, 18, and 26 at month 24. The percentage of patients with 20/40 or better Snellen equivalent at month 24 was 45% in group 1, 44% in group 2, and 35% in group 3. Mean foveal thickness (FTH), defined as center subfield thickness, at month 24 was 340 μm, 286 μm, and 258 μm for groups 1, 2, and 3, respectively, and the percentage of patients with center subfield thickness of 250 μm or less was 36%, 47%, and 68%, respectively.\n Intraocular injections of RBZ provided benefit for patients with DME for at least 2 years, and when combined with focal or grid laser treatments, the amount of residual edema was reduced, as were the frequency of injections needed to control edema.\n Proprietary or commercial disclosure may be found after the references.\n Copyright © 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.", "Assess 12-month efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema after branch retinal vein occlusion (BRVO).\n Prospective, randomized, sham injection-controlled, double-masked, multicenter trial.\n A total of 397 patients with macular edema after BRVO.\n Eligible patients were randomized 1:1:1 to 6 monthly injections of 0.3 mg or 0.5 mg ranibizumab or sham injections. After 6 months, all patients with study eye best-corrected visual acuity (BCVA) ≤20/40 or central subfield thickness ≥250 μm were to receive ranibizumab. Patients could receive rescue laser treatment once during the treatment period and once during the observation period if criteria were met.\n The main efficacy outcome reported is mean change from baseline BCVA letter score at month 12. Additional visual and anatomic parameters were assessed.\n Mean (95% confidence interval) change from baseline BCVA letter score at month 12 was 16.4 (14.5-18.4) and 18.3 (15.8-20.9) in the 0.3 mg and 0.5 mg groups, respectively, and 12.1 (9.6-14.6) in the sham/0.5 mg group (P<0.01, each ranibizumab group vs. sham/0.5 mg). The percentage of patients who gained ≥15 letters from baseline BCVA at month 12 was 56.0% and 60.3% in the 0.3 mg and 0.5 mg groups, respectively, and 43.9% in the sham/0.5 mg group. On average, there was a marked reduction in central foveal thickness (CFT) after the first as-needed injection of 0.5 mg ranibizumab in the sham/0.5 mg group, which was sustained through month 12. No new ocular or nonocular safety events were identified.\n At month 12, treatment with ranibizumab as needed during months 6-11 maintained, on average, the benefits achieved by 6 monthly ranibizumab injections in patients with macular edema after BRVO, with low rates of ocular and nonocular safety events. In the sham/0.5 mg group, treatment with ranibizumab as needed for 6 months resulted in rapid reduction in CFT to a similar level as that in the 0.3 mg ranibizumab treatment group and an improvement in BCVA, but not to the extent of that in the 2 ranibizumab groups. Intraocular injections of ranibizumab provide an effective treatment for macular edema after BRVO.\n Proprietary or commercial disclosure may be found after the references.\n Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.", "To compare the results of intravitreal bevacizumab (IVB) injection alone or in combination with intravitreal triamcinolone acetonide (IVT) versus macular laser photocoagulation (MPC) as a primary treatment of diabetic macular edema (DME).\n Randomized 3-arm clinical trial.\n A total of 150 eyes of 129 patients with clinically significant DME and no previous treatment.\n The eyes were randomly assigned to 1 of the 3 study arms: the IVB group, patients who received 1.25 mg IVB (50 eyes); the IVB/IVT group, patients who received 1.25 mg of IVB and 2 mg of IVT (50 eyes); and the MPC group, patients who underwent focal or modified grid laser (50 eyes). Retreatment was performed at 12-week intervals whenever indicated.\n Change in best-corrected visual acuity (VA) at week 24.\n VA changes among the groups were statistically significant at 6 (P<0.001) and 24 (P = 0.012) weeks. The significant treatment effect was demonstrated in the IVB group at all follow-up visits and in the IVB/IVT group at 6 and 12 weeks. VA changes +/- standard deviation at 36 weeks were -0.28+/-0.25, -0.04+/-0.33, and +0.01+/-0.27 logarithm of minimum angle of resolution in the IVB, IVB/IVT, and MPC groups, respectively (P = 0.053). Significant central macular thickness (CMT) reduction was observed in all groups only up to 6 weeks; however, CMT changes were not significant among the groups in all visits. Overall, retreatment was required for 27 eyes up to 36 weeks (14 in the IVB group, 10 in the IVB/IVT group, and 3 in the MPC group). In the IVB group, in which a greater VA improvement was observed, only 1 injection was required in 72% of the cases. VA improvement >2 Snellen lines at 36 weeks was detected in 37%, 25%, and 14.8% of patients in the IVB, IVB/IVT, and MPC groups, respectively.\n Intravitreal bevacizumab injection in patients with DME yielded a better visual outcome at 24 weeks compared with macular photocoagulation. A change in CMT beyond the 6-week time point that corresponded to the vision change was not detected. No adjunctive effect of IVT was demonstrated.\n The author(s) have no proprietary or commercial interest in any materials discussed in this article.", "To assess the efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema after central retinal vein occlusion (CRVO).\n Prospective, randomized, sham injection-controlled, double-masked, multicenter clinical trial.\n A total of 392 patients with macular edema after CRVO.\n Eligible patients were randomized 1:1:1 to receive monthly intraocular injections of 0.3 or 0.5 mg of ranibizumab or sham injections.\n The primary efficacy outcome measure was mean change from baseline best-corrected visual acuity (BCVA) letter score at month 6. Secondary outcomes included other parameters of visual function and central foveal thickness (CFT).\n Mean (95% confidence interval [CI]) change from baseline BCVA letter score at month 6 was 12.7 (9.9-15.4) and 14.9 (12.6-17.2) in the 0.3 mg and 0.5 mg ranibizumab groups, respectively, and 0.8 (-2.0 to 3.6) in the sham group (P<0.0001 for each ranibizumab group vs. sham). The percentage of patients who gained > or =15 letters in BCVA at month 6 was 46.2% (0.3 mg) and 47.7% (0.5 mg) in the ranibizumab groups and 16.9% in the sham group (P<0.0001 for each ranibizumab group vs. sham). At month 6, significantly more ranibizumab-treated patients (0.3 mg = 43.9%; 0.5 mg = 46.9%) had BCVA of > or = 20/40 compared with sham patients (20.8%; P<0.0001 for each ranibizumab group vs. sham), and CFT had decreased by a mean of 434 microm (0.3 mg) and 452 microm (0.5 mg) in the ranibizumab groups and 168 microm in the sham group (P<0.0001 for each ranibizumab group vs. sham). The median percent reduction in excess foveal thickness at month 6 was 94.0% and 97.3% in the 0.3 mg and 0.5 mg groups, respectively, and 23.9% in the sham group. The safety profile was consistent with previous phase III ranibizumab trials, and no new safety events were identified in patients with CRVO.\n Intraocular injections of 0.3 mg or 0.5 mg ranibizumab provided rapid improvement in 6-month visual acuity and macular edema following CRVO, with low rates of ocular and nonocular safety events.\n Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.", "To evaluate the effect of three intravitreal injections of bevacizumab (IVB) alone or combined with triamcinolone (IVT) in the first injection for treatment of refractory diabetic macular edema (DME).\n In this prospective, placebo-controlled, randomized clinical trial, 115 eyes of 101 patients with refractory DME were included. Subjects were randomly assigned to one of the three study arms: 1) three injections of IVB (1.25 mg/0.05 ml) at 6-week intervals, 2) combined IVB and IVT (1.25 mg/0.05 ml and 2 mg/0.05 ml respectively) followed by two injections of IVB at 6-week intervals, and 3) sham injection (control group). The primary outcome measure was change in central macular thickness (CMT). Secondary outcome measures were change in best-corrected logMAR visual acuity (BCVA ) and incidence of potential adverse events.\n Central macular thickness was reduced significantly in both the IVB and IVB/IVT groups. At week 24, CMT change compared to the baseline was -95.7 microm (95% CI, -172.2 to -19.26) in the IVB group, -92.1 microm (95% CI, -154.4 to -29.7) in the IVB/IVT group, and 34.9 microm (95% CI, 7.9 to 61.9) in the control group. There was a significant difference between the IVB and control groups (P = 0.012) and between the IVB/IVT and control groups (P = 0.022). Improvement of BCVA was initiated at weeks 6 and 12 in the IVB/IVT and IVB groups respectively. In terms of BCVA change compared to the baseline at 24 weeks, the differences between the IVB and control groups (P = 0.01) and also between the IVB/IVT and control groups (P = 0.006) were significant. No significant differences were detected in the changes of CMT and BCVA between the IVB and IVB/IVT groups (P = 0.99). Anterior chamber reaction was noticed in eight (19.5%) and seven (18.9%) eyes respectively in the IVB and IVB/IVT groups the day after injection, and it resolved with no sequel. Elevation of IOP occurred in three eyes (8.1%) in the IVB/IVT group.\n Three consecutive intravitreal injections of bevacizumab had a beneficial effect on refractory DME in terms of CMT reduction and BCVA improvement. Addition of triamcinolone in the first injection seemed to induce earlier visual improvement; however, it did not show any significant additive effect later during follow-up.", "To examine the effects of ranibizumab on patient-reported visual function using the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) in patients with neovascular age-related macular degeneration (AMD).\n In MARINA, a randomized, double-masked clinical trial, 716 patients with AMD with recent disease progression and minimally classic or occult with no classic lesion component were randomized 1:1:1 to monthly intravitreal ranibizumab (0.3 or 0.5 mg) or sham injections. The NEI VFQ-25 was administered at 0, 1, 2, 3, 6, 9, 12, 18, and 24 months. Main Outcome Measure Mean change from baseline in NEI VFQ-25 scores at 12 and 24 months.\n At 12 months, ranibizumab-treated patients (0.3 mg [n = 238] and 0.5 mg [n = 240]) had mean improvements in NEI VFQ-25 composite scores of +5.2 (95% confidence interval [CI], 3.5 to 6.9) and +5.6 (95% CI, 3.9 to 7.4), respectively; sham-injected patients (n = 238) had a mean decline of -2.8 (95% CI, -4.6 to -1.1; P < .001 vs each dose). Ranibizumab-treated patients were more likely to improve in near activities, distance activities, and vision-specific dependency through 24 months.\n In MARINA, ranibizumab-treated patients were more likely than sham-treated patients to report visual function improvements at 12 and 24 months.\n Treatment of neovascular AMD with ranibizumab can improve patient-reported visual function in a meaningful way compared with sham treatments.\n clinicaltrials.gov Identifier: NCT00056836." ]	There is moderate quality evidence that antiangiogenic drugs provide a definite, but small, benefit compared to current therapeutic options for DMO, i.e. grid laser photocoagulation, or no treatment when laser is not an option. The quality and quantity of the evidence was larger for ranibizumab, but there was little power to investigate drug differences. Most data were obtained at one year, and a long-term confirmation is needed, since DMO is a chronic condition. Safety of both drug and the intravitreal injection procedure were good in the trials, but further long-term data are needed to exclude small, but clinically important differences regarding systemic adverse events.
CD004742	[ "15339761", "12114886", "14961887", "14764128", "14501737", "15662490", "15821528" ]	[ "Pharmacological treatment of women awaiting surgery for stress urinary incontinence.", "Duloxetine versus placebo in the treatment of stress urinary incontinence.", "Duloxetine versus placebo in the treatment of European and Canadian women with stress urinary incontinence.", "Duloxetine vs placebo in the treatment of stress urinary incontinence: a four-continent randomized clinical trial.", "Duloxetine versus placebo for the treatment of North American women with stress urinary incontinence.", "Impact of duloxetine on quality of life for women with symptoms of urinary incontinence.", "A randomized controlled trial of duloxetine alone, pelvic floor muscle training alone, combined treatment and no active treatment in women with stress urinary incontinence." ]	[ "Duloxetine, a serotonin/norepinephrine reuptake inhibitor, has been effective in the treatment of mild and moderate stress urinary incontinence. The aim of this trial was to assess its efficacy for women with severe stress urinary incontinence.\n One hundred nine women, aged 33-75 years, enrolled into this double-blind, randomized, placebo-controlled study. Subjects had to have a predominant symptom of stress urinary incontinence with an incontinence episode frequency 14 per week or more, pure urodynamic stress urinary incontinence, and continence surgery already scheduled. Women were randomized to placebo (n = 54) or duloxetine 80 mg/d (n = 55) for 4 weeks, escalated to 120 mg/d for 4 weeks. Assessment variables included incontinence episode frequency, continence pad use, the Incontinence Quality of Life (I-QOL) questionnaire, and the Willingness to Consider Surgery rating. A responder was defined as a subject with an incontinence episode frequency reduction of 50% or more.\n There were significant improvements with duloxetine compared with placebo in incontinence episode frequency (-60% versus -27%, P <.001), I-QOL score (+10.6 versus +2.4, P =.003), and pad use (-34.5% versus -4.8%, P =.008). At the conclusion of the 8-week study, 10/49 (20%) duloxetine-treated women were no longer interested in surgery, compared with 0/45 placebo-treated women (P =.001). Duloxetine-treated subjects were significantly more likely to be classified as responders (relative risk 4.68, 95% confidence interval 2.27-9.66). The number of subjects-needed-to-treat to gain an additional incontinence episode frequency responder with duloxetine was 2.02. All duloxetine responses were observed within 2 weeks. Side effects and discontinuations because of side effects were significantly more common with duloxetine.\n The data support duloxetine's efficacy in women with severe stress urinary incontinence and suggest that some women responding to duloxetine may reconsider their willingness to undergo surgery.", "The purpose of this study was to assess the efficacy and safety of duloxetine, a selective inhibitor of serotonin and norepinephrine reuptake, in the treatment of stress urinary incontinence.\n A double-blind, randomized, placebo-controlled study was conducted in 553 women aged 18 to 65 years with a predominant symptom of stress urinary incontinence. Subjects were randomized to placebo (n = 138 women) or duloxetine at one of three doses (20 mg/d, n = 138 women; 40 mg/d, n = 137 women; or 80 mg/d, n = 140 women). Outcome variables that were assessed after 12 weeks of treatment included incontinence episode frequency recorded in a real-time diary and answers provided to the Patient Global Impression of Improvement scale and the Incontinence Quality of Life questionnaire.\n Duloxetine was associated with significant and dose-dependent decreases in incontinence episode frequency that paralleled improvements that were observed in the Patient Global Impression of Improvement scale and the Incontinence Quality of Life questionnaire. The median incontinence episode frequency decrease with the use of the pooled diary analysis with placebo was 41% compared with 54% for duloxetine 20 mg per day (P =.06), 59% for duloxetine 40 mg per day (P =.002), and 64% for duloxetine 80 mg per day (P <.001). One half of the subjects at the 80 mg per day dose had a > or = 64% reduction in incontinence episode frequency (P <.001 vs placebo); 67% had > or = 50% reduction (P =.001 vs placebo). These improvements were observed despite significant concurrent dose-dependent increases in the average voiding interval in the duloxetine groups compared with the placebo group. Similar statistically significant improvements were demonstrated in a subgroup of 163 subjects who had more severe stress urinary incontinence (> or = 14 incontinence episode frequency per week; 49%-64% reduction in incontinence episode frequency in the duloxetine groups compared with 30% in the placebo group). Discontinuation rates for adverse events were 5% for placebo and 9%, 12%, and 15% for duloxetine 20, 40, and 80 mg per day, respectively (P =.04). Nausea was the most common symptom that led to discontinuation. None of the adverse events that were reported were considered to be clinically severe.\n This trial provides evidence for the efficacy and safety of duloxetine as a pharmacologic agent for the treatment of stress urinary incontinence.", "To assess the efficacy and safety of duloxetine in women with stress urinary incontinence.\n Randomised double-blind, placebo-controlled clinical trial.\n Fort-six centres in seven European countries and Canada.\n Four hundred and ninety-four women aged 24-83 years identified as having predominant symptoms of stress urinary incontinence using a clinical algorithm that was 100% predictive of urodynamic stress urinary incontinence in a subgroup of 34 women.\n The case definition included a predominant symptom of stress urinary incontinence with a weekly incontinence episode frequency > or =7, the absence of predominant symptoms of urge incontinence, normal diurnal and nocturnal frequencies, a bladder capacity > or =400 mL and both a positive cough stress test and positive stress pad test. Subjects completed two urinary diaries prior to randomisation and three diaries during the active treatment phase of the study, each completed during the week prior to monthly visits. Subjects also completed quality of life questionnaires at each visit. Safety was assessed by the evaluation of treatment-emergent adverse events, discontinuation of treatment because of adverse events, serious adverse events, vital sign measurements, electrocardiograms (ECG) and clinical laboratory tests.\n After a two-week placebo lead-in, women received placebo or duloxetine 40 mg BD for 12 weeks.\n The percentage decrease in incontinence episode frequency and the change in the Incontinence Quality of Life (I-QOL) questionnaire total score were prespecified as co-primary outcome variables in the protocol.\n Incontinence episode frequency decreased significantly with duloxetine compared with placebo (median decrease of 50%vs 29%; P= 0.002) with comparable improvements in the more severely incontinent subgroup (those experiencing at least 14 incontinence episodes per week at baseline; 56%vs 27% decreases; P < 0.001). The primary analysis of I-QOL scores did not reveal a significant difference between treatment groups, due primarily to the carrying forward of low scores from patients who discontinued treatment very early due to duloxetine-associated adverse events. The increase in I-QOL scores was significantly greater for duloxetine than for placebo at each of the three postrandomisation visits after 4, 8, and 12 weeks of treatment. Discontinuation rates for adverse events were higher for duloxetine (22%vs 5%; P < 0.001) with nausea being the most common reason for discontinuation (5.3%). Nausea tended to be mild to moderate, not progressive, and transient.\n The findings support duloxetine as a potential treatment for women with stress urinary incontinence.", "To further assess, in a phase 3 study, treatment with duloxetine for women with stress urinary incontinence (SUI) in other geographical regions, including Argentina, Australia, Brazil, Finland, Poland, South Africa and Spain, as previous trials in North America and Europe provided evidence for the safety and efficacy of duloxetine as a pharmacological treatment for SUI in women.\n The study included 458 women aged 27-79 years enrolled in a double-blind, placebo-controlled trial. The patients with predominantly SUI were identified using a validated clinical algorithm. They were randomly assigned to receive placebo (231) or duloxetine 40 mg twice daily (227) for 12 weeks. The primary outcome variables included the incontinence episode frequency (IEF) and the Incontinence Quality of Life (I-QOL) questionnaire. Van Elteren's test was used to analyse the percentage changes in IEF where the stratification variable was weekly baseline IEF (IEF < 14 and > or = 14). Analysis of covariance was used to analyse I-QOL scores.\n The mean baseline IEF was 18.4/week; 55% of patients had a baseline IEF of > or = 14. There was a significantly greater median decrease in IEF with duloxetine with placebo (54% vs 40%, P = 0.05), with comparable significant improvements in quality of life (I-QOL score increases of 10.3 vs 6.4, P = 0.007). The improvements with duloxetine were associated with significantly greater increases in voiding intervals than with placebo (20.4 vs 8.5 min, P < 0.001). The placebo response was 10.7% and 12.5% higher than those reported in two European and North American phase 3 trials. This may have been related to more patients being naïve for incontinence management in the current trial. Discontinuation rates for adverse events were 1.7% for placebo and 17.2% for duloxetine (P < 0.001), with nausea being the most common reason for discontinuation (3.1%); it was the most common adverse event with duloxetine, but was mild or moderate in most (81%), did not worsen in any patient and resolved within 7 days in 60% and within 1 month in 86% of continuing patients; 88% of women who experienced nausea while taking duloxetine completed the trial.\n These results show improvements in incontinence and quality of life with duloxetine 40 mg twice daily for 12 weeks that are in keeping with those reported in two other recently completed phase 3 trials in Europe and North America.", "Duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, increases rhabdosphincter contractility via the stimulation of pudendal motor neuron alpha-1 adrenergic and 5-hydroxytryptamine-2 receptors. In this first phase 3 study we assessed the efficacy and safety of duloxetine in women with stress urinary incontinence (SUI).\n A total of 683 North American women 22 to 84 years old were enrolled in this double-blind, placebo controlled study. The case definition included a predominant symptom of SUI with a weekly incontinence episode frequency (IEF) of 7 or greater, the absence of predominant symptoms of urge incontinence, normal diurnal and nocturnal frequency, a bladder capacity of 400 ml or greater, and a positive cough stress test and stress pad test. After a 2-week placebo lead-in period subjects were randomly assigned to receive placebo (339) or 80 mg duloxetine daily (344) as 40 mg twice daily for 12 weeks. Primary outcome variables included IEF and an incontinence quality of life questionnaire. Van Elteren's test was used to analyze percent changes in IEF with a stratification variable of weekly baseline IEF (less than 14 and 14 or greater). ANCOVA was used to analyze incontinence quality of life scores.\n Mean baseline IEF was 18 weekly and 436 subjects (64%) had a baseline IEF of 14 or greater. There was a significant decrease in IEF with duloxetine compared with placebo (50% vs 27%, p <0.001) with comparably significant improvements in quality of life (11.0 vs 6.8, p <0.001). Of subjects on duloxetine 51% had a 50% to 100% decrease in IEF compared with 34% of those on placebo (p <0.001). These improvements with duloxetine were associated with a significant increases in the voiding interval compared with placebo (20 vs 2 minutes, p <0.001) and they were observed across the spectrum of incontinence severity. The discontinuation rate for adverse events was 4% for placebo and 24% for duloxetine (p <0.001) with nausea the most common reason for discontinuation (6.4%). Nausea, which was also the most common side effect, tended to be mild to moderate and transient, usually resolving after 1 week to 1 month. Of the 78 women who experienced treatment emergent nausea while taking duloxetine 58 (74%) completed the trial.\n These phase 3 data are consistent with phase 2 data and they provide further evidence for the safety and efficacy of duloxetine as a pharmacological agent for the treatment of women with SUI.", "The objective of this study was to evaluate the effectiveness of duloxetine in improving quality of life among women with stress and mixed urinary incontinence. The study included 451 women with self-reported stress incontinence episodes (>or=1/week) who were randomized to duloxetine (40 mg BID) or placebo in a double-blind, usual care design. Patients and physicians were allowed to titrate, augment, and/or discontinue treatment. Concomitant treatments were permitted. The primary outcome was the Incontinence Quality of Life Questionnaire (I-QOL) score, with assessments at 3, 6, and 9 months. Other measures included the Patient Global Impression of Improvement (PGI-I) and adverse events. The adjusted mean change in I-QOL total score was greater in the duloxetine group than in the placebo group and at a level comparable to that found in previous clinical trials, but the difference between placebo and duloxetine was not statistically significant in the intent-to-treat, last observation carried forward (LOCF) analysis. The difference approached statistical significance in favor of duloxetine at 3 months (p=0.07). PGI-I ratings did not demonstrate significant superiority for duloxetine in LOCF analysis; however, study completers taking duloxetine were significantly more likely to rate themselves as \"better\" (70.2%) than completers taking placebo (50.8%, p<0.05). Women utilized a variety of treatment methods including pelvic floor muscle training, estrogen, anticholinergic medication, weight reduction, and smoking cessation. In this study, while mean I-QOL change scores were numerically higher for the duloxetine group than mean change scores for the placebo group, this difference was not statistically significant. Among women who completed the study on study drug, a significantly greater proportion of duloxetine women versus placebo women rated their condition to be better.", "We primarily compared the effectiveness of combined pelvic floor muscle training (PFMT) and duloxetine with imitation PFMT and placebo for 12 weeks in women with stress urinary incontinence (SUI). In addition, we compared the effectiveness of combined treatment with single treatments, single treatments with each other and single treatments with no treatment.\n This blinded, doubly controlled, randomized trial enrolled 201 women 18 to 75 years old with SUI at 17 incontinence centers in the Netherlands, United Kingdom and United States. Women averaged 2 or more incontinence episodes daily and were randomized to 1 of 4 combinations of 80 mg duloxetine daily, placebo, PFMT and imitation PFMT, including combined treatment (in 52), no active treatment (in 47), PFMT only (in 50) and duloxetine only (in 52). The primary efficacy measure was incontinence episode frequency. Other efficacy variables included the number of continence pads used and the Incontinence Quality of Life questionnaire score.\n The intent to treat population incontinence episode frequency analysis demonstrated the superiority of duloxetine with or without PFMT compared with no treatment or with PFMT alone. However, pad and Incontinence Quality of Life analyses suggested greater improvement with combined treatment than single treatment. A completer population analysis demonstrated the efficacy of duloxetine with or without PFMT and suggested combined treatment was more effective than either treatment alone.\n The data support significant efficacy of combined PFMT and duloxetine in the treatment of women with SUI. We hypothesize that complementary modes of action of duloxetine and PFMT may result in an additive effect of combined treatment." ]	The available evidence suggests that duloxetine treatment can significantly improve the quality of life of patients with stress urinary incontinence, but it is unclear whether or not benefits are sustainable. Adverse effects are common but not serious. About one in three participants allocated duloxetine reported adverse effects (most commonly nausea) related to treatment, and about one in eight allocated duloxetine stopped treatment as a consequence.
CD001155	[ "15860827", "10663363", "10091204", "3035879", "15885294", "8135445", "17998225", "15728210", "15664003", "12609940", "9875874" ]	[ "Randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D3) for prevention of fractures in primary care.", "Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group.", "HRT and Vit D in prevention of non-vertebral fractures in postmenopausal women; a 5 year randomized trial.", "Postmenopausal osteoporosis: no effect of three years treatment with 1,25-dihydroxycholecalciferol.", "Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial.", "Slow-release sodium fluoride in the management of postmenopausal osteoporosis. A randomized controlled trial.", "Effect of annual intramuscular vitamin D on fracture risk in elderly men and women--a population-based, randomized, double-blind, placebo-controlled trial.", "Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) study.", "Menatetrenone and vitamin D2 with calcium supplements prevent nonvertebral fracture in elderly women with Alzheimer's disease.", "Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial.", "Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial." ]	[ "To assess whether supplementation with calcium and cholecaliferol (vitamin D3) reduces the risk of fracture in women with one or more risk factors for fracture of the hip.\n Pragmatic open randomised controlled trial.\n Practice nurse led clinics in primary care.\n 3314 women aged 70 and over with one or more risk factors for hip fracture: any previous fracture, low body weight (< 58 kg), smoker, family history of hip fracture, or fair or poor self reported health.\n Daily oral supplementation using 1000 mg calcium with 800 IU cholecaliferol and information leaflet on dietary calcium intake and prevention of falls, or leaflet only (control group).\n Primary outcome measure was all clinical fractures and secondary outcome measures were adherence to treatment, falls, and quality of life (measured with the SF-12).\n 69% of the women who completed the follow-up questionnaire at 24 months were still taking supplements (55% with inclusion of randomised participants known to be alive). After a median follow-up of 25 months (range 18 to 42 months), clinical fracture rates were lower than expected in both groups but did not significantly differ for all clinical fractures (odds ratio for fracture in supplemented group 1.01, 95% confidence interval 0.71 to 1.43). The odds ratio for hip fracture was 0.75 (0.31 to 1.78). The odds of a woman having a fall at six and 12 months was 0.99 and 0.98, respectively. Quality of life did not significantly differ between the groups.\n We found no evidence that calcium and vitamin D supplementation reduces the risk of clinical fractures in women with one or more risk factors for hip fracture. Registration ISRCTN26118436, controlled trials registry.", "The purpose of this randomized, double-masked, placebo-controlled study was to determine the efficacy and safety of risedronate in the prevention of vertebral fractures in postmenopausal women with established osteoporosis. The study was conducted at 80 study centers in Europe and Australia. Postmenopausal women (n = 1226) with two or more prevalent vertebral fractures received risedronate 2.5 or 5 mg/day or placebo; all subjects also received elemental calcium 1000 mg/day, and up to 500 IU/day vitamin D if baseline levels were low. The study duration was 3 years; however, the 2.5 mg group was discontinued by protocol amendment after 2 years. Lateral spinal radiographs were taken annually for assessment of vertebral fractures, and bone mineral density was measured by dual-energy X-ray absorptiometry at 6-month intervals. Risedronate 5 mg reduced the risk of new vertebral fractures by 49% over 3 years compared with control (p<0.001). A significant reduction of 61% was seen within the first year (p = 0.001). The fracture reduction with risedronate 2.5 mg was similar to that in the 5 mg group over 2 years. The risk of nonvertebral fractures was reduced by 33% compared with control over 3 years (p = 0.06). Risedronate significantly increased bone mineral density at the spine and hip within 6 months. The adverse-event profile of risedronate, including gastrointestinal adverse events, was similar to that of control. Risedronate 5 mg provides effective and well-tolerated therapy for severe postmenopausal osteoporosis, reducing the incidence of vertebral fractures and improving bone density in women with established disease.", "We investigated the incidence of new non-vertebral fractures during HRT or low-dose vitamin (Vit) D3 supplementation in a 5-year prospective trial.\n A total of 464 early postmenopausal women, (a subgroup of the Kuopio Osteoporosis Study, n = 13,100) were randomized to four groups: (1) HRT, a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate; (2) Vit D (300 IU/day and 100 IU/day during the fifth years); (3) HRT + Vit D; and (4) placebo. Lumbar (L2-4) and femoral neck bone mineral densities (BMD) were determined by dual X-ray absorptiometry (DXA) at baseline, after 2.5 and 5 years of treatment. All new symptomatic non-vertebral, radiographically defined fractures were recorded.\n Altogether, 368 women (79%) completed the 5 year treatment. In all, 32 women had 39 non-vertebral fractures during a mean of 4.3 year follow-up (HRT 4, Vit D 10, HRT + Vit D 8 and placebo 17). The reduction in the incidence of new non-vertebral fractures was significant in women with HRT alone (P = 0.032) when adjusted by baseline BMD and previous fractures; observed also with the intention-to-treat principle (P = 0.048). When the HRT groups were pooled, HRT showed a significantly lower incidence of new non-vertebral fractures (P = 0.042) than women receiving placebo and also after adjusting as above (P = 0.016); both in valid-case and in the intention-to-treat analysis. In the Vit D group, the fracture incidence was non-significantly decreased (P = 0.229) in comparison with the placebo group. The estimated risk of new non-vertebral fractures among women treated with HRT alone was 0.29 (95% CI, 0.10-0.90) and with Vit D 0.47 (95% CI, 0.20-1.14) and with HRT + Vit D 0.44 (95% CI, 0.17-1.15), in comparison with the placebo group (adjusted by femoral BMD and previous fractures).\n This study is the first prospective trial confirming the beneficial effect of HRT on prevention of peripheral fractures in non-osteoporotic postmenopausal women. The effect of low-dose Vit D remains to be proved.", "The therapeutic effect of 1,25-dihydroxycholecalciferol (1,25(OH)2D3) in postmenopausal osteoporosis was tested in a single blind, randomized prospective study. Thirty-nine women, 50-65 years of age, were treated for three years with 0.5 microgram 1,25(OH)2D3 daily. In a control group, 37 women were given 400 IU vitamin D3 daily. There was no significant difference in annual bone loss from the distal or proximal forearm between the groups. New vertebral fractures were evaluated, and in the treatment group, the annual increase in vertebral fractures was 0.18 +/- 0.387 and in the control group 0.13 +/- 0.330. New long bone fractures were 7 and 5, respectively. None of the observed differences were statistically significant. In the 1,25(OH)2D3 group, 28% had to reduce the dose because of slight hypercalcaemia. We conclude that 1,25(OH)2D3 as used in this study is not effective in the treatment of osteoporosis.", "Elderly people who have a fracture are at high risk of another. Vitamin D and calcium supplements are often recommended for fracture prevention. We aimed to assess whether vitamin D3 and calcium, either alone or in combination, were effective in prevention of secondary fractures.\n In a factorial-design trial, 5292 people aged 70 years or older (4481 [85%] of whom were women) who were mobile before developing a low-trauma fracture were randomly assigned 800 IU daily oral vitamin D3, 1000 mg calcium, oral vitamin D3 (800 IU per day) combined with calcium (1000 mg per day), or placebo. Participants who were recruited in 21 UK hospitals were followed up for between 24 months and 62 months. Analysis was by intention-to-treat and the primary outcome was new low-energy fractures.\n 698 (13%) of 5292 participants had a new low-trauma fracture, 183 (26%) of which were of the hip. The incidence of new, low-trauma fractures did not differ significantly between participants allocated calcium and those who were not (331 [12.6%] of 2617 vs 367 [13.7%] of 2675; hazard ratio (HR) 0.94 [95% CI 0.81-1.09]); between participants allocated vitamin D3 and those who were not (353 [13.3%] of 2649 vs 345 [13.1%] of 2643; 1.02 [0.88-1.19]); or between those allocated combination treatment and those assigned placebo (165 [12.6%] of 1306 vs 179 [13.4%] of 1332; HR for interaction term 1.01 [0.75-1.36]). The groups did not differ in the incidence of all-new fractures, fractures confirmed by radiography, hip fractures, death, number of falls, or quality of life. By 24 months, 2886 (54.5%) of 5292 were still taking tablets, 451 (8.5%) had died, 58 (1.1%) had withdrawn, and 1897 (35.8%) had stopped taking tablets but were still providing data for at least the main outcomes. Compliance with tablets containing calcium was significantly lower (difference: 9.4% [95% CI 6.6-12.2]), partly because of gastrointestinal symptoms. However, potentially serious adverse events were rare and did not differ between groups.\n The findings do not support routine oral supplementation with calcium and vitamin D3, either alone or in combination, for the prevention of further fractures in previously mobile elderly people.", "To test whether intermittent treatment with slow-release sodium fluoride and continuous calcium citrate supplementation inhibits vertebral fractures without causing fluoride complications.\n A placebo-controlled, randomized trial.\n Outpatient setting of specialty clinics in Dallas and Temple, Texas.\n Slow-release sodium fluoride (25 mg twice daily) in repeated 14-month cycles (12 months on treatment followed by 2 months off treatment) compared with placebo. Both groups took calcium citrate (400 mg calcium twice daily) continuously.\n 110 patients with postmenopausal osteoporosis were randomly assigned to two groups. In the slow-release sodium fluoride group, 48 of 54 patients completed more than 1 cycle of treatment (mean, 2.44 cycles/patient), whereas 51 of 56 patients in the placebo group completed at least 1 cycle (mean, 2.14 cycles/patient) in this interim analysis.\n Vertebral fracture rate and lumbar bone mineral content. Vertebral fractures were quantified from yearly radiographs. Bone mass was determined annually by densitometry.\n In the sodium fluoride group, the mean L2 to L4 bone mineral content increased by 4% to 6% in each cycle and the mean femoral neck bone density increased by 4.1% and 2.1% during the first two cycles, but the radial bone density did not change. The placebo group showed no statistical change in bone mass at any site. Compared with the placebo group, the sodium fluoride group had a lower individual new vertebral fracture rate (0.057/patient cycle compared with 0.204/patient cycle, P = 0.017), a higher fracture-free rate (83.3% compared with 64.7%, P = 0.042), and a lower group fracture rate (0.085/patient cycle compared with 0.239/patient cycle, P = 0.006). The side-effect profile was similar for the two groups; no patient developed microfractures, hip fractures, or blood loss anemia.\n Intermittent slow-release sodium fluoride plus continuous calcium citrate, administered for about 2.5 years, inhibits new vertebral fractures, increases the mean spinal bone mass without decreasing the radial shaft bone density, and is safe to use.", "Low trauma fractures in older people incur enormous physical, social and economic costs. Previous research indicates that an annual intramuscular injection of vitamin D may reduce fracture rates in this group. This strategy requires validation in a population setting.\n Randomized, double-blind, placebo-controlled trial of 300,000 IU intramuscular (i.m.) vitamin D2 (ergocalciferol) injection or matching placebo every autumn over 3 years. 9440 people (4354 men and 5086 women) aged 75 yrs and over were recruited from general practice registers in Wessex, England. Primary outcome measure was all non-vertebral fracture. Secondary outcomes were hip and wrist fractures, and all falls.\n 585 subjects had incident non-spine fractures (hip 110, wrist 116, ankle 37). Hazard ratios (HRs) for fracture in the vitamin D group were: 1.09 [95% confidence interval (CI) 0.93-1.28, P = 0.29] for any first fracture, 1.49 (95% CI 1.02-2.18, P = 0.04) for hip and 1.22 (95% CI 0.85-1.76, P = 0.28) for wrist. There was no effect on falls: HR 0.98 (0.93-1.04). No protective effect was observed in any subgroup when the cohort was stratified by sex, age, previous fracture or mobility.\n An annual i.m. injection of 300,000 IU vitamin D2 is not effective in preventing non-vertebral fractures among elderly men and women resident in the general population.", "Strontium ranelate, a new oral drug shown to reduce vertebral fracture risk in postmenopausal women with osteoporosis, was studied in the Treatment of Peripheral Osteoporosis (TROPOS) study to assess its efficacy and safety in preventing nonvertebral fractures also.\n Strontium ranelate (2 g/d) or placebo were randomly allocated to 5091 postmenopausal women with osteoporosis in a double-blind placebo-controlled 5-yr study with a main statistical analysis over 3 yr of treatment.\n In the entire sample, relative risk (RR) was reduced by 16% for all nonvertebral fractures (P = 0.04), and by 19% for major fragility fractures (hip, wrist, pelvis and sacrum, ribs and sternum, clavicle, humerus) (P = 0.031) in strontium ranelate-treated patients in comparison with the placebo group. Among women at high risk of hip fracture (age > or = 74 yr and femoral neck bone mineral density T score < or = -3, corresponding to -2.4 according to NHANES reference) (n = 1977), the RR reduction for hip fracture was 36% (P = 0.046). RR of vertebral fractures was reduced by 39% (P < 0.001) in the 3640 patients with spinal x-rays and by 45% in the subgroup without prevalent vertebral fracture. Strontium ranelate increased bone mineral density throughout the study, reaching at 3 yr (P < 0.001): +8.2% (femoral neck) and +9.8% (total hip). Incidence of adverse events (AEs) was similar in both groups.\n This study shows that strontium ranelate significantly reduces the risk of all nonvertebral and in a high-risk subgroup, hip fractures over a 3-yr period, and is well tolerated. It confirms that strontium ranelate reduces vertebral fractures. Strontium ranelate offers a safe and effective means of reducing the risk of fracture associated with osteoporosis.", "A high incidence of fractures, particularly of the hip, represents an important problem in patients with Alzheimer's disease (AD), who are prone to falls and may have osteoporosis. We previously showed deficiency of vitamins D and K1 causes reduced bone mineral density (BMD) in female AD patients. The present study was undertaken to address the possibility that treatment with vitamin K2 (menatetrenone; MK-4) may maintain BMD and reduce the incidence of nonvertebral fractures in elderly female patients with AD. In a random and prospective study of AD patients, 100 patients received 45 mg menatetrenone, 1000 IU ergocalciferol and 600 mg calcium daily for 2 years, and the remaining 100 (untreated group) did not. At baseline, patients of both groups showed vitamin D and K1 deficiencies. They also had high serum levels of parathyroid hormone (PTH) and Glu osteocalcin (OC) and low serum ionized calcium, indicating that vitamin D deficiency stimulates compensatory PTH secretion. During the 2-year study period, BMD in the second metacarpals increased by 2.3% in the treated group and decreased by 5.2% in the untreated group (P < 0.0001). Serum levels of vitamin K2 and 25-hydroxyvitamin D increased by 284.9% and 147.9%, respectively, in the treated group. Correspondingly, a significant decrease in Glu OC and PTH were observed, in association with an increased calcium levels, in the treated group. Twenty-two patients in the untreated group sustained nonvertebral fractures (15 with hip fractures, two fractures each at the distal forearm and the proximal femur, each one fracture at the proximal humerus, ribs, and pelvis), and three fractures (2 with hip fractures, one fracture at the proximal femur) occurred among the treated patients (P = 0.0003; odds ratio = 7.5). Treatment with MK-4 and vitamin D2 with calcium supplements increases the BMD in elderly female patients with AD and leads to the prevention of nonvertebral fractures.", "To determine the effect of four monthly vitamin D supplementation on the rate of fractures in men and women aged 65 years and over living in the community.\n Randomised double blind controlled trial of 100 000 IU oral vitamin D3 (cholecalciferol) supplementation or matching placebo every four months over five years.\n 2686 people (2037 men and 649 women) aged 65-85 years living in the general community, recruited from the British doctors register and a general practice register in Suffolk.\n Fracture incidence and total mortality by cause.\n After five years 268 men and women had incident fractures, of whom 147 had fractures in common osteoporotic sites (hip, wrist or forearm, or vertebrae). Relative risks in the vitamin D group compared with the placebo group were 0.78 (95% confidence interval 0.61 to 0.99, P=0.04) for any first fracture and 0.67 (0.48 to 0.93, P=0.02) for first hip, wrist or forearm, or vertebral fracture. 471 participants died. The relative risk for total mortality in the vitamin D group compared with the placebo group was 0.88 (0.74 to 1.06, P=0.18). Findings were consistent in men and women and in doctors and the general practice population.\n Four monthly supplementation with 100 000 IU oral vitamin D may prevent fractures without adverse effects in men and women living in the general community.", "Alendronate sodium reduces fracture risk in postmenopausal women who have vertebral fractures, but its effects on fracture risk have not been studied for women without vertebral fractures.\n To test the hypothesis that 4 years of alendronate would decrease the risk of clinical and vertebral fractures in women who have low bone mineral density (BMD) but no vertebral fractures.\n Randomized, blinded, placebo-controlled trial.\n Eleven community-based clinical research centers.\n Women aged 54 to 81 years with a femoral neck BMD of 0.68 g/cm2 or less (Hologic Inc, Waltham, Mass) but no vertebral fracture; 4432 were randomized to alendronate or placebo and 4272 (96%) completed outcome measurements at the final visit (an average of 4.2 years later).\n All participants reporting calcium intakes of 1000 mg/d or less received a supplement containing 500 mg of calcium and 250 IU of cholecalciferol. Subjects were randomly assigned to either placebo or 5 mg/d of alendronate sodium for 2 years followed by 10 mg/d for the remainder of the trial.\n Clinical fractures confirmed by x-ray reports, new vertebral deformities detected by morphometric measurements on radiographs, and BMD measured by dual x-ray absorptiometry.\n Alendronate increased BMD at all sites studied (P<.001) and reduced clinical fractures from 312 in the placebo group to 272 in the intervention group, but not significantly so (14% reduction; relative hazard [RH], 0.86; 95% confidence interval [CI], 0.73-1.01). Alendronate reduced clinical fractures by 36% in women with baseline osteoporosis at the femoral neck (>2.5 SDs below the normal young adult mean; RH, 0.64; 95% CI, 0.50-0.82; treatment-control difference, 6.5%; number needed to treat [NNT], 15), but there was no significant reduction among those with higher BMD (RH, 1.08; 95% CI, 0.87-1.35). Alendronate decreased the risk of radiographic vertebral fractures by 44% overall (relative risk, 0.56; 95% CI, 0.39-0.80; treatment-control difference, 1.7%; NNT, 60). Alendronate did not increase the risk of gastrointestinal or other adverse effects.\n In women with low BMD but without vertebral fractures, 4 years of alendronate safely increased BMD and decreased the risk of first vertebral deformity. Alendronate significantly reduced the risk of clinical fractures among women with osteoporosis but not among women with higher BMD." ]	At 10 mg per day, both clinically important and statistically significant reductions in vertebral, non-vertebral, hip and wrist fractures were observed for secondary prevention ('gold' level evidence, www.cochranemsk.org). We found no statistically significant results for primary prevention, with the exception of vertebral fractures, for which the reduction was clinically important ('gold' level evidence).
CD004082	[ "12357146", "15242867", "22014804", "10781452", "17522511", "20156348", "7535996", "16155038", "11881887", "14553868", "16888706", "20613538", "21873370", "10213716", "9361539", "7907668", "2222242", "7580360", "19142552", "10929164", "16356219", "7519132", "12595838", "12816266", "10993856", "9339929", "7517058", "16714768", "20380111", "11902288" ]	[ "Goal-directed intraoperative fluid administration reduces length of hospital stay after major surgery.", "Randomised controlled trial assessing the impact of a nurse delivered, flow monitored protocol for optimisation of circulatory status after cardiac surgery.", "A double-blind randomized controlled clinical trial to assess the effect of Doppler optimized intraoperative fluid management on outcome following radical cystectomy.", "A prospective, randomized study of goal-oriented hemodynamic therapy in cardiac surgical patients.", "A prospective randomized controlled trial of multimodal perioperative management protocol in patients undergoing elective colorectal resection for cancer.", "Goal-directed intraoperative therapy based on autocalibrated arterial pressure waveform analysis reduces hospital stay in high-risk surgical patients: a randomized, controlled trial.", "Perioperative plasma volume expansion reduces the incidence of gut mucosal hypoperfusion during cardiac surgery.", "Intraoperative oesophageal Doppler guided fluid management shortens postoperative hospital stay after major bowel surgery.", "Randomized controlled trial to investigate influence of the fluid challenge on duration of hospital stay and perioperative morbidity in patients with hip fractures.", "Implementation of an evidence-based guideline to reduce duration of intravenous antibiotic therapy and length of stay for patients hospitalized with community-acquired pneumonia: a randomized controlled trial.", "Randomized clinical trial assessing the effect of Doppler-optimized fluid management on outcome after elective colorectal resection.", "A randomized controlled trial comparing an intraoperative goal-directed strategy with routine clinical practice in patients undergoing peripheral arterial surgery.", "Randomized controlled trial of intraoperative goal-directed fluid therapy in aerobically fit and unfit patients having major colorectal surgery.", "Reducing the risk of major elective surgery: randomised controlled trial of preoperative optimisation of oxygen delivery.", "Intraoperative intravascular volume optimisation and length of hospital stay after repair of proximal femoral fracture: randomised controlled trial.", "A randomized clinical trial of the effect of deliberate perioperative increase of oxygen delivery on mortality in high-risk surgical patients.", "Failure of surgery to improve outcome in hypertensive putaminal hemorrhage. A prospective randomized trial.", "Intraoperative antifibrinolysis and blood-saving techniques in cardiac surgery. Prospective trial of 3 antifibrinolytic drugs.", "Intensive perioperative glucose control does not improve outcomes of patients submitted to open-heart surgery: a randomized controlled trial.", "Effect of a preoperative intervention on preoperative and postoperative outcomes in low-risk patients awaiting elective coronary artery bypass graft surgery. A randomized, controlled trial.", "Early goal-directed therapy after major surgery reduces complications and duration of hospital stay. A randomised, controlled trial [ISRCTN38797445].", "Randomized study of aprotinin and DDAVP to reduce postoperative bleeding after cardiopulmonary bypass surgery.", "Double-blind, placebo-controlled, randomized trial of prophylactic metoprolol for reduction of hospital length of stay after heart surgery: the beta-Blocker Length Of Stay (BLOS) study.", "The efficacy and safety of aprotinin for hemostasis during intracranial surgery.", "Randomized controlled study investigating the effect of biatrial pacing in prevention of atrial fibrillation after coronary artery bypass grafting.", "Routine pulmonary artery catheterization does not reduce morbidity and mortality of elective vascular surgery: results of a prospective, randomized trial.", "[Use of high doses of aprotinin in cardiac surgery].", "Pulmonary-artery versus central venous catheter to guide treatment of acute lung injury.", "Proton pump inhibitors after endoscopic hemostasis in patients with peptic ulcer bleeding.", "Effect of an education program on decreasing catheter-related bloodstream infections in the surgical intensive care unit." ]	[ "Intraoperative hypovolemia is common and is a potential cause of organ dysfunction, increased postoperative morbidity, length of hospital stay, and death. The objective of this prospective, randomized study was to assess the effect of goal-directed intraoperative fluid administration on length of postoperative hospital stay.\n One hundred patients who were to undergo major elective surgery with an anticipated blood loss greater than 500 ml were randomly assigned to a control group (n = 50) that received standard intraoperative care or to a protocol group (n = 50) that, in addition, received intraoperative plasma volume expansion guided by the esophageal Doppler monitor to maintain maximal stroke volume. Length of postoperative hospital stay and postoperative surgical morbidity were assessed.\n Groups were similar with respect to demographics, surgical procedures, and baseline hemodynamic variables. The protocol group had a significantly higher stroke volume and cardiac output at the end of surgery compared with the control group. Patients in the protocol group had a shorter duration of hospital stay compared with the control group: 5 +/- 3 versus 7 +/- 3 days (mean +/- SD), with a median of 6 versus 7 days, respectively ( = 0.03). These patients also tolerated oral intake of solid food earlier than the control group: 3 +/- 0.5 versus 4.7 +/- 0.5 days (mean +/- SD), with a median of 3 versus 5 days, respectively ( = 0.01).\n Goal-directed intraoperative fluid administration results in earlier return to bowel function, lower incidence of postoperative nausea and vomiting, and decrease in length of postoperative hospital stay.", "To assess whether a nurse led, flow monitored protocol for optimising circulatory status in patients after cardiac surgery reduces complications and shortens stay in intensive care and hospital.\n Randomised controlled trial.\n Intensive care unit and cardiothoracic unit of a university teaching hospital.\n 174 patients who underwent cardiac surgery between April 2000 and January 2003.\n Patients were allocated to conventional haemodynamic management or to an algorithm guided by oesophageal Doppler flowmetry to maintain a stroke index above 35 ml/m2.\n 26 control patients had postoperative complications (two deaths) compared with 17 (four deaths) protocol patients (P = 0.08). Duration of hospital stay in the protocol group was significantly reduced from a median of nine (interquartile range 7-12) days to seven (7-10) days (P = 0.02). The mean duration of hospital stay was reduced from 13.9 to 11.4 days, a saving in hospital bed days of 18% (95% confidence interval -12% to 47%). Usage of intensive care beds was reduced by 23% (-8% to 59%).\n A nurse delivered protocol for optimising circulatory status in the early postoperative period after cardiac surgery may significantly shorten hospital stay.", "Cardiovascular optimization via esophageal Doppler can minimize gastrointestinal hypoperfusion, reducing the risk of multiple organ dysfunction and postoperative complications during major surgery. We assessed the effect of esophageal Doppler guided cardiovascular optimization in patients undergoing radical cystectomy.\n We conducted a prospective, randomized, double-blind controlled trial at a United Kingdom teaching hospital between 2006 and 2009. A total of 66 patients were randomized to a control arm (34) and an intervention arm (32). The control group received standard intraoperative fluids. The intervention group received (additional) Doppler guided fluid. Primary outcomes were markers of gastrointestinal morbidity such as ileus, flatus and bowel opening. Secondary outcomes were postoperative nausea and vomiting, wound infection and operative intravenous fluid volumes (total and hourly).\n There were significant reductions in the control and intervention arms in the incidence of ileus (18 vs 7, p <0.001), flatus (5.36 vs 3.55 days, p <0.01) and bowel opening (9.79 vs 6.53 days, p = 0.02), respectively. Nausea and vomiting were significantly reduced in the study group at 24 and 48 hours postoperatively (11 vs 3, p <0.01 and 13 vs 1, p <0.0001). Wound infection rates were significantly reduced (8 vs 1 superficial, p <0.01 and 10 vs 2 combined, p <0.01). Study patients received significantly higher volumes (ml/kg per minute) of intravenous fluid (0.19 vs 0.23, p <0.01) related to a significantly higher volume (ml/kg) in the first hour of surgery (14.1 vs 21.0, p = 0.0001).\n Cardiovascular optimization using esophageal Doppler significantly improved postoperative markers of gastrointestinal function.\n Copyright Â© 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.", "Organ dysfunction and multiple organ failure are the main causes of prolonged hospital stay after cardiac surgery, which increases resource use and health care costs. Increased levels of oxygen delivery and consumption are associated with improved outcome in different groups of postoperative patients. Cardiac surgical patients are at risk of inadequate perioperative oxygen delivery caused by extracorporeal circulation and limited cardiovascular reserves. The purpose of our study was to test whether increasing oxygen delivery immediately after cardiac surgery would shorten hospital and intensive care unit (ICU) stay. Four hundred three elective cardiac surgical patients were enrolled in the study and randomly assigned to either the control or the protocol group. Goals of the protocol group were to maintain SvO(2) >70% and lactate concentration < or =2.0 mmol/L from admission to the ICU and up to 8 h thereafter. Hemodynamics, oxygen transport data, and organ dysfunctions were recorded. The median hospital stay was shorter in the protocol group (6 vs 7 days, P < 0.05), and patients were discharged faster from the hospital than those in the control group (P < 0.05). Discharge from the ICU was similar between groups (P = 0. 8). Morbidity was less frequent at the time of hospital discharge in the protocol group (1.1% vs 6.1%, P < 0.01). Increasing oxygen delivery to achieve normal SvO(2) values and lactate concentration during the immediate postoperative period after cardiac surgery can shorten the length of hospital stay. Implications: Health care economics has challenged clinicians to reduce costs and improve resource use in cardiac surgery and anesthesia in a patient population increasing in age and in severity of disease. Optimizing cardiovascular function to maintain adequate oxygen delivery during the immediate postoperative period after cardiac surgery can decrease morbidity and reduce length of hospital stay.", "A prospective randomized controlled trial (RCT) of multimodal perioperative management protocol in patients undergoing elective colorectal resection for cancer.\n This study evaluates the use of a multimodal package in colorectal cancer surgery in the context of an RCT.\n Patients for elective resection for colorectal cancer were offered trial entry. Participants were stratified by sex and requirement for a total mesorectal excision and centrally randomized. Multimodal patients received intravenous fluid restriction, unrestricted oral intake with prokinetic agents, early ambulation, and fixed regimen epidural analgesia. Control patients received intravenous fluids to prevent oliguria, restricted oral intake until return of bowel motility, and weaning regimen epidural analgesia. Adherence to both regimens was reinforced using a daily checklist and protocol guidance sheets. Discharge decision was made using pre-agreed criteria. The primary endpoint was postoperative stay, and achievement of independence milestones. Secondary endpoints were postoperative complications, readmission rates, and mortality. Analysis was by intention to treat.\n Seventy patients were recruited. Approximately one fourth underwent TME. Median ages were similar (69.3 vs. 73.0 years). The median stay was significantly reduced in the multimodal group (5 vs. 7 days; P < 0.001, Mann-Whitney U test). Patients in the control arm were 2.5 times as likely to require a postoperative stay of more than 5 days. Patients in the multimodal group had less cardiorespiratory and anastomotic complications but more readmissions. There were 2 deaths, both controls.\n This RCT provides level 1b evidence that a multimodal management protocol can significantly reduce postoperative stay following colorectal cancer surgery. Morbidity and mortality are not increased.", "Several studies have shown that goal-directed hemodynamic and fluid optimization may result in improved outcome. However, the methods used were either invasive or had other limitations. The aim of this study was to perform intraoperative goal-directed therapy with a minimally invasive, easy to use device (FloTrac/Vigileo), and to evaluate possible improvements in patient outcome determined by the duration of hospital stay and the incidence of complications compared to a standard management protocol.\n In this randomized, controlled trial 60 high-risk patients scheduled for major abdominal surgery were included. Patients were allocated into either an enhanced hemodynamic monitoring group using a cardiac index based intraoperative optimization protocol (FloTrac/Vigileo device, GDT-group, n = 30) or a standard management group (Control-group, n = 30), based on standard monitoring data.\n The median duration of hospital stay was significantly reduced in the GDT-group with 15 (12 - 17.75) days versus 19 (14 - 23.5) days (P = 0.006) and fewer patients developed complications than in the Control-group [6 patients (20%) versus 15 patients (50%), P = 0.03]. The total number of complications was reduced in the GDT-group (17 versus 49 complications, P = 0.001).\n In high-risk patients undergoing major abdominal surgery, implementation of an intraoperative goal-directed hemodynamic optimization protocol using the FloTrac/Vigileo device was associated with a reduced length of hospital stay and a lower incidence of complications compared to a standard management protocol.\n Clinical trial registration information: Unique identifier: NCT00549419.", "To test the hypothesis that perioperative plasma volume expansion would preserve gut mucosal perfusion during elective cardiac surgery.\n Prospective randomized open study.\n Teaching hospital.\n Sixty American Society of Anesthesiology grade III patients with a preoperative left ventricular ejection fraction of 50% or greater undergoing elective cardiac surgery.\n Patients were allocated randomly to a control or protocol group. The control group was treated according to standard practices. After induction of general anesthesia, the protocol group received, in addition, 200-mL boluses of a 6% hydroxyethyl starch solution to obtain a maximum stroke volume. This procedure was repeated every 15 minutes until the end of surgery, except when the patient underwent cardiopulmonary bypass.\n Cardiac stroke volume was estimated by an esophageal Doppler system, and gastric mucosal perfusion was measured by tonometric assessment of gastric intramucosal pH in all patients. Patients were followed up postoperatively until discharge from the hospital or death. The incidence of gut mucosal hypoperfusion (gastric intramucosal pH < 7.32) at the end of surgery was reduced in the protocol group (7% vs 56%) (P < .001), as were the number of patients in whom major complications developed (0 vs 6) (P = .01), mean number of days spent in the hospital (6.4 [range, 5 to 9] vs 10.1 [range, 5 to 48]) (P = .011), and mean number of days spent in the intensive care unit (1 [range, 1 to 1] vs 1.7 [range 1 to 11] days) (P = .023).\n Perioperative plasma volume expansion with colloid during cardiac surgery, guided by esophageal Doppler measurement of cardiac stroke volume, reduced the incidence of gut mucosal hypoperfusion. This group of patients also had an improved outcome when compared with controls.", "Occult hypovolaemia is a key factor in the aetiology of postoperative morbidity and may not be detected by routine heart rate and arterial pressure measurements. Intraoperative gut hypoperfusion during major surgery is associated with increased morbidity and postoperative hospital stay. We assessed whether using intraoperative oesophageal Doppler guided fluid management to minimize hypovolaemia would reduce postoperative hospital stay and the time before return of gut function after colorectal surgery.\n This single centre, blinded, prospective controlled trial randomized 128 consecutive consenting patients undergoing colorectal resection to oesophageal Doppler guided or central venous pressure (CVP)-based (conventional) intraoperative fluid management. The intervention group patients followed a dynamic oesophageal Doppler guided fluid protocol whereas control patients were managed using routine cardiovascular monitoring aiming for a CVP between 12 and 15 mm Hg.\n The median postoperative stay in the Doppler guided fluid group was 10 vs 11.5 days in the control group P<0.05. The median time to resuming full diet in the Doppler guided fluid group was 6 vs 7 for controls P<0.001. Doppler patients achieved significantly higher cardiac output, stroke volume, and oxygen delivery. Twenty-nine (45.3%) control patients suffered gastrointestinal morbidity compared with nine (14.1%) in the Doppler guided fluid group P<0.001, overall morbidity was also significantly higher in the control group P=0.05.\n Intraoperative oesophageal Doppler guided fluid management was associated with a 1.5-day median reduction in postoperative hospital stay. Patients recovered gut function significantly faster and suffered significantly less gastrointestinal and overall morbidity.", "A prospective, randomized controlled trial comparing conventional intraoperative fluid management with two differing methods of invasive haemodynamic monitoring to optimize intraoperative fluid therapy, in patients undergoing proximal femoral fracture repair under general anaesthesia.\n Ninety patients randomized to three groups; conventional intraoperative fluid management (Gp CON, n=29), and two groups receiving additional repeated colloid fluid challenges guided by central venous pressure (Gp CVP, n=31) or oesophageal Doppler ultrasonography (Gp DOP, n=30). Primary outcome measures were time to medical fitness to discharge, hospital stay and postoperative morbidity.\n The fluid challenge resulted in significantly greater perioperative changes in central venous pressure between Gp CVP and Gp CON (mean 5 (95% confidence interval 3-7) mm Hg) (P<0.0001). Important perioperative changes were also shown in Gp DOP with increases of 49.4 ms (19.7-79.1 ms) in the corrected flow time, 13.5 ml (7.4-19.6 ml) in stroke volume, and 0.9 (0.49-1.39) litre min(-1) in cardiac output. As a result, fewer patients in Gp CVP and Gp DOP experienced severe intraoperative hypotension (Gp CON 28% (8/29), Gp CVP 9% (3/31), Gp DOP 7% (2/30), P=0.048 (chi-squared, 2 degrees of freedom (df). No differences were seen between the three groups when major morbidity and mortality were combined, P=0.24 (chi-squared, 2 df). Postoperative recovery for survivors, as defined by time to be deemed medically fit for discharge, was significantly faster, in comparison with Gp CON, in both the Gp CVP (10 vs 14 (95% confidence interval 8-12 vs 12-17) days, P=0.008 (t-test)), and Gp DOP (8 vs 14 (95% confidence interval 6-12 vs 12-17) days, P=0.023 (t-test). There were no significant differences between groups, for survivors, with respect to acute orthopaedic hospital and total hospital stay.\n Invasive intraoperative haemodynamic monitoring with fluid challenges during repair of femoral fracture under general anaesthetic shortens time to being medically fit for discharge.", "Patients with pneumonia often remain hospitalized after they are stable clinically, and the duration of intravenous antibiotic therapy is a rate-limiting step for discharge. The purpose of this study was to determine whether implementation of an evidence-based guideline would reduce the duration of intravenous antibiotic therapy and length of stay for patients hospitalized with pneumonia.\n In a seven-site, cluster randomized clinical trial, we enrolled 325 control and 283 intervention patients who were admitted by one of 116 physician groups. Within site, physician groups were assigned randomly to receive a practice guideline alone (control arm) or a practice guideline that was implemented using a multifaceted strategy (intervention arm). The effectiveness of guideline implementation was measured by the duration of intravenous antibiotic therapy and length of stay; differences in the rates of discontinuation and hospital discharge were assessed with proportional hazards models. Medical outcomes were assessed at 30 days.\n Intravenous antibiotic therapy was discontinued somewhat more quickly in the intervention group (hazard ratio [HR] =1.23; 95% confidence interval [CI]: 1.00 to 1.52; P = 0.06) than in the control group. Intervention patients were discharged more quickly, but the difference was not statistically significant (HR = 1.16; 95% CI: 0.97 to 1.38; P = 0.11). Fewer intervention (55% [157/283]) than control (63% [206/325]) patients had medical complications during the index hospitalization (P = 0.04), with no differences in other medical outcomes, including mortality, rehospitalization, and return to usual activities, between treatment arms.\n The multifaceted guideline implementation strategy resulted in a slight reduction in the duration of intravenous antibiotic therapy and a nonsignificant reduction in length of stay, without affecting patient outcomes.", "Protocolized fluid administration using oesophageal Doppler monitoring may improve the postoperative outcome in patients undergoing surgery.\n A total of 108 patients undergoing elective colorectal resection were recruited into a double-blind prospective randomized controlled trial. An oesophageal Doppler probe was placed in all patients. The control group received perioperative fluid at the discretion of the anaesthetist, whereas the intervention group received additional colloid boluses based on Doppler assessment. Primary outcome was length of postoperative hospital stay. Secondary outcomes were morbidity, return of gastrointestinal function and cytokine markers of the systemic inflammatory response. Standard preoperative and postoperative management was used in all patients.\n Demographic and surgical details were similar in the two groups. Aortic flow time, stroke volume, cardiac output and cardiac index during the intraoperative period were higher in the intervention group (P<0.050). The intervention group had a reduced postoperative hospital stay (7 versus 9 days in the control group; P=0.005), fewer intermediate or major postoperative complications (2 versus 15 percent; P=0.043) and tolerated diet earlier (2 versus 4 days; P=0.029). There was a reduced rise in perioperative level of the cytokine interleukin 6 in the intervention group (P=0.039).\n A protocol-based fluid optimization programme using intraoperative oesophageal Doppler monitoring leads to a shorter hospital stay and decreased morbidity in patients undergoing elective colorectal resection.\n Copyright (c) 2006 British Journal of Surgery Society Ltd.", "We hypothesized that, in vascular surgery patients, the application of a goal-directed strategy based on a pulse contour-derived cardiac index would be associated with a better haemodynamic status than the application of routine perioperative care and that the amount of fluid and/or inotropes required in such a goal-directed therapy depended on the general anaesthetic technique used.\n Patients undergoing peripheral arterial bypass grafting were randomly assigned to three groups. In group 1, haemodynamic management was performed according to routine clinical practice. In the two other groups (groups 2 and 3) a goal-directed therapy was applied aiming to maintain the pulse contour-derived cardiac index above 2.5 l m min. Patients in groups 1 and 2 received sevoflurane-based anaesthesia and patients in group 3 propofol-based anaesthesia. Haemodynamic variables, amount of fluid and administration of inotropes were assessed at different time intervals.\n The amount of fluid administered was not significantly different between the groups. Two patients in group 1, 13 patients in group 2 and 12 patients in group 3 were treated with dobutamine (P < 0.001). None of the patients anaesthetized with sevoflurane (groups 1 and 2) experienced postoperative cardiovascular complications, whereas four patients in the total intravenous group (group 3) experienced major postoperative cardiovascular complications (P = 0.005).\n In the conditions of the present study, the application of a goal-directed therapy aiming to maintain the cardiac index above 2.5 l min m did not result in a higher tissue oxygen delivery than when applying the standard haemodynamic strategy nor did it depend on the anaesthetic technique used.", "Intraoperative fluid therapy regimens using oesophageal Doppler monitoring (ODM) to optimize stroke volume (SV) (goal-directed fluid therapy, GDT) have been associated with a reduction in length of stay (LOS) and complication rates after major surgery. We hypothesized that intraoperative GDT would reduce the time to surgical readiness for discharge (RfD) of patients having major elective colorectal surgery but that this effect might be less marked in aerobically fit patients.\n In this double-blinded controlled trial, 179 patients undergoing major open or laparoscopic colorectal surgery were characterized as aerobically 'fit' (n=123) or 'unfit' (n=56) on the basis of their performance during a cardiopulmonary exercise test. Within these fitness strata, patients were randomized to receive a standard fluid regimen with or without ODM-guided intraoperative GDT.\n GDT patients received an average of 1360 ml of additional intraoperative colloid. The mean cardiac index and SV at skin closure were significantly higher in the GDT group than in controls. Times to RfD and LOS were longer in GDT than control patients but did not reach statistical significance (median 6.8 vs 4.9 days, P=0.09, and median 8.8 vs 6.7 days, P=0.09, respectively). Fit GDT patients had an increased RfD (median 7.0 vs 4.7 days; P=0.01) and LOS (median 8.8 vs 6.0 days; P=0.01) compared with controls.\n Intraoperative SV optimization conferred no additional benefit over standard fluid therapy. In an aerobically fit subgroup of patients, GDT was associated with detrimental effects on the primary outcome.\n UK NIHR CRN 7285, ISRCTN 14680495. http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=7285.", "To determine whether preoperative optimisation of oxygen delivery improves outcome after major elective surgery, and to determine whether the inotropes, adrenaline and dopexamine, used to enhance oxygen delivery influence outcome.\n Randomised controlled trial with double blinding between inotrope groups. Setting: York District Hospital, England.\n 138 patients undergoing major elective surgery who were at risk of developing postoperative complications either because of the surgery or the presence of coexistent medical conditions. Interventions: Patients were randomised into three groups. Two groups received invasive haemodynamic monitoring, fluid, and either adrenaline or dopexamine to increase oxygen delivery. Inotropic support was continued during surgery and for at least 12 hours afterwards. The third group (control) received routine perioperative care.\n Hospital mortality and morbidity.\n Overall, 3/92 (3%) preoptimised patients died compared with 8/46 controls (17%) (P=0.007). There were no differences in mortality between the treatment groups, but 14/46 (30%) patients in the dopexamine group developed complications compared with 24/46 (52%) patients in the adrenaline group (difference 22%, 95% confidence interval 2% to 41%) and 28 patients (61%) in the control group (31%, 11% to 50%). The use of dopexamine was associated with a decreased length of stay in hospital.\n Routine preoperative optimisation of patients undergoing major elective surgery would be a significant and cost effective improvement in perioperative care.", "To assess whether intraoperative intravascular volume optimisation improves outcome and shortens hospital stay after repair of proximal femoral fracture.\n Prospective, randomised controlled trial comparing conventional intraoperative fluid management with repeated colloid fluid challenges monitored by oesophageal Doppler ultrasonography to maintain maximal stroke volume throughout the operative period.\n Teaching hospital, London.\n 40 patients undergoing repair of proximal femoral fracture under general anaesthesia.\n Patients were randomly assigned to receive either conventional intraoperative fluid management (control patients) or additional repeated colloid fluid challenges with oesophageal Doppler ultrasonography used to maintain maximal stroke volume throughout the operative period (protocol patients).\n Time declared medically fit for hospital discharge, duration of hospital stay (in acute bed; in acute plus long stay bed), mortality, perioperative haemodynamic changes.\n Intraoperative intravascular fluid loading produced significantly greater changes in stroke volume (median 15 ml (95% confidence interval 10 to 21 ml)) and cardiac output (1.2 l/min (0.1 to 2.3 l/min)) than in the conventionally managed group (-5 ml (-10 to 1 ml) and -0.4 l/min (-1.0 to 0.2 l/min)) (P < 0.001 and P < 0.05, respectively). One protocol patient and two control patients died in hospital. In the survivors, postoperative recovery was significantly faster in the protocol patients, with shorter times to being declared medically fit for discharge (median 10 (9 to 15) days v 15 (11 to 40) days, P < 0.05) and a 39% reduction in hospital stay (12 (8 to 13) days v 20 (10 to 61) days, P < 0.05).\n Proximal femoral fracture repair constitutes surgery in a high risk population. Intraoperative intravascular volume loading to optimal stroke volume resulted in a more rapid postoperative recovery and a significantly reduced hospital stay.", "To assess the effect of deliberate perioperative increase in oxygen delivery on mortality and morbidity in patients who are at high risk of both following surgery.\n Prospective, randomized clinical trial.\n A teaching hospital general intensive care unit, London, England.\n A total of 107 surgical patients, who were assessed as high risk from previously identified criteria, were studied during an 18-month period.\n Patients were randomly assigned to a control group (n = 54) that received best standard perioperative care, or to a protocol group (n = 53) that, in addition, had deliberate increase of oxygen delivery index to greater than 600 mL/min per square meter by use of dopexamine hydrochloride infusion.\n Mortality and complications were assessed to 28 days postoperatively.\n Groups were similar with respect to demographics, admission criteria, operation type, and admission hemodynamic variables. Groups were treated similarly to maintain blood pressure, arterial saturation, hemoglobin concentration, and pulmonary artery occlusion pressure; however, once additional treatment with dopexamine hydrochloride had been given, the protocol group had significantly higher oxygen delivery preoperatively (median, 597 vs 399 mL/min per square meter; P < .001) and postoperatively (P < .001). Results indicate a 75% reduction in mortality (5.7% vs 22.2%; P = .015) and a halving of the mean (+/- SEM) number of complications per patient (0.68 [+/- 0.16] vs 1.35 [+/- 0.20]; P = .008) in patients randomized to the protocol group.\n Perioperative increase of oxygen delivery with dopexamine hydrochloride significantly reduces mortality and morbidity in high-risk surgical patients.", "Hypertensive putaminal hemorrhage remains a major cause of hemorrhagic stroke carrying extremely high morbidity. Considerable controversy remains regarding the optimal form of therapy. Between 1983 and 1989 we conducted a prospective randomized trial with three treatment strategies: best medical management, best medical management plus intracranial pressure monitoring, and surgical evacuation. Only patients with significant deficit harboring a putaminal hematoma at least 3.0 cm in diameter were entered. The study was interrupted after 21 patients had been studied (9, best medical management; 4, intracranial pressure monitoring; and 8, surgical evacuation). No differences were found among groups for age, admission blood pressure, and time interval between onset of symptoms and arrival at hospital. None of the subjects were capable of returning to prestroke activity. Fifteen (71%) died or remained vegetative at 6 months, and only 4 (19%) were capable of independent life at home. Of the 9 patients in the best medical management arm, 7 were dead or vegetative. In the surgical group, 4 patients died and only 2 were capable of independent life. These results suggest that current medical and neurosurgical therapies remain ineffective in preventing the devastating neurologic consequences of hypertensive putaminal hemorrhage.", "Sixty consecutive patients undergoing elective open-heart surgery were prospectively enrolled in a study to compare the efficacy of 3 different antifibrinolytic drugs to reduce postoperative bleeding and to reduce homologous blood requirements in combination with blood-saving techniques and restrictive indications for blood transfusion. The patients were randomized to 1 of 4 intraoperative treatment regimens: 1) control (no antifibrinolytic therapy); 2) epsilon-aminocaproic acid (10 g IV at induction of anesthesia, followed by infusion of 2 g/h for 5 hours); 3) tranexamic acid (10 mg/kg IV within 30 minutes after induction of anesthesia, followed by infusion of 1 mg/kg per hour for 10 hours); or 4) high-dose aprotinin (2 million KIU IV at induction of anesthesia and 2 million KIU added to the extracorporeal circuit, followed by infusion of 500 thousand KIU/h during surgery). Hemoconcentration and reinfusion of blood drained from the operative field and the extracorporeal circuit after operation were used in all patients. Indications for blood transfusion were hypotension, tachycardia, or both, with hemoglobin values < 8.5 g/dL; or severe anemia with hemoglobin values < 7 g/dL. Compared with the blood loss in the control group, patients receiving aprotinin and epsilon-aminocaproic acid showed significantly less postoperative blood loss at 1 hour (control, 128 +/- 94 mL; aprotinin, 54 +/- 47 mL, p = 0.01; and epsilon-aminocaproic acid, 69 +/- 35 mL, p = 0.03); this trend continued at 24 hours after operation (control, 724 +/- 280 mL; aprotinin, 344 +/- 106 mL, p < 0.0001; and epsilon-aminocaproic acid, 509 +/- 148 mL, p = 0.01). Aprotinin was significantly more efficient than epsilon-aminocaproic acid (p=0.002). Tranexamic acid did not have a statistically significant effect on blood loss. Homologous blood requirements were not significantly different among the groups; postoperative hematologic values and coagulation times were also comparable. Despite the efficacy of aprotinin and epsilon-aminocaproic acid shown in the present study, the blood requirements were not significantly different from those that are found when transfusions are restricted, autotransfusions are used, and blood from the operative field and extracorporeal circuit is concentrated and reinfused. Therefore, intraoperative antifibrinolysis may not be indicated in routine cardiac surgery when other blood-saving techniques are adopted.", "The objective of this study was to investigate the relationship between different target levels of glucose and the clinical outcomes of patients undergoing cardiac surgery with cardiopulmonary bypass.\n We designed a prospective study in a university hospital where 109 consecutive patients were enrolled during a six-month period. All patients were scheduled for open-heart surgery requiring cardiopulmonary bypass. Patients were randomly allocated into two groups. One group consisted of 55 patients and had a target glucose level of 80-130 mg/dl, while the other contained 54 patients and had a target glucose level of 160-200 mg/dl. These parameters were controlled during surgery and for 36 hours after surgery in the intensive care unit. Primary outcomes were clinical outcomes, including time of mechanical ventilation, length of stay in the intensive care unit, infection, hypoglycemia, renal or neurological dysfunction, blood transfusion and length of stay in the hospital. The secondary outcome was a combined end-point (mortality at 30 days, infection or length of stay in the intensive care unit of more than 3 days). A p-value of <0.05 was considered significant.\n The anthropometric and clinical characteristics of the patients from each group were similar, except for weight and body mass index. The mean glucose level during the protocol period was 126.69 mg/dl in the treated group and 168.21 mg/dl in the control group (p<0.0016). There were no differences between groups regarding clinical outcomes, including the duration of mechanical ventilation, length of stay in the intensive care unit, blood transfusion, postoperative infection, hypoglycemic event, neurological dysfunction or 30-day mortality (p>0.05).\n In 109 patients undergoing cardiac surgery with cardiopulmonary bypass, both protocols of glycemic control in an intraoperative setting and in the intensive care unit were found to be safe, easily achieved and not to differentially affect clinical outcomes.", "In publicly funded health care systems, a waiting period for such services as coronary artery bypass graft surgery (CABG) is common. The possibility of using the waiting period to improve patient outcomes should be investigated.\n To examine the effect of a multidimensional preoperative intervention on presurgery and postsurgery outcomes in low-risk patients awaiting elective CABG.\n Randomized, controlled trial.\n A regional cardiovascular surgery center in a tertiary care hospital, southwestern Ontario, Canada.\n 249 patients on a waiting list for elective CABG whose surgeries were scheduled for a minimum of 10 weeks from the time of study recruitment.\n During the waiting period, the treatment group received exercise training twice per week, education and reinforcement, and monthly nurse-initiated telephone calls. After surgery, participation in a cardiac rehabilitation program was offered to all patients.\n Postoperative length of stay was the primary outcome. Secondary outcomes were exercise performance, general health-related quality of life, social support, anxiety, and utilization of health care services.\n Length of stay differed significantly between groups. Patients who received the preoperative intervention spent 1 less day [95% CI, 0.0 to 1.0 day] in the hospital overall (P = 0.002) and less time in the intensive care unit (median, 2.1 hours [CI, -1.2 to 16 hours]; P = 0.001). During the waiting period, patients in the intervention group had a better quality of life than controls. Improved quality of life continued up to 6 months after surgery. Mortality rates did not differ.\n The waiting period for elective procedures, such as CABG, may be used to enhance in-hospital and early-phase recovery, improving patients' functional abilities and quality of life while reducing their hospital stay.", "Goal-directed therapy (GDT) has been shown to improve outcome when commenced before surgery. This requires pre-operative admission to the intensive care unit (ICU). In cardiac surgery, GDT has proved effective when commenced after surgery. The aim of this study was to evaluate the effect of post-operative GDT on the incidence of complications and duration of hospital stay in patients undergoing general surgery.\n This was a randomised controlled trial with concealed allocation. High-risk general surgical patients were allocated to post-operative GDT to attain an oxygen delivery index of 600 ml min(-1) m(-2) or to conventional management. Cardiac output was measured by lithium indicator dilution and pulse power analysis. Patients were followed up for 60 days.\n Sixty-two patients were randomised to GDT and 60 patients to control treatment. The GDT group received more intravenous colloid (1,907 SD +/- 878 ml versus 1,204 SD +/- 898 ml; p < 0.0001) and dopexamine (55 patients (89%) versus 1 patient (2%); p < 0.0001). Fewer GDT patients developed complications (27 patients (44%) versus 41 patients (68%); p = 0.003, relative risk 0.63; 95% confidence intervals 0.46 to 0.87). The number of complications per patient was also reduced (0.7 SD +/- 0.9 per patient versus 1.5 SD +/- 1.5 per patient; p = 0.002). The median duration of hospital stay in the GDT group was significantly reduced (11 days (IQR 7 to 15) versus 14 days (IQR 11 to 27); p = 0.001). There was no significant difference in mortality (seven patients (11.3%) versus nine patients (15%); p = 0.59).\n Post-operative GDT is associated with reductions in post-operative complications and duration of hospital stay. The beneficial effects of GDT may be achieved while avoiding the difficulties of pre-operative ICU admission.", "Patients on cardiopulmonary bypass (CPB) have an increased susceptibility to postoperative bleeding. Previous reports using desmopressin acetate (DDAVP) for the prevention of postoperative bleeding have given contradictory results, whereas the protease inhibitor aprotinin has been shown to reduce blood loss after this type of surgery. This randomized study was performed to assess the efficacy of DDAVP versus aprotinin in the prevention of bleeding after CPB.\n One hundred nine of 122 eligible patients were randomized to four different groups: Group A (n = 28) received aprotinin starting with a bolus of 2 x 10(6) KIU followed by a continuous infusion of 0.5 x 10(6) KIU/h until the end of surgery; group B (n = 25) received of DDAVP 0.3 micrograms/kg i.v. on completion of CPB; group C (n = 28) received two doses of DDAVP, the first as in group B and an additional dose 6 hours after surgery; group D (n = 28) received no treatment. There was a marked reduction of postoperative blood loss either at 12 hours (P < .01) or 72 hours (P < .02) in the aprotinin group compared with all other groups, whereas no significant effect was observed in either of the two DDAVP regimens. A significant reduction in the amount of blood used was observed only in the aprotinin group (P < .01). Of the plasma fibrinolytic components assayed, there was a significant reduction of the fibrin degradation product generation in the aprotinin group (P < .001), whereas a significant systemic hyperfibrinolysis was observed in both DDAVP-treated groups and the control group. No side effects related to the study drugs were observed in any patient.\n Aprotinin inhibited fibrinolysis; this correlated with a significant reduction of postoperative blood loss and need for blood replacement after CPB. Neither one nor two doses of DDAVP had a beneficial effect. Aprotinin offers a better alternative than DDAVP in the prevention of bleeding after CPB.", "Atrial fibrillation (AF) is a common complication of heart surgery. Previous studies have shown that there is an association between postoperative AF and prolongation of hospital length of stay. No previous trials have been primarily directed at demonstrating that the use of drugs that prevent AF would shorten length of stay and reduce the costs of postoperative care.\n A randomized, double-blind, placebo-controlled trial of metoprolol was performed in patients immediately after nonemergent heart surgery. Metoprolol was given orally at a dose of 100 mg per day after the patient's arrival in the intensive care unit until hospital discharge or 14 days, whichever was sooner. This dose was increased to 150 mg per day after the enrollment of 411 patients. The primary outcome measure of the study was hospital length of stay from admission to intensive care unit until hospital discharge. There were 1000 patients enrolled, evenly distributed to the metoprolol and placebo groups.\n There was a 20% reduction in the risk of AF developing with metoprolol, from 39% of patients to 31% of patients (P =.01). There was no effect of treatment on hospital length of stay, which was 152 +/- 61 hours for placebo and 155 +/- 90 hours for metoprolol (P = 0.79). The cost of postoperative care in the 2 treatment groups was similar.\n Prophylactic metoprolol reduces the risk of AF after heart surgery. It does not reduce hospital length of stay. Although it is cost effective for the reduction of AF, it did not reduce the overall cost of care.", "The aim of this study was to determine the safety and efficacy of prophylactic high-dose intravenous aprotinin in reducing intraoperative blood loss in the neurosurgical population.\n A randomized, double-blind, placebo-controlled trial was conducted in parallel groups in two regional neurosurgical departments. One hundred patients with a preoperative diagnosis of intracranial meningioma or vestibular schwannoma subsequently confirmed on histological studies were included. All patients were older than 18 years of age, pregnancy had been excluded, there was no history of bleeding diathesis, no previous exposure to aprotinin, and no ingestion of antiplatelet or anticoagulant medications within the 2 weeks preceding surgery. Aprotinin was administered in doses of 30,000 kallikrein-inhibiting units (KIU)/kg body weight on induction of anesthesia and was continued as an infusion of 10,000 KIU/kg/hr until surgery was complete, or for a maximum of 8 hours. Intraoperative blood loss, blood transfusion, the Glasgow Outcome Scale score, and the Index of Independence were measured, and screening for deep vein thrombosis and the Mini-Mental State Examination were performed.\n Intraoperative blood loss was reduced from 1014 ml (geometric mean) to 508 ml (p = 0.028). Although this study was not designed to evaluate the need for blood transfusion, 37 U of blood was used in 11 patients in the aprotinin group and 58 U in 13 patients in the placebo group (not significant). There were no significant differences in postoperative thrombotic risk or other outcome measures between treatment groups. Aprotinin therefore can be safely used to reduce intraoperative blood loss in patients who are not receiving anticoagulation therapy.", "Atrial fibrillation (AF) is a common problem after CABG. Prevention with prophylactic drug therapy has had limited success, therefore alternative approaches are required. This study investigated the role of biatrial pacing compared with no pacing on AF incidence after isolated first-time CABG.\n During surgery, temporary pacing leads were placed in the lateral wall of the right atrium and at the roof of the left atrium in Bachmann's bundle to allow bipolar pacing and sensing at each site. After surgery, all patients were connected to an external pacemaker (Chorum ELA) that also acted as a Holter monitor. Patients were consecutively randomized to either 4 days of biatrial pacing at a base rate of 80 bpm or to no pacing (control group, base rate 30 bpm). End points included an episode of AF lasting >1 hour on pacemaker Holter, clinically detected AF, intensive care unit (ICU) and hospital stay, and postoperative complications. One hundred thirty patients were randomized. Biatrial pacing significantly reduced both monitored (13.8% versus 38.5%, P:=0.001) and clinical (10.8% versus 33.8%, P:=0.002) episodes of AF. Median ICU (19 versus 24 hours, P:=NS) and mean hospital stay (7.7+/-6.9 versus 9.7+/-10, P:=NS) did not significantly change. The number of postoperative complications was lower in the biatrial group (13 versus 35, P:=0. 001).\n Biatrial pacing after CABG significantly decreases the incidence of AF. This is associated with reduced postoperative complications and a trend toward reduced ICU and hospital stay.", "The authors determined whether the preoperative placement of a pulmonary artery catheter (PAC) with optimization of hemodynamics results in outcome improvement after elective vascular surgery.\n The PAC commonly is used not only in patients who are critically ill, but also perioperatively in major elective surgery. Few prospective studies exist documenting its usefulness.\n One hundred four consecutive patients were randomized to have a PAC placed the morning of operation (group I) or to have a PAC placed only if clinically indicated (group II). Group I patients were resuscitated to preestablished endpoints before surgery and kept at these points both intraoperatively and postoperatively. Group II patients received standard care.\n There was one death in each group. An intraoperative or postoperative complication developed in 13 patients in group I versus 7 patients in group II (p = not significant). Group I patients received more fluid than did group II patients (5137 +/- 315 mL vs. 3789 +/- 306 mL; p < 0.003). There was no significant difference in either overall or surgical intensive care unit length of stay. Only one patient in group II required a postoperative PAC.\n Routine PAC use in elective vascular surgery increases the volume of fluid given to patients without demonstrable improvement in morbidity or mortality.", "To study the efficacy of aprotinin in reducing whole blood loss after cardiac surgery with extracorporeal circulation.\n Two groups of patients undergoing cardiac surgery with extracorporeal circulation were studied. Group I (n = 51) received 2 x 10(6) KIU (kallikrein inhibiting units) of aprotinin upon anesthetic induction, a similar dose in the extracorporeal circulation priming pump, and a maintenance dose of 500,000 KIU/h until removal from the operating theater. Group II (n = 51) was the control group. Patients that had previously undergone surgery with extracorporeal circulation were excluded, as were those being treated with anti-coagulants or anti-aggregants. Data recorded were blood volume, transfusions needed in the first 24 h, and blood derivatives used throughout the hospital stay. Postoperative kidney function was also determined. The occurrence of acute myocardial infarction in patients undergoing myocardial revascularization was also noted.\n Group I required a mean of 2.40 U of concentrated red blood per patient during the first postoperative day, as opposed to a mean of 4.3 U in group II (p < 0.001). Blood loss through drains was also less in group I than in group II (431.82 vs 895.29 ml; p < 0.001). Total blood needed during the hospital stay was 3.50 units per patient in group I vs 5.40 U in group II (p < 0.001). Urea and creatinine were similar in the two groups before and after surgery (p = NS), and there were no significant differences in the number of cases of acute myocardial infarction in the two groups (3 in group I and 2 in group II).\n Administration of high doses of aprotinin is an effective technique for reducing the need for whole blood in patients requiring extracorporeal circulation during surgery. The technique does not compromise kidney function or increase the risk of perioperative acute myocardial infarction.", "The balance between the benefits and the risks of pulmonary-artery catheters (PACs) has not been established.\n We evaluated the relationship of benefits and risks of PACs in 1000 patients with established acute lung injury in a randomized trial comparing hemodynamic management guided by a PAC with hemodynamic management guided by a central venous catheter (CVC) using an explicit management protocol. Mortality during the first 60 days before discharge home was the primary outcome.\n The groups had similar baseline characteristics. The rates of death during the first 60 days before discharge home were similar in the PAC and CVC groups (27.4 percent and 26.3 percent, respectively; P=0.69; absolute difference, 1.1 percent; 95 percent confidence interval, -4.4 to 6.6 percent), as were the mean (+/-SE) numbers of both ventilator-free days (13.2+/-0.5 and 13.5+/-0.5; P=0.58) and days not spent in the intensive care unit (12.0+/-0.4 and 12.5+/-0.5; P=0.40) to day 28. PAC-guided therapy did not improve these measures for patients in shock at the time of enrollment. There were no significant differences between groups in lung or kidney function, rates of hypotension, ventilator settings, or use of dialysis or vasopressors. Approximately 90 percent of protocol instructions were followed in both groups, with a 1 percent rate of crossover from CVC- to PAC-guided therapy. Fluid balance was similar in the two groups, as was the proportion of instructions given for fluid and diuretics. Dobutamine use was uncommon. The PAC group had approximately twice as many catheter-related complications (predominantly arrhythmias).\n PAC-guided therapy did not improve survival or organ function but was associated with more complications than CVC-guided therapy. These results, when considered with those of previous studies, suggest that the PAC should not be routinely used for the management of acute lung injury. (ClinicalTrials.gov number, NCT00281268.).\n Copyright 2006 Massachusetts Medical Society.", "Peptic ulcer bleeding is a common and potentially fatal condition. For patients with bleeding peptic ulcers that display major endoscopic stigmata of recent hemorrhage, a combination of endoscopic and pharmacologic therapy is the current standard management.\n To show our experience with management of peptic ulcer bleeding.\n Patients who presented with gastrointestinal bleeding caused by peptic ulcer or recent history (< 24 h before presentation) of hematemesis and/or melena admitted to our hospital emergency departments, and patients whose ulcer hemorrhage started after hospitalization for an unrelated medical or surgical condition.\n Patients with actively bleeding ulcers and those with nonbleeding visible vessel or adherent clot were treated with epinephrine injection and/or endoscopic hemoclips, and randomized to receive intravenous pantoprasole according to the continuous regimen (dose of 5 x 40 mg in continuous infusion of 8 mg/h for 72 h) or the standard regimen (40 mg bolus of PPI twice daily for 3 days). After the infusion, all patients were given 40 mg PPI twice daily orally. The primary end point was the in-hospital rebleeding rate, as discovered by the repeated endoscopy.\n Bleeding recurred in 5 of 34 patients (14.7%) receiving the intensive regimen, and in 8 of 35 (22.8%) patients receiving the standard regimen. Hemoglobin (g/l) rate in standard regimen group was 93.5 +/- 23.8, and in intensive regimen group 106.6 +/- 22.4 (P = 0.042). Mean units of blood transfused for all patients in group were 71.8 +/- 45.8 in the intensive and 45.3 +/- 50.2 in the standard regimen group (P = 0.0257). The duration of hospital stay was 6.4 +/- 2.8 in standard group and 5.8 +/- 2.8 in the intensive group (P = 0.40).\n In patients with bleeding peptic ulcers with successful endoscopic hemostasis the standard PPI regimen had advantage on transfusion requirements, but no advantage with respect to in-hospital rates of rebleeding rates, need for surgery, length of hospital stay, or death, which corresponds with recent studies.", "The purpose of the study was to determine whether an education initiative aimed at improving central venous catheter insertion and care could decrease the rate of primary bloodstream infections.\n Pre- and postintervention observational study.\n Eighteen-bed surgical/burn/trauma intensive care unit (ICU) in an urban teaching hospital.\n A total of 4,283 patients were admitted to the ICU between January 1, 1998, and December 31, 2000.\n A program primarily directed toward registered nurses was developed by a multidisciplinary task force to highlight correct practice for central venous catheter insertion and maintenance. The program consisted of a 10-page self-study module on risk factors and practice modifications involved in catheter-related infections as well as a verbal in-service at staff meetings. Each participant was required to take a pretest before taking the study module and an identical test after its completion. Fact sheets and posters reinforcing the information in the study module were also posted throughout the ICU.\n Seventy-four primary bloodstream infections occurred in 6874 catheter days (10.8 per 1000 catheter days) in the 18 months before the intervention. After the implementation of the education module, the number of primary bloodstream infections fell to 26 in 7044 catheter days (3.7 per 1000 catheter days), a decrease of 66% (p < .0001). The estimated cost savings secondary to the decreased infection rate for the 18 months after the intervention was between $185,000 and $2.808 million.\n A focused intervention primarily directed at the ICU nursing staff can lead to a dramatic decrease in the incidence of primary bloodstream infections. Educational programs may lead to a substantial decrease in cost, morbidity, and mortality attributable to central venous catheterization." ]	It remains uncertain whether increasing blood flow using fluids, with or without inotropes or vasoactive drugs, reduces mortality in adults undergoing surgery. The primary analysis in this review (mortality at longest follow-up) showed no difference between the intervention and control, but this result was sensitive to the method of analysis, the withdrawal of studies with methodological limitations, and is dominated by a single large RCT. Overall, for every 100 patients in whom blood flow is increased perioperatively to defined goals, one can expect 13 in 100 patients (from 40/100 to 27/100) to avoid a complication, 2/100 to avoid renal impairment (from 8/100 to 6/100), 5/100 to avoid respiratory failure (from 10/100 to 5/100), and 4/100 to avoid postoperative wound infection (from 10/100 to 6/100). On average, patients receiving the intervention stay in hospital one day less. It is unlikely that the intervention causes harm. The balance of current evidence does not support widespread implementation of this approach to reduce mortality but does suggest that complications and duration of hospital stay are reduced.
CD004581	[ "12790861", "15644657", "2245613", "15350708", "10990101", "11398690", "16511633", "1524162", "18829800", "8143475", "15333426", "16394688" ]	[ "A prospective, randomized study of ventilator-associated pneumonia in patients using a closed vs. open suction system.", "Ventilator-associated pneumonia using a closed versus an open tracheal suction system.", "Incidence of colonization, nosocomial pneumonia, and mortality in critically ill patients using a Trach Care closed-suction system versus an open-suction system: prospective, randomized study.", "Comparison of the effect of closed versus open endotracheal suction systems on the development of ventilator-associated pneumonia.", "Nosocomial pneumonia in mechanically ventilated patients, a prospective randomised evaluation of the Stericath closed suctioning system.", "Closed system endotracheal suctioning maintains lung volume during volume-controlled mechanical ventilation.", "Tracheal suction by closed system without daily change versus open system.", "[Endotracheal suctioning using a 24-hour continuous system. Can costs and waste products be reduced?].", "Randomized, controlled trial on tracheal colonization of ventilated infants: can gravity prevent ventilator-associated pneumonia?", "Closed versus open endotracheal suctioning: costs and physiologic consequences.", "Closed suctioning system reduces cross-contamination between bronchial system and gastric juices.", "Open and closed-circuit endotracheal suctioning in acute lung injury: efficiency and effects on gas exchange." ]	[ "The objective of this study was to verify the incidence of nosocomial pneumonia in intubated and extended mechanically ventilated patients having endotracheal suctioning by an open vs. closed suction method aiming to decrease nosocomial pneumonia. Twenty-four (51.1%) patients received open-tracheal suction and 23 (48.9%) received closed-tracheal suction. The inclusion criteria were: surgical and medical patients older than 13 years, undergoing mechanical ventilation for more than 48 hours. Additional data were gathered using the Acute Physiology and Chronic Health Evaluation II, and details on smoking, alcoholism, diabetes mellitus, renal failure, previous lung disease, and previous use of antibiotics, steroids, H2 antagonists and antacids. Among the 24 patients having open-tracheal suction, 11 developed nosocomial pneumonia while of the 23 patients undergoing closed-tracheal suction, seven developed infection (P = 0.278). Risk factors for nosocomial pneumonia were not significantly different between the two groups. In the final logistical regression model the following variables remained: groups (open and closed) [odds ratio (OR) = 0.014; confidence interval (CI) = 0.001-0.416; P = 0.014] and use of prior antibiotics (OR = 2.297; CI = 1.244-4.242; P = 0.008). Use of a closed suction system did not decrease the incidence of nosocomial pneumonia when compared with the open system. The exogenous risk factors were the most important for acquiring this infection.", "The aim of this study was to analyze the prevalence of ventilator-associated pneumonia (VAP) using a closed-tracheal suction system vs. an open system.\n Prospective and randomized study, from October 1, 2002, to December 31, 2003.\n A 24-bed medical-surgical intensive care unit in a 650-bed tertiary hospital.\n Patients requiring mechanical ventilation for >24 hrs.\n Patients were randomized into two groups; one group was suctioned with the closed-tracheal suctioning system and another group with the open system.\n Throat swabs were taken at admission and twice a week until discharge to classify pneumonia in endogenous and exogenous.\n A total of 443 patients (210 with closed-tracheal suction system and 233 with the open system) were included. There were no significant differences between groups of patients in age, sex, diagnosis groups, mortality, number of aspirations per day, and Acute Physiology and Chronic Health Evaluation II score. No significant differences were found in either the percentage of patients who developed VAP (20.47% vs. 18.02%) or in the number of VAP cases per 1000 mechanical ventilation-days (17.59 vs. 15.84). There were also no differences in the VAP incidence by mechanical ventilation duration. At the same time, we did not find any differences in the incidence of exogenous VAP. Likewise, there were also no differences in the microorganisms responsible for pneumonia. Patient cost per day for the closed suction was more expensive than the open suction system (11.11 US dollars +/- 2.25 US dollars vs. 2.50 US dollars +/- 1.12 US dollars, p < .001).\n We conclude that in our study, the closed-tracheal suction system did not reduce VAP incidence, even for exogenous pneumonia.", "Eighty-four intubated, mechanically ventilated patients were prospectively evaluated for incidences of colonization and nosocomial pneumonias dependent on whether they received endotracheal suctioning by an \"open\" suction method vs. \"closed\" suction (Trach Care Closed Suction System) method. Results show that closed suctioning is associated with a significant (67% vs. 39% p less than .02) increase in colonization compared with open suctioning. However, difference in the incidence of nosocomial pneumonia was not significantly (26% vs. 29%) different between closed and open suctioning. Differences in severity of illness (Acute Physiology and Chronic Health Evaluation II and Therapeutic Intervention Scoring System), age, sex, presence of NG tubes, use of H2 antagonists or antacids, use of antibiotics, and history of smoking were all nonsignificant. Survival analysis demonstrated that the probability of survival without developing nosocomial pneumonia was greater among closed-suctioning patients vs. open-suctioned patients (p less than .03). This study shows that suctioning performed via the Trach Care closed-suction system increases the incidence of colonization but not the incidence of nosocomial pneumonia, and may actually decrease mortality when compared with open-suction systems.", "The aim of this study was to compare the effect of closed versus open endotracheal suction systems on the development of ventilator-associated pneumonia (VAP). A prospective, randomized, controlled trial was performed in a medical intensive care unit (MICU) of a university hospital in patients who received mechanical ventilation for more than 48 h. Patients were randomized to receive endotracheal suction with either closed catheters (closed suction group; N-41) or single-use catheters (open suction group; N=37). Cultures were taken from the ventilator tubing of 42 patients to determine the rate of colonization. There was no difference between the groups in terms of the frequency of development of VAP, mortality in the MICU, length of MICU stay and duration of mechanical ventilation. Thirteen patients in the open suction group and 16 patients in the closed suction group became colonized (P=0.14). The colonization rates by Acinetobacter spp. and Pseudomonas aeruginosa were more frequent in the closed suction group than in the open suction group (P<0.01 and P=0.04, respectively). In conclusion, closed endotracheal suction resulted in increased colonization rates of ventilator tubing with multi drug-resistant micro-organisms but did not increase the development of VAP and MICU outcome compared with open endotracheal suction.", "To compare the ventilator-associated pneumonia (VAP) incidence rates in mechanically ventilated patients according to the type of endotracheal suctioning (closed versus open).\n The Neurosurgery Intensive Care Unit of the Grenoble University Hospital, France.\n A prospective randomised study performed after a 6-month period of nursing personnel training.\n One hundred four consecutive patients needing mechanical ventilation for more than 48 h were randomised into two groups. To be eligible, patients had to have no active infection or respiratory affection in their passes. In the Stericath group (S+, n = 54), patients were not disconnected from the ventilator during suctioning. The others were routinely managed (S-, n = 50). In both groups patterns of frequency and duration of suctioning were performed according to a standardised protocol.\n The non-adjusted incidence rate of VAP was lower for S+ than for S- (7.32 versus 15.89 per 1000 patient-days, p = 0.07). Multivariate analysis performed using the Cox model showed an adjusted risk of VAP 3.5 times higher in S- (95% CI: 11.00-12.33). The risk being 4.3 higher in patients receiving gastric acid secretion inhibitors (1.08-16.82). In non-censored cases (n = 76) length of ICU stay increased by an average of 16.8 days when VAP was present (p = 0.0008). No adverse effect due to Stericath use was noted and volume of tracheal aspirate was similar between groups (p = 0.178).\n The use of Stericath reduced the incidence rate of VAP without demonstrating any adverse effect.", "A closed suction system (CS) maintains connection with the mechanical ventilator during tracheal suctioning and is claimed to limit loss in lung volume and oxygenation. We compared changes in lung volume, oxygenation, airway pressure and hemodynamics during endotracheal suctioning performed with CS and with an open suction system (OS).\n Prospective, randomized study.\n Intensive care unit in a university hospital.\n We enrolled ten patients, volume-controlled (VC) ventilated with a Siemens Servo 900 ventilator (PaO2/FIO2 192 +/- 70, PEEP 10.7 +/- 3.9 cmH2O).\n We performed four consecutive tracheal suction maneuvers, two with CS and two with OS, at 20-min intervals. During the suction maneuvers continuous suction was applied for 20 s.\n We measured end-expiratory lung volume changes (delta VL), tidal volume (VTrt), respiratory rate (RR) and minute volume (VErt) by respiratory inductive plethysmography; arterial oxygen saturation (SpO2), airway pressure and arterial pressure (PA). Loss in lung volume during OS (delta VL 1.2 +/- 0.7 l) was significantly higher than during CS (delta VL 0.14 +/- 0.1 l). During OS we observed a marked drop in SpO2, while during CS the change was only minor. During CS ventilation was not interrupted and we observed an immediate increase in RR (due to the activation of the ventilator's trigger), while VTrt decreased, VErt was maintained.\n Avoiding suction-related lung volume loss can be helpful in patients with an increased tendency to alveolar collapse; CS allows suctioning while avoiding dramatic drops in lung volumes and seems to be safe during the VC ventilation setting that we used.", "Tracheal suctioning costs are higher with a closed tracheal suction system (CTSS) than with an open system (OTSS), due to the need for complete daily change as recommended by the manufacturer. However, is it necessary to change the closed system daily?\n To evaluate the tracheal suctioning costs and incidence of ventilator-associated pneumonia (VAP) using closed system without daily change vs OTSS.\n Prospective and randomised study.\n An Intensive Care Unit in a university hospital.\n Patients requiring mechanical ventilation.\n Patients were randomly assigned to CTSS without daily change or OTSS. We used a CTSS that allowed partial or complete change.\n There were no significant differences between both groups of patients (236 with CTSS and 221 with OTSS) in gender, age, diagnosis, APACHE-II score, mortality, number of aspirations per day, percentage of patients who developed VAP (13.9 vs 14.1%) or the number of ventilator-associated pneumonia per 1000 days of mechanical ventilation (14.1 vs 14.6). There were not significant differences in tracheal suctioning costs per patient/day between CTSS vs OTSS (2.3+/-3.7 vs 2.4+/-0.5 Euros; p=0.96); however, when length of mechanical ventilation was lower than 4 days, the cost was higher with CTSS than with OTSS (7.2+/-4.7 vs 1.9+/-0.6 Euros; p<0.001); and when length of mechanical ventilation was higher than 4days, the cost was lower with CTSS than with OTSS (1.6+/-2.8 vs 2.5+/-0.5 Euros; p<0.001).\n CTSS without daily change is the optimal option for patients needing tracheal suction longer than 4 days.", "Suctioning of the airways is often required in critically ill, intubated, or tracheotomised patients. In addition to the primary cost of these disposable materials, expenditures for waste disposal and environmental problems due to plastics should also be considered. In this study, the primary costs and amount of waste products of the closed suction system \"Trach Care\" were compared with a conventional disposable system. Other advantages and disadvantages of a closed suction system are discussed. METHODS. In this prospective, randomised investigation, both the open disposable suction system and the closed Trach Care system were used, in 60 patients (30 in each group) who were intubated for 1 week or more. During the first 7 days, we counted the number of times endotracheal suctioning was performed and measured the time it took. The costs of purchasing the systems, amounts of waste products, and costs of disposal were compared. RESULTS. The frequency of endotracheal suctioning was quite different from patient to patient and varied from 6 to 41 times per day. On average it was necessary 15 times per day per patient in both groups. Using the disposable system, a mean time of 3.5 min was measured in contrast to 2.5 min with the closed system. The costs of purchase were much lower with the disposable system taking into account all materials needed (17.36 DM vs 53.36 DM per day), whereas the weight of litter produced by the closed system was lower (429 g vs 745 g per day), the costs of disposal being accordingly different. During endotracheal suctioning O2 desaturation was not observed with the closed system, whereas in patients with acute respiratory failure O2 saturation fell rapidly from 90% to as far as 70% when a disposable system was used. CONCLUSION. The closed Trach Care suction system is more expensive to acquire, but may reduce the risk of exogenous nosocomial pneumonias as disconnections from the ventilator are minimised. The workload, weight of waste products, and costs of disposal are lower using the Trach Care system. From the physician's viewpoint, the main advantage of the Trach Care system becomes evident in patients with acute respiratory failure and patients with elevated intracranial pressure. In these cases, we now favor the Trach Care system as a matter of principle.", "The goal was to test the hypothesis that intubated infants positioned on their sides would be less likely to contract bacterial colonization in their tracheae, compared with those positioned supine.\n We conducted a prospective, randomized, controlled trial with 60 intubated infants; 30 infants were positioned supine (supine group), and 30 infants were maintained in the lateral position (lateral group). Tracheal aspirates were cultured and bacterial colony counts were recorded after 48 hours and after 5 days of mechanical ventilation.\n After 2 days, the numbers of positive tracheal cultures in the supine group (67%) and in the lateral group (47%) showed no statistical difference. After 5 days of mechanical ventilation, tracheal cultures differed significantly between groups. Cultures were positive for 26 infants (87%) in the supine group and 9 infants (30%) in the lateral group. Compared with the lateral group, more infants in the supine group experienced increased colony counts or had new organisms in their tracheal aspirates over time (21 vs 8 infants). The most common organisms isolated from tracheal aspirates in both groups were Gram-negative rods.\n Respiratory contamination is very common among ventilated infants. Therefore, judicious use of mechanical ventilation cannot be overemphasized. Gravitational force can ameliorate the onset of respiratory colonization. The mechanism and clinical applicability of such observations need to be explored further.", "To examine the physiologic consequences and costs associated with two methods of endotracheal suctioning: closed vs. open.\n A prospective, randomized, controlled study.\n An eight-bed trauma intensive care unit (ICU) in a 460-bed level I trauma center.\n The study included 35 trauma/general surgery patients (16 in the open suction group, 19 in the closed suction group) who were treated with a total of 276 suctioning procedures (127 open, 149 closed).\n Physiologic data collected after hyperoxygenation, immediately after suctioning, and 30 secs after suctioning, were compared with baseline values. Open endotracheal suctioning resulted in significant increases in mean arterial pressure throughout the suctioning procedure. Both methods resulted in increased mean heart rates. However, 30 secs after the procedure, the open-suction method was associated with a significantly higher mean heart rate than was the closed method. Closed suctioning was associated with significantly fewer dysrhythmias. Arterial oxygen saturation and systemic venous oxygen saturation decreased with open suctioning. In contrast, arterial oxygen saturation and systemic venous oxygen saturation increased with the closed suction method. There was no difference between the two methods in the occurrence of nosocomial pneumonia. Open endotracheal suctioning cost $1.88 more per patient per day and required more nursing time.\n The closed suction method resulted in significantly fewer physiologic disturbances. Closed suctioning appears to be an effective and cost-efficient method of endotracheal suctioning that is associated with fewer suction-induced complications.", "In this prospective, randomized study, we evaluated whether a closed suctioning (CS) system (TrachCare) influences crossover contamination between bronchial system and gastric juices when compared with an open suctioning system (OS). The secondary aims were an analysis of the frequency of ventilator-associated pneumonia (VAP) and an analysis of alteration in gas exchange. Antibiograms were performed from tracheal secretions and gastric juice aspirates on Days 1 and 3 of intubation in 24 patients in a medical intensive care unit. Five cross-contaminations were observed in the OS group on Day 3 versus Day 1; the 5 strains shared common genotypes as determined by random amplification of polymorphic DNA. No cross-contaminations were seen in the CS group (P = 0.037). VAP occurred in 5 patients of the OS group but in none of the CS group patients (P = 0.037). Spao(2) decreased significantly in the OS group compared with presuctioning values--the opposite of the CS group. Whereas presuctioning values were comparable between groups, postsuctioning Spao(2) was significantly higher in the CS group. CS significantly reduced cross-contamination between bronchial system and gastric juices and reduced the incidence of VAP when compared with OS. Hypoxic phases can be reduced by the help of CS.", "Closed-circuit endotracheal suctioning (CES) is advocated for preventing hypoxemia caused by the loss of lung volume resulting from open endotracheal suctioning (OES). However, the efficiency of CES and OES on tracheal secretion removal has never been compared in patients with acute lung injury. The authors designed a two-part study aimed at comparing gas exchange and efficiency between OES and CES performed at two levels of negative pressure.\n Among 18 patients with acute lung injury, 9 underwent CES and OES at 3-h intervals in a random order using a negative pressure of -200 mmHg. Nine other patients underwent CES twice using two levels of negative pressure (-200 and -400 mmHg) applied in a random order. After each CES, a recruitment maneuver was performed using 20 consecutive hyperinflations. Tracheal aspirates were weighed after each suctioning procedure. Arterial blood gases were continuously recorded using an intravascular sensor.\n Open endotracheal suctioning induced a significant 18% decrease in arterial oxygen tension (Pa(O2)) (range, +13 to -71%) and an 8% increase in arterial carbon dioxide tension (Pa(CO2)) (range, -2 to +16%) that persisted 15 min after the end of the procedure. CES using -200 cm H2O did not change Pa(O2), but tracheal aspirate mass was lower compared with OES (0.6 +/- 1.0 vs. 3.2 +/- 5.1 g; P = 0.03). Increasing negative pressure to -400 cm H2O during CES did not change Pa(O2) but increased the tracheal aspirate mass (1.7 +/- 1.6 vs. 1.0 +/- 1.3 g; P = 0.02).\n Closed-circuit endotracheal suctioning followed by a recruitment maneuver prevents hypoxemia resulting from OES but decreases secretion removal. Increasing suctioning pressure enhances suctioning efficiency without impairing gas exchange." ]	Results from 16 trials showed that suctioning with either closed or open tracheal suction systems did not have an effect on the risk of ventilator-associated pneumonia or mortality. More studies of high methodological quality are required, particularly to clarify the benefits and hazards of the closed tracheal suction system for different modes of ventilation and in different types of patients.
CD000563	[ "16801628", "9469327", "21145284", "16226397" ]	[ "Breast-conserving treatment with or without radiotherapy in ductal carcinoma-in-situ: ten-year results of European Organisation for Research and Treatment of Cancer randomized phase III trial 10853--a study by the EORTC Breast Cancer Cooperative Group and EORTC Radiotherapy Group.", "Lumpectomy and radiation therapy for the treatment of intraductal breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-17.", "Effect of tamoxifen and radiotherapy in women with locally excised ductal carcinoma in situ: long-term results from the UK/ANZ DCIS trial.", "A phase III randomized study on the sequencing of radiotherapy and chemotherapy in the conservative management of early-stage breast cancer." ]	[ "The European Organisation for Research and Treatment of Cancer conducted a randomized trial investigating the role of radiotherapy (RT) after local excision (LE) of ductal carcinoma-in-situ (DCIS) of the breast. We analyzed the efficacy of RT with 10 years follow-up on both the overall risk of local recurrence (LR) and related to clinical, histologic, and treatment factors.\n After complete LE, women with DCIS were randomly assigned to no further treatment or RT (50 Gy). One thousand ten women with mostly (71%) mammographically detected DCIS were included. The median follow-up was 10.5 years.\n The 10-year LR-free rate was 74% in the group treated with LE alone compared with 85% in the women treated by LE plus RT (log-rank P < .0001; hazard ratio [HR] = 0.53). The risk of DCIS and invasive LR was reduced by 48% (P = .0011) and 42% (P = .0065) respectively. Both groups had similar low risks of metastases and death. At multivariate analysis, factors significantly associated with an increased LR risk were young age (< or = 40 years; HR = 1.89), symptomatic detection (HR = 1.55), intermediately or poorly differentiated DCIS (as opposed to well-differentiated DCIS; HR = 1.85 and HR = 1.61 respectively), cribriform or solid growth pattern (as opposed to clinging/micropapillary subtypes; HR = 2.39 and HR = 2.25 respectively), doubtful margins (HR = 1.84), and treatment by LE alone (HR = 1.82). The effect of RT was homogeneous across all assessed risk factors.\n With long-term follow-up, RT after LE for DCIS continued to reduce the risk of LR, with a 47% reduction at 10 years. All patient subgroups benefited from RT.", "In 1993, findings from a National Surgical Adjuvant Breast and Bowel Project (NSABP) trial to evaluate the worth of radiation therapy after lumpectomy concluded that the combination was more beneficial than lumpectomy alone for localized intraductal carcinoma-in-situ (DCIS). This report extends those findings.\n Women (N = 818) with localized DCIS were randomly assigned to lumpectomy or lumpectomy plus radiation (50 Gy). Tissue was removed so that resected specimen margins were histologically tumor-free. Mean follow-up time was 90 months (range, 67 to 130). Size and method of tumor detection were determined by central clinical, mammographic, and pathologic assessment. Life-table estimates of event-free survival and survival, average annual rates of occurrence for specific events, relative risks for event-specific end points, and cumulative probability of specific events comprising event-free survival are presented.\n The benefit of lumpectomy plus radiation was virtually unchanged between 5 and 8 years of follow-up and was due to a reduction in invasive and noninvasive ipsilateral breast tumors (IBTs). Incidence of locoregional and distant events remained similar in both treatment groups; deaths were only infrequently related to breast cancer. Incidence of noninvasive IBT was reduced from 13.4% to 8.2% (P = .007), and of invasive IBT, from 13.4% to 3.9% (P < .0001). All cohorts benefited from radiation regardless of clinical or mammographic tumor characteristics.\n Through 8 years of follow-up, our findings continue to indicate that lumpectomy plus radiation is more beneficial than lumpectomy alone for women with localized, mammographically detected DCIS. When evaluated according to the mammographic characteristics of their DCIS, all groups benefited from radiation.", "Initial results of the UK/ANZ DCIS (UK, Australia, and New Zealand ductal carcinoma in situ) trial suggested that radiotherapy reduced new breast events of ipsilateral invasive and ductal carcinoma in situ (DCIS) compared with no radiotherapy, but no significant effects were noted with tamoxifen. Here, we report long-term results of this trial.\n Women with completely locally excised DCIS were recruited into a randomised 2×2 factorial trial of radiotherapy, tamoxifen, or both. Randomisation was independently done for each of the two treatments (radiotherapy and tamoxifen), stratified by screening assessment centre, and blocked in groups of four. The recommended dose for radiation was 50 Gy in 25 fractions over 5 weeks (2 Gy per day on weekdays), and tamoxifen was prescribed at a dose of 20 mg daily for 5 years. Elective decision to withhold or provide one of the treatments was permitted. The endpoints of primary interest were invasive ipsilateral new breast events for the radiotherapy comparison and any new breast event, including contralateral disease and DCIS, for tamoxifen. Analysis of each of the two treatment comparisons was restricted to patients who were randomly assigned to that treatment. Analyses were by intention to treat. All trial drugs have been completed and this study is in long-term follow-up. This study is registered, number ISRCTN99513870.\n Between May, 1990, and August, 1998, 1701 women were randomly assigned to radiotherapy and tamoxifen, radiotherapy alone, tamoxifen alone, or to no adjuvant treatment. Seven patients had protocol violations and thus 1694 patients were available for analysis. After a median follow-up of 12·7 years (IQR 10·9-14·7), 376 (163 invasive [122 ipsilateral vs 39 contralateral], 197 DCIS [174 ipsilateral vs 17 contralateral], and 16 of unknown invasiveness or laterality) breast cancers were diagnosed. Radiotherapy reduced the incidence of all new breast events (hazard ratio [HR] 0·41, 95% CI 0·30-0·56; p<0·0001), reducing the incidence of ipsilateral invasive disease (0·32, 0·19-0·56; p<0·0001) as well as ipsilateral DCIS (0·38, 0·22-0·63; p<0·0001), but having no effect on contralateral breast cancer (0·84, 0·45-1·58; p=0·6). Tamoxifen reduced the incidence of all new breast events (HR 0·71, 95% CI 0·58-0·88; p=0·002), reducing recurrent ipsilateral DCIS (0·70, 0·51-0·86; p=0·03) and contralateral tumours (0·44, 0·25-0·77; p=0·005), but having no effect on ipsilateral invasive disease (0·95, 0·66-1·38; p=0·8). No data on adverse events except cause of death were collected for this trial.\n This updated analysis confirms the long-term beneficial effect of radiotherapy and reports a benefit for tamoxifen in reducing local and contralateral new breast events for women with DCIS treated by complete local excision.\n Cancer Research UK and the Australian National Health and Medical Research Council.\n Copyright Â© 2011 Elsevier Ltd. All rights reserved.", "To compare two different timings of radiation treatment in patients with breast cancer who underwent conservative surgery and were candidates to receive adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy.\n A total of 206 patients who had quadrantectomy and axillary dissection for breast cancer and were planned to receive adjuvant CMF chemotherapy were randomized to concurrent or sequential radiotherapy. Radiotherapy was delivered only to the whole breast through tangential fields to a dose of 50 Gy in 20 fractions over 4 weeks, followed by an electron boost of 10-15 Gy in 4-6 fractions to the tumor bed.\n No differences in 5-year breast recurrence-free, metastasis-free, disease-free, and overall survival were observed in the two treatment groups. All patients completed the planned radiotherapy. No evidence of an increased risk of toxicity was observed between the two arms. No difference in radiotherapy and in the chemotherapy dose intensity was observed in the two groups.\n In patients with negative surgical margins receiving adjuvant chemotherapy, radiotherapy can be delayed to up to 7 months. Concurrent administration of CMF chemotherapy and radiotherapy is safe and might be reserved for patients at high risk of local recurrence, such as those with positive surgical margins or larger tumor diameters." ]	This review confirms the benefit of adding radiotherapy to breast conserving surgery for the treatment of all women diagnosed with DCIS. No long-term toxicity from use of radiotherapy was identified.
CD004975	[ "9109139", "14506028", "15361722", "10768519", "9181384" ]	[ "Continuous twice daily or once daily amoxicillin prophylaxis compared with placebo for children with recurrent acute otitis media.", "High-dose azithromycin versus high-dose amoxicillin-clavulanate for treatment of children with recurrent or persistent acute otitis media.", "Comparison of five-day cefdinir treatment with ten-day low dose amoxicillin/clavulanate treatment for acute otitis media.", "Efficacy and safety of amoxycillin/clavulanate (Augmentin) twice daily versus three times daily in the treatment of acute otitis media in children. The Augmentin 454 Study Group.", "Efficacy of twice-daily dosing of amoxycillin/clavulanate in acute otitis media in children." ]	[ "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.", "Infants and young children, especially those in day care, are at risk for recurrent or persistent acute otitis media (AOM). There are no data on oral alternatives to high-dose amoxicillin-clavulanate for treating AOM in these high-risk patients. In this double-blind, double-dummy multicenter clinical trial, we compared a novel, high-dose azithromycin regimen with high-dose amoxicillin-clavulanate for treatment of children with recurrent or persistent AOM. Three hundred four children were randomized; 300 received either high-dose azithromycin (20 mg/kg of body weight once a day for 3 days) or high-dose amoxicillin-clavulanate (90 mg/kg divided twice a day for 10 days). Tympanocentesis was performed at baseline; clinical response was assessed at day 12 to 16 and day 28 to 32. Two-thirds of patients were aged < or =2 years. A history of recurrent, persistent, or recurrent plus persistent AOM was noted in 67, 18, and 14% of patients, respectively. Pathogens were isolated from 163 of 296 intent-to-treat patients (55%). At day 12 to 16, clinical success rates for azithromycin and amoxicillin-clavulanate were comparable for all patients (86 versus 84%, respectively) and for children aged < or =2 years (85 versus 79%, respectively). At day 28 to 32, clinical success rates for azithromycin were superior to those for amoxicillin-clavulanate for all patients (72 versus 61%, respectively; P = 0.047) and for those aged < or =2 years (68 versus 51%, respectively; P = 0.017). Per-pathogen clinical efficacy against Streptococcus pneumoniae and Haemophilus influenzae was comparable between the two regimens. The rates of treatment-related adverse events for azithromycin and amoxicillin-clavulanate were 32 and 42%, respectively (P = 0.095). Corresponding compliance rates were 99 and 93%, respectively (P = 0.018). These data demonstrate the efficacy and safety of high-dose azithromycin for treating recurrent or persistent AOM.", "Short course beta-lactam antibiotic therapy for acute otitis media (AOM) should improve patient adherence, but it has not been evaluated since the heptavalent pneumococcal conjugate vaccine became routinely used in the United States.\n In a prospective, investigator-blinded, multicenter study, 425 patients, age 6 months-6 years, with a clinical diagnosis of nonrefractory AOM were randomized to receive either 5 days of cefdinir therapy (14 mg/kg divided twice daily) or 10 days of amoxicillin/clavulanate therapy (45/6.4 mg/kg divided twice daily). Clinical response was assessed at end of therapy (2-4 days postantibiotic, respectively) and week 4 (study days 25-28).\n With no difference in demographics between treatment groups, overall the mean age (+/-SD) was 2.8 +/- 1.8 years, 65% had received conjugated pneumococcal vaccination and 48% had bilateral AOM. The satisfactory clinical response rate at end of therapy was comparable for cefdinir versus amoxicillin/clavulanate (88%, 170 of 194 versus 85%, 164 of 192; 95% CI -4.9, 9.3). Although this must be interpreted with caution, cefdinir showed an apparent trend for higher efficacy than amoxicillin/clavulanate (92%, 72 of 78 versus 77%, 55 of 71; P = 0.019) in a subsample of patients 6-24 months old who had received conjugated pneumococcal vaccination. The incidence of drug-related adverse events was less for cefdinir than for amoxicillin/clavulanate (24%, 50 of 211 versus 38%, 82 of 214; P = 0.0018)\n For children with nonrefractory AOM, based only on clinical endpoints, 5 days of therapy with cefdinir 14 mg/kg divided twice daily was comparable overall with 10 days of therapy with low dose amoxicillin/clavulanate 45/6.4 mg/kg divided twice daily.", "This multicenter, randomized, single-blind study compared the efficacy and safety of a new, twice-daily formulation of amoxycillin/clavulanate (Augmenting) with the standard three-times-daily formulation. Children with a clinical diagnosis of acute otitis media, aged between 2 months and 12 years, received either amoxycillin/clavulanate 45/6.4 mg/kg/day twice-daily (b.d.) (range 38.3/5.5-76.2/10.9 mg/kg/day) or amoxycillin/clavulanate 40/10 mg/kg/day three-times-daily (t.d.s.) (range 25/6.25-56/14 mg/kg/day) for 7 or 10 days. Patients were evaluated during therapy (Days 3-5), at the end of therapy (Days 7-12) and at follow-up (Days 38-42). At the end of therapy, for the intent-to-treat and per-protocol populations, respectively, clinical success (cure) was achieved by approximately 94% of patients in both treatment groups. A successful bacteriological response at the end of therapy (Visit 3) was documented in 7/9 patients (77.8%) in the twice-daily group and in 11/13 patients (84.6%) in the three-times-daily group. At follow-up (Visit 4), 93.3% of patients in the twice-daily group and 87.9% in the three-times-daily group continued to have a clinically successful response. Both treatment regimens were well tolerated, with most adverse events being of a mild-moderate and transient nature. The most common treatment-related adverse event was diarrhea, occurring in 7.2% of patients in the twice-daily group and in 10.7% of the three-times-daily group. In total, 173 patients (82.8%) in the twice-daily group and 151 patients (73.3%) in the three-times-daily group were compliant with medication. In conclusion, this study confirms that b.d. amoxycillin/clavulanate is an effective treatment for pediatric acute otitis media and demonstrates that the b.d. and t.d.s. formulations of amoxycillin/clavulanate produce equivalent efficacy. Furthermore, there was a trend towards a higher level of compliance and a lower incidence of drug-related adverse events in the twice-daily compared with the three-times-daily treatment group.", "Children with acute otitis media (AOM), aged 2-12 years, were randomised to 10 days treatment with amoxycillin/clavulanate (A/C) 70/10 mg/kg/day given b.i.d. (231 patients) or to A/C 60/15 mg/kg/day given t.i.d. (232 patients). Clinical success rates at end of therapy (10-17 days) were 91.8% for the b.i.d. group and 90.5% for the t.i.d. group and at follow-up (28-42 days) were 80.1% for the b.i.d. group and 77.6% for the t.i.d. group, indicating that the b.i.d. regimen was as effective as the t.i.d. regimen. There was no statistically significant difference in incidence of adverse experiences between the two groups. The overall incidence of protocol defined diarrhoea assessed from diary booklets was low, with a lower incidence in the b.i.d. group (6.7%) than in the t.i.d. group (10.3%). Significantly more patients in the b.i.d. group (83.1%) than in the t.i.d. group (72.8%) had at least 80% compliance over a 7-10 day treatment period. A/C given twice or three-times daily was highly effective in the treatment of AOM in children. The two regimens showed equivalent clinical efficacy, both were well tolerated, and there was evidence of improved compliance with the b.i.d. regimen." ]	This review showed insufficient evidence to judge whether once or twice daily doses of amoxicillin, with or without clavulanate, were comparable with three or four daily doses for the treatment of AOM. The evidence appears to be biased and therefore no firm conclusions can be drawn.
CD001099	[ "1913123", "2107563", "1579252", "11797982" ]	[ "Randomized trial of intra-arterial recombinant tissue plasminogen activator, intravenous recombinant tissue plasminogen activator and intra-arterial streptokinase in peripheral arterial thrombolysis.", "Recombinant tissue-type plasminogen activator versus urokinase in peripheral arterial and graft occlusions: a randomized trial.", "Intravenous recombinant tissue plasminogen activator in acute carotid artery territory stroke.", "Recombinant tissue plasminogen activator versus urokinase for local thrombolysis of femoropopliteal occlusions: a prospective, randomized multicenter trial." ]	[ "Sixty patients were recruited into a randomized parallel group comparison of three thrombolytic regimens for acute or subacute peripheral arterial thrombosis. There were no significant differences in age, duration of history, length of occlusion or presence of neurosensory deficit between the groups. Initially successful lysis was significantly greater with intra-arterial (IA) recombinant tissue plasminogen activator (rt-PA) than with either streptokinase (Sk) (P less than 0.04) or intravenous (IV) rt-PA (P less than 0.01). The duration of therapy varied from a median of 35 h with IA rt-PA to 40 h with Sk (P greater than 0.5). The median (confidence interval) increase in ankle:brachial pressure index following IA rt-PA of 0.57 (0.33-0.82) was significantly higher than for either Sk of 0.24 (0-0.57) or for IV rt-PA of 0.18 (0-0.41). Limb salvage at 30 days was achieved in 80, 60 and 45 per cent respectively for IA rt-PA, Sk and IV rt-PA. Haemorrhagic complications occurred in six patients following Sk and in 13 following IV rt-PA; only one minor haemorrhage occurred following a catheter perforation in a patient who received IA rt-PA (P less than 0.05). IA rt-PA provides a more effective, safer fibrinolytic regimen than conventional therapy with Sk. IV rt-PA has not been as successful and carries a significantly higher risk of haemorrhagic complications.", "A randomized prospective trial was undertaken to compare intraarterial administration of recombinant human tissue-type plasminogen activator (rt-PA) with urokinase (UK) in 32 patients with peripheral arterial or bypass graft occlusions. Sixteen patients were randomized to receive rt-PA and 16 to receive UK. The rt-PA dose was administered as a 10-mg bolus into the thrombus, followed by 5 mg/h for up to 24 hours. The UK dose was administered as a 60,000 IU bolus into the thrombus, followed by 240,000 IU/h for 2 hours, 120,000 IU/h for 2 hours, and 60,000 IU/h for up to 20 hours. Serial arteriograms were obtained at baseline and at 4, 8 or 16, and 24 hours. The endpoint was defined as 95% of greater clot lysis. The cumulative numbers of patients with successful thrombolysis (rt-PA vs UK) were four vs none at 4 hours, seven vs one at 8 hours, seven vs three at 16 hours, and eight vs six at 24 hours. Lysis occurred more rapidly in the rt-PA group (P = .04). Major bleeding complications occurred in five rt-PA patients and two UK patients (P = .39). At 24 hours, fibrinogen levels were significantly lower in the rt-PA group than in the UK group (P = .01). There was no apparent difference in 30-day clinical success.", "To determine the effect of intravenous recombinant tissue plasminogen activator (rt-PA) on vascular and neurologic outcomes, we enrolled 31 patients with acute carotid artery-territory ischemic stroke within 6 hours from symptom onset in a randomized, double-blind, placebo-controlled study. We gave either rt-PA (duteplase at the dose of 20 or 30 mega-international units [MIU]) or placebo intravenously for 60 minutes in patients randomly assigned to the three groups. A comparison between the baseline and postinfusion angiograms showed that complete or partial reperfusion occurred in 50% (5/10) of patients treated with 30 MIU rt-PA, 44% (4/9) of those treated with 20 MIU rt-PA, and 17% (2/12) in the control group. In patients with middle cerebral artery occlusions, reperfusion occurred in 71% (5/7) of the 30-MIU group, in 67% (4/6) of the 20-MIU group, and in 13% (1/8) of the control group. Patients treated with 30 MIU rt-PA showed a significantly early and better clinical improvement, as measured by the neurologic scale, than did those treated with placebo. Parenchymal hemorrhage occurred in one patient in each group, and frequency of clinically insignificant hemorrhagic infarction was comparable among the treatment groups. No major systemic complications occurred in any group. These results support the efficacy of intravenous infusion of rt-PA soon after the onset of stroke in producing rapid thrombolysis and neurologic recovery; it may be of particular value in patients with thromboembolic occlusion in the middle cerebral artery.", "To report the outcome of a prospective, randomized, open multicenter trial comparing (1) the effects of local thrombolysis with recombinant tissue plasminogen activator (rtPA) or urokinase (UK) and (2) 2 administration techniques.\n Two hundred thirty-four patients with thromboembolic occlusions in 223 native femoral or popliteal arteries (95%) and 11 bypass grafts (5%) were randomized to rtPA (n = 124) or UK (n = 110) administered either through an endhole catheter (Hess technique) in 81 patients or a microporous balloon catheter (Schneider technique) in 153 patients. When lysis was incomplete, additional catheter interventions were applied to achieve patency. Results were analyzed by fluoroscopy during intervention and by angiography evaluated by independent experts blinded to the methods applied.\n The only significant difference between rtPA and UK was found at the end of lysis using the Hess technique. Complete reperfusion (TIMI grade 3) was produced in 60% of patients by rtPA versus 37% by UK (p = 0.045). By both techniques TIMI grade 3 was achieved in 62% with rtPA and in 50% with UK (p = 0.18). Independent of delivery technique, thrombolytic agent, or additional catheter interventions, TIMI grade 3 was achieved in 81% and angiographic patency in 88%. Primary patency at 6 months was 66%, which was increased by secondary interventions to 75%. Major amputations were performed in 6%, all in patients with initial Fontaine stage III/IV ischemia.\n With local thrombolysis alone, rtPA appears to be more effective than UK; however, additional catheter interventions further improved patency, abolishing the difference between the lytic agents." ]	There is some evidence to suggest that intra-arterial rt-PA is more effective than intra-arterial streptokinase or intravenous rt-PA in improving vessel patency in people with peripheral arterial occlusion. There was no evidence that rt-PA was more effective than urokinase for patients with peripheral arterial occlusion and some evidence that initial lysis may be more rapid with rt-PA, depending on the regime. Incidences of haemorrhagic complications were not statistically significantly greater with rt-PA than with other regimes. However, all of the findings come from small studies and a general paucity of results means that it is not possible to draw clear conclusions.
CD005648	[ "16296913", "16047154" ]	[ "Homeopathy for attention-deficit/hyperactivity disorder: a pilot randomized-controlled trial.", "Homeopathic treatment of children with attention deficit hyperactivity disorder: a randomised, double blind, placebo controlled crossover trial." ]	[ "The aim of this study was to carry out a preliminary trial evaluating the effectiveness of homeopathy in the treatment of attention-deficit/hyperactivity disorder (ADHD).\n This work was a randomized, double-blind, placebo-controlled trial.\n This study was conducted in a private homeopathic clinic in the Seattle metropolitan area.\n Subjects included children 6-12 years of age meeting Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria for ADHD.\n Forty-three subjects were randomized to receive a homeopathic consultation and either an individualized homeopathic remedy or placebo. Patients were seen by homeopathic physicians every 6 weeks for 18 weeks.\n Outcome measures included the Conner's Global Index-Parent, Conner's Global Index- Teacher, Conner's Parent Rating Scale-Brief, Continuous Performance Test, and the Clinical Global Impression Scale. Results: There were no statistically significant differences between homeopathic remedy and placebo groups on the primary or secondary outcome variables. However, there were statistically and clinically significant improvements in both groups on many of the outcome measures.\n This pilot study provides no evidence to support a therapeutic effect of individually selected homeopathic remedies in children with ADHD. A therapeutic effect of the homeopathic encounter is suggested and warrants further evaluation. Future studies should be carried out over a longer period of time and should include a control group that does not receive the homeopathic consultation. Comparison to conventional stimulant medication for ADHD also should be considered.", "An increasing number of parents turn to homeopathy for treatment of their hyperactive child. Two publications, a randomised, partially blinded trial and a clinical observation study, conclude that homeopathy has positive effects in patients with attention deficit hyperactivity disorder (ADHD). The aim of this study was to obtain scientific evidence of the effectiveness of homeopathy in ADHD. A total of 83 children aged 6-16 years, with ADHD diagnosed using the Diagnostic and Statistical Manual of Mental Disorders-IV criteria, were recruited. Prior to the randomised, double blind, placebo controlled crossover study, they were treated with individually prescribed homeopathic medications. 62 patients, who achieved an improvement of 50% in the Conners' Global Index (CGI), participated in the trial. Thirteen patients did not fulfill this eligibility criterion (CGI). The responders were split into two groups and received either verum for 6 weeks followed by placebo for 6 weeks (arm A), or vice-versa (arm B). At the beginning of the trial and after each crossover period, parents reported the CGI and patients underwent neuropsychological testing. The CGI rating was evaluated again at the end of each crossover period and twice in long-term follow-up. At entry to the crossover trial, cognitive performance such as visual global perception, impulsivity and divided attention, had improved significantly under open label treatment (P<0.0001). During the crossover trial, CGI parent-ratings were significantly lower under verum (average 1.67 points) than under placebo (P =0.0479). Long-term CGI improvement reached 12 points (63%, P <0.0001).\n The trial suggests scientific evidence of the effectiveness of homeopathy in the treatment of attention deficit hyperactivity disorder, particularly in the areas of behavioural and cognitive functions." ]	There is currently little evidence for the efficacy of homeopathy for the treatment of ADHD. Development of optimal treatment protocols is recommended prior to further randomised controlled trials being undertaken.
CD003391	[ "2405806", "1882999", "9299800", "9090340", "8120155", "3134343", "14992983", "1550466", "3511877", "1728190", "10910801", "11386493", "8124322", "2011615", "11459384", "11195257" ]	[ "A comparison study of antidepressants and structured intensive group psychotherapy in the treatment of bulimia nervosa.", "Long-term outcome of antidepressant treatment for bulimia nervosa.", "A randomized controlled trial of fluoxetine and cognitive behavioral therapy for bulimia nervosa: short-term outcome.", "Medication and psychotherapy in the treatment of bulimia nervosa.", "Is there a role for selective monoamine oxidase inhibitor therapy in bulimia nervosa? A placebo-controlled trial of brofaromine.", "Treatment of bulimia with bupropion: a multicenter controlled trial.", "Treatment of bulimia nervosa in a primary care setting.", "Fluoxetine in the treatment of bulimia nervosa. A multicenter, placebo-controlled, double-blind trial. Fluoxetine Bulimia Nervosa Collaborative Study Group.", "Anorexia nervosa. Treatment efficacy of cyproheptadine and amitriptyline.", "Pharmacologic and cognitive-behavioral treatment for bulimia nervosa: a controlled comparison.", "Fluoxetine for bulimia nervosa following poor response to psychotherapy.", "The relative efficacy of fluoxetine and manual-based self-help in the treatment of outpatients with bulimia nervosa.", "A double-blind placebo-controlled comparison of phenelzine and imipramine in the treatment of bulimia in atypical depressives.", "Fluoxetine versus placebo: a double-blind study with bulimic inpatients undergoing intensive psychotherapy.", "Cognitive therapy, nutritional therapy and their combination in the treatment of bulimia nervosa.", "Efficacy and tolerability of moclobemide in bulimia nervosa: a placebo-controlled trial." ]	[ "Previous research on the treatment of outpatients with bulimia nervosa has focused on two treatment strategies: (1) drug therapy, primarily using tricyclic antidepressants, and (2) psychotherapy, often employing behavioral and cognitive behavioral techniques. We report here the short-term treatment outcome of a 12-week comparison trial of bulimic outpatients who were randomly assigned to one of four treatment cells: (1) imipramine hydrochloride treatment, (2) placebo treatment, (3) imipramine treatment combined with intensive group psychotherapy, and (4) placebo treatment combined with intensive group psychotherapy. All three active treatment cells resulted in significant reductions in target-eating behaviors and in a significant improvement in mood relative to placebo treatment. However, the results also suggested that the amount of improvement obtained with the intensive group psychotherapy component was superior to that obtained with antidepressant treatment alone. The addition of antidepressant treatment to the intensive group psychotherapy component did not significantly improve outcome over intensive group psychotherapy combined with placebo treatment in terms of eating behavior, but did result in more improvement in the symptoms of depression and anxiety.", "The purpose of this study was 1) to replicate previous work indicating that antidepressant medication is superior to placebo in the treatment of bulimia nervosa and 2) to assess the long-term efficacy of this form of treatment.\n Eighty patients entered a three-phase treatment protocol. An 8-week double-blind initiation phase was used to compare the effects of desipramine and placebo. Patients who responded satisfactorily to desipramine entered a 16-week maintenance phase. Patients who remained well were then randomly assigned to either desipramine or placebo for 6 additional months (discontinuation phase). The primary outcome measure was binge frequency, which was assessed weekly by self-report diaries.\n In the initiation phase the superiority of desipramine over placebo in reducing binge frequency was demonstrated. Patients treated with desipramine had a mean reduction in binge frequency of 47% at termination, whereas patients taking placebo experienced a mean increase of 7%. Less than half of the patients treated with desipramine met the criteria for entering the maintenance phase, and 29% of the patients entering that phase relapsed in the following 4 months. There were not enough patients in the discontinuation phase to permit clear conclusions about the need for continued antidepressant medication after 6 months of treatment.\n The study documents a beneficial effect of desipramine in the treatment of bulimia nervosa when compared to placebo. However, limited improvement and considerable relapse with continued treatment suggest serious limitations to the long-term efficacy of a single antidepressant trial in treating bulimia nervosa.", "This study compared and combined fluoxetine and individual cognitive behavioral therapy in the treatment of bulimia nervosa. Participants were 76 women who sought treatment at the Eating Disorders Program of the Toronto Hospital and who met DSM-III-R criteria for bulimia nervosa. Subjects were randomly assigned to receive fluoxetine alone, cognitive behavior therapy alone, or the two in combination and were treated over 16 weeks. Short-term outcome revealed that all three treatment conditions were associated with clinical improvement across a wide range of parameters. The combination of pharmacotherapy and psychotherapy was superior to pharmacotherapy alone on specific parameters and there was no statistically significant advantage to the combination over psychotherapy alone. Limitations to the study include the absence of a placebo pill group and a waiting list control group as well as a substantial dropout rate across all three treatment conditions.", "Two treatments for bulimia nervosa have emerged as having established efficacy: cognitive-behavioral therapy and antidepressant medication. This study sought to address 1) how the efficacy of a psychodynamically oriented supportive psychotherapy compared to that of cognitive-behavioral therapy; 2) whether a two-stage medication intervention, in which a second antidepressant (fluoxetine) was employed if the first (desipramine) was either ineffective or poorly tolerated, added to the benefit of psychological treatment; and 3) if the combination of medication and psychological treatment was superior to a course of medication alone.\n A total of 120 women with bulimia nervosa participated in a randomized, placebo-controlled trial.\n Cognitive-behavioral therapy was superior to supportive psychotherapy in reducing behavioral symptoms of bulimia nervosa (binge eating and vomiting). Patients receiving medication in combination with psychological treatment experienced greater improvement in binge eating and depression than did patients receiving placebo and psychological treatment. In addition, cognitive-behavioral therapy plus medication was superior to medication alone, but supportive psychotherapy plus medication was not.\n At present, cognitive-behavioral therapy is the psychological treatment of choice for bulimia nervosa. A two-stage medication intervention using fluoxetine adds modestly to the benefit of psychological treatment.", "Pharmacologic and cognitive behavioral therapies have been advocated in the treatment of bulimia nervosa (BN). Brofaromine, a selective and reversible inhibitor of monoamine oxidase-A was selected for a double-blind, placebo-controlled evaluation because of previous demonstrated monoamine oxidase inhibitor efficacy in BN and because of its safer adverse reaction profile. Thirty-six female patients who met DSM-III-R criteria for BN were randomly assigned to the drug group (N = 19) or to the placebo group (N = 17) for an 8-week outpatient trial. Brofaromine produced a significant effect in decreasing episodes of vomiting throughout the trial, although comparable reductions in episodes of binge eating were found in both groups. Also, there were no advantages of drug over placebo on improvements in attitudinal measures and shape or on self-report ratings of depression and anxiety. However, a significant proportion of the subjects on brofaromine lost weight when compared with the placebo group. Methodologic issues including subjective assessment measures, placebo response rates, and the elucidation of responder subgroups are discussed.", "In a placebo-controlled, double-blind study of the unique antidepressant agent bupropion in the treatment of nondepressed subjects with bulimia (bupropion group, N = 55; placebo group, N = 26), we found the drug significantly superior to placebo in reducing episodes of binge eating and purging. In general, side effects with bupropion were minimal. However, four subjects experienced grand mal seizures during treatment with bupropion, a frequency of seizures far higher than observed in previous studies with this drug. Pending a satisfactory explanation for the occurrence of these seizures, we recommend that bupropion not be administered alone to bulimic patients.", "The authors' goal was to determine whether treatments known to be effective for bulimia nervosa in specialized treatment centers can be used successfully in primary health care settings. They examined the benefits of two treatments for bulimia: 1) fluoxetine, an antidepressant medication, and 2) guided self-help, an adaptation of cognitive behavior therapy.\n Ninety-one female patients in two primary care settings were randomly assigned to receive fluoxetine alone, placebo alone, fluoxetine plus guided self-help, or placebo and guided self-help.\n The majority of the patients did not complete the treatment trial; many patients found the treatment program too demanding, but others indicated it was not sufficiently intensive. Patients assigned to fluoxetine attended more physician visits, exhibited a greater reduction in binge eating and vomiting, and had a greater improvement in psychological symptoms than those assigned to placebo. There was no evidence of benefit from guided self-help.\n The treatment of patients with bulimia nervosa in a primary care setting is hampered by a high dropout rate. Guided self-help, a psychological treatment based on cognitive behavior therapy, appears ineffective, but treatment with fluoxetine is associated with better retention and substantial symptomatic improvement.", "Bulimia nervosa represents a serious public health problem in the United States. We performed an 8-week, double-blind trial comparing fluoxetine hydrochloride (60 and 20 mg/d) with placebo in 387 bulimic women treated on an outpatient basis. Fluoxetine at 60 mg/d proved superior to placebo in decreasing the frequency of weekly binge-eating and vomiting episodes at end point. Fluoxetine at 20 mg/d produced an effect between that of the 60-mg/d dosage and that of placebo. Depression, carbohydrate craving, and pathologic eating attitudes and behaviors also improved significantly with fluoxetine, with the higher dosage again showing a more robust effect than the lower dosage. Several adverse events (ie, insomnia, nausea, asthenia, and tremor) occurred significantly more frequently with fluoxetine (60 or 20 mg/d) than with placebo. However, there was no statistically significant difference among treatment groups in the proportion of patients discontinuing the study because of adverse events.", "Patients with anorexia nervosa have concurrent problems of emaciation and depression. Therefore, treatment with medications affecting both weight gain and depression seemed reasonable. Seventy-two anorectic patients were randomly assigned in a double-blind study to receive cyproheptadine hydrochloride, a weight-inducing drug, amitriptyline hydrochloride, a tricyclic antidepressant, or placebo. Overall, cyproheptadine had a marginal effect on decreasing the number of days necessary to achieve a normal weight. There was a differential drug effect present in the bulimic subgroups of the anorectic patients: cyproheptadine significantly increased treatment efficiency for the nonbulimic patients and significantly impaired treatment efficiency for the bulimic patients when compared with the amitriptyline- and placebo-treated groups. The differential cyproheptadine effect on the anorectic bulimic subgroups is the first pharmacologic evidence of the validity of these subgroups. Cyproheptadine had an anti-depressant effect demonstrated by a significant decrease in the Hamilton depression ratings.", "This study examined the relative effectiveness of desipramine, cognitive-behavioral therapy, and their combination in the treatment of bulimia nervosa, together with the effects of withdrawing medication after two different lengths of treatment.\n Seventy-one patients meeting DSM-III-R criteria for bulimia nervosa, recruited from an eating disorders clinic or by advertisements, were assigned at random to one of five groups: desipramine (withdrawn at 16 or 24 weeks), combined treatment (medication withdrawn at 16 or 24 weeks), and cognitive-behavioral therapy (15 sessions). All treatments were conducted individually in an outpatient clinic. The primary outcome measures were binge eating and purging rates assessed at pretreatment, 16, 24, and 32 weeks. The results were analyzed as three groups (medication, cognitive-behavioral therapy, and combined treatment) at 16 weeks and as five groups at subsequent assessments.\n At 16 weeks, both cognitive-behavioral therapy and the combined treatment were superior to medication given for 16 weeks in reducing binge eating and purging. At 32 weeks, however, only the combined 24-week treatment was superior to medication given for 16 weeks. The combined treatment was also more effective in reducing dietary preoccupation and hunger. Continuing cognitive-behavioral therapy appeared to prevent relapse in patients withdrawn from medication at 16 weeks.\n Overall, the results favor the use of a combination of medication and cognitive-behavioral therapy in the treatment of bulimia nervosa, with medication continued for at least 24 weeks.", "This was an investigation of whether treatment with fluoxetine is useful for individuals with bulimia nervosa who do not respond to psychotherapy or relapse afterward.\n Twenty-two patients with bulimia nervosa who had not responded to, or had relapsed following, a course of cognitive behavior therapy or interpersonal psychotherapy were randomly assigned to receive placebo (N=9) or fluoxetine (60 mg/day, N=13) for 8 weeks.\n The median frequency of binge eating in the previous 28 days declined from 22 to four episodes in the fluoxetine group but increased from 15 to 18 episodes in the placebo group. Similarly, purging frequency in the previous 28 days declined from 30 to six episodes in the fluoxetine group but increased from 15 to 38 episodes in the placebo group.\n Fluoxetine may be a useful intervention for patients with bulimia nervosa who have not responded adequately to psychological treatment.", "A randomized, placebo-controlled study was conducted examining the singular and combined effects of fluoxetine and a self-help manual on suppressing bulimic behaviors in women with bulimia nervosa. A total of 91 adult women with bulimia nervosa were randomly assigned to one of four conditions: placebo only, fluoxetine only, placebo and a self-help manual, or fluoxetine and a self-help manual. Subjects were treated for 16 weeks. Primary outcome measures included self-reports of bulimic behaviors. Fluoxetine and a self-help manual were found to be effective in reducing the frequency of vomiting episodes and in improving the response rates for vomiting and binge-eating episodes. Furthermore, both factors were shown to be acting additively on the primary and secondary efficacy measures in this study. Results are discussed in relation to previous research and the implications for treatment of bulimia nervosa.", "Although antidepressants have been found to be superior to placebo in 12 of 14 studies, the relationship between improvement in the depressive diathesis and bulimia is unclear. In this study, the efficacy of placebo, imipramine, and phenelzine is examined in patients comorbid for atypical depression and bulimia. Greater improvement was observed for both depressive and bulimic symptoms with phenelzine than with either imipramine or placebo. Consistent with its poor antidepressant effects in atypical depression, imipramine seemed to have minimal efficacy for the bulimic symptoms of atypical depressives. These data suggest that the presence of bulimia does not alter the treatment response of atypically depressed patients. Furthermore, the data may suggest a link between depression and bulimia in atypical depressives. Demonstrating a statistical difference with a small sample suggests the effect size is robust, however conclusions are limited by a small sample size.", "In a double-blind trial 40 patients with bulimia nervosa according to DSM III-R criteria were randomly assigned either to a 60 mg fluoxetine group or to a placebo control group. Fluoxetine or placebo was given over a period of 35 days. Parallel to the drug trial, patients participated in an intensive inpatient behavioral psychotherapy program. There were no dropouts at all in the study. Fluoxetine was well tolerated and had only minor adverse effects. In self-ratings and expert ratings concerning attitudes towards eating, eating behavior, and general psychopathology, significant improvements over time were observed in both groups. Using analysis of variance (ANOVA), however, there were no statistically significant \"group by time\" differences. Results show that the intensive inpatient-care and psychotherapy program was highly effective in changing eating behavior and attitudes as well as general psychopathology. Fluoxetine showed a significant reduction in body weight, especially during the first three weeks of fluoxetine treatment. It was not possible to demonstrate a statistically significant improvement in eating attitudes, eating behavior, and general psychopathology beyond that elicited by intensive inpatient psychotherapy and general inpatient care. These results can possibly be explained by the existence of a \"ceiling effect\".", "This study compared the effectiveness of cognitive therapy (CT), nutritional therapy (NT), the combination of cognitive and nutritional therapy (CNT), against a control condition of support group (SG) in the treatment of bulimia nervosa.\n One hundred female out-patients who fulfilled DSM-III-R criteria for bulimia nervosa were randomized to the four treatment groups. NT and CT were designed to cover different areas with minimal overlap, and CNT provided all of the features of both of these treatments. The control condition was conducted in a group self-help format. Each of the treatments lasted 14 weeks.\n All three active treatments as well as SG produced significant decreases in binge/vomit episodes. Intent-to-treat analysis found CNT and CT to be significantly more effective than SG in retaining subjects in treatment and completion of study, as well as in producing greater improvements in dysfunctional attitudes and self-control. CNT was superior to SG in achieving abstinence from bulimic behaviour. NT was superior to SG only in increase of self-control. Logistic regression found that the cognitive component, whether given alone or in conjunction with NT, and higher pre-treatment self-control scores were significant predictors for both completion of study and abstinence.\n CT (either alone, or in combination with nutritional therapy) remains the treatment of choice for bulimia nervosa. A treatment escalation approach should be tested for the treatment of bulimia with the more intensive and less widely available CT (with or without nutritional counselling) offered after patients have failed the less intensive and more widely available support group treatment.", "A 6-week double-blind placebo-controlled trial was carried out to examine the efficacy and tolerability of moclobemide, a monoamine oxidase type A selective and reversible inhibitor, in the treatment of bulimia nervosa. Patients were admitted to the study even if they were unable to adhere to a tyramine-free diet. Fifty-two normal-weight women (age range 18-40 years) suffering from bulimia nervosa (DSM-IV criteria) completed the trial. Particular emphasis was placed on evaluating the incidence of hypertension and other side-effects in chronically treated patients. At the usual antidepressant dose of 600 mg, moclobemide was not significantly superior to placebo in the reducing the weekly number of binge eating episodes or in improving several measures of eating attitudes and behaviour (BITE, EDI, TFEQ) in normal-weight bulimia nervosa. The dropout rate was relatively low (29%), and the side-effects were limited and equally distributed between the two treatment groups. No patient experienced a hypertensive crisis during the study and no serious side-effect was detected. The study indicates that moclobemide 600 mg pro die is not efficacious in bulimia nervosa, but it can be safely administered, even to young subjects, at a very high risk of consuming large amounts of tyramine-rich foods without dietary restrictions." ]	The use of a single antidepressant agent was clinically effective for the treatment of bulimia nervosa when compared to placebo, with an overall greater remission rate but a higher rate of dropouts. No differential effect regarding efficacy and tolerability among the various classes of antidepressants could be demonstrated.
CD005493	[ "18499184", "15201783", "12447093", "19389019", "9704373", "19375091", "19145653" ]	[ "Refractory idiopathic urge urinary incontinence and botulinum A injection.", "Intravesical resiniferatoxin versus botulinum-A toxin injections for neurogenic detrusor overactivity: a prospective randomized study.", "BOTOX and physical therapy in the treatment of piriformis syndrome.", "Improvement in quality of life after botulinum toxin-A injections for idiopathic detrusor overactivity: results from a randomized double-blind placebo-controlled trial.", "A randomized, double-blind, prospective pilot study of botulinum toxin injection for refractory, unilateral, cervicothoracic, paraspinal, myofascial pain syndrome.", "Outcome of a randomized, double-blind, placebo controlled trial of botulinum A toxin for refractory overactive bladder.", "Randomized double-blind study of botulinum toxin type B for sialorrhea in ALS patients." ]	[ "We compared 200 U intradetrusor botulinum toxin A vs placebo in women with refractory idiopathic urge incontinence.\n This institutional review board approved, multicenter registered trial randomized women with refractory urge incontinence, detrusor overactivity incontinence and 6 or greater urge incontinence episodes in 3 days to botulinum toxin A or placebo at a 2:1 ratio. Refractory was defined as inadequate symptom control after 2 or more attempts at pharmacotherapy and 1 or more other first line therapies for detrusor overactivity incontinence. The primary outcome measure was time to failure, as evidenced by a Patient Global Impression of Improvement score of 4 or greater at least 2 months after injection, or changes in treatment (initiation or increase) at any time after injection. Safety data, including increased post-void residual volume, defined as more than 200 ml irrespective of symptoms, was obtained at specified time points.\n Approximately 60% of the women who received botulinum toxin A had a clinical response based on the Patient Global Impression of Improvement. The median duration of their responses was 373 days, significantly longer than the 62 days or less for placebo (p <0.0001). In the botulinum toxin A group increased post-void residual urine (12 of 28 women or 43%) and urinary tract infection in those with increased post-void residual urine (9 of 12 or 75%) exceeded expected ranges. Further injections were stopped after 43 patients were randomized, including 28 to botulinum toxin A and 15 to placebo.\n Local injection of 200 U botulinum toxin A was an effective and durable treatment for refractory overactive bladder. However, a transient post-void residual urine increase was experienced in 43% of patients. Botulinum toxin A for idiopathic overactive bladder is still under investigation.", "We investigated the effectiveness and safety of intravesical resiniferatoxin (Sigma Chemical Co., St. Louis, Missouri) and botulinum-A toxin injections into the detrusor muscle in a group of spinal cord injured patients with neurogenic detrusor overactivity unresponsive to conventional anticholinergic therapy.\n A total of 25 patients were randomly assigned to receive intravesically 0.6 microM resiniferatoxin in 50 ml of 0.9% NaCl or injections into the detrusor muscle of 300 units botulinum A-toxin diluted in 30 ml 0.9% NaCl. Clinical evaluation and urodynamics were performed at baseline, and at 6, 12 and 18 months after treatment.\n In both arms there was a significant decrease in catheterization and incontinent episodes, and a significant increase in first detrusor contraction and maximum bladder capacity at 6, 12 and 18-month followup. There were no local side effects with either treatment. Botulinum-A toxin induced a significant decrease in the frequency of daily incontinence episodes (p <0.05), a significant increase in first uninhibited detrusor contraction (p <0.01) in maximum bladder capacity (p <0.01), and a significant decrease in maximum pressure of uninhibited detrusor contractions (p <0.01) compared to resiniferatoxin at 6, 12 and 18-month followup.\n In spinal cord injured patients with refractory neurogenic detrusor overactivity, intravesical resiniferatoxin and botulinum-A toxin injections into the detrusor muscle provided beneficial clinical and urodynamic results with decreases in detrusor overactivity and restoration of urinary continence in a large proportion of patients. Botulinum-A toxin injections provided superior clinical and urodynamic benefits compared to those of intravesical resiniferatoxin.", "This study evaluates the efficacy of botulinum toxin A injections used in conjunction with physical therapy for the treatment of piriformis syndrome.\n This a double-blind, placebo controlled clinical trial using electrophysiologic criteria for patient selection and a visual analog scale to assess treatment efficacy in relieving pain.\n As measured on the visual analog scale, patients injected with botulinum toxin A experienced more relief from pain than patients receiving lidocaine with steroid (P < 0.05) and more relief than patients receiving placebo (P = 0.001).\n Injection with botulinum toxin A is an effective adjunct to physical therapy in the treatment of piriformis syndrome. H-reflex prolongation by flexion, adduction, and internal rotation (FAIR test) beyond 1.86 msec (3 SD) of the mean is a clinical indication of piriformis syndrome.", "OBJECTIVE To determine whether botulinum toxin-A (BTX-A) treatment has an effect on the quality of life (QoL) of patients with overactive bladder (OAB) refractory to anticholinergics. PATIENTS AND METHODS This was a single centre, randomized, double-blind, placebo-controlled trial. Participants were men and women with idiopathic detrusor overactivity (IDO). Participants were randomised to receive either 200 U of BTX-A (Botox(R), Allergan Inc., Irvine, CA, USA; n = 16) or placebo (n = 18) via a trigone-sparing flexible cystoscopic technique. QoL was assessed using the King's Health Questionnaire (KHQ) at baseline and at 4 and 12 weeks, after injection. At 12 weeks patients were 'unblinded' and a further open-label follow-up in the BTX-A group occurred at 24 weeks. The changes in the subdomains of the KHQ were assessed over the study period. RESULTS Overall QoL was significantly improved in the BTX-A treated patients compared with placebo in the blinded part of the study. When analysing the KHQ subdomains, 'Incontinence Impact', 'Emotions', 'Physical Limitations', 'Social Limitations' and 'Severity Measures' were significantly improved in those that received BTX-A compared with placebo. The 'Symptom Severity' domain was also significantly improved at 4 weeks but not at 12 weeks. At 12 weeks 'Role Limitations' also became statistically significant in favour of BTX-A. The open-label extension study suggested these benefits last for at least 24 weeks. CONCLUSIONS BTX-A bladder injections at 200 U appear to improve QoL in patients with OAB symptoms and IDO refractory to anticholinergics for at least 24 weeks. As well as the improvement seen in clinical parameters with this form of therapy, perhaps of more importance to the patient, is the improvement in QoL.", "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.", "We determined the effectiveness of cystoscopic administration of botulinum-A toxin compared to placebo for the treatment of urinary incontinence in subjects with idiopathic overactive bladder.\n Subjects were recruited from the Division of Urogynecology at the University of Rochester. Inclusion criteria were overactive bladder refractory to anticholinergic medications, multiple daily incontinence episodes and a 24-hour pad weight of 100 gm or greater. Subjects with low leak point pressures, increased post-void residual volume or neurological etiologies were excluded from study. Subjects were randomized to placebo or to 1 of 2 doses of botulinum-A toxin. The detrusor was injected at 8 to 10 sites above the trigone. Evaluations were performed at baseline, and at 3 and 6 weeks after injection, and included bladder diaries, pad weights, quality of life questionnaires and urodynamic studies.\n A total of 22 subjects participated in stage 1 of this 2-stage study. We report on the outcomes of stage 1 of this study. Because stage 2 is still ongoing and investigators remain blind to the doses of botulinum-A toxin, the 2 botulinum-A toxin groups were combined for this report. There were no differences in mean baseline measurements between the 2 groups. Statistically significant improvements in daily incontinence episodes, pads changed per day and quality of life questionnaires were seen in the botulinum-A toxin group with no changes in the placebo group. No change in nocturia, daily voiding frequency, peak flow or detrusor pressure was seen in either group. Of 15 subjects 4 (26%) receiving botulinum-A toxin had a post-void residual volume of 200 cc or greater and 1 subject required intermittent catheterization. Four subjects experienced a urinary tract infection, 2 (13%) in the botulinum-A toxin group and 2 (28%) in the placebo group (not significant).\n Botulinum-A toxin can significantly reduce urge urinary incontinence due to overactive bladder at 6 weeks. However, there is a risk of urinary retention requiring self-catheterization.", "Twenty ALS patients with sialorrhea refractory to medical therapy were enrolled in this double-blind, randomized study to receive either 2,500 U of botulinum toxin type B (BTxb) or placebo into the bilateral parotid and submandibular glands using electromyographic guidance. Patients who received BTxb reported a global impression of improvement of 82% at 2 weeks compared to 38% of those who received placebo (P < 0.05). This significant effect was sustained at 4 weeks. At 12 weeks, 50% of patients who received BTxb continued to report improvement compared to 14% of those who received placebo. There were no significant adverse events, including dysphagia, in the BTxb group, and there was no significant increase in the rate of decline of vital capacity." ]	Intravesical botulinum toxin appears to be an effective therapy for refractory OAB symptoms, but as yet little controlled trial data exist on benefits and safety compared with other interventions, or with placebo. Further robust data are required on long term outcomes, safety, and optimal dose of botulinum toxin for OAB.
CD005332	[ "11037083", "22108765", "12455427", "16495014", "8894955" ]	[ "Randomized controlled trial of cognitive behaviour therapy for repeated consultations for medically unexplained complaints: a feasibility study in Sri Lanka.", "Cognitive behavioral therapy for the treatment of juvenile fibromyalgia: a multisite, single-blind, randomized, controlled clinical trial.", "A randomized clinical trial of a tailored comprehensive care treatment program for temporomandibular disorders.", "Short- and long-term efficacy of brief cognitive-behavioral therapy for patients with chronic temporomandibular disorder pain: a randomized, controlled trial.", "Controlled trial of a brief cognitive-behavioural intervention in adolescent patients with depressive disorders." ]	[ "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.", "Juvenile fibromyalgia syndrome (FMS) is a chronic musculoskeletal pain disorder in children and adolescents for which there are no evidence-based treatments. The objective of this multisite, single-blind, randomized clinical trial was to test whether cognitive-behavioral therapy (CBT) was superior to fibromyalgia (FM) education in reducing functional disability, pain, and symptoms of depression in juvenile FMS.\n Participants were 114 adolescents (ages 11-18 years) with juvenile FMS. After receiving stable medications for 8 weeks, patients were randomized to either CBT or FM education and received 8 weekly individual sessions with a therapist and 2 booster sessions. Assessments were conducted at baseline, immediately following the 8-week treatment phase, and at 6-month followup.\n The majority of patients (87.7%) completed the trial per protocol. Intent-to-treat analyses showed that patients in both groups had significant reductions in functional disability, pain, and symptoms of depression at the end of the study, and CBT was significantly superior to FM education in reducing the primary outcome of functional disability (mean baseline to end-of-treatment difference between groups 5.39 [95% confidence interval 1.57, 9.22]). Reduction in symptoms of depression was clinically significant for both groups, with mean scores in the range of normal/nondepressed by the end of the study. Reduction in pain was not clinically significant for either group (<30% decrease in pain). There were no study-related adverse events.\n In this controlled trial, CBT was found to be a safe and effective treatment for reducing functional disability and symptoms of depression in adolescents with juvenile FMS.\n Copyright © 2012 by the American College of Rheumatology.", "To test the usefulness of tailoring cognitive-behavioral therapy (CBT) for patients with temporomandibular disorders (TMD) who demonstrated poor psychosocial adaptation to their TMD condition, independent of physical diagnosis.\n A randomized clinical trial compared a 6-session CBT intervention delivered in conjunction with the usual TMD treatment to the usual conservative treatment by TMD specialist dentists. For study inclusion, Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD), Axis II criteria, were used to target patients with elevated levels of TMD pain-related interference with daily activities, independent of physical diagnosis (i.e., Axis I).\n At the post-treatment assessment, about 4 months after the baseline evaluations, the comprehensive care group, when compared to the usual treatment group, showed significantly lower levels of characteristic pain intensity, significantly higher self-reported ability to control their TMD pain, and a strong trend (P = .07) toward lower pain-related interference in daily activities. From post-intervention to 1-year follow-up, all subjects showed improvement. At the 1-year follow-up, the comprehensive care group, while not losing any of its early gains, was not significantly different from the usual care group with regard to reported levels of pain, ability to control pain, and levels of interference in activities. For many of these psychosocially disabled TMD patients, pain and interference 1 year after treatment remained at the same or higher levels than those observed at baseline among a group of patients selected for a separate randomized clinical trial on the basis of better psychosocial adaptation.\n The 6-session CBT intervention for patients with heightened psychologic and psychosocial disability was effective in improving pain-related variables over the course of the CBT in conjunction with usual treatment, but was too brief an intervention to result in further improvement after the sessions ended. Patient ratings of treatment satisfaction and helfulness were high for both groups, but they were significantly higher for the comprehensive care group.", "We evaluated the short- and long-term efficacy of a brief cognitive-behavioral therapy (CBT) for chronic temporomandibular disorder (TMD) pain in a randomized controlled trial. TMD clinic patients were assigned randomly to four sessions of either CBT (n=79) or an education/attention control condition (n=79). Participants completed outcome (pain, activity interference, jaw function, and depression) and process (pain beliefs, catastrophizing, and coping) measures before randomization, and 3 (post-treatment), 6, and 12 months later. As compared with the control group, the CBT group showed significantly greater improvement across the follow-ups on each outcome, belief, and catastrophizing measure (intent-to-treat analyses). The CBT group also showed a greater increase in use of relaxation techniques to cope with pain, but not in use of other coping strategies assessed. On the primary outcome measure, activity interference, the proportion of patients who reported no interference at 12 months was nearly three times higher in the CBT group (35%) than in the control group (13%) (P=0.004). In addition, more CBT than control group patients had clinically meaningful improvement in pain intensity (50% versus 29% showed > or =50% decrease, P=0.01), masticatory jaw function (P<0.001), and depression (P=0.016) at 12 months (intent-to-treat analyses). The two groups improved equivalently on a measure of TMD knowledge. A brief CBT intervention improves one-year clinical outcomes of TMD clinic patients and these effects appear to result from specific ingredients of the CBT.", "Fifty-three child and adolescent psychiatric patients with depressive disorders were randomly allocated to brief cognitive-behaviour therapy (CBT) or to a control treatment, relaxation training. Forty-eight patients completed the treatment phase of the trial, which comprised 5-8 treatment sessions. Post-treatment assessments showed a clear advantage of CBT over relaxation on measures of both depression and overall outcome. However, there were no significant differences between the treatments on comorbid anxiety and conduct symptoms. At follow-up, the differences between the groups were reduced, partly because of a high relapse rate in the DTP group and partly because subjects in the relaxation group continued to recover." ]	Results from the small number of available RCTs suggest that SRIs and CBT may be useful in treating patients with BDD. The findings of these studies need to be replicated. In addition, future controlled studies in other samples, such as adolescents, and using other selective SRIs, as well as a range of psychological therapy approaches and modalities (alone and in combination), are essential in supplementing the sparse data currently available.
CD001352	[ "12677565", "8197563", "19887933", "17060756", "19854395", "18029237", "8988818", "19000234", "10707452", "15920210", "20067642", "18948801", "15349113", "17618805", "10166598", "10420346", "12368674", "18161613", "10376458", "17115429", "11434080", "3907971", "7853047", "8584545", "17122975", "15089956", "17522511" ]	[ "Randomized controlled trials in pediatric surgery: could we do better?", "Randomized controlled trials in surgery.", "Association between research sponsorship and study outcome in plastic surgery literature.", "Standards of reporting of randomized controlled trials in general surgery: can we do better?", "Quality of reporting in randomized trials published in high-quality surgical journals.", "The reporting quality of randomised controlled trials in surgery: a systematic review.", "Quality and retrieval of obstetrical anaesthesia randomized controlled trials.", "The quality of reporting of randomized controlled trials in solid organ transplantation.", "Handsearching the Journal of the Royal Naval Medical Service for Trials.", "The quality of randomized controlled trials in major anesthesiology journals.", "Reporting randomised clinical trials of analgesics after traumatic or orthopaedic surgery is inadequate: a systematic review.", "Surgeon volume does not predict outcomes in the setting of technical credentialing: results from a randomized trial in colon cancer.", "Teaching practicing surgeons critical appraisal skills with an Internet-based journal club: A randomized, controlled trial.", "Randomized controlled trial of virtual reality simulator training: transfer to live patients.", "Identification and analysis of randomised controlled trials in nursing: a preliminary study.", "Handsearching the Journal of the Royal Army Medical Corps for trials.", "Virtual reality training improves operating room performance: results of a randomized, double-blinded study.", "Quality of reporting of key methodological items of randomized controlled trials in clinical ophthalmic journals.", "Virtual reality training in laparoscopic surgery: a preliminary assessment of minimally invasive surgical trainer virtual reality (MIST VR).", "Examination of the analytic quality of behavioral health randomized clinical trials.", "Can evidence change the rate of back surgery? A randomized trial of community-based education.", "The retrieval of randomized clinical trials in liver disease from the medical literature. A comparison of MEDLARS and manual methods.", "Cumulative meta-analysis of clinical trials builds evidence for exemplary medical care.", "A comparison of patient teaching outcomes among postoperative coronary artery bypass graft (CABG) patients.", "Prospective randomized controlled trial of laparoscopic trainers for basic laparoscopic skills acquisition.", "Evidence-based postoperative pain management in nursing: is a randomized-controlled trial the most appropriate design?", "A prospective randomized controlled trial of multimodal perioperative management protocol in patients undergoing elective colorectal resection for cancer." ]	[ "Randomized controlled trials (RCTs) are accepted as the gold standard for assessing the effectiveness of clinical interventions but are rarely reported in pediatric surgery. Have RCTs submitted to the British Association of Paediatric Surgeons (BAPS) Annual Congress during the last 5 years been adequately designed and large enough to produce a valid result?\n Abstracts accepted by the Annual BAPS Congress meetings between 1996 and 2000 were examined in collaboration with a senior health services researcher. The quality of the design, methodology, statistical analysis and conclusions, and the adequacy of the sample size were assessed for all identifiable clinical RCTs.\n From 760 accepted abstracts, there were only 9 RCTs (1%) of clinical interventions. In only 4 trials was the relevant primary end-point specified at the outset of the study, and none documented the method of randomization. Only one abstract mentioned blinding with respect to the intervention or outcome measure. Sample sizes were inadequate to detect even large clinical differences. To date, only one of these RCTs has been published in an English-language, peer-reviewed journal.\n Clear guidelines exist for the conduct of RCTs, yet compliance with these standards was rarely documented in abstracts of pediatric surgical RCTs presented at BAPS. Sample sizes were inadequate. RCTs in pediatric surgery are difficult to perform, but the specialty would benefit from well-designed, carefully conducted, multicentre, clinical RCTs to advance evidence-based practice.\n Copyright 2003, Elsevier Science (USA). All rights reserved.", "The objective was to determine the number of randomized controlled trials (RCT) performed by surgeons, published in surgical journals, or comprising a surgical arm and to assess their characteristics and overall quality.\n RCT in general surgery (including gastrointestinal, breast, surgical oncology, vascular, critical care, and trauma) published in 1990 were retrieved by MEDLINE and analyzed to determine the funding agency, type of therapy, area of surgery, journal published, country of origin, number of centers, and whether a surgeon was the principal author. The completeness of the MEDLINE search was compared to a manual search of the literature. All RCT were assessed with Chalmers' qualitative score.\n MEDLINE retrieved 202 surgical RCT (46% of those retrieved by a manual search) with a mean score of 0.40 +/- 0.13. However, surgical RCT were performed by surgeons in only one third of trials, compared surgical therapies in only one quarter of trials, and were published in surgical journals in less than one third of trials. Only 22% of surgical RCT were funded by peer reviewed granting agencies. The strongest variables determining the quality of surgical RCT were the type of therapy tested (p = 0.0001), the type of journal published (p = 0.006), and the area of general surgery (p = 0.007).\n Although surgical RCT are being performed, there are a relatively low proportion and standard of RCT performed by surgeons as the principal author, published in surgical journals, and comparing surgical therapies. This may reflect a lack of expertise by surgeons in clinical trials, lack of funding for surgical trials, methodologic problems peculiar to surgical trials, or a need for adoption of other research designs to assess surgical therapies.", "Financial and other competing interests have recently received increasing attention. In particular clinical research in plastic surgery attracts for-profit organizations, thus, explaining the increasing number of financial sponsorships. However, research articles often lack sufficient description of study design as well as disclosure of the source of funding. Furthermore, debate exists whether industry funding influences research findings and is leading to pro-industry results. A hand search was conducted identifying all randomized controlled (RCT) and controlled clinical trials (CCT) in 4 plastic surgery journals (Plastic and Reconstructive Surgery, British Journal of Plastic Surgery, Annals of Plastic Surgery, and Aesthetic Plastic Surgery) between 1990 and 2005. Subsequently, the influence of financial support on study outcome was analyzed. A total of 10,476 original articles were analyzed, resulting in the identification of 346 clinical trials which meet the Cochrane criteria for RCTs and CCTs. One hundred eighty-three trials and 163 studies were found to be RCTs and CCTs, respectively. Hereof, only 70 trials (20.2%) reported on grant support. Of these, 42 trials (60%) were supported by the industry. Depending on the topic addressed marked differences were detected regarding grant support. Studies with a focus on reconstructive plastic surgery were supported by the industry and by public institutions in almost equal shares (18 trials vs. 15 trials), whereas aesthetic surgical topics were predominantly funded by the industry (13 trials vs. 6 trials). Industry-funded trials reported more often statistically significant differences between treatment arms (28 trials vs. 16 trials). Authors' conclusions were found to be positively associated with financial competing interests. However, trial funding is rarely declared in the plastic surgery literature. Thus, the quality of reporting needs to be improved to be able to investigate these relationships in greater detail and draw more representative conclusions.", "To evaluate the quality of reporting of surgical randomized controlled trials published in surgical and general medical journals using Jadad score, allocation concealment, and adherence to CONSORT guidelines and to identify factors associated with good quality.\n Randomized controlled trials (RCTs) provide the best evidence about the relative effectiveness of different interventions. Improper methodology and reporting of RCTs can lead to erroneous conclusions about treatment effects, which may mislead decision-making in health care at all levels.\n Information was obtained on RCTs published in 6 general surgical and 4 general medical journals in the year 2003. The quality of reporting of RCTs was assessed under masked conditions using allocation concealment, Jadad score, and a CONSORT checklist devised for the purpose.\n Of the 69 RCTs analyzed, only 37.7% had a Jadad score of > or =3, and only 13% of the trials clearly explained allocation concealment. The modified CONSORT score of surgical trials reported in medical journals was significantly higher than those reported in surgical journals (Mann-Whitney U test, P < 0.001). Overall, the modified CONSORT score was higher in studies with higher author numbers (P = 0.03), multicenter studies (P = 0.002), and studies with a declared funding source (P = 0.022).\n The overall quality of reporting of surgical RCTs was suboptimal. There is a need for improving awareness of the CONSORT statement among authors, reviewers, and editors of surgical journals and better quality control measures for trial reporting and methodology.", "Randomized controlled trials (RCTs) in surgery can provide valuable evidence of the efficacy of interventions if they are well-designed, appropriately executed, and adequately reported. Adequate reporting of methodology in surgical RCTs is known to be poor, and adverse-event reporting in surgical research is inconsistent. The Consolidated Standards of Reporting Trials (CONSORT) statement is a framework to help authors report their findings in a transparent manner. Extensions to the CONSORT statement have been published recently to address deficiencies in adverse-event reporting and in reporting of specific criteria related to nonpharmacologic treatments. The aim of this study was to assess the quality of reporting of trial methodology and adverse events in a sample of general surgical RCTs published in high-quality surgical journals using the criteria specified in the CONSORT statements.\n We used impact factor to identify the top three ranked surgical journals in 2004. We then obtained information on all RCTs published in these journals in the 2005 calendar year. We assessed quality of reporting using Jadad score, compared the quality of RCTs from CONSORT-endorsing journals with nonendorsers, and assessed the number of RCTs adequately reporting key generic methodologic, adverse-event-related, and specific nonpharmacologic criteria.\n Of 42 RCTs analyzed, only 40% (17 of 42) had a Jadad score > or = 3. There was no significant difference in the number of high-quality RCTs published in CONSORT-endorsing journals compared with nonendorsers (p = 0.3). The median percentage of RCTs adequately reporting generic methodologic, adverse-event-related, and specific nonpharmacologic criteria was 32.5%, 17%, and 36.5%, respectively.\n Quality of reporting of generic methodologic, adverse-event-related, and specific nonpharmacologic criteria in surgical RCTs is poor. Increased attention to quality of reporting of surgical RCTs is required if studies are to meet published criteria.", "In order to examine the reporting quality of urological RCTs, the initial objectives of this study were to evaluate the degree to which RCTs involving urological surgical techniques (as the intervention) published in the years 2000-2003 complied with the CONSORT statement, and to assess trends and patterns of compliance. Following our initial findings in urology, we extended the methodology to a number of other specialties to assess whether our findings in urology could be generalised to other surgical disciplines.\n The Royal Society of Medicine (RSM) Library was commissioned to search the Medline and Cochrane databases for RCTs in compliance with the study inclusion criteria below. Additional analyses of five other specialties (non-urological trials: cardiovascular, gastrointestinal, hepatic, orthopaedic and vascular) were also made. For the non-urological trials, 15 English language trials (from each specialty) were randomly picked from a blast search conducted by the RSM for the year 2003. The RCTs were given a score out of 22, reflecting how many of the 22 CONSORT items were complied with (with each item being given equal weighting), this score was termed the \"CONSORT score\".\n Urology trials: In total 122 RCT abstracts were identified which met the inclusion criteria for this study. From these, 32 were excluded as they were follow-up studies, involved a virtual procedure or were a cost analysis, leaving 90 RCTs published across 35 different journals which were analysed (68.2%, 90/122). The average score of 11.1 for urological trials indicates that RCTs in our sample do not comply with the CONSORT statement. No trials reported how they implemented their randomisation process. Only 46% of RCTs stated that they had permission from an ethics review board, 20% had declared their sources of funding, 14% stated whether there were any conflicts of interest and only 1.1% stated their trial registry number. For non-urological studies, an average CONSORT score of 11.2 was obtained.\n Clinical research teams conducting RCTs in urology and other surgical disciplines demonstrate poor compliance with the CONSORT statement. We would recommend that trials should be registered at their outset and that urological and other surgical journals to consider supporting the CONSORT statement and to have compliance 'hard-wired' into their submission, editorial and peer-review processes. Since it seems the best researchers are unable to produce an RCT results which enable surgical techniques to be critically assessed, there is a need for education about the CONSORT statement and its importance at all levels of surgical training. We believe that an open debate is needed on the possible role of other research designs, such as tracker studies. Whether this study actually raises the question of how appropriate RCTs are to surgical techniques, we leave to the reader.", "Randomized controlled trials (RCTs) are suitable for meta-analysis and systematic reviews provided they are of high quality and are easy to retrieve. We determined these attributes of RCTs in obstetrical anaesthesia in a sample of available journals that are indexed in MEDLINE.\n Randomized controlled trials published between January 1985 and December 1994 in seven anaesthetic and three obstetric journals were identified by a MEDLINE search, and by handsearch of the same journals. Each RCT was assigned a quality score by a blinded rater using a reliable and validated scaled. The quality of each RCT was described and compared over time and by journal. The comparative yield of MEDLINE and hand-search was evaluated.\n Three hundred and forty RCTs were retrieved by MEDLINE and handsearch. Two hundred and twenty seven (65%) were identified by the MEDLINE search and 333 by the handsearch (98%). The median quality score was 3/5. There was no difference in score over time. Anesthesiology had the highest median score, Anaesthesia had the lowest (P < 0.05).\n Care must be taken when reviewing obstetrical anaesthesia research. Strategies in addition to a MEDLINE search must be used to identify RCTs since more than one third were missed using MEDLINE alone. Poor quality RCTs are more likely to be biased in favour of a new treatment. Therefore, to increase the validity of reviews sensitivity analyses based on quality should be done.", "Randomized controlled trials (RCTs) of interventions provide the highest level of evidence about efficacy but their value either alone or within a meta-analysis is dependent on its methodological quality. For this reason recent RCTs in organ transplantation were assessed for quality. RCTs published between 2004 and 2006 (n = 332) were assessed, after excluding duplicate and nonEnglish reports. Quality was evaluated using the Jadad score plus allocation concealment and intention to treat analysis. We noted journal type, journal author instructions, funding source, sample size and number and location of study centres. Around one-third of RCTs had a Jadad score of 3 or greater (indication of a methodologically good quality trial) and the other two parameters were satisfied in just over one third. Although the majority of trials were published in speciality journals the quality of those published in general journals was superior. Commercially sponsored trials were of better quality as were multicentre trials in contrast to single centre trials. Overall quality of reporting of RCTs in organ transplantation is poor and as RCTs provide the highest level of evidence in evaluations of interventions there needs to be a concerted effort within the transplant community to improve the standards of RCTs.", "As part of the Cochrane Collaboration's international research endeavour, the authors carried out a handsearch of the Journal of the Royal Naval Medical Service from 1948 to 1998, searching for randomised controlled trials (RCTs) and controlled clinical trials (CCTs). Five trials were identified, of which three were RCTs and two were CCTs. The first trial was published in 1960. The identified trials were in the fields of dentistry (two trials), gastroenterology, occupational medicine and orthopaedic surgery. Of the five trials, only two had been located previously through a rigorous interrogation of Medline. The three newly identified trials were reported to the UK Cochrane Centre, and details of these three trials were entered into Medline for use by clinicians and investigators in the future.", "Increased attention has been directed at the quality of randomized controlled trials (RCTs) and how they are being reported. We examined leading anesthesiology journals to identify if there were specific areas for improvement in the design and analysis of published clinical studies. All RCTs that appeared between January 2000 and December 2000 in leading anesthesiology journals (Anesthesiology,Anesthesia & Analgesia,Anaesthesia, and Canadian Journal of Anaesthesia) were retrieved by a MEDLINE search. We used a previously validated assessment tool, including 14 items associated with study quality, to determine a quality score for each article. The overall mean weighted quality score was 44% +/- 16%. Overall average scores were relatively high for appropriate controls (77% +/- 7%) and discussions of side effects (67% +/- 6%). Scores were very low for randomization blinding (5% +/- 2%), blinding observers to results (1% +/- 1%), and post-beta estimates (16% +/- 13%). Important pretreatment clinical predictors were absent in 32% of all studies. Significant improvement in the reporting and conduct of RCTs is required and should focus on randomization methodology, the blinding of investigators, and sample size estimates. Repeat assessments of the literature may improve the adoption of guidelines for the improvement of the quality of randomized controlled trials.", "Several randomised clinical trials (RCTs) of analgesics in postoperative pain after traumatic or orthopaedic surgery (TOS) have been published, but no studies have assessed the quality of these reports. We aimed to examine the quality of reporting RCTs on analgesics for postoperative pain after TOS.\n Reports of RCTs assessing analgesics in postoperative pain after TOS were systematically searched from electronic databases. The quality of reports was assessed using the CONSORT checklist (scoring range from 0 to 22). The quality was considered poor when scoring was 12 or lesser. The publication year and the impact factor of journals were recorded.\n A total of 92 reports of RCTs were identified and 69 (75%) scored 12 or lesser in CONSORT checklist (range 5-17). The mean (SD) CONSORT score of all reports was 10.6 (2.7). Missing CONSORT items included primary and secondary outcome measures (11%), the specific objectives and hypothesis definition (12%), the sample size calculation (12%), the dates defining the periods of recruitment (12%), the discussion of external validity of findings (14%), the allocation sequence generation (24%), and the interpretation of potential bias or imprecision of results (25%). There was a little improvement in CONSORT scores over time (r = 0.62; p < 0.001) and with impact factor of journals (r = 0.30; p < 0.001).\n Quality of reporting RCTs on analgesics after TOS is poor. Reporting of those RCTs should be improved according to methodological standard checklists in the next years.", "To test the hypothesis that surgeon volume would not predict short- and long-term outcomes when evaluated in the setting of technical credentialing.\n Surgical volume is a known predictor of outcomes; the importance of technical credentialing has not been evaluated.\n Fifty-three credentialed surgeons operated on 871 patients in the Clinical Outcomes of Surgical Therapy Study (NCT00002575), investigating laparoscopic versus open surgery for colon cancer. Credentialing required that each surgeon document performance of at least 20 laparoscopic colon cases and demonstrate oncologic techniques on a video-recorded case. Surgeons were separated based on volume entered into the trial (low, < or =5 cases (n = 39); medium, 6-10 cases (n = 9); or high, >10 cases (n = 5)) and compared by outcomes.\n Patients treated by high volume compared with medium or low volume surgeons were older (70, 66, and 68 years; P < 0.001), more often had right-sided tumors (63%, 46%, and 53%; P < 0.001) and had more previous operations (48%, 38% and 45%; P < 0.004), respectively. Mean operative times were shorter (123, 147 and 145 minutes; P < 0.001), distal margins longer (13.4, 12.4 and 11.6 cm; P = 0.005), and lymph node harvest greater (14.8, 12.8, 12.6; P = 0.05) for high versus medium versus low volume surgeons. However, rates of conversion, complications, 5-year survival, and disease-free survival showed no significant differences.\n When tested in a randomized controlled trial with case-specific surgical technical credentialing and auditing, surgeon volume did not predict differences in rates of conversion, complications, or long-term cancer outcomes. Case-specific technical credentialing should be further studied specific to the role it could play in creating consistent, high quality outcomes.", "The effectiveness of interventions for developing critical appraisal skills in practicing physicians has not been studied, despite the documented importance of reading the literature in caring for patients and in continuing professional development. The objective of this study was to evaluate whether an Internet-based intervention would lead to enhanced critical appraisal skills in practicing surgeons.\n General surgeons who agreed to participate were randomized into 2 groups. The intervention was a curriculum in critical appraisal skills that included a clinical and methodologic article, a listserve discussion, and clinical and methodologic critiques. The control group received only the clinical articles. The primary outcome measure was a previously validated 2-hour test of critical appraisal.\n Of the 55 surgeons who completed the examination, subjects in the intervention group performed better on the test of critical appraisal skills than those in the control group (mean score: intervention group, 58% +/- 8 vs control group, 50% +/- 8), with a large effect size of 1.06 standard deviation units (t+3.92, P <.0001). Training conditions accounted for 22% of the variance in total scores.\n A multifaceted, Internet-based intervention resulted in improved critical appraisal skills of practicing general surgeons.", "New Residency Review Committee requirements in general surgery require 50 colonoscopies. Simulators have been widely suggested to help prepare residents for live clinical experience. We assessed a computer-based colonoscopy simulator for effective transfer of skills to live patients.\n A randomized controlled trial included general surgery and internal medicine residents with limited endoscopic experience. Following a pretest, the treatment group (n = 12) practiced on the simulator, while controls (n = 12) received no additional training. Both groups then performed a colonoscopy on a live patient. Technical ability was evaluated by expert endoscopists using previously validated assessment instruments.\n In the live patient setting, the treatment group scored significantly higher global ratings than controls (t(22) = 1.84, P = .04). Only 2 of the 8 computer-based performance metrics correlated significantly with previously validated global ratings of performance.\n Residents trained on a colonoscopy simulator prior to their first patient-based colonoscopy performed significantly better in the clinical setting than controls, demonstrating skill transfer to live patients. The simulator's performance metrics showed limited concurrent validity, suggesting the need for further refinement.", "To describe preliminary work undertaken for development of a nursing contribution to the Cochrane Collaboration. To ascertain whether there are randomised controlled trials (RCTs) on nursing care which need to be identified for inclusion in systematic reviews of the effects of health care.\n Searches by Medline (1966-94) and by hand of 11 nursing research journals from inception to the end of 1994 to identify RCTs and systematic reviews; and a comparison of searches by hand and by Medline for three nursing research journals.\n Total number of RCTs identified and number of RCTs published in nursing journals; the sensitivity of Medline searches; and aspects of nursing care evaluated by RCT.\n The work is ongoing and 522 reports of RCTs and 20 systematic reviews of effectiveness have been identified so far. The sensitivity of Medline searches for RCTs in nursing journals is as low as 36% for one journal and the lack of reference to research design in the title or abstract was the main reason for the lack of sensitivity.\n There are RCTs that evaluate aspects of nursing care, and are published in nursing and non-nursing journals, and are largely undertaken by nurses. These must be reviewed in ongoing systematic reviews of the effects of health care (including those undertaken as part of the Cochrane Collaboration). Nursing journals must be hand searched to identify these studies as the lack of reference to study design in the titles and abstracts of nursing trials leads to poor indexing in electronic databases such as Medline.", "As part of the Cochrane Collaboration's international research endeavour, the authors carried out a handsearch of the RAMC Journal from 1948 to 1998, searching for randomised controlled trials (RCTs) and controlled clinical trials (CCTs). Ten trials were identified, of which 6 were RCTs and 4 were CCTs. The first trial was published in 1967. Four of the 10 identified trials were in the field of respiratory medicine, and 2 were in obstetrics and gynaecology. Of the 10 trials, only 3 had been found through a rigorous interrogation of Medline. The 7 newly identified trials were reported to the UK Cochrane Centre, and summary details of these trials were entered into Medline for use by clinicians and investigators in the future.", "To demonstrate that virtual reality (VR) training transfers technical skills to the operating room (OR) environment.\n The use of VR surgical simulation to train skills and reduce error risk in the OR has never been demonstrated in a prospective, randomized, blinded study.\n Sixteen surgical residents (PGY 1-4) had baseline psychomotor abilities assessed, then were randomized to either VR training (MIST VR simulator diathermy task) until expert criterion levels established by experienced laparoscopists were achieved (n = 8), or control non-VR-trained (n = 8). All subjects performed laparoscopic cholecystectomy with an attending surgeon blinded to training status. Videotapes of gallbladder dissection were reviewed independently by two investigators blinded to subject identity and training, and scored for eight predefined errors for each procedure minute (interrater reliability of error assessment r > 0.80).\n No differences in baseline assessments were found between groups. Gallbladder dissection was 29% faster for VR-trained residents. Non-VR-trained residents were nine times more likely to transiently fail to make progress (P <.007, Mann-Whitney test) and five times more likely to injure the gallbladder or burn nontarget tissue (chi-square = 4.27, P <.04). Mean errors were six times less likely to occur in the VR-trained group (1.19 vs. 7.38 errors per case; P <.008, Mann-Whitney test).\n The use of VR surgical simulation to reach specific target criteria significantly improved the OR performance of residents during laparoscopic cholecystectomy. This validation of transfer of training skills from VR to OR sets the stage for more sophisticated uses of VR in assessment, training, error reduction, and certification of surgeons.", "To evaluate the reporting quality of key methodological items in randomized controlled trials (RCTs) in four general clinical ophthalmology journals.\n The reporting of 11 key methodological items in RCTs published in American Journal of Ophthalmology, Archives of Ophthalmology, British Journal of Ophthalmology and Ophthalmology in the year 2005 was assessed.\n Sixty-seven eligible RCTs were assessed and the mean number of items reported was 6.3 per RCT. No significant difference in the mean number of items reported was found between the four journals (P=0.20). The most frequently reported item was ethics approval and informed consent (97.0%), followed by masking status (85.1%), description of withdrawals (76.1%), adverse events (73.1%), and intention-to-treat analysis (71.6%). Details on sequence generation, randomization restriction, allocation concealment, allocation implementation, patient flow diagrams, and sample size calculation were reported in <50% of the RCTs assessed. Both sample size and page length of the RCTs correlated with the number of methodological items reported (P=0.024 and P=0.008, respectively).\n Similar to other specialties, rooms for improvement exist in the reporting of key methodological items of RCTs in clinical ophthalmic journals. Stricter adoption of the CONSORT statement might enhance the reporting quality of RCTs in ophthalmic journals.", "The \"fulcrum effect\" of the body wall on surgical instrument manipulation is a major hurdle for novice endoscopic surgeons. Virtual reality training has not previously been evaluated as a means to overcome this problem.\n 16 participants with no experience of endoscopy were required to make multiple defined incisions under laparoscopic laboratory conditions within 2-minute periods. Half of the subjects were randomized to receive initial training on the Minimally Invasive Surgical Trainer, Virtual Reality (MIST VR) computer programme.\n Participants with MIST VR training made significantly more correct incisions (P = 0.0001) than the control group on test trial 1, and even after extended practice by both groups (P = 0.0001). They were also significantly more likely to actively use both hands to perform the endoscopic evaluation task (P = 0.01).\n Virtual reality training represents a potential, viable solution for junior endoscopists, for overcoming the \"fulcrum effect\", in a replicable, safe learning environment which allows objective and reliable quantification of skill levels by trainers.", "Adoption of evidence-based practice (EBP) policy has implications for clinicians and researchers alike. In fields that have already adopted EBP, evidence-based practice guidelines derive from systematic reviews of research evidence. Ultimately, such guidelines serve as tools used by practitioners. Systematic reviews of treatment efficacy and effectiveness reserve their strongest endorsements for treatments that are supported by high-quality randomized clinical trials (RCTs). It is unknown how well RCTs reported in behavioral science journals fare compared to quality standards set forth in fields that pioneered the evidence-based movement. We compared analytic quality features of all behavioral health RCTs (n = 73) published in three leading behavioral journals and two leading medical journals between January 2000 and July 2003. A behavioral health trial was operationalized as one employing a behavioral treatment modality to prevent or treat an acute or chronic physical disease or condition. Findings revealed areas of weakness in analytic aspects of the behavioral health RCTs reported in both sets of journals. Weaknesses were more pronounced in behavioral journals. The authors offer recommendations for improving the analytic quality of behavioral health RCTs to ensure that evidence about behavioral treatments is highly weighted in systematic reviews.\n (c) 2006 Wiley Periodicals, Inc.", "Timely adoption of clinical practice guidelines is more likely to happen when the guidelines are used in combination with adjuvant educational strategies that address social as well as rational influences.\n To implement the conservative, evidence-based approach to low-back pain recommended in national guidelines, with the anticipated effect of reducing population-based rates of surgery.\n A randomized, controlled trial.\n Ten communities in western Washington State with annual rates of back surgery above the 1990 national average (158 operations per 100,000 adults).\n Spine surgeons, primary care physicians, patients who were surgical candidates, and hospital administrators.\n The five communities randomized to the intervention group received a package of six educational activities tailored to local needs by community planning groups. Surgeon study groups, primary care continuing medical education conferences, administrative consensus processes, videodisc-aided patient decision making, surgical outcomes management, and generalist academic detailing were serially implemented over a 30-month intervention period.\n Quarterly observations of surgical rates.\n After implementation of the intervention, surgery rates declined in the intervention communities but increased slightly in the control communities. The net effect of the intervention is estimated to be a decline of 20.9 operations per 100,000, a relative reduction of 8.9% (P = 0.01).\n We were able to use scientific evidence to engender voluntary change in back pain practice patterns across entire communities.", "Randomized clinical trials (RCTs) provide the most reliable therapeutic information available. Unfortunately, there are no systemic listing of RCTs. We compared a MEDLARS search of 3686 biomedical journals for RCTs with a manual search of the medical literature for the period 1966-1982. For the former search we used subject headings (1) liver disease or (2) biliary tract disease and subheadings (1) drug therapy, (2) surgery, (3) radiotherapy, or (4) therapy, and check tags (1) comparative study or (2) clinical research. For the manual search, the contents of 34 arbitrarily selected, gastroenterologic, hepatologic, surgical, or general journals were perused. The MEDLARS search identified 160 RCTs and 29 others were found in the references of the 160. One hundred fifty-four RCTs were identified by both methods. The manual search identified 208 RCTs and an additional 34 were found in the references of the 208. The MEDLARS search identified only 107 of 208 RCTs found in the references of the 208. The MEDLARS search identified only 107 of 208 RCTs found manually in the 36 journals, an efficiency rate of 51%. We estimate that 330 hepatobiliary RCTs had been published during this 17-year period. Sixty percent of the RCTs found by MEDLARS used the key word \"randomized,\" \"double blind,\" or \"controlled\" in the title, compared to 36% in those found by the manual search. In order to retrieve RCTs, it is essential that editors require that RCTs be identified in their titles or key words by specific terms such as \"controlled,\" \"randomized,\" and \"double blind,\" that papers be so catalogued and indexed, and that searchers be instructed in appropriate search strategies.", "Cumulative meta-analysis of clinical trials (a Bayesian interpretation for accumulating evidence) will profoundly affect medical care by summarizing evidence in the assessment of technology innovations. Application of the technique to the randomized control trials (RCTs) of streptokinase treatment of acute myocardial infarction, reduction of peri-operative mortality by antibiotic prophylaxis, and prevention of death from bleeding peptic ulcers has revealed efficacy years before it was suspected by any other means. Arrangement of the trials according to event rate in the controls, effect sizes, quality of the trials or according to covariables of interest has supplied unique information. If carried out prospectively the technique supplies invaluable information regarding indications for another trial, the number of patients necessary to determine the validity of past trends, and the type of patients who might be benefitted. Careful examination in a cumulative manner of the prior trials can reduce the need for future large trials.", "Shortened hospitalizations following cardiac surgery necessitate re-evaluation of how pertinent information for self-care management and reduction of coronary artery disease risk factors can be incorporated into an effective inpatient cardiac patient teaching program. This study investigated the effect of three different teaching approaches (i.e., an inpatient teaching program, a postdischarge telephone follow-up program, and a postdischarge group teaching program) among 90 patients who had undergone coronary artery bypass graft surgery. Teaching outcomes were evaluated in this study by use of the Heart Disease Management Questionnaire and Cardiac Surgical Patient Teaching Satisfaction Inventory. Analyses of the data revealed similar patient teaching outcomes regardless of the type of teaching intervention the participant received. Findings supported the effectiveness of the inpatient teaching protocol which focused on \"survival skills\" for self-care management postdischarge. The findings are important in the redesign of teaching programs which are efficient yet meaningful to the patient within today's health care environment. Additional findings indicated that patients who had longer lengths of stay and those with more vessels bypassed were the least satisfied with their teaching. Further implications for nurses involved in patient teaching are discussed.", "Laparoscopic surgery requires a different set of skills than traditional open surgery. The acquisition of basic laparoscopic skills may help novices when learning laparoscopic procedures. This study tested the hypothesis that the combination of virtual reality and box trainers leads to better basic laparoscopic skill acquisition than either method alone or no training.\n A randomized control trial involving preclinical medical students with no prior operative experience was performed. The students were grouped according to four training methods: virtual reality training, inanimate box training, a combination of both, and no training (control). The pre- and posttraining scores for four skills in the porcine laboratory were the metrics chosen for this study.\n A total of 65 students participated in this study. There were no differences among any of the pretraining scores (p > 0.05). The posttraining times differed between the four groups. Post hoc analyses showed statistically significant differences (p < 0.05) between the participants trained with both trainers and the control subjects.\n Our data demonstrate that the combination of virtual reality training and inanimate box training leads to better laparoscopic skill acquisition than either training method alone or no training at all. Optimal preclinical laparoscopic training should incorporate both virtual reality trainers and inanimate box trainers.", "There is an increasing drive to make nursing care evidence-based. High quality evidence from systematic reviews relevant to postoperative pain relief exists, yet pain after surgery remains poorly controlled for many patients. This study aimed to assess whether implementing evidence-based pain management improved postoperative pain outcomes. Pain on a 0-10 scale was the primary outcome and analgesic consumption a secondary outcome. A baseline audit was undertaken on four surgical wards to establish whether there was a need for the study. A randomized-controlled trial was then designed to assess the effects of implementing an evidence-based approach to postoperative pain management. The four wards were randomized to receive the intervention or act as a control. Outcomes were assessed 3 months after the intervention on both intervention and control wards. The intervention (implementation of an oral analgesic algorithm derived from systematic reviews) was then implemented on the control wards and outcomes reassessed after 3 months on the control wards. The intervention was designed using an evidence-based approach to effective implementation. Four interactive sessions covered: (1) detailed feedback of baseline data and discussion (utilizing audit and feedback), (2) why systematic reviews, analgesic league tables and choice of drugs to develop an analgesic algorithm (see Figure 1), (3) principles of evidence based health care (EBHC), including critical appraisal and (4) facilitation and change workshop. The findings revealed no significant differences in pain level or drug use between the intervention and control wards. However, the control wards also changed during the control period. Possible explanations for this are discussed. When looking at changes compared with baseline, both intervention and control wards increased their use of algorithm drugs and reduced use of non-algorithm drugs during the study. No effects were found on pain in the intervention wards. Pain ratings at rest since surgery, on movement since surgery and worst pain on movement were significantly reduced compared with baseline in the control wards. Although there are many pressures to utilize a randomized-controlled trial study design in the culture of evidence-based health care, there will be times, especially when implementing complex changes in practice that other types of design should be considered.", "A prospective randomized controlled trial (RCT) of multimodal perioperative management protocol in patients undergoing elective colorectal resection for cancer.\n This study evaluates the use of a multimodal package in colorectal cancer surgery in the context of an RCT.\n Patients for elective resection for colorectal cancer were offered trial entry. Participants were stratified by sex and requirement for a total mesorectal excision and centrally randomized. Multimodal patients received intravenous fluid restriction, unrestricted oral intake with prokinetic agents, early ambulation, and fixed regimen epidural analgesia. Control patients received intravenous fluids to prevent oliguria, restricted oral intake until return of bowel motility, and weaning regimen epidural analgesia. Adherence to both regimens was reinforced using a daily checklist and protocol guidance sheets. Discharge decision was made using pre-agreed criteria. The primary endpoint was postoperative stay, and achievement of independence milestones. Secondary endpoints were postoperative complications, readmission rates, and mortality. Analysis was by intention to treat.\n Seventy patients were recruited. Approximately one fourth underwent TME. Median ages were similar (69.3 vs. 73.0 years). The median stay was significantly reduced in the multimodal group (5 vs. 7 days; P < 0.001, Mann-Whitney U test). Patients in the control arm were 2.5 times as likely to require a postoperative stay of more than 5 days. Patients in the multimodal group had less cardiorespiratory and anastomotic complications but more readmissions. There were 2 deaths, both controls.\n This RCT provides level 1b evidence that a multimodal management protocol can significantly reduce postoperative stay following colorectal cancer surgery. Morbidity and mortality are not increased." ]	Limited evidence is now available to support some aspects of surgical practice. Surgeons should be encouraged to perform further RCTs in this field.
CD009219	[ "19813275", "17710657", "12789464" ]	[ "Amifostine does not prevent platinum-induced hearing loss associated with the treatment of children with hepatoblastoma: a report of the Intergroup Hepatoblastoma Study P9645 as a part of the Children's Oncology Group.", "Toxicity prevention with amifostine in pediatric osteosarcoma patients treated with cisplatin and doxorubicin.", "Randomized phase III trial of postoperative radiochemotherapy +/- amifostine in head and neck cancer. Is there evidence for radioprotection?" ]	[ "The current study was conducted to determine whether amifostine is effective in reducing the toxicities associated with the administration of platinum-containing regimens in children with hepatoblastoma (HB).\n Patients were enrolled on P9645 beginning in March of 1999. Patients who had stage I/II disease received treatment with 4 cycles of combined cisplatin, 5-fluorouracil, and vincristine (C5V) with or without amifostine. Patients who had stage III/IV disease were randomized to receive treatment with 6 cycles of either C5V with or without amifostine or carboplatin alternating with cisplatin (CC) with or without amifostine. Patients who were randomized to receive amifostine were given a dose of 740 mg/m2 intravenously over 15 minutes before each administration of a platinum agent.\n Eighty-two patients were considered in a special interim analysis of the incidence of toxicity. The disease outcome for patients who received amifostine was similar to the outcome for patients who did not receive amifostine (P=.22). The incidence of significant hearing loss (>40 dB) was similar for patients who did or did not receive amifostine (38% [14 of 37 patients] vs 38% [17 of 45 patients], respectively; P=.68). There were no differences in the incidence of renal or bone marrow toxicities evaluated. Patients who received amifostine had a higher incidence of hypocalcemia (5% vs 0.5%; P=.00006).\n Amifostine in the doses and schedule used in this study failed to significantly reduce the incidence of platinum-induced toxicities in patients with HB.\n Copyright (c) 2009 American Cancer Society.", "Amifostine has emerged as a pancytoprotectant shown protection against nephrotoxicity, neurotoxicity and ototoxicity in preclinical studies.\n We designed a prospective comparative randomized trial to evaluate the cytoprotective effects of amifostine in patients with osteosarcoma receiving cisplatin and doxorrubicin. Patients were evaluated for renal, hearing and cardiac toxicity.\n We included 28 patients, mean age was 11.6 years, five had metastatic disease. Fifteen patients received amifostine and 13 did not. 20% of patients receiving amifostine developed renal toxicity compared to 30% in the control group (p = 0.318). Grade 1 and 2 audiologic toxicity was present in 100% of the experimental group against 85% of the controls (p = 0.501). Grade 1 cardiac toxicity was present in 2 patients in the control group (p = 0.175). There were no statistical significant differences between the two groups for chemotherapy-related toxicity. Response to chemotherapy was significantly better in the amifostine group.\n amifostine did not reduce the ototoxicity and nephrotoxicity of our treatment regime. It was not well tolerated due to emesis. It is a selective cytoprotectant without reducing the effect of chemotherapy.", "Experimental and clinical data suggest a reduction of radiation-induced acute toxicity by amifostine (A). We investigated this issue in a randomized trial comparing radiochemotherapy (RT + CT) versus radiochemotherapy plus amifostine (RC + CT + A) in patients with head and neck cancer.\n 56 patients with oro-/hypopharynx or larynx cancer (T1-2 N1-2 G3, T3-4 N0-2 G1-3) were randomized to receive RC + CT alone or RC + CT + A. Patients were irradiated up to 60 Gy (R0) or 70 Gy (R1/2) and received chemotherapy (70 mg/m(2) carboplatin, day 1-5 in week 1 and 5 of radiotherapy). 250 mg amifostine were applied daily before each radiotherapy session. Acute toxicity was evaluated according to the Common Toxicity Criteria (CTC). As for acute xerostomia, patients with laryngeal cancer were excluded from evaluation.\n 50 patients were evaluable (25 patients in the RC + CT, 25 patients in the RC + CT + A group). Clinical characteristics were well balanced in both treatment groups. Amifostine provided reduction in acute xerostomia and mucositis but had no obvious influence on Karnofsky performance status, body weight, cutaneous side effects, and alopecia. The differences between both groups were statistically significant for acute xerostomia and nonsignificant, but with a trend for mucositis.\n According to our results, there is a radioprotective effect on salivary glands and a potential effect on oral mucosa by amifostine in postoperative radiotherapy combined with carboplatin. To improve the radio- and chemoprotective effects of amifostine in clinical practice, the application of a higher dose (> 250 mg) seems to be necessary." ]	At the moment there is no evidence from individual studies in children with osteosarcoma and hepatoblastoma treated with different platinum analogues and dosage schedules which underscores the use of amifostine as an otoprotective intervention as compared to no additional treatment. Since pooling of results was not possible and all studies had serious methodological limitations, no definitive conclusions can be made. It should be noted that 'no evidence of effect', as identified in this review, is not the same as 'evidence of no effect'. Based on the currently available evidence, we are not able to give recommendations for clinical practice. For other possible otoprotective medical interventions and other types of malignancies no eligible studies were identified, so no conclusions can be made about their efficacy in preventing ototoxicity in children treated with platinum-based therapy. More high quality research is needed.
CD003690	[ "19455296", "2689036", "9879787", "14606735", "18505948" ]	[ "[Interpersonal psychotherapy and pharmacotherapy for post-stroke depression. Feasibility and effectiveness].", "[Treatment of pathological laughing with amitriptyline].", "Fluoxetine as a treatment for post-stroke emotionalism.", "A randomized controlled trial of an education and counselling intervention for families after stroke.", "Escitalopram and problem-solving therapy for prevention of poststroke depression: a randomized controlled trial." ]	[ "Only few studies investigated the effectiveness of psychotherapy in post-stroke depression (PSD). The aim of this feasibility study was to compare interpersonal psychotherapy, pharmacotherapy, and their combination regarding depression and rehabilitation outcome.\n Post-stroke depression was found in 35% of 485 stroke patients examined. Seventy-four PSD patients were randomised to one of three treatment conditions. Severity of depression was measured by the Hamilton Depression Rating Scale and the Hospital Anxiety and Depression Scale. The Barthel Index and a questionnaire for health-related quality of life were used as measurements of rehabilitation outcome.\n There were no significant differences between the three groups in patient mood or rehabilitation outcome. Concerning the severity of depression, quality of life, and social support, all patients showed benefits from antidepressive treatment. In addition a correlation was found between rehabilitation outcome and depression.\n In this feasibility study all antidepressive treatments were successfully implemented in the rehabilitation of post-stroke depressed patients. Combination therapy (interpersonal psychotherapy plus medication) was as effective as one of those elements alone. Because of the small sample size however, further randomized trials are required.", "We investigated the efficacy of amitriptyline in seven patients with pathological laughing caused by cerebrovascular diseases. In a double-blind placebo-controlled cross-over trial comparing amitriptyline with placebo, 5 of these 7 patients were judged to have shown improvement with amitriptyline, and 1 patient improved with placebo. This difference was statistically significant. No significant side effect of amitriptyline was observed. There was no significant change between amitriptyline and placebo in both self-rating depression scale and minimental state test score. These results suggested that amitriptyline was useful in treating pathological laughing.", "The effectiveness of fluoxetine compared to placebo in the treatment of post-stroke emotionalism was investigated in 20 patients using a double-blind protocol. A total of 19 patients completed the study, as one subject in the treatment group had to be withdrawn. The subjects receiving fluoxetine showed a statistically and clinically significant improvement in their emotionalism compared to the placebo group, which was apparent in the majority of subjects from the third day of treatment.", "To determine whether education and counselling after stroke leads to improved family functioning and psychosocial outcomes for stroke patients and their spouses, and better functional and social outcomes for patients.\n Two-group randomized controlled trial. Data were collected on admission to and discharge from rehabilitation, and again six months later.\n Rehabilitation units at Repatriation General Hospital and Griffith Hospital, in Adelaide, South Australia.\n Sixty-two stroke patients and their spouses, 32 in the intervention group and 30 in the control group.\n Stroke information package and three visits from a social worker trained in family counselling.\n Family functioning: McMaster Family Assessment Device (FAD); functional status: Barthel Index (BI); social recovery: Adelaide Activities Profile (AAP); depression: Geriatric Depression Scale (GDS); anxiety: Hospital Anxiety and Depression Scale (HADS); mastery: Mastery Scale (MS); health status: SF-36.\n At six months the intervention group had better family functioning for both patients (mean FAD difference 0.19) and spouses (mean difference 0.09). A modest benefit in functional status for intervention patients (mean BI difference 1.3) was related to improved family functioning. Intervention patients reported better social recovery (mean AAP differences: domestic chores 5.7, household maintenance 4.6, social activities 11.5), but there were no significant effects on depression, anxiety, mastery or health status.\n An education and counselling intervention maintained family functioning, and in turn led to improved functional and social patient outcomes. This approach helps patients and their spouses to make the optimal adjustment to living with stroke.", "Depression occurs in more than half of patients who have experienced a stroke. Poststroke depression has been shown in numerous studies to be associated with both impaired recovery in activities of daily living and increased mortality. Prevention of depression thus represents a potentially important goal.\n To determine whether treatment with escitalopram or problem-solving therapy over the first year following acute stroke will decrease the number of depression cases that develop compared with placebo medication.\n A multisite randomized controlled trial for prevention of depression among 176 nondepressed patients was conducted within 3 months following acute stroke from July 9, 2003, to October 1, 2007. The 12-month trial included 3 groups: a double-blind placebo-controlled comparison of escitalopram (n = 59) with placebo (n = 58), and a nonblinded problem-solving therapy group (n = 59).\n The main outcome measure was the development of major or minor poststroke depression based on symptoms elicited by the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) and the diagnostic criteria from DSM-IV for depression due to stroke with major depressive-like episode or minor depression (ie, research criteria).\n Patients who received placebo were significantly more likely to develop depression than individuals who received escitalopram (11 major and 2 minor cases of depression [22.4%] vs 3 major and 2 minor cases of depression [8.5%], adjusted hazard ratio [HR], 4.5; 95% confidence interval [CI], 2.4-8.2; P < .001) and also more likely than individuals who received problem-solving therapy (5 major and 2 minor cases of depression [11.9%], adjusted HR, 2.2; 95% CI, 1.4-3.5; P < .001). These results were adjusted for history of mood disorders and remained significant after considering possible confounders such as age, sex, treatment site, and severity of impairment in the model. Using an intention-to-treat conservative method of analyzing the data, which assumed that all 27 patients who did not start randomized treatment would have developed depression, and controlling for prior history of mood disorders, escitalopram was superior to placebo (23.1% vs 34.5%; adjusted HR, 2.2; 95% CI, 1.2-3.9; P = .007), while problem-solving therapy was not significantly better than placebo (30.5% vs 34.5%; adjusted HR, 1.1; 95% CI, 0.8-1.5; P = .51). Adverse events, including all-cause hospitalizations, nausea, and adverse effects associated with escitalopram were not significantly different between the 3 groups.\n In this study of nondepressed patients with recent stroke, the use of escitalopram or problem-solving therapy resulted in a significantly lower incidence of depression over 12 months of treatment compared with placebo, but problem-solving therapy did not achieve significant results over placebo using the intention-to-treat conservative method of analysis.\n clinicaltrials.gov Identifier: NCT00071643." ]	Antidepressants can reduce the frequency and severity of crying or laughing episodes. The effect does not seem specific to one drug or class of drugs. Our conclusions must be qualified by several methodological deficiencies in the studies. More reliable data are required before recommendations can be made about the treatment of post-stroke emotionalism.
CD006199	[ "10775784", "11920300", "15526058", "10462251" ]	[ "Safety and immunogenicity of a three-component blood-stage malaria vaccine in adults living in an endemic area of Papua New Guinea.", "A recombinant blood-stage malaria vaccine reduces Plasmodium falciparum density and exerts selective pressure on parasite populations in a phase 1-2b trial in Papua New Guinea.", "A randomised, double-blind, controlled vaccine efficacy trial of DNA/MVA ME-TRAP against malaria infection in Gambian adults.", "Human phase I vaccine trials of 3 recombinant asexual stage malaria antigens with Montanide ISA720 adjuvant." ]	[ "A Phase I safety and immunogenicity study with a three-component blood-stage malaria vaccine was conducted in adult male subjects living in an endemic area of Papua New Guinea. The preparations were recombinant proteins which corresponded to parts of the two merozoite surface proteins of Plasmodium falciparum (MSP1 and 2), and of the ring-infected erythrocyte surface antigen (RESA). The three proteins were emulsified with the adjuvant Montanide ISA720. Ten subjects were injected twice (four weeks apart) with the vaccine formulation and two with the adjuvant alone. Mild pain at the site of injection was reported by about half of the subjects but no systemic reaction related to the formulation occurred. There was a sharp rise in geometric mean stimulation index after the second dose compared to baseline for MSP1 and RESA, while the rise was small for MSP2. Geometric mean antibody titres increased for MSP1 during the study, whereas they hardly changed for MSP2 and RESA. The vaccine formulation was safe when used in an already immune population. The vaccine induced good cellular responses, especially for MSP1 and RESA. Boosting of humoral responses was weak, probably because of high baseline antibody levels.", "The malaria vaccine Combination B comprises recombinant Plasmodium falciparum ring-infected erythrocyte surface antigen and 2 merozoite surface proteins (MSP1 and MSP2) formulated in oil-based adjuvant. A phase 1-2b double-blind, randomized, placebo-controlled trial in 120 children (5-9 years old) in Papua New Guinea demonstrated a 62% (95% confidence limits: 13%, 84%) reduction in parasite density in children not pretreated with sulfadoxine-pyrimethamine. Vaccinees had a lower prevalence of parasites carrying the MSP2-3D7 allelic form (corresponding to that in the vaccine) and a higher incidence of morbid episodes associated with FC27-type parasites. These results demonstrate functional activity of Combination B against P. falciparum in individuals with previous malaria exposure. The specific effects on parasites with particular msp2 genotypes suggest that the MSP2 component, at least in part, accounted for the activity. The vaccine-induced selection pressure exerted on the parasites and its consequences for morbidity strongly argue for developing vaccines comprising conserved antigens and/or multiple components covering all important allelic types.", "Many malaria vaccines are currently in development, although very few have been evaluated for efficacy in the field. Plasmodium falciparum multiple epitope (ME)- thrombospondin-related adhesion protein (TRAP) candidate vaccines are designed to potently induce effector T cells and so are a departure from earlier malaria vaccines evaluated in the field in terms of their mechanism of action. ME-TRAP vaccines encode a polyepitope string and the TRAP sporozoite antigen. Two vaccine vectors encoding ME-TRAP, plasmid DNA and modified vaccinia virus Ankara (MVA), when used sequentially in a prime-boost immunisation regime, induce high frequencies of effector T cells and partial protection, manifest as delay in time to parasitaemia, in a clinical challenge model.\n A total of 372 Gambian men aged 15-45 y were randomised to receive either DNA ME-TRAP followed by MVA ME-TRAP or rabies vaccine (control). Of these men, 296 received three doses of vaccine timed to coincide with the beginning of the transmission season (141 in the DNA/MVA group and 155 in the rabies group) and were followed up. Volunteers were given sulphadoxine/pyrimethamine 2 wk before the final vaccination. Blood smears were collected weekly for 11 wk and whenever a volunteer developed symptoms compatible with malaria during the transmission season. The primary endpoint was time to first infection with asexual P. falciparum. Analysis was per protocol. DNA ME-TRAP and MVA ME-TRAP were safe and well-tolerated. Effector T cell responses to a non-vaccine strain of TRAP were 50-fold higher postvaccination in the malaria vaccine group than in the rabies vaccine group. Vaccine efficacy, adjusted for confounding factors, was 10.3% (95% confidence interval, -22% to +34%; p = 0.49). Incidence of malaria infection decreased with increasing age and was associated with ethnicity.\n DNA/MVA heterologous prime-boost vaccination is safe and highly immunogenic for effector T cell induction in a malaria-endemic area. But despite having produced a substantial reduction in liver-stage parasites in challenge studies of non-immune volunteers, this first generation T cell-inducing vaccine was ineffective at reducing the natural infection rate in semi-immune African adults.", "Two phase I vaccine trials were conducted to test the immunogenicity and safety of a vaccine containing three recombinant malaria antigens from the asexual stage of Plasmodium falciparum. The three antigens are a fragment of MSP1 (190LCS.T3); MSP2 and a portion of RESA and were formulated in Montanide ISA720 adjuvant. These trials investigated the dose response of each antigen for eliciting both antibody and T-cell responses and the immunogenicity of a mixture of the antigens compared with the antigens injected separately. All three antigens elicited both antibody and T-cell responses. Strong T-cell responses were observed with 190LCS.T3 and RESA with stimulation indices exceeding 100 for peripheral blood leucocytes in some individuals. The antibody responses were generally weak. The human antibody responses observed with MSP2 in Montanide ISA720 were not significantly different from those obtained in an earlier trial which used MSP2 with alum as the adjuvant. No antigenic competition was observed: volunteers receiving a mixture of antigens had similar responses to those receiving the three antigens at separate sites. Tenderness and pain at the injection site were common over the first few days following immunization. In some volunteers, especially those receiving the highest doses tested, there was a delayed reaction at the injection site with pain and swelling occurring approximately 10 days after injection." ]	The MSP/RESA (Combination B) vaccine shows promise as a way to reduce the severity of malaria episodes, but the effect of the vaccine is MSP2 variant-specific. Pretreatment for malaria during a vaccine trial makes the results difficult to interpret, particularly with the relatively small sample sizes of early trials. The results show that blood-stage vaccines may play a role and merit further development.
CD002916	[ "9489119", "9266880", "11029359", "10894097", "8957368", "9387969", "8398325", "6190551", "7692617", "9692129", "2481558", "9221383", "3536525", "1710483", "7972977", "9596311", "2443762", "9872815", "8952557", "6336983", "20483861", "1720370", "8553306", "8697829", "11697833" ]	[ "A prospective, randomised study comparing the efficacy of talc slurry and bleomycin in the treatment of malignant pleural effusions.", "Prospective randomized trial of talc slurry vs bleomycin in pleurodesis for symptomatic malignant pleural effusions.", "Prospective randomized comparison of thoracoscopic talc poudrage under local anesthesia versus bleomycin instillation for pleurodesis in malignant pleural effusions.", "A comparative study of pleurodesis using talc slurry and bleomycin in the management of malignant pleural effusions.", "Thoracoscopic talc insufflation versus talc slurry for symptomatic malignant pleural effusion.", "Pleurodesis in malignant pleural effusions: a randomized study of tetracycline versus bleomycin.", "A randomised prospective trial of surgical against medical tetracycline pleurodesis in the management of malignant pleural effusions secondary to breast cancer.", "Control of pleural effusions in patients with breast cancer. A randomized trial.", "Chemical pleurodesis in malignant pleural effusions: a randomised prospective study of mepacrine versus bleomycin.", "Treatment of malignant pleural effusion: pleurodesis using a small percutaneous catheter. A prospective randomized study.", "Comparison of intracavitary bleomycin and talc for control of pleural effusions secondary to carcinoma of the breast.", "[Pleurodesis in malignant pleural effusion: bleomycin vs. mitoxantrone].", "A comparison of intracavitary talc and tetracycline for the control of pleural effusions secondary to breast cancer.", "Intrapleural palliative treatment of malignant pleural effusions with mitoxantrone versus placebo (pleural tube alone).", "Tetracycline compared with mechlorethamine in the treatment of malignant pleural effusions. A randomized trial.", "Sclerotherapy for malignant pleural effusions: a prospective randomized trial of bleomycin vs doxycycline with small-bore catheter drainage.", "Intracavitary bleomycin and tetracycline in the management of malignant pleural effusions: a randomized study.", "Intrapleural urokinase versus normal saline in the treatment of complicated parapneumonic effusions and empyema. A randomized, double-blind study.", "Treatment of malignant pleural effusions with a combination of bleomycin and tetracycline. A comparison of bleomycin or tetracycline alone versus a combination of bleomycin and tetracycline.", "Intrapleural tetracycline in malignant pleural effusions. A randomized study.", "Sclerotherapy of telangiectases and reticular veins: a double-blind, randomized, comparative clinical trial of polidocanol, sodium tetradecyl sulphate and isotonic saline (EASI study).", "Intrapleural therapy for malignant pleural effusions. A randomized comparison of bleomycin and tetracycline.", "Randomised trial of corticosteroids in the treatment of tuberculous pleurisy.", "Corticosteroids in the treatment of tuberculous pleurisy. A double-blind, placebo-controlled, randomized study.", "Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: a randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG)." ]	[ "In comparative studies with other agents, insufflated talc has been shown to be the most effective agent in achieving chemical pleurodesis in patients with malignant pleural effusions. The objective of this study is to compare the efficacy of talc administered as slurry (5 g in 50 mL saline) via tube thoracostomy with that of bleomycin (1 mg/kg in 50 mL saline) (which is the most effective agent other than talc). In a randomised, prospective comparative study, twenty-six consecutive patients with proven malignant pleural effusions (recurrent after at least two pleuroscenteses) in whom no pleurodesis attempt had yet been made, and who were symptomatic, had a Karnovski index < or = 50, and an expected survival of one year or less, were included. Therapeutic failure was defined as recurrent pleural fluid > or = 50% of initial volume or requiring pleurocentesis. Recurrence rates (25% vs 21.4%, NS), fever (25% vs 35.7%, NS), pain (0% both groups) and survival (3.75 +/- 3 vs 5.82 +/- 7.15 months, NS) did not differ between bleomycin or talc treated patients. There were no major complications (e.g., empyema) or side-effects. In conclusion, talc slurry and bleomycin are equally effective in achieving chemical pleurodesis via thoracostomy in patients with malignant pleural effusions, and the safety profile of both agents is similar. Since talc is substantially less expensive than bleomycin, talc slurry probably represents the agent of choice for chemical tube thoracostomy pleurodesis.", "Symptomatic malignant pleural effusions are common sequelae in patients with certain malignancies. Pleurodesis via bedside thoracostomy is the current treatment option most commonly used. To our knowledge, this is the first prospective randomized trial to examine which agent, bleomycin or talc slurry, is superior in terms of effectiveness, safety, and cost.\n Between July 1992 and March 1995, 35 patients presenting to our medical center with symptomatic malignant pleural effusions were prospectively randomized to undergo chemical pleurodesis with either bleomycin or talc slurry via bedside thoracostomy. The conditions of patients were assessed and graded before and after treatment concerning pain, dyspnea, and chest radiographs.\n Twenty-nine patients who underwent 33 treatments (14 with bleomycin and 19 with talc) were available for follow-up. Follow-up ranged from 2 weeks to 8 months (mean, 1.7 months). Both groups demonstrated notable improvement in both pain and dyspnea following treatment, but there were no statistically significant differences between groups in the amount of improvement (two-tailed Student's t test). Permanent control of effusions, defined objectively on chest radiograph, was achieved with 11 bleomycin treatments (79%) and 17 talc treatments (90%) (p=0.388). The procedures were well tolerated and no significant adverse effects were observed. Talc is a much less costly agent than bleomycin ($12.36 cost to our medical center per treatment for talc vs $955.83 for bleomycin).\n Given the similar efficacy and significant cost advantage, we conclude that talc is the agent of choice when utilizing pleurodesis for control of symptomatic malignant pleural effusions.", "Induction of pleurodesis offers benefit for patients with metastatic tumors and symptomatic malignant pleural effusions, but the best method for achieving this is still unknown. In this prospective, randomized comparison of two well-established pleurodesis procedures, 36 patients with malignant pleural effusions, expanded lungs after drainage, and expected survival of > 1 mo received either bleomycin instillation (60E) via a small-bore thoracostomy tube or thoracoscopic talc poudrage (5 g) under local anesthesia. Efficacy, safety, and cost could be evaluated for 32 treatments (17 bleomycin, 15 talc) in 31 patients. Recurrence rates of effusion with bleomycin and talc poudrage after 30 d were 41% and 13% (p = 0.12), respectively, those after 90 d were 59% and 13%, respectively (p = 0.01), and those after 180 d were 65% and 13% (p = 0.005), respectively. Neither procedure showed any major adverse effect, and both were equally well tolerated. Cost estimation favored thoracoscopic talc poudrage, both for the initial hospitalization and with regard to recurrences. In conclusion, thoracoscopic talc pleurodesis under local anesthesia is superior to bleomycin instillation for pleurodesis in cases of malignant pleural effusion.", "Differing success rates of various pleurodesis agents have been reported in the management of malignant pleural effusions. A randomized clinical trial was conducted to compare the efficacy of two commonly used agents, talc and bleomycin, for the pleurodesis of malignant pleural effusions.\n Inclusion in the study required proof of a malignant pleural effusion by fluid cytology or pleural biopsy. Exclusion criteria included trapped lung, loculated effusions, recurrent effusions and life expectancy < 1 month. Five grams of talc or 1 unit per kilogram bodyweight of bleomycin mixed in 150 mL of normal saline was administered via tube thoracostomy after complete drainage of the pleural effusion in each patient. Treatment success was defined as the absence of recurrent pleural effusion on the chest radiograph 1 month after pleurodesis.\n Treatment success was achieved in 16 out of 18 patients (89%) in the talc slurry group versus 14 out of 20 patients (70%) in the bleomycin group (P=0.168). Fever and pain were the only side-effects of pleurodesis in both groups.\n These results indicate that talc slurry is as effective as bleomycin in preventing early recurrence of malignant pleural effusions. Pleurodesis with talc instead of bleomycin can result in significant cost savings.", "Talc has been generally accepted to be the most effective sclerosant for chemical pleurodesis, although the optimal route of administration remains unclear.\n We designed a prospective, randomized study to compare video-assisted thoracoscopic talc insufflation with bedside talc slurry in the treatment of malignant pleural effusion. From September 1993 to November 1995, 57 patients were recruited and randomized to either video-assisted thoracoscopic talc insufflation under general anesthesia (n = 28) or talc slurry by the bedside (n = 29). Patients with poor general condition (Karnofsky score less than 30%), poor pulmonary function (forced expiratory volume in 1 second less than 0.5 L), or trapped lungs were excluded from this study. Five grams of purified talc was used for either video-assisted thoracoscopic talc insufflation or talc slurry.\n There was no statistically significant difference between the two groups of patients with respect to age, sex ratio, chest drainage duration, postprocedural hospital stay, parenteral narcotics requirement, complications, or procedure failure (ie, recurrence).\n Video-assisted thoracoscopic talc insufflation has not been shown to be a superior approach compared with talc slurry in our study. Because the former demands more resources, we advocate that talc slurry should be considered as the procedure of choice in the treatment of symptomatic malignant pleural effusion in patients who do not have trapped lungs.", "Malignant pleural effusions are commonly managed with tube thoracostomy drainage followed by chemical pleurodesis. Both tetracycline and bleomycin have been shown to be effective for intrapleural instillation, although neither agent has definitively proved advantages over the other. The aim of the present study was to compare these two agents in terms of response rate and toxicity profile. A prospective, randomized trial was carried out in a single centre. Between May 1993 and January 1996, 62 evaluable patients with proved malignant pleural effusion were allocated to receive either intrapleural tetracycline (1.5 g) or bleomycin (60 mg) after the same drainage procedure. Demographic, clinical and fluid parameter data were comparable in both groups. Response was evaluated at 1, 3 and 6 months after pleurodesis. Mean survival and time to relapse did not differ between the two groups. No statistically significant differences were found in terms of efficacy at each evaluation time. Overall, 16 (52%) and 20 (64%) patients had a recurrence of pleural effusion during follow-up in the tetracycline and bleomycin arms, respectively. Fever was most common in bleomycin-treated patients (p=0.024) while pain was most frequent in the tetracycline arm (nonsignificant). Since no study agent was superior to the other in this trial, we suggest that economic costs, drug availability and medical skill should be considered in the choice of a sclerosing agent.", "Malignant pleural effusion is a frequent complication of metastatic breast cancer leading to a significant degree of morbidity. Drainage of the effusion by thoracocentesis and pleurodesis with tetracycline as the sclerosing agent is an established means of symptomatic relief in these patients. To determine whether the efficacy of tetracycline pleurodesis is improved by surgical rather than medical drainage and instillation of sclerosant, 34 patients were prospectively randomised to a trial comparing the two treatment modalities, of whom 29 were evaluable for response. The total failure rate of primary pleurodesis was 13.4%, the rate of recurrence of effusion within the first month was 24%, and only 1 patient (3.4%) required repeat aspiration in that time period. There was no significant difference in the rate of recurrence or reaspiration of effusion between the two treatment groups. Although the overall survival time from treatment of effusion is significantly longer in the surgical treatment group than in the medical treatment group (P = 0.03), this is likely to be due to factors other than the method of treating the effusion. We conclude that surgical tetracycline pleurodesis has no advantage over medical tetracycline pleurodesis.", "In a controlled randomized trial, 46 patients with pleural effusions secondary to breast cancer were treated at first diagnosis with either intracavitary mustine or talc, to determine which agent produced the more effective pleurodesis. Of the 37 evaluable patients, control of the effusion was achieved in 9/17 (56%) of those treated with mustine and 18/20 (90%) of the talc group (P less than 0.025). This suggests that early treatment with intracavitary talc can effectively palliate this complication of breast cancer.", "The treatment of recurrent pleural effusion in advanced malignant disease should be efficient and with tolerable side effects. Since 1983 intrathoracic instillation of the anti-malaria drug mepacrine has been used to achieve pleurodesis. The cytotoxic drug bleomycin has been claimed to be equally effective and with fewer side effects. The present study was designed to compare these two agents.\n Forty patients with carcinoma and pleural effusions refractory to repeated pleural aspirations over the previous 12 weeks were randomised to receive treatment with intrathoracic instillation of mepacrine or bleomycin. Fluid volumes before and after pleurodesis, drainage time, and side effects were registered and analysed, and the response to treatment was evaluated by clinical examination and chest radiography.\n The amount of fluid produced after treatment in the patients receiving mepacrine was lower than in those receiving bleomycin, and the duration of chest drainage was shorter. After 30 days 16 of 20 in the mepacrine group responded to treatment and 10 of 20 in the bleomycin group. Most patients died during the three months observation period. Moderate side effects occurred equally in both groups.\n Chemical pleurodesis can reduce or stop pleural effusion in many patients, and in this study mepacrine appeared to be more efficient than bleomycin. A prospective study with a larger number of patients is now warranted.", "The aim of this prospective, randomized study was to investigate the possibility of performing pleurodesis using a small percutaneous catheter (Cystofix catheter, CH10, 65 cm) inserted at bedside in patients with recurrent malignant pleural effusion and to compare this catheter with a conventional large bore chest tube (CH24) placed in connection with diagnostic thoracoscopy. After drainage pleurodesis was performed with tetracycline as sclerosing agent. Of 18 evaluable consecutive patients (mean age 67.8 years) nine were randomized for pleurodesis with the small and nine for the large catheter. In the former group, the majority (seven of nine) did not find insertion of the catheter more unpleasant than thoracentesis. In the latter group only a few (two of nine) found insertion comparable with thoracentesis (P < 0.05). All patients found the presence of the large catheter very or somewhat unpleasant (two and seven patients), whereas this was only the case for a few (no and two patients) treated with the small catheter (P < 0.05). In the former group three patients required new thoracentesis, whereas this was only the case for two patients in the latter group (P > 0.05). No complications were seen. We conclude that pleurodesis in patients with recurrent malignant pleural effusion can be performed with a small percutaneous catheter (Cystofix) with an effect similar to that obtained with a large-bore chest tube and with less discomfort for the patient.", "In a prospective randomized study, patients with pleural effusions secondary to breast carcinoma were randomly allocated to be treated by pleurodesis using either intracavitary talc or bleomycin. For 25 assessable treatments in 22 patients, recurrence of effusion was observed in 5 of 15 (33 per cent) of the bleomycin group compared with none in the talc group. It is concluded that talc is superior to bleomycin in controlling pleural effusions secondary to breast carcinoma, but bleomycin may have a role in patients unfit for general anaesthesia or with extensive disease elsewhere.", "In a controlled clinical trial we investigated 102 patients with malignant pleural effusion due to breast cancer, lung cancer, ovarian cancer and other tumors to compare the therapeutic effect and adverse events of pleurodesis with bleomycin (BMC) or mitoxantrone (MIT) via chest tube. Finally 96 patients had been treated according to the protocol. Age, gender, Broca index, performance score or distribution of primary tumors were not statistically different between the BMC (n = 49) or MIT group (n = 47). We found no differences between intention-to-treat and according-to-protocol groups as well. 30 days after BMC pleurodesis we found remissions of the effusion in 91% of patients (complete remission [CR] 51%, partial remission [PR] 40%), after 90 days in 83% (40% CR, 43% PR). 30 days after MIT instillation we found remission in 73% of patients (35% CR, 38% PR), after 90 days in 61% (29% CR, 32% PR) (30 and 90 days: p < 0.05). Adverse events were not different between BMC and MIT group. BMC is a safe and effective sclerosing agent for pleurodesis via chest tube.", "Forty-one patients with malignant pleural effusions secondary to breast cancer were randomly allocated to treatment with either intracavitary talc or intracavitary tetracycline. Of 33 evaluable patients, radiological control was achieved in 11/12 (92%) of the talc group compared with 10/21 (48%) of the tetracycline group (P = 0.022). Intracavitary talc provides effective palliation of metastatic pleural effusions secondary to breast cancer.", "From 11/87 until 7/90 103 patients entered a prospective randomized trial on the treatment of malignant pleural effusions (MPE) with intrapleural mitoxantrone versus placebo (pleural tube alone with instillation of isotonic NaCl). Our data suggest no statistically significant difference between the two arms with respect to response and response duration. There is no influence on survival time. The toxicity is moderate, with only fever occurring more often in the mitoxantrone arm. We recommend performance of pleurodesis in patients with MPE first by sufficient drainage with a tube of 16-20 char. Only in instances of failure it is necessary to add sclerosing agents such as tetracycline, etc.", "Pleural sclerosis after tube thoracostomy was performed in 40 patients with malignant pleural effusions. The patients were randomly allocated to intrapleural therapy with tetracycline or mechlorethamine. Follow up was obtained on each patient to determine if a symptomatic effusion recurred. The response was classified as a complete or partial response and failure. (Complete response: complete lack of reaccumulation of pleural fluid for at least 60 days. Partial response: small pleural effusion asymptomatic not requiring further treatment for at least 60 days. Failure: all other cases). Tetracycline produced complete or partial control of the effusion in 16 of 20 trials for a duration of 6.1 +/- 4.1 months (range 2-14 months). Mechlorethamine produced control of the effusion in 12 of 20 trials for a duration of 4.4 +/- 1 months (range 2-8 months). These findings indicate that intracavitary tetracycline is a more effective treatment than intracavitary mechlorethamine for the control of neoplastic pleural effusion.", "Malignant pleural effusions are a common problem for patients with metastatic disease. Most patients are treated with tube thoracostomy and sclerotherapy, although there remains no standard approach. The purpose of this study was to compare the efficacy of bleomycin with doxycycline sclerotherapy for the treatment of malignant pleural effusions using small-bore catheters.\n All patients with a symptomatic malignant pleural effusion referred for chest tube drainage and sclerotherapy over a 2-year period were considered eligible. Using image guidance, a 14F self-retaining catheter was inserted into the pleural space and connected to continuous wall suction. When drainage fell below 200 mL/d, patients were randomized to 60 U of bleomycin or 500 mg of doxycycline sclerotherapy. Response at 30 days was determined.\n One hundred six patients were enrolled in the study. Fifteen men (29%) and 37 women (71%) with a mean age of 57 years received bleomycin sclerotherapy. Twenty-one of the 29 patients (72%) alive and evaluable at 30 days had successful sclerotherapy. Twenty-three men (43%) and 31 women (57%) with a mean age of 61 years received doxycycline sclerotherapy. Twenty-three of the 29 patients (79%) alive and evaluable at 30 days had successful sclerotherapy. There was no significant difference in response rates between doxycycline and bleomycin (p=0.760).\n These data continue to support a role for small-bore chest drainage and sclerotherapy, although there was no significant difference in 30-day response rates between doxycycline and bleomycin.", "Both bleomycin and tetracycline have been suggested as the sclerosing agent of choice in the management of malignant pleural effusions. To determine if one drug is superior to the other in this role, patients with malignant pleural effusions were randomly assigned to receive either bleomycin or tetracycline in the previously evacuated pleural space through a thoracostomy tube. Following instillation of the assigned agent, the tube was clamped for 8 hours and then reattached to suction. When the chest tube drainage had slowed to less than 40 ml in a 24-hour period or if 7 days had passed, the tube was removed. Pleural sclerosis was attempted 42 times in 34 patients. No statistically significant differences were found between the two treatment groups when prevention of effusion reaccumulation and time to removal of the chest tube (efficiency) were compared. Side effects including pleural pain and fever, occurred with both agents, but were manageable. Since one drug was not clearly superior to the other, and bleomycin is more costly, we suggest that tetracycline rather than bleomycin be used when pleural sclerosis is needed to manage malignant pleural effusions.", "Intrapleural administration of fibrinolytic agents has been shown to be effective and safe in the treatment of loculated parapneumonic pleural effusions. However, controlled studies of the possible role of the activity of urokinase (UK) through the volume effect are lacking. We therefore investigated the hypothesis that UK is effective through the lysis of pleural adhesions and not through the volume effect. Thirty-one consecutive patients with multiloculated pleural effusions were randomly assigned to receive either intrapleural UK (15 patients) or normal saline (NS) (16 patients) for 3 d, in a double-blind manner. All patients had inadequate drainage through a chest tube (< 70 ml/24 h). UK was given daily through the chest tube in a dose of 100.000 IU diluted in 100 ml of NS. Controls were given the same volume of NS intrapleurally. Response was assessed by clinical outcome, fluid drainage, chest radiography, pleural ultrasonography (US) and/or computed tomography (CT). Clinical and radiographic improvement was noted in all but two patients in the UK group but in only four in the control group. The net mean volume drained during the 3-d treatment period was significantly greater in the UK group (970 +/- 75 ml versus 280 +/- 55 ml, p < 0.001). Pleural fluid drainage was complete in 13 (86.5%) patients in the UK group (two patients were treated through video-assisted thoracoscopy) but in only four (25%) in the control group. Twelve patients in the control group were subsequently treated with UK and six of them had complete drainage; the remaining six patients had complete drainage after video-assisted thoracoscopy. Our results suggest that UK is effective in the treatment of loculated pleural effusions through the lysis of pleural adhesions and not through the volume effect.", "Treatment of patients with malignant pleural effusions is mostly palliative. Tetracycline and bleomycin are the two most commonly used agents for the treatment of pleurodesis. In this study, the authors used a combination of the two drugs for this particular purpose.\n Sixty patients with massive malignant pleural effusions were divided in 3 equal groups in a simple randomized manner. Tetracycline (20 mg/kg [maximum of 2 g] in 50 mL of normal saline) was administered through a chest tube in Group 1. Group 2 received bleomycin (1 U/kg [maximum of 60 U] in 50 mL of normal saline). Group 3 received the above 2 preparations (tetracycline, 20 mg/kg [maximum of 2 g] in 40 mL of normal saline and bleomycin, 1 U/kg [maximum of 60 U] in 30 mL of normal saline) instilled one after the other, while the chest tube was clamped for 5 minutes in the interim. Follow-up examinations were performed at 7 days, 30 days, 60 days, 90 days, and 6 months.\n There was no significant difference in the complete response rate of the 3 groups during the first 4 months. At the end of the study, Group 3 had a significantly higher complete response rate (70%) compared with Groups 1 and 2 (35% and 25%, respectively) (P = 0.02).\n The response to use of a combination of bleomycin and tetracycline for the treatment of patients with pleurodesis is superior to that achieved by either of these agents used alone.", "Intrapleural instillation of tetracycline (TCN) has been shown to be effective in preventing the recurrence of malignant pleural effusions. Although the precise mechanism of action is unknown, it has been postulated that the pH of the TCN solution may be an important factor. Thirty patients with malignant pleural effusions were randomized in a double-blind trial to receive intrapleural administration of either 500 mg of tetracycline in solution (pH = 2.8) or a solution of similar pH and appearance. All patients had chest tube drainage of their effusion. There were 24/30 patients evaluable. There were 9/13 patients in the TCN group and 1/9 patients in the control group who had no reaccumulation of fluid (P less than 0.05). These results would suggest that the efficacy of TCN as a sclerosing agent is not related to its acidic pH and that intrapleural TCN is more effective than chest tube drainage alone for control of malignant effusions.", "To assess the efficacy and safety of polidocanol (POL) in comparison to sodium tetradecyl sulphate (STS) and isotonic saline (placebo) for sclerotherapy of telangiectases or reticular veins by means of standardized digital imaging system, independent medical observers and detailed monitoring.\n Of 316 randomized patients, 160 with telangiectases were randomly assigned to 0.5% POL, 1% STS or placebo, and 156 with reticular veins received 1% POL, 1% STS or placebo. Veins selected for injection were clearly visible telangiectases or reticular veins in a predefined treatment area (10x10 cm). Exact retrieval of the location was guaranteed by a newly established digital imaging system. Images were taken before first injection and 12 and 26 weeks after the last of three possible injection visits, and evaluated by the investigator and two blinded independent observers. The detailed safety monitoring included ultrasound screening for 'silent' deep vein thrombosis, electrocardiograms and clinical laboratory tests.\n POL demonstrated a statistically significant superiority versus placebo (P < 0.0001) for the primary criterion 'improvement of veins'. Significantly more patients were satisfied with POL at 12 or 26 weeks (84%, 88%) compared to STS (64%, 63%; P < 0.0001) and placebo (14%, 11%; P < 0.0001). POL was safe and well tolerated apart from expected local symptoms at the injection site.\n Sclerotherapy of telangiectases and reticular veins with detergent-like sclerosants such as polidocanol (POL) or sodium tetradecyl sulphate (STS) is a well-established technique. However, evidence from clinical trials comparing these substances with a non-active solution is sparse and does not live up to expectations of modern clinical trial concepts necessary for authorisation purposes. The presented multicentre EASI study fulfils these requirements and clearly demonstrates that Sclerotherapy of C1 veins with POL is highly effective and deserves the adjunct 'gold standard'.", "Between December 1985 and August 1988, there were 115 patients at 13 centers who were entered on a randomized comparison of tetracycline and bleomycin for treatment of malignant pleural effusions. Fifteen patients were not treated, primarily due to rapid progression of systemic cancer. Fifteen patients entered on a high-dose regimen of bleomycin (120 units) were excluded from this analysis (following early closure of that arm), leaving 85 patients randomized to low-dose bleomycin (60 units; 44 patients) or tetracycline (1 g; 41 patients). Patients were required to have a cytologically positive pleural effusion, good performance status (0, 1, or 2), lung reexpansion following tube thoracostomy with drainage rates of 100 ml/24 or less, no prior intrapleural therapy, no prior systemic bleomycin therapy, no chest irradiation, and no recent (four weeks) change in systemic therapy. A total of 11 patients (five with bleomycin and six with tetracycline) were not evaluable due to technical problems with tube drainage (one), loss to follow-up (two), sudden death due to pulmonary embolus (one), and rapid progression of systemic disease (seven). There were no clinically significant differences in demographic factors, primary site, performance status, or presence of metastases other than pleural effusion. Overall survival did not differ between the two groups. Median time to recurrence or progression of the effusion was 32 days for tetracycline-treated patients and at least 46 days for bleomycin-treated patients (p = 0.037). The recurrence rate within 30 days of instillation was 36 percent (10/28) with bleomycin and 67 percent (18/27) with tetracycline (p = 0.023) (not all patients were restudied in the first 30 days). By 90 days the corresponding recurrence rates were 30 percent (11/37) for bleomycin and 53 percent (19/36) for tetracycline (p = 0.047). Toxicity was similar between groups.", "Tuberculous pleurisy can result in pleural fibrosis, calcification and thickening. To prevent these complications, corticosteroids are frequently used in addition to antituberculous drugs; however, new therapeutic regimens can control the disease and minimise the sequelae, and there is no convincing evidence of the benefit of the use of corticosteroids as adjuvant therapy.\n Patients received isoniazid 5 mg/kg and rifampicin 10 mg/kg daily for six months. Additionally, they were randomly assigned to a double blind treatment with either prednisone (1 mg/kg/day for 15 days and then tapering off) or placebo during the first month of treatment. Different clinical, radiological, and functional parameters were evaluated to assess the effect of corticosteroids.\n Fifty seven patients received prednisone and 60 placebo. At the end of the treatment the clinical outcome, the rate of reabsorption of the pleural fluid, the pleural sequelae, as well as lung capacity were similar in both groups.\n Corticosteroids do not influence the clinical outcome or the development of long term pleural sequelae in tuberculous pleurisy.", "Although several studies on tuberculous (TB) pleurisy suggest that the addition of corticosteroids to anti-TB therapy may have beneficial effects, these agents are not used routinely. To assess the effects of short-term oral prednisone therapy in TB pleurisy, 74 patients were randomly assigned in a double-blind fashion to treatment with either placebo or prednisone at a dose of 0.75 mg/kg/d for up to 4 weeks with gradual reduction over an additional 2 weeks. All subjects received a standard 3-drug anti-TB chemotherapy regimen for 6 months. TB pleurisy was diagnosed by histologic study and/or culture of pleural biopsy specimens obtained at thoracoscopy. Complete drainage of the effusion was performed simultaneously. Outcome measures were assessed periodically for 24 weeks, including indexes of morbidity and pleural thickening. After randomization, four patients were excluded from the final analysis. Of the 70 patients analyzed, 34 received prednisone and 36 received placebo. Demographic and clinical characteristics of the treatment groups were comparable at the time of hospital admission. Although a statistically significant improvement in symptoms occurred earlier in the prednisone group (8 weeks) than in the placebo group (12 weeks), between-group comparison showed no significant differences at any of the follow-up evaluations. The proportion of subjects in the prednisone group (53.1%) with residual pleural thickening at 6 months did not differ significantly from that of the placebo group (60%). Pleural effusions did not recur in any of the patients. Initial complete drainage of the effusion was associated with greater symptomatic improvement than any subsequent therapy. We conclude that standard anti-TB therapy and early complete drainage is adequate for the treatment of TB pleurisy. The addition of short-term oral prednisone therapy neither results in clinically relevant earlier symptom relief nor confers a beneficial effect on residual pleural thickening.", "Concurrent platinum etoposide chemotherapy given in combination with hyperfractionated thoracic radiation therapy (HTRT) in limited disease (LD) small cell lung cancer (SCLC) is associated with a high response rate and significant prolongation of survival. Given these results, the Hellenic Cooperative Oncology Group (HeCOG) performed a multicenter randomized phase II study in patients with LD SCLC to evaluate the timing of HTRT (early vs. late) when given concurrently with chemotherapy.\n To be eligible for the study, patients were required to have histologically or cytologically proven LD SCLC, confined to one hemithorax and/or ipsilateral mediastinal or supraclavicular lymphnodes and absence of pleural effusion or controlateral supraclavicular lymphnode involvement. Moreover, patients had to have a good performance status and adequate haematological, liver and renal function. Patients with LD SCLC were randomized to receive HTRT either concurrently with the first (Group A) or with the fourth (Group B) cycle of chemotherapy. Chemotherapy consisted of carboplatin administered at an AUC of six given as an i.v. 1-hour-infusion immediately followed by etoposide at a dose of 100 mg/m2 i.v. as a two-hour infusion for three consecutive days every three weeks up to a total of six cycles. Prophylactic cranial irradiation was also given to patients achieving a complete response.\n 42 and 39 patients, were eligible for efficacy evaluation in group A and B respectively. The overall response rate was 76% in group A and 92.5% in group B (P = 0.07) with a complete response rate of 40.5% and 56.5%, respectively. After a median follow-up of 35 months, time to progression was 9.5 months in group A and 10.5 in group B (NS) while overall median survival was 17.5 and 17 months respectively (NS). The 2-year survival was 36% in group A and 29% in group B (NS) and the 3-year survival 22% and 13%, respectively (NS). The distant relapse rate was 38% in group A and 61% in group B (P = 0.046). Severe grade 3 4 anemia was recorded in 19% of group A and 12.5% of group B (NS), while severe leucopenia was recorded in 35.5% and 20.5% (P = 0.09) and neutropenic fever in 5% and 2.5% (NS), respectively. Severe thrombocytopenia did not differ significantly between the two treatment groups being 21.5% and 23%, respectively. Severe grade 2-3 esophageal toxicity was 19% in group A and 23% in group B (NS), while grade 3 lung toxicity was 5% and 7.5% (NS), respectively. No toxicity-related deaths were recorded.\n Concurrent administration of HTRT with carboplatin etoposide is associated with a high response and survival rate. Although a trend for higher response rate was recorded in the group of patients who received late HTRT, the overall median, 2-year and 3-year survival rates did not differ significantly between the two treatment groups. The toxicity of this promising therapeutic approach was acceptable. Comparative phase III studies with an adequate number of patients are recommended in order to answer this question." ]	The available evidence supports the need for chemical sclerosants for successful pleurodesis, the use of talc as the sclerosant of choice, and thoracoscopic pleurodesis as the preferred technique for pleurodesis based on efficacy. There was no evidence for an increase in mortality following talc pleurodesis.
CD005461	[ "17346475", "9763048", "18450604", "17010115", "12946338" ]	[ "A randomized controlled trial of a bedside partogram in the active management of primiparous labour.", "Partogram action line study: a randomised trial.", "A behavioral intervention to improve obstetrical care.", "Cluster randomised trial of an active, multifaceted educational intervention based on the WHO Reproductive Health Library to improve obstetric practices.", "A randomised controlled trial of admission electronic fetal monitoring in normal labour." ]	[ "The partogram is a pictorial representation of the progress of labour, used in an effort to enhance early recognition of dystocia and help avoid Caesarean section (CS). The objective of this study was to evaluate the effect of partogram use on the CS and obstetric intervention rates.\n We conducted a randomized controlled trial of use of the partogram in 1932 primiparous women with uncomplicated pregnancies at term. Patients were randomly assigned to one of two groups: the standard group, who had the progress of labour charted in written notes, or the partogram group, whose progress in labour was recorded using a bedside graphical partogram as well as in written notes. Outcomes were stratified according to whether labour was spontaneous or induced and whether membranes were initially intact or ruptured. The primary outcome was the rate of CS; secondary outcome measures were rates of obstetric intervention for dystocia.\n There was no significant difference between the groups in rates of CS (partogram 24%, standard notes 25%), rates of other interventions, amniotomy, oxytocin use, or the mean cervical dilatation in labour.\n In this study, the use of a partogram without a mandatory management of labour protocol had no effect on rates of CS or other intrapartum interventions in healthy primiparous women at term.", "To assess the effect of three different partograms on caesarean section and maternal satisfaction.\n Prospective randomised clinical trial.\n Regional teaching hospital in North West of England.\n Nine hundred and twenty-eight primigravid women with uncomplicated pregnancies who presented in spontaneous labour at term.\n The women were randomised to have their progress of labour recorded on a partogram with an action line 2, 3 or 4 hours to the right of the alert line. If the progress reached the action line, a diagnosis of prolonged labour was made. Prolonged labour was managed according to the standard ward protocol.\n Primary: Caesarean section rate and maternal satisfaction; secondary: need for augmentation, duration of labour, analgesia, cord blood gas analysis, postpartum haemorrhage, number of vaginal examinations, Apgar score and admission to special care baby unit.\n Caesarean section rate was lowest when labour was managed using a partogram with a 4-hour action line. The difference between the 3- and 4-hour partograms was statistically significant (OR 1 8, 95% CI 1.1-3.2), but the difference between 2 and 4 hours was not (OR 1.4, 95% CI 0.8-2.4). The women in the 2-hour arm were more satisfied with their labour when compared to the women in the 3-hour (P < 00001) and 4-hour (P <00001) arm.\n Our data suggest that women prefer active management of labour. It is possible that partograms which favour earlier intervention are associated with higher caesarean section rate. As the evidence on which to base the choice of partograms remains inconclusive further research is required.", "Implementation of evidence-based obstetrical practices remains a significant challenge. Effective strategies to disseminate and implement such practices are needed.\n We randomly assigned 19 hospitals in Argentina and Uruguay to receive a multifaceted behavioral intervention (including selection of opinion leaders, interactive workshops, training of manual skills, one-on-one academic detailing visits with hospital birth attendants, reminders, and feedback) to develop and implement guidelines for the use of episiotomy and management of the third stage of labor or to receive no intervention. The primary outcomes were the rates of prophylactic use of oxytocin during the third stage of labor and of episiotomy. The main secondary outcomes were postpartum hemorrhage and birth attendants' readiness to change their behavior with regard to episiotomies and management of the third stage of labor. The outcomes were measured at baseline, at the end of the 18-month intervention, and 12 months after the end of the intervention.\n The rate of use of prophylactic oxytocin increased from 2.1% at baseline to 83.6% after the end of the intervention at hospitals that received the intervention and from 2.6% to 12.3% at control hospitals (P=0.01 for the difference in changes). The rate of use of episiotomy decreased from 41.1% to 29.9% at hospitals receiving the intervention but remained stable at control hospitals, with preintervention and postintervention values of 43.5% and 44.5%, respectively (P<0.001 for the difference in changes). The intervention was also associated with reductions in the rate of postpartum hemorrhage of 500 ml or more (relative rate reduction, 45%; 95% confidence interval [CI], 9 to 71) and of 1000 ml or more (relative rate reduction, 70%; 95% CI, 16 to 78). Birth attendants' readiness to change also increased in the hospitals receiving the intervention. The effects on the use of episiotomy and prophylactic oxytocin were sustained 12 months after the end of the intervention.\n A multifaceted behavioral intervention increased the prophylactic use of oxytocin during the third stage of labor and reduced the use of episiotomy. (ClinicalTrials.gov number, NCT00070720 [ClinicalTrials.gov]; Current Controlled Trials number, ISRCTN82417627 [controlled-trials.com].).\n Copyright 2008 Massachusetts Medical Society.", "We conducted a trial to evaluate the effect of an active, multifaceted educational strategy to promote the use of the WHO Reproductive Health Library (RHL) on obstetric practices.\n Cluster randomised trial. The trial was assigned the International Standardised Randomised Controlled Trial Number ISRCTN14055385.\n Twenty-two hospitals in Mexico City and 18 in the Northeast region of Thailand.\n The intervention consisted primarily of three interactive workshops using RHL over a period of 6 months. The focus of the workshops was to provide access to knowledge and enable its use. A computer and support for using both the computer and RHL were provided at each hospital. The control hospitals did not receive any intervention.\n The main outcome measures were changes in ten selected clinical practices as recommended in RHL starting approximately four to six months after the third workshop. Clinical practice data were collected at each hospital from 1000 consecutively delivered women or for a 6-month period whichever was reached sooner.\n The active, multifaceted educational intervention we employed did not affect the ten targeted practices in a consistent and substantive way. Iron/folate supplementation, uterotonic use after birth and breastfeeding on demand were already frequently practiced, and we were unable to measure external cephalic version. Of the remaining six practices, selective, as opposed to routine episiotomy policy increased in the intervention group (difference in adjusted mean rate = 5.3%; 95% CI -0.1 to 10.7%) in Thailand, and there was a trend towards an increased use of antibiotics at caesarean section in Mexico (difference in adjusted mean rate = 19.0%; 95% CI: -8.0 to 46.0%). There were no differences in the use of labour companionship, magnesium sulphate use for eclampsia, corticosteroids for women delivering before 34 weeks and vacuum extraction. RHL awareness (24.8-65.5% in Mexico and 33.9-83.3% in Thailand) and use (4.8-34.9% in Mexico and 15.5-76.4% in Thailand) increased substantially after the intervention in both countries.\n The multifaceted, active strategy to provide health workers with the knowledge and skills to use RHL to improve their practice led to increased access to and use of RHL, however, no consistent or substantive changes in clinical practices were detected within 4-6 months after the third workshop.", "To test the hypothesis that the use of admission Electronic Fetal Monitoring (EFM) for healthy pregnant women in spontaneous labour would result in an increase in continuous EFM when compared to women who have had no admission EFM.\n A randomised controlled trial.\n The Midwives Birth Unit in Glasgow Royal Maternity Hospital, a major urban teaching hospital with approximately 5000 births per year.\n Healthy pregnant women admitted in normal labour, deemed low risk based on the midwives' birth unit admission criteria.\n Women were randomly allocated either to receive a routine 20-minute period of EFM at the time of admission (control group), or to receive no routine admission EFM (study group).\n Primary study outcomes, use of continuous EFM; and use of EFM additional to the admission test. Secondary outcomes: artificial rupture of membranes, use of fetal scalp electrode, fetal blood sample, syntocinon, epidural analgesia, number of vaginal examinations, rate of transfer to labour ward, and reason for transfer.\n There was no statistically significant difference between the groups for use of continuous monitoring, but significantly more women in the control group did receive additional EFM. There was no statistically significant difference between groups for any of the interventions studied.\n The use of admission EFM did not in itself lead to a cascade of intervention. Other factors including setting of care and philosophy of caregivers may have an effect on the rate of intervention in labour." ]	On the basis of the findings of this review, we cannot recommend routine use of the partogram as part of standard labour management and care. Given the fact that the partogram is currently in widespread use and generally accepted, it appears reasonable, until stronger evidence is available, that partogram use should be locally determined. Further trial evidence is required to establish the efficacy of partogram use.
CD003387	[ "11431238", "9167520", "11780880" ]	[ "Right prefrontal repetitive transcranial magnetic stimulation in obsessive-compulsive disorder: a double-blind, placebo-controlled study.", "Effect of prefrontal repetitive transcranial magnetic stimulation in obsessive-compulsive disorder: a preliminary study.", "Right versus left prefrontal transcranial magnetic stimulation for obsessive-compulsive disorder: a preliminary investigation." ]	[ "The efficacy of repetitive transcranial magnetic stimulation (rTMS) of the right prefrontal cortex for patients with obsessive-compulsive disorder (OCD) was studied under double-blind, placebo-controlled conditions.\n Patients were randomly assigned to 18 sessions of real (N=10) or sham (N=8) rTMS. Treatments lasted 20 minutes, and the frequency was 1 Hz for both conditions, but the intensity was 110% of motor threshold for real rTMS and 20% for the sham condition.\n No significant changes in OCD were detected in either group after treatment. Two patients who received real rTMS, with checking compulsions, and one receiving sham treatment, with sexual/religious obsessions, were considered responders.\n Low-frequency rTMS of the right prefrontal cortex failed to produce significant improvement of OCD and was not significantly different from sham treatment. Further studies are indicated to assess the efficacy of rTMS in OCD and to clarify the optimal stimulation characteristics.", "Prefrontal mechanisms are implicated in obsessive-compulsive disorder. The authors investigated whether prefrontal repetitive transcranial magnetic stimulation influenced obsessive-compulsive disorder symptoms.\n Twelve patients with obsessive-compulsive disorder were given repetitive transcranial magnetic stimulation (80% motor threshold, 20 Hz/2 seconds per minute for 20 minutes) to a right lateral prefrontal, a left lateral prefrontal, and a midoccipital (control) site on separate days, randomized. The patients' symptoms and mood were rated for 8 hours afterward.\n Compulsive urges decreased significantly for 8 hours after right lateral prefrontal repetitive transcranial magnetic stimulation, but there were nonsignificant increases in compulsive urges after repetitive transcranial magnetic stimulation of the midoccipital site. A shorter-lasting (30 minutes), modest, and nonsignificant reduction in compulsive urges occurred after left lateral prefrontal repetitive transcranial magnetic stimulation. Mood improved during and 30 minutes after right lateral prefrontal stimulation.\n These preliminary results suggest that right prefrontal repetitive transcranial magnetic stimulation might affect prefrontal mechanisms involved in obsessive-compulsive disorder.", "There is preliminary evidence that repetitive transcranial magnetic stimulation (rTMS) may be useful for the treatment of obsessive-compulsive disorder (OCD), but no definitive study has been published, and the effect of laterality of stimulation is uncertain.\n Subjects (N = 12) with resistant OCD were allocated randomly to either right or left prefrontal rTMS daily for 2 weeks and were assessed by an independent rater at 1 and 2 weeks and 1 month later.\n Subjects had an overall significant improvement in the obsessions (p < .01), compulsions (p < .01), and total (p < .01) scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) after 2 weeks and at 1-month follow-up. This improvement was significant for obsessions (p < .05) and tended to significance for total Y-BOCS scores (p = .06) after correction for changes in depression scores on the Montgomery-Asberg Depression Rating Scale. There was no significant difference between right- and left-sided rTMS on any of the parameters examined. Two subjects (33%) in each group showed a clinically significant improvement that persisted at I month but with relapse later in I subject.\n A proportion (about one quarter) of patients with resistant OCD appear to respond to rTMS to either prefrontal lobe, although in the absence of a sham treatment group in this study, we cannot rule out the possibility of this being a placebo response. This treatment warrants further investigation to better establish its efficacy and examine the best parameters for response." ]	There are currently insufficient data from randomised controlled trials to draw any conclusions about the efficacy of transcranial magnetic stimulation in the treatment of obsessive-compulsive disorder.
CD000177	[ "3067105", "3901421", "3890279" ]	[ "[Use of prostacyclin in patients with ischemic stroke. A double-blind method II].", "Double-blind controlled trial of the therapeutic effects of prostacyclin in patients with completed ischaemic stroke.", "Double-blind controlled trial of prostacyclin in cerebral infarction." ]	[ "Thirty patients with acute ischaemic stroke were allocated randomly into a group treated with prostacyclin and a group receiving placebo. The treatment was started 24 to 72 hours after the onset of stroke. Prostacyclin sodium (Wellcome, U.K. or Chinoin, HPR) or its solvent (glycine buffer) were administered intravenously once daily during 2 weeks in 6-hour infusions. Prostacyclin was infused at rates of 2.5-5.0 ng/kg/min. Statistically significant improvement appeared from the second day on in the prostacyclin group, and only from the eighth day on in the placebo group. However, the final improvement was not statistically different between these groups.", "In a pilot study, 26 patients with acute completed strokes (48 hours to 5 days after cerebral infarction) were randomly assigned to the prostacyclin (PGI2) or placebo groups. PGI2 sodium salt (Epoprostenol, Wellcome Research Laboratories and Upjohn Company) or its solvent (glycine buffer) were infused into the subclavian vein for six-hour periods in five courses separated by six-hour intervals. Prostacyclin was administered at a rate of 2.5-5.0 ng/kg/min. A significant alleviation of neurological deficits occurred 6 and 54 hours after the treatment in patients receiving prostacyclin. This improvement lost its statistical significance at the end of a two-week observation period. It is concluded that further modified controlled studies are required to evaluate the therapeutic usefulness of PGI2 in the treatment of patients with cerebral ischaemia.", "Thirty-two patients with acute cerebral infarction received either prostacyclin or placebo intermittently for 65 hours. Pulse and blood pressure were not altered by prostacyclin. After infusion there was no change in infarct volume or cerebral blood flow in either group. After normalisation for starting values, age and site of cerebral infarction there was a greater than 10% improvement in speech in the prostacyclin group, but minimal changes in neurological score or disability status. Age is related to neurological score at 14 days after stroke by decreasing improvement by 6.8% for each additional 10 years. This study has not been able to demonstrate that prostacyclin is effective in the treatment of ischaemic stroke, but due to the sample size the chance of proving this statistically (the power) was small. Similarly any conclusion that prostacyclin is not effective may be wrong because of the Type II error probability being high." ]	Too few patients have been studied in randomised trials to allow conclusions to be drawn about the effect of prostacyclin treatment on survival of people with acute stroke.
CD006115	[ "9197912", "1681680", "1683336", "10732655", "16633144", "10676820", "18562423", "1978371", "16810506", "2668784", "2883680", "9989566", "8215814", "12900300", "11163780", "11823268", "16585434", "1683334" ]	[ "Paroxetine efficacy in the treatment of generalized anxiety disorder.", "Zuclopenthixol decanoate and haloperidol decanoate in chronic schizophrenia: a double-blind multicentre study.", "[Zotepine versus perazine in patients with paranoid schizophrenia: a double-blind controlled trial of its effectiveness].", "Prior benzodiazepine use and buspirone response in the treatment of generalized anxiety disorder.", "A 24-week randomized study of olanzapine versus ziprasidone in the treatment of schizophrenia or schizoaffective disorder in patients with prominent depressive symptoms.", "Efficacy and safety of lesopitron in outpatients with generalized anxiety disorder.", "Efficacy and tolerability of ziprasidone versus risperidone as augmentation in patients partially responsive to clozapine: a randomised controlled clinical trial.", "Efficacy and safety of a putative anxiolytic agent: ipsapirone.", "The neurocognitive effects of aripiprazole: an open-label comparison with olanzapine.", "A placebo-controlled, randomized, double-masked, variable dosage, clinical trial of azathioprine with and without methylprednisolone in multiple sclerosis.", "Comparison of efficacy of zotepine and thiothixene in schizophrenia in a double-blind study.", "Clozapine and risperidone in chronic schizophrenia: effects on symptoms, parkinsonian side effects, and neuroendocrine response.", "Antidepressants for the treatment of generalized anxiety disorder. A placebo-controlled comparison of imipramine, trazodone, and diazepam.", "Comparative efficacy and safety of atypical and conventional antipsychotic drugs in first-episode psychosis: a randomized, double-blind trial of olanzapine versus haloperidol.", "Double-blind comparison of olanzapine versus clozapine in schizophrenic patients clinically eligible for treatment with clozapine.", "Clozapine, olanzapine, risperidone, and haloperidol in the treatment of patients with chronic schizophrenia and schizoaffective disorder.", "Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment.", "[Effectiveness and tolerance of zotepine in a double-blind comparison with perazine in schizophrenic patients]." ]	[ "Recently, there has been a renewed interest in alternatives to the benzodiazepines for the treatment of generalized anxiety disorder (GAD). The aim of the present study was to compare the efficacy of paroxetine vs. imipramine and 2'-chlordesmethyldiazepam in 81 patients with a DSM-IV diagnosis of GAD. Approximately two-thirds of the patients who completed the study improved greatly or moderately on all three active drugs. During the first 2 weeks of treatment, 2'-chlordesmethyldiazepam treatment resulted in the greatest improvement in anxiety ratings. Both paroxetine and imipramine treatment resulted in more improvement than 2'-chlordesmethyldiazepam by the fourth week of treatment. Paroxetine and imipramine affect predominantly psychic symptoms, whereas 2'-chlordesmethyldiazepam affects predominantly somatic symptoms. Our results suggest that paroxetine is effective for the treatment of GAD.", "Zuclopenthixol decanoate (ZPT-D) and haloperidol decanoate (HAL-D) were compared in the maintenance treatment of chronic schizophrenic patients. All patients were treated with either ZPT-D or HAL-D for at least 3 months and were then randomly allocated to treatment with either ZPT-D (100-600 mg every 4 weeks) or HAL-D (38-200 mg every 4 weeks) for 9 months. Sixty-four patients entered the study. Three patients were only assessed at baseline. Four patients in the HAL-D group were withdrawn because of deterioration. One patient in the ZPT-D group committed suicide. Fifty-six patients completed the trial. The assessment programme comprised Clinical Global Impressions by psychiatrists and nurses, the Brief Psychiatric Rating Scale (BPRS), Montgomery-Asberg Depression Rating Scale (MADRS), UKU Side Effect Scale and Simpson-Angus Scale, Ratings were made at baseline and after 12, 24 and 36 weeks of treatment. The severity of illness scores remained almost constant. The only between-group difference was recorded at month 6 in favour of ZPT-D. The BPRS total scores were reduced significantly in both groups with no between-group differences. The depression scores on the MADRS were very low. Both treatments caused few and mild side effects according to the UKU Side Effect Scale and the Simpson-Angus scale, and there were no significant differences between the groups. Both ZPT-D and HAL-D seem to be effective in the maintenance treatment of chronic schizophrenic patients and cause few side effects. The injections of ZPT-D and HAL-D can be given at 4-week intervals.", "The dibenzothiepine zotepine is a new potential \"atypical\" neuroleptic exhibiting powerful antiserotonergic and antidopaminergic properties. The efficacy of zotepine was evaluated in a double-blind controlled trial versus the tricyclic neuroleptic perazine in 41 patients suffering mainly from the paranoid-hallucinatory type of schizophrenia. The key outcome variable was the extent of mental disturbance as defined by the total score of the BPRS. Additional outcome variables were GAS and CGI. In addition, adverse reactions and extrapyramidal side effects were assessed according to the FSUCL scale and the Gerlach and AIMS rating scale, respectively. Additional variables recorded were blood pressure, heart rate and routine laboratory parameters as well as electrocardiogram and electroencephalogram. In the first two days, standard equivalent doses of both drugs were administered. Thereafter, doses were administered as required. The efficacy of both substances was compared after 7, 14 and 28 days of treatment. Both drugs showed a similar antipsychotic efficacy. Under zotepine treatment a 55% improvement of the BPRS total score was observed while perazine led to a 41% BPRS score reduction. After 7 days the zotepine group was significantly more improved than the perazine group, possibly due to a dosing effect in the perazine group. In the zotepine group, fewer adverse reactions and a better benefit/risk index were observed although the differences between the two treatment groups did not reach levels of statistical significance. There were no drug-specific abnormal laboratory findings. Thus, in the present study there was no significant difference between zotepine and perazine with respect to antipsychotic efficacy and side-effect rates. However, zotepine showed a trend to a better benefit/risk index at the end of treatment.", "An earlier preliminary report suggested that prior treatment with benzodiazepines might predict a reduced response to buspirone in patients diagnosed with generalized anxiety disorder (GAD). To confirm or refute this hypothesis, the present data analysis was conducted.\n One large data set (N = 735) of GAD patients (DSM-III) treated with buspirone, a benzodiazepine, and a placebo was analyzed by dividing all patients into 3 prior benzodiazepine (BZ) treatment groups: no prior BZ treatment, recent (< 1 month) BZ treatment, and remote (> or = 1 month) BZ treatment. Using an intent-to-treat last-observation-carried-forward (LOCF) data set, acute 4-week treatment response was assessed in terms of clinical improvement, attrition, and adverse events as a function of these 3 prior benzodiazepine treatment groups.\n Patient attrition was significantly higher (p < .05) in the recent BZ treatment group than in the remote and no prior BZ treatment groups with lack of efficacy given as the primary reason by patients receiving buspirone but not benzodiazepine or placebo. In the buspirone group, adverse events occurred more frequently in the recent BZ treatment group than in the remote BZ treatment and no prior BZ treatment groups. Finally, clinical improvement with buspirone was similar to benzodiazepine improvement in the no prior BZ treatment and remote BZ treatment groups, but less than benzodiazepine improvement in the recent BZ treatment group, leading to the smallest buspirone/placebo differences in improvement in the recent BZ treatment group.\n These data suggest that the initiation of buspirone therapy in GAD patients who have only recently terminated benzodiazepine treatment should be undertaken cautiously and combined with appropriate patient education.", "The objective of this study is to compare olanzapine with ziprasidone therapy in patients with schizophrenia or schizoaffective disorder and experiencing depressive symptoms.\n This randomized, double-blind, 24-week, fixed-dose study compared olanzapine (n = 202) and ziprasidone (n = 192) for patients with schizophrenia or schizoaffective disorder and experiencing prominent depressive symptoms. Outcome measures included change in Calgary Depression Scale for Schizophrenia (CDSS) score from baseline to 8 weeks (primary outcome) and changes in CDSS, Montgomery-Asberg Depression Rating Scales, Positive and Negative Syndrome Scale, and Global Assessment of Functioning (GAF) scores for 24 weeks. Statistical analyses included mixed-effects model repeated measures (primary analysis) and change from baseline to last observation carried forward (LOCF).\n At baseline, patients had moderate depressive symptoms (mean Montgomery-Asberg Depression Rating Scales total score, 27.3). For 8 weeks, patients treated with olanzapine or ziprasidone had significant improvements on CDSS. Treatment group differences were not statistically significant (P = 0.493, mixed-effects model repeated measures; P = 0.497, LOCF). For 24 weeks, olanzapine-treated patients showed significantly greater improvements in depressive symptoms (results varied by depression measure and statistical approach) and GAF (P < 0.017, LOCF). A significantly higher proportion of olanzapine-treated patients completed the study (44.6% vs 29.7%; P = 0.003) and remained longer on medication (median, 163 vs 73 days, P < 0.001), compared with ziprasidone-treated patients. Olanzapine-treated patients experienced significantly (P < 0.05) greater increases in triglycerides, HgbA1c, and weight.\n For 24 weeks, olanzapine-treated patients had greater and more sustained participation in treatment, during which time significantly greater improvements were observed in depressive symptoms and GAF scores, along with increases in weight and certain metabolic parameters as compared with ziprasidone-treated patients.", "To compare the relative efficacy and safety of lesopitron 4-80 mg/d versus lorazepam 2-4 mg/d and placebo in a subgroup of patients with anxiety history taken from a larger study of patients with a primary diagnosis of generalized anxiety disorder (GAD).\n Six-week, randomized, double-blind, parallel, placebo and lorazepam-controlled, Phase II, single-center, outpatient study.\n Outpatient clinic.\n One hundred sixty-one patients with GAD were randomized in the main study; 68 with a documented history of GAD or anxiety disorder not otherwise specified were included in the subgroup.\n After a one-week placebo lead-in, patients were randomized to receive placebo, lesopitron, or lorazepam twice daily for six weeks, followed by a one-week taper period. Efficacy was assessed using the Hamilton Rating Scale for Anxiety (HAM-A) and the Clinical Global Impressions scale. Safety was assessed through physical examinations, monitoring of vital signs, 12-lead electrocardiograms, laboratory analyses, and adverse event monitoring.\n An overall mean improvement in the HAM-A total score between baseline and end point for all three treatment groups was seen, with mean changes of 3.4 (95% CI 2.0 to 4.8), 6.1 (95% CI 4.1 to 8.1), and 6.1 (95% CI 4.6 to 7.6) for the placebo, lesopitron, and lorazepam groups, respectively (omnibus p = 0.044, uncorrected). Positive treatment effects were also observed in the subgroup population on several other measures and suggest that additional therapeutic trials may be warranted. Future trials could be stratified on the basis of referral status (symptomatic volunteer vs. clinical patient with preexisting illness) or previous exposure to anxiolytics, and use a fixed-dose rather than flexible-fixed-dose design.\n The subgroup analysis represents a comparison of treatment outcome in GAD patients presenting with a history of previous episodes of GAD or anxiety disorder not otherwise specified compared with those who were experiencing their first episode of GAD and reported no anxiety history. Although the overall study analysis was equivocal, for the approximately 40% of patients with recurrent anxiety disorder, beneficial effects for both lesopitron and lorazepam are suggested.", "Patients suffering from schizophrenic psychoses sometimes insufficiently respond to antipsychotic monotherapy and then combination approaches are preferred. We aimed in validating the add-on of ziprasidone and risperidone to clozapine, and we performed a randomised head-to-head trial. Patients with partial response to clozapine were randomly attributed to augmentation with ziprasidone (n = 12) or risperidone (n = 12). Efficacy assessments included the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Negative Symptoms (SANS), the Hamilton Depression Scale (HAMD), the Clinical Global Impression (CGI) and the Global Assessment of Functioning (GAF). Furthermore, several safety and tolerability measures were obtained. After six weeks, both groups showed significant reductions of positive and negative symptoms. In addition, affective state, psychosocial functioning and clozapine side effects improved without significant differences between the groups. Both approaches were well tolerated. However, the ziprasidone group experienced a small elongation of the QTc interval and a reduction of extrapyramidal symptoms. Patients under clozapine-risperidone therapy developed a rise of serum prolactin levels. The clozapine augmentation with ziprasidone or risperidone resulted in significant psychopathological improvements. The side effects differed between the treatment groups. Further head-to-head comparisons of atypical antipsychotics as add-on to clozapine are necessary.", "Ipsapirone is an azopirone derivative that selectively interacts with serotonin-1A (5-HT1A) receptors and fails to affect other neurotransmitter receptors. In this study, ipsapirone at 15 mg or 30 mg was compared with diazepam at 15 mg and placebo in a double-blind, random assignment study design in patients with generalized anxiety disorder (GAD). During 4 weeks of treatment, both active drugs were therapeutically superior to placebo, without significant drug vs. drug therapeutic differences. The side-effect profile of ipsapirone at 15 mg was favorable compared to diazepam, but at 30 mg ipsapirone produced significant gastrointestinal disturbances.", "Cognitive deficits are a core feature of schizophrenia. As a target of intervention, improvements in cognition may lead to improvements in functional outcome.\n The present paper is the first report, to our knowledge, on the neurocognitive effects of aripiprazole. Unlike other second-generation antipsychotics, aripiprazole is a D(2) and D(3) receptor partial agonist. It is unknown what effects this unusual pharmacological profile may yield on neurocognition.\n The present open-label study included data on 169 patients with schizophrenia or schizoaffective disorder who were randomly treated with aripiprazole or olanzapine. Subjects received a neurocognitive battery at baseline, week 8, and 26.\n The aripiprazole group had a significantly greater dropout rate than the olanzapine group. Neurocognitive data were reduced through a principal components analysis that yielded a three-factor solution. The factors were general cognitive functioning, executive functioning, and verbal learning. For general cognitive functioning, both groups improved from baseline and the effects were relatively stable over the 26-week protocol. There were no differential treatment effects. For executive functioning, neither group improved significantly from baseline. For verbal learning, the aripiprazole group improved significantly from baseline to the 8th and 26th week of assessment, and there was a between-group effect favoring aripiprazole over olanzapine that was largely attributable to the differences in performance within the 8th week. Separate analyses were conducted for a measure of sustained attention (Continuous Performance Test-Identical Pairs). There were no differential treatment effects on this measure.\n The findings from this open-label study suggest that the neurocognitive effects of aripiprazole are at least as good as those of olanzapine.", "Ninety-eight patients with multiple sclerosis (MS) in the chronic progression phase entered a 3-year clinical trial to determine if azathioprine (AZ) alone or with adrenal cortical steroids stabilizes the course of MS. In group AM, the patients took AZ throughout and methylprednisolone (MP) for the first 36 weeks. Group AP received AZ and placebo instead of MP. Group PP took placebos for both drugs. We adjusted the AZ to maintain the total white blood cell count within 3,000 to 4,000/mm3; we gave the MP in a fixed dose \"pulse\" and alternate-day regimen. The \"intent-to-treat\" groups had no statistically significant differences in the rates of progression among the 3 treatments. Subgroup analysis suggests that patients in the AM group who completed treatment exactly according to protocol did statistically significantly better than the placebo recipients using the sum of Standard Neurological Examination scores, slightly better using the quantitative neuro-performance tests, but no better using Mickey's Illness Severity Scores or Kurtzke's Disability Status Scale. Also, the AZ-treated groups had half the relapse rate of the placebo-treated group. Adverse reactions to AZ accounted for most withdrawals. Hematologic and hepatic abnormalities were significantly associated with AZ, but serious non-MS abnormalities were uncommon and were equally distributed among the 3 groups. Addition of MP to the AZ slightly improved the efficacy of the treatment, but also increased the adverse effects. The benefits of AZ with or without steroids did not outweigh the risks, and therefore we do not recommend this treatment for patients with chronic progressive MS.", "Zotepine and thiothixene were compared for clinical efficacy and safety in a double-blind trial. Using overall improvement ratings and Gorham's BPRS, zotepine rated higher improvement in motor retardation, suspiciousness, mannerisms and posturing symptoms, suggesting that it has both activating and antipsychotic activities. Thiothixene produced higher improvement ratings in symptoms such as hallucinatory behavior, somatic concerns, anxiety, guilt feelings, tension, depressive mood and uncooperativeness. As for side effects, there was a significantly lower frequency of dry mouth and insomnia with zotepine when compared with thiothixene. The lower incidence of insomnia is interesting in view of zotepine's clinical activating effects. There were no abnormal laboratory findings.", "Clozapine and risperidone were the first two \"second-generation\" antipsychotic drugs approved for schizophrenia. There is currently little information about their comparative efficacy from head-to-head clinical trials. The purpose of this study was to examine the comparative efficacy of clozapine and risperidone for positive and negative symptoms, depression, parkinsonian side effects, and indexes of neuroendocrine function in schizophrenic patients who met a priori criteria for partial response to traditional neuroleptic agents.\n After a baseline fluphenazine treatment period, 29 patients participated in a 6-week, double-blind, parallel-group comparison of the effects of these agents.\n Clozapine was superior to risperidone for positive symptoms and parkinsonian side effects, but there were no significant differences between the drugs on two measures of negative symptoms, Brief Psychiatric Rating Scale total scores, and depression scores. The clozapine patients, but not the risperidone patients, demonstrated significant reductions from the fluphenazine baseline in positive symptoms, total symptoms, and depression. In addition, clozapine produced fewer effects on plasma prolactin than risperidone or fluphenazine. The mean daily doses during week 6 of the trial were 403.6 mg of clozapine and 5.9 mg of risperidone.\n The findings from this study indicate that these drugs have both important differences and similarities in their comparative efficacy in chronically ill, partially responsive patients with schizophrenia. Further research on second-generation antipsychotic drugs in this patient population that addresses key methodological issues, such as optimal dose and treatment duration, are needed.", "The current study examines whether antidepressants, contrary to current thinking, are safe and effective treatments for generalized anxiety disorder (GAD) not complicated by depression or panic disorder.\n Randomized, double-blind, placebo-controlled, flexible-dose, 8-week treatment study comparing imipramine hydrochloride (mean maximum daily dose, 143 mg), trazodone hydrochloride (255 mg), and diazepam (26 mg).\n Two hundred thirty patients with a DSM-III diagnosis of GAD in whom major depression and panic disorder has been excluded, and who had a Hamilton Anxiety Scale total score of at least 18.\n Seventy-five percent of patients were treated in family practice settings in the community, with the remainder treated in psychiatric practices, either academic or private.\n Patients treated with diazepam showed the most improvement in anxiety ratings during the first 2 weeks of treatment, with somatic symptoms being most responsive. From week 3 through week 8 trazodone achieved comparable, and imipramine somewhat better, anxiolytic efficacy when compared with diazepam, with psychic symptoms of tension, apprehension, and worry being more responsive to the antidepressants. Among completers, moderate to marked improvement was reported by 73% of patients treated with imipramine, 69% of patients treated with trazodone, 66% of patients treated with diazepam, but only 47% of patients treated with placebo. Overall, patients treated with antidepressants reported a higher rate of adverse effects than diazepam-treated patients, but attention rates were the same across all treatments.\n The results of the study need replication, but suggest a potentially important role for antidepressants, particularly imipramine, in patients suffering from GAD.", "Few long-term studies have compared the efficacy and safety of typical and atypical antipsychotic medications directly in patients with a first episode of psychosis who met the criteria for schizophrenia or a related psychotic disorder. This study compared the acute and long-term effectiveness of haloperidol with that of olanzapine in patients with first-episode psychosis in a large, controlled clinical trial.\n Patients with first-episode psychosis (N=263) were randomly assigned under double-blind conditions to receive haloperidol or olanzapine and were followed for up to 104 weeks. Domains measured included psychopathology, psychosocial variables, neurocognitive functioning, and brain morphology and metabolism. This report presents data from clinical measures of treatment response and safety data from the 12-week acute treatment phase.\n Haloperidol and olanzapine were associated with substantial and comparable baseline-to-endpoint reductions in symptom severity, which did not differ significantly in last-observation-carried-forward analyses. However, in a mixed-model analysis, olanzapine-treated subjects had significantly greater decreases in symptom severity as measured by the Positive and Negative Syndrome Scale total score and negative and general scales and by the Montgomery-Asberg Depression Rating Scale but not as measured by the Positive and Negative Syndrome Scale positive scale and by the Clinical Global Impression severity rating. Olanzapine-treated patients experienced a lower rate of treatment-emergent parkinsonism and akathisia but had significantly more weight gain, compared with the haloperidol-treated patients. Overall, significantly more olanzapine-treated subjects than haloperidol-treated subjects completed the 12-week acute phase of the study (67% versus 54%).\n As expected on the basis of previous studies, both olanzapine and haloperidol were effective in the acute reduction of psychopathological symptoms in this group of patients with first-episode psychosis. However, olanzapine had several relative advantages in therapeutic response. Although the nature of adverse events differed between the two agents, retention in the study was greater with olanzapine. Retention in treatment is important in this patient population, given their risk of relapse. Longer-term results are needed to determine whether treatment with atypical antipsychotics results in superior outcomes for a first episode of schizophrenia.", "The treatment of schizophrenic patients who fail to respond to adequate trials of neuroleptic drugs is a major challenge. Clozapine has been one treatment option; however, it is not universally effective and is limited in its use by safety concerns. With the introduction of newer agents, their performance relative to clozapine is of great clinical interest.\n The primary objective of this study was to evaluate the efficacy and safety of olanzapine versus clozapine among treatment resistant DSM-IV schizophrenic patients. The study was primarily designed to demonstrate the \"noninferiority\" of olanzapine compared to clozapine after 18 weeks of double-blind treatment. Conclusions were based on the one-sided lower 95% confidence limit about the treatment effect observed from the primary efficacy variable (Positive and Negative Syndrome Scale [PANSS] Total).\n Mean changes from baseline to end point in PANSS Total score, using a last observation carried forward technique, showed that both agents were comparably effective in neuroleptic resistant patients, i.e., demonstrated the \"noninferiority\" of olanzapine when compared to clozapine. Overall, significantly fewer olanzapine-treated patients (4%) discontinued for an adverse event than their clozapine-treated (14%) counterparts (p =.022). Among spontaneously reported adverse events, increased salivation, constipation, dizziness, and nausea were reported significantly more often among clozapine-treated patients, whereas only dry mouth was reported more often among olanzapine-treated patients.\n Olanzapine was demonstrated to be noninferior to clozapine and better tolerated among resistant schizophrenic patients clinically eligible for treatment with clozapine.", "The authors compared the efficacy and safety of three atypical antipsychotics (clozapine, olanzapine, and risperidone) with one another and with haloperidol in the treatment of patients with chronic schizophrenia or schizoaffective disorder.\n In a double-blind trial, 157 inpatients with a history of suboptimal treatment response were randomly assigned to treatment with clozapine, olanzapine, risperidone, or haloperidol for 14 weeks (an 8-week escalation and fixed-dose period followed by a 6-week variable-dose period).\n Clozapine, risperidone, and olanzapine (but not haloperidol) resulted in statistically significant improvements in total score on the Positive and Negative Syndrome Scale. Improvements seen in total and negative symptom scores with clozapine and olanzapine were superior to haloperidol. The atypical drugs, particularly olanzapine and clozapine, were associated with weight gain.\n The effects of atypical antipsychotics in this population were statistically significant but clinically modest. The overall pattern of results suggests that clozapine and olanzapine have similar general antipsychotic efficacy and that risperidone may be somewhat less effective. Clozapine was the most effective treatment for negative symptoms. However, the differences among treatments were small.", "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.", "40 inpatients suffering from a schizophrenia (ICD-9) were treated with either zotepine or perazin. The study was continued for a period of 28 days. Assessment of clinical efficacy was effected via BPRS, AMDP, CGI and SANS; tolerance was assessed by means of Simpson's scale. In addition, EEG, ECG and laboratory controls were conducted. The overall therapeutic efficacy was good, and it was not possible to distinguish one group from the other, i.e. both substances were equally effective, judged by means of the psychopathometric tools that were at our disposal. In 11 patients of the zotepine group and in 9 patients of the perazin group, slight extrapyramidal symptoms were observed. No clinically relevant changes were seen in EEG, ECG and laboratory controls in both groups." ]	Azapirones appeared to be useful in the treatment of GAD, particularly for those participants who had not been on a benzodiazepine. Azapirones may not be superior to benzodiazepines and do not appear as acceptable as benzodiazepines. Side effects appeared mild and non serious in the azapirone treated group. Longer term studies are needed to show that azapirones are effective in treating GAD, which is a chronic long-term illness.
CD004780	[ "6349737", "14606735", "18515890", "2673479", "3899049", "17999405", "9356557", "9356558" ]	[ "Brief psychotherapy in family practice. A controlled prospective intervention trial.", "A randomized controlled trial of an education and counselling intervention for families after stroke.", "Cognitive--behavioural therapy and family intervention for relapse prevention and symptom reduction in psychosis: randomised controlled trial.", "A trial of family therapy v. a relatives group for schizophrenia.", "A controlled evaluation of inpatient family intervention. I. Preliminary results of the six-month follow-up.", "Randomized clinical trial of a family intervention for prostate cancer patients and their spouses.", "Three-year trials of personal therapy among schizophrenic patients living with or independent of family, I: Description of study and effects on relapse rates.", "Three-year trials of personal therapy among schizophrenic patients living with or independent of family, II: Effects on adjustment of patients." ]	[ "In a prospective (controlled) trial, the result in 18 patients receiving eight, weekly half-hour sessions of brief problem-oriented dynamic psychotherapy was compared with the result in an equal number receiving eight, weekly half-hour sessions of family practitioner therapy and in another 20 receiving no additional therapy. The subjects were drawn from patients at ten suburban family practices in Sydney. They had had psychological complaints for at least six months. No differences between the three treatment groups were found in the final outcome, either in a symptom severity and social dysfunction factor or in a physical disability and medication factor.", "To determine whether education and counselling after stroke leads to improved family functioning and psychosocial outcomes for stroke patients and their spouses, and better functional and social outcomes for patients.\n Two-group randomized controlled trial. Data were collected on admission to and discharge from rehabilitation, and again six months later.\n Rehabilitation units at Repatriation General Hospital and Griffith Hospital, in Adelaide, South Australia.\n Sixty-two stroke patients and their spouses, 32 in the intervention group and 30 in the control group.\n Stroke information package and three visits from a social worker trained in family counselling.\n Family functioning: McMaster Family Assessment Device (FAD); functional status: Barthel Index (BI); social recovery: Adelaide Activities Profile (AAP); depression: Geriatric Depression Scale (GDS); anxiety: Hospital Anxiety and Depression Scale (HADS); mastery: Mastery Scale (MS); health status: SF-36.\n At six months the intervention group had better family functioning for both patients (mean FAD difference 0.19) and spouses (mean difference 0.09). A modest benefit in functional status for intervention patients (mean BI difference 1.3) was related to improved family functioning. Intervention patients reported better social recovery (mean AAP differences: domestic chores 5.7, household maintenance 4.6, social activities 11.5), but there were no significant effects on depression, anxiety, mastery or health status.\n An education and counselling intervention maintained family functioning, and in turn led to improved functional and social patient outcomes. This approach helps patients and their spouses to make the optimal adjustment to living with stroke.", "Family intervention reduces relapse rates in psychosis. Cognitive-behavioural therapy (CBT) improves positive symptoms but effects on relapse rates are not established.\n To test the effectiveness of CBT and family intervention in reducing relapse, and in improving symptoms and functioning in patients who had recently relapsed with non-affective psychosis.\n A multicentre randomised controlled trial (ISRCTN83557988) with two pathways: those without carers were allocated to treatment as usual or CBT plus treatment as usual, those with carers to treatment as usual, CBT plus treatment as usual or family intervention plus treatment as usual. The CBT and family intervention were focused on relapse prevention for 20 sessions over 9 months.\n A total of 301 patients and 83 carers participated. Primary outcome data were available on 96% of the total sample. The CBT and family intervention had no effects on rates of remission and relapse or on days in hospital at 12 or 24 months. For secondary outcomes, CBT showed a beneficial effect on depression at 24 months and there were no effects for family intervention. In people with carers, CBT significantly improved delusional distress and social functioning. Therapy did not change key psychological processes.\n Generic CBT for psychosis is not indicated for routine relapse prevention in people recovering from a recent relapse of psychosis and should currently be reserved for those with distressing medication-unresponsive positive symptoms. Any CBT targeted at this acute population requires development. The lack of effect of family intervention on relapse may be attributable to the low overall relapse rate in those with carers.", "Schizophrenic patients living in high contact with relatives having high expressed emotion (EE) were recruited for a trial of social interventions. The patients were maintained on neuroleptic medication, while their families were randomly assigned to education plus family therapy or education plus a relatives group. Eleven out of 12 families accepted family therapy in the home, whereas only six out of 11 families were compliant with the relatives group. Non-compliance was associated with a poorer outcome for the patients in terms of the relapse rate. The relapse rate over nine months in the family therapy stream was 8%, while that in compliant families in the relatives group stream was 17%. Patients' social functioning showed small, non-significant, gains. The data from the current trial were compared with data from a previous trial. The lowering of the relapse rate in schizophrenia appears to be mediated by reductions in relatives' EE and/or face-to-face contact, and is not explained by better compliance with medication. Reduction in EE and/or contact was associated with a minuscule relapse rate (5%). Very little change occurred in families who were non-compliant with the relatives group. On the basis of these findings, we recommend that the most cost-effective procedure is to establish relatives groups in conjunction with family education and one or more initial family therapy sessions in the home. It is particularly important to offer home visits to families who are unable to or refuse to attend the relatives groups.", "Although family intervention is practiced in most psychiatric hospitals, there are no adequately controlled studies of its efficacy. This study was designed to answer, in part, the following question: What is the relative efficacy of hospitalization with family intervention as compared with hospitalization without family intervention for patients with major psychiatric disorders who are in need of hospital treatment and for whom both treatments are judged clinically feasible? This is our first report, presenting preliminary data on six-month follow-up for the first three quarters of the total sample of 144 patients (80 with schizophrenic disorder and 64 with major affective disorder).", "Few intervention studies have been conducted to help couples manage the effects of prostate cancer and maintain their quality of life. The objective of this study was to determine whether a family-based intervention could improve appraisal variables (appraisal of illness or caregiving, uncertainty, hopelessness), coping resources (coping strategies, self-efficacy, communication), symptom distress, and quality of life in men with prostate cancer and their spouses.\n For this clinical trial, 263 patient-spouse dyads were stratified by research site, phase of illness, and treatment; then, they were randomized to the control group (standard care) or the experimental group (standard care plus a 5-session family intervention). The intervention targeted couples' communication, hope, coping, uncertainty, and symptom management. The final sample consisted of 235 couples: 123 couples in the control group and 112 couples in the experimental group. Data collection occurred at baseline before randomization and at 4 months, 8 months, and 12 months.\n At 4-month follow-up, intervention patients reported less uncertainty and better communication with spouses than control patients, but they reported no other effects. Intervention spouses reported higher quality of life, more self-efficacy, better communication, and less negative appraisal of caregiving, uncertainty, hopelessness, and symptom distress at 4 months compared with controls, and some effects were sustained to 8 months and 12 months.\n Men with prostate cancer and their spouses reported positive outcomes from a family intervention that offered them information and support. Programs of care need to be extended to spouses who likely will experience multiple benefits from intervention.\n 2007 American Cancer Society", "The study of individual psychotherapeutic approaches to the treatment of schizophrenia has yielded equivocal findings, partly because of methodologic problems. Further, the ability of psychosocial treatments to prevent psychotic relapse appears to lessen over time. The authors' goal was to develop and test a demonstrably effective individual therapy for schizophrenia.\n Using a study design that addressed previous methodologic issues, the authors evaluated personal therapy specifically designed to forestall late relapse in patients with schizophrenia. They evaluated the effectiveness of personal therapy over a period of 3 years after hospital discharge among 151 patients with schizophrenia or schizoaffective disorder diagnosed according to Research Diagnostic Criteria. The patients were randomly assigned to receive either personal therapy or contrasting therapies in one of two concurrent trials. One trial studied patients who were living with family (N = 97); the other studied patients who were living independent of family (N = 54).\n All of the patients had extensive psychiatric histories, but only 44 (29%) experienced recurrent psychotic episodes over the 3-year study period, and only 27 (18%) prematurely terminated the study; most of those who left the study were in the no-personal-therapy conditions. Among patients living with family, personal therapy was more effective than family and supportive therapies in preventing psychotic and affective relapse as well as noncompliance. However, among patients living independent of family, those who received personal therapy had significantly more psychotic decompensations than did those who received supportive therapy.\n Personal therapy had a positive effect on adverse outcomes among patients who lived with family. However, personal therapy increased the rate of psychotic relapse for patients living independent of family. The application of personal therapy might best be delayed until patients have achieved symptom and residential stability.", "Previous analyses of the personal and social adjustment of outpatients with schizophrenia have either relied on the assessment of unrepresentative patients who survived without relapse or used analyses that included relapse assessments, a potential confound when different rates of relapse existed among treatment conditions. The authors' goal was to conduct a study of the effects of personal therapy on outcome that was designed to take into consideration the effects of relapse.\n They evaluated the effectiveness of personal therapy over 3 years after hospital discharge among 151 patients with schizophrenia or schizoaffective disorder. The patients were randomly assigned to receive personal therapy or contrasting therapies in one of two concurrent trials. One trial included patients who were living with family (N = 97); the other included patients who were living independent of family (N = 54). Patients were assessed at 6-month intervals over 3 years of treatment on measures of personal and social adjustment; patients who relapsed and restabilized and those who did not relapse were included.\n Personal therapy had positive effects on broad components of social adjustment (role performance) but had few differential effects on symptoms, and patients receiving personal therapy remained more anxious than patients who received family or supportive therapy. For patients who were living with family, personal therapy led to better outcomes in overall performance than did the other treatments. Although family therapy had only one positive effect on patients' social adjustment, the personal adjustment (residual symptoms) of patients who received family therapy appeared to improve more than that of patients receiving personal or supportive therapy. For patients not living with family, personal therapy was more successful than supportive therapy in improving work performance and relationships out of the home. Longitudinal effects of personal therapy on symptoms were similar to those of family and supportive therapies, particularly in the first 2 years, but personal therapy effect sizes increased over time on measures of social adjustment.\n Personal therapy has pervasive effects on the social adjustment of patients with schizophrenia that are independent of relapse prevention. Supportive therapy, with or without family intervention, produces adjustment effects that peak at 12 months after discharge and plateau thereafter. However, personal therapy, a definitive psychosocial intervention, continues to improve the social adjustment of patients in the second and third years after discharge. Brief treatment would appear to be less effective than a long-term, disorder-relevant intervention for schizophrenia." ]	There is some evidence to suggest that family therapy may be effective compared to treatment as usual in the short term. However, this is based on few trials that included only a small number of participants, all of which had issues regarding potential bias. There is insufficient evidence to be able to determine whether family therapy offers any advantage over other types of psychological interventions, or whether one type of family therapy is more effective than another. The field would benefit from a large, well-conducted trial.
CD009073	[ "9431617", "8367786", "19411450", "20023338", "16306834", "10101819", "17665339", "18261963" ]	[ "1997 Volvo Award winner in clinical studies. The effect of pedicle screw instrumentation on functional outcome and fusion rates in posterolateral lumbar spinal fusion: a prospective, randomized clinical study.", "A prospective, randomized study of lumbar fusion. Preliminary results.", "Posterior short-segment fixation with or without fusion for thoracolumbar burst fractures. a five to seven-year prospective randomized study.", "Long segment instrumentation of thoracolumbar burst fracture: fusion versus nonfusion.", "Posterior fixation of thoracolumbar burst fracture: short-segment pedicle fixation versus long-segment instrumentation.", "A randomized prospective study of posterolateral lumbar fusion. Outcomes with and without pedicle screw instrumentation.", "Radiographic analysis of fusion progression following one-level cervical fusion with or without plate fixation.", "Choice of plate may affect outcomes for single versus multilevel ACDF: results of a prospective randomized single-blind trial." ]	[ "A prospective randomized clinical study.\n To evaluate supplementary pedicle screw fixation (Cotrel-Dubousset) in posterolateral lumbar spinal fusion.\n The rationale behind lumbar fusion is to eliminate pathologic motion to relieve pain. To improve fusion rates and to allow reduction, a rigid transpedicular screw fixation may be beneficial, but the positive effect of this may be counter-balanced by an increase in complications.\n The inclusion criteria were severe, chronic low back pain from spondylolisthesis Grades 1 and 2 or from primary or secondary degenerative segmental instability. One hundred thirty patients were randomly allocated to receive no instrumentation (n = 66) or Cotrel-Dubousset instrumentation (n = 64) in posterolateral lumbar fusion. Variables were registered at the time of surgery and at 1 and 2 years after surgery.\n Follow-up was achieved in 97.7% of the patients. Fusion rates deduced from plain radiographs were not significantly different between instrumented and noninstrumented groups. The functional outcome assessed by the Dallas Pain Questionnaire improved significantly in both groups, and there were no significant differences in results between the two groups, except for significantly better (P < 0.06) functional outcome in relation to daily activities in the instrumented group when neural decompression had been performed. The global patients' satisfaction was 82% in the instrumented group versus 74% in the noninstrumented group (not significant). Fixation of instrumentation increased operation time, blood loss, and early reoperation rate significantly. Patients experienced only a few minor postoperative complications; none were major. Two infections appeared in the Cotrel-Dubousset group. Significant symptoms from misplacement of pedicle screws were seen in 4.8% of the instrumented patients.\n Lumbar posterolateral fusion with pedicle screw fixation increases the operation time, blood loss, and reoperation rate, and leads to a significant risk of nerve injury. The functional outcome improves significantly with high patient satisfaction, with or without instrumentation. No significant differences were observed between the two groups in functional outcome and fusion rate. The only gain in functional outcome from instrumentation was found in the daily activity category in patients with supplementary neural decompression. The results of this study do not justify the general use of pedicle screw fixation alone as an adjunct to posterolateral lumbar fusion.", "One hundred, twenty-four patients undergoing lumbar or lumbosacral fusion for degenerative conditions were entered into a prospective study. The patients were randomly assigned to one of three treatment groups. Group I underwent posterolateral fusion using autogenous bone graft. Group II had autogenous posterolateral fusions supplemented by a semi-rigid pedicle screw/plate fixation system (Luque II; Danek Medical, Memphis, Tennessee). Group III patients underwent posterolateral autogenous fusion with a rigid pedicle screw/rod fixation system (Texas Scottish Rite Hospital [TSRH]-Danek Medical, Memphis, Tennessee). All the patients were operated on by the same surgeon, identical bone grafting technique was used in all, and all were treated in an identical fashion postoperatively. Fusion status was determined from the anteroposterior, oblique, and flexion-extension radiographs obtained at 1 year. Clinical results were rated as excellent if the patients were pain-free and had returned to work; good if the patients had mild backache requiring non-narcotic analgesics and had returned to work; fair if continuing back pain prevented a return to work; or poor if the pain was worse than that which the patient experienced preoperatively or the patient required revision surgery. Nine patients who were originally assigned to Group II or Group III were placed in Group I intraoperatively. This change was due to the identification of severe osteopenia and the determination that pedicle screw purchase was poor. One patient was lost to follow-up. Thus, 51 patients were in Group I, 35 in Group II, and 37 in Group III. Follow-up ranged from 9 to 28 months, averaging 16 months.(ABSTRACT TRUNCATED AT 250 WORDS)", "The impact of fusion as a supplement to short-segment instrumentation for the treatment of thoracolumbar burst fractures is unclear. We conducted a controlled clinical trial to define the effect of fusion on lumbar spine and patient-related functional outcomes.\n From 2000 to 2002, seventy-three consecutive patients with a single-level Denis type-B burst fracture involving the thoracolumbar spine and a load-sharing score of <or=6 were managed with posterior pedicle screw instrumentation. The patients were randomly assigned to treatment with posterolateral fusion (fusion group, n = 37) or without posterolateral fusion (nonfusion group, n = 36). The patients were followed for at least five years after surgery and were assessed with regard to clinical and radiographic outcomes. Clinical outcomes were evaluated with use of the Frankel scale, the motor score of the American Spinal Injury Association, a visual analog scale, and the Short Form-36 (SF-36) questionnaire. Radiographic outcomes were assessed on the basis of the local kyphosis angle and loss of kyphosis correction.\n No significant difference in radiographic or clinical outcomes was noted between the patients managed with the two techniques. Both operative time and blood loss were significantly less in the nonfusion group compared with the fusion group (p < 0.05). Twenty-five of the thirty-seven patients in the fusion group still had some degree of donor-site pain at the time of the latest examination.\n Posterolateral bone-grafting is not necessary when a Denis type-B thoracolumbar burst fracture associated with a load-sharing score of <or=6 is treated with short-segment pedicle screw fixation.", "The treatment of thoracolumbar burst fracture is a controversial issue. Although spinal fusion has been a touchstone of spinal fixation, nonfusion technique have become raising its popularity recently. Some studies suggested that nonfusion had several advantages over fusion. The aim of this prospective study was to compare long segment posterior instrumentation with fusion versus long-segment posterior instrumentation without fusion.\n For this purpose, 42 consecutive patients were assigned to two groups. Group 1 included 21 patients treated by long segment instrumentation with fusion (WF), whereas Group 2 included 21 patients treated by long segment instrumentation without fusion (WOF). Long segment instrumentation was hook fixation (claw hooks attached to second upper vertebra and infralaminar hooks attached to first upper vertebra) above and pedicle fixation (pedicle screws attached to first and second lower vertebrae) below the fractured vertebra.\n Measurements of local kyphosis, sagittal index and anterior vertebral height compression showed that both group had similar outcome at final follow-up. Moreover, there was no difference between the two groups according to low back outcome score. Also, implant failure rate (4.7%) was quite low in both groups. However, WF group had prolonged operative time, increased blood loss and donor site morbidity.\n Radiological and clinical parameters demonstrated that spinal fusion is not necessary in long segment posterior instrumentation for the management of thoracolumbar burst fractures.", "The treatment of thoracolumbar burst fracture is a controversial issue. Short-segment (SS) pedicle fixation has become a popular treatment option. However, there are several studies regarding the high rate of failure. The aim of this prospective study was to compare SS versus long-segment (LS) instrumentation.\n For this purpose, 18 consecutive patients were assigned to two groups. Group 1 included nine patients treated by SS pedicle fixation, whereas group 2 included nine patients treated by LS instrumentation. SS instrumentation was pedicle fixation one level above and below the fractured vertebra. LS instrumentation was hook fixation (claw hooks attached to second upper vertebra and infralaminar hooks attached to first upper vertebra) above and pedicle fixation (pedicle screws attached to first and second lower vertebrae) below the fractured vertebra.\n As a result, measurements of local kyphosis, sagittal index, and anterior vertebral height compression showed that the LS group had a better outcome at final follow-up (P < 0.05). Also, the SS group had a 55% failure rate, whereas the LS group had prolonged operative time and increased blood loss. However, there was no difference between the two groups according to Low Back Outcome Score.\n In conclusion, radiographic parameters demonstrated that LS instrumentation is a more effective management of thoracolumbar burst fractures. Nevertheless, clinical outcome was the same between the two groups. However, our conclusions were based on posterior-only surgery. Anterior column support would negate the need for LS fixation. Also, SS would have been more successful if two above and two below pedicle screws were used.", "A prospective evaluation of the clinical and radiographic outcomes of 71 patients who underwent lumbar fusion, with or without transpedicular instrumentation. The patients completed a questionnaire that determined pain relief, medication use, return to work, and overall satisfaction with surgery.\n To explore the effect, if any, of instrumentation on the outcome of lumbar fusion surgery, according to reports of the patients, and whether there is a correlation between the radiographic determination of a solid fusion and the same patient-reported outcome.\n The literature on this topic reports pseudarthrosis rates from 0% to 57% and good to excellent results from 56% to 95%. These studies provide no clear-cut recommendations concerning the effect of added lumbar instrumentation on patient-reported outcome in a prospective manner using concurrent control subjects.\n The patients were randomized to groups with and without instrumentation after deciding to undergo a lumbar fusion and consenting to enter the study. Radiographs were obtained and questionnaires filled out at 6 weeks, 6 months, 1 year, and 2 years after surgery.\n There was no statistical difference in patient-reported outcome between the two groups. There was a slight nonsignificant trend toward increased radiographic fusion rate in the group with instrumentation that did not correlate with an increased patient-reported improvement rate.\n These results do not provide data that indicate a benefit in outcome from added instrumentation in elective lumbar fusions.", "Anterior cervical discectomy and fusion (ACDF) using bone graft or a cage with plate fixation is an accepted technique for the treatment of symptomatic degenerative disc disease. It is, however, debatable whether a plate is really necessary to increase the progress of fusion. Thus, the aim of this randomized and controlled prospective study was to evaluate whether ACDF with a cage and anterior plate fixation results in a greater progress of fusion compared with ACDF using a stand-alone cage.\n 37 candidates for ACDF were treated either with a stand-alone cage (study group) or with a cage+plate fixation (control group). 19 patients were randomized to be stabilized with a stand-alone cage and 18 patients were treated with a cage and additional anterior plate fixation. The progress of cervical fusion over time was compared by radiostereometric analysis (RSA). Follow-up examinations pre- and postoperatively were done using the Visual Analogue Scale (VAS) for neck and arm pain. Radiographic assessment of fusion using an RSA-control was done after one, six and twelve weeks, as well as after six months, and one and two years postoperatively. Mann-Whitney test for unpaired values was used to determine the statistical differences in residual intervertebral motion.\n Three-dimensional analysis of segmental motion (left-right, cranio-caudal, and posterior-anterior) did not reveal any statistical differences between both groups at any examination time postoperatively ( P>0.05). The VAS score did not differ between the groups ( P>0.05).\n Anterior plate fixation did not demonstrate an improvement in the progress of fusion in one-level ACDF.", "Conflicting views exist according to the individual philosophy about various plate designs that can be used in anterior cervical discectomy and fusion (ACDF) to achieve clinical and radiological improvement within shortest time period. No prospective randomized study has ever been conducted to clarify the relationship between clinical outcomes, fusion rates, and the choice of plate (static vs. dynamic design).\n To compare the clinical and radiological outcomes of patients treated with one-level or multiple levels ACDF using cervical plates of dynamic (slotted-holes) versus static (fixed-holes) design.\n Single masked, prospective, randomized study.\n Over a 4-year period, 66 patients (M:F=37:29) had ACDF using either dynamic (n=33) or static (n=33) plates for intractable radiculopathy as the result of degenerative cervical spine disease. Overall, 28 patients had single-level fusion and 38 had two or three levels fused.\n Visual Analogue Pain scores (VASs), Neck Disability Index (NDI), and radiological criteria of established fusion.\n The qualifying subjects were randomized to receive ACDF using either fixed-holes (static) or the slotted-holes (dynamic) anterior cervical plates. Clinical and radiographic data were collected and analyzed. Paired-sample t test was used to correlate clinical and radiological outcomes and General Linear Model Analysis of Variance (GLM ANOVA) with repeated measures was used to detect outcome differences between the two groups for single and multiple fusions.\n At a mean follow-up of 16 months (range, 12-24), 49 patients (73.7%) had clinical success and 56 (85%) showed radiological fusion. Although clinical success was a predictor of fusion (p=.043), the reverse was not true (p=.61). In single-level fusion, no statistical difference of outcome was observed between the two groups but multilevel fusions with dynamic plate showed significantly lower VAS and NDI than those with static plates (p=.050).\n Although clinical improvement is a good predictor of successful ACDF, radiological evidence of fusion alone is not reliable as a parameter of success. The design of plate does not affect the outcomes in single-level fusions but statistics indicate that multiple-level fusions may have better clinical outcome when a dynamic plate design is used." ]	This review included only eight small trials and five different comparisons of methods of pedicle fixation in various participants while looking at a variety of outcomes at different time points. Overall, evidence is insufficient to inform the selection of different methods of pedicle screw fixation or the combined use of fusion. However, in the absence of robust evidence to support fusion, it is important to factor the risk of long-term donor site pain related to bone harvesting into the decision of whether to use this intervention. Further research involving high-quality randomised trials is needed.
CD002039	[ "11096165", "8326334", "2668784", "8709686", "15789920", "19769536", "10755397", "8229026", "8849352" ]	[ "A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis.", "A double blind study on azathioprine efficacy in multiple sclerosis: final report.", "A placebo-controlled, randomized, double-masked, variable dosage, clinical trial of azathioprine with and without methylprednisolone in multiple sclerosis.", "Delta: a randomised double-blind controlled trial comparing combinations of zidovudine plus didanosine or zalcitabine with zidovudine alone in HIV-infected individuals. Delta Coordinating Committee.", "[Assessment of early immunosuppressive therapy in the prevention of complications of Graves' disease].", "Azithromycin plus artesunate versus artemether-lumefantrine for treatment of uncomplicated malaria in Tanzanian children: a randomized, controlled trial.", "Long-term survival of stage I multiple myeloma given chemotherapy just after diagnosis or at progression of the disease: a multicentre randomized study. Cooperative Group of Study and Treatment of Multiple Myeloma.", "A randomised clinical trial comparing prednisone and azathioprine in myasthenia gravis. Results of the second interim analysis. Myasthenia Gravis Clinical Study Group.", "Comparison of azathioprine, methotrexate, and the combination of the two in the treatment of rheumatoid arthritis. A forty-eight-week controlled clinical trial with radiologic outcome assessment." ]	[ "Etanercept, which blocks the action of tumor necrosis factor, reduces disease activity in patients with long-standing rheumatoid arthritis. Its efficacy in reducing disease activity and preventing joint damage in patients with active early rheumatoid arthritis is unknown.\n We treated 632 patients with early rheumatoid arthritis with either twice-weekly subcutaneous etanercept (10 or 25 mg) or weekly oral methotrexate (mean, 19 mg per week) for 12 months. Clinical response was defined as the percent improvement in disease activity according to the criteria of the American College of Rheumatology. Bone erosion and joint-space narrowing were measured radiographically and scored with use of the Sharp scale. On this scale, an increase of 1 point represents one new erosion or minimal narrowing.\n As compared with patients who received methotrexate, patients who received the 25-mg dose of etanercept had a more rapid rate of improvement, with significantly more patients having 20 percent, 50 percent, and 70 percent improvement in disease activity during the first six months (P<0.05). The mean increase in the erosion score during the first 6 months was 0.30 in the group assigned to receive 25 mg of etanercept and 0.68 in the methotrexate group (P= 0.001), and the respective increases during the first 12 months were 0.47 and 1.03 (P=0.002). Among patients who received the 25-mg dose of etanercept, 72 percent had no increase in the erosion score, as compared with 60 percent of patients in the methotrexate group (P=0.007). This group of patients also had fewer adverse events (P=0.02) and fewer infections (P= 0.006) than the group that was treated with methotrexate.\n As compared with oral methotrexate, subcutaneous [corrected] etanercept acted more rapidly to decrease symptoms and slow joint damage in patients with early active rheumatoid arthritis.", "Forty patients, affected by multiple sclerosis with remitting-relapsing or progressive course, were included in a double blind study of treatment with azathioprine (2 mg/kg/day) lasting 3 years. The mean changes on the Expanded Disability Status Scale and in the survival analysis show a trend in favour of azathioprine both in slowing disease progression and reducing relapse frequency. These findings, repeatedly observed in similar trials, indicate that azathioprine should be used in the treatment of multiple sclerosis.", "Ninety-eight patients with multiple sclerosis (MS) in the chronic progression phase entered a 3-year clinical trial to determine if azathioprine (AZ) alone or with adrenal cortical steroids stabilizes the course of MS. In group AM, the patients took AZ throughout and methylprednisolone (MP) for the first 36 weeks. Group AP received AZ and placebo instead of MP. Group PP took placebos for both drugs. We adjusted the AZ to maintain the total white blood cell count within 3,000 to 4,000/mm3; we gave the MP in a fixed dose \"pulse\" and alternate-day regimen. The \"intent-to-treat\" groups had no statistically significant differences in the rates of progression among the 3 treatments. Subgroup analysis suggests that patients in the AM group who completed treatment exactly according to protocol did statistically significantly better than the placebo recipients using the sum of Standard Neurological Examination scores, slightly better using the quantitative neuro-performance tests, but no better using Mickey's Illness Severity Scores or Kurtzke's Disability Status Scale. Also, the AZ-treated groups had half the relapse rate of the placebo-treated group. Adverse reactions to AZ accounted for most withdrawals. Hematologic and hepatic abnormalities were significantly associated with AZ, but serious non-MS abnormalities were uncommon and were equally distributed among the 3 groups. Addition of MP to the AZ slightly improved the efficacy of the treatment, but also increased the adverse effects. The benefits of AZ with or without steroids did not outweigh the risks, and therefore we do not recommend this treatment for patients with chronic progressive MS.", "Because the benefits of zidovudine (AZT) in HIV-infected individuals are small and do not last long the Delta trial was designed to test whether combinations of zidovudine with didanosine (ddl) or zalcitabine (ddC) were more effective than AZT alone in extending survival and delaying disease progression.\n The trial was randomised, double blind, and international. 3207 participants were allocated to either AZT (600 mg per day) alone (1055), AZT plus ddl (400 mg per day) (1080), or AZT plus ddC (2.25 mg per day) (1072). Participants either had symptoms of HIV disease (if AIDS, with a CD4 cell count of > 50 x 10(6)/L) or a CD4 count of less than 350 x 10(6)/L; 2124 had not had zidovudine before (Delta 1) and 1083 had for at least 3 months (Delta 2).\n Over a median follow-up of 30 months, 699 participants died, and 936 of the 2765 without AIDS at entry developed AIDS or died. In participants who had not had AZT before, both combination regimens had substantial benefits in terms of survival (regardless of disease stage at entry); a relative reduction in mortality of 42%, compared to AZT alone (95% Cl 25% to 55%), for AZT plus ddl and of 32% (95% Cl 22% to 47%) for AZT plus ddC. In participants who had had AZT before, the addition of ddl improved survival (p = 0.05; relative reduction 23% [95% Cl 0% to 41%]) but there was no direct evidence of benefit from the addition of ddC (p = 0.47; relative reduction 9% [95% Cl--17% to 29%]). The overall difference in survival between the treatment groups was significant (p < 0.0001; a relative reduction in mortality, compared to AZT alone, of 33% (95% Cl 20% to 44%) for AZT plus ddl and 21% (95% Cl 6% to 34%) for AZT plus ddC). Benefit in terms of disease progression was seen mainly in participants not previously treated with AZT and overall. There was no unexpected toxicity from the combination treatments.\n Initiation of treatment with combinations of AZT plus ddl or ddC prolongs life and delays disease progression compared with AZT alone. The addition of ddl to participants already treated with AZT also improves survival, although the benefit appears less.", "Regardless the autoimmune origin of Graves' disease, the preferred method of its treatment remains antithyroid drug administration. Use of immunosuppressive agents (mostly steroids) is still limited to the therapy of disease complications, such as proliferative ophthalmopathy. The aim of the study was to assess the influence of early immunosuppressive treatment of autoimmune thyrotoxicosis with azathioprine on the course of the disease and the incidence of its complications. The study comprised 64 patients (47 females and 17 males aged 20-43 years) for the first time diagnosed with Graves' disease. The subjects were randomised into two groups. Group I consisted of 28 patients treated only with antithyroid drugs, the remaining 36 subjects additionally receiving azathioprine were included into group II. The dose of both drugs was adjusted during the treatment according to metabolic status of each patients. The treatment was continued for 8-14 months, the follow-up duration after therapy withdrawal was 5 years. Euthyreosis was achieved in all patients 2-8 weeks after treatment initiation. No drug intolerance symptoms were observed in group I. In four patients additionally treated with azathioprine, gastrointestinal side effects or leucopenia were present. The disease relapse was observed during the follow-up period in 15 (53.5%) patients of group I and in 3 (8.3%) of group II, the difference was statistically significant (p<0.01). Only one patient receiving additionally azathioprine presented ophthalmic symptoms compared with seven subjects (25%) treated only with antithyroid drugs (p<0.001). The patients of group I were also more frequently referred to surgical treatment due to rapid goitre growth (accordingly 5 (17.8%) and 1 (2.7%) patients, p=0.07), the difference between both groups not being statistically significant.\n Additional early immunosuppressive treatment significantly decreased frequency of Graves' disease complications and thyrotoxicosis recurrence. The use of azathioprine may be advised in patients with contraindications to the radical Graves' disease treatment and in prophylaxis of its complications.", "Acute febrile illness is the most common cause of outpatient attendance and mortality for children in Africa. Malaria and bacterial disease are difficult to differentiate with limited diagnostic facilities. Combinations of antibiotics and antimalarials are potentially attractive for treatment of the syndrome. Azithromycin plus artesunate (AT+AS) is an effective antimalarial combination for adults in Asia.\n We performed an individually randomized, open-label trial of AZ+AS versus artemether-lumefantrine (AL) involving children (age, 6-59 months) with uncomplicated malaria in Muheza, Tanzania. The primary outcome was parasitological failure by day 28. Parasitological failure by day 42 and failure corrected for reinfection were major secondary outcomes.\n Of 2497 children screened, 261 were eligible; 129 were randomized to the AZ+AS arm, and 132 were randomized to the AL arm; 92% and 91%, respectively, underwent follow-up to 28 days. Planned interim analysis was performed after 200 patients reached day 28 follow-up and led the Data and Safety Monitoring Board to halt further recruitment. All children had a complete initial response to treatment, but 69 (58%) of 119 children in the AZ+AS arm and 24 (20%) of 120 in the AL arm had asexual parasites at or by day 28 (adjusted odds ratio for failure with AZ+AS treatment, 6.1; 95% confidence interval, 3.3-11.4; P < .001). When analysis was restricted to children with recrudescence, the parasitological failure rate was 32% in the AZ+AS arm and 9% in the AL arm. This difference was maintained at day 42.\n This trial does not support the use of AZ+AS as treatment for malaria or acute febrile illness in children in areas of Africa with high levels of existing antimalarial drug resistance.\n ClinicalTrials.gov NCT00694694.", "We conducted a randomized trial to evaluate whether melphalan-prednisone (MPH-P) treatment administered just after diagnosis improves survival of stage I multiple myeloma (MM). Between January 1987 and March 1993, 145 consecutive previously untreated patients with stage I MM were randomized between treatment with MPH-P (administered for 4 days every 6 weeks) just after diagnosis and treatment only at disease progression. Survival was not influenced by MPH-P treatment either administered just after diagnosis or at disease progression (64 vs 71 months respectively). Comparing the first with the second group the odds ratio of death is 1.17 (95% confidence interval 0.57-2.42; P = 0.64). Disease progression occurred within a year in about 50% of patients who were initially untreated. Response rate was similar in both groups, but duration of response was shorter in patients who were treated at disease progression (48 vs 79 months, P = 0.044). Patients actually treated at disease progression (34/70) survived shorter than those who had neither disease progression nor treatment (56 vs > 92 months; P = 0.005). Starting MPH-P just after diagnosis does not improve survival and response rate in stage I MM, with respect to deferring therapy until disease progression. However, patients with stage I MM randomized to have treatment delayed and who actually progressed and were treated had shorter survival than those with stable disease and no treatment. Biologic or other disease features could identify these subgroups of patients.", "From January 1983 to October 1990, 41 patients with generalised myasthenia gravis were randomly given either prednisone or azathioprine. The main goal was to record the time to the occurrence of the first episode of deterioration. During a mean follow-up of 30 months, 21 patients showed deterioration, 12 in the prednisone group and nine in the azathioprine group (p = 0.40). No difference was observed between the two groups in muscular score and functional grade, assessed at the end of each treatment year, or in tolerance. Treatment failure occurred in 17 patients, 12 in the prednisone group and five in the azathioprine group (p = 0.02); even after adjustment for imbalances in prognostic features, the failure rate remained 2.8 times higher in the prednisone group than in the azathioprine group (p = 0.5). In the patients in whom treatment failed, symptoms were initially more severe than in the others, but the combination of prednisone and azathioprine resulted in clinical improvement, consisting of remission or only minor deficits in half of the patients after two years of treatment. These findings indicate that azathioprine increases treatment response compared with prednisone, although no difference in the duration of improvement was demonstrated. Nevertheless, it appears that the most severe forms of the disease, often resistant to prednisone or azathioprine alone, could benefit from the combination of both drugs.", "To assess the relative efficacy of methotrexate (MTX), azathioprine (AZA), and their combination in the treatment of rheumatoid arthritis (RA) in a double-blind, prospective, multicenter, controlled trial.\n Two hundred nine patients with active RA were treated with escalating doses of MTX (5-15 mg/week), AZA (50-150 mg/day), or combination (5mg MTX/week plus 50 mg AZA/day-7.5 mg MTX/week plus 100 mg AZA/day), with opportunity to increase the dosage at 6-week intervals. The patients were evaluated for significant clinical and laboratory improvement and assessed for radiologic progression at 48 weeks.\n One hundred ten patients remained on the initial, randomly assigned therapeutic regimen. The percentage of patients who were responders, defined as those who had 30% or greater improvement in at least 3 of 4 variables, was 38% for the combination treatment, 26% for AZA, and 45% for MTX (P = 0.06). A trend toward decreased radiologic progression was seen in the MTX-treated patients. Termination of treatment due to adverse experience occurred more frequently with combination and AZA treatments than with MTX treatment. Lack of effectiveness, adverse gastrointestinal effects, and liver enzyme elevation were the most frequent causes of treatment discontinuation.\n This study establishes that the combination of MTX and AZA in the dosages utilized is not associated with more toxicity than treatment with single agents; however, enhanced efficacy is also not seen. There is a trend toward decreased radiologic progression in patients treated with MTX." ]	Although immediate use of AZT halved disease progression during the first year, this effect was not sustained, and there was no improvement in survival in the short or long term.
CD001421	[ "18532969", "2677866", "3090849", "15288222", "6384851", "2429687", "15288215", "16192503", "3524550", "11048468" ]	[ "Haemostasis after cold-knife conisation: a randomised prospective trial comparing cerclage suture versus electro-cauterization.", "Hemostasis and cold knife cone biopsy: a prospective randomized trial comparing a suture versus non-suture technique.", "Conization by carbon dioxide laser or cold knife in the treatment of cervical intra-epithelial neoplasia.", "The role and comparison of two techniques of paracervical block for pain relief during suction evacuation for first-trimester pregnancy termination.", "Use of an antifibrinolytic agent (tranexamic acid) and lateral sutures with laser conization of the cervix.", "A randomized trial of Citanest with Octapressin for relief of pain associated with laser vaporization of the cervix.", "A randomized comparison of sublingual and vaginal misoprostol for cervical priming before suction termination of first-trimester pregnancy.", "Hepatic resection by the Cavitron Ultrasonic Surgical Aspirator increases the incidence and severity of venous air embolism.", "Preoperative cervical dilatation: a trial of laminaria tents and prostaglandin F2 alpha gel.", "Postoperative bleeding after coronary revascularization. Comparison between tranexamic acid and epsilon-aminocaproic acid." ]	[ "The purpose of this study was to compare two different techniques of obtaining haemostasis after cold-knife conisation.\n Seventy-eight women who required conisation for treatment of cervical intraepithelial neoplasia were prospectively enrolled in a randomised clinical trial to receive either cerclage with cold-knife conisation or cautery with cold-knife conisation. Outcome measures evaluated include estimated blood loss, operative time, early late haemorrhage and dysmenorrhoea. The short- and long-term morbidity was compared, and a six-month follow up was completed.\n The procedure-related complication rate was 16.7% in the cautery group, compared with 7.0% in the suture group (P < 0.05). The cerclage group had significantly shorter operative time and intraoperative blood loss than the cautery group (P < 0.05). Postoperative bleeding and dysmenorrhoea were observed in eight (10.2%), and 14 cases (17.9%), in cerclage and cautery group, respectively. Three cases (3.8%) had postoperative infections and were cured with oral antibiotics.\n These results suggest that cerclage suturing technique provided excellent haemostasis and restoration of normal cervical anatomy. Cerclage suture of the cone bed is superior to only cauterization as a method of achieving haemostasis, with significantly less blood loss and shorter operative time.", "Two methods of obtaining hemostasis after cold knife cone biopsy were compared in a prospective randomized trial involving 200 patients. One method relied primarily on hemostatic sutures, and the other involved the use of a styptic solution (Monsel's solution) and vaginal pack, thus avoiding the use of sutures altogether. The short- and long-term morbidity in these two groups were compared and 12-month follow-up was completed. The use of sutures did not reduce the incidence of primary hemorrhage. Secondary hemorrhage was twice as frequent in the suture group, although this trend did not quite reach statistical significance. During long-term follow-up, significantly more patients in the suture group developed menstrual symptoms, cervical stenosis, and unsatisfactory colposcopy, requiring further operative intervention as a result.", "In a randomized trial concerning 123 women with CIN, 59 were treated with laser conization under colposcope without further hemostatic remedy and 64 with cold knife conization guided by Schiller's iodine dyeing supported by side sutures, vaginal packing and postoperative oral administration of tranexam acid. Follow-up with colposcopy and cytology was done 3 and 12 weeks post-conization and then every 6 months. The average follow-up period was 36 months (28-48). Peroperative bleeding was rather less pronounced in the laser group. Postoperatively, however, bleeding requiring treatment was significantly less common in the laser group (5%) than in the cold knife group (17%). The recurrence rate of CIN was 7% in the laser group and 10% in the knife group. Stenosis of the cervical canal developed in 7% of the patients in the laser group and in 3.5% in the knife group. After 12 weeks the squamocolumnar junction was visible in its full extent in 66% of the laser treated patients compared with 38% of the cold knife treated patients. It is concluded that laser conization is a safe procedure even without hemostatic procedures other than the coagulation abilities of the laser beam itself, as used in this work.", "This prospective study assessed the role and compared two techniques of paracervical block (PCB) for pain relief during suction evacuation for first-trimester termination of pregnancy following cervical priming with misoprostol. One-hundred and thirty-five women undergoing suction evacuation up to 12 weeks of gestation were randomized into three groups: (a) 5 mL of 1% lignocaine injected at the 4 and 8 o'clock positions of the vaginal vault; (b) 5 mL of 1% lignocaine injected at the 4 and 8 o'clock positions of the cervix and (c) no PCB. Pain scores during PCB, cervical dilatation and during and after suction evacuation were compared among the three groups. The sedation and satisfaction levels were also compared. There were no statistically significant differences in the pain levels during PCB, cervical dilatation and suction evacuation and in the satisfaction levels among the three groups. Patients with a lighter sedation level experienced more pain. In conclusion, PCB did not improve the pain levels during first-trimester suction termination of pregnancy after cervical priming with misoprostol and use of intravenous sedation, regardless of whether the local anaesthetic was injected into the cervix or the vaginal vault.", "One hundred forty patients who underwent laser conization and 220 patients who underwent laser miniconizations were prospectively randomized into two study groups. One treatment group was given antifibrinolytic therapy in the form of tranexamic acid (Cyklokapron, KabiVitrum, Sweden) intraoperatively and for 14 days postoperatively. The other group did not receive antifibrinolytic therapy. In the group of 68 patients with laser conizations who were given antifibrinolytic therapy, no postoperative hemorrhages occurred, whereas there were eight such hemorrhages in 72 conizations (11%) in the untreated patients. This difference is statistically significant (P = .004, Fisher exact test for two proportions). Also, for laser miniconization, the frequency of postoperative hemorrhage was almost halved, from 9.1% in 110 patients not receiving antifibrinolytic therapy to 5.5% in the 110 treated patients. The use of lateral cervical sutures did not reduce the frequency of postoperative hemorrhage at laser conization in the present study.", "Fifty women undergoing laser vaporization of the cervix for cervical intraepithelial neoplasia were randomly allocated to one of two groups. In one group the patients received no anaesthesia, in the other the ectocervix was infiltrated with 2 ml of Citanest with Octapressin (prilocaine 3% with 0.03 i.u./ml. of felypressin) immediately before the procedure. The pain experienced by each group was assessed immediately after treatment by visual analogue and verbal rating scales. The pain experienced by those women receiving local anaesthesia was significantly reduced as assessed by the visual analogue scale (P = 0.011) and this reduction was not quite significant by the verbal rating scale (P = 0.06). The Citanest group had less troublesome bleeding but the difference in bleeding between the two groups was not significant.", "This randomized trial compares the efficacy and side effects of sublingual and vaginal misoprostol for cervical priming before first-trimester pregnancy termination. One-hundred pregnant women between 6 and 12 weeks of gestation opting for termination of pregnancy by suction evacuation were included in this study. The women were randomly allocated into two groups. Group 1 received 400 microg of sublingual misoprostol and group 2 received 400 microg of vaginal misoprostol 2 h prior to suction evacuation. The abortion was carried out by suction evacuation using a Karman's cannula attached to an electrically operated suction machine under intravenous analgesia. Baseline cervical dilatation, duration of the procedure, operative blood loss, side effects and complications were noted in both groups. There was a significant difference between the sublingual and vaginal misoprostol groups with respect to mean cervical dilatation (8.6 mm vs. 6.8 mm, p < 0.05). However, the duration of the procedure (3.03 min vs. 3.16 min) and the amount of blood loss (29 mL vs. 31.2 mL) were not significantly different between the two groups. The women in the sublingual group experienced significantly more shivering and preoperative vaginal bleeding (68% vs. 56%, p < 0.05). None of the women in the two groups had either uterine perforation or excessive hemorrhage. In our study, sublingual misoprostol (400 microg) was significantly more effective in facilitating cervical dilation prior to surgical abortion than vaginal misoprostol.", "The Cavitron Ultrasonic Surgical Aspirator (CUSA) is an innovative tool for resecting hepatic parenchyma, which reduces intraoperative blood loss and perioperative morbidity. We designed this study to compare the incidence and severity of venous air embolism (VAE) detected via transesophageal echocardiography (TEE) during hepatic resection by using either the clamp-crushing method or the CUSA method. Fifty patients scheduled for hepatic resection were randomly assigned to receive hepatic resection by the clamp-crushing method (CC group) or by CUSA (CUSA group). After the induction of anesthesia, the TEE probe was inserted into the patient's esophagus. An independent anesthesiologist graded VAE shown in the 4-chamber view of TEE. All patients in the CUSA group showed VAE during hepatic resection and 44% of the patients had air embolism filling more than half the right heart diameter. In CC group, 68% of the patients showed VAE, which filled less than half the right heart diameter. There were no significant differences in hemodynamics and end-tidal CO2 partial pressure between the two groups. In conclusion, hepatic resection by CUSA increases the incidence and severity of VAE.\n This study demonstrated that venous air embolism during hepatic resection was more frequent and severe when using the Cavitron Ultrasonic Surgical Aspirator. Although we found no evidence of hemodynamic compromise, increased venous air embolism may increase the risk of paradoxical embolism in patients with liver cirrhosis.", "Surgical damage to the cervix in patients undergoing termination of pregnancy may be responsible for serious complications in subsequent pregnancies. Sixty nulliparous women undergoing first trimester termination of pregnancy were randomly allocated to 3 treatment groups, one using laminaria tents preoperatively, one using intracervical PGF2 alpha gel preoperatively and one using no pretreatment. Results showed clear benefits in the laminaria group, in terms of achieving preoperative cervical dilatation and ease of further operative dilatation. Laminaria tents were superior to PGF2 alpha gel which was, in turn, superior to no pretreatment. There were no differences in blood loss or postoperative complications among the 3 groups. Laminaria tents provide a cheap, effective and safe method of reducing the risk of cervical damage in women undergoing surgical termination of pregnancy.", "Microvascular bleeding after Cardiopulmonary bypass (CPB) is mainly due to consumption of clotting factors, platelets damage, and hyperfibrinolysis. Aprotinin, the only antifibrinolytic drug effective in preserving platelets, is no longer available; an alternative regimen based on pure antifibrinolytic drugs has been proposed, since hyperfibrinolysis is known to contribute both to clot lysis and platelet dysfunction. In this study the efficacy of two antifibrinolytic drugs, Tranexamic acid (TA) and epsilon-aminocaproic acid (EACA), was tested in patients undergoing cardiopulmonary bypass (CPB), for primary myocardial revascularization.\n Forty-eight consecutive patients were randomized to receive prophylactically equipotent doses of EACA (group A) or TA (Group B). Platelet count, prothrombin time, fibrin digestion products, blood loss and transfusion requirements recorded after 6 and 24 hours from the end of surgery were compared.\n The two groups were comparable for length of CPB and numbers of grafts; no significant difference was observed in the coagulation parameters considered. Blood losses were less in group B (TA) than in group A (EACA), both at 6 and 24 hours after surgery; homologous blood transfused was also less in group B, but no difference was statistically significant. No adverse effect was observed.\n In coronary patients, TA and EACA exhibit the same effects on blood loss and requirements after CPB; either drug can be safely used in cardiac surgery." ]	Bleeding associated with surgery of the cervix appears to be reduced by vasopressin, used in combination with local anaesthetic. Tranexamic acid appears to be beneficial after knife and laser cone biopsy. There are insufficient data to assess the effects on primary haemorrhage. There is some evidence that haemostatic suturing has an adverse effect on blood loss, cervical stenosis and satisfactory colposcopy.
CD004444	[ "8202971", "3902480" ]	[ "Ganglioside GM1 in acute ischemic stroke. The SASS Trial.", "Effects of GM1 ganglioside in cerebrovascular diseases: a double-blind trial in 40 cases." ]	[ "We sought to assess the safety and efficacy of ganglioside GM1 in acute (< or = 48 hours), anterior circulation ischemic stroke.\n We screened more than 5000 patients at 13 centers in a randomized, double-blind, placebo-controlled, parallel-treatment, clinical trial and enrolled 287 patients. They received 100 mg GM1 or placebo intramuscularly daily for 28 days and were evaluated regularly for 84 days. Number of deaths, the Toronto Stroke Scale, and the Barthel Index were primary outcomes; improvements on the Fugl-Meyer Scale and on a neuropsychological battery were secondary outcomes.\n The groups were balanced for severity, side of stroke, age, sex, race, years of schooling, prior illness, and depression scores. Analyzable data were available on 275 patients; 217 patients completed the trial. Protocol-specified primary and secondary outcome measures showed no significant difference between treatment arms. However, improvement from baseline in the motor component of the Toronto Stroke Scale favored the GM1-treated group at day 28 when GM1 treatment stopped (P = .020); at day 84, the difference still favored the GM1-treated group (P = .057). All 10 components of the Barthel Index, the Fugl-Meyer Scale, and four of the five tests in the neuropsychological battery also favored the GM1 group. Adverse experiences were similar in the two groups.\n GM1 is safe. However, since only certain post hoc tests showed statistically significant differences or trends favoring GM1, another clinical trial is needed to demonstrate efficacy.", "A randomized, double-blind trial on the effects of GM1 ganglioside in cerebrovascular diseases was done on 40 patients; the treatment (40 mg/day i.m. injection) began after the acute phase and lasted 6 weeks. 18 cases took the drug and 16 the placebo. The evaluation of the cases was made by graduating the severity of the clinical signs, and some neurophysiological and morphological parameters, i.e., EEGs, flash-evoked potentials and computer tomography scans. We found that the drug, in comparison with the placebo treatment, improved the clinical signs and also the neurophysiological parameters, whereas it was ineffective for the morphological damage. These data seem of some interest in relation to the action of GM1 ganglioside in the processes of neurotransmission and neuronal plasticity as described in the experimental animal." ]	The evidence available does not support the use of ganglioside treatment to reduce the death rate in SCI patients. No evidence has yet emerged that ganglioside treatment improves recovery or quality of life in survivors.
CD003044	[ "3892073", "3539709", "7016484", "2195106", "15122774", "19730107", "3301614", "20452184", "10528419", "2654285", "3125077", "3315932", "18467909", "15179608", "11515632", "3142949", "3932509", "3319453", "17964789", "17189085", "3282895", "4079669", "3295020" ]	[ "Disease-specific amino acid infusion (F080) in hepatic encephalopathy: a prospective, randomized, double-blind, controlled trial.", "Use of branched chain amino acids for treating hepatic encephalopathy: clinical experiences.", "Comparison between neomycin and lactulose in 173 patients with hepatic encephalopathy: a randomized clinical study.", "Branched chain enriched amino acid versus glucose treatment of hepatic encephalopathy. A double-blind study of 65 patients with cirrhosis.", "Synbiotic modulation of gut flora: effect on minimal hepatic encephalopathy in patients with cirrhosis.", "Bifidobacterium combined with fructo-oligosaccharide versus lactulose in the treatment of patients with hepatic encephalopathy.", "Acidifying enemas (lactitol and lactose) vs. nonacidifying enemas (tap water) to treat acute portal-systemic encephalopathy: a double-blind, randomized clinical trial.", "Probiotics for patients with compensated liver cirrhosis: a double-blind placebo-controlled study.", "[Non-insulin-dependent diabetes mellitus associated with nonalcoholic liver cirrhosis: an evaluation of treatment with the intestinal alpha-glucosidase inhibitor acarbose].", "Lactitol and lactulose for the treatment of subclinical hepatic encephalopathy in cirrhotic patients. A randomised, cross-over study.", "Enterococcus lactic acid bacteria strain SF68 and lactulose in hepatic encephalopathy: a controlled study.", "Lactitol vs. lactulose in the treatment of acute hepatic encephalopathy in cirrhotic patients: a double-blind, randomized trial.", "An open-label randomized controlled trial of lactulose and probiotics in the treatment of minimal hepatic encephalopathy.", "Clostridium difficile pilot study: effects of probiotic supplementation on the incidence of C. difficile diarrhoea.", "Flumazenil in the treatment of acute hepatic encephalopathy in cirrhotic patients: a double blind randomized placebo controlled study.", "A randomized controlled study of peripheral parenteral nutrition in moderate and severe alcoholic hepatitis.", "Controlled trial of nutritional supplementation, with and without branched chain amino acid enrichment, in treatment of acute alcoholic hepatitis.", "Lactitol, a second-generation disaccharide for treatment of chronic portal-systemic encephalopathy. A double-blind, crossover, randomized clinical trial.", "Role of antiparasitic therapy for seizures and resolution of lesions in neurocysticercosis patients: an 8 year randomised study.", "Clinical evaluation of a new starter formula for infants containing live Bifidobacterium longum BL999 and prebiotics.", "Effectiveness of acarbose, an alpha-glucosidase inhibitor, in uncontrolled non-obese non-insulin dependent diabetes.", "Treatment of acute hepatic encephalopathy in cirrhotics with a branched-chain amino acids enriched versus a conventional amino acids mixture. A controlled study of 70 patients.", "Lactitol versus lactulose in the treatment of chronic hepatic encephalopathy. A double-blind, randomised, cross-over study." ]	[ "Seventy-five patients with acute hepatic decompensation superimposed on chronic alcoholic cirrhosis were prospectively randomized for a blinded trial of the treatment of hepatic encephalopathy. The control group received 4 g of enteral neomycin daily along with 25% dextrose by a central venous catheter. The experimental group received a placebo resembling neomycin and isocaloric dextrose plus a modified amino acid mixture enriched with branched-chain amino acids to 36% and deficient in aromatic amino acids and methionine. Thirty patients in the F080 group and 29 in the control group completed the trial. The group receiving the modified amino acid mixture demonstrated a statistically significant improvement in encephalopathy as compared to the neomycin group, while maintaining nitrogen equilibrium. Survival and discharge from the hospital were statistically greater in the group treated with the modified amino acid solution and hypertonic dextrose. Treatment of hepatic encephalopathy in the presence of hepatic decompensation with an amino acid solution formulated for its treatment seems to produce faster, more complete recovery with improved capacity for nutritional support.", "The efficacy of branched chain amino acids in two consecutive clinical studies in patients with severe hepatic encephalopathy was tested. In the preliminary uncontrolled study 19 patients with grade 3-4 hepatic encephalopathy were given an intravenous solution containing leucine 11 g/l, isoleucine 9 g/l, and valine 8.4 g/l in 20% dextrose. A complete recovery of mental state was obtained in all patients in a mean time of 20.5 hours. In a subsequent controlled study 40 patients with grade 3-4 hepatic encephalopathy were randomly assigned to receive intravenous branched chain amino acid in 20% dextrose (group A) or oral lactulose (group B). Twelve patients (70.6%) in group A and eight (47%) in group B regained consciousness in a mean time of 27.6 and 31.5 hours, respectively. The difference in the recovery rate between the two groups, although evident, was not significant. Intravenous branched chain amino acids are thus at least as effective as lactulose in reversing hepatic coma. These data argue strongly in favour of a therapeutic effect of branched chain amino acids in the treatment of hepatic encephalopathy in patients with chronic liver failure.", "A randomized study was performed in order to compare the course of hepatic encephalopathy in patients treated with neomycin plus magnesium sulfate or with lactulose. Admission criteria were: morphological diagnosis of cirrhosis and absence of comorbidity, of contraindications to drugs, or of previous treatments which could influence the outcome. The treatment groups were similar in terms of clinical characteristics, fatalities, recovery rate from grade 1 encephalopathy, and disappearance rate of neuropsychiatric signs. Transitions from severe to grade 1 or 0 encephalopathy showed a 0.17 (NS) difference in favor of neomycin. Early therapy and evidence of precipitating factors showed a favorable prognostic significance. Ascites, hyperbilirubinemia, poor nutritional state, and hypoprothrombinemia showed bad prognostic significance. This is the first large-scale investigation on hepatic encephalopathy. It demonstrated a similar effectiveness of the two drugs in grade 1 encephalopathy and provides a basis for drug selection in the current management of the syndrome.", "We studied the effects of infusion of a branched chain enriched amino acid mixture versus glucose on acute hepatic encephalopathy in patients with cirrhosis. Sixty-five patients were randomly treated with 1 g/kg per day of an amino acid mixture with 40% branched chain contents (32 patients), or isocaloric glucose (33 patients) for a maximum of 16 days. The regimens further included glucose infusion to a total of 26.5 kcal/kg per day and lactulose. The patients took part in the study for 5-6 days. In each group 17 patients woke up. In the amino acid group eleven died and four developed renal failure. In the glucose group ten died, three developed renal and two respiratory failure, and one remained encephalopathic. The coma score worsened in three of the patients who died in the amino acid group, but in all patients who died in the glucose group. The negative nitrogen balance on entry reversed in the amino acid group, but not in the glucose group. Thus, the branched chain enriched amino acid supplement did not change the prognosis for wake-up, but had other effects on the cerebral state and on nitrogen homeostasis.", "Minimal hepatic encephalopathy (MHE) is an important disorder that may seriously impair daily functioning and quality of life in patients with cirrhosis. Treatment with lactulose is of benefit. The possible role of synbiotics (probiotics and fermentable fiber) has not been assessed. We screened 97 consecutive cirrhotic patients without overt hepatic encephalopathy for MHE using the number connection test and measurement of brainstem auditory evoked potentials. MHE, defined by abnormality on at least one test modality, was present in 58 (60%) patients. Fifty-five of these patients with MHE were randomized to receive a synbiotic preparation (n = 20), fermentable fiber alone (n = 20), or placebo (n = 15) for 30 days. Cirrhotic patients with MHE were found to have substantial derangements in the gut microecology, with significant fecal overgrowth of potentially pathogenic Escherichia coli and Staphylococcal species. Synbiotic treatment significantly increased the fecal content of non-urease-producing Lactobacillus species at the expense of these other bacterial species. Such modulation of the gut flora was associated with a significant reduction in blood ammonia levels and reversal of MHE in 50% of patients. Synbiotic treatment was also associated with a significant reduction in endotoxemia. The Child-Turcotte-Pugh functional class improved in nearly 50% of cases. Treatment with fermentable fiber alone was also of benefit in a substantial proportion of patients. In conclusion, treatment with synbiotics or fermentable fiber is an alternative to lactulose for the management of MHE in patients with cirrhosis.", "Hepatic encephalopathy (HE) is a reversible neuropsychiatric syndrome in patients with liver disease. It was suggested that Bifidobacterium+fructo-oligosaccharides (FOS) may decrease blood and brain ammonia levels.\n The study was conducted to compare the efficacy of Bifidobacterium+FOS and lactulose in patients with HE.\n One hundred and twenty-five patients (35 hepatitis B virus infected, 70 hepatitis C virus infected and 20 cryptogenetic cirrhosis) were enrolled in the study. Patients were randomized either to a treatment for 60 days with Bifidobacterium and FOS (group A) or into-group receiving lactulose (group B) in double-blind.\n After 30 days of the study period, the Bifidobacterium+FOS-treated patients compared with lactulose-treated patients showed a significant decrease of Trail Making Test B (TMT B) (P<0.005), and a significant increase of Symbol Digit Modalities Test (P<0.001) and Block Design Test (P<0.001).After 60 days of the study period, the Bifidobacterium+FOS-treated patients compared with lactulose-treated patients showed a significant decrease of NH4 fasting HE1 (P<0.001), TMT A (P<0.05), TMT B (P<0.001), and a significant increase of Symbol Digit Modalities Test (P<0.001) and Block Design Test (P<0.001).\n The treatment with Bifidobacterium+FOS is an alternative to the use of lactulose in patients with cirrhosis, for its usefulness in reducing blood ammonia levels and improvement of psychometric tests.", "A double-blind, controlled trial to study the efficacy of acidifying enemas of lactitol, a new galactoside-sorbitol disaccharide, and lactose vs. nonacidifying tap-water enemas was performed in 45 episodes of acute portal-systemic encephalopathy. At the time of randomization, all patients had encephalopathy of at least Grade 2+ severity, delay in the performance of number connection tests and hyperammonemia. A sequential analysis was performed which revealed after the inclusion of the first 20 patients, a significant failure of the nonacidifying enemas as compared to the lactitol enemas (p less than 0.004). The tap-water enema group was, therefore, suspended but the rest of the study continued after rerandomization for lactose and lactitol groups. A favorable response to treatment was obtained in 19 (86%) of the patients receiving lactitol enemas and in 14 (78%) of those receiving lactose enemas. A similar significant improvement in portal-systemic encephalopathy parameters and index was observed after both treatments. Both types of acidifying enemas induced a significant pH decrease in stool (p less than 0.05). These data suggest that acidifying agents like lactose and lactitol are effective and superior to tap-water enemas for the treatment of acute nitrogenous portal-systemic encephalopathy.", "Gut flora is related to the major complications of liver cirrhosis including hepatic encephalopathy, spontaneous bacterial peritonitis, and variceal bleeding. Prior studies have reported a beneficial effect of gut flora modification with probiotic bacteria in patients with minimal hepatic encephalopathy. We aimed to study the effect of probiotics on clinical and laboratory parameters of patients with compensated cirrhosis.\n A double-blind placebo-controlled study that included patients with liver cirrhosis and at least one major complication of cirrhosis in the past, clinical evidence of portal hypertension, or decreased hepatic synthetic function. Participants were randomly assigned to receive probiotic capsules containing Lactobacillus acidophilus, Lactobacillus bulgaricus, Bifidobacterium lactis, and Streptococcus thermophiles or placebo for a period of 6 mo.\n A total of 36 patients were available for final analysis (distributed equally between the probiotic and placebo groups). The administration of probiotics was not associated with significant differences in either clinical or laboratory parameters between the two groups. Because the lack of a beneficial effect may be related to the compensated liver disease of patients, we conducted a subanalysis of patients with baseline ammonia levels > 50 mmol/L. In this subgroup, the administration of probiotics appeared to significantly reduce the ammonia levels starting after 1 mo of treatment. However, this effect diminished and lost its significance following comparison to the placebo group.\n Our study did not show a significant beneficial effect of probiotic supplementation in patients with compensated liver cirrhosis. Nevertheless, it points toward a possible positive effect of probiotics in patients with above normal baseline ammonia levels. This issue requires further investigation in larger cohorts.\n Copyright Â© 2011 Elsevier Inc. All rights reserved.", "Non-insulin-dependent diabetes mellitus not responding to diet only in patients with non-alcoholic liver cirrhosis is characterized by high post-prandial hyperglycemia. The aim of this study was to evaluate the safety and efficacy of 24 weeks of treatment with 300 mg acarbose per day in 76 consecutive outpatients affected by type 2 diabetes and well-compensated liver cirrhosis. The study design was double-blind cross-over vs placebo. All patients tolerated both treatments well, and no significant variations in liver function tests were observed (< 5% vs pre-treatment). A significant reduction of several parameters was observed only after acarbose: fasting glycemia (19 +/- 6 vs 2 +/- 0.5%; p < 0.01), post-prandial glycemia (41 +/- 9 vs 3 +/- 0.6%; p < 0.01), mean glycemia (30 +/- 8 vs 14 +/- 5%; p < 0.01), daily glycemic variation (52 +/- 8 vs 8 +/- 1%; p < 0.01), HbA1c (16 +/- 1 vs 2 +/- 0.5; p < 0.05), incremental area of C-peptide after a standard meal (80 +/- 19 vs 200 +/- 36 ng/mL/300 min; p < 0.01). After acarbose a significant increase of intestinal voiding/week (98 vs 28%; p < 0.01) and a parallel reduction of blood ammonia levels (52 +/- 9 vs 9 +/- 5%; p < 0.01) were observed. Results clearly document the good tolerability and the absence of toxic effects of acarbose on the liver, due to a theoretic absence of both absorption by the gut and hepatic metabolism of the drug. In fact, acarbose increases peristaltic movement of the gut, stimulates the proliferation of saccharolytic bacteria and simultaneously reduces proteolytic bacterial proliferation, thus actively reducing blood ammonia levels. These unexpected effects of acarbose may be used to advantage for the treatment of type 2 diabetes mellitus in patients with well-compensated liver cirrhosis.", "Fourteen patients with cirrhosis and subclinical hepatic encephalopathy were randomised to treatment with lactitol or lactulose for a 2-month period during which they were monitored clinically, by electroencephalography and by manually administered and computer-based psychometric testing. Following a washout period of 4-6 weeks patients were crossed-over to treatment with the alternative sugar for a similar period of monitoring. None of the patients showed evidence of overt hepatic encephalopathy and only one showed slowing of the electroencephalogram mean cycle frequency at the onset of the trial. However, significant impairment was observed in the group as a whole in the performance of all three manually administered psychometric tests and in four of the ten computer-based test variables. No changes were observed in clinical status or in electroencephalogram mean cycle frequency during treatment with either lactitol or lactulose. However, psychometric performance improved consistently, and to the same degree, during treatment with both sugars. Patients required a mean of 26 g (range 8-36) of lactitol and 25 ml (10-60) of lactulose to achieve two semi-soft stools per day. The majority of patients complained of flatulence during treatment with both sugars but this tended to resolve with continued treatment. Diarrhoea developed in a small number of patients during both treatment periods but this was invariably dose-related. Patients were equally divided in their preference for the two sugars. Patients with subclinical hepatic encephalopathy benefit from treatment with lactitol and lactulose in terms of their psychometric performance. The feasibility and benefits of long-term treatment for this condition need to be elucidated.", "Forty cirrhotic patients with non-advanced hepatic encephalopathy were randomly allocated into groups which were given orally either two capsules three times daily of a preparation of Enterococcus lactic acid bacteria strain SF68 or 30 ml lactulose four times daily. The patients were evaluated over a 10-day course of treatment and for 10 days post-treatment. The Enterococcus SF68 preparation proved to be as effective as lactulose in lowering blood ammonia, and in improving mental state and psychometric performance. Moreover, the effects of Enterococcus SF68, contrary to that of lactulose, persisted longer after treatment withdrawal. Some patients reported diarrhoea and abdominal pain with lactulose. Lactulose is a standard therapy in the treatment of patients with hepatic encephalopathy. In this study, however, the use of the Enterococcus SF68 preparation was shown to offer advantages over lactulose in these patients.", "Lactitol (beta-galactosido-sorbitol) is a nonabsorbable disaccharide available as a powder which, in open comparison, is as effective as lactulose in the treatment of chronic hepatic encephalopathy, but is better tolerated. Twenty-five cirrhotic patients experiencing 28 episodes of acute hepatic encephalopathy were randomized blindly to treatment with either lactitol (n = 15) or lactulose (n = 13). The sugars were dispensed in solutions identical in appearance, taste and pH and of similar osmolarity, which contained either 66.7 gm per 100 ml lactitol or 66.7 ml (44.5 gm) per 100 ml lactulose syrup. The initial dose of 0.75 ml per kg was adjusted to produce two semisoft stools per day. Patients were assessed every 12 hr for 5 days. There were no significant differences in sex ratio, age, body weight, clinical status, duration and extent of coma, etiology of liver disease or of hepatic encephalopathy between the two groups of patients on entry to the trial. An adequate catharsis was obtained with an equivalent mean (+/- 1 S.D.) daily dose of 26 +/- 5 gm lactitol or 31 +/- 7 ml (21 +/- 5 gm) lactulose syrup. During the trial, significant improvements occurred in clinical status and psychometric performance and in the electroencephalogram mean cycle frequencies in the majority of patients in both groups. At the end of the trial, 67% of the patients in the lactitol group and 69% of the lactulose group were clinically normal. However, patients treated with lactitol responded significantly more quickly than patients treated with lactulose.(ABSTRACT TRUNCATED AT 250 WORDS)", "Minimal hepatic encephalopathy (MHE) is associated with poor quality of life and increased work disability. Treatment with lactulose and probiotics has shown some benefit. We compared lactulose with probiotics and a combination of lactulose plus probiotics in the treatment of MHE.\n One hundred and ninety cirrhotic patients without overt encephalopathy [Child's A grade 71 patients (37.4%), Child's B grade 72 patients (37.9%), Child's C grade 47 patients (24.7%)] were evaluated by psychometry (number connection tests A and B or figure connection tests A and B) and P300 auditory event-related potential (P300ERP). MHE was diagnosed by abnormal psychometry and/or P300ERP. Patients were randomized to receive lactulose [group A (n=35): dose 30-60 ml/day], probiotics [group B (n=35): dose 1 capsule three times/day, each capsule contained Streptococcus faecalis 60 million, Clostridium butyricum 4 million, Bacillus mesentricus 2 million, lactic acid bacillus 100 million] and lactulose plus probiotics [group C (n=35)] for 1 month. Response was defined by normalization of the abnormal test parameters.\n MHE was diagnosed in 105 (55.2%) patients. Of the 105 patients, 75 (71%) had both abnormal psychometry and P300ERP, whereas 90 (86%) had abnormal psychometry alone, and 89 patients (85%) had abnormal P300ERP alone. Significant improvement was seen in abnormal psychometry tests (group A: n=31 vs. n=12, group B: n=29 vs. n=14, group C: n=30 vs. n=10), P300ERP (group A: 376.8+/-22.3 vs. 344.3+/-30.6 ms, group B: 385.4+/-28.5 vs. 355.5+/-27.9 ms, group C: 387.7+/-27.5 vs. 347.7+/-31.5 ms) and venous ammonia levels (group A: 102.3+/-63.1 vs. 69.3+/-33.3 micromol/l, group B: 108.2+/-37.5 vs. 75.7+/-33.0 micromol/l, group C: 96.3+/-27.7 vs. 68.7+/-28.4 micromol/l) in lactulose, probiotics and a combination of lactulose plus probiotics groups after treatment. Normalization of abnormal psychometry and P300ERP was seen in 54.8, 51.6 and 56.6% of patients treated with lactulose, probiotics and lactulose plus probiotics groups, respectively.\n A total of 55% of the patients with cirrhosis had MHE. Lactulose or probiotics or combinations of both are equally effective in the treatment of MHE.", "Colonic infection with Clostridium difficile, leading to pseudomembranous colitis, is a common complication of antibiotic therapy, especially in elderly patients. It has been suggested that non-pathogenic probiotic bacteria might prevent the development and recurrence of C. difficile infection. This double-blind, placebo-controlled study examines the role of probiotic administration in the prevention of C. difficile-associated diarrhoea (CDAD) in elderly patients receiving antibiotic therapy. Consecutive patients (150) receiving antibiotic therapy were randomised to receive either a probiotic containing both Lactobacillus and Bifidobacterium or placebo for 20 days. Upon admission to hospital, bowel habit was recorded and a faecal sample taken. Trial probiotic or placebo was taken within 72 h of prescription of antibiotics, and a second stool sample was taken in the event of development of diarrhoea during hospitalisation or after discharge. Of the randomised patients, 138 completed the study, 69 with probiotics in conjunction with antibiotics and 69 with antibiotics alone. On the basis of development of diarrhoea, the incidence of samples positive for C. difficile-associated toxins was 2.9% in the probiotic group compared with 7.25% in the placebo-control group. When samples from all patients were tested (rather than just those developing diarrhoea) 46% of probiotic patients were toxin-positive compared with 78% of the placebo group.", "The aim of this study was to evaluate the effects of flumazenil on hepatic encephalopathy in patients with liver cirrhosis.\n . In the double blind randomized, placebo controlled study, 54 patients with hepatic encephalopathy grade III-IV were randomly assigned to receive either flumazenil 2 mg iv (group A) or placebo (group B); conventional treatment with branched-chain amino acid, saline, glucose, and lactulose was administered in both groups. A 24-hour observation period was established. Clinical improvement was defined as a 3 point decrease in the Glasgow coma score at any time within 24 hours.\n Clinical improvement was obtained in 22/28 patients in group A and in 14/26 in group B (p<0.05); improvement was observed within the first six hours in 21/22 patients in group A and only in 3/14 in group B. Mortality rate was not different between group A and B; however, all 6 non-responders in group A and only 5 out of 12 in group B died within 24 hours. Among patients with post-bleeding encephalopathy, 11 out of 17 in group A and only 2 out of 14 in group B improved (p<0.001).\n Flumazenil may exert a beneficial effect in a subset of patients with acute hepatic encephalopathy; encephalopathy associated with bleeding is more likely to respond to flumazenil; responders to the treatment usually improve within the first 6 hours while lack of response usually represents a bad prognostic sign.", "We performed a controlled trial of peripheral hyperalimentation in moderate and severe alcoholic hepatitis to determine whether improvement in survival and liver function could be obtained. Twelve patients with moderate and 22 with severe alcoholic hepatitis were randomized to 28 days of peripheral parenteral nutrition (PPN) or standard therapy (ST). In the moderate group, six were treated with each therapy. In the severe group, 10 were treated with PPN and 12 with ST. Routine liver tests, hepatocyte function (galactose elimination capacity), estimated hepatic blood flow (galactose clearance) and assessment of ascites and encephalopathy were performed at randomization and at 28 days. Groups were equally matched at randomization. In the moderate group PPN produced no improvement in morbidity (liver tests) and mortality (no deaths). In the severe group there were seven deaths (4 PPN, 3 ST). PPN produced greater improvement than ST in serum bilirubin and transferrin concentrations and a trend toward greater improvement in prothrombin time, serum albumin and galactose elimination capacity. PPN had no deleterious effect on encephalopathy or ascites as only ST patients developed ascites or encephalopathy after randomization. We conclude that PPN compared to ST (1) provides no benefit in moderate alcoholic hepatitis, but (2) did more rapidly improve morbidity (liver tests) and probably liver function in severe alcoholic hepatitis; (3) PPN did not improve early mortality, and (4) it had no deleterious effect on encephalopathy or ascites.", "Sixty-four patients admitted with acute alcoholic hepatitis, with or without underlying cirrhosis, were randomized regardless of encephalopathy to receive a controlled diet either alone, or supplemented orally, nasogastrically, or intravenously as necessary, with 2000 kCal and 10 g nitrogen daily. Whether this came from a conventional protein source or a branched chain amino acid enriched formulation was also randomly determined. In the absence of renal failure, nitrogen intakes of 10 g or more daily were invariably associated with positive nitrogen balance, but complications of liver dysfunction prevented the attainment of significantly more positive balance in the supplemented groups than in controls. Neither in the series as a whole, nor in any identifiable subgroup of patients, was mortality affected by treatment. Changes in prothrombin time and in measured nutritional parameters during the study did not differ between supplemented and control groups, and the observed changes in midarm muscle circumference appeared to reflect changes in degree of fluid retention. Neither enteral nor parenteral branched chain amino acids showed any consistent effect upon encephalopathy.", "A double-blind crossover trial was performed to test the therapeutic usefulness and safety of lactitol, a beta-galactoside sorbitol, against lactose in 18 patients with chronic portal-systemic encephalopathy (PSE). The study included four periods: two for washout and two for lactitol and lactose administration. During washout periods, which lasted two weeks each, patients were stabilized with neomycin plus milk of magnesia. Lactitol and lactose were administered during four weeks each. Ten patients were randomly assigned to receive lactose (group A) and eight patients to receive lactitol (group B) first. PSE parameters, ie, mental state, number connection test performance, asterixis and blood ammonia levels were assessed fortnightly. Electroencephalographic tracings and stool pHs were evaluated at the end of each study period. After the first administration of lactose and lactitol, no statistically significant differences in PSE parameters were found. At the same stage, a significant stool acidification (P less than 0.05) was detected. It is concluded that lactitol seems to be safe and efficacious in treating patients with chronic PSE.", "Neurocysticercosis is a common cause of acquired seizure disorder in developing countries, including India. The role of antiparasitic (albendazole) therapy for seizure control and resolution of lesions is still controversial due to a lack of adequately controlled studies. The objective of the present study was to evaluate the role of albendazole therapy for neurocysticercosis patients with two or more lesions to achieve seizure-free status and resolution of lesions. This was a randomised controlled study in which patients suffering from neurocysticercosis were prospectively followed up for more than 5 years (from January 1997 to January 2005). Patients were divided into two groups: patients in group A (n=150) were treated with a combination of tapered doses of dexamethasone and albendazole, plus antiepileptic drugs; patients in group B (n=150) were treated with antiepileptic drugs plus a placebo control. Patients were followed up every month for the first 6 months and then at 3-month intervals thereafter up to 5 years. Variables of interest were (i) recurrence of seizures; (ii) encephalopathy (headache/vomiting/altered sensorium); (iii) need for subsequent hospital admission; (iv) death; (v) resolution of lesions on follow-up CT. During the first 6 months and at intervals thereafter, increased seizure frequency and hospital readmissions, and increased incidence of encephalopathy were observed in group A (p=0.01), and two patients in this group died with intractable seizures and encephalopathy. A greater proportion of lesions completely resolved in group B (p=0.05), whereas a greater proportion of lesions calcified in group A (p=0.05). Albendazole plus antiepileptic drugs did not have greater beneficial effects than antiepileptic drugs alone, but may have an adverse effect with respect to seizure control, encephalopathy, recurrent hospital admissions, calcification of lesions and cost of treatment.", "The larger number of bifidobacteria in the intestine of breast-fed infants has been associated with their better health compared with formula-fed infants. We assessed the safety and tolerability of an experimental formula containing 2 x 10(7) colony-forming units of Bifidobacterium longum BL999 and 4 g/L of a prebiotic mixture containing 90% galacto-oligosaccharides and 10% fructo-oligosaccharides.\n A 7-mo prospective, randomized, reference-controlled, double-blinded trial was performed in infants who were not breast fed after the 14th day of birth. One hundred thirty-eight infants were enrolled and assigned to receive the control or experimental formula until they were 112 d old. Mean weight gain (primary outcome) and recumbent length, head circumference, tolerability (gastrointestinal symptoms), and overall morbidity (secondary outcomes) were measured at 14, 28, 56, 84, and 112 d of age.\n Equivalence in mean weight gain between the two groups was shown. The treatment difference in the intention-to-treat and per-protocol populations were within the predefined equivalence boundaries of +/-3.9 g/d. No statistically significant difference in recumbent length, head circumference, or incidence of adverse events was found between the two groups. Infants in the experimental group had fewer incidences of constipation and had stool characteristics that suggest that the experimental formula was tolerated well. Furthermore, these infants showed a trend toward fewer respiratory tract infections.\n The starter formula containing BL999 and galacto-oligosaccharides/fructo-oligosaccharides is safe and well-tolerated.", "The effect of acarbose, an alpha-glucosidase inhibitor, on glycaemic control, was compared with placebo in a double-blind, randomised, group comparison study during 16 weeks in 20 non-obese non-insulin dependent diabetic patients in whom sulphonylurea treatment had been withdrawn. There was significant deterioration in glycaemic control as assessed by HbA1 following withdrawal of the sulphonylurea. There was no significant improvement in HbA1 between weeks 0 and 16 in either the acarbose (11.3% and 12.4% respectively) or the placebo group (10.6% and 12.2% respectively). In both the acarbose and placebo treated groups fasting glucose and insulin concentrations were unaltered. This study also suggests that acarbose was not an effective substitute for sulphonylureas in non-obese Type 2 diabetes uncontrolled by diet alone.", "Acute hepatic encephalopathy in 70 cirrhotic patients was monitored during parenteral administration of amino acids between January 1979 and January 1984. The diagnosis of cirrhosis was confirmed by needle biopsy, and HE by conventional clinical and EEG parameters. The infusion of AA solutions was initiated 48 h after admission and during a 5-day period: 34 patients received a control aminoacid solution, a commercially available AA mixture (Azonutril), and 36 patients a modified solution enriched in BAA prepared from crystallized AA dissolved in distilled water. The calorie intake for both groups was 1600 calories per day from glucose and lipid emulsion. No significant difference was noted based on clinical evolution, even though the plasma AAA/BAA ratio was corrected using the modified AA solution. Of the 34 patients in Group 1: 10 improved, 14 were unchanged, 10 deteriorated and 7 died. Of the 36 patients in Group 2: 12 improved, 14 were unchanged, 10 deteriorated and 7 died. EEG tracing evolved in parallel fashion. The authors conclude that modified AA solutions are ineffective in the treatment of acute hepatic encephalopathy in cirrhotic patients.", "Lactitol is a disaccharide analogue of lactulose which is available as a pure crystalline powder. The efficacy of lactitol in the treatment of chronic hepatic encephalopathy was assessed in 9 cirrhotic patients in a randomised, double-blind, cross-over comparison with lactulose. The sugars were dispensed in solutions, identical in taste and appearance and with similar physico-chemical properties, which contained either 66.7 g/100 ml of lactitol or 66.7 ml (44.5 g)/100 ml of lactulose syrup. Patients were treated for periods of 3 months with each sugar, during which time they were monitored frequently by use of a number of clinical, psychometric and laboratory variables. The sugar solutions were dispensed in an initial dose of 0.75 ml/kg which was adjusted, as necessary, in order to produce two semi-soft stools per day. An adequate catharsis was achieved with a mean (+/- 1 SD) equivalent daily dose of 31.9 +/- 11.2 g of lactitol or 32.9 +/- 16.7 ml (21.9 +/- 11.1 g) of lactulose syrup. Both sugars were equally as effective in the treatment of this condition, even though events likely to cause decompensation arose in 5 patients during treatment with lactitol but in only 1 during treatment with lactulose. Side effects appeared to be more frequent during treatment with lactulose, despite the fact that the parent sugar was diluted in the trial solution; thus 5 patients experienced excessive flatulence and 8 experienced diarrhoea on lactulose compared with only 2 and 4 on lactitol, respectively. In all cases the excessive flatulence occurred independently of sugar dosage whereas the development of diarrhoea was dose-related.(ABSTRACT TRUNCATED AT 250 WORDS)" ]	This systematic review questions the beneficial effects of nonabsorbable disaccharides and highlights that there is insufficient high-quality evidence to support this treatment. We found that antibiotics appeared to be superior to nonabsorbable disaccharides in improving hepatic encephalopathy, but it is unclear whether this difference in treatment effect is clinically important to patients. Nonabsorbable disaccharides should not serve as comparator in randomised trials on hepatic encephalopathy.
CD001392	[ "10464834", "786665", "11786454", "10337455", "15741443", "10227321", "6384419", "15562142" ]	[ "Inhaled antibiotic therapy in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa.", "A controlled trial of intermittent oral acetylcysteine in the long-term treatment of chronic bronchitis.", "Reducing antibiotic use for acute bronchitis in primary care: blinded, randomised controlled trial of patient information leaflet.", "Efficacy and tolerability of myrtol standardized in long-term treatment of chronic bronchitis. A double-blind, placebo-controlled study. Study Group Investigators.", "Inhaled fluticasone in bronchiectasis: a 12 month study.", "Decreasing antibiotic use in ambulatory practice: impact of a multidimensional intervention on the treatment of uncomplicated acute bronchitis in adults.", "A randomized, controlled trial of doxycycline in the treatment of acute bronchitis.", "Inhaled tobramycin in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection with Pseudomonas aeruginosa." ]	[ "The aim of this study was to investigate the long-term effectiveness and safety of inhaled antibiotic treatment in non-cystic fibrosis patients with bronchiectasis and chronic infection by Pseudomonas aeruginosa, after standard endovenous and oral therapy for long-term control of the infection had failed. After completing a 2-week endovenous antibiotic treatment to stabilize respiratory status, 17 patients were randomly allocated to a 12-month treatment either with inhaled ceftazidime and tobramycin (group A) or a symptomatic treatment (group B). One patient from group A abandoned inhaled treatment because of bronchospasm and another from group B died before the end of the study. The remaining 15 patients, seven from group A and eight from group B, completed the study. Both groups had similar previous characteristics. The number of admissions and days of admission (mean +/- SEM) of group A [0.6 (1.5) and 13.1 (34.8)] were lower than those of group B [2.5 (2.1) and 57.9 (41.8)] (P < 0.05). Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), PAO2 and PACO2 were similar in the two groups at the end of follow-up, showing a comparable decline in these parameters. There were no significant differences either in the use of oral antibiotics or in the frequency of emergence of antibiotic-resistant bacteria between groups. Microbiological studies suggested that several patients had different Pseudomonas aeruginosa strains. None of the patients presented impaired renal or auditory function at the end of the study. This study suggests that long-term inhaled antibiotic therapy may be safe and lessen disease severity in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa which do not respond satisfactorily to antibiotics administered via other routes.", "In 69 out-patients with chronic bronchitis in 6 centres the effects of acetylcysteine 600 mg daily, 3 days a week for 6 months, and a placebo have been compared in a double-blind controlled trial. Thirty-five patients were treated with the mucolytic and 34 with the dummy preparation. In the former the clinical course of the chronic bronchitis improved to a greater extent and a significantly lower number of exacerbations was observed. The advantages of long-term oral treatment with the mucolytic in chronic bronchitis suggest that it may be useful as an alternative to long-term antibiotic prophylaxis, or to complement brief courses of antibiotics, in addition to the usual physiotherapy.", "To assess whether sharing the uncertainty of the value of antibiotics for acute bronchitis in the form of written and verbal advice affects the likelihood of patients taking antibiotics.\n Nested, single blind, randomised controlled trial.\n Three suburban general practices in Nottingham Participants: 259 previously well adults presenting with acute bronchitis.\n In group A, 212 patients were judged by their general practitioner not to need antibiotics that day but were given a prescription to use if they got worse and standard verbal reassurance. Half of them (106) were also given an information leaflet. All patients in group B (47) were judged to need antibiotics and were given a prescription and encouraged to use it.\n Antibiotic use in the next two weeks. Reconsultation for the same symptoms in the next month.\n In group A fewer patients who received the information leaflet took antibiotics compared with those who did not receive the leaflet (49 v 63, risk ratio 0.76, 95% confidence interval 0.59 to 0.97, P=0.04). Numbers reconsulting were similar (11 v 14). In group B, 44 patients took the antibiotics.\n Most previously well adults with acute bronchitis were judged not to need antibiotics. Reassuring these patients and sharing the uncertainty about prescribing in a information leaflet supported by verbal advice is a safe strategy and reduces antibiotic use.", "This multicenter, placebo-controlled, double-blind, randomized parallel-group trial was conducted to investigate the efficacy and tolerability of myrtol standardized (MYS, Gelomyrtol forte, 3 x 300 mg) in the long-term treatment of patients with chronic bronchitis during the winter. 246 patients received the investigational treatments (MYS: 122, placebo: 124) for at least 1 month; 215 subjects (110 under MYS and 105 under placebo) were evaluable in terms of efficacy (exacerbation rate, the need for antibiotics, symptom scores and general well-being) for the protocol-defined 6 months of treatment. Statistically significantly (p < 0.01) more patients remained without acute exacerbation in the myrtol standardized group (72%) compared to the placebo group (53%). In the placebo group, there was an evident peak in the incidence of exacerbations during the third month of treatment, which was not observed in the active treatment group. In the MYS group, 51.6% of the patients with an acute exacerbation required antibiotics vs. 61.2% under placebo. 62.5% of the patients treated with antibiotics in the MYS group required them for < or = 7 days, whereas 76.7% of the patients in the placebo group treated with antibiotics for exacerbation needed antibiotics for > 7 days. Well-being (assessed in terms of general health and health impairment by cough and expectoration) was significantly better under treatment with MYS. The overall therapeutic efficacy evaluation scored higher for MYS. Therefore, it is concluded that long-term treatment with MYS is equally well tolerated as placebo but is clearly superior in efficacy in terms of protecting against acute exacerbations in patients with chronic bronchitis: it reduces the frequency and intensity of acute exacerbations, the need of antibiotics for them and the health impairment by cough and expectoration.", "The clinical efficacy of inhaled corticosteroid (ICS) treatment has not been evaluated in bronchiectasis, despite the presence of chronic airway inflammation.\n After three consecutive weekly visits, 86 patients were randomised to receive either fluticasone 500 mug twice daily (n = 43, 23F, mean (SD) age 57.7 (14.4) years) or matched placebo (n = 43, 34F, 59.2 (14.2) years) and reviewed regularly for 52 weeks in a double blind fashion.\n 35 and 38 patients in the fluticasone and placebo groups completed the study. Significantly more patients on ICS than on placebo showed improvement in 24 hour sputum volume (OR 2.5, 95% CI 1.1 to 6.0, p = 0.03) but not in exacerbation frequency, forced expiratory volume in 1 second, forced vital capacity, or sputum purulence score. Significantly more patients with Pseudomonas aeruginosa infection receiving fluticasone showed improvement in 24 hour sputum volume (OR 13.5, 95% CI 1.8 to 100.2, p = 0.03) and exacerbation frequency (OR 13.3, 95% CI 1.8 to 100.2, p = 0.01) than those given placebo. Logistic regression models revealed a significantly better response in sputum volume with fluticasone treatment than with placebo among subgroups of patients with 24 hour sputum volume <30 ml (p = 0.04), exacerbation frequency </=2/year (p = 0.04), and sputum purulence score >5 (p = 0.03).\n ICS treatment is beneficial to patients with bronchiectasis, particularly those with P. aerurginosa infection.", "The emergence and spread of antibiotic-resistant Streptococcus pneumoniae in US communities is due, in part, to the excessive use of antibiotics for acute respiratory tract infections.\n To decrease total antibiotic use for uncomplicated acute bronchitis in adults.\n Prospective, nonrandomized controlled trial, including baseline (November 1996-February 1997) and study (November 1997-February 1998) periods.\n Four selected primary care practices belonging to a group-model health maintenance organization in the Denver, Colo, metropolitan area.\n Consecutive adults diagnosed as having uncomplicated acute bronchitis. A total of 2462 adults were included at baseline and 2027 adults were included in the study. Clinicians included 56 physicians, 28 physician assistants or nurse practitioners, and 9 registered nurses.\n The full intervention site received household and office-based patient educational materials, as well as a clinician intervention consisting of education, practice-profiling, and academic detailing. A limited intervention site received only office-based educational materials, and control sites provided usual care.\n Antibiotic prescriptions for uncomplicated acute bronchitis during baseline and study periods.\n Antibiotic prescription rates for uncomplicated acute bronchitis were similar at all 4 sites during the baseline period. During the study period, there was a substantial decline in antibiotic prescription rates at the full intervention site (from 74% to 48% [P = .003]), but not at the control and limited intervention sites (78% to 76% [P = .81] and 82% to 77% [P = .68], respectively). Compared with control sites, changes in nonantibiotic prescriptions (inhaled bronchodilators, cough suppressants, and analgesics) were not significantly different for intervention sites. Return office visits (within 30 days of the incident visit) for bronchitis or pneumonia did not change significantly for any of the sites.\n Antibiotic treatment of adults diagnosed as having uncomplicated acute bronchitis can be safely reduced using a combination of patient and clinician interventions.", "Acute bronchitis is a common reason for visits to primary care physicians and a commonly given reason for antibiotic treatment. However, evidence regarding the efficacy of antibiotics for this syndrome is lacking. In a randomized trial, a one-week course of a frequently used antibiotic, doxycycline, was compared with one week of placebo in 74 otherwise healthy adults with acute bronchitis. The doxycycline group fared no better than the placebo group for all 13 outcomes measured, including duration of cough, clinical improvement at one week, return visits for unresolved symptoms, days away from work, and subjective ratings of cough severity, sleep loss, diminished activity and overall well-being. Doxycycline is not beneficial in the treatment of acute bronchitis in otherwise healthy adults.", "Non-cystic fibrosis (CF) patients with bronchiectasis usually develop chronic bronchial infection with Pseudomonas aeruginosa (PA) that is related to worsening lung function and increased morbidity and mortality.\n To determine whether direct aerosol delivery of tobramycin to the lower airways may control infection and produce only low systemic toxicity.\n A double-blind, placebo-controlled crossover trial involving 30 patients was conducted to determine the clinical effectiveness and safety of 6-month tobramycin inhalation therapy. Patients received 300 mg of aerosolized tobramycin or placebo twice daily in 2 cycles, each for 6 months, with a one-month washout period. The number of exacerbations, number of hospital admissions, number of hospital admission days, antibiotic use, pulmonary function, quality of life, tobramycin toxicity, density of PA in sputum, emergence of bacterial resistance, and emergence of other opportunistic bacteria were recorded.\n The number of admissions and days of admission (mean +/- SD) during the tobramycin period (0.15 +/- 0.37 and 2.05 +/- 5.03) were lower than those during the placebo period (0.75 +/-1.16 and 12.65 +/- 21.8) (p < 0.047). A decrease in PA density in sputum was associated with tobramycin administration in the analysis of the first 6-month cycle (p = 0.038). No significant differences were observed in the number of exacerbations, antibiotic use, pulmonary function, and quality of life. The emergence of bacterial resistance and other bacteria did not differ between the 2 periods of study. Inhaled tobramycin was associated with bronchospasm in 3 patients, but not with detectable ototoxicity or nephrotoxicity.\n Aerosol administration of high-dose tobramycin in non-CF bronchiectatic patients for endobronchial infection with PA appears to be safe and decreases the risk of hospitalization and PA density in sputum. Nevertheless, pulmonary function and quality of life are not improved, and the risk of bronchospasm is appreciable." ]	The evidence available shows a small benefit for the use of prolonged antibiotics in the treatment of bronchiectasis. This review is limited by the diversity of the trials. Further randomised controlled trials with adequate power and standardised end points are required.
CD003562	[ "16566619", "12397048", "12760589" ]	[ "Efficacy and safety of sildenafil in men with serotonergic antidepressant-associated erectile dysfunction: results from a randomized, double-blind, placebo-controlled trial.", "Efficacy of oral sildenafil in hemodialysis patients with erectile dysfunction.", "The efficacy and tolerability of sildenafil in patients with moderate-to-severe pulmonary hypertension." ]	[ "To evaluate the efficacy of short-term treatment with sildenafil citrate in men with serotonin reuptake inhibitor (SRI)-associated erectile dysfunction (ED).\n Men (aged>or=18 years) with major depressive disorder (MDD; DSM-IV criteria) in remission and taking SRIs who experienced SRI-associated ED were enrolled in this multicenter, 6-week, randomized, flexible-dose, double-blind, placebo-controlled trial. The primary study measures were questions 3 (Q3: frequency of penetration) and 4 (Q4: frequency of maintained erections after penetration) of the International Index of Erectile Function (IIEF) questionnaire. Secondary study measures were all other questions and domains of the IIEF, the Erectile Dysfunction Index of Treatment Satisfaction (EDITS), a global efficacy questionnaire (GEQ), and a patient-maintained event log of sexual activity.\n Patients receiving sildenafil (N=71) versus placebo (N=71) reported significantly higher mean+/-SE scores on Q3 (3.9+/-0.2 vs. 3.1+/-0.2, p=.003) and Q4 (3.7+/-0.2 vs. 2.8+/-0.2, p<.001) of the IIEF and significantly higher scores on all domains of the IIEF. Patients receiving sildenafil also reported significantly improved scores on all questions of the EDITS questionnaire (p<.02) and the GEQ (p<.0001) and an increased number of successful sexual intercourse attempts per week (p<.0001) compared with patients receiving placebo. All patients remained in MDD remission (score<or=10 on the Hamilton Rating Scale for Depression). Adverse events in patients taking sildenafil (vs. placebo) were headache (9% vs. 9%), dyspepsia (9% vs. 1%), anxiety (6% vs. 4%), and abnormal vision (3% vs. 0%).\n Short-term (6-week) administration of sildenafil was well tolerated and significantly improved erectile function and overall sexual satisfaction in men with ED associated with SRI therapy for MDD. Sildenafil may be successfully used to treat SRI-associated ED without interruption of antidepressant therapy.", "The aim of this study was to evaluate the efficacy and safety of oral sildenafil to treat erectile dysfunction (ED) in chronic renal failure in patients on hemodialysis (HD). A double-blind, randomized, placebo-controlled study of oral sildenafil (50 mg) administered as required in HD patients with ED was designed. Patients on HD for at least 6 mo and who had a stable relationship with a female sexual partner were included. Patients older than 70 yr with penile anatomic abnormalities, cirrhosis, diabetes, angina, severe anemia, and those who were on nitrate treatment or with a recent history of stroke or myocardial infarction were not included. The International Index of Erectile Dysfunction (IIEF) was employed to evaluate ED and treatment response. Forty-one patients were evaluated (21 received placebo, and 20 sildenafil). Baseline clinical and demographic parameters were similar in both groups. Sildenafil was associated with improvement in the score of all questions and domains of the IIEF, except those related to sexual desire. Using the erectile function domain to evaluate primary efficacy, improvement was observed in 85% of the sildenafil patients compared with 9.5% of placebo patients. Sildenafil use resulted in normal EF scores in 35% of sildenafil patients. Sildenafil was well tolerated. Headaches and flushing occurred in both groups. Dyspepsia was reported by two patients in the sildenafil group. In conclusion, oral sildenafil seems to be an effective and safe treatment for ED in selected patients with chronic renal failure on hemodialysis.", "Pulmonary arterial hypertension is a life-threatening disease for which continuous intravenous infusion of prostacyclin has proved effective. However, it carries the risk of serious complications arising from the complex delivery system. Prostacyclin analogs, endothelin antagonists, and the phosphodiesterase-5 inhibitor sildenafil are emerging promising therapies. This study was aimed at evaluating the utility of oral sildenafil in patients with pulmonary hypertension of varied etiology, poorly controlled on conventional treatment.\n Ten consecutive patients with pulmonary hypertension, either primary or related to previous left-to-right shunts, thromboembolism, or interstitial lung disease, poorly controlled on conventional therapy such as warfarin, calcium antagonists, digitalis, and diuretics, were included. A thorough clinical, laboratory, and comprehensive echo Doppler evaluation was performed before enrollment in the trial to establish the diagnosis and obtain baseline data. Subjects received sildenafil 25 mg 8 hourly, or a matching placebo for two weeks each, in a randomized, double-blind, crossover design. A run-in period of two weeks was permitted between the two therapies during which patients continued to receive the conventional therapy without any vasodilator. At the end of each therapy period, the patients were evaluated for symptoms, New York Heart Association class, distance covered during the 6 min walk test, rating of modified Borg dyspnea score, and systolic pulmonary artery pressure using echo Doppler. The differences in the above variables at the end of sildenafil and placebo therapies were compared. Nine patients completed the study protocol. Sildenafil, compared to placebo, was associated with improved exercise tolerance as determined by the 6 min walk test (266.67+/-131.45 m v. 170+/-105 m; p<0.005), decrease in modified Borg dyspnea score (3.56+/-1.01 v. 5.11+/-1.45; p<0.01), decrease in Doppler-estimated pulmonary artery systolic pressures (55.33+/-16.52 mmHg v. 75.33+/-19.75 mmHg; p<0.005), improvement in New York Heart Association class (2 patients), and improvement in symptoms. Sildenafil was well tolerated with no untoward effects; further, no significant changes in heart rate or blood pressure occurred during the study period.\n Sildenafil improves exercise capacity and symptoms, and decreases pulmonary artery pressures in patients with primary or secondary pulmonary hypertension of varied etiology." ]	The validity of the observed effects is undermined by small participant numbers and inadequate exploration of the different disease etiologies. The effects on long term outcome such as NYHA functional class, symptoms, mortality and exercise capacity require further validation. More studies of adequate size are required before the long term effects of sildenafil on clinically important outcomes can be established.
CD004225	[ "20357374", "22183208", "8990428", "1748256" ]	[ "Prevention of gestational diabetes: feasibility issues for an exercise intervention in obese pregnant women.", "Regular exercise during pregnancy to prevent gestational diabetes: a randomized controlled trial.", "Effects of a partially home-based exercise program for women with gestational diabetes.", "Exercise in gestational diabetes. An optional therapeutic approach?" ]	[ "To examine the feasibility of an individualized exercise program to prevent gestational diabetes mellitus (GDM) in obese pregnant women.\n The study was a pilot randomized controlled trial with obese pregnant women (intervention group, individualized exercise program [n = 25]; control group, usual care [n = 25]). Average weekly energy expenditure (MET hours per week and kilocalories per week) of exercise-specific activity was assessed during pregnancy using the Pregnancy Physical Activity Questionnaire. Fasting glucose and insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were assessed at baseline and 20, 28, and 36 weeks' gestation.\n Of the women in the intervention group, 16 of 22 (73%) achieved more than 900 kcal/week of exercise-based activity at 28 weeks compared with 8 of 19 women in the control group (42%), P = 0.047. However, insulin resistance (HOMA-IR) did not differ between the groups.\n This intervention was feasible and prompted a modest increase in physical activity. However, we are not confident that this intervention would be sufficient to prevent GDM.", "To assess whether exercise during pregnancy can prevent gestational diabetes and improve insulin resistance.\n A total of 855 women in gestational week 18-22 were randomly assigned to receiving a 12-week standard exercise program (intervention group) or standard antenatal care (control group). The exercise program followed standard recommendations and included moderate-intensity to high-intensity activity 3 or more days per week. Primary outcomes were gestational diabetes and insulin resistance estimated by the homeostasis model assessment method. For the power calculation, we assumed a gestational diabetes prevalence of 9% in the control group and a prevalence of 4% in the exercise group (risk difference of 5%). Under these assumptions, a two-sample comparison with a 5% level of significance and power of 0.80 gave a study population of 381 patients in each group.\n At 32-36 weeks of gestation there were no differences between groups in prevalence of gestational diabetes: 25 of 375 (7%) in the intervention group compared with 18 of 327 (6%) in the control group (P=.52). There were no differences in insulin resistance between groups when adjusting for baseline values. Only 55% of women in the intervention group managed to follow the recommended exercise protocol. No serious adverse events related to physical exercise were seen, and the outcomes of pregnancy were similar in the two groups.\n There was no evidence that offering women a 12-week standard exercise program during the second half of pregnancy prevents gestational diabetes or improves insulin resistance in healthy pregnant women with normal body mass indexes.\n : ClinicalTrials.gov, www.clinicaltrials.gov, NCT00476567.", "To examine the effectiveness of a partially home-based, moderate-intensity aerobic exercise program for women with gestational diabetes.\n This was a randomized experimental design. Thirty-three women with gestational diabetes were randomly assigned to the exercise or the no-exercise group. Subjects underwent hemoglobin A1C assay and submaximal cycle ergometer fitness tests at baseline and at study conclusion. Subjects kept diaries of home fasting and 2-hour postprandial blood glucose determinations. Exercise subjects were asked to exercise for 30 minutes three to four times weekly at 70% of estimated maximal heart rate for the weeks of study participation. Two exercise sessions weekly were supervised by the investigator, and two were unsupervised at home. Control-group subjects were asked to maintain their current activity level.\n Daily fasting and postprandial blood glucose levels, hemoglobin A1C, incidence of exogenous insulin therapy, and incidence of newborn hypoglycemia were not different between the groups. There was a training effect in the exercise group (P = .005) but not in the control group (P = .25). A significant decline in daily grams of carbohydrate consumed was observed in the control group (P = .03), but not in the exercise group (P = .97). No complications were found in the subjects who exercised.\n A partially home-based exercise program did not reduce blood glucose levels, but did result in a modest increase in cardiorespiratory fitness. The intervention appeared safe.", "Forty-one patients with gestational diabetes requiring insulin were enrolled in a randomized study to investigate the efficacy of an exercise program in normalizing glucose tolerance. Seventeen of 21 patients completed the exercise program while maintaining normoglycemia and obviating insulin therapy. Maternal and neonatal complications did not differ between the study and control groups. The type of program described appears to be safe and can serve as a model for exercise prescription for pregnant diabetic women to attain improved glucose tolerance." ]	There is insufficient evidence to recommend, or advise against, diabetic pregnant women to enrol in exercise programs. Further trials, with larger sample size, involving women with gestational diabetes, and possibly type 1 and 2 diabetes, are needed to evaluate this intervention. [Note: The six citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]
CD003217	[ "17626040" ]	[ "Mycophenolate mofetil as adjunctive therapy for MMN patients: a randomized, controlled trial." ]	[ "Multifocal motor neuropathy (MMN) is an immune-mediated disorder characterized by slowly progressive asymmetrical limb weakness. Treatment with immunoglobulins (IVIg) leads to improvement of muscle strength. Anecdotal evidence suggests that immunosuppressive drugs as adjunctive therapy may be beneficial. Mycophenolate mofetil (MMF) is a potent and safe immunosuppressant. Safety and efficacy of MMF as adjunctive therapy for MMN patients receiving IVIg maintenance treatment were evaluated in a randomized controlled trial. MMN patients responding to IVIg treatment were eligible for randomization. Muscle strength and functional status were assessed at monthly intervals for 1 year. Three months after the start of MMF or placebo treatment, IVIg doses were reduced stepwise, until a deterioration of functioning or decline in muscle strength could be observed. An IVIg dose reduction of 50% during adjunctive treatment was defined as a primary endpoint. Secondary outcome measures were improvement in muscle strength and functional status after 3 months and reduction of anti GM1-IgM titres after 12 months of MMF treatment. Twenty-eight patients were randomized. One patient allocated to MMF reached the primary endpoint of 50% IVIg dose reduction. After 12 months IVIg reduction did not differ significantly between the two treatment groups. Patients did not experience drug toxicity and none of the patients showed significant disease progression after 12 months. Muscle strength and functional scores after 3 months and anti GM1-IgM titres after 12 months did not change. Adjunctive treatment of MMN patients with MMF at a dose of 1 g twice daily is safe but does not alter disease course or allow significant reduction of IVIg doses." ]	According to moderate quality evidence, mycophenolate mofetil did not produce significant benefit in terms of reducing need for intravenous immunoglobulin or improving muscle strength. Trials of other immunosuppressants should be undertaken.
CD001893	[ "7533484", "11573049", "2919775", "11684971", "1378707", "8874561", "16192774", "3233467", "3284266", "8904263", "2922985", "10593465", "9842825", "7566849", "16394700", "9113175", "15196107", "9743393", "3564873", "14500163", "15636813" ]	[ "Intravenous versus epidural administration of hydromorphone. Effects on analgesia and recovery after radical retropubic prostatectomy.", "Effect of epidural anesthesia and analgesia on perioperative outcome: a randomized, controlled Veterans Affairs cooperative study.", "Epidural analgesia with bupivacaine reduces postoperative paralytic ileus after hysterectomy.", "Double-masked randomized trial comparing alternate combinations of intraoperative anesthesia and postoperative analgesia in abdominal aortic surgery.", "Epidural patient-controlled analgesia: an alternative to intravenous patient-controlled analgesia for pain relief after cesarean delivery.", "Myoelectric activity in the stomach and duodenum after epidural administration of morphine or bupivacaine.", "Intraoperative epidural analgesia combined with ketamine provides effective preventive analgesia in patients undergoing major digestive surgery.", "Effect of continuous postoperative epidural analgesia on intestinal motility.", "Opioid treatment for radiating cancer pain: oral administration vs. epidural techniques.", "Does morphine premedication influence the pain and consumption of postoperative analgesics after total knee arthroplasty?", "Effects of epidural bupivacaine and epidural morphine on bowel function and pain after hysterectomy.", "Intraarticular, epidural, and intravenous analgesia after total knee arthroplasty.", "Postoperative analgesia with intramuscular morphine at fixed rate versus epidural morphine or sufentanil and bupivacaine in patients undergoing major abdominal surgery.", "Randomized trial of epidural versus intravenous analgesia during labor.", "Thoracic epidural versus intravenous patient-controlled analgesia after cardiac surgery: a randomized controlled trial on length of hospital stay and patient-perceived quality of recovery.", "Anesthetic quality during cesarean section following subarachnoid or epidural administration of bupivacaine with or without fentanyl.", "Effects of post-operative pain treatment using non-steroidal anti-inflammatory analgesics, opioids or epidural blockade on systemic and local immune responses in children.", "Epidural bupivacaine-morphine analgesia versus patient-controlled analgesia following abdominal aortic surgery: analgesic, respiratory, and myocardial effects.", "The effect of bupivacaine and morphine on pain and bowel function after colonic surgery.", "Intraoperative intravenous ketamine in combination with epidural analgesia: postoperative analgesia after renal surgery.", "Spinal or epidural anaesthesia for elective caesarean section? A Swedish experience." ]	[ "It remains unclear whether epidural administration of hydromorphone results in spinal analgesia or clinical benefit when compared with intravenous administration. Therefore, we undertook this study to determine whether epidural administration of hydromorphone resulted in decreased opioid requirement, improved analgesia, reduced side effects, more rapid return of gastrointestinal function, or shorter duration of hospital stay than intravenous administration.\n Sixteen patients undergoing radical retropubic prostatectomy were randomized in a double-blind manner to receive either intravenous or epidural hydromorphone via patient-controlled analgesia (PCA) for postoperative analgesia. All patients underwent a standardized combined epidural and general anesthetic and all received ketorolac for 72 h postoperatively. To decrease variability, patients were cared for according to a standardized protocol and were deemed ready for discharge according to prospectively defined criteria.\n Patients in the intravenous PCA group required approximately twice as much opioid than the epidural PCA group (P < 0.008), but there were no differences between groups in pain scores or patient satisfaction. Epidural administration resulted in a greater incidence of pruritus (P = 0.02). Gastrointestinal function recovered quickly in all patients with little variation, and there were no differences between groups. All patients were deemed ready for discharge by the third postoperative day, and removal of surgical drains was the last discharge criterion reached in all patients.\n Our results indicate that epidural administration of hydromorphone results in spinally mediated analgesia. However, epidural administration did not provide significant benefits in terms of postoperative analgesia, recovery of gastrointestinal function, or duration of hospitalization. Furthermore, we suggest that radical retropubic prostatectomy no longer be used as a model to assess the effects of analgesic technique on postoperative recovery, because control of discharge criteria revealed that hospital discharge was primarily dependent on removal of surgical drains.", "To test the hypothesis that epidural anesthesia and postoperative epidural analgesia decrease the incidence of death and major complications during and after four types of intraabdominal surgical procedures.\n Even though many beneficial aspects of epidural anesthesia have been reported, clinical trials of epidural anesthesia for outcome of surgical patients have shown conflicting results.\n The authors studied 1,021 patients who required anesthesia for one of the intraabdominal aortic, gastric, biliary, or colon operations. They were assigned randomly to receive either general anesthesia and postoperative analgesia with parenteral opioids (group 1) or epidural plus light general anesthesia and postoperative epidural morphine (group 2). The patients were monitored for death and major complications during and for 30 days after surgery, as well as for postoperative pain, time of ambulation, and length of hospital stay.\n Overall, there was no significant difference in the incidence of death and major complications between the two groups. For abdominal aortic surgical patients, unlike the other three types of surgical patients, the overall incidence of death and major complications was significantly lower in group 2 patients (22%) than in group 1 patients (37%), stemming from differences in the incidence of new myocardial infarction, stroke, and respiratory failure between the two groups. Overall, group 2 patients received significantly less analgesic medication but had better pain relief than group 1 patients. In group 2 aortic patients, endotracheal intubation time was 13 hours shorter and surgical intensive care stay was 3.5 hours shorter.\n The effect of anesthetic and postoperative analgesic techniques on perioperative outcome varies with the type of operation performed. Overall, epidural analgesia provides better postoperative pain relief. Epidural anesthesia and epidural analgesia improve the overall outcome and shorten the intubation time and intensive care stay in patients undergoing abdominal aortic operations.", "This study was undertaken to compare the effects of postoperative bupivacaine epidural analgesia with those of intermittent injections of ketobemidone (a synthetic opioid) on postoperative bowel motility in patients who had had hysterectomies. The epidural group (N = 20) received continuous epidural anesthesia with bupivacaine postoperatively for 26-30 hours and the control group (N = 20) received intermittent injections of ketobemidone for postoperative pain relief. Postoperative bowel movements and propulsive colonic motility were estimated from the first passage of flatus and feces and by following radiopaque markers by serial abdominal radiographs. In the epidural group, the times for first passing of flatus (31 +/- 22 hours; mean +/- SD) and feces (70 +/- 44 hours) were significantly shorter than in the control group (flatus 58 +/- 14 hours and feces 103 +/- 26 hours). The average position of the markers was significantly more distally in the epidural group immediately after operation and the markers continued to move forward during the first postoperative day. In the control group, the markers did not move during this period. The results demonstrate that postoperative bowel peristalsis returned earlier in the patients given epidural analgesia with bupivacaine for pain relief than in patients given a narcotic.", "Improvement in patient outcome and reduced use of medical resources may result from using epidural anesthesia and analgesia as compared with general anesthesia and intravenous opioids, although the relative importance of intraoperative versus postoperative technique has not been studied. This prospective, double-masked, randomized clinical trial was designed to compare alternate combinations of intraoperative anesthesia and postoperative analgesia with respect to postoperative outcomes in patients undergoing surgery of the abdominal aorta.\n One hundred sixty-eight patients undergoing surgery of the abdominal aorta were randomly assigned to receive either thoracic epidural anesthesia combined with a light general anesthesia or general anesthesia alone intraoperatively and either intravenous or epidural patient-controlled analgesia postoperatively (four treatment groups). Patient-controlled analgesia was continued for at least 72 h. Protocols were used to standardize perioperative medical management and to preserve masking intraoperatively and postoperatively. A uniform surveillance strategy was used for the identification of prospectively defined postoperative complications. Outcome evaluation included postoperative hospital length of stay, direct medical costs, selected postoperative morbidities, and postoperative recovery milestones.\n Length of stay and direct medical costs for patients surviving to discharge were similar among the four treatment groups. Postoperative outcomes were similar among the four treatment groups with respect to death, myocardial infarction, myocardial ischemia, reoperation, pneumonia, and renal failure. Epidural patient-controlled analgesia was associated with a significantly shorter time to extubation (P = 0.002). Times to intensive care unit discharge, ward admission, first bowel sounds, first flatus, tolerating clear liquids, tolerating regular diet, and independent ambulation were similar among the four treatment groups. Postoperative pain scores were also similar among the four treatment groups.\n In patients undergoing surgery of the abdominal aorta, thoracic epidural anesthesia combined with a light general anesthesia and followed by either intravenous or epidural patient-controlled analgesia, offers no major advantage or disadvantage when compared with general anesthesia alone followed by either intravenous or epidural patient-controlled analgesia.", "Epidural administration of an opioid analgesic by means of a patient-controlled analgesia (PCA) system was compared with conventional intravenous PCA for pain relief after cesarean delivery. One hundred seventeen healthy women were randomly assigned to receive hydromorphone either intravenously (IV-PCA) or epidurally (EPI-PCA) after cesarean delivery with epidural bupivacaine for operative anesthesia. The hydromorphone requirements were 3.4 and 4.2 times more in the IV-PCA group on the first (P less than 0.01) and second (P less than 0.01) postoperative days, respectively. The mean number (+/- SD) of PCA demands during the first 24 h after the operation was 105 (+/- 88) for the IV-PCA group and 33 (+/- 48) for the EPI-PCA group (P less than 0.01). This difference was also significant 24-48 h after surgery. Although the EPI-PCA group utilized significantly less opioid medication, pain and sedation scores were similar in the two treatment groups; however, a significantly larger percentage of patients in the IV-PCA group (46% vs 22%) stated that they felt drowsy during the first postoperative day. Pruritus was reported more frequently in the EPI-PCA (67%) than in the IV-PCA (33%) group. Nausea was experienced by only 10% of patients in the IV-PCA and 6% in the EPI-PCA group. There was no evidence of postoperative respiratory depression, with minimal oxygen saturation values of 93% (+/- 3%) and 94% (+/- 1%) in the IV-PCA and EPI-PCA groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)", "Gastric emptying is delayed in patients receiving postoperative pain relief with epidural morphine compared to patients receiving epidural bupivacaine. The electrophysiological basis for this effect is unknown. The aim of this study was to compare the effects of epidural morphine with epidural bupivacaine on gastroduodenal myoelectric activity (EMG) in patients after surgery.\n Fourteen patients with epidural analgesia who underwent open cholecystectomy were randomly assigned to receive either epidural morphine (EM) or epidural bupivacaine (EB) for postoperative pain relief. During surgery EMG electrodes were placed in the subserosa in the antrum and duodenum and the EMG registration started 3.5 hours after the end of surgery. Gastric emptying measured with the acetaminophen test was studied in the morning the day after surgery.\n The spike activity in the antrum was significantly lower 160-340 minutes after the administration of morphine in the EM-group compared to the activity in the EB-group (P < 0.04). The incidence of regular slow wave rhythm in the antrum was significantly lower 160-520 minutes after the administration of morphine in the EM-group compared to the EB-group (P < 0.03). Duodenal Phase III activity measured with EMG was significantly more frequent during 160-520 minutes after the morphine administration in the EM-group compared to the EB-group (P < 0.02). The acetaminophen absorption was significantly delayed in the epidural morphine group compared to the epidural bupivacaine group.\n Gastroduodenal electromyographic activity was significantly changed during epidural morphine compared to epidural bupivacaine. The delayed gastric emptying during epidural morphine may be explained by decreased and uncoordinated contractile activity in the antrum, shown by decreased spike activity and irregular slow wave rhythm. The increased pressure activity in the duodenum, shown by increased Phase III activity, may also impair gastric emptying.", "As a broader definition of preemptive analgesia, preventive analgesia aims to prevent the sensitization of central nervous system, hence the development of pathologic pain after tissular injury. To demonstrate benefits from preventive treatment, objective measurement of postoperative pain such as wound hyperalgesia and persistent pain should be evaluated. The current study assessed the role and timing of epidural analgesia in this context.\n In a randomized, double-blinded trial, 85 patients scheduled to undergo neoplastic colonic resection were included. All the patients received a thoracic epidural catheter, systemic ketamine at a antihyperalgesic dose, and general anesthesia. Continuous infusion of analgesics belonging to the same class was administered by either intravenous or epidural route before incision until 72 h after surgery. Patients were allocated to four groups to receive intraoperative intravenous lidocaine-sufentanil-clonidine or epidural bupivacaine-sufentanil-clonidine followed postoperatively by either intravenous (lidocaine-morphine-clonidine) or epidural (bupivacaine-sufentanil-clonidine) patient-controlled analgesia. Postoperative pain scores (visual analog scale), analgesic consumption, wound area of punctuate hyperalgesia, residual pain, and analgesics needed from 2 weeks until 12 months were recorded.\n Analgesic requirements, visual analog scale scores, and area of hyperalgesia were significantly higher in the intravenous treatment group (intravenous-intravenous), and more patients reported residual pain from 2 weeks until 1 yr (28%). Although postoperative pain measurements did not differ, postoperative epidural treatment (intravenous-epidural) was less effective to prevent residual pain at 1 yr (11%; P = 0.2 with intravenous-intravenous group) than intraoperative one (epidural-epidural and epidural-intravenous groups) (0%; P = 0.01 with intravenous-intravenous group).\n Combined with an antihyperalgesic dose of ketamine, intraoperative epidural analgesia provides effective preventive analgesia after major digestive surgery.", "The effect of postoperative epidural bupivacaine on intestinal motility was studied by measuring the transit time of barium contrast through the intestines in 16 patients after resection of the left colon and/or rectum. Fourteen patients served as controls and received postoperative injections of pentazocine. Mean transit time through the intestinal tract was 35 h in the epidural group and 150 h in the control group, a difference that is significant at the 0.1 per cent level. The average time before passage of flatus and faeces was different between the two groups at the 0.1 per cent level. We conclude that postoperative epidural bupivacaine constitutes an effective means of analgesia after colorectal surgery and is associated with a short duration of intestinal paralysis.", "In order to determine the optimal pain treatment for patients with cancer involvement of the brachial or lumbar nerve plexuses, a prospective comparative study was carried out using peroral opioid therapy (SO), epidural opioid by a conventional tunnelled epidural catheter (CE) or an epidural catheter connected to an implanted injection port (Port). Pain relief, measured by a visual analog scale (VAS), was similar and adequate in every group already after the first 24 h. CNS side-effects were less frequent and the Karnofsky performance grades slightly superior in the epidural groups. Occlusion and catheter disconnection complicated the pain therapy of five epidural port patients. Epidural dislocation occurred three times in the conventional epidural group. One local infection in the CE group and two in the Port group were recorded. However, no signs of epidural infection were seen at autopsy. The results suggest that due to a lower incidence of side-effects, epidural catheter techniques are superior to peroral opioid in treating pain in these patients. However, complete pain relief was not achieved in all patients, suggesting neurogenic, non-nociceptive pain components. Both epidural techniques seem suitable for long-term pain therapy. Technical improvements are needed in the epidural catheter and the port. The long-term epidural catheter does not seem to cause any major changes in the histology of the dura mater or the connective tissue of the epidural space.", "Evidence of pre-emptive analgetic effect of opioid would offer great potential benefit to patients with postoperative pain, a better pain relief with less opioid. The aim of this double blind randomised trial was to study the effect of intramuscular morphine premedication on postoperative pain. Forty-one patients undergoing total knee arthroplasty were randomly allocated to four groups. Two groups received epidural morphine, 4 mg immediately after operation and 3 mg ten hours later, and two groups the same volume of saline. All patients had access to intravenous PCA-fentanyl. One epidural morphine and one epidural saline group (PreEpiMo and PreMo, respectively) received morphine, 0.14 mg/kg i.m. as premedication. Pain was measured with a visual analogue scale (VAS). Respiration was monitored by means of pulseoximetry, arterial blood gas analysis and rate of breathing. Morphine premedication reduced postoperative pain in the immediate postoperative period in patients with epidural placebo (PreMo), but the effect was absent in patients with PreEpiMo. Epidural morphine (EpiMo) provided stable analgesia with reduced need of PCA-fentanyl. Two patients (10%) (one in EpiMo and one in PreEpiMo) developed respiratory depression requiring naloxone treatment. The dosage of epidural morphine used in this study was a likely explanation of this depression. Nausea, vomiting, itching and urinary retention were the most frequent side effects without significant differences between the groups. In conclusion, morphine premedication had a temporary rest effect on the postoperative pain. Epidural morphine provides a better analgesia than intravenous PCA-fentanyl.", "A comparison was made of the effects of continuous epidural analgesia with bupivacaine and intermittent epidural morphine on bowel function after abdominal hysterectomy. The duration of postoperative ileus was assessed as the time from the end of operation to the first postoperative passage of flatus and feces. Twenty-two patients were randomly allocated to two equal groups. An \"epidural morphine\" group received general anesthesia and epidural morphine for postoperative pain relief, and an \"epidural bupivacaine\" group was given combined general anesthesia and epidural anesthesia with 0.5% bupivacaine intraoperatively and epidural analgesia with 0.25% bupivacaine postoperatively. Epidural morphine or bupivacaine was given for 42 h postoperatively. Pain intensity (visual analog scale) was low in both groups, but lower (P less than 0.05) in the epidural bupivacaine group. The time to first passage of flatus was 22 +/- 16 h in the epidural bupivacaine group and 56 +/- 22 h in the epidural morphine group (P less than 0.001). The time to first postoperative passage of feces was shorter (P less than 0.05) in the former than in the latter 57 +/- 44 h vs 92 +/- 22 h). The patients of the epidural bupivacaine group started intake of oral fluids earlier (P less than 0.01) and to a greater extent (P less than 0.05) than those in the epidural morphine group. It is concluded that the duration of postoperative ileus after hysterectomy is shorter when epidural bupivacaine is given for postoperative pain relief than when this is achieved by epidural morphine.", "After total knee arthroplasty, patients regularly suffer from severe pain. It is unclear whether epidural or systemic pain therapy is superior in terms of postoperative pain relief, patients' comfort and side effects. A new therapeutic approach, intraarticular opioids, has been suggested with the detection of opioid receptors in inflamed tissue. This method has proven suitable for clinical use in small operations (e.g. knee arthroscopy). In this study, we compared epidural analgesia and intraarticular application of morphine plus \"on-demand\" intravenous analgesia to \"on-demand\" intravenous analgesia alone.\n Thirty-seven patients, scheduled for total knee arthroplasty, were randomly assigned to three treatment groups: in group 1 (EPI) patients received bolus doses of morphine via an epidural catheter; in group 2 (IA) an intraarticular bolus of 1 mg of morphine was applied at the end of the operation with subsequent use of a patient-controlled analgesia (PCA) pump; group 3 (Control), in which only PCA was provided, served as control for both analgesic procedures. Main outcome measures included visual analogue pain scales, total morphine consumption, and stress hormones.\n No statistically significant differences in visual analogue pain scales could be detected between the three groups. Application of intraarticular morphine did not reduce the amount of analgesics required for postoperative analgesia as compared to intravenous analgesia alone. Application of epidural morphine significantly suppressed beta-endorphine release, but did not significantly influence other stress hormones as compared to the control group.\n Epidural and intravenous analgesia after total knee arthroplasty are equivalent methods of pain relief. In major orthopaedic procedures, application of intraarticular morphine does not reduce analgesic requirements.", "We assessed the efficacy and side effects of postoperative analgesia with three different pain regimens in 90 patients undergoing major abdominal surgery. The patients were randomly assigned to one of three groups: epidural morphine (EM) or sufentanil (ES), both combined with bupivacaine, or IM morphine (IM) at fixed intervals. Before incision, patients in the epidural groups received sufentanil or morphine in bupivacaine via a thoracic catheter, followed by a continuous infusion 1 h later. General anesthesia consisted of N2O/O2 and isoflurane for all groups. Patients in all groups received IV sufentanil as part of their anesthetic management. Patients in the IM group received IV sufentanil 1 microg/kg before incision, and patients in all groups received sufentanil 10 microg for inadequate analgesia. Postoperatively, the epidural or IM treatment was continued for > or =5 days. Postoperative analgesia at rest and during coughing and movement was significantly better in the epidural groups than in the IM group during the 5 consecutive days. There were no significant differences between the epidural groups. The incidence of most side effects was similar in all groups. We conclude that epidural analgesia provided better pain relief than IM analgesia, even if the latter was optimized by fixed-dose administration at fixed intervals and included adjustments on demand. Epidural sufentanil and morphine, both combined with bupivacaine, seemed to be equally effective with similar side effects.\n Postoperative analgesia with epidural sufentanil or morphine and bupivacaine after major abdominal surgery seemed to be better than the conventional method of IM morphine treatment, despite optimal administration, i.e., fixed doses at fixed intervals with regular adjustments. Analgesic efficacy and side effects of epidural sufentanil and morphine were similar.", "To compare the effects of epidural analgesia with intravenous (IV) analgesia on the outcome of labor.\n Thirteen hundred thirty women with uncomplicated term pregnancies and in spontaneous labor were randomized to be offered epidural bupivacaine-fentanyl or IV meperidine analgesia during labor.\n Comparison of the allocation groups by intent to treat revealed a significant association between epidural allocation and operative delivery for dystocia. However, only 65% of each randomization group accepted the allocated treatment. Four hundred thirty-seven women accepted and received meperidine as allocated, and they were compared with 432 women accepting epidural allocation. Significant associations resulted between epidural administration and prolongation of labor, increased rate of oxytocin administration, chorioamnionitis, low forceps, and cesarean delivery. Because of the high rate of noncompliance with treatment allocation, a multifactorial regression analysis was performed on the entire cohort, and a twofold relative risk of cesarean delivery persisted in association with epidural treatment. The impact of epidural treatment on cesarean delivery was significant for both nulliparous and parous women (risk ratios 2.55 and 3.81, respectively). Epidural analgesia provided significantly better pain relief in labor than did parenteral meperidine.\n Although labor epidural analgesia is superior to meperidine for pain relief, labor is prolonged, uterine infection is increased, and the number of operative deliveries are increased. A two- to fourfold increased risk of cesarean delivery is associated with epidural treatment in both nulliparous and parous women.", "Perioperative thoracic epidural analgesia reduces stress response and pain scores and may improve outcome after cardiac surgery. This prospective, randomized trial was designed to compare the effectiveness of patient-controlled thoracic epidural analgesia with patient-controlled analgesia with intravenous morphine on postoperative hospital length of stay and patients' perception of their quality of recovery after cardiac surgery.\n One hundred thirteen patients undergoing elective cardiac surgery were randomly assigned to receive either combined thoracic epidural analgesia and general anesthesia followed by patient-controlled thoracic epidural analgesia or general anesthesia followed by to patient-controlled analgesia with intravenous morphine. Postoperative length of stay, time to eligibility for hospital discharge, pain and sedation scores, degree of ambulation, lung volumes, and organ morbidities were evaluated. A validated quality of recovery score was used to measure postoperative health status.\n Length of stay and time to eligibility for hospital discharge were similar between the groups. Study groups differed neither in postoperative global quality of recovery score nor in five dimensions of quality of recovery score. Time to extubation was shorter (P < 0.001) and consumption of anesthetics was lower in the patient-controlled thoracic epidural analgesia group. Pain relief, degree of sedation, ambulation, and lung volumes were similar between the study groups. There was a trend for lower incidences of pneumonia (P = 0.085) and confusion (P = 0.10) in the patient-controlled thoracic epidural analgesia group, whereas cardiac, renal, and neurologic outcomes were similar between the groups.\n In elective cardiac surgery, thoracic epidural analgesia combined with general anesthesia followed by patient-controlled thoracic epidural analgesia offers no major advantage with respect to hospital length of stay, quality of recovery, or morbidity when compared with general anesthesia alone followed by to patient-controlled analgesia with intravenous morphine.", "It is often assumed that subarachnoid administration of local anesthetics produces a more profound blockade than epidural anesthesia. Furthermore, the addition of fentanyl has been reported to increase preferentially intraoperative analgesia. In the present study we set out to study these two issues in a randomized and controlled study with respect to perceived pain and discomfort during surgery and postoperative pain.\n In the present study, 100 parturients subjected to elective cesarean section, 34 nullipara and 66 multipara, received one out of four combinations of the local anesthetic bupivacaine and the opioid fentanyl; group A--bupivacaine 12.5 mg + 10 micrograms fentanyl subarachnoidally, group B--bupivacaine 12.5 mg + saline subarachnoidally, group C--bupivacaine 100 mg + 100 micrograms fentanyl epidurally, group D--bupivacaine 100 mg + saline epidurally; N = 25 in each group. Pain intensity and discomfort during surgery was assessed with a visual analogue scale (VAS). Postoperative pain intensity and need for analgesics postoperatively, ketobemidone, was registered for 24 h following surgery.\n Intraoperative pain intensity and discomfort did not differ significantly between parturients in any of the four groups Postoperative pain was significantly more intense in parturients receiving local anesthetics subarachnoidally as compared to the epidural groups during the first 6-h period. This difference was also reflected in a significantly increased consumption of analgesics during this period. No significant differences between the groups were observed with regard to hemodynamics (blood pressure), respiration (oxygen saturation) or other effects such as nausea or itching. All neonates had normal Apgar and neonatal adaptive capacity scores (NACS).\n We conclude that subarachnoidal (12.5 mg) and epidural (100 mg) injections with bupivacaine both produced adequate anesthetic quality in women undergoing elective cesarean section. The addition of fentanyl (10 micrograms subarachnoidally or 100 micrograms epidurally) did not significantly improve the quality of these already profound blockades.", "Many studies have been carried out on the effects of anaesthetic drugs and methods on the immune response, but pain and its relief also affect the immune response. We measured systemic immune responses in the blood circulation and local responses in the surgical wound when non-steroidal anti-inflammatory analgesics (NSAIDs), opioids or epidural blockade was used in the peri-operative treatment of pain.\n Responses were measured in 51 children, aged from 2 to 12 years and undergoing major surgery under balanced anaesthesia. Bolus doses of diclofenac intravenously (i.v.) and rectally (NSAID group), continuous i.v. infusion of oxycodone (opioid group) or continuous epidural infusion of bupivacaine + fentanyl (epidural group) were used peri-operatively for pain relief.\n The only difference related to the analgesic method was shorter duration of post-operative leucocytosis and lower phytohaemagglutinin (PHA)-induced lymphocyte proliferative responses in peripheral blood in the opioid group than in the NSAID or epidural groups. By contrast, time-related alterations were seen overall in leucocyte and differential counts, lymphocyte and their subset counts, lymphocyte proliferative responses, and in serum cortisol, C-reactive protein, plasma interleukin-6 and group II phospholipase A2 concentrations and in the appearance of different cell types in the wound.\n Post-operative pain treatments using diclofenac (NSAID), oxycodone (opioid) and epidural blockade have basically similar effects on systemic and local immune responses with only slight, probably clinically unimportant differences in children undergoing surgery under general anaesthesia.\n Copyright 2004 Acta Anaesthesiologica Scandinavica", "The efficacy and effects of epidural analgesia compared with patient-controlled analgesia (PCA) have not been reported in patients undergoing major vascular surgery. We compared the effects of epidural bupivacaine-morphine with those of intravenous PCA morphine after elective infrarenal aortic surgery.\n Forty patients classified as American Society of Anesthesiologists physical status 2 or 3 received general anesthesia plus postoperative PCA using morphine sulfate (group PCA; n = 21) or general anesthesia plus perioperative epidural morphine-bupivacaine (group EPI; n = 19) during a period of 48 h. During operation, EPI patients received 0.05 mg/kg epidural morphine and 5 ml 0.25% bupivacaine followed by an infusion of 0.125% bupivacaine with 0.1% morphine (0.1 mg/ ml); group PCA received 0.1 mg/kg intravenous morphine sulfate. Continuous electrocardiographic monitoring (V4 and V5 leads) was performed from the night before surgery until 48 h afterward. Respiratory inductive plethysmographic data were recorded after tracheal extubation. Visual analog pain scores at rest and after movement were performed every 4 h after extubation.\n Nurse-administered intravenous morphine and time to tracheal extubation were less in group EPI, as were visual analog pain scores at rest and after movement from 20 to 48 h. Complications and the duration of intensive care unit and hospital stay were comparable. There was a similar, low incidence of postoperative apneas, slow respiratory rates, desaturation, and S-T segment depression.\n Epidural morphine-bupivacaine is associated with reduced early postoperative intravenous opioid requirements, more rapid tracheal extubation, and superior analgesia after abdominal aortic surgery, with comparable respiratory effects.", "Sixty patients scheduled for colonic surgery were randomly allocated to four groups according to postoperative pain medication: I. Control group, the patients received oxycodone intramuscularly (0.15 mg kg-1) on request. II. Epidural bupivacaine (0.25%) continuously administered by infusion pump, 4-6 ml h-1, for 48 h. III. Epidural morphine, 2-6 mg, at the end of operation and repeated on the first and second postoperative mornings. IV. Epidural morphine, 2-6 mg per die, administered for 48 h continuously by infusion pump. All patients received a balanced anaesthesia with enflurane, fentanyl and vecuronium. Postoperatively, intramuscular oxycodone was given on request. There were no significant differences between the groups in changes in peak flow, spirometry and blood-gas analyses postoperatively. Pain intensity (visual analogue scale) was lower in Groups II and III at 3 h and in Group IV at 24 h compared to the control Group I. All the epidurally treated groups needed less additional analgesics than the control Group I. Postoperatively bowel movements occurred on the second day in Group II (bupivacaine) as compared to the fourth day in all other groups (P less than 0.05).", "We designed this double-blinded, randomized, controlled study to evaluate the effect of small-dose ketamine IV in combination with epidural morphine and bupivacaine on postoperative pain after renal surgery. An epidural catheter was inserted, and the administration of morphine and bupivacaine was started before surgery. Forty patients were assigned to one of two groups (ketamine or control). The ketamine group was administered a ketamine bolus and infusion during surgery. The median visual analog pain scale (VAS) scores at rest were significantly lower in the ketamine group during the first 6 h (P < 0.01). VAS pain scores on coughing were also significantly lower in the ketamine group (P < 0.01). Cumulative postoperative total analgesic consumption was less in the ketamine group on Days 1 and 2 (P < 0.001). The first analgesic demand time was shorter in the control group (9.2 +/- 11.5 min) than in the ketamine group (22.3 +/- 17.1 min) (P < 0.0001). The incidence of nausea and pruritus was more frequent in the control group (P < 0.05). In conclusion, postoperative analgesia was more effective when spinal cord and brain sensitization were blocked by a combination of epidural morphine/bupivacaine and IV ketamine.\n Renal nociception conducted multisegmentally by both the spinal nerves (T10 to L1) and the vagus nerve cannot be blocked by epidural analgesia alone. We demonstrated that IV ketamine had an improved analgesic or opioid-sparing effect when it was combined with epidural bupivacaine and morphine after renal surgery.", "Ninety seven women undergoing elective lower segment caesarean section were randomly divided into two groups, group 1 received spinal anaesthesia with hyperbaric bupivacaine and group 2 received mepivacaine 20 mg/ml with adrenaline 5 microg/ml via an epidural catheter. All patients were given a preload of Ringer acetate and Macrodex prior to onset of anaesthesia. Ephedrine 5 mg was given if the systolic blood pressure fell below 100 mmHg. There was a small (<30%) but significant (P<0.01) fall in blood pressure in both groups of women. Six women in the epidural group required supplemental analgesics during the operation compared to only 1 patient in the spinal group (P<0.01). Muscle relaxation was judged to be inadequate in 3 patients in the spinal group and in 5 patients in the epidural group. One patient in the spinal group had a characteristic post-spinal headache lasting 3 days. The injection-delivery time was shorter (P<0.01) in the spinal group compared to the epidural group. The Apgar scores at 1 and 5 min were similar in both groups. The results from our study suggest that spinal anaesthesia is a good alternative to epidural anaesthesia for elective caesarean section. A fall in blood pressure, which is equally possible in both groups of patients, should be prevented by adequate fluid preload and treated immediately by intravenous ephedrine." ]	Administration of epidural local anaesthetics to patients undergoing laparotomy reduce gastrointestinal paralysis compared with systemic or epidural opioids, with comparable postoperative pain relief. Addition of opioid to epidural local anaesthetic may provide superior postoperative analgesia compared with epidural local anaesthetics alone. The effect of additional epidural opioid on gastrointestinal function is so far unsettled. Randomized, controlled trials comparing the effect of combinations of epidural local anaesthetic and opioid with epidural local anaesthetic alone on postoperative gastrointestinal function and pain are warranted.
CD001241	[ "22664861", "15181294", "15574620", "10064664", "3081868" ]	[ "Randomized controlled trial of slow vs rapid enteral feeding advancements on the clinical outcomes of preterm infants with birth weight 750-1250 g.", "Slow versus fast enteral feed advancement in very low birth weight infants: a randomized control trial.", "Randomized, controlled trial of slow versus rapid feeding volume advancement in preterm infants.", "Randomized trial of \"slow\" versus \"fast\" feed advancements on the incidence of necrotizing enterocolitis in very low birth weight infants.", "Early enteral feeding does not affect the incidence of necrotizing enterocolitis." ]	[ "To evaluate the effect of slow vs rapid rates of advancement of enteral feed volumes on the clinical outcomes in preterm infants with 750-1250 g birth weight.\n A total of 92 stable neonates 750-1250 g and gestational age <32 weeks were randomly allocated to enteral feeding advancement of 20 mL/kg/d (n = 46) or 30 mL/kg/d (n = 46). The primary outcome was days to reach full enteral feeding, defined as 180 mL/kg/d. Secondary outcomes included rates of necrotizing enterocolitis (NEC) and culture-proven sepsis, days of parenteral nutrition (PN), length of hospital stay, and growth end points.\n Neonates in the rapid-feeding advancement group achieved full enteral volume of feedings earlier than the slower advancement group. They received significantly fewer days of PN, exhibited a shorter time to regain birth weight, and had a shorter duration of hospital stay. The incidence of NEC and the number of episodes of feeding intolerance were not significantly different between the groups, whereas the incidence of culture-proven late-onset sepsis was significantly less in infants receiving a rapid feeding advancement. Excluding infants who were small for gestational age at birth, the incidence of extrauterine growth restriction was significantly reduced in the rapid-advancement group at 28 days and at hospital discharge.\n Rapid enteral feeding advancements in 750-1250 g birth weight infants reduce the time to reach full enteral feeding and the use of PN administration. Rapid-advancement enteral feed also decreases extrauterine growth restriction with improved short-term outcomes for these high-risk infants.", "To evaluate the tolerance of rapid advancement of enteral feeds in VLBW babies.\n Tertiary teaching hospital.\n Randomized controlled trial.\n All stable neonates with birth weight less than 1250 grams were included in the study. The primary outcome variable was the time taken to achieve full enteral feeds (defined as 180 ml/kg/day). The secondary outcome variables were incidence of Necrotizing enterocolitis (NNEC) and incidence of apnea. At 48 hours, the infants were randomized into the slow advancement group (enteral feeds advanced by increments of 15 ml/kg/day) or fast advancement group (enteral feeds advanced by increments of 30 ml/kg/day). The monitoring during feeding included daily weight record, two hourly abdominal girth charting, gastric aspirates, apnea, time taken to reach full enteral feedings and for NNEC.\n There were 53 infants who were enrolled for the study (27 in the fast advancement group and 26 in the slow advancement group). In the fast advancement group, 20 percent completed the trial; whereas 14 (53.8 percent;) in the slow advancement group completed the study. The two groups were comparable for birth weights, gestational age, sex, intrauterine growth status, Apgar and CRIB scores. The infants in the fast group reached full enteral intake of 180 ml/kg/day significantly earlier (10 +/- 1.8 days) than in the slow group (14.8 +/- 1.5 days). The two groups were comparable for episodes of feed intolerance, apnea, NNEC. Infants in the fast group regained birth weight significantly earlier (median 18 days) than in the slow advancement group (median 23 days).\n Stable VLBW neonates can tolerate rapid advancements of enteral feeding without increased risk of adverse effects.", "To determine whether infants who are fed initially and advanced at 30 mL/kg per day (intervention) take fewer days to get to full feedings than those who are fed initially and advanced at 20 mL/kg per day (control), without increasing their incidence of feeding complications and necrotizing enterocolitis (NEC). We also examined whether these infants regain birth weight earlier, have fewer days of intravenous fluids, and a have shorter hospital stay.\n A randomized, controlled, single-center trial was conducted in a Neonatal Intensive Care Unit of a community-based county hospital in Houston, Texas. Infants between 1000 and 2000 g at birth, gestational age < or =35 weeks, and weight appropriate for gestational age were allocated randomly to feedings of expressed human milk or Enfamil formula starting and advanced at either 30 mL/kg per day or 20 mL/kg per day. Infants remained in the study until discharge or development of stage > or =IIA NEC.\n A total of 155 infants were enrolled: 72 infants in the intervention group and 83 in the control group. Infants in the intervention group achieved full-volume feedings sooner (7 vs 10 days, median), regained birth weight faster (11 vs 13 days, median), and had fewer days of intravenous fluids (6 vs 8 days, median). Three infants in the intervention group and 2 control infants developed NEC for an overall incidence of 3.2% (relative risk: 1.73; 95% confidence interval: 0.30-10.06).\n Among infants between 1000 and 2000 g at birth, starting and advancing feedings at 30 mL/kg per day seems to be a safe practice and results in fewer days to reach full-volume feedings than using 20 mL/kg per day. This intervention also leads to faster weight gain and fewer days of intravenous fluids.", "To determine whether the rate of feed advancement affects the incidence of necrotizing enterocolitis (NEC).\n Prospective randomized controlled trial involving 185 formula-fed infants with birth weight 501 to 1500 g and gestational age </=34 weeks. Infants were randomized into 2 groups: \"slow\" (n = 98), who received 15 cc/kg/d increments (a 10-day schedule to full feeds) and \"fast\" (n = 87), who received 35 cc/kg/d increments (a 5-day schedule to full feeds) of Similac Special Care 20 cal/oz. Feeds were increased only if well tolerated as defined by a protocol.\n The incidence of NEC (Bell stage >/=II) was similar in both groups (slow 13% and fast 9%, P =.5). The incidence of perforation (Bell stage III) was also similar in both groups (slow 4% and fast 2%, P =.8). Feeds were started at a comparable postnatal age in both groups (median age: slow 5 days and fast 4 days, P =.9). Although the neonates in the fast group attained full enteral intake earlier (median days [25th and 75th percentiles]: slow 15 [12, 21] and fast 11 [8, 15], P <.001) and regained their birth weight earlier (slow 15 [11, 20] and fast 12 [8, 15], P <.05), their ages at discharge were not statistically different (slow 47 [31, 67] and fast 43 [29, 62], P =.3)\n A greater than twofold difference in the rate of feed advancement from 15 cc/kg/d to 35 cc/kg/d did not affect the incidence of NEC >/= stage II. Factors other than feed advancement appear to be more important in the pathogenesis or progression of NEC.", "To begin to determine the optimal time for initiating enteral feedings, 34 sick, very low birth weight infants were prospectively selected from all neonates of less than 1,500 g (N = 116) and randomly divided into two groups. Infants were fed either on day 1 (early) or 7 (late) of life, according to a feeding protocol which included parenteral nutrition and a scheduled progression from sterile water to 2.5% dextrose, half-strength, and finally full-strength formula over seven days. The incidence of necrotizing enterocolitis and subsequent hospital course were compared. Initiating enteral feedings on day 1 did not significantly increase the incidence of necrotizing enterocolitis, produce a clustering of cases, or induce an earlier onset of necrotizing enterocolitis. The overall incidence of necrotizing enterocolitis in sick, very low birth weight neonates was 29% (5/17) and 35% (6/17) in the early and late groups, respectively, compared with 4.2% (2/47) in minimally sick, very low birth weight neonates. No significant differences between groups were seen in obstetrical complications, birth weight, gestational age, Apgar scores, presence of patent ductus arteriosus or intraventricular hemorrhage, use of umbilical catheterization, and respiratory or oxygen requirements. Infants fed enterally from day 1 did show a significantly higher energy and protein intake during the second week of life. These data show that providing dilute, early enteral calories does not adversely affect the incidence of necrotizing enterocolitis." ]	The available trial data suggest that advancing enteral feed volumes at slow rather than faster rates does not reduce the risk of necrotising enterocolitis in very preterm or VLBW infants. Advancing the volume of enteral feeds at slow rates results in several days delay in regaining birth weight and establishing full enteral feeds but the long term clinical importance of these effects is unclear. The applicability of these findings to extremely preterm, extremely low birth weight or growth restricted infants is limited. Further randomised controlled trials in these populations may be warranted to resolve this uncertainty.
CD005212	[ "15774786", "18250350" ]	[ "Sequencing of chemotherapy and radiation therapy in early-stage breast cancer: updated results of a prospective randomized trial.", "Absolute risk reductions for local recurrence after postoperative radiotherapy after sector resection for ductal carcinoma in situ of the breast." ]	[ "The optimal integration of chemotherapy with radiation (RT) for patients with early-stage breast cancer remains uncertain. We present the long-term results of a prospective randomized trial to address this question.\n Two hundred forty-four patients were randomly assigned after conservative breast surgery to receive 12 weeks of cyclophosphamide, doxorubicin, methotrexate, fluorouracil, and prednisone (CAMFP) before RT (CT-first) or after RT (RT-first). Median follow-up for surviving patients was 135 months.\n There were no significant differences between the CT-first and RT-first arms in time to any event, distant metastasis, or death. Sites of first failure were also not significantly different.\n Among breast cancer patients treated with conservative surgery, there is no advantage to giving RT before adjuvant chemotherapy. However, this study does not have enough statistical power to rule out a clinically important survival benefit for either sequence.", "Evaluate the effects of radiotherapy after sector resection for ductal carcinoma in situ of the breast (DCIS) in patient groups as defined by age, size of the lesion, focality, completeness of excision and mode of detection.\n A total of 1,067 women in Sweden were randomly assigned to either postoperative radiotherapy (RT) or control from 1987 to 1999, and 1,046 were followed for a mean of 8 years. The main outcome was new ipsilateral breast cancer events and distant metastasis-free survival analyzed according to intention to treat.\n There were 64 ipsilateral events in the RT arm and 141 in the control group corresponding to a risk reduction of 16.0 percentage points at 10 years (95% CI, 10.3% to 21.6%) and a relative risk of 0.40 (95% CI, 0.30 to 0.54). There was no statistically significant difference in distant metastasis-free survival. There was an effect modification by age, yielding a low effect of RT in women younger than 50, but substantial protection in women older than 60 years. The age effect was not confounded by focality, lesion size, completeness of excision, or detection mode. There was no group as defined by our stratification variables that had a low risk without radiotherapy.\n Our results indicate that younger women have a low protective effect of conventional RT after sector resection. Older women benefit substantially. We caution that the age effect was seen in a subgroup analysis. Further search with conventional clinical variables for a low risk group that does not need RT does not seem fruitful." ]	The data included in this review, from three well-conducted randomised trials, suggest that different methods of sequencing CT and RT do not appear to have a major effect on recurrence or survival for women with breast cancer if RT is commenced within seven months after surgery.
CD003751	[ "17575560", "14710215", "12915605", "15858816", "18541641", "21825268", "9625213", "1350338", "21075644", "7677554", "10610626", "20219315", "18823177" ]	[ "Increasing oncologists' skills in eliciting and responding to emotional cues: evaluation of a communication skills training program.", "Effects of a 105 hours psychological training program on attitudes, communication skills and occupational stress in oncology: a randomised study.", "How to optimize physicians' communication skills in cancer care: results of a randomized study assessing the usefulness of posttraining consolidation workshops.", "Physicians' communication with a cancer patient and a relative: a randomized study assessing the efficacy of consolidation workshops.", "Effectiveness of a three-day communication skills course in changing nurses' communication skills with cancer/palliative care patients: a randomised controlled trial.", "Specific training program improves oncologists' palliative care communication skills in a randomized controlled trial.", "Improving communication skills--a randomized controlled behaviorally oriented intervention study for residents in internal medicine.", "Hypnosis or cognitive behavioral training for the reduction of pain and nausea during cancer treatment: a controlled clinical trial.", "Effects of communication skills training and a Question Prompt Sheet to improve communication with older cancer patients: a randomized controlled trial.", "Improving physicians' interviewing skills and reducing patients' emotional distress. A randomized clinical trial.", "Effect of clinician communication skills training on patient satisfaction. A randomized, controlled trial.", "A randomized controlled trial of communication training with primary care providers to improve patient-centeredness and health risk communication.", "Physician and patient communication training in primary care: effects on participation and satisfaction." ]	[ "Psychological morbidity in cancer patients is common, but often undetected and untreated. We developed a communication skills training (CST) program targeting this issue, and evaluated its impact on doctor behaviour.\n Thirty of 35 oncologists from six teaching hospitals in six Australian cities, participated. The CST was a 1.5-day intensive face-to-face workshop incorporating presentation of principles, a DVD modelling ideal behaviour and role-play practice, followed by four 1.5 h monthly video-conferences incorporating role-play of doctor-generated scenarios. Doctors were randomized to receive the CST or not. Simulated patient interviews were videotaped and coded at baseline, after CST and 6 months later. Doctors completed questionnaires assessing stress and burnout at the same time points.\n Doctors in the intervention group displayed more creating environment and fewer blocking behaviours at both follow-ups; however, these differences did not reach statistical significance. Intervention doctors valued the training highly, but did not report substantial reductions in stress and burnout.\n This short training programme demonstrated a positive effect on aspects of doctor behaviour. Video-conferencing after a short training course may be an effective strategy for delivering CST.\n (c) 2007 John Wiley & Sons, Ltd", "There is today a wide consensus regarding the need to improve communication skills (CS) of health-care professionals (HCPs) dealing with cancer patients. Psychological training programs (PTPs) may be useful to acquire the needed CS. Testing the efficacy of PTP will allow to define their optimal content. The present study was designed to assess the impact of a PTP on HCP stress, attitudes and CS, and on HCP and patients' satisfaction with HCP communication skills in a randomised study. A total of 115 oncology nurses were randomly assigned to a 105-h PTP or to a waiting list. Stress was assessed with the Nursing Stress Scale, attitudes with a Semantic Differential Questionnaire, CS used during one simulated and one actual patient interview with the Cancer Research Campaign Workshop Evaluation Manual, and satisfaction with the nurses' CS with a questionnaire completed by the patients and the nurses. Trained (TG) and control (CG) groups were compared at baseline, after 3 months (just following training for TG) and after 6 months (3 months after the end of training for TG). Compared to controls, trained nurses reported positive changes on their stress levels (P</=0.05) and on their attitudes (P</=0.05). Positive training effects were found on CS used during the simulated interview: a significant increase in facilitative behaviours (open questions: P</=0.001; evaluative functions: P</=0.05) and a significant decrease in inhibitory behaviours (inappropriate information: P</=0.01; false reassurance: P</=0.05). Less positive training effects were found regarding interviews with a cancer patient: a significant increase in educated guesses (P</=0.001) was noticed. No training effect was observed on nurses' satisfaction levels, but a positive training effect was found on patients' satisfaction levels (P</=0.01). Although results outline PTP efficacy, they indicate the need to design PTP, amplifying the transfer of learned CS to clinical practice.", "Although there is wide recognition of the usefulness of improving physicians' communication skills, no studies have yet assessed the efficacy of post-training consolidation workshops. This study aims to assess the efficacy of six 3-hour consolidation workshops conducted after a 2.5-day basic training program.\n Physicians, after attending the basic training program, were randomly assigned to consolidation workshops or to a waiting list. Training efficacy was assessed through simulated and actual patient interviews that were audiotaped at baseline and after consolidation workshops for the consolidation-workshop group, and approximately 5 months after the end of basic training for the waiting-list group. Communication skills were assessed according to the Cancer Research Campaign Workshop Evaluation Manual. Patients' perceptions of communication skills improvement were assessed using a 14-item questionnaire.\n Sixty-three physicians completed the training program. Communication skills improved significantly more in the consolidation-workshop group compared with the waiting-list group. In simulated interviews, group-by-time repeated measures analysis of variance showed a significant increase in open and open directive questions (P =.014) and utterances alerting patients to reality (P =.049), as well as a significant decrease in premature reassurance (P =.042). In actual patient interviews, results revealed a significant increase in acknowledgements (P =.022) and empathic statements (P =.009), in educated guesses (P =.041), and in negotiations (P =.008). Patients interacting with physicians who benefited from consolidation workshops reported higher scores concerning their physicians' understanding of their disease (P =.004).\n Consolidation workshops further improve a communication skills training program's efficacy and facilitate the transfer of acquired skills to clinical practice.", "Although patients with cancer are often accompanied by a relative during medical interviews, to the authors' knowledge little is known regarding the efficacy of communication skills training programs on physicians' communication skills in this context. The objective of the current study was to assess the efficacy of 6 consolidation workshops, 3 hours in length, that were conducted after a 2.5-day basic training program.\n After attending the basic training program, physicians were assigned randomly to consolidation workshops or to a waiting list. Training efficacy was assessed through simulated and actual interviews that were recorded on an audio tape at baseline, after consolidation workshops for the consolidation-workshops group, and 5 months after the end of basic training for the waiting-list group. Communication skills were assessed according to the Cancer Research Campaign Workshop Evaluation Manual. Patients' and relatives' perceptions of and satisfaction with physicians' communication performance were assessed using a 15-item questionnaire.\n Sixty-two physicians completed the training program. Compared with physicians who participated to the basic training program, when addressing the patient, physicians who were randomized to the consolidation workshops used more open, open directive, and screening questions (P = 0.011 in simulated patient interviews and P = 0.005 in actual patient interviews) and elicited and clarified psychologic concerns more often (P = 0.006 in simulated patient interviews and P < 0.001 in actual patient interviews). When they addressed the relative, physicians who were randomized to the consolidation workshops gave less premature information (P = 0.032 in simulated patient interviews and P < 0.001 in actual patient interviews). When they addressed the patient and the relative simultaneously, physicians who were randomized to the consolidation workshops used more empathy, educated guesses, alerting to reality, confronting, negotiating, and summarizing (P = 0.003 in simulated patient interviews and P = 0.024 in actual patient interviews). Patients, but not relatives, who interacted with physicians in the consolidation-workshops group were more satisfied globally with the interviews (P = 0.022).\n Six 3-hour consolidation workshops resulted in improved communication skills addressed to patients and to relatives. The current results showed that the transfer of skills addressing relatives' concerns remained limited and that consolidation workshops should focus even more systematically on the practice of three-person interviews.", "This multi-centre, two-armed parallel-group pragmatic randomised controlled trial (RCT) evaluated the effectiveness of a 3-day communication skills course in changing nurses' communication skills. The primary outcome was the change in the nurses' communication skills score from pre-course to 12 weeks post-course. The main secondary outcome was the change in the nurses' level of confidence in communicating with patients. A total of 172 nurses were randomised to the course or control. The communication skills score for the intervention group increased by 3.4 points post-course but decreased in the control by 0.05 points (between-group difference in change: 3.41, 95% CI: 2.16-4.66, P < 0.001). Confidence scores increased by 18.16 points for the intervention group but decreased 0.7 points in the control (between-group difference in change: 18.86, 95% CI: 13.39-24.34, P < 0.001). This RCT contributes to the evidence base on the effectiveness of communication skills training in cancer and palliative care.", "The aim of the study was to demonstrate that COM-ON-p, concise and individualized communication skills training (CST), improves oncologists' communication skills in consultations focusing on the transition to palliative care.\n Forty-one physicians were randomly assigned to a control (CG) or intervention group (IG). At t(0), all physicians held two video-recorded consultations with actor-patient pairs. Afterward, physicians in the IG participated in COM-ON-p. Five weeks after t(0), a second assessment took place (t(1)). COM-ON-p consists of an 11-hour workshop (1.5 days), pre- and postassessment (2 hours), and coaching (0.5 hours). Physicians focused on practicing individual learning goals with actor patients in small groups. To evaluate the training, blinded raters assessed communication behavior of the physicians in video-recorded actor-patient consultations using a specific checklist. Data were analyzed using a mixed model with baseline levels as covariates.\n Participants in the IG improved significantly more than those in the CG in all three sections of the COM-ON-Checklist: skills specific to the transition to palliative care, global communication skills, and involvement of significant others (all P < .01). Differences between the CG and IG on the global items of communication skills and involvement of significant others were also significant (P < .01). Effect sizes were medium to large, with a 0.5-point improvement on average on a five-point rating scale.\n Physicians can be trained to meet better core challenges during the transition to palliative care through developed concise CST. Generalization and transfer into clinical practice must be proven in additional studies.", "We investigated whether patient-centered communication skills can be taught to residents in Internal Medicine by using a time-limited behaviorally oriented intervention.\n Residents working at the Department of Internal Medicine were randomly assigned to an intervention group (IG; N = 19) or a control group (CG; N = 23). In addition to 6 hours of standard medical education per week, the IG received specific communication training of 22.5 hours duration within a 6-month period. Initially and 10 months later, participants performed interviews with simulated patients. Interviews were rated by blinded raters who used the Maastricht History and Advice Checklist-Revised.\n Compared with the CG, the IG improved substantially in many specific communication skills. Both groups improved in the \"amount of medical information identified\" and in the ability to \"communicate about feasibility of treatment.\"\n Patient-centered communication skills such as those presented in this intervention study can be taught. The ability to gain medical information and the readiness to communicate about aspects of medical treatment seem to improve with more professional experience; however, they also profit from the intervention.", "Few controlled clinical trials have tested the efficacy of psychological techniques for reducing cancer pain or post-chemotherapy nausea and emesis. In this study, 67 bone marrow transplant patients with hematological malignancies were randomly assigned to one of four groups prior to beginning transplantation conditioning: (1) hypnosis training (HYP); (2) cognitive behavioral coping skills training (CB); (3) therapist contact control (TC); or (4) treatment as usual (TAU; no treatment control). Patients completed measures of physical functioning (Sickness Impact Profile; SIP) and psychological functioning (Brief Symptom Inventory; BSI), which were used as covariates in the analyses. Biodemographic variables included gender, age and a risk variable based on diagnosis and number of remissions or relapses. Patients in the HYP, CB and TC groups met with a clinical psychologist for two pre-transplant training sessions and ten in-hospital \"booster\" sessions during the course of transplantation. Forty-five patients completed the study and provided all covariate data, and 80% of the time series outcome data. Analyses of the principal study variables indicated that hypnosis was effective in reducing reported oral pain for patients undergoing marrow transplantation. Risk, SIP, and BSI pre-transplant were found to be effective predictors of inpatient physical symptoms. Nausea, emesis and opioid use did not differ significantly between the treatment groups. The cognitive behavioral intervention, as applied in this study, was not effective in reducing the symptoms measured.", "A randomized pre- and post-test control group design was conducted in 12 oncology wards to investigate the effectiveness of an intervention, existing of a communication skills training with web-enabled video feedback and a Question Prompt Sheet (QPS), which aimed to improve patient education to older cancer patients (≥65 years). The effects were studied by analyzing questionnaires and video recordings of patient education sessions preceding chemotherapy with 210 different patients. Patients' recall of information was the primary outcome of the study. Recall was checked against the actual communication in the video-recordings. Moreover, communication skills were assessed by observing the extent to which nurses implemented 67 communication aspects, categorized in seven dimensions, using the QUOTE(chemo). Experimental nurses demonstrated a significant intervention effect on communicating realistic expectations. Within-group improvements were measured in the experimental group for tailored communication, affective communication and interpersonal communication. Although the use of a QPS significantly increased question asking, only limited results were found on older patients' recall scores. The overall proportion recall of recommendations showed a marginally significant pre-/post-change in proportion recall in favour of the experimental group and there was a significant pre-/post-change in two out of six sub-categories. The results indicate that nurses' communication skills can be improved by communication skills training. More research is needed to understand the difficult relationship between patient-provider communication and recall of information.\n Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.", "Despite high prevalence, emotional distress among primary care patients often goes unrecognized during routine medical encounters.\n To explore the effect of communication-skills training on the process and outcome of care associated with patients' emotional distress.\n A randomized, controlled field trial was conducted with 69 primary care physicians and 648 of their patients. Physicians were randomized to a no-training control group or one of two communication-skills training courses designed to help physicians address patients' emotional distress. The two training courses addressed communication through problem-defining skills or emotion-handling skills. All office visits of study physicians were audiotaped until five emotionally distressed and five nondistressed patients were enrolled based on patient response to the General Health Questionnaire. Physicians were also audiotaped interviewing a simulated patient to evaluate clinical proficiency. Telephone monitoring of distressed patients for utilization of medical services and General Health Questionnaire scores was conducted 2 weeks, 3 months, and 6 months after their audiotaped office visits.\n Audiotape analysis of actual and simulated patients showed that trained physicians used significantly more problem-defining and emotion-handling skills than did untrained physicians, without increasing the length of the visit. Trained physicians also reported more psychosocial problems, engaged in more strategies for managing emotional problems with actual patients, and scored higher in clinical proficiency with simulated patients. Patients of trained physicians reported reduction in emotional distress for as long as 6 months.\n Important changes in physicians' communication skills were evident after an 8-hour program. The training improved the process and outcome of care without lengthening the visits.", "Although substantial resources have been invested in communication skills training for clinicians, little research has been done to test the actual effect of such training on patient satisfaction.\n To determine whether clinicians' exposure to a widely used communication skills training program increased patient satisfaction with ambulatory medical care visits.\n Randomized, controlled trial.\n A not-for-profit group-model health maintenance organization in Portland, Oregon.\n 69 primary care physicians, surgeons, medical subspecialists, physician assistants, and nurse practitioners from the Permanente Medical Group of the Northwest.\n \"Thriving in a Busy Practice: Physician-Patient Communication,\" a communication skills training program consisting of two 4-hour interactive workshops. Between workshops, participants audiotaped office visits and studied the audiotapes.\n Change in mean overall score on the Art of Medicine survey (HealthCare Research, Inc., Denver, Colorado), which measures patients' satisfaction with clinicians' communication behaviors, and global visit satisfaction.\n Although participating clinicians' self-reported ratings of their communication skills moderately improved, communication skills training did not improve patient satisfaction scores. The mean score on the Art of Medicine survey improved more in the control group (0.072 [95% CI, -0.010 to 0.154]) than in the intervention group (0.030 [CI, -0.060 to 0.1201).\n \"Thriving in a Busy Practice: Physician-Patient Communication,\" a typical continuing medical education program geared toward developing clinicians' communication skills, is not effective in improving general patient satisfaction. To improve global visit satisfaction, communication skills training programs may need to be longer and more intensive, teach a broader range of skills, and provide ongoing performance feedback.", "to determine the efficacy and effectiveness of training to improve primary care providers' patient-centered communication skills and proficiency in discussing their patients' health risks.\n twenty-eight primary care providers participated in a baseline simulated patient interaction and were subsequently randomized into intervention and control groups. Intervention providers participated in training focused on patient-centered communication about behavioral risk factors. Immediate efficacy of training was evaluated by comparing the two groups. Over the next 3 years, all providers participated in two more sets of interactions with patients. Longer term effectiveness was assessed using the interaction data collected at 6 and 18 months post-training.\n The intervention providers significantly improved in patient-centered communication and communication proficiencies immediately post-training and at both follow-up time points.\n this study suggests that the brief training produced significant and large differences in the intervention group providers which persisted 2 years after the training.\n the results of this study suggest that primary care providers can be trained to achieve and maintain gains in patient-centered communication, communication skills and discussion of adverse childhood events as root causes of chronic disease.\n 2010 Elsevier Ireland Ltd. All rights reserved.", "To assess the effects of a communication skills training program for physicians and patients.\n A randomized experiment to improve physician communication skills was assessed 1 and 6 months after a training intervention; patient training to be active participants was assessed after 1 month. Across three primary medical care settings, 156 physicians treating 2,196 patients were randomly assigned to control group or one of three conditions (physician, patient, or both trained).\n Patient satisfaction and perceptions of choice, decision-making, information, and lifestyle counseling; physicians' satisfaction and stress; and global ratings of the communication process.\n The following significant (p < .05) effects emerged: physician training improved patients' satisfaction with information and overall care; increased willingness to recommend the physician; increased physicians' counseling (as reported by patients) about weight loss, exercise, and quitting smoking and alcohol; increased physician satisfaction with physical exam detail; increased independent ratings of physicians' sensitive, connected communication with their patients, and decreased physician satisfaction with interpersonal aspects of professional life. Patient training improved physicians' satisfaction with data collection; if only physician or patient was trained, physician stress increased and physician satisfaction decreased.\n Implications for improving physician-patient relationship outcomes through communication skills training are discussed.\n PsycINFO Database Record (c) 2008 APA, all rights reserved." ]	Various CST courses appear to be effective in improving some types of HCP communication skills related to information gathering and supportive skills. We were unable to determine whether the effects of CST are sustained over time, whether consolidation sessions are necessary, and which types of CST programs are most likely to work. We found no evidence to support a beneficial effect of CST on HCP 'burnout', patients' mental or physical health, and patient satisfaction.
CD007270	[ "16177249", "20402591" ]	[ "Single-dose azithromycin versus penicillin G benzathine for the treatment of early syphilis.", "A phase III equivalence trial of azithromycin versus benzathine penicillin for treatment of early syphilis." ]	[ "Pilot studies suggest that a single, 2-g oral dose of azithromycin may be an alternative to a 2.4-MU intramuscular dose of penicillin G benzathine in the prevention and treatment of syphilis. We evaluated the efficacy of treatment with azithromycin in a developing country.\n A total of 328 subjects, 25 with primary and 303 with high-titer (a titer of at least 1:8 on a rapid plasmin reagin [RPR] test) latent syphilis, were recruited through screening of high-risk populations in Mbeya, Tanzania, and randomly assigned to receive 2 g of azithromycin orally (163 subjects) or 2.4 million units of penicillin G benzathine intramuscularly (165 subjects). The primary outcome was treatment efficacy, with cure defined serologically (a decline in the RPR titer of at least two dilutions by nine months after treatment) and, in primary syphilis, by epithelialization of ulcers within one or two weeks.\n The average age of participants was 27.0 years, 235 (71.6 percent) were female, and 171 (52.1 percent) were seropositive for human immunodeficiency virus. Cure rates were 97.7 percent (95 percent confidence interval, 94.0 to 99.4) in the azithromycin group and 95.0 percent (95 percent confidence interval, 90.6 to 97.8) in the penicillin G benzathine group (95 percent confidence interval for the difference, -1.7 to 7.1 percent), achieving prespecified criteria for equivalence. Cure rates were also similar three and six months after treatment in the two groups and in all subgroups. Cure rates at three months were 59.4 percent (95 percent confidence interval, 51.8 to 67.1) in the azithromycin group and 59.5 percent (95 percent confidence interval, 51.8 to 67.3) in the penicillin G benzathine group and at six months were 85.5 percent (95 percent confidence interval, 79.4 to 90.6) and 81.5 percent (95 percent confidence interval, 74.8 to 87.4), respectively.\n Single-dose oral azithromycin is effective in treating syphilis and may be particularly useful in developing countries in which the use of penicillin G benzathine injections is problematic. However, recent reports of azithromycin-resistant Treponema pallidum in the United States indicate the importance of continued monitoring for resistance.\n Copyright 2005 Massachusetts Medical Society.", "Syphilis remains an important source of morbidity worldwide. Long-acting penicillin is the only therapy currently recommended for syphilis in much of the world. Because of hesitation to use penicillin for fear of anaphylaxis, there is a need for an effective, well-tolerated alternative to penicillin for syphilis therapy.\n This multicenter, randomized clinical trial was conducted in clinics for the treatment of persons with sexually transmitted diseases. We compared serological cure rates for human immunodeficiency virus (HIV)-negative persons with early syphilis treated with azithromycin at a dosage of 2.0 g administered orally as a single dose with cure rates for those treated with benzathine penicillin G at a dosage of 2.4 million units administered intramuscularly.\n A total of 517 participants were enrolled in the trial. In the intention-to-treat analysis, after 6 months of follow-up, serological cure was observed in 180 (77.6%) of 232 azithromycin recipients and 186 (78.5%) of 237 penicillin recipients (1-sided lower bound 95% confidence interval, 7.2%). Nonserious adverse events were more common among azithromycin recipients than they were among penicillin recipients (61.5% vs 46.3%), and such adverse events were accounted for, in large part, by self-limited gastrointestinal complaints.\n In this trial, the efficacy of azithromycin at a dosage of 2.0 g administered orally was equivalent to that of benzathine penicillin G for the treatment of early syphilis in persons without HIV infection." ]	Differences in the odds of cure did not reach statistical significance when azithromycin was compared with benzathine penicillin for the treatment of early syphilis. No definitive conclusion can be made regarding the relative safety of benzathine penicillin G and azithromycin for early syphilis. Further studies on the utility of benzathine penicillin G for early syphilis are warranted.
CD005199	[ "8307216", "12791021", "15674491", "19474689", "6351265", "19259615", "15449205", "20075532", "9842825", "8443666", "1461854", "20547822", "11684971", "6988034" ]	[ "The comparison of type of incision for transperitoneal abdominal aortic surgery based on postoperative respiratory complications and morbidity.", "Midline or transverse abdominal incision for right-sided colon cancer-a randomized trial.", "Transverse versus midline incision for upper abdominal surgery.", "Midline versus transverse incision in major abdominal surgery: a randomized, double-blind equivalence trial (POVATI: ISRCTN60734227).", "Abdominal incisions: transverse vs vertical placement and continuous vs interrupted closure.", "Incisional hernia after upper abdominal surgery: a randomised controlled trial of midline versus transverse incision.", "Prospective randomized study of two laparotomy incisions for gastrectomy: midline incision versus transverse incision.", "Thoracic epidural analgesia in obese patients with body mass index of more than 30 kg/m2 for off pump coronary artery bypass surgery.", "Postoperative analgesia with intramuscular morphine at fixed rate versus epidural morphine or sufentanil and bupivacaine in patients undergoing major abdominal surgery.", "Comparative study of abdominal incision techniques.", "Patient recovery following cholecystectomy through a 6 cm or 15 cm transverse subcostal incision: a prospective randomized clinical trial.", "Transversus abdominis plane block does not provide additional benefit to multimodal analgesia in gynecological cancer surgery.", "Double-masked randomized trial comparing alternate combinations of intraoperative anesthesia and postoperative analgesia in abdominal aortic surgery.", "Midline or transverse laparotomy? A random controlled clinical trial. Part II: Influence on postoperative pulmonary complications." ]	[ "Equal access to the abdominal aorta can be attained through midline and transverse abdominal incisions. The surgical literature suggests that transverse incisions cause less postoperative pain and morbidity. Fifty patients (10 females and 40 males, mean age 67 years) undergoing abdominal aortic surgery were randomised to a midline (n = 25) or transverse (n = 25) incision. All patients were evaluated preoperatively and postoperatively for seven days. Changes in pulmonary function (FVC and FEV1), time to open and close the incision, analgesia used (morphine mg/kg/h), clinical or X-ray evidence of chest infection, and the duration of ICU stay were recorded. In the transverse group there was a reduction in the incidence of chest complications (20% vs. 28%, p = ns) and these incisions took longer to open (13.9 +/- 4.6 vs. 9.9 +/- 5.1, p < 0.05), but overall there was no significant difference between any other parameter in the two groups. Our results show no statistically significant difference in morbidity or analgesia consumption following transverse or midline abdominal incisions and we conclude that the type of incision used can be left to the surgeon's preference.", "The influence of the type of abdominal incision on post-operative pain and pulmonary function was investigated in patients operated upon for a right-sided cancer of the large bowel.\n Fifty-three patients scheduled for a right hemicolectomy due to a right-sided colon cancer were randomized to a median vertical (M) or a transverse incision (T). Forty patients, 23 with a M and 17 with a T incision, completed the study and could be evaluated. Pain at rest and after physical activity was assessed with a visual analogue scale, and was also measured as reflected in the need for analgesics. Respiratory function was assessed with pre- and post-operative spirometry.\n Pain after activity was significantly less in patients with a T incision. This group also needed less analgesia. Vital capacity (VC) and forced expiratory volume in 1 s (FEV 1.0) were profoundly reduced after surgery in both groups of patients, but improvement of respiratory function was faster in patients with a transverse incision. No problem with access to the operative field was noted.\n We conclude that a transverse incision is preferable to a midline incision and should be used in right hemicolectomy. This abdominal incision reduces effort-induced pain and interferes less with post-operative pulmonary function, and may reduce the risk of pulmonary complications.", "Transverse and midline abdominal incisions are both commonly used for laparotomy to perform surgery on the pancreas and stomach, but comparative data are limited, especially from prospective randomized trials.\n During a predefined 2-year recruitment period, 94 patients undergoing an elective major laparotomy for disorders of the pancreas or stomach were enrolled in this study. The outcome measures were pulmonary function, incisional pain, and wound characteristics.\n The operation groups were equally divided according to the type of incision used. The patients who underwent transverse incision laparotomy had significantly better postoperative pulmonary function and significantly less postoperative incisional pain than those who underwent midline incision laparotomy (P < 0.05), but there were no differences in morbidity and the incidence of wound complications.\n Performing a transverse incision for surgery on the pancreas or stomach results in better postoperative pulmonary function and less incisional pain than a midline incision, without affecting postoperative morbidity.", "There are 2 main types of access for patients requiring major open, elective abdominal surgery: the midline or the transverse approach. The aim of this study is to compare both approaches by focusing on postoperative pain, complications, and frequency of incisional hernias.\n A recent Cochrane review suggested that transverse incisions may be less painful but incisional hernia rates do not differ.\n Randomized, patient- and observer-blinded, monocentric, equivalence clinical trial. Patients were scheduled for elective primary abdominal incisions. Composite primary end point measured 48 hours after surgery was the total amount of analgesics (piritramide) required in the last 24 hours and pain (Visual Analogue Scale). Secondary end points were early-onset and late complications. This study is registered in the ISRCTN registry and has the ID number ISRCTN60734227.\n Two hundred patients (101 midline and 99 transverse) were randomized. Both incision types resulted in similar amounts of required analgesics (95% confidence interval [-0.38; -0.33] was included in the equivalence level). For the Visual Analogue Scale, both the 95% and 90% CI (0-10) were neither within the equivalence levels nor were their differences significant at the 5% level. No relevant differences between midline and transverse incisions were observed for 30-day mortality (2 vs. 2, P = 0.99), mortality after one year (15 vs. 23, P = 0.15), pulmonary complications (13 vs. 17, P = 0.43), median length of hospital stay (11 vs. 12 days, P = 0.08), median time to tolerance of solid food (12 vs. 14 days, P = 0.30), and incisional hernias after one year (13 vs. 8, P = 0.48). More wound infections occurred in the transverse group (15 vs. 5, P = 0.02).\n The decision about the incision should be driven by surgeon preference with respect to the patient's disease and anatomy.", "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 determine whether a transverse incision is an alternative to a midline incision in terms of incisional hernia incidence, surgical site infection, postoperative pain, hospital stay and cosmetics in cholecystectomy. Incisional hernias after midline incision are commonly underestimated but probably complicate between 2 and 20% of all abdominal wall closures. The midline incision is the preferred incision for surgery of the upper abdomen despite evidence that alternatives, such as the lateral paramedian and transverse incision, exist and might reduce the rate of incisional hernia. A RCT was preformed in the pre-laparoscopic cholecystectomy era the data of which were never published.\n One hundred and fifty female patients were randomly allocated to cholecystectomy through midline or transverse incision. Early complications, the duration to discharge and the in-hospital use of analgesics was noted. Patients returned to the surgical outpatient clinic for evaluation of the cosmetic results of the scar and to evaluate possible complications such as fistula, wound dehiscence and incisional hernia after a minimum of 12 months follow-up.\n Two percent (1/60) of patients that had undergone the procedure through a transverse incision presented with an incisional hernia as opposed to 14% (9/63) of patients from the midline incision group (P = 0.017). Transverse incisions were found to be significantly shorter than midline incisions and associated with more pleasing appearance. More patients having undergone a midline incision, reported pain on day one, two and three postoperatively than patients from the transverse group. The use of analgesics did not differ between the two groups.\n In light of our results a transverse incision should, if possible, be considered as the preferred incision in acute and elective surgery of the upper abdomen when laparoscopic surgery is not an option.", "We performed a randomized study to evaluate the differences between upper midline incision and transverse incision for gastrectomy.\n Patients undergoing distal gastrectomy or total gastrectomy for gastric cancer were randomly allocated to have either an upper midline incision or a transverse incision. The times taken to open and close the abdominal cavity, the number of doses of postoperative analgesics, and the incidence of postoperative pneumonia, wound infection, and intestinal obstruction were compared between the patients having the two incisions.\n Times for both opening and closing the abdominal cavity were longer with a transverse incision, in both the distal gastrectomy group and total gastrectomy group. In the patients in whom continuous epidural analgesia was used postoperatively, the number of additional doses of analgesics was smaller in the transverse-incision group after distal gastrectomy. The incidence of postoperative pneumonia was lower in the transverse-incision group after distal gastrectomy. The number of patients with postoperative intestinal obstruction was smaller in the transverse-incision group than in the midline-incision group after distal gastrectomy. In contrast to distal gastrectomy, there was no significant difference in the number of doses of postoperative analgesics, incidence of postoperative pneumonia, or incidence of postoperative intestinal obstruction between the two study groups after total gastrectomy.\n A transverse incision for distal gastrectomy may be more beneficial than an upper midline incision in attenuating postoperative wound pain, decreasing the incidence of postoperative pneumonia, and preventing postoperative intestinal obstruction.", "Perioperative Thoracic epidural analgesia (TEA) is an important part of a multimodal approach to improve analgesia and patient outcome after cardiac and thoracic surgery. This is particularly important for obese patients undergoing off pump coronary artery bypass surgery (OPCAB). We conducted a randomized clinical trial at tertiary care cardiac institute to compare the effect of TEA and conventional opioid based analgesia on perioperative lung functions and pain scores in obese patients undergoing OPCAB. Sixty obese patients with body mass index >30 kg/m2 for elective OPCAB were randomized into two groups (n=30 each). Patients in both the groups received general anesthesia but in group 1, TEA was also administered. We performed spirometry as preoperative assessment and at six hours, 24 hours, second, third, fourth and fifth day after extubation, along with arterial blood gases analysis. Visual analogue scale at rest and on coughing was recorded to assess the degree of analgesia. The other parameters observed were: time to endotracheal extubation, oxygen withdrawal time and intensive care unit length of stay. On statistical analysis there was a significant difference in Vital Capacity at six hours, 24 hours, second and third day postextubation. Forced vital capacity and forced expiratory volume in one second followed the same pattern for first four postoperative days and peak expiratory flow rate remained statistically high till second postoperative day. ABG values and PaO2/FiO2 ratio were statistically higher in the study group up to five days. Visual analogue scale at rest and on coughing was significantly lower till fourth and third postoperative day respectively. Tracheal extubation time, oxygen withdrawal time and ICU stay were significantly less in group 1. The use of TEA resulted in better analgesia, early tracheal extubation and shorter ICU stay and should be considered for obese patients undergoing OPCAB.", "We assessed the efficacy and side effects of postoperative analgesia with three different pain regimens in 90 patients undergoing major abdominal surgery. The patients were randomly assigned to one of three groups: epidural morphine (EM) or sufentanil (ES), both combined with bupivacaine, or IM morphine (IM) at fixed intervals. Before incision, patients in the epidural groups received sufentanil or morphine in bupivacaine via a thoracic catheter, followed by a continuous infusion 1 h later. General anesthesia consisted of N2O/O2 and isoflurane for all groups. Patients in all groups received IV sufentanil as part of their anesthetic management. Patients in the IM group received IV sufentanil 1 microg/kg before incision, and patients in all groups received sufentanil 10 microg for inadequate analgesia. Postoperatively, the epidural or IM treatment was continued for > or =5 days. Postoperative analgesia at rest and during coughing and movement was significantly better in the epidural groups than in the IM group during the 5 consecutive days. There were no significant differences between the epidural groups. The incidence of most side effects was similar in all groups. We conclude that epidural analgesia provided better pain relief than IM analgesia, even if the latter was optimized by fixed-dose administration at fixed intervals and included adjustments on demand. Epidural sufentanil and morphine, both combined with bupivacaine, seemed to be equally effective with similar side effects.\n Postoperative analgesia with epidural sufentanil or morphine and bupivacaine after major abdominal surgery seemed to be better than the conventional method of IM morphine treatment, despite optimal administration, i.e., fixed doses at fixed intervals with regular adjustments. Analgesic efficacy and side effects of epidural sufentanil and morphine were similar.", "The characteristics of surgical incisions made with an electrosurgical technique were compared with those made using conventional methods in a prospective randomized trial. In particular, the claim that the method of incision may influence postoperative pain was investigated. A total of 101 consecutive patients receiving full-length midline laparotomy incisions for gastrointestinal resection were studied. A record was kept of the time required to make the incision and blood loss as well as postoperative pain (using a linear analogue scale), ventilatory function and requirement for analgesia. There were 50 patients in group 1 (scalpel; 15 men, 35 women) and 51 in group 2 (electrocautery; 26 men, 25 women). The groups were similar in age, body-weight, diagnosis and the type of surgical procedures being performed. Incision time was similar in the two groups but median blood loss during incision was significantly less in group 2 patients than in group 1 (10 versus 25 ml, P < 0.0001). Linear analogue pain scores were not significantly different between the groups at any stage after operation. The same was true of postoperative ventilatory function and requirement for analgesia. A total value for morphine use during the entire postoperative period was derived for each group and the median was 1.55 mg/kg for group 1 compared with 1.49 mg/kg for group 2. The electrosurgical method is associated with less blood loss during incision, although this study has failed to confirm any reduction in postoperative pain or requirement for analgesia in these patients.", "The effect of incision length on patient recovery following cholecystectomy has not been investigated previously. In this study, 30 patients with symptomatic gallstones were randomized to cholecystectomy through a 6 cm or 15 cm transverse subcostal incision. Postoperative hospital stay was significantly shorter in the 6 cm incision group (median 3 days vs 5 days; P = 0.0069 Mann-Whitney U-test). In the 6 cm group analgesic requirements were reduced (median 2.5 vs 4.5 intramuscular opiate injections per patient) and recovery of depressed postoperative pulmonary function (FVC and FEV1) was faster (3% difference between groups on day 1 and 7% on day 3), although these differences did not achieve statistical significance. These results suggest that the length of incision may influence patient recovery following elective cholecystectomy. This has important implications as surgery carried out through shorter and less traumatic incisions may offer a cost-effective alternative to laparoscopic cholecystectomy. Moreover, some surgeons may find mini-laparotomy cholecystectomy easier to adopt than laparoscopic techniques.", "The transversus abdominis plane (TAP) block is a recently described technique involving injecting local anesthetic between the internal oblique and transversus abdominis layers of the abdominal wall. It has been shown to be effective in reducing morphine consumption and improving postoperative pain relief in several clinical settings.\n We performed a randomized placebo-controlled trial comparing bilateral ultrasound-guided TAP blocks (2 x 20 mL 0.5% ropivacaine or 0.9% saline) in adult female patients undergoing midline laparotomy for known or presumed gynecological malignancy. Both groups received multimodal IV analgesia. The primary outcomes for the study were defined as the incidence of \"inadequate\" analgesia (defined as a score >50 mm on a visual analog scale) with forced expiration at 2 hours postoperatively and total postoperative morphine consumption at 2 hours and 24 hours.\n Data from 65 patients were included in the study. The groups were comparable in terms of age, weight, surgical duration, and intraoperative morphine doses. There were no significant differences between the control and treatment groups in the proportion of patients with inadequate analgesia either at rest (39% vs. 22%, P = 0.13) or with coughing (61% vs. 53%, P = 0.54) at 2 hours. There was no significant difference in postoperative morphine consumption between the placebo and treatment groups at 2 hours (13.5 mg vs. 11.87 mg, P = 0.53) or 24 hours (34.0 mg vs. 36.1 mg, P = 0.76). There were no significant differences in the incidence of opioid side effects or patient satisfaction.\n This study demonstrated that TAP blockade conferred no benefit in addition to multimodal analgesia in women undergoing major gynecological cancer surgery.", "Improvement in patient outcome and reduced use of medical resources may result from using epidural anesthesia and analgesia as compared with general anesthesia and intravenous opioids, although the relative importance of intraoperative versus postoperative technique has not been studied. This prospective, double-masked, randomized clinical trial was designed to compare alternate combinations of intraoperative anesthesia and postoperative analgesia with respect to postoperative outcomes in patients undergoing surgery of the abdominal aorta.\n One hundred sixty-eight patients undergoing surgery of the abdominal aorta were randomly assigned to receive either thoracic epidural anesthesia combined with a light general anesthesia or general anesthesia alone intraoperatively and either intravenous or epidural patient-controlled analgesia postoperatively (four treatment groups). Patient-controlled analgesia was continued for at least 72 h. Protocols were used to standardize perioperative medical management and to preserve masking intraoperatively and postoperatively. A uniform surveillance strategy was used for the identification of prospectively defined postoperative complications. Outcome evaluation included postoperative hospital length of stay, direct medical costs, selected postoperative morbidities, and postoperative recovery milestones.\n Length of stay and direct medical costs for patients surviving to discharge were similar among the four treatment groups. Postoperative outcomes were similar among the four treatment groups with respect to death, myocardial infarction, myocardial ischemia, reoperation, pneumonia, and renal failure. Epidural patient-controlled analgesia was associated with a significantly shorter time to extubation (P = 0.002). Times to intensive care unit discharge, ward admission, first bowel sounds, first flatus, tolerating clear liquids, tolerating regular diet, and independent ambulation were similar among the four treatment groups. Postoperative pain scores were also similar among the four treatment groups.\n In patients undergoing surgery of the abdominal aorta, thoracic epidural anesthesia combined with a light general anesthesia and followed by either intravenous or epidural patient-controlled analgesia, offers no major advantage or disadvantage when compared with general anesthesia alone followed by either intravenous or epidural patient-controlled analgesia.", "In a series of 579 patients undergoing major laparotomy, the direction of incision (midline or transverse/oblique muscle-cutting) was decided randomly. The severity of postoperative pulmonary complications was expressed by a scoring system which allowed categorization into mild (score 0-3), moderate (score 4-6) and serious (score 7 or more) complications. The important determinants of high scores were found to be male sex, preoperative pulmonary dysfunction, postoperative ventilatory depression, hypovolaemic and septic shock, inhalation of gastric contents and embolism. In no stratum did the direction of incision have any significant effect." ]	The analgesia use and the pulmonary compromise may be reduced with a transverse/oblique incision but this does not seem to be significant clinically as pulmonary complication rates and recovery times were the same. The likelihood of wound dehiscence and rupture appears to be reduced with a transverse incision and a transverse incision may look better. The methodological and clinical diversity and the potential for bias also mean that the results in favour of a transverse/oblique incision (particularly with regard to analgesic use) should be treated with caution. The optimal incision for abdominal surgery still remains the preference of the surgeon.
CD002748	[ "12100834", "15795415", "11182394", "8182811", "8096941", "19042837", "19276838", "12035205", "12359854", "10833696", "19242918", "18490891", "10522767", "17307761", "21689848", "10607980", "15171968", "9135895", "9885092", "7707420", "18955452", "7059922", "11918907", "16802254", "17661342", "17602076", "19759996", "15378098", "15022300", "16046894", "15519257", "11483325", "16374892", "12721239", "10474848" ]	[ "The efficacy of a mind-body-spirit group for women with breast cancer: a randomized controlled trial.", "Efficacy of prophylactic mastectomy in women with unilateral breast cancer: a cancer research network project.", "Contralateral prophylactic mastectomy improves the outcome of selected patients undergoing mastectomy for breast cancer.", "Impact of follow-up testing on survival and health-related quality of life in breast cancer patients. A multicenter randomized controlled trial. The GIVIO Investigators.", "Breast cancer screening with mammography: overview of Swedish randomised trials.", "A pilot phase II randomized, cross-over, double-blinded, controlled efficacy study of octreotide versus hyoscine hydrobromide for control of noisy breathing at the end-of-life.", "A randomized trial to increase physical activity in breast cancer survivors.", "Counseling women with breast cancer using principles developed by Albert Bandura.", "Randomized trial of breast self-examination in Shanghai: final results.", "Telephone therapy for patients with breast cancer.", "Exercise and quality of life during and after treatment for breast cancer: results of two randomized controlled trials.", "A brief intervention for fatigue management in breast cancer survivors.", "Effects of a nursing intervention on subjective distress, side effects and quality of life of breast cancer patients receiving curative radiation therapy--a randomized study.", "Benefits of supervised group exercise programme for women being treated for early stage breast cancer: pragmatic randomised controlled trial.", "A randomised controlled trial testing the feasibility and efficacy of a physical activity behavioural change intervention in managing fatigue with gynaecological cancer survivors.", "Effects of group CBT on the survival time of patients with metastatic breast cancer.", "Nurse-led follow-up on demand or by a physician after breast cancer surgery: a randomised study.", "Thirty years of Medical Research Council randomized trials in solid tumours.", "A randomized controlled trial of the effects of group psychological therapy on survival in women with metastatic breast cancer.", "Effects of individualized breast cancer risk counseling: a randomized trial.", "Evolution of the randomized controlled trial in oncology over three decades.", "Effects of counseling for late stage cancer patients.", "Long-term effects of mammography screening: updated overview of the Swedish randomised trials.", "Combined aerobic and resistance training in breast cancer survivors: A randomized, controlled pilot trial.", "A randomized controlled trial to evaluate the effectiveness of a brief, behaviorally oriented intervention for cancer-related fatigue.", "Main outcomes of the FRESH START trial: a sequentially tailored, diet and exercise mailed print intervention among breast and prostate cancer survivors.", "Home-based exercise to alleviate fatigue and improve functional capacity among breast cancer survivors.", "The effect of seated exercise on fatigue and quality of life in women with advanced breast cancer.", "A randomized clinical trial of energy conservation for patients with cancer-related fatigue.", "Dance and movement program improves quality-of-life measures in breast cancer survivors.", "Closed loop stimulation in prevention of vasovagal syncope. Inotropy Controlled Pacing in Vasovagal Syncope (INVASY): a multicentre randomized, single blind, controlled study.", "Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy--results of a multicentric randomized German trial in advanced head-and-neck cancer.", "A pilot study of yoga for breast cancer survivors: physical and psychological benefits.", "Randomized controlled trial of exercise training in postmenopausal breast cancer survivors: cardiopulmonary and quality of life outcomes.", "A group cognitive behaviour therapy programme with metastatic breast cancer patients." ]	[ "Increasing numbers of women with breast cancer are seeking alternatives to standard group support in coping with their illness. This study examines outcomes for 181 women with breast cancer randomized to either a 12-week standard group support or a 12-week complementary and alternative medicine (CAM) support intervention. Participants in the CAM group were taught the use of meditation, affirmation, imagery and ritual. The standard group combined cognitive-behavioral approaches with group sharing and support. Both interventions were found to be associated with improved quality of life (CAM, P=0.008; Standard, P=0.006), decreased depression (CAM, P=0.004; Standard, P=0.02), decreased anxiety (CAM, P=0.0003; Standard, P=0.02) and increased \"spiritual well-being\" (CAM, P=002; Standard, P=0.003). Only the CAM group showed increases in measures of Spiritual Integration (P=0.001) which were also significant between groups (P=0.003). The Standard group was associated with decreased confusion (P=0.01) and decreased helplessness/hopelessness (P=0.01), while the CAM group was associated with decreased avoidance (P=0.01). None of these latter changes were significant between groups. At baseline, very high correlations were noted between measures of quality of life, mood, and spiritual integration. At the end of the intervention, the CAM group showed higher satisfaction (P=0.006) and fewer dropouts (P=0.006) compared to the standard group. Better outcomes in quality of life in the CAM group were associated with lower initial fighting spirit (r=-.39, P=0.001). No baseline factors predicted better outcomes in the Standard group. In summary, the study found equivalence on most psychosocial outcomes between the two interventions.", "We investigated the efficacy of contralateral prophylactic mastectomy (CPM) in reducing contralateral breast cancer incidence and breast cancer mortality among women who have already been diagnosed with breast cancer.\n This retrospective cohort study comprised approximately 50,000 women who were diagnosed with unilateral breast cancer during 1979 to 1999. Using computerized data confirmed by chart review, we identified 1,072 women (1.9%) who had CPM. We obtained covariate information for these women and for a sample of 317 women who did not undergo CPM.\n The median time from initial breast cancer diagnosis to the end of follow-up was 5.7 years. Contralateral breast cancer developed in 0.5% of women with CPM, metastatic disease developed in 10.5%, and subsequent breast cancer developed in 12.4%; 8.1% died from breast cancer. Contralateral breast cancer developed in 2.7% of women without CPM, and 11.7% died of breast cancer. After adjustment for initial breast cancer characteristics, treatment, and breast cancer risk factors, the hazard ratio (HR) for the occurrence of contralateral breast cancer after CPM was 0.03 (95% CI, 0.006 to 0.13). After adjustment for breast cancer characteristics and treatment, the HRs for the relationship of CPM with death from breast cancer, with death from other causes, and with all-cause mortality were 0.57 (95% CI, 0.45 to 0.72), 0.78 (95% CI, 0.57 to 1.06), and 0.60 (95% CI, 0.50 to 0.72), respectively.\n CPM seems to protect against the development of contralateral breast cancer, and although women who underwent CPM had relatively low all-cause mortality, CPM also was associated with decreased breast cancer mortality.", "Risk factors for contralateral breast cancer (CBC) may indicate a benefit for contralateral prophylactic mastectomy (CPM) at the time of unilateral mastectomy for breast cancer. The purpose of this study is to evaluate the efficacy of CPM in preventing CBC.\n sixty-four patients undergoing CPM and a control group of 182 patients not undergoing CPM and matched for age, stage, surgery, chemotherapy, and hormonal therapy were retrospectively compared for CBC rate, disease-free survival, and overall survival.\n Thirty-six CBCs occurred in the control group. In the CPM group, 3 CBCs were found at the time of prophylactic mastectomy, but none occurred subsequently (P = 0.005). Disease-free survival at 15 years in the CPM group was 55% (95% confidence interval [CI] 38% to 69%) versus 28% (95% CI 19% to 36%) in the control group (P = 0.01). Overall survival at 15 years was 64% (95% CI 45% to 78%) CPM versus 48% (95% CI 39% to 58%) in controls (P = 0.26).\n CPM prevented CBC and significantly prolonged disease-free survival. Future studies will need to address risk assessment and contralateral breast cancer prevention in patients treated for early breast cancer.", "To assess prospectively the impact on survival and health-related quality of life of two follow-up protocols in patients with early breast cancer.\n Randomized controlled clinical trial.\n Multicenter study involving 26 general hospitals in Italy.\n A consecutive sample of 1320 women younger than 70 years with stage I, II, and III unilateral primary breast cancer.\n Patients were randomly assigned to an intensive surveillance, which included physician visits and performance of bone scan, liver echography, chest roentgenography, and laboratory tests at predefined intervals (n = 655), or to a control regimen (n = 665), in which patients were seen by their physicians at the same frequency but only clinically indicated tests were performed. Both groups received a yearly mammogram aimed at detecting contralateral breast cancer.\n Primary end points were overall survival and health-related quality of life.\n Compliance to the two follow-up protocols was more than 80%. At a median follow-up of 71 months, no difference was apparent in overall survival with 132 deaths (20%) in the intensive group and 122 deaths (18%) in the control group. No significant differences were apparent in time to detection of recurrence between the two groups. Measurements of health-related quality of life (ie, overall health and quality-of-life perception, emotional well-being, body image, social functioning, symptoms, and satisfaction with care) at 6, 12, 24, and 60 months of follow-up did not show differences by type of care received.\n Results of this trial support the view that a protocol of frequent laboratory tests and roentgenography after primary treatment for breast cancer does not improve survival or influence health-related quality of life. Routine use of these tests should be discouraged.", "Despite encouraging results from screening trials the efficacy of mammography in reducing mortality remains somewhat controversial. Five studies have been done in Sweden. This overview, based on 282,777 women followed for 5-13 years in randomised trials in Malmö, Kopparberg, Ostergötland, Stockholm, and Gothenburg, reveals a 24% (95% confidence interval 13-34%) significant reduction of breast cancer mortality among those invited to mammography screening compared with those not invited. To avoid the potential risk of differential misclassification causes of death were assessed by an independent end-point committee after a blinded review of all fatal breast cancer cases. The mortality reduction was similar, irrespective of the end-point used for evaluation (\"breast cancer as underlying cause of death\" or \"breast cancer present at death\"). There was a consistent risk reduction associated with screening in all studies, although the point estimate of the relative risk for all ages varied non-significantly between 0.68 and 0.84. The cumulative breast cancer mortality by time since randomisation was estimated at 1.3 per 1000 within 6 years in the invited group compared with 1.6 in the control group. The corresponding figures after 9 years are 2.6 and 3.3 and after 12 years 3.9 and 5.1. The largest reduction of breast cancer mortality (29%) was observed among women aged 50-69 at randomisation. Among women 40-49 there was a non-significant 13% reduction. In this younger age group cumulative breast cancer mortality was similar in the invited and control group during the first 8 years of follow-up. After 8 years there was a difference in favour of the invited women. There was no evidence of any detrimental effect of screening in terms of breast cancer mortality in any age group. Among women aged 70-74 years screening seems to have had only a marginal impact.", "Noisy breathing at the end of life (noisy breathing (\"NB\") occurs in up to 90% of people. Interventions have not been systematically evaluated. There has been clinical observation coupled with a proposed mechanism of effect that supports a role for octreotide in management of NB. The aim of this phase II study was to assess ten completed participants for the feasibility of an adequately powered phase III study. This randomized, double-blind, crossover pilot trial recruited participants from an inpatient palliative unit. Participants while well and their proxies simultaneously provided written informed consent. If NB were encountered, people were randomized to 200 mcg octreotide or 400 mcg hyoscine hydrobromide subcutaneously. If subsequent treatment was needed, the other medication was administered. A five point categorical scale documented the nurses' assessment of secretions over six hours. Eighty participants were consented of whom 10 (3 females, 7 males; median age 79, all with advanced cancer) received medication, five in each arm. There was no difference in the median time to administration of the second medication (3 hours). Two participants in each arm had a 2 category reduction of intensity after the second medication. Although feasible to consent and study this population in a way that respects autonomy and dignity even in the terminal hours of life, this pilot study suggests reconsideration of the pharmacological interventions (choice of agents, dosing, timing of dosing and pharmacokinetic profiles), standardizing of non-pharmacological care; and ways to measure directly family distress before further randomized studies for this symptom.", "Interventions to increase physical activity among breast cancer survivors are needed to improve health and quality of life and possibly to reduce the risk of disease recurrence and early mortality. Therefore, we report the feasibility and preliminary outcomes of a pilot randomized trial designed to increase physical activity in sedentary breast cancer survivors receiving hormone therapy.\n Forty-one sedentary women on estrogen receptor modulators or aromatase inhibitors for stage I, II, or IIIA breast cancer were randomly assigned to receive a 12-wk multidisciplinary physical activity behavior change intervention or usual care.\n Recruitment was 34%, intervention adherence was 99%, and complete follow-up data were obtained on 93%. Most participants (93%) were white with mean age of 53 +/- 9 yr. Differences favoring the intervention group were noted for accelerometer physical activity counts (mean difference = 72,103; 95% confidence interval (CI) = 25,383-119,000; effect size (d) = 1.02; P = 0.004), aerobic fitness (mean difference = 2.9; 95% CI = -0.1 to 5.8; d = 0.64; P = 0.058), back/leg muscle strength (mean difference = 12.3; 95% CI = 0.4-15.9; d = 0.81; P = 0.017), waist-to-hip ratio (mean difference = -0.05; 95% CI = -0.01 to -0.08; d = -0.77; P = 0.018), and social well-being (mean difference = 2.0; 95% CI = 0.3-3.8; d = 0.76; P = 0.03). However, the intervention group also reported a greater increase in joint stiffness (mean difference = 1.1; 95% CI = 0.1-2.2; d = 0.70; P = 0.04).\n A behavior change intervention for breast cancer survivors based on the social cognitive theory is feasible and results in potentially meaningful improvements in physical activity and selected health outcomes. Confirmation in a larger study is warranted.", "Although researchers suggest treatments that provide patients with an active coping strategy may increase patients' sense of self-efficacy, previous studies have not measured patients' self-efficacy.\n Eighteen women receiving chemotherapy for breast cancer were randomized to efficacy-enhancing experimental (n = 10) and usual-care control (n = 8) groups. The experimental group received five interventions delivered monthly. Variables--quality of life, symptom distress, and self-care self-efficacy--were measured at baseline and at 4 and 8 months later.\n At 4 and 8 months the interaction effects for the Functional Assessment of Cancer Treatment-Breast, used to measure quality of life, ranged from small for functional concerns to large for social concerns. Interaction effects for symptom distress, measured by the Symptom Distress Scale, were large. Interaction effects for self-care self-efficacy ranged from small for Enjoying Life and Stress Reduction, medium for Stress Reduction, and large for Making Decisions.\n Interventions to promote self-efficacy may increase quality of life and decrease distress for women diagnosed with breast cancer.", "Among women who practice breast self-examination (BSE), breast cancers may be detected when they are at an earlier stage and are smaller than in women who do not practice BSE. However, the efficacy of breast self-examination for decreasing breast cancer mortality is unproven. This study was conducted to determine whether an intensive program of BSE instruction will reduce the number of women dying of breast cancer.\n From October 1989 through October 1991, 266,064 women associated with 519 factories in Shanghai were randomly assigned to a BSE instruction group (132,979 women) or a control group (133,085 women). Initial instruction in BSE was followed by reinforcement sessions 1 and 3 years later, by BSE practice under medical supervision at least every 6 months for 5 years, and by ongoing reminders to practice BSE monthly. The women were followed through December 2000 for mortality from breast cancer. Cumulative risk ratios of dying from breast cancer were estimated using Cox proportional hazards models. All statistical tests were two-sided.\n There were 135 (0.10%) breast cancer deaths in the instruction group and 131 (0.10%) in the control group. The cumulative breast cancer mortality rates through 10 to 11 years of follow-up were similar (cumulative risk ratio for women in the instruction group relative to that in the control group = 1.04, 95% confidence interval = 0.82 to 1.33; P =.72). However, more benign breast lesions were diagnosed in the instruction group than in the control group.\n Intensive instruction in BSE did not reduce mortality from breast cancer. Programs to encourage BSE in the absence of mammography would be unlikely to reduce mortality from breast cancer. Women who choose to practice BSE should be informed that its efficacy is unproven and that it may increase their chances of having a benign breast biopsy.", "To test the value of telephone-administered cognitive-behavioral therapy in a study of patients with breast cancer.\n Women were assigned randomly to a therapy group or an assessment-only control group.\n A tertiary cancer treatment center serving rural areas of North Dakota and Minnesota.\n Women were recruited within three to four months of stage I (n = 27) or stage II (n = 26) breast cancer diagnosis. Age ranged from 30-82 (mean = 51.5 years). Most participants (n = 35) underwent a modified radical mastectomy; 17 underwent a lumpectomy.\n Therapy involved 10 30-minute (or less) telephone sessions. Data that were collected from mailed questionnaires included psychological distress (Profile of Mood States), perceived stress, coping (Coping Response Indices-Revised), quality of life (Medical Outcome Scale), and satisfaction with therapy. Measures were completed at baseline and at 4- and 10-month follow-up intervals.\n Telephone therapy, stress, coping, and quality of life.\n With time, women in the therapy and control groups reported reduced stress and improved quality of life. However, significant reductions in some kinds of distress (anxiety, anger, depression, and confusion) were not observed. Most therapy participants liked the telephone treatment sessions but showed only modest improvement (less anxiety and confusion) compared with women in the control group.\n Most patients reported being comfortable with the telephone therapy and said that they felt better as a result of it. However, the outcome data showed that telephone therapy--as carried out in this study--produced only modest benefits. Researchers need to consider who is best for delivering such therapy.\n Providing telephone therapy to patients with breast cancer has potential benefits, and nurses may be the appropriate professionals to administer the therapy.", "To determine the effect of exercise on quality of life in (a) a randomized controlled trial of exercise among recently diagnosed breast cancer survivors undergoing adjuvant therapy and (b) a similar trial among post-treatment survivors.\n Fifty newly diagnosed breast cancer survivors were recruited through a hospital-based tumor registry and randomized to a 6-month, home-based exercise program (n=25) or a usual care group (n=25). In a separate trial, 75 post-treatment survivors were randomized to a 6-month, supervised exercise intervention (n=37) or to usual care (n=38). Participants in both studies completed measures of happiness, depressive symptoms, anxiety, stress, self-esteem, and quality of life at baseline and 6 months.\n Forty-five participants completed the trial for newly diagnosed survivors and 67 completed the trial for post-treatment survivors. Good adherence was observed in both studies. Baseline quality of life was similar for both studies on most measures. Exercise was not associated with quality of life benefits in the full sample of either study; however exercise was associated with improved social functioning among post-treatment survivors who reported low social functioning at baseline (p<0.05).\n Exercise did not affect quality of life in either recently diagnosed or post-treatment breast cancer survivors; however this may be due in part to relatively high baseline functioning among participants in both studies. Strategies for future research include limiting enrollment to survivors who report reduced quality of life on screening questionnaires and targeting survivor subgroups known to be at particular risk for quality of life impairment.\n (c) 2009 John Wiley & Sons, Ltd.", "The purpose of this randomized control trial was to verify the effectiveness of a brief group intervention that combines stress management psycho-education and physical activity (ie, independent variable) intervention in reducing fatigue and improving energy level, quality of life (mental and physical), fitness (VO 2submax), and emotional distress (ie, dependent variables) in breast cancer survivors. This study applied Lazarus and Folkman stress-coping theoretical framework, as well as Salmon's unifying theory of physical activity. Eighty-seven French-speaking women who had completed their treatments for nonmetastatic breast cancer at a university hospital in Quebec City, Canada, were randomly assigned to either the group intervention (experimental) or the usual-care (control) condition. Data were collected at baseline, postintervention, and at 3-month follow-up. The 4-week group intervention was cofacilitated by 2 nurses. Results showed that participants in the intervention group showed greater improvement in fatigue, energy level, and emotional distress at 3-month follow-up, and physical quality of life at postintervention, compared with the participants in the control group. These results suggest that a brief psycho-educational group intervention focusing on active coping strategies and physical activity is beneficial to cancer survivors after breast cancer treatments.", "The purpose of this randomized study was to investigate whether a nursing intervention using Orem's self-care theory as a framework would affect subjective distress, side effects and quality of life as perceived by breast cancer patients receiving curative radiation therapy. The intervention consisted of five 30-min sessions once a week during the treatment period and two follow-up sessions after completion of treatment. The experimental group consisted of 67 patients, as did the control group. Measurements were collected five times: at baseline before commencement of treatment, at weeks 3 and 5 (completion of treatment) and follow-up periods of 2 weeks and 3 months. No measurable effect of the nursing intervention was found for side effects or quality of life but nursing intervention proved to have a positive effect in minimizing stress reactions (p = < 0.05). It is suggested that a nursing intervention should be implemented for breast cancer patients receiving curative radiation therapy.", "To determine functional and psychological benefits of a 12 week supervised group exercise programme during treatment for early stage breast cancer, with six month follow-up.\n Pragmatic randomised controlled prospective open trial.\n Three National Health Service oncology clinics in Scotland and community exercise facilities.\n 203 women entered the study; 177 completed the six month follow-up.\n Supervised 12 week group exercise programme in addition to usual care, compared with usual care.\n Functional assessment of cancer therapy (FACT) questionnaire, Beck depression inventory, positive and negative affect scale, body mass index, seven day recall of physical activity, 12 minute walk test, and assessment of shoulder mobility.\n Mixed effects models with adjustment for baseline values, study site, treatment at baseline, and age gave intervention effect estimates (intervention minus control) at 12 weeks of 129 (95% confidence interval 83 to 176) for metres walked in 12 minutes, 182 (75 to 289) for minutes of moderate intensity activity reported in a week, 2.6 (1.6 to 3.7) for shoulder mobility, 2.5 (1.0 to 3.9) for breast cancer specific subscale of quality of life, and 4.0 (1.8 to 6.3) for positive mood. No significant effect was seen for general quality of life (FACT-G), which was the primary outcome. At the six month follow-up, most of these effects were maintained and an intervention effect for breast cancer specific quality of life emerged. No adverse effects were noted.\n Supervised group exercise provided functional and psychological benefit after a 12 week intervention and six months later. Clinicians should encourage activity for their patients. Policy makers should consider the inclusion of exercise opportunities in cancer rehabilitation services. Trial registration Current controlled trials ISRCTN12587864 [controlled-trials.com].", "To determine the feasibility and efficacy of a physical activity behavioural change intervention in managing cancer-related fatigue among gynaecological cancer survivors during and post anti-cancer treatments.\n A two arm, single blind, randomised controlled trial was conducted within the Northern Ireland regional Cancer Centre. Thirty three sedentary gynaecological cancer survivors (stage I-III; ≤3 years post diagnosis), experiencing cancer-related fatigue (mild-severe) took part. Participants were randomly assigned to a behavioural change, moderate intensity physical activity intervention (n=16) or a Contact Control group (n=17). The primary outcome was fatigue (Multidimensional Fatigue Symptom Inventory-Short Form and Functional Assessment in Chronic Illness Therapy-Fatigue subscale). Secondary outcomes included quality of life, physical functioning, positive and negative affect, depression, body composition, sleep dysfunction and self-reported physical activity. Feasibility was assessed based on the recruitment rate, programme and physical activity adherence and participants' programme evaluation, including optional focus groups (n=16).\n Twenty five percent of eligible women took part (33/134). Participants were 8.7 (SD=9.1) months post diagnosis, with a mean age of 53 (SD=10.3) years. The majority of the sample had a diagnosis of ovarian (n=12) or endometrial cancer (n=11). Significant differences favouring the intervention group were observed for fatigue at 12 weeks and 6 months follow-up (12 week: mean difference=-11.06; 95% confidence interval (CI)=-21.89 to -0.23; effect size (d)=0.13; p=0.046; 6 month: mean difference=-19.48; 95% CI=-19.67 to -19.15; effect size (d)=0.20; p=0.01). A mean of 10 calls (SD=1.2 calls) were delivered to the Physical Activity Group, and 10 (SD=1.6 calls) to the CC group. The intervention was positively perceived based on exit questionnaire and focus group findings.\n A physical activity behavioural change intervention for gynaecological cancer survivors is feasible in terms of participants' programme adherence and evaluation, and the intervention demonstrates improvements in fatigue. However, confirmation in the form of a larger fully powered RCT is warranted.\n Copyright © 2011 Elsevier Inc. All rights reserved.", "We have recently reported the psychological outcome of a group Cognitive Behaviour Therapy (CBT) intervention with patients who had metastatic breast cancer. The data of 92 patients who were retained at the first follow-up assessment revealed short-term improvements on measures of mood and self-esteem amongst therapy participants. These changes were not sustained at the 3- and 6-month follow-up assessments. This report describes a survival analysis of 121 patients who entered the study, at 5 years after its commencement. The analysis, based on the Cox Proportional Hazards Regression model, revealed no survival advantage associated with the intervention. Only medical prognostic factors such as Eastern Cooperative Oncology Group (ECOG) performance status, visceral metastases and chemotherapy treatment significantly predicted patients' survival time. The findings of this study are compared with those of two earlier studies which also examined the survival effects of a group psychological intervention with metastatic breast cancer patients.\n Copyright 1999 John Wiley & Sons, Ltd.", "The value of routine follow-up with frequent visits to a breast cancer specialist-both in terms of detection of recurrence and patient satisfaction-has been questioned. The aim of this study was to compare nurse-led follow-up on demand versus physician follow-up after breast cancer treatment with regards to patients' well-being, satisfaction, access to medical care and medical safety. Two hundred and sixty-four consecutively selected women with newly diagnosed breast cancer, classified as UICC stage I or stage II, were randomised to follow-up at two hospitals in Sweden, either by routine medical follow-up, the physician group (PG, n=131), or on demand by a specialist nurse, the nurse group (NG, n=133). Measures were done at baseline and twice a year over a period of 5 years by means of a questionnaire containing the Hospital Anxiety and Depression Scale (HAD), and the Satisfaction and Accessibility (SaaC) scale. Number of contacts with the health care services, number of diagnostic procedures, and time to recurrence or death were monitored. The ratings of HAD and SaaC did not show any statistically significant differences between the groups. The levels of anxiety and depression were generally low and levels of patient satisfaction high. There were no differences between the groups concerning time to recurrence or death. This study indicates that women with breast cancer in stages I to II can be followed up by a specialist nurse with high patient satisfaction and good medical safety.", "This paper reviews the survival outcome from the randomized Phase III trials in solid tumours published on behalf of, or in collaboration with, the Cancer Therapy Committee (CTC) of the British Medical Research Council over a 30-year period to 31 December 1995. We review briefly the innovations in statistical methodology that have occurred over the period. We also note the ways in which standards of reporting the trials have improved, with more recent publications including, for example, estimates of the size of effect and confidence intervals. In all, 32 trials, involving over 5000 deaths in more than 8000 patients, have been published. Tumour types have included bladder, bone, brain, cervix, colon and rectum, head and neck, kidney, lung, ovary, prostate and skin. This paper presents a bibliography of these trials and gives details of the treatment comparisons made, the numbers of patients randomized and included in the analysis for each treatment arm, the observed numbers of deaths, and an estimate of the hazard ratio with associated 95% confidence intervals. The bibliography also indicates the main endpoint of each trial, whether recurrence-free survival or survival, and whether the trial was aimed at finding a difference or showing equivalence. The MRC trials have made an impact on both clinical practice and research activities. For example, the lung cancer programme has helped to establish the role of chemotherapy in small cell lung cancer and has developed better palliative treatment for non-small cell lung cancer. Trials of the radiosensitizer misonidazole have demonstrated that it has no role in the treatment of a number of cancers, trials of hyperbaric oxygen have defined the biological activity of this approach, and the appropriate dose of radiotherapy in patients with brain tumours has been found. The individual trials recruited between 44 and 824 patients (median 213). A better measure of the information in a trial is the number of deaths reported, which varied from 28 to 661 (median 145). A large proportion of the comparisons (8/29 or 28%) anticipating a survival difference, demonstrated such a difference at the 5% level of significance. Despite this, it is concluded that some of the trials should have been larger. In such cases, hindsight suggests either that an overoptimistic view of the anticipated survival benefit was taken at the design stage, or, for equivalence trials, the planned confidence interval was too wide for definitive statements to be made. As a consequence, the current CTC profolio of ongoing randomized trials open to patient accrual at 1 January 1996 have a projected median size of 600 and range from 120 to 2000 patients.", "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.", "Studies have shown that a majority of women with a family history of breast cancer have exaggerated perceptions of their own risk of this disease and experience excessive anxiety. In response to the need to communicate more accurate risk information to these women, specialized programs for breast cancer risk counseling have been initiated in medical centers across the United States.\n Our purpose was 1) to evaluate the impact of a standardized protocol for individualized breast cancer risk counseling on comprehension of personal risk among first-degree relatives of index breast cancer patients and 2) to identify women most and least likely to benefit from such counseling.\n This study is a prospective randomized trial comparing individualized breast cancer risk counseling to general health counseling (control). We studied 200 women aged 35 years and older who had a family history of breast cancer in a first-degree relative. Women with a personal history of cancer were excluded. Risk comprehension was assessed as the concordance between perceived \"subjective\" lifetime breast cancer risk and estimated \"objective\" lifetime risk.\n The results of logistic regression analysis showed that women who received risk counseling were significantly more likely to improve their risk comprehension, compared with women in the control condition (odds ratio [OR] = 3.5; 95% confidence interval [CI] = 1.3-9.5; P = .01). However, in both groups, about two thirds of women continued to overestimate their lifetime risks substantially following counseling. Examination of subjects by treatment interaction effects indicated that risk counseling did not produce improved comprehension among the large proportion of women who had high levels of anxious preoccupation with breast cancer at base line (P = .02). In addition, white women were less likely to benefit than African-American women (OR = 0.34; 95% CI = 0.11-0.99; P = .05).\n Efforts to counsel women about their breast cancer risks are not likely to be effective unless their breast cancer anxieties are also addressed.\n Attention to the psychological aspects of breast cancer risk will be critical in the development of risk-counseling programs that incorporate testing for the recently cloned breast cancer susceptibility gene, BRCA1 (and BRCA2 when that gene has also been cloned).", "The randomized controlled trial (RCT) is the gold standard for establishing new therapies in clinical oncology. Here we document changes with time in design, sponsorship, and outcomes of oncology RCTs.\n Reports of RCTs evaluating systemic therapy for breast, colorectal (CRC), and non-small-cell lung cancer (NSCLC) published 1975 to 2004 in six major journals were reviewed. Two authors abstracted data regarding trial design, results, and conclusions. Conclusions of authors were graded using a 7-point Likert scale. For each study the effect size for the primary end point was converted to a summary measure.\n A total of 321 eligible RCTs were included (48% breast, 24% CRC, 28% NSCLC). Over time, the number and size of RCTs increased considerably. For-profit/mixed sponsorship increased substantially during the study period (4% to 57%; P < .001). There was increasing use of time-to-event measures (39% to 78%) and decreasing use of response rate (54% to 14%) as primary end point (P < .001). Effect size remained stable over the study period. Authors have become more likely to strongly endorse the experimental arm (P = .017). A significant P value for the primary end point and industry sponsorship were each independently associated with endorsement of the experimental agent (odds ratio [OR] = 19.6, 95% CI, 8.9 to 43.1, and OR = 3.5, 95% CI, 1.6 to 7.5, respectively).\n RCTs in oncology have become larger and are more likely to be sponsored by industry. Authors of modern RCTs are more likely to strongly endorse novel therapies. For-profit sponsorship and statistically significant results are independently associated with endorsement of the experimental arm.", "Much has been written about working with the dying. Few, if any, controlled studies have examined the application of principles set forth. The authors evaluate the effectiveness of working with dying cancer patients by assessing changes in quality of life, physical functioning, and survival. One-hundred twenty men with end-stage cancer were randomly assigned to experimental or control groups; the 62 experimental group patients were seen regularly by a counselor. Patients were assessed before random assignment and at one, three, six, nine, and 12 months on quality of live and functional status. Experimental group patients improved significantly more than the control group on quality of life within three months. Functional status and survival did not differ between groups. A subsample of lung cancer patients provided cross-validation of findings. Although survival was not expected to differ, it was predicted that functioning would be enhanced if quality of life improved. One interpretation is that little can be done to alter physical function and survival when intervention occurs late in the progression of a fatal disease. This in no way reduces the value of improving overall quality of life, since enhancing the quality of survival for end-stage cancer patients is a high priority medical goal.", "There has been much debate about the value of screening mammography. Here we update the overview of the Swedish randomised controlled trials on mammography screening up to and including 1996. The Kopparberg part of the Two-County trial was not available for the overview, but the continuation of the Malmö trial (MMST II) has been added. The article also contains basic data from the trials that have not been presented before. Methods The trials (n=247010, invited group 129750, control group 117260) have been followed up by record linkage to the Swedish Cancer and Cause of Death Registers. The relative risks (RR) for breast cancer death and mortality were calculated for the invited and the control groups. The trial-specific as well as the age-specific effects were analysed. RRs were calculated by the density method, with total person-time experience of the cohort by time interval of follow-up as a basis for estimating mortality rates. We calculated weighted RRs and 95% CI with the Mantel-Haenszel procedure.\n The median trial time-the time from randomisation until the first round was completed for the control group or if the control group was not invited, until end of follow-up-was 6.5 years (range 3.0-18.1). The median follow-up time, the time from randomisation, to the end of follow-up, was 15.8 years (5.8-20.2). There were 511 breast cancer deaths in 1864770 women-years in the invited groups and 584 breast cancer deaths in 1688440 women-years in the control groups, a significant 21% reduction in breast cancer mortality (RR=0.79, 95% CI 0.70-0.89). The reduction was greatest in the age group 60-69 years at entry (33%). Looking at 5-year age groups, there were statistically significant effects in the age groups 55-59, 60-64, and 65-69 years (RR=0.76, 0.68, and 0.69, respectively). There was a small effect in women 50-54 years at randomisation (RR=0.95). The benefit in terms of cumulative breast cancer mortality started to emerge at about 4 years after randomisation and continued to increase to about 10 years. Thereafter the benefit in absolute terms was maintained throughout the period of observation. The age-adjusted relative risk for the total mortality was 0.98 (0.96-1.00).\n The advantageous effect of breast screening on breast cancer mortality persists after long-term follow-up. The recent criticism against the Swedish randomised controlled trials is misleading and scientifically unfounded.", "The purpose of this pilot study was to examine the effects of a combined cardiorespiratory and resistance exercise training program of short duration on the cardiorespiratory fitness, strength endurance, task specific functional muscle capacity, body composition and quality of life (QOL) in women breast cancer survivors. Sixteen subjects were randomly assigned to either a training (n = 8; age: 50 +/- 5 yrs) or control non-exercising group (n = 8; age: 51 +/- 10 yrs). The training group followed an 8-week exercise program consisting of 3 weekly sessions of 90-min duration, supervised by an experienced investigator and divided into resistance exercises and aerobic training. Before and after the intervention period, all of the subjects performed a cardiorespiratory test to measure peak oxygen uptake (VO2peak), a dynamic strength endurance test (maximum number of repetitions for chest and leg press exercise at 30 - 35 % and 100 - 110 % of body mass, respectively) and a sit-stand test. Quality of life was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 (EORTC-C30) questionnaire. In response to training, QOL, VO2peak (mean 3.9 ml/kg/min; 95 % CI, 0.93, 6.90) performance in leg press (17.9 kg; 95 % CI, 12.8, 22.4) and sit-stand test (- 0.67 s; 95 % CI, - 0.52, - 1.2) improved (p < or = 0.05). We observed no significant changes in the control group. Combined cardiorespiratory and resistance training, even of very brief duration, improves the QOL and the overall physical fitness of women breast cancer survivors.", "It has been shown that nonpharmacologic interventions are effective management techniques for cancer-related fatigue (CRF) in cancer survivors. However, few studies have investigated their effectiveness in patients who are receiving chemotherapy. In this study, the authors tested the effectiveness of a brief behaviorally oriented intervention in reducing CRF and improving physical function and associated distress in individuals who were receiving chemotherapy.\n For this randomized controlled trial, 60 patients with cancer were recruited and received either usual care or the intervention. The intervention was delivered on an individual basis on 3 occasions over a period from 9 weeks to 12 weeks, and the objective of the intervention was to alter fatigue-related thoughts and behavior. Primary outcomes were assessed as follows: CRF using the Visual Analogue Scale-Global Fatigue; physical functioning using the European Organization for Research and Treatment of Cancer Quality-of-Life Core 30 Questionnaire, and CRF-associated distress using the Fatigue Outcome Measure. Assessments were made on 4 occasions: at baseline (T0), at the end of chemotherapy (T1), 1 month after chemotherapy (T2), and 9 months after recruitment (T3). Normally distributed data were analyzed using t tests and random-slope/random-intercept mixed models.\n The intervention demonstrated a trend toward improved CRF, although this effect was reduced once confounders had been controlled statistically. There was a significant improvement in physical functioning (coefficient, 10.0; 95% confidence interval, 2.5-17.5; P = .009), and this effect remained once the confounding effects of mood disturbance and comorbid disorders were controlled statistically. No decrease in fatigue-related distress was detected.\n The behaviorally oriented intervention brought about significant improvements in physical functioning, indicated a trend toward improved CRF, but detected no effect for fatigue-related distress.\n (c) 2007 American Cancer Society.", "Cancer survivors are at increased risk for cardiovascular disease, diabetes, osteoporosis, and second primary tumors. Healthful lifestyle practices may improve the health and well-being of survivors. The FRESH START trial tested the efficacy of sequentially tailored versus standardized mailed materials on improving cancer survivors' diet and exercise behaviors.\n Five hundred forty-three individuals with newly diagnosed locoregional breast or prostate cancer were recruited from 39 states and two provinces within North America. Participants were randomly assigned either to a 10-month program of tailored mailed print materials promoting fruit and vegetable (F&V) consumption, reducing total/saturated fat intake, and/or increasing exercise or to a 10-month program of nontailored mailed materials on diet and exercise available in the public domain. Telephone surveys conducted at baseline and 1 year assessed body mass index (BMI), dietary consumption, physical activity, and other psychosocial/behavioral indices. Clinical assessments were conducted on a 23% subsample; information was used to validate self-reports.\n Five hundred nineteen participants completed the 1-year follow-up (4.4% attrition; sample characteristics: 57 +/- 10.8 years old, 83% white, 56% female, 64% overweight/obese, and 0% underweight). Although both arms significantly improved their lifestyle behaviors (P < .05), significantly greater gains occurred in the FRESH START intervention versus the control arm (practice of two or more goal behaviors: +34% v +18%, P < .0001; exercise minutes per week: +59.3 v +39.2 minutes, P = .02; F&V per day: +1.1 v +0.6 servings, P = .01; total fat: -4.4% v -2.1%, P < .0001; saturated fat: -1.3% v -0.3%, P < .0001; and BMI: -0.3 v +0.1 kg/m2, respectively, P = .004).\n Mailed material interventions, especially those that are tailored, are effective in promoting healthful lifestyle changes among cancer survivors. Further study is needed to determine sustainability, cost to benefit, and generalizability to other cancer populations.", "This pilot study examined the efficacy of two home-based exercise programs on alleviating fatigue and improving functional capacity in breast cancer survivors. Participants were randomly assigned into one of three groups: aerobic exercise (AE), resistance exercise (RE), or usual care control (CON). After receiving individualized instruction and training, participants assigned to the AE and RE groups were asked to perform the prescribed exercise(s) 3 times per week for 12 weeks at home. Both groups were instructed to keep their perceived exercise intensity in the \"fairly light\" to \"somewhat hard\" range using the Borg Perceived Exertion Scale. All participants completed the revised Piper Fatigue Scale (PFS) and the 6-minute walk test (6MWT) at baseline and 12-week post-exercise program. Analysis of pre- and post-training data revealed a significant reduction in fatigue levels on the PFS among participants in the AE group (Z=2.521, one-tailed P=0.006), and a significant improvement in the distance of the 6MWT for the RE group (Z=2.366, one-tailed P=0.009) at the end of 12-week study period. No significant changes in fatigue or functional status were observed in the CON group. Findings provide preliminary support for RE as a viable strategy for improving functional capacity in breast cancer survivors, while AE may be more effective in attenuating cancer-related fatigue. Incorporating RE training for future research may help advance the growing body of knowledge in symptom management for breast cancer survivors.", "To examine the effects of a seated exercise program on fatigue and quality of life (QOL) in women with metastatic breast cancer.\n Randomized, controlled, longitudinal trial.\n Outpatient clinic of a comprehensive cancer center.\n Convenience sample of 38 women who were beginning outpatient chemotherapy.\n Subjects were randomized to a control or intervention group; the intervention was performance of a seated exercise program using home videotape three times per week for four cycles of chemotherapy. All subjects completed the Functional Assessment of Chronic Illness Therapy Fatigue Version IV (FACIT F) at baseline and at the time of the next three cycles. Subjects were asked to document the frequency, duration, and intensity of all exercise participation on monthly calendars.\n Exercise, fatigue, and QOL.\n 32 subjects, 16 per group, completed the study follow-up. With a mixed modeling approach, total FACIT F scores for the entire sample declined at a significant rate (p = 0.003) beginning with cycle 3 but at a slower rate for the experimental group (p = 0.02). Fatigue scores indicated less increase and physical well-being subscale scores showed less decline for the experimental group (p = 0.008 and p = 0.02, respectively).\n Women with advanced breast cancer randomized to the seated exercise intervention had a slower decline in total and physical well-being and less increase in fatigue scores starting with the third cycle of chemotherapy.\n Seated exercise may be a feasible exercise program for women with advanced cancer for controlling fatigue and improving physical well-being.", "The efficacy of energy conservation and activity management (ECAM) for fatigue reduction and maintenance of functional performance has never been evaluated in adults with cancer who are undergoing treatment.\n A randomized clinical trial compared an ECAM intervention with a control intervention focused on nutrition. Individuals initiating chemotherapy, radiotherapy, or concurrent therapy for cancer were randomized to receive either the semistructured ECAM intervention (n = 200) or the control intervention (n = 196). Participants in each group participated in 3 telephone sessions with an oncology nurse during the first 5 weeks of treatment. Data on fatigue and limitation of functioning were obtained before cancer treatment and at two follow-up points that coincided with times of high fatigue for each type of treatment. The outcomes of interest included perception of fatigue and functional performance.\n A repeated-measures analysis of covariance using the type of cancer treatment as a covariate revealed a significant study group-by-time interaction indicating that the ECAM group experienced a greater decrease in fatigue over time compared with the control group (F(2,544) = 4.5; P = 0.01). The intervention was not associated with changes in overall functional performance.\n Individuals who received the ECAM intervention derived a modest but significant benefit from it. To achieve a more robust clinical benefit from the intervention, it may be necessary to manage other key symptoms in addition to fatigue. Research is needed to examine symptom clusters or combinations associated with negative outcomes as well as combination strategies for symptom management.\n Copyright 2004 American Cancer Society.", "A pilot research study was conducted at 2 cancer centers in Connecticut to determine the effect of a dance and movement program on quality of life and shoulder function in breast cancer survivors treated within the prior 5 years. Thirty-five women completed the trial that included a 12-week intervention, using The Lebed Method, Focus on Healing Through Movement and Dance. The study design was a randomized control trial with a wait list control group crossover to active treatment in weeks 13 to 25, with the treatment group receiving the program in weeks 1 to 12, and no program in weeks 13 to 25. Outcome measures were the Breast Cancer Quality of Life (FACT-B), Shoulder range of motion (ROM), and Body Image Scale. FACT-B significantly improved in the intervention group at 13 weeks from 102.0 +/- 15.8 to 116.7 +/- 16.9, compared to the wait list group 108.1 +/- 16.4 to 107.1 +/- 21.3 (time x group effect, P = .008). During the crossover phase, the FACT-B score increased in the wait list group and was stable in the treatment group. The overall effect of the training at 26 weeks was significant (time effect, P = .03), and the order of training was also significant (P = .015). Shoulder ROM increased in both groups at 13 weeks--15 degrees and 8 degrees in the intervention and wait list groups (Time effect, P = .03; time x group, P = .58). Body Image improved similarly in both groups at 13 weeks (time effect, P = .001; time x group, P = .25), and at 26 weeks. There was no significant effect of the order of training for these outcome measures. A dance movement program that addressed the physical and emotional needs of women following treatment for breast cancer substantially improved a breast cancer-specific quality-of-life measure. Larger studies are justified to determine the acceptability of this therapy as part of the continuum of care for breast cancer survivors.", "To determine whether dual-chamber rate-adaptive Closed Loop Stimulation (CLS) could prevent recurrence of Vasovagal Syncope (VVS).\n During VVS, an increase in myocardial contractility associated with a reduction of ventricular filling produces an increase in baroreceptor afferent flow and a consequent decrease in the heart rate. The CLS algorithm is a form of rate-adaptive pacing, which responds to myocardial contraction dynamics, by measuring variations in right ventricular intracardiac impedance: during an incipient VVS it could increase paced heart rate and avoid bradycardia, arterial hypotension and syncope.\n Fifty patients (27 males, mean age 59+/-18 year) with severe and recurrent vasovagal syncope and positive Head Up Tilt Test (HUTT) with cardioinhibition, received a CLS pacemaker (INOS2, Biotronik GmbH Co., Germany). The primary end point was recurrence of two VVSs during a minimum of 1 year of follow-up. Randomization between DDD-CLS and DDI mode (40 bpm) pacing was performed only during the first stage of the study (first year): 9/26 randomized to DDI mode (control group) and 17/26 in DDD-CLS mode. All the 24 patients recruited in the second stage of the study (second year) were programmed in DDD-CLS mode.\n Of the nine patients randomized to the DDI mode, seven had recurrences of syncope during the first year. At the end of the first year the nine patients were reprogrammed to the CLS mode and no syncope occurred after reprogramming. The 41 patients programmed to CLS had a mean follow-up of 19+/-4 months: none reported VVS, only four (10%) reported occasional presyncope and their quality of life greatly improved. Positive HUTT at the end of the first year failed to predict the clinical response to CLS pacing.\n The study demonstrates the effectiveness of CLS pacing in preventing cardioinhibitory VVS. A possible placebo effect of pacemaker implantation occurred in 22% of patients.", "To demonstrate the efficacy of radiochemotherapy (RCT) as the first choice of treatment for advanced unresectable head-and-neck cancer. To prove an expected benefit of simultaneously given chemotherapy, a two-arm randomized study with hyperfractionated accelerated radiochemotherapy (HF-ACC-RCT) vs. hyperfractionated accelerated radiotherapy (HF-ACC-RT) was initiated. The primary endpoint was 1-year survival with local control (SLC).\n Patients with Stage III and IV (UICC) unresectable oro- and hypopharyngeal carcinomas were randomized for HF-ACC-RCT with 2 cycles of 5-FU (600 mg/m(2)/day)/carboplatinum (70 mg/m(2)) on days 1--5 and 29--33 (arm A) or HF-ACC-RT alone (arm B). In both arms, there was a second randomization for testing the effect of prophylactically given G-CSF (263 microg, days 15--19) on mucosal toxicity. Total RT dose in both arms was 69.9 Gy in 38 days, with a concomitant boost regimen (weeks 1--3: 1.8 Gy/day, weeks 4 and 5: b.i.d. RT with 1.8 Gy/1.5 Gy). Between July 1995 and May 1999, 263 patients were randomized (median age 56 years; 96% Stage IV tumors, 4% Stage III tumors).\n This analysis is based on 240 patients: 113 patients with RCT and 127 patients with RT, qualified for protocol and starting treatment. There were 178 oropharyngeal and 62 hypopharyngeal carcinomas. Treatment was tolerable in both arms, with a higher mucosal toxicity after RCT. Restaging showed comparable nonsignificant different CR + PR rates of 92.4% after RCT and 87.9% after RT (p = 0.29). After a median observed time of 22.3 months, l- and 2-year local-regional control (LRC) rates were 69% and 51% after RCT and 58% and 45% after RT (p = 0.14). There was a significantly better 1-year SLC after RCT (58%) compared with RT (44%, p = 0.05). Patients with oropharyngeal carcinomas showed significantly better SLC after RCT (60%) vs. RT (40%, p = 0.01); the smaller group of hypopharyngeal carcinomas had no statistical benefit of RCT (p = 0.84). For both tumor locations, prophylactically given G-CSF was a poor prognostic factor (Cox regression), and resulted in reduced LRC (log-rank test: +/- G-CSF, p = 0.0072).\n With accelerated radiotherapy, the efficiency of simultaneously given chemotherapy may be not as high as expected when compared to standard fractionated RT. Oropharyngeal carcinomas showed better LRC after HF-ACC-RCT vs. HF-ACC-RT; hypopharyngeal carcinomas did not. Prophylactic G-CSF resulted in an unexpected reduced local control and should be given in radiotherapy regimen only with strong hematologic indication.", "Physical activity provides a number of physical and psychological benefits to cancer survivors, including lessening the impact of detrimental cancer-related symptoms and treatment side-effects (e.g. fatigue, nausea), and improving overall well-being and quality of life. The purpose of the present pilot study was to examine the physical and psychological benefits afforded by a 7-week yoga program for cancer survivors.\n Eligible participants (per-screened with PAR-Q/PAR-MED-X) were randomly assigned to either the intervention (n=20) or control group (n=18). All participants completed pre- and post-testing assessments immediately before and after the yoga program, respectively.\n The yoga program participants (M age=51.18 (10.33); 92% female) included primarily breast cancer survivors, on average 55.95 (54.39) months post-diagnosis. Significant differences between the intervention and the control group at post-intervention were seen only in psychosocial (i.e. global quality of life, emotional function, and diarrhea) variables (all p's <0.05). There were also trends for group differences, in the hypothesized directions, for the psychosocial variables of emotional irritability, gastrointestinal symptoms, cognitive disorganization, mood disturbance, tension, depression, and confusion (all p's <0.10). Finally, there were also significant improvements in both the program participants and the controls from pre- to post-intervention on a number of physical fitness variables.\n These initial findings suggest that yoga has significant potential and should be further explored as a beneficial physical activity option for cancer survivors. Future research might attempt to include a broader range of participants (e.g. other types of cancer diagnoses, male subjects), a larger sample size, and a longer program duration in an RCT.", "To determine the effects of exercise training on cardiopulmonary function and quality of life (QOL) in postmenopausal breast cancer survivors who had completed surgery, radiotherapy, and/or chemotherapy with or without current hormone therapy use.\n Fifty-three postmenopausal breast cancer survivors were randomly assigned to an exercise (n = 25) or control (n = 28) group. The exercise group trained on cycle ergometers three times per week for 15 weeks at a power output that elicited the ventilatory equivalent for carbon dioxide. The control group did not train. The primary outcomes were changes in peak oxygen consumption and overall QOL from baseline to postintervention. Peak oxygen consumption was assessed by a graded exercise test using gas exchange analysis. Overall QOL was assessed by the Functional Assessment of Cancer Therapy-Breast scale.\n Fifty-two participants completed the trial. The exercise group completed 98.4% of the exercise sessions. Baseline values for peak oxygen consumption (P =.254) and overall QOL (P =.286) did not differ between groups. Peak oxygen consumption increased by 0.24 L/min in the exercise group, whereas it decreased by 0.05 L/min in the control group (mean difference, 0.29 L/min; 95% confidence interval [CI], 0.18 to 0.40; P <.001). Overall QOL increased by 9.1 points in the exercise group compared with 0.3 points in the control group (mean difference, 8.8 points; 95% CI, 3.6 to 14.0; P =.001). Pearson correlations indicated that change in peak oxygen consumption correlated with change in overall QOL (r = 0.45; P <.01).\n Exercise training had beneficial effects on cardiopulmonary function and QOL in postmenopausal breast cancer survivors.", "One-hundred and twenty-four patients with metastatic breast cancer were randomised to either a group Cognitive Behaviour Therapy (CBT) intervention, or to a no-therapy control group condition. Both groups received standard oncological care; however, therapy recipients also attended eight weekly sessions of group CBT, followed by a family night, and three further monthly sessions. Patients completed the 'Profile of Mood States' (POMS) and the Coopersmith Self-esteem Inventory (CSI) before and after therapy, and at 3 and 6 month follow-up periods. Outcome data in the period following therapy showed reduced depression and total mood disturbance, as well as improved self-esteem amongst therapy participants, relative to a no-therapy control group. These improvements were no longer evident at the 3 or 6 month follow-up assessments. We also report on the difficulties associated with conducting a group intervention with this patient cohort." ]	Sixteen studies have been published since the last version of the review, without altering our conclusions. While published observational studies demonstrated that BPM was effective in reducing both the incidence of, and death from, breast cancer, more rigorous prospective studies (ideally randomized trials) are needed. BPM should be considered only among those at very high risk of disease. There is insufficient evidence that CPM improves survival and studies that control for multiple confounding variables are needed.
CD000253	[ "22009916", "8825017", "17268417" ]	[ "Carotenoids in Age-related Maculopathy Italian Study (CARMIS): two-year results of a randomized study.", "Multicenter ophthalmic and nutritional age-related macular degeneration study--part 2: antioxidant intervention and conclusions.", "Effect of lutein and antioxidant dietary supplementation on contrast sensitivity in age-related macular disease: a randomized controlled trial." ]	[ "The high concentration of carotenoids in the macula, plus evidence linking oxidative stress to age-related macular degeneration (AMD) and carotenoids to antioxidation, generated the hypothesis that higher antioxidant intakes can prevent AMD. The aim of this study was to determine whether nutritional supplementation with a targeted nutritional supplement improves visual acuity and visual function in AMD.\n In this multicenter, prospective open-label randomized study, 145 patients were randomly assigned to 2 different treatment groups. Interventions were lutein (10 mg), zeaxanthin (1 mg), astaxanthin (4 mg; AZYR SIFI, Catania, Italy), and antioxidants/vitamins supplementation formula or no dietary supplementation for 2 years. Primary outcome was mean changes in visual acuity (VA) at 12 and 24 months. Other measures included contrast sensitivity (CS) and National Eye Institute visual function questionnaire (NEI VFQ-25) scores at 12 and 24 months.\n Patients in the treated group showed stabilization of VA with significantly (p=0.003) better VA scores (81.4 ± 7.2) compared to the nontreated group (76.8 ± 8.9) at 24-month follow-up. An improvement in CS (p=0.001) and final mean NEI VFQ-25 composite scores at 12 and 24 months higher in treated group compared to nontreated group were also shown (p<0.001).\n Patients treated with lutein/zeaxanthin and astaxanthin together with other nutrients were more likely to report clinically meaningful stabilization/improvements in VA, CS, and visual function through 24 months compared with nontreated subjects. Further studies are needed with more patients and for longer periods of time.", "The experimental design, subjects, procedures and baseline data for the prospective double blind dry ARMD-antioxidant intervention study have been described in Part 1.\n At eight DVA medical centers, 32 patients (group one) were assigned a placebo and 39 patients (group two) a \"broad spectrum\" antioxidant capsule. Data was collected in five areas: demographic; ophthalmic; dietary analysis of daily food intake; serum analysis; and adverse gastrointestinal symptoms. Data was serially acquired at baseline, 6 months, 12 months and 18 months, and was analyzed by univariate repeated factors ANOVA, p = 0.05.\n Group two (antioxidant po BID) maintained their distance LogMAR visual acuity (p = 0.03), while there was a trend toward both stabilized near M print (p = 0.07) and 6 cycle/degree contrast sensitivity (p approximately 0.10), in left eyes. However, group two (antioxidant) also had increased cortical opacification of the right lens (p = 0.04), compared to group one (placebo). Self perceived stabilization of vision was reported by subjects in group two and supported the objective data (Pearson chi square; p = 0.05).\n A specific 14 component antioxidant capsule taken twice daily stabilized but did not improve dry ARMD over the study period of 1.5 years. The ARMD stabilized eyes had less advanced disease functionally but not by fundus appearance. Decreased intake of cardioprotective nutrients (vitamin E, zinc, magnesium, B6 and folate) in ARMD patients remained constant over the course of the trial.", "The aim of the study is to determine the effect of lutein combined with vitamin and mineral supplementation on contrast sensitivity in people with age-related macular disease (ARMD).\n A prospective, 9-month, double-masked randomized controlled trial.\n Aston University, Birmingham, UK and a UK optometric clinical practice.\n Age-related maculopathy (ARM) and atrophic age-related macular degeneration (AMD) participants were randomized (using a random number generator) to either placebo (n=10) or active (n=15) groups. Three of the placebo group and two of the active group dropped out.\n The active group supplemented daily with 6 mg lutein combined with vitamins and minerals. The outcome measure was contrast sensitivity (CS) measured using the Pelli-Robson chart, for which the study had 80% power at the 5% significance level to detect a change of 0.3 log units.\n The CS score increased by 0.07+/-0.07 and decreased by 0.02+/-0.18 log units for the placebo and active groups, respectively. The difference between these values is not statistically significant (z=-0.903, P=0.376).\n The results suggest that 6 mg of lutein supplementation in combination with other antioxidants is not beneficial for this group. Further work is required to establish optimum dosage levels." ]	There is accumulating evidence that taking vitamin E or beta-carotene supplements will not prevent or delay the onset of AMD. There is no evidence with respect to other antioxidant supplements, such as vitamin C, lutein and zeaxanthin, or any of the commonly marketed multivitamin combinations. Although generally regarded as safe, vitamin supplements may have harmful effects and clear evidence of benefit is needed before they can be recommended. People with AMD should see the related Cochrane review 'Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration' written by the same review team.
CD007113	[ "8179545" ]	[ "A randomized controlled trial in a hospital population of ultrasound measurement screening for the small for dates baby." ]	[ "Poor fetal growth is an important cause of perinatal mortality and morbidity. Based on the hypothesis that early diagnosis of fetal growth problems leads to more appropriate management and therefore, improved outcome, a randomized controlled trial of ultrasound measurement was performed on 1,528 women booked through a hospital antenatal clinic. This compared a number of perinatal outcomes between the group who had a routine 2-stage examination (early dating and 34-week scan) and a group who had only a dating scan and then additional scans as generated by their clinical situations. No significant differences could be found between the groups when these perinatal outcomes were considered. These results mirror previously published randomized controlled trials. Selection of women for third trimester ultrasound examination for suspected fetal growth problems should be based on careful clinical assessment and should not be routine." ]	There is limited evidence from randomised controlled trials to inform best practice for fetal surveillance regimens when caring for women with pregnancies affected by impaired fetal growth. More studies are needed to evaluate the effects of currently used fetal surveillance regimens in impaired fetal growth.
CD005189	[ "11786454", "1391559", "19572992", "10464834" ]	[ "Reducing antibiotic use for acute bronchitis in primary care: blinded, randomised controlled trial of patient information leaflet.", "[Antibiotic treatment for acute episodes of chronic obstructive pulmonary disease].", "Management of bronchiolitis without antibiotics: a multicentre randomized control trial in Bangladesh.", "Inhaled antibiotic therapy in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa." ]	[ "To assess whether sharing the uncertainty of the value of antibiotics for acute bronchitis in the form of written and verbal advice affects the likelihood of patients taking antibiotics.\n Nested, single blind, randomised controlled trial.\n Three suburban general practices in Nottingham Participants: 259 previously well adults presenting with acute bronchitis.\n In group A, 212 patients were judged by their general practitioner not to need antibiotics that day but were given a prescription to use if they got worse and standard verbal reassurance. Half of them (106) were also given an information leaflet. All patients in group B (47) were judged to need antibiotics and were given a prescription and encouraged to use it.\n Antibiotic use in the next two weeks. Reconsultation for the same symptoms in the next month.\n In group A fewer patients who received the information leaflet took antibiotics compared with those who did not receive the leaflet (49 v 63, risk ratio 0.76, 95% confidence interval 0.59 to 0.97, P=0.04). Numbers reconsulting were similar (11 v 14). In group B, 44 patients took the antibiotics.\n Most previously well adults with acute bronchitis were judged not to need antibiotics. Reassuring these patients and sharing the uncertainty about prescribing in a information leaflet supported by verbal advice is a safe strategy and reduces antibiotic use.", "Antibiotic therapy for acute episodes of chronic obstructive pulmonary disease (COPD) is a controversial issue still not clarified. In order to evaluate the effectivity of the antibiotic therapy, we designed a double-blind controlled and randomized clinical trial, in which 90 patients hospitalized due to an acute episode of COPD were divided into three groups: group I, cotrimoxazole (29 patients); group II, amoxicillin-clavulanic acid (32 patients) and group III, placebo (29 patients). Gasometric and spirometric measures were taken in addition to clinical evaluation at hospital admission and discharge using a numerical valoration system. All patients were treated with common bronchodilators. The three groups were homogeneous at their admission and there were no statistical differences at their discharge. We conclude that antibiotics do not play a relevant role in the improvement of acute episodes of COPD.", "To ascertain that antibiotics have no role in the management of bronchiolitis.\n Multicentre randomized control trial (RCT).\n Five purposively selected teaching hospitals in Bangladesh.\n Children under 24 months old with bronchiolitis.\n Children were randomized into three groups of therapeutic interventions: parenteral ampicillin (P-Ab), oral erythromycin (O-Ab) and no antibiotic (N-Ab) in adjunct to supportive measures.\n Clinical improvement was assessed using 18 symptoms/signs which were graded on a two-point recovery scale of 'rapid' and 'gradual', indicating improvement within 'four days' and 'beyond four days', respectively.\n Each intervention group consisted of 98 +/- 1 children having comparable clinico-epidemiological characteristics at the baseline. The trial revealed that most chesty features (features appearing to arise from chest, i.e. cough, breathing difficulty, wheeze, chest indrawing, tachypnoea, tachycardia, rhonchi and crepitation) demonstrated a gradual recovery, beyond 4th admission day and, not differing among the three intervention groups (p > 0.23, p < 0.62, p = 0.54, p < 0.27, p = 0.75, p = 0.76, p = 0.81, p > 0.98, respectively). Most non-chesty features (features appearing to arise away from chest, i.e. feeding/sleeping difficulties, social smile, restlessness, inconsolable crying, nasal flaring, fever and hypoxaemia) demonstrated a rapid recovery, within 4 days, remaining comparable among the three intervention groups (p < 0.07, p = 0.65, p = 0.24, p < 0.61, p = 0.22, p = 0.84, p = 0.29 and p = 0.96, respectively). However, nasal symptoms (runny nose and nasal blockage) also showed no difference among groups (p = 0.36 and p = 0.66, respectively). Thus, the dynamics of clinical outcome obviates that children not receiving antibiotics had similar clinical outcome than those who did.\n In hospital settings, managing bronchiolitis with only supportive measures but without antibiotics remains preferable.", "The aim of this study was to investigate the long-term effectiveness and safety of inhaled antibiotic treatment in non-cystic fibrosis patients with bronchiectasis and chronic infection by Pseudomonas aeruginosa, after standard endovenous and oral therapy for long-term control of the infection had failed. After completing a 2-week endovenous antibiotic treatment to stabilize respiratory status, 17 patients were randomly allocated to a 12-month treatment either with inhaled ceftazidime and tobramycin (group A) or a symptomatic treatment (group B). One patient from group A abandoned inhaled treatment because of bronchospasm and another from group B died before the end of the study. The remaining 15 patients, seven from group A and eight from group B, completed the study. Both groups had similar previous characteristics. The number of admissions and days of admission (mean +/- SEM) of group A [0.6 (1.5) and 13.1 (34.8)] were lower than those of group B [2.5 (2.1) and 57.9 (41.8)] (P < 0.05). Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), PAO2 and PACO2 were similar in the two groups at the end of follow-up, showing a comparable decline in these parameters. There were no significant differences either in the use of oral antibiotics or in the frequency of emergence of antibiotic-resistant bacteria between groups. Microbiological studies suggested that several patients had different Pseudomonas aeruginosa strains. None of the patients presented impaired renal or auditory function at the end of the study. This study suggests that long-term inhaled antibiotic therapy may be safe and lessen disease severity in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa which do not respond satisfactorily to antibiotics administered via other routes." ]	This review found minimal evidence to support the use of antibiotics for bronchiolitis. Research to identify a possible small subgroup of patients who have complications from bronchiolitis such as respiratory failure and who may benefit from antibiotics is justified.
CD002102	[ "15197202", "10735495", "12847369", "15339325", "3191758", "7995187", "23839620", "7813338", "8692511", "11600473", "18085337", "15622577", "8765249", "15812583", "20091310", "12679946", "14738324", "20127342", "9864116", "15467559" ]	[ "Improved sphincter preservation in low rectal cancer with high-dose preoperative radiotherapy: the lyon R96-02 randomized trial.", "Sphincter-sparing surgery after preoperative radiotherapy for low rectal cancers: feasibility, oncologic results and quality of life outcomes.", "Direct repair vs. overlapping sphincter repair: a randomized, controlled trial.", "Adjuvant biofeedback following anal sphincter repair: a randomized study.", "Prospective trial of supranormal values of survivors as therapeutic goals in high-risk surgical patients.", "Loperamide improves anal sphincter function and continence after restorative proctocolectomy.", "Hypertonic saline for intraoperative fluid therapy in transurethral resection of the prostate.", "Randomized trial of internal anal sphincter plication with pelvic floor repair for neuropathic fecal incontinence.", "Comparison of Burch and lyodura sling procedures for repair of unsuccessful incontinence surgery.", "Can endoscopic papillary balloon dilation really preserve sphincter of Oddi function?", "Fine-tuning of the extent of lateral internal sphincterotomy: spasm-controlled vs. up to the fissure apex.", "A prospective, randomized, controlled clinical trial of placement of the artificial bowel sphincter (Acticon Neosphincter) for the control of fecal incontinence.", "Randomized prospective comparison of needle colposuspension versus endopelvic fascia plication for potential stress incontinence prophylaxis in women undergoing vaginal reconstruction for stage III or IV pelvic organ prolapse. The Continence Program for Women Research Group.", "Relationship between surgeon caseload and sphincter preservation in patients with rectal cancer.", "Randomized controlled trial between perineal and anal repairs of rectocele in obstructed defecation.", "Operative stress response and energy metabolism after laparoscopic cholecystectomy compared to open surgery.", "Effects of open vs. laparoscopic cholecystectomy on oxidative stress.", "Is sphincter preservation reasonable in all patients with rectal cancer?", "Comparison of laparoscopic rectopexy with open technique in the treatment of complete rectal prolapse: clinical and functional results.", "Randomized clinical trial of intra-anal electromyographic biofeedback physiotherapy with intra-anal electromyographic biofeedback augmented with electrical stimulation of the anal sphincter in the early treatment of postpartum fecal incontinence." ]	[ "The potential advantage of high-dose preoperative radiotherapy to increase tumor response and improve the chance of sphincter preservation for low rectal cancer remains controversial. The aim of this trial was to evaluate the role of escalating the dose of preoperative radiation to increase sphincter-saving procedures.\n Patients with rectal carcinoma located in the lower rectum, staged T2 or T3, Nx, or M0 with endorectal sonography, and not involving more than two-thirds circumference, were randomly assigned to one of two groups: preoperative external-beam radiotherapy (EBRT; 39 Gy in 13 fractions over 17 days) versus the same EBRT with boost (85 Gy in three fractions) using endocavitary contact x-ray.\n Between 1996 and 2001, 88 patients were enrolled onto the study. A significant improvement was seen in favor of the contact x-ray boost for complete clinical response (24% v 2%) and for a complete or near-complete sterilization of the operative specimen (57% v 34%). A significant increase in sphincter preservation was observed in the boost group (76% v 44%; P =.004). At a median follow-up of 35 months, there was no difference in morbidity, local relapse, and 2-year overall survival.\n A dose escalation with endocavitary irradiation provides increased tumor response and sphincter preservation with no detrimental effect on treatment toxicity and early clinical outcome.", "The present study assesses the choice of surgical procedure, oncologic results and quality of life (QOL) outcomes in a retrospective cohort of 53 patients with low-lying rectal cancers (within 6 cm of the anal verge) treated surgically following preoperative radiotherapy (RT, median dose 45Gy) with or without concomitant 5-fluorouracil. QOL was assessed in 23 patients by using two questionnaires developed by the QOL Study Group of the European Organization for Research and Treatment of Cancer: EORTC QLQ-C30 and EORTC QLQ-CR38. After a median interval of 29 days from completion of RT, abdominoperineal resection (APR) was performed in 29 patients (55%), low anterior resection in 23 patients (20 with coloanal anastomosis) and transrectal excision in one patient. The 3-year actuarial overall survival and locoregional control rates were 71.4% and 77.5% respectively, with no differences observed between patients operated by APR or restorative procedures. For all scales of EORTC QLQ-C30 and EORTC QLQ-CR38, no significant differences in median scores were observed between the two surgical groups. Although patients having had APR tended to report a lower body image score (P = 0.12) and more sexual dysfunction in male patients, all APR patients tended to report better physical function, future perspective and global QOL. In conclusion, sphincter-sparing surgery after preoperative RT seems to be feasible, in routine practice, in a significant proportion of low rectal cancers without compromising the oncologic results. However, prospective studies are mandatory to confirm this finding and to clarify the putative QOL advantages of sphincter-conserving approaches.", "The aim of this study was to compare the results of two surgical techniques (direct end-to-end vs. overlapping) of delayed repair of a localized anterior defect of external anal sphincter after an obstetric trauma.\n During a five-year period, 23 patients were randomly assigned to direct end-to-end repair (n = 12) or overlapping sphincter repair (n = 11), using 2-0 PDS sutures. Two patients from each group had an internal anal sphincter defect that also was repaired. All patients had a normal pudendal nerve terminal motor latency preoperatively. Evaluations included endoanal ultrasound, anorectal manometry, and neurophysiologic evaluation. Continence was assessed by the Cleveland Clinic Continence Score (0-20; 0, perfect continence; 20, complete incontinence).\n The two groups were comparable with regard to age (median, 45 years), past history of sphincter repair (n = 2), and posterior vaginal repair. There was no major morbidity. The wound-healing rate was identical between the two groups. However, of the patients undergoing overlapping repair, two had fecal impaction, and one had a urinary retention. Median preoperative continence score was 17 in both the direct-repair group (score, 8-20) and the overlap group (score, 7-20). At a median follow-up of 18 months, the improvement in continence was similar between the two surgical groups, with a median continence score of 3, respectively. In both surgical groups there was a significant and similar improvement in maximum squeeze pressure and in the functional anal canal length postoperatively (P < 0.05), but the mean resting pressure was relatively unchanged. In the overlap group, one patient developed a unilaterally prolonged pudendal nerve terminal motor latency that was persistent 22 months after surgery, and two patients had impaired fecal evacuation postoperatively.\n This randomized, controlled study suggests that the outcome is similar whether direct end-to-end or overlapping repair of a sphincter defect is performed. Overlapping repair might be associated with more difficulties with fecal evacuation and a prolonged pudendal nerve terminal motor latency postoperatively.", "To evaluate the impact of adjuvant biofeedback following sphincter surgery.\n Thirty-eight patients were randomized into sphincter repair or sphincter repair plus biofeedback groups. Outcome measures included a symptom questionnaire, patient's rating of satisfaction with continence function and improvement, change in continence score, quality of life and anorectal physiology. Endoanal ultrasonography was also performed pre- and post-operatively.\n Immediately following surgery, there was no statistically significant difference in any of the functional or physiological variables between the groups. Continence and patient satisfaction scores improved with a mean difference of -0.48 (95% CI: -3.30-2.33, P = 0.73) and 1.03 (95% CI: -1.40-3.46, P = 0.39), respectively. Only the difference in embarrassment scores reached statistical significance (mean) 0.56 (95% CI: 0.12-0.99, P = 0.014). Resting and squeeze pressures also improved. Thirteen of 14 in the biofeedback and 11 of 17 (control) reported symptomatic improvement. In the biofeedback group, although not statistically significant continence and satisfaction scores improved and were sustained over time. In the control group, continence and satisfaction scores changed little between 3 and 12 months (P = NS). Quality of life measures improved within the biofeedback group but there was no statistical difference between the groups.\n Following surgery continence function improves in all patients but adjuvant biofeedback therapy improves quality of life and maintains symptomatic improvement over time.\n Copyright 2004 Blackwell Publishing Ltd", "Survivors of high-risk surgical operations were previously observed to have significantly higher mean CI, DO2, and VO2 than nonsurvivors. The hypothesis was proposed that increased CI and DO2 are circulatory compensations for increased postoperative metabolism. We tested this hypothesis in two series. In series 1, prospectively allocated by services, mortality and morbidity of the control group were significantly greater than those of the protocol group. In series 2, patients who fulfilled previously defined high-risk criteria were preoperatively randomized to one of three monitoring/treatment groups: CVP-control group, PA-control group and PA-protocol group. Postoperative mortalities in the CVP-control and PA-control groups were not statistically significantly different, but PA-protocol group mortality was significantly reduced compared with its control group. The PA-protocol group had reduced complications, duration of hospitalization, duration in ICU, and mechanical ventilation, and reduced costs when the PA catheter was placed preoperatively and used to augment circulatory responses.", "The physiological and clinical effects of loperamide treatment versus placebo were investigated in a randomized, double-blind, crossover study in patients operated with restorative proctocolectomy. Sixteen patients operated with endoanal mucosectomy and a handsewn ileal pouch-anal anastomosis and 14 patients operated with abdominal proctocolectomy and stapling of the pouch to the top of the anal canal were studied. While loperamide treatment increased resting anal pressure in both groups of patients by approximately 20% (P < 0.05), squeeze pressure was not affected. Loperamide did not affect pouch volume or contractility. Sensory thresholds and the recto/pouch-anal inhibitory reflex were not influenced by loperamide treatment. Clinical function was improved, with a reduced bowel frequency and an improved nighttime continence, with less soiling (P < 0.05) as well as need to wear a protective pad.", "We tested hypertonic saline solution (HS) to determine its effectiveness in surgical procedures for prostatic hypertrophy. We randomly selected 40 patients undergoing elective transurethral resection of the prostate for either infusion of HS (3% NaCl) at 4ml·kg(-1)·min(-1) (HS group) or lactated Ringer's solution (LR) at 8 ml·kg(-1)·min(-1) (LR group). Anesthesiologists regulated the intraoperative infusion rate as needed to maintain blood pressure. There were no differences in systolic blood pressure, heart rate, central venous pressure, or arterial blood oxygenation between the two groups. In the HS group, plasma sodium, chloride, and osmolality, measured in the recovery room, were significantly increased; however, they returned to preanesthetic levels the day after surgery. In the LR group, in contrast, plasma sodium decreased significantly and this lower value persisted for 1 day. An osmolar gap exceeding 10mOsm·kg(-1) was observed in 2 patients in the HS group, but plasma sodium remained at normal values. However, in the 1 patient in the LR group whose osmolar gap exceeded 10mOsm·kg(-1), plasma sodium was 115 mEq·I(-1). HS, at a low dose, is useful in the intraoperative management of transurethral resection of the prostate.", "This study was designed to examine the role of adjuvant internal anal sphincter plication in women with neuropathic fecal incontinence undergoing pelvic floor repair.\n We completed a randomized trial with symptomatic and physiologic assessment before and after surgery.\n There was no symptomatic advantage of adding internal sphincter plication; the mean improvement of functional score was 3.61 +/- 1.82 (standard deviation; P < 0.01) following pelvic floor repair alone compared with 2.80 +/- 1.66 (standard deviation; P < 0.01) when adjuvant internal and sphincter plication was added. The addition of internal sphincter plication was associated with a significant fall in maximum anal resting and squeezing pressures (P < 0.01).\n Addition of internal sphincter plication is not advised in women with neuropathic fecal incontinence treated by pelvic floor repair.", "To assess the effectiveness and late postoperative morbidity of the Burch procedure and the sling procedure for the treatment of recurrent urinary stress incontinence after vaginal hysterectomy and anterior repair.\n Clinical, urodynamic, and sonographic examinations were done on 77 women suffering with recurrent urinary stress incontinence. The women were randomized to two groups, modified Burch colposuspension and lyophilized dura mater sling surgery; 72 women were reexamined 32-48 months after these procedures.\n The cure rate at 32-48 months' follow-up was 86% for the Burch procedure and 92% for the sling. Women who had had the sling procedure demonstrated a clear decrease in maximal bladder capacity, from 330 to 240 mL (P < .05). In both groups, stress profiles demonstrated a shift of maximal pressure point toward the proximal urethra and a significant improvement in pressure transmission (P < .05). The post-operative patients who had persistent incontinence were found to have insufficient elevation of the bladder neck (less than 10 mm). The uroflow examination showed an increase of urination time in both groups. The incidence of bladder problems was 10% with the Burch procedure and 29% with the sling procedure; however, 13% of the Burch group developed rectoceles.\n Both procedures offer a high rate of success. We believe that the sling surgery should be used only in certain special cases because of its higher rate of complications, but that posterior vaginal repair should be considered after modified Burch colposuspension because of the possibility of rectocele and enterocele.", "Endoscopic papillary balloon dilation (EPBD) is assumed to preserve sphincter of Oddi function because it causes little trauma to the papilla. However, few studies have addressed this issue specifically. In this study, we investigated whether EPBD can preserve sphincter function, and evaluated whether or not such preservation has clinical significance.\n Seventy patients with common bile duct (CBD) stones were randomly assigned to EPBD or endoscopic sphincterotomy (EST). Sphincter of Oddi (SO) function was measured by endoscopic manometry before, one week after, and one year after treatment. Incidence of pneumobilia and later complications were compared between the two groups at one year. Series manometric data were compared within each group and between the two groups. For a more detailed analysis of the cumulative incidence of later complications, retrospective cohorts were added to the study groups, giving a total number of 235 patients in the EPBD group and 126 in the EST group.\n Baseline characteristics did not differ significantly between the 35 EPBD and 35 EST patients. CBD stones were discharged successfully in all cases. CBD pressure, SO basal and peak pressures, and contraction frequency decreased significantly at one week in both groups. The damage was more severe in the EST group, and SO contraction completely disappeared in 23 patients in this group. The incidence of pneumobilia was significantly lower in the EPBD group than in the EST group (p<0.01) whereas CBD stones recurred and cholecystitis appeared at a similar rate in both groups at one year. A complete series of manometric data up to one year was obtained in 55 patients; 28 in the post-EPBD and 27 in post-EST groups. In the post-EPBD group, SO basal and peak pressures significantly recovered at one year compared with data at one week but these measures still remained significantly lower than those before EPBD (p< 0.01). In the post-EST group, SO contraction did not recover even after one year. A Kaplan-Meier analysis of 235 EPBD and 126 EST patients for a median follow up of 37 months revealed significantly lower incidences of biliary complications such as recurrent CBD stones and cholangitis, and cholecystitis in the EPBD group than in the EST group (p<0.05). The risk of pneumobilia was also significantly lower in the EPBD group (p<0.01).\n Preservation of papillary function after EPBD was not complete but remained somewhat reduced. However, preservation was more successful with EPBD than with EST. Such preservation may be clinically beneficial for the prevention of later complications.", "This study was designed to compare the results of controlled lateral internal sphincterotomy by using anal calibrators with those of sphincterotomy up to the fissure apex in a randomized, prospective fashion.\n In the fissure apex group, sphincterotomy was extended to the level of the fissure apex, and in the spasm-controlled group, serial small sphincterotomies and anal caliber measurements followed until an anal caliber of 30 mm was obtained.\n The preoperative anal caliber was 24 +/- 1.9 (range, 20-28) mm and 24.9 +/- 2.44 (range, 19-28) mm in the spasm-controlled and fissure apex groups, respectively (P = 0.127). Postoperatively, the spasm-controlled group had a mean anal caliber of 31.5 +/- 1.28 (range, 30-32) mm, and the fissure apex group had 32.5 +/- 2.33 (range, 25-37) mm (P = 0.035). In the fissure apex group, a significant negative correlation was determined between the postoperative anal caliber and time of relief of pain (r = -0.568, P = 0.001). The early (7 and 28 days) postoperative anal incontinence scores were significantly higher in the fissure apex group (P = 0.002, P < 0.0001, respectively). A significant positive correlation between the anal caliber measurements and anal incontinence scores at 28 days and 2 months also was noted in the fissure apex group (r = 0.406, P = 0.023; and r = 0.364, P = 0.044).\n Controlled sphincterotomy provided a faster relief of pain, and it was associated with a lower rate of early postoperative disturbance of continence and an insignificantly lower rate of treatment failure compared with sphincterotomy up to the fissure apex.", "Severe fecal incontinence remains a disabling condition for the patient and a major therapeutic challenge for the physician. A series of observational studies have indicated that placement of an artificial bowel sphincter is associated with marked improvement of continence and quality of life. We have performed a prospective, randomized, controlled trial to evaluate the effect of placement of an artificial bowel sphincter (Acticon Neosphincter) on continence and quality of life in a group of severely incontinent adults.\n Fourteen adults (male:female, 1:13; age range, 44-75 years) were randomized to placement of the artificial bowel sphincter or to a program of supportive care and were followed for six months from operation or entry into the study. The principal outcome measure was the level of continence, measured with the Cleveland Continence Score, which provides a scale from 0 to 20, representing perfect control through to total incontinence. Secondary outcome measures were perioperative and late complications in the artificial bowel sphincter group, and the changes in quality of life in both groups.\n In the control group, the Cleveland Continence Score was not significantly altered, with an initial value of 17.1 +/- 2.3 and a final value of 14.3 +/- 4.6 at six months. The artificial bowel sphincter group showed a highly significant improvement, changing from 19.0 +/- 1.2 before placement to 4.8 +/- 4.0 at six months after placement. One patient in the artificial bowel sphincter group had failure of healing of the perineal wound and explantation of the device (14 percent explantation rate). There were two other significant perioperative events of recurring fecal impaction initially after placement in one patient and additional suturing of the perineal wound in another. There were major improvements in the quality of life for all measures in the artificial bowel sphincter group. There was significant improvement in all eight subscales of the Medical Outcome Study Short Form-36 measures. The American Medical Systems Quality of Life score was raised from 39 +/- 6 to 83 +/- 14 and the Beck Depression Inventory showed reduction from a level of mild depression (10.8 +/- 9.3) to a normal value (6.8 +/- 8.7). No significant changes in any of the quality of life measures occurred for the control group.\n Through a prospective, randomized trial format, we have shown that placement of an artificial bowel sphincter is safe and effective when compared with supportive care alone. Perioperative and late problems are likely to continue to occur and between 15 percent and 30 percent of patients may require permanent explantation. For the remainder, the device is easy and discrete to use, highly effective in achieving continence, and able to generate a major improvement in the quality of life.", "Severe prolapse may mask potential genuine stress urinary incontinence in women. Some have suggested that a suspending urethropexy be performed in women who have potential genuine stress incontinence demonstrated by barrier reduction of the prolapse preoperatively. Our aim was to compare outcomes after prolapse surgery that included a formal bladder neck suspension with those operations that did not.\n This prospective randomized clinical trial assigned 32 women with bladder neck hypermobility and stage III or IV pelvic organ prolapse to receive either a needle colposuspension or bladder neck endopelvic fascia plication as part of the vaginal reconstructive surgery. Twenty-nine subjects underwent detailed clinical, anatomic, urodynamic, and quality-of-life evaluations before and 6 weeks and 6 months after surgery; 23 completed urinary diary and quality-of-life evaluations after a mean of 2.9 years.\n Needle colposuspension increased short-term complications without providing additional protection from de novo stress incontinence. Barrier testing before surgery predicted urethral sphincteric resistance after surgery; however, such testing neither predicted a patient's function after surgery nor indicated the need for a suspending urethropexy. The combination of a needle colposuspension with a sacrospinous ligament suspension predisposed to the early development of support defects of the upper anterior vaginal segment and to failure of bladder neck support.\n Preoperative barrier testing in women with severe prolapse is not useful in identifying individuals who require a suspending urethropexy. Needle colposuspension increases short-term complications, lacks durability, and may predispose to early and severe recurrent anterior prolapse when performed with a sacrospinous ligament vault suspension.", "The aim of this study was to determine by means of a national database whether higher surgeon caseload correlates with greater utilization of sphincter-sparing procedures than of abdominoperineal resections in treatment of patients with rectal cancer.\n Patients with a primary International Classification of Diseases-9 diagnosis code of rectal cancer who underwent a sphincter-sparing procedure or abdominoperineal resection were selected from the 1997 Nationwide Inpatient Sample, a database that represents 20 percent of all U.S. community hospital discharges. Multivariable logistic regression models were used on a 20 percent sample of this database to estimate the risk-adjusted relationship between surgeon caseload volume and the odds of receiving a sphincter-sparing procedure. All models were adjusted for age, gender, race, hospital region, and patient comorbidity.\n The study population (n = 477) was 70.4 percent white and 57.9 percent male with an average age of 67.6 years. The mean Deyo comorbidity score was 7.0. Patients treated by surgeons in the highest-volume category (> or =10 rectal cancer surgeries per year) compared with those treated by surgeons in the lowest-volume category (1-3 rectal cancer surgeries per year) were significantly more likely to undergo a sphincter-sparing procedure, after adjustment for other covariates (odds ratio = 5.05; 95 percent confidence interval, 2.5-10.22).\n This analysis suggests that rectal cancer patients treated by high-volume surgeons are five times more likely to undergo sphincter-sparing procedures than those treated by low-volume surgeon. This has significant implications for those seeking a sphincter-preserving option for the treatment of their rectal cancer.", "The present study was designed to evaluate functional outcome of perineal repair with and without levatorplasty versus transanal repair of rectocele in obstructed defecation.\n A total of 48 multiparous women with obstructed defecation caused by a rectocele were randomly allocated to three groups: transperineal repair with levatorplasty (TPR-LP; n = 16); transperineal repair without levatorplasty (TPR; n = 16); and transanal repair (TAR; n = 16). The study included defecographic assessment, anal manometry, symptom improvement, sexual function, and score on a function questionnaire. Assessments were done preoperatively and 6 months postoperatively.\n Defecography showed significant reduction in size of rectocele in all groups. Constipation improved significantly in both groups with transperineal repair but not in the group with transanal repair. Significant reductions in mean anal resting pressure, maximum reflex volume, and urge-to-defecate volume were observed only with the transperineal approach (with and without levatorplasty). Functional score improved significantly in the transperineal groups (with levatorplasty, P < 0.001; without levatorplasty, P < 0.01), but not in the transanal group (P = 0.142). Levatorplasty added to transperineal repair significantly improved the overall functional score compared with transperineal repair alone (P < 0.01) and transanal repair TAR (P < 0.001).\n Rectocele repair appears to improve anorectal function by improving rectal urge sensitivity. Transperineal repair of rectocele is superior to transanal repair in both structural and functional outcome. Levatorplasty improves functional outcome, but potential effects on dyspareunia should be discussed with the patient.", "To determine the least invasive surgical procedure by comparing the levels of operative stress hormones, response-reactive protein (CRP) and rest energy expenditure (REE) after laparoscopic (LC) and open cholecystectomy (OC).\n Twenty-six consecutive patients with noncomplicated gallstones were randomized for LC (14) and OC (12). Plasma concentrations of somatotropin, insulin, cortisol and CRP were measured. The levels of REE were determined.\n In the third postoperative day, the insulin levels were lower compared to that before operation (P<0.05). In the first postoperative day, the levels of somatotropin and cortisol were higher in OC than those in LC. After operation the parameters of somatotropin, CRP and cortisol increased, compared to those in the preoperative period in the all patients (P<0.05). In the all-postoperative days, the CRP level was higher in OC than that in LC (7.46+/-0.02; 7.38+/-0.01, P<0.05). After operation the REE level all increased in OC and LC (P<0.05). In the all-postoperative days, the REE level was higher in OC than that in LC (1438.5+/-418.5; 1222.3+/-180.8, P<0.05).\n LC results in less prominent stress response and smaller metabolic interference compared to open surgery. These advantages are beneficial to the restoration of stress hormones, the nitrogen balance, and the energy metabolism. However, LC can also induce acidemia and pulmonary hypoperfusion because of the penumoperitonium it uses during surgery.", "Elective laparoscopic cholecystectomy is established as the treatment of choice for symptomatic cholecystolithiasis and is now proposed for the treatment of acute cholecystitis. The aim of this study is to evaluate biochemical aspects of open (OC) and laparoscopic cholecystectomy (LC). We measured the levels of malondialdehyde (MDA) and the levels of nitrite+nitrate as stable end products of nitric oxide (NO). MDA and nitrite+nitrate levels were increased at both surgical procedures compared to preoperative period, but the rise was more significant in OC than LC. These results showed that both OC and LC caused an increase in oxidative stress. However LC caused significantly less oxidative stress and the changes during surgery returned to preoperative values after LC in a shorter period. The beneficial effects of laparoscopic surgery may be related, partially, to less oxidative stress in the immediate postoperative period.", "Modern sphincter-preserving surgery for ultralow rectal carcinoma has a comparable oncological radicality to abdomino-perineal extirpation (APE). The aim of this study was to assess the long-term morbidity of ultralow anterior resection (ULAR) and its impact on quality of life (QoL) METHODS: The medical records of 142 consecutive patients who underwent surgery for ultralow rectal carcinoma from January 1991 to December 2004 were reviewed retrospectively. The rate of rehospitalisation and rate of non-reversed temporary stomas (\"failure\" stoma) were analysed. Generic and cancer-specific quality of life questionnaires were used to assess quality of life.\n There were a total of 82 ULAR and 60 APE. After ULAR, 25 (30.5%) of the patients were readmitted, stenosis and anastomotic leakage being the main reasons. After APE, only 2 (3.3%) of the patients were readmitted (P < 0.001). The rate of patients with a permanent stoma after sphincter-saving surgery was 22.0%. The failure rate was higher for older patients (P = 0.005) and for coloanal pull-through anastomosis (P = 0.001). The exploratory analysis revealed a negative impact of a \"failure\" stoma on QoL.\n Severe long-term morbidity and high failure rate of stoma reversal have a significantly worse impact on QoL after ULAR; therefore, APE is a valid alternative to ULAR, especially in elder patients with planned coloanal pull-through anastomosis.", "The aim of this retrospective study was to compare the functional and clinical results of laparoscopic rectopexy with those of the open technique in two similar groups of patients with complete rectal prolapse and fecal incontinence. Between November 1992 and June 1997, 21 patients underwent abdominal rectopexy. Thirteen patients (group A: 12 women and 1 man, mean age 52.9 years, range 28-70) and 8 patients (group B: 8 women, mean age 58.2 years, range 20-76) were submitted to Well's rectopexy by the open technique and the laparoscopic approach, respectively, without division of the lateral rectal ligaments. Assignment to each group was done randomly. Before the operation, a detailed clinical history was taken, and patients were studied with inspection and digital examination of the anorectum, proctosigmoidoscopy, determination of pancolonic transit time, dynamic defecography, anorectal manometry, and anal electromyography. After the operation, all patients underwent perineal physiotherapy, external electric stimulation, and perineal biofeedback. The mean follow-up time was 29.5 months (range 6-54) in group A and 25.7 months (range 8-45) in group B. Values were compared by chi-square, Mann-Whitney U, and Wilcoxon tests, as appropriate; differences were considered significant at p < 0.05. In both groups, dyschezia and fecal incontinence improved significantly (p < 0.05) after the operation. Basal pressure of anal sphincter, squeezing pressure, and rectoanal reflex improved without significance, whereas anoperineal pain was not significantly reduced. In group B, the postoperative hospital stay was shorter than in group A, with a marked reduction of costs. Laparoscopic Well's rectopexy has the same clinical and functional results as the open technique, with a shorter postoperative hospital stay and lower costs.", "The purpose of this study was to compare intra-anal electromyographic biofeedback alone with intra-anal biofeedback that was augmented with electrical stimulation of the anal sphincter in the treatment of postpartum fecal incontinence. A secondary aim was to examine the impact of the treatment on continence-related quality of life.\n Sixty symptomatic women were assigned randomly to receive intra-anal electromyographic biofeedback or electrical stimulation of the anal sphincter once weekly for 12 weeks and to perform daily pelvic floor exercises between treatments. Therapeutic response was evaluated with a symptom questionnaire to determine continence score, anal manometry, and endoanal ultrasound scanning. Quality of life was assessed before and after treatment with a validated questionnaire.\n Fifty-four women completed the treatment; 52 women (96%) had ultrasonic evidence of an external anal sphincter defect. After the treatment, both groups demonstrated significant improvement in continence score (P < .001) and in squeeze anal pressures (P < .04). Resting anal pressures did not alter significantly. Quality of life improved after the completion of physiotherapy, but there were no differences in outcome between intra-anal electromyographic biofeedback and electrical stimulation of the anal sphincter.\n Intra-anal electromyographic biofeedback therapy was associated with improved continence and quality of life in women with altered fecal continence after delivery. The addition of electrical stimulation of the anal sphincter did not enhance symptomatic outcome." ]	Optimal PRT improves LR, OA mortality, but no increase in sphincter sparing procedure. CRT further increases local control. If the objective is to increase the incidence of sphincter sparing surgery, endocavitary boost showed the most promise. Strategies with the potential to improve outcomes, especially OAS and spincter sparing while reducing acute and late toxicities (rectal and sexual function) are needed to guide future strategy designs.
CD001236	[ "16536100", "18021143" ]	[ "Randomised controlled trial of perineal shaving versus hair cutting in parturients on admission in labor.", "Perineal outcomes and maternal comfort related to the application of perineal warm packs in the second stage of labor: a randomized controlled trial." ]	[ "To compare the maternal and neonatal outcomes between perineal shaving and hair cutting in parturients on admission in labor\n Five hundred pregnant women with labor pain and no medical or obstetric complications were selected at random on admission to be assigned into two groups at Rajavithi Hospital from 1st November 2001 to 28th February 2002. Forty two women were excluded because of cesarean section. Two hundred and twenty-seven cases received perineal hair cutting and 231 cases received perineal shaving.\n The gestational age at delivery was statistically significant difference between those receiving perineal hair cutting (39.4 week) comparing with those receiving perineal shaving (39.1 week) (p < 0.05). There was no statistically significant difference in 2 groups for puerperal morbidity, perineal wound infection and dehiscence. There were no neonatal infection and puerperal infection in both groups, where as both accoucheurs and perineorrhaphy operators were more satisfied the perineal shaving group than the cutting group (p < 0.001).\n Perineal shaving or hair cutting on admission in labor had no statistical significant difference effect on the perineal wound infection and dehiscence, neonatal infection, puerperal morbidity and infection.", "Perineal warm packs are widely used during childbirth in the belief that they reduce perineal trauma and increase comfort during late second stage of labor. The aim of this study was to determine the effects of applying warm packs to the perineum on perineal trauma and maternal comfort during the late second stage of labor.\n A randomized controlled trial was undertaken. In the late second stage of labor, nulliparous women (n = 717) giving birth were randomly allocated to have warm packs (n = 360) applied to their perineum or to receive standard care (n = 357). Standard care was defined as any second-stage practice carried out by midwives that did not include the application of warm packs to the perineum. Analysis was on an intention-to-treat basis, and the primary outcome measures were requirement for perineal suturing and maternal comfort.\n The difference in the number of women who required suturing after birth was not significant. Women in the warm pack group had significantly fewer third- and fourth-degree tears and they had significantly lower perineal pain scores when giving birth and on \"day 1\" and \"day 2\" after the birth compared with the standard care group. At 3 months, they were significantly less likely to have urinary incontinence compared with women in the standard care group.\n The application of perineal warm packs in late second stage does not reduce the likelihood of nulliparous women requiring perineal suturing but significantly reduces third- and fourth-degree lacerations, pain during the birth and on days 1 and 2, and urinary incontinence. This simple, inexpensive practice should be incorporated into second stage labor care." ]	There is insufficient evidence to recommend perineal shaving for women on admission in labour.
CD006767	[ "17592075", "16672699", "15234692", "12618680", "16408299", "10811511", "17932898", "12934762" ]	[ "Nitinol stent implantation versus percutaneous transluminal angioplasty in superficial femoral artery lesions up to 10 cm in length: the femoral artery stenting trial (FAST).", "Balloon angioplasty versus implantation of nitinol stents in the superficial femoral artery.", "Angioplasty or bypass for superficial femoral artery disease? A randomised controlled trial.", "Systematic versus selective stent placement after superficial femoral artery balloon angioplasty: a multicenter prospective randomized study.", "Functional and clinical outcomes of nitinol stenting with and without abciximab for complex superficial femoral artery disease: a randomized trial.", "Percutaneous transluminal angioplasty with or without stenting for femoropopliteal occlusions? A randomized controlled study.", "Randomized, double-blind, multicenter study of the polymer-based 17-beta estradiol-eluting stent for treatment of native coronary artery lesions: six-month results of the ETHOS I trial.", "Coronary stenting after rotational atherectomy in diffuse lesions of the small coronary artery: comparison with balloon angioplasty before stenting." ]	[ "Endoluminal treatment of superficial femoral artery lesions is a matter of controversy. The present study was designed to investigate the impact of nitinol stenting of superficial femoral artery lesions with a maximum length of 10 cm on restenosis and clinical outcomes at 1 year.\n Two hundred forty-four patients (168 men; 66+/-9 years) with a single superficial femoral artery lesion and chronic limb ischemia were randomized to implantation of a single Bard Luminexx 3 stent (123 patients) or stand-alone percutaneous transluminal angioplasty (PTA) (121 patients). Mean lesion length was 45 mm. Technical success (residual stenosis <50% for PTA, <30% for stenting) was achieved in 96 patients assigned to PTA (79%) and 117 patients assigned to stenting (95%); 13 PTA group patients (11%) \"crossed over\" to stenting. At 1 year, the primary end point of ultrasound-assessed binary restenosis was reached in 39 of 101 PTA group patients (38.6%) and 32 of 101 stent group patients (31.7%; absolute treatment difference, -6.9%; 95% CI, -19.7% to 6.2%; P=0.377). Target lesion revascularization rates at 1 year were 18.3% and 14.9%, respectively (absolute treatment difference, -3.3%; 95% CI, -13.0% to 6.4%; P=0.595). No statistically significant difference between treatment groups was observed at 12 months in the improvement by at least 1 Rutherford category of peripheral arterial disease.\n In the present study of patients with short superficial femoral artery lesions, the hypothesized absolute difference of 20% in binary restenosis at 1 year between the implantation of a single Luminexx nitinol stent and stand-alone PTA could not be demonstrated. A smaller difference requiring a larger trial might have been missed.", "Because stent implantation for disease of the superficial femoral artery has been associated with high rates of late clinical failure, percutaneous transluminal angioplasty is preferred for endovascular treatment, and stenting is recommended only in the event of suboptimal technical results. We evaluated whether primary implantation of a self-expanding nitinol (nickel-titanium) stent yielded anatomical and clinical benefits superior to those afforded by percutaneous transluminal angioplasty with optional secondary stenting.\n We randomly assigned 104 patients who had severe claudication or chronic limb ischemia due to stenosis or occlusion of the superficial femoral artery to undergo primary stent implantation (51 patients) or angioplasty (53 patients). Restenosis and clinical outcomes were assessed at 6 and 12 months.\n The mean (+/-SD) length of the treated segment was 132+/-71 mm in the stent group and 127+/-55 mm in the angioplasty group. Secondary stenting was performed in 17 of 53 patients (32 percent) in the angioplasty group, in most cases because of a suboptimal result after angioplasty. At 6 months, the rate of restenosis on angiography was 24 percent in the stent group and 43 percent in the angioplasty group (P=0.05); at 12 months the rates on duplex ultrasonography were 37 percent and 63 percent, respectively (P=0.01). Patients in the stent group were able to walk significantly farther on a treadmill at 6 and 12 months than those in the angioplasty group.\n In the intermediate term, treatment of superficial-femoral-artery disease by primary implantation of a self-expanding nitinol stent yielded results that were superior to those with the currently recommended approach of balloon angioplasty with optional secondary stenting. (ClinicalTrials.gov number, NCT00281060.).\n Copyright 2006 Massachusetts Medical Society.", "To evaluate whether angioplasty or above-knee bypass is the best treatment for symptomatic superficial femoral artery occlusive lesions, we performed a multicentre randomised trial.\n Between October 1995 and August 1998, 56 patients were enrolled, all with symptoms related to a 5-15 cm long occlusive lesion of the superficial femoral artery. Thirty-one patients were randomly assigned to percutaneous transluminal angioplasty (PTA); 25 patients to bypass surgery. All patients were followed at 1, 6 and 12 months after the procedure. The primary outcome of our study was re-occlusion of the femoral artery.\n Thirty patients underwent the allocated PTA and 24 patients underwent bypass surgery. Cumulative 1-year primary patency after PTA was 43 and 82% after bypass surgery. After PTA more than half of the patients had a re-occlusion with an absolute risk reduction of 31% (CI: 6-56%) in favour of bypass surgery. The hazard ratio for occlusion comparing PTA with bypass surgery is 2.24 (95% CI: 0.9-5.58).\n Despite 18 participating centres only 56 patients were randomised to PTA our bypass surgery. Based on our results, for every three patients treated with bypass surgery instead of PTA, one additional re-occlusion is prevented. Therefore, we conclude that with respect to patency, for long superficial femoral artery (SFA) stenoses or occlusions, surgery is better than PTA.", "Outcome with selective or systematic stenting with the Palmaz vascular stent was compared in patients with limb-threatening ischemia or persistent disabling claudication despite medical therapy, with less than 7 cm stenosis or occlusion of the superficial femoral artery.\n This was a multicenter prospective randomized trial with centralized allocation of treatment and independent review of vascular events. The primary end point was presence of more than 50% stenosis at 1-year angiographic follow-up. Secondary end points were survival; occurrence of vascular events in the treated leg; and number of failed procedures, defined as more than 50% stenosis or death at 1 year.\n Two hundred twenty-seven patients were enrolled in the study, 112 in the selective stent group, and 115 in the systematic stent group. Seventeen patients (15%) in the selective stent group received a stent after suboptimal results of percutaneous transluminal angioplasty. Angiograms for 140 patients were available at 1-year follow-up and demonstrated no statistical difference between the two groups; more than 50% stenosis of the dilated site was noted in 21 of 65 patients (32,3%) in the selective stent group and 26 of 75 patients (34.7%) in the systematic stent group (P =.85, Fisher exact test). Survival in the percutaneous transluminal angioplasty and stent groups was, respectively, 92% and 96% at 1 year, 89% and 93% at 2 years, and 82% and 80% at 4 years (P =.40, log-rank test). Survival free of new vascular events in the treated limb was 77% and 65% at 1 year, 70% and 53% at 2 years, and 57% and 44% at 4 years (P =.017, log-rank test). Number of failed procedures at 1 year was 29 of 86 (33%) and 30 of 89 (34%) (P = 0.9).\n Systematic stenting of short stenosis or occlusion of the superficial femoral artery is not justified. Palmaz vascular stent placement should be reserved for use in patients with suboptimal results of balloon angioplasty.", "To evaluate the effect of glycoprotein IIb/IIIa inhibition during nitinol stenting, of superficial femoral occlusive disease.\n Stent implantation in the superficial femoral artery has been associated with suboptimal results while Glycoprotein IIb/IIIa inhibitors have shown improved procedural results during coronary intervention. We evaluated abciximab infusion during (Smart Stent) implantation in superficial femoral obstructions.\n We conducted a randomized placebo controlled trial. The two primary end points include: (1) 9-month restenosis defined as a decrease in ankle brachial index and in-stent duplex ultrasound restenosis: (2) adverse events defined as death (30 days) or repeat revascularization within 9 months.\n Twenty-seven patients were randomized to abciximab and 24 patients to control (placebo). The primary end point of cumulative restenosis occurred in 15.4% of patients administered abciximab and in 12% administered placebo (P = 0.873). The primary restenosis endpoint in diabetics and total occlusions were similar at 14.3% and 15.4% respectively. The composite end point of 30-day mortality and 9-month revascularization occurred in 5.8% abciximab and 0% (P = 0.274) placebo with no 30-day deaths. Graded treadmill time and Rutherford class were all significantly improved in both groups, but the abciximab group did not appear to demonstrate any identifiable effect.\n (Smart Stent) nitinol stenting of the superficial femoral artery was associated with favorable functional outcomes at 9 months. Adjunctive abciximab did not appear to demonstrate any identifiable effect.\n 2006 Wiley-Liss, Inc.", "To investigate the-one year outcome of PTA and stenting and PTA alone for femoropopliteal occlusions.\n Randomized prospective study\n 32 patients with femoropopliteal occlusions were randomized into two treatment groups: PTA and Strecker-stent (n=15) and PTA alone (n=17). The median age of the patients was 71 years. All patients had chronic limb ischaemia, 66% had tissue loss, 19% had rest pain and 15% had disabling claudication. The median ABPI was 0.45. The occlusion was confined to the superficial femoral artery in 30 cases and to the popliteal artery in 2 cases. The median length of the occlusions was 7.3 cm. Aspirin (ASA), 160 mg daily, was administrated postoperatively but no anticoagulation was used. The follow-up included: clinical examination, measurement of ABPI and control angiography at 12 months or earlier when necessary (20 patients).\n There was no mortality or limb loss as a consequence of the treatment. There were six (16%) immediate major complications in five patients. In the PTA group, one patient had a myocardial infarction and three patients needed arteriography due to bleeding. In the stent group, one patient required arteriography and embolectomy. The one-year mortality was 6% and there were no amputations. Four patients (two in each group) were operated on with a femorodistal bypass. The rate of clinical improvement was 71% after PTA and stent and 60% after PTA alone (p=0.17). An increased ABPI (>0.10) was shown in 50% of the stent group and 61% in the PTA group (p=0.17). Angiographic re-occlusions were seen in 33% and 75% in the stent and PTA groups respectively (p=0.17), while the rate of restenosis was significantly higher in the stent group (50% vs 25%) (p=0.033).\n Stenting following PTA for femoropopliteal occlusions does not significantly improve neither the clinical state nor the clinical/angiographic patency. The results do not justify any routine placement of stent following PTA in the successfully recanalized femoropopliteal arteries. The low rate of acceptance of a follow-up angiography indicates that this kind of study should preferably use duplex scanning instead of angiography for follow-up.", "The ETHOS I trial was the first in-human experience evaluating the safety and efficacy of two different release formulations of the 17-beta estradiol-eluting R-Stent versus uncoated control stents for the treatment of patients with single de novo native coronary lesions.\n Estrogens were reported to inhibit neointimal proliferation and to accelerate endothelial regeneration after coronary angioplasty and thus could be an ideal compound to deliver on a stent for the purpose of reducing in-stent restenosis.\n Ninety-five patients were randomized to receive a slow-release (n = 32) or the moderate release (n = 31) formulations or the bare metal stent (n = 32). The primary end point was the 6-month percent in-stent volume obstruction by intravascular ultrasound (IVUS).\n Diabetes was present in 29.5% of patients; the mean reference vessel diameter was 2.90 mm; and the mean lesion length was 13.5 mm. Primary endpoint, 6-month percent in-stent volume obstruction by IVUS, did not differ significantly between the 3 groups (31% +/- 14%, 33% +/- 11%, and 31% +/- 14%, P = 0.83). Secondary endpoints also did not differ significantly between the groups including 6-month rates of in-lesion binary angiographic restenosis (13.3%, 14.3%, and 12.5%, P = 0.98), in-stent late loss (0.82 +/- 0.49 mm, 0.86 +/- 0.53 mm, and 0.84 +/- 0.46 mm, P = 0.97), target lesion revascularization (12.5%, 6.9%, and 6.5%, P = 0.64), and major adverse cardiac events (18.8%, 10.3%, and 6.5%, P = 0.31).\n In this first-in-man randomized trial, the 17-beta estradiol-eluting R-Stent, in either slow- or moderate-release formulations, was well-tolerated, but showed no benefit for treatment of coronary lesions when compared to controls.\n (c) 2007 Wiley-Liss, Inc.", "The purpose of this randomized trial was to evaluate the role of debulking and balloon predilation on acute and long-term results of stent implantation in diffuse stenosis of small vessels. Patients with symptomatic diffuse stenosis of the native left anterior descending coronary artery between 2 and 2.9 mm in size were randomly assigned to rotational atherectomy (group I, n = 21) or balloon dilation (group II, n = 20) before stenting. The primary end point of the study was the incidence of angiographic restenosis at follow-up; adverse clinical events, such as death, myocardial infarction, stroke, or target vessel revascularization, were assessed as secondary end points. Acute gain was significantly greater in group I than in group II (p = 0.038), but net gain at follow-up was similar in both groups (p = 0.24). There was no significant difference in angiographic restenosis rate (33.3% vs 31.3%, p = 0.80), target vessel revascularization (23.8% vs 15%, p = 0.21) or 1-year event-free survival rate (72.8% vs 84.6%, p = 0.28). In conclusion, rotational atherectomy before stenting showed no additional benefit over balloon dilation with stenting in the management of diffuse lesions in small coronary vessels." ]	There is limited benefit to stenting lesions of the superficial femoral artery in addition to angioplasty, however this cannot be recommended routinely based on the results of this analysis.
CD003052	[ "1761665", "7635364" ]	[ "The ESHRE multicentre trial on the treatment of unexplained infertility: a preliminary report. European Society of Human Reproduction and Embryology.", "Fallopian tube sperm perfusion has no advantage over intra-uterine insemination when used in combination with ovarian stimulation for the treatment of unexplained infertility." ]	[ "Nineteen European fertility centres participated in a controlled randomized trial aimed at comparing the effectiveness of five methods for the treatment of unexplained infertility. Each centre was invited to employ two of the five treatments being investigated, and the treatment allocated to individual patients was then decided by randomization. The treatments were superovulation alone, and superovulation together with one of the following procedures: intra-uterine insemination (IUI), intra-peritoneal insemination (IPI), gamete intra-Fallopian transfer (GIFT), in-vitro fertilization (IVF). All the patients admitted to the study had experienced greater than 36 months infertility prior to the start of the trial, and only patients less than 38 years of age were included in the investigation. Further, the study was confined to patients with normal Fallopian tubes, and where there was evidence of spontaneous ovulation. Yet another prerequisite for inclusion in the study was that the male partner was 'normal' as regards fertility. Due to unavoidable practical difficulties, the experimental design eventually obtained was severely unbalanced. Nevertheless, objective statistical comparisons were possible among the five treatments, using non-orthogonal analyses of variance. By the completion of the trial 444 patients had been treated in a total of 649 cycles. There was some statistical evidence that the pregnancy rate obtained from superovulation alone was inferior to that obtained by using superovulation together with one of the methods of assisted conception.(ABSTRACT TRUNCATED AT 250 WORDS)", "In this prospective randomized study we treated 60 couples with unexplained infertility with a combination of ovarian stimulation and either intrauterine insemination (IUI) or fallopian sperm perfusion (FSP). In the IUI we used a volume of 0.5 ml of inseminate and in the FSP a volume of 4 ml. The demographic characteristics of the patients, the stimulation parameters and the sperm data were not statistically different between the two groups. The pregnancy rate per cycle was 16.2% in the IUI group and 14.5% in the FSP group and the pregnancy rate per woman was 40 and 36.7%, respectively (not statistically different). We conclude that IUI and FSP are equally effective in the treatment of couples with unexplained infertility." ]	There is insufficient evidence to suggest that oral agents are inferior or superior to injectable agents in the treatment of unexplained subfertility. Information on harms is sketchy, and remains compatible with large differences in either direction. Much larger trials than have previously been undertaken are required to provide information on relative harms as well as benefits.
CD006185	[ "17213237", "12468788", "19627940", "17023237", "7041850", "9349677", "3288172", "11594641", "12235606", "8202978", "11228945" ]	[ "Repetitive locomotor training and physiotherapy improve walking and basic activities of daily living after stroke: a single-blind, randomized multicentre trial (DEutsche GAngtrainerStudie, DEGAS).", "Treadmill training with partial body weight support and an electromechanical gait trainer for restoration of gait in subacute stroke patients: a randomized crossover study.", "The effectiveness of locomotor therapy using robotic-assisted gait training in subacute stroke patients: a randomized controlled trial.", "Effectiveness of gait training using an electromechanical gait trainer, with and without functional electric stimulation, in subacute stroke: a randomized controlled trial.", "Electromyographic feedback in the remobilization of stroke patients: a controlled trial.", "Rhythmic facilitation of gait training in hemiparetic stroke rehabilitation.", "Biofeedback and functional electric stimulation in stroke rehabilitation.", "Walking training of patients with hemiparesis at an early stage after stroke: a comparison of walking training on a treadmill with body weight support and walking training on the ground.", "Gait outcomes after acute stroke rehabilitation with supported treadmill ambulation training: a randomized controlled pilot study.", "Rehabilitation of walking with electromyographic biofeedback in foot-drop after stroke.", "Comparison of partial body weight-supported treadmill gait training versus aggressive bracing assisted walking post stroke." ]	[ "To evaluate the effect of repetitive locomotor training on an electromechanical gait trainer plus physiotherapy in subacute stroke patients.\n Randomized controlled trial.\n Four German neurological rehabilitation centres.\n One hundred and fifty-five non-ambulatory patients (first-time stroke <60 days).\n Group A received 20 min locomotor training and 25 min physiotherapy; group B had 45 min physiotherapy every week day for four weeks.\n Primary variables were gait ability (Functional Ambulation Category, 0-5) and the Barthel Index (0-100), blindly assessed at study onset, end, and six months later for follow-up. Responders to the therapy had to become ambulatory (Functional Ambulation Category 4 or 5) or reach a Barthel Index of > or = 75. Secondary variables were walking velocity, endurance, mobility and leg power.\n The intention-to-treat analysis revealed that significantly greater number of patients in group A could walk independently: 41 of 77 versus 17 of 78 in group B (P B < 0.0001) at treatment end. Also, significantly more group A patients had reached a Barthel Index > or = 75: 44 of 77 versus 21 of 78 (P B < 0.0001). At six-month follow-up, the superior gait ability in group A persisted (54 of 77 versus 28 of 78, P B < 0.0001), while the Barthel Index responder rate did not differ. For all secondary variables, group A patients had improved significantly more (P B < 0.0001) during the treatment period, but not during follow-up.\n Intensive locomotor training plus physiotherapy resulted in a significantly better gait ability and daily living competence in subacute stroke patients compared with physiotherapy alone.", "The purpose of this study was to compare treadmill and electromechanical gait trainer therapy in subacute, nonambulatory stroke survivors. The gait trainer was designed to provide nonambulatory subjects the repetitive practice of a gait-like movement without overexerting therapists.\n This was a randomized, controlled study with a crossover design following an A-B-A versus a B-A-B pattern. A consisted of 2 weeks of gait trainer therapy, and B consisted of 2 weeks of treadmill therapy. Thirty nonambulatory hemiparetic patients, 4 to 12 weeks after stroke, were randomly assigned to 1 of the 2 groups receiving locomotor therapy every workday for 15 to 20 minutes for 6 weeks. Weekly gait ability (functional ambulation category [FAC]), gait velocity, and the required physical assistance during both kinds of locomotor therapy were the primary outcome measures, and other motor functions (Rivermead motor assessment score) and ankle spasticity (modified Ashworth score) were the secondary outcome measures. Follow-up occurred 6 months later.\n The groups did not differ at study onset with respect to the clinical characteristics and effector variables. During treatment, the FAC, gait velocity, and Rivermead scores improved in both groups, and ankle spasticity did not change. Median FAC level was 4 (3 to 4) in group A compared with 3 (2 to 3) in group B at the end of treatment (P=0.018), but the difference at 6-month follow up was not significant. The therapeutic effort was less on the gait trainer, with 1 instead of 2 therapists assisting the patient at study onset. All but seven patients preferred the gait trainer.\n The newly developed gait trainer was at least as effective as treadmill therapy with partial body weight support while requiring less input from the therapist. Further studies are warranted.", "To evaluate the effectiveness of early and prolonged locomotor treatment with the use of a robotic-assisted gait training (RAGT) device (Lokomat; Hocoma Inc., Zurich, Switzerland) on the functional outcomes of patients after subacute stroke.\n A nonblinded prospective, randomized, controlled study.\n Rehabilitation department in tertiary university medical center.\n Sixty-seven patients in the first 3 months after subacute stroke were randomized into 2 groups as follows. Thirty-seven patients were treated with RAGT, and 30 were treated with regular physiotherapy. Inclusion criteria were first stroke, independent ambulation before the stroke, and neurological severity between 6 and 20 according to the National Institutes of Health Stroke Scale (NIHSS).\n RAGT treatment was administered 3 times a week for 30 minutes, combined with regular physiotherapy for 6 weeks. Control patients received the equivalent additional time of regular physiotherapy.\n The primary outcome was the ability to walk independently, as assessed by use of the functional ambulatory capacity scale. The secondary outcomes included the neurological status according to the NIHSS; functional motor assessment (determined by use of the stroke activity scale); and gait parameters, including gait velocity, endurance, and number of climbed stairs.\n In the intention-to-treat analysis, subjects in the RAGT group exhibited greater gains than the control group in their ability to walk independently, as expressed by a greater functional ambulatory capacity score (P < .01), and in their neurological status according to NIHSS (P < .01). Among those who achieved independent walking, nonsignificant differences between groups were noted according to secondary outcome measures of gait parameters except from step climbing.\n This controlled study showed, at the end of a 6-week trial, that locomotor therapy with the use of RAGT combined with regular physiotherapy produced promising effects on functional and motor outcomes in patients after subacute stroke as compared with regular physiotherapy alone.", "To compare the therapeutic effects of conventional gait training (CGT), gait training using an electromechanical gait trainer (EGT), and gait training using an electromechanical gait trainer with functional electric stimulation (EGT-FES) in people with subacute stroke.\n Nonblinded randomized controlled trial.\n Rehabilitation hospital for adults.\n Fifty patients were recruited within 6 weeks after stroke onset; 46 of these completed the 4-week training period.\n Participants were randomly assigned to 1 of 3 gait intervention groups: CGT, EGT, or EGT-FES. The experimental intervention was a 20-minute session per day, 5 days a week (weekdays) for 4 weeks. In addition, all participants received their 40-minute sessions of regular physical therapy every weekday as part of their treatment by the hospital.\n Five-meter walking speed test, Elderly Mobility Scale (EMS), Berg Balance Scale, Functional Ambulatory Category (FAC), Motricity Index leg subscale, FIM instrument score, and Barthel Index.\n The EGT and EGT-FES groups had statistically significantly more improvement than the CGT group in the 5-m walking speed test (CGT vs EGT, P=.011; CGT vs EGT-FES, P=.001), Motricity Index (CGT vs EGT-FES, P=.011), EMS (CGT vs EGT, P=.006; CGT vs EGT-FES, P=.009), and FAC (CGT vs EGT, P=.005; CGT vs EGT-FES, P=.002) after the 4 weeks of training. No statistically significant differences were found between the EGT and EGT-FES groups in all outcome measures.\n In this sample with subacute stroke, participants who trained on the electromechanical gait trainer with body-weight support, with or without FES, had a faster gait, better mobility, and improvement in functional ambulation than participants who underwent conventional gait training. Future studies with assessor blinding and larger sample sizes are warranted.", "Electromyographic biofeedback was compared with simple exercise therapy as to its effectiveness in improving foot-drop in 22 stroke patients. The study was designed to be a rigorous trial of biofeedback and the patients tested were aged and had stroke of long duration. One group of 11 patients underwent 6 weeks of exercise therapy 2 sessions per week for 15 minutes per session; the 2nd group of 11 patients underwent similar therapy with EMG feedback. All therapy was conducted by a research assistant who was not a trained therapist. The groups were assessed blind before treatment, after treatment and a 6-week follow-up. The significantly greater improvements in the biofeedback group in terms of muscle strength at the end of treatment were maintained at follow-up. On the range of movement and gait analysis measures, both groups showed some improvement after treatment. However, at follow-up this improvement had relapsed for the exercise group while for the biofeedback group it had been maintained. It is argued that controlled trials are possible in biofeedback and that using patients as their own controls is not justified in view of the present findings and the previously reported literature.", "Experimental and control groups of 10 hemiparetic stroke patients each underwent a 6 week, twice daily gait training program. The control group participated in a conventional physical therapy gait program. The experimental group trained in the same basic program with the addition of rhythmic auditory stimulation (RAS). Patients entered the study as soon as they could complete 5 strides with hand-held assistance. The training program had to be completed within 3 months of the patients' stroke. In the experimental group RAS was used as a timekeeper to synchronize step patterns and gradually entrain higher stride frequencies. Study groups were equated by gender, lesion site, and age. Motor function was assessed at pretest using Barthel, Fugl-Meyer, and Berg Scales. Walking patterns were assessed during pre- and post-test without RAS present. Pre- vs post-test measures revealed a statistically significant (P<0.05) increase in velocity (164% vs 107%), stride length (88% vs 34%), and reduction in EMG amplitude variability of the gastrocnemius muscle (69% vs 33%) for the RAS-training group compared to the control group. The difference in stride symmetry improvement (32% in the RAS-group vs 16% in the control group) was statistically not significant. The data offer evidence that RAS is an efficient tool to enhance efforts in gait rehabilitation with acute stroke patients.", "The study examined the efficacy of functional electric stimulation (FES) and biofeedback (BFB) treatment of gait dysfunction in patients with hemiplegia after stroke. These two therapeutic modalities were tested alone and in combination in a prospective, controlled, randomized trial. The authors hypothesized that in concurrent use, these two modalities would complement one another. Thirty-six hemiplegic patients undergoing rehabilitation after stroke were accepted for study and randomized into four groups to receive either control, FES, BFB, or combined therapies. Each patient received 30 minutes of treatment three times per week for six weeks, in addition to their general rehabilitation program. Quantitative gait analysis was performed biweekly on each subject during the experimental therapy and for four weeks afterward. Thirty-two subjects completed the study. Combined therapy with BFB and FES resulted in improvements in both knee and ankle minimum flexion angles during swing phase that were statistically significant with p = 0.05 and p = 0.02, respectively. Velocity of gait, cycle time, and symmetry of stance phases also improved. The length of time elapsed since the stroke did not prove to be a significant factor.", "To compare the effect of walking training on a treadmill with body weight support (BWS) and walking training on the ground at an early stage of rehabilitation in patients with hemiparesis after stroke.\n Randomized controlled experimental study.\n Multicentre design; three departments of rehabilitation medicine.\n Seventy-three consecutive first stroke patients admitted to a rehabilitation clinic were randomized into a treatment group and a control group.\n The treatment group received walking training on a treadmill with BWS for 30 minutes, 5 days a week. The control group received walking training according to the Motor Relearning Programme (MRP) on the ground for 30 minutes 5 days a week, not including treadmill training. During the time in the rehabilitation department (about two months), all patients in the study also received professional stroke rehabilitation besides the walking training in the two groups.\n Functional Independence Measure (FIM), walking velocity for 10 m, Functional Ambulation Classification (FAC), Fugl-Meyer Stroke Assessment and Berg's Balance Scale. The assessments were performed at admission, at discharge and at 10-month follow-up.\n There were no statistically significant differences between the groups at discharge or at the 10-month follow-up with regard to FIM, walking velocity, FAC, Fugl-Meyer Stroke Assessment, and Berg's Balance Scale. Patients in both groups improved in these variables from admission to the 10-month follow-up.\n Treadmill training with BWS at an early stage of rehabilitation after stroke is a comparable choice to walking training on the ground.", "To investigate gait outcomes with supported treadmill ambulation training (STAT) associated with regular rehabilitation in acute stroke survivors.\n Randomized controlled trial, pilot study.\n Rehabilitation medicine service at a Veterans Affairs medical center.\n Seven acute stroke survivors assigned to regular intervention group and 6 patients assigned to STAT intervention.\n Regular intervention consisted of 3 hours daily of physical therapy, kinesiotherapy, and occupational therapy. STAT group received regular rehabilitation with STAT substituted for usual gait training. Participants were tested at baseline, treated for an average of 3 weeks, and retested on discharge. The analysis of covariance procedure was used to test for differences between the 2 approaches.\n Functional Ambulation Category Scale, gait speed, walking distance, gait energy expenditure, and gait energy cost.\n The small sample size did not generate enough power to detect significant differences in any variable. However, medium to large effect sizes of 0.7 and 1.16 standard deviation units were observed for gait energy cost and walk distance, respectively.\n This pilot study indicated that STAT is a safe, feasible, and promising intervention for acute stroke survivors. A larger trial is warranted for statistical relevance.", "Alterations of gait cycle and foot-drop on the paretic limb are characteristic of stroke patients. Electromyographic biofeedback treatment has been used in rehabilitation of walking, but results are controversial. We performed gait analysis to evaluate the efficacy of electromyographic biofeedback compared with physical therapy.\n Sixteen patients with ischemic stroke were enrolled in the study. The experimental group (4 men, 4 women) received electromyographic biofeedback treatment together with physical therapy. The control group (5 men, 3 women) was treated with physical therapy only. Clinical and functional evaluations before and after treatment were performed using Canadian Neurological, Adams, Ashworth, Basmajian, and Barthel Index scales. Computerized gait analysis was performed in all patients.\n Electromyographic biofeedback patients showed significantly increased scores on the Adams scale (P < .05) and Basmajian scale (P < .01). Gait analysis in this group showed a recovery of foot-drop in the swing phase (P < .02) after training.\n Our data confirm that the electromyographic biofeedback technique increases muscle strength and improves recovery of functional locomotion in patients with hemiparesis and foot-drop after cerebral ischemia.", "To test the hypothesis that partial body weight-supported treadmill training (PBWSTT) provides more effective gait training than an equally supportive but less physiologic aggressive bracing assisted walking (ABAW) program.\n Following informed consent, patients participating in an inpatient rehabilitation program with significant leg weakness and need for at least moderate assistance for walking, without orthostatic hypotension, symptomatic dyspnea, or angina pectoris were randomized to receive PBWSTT vs. ABAW. PBWSTT was provided by a commercially available, overhead motorized hoist attached to a parachute-type body harness, which provided partial support of the patient's weight over a treadmill. Therapists assisted with weight shifting, leg advancement, and foot placement as needed. ABAW included aggressive early therapist-assisted ambulation using knee-ankle combination bracing and hemi-bar if needed. Treatment sessions of up to 45 minutes per day, five days per week were given as tolerated for the duration of the inpatient stay or until patients could walk over-ground unassisted. All patients had an additional 45-minute session of functionally oriented physical therapy each day with or without bracing as judged appropriate by the patient's individual therapist.\n Fifty-six patients a mean age of 71 +/- 1 SEM were enrolled 40 +/- 3 days post stroke. Although the outcome of the two groups as a whole did not differ, a subgroup with major hemispheric stroke defined by the presence of hemiparesis, hemianopic visual deficit, and hemihypesthesia who received more than 12 treatment sessions showed significantly better over-ground endurance (90 +/- 34 vs. 44 +/- 10 meters) and speed scores (12 +/- 4 vs. 8 +/- 2 meters/minute) for PBWSTT vs. ABAW, respectively.\n PBWSTT and ABAW are equally effective gait training techniques except for a subset of patients with major hemispheric stroke who are difficult to mobilize using ABAW alone." ]	Patients who receive electromechanical-assisted gait training in combination with physiotherapy after stroke are more likely to achieve independent walking than patients receiving gait training without these devices. However, further research should address specific questions, for example what frequency or duration of electromechanical-assisted gait training might be most effective and at what time after stroke. Follow-up studies are also needed to find out how long the benefit lasts.
CD006896	[ "15787886", "5460838", "1489222", "7297938", "6658501", "6786536", "15846191", "16210715", "11247198", "18996930", "16137113", "563620", "538502", "7979565", "5641006", "525266", "14297280", "1263177", "17302515", "138664", "19527380", "12745558", "7007454" ]	[ "Folic acid supplements in pregnancy and birth outcome: re-analysis of a large randomised controlled trial and update of Cochrane review.", "Reduction of incidence of prematurity by folic acid supplementation in pregnancy.", "A randomised trial of low dose folic acid to prevent neural tube defects. The Irish Vitamin Study Group.", "Influence of routine administration of folic acid and iron during pregnancy.", "A prophylactic supplementation of iron and folate in pregnancy.", "Double-blind randomised controlled trial of folate treatment before conception to prevent recurrence of neural-tube defects.", "Randomized trial of a physician-based intervention to increase the use of folic acid supplements among women.", "Effect of time of initiation and dose of prenatal iron and folic acid supplementation on iron and folate nutriture of Korean women during pregnancy.", "Multicentric study of efficacy of periconceptional folic acid containing vitamin supplementation in prevention of open neural tube defects from India.", "Impact of micronutrient supplementation during pregnancy on birth weight, duration of gestation, and perinatal mortality in rural western China: double blind cluster randomised controlled trial.", "Effect of N-3 polyunsaturated fatty acid supplementation in pregnancy: the Nuheal trial.", "[Folic acid and pregnancy, a real problem?].", "Iron supplementation studies among pregnant women.", "Pregnancy outcomes in a randomised controlled trial of periconceptional multivitamin supplementation. Final report.", "Folic acid and vitamin B12 supplementation during pregnancy in a population subsisting on a suboptimal diet.", "Folic acid supplement and intrauterine growth.", "EFFECT OF FOLIC ACID AND VITAMIN B12 SUPPLEMENTATION ON TESTS OF FOLATE AND VITAMIN B12 NUTRITION IN PREGNANCY.", "Folate supplements during pregnancy.", "Fortified mineral water improves folate status and decreases plasma homocysteine concentration in pregnant women.", "A prophylactic trial of iron and folic acid supplements in pregnant Burmese women.", "Comparison of effect of daily versus weekly iron supplementation during pregnancy on lipid peroxidation.", "A randomised, double-blind placebo-controlled trial of ascorbic acid supplementation for the prevention of preterm labour.", "Effects of topical and systemic folic acid supplementation on gingivitis in pregnancy." ]	[ "Periconceptual folic acid prevents neural tube defects. The effect of folic acid taken throughout pregnancy is unclear, however. We re-analysed data from a large randomised controlled trial performed between 1966 and 1967 and combined the results with those from trials included in a Cochrane review. A total of 2928 women were randomised: 1977 were allocated to placebo, 466 to folic acid 200 microg/day and 485 to folic acid 5 mg/day. Folic acid supplementation was not associated with any difference in mean birthweight, placental weight or gestational age. When combined with trials in the Cochrane review folic acid at high doses was associated with reduced risk of low birthweight (pooled relative risk 0.73 [95% CI 0.53, 0.99]). We found no conclusive evidence of benefit for folic acid supplementation in pregnant women given from time of booking onwards.", "Folic acid administered to pregnant Bantu, whose diet is low in folate, was associated with a significant reduction in the incidence of prematurity. No such effect could be demonstrated in White patients subsisting on an average Western diet. This suggests that folate deficiency may contribute to the \"pregnancy wastage\" in populations whose dietary folate intake is low, and is a further indication for folic acid supplementation during pregnancy in these groups.", "A randomised trial was initiated in Ireland in 1981 to determine if periconceptional supplementation with either folic acid alone or a multivitamin preparation alone could reduce the recurrence risk of neural tube defects (NTDs) in women with a previously affected pregnancy from 5.0% to 1.0% or less. The trial was concluded before the initial target number of study subjects was reached and without a clear treatment effect being observed. A total of 354 women were randomised to receive one of three treatments: folic acid, multivitamins without folic acid, and folic acid plus multivitamins. At the end of the trial 257 women had had a first trial pregnancy outcome (261 infants/fetuses) where the presence or absence of NTDs was ascertainable. There was one NTD recurrence in the 89 infants/fetuses of women in the multivitamin group and no recurrence in the 172 infants/fetuses of women in the folic acid groups, a non-significant difference. Otherwise eligible women who were pregnant when first contacted constituted a non-randomised control group; there were three recurrences among the 103 infants in this group. The difference in the recurrence rate between the folic acid groups and the non-randomised controls was statistically significant but we have reservations about the validity of this comparison. Although our findings do not provide clear evidence of a protective effect of folic acid supplementation they are consistent with those of the Medical Research Council (MRC) trial which demonstrated the efficacy of folic acid in preventing recurrence of NTDs and they raise the possibility that folic acid may be protective at a much lower dosage than that used in the MRC trial.", "Haematological and folic acid status were assessed in 200 women in the 6th month of pregnancy. Folic acid deficiencies with no or little haematological impairment were found in one third of the cases, and their occurrence increased when the socioeconomic level was low. During the last trimester of pregnancy, the women were given either iron alone or iron and folic acid supplementation. In the mothers, the rise of folate values in serum and red blood cells, in the folic acid-supplemented group, had no obvious haematological consequences, showing that iron therapy alone can, in developed countries, prevent the anaemia in pregnancy. In the infants, there was no difference in the haematological indices, whatever the mothers' treatment had been. However, a significant difference appeared for the gestational age and, therefore, the height and weight. Folic acid supplementation during pregnancy increased its duration by virtually 1 week.", "The supplementation of iron and folic acid were studied in 567 pregnant women with 18 and 26 weeks of gestation. Sixty mg and 180 mg of iron were given daily to pregnant women of group I and group II respectively while 180 mg of iron and 5 mg folic acid were given to group III. The Hb values increased significantly in group II and III after supplementation for 1 1/2 months, however if supplementation was extended for 3 months, highly significant increase in Hb levels were observed in all these groups. These findings indicated that in supplementation for a shorter period, i.e. 1 1/2 months at least 180 mg of iron was needed, and only 60 mg of iron was sufficient to increase Hb levels for a supplementation of 3 months. Vitamin B12 deficiency was not detected in pregnant women both before and after supplementation with iron and iron plus folate for 3 months. It was suggested therefore that perhaps it was not necessary to supplement vitamin B12 to Thai pregnant women. In this study 15% of pregnant women had low serum folate with normal red cell folate level, and a greater number of women with low serum folate concentrations were observed after supplementation with iron alone for 3 months. However, increased serum folate and red cell folate levels after supplementation with 5 mg folic acid indicated that some pregnant women needed folate supplementation in preventing folic acid deficiency during pregnancy.", "A randomized controlled double-blind trial was undertaken in south Wales to prevent the recurrence of neural-tube defects in women who had had one child with a neural-tube defect. Sixty women were allocated before conception to take 4 mg of folic acid a day before and during early pregnancy and 44 complied with these instructions. Fifty-one women were allocated to placebo treatment. There were no recurrences among the compliant mothers but two among the non-compliers and four among the women in the placebo group. Thus there were no recurrences among those who received supplementation and six among those who did not; this difference is significant (p = 0.04). It is concluded that folic acid supplementation might be a cheap, safe, and effective method of primary prevention of neural-tube defects but that this must be confirmed in a large, multicentre trial.", "Fewer than one third of American women take folic acid daily, although many women report that they would take folic acid if their physicians advised them to do so. This study determined the impact of a physician intervention during routine gynecologic visits on folic acid supplementation.\n Patients were assigned randomly to receive brief folic acid counseling, a reminder phone call, and 30 folic acid tablets (n = 162 women; intervention group) or to receive counseling about other preventive health behaviors and a folic acid informational pamphlet (n = 160 women; control group). Self-reported folic acid use was compared at baseline and at 2 months.\n Of the 279 patients who completed the study, weekly folic acid intake increased in the intervention group by 68%, compared with 20% in the control group ( P =.008). No significant differences were found in daily intake. The women who were most influenced by the intervention were black and lower income and not planning pregnancies.\n With little effort expended to encourage folic acid use, gynecologists could potentially reduce the risk of folate-preventable birth defects among their patients by as much as 11%.", "In Korea, it is customary to prescribe iron and folic acid supplements to pregnant women after the 20th wk of gestation; however, little evidence exists to support this practice.\n The objective was to determine the effects of time of initiation and dose of prenatal iron and folic acid supplementation on the iron and folate nutriture of Korean women during pregnancy.\n A total of 131 pregnant women were placed into 1 of 5 experimental groups, either the control group or 1 of 4 supplemented groups. The supplemented groups varied by time of initiation, which was either during the first trimester or at week 20 of gestation, and by dose of iron and folic acid supplements provided, which consisted of either 30 mg Fe plus 175 microg folic acid or 60 mg Fe plus 350 microg folic acid. All supplemented groups continued supplementation until delivery.\n Improvements in iron and folate nutriture were highly dependent on when the supplement program was initiated, but both supplement doses were equally effective. In contrast, the influence of folic acid supplementation on maternal folate status was not as pronounced as was the influence of iron supplementation on iron status.\n In pregnant Korean women, initiating iron and folic acid supplementation earlier during pregnancy may prevent the deterioration of iron and folate nutriture more than does increasing supplement doses in later stages of pregnancy.", "A folic acid containing multivitamin preparation was evaluated for its efficacy in preventing recurrence of open neural tube defect (NTD) in a blind, placebo-controlled randomized trial. The trial was carried out at the five centres in India, viz., Bangalore, Mumbai, Lucknow, New Delhi and Pune.\n The preparation contained 4 mg of folic acid besides calcium, iron, zinc and vitamins A, B1, B2, B6, C, D and nicotinamide. The placebo contained calcium and iron only. A total of 466 women with previous history of giving birth to a child with open NTD were included in the trial (231 in the vitamin group and 235 in the placebo group). The supplementation was given for at least one month prior to conception and up to three months after conception. All women were offered antenatal diagnosis with screening of maternal serum alpha foetoprotein (AFP) and ultrasound.\n Pregnancy outcome with reference to recurrence of NTD was unknown in 137 women in the vitamin group and 142 in the placebo group. The recurrence of open NTD in the vitamin group was 2.92 per cent compared to 7.04 per cent in the placebo group, a reduction by about 60 per cent. The difference, however, was not statistically significant (P = 0.06).\n The study seems to support the role of periconceptional folic acid supplementation in prevention of recurrence of NTDs in the Indian population. The reason for high recurrence rate observed in the placebo group requires further investigation.", "To examine the impact of antenatal supplementation with multiple micronutrients or iron and folic acid compared with folic acid alone on birth weight, duration of gestation, and maternal haemoglobin concentration in the third trimester.\n Cluster randomised double blind controlled trial.\n Two rural counties in north west China.\n 5828 pregnant women and 4697 live births.\n Villages were randomised for all pregnant women to take either daily folic acid (control), iron with folic acid, or multiple micronutrients with a recommended allowance of 15 vitamins and minerals.\n Birth weight, length, and head circumference measured within 72 hours after delivery. Neonatal survival assessed at the six week follow-up visit.\n Birth weight was 42 g (95% confidence interval 7 to 78 g) higher in the multiple micronutrients group compared with the folic acid group. Duration of gestation was 0.23 weeks (0.10 to 0.36 weeks) longer in the iron-folic acid group and 0.19 weeks (0.06 to 0.32 weeks) longer in the multiple micronutrients group. Iron-folic acid was associated with a significantly reduced risk of early preterm delivery (<34 weeks) (relative risk 0.50, 0.27 to 0.94, P=0.031). There was a significant increase in haemoglobin concentration in both iron-folic acid (5.0 g/l, 2.0 to 8.0 g/l, P=0.001) and multiple micronutrients (6.9 g/l, 4.1 to 9.6 g/l, P<0.001) groups compared with folic acid alone. In post hoc analyses there were no significant differences for perinatal mortality, but iron-folic acid was associated with a significantly reduced early neonatal mortality by 54% (relative risk 0.46, 0.21 to 0.98).\n In rural populations in China antenatal supplementation with iron-folic acid was associated with longer gestation and a reduction in early neonatal mortality compared with folic acid. Multiple micronutrients were associated with modestly increased birth weight compared with folic acid, but, despite this weight gain, there was no significant reduction in early neonatal mortality. Pregnant women in developing countries need sufficient doses of iron in nutrient supplements to maximise reductions in neonatal mortality. Trial registration ISRCTN08850194.", "In this placebo controlled, randomised, double blind trial, pregnant women received from the 20th week of gestation onwards either 500 mg docosahexaenoic acid (DHA), 400 mg 5-methyl-tetra-hydro-folate (5-MTHF), or placebo, or a combination of 500 mg DHA and 400 mg 5-MTHF. The dietary supplements were well tolerated; the dropout rates did not differ significantly in the active arms of the study (10% to 19%) from that seen in the placebo group (13%). DHA supplementation resulted in significant enhancement of the contribution of DHA to maternal, placental and venous cord blood lipids.", "The efficacy of prophylactic treatment with ferrous sulfate (80 mg Fe++) and the combination of ferrous sulfate with folic acid (80 mg Fe++ and 350 microgram folic acid) were studied in a double blind trial in the 20th, and again in the 30th and 36th week of pregnancy (29 patients). At the beginning of the treatment (20th week) 29% of the patients showed a pathologically reduced serum folic acid level. Combined therapy has a favorable effect on the folic acid levels in the serum and red blood cells; this was confirmed statistically. At the end of pregnancy, 69% of the patients of the control group (ferrous sulfate) showed a pathologically reduced serum level and 23% a subnormal level in erythrocytes. These results unquestionably justify the prophylactic prescription of folic acid during pregnancy.", "The effect of iron supplementation alone or in combination with ascorbic acid as a preventive and or corrective measure against anemia were tested using pregnant women seeking pre-natal consultation at various health centers in Greater Manila Area. One tablet containing 65 mg iron alone or in combination with ascorbic acid per day during a supplementation period which varied from 16.5 to 17.8 weeks maintained initial hemoglobin and hematocrit levels in non-anemic women. Three tablets of the same iron preparation (total of 195 mg iron) daily resulted in significant increases in hemoglobin and hematocrit in anemic women. Ascorbic acid had no apparent beneficial effect. Considering the positive response to iron treatment, it is recommended that a nationwide program of iron supplementation of pregnant Filipinos be undertaken.", "The effect of periconceptional multivitamin/trace element supplementation on pregnancy outcomes was evaluated in a randomised controlled trial. The final data-base included 5,502 females with confirmed pregnancy. A multivitamin including 0.8 mg folic acid or a trace element were supplemented for at least 28 days before conception and continuing for at least until the second missed menstrual period. Number of pregnancies, terminations of pregnancies, four types of fetal deaths, livebirths including low birth weight, preterm birth and sex ratio were analysed. Periconceptional multivitamin supplementation increased fertility (higher rates of cumulative conceptions and multiple births), had no significant effect on the rate of different groups of fetal deaths, low birth weight and preterm birth in singletons. This primary preventive method can reduce the occurrence and recurrence of neural-tube defects and had no other significant effect on pregnancy outcomes except multiple births.", "nan", "The effect of a folic acid supplment on birth weight and placental weight in women delivering in the early summer in Denmark was investigated. Thirty-six women with normal pregnancy and expected delivery in the first half of June were selected consecutively. They were paired two and two, and allotted to two groups, one of which was supplied daily with 5 mg folic acid, and the second with tablets without folic acid, from the 23rd week of pregnancy. A significant correlation was found between erythrocyte folic acid and birth weight. The infants in the folic acid group were 12.7 per cent heavier than those in the control group (p less than 0.01). A similar difference was found with regard to placental weight and the number of placental cells.", "nan", "In a controlled, prospective trial, the effects of giving ferrous sulphate 50 mg daily to 76 pregnant women was compared with giving ferrous sulphate 50 mg daily plus folic acid 0.5 mg daily to 82 women in 12 general practices in South-east England.No differences in obstetric complications were found between the two groups, although the evidence of some of the listed complications may be too rare for detection in a sample of patients of this size.", "There is no mandatory folic acid fortification of food in Finland. We investigated the effects of mineral water fortified with folic acid, vitamins B6, B12, D and calcium on serum and erythrocyte folate concentrations, serum vitamin B12 and plasma homocysteine concentrations in pregnancy.\n A randomized, controlled, double-blind, parallel-group intervention study.\n Seventy-four pregnant women were recruited from two health care units. The study began at the eleventh week with a two-week run-in period, followed by an eight-week intervention period. The diet was monitored by food records. During the intervention, subjects consumed 1000 mL/day fortified or normal mineral water. The pregnancies were monitored carefully.\n The folate intake was 255 microg/day in the study group and 274 microg/day in the controls. Serum folate concentrations increased in the study group by 10.3 nmol/L and decreased in the controls by 2.7 nmol/L (P<0.05) during the study. The erythrocyte folate concentrations increased in the study group by 360.9 nmol/L and in the controls by 195.6 nmol/L (P=0.004) and serum homocysteine concentrations fell by 1.1 micromol/L and by 0.3 micromol/L, respectively (P<0.05).\n Finnish pregnant women have low dietary folate intake. Fortified mineral water improved folate status and reduced plasma homocysteine concentrations in the pregnant subjects.", "Hemoglobin (Hb) concentration, serum iron level, iron binding capacity and blood folate (Lactobacillus casei) activity were determined in 310 unselected pregnant Burmese women. Hb concentration was less than 11 g/dl in 72% of the women; the serum iron level was less than 50 mug/dl in 33%; serum folate activity was less than 3ng/ml in 13%; and red cell folate activity was less than 100 ng/ml in 17% of the women. Ninety-six of the women in our study were randomly divided into four groups, treated from the 22nd to the 25th week of pregnancy until full term with either ferrous sulfate containing 60 mg elemental iron twice daily, 5 mg folic acid twice daily, a combination of both, or a placebo only. At full term, Hb concentration fell in the groups given placebo or folic acid. On the other hand, in the groups given iron alone or iron plus folic acid there was an increase in Hb of 0.4 and 0.7 g/dl, respectively (intergroup difference not statistically significant). Serum iron and blood folate levels fell in the groups not receiving the appropriate hematinic. In spite of deficient serum and red cell folate levels in 30 and 40%, respectively, of the group on iron alone, the mean Hb concentration increased at full term and none of the women had a Hb concentration lower than 10 g/dl. Blood folate levels were lower in the iron-supplemented group than in the placebo group, indicating that iron deficiency does not aggravate the folate nutritional status.", "To compare the effect of daily versus weekly iron supplementation on lipid peroxidation, hemoglobin levels and maternal and perinatal outcome in non-anemic pregnant women.\n Of 109 women randomly allocated into three groups, 90 completed the study. Group I (n = 30) received daily iron folic acid; Group II (n = 30) received weekly iron folic acid; Group III (n = 30) received daily iron (III)-hydroxide polymaltose complex. Hemoglobin levels, hematological indices, thiobarbituric acid reactive substances (TBARS) and glutathione levels were measured at baseline (14-16 weeks) and at 30-34 weeks. Statistical analysis was done using the anova test.\n Group I had a highly significant increase in TBARS level (0.61 +/- 0.26 micromol/L, P = 0.000) compared to groups II and III in which the change in TBARS was not significant (0.02 +/- 0.06 and 0.007 +/- 0.06 micromol/L, respectively). There was an insignificant fall in glutathione levels in all groups. There was no significant difference in the mean period of gestation, pregnancy complications and neonatal outcome between the three groups. Among 22.2% of women who were non-compliant, Group I had significantly higher incidence of non-compliance (P = 0.016) and side-effects (P = 0.001). Final hemoglobin was higher in Group I than II (11.9 +/- 1.2, 11.3 +/- 0.9, respectively, P = 0.041). The TBARS level was not statistically different between preterm and term deliveries. Nine out of 11 patients who developed hypertension during pregnancy had preeclampsia. The final TBARS level was significantly higher in these women (P = 0.000).\n Daily supplementation with ferrous sulphate results in greater lipid peroxidation than weekly supplementation, the latter is comparable with daily iron (III)-hydroxide polymaltose complex. Lipid peroxidation levels are significantly higher in preeclampsia.", "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.", "A double-blind study evaluated the effects of systemic and topical folate on gingival inflammation during the fourth and eighth months of pregnancy. Thirty women were randomly divided into three groups. Group A received placebo mouthwash and tablets; Group B; placebo mouthwash and 5 mg folate tablets; Group C: folate mouthwash and placebo tablets. Supplementation lasted for 14 days during months 4 and 8. Subjects took one tablet daily and rinsed twice daily for 1 min with the mouthwash. At the start and finish of each 14-day period, fasting serum and red cell folate levels were estimated and oral status assessed by a plaque index (P1I), a gingival index (GI), and gingival exudate flow meter (GEF). Subjects completed 1-week diet sheets which were analysed for dietary folate. All groups were similar in each parameter at the start. Correlation was demonstrated between GI and P1I, and between GI and GEF. GI tended to increase throughout pregnancy in all groups except Group C, when in the eighth month there was a highly significant improvement (0.001 less than P 0.01) despite no significant change in P1I. Although dietary intake of folate was significantly higher during the eighth month in Group C as compared with Groups A and B, (0.001 less than P less than 0.01), the folate mouthwash produced highly significantly improvement in gingival health in pregnancy." ]	We found no conclusive evidence of benefit of folic acid supplementation during pregnancy on pregnancy outcomes.
CD000009	[ "9818805", "10024707", "7183202", "10689659", "17359519", "6942317", "17698433", "12356614", "19885943", "11239191", "16259308", "9209728", "11528199", "9085389", "1439060", "11495172", "15344424" ]	[ "Randomized trial of acupuncture for nicotine withdrawal symptoms.", "A single-blind, placebo-controlled trial of a simple acupuncture treatment in the cessation of smoking.", "Acupuncture therapy for the treatment of tobacco smoking addiction.", "Electrical stimulation therapy in the treatment of cigarette smoking.", "Acupressure for smoking cessation--a pilot study.", "The efficacy of acupuncture as an aid to stopping smoking.", "A randomized controlled clinical trial of auricular acupuncture in smoking cessation.", "Auricular acupuncture, education, and smoking cessation: a randomized, sham-controlled trial.", "A six-week acupoint stimulation intervention for quitting smoking.", "Acupuncture and transcutaneous nerve stimulation in stroke rehabilitation: a randomized, controlled trial.", "Laser acupuncture for mild to moderate depression in a primary care setting--a randomised controlled trial.", "Evaluation of cranial electrostimulation therapy on short-term smoking cessation.", "Prospective randomized trial using laser acupuncture versus desmopressin in the treatment of nocturnal enuresis.", "Effects of acupuncture on smoking cessation or reduction for motivated smokers.", "A randomised 2 x 2 factorial design to evaluate different smoking cessation methods.", "Strike while the iron is hot: can stepped-care treatments resurrect relapsing smokers?", "Acupressure and Transcutaneous Electrical Acupoint Stimulation in improving fatigue, sleep quality and depression in hemodialysis patients." ]	[ "Acupuncture is frequently used for smoking cessation. Positive results from uncontrolled studies have not been supported by meta-analysis of controlled trials. One possible reason for this is that the optimal acupuncture technique was not applied or that the technique was not repeated sufficiently often.\n A randomized, sham-controlled trial was performed with 2 parallel treatment arms; the participant and the evaluator were unaware of which treatment was received. Seventy-six adults who wanted to stop smoking received either 100-Hz electroacupuncture with needles inserted into the appropriate point in each ear or a sham control procedure over the mastoid bone. Interventions were given on days 1, 3, and 7 of smoking cessation. Nicotine withdrawal symptoms were measured by visual analog scale scores recorded in a daily diary for 14 days; smoking cessation was confirmed objectively.\n There was no significant difference between the mean reduction of withdrawal symptom scores of the 2 groups from day 1 to day 14. Fifteen participants (39%) who received electroacupuncture and 16 participants (42%) who received a sham procedure were abstinent on day 14.\n This form of electroacupuncture is no more effective than placebo in reducing nicotine withdrawal symptoms.", "Tobacco smoking is a major cause of preventable disease and premature death. Physicians should play an active role in the control of smoking by encouraging cessation and helping the smoker to choose the most suitable aid to cessation.\n To evaluate a simple, ear acupuncture treatment for the cessation of smoking.\n Randomized, single-blind, placebo-controlled trial of 78 currently smoking volunteers from the general public. Volunteers attended an acupuncture clinic in a general practice setting and were given a single treatment of electroacupuncture using two needles at either an active or a placebo site plus self-retained ear seeds for two weeks. The major outcome measure was biochemically validated total cessation of smoking at six months.\n A total of 12.5% of the active treatment group compared with 0% of the placebo group ceased smoking at six months (P = 0.055, 95% confidence interval -0.033 to 0.323).\n This simple ear electroacupuncture treatment was significantly more effective in helping volunteers to quit smoking than placebo treatment.", "Acupuncture has been reported as an effective treatment for some addictions. The purpose of this study was to evaluate acupuncture treatment effect on the cigarette smoking habit with a motivated population in a controlled clinical setting. From a volunteer research population, sixteen matched pairs were assembled according to age, sex, and severity of smoking habit. Research subjects were randomly assigned to real or sham acupuncture treatment groups. Self-reported cigarette logs were measured pre-treatment and post-treatment. Analysis of variants confirmed homogeneity of group pre-treatment cigarette consumption. Cigarette consumption significantly decreased in both th e real and sham treatment groups. Treatment group, age, sex, or severity of smoking habit were not significant factors in treatment effects for cessation of smoking. Legitimate crossover treatment for sham research group showed a significant decrease (p less than or equal to 0.05) in cigarette consumption; this change was not statistically different from change in cigarette consumption during placebo treatment. A discussion of acupuncture point selection rationale is made as is an analysis of Tehchi sensations and subjective reports of appetite for cigarettes. Acupuncture did not enhance the cessation of cigarette smoking in this study.", "In this study electrical stimulation therapy (EST) is explored as a possible new treatment for smoking cessation within a randomized controlled trial. The investigation follows reports of several authors that electrical stimulation applied to specific acupuncture points is effective in treating a variety of drug dependencies, including cigarette smoking. Three key features of treatment (electrical stimulation, frequency modulation, and electrode placement), were investigated in a 2 x 2 x 2 factorial design, resulting in eight treatment combinations. Out of 265 smokers recruited into the trial 216 completed the one-week treatment. Outcome was assessed in terms of complete abstinence from smoking and symptomatic relief of withdrawal symptoms. Smokers receiving active electrical stimulation obtained higher abstinence rates than those in the inactive groups although the difference did not achieve statistical significance (all active vs. all placebo groups: lambda 1,1(2) = 0.50, p > 0.10, 95% confidence interval = -8.04 to +17.44%; most effective vs. least effective group: lambda 1,1(2) = 3.11, p = 0.08, CI0.95 = -2.2 to +48.8%). The efficacy of electrical stimulation therapy for smoking is not supported.", "Tobacco smoking is a serious risk to health: several therapies are available to assist those who wish to stop. Smokers who approach publicly funded stop-smoking clinics in the UK are currently offered nicotine replacement therapy (NRT) or bupropion, and group behaviour therapy, for which there is evidence of effectiveness. Acupuncture and acupressure are also used to help smokers, though a systematic review of the evidence of their effectiveness was inconclusive. The aim of this pilot project was to determine the feasibility of a study to test acupressure as an adjunct to one anti-smoking treatment currently offered, and to inform the design of the study.\n An open randomised controlled pilot study was conducted within the six week group programme offered by the Smoking Advice Service in Plymouth, UK. All participants received the usual treatment with NRT and group behavioural therapy, and were randomised into three groups: group A with two auricular acupressure beads, group B with one bead, and group C with no additional therapy. Participants were taught to press the beads when they experienced cravings. Beads were worn in one ear for four weeks, being replaced as necessary. The main outcome measures assessed in the pilot were success at quitting (expired CO < or = 9 ppm), the dose of NRT used, and the rating of withdrawal symptoms using the Mood and Symptoms Scale.\n From 49 smokers attending four clinics, 24 volunteered to participate, 19 attended at least once after quitting, and seven remained to the final week. Participants who dropped out reported significantly fewer previous quit attempts, but no other significant differences. Participants reported stimulating the beads as expected during the initial days after quitting, but most soon reduced the frequency of stimulation. The discomfort caused by the beads was minor, and there were no significant side effects. There were technical problems with adhesiveness of the dressing. Reporting of NRT consumption was poor, with much missing data, but reporting of ratings of withdrawal symptom scores was nearly complete. However, these showed no significant changes or differences between groups for any week.\n Any effects of acupressure on smoking withdrawal, as an adjunct to the use of NRT and behavioural intervention, are unlikely to be detectable by the methods used here and further preliminary studies are required before the hypothesis can be tested.", "The present study examines the usefulness of acupuncture as an aid to stopping smoking. Results from 405 subjects show acupuncture can help between 5 and 15 percent of the population to stop smoking for at least six months. Using chronically implanted press needles, previously reported 'effective' auricular acupuncture points for smoking cessation are shown to be no better than 'placebo' auricular points. Additional electroacupuncture on the hand neither increases the probability of stopping smoking nor enhances the reduction in smoking at three week, three month or six month follow-up periods. It is therefore likely that a large psychological component is attached to acupuncture to stop people smoking.", "Tobacco smoking is responsible for human diseases of the lung, heart, circulatory system and various kinds of cancers, and is a serious public health problem worldwide. Acupuncture has been promoted as a treatment modality for smoking cessation. However, its efficacy still remains controversial.\n We conducted a prospective, randomized, controlled trial using auricular acupuncture for smoking cessation in 131 adults who wanted to stop smoking. Thirteen subjects withdrew from the study and 118 subjects were included in the final analyses (mean age, 53.7 +/- 16.8 years; 100 males, 18 females). The treatment group (n = 59) received auricular acupuncture in Shen Men, Sympathetic, Mouth and Lung points for 8 weeks. The control group (n = 59) received sham acupuncture in non-smoking-cessation-related auricular acupoints (Knee, Elbow, Shoulder and Eye points). The enrolled subjects were then followed monthly for 6 months after stopping the acupuncture treatment.\n Between both groups before acupuncture treatment, there was no significant difference with regard to gender, mean age, education level, and mean values for the age at which smoking started, smoking duration, daily number of cigarettes smoked and nicotine dependent score. At the end of treatment, cigarette consumption had significantly decreased in both groups, but only the treatment group showed a significant decrease in the nicotine withdrawal symptom score. Smoking cessation rate showed no significant difference between the treatment group (27.1%) and the control group (20.3%) at the end of treatment. There was also no significant difference in the smoking cessation rate between the treatment group (16.6%) and the control group (12.1%) at the end of follow-up. There were no major side effects of auricular acupuncture in both groups.\n Our results showed that auricular acupuncture did not have a better efficacy in smoking cessation compared to sham acupuncture. Combined acupuncture with behavior counseling or with nicotine replacement therapy should be used in further smoking cessation trials to enhance the success rate of smoking cessation.", "This study examined the effect of acupuncture alone and in combination with education on smoking cessation and cigarette consumption.\n We prospectively studied 141 adults in a quasi-factorial design using acupuncture, sham acupuncture, and education.\n All groups showed significant reductions in smoking and posttreatment cigarette consumption, with the combined acupuncture-education group showing the greatest effect from treatment. The trend continued in follow-up; however, significant differences were not maintained. Greater pack-year history (i.e. the number of years smoking multiplied by baseline number of cigarettes smoked per year, divided by 20 cigarettes per pack) negatively correlated with treatment effect. Trend analysis suggested 20 pack-years as the cutoff point for this correlation.\n Acupuncture and education, alone and in combination, significantly reduce smoking; however, combined they show a significantly greater effect, as seen in subjects with a greater pack-year history.", "This study creates a six-week acupoint stimulation program for quitting smoking by conducting an experimental research design and then evaluating its effects. A total of 59 smokers, 28 +/- 7.6 years of mean age, volunteered to participate and were randomly assigned to the experimental or sham group. The current investigation administered anti-smoking acupoints to the experimental group for six weeks, whereas the sham group used sham acupoints for six weeks. Before and after the six-week intervention, the participants completed questionnaires and offered blood samples. This research collected data of demographic factors, serum cotinine, carbon monoxide exhalation, daily tobacco consumption, and quit smoking rate of participants before and after the six-week intervention. After the intervention, it showed no significant differences in the serum level of cotinine and carbon monoxide exhalation between the two groups. The quit rate in the experimental group was 13.3% and 13.7% in the sham group. However, daily tobacco consumption was 10 cigarettes in the experimental group and 11.21 cigarettes in the sham group. This experimental study used the sham group as the control, resulting in no statistically significant findings. Future studies need more evidence-based research on the exact effect or placebo effect of acupoint stimulation and the appropriate design for sham acupoint, to examine quitting effect using acupoint stimulation in adult smokers.", "In small trials with control groups that receive no intervention, acupuncture has been reported to improve functional outcome after stroke. We studied effects of acupuncture and transcutaneous electrical nerve stimulation on functional outcome and quality of life after stroke versus a control group that received subliminal electrostimulation.\n In a multicenter randomized controlled trial involving 7 university and district hospitals in Sweden, 150 patients with moderate or severe functional impairment were included. At days 5 to 10 after acute stroke, patients were randomized to 1 of 3 intervention groups: (a) acupuncture, including electroacupuncture; (b) sensory stimulation with high-intensity, low-frequency transcutaneous electrical nerve stimulation that induces muscle contractions; and (c) low-intensity (subliminal) high-frequency electrostimulation (control group). A total of 20 treatment sessions were performed over a 10-week period. Outcome variables included motor function, activities of daily living function, walking ability, social activities, and life satisfaction at 3-month and 1-year follow-up.\n At baseline, patients in each group were closely similar in all important prognostic variables. At 3-month and 1-year follow-ups, no clinically important or statistically significant differences were observed between groups for any of the outcome variables. The 3 treatment modalities were all conducted without major adverse effects.\n When compared with a control group that received subliminal electrostimulation, treatment during the subacute phase of stroke with acupuncture or transcutaneous electrical nerve stimulation with muscle contractions had no beneficial effects on functional outcome or life satisfaction.", "Depression is a major public health problem. There is some evidence supporting the effectiveness of needle acupuncture in its treatment. Laser stimulation, regarded here as a modality of acupuncture, is non-invasive and therefore free of infection risk; and it is acceptable to patients with needle phobia. The technique is relatively easily learned by community-based general practitioners. It is also amenable to sham control and therefore double-blinding in clinical trials. A double-blind randomised controlled trial was conducted to test the efficacy of low level laser acupuncture in mild to moderate depression.\n Thirty patients with depression were randomised to receive either active or inactive laser treatment. The laser unit could be switched to one of two settings. One switch position delivered active laser acupuncture and the other was inactive (sham). In the active mode, 0.5J was delivered to each of six to eight individually tailored acupuncture sites per visit. All patients were treated twice weekly for four weeks then weekly for a further four weeks. The patients and the acupuncturist were both blinded to conditions. Outcome was assessed using the Beck Depression Inventory at baseline, weeks four and eight during treatment, and at 4 and 12 weeks following the treatment.\n At the end of the treatment period, Beck Depression Inventory scores fell from baseline by 16.1 points in the intervention group and by 6.8 points in the sham control group (P<0.001). The difference showed only a trend four weeks later, but was again significant after 12 weeks (P=0.007). Laser acupuncture was well tolerated with transient fatigue as the most common adverse effect.\n Laser acupuncture may be worth further investigation as a treatment for mild to moderate depression in primary care.", "The effects of cranial electrical stimulation (CES) on short-term smoking cessation were evaluated in a double-blind study of cigarette smokers who wished to stop smoking. Subjects were randomly assigned to a CES- (n = 51) or a sham-treated group (n = 50). On 5 consecutive days subjects received CES treatments (30-microA, 2-msec, 10-Hz pulsed signal) or no electrical current (sham). There were no significant differences between groups on daily cigarettes smoked, exhaled carbon monoxide, urinary cotinine levels, treatment retention, smoking urges, or total tobacco withdrawal scores, although subjects in the CES group had less cigarette craving and anxiety during the first 2 experimental days. The ineffectiveness of CES to reduce withdrawal symptoms and facilitate smoking cessation are similar to results of other clinical studies of CES in drug dependence, although positive effects of CES in animal studies have been reported.", "Several treatment modalities for children suffering from monosymptomatic nocturnal enuresis are available, but desmopressin is a well-established option. On the other hand, alternative nonpharmacological therapies such as laser acupuncture are more frequently requested by the parents. To our knowledge, there is no prospective randomized trial which evaluated the efficacy of such an alternative approach in comparison with the widespread use of desmopressin.\n Forty children aged over 5 years presenting with primary nocturnal enuresis underwent a previous evaluation of their voiding function to assure normal voiding patterns and a high nighttime urine production. Then the children were randomized into two groups: group A children were treated with desmopressin alone, and group B children underwent laser acupuncture. All children were investigated after a minimum follow-up period of 6 month to evaluate the duration of the response.\n The children of both groups had an initial mean frequency of 5.5 wet nights per week. After a minimum follow-up period of 6 months reevaluation revealed a complete success rate of 75% in the desmopressin-treated group. Additional 10% of the children had a reduction of their wet nights of more than 50%. On the other hand, 6 months after laser acupuncture, 65% of the randomized children were completely dry. Another 10% had a reduction of the enuresis frequency of more than 50% per week. 20% of the children in the desmopressin-treated group did not respond at all as compared with 15% in the acupuncture-treated group. Statistical evaluation revealed no significant differences among the response rates in both groups.\n Im comparison with pharmacological therapy using desmopressin, our study shows that laser acupuncture should be taken into account as an alternative, noninvasive, painless, cost-effective, and short-term therapy for children with primary nocturnal enuresis in case of a normal bladder function and high nighttime urine production. Success rates indicated no statistically significant differences between the well-established desmopressin therapy and the alternative laser acupuncture.", "This study was undertaken to examine the effects of acupuncture on smoking reduction and possibly also cessation and to examine whether some acupoints are more effective than others for smoking cessation.\n A total of 46 healthy men and women, 39 +/- 9 years of age (mean +/- SD), who smoked 20 +/- 6 cigarettes per day and had smoked for 23 +/- 8 years, and who wanted to quit smoking, volunteered to participate. The subjects were randomly assigned to two groups. One group was given acupuncture treatment at points previously used for anti-smoking (test group, TG). The other group was given acupuncture treatment at points assumed to have no effect for smoking cessation (control group, CG). Before each treatment and after the last treatment each subject answered questionnaires about his or her smoking habits and attitudes. In addition the concentrations of serum cotinine, serum thiocyanate, serum peroxides, and plasma fibrinogen were measured before the first and after the last acupuncture treatment.\n The daily cigarette consumption fell during the treatment period in both groups, but the reduction was larger for TG than for CG (P < 0.002). Altogether 31% of subjects in TG had quit smoking completely at the end of the treatment, compared with none in CG. For TG the concentrations of cotinine and thiocyanate were reduced significantly after the treatment period (P < 0.001), but no significant reductions were observed for CG. For both groups the taste of tobacco worsened during the treatment period, but the effect was more pronounced for TG than for CG (P < 0.05). The desire to smoke fell significantly in both groups after treatment, and the reduction was larger for TG than for CG (P < 0.001). No significant changes in serum peroxides and plasma fibrinogen concentrations were observed during the treatment period for either group.\n This study suggests that acupuncture may help motivated smokers to reduce their smoking or even quit smoking completely. Different acupoints appear to have different effects for smoking cessation and reduction.", "A study with a 2 x 2 factorial design was performed to evaluate the effectiveness of acupuncture, of nicotine gum and the effect of the association on smoking cessation. After a one-year follow-up period, the success rates were in the same order of magnitude for nicotine gum (active treatment: 10%, placebo: 8%) group and for acupuncture (active treatment: 8%, placebo: 10%) group.", "The efficacies of 2 group counseling step-up treatments for smoking cessation, cognitive-behavioral/skill training therapy (CBT) and motivational interviewing/supportive (MIS) therapy, were compared with brief intervention (BI) treatment in a sample of 677 smokers. Differential efficacy of the 2 step-up treatments was also tested in smokers at low and high risk for relapse (no smoking vs. any smoking during the first postquit week. respectively). All participants received 8 weeks of nicotine patch therapy. BI consisted of 3 brief individual cessation counseling sessions; CBT and MIS participants received BI treatment and 6 group counseling sessions. Neither CBT nor MIS treatment improved long-term abstinence rates relative to BI. Limited support was found for the hypothesis that high-risk smokers would benefit more from MIS than CBT. Other hypotheses were not supported.", "The purpose of this study was to test the effectiveness of acupressure and Transcutaneous Electrical Acupoint Stimulation (TEAS) on fatigue, sleep quality and depression in patients who were receiving routine hemodialysis treatment. The study was a randomized controlled trial; qualified patients were randomly assigned to acupressure, TEAS or control groups. Patients in the acupressure and TEAS groups received 15 minutes of treatment 3 times a week for 1 month, whereas patients in the control group only received routine unit care. A total of 106 patients participated in the study. Methods of measurement included the revised Piper Fatigue Scale (PFS), the Pittsburgh Sleep Quality Index and the Beck Depression Inventory. Data were collected at baseline, during the intervention and post-treatment. The results indicated that patients in the acupressure and TEAS groups had significantly lower levels of fatigue, a better sleep quality and less depressed moods compared with patients in the control group based upon the adjusted baseline differences. However, there were no differences between acupressure and TEAS groups in outcome measures. This study provides an alternative method for health care providers in managing dialysis patients with symptoms of fatigue, poor sleep or depression." ]	There is no consistent, bias-free evidence that acupuncture, acupressure, laser therapy or electrostimulation are effective for smoking cessation, but lack of evidence and methodological problems mean that no firm conclusions can be drawn. Further, well designed research into acupuncture, acupressure and laser stimulation is justified since these are popular interventions and safe when correctly applied, though these interventions alone are likely to be less effective than evidence-based interventions.
CD005563	[ "16181163", "11784964", "11380742", "16137275", "16319303", "2913977" ]	[ "Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized placebo-controlled study.", "[Use of procholinergics in the prevention of postoperative delirium in hip fracture surgery in the elderly. A randomized controlled trial].", "Reducing delirium after hip fracture: a randomized trial.", "Efficacy of a comprehensive geriatric intervention in older patients hospitalized for hip fracture: a randomized, controlled trial.", "Donepezil in the prevention and treatment of post-surgical delirium.", "Prevention of thromboembolism in hip-fracture patients. Comparison of low-dose heparin and low-molecular-weight heparin combined with dihydroergotamine." ]	[ "To study the effectiveness of haloperidol prophylaxis on incidence, severity, and duration of postoperative delirium in elderly hip-surgery patients at risk for delirium.\n Randomized, double-blind, placebo-controlled trial.\n Large medical school-affiliated general hospital in Alkmaar, The Netherlands.\n A total of 430 hip-surgery patients aged 70 and older at risk for postoperative delirium.\n Haloperidol 1.5 mg/d or placebo was started preoperatively and continued for up to 3 days postoperatively. Proactive geriatric consultation was provided for all randomized patients.\n The primary outcome was the incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and Confusion Assessment Method criteria). Secondary outcomes were the severity of delirium (Delirium Rating Scale, revised version-98 (DRS-R-98)), the duration of delirium, and the length of hospital stay.\n The overall incidence of postoperative delirium was 15.8%. The percentage of patients with postoperative delirium in the haloperidol and placebo treatment condition was 15.1% and 16.5%, respectively (relative risk=0.91, 95% confidence interval (CI)=0.6-1.3); the mean highest DRS-R-98 score+/-standard deviation was 14.4+/-3.4 and 18.4+/-4.3, respectively (mean difference 4.0, 95% CI=2.0-5.8; P<.001); delirium duration was 5.4 versus 11.8 days, respectively (mean difference 6.4 days, 95% CI=4.0-8.0; P<.001); and the mean number of days in the hospital was 17.1+/-11.1 and 22.6+/-16.7, respectively (mean difference 5.5 days, 95% CI=1.4-2.3; P<.001). No haloperidol-related side effects were noted.\n Low-dose haloperidol prophylactic treatment demonstrated no efficacy in reducing the incidence of postoperative delirium. It did have a positive effect on the severity and duration of delirium. Moreover, haloperidol reduced the number of days patients stayed in the hospital, and the therapy was well tolerated.", "40 to 50% of elderly with hip fracture present delirium. The morbimortality increase in patients whose presented delirium.\n To study the use of citicoline (CDP choline) in the prevention of delirium in elderly under hip fracture surgery.\n A randomized control trial. The patients with hip fracture without dementia or an other organic brain illness. The medication were administered 24 hours before and during 4 days after surgery. The doses was 1.2 g/day. The primary outcome measure was percentage of patients with delirium measured with Abbreviated Mental Test (AMT) and Confusion Assessment Method (CAM). The Mini Mental State (MMS) was used before and 4 days after surgery. All treatment comparation was considered statistically significant at p< 0.05 calculating chi square and Wilcoxon test.\n The sample size was 81 patients (46 placebo and 35 citicoline). The mean age was 79.45 for tested group and 79.97 for placebo. There was no statistically significant difference between groups with respect to ASA class of anesthesia. The incidence of delirium was 17.39% in placebo and 11.76% in citicoline group (p= 0.6). CAM and AMT at 1, 2, 3, 4 days post surgery was not significant in placebo and citicoline group (p= 0.8 and p= 0.34).\n In the present study the citicoline did not prevent or reduce the incidence of delirium in hip fracture surgery in elderly.", "Delirium (or acute confusional state) affects 35% to 65% of patients after hip-fracture repair, and has been independently associated with poor functional recovery. We performed a randomized trial in an orthopedic surgery service at an academic hospital to determine whether proactive geriatrics consultation can reduce delirium after hip fracture.\n Prospective, randomized, blinded.\n Inpatient academic tertiary medical center.\n 126 consenting patients 65 and older (mean age 79 +/- 8 years, 79% women) admitted emergently for surgical repair of hip fracture.\n Detailed assessment through interviews with patients and designated proxies and review of medical records was performed at enrollment to ascertain prefracture status. Subjects were then randomized to proactive geriatrics consultation, which began preoperatively or within 24 hours of surgery, or \"usual care.\" A geriatrician made daily visits for the duration of the hospitalization and made targeted recommendations based on a structured protocol. To ascertain study outcomes, all subjects underwent daily, blinded interviews for the duration of their hospitalization, including the Mini-Mental State Examination (MMSE), the Delirium Symptom Interview (DSI), and the Memorial Delirium Assessment Scale (MDAS). Delirium was diagnosed using the Confusion Assessment Method (CAM) algorithm.\n The 62 patients randomized to geriatrics consultation were not significantly different (P>.1) from the 64 usual-care patients in terms of age, gender, prefracture dementia, comorbidity, type of hip fracture, or type of surgical repair. Sixty-one percent of geriatrics consultation patients were seen preoperatively and all were seen within 24 hours postoperatively. A mean of 10 recommendations were made throughout the duration of the hospitalization, with 77% adherence by the orthopedics team. Delirium occurred in 20 /62 (32%) intervention patients, versus 32 / 64 (50%) usual-care patients (P =.04), representing a relative risk of 0.64 (95% confidence interval (CI) = 0.37-0.98) for the consultation group. One case of delirium was prevented for every 5.6 patients in the geriatrics consultation group. There was an even greater reduction in cases of severe delirium, occurring in 7/ 60 (12%) of intervention patients and 18 / 62 (29%) of usual-care patients, with a relative risk of 0.40 (95% CI = 0.18-0.89). Despite this reduction in delirium, length of stay did not significantly differ between intervention and usual-care groups (median +/- interquartile range = 5 +/- 2 days in both groups), likely because protocols and pathways predetermined length of stay. In subgroup analyses, geriatrics consultation was most effective in reducing delirium in patients without prefracture dementia or activities of daily living (ADL) functional impairment.\n Proactive geriatrics consultation was successfully implemented with good adherence after hip-fracture repair. Geriatrics consultation reduced delirium by over one-third, and reduced severe delirium by over one-half. Our trial provides strong preliminary evidence that proactive geriatrics consultation may play an important role in the acute hospital management of hip-fracture patients.", "To evaluate whether an early multidisciplinary geriatric intervention in elderly patients with hip fracture reduced length of stay, morbidity, and mortality and improved functional evolution.\n Randomized, controlled intervention trial.\n Orthopedic ward in a university hospital.\n Three hundred nineteen patients aged 65 and older hospitalized for hip fracture surgery.\n Participants were randomly assigned to a daily multidisciplinary geriatric intervention (n=155) or usual care (n=164) during hospitalization in the acute phase of hip fracture.\n Primary endpoints were in-hospital length of stay and incidence of death or major medical complications. Secondary endpoints were the rate of recovery of previous activities of daily living and ambulation ability at 3, 6, and 12 months.\n Median length of stay was 16 days in the geriatric intervention group and 18 days in the usual care group (P=.06). Patients assigned to the geriatric intervention showed a lower in-hospital mortality (0.6% vs 5.8%, P=.03) and major medical complications rate (45.2% vs 61.7%, P=.003). After adjustment for confounding variables, geriatric intervention was associated with a 45% lower probability of death or major complications (95% confidence interval=7-68%). More patients in the geriatric intervention group achieved a partial recovery at 3 months (57% vs 44%, P=.03), but there were no differences between the groups at 6 and 12 months.\n Early multidisciplinary daily geriatric care reduces in-hospital mortality and medical complications in elderly patients with hip fracture, but there is not a significant effect on length of hospital stay or long-term functional recovery.", "Delirium is a frequent complication of major surgery in older persons. The authors evaluated the possible benefit of donepezil versus placebo in the prevention and treatment of postoperative delirium in an older population without dementia undergoing elective total joint-replacement surgery.\n A sample of 80 patients participated in this randomized, double-blind, placebo-controlled trial of donepezil. Each participant was evaluated before surgery and then received donepezil or placebo for 14 days before surgery and 14 days afterward. Postoperative delirium was assessed with the Delirium Symptom Interview, Confusion Assessment Method, daily medical record, nurse-observation reviews, and DSM-IV diagnostic criteria for delirium. Subsyndromal delirium was also assessed for each participant.\n Delirium, diagnosed by DSM-IV criteria, was found on at least 1 postoperative day in 18.8% of subjects, but there were no significant differences between the donepezil and placebo groups. When delirium was present, it lasted only 1 day, and there was no difference between the groups. Subsyndromal delirium was found on at least 1 postoperative day for 68.8% of subjects, and, when this occurred, lasted 2 days or less, on average. There was no difference between the groups in the occurrence or duration of subsyndromal delirium. There was no difference between the groups in disposition to home or to another facility.\n This pilot study was unable to demonstrate a benefit for donepezil in preventing or treating delirium in a relatively young and cognitively-intact group of elderly patients undergoing elective orthopedic surgery. Furthermore, postoperative delirium was not a major problem in this population.", "In a prospective, double-blind, controlled study, we compared the antithrombotic efficacy of low-dose heparin with dihydroergotamine (A), low-molecular-weight heparin with dihydroergotamine (B), and placebo (C). Two hundred and thirteen patients surgically treated for fractures of the hip were randomly divided into three groups. One hundred and sixty-one patients were analyzed. All thrombi were verified by ascending phlebography. Nine patients died within 1 month after operation. A and B proved to be equally safe but failed to provide any protection against deep-vein thrombosis, although B showed a tendency to reduce the incidence. Mortality within 1 month of operation was unaffected by the type of prophylaxis." ]	Research evidence on effectiveness of interventions to prevent delirium is sparse. Based on a single study, a programme of proactive geriatric consultation may reduce delirium incidence and severity in patients undergoing surgery for hip fracture. Prophylactic low dose haloperidol may reduce severity and duration of delirium episodes and shorten length of hospital admission in hip surgery. Further studies of delirium prevention are needed.
CD001090	[ "10745332", "18074471", "10832472", "15803051", "1517923", "2585237", "2194270", "12884156", "7996367", "16540956", "3195529", "9339113", "9722035", "17623736", "10917292", "1865542", "8797612", "9221964", "8160279", "8641639", "11134431", "10074720", "21962214", "9609411", "11320043", "8429321", "10103305", "8607936", "12225613", "8079448", "8489107", "11342473", "1901083", "12632426", "16220082" ]	[ "Multicenter randomized placebo controlled trial of therapy with intravenous immunoglobulin in decreasing mortality due to neonatal sepsis.", "Score-based immunoglobulin G therapy of patients with sepsis: the SBITS study.", "Intravenous immunoglobulin for prophylaxis of nosocomial sepsis.", "Effects of high-dose of intravenous immunoglobulin and antibiotics on survival for severe sepsis undergoing surgery.", "Intravenous immune globulin therapy for early-onset sepsis in premature neonates.", "Use of intravenously administered immune globulin to prevent nosocomial sepsis in low birth weight infants: report of a pilot study.", "Intravenous gammaglobulin in the prophylaxis of late sepsis in very-low-birth-weight infants: preliminary results of a randomized, double-blind, placebo-controlled trial.", "Intravenous immunoglobulin G therapy in streptococcal toxic shock syndrome: a European randomized, double-blind, placebo-controlled trial.", "Intravenous immune globulin prophylaxis of late-onset sepsis in premature neonates.", "IgMA-enriched immunoglobulin in neutropenic patients with sepsis syndrome and septic shock: a randomized, controlled, multiple-center trial.", "IgM-enriched intravenous immunoglobulin therapy in neonatal sepsis.", "Intravenous immunoglobulin for sepsis prevention in preterm infants.", "Antithrombin III in patients with severe sepsis. A randomized, placebo-controlled, double-blind multicenter trial plus a meta-analysis on all randomized, placebo-controlled, double-blind trials with antithrombin III in severe sepsis.", "Intravenous immunoglobulin in primary and secondary chronic progressive multiple sclerosis: a randomized placebo controlled multicentre study.", "A randomized trial comparing peripherally inserted central venous catheters and peripheral intravenous catheters in infants with very low birth weight.", "A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. The XOMA Sepsis Study Group.", "INTERSEPT: an international, multicenter, placebo-controlled trial of monoclonal antibody to human tumor necrosis factor-alpha in patients with sepsis. International Sepsis Trial Study Group.", "A randomised clinical trial comparing interferon-alpha and intravenous immunoglobulin in polyneuropathy associated with monoclonal IgM. The IgM-associated Polyneuropathy Study Group.", "The use of IgM-enriched intravenous immunoglobulin for the treatment of neonatal sepsis in preterm infants.", "Prophylaxis against infections with low-dose intravenous immunoglobulins (IVIG) in chronic lymphocytic leukemia. Results of a crossover study.", "A randomized trial of granulocyte-macrophage colony-stimulating factor in neonates with sepsis and neutropenia.", "The use of prophylactic intravenous immunoglobulin therapy in very low birthweight infants.", "Treatment of neonatal sepsis with intravenous immune globulin.", "Antithrombin III (ATIII) replacement therapy in patients with sepsis and/or postsurgical complications: a controlled double-blind, randomized, multicenter study.", "A trial of recombinant human granulocyte colony stimulating factor for the treatment of very low birthweight infants with presumed sepsis and neutropenia.", "Intravenous immunoglobulin treatment in patients with chronic inflammatory demyelinating polyneuropathy: a double blind, placebo controlled study.", "A randomized, controlled trial of prophylactic granulocyte-macrophage colony-stimulating factor in human newborns less than 32 weeks gestation.", "Intravenous immunoglobulin for treatment of recurrent pregnancy loss.", "The effects of IgM-enriched immunoglobulin preparations in patients with severe sepsis [ISRCTN28863830].", "No beneficial effect of low-dose fetal intravenous gammaglobulin administration in combination with intravascular transfusions in severe Rh D haemolytic disease.", "High-dose weekly intravenous immunoglobulin to prevent infections in patients undergoing autologous bone marrow transplantation or severe myelosuppressive therapy. A study of the American Bone Marrow Transplant Group.", "Controlled trial of intravenous immune globulin in recent-onset dilated cardiomyopathy.", "Effect on neutrophil kinetics and serum opsonic capacity of intravenous administration of immune globulin to neonates with clinical signs of early-onset sepsis.", "Randomized study of subcutaneous low molecular weight heparin plus aspirin versus intravenous immunoglobulin in the treatment of recurrent fetal loss associated with antiphospholipid antibodies.", "Multicenter study to assess safety and efficacy of INH-A21, a donor-selected human staphylococcal immunoglobulin, for prevention of nosocomial infections in very low birth weight infants." ]	[ "To determine whether therapy with intravenous immunoglobulin G (IVIG) would decrease mortality in neonatal sepsis.\n Three tertiary care neonatal intensive care units in the city of Bangalore.\n All neonates admitted to the Neonatal Intensive Care Units with the clinical diagnosis of sepsis and having at least C-reactive protein and one other rapid diagnostic criteria positive were enrolled. Neonates with a birth weight of less than 1000 g and those with any major congenital malformation were excluded. The neonates were randomized to receive 1 g/kg of IVIG on three consecutive days or an equivalent amount of placebo. The rest of the treatment including antibiotics and supportive care was as per the treating physician's decision. The main outcome variable was survival.\n The trial was carried out over a period of 8 months and recruited 58 neonates. Seven neonates who qualified but did not receive either IVIG or placebo were taken into a separate control group, and one baby who received only one dose of IVIG was excluded from the analysis. Twenty-five neonates were enrolled into the IVIG arm and 25 in the placebo arm. The neonates in the therapy and placebo groups were comparable in terms of birth weight (2144+/-675 g vs. 2072+/-682 g), gestation (37.0+/-3.56 vs. 35.8+/-3.52 weeks), sex distribution, duration of stay, and number requiring ventilation. The placebo group had a significantly higher number of babies with positive blood culture. Seven babies in each group died (p>0.05). There was no significant benefit in using IVIG (OR 1.0; 95% CI 0.25-4.07) (p = 0.74).\n In the sample studied therapy with IVIG did not reduce mortality in neonatal sepsis", "Intravenous immunoglobulin as an adjunctive treatment in sepsis was regarded as promising by a Cochrane meta-analysis of smaller trials. In this phase III multicenter trial, we assessed whether intravenous immunoglobulin G (ivIgG) reduced 28-day mortality and improved morbidity in patients with score-defined severe sepsis.\n Randomized, double-blind, placebo-controlled, multicenter trial.\n Twenty-three medical and surgical intensive care units in university centers and large teaching hospitals.\n Patients (n = 653) with score-defined sepsis (sepsis score 12-27) and score-defined sepsis-induced severity of disease (Acute Physiology and Chronic Health Evaluation II score 20-35).\n Patients were assigned to receive either placebo or ivIgG (day 0, 0.6 g/kg body weight; day 1, 0.3 g/kg body weight).\n The prospectively defined primary end point was death from any cause after 28 days. Prospectively defined secondary end points were 7-day all-cause mortality, short-term change in morbidity, and pulmonary function at day 4. Six hundred fifty-three patients from 23 active centers formed the intention-to-treat group, 624 patients the per-protocol group (placebo group, n = 303; ivIgG group, n = 321). The 28-day mortality rate was 37.3% in the placebo group and 39.3% in the ivIgG group and thus not significantly different (p = .6695). Seven-day mortality was not reduced, and 4-day pulmonary function was not improved. Drug-related adverse events were rare in both groups. Exploratory findings revealed a 3-day shortening of mechanical ventilation in the surviving patients and no effect of ivIgG on plasma levels of interleukin-6 and tumor necrosis factor receptors I and II.\n In patients with score-defined severe sepsis, ivIgG with a total dose of 0.9 g/kg body weight does not reduce mortality.", "A total of 76 premature newborn infants with gestational age of 34 weeks or less were enrolled in a randomized controlled study to determine whether intravenously administrated immunoglobulin (IVIG) is able to prevent nosocomial sepsis. Forty infants were given 0.5 g/kg IVIG on the first day of life and 36 infants with similar gestational age and birth weight were selected as controls and did not receive IVIG. The frequency of proven sepsis, with a positive blood and/or cerebrospinal fluid culture, was significantly lower in infants who received IVIG as compared to controls (42.5 vs 80.0%) (p < 0.01). The mortality rate attributable to infection was not different in IVIG recipients and in controls (41 vs 48%) (p > 0.05). The overall mortality rates in the two groups were not different either (35.0 vs 44.4%) (p > 0.05). The majority of micro-organisms isolated from the blood culture of the patients were gram negative microorganisms (Klebsiella, Enterobacter). IVIG therapy was believed to be effective for prophylaxis of nosocomial infection, but such therapy was not able to reduce overall mortality rate or mortality rate due to systemic infection in prematurely born infants in our intensive care unit where the causative pathogens are usually gram negative microorganisms.", "The objective of this study was to assess the impact on outcome of adjuvant therapy (high-dose of immunoglobulin [Ig] M-enriched intravenous Ig, IVIG) in intensive care unit (ICU) patients who underwent surgery by abdominal sepsis. This was a prospective, randomized, double-blind, controlled study set in the medical/surgical ICUs of seven teaching hospitals. Patients with severe sepsis and septic shock of intra-abdominal origin admitted to the ICU within 24 h after the onset of symptoms were included in the study. Polyvalent IgM-enriched Ig (Pentaglobin; IVIG group) at a dosage of 7 mL/kg/day for 5 days or an equal amount of 5% human albumin (control group) was randomized. Fifty-six patients were enrolled. The overall mortality rate was 37.5.%. Twenty patients had shock and 36 had severe sepsis (the mortality rate was 55.0% and 25.0%, respectively). In the intent-to-treat analysis, the mortality rate was reduced from 48.1% in patients treated with antibiotic (ATB) plus albumin to 27.5% (P = 0.06) for patients with ATB plus IVIG. The organ failure score (1.0 +/- 0.6 vs. 1.2 +/- 0.9), organ dysfunction score (1.7 +/- 1.1 vs. 1.8 +/- 1.0), and reoperation rate (17.2% vs. 29.6%) were not different between IVIG and control groups, respectively. Eight patients (14.3%) received inappropriate ATB initial therapy (IAT), and seven died (87.5%). IAT was the only variable independently associated with death (odds ratio, 19.4) in a logistic regression model. We conclude that IVIG administration, when used in combination with adequate antibiotics, improved the survival of surgical ICU patients with intra-abdominal sepsis. The initial choice of antibiotic has a dramatic impact on outcome.", "Newborn infants may have IgG deficiencies that increase their susceptibility to bacterial infection. To determine whether intravenous immune globulin (IVIG) therapy improves survival rates in early-onset sepsis, we prospectively entered 753 neonates (birth weight 500 to 2000 gm, gestation less than or equal to 34 weeks, age less than or equal to 12 hours) into a multicenter, double-blind, controlled trial. Blood culture specimens were obtained and infants randomly assigned to receive 10 ml (per kilogram) intravenously of a selected IVIG (500 mg/kg) or albumin (5 mg/kg) preparation. Maternal and neonatal risk factors were not different between groups. Thirty-one babies (4.2%) had early-onset sepsis; the causative organisms were group B streptococcus (12 babies), Escherichia coli (6), and others (13). Of these 31 neonates, 7 (23%) died. Total serum IgG was higher for 7 days after IVIG therapy than after albumin treatment (p less than 0.05). During these 7 days, 5 (30%) of 17 albumin-treated and none of 14 IVIG-treated patients died (p less than 0.05). The survival rate at 56 days of age, however, was not significantly improved. Group B streptococcus type-specific IgG antibody was significantly increased after IVIG treatment and appeared to be related to the amount of IVIG specific antibody. Infusion-related adverse reactions were less frequent in patients receiving IVIG therapy (0.5%) than in those receiving albumin. The IVIG therapy in neonates with early-onset sepsis, while reducing the early mortality rate, did not significantly affect the overall survival rate. Further studies are necessary to confirm these findings and to determine more effective therapeutic regimens.", "To evaluate the use of intravenously administered immune globulin (IVIG) for prevention of sepsis in preterm infants, we administered IVIG in a protocol designed to maintain a therapeutic serum \"target level\" of 700 mg/dl. The 200 patients who were eligible for the study (600 to 2000 gm birth weight) were monitored throughout their initial hospitalization. Of these, 115 patients were randomly assigned in a double-blind, controlled trial to treatment and placebo groups. The remaining 85 infants were not randomly assigned to a group, by parental request, but were followed and analyzed separately. In one patient who received IVIG, transient tachycardia and a decrease in blood pressure developed during an infusion; resolution occurred promptly after the infusion was discontinued. No persistent hepatic or renal abnormalities were noted in either the IVIG- or the placebo-treated group. There were seven episodes of sepsis in the placebo group and nine in the group whose parents refused consent to the study. No infant who received IVIG acquired nosocomial sepsis (p less than 0.01). All patients in the placebo group in whom sepsis developed had serum IgG levels less than 400 mg/dl at the time sepsis developed. Serum IgG levels were maintained near 700 mg/dl in patients who received IVIG. These data indicate that administration of sufficient IVIG to maintain target serum IgG levels throughout hospitalization may decrease the incidence of nosocomial sepsis in preterm infants.", "The efficacy of intravenous immunoglobulin (IVIG) as prophylaxis for late sepsis was evaluated in a placebo-controlled, randomized, double-blind trial involving 240 infants of very low birth weight (less than 1,300 g). Each infant received a total of five doses of either IVIG (1 g/d) or an albumin placebo. The first four doses were administered between days 1 and 5 of life, and the last dose was administered on day 15 or shortly thereafter. Preliminary analysis of data available for 126 patients showed that in the first 30 days, sepsis developed in nine of 61 patients given IVIG and in 16 of 65 given placebo (one-tailed P = .065). At 70 days, the number who developed sepsis was similar in the two groups: 20 for those who received IVIG vs. 23 for those who received placebo. When patients with coagulase-negative staphylococcal infections were deleted from the totals, the results were essentially the same, i.e., three of 61 who received IVIG vs. nine of 65 who received placebo (one-tailed P = .041), developed sepsis during the first 30 days and 12 of 61 vs. 13 of 65, respectively, had developed sepsis at 70 days. In the IVIG group, the median peak level of serum IgG at day 7 was 1,700 mg/dL and the IgG levels were significantly greater than those in the placebo group for days 7-42. These data suggest that infusions of IVIG at the doses and dosing intervals used in this study may be effective in decreasing the incidence of late-onset sepsis during the first month of life in infants of very low birth weight.", "The efficacy and safety of high-dose intravenous polyspecific immunoglobulin G (IVIG) as adjunctive therapy in streptococcal toxic shock syndrome (STSS) were evaluated in a multicenter, randomized, double-blind, placebo-controlled trial. The trial was prematurely terminated because of slow patient recruitment, and results were obtained from 21 enrolled patients (10 IVIG recipients and 11 placebo recipients). The primary end point was mortality at 28 days, and a 3.6-fold higher mortality rate was found in the placebo group. A significant decrease in the sepsis-related organ failure assessment score at days 2 (P=.02) and 3 (P=.04) was noted in the IVIG group. Furthermore, a significant increase in plasma neutralizing activity against superantigens expressed by autologous isolates was noted in the IVIG group after treatment (P=.03). Although statistical significance was not reached in the primary end point, the trial provides further support for IVIG as an efficacious adjunctive therapy in STSS.", "To determine whether a single dose of intravenously administered immune globulin (IVIG) decreases late-onset sepsis in premature infants, we prospectively entered 753 neonates with birth weight 500 to 2000 gm, gestation < or = 34 weeks, and age < or = 12 hours into a multicenter, double-blind, controlled trial. Infants were randomly selected to receive a single intravenous infusion, 10 ml/kg, of either IVIG (500 mg/kg) or albumin (5 mg/kg) and were observed for 8 weeks for infection. Maternal and neonatal risk factors for infection did not differ between groups. Although serum IgG values before infusion were related to gestation (R = 0.62), the change in serum IgG or half-life of IgG after IVIG infusion was not (R < or = 0.09). The serum IgG concentration was increased (p < 0.05) in IVIG-treated patients for 8 weeks. There were 88 episodes of late-onset sepsis in 79 neonates (10.5%). Causative organisms included the following: Staphylococcus epidermidis (37 episodes), Enterococcus (9), Staphylococcus aureus (7), Candida (6), Escherichia coli (6), and multiple organisms (11). Sepsis, death, and death as a result of infection were unaffected by treatment. We conclude that a single infusion of IVIG, 500 mg/kg, shortly after birth was not effective prophylaxis for late-onset infection in premature neonates. Future studies of late-onset sepsis prophylaxis should consider IVIG with known pathogen-specific antibody concentrations against organisms causing these infections, in particular S. epidermidis.", "To evaluate the effect of intravenous IgMA-enriched immunoglobulin (ivIGMA) therapy on mortality in neutropenic patients with hematologic malignancies and sepsis syndrome or septic shock.\n Multiple-center, prospective randomized, controlled study.\n Six university hospitals in Germany.\n Patients were 211 neutropenic patients with sepsis syndrome or septic shock after chemotherapy for severe hematologic disorders between 1992 and 1999.\n Patients received 1300 mL of ivIGMA (7.8 g IgM, 7.8 g IgA, and 49.4 g IgG) infused intravenously within a period of 72 hrs or human albumin according to the same schedule as ivIGMA.\n All-cause mortality at 28 days, sepsis-related mortality at 28 days, all-cause mortality at 60 days, mortality from septic shock, and mortality from microbiologically proven Gram-negative sepsis and septic shock were recorded. Immunoglobulin had no benefit over human albumin. The 28-day mortality rate was 26.2% and 28.2% in the ivIGMA and control patients, respectively (difference, 2.0% [95% confidence interval, -10.2 to 14.2 percentage points]). Likewise, the 60-day mortality rate did not differ between both arms (29.6% vs. 34.7% in the ivIGMA and control patients, respectively). Mortality rates in patients with sepsis syndrome (17.1% vs. 16.7%) and septic shock (51.9% vs. 54.8%) were also found to be similar between both groups.\n Intravenous ivIGMA had no beneficial effects in neutropenic patients with hematologic malignancies and sepsis syndrome and septic shock.", "Despite the development of newer generation of antibiotics, mortality from neonatal sepsis remains high. In a prospective, randomized study, we investigated the use of IgM-enriched immunoglobulin therapy in neonatal sepsis. Two groups of 30 infants each (matched for gestational age, sex, weight, and other variables) were randomly allocated to receive either antibiotics alone (control group) or antibiotics plus 5 mL/kg/d for four days of IgM-enriched immunoglobulin intravenously (immunotherapy group). Mortality from sepsis in the control group was 20% (6/30), while in the immunotherapy group it was 3.3% (1/30). We conclude that IgM-enriched immunoglobulin therapy in conjunction with antibiotic therapy significantly reduces mortality from neonatal sepsis.", "The aim of this study was to investigate whether intravenous immunoglobulin (IVIG) can prevent sepsis in premature newborn infants. The study group consisted of 80 preterm newborn infants, who were divided into two groups: 40 preterm newborns received IVIG prophylactically (group A) and the control group (group B, n = 40) did not receive IVIG. IVIG was given at a dose of 500 mg/kg to infants. weighing greater than 1500 g, and 700 mg/kg to those weighing less than 1500 g at birth on days one, two and eight of life. By two, eight and 12 days of age, the treatment group had significantly greater IgG concentrations than the control group. Mortality was 7.5 percent (3/40) in group A and 27.5 percent (11/40) in group B (p < 0.01). Bacteremia was determined in three blood cultures in group A and eight in group B, particularly S.aureus and S.enteritis.", "To evaluate the safety and potential efficacy of antithrombin III (AT III) in reducing mortality in patients with severe sepsis.\n Prospective, randomized, placebo-controlled, double-blind, phase II, multicenter, multinational clinical trial.\n Seven academic medical center intensive care units (ICU) in Belgium, Denmark, the Netherlands, Norway and Sweden.\n 42 patients with severe sepsis who received standard supportive care and antimicrobial therapy, in addition to the administration of AT III or placebo.\n Patients received either an intravenous loading dose of 3000 IU AT III followed by a maintenance dose of 1500 IU every 12 h for 5 days or equivalent amounts of placebo.\n All patients were evaluated for safety and for 30-day all-cause mortality.\n The administration of AT III was safe and well-tolerated. It was followed by a 39 % reduction in 30-day all-cause mortality (NS). The reduction in mortality was accompanied by a considerably shorter stay in the ICU. Patients treated with AT III exhibited a better performance in overall severity of illness and organ failure scores (Acute Physiology and Chronic Health Evaluation II, multiple organ failure, organ system failure), which was noticeable soon after initiation of treatment. Patients treated with AT III demonstrated a better resolution of pre-existing organ failures and a lower incidence of new organ failures during the observation period. A meta-analysis comprising this and two other double-blind, placebo-controlled trials with AT III with a total of 122 patients suffering from severe sepsis confirms the positive trend. The results of the meta-analysis demonstrate a 22.9 % reduction in 30-day all-cause mortality in patients treated with AT III. Although still too small to be confirmative, the meta-analysis clearly points to the fact that a sufficiently powered phase III trial is warranted to prove whether AT III has a beneficial role in the treatment of severe sepsis.", "In patients with relapsing-remitting multiple sclerosis (MS), IVIG was shown to reduce the relapse rate and progression of disability. In patients with chronic progressive MS, a beneficial effect of IVIG was not documented in placebo controlled studies. This trial investigated the influence of IVIG in primary (PPMS) and secondary (SPMS) chronic progressive MS. Two-hundred and thirty-one patients stratified for PPMS (n=34) and SPMS (n=197) were randomly assigned to IVIG 0.4 g/kg per month or to placebo for 24 months. Primary endpoints were 1) the time to sustained progression of disease identified as worsening of the expanded disability status scale (EDSS) sustained for 3 months, and 2) the improvement of neurological functions defined by a patient's best EDSS score. Secondary endpoints were the proportion of patients with sustained progression, the relapse rate, the assessment of fine motor skills, visual evoked potentials, contrast sensitivity, depression and quality of life. Analysis of the intention-to-treat (ITT) population of combined PPMS and SPMS patients showed that the mean time to sustained progression was 74 weeks in the IVIG compared with 62 weeks in the placebo group (P=0.0406). When PPMS and SPMS patients were analysed separately, the time to sustained progression was also longer in the IVIG group, but the difference was not significant. There was no IVIG-mediated improvement in neurological functions. In the combined per protocol (PP) treated patients, IVIG treatment prolonged time to sustained progression by 13 weeks (P=0.0396). PPMS patients, but not SPMS patients showed a slight favourable IVIG effect on the best EDSS score. In the combined ITT population there were less patients with sustained progression in the IVIG than in the placebo group (P=0.028). The difference was significant in PPMS (P=0.016), but not in SPMS patients. In the combined PP population, there was a trend for a favorable IVIG effect on the rates of patients with sustained progression. In patients with PPMS, this IVIG effect reached significance (P=0.036). Other secondary endpoints did not show significant differences between treatment groups. Eighteen patients with PPMS and 102 patients with SPMS withdrew from the study for various reasons. Treatment was generally well tolerated. It was concluded that monthly IVIG infusion could delay progression of disease in patients with PPMS, and that there was a trend in favour of IVIG treatment in patients with SPMS.", "To determine whether percutaneously inserted central venous catheters (PICC) and peripheral intravenous catheters (PIV) in infants with very low birth weight (VLBW) differ with respect to (1) incidence of sepsis, (2) number of insertion attempts and catheters required for total intravenous therapy, (3) courses of antibiotics, and (4) total duration of intravenous (IV) use.\n A randomized comparative trial was conducted involving 63 VLBW infants (<1,251 g) who required IV therapy. Infants were assigned randomly at 1 week of age to either a PIV or a PICC catheter and followed up prospectively until an IV was no longer required or the infant was transferred out of the neonatal intensive care unit.\n Data were analyzed on an intention-to-treat basis. There was no difference in the incidence of sepsis (P = .64), number of courses of antibiotics (P = .16), or total duration of IV use (P= .34) between the 2 groups. The number of insertion attempts required for total IV therapy was significantly lower in the PICC group than in the PIV group (P = .008). There also was a significantly lower number of total catheters utilized in the PICC group (P = .002). When data were controlled for birth weight strata the results were similar.\n PICC lines reduced the number of painful IV procedures in VLBW infants without additional morbidity.", "To assess the efficacy of adjunctive monoclonal antibody antiendotoxin immunotherapy in patients with gram-negative sepsis.\n Double-blind, randomized, placebo-controlled trial.\n Thirty-three university-affiliated centers, including Veterans Affairs, community, and municipal hospitals.\n Hospitalized adults with signs of gram-negative infection and a systemic septic response.\n Patients were assigned to receive either 2 mg/kg of a murine monoclonal antibody directed against gram-negative endotoxin (E5) or placebo. A second infusion was administered 24 hours later.\n Mortality over the 30-day study period, resolution of organ failures, and safety.\n Four hundred eighty-six patients were enrolled. Three hundred sixteen had confirmed gram-negative sepsis (54% bacteremic, 46% nonbacteremic). The survival difference was not statistically significant for all patients. Among patients with gram-negative sepsis who were not in shock at study entry (n = 137), E5 treatment resulted in significantly greater survival (relative risk, 2.3; P = .01). Resolution of individual organ failures was more frequent among these patients, occurring in 19 (54%) of 35 patients in the E5 group vs eight (30%) of 27 in the placebo group (P = .05). Four reversible allergic reactions occurred among 247 patients (1.6%) receiving E5. No other toxicity was identified.\n Treatment with E5 antiendotoxin antibody appears safe. It reduces mortality and enhances the resolution of organ failure among patients with gram-negative sepsis who are not in shock when treated.", "To determine the safety and efficacy of BAY x 1351, a murine monoclonal antibody to recombinant human tumor necrosis factor (TNF)-alpha, in patients with sepsis.\n An international, multicenter, prospective, placebo-controlled trial in patients with sepsis, stratified into shock/nonshock groups.\n Forty acute clinical care facilities in 14 countries.\n Of the 564 patients enrolled in the study, 553 patients received study drug or placebo.\n Patients received 15 mg/kg or 3 mg/kg of BAY x 1351, or placebo, as a single intravenous infusion.\n The patients were well matched for severity of illness and for risk factors known to influence the outcome of sepsis. There was no difference in 28-day mortality rates between groups (placebo group 66 [39.5%] of 167;3 mg/kg group 57 [31.5%] of 181; 15 mg/kg group 87 [42.4%] of 205). Approximately 9 months after this study had begun, an interim safety examination of NORASEPT, a North American Sepsis Trial using the same monoclonal antibody, indicated that there was no benefit to patients in the nonshock group and further enrollment of these nonshock septic patients into INTERSEPT was stopped. The analysis therefore focused on the 420 patients in shock. The primary efficacy variable was the 28-day, all-cause mortality rate: placebo group 57 (42.9%) of 133; 3-mg/kg group 51 (36.7%) of 139; and 15-mg/kg group 66 (44.6%) of 148 (not significant). Two secondary efficacy variables were identified prospectively: shock reversal and frequency of organ failures. Life-table analysis showed that in patients who survived 28 days, there was a more rapid reversal of shock in both treatment groups compared with placebo (15-mg/kg group vs. placebo group log-rank statistic p = .007, 3-mg/kg group vs. placebo group p = .01). Similarly, in patients surviving 28 days, there was a significant delay in the time to the onset of first organ failure (log rank 15 mg/kg vs. placebo p = .03, 3 mg/kg vs. placebo p = .07), and more patients in the placebo group developed at least one organ failure: 15-mg/kg group 33 (40.2%) of 82; 3-mg/kg group 39 (44.3%) of 88; and placebo group 45 (59.2%) of 76 (15 mg/kg vs. placebo p = .03, 3 mg/kg vs. placebo p = .06). No significant adverse events were associated with the monoclonal antibody treatment.\n INTERSEPT provides additional clinical data implicating TNF-alpha as an integral mediator of septic shock. The study suggested a possible role for anti-TNF antibody as adjunctive therapy, but this possibility requires confirmation by another clinical trial.", "The polyneuropathy associated with a monoclonal IgM directed to the myelin associated glycoprotein (MAG) is a specific entity with a putative causal link between the IgM and the neuropathy. The small benefit offered by alkylating agents or plasma exchanges in these patients justifies the search for alternative treatments.\n A 12 month multicentre, prospective, randomised, open clinical trial was carried out comparing intravenous immunoglobulin (IVIg; 2g/kg and then 1 g/kg every three weeks) and recombinant interferon-alpha (IFN-alpha; 3 MU/m2 subcutaneously three times weekly). The main end point was a clinical neuropathy disability score (CNDS) after six months of treatment. Twenty patients were enrolled; 10 were assigned to IVIg and 10 to IFN-alpha.\n At six months, one out of 10 patients treated with IVIg had a CNDS improvement of more than 20% whereas eight out of 10 patients treated with IFN-alpha had such an improvement (P=0.005). The mean CNDS worsened by 2.3 (SD 7.6) (8%) in the IVIg group whereas it improved by 7.5 (SD 11.1) (31%) in the IFN-alpha group (P=0.02). This improvement persisted after 12 months and was mainly related to an improvement of the sensory component (P=0.02) whereas the motor component was unchanged (P=0.39). Electrophysiological data did not show improvement of motor nerve conduction velocities whereas sensory nerve conduction velocities improved in the upper limbs. A decrease in the level of the monoclonal IgM was seen in two patients treated with IFN-alpha. At the end of the treatment, antibody activity to MAG was still detected in the serum of all patients.\n IVIg, as used in this study, did not improve patients with polyneuropathy and monoclonal IgM. By contrast, although its mechanism of action remains to be fully elucidated, IFN-alpha was effective in eight out of 10 patients at six months.", "The value of IgM-enriched immunoglobulin therapy in 44 preterm infants with neonatal sepsis was evaluated in a prospective randomized study. All infants received antibiotic therapy and fresh plasma and/or whole blood transfusions. Twenty randomly-chosen infants were allocated to receive 5 ml/kg/d of IgM-enriched immunoglobulin intravenously for three days. Although the mortality rate in preterm infants whose gestational ages were 31-34 weeks in the immunotherapy group was slightly lower than in the control group, the general mortality rate from sepsis in the control group (9/24) and in the immunotherapy group (6/20) showed no statistically significant difference (37.5% vs 30.0%, p < 0.05).", "In a recently reported study, low doses of intravenous immunoglobulins (IVIG) were shown to be as effective as high doses in protecting chronic lymphocytic leukemia (CLL) patients against infections, although a control group was not included. With this background we started a crossover study of low-dose IVIG prophylaxis aimed at investigating its superiority over empirical treatment of infections.\n Forty-two CLL patients with hypogammaglobulinemia (IgG < 600 mg/dL) and/or a history of at least one episode of severe infection in the 6 months preceding inclusion in the study were randomly allocated to receive either an infusion of 300 mg/kg IVIG every 4 weeks for 6 months or no treatment. Then they were switched to observation or IVIG for another 12 months; finally, they received IVIG or no therapy for 6 more months.\n A significantly lower incidence of infectious episodes was observed during IVIG prophylaxis in 30 patients who completed the 6-month period of either observation or IVIG therapy. The same applied to the 17 patients who completed 12 months of either observation or IVIG prophylaxis. Interestingly, the restoration of serum IgG levels obtained in 17 out of 25 patients (mean percent value of IgG increase, 41.8%) did not parallel a decrease in the number of infectious episodes.\n A protective effect against infections is demonstrated for low-dose IVIG in the present study. A benefit was shown in patients who completed either 12 or 6 months of IVIG prophylaxis; however, even this low-dose treatment is not a cost effective way to prevent infection in CLL patients.", "To determine whether adjunctive therapy with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) could reverse sepsis-associated neonatal neutropenia and improve neonatal survival and to assess its safety compared with conventional therapy in a control group.\n This prospective, randomized, controlled trial was performed in 60 infants with neutropenia and clinical signs of sepsis. A subcutaneous injection of rhGM-CSF (5 microgram/kg/day) was administered to 30 of the patients for 7 consecutive days. Hematologic parameters (absolute neutrophil, eosinophil, monocyte, lymphocyte counts, and platelet number) and outcome were compared with 30 conventionally treated (control) patients.\n Twenty-five patients from the GM-CSF-treated group and 24 from the conventionally treated group had early-onset sepsis (</=3 days' postnatal age), and the other 11 patients had late-onset sepsis (>3 days' postnatal age). There was no difference between groups in terms of birth weight; gestational age; gender; maturity; maternal age; and incidence of prolonged rupture of membranes, maternal hypertension, or severity of sepsis. All neonates tolerated GM-CSF well with no adverse reactions. The absolute neutrophil count on day 7 was significantly increased in the GM-CSF-treated group compared with the conventionally treated group: 8088 +/- 2822/mm(3) versus 2757 +/- 823/mm(3). The mean platelet count was significantly higher on days 14 in the GM-CSF-treated group compared with conventionally treated group: 266 867 +/- 55 102/mm(3) versus 229 200 +/- 52 317/mm(3). Hematologic parameters were otherwise similar between groups before treatment and on day 28. Twenty-seven neonates in the rh-GMCSF group and 21 in the control group survived to hospital discharge. The mortality rate in the rhGM-CSF group (10%) was significantly lower than in the conventionally treated group (30%).\n Treatment with rhGM-CSF is associated with an increase in absolute neutrophil, eosinophil, monocyte, lymphocyte, and platelet counts and decreased mortality in critically ill septic neutropenic neonates. These results suggest that rhGM-CSF may be effective in the treatment of neonatal sepsis with neutropenia, and further randomized trials are needed to confirm its beneficial effects.", "Nosocomial infections are a major cause of death in premature infants, especially in very low birthweight (VLBW) infants. The VLBW infants have low serum immunoglobulin G levels, which may have an effect on infections in early infancy. Thus, prophylactic administration of intravenous immunoglobulin (IVIG) is proposed to maintain higher immunoglobulin G and reduce the rate of hospital-acquired infection.\n A study for the effects of prophylactic IVIG therapy in VLBW infants was performed. A total of 61 VLBW infants were enrolled, and divided into the IVIG group (n = 31) and the control group (n = 30). The dose for each infant was 750-1000 mg/kg for those whose birthweight was less than 1000 g, and 500-750 mg/kg for infants whose birthweight was between 1001 and 1500 g. The control group received saline infusion. The infusions were given every 2 weeks until the infant weighed 1800 g, or was discharged.\n The results showed: there were no major differences in the perinatal and neonatal characteristics between the two groups, consistently higher IgG levels were found in the IVIG group, and the age of first documented sepsis was earlier in the control group.\n In this study, the prophylactic IVIG therapy may give substantially higher IgG levels, which may last for 2 months. However, a prophylactic effect for hospital-acquired infections was not observed.", "Neonatal sepsis is a major cause of death and complications despite antibiotic treatment. Effective adjunctive treatments are needed. Newborn infants are relatively deficient in endogenous immunoglobulin. Meta-analyses of trials of intravenous immune globulin for suspected or proven neonatal sepsis suggest a reduced rate of death from any cause, but the trials have been small and have varied in quality.\n At 113 hospitals in nine countries, we enrolled 3493 infants receiving antibiotics for suspected or proven serious infection and randomly assigned them to receive two infusions of either polyvalent IgG immune globulin (at a dose of 500 mg per kilogram of body weight) or matching placebo 48 hours apart. The primary outcome was death or major disability at the age of 2 years.\n There was no significant between-group difference in the rates of the primary outcome, which occurred in 686 of 1759 infants (39.0%) who received intravenous immune globulin and in 677 of 1734 infants (39.0%) who received placebo (relative risk, 1.00; 95% confidence interval, 0.92 to 1.08). Similarly, there were no significant differences in the rates of secondary outcomes, including the incidence of subsequent sepsis episodes. In follow-up of 2-year-old infants, there were no significant differences in the rates of major or nonmajor disability or of adverse events.\n Therapy with intravenous immune globulin had no effect on the outcomes of suspected or proven neonatal sepsis.", "ATIII is decreased in sepsis and/or shock and its baseline value correlates with mortality. The efficacy of ATIII therapy on mortality was assessed in a selected group of patients admitted to the intensive care unit (ICU) in a double-blind, randomized, multicenter study.\n 120 patients admitted to the ICU with an ATIII concentration < 70% were randomized to receive ATIII (total dose 24000 units) or placebo treatment for 5 days; 56 patients had septic shock.\n ATIII concentrations in the treated group remained constant throughout the treatment period (range 97-102%). The Kaplan-Meier analysis showed no difference in overall survival between the two groups: 50 and 46% for ATIII and placebo, respectively. Septic shock and hemodynamic support were unbalanced in the two groups at admission. Therefore the Cox analysis was carried out after adjusting for these two variables. Treatment with ATIII decreases the risk of death with an odds ratio (OR) of 0.56. Of the covariates analyzed, septic shock and the baseline multiple organ failure score were negatively associated with survival and plasma activity level was positively associated with survival with an OR of 0.97 for each 1% increase in the ATIII plasma concentration at baseline.\n The results of ATIII treatment in this population of patients suggests that replacement therapy reduces mortality in the subgroup of septic shock patients only.", "The primary objective was to investigate the safety of recombinant human granulocyte colony stimulating factor (rhG-CSF) for the treatment of very low birthweight infants (VLBW) with sepsis and relative neutropenia, specifically with regard to worsening of respiratory distress and thrombocytopenia and all cause mortality. Secondary objectives were to evaluate duration of ventilation, intensive care, and antibiotic use as markers of efficacy.\n Neonates (< or = 28 days) in intensive care, with birth weights of 500-1500 g, absolute neutrophil count (ANC) of < or = 5 x 10(9)/l, and clinical evidence of sepsis, were randomly assigned to receive either rhG-CSF (10 microg/kg/day) administered intravenously (n = 13), or placebo (n = 15) for a maximum of 14 days, in addition to standard treatment and antibiotics. All adverse events, oxygenation index, incidence of thrombocytopenia, all cause mortality, duration of ventilation, intensive care and antibiotic treatment, and ANC recovery were compared between the two groups.\n Adverse events and oxygenation index were not increased by, and thrombocytopenia was not attributable to, treatment with rhG-CSF. At 6 and 12 months postmenstrual age, there were significantly fewer deaths in the group receiving rhG-CSF (1/13 v 7/15; p < or = 0.038). There was a non-significant trend towards a reduction in duration of ventilation, intensive care, and antibiotic use in the rhG-CSF group. There was a significantly more rapid increase in ANC in the rhG-CSF treated babies (p < 0.001).\n In a small randomised placebo controlled trial in a highly selected group of neonates, adjuvant treatment with rhG-CSF increased ANC rapidly, and no treatment related adverse events were identified. Mortality at 6 and 12 months postmenstrual age was significantly lower in the treatment group. A large trial investigating efficacy in a similar group of neonates is warranted.", "Patients with a clinical diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) were randomised in a double-blind, placebo-controlled multicentre trial to investigate whether high-dose intravenous immunoglobulin treatment (IVIg) for 5 consecutive days has a beneficial effect. Fifteen patients were randomised to IVIg and 13 to placebo. In the IVIg treatment group 4 patients improved and 3 patients in the placebo group. The degree of improvement of the patients in the IVIg treatment group was no different from the patients in the placebo group. Electrophysiological studies did not show significant differences between the groups. Since a previously performed cross-over trial showed that a selected group of CIDP patients responded better to IVIg than to placebo, it is concluded that we need better criteria to select CIDP patients for treatment with IVIg.", "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.", "Efficacy of immunotherapy for treatment of recurrent spontaneous abortion (SA) has been controversial. The low treatment effect of white blood cell immunization lead to investigations of alternative treatments including intravenous (i.v.) immunoglobulin (Ig). To evaluate the efficacy of IVIg for treatment of recurrent SA, a prospective, randomized, double blinded, placebo-controlled trial was performed.\n Ninety-five women experiencing two or more consecutive spontaneous abortions, with no known cause were randomized and received either IVIg 500 mg/kg/month or placebo (albumin).\n Of 95 women participating in the study, 47 received IVIg and 48 received placebo. Medication was discontinued in 34 women who failed to conceive within four cycles. The remaining 61 women achieved pregnancy. Pregnancy outcomes included 29 deliveries and 32 recurrent SA. Among women delivering live births 18 (62%) received IVIg and 11 (38%) received placebo. By contrast, 21 (66%) women experiencing recurrent SAs received placebo and 11 (34%) received IVIg. Among 61 women who conceived, 29 received IVIg and 32 received placebo. Of the 29 women who conceived and received IVIg, 18 (62%) delivered live births and 11 (38%) experienced recurrent SA. Of 32 women who conceived and received placebo 11 (34%) delivered live births and 21 (66%) had recurrent SA. The difference in live birth rates between women receiving IVIg and placebo was significant (P = 0.04, odds ratio 3.1).\n IVIg is effective in enhancing the percentage of live births among women experiencing unexplained recurrent SA.", "In this prospective, randomized controlled study, we aimed to evaluate the effect of IgM-enriched immunoglobulin treatment on progression of organ failure and septic shock in patients with severe sepsis.\n Forty-two patients with severe sepsis were enrolled in the study. Patients in the study group (n = 21) received an intravenous immunoglobulin preparation (Pentaglobin in addition to standard therapy. Pentaglobin therapy was commenced on the day of diagnosis of severe sepsis: 5 ml/kg per day Pentaglobin (38 g/l IgG, 6 g/l IgM, and 6 g/l IgA) was infused over 6 hours and repeated for 3 consecutive days. Patients in the control group (n = 18) received standard sepsis therapy, but no immunoglobulin administration. Blood samples for procalcitonin (PCT) measurements were taken daily for 8 days. Severity of critical illness and development of organ failure were assessed by obtaining daily acute physiological and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores.\n Procalcitonin levels showed a statistically significant decrease in the Pentaglobin group (P < 0.001); however, an improvement in SOFA scores could not be demonstrated. Procalcitonin levels and SOFA scores did not change significantly in the control group. Septic shock incidence (38% versus 57%) and 28-day mortality rate (23.8% versus 33.3%) were found to be similar between the Pentaglobin and control groups. The evaluation of serial APACHE II scores did not demonstrate a difference between Pentaglobin and control groups either.\n Present data could not demonstrate any beneficial effects of polyclonal immunoglobulin preparation Pentaglobin on organ morbidity, septic shock incidence and mortality rate in patients with severe sepsis.", "Recent observations have shown that treatment with high-dose intravenous gammaglobulin (IVIgG) given to the mother may improve fetal outcome in cases of severe Rh D alloimmunization. Unfortunately, the costs of this new method of treatment are too high for routine use. Therefore, we decided to apply this treatment to the fetus and to investigate whether the effect of IVIgG might be attributable to blockade of the fetal mononuclear phagocyte system. We have performed a randomized study in which 20 fetuses with severe Rh D-haemolytic disease (HDN) were treated with intrauterine intravascular red cell transfusions (IUT). In 10 of these 20 cases transfusions were followed by administration to the fetus of low-dose IVIgG (85.7 +/- 11.6 mg/kg by ultrasound-estimated fetal weight because of fetal vascular volume considerations). We compared the number of IUTs, postnatal exchange transfusions, haematocrit (Ht) and haemoglobulin (Hb) values before and after transfusion (s) needed by the newborns of the two groups. No significant differences in the transfusion requirements of the fetuses and in the clinical outcome could be demonstrated. However, the 95% confidence interval for the difference in the improvement of cord blood Ht was too wide for any conclusions. The 95% confidence interval for the difference in the improvement of Hb levels suggests that any clinically relevant advantage of IVIgG on Hb is unlikely.", "To determine whether intravenous immunoglobulin (IVIG) prevents severe infections during autologous bone marrow transplantation or equivalent high-dose myelosuppressive therapy.\n Randomized, stratified, nonblinded study.\n Three tertiary care university hospitals.\n One hundred seventy patients entered the study; 82 received IVIG and 88 were untreated controls. The study groups were similar for parameters capable of influencing the likelihood of infection.\n Intravenous immunoglobulin was given weekly at a dose of 500 mg/kg body weight from the initiation of cytotoxic therapy to the resolution of neutropenia.\n The development of bloodstream or other clinically proven infection, platelet use, and the development of alloimmunity to platelet transfusion.\n Clinical infection, bacteremia, and fungemia occurred in 43%, 35%, and 6% of the IVIG-treated patients and in 44%, 34%, and 9% of the control patients. Gram-positive bacteremia and gram-negative bacteremia occurred in 28% and 11% of the IVIG group and in 23% and 13% of the control group. Death due to infection occurred in 4.9% of IVIG recipients and in 2.3% of controls. None of these observations was statistically significant (P > 0.2). Survival to hospital discharge was achieved in 86.6% of the IVIG group and in 96.6% of the control group. The survival difference (10%; 95% CI, 1.7% to 18.3%; P = 0.02) was due to a higher incidence of regimen-related toxic death in the IVIG-treated group.\n The use of IVIG did not prevent infection. Fewer deaths occurred among controls due to a higher incidence of fatal hepatic veno-occlusive disease in patients receiving IVIG.", "This prospective placebo-controlled trial was designed to determine whether intravenous immune globulin (IVIG) improves left ventricular ejection fraction (LVEF) in adults with recent onset of idiopathic dilated cardiomyopathy or myocarditis.\n Sixty-two patients (37 men, 25 women; mean age +/-SD 43.0+/-12.3 years) with recent onset (</=6 months of symptoms) of dilated cardiomyopathy and LVEF </=0.40 were randomized to 2 g/kg IVIG or placebo. All underwent an endomyocardial biopsy before randomization, which revealed cellular inflammation in 16%. The primary outcome was change in LVEF at 6 and 12 months after randomiz. Overall, LVEF improved from 0.25+/-0.08 to 0.41+/-0.17 at 6 months (P<0.001) and 0.42+/-0.14 (P<0.001 versus baseline) at 12 months. The increase was virtually identical in patients receiving IVIG and those given placebo (6 months: IVIG 0.14+/-0.12, placebo 0.14+/-0.14; 12 months: IVIG 0.16+/-0.12, placebo 0.15+/-0.16). Overall, 31 (56%) of 55 patients at 1 year had an increase in LVEF >/=0.10 from study entry, and 20 (36%) of 56 normalized their ejection fraction (>/=0.50). The transplant-free survival rate was 92% at 1 year and 88% at 2 years.\n These results suggest that for patients with recent-onset dilated cardiomyopathy, IVIG does not augment the improvement in LVEF. However, in this overall cohort, LVEF improved significantly during follow-up, and the short-term prognosis remains favorable.", "This study was designed to test the hypothesis that administration of immune globulin to human neonates with early-onset bacterial sepsis would (1) facilitate neutrophil egress from the marrow, (2) improve serum opsonic capacity, and (3) facilitate recovery from the infectious illness. Twenty-two newborn infants with clinical signs of early-onset sepsis were given an intravenous infusion of either 750 mg of immune globulin (IVIG) per kilogram of body weight or the same volume of a vehicle control (albumin). All 22 infants survived, but significant hematologic, immunologic, and respiratory differences were observed after the IVIG and not after the control infusion. Eleven of the patients had neutropenia; 24 hours after the infusions, the neutropenia had resolved in all six IVIG recipients but persisted in all five control recipients (p less than 0.001). Ten patients had I/T neutrophil ratios (a measure of immature neutrophils to total neutrophils on the leukocyte differential count) of less than 0.2. One hour after completion of the infusions, all five IVIG recipients had elevated I/T ratios (mean +/- SEM:0.10 +/- 0.05 before vs 0.43 +/- 0.03 after infusion; p less than 0.001), suggesting a prompt release of neutrophils from the marrow neutrophil storage pool into the circulation; no increase in the I/T ratio was observed in the control recipients. Six hours after the IVIG infusions, the ratio of arterial oxygen tension to fraction of inspired oxygen increased; no increase was observed after control infusions. Serum concentrations of IgG, IgG1, IgG2, IgG3, IgG4, and total hemolytic complement and the capacity of serum to support opsonophagocytosis of type II and type III group B streptococci increased markedly in the IVIG recipients but not in the control subjects. We conclude that administration of 750 mg IVIG per kilogram to neonates with clinical signs of early-onset sepsis was associated with immunologic, hematologic, and physiologic improvement.", "To compare the 2 most efficacious therapeutic regimens, intravenous immunoglobulin (IVIG) and anticoagulation with low molecular weight (LMW) heparin plus low-dose aspirin, in women with recurrent pregnancy loss associated with antiphospholipid antibodies (aPL).\n We examined 40 women with recurrent abortion (at least 3 occurrences) and repeatedly positive test results for anticardiolipin or lupus anticoagulant. The subjects were randomly assigned to treatment with IVIG or LMW heparin plus low-dose aspirin. Both therapies were started when the women were pregnant as documented by a positive urine test. IVIG was stopped at the thirty-first week of gestation, aspirin at the thirty-fourth week, and heparin at the thirty-seventh week. The primary outcome of interest was the rate of live births with the 2 treatments.\n The characteristics of the 2 groups were similar at the time of randomization. The women treated with LMW heparin plus low-dose aspirin had a higher rate of live births (84%) than those treated with IVIG (57%).\n Treatment with LMW heparin plus low-dose aspirin should be considered as the standard therapy for recurrent pregnancy loss due to aPL.", "Prophylactic administration of intravenous immunoglobulin has been inconsistent in reducing the risk of sepsis in very low birth weight (VLBW) infants presumably because of varying titers of organism specific IgG antibodies. INH-A21 is an intravenous immunoglobulin from donors with high titers of antistaphylococcal antibodies. This dose-ranging study explored safety and preliminary activity of INH-A21 for prevention of staphylococcal sepsis in VLBW infants.\n This was a multicenter, double blind, group-sequential study. Infants with birth weights 500-1250 g were randomized to receive up to 4 doses of placebo, 250 mg/kg, 500 mg/kg or 750 mg/kg INH-A21. Safety and frequencies of sepsis were compared across treatment groups.\n All treatment groups had similar mean gestational age, birth weight, Apgar score and maternal use of antibiotics. Randomizations to 250 mg/kg (N = 94) and 500 mg/kg (N = 96) doses were terminated after interim analyses demonstrated a low probability of finding a difference when compared with placebo. Infants randomized to the INH-A21 750 mg/kg group (N = 157) had fewer episodes of Staphylococcus aureus sepsis [relative risk (RR), 0.37; 95% confidence interval (CI), 0.12-1.12; P = 0.14], candidemia (RR 0.34; 95% CI 0.09-1.22; P = 0.09) and mortality (RR 0.64; 95% CI 0.25-1.61; P = 0.27) when compared with the placebo-treated cohort (N = 158). No dose-related trends were observed for adverse events or morbidities associated with prematurity.\n INH-A21 750 mg/kg demonstrated potential to reduce sepsis caused by S. aureus, candidemia and mortality in VLBW infants. Although statistical significance was not reached, based on the magnitude of the estimated differences, the efficacy and safety of INH-A21 750 mg/kg should be evaluated in an adequately powered, well-controlled study." ]	Polyclonal IVIG reduced mortality among adults with sepsis but this benefit was not seen in trials with low risk of bias. Among neonates, no reduction in mortality was seen with polyclonal IVIG. Most of the trials were small and the totality of the evidence is insufficient to support a robust conclusion of benefit. Adjunctive therapy with monoclonal IVIGs remains experimental.
CD004383	[ "12390903", "12399344", "11437861", "16053592", "15668310", "7953031", "11742777" ]	[ "Randomised controlled trial comparing an acute paediatric hospital at home scheme with conventional hospital care.", "Randomised controlled trial of home based care of patients with chronic obstructive pulmonary disease.", "Evaluation of a hospital diabetes specialist nursing service: a randomized controlled trial.", "The effectiveness, acceptability and costs of a hospital-at-home service compared with acute hospital care: a randomized controlled trial.", "Effects of a multidisciplinary, post-discharge continuance of care intervention on quality of life, discharge satisfaction, and hospital length of stay: a randomized controlled trial.", "Home-based versus hospital-based care for people with serious mental illness.", "Substitution of a nursing-led inpatient unit for acute services: randomized controlled trial of outcomes and cost of nursing-led intermediate care." ]	[ "To assess the clinical effectiveness of a paediatric hospital at home service compared to conventional hospital care.\n A total of 399 children suffering from breathing difficulty (n = 202), diarrhoea and vomiting (n = 125), or fever (n = 72) were randomised to Hospital at Home or in-patient paediatric care. Main outcome measures were: comparative clinical effectiveness as measured by readmission rate within three months (used as a proxy for parental coping with illness); and length of stay/care and comparative satisfaction of both patients and carers.\n Clinical effectiveness of both services was not significantly different. Length of care was one day longer in the Hospital at Home group; however, most parents and children preferred home care.\n Hospital at Home is a clinically acceptable form of care for these groups of acute paediatric illness. Readmission rates within three months failed to show any advantage in terms of parental coping. Parents and patients expressed a strong preference for hospital at home.", "To evaluate usefulness of limited community based care for patients with chronic obstructive pulmonary disease after discharge from hospital. Design: Randomised controlled trial.\n Liverpool Health Service and Macarthur Health Service in outer metropolitan Sydney between September 1999 and July 2000.\n 177 patients randomised into an intervention group (84 patients) and a control group (93 patients) which received current usual care.\n Home visits by community nurse at one and four weeks after discharge and preventive general practitioner care.\n Frequency of patients' presentation and admission to hospital; changes in patients' disease-specific quality of life, measured with St George's respiratory questionnaire, over three months after discharge; patients' knowledge of illness, self management, and satisfaction with care at discharge and three months later; frequency of general practitioner and nurse visits and their satisfaction with care.\n Intervention and control groups showed no differences in presentation or admission to hospital or in overall functional status. However, the intervention group improved their activity scores and the control group worsened their symptom scores. While intervention group patients received more visits from community nurses and were more satisfied with their care, involvement of general practitioners was much less (with only 31% (22) remembering receiving a care plan). Patients in the intervention group had higher knowledge scores and were more satisfied. There were no differences in general practitioner visits or management.\n This brief intervention after acute care improved patients' knowledge and some aspects of quality of life. However, it failed to prevent presentation and readmission to hospital.", "To evaluate the effectiveness and cost implications of a hospital diabetes specialist nursing service.\n We conducted a prospective, open, randomized, controlled trial of standard in-patient care for adults with diabetes, with and without the intervention of a diabetes specialist nursing (DSN) service. The setting was a single UK university hospital.\n were unselected patients referred to the hospital DSN service. Primary outcome measures were length of hospital stay and patterns of readmission (frequency and time to first readmission). Secondary outcome measures were subjects' diabetes-related quality of life, diabetes knowledge score, satisfaction with treatment, and GP and community care contacts following discharge. Costs were estimated from the hospital and published sources.\n Median length of stay was lower in the intervention group (11.0 vs. 8.0 days, P < 0.01). Readmission rates were the same in the two groups (25%), and mean time to readmission was similar in the two groups, although slightly less in the control group (278 vs. 283 days, P = 0.80). The cost per patient for nursing input was 38.94 pounds sterling. However, when the reduced length of stay was accounted for, the intervention produced a mean cost per admission of 436 ponds sterling lower than that of the control group (P = 0.19). Patients in the intervention group were more knowledgeable regarding their diabetes and more satisfied with their care.\n Diabetes specialist nurses are potentially cost saving by reducing hospital length of stay (LOS). There was no evidence of an adverse effect of reduced LOS on re-admissions, use of community resources, or patient perception of quality of care.", "To compare the safety, effectiveness, acceptability and costs of a hospital-at-home programme with usual acute hospital inpatient care.\n Patients aged 55 years or over being treated for an acute medical problem were randomized to receive either standard inpatient hospital care or hospital-at-home care. Follow-up was for 90 days after randomization. Health outcome measures included physical and mental function, self-rated recovery, health status as assessed by the SF-36, adverse events and readmissions to hospital. Acceptability was assessed using satisfaction surveys and the Carer Strain Index. Costs comprised hospital care, care in the home, community services, general practitioner services and personal health care expenses.\n In all, 285 people were randomized with a mean age of 80 years. There were no significant differences in health outcome measures between the two randomized groups. Significantly more patients receiving care at home reported high levels of satisfaction, as did more of their relatives. Relatives of the care-at-home group also reported significantly lower scores on the Carer Strain Index. However, the mean cost per patient was almost twice for patients treated at home (NZ 6524 dollars) as for standard hospital care (NZ 3525 dollars). A sensitivity analysis indicated that, if the service providing care in the home had been operating at full capacity, the mean cost per patient episode would have been similar for both modes of care.\n This hospital-at-home programme was found to be more acceptable and as effective and safe as inpatient care. While caring for patients at home was significantly more costly than standard inpatient care, this was largely due to the hospital-at-home programme not operating at full capacity.", "To determine the impact of a hospital-coordinated discharge care plan, involving a multidisciplinary team of primary health care providers, on hospital length of stay, quality of life, and both patient and general practitioner inclusion in, and satisfaction with, discharge procedures.\n This investigation comprised a prospective, randomized, controlled, clinical trial.\n This multicentre and cross-jurisdictional study focused on areas of tertiary and primary health care as well as community allied health in Western Australia.\n Patients (n = 189) with chronic cardiorespiratory diagnoses were recruited from respiratory, cardiovascular, and general medical wards at two tertiary hospitals.\n Subjects were randomly assigned to one of two groups. Intervention group patients received a discharge care plan in accordance with that outlined in the Australian Enhanced Primary Care Package, completed before discharge and sent to the patient's general practitioner and other community service providers for review. Control patients were discharged under existing hospital processes. Outcome measures. Patients and general practitioners were surveyed pre-discharge and 7 days post-discharge for quality of life and opinion of discharge procedures. Hospital length of stay was also determined.\n Significant improvements in discharge planning involvement, health service access, confidence with discharge procedures, and opinion of discharge based on previous experience were seen for patients who received the discharge care plan. Further, improved perceptions of mental quality of life were observed within the first week post-discharge for intervention patients. Length of stay showed no difference between groups. Extent and speed of hospital-general practitioner communication were significantly improved via the intervention.\n Our results indicate that a multidisciplinary discharge care plan, initiated before separation, improves quality of life, involvement, and satisfaction with discharge care, and hospital-general practitioner integration. As such, it possesses benefits over current Western Australian hospital discharge procedures for the care of chronically ill populations.", "A controlled study tested whether the superior outcome of community care for serious mental illness (SMI) in Madison and in Sydney would also be found in inner London.\n Patients from an inner London catchment area who faced emergency admission for SMI (many were violent or suicidal) were randomised to 20 months or more of either home-based care (Daily Living Programme, DLP; n = 92), or standard in-patient and later out-patient care (controls, n = 97). Most DLP patients had brief in-patient stays at some time. Measures included number and duration of in-patient admissions, independent ratings of clinical and social function, and patients' and relatives' satisfaction.\n Outcome was superior with home-based care. Until month 20, DLP care improved symptoms and social adjustment slightly more, and enhanced patients' and relatives' satisfaction. From 3 to 18 months DLP care greatly reduced the number of in-patient bed days as long as the DLP team was responsible for any in-patient phase its patients had. Cost was less. DLP care did not reduce the number of admissions, nor of deaths from self-harm (3 DLP, 2 control). One DLP patient killed a child. Even at 20 months many DLP and control patients still had severe symptoms, poor social adjustment, no job, and need for assertive follow-up and heavy staff input. (Beyond 20 months most gains were lost apart from satisfaction.)\n It is unclear how much the gain until 20 months from home-based care was due to its site of care, its being problem-centred, its teaching of daily living skills, its assertive follow-up, the home care team's keeping responsibility for any in-patient phase, its coordination of total care (case management), or to other care components. Home-based care is hard to organise and vulnerable to many factors, and needs careful training and clinical audit if gains are to be sustained.", "To evaluate the outcome and cost of transfer to a nursing-led inpatient unit for 'intermediate care'. The unit was designed to replace a period of care in acute hospital wards and promote recovery before discharge to the community.\n Randomized controlled trial comparing outcomes of care on a nursing-led inpatient unit with the system of consultant-managed care on a range of acute hospital wards.\n hospital wards in an acute inner-London National Health Service trust.\n 175 patients assessed to be medically stable but requiring further inpatient care, referred to the unit from acute wards.\n 89 patients were randomly allocated to care on the unit (nursing-led care with no routine medical intervention) and 86 to usual hospital care.\n Length of hospital stay, discharge destination, functional dependence (Barthel index) and direct healthcare costs.\n Care in the unit had no significant impact on discharge destination or dependence. Length of inpatient stay was significantly increased for the treatment group (P=0.036; 95% confidence interval 1.1-20.7 days). The daily cost of care was lower on the unit, but the mean total cost was pound sterlings 1044 higher-although the difference from the control was not significant (P=0.150; 95% confidence interval - pound sterlings 382 to pound sterlings 2471).\n The nursing-led inpatient unit led to longer hospital stays. Since length of stay is the main driver of costs, this model of care-at least as implemented here-may be more costly. However, since the unit may substitute for both secondary and primary care, longer-term follow-up is needed to determine whether patients are better prepared for discharge under this model of care, resulting in reduced primary-care costs." ]	Current research does not provide supporting evidence for a reduction in access to hospital services or a reduction in hospital readmission rate for children with acute and chronic illnesses using specialist home-based nursing services; however, the only summary finding across a few studies was that there is a significant decrease in length of hospitalisation. The preliminary results show no adverse impact on physical health outcomes and a number of papers reported improved satisfaction with home-based care. Further trials are required, measuring health, satisfaction, service utilisation and long-term costs.
CD001519	[ "8797480" ]	[ "Double-blind comparison of cabergoline and bromocriptine in Parkinson's disease patients with motor fluctuations." ]	[ "In the present study we compared the efficacy and safety of the new dopamine agonist cabergoline (CBG) with bromocriptine (BCR) in Parkinson's disease (PD). CBG has a very long half-life and can be administered as a single daily dose. Forty-four PD patients with uncontrolled motor fluctuations participated in the study. Patients were randomly and blindly assigned to equivalent doses of either CBG or BCR in addition to preexisting levodopa. Dosage was titrated to optimal, using up to 6 mg of CBG or 40 mg of BCR daily. CBG was given as a single morning dose whereas BCR was administered tid. Sixteen patients were followed for 1 year and 16 additional patients for 6 months. The mean follow-up duration was 9 +/- 5 months. The main effect of both drugs was observed on motor UPDRS scores, rigidity, bradykinesia items, and the percentage of awake hours spent during \"on\" and \"off\". In general, the effect of CBG was similar to that of BCR. The percentage of awake hours spent during \"on\" was higher with CBG as compared with BCR. Adverse events included dyskinesias, orthostatism, confusion, edema, and paresthesias in limbs. These effects were seen at similar frequencies with both drugs. The study shows that CBG given as a single morning dose is at least as efficacious as BCR given tid. CBG is a promising dopamine agonist for the treatment of motor fluctuations in PD." ]	Cabergoline produces similar benefits to bromocriptine in off time reduction, motor impairment and disability ratings, and levodopa dose reduction over the first three months of therapy. Dyskinesia and confusion were increased with cabergoline but otherwise the frequency of adverse events and withdrawals from treatment were similar with the two agonists.
CD002955	[ "2044398", "10945510", "11881837", "3301493", "3212603", "2285001", "321508" ]	[ "Efficacy of naftidrofuryl in patients with moderate senile dementia.", "Efficacy of naftidrofuryl in patients with vascular or mixed dementia: results of a multicenter, double-blind trial.", "Naftidrofuryl in the treatment of vascular dementia.", "[Efficacy and tolerance of long-term naftidrofuryl treatment of patients with senile dementia. Controlled study versus placebo].", "[Naftidrofuryl in patients with multi-infarct dementia and Alzheimer's disease].", "A randomized double-blind controlled trial of naftidrofuryl in acute stroke.", "A memory assessment technique for use in geriatric psychopharmacology: drug efficacy trial with naftidrofuryl." ]	[ "In a controlled double-blind study, 78 patients with moderate senile dementia were randomly assigned to 3-months' treatment with 200 mg naftidrofuryl twice daily in slow-release form or with placebo. The patients were selected on the basis of the EACG (Echelle d'Appréciation Clinique en Gériatrie), which was also used as main criterion for confirmatory analysis of the efficacy of naftidrofuryl. A further main criterion was the SGRS (Stockton Geriatric Rating Scale). Secondary criteria examined were visual memory as tested in the Benton test, verbal memory as tested in the Rey test and numerical memory as tested in the digit-span test. The patients' concentration was tested in the Zazzo test. The tests were performed before the patients were admitted to the study and after 1 and 3-months' treatment. Confirmatory analysis of the primary criteria showed a significant treatment difference in favour of naftidrofuryl in the form of improvement in the global symptoms of senile dementia both in the EACG and in the SGRS, the scores in the naftidrofuryl group improving by 15% compared with only 5% in the placebo group. This was paralleled by a significant improvement in visual and verbal memory in the naftidrofuryl group in comparison with placebo. The naftidrofuryl patients also showed a greater improvement in concentration than the placebo group. One patient in the naftidrofuryl group suffered briefly from gastro-intestinal symptoms. There were no changes in routine laboratory parameters studied.", "Dementia is a cerebral disorder resulting in a progressive deterioration of intellectual function that compromises the patient's ability to function. The diagnostic criteria for dementia are primarily clinical and are based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The Hachinski score and computed tomography of the brain help distinguish between degenerative and vascular dementias.\n This study examined the efficacy of naftidrofuryl in patients with vascular or mixed dementia.\n This multicenter, randomized, double-blind study compared naftidrofuryl 600 mg/d with placebo for 1 year in patients with vascular or mixed dementia. A preliminary 2-month washout period allowed selection of patients who were compliant with treatment. The end point was change in the scores on the Alzheimer Disease Assessment Scale cognitive subscale and the Mini-Mental State Examination.\n Eighty-four patients were assessable on an intent-to-treat basis, and 74 were assessable for the per-protocol analysis (on-treatment). Statistically significant improvements in cognitive and global function were observed in patients receiving naftidrofuryl. Naftidrofuryl was well tolerated, and produced no clinically significant abnormalities in laboratory test results.\n The results of this study suggest that naftidrofuryl is effective and well tolerated in treating the symptoms of vascular and mixed dementia.", "The design of this study was based on the European guidelines for the treatment of Alzheimer's disease. After a placebo run-in period of 4 weeks, patients with a diagnosis of vascular dementia (VaD) were randomised to receive either 400 mg naftidrofuryl/day, 600 mg naftidrofuryl/day or placebo for 6 months. The patients were assessed using the ADAS-cog, the SCAG, the NOSGER and the CGI item 2 scale. The primary analysis was undertaken on the ITT population. At the end of the study, significantly more patients in the treatment groups showed no deterioration on both ADAS-cog and SCAG scales compared with placebo (400 mg p = 0.005, 600mg p = 0.015). There were also significant differences between the active and placebo groups for the individual scales. This study has demonstrated that treatment with naftidrofuryl can slow the rate of deterioration of patients with vascular dementia.", "nan", "nan", "There is evidence to support the use of naftidrofuryl in acute stroke with claims of increased recovery, reduced fatality and reduced bed occupancy in patients treated with either oral or intravenous preparations. One hundred patients presenting with acute hemisphere stroke (less than 72 hours) were randomized to receive either a new oral formulation of naftidrofuryl or placebo on a double-blind basis. Treatment was given for a total of 12 weeks and patients followed for 26 weeks with serial neurological and functional assessments by a single observer. Cumulative fatality and hospital-bed occupancy were determined at each assessment interval. No significant difference was demonstrated in cumulative fatality, hospital-bed occupancy or recovery of motor function in patients treated with either naftidrofuryl or placebo. There is no evidence from this study to support the use of oral naftidrofuryl in acute stroke.", "This study was conducted to compare an automated test of paced stimulus material (Sperling's Perceptual Trace, SPT) with several other standard memory scales. Sixty patients with mild senile organic brain syndrome were divided into two groups of 30; one group was treated for 90 days with 300 mg daily of naftidrofuryl (Praxilene), and the other group received placebo. The patients were tested before treatment and at 30, 60 and 90 days after the beginning of treatment. The data indicated that the SPT indirectly assesses short-term memory, is resistant to practice effects, and is drug-sensitive. It is suggested that the SPT might become the test of choice in the indirect assessment of short-term memory in the elderly." ]	Oral administration of naftidrofuryl is well-tolerated by patients with dementia.The low-quality evidence shows that, by use of naftidrofuryl, people with dementia may benefit on performance, behaviour, cognition, and mood. However, the benefit on global impression is inconsistent and unconvincing.
CD003493	[ "9396958", "10360138", "11561046", "11313095", "15123391", "14960293", "19460131", "10197825", "9121622", "10686268", "11082469", "10622338", "10067953", "16955313" ]	[ "Mood improvement following daily left prefrontal repetitive transcranial magnetic stimulation in patients with depression: a placebo-controlled crossover trial.", "Double-blind controlled investigation of transcranial magnetic stimulation for the treatment of resistant major depression.", "Prefrontal repetitive transcranial magnetic stimulation as add on treatment in depression.", "Modest adjunctive benefit with transcranial magnetic stimulation in medication-resistant depression.", "Repetitive transcranial magnetic stimulation: a putative add-on treatment for major depression in elderly patients.", "Repetitive transcranial magnetic stimulation as treatment of poststroke depression: a preliminary study.", "Low-frequency transcranial magnetic stimulation in patients with fibromyalgia and major depression.", "Therapeutic efficacy of right prefrontal slow repetitive transcranial magnetic stimulation in major depression: a double-blind controlled study.", "Transcranial magnetic stimulation: a novel antidepressive strategy?", "A randomized clinical trial of repetitive transcranial magnetic stimulation in the treatment of major depression.", "A controlled trial of daily left prefrontal cortex TMS for treating depression.", "Repetitive transcranial magnetic stimulation (rTMS) in pharmacotherapy-refractory major depression: comparative study of fast, slow and sham rTMS.", "Repetitive transcranial magnetic stimulation in the treatment of medication-resistant depression: preliminary data.", "[Central and peripheral deafferent pain: therapy with repetitive transcranial magnetic stimulation]." ]	[ "Preliminary studies have indicated that daily left prefrontal repetitive transcranial magnetic stimulation might have antidepressant activity. The authors sought to confirm this finding by using a double-blind crossover design.\n Twelve depressed adults received in random order 2 weeks of active treatment (repetitive transcranial magnetic stimulation, 20 Hz at 80% motor threshold) and 2 weeks of sham treatment.\n Changes from the relevant phase baseline in scores on the 21-item Hamilton depression scale showed that repetitive transcranial magnetic stimulation significantly improved mood over sham treatment. During the active-treatment phase, Hamilton depression scale scores decreased 5 points, while during sham treatment the scores increased or worsened by 3 points. No adverse effects were noted.\n These placebo-controlled results suggest that daily left prefrontal repetitive transcranial magnetic stimulation has antidepressant activity when administered at these parameters. Further controlled studies are indicated to explore optimal stimulation characteristics and location, potential clinical applications, and possible mechanisms of action.", "The efficacy and safety of left prefrontal repetitive transcranial magnetic stimulation (rTMS) for treating resistant major depression were examined in a double-blind, controlled study.\n Eighteen medication-resistant depressed subjects were randomly assigned to 2 weeks of real or sham rTMS, then permitted up to 4 weeks of real rTMS. Effects on mood, neuropsychological function, EEG, and hearing were assessed.\n The groups receiving real and sham rTMS improved in mood significantly over the 2-week double-blind period, but there was no significant difference between groups.\n Repetitive transcranial magnetic stimulation did not provide significantly greater improvement than did sham treatment. A 4-week course of rTMS, as administered in this study, was safe.", "A growing number of studies report antidepressant effects of repetitive transcranial magnetic stimulation (rTMS) in patients with major depression. The hypothesis that high frequency (20 Hz) rTMS (HF-rTMS) may speed up and strengthen the therapeutic response to sertraline in MD was tested. Twenty eight patients who had not yet received medication for the present depressive episode (n=12) or had failed a single trial of an antidepressant medication (n=16) were started on sertraline and randomised to receive either real of sham HF-rTMS. HF-rTMS was applied to the left dorsolateral prefrontal area in daily sessions (30 trains of 2 s, 20-40 s intertrain interval, at 90% motor threshold) on 10 consecutive working days. The results suggest that in this patient population, HF-rTMS does not add efficacy over the use of standard antidepressant medication.", "Controverted results have been obtained using high frequency transcranial magnetic stimulation (HF-rTMS) as an antidepressant treatment.\n Forty patients suffering from drug-resistant major depression received ten sessions of HF-rTMS at 90% of the motor threshold on the left prefrontal cortex or sham stimulation, added to their pharmacological treatment, in a randomized double-blind design. In a second open phase, patients still fulfilling criteria of inclusion received ten additional sessions of HF-rTMS at 90 or 110%.\n Real, but not sham HF-rTMS, was associated with a significant decrease in the Hamilton Depression Rating Scale, but only twelve patients decreased more than 50%. Conclusions: Left prefrontal HF-rTMS was effectively associated with antidepressant treatment, although the size effect was small.\n Shortage of the sample and control difficulties of the placebo effect.\n Questionable in more than half of the patients studied.", "Repetitive transcranial magnetic stimulation (rTMS) is a recent putative treatment for affective disorders. Several studies have demonstrated antidepressant effects of rTMS in younger patients; we aimed to assess its effect in older outpatients with treatment-resistant major depression. Twenty-four outpatients (mean age=62 years, S.D.=12) with major depression were randomized for sham or real stimulation and received 10 daily rTMS sessions (20 Hz, 2-s trains, 28-s intertrain intervals, 100% of motor threshold) in addition to the antidepressant medication. For sham stimulation, the coil was tilted 90 degrees. Depression severity was assessed using the Hamilton Depression Rating Scale, the Beck Depression Inventory, items from the NIMH self-rated symptom scale, and a visual analog depression scale. Mini-Mental Status Examination performance, memory, and executive and attentional functions were measured to control for cognitive side effects. Depression ratings revealed significant antidepressant effects within 2 weeks in both sham and real stimulation groups; however, there were no between-group differences. Treatment with rTMS was safe; adverse events were rare and not more prevalent in either group, and cognitive assessment did not show any deterioration. We were unable to demonstrate any additional antidepressant effects of real stimulation in elderly patients with treatment-resistant major depression. Therapeutic effects of rTMS in this clinically challenging patient group remain to be demonstrated.", "Depression has a significant impact on poststroke recovery and mortality. There are a proportion of patients with poststroke depression (PSD) who do not respond to antidepressants. Repetitive Transcranial Magnetic Stimulation (rTMS) might be a safe and effective alternative in these refractory cases.\n We conducted a randomized, parallel, double-blind study of active versus sham left prefrontal rTMS in patients with refractory PSD. After discontinuing antidepressants, patients were randomly assigned to receive 10 sessions of active (10 Hz, 110% of the motor threshold, 20 trains of 5 seconds duration) or sham left prefrontal rTMS. Efficacy measures included HAM-D scores, response and remission rates. Patients completed a neuropsychological battery at baseline and after completing the protocol.\n When compared with sham stimulation, 10 sessions of active rTMS of the left dorsolateral prefrontal cortex were associated with a significant reduction of depressive symptoms. This reduction was not influenced by patient's age, type or location of stroke, volume of left frontal leukoaraiosis or by the distance of the stimulating coil to the prefrontal cortex. However, there was a significant positive correlation between the percentage of reduction of Ham-D scores and frontal gray and white matter volumes. There were no significant changes in cognitive functioning between the active and the sham stimulation groups. In addition, there were few and mild adverse effects that were equally distributed among groups.\n Taken together, these preliminary findings suggest that rTMS may be an effective and safe treatment alternative for patients with refractory depression and stroke.", "To study the efficacy of low-frequency transcranial magnetic stimulation in patients with fibromyalgia and major depression.\n Twenty-eight patients were randomly assigned to receive 20 sessions of real or sham transcranial magnetic stimulation of the right dorsolateral prefrontal cortex. The main stimulation parameters were 15 trains at 110% of the motor threshold for 60 seconds at a frequency of 1 Hz. Blinded external evaluators administered the fibromyalgia scales (FibroFatigue, Likert pain) and the depression scales (Hamilton Depression Rating Scale, Clinical Global Impression) during the study.\n Both treatment groups (real and sham) improved their scores in some of the scales (FibroFatigue and Clinical Global Impression), although there were no differences between them. No improvements were observed in the Likert Pain Scale in either of the groups.\n With the methodology used in this study, patients with fibromyalgia and major depression who received real magnetic stimulation did not present significant differences in symptoms with respect to those who received sham magnetic stimulation.", "Transcranial magnetic stimulation (TMS), a noninvasive technique for stimulation of the brain, has recently been suggested to be effective for the treatment of major depression. We conducted a double-blind, placebo-controlled study to assess the efficacy of slow repetitive TMS (rTMS) in patients with major depression.\n Seventy patients with major depression (53 women, 17 men; mean age, 58.7 years; SD, 17.2 years) were randomly assigned to receive rTMS or sham rTMS in a double-blind design. Treatment was administered in 10 daily sessions during a 2-week period. Severity of depression was blindly assessed before, during, and after completion of the treatment protocol.\n All patients completed the first week of treatment and 67 completed the entire protocol. Patients who received rTMS had a significantly greater improvement in depression scores compared with those who received sham treatment. At the end of 2 weeks, 17 of 35 patients in the rTMS group, but only 8 of 32 in the sham-treated group, had an improvement of greater than 50% in their depression ratings.\n This controlled study provides evidence for the short-term efficacy of slow rTMS in patients with recurrent major depression. Additional studies will be necessary to assess the efficacy of rTMS as compared with electroconvulsive therapy as well as the long-term outcome of this treatment in major depression and possibly other psychiatric disorders.", "Transcranial magnetic stimulation (TMS) is a well-established diagnostic probe in neurological practice. The increasing knowledge of biological mechanisms in electroconvulsive therapy presents a clear case for studying the applicability of TMS as a therapeutic tool in psychiatry. Based on the results of our pilot study showing a possible antidepressive effect of TMS, we conducted a controlled clinical trial on patients affected by major depression (DSM-III-R). Group 1 (n = 12) underwent TMS as add-on therapy to standard antidepressive medication, while group 2 (n = 12) was treated only with antidepressive medication. Already after the third add-on TMS session, a statistically significantly greater remission of depressive symptoms occurred in the patients of group 1 (p = 0.003). This statistically significant difference between the groups became even more marked on the last day of the study (p = 0.001, Wilcoxon). The results and further implications of TMS in psychiatric disorders are discussed.", "Multiple groups have reported on the use of repetitive transcranial magnetic stimulation (rTMS) in treatment-resistant major depression. The purpose of this study is to assess the efficacy of rTMS in unmedicated, treatment-resistant patients who meet criteria for major depression.\n Depressed subjects, who had failed to respond to a median of four treatment trials, were assigned in a randomized double-blind manner to receive either active (n = 10; 20 2-sec trains of 20 Hz stimulation with 58-sec intervals; delivered at 80% motor threshold with the figure-of-eight coil positioned over the left dorsolateral prefrontal cortex) or sham (n = 10; similar conditions with the coil elevated and angled 45 degrees tangentially to the scalp) rTMS. These sequences were applied during 10 consecutive weekdays. Continuous electroencephalogram sampling and daily motor threshold determinations were also obtained.\n The group mean 25-item Hamilton Depression Rating Scale (HDRS) score was 37.2 (+/- 2.0 SEM) points. Adjusted mean decreases in HDRS scores were 14.0 (+/- 3.7) and 0.2 (+/- 4.1) points for the active and control groups, respectively (p <.05). One of 10 subjects receiving active treatment demonstrated a robust response (i.e., HDRS decreased from 47 to 7 points); three other patients demonstrated 40-45% decreases in HDRS scores. No patients receiving sham treatment demonstrated partial or full responses.\n A 2-week course of active rTMS resulted in statistically significant but clinically modest reductions of depressive symptoms, as compared to sham rTMS in a population characterized by treatment resistance.", "Transcranial magnetic stimulation (TMS) is a new technology for noninvasively stimulating the brain. Several studies have suggested that daily stimulation of the left prefrontal cortex with TMS for 2 weeks has probable antidepressant effects. We conducted a parallel-design, double-masked, sham-controlled study to address whether 2 weeks of daily TMS over the left prefrontal cortex has antidepressant activity greater than sham.\n Thirty medication-free adult outpatients with nonpsychotic, major depressive (n = 21) or bipolar (n = 9) (depressed phase) disorder who were in a current major depression (Hamilton Rating Scale for Depression [HRSD] 21-item score of >18) were treated each weekday for 2 weeks. Subjects were randomly assigned to receive either daily active (20 subjects) or sham (10 subjects) stimulation. Additionally, the 20 active subjects were equally divided between slower (5 Hz) and faster (20 Hz) frequency treatment. Antidepressant response was defined as greater than a 50% improvement in the baseline HRSD.\n Active TMS resulted in significantly more responders (9/20) than did sham (0/10) (chi(2) = 6.42, p <.01). The number of responders did not differ significantly between the two active cells (3/10 faster and 6/10 slower). Expressed as a percent change from baseline, active TMS subjects had significantly greater improvement on the Beck Depression Inventory as well as the Hamilton Anxiety Rating Scale than did those who received sham.\n Daily left prefrontal TMS for 2 weeks significantly reduced depression symptoms greater than did sham. The two forms of active TMS treatment did not differ significantly.", "In previous studies, fast repetitive transcranial magnetic stimulation (rTMS) with a frequency > 1 Hz demonstrated substantial antidepressant effects compared to sham rTMS. However, it is not clear whether fast rTMS is superior to slow rTMS (frequency < or = 1 Hz) which is safe at therapeutically promising higher intensities. The aim of this double-blind study was to compare the action of fast, slow and sham rTMS. Eighteen patients with pharmacotherapy-resistant major depression were randomized to receive fast (10 Hz), slow (0.3 Hz) or sham rTMS with 250 stimuli/day for 5 successive days. rTMS was applied at 90% motor threshold intensity to the left dorsolateral prefrontal cortex. Scores on the Hamilton Depression Rating Scale (HDRS), but not on the Montgomery-Asberg Depression Rating Scale (MADRS), showed a statistically significant time x group interaction with a reduction of 19% after slow rTMS. However, the effect was clinically marginal and not reflected by self-rating scores. Verbal memory and reaction performance were not impaired after rTMS, and there was even a statistically significant time x group interaction with improvement of verbal memory performance after fast rTMS. In conclusion, this study further supported the safety of rTMS but does not show any clinically meaningful antidepressant efficacy of rTMS at 250 daily stimuli over 5 days in pharmacotherapy-refractory major depression.", "nan", "This study evaluates the effects of repeated sessions of low- and high-frequency repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex on central and phantom limb pain.\n Twenty seven patients with central (n=13) and phantom limb (n=14) pain participated in a blind, randomised placebo-controlled study comparing the effect of 1-Hz and 5-Hz rTMS with sham stimulation. Each treatment block consisted of a 5-day baseline phase, a 5-day therapy phase, and an 18-day washout phase. In the therapy phase, 500 stimuli were applied in the particular frequency at about the same time on each day.\n A reduction in pain immediately after stimulation was observed in all therapy groups. This effect was similar for all treatment conditions, including sham stimulation. No significant long-term effects of rTMS on pain intensity or mood were observed.\n At present, rTMS can not be recommended as a standard therapy for central and phantom limb pain." ]	The information in this review suggests that there is no strong evidence for benefit from using transcranial magnetic stimulation to treat depression, although the small sample sizes do not exclude the possibility of benefit.
CD005070	[ "20008886", "15979994", "15608037", "2970407", "18335226", "8974615", "15705367", "18192671", "19225876", "10519608" ]	[ "Flexible GnRH antagonist protocol versus GnRH agonist long protocol in patients with polycystic ovary syndrome treated for IVF: a prospective randomised controlled trial (RCT).", "A lower ongoing pregnancy rate can be expected when GnRH agonist is used for triggering final oocyte maturation instead of HCG in patients undergoing IVF with GnRH antagonists.", "GnRH antagonist versus long GnRH agonist protocol in poor responders undergoing IVF: a randomized controlled trial.", "Comparison between flare up and down regulation effects of luteinizing hormone-releasing hormone agonists in an in vitro fertilization program.", "Comparison of multiple dose GnRH antagonist and minidose long agonist protocols in poor responders undergoing in vitro fertilization: a randomized controlled trial.", "[Can the type of GnRH used during long in vitro fertilization protocols influence the pregnancy rate?].", "Evaluation of two doses of recombinant luteinizing hormone supplementation in an unselected group of women undergoing follicular stimulation for in vitro fertilization.", "GnRH agonist protocol administration in the luteal phase in ICSI-ET cycles stimulated with the long GnRH agonist protocol: a randomized, controlled double blind study.", "IVF/ICSI outcomes between cycles with luteal estradiol (E2) pre-treatment before GnRH antagonist protocol and standard long GnRH agonist protocol: a prospective and randomized study.", "Cessation of gonadotropin-releasing hormone analogue (GnRH-a) upon down-regulation versus conventional long GnRH-a protocol in poor responders undergoing in vitro fertilization." ]	[ "Women with polycystic ovary syndrome (PCOS) are at risk of developing ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation. Use of GnRH antagonist in the general subfertile population is associated with lower incidence of OHSS than agonists and similar probability of live birth but it is unclear if this is true for patients with PCOS. Our aim was to compare the flexible GnRH antagonist and GnRH agonist long protocols in patients with PCOS undergoing IVF (primary end-point: ongoing pregnancy rate per patient randomized).\n In this randomised controlled trial (RCT), 220 patients with PCOS were randomly allocated in two groups: long GnRH agonist down-regulation protocol (n = 110) and flexible GnRH antagonist protocol (n = 110).\n No differences were observed in ongoing pregnancy rates [50.9 versus 47.3%, difference 3.6%, 95% confidence interval (CI): -9.6 to +16.8%] in the agonist and antagonist protocols, respectively. Incidence of OHSS Grade II was lower in the antagonist compared with agonist group (40.0 versus 60.0%, difference -20.0%, 95% CI: -7.1 to -32.9%, P < 0.01). Duration of stimulation (10 versus 12 days, difference 2 days, 95% CI: +1 to +2, P < 0.001) and total gonadotrophin required (1575 versus 1850 IU, difference -275 IU, 95% CI: -25 to -400, P < 0.05) were also lower in the antagonist compared with agonist protocol.\n The current RCT suggests that the flexible GnRH antagonist protocol is associated with a similar ongoing pregnancy rate, lower incidence of OHSS grade II, lower gonadotrophin requirement and shorter duration of stimulation, compared with GnRH agonist. The GnRH antagonist might be the treatment choice for patients with PCOS undergoing IVF. The study was registered at clinicaltrials.gov. ID: NCT00417144.", "Eliciting an endogenous LH surge by GnRH-agonist for the induction of final oocyte maturation may be more physiological compared with the administration of HCG. However, the efficacy of this intervention in patients treated for IVF with GnRH antagonists remains to be assessed.\n 106 patients were randomized to receive either 10 000 IU urinary HCG or 0.2 mg Triptorelin for triggering final oocyte maturation. Ovarian stimulation for IVF was performed with a fixed dose of 200 IU recombinant FSH and GnRH antagonist was started on stimulation day 6. Luteal phase was supported with micronized vaginal progesterone and oral estradiol. The study was monitored continuously for safety and stopping rules were established.\n No significant differences were present in the number of cumulus-oocyte complexes retrieved, in the proportion of metaphase II oocytes, in fertilization rates or in the number and quality of the embryos transferred between the two groups. However, a significantly lower probability of ongoing pregnancy in the GnRH agonist arm prompted discontinuation of the trial, according to the stopping rules established (odds ratio 0.11; 95% confidence interval 0.02-0.52).\n Lower probability of ongoing pregnancy can be expected when GnRH agonist is used for triggering final oocyte maturation instead of HCG in patients undergoing ovarian stimulation for IVF with GnRH antagonists.", "This is the first published report of a prospective, randomized, controlled trial comparing a fixed, multi-dose GnRH antagonist protocol with a long GnRH agonist protocol in poor responders undergoing IVF.\n Sixty-six poor responders were randomized into two groups: the study group received 0.25 mg of cetrorelix daily starting on day 6 of stimulation; the control group received 600 microg of buserelin acetate daily starting in the mid-luteal phase of the preceding cycle. Both groups were given a fixed dose of recombinant FSH (300 IU daily) for stimulation.\n There were no significant differences in the cycle cancellation rates, duration of stimulation, consumption of gonadotrophins, and mean numbers of mature follicles, oocytes and embryos obtained. The implantation rates were similar, but the number of embryos transferred was significantly higher for the antagonist group (2.32 +/- 0.58 versus 1.50 +/- 0.83; P = 0.01). The pregnancy rates were also higher in the antagonist group, but the difference was not statistically significant.\n A fixed multi-dose GnRH antagonist protocol is feasible for patients who are poor responders on a long agonist protocol; however, our study failed to demonstrate an overall improvement in ovarian responsiveness. Clinical outcomes may be improved by developing more flexible antagonist regimens, an approach that requires further evaluation.", "Luteinizing hormone-releasing hormone (LH-RH) agonists are being increasingly used in ovulation stimulation protocols in IVF programs. The results of two methods of utilization of LH-RH agonists are compared. In the long protocol, gonadotropin stimulation was commenced only after a preliminary period of pituitary desensitization with LH-RH agonist. In the short protocol, exogenous gonadotropins were administered shortly after the start of LH-RH agonist therapy, benefiting from the gonadotropin flare up effect. One hundred eighty-six patients were equally divided between the two treatments. There was no difference in the ovarian response on the day of human chorionic gonadotropin (hCG) or the number of mature oocytes recovered. The cleavage rate of mature oocytes was higher in the short protocol (70% versus 56% P less than 0.01). The ongoing pregnancy rate per treatment cycle was similar in both groups (18% in the long protocol and 16% in the short protocol). Analysis of the luteal phases revealed a trend for higher progesterone values in the long protocol although this was only significant on the 2nd day following oocyte retrieval. As the clinical results were similar, other factors should be taken into account when deciding therapy. These include patient convenience, cost, and side effects. Other schedules of ovulation stimulation with LH-RH agonists are discussed.", "To investigate the efficacy of gonadotropin releasing hormone antagonist (GnRH) in poor responders undergoing in vitro fertilization.\n Ninety-six patients with poor ovarian response in previous treatment cycles were prospectively randomized into two groups. Forty-four patients were stimulated with GnRH antagonist multidose protocol and 45 patients received a standard long agonist protocol. Ovarian response was evaluated by transvaginal ultrasound and hormonal parameters. Cycle characteristics and treatment outcomes were statistically compared between groups.\n There was significantly reduced duration of stimulation and consumption of gonadotrophins in the antagonist group when compared to the agonist group. The estradiol concentrations on the day of human chorionic gonadotropin (hCG) injection, the number of oocytes retrieved, and the number of embryos transferred were similar for both groups. In the antagonist group, eight (18.1%) ongoing pregnancies were achieved and in the agonist group, ten (22.2%) clinical pregnancies were achieved but the difference was not statistically significant.\n The present study was not powered to detect clinically relevant differences between two protocols in outcomes such as pregnancy rate, with confidence.", "Luteal defect is common during IVF cycles using GnRH agonist. It could be interesting to make up for this problem by using short acting GnRH agonist (effective for 24 hours), more handy at the end of the stimulation. 160 patients included in a long IVF protocol at the Bordeaux CHRU FIV center have been randomized, from September 1993 to August 1994, for the analog's choice (long or short) at the beginning of the stimulation. The stimulation's parameters, the hormonal dosages and the pregnancy rate are independent of the galenic form used. In close, the use of long-acting GnRH analog (sympler to use) sems preferable.", "To evaluate the efficacy of two doses of recombinant (r)LH, 75 IU (recommended) or 37.5 IU, for follicular stimulation and outcomes in a randomized cohort of IVF patients.\n Randomized, prospective analysis.\n Private hospital incorporating an established IVF center.\n Women undergoing IVF who had a body mass index >18 or <35 and no abnormal karyotype, anovulation, oligomenorrhea, or any known endocrinopathy/illness.\n Pituitary desensitization was achieved with triptorelin (0.1 mg SC), and gonadotropin stimulation was performed with either rFSH alone (group A) or in combination with rLH in one of two doses: 37.5 IU (group B) or 75 IU (group C), daily.\n A range of endocrinologic, embryologic, clinical, and outcome parameters were evaluated.\n With rLH supplementation there was a significant increase in the incidence of implantation (9% for rFSH only [group A] vs. 11% and 16% with 37.5 IU rLH and 75.0 IU rLH [groups B and C], respectively) and clinical pregnancy (19% vs. 23% and 31%) (P<.01 and P<.04, respectively), whereas there was no difference in the multiple pregnancy rates. There was a significant (P<.001) increase in the total units of rFSH used in proportion to the amount of rLH supplementation (2,645 U vs. 3,475 U and 3,681 U) and in the level of peripheral E(2) on the day of hCG administration (1,049 pg/mL vs. 1,640 pg/mL and 1,226 pg/mL) (P<.001). There was no significant between difference in mean age, numbers of oocytes recovered, basal and downregulation hormone levels, or the incidence of fertilization in the absence or presence of rLH supplementation, but a higher incidence of grade 1 to 2 embryos was observed when rLH was supplemented.\n After pituitary desensitization, there was an increase in the incidence of implantation, clinical pregnancy, and delivery rates in patients stimulated with rFSH supplemented with rLH.", "GnRH agonist administration in the luteal phase was reported to beneficially affect the clinical outcome of intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) cycles. This double blind, randomized, placebo controlled trial evaluates whether a single dose GnRH agonist administered 6 days after ICSI increases ongoing pregnancy rates following ET in cycles stimulated with the long GnRH agonist protocol.\n Five hundred and seventy women undergoing ET following controlled ovarian stimulation with a long GnRH agonist protocol were included. In addition to routine luteal phase support with progesterone, women were randomized to receive a single 0.1 mg dose of triptorelin or placebo 6 days after ICSI. Randomization was done on the day of ET according to a computer generated randomization table. Ongoing pregnancy rate beyond 20th week of gestation was the primary outcome measure. The trial was powered to detect a 12% absolute increase from an assumed 38% ongoing pregnancy rate in the placebo group, with an alpha error level of 0.05 and a beta error level of 0.2.\n There were 89 (31.2%) ongoing pregnancies in the GnRH agonist group, and 84 (29.5%) in the control group (absolute difference +1.7%, 95% confidence interval -5.8% to +9.2%). Implantation, clinical pregnancy and multiple pregnancy rates were likewise similar in the GnRH agonist and placebo groups.\n Single 0.1 mg triptorelin administration 6 days after ICSI following ovarian stimulation with the long GnRH agonist protocol does not seem to result in an increase >or=12% in ongoing pregnancy rates.", "To study if luteal E(2) pre-treatment before GnRH antagonist protocol improves IVF/ICSI outcomes compared with standard long GnRH agonist protocol.\n A prospective, randomized and controlled study.\n ART center of a state public hospital\n Two hundred twenty infertile women underwent IVF/ICSI treatments.\n Participants received oral Estradiol Valerate 4 mg/day preceding the IVF cycle from day 21 until day 2 of next cycle before GnRH antagonist protocol (E(2) pre-treatment group n=109) or received standard long GnRH agonist protocol as control group (n=111).\n Number of oocytes collected, MII oocytes, fertilization, implantation, live birth and early pregnancy rate, and hormone profiles.\n E(2) pre-treatment exerted a significant suppressive effect on FSH but not LH secretion compared with basal FSH and LH levels. In E(2) pre-treatment group serum LH level was significantly higher during COH and serum P was also significantly higher on the day of HCG injection compared with control group. Five patients from E(2) pre-treatment group had elevated LH at all time (>or= 10 IU/L) and also a concomitantly high P (>1 ng/mL). Two of the five women achieved pregnancy but had early pregnancy loss. Overall, IVF/ICSI outcomes such as implantation, clinical pregnancy and live birth rates were similar between E(2) pre-treatment and control groups.\n Luteal E(2) pre-treatment before GnRH antagonist protocol significantly increases serum LH level and incidence rate of premature LH but no significant effect is observed on implantation, clinical pregnancy, live birth and early pregnancy loss rates compared with long GnRH agonist protocol. However, more studies in large numbers of cycles are needed to confirm that increased serum LH level by E(2) pre-treatment during COH has no negative effect on the IVF/ICSI outcomes.", "To determine whether a controlled ovarian hyperstimulation (COH) regimen that involves GnRH agonist (GnRH-a) discontinuation before administration of gonadotropins would benefit poor responders.\n A prospective, randomized controlled trial.\n Hospital-based IVF Unit.\n Sixty-three patients with previous poor response to COH and/or high basal FSH level (> or =9 mIU/mL) undergoing 78 IVF-ET cycles.\n In both groups, administration of GnRH-a was started in the midluteal phase. Whereas in the study group (40 cycles), it ended before administration of gonadotropins, in controls (38 cycles) GnRH-a treatment was continued throughout the follicular phase.\n Ovarian stimulation patterns and IVF outcome.\n A significantly higher cancellation rate was noted in the study group than in the controls (22.5% versus 5%, respectively). The new and control regimens resulted in similar stimulation characteristics and clinical pregnancy rates (11% versus 10.3%, respectively). In 13 patients with a basal FSH level that was not persistently high, the new regimen resulted in a significantly higher number of retrieved oocytes compared with the standard protocol (7.6+/-1.03 versus 4.0+/-0.68, respectively).\n Whereas for most low responders, the new COH regimen offers no further advantage, future prospective studies may demonstrate whether it can confer a benefit for a subset of patients with a basal FSH level that is not persistently high." ]	There was no evidence of a statistical difference in pregnancy outcomes when rLH was used. Nevertheless, further large RCTs should be undertaken in long GnRH agonist down regulation protocols, since all pooled pregnancy estimates, although not statistically different probably due to the small numbers, point towards a beneficial effect of co-treatment with rLH, in particular with respect to pregnancy-loss and poor-responders.
CD001398	[ "10325288", "1572493" ]	[ "Ablation of lesions or no treatment in minimal-mild endometriosis in infertile women: a randomized trial. Gruppo Italiano per lo Studio dell'Endometriosi.", "Fertility outcome after conservative surgical treatment of ectopic pregnancy evaluated in a randomized trial." ]	[ "In order to analyse the efficacy of resection/ablation of minimal/mild endometriotic lesions for improving fertility, we conducted a randomized clinical trial. Eligible patients were women aged </=36 years who were trying to conceive and had a laparoscopically confirmed diagnosis of minimal/mild endometriosis (stage I or II of the revised American Fertility Society classification) and otherwise unexplained infertility for >/=2 years. Eligible women were randomly assigned to resection or ablation of visible endometriosis (54 patients) or diagnostic laparoscopy only (47 patients). After laparoscopy women tried to conceive spontaneously for 1 year (follow-up period). A total of five women withdrew from the study: three for personal reasons, and two were lost to follow-up. Considering 51 women in the resection/ablation and 45 in the no-treatment group who ended the follow-up period, 12 (24%) in the resection/ablation group and 13 (29%) in the no treatment group conceived; the difference was not significant. Two spontaneous abortions were observed in the resection/ablation group and three in the no-treatment one. Thus the 1 year birth rate was 10 out of 51 women (19.6%) in the resection/ablation group and 10 out of 45 women (22.2%) in the no-treatment group. In conclusion, the results of this study do not support the hypothesis that ablation of endometriotic lesions markedly improves fertility rates.", "To evaluate the fertility outcome after laparoscopic surgery for ectopic pregnancy.\n A randomized trial versus laparotomy was performed between May 1987 and June 1989.\n The study was conducted in a clinical university center, the Sahlgrens Hospital.\n A group of 105 patients with tubal pregnancy were stratified with regard to risk determinants and age and randomized to laparoscopy or laparotomy. Eighty-seven patients who desired pregnancy were evaluated for subsequent fertility outcome.\n Linear salpingotomy was performed in both surgical groups.\n We evaluated the fertility outcome after laparoscopic salpingotomy for comparison with the outcome after laparotomy.\n There was no difference between the groups in the overall fertility outcome. A substantially higher proportion of patients in the laparotomy group were subjected to adhesiolysis performed at a second-look laparoscopy.\n The fertility prospects are not impaired by laparoscopic surgery. Adhesiolysis at a second-look laparoscopy, especially after laparotomy, might be beneficial in selected cases and may serve to improve subsequent fertility." ]	The use of laparoscopic surgery in the treatment of subfertility related to minimal and mild endometriosis may improve future fertility.
CD006267	[ "16633002", "8269230", "15570204", "11742165", "9172113", "11793255", "15791369", "16956334", "19943593" ]	[ "Safety, feasibility, and short-term outcomes of laparoscopic ileal-pouch-anal anastomosis: a single institutional case-matched experience.", "Laparoscopic assisted abdominoperineal resection.", "Hand-assisted laparoscopic versus open restorative proctocolectomy with ileal pouch anal anastomosis: a randomized trial.", "Functional outcome, quality of life, body image, and cosmesis in patients after laparoscopic-assisted and conventional restorative proctocolectomy: a comparative study.", "Laparoscopy. Gasless vs. CO2 pneumoperitoneum.", "A comparison between open versus laparoscopic assisted colonic pouches for rectal cancer.", "Laparoscopic-assisted approach in rectal cancer patients: lessons learned from >200 patients.", "Psychological wellbeing after laparoscopic and abdominal hysterectomy--a randomised controlled multicentre study.", "A quality of life comparison of laparoscopic and open approaches in acute appendicitis: a randomised prospective study." ]	[ "To compare safety and short-term outcomes of 100 laparoscopic ileal pouch-anal anastomosis (IPAA) versus 200 conventional open IPAA patients.\n Outcomes of laparoscopic IPAA (LAP-IPAA) have been incompletely characterized. Previous reports are characterized by small numbers of patients and rarely include case-matched or randomized trial methodology. This report describes 100 LAP-IPAA patients case matched to 200 open IPAA patients.\n Between 1998 and 2004, 100 consecutive LAP-IPAA patients (75 laparoscopic assisted, 25 hand assisted) were identified and case matched to 200 open IPAA control patients by age, operation, gender, date of operation, and body mass index. Operative and postoperative outcomes at 90 days were compared.\n A total of 300 patients (180 female) with a median age of 32 years (range, 17-66 years), and a median body mass index of 23 kg/m (range, 16-34 kg/m) underwent IPAA (100 LAP-IPAA, 200 open IPAA). Diagnosis (chronic ulcerative colitis 97%, familial adenomatous polyposis 3%) and previous operative history were equivalent between groups. One intraoperative complication occurred in each group. Overall, the laparoscopic conversion rate was 6%. Median operative time was longer for the LAP-IPAA group (333 minutes versus 230 minutes, P < 0.0001). LAP-IPAA patients had shorter median time to regular diet (3 versus 5 days), time to ileostomy output (2 versus 3 days), length of stay (4 versus 7 days), and decreased IV narcotic use (all P < 0.05. Postoperative morbidity was equivalent (LAP-IPAA = 33%, open IPAA = 37%), mortality was nil, and readmission rates were equal (LAP-IPAA = 21%, open IPAA = 22%). Reoperation was required in 3% of LAP-IPAA and 6.5% of open IPAA patients (P < 0.2) during the first 3 months.\n LAP-IPAA is equivalent to open IPAA in terms of safety and feasibility. In addition, LAP-IPAA provides significant improvements in short-term recovery outcomes.", "A technique is described for laparoscopic abdominoperineal resection (APR). Three of four such cases could be successfully completed laparoscopically. One major complication was directly related to the laparoscopic approach, an enterotomy caused by the Babcock clamp, which was discovered at the time of conversion to laparotomy for bleeding. A minor complication related to the laparoscopic procedure, subcutaneous emphysema, required no treatment. There was one postoperative death unrelated to the laparoscopic technique. The intraoperative advantage was enhanced visualization; the intraoperative disadvantages were increased operative time and cost. Postoperative advantages were earlier mobilization, oral intake, and discharge; decreased pain; and improved cosmesis. Laparoscopic APR is both feasible and safe and with more experience should prove to be cost effective.", "The aim of the study was to evaluate postoperative recovery after hand-assisted laparoscopic or open restorative proctocolectomy with ileal pouch anal anastomosis for ulcerative colitis and familial adenomatous polyposis in a randomized controlled trial.\n Sixty patients were randomized for hand-assisted laparoscopic (n = 30) or open surgery (n = 30). Primary outcome parameter was postoperative recovery in the 3 months after surgery, measured by quality of life questionnaires (SF-36 and GIQLI). Secondary parameters were postoperative morphine requirement and surgical parameters, viz. operating time, morbidity, hospital stay, and costs.\n There was no difference between the 2 procedures in quality of life assessment in the 3 months after surgery. There was a significant decline in quality of life on all scales of the SF-36 (P < 0.001) and total GIQLI score (P < 0.001) in the first 2 weeks in both groups (no significant difference between the groups). Quality of life returned to baseline levels after 4 weeks. Operating times were longer in the laparoscopic group compared with the open group (210 and 133 minutes, respectively; P < 0.001). No significant differences were found in morphine requirement. Neither morbidity nor postoperative hospital stay differed between the laparoscopic and open group (20% versus 17%, in 10 versus 11 days, respectively). Median overall costs were 16.728 for the hand-assisted laparoscopic procedure and 13.406 for the open procedure (P = 0.095).\n Recovery measured using quality of life questionnaires is comparable for hand-assisted laparoscopic or open restorative proctocolectomy with ileal pouch anal anastomosis. The laparoscopic approach is as safe, but more costly than the open procedure.", "The aim of this study was to assess the functional outcome and the quality of life of laparoscopic-assisted ileal pouch-anal anastomosis compared with conventional ileal pouch-anal anastomosis. Further, body image and cosmesis were evaluated in both groups.\n Sixteen patients who underwent a laparoscopic-assisted ileal pouch-anal anastomosis between March 1996 and September 1999 were matched with 19 patients who had a conventional ileal pouch-anal anastomosis. Patients were matched for the time period after surgery, distribution of familial adenomatous polyposis/ulcerative colitis, and one/two-stage procedure. Thirty-two patients agreed to fill out a set of questionnaires that assessed functional outcome, quality of life, body image, and cosmesis. Quality of life was measured with the Short Form 36 Health Survey questionnaire and the Gastrointestinal Quality of Life Index. The Body Image Questionnaire was used to measure patients' perceptions of and satisfaction with their own body and their attitude toward their bodily appearance (body image) and the degree of satisfaction of patients with respect to the physical appearance of the scar (cosmesis).\n Patients in the conventional group were older than patients in the laparoscopic-assisted group (mean 39.2 +/- 8.4 vs. 30.6 +/- 7.1 years; P < 0.01). No differences were found in functional outcome and quality of life. Satisfaction with the cosmetic result of the scar was significantly higher in the laparoscopic-assisted group compared with the conventional group. Body image score was higher in the laparoscopic-assisted group when compared with the conventional group, although not significant.\n The functional outcome and quality of life of laparoscopic-assisted ileal pouch-anal anastomosis is not different from conventional ileal pouch-anal anastomosis. In the long-term, better cosmesis is the most important advantage after laparoscopic surgery.", "To compare gasless laparoscopy with conventional laparoscopy using CO2 pneumoperitoneum.\n Women undergoing bilateral laparoscopic tubal coagulation (LTC) were randomly assigned to one of two laparoscopy procedures: (1) a gasless laparoscopy system consisting of an intraabdominal fan retractor and electrically powered mechanical arm, and (2) standard CO2 pneumoperitoneum laparoscopy. The two laparoscopic procedures were compared on the basis of intraoperative visualization, operation duration, procedural difficulty, ventilatory parameters, hemodynamic stability, and postoperative pain and nausea.\n Significant disadvantages for the surgeon (increased technical difficulty, poorer visualization, longer operative times) and patient (greater postoperative pain and nausea) were seen with the gasless system. Because of these findings, the study was prematurely terminated after only 18 patients had participated. Intraoperative ventilatory and hemodynamic parameters were more stable in the gasless laparoscopy groups; however, the differences were not clinically significant in this population of healthy patients.\n The markedly increased technical difficulty and absence of clear clinical benefits for the healthy patient led to the conclusion that laparoscopy with CO2 pneumoperitoneum is preferable for routine LTC and most laparoscopic procedures in the pelvis. Gasless laparoscopy may be of benefit for the fragile patient with a compromised cardiovascular system who may suffer complications from hypercarbenemia.", "The aim of this prospective study was to compare the surgical outcomes in patients undergoing laparoscopic assisted vs. open ultralow anterior resection (ULAR) with the creation of a colonic pouch-anal anastomosis. Patients undergoing ULAR with creation of a colonic pouch and who either had conventional open (CO) or laparoscopic assisted (LA) surgery in colorectal cancer were studied and compared. There were 33 patients, 22 in CO group and 11 in LA group. The groups were comparable for age, sex, tumour and anastomotic heights from anal verge, stage of disease, length of specimen removed and duration of surgery. Incisions were significantly shorter in the LA group (median, 9 cm vs. 16 cm, p = 0.01). Less parenteral analgesia was required in the LA group (2 days vs. 3 days, p = 0.05), but there were no significant differences in the time to passage of flatus, commencement of oral fluids or solid foods and length of hospital stay. There was no difference in morbidity or mortality. With regards to patients with Dukes A to C disease only, at a median of 12 months of follow-up, there was no patient with local or port site recurrence in the LA group. In the CO group, there was one local recurrence and two with distal metastases. In conclusion, laparoscopic assisted ULAR with colonic J pouch anal anastomosis is feasible, easy to perform and safe. It s advantages include significantly shorter incision and lower analgesic requirements postoperatively. Return of bowel function and length of hospital stay, however, are comparable to those of conventional open surgery.", "The applicability of laparoscopic surgery in the treatment of colorectal diseases is still controversial. Early reports on laparoscopic-assisted colectomy in patients with colon cancer suggested that it minimizes surgical trauma, decreases perioperative complications, and leads to a more rapid recovery. To our knowledge, no previous studies have compared the laparoscopic vs the open approach in rectal cancer. The aim of this paper was to assess the results of laparoscopic techniques in patients with rectal cancer.\n From March 1998 to February 2003, all patients admitted to our unit with adenocarcinoma of the rectum were evaluated for surgery by the laparoscopic approach.\n A total of 220 patients with a mean age of 67.3 years were included in the study. One hundred thirty patients (59%) were treated with neoadjuvant chemoradiotherapy. In >75% of the patients, a surgical procedure with sphincter preservation was performed. The rate of conversion to the open approach was 20%. Ten patients had intraoperative complications. Fifty-eight patients (26.3%) developed postoperative complications. The length of hospital stay was 6.8 days. The distribution of tumor stages was as follows: stage I, 16.81%; stage II, 33.6%; stage III, 26.36%; stage IV, 19.09%. The mean number of lymph nodes was 13.8. The incidence of local relapse was 5.3%, with a follow-up of 18 months.\n Laparoscopic surgery can be safely performed in patients with adenocarcinoma of the rectum with good short-term results. Randomized controlled trials are needed to confirm these results.", "To compare laparoscopic hysterectomy and abdominal total hysterectomy regarding influence on postoperative psychological wellbeing and surgical measures.\n A prospective, open, randomised multicentre trial.\n Five hospitals in the South East of Sweden.\n Hundred and twenty-five women scheduled for hysterectomy for benign conditions were enrolled in the study, and 119 women completed the study. Fifty-six women were randomised to abdominal hysterectomy and 63 to laparoscopic hysterectomy.\n Psychometric tests measuring general wellbeing, depression and anxiety preoperatively and 5 weeks and 6 months postoperatively.\n Effects of operating method on the psychological wellbeing postoperatively. Analysis of data regarding operating time, peroperative and postoperative complications, blood loss, hospital stay and recovery time.\n No significant differences in the scores were observed between the two groups in any of the four psychometric tests. Both the surgical methods were associated with a significantly higher degree of psychological wellbeing 5 weeks postoperatively compared with preoperatively. The operating time was significantly longer for the laparoscopic hysterectomy group, but the duration of the stay in hospital and sick-leave were significantly shorter for laparoscopic hysterectomy group compared with the abdominal hysterectomy group.\n General psychological wellbeing is equal after laparoscopic and abdominal hysterectomy within 6 months after the operation. The advantages of the laparoscopic hysterectomy are the shorter stay in hospital and shorter sick-leave, but these issues must be balanced by a longer duration of the operation.", "The study aimed to evaluate the utility of a laparoscopic approach in the management of patients with right lower abdominal pain and in the quality of life after the operation.\n Patients with suspected appendicitis were included in the study. They were randomly assigned either to treatment with a traditional open approach or with a laparoscopic approach. The patients' data, including demographic data, complications and gastro-intestinal quality of life index scores, were collected at the 6th week and 6th month and compared between the groups.\n Overall, 83 appendectomies were performed. Other pathologies were ovulation bleeding, ovarian cyst, Meckel's diverticulum, ectopic pregnancy and leiomyoma of the uterus. Negative appendectomy rate was 7%. Severe infection occurred in five of the open group. The advantages of the laparoscopy also showed significantly in hospital stay (55.80 +/- 20.97 hours vs. 75.06 +/- 35.14 hours), the need for narcotics and in visual analog score, as well as in the gastrointestinal quality of life index (85.88 +/- 9.73 vs 101.30 +/- 9.31). The quality of life is still better in the long-term (95.14 +/- 8.45 vs 120.36 +/- 10.25). When the groups were compared according to the subgroups of gastro-intestinal quality of life index, except for disease-specific items, in all categories a significant improvement was seen in the laparoscopically treated patients. This improvement was observed in the follow-up period also. However, the hospital costs (987.50 +/- 77.25 USD vs. 406.27 +/- 100.59 USD) and operative time (56.25 +/- 10.9 vs. 49.41 +/- 11.76 minutes) still continued to be a problem for the laparoscopic group.\n Laparoscopic appendectomy is a safe method, which also has advantages of diagnostic procedure for other pathologies, a better quality of life both in the early and late period, and a short hospital stay. The important advantage is also seen in the late period with better quality of life." ]	The laparoscopic IPAA is a feasible and safe procedure. Short-term advantages of the laparoscopic approach seem to be limited and their clinical significance is arguable. Large high-quality trials focusing on differences regarding specific postoperative complications, cosmesis, quality of life and costs are needed.
CD004515	[ "12410546" ]	[ "Effect of valepotriates (valerian extract) in generalized anxiety disorder: a randomized placebo-controlled pilot study." ]	[ "The aim of the present study was to carry out a controlled pilot study on the putative anxiolytic effect of valepotriates. Thirty-six outpatients with generalized anxiety disorder (DSM III-R), after a 2-week wash-out, were randomized to one of the following three treatments for 4 weeks (n = 12 per group): valepotriates (mean daily dose: 81.3 mg), diazepam (mean daily dose: 6.5 mg), or placebo. A parallel, double-blind, flexible-dose, placebo-controlled design was employed. No significant difference was observed among the three groups at baseline or in the change from baseline on the Hamilton anxiety scale (HAM-A) or in the trait part of the state-trait anxiety inventory (STAI-trait). Moreover, the three groups presented a significant reduction in the total HAM-A scores. On the other hand, only the diazepam and valepotriates groups showed a significant reduction in the psychic factor of HAM-A. The diazepam group also presented a significant reduction of the STAI-trait. Although the principal analysis (HAM-A between group comparison) found negative results (probably due to the small sample size in each group), the preliminary data obtained in the present study suggest that the valepotriates may have a potential anxiolytic effect on the psychic symptoms of anxiety. However, since the number of subjects per group was very small, the present results must be viewed as preliminary. Thus, further studies addressing this issue are warranted.\n Copyright 2002 John Wiley & Sons, Ltd." ]	Since only one small study is currently available, there is insufficient evidence to draw any conclusions about the efficacy or safety of valerian compared with placebo or diazepam for anxiety disorders. RCTs involving larger samples and comparing valerian with placebo or other interventions used to treat of anxiety disorders, such as antidepressants, are needed.
CD005131	[ "2181748", "11769665", "14716182", "1921739", "1641524", "10428529", "11755552", "1465038", "2089297" ]	[ "[Treatment with low-dose vaginal estradiol in post-menopausal women. A double-blind controlled trial].", "[Prevention and treatment of recurrent urinary system infection with estrogen cream in postmenopausal women].", "Efficacy of low-dose intravaginal estriol on urogenital aging in postmenopausal women.", "Efficacy of sustained-release vaginal oestriol in alleviating urogenital and systemic climacteric complaints.", "Oestriol in the prophylactic treatment of recurrent urinary tract infections in postmenopausal women.", "The effect of oestrogen supplementation on post-menopausal urinary stress incontinence: a double-blind placebo-controlled trial.", "Urinary tract infections in postmenopausal women: effect of hormone therapy and risk factors.", "Preoperative treatment with oestradiol in women scheduled for vaginal operation for genital prolapse. A randomised, double-blind trial.", "[Transvaginal estrogen therapy in urinary stress incontinence]." ]	[ "Twenty-three postmenopausal women with recurrent cystitis were allorted at random to treatment for five months with local oestrogen in the vagina or placebo treatment with the object of assessing the local effect on the vaginal epithelium and on the tendency to recurrent cystitis. The therapeutic group and the placebo group were entirely comparable prior to treatment. In the therapeutic group, the oestrogen index in vaginal scrapings was significantly higher after treatment than in the placebo group (p less than 0.01). The number of positive urine cultures and the patients/satisfaction with treatment wee not significantly different in the two groups.", "To evaluate the effect and feasibility of using estrogen cream for the prevention and treatment of recurrent urinary tract infection (UTI) in postmenopausal women.\n Forty-five postmenopausal women with a history of recurrent UTI were divided into two groups (group premarin and group antibiotic). Participants were assigned to apply intravaginal premarin cream (group premarin, n = 30) or oral antibiotic (group antibiotic, n = 15) for 3 months respectively. Urine routine test, midstream urine and vaginal cultures, vaginal health score (VHS), vaginal cell maturation value (MV), endometrial thickness and blood estrogen level were obtained before and after the study.\n The incidence of UTI in the group premarin was significantly reduced as compared with that in the group antibiotic (2/27 vs. 12/15, P < 0.001). In the group premarin Lactobacilli reappeared (from 0 to 59.3%) and MV (from 9.2 +/- 6.8 to 74.6 +/- 14.1) and VHS (from 5.2 +/- 0.4 to 13.4 +/- 2.5) were improved after 3 months. There was no significant change in the group antibiotic.\n It seems that intravaginal use of estrogen cream would effectively prevent and reduce the UTI in postmenopausal women.", "To assess the efficacy and safety of intravaginal estriol administration on urinary incontinence, urogenital atrophy, and recurrent urinary tract infections in postmenopausal women.\n Eighty-eight postmenopausal women with urogenital aging symptoms were enrolled in this prospective, randomized, placebo-controlled study. Participants were randomly divided into two groups, with each group consisting of 44 women. Women in the treatment group received intravaginal estriol ovules: 1 ovule (1 mg) once daily for 2 weeks and then 2 ovules once weekly for a total of 6 months as maintenance therapy. Women in the control group received inert placebo vaginal suppositories in a similar regimen. We evaluated urogenital symptomatology, urine cultures, colposcopic findings, urethral cytologic findings, urethral pressure profiles, and urethrocystometry before as well as after 6 months of treatment.\n After therapy, the symptoms and signs of urogenital atrophy significantly improved in the treatment group in comparison with the control group. Thirty (68%) of the treated participants, and only seven (16%) of the control participants registered a subjective improvement of their incontinence. In the treated participants, we observed significant improvements of colposcopic findings, and there were statistically significant increases in mean maximum urethral pressure, in mean urethral closure pressure as well as in the abdominal pressure transmission ratio to the proximal urethra. Urethrocystometry showed positive but not statistically significant modifications.\n Our results show that intravaginal administration of estriol may represent a satisfactory therapeutic choice for those postmenopausal women with urogenital tract disturbances who have contraindications or refuse to undergo standard hormone therapy.", "In a double-blind, placebo-controlled study, 109 patients suffering from local and vasomotor postmenopausal complaints were randomly assigned to treatment with either depot vaginal suppositories containing 3.5 mg oestriol (E3) or a placebo. The treatment schedule comprised one vaginal suppository twice weekly for 3 weeks initially, followed by maintenance therapy with one vaginal suppository weekly for the 6-month study period. The effectiveness of the therapy was assessed on the basis of questionnaires (Kupperman index for vasomotor complaints and an original urogenital index for local complaints) and gynaecological examinations which included assessments of vaginal cytology, vaginal pH and Döderlein bacilli. To rule out induced endometrial proliferation, endometrial biopsies were performed in 50 women before and after the study. The vaginal depot (E3) formulation showed highly significant superiority over the placebo with respect to therapeutic effect on local urogenital complaints and alleviation of vasomotor complaints, including hot flushes. Analysis of the endometrial biopsies indicated that the monotherapy used caused no endometrial stimulation. Taking into account the minimal rate of adverse effects, the 3.5 mg E3 depot formulation studied represents a useful variant in the range of preparations available for the treatment of post-menopausal complaints.", "A block randomized, double-blind, group-comparative, placebo-controlled study was conducted to assess the effect of oestriol on recurrent urinary tract infections in postmenopausal women. 40 women, median age 78 years (66-91), 20 in each group, were treated with oestriol three mg p.o. per day or corresponding placebo for four weeks, followed by one mg per day for eight weeks. The main response parameter was the number of urinary tract infections per week in the two treatment periods. Both oestriol and placebo reduced the number of infections per week significantly in both periods, compared with the pretreatment period. There was no difference between oestriol and placebo treatment in the first period. In the second period, however, oestriol treatment was significantly more effective than placebo (p = 0.05). Correspondingly, there was a significant difference between the two groups in the vaginal pH at the end of the study (p less than 0.05). We conclude that oestriol reduces recurrent urinary tract infections in postmenopausal women.", "To investigate the effect of hormone replacement therapy on post-menopausal urinary stress incontinence.\n Double-blind, placebo-controlled, randomised trial.\n University associated teaching hospital.\n Post-menopausal women with genuine stress incontinence, not taking hormone replacement therapy.\n Randomisation to six months therapy with oestradiol valerate 2 mg daily or placebo. Assessment prior to treatment and upon study completion with the SF-36 health status questionnaire, the Bristol Female Lower Urinary Tract Symptoms questionnaire, a one week urinary diary, one hour perineal pad test, cystometry and urethral profilometry.\n Sixty-seven women consented to participate, 33 were randomised to receive oestradiol. Mean age was 63 years. Five women failed to undergo repeat assessment, three of whom were receiving oestrogen. Six women receiving oestradiol experienced breakthrough bleeding during the six months and were subsequently treated with additional monthly progestogen. No significant effect of oestrogen over placebo was observed for any subjective or objective clinical outcome.\n This trial is one of the largest controlled studies yet reported, with the longest duration of treatment. No improvement in post-menopausal stress incontinence was demonstrated after six months therapy with oestradiol. This concurs with another study reported recently; it seems unlikely that oestrogen has a significant role to play in this condition.", "To assess the effects of hormone therapy on urinary tract infection frequency and to examine potential risk factors.\n We used data from the Heart and Estrogen/Progestin Replacement Study, a randomized, blinded trial of the effects of hormone therapy on coronary heart disease events among 2763 postmenopausal women aged 44-79 with established coronary heart disease. Participants were randomly assigned to 0.625 mg of conjugated estrogens plus 2.5 mg of medroxyprogesterone acetate or placebo and followed for a mean of 4.1 years. History of physician-diagnosed urinary tract infections and risk factors were assessed by self-report at baseline and each annual visit.\n Urinary tract infection frequency was higher in the group randomized to hormone treatment, although the difference was not statistically significant (odds ratio [OR] 1.16, 95% confidence interval [CI] 0.99, 1.37). Statistically significant risk factors for urinary tract infections in multivariable analysis included: women with diabetes on treatment (insulin OR 1.81, 95% CI 1.40, 2.34), oral medications OR 1.44, 95% CI 1.09, 1.90), poor health (OR 1.34, 95% CI 1.14, 1.57), childbirth (OR 1.38, 95% CI 1.00, 1.90), vaginal itching (OR 1.63, 95% CI 1.07, 2.50), vaginal dryness (OR 1.30, 95% CI 1.04, 1.67), and urge incontinence (OR 1.51, 95% CI 1.30, 1.75). Urinary tract infections in the previous year were strongly associated with a single urinary tract infection (OR 7.00, 95% CI 5.91, 8.29) as well as multiple urinary tract infections (OR 18.51, 95% CI 14.27, 24.02).\n Oral hormone therapy did not reduce frequency of urinary tract infections. Potentially modifiable risk factors in postmenopausal women are different from those in younger women, and include diabetes, vaginal symptoms, and urge incontinence.", "To disclose a clinical and histopathological effect of local low-dose oestradiol treatment on the vagina.\n A randomised, double-blind trial.\n Two gynaecological departments at University Hospitals.\n Forty-eight postmenopausal women scheduled for surgery because of genital prolapse.\n 25 micrograms oestradiol or placebo, administered as vaginal pessaries daily, 3 weeks prior to surgery.\n Cytological, histological and clinical changes of the vaginal mucosa.\n The thickness of the vaginal wall increased as did the oestrogenic index. No clinical effect was seen apart from decreased incidence of recurrent cystitis postoperatively.\n Preoperative oestrogen treatment has been shown to reduce the incidence of recurrent cystitis and may be needed for stimulation of vaginal mucosa; the short-term clinical effect is not convincing, however.", "Thirty-four postmenopausal stress incontinence patients were divided in two groups: 17 were treated with 0.5 mg oestriol vaginal cream for 90 days, 17 controls were treated with moisturizing cream. All had low urethral pressures and dystrophy. Treated patients showed improvement of maximum urethral pressure, urethral closure pressure, and volume at first sensation of fullness. Dystrophy was cured in most patients; in 17% incontinence was cured and in 41% subjectively improved." ]	Based on only two studies comparing vaginal oestrogens to placebo, vaginal oestrogens reduced the number of UTIs in postmenopausal women with RUTI, however this varied according to the type of oestrogen used and the treatment duration.
CD009099	[ "9729942", "10326334", "8026290" ]	[ "Evaluation of a collagen-alginate wound dressing in the management of diabetic foot ulcers.", "Diabetic foot ulcerations. A controlled, randomized comparison of two moist wound healing protocols: Carrasyn Hydrogel Wound dressing and wet-to-moist saline gauze.", "Clinical evaluation of a semipermeable polymeric membrane dressing for the treatment of chronic diabetic foot ulcers." ]	[ "Efficacy and safety of a collagen-alginate topical wound dressing (FIBRACOL Collagen-Alginate Wound Dressing) in the treatment of diabetic foot ulcers was compared with that of regular gauze moistened with normal saline. Seventy-five patients with foot ulcers were assigned randomly in a 2:1 ratio to the collagen-alginate test dressing or the gauze dressing. At the end of the study, the mean percent reduction of the wound area was 80.6% +/- 6% in the collagen-alginate dressing group and 61.1% +/- 26% in the gauze dressing group (p = .4692). Thirty-nine (78%) patients treated with the collagen-alginate dressing achieved > or = 75% wound area reduction, compared with 15 (60%) of gauze-treated patients. Complete healing was achieved in 24 (48%) of the collagen-alginate dressing group and 9 (36%) of the gauze dressing group. Wound size, when averaged over the 8-week period and with the duration of the ulcer taken into account, was reduced significantly in the collagen-alginate dressing group, as compared with the gauze dressing group (df = 1, p = .0049). It is concluded that the collagen-alginate test dressing is as or more effective and safe as the currently used treatment.", "nan", "To evaluate the utility of a semipermeable polymeric membrane dressing for the treatment of chronic diabetic foot ulcers.\n Nineteen subjects with either insulin-dependent diabetes mellitus (IDDM) or non-insulin-dependent diabetes mellitus (NIDDM) and foot ulcers were randomly assigned to the polymeric dressing or conventional wet-to-dry saline dressings. Subjects had foot ulcer site measurements performed every 3 weeks. The subjects using conventional therapy were allowed to cross over to polymeric dressing after 2 months.\n At the end of 2 months, in the patients using the polymeric dressing, ulcer size was reduced to 35 +/- 16% of baseline. The patients on conventional therapy had an ulcer size of 105 +/- 28% of baseline (P < 0.03, polymeric vs. conventional). Patients initially treated with wet-to-dry saline were crossed over into the polymeric membrane treatment and demonstrated a decrease to 35 +/- 11% of baseline size (p < 0.02) after an additional 2 months.\n The semipermeable polymeric membrane dressing is a useful therapeutic option for treating uncomplicated chronic diabetic foot ulcers." ]	Currently there is no research evidence to suggest that any type of hydrocolloid wound dressing is more effective in healing diabetic foot ulcers than other types of dressing. Decision makers may wish to consider aspects such as dressing cost and the wound management properties offered by each dressing type e.g. exudate management.
CD001816	[ "1841829", "3288866", "11445103" ]	[ "Prevention of necrotizing enterocolitis in neonates at risk by oral administration of monomeric IgG.", "Prevention of necrotizing enterocolitis in low-birth-weight infants by IgA-IgG feeding.", "Enteral human IgG for prevention of necrotising enterocolitis: a placebo-controlled, randomised trial." ]	[ "Necrotizing enterocolitis (NEC) represents one of the major causes of morbidity in low-birth-weight (LBW) preterm infants. This randomized clinical trial evaluated the efficacy of an oral immunoglobulin preparation (containing monomeric IgG in a concentration of 90%) in reducing the incidence of NEC in infants of LBW for whom maternal breast milk was not available. One hundred and thirty-two formula-fed newborns with a birth weight less than or equal to 1,500 g or a gestational age less than or equal to 34 weeks were randomly studied. Five hundred mg of IgG pro die, subdivided into 5 doses, were given orally to the test group of 65 neonates during the first 2 weeks of life. Although the number of infants included in this group is limited, the results of this study are encouraging: during the first 15 days after birth, none of the subjects developed NEC, while 4 cases were confirmed in the untreated control group. It, therefore, seems possible that oral monomeric IgG administration may prevent the development of NEC in LBW infants.", "In a randomized clinical trial, we evaluated the efficacy of an oral immunoglobulin preparation (73 percent IgA and 26 percent IgG) in reducing the incidence of necrotizing enterocolitis in infants of low birth weight for whom breast milk from their mothers was not available. A total of 434 infants weighing between 800 and 2000 g were eligible for entry in the study. Of these, 255 were withdrawn - 234 during the first week of the study because breast milk from their mothers became available (123 in the treatment group and 111 in the control group), and 21 because of violations of protocol or because breast milk became available after the first week. The duration of follow-up was 28 days. Among the infants for whom breast milk did not become available during the study, there were no cases of necrotizing enterocolitis among the 88 receiving oral IgA-IgG, as compared with six cases among the 91 control infants (P = 0.0143). Of the infants withdrawn from the study, two assigned to the control group had necrotizing enterocolitis. We conclude that the oral administration of IgA-IgG may prevent the development of necrotizing enterocolitis in low-birth-weight infants.", "Neonatal necrotising enterocolitis is a serious, commonly fatal disease in premature neonates. Although feeding with expressed breast milk and other good nursery practices are partly protective, preventive measures are needed. Treating neonates enterally with a mixture of human IgA and IgG, prepared from donated blood, has been claimed to protect against necrotising enterocolitis. However, no IgA preparation is available in Australia. Our aim, therefore, was to identify whether or not enteral IgG could prevent the disorder.\n We did a multicentre, double-blind, placebo- controlled trial. We randomly assigned 768 infants to receive human IgG 1200 mg/kg daily, and 761 to receive placebo, for up to 28 days. Treatment began at the same time as enteral feeding. The primary outcome measure was the proportion of infants who developed definite necrotising enterocolitis during the trial, and any deaths that resulted from the disorder in the treatment and placebo groups. Analysis was on an intention-to-treat basis.\n 43 infants developed definite necrotising enterocolitis in the IgG group, ten of whom died. In the placebo group, 41 infants contracted the disorder and six died (p=0.47). 25 infants on IgG and 36 on placebo had suspect necrotising enterocolitis (p=0.14).\n Supplementation of enteral feeds with human IgG does not reduce necrotising enterocolitis." ]	Based on the available trials, the evidence does not support the administration of oral immunoglobulin for the prevention of NEC. There are no randomised controlled trials of oral IgA alone for the prevention of NEC.
CD001188	[ "10343421", "15991780", "21661618", "8442622", "11802453", "21800642", "16595098", "7852062", "16027567", "2556540", "11900495", "10800972", "17184783", "15586136", "15586837", "18465176", "18304363", "11082801", "2202445", "17995993", "19959695", "16182355", "1873454", "8602320", "16873594", "9735523", "3592033", "12460525", "10514155", "18689856", "1414430", "17372796", "15533536", "9046892", "12622686", "19524389", "12775857", "16788278", "10600434", "10617734", "18407003" ]	[ "Randomized trial of nurse-assisted strategies for smoking cessation in primary care.", "A randomised controlled trial to evaluate the efficacy of a nurse-provided intervention for hospitalised smokers.", "Nurse case-managed tobacco cessation interventions for general hospital patients: results of a randomized clinical trial.", "Nurse-assisted counseling for smokers in primary care.", "[The effect of smoking cessation counseling at health checkup].", "[A pre assessment for nursing intervention to support tobacco cessation in patients hospitalized for cardiac problems: a pilot study (So-Live)].", "[Effectiveness of a programme of intensive tobacco counselling by nursing professionals].", "A comparison of nursing interventions for smoking cessation in adults with cardiovascular health problems.", "The effectiveness of a nursing inpatient smoking cessation program in individuals with cardiovascular disease.", "Randomized controlled trial of anti-smoking advice by nurses in general practice.", "Efficacy of resident training in smoking cessation: a randomized, controlled trial of a program based on application of behavioral theory and practice with standardized patients.", "Implementation and effectiveness of a brief smoking-cessation intervention for hospital patients.", "Does additional support by nurses enhance the effect of a brief smoking cessation intervention in people with moderate to severe chronic obstructive pulmonary disease? A randomised controlled trial.", "Motivational interviewing as a smoking cessation intervention for patients with cancer: randomized controlled trial.", "Results of a randomized controlled trial of intervention to implement smoking guidelines in Veterans Affairs medical centers: increased use of medications without cessation benefit.", "A computerized aid to support smoking cessation treatment for hospital patients.", "Acceptability and effectiveness of opportunistic referral of smokers to telephone cessation advice from a nurse: a randomised trial in Australian general practice.", "The feasibility of a nurse-managed, peer-led tobacco cessation intervention among HIV-positive smokers.", "The effectiveness of two smoking cessation programmes for use in general practice: a randomised clinical trial.", "Proactive interventions for smoking cessation in general medical practice: a quasi-randomized controlled trial to examine the efficacy of computer-tailored letters and physician-delivered brief advice.", "Effectiveness of a nurse-managed, lay-led tobacco cessation intervention among ohio appalachian women.", "Home health care nurses as a new channel for smoking cessation treatment: outcomes from project CARES (Community-nurse Assisted Research and Education on Smoking).", "A randomized trial of smoking cessation interventions in general practice in Italy.", "A randomized controlled trial of smoking cessation intervention in pregnancy in an academic clinic.", "Integrated tobacco cessation counseling in a diabetes self-management training program: a randomized trial of diabetes and reduction of tobacco.", "[Smoking cessation for hospitalized patients: a quasi-experimental study in Quebec].", "Evaluation of a minimal-contact smoking cessation intervention in an outpatient setting.", "Improving family physicians' use of evidence-based smoking cessation strategies: a cluster randomization trial.", "Behavioural counselling in general practice for the promotion of healthy behaviour among adults at increased risk of coronary heart disease: randomised trial.", "In-practice management versus quitline referral for enhancing smoking cessation in general practice: a cluster randomized trial.", "Does nurse counseling or offer of nicotine gum improve the effectiveness of physician smoking-cessation advice?", "Randomized controlled trial of a computer-based, tailored intervention to increase smoking cessation counseling by primary care physicians.", "The TEAM project: the effectiveness of smoking cessation intervention with hospital patients.", "Smoking cessation in hospitalized patients. Results of a randomized trial.", "Pediatric-based smoking cessation intervention for low-income women: a randomized trial.", "Impact of a brief motivational smoking cessation intervention the Get PHIT randomized controlled trial.", "Clinical trial comparing nicotine replacement therapy (NRT) plus brief counselling, brief counselling alone, and minimal intervention on smoking cessation in hospital inpatients.", "Effectiveness of a low-intensity intra-worksite intervention on smoking cessation in Japanese employees: a three-year intervention trial.", "The effectiveness of a directly mailed smoking cessation intervention to Australian discharged hospital patients.", "The impact of a brief intervention on maternal smoking behavior.", "Web-based smoking-cessation programs: results of a randomized trial." ]	[ "Brief advice to stop smoking from general practitioners (GPs) has been repeatedly shown to increase smoking cessation by a small, but measurable amount. Some studies have suggested that adding more intensive interventions to brief advice may increase its effectiveness, but it is unclear whether this is true in general practice.\n To determine whether brief advice from a doctor together with counselling and follow-up from a trained practice nurse is more effective than brief advice alone in helping people to stop smoking.\n The design was a randomized controlled trial. Four hundred and ninety-seven general practice patients aged older than 18 years and smoking at least one cigarette per day in six general practices in Oxfordshire, Berkshire, and Buckinghamshire were randomized to one of two interventions: brief verbal or written advice from a GP plus extended counselling and follow-up from a trained practice nurse; brief advice from a GP alone. The primary outcome was sustained abstinence from smoking at three and 12 months. A secondary outcome was forward movement in the stages of change cycle.\n The proportion showing sustained abstinence was 3.6% in the extended counselling group, and 4.4% in the brief advice group (difference = -0.8%; 95% confidence interval = -4.3% to 2.6%). Seventy-four (30%) of those randomized to extended counselling actually took up this offer. No significant progression in stages of change was detected between the two groups.\n In unselected general practice patients who smoke, brief advice from a GP combined with intensive intervention and follow-up by a practice nurse is no more effective than brief advice alone.", "Does the provision of a nurse-based intervention lead to smoking cessation in hospital patients?\n At tertiary teaching hospital in Newcastle, Australia, 4,779 eligible (aged 18-80, admitted for at least 24 hours, and able to provide informed consent) and consenting (73.4%) in-patients were recruited into a larger cross-sectional survey. 1,422 (29.7%) smokers (in the last 12 months) were randomly assigned to control (n = 711) or intervention group (n = 711). The brief nurse-delivered intervention incorporated: tailored information, assessment of withdrawal, offer of nicotine replacement therapy, booklets, and a discharge letter. Self-reported cessation at 12 months was validated with CO and salivary cotinine.\n There were no significant differences between groups in self-reported abstinence at three or 12 months post intervention, based on an intention to treat analysis. At three months, self-reported abstinence was 27.3% (I) and 27.5% (C); at 12 months was 18.5% (I) and 20.6% (C). There were no differences in validation of self-report between intervention and control groups at 12 months.\n This brief nurse-provided in-patient intervention did not significantly increase the smoking cessation rates compared with the control group at either three or 12-month follow-up.\n A systematic total quality improvement model of accountable outcome-focused treatment, incorporating assertive physician-led pharmacotherapy, routine assessment and recording of nicotine dependence (ICD 10 coding), in- and outpatient services and engagement from multidisciplinary teams of health professionals may be required to improve treatment modalities for this chronic addictive disorder.", "This randomized clinical trial was designed to test the efficacy of intensive versus brief smoking cessation interventions for hospital patients. The interventions included advice and pamphlets for Brief and bedside counselling, take-home materials, and 7 post-discharge telephone counselling calls over 2 months for Intensive. Confirmed 1-year abstinence was 28% for Intensive (85/301) and 24% for Brief (76/315). Abstinence was significantly higher for patients who did not use pharmacotherapy (36%) versus those who did (16%) and for patients with CVD (40%) versus other diagnoses (20%). Because this was a replication trial, benchmarks for planning can be suggested: 12% to 15% recruitment of identified smokers, 90% plus completion for Intensive, 15% drop-out, and 75% abstinence corroboration. The results consolidate findings for general inpatients, including expected absolute abstinence and treatment outcomes, the effect of CVD patients on outcomes, the reproducibility of high abstinence in a universal health-care system, and the need for more research to inform practice.", "Physician-delivered advice to stop smoking is effective, but time demands often reduce the number of smokers who receive assistance. We evaluated three nurse-assisted interventions designed to minimize physician burden and increase counseling in primary care settings.\n Randomized controlled trial with a 12-month follow-up.\n Internal medicine and family practice offices in a health maintenance organization.\n Smokers (n = 3161) who were patients of participating physicians or other medical care providers (n = 60).\n Medical care providers delivered a 30-second stop-smoking prompt to 2707 smokers and referred them to an on-site nurse smoking counselor. The nurse randomly provided a two-page pamphlet (advice control) or one of three nurse-assisted interventions: 1) self-quit training; 2) referral to a group cessation program; or 3) a combination of self-quit training and referral. Each nurse-delivered intervention included a 10-minute video, written materials, and a follow-up phone call.\n Physicians delivered brief advice to 86% of identified smokers during the 1-year program. The proportion of participants reporting abstinence after both 3 and 12 months of follow-up nearly doubled (P = 0.01) for the nurse-assisted self-quit (7.1%), group-referral (7.6%), and combination (6.9%) interventions, compared to brief physician advice alone (3.9%) (P < 0.05). Saliva cotinine tests confirmed these effects (P < 0.004), although quit rates were lower (3.4%, 4.7%, 4.3%, and 2.3%, respectively) because roughly one half of quitters chose not to provide a saliva sample and were counted as smokers.\n Involving nurses in counseling smokers reduces physician burden, makes counseling more likely, and significantly increases cessation rates compared with brief physician advice alone.", "Smoking cessation counseling is an important element of tobacco control in the workplace, but it is not easy to persuade workers to stop smoking. We performed a controlled intervention trial to evaluate the effectiveness of a new cessation program developed by Nakamura et al., which consisted of one brief individual counseling session and 4 follow-up telephone calls. Two hundred and twenty-eight smokers who visited our center for an annual health checkup were randomly divided into two group: 117 were assigned to the intervention group, and 111 were controls. Smoking status questionnaires were administered to assess the smoking habit of each subject and to evaluate their stages of change toward smoking cessation before the counseling session. Stage-matched cessation counseling was then provided to the intervention group by nurses who had completed training courses for this program. During the counseling session, carbon monoxide in expired air and nicotine metabolites in urine were measured to enhance self-perception of smoking. Only those clients who set a quit date during their counseling sessions received follow-up telephone calls. It was easy to implement this program (15 to 20 minutes long) during a health checkup. No significant differences were observed in the baseline characteristics of the two groups. The cross-sectional smoking cessation rates at 6 months and 1 year of follow-up were 6.2 times higher in the intervention group than in the control group. The continuous smoking cessation rate at 1 year of follow-up was 7.6 times higher in the intervention group than in the control group. In the intervention group, the lower level of nicotine metabolites in urine and higher smoking stage were related to cessation success, but other baseline characteristics were similar in those who quit smoking and those who did not. The effectiveness and easy applicability of this cessation program was proved in the present study. Further examinations in various settings are expected to clarify the effectiveness of this program.", "The aim of this study was to evaluate the effect of a smoking cessation intervention provided after discharge from a specialized cardiac hospital.\n A randomized pilot study (N = 40); after discharge, the experimental group (EG) received 6 phone calls from a nurse specialized in tobacco cessation counselling.\n Patients in the EG showed improved scores on two aspects of illness representations (perceive their illness as chronic and reported less negative emotional representations). No significant difference in smoking cessation was observed at 6 months (p = 0.72).\n The non-significant difference may be explained in part by the smoking characteristics within this sample exemplifying the more nicotine dependent \"hard core\" smokers who persist in their smoking habits despite the serious health consequences incurred by continued smoking. This population of smokers may require a more intensive, specialized intervention to achieve smoking cessation.", "To determine the effectiveness of a systematic intensive tobacco counselling programme conducted by nursing professionals.\n Randomised clinical trial with control.\n Primary care nursing and medical consultations.\n Smokers requesting help in our centre's medical clinics during the recruitment period, up to the sample size required (125). Inclusion criteria were: aged between 18 and 70, people who smoked during the preceding month any number of cigarettes a day, and a score over 7 on the Richmond test.\n The patients recruited were randomised, according to the clinic from which they came, to the group that received brief counselling from the doctor (control group) or to the group that received brief counselling plus nursing follow-up (intervention group). Follow-up visits were programmed in this latter group for up to 3 months after giving up smoking.\n Abstinence at 12 and 24 months.\n The effectiveness of the intervention considered as the rate of abstinence at 12 months was 13.8% (95% CI, 6.5-24.7) in the control group and 6.7% (95% CI, 1.8-16.2) in the intervention group, with no significant differences between the two.\n In smokers seen in primary care, the effectiveness of a programme of intensive tobacco counselling by nursing staff is no more effective than the doctor's brief, one-off counselling. Brief counselling has a better cost-effectiveness relationship than intensive counselling.", "To examine the relative effectiveness of three different presentations of a smoking cessation program on the smoking behavior of adults with cardiovascular health problems.\n A 2 x 2 x 2 x 4 experimental design with stratification by sex, smoking history, and a cardiovascular event, and randomization to Individual, Group, Written, or No Intervention groups.\n Six community hospital classrooms.\n 255 nonhospitalized adults. THEORETIC FRAMEWORK: Interaction Model of Client Health Behavior.\n Study Intake: Professional referral form, demographic questionnaire, smoking habits questionnaire, health history, perceived threat survey, perceived health status. Follow up: smoking cessation and health questionnaire, saliva thiocyanate testing.\n At 12-month follow-up, a nurse-client interaction was more effective than written self-help materials; however, smoking cessation rates were highest in the No Intervention control group, possibly related to having had coronary artery bypass graft surgery. Variables positively related to quitting were being male and married and having a higher income. With baseline factors considered, a quitter was most likely to be male and less than 48 years of age, have a high degree of perceived threat relative to medical diagnosis, and be in the individual intervention group. Only partial support for the study hypotheses was found.", "Smoking is an important risk factor for cardiovascular disease (CVD), and quitting is highly beneficial. Yet, less than 30% of CVD patients stop smoking. Relapse-prevention strategies seem most effective when initiated during the exacerbation of the disease.\n A nurse-delivered inpatient smoking cessation program based on the Transtheoretical Model with telephone follow-up tailored to levels of readiness to quit smoking was evaluated on smoking abstinence and progress to ulterior stages of change.\n Participants (N = 168) were randomly assigned by cohorts to inpatient counseling with telephone follow-up, inpatient counseling, and usual care. The inpatient intervention consisted of a 1-hr counseling session, and the telephone follow-up included 6 calls during the first 2 months after discharge. The nursing intervention was tailored to the individual's stage of change. End points at 2 and 6 months included actual and continuous smoking cessation rates (biochemical markers) and increased motivation (progress to ulterior stages of change).\n Assuming that surviving patients lost to follow-up were smokers, the 6-month smoking abstinence rate was 41.5% in the inpatient counseling with telephone follow-up group, compared with 30.2% and 20% in the inpatient counseling and usual care groups, respectively (p = .05). Progress to ulterior stages of change was 43.3%, 32.1%, and 18.2%, respectively (p = .02). Stage of change at baseline and intervention predicted smoking status at 6 months.\n This tailored smoking cessation program with telephone follow-up significantly increased smoking cessation at 6 months, and progression to ulterior stages of change. The telephone follow-up was an important adjunct. It is, therefore, recommended to include such comprehensive smoking cessation programs within hospital settings for individuals with CVD.", "Practice nurses are playing an increasingly prominent role in preventive care, including the provision of anti-smoking advice during routine health checks. A randomized controlled trial was designed to assess the effectiveness of anti-smoking advice provided by nurses in helping smokers to stop smoking. A total of 14,830 patients aged 16-65 years from 11 general practices completed a brief questionnaire on general health, including smoking status, at surgery attendance. The doctor identified 4330 smokers and randomly allocated 4210 to control or intervention groups. The doctor asked those in the intervention group to make an appointment with the practice nurse for a health check. The attendance rate at the health check was 26%. Smokers were sent follow-up questionnaires at one month and one year, and those who did not respond to two reminders were assumed to have continued to smoke. There was no significant difference in reported cessation between the intervention and control groups at one month or one year. However, there was a significant difference in the proportion of patients who reported giving up within one month and who had not lapsed by one year--0.9% in controls and 3.6% in the intervention group (P less than 0.01). Nevertheless, the effect of the nurse intervention itself may be small as the sustained cessation rate in attenders was only 42.4% higher than in non-attenders. The deception rate in reporting cessation, as measured by urinary cotinine, was of the order of 25%.", "New educational programs must be developed to improve physicians' skills and effectiveness in counseling patients about smoking cessation.\n To assess the efficacy of an educational program based on behavioral theory, active learning methods, and practice with standardized patients in helping patients abstain from smoking and changing physicians' counseling practices.\n Cluster randomized, controlled trial.\n Two general internal medicine clinics in Switzerland.\n 35 residents and 251 consecutive smoking patients.\n A training program administered over two half-days, during which physicians learned to provide counseling that matched smokers' motivation to quit and practiced these skills with standardized patients acting as smokers at different stages of change. The control intervention was a didactic session on management of dyslipidemia.\n Self-reported abstinence from smoking at 1 year of follow-up, which was validated by exhaled carbon monoxide testing at one clinic; score of overall quality of counseling based on use of 14 counseling strategies; patient willingness to quit; and daily cigarette consumption.\n At 1 year of follow-up, abstinence from smoking was significantly higher in the intervention group than in the control group (13% vs. 5%; P = 0.005); this corresponded to a cluster-adjusted odds ratio of 2.8 (95% CI, 1.4 to 5.5). Residents who received the study training provided better counseling than did those who received the control training (mean score, 4.0 vs. 2.7; P = 0.002). Smokers' willingness to quit was also higher in the intervention group (94% vs. 80%; P = 0.007). A nonsignificant trend toward lower daily cigarette consumption in the intervention group was observed.\n A training program in smoking cessation administered to physicians that was based on behavioral theory and practice with standardized patients significantly increased the quality of physicians' counseling, smokers' motivation to quit, and rates of abstinence from smoking at 1 year.", "Previous research has documented that hospital-based smoking-cessation counseling is efficacious and cost-effective when delivered by research staff. This study evaluated the implementation and effectiveness of this intervention program when delivered by respiratory therapists chosen from the regular hospital staff.\n A total of 1,173 hospitalized smokers were randomly assigned to either usual care or a stage-based bedside counseling program supplemented with a videotape, self-help materials, and a follow-up telephone call.\n Using an intent-to-treat analysis and counting those lost to follow-up as smokers, we did not find a significant difference in outcome between intervention (14.2% reported being abstinent for > or =6 months at the 1-year follow-up) and usual care conditions (13.6% abstinence). Process analyses revealed that these results were due to a combination of failure to reach many patients and reduced effectiveness of respiratory therapist interventionists compared with experienced professional counselors in a previous study conducted in the same hospitals.\n We recommend implementation of hospital-based smoking-cessation counseling by professional counselors whose primary responsibility is to deliver the intervention. Recommendations for future research and for innovative ways to reach hospitalized smokers who are not receiving intervention are discussed.", "Smoking cessation is the primary disease modifying intervention for chronic obstructive pulmonary disease (COPD).\n A Regional Respiratory Centre (RRC) out-patient department in Northern Ireland.\n A randomised controlled trial (RCT) evaluated the effectiveness of brief advice alone or accompanied by individual nurse support or group support facilitated by nurses. Smoking status was biochemically validated and stage of change, nicotine addiction and dyspnoea were recorded at 2, 3, 6, 9 and 12 months.\n Ninety-one cigarette smokers with COPD were enrolled in the study (mean age 61 years, 47 female).\n After 12 months cessation rates were not significantly different between groups (p=0.7), but all groups had a significant reduction in their nicotine addiction (p=0.03-0.006). No changes in subjects' motivation or dyspnoea were detected over the 12 months.\n Patients with COPD were unable to stop smoking regardless of the type of support they received. Harm reduction may be a more appropriate goal than complete cessation for intractable smokers and nurses must evaluate their role in this arena.", "Smoking cessation of patients with cancer can improve treatment efficacy and survival.\n To determine whether a motivational interviewing intervention increased successful smoking cessation attempts of patients with cancer attending a South Australian public hospital, as compared with usual care.\n A randomized controlled trial was used to study 137 patients with mixed cancer sites, including 74 intervention patients and 63 control patients. The motivational interviewing intervention was delivered over a 3-month period. The intervention included a visit with a smoking cessation counselor, provision of smoking cessation booklets, nicotine replacement therapy, family advice to quit, and an in-person or telephone follow-up conversation.\n At the 6-month follow-up visit, an intention-to-treat analysis found no difference in biochemically confirmed 3-month prevalence quit rates between the intervention (5%) and control (6%) groups. A sensitivity analysis using more lenient criteria indicated quit rates of 29% for the intervention group and 18% for the control group (p = .32). The predictors of smoking cessation at 6 months for all the patients included a smoking-related cancer site, more cessation attempts in the year before enrollment in the study, and no radiation therapy.\n Future efforts to improve smoking cessation in this patient group might focus on the delivery of more direct methods for encouraging spouse cessation and support to the patient in quitting, and the use of bupropion (Zyban) as an adjunct to cessation for this heavy smoking patient group.", "The AHRQ Clinical Practice Guideline for Treating Tobacco Use and Dependence recommends screening and treatment of all tobacco users. Effective methods to implement recommendations are needed because simple guideline dissemination does not necessarily result in changes in practice.\n The Guideline Implementation for Tobacco (GIFT) study tested an organizational intervention to improve Guideline implementation.\n GIFT randomized 20 Veterans Affairs medical centers to intervention or control conditions. We trained prime movers at each site to improve identification of smoking status, promote primary care interventions and increase availability of smoking cessation medications. Sites and patients were evaluated before and after intervention.\n GIFT included 20 Veterans Affairs medical centers and 5678 subjects.\n Data regarding smoking status, delivery of treatment, medication use, and smoking cessation were collected from participant surveys, medical record review, survey of site leaders, and Pharmacy Benefits Management.\n The intervention did not increase participant report of being asked about smoking status or receipt of counseling. It did increase the rate of identification of smoking status in the medical record (P = 0.0001) but did not increase the rate of counseling to stop smoking. Site level data showed no increase in the number of patients receiving smoking cessation medications or dollars spent on medications. Individual smoker data showed a significant increase in the use of medications for smoking cessation in intervention sites (odds ratio = 6.89, P < 0.0001); however, only a small minority of smokers received medication even after the intervention. There was no difference in smoking cessation rates between participants at the intervention and treatment sites.\n We conclude that improvements in smoking cessation rates are likely to require more intensive intervention in this population.", "Hospital-based interventions promote smoking cessation after discharge. Strategies to deliver these interventions are needed, especially now that providing smoking cessation advice or treatment, or both, to inpatient smokers is a publicly reported quality-of-care measure for US hospitals.\n To assess the effect of adding a tobacco order set to an existing computerized order-entry system used to admit Medicine patients to 1 hospital.\n Pre-post study.\n Proportion of admitted patients who had smoking status identified, a smoking counselor consulted, or nicotine replacement therapy (NRT) ordered during 4 months before and after the change. In 4 months after implementation, the order set was used with 76% of Medicine admissions, and a known smoking status was recorded for 81% of these patients. The intervention increased the proportion of admitted patients who were referred for smoking counseling (0.8 to 2.1%) and had NRT ordered (1.6 to 2.5%) (p < .0001 for both). Concomitantly, the hospital's performance on the smoking cessation quality measure improved.\n Adding a brief tobacco order set to an existing computerized order-entry system increased a hospital's provision of evidence-based tobacco treatment and helped to improve its performance on a publicly reported quality measure. It provides a model for US hospitals seeking to improve their quality of care for inpatients.", "GPs often lack time to provide intensive cessation advice for patients who smoke. This study aimed to determine the effectiveness of opportunistic referral of smokers by their GP for telephone cessation counselling by a trained nurse.\n Adult smokers (n = 318) attending 30 GPs in South Western Sydney, Australia were randomly allocated to usual care or referral to a telephone-based program comprising assessment and stage-based behavioural advice, written information and follow-up delivered by a nurse. Self-reported point prevalence abstinence at six and 12 months was compared between groups. Characteristics of patients who accepted and completed the intervention were investigated.\n Of 169 smokers randomised to the intervention, 76 (45%) consented to referral. Compared with smokers in 'pre-contemplation', those further along the stage-of-change continuum were significantly more likely to consent (p = 0.003). Those further along the continuum also were significantly more likely to complete all four calls of the intervention (OR 2.6, 95% CI: 0.8-8.1 and OR 8.6, 95% CI: 1.7-44.4 for 'contemplation' and 'preparation' respectively). At six months, there was no significant difference between groups in point prevalence abstinence (intention to treat) (9% versus 8%, p = 0.7). There was no evidence of differential intervention effectiveness by baseline stage-of-change (p = 0.6) or patient sex (p = 0.5). At 12 months, point prevalence abstinence in the intervention and control groups was 8% and 6% respectively (p = 0.6).\n Acceptance of opportunistic referral for nurse delivered telephone cessation advice was low. This trial did not demonstrate improved quit rates following the intervention. Future research efforts might better focus support for those patients who are motivated to quit. AUSTRALIAN CLINICAL TRIALS REGISTRY NUMBER: ACTRN012607000091404.", "The purpose of this pilot study was to examine the effectiveness of an 8-week, nurse-managed, peer-led smoking cessation intervention among HIV-positive smokers. The intervention was based on the Agency for Health Care Policy and Research Smoking Cessation Clinical Practice Guideline and was delivered by an ex-smoker who was HIV positive and had been trained by an advanced practice nurse to deliver cessation counseling. Eight male HIV-positive smokers were assigned to the intervention group and received (a) 21 mg nicotine patch therapy for 6 weeks, (b) weekly face-to-face or telephone counseling, and (c) skills training that included substitute strategies for dealing with not smoking. Those participants assigned to the control group received written self-help materials for smoking cessation. Abstinence rates at end of intervention and 8 months were compared between groups. At end of treatment, 62.5% of intervention group participants were biochemically confirmed as abstinent from smoking compared with 0% in the control group. Eight-month abstinence rates were 50% among the intervention group compared with 0% in the control group.", "To evaluate a structured, behavioural change, smoking cessation intervention designed for use within general practice.\n Randomised controlled clinical trial.\n General practices in Newcastle, Australia.\n 311 Patients identified as smokers by a screening question were enrolled in the study. Of these, 101 were assigned to a structured behavioural change programme, 104 to a simple advice programme adapted from previous research, and 106 to a control group. No significant differences were found between groups for demographic and smoking related variables before the study.\n Patients in the simple advice group received a brief statement of advice from the general practitioner as well as three pamphlets; those in the structured intervention group were given strategies which included attitude and behavioural change programmes as well as techniques to aid compliance. The amount of smoking in all groups was assessed by self reports with validation by measurement of salivary cotinine concentrations.\n Significant increase in cessation rates.\n Significant differences between controls and the structured behavioural change group were found at the one month follow up, but only for self reported abstinence. The simple advice programme did not produce any significant differences over the control group. General practitioner evaluation of the structured programme highlighted difficulties in relation to the duration of the intervention. Overall the structured programme in its present form did not appear to be an effective programme for use within general practice.", "To test the efficacy of (i) computer-generated tailored letters and (ii) practitioner-delivered brief advice for smoking cessation against an assessment-only condition; and to compare both interventions directly.\n Quasi-randomized controlled trial.\n A total of 34 randomly selected general practices from a German region (participation rate 87%).\n A total of 1499 consecutive patients aged 18-70 years with daily cigarette smoking (participation rate 80%).\n The tailored letters intervention group received up to three individualized personal letters. Brief advice was delivered during routine consultation by the practitioner after an onsite training session. Both interventions were based on the Transtheoretical Model of behaviour change.\n Self-reported point prevalence and prolonged abstinence at 6-, 12-, 18- and 24-month follow-ups.\n Among participants completing the last follow-up, 6-month prolonged abstinence was 18.3% in the tailored letters intervention group, 14.8% in the brief advice intervention group and 10.5% in the assessment-only control group. Assuming those lost to follow-up to be smokers, the rates were 10.2%, 9.7% and 6.7%, respectively. Analyses including all follow-ups confirmed statistically significant effects of both interventions compared to assessment only. Using complete case analysis, the tailored letters intervention was significantly more effective than brief advice for 24-hour [odds ratio (OR) = 1.4; P = 0.047] but not for 7-day point prevalence abstinence (OR = 1.4; P = 0.068) for prolonged abstinence, or for alternative assumptions about participants lost to follow-up.\n The study demonstrated long-term efficacy of low-cost interventions for smoking cessation in general practice. The interventions are suitable to reach entire populations of general practices and smoking patients. Computer-generated letters are a promising option to overcome barriers to provide smoking cessation counselling routinely.", "The purpose of this study was to evaluate a nurse-managed, lay-led tobacco cessation intervention delivered to adult women in Ohio Appalachia.\n A randomized controlled experimental design included intervention participants (n = 147) enrolled in a nurse-managed, lay-led protocol that incorporated nicotine replacement and behavioral counseling. Control participants (n = 155) received a personalized letter from their clinic physician, who advised them to quit smoking and requested they schedule a clinic appointment to discuss cessation.\n Self-reported and cotinine-validated quit rates were significantly higher among intervention group participants compared with control group participants at 3-and 6-month follow-up (P < 0.02). At 12 months, self-reported abstinence was 19.1% (intervention group) and 9.0% (control group), with cotinine-validated rates of 12.2% and 7.1%, respectively (P = 0.13). Prolonged abstinence rates were significantly different between groups at 3, 6, and 12 months (P < 0.02). Logistic regression analyses indicated adjusted odds of cotinine-validated quitting was associated with cigarette consumption per day (odds ratio, 0.94; 95% confidence interval, 0.89-0.99) and Center for Epidemiologic Studies Depression Scale score > or = 16 (odds ratio, 0.39; 95% confidence interval, 0.17-0.90).\n A lay-led approach that is managed by a nurse may serve as an effective cessation strategy among this high-risk population. Additional efforts are needed to sustain long-term abstinence, even after intensive intervention.", "Clinical guidelines for smoking cessation may not be sufficient for helping some subgroups of smokers quit. Incorporating smoking cessation into home-based medical care can proactively reach high-risk smokers who may not have access to (or spontaneously seek) smoking cessation.\n Home health care nurses (N = 98) were randomly assigned to deliver either Motivational Enhancement (ME; Motivational Interviewing + Carbon Monoxide Feedback) or Standard Care (AHCPR Guidelines for smoking cessation) to their patients. Seventy percent of patients were eligible and willing to participate (N = 273; 54% female, mean age = 57 years, 83% Caucasian, 41% < high school education). The study was conducted in Providence, RI, USA from 1998 to 2003.\n Biochemically verified continuous abstinence rates at the 12-month follow-up were 4.2% (SC) and 8.7% (ME) for intent to treat analyses, and 5.2% (SC) and 11.8% (ME) using all available cases (P > 0.05). ME reported more quit attempts and significantly greater reductions in the number of cigarettes smoked per day at all follow-ups through 12 months of post-treatment (all P values < 0.05).\n Use of an existing public health channel such as home health care to reach smokers who vary in their motivation to quit could have the potential for large public health impact.", "The purpose of this study was to examine the effectiveness of different practice-based approaches to assist patients of primary care physicians to quit smoking and sustain cessation. Forty-four nonsmoking general practitioners volunteered for the study. After a period of training, they randomized 923 smoking clients, unselected for motivation toward quitting, to four different intervention groups: (i) minimal intervention, consisting of one single counselling session and a brief handout on quitting techniques; (ii) repeated counselling including reinforcing sessions at Months 1, 3, 6, and 9; (iii) repeated counselling and use of nicotine gum; and (iv) repeated counselling and spirometry. Biochemically validated smoking status was assessed at six and 12 months after recruitment. The proportion of verified quitters at 12 months was 4.8 percent among subjects randomized to the minimal intervention group, compared to 5.5 percent, 7.5 percent, and 6.5 percent among those randomized to the three repeated-counselling groups. In no treatment group was the outcome significantly different from that for one-time counselling at the (P less than 0.05) level. Lack of power, contamination, and low attendance at reinforcing sessions should be taken into account in interpreting the results.", "To evaluate the effectiveness of a physician-based intervention to promote smoking cessation during pregnancy, we conducted this randomized controlled trial in the resident-staffed prenatal clinics at the University of North Carolina Women's Hospital . Two hundred fifty prenatal patients who smoked were enrolled at their first visit and randomly assigned to the intervention or the usual-care group. Resident physicians provided self-help materials to intervention subjects and used a script to set goals with them at each prenatal visit. Subjects who set quit dates were contacted by volunteer cessation counselors. To verify smoking status, subjects provided a self-report and breath carbon monoxide (CO) sample at each visit. Controls were similarly assessed at enrollment and at three additional predetermined intervals. Twenty percent of intervention subjects and 10% of controls reported cessation, which was verified by CO level (P = .052). Fifty-one percent of subjects reduced their consumption by half or more, compared with 30% of controls (P = .002). The intervention is effective in promoting smoking cessation and reduction. In addition, this technique is inexpensive, readily accepted by staff, and efficient.", "The purpose of this study was to evaluate the impact of a tobacco cessation intervention using motivational interviewing on smoking cessation rates during diabetes self-management training (DSMT).\n A randomized controlled trial was conducted with subjects recruited from an ongoing type 2 diabetes adult education program at a large diabetes center. A total of 114 subjects were randomized to intervention (n = 57; face-to-face motivational interviewing plus telephone counseling and offering of medication) or standard care (n = 57). Outcome measures included tobacco cessation rates, mean number of cigarettes smoked, A1C, weight, blood pressure, and lipids.\n Intensive intervention using motivational interviewing integrated into a standard DSMT program resulted in a trend toward greater abstinence at 3 months of follow-up in those receiving the intervention. However, this same trend was not observed at 6 months. The addition of this structured smoking cessation intervention did not negatively affect either diabetes education or other measures of diabetes management, including A1C values.\n Structured tobacco cessation efforts can be readily integrated into established diabetes education programs without a negative impact on diabetes care or delivery of diabetes education. However, an intervention of moderate intensity for smoking cessation was no more effective than usual care in assisting patients with tobacco cessation after 6-month follow-up. Whether a more intensive intervention, targeting patients expressing a readiness to discontinue tobacco use, and/or a longer duration or a more cumulative effect of treatment will be more effective must be evaluated.", "The purpose of this study was to evaluate the impact of a smoking cessation intervention for hospitalized patients, implemented by regular staff and incorporated into their routine care of patients.\n The intervention was conducted in one experimental hospital and in two control hospitals.\n One year after discharge, 15% of smokers became non-smokers in the experimental hospital versus 8% in the control hospitals. This difference is not statistically significant (p = 0.08), however a small sample in the control hospitals had an influence on the statistical power. A logistic regression highlights program participation as the only variable predictive of a non-smoker status one year after discharge, considering both types of hospitals (experimental and control).\n Establishing relevancy of smoking cessation intervention for hospitalized patients is probably no longer needed. But research should be carried on towards finding better ways to convince the staff to intervene, towards establishing relevancy for specialized staff and defining intensity of required interventions before and after hospitalization.", "We examined the ability of a provider-initiated, minimal-contact intervention to modify the smoking behavior of ambulatory clinic patients. Smokers at two outpatient sites were assigned to one of three groups: provider intervention only (PI); provider intervention plus self-help manual (PI/M); and usual care (control) group (C). The physician message emphasized the patient's personal susceptibility, the physician's concern, and the patient's ability to quit (self-efficacy). The nurse consultation concentrated on benefits and barriers associated with stopping, and on strategies for cessation. Telephone interviews were conducted with the 250 participants within a few days of their clinic visit and again at one and six months. Both PI and PI/M proved to be superior to usual care in motivating attempts to quit at both one-month and six-month follow-ups, and logistic regression analyses indicated that participants receiving the self-help manual in addition to the health provider message were between two and three times more likely to quit smoking during the study period than were participants in either of the other study groups.", "Family physicians (FPs) in Australia underutilize effective strategies to help patients stop smoking. We conducted a cluster randomization trial to evaluate a multifaceted, practice-based intervention involving audit, feedback, and academic detailing to improve FP smoking cessation advice.\n Sixty FPs in 39 practices participated. FPs' provision of smoking cessation advice was measured by patient recall, medical record audit, and FP self-report. Logistic regression analysis using generalized estimating equations was performed to assess improvements in practice, after adjustment for clustering by practice.\n Improvements between baseline and posttest in patient recall of FP advice about nicotine replacement patches and gum were significantly greater in the intervention than in the control group (P = 0.0056 and P = 0.0002, respectively). While there were substantial increases in patient recall of assessment of smoking status and FP use of \"quit dates,\" behavioral advice, and written materials in the intervention group, these changes were not significantly greater than those in the control group. Notation of patients' smoking status and smoking cessation advice in medical records remained suboptimal in both groups.\n This multifaceted intervention was successful only in promoting FPs' use of nicotine replacement therapy. While the use of other effective cessation strategies appeared to increase, a larger trial is needed for further evaluation.", "To measure the effect of behaviourally oriented counselling in general practice on healthy behaviour and biological risk factors in patients at increased risk of coronary heart disease.\n Cluster randomised controlled trial.\n 883 men and women selected for the presence of one or more modifiable risk factors: regular cigarette smoking, high serum cholesterol concentration (6.5-9.0 mmol/l), and high body mass index (25-35) combined with low physical activity.\n Brief behavioural counselling, on the basis of the stage of change model, carried out by practice nurses to reduce smoking and dietary fat intake and to increase regular physical activity.\n Questionnaire measures of diet, exercise, and smoking habits, and blood pressure, serum total cholesterol concentration, weight, body mass index, and smoking cessation (with biochemical validation) at 4 and 12 months.\n Favourable differences were recorded in the intervention group for dietary fat intake, regular exercise, and cigarettes smoked per day at 4 and 12 months. Systolic blood pressure was reduced to a greater extent in the intervention group at 4 but not at 12 months. No differences were found between groups in changes in total serum cholesterol concentration, weight, body mass index, diastolic pressure, or smoking cessation.\n Brief behavioural counselling by practice nurses led to improvements in healthy behaviour. More extended counselling to help patients sustain and build on behaviour changes may be required before differences in biological risk factors emerge.", "GPs are an important source of smoking cessation advice. This research examined whether a model encouraging GP referral of patients who smoke to a specialist service would be acceptable and effective for increased smoking cessation when compared with a model of in-practice management.\n The study design was cluster randomized controlled trial. Practices were randomized to one of two interventions, at a rate of 1:2: (i) standard in-practice GP management or (ii) referral to a quitline service. The main outcome measures were sustained abstinence of >or=1 month duration at 3-month follow-up and >or=10 months duration at 12 months, using intention to treat analysis.\n At 3-month follow-up, patients in the referral condition were twice as likely to report sustained abstinence than those in the in-practice condition [12.3% compared with 6.9%; odds ratio (OR) = 1.92 (95% confidence interval (CI) 1.17-3.13]. At 12-month follow-up, patients in the referral condition had nearly three times the odds of sustained abstinence [6.5% compared with 2.6%; OR = 2.86 (95% CI 0.94-8.71)]. The intervention effect was mediated by the amount of help received outside the practice.\n This research provided evidence that GPs referring smokers to an evidence-based quitline service results in increased cessation. The benefit is largely due to patients in the referral condition receiving more external help than patients in the in-practice condition, as they received equivalent practice-based help. Where suitable services exist, we recommend that referral become the normative strategy for management of smoking cessation in general practice to complement any practice-based help provided.", "Medical advice and use of nicotine gum have recently received increased attention as effective tools to encourage smokers to quit, yet the relative value of nurse vs physician counseling has not been explored in depth. In this study, 425 smokers attending three urban primary care centers in Barcelona were systematically allocated to one of three groups: group A patients received a brief counseling session to quit from their family physician; group B patients were given the same brief counseling along with a free supply of nicotine gum; group C received a brief health-education session from the primary care nurse. Three hundred forty-nine patients (82%) could be reached by telephone at the two-month follow up. By that time, after correcting for the estimated validity of the phone report of smoking status, the proportion declaring themselves to be nonsmokers was 10.9%, 11.1%, and 10.8%, respectively, without significant differences between them. At one-year follow up the proportions were 4.4%, 5.3%, and 6.0%. In the logistic regression analysis, only the expected difficulty of quitting was predictive of one-year abstention, OR = 3.1 (95% CI: 1.3-7.3). The present study shows no difference between physician versus nurse counseling and no improvement in the proportion of quitters with the addition of nicotine gum in the physician-counseled group.", "The primary care visit represents an important venue for intervening with a large population of smokers. However, physician adherence to the Smoking Cessation Clinical Guideline (5As) remains low. We evaluated the effectiveness of a computer-tailored intervention designed to increase smoking cessation counseling by primary care physicians.\n Physicians and their patients were randomized to either intervention or control conditions. In addition to brief smoking cessation training, intervention physicians and patients received a one-page report that characterized the patients' smoking habit and history and offered tailored recommendations. Physician performance of the 5As was assessed via patient exit interviews. Quit rates and smoking behaviors were assessed 6 months postintervention via patient phone interviews. Intervention effects were tested in a sample of 70 physicians and 518 of their patients. Results were analyzed via generalized and mixed linear modeling controlling for clustering.\n Intervention physicians exceeded controls on \"Assess\" (OR 5.06; 95% CI 3.22, 7.95), \"Advise\" (OR 2.79; 95% CI 1.70, 4.59), \"Assist-set goals\" (OR 4.31; 95% CI 2.59, 7.16), \"Assist-provide written materials\" (OR 5.14; 95% CI 2.60, 10.14), \"Assist-provide referral\" (OR 6.48; 95% CI 3.11, 13.49), \"Assist-discuss medication\" (OR 4.72;95% CI 2.90, 7.68), and \"Arrange\" (OR 8.14; 95% CI 3.98, 16.68), all p values being < 0.0001. Intervention patients were 1.77 (CI 0.94, 3.34,p = 0.078) times more likely than controls to be abstinent (12 versus 8%), a difference that approached, but did not reach statistical significance, and surpassed controls on number of days quit (18.4 versus 12.2, p < .05) but not on number of quit attempts.\n The use of a brief computer-tailored report improved physicians' implementation of the 5As and had a modest effect on patients' smoking behaviors 6 months postintervention.", "This study evaluated the effectiveness of three smoking cessation interventions for this population: (1) modified usual care (UC); (2) brief advice (A); and (3) brief advice plus more extended counseling during and after hospitalization (A + C).\n Smokers (2,095) who were in-patients in four hospitals were randomly assigned to condition. Smoking status was ascertained via phone interview 7 days and 12 months post-discharge. At 12 months, reports of abstinence were validated by analysis of saliva cotinine. Intent to treat analyses were performed.\n At 7-day follow-up, 24.2% of participants reported abstinence in the previous 7 days. There were no differences between conditions. At 12-month follow-up, self-reported abstinence was significantly higher in the A + C condition (UC (15.0%) vs. A (15.2%) vs. A + C (19.8%)). There was no significant difference among conditions in cotinine-validated abstinence, however (UC (8.8%) vs. A (10.0%) vs. A + C (9.9%)).\n These interventions for hospital in-patients did not increase abstinence rates. Features of the study that might have contributed to this finding were the inclusiveness of the participation criteria, the fact that pharmacological aids were not provided, and a stage-matching approach that resulted in less intensive counseling for participants unwilling to set a quit date.", "Few research studies have evaluated the effectiveness of smoking interventions in hospitalized patients. This randomized controlled trial compared the efficacy of 2 smoking cessation programs in patients hospitalized in 4 community hospitals in a large health maintenance organization within the San Francisco Bay Area in California.\n Patients were randomly assigned to usual care (n = 990), nurse-mediated, behaviorally oriented inpatient counseling focused on relapse prevention with 1 postdischarge telephone contact (minimal intervention, n = 473), or the same inpatient counseling with 4 postdischarge telephone contacts (intensive intervention, n = 561). The main outcome measure, smoking cessation rate, was corroborated by plasma cotinine determination or family confirmation, 1 year after enrollment.\n At 1 year smoking cessation rates were 27%, 22%, and 20% for intensive intervention, minimal intervention, and usual care groups, respectively (P = .009 for intensive vs usual care). Subgroup analyses by diagnosis revealed that the odds of cessation among patients with cardiovascular disease or other internal medical conditions were greater among those receiving the intensive intervention than among their counterparts receiving usual care (odds ratios, 1.6 and 2.0, respectively).\n A multicomponent smoking cessation program consisting of physician advice; in-hospital, nurse-mediated counseling; and multiple postdischarge telephone contacts was effective in increasing smoking cessation rates among hospitalized smokers. Hospital-wide smoking cessation programs could substantially increase the effectiveness of hospital smoking bans.", "Continued high rates of smoking among socioeconomically disadvantaged women lead to increases in children's health problems associated with exposure to tobacco smoke. The pediatric clinic is a \"teachable setting\" in which to provide advice and assistance to parents who smoke.\n To evaluate a smoking cessation intervention for women.\n Two-arm (usual care vs intervention) randomized trial.\n Pediatric clinics serving an ethnically diverse population of low-income families in the greater Seattle, Wash, area.\n During the clinic visit, women received a motivational message from the child's clinician, a guide to quitting smoking, and a 10-minute motivational interview with a nurse or study interventionist. Women received as many as 3 outreach telephone counseling calls from the clinic nurse or interventionist in the 3 months following the visit.\n Self-identified women smokers (n = 303) whose children received care at participating clinics.\n Self-reported abstinence from smoking 12 months after enrollment in the study, defined as not smoking, even a puff, during the 7 days prior to assessment.\n Response rates at 3 and 12 months were 80% and 81%. At both follow-ups, abstinence rates were twice as great in the intervention group as in the control group (7.7% vs 3.4% and 13.5% vs 6.9%, respectively). The 12-month difference was statistically significant.\n A pediatric clinic smoking cessation intervention has long-term effects in a socioeconomically disadvantaged sample of women smokers. The results encourage implementation of evidence-based clinical guidelines for smoking cessation in pediatric practice.", "Few studies have rigorously evaluated whether providing biologically based health-risk feedback is more effective than standard interventions in increasing smokers' motivation to quit and their long-term abstinence.\n An RCT was conducted from 2005 to 2008. Data were analyzed in 2008.\n Smokers (N=536) were recruited from the community, regardless of their interest in quitting smoking.\n Smokers either received brief ( approximately 20 minutes), personally tailored counseling sessions based on their lung functioning, carbon monoxide (CO) exposure, and smoking-related health conditions, or they received generic smoking-risk information and personalized counseling about their diet, BMI, and physical activity. All were advised to quit smoking and were offered access to a free phone-counseling program.\n Treatment utilization and abstinence at 6 and 12 months post-intervention.\n Participants who received the experimental treatment demonstrated no greater motivation to quit, use of treatment services, or abstinence compared to controls at either follow-up assessment. In fact, controls reported greater motivation to quit at 12 months (M 3.42 vs 3.20, p=0.03), greater use of pharmacotherapy at 6 months (37.8% vs 28.0%, p=0.02), and greater 30-day point prevalent abstinence at 6 months, after controlling for relevant covariates (10.8% vs 6.4%, adjusted p=0.04).\n The present study found no support for adding a personalized health-risk assessment emphasizing lung health and CO exposure to generic cessation advice and counseling for community-based smokers not otherwise seeking treatment.\n NCT00169260.", "Guidelines recommend that smoking cessation interventions are offered in all clinical settings to all smokers willing to make a quit attempt. Since the effectiveness of routine provision of behavioural counselling and nicotine replacement therapy (NRT) to smokers admitted to hospital has not been established, a randomised controlled trial of these interventions given together compared with counselling alone or minimal intervention was performed in hospital inpatients.\n Medical and surgical inpatients who were current smokers at the time of admission were randomised to receive either usual care (no additional advice at admission), counselling alone (20 minute intervention with written materials), or NRT plus counselling (counselling intervention with a 6 week course of NRT). Continuous and point prevalence abstinence from smoking (validated by exhaled carbon monoxide <10 ppm) was measured at discharge from hospital and at 3 and 12 months, and self-reported reduction in cigarette consumption in smokers was assessed at 3 and 12 months.\n 274 inpatient smokers were enrolled. Abstinence was higher in the NRT plus counselling group (n=91) than in the counselling alone (n=91) or usual care (n=92) groups. The difference between the groups was significant for validated point prevalence abstinence at discharge (55%, 43%, 37% respectively, p=0.045) and at 12 months (17%, 6%, 8%, p=0.03). The respective differences in continuous validated abstinence at 12 months were 11%, 4%, 8% (p=0.25). There was no significant difference between counselling alone and usual care, or in reduction in cigarette consumption between the treatment groups.\n NRT given with brief counselling to hospital inpatients is an effective routine smoking cessation intervention.", "To test the effectiveness of a low-intensity intervention program for smoking cessation targeting the worksite environment in employees who had a low readiness to quit, we conducted an intervention trial at six intervention and six control worksites in Japan. A total of 2,307 smokers at baseline who remained at their worksite throughout the three-year study period were analyzed (1,017 in intervention and 1,290 in control groups). The multi-component program at the worksites consisted of (1) presenting information on the harms of tobacco smoking and the benefits of cessation by posters, websites, and newsletters; (2) smoking cessation campaigns for smokers; (3) advice on designation of smoking areas; and (4) periodic site-visits of the designated smoking areas by an expert researcher. At baseline, the intervention and control groups each had high prevalence of immotive or precontemplation, that reflected low readiness to quit (71.5% and 73.2%, respectively). The smoking cessation rate, as not having smoked for the preceding six months or longer, assessed at 36 months after the baseline survey by a self-administered questionnaire was significantly higher in the intervention group than the control group (12.1%, vs. 9.4%, p=0.021). The intervention program still had a significant effect on the smoking cessation rate after multiple logistic regression analysis adjusted for sex, age, type of occupation, age of starting smoking, quit attempts in the past, number of cigarettes per day, and readiness to quit (odds ratio: 1.38, 95% confidence interval: 1.05-1.81, p=0.02). The cost per additional quitter due to the intervention was calculated to be Yen 70,080. These findings indicate that this program is effective and can be implemented in similar workplaces where the prevalence of smoking is high and smokers' readiness to cease smoking is low.", "The objective was to assess the effectiveness of a directly mailed smoking cessation intervention to discharged hospital patients.\n A randomized controlled trial was used. In the 2 weeks after discharge, smokers in the intervention group were sent by mail a personally addressed letter from their medical consultant urging them to quit plus a self-help quitting manual, and smokers in the control group received usual care. Patients were surveyed about their smoking status at 6 and 12 months after discharge. A total of 1858 discharged patients responded to both questionnaires. The main outcome measures were self-reported smoking in past week at 6 and 12 months after discharge. Quitters at 12 months were biochemically tested for evidence of smoking.\n The results failed to show that smoking cessation advice directly mailed to a broad cross-section of discharged hospital patients who smoke led to smoking cessation. However, the intervention increased cessation among smokers with medical conditions for which quitting is highly relevant. In general, patients who were more likely to quit were older, had entered the hospital as an emergency case, and had a medical diagnosis for which quitting is highly relevant.\n This study suggests that hospital patients who smoke and are also diagnosed with conditions which call for quitting are more likely to quit if they receive from their consultant a personalized letter advising them to quit and a self-help manual.\n Copyright 1999 American Health Foundation and Academic Press.", "To determine if mothers receiving a smoking cessation intervention emphasizing health risks of environmental tobacco smoke (ETS) for their children have a higher quit rate than 1) mothers receiving routine smoking cessation advice or 2) a control group.\n Randomized, controlled trial.\n Primary care center in a large urban children's hospital.\n Four hundred seventy-nine mothers were randomly assigned to a smoking cessation intervention either aimed at their child's health or their own health, or to a control group receiving safety information.\n Smoking status, stage of change, cigarettes/day, location smoking occurred, and knowledge of ETS effects.\n Complete data (baseline and both follow-ups) were available for 166 subjects. There was no impact of group assignment on the quit rate, cigarettes/day, or stage of change. The Child Health Group intervention had a sustained effect on location where smoking reportedly occurred (usually outside) and on improved knowledge of ETS effects.\n Further research is needed to devise more effective methods of using the pediatric health care setting to influence adult smoking behaviors.", "Initial trials of web-based smoking-cessation programs have generally been promising. The active components of these programs, however, are not well understood. This study aimed to (1) identify active psychosocial and communication components of a web-based smoking-cessation intervention and (2) examine the impact of increasing the tailoring depth on smoking cessation.\n Randomized fractional factorial design.\n Two HMOs: Group Health in Washington State and Henry Ford Health System in Michigan.\n 1866 smokers.\n A web-based smoking-cessation program plus nicotine patch. Five components of the intervention were randomized using a fractional factorial design: high- versus low-depth tailored success story, outcome expectation, and efficacy expectation messages; high- versus low-personalized source; and multiple versus single exposure to the intervention components.\n Primary outcome was 7 day point-prevalence abstinence at the 6-month follow-up.\n Abstinence was most influenced by high-depth tailored success stories and a high-personalized message source. The cumulative assignment of the three tailoring depth factors also resulted in increasing the rates of 6-month cessation, demonstrating an effect of tailoring depth.\n The study identified relevant components of smoking-cessation interventions that should be generalizable to other cessation interventions. The study also demonstrated the importance of higher-depth tailoring in smoking-cessation programs. Finally, the use of a novel fractional factorial design allowed efficient examination of the study aims. The rapidly changing interfaces, software, and capabilities of eHealth are likely to require such dynamic experimental approaches to intervention discovery." ]	The results indicate the potential benefits of smoking cessation advice and/or counselling given by nurses to patients, with reasonable evidence that intervention is effective. The evidence of an effect is weaker when interventions are brief and are provided by nurses whose main role is not health promotion or smoking cessation. The challenge will be to incorporate smoking behaviour monitoring and smoking cessation interventions as part of standard practice, so that all patients are given an opportunity to be asked about their tobacco use and to be given advice and/or counselling to quit along with reinforcement and follow up.
CD006611	[ "21371991", "21722952", "15937529", "16046689" ]	[ "A theory-based video messaging mobile phone intervention for smoking cessation: randomized controlled trial.", "Smoking cessation support delivered via mobile phone text messaging (txt2stop): a single-blind, randomised trial.", "Smoking cessation using mobile phone text messaging is as effective in Maori as non-Maori.", "Do u smoke after txt? Results of a randomised trial of smoking cessation using mobile phone text messaging." ]	[ "Advances in technology allowed the development of a novel smoking cessation program delivered by video messages sent to mobile phones. This social cognitive theory-based intervention (called \"STUB IT\") used observational learning via short video diary messages from role models going through the quitting process to teach behavioral change techniques.\n The objective of our study was to assess the effectiveness of a multimedia mobile phone intervention for smoking cessation.\n A randomized controlled trial was conducted with 6-month follow-up. Participants had to be 16 years of age or over, be current daily smokers, be ready to quit, and have a video message-capable phone. Recruitment targeted younger adults predominantly through radio and online advertising. Registration and data collection were completed online, prompted by text messages. The intervention group received an automated package of video and text messages over 6 months that was tailored to self-selected quit date, role model, and timing of messages. Extra messages were available on demand to beat cravings and address lapses. The control group also set a quit date and received a general health video message sent to their phone every 2 weeks.\n The target sample size was not achieved due to difficulty recruiting young adult quitters. Of the 226 randomized participants, 47% (107/226) were female and 24% (54/226) were Maori (indigenous population of New Zealand). Their mean age was 27 years (SD 8.7), and there was a high level of nicotine addiction. Continuous abstinence at 6 months was 26.4% (29/110) in the intervention group and 27.6% (32/116) in the control group (P = .8). Feedback from participants indicated that the support provided by the video role models was important and appreciated.\n This study was not able to demonstrate a statistically significant effect of the complex video messaging mobile phone intervention compared with simple general health video messages via mobile phone. However, there was sufficient positive feedback about the ease of use of this novel intervention, and the support obtained by observing the role model video messages, to warrant further investigation.\n Australian New Zealand Clinical Trials Registry Number: ACTRN12606000476538; http://www.anzctr.org.au/trial_view.aspx?ID=81688 (Archived by WebCite at http://www.webcitation.org/5umMU4sZi).", "Smoking cessation programmes delivered via mobile phone text messaging show increases in self-reported quitting in the short term. We assessed the effect of an automated smoking cessation programme delivered via mobile phone text messaging on continuous abstinence, which was biochemically verified at 6 months.\n In this single-blind, randomised trial, undertaken in the UK, smokers willing to make a quit attempt were randomly allocated, using an independent telephone randomisation system, to a mobile phone text messaging smoking cessation programme (txt2stop), comprising motivational messages and behavioural-change support, or to a control group that received text messages unrelated to quitting. The system automatically generated intervention or control group texts according to the allocation. Outcome assessors were masked to treatment allocation. The primary outcome was self-reported continuous smoking abstinence, biochemically verified at 6 months. All analyses were by intention to treat. This study is registered, number ISRCTN 80978588.\n We assessed 11,914 participants for eligibility. 5800 participants were randomised, of whom 2915 smokers were allocated to the txt2stop intervention and 2885 were allocated to the control group; eight were excluded because they were randomised more than once. Primary outcome data were available for 5524 (95%) participants. Biochemically verified continuous abstinence at 6 months was significantly increased in the txt2stop group (10·7% txt2stop vs 4·9% control, relative risk [RR] 2·20, 95% CI 1·80-2·68; p<0·0001). Similar results were obtained when participants that were lost to follow-up were treated as smokers (268 [9%] of 2911 txt2stop vs 124 [4%] of 2881 control [RR 2·14, 95% CI 1·74-2·63; p<0·0001]), and when they were excluded (268 [10%] of 2735 txt2stop vs 124 [4%] of 2789 control [2·20, 1·79-2·71; p<0·0001]). No significant heterogeneity was shown in any of the prespecified subgroups.\n The txt2stop smoking cessation programme significantly improved smoking cessation rates at 6 months and should be considered for inclusion in smoking cessation services.\n UK Medical Research Council, Primary Care Research Networks.\n Copyright © 2011 Elsevier Ltd. All rights reserved.", "To determine whether a smoking cessation service using mobile phone text messaging is as effective for Maori as non-Maori.\n A single-blind randomised controlled trial was undertaken with recruitment targeted to maximise the participation of young Maori. The intervention included regular, personalised text messages providing smoking cessation advice, support, and distraction. Maori text messages related to Maori language, support messages (in Maori and English) and information on Maori traditions. Text messaging was free for 1 month. After 6 weeks, the number of messages reduced from 5 per day to 3 per week until the 26-week follow-up.\n Participants included 355 Maori and 1350 non-Maori. Maori in the intervention group were more likely to report quitting (no smoking in the past week) at 6 weeks (26.1%) than those in the control group (11.2%) RR 2.34, 95% CI: 1.44-3.79. There was no significant difference between the RR for Maori and that for non-Maori (RR: 2.16, 95%CI: 1.72-2.71).\n A mobile phone-based cessation programme was successful in recruiting young Maori, and was shown to be as effective for Maori as non-Maori at increasing short-term self-reported quit rates. This shows clear potential as a new public health initiative.", "To determine the effectiveness of a mobile phone text messaging smoking cessation programme.\n Randomised controlled trial\n New Zealand\n 1705 smokers from throughout New Zealand who wanted to quit, were aged over 15 years, and owned a mobile phone were randomised to an intervention group that received regular, personalised text messages providing smoking cessation advice, support, and distraction, or to a control group. All participants received a free month of text messaging; starting for the intervention group on their quit day to assist with quitting, and starting for the control group at six months to encourage follow up. Follow up data were available for 1624 (95%) at six weeks and 1265 (74%) at six months.\n The main trial outcome was current non-smoking (that is, not smoking in the past week) six weeks after randomisation. Secondary outcomes included current non-smoking at 12 and 26 weeks.\n More participants had quit at six weeks in the intervention compared to the control group: 239 (28%) v 109 (13%), relative risk 2.20 (95% confidence interval 1.79 to 2.70), p < 0.0001. This treatment effect was consistent across subgroups defined by age, sex, income level, or geographic location (p homogeneity > 0.2). The relative risk estimates were similar in sensitivity analyses adjusting for missing data and salivary cotinine verification tests. Reported quit rates remained high at six months, but there was some uncertainty about between group differences because of incomplete follow up.\n This programme offers potential for a new way to help young smokers to quit, being affordable, personalised, age appropriate, and not location dependent. Future research should test these findings in different settings, and provide further assessment of long term quit rates." ]	The current evidence shows a benefit of mobile phone-based smoking cessation interventions on long-term outcomes, though results were heterogenous with findings from three of five included studies crossing the line of no effect. The studies included were predominantly of text messaging interventions. More research is required into other forms of mobile phone-based interventions for smoking cessation, other contexts such as low income countries, and cost-effectiveness.
CD000507	[ "375178", "7472106", "8517902", "3312553", "3794867", "9329410" ]	[ "Effect of heparinization of fluids infused through an umbilical artery catheter on catheter patency and frequency of complications.", "Prevention of umbilical artery catheter clots with heparinized infusates.", "Effect of adding heparin in very low concentration to the infusate to prolong the patency of umbilical artery catheters.", "Effect of heparin infusates in umbilical arterial catheters on frequency of thrombotic complications.", "Efficacy of thromboresistant umbilical artery catheters in reducing aortic thrombosis and related complications.", "Heparin and the risk of intraventricular hemorrhage in premature infants." ]	[ "Heparinization of fluids (1 unit/ml) infused through an umbilical artery catheter (UAC) was efficacious in prolonging catheter patency in a double-blind, randomized, controlled clinical study. On the basis of life-table analysis, the half-life of catheter function was seven days in the heparinized group as compared with just over two days in the nonheparinized group (P less than .01). UAC occlusion occurred in 4 of 32 patients in the heparinized and 19 of 30 in the nonheparinized group (chi 2 = 17.6, P less than .01). Blood transfusions, number of arterial blood gases drawn through the UACs, and fluid infusion rates were not related to catheter occlusion. Heparinization of the UAC infusion did not alter the partial thromboplastin time or the incidence of catheter-related thromboembolic phenomena in the extremities. Heparinization of fluids infused through a UAC appears to be useful in the care of critically ill neonates.", "49 neonates requiring umbilical artery catheters (UACs) were randomly assigned to receive standard or heparin-containing infusates. 3 of 23 (13%) of the patients receiving heparin had catheters removed because they became functionally occluded compared to 15 of 26 (58%) in the control group (p less than 0.005). 4 of 13 (31%) single injection aortograms obtained in control infants demonstrated thrombi, compared to none of 7 in the heparin group. 1 patient in the heparin group had an aortic clot demonstrated at post-mortum examination. There were neither clinical coagulopathies nor abnormalities of partial thromboplastin time attributable to the administration of heparinized fluids. Heparinization of UAC infusates appears to be a safe method of reducing the risk of catheter occlusion. Heparin effect on large vessel clot risk remains unproven.", "A randomized controlled study was done to determine whether the addition of heparin, in very low concentration (0.25 U/ml), to fluids administered through an umbilical artery catheter (UAC) would affect the duration of catheter patency. UAC occlusion occurred in 2 of 15 patients in the heparin group and in 11 of 15 patients in the control group (p = 0.001). Using life-table analysis, the functional life span of UAC was estimated. On day 8, 100% of UACs in heparin group and 9% of UACs in control group were patent (p < 0.05). Coagulation profile remained unaltered after addition of heparin compared with that before the start of the therapy. There was no difference in the incidence of subependymal intraventricular hemorrhage between the two groups. It is concluded that heparin in such low concentration is effective in prolonging duration of UAC patency without causing adverse effects.", "We studied 111 infants requiring an umbilical artery catheter, 59 with heparin and 52 without. Thirty-four thrombi were detected, 16 in the heparin group and 18 in the control group. The numbers of thrombi in the two groups was not significantly different, but the number of clotted or nonfunctioning umbilical artery catheters was greater in the control group (P less than 0.05), as was the incidence of hypertension (P less than 0.05). There were no other significant differences between the two groups. We conclude that the use of low doses of heparin may not change the incidence of umbilical artery catheter-related thrombi, but it does appear to lower the incidence of their sequelae.", "Previous in vitro and in vivo reports suggest that catheters constructed of polyurethane with heparin bonded to the surface (HB-PU) are less thrombogenic than catheters made of polyvinyl chloride (PVC). A randomized trial sufficiently large (power 80%) to detect a reduction in the incidence of umbilical artery (UA) catheter complications, including aortic thrombus formation, from 45% to 20% was conducted in 125 infants. The infants were monitored for complications possibly related to the use of a UA catheter, such as systemic hypertension and abnormalities of lower extremity perfusion. The presence of aortic thrombi was assessed by ultrasound study 3.5 +/- 1.2 (SD) days and 11.1 +/- 2.3 days after insertion of the catheter. The use of HB-PU umbilical catheters did not lead to a significant reduction in the incidence of complications and aortic thrombi compared with the use of PVC catheters. The lack of reduction may have been related to the prolonged duration of catheter use in both groups. A much larger study would have been required to detect a smaller, but perhaps clinically significant, reduction in catheter-associated complications.", "This study was carried out to determine whether the routine use of low-dose heparin in umbilical catheter infusates increases the risk of intraventricular hemorrhage or alters the coagulation profile in premature infants.\n In a randomized, blinded trial, 113 infants born at less than 31 weeks' gestation were assigned to receive, in their umbilical catheter infusate, either 1 unit of heparin per milliliter (n = 55) or no heparin (n = 58). Prothrombin time, activated partial thromboplastin time, fibrinogen concentration, and antithrombin III activity levels were determined at the start and the completion of the study. Cranial ultrasonography was performed during the first week of life.\n There was no difference in the incidence of intraventricular hemorrhage between the heparin and no heparin groups, 35.8% and 31.5%, respectively (p = 0.6). Similarly, no difference was detected in the incidence of severe intraventricular hemorrhage (grades III/IV). Prothrombin time, activated partial thromboplastin time, and fibrinogen levels were not significantly different between the two groups. However, the use of heparin was associated with a lower antithrombin III activity level. Antenatal indomethacin use was associated with a 2.9 increased risk of intraventricular hemorrhage (95% confidence interval, 1.15 to 7.17).\n A low dose of heparin added to umbilical catheter infusates does not increase the incidence or severity of intraventricular hemorrhage or significantly alter the coagulation profile in premature infants." ]	Heparinization of the fluid infused through an umbilical arterial catheter decreases the likelihood of umbilical arterial catheters occluding. The lowest concentration tested so far (0.25 units/mL) has been shown to be effective. Heparinization of flushes without heparinizing the infusate is ineffective. The frequency of aortic thrombosis has not been shown to be affected; however, the confidence intervals for this effect are very wide. The frequency of intraventricular hemorrhage has not been shown to be affected by heparinization of the infusate, but again the confidence intervals are very wide and even a major increase in the incidence of grade 3 and 4 intraventricular hemorrhage would not have been detected.
CD006856	[ "1415030" ]	[ "An advocacy intervention program for women with abusive partners: initial evaluation." ]	[ "Experimentally tested the hypotheses that (1) battered women are in need of numerous community resources upon exit from a domestic violence shelter, (2) working with advocates increases women's effectiveness in obtaining needed resources and social support, and (3) success in obtaining resources and social support increases women's levels of life satisfaction and decreases their risk of further abuse. The initial findings of a short-term intervention project designed to provide postshelter advocacy services to women with abusive partners are presented. One-hundred forty-one battered women were interviewed immediately upon their exit from a domestic violence shelter as well as 10 weeks thereafter. Half the sample was randomly assigned to receive the services of trained advocates who assisted them in accessing needed community resources. Women who worked with advocates reported being more effective in accessing resources and had higher levels of social support and overall quality of life postintervention. Although all women reported some decrease in postshelter abuse, there were no differences between those with and those without advocates, and abuse continued to be a problem for many women." ]	Research in this field is limited. When implementing new programmes, recipients could be randomly assigned to different forms of assistance. While advocates may support personal assistance for myriad reasons, this review demonstrates that further studies are required to determine which models of personal assistance are most effective and efficient for particular people.
CD005108	[ "16281998", "17325405", "12764513", "10413387", "9637578", "18552625", "3303097", "12402370", "12570118", "8541826", "19675115", "15788528", "14695367", "9619472", "11157015" ]	[ "Randomised controlled trial of a lay-led self-management programme for Bangladeshi patients with chronic disease.", "The effectiveness and cost effectiveness of a national lay-led self care support programme for patients with long-term conditions: a pragmatic randomised controlled trial.", "Implementation and quantitative evaluation of chronic disease self-management programme in Shanghai, China: randomized controlled trial.", "Evidence suggesting that a chronic disease self-management program can improve health status while reducing hospitalization: a randomized trial.", "Pilot randomized trial of education to improve self-management skills of men with symptomatic HIV/AIDS.", "Clinical trial of wellness training: health promotion for severely mentally ill adults.", "Influence of aerobic exercise training and relaxation training on physical and psychologic health following stressful life events.", "Medication and symptom management education program for the rehabilitation of psychiatric patients in Korea: the effects of promoting schedule on self-efficacy theory.", "Evaluation of an individualised asthma programme directed at behavioural change.", "The effects of a cognitive behavioural intervention in asthmatic patients.", "Effectiveness of a video-based exercise programme to reduce falls and improve health-related quality of life among older adults discharged from hospital: a pilot randomized controlled trial.", "Improving physical fitness and emotional well-being in adolescents of low socioeconomic status in Chile: results of a school-based controlled trial.", "What picture is worth a thousand words? A comparative evaluation of a burn prevention programme by type of medium in Israel.", "Psychological and cognitive outcomes of a randomized trial of exercise among patients with chronic obstructive pulmonary disease.", "Structured exercise improves physical functioning in women with stages I and II breast cancer: results of a randomized controlled trial." ]	[ "Reducing the impact of chronic disease in minority ethnic groups is an important public health challenge. Lay-led education may overcome cultural and language barriers that limit the effectiveness of professionally-led programmes. We report the first randomised trial of a lay-led self-management programme - the Chronic Disease Self-Management Programme (CDSMP) (Expert Patient Programme) - in a south Asian group.\n To determine the effectiveness of a culturally-adapted lay-led self-management programme for Bangladeshi adults with chronic disease.\n Randomised controlled trial.\n Tower Hamlets, east London.\n We recruited Bangladeshi adults with diabetes, cardiovascular disease, respiratory disease or arthritis from general practices and randomised them to the CDSMP or waiting-list control. Self-efficacy (primary outcome), self-management behaviour, communication with clinician, depression scores, and healthcare use were assessed by blinded interviewer-administered questionnaires in Sylheti before randomisation and 4 months later.\n Of the 1363 people invited, 476 (34%) agreed to take part and 92% (439/476) of participants were followed up. The programme improved self-efficacy (difference: 0.67, 95% confidence interval [CI] = 0.08 to 1.25) and self-management behaviour (0.53; 95% CI = 0.01 to 1.06). In the 51% (121/238) of intervention participants attending three or more of the 6-weekly education sessions the programme led to greater improvements in self-efficacy (1.47; 95% CI = 0.50 to 1.82) and self-management behaviour (1.16; 95% CI = 0.50 to 1.82), and reduced HADS depression scores (0.64; 95% CI = 0.07 to 1.22). Communication and healthcare use were not significantly different between groups. The programme cost pound123 (181) per participant.\n A culturally-adapted CDSMP improves self-efficacy and self-care behaviour in Bangladeshi patients with chronic disease. Effects on health status were marginal. Benefits were limited by moderate uptake and attendance.", "Supporting patients' self care could have a major effect on the management of long-term conditions, which has led to worldwide interest in effective self care interventions. In England, self care support is being developed through the \"Expert Patients Programme\", which provides lay-led generic courses to improve patients' self care skills. However, the clinical and cost effectiveness of such courses remains unclear.\n Two-arm pragmatic randomised controlled trial design with waiting list control in community settings in England. 629 patients with a wide range of self-defined long-term conditions were studied. The lay-led self care support group involved 6-weekly sessions to teach self care skills. Primary outcomes were self-efficacy, reported energy and routine health services utilisation at 6 months. A cost-effectiveness analysis was also conducted.\n Patients receiving immediate course access reported considerably greater self-efficacy and energy at 6-month follow-up, but reported no statistically significant reductions in routine health services utilisation over the same time period. The cost-effectiveness analysis showed that patients receiving immediate course access reported considerably greater health related quality of life, and a small reduction in costs. If a quality adjusted life year was valued at 20,000 pounds (39,191 dollars; 30,282 Euro), there was a 70% probability that the intervention was cost effective.\n Lay-led self care support groups are effective in improving self-efficacy and energy levels among patients with long-term conditions, and are likely to be cost effective over 6 months at conventional values of a decision-maker's willingness to pay. They may be a useful addition to current services in the management of long-term conditions.", "To evaluate the effectiveness of the Shanghai Chronic Disease Self-Management Program (CDSMP).\n A randomized controlled trial with six-month follow-up compared patients who received treatment with those who did not receive treatment (waiting-list controls) in five urban communities in Shanghai, China. Participants in the treatment group received education from a lay-led CDSMP course and one copy of a help book immediately; those in the control group received the same education and book six months later.\n In total, 954 volunteer patients with a medical record that confirmed a diagnosis of hypertension, heart disease, chronic lung disease, arthritis, stroke, or diabetes who lived in communities were assigned randomly to treatment (n = 526) and control (n = 428) groups. Overall, 430 (81.7%) and 349 (81.5%) patients in the treatment and control groups completed the six-month study. Patients who received treatment had significant improvements in weekly minutes of aerobic exercise, practice of cognitive symptom management, self-efficacy to manage own symptoms, and self-efficacy to manage own disease in general compared with controls. They also had significant improvements in eight indices of health status and, on average, fewer hospitalizations.\n When implemented in Shanghai, the CDSMP was acceptable culturally to Chinese patients. The programme improved participants' health behaviour, self-efficacy, and health status and reduced the number of hospitalizations six months after the course. The locally based delivery model was integrated into the routine of community government organizations and community health services. Chinese lay leaders taught the CDSMP courses as successfully as professionals.", "This study evaluated the effectiveness (changes in health behaviors, health status, and health service utilization) of a self-management program for chronic disease designed for use with a heterogeneous group of chronic disease patients. It also explored the differential effectiveness of the intervention for subjects with specific diseases and comorbidities.\n The study was a six-month randomized, controlled trial at community-based sites comparing treatment subjects with wait-list control subjects. Participants were 952 patients 40 years of age or older with a physician-confirmed diagnosis of heart disease, lung disease, stroke, or arthritis. Health behaviors, health status, and health service utilization, as determined by mailed, self-administered questionnaires, were measured.\n Treatment subjects, when compared with control subjects, demonstrated improvements at 6 months in weekly minutes of exercise, frequency of cognitive symptom management, communication with physicians, self-reported health, health distress, fatigue, disability, and social/role activities limitations. They also had fewer hospitalizations and days in the hospital. No differences were found in pain/physical discomfort, shortness of breath, or psychological well-being.\n An intervention designed specifically to meet the needs of a heterogeneous group of chronic disease patients, including those with comorbid conditions, was feasible and beneficial beyond usual care in terms of improved health behaviors and health status. It also resulted in fewer hospitalizations and days of hospitalization.", "To evaluate the acceptability, practicality, and short-term efficacy of a health education program to improve disease self-management in patients with symptomatic HIV/AIDS.\n Randomized controlled trial, baseline and 3-month follow-up questionnaire assessments.\n San Francisco Bay communities.\n Seventy-one men with symptomatic HIV or AIDS were randomly assigned to a seven-session group educational intervention (N=34) or a usual-care control group (N=37).\n Interactive health education groups were used to teach wide-ranging disease self-management skills and information: symptom assessment and management, medication use, physical exercise, relaxation, doctor-patient communication, and nutrition. Each group was led by two trained peer-leaders (one of whom was HIV-positive) recruited from the community.\n The primary outcome of interest was symptom status. Secondary outcomes were self-efficacy and health behaviors. Analysis of covariance was used to compare experimental and control group mean outcomes, adjusting for baseline value differences.\n The symptom severity index (number of symptoms moderate or greater severity) decreased in the experimental, and increased in the control group (-0.9 versus +0.5; p < .03). Pain, fatigue, and psychological symptoms were not significantly different between groups. Self-efficacy for controlling symptoms improved in the experimental, and decreased in the control group (+4 versus -7; p < .02). Changes in stress/relaxation exercises and HIV/AIDS knowledge were not different between groups. A trend was shown toward more frequent physical exercise in the experimental group compared with less in the control group (+1.3 versus -0.5 times/week; p=.06).\n Health education emphasizing self-management skills for HIV/AIDS patients can be implemented and evaluated and was accepted by patients, peer-leaders, and health care providers. Whether this educational program can lead to prolonged improvement in HIV symptoms and behaviors can be adequately addressed only by a larger trial of longer duration.", "This randomized controlled trial examined benefits of adding active health promotion to basic primary care (BPC) services for SMI adults. It compared BPC with BPC plus wellness training (WT), a 12 months intervention promoting individual skills in self-management. Three hundred nine participants enrolled during short-term residential treatment completed baseline assessments and were assigned to treatment groups, before discharge. Outcomes of perceived health status (SF-36), global assessment of function, and ratings of self-efficacy were assessed at follow-up interviews at 6, 12, and 18 months. The intent-to-treat analysis employed multilevel regression to examine differences by group on outcomes across time, controlling for health related covariates. The WT group showed significantly better outcomes on the SF-36 physical functioning and general health scales. Findings affirm ability of SMI adults to benefit from active health promotion.", "An experiment was conducted to determine whether aerobic exercise training or relaxation training would be effective for reducing the deleterious effects of life stress on physical and psychologic health. Over 1000 college students were surveyed, and 55 of those who reported experiencing a high number of negative life events over the preceding year were assigned to an aerobic exercise training condition, a relaxation training condition, or a no-treatment control condition. Physical and psychologic health were assessed with self-report measures before, halfway through, immediately following, and 8 weeks after the 11-week training (and control) period. Heart rate data collected during a treadmill test indicated that the aerobic exercise training was effective for improving cardiovascular fitness. Psychologic measures indicated that the exercise training condition was more effective than the other two conditions for reducing depression during the first 5 weeks of training. No differences were found among the conditions on self-report measures of physical health. These findings suggest that aerobic exercise training may be useful for reducing the severity and duration of depressive reactions following stressful life change.", "An effective rehabilitation program was developed for psychiatric patients' self-management of medication and symptoms. The rehabilitation program was designed to allow the patients to understand their illness, cope with their medical regimen, and prevent a relapse by recognizing any of the symptoms when they recur. This study consisted of three phases. The first phase was to explore the extent and the specific mental health needs of psychiatric patients. Data was obtained from 82 subjects who had symptoms of a mental illness including schizophrenia, bipolar disorders, and delusional disorder. They had received medication instruction during their hospitalization. The subjects were at the time outpatients in a psychiatric hospital. In the second phase, the researchers developed an educational program focused on coping with the residual and relapse warning signs, managing the drug side effects, medication compliance, and daily routines, according to the information acquired in the first step. The developed program includes the self-efficacy method reported by Bandura, including manuals and videotapes focusing on real life situations, small group discussions, and telephone coaching. Finally, the researchers investigated the effects of this program. Thirty-eight patients were selected for this study, 18 in the experimental program and 20 as controls. The diagnoses were same as those with the first step. The results showed that the subjects who attended this educational program reported significantly more improvement in self-efficacy (p=0.014) and medication compliance (p= 0.005), and significantly less relapse warning symptom scores (p=0.000) than the controls. In conclusion, these instructional materials will be beneficial for medication and symptom management in rehabilitating psychiatric patients in Korea. In addition, the materials may be a useful psychoeducational resource for professionals in the field of clinical psychiatry.", "An individualised asthma programme directed at behavioural change was evaluated in asthmatic subjects who reported complaints and impairment, despite adequate medical treatment. Mild-to-moderate asthma patients (n=23) were randomly assigned to a programme or waiting list condition. Outcome measures were: McMaster Asthma Quality of Life Questionnaire, Asthma Symptom Checklist, Negative Emotionality Scale, Knowledge, Attitude and Self-Efficacy Asthma Questionnaire, Adherence Scale, and peak flow measurements. Both groups were evaluated at three consecutive moments, each separated by 3 months; the programme was delivered between the first two evaluations. At onset the patient received a workbook containing information, exercises and homework assignments. Psycho-education, behavioural and cognitive techniques were introduced during six 1-h individual sessions. Compared with controls the programme group reported less symptoms (obstruction, fatigue), better quality of life (activity, symptoms, emotions), decreased negative affectivity, and increased adherence, immediately after finishing the programme and at 3 months follow-up. All three cognitive variables (knowledge, attitude towards asthma, self-efficacy) and day and night peak flow ratings improved in the programme group but not in the waiting list group. Participation in an individualised programme resulted in improvement of asthma morbidity, and asthma-related behaviour and cognitions, in subjects reporting symptoms and impairment despite adequate medical therapy.", "There is evidence that educational programmes may improve patient's compliance with asthma treatment and control symptoms. Whilst medical parameters have been thoroughly studied, few data are available concerning psychological intervention. The aim of our open pilot study was to verify whether any difference in perceived illness and response style to asthma existed in the patients enrolled in an Asthma Rehabilitation Group (ARG) and in a Control Group (CG). Forty consecutive asthmatics were randomly enrolled, all of whom were diagnosed, treated and followed-up according to the International Guidelines. Both groups underwent a psychological assessment at baseline and after one year. A battery of questionnaires was used to obtain data relating to baseline characteristics (anxiety, depression, psychophysiological disorders), emotional reactions to asthma attacks (panic-fear, etc,) and cognitive variables (external control, psychological stigma, internal beliefs, external chance, etc.) involved in the perceived illness. In addition, the Asthma Rehabilitation Group patients underwent an educational programme and a cognitive-behavioural intervention. In both groups, a reduction of anxiety and depression scores was observed, as well as a significant improvement of the medical parameters evaluated. Only the Asthma Rehabilitation Group reported lower scores on the Psychophysiological Questionnaire and on the External Control Subscale after 1 year. The Control Group reported higher score on the External Chance Scale. The data of our study seem to confirm the effectiveness of psychological intervention on the cognitive skills involved in the perception and management of asthma. Larger scale studies on this topic are suggested.", "Falls, loss of health-related quality of life and physical capacity, reduced participation in activities of daily living, and increased fear of falling are all potential outcomes for older adults discharged from hospital. A low-cost video based exercise programme may address this.\n This study was a randomized controlled trial with blinded outcomes assessment and a six-month follow-up.\n Participants were older adults (>65 years) using a mobility aid discharged from a tertiary hospital in Brisbane, Australia, without referral for community-based rehabilitation services.\n A digital video disk-based programme encompassing six exercise types each with six levels of difficulty. A home visit from a project physiotherapist was conducted to ensure patient safety. Control group patients received usual care.\n Falls, health-related quality of life, participation in activities of daily living, physical capacity and fear of falling.\n Study participants (n = 53, 19 intervention, 34 control) experienced decreasing health-related quality of life, several falls (72), and lower levels of participation in activities of daily living over the six-month follow-up. The intervention group did not differ significantly from the control group in terms of the outcomes examined, though a non-significant reduction in the rate of falls was observed. Intervention group participants complied with the exercise programme well during the first two weeks following discharge from hospital but then reduced their compliance levels thereafter.\n The intervention may be beneficial for reducing the rate of falls in this patient population though further research with a larger sample size is indicated.", "Regular physical activity is associated with a reduced risk of all-cause mortality, and mortality due to cardiovascular disease and cancer. Among adolescents, physical activity is associated with benefits in the prevention and control of emotional distress, and improvement of self-esteem. Countries in transitional epidemiological scenarios, such as Chile, need to develop effective strategies to improve physical activity as a way to face the epidemic of chronic diseases. The objective of this study was to evaluate the effects of a school-based physical activity program on physical fitness and mental health status of adolescents living in a low socioeconomic status area in Santiago, Chile. A quasi-experimental design was used to evaluate the effects of the program over one academic year. The study included 198 students aged 15 years old. Two ninth grade classes were randomly selected as the intervention group, with two classes of the same grade as controls. A social planning approach was used to develop the intervention. The program was designed and implemented based on student preferences, teachers' expertise and local resources. Changes in physiological and mental health status were assessed. After the intervention, maximum oxygen capacity achieved a significant increase of 8.5% in the intervention versus 1.8% in the control group (p < 0.0001). Speed and jump performance scores improved significantly more in the intervention versus the control group (p > 0.01). Anxiety score decreased 13.7% in the intervention group versus 2.8% in the control group (p < 0.01), and self-esteem score increased 2.3% in the intervention group and decreased 0.1% in the control group after the end of the program (p < 0.0001). No significant change was observed in the depressive score. Student participation and compliance with the program was > 80%. To conclude, a school-based program to improve physical activity in adolescents of low socioeconomic status, obtained a high level of participation and achieved significant benefits in terms of physical fitness and mental health status.", "Burns are associated with longer hospital stay, permanent disfigurement and emotional stress disorders, and represent a health problem, especially among economically and socially deprived populations, such as the Bedouin population in Israel, hence the importance of intervention programmes. The objective of this research was to examine the extent to which the effect of a visual one-session burn prevention programme was determined by the type of medium used. We also examined the possibility that fear motivates action only when someone feels confident in his/her ability to control the threat. Data were based on the pre-/post-programme self-report questionnaires administered to a randomly selected three-group sample of 12- to 13-year-old Bedouin children (n=179). All three sessions were identical, but differed in the type of medium used: slides (S), video (V), or slides and video consecutively (S + V). We measured health beliefs (perceived threat, internal/external control, self-efficacy) and sense of coherence (SOC), both before and 2 months after completion of the intervention. We also measured post-programme fear reaction and the improvement in burn-related knowledge, understanding and safety behaviour as the outcome measure. No significant post-programme differences between intervention groups were found, either in terms of outcome measure or in terms of health beliefs and SOC. However, within- person analysis indicated that the S group participants had the highest level of post-exposure fear and a decrease in luck control over injuries. The S + V group demonstrated the lowest within change. The hierarchical regression analysis revealed that self-efficacy, fear, higher socio-economic status and female gender predicted improvement. As hypothesized, the interaction between fear and self-efficacy added significantly to prediction. It seems that health beliefs and demographic characteristics were more powerful in predicting the effect of the intervention than the choice of medium per se. A multifaceted approach and more comprehensive interventions are needed in order to promote health among disadvantaged populations.", "Exercise rehabilitation is recommended increasingly for patients with chronic obstructive pulmonary disease (COPD). This study examined the effect of exercise and education on 79 older adults (M age = 66.6 +/- 6.5 years; 53% female) with COPD, randomly assigned to 10 weeks of (a) exercise, education, and stress management (EXESM; n = 29); (b) education and stress management (ESM; n = 25); or (c) waiting list (WL; n = 25). EXESM included 37 sessions of exercise, 16 educational lectures, and 10 weekly stress management classes. ESM included only the 16 lectures and 10 stress management classes. Before and after the intervention, assessments were conducted of physiological functioning (pulmonary function, exercise endurance), psychological well-being (depression, anxiety, quality of life), and cognitive functioning (attention, motor speed, mental efficiency, verbal processing). Repeated measures multivariate analysis of variance indicated that EXESM participants experienced changes not observed among ESM and WL participants, including improved endurance, reduced anxiety, and improved cognitive performance (verbal fluency).", "Self-directed and supervised exercise were compared with usual care in a clinical trial designed to evaluate the effect of structured exercise on physical functioning and other dimensions of health-related quality of life in women with stages I and II breast cancer.\n One hundred twenty-three women with stages I and II breast cancer completed baseline evaluations of generic and disease- and site-specific health-related quality of life, aerobic capacity, and body weight. Participants were randomly allocated to one of three intervention groups: usual care (control group), self-directed exercise, or supervised exercise. Quality of life, aerobic capacity, and body weight measures were repeated at 26 weeks. The primary outcome was the change in the Short Form-36 physical functioning scale between baseline and 26 weeks.\n Physical functioning in the control group decreased by 4.1 points, whereas it increased by 5.7 points and 2.2 points in the self-directed and supervised exercise groups, respectively (P =.04). Post hoc analysis showed a moderately large (and clinically important) difference between the self-directed and control groups (9.8 points; P =.01) and a more modest difference between the supervised and control groups (6.3 points; P =.09). No significant differences between groups were observed for changes in quality of life scores. In a secondary analysis of participants stratified by type of adjuvant therapy, supervised exercise improved aerobic capacity (+3.5 mL/kg/min; P =.01) and reduced body weight (-4.8 kg; P <.05) compared with usual care only in participants not receiving chemotherapy.\n Physical exercise can blunt some of the negative side effects of breast cancer treatment, including reduced physical functioning. Self-directed exercise is an effective way to improve physical functioning compared with usual care. In participants not receiving chemotherapy, supervised exercise may increase aerobic capacity and reduce body weight compared with usual care." ]	Lay-led self-management education programmes may lead to small, short-term improvements in participants' self-efficacy, self-rated health, cognitive symptom management, and frequency of aerobic exercise. There is currently no evidence to suggest that such programmes improve psychological health, symptoms or health-related quality of life, or that they significantly alter healthcare use. Future research on such interventions should explore longer term outcomes, their effect on clinical measures of disease and their potential role in children and adolescents.
CD006135	[ "15727582", "17208601", "11069570", "11297958", "11799376", "12548058", "12589361", "1536784", "16839405", "16512804" ]	[ "Probiotics in the treatment of atopic eczema/dermatitis syndrome in infants: a double-blind placebo-controlled trial.", "Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: a randomized, double-blind, placebo-controlled trial.", "Probiotics in the management of atopic eczema.", "Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial.", "Probiotics during pregnancy and breast-feeding might confer immunomodulatory protection against atopic disease in the infant.", "Probiotic bacteria in the management of atopic disease: underscoring the importance of viability.", "Effect of probiotic Lactobacillus strains in children with atopic dermatitis.", "A controlled trial of traditional Chinese medicinal plants in widespread non-exudative atopic eczema.", "No effects of probiotics on atopic dermatitis in infancy: a randomized placebo-controlled trial.", "Prebiotics and synbiotics: two promising approaches for the treatment of atopic dermatitis in children above 2 years." ]	[ "Probiotic bacteria are suggested to reduce symptoms of the atopic eczema/dermatitis syndrome (AEDS) in food-allergic infants. We aimed to investigate whether probiotic bacteria have any beneficial effect on AEDS.\n Follow-up of severity of AEDS by the Severity Scoring of Atopic Dermatitis (SCORAD) index in 230 infants with suspected cow's milk allergy (CMA) receiving, in a randomized double-blinded manner, concomitant with elimination diet and skin treatment, Lactobacillus GG (LGG), a mixture of four probiotic strains, or placebo for 4 weeks. Four weeks after the treatment, CMA was diagnosed with a double-blind placebo-controlled (DBPC) milk challenge in 120 infants.\n In the whole group, mean SCORAD (at baseline 32.5) decreased by 65%, but with no differences between treatment groups immediately or 4 weeks after the treatment. No treatment differences were observed in infants with CMA either. In IgE-sensitized infants, however, the LGG group showed a greater reduction in SCORAD than did the placebo group, -26.1 vs-19.8 (P=0.036), from baseline to 4 weeks after the treatment. Exclusion of infants who had received antibiotics during the study reinforced the findings in the IgE-sensitized subgroup.\n Treatment with LGG may alleviate AEDS symptoms in IgE-sensitized infants but not in non-IgE-sensitized infants.", "The increase in allergic diseases is attributed to a relative lack of microbial stimulation of the infantile gut immune system. Probiotics, live health-promoting microbes, might offer such stimulation.\n We studied the effect of a mixture of 4 probiotic bacterial strains along with prebiotic galacto-oligosaccharides in preventing allergic diseases.\n We randomized 1223 pregnant women carrying high-risk children to use a probiotic preparation or a placebo for 2 to 4 weeks before delivery. Their infants received the same probiotics plus galacto-oligosaccharides (n = 461) or a placebo (n = 464) for 6 months. At 2 years, we evaluated the cumulative incidence of allergic diseases (food allergy, eczema, asthma, and allergic rhinitis) and IgE sensitization (positive skin prick test response or serum antigen-specific IgE level >0.7 kU/L). Fecal bacteria were analyzed during treatment and at age 2 years.\n Probiotic treatment compared with placebo showed no effect on the cumulative incidence of allergic diseases but tended to reduce IgE-associated (atopic) diseases (odds ratio [OR], 0.71; 95% CI, 0.50-1.00; P = .052). Probiotic treatment reduced eczema (OR, 0.74; 95% CI, 0.55-0.98; P = .035) and atopic eczema (OR, 0.66; 95% CI, 0.46-0.95; P = .025). Lactobacilli and bifidobacteria more frequently (P < .001) colonized the guts of supplemented infants.\n Probiotic treatment showed no effect on the incidence of all allergic diseases by age 2 years but significantly prevented eczema and especially atopic eczema. The results suggest an inverse association between atopic diseases and colonization of the gut by probiotics.\n The prevention of atopic eczema in high-risk infants is possible by modulating the infant's gut microbiota with probiotics and prebiotics.", "Over the last two decades the incidence of allergic diseases has increased in industrialized countries, and consequently new approaches have to be explored.\n The potential of probiotics to control allergic inflammation at an early age was assessed in a randomized double-blind placebo-controlled study.\n A total of 27 infants, mean age 4.6 months, who manifested atopic eczema during exclusive breast-feeding and who have had no exposure to any infant or substitute formula were weaned to probiotic-supplemented, Bifidobacterium lactis Bb-12 or Lactobacillus strain GG (ATCC 53103), extensively hydrolysed whey formulas or to the same formula without probiotics. The extent and severity of atopic eczema, the growth and nutrition of infants, and concentrations of circulating cytokines/chemokines and soluble cell surface adhesion molecules in serum and methyl-histamine and eosinophilic protein X in urine were determined.\n The SCORAD score reflecting the extent and severity of atopic eczema was 16 (7-25) during breast-feeding, median (interquartile range). After 2 months, a significant improvement in skin condition occurred in patients given probiotic-supplemented formulas, as compared to the unsupplemented group; chi(2) = 12.27, P = 0.002. SCORAD decreased in the Bifidobacterium lactis Bb-12 group to 0 (0-3.8), and in the Lactobacillus GG group to 1 (0.1-8.7), vs unsupplemented 13.4 (4.5-18.2), median (interquartile range), in parallel with a reduction in the concentration of soluble CD4 in serum and eosinophilic protein X in urine.\n The results provide the first clinical demonstration of specific probiotic strains modifying the changes related to allergic inflammation. The data further indicate that probiotics may counteract inflammatory responses beyond the intestinal milieu. The combined effects of these probiotic strains will guide infants through the weaning period, when sensitization to newly encountered antigens is initiated. The probiotic approach may thus offer a new direction in the search for future foods for allergy treatment and prevention strategies.", "Reversal of the progressive increase in frequency of atopic disease would be an important breakthrough for health care and wellbeing in western societies. In the hygiene hypothesis this increase is attributed to reduced microbial exposure in early life. Probiotics are cultures of potentially beneficial bacteria of the healthy gut microflora. We assessed the effect on atopic disease of Lactobacillus GG (which is safe at an early age and effective in treatment of allergic inflammation and food allergy).\n In a double-blind, randomised placebo-controlled trial we gave Lactobacillus GG prenatally to mothers who had at least one first-degree relative (or partner) with atopic eczema, allergic rhinitis, or asthma, and postnatally for 6 months to their infants. Chronic recurring atopic eczema, which is the main sign of atopic disease in the first years of life, was the primary endpoint.\n Atopic eczema was diagnosed in 46 of 132 (35%) children aged 2 years. Asthma was diagnosed in six of these children and allergic rhinitis in one. The frequency of atopic eczema in the probiotic group was half that of the placebo group (15/64 [23%] vs 31/68 [46%]; relative risk 0.51 [95% CI 0.32-0.84]). The number needed to treat was 4.5 (95% CI 2.6-15.6).\n Lactobacillus GG was effective in prevention of early atopic disease in children at high risk. Thus, gut microflora might be a hitherto unexplored source of natural immunomodulators and probiotics, for prevention of atopic disease.", "The prevalence of atopic diseases is increasing throughout the Western world, and means of primary prevention are needed to reverse this trend. The role of breast-feeding, the best source of infant nutrition, in protection against atopic disease remains elusive. In this double-blinded, placebo-controlled study of 62 mother-infant pairs, it is shown that administering probiotics to the pregnant and lactating mother increased the immunoprotective potential of breast milk, as assessed by the amount of anti-inflammatory transforming growth factor beta2 (TGF-beta2) in the milk (2885 pg/mL [95% CI, 1624-4146] in mothers receiving probiotics vs 1340 pg/mL [95% CI, 978-1702] in mothers receiving placebo; P =.018). The risk of developing atopic eczema during the first 2 years of life in infants whose mothers received probiotics was significantly reduced in comparison with that in infants whose mothers received placebo (15% and 47%, respectively; relative risk, 0.32 [95% CI, 0.12-0.85]; P =.0098). Maternal atopy was a clear risk factor for atopic eczema in the infant. The infants most likely to benefit from maternal probiotic supplementation were those with an elevated cord blood IgE concentration. Administering probiotics during pregnancy and breast-feeding thus offers a safe and effective mode of promoting the immunoprotective potential of breast-feeding and provides protection against atopic eczema during the first 2 years of life.", "The aim of this study was to assess the efficacy of oral supplementation of viable and heat-inactivated probiotic bacteria in the management of atopic disease and to observe their effects on the composition of the gut microbiota.\n The study population included 35 infants with atopic eczema and allergy to cow's milk. At a mean age of 5.5 months, they were assigned in a randomized double-blind manner to receive either extensively hydrolyzed whey formula (placebo group) or the same formula supplemented with viable (viable LGG group) or heat-inactivated Lactobacillus GG (heat-inactivated LGG group), respectively. The changes in symptoms were assessed by the SCORAD method and the presence of some predominant bacterial genera in the feces detected with 16S rRNA-specific probes.\n The treatment with heat-inactivated LGG was associated with adverse gastrointestinal symptoms and diarrhea. Consequently, the recruitment of patients was stopped after the pilot phase. Within the study population, atopic eczema and subjective symptoms were significantly alleviated in all the groups; the SCORAD scores (interquartile range) decreased from 13 (range, 4-29) to 8 (range, 0-29) units in the placebo group, from 19 (range, 4-47) to 5 (range, 0-18) units in the viable LGG group, and from 15 (range, 0-29) to 7 (range, 0-26) units in the heat-inactivated LGG group. The decrease in the SCORAD scores within the viable LGG group tended to be greater than within the placebo group. The treatments did not appear to affect the bacterial numbers within the genera enumerated.\n Supplementation of infant formulas with viable but not heat-inactivated LGG is a potential approach for the management of atopic eczema and cow's milk allergy.", "Recent studies suggest that oral bacteriotherapy with probiotics might be useful in the management of atopic dermatitis (AD).\n The purpose of this investigation was to evaluate the clinical and anti-inflammatory effect of probiotic supplementation in children with AD.\n In a double-blind, placebo-controlled, crossover study, 2 probiotic Lactobacillus strains (lyophilized Lactobacillus rhamnosus 19070-2 and Lactobacillus reuteri DSM 122460) were given in combination for 6 weeks to 1- to 13-year-old children with AD. The patients' evaluations were registered after each intervention (ie, better, unchanged, or worse). The clinical severity of the eczema was evaluated by using the scoring atopic dermatitis (SCORAD) score. As inflammatory markers, eosinophil cationic protein in serum and cytokine production by PBMCs were measured.\n After active treatment, 56% of the patients experienced improvement of the eczema, whereas only 15% believed their symptoms had improved after placebo (P =.001). The total SCORAD index, however, did not change significantly. The extent of the eczema decreased during active treatment from a mean of 18.2% to 13.7% (P =.02). The treatment response was more pronounced in allergic patients (at least one positive skin prick test response and elevated IgE levels), and in this group the SCORAD score decreased (P =.02 compared with nonallergic patients). During active treatment, serum eosinophil cationic protein levels decreased (P =.03). No significant changes in the production of the cytokines IL-2, IL-4, IL-10, or IFN-gamma were found.\n A combination of L rhamnosus 19070-2 and L reuteri DSM 122460 was beneficial in the management of AD. The effect was more pronounced in patients with a positive skin prick test response and increased IgE levels.", "Severe and widespread atopic eczema often fails to respond adequately to currently available therapies. Following the observation of substantial benefit in patients receiving oral treatment with daily decoctions of traditional Chinese medicinal plants, we undertook a placebo-controlled double-blind trial of a specific prescription formulated for widespread non-exudative atopic eczema. Forty-seven children were given active treatment and placebo in random order, each for 8 weeks, with an intervening 4-week wash-out period. Thirty-seven children tolerated the treatment and completed the study. Response to active treatment was superior to response to placebo, and was clinically valuable. There was no evidence of haematological, renal or hepatic toxicity. These findings anticipate a wider therapeutic potential for traditional Chinese medicinal plants in this disease, and other skin diseases.", "Studies have been performed suggesting that administration of probiotics may have therapeutic and/or preventive benefits in the development of sensitization and atopic disease, particularly in infants with atopic dermatitis (AD).\n The purpose of this study was to evaluate the clinical and immunological effects of supplementation of a hydrolysed formula with two probiotic strains of bacteria on symptoms of AD in infancy.\n We conducted a randomized, double-blind, placebo-controlled study. After 4-6 weeks of baseline and double-blind, placebo-controlled challenges for diagnosis of cow's milk allergy (CMA), infants less than 5 months old with AD received a hydrolysed whey-based formula as placebo (n = 17), or supplemented with either Lactobacillus rhamnosus (n = 17) or Lactobacillus GG (n = 16) for 3 months. Before, during and after intervention, the clinical severity of AD was evaluated using SCORing index Atopic Dermatitis (SCORAD). Allergic sensitization was evaluated by measurement of total IgE and a panel of food-specific IgEs as well as skin prick testing for cow's milk. Inflammatory parameters were blood eosinophils, eosinophil protein X in urine, fecal alpha-1-antitrypsin and production of IL-4, IL-5 and IFN-gamma by peripheral blood mononuclear cells after polyclonal stimulation.\n No statistically significant effects of probiotic supplementation on SCORAD, sensitization, inflammatory parameters or cytokine production between groups were found. Only four infants were diagnosed with CMA.\n We found no clinical or immunological effect of the probiotic bacteria used in infants with AD. Our results indicate that oral supplementation with these probiotic bacterial strains will not have a significant impact on the symptoms of infantile AD.", "Appropriate use of prebiotics and optimal combinations of probiotics and prebiotics (synbiotics) could allow significantly better results to be obtained in the treatment of atopic dermatitis (AD).\n To evaluate the efficiency of synbiotics when compared with prebiotics alone (control group) in the treatment of moderate and severe AD in children aged 2 years and over.\n Double-blind prospective randomized study performed on children aged at least 2 years presenting AD with a minimum SCORing Atopic Dermatitis (SCORAD) score of 15. A dose of 1.2 x 10(9) colony-forming units Lactobacillus rhamnosus Lcr35 plus prebiotic preparation or an identically appearing prebiotic preparation alone was given three times a day for 3 months. Patients' diet and usual treatment for AD remained unchanged during the study period. Efficiency was evaluated using the SCORAD score. Use of topical drugs was noted.\n A total of 48 patients were originally enrolled; nine did not complete the study. In synbiotic group, the mean values of the total SCORAD score was 39.1 before treatment vs 20.7 after 3 months of treatment (P < 0.0001). In the prebiotic group, the mean of the total SCORAD score was 39.3 before the treatment vs 24.0 after 3 months (P < 0.0001). After 3 months of treatment, no statistical differences between the two treatment groups with regard to the total SCORAD score were noted (P = 0.535). Neither were there any statistical differences in the total use of ointment between patients receiving prebiotics or synbiotics (P = 0.966) over the study period. Tolerance was excellent in both groups.\n Both synbiotics and prebiotics used alone seem able to significantly improve the manifestations of AD in children aged 2 years and over." ]	The evidence suggests that probiotics are not an effective treatment for eczema, and probiotic treatment carries a small risk of adverse events.
CD006886	[ "18855829", "17074945", "15991780", "12709522", "17995993", "10615236", "2485283", "17034446", "19392908", "19524389", "16185216", "19087949", "9842079", "16436397" ]	[ "Extended cognitive behavior therapy for cigarette smoking cessation.", "A randomized controlled trial of a smoking cessation intervention among people with a psychotic disorder.", "A randomised controlled trial to evaluate the efficacy of a nurse-provided intervention for hospitalised smokers.", "One year effectiveness of an individualised smoking cessation intervention at the workplace: a randomised controlled trial.", "Proactive interventions for smoking cessation in general medical practice: a quasi-randomized controlled trial to examine the efficacy of computer-tailored letters and physician-delivered brief advice.", "Maintaining abstinence from cigarette smoking: effectiveness of group counselling and factors predicting outcome.", "Relapse prevention versus broad spectrum treatment for smoking cessation: a comparison of efficacy.", "A randomized controlled trial to assess the effects of reimbursing the costs of smoking cessation therapy on sustained abstinence.", "Extended treatment of older cigarette smokers.", "Impact of a brief motivational smoking cessation intervention the Get PHIT randomized controlled trial.", "A randomized trial assessing the Five-Day Plan for smoking cessation.", "A digital smoking cessation program delivered through internet and cell phone without nicotine replacement (happy ending): randomized controlled trial.", "[Clinical trial of 2 tobacco use cessation interventions in primary care].", "A randomised control study of a fully automated internet based smoking cessation programme." ]	[ "PRIMARY AIM: Examine the effectiveness of extended cognitive behavior therapy (CBT) in promoting longer-term smoking abstinence.\n Open-label treatment phase followed by extended treatment phase. Randomization conducted prior to entry into open-label treatment phase; analysis based on intention-to-treat to avoid threat of selection bias.\n Community smoking cessation clinic.\n A total of 304 adult smokers (> or = 18 years of age; > or = 10 cigarettes/day).\n Open-label (8 weeks): all participants received bupropion SR, nicotine patch, CBT. Extended treatment (12 weeks): participants received either CBT + voicemail monitoring and telephone counseling or telephone-based general support.\n Seven-day point prevalence abstinence, expired-air carbon monoxide.\n At week 20 follow-up, CBT produced a higher 7-day point prevalence abstinence rate: 45% versus 29%, P = 0.006; at 52 weeks the difference in abstinence rates (31% versus 27%) was not significant. History of depression was a moderator of treatment. Those with a positive history had a better treatment response at 20 weeks when assigned to the less intensive telephone support therapy (P < 0.05).\n The superiority of CBT to 20 weeks suggests that continued emphasis on the development of cognitive and behavioral strategies for maintaining non-smoking during an extended treatment phase may help smokers to maintain abstinence in the longer term. At present, the minimum duration of therapy is unknown.", "Despite extremely high rates of smoking among individuals with psychotic disorders and the associated financial and health costs, few studies have investigated the efficacy of smoking cessation interventions among this group. The purpose of this study was to compare an integrated psychological and nicotine replacement therapy intervention for people with a psychotic disorder with routine care alone.\n The authors recruited 298 regular smokers with a psychotic disorder residing in the community and randomly assigned them to a routine care comparison condition (N=151) or an eight-session, individually administered smoking cessation intervention (N=147), which consisted of nicotine replacement therapy, motivational interviewing, and cognitive behavior therapy. Outcome variables included continuous and point-prevalence abstinence rates, smoking reduction status, and changes in symptoms and functioning.\n While there were no overall differences between the treatment group and comparison group in abstinence rates, a significantly higher proportion of smokers who completed all treatment sessions stopped smoking at each of the follow-up occasions (point-prevalence rates: 3 months, 30.0% versus 6.0%; 6 months, 18.6% versus 4.0%; and 12 months, 18.6% versus 6.6%). Smokers who completed all treatment sessions were also more likely to have achieved continuous abstinence at 3 months (21.4% versus 4.0%). There was a strong dose-response relationship between treatment session attendance and smoking reduction status, with one-half of those who completed the intervention program achieving a 50% or greater reduction in daily cigarette consumption across the follow-ups, relative to less than one-fifth of the comparison subjects. There was no evidence of any associated deterioration in symptoms or functioning.\n These findings demonstrate the utility of a nicotine replacement therapy plus motivational interviewing/cognitive behavior therapy smoking cessation intervention among individuals with a psychotic disorder. Further development of more efficacious interventions is required for those who do not respond to existing interventions.", "Does the provision of a nurse-based intervention lead to smoking cessation in hospital patients?\n At tertiary teaching hospital in Newcastle, Australia, 4,779 eligible (aged 18-80, admitted for at least 24 hours, and able to provide informed consent) and consenting (73.4%) in-patients were recruited into a larger cross-sectional survey. 1,422 (29.7%) smokers (in the last 12 months) were randomly assigned to control (n = 711) or intervention group (n = 711). The brief nurse-delivered intervention incorporated: tailored information, assessment of withdrawal, offer of nicotine replacement therapy, booklets, and a discharge letter. Self-reported cessation at 12 months was validated with CO and salivary cotinine.\n There were no significant differences between groups in self-reported abstinence at three or 12 months post intervention, based on an intention to treat analysis. At three months, self-reported abstinence was 27.3% (I) and 27.5% (C); at 12 months was 18.5% (I) and 20.6% (C). There were no differences in validation of self-report between intervention and control groups at 12 months.\n This brief nurse-provided in-patient intervention did not significantly increase the smoking cessation rates compared with the control group at either three or 12-month follow-up.\n A systematic total quality improvement model of accountable outcome-focused treatment, incorporating assertive physician-led pharmacotherapy, routine assessment and recording of nicotine dependence (ICD 10 coding), in- and outpatient services and engagement from multidisciplinary teams of health professionals may be required to improve treatment modalities for this chronic addictive disorder.", "To assess the effectiveness of a smoking cessation intervention at the workplace. The intervention was adapted to smokers' tobacco dependence, and included minimal structured counselling at the first visit (5-8 minutes), nicotine patches for three months, and three sessions of counselling for reinforcement of abstinence (2-3 minutes) over a three month period.\n Open randomised trial with two groups: the intervention group, and the control group which was subjected to standard clinical practice, consisting of short (30 seconds to one minute) sporadic sessions of unstructured medical antismoking advice. The trial was carried out among 217 smokers of both sexes, aged 20-63 years, motivated to quit smoking and without contraindications for nicotine patches, who were employees at a public transport company and at two worksites of an electric company. The main outcome measure was self reported tobacco abstinence confirmed by carbon monoxide in expired air </=10 ppm. Analysis was performed according to intention-to-treat.\n The rate of continuous abstinence at 12 months was 20.2% for the intervention versus 8.7% for the control group (OR: 2.58; 95% CI: 1.13 to 5.90; p = 0.025). In subgroup analyses, effectiveness of the intervention did not vary substantially with age, tobacco dependence, number of cigarettes smoked per day, number of years of tobacco consumption, degree of desire to quit smoking, time spent with smokers, subjective health, and presence of tobacco related symptoms. Weight gain at 12 months was similar for both groups (1.69 kg in the intervention v 2.01 kg in the control group; p = 0.21).\n A simple and easily generalisable intervention at the workplace is effective to achieve long term smoking cessation. In a setting similar to ours, nine subjects would have to be treated for three months for one to achieve continuous abstinence for 12 months.", "To test the efficacy of (i) computer-generated tailored letters and (ii) practitioner-delivered brief advice for smoking cessation against an assessment-only condition; and to compare both interventions directly.\n Quasi-randomized controlled trial.\n A total of 34 randomly selected general practices from a German region (participation rate 87%).\n A total of 1499 consecutive patients aged 18-70 years with daily cigarette smoking (participation rate 80%).\n The tailored letters intervention group received up to three individualized personal letters. Brief advice was delivered during routine consultation by the practitioner after an onsite training session. Both interventions were based on the Transtheoretical Model of behaviour change.\n Self-reported point prevalence and prolonged abstinence at 6-, 12-, 18- and 24-month follow-ups.\n Among participants completing the last follow-up, 6-month prolonged abstinence was 18.3% in the tailored letters intervention group, 14.8% in the brief advice intervention group and 10.5% in the assessment-only control group. Assuming those lost to follow-up to be smokers, the rates were 10.2%, 9.7% and 6.7%, respectively. Analyses including all follow-ups confirmed statistically significant effects of both interventions compared to assessment only. Using complete case analysis, the tailored letters intervention was significantly more effective than brief advice for 24-hour [odds ratio (OR) = 1.4; P = 0.047] but not for 7-day point prevalence abstinence (OR = 1.4; P = 0.068) for prolonged abstinence, or for alternative assumptions about participants lost to follow-up.\n The study demonstrated long-term efficacy of low-cost interventions for smoking cessation in general practice. The interventions are suitable to reach entire populations of general practices and smoking patients. Computer-generated letters are a promising option to overcome barriers to provide smoking cessation counselling routinely.", "The aim of the study was to assess the effectiveness of worksite group counselling interventions designed to prevent smoking relapse after abstinence has been achieved following 3 months therapy using group support and/or transdermal nicotine replacement therapy. After 3 months, abstinent subjects were randomly allocated either to a counselling group led by professional psychologists (PG), to a counselling group led by former smokers (SG) or to no intervention group (NG). The 3 and 12 months abstinence were defined, respectively, as a sustained smoking cessation during the last month, and the last 9 months. Complete abstinence was confirmed by expired carbon monoxide and by urine cotinine concentrations. The abstinence rate at 3 months was 35.1%. After 12 months abstinence rates were not statistically different in the PG, the SG and the NG (respectively 57.8, 53.4 and 49.6% of those randomised). In multivariate analyzes, baseline variables associated with 12 months abstinence were non-smoking family, gender (male), lower daily intake of nicotine and better psychological adjustment. Mean weight gain at 3 months in abstinent versus relapsed subjects, was respectively, 4.1 and 2.4 kg. Baseline variables associated with weight gain at 3 months were higher Fagerström score, gender (male) and professional status (blue collar worker). Group support after abstinence has been achieved did not significantly improve the abstinence. This study shows the difficulty of preventing smoking relapse with monthly group counselling. The results indicate the need to investigate further specific programmes focusing on factors such as gender, family, nicotine dependence, psychological and weight concerns/issues which may precipitate relapse.", "The efficacy of a smoking cessation relapse prevention (RP) program, emphasizing cognitive-behavioral coping skills, was compared to that of a broad spectrum (BS) program, which emphasized behavioral skills. It was hypothesized that the RP program would be more effective in producing long-term abstinence, compared to the BS package. Abstinence rates validated by saliva thiocyanate and carbon monoxide, as well as self-report of smoking reduction, were measured at posttreatment, 3 and 6 months. No differences in posttreatment quit rates were found between the two groups, although both programs produced significantly higher quit rates than the wait-list control group. Contrary to prediction, the BS group produced marginally significantly greater abstinence at 3 months. No differences in abstinence were found at 6 months. Reduction in cigarette consumption was marginally significantly greater for the BS group at 3 and 6 months. Various mediators of treatment outcome were not found to influence success in quitting. There was a significant weight gain in those who quit.", "We studied whether reimbursement for smoking cessation treatment (SCT) can increase prolonged abstinence from smoking up to 2 years. SETTING, PARTICIPANTS AND DESIGN: From the general population, we recruited smokers and assigned them randomly to a control group (n = 634) or an intervention group (n = 632). For 6 months, participants in the intervention group could apply for reimbursement and received information regarding the reimbursed SCT. Participants in the control group received no reimbursement or information.\n In this follow-up study, prolonged abstinence from smoking was defined as reported being abstinent from at least 7 days before the end of reimbursement until the follow-up assessment 6 months or 2 years later.\n At 6 months after the end of reimbursement, 18 participants in the control group (2.8%) and 35 participants (5.5%) in the intervention group reported sustained abstinence for at least 6 months [odds ratio (OR) = 2.0, 95% confidence interval (CI) 1.1-3.6]. Two years after the reimbursement period, 10 participants in the control group (1.6%) and 27 participants in the intervention group (4.3%) still reported sustained abstinence (OR = 4.1, 95% CI 1.7-10.2). The overall effectiveness of SCT increased with reimbursement and was 22% in the intervention group and 8% in the control group after 2 years.\n Reimbursement may be an effective strategy to increase the prolonged abstinence rate even after 2 years.", "Tobacco dependence treatments achieve abstinence rates of 25-30% at 1 year. Low rates may reflect failure to conceptualize tobacco dependence as a chronic disorder. The aims of the present study were to determine the efficacy of extended cognitive behavioral and pharmacological interventions in smokers > or = 50 years of age, and to determine if gender differences in efficacy existed.\n Open randomized clinical trial.\n A free-standing, smoking treatment research clinic.\n A total of 402 smokers of > or = 10 cigarettes per day, all 50 years of age or older.\n Participants completed a 12-week treatment that included group counseling, nicotine replacement therapy (NRT) and bupropion. Participants, independent of smoking status, were then assigned randomly to follow-up conditions: (i) standard treatment (ST; no further treatment); (ii) extended NRT (E-NRT; 40 weeks of nicotine gum availability); (iii) extended cognitive behavioral therapy (E-CBT; 11 cognitive behavioral sessions over a 40-week period); or (iv) E-CBT plus E-NRT (E-combined; 11 cognitive behavioral sessions plus 40 weeks nicotine gum availability).\n Primary outcome variable was 7-day point prevalence cigarette abstinence verified biochemically at weeks 24, 52, 64 and 104.\n The most clinically important findings were significant main effects for treatment condition, time and the treatment x time interaction. The E-CBT condition produced high cigarette abstinence rates that were maintained throughout the 2-year study period [(week 24 (58%), 52 (55%), 64 (55%) and 104 (55%)], and was significantly more effective than E-NRT and ST across that period. No other treatment condition was significantly different to ST. No effects for gender were found.\n Extended cognitive behavioral treatments can produce high and stable cigarette abstinence rates for both men and women. NRT does not add to the efficacy of extended CBT, and may hamper its efficacy. Research is needed to determine if these results can be replicated in a sample with a greater range of ages, and improved upon with the addition of medications other than NRT.", "Few studies have rigorously evaluated whether providing biologically based health-risk feedback is more effective than standard interventions in increasing smokers' motivation to quit and their long-term abstinence.\n An RCT was conducted from 2005 to 2008. Data were analyzed in 2008.\n Smokers (N=536) were recruited from the community, regardless of their interest in quitting smoking.\n Smokers either received brief ( approximately 20 minutes), personally tailored counseling sessions based on their lung functioning, carbon monoxide (CO) exposure, and smoking-related health conditions, or they received generic smoking-risk information and personalized counseling about their diet, BMI, and physical activity. All were advised to quit smoking and were offered access to a free phone-counseling program.\n Treatment utilization and abstinence at 6 and 12 months post-intervention.\n Participants who received the experimental treatment demonstrated no greater motivation to quit, use of treatment services, or abstinence compared to controls at either follow-up assessment. In fact, controls reported greater motivation to quit at 12 months (M 3.42 vs 3.20, p=0.03), greater use of pharmacotherapy at 6 months (37.8% vs 28.0%, p=0.02), and greater 30-day point prevalent abstinence at 6 months, after controlling for relevant covariates (10.8% vs 6.4%, adjusted p=0.04).\n The present study found no support for adding a personalized health-risk assessment emphasizing lung health and CO exposure to generic cessation advice and counseling for community-based smokers not otherwise seeking treatment.\n NCT00169260.", "To evaluate the effectiveness of the Five-Day Plan (FDP) in helping smokers to stop smoking.\n Randomized controlled trial comparing intervention and control groups. The primary outcome measure was 12 months continuous abstinence verified by expired air carbon monoxide concentration. Secondary outcome measures were self-reported abstinence at end of treatment, at 3 and 6 months.\n Six towns in France.\n 228 smokers, recruited by newspaper and radio advertisement, aged 18 years or over and willing to make an attempt to quit smoking.\n The Intervention group (119 participants) received the FDP, which is a behavioural group-based treatment programme that has been in operation in France since 1965. It involves five consecutive evening behavioural therapy sessions. The Control group (109 participants) received a single session discussing the health effects of smoking.\n In the Intervention group, 67 participants (56%) quit smoking at the end of the FDP. After three months this number had been reduced to 30 (25%) and to 19 (16%) by the end of one year. In the Control group these numbers were 14 (13%) and 12 (11%), respectively, after three and 12 months. When considering the rate of cessation without lapse after one year a significant difference was observed with a 13% rate in the Intervention group and 3% in the Control group (P = 0.004).\n The FDP may be considered as an aid for smokers who want to quit.", "Happy Ending (HE) is an intense 1-year smoking cessation program delivered via the Internet and cell phone. HE consists of more than 400 contacts by email, Web pages, interactive voice response, and short message service technology. HE includes a craving helpline and a relapse prevention system, providing just-in-time therapy. All the components of the program are fully automated.\n The objectives were to describe the rationale for the design of HE, to assess the 12-month efficacy of HE in a sample of smokers willing to attempt to quit without the use of nicotine replacement therapy, and to explore the potential effect of HE on coping planning and self-efficacy (prior to quitting) and whether coping planning and self-efficacy mediate treatment effect.\n A two-arm randomized controlled trial was used. Subjects were recruited via Internet advertisements and randomly assigned to condition. Inclusion criteria were willingness to quit on a prescribed day without using nicotine replacement and being aged 18 years or older. The intervention group received HE, and the control group received a 44-page self-help booklet. Abstinence was defined as \"not even a puff of smoke, for the last seven days\" and was assessed by means of Internet surveys or telephone interviews 1, 3, 6, and 12 months postcessation. The main outcome was repeated point abstinence (ie, abstinence at all four time points). Coping planning and self-efficacy were measured at baseline and at the end of the preparation phase (ie, after 2 weeks of treatment, but prior to cessation day).\n A total of 290 participants received either the HE intervention (n=144) or the control booklet (n=146). Using intent-to-treat analysis, participants in the intervention group reported clinically and statistically significantly higher repeated point abstinence rates than control participants (20% versus 7%, odds ratio [OR] = 3.43, 95% CI = 1.60-7.34, P = .002). Although no differences were observed at baseline, by the end of the preparation phase, significantly higher levels of coping planning (t(261) = 3.07, P = .002) and precessation self-efficacy (t(261) = 2.63, P = .01) were observed in the intervention group compared with the control group. However, neither coping planning nor self-efficacy mediated long-term treatment effect. For point abstinence 1 month after quitting, however, coping planning and self-efficacy showed a partial mediation of the treatment effect.\n This 12-month trial documents a long-term treatment effect of a fully automated smoking cessation intervention without the use of nicotine replacement therapy. The study adds to the promise of using digital media in supporting behavior change.", "To study the efficacy of two types of intervention to stop tobacco dependency.\n Randomised clinical trial.\n Primary care centre.\n Smokers recruited from among the health centre users through the preventive activities and health promotion programme.\n Independent variable: type of intervention. General variables: age, sex, marital status, educational level, work situation, cohabitation with children, smokers at home, number of years smoking, type of tobacco. There were two types of intervention: a) Minimal Intervention (MI). b) Advanced Intervention (AI). 54 patients were included, with 6 losses. 21 were assigned at random to the MI group and 27 to the AI group. Progress was measured at 15 days, 1 month, 3 months, 6 months and a year.\n In the MI, 23.8% were abstinent at 15 days; the same percentage at one month and 3 months; 19% at 6 months; and 14.3% remained abstinent after a year. In the AI, 51.9% were abstinent at 15 days; 48.1% at both one and 3 months; 25.9% at 6 months; and 22.2% were still not smoking after a year. No significant differences between the two interventions were found in any of the observations.\n These data do not show that one intervention is better than the other. With the passage of time the effect of the intervention decreased in both groups.", "The objective of this project was to test the short term (90 days) efficacy of an automated behavioural intervention for smoking cessation, the \"1-2-3 Smokefree\" programme, delivered via an internet website.\n Randomised control trial. Subjects surveyed at baseline, immediately post-intervention, and 90 days later.\n The study and the intervention occurred entirely via the internet site. Subjects were recruited primarily via worksites, which referred potential subjects to the website.\n The 351 qualifying subjects were notified of the study via their worksite and required to have internet access. Additionally, subjects were required to be over 18 years of age, smoke cigarettes, and be interested in quitting smoking in the next 30 days. Eligible subjects were randomly assigned individually to treatment or control condition by computer algorithm.\n The intervention consisted of a video based internet site that presented current strategies for smoking cessation and motivational materials tailored to the user's race/ethnicity, sex, and age. Control subjects received nothing for 90 days and were then allowed access to the programme.\n The primary outcome measure was abstinence from smoking at 90 day follow up.\n At follow up, the cessation rate at 90 days was 24.1% (n = 21) for the treatment group and 8.2% (n = 9) for the control group (p = 0.002). Using an intent-to-treat model, 12.3% (n = 21) of the treatment group were abstinent, compared to 5.0% (n = 9) in the control group (p = 0.015).\n These evaluation results suggest that a smoking cessation programme, with at least short term efficacy, can be successfully delivered via the internet." ]	Psychosocial smoking cessation interventions are effective in promoting abstinence at 1 year, provided they are of sufficient duration. Further studies, with longer follow-up, should compare different psychosocial intervention strategies, or the addition of a psychosocial intervention strategy to pharmacological therapy (e.g. nicotine replacement therapy) compared with pharmacological treatment alone.
CD004407	[ "15195321", "2871241", "16865547", "9154545", "2068243", "15950329", "12415036", "8147091", "19952979", "15364187", "20222892", "19146903", "19720365", "1398956", "8242506", "17204517", "2807523", "14575762", "8228350", "7017582", "10775784", "15530676", "14551493", "15964483", "14615149", "18483372", "10930676", "16028125", "18845551", "18391753", "10569747", "16624457", "3020494", "20202055", "9359740", "15877763", "15526058", "22154769", "8394646", "10376617", "8501336", "7934537", "12744870", "9812477", "12443672", "9615498", "5302328", "16940831", "11747915", "2798746", "11144370", "11803071", "9323616", "7798683", "15723921", "2119897", "2087879", "11920300", "18827210", "9388905" ]	[ "Statistical analysis of MMR vaccine adverse events on aseptic meningitis using the case cross-over design.", "Frequency of true adverse reactions to measles-mumps-rubella vaccine. A double-blind placebo-controlled trial in twins.", "MMR-vaccine and regression in autism spectrum disorders: negative results presented from Japan.", "Risk of hospitalization because of aseptic meningitis after measles-mumps-rubella vaccination in one- to two-year-old children: an analysis of the Vaccine Safety Datalink (VSD) Project.", "A randomised single blind trial of a combined mumps measles rubella vaccine to evaluate serological response and reactions in the UK population.", "The effectiveness of the mumps component of the MMR vaccine: a case control study.", "Neurologic disorders after measles-mumps-rubella vaccination.", "Safety, immunogenicity and limited efficacy study of a recombinant Plasmodium falciparum circumsporozoite vaccine in Thai soldiers.", "Lack of association between measles-mumps-rubella vaccination and autism in children: a case-control study.", "MMR vaccination and pervasive developmental disorders: a case-control study.", "No demonstrable association between the Leningrad-Zagreb mumps vaccine strain and aseptic meningitis in a large clinical trial in Egypt.", "No evidence of an increase of bacterial and viral infections following Measles, Mumps and Rubella vaccine.", "Randomized, double-blind, placebo-controlled trial to evaluate the safety and immunogenicity of live oral cholera vaccine 638 in Cuban adults.", "Safety and immunogenicity in North Americans of a single dose of live oral cholera vaccine CVD 103-HgR: results of a randomized, placebo-controlled, double-blind crossover trial.", "Illness after measles-mumps-rubella vaccination.", "Risks of convulsion and aseptic meningitis following measles-mumps-rubella vaccination in the United Kingdom.", "Preliminary assessment of the safety and immunogenicity of live oral cholera vaccine strain CVD 103-HgR in healthy Thai adults.", "Non-clinical and phase I clinical trials of a Vero cell-derived inactivated Japanese encephalitis vaccine.", "Safety, immunogenicity, and transmissibility of single-dose live oral cholera vaccine strain CVD 103-HgR in 24- to 59-month-old Indonesian children.", "Clinical and serologic evaluation of measles, mumps, and rubella (HPV-77:DE-5 and RA 27/3) virus vaccines, singly and in combination.", "Safety and immunogenicity of a three-component blood-stage malaria vaccine in adults living in an endemic area of Papua New Guinea.", "Efficacy of postexposure immunization with live attenuated varicella vaccine in the household setting--a pilot study.", "Safety, immunogenicity and efficacy in healthy infants of G1 and G2 human reassortant rotavirus vaccine in a new stabilizer/buffer liquid formulation.", "Safety and immunogenicty of RTS,S/AS02A candidate malaria vaccine in Gambian children.", "Randomized, phase II dose-finding studies of a modified tick-borne encephalitis vaccine: evaluation of safety and immunogenicity.", "Pilot study of vaccination with recombinant CEA-MUC-1-TRICOM poxviral-based vaccines in patients with metastatic carcinoma.", "Safety and immunogenicity of adjuvanted and unadjuvanted subunit influenza vaccines administered intranasally to healthy adults.", "Randomized, controlled study of the safety and immunogenicity of Peru-15, a live attenuated oral vaccine candidate for cholera, in adult volunteers in Bangladesh.", "Measles-mumps-rubella vaccination and asthma-like disease in early childhood.", "A multipeptide vaccine is safe and elicits T-cell responses in participants with advanced stage ovarian cancer.", "Randomized, double-blind, placebo-controlled, multicentered trial of the efficacy of a single dose of live oral cholera vaccine CVD 103-HgR in preventing cholera following challenge with Vibrio cholerae O1 El tor inaba three months after vaccination.", "Safety and immunogenicity of the modified adult tick-borne encephalitis vaccine FSME-IMMUN: results of two large phase 3 clinical studies.", "Varicella vaccine studies in healthy children and adults.", "Intralesional immunotherapy of common warts: successful treatment with mumps, measles and rubella vaccine.", "Short-term safety of live attenuated Japanese encephalitis vaccine (SA14-14-2): results of a randomized trial with 26,239 subjects.", "No effect of MMR withdrawal on the incidence of autism: a total population study.", "A randomised, double-blind, controlled vaccine efficacy trial of DNA/MVA ME-TRAP against malaria infection in Gambian adults.", "Safety, tolerability, and immunogenicity after 1 and 2 doses of zoster vaccine in healthy adults ≥60 years of age.", "Simultaneous administration of a diphtheria and tetanus toxoids and acellular pertussis vaccine with measles-mumps-rubella and oral poliovirus vaccines.", "Autism and measles, mumps, and rubella vaccine: no epidemiological evidence for a causal association.", "Safety and immunogenicity of the oral, whole cell/recombinant B subunit cholera vaccine in North American volunteers.", "Randomised trial of efficacy of SPf66 vaccine against Plasmodium falciparum malaria in children in southern Tanzania.", "Safety and immunogenicity of an oral, inactivated enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine in Bangladeshi children 18-36 months of age.", "[Efficacy and side effects following immunization with Salmonella typhi Vi capsular polysaccharide vaccine].", "Calibrated serological techniques demonstrate significant different serum response rates to an oral killed cholera vaccine between Swedish and Nicaraguan children.", "A single dose of live oral cholera vaccine CVD 103-HgR is safe and immunogenic in HIV-infected and HIV-noninfected adults in Mali.", "Cholera vaccine field trials in east Pakistan. 1. Reaction and antigenicity studies.", "Encephalopathy after whole-cell pertussis or measles vaccination: lack of evidence for a causal association in a retrospective case-control study.", "Efficacy of RTS,S/AS02 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in The Gambia: a randomised trial.", "An evaluation of measles, mumps and rubella vaccine in a population of Yorkshire infants.", "Immunogenicity and safety of a new liquid hexavalent combined vaccine compared with separate administration of reference licensed vaccines in infants.", "Outbreak of aseptic meningitis and mumps after mass vaccination with MMR vaccine using the Leningrad-Zagreb mumps strain.", "Phase 1 trial of a candidate rotavirus vaccine (RV3) derived from a human neonate.", "Long-term efficacy of active postexposure immunization of infants for prevention of hepatitis B virus infection. United States-People's Republic of China Study Group on Hepatitis B.", "No evidence of an association between MMR vaccine and gait disturbance.", "[Vaccination against malaria: initial trial with an ant-sporozoite vaccine, (NANP)3-TT (RO 40-2361) in Africa (Bobo-Dioulasso, Burkina Faso)].", "Randomized double-blind placebo controlled trial to evaluate the safety and immunogenicity of the live oral cholera vaccine strain CVD 103-HgR in Swiss adults.", "A recombinant blood-stage malaria vaccine reduces Plasmodium falciparum density and exerts selective pressure on parasite populations in a phase 1-2b trial in Papua New Guinea.", "Effects of a reduced dose schedule and intramuscular administration of anthrax vaccine adsorbed on immunogenicity and safety at 7 months: a randomized trial.", "[Community trial for safety and immunogenicity of oral-administered lyophilized rBS-WC cholera vaccine]." ]	[ "Vaccination is quite effective in reducing the incidence of disease. However, it may cause some adverse events. For example, one of the adverse events of measles-mumps-rubella(MMR) vaccination is the occurrence of aseptic meningitis. Since the vaccination rate is usually quite high, it is not plausible to use popular study designs such as cohort or case-control studies. We considered a case cross-over design to investigate the association between MMR vaccination and aseptic meningitis in Korean children. We used the Cochran-Mantel-Haenszel(CMH) approach, and obtained a Mantel-Haenszel odds ratio estimator as a measure of association. However, the validity of case cross-over design or the CMH approach in vaccine adverse studies has not been fully investigated. In this paper, through Monte Carlo simulation studies, we show the appropriateness of the case cross-over design and the CMH approach. We also discuss alternative approaches such as Poisson regression using offset and a simple uniformity test. In conclusion, the case cross-over design seems useful to investigate the association between vaccination and occurrence of acute adverse events.\n Copyright 2004 John Wiley & Sons, Ltd.", "The vast majority of adverse reactions following immunisation of children with live measles-mumps-rubella (MMR) vaccine were shown in a double-blind, placebo-controlled, cross-over study in 581 twin pairs to be only temporally but not causally related to the vaccination. The true frequency of side-effects caused by MMR vaccine, estimated from the discordance rates of individual signs and symptoms between MMR vaccinees and their placebo-injected twins, was between 0.5 and 4.0%. Moreover, respiratory symptoms, nausea, and vomiting were observed more frequently in the placebo-injected group than in the MMR vaccinated group.", "It has been suggested that the measles, mumps, and rubella vaccine (MMR) is a cause of regressive autism. As MMR was used in Japan only between 1989 and 1993, this time period affords a natural experiment to examine this hypothesis. Data on 904 patients with autism spectrum disorders (ASD) were analyzed. During the period of MMR usage no significant difference was found in the incidence of regression between MMR-vaccinated children and non-vaccinated children. Among the proportion and incidence of regression across the three MMR-program-related periods (before, during and after MMR usage), no significant difference was found between those who had received MMR and those who had not. Moreover, the incidence of regression did not change significantly across the three periods.", "To assess the level of increased risk, if any, of hospitalizations for aseptic meningitis after Jeryl-Lynn mumps strain measles-mumps-rubella (MMR) vaccine in the Vaccine Safety Datalink population.\n A possible increased risk of aseptic meningitis 8 to 14 days after receipt of MMR was observed in a preliminary screening analysis of automated data from the Vaccine Safety Datalink (VSD) project Year 2 analysis. To further evaluate this association a retrospective 10-year matched case-control study was undertaken in the four health maintenance organizations (HMOs) in the VSD project. Cases ascertained from a broad scan of the automated data were validated against a standard case definition. Two controls matched on age, sex, HMO and HMO membership were assigned per case.\n The VSD project involves the cooperative collection of automated vaccination and medical outcome data from four large HMOs that currently have 500,000 children younger than 7 years of age under surveillance. Review of automated screening results from the first 2 years of data revealed a possible increased risk of aseptic meningitis 0 to 14 days after MMR with a relative risk of 3.61 (95% confidence interval, 1.0 to 13.1) although the total number of cases was small. Although the automated data had suggested a possible association of aseptic meningitis with MMR containing the Jeryl-Lynn strain of mumps, review of validated hospitalized cases during the observation period did not reveal evidence of an increased risk of aseptic meningitis after MMR containing the Jeryl-Lynn strain of mumps (odds ratio < 1.0 for all analyses).\n Although it is recognized that hospitalized cases represent a minority of the total cases of aseptic meningitis, it is reassuring that in this evaluation no increased risk of aseptic meningitis after MMR vaccine was found.", "Four hundred and twenty children were randomly assigned to receive either mumps measles rubella (MMR) vaccine (207) or measles vaccine (213) in a single blind study, to investigate the reactogenicity and serology of the MMR vaccine. There was no significant difference between the number of children developing symptoms after MMR vaccination to those developing symptoms after measles vaccination. Both vaccines are associated with a rash, temperature and restlessness five to thirteen days after vaccination. The serological response to measles vaccine was similar in both groups with 92-6% seroconverting with MMR, and 96-8% with measles. Seroconvertion against mumps and rubella with the MMR vaccine was 88% and 96% respectively. This study confirms the safety and efficacy of the MMR vaccine in a UK population.", "In 1998/1999, an outbreak of mumps occurred among children of a religious community in North East London. A case control study was conducted to assess the effectiveness of the mumps component of the MMR vaccine. One hundred and sixty-one cases of mumps were identified and 192 controls were selected. Fifty-one percent of cases and 77% of controls had a history at least one MMR vaccination. The observed effectiveness of any MMR vaccination adjusted for age, sex and general practice was 69% (95% CI: 41-84%). This is consistent with the results of other observational studies of mumps containing vaccines, but lower than the immunogenicity of mumps vaccines reported by clinical trials. This discrepancy is because observational studies tend to underestimate vaccine effectiveness, and because immunogenicity is not necessarily an accurate biological marker of vaccine effectiveness. Two doses of vaccine were more effective (88% (95% CI: 62-96%)) than a single dose (64% (95% CI: 40-78%)). The current two-dose vaccination programme remains the best method for controlling mumps infection in the community.", "The possibility of adverse neurologic events has fueled much concern about the safety of measles-mumps-rubella (MMR) vaccinations. The available evidence concerning several of the postulated complications is controversial. The aim of this study was to assess whether an association prevails between MMR vaccination and encephalitis, aseptic meningitis, and autism.\n A retrospective study based on linkage of individual MMR vaccination data with a hospital discharge register was conducted among 535 544 1- to 7-year-old children who were vaccinated between November 1982 and June 1986 in Finland. For encephalitis and aseptic meningitis, the numbers of events observed within a 3-month risk interval after vaccination were compared with the expected numbers estimated on the basis of occurrence of encephalitis and aseptic meningitis during the subsequent 3-month intervals. Changes in the overall number of hospitalizations for autism after vaccination throughout the study period were searched for. In addition, hospitalizations because of inflammatory bowel diseases were checked for the children with autism.\n Of the 535 544 children who were vaccinated, 199 were hospitalized for encephalitis, 161 for aseptic meningitis, and 352 for autistic disorders. In 9 children with encephalitis and 10 with meningitis, the disease developed within 3 months of vaccination, revealing no increased occurrence within this designated risk period. We detected no clustering of hospitalizations for autism after vaccination. None of the autistic children made hospital visits for inflammatory bowel diseases.\n We did not identify any association between MMR vaccination and encephalitis, aseptic meningitis, or autism.", "Thai soldiers were vaccinated with a recombinant protein derived from the central repeat region of the circumsporozoite (CS) protein of Plasmodium falciparum conjugated to Toxin A (detoxified) of Pseudomonas aeruginosa (R32Tox-A) to evaluate its safety, immunogenicity and efficacy. In a randomized, double-blind manner, 199 volunteers received either R32Tox-A or a control vaccine at 0, 8 and 16 weeks. Immunization was performed in a malaria non-transmission area, after completion of which volunteers were deployed to an endemic border area and monitored closely to allow early detection and treatment of infection. The vaccine was found to be safe and to elicit antibody responses in all vaccinees. Peak CS antibody (IgG) concentrations in malaria-experienced vaccinees exceeded those in malaria-naive vaccinees (mean 40.6 versus 16.1 micrograms ml-1; p = 0.005) as well as those induced by previous CS protein-derived vaccines and observed in association with natural infections. A log-rank comparison of time to falciparum malaria revealed no differences between vaccinated and non-vaccinated subjects. Secondary analyses revealed that CS antibody levels were lower in vaccinee malaria cases than in non-cases, 3 and 5 months after the third dose of vaccine (p = 0.06 and p = 0.014, respectively). Because antibody levels had fallen substantially before peak malaria transmission occurred, the question of whether high levels of CS antibody are protective remains to be resolved.", "The first objective of the study was to determine whether there is a relationship between the measles-mumps-rubella (MMR) vaccination and autism in children. The second objective was to examine whether the risk of autism differs between use of MMR and the single measles vaccine.\n Case-control study.\n The 96 cases with childhood or atypical autism, aged 2 to 15, were included into the study group. Controls consisted of 192 children individually matched to cases by year of birth, sex, and general practitioners.\n Data on autism diagnosis and vaccination history were from physicians. Data on the other probable autism risk factors were collected from mothers. Logistic conditional regression was used to assess the risk of autism resulting from vaccination. Assessment was made for children vaccinated (1) Before diagnosis of autism, and (2) Before first symptoms of autism onset. Odds ratios were adjusted to mother's age, medication during pregnancy, gestation time, perinatal injury and Apgar score.\n For children vaccinated before diagnosis, autism risk was lower in children vaccinated with MMR than in the nonvaccinated (OR: 0.17, 95% CI: 0.06-0.52) as well as to vaccinated with single measles vaccine (OR: 0.44, 95% CI: 0.22-0.91). The risk for vaccinated versus nonvaccinated (independent of vaccine type) was 0.28 (95% CI: 0.10-0.76). The risk connected with being vaccinated before onset of first symptoms was significantly lower only for MMR versus single vaccine (OR: 0.47, 95% CI: 0.22-0.99).\n The study provides evidence against the association of autism with either MMR or a single measles vaccine.", "Concern that measles-mumps-rubella (MMR) vaccination might cause autism has led to a fall in vaccine coverage. We investigated whether MMR vaccination is associated with an increased risk of autism or other pervasive developmental disorders.\n We did a matched case-control study using the UK General Practice Research Database. Cases were people born in 1973 or later who had first recorded diagnosis of pervasive developmental disorder while registered with a contributing general practice between 1987 and 2001. Controls were matched on age, sex, and general practice.\n 1294 cases and 4469 controls were included. 1010 cases (78.1%) had MMR vaccination recorded before diagnosis, compared with 3671 controls (82.1%) before the age at which their matched case was diagnosed. After adjustment for age at joining the database, the odds ratio for association between MMR and pervasive developmental disorder was 0.86 (95% CI 0.68-1.09). Findings were similar when restricted to children with a diagnosis of autism, to those vaccinated with MMR before the third birthday, or to the period before media coverage of the hypothesis linking MMR with autism.\n Our findings suggest that MMR vaccination is not associated with an increased risk of pervasive developmental disorders.", "To address the claim that the Leningrad-Zagreb (L-Z) mumps vaccine strain is causally associated with aseptic meningitis, a prospective, post-marketing safety study was conducted with a measles-mumps-rubella vaccine (MMR) (TRESIVAC(R); Serum Institute of India Ltd., Pune, India), which uses the L-Z strain as its mumps component in Egypt. In all, 453 119 children (65 423 children aged 16-24 months and 329 211 children aged 5-7 years) received MMR. The control groups which, as a result of local health regulations, were slightly younger than vaccinees, comprised 12 253 and 46 232 children, respectively. Using questionnaires, the parents recorded solicited local, systemic and neurological adverse events for up to 42 days post-vaccination. All data were analysed externally on an intention-to-treat basis by individuals not participating in the study. Local and/or systemic reactions were reported in a small percentage of participants, with pain, fever and parotitis being the most common signs among vaccinees in both age groups. No case of aseptic meningitis, encephalitis, anaphylaxis or convulsions was observed in any participant. Thus, in this series of more than 450 000 Egyptian children, the L-Z mumps vaccine strain in this vaccine did not cause aseptic meningitis. The vaccine is considerably cheaper than Western competitors and a valid alternative to other MMR vaccines.", "The suggestion that multi-antigen vaccines might overload the immune system has led to calls for single antigen vaccines. In 2003 we showed that rather than an increase there appeared to be a reduced risk of severe bacterial infection in the three months following Measles, Mumps and Rubella vaccine (MMR). The present analysis of illnesses in a general population is based on an additional 10 years of data for bacterial infections and also includes admissions with viral infections. Analyses were carried out using the self-controlled case-series method and separately for bacterial and viral infection cases, using risk periods of 0-30 days, 31-60 days and 61-90 days post MMR vaccine. An analysis was also carried out for those cases which were given MMR and Meningococcal serogroup C (MCC) vaccines concomitantly. A reduced risk was seen in the 0-30-day period for both bacterial infection (relative incidence=0.68, 95% CI 0.54-0.86) and viral infections (relative incidence=0.68, 95% CI 0.49-0.93). There was no increased risk in any period when looking at combined viral or bacterial infections or for individual infections with the single exception of an increased risk in the 31-60 days post vaccination period for herpes infections (relative incidence=1.69, 95% CI 1.06-2.70). For the children given Meningococcal group C vaccines concomitantly no significantly increased risk was seen in either the bacterial (relative incidence=0.54, 95% CI 0.26-1.13) or viral cases (relative incidence=0.46, 95% CI 0.11-1.93). Our study confirms that the MMR vaccine does not increase the risk of invasive bacterial or viral infection in the 90 days after the vaccination and does not support the hypothesis that there is an induced immune deficiency due to overload from multi-antigen vaccines.", "A randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the safety, reactogenicity and the immunogenicity of a 2 x 10(9)CFU dose of the 638 lyophilized live attenuated cholera vaccine for oral administration, formulated and produced at Finlay Institute, City of Havana, Cuba. Thirty-six healthy female and male adult volunteers from 18 to 40 years old were involved, clinically examined and laboratory tested after the informed consent signature. Adverse events were monitored and seroconversion rates and geometrical mean titer (GMT) of vibriocidal antibodies were tested in volunteer's sera samples. Neither serious adverse events nor other damages to the volunteers due to vaccine or placebo feeding were reported during the clinical follow-up period of this study; none of the adverse events registered within the first 72 h after inoculation were life-threatening for volunteers. Neither severe nor moderate adverse events were reported. Sixty-one percent of subjects showed mild expected adverse events in an interval lower than 24h up to the first 72 h, 75% of these in the vaccinated group and 18% in the placebo group. Fourteen days after inoculation the GMT of vibriocidal antibodies in the vaccine group significantly increased in comparison to the placebo group. All subjects in the vaccine group (24) seroconverted (100%). Results show that this vaccine is safe, well tolerated and immunogenic in healthy female and male volunteers.", "We conducted a double-blind, placebo-controlled, randomized crossover study to evaluate the safety and immunogenicity of a single 5 x 10(8)-CFU dose of live oral recombinant cholera vaccine CVD 103-HgR in 94 North American adults. The vaccine was well tolerated without associated adverse reactions. Despite minimal fecal excretion of vaccine, 97% of subjects exhibited serum vibriocidal antibody and 72% had antitoxin responses.", "To provide accurate information on the common sequelae of measles-mumps-rubella (MMR) vaccination and to compare post-vaccine symptoms in children vaccinated at 13 and 15 months.\n Prospective cluster randomized controlled trial.\n Twenty-two family practices in southwestern Ontario.\n All 376 infants who were due to receive MMR vaccine in the next year, 253 (67.3%) successfully completed the study.\n MMR vaccine administered at 13 months by half of the family physicians and at 15 months by the remaining half.\n Family physician's physical findings in children 7 days and 30 days after vaccine; reported illnesses by mothers in a daily diary in the month before and after vaccination and medical records of visits to family physicians and hospital admissions in the month before and after vaccination.\n Compared with the incidence rates in the corresponding weeks before vaccination, the rates of lymphadenopathy (23.8%) and fever (16.8%) were higher 1 week afterward and the rate of rash (26.9%) was higher 7 to 14 days afterward. Fewer health problems were reported in the third and fourth weeks after vaccination than in the corresponding weeks beforehand. Hospital admissions after vaccination were no more frequent than those before once cause and time of admission were taken into account. The two age groups did not differ in any of the outcomes.\n Mothers should be informed about the possibility of increased physical findings in the weeks after MMR vaccination, especially lymphadenopathy, nasal discharge and rash. Since the occurrence of sequelae does not seem to differ significantly between 13-month-old recipients and 15-month-old recipients, it should not influence the decision of when to administer the vaccine.", "Measles-mumps-rubella (MMR) vaccines containing the Urabe strain of mumps were withdrawn in the United Kingdom in 1992 following demonstration of an increased risk of aseptic meningitis 15-35 days after vaccination. Following introduction of a replacement MMR vaccine (Priorix; GlaxoSmithKline, London, United Kingdom) in 1998, active surveillance of aseptic meningitis and convulsion was established to evaluate the risk associated with the new vaccine. No laboratory-confirmed cases of mumps meningitis were detected among children aged 12-23 months after administration of 1.6 million doses of Priorix (upper 95% confidence limit of risk: 1:437,000) in England and Wales. The upper 95% confidence limit excluded the risk found for mumps meningitis with Urabe vaccines (1:143,000 doses). No cases of aseptic meningitis were detected among children aged 12-23 months, who had received over 99,000 doses of Priorix (upper 95% confidence limit of risk: 1:27,000), in a regional database of hospital-admitted cases. This compares with an observed risk of 1:12,400 for Urabe vaccines. An elevated relative incidence of convulsion was found in the 6- to 11-day period after receipt of Priorix (relative incidence = 6.26, 95% confidence interval: 3.85, 10.18)-consistent with the known effects of the measles component of MMR vaccine-but not in the 15- to 35-day period (relative incidence = 1.48, 95% confidence interval: 0.88, 2.50) as occurred with Urabe-containing vaccines. This study demonstrates the power of active postmarketing surveillance to identify or exclude events too rare to be detected in prelicensure trials.", "A single dose (5 x 10(8) organisms) of attenuated A- B+ Vibrio cholerae classical Inaba recombinant vaccine strain CVD 103-HgR or placebo was administered to 24 healthy young Thai adults in a randomized, placebo-controlled, double-blind trial of safety and immunogenicity. None of the volunteers experienced untoward reactions. The vaccine strain was recovered from 2 of 12 vaccines. The vibriocidal antibody response (the best immunological correlate of protection) was good: 11 of 12 vaccinees (92%) manifested significant serotype-homologous Inaba antibody rises with a peak reciprocal geometric mean titer (RGMT) postvaccination of 3,417; 9 of 12 exhibited significant serotype-heterologous Ogawa antibody rises (prevaccination RGMT, 180; peak RGMT, 2,874). Nine of 12 vaccinees had significant rises in serum antitoxin. None of the controls exhibited rises in vibriocidal or antitoxic antibody. This preliminary study further confirms the safety and immunogenicity of CVD 103-HgR live oral cholera vaccine and paves the way for larger community studies of this candidate cholera vaccine.", "The safety and effectiveness of a Vero cell-derived inactivated Japanese encephalitis (JE) vaccine were compared with those of a current JE vaccine in non-clinical studies and a phase I clinical trial. The single-dose toxicity study showed no toxicity of either the current JE vaccine or the investigational Vero cell-derived JE vaccine. In a local irritation study, the degree of irritation caused by both vaccines was determined to be the same as that induced by normal saline. To investigate genotoxicity, a chromosomal aberration test was conducted and the results were negative. Both JE vaccines were administered to a group of 30 subjects who were seronegative (neutralizing antibody titer <10(1)) for JEV virus (Beijing-1 Strain). Each subject was subcutaneously inoculated twice at an interval of 1-4 weeks, followed by an additional booster inoculation 4-8 weeks later, and clinical reactions and serological responses were subsequently investigated. Adverse drug reactions of local reaction, headache and malaise were mild, occurring at a rate of 6.7 and 20.0% after administration of the Vero cell-derived JE vaccine and the current JE vaccine, respectively. The seroconversion rate after three doses of both JE vaccines was 100%, while the geometric mean titer for the Vero cell-derived and current JE vaccines was 10(2.35) and 10(2.03), respectively. These results suggest that the safety and effectiveness of the Vero cell-derived inactivated JE vaccine are equal to those of the currently available conventional vaccine in humans, and that the Vero cell-derived vaccine could be a useful second-generation JE vaccine.", "Recombinant A-B+ Vibrio cholerae O1 strain CVD 103-HgR is a safe, highly immunogenic, single-dose live oral vaccine in adults in industrialized countries. Safety, excretion, immunogenicity, vaccine transmissibility, and environmental introduction of CVD 103-HgR were investigated among 24- to 59-month-old children in Jakarta. In 81 households, 1 child was randomly allocated a single dose of vaccine (5 x 10(9) cfu) and another, placebo. Additionally, 139 unpaired children were randomly allocated vaccine or placebo. During 9 days of follow-up, diarrhea or vomiting did not occur more often among vaccines than controls. Vaccine was minimally excreted and was isolated from no controls and from 1 (0.6%) of 177 unvaccinated family contacts. A 4-fold or higher rise in serum vibriocidal antibody was observed in 75% of vaccines (10-fold rise in geometric mean titer over baseline). Of 135 paired placebo recipients or household contacts, 5 had vibriocidal seroconversions. Moore swabs placed in sewers and latrines near 97 households failed to detect vaccine. These observations pave the way for a large-scale field trial of efficacy.", "A double-blind, placebo-controlled comparison of single component and combination measles, mumps, and rubella (HPV-77:DE-5 and RA 27/3) virus vaccines involving 502 young children was conducted. The rubella antibody response was similar with RA 27/3 rubella and measles-mumps-rubella (RA 27/3) vaccines, but was diminished with the combination vaccine that incorporated HPV-77:DE-5 rubella. There was no evidence of enhanced clinical reactivity with either of the measles-mumps-rubella vaccines.", "A Phase I safety and immunogenicity study with a three-component blood-stage malaria vaccine was conducted in adult male subjects living in an endemic area of Papua New Guinea. The preparations were recombinant proteins which corresponded to parts of the two merozoite surface proteins of Plasmodium falciparum (MSP1 and 2), and of the ring-infected erythrocyte surface antigen (RESA). The three proteins were emulsified with the adjuvant Montanide ISA720. Ten subjects were injected twice (four weeks apart) with the vaccine formulation and two with the adjuvant alone. Mild pain at the site of injection was reported by about half of the subjects but no systemic reaction related to the formulation occurred. There was a sharp rise in geometric mean stimulation index after the second dose compared to baseline for MSP1 and RESA, while the rise was small for MSP2. Geometric mean antibody titres increased for MSP1 during the study, whereas they hardly changed for MSP2 and RESA. The vaccine formulation was safe when used in an already immune population. The vaccine induced good cellular responses, especially for MSP1 and RESA. Boosting of humoral responses was weak, probably because of high baseline antibody levels.", "The aim of the present study was to examine the efficacy of postexposure vaccination with Varilrix in the household setting. A randomized, double-blind, placebo-controlled design was used. Twenty-two children received the varicella vaccine and 20, a placebo. The relative risk of developing varicella with a placebo compared with the vaccine was 1.1 (95% confidence interval 0.55-2.21). The risk of developing moderate to severe disease was eight times greater in the placebo group (RR=8), indicating an 80% protective effect against moderate/severe disease. The varicella vaccine Varilrix may not be effective in preventing varicella when administered after household exposure, although it is highly effective in ameliorating the disease in those who acquire it under these circumstances.", "A refrigerator-stable rotavirus (RV) vaccine that withstands gastric acid is anticipated to permit more widespread use of RV vaccine.\n We investigated for the first time in infants an oral, liquid formulation of G1 and G2 human bovine reassortant rotavirus vaccine (HRRV) with a new stabilizer/buffer (S/B) containing sucrose, sodium phosphate and sodium citrate.\n During 1997 through 1998, 731 healthy infants approximately 2 to 4 months of age were enrolled at 19 US sites to receive 3 HRRV or placebo doses approximately 6 to 8 weeks apart in a partially double blinded study. Infants were randomized to: (1) HRRV with no S/B but with prefeeding; (2) HRRV plus 1 of 3 different concentrations/volumes of S/B; or (3) placebo.\n No serious vaccine-related adverse experiences or intussusception cases were reported. No statistically significant differences were observed between vaccine and placebo recipients for fever (> or =38.1 degrees C) 0 to 7 days after any dose, irritability, vomiting or diarrhea incidence 0 to 42 days after any dose. Vaccine virus shedding among vaccine recipients was uncommon. Among S/B vaccine groups, proportions of infants with a > or =3-fold titer rise from baseline to Postdose 3 for G1 serum-neutralizing antibody (SNA), G2 SNA, WC3 SNA, serum anti-RV IgA, serum anti-RV IgG and stool anti-RV IgA were generally similar to those of the prefed non-S/B group.\n HRRV with a new S/B was generally well-tolerated; immunogenicity was generally similar to the prefed non-S/B group. No intussusception cases were reported, but the small sample size precluded a definitive conclusion. A large international clinical study is under way to address safety and efficacy of an S/B formulation of a pentavalent version of HRRV.", "RTS,S/AS02A is a pre-erythrocytic malaria vaccine candidate in which a portion of the circumsporozoite surface protein (CSP) of Plasmodium falciparum is genetically linked to hepatitis B surface antigen (HBsAg) coexpressed in yeast with unfused HBsAg. The resulting particulate antigen is formulated with the adjuvant system AS02A. We have initiated the paediatric clinical development of this vaccine by conducting two sequential Phase I studies in children: a study in older children (6--11 years), followed by a second study in younger children (1--5 years). In each study, a double-blind, randomised controlled, staggered, dose-escalation design was used to evaluate 10 microg RTS,S dose (10 microg RTS,S in 0.1mL AS02A), 25 microg dose (25 microg RTS,S in 0.25mL AS02A) and finally a 50 microg dose (50 microg RTS,S in 0.5mL AS02A) of the RTS,S/AS02A candidate malaria vaccine administered according to a 0-, 1- and 3-month vaccination schedule. Safety and reactogenicity were evaluated before moving to a higher dose level. The RTS,S/AS02A vaccine was safe at all dose levels, in both age groups. No serious adverse events related to vaccination were reported. The frequency of local Grade 3 symptoms was low but tended to increase with increasing dose level. Grade 3 general adverse events in the RTS,S/AS02A groups were infrequent and of short duration. The majority of local and general Grade 3 symptoms resolved or decreased in intensity within 48h. The pattern and intensity of reactogenicity seen in these studies are similar to those of previous studies with RTS,S/AS02A. All doses were highly immunogenic for anti-CSP and anti-HBsAg antibodies. The pooled anti-CSP antibody data from the two studies showed that the 25 microg dose and 50 microg dose anti-CSP antibody response were similar at both dose levels. However, the immunogenicity of the 10 microg dose anti-CSP response was significantly lower than that of either the 50 microg or 25 microg dose. The 25 microg dose was selected for future studies of RTS,S/AS02A in paediatric populations.", "Two clinical studies were conducted to identify the optimal dose of a modified tick-borne encephalitis (TBE) vaccine (FSME-IMMUN \"new\") in adults. A prospective, randomised, phase II, double-blind dose-finding study with the FSME-IMMUN \"new\" vaccine was performed in volunteers aged 16-65 years (n=405) to evaluate the immunogenicity and safety of two vaccinations with three vaccine doses (0.6, 1.2 and 2.4microg antigen). The safety and immunogenicity of the third vaccination were investigated in a follow-up study on the same study population. Antibody response to vaccination was assessed by enzyme-linked immunosorbent assay (ELISA) and, after the third vaccination, by neutralisation test (NT). Seroconversion rates (ELISA) in the different dose groups (0.6, 1.2 and 2.4 microg) were 85.1, 96.2 and 97.0%, respectively, after the second vaccination, which 73% of the volunteers received only 21 days after the first vaccination. Seroconversion rates after the third vaccination were 96, 99.2 and 100% (ELISA) as well as 77, 93 and 96.6% (NT) with the 0.6, 1.2 and 2.4 microg doses, respectively. No unexpected AEs or vaccine-related serious adverse events (SAE) were observed during either study. Local and systemic reactions were mainly mild and not dose-dependent, with an overall fever rate of <1% after the first vaccination. The 2.4 microg dose is the optimal dose for the FSME-IMMUN \"new\" preparation in adults, as it was found to: (1) be non-inferior to the 1.2 microg dose with respect to fever rate after the first vaccination; (2) induce the highest seroconversion rate; and (3) be well-tolerated with respect to local and systemic reactions. The results of both studies demonstrate that the FSME-IMMUN \"new\" vaccine is safe and highly immunogenic in adults.", "Poxviral vectors have a proven safety record and can be used to incorporate multiple transgenes. Prior clinical trials with poxviral vaccines have shown that immunologic tolerance to self-antigens can be broken. Carcinoembryonic antigen (CEA) and MUC-1 are overexpressed in a substantial proportion of common solid carcinomas. The primary end point of this study was vaccine safety, with immunologic and clinical responses as secondary end points.\n We report here a pilot study of 25 patients treated with a poxviral vaccine regimen consisting of the genes for CEA and MUC-1, along with a triad of costimulatory molecules (TRICOM; composed of B7.1, intercellular adhesion molecule 1, and lymphocyte function-associated antigen 3) engineered into vaccinia (PANVAC-V) as a prime vaccination and into fowlpox (PANVAC-F) as a booster vaccination.\n The vaccine was well tolerated. Apart from injection-site reaction, no grade > or =2 toxicity was seen in more than 2% of the cycles. Immune responses to MUC-1 and/or CEA were seen following vaccination in 9 of 16 patients tested. A patient with clear cell ovarian cancer and symptomatic ascites had a durable (18-month) clinical response radiographically and biochemically, and one breast cancer patient had a confirmed decrease of >20% in the size of large liver metastasis.\n This vaccine strategy seems to be safe, is associated with both CD8 and CD4 immune responses, and has shown evidence of clinical activity. Further trials with this agent, either alone or in combination with immunopotentiating and other therapeutic agents, are warranted.", "Antigen-specific mucosal immunity is thought to be important for protection against influenza virus infection. Currently licensed parenteral influenza vaccines stimulate the production of serum antibodies, but are poor inducers of mucosal immunity. The adjuvant MF59 has been shown to enhance the humoral immune response to parenteral influenza vaccine in humans and the mucosal immune response to intranasally-administered influenza vaccine in mice. We conducted an open-label safety study followed by an observer-blind, randomized trial comparing the immune response to intranasally-administered subunit influenza vaccine adjuvanted with MF59, unadjuvanted subunit influenza vaccine, and placebo. Adverse reactions did not occur significantly more frequently in vaccinees than placebo recipients. Of 31 subjects receiving 2 doses of MF59-adjuvanted influenza vaccine, 19 (61%), 8 (26%), and 11 (35%) developed a mucosal IgA response to influenza A/H1N1, A/H3N2, and B, respectively. The percentage of subjects with a serum antibody response was slightly lower. The immune responses to adjuvanted vaccine were not significantly different from those to unadjuvanted vaccine. Both vaccines gave more frequent responses than seen in placebo recipients, indicating the potential of intranasal inactivated vaccines to stimulate local IgA responses.", "A live oral Vibrio cholerae O1 El Tor vaccine candidate, Peru-15, was studied for safety, immunogenicity, and excretion in phase 1 (inpatient) and phase 2 (outpatient) studies of Bangladeshi adults.METHODs. The study was conducted among adults, by use of a double-blind, randomized, placebo-controlled design. A single dose of Peru-15 (approximately 2 x 108 cfu) or placebo (buffer only) was given in standard bicarbonate and ascorbic acid buffer.RESULTS. Study treatment did not elicit any major adverse events in the volunteers, during either the inpatient or the outpatient phases, and there were no reports of diarrhea. V. cholerae was isolated from the stool of only 1 volunteer and was found to be genetically identical to the vaccine strain. Vibriocidal antibody responses were seen in 30 (75%) of 40 vaccine recipients and in 3 (10%) of 30 placebo recipients. Peripheral blood immunoglobulin (Ig) A and IgM antibody-secreting cell responses to lipopolysaccharide were seen in the majority of vaccine recipients (response rate, 78%--88%). Seroconversion for lipopolysaccharide-specific IgA antibodies was seen in 88% of vaccine recipients. The response in vaccine recipients was significantly higher than that in placebo recipients, in all of the immunological assays (P=.036 to <.001). A lower immunological response against cholera toxin B subunit was detected.CONCLUSIONS. The safety and immunogenicity of this Peru-15 vaccine candidate indicates the usefulness of future studies in Bangladesh, where cholera is endemic.", "The authors evaluated the association between receipt of measles-mumps-rubella (MMR) vaccine and asthma-like disease in early childhood in a Danish nationwide cohort study (N = 871,234). Two outcomes were included: hospitalizations with asthma diagnoses and use of anti-asthma medications (for a subset of the cohort only). Poisson regression was used to estimate rate ratios according to vaccination status. MMR-vaccinated children were less often hospitalized with an asthma diagnosis (rate ratio (RR) = 0.75, 95% confidence interval (CI): 0.73, 0.78) and used fewer courses of anti-asthma medication (RR = 0.92, 95% CI: 0.91, 0.92) than unvaccinated children. This \"protective\" effect of MMR vaccine was more pronounced for hospitalizations with severe asthma diagnoses (status asthmaticus: RR = 0.63, 95% CI: 0.49, 0.82) and use of medication that was highly specific for asthma (long-acting beta2-agonist inhalant: RR = 0.68, 95% CI: 0.63, 0.73). MMR vaccine was not negatively associated with anti-asthma medications often used for wheezing illnesses in early childhood (systemic beta2-agonist: RR = 1.02, 95% CI: 1.01, 1.02). These results are compatible not with an increased risk of asthma following MMR vaccination but rather with the hypothesis that MMR vaccination is associated with a reduced risk of asthma-like disease in young children.", "Nine participants with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, who were human leukocyte antigen (HLA)-A1, HLA-A2, or HLA-A3, were eligible to enroll in a phase 1 study designed to assess the safety and immunogenicity of a peptide-based vaccine. Participants received 5 class I major histocompatibility complex-restricted synthetic peptides derived from multiple ovarian cancer-associated proteins plus a class II major histocompatibility complex-restricted synthetic helper peptide derived from tetanus toxoid protein. The vaccines were administered with granulocyte macrophage-colony stimulating factor in Montanide ISA-51 adjuvant over a 7-week period. All vaccine-related toxicities were grade 1 to 2, the most common being injection site reaction (grade 2, 100%), fatigue (grade 1, 78%), and headache (grade 1, 67%). Lymphocytes from the peripheral blood and a node draining a secondary vaccine site (sentinel immunized node) were harvested during the course of vaccination and T-cell responses to the peptides were evaluated using an enzyme-linked immunosorbent spot assay. CD8 T-cell responses were detected in 1 participant ex vivo and in 8 of 9 participants (89%) after in vitro stimulation. All 4 HLA-A2 and HLA-A3-restricted peptides were immunogenic. This includes 2 peptides, folate binding protein (FBP191-199) and Her-2/neu754-762, which had not previously been evaluated in vaccines in humans. Responding T cells required over 200 nM for half-maximal reactivity. These data support continued investigation of these peptides as immunogens for patients with ovarian cancer but, owing to low potency, also suggest a need for additional immunomodulation in combination with vaccines to increase the magnitude and to improve the quality of the T-cell responses.", "CVD 103-HgR is a live oral cholera vaccine strain constructed by deleting 94% of the gene for the enzymatically active A subunit of cholera toxin from classical Inaba Vibrio cholerae O1 569B; the strain also contains a mercury resistance gene as an identifying marker. This vaccine was well tolerated and immunogenic in double-blind, controlled studies and was protective in open-label studies of volunteers challenged with V. cholerae O1. A randomized, double-blind, placebo-controlled, multicenter study of vaccine efficacy was designed to test longer-term protection of CVD 103-HgR against moderate and severe El Tor cholera in U.S. volunteers. A total of 85 volunteers (50 at the University of Maryland and 35 at Children's Hospital Medical Center/University of Cincinnati) were recruited for vaccination and challenge with wild-type V. cholerae El Tor Inaba. Volunteers were randomized in a double-blind manner to receive, with buffer, a single oral dose of either CVD 103-HgR (2 x 10(8) to 8 x 10(8) CFU) or placebo (killed E. coli K-12). About 3 months after immunization, 51 of these volunteers were orally challenged with 10(5) CFU of virulent V. cholerae O1 El Tor Inaba strain N16961, prepared from a standardized frozen inoculum. Ninety-one percent of the vaccinees had a >/=4-fold rise in serum vibriocidal antibodies after vaccination. After challenge, 9 (39%) of the 23 placebo recipients and 1 (4%) of the 28 vaccinees had moderate or severe diarrhea (>/=3-liter diarrheal stool) (P < 0.01; protective efficacy, 91%). A total of 21 (91%) of 23 placebo recipients and 5 (18%) of 28 vaccinees had any diarrhea (P < 0.001; protective efficacy, 80%). Peak stool V. cholerae excretion among placebo recipients was 1.1 x 10(7) CFU/g and among vaccinees was 4.9 x 10(2) CFU/g (P < 0.001). This vaccine could therefore be a safe and effective tool to prevent cholera in travelers.", "A prospective, randomised, multicentre, single-blind phase 3 study was performed to assess the safety of a vaccination schedule consisting of two vaccinations (21-35 days apart) with the tick-borne encephalitis (TBE) vaccine FSME-IMMUN \"adults\" (five consecutive lots) in comparison to another licensed TBE vaccine (Encepur), with polygeline) (two lots) in healthy volunteers (n=3966) aged 16-65 years. The safety of the third vaccination with FSME-IMMUN \"adults\" (6 months after the first vaccination) was investigated in a follow-up study on the same population (n=3705) and TBE antibody titres were analysed pre- and post-vaccination in a subgroup of volunteers (n=564). Following the first vaccination, the overall incidence of fever (> or =38.0 degrees C) was 0.8% in the FSME-IMMUN \"adults\" study group and 5.6% in the comparator study group; fever was mainly mild. The fever rate after the second vaccination was 0.6% and 0.5% in the two study groups, respectively. Local and systemic reactions after the first vaccination occurred with a lower frequency in the FSME-IMMUN \"adults\" study group than in the comparator group. Upon analysing the tolerability of the third vaccination with FSME-IMMUN \"adults\", similar results were determined in both study groups of volunteers previously vaccinated with FSME-IMMUN \"adults\" or with the comparator vaccine. The immunogenicity results demonstrated similar seroconversion rates (as determined by ELISA or neutralization test) before and after the third vaccination in the FSME-IMMUN \"adults\" group and in the comparator group respectively. The results of both studies demonstrate that: (1) FSME-IMMUN \"adults\" is safe and highly immunogenic, (2) all five production lots of FSME-IMMUN \"adults\" were consistent with respect to a low rate of adverse events, (3) FSME-IMMUN \"adults\" induces considerably lower adverse reaction rates than the comparator vaccine after the first vaccination, and (4) two vaccinations with the comparator vaccine can be successfully followed by a third vaccination with FSME-IMMUN \"adults\".", "Immunization of normal children and adults with Oka strain live varicella vaccine from several manufacturers has been studied in our laboratory and elsewhere. This paper summarizes clinical trials designed to obtain information on minimum dose immunogenicity pre- and postexposure prophylaxis, immunization of various age groups, and booster immunizations for seropositive individuals. These studies documented a 94% to 100% seroconversion rate with 95% to 100% persistence of antibodies at 3 to 4 years. Protective efficacy was more than 90%, and the vaccine was successful in preventing varicella when a high dose was given postexposure. Clinical reactions were limited to temperature elevations and minor papulovesicular rashes that occurred in 5% to 10% of vaccinees. Herpes zoster has been absent in vaccinated healthy individuals.", "Despite numerous therapeutic modalities reported in the literature, treatment of common warts remains a continuing challenge and there is no universal consensus about optimal treatment. Recently, intralesional immunotherapy by different antigens has proved efficacy in the treatment of different types of warts.\n To evaluate the efficacy and safety of intralesional mumps, measles and rubella (MMR) vaccine in the treatment of common warts.\n The study included 135 patients with single or multiple recalcitrant or non-recalcitrant common warts. They were randomly assigned to two groups; the first group (85 patients) received intralesional MMR vaccine, and the second group (50 patients) received intralesional saline as a control group. Both treatments were injected into single lesions or largest wart in case of multiple lesions at 2-week intervals until complete clearance or for a maximum of five treatments. Follow-up was made every 2 months for 6 months to detect any recurrence.\n A highly significant difference was found between the therapeutic response of common warts to MMR vaccine and saline control group (P < 0.001). In the MMR group, complete response was achieved in 80% and 84.6% of patients presenting with recalcitrant and multiple warts respectively. No recurrence was observed in the MMR group and side effects included pain during injection and flu-like symptoms.\n Intralesional immunotherapy by MMR vaccine is a promising effective and safe treatment modality for common warts, particularly the multiple ones.\n © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.", "The short-term safety of an effective and inexpensive new live attenuated Japanese encephalitis vaccine (SA14-14-2) was studied in a randomized trial, using block randomization. Of 26,239 children who were enrolled, half received the vaccine and half served as controls. Subjects were prospectively followed for 30 days for severe adverse events, such as encephalitis, meningitis, and \"all-cause\" hospitalization. No cases of encephalitis or meningitis occurred in either group. The upper 95% confidence limit for adverse events not occurring among subjects receiving their first dose was 4.1/10,000. Risk ratios and 95% confidence intervals for other adverse events were 0.70 (0.43-1.15) for all-cause hospitalization, 0.91 (0.37-2.22) for seizure, and 0.79 (0.56-1.11) for fever lasting > or = 3 days. These data attest to the short-term safety of the SA14-14-2 virus strain and the hamster kidney cell substrate.", "A causal relationship between the measles, mumps, and rubella (MMR) vaccine and occurrence of autism spectrum disorders (ASD) has been claimed, based on an increase in ASD in the USA and the UK after introduction of the MMR vaccine. However, the possibility that this increase is coincidental has not been eliminated. The unique circumstances of a Japanese MMR vaccination program provide an opportunity for comparison of ASD incidence before and after termination of the program.\n This study examined cumulative incidence of ASD up to age seven for children born from 1988 to 1996 in Kohoku Ward (population approximately 300,000), Yokohama, Japan. ASD cases included all cases of pervasive developmental disorders according to ICD-10 guidelines.\n The MMR vaccination rate in the city of Yokohama declined significantly in the birth cohorts of years 1988 through 1992, and not a single vaccination was administered in 1993 or thereafter. In contrast, cumulative incidence of ASD up to age seven increased significantly in the birth cohorts of years 1988 through 1996 and most notably rose dramatically beginning with the birth cohort of 1993.\n The significance of this finding is that MMR vaccination is most unlikely to be a main cause of ASD, that it cannot explain the rise over time in the incidence of ASD, and that withdrawal of MMR in countries where it is still being used cannot be expected to lead to a reduction in the incidence of ASD.", "Many malaria vaccines are currently in development, although very few have been evaluated for efficacy in the field. Plasmodium falciparum multiple epitope (ME)- thrombospondin-related adhesion protein (TRAP) candidate vaccines are designed to potently induce effector T cells and so are a departure from earlier malaria vaccines evaluated in the field in terms of their mechanism of action. ME-TRAP vaccines encode a polyepitope string and the TRAP sporozoite antigen. Two vaccine vectors encoding ME-TRAP, plasmid DNA and modified vaccinia virus Ankara (MVA), when used sequentially in a prime-boost immunisation regime, induce high frequencies of effector T cells and partial protection, manifest as delay in time to parasitaemia, in a clinical challenge model.\n A total of 372 Gambian men aged 15-45 y were randomised to receive either DNA ME-TRAP followed by MVA ME-TRAP or rabies vaccine (control). Of these men, 296 received three doses of vaccine timed to coincide with the beginning of the transmission season (141 in the DNA/MVA group and 155 in the rabies group) and were followed up. Volunteers were given sulphadoxine/pyrimethamine 2 wk before the final vaccination. Blood smears were collected weekly for 11 wk and whenever a volunteer developed symptoms compatible with malaria during the transmission season. The primary endpoint was time to first infection with asexual P. falciparum. Analysis was per protocol. DNA ME-TRAP and MVA ME-TRAP were safe and well-tolerated. Effector T cell responses to a non-vaccine strain of TRAP were 50-fold higher postvaccination in the malaria vaccine group than in the rabies vaccine group. Vaccine efficacy, adjusted for confounding factors, was 10.3% (95% confidence interval, -22% to +34%; p = 0.49). Incidence of malaria infection decreased with increasing age and was associated with ethnicity.\n DNA/MVA heterologous prime-boost vaccination is safe and highly immunogenic for effector T cell induction in a malaria-endemic area. But despite having produced a substantial reduction in liver-stage parasites in challenge studies of non-immune volunteers, this first generation T cell-inducing vaccine was ineffective at reducing the natural infection rate in semi-immune African adults.", "Incidence and severity of herpes zoster (HZ) and postherpetic neuralgia increase with age, associated with age-related decrease in immunity to varicella-zoster virus (VZV). One dose of zoster vaccine (ZV) has demonstrated substantial protection against HZ; this study examined impact of a second dose of ZV.\n Randomized, double-blind, multicenter study with 210 subjects ≥60 years old compared immunity and safety profiles after one and two doses of ZV, separated by 6 weeks, vs. placebo. Immunogenicity was evaluated using VZV interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assay and VZV glycoprotein enzyme-linked immunosorbent antibody (gpELISA) assay. Adverse experiences (AEs) were recorded on a standardized Vaccination Report Card.\n No serious vaccine-related AEs occurred. VZV IFN-γ ELISPOT geometric mean count (GMC) of spot-forming cells per 10(6) peripheral blood mononuclear cells increased in the ZV group from 16.9 prevaccination to 49.5 and 32.8 at 2 and 6 weeks postdose 1, respectively. Two weeks, 6 weeks and 6 months postdose 2, GMC was 44.3, 42.9, and 36.5, respectively. GMC in the placebo group did not change during the study. The peak ELISPOT response occurred ∼2 weeks after each ZV dose. The gpELISA geometric mean titers (GMTs) in the ZV group were higher than in the placebo group at 6 weeks after each dose. Correlation between the IFN-γ ELISPOT and gpELISA assays was poor.\n ZV was generally well-tolerated and immunogenic in adults ≥60 years old. A second dose of ZV was generally safe, but did not boost VZV-specific immunity beyond levels achieved postdose 1.\n Copyright © 2011 Elsevier Ltd. All rights reserved.", "To compare the safety and immunogenicity of Lederle Laboratories' (Pearl River, NY) diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine with diphtheria and tetanus toxoids and whole-cell pertussis (DTwP) vaccine when administered simultaneously with measles-mumps-rubella (MMR) vaccine and trivalent oral poliovirus (OPV) vaccine at 15 to 16 months of age.\n Randomized and double-blind.\n Two general pediatric practices.\n Ninety-seven infants, aged 15 to 16 months, who had received three previous DTwP immunizations. SELECTION PROCEDURES AND INTERVENTIONS: Healthy children received the DTaP or DTwP vaccine. Infants received the MMR vaccine at a separate site and the OPV vaccine concurrently. Blood was obtained on day 0 and at 6 weeks. Adverse events were recorded by parents at specified times after immunization.\n Within 3 days of immunization, DTaP vaccine recipients had less fever, drowsiness, and irritability (P = .01, .04, .01, respectively). They also experienced less tenderness, erythema, and induration (.001, .001, and .002, respectively). There was no difference in the frequency of adverse reactions 6 to 14 days after immunization. Enzyme-linked immunosorbent assays were used to determine all antibody values. Antibody responses to filamentous hemagglutinin and pertussis toxoid were significantly greater in the DTaP group (P = .0001 and .02, respectively). Immune responses to the other measured antigens were similar.\n Simultaneous administration of the Lederle DTaP with MMR and OPV vaccines did not interfere with antibody response to pertussis antigens measured or measles, mumps, or rubella viruses and was associated with fewer local and systemic adverse events during the first 3 days following immunization when compared with the simultaneous administration of the DTwP, OPV, and MMR vaccines. We conclude that the DTaP vaccine can be administered at 15 months of age concurrently with the MMR and OPV vaccines.", "We undertook an epidemiological study to investigate whether measles, mumps, and rubella (MMR) vaccine may be causally associated with autism.\n Children with autism born since 1979 were identified from special needs/disability registers and special schools in eight North Thames health districts, UK. Information from clinical records was linked to immunisation data held on the child health computing system. We looked for evidence of a change in trend in incidence or age at diagnosis associated with the introduction of MMR vaccination to the UK in 1988. Clustering of onsets within defined postvaccination periods was investigated by the case-series method.\n We identified 498 cases of autism (261 of core autism, 166 of atypical autism, and 71 of Asperger's syndrome). In 293 cases the diagnosis could be confirmed by the criteria of the International Classification of Diseases, tenth revision (ICD10: 214 [82%] core autism, 52 [31%] atypical autism, 27 [38%] Asperger's syndrome). There was a steady increase in cases by year of birth with no sudden \"step-up\" or change in the trend line after the introduction of MMR vaccination. There was no difference in age at diagnosis between the cases vaccinated before or after 18 months of age and those never vaccinated. There was no temporal association between onset of autism within 1 or 2 years after vaccination with MMR (relative incidence compared with control period 0.94 [95% CI 0.60-1.47] and 1.09 [0.79-1.52]). Developmental regression was not clustered in the months after vaccination (relative incidence within 2 months and 4 months after MMR vaccination 0.92 [0.38-2.21] and 1.00 [0.52-1.95]). No significant temporal clustering for age at onset of parental concern was seen for cases of core autism or atypical autism with the exception of a single interval within 6 months of MMR vaccination. This appeared to be an artifact related to the difficulty of defining precisely the onset of symptoms in this disorder.\n Our analyses do not support a causal association between MMR vaccine and autism. If such an association occurs, it is so rare that it could not be identified in this large regional sample.", "A newly formulated, oral, inactivated whole cell plus recombinant B subunit (WC/rBS) cholera vaccine was evaluated in US military personnel. In the first study, 74 subjects were given two doses 14 days apart. In the second study, 186 subjects were randomized into four groups; two groups received vaccine with either full (4 g) or half (2 g) strength bicarbonate buffer, and two groups received either full or half strength buffer without vaccine. Mild gastrointestinal symptoms were associated with full buffer (P = .02) but not with the vaccine. In the first study, 36% of all subjects and 55% with low prevaccination titers (< 1:40) had a > or = 2-fold rise in vibriocidal antibody level; > 80% of subjects developed a 4-fold rise in anti-cholera toxin (CT) titers. Post-vaccination IgA and IgG anti-CT titers were approximately 1.5-fold higher among persons receiving full strength buffer (P = .05). The WC/rBS vaccine is safe and immunogenic in North Americans, although some mild gastrointestinal symptoms occur with the high concentration of buffer necessary to protect the B subunit from gastric acid denaturation. Prior immunity to cholera conferred by parenteral vaccine decreased vibriocidal antibody response.", "Effective, safe antimalarial vaccines have proved elusive. The synthetic polypeptide SPf66 vaccine is based on preerythrocytic and asexual blood-stage proteins of Plasmodium falciparum. We report here a randomised double-blind placebo-controlled trial of the efficacy of the SPf66 vaccine against clinical P falciparum malaria in idete, southern Tanzania, an area of intense perennial malaria transmission. 586 children aged 1-5 years received three doses of vaccine (n = 274) or placebo (n = 312). The incidence and density of parasitaemia were assessed through repeated cross-sectional surveys on subgroups of children. Morbidity was monitored over a 1 year period through passive case detection in all children plus active case detection in a subgroup of 191. An episode of clinical malaria was defined as measured fever (> or = 37.5 degrees C) and parasite density > 20,000/microL. No severe side-effects were seen and the frequency of mild side-effects after the third dose was less than 6%. The vaccine was highly immunogenic and after three doses all vaccine recipients had detectable anti-SPf66 antibodies: the geometric mean index of response was 8.3 in the vaccine group and 0.7 in the placebo group. The incidence of parasitaemia was similar in both groups. 123 children had at least one episode of clinical malaria during the follow-up period after the third dose and annual incidence rates were 0.25 in the vaccine group and 0.35 in the placebo group. Estimated vaccine efficacy was 31% (95% confidence interval 0-52%; p = 0.046). After the third dose there were 6 deaths among the study cohort (1 vaccine, 5 placebo). This study confirms that SPf66 is safe, immunogenic and reduces the risk of clinical malaria among children exposed to intense P falciparum transmission.", "A phase II safety and immunogenicity study of an oral-formalin inactivated enterotoxigenic Escherichia coli (ETEC) vaccine containing six colonization factors (CFA/I, CS1, CS2, CS3, CS4, CS5) and 1mg of recombinant cholera toxin B subunit (the CF-BS-ETEC vaccine) was carried out in an urban slum of Dhaka city in Bangladesh. The study was carried out in a double blinded, placebo controlled design in 158 children, 18-36 months of age. Children were given two doses of the CF-BS-ETEC vaccine or the placebo which consisted of E. coli K12. The vaccine was well tolerated. The immune response was studied in 60 children (30 each in the placebo and vaccine group). Significant vaccine specific IgA antibody-secreting cell (ASC) responses were seen 7 days after ingestion of the first and second dose of the vaccine. The responses to CFA/I (P<or=0.001), CS2 (P=0.021), CS4 (P=0.009) and rCTB (P<or=0.001) were elevated in the vaccines in comparison to the pre-immune values and in comparison to those seen in the placebo recipients (P=0.018 to <0.001). Vaccines but not placebo recipients also showed significantly increased IgM ASC responses to all three CF antigens that were tested (P=0.012 to <0.001) and IgG-ASCs to rCTB (P<0.001). Peak ASC levels were reached after one dose of the vaccine with no further increase or decrease after the second dose. The vaccine recipients also responded with IgA plasma antibodies to CFA/I, CS1, CS2, CS4 and rCTB after one or two doses of the vaccine (P=0.01 to <0.001). Subjects in the placebo group failed to mount responses to any of the antigens. The vaccine also induced responses in mucosal IgA antibodies in feces to CFA/I, CS2 and rCTB (61, 88 and 69% responder frequency, respectively) and the magnitude of the response was elevated in comparison to the pre-immune levels (P=0.031 to <0.001) and to the levels of the control group (P=0.003 to <0.001). This study thus shows that the CF-BS-ETEC vaccine is well tolerated in children, 18-36 months of age and gives rise to significant systemic and mucosal IgA antibody responses.", "Efficacy and side effects following the immunization with Salmonella typhi Vi capsular polysaccharide vaccine (Vi) were assessed. The diluted solution (DS) of Vi was used as placebo. A total number of 777 children and adults were observed for side effect response. Mild and moderate fever appeared 16.93% and 0.05% in Vi group, 15.01% and 0.03% in DS group, respectively (statistically significant). Two cases with mild local reaction were observed in Vi group. A total number of 81,506 vaccinees were investigated on the efficacy of Vi vaccine, using positive blood culture of Salmonolla typhi as a diagnostic criterion. The protective rate and index of vaccine were 71.35% and 3.49% respectively. If 2 cases of positive Widal's test were included in, the protective rate would come up to 78.17% with a protective index 4.85. Clinical data showed that fever seen in the cases in Vi group was much lower than that of DS group. The systematic and local reaction of Vi vaccine were mild. The vaccine is safe and has high protective rate. It can also decrease the degree of fever with only one single dose as primary immunization. We believe Vi vaccine may serve as a vaccine of new generation to be promoted.", "Serum responses to oral cholera vaccines were assessed in three paediatric vaccine trials, two in León, Nicaragua and one in Stockholm, Sweden. A calibrated anti-cholera toxin B subunit (CTB) IgA ELISA was used together with an assay for vibriocidal antibodies. Swedish children had lower pre-vaccination levels of antibody, but serum responses were more pronounced in Swedish children than in Nicaraguan children. Post-vaccination levels of anti-toxin antibody were generally above those found after natural infections with enterotoxigenic Escherichia coli, that cross-reacts serologically with Vibrio cholerae. Adverse events seen after vaccination were generally mild and of little clinical significance.", "Despite considerable experience with single-dose, live, oral cholera vaccine CVD 103-HgR in Asia, Europe, and the Americas, the vaccine had not been evaluated in sub-Saharan Africa or on individuals infected with human immunodeficiency virus (HIV). We therefore conducted a randomized, placebo-controlled, double-blind, cross-over clinical trial in 38 HIV-seropositive (without clinical acquired immunodeficiency syndrome (AIDS)) and 387 HIV-seronegative adults in Mali to assess its safety and immunogenicity. Adverse reactions (fever, diarrhoea and vomiting) were observed with similar frequency among vaccine and placebo recipients. The vaccine strain was not isolated from the coprocultures of any subject. The baseline geometric mean titre (GMT) of serum vibriocidal antibody was significantly lower in HIV-seropositives (1:23) than in HIV-seronegatives (1:65) (P = 0.002). Significant rises in vibriocidal antibody were observed in 71% of HIV-seronegatives and 58% of HIV-seropositives, and in 40% of HIV-seropositives with CD4+ counts below 500 per microliter. Following immunization, the peak vibriocidal GMT in HIV-seronegatives was 1:584 versus 1:124 in HIV-seropositives (P = 0.0006); in HIV-seropositives with CD4+ counts < 500 per microliter, the peak vibriocidal GMT was 1:40 (P = 0.03 versus other HIV-seropositives). CVD 103-HgR was safe in HIV-infected Malian adults, although serological responses were significantly attenuated among HIV-seropositives (particularly in those with CD4+ counts < 500 per microliter) relative to HIV-seronegatives. These results encourage further evaluations of this single-dose, oral cholera vaccine in high-risk populations such as refugees in sub-Saharan Africa.", "Double-blind controlled cholera-vaccine trials were carried out in rural East Pakistan in 1963 and 1964. Pretrial studies indicated that a whole-cell cholera vaccine of high mouse protective potency, at a dose of 0.5 ml, produced an antibody response and reaction pattern consistent with use in such trials. A purified Ogawa antigen, given at a dose of 100 mug, elicited no adverse reactions and evoked both agglutinating and vibriocidal antibodies against both Inaba and Ogawa test suspensions.In the field, adverse reactions to the cholera vaccines occurred primarily among adults and were observed with both the whole-cell preparation and the purified Ogawa antigen. At the dose used in the field trials (0.4 ml), the reactions elicited by the whole-cell vaccine were acceptable to the population and no more marked than those following the locally prepared typhoid-paratyphoid vaccine. Delayed reactions to the whole-cell cholera vaccine were observed beginning 4 to 7 days after the vaccine was administered; the bulk of them (60%) did not interfere with work at any time; all resolved promptly; and none developed fluctuation or was associated with abscess formation.", "Whole-cell pertussis (wP) and measles vaccines are effective in preventing disease but have also been suspected of increasing the risk of encephalopathy or encephalitis. Although many countries now use acellular pertussis vaccines, wP vaccine is still widely used in the developing world. It is therefore important to evaluate whether wP vaccine increases the risk of neurologic disorders.\n A retrospective case-control study was performed at 4 health maintenance organizations. Records from January 1, 1981, through December 31, 1995, were examined to identify children aged 0 to 6 years old hospitalized with encephalopathy or related conditions. The cause of the encephalopathy was categorized as known, unknown or suspected but unconfirmed. Up to 3 controls were matched to each case. Conditional logistic regression was used to analyze the relative risk of encephalopathy after vaccination with diphtheria-tetanus-pertussis (DTP) or measles-mumps-rubella (MMR) vaccines in the 90 days before disease onset as defined by chart review compared with an equivalent period among controls indexed by matching on case onset date.\n Four-hundred fifty-two cases were identified. Cases were no more likely than controls to have received either vaccine during the 90 days before disease onset. When encephalopathies of known etiology were excluded, the odds ratio for case children having received DTP within 7 days before onset of disease was 1.22 (95% confidence interval [CI] = 0.45-3.31, P = 0.693) compared with control children. For MMR in the 90 days before onset of encephalopathy, the odds ratio was 1.23 (95% confidence interval = 0.51-2.98, P = 0.647).\n In this study of more than 2 million children, DTP and MMR vaccines were not associated with an increased risk of encephalopathy after vaccination.", "RTS,S/AS02 is a pre-erythrocytic malaria vaccine based on the circumsporozoite surface protein of Plasmodium falciparum fused to HBsAg, incorporating a new adjuvant (AS02). We did a randomised trial of the efficacy of RTS,S/AS02 against natural P. falciparum infection in semi-immune adult men in The Gambia.\n 306 men aged 18-45 years were randomly assigned three doses of either RTS,S/AS02 or rabies vaccine (control). Volunteers were given sulfadoxine/pyrimethamine 2 weeks before dose 3, and kept under surveillance throughout the malaria transmission season. Blood smears were collected once a week and whenever a volunteer developed symptoms compatible with malaria. The primary endpoint was time to first infection with P. falciparum. Analysis was per protocol.\n 250 men (131 in the RTS,S/AS02 group and 119 in the control group) received three doses of vaccine and were followed up for 15 weeks. RTS,S/AS02 was safe and well tolerated. P. falciparum infections occurred significantly earlier in the control group than the RTS,S/AS02 group (Wilcoxon's test p=0.018). Vaccine efficacy, adjusted for confounders, was 34% (95% CI 8.0-53, p=0.014). Protection seemed to wane: estimated efficacy during the first 9 weeks of follow-up was 71% (46-85), but decreased to 0% (-52 to 34) in the last 6 weeks. Vaccination induced strong antibody responses to circumsporozoite protein and strong T-cell responses. Protection was not limited to the NF54 parasite genotype from which the vaccine was derived. 158 men received a fourth dose the next year and were followed up for 9 weeks; during this time, vaccine efficacy was 47% (4-71, p=0.037).\n RTS,S/AS02 is safe, immunogenic, and is the first pre-erythrocytic vaccine to show significant protection against natural P. falciparum infection.", "In October 1988 combined measles, mumps and rubella (MMR) vaccination replaced monocomponent measles as part of the routine childhood vaccination programme in the United Kingdom. Prior to this policy change a study was undertaken in 335 children aged 15 months, to evaluate the clinical reactions and immunogenicity of the new combined MMR vaccine (Trimovax, Immravax, Merieux), in comparison with an established monocomponent measles vaccine (Rouvax, Merieux). Parents were asked to select whether their child should receive MMR vaccine or measles monocomponent; over 95% chose MMR. Children who were given the MMR vaccine had seroconversion rates of 96% for measles, 97% for mumps and 100% for rubella, whilst those who received monocomponent measles vaccine had a seroconversion rate of 100%. The number of side effects reported was similar with both vaccines; all were mild and self-limiting. The results from this study confirm the efficacy and low reactogenicity of MMR vaccine and support its use as part of the routine childhood immunisation programme in the United Kingdom.", "The immunogenicity and safety of a new liquid hexavalent vaccine (diphtheria-tetanus-acellular pertussis-inactivated polio vaccine-hepatitis B-polyribosyl ribitol phosphate conjugated to tetanus protein; Hexavac; Aventis Pasteur MSD, Lyon, France) are compared with those of reference vaccines [diphtheria-tetanus-acellular pertussis-inactivated polio vaccine reconstituting lyophilized purified Haemophilus influenzae polysaccharide conjugated to tetanus protein vaccine (Pentavac; Aventis Pasteur MSD) and hepatitis B vaccine (H-B-Vax II; Aventis Pasteur MSD)] injected separately at the same visit in a prospective multicenter, comparative, open label trial.\n Infants were randomized to receive Hexavac (n = 423) or Pentavac and H-B-Vax II (n = 425) as a primary immunization series at 2, 4 and 6 months of age. Seroprotection and seroconversion rates against all antigens at 1 month after the primary series were compared between the two vaccine groups with 95% confidence intervals (CI0.95) and were considered clinically equivalent (not inferior) when the upper limit of the 95% confidence interval on the difference (reference, hexavalent) was below predefined differences.\n Hexavac met and surpassed the pre-defined criteria for clinical equivalence to Pentavac and H-B-Vax II given concomitantly. It elicited similar seroprotection and seroconversion rates against all antigens. Seroprotection and seroconversion rates obtained 1 month after the third dose of Hexavac were >90% for all antigens. The postimmunization antibody geometric mean titers (GMT) for hepatitis B and purified Haemophilus influenzae polysaccharide were about 2-fold higher in infants who received the reference vaccines than in infants who had received Hexavac. GMTs for poliovirus antibodies tended to be enhanced in infants vaccinated with Hexavac. GMTs for all other antigens were very similar among both groups. Hexavac was generally well-tolerated. At least one local reaction was reported in 20.3% of Hexavac injections compared with 15.8% at the Pentavac injections site and 3.8% at the H-B-Vax II injections site. These reactions were generally mild and transient. At least one systemic adverse event was reported in 45.7% of Hexavac injections compared with 42.2% of Pentavac and H-B-Vax II injections (mild fever, irritability and drowsiness were most frequently reported). The frequency of adverse events was not significantly different between groups. No vaccine-related serious adverse event occurred during the study.\n This liquid hexavalent vaccine was generally well-tolerated and provided immune responses adequate to be protective against six infectious diseases with a single injection, given at 2, 4 and 6 months of age.", "Data from routine surveillance during two mass immunisation campaigns (MIC) with Measles-mumps-rubella (MMR)vaccine using Leningrad-Zagreb mumps strain in two states in Brazil were analysed to estimate the risk of vaccine-related meningitis and mumps. Increase in the incidence of the two diseases was observed in both states, 3 weeks after the vaccination campaigns. The estimated number of doses applied per one case of vaccine-related meningitis ranged from 6199 (95% CI: 4854-8058) to 19,247 (95% CI: 12,648-29,513) depending on the diagnostic criteria used and state. It was 300 doses (95% CI: 286-317) for each case of mumps. The implications for vaccination policy are discussed.", "To conduct a phase 1 safety and tolerability trial of an oral rotavirus vaccine candidate RV3 in healthy volunteers.\n Double blind placebo controlled trial of a single 1 mL oral dose (6.5 x 10(5) fluorescing focus units [FFU]/mL) in 10 healthy young men, 10 3-4 year old children and 10 3 month old infants with a 4 week surveillance period. The study was undertaken at a children's hospital and nearby community in Melbourne, Australia.\n All subjects successfully completed the trial. There were no significant side-effects attributable to the vaccine preparation in any age group. No shedding of vaccine virus was detected by enzyme immunoassay. There was evidence of an immune response in serum and/or gut secretions in two of five vaccinees in each age group.\n RV3 rotavirus vaccine appears to be safe and well tolerated. Evidence of immunogenicity in some subjects after a single dose encourages further trials to determine immunogenicity after three doses, after reduction of viral dose, and without prior administration of buffer.", "Perinatal transmission of hepatitis B virus (HBV) contributes to the high prevalence of chronic infection in China and many other countries. In a placebo-controlled trial among 166 infants, the 12-month efficacy of active postexposure prophylaxis to prevent chronic perinatal HBV infection varied by vaccine (range, 45%-89%). In a 5-year follow-up study, 2 additional infants became chronically infected with HBV, and the efficacy of active prophylaxis was estimated to be 38% and 72% for the two vaccines at 5 years. In addition, 80% of immunized infants continued to have protective levels of antibody at the end of 5 years. However, among 27 infants who received passive-active immunoprophylaxis with high-dose hepatitis B immune globulin, only 60% (11/19) had protective antibody levels. These data indicate that active postexposure immunization initiated soon after birth continues to provide protection during early childhood when there is a high risk of chronic HBV infection.", "MMR vaccine has been reported to cause gait disturbance, and this possible association has been claimed to support the MMR-causes-autism theory.\n To determine whether any association between gait disturbance and MMR vaccination exceeds the age related background rate of gait disturbance, using record linkage and self control case series analyses.\n MMR vaccination records were linked to hospital admission and general practitioner attendance data. An increased rate of gait problems with onset in various intervals in the 60 day period after MMR vaccination was looked for in children aged 12 to <24 months.\n No evidence of an increased rate of hospital admission or general practice consultations for gait disturbance was found in the putative post-vaccination risk periods.\n This study provides no evidence for a causal association between MMR and gait disturbance.", "The vaccine (NANP)3-TT is a synthetic peptide of the circumsporozoite protein (CS) of Plasmodium falciparum coupled to tetanus toxoid (TT) as protein carrier and adsorbed to aluminium hydroxide as adjuvant. The objectives of the study were to assess the immunogenicity and the protective efficacy of the vaccine in an area where malaria is endemic. The study was conducted in a zone of irrigated rice cultivation known as the Vallée du Kou to the North of Bobo-Dioulasso. Malaria transmission is permanent in the Vallée with maxima in July and November. The study was conducted from June to December 1988. It was a controlled randomised, double blind, prospective vaccine trial. A total of 123 infants from 3 to 5 months of age were randomly assigned to three groups. Group I (controls) received three doses of TT alone, group II received two doses of TT and one of (NANP)3-TT and group III received three doses of (NANP)3-TT. These vaccines were administered simultaneously with the Enlarged Program of Immunisation (EPI) vaccines. The clinical parasitological and immunological status of the children was then monitored over a period of five months. No systemic reactions to the vaccine were observed in the infants either immediately after administration or during the follow-up. Minor local tumefactions were observed in only 3% of the children. The vaccine was found to be immunogenic with a peak IgG response at day 75, when 56% (group II) and 60% (group III) showed antibody titres of at least four times that seen at day 0. The response, however, was a short duration; by day 150 the average antibody titres were not significantly different between the three groups. The incidence and the level of parasiaemia and the incidence of clinical malaria were also not significantly different for each of the three groups during the period of the study. The association of (NANP)3 with tetanus toxoid was not shown to be immunologically inhibitive. The results, despite not showing a protective effect for the vaccine (NANP)3-TT, have shown its immunogenicity and therefore suggest that further development of this vaccine may be worthwhile.", "A randomized, double-blind, placebo controlled trial was conducted in 50 healthy Swiss adults to assess the safety and immunogenicity of the live oral attenuated cholera vaccine candidate strain Vibrio cholerae CVD 103-HgR (classical, Inaba). A single dose of 5 x 10(8) viable CVD 103-HgR organisms, administered in a buffered liquid formulation, was well tolerated as compared with individuals who received an equivalent amount of heat-killed Escherichia coli K-12 placebo. Eighty-eight percent of subjects receiving CVD 103-HgR mounted a significant (greater than fourfold) rise in Inaba vibriocidal titre while 68% did so for the heterologous Ogawa serotype. The magnitude of the vibriocidal antibody response (as measured by peak geometric mean titre and by fold-rise in titre over baseline) was greater for the homologous Inaba serotype. Nineteen out of 25 volunteers (76%) responded with a significant (p less than 0.05) rise in serum antitoxin levels. No vaccinee who received the E. coli K-12 placebo mounted a significant rise in either vibriocidal or antitoxin antibody levels. These results corrobrate the safety and immunogenicity of CVD 103-HgR in healthy adult volunteers.", "The malaria vaccine Combination B comprises recombinant Plasmodium falciparum ring-infected erythrocyte surface antigen and 2 merozoite surface proteins (MSP1 and MSP2) formulated in oil-based adjuvant. A phase 1-2b double-blind, randomized, placebo-controlled trial in 120 children (5-9 years old) in Papua New Guinea demonstrated a 62% (95% confidence limits: 13%, 84%) reduction in parasite density in children not pretreated with sulfadoxine-pyrimethamine. Vaccinees had a lower prevalence of parasites carrying the MSP2-3D7 allelic form (corresponding to that in the vaccine) and a higher incidence of morbid episodes associated with FC27-type parasites. These results demonstrate functional activity of Combination B against P. falciparum in individuals with previous malaria exposure. The specific effects on parasites with particular msp2 genotypes suggest that the MSP2 component, at least in part, accounted for the activity. The vaccine-induced selection pressure exerted on the parasites and its consequences for morbidity strongly argue for developing vaccines comprising conserved antigens and/or multiple components covering all important allelic types.", "In 1999, the US Congress directed the Centers for Disease Control and Prevention to conduct a pivotal safety and efficacy study of anthrax vaccine adsorbed (AVA).\n To determine the effects on serological responses and injection site adverse events (AEs) resulting from changing the route of administration of AVA from subcutaneous (s.q.) to intramuscular (i.m.) and omitting the week 2 dose from the licensed schedule.\n Assessment of the first 1005 enrollees in a multisite, randomized, double-blind, noninferiority, phase 4 human clinical trial (ongoing from May 2002).\n Healthy adults received AVA by the s.q. (reference group) or i.m. route at 0, 2, and 4 weeks and 6 months (4-SQ or 4-IM; n = 165-170 per group) or at a reduced 3-dose schedule (3-IM; n = 501). A control group (n = 169) received saline injections at the same time intervals.\n Noninferiority at week 8 and month 7 of anti-protective antigen IgG geometric mean concentration (GMC), geometric mean titer (GMT), and proportion of responders with a 4-fold rise in titer (%4 x R). Reactogenicity outcomes were proportions of injection site and systemic AEs.\n At week 8, the 4-IM group (GMC, 90.8 microg/mL; GMT, 1114.8; %4 x R, 97.7) was noninferior to the 4-SQ group (GMC, 105.1 microg/mL; GMT, 1315.4; %4 x R, 98.8) for all 3 primary end points. The 3-IM group was noninferior for only the %4 x R (GMC, 52.2 microg/mL; GMT, 650.6; %4 x R, 94.4). At month 7, all groups were noninferior to the licensed regimen for all end points. Solicited injection site AEs assessed during examinations occurred at lower proportions in the 4-IM group compared with 4-SQ. The odds ratio for ordinal end point pain reported immediately after injection was reduced by 50% for the 4-IM vs 4-SQ groups (P < .001). Route of administration did not significantly influence the occurrence of systemic AEs.\n The 4-IM and 3-IM regimens of AVA provided noninferior immunological priming by month 7 when compared with the 4-SQ licensed regimen. Intramuscular administration significantly reduced the occurrence of injection site AEs. Trial Registration clinicaltrials.gov Identifier: NCT00119067.", "In order to evaluate the safety and immunogenicity of domestic produced lyophilized recombinant, B-subunit, inactivated whole cell vaccine of vibrio cholerae (rBS-WC), 369 subjects were randomly divided into three groups and observed with masking method, one with high dose of vaccine (5 mg rBS and 10\" WC), another with low dose (1 mg rBS and 10\" WC), and the control one with placebo. Three doses of vaccine were given orally at an interval of seven days and 14 days, respectively. Results showed that only one subject had mild adverse reaction in the vaccine group (1/247) and none in the control group. Serum and fecal antibody conversion rates and average levels of antibodies in the two vaccine groups were significantly higher than those in control one. There was no significant difference in serum and fecal antibody conversion rate and average antibody levels between the two vaccine groups. But, antibody response was different among subjects of various sex, age, and vaccine doses. It indicates that rBS-WC vaccine of vibrio cholerae had good immunogenicity and safety." ]	The design and reporting of safety outcomes in MMR vaccine studies, both pre- and post-marketing, are largely inadequate. The evidence of adverse events following immunisation with the MMR vaccine cannot be separated from its role in preventing the target diseases.
CD007231	[ "15929052" ]	[ "Autologous mesenchymal stem cell transplantation in stroke patients." ]	[ "Mesenchymal stem cell (MSC) transplantation improves recovery from ischemic stroke in animals. We examined the feasibility, efficacy, and safety of cell therapy using culture-expanded autologous MSCs in patients with ischemic stroke. We prospectively and randomly allocated 30 patients with cerebral infarcts within the middle cerebral arterial territory and with severe neurological deficits into one of two treatment groups: the MSC group (n = 5) received intravenous infusion of 1 x 10(8) autologous MSCs, whereas the control group (n = 25) did not receive MSCs. Changes in neurological deficits and improvements in function were compared between the groups for 1 year after symptom onset. Neuroimaging was performed serially in five patients from each group. Outcomes improved in MSC-treated patients compared with the control patients: the Barthel index (p = 0.011, 0.017, and 0.115 at 3, 6, and 12 months, respectively) and modified Rankin score (p = 0.076, 0.171, and 0.286 at 3, 6, and 12 months, respectively) of the MSC group improved consistently during the follow-up period. Serial evaluations showed no adverse cell-related, serological, or imaging-defined effects. In patients with severe cerebral infarcts, the intravenous infusion of autologous MSCs appears to be a feasible and safe therapy that may improve functional recovery." ]	No large trials of stem cell transplantation have been performed in ischemic stroke patients and it is too early to know whether this intervention can improve functional outcome. Large, well-designed trials are needed.
CD005167	[ "12795572", "11018229", "15555694", "2136866", "12963672", "16582056", "9550248" ]	[ "Family-focused treatment versus individual treatment for bipolar disorder: results of a randomized clinical trial.", "Family-focused treatment of bipolar disorder: 1-year effects of a psychoeducational program in conjunction with pharmacotherapy.", "Does adjunctive family therapy enhance recovery from bipolar I mood episodes?", "A randomized clinical trial of inpatient family intervention. V. Results for affective disorders.", "A randomized study of family-focused psychoeducation and pharmacotherapy in the outpatient management of bipolar disorder.", "Cognitive-behavioural therapy for severe and recurrent bipolar disorders: randomised controlled trial.", "Effects of psychoeducational intervention for married patients with bipolar disorder and their spouses." ]	[ "Recently hospitalized bipolar, manic patients (N = 53) were randomly assigned to a 9-month, manual-based, family-focused psychoeducational therapy (n = 28) or to an individually focused patient treatment (n = 25). All patients received concurrent treatment with mood-stabilizing medications. Structured follow-up assessments were conducted at 3-month intervals for a 1-year period ofactive treatment and a 1-year period of posttreatment follow-up. Compared with patients in individual therapy, those in family-focused treatment were less likely to be rehospitalized during the 2-year study period. Patients in family treatment also experienced fewer mood disorder relapses over the 2 years, although they did not differ from patients in individual treatment in their likelihood of a first relapse. Results suggest that family psychoeducational treatment is a useful adjunct to pharmacotherapy in decreasing the risk of relapse and hospitalization frequently associated with bipolar disorder.", "Few studies have examined the combined effects of psychosocial treatment and pharmacotherapy for bipolar disorder. This study used a randomized, controlled design to examine a 9-month, manual-based program of family-focused psychoeducational treatment (FFT).\n Bipolar patients (N = 101) were recruited shortly after an illness episode and randomly assigned to 21 sessions of FFT (n = 31) or to a comparison treatment involving two family education sessions and follow-up crisis management (CM; n = 70). Both treatments were delivered over 9 months; patients were simultaneously maintained on mood stabilizing medications. Patients were evaluated every 3 months for 1 year as to relapse status, symptom severity, and medication compliance.\n Patients assigned to FFT had fewer relapses and longer delays before relapses during the study year than did patients in CM. Patients in FFT also showed greater improvements in depressive (but not manic) symptoms. The most dramatic improvements were among FFT patients whose families were high in expressed emotion. The efficacy of FFT could not be explained by differences among patients in medication regimes or compliance.\n Family-focused psychoeducational treatment appears to be an efficacious adjunct to pharmacotherapy for bipolar disorder. Future studies should evaluate family treatment against other forms of psychotherapy matched in amount of therapist-patient contact.", "Family therapy is sometimes used as adjunctive treatment to pharmacotherapy to help patients recover from mood episodes of bipolar I disorder. However, the efficacy of this practice is not known.\n Ninety-two patients meeting criteria for a current bipolar I mood episode were randomly assigned to family therapy plus pharmacotherapy, multifamily psychoeducational group therapy plus pharmacotherapy, or pharmacotherapy alone. Time to recovery was analyzed with survival analysis.\n The proportion of subjects within each treatment group who recovered did not significantly differ, nor did time to recovery.\n The analyses did not include other outcomes such as psychosocial functioning, prophylaxis against recurrences of mood episodes, or compliance with pharmacotherapy.\n Neither adjunctive family therapy nor adjunctive multifamily psychoeducational group therapy significantly improves the rate of recovery from mood episodes of bipolar I disorder, compared to treatment with pharmacotherapy alone.", "This paper reports the results at follow-up of a randomized clinical trial of combining family intervention with drug treatment during hospitalization for patients with affective disorder. The results suggest that female bipolar patients and their families benefited from family intervention, whereas unipolar patients and families did not. Patient outcome was positively correlated with the achievement of the goals of family intervention.", "Bipolar patients are at risk for relapses of their illness even when undergoing optimal pharmacotherapy. This study was performed to determine whether combining family-focused therapy (FFT) with pharmacotherapy during a postepisode interval enhances patients' mood stability during maintenance treatment.\n In a randomized controlled trial, 101 bipolar patients were assigned to FFT and pharmacotherapy or a less intensive crisis management (CM) intervention and pharmacotherapy. Outcome assessments were conducted every 3 to 6 months for 2 years. Participants (mean +/- SD age, 35.6 +/- 10.2 years) were referred from inpatient or outpatient clinics after onset of a manic, mixed, or depressed episode. FFT consisted of 21 sessions of psychoeducation, communication training, and problem-solving skills training. Crisis management consisted of 2 sessions of family education plus crisis intervention sessions as needed. Both protocols lasted 9 months. Patients received pharmacotherapy for 2 study years. Main outcome measures included time to relapse, depressive and manic symptoms, and medication adherence.\n Rates of study completion did not differ across the FFT (22/31, 71%) and CM groups (43/70, 61%). Patients undergoing FFT had fewer relapses (11/31, 35%) and longer survival intervals (mean +/- SD, 73.5 +/- 28.8 weeks) than patients undergoing CM (38/70, 54%; mean +/- SD, 53.2 +/- 39.6 weeks; hazard ratio, 0.38; 95% confidence interval, 0.20-0.75; P =.003; intent to treat). Patients undergoing FFT showed greater reductions in mood disorder symptoms and better medication adherence during the 2 years than patients undergoing CM.\n Combining family psychoeducation with pharmacotherapy enhances the postepisode symptomatic adjustment and drug adherence of bipolar patients.", "Efficacy trials suggest that structured psychological therapies may significantly reduce recurrence rates of major mood episodes in individuals with bipolar disorders.\n To compare the effectiveness of treatment as usual with an additional 22 sessions of cognitive-behavioural therapy (CBT).\n We undertook a multicentre, pragmatic, randomised controlled treatment trial (n=253). Patients were assessed every 8 weeks for 18 months.\n More than half of the patients had a recurrence by 18 months, with no significant differences between groups (hazard ratio=1.05; 95% CI 0.74-1.50). Post hoc analysis demonstrated a significant interaction (P=0.04) such that adjunctive CBT was significantly more effective than treatment as usual in those with fewer than 12 previous episodes, but less effective in those with more episodes.\n People with bipolar disorder and comparatively fewer previous mood episodes may benefit from CBT. However, such cases form the minority of those receiving mental healthcare.", "The relative benefit of adding a structured psychoeducational intervention to standard medication treatment for married patients with bipolar disorder and their spouses was assessed. Patients were randomly assigned to receive either medication management or medication management plus a marital intervention with their spouses for an 11-month period. Patients' symptoms, functioning, and adherence to their medication regimens were measured at study entry and at 11 months. Significant effects favoring the combined treatments were observed for overall patient functioning but not for symptom levels. The marital intervention was associated with improved medication adherence. Combined psychosocial and medication treatment does not affect patients' symptom levels beyond the effects of medication alone, but it does result in significant incremental gains in overall patient functioning." ]	To date there is only a small and heterogeneous body of evidence on the effectiveness of family oriented approaches for bipolar disorder, and it is not yet possible to draw any definite conclusions to support their use as an adjunctive treatment for bipolar disorder. Further well designed RCTs should be a research priority.
CD006352	[ "16062094", "6275811", "8161288", "7172160", "4571196" ]	[ "Risperidone, quetiapine, and fluphenazine in the treatment of patients with therapy-refractory schizophrenia.", "Fluphenazine vs placebo in patients with remitted, acute first-episode schizophrenia.", "Fluphenazine vs placebo supplementation for prodromal signs of relapse in schizophrenia.", "A double-blind comparison of fluspirilene and fluphenazine decanoate in schizophrenia.", "Outpatient maintenance of chronic schizophrenic patients with long-acting fluphenazine: double-blind placebo trial. Report to the Medical Research Council Committee on Clinical Trials in Psychiatry." ]	[ "This 12-week, double-blind study evaluated the effectiveness of risperidone (4 mg/day), quetiapine (400 mg/day), or fluphenazine (12.5 mg/day) in a stringently defined treatment-resistant population of people with schizophrenia. No differences were noted in total Brief Psychiatric Rating Scale (BPRS) or Clinical Global Impression scores among the drug groups (n = 38). More subjects tended to complete the study on risperidone (69%) or quetiapine (58%) than those treated with fluphenazine (31%; P value not significant). Eighty-nine percent of those who discontinued on fluphenazine (8 of 9) were due to lack of efficacy. Discontinuation due to adverse effects was low, with only 2 subjects (both on quetiapine) stopping due to side effects. Three of 13 risperidone-treated subjects (23%) and 3 of 12 quetiapine-treated subjects (25%) met response criteria (decrease of 20% of total BPRS score), whereas 2 of 13 subjects (15%) responded to fluphenazine. Side effect occurrence was similar among drug groups and EPS ratings on the Simpson Angus Scale improved in all drug groups (quetiapine, 1.64; risperidone, 1.30; fluphenazine, 0.69; P value not significant). Despite the newer class of second-generation antipsychotic medications, this treatment-resistant population remains difficult to treat. Many people have only minimal to modest improvements with antipsychotic treatment and most continue to have residual psychotic symptoms. Treatment with first- and second-generation antipsychotics may demonstrate similar efficacy; however, patients treated with second-generation antipsychotics may be more likely to adhere to treatment.", "Twenty-eight patients who had recently recovered from an acute-onset, first-episode schizophrenic illness were randomly given fluphenazine hydrochloride or decanoate or placebo for a one-year period in a double-blind study. Seven of 17 patients(14%) receiving placebo experienced a psychotic relapse, whereas none of 11 drug-treated patients experienced a relapse. Eighteen (69%) of the 26 patients available for follow-up (mean interval, 3.5 years) experienced a second psychotic relapse either during the study or afterward, and 50% (14/28) of the original sample experienced a third episode.", "We studied the effectiveness of treating patients with low doses of fluphenazine decanoate and supplementing them with oral fluphenazine when there was evidence of prodromal symptoms of psychotic exacerbations.\n Eighty schizophrenic patients who were receiving 5 to 10 mg of fluphenazine decanoate every 2 weeks were monitored for prodromal symptoms using an idiosyncratic prodromal rating scale. When patients met our criteria for a prodromal episode, they were randomly assigned to a double-blind comparison of oral fluphenazine hydrochloride (5 mg twice daily) or a placebo for the current and future prodromal episodes. We compared rates of psychotic exacerbations in the two treatment groups.\n Thirty-six patients (45%) met the criteria for a prodrome at some point during the trial and were randomized to drug or placebo. Using survival analysis during the entire 2 years, we did not find a significant difference between fluphenazine and placebo in the likelihood that a prodrome would continue to an exacerbation. Survival analysis beginning at the start of the second year of treatment did indicate a significant reduction in exacerbation risk for patients receiving drug supplementation (P = .032). Similarly, there was no difference between the two groups in the proportion of time at risk spent in exacerbation during the first year, but patients receiving active drug supplementation spent less time in an exacerbated state in the second year (P = .05).\n Our treatment strategy appeared to be effective for some patients, particularly those who were able to remain in the study beyond the first year. Although the occurrence of a prodrome was a fairly good marker that a patient was at high risk of ultimate exacerbation with our low-dose maintenance protocol, prodromes were not highly sensitive indicators of imminent exacerbation.", "A double-blind comparison of fluspirilene and fluphenazine decanoate in 28 schizophrenic patients over six months showed equal improvement and the same incidence of side-effects in each group of patients. It would be expected from the literature that a better ratio of therapeutic to side-effects would appear with fluspirilene than with fluphenazine. The absence of such an effect in this study may be attributable to an initial lack of familiarity by the investigators with the use of fluspirilene, indicating an important potential variable in the comparison of a new drug with an established one.", "A double-blind placebo trial of fluphenazine decanoate, a long-acting phenothiazine, was carried out to determine its value in maintenance therapy of chronic schizophrenic outpatients already established on the drug for a minimum period of eight weeks. In low doses it was significantly more effective than placebo in preventing relapse and admission to hospital. Relapse was accompanied by a resurgence of specifically schizophrenic symptoms and by an increase in abnormalities described by the relatives. There was no difference between the experimental and control groups in the treatment required for depression. The group on active medication required more treatment for Parkinsonism, but this difference did not reach statistical significance.In the context of a well-run special clinic for outpatient follow-up of chronic schizophrenic patients these results confirm the usefulness of long-acting fluphenazine. By inference, the benefit of this treatment highlights the need for adequate community services to deal with the residual chronic disabilities which are characteristic of these patients." ]	The findings in this review confirm much that clinicians and recipients of care already know, but they provide quantification to support clinical impression. Fluphenazine's global position as an effective treatment for psychoses is not threatened by the outcome of this review. However, fluphenazine is an imperfect treatment and If accessible, other inexpensive drugs less associated with adverse effects may be an equally effective choice for people with schizophrenia. The addition of seven studies to awaiting classification may alter the conclusions of this review once assessed.
CD004874	[ "21829969", "9690406", "17567657", "8584362", "15572814", "16816491", "18182412", "11853793", "7807627", "18177775", "15451221", "12975069", "17901791", "329949", "2903386", "2194687", "9814400", "15070633", "9057377", "11141388", "10768436", "8458247", "2863675", "15569557", "15702045" ]	[ "Antibiotic treatment schemes for very severe community-acquired pneumonia in children: a randomized clinical study.", "Antimicrobial resistance and clinical effectiveness of co-trimoxazole versus amoxycillin for pneumonia among children in Pakistan: randomised controlled trial. Pakistan Co-trimoxazole Study Group.", "Comparison of oral amoxicillin and intravenous benzyl penicillin for community acquired pneumonia in children (PIVOT trial): a multicentre pragmatic randomised controlled equivalence trial.", "A randomized trial of chloramphenicol vs. trimethoprim-sulfamethoxazole for the treatment of malnourished children with community-acquired pneumonia.", "Comparison of two antibiotic regimens in the empirical treatment of severe childhood pneumonia.", "Penicillin and gentamicin therapy vs amoxicillin/clavulanate in severe hypoxemic pneumonia.", "Chloramphenicol versus ampicillin plus gentamicin for community acquired very severe pneumonia among children aged 2-59 months in low resource settings: multicentre randomised controlled trial (SPEAR study).", "Chloramphenicol versus benzylpenicillin and gentamicin for the treatment of severe pneumonia in children in Papua New Guinea: a randomised trial.", "Trial of co-trimoxazole versus procaine penicillin G and benzathin penicillin + procaine penicillin G in the treatment of childhood pneumonia.", "Ambulatory short-course high-dose oral amoxicillin for treatment of severe pneumonia in children: a randomised equivalency trial.", "Oral amoxicillin versus injectable penicillin for severe pneumonia in children aged 3 to 59 months: a randomised multicentre equivalency study.", "[A comparison of moxifloxacin and amoxicillin in the treatment of community-acquired pneumonia in Latin America: results of a multicenter clinical trial].", "Comparative study of levofloxacin in the treatment of children with community-acquired pneumonia.", "Amoxycillin and co-trimoxazole in presumed viral respiratory infections of childhood: placebo-controlled trial.", "Trial of co-trimoxazole versus procaine penicillin with ampicillin in treatment of community-acquired pneumonia in young Gambian children.", "Randomized trial of sulfamethoxazole + trimethoprim versus procaine penicillin for the outpatient treatment of childhood pneumonia in Zimbabwe.", "Effectiveness of intramuscular penicillin versus oral amoxicillin in the early treatment of outpatient pediatric pneumonia.", "Three day versus five day treatment with amoxicillin for non-severe pneumonia in young children: a multicentre randomised controlled trial.", "Effectiveness of ampicillin and combination of penicillin and chloramphenicol in the treatment of pneumonias: randomized controlled trial.", "[Oral levofloxacin versus intravenous ceftriaxone and amoxicillin/clavulanic acid in the treatment of community-acquired pneumonia that requires hospitalization].", "An antibiotic policy to prevent emergence of resistant bacilli.", "Amoxycillin and clavulanic acid versus cefotaxime and metronidazole as antibiotic prophylaxis in elective colorectal resectional surgery.", "Chloramphenicol alone versus chloramphenicol plus penicillin for severe pneumonia in children.", "Comparative efficacy of amoxicillin, cefuroxime and clarithromycin in the treatment of community -acquired pneumonia in children.", "A randomized, multicenter, double blind, double dummy trial of single dose azithromycin versus high dose amoxicillin for treatment of uncomplicated acute otitis media." ]	[ "To compare clinical response to initial empiric treatment with oxacillin plus ceftriaxone and amoxicillin plus clavulanic acid in hospitalized children diagnosed with very severe community-acquired pneumonia (CAP).\n A prospective randomized clinical study was conducted among children 2 months to 5 years old with a diagnosis of very severe CAP in the pediatric ward of São Paulo State University Hospital in Botucatu, São Paulo, Brazil, from April 2007 to May 2008. Patients were randomly divided into two groups by type of treatment: an oxacillin/ceftriaxone group (OCG, n = 48) and an amoxicillin/clavulanic acid group (ACG, n = 56). Analyzed outcomes were: time to clinical improvement (fever and tachypnea), time on oxygen therapy, length of stay in hospital, need to widen antimicrobial spectrum, and complications (including pleural effusion).\n The two groups did not differ statistically for age, sex, symptom duration before admission, or previous antibiotic treatment. Time to improve tachypnea was less among ACG patients than OCG patients (4.8 ± 2.2 versus 5.8 ± 2.4 days respectively; P = 0.028), as was length of hospital stay (11.0 ± 6.2 versus 14.4 ± 4.5 days respectively; P = 0.002). There were no statistically significant differences between the two groups for fever improvement time, time on oxygen therapy, need to widen antimicrobial spectrum, or frequency of pleural effusion.\n Both treatment plans are effective in treating very severe CAP in 2-month-to 5-year-old hospitalized children. The only analyzed outcome that favored amoxicillin/clavulanic acid treatment was time required to improve tachypnea.\n ClinicalTrials.gov ID: NCT01166932.", "Co-trimoxazole is widely used in treatment of paediatric pneumonia in developing countries, but drug resistance may decrease its effectiveness. We studied the effectiveness of co-trimoxazole compared with that of amoxycillin in pneumonia therapy, and assessed the clinical impact of co-trimoxazole resistance.\n We recruited 595 children, aged 2-59 months, with non-severe or severe pneumonia (WHO criteria) diagnosed in the outpatient wards of two urban Pakistan hospitals. Patients were randomly assigned on a 2:1 basis co-trimoxazole (n=398) or amoxycillin (n=197) in standard WHO doses and dosing schedules, and were monitored in study wards. The primary outcome was inpatient therapy failure (clinical criteria) or clinical evidence of pneumonia at outpatient follow-up examination.\n There were 92 (23%) therapy failures in the co-trimoxazole group and 30 (15%) in the amoxycillin group (p=0.03)-26 (13%) versus 12 (12%) among children with non-severe pneumonia (p=0.856) and 66 (33%) versus 18 (18%) among those with severe pneumonia (p=0.009). For patients with severe pneumonia, age under 1 year (p=0.056) and positive chest radiographs (p=0.005) also predicted therapy failure. There was no significant association between antimicrobial minimum inhibitory concentration and outcome among bacteraemic children treated with co-trimoxazole.\n Co-trimoxazole provided effective therapy in non-severe pneumonia. For severe, life-threatening pneumonia, however, co-trimoxazole is less likely than amoxycillin to be effective.", "To ascertain whether therapeutic equivalence exists for the treatment of paediatric community acquired pneumonia by the oral and intravenous (IV) routes.\n A multicentre pragmatic randomised controlled non-blinded equivalence trial was undertaken in eight paediatric centres in England (district general and tertiary hospitals). Equivalence was defined as no more than a 20% difference between treatments of the proportion meeting the primary outcome measure at any time. 246 children who required admission to hospital and had fever, respiratory symptoms or signs and radiologically confirmed pneumonia were included in the study. Exclusion criteria were wheeze, oxygen saturations <85% in air, shock requiring >20 ml/kg fluid resuscitation, immunodeficiency, pleural effusion at presentation requiring drainage, chronic lung condition (excluding asthma), penicillin allergy and age <6 months. The patients were randomised to receive oral amoxicillin for 7 days (n = 126) or IV benzyl penicillin (n = 120). Children in the IV group were changed to oral amoxicillin after a median of six IV doses and received 7 days of antibiotics in total. The predefined primary outcome measure was time for the temperature to be <38 degrees C for 24 continuous hours and oxygen requirement to cease. Secondary outcomes were time in hospital, complications, duration of oxygen requirement and time to resolution of illness.\n Oral amoxicillin and IV benzyl penicillin were shown to be equivalent. Median time for temperature to settle was 1.3 days in both groups (p<0.001 for equivalence). Three children in the oral group were changed to IV antibiotics and seven children in the IV group were changed to different IV antibiotics. Median time to complete resolution of symptoms was 9 days in both groups.\n Oral amoxicillin is effective for most children admitted to hospital with pneumonia (all but those with the most severe disease who were excluded from this study). Prior to this study, the British Thoracic Society guidelines on childhood pneumonia could not draw on evidence to address this issue. This will spare children and their families the trauma and pain of cannulation, and children will spend less time in hospital.", "Children in developing countries who present with malnutrition often have infections, particularly pneumonia, at the time of presentation. We evaluated the initial antibiotic management of 144 Gambian children who presented for the first time with malnutrition and who had clinical or radiologic evidence of pneumonia. They were enrolled in a double blind trial of trimethoprim-sulfamethoxazole vs. chloramphenicol. Most children in the study underwent detailed investigations of bacterial and viral etiology as part of another study. The study drug was administered for a week along with oral metronidazole, vitamins and standardized nutritional therapy. Treatment failure was defined as the need for change to parenteral antibiotics during treatment, failure to respond to a week of treatment with the study drug or relapse during the following 2 weeks. There were no differences between the treatment groups in the clinical indicators of severity, etiology or radiologic findings. Thirty-three children were excluded from the analysis because of tuberculosis, inappropriate enrollment or inadequate follow-up. Of the 111 children remaining, 32 (16 in each arm of the study) failed treatment. Clinical failure was not related to in vitro antimicrobial resistance in the 20 cases in which invasive bacterial isolates were obtained. Those who failed treatment were more likely to have had lower chest wall indrawing and positive bacterial cultures than those who were successfully treated. In an area with infrequent antimicrobial resistance of common respiratory pathogens, oral chloramphenicol and trimethoprim-sulfamethoxazole were equally effective in the initial management of malnourished children with community-acquired pneumonia.", "The diagnosis and the treatment of community-acquired severe pneumonia is still a serious child health problem in developing countries. The aim of this study is to evaluate the effectiveness of two different antibiotic regimens in the empirical treatment of severe childhood pneumonia.\n We enrolled 97 infants (aged 2-24 months) with severe community-acquired pneumonia in a randomized-controlled trial of 10 days of treatment with penicillin G+chloramphenicol (n:46) or ceftriaxone (n:51). We evaluated the effectiveness of treatments with symptoms and some laboratory tests during and at the end of the study.\n The cure rates were similar in both groups and the antibiotic regimens in all patients were found effective (P< 0.001). The number of nurse rounds was much more in penicillin plus chloramphenicol group than ceftriaxone group.\n Both penicillin G plus chloramphenicol and ceftriaxone are effective in the empirical treatment of severe community pneumonia of young children. In spite of more nurse visits for antibiotic treatment, penicillin G+ chloramphenicol combination may be a cheaper alternative to ceftriaxone in the treatment of childhood pneumonia.", "To compare the efficacy of sequential injectable crystalline penicillin (C.pen) and gentamicin combination followed by oral amoxicillin with sequential IV and oral amoxicillin-clavulanate (amox-clav) in treatment of severe or very severe hypoxemic pneumonia.\n Children aged 2-59 months with WHO-defined severe or very severe pneumonia with hypoxemia (SpO2 < 90%) were included in the study. Patients with fever > 10 days, bacterial meningitis, prior antibiotic therapy > 24 hours, stridor, heart disease and allergy to any of the study drugs were excluded. They were randomly allocated to two groups--Group A and Group B. Group A received C. pen and gentamicin intravenously (IV), followed by oral amoxicillin and group B got amox-clav IV, followed by oral amox-clav. Minimum duration of IV therapy was 3 days and total 7 days. Respiratory rate, oxygen saturation and chest wall indrawing were monitored 6 hourly.\n 71 patients were included. There were two (5.2%) blood cultures positive in group A and three (9%) in group B. Organisms isolated were S. pneumoniae (n=3) and H. influenzae-b (n=2). There was only one treatment failure in each of the groups. One was due to penicillin resistant H. influenzae -b and the other was due to worsening of pneumonia. The mean time taken for normalization of tachypnea, hypoxia, chest wall indrawing and inability to feed was similar (P-N.S). Mean duration of IV therapy in group A was 76+/-25 hrs and group B was 75+/-24 hrs (p>0.1).\n In children of 2-59 months, sequential injectable C. pen and gentamicin combination, followed by oral amoxicillin or sequential IV and oral amox-clav were equally effective for the treatment of severe or very severe hypoxemic community acquired pneumonia.", "To evaluate whether five days' treatment with injectable ampicillin plus gentamicin compared with chloramphenicol reduces treatment failure in children aged 2-59 months with community acquired very severe pneumonia in low resource settings.\n Open label randomised controlled trial.\n Inpatient wards within tertiary care hospitals in Bangladesh, Ecuador, India, Mexico, Pakistan, Yemen, and Zambia.\n Children aged 2-59 months with WHO defined very severe pneumonia.\n Chloramphenicol versus a combination of ampicillin plus gentamicin.\n Primary outcome measure was treatment failure at five days. Secondary outcomes were treatment failure defined similarly among all participants evaluated at 48 hours and at 10 and 21 days.\n More children failed treatment with chloramphenicol at day 5 (16% v 11%; relative risk 1.43, 95% confidence interval 1.03 to 1.97) and also by days 10 and 21. Overall, 112 bacterial isolates were obtained from blood and lung aspirates in 110 children (11.5%), with the most common organisms being Staphylococcus aureus (n=47) and Streptococcus pneumoniae (n=22). In subgroup analysis, bacteraemia with any organism increased the risk of treatment failure at 21 days in the chloramphenicol group (2.09, 1.41 to 3.10) but not in the ampicillin plus gentamicin group (1.12, 0.59 to 2.13). Similarly, isolation of S pneumoniae increased the risk of treatment failure at day 21 (4.06, 2.73 to 6.03) and death (5.80, 2.62 to 12.85) in the chloramphenicol group but not in the ampicillin plus gentamicin group. No difference was found in treatment failure for children with S aureus bacteraemia in the two groups, but the power to detect a difference in this subgroup analysis was low. Independent predictors of treatment failure by multivariate analysis were hypoxaemia (oxygen saturation <90%), receiving chloramphenicol, being female, and poor immunisation status.\n Injectable ampicillin plus gentamicin is superior to injectable chloramphenicol for the treatment of community acquired very severe pneumonia in children aged 2-59 months in low resource settings.\n Current Controlled Trials ISRCTN39543942.", "Pneumonia is the most frequent cause of child mortality in less-developed countries. We aimed to establish whether the combination of benzylpenicillin and gentamicin or chloramphenicol would be better as first-line treatment in children with severe pneumonia in Papua New Guinea.\n We did an open randomised trial in which we enrolled children aged 1 month to 5 years of age who fulfilled the WHO criteria for very severe pneumonia and who presented to hospitals in two provinces. Children were randomly assigned to receive chloramphenicol (25 mg/kg 6 hourly) or benzylpenicillin (50 mg/kg 6 hourly) plus gentamicin (7.5 mg/kg daily) by intramuscular injection. The primary outcome measure was a good or an adverse outcome.\n 1116 children were enrolled; 559 children were treated with chloramphenicol and 557 with benzylpenicillin and gentamicin. At presentation the median haemoglobin oxygen saturation was 71% (IQR 57-77) for those allocated chloramphenicol and 69% (55-77) for those allocated penicillin and gentamicin. 147 (26%) children treated with chloramphenicol and 123 (22%) treated with penicillin and gentamicin had adverse outcomes (p=0.11). 36 children treated with chloramphenicol and 29 treated with penicillin and gentamicin died. More children treated with chloramphenicol than penicillin and gentamicin represented with severe pneumonia within 1 month of hospital discharge (p=0.03).\n For children with severe pneumonia in less-developed countries the probability of a good outcome is similar if treated with chloramphenicol or with the combination of benzylpenicillin and gentamicin.", "This study, which aimed to assess the results of three different regimens in the treatment of pneumonia, was carried out at the Pediatric Outpatient Department of Capa Children's Hospital in Istanbul on 151 patients aged between 4 months and 14 years. The first group (n = 46) received co-trimoxazole orally for 10 days and the second group (n = 63) procaine penicillin G in intramuscularly for 10 days. Benzathin penicillin G combined with procaine penicillin G was given to the third group (n = 42) as a single dose intramuscularly. While the best results were obtained with penicillin procaine G, no statistically significant difference was found between this regimen and co-trimoxazole therapy (chi 2 = 0.305023 P = 0.5). We suggest that co-trimoxazole is easy to administer and cost effective in the ambulatory treatment of pneumonia in children.", "WHO case management guidelines for severe pneumonia involve referral to hospital for treatment with parenteral antibiotics. If equally as effective as parenteral treatment, home-based oral antibiotic treatment could reduce referral, admission, and treatment costs. Our aim was to determine whether home treatment with high-dose oral amoxicillin and inpatient treatment with parenteral ampicillin were equivalent for the treatment of severe pneumonia in children.\n This randomised, open-label equivalency trial was done at seven study sites in Pakistan. 2037 children aged 3-59 months with severe pneumonia were randomly allocated to either initial hospitalisation and parenteral ampicillin (100 mg/kg per day in four doses) for 48 h, followed by 3 days of oral amoxicillin (80-90 mg/kg per day; n=1012) or to home-based treatment for 5 days with oral amoxicillin (80-90 mg/kg per day in two doses; n=1025). Follow-up assessments were done at 1, 3, 6, and 14 days after enrollment. The primary outcome was treatment failure (clinical deterioration) by day 6. Analyses were done per protocol and by intention to treat. This trial is registered, ISRCTN95821329.\n In the per-protocol population, 36 individuals were excluded from the hospitalised group and 37 from the ambulatory group, mainly because of protocol violations or loss to follow-up. There were 87 (8.6%) treatment failures in the hospitalised group and 77 (7.5%) in the ambulatory group (risk difference 1.1%; 95% CI -1.3 to 3.5) by day 6. Five (0.2%) children died within 14 days of enrollment, one in the ambulatory group and four in the hospitalised group. In each case, treatment failure was declared before death and the antibiotic had been changed. None of the deaths were considered to be associated with treatment allocation; there were no serious adverse events reported in the trial.\n Home treatment with high-dose oral amoxicillin is equivalent to currently recommended hospitalisation and parenteral ampicillin for treatment of severe pneumonia without underlying complications, suggesting that WHO recommendations for treatment of severe pneumonia need to be revised.", "Injectable penicillin is the recommended treatment for WHO-defined severe pneumonia (lower chest indrawing). If oral amoxicillin proves equally effective, it could reduce referral, admission, and treatment costs. We aimed to determine whether oral amoxicillin and parenteral penicillin were equivalent in the treatment of severe pneumonia in children aged 3-59 months.\n This multicentre, randomised, open-label equivalency study was undertaken at tertiary-care centres in eight developing countries in Africa, Asia, and South America. Children aged 3-59 months with severe pneumonia were admitted for 48 h and, if symptoms improved, were discharged with a 5-day course of oral amoxicillin. 1702 children were randomly allocated to receive either oral amoxicillin (n=857) or parenteral penicillin (n=845) for 48 h. Follow-up assessments were done at 5 and 14 days after enrollment. Primary outcome was treatment failure (persistence of lower chest indrawing or new danger signs) at 48 h. Analyses were by intention-to-treat and per protocol.\n Treatment failure was 19% in each group (161 patients, pencillin; 167 amoxillin; risk difference -0.4%; 95% CI -4.2 to 3.3) at 48 h. Infancy (age 3-11 months; odds ratio 2.72, 95% CI 1.95 to 3.79), very fast breathing (1.94, 1.42 to 2.65), and hypoxia (1.95, 1.34 to 2.82) at baseline predicted treatment failure by multivariate analysis.\n Injectable penicillin and oral amoxicillin are equivalent for severe pneumonia treatment in controlled settings. Potential benefits of oral treatment include decreases in (1) risk of needle-borne infections; (2) need for referral or admission; (3) administration costs; and (4) costs to the family.", "Since community-acquired pneumonia (CAP) is a common disease with a high morbidity rate, it is important to obtain information concerning its etiology and susceptibility to antibiotics across different geographic areas. This study presents data obtained in 5 Latin American counties in the course of an international clinical trial that evaluated the efficacy and safety of treatment with either moxifloxacin or amoxicillin administered for 10 days to patients suspected of having CAP caused by a pneumococcal infection. Details are given of the pathogens identified, the patterns of sensitivity to antibiotics observed, and the clinical and microbiological results obtained.A total of 84 patients were studied, of whom 70 (83.3%) were evaluated at the end of the trial to determine the efficacy and safety of the treatment received. Gram-positive bacteria were found in samples from 29 patients (80.5%). The pathogen was Streptococcus pneumoniae in 28 of those cases (77.7%). Gram-negative bacteria were found in 7 patients (19.4%), the most common being Haemophilus influenzae in 3 patients (8.3%). The presence of atypical microorganisms was detected in 18 of the 70 patients (25%), mainly Mycobacterium pneumoniae (n=11), and in 6 cases (8.5%) the infection was mixed. Ten strains of S. pneumoniae (35.7%) were shown to be susceptible to penicillin, 2 (7.1%) were highly resistant, and 16 (57.1%) showed moderate resistance. The clinical success rate at the final visit after treatment was 94.1% for moxifloxacin and 91.7% for amoxicillin. The results of this trial demonstrate a high prevalence of S. pneumoniae with reduced susceptibility to penicillin in patients with CAP in Latin America. It also revealed a high incidence of atypical pathogens and mixed infection in 8.6% of patients. This information should be taken into account when establishing protocols for empirical treatment of CAP in Latin America.", "Levofloxacin has established efficacy and safety in the treatment of community-acquired pneumonia (CAP) in adults, and its use as an alternative therapy for children with CAP has been proposed.\n Assess the clinical efficacy and safety of levofloxacin compared with standard of care antibiotic therapy in the treatment of CAP in children aged 6 months to 16 years.\n In an open-label, multicenter, noninferiority trial, children with CAP were randomized 3:1 to receive levofloxacin or comparator antimicrobial therapy (0.5 to <5 years: amoxicillin/clavulanate or ceftriaxone; > or =5 years: clarithromycin or ceftriaxone with clarithromycin or erythromycin lactobinate) for 10 days. The primary outcome was cure rates at the test-of-cure visit (10-17 days after completing treatment) as determined by symptoms, physical examination, and chest radiography.\n Seven hundred and thirty-eight children were enrolled and 539 (405 levofloxacin-treated, 134 comparator-treated) were clinically evaluable at test-of-cure visit. Clinical cure rates were 94.3% (382 of 405) in levofloxacin-treated and 94.0% (126 of 134) in comparator-treated children. Cure rates were also similar for levofloxacin and comparator for each age group (<5 years, 92.2% versus 90.8%; > or =5 years, 96.5% versus 97.1%; respectively) and for children categorized as being at higher risk for severe disease. Mycoplasma pneumoniae was the most frequently identified cause of pneumonia (230 children). Levofloxacin was as well tolerated as comparators, with similar type and incidence of adverse events.\n Levofloxacin was as well tolerated and effective as standard-of-care antibiotics for the treatment of CAP in infants and children.", "A double-blind randomized controlled trial of amoxycillin, co-trimoxazole, and placebo was conducted on 197 children presenting with presumed viral respiratory infections. Routine throat swabs were taken to exclude streptococcal diseases. The three disease categories studied--nasopharyngitis, pharyngotonsillitis, and bronchitis (including laryngotracheobronchitis)--showed a generally similar pattern of resolution irrespective of treatment. Nevertheless, seven out of 66 children receiving placebo were withdrawn from the trial with unremitting symptoms or complications thought to require antimicrobial treatment. Only two of 56 children receiving amoxycillin and none of 75 receiving co-trimoxazole were withdrawn. Three other children receiving amoxycillin and three receiving placebo were seen during the trial but further treatment was not thought to be necessary. Thus the return consultation rate in children receiving placebo therapy was 15% compared with 4% for those receiving antimicrobial treatment. Antimicrobial treatment was associated with less nasal discharge on the eighth day of treatment. Placebo treatment allowed an earlier return to normal activity. There was a high incidence of possible side effects on all regimens including placebo. It is concluded that the benefits of antimicrobial treatment in presumed viral respiratory infections are marginal, and they should not be routinely prescribed for these conditions.", "134 Gambian children under 5 years of age with severe pneumonia (as defined by the World Health Organisation classification of acute respiratory infections) were given either oral co-trimoxazole for 5 days, or a single intramuscular dose of fortified procaine penicillin and 5 days of oral ampicillin. At 2 weeks, there was no significant difference in outcome between the two groups. Co-trimoxazole is much less expensive than ampicillin or procaine penicillin, requires only twice-daily administration, and can be given by health-care staff with little training. The results support the use of co-trimoxazole as the antibiotic of first choice in outpatient management of young children with pneumonia in developing countries.", "Reported are the results of a randomized trial of sulfamethoxazole + trimethoprim versus procaine penicillin for the outpatient treatment of pneumonia in 614 children aged 3 months to 12 years at primary health care clinics in Chitungwiza, a large town near Harare, Zimbabwe. Diagnosis and treatment were carried out by nurses, without medical supervision. The presence of lower respiratory tract infection that required antibiotics was diagnosed on the basis of a recent history of a cough and the presence of a respiratory rate of greater than 50 per minute. Patients were followed up by a research nurse with minimal drop-out losses. Referred children were examined and assessed by a doctor at the Chitungwiza General Hospital. Of the study children, 65 (11%) were referred to hospital, but only 8 (1.3%) had pneumonia that required a change in the treatment (5 in the sulfamethoxazole + trimethoprim group and 3 in the procaine penicillin group). There were no significant differences in outcome between the two treatment groups. One child, who had evidence of infection with human immunodeficiency virus (HIV), died. Sulfamethoxazole + trimethoprim and procaine penicillin were highly and equally effective for the outpatient treatment of children who had been clinically diagnosed to have pneumonia by primary health care workers.", "To determine if intramuscular (IM) penicillin is more effective than oral (PO) amoxicillin in the early outpatient treatment of pediatric patients with presumed bacterial pneumonia.\n Prospective, randomized, evaluator-blinded, clinical trial.\n Pediatric emergency department (ED) of an urban children's hospital.\n ED patients with radiographically confirmed pneumonias managed as outpatients. Patients with chronic illnesses, wheezing, allergy to amoxicillin or penicillin, recent antibiotic therapy, or concurrent diagnosis of another febrile illness were excluded.\n Patients received either a two-day supply of PO amoxicillin (50 mg/kg/day divided tid), or an IM injection of procaine penicillin G (PPG) (50,000 units/kg). They had a complete blood count (CBC), blood culture, and nasopharyngeal swab for viral culture done at initial visit. They returned in 24 to 36 hours for reevaluation.\n The main measures were temperature, respiratory rate, and general appearance score; additional measures were accessory muscle use, pulse oximetry, parental report of activity/oral intake.\n One hundred seventy patients were enrolled. There were no significant differences between the two groups at initial or follow-up visits with respect to temperature, respiratory rate, accessory muscle use, pulse oximetry, or parental reports of activity level and oral intake. Only in the general appearance of children less than two years of age did there appear to be a difference (P = 0.03). When subanalysis excluded patients with positive viral studies (n = 17) or chest x-rays \"reread\" by an attending pediatric radiologist as \"no infiltrate\" (n = 29), this difference disappeared (P = 0.10). Three patients in the PO group, and five in the IM group failed by all three main outcome measures (P = 1.00). Four patients in the PO group, and five in the IM group were hospitalized at the follow-up visit (P = 1.00).\n There does not appear to be a significant difference between PO amoxicillin and IM penicillin in the early outpatient treatment of pediatric patients with presumed bacterial pneumonia.", "To assess the efficacy of three days versus five days of treatment with oral amoxicillin for curing non-severe pneumonia in children.\n Randomised, double blind, placebo controlled multicentre trial.\n Outpatient departments of seven referral hospitals in India.\n 2188 children aged 2-59 months, 1095 given three days of treatment and 1093 given five days.\n Oral amoxicillin 31-54 mg/kg/day in three divided doses.\n Treatment failure: defined as development of chest indrawing, convulsions, drowsiness, or inability to drink at any time; respiratory rate above age specific cut points on day 3 or later; or oxygen saturation by pulse oximetry < 90% on day 3.\n The clinical cure rates with three days and five days of treatment were 89.5% and 89.9%, respectively (absolute difference 0.4 (95% confidence interval--2.1 to 3.0)). Adherence to treatment regimen was 94% and 85% for three day and five day treatments, respectively. Loss to follow up was 5.4% by day 5. There were no deaths, 41 hospitalisations, and 36 minor adverse reactions. There were 225 (10.3%) clinical failures and 106 (5.3%) relapses, and rates were similar in both treatments. At enrollment, 513 (23.4%) children tested positive for respiratory syncytial virus, and Streptococcus pneumoniae and Haemophilus influenzae were isolated from the nasopharynx in 878 (40.4%) and 496 (22.8%) children, respectively. Clinical failure was associated with isolation of respiratory syncytial virus (adjusted odds ratio 1.95 (95% confidence interval 1.0 to 3.8)), excess respiratory rate of > 10 breaths/minute (2.89 (1.83 to 4.55)), and non-adherence with treatment at day 5 (11.57 (7.4 to 18.0)).\n Treatment with oral amoxicillin for three days was as effective as for five days in children with non-severe pneumonia.", "To assess the effectiveness of ampicillin and a combination of benzyl penicillin and chloramphenicol in the treatment of pneumonias.\n Randomized controlled trial.\n Tertiary care hospital.\n Patients 5 months to 4 years old with pneumonias of < 2 weeks duration. Exclusion criteria included acute bronchiolitis, allergy to penicillin, postmeasles pneumonia or prior administration of trial antibiotics in full dose for more than 2 days.\n Patients were randomized to receive either ampicillin (100 mg/kg/day) or combination of benzyl penicillin (100,000 units/kg/day) and chloramphenicol (100 mg/kg/day). The outcome measure was cure rate.\n There were 52 and 49 patients in the ampicillin and the combination groups, respectively. There was no significant difference in the baseline characteristics between groups except, nasal flare and cyanosis which were less in benzyl penicillin plus chloramphenicol group. There was also no difference either in the primary outcome, cure rate or secondary outcomes (days for cure, duration of tachypnea, fever and grunt) in the two.\n Considering the potential toxicity of chloramphenicol and the number of injections and doses to be given for the combination, ampicillin as a single drug could be preferred for the treatment of pneumonias, in this part of the country.", "Levofloxacin, an antibiotic from the quinolone family, which is used with success in the ambulatory treatment of patients with community-acquired pneumonia, has been recently introduced to the pharmaceutical market. The purpose of this study was to compare the effectiveness and tolerance of oral (v.o.) levofloxacin (LVF) versus intravenous (i.v.) amoxicillin/clavulanate (AMX/CL) and ceftriaxone (CTX) in the treatment of the community-acquired pneumonia that require hospitalization (CAPH).\n In this prospective and randomized study 84 patients were included, 28 per group, from both sex with CAPH. The patients were assigned randomly to receive one of the next treatments: AMX/CL, 1.02 g i.v. every 8 h, CTX, 1 g i.v. every 12 h or LVF, 500 mg v.o. every 24 h. At the beginning clinical, biochemical and radiological characteristics were recorded from each case and at the 72 h the effect of treatment was evaluated using the evolution of the thermal curve and radiological images. The quantitative variables were analyzed with ANOVA, the qualitatives parameters with 2 test and Yates correction. The level of signification was = 0.05.\n Age, sex, clinical presentation, biochemical measurements and radiological images in the 3 groups were similar and no adverse effects were recorded in any of them. Number of patients with favorable outcome in the groups AMX/CL, CTX and LVF was 25 (89%), 25 (89%) and 26 (93%); p = 0,870.\n Levofloxacin can be a simple, effective and safe therapeutic option for patients with CAPH.", "Fear of infection in neonatal intensive care units (NICUs) often leads to early use of empiric broad-spectrum antibiotics, a strategy that selects for resistant bacteria. We investigated whether the emergence of resistant strains could be halted by modifying the empiric antibiotic regimens to remove the selective pressure that favours resistant bacteria.\n Two identical NICUs were assigned to different empiric antibiotic regimens. On unit A, penicillin G and tobramycin were used for early-onset septicaemia, flucloxacillin and tobramycin were used for late-onset septicaemia, and no broad-spectrum beta-lactam antibiotics, such as amoxicillin and cefotaxime were used. In unit B, intravenous amoxicillin with cefotaxime was the empiric therapy. After 6 months of the study the units exchanged regimens. Rectal and respiratory cultures were taken on a weekly basis.\n There were 436 admissions, divided equally between the two regimens (218 in each). Three neonates treated with the penicillin-tobramycin regimen became colonised with bacilli resistant to the empirical therapy used versus 41 neonates on the amoxicillin-cefotaxime regimen (p<.0001). The relative risk for colonisation with strains resistant to the empirical therapy per 1000 patient days at risk was 18 times higher for the amoxicillin-cefotaxime regimen compared with the penicillin-tobramycin regimen (95% CI 5.6-58.0). Enterobacter cloacae was the predominant bacillus in neonates on the amoxicillin-cefotaxime regimen, whereas Escherichia coli predominated in neonates on the penicillin-tobramycin regimen. These colonisation patterns were also seen when the units exchanged regimens.\n Policies regarding the empiric use of antibiotics do matter in the control of antimicrobial resistance. A regimen avoiding amoxicillin and cefotaxime restricts the resistance problem.", "In a prospective randomised controlled trial, amoxycillin plus clavulanic acid was compared to a combination of cefotaxime and metronidazole as prophylactic antibiotics in 164 patients who underwent elective colorectal resectional surgery. Wound infection occurred in 15 patients (9.1%) and deep surgical infection in 4 (2.4%). Seven cases of wound infection and 2 cases of deep infection occurred in the amoxycillin plus clavulanic acid arm, while 8 cases of wound infection and 2 cases of deep infection occurred in the cefotaxime plus metronidazole arm. Eighty-eight percent of infections occurred in patients who had low anterior resection or abdominoperineal resection of the rectum. Both the amoxycillin plus clavulanic acid and the combination of cefotaxime and metronidazole offer the same degree of protection against post-operative infection. The use of amoxycillin plus clavulanic acid as antibiotic prophylaxis is recommended because of its easier use and cheaper cost.", "748 children with severe pneumonia in three hospitals in Papua New Guinea were randomised to receive intramuscular injections of either chloramphenicol alone or chloramphenicol plus penicillin. Sequential analysis showed no difference between the two treatments. 48 (13%) of the 377 children in the chloramphenicol alone group died, and 3 (0.8%) were changed to different treatment. 62 (17%) of the 371 children in the chloramphenicol-plus-penicillin group died, and 6 (1.6%) were changed to different treatment. The difference in failure rates (death or withdrawal for change of treatment) was 4.8% +/- 5.2% (+/- 95% confidence limits). In children with severe pneumonia, treatment with chloramphenicol alone is as effective as treatment with chloramphenicol plus penicillin.", "To compare the clinical response to amoxicillin, cefuroxime and clarithromycin in the treatment of community-acquired pneumonia in children and to see the cost effectiveness of each treatment.\n Randomized clinical control trial.\n Department of Pediatrics, Khyber teaching hospital, Peshawar, from October 2001 to February 2002.\n Patients between 3 to 72 months of age, admitted in the hospital with community acquired pneumonia, were randomly divided into three groups,1,2,3. They were started on amoxicillin, cefuroxime and clarithromycin respectively. The patients were assessed daily. If there was no clinical improvement at 48 hours the antibiotic was changed. ANOVA statistical test was applied to see the clinical response to the treatment in the three groups. Cost effectiveness of the treatment was compared.\n There was no statistical difference in the clinical response at 48 hours of initiating treatment and at discharge (p > 0.01 each). The mean hospital stay in group 1 and 2 was 3.3 days and group 3 was 3.2 days respectively (p > 0.01). Ninety-seven percent patients in group 1 and 3, and 95% patients in group 2 showed clinical improvement. The cost of treatment of community acquired pneumonia for 8 days was Rs 496/-, 730/-, 1018/- for amoxicillin, clarithromycin and cefuroxime respectively.\n Amoxicillin was found the most cost effective followed by clarithromycin and cefuroxime respectively in the treatment of non-severe and severe community-acquired pneumonia.", "High dose amoxicillin is recommended for the initial treatment of children with acute otitis media (AOM), particularly patients at risk for having drug-resistant Streptococcus pneumoniae. Single dose azithromycin (30 mg/kg) is considered an alternative agent for the treatment of AOM.\n To compare the clinical efficacy and safety of single dose azithromycin with that of high dose amoxicillin among children with uncomplicated AOM.\n This was a double blind, double dummy, multinational, clinical trial in which children (6-30 months of age) with AOM were randomized to treatment with single dose azithromycin (30 mg/kg) or high dose amoxicillin (90 mg/kg/d, in 2 divided doses) for 10 days. Tympanocentesis was performed at baseline and clinical responses were assessed at days 12-14 (end of therapy) and at days 25-28 (end of study).\n The study enrolled 313 patients, and 83% of the patients were < or =2 years of age. A total of 158 patients in the azithromycin group and 154 in the amoxicillin group were considered clinical modified intent-to-treat patients. A middle ear pathogen was detected for 212 patients (68%). Haemophilus influenzae was the most common pathogen (isolated for 96 patients), followed by S. pneumoniae (92 patients), Moraxella catarrhalis (23 patients) and Streptococcus pyogenes (23 patients). beta-Lactamase production was observed for 17% of H. influenzae isolates and 100% of M. catarrhalis isolates. Thirty-five (38%) S. pneumoniae isolates were penicillin-nonsusceptible and 24 (26%) isolates were macrolide-resistant. At the end of therapy, clinical success rates for azithromycin and amoxicillin were comparable for all patients (84 and 84%, respectively) and for children < or =2 years of age (82 and 82%, respectively). At the end of therapy and end of study, clinical efficacies among all microbiologic modified intent-to-treat evaluable subjects were comparable for patients treated with azithromycin (80%) and patients treated with amoxicillin (83%). The rates of treatment-related adverse events for azithromycin and amoxicillin were 20% and 29%, respectively (P = 0.064). Diarrhea was more common in the amoxicillin group than in the azithromycin group (17.5 and 8.2%, respectively) (P = 0.017). Compliance, defined as completion of > or =80% of the study medication, was higher in the azithromycin group (100%) than in the amoxicillin group (90%) (P = 0.001).\n In this study, single dose azithromycin was as effective as high dose amoxicillin for the treatment of children with AOM, whereas rates of adverse events were lower and compliance improved with the simplified single dose regimen." ]	For treatment of patients with CAP in ambulatory settings, amoxycillin is an alternative to co-trimoxazole. With limited data on other antibiotics, co-amoxyclavulanic acid and cefpodoxime may be alternative second-line drugs. Children with severe pneumonia without hypoxaemia can be treated with oral amoxycillin in an ambulatory setting. For children hospitalised with severe and very severe CAP, penicillin/ampicillin plus gentamycin is superior to chloramphenicol. The other alternative drugs for such patients are co-amoxyclavulanic acid and cefuroxime. Until more studies are available, these can be used as second-line therapies. There is a need for more studies with radiographically confirmed pneumonia in larger patient populations and similar methodologies to compare newer antibiotics. Recommendations in this review are applicable to countries with high case fatalities due to pneumonia in children without underlying morbidities and where point of care tests for identification of aetiological agents for pneumonia are not available.
CD003176	[ "11157692", "17710485", "17485449", "16625008", "17426195" ]	[ "Intravenous immunoglobulin in acute rheumatic fever: a randomized controlled trial.", "Efficacy of corticosteroids in the treatment of community-acquired pneumonia requiring hospitalization.", "Oral versus high-dose pulse corticosteroids for problematic infantile hemangiomas: a randomized, controlled trial.", "Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome.", "Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial." ]	[ "Acute rheumatic fever (ARF) remains the leading cause of acquired heart disease in children worldwide. No therapeutic agent has been shown to alter the clinical outcome of the acute illness. Immunological mechanisms appear to be involved in the pathogenesis of ARF. Intravenous immunoglobulin (IVIG), a proven immunomodulator, may benefit cardiac conditions of an autoimmune nature. We investigated whether IVIG modified the natural history of ARF by reducing the extent and severity of carditis.\n This prospective, double-blind, randomized, placebo-controlled trial evaluated IVIG in patients with a first episode of rheumatic fever, stratifying patients by the presence and severity of carditis before randomization. Patients were randomly allocated to receive 1 g/kg IVIG on days 1 and 2 and 0.4 g/kg on days 14 and 28, or they received a placebo infusion. Clinical, laboratory, and echocardiographic evaluation was performed at 0, 2, 4, 6, 26, and 52 weeks. Fifty-nine patients were treated, of whom 39 had carditis (including 4 subclinical) and/or migratory polyarthritis (n=39). There was no difference between groups in the rate of normalization of the erythrocyte sedimentation rate or acute-phase proteins at the 6-week follow-up. On echocardiography, 59% in the IVIG group and 69% in the placebo group had carditis at baseline. There was no significant difference in the cardiac outcome, including the proportion of valves involved, or in the severity of valvar regurgitation at 1 year. At 1 year, 41% of the IVIG and 50% of the placebo group had carditis.\n IVIG did not alter the natural history of ARF, with no detectable difference in the clinical, laboratory, or echocardiographic parameters of the disease process during the subsequent 12 months.", "Recent studies suggested that administration of corticosteroids may improve clinical outcomes in patients with severe pneumonia.\n The aim of this study was to assess the effectiveness of corticosteroids as an adjunctive therapy in community-acquired pneumonia (CAP) requiring hospitalization.\n An open label, prospective, randomized control study was conducted from September 2003 to February 2004 in a community general hospital in Japan.\n Thirty-one adult CAP patients who required hospitalization were enrolled.\n Fifteen patients received 40 mg of prednisolone intravenously for 3 days (steroid group). Sixteen patients did not receive prednisolone (control group). Both groups were also evaluated for their adrenal function. The primary endpoint was length of hospital stay. Secondary endpoints were duration of intravenous (IV) antibiotics and time required to stabilize vital signs. Both groups demonstrated similar baseline characteristics and length of hospital stay, and yet a shorter duration of IV antibiotics was observed in the steroid group (p < 0.05). In addition, vital signs were stabilized earlier in the steroid group (p < 0.05). These differences were more prominent in the moderate-severe subgroup but not as significant in the mild-moderate subgroup. The prevalence of relative adrenal insufficiency (RAI) in both groups was high (43%), yet there was no difference in baseline characteristics between patients, with or without RAI. In multiple regression models, RAI seemed to have no influence on clinical courses.\n In moderate-severe CAP, administration of corticosteroids promotes resolution of clinical symptoms and reduces the duration of intravenous antibiotic therapy.", "Oral systemic corticosteroids are the mainstay of treatment for problematic hemangiomas; however, current information is based on anecdotal experience and retrospective studies. We aimed to determine whether systemic steroids are efficacious in proliferating hemangioma and to compare the efficacy and safety of 2 corticosteroid treatment modalities.\n Twenty patients with problematic hemangiomas of infancy were randomly assigned to either daily oral prednisolone or monthly intravenous pulses of methylprednisolone. Their clinical outcomes (improvement using a visual analog score) and adverse events were compared at 3 months from baseline and 1 year of age. Data on possible surrogate markers of angiogenesis were available for the first 3 months.\n At 3 months, orally treated patients had a median visual analog score of 70 compared with 12 in the intravenous group. This response pattern was similar at the patients' first birthday: 50.0 vs -1.5. Additional treatment beyond 3 months was needed for 65% of the patients (7 in the intravenous and 6 in the oral group). Six of 8 patients with impaired vision at enrollment had an improved function at 1 year (4 patients in the intravenous group and 3 patients in the oral group). Of the 4 surrogate markers of angiogenesis measured (plasma basic fibroblast growth factor, vascular endothelial growth factor, vascular cellular adhesion molecule 1, endoglin, and urine basic fibroblast growth factor), the only 2 that decreased over time were vascular cellular adhesion molecule 1 and endoglin. Patients in the oral group had a higher rate of adverse effects, such as hypertension (18.6% vs 13.1%), abnormal cortisol (78% vs 60%), and growth retardation.\n Systemic corticosteroids are efficacious in stopping the proliferation of hemangiomas. The oral corticosteroids offered more clinical and biological benefit than the pulse steroids with higher risk of adverse effects.", "Persistent acute respiratory distress syndrome (ARDS) is characterized by excessive fibroproliferation, ongoing inflammation, prolonged mechanical ventilation, and a substantial risk of death. Because previous reports suggested that corticosteroids may improve survival, we performed a multicenter, randomized controlled trial of corticosteroids in patients with persistent ARDS.\n We randomly assigned 180 patients with ARDS of at least seven days' duration to receive either methylprednisolone or placebo in a double-blind fashion. The primary end point was mortality at 60 days. Secondary end points included the number of ventilator-free days and organ-failure-free days, biochemical markers of inflammation and fibroproliferation, and infectious complications.\n At 60 days, the hospital mortality rate was 28.6 percent in the placebo group (95 percent confidence interval, 20.3 to 38.6 percent) and 29.2 percent in the methylprednisolone group (95 percent confidence interval, 20.8 to 39.4 percent; P=1.0); at 180 days, the rates were 31.9 percent (95 percent confidence interval, 23.2 to 42.0 percent) and 31.5 percent (95 percent confidence interval, 22.8 to 41.7 percent; P=1.0), respectively. Methylprednisolone was associated with significantly increased 60- and 180-day mortality rates among patients enrolled at least 14 days after the onset of ARDS. Methylprednisolone increased the number of ventilator-free and shock-free days during the first 28 days in association with an improvement in oxygenation, respiratory-system compliance, and blood pressure with fewer days of vasopressor therapy. As compared with placebo, methylprednisolone did not increase the rate of infectious complications but was associated with a higher rate of neuromuscular weakness.\n These results do not support the routine use of methylprednisolone for persistent ARDS despite the improvement in cardiopulmonary physiology. In addition, starting methylprednisolone therapy more than two weeks after the onset of ARDS may increase the risk of death. (ClinicalTrials.gov number, NCT00295269.).\n Copyright 2006 Massachusetts Medical Society.", "To determine the effects of low-dose prolonged methylprednisolone infusion on lung function in patients with early severe ARDS.\n Randomized, double-blind, placebo-controlled trial.\n ICUs of five hospitals in Memphis.\n Ninety-one patients with severe early ARDS (</= 72 h), 66% with sepsis.\n Patients were randomized (2:1 fashion) to methylprednisolone infusion (1 mg/kg/d) vs placebo. The duration of treatment was up to 28 days. Infection surveillance and avoidance of paralysis were integral components of the protocol.\n The predefined primary end point was a 1-point reduction in lung injury score (LIS) or successful extubation by day 7.\n In intention-to-treat analysis, the response of the two groups (63 treated and 28 control) clearly diverged by day 7, with twice the proportion of treated patients achieving a 1-point reduction in LIS (69.8% vs 35.7%; p = 0.002) and breathing without assistance (53.9% vs 25.0%; p = 0.01). Treated patients had significant reduction in C-reactive protein levels, and by day 7 had lower LIS and multiple organ dysfunction syndrome scores. Treatment was associated with a reduction in the duration of mechanical ventilation (p = 0.002), ICU stay (p = 0.007), and ICU mortality (20.6% vs 42.9%; p = 0.03). Treated patients had a lower rate of infections (p = 0.0002), and infection surveillance identified 56% of nosocomial infections in patients without fever.\n Methylprednisolone-induced down-regulation of systemic inflammation was associated with significant improvement in pulmonary and extrapulmonary organ dysfunction and reduction in duration of mechanical ventilation and ICU length of stay." ]	There is little evidence of benefit from using corticosteroids or intravenous immunoglobulins to reduce the risk of heart valve lesions in patients with acute rheumatic fever. The antiquity of most of the trials restricted adequate statistical analysis of the data and acceptable assessment of clinical outcomes by current standards. Additionally there was substantial risk of bias, so results should be viewed with caution. New randomised controlled trials in patients with acute rheumatic fever to assess the effects of corticosteroids such as oral prednisone and intravenous methylprednisolone, and other new anti-inflammatory agents are warranted. Advances in echocardiography will allow for more objective and precise assessments of cardiac outcomes.
CD003030	[ "16708003", "16332553", "3985516", "12757433", "3218878", "8676185", "8067649", "3374415", "8320576", "10723618", "1861939", "6859657", "6406886", "3977198", "11942445", "7603933", "16707508", "6208312", "12106617", "18237352", "9625213", "8635032", "16740859", "8034151", "14729297", "10147031", "15858816", "2867269", "8667091", "10480825", "7406934", "12915605", "10422481", "12817353", "7974314", "10610626", "7373255", "12781926", "18777429", "8936577", "1571645", "8874688", "16882375", "19395710", "20841574", "3941533", "10302610", "12356708", "8917146", "11903763", "6153057", "3980239", "16102151", "18216062", "15249521", "2373065", "18166837", "15904552", "3381783", "7837822", "10888694", "3339482", "14521638", "9120651", "18823177", "10508816", "16186262", "3698783", "9565408", "12603357", "15861266", "430774", "7677554", "8549258", "21350242" ]	[ "Cluster randomized controlled trial of the effectiveness of audit and feedback and educational outreach on improving nursing practice and patient outcomes.", "Promoting a biopsychosocial orientation in family practice: effect of two teaching programs on the knowledge and attitudes of practising primary care physicians.", "The effectiveness of continuing medical education in changing the behavior of physicians caring for patients with acute myocardial infarction. A controlled randomized trial.", "Educational workshop improved information-seeking skills, knowledge, attitudes and the search outcome of hospital clinicians: a randomised controlled trial.", "A randomized controlled trial assessing the impact of problem-based versus didactic teaching methods in CME.", "Improving drug use through continuing education: a randomized controlled trial in Zambia.", "Improving office-based physician's prevention practices for sexually transmitted diseases.", "The effects of continuing medical education on family doctor performance in office practice: a randomized control study.", "The effects of two continuing medical education programs on communication skills of practicing primary care physicians.", "Empowering older patients to communicate more effectively in the medical encounter.", "Increasing patient knowledge, satisfaction, and involvement: randomized trial of a communication intervention.", "Continuing education in pulmonary disease for primary-care physicians.", "Improving drug-therapy decisions through educational outreach. A randomized controlled trial of academically based \"detailing\".", "Expanding patient involvement in care. Effects on patient outcomes.", "A randomised controlled trial of the effect of educational outreach by community pharmacists on prescribing in UK general practice.", "Evaluation of a patient education leaflet designed to improve communication in medical consultations.", "Effect of patient completed agenda forms and doctors' education about the agenda on the outcome of consultations: randomised controlled trial.", "The efficacy of personalized audiovisual patient-education materials.", "Effect of patient education on self-management skills and health status in patients with asthma: a randomized trial.", "Strategies for improving the quality of health care in maternal and child health in low- and middle-income countries: an overview of systematic reviews.", "Improving communication skills--a randomized controlled behaviorally oriented intervention study for residents in internal medicine.", "Increasing patient involvement in choosing treatment for early breast cancer.", "Impact of physician asthma care education on patient outcomes.", "Educating asthmatic patients in primary care: a pilot study of small group education.", "Promoting patient participation in consultations: a randomised controlled trial to evaluate the effectiveness of three patient-focused interventions.", "The economics of an intensive education programme for asthmatic patients: a prospective controlled trial.", "Physicians' communication with a cancer patient and a relative: a randomized study assessing the efficacy of consolidation workshops.", "Controlled evaluation of the effects of patient education on asthma morbidity in general practice.", "Effects of a physician communication intervention on patient care outcomes.", "Improving the health behaviours of elderly people: randomised controlled trial of a general practice education programme.", "Evaluation of a continuing education program in rheumatoid arthritis.", "How to optimize physicians' communication skills in cancer care: results of a randomized study assessing the usefulness of posttraining consolidation workshops.", "Patient and relative education in community psychiatry: a randomized controlled trial regarding its effectiveness.", "Modifying dyspepsia management in primary care: a cluster randomised controlled trial of educational outreach compared with passive guideline dissemination.", "Prospective controlled evaluation of the effect of a community based asthma education centre in a multiracial working class neighbourhood.", "Effect of clinician communication skills training on patient satisfaction. A randomized, controlled trial.", "Effectiveness of patient education and psychosocial counseling in promoting compliance and control among hypertensive patients.", "Increasing patient participation in reproductive health consultations: an evaluation of \"Smart Patient\" coaching in Indonesia.", "Cross-cultural medical education: can patient-centered cultural competency training be effective in non-Western countries?", "Does a 3-day workshop for family medicine trainees improve preventive care? A randomized control trial.", "Randomised trial of three approaches for marketing smoking cessation programmes to Australian general practitioners.", "Effect of training and a structured office practice on physician-delivered nutrition counseling: the Worcester-Area Trial for Counseling in Hyperlipidemia (WATCH).", "Effective improvement of doctor-patient communication: a randomised controlled trial.", "A hospital-randomized controlled trial of a formal quality improvement educational program in rural and small community Texas hospitals: one year results.", "Game-based versus traditional case-based learning: comparing effectiveness in stroke continuing medical education.", "Does a mailed continuing education program improve physician performance? Results of a randomized trial in antihypertensive care.", "Encouraging patient question-asking: a clinical trial.", "Educational strategies to promote evidence-based community pharmacy practice: a cluster randomized controlled trial (RCT).", "Patient-initiated prevention discussions. Two interventions to stimulate patients to initiate prevention discussions.", "Resident utilization of information technology.", "Improving hypertension control: impact of computer feedback and physician education.", "Evaluation of family health education to build social support for long-term control of high blood pressure.", "The impact of a nurse-led support and education programme for spouses of stroke patients: a randomized controlled trial.", "Standard versus patient-centred asthma education in the emergency department: a randomised study.", "Patient-based outcome results from a cluster randomized trial of shared decision making skill development and use of risk communication aids in general practice.", "Patient-oriented interventions to improve communication in a medical office visit.", "An educational video to increase clinical trials enrollment among lung cancer patients.", "The effect of educational intervention on intercultural communication: results of a randomised controlled trial.", "Improving pediatricians' compliance-enhancing practices. A randomized trial.", "The effect of an education and feedback intervention on group-model and network-model health maintenance organization physician prescribing behavior.", "An evaluation of an innovative multimedia educational software program for asthma management: report of a randomized, controlled trial.", "The Diabetes Education Study: a controlled trial of the effects of intensive instruction of internal medicine residents on the management of diabetes mellitus.", "Randomized controlled trial of education and feedback for implementation of guidelines for acute low back pain.", "Strategies to promote the use of advance directives in a residency outpatient practice.", "Physician and patient communication training in primary care: effects on participation and satisfaction.", "Evaluating an educational intervention to improve the treatment of asthma in four European countries. Drug Education Project Group.", "An endocrinologist-supported intervention aimed at providers improves diabetes management in a primary care site: improving primary care of African Americans with diabetes (IPCAAD) 7.", "A randomized study of the effects of a home diabetes education program.", "Intervention to improve physician documentation and knowledge of child sexual abuse: a randomized, controlled trial.", "Multimedia versus written information for nocturnal enuresis education: a cluster randomized controlled trial.", "Effects of formal education for patients with inflammatory bowel disease: a randomized controlled trial.", "Education for self-treatment by adult asthmatics.", "Improving physicians' interviewing skills and reducing patients' emotional distress. A randomized clinical trial.", "The impact of an educational program on improving diabetes knowledge and changing behaviors of nurses in long-term care facilities.", "A randomized trial of effects of health risk appraisal combined with group sessions or home visits on preventive behaviors in older adults." ]	[ "Current understanding of implementation methods is limited, and research has focused on changing doctors' behaviors.\n Our aim was to evaluate the impact of audit and feedback and educational outreach in improving nursing practice and patient outcomes.\n Using a factorial design, cluster randomized controlled trial, we evaluated 194 community nurses in 157 family practices and 1078 patients with diagnosis of urinary incontinence (UI) for nurses compliance with evidence-linked review criteria for the assessment and management of UI and impact on psychologic and social well-being and symptoms. In the outreach arms, nurses' self-reported barriers informed development of tailored strategies.\n In comparison with educational materials alone, the implementation methods tested did not improve care at 6 months follow-up. Moderate rates of improvement (10-17% of patients) in performance for the assessment of UI and greater rates of improvement (20-30% of patients) for the management of care were found but effects were similar across arms. Improvement in patient outcomes was more consistently positive for educational outreach than for audit and feedback but differences were not significant. Adjustment for caseload size, severity or duration of UI and patients' age did not alter results.\n Printed educational materials alone may be as effective as audit and feedback and educational outreach in improving nurses' performance and outcomes of care for people with UI. Greater understanding of the underlying processes in improving performance within multidisciplinary teams through further, theory-driven studies with \"no intervention\" control groups and longer follow-up are needed.", "The bio-psychosocial (BPS) approach to patient care has gained acceptance in medical education. However, reported teaching programs rarely describe the efficacy of alternative approaches to continuing medical education aimed at promoting a BPS approach. The objective was to describe and evaluate the effect of two teaching programs on learners' BPS knowledge, management intentions, patient-centered attitudes, professional self-esteem, burnout, work related strain and mental workload. The learners were Israeli general practitioners. The first (\"didactic\") program consisted of problem-based reading assignments, lectures and discussions. The second (\"interactive\") program consisted of reading assignments, lectures and discussions, in addition to role-playing exercises, Balint groups and one-to-one counseling by a facilitator. One month before and six months after the teaching interventions, we used structured questionnaires to test for knowledge, management intentions (responses to questions, such as \"what would you tell a patient with ...\") and attitudes. Both programs led to measurable improvement in knowledge, intentions, patient-centered attitudes and self-esteem. The interactive teaching approach improved significantly more the learners' professional self-esteem and intentions than the didactic approach. Self-reported burnout significantly increased after the program. It is concluded that teaching intervention enhanced a BPS orientation and led to changes in knowledge, intentions, self-esteem and attitudes. An interactive method of instruction was more effective in achieving some of these objectives than a didactic one. The observed increase in burnout was unexpected and requires further study and confirmation.", "A randomized controlled trial was done to assess the ability of continuing medical education to change physicians' knowledge and behavior in the care of patients with acute myocardial infarction. Patient care practices on eight objectives were audited 6 months before and after physicians completed a 2-hour educational program. Sixty-three physicians from eight randomly selected communities constituted the experimental group and 40 physicians from four similar communities served as controls. The average score for desired care practices over all objectives increased from 48.5% to 60% (p less than 0.001). Three objectives showed significantly greater gains for physicians in the experimental group. The generalizability of these effects was also studied in two additional educational contexts: a multitopic and a unitopic university-based continuing medical education program. Similar significant changes in behavior resulted in both contexts. Significant overall increases in knowledge occurred and persisted for all groups. Continuing medical education can effect changes in physicians' knowledge and care practices that can persist for at least 6 months.", "A double-blind randomised controlled trial was conducted on a group of Hong Kong hospital clinicians. The objective was to test if a three-hour educational workshop (with supervised hands-on practice) is more effective (than no training) to improve clinical question formulation, information-seeking skills, knowledge, attitudes, and search outcomes. The design was a post-test-only control group; recruitment by stratified randomization (by profession), blocked at 800. End-user training was more effective than no training in improving clinical question formulation, in raising awareness, knowledge, confidence and use of databases, but had made no impact on preference for secondary databases. It changed the attitude of clinicians to become more positive towards the use of electronic information services (EIS). Participants had higher search performance and outcomes (satisfaction with information obtained (NNT = 3), EIS satisfaction (NNT = 3) and success in problem solving (NNT = 4)). The workshop improved knowledge and skills in evidence-based searching, but this effect gradually eroded with time. Search logs confirmed that follow-up is required if effects are to be sustained. Longer effects on search behaviours appear to be positive. A randomised controlled trial is valuable in identifying cause-and-effect relations and to quantify the magnitude of the effects for management decision-making.", "A Continuing Medical Education short course was designed to examine the effect of presenting topics in three learning formats - traditional lectures, large-group, case discussions or small-group, problem-solving sessions, on knowledge and performance of family physicians. The physicians in the small group session rated the CME short course higher and performed better on one aspect of patient management than the lecture or large group physicians but there were no other differences between groups on knowledge or physician performance.", "The objective of this study was to evaluate the impact of three continuing education seminars (within a period of 4 months) on the quality of patient management and rational drug use. The study was designed as a randomized controlled trial. Prescribers in 16 general health centers were allocated to an intervention (eight health centers) or a control (eight health centers) group. A total of 5,685 patient cards was analyzed for quality of case management and rational drug use. In the intervention health centers the average number of drugs per patient decreased from 2.3 to 1.9 (p = 0.005) and the proportion of patients managed with nonpharmacological treatment increased from 1 to 13.2%. Recorded history taking, examination, and diagnosis improved in the intervention health centers. More drugs were correctly chosen in the intervention health centers compared to control health centers (p = 0.03). The proportion of patients prescribed antibiotics decreased and the proportion of patients adequately managed increased in the intervention health centers. Our conclusion is that continuing education in the form of repeated seminars is effective in influencing prescribers and in promoting rational drug use in primary care.", "To determine whether office-based interventions increase primary care physicians' risk assessment of and counseling practices for patients regarding sexually transmitted diseases and the human immunodeficiency virus (HIV).\n Randomized controlled clinical trial.\n Washington, D.C., Metropolitan Statistical Area.\n Office-based primary care physicians (family or general practice, internal medicine, and obstetrics-gynecology).\n Mailed educational materials alone or coupled with a simulated patient instructor office visit.\n Self-reported and observed frequency of assessing and counseling patients regarding their risk factors for sexually transmitted diseases and HIV infection. Participants were interviewed by telephone before and after the intervention (n = 757). A subset of participants (n = 194) was also observed after the intervention by simulated patient evaluators in blinded office visits.\n 89% of physicians who received both educational materials and a simulated patient instructor visit reported that they reviewed the educational materials compared with 53% of those who only received the educational materials (P < or = 0.001). Physicians in the combined intervention group had higher self-reported and observed rates for several risk assessment questions and counseling recommendations than did physicians in the control group or the group that only received educational materials. Seventy-three percent of physicians of the combined intervention group reported an increase in counseling patients about reducing risky sexual behavior compared with 53% of the group receiving only educational materials and 42% of the control group (P < or = 0.001).\n Mailed educational materials combined with an office visit by a simulated patient instructor for role-play and feedback on clinical performance increased the frequency of office-based physicians' risk assessment and risk reduction counseling of patients for sexually transmitted diseases and HIV infection.", "A randomized controlled study was conducted to determine if specifically designed continuing medical education in the fields of cardiovascular and cancer medicine could change doctor office behaviour significantly. Thirty-one volunteer family doctors from 25 offices participated. Six (three cardiovascular and three cancer) learning objectives were defined. Two educational formats were selected as the independent variables: (1) group interaction opportunities (face-to-face and teleconference); and (2) concisely written newsletters. Chart measures of doctor performance prior to and 6 and 12 months following education served as the dependent variables. The family doctors receiving education were found to perform the recommended behaviours significantly more than those who did not receive the education (P less than 0.05) at 6 months post-education. This difference was maintained at the 12-month post-educational period for one of the educational programmes offered. A carefully planned programme of continuing medical education will result in favourable changes in the office practice of volunteer doctors. These changes can persist for as long as 12 months. Adherence to several essential learning principles is required.", "To evaluate and compare the effects of two types of continuing medical education (CME) programs on the communication skills of practicing primary care physicians.\n Fifty-three community-based general internists and family practitioners practicing in the Portland, Oregon, metropolitan area and 473 of their patients.\n For the short program (a 4 1/2-hour workshop), 31 physicians were randomized to either the intervention or the control group. In the long program (a 2 1/2-day course), 20 physicians participated with no randomization. A research assistant visited all physicians' offices both one month before and one month after the CME program and audiotaped five sequential visits each time. Data were based on analysis of the content and the affect of the interviews, using the Roter Interactional Analysis Scheme.\n Based on both t-test analysis and analysis of covariance, no effect on communication was evident from the short program. The physicians enrolled in the long program asked more open-ended questions, more frequently asked patients' opinions, and gave more biomedical information than did the physicians in the short program. Patients of the physicians who attended the long program tended to disclose more biomedical and psychosocial information to their physicians. In addition, there was a decrease in negative affect for both patient and physician, and patients tended to demonstrate fewer signs of outward distress during the visit.\n This study demonstrates some potentially important changes in physicians' and patients' communication after a 2 1/2-day CME program. The changes demonstrated in both content and affect may have important influences on both biologic outcome and physician and patient satisfaction.", "Active involvement of patients in medical encounters has been associated with several desirable outcomes, including greater satisfaction, increased adherence to treatment, and positive treatment outcomes. Older patients, particularly the very old and less well educated, are more likely to place physicians in a dominant role and themselves in a submissive role. Intervention trials to increase patient involvement have shown positive results. Activation interventions with older patients to increase a sense of control and self-efficacy are promising. Most of the attention to improving doctor-patient interaction has been directed toward physicians. The results of these few intervention trials support increased attention to patient behaviors.", "A brief educational intervention to promote effective communication between physicians, children, and parents during pediatric office visits was designed and tested. A randomized clinical trial involving 141 children (5- to 15-year-olds) tested the effectiveness of the intervention to improve the process and outcome of medical care. The intervention was contained in three brief videotapes (one each for parents, physicians, and patients) and in accompanying written materials. Materials were designed to build skills and motivation for increased child competence and participation during pediatric medical visits. Control subjects saw health education videotapes and received materials comparable in length with those of experimental subjects. Postintervention medical visit process was analyzed using videotapes of visits. Visit outcomes, assessed with standardized instruments and interviews, included children's rapport with physicians, children's anxiety, children's preference for an active health role, children's recall of information, parents' satisfaction with the medical visit, and physician satisfaction. Results indicated that physicians in the intervention group, compared with their counterparts in the control group, more often included children in discussions of medical recommendations (50% vs 29%, t = 2.39, P less than .05); that children in the intervention group, compared with control children, recalled more medication recommendations (77% vs 47%, P less than .01) and reported greater satisfaction and preference for an active health role; and that the intervention and control groups did not differ in parent satisfaction, physician satisfaction, or child anxiety. The results suggest that a brief educational intervention administered during waiting room time can positively impact physician-child rapport and children's preference for an active role in health and their acquisition of medical information.", "A continuing medical education program was implemented and evaluated in 16 community hospitals. It was targeted at primary-care physicians and used physicians identified by their peers as being educationally influential for the dissemination of information. Self-study materials were used, followed by an intensive 2-wk preceptorship that resulted in a significant increase in physician knowledge. Inpatient chart audits identified a series of changes in the management of chronic obstructive pulmonary disease in the intervention hospitals that were not noted in the control hospitals. These included the increased use of intravenously administered fluids, loading doses of intravenously administered bronchodilators, aerosolized and single agent bronchodilators, and respiratory therapy services. Continuing medical education, delivered through community-based educationally influential physicians, is an effective way of changing physician behavior in small communities with no prior ongoing educational programs. This approach should improve patient care and may reduce the need for participation of academic faculty in traditional continuing education programs.", "Improving precision and economy in the prescribing of drugs is a goal whose importance has increased with the proliferation of new and potent agents and with growing economic pressures to contain health-care costs. We implemented an office-based physician education program to reduce the excessive use of three drug groups: cerebral and peripheral vasodilators, an oral cephalosporin, and propoxyphene. A four-state sample of 435 prescribers of these drugs was identified through Medicaid records and randomly assigned to one of three groups. Physicians who were offered personal educational visits by clinical pharmacists along with a series of mailed \"unadvertisements\" reduced their prescribing of the target drugs by 14 per cent as compared with controls (P = 0.0001). A comparable reduction in the number of dollars reimbursed for these drugs was also seen between the two groups, resulting in substantial cost savings. No such change was seen in physicians who received mailed print materials only. The effect persisted for at least nine months after the start of the intervention, and no significant increase in the use of expensive substitute drugs was found. Academically based \"detailing\" may represent a useful and cost-effective way to improve the quality of drug-therapy decisions and reduce unnecessary expenditures.", "An intervention was developed to increase patient involvement in care. Using a treatment algorithm as a guide, patients were helped to read their medical record and coached to ask questions and negotiate medical decisions with their physicians during a 20-minute session before their regularly scheduled visit. In a randomized controlled trial we compared this intervention with a standard educational session of equal length in a clinic for patients with ulcer disease. Six to eight weeks after the trial, patients in the experimental group reported fewer limitations in physical and role-related activities (p less than 0.05), preferred a more active role in medical decision-making, and were as satisfied with their care as the control group. Analysis of audiotapes of physician-patient interactions showed that patients in the experimental group were twice as effective as control patients in obtaining information from physicians (p less than 0.05). Results of the intervention included increased involvement in the interaction with the physician, fewer limitations imposed by the disease on patients' functional ability, and increased preference for active involvement in medical decision-making.", "Educational outreach visits are commonly used to promote changes in prescribing in family practice. However, the effectiveness of outreach visits has not been evaluated across a range of settings.\n To estimate the effectiveness of educational outreach visits on United Kingdom (UK) general practice prescribing and to examine the extent to which practice characteristics influenced outcome.\n Randomised controlled trial.\n General practices in 12 health authorities in England.\n Educational outreach visits were made to practices that received two of four guidelines. Each practice provided data on treatment of patients for all four guidelines for both pre and post-intervention periods. The primary outcome is average effect across all four guidelines. Secondary analyses examined the predictive effect of practice and guideline characteristics.\n Seventy per cent of practices approached agreed to take part in the intervention. Overall, educational outreach was associated with a significant improvement in prescribing practice (odds ratio [OR] = 1.24 [95% CI = 1.07 to 1.42]), a 5.2% (95% CI = 1.7% to 8.7%) increase in the number of patients treated within the guideline recommendations. Smaller practices (two or fewer full-time equivalent practitioners) responded much more favourably to educational outreach than larger practices. Smaller practices improved their performance in line with the guidelines by 13.5% (95% CI = 6% to 20.9%) attributable to outreach, while larger practices improved by only 1.4% (95% CI = -2.4% to 5.3%, P-value for interaction <0.001).\n In large practices, educational outreach alone is unlikely to achieve worthwhile change. There is good evidence to support the use of educational outreach visits in small practices.", "It is important for patients to provide relevant information to the doctor in consultation and to make their own information requirements known. This requires patients to actively participate in the process, something they appear to be reluctant to do. Earlier patient intervention studies have successfully manipulated patient involvement and question asking, although, the latter has tended to be accompanied by increased tension and negative impact. The present study uses a patient education leaflet which uses a wide definition of patient activation. It emphasizes the role of the 'good' patient as a provider of information extending beyond the recitation of symptoms to include insights to interpretation and meaning. Results showed that patients responded positively to the leaflet and a comparison of doctor ratings of communication quality showed the experimental group performed better than the controls. The findings are considered in terms of improved information exchange and the impact of making the 'rules' of consultation explicit is also discussed.", "To assess the effect of patient completed agenda forms for the consultation and doctors' education on identifying patients' agendas on the outcome of consultations.\n Randomised controlled trial.\n General practices in Leicestershire and Nottinghamshire, United Kingdom.\n 46 general practitioners and 976 patients.\n Education for general practitioners, with an embedded clustered randomised controlled trial of a patient agenda form.\n Number of problems identified, time required to manage each problem, duration of consultations, number of problems raised after the doctor considered the consultation finished (\"by the way\" questions), and patient satisfaction.\n Data were available from 45 doctors (98%) and 857 patients (88%). The number of problems identified in each consultation increased by 0.2 (95% confidence interval 0.1 to 0.4) with the agenda form, by 0.3 (0.1 to 0.6) with education, and by 0.5 (0.3 to 0.7) with both interventions. The time required to manage each problem was not affected. The duration of consultations with the agenda form was increased by 0.9 minutes (0.3 to 1.5 minutes) and with the combined intervention by 1.9 minutes (1.0 to 2.8 minutes). Patient satisfaction with the depth of the doctor-patient relationship was increased with the agenda form. The occurrence of \"by the way\" presentations did not change.\n A patient completed agenda form before the consultation or general practitioner education about the agenda form, or both, enabled the identification of more problems in consultations even though consultations were longer.", "Patient education is considered an important component of primary care medicine. The traditional methods of patient education have been physician-patient dialogue and printed handouts. This study compares the relative efficacy of pamphlets, one-to-one dialogue, and audiovisual presentations. The results indicate that the slide and sound presentation was most effective in conveying patient information.", "We conducted a randomized clinical trial to assess the effectiveness of a newly established education program for adults with asthma. The program was designed to improve patients' health and functional status. Hospitalized patients with asthma were randomly assigned to immediate education or a 6-month waiting list. The education program consisted of three group sessions, delivered by trained educators, and focused on improving patients' self-management skills. Of 253 eligible patients, 131 agreed to participate (66 assigned to immediate education, 65 controls) and 115 (88%) completed the follow-up assessment at 6 months. At follow-up, most indicators of self-management skills and health and functional status had improved significantly among educated patients, but similar improvements were also seen among controls. The trial arms differed significantly on only four variables: patients in the immediate-education group were more likely to develop confidence in their asthma treatment (odds ratio adjusted for baseline [OR] = 2.9; 95% confidence interval [CI]: 1.0 to 8.1), to improve their knowledge of correct inhalation technique (OR = 2.4; 95% CI: 1.0 to 5.7), and to improve knowledge of the peak flow reading that warrants calling a physician (OR = 3.1; 95% CI: 1.4 to 6.7), but they improved less on the Asthma Quality of Life Questionnaire \"activity\" score (difference: -0.4 on a 1 to 7 scale; 95% CI: -0.8 to 0.0). Use of health services during follow-up was similar in the two groups. The education program did not enhance patients' health and functional status, despite improving a few self-management skills. These results underscore the need for controlled evaluations of education programs.", "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.", "We investigated whether patient-centered communication skills can be taught to residents in Internal Medicine by using a time-limited behaviorally oriented intervention.\n Residents working at the Department of Internal Medicine were randomly assigned to an intervention group (IG; N = 19) or a control group (CG; N = 23). In addition to 6 hours of standard medical education per week, the IG received specific communication training of 22.5 hours duration within a 6-month period. Initially and 10 months later, participants performed interviews with simulated patients. Interviews were rated by blinded raters who used the Maastricht History and Advice Checklist-Revised.\n Compared with the CG, the IG improved substantially in many specific communication skills. Both groups improved in the \"amount of medical information identified\" and in the ability to \"communicate about feasibility of treatment.\"\n Patient-centered communication skills such as those presented in this intervention study can be taught. The ability to gain medical information and the readiness to communicate about aspects of medical treatment seem to improve with more professional experience; however, they also profit from the intervention.", "This investigation examined factors affecting patient involvement in consultations to decide local treatment for early breast cancer and the effectiveness of two methods of preconsultation education aimed at increasing patient participation in these discussions.\n Sixty patients with Stage I or II breast cancer (1) were pretested on their knowledge about breast cancer treatment and optimism for the future, (2) were randomly assigned to one of two methods for preconsultation education: interactive multimedia program or brochure, (3) completed knowledge and optimism measures, (4) consulted with a medical oncologist, radiation oncologist, and general surgeon, and (5) completed self-report measures assessing their involvement in the consultations and control over decision-making. The consultations were audiorecorded and analyzed to identify behavioral indicators of patient involvement (question-asking, opinion-giving, and expressing concern) and physician utterances encouraging patient participation.\n College-educated patients younger than 65 years of age were more active participants in these consultations than were older, less educated patients. In addition, patients showed more involvement when they interacted with physicians who encouraged and facilitated patient participation. The method of education did not affect patient involvement although patients tended to learn more about breast cancer treatment after using the multimedia program than after reading the brochure.\n Although patients vary in their expressiveness, physicians may be able to increase patient participation in deciding treatment by using patient-centered behavior. Also, preconsultation education appears to be an effective clinical strategy for helping patients gain an accurate understanding of their treatment options before meeting with physicians.", "We evaluated the effectiveness of a continuing medical education program, Physician Asthma Care Education, in improving pediatricians' asthma therapeutic and communication skills and patients' health care utilization for asthma.\n We conducted a randomized trial in 10 regions in the United States. Primary care providers were recruited and randomly assigned by site to receive the program provided by local faculty. The program included 2 interactive seminar sessions (2.5 hours each) that reviewed national asthma guidelines, communication skills, and key educational messages. Format included short lectures, case discussions, and a video modeling communication techniques. We collected information on parent perceptions of physicians' communication, the child's asthma symptoms, and patients' asthma health care utilization. We used multivariate regression models to determine differences between control and intervention groups.\n A total of 101 primary care providers and a random sample of 870 of their asthma patients participated. After 1 year, we completed follow-up telephone interviews with the parents of 731 of the 870 patients. Compared to control subjects, parents reported that physicians in the intervention group were more likely to inquire about patients' concerns about asthma, encourage patients to be physically active, and set goals for successful treatment. Patients of physicians that attended the program had a greater decrease in days limited by asthma symptoms (8.5 vs 15.6 days), as well as decreased emergency department asthma visits (0.30 vs 0.55 visits per year).\n The Physician Asthma Care Education program was used in a range of locations and was effective in improving parent-reported provider communication skills, the number of days affected by asthma symptoms, and asthma health care use. Patients with more frequent asthma symptoms and higher health care utilization at baseline were more likely to benefit from their physician's participation in the program.", "Patient education is an important part of asthma management. Individual education is usually used for this task. The object of this study was to assess whether another educational technique, educating patients in small groups, would be as effective and as acceptable as individual counselling in improving knowledge about asthma. A specially designed questionnaire was used to assess knowledge and other variables before and after education. Thirty-four patients were educated individually and 34 patients were educated in small groups. There were significant improvements in knowledge scores after both types of education. However group education took 4.5 hours for 34 patients whereas individual counselling took 14.25 hours for the same number. The results of this study suggest that educating patients in small groups is as effective as individual counselling in improving knowledge of asthma, is acceptable to patients and takes much less time.", "The aim of this experimental study was to evaluate the effectiveness of three patient-focused interventions designed to increase patient question asking in clinical consultations. Patients were randomly allocated to one of five conditions to receive either one of three interventions or to serve as an attention control group or a control group. The primary outcome measure was question asking by the patient of their physician. Participants in the intervention groups did not ask more questions than participants in the control groups. Immediately after the consultation participants in the intervention groups had higher levels of self-efficacy in asking questions. Three months after the index visit patients in the intervention groups were significantly more likely to be satisfied to some degree than patients in the control group. There was no difference in diabetic control. These results suggest that simple brief patient-focused interventions do not change patient behaviour in medical outpatient consultations.", "The costs and benefits of a planned patient education programme for patients with asthma were evaluated in a controlled trial. The patient education group received a planned patient education programme, performed by a physician, a pharmacist and a nurse over a 6-month period. Changes in the use of resources, productive output and in health status were measured for the patient education group and the control group. The total cost for planning, implementation and evaluation of the programme was 14074 British pounds sterling. The patient education group increased its contacts to general practitioners and the extra costs totalled 252 British pounds sterling. The increased costs of drugs used by the patient education group in the 6-month period was 2313 British pounds sterling compared with costs in the control group. The number of days lost through sickness decreased in the patient education group, corresponding to a 4528 British pounds sterling saving of otherwise lost earnings. The quality of life increased in the patient education group by 3.2 points on the Psychosomatic Discomfort Scale (2.9%). Health status increased by 38.9%. The study shows that the patient education programme has a positive clinical effect on the patient's quality of life and health status. The economic consequences of the implementation programme depend on the specific setup of the local healthcare system, where the programme is applied.", "Although patients with cancer are often accompanied by a relative during medical interviews, to the authors' knowledge little is known regarding the efficacy of communication skills training programs on physicians' communication skills in this context. The objective of the current study was to assess the efficacy of 6 consolidation workshops, 3 hours in length, that were conducted after a 2.5-day basic training program.\n After attending the basic training program, physicians were assigned randomly to consolidation workshops or to a waiting list. Training efficacy was assessed through simulated and actual interviews that were recorded on an audio tape at baseline, after consolidation workshops for the consolidation-workshops group, and 5 months after the end of basic training for the waiting-list group. Communication skills were assessed according to the Cancer Research Campaign Workshop Evaluation Manual. Patients' and relatives' perceptions of and satisfaction with physicians' communication performance were assessed using a 15-item questionnaire.\n Sixty-two physicians completed the training program. Compared with physicians who participated to the basic training program, when addressing the patient, physicians who were randomized to the consolidation workshops used more open, open directive, and screening questions (P = 0.011 in simulated patient interviews and P = 0.005 in actual patient interviews) and elicited and clarified psychologic concerns more often (P = 0.006 in simulated patient interviews and P < 0.001 in actual patient interviews). When they addressed the relative, physicians who were randomized to the consolidation workshops gave less premature information (P = 0.032 in simulated patient interviews and P < 0.001 in actual patient interviews). When they addressed the patient and the relative simultaneously, physicians who were randomized to the consolidation workshops used more empathy, educated guesses, alerting to reality, confronting, negotiating, and summarizing (P = 0.003 in simulated patient interviews and P = 0.024 in actual patient interviews). Patients, but not relatives, who interacted with physicians in the consolidation-workshops group were more satisfied globally with the interviews (P = 0.022).\n Six 3-hour consolidation workshops resulted in improved communication skills addressed to patients and to relatives. The current results showed that the transfer of skills addressing relatives' concerns remained limited and that consolidation workshops should focus even more systematically on the practice of three-person interviews.", "Two different patient education programmes for asthma in general practice were evaluated in a controlled trial. Knowledge, self management, and morbidity due to asthma were assessed in 339 patients by means of a questionnaire. One group then received a maximum education programme, a second group received a limited education programme, and a third acted as a control group. 274 patients were reassessed after one 1 year. In both the intervention groups, understanding of asthma was greater after the trial. Only in the maximum intervention group was a significant improvement in knowledge of asthma shown. Neither group showed any change in self-management ability or asthma morbidity that differed significantly from changes in the control group. These simple informational education programmes were ineffective when applied to a general practice population. Further studies of factors affecting attitudes, beliefs, and actions are needed to improve the advice and support given to asthma patients.", "To determine whether an intervention designed to improve patient-physician communication increases the frequency with which physicians elicit patients' concerns, changes other communication behaviors, and improves health care outcomes.\n Pretest-posttest design with random assignment of physicians to intervention or control groups.\n General medicine clinics of a university-affiliated Veterans Affairs Hospital.\n Forty-two physicians and 348 continuity care patients taking prescription medications for chronic medical conditions.\n Intervention group physicians received 4.5 hours of training on eliciting and responding to patients' concerns and requests, and their patients filled out the Patient Requests for Services Questionnaire prior to a subsequent clinic visit. Control group physicians received 4.5 hours of training in medical decision-making.\n The frequency with which physicians elicited all of a patient's concerns increased in the intervention group as compared with the control group (p = .032). Patients perceptions of the amount of information received from the physician did increase significantly (p < .05), but the actual magnitude of change was small. A measure of patient satisfaction with the physicians was high at baseline and also showed no significant change after the intervention. Likewise, the intervention was not associated with changes in patient compliance with medications or appointments, nor were there any effects on outpatient utilization.\n A low-intensity intervention changed physician behavior but had no effect on patient outcomes such as satisfaction, compliance, or utilization. Interventions may need to focus on physicians and patients to have the greatest effect.", "To establish the effect of an educational intervention for general practitioners on the health behaviours and wellbeing of elderly patients.\n Randomised controlled trial with 1 year follow up.\n Metropolitan general practices in Melbourne, Australia.\n 42 general practitioners and 267 of their patients aged over 65 years.\n Educational and clinical practice audit programme for general practitioners on health promotion for elderly people.\n Patients' physical activity, functional status, self rated health, immunisation status, social contacts, psychological wellbeing, drug usage, and rate of influenza vaccination. Primary efficacy variables were changes in outcome measures over 1 year period.\n Patients in the intervention group had increased (a) walking by an average of 88 minutes per fortnight, (b) frequency of pleasurable activities, and (c) self rated health compared with the control group. No change was seen in drug usage, rate of influenza vaccination, functional status, or psychological wellbeing as a result of the intervention. Extrapolations of the known effect of these changes in behaviour suggest mortality could be reduced by 22% if activity was sustained for 5 years.\n Education of the general practitioners had a positive effect on health outcomes of their elderly patients. General practitioners may have considerable public health impact in promotion of health for elderly patients.", "A continuing medical education (CME) program in rheumatoid arthritis was implemented and evaluated in six community hospitals. It was targeted at primary care physicians and utilized physicians identified by their peers as being educationally influential for the dissemination of content knowledge. Although inpatient and outpatient audits of physician records demonstrated little change in three control communities, substantial improvement in the utilization of diagnostic procedures and patient management was documented in the three intervention communities utilizing the influential physicians. CME delivered through community-based educationally influential physicians is an effective way to change physician behavior in small communities with no prior ongoing educational programs. This approach should improve the primary care given to patients with rheumatoid arthritis and reduce the need for participation of academic faculty in traditional CME programs.", "Although there is wide recognition of the usefulness of improving physicians' communication skills, no studies have yet assessed the efficacy of post-training consolidation workshops. This study aims to assess the efficacy of six 3-hour consolidation workshops conducted after a 2.5-day basic training program.\n Physicians, after attending the basic training program, were randomly assigned to consolidation workshops or to a waiting list. Training efficacy was assessed through simulated and actual patient interviews that were audiotaped at baseline and after consolidation workshops for the consolidation-workshop group, and approximately 5 months after the end of basic training for the waiting-list group. Communication skills were assessed according to the Cancer Research Campaign Workshop Evaluation Manual. Patients' perceptions of communication skills improvement were assessed using a 14-item questionnaire.\n Sixty-three physicians completed the training program. Communication skills improved significantly more in the consolidation-workshop group compared with the waiting-list group. In simulated interviews, group-by-time repeated measures analysis of variance showed a significant increase in open and open directive questions (P =.014) and utterances alerting patients to reality (P =.049), as well as a significant decrease in premature reassurance (P =.042). In actual patient interviews, results revealed a significant increase in acknowledgements (P =.022) and empathic statements (P =.009), in educated guesses (P =.041), and in negotiations (P =.008). Patients interacting with physicians who benefited from consolidation workshops reported higher scores concerning their physicians' understanding of their disease (P =.004).\n Consolidation workshops further improve a communication skills training program's efficacy and facilitate the transfer of acquired skills to clinical practice.", "Family psychoeducation has a well-documented effect on the short-term prognosis in schizophrenia. Less is known about the effectiveness of shorter programmes with the main focus on information for patients (patient education) or for patients and relatives (family education).\n A randomized study of the effectiveness of an eight-session psychoeducational programme for patients with schizophrenia and for their relatives was conducted in two community mental health centres, in Arhus and Viborg (Denmark). Patient outcome measures were knowledge, relapse, compliance, insight and satisfaction, and relative outcome measures were knowledge and satisfaction. Post-intervention outcome and follow-up evaluation 1 year after the start of the intervention are presented.\n A statistically significant increase in knowledge of schizophrenia in both relatives and patients was demonstrated at postintervention and a non-significant trend at 1-year follow-up. Statistically significant changes in the Verona Service Satisfaction Scale Scores in the subdimension of satisfaction with Relatives involvement were demonstrated both for patients and relatives postintervention and for patients at 1-year follow-up. There was a tendency that time-to-relapse increased in the intervention group at postintervention and that the schizophrenia subscore of the Brief Psychiatric Rating Scale was reduced in the intervention group at 1-year follow-up. No differences were found between the groups regarding compliance, insight into psychosis, psychosocial function (General Assessment of Function) or in relatives' expressed emotion scores postintervention or at 1-year follow-up.\n A short patient and relative education programme seems to be able to influence knowledge and some aspects of satisfaction, but does not seem to be sufficient to influence important variables such as relapse, compliance, psychopathology, insight or psychosocial functioning.", "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.", "Previous work has indicated a high rate of non-attendance at hospital based clinics among young, multiracial asthmatic patients of lower socioeconomic class. The efficacy of delivering asthma education from a community health centre established in a multiracial working class neighbourhood was evaluated.\n A prospective controlled study was performed in which asthmatic subjects aged between two and 55 years attending a hospital emergency room with acute asthma and living within a defined geographical area of high emergency room users were randomised to the usual follow up or the education centre plus usual follow up. Measurements were taken at entry into the study and again nine months later.\n At nine months patients randomised to the education centre had more preventive medications, more peak expiratory flow meters and better flow meter technique, more self-management plans, better knowledge of appropriate action to take when confronted with worsening asthma, less nocturnal awakening, and better self-reported asthma control than the control group. There was no difference between the study groups in measurements of compliance, hospital admission, days lost from school or work, or emergency room use.\n The main effects of education were on asthma knowledge and self-management skills, whilst improvements in asthma morbidity were small. Potential reasons for this include heterogeneous study population (in terms of baseline self-management skills, asthma severity, ethnicity and age), pragmatic study design, insensitivity of many of the measurements of morbidity, the modest effectiveness of a single time limited education programme, and inability to limit the effects of such a large community based study to the intervention group (there was a 67% reduction in asthma admissions during the study period from the geographical area targeted compared with a 22% reduction for the rest of Auckland).", "Although substantial resources have been invested in communication skills training for clinicians, little research has been done to test the actual effect of such training on patient satisfaction.\n To determine whether clinicians' exposure to a widely used communication skills training program increased patient satisfaction with ambulatory medical care visits.\n Randomized, controlled trial.\n A not-for-profit group-model health maintenance organization in Portland, Oregon.\n 69 primary care physicians, surgeons, medical subspecialists, physician assistants, and nurse practitioners from the Permanente Medical Group of the Northwest.\n \"Thriving in a Busy Practice: Physician-Patient Communication,\" a communication skills training program consisting of two 4-hour interactive workshops. Between workshops, participants audiotaped office visits and studied the audiotapes.\n Change in mean overall score on the Art of Medicine survey (HealthCare Research, Inc., Denver, Colorado), which measures patients' satisfaction with clinicians' communication behaviors, and global visit satisfaction.\n Although participating clinicians' self-reported ratings of their communication skills moderately improved, communication skills training did not improve patient satisfaction scores. The mean score on the Art of Medicine survey improved more in the control group (0.072 [95% CI, -0.010 to 0.154]) than in the intervention group (0.030 [CI, -0.060 to 0.1201).\n \"Thriving in a Busy Practice: Physician-Patient Communication,\" a typical continuing medical education program geared toward developing clinicians' communication skills, is not effective in improving general patient satisfaction. To improve global visit satisfaction, communication skills training programs may need to be longer and more intensive, teach a broader range of skills, and provide ongoing performance feedback.", "Compliance with physician recommendations among long-term hypertensive patients can be a chronic and difficult treatment problem. This study evaluated the relative effectiveness of additional patient education and psychosocial counseling in improving patient compliance. At a family practice clinic, 123 low income, rural, black hypertensive patients were pretested on several psychological characteristics and randomly assigned to one of three groups: vigorous, group patient education and family physician appointments; supportive, individualized psychosocial counseling and family physician appointments; or family physician appointments only, which was the baseline medical care. Intervention and follow-up each lasted three months, and the intervention was in addition to the patients' baseline medical care. Compliance was measured by: keeping follow-up appointments; bringing antihypertension medications to each appointment; consuming these medications; and diastolic blood pressure. Analysis of variance of group mean and change scores, t tests, and chisquare analysis indicated that neither additional patient education nor additional psychosocial counseling improved compliance or blood pressure control significantly better than regular family physician visits alone.", "Paternalistic models of health care, social distance between patients and providers, and cultural norms discourage patients from playing an active role in health consultations. This study tested whether individual coaching can give family planning patients the confidence and communication skills to talk more openly and more vigorously with providers. Educators met with 384 Indonesian women in clinic waiting rooms and coached them on asking questions, expressing concerns, and seeking clarification. An analysis of audiotaped consultations found that patients who received coaching articulated significantly more questions and concerns than others. Coaching narrowed differentials in active communication by patient type, age, and assertiveness, but it widened differentials by patient education and socioeconomic class. The discontinuation rate at 8 months was lower in the intervention than the control condition, but the difference was only marginally significant.", "No evidence addresses the effectiveness of patient-centered cultural competence training in non-Western settings.\n To examine whether a patient-centered cultural competency curriculum improves medical students' skills in eliciting the patients' perspective and exploring illness-related social factors.\n Fifty-seven medical students in Taiwan were randomly assigned to either the control (n = 27) or one of two intervention groups: basic (n = 15) and extensive (n = 15). Both intervention groups received two 2-hour patient-centered cultural competency workshops. In addition, the extensive intervention group received a 2-hour practice session. The control group received no training.\n At the end of the clerkship, all students were evaluated with an objective structured clinical examination (OSCE). Students in the extensive intervention group scored significantly higher than the basic intervention and control groups in eliciting the patient's perspective (F = 18.38, p < 0.001, eta(2) = 0.40). Scores of both intervention groups were significantly higher than the control group in the exploring social factors (F = 6.66, p = 0.003, eta(2) = 0.20).\n Patient-centered cultural competency training can produce improvement in medical students' cross-cultural communication skills in non-Western settings, especially when adequate practice is provided.", "To evaluate the impact on clinical behavior of a 3-day workshop designed to increase trainees' rates of smoking cessation counseling and reminders about Pap smears in routine consultations.\n Randomized control trial.\n Accredited teaching practices of the Royal Australian College of General Practitioners' Training Program.\n Thirty-four trainees and 1,500 consecutive adult patients ages 16-65 years.\n Trainees randomly allocated to the experimental group participated in a 3-day interactive workshop on disease prevention during their 13-week family medicine term. Audiotapes of consultations with adults conducted by trainees at the beginning and end of the rotation were analyzed blind to compare assessment of patients' smoking status and, for women, date of last Pap smear. A questionnaire mailed to each patient after the consultation also allowed identification of smokers and women overdue for a smear. Consultations with these patients at risk were analyzed for preventive counseling. Inter- and intrarater reliability was calculated for audiotape analysis.\n Preworkshop rates of questions about smoking were low, occurring in 22% of consultations. While trainees allocated to the experimental workshop were more likely to ask a routine question about smoking at the end of the term than those in the control group (P = 0.01), two-thirds of smokers remained undetected irrespective of trainee group and fewer than one in five were advised to stop smoking. Reminders about Pap smears did not change as a result of training and remained low in fewer than 20% of consultations. kappa values demonstrated high reliability of audiotape analysis.\n This direct measurement of clinical behavior revealed that low levels of preventive care provided by trainees are resistant to skills training without reinforcement in clinical practice. In view of the importance of prevention in routine consultations, we recommend continued evaluation of more intensive educational programs. Those withstanding rigorous evaluation could be considered for implementation in similar training contexts seeking to improve the frequency and quality of disease prevention in primary medical care.", "To compare three approaches for marketing a quit smoking intervention kit to general practitioners.\n Randomised trial of (a) personal delivery and presentation by an educational facilitator with a follow up visit six weeks later; (b) delivery to the receptionist by a friendly volunteer courier with a follow up phone call six weeks later, or (c) postal delivery with a follow up letter six weeks later.\n Melbourne, Australia.\n 264 randomly selected general practitioners.\n A research assistant visited each doctor four months after delivery and measured use of components of the kit. A questionnaire measuring perceptions of aspects of the kit and its delivery was completed by doctors. Costs of each approach were calculated.\n Doctors receiving the educational facilitator approach were significantly more likely than those receiving the other two approaches to have seen the kit, to rate the method of delivery as engendering motivation to try the kit, to have used one of the \"intensive intervention\" components from the kit, to report that they found the kit less complicated, and to report greater knowledge of how to use the kit. There were no significant differences in use of \"minimal intervention\" components of the kit, ratings of overall acceptability of delivery, perceptions of cultural and structural barriers to using the kit, and ratings of the overall acceptability of the kit. The cost of the educational facilitator approach ($A142/doctor) was 24 times that of the mailed approach. The volunteer courier approach ($A14) was twice the cost of the mailed approach.\n Educational facilitators and volunteer couriers do not seem to be cost effective strategies for distributing smoking interventions.", "We examined the effectiveness of a training program for physician-delivered nutrition counseling, alone and in combination with a structured office practice environment for nutrition management, on physicians' counseling practices. Forty-five primary care internists and 1,278 of their patients in the top quarter of the cholesterol distribution at a central Massachusetts health maintenance organization (the Fallon Clinic) were enrolled into a randomized controlled trial. Physicians were randomized by site into three conditions: (1) usual care, (2) physician nutrition counseling training, and (3) physician nutrition counseling training plus a structured office practice environment for nutrition management (prompts and the provision of lipid results and counseling algorithms). A randomly selected 325 patients were given a 10-item patient exit interview (PEI) assessing whether the physician provided advice; assessed past changes, barriers, and resources; negotiated specific plans and goals; provided patient materials; referred the patient to a dietitian; and developed plans for follow-up. Condition 3 physicians demonstrated significantly greater implementation of the nutrition counseling sequence than did physicians in either of the other two conditions (P < .0001). Referrals to nutrition services were markedly reduced in condition 2, despite PEI scores no different than those in condition 1. Higher PEI scores for patients seen by physicians in condition 3 were stable for as long as two years beyond training. Primary care internists, when provided with both training in counseling techniques and a supportive office environment, will carry out patient counseling appropriately. Training alone, however, is not sufficient and may be counterproductive. Medical Subject Headings (MeSH): hypercholesterolemia, diet therapy, coronary disease, health behavior, primary health care, medical education, managed care programs.", "Doctor-patient communication is an essential component of general practice. Improvement of GPs' communication patterns is an important target of training programmes. Available studies have so far failed to provide conclusive evidence of the effectiveness of educational interventions to improve doctor-patient communication.\n To examine the effectiveness of a learner-centred approach that focuses on actual needs, to improve GPs' communication with patients.\n Randomised controlled trial.\n One hundred volunteer GPs in the Netherlands.\n The intervention identified individual GPs' deficiencies in communication skills by observing authentic consultations in their own surgery. This performance assessment was followed by structured activities in small group meetings, aimed at remedying the identified shortcomings. Outcomes were measured using videotaped consultations in the GPs' own surgery before and after the intervention. Communication skills were rated using the MAAS-Global, a validated checklist.\n The scores in the intervention group demonstrated a significant improvement compared with those of the control group (95% confidence interval = 0.04 to 0.75). The effect size was moderate to large (d-value = 0.66). The level of participation significantly contributed to the effectiveness. Largest improvement was found on patient-centred communication skills.\n The approach of structured individual improvement activities based on performance assessment is more effective in improving communication skills than current educational activities.", "To investigate the effectiveness of a quality improvement educational program in rural hospitals.\n Hospital-randomized controlled trial.\n \n A total of 47 rural and small community hospitals in Texas that had previously received a web-based benchmarking and case-review tool.\n The 47 hospitals were randomized either to receive formal quality improvement educational program or to a control group. The educational program consisted of two 2-day didactic sessions on continuous quality improvement techniques, followed by the design, implementation and reporting of a local quality improvement project, with monthly coaching conference calls and annual follow-up conclaves.\n Performance on core measures for community-acquired pneumonia and congestive heart failure were compared between study groups to evaluate the impact of the educational program.\n No significant differences were observed between the study groups on any measures. Of the 23 hospitals in the intervention group, only 16 completed the didactic program and 6 the full training program. Similar results were obtained when these groups were compared with the control group.\n While the observed results suggest no incremental benefit of the quality improvement educational program following implementation of a web-based benchmarking and case-review tool in rural hospitals, given the small number of hospitals that completed the program, it is not conclusive that such programs are ineffective. Further research incorporating supporting infrastructure, such as physician champions, financial incentives and greater involvement of senior leadership, is needed to assess the value of quality improvement educational programs in rural hospitals.", "To evaluate family physicians' enjoyment of and knowledge gained from game-based learning, compared with traditional case-based learning, in a continuing medical education (CME) event on stroke prevention and management.\n An equivalence trial to determine if game-based learning was as effective as case-based learning in terms of attained knowledge levels. Game questions and small group cases were developed. Participants were randomized to either a game-based or a case-based group and took part in the event.\n Ontario provincial family medicine conference.\n Thirty-two family physicians and 3 senior family medicine residents attending the conference.\n Participation in either a game-based or a case-based CME learning group.\n Scores on 40-item immediate and 3-month posttests of knowledge and a satisfaction survey.\n Results from knowledge testing immediately after the event and 3 months later showed no significant difference in scoring between groups. Participants in the game-based group reported higher levels of satisfaction with the learning experience.\n Games provide a novel way of organizing CME events. They might provide more group interaction and discussion, as well as improve recruitment to CME events. They might also provide a forum for interdisciplinary CME. Using games in future CME events appears to be a promising approach to facilitate participant learning.", "Evidence is sparse concerning the value of the \"educational\" materials that physicians receive in the mail. We conducted a randomized trial of a mailed continuing education program on hypertension for primary care physicians. Although formal pretesting documented that the program led to significant improvements in physician knowledge over the short term, the current study showed no lasting effect on physician knowledge (mean scores on an end-of-study questionnaire were 50% and 52% for study and control physicians, respectively) and no influence on performance in lowering the blood pressures of patients referred from screening (mean blood pressure drop for study patients, 12.2/10.4 mm Hg vs 13.0/10.6 mm Hg for control patients). The chance that we missed a difference in diastolic blood pressure as great as 3 mm Hg is less than 5%. Resources spent on instructional materials mailed to physicians may be wasted.", "Increases in patient participation in medical interactions have been achieved to date using structured waiting-room interviews. In this pilot study, a printed intervention was tested as an inexpensive alternative with potential for wider dissemination. Sixty-seven family medicine patients were assigned randomly to one to two educational conditions just prior to their medical visit: a treatment booklet stressing the importance of recognizing information needs and encouraging patients to ask questions; or a placebo education booklet similar in format but not in content. The patient-physician interactions were audiotaped to determine the number of questions patients asked, and a questionnaire was administered after each encounter to assess patient satisfaction with care. The mean numbers of questions asked in the experimental and control groups were 7.46 and 5.63, respectively; the mean difference of 1.83 questions was statistically non-significant (P greater than 0.05). Question-asking did not correlate with reported satisfaction. Suggestions for modification to this research approach are presented.", "Community pharmacists have increasing involvement in the self-management of minor illness as a result of the availability of a wider range of over-the-counter (OTC) medicines. We undertook a randomized controlled trial (RCT) to assess the effectiveness and efficiency of educational strategies to implement evidence-based guidelines for the sale of OTC anti-fungals in the community pharmacy setting.\n The aim of the study was to compare the effectiveness and efficiency of two guideline dissemination strategies in community pharmacy settings.\n A 2 x 2 factorial, cluster RCT was conducted with 60 community pharmacies in the Grampian region of Scotland. The interventions included dissemination of an evidence-based guideline for OTC management of vulvovaginal candidiasis (thrush) by postal dissemination (control), educational outreach visit or attendance at a continuing professional education session. Pre- and post-intervention simulated patient visits were made to participating pharmacies. The simulated patients completed assessment forms following each visit. The primary outcome was the appropriateness (based upon the guidelines) of sale or no sale of OTC anti-fungals.\n There were no significant differences in the proportion of appropriate outcomes following educational outreach [odds ratio (OR) = 1.1; 95% confidence interval (CI) 0.52 to 2.45] or continuing professional education (OR = 0.88; 95% CI 0.41 to 1.91).\n Neither strategy was effective in improving the appropriateness of OTC management of vulvovaginal candidiasis by community pharmacy staff. Further research is needed to identify barriers to guideline implementation and evidence-based practice in this setting.", "When patients are active participants in discussions, comprehension and compliance are likely to improve. This study examines the use of two interventions to aid patients in initiating such discussions in the area of health maintenance.\n The study was a randomized controlled trial of adult patients. The first intervention used two cards that listed seven core health maintenance concerns. The second intervention used a brief session with a nurse to help patients identify their health risks and develop a plan for seeking any desired information about these risks. An exit questionnaire and a telephone interview 4 to 6 weeks later assessed the extent to which (1) information seeking by patients was stimulated; (2) patients recalled the information obtained; (3) patients used the information to effect lifestyle changes; and (4) patients felt they participated in the decision to discuss health maintenance.\n Both interventions stimulated patients to request health maintenance information (both P < .05); the second intervention significantly increased patient recall (P = .018). Neither intervention, however, had a significant impact on lifestyle change or sense of participation in the decision to initiate discussion. Analysis of the second intervention did show that both increasing patients' recall of information (P = .008) and sense of involvement in the decision to discuss health maintenance (P = .003) significantly increases the likelihood of lifestyle change.\n Two interventions have been developed that are relatively simple and inexpensive methods to stimulate patients to seek health maintenance, and quite probably other health-related information. The blunted impact of these two interventions, however, raises the question of whether such simple and relatively inexpensive interventions are strong enough to stimulate patients to use this information to initiate change when one seeks to address a wide range of risks.", "To determine if a simple educational intervention can increase resident physician literature search activity.\n Randomized controlled trial.\n University hospital-based internal medicine training program.\n Forty-eight medical residents rotating on the general internal medicine service.\n One-hour didactic session, the use of well-built clinical question cards, and practical sessions in clinical question building.\n Objective data from the library information system that included the number of log-ons to medline, searching volume, abstracts viewed, full-text articles viewed, and time spent searching. Median search activity as measured per person per week (control vs intervention): number of log-ons to medline (2.1 vs 4.4, P <.001); total number of search sets (24.0 vs 74.2, P <.001); abstracts viewed (5.8 vs 17.7, P=.001); articles viewed (1.0 vs 2.6, P=.005); and hours spent searching (0.8 vs 2.4, P <.001).\n A simple educational intervention can markedly increase resident searching activity.", "Two interventions designed to help physicians manage hypertensive patients were evaluated in a controlled trial: 1) computer-generated feedback to facilitate identification of poorly controlled patients; and 2) a physician education program on clinical management strategies, emphasizing patient compliance. Four physician practice teams received either computer feedback, the education program, both, or neither. Feedback team physicians received seven monthly listings of the latest visits and blood pressures of their hypertensive patients. The self-administered learning program included written clinical stimulations and associated didactic material. Experimental and control physicians were similar in baseline knowledge, patient mix and level of training. All feedback team physicians requested appointments for listed patients, and their patients made twice as many visits as control patients during the intervention period (p less than 0.05). Education team physicians showed significant gains on a content-specific post-intervention test: mean score 84 per cent compared with 74 per cent for the control group (p less than 0.005). All patient groups showed improvement in blood pressure over the study period. However, no differences between intervention teams could be detected (p greater than 0.20). The probability of missing a 10 mm interteam difference in outcome diastolic pressure was 1 per cent (power of 0.99). Strategies for further improvement in outpatient hypertension management may need to come from outside the traditional medical model.", "Sustaining patient motivation for long-term adherence to drug therapies remains a substantial problem for physicians, other health care providers, the patients themselves, and their families. Other therapeutic requests such as dietary changes and weight control may be even more difficult to maintain than taking pills. As part of a controlled experimental design implemented in an outpatient teaching hospital, an educational program was implemented to improve family member support for medical compliance among hypertensive patients. Family members were interviewed, counseled, and provided with a booklet for the purpose of educating and involving them in the home management of high blood pressure. The booklet identified ways the family member could assist the patient with medication compliance, appointment keeping, as well as diet and weight control. These items were identified and recorded as behavioral objectives in the booklet. Patients were followed for three years to assess long-term outcomes. Results showed a strong statistically significant difference between the experimental and control groups, with the experimental group demonstrating higher levels of appointment-keeping behavior, weight control, and BP under control (all p values less than .001). Analysis of the main effects of the educational program demonstrated that the family member support intervention accounted for the greatest decrease in diastolic blood pressure variability, R2 = .20, p less than .001.", "The aim of the present study was to determine the impact of a nurse-led support and education programme for improving the spouses' perceived general quality of life, life situation, general well-being and health state.\n Stroke is a disease with great consequences for the patients and their families. The spouses often feel obligated to care for the patient, providing psychological and physical support and having to cope with the patient's physical and cognitive impairments. This might lead to increased problems, as family members struggle to adapt to their new roles and responsibilities.\n Longitudinal, randomized controlled trial. One hundred spouses were randomly assigned to intervention or control groups, 50 in each group. The intervention group participated in a support and education programme, six times during six months, led by stroke specialist nurses. Both groups were followed for 12 months.\n No significant differences were found, between intervention and control groups, over time. In the sub analyses, we found that the group attending 5-6 times had a significant decrease in negative well-being and increased quality of life over time, while the group attending fewer times had a significant decrease in positive well-being and health state, similar to the control group, which also had a significant decrease in negative and general well-being.\n A support and education programme might have a positive effect on spouses' well-being, on condition that they attend at least five times.\n To facilitate the spouses' role as informal caregivers to the stroke patients, further development of the support and education programme used in the present study is needed, including empowerment approach and implementation of coping strategies.", "High re-attendance rates are common after asthma emergency department (ED) care. Inadequate patient education has been cited as a potential cause of re-attendance and the optimal format of education is uncertain. The present study aimed to compare the effectiveness of patient-centred education (PCE) and standard asthma patient education on ED re-attendance. A randomised controlled trial was conducted at two inner-city Australian teaching hospitals' EDs, where patients received either standard patient education (SPE) or PCE. Both groups received a six-topic curriculum. However, PCE patients reordered the topics according to their own priority and thus controlled the order of education. In total, 146 adult patients presenting to EDs with acute asthma were enrolled. After 4 months, ED re-attendance decreased from 22 to 12% in the PCE group and remained unchanged in the SPE group (between group odds ratio 0.4, 95% confidence interval (0.2-1.1)). In 78 patients discharged after ED care, the PCE group had fewer re-attendances after 4 and 12 months (0.3 (0.1-0.9) and 0.3 (0.1-0.8), respectively ). PCE patients with no general practitioner care in the preceding 7 days had fewer re-attendances after 4 and 12 months (0.1 (0.0-0.7) and 0.2 (0.0-0.6), respectively). A trend of better asthma control was evident, with a reduction in activity limitation. In conclusion, patient-centred education offers promise as a brief education process in the emergency department. However, a large multicentre trial of patient-centred education is required.", "Shared decision-making (SDM) between professionals and patients is increasingly advocated from ethical principles. Some data are accruing about the effects of such approaches on health or other patient-based outcomes. These effects often vary substantially between studies.\n Our aim was to evaluate the effects of training GPs in SDM, and the use of simple risk communication aids in general practice, on patient-based outcomes.\n A cluster randomized trial with crossover was carried out with the participation of 20 recently qualified GPs in urban and rural general practices in Gwent, South Wales. A total of 747 patients with known atrial fibrillation, prostatism, menorrhagia or menopausal symptoms were invited to a consultation to review their condition or treatments. After baseline, participating doctors were randomized to receive training in (i) SDM skills; or (ii) the use of simple risk communication aids, using simulated patients. The alternative training was then provided for the final study phase. Patients were randomly allocated to a consultation during baseline or intervention 1 (SDM or risk communication aids) or intervention 2 phases. A randomly selected half of the consultations took place in 'research clinics' to evaluate the effects of more time for consultations, compared with usual surgery time. Patient-based outcomes were assessed at exit from consultation and 1 month follow-up. These were: COMRADE instrument (principal measures; subscales of risk communication and confidence in decision), and a range of secondary measures (anxiety, patient enablement, intention to adhere to chosen treatment, satisfaction with decision, support in decision making and SF-12 health status measure). Multilevel modelling was carried out with outcome score as the dependent variable, and follow-up point (i.e. exit or 1 month later for each patient), patient and doctor levels of explanatory variables.\n No statistically significant changes in patient-based outcomes due to the training interventions were found: COMRADE risk communication score increased 0.7 [95% confidence interval (CI) -0.92 to 2.32] after risk communication training and 0.9 (95% CI -0.89 to 2.35) after SDM training; and COMRADE satisfaction with communication score increased by 1.0 (95% CI -1.1 to 3.1) after risk communication, and decreased by 0.6 (95% CI 2.7 to -1.5) after SDM training. Patients' confidence in the decision (2.1 increase, 95% CI 0.7-3.5, P < 0.01) and expectation to adhere to chosen treatments (0.7 increase, 95% CI 0.04-1.36, P < 0.05) were significantly greater among patients seen in the research clinics (when more time was available) compared with usual surgery time. Most outcomes deteriorated between exit and 1 month later. There was no interaction between intervention effects.\n Patients can be more involved in treatment decisions, and risks and benefits of treatment options can be explained in more detail, without adversely affecting patient-based outcomes. SDM and risk communication may be advocated from values and ethical principles even without evidence of health gain or improvement in patient-based outcomes, but the resources required to enhance these professional skills must also be taken into consideration. These data also indicate the benefits of extra consultation time.", "Examined a simple intervention to improve the patient's contribution to communication in a medical office visit. In the first study, women awaiting a medical appointment were randomly assigned either to a group that was asked to list three questions to ask their physician or to a control group. Women who listed questions asked more questions in the visit and reported being less anxious. In the second study, a third group that received a message from their physician encouraging question asking was added. Both experimental groups asked more of the questions they had wished to, had greater feelings of control, and were more satisfied with the visit in general and with the information they received. The two experimental groups did not differ significantly, suggesting that the effect may be attributed either to thinking one's questions out ahead of time or to the perception that one's physician is open to questions.", "Only 3 to 5% of new adult cancer patients participate in clinical trials nationwide. The lack of knowledge and awareness about clinical trials is a significant barrier to clinical trials participation. A randomized trial was conducted to test the effect of an educational video on positively changing patients' knowledge and attitudes regarding clinical trials and thereby increasing enrollment rates.\n Lung cancer patients were randomized to viewing either an 18-minute video about clinical trials before first clinic appointment or to standard care. Participants completed a baseline and 2-week postintervention survey to assess their knowledge and attitudes toward trials participation. Fisher's exact test tests, t tests, and regression were used to compare patient characteristics and outcomes between arms.\n Of 145 subjects randomized, 126 (63/arm) satisfied all inclusion criteria and were included in the analysis. A linear regression showed that the video intervention was significantly associated with patients' self-assessed likelihood to enroll score measured at 2-week follow-up (p = 0.019). Although statistically insignificant, enrollment rates were found to be higher in the intervention arm for therapeutic trials alone (17.5% versus 11.1%) and for therapeutic and nontherapeutic trials combined (25.4% versus 15.9%).\n The brief educational video seems to be effective in positively changing lung cancer patients' attitudes about participation in clinical trials. Higher enrollment rates were also observed in the intervention group but the differences did not reach statistical significance. These findings suggest a potential impact of the educational video on clinical trial enrollment; however, larger studies are needed to confirm these findings.", "Due to worldwide migration to Western countries, physicians are increasingly encountering patients with different ethnic backgrounds. Communication problems can arise as a result of differences in cultural backgrounds and poor language proficiency.\n To assess the effectiveness of an educational intervention on intercultural communication aimed to decrease inequalities in care provided between Western and non-Western patients.\n A randomised controlled trial with randomisation at the GP level and outcome measurements at the patient level.\n General practice in Rotterdam.\n Thirty-eight Dutch GPs in the Rotterdam region, with at least 25% of inhabitants of non-Western origin, and 2407 visiting patients were invited to participate in the study. A total of 986 consultations were finally included. The GPs were educated about cultural differences and trained in intercultural communication. Patients received a videotaped instruction focusing on how to communicate with their GP in a direct way. The primary outcome measure was mutual understanding and the secondary outcomes were patient's satisfaction and perceived quality of care. The intervention effect was assessed for all patients together, for the 'Western' and 'non-Western' patients, and for patients with different cultural backgrounds separately.\n An intervention effect was seen 6 months after the intervention, as improvement in mutual understanding (and some improvement in perceived quality of care) in consultations with 'non-Western' patients.\n A double intervention on intercultural communication given to both physician and patient decreases the gap in quality of care between 'Western' and 'non-Western' patients.", "Previous evaluations of continuing medical education (CME) have yielded conflicting results regarding its effects on physician knowledge, performance, and subsequent patient outcomes. Poor adherence by mothers to prescribed pediatric regimens is a separate, but well-documented, problem. In the present study we assessed the ability of CME to: (1) increase the knowledge of pediatricians about compliance-enhancing strategies; (2) increase the performance of these practices by pediatricians; and (3) improve mothers' compliance with antibiotic regimens for their children's otitis media. Ninety pediatricians were randomly assigned to either a control group or one of two CME interventions: tutorial plus printed materials or mailed printed materials only. Following the interventions, data on compliance and on reported behaviors of pediatricians were gathered from a random sample of mothers (N = 771) whose children were being treated for otitis media. Findings indicated that CME increased physician knowledge and compliance-enhancing practices and resulted in improvement in mothers' adherence to therapy.", "The authors evaluated the effect of an educational and feedback intervention on H2-blocker prescribing patterns and determined, if such effects differed for network- versus group-model health maintenance organization (HMO) physicians and in academic versus nonacademic settings. Physicians were randomized to receive an educational memorandum alone or combined with feedback regarding their individual prescribing behavior. The memo suggested preferred use of an H2-blocker (cimetidine) that would be less expensive to the HMO. Prescribing was monitored during the 6 months before and after the intervention. The study was undertaken at the primary care practices of a mixed group- and network-model university-affiliated HMO. Thirty group-model (at two academic and four nonacademic sites) and 33 network-model (all in full-time private practice) primary care physicians participated in the study. The analysis utilized weighted and unweighted analysis of covariance of the change in physicians' cimetidine-prescribing rates between the baseline and study periods. A significant response to the intervention was noted among academic and nonacademic group-model HMO physicians, but not among network physicians (adjusted mean absolute prescribing changes of +9.9% and +8.9% versus -2.8%, P = .02). There was no difference in prescribing change based on type of intervention (education versus feedback). The authors conclude that a simple passive educational intervention can be effective at changing group-model HMO physician behavior.", "Asthma continues to be a substantial cause of morbidity in pediatric populations. New strategies are needed to provide cost-effective educational interventions for children with asthma, particularly those in the inner city.\n To assess the effectiveness of a multimedia educational software program about asthma.\n A hospital-based primary care clinic and an affiliated neighborhood health center.\n Randomized, controlled trial.\n Children 3 to 12 years old with physician-diagnosed asthma.\n An interactive educational computer program, Asthma Control, designed to teach children about asthma and its management. Using a graphic display of a child going through simulated daily events, the game emphasizes: 1) monitoring; 2) allergen identification; 3) use of medications; 4) use of health services; and 5) maintenance of normal activity. Control group participants reviewed printed educational materials with a research assistant.\n Acute health care use (emergency department and outpatient) was the primary outcome. Secondary outcome measures included maternal report of asthma symptom severity, child functional status and school absences, satisfaction with care, and parental and child knowledge of asthma.\n A total of 137 families were enrolled in the study (76 intervention, 61 control). Both intervention and control groups showed substantial improvement in all outcomes during the 12-month follow-up period. Aside from improvement in knowledge after use of the computer program, no differences were demonstrated between the 2 groups in primary or secondary outcome measures. Children reported enjoyment of program use.\n This trial of an educational software program found that it did not produce greater improvement than occurred with review of traditional written materials. Because both groups showed substantial improvement over baseline, computer-based education may be more cost-effective. Alternatively, improvements in illness severity over time may overshadow the effects of such interventions. Rigorous comprehensive evaluations such as this are necessary to assess new interventions intended to improve management and outcomes of asthma.", "The Diabetes Education Study was a controlled trial of the effects of physician and patient education. This article describes an educational program for internal medicine residents and its effects on ambulatory diabetes management practices. Forty-five of 86 residents practicing in the general medicine clinic of a university-affiliated city/county hospital were assigned randomly to receive a multifaceted program intended to 1) provide specific care recommendations, 2) teach necessary skills, and 3) make the professional and institutional environment more supportive. During the subsequent 11 months, 323 diabetic patients were interviewed and their records audited for evidence of changes in care. Experimental residents utilized fasting blood glucose determinations more often than controls (i.e., during 40% of visits vs. 31%, p = 0.004). Experimental residents also engaged more frequently in a variety of recommended dietary management recommendations. Isolated differences in monitoring/management of chronic complications also were found (e.g., lipid screening: 70% of experimental residents' patients vs. 58%, p = 0.016). Intensive, multifaceted programs of this nature are concluded to result in improvements in diabetes care, over and above that which is attainable through routine methods of clinical training for residents.", "The effect of clinical guidelines on resource utilization for complex conditions with substantial barriers to clinician behavior change has not been well studied. We report the impact of a multifaceted guideline implementation intervention on primary care clinician utilization of radiologic and specialty services for the care of acute low back pain.\n Physician groups were randomized to receive guideline education and individual feedback, supporting patient education materials, both, or neither. The impact on guideline adherence and resource utilization was evaluated during the 12-month period before and after implementation.\n Fourteen physician groups with 120 primary care physician and associate practitioners from 2 group model HMO practices.\n Guideline implementation utilized an education/audit/feedback model with local peer opinion leaders. The patient education component included written and videotaped materials on the care of low back pain.\n The clinician intervention was associated with an absolute increase in guideline-consistent behavior of 5.4% in the intervention group versus a decline of 2.7% in the control group (P =.04). The patient education intervention produced no significant change in guideline-consistent behavior, but was poorly adopted. Patient characteristics including duration of pain, prior history of low back pain, and number of visits during the illness episode were strong predictors of service utilization and guideline-consistent behavior.\n Implementation of an education and feedback-supported acute low back pain care guideline for primary care clinicians was associated with an increase in guideline-consistent behavior. Patient education materials did not enhance guideline effectiveness. Implementation barriers could limit the utility of this approach in usual care settings.", "To evaluate patient education and resident education strategies to promote advance directives in the outpatient setting, and to assess barriers to implementation.\n Controlled clinical trial.\n The internal medicine residents' practice of an urban, university medical center.\n Medical residents and 250 patients seen at least twice in the 3 months prior to the study.\n We randomized practice days: one to patient education, one to resident education, and three controls. Resident education consisted of a lecture, a videotape of a model advance directives discussion, and videotaping of an actual discussion by each resident, followed by individual review. Patient education consisted of distributing pamphlets in the waiting room and offering all patients an opportunity to discuss advance directives.\n We interviewed 187 of these patients (response rate 75%) and surveyed 62 residents (response rate 70%). After 18 months, there were no significant differences in the number of advance directives in charts among the three groups. Documented advance directives discussions with patients in the resident education group increased from 3% to 17% (p < .001), more than those in the patient education (5%) or control group (10%, p = .04). Residents in the resident education group were more likely to report discussing advance directives than those in the patient education or control groups (p = .05). Lack of time (95%) and lack of continuity (76%) were the most frequently cited barriers. In multivariate logistic regression, nonwhite race and non-U.S. birth were negatively associated with patient interest in advance directives. Patient race and birthplace were not associated with actual discussions of advance directives.\n Even with intensive efforts to educate outpatients and residents about advance directives, important barriers remain, raising questions about how best to promote advance directives among outpatients.", "To assess the effects of a communication skills training program for physicians and patients.\n A randomized experiment to improve physician communication skills was assessed 1 and 6 months after a training intervention; patient training to be active participants was assessed after 1 month. Across three primary medical care settings, 156 physicians treating 2,196 patients were randomly assigned to control group or one of three conditions (physician, patient, or both trained).\n Patient satisfaction and perceptions of choice, decision-making, information, and lifestyle counseling; physicians' satisfaction and stress; and global ratings of the communication process.\n The following significant (p < .05) effects emerged: physician training improved patients' satisfaction with information and overall care; increased willingness to recommend the physician; increased physicians' counseling (as reported by patients) about weight loss, exercise, and quitting smoking and alcohol; increased physician satisfaction with physical exam detail; increased independent ratings of physicians' sensitive, connected communication with their patients, and decreased physician satisfaction with interpersonal aspects of professional life. Patient training improved physicians' satisfaction with data collection; if only physician or patient was trained, physician stress increased and physician satisfaction decreased.\n Implications for improving physician-patient relationship outcomes through communication skills training are discussed.\n PsycINFO Database Record (c) 2008 APA, all rights reserved.", "In the international Drug Education Project, a new educational program for peer groups of doctors was developed and tested to improve the treatment of asthma patients in The Netherlands, Norway, Sweden, and Slovakia. Individualized feedback on prescribing and the underlying decision strategy was presented and discussed within the group of doctors, in relation to existing guidelines. In a parallel, randomized controlled design the effect on competence and actual prescribing was tested. Results were related to national guidelines. In general, the program improved the doctors' attitudes as well as some of their prescribing behavior. The proportion of patients treated with inhaled corticosteroids significantly improved in The Netherlands (effect size 1.27), and the proportion of oral corticosteroid use for exacerbation treatment increased both in The Netherlands and in Norway (effect sizes 1.99 and 0.87, respectively). Overall attitudes of Dutch and Norwegian doctors also improved significantly (effect sizes 1.06 and 0.87, respectively), as did both knowledge (effect size 1.06) and attitudes (effect size 1.49) concerning exacerbation treatment in Slovakia. In Sweden no significant improvements could be measured. Conclusively, improvements in asthma treatment are possible with an educational program based on self-learning in small peer groups, although effects in one health care setting may not occur in another health care setting. Possible explaining factors may be different attitudes to and experiences with guidelines as well as with continuing medical education programs, and differences in the opportunities for change, including prevailing trends in prescribing behavior.", "Management of diabetes is frequently suboptimal in primary care settings, where providers often fail to intensify therapy when glucose levels are high, a problem known as clinical inertia. We asked whether interventions targeting clinical inertia can improve outcomes.\n A controlled trial over a 3-year period was conducted in a municipal hospital primary care clinic in a large academic medical center. We studied all patients (4,138) with type 2 diabetes who were seen in continuity clinics by 345 internal medicine residents and were randomized to be control subjects or to receive one of three interventions. Instead of consultative advice, the interventions were hard copy computerized reminders that provided patient-specific recommendations for management at the time of each patient's visit, individual face-to-face feedback on performance for 5 min every 2 weeks, or both.\n Over an average patient follow-up of 15 months within the intervention site, improvements in and final HbA1c (A1C) with feedback + reminders (deltaA1C 0.6%, final A1C 7.46%) were significantly better than control (deltaA1C 0.2%, final A1C 7.84%, P < 0.02); changes were smaller with feedback only and reminders only (P = NS vs. control). Trends were similar but not significant with systolic blood pressure (sBP) and LDL cholesterol. Multivariable analysis showed that the feedback intervention independently facilitated attainment of American Diabetes Association goals for both A1C and sBP. Over a 2-year period, overall glycemic control improved in the intervention site but did not change in other primary care sites (final A1C 7.5 vs. 8.2%, P < 0.001).\n Feedback on performance aimed at overcoming clinical inertia and given to internal medicine resident primary care providers improves glycemic control. Partnering generalists with diabetes specialists may be important to enhance diabetes management in other primary care settings.", "Home health nurses provided individualized instruction in diabetes self-care within the home environment of 393 diabetic individuals. Each subject was randomly assigned to either the intervention (those receiving home teaching) or control (those not receiving home teaching) group. At 6 mo postenrollment, intervention subjects showed significantly greater self-care knowledge and skills than control subjects, although the actual differences between the two groups in terms of self-care skills were probably too small to have any practical meaning. The primary objective of the study, which was the reduction of the number of preventable diabetes-related hospitalizations (ketoacidosis, ketotic coma, nonketotic coma, insulin reaction, and diabetes out of control), was not achieved; no differences between the groups were noted after 12 mo of follow-up. Similarly, length of hospital stay, foot problems, emergency room and physician visits, and sick days were roughly equivalent in both groups during the follow-up year. These results suggest that, in the absence of concurrent changes in the health-care delivery system and strategies for influencing attitudes toward self-care, education alone is ineffective.", "To determine if written feedback improves the chart documentation and knowledge of physicians doing evaluations for child sexual abuse and to learn what other factors are associated with better documentation and knowledge.\n Randomized, controlled trial.\n A statewide network of physicians performing child abuse evaluations.\n All physicians who performed evaluations for sexual abuse during 1991 to 1992. One hundred forty-seven physicians were randomized to control (n = 75) and intervention (n = 72) groups, 122 (83%) remained at follow-up, and 87 of the 122 (71%) had done evaluations for child sexual abuse.\n Tailored written feedback based on chart reviews and relevant articles were sent to a randomly selected one-half of the physicians during a 3-month period.\n The quality of documentation and physician knowledge before and after the intervention.\n Documentation by chart review of up to five randomly chosen records per physician (preintervention, n = 552; postintervention, n = 259) by reviewers blinded to intervention status and physician knowledge was assessed by survey (78% completion). Change in documentation and knowledge for physicians in the intervention group was not statistically significant compared with the control group. The risk ratio for a mean overall history rating of excellent/good was 0.89 (0.63, 1.25) and for a mean overall physical examination rating of excellent/good was 1.03 (0.73, 1.45). Both groups improved significantly during the time period. The largest improvements in the time period were in documenting the history of where abuse occurred, in the physical examination position, hymenal description, penile findings, and knowing that chlamydia infection should be assessed by culture. A structured medical record, female physicians, and credits in continuing medical education were associated with better documentation.\n Tailored feedback to the physician with directed educational materials did not seem to improve most aspects of documentation and knowledge of child sexual abuse, although notable improvement was seen during the time period studied. This study suggests that chart audits may not be the best use of resources for trying to improve physician behavior; credits in continuing medical education and use of structured records may be more likely to be beneficial.", "This study evaluated the impact of child-focused information provision using a multimedia software package 'All About Nocturnal Enuresis' and written leaflets containing the same information for bedwetting children.\n A stratified cluster randomized controlled trial with data on 270 children collected longitudinally.\n Fifteen school nurse-led community enuresis clinics in Leicestershire, UK.\n The outcome measures were becoming and remaining dry and time to dry, non-attendance and dropout rates. The psychological measures completed by children were the impact of bedwetting and Coopersmith self-esteem scales. Parents completed the maternal tolerance scale.\n No significant intervention effect was found for any of the outcome measures recorded during treatment, at discharge or six-months post discharge.\n Multimedia educational programs and written leaflets are widely used to enable children to learn more about their health-related conditions. However, our result suggests that multimedia is no more effective than traditional materials at effecting health-related behavioural change.", "Patients with inflammatory bowel disease (IBD) suffer physical dysfunction and impaired quality of life (QOL), and need frequent health care. They often lack knowledge about their disease and desire more education. Educational interventions for other chronic diseases have demonstrated reduced health care use and increased knowledge, medication adherence and QOL.\n Sixty-nine participants were randomly assigned to formal IBD education and standard of care (pamphlets and ad hoc physician education) or standard of care alone. Assessment of IBD knowledge and QOL occurred at baseline, immediately posteducation and eight weeks posteducation. Participants documented medication adherence and health care use in diaries. Patient satisfaction was assessed at the end of the study.\n The education group had higher knowledge scores (P=0.000), perceived knowledge ratings (P=0.01) and patient satisfaction (P=0.001). There was a lower rate of medication nonadherence and health care use for the education group, but the differences were not significant. QOL indices did not change. Significant correlations were found for increased health care use in patients with poorer medication adherence (P=0.01) and lower perceived health (P=0.05).\n Formal IBD patient education improves knowledge, perceived knowledge and patient satisfaction. Further study of long-term effects may better demonstrate potential benefits for QOL, medication adherence and health care use.", "A prospective experimental design evaluated the ability of a series of educational and motivational interventions to enhance self-treatment by adult asthmatics and to reduce use of emergency department services for asthma attacks. After treatment for an asthma attack, subjects were randomly assigned to the following sequential interventions: (1) reinforcement by interpersonal similarity at the time of the emergency visit, (2) recepit of positive written appeals, and (3) follow-up telephone reinforcement. The asthmatic nurse educator was generally more effective in achieving short-term reduction of emergency department visits. Although the usefulness of the positive written appeal increased when employed by the asthmatic nurse, there were no substantive independent effects of the written message on emergency department use.", "Despite high prevalence, emotional distress among primary care patients often goes unrecognized during routine medical encounters.\n To explore the effect of communication-skills training on the process and outcome of care associated with patients' emotional distress.\n A randomized, controlled field trial was conducted with 69 primary care physicians and 648 of their patients. Physicians were randomized to a no-training control group or one of two communication-skills training courses designed to help physicians address patients' emotional distress. The two training courses addressed communication through problem-defining skills or emotion-handling skills. All office visits of study physicians were audiotaped until five emotionally distressed and five nondistressed patients were enrolled based on patient response to the General Health Questionnaire. Physicians were also audiotaped interviewing a simulated patient to evaluate clinical proficiency. Telephone monitoring of distressed patients for utilization of medical services and General Health Questionnaire scores was conducted 2 weeks, 3 months, and 6 months after their audiotaped office visits.\n Audiotape analysis of actual and simulated patients showed that trained physicians used significantly more problem-defining and emotion-handling skills than did untrained physicians, without increasing the length of the visit. Trained physicians also reported more psychosocial problems, engaged in more strategies for managing emotional problems with actual patients, and scored higher in clinical proficiency with simulated patients. Patients of trained physicians reported reduction in emotional distress for as long as 6 months.\n Important changes in physicians' communication skills were evident after an 8-hour program. The training improved the process and outcome of care without lengthening the visits.", "Nursing staffs from two long-term care facilities attended a multisession educational program about the care of residents with diabetes (treatment group). A control group consisted of the nursing staffs from two other similar facilities who did not participate in the educational program. Both groups were given a knowledge pretest and posttest. A chart review also was conducted following the educational intervention to determine any changes in the diabetes care provided by the treatment group. Following the educational program, the treatment group had a significant increase in their mean score on the knowledge test compared with the control group. However, a review of the residents' charts revealed no significant increases in specific behaviors related to diabetes care. The findings suggest that, in addition to educational programs, more focused training concerning diabetes care is needed to improve the care of residents with diabetes in long-term care facilities. Implications for diabetes educators are discussed.", "To explore effects of a health risk appraisal for older people (HRA-O) program with reinforcement, we conducted a randomized controlled trial in 21 general practices in Hamburg, Germany.\n Overall, 2,580 older patients of 14 general practitioners trained in reinforcing recommendations related to HRA-O-identified risk factors were randomized into intervention (n = 878) and control (n = 1,702) groups. Patients (n = 746) of seven additional matched general practitioners who did not receive this training served as a comparison group. Patients allocated to the intervention group, and their general practitioners, received computer-tailored written recommendations, and patients were offered the choice between interdisciplinary group sessions (geriatrician, physiotherapist, social worker, and nutritionist) and home visits (nurse).\n Among the intervention group, 580 (66%) persons made use of personal reinforcement (group sessions: 503 [87%], home visits: 77 [13%]). At 1-year follow-up, persons in the intervention group had higher use of preventive services (eg, influenza vaccinations, adjusted odds ratio 1.7; 95% confidence interval 1.4-2.1) and more favorable health behavior (eg, high fruit/fiber intake, odds ratio 2.0; 95% confidence interval 1.6-2.6), as compared with controls. Comparisons between intervention and comparison group data revealed similar effects, suggesting that physician training alone had no effect. Subgroup analyses indicated favorable effects for HRA-O with personal reinforcement, but not for HRA-O without reinforcement.\n HRA-O combined with physician training and personal reinforcement had favorable effects on preventive care use and health behavior." ]	Educational meetings alone or combined with other interventions, can improve professional practice and healthcare outcomes for the patients. The effect is most likely to be small and similar to other types of continuing medical education, such as audit and feedback, and educational outreach visits. Strategies to increase attendance at educational meetings, using mixed interactive and didactic formats, and focusing on outcomes that are likely to be perceived as serious may increase the effectiveness of educational meetings. Educational meetings alone are not likely to be effective for changing complex behaviours.
CD007543	[ "10860187", "10765007", "6341720", "1611136", "8366922", "1563531", "11358679", "19767384", "3136331", "3288533", "1611835", "6381006", "4018423", "7587918", "15839185", "18539916" ]	[ "Long-term results of the Kumamoto Study on optimal diabetes control in type 2 diabetic patients.", "The effects of intensive glycemic control on neuropathy in the VA cooperative study on type II diabetes mellitus (VA CSDM).", "Effect of blood glucose control on peripheral nerve function in diabetic patients.", "Peripheral and autonomic nerve function in 259 diabetic patients with peripheral neuropathy treated with ponalrestat (an aldose reductase inhibitor) or placebo for 18 months. United Kingdom/Scandinavian Ponalrestat Trial.", "The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group.", "A multicentre trial of the aldose-reductase inhibitor tolrestat, in patients with symptomatic diabetic peripheral neuropathy. North European Tolrestat Study Group.", "Lipid modulation in insulin-dependent diabetes mellitus: effect on microvascular outcomes.", "Incremental value of continuous glucose monitoring when starting pump therapy in patients with poorly controlled type 1 diabetes: the RealTrend study.", "Regeneration and repair of myelinated fibers in sural-nerve biopsy specimens from patients with diabetic neuropathy treated with sorbinil.", "Autonomic and somatosensory nerve function after 2 years of continuous subcutaneous insulin infusion in type I diabetes.", "A 12-month randomized controlled study of the aldose reductase inhibitor ponalrestat in patients with chronic symptomatic diabetic neuropathy.", "Continuous subcutaneous insulin infusion (Mill-Hill Infuser) versus multiple injections (Medi-Jector) in the treatment of insulin-dependent diabetes mellitus and the effect of metabolic control on microangiopathy.", "Two-year experience with continuous subcutaneous insulin infusion in relation to retinopathy and neuropathy.", "Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study.", "Proactive case management of high-risk patients with type 2 diabetes mellitus by a clinical pharmacist: a randomized controlled trial.", "Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes." ]	[ "To examine whether intensive glycemic control could decrease the frequency or severity of diabetic microvascular complications, an 8-year prospective study of Japanese patients with type 2 diabetes was performed.\n A total of 110 patients with type 2 diabetes (55 with no retinopathy [the primary prevention cohort] and 55 with simple retinopathy [the secondary intervention cohort]) were randomly assigned to multiple insulin injection therapy (MIT) groups and administered three or more daily insulin injections or assigned to conventional insulin injection therapy (CIT) groups and administered one or two daily intermediate-acting insulin injections. Worsening of microvascular complications was regularly assessed during 8 years. Two or more steps up in the 19 stages of the modified Early Treatment of Diabetic Retinopathy Study classification in retinopathy and one or more stages up among three stages in nephropathy (normoalbuminuria, microalbuminuria, and albuminuria) were defined as worsening of complications.\n In both primary prevention and secondary intervention cohorts, the cumulative percentages of worsening in retinopathy and nephropathy were significantly lower (P < 0.05) in the MIT group than in the CIT group. In neurological tests after 8 years, the MIT group showed significant improvement (P < 0.05) in the median nerve conduction velocities (motor and sensory nerves), whereas the CIT group showed significant deterioration (P < 0.05) in the nerve conduction velocities and vibration threshold. From this study, the glycemic threshold to prevent the onset and progression of diabetic microvascular complications was as follows: HbA1c < 6.5%, fasting blood glucose concentration < 110 mg/dl, and 2-h postprandial blood glucose concentration < 180 mg/dl.\n Intensive glycemic control can delay the onset and progression of the early stages of diabetic microvascular complications in Japanese patients with type 2 diabetes.", "To determine whether a difference in HbA(1c) could be safely sustained between a standard therapy (STD) arm and an intensive therapy (INT) arm, while maintaining HbA(1c) levels in both arms within a range acceptable in community practice. The effects of intensive treatment on various parameters were studied in this feasibility trial. We report here the results of 24 months of INT on peripheral and autonomic neuropathy.A prospective trial was conducted in five medical centers in 153 men of 60 +/- 6 years of age who had a known diagnosis of diabetes for 7.8 +/- 4 years. They were randomly assigned to a standard insulin treatment group (one morning injection per day) or to an intensive therapy group designed to attain near-normal glycemia and a clinically significant separation of glycohemoglobin from the standard arm. A four-step plan was used in the intensive therapy group along with daily self-monitoring of glucose: (1) an evening insulin injection, (2) the same injection adding daytime glipizide, (3) two injections of insulin alone, and (4) multiple daily injections. Peripheral neuropathy was diagnosed clinically by a history and physical examination, and by abnormal autonomic neuropathy Valsalva ratio (VR < 1.2) and RR variation (RRV < 10). An average HbA(1c) separation of 2.07% was achieved with INT, having HbA(1c) at or below 7.3% (p = 0. 001 versus STD). Baseline prevalence of peripheral neuropathy was 53% in STD, and 48% in INT. By 24 months, the prevalence increased to 69% in STD (p = 0.005 versus baseline), and to 64% in INT (p = 0. 008 versus baseline, but no different than STD). Though INT did not reverse all elements of peripheral neuropathy, there was a decreased prevalence of cranial neuropathy (p = 0.053 versus STD) and more frequent preservation of touch sensation in the upper extremities (p = 0.03 versus STD) in INT. At baseline, an abnormal Valsalva ratio and/or RR variation was seen in 38% of STD and 31% of INT. By 24 months in STD, the prevalence rose to 55% (p = 0.0067 versus baseline), and in INT, to 48% (p = 0.012 versus baseline and no different from STD). The prevalence of erectile dysfunction increased from 53% at baseline to 73% at 2 years, p = 0.002 in STD, and from 51% to 73% at 2 years (p = 0.003 versus baseline) and no different from STD. There was no change in the frequency of abnormal gastrointestinal or sweating symptoms. Our conclusion was that 2 years of meticulous glycemic control did not decrease overall prevalence of peripheral or autonomic neuropathy. In fact, the prevalence rose equivalently and significantly in both treatment arms. There was some benefit, however, in decreased frequency of cranial neuropathy and better preservation of touch sensation in INT.", "A prospective, stratified, randomized 3-year clinical trial was conducted on the effect of rigorous versus conventional glucose control on peripheral nerve function in 33 insulin-treated diabetic patients with a duration of diabetes of less than 2 years. The goals for conventional glucose control were the mean of fasting and 80-minute postprandial plasma glucose of 150 mg/dl for non-insulin-dependent diabetes and 200 mg/dl for insulin-dependent diabetes. The goal of rigorous glucose control was an approximation of nondiabetic glucose control. No significant difference in glucose control or peripheral nerve function was observed between the rigorously and the conventionally controlled groups. Eight patients in the conventional-control group spontaneously achieved glucose control in the range that was the objective for the rigorous-control group, and five patients in the rigorous-control group never achieved the desired glucose control. In the remaining 20 patients, with similar baseline glucose control and peripheral nerve function characteristics, observed over a median of 2 years, improved blood glucose control (P less than 0.01) was not associated with any significant improvement in peripheral nerve function. Nevertheless, a significant (P less than 0.05) correlation was found between the degree of abnormal nerve function at entry into the study and change in nerve function during the study. If control of hyperglycemia benefits peripheral nerve function of diabetic patients, its demonstration may require a closer approximation of normoglycemia, a larger difference in glucose control between the two study groups, a longer duration of treatment, and the use of patients with more advanced peripheral nerve function abnormalities than those in this study.", "The potential of the aldose reductase inhibitor ponalrestat (600 mg daily) to ameliorate diabetic neuropathy was evaluated in 259 diabetes mellitus patients with peripheral neuropathy (defined by abnormal vibration perception threshold and abnormal peroneal motor conduction velocity) in a double-blind placebo-controlled clinical trial running for 18 months. Overall, no beneficial effect of ponalrestat on vibration perception thresholds, nerve conduction velocities, and nerve action potential amplitudes was detected. Because vibration perception thresholds and conduction velocities in median, peroneal, and sural nerves did not deteriorate in the placebo group, the potential of ponalrestat to prevent the expected deterioration in peripheral nerve function that occurs with an increased duration of diabetes was not tested. Patients with an abnormal heart rate reaction to standing (abnormal 30:15 ratio; n = 84) on ponalrestat did not deteriorate in this autonomic nerve function test as shown in those on placebo. In conclusion, ponalrestat did not improve peripheral nerve function in diabetes mellitus patients with signs of peripheral neuropathy, although it did ameliorate a deterioration in autonomic nerve function in diabetic patients with signs of autonomic neuropathy.", "Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with insulin-dependent diabetes mellitus (IDDM). We examined whether intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of these complications.\n A total of 1441 patients with IDDM--726 with no retinopathy at base line (the primary-prevention cohort) and 715 with mild retinopathy (the secondary-intervention cohort) were randomly assigned to intensive therapy administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood glucose monitoring or to conventional therapy with one or two daily insulin injections. The patients were followed for a mean of 6.5 years, and the appearance and progression of retinopathy and other complications were assessed regularly.\n In the primary-prevention cohort, intensive therapy reduced the adjusted mean risk for the development of retinopathy by 76 percent (95 percent confidence interval, 62 to 85 percent), as compared with conventional therapy. In the secondary-intervention cohort, intensive therapy slowed the progression of retinopathy by 54 percent (95 percent confidence interval, 39 to 66 percent) and reduced the development of proliferative or severe nonproliferative retinopathy by 47 percent (95 percent confidence interval, 14 to 67 percent). In the two cohorts combined, intensive therapy reduced the occurrence of microalbuminuria (urinary albumin excretion of > or = 40 mg per 24 hours) by 39 percent (95 percent confidence interval, 21 to 52 percent), that of albuminuria (urinary albumin excretion of > or = 300 mg per 24 hours) by 54 percent (95 percent confidence interval 19 to 74 percent), and that of clinical neuropathy by 60 percent (95 percent confidence interval, 38 to 74 percent). The chief adverse event associated with intensive therapy was a two-to-threefold increase in severe hypoglycemia.\n Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM.", "One hundred and ninety patients with symptomatic diabetic peripheral neuropathy took part in a double blind multicentre trial of either placebo or tolrestat 200 mg once daily for 6 months. Painful and paraesthetic symptoms, vibration sensory threshold, and nerve conduction velocity (NCV) were assessed as efficacy end-points during the trial. There was an equally marked improvement of painful symptoms during the trial in the tolrestat and placebo groups. A difference in the improvement of paraesthetic symptoms was found however in favour of the placebo group at 24 weeks (p less than 0.02). The deterioration in mean vibration threshold of the tolrestat group was less than placebo at 24 weeks at all 3 sites measured, and reached significance at the carpal site (p less than 0.05). Significant improvements in median motor NCV and in the mean NCV of the four motor nerves were also seen in tolrestat treated patients at 24 weeks compared to placebo (p less than 0.05). In addition, significant changes in favour of tolrestat were seen when the number of motor nerves per patient with NCV increased during the trial was analysed (p less than 0.001). Concordance analysis of patients with increased mean motor NCV and improvement in painful symptoms demonstrated a positive effect for tolrestat compared to placebo (p less than 0.02). Mild reversible elevations of hepatic transaminases were seen in a few patients treated with tolrestat, with no other significant adverse effects. Tolrestat may therefore be helpful in diabetic peripheral neuropathy, where there is little opportunity for therapeutic intervention apart from effort to achieve normoglycaemic control.", "Although hyperlipidemia is associated with the development of diabetes complications, the effect of lipid reduction on microvascular complications is unknown. We initiated a 2-year, randomized, double-blinded placebo-controlled pilot trial of simvastatin/diet vs. diet alone in Type 1 diabetic patients without overt nephropathy. Thirty-nine patients with LDL cholesterol 100-160 mg/dl, >10 year duration of diabetes and an albumin excretion rate (AER) <200 microg/min were recruited for study. The primary end-point was change in AER. Secondary end-points were change in ankle-brachial index, progression of retinopathy status, change in vibratory threshold, and development of new clinical neuropathy. Nineteen patients were treated with simvastatin and twenty with placebo. However, because of the lowering of drug initiation levels by the American Diabetes Association, the trial was terminated early with 2 subjects reaching 2 years, 17 reaching 18 months, 36 reaching 1 year, and all 6 months. Simvastatin significantly reduced total cholesterol (mean on treatment 173.4 vs. 191.4, P=.020) and LDL cholesterol (mean on treatment 105.0 vs. 127.7, P<.001). Simvastatin therapy was associated with a slower rise in AER compared to placebo, though the result was not statistically significant (median rate of change/month 0.004 vs. 0.029). There was a trend towards slower progression of neuropathy as measured by vibratory threshold (median change at 1 year 0.03 simvastatin vs. 0.94, P=.07). There was no difference in change in ankle-brachial index, clinical neuropathy status, or retinopathy status. In conclusion, treatment with simvastatin may have a beneficial effect on early nephropathy and diabetic neuropathy, justifying a fully powered trial. However, this would be difficult under current treatment guidelines.", "To compare the improvements in glycemic control associated with transitioning to insulin pump therapy in patients using continuous glucose monitoring versus standard blood glucose self-monitoring.\n The RealTrend study was a 6-month, randomized, parallel-group, two-arm, open-label study of 132 adults and children with uncontrolled type 1 diabetes (A1C >or=8%) being treated with multiple daily injections. One group was fitted with the Medtronic MiniMed Paradigm REAL-Time system (PRT group), an insulin pump with integrated continuous subcutaneous glucose monitoring (CGM) capability, with instructions to wear CGM sensors at least 70% of the time. Conventional insulin pump therapy was initiated in the other group (continuous subcutaneous insulin infusion [CSII] group). Outcome measures included A1C and glycemic variability.\n A total of 115 patients completed the study. Between baseline and trial end, A1C improved significantly in both groups (PRT group -0.81 +/- 1.09%, P < 0.001; CSII group -0.57 +/- 0.94%, P < 0.001), with no significant difference between groups. When the 91 patients who were fully protocol-compliant (including CGM sensor wear >or=70% of the time) were considered, A1C improvement was significantly greater in the PRT group (P = 0.004) (PRT group -0.96 +/- 0.93%, P < 0.001; CSII group -0.55 +/- 0.93%, P < 0.001). Hyperglycemia parameters decreased in line with improvements in A1C with no impact on hypoglycemia.\n CGM-enabled insulin pump therapy improves glycemia more than conventional pump therapy during the first 6 months of pump use in patients who wear CGM sensors at least 70% of the time.", "There is reason to believe that diabetic neuropathy may be related to the accumulation of sorbitol in nerve tissue through an aldose reductase pathway from glucose. Short-term treatment with aldose reductase inhibitors improves nerve conduction in subjects with diabetes, but the effects of long-term treatment on the neuropathologic changes of diabetic neuropathy are unknown. To determine whether more prolonged aldose reductase inhibition reverses the underlying lesions that accompany symptomatic diabetic peripheral polyneuropathy, we performed a randomized, placebo-controlled, double-blind trial of the investigational aldose reductase inhibitor sorbinil (250 mg per day). Sural-nerve biopsy specimens obtained at base line and after one year from 16 diabetic patients with neuropathy were analyzed morphometrically in detail and compared with selected electrophysiologic and clinical indexes. In contrast to patients who received placebo, the 10 sorbinil-treated patients had a decrease of 41.8 +/- 8.0 percent in nerve sorbitol content (P less than 0.01) and a 3.8-fold increase in the percentage of regenerating myelinated nerve fibers (P less than 0.001), reflected by a 33 percent increase in the number of myelinated fibers per unit of cross-sectional area of nerve (P = 0.04). They also had quantitative improvement in terms of the degree of paranodal demyelination, segmental demyelination, and myelin wrinkling. The increase in the number of fibers was accompanied by electrophysiologic and clinical evidence of improved nerve function. We conclude that sorbinil, as a metabolic intervention targeted against a specific biochemical consequence of hyperglycemia, can improve the neuropathologic lesions of diabetic neuropathy.", "Autonomic and somatosensory nerve function was studied in 24 insulin-dependent diabetic subjects (aged 29 +/- 7 yrs, diabetes duration 8 +/- 4 yr) randomly allocated to either continuous subcutaneous insulin infusion (CSII; n = 12) or unchanged conventional insulin therapy (CIT; n = 12). Measures of glycemic control and somatosensory and autonomic nerve function were comparable in the two groups at the start. Glycemic control was significantly improved in the CSII group throughout study, whereas it remained unchanged in the CIT group. In the CIT group, vibratory perception threshold (VPT) of the great toe and the medial malleolus deteriorated, as did heart rate variation (HRV) at rest, at deep breathing (.05 less than P less than .06), and at standing. In contrast, CSII patients retained their VPT and HRV. Comparison of nerve function alterations during the 2-yr trial showed better preservation in CSII than in CIT patients of VPT in the great toe (0.8 +/- 1.7 vs. -1.4 +/- 1.9 V, P less than .01) and the medial malleolus (1.5 +/- 2.9 vs. -1.4 +/- 1.8 V, P less than .05) and of HRV at rest (10 +/- 24 vs. -13 +/- 22 ms, P less than .05) and at standing (-0.01 +/- 0.13 vs. -0.15 +/- 0.16 ms, P less than .05). We conclude that intensified glycemic control can favorably influence parasympathetic and somatosensory nerve function in insulin-dependent diabetes mellitus.", "The effects of the aldose reductase inhibitor ponalrestat (600 mg day-1) on sensory, electrophysiological, and autonomic function were examined in 50 patients with chronic symptomatic, distal symmetrical diabetic neuropathy in a 52-week randomized, double-blind, parallel-group, placebo-controlled, single-centre study. In an endeavour to identify patients with a degree of neuropathy potentially amenable to pharmacological intervention, a minimum conduction velocity of 30 m s-1 was set for the peroneal motor nerve. At 52 weeks, no significant differences were observed between the ponalrestat and placebo groups in motor (ulnar, median, and peroneal) or sensory (ulnar and radial) nerve conduction velocities, vibration perception thresholds, adjectival symptom scores or tests of autonomic function (mean electrocardiographic R-R interval variability on deep breathing and orthostatic blood pressure response). Ponalrestat was clinically well tolerated and had no significant effect on glycaemic control. The lack of beneficial effects of ponalrestat may in part reflect the advanced stage of the neuropathic process in patients with established symptomatic disease, and the poor reproducibility of current neurophysiological techniques. Firmer knowledge of clinico-pathological correlates allied to improved non-invasive neurophysiological measurement techniques should facilitate the selection of patients for future therapeutic trials in diabetic neuropathy.", "The present study was designed to compare continuous subcutaneous insulin infusion (CSII) using the Mill-Hill Infuser (Muirhead Medical Products Ltd., London, England) with multiple injections (MI) using the Medi-Jector (Derata Corporation, Minneapolis, Minnesota) in the treatment of insulin-dependent diabetes mellitus (IDDM), and to assess the effect of glucose control on diabetes complications. Twelve diabetic subjects were treated 3 mo with CSII and 3 mo with MI (bedtime ultralente and premeal boluses of regular insulin) in a randomized fashion. Prestudy preprandial/postprandial glucose levels were 147-215 mg/dl and improved to 108-138 mg/dl during CSII, and to 115-139 mg/dl during MI with glycosylated hemoglobin of 12.9%, 9.1%, and 8.7%, respectively. This improved glucose control with either CSII or MI was associated with an increase in sural nerve conductivity from 42.9 to 45 m/s and a decrease in proteinuria from 1.9 to 0.5 g/24 h. The 24-h insulin dose consisted of 45 U before the study, 44 U during CSII, and 56 U during MI. After the study, seven patients opted to continue with the Mill-Hill Infuser, and five with the Medi-Jector. We conclude the following: (1) treatment with both the Mill-Hill Infuser and the Medi-Jector was well accepted by the patients and resulted in similar improvement in measured blood glucose and glycosylated hemoglobin; (2) this improved metabolic control was associated with an increased nerve conductivity and a decreased protein excretion; and (3) MI required 20% more insulin than CSII to achieve similar glycemic control.", "Thirty patients with insulin-dependent diabetes mellitus (IDDM) who had advanced background retinopathy were randomized to unchanged conventional treatment (UCT) or to continuous subcutaneous insulin infusion (CSII). They were followed prospectively for 2 yr. The mean blood glucose and hemoglobin A1C (HbA1C) were significantly lower in the CSII group than in the UCT group. The mean blood glucose and HbA1C did not change from the first to the second year in either of the treatment groups in spite of less frequent home-monitoring of blood glucose and less frequent outpatient visits during the second year. Four patients in the CSII group and five in the UCT group developed proliferative retinopathy. However, a marginally significant trend was found toward more frequent improvement of retinal morphology in the CSII group (47%) than in the UCT group (13%). Beat-to-beat variation was found to deteriorate significantly with UCT compared with a nonsignificant improvement with CSII therapy. Vibration sense was unchanged in both treatment groups. It is concluded that near-normal blood glucose levels can be maintained with CSII therapy in spite of less frequent home-monitoring of blood glucose and outpatient visits. Furthermore, established background retinopathy may progress to proliferative retinopathy in spite of 2 yr of near-normal blood glucose levels. However, a marginally significant trend toward more frequent improvement of retinal morphology was found among CSII-treated patients compared with conventionally treated patients. Large-scale, prospective, randomized studies are needed to confirm these results.", "To examine whether intensive glycemic control could decrease the frequency or severity of diabetic microvascular complications, we performed a prospective study of Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM) treated with multiple insulin injection treatment. A total of 110 patients with NIDDM was randomly assigned to multiple insulin injection treatment group (MIT group) or to conventional insulin injection treatment group (CIT group). Fifty-five NIDDM patients who showed no retinopathy and urinary albumin excretions < 30 mg/24 h at the baseline were evaluated in the primary-prevention cohort, and the other 55 NIDDM patients who showed simple retinopathy and urinary albumin excretions < 300 mg/24 h were evaluated in the secondary-intervention cohort. The appearance and the progression of retinopathy, nephropathy and neuropathy were evaluated every 6 months over a 6-year period. The worsening of complications in this study was defined as an increase of 2 or more steps in the 19 stages of the modified ETDRS interim scale for retinopathy and an increase of one or more steps in 3 stages (normoalbuminuria, microalbuminuria and albuminuria) for nephropathy. The cumulative percentages of the development and the progression in retinopathy after 6 years were 7.7% for the MIT group and 32.0% for the CIT group in the primary-prevention cohort (P = 0.039), and 19.2% for MIT group and 44.0% for CIT group in the secondary-intervention cohort (P = 0.049). The cumulative percentages of the development and the progression in nephropathy after 6 years were 7.7% for the MIT group and 28.0% for the CIT group in the primary-prevention cohort (P = 0.032), and 11.5% and 32.0%, respectively, for the MIT and CIT groups in the secondary-intervention cohort (P = 0.044). In neurological tests after 6 years, MIT group showed significant improvement in the nerve conduction velocities, while the CIT group showed significant deterioration in the median nerve conduction velocities and vibration threshold. Although both postural hypotension and the coefficient of variation of R-R interval tended to improve in the MIT group, they deteriorated in the CIT group. In conclusion, intensive glycemic control by multiple insulin injection therapy can delay the onset and the progression of diabetic retinopathy, nephropathy and neuropathy in Japanese patients with NIDDM. From this study, the glycemic threshold to prevent the onset and the progression of diabetic microangiopathy is indicated as follows; HbA1c < 6.5%, FBG < 110 mg/dl, and 2-h post-prandial blood glucose concentration < 180 mg/dl.", "To evaluate the effect of case management by a clinical pharmacist on glycemic control and preventive measures in patients with type 2 diabetes mellitus.\n Randomized controlled trial in a university-affiliated primary care internal medicine clinic.\n We recruited 80 patients with poorly controlled type 2 diabetes mellitus. A clinical pharmacist provided evaluation and modification of pharmacotherapy, self-management diabetes education, and reinforcement of diabetes complications screening processes through clinic visits and telephone follow-up. The main clinical outcome was hemoglobin A1C (HbA1C) level; process measures included HbA1C and low-density lipoprotein measurement, retinal examination, urine microalbumin testing (or use of angiotensin-converting enzyme inhibitors), and monofilament screening for diabetic neuropathy.\n Patients in the intervention and control groups were similar in age, sex, mean HbA1C levels (10.1% and 10.2%, respectively; P = .65), and current treatment regimens at baseline. Patients who received case management by the clinical pharmacist achieved greater reduction in HbA1C levels than those in the control group (2.1% vs 0.9%, P = .03). Three of the 5 process measures were conducted more frequently in the intervention group than the control group, including low-density lipoprotein measurement (100.0% vs 85.7%, P = .02), retinal examination (97.3% vs 74.3%), and monofilament foot screening (92.3% vs 62.9%).\n Proactive diabetes case management by a pharmacist substantially improved glycemic control and diabetes process-of-care measures. This approach, integrated with and based in the primary care setting, was an effective and efficient approach to improving care, especially for those with poor glycemic control at baseline.", "In patients with type 2 diabetes, the effects of intensive glucose control on vascular outcomes remain uncertain.\n We randomly assigned 11,140 patients with type 2 diabetes to undergo either standard glucose control or intensive glucose control, defined as the use of gliclazide (modified release) plus other drugs as required to achieve a glycated hemoglobin value of 6.5% or less. Primary end points were composites of major macrovascular events (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) and major microvascular events (new or worsening nephropathy or retinopathy), assessed both jointly and separately.\n After a median of 5 years of follow-up, the mean glycated hemoglobin level was lower in the intensive-control group (6.5%) than in the standard-control group (7.3%). Intensive control reduced the incidence of combined major macrovascular and microvascular events (18.1%, vs. 20.0% with standard control; hazard ratio, 0.90; 95% confidence interval [CI], 0.82 to 0.98; P=0.01), as well as that of major microvascular events (9.4% vs. 10.9%; hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), primarily because of a reduction in the incidence of nephropathy (4.1% vs. 5.2%; hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006), with no significant effect on retinopathy (P=0.50). There were no significant effects of the type of glucose control on major macrovascular events (hazard ratio with intensive control, 0.94; 95% CI, 0.84 to 1.06; P=0.32), death from cardiovascular causes (hazard ratio with intensive control, 0.88; 95% CI, 0.74 to 1.04; P=0.12), or death from any cause (hazard ratio with intensive control, 0.93; 95% CI, 0.83 to 1.06; P=0.28). Severe hypoglycemia, although uncommon, was more common in the intensive-control group (2.7%, vs. 1.5% in the standard-control group; hazard ratio, 1.86; 95% CI, 1.42 to 2.40; P<0.001).\n A strategy of intensive glucose control, involving gliclazide (modified release) and other drugs as required, that lowered the glycated hemoglobin value to 6.5% yielded a 10% relative reduction in the combined outcome of major macrovascular and microvascular events, primarily as a consequence of a 21% relative reduction in nephropathy. (ClinicalTrials.gov number, NCT00145925.)\n 2008 Massachusetts Medical Society" ]	According to high-quality evidence, enhanced glucose control significantly prevents the development of clinical neuropathy and reduces nerve conduction and vibration threshold abnormalities in type 1 diabetes mellitus. In type 2 diabetes mellitus, enhanced glucose control reduces the incidence of clinical neuropathy, although this was not formally statistically significant (P = 0.06). However, enhanced glucose control does significantly reduce nerve conduction and vibration threshold abnormalities. Importantly, enhanced glucose control significantly increases the risk of severe hypoglycemic episodes, which needs to be taken into account when evaluating its risk/benefit ratio.
CD001078	[ "7567201", "2651597" ]	[ "Does continuous positive airway pressure (CPAP) during weaning from intermittent mandatory ventilation in very low birth weight infants have risks or benefits? A controlled trial.", "Successful extubation of newborn infants without preextubation trial of continuous positive airway pressure." ]	[ "The purpose of this study was to evaluate three ventilator weaning strategies and to evaluate whether the use of continuous positive airway pressure (CPAP) via a nasopharyngeal or endotracheal tube would increase the likelihood of extubation failure in very low birth weight (VLBW) infants.\n We studied prospectively 87 preterm infants (mean +/- SD; birth weight: 1078 +/- 188 g; gestational age: 28.8 +/- 2.2 weeks) who were in the process of being weaned from intermittent mandatory ventilation (IMV). Infants were assigned by systematic sampling to one of the following three treatment groups: (1) direct extubation from IMV (D.EXT) (n = 30); (2) preextubation endotracheal CPAP (ET-CPAP) for 12-24 hr (n = 28); or (3) postextubation nasopharyngeal CPAP (NP-CPAP) for 12-24 hr (n = 29). Failure was defined as the need for resumption of mechanical ventilation within 72 hr of extubation due to frequent or severe apnea and/or respiratory failure (pH < 7.25, PaCO2 > 60 mm Hg, and/or requirement for oxygen FiO2 > 60%).\n There were no significant differences in failure rates among the three procedures. Failures were 2/30 (7%) in D.EXT; 4/28 (14%) in ET-CPAP; and 7/29 (24%) in the NP-CPAP. There were also no differences in FiO2, PaO2, and respiratory rates before and after discontinuation of IMV among the three groups. PaCO2 values were slightly higher in the NP-CPAP group 12-24 hr after weaning from IMV.\n We were unable to demonstrate a clear difference in extubation outcome by use of CPAP administered via an endotracheal or nasopharyngeal tube when compared to direct extubation from low-rate IMV in VLBW infants.", "Sixty newborn infants who had been mechanically ventilated through 3.0- or 3.5-mm endotracheal tubes were studied to examine the necessity of a preextubation trial of continuous positive airway pressure (CPAP). Thirty randomly assigned study infants were directly extubated from intermittent mandatory ventilation rates of six per minute; 30 randomly assigned control infants were extubated after a six-hour trial of continuous positive airway pressure of 3 cm H2O. Changes in respiratory rate, in PCO2, and in PO2/FIO2 were similar. All 30 study infants tolerated direct extubation without significant apnea or respiratory acidosis. Two study and eight control infants developed apnea during six hours after intermittent mandatory ventilation was discontinued (chi 2 = 4.3, P less than .05). Five control and no study infants had apneic episodes greater than or equal to 0.5 per hour (chi 2 = 5.5, P less than .02). The results of this study suggest that newborn infants may tolerate direct extubation from low intermittent mandatory ventilation rates without a preextubation trial of CPAP. A preextubation trial of CPAP appears to be unnecessary and may cause more frequent apnea in newborn infants if used for more than several hours." ]	Preterm infants no longer requiring endotracheal intubation and IPPV should be directly extubated without a trial of ETT CPAP.
CD008727	[ "11443157", "12825213", "16291357", "15181060", "17828747", "10891816", "15192618" ]	[ "Evaluation of the hypothalamic-pituitary-adrenal axis in children with leukemia before and after 6 weeks of high-dose glucocorticoid therapy.", "Impaired adrenal function after glucocorticoid therapy in children with acute lymphoblastic leukemia.", "Clinical impact of corticosteroid-induced adrenal suppression during treatment for acute lymphoblastic leukemia in children: a prospective observational study using the low-dose adrenocorticotropin test.", "Early adrenocortical recovery after glucocorticoid therapy in children with leukemia.", "Adrenal axis function after high-dose steroid therapy for childhood acute lymphoblastic leukemia.", "Time course of recovery of adrenal function in children treated for leukemia.", "Suppression of adrenal function in children with acute lymphoblastic leukemia following induction therapy with corticosteroid and other cytotoxic agents." ]	[ "Among the adverse effects arising from chronic high-dose glucocorticoid treatment, adrenal insufficiency secondary to suppression of the hypothalamic-pituitary-adrenal (HPA) axis is a cause for concern. Glucocorticoid-induced adrenal suppression is related to the duration of therapy, type of steroid used and dosage, and schedule of glucocorticoid administration. To evaluate the suppression and recovery time of the HPA axis in children with acute leukemia, we performed the ovine CRH (oCRH) stimulation test in 15 patients, who were given high doses of dexamethasone as part of their induction chemotherapy for 42 days. The oCRH tests were performed before, and 7 and 14 days after, discontinuation of the glucocorticoid. The ACTH levels were not significantly different among the 3 tests. The cortisol levels, however, were significantly (albeit mildly) lower, both basally and after oCRH, 1 and 2 weeks post treatment than before therapy. Six patients had cortisol values that remained suppressed 2 weeks after discontinuation of therapy. One of these patients had manifestations of mild adrenal insufficiency, 6-8 days after discontinuation of therapy, but required no glucocorticoid coverage. We conclude that up to 2 weeks after discontinuation of 6 weeks of high-dose dexamethasone administration, the HPA axis of patients with acute leukemia is mildly suppressed but infrequently associated with clinical manifestations of adrenal insufficiency. This may indicate that major stress, when concurrent with glucocorticoid treatment, may prevent clinically significant adrenal suppression.", "Glucocorticoids are commonly used in the treatment of childhood acute lymphoblastic leukemia (ALL). The purpose of this study was to assess the incidence of adrenal insufficiency and the time for children with ALL to recover after treatment with the glucorticoids prednisolone or dexamethasone.\n Seventeen children, 2-15 years, with ALL were studied after receiving prednisolone (60 mg/m(2)/day, n = 10) for 5 weeks during remission induction therapy or dexamethasone (10 mg/m(2)/day, n = 7) for 3 weeks during reinduction therapy. Both drugs were tapered over 9 days. The adrenal function was assessed by an ACTH stimulation test within 2 weeks after discontinuing glucocorticoid therapy. In case of adrenal insufficiency, the ACTH test was repeated at 3-5 weeks interval, and patients were put on hydrocortisone substitution therapy.\n Three out of ten patients had a normal adrenal function within the first 2 weeks after prednisolone therapy. Another three patients recovered within 7 weeks, whereas the remaining four patients still showed adrenal insufficiency at the end of follow-up after 2.5-4 months. For dexamethasone, two out of seven patients showed a normal adrenal function within the first 2 weeks. Of the remaining patients, two recovered within 7 weeks, whereas three patients still had a demonstrated adrenal insufficiency at the end of follow-up after 4-8 months.\n Adrenal insufficiency occurs and may persist for several months in children with ALL after treatment with high doses of prednisolone or dexamethasone.\n Copyright 2003 Wiley-Liss, Inc.", "To investigate how frequently adrenal function fails to recover after corticosteroid therapy in children with acute lymphoblastic leukemia and to explore the clinical impact of slow adrenal recovery without steroid substitution.\n Low-dose (1 microg) adrenocorticotropic hormone tests were performed before and after steroid courses and during infectious episodes in 24 children. Test results were not available during the study.\n All 13 patients tested before treatment had normal adrenal responses. Adrenal suppression was found in 8 (47%) of 17 patients 5 days after discontinuation of a 5-week induction course of prednisolone and in 1 (20%) of 5 patients 7 days after a 3-week intensification course of dexamethasone, both courses being tapered over 9 days, as well as in all 13 patients tested 2 days after a 1-week prednisolone course. Clinically significant manifestations of adrenal suppression were noted in 3 (12%) patients. Of 204 scheduled tests, 131 were performed.\n High-dose glucocorticoid therapy may cause adrenal suppression lasting more than 1 week in children with acute lymphoblastic leukemia, even after tapering the dose. We suggest steroid replacement during stress episodes within 1 to 2 weeks after discontinuation and thereafter testing adrenal function selectively in accordance with symptoms.", "The duration of glucocorticoid-induced inhibition that occurs in the hypothalamic-pituitary-adrenal (HPA) axis after discontinuation of treatment is controversial. The main objective of this prospective study was to evaluate the inhibition of the HPA axis by dexamethasone in children and adolescents with acute lymphoid leukemia. Thirty-five patients (median age of 6.9 yr) were evaluated. A stimulus test with ovine CRH (1 microg/kg) was performed before the introduction of dexamethasone (6 mg/m2.d for 28 d), in the 8th and 28th days of glucocorticoid therapy, and 48 h and 1 month after discontinuation of glucocorticoid therapy. Suppression of the basal secretion as well as the maximum concentration of ACTH occurred during glucocorticoid therapy (P < 0.01). The pituitary function before the introduction of dexamethasone was similar to the one seen 48 h and 1 month after withdrawing it. Suppression of the adrenal function was detected during glucocorticoid therapy, which persisted for 48 h after the steroid was removed from treatment (P < 0.01). One month after ceasing the administration of the glucocorticoid, the adrenal function was similar to that before glucocorticoid therapy. According to these results, a clinical and laboratory follow-up of the HPA axis in the month after the cessation of dexamethasone therapy is suggested to determine glucocorticoid replacement.", "A 4-week course of high-dose glucocorticoids may cause prolonged adrenal suppression even after a 9-day tapering phase. In this study, adrenal function and signs and symptoms of adrenal insufficiency were prospectively assessed in children with acute lymphoblastic leukemia (ALL) after induction treatment including high-dose prednisone (PDN) or dexamethasone (DXM).\n Sixty-four children with ALL, treated according to the AIEOP ALL 2000 Study protocol, underwent low dose ACTH (LD-ACTH) stimulation 24 hr after the last tapered steroid dose. In those with impaired cortisol response, additional LD ACTH tests were performed every 1-2 weeks until cortisol levels normalized. Signs and symptoms of adrenal insufficiency were recorded during the observation period.\n All patients had normal basal cortisol values at diagnosis. Twenty-four hours after last glucocorticoid dose, morning cortisol was reduced in 40/64 (62.5%) patients. LD-ACTH testing showed adrenal suppression in 52/64 (81.5%) patients. At the following ACTH test 7-14 days later, morning cortisol values were reduced in 8/52 (15.4%) patients and response to the test was impaired in 12/52 (23%). Adrenal function completely recovered in all patients within 10 weeks. No difference was found between patients treated with PDN or DXM. Almost 35% of children with impaired cortisol values at the first test developed signs or symptoms of adrenal insufficiency. One child developed a severe adrenal crisis during adrenal suppression.\n High-dose glucocorticoid therapy in ALL children may cause prolonged adrenal suppression and related clinical symptoms. Laboratory monitoring of cortisol levels and steroid coverage during stress episodes may be indicated.\n (c) 2007 Wiley-Liss, Inc.", "Many protocols for treating children with early B-cell lineage acute lymphoblastic leukemia use 28 consecutive days of high-dose glucocorticoids during induction therapy. We prospectively studied the effects of this therapy on adrenal function.\n Ten children with early B-cell lineage acute lymphoblastic leukemia were evaluated by cosyntropin (corticotropin (1-24)) stimulation testing before initiation of dexamethasone therapy and every 4 weeks thereafter until adrenal function returned to normal.\n All 10 patients had normal adrenal function before dexamethasone treatment and insufficient adrenal responses 24 hours after completing therapy. Each child felt ill for 2 to 4 weeks after completing therapy. Although 7 patients recovered normal adrenal function after 4 weeks, 3 patients did not have normal adrenal function until 8 weeks after discontinuing therapy. Statistically significant differences in both basal and corticotropin-stimulated cortisol levels were noted when comparing tests performed at baseline, 24 hours after completing therapy, and 4 weeks after completing therapy.\n High-dose dexamethasone therapy, a standard treatment for early B-cell acute lymphoblastic leukemia, can cause adrenal insufficiency lasting more than 4 weeks after cessation of treatment. This problem might be avoided by tapering doses of glucocorticoids and providing supplemental glucocorticoids during periods of increased stress.", "To evaluate adrenal function in children with acute lymphoblastic leukemia (ALL) after induction therapy with corticosteroid and other cytotoxic agents. Study design Children with ALL (N=24) were treated with prednisolone (40 mg/m(2) per day) for 28 days during the induction phase followed by 1 week of oral dexamethasone every 4 weeks. A low-dose (1 microg) adrenocorticotropin (ACTH) test was performed 2 weeks after discontinuation of prednisolone; it was repeated 2 weeks later and then every 4 weeks in patients with adrenal suppression until normal response was achieved.\n Adrenal suppression was found in 46% of patients at 2 weeks after discontinuation of prednisolone; it persisted in 38%, 29%, and 13% of patients through 4 weeks, 8 weeks, and 20 weeks, respectively. Adrenal suppression appeared to last significantly longer in children aged >or=5 years than in children aged <5 years. Four children developed febrile neutropenia; all belonged to the adrenal suppressed group and were unable to mount an adequate adrenal response to the stress.\n About 50% of children with ALL developed adrenal suppression 2 weeks after a 4-week induction therapy with prednisolone. The suppression could persist through 20 weeks and may hinder an adequate adrenal response during acute febrile illness." ]	Based on the available evidence, we conclude that adrenal insufficiency commonly occurs in the first days after cessation of glucocorticoid therapy for childhood ALL, but the exact duration is unclear. Since no data on the level of the hypothalamus and the pituitary were available we cannot make any conclusions regarding those outcomes. Clinicians should consider prescribing glucocorticoid replacement therapy during periods of serious stress in the first weeks after cessation of glucocorticoid therapy for childhood ALL, to reduce the risk of life-threatening complications. However, more high-quality research is needed for evidence-based guidelines for glucocorticoid replacement therapy. Special attention should be paid to patients receiving fluconazole therapy, and perhaps similar antifungal drugs, as this may prolong the duration of adrenal insufficiency.
CD007448	[ "3276864", "3901372" ]	[ "A randomized, controlled trial of parenteral clindamycin in neonatal necrotizing enterocolitis.", "Treatment of intra-abdominal infections is appropriate with single-agent or combination antibiotic therapy." ]	[ "For an assessment of the efficacy of clindamycin in preventing bowel necrosis (intestinal gangrene or perforation), 42 premature infants with radiographically confirmed necrotizing enterocolitis (NEC) (pneumatosis, intraportal gas, or both) were randomly assigned to receive parenterally either ampicillin and gentamicin (control group, n = 22) or ampicillin, gentamicin, and clindamycin (n = 20), 20 mg/kg/d at 8-hour intervals for 10 to 14 days. Infants who had received antibiotics for greater than 24 hours before randomization and those developing intestinal gangrene or perforation less than 12 hours after randomization were excluded. Intestinal gangrene or perforation developed in four infants in the control group and six in the clindamycin group. Four in each group died of NEC. In the control group, one of 18 survivors developed a late stricture requiring surgical resection, whereas six of 15 survivors in the clindamycin group developed such strictures (P = 0.022). Routine inclusion of clindamycin in medical treatment of NEC does not reduce the frequency of intestinal gangrene or perforation and may be associated with an increase in late stricture formation.", "In a prospective, randomized, single-blind trial, we studied 112 adults with intra-abdominal infections and compared antibiotic therapy with cefoxitin plus placebo to therapy with tobramycin plus clindamycin. Seventy-five percent of patients receiving tobramycin-clindamycin and 71% of those receiving cefoxitin-placebo had either shock, bacteremia, malnutrition, alcoholism, rapidly or ultimately fatal underlying disease, infection originating from the distal small bowel or colon, or had had failed therapy before treatment (\"high-risk\" group). One third of the patients in both groups grew bacteria in the initial culture resistant to the antibiotic regimen used. Ten patients receiving cefoxitin-placebo (17%) and 11 receiving tobramycin-clindamycin (21%) had recurrence of infection or died of infection (clinical failures). Nineteen failures occurred in high-risk patients (p less than 0.05) and 17 were in patients that had antibiotic-resistant bacteria in the initial culture (p less than 0.01). Adverse effects were rare and remitted after antibiotics were stopped. Our results suggest that both cefoxitin and tobramycin-clindamycin are appropriate antibiotic regimens to treat intra-abdominal infections. Clinical failure is more common in high-risk patients and when antibiotic-resistant organisms are isolated from initial cultures." ]	There was insufficient evidence to recommend a particular antibiotic regimen for the treatment of NEC. There were concerns about adverse effects following the usage of clindamycin, related to the development of strictures. To address this issue a large randomised controlled trial needs to be performed.
CD008079	[ "21321292", "15284112", "21231927", "20194844", "16946304" ]	[ "Chemoimmunotherapy with fludarabine and rituximab produces extended overall survival and progression-free survival in chronic lymphocytic leukemia: long-term follow-up of CALGB study 9712.", "The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group.", "A randomized phase II trial of fludarabine, cyclophosphamide and mitoxantrone (FCM) with or without rituximab in previously treated chronic lymphocytic leukaemia.", "Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia.", "Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG)." ]	[ "The addition of rituximab to fludarabine-based regimens in chronic lymphocytic leukemia (CLL) has been shown to produce high response rates with extended remissions. The long-term follow-up of these regimens with respect to progression, survival, risk of secondary leukemia, and impact of genomic risk factors has been limited.\n We report the long-term follow-up of the chemoimmunotherapy trial CALGB 9712 from the Cancer and Leukemia Group B, for which treatment regimen was previously reported, to examine end points of progression-free survival (PFS), overall survival (OS), impact of genomic features, and risk of therapy-related myeloid neoplasm (t-MN).\n A total of 104 patients were enrolled on this study and now have a median follow-up of 117 months (range, 66 to 131 months). The median OS was 85 months, and 71% of patients were alive at 5 years. The median PFS was 42 months, and 27% were progression free at 5 years. An estimated 13% remained free of progression at almost 10 years of follow-up. Multivariable models of PFS and OS showed that immunoglobulin heavy chain variable region mutational status was significant for both, whereas cytogenetic abnormalities were significant only for OS. No patient developed t-MN before relapse.\n Long-term follow-up of CALGB 9712 demonstrates extended OS and PFS with fludarabine plus rituximab. Patients treated with fludarabine plus rituximab administered concurrently or sequentially have a low risk of t-MN. These long-term data support fludarabine plus rituximab as one acceptable first-line treatment for symptomatic patients with CLL.", "In follicular lymphoma (FL) and mantle cell lymphoma (MCL) the monoclonal antibody rituximab may improve the prognosis when combined with chemotherapy. This was investigated in a prospective randomized study in patients with relapsed disease. A total of 147 patients were randomized to receive 4 courses of chemotherapy with 25 mg/m(2) fludarabine on days 1 to 3, 200 mg/m(2) cyclophosphamide on days 1 to 3, and 8 mg/m(2) mitoxantrone on day 1 (FCM), alone or combined with rituximab (375 mg/m(2); R-FCM). Of 128 evaluable patients, 62 were randomized for FCM and 66 for R-FCM. R-FCM revealed an overall response rate of 79% (33% complete remission [CR], 45% partial remission [PR]) as compared with 58% for FCM alone (13% CR, 45% PR; P = .01), with similar results in a subgroup analysis of FL (94% vs 70%) and MCL (58% vs 46%). In the total group, the R-FCM arm was significantly superior concerning progression-free survival (PFS; P = .0381) and overall survival (OS; P = .0030). In FL PFS was significantly longer in the R-FCM arm (P = .0139) whereas in MCL a significantly longer OS was observed (P = .0042). There were no differences in clinically relevant side effects in both study arms. Hence, the addition of rituximab to FCM chemotherapy significantly improves the outcome of relapsed or refractory FL and MCL.", "Combination fludarabine (F), cyclophosphamide (C) and rituximab (R) is the standard front-line therapy in chronic lymphocytic leukaemia (CLL), but appropriate treatment of relapsed/refractory CLL is less clear. Combined FC and mitoxantrone (M) has been reported to be effective in a single arm study, and rituximab when added to chemotherapy in CLL is synergistic. A randomized, two-stage, Phase II trial of FCM and FCM-R was conducted in relapsed CLL. The primary endpoint was response rate 2 months after therapy, assessed according to the 2008 International Workshop CLL criteria. In addition, minimal residual disease (MRD) in the marrow was studied 2 months after therapy, with MRD negativity defined as <0·01% CLL cells. Fifty-two patients were entered, 26 in each arm. The overall response rates to FCM and FCM-R were 58% and 65% respectively. Combined complete response (CR) and CR with incomplete marrow recovery [CR(i)] was 15% (95% confidence interval [CI]:4-35%) for FCM and 42% (95%CI:23-63%) for FCM-R, with eight patients achieving MRD negativity (3 FCM; 5 FCM-R). The toxicity of both regimens was acceptable. In conclusion, the addition of rituximab to FCM improves the response rates in relapsed CLL, resulting in more complete remissions and without additional safety concerns. Efficacy and safety should be fully tested in a randomized Phase III trial.\n © 2011 Blackwell Publishing Ltd.", "Rituximab, a monoclonal antibody that targets the CD20 cell surface antigen, has clinical activity in patients with non-Hodgkin's lymphoma and other B-lymphocyte disorders when administered alone or in combination with chemotherapy. Promising results have previously been reported in nonrandomized studies in patients with chronic lymphocytic leukemia (CLL). This trial was designed to compare chemoimmunotherapy with chemotherapy alone in patients with previously treated CLL.\n This international, multicenter, randomized trial compared six cycles of rituximab plus fludarabine and cyclophosphamide (R-FC) with six cycles of fludarabine and cyclophosphamide alone (FC) in patients with previously treated CLL. A total of 552 patients with Binet stage A (1%), B (59%), or C (31%) disease entered the study and were randomly assigned to receive R-FC (n = 276) or FC (n = 276).\n After a median follow-up time of 25 months, rituximab significantly improved progression-free survival in patients with previously treated CLL (hazard ratio = 0.65; P < .001; median, 30.6 months for R-FC v 20.6 months for FC). Event-free survival, response rate, complete response rate, duration of response, and time to new CLL treatment or death were also significantly improved. Although the rates of adverse events, grade 3 or 4 events, and serious adverse events were slightly higher in the R-FC arm, R-FC was generally well tolerated, with no new safety findings and no detrimental effect on quality of life.\n R-FC significantly improved the outcome of patients with previously treated CLL.", "In follicular lymphoma (FL) and mantle cell lymphoma (MCL) the monoclonal antibody rituximab (R) improves the prognosis when combined with chemotherapy. The present study investigated R-maintenance after R-chemotherapy. Patients with recurring or refractory FL and MCL were randomized to 4 courses of fludarabine, cyclophosphamide, and mitoxantrone (FCM) alone or combined with R (R-FCM). Responding patients underwent a second randomization for R-maintenance comprising 2 further courses of 4-times-weekly doses of R after 3 and 9 months. The first randomization was stopped after 147 patients, when R-FCM revealed a significantly better outcome. All subsequent patients received R-FCM. Of the 176 patients who are currently evaluable (as of October 2005), 138 received R-FCM for remission induction. Response duration was significantly prolonged by R-maintenance after R-FCM, with the median not being reached in this evaluation versus an estimated median of 16 months (P = .001). This beneficial effect was also observed when analyzing FL (P = .035) and MCL (P = .049) separately. Hence, R-maintenance is effective after salvage with R-chemotherapy and significantly prolongs response duration in patients with recurring or refractory FL or MCL." ]	This meta-analysis showed that patients receiving chemotherapy plus rituximab benefit in terms of OS as well as PFS compared to those with chemotherapy alone. Therefore, it supports the recommendation of rituximab in combination with FluC as an option for the first-line treatment as well as for the people with relapsed or refractory CLL. The available evidence regarding the other assessed comparisons was not sufficient to deduct final conclusions.
CD008143	[ "18539916", "9742976", "9742977", "19396424", "19636533", "1308130", "19142552", "19092145", "19387173", "15154945", "19092238", "21865944", "9786807", "20594588", "18701019", "17434094", "17310047", "11529585" ]	[ "Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.", "Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group.", "Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group.", "Glycaemic impact of patient-led use of sensor-guided pump therapy in type 1 diabetes: a randomised controlled trial.", "A prospective randomised multi-centre controlled trial on tight glucose control by intensive insulin therapy in adult intensive care units: the Glucontrol study.", "Glycemic control and complications in type II diabetes. Design of a feasibility trial. VA CS Group (CSDM)", "Intensive perioperative glucose control does not improve outcomes of patients submitted to open-heart surgery: a randomized controlled trial.", "Glucose control and vascular complications in veterans with type 2 diabetes.", "Continuous perioperative insulin infusion decreases major cardiovascular events in patients undergoing vascular surgery: a prospective, randomized trial.", "Improving glycaemic control of patients with Type 2 diabetes in a primary care setting: a French application of the Staged Diabetes Management programme.", "Pragmatic management of hyperglycaemia in acute ischaemic stroke: safety and feasibility of intensive intravenous insulin treatment.", "Effects of aggressive versus moderate glycemic control on clinical outcomes in diabetic coronary artery bypass graft patients.", "Nurse case management to improve glycemic control in diabetic patients in a health maintenance organization. A randomized, controlled trial.", "Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial.", "Effect of short term intensive multitherapy on carotid intima-media thickness in patients with newly diagnosed type 2 diabetes mellitus.", "Glucose-potassium-insulin infusions in the management of post-stroke hyperglycaemia: the UK Glucose Insulin in Stroke Trial (GIST-UK).", "Intensive intraoperative insulin therapy versus conventional glucose management during cardiac surgery: a randomized trial.", "Effects of improved glycaemic control on endothelial function in patients with type 2 diabetes." ]	[ "In patients with type 2 diabetes, the effects of intensive glucose control on vascular outcomes remain uncertain.\n We randomly assigned 11,140 patients with type 2 diabetes to undergo either standard glucose control or intensive glucose control, defined as the use of gliclazide (modified release) plus other drugs as required to achieve a glycated hemoglobin value of 6.5% or less. Primary end points were composites of major macrovascular events (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) and major microvascular events (new or worsening nephropathy or retinopathy), assessed both jointly and separately.\n After a median of 5 years of follow-up, the mean glycated hemoglobin level was lower in the intensive-control group (6.5%) than in the standard-control group (7.3%). Intensive control reduced the incidence of combined major macrovascular and microvascular events (18.1%, vs. 20.0% with standard control; hazard ratio, 0.90; 95% confidence interval [CI], 0.82 to 0.98; P=0.01), as well as that of major microvascular events (9.4% vs. 10.9%; hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), primarily because of a reduction in the incidence of nephropathy (4.1% vs. 5.2%; hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006), with no significant effect on retinopathy (P=0.50). There were no significant effects of the type of glucose control on major macrovascular events (hazard ratio with intensive control, 0.94; 95% CI, 0.84 to 1.06; P=0.32), death from cardiovascular causes (hazard ratio with intensive control, 0.88; 95% CI, 0.74 to 1.04; P=0.12), or death from any cause (hazard ratio with intensive control, 0.93; 95% CI, 0.83 to 1.06; P=0.28). Severe hypoglycemia, although uncommon, was more common in the intensive-control group (2.7%, vs. 1.5% in the standard-control group; hazard ratio, 1.86; 95% CI, 1.42 to 2.40; P<0.001).\n A strategy of intensive glucose control, involving gliclazide (modified release) and other drugs as required, that lowered the glycated hemoglobin value to 6.5% yielded a 10% relative reduction in the combined outcome of major macrovascular and microvascular events, primarily as a consequence of a 21% relative reduction in nephropathy. (ClinicalTrials.gov number, NCT00145925.)\n 2008 Massachusetts Medical Society", "Improved blood-glucose control decreases the progression of diabetic microvascular disease, but the effect on macrovascular complications is unknown. There is concern that sulphonylureas may increase cardiovascular mortality in patients with type 2 diabetes and that high insulin concentrations may enhance atheroma formation. We compared the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a randomised controlled trial.\n 3867 newly diagnosed patients with type 2 diabetes, median age 54 years (IQR 48-60 years), who after 3 months' diet treatment had a mean of two fasting plasma glucose (FPG) concentrations of 6.1-15.0 mmol/L were randomly assigned intensive policy with a sulphonylurea (chlorpropamide, glibenclamide, or glipizide) or with insulin, or conventional policy with diet. The aim in the intensive group was FPG less than 6 mmol/L. In the conventional group, the aim was the best achievable FPG with diet alone; drugs were added only if there were hyperglycaemic symptoms or FPG greater than 15 mmol/L. Three aggregate endpoints were used to assess differences between conventional and intensive treatment: any diabetes-related endpoint (sudden death, death from hyperglycaemia or hypoglycaemia, fatal or non-fatal myocardial infarction, angina, heart failure, stroke, renal failure, amputation [of at least one digit], vitreous haemorrhage, retinopathy requiring photocoagulation, blindness in one eye, or cataract extraction); diabetes-related death (death from myocardial infarction, stroke, peripheral vascular disease, renal disease, hyperglycaemia or hypoglycaemia, and sudden death); all-cause mortality. Single clinical endpoints and surrogate subclinical endpoints were also assessed. All analyses were by intention to treat and frequency of hypoglycaemia was also analysed by actual therapy.\n Over 10 years, haemoglobin A1c (HbA1c) was 7.0% (6.2-8.2) in the intensive group compared with 7.9% (6.9-8.8) in the conventional group--an 11% reduction. There was no difference in HbA1c among agents in the intensive group. Compared with the conventional group, the risk in the intensive group was 12% lower (95% CI 1-21, p=0.029) for any diabetes-related endpoint; 10% lower (-11 to 27, p=0.34) for any diabetes-related death; and 6% lower (-10 to 20, p=0.44) for all-cause mortality. Most of the risk reduction in the any diabetes-related aggregate endpoint was due to a 25% risk reduction (7-40, p=0.0099) in microvascular endpoints, including the need for retinal photocoagulation. There was no difference for any of the three aggregate endpoints between the three intensive agents (chlorpropamide, glibenclamide, or insulin). Patients in the intensive group had more hypoglycaemic episodes than those in the conventional group on both types of analysis (both p<0.0001). The rates of major hypoglycaemic episodes per year were 0.7% with conventional treatment, 1.0% with chlorpropamide, 1.4% with glibenclamide, and 1.8% with insulin. Weight gain was significantly higher in the intensive group (mean 2.9 kg) than in the conventional group (p<0.001), and patients assigned insulin had a greater gain in weight (4.0 kg) than those assigned chlorpropamide (2.6 kg) or glibenclamide (1.7 kg).\n Intensive blood-glucose control by either sulphonylureas or insulin substantially decreases the risk of microvascular complications, but not macrovascular disease, in patients with type 2 diabetes.(ABSTRACT TRUNCATED)", "In patients with type 2 diabetes, intensive blood-glucose control with insulin or sulphonylurea therapy decreases progression of microvascular disease and may also reduce the risk of heart attacks. This study investigated whether intensive glucose control with metformin has any specific advantage or disadvantage.\n Of 4075 patients recruited to UKPDS in 15 centres, 1704 overweight (>120% ideal bodyweight) patients with newly diagnosed type 2 diabetes, mean age 53 years, had raised fasting plasma glucose (FPG; 6.1-15.0 mmol/L) without hyperglycaemic symptoms after 3 months' initial diet. 753 were included in a randomised controlled trial, median duration 10.7 years, of conventional policy, primarily with diet alone (n=411) versus intensive blood-glucose control policy with metformin, aiming for FPG below 6 mmol/L (n=342). A secondary analysis compared the 342 patients allocated metformin with 951 overweight patients allocated intensive blood-glucose control with chlorpropamide (n=265), glibenclamide (n=277), or insulin (n=409). The primary outcome measures were aggregates of any diabetes-related clinical endpoint, diabetes-related death, and all-cause mortality. In a supplementary randomised controlled trial, 537 non-overweight and overweight patients, mean age 59 years, who were already on maximum sulphonylurea therapy but had raised FPG (6.1-15.0 mmol/L) were allocated continuing sulphonylurea therapy alone (n=269) or addition of metformin (n=268).\n Median glycated haemoglobin (HbA1c) was 7.4% in the metformin group compared with 8.0% in the conventional group. Patients allocated metformin, compared with the conventional group, had risk reductions of 32% (95% CI 13-47, p=0.002) for any diabetes-related endpoint, 42% for diabetes-related death (9-63, p=0.017), and 36% for all-cause mortality (9-55, p=0.011). Among patients allocated intensive blood-glucose control, metformin showed a greater effect than chlorpropamide, glibenclamide, or insulin for any diabetes-related endpoint (p=0.0034), all-cause mortality (p=0.021), and stroke (p=0.032). Early addition of metformin in sulphonylurea-treated patients was associated with an increased risk of diabetes-related death (96% increased risk [95% CI 2-275], p=0.039) compared with continued sulphonylurea alone. A combined analysis of the main and supplementary studies showed fewer metformin-allocated patients having diabetes-related endpoints (risk reduction 19% [2-33], p=0.033). Epidemiological assessment of the possible association of death from diabetes-related causes with the concurrent therapy of diabetes in 4416 patients did not show an increased risk in diabetes-related death in patients treated with a combination of sulphonylurea and metformin (risk reduction 5% [-33 to 32], p=0.78).\n Since intensive glucose control with metformin appears to decrease the risk of diabetes-related endpoints in overweight diabetic patients, and is associated with less weight gain and fewer hypoglycaemic attacks than are insulin and sulphonylureas, it may be the first-line pharmacological therapy of choice in these patients.", "The objective of this study was to assess the impact of patient-led sensor-guided pump management on glycaemic control, and compare the effect with that of standard insulin pump therapy.\n An open multicentre parallel randomised controlled trial was conducted at five tertiary diabetes centres. Participants aged 13.0-40.0 years with well-controlled type 1 diabetes were randomised 1:1 to either study group for 3 months. Randomisation was carried out using a central computer-generated schedule. Participants in the intervention group used sensor-guided pump management; no instructive guidelines in interpreting real-time data were provided ('patient-led' use). Participants in the control group continued their original insulin pump regimen. Continuous glucose monitoring (CGM) and HbA(1c) level were used to assess outcomes. The primary outcome was the difference in the proportion of time in the target glycaemic range during the 3 month study period (derived from CGM, target range 4-10 mmol/l). Secondary outcomes were difference in HbA(1c), time in hypoglycaemic (< or =3.9 mmol/l) and hyperglycaemic (> or =10.1 mmol/l) ranges and glycaemic variability.\n Sixty-two participants were recruited and randomised; 5/31 and 2/31 withdrew from intervention and control groups, respectively, leaving 26/31 and 29/31 for the intention-to-treat analyses. When adjusted for baseline values, the mean end-of-study HbA(1c) was 0.43% lower in the intervention group compared with the control group (95% CI 0.19 to 0.75%; p = 0.009). No difference was observed in CGM-derived time in target (measured difference 1.72; 95% CI -5.37 to 8.81), hypoglycaemic (0.54; 95% CI -3.48 to 4.55) or hyperglycaemic (-2.18; 95% CI -10.0 to 5.69) range or in glycaemic variability (-0.29; 95% CI -0.34 to 0.28). Within the intervention group, HbA(1c) was 0.51% lower in participants with sensor use > or =70% compared with participants with sensor use <70% (95% CI -0.98 to -0.04, p = 0.04). Five episodes of device malfunction occurred.\n Individuals established on insulin pump therapy can employ sensor-guided pump management to improve glycaemic control. An apparent dose-dependent effect of sensor usage was noted; however, frequent use of this technology (> or =70%) was not universally acceptable.\n ACTRN12606000049572", "An optimal target for glucose control in ICU patients remains unclear. This prospective randomized controlled trial compared the effects on ICU mortality of intensive insulin therapy (IIT) with an intermediate glucose control.\n Adult patients admitted to the 21 participating medico-surgical ICUs were randomized to group 1 (target BG 7.8-10.0 mmol/L) or to group 2 (target BG 4.4-6.1 mmol/L).\n While the required sample size was 1,750 per group, the trial was stopped early due to a high rate of unintended protocol violations. From 1,101 admissions, the outcomes of 542 patients assigned to group 1 and 536 of group 2 were analysed. The groups were well balanced. BG levels averaged in group 1 8.0 mmol/L (IQR 7.1-9.0) (median of all values) and 7.7 mmol/L (IQR 6.7-8.8) (median of morning BG) versus 6.5 mmol/L (IQR 6.0-7.2) and 6.1 mmol/L (IQR 5.5-6.8) for group 2 (p < 0.0001 for both comparisons). The percentage of patients treated with insulin averaged 66.2 and 96.3%, respectively. Proportion of time spent in target BG was similar, averaging 39.5% and 45.1% (median (IQR) 34.3 (18.5-50.0) and 39.3 (26.2-53.6)%) in the groups 1 and 2, respectively. The rate of hypoglycaemia was higher in the group 2 (8.7%) than in group 1 (2.7%, p < 0.0001). ICU mortality was similar in the two groups (15.3 vs. 17.2%).\n In this prematurely stopped and therefore underpowered study, there was a lack of clinical benefit of intensive insulin therapy (target 4.4-6.1 mmol/L), associated with an increased incidence of hypoglycaemia, as compared to a 7.8-10.0 mmol/L target. (ClinicalTrials.gov # NCT00107601, EUDRA-CT Number: 200400391440).", "To determine, after 1 yr of follow-up in type II diabetes patients, whether a statistically and clinically significant difference can be achieved in HbA1c between a standard therapy group and an intensively treated group, while maintaining HbA1c levels in both groups within ranges acceptable in regular community practice. Secondary objectives include assessment of patient adherence to protocol, side effects, and accuracy of data collection.\n This is a prospective, randomized, controlled VA CS conducted with 151 patients at five VAMCs. Patients are males, age 40-69 yr, treated at entry with a maximum dose of sulfonylurea or with insulin, exhibiting an HbA1c level > 3 SDs above the normal mean (5.05 + 3 x 0.50 = > 6.55%). Standard control is achieved with insulin and intensive control with a step-up regimen including insulin alone or insulin/glipizide combinations. Education and management of cardiovascular risk factors are handled similarly in both groups. Primary macrovascular end points are nonfatal myocardial infarction, congestive heart failure, stroke, amputation, and cardiovascular death. Primary microvascular end points are appearance and progression of retinopathy, documented by centrally read seven-field-stereo fundus photographs. Other measured indicators include resting and ambulatory ECGs, ventricular function (MUGA scan), serum lipid and apolipoprotein levels, plasma fibrinogen, nonsymptomatic peripheral vasculopathy, neuroautonomic status by heart-beat variation on Valsalva maneuver, and microalbuminuria.\n This study may be the basis for a long-term trial, involving 1400 patients, to assess the long-term effects of metabolic control on macro- and microvascular end points.", "The objective of this study was to investigate the relationship between different target levels of glucose and the clinical outcomes of patients undergoing cardiac surgery with cardiopulmonary bypass.\n We designed a prospective study in a university hospital where 109 consecutive patients were enrolled during a six-month period. All patients were scheduled for open-heart surgery requiring cardiopulmonary bypass. Patients were randomly allocated into two groups. One group consisted of 55 patients and had a target glucose level of 80-130 mg/dl, while the other contained 54 patients and had a target glucose level of 160-200 mg/dl. These parameters were controlled during surgery and for 36 hours after surgery in the intensive care unit. Primary outcomes were clinical outcomes, including time of mechanical ventilation, length of stay in the intensive care unit, infection, hypoglycemia, renal or neurological dysfunction, blood transfusion and length of stay in the hospital. The secondary outcome was a combined end-point (mortality at 30 days, infection or length of stay in the intensive care unit of more than 3 days). A p-value of <0.05 was considered significant.\n The anthropometric and clinical characteristics of the patients from each group were similar, except for weight and body mass index. The mean glucose level during the protocol period was 126.69 mg/dl in the treated group and 168.21 mg/dl in the control group (p<0.0016). There were no differences between groups regarding clinical outcomes, including the duration of mechanical ventilation, length of stay in the intensive care unit, blood transfusion, postoperative infection, hypoglycemic event, neurological dysfunction or 30-day mortality (p>0.05).\n In 109 patients undergoing cardiac surgery with cardiopulmonary bypass, both protocols of glycemic control in an intraoperative setting and in the intensive care unit were found to be safe, easily achieved and not to differentially affect clinical outcomes.", "The effects of intensive glucose control on cardiovascular events in patients with long-standing type 2 diabetes mellitus remain uncertain.\n We randomly assigned 1791 military veterans (mean age, 60.4 years) who had a suboptimal response to therapy for type 2 diabetes to receive either intensive or standard glucose control. Other cardiovascular risk factors were treated uniformly. The mean number of years since the diagnosis of diabetes was 11.5, and 40% of the patients had already had a cardiovascular event. The goal in the intensive-therapy group was an absolute reduction of 1.5 percentage points in the glycated hemoglobin level, as compared with the standard-therapy group. The primary outcome was the time from randomization to the first occurrence of a major cardiovascular event, a composite of myocardial infarction, stroke, death from cardiovascular causes, congestive heart failure, surgery for vascular disease, inoperable coronary disease, and amputation for ischemic gangrene.\n The median follow-up was 5.6 years. Median glycated hemoglobin levels were 8.4% in the standard-therapy group and 6.9% in the intensive-therapy group. The primary outcome occurred in 264 patients in the standard-therapy group and 235 patients in the intensive-therapy group (hazard ratio in the intensive-therapy group, 0.88; 95% confidence interval [CI], 0.74 to 1.05; P=0.14). There was no significant difference between the two groups in any component of the primary outcome or in the rate of death from any cause (hazard ratio, 1.07; 95% CI, 0.81 to 1.42; P=0.62). No differences between the two groups were observed for microvascular complications. The rates of adverse events, predominantly hypoglycemia, were 17.6% in the standard-therapy group and 24.1% in the intensive-therapy group.\n Intensive glucose control in patients with poorly controlled type 2 diabetes had no significant effect on the rates of major cardiovascular events, death, or microvascular complications with the exception of progression of albuminuria (P = 0.01) [added]. (ClinicalTrials.gov number, NCT00032487.)\n 2009 Massachusetts Medical Society", "A growing body of evidence suggests that hyperglycemia is an independent predictor of increased cardiovascular risk. Aggressive glycemic control in the intensive care decreases mortality. The benefit of glycemic control in noncardiac surgery is unknown.\n In a single-center, prospective, unblinded, active-control study, 236 patients were randomly assigned to continuous insulin infusion (target glucose 100-150 mg/dl) or to a standard intermittent insulin bolus (treat glucose > 150 mg/dl) in patients undergoing peripheral vascular bypass, abdominal aortic aneurysm repair, or below- or above-knee amputation. The treatments began at the start of surgery and continued for 48 h. The primary endpoint was a composite of all-cause death, myocardial infarction, and acute congestive heart failure. The secondary endpoints were blood glucose concentrations, rates of hypoglycemia (< 60 mg/dl) and hyperglycemia (> 150 mg/dl), graft failure or reintervention, wound infection, acute renal insufficiency, and duration of stay.\n The groups were well balanced for baseline characteristics, except for older age in the intervention group. There was a significant reduction in primary endpoint (3.5%) in the intervention group compared with the control group (12.3%) (relative risk, 0.29; 95% confidence interval, 0.10-0.83; P = 0.013). The secondary endpoints were similar. Hypoglycemia occurred in 8.8% of the intervention group compared with 4.1% of the control group (P = 0.14). Multivariate analysis demonstrated that continuous insulin infusion was a negative independent predictor (odds ratio, 0.28; 95% confidence interval, 0.09-0.87; P = 0.027), whereas previous coronary artery disease was a positive predictor of adverse events.\n Continuous insulin infusion reduces perioperative myocardial infarction after vascular surgery.", "To assess the impact of a French adaptation of the Staged Diabetes Management (SDM) programme on glycaemic control of people with Type 2 diabetes in primary care. Secondary endpoints were blood pressure, blood lipids, healthcare costs and quality of life.\n Prospective, randomized controlled study, of 1 years' duration. General practitioners (GPs) were recruited in four separate districts of a French region. They enrolled consecutive patients with Type 2 diabetes. GPs in the intervention group were educated in the SDM programme. GPs in the control group were asked to provide usual care. Healthcare costs were collected by medical departments of the Health Insurance systems. Quality of life was assessed with the Duke Health Profile.\n Three hundred and forty patients enrolled by 57 GPs completed the study, 192 in the intervention group and 148 in the control group. Patients in the intervention group were managed more adequately in accordance with the guidelines (P < 0.05 for nine out of 10 items). HbA(1c) decreased by 0.31% in the intervention group and increased by 0.56% in the control group, resulting in a difference of 0.87% by the end of the study (P = 0.001). Blood pressure and blood lipids did not differ between groups. Occurrence of major complications was low and identical in both groups. Incremental costs during the study in the intervention group were 35 euros per patient per month, and this was not significantly different in comparison with the control group. Quality of life was not affected by the intervention.\n Educating GPs in the French adaptation of the SDM programme improves glycaemic control in a primary care setting, without significantly increasing healthcare costs.", "In patients with acute ischaemic stroke, hyperglycaemia has been retrospectively associated with negative outcome. There is an ongoing discussion as to which treatment algorithm, if any, provides the most effective prospective intervention. Here we test the safety and feasibility of an intravenous insulin-only infusion protocol designed for pragmatic routine clinical use.\n 40 ischaemic stroke patients with onset <24 h ago, admitted to our stroke unit, were randomized either to the study regimen (50 IU insulin in 50 ml 0.9% saline solution applied intravenously via a perfusor pump), with the aim of reaching and maintaining blood glucose levels between 4.44 mmol/l (80 mg/dl) and 6.11 mmol/l (110 mg/dl), or were treated with insulin subcutaneously if concentrations were above 11.10 mmol/l (200 mg/dl). Treatment was continued for 5 days. Primary outcome was the number of hypoglycaemic (<3.33 mmol/l; <60 mg/dl) and severe hyperglycaemic (>16.65 mmol/l; >300 mg/dl) events.\n Hypoglycaemic events were significantly more common in patients treated intensively (total n = 25; incidence rate ratio, IRR = 5.3; 95% CI = 1.2-22.4; p < 0.05). Symptomatic events were rare (total n = 5). Severe hyperglycaemia was associated with conventional treatment (IRR = 4.9; 95% CI = 1.5-15.9; p < 0.05). Though those treated intensively attained near-normoglycaemic levels quicker and had significantly lower blood glucose levels over the study period (6.49 +/- 2.19 mmol/l vs. 8.01 +/- 3.06 mmol/l; 95% CI = -1.78 to -1.28, p < 0.0005), treatment imposes considerable strain on both patients and caregivers.\n The intensive intravenous insulin infusion protocol effectively lowers blood glucose levels with an increased risk of manageable hypoglycaemic events. However, a highly motivated and trained staff seems essential, limiting feasibility outside of specialty care settings.\n Copyright (c) 2008 S. Karger AG, Basel.", "This study sought to determine whether aggressive glycemic control (90-120 mg/dL) would result in more optimal clinical outcomes and less morbidity than moderate glycemic control (120-180 mg/dL) in diabetic patients undergoing coronary artery bypass graft (CABG) surgery.\n Maintaining serum glucose levels between 120 and 180 mg/dL with continuous insulin infusions decreases morbidity in diabetic patients undergoing CABG surgery. Studies in surgical patients requiring prolonged ventilation suggest that aggressive glycemic control (<120 mg/dL) may improve survival; however, its effect in diabetic CABG patients is unknown.\n Eighty-two diabetic patients undergoing CABG were prospectively randomized to aggressive glycemic control (90-120 mg/dL) or moderate glycemic control (120-180 mg/dL) using continuous intravenous insulin solutions (100 units regular insulin in 100 mL: normal saline) beginning at the induction of anesthesia and continuing for 18 hours after CABG. Primary end points were the incidence of major adverse events (major adverse events = 30-day mortality, myocardial infarction, neurologic events, deep sternal infections, and atrial fibrillation), the level of serum glucose, and the incidence of hypoglycemic events.\n There were no differences in the incidence of major adverse events between the groups (17 moderate vs 15 aggressive; P = 0.91). Patients with aggressive control had a lower mean glucose at the end of 18 hours of insulin infusion (135 ± 12 mg/dL moderate vs 103 ± 17 mg/dL aggressive; P < 0.0001). Patients with aggressive control had a higher incidence of hypoglycemic events (4 vs 30; P < 0.0001).\n In diabetic patients undergoing CABG surgery, aggressive glycemic control increases the incidence of hypoglycemic events and does not result in any significant improvement in clinical outcomes that can be achieved with moderate control. Clinical Trials.gov (ID #NCT00460499).", "Control of hyperglycemia delays or prevents complications of diabetes, but many persons with diabetes do not achieve optimal control.\n To compare diabetes control in patients receiving nurse case management and patients receiving usual care.\n Randomized, controlled trial.\n Primary care clinics in a group-model health maintenance organization (HMO).\n 17 patients with type 1 diabetes mellitus and 121 patients with type 2 diabetes mellitus.\n The nurse case manager followed written management algorithms under the direction of a family physician and an endocrinologist. Changes in therapy were communicated to primary care physicians. All patients received ongoing care through their primary care physicians.\n The primary outcome, hemoglobin A1c (HbA1c) value, was measured at baseline and at 12 months. Fasting blood glucose levels, medication type and dose, body weight, blood pressure, lipid levels, patient-perceived health status, episodes of severe hypoglycemia, and emergency department and hospital admissions were also assessed.\n 72% of patients completed follow-up. Patients in the nurse case management group had mean decreases of 1.7 percentage points in HbA1c values and 43 mg/dL (2.38 mmol/L) in fasting glucose levels; patients in the usual care group had decreases of 0.6 percentage points in HbA1c values and 15 mg/dL (0.83 mmol/L) in fasting glucose levels (P < 0.01). Self-reported health status improved in the nurse case management group (P = 0.02). The nurse case management intervention was not associated with statistically significant changes in medication type or dose, body weight, blood pressure, or lipids or with adverse events.\n A nurse case manager with considerable management responsibility can, in association with primary care physicians and an endocrinologist, help improve glycemic control in diabetic patients in a group-model HMO.", "Hyperglycaemia is associated with increased risk of cardiovascular complications in people with type 2 diabetes. We investigated whether reduction of blood glucose concentration decreases the rate of microvascular complications in people with type 2 diabetes.\n ACCORD was a parallel-group, randomised trial done in 77 clinical sites in North America. People with diabetes, high HbA(1c) concentrations (>7.5%), and cardiovascular disease (or >or=2 cardiovascular risk factors) were randomly assigned by central randomisation to intensive (target haemoglobin A(1c) [HbA(1c)] of <6.0%) or standard (7.0-7.9%) glycaemic therapy. In this analysis, the prespecified composite outcomes were: dialysis or renal transplantation, high serum creatinine (>291.7 micromol/L), or retinal photocoagulation or vitrectomy (first composite outcome); or peripheral neuropathy plus the first composite outcome (second composite outcome). 13 prespecified secondary measures of kidney, eye, and peripheral nerve function were also assessed. Investigators and participants were aware of treatment group assignment. Analysis was done for all patients who were assessed for microvascular outcomes, on the basis of treatment assignment, irrespective of treatments received or compliance to therapies. ACCORD is registered with ClinicalTrials.gov, number NCT00000620.\n 10 251 patients were randomly assigned, 5128 to the intensive glycaemia control group and 5123 to standard group. Intensive therapy was stopped before study end because of higher mortality in that group, and patients were transitioned to standard therapy. At transition, the first composite outcome was recorded in 443 of 5107 patients in the intensive group versus 444 of 5108 in the standard group (HR 1.00, 95% CI 0.88-1.14; p=1.00), and the second composite outcome was noted in 1591 of 5107 versus 1659 of 5108 (0.96, 0.89-1.02; p=0.19). Results were similar at study end (first composite outcome 556 of 5119 vs 586 of 5115 [HR 0.95, 95% CI 0.85-1.07, p=0.42]; and second 1956 of 5119 vs 2046 of 5115, respectively [0.95, 0.89-1.01, p=0.12]). Intensive therapy did not reduce the risk of advanced measures of microvascular outcomes, but delayed the onset of albuminuria and some measures of eye complications and neuropathy. Seven secondary measures at study end favoured intensive therapy (p<0.05).\n Microvascular benefits of intensive therapy should be weighed against the increase in total and cardiovascular disease-related mortality, increased weight gain, and high risk for severe hypoglycaemia.\n US National Institutes of Health; National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Aging; National Eye Institute; Centers for Disease Control and Prevention; and General Clinical Research Centers.\n Copyright 2010 Elsevier Ltd. All rights reserved.", "Controlling plasma glucose levels, blood pressure and lipid levels is proven to reduce the risk of vascular complications in patients with type 2 diabetes mellitus. This has prompted intensive multitherapy targeted at several macrovascular risk factors. Carotid intima-media thickness (cIMT) is a reliable measure of early atherosclerosis. We sought to determine whether a 6-month intensive mutiltherapy program resulted in better goal attainment than usual care and its effect on the development of cIMT among patients with newly diagnosed type 2 diabetes mellitus.\n The study randomly assigned 220 patients with newly diagnosed type 2 diabetes mellitus to intensive or traditional therapy groups. The clinical parameters, such as fasting plasma glucose, total cholesterol, triglyceride, blood pressure, body weight and insulin were assessed at the baseline and after the 6-month therapy. cIMT of the patients was also obtained.\n The average levels of fasting plasma glucose, hemoglobin A1c, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the intensive group were significantly lower than those in the control group at the end of 6-month treatment. By 6 months, a higher proportion of patients in the intensive therapy group than in the control group attained goals for fasting plasma glucose (FPG), TC, LDL-C and hemoglobin A1c. With intensive multherapy the level of carotid intima-media thickness in the intensive therapy group was lower than that in the control group ((0.88 +/- 0.26) mm vs (0.96 +/- 0.22) mm, P < 0.01).\n The evidence from this clinical trial demonstrates that intensive glucose, lipid and blood pressure control in patients with newly diagnosed type 2 diabetes is associated with diabetic macrovascular benefits. Intensive multitherapy allows more patients to achieve aims of control and may reduce macrovascular complications and delay disease progression.", "Hyperglycaemia after acute stroke is a common finding that has been associated with an increased risk of death. We sought to determine whether treatment with glucose-potassium-insulin (GKI) infusions to maintain euglycaemia immediately after the acute event reduces death at 90 days.\n Patients presenting within 24 h of stroke onset and with admission plasma glucose concentration between 6.0-17.0 mmol/L were randomly assigned to receive variable-dose-insulin GKI (intervention) or saline (control) as a continuous intravenous infusion for 24 h. The purpose of GKI infusion was to maintain capillary glucose at 4-7 mmol/L, with no glucose intervention in the control group. The primary outcome was death at 90 days, and the secondary endpoint was avoidance of death or severe disability at 90 days. Additional planned analyses were done to determine any differences in residual disability or neurological and functional recovery. The trial was powered to detect a mortality difference of 6% (sample size 2355), with 83% power, at the 5% two-sided significance level. This study is registered as an International Standard Randomised Controlled Trial (number ISRCTN 31118803)\n The trial was stopped due to slow enrolment after 933 patients were recruited. For the intention-to-treat data, there was no significant reduction in mortality at 90 days (GKI vs control: odds ratio 1.14, 95% CI 0.86-1.51, p=0.37). There were no significant differences for secondary outcomes. In the GKI group, overall mean plasma glucose and mean systolic blood pressure were significantly lower than in the control group (mean difference in glucose 0.57 mmol/L, p<0.001; mean difference in blood pressure 9.0 mmHg, p<0.0001).\n GKI infusions significantly reduced plasma glucose concentrations and blood pressure. Treatment within the trial protocol was not associated with significant clinical benefit, although the study was underpowered and alternative results cannot be excluded.", "It is not known whether rigorous intraoperative glycemic control reduces death and morbidity in cardiac surgery patients.\n To compare outcomes of intensive insulin therapy during cardiac surgery with those of conventional intraoperative glucose management.\n A randomized, open-label, controlled trial with blinded end point assessment.\n Tertiary care center.\n Adults with and without diabetes who were undergoing on-pump cardiac surgery.\n The primary outcome was a composite of death, sternal infections, prolonged ventilation, cardiac arrhythmias, stroke, and renal failure within 30 days after surgery. Secondary outcome measures were length of stay in the intensive care unit and hospital.\n Patients were randomly assigned to receive continuous insulin infusion to maintain intraoperative glucose levels between 4.4 (80 mg/dL) and 5.6 mmol/L (100 mg/dL) (n = 199) or conventional treatment (n = 201). Patients in the conventional treatment group were not given insulin during surgery unless glucose levels were greater than 11.1 mmol/L (>200 mg/dL). Both groups were treated with insulin infusion to maintain normoglycemia after surgery.\n Mean glucose concentrations were statistically significantly lower in the intensive treatment group at the end of surgery (6.3 mmol/L [SD, 1.6] [114 mg/dL {SD, 29}] in the intensive treatment group vs. 8.7 mmol/L [SD, 2.3] [157 mg/dL {SD, 42}] in the conventional treatment group; difference, -2.4 mmol/L [95% CI, -2.8 to -1.9 mmol/L] [-43 mg/dL {CI, -50 to -35 mg/dL}]). Eighty two of 185 patients (44%) in the intensive treatment group and 86 of 186 patients (46%) in the conventional treatment group had an event (risk ratio, 1.0 [CI, 0.8 to 1.2]). More deaths (4 deaths vs. 0 deaths; P = 0.061) and strokes (8 strokes vs. 1 strokes; P = 0.020) occurred in the intensive treatment group. Length of stay in the intensive care unit (mean, 2 days [SD, 2] vs. 2 days [SD, 3]; difference, 0 days [CI, -1 to 1 days]) and in the hospital (mean, 8 days [SD, 4] vs. 8 days [SD, 5]; difference, 0 days [CI, -1 to 0 days]) was similar for both groups.\n This single-center study used a composite end point and could not examine whether outcomes differed by diabetes status.\n Intensive insulin therapy during cardiac surgery does not reduce perioperative death or morbidity. The increased incidence of death and stroke in the intensive treatment group raises concern about routine implementation of this intervention.", "Patients with type 2 diabetes have abnormal endothelial function but it is not certain whether improvements in glycaemic control will improve endothelial function.\n To examine the effects of short-term improved glycaemic control on endothelial function in patients with inadequately regulated type 2 diabetes mellitus.\n Forty-three patients with type 2 diabetes and glycosylated haemoglobin (HbA1c) > 8.9% were randomized to either improved glycaemic control (IC) n = 21 or usual glycaemic control (UC) n = 22 for 20 weeks. Using high-resolution B-mode ultrasound, brachial artery flow-mediated dilatation (FMD) and glyceryl trinitrate-mediated dilatation (GTN-D) were measured at baseline and 20 weeks later.\n After 20 weeks, HbA1c was significantly lower in IC versus UC (IC 8.02 +/- 0.25% versus UC 10.23 +/- 0.23%, P < 0.0001) but changes in FMD and GTN-D were not different between the groups (FMD at baseline and week 20 IC 5.1 +/- 0.56% versus 4.9 +/- 0.56% and UC 4.2 +/- 0.51% versus 3.1 +/- 0.51%; P = 0.23: GTN-D IC 12.8 +/- 1.34% versus 10.4 +/- 1.32% and UC 13.7 +/- 1.2% versus 12.7 +/- 1.23%; P = 0.39). In the IC group weight increased by 3.2 +/- 0.8 kg after 20 weeks compared to 0.02 +/- 0.70 kg in UC (P = 0.003). Blood pressure and serum lipid concentrations did not change in either group.\n Short-term reduction of HbA1c levels did not appear to affect endothelial function in patients with type 2 diabetes and previously poorly regulated glycaemic control." ]	The included trials did not show significant differences for all-cause mortality and cardiovascular mortality when targeting intensive glycaemic control compared with conventional glycaemic control. Targeting intensive glycaemic control reduced the risk of microvascular complications while increasing the risk of hypoglycaemia. Furthermore, intensive glycaemic control might reduce the risk of non-fatal myocardial infarction in trials exclusively dealing with glycaemic control in usual care settings.
CD001547	[ "8738682", "10957701", "8197031", "10847283", "21257263", "2293142", "3690941", "3737440", "17022854", "19105251", "3461726", "1745622", "11589259", "2813153", "16085437", "6344039", "7963789", "12631041", "11498314", "3311548", "19487950", "20637958", "3365916", "10027033", "2082318", "16238896", "378734", "3072354" ]	[ "Additive analgesic effect of codeine and paracetamol can be detected in strong, but not moderate, pain after Caesarean section. Baseline pain-intensity is a determinant of assay-sensitivity in a postoperative analgesic trial.", "No effect of preoperative paracetamol and codeine suppositories for pain after termination of pregnancies in general anaesthesia.", "Evaluation of two opioid-acetaminophen combinations and placebo in postoperative oral surgery pain.", "Single-dose vicoprofen compared with acetaminophen with codeine and placebo in patients with acute postoperative pain after third molar extractions.", "A randomised, five-parallel-group, placebo-controlled trial comparing the efficacy and tolerability of analgesic combinations including a novel single-tablet combination of ibuprofen/paracetamol for postoperative dental pain.", "Codeine plus paracetamol versus paracetamol in longer-term treatment of chronic pain due to osteoarthritis of the hip. A randomised, double-blind, multi-centre study.", "The additive analgesic efficacy of acetaminophen, 1000 mg, and codeine, 60 mg, in dental pain.", "Analysis of the analgesic efficacy of acetaminophen 1000 mg, codeine phosphate 60 mg, and the combination of acetaminophen 1000 mg and codeine phosphate 60 mg in the relief of postoperative pain.", "Clinical equivalence of IV paracetamol compared to IV dipyrone for postoperative analgesia after surgery for breast cancer.", "[Analgesic and opioid-sparing effects of intravenous paracetamol in the early period after aortocoronary bypass surgery].", "Efficacy of low dose combination analgesics: acetaminophen/codeine, aspirin/butalbital/caffeine/codeine, and placebo in oral surgery pain.", "Analgesic efficacy of acetaminophen 1000 mg, acetaminophen 2000 mg, and the combination of acetaminophen 1000 mg and codeine phosphate 60 mg versus placebo in acute postoperative pain.", "Rofecoxib versus codeine/acetaminophen in postoperative dental pain: a double-blind, randomized, placebo- and active comparator-controlled clinical trial.", "Evaluation of flurbiprofen, acetaminophen, an acetaminophen-codeine combination, and placebo in postoperative oral surgery pain.", "Analgesic efficacy and safety of intravenous paracetamol (acetaminophen) administered as a 2 g starting dose following third molar surgery.", "A 12-hour evaluation of the analgesic efficacy of diflunisal, acetaminophen, and acetaminophen-codeine combination, and placebo in postoperative pain.", "The dose-response relationship of controlled-release codeine (Codeine Contin) in chronic cancer pain.", "Analgesic effect of i.v. paracetamol: possible ceiling effect of paracetamol in postoperative pain.", "Evaluation of the safety and efficacy of epidural ketamine combined with morphine for postoperative analgesia after major upper abdominal surgery.", "Analgesic efficacy of two ibuprofen-codeine combinations for the treatment of postepisiotomy and postoperative pain.", "Paracetamol versus metamizol in the treatment of postoperative pain after breast surgery: a randomized, controlled trial.", "A single-tablet fixed-dose combination of racemic ibuprofen/paracetamol in the management of moderate to severe postoperative dental pain in adult and adolescent patients: a multicenter, two-stage, randomized, double-blind, parallel-group, placebo-controlled, factorial study.", "A double-blind study of diflunisal and codeine compared with codeine or diflunisal alone in postoperative pain.", "Lack of pre-emptive analgesic effect of (R)-ketamine in laparoscopic cholecystectomy.", "Evaluation of ketorolac, ibuprofen, acetaminophen, and an acetaminophen-codeine combination in postoperative oral surgery pain.", "A comparison between IV paracetamol and IV metamizol for postoperative analgesia after retinal surgery.", "Analgesic combinations with orphenadrine in oral post-surgical pain.", "Double-blind parallel comparison of ketoprofen (Orudis), acetaminophen plus codeine, and placebo in postoperative pain." ]	[ "A randomized, double-blind, placebo-controlled single oral dose study was done in order to examine whether codeine has an additive analgesic effect to that of paracetamol for moderate and strong postoperative pain after abdominal surgery. The maximum recommended single dose of paracetamol 1000 mg (Paracet) was compared with a combination of a submaximal dose of paracetamol 800 mg plus codeine 60 mg (Paralgin forte) and placebo for pain relief after Caesarean section in 125 patients.\n Visual analogue pain intensity score (VAS 0-100 mm) and categorical pain relief score were recorded for 6 hours after the study drug intake. The main efficacy variables analyzed were: pain intensity difference and summed pain intensity differences during the first 3 and 6 h after study drug intake, total pain relief during the first 3 and 6 h, global evaluation score at the end of the observation period, and time to rescue analgesic.\n Because of protocol violations, 17 patients were excluded from the analysis of effects. Among the 108 patients included in the analysis of analgesic effect, 49 patients had moderate baseline pain (VAS between 40 and 60 mm on a 100 mm scale), and 59 patients had strong baseline pain (VAS more than 60 mm). In patients with strong baseline pain, statistically highly significant differences were documented in efficacy variables between the active drugs and placebo and between the two active drugs. However, in patients with moderate baseline pain, no differences were found between the study drugs in any of the analgesic efficacy variables.\n This study thus confirms that codeine has additive analgesic effect to paracetamol in pain after surgery. Our results show the importance of initial pain intensity in postoperative assessment of analgesic drugs. Assay-sensitivity and test power are increased by selecting patients with sufficiently high initial pain intensity and by comparing groups of patients with identical surgery and similar demographic variables.", "Outpatient surgery demands rapid recovery and satisfied patients. The purpose of the study was to investigate whether rectal premedication with paracetamol and codeine would reduce the need of rescue analgesics, reduce the postoperative pain experience and result in faster eligibility for discharge. Ninety pregnant patients scheduled for day-case surgery with evacuation of the uterine cavity were randomly assigned into two groups. The paracetamol and codeine group was given a suppository with 60 mg of codeine and 800 mg of paracetamol together with standard premedication of intramuscular midazolam 0.08 mg/kg. The placebo group was given a placebo suppository and midazolam. All patients underwent the surgical procedure under general anaesthesia with alfentanil 15 microg/kg and propofol 1.5-2 mg/kg. There were no statistically significant differences between the groups in the postoperative pain experience as judged by Visual Analogue Scale (VAS-scale), verbal scale or the need for rescue analgesic medication with ketobemidone. Most of the patients experienced little postoperative pain with more than 70% scoring less than 20 mm on a VAS-scale from 0-100 mm at any time during the postoperative period. The paracetamol and codeine patients were significantly more sleepy at 30 min postoperatively. There were no differences between the groups in postoperative nausea or vomiting and no difference in discharge eligibility. The use of pre-operative suppository with paracetamol 800 mg and codeine 60 mg is unnecessary in this group of patients.\n Copyright 2000 European Federation of Chapters of the International Association for the Study of Pain.", "To determine the relative analgesic potency and adverse effect liability of hydrocodone bitartrate 7.5 mg with acetaminophen 500 mg, codeine phosphate 30 mg with acetaminophen 300 mg, and placebo in the treatment of pain following oral surgery.\n Randomized, double-blind, single-dose, placebo-controlled, parallel-group study with self-ratings at 30 minutes and then at hourly intervals from hour 1 to hour 6.\n Private, oral surgery practice sites.\n Three hundred twenty-four outpatients with moderate or severe pain after the surgical removal of impacted third molars were selected. One was lost to follow-up and 32 did not need an analgesic; 232 patients had valid efficacy data.\n Patients were treated with a single oral dose of hydrocodone bitartrate 7.5 mg with acetaminophen 500 mg, codeine phosphate 30 mg with acetaminophen 300 mg, or placebo when they experienced steady, moderate or severe pain that, in their opinion, required an analgesic. Using a self-rating record, subjects rated their pain and its relief for 6 hours after medicating; estimates of peak and total analgesia were derived from these subjective reports.\n This study was a valid analgesic assay. Both active treatments were significantly superior to placebo for all measures of analgesic efficacy. The hydrocodone-acetaminophen combination was significantly superior to the codeine-acetaminophen combination for total pain relief and the number of evaluations with 50% relief. Both active treatments manifested an analgesic effect within 30 minutes; the effect persisted for 5 hours for the codeine combination and 6 hours for the hydrocodone combination. Adverse effects were transient, consistent with the pharmacologic profiles of opioids, and none required treatment.\n A slight advantage in analgesic efficacy was demonstrated in this single-dose study for the hydrocodone-acetaminophen combination. Repeat-dose studies, however, should be conducted to determine the clinical significance of the difference in analgesic effect of these opioid combinations.", "The purpose of this double-blind, randomized study was to compare the efficacy and safety of a single dose of the following medications: 2 tablets of Vicoprofen (ibuprofen 200 mg/hydrocodone 7.5 mg; Knoll Pharmaceutical Co, Mount Olive, NJ), 2 tablets ofp6 acetaminophen with codeine phosphate (acetaminophen 300 mg/codeine 30 mg), and 2 tablets of placebo in the management of moderate to severe postoperative dental pain after surgical extraction of at least one impacted mandibular third molar.\n One hundred twenty-five patients (75 women, 50 men) participated in the study. The time of first perceptible pain relief and meaningful pain relief were measured using a stopwatch technique. Pain intensity and pain relief scores were recorded using standard verbal descriptors at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, and 8 hours after dosing. At the conclusion of the study, patients completed a global evaluation for the effectiveness of the study medication.\n Both active treatments were superior to placebo for all analgesic measures. Pain relief scores were significantly better for Vicoprofen than placebo throughout the study and significantly better than for acetaminophen with codeine from 2 through 8 hours after dosing. The duration of analgesia (time to remedication) was significantly longer for Vicoprofen (median, 5.50 hours) compared with acetaminophen with codeine (median, 3.03 hours) and placebo (median, 1.00 hours). Mean global evaluation for Vicoprofen was significantly better than for placebo and acetaminophen with codeine. Overall, there were no significant differences in the adverse event profile among the 3 treatment groups.\n Vicoprofen was found to be an effective postoperative analgesic medication in the management of acute postoperative dental pain. Its total analgesic effect, duration of analgesia, and global evaluation were superior to acetaminophen with codeine and placebo in this study model.", "Combination analgesia is often recommended for the relief of severe pain. This was a double-blind, 5-arm, parallel-group, placebo-controlled, randomised, single-dose study designed to compare the efficacy and tolerability of a novel single-tablet combination of ibuprofen and paracetamol with that of an ibuprofen/codeine combination, and a paracetamol/codeine combination, using the dental impaction pain model. Subjects with at least 3 impacted third molars and experiencing moderate to severe postoperative pain were randomised to receive: 1 or 2 tablets of a single-tablet combination of ibuprofen 200mg/paracetamol 500mg; 2 tablets of ibuprofen 200 mg/codeine 12.8mg; 2 tablets of paracetamol 500mg/codeine 15mg; or placebo. Results for the primary endpoint, the sum of the mean scores of pain relief combined with pain intensity differences over 12hours, demonstrated that 1 and 2 tablets of the single-tablet combination of ibuprofen/paracetamol were statistically significantly more efficacious than 2 tablets of placebo (P<0.0001) and paracetamol/codeine (P⩽0.0001); furthermore, 2 tablets offered significantly superior pain relief to ibuprofen/codeine (P=0.0001), and 1 tablet was found noninferior to this combination. Adverse events were uncommon during this study and treatment emergent adverse events were statistically significantly less frequent in the groups taking the ibuprofen/paracetamol combination compared with codeine combinations. In conclusion, 1 or 2 tablets of a single-tablet combination of ibuprofen 200mg/paracetamol 500mg provided highly effective analgesia that was comparable with, or superior to, other combination analgesics currently indicated for strong pain. A single-tablet combination of ibuprofen 200mg/paracetamol 500mg provides highly effective analgesia, comparable or superior to other combination analgesics indicated for strong pain.\n Copyright © 2011. Published by Elsevier B.V.", "This randomized, double-blind, multi-centre study was undertaken to evaluate the efficacy and safety of treatment for 4 weeks with codeine plus paracetamol versus paracetamol in relieving chronic pain due to osteoarthritis of the hip. A total of 158 outclinic patients entered the study. Eighty-three patients (mean age 66 years) were treated with codeine 60 mg plus paracetamol 1 g 3 times daily, and 75 patients (mean age 67 years) with paracetamol 1 g 3 times daily. Ibuprofen 400 mg was prescribed as rescue medication. Due to an unexpected high rate of adverse drug reactions, the study was closed before the planned 400 patients had entered. Over weeks 1-4, 87%, 64%, 61% and 52% of patients in the codeine plus paracetamol group, and 38%, 31%, 22% and 29% of patients in the paracetamol group had one or more adverse drug reactions. Significantly more patients in the codeine plus paracetamol group had adverse drug reactions in each of the 4 weeks. Nausea, dizziness, vomiting and constipation were predominant adverse reactions in the codeine plus paracetamol group. During the first week of treatment, 30 patients (36%) in the codeine plus paracetamol group and 9 (12%) in the paracetamol group dropped out. As evaluated from patients completing the first week of treatment, the pain intensity during that week compared to their baseline pain was significantly lower in the codeine plus paracetamol group than in the paracetamol group. Moreover, during the first week the paracetamol group received rescue medicine significantly more frequently. In conclusion, when evaluated after 7 days of treatment, the daily addition of codeine 180 mg to paracetamol 3 g significantly reduced the intensity of chronic pain due to osteoarthritis of the hip joint. However, several adverse drug reactions, mainly of the gastrointestinal tract, and the larger number of patients withdrawing from treatment means that the addition of such doses of codeine cannot be recommended for longer-term treatment of chronic pain in elderly patients.", "In a double-blind, randomized, single-dose trial the analgesic contribution of acetaminophen, 1000 mg, and codeine, 60 mg, was determined. The study was a 2 X 2 factorial experiment in which 120 patients suffering from pain as a result of oral surgery rated their pain intensity and pain relief for up to 5 hours after a single dose of one of: 1000 mg acetaminophen, 60 mg codeine, 1000 mg acetaminophen plus 60 mg codeine, or placebo. The factorial analysis showed that both 1000 mg acetaminophen and 60 mg codeine made a statistically significant (P less than 0.05) contribution to the analgesic effectiveness of the combination on all measures of efficacy (sum of pain intensity differences, largest pain intensity difference, total pain relief, largest pain relief, and time to remedication). The incidence of adverse effects did not appear to differ among the treatments, including placebo.", "Patients who experienced pain after surgery were administered a single dose of 1 of 3 treatments: acetaminophen 1000 mg, codeine phosphate 60 mg, or a combination of these. Patients rated their pain intensity on ordinal and visual analog scales just prior to medication and at intervals thereafter for up to 5 hours. They also rated pain relief, pain half gone, and any adverse effects. Sum of pain intensity difference and total pain relief scores were analyzed using Dunnett's procedure. The drug combination was statistically superior to codeine as measured by SPID, TOTPAR, pain half gone, and time to remedication. The combination achieved better mean scores than acetaminophen on all efficacy measures, but was (marginally) statistically superior only in pain half gone. No appreciable differences in adverse effects were noted among the treatments. The difficulty of showing the analgesic efficacy of codeine in a single dose trial is discussed.", "To assess clinical efficacy of IV paracetamol 1 g and IV dipyrone 1 g on a 24-h dosing schedule in this randomised, double-blinded study of 40 ASA I-III (American Society of Anesthesiologists classification of physical status) patients undergoing surgery for breast cancer.\n General anaesthesia using remifentanil and propofol was performed for surgery. The patients were randomly allocated to two groups, receiving infusions of paracetamol 1 g/100 mL (Para Group) or of dipyrone 1 g/100 mL (Dipy Group) 30 min before arrival in the recovery area and every 6 h up to 24 h postoperatively. All patients had unrestricted access to opioid rescue medication via an IV patient-controlled analgesia (PCA) device.\n The primary variables for clinical equivalence were the differences between the mean values for pain scores at rest and pain scores on coughing over 30 h postoperatively. The equivalence margin was determined as +/-10 mm on the visual analogue scale (VAS).\n Regarding pain scores at rest, the 90% CI of the mean differences between the treatment groups over 30 h postoperatively was found to be within the predefined equivalence margin [+7.5/-6.2], and the CI values for pain scores on coughing [+7.3/-9.0] were similar. The two groups did not differ in cumulative opioid rescue consumption (Dipy-Group 14.8 +/- 17.7 mg vs. Para Group 12.1 +/- 8.8 mg, p = 0.54) nor in piritramide loading dose (Dipy Group 0.95 +/- 2.8 mg vs. Para Group 1.3 +/- 2.8 mg, p = 0.545). Five patients in the Dipy Group experienced hypotension in contrast to none in the Para Group (p = 0.047). There were no significant between-treatment differences for other adverse events, patient satisfaction scores (p = 0.4) or quality of recovery scores (p = 0.3).\n IV paracetamol 1 g is clinically equivalent to IV dipyrone 1 g for postoperative analgesia after surgery for breast cancer.", "The study was to evaluate the analgesic and opioid-sparing effect of intravenous paracetamol injections in cardiosurgical patients in the early postoperative period. Adequate analgesia within the first 12-18 hours of the early postoperative period is very important for a good prognosis of the further course of pain syndrome and for the reduction of a risk for its progression to its chronic form. In early studies, propacetamol lowered morphine use after orthopedic and gynecological operations. The efficacy of paracetamol used in cardiac surgery has been little studied and the results of the studies are conflicting. The randomized, blind, placebo-controlled study included patients after aortocoronary bypass surgery, of them 22 patients received paracetamol and 23 had placebo. The test drug (perfalgan 100 ml or placebo) was intravenously injected 30 min before extubation and then every 6 hours within succeeding 18 hours. The intensity of the pain syndrome was rated by a 5-score verbal scale every 2 hours. With pain score of 2 or more, promedol was intramuscularly administered in a dose of 10 mg. Inspiratory volume was recorded before extubation and the first administration of a drug just after extubation and then every 2 hours. The baseline indices did not differ in both groups. Throughout the observation, the inspiratory volume was lower in the paracetamol group than in the placebo group; however, there was a statistically significant difference (p = 0.012) in the reduction in the manifestations of the pain syndrome (by 81%) only just after tracheal extubation. During this period, inspiratory volume values were higher in the paracetamol group; however, a statistically significant (39%) difference between the groups in the mean values was obtained only during and 2 hours after extubation. In the perfalgan group, the mean total use of promedol was 36% less than in the placebo-group, which was statistically significant (p = 0.019). The early postoperative use of paracetamol after myocardial revascularization reduces the intake of opioids and diminishes the intensity of the pain syndrome within the first hours after extubation, which promotes a higher thoracic excursion, as confirmed by a statistically significant increase in the maximum inspiratory capacity.", "A double-blind, randomized, single-dose study was performed to compare the efficacy and safety of two commonly prescribed combination analgesic products to placebo. The combinations were acetaminophen 300 mg/codeine 30 mg(†), and aspirin 325 mg/butalbital 50 mg/caffeine 40 mg/codeine 30 mg(††). One hundred twenty-three (123) oral surgery outpatients took study medications when their pain became moderate to severe and recorded the levels of pain intensity, pain relief, anxiety and relaxation at 30 minutes and hourly for 6 hours after dosing. Remedication was permitted if study medications did not provide adequate pain relief. Time to remedication, and the number of observations with 50% or better relief, were noted as were any side effects. An overall evaluation was obtained from each patient. Results of the study showed that the aspirin/butalbital/caffeine/codeine combination was significantly more effective than placebo for total pain relief, peak relief and global evaluation. While the acetaminophen/codeine combination was numerically superior to placebo, it achieved statistical significance only for global evaluation. The aspirin/butalbital/caffeine/codeine combination was numerically superior to acetaminophen/codeine for every measure of analgesic efficacy but the differences did not achieve statistical significance. Both active treatment groups experienced significantly less total anxiety than did the placebo group. Only 11 patients reported mild, transient adverse effects; the most common was drowsiness. The adverse effects occurred equally among the three treatment groups. In this study, the aspirin/butalbital/caffeine/codeine combination was significantly superior to placebo and somewhat better than acetaminophen/codeine.", "Acetaminophen (APAP) 1000 mg, APAP 2000 mg, the combination of APAP 1000 mg plus codeine phosphate 60 mg (APAPCOD), and placebo (PBO) were compared in a 6-hour, randomized, single-dose, double-blind, parallel-group analgesic trial. All active treatments were statistically superior (p less than 0.05) to placebo for 4 hours after medication with respect to pain intensity (PI) and pain intensity difference (PID), and up to 3 hours regarding pain relief (PAR). The combination scored better than all other treatments on the summary analgesic efficacy measures sum PI (SUMPI), sum PID (SPID), and total PAR (TOTPAR). The combination was statistically superior to APAP 1000 mg on SUMPI, TOTPAR and maximum PAR (MAXPAR). Acetaminophen 2000 mg showed marginal numerical superiority over 1000 mg for SUMPI, but was not statistically superior for any summary efficacy measure. The 2000-mg dose was numerically inferior to APAPCOD for every summary efficacy measure and statistically inferior regarding SPID and MAXPAR. We concluded that codeine 60 mg added to acetaminophen 1000 mg offers analgesic advantages, and acetaminophen reaches an analgesic ceiling effect at 1000 mg using the dental pain model.", "In recent studies of acute pain and primary dysmenorrhea, rofecoxib, a nonsteroidal anti-inflammatory drug that selectively targets the cyclooxygenase-2 enzyme, was found to be similar in efficacy to ibuprofen and naproxen sodium.\n The purpose of this study was to determine the analgesic efficacy of a single oral dose of rofecoxib 50 mg compared with the combination of codeine 60 mg/acetaminophen 600 mg in a model of postsurgical dental pain.\n In this double-blind, placebo- and active comparator-controlled, parallel-group study, patients experiencing moderate or severe pain after the surgical extraction of > or = 2 third molars, at least 1 of which was a mandibular impaction, were randomized to receive placebo, rofecoxib 50 mg, or codeine 60 mg/acetaminophen 600 mg. Patient evaluations of pain intensity, pain relief, and global assessments were recorded throughout the 24-hour period after dosing. The 2-stopwatch method was used to determine time to confirmed perceptible pain relief. The primary end point assessing overall analgesic effect was total pain relief over 6 hours (TOPAR6). Secondary end points were patient global assessment of response to therapy (PGART) at 6 hours, onset of analgesia, peak analgesic effect, and duration of analgesia.\n A total of 393 patients were enrolled; 182 received rofecoxib, 180 received codeine/acetaminophen, and 31 received placebo. The overall analgesic effect of rofecoxib 50 mg was greater than that of codeine 60 mg/acetaminophen 600 mg for TOPAR6 (12.4 vs 7.0; P < 0.001) and PGART at 6 hours (P < 0.001). The onset of analgesic effect was similar for rofecoxib and codeine/acetaminophen. Peak analgesic effect as measured by peak pain relief scores during the first 6 hours was significantly greater in the rofecoxib group compared with the codeine/acetaminophen group (P < 0.001), as was the duration of analgesic effect measured by the time to rescue analgesia (9.6 hours vs 2.3 hours, P < 0.001). Adverse events were reported in 33.0%, 46.1%, and 32.3% of patients treated with rofecoxib, codeine/acetaminophen, and placebo, respectively. The most common adverse events were nausea (6.0%, 25.0%, and 9.7%, respectively) and vomiting (3.8%, 18.3%, and 6.5%, respectively). Significantly more patients in the codeine/acetaminophen group than in the rofecoxib group experienced adverse events overall (P < 0.050) and nausea in particular (P < 0.001).\n In this study of moderate to severe postoperative dental pain, the analgesic efficacy of rofecoxib 50 mg was greater than that of codeine/acetaminophen, with a lower incidence of adverse events and nausea.", "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 recommended dose for intravenous (IV) paracetamol injection in adults is 1g, however pharmacokinetic and pharmacodynamic findings suggest that a better analgesia could be obtained with a 2 g starting dose.\n A single-centre, randomised, double-blind, placebo-controlled, 3-parallel group study was performed to demonstrate the analgesic efficacy and safety of IV paracetamol 2 g. Following third molar surgery, patients reporting moderate to severe pain received a single 15-min infusion of either IV paracetamol 2 g, IV paracetamol 1g or placebo. Efficacy and safety were evaluated over 8 h. Laboratory tests were performed before and 48 h after drug administration.\n Two hundred and ninety seven patients (132 = IV paracetamol 2g; 132 = IV paracetamol 1g; 33 = placebo) were randomised and completed the study. The summed pain relief over 6h (TOTPAR6) was significantly superior with IV paracetamol 2 g as compared to IV paracetamol 1g and placebo (p < 0.0001). Pain relief scores of IV paracetamol 2g were significantly superior to IV paracetamol 1g and to placebo from T30' to T8h (p < 0.0001). Median duration of analgesia was significantly longer following IV paracetamol 2 g compared to IV paracetamol 1g and placebo (p < 0.0001). Adverse events occurred with the same frequency in the 3 treatment groups. No clinically significant changes from baseline were observed for vital signs or laboratory tests.\n The analgesic efficacy of a 2 g starting dose of IV paracetamol was superior over the recommended dose of 1g in terms of magnitude and duration of analgesic effect for postoperative pain following third molar surgery, with no significant difference between groups regarding safety.", "The analgesic efficacy of single 500 and 1,000 mg doses of diflunisal, a new nonsteroidal antiinflammatory analgesic, was compared in a double-blind study with acetaminophen 600 mg, the combination of acetaminophen 600 mg with codeine 60 mg, and placebo in 132 inpatients with postoperative pain. Using a self-rating record, patients rated their pain and its relief hourly for up to 12 hours after medication. Diflunisal 500 and 1,000 mg were significantly superior to placebo for every measure of total and peak analgesia, and a significant analgesic effect persisted for 8 hours. Acetaminophen alone and the acetaminophen-codeine combination were significantly superior to placebo for most measures of analgesia, and their effects were significant for 4 and 5 hours respectively. Differences among the active medications were not statistically significant for measures of total or peak analgesia.", "The improved pain control provided by regular dosing of opioid analgesics in patients with severe cancer pain has been well established. However, the treatment of mild-to-moderate cancer pain is often limited to \"as needed\" dosing with fixed combinations of codeine or oxycodone plus a nonopioid analgesic, which do not allow optimal titration of the individual components. This randomized double-blind study was designed to evaluate the efficacy of controlled-release codeine (Codeine Contin) in patients with cancer pain, and to estimate its dose equivalence to a standard combination of acetaminophen plus codeine. Twenty-four patients with at least moderate cancer pain were randomized to Codeine Contin 100, 200, or 300 mg every 12 hr or acetaminophen plus codeine (600 mg/60 mg) every 6 hr. On days 1 and 4 of dosing, pain intensity and pain relief were assessed hourly for 12 hr. The sum of pain intensity differences (SPID) from baseline and the total pain relief (TOTPAR) scores demonstrated a dose-response relationship for Codeine Contin on days 1 and 4 that was statistically significant on day 1 and suggested greater analgesic efficacy on day 4, compared with day 1. Codeine Contin 150 mg every 12 hr was estimated to be equianalgesic to acetaminophen plus codeine (600 mg/60 mg) given every 6 hr. Because a similar equivalence was also demonstrated from analysis of adverse event data, it is concluded that Codeine Contin 150 mg produces analgesia and a side-effect profile similar to a 40% lower dose of codeine provided by the combination.(ABSTRACT TRUNCATED AT 250 WORDS)", "Despite the widespread use of paracetamol for many years, the analgesic serum concentrations of paracetamol are unknown. Therefore the correlation between serum paracetamol concentrations and the analgesic effect was studied.\n Sixty-four women undergoing laparoscopic sterilization were included in a double-blind, placebo-controlled, randomized study. Patients were given i.v. propacetamol 40 mg kg(-1) (group H), 20 mg kg(-1) (group I), 10 mg kg(-1) (group L) or placebo after surgery. Alfentanil was available via patient-controlled analgesia (PCA) during the 4-h postoperative study period. The patients' self-reported pain was registered on the visual analog scale (VAS). A pharmacokinetic model was fitted to the paracetamol data.\n One to 3 h after injection of propacetamol the alfentanil consumption was significantly (P = 0.01-0.04) higher in the placebo group compared with groups H, I, and L receiving propacetamol. There were no significant differences between the amounts of alfentanil consumed in groups H, I, and L. Initial VAS-scores were moderate (5.4-6.2), and declined significantly (P < 0.0001) over time, with no difference between groups. Paracetamol followed an open two-compartment model with i.v. administration and first order elimination. The estimated concentrations immediately (t = 0) after injection were 56 mg l(-1) (H), 28 mg l(-1) (I) and 14 mg l(-1) (L).\n We showed a significant opioid-sparing effect of paracetamol in the immediate postoperative period. Pharmacokinetic data were in accordance with other studies. Our results suggest that a ceiling effect of paracetamol may be present at i.v. doses of 5 mg kg(-1), i.e. a serum concentration of 14 mg l(-1), which is a lower dose than previously suggested.\n Copyright Acta Anaesthesiologica Scandinavica 47 (2003)", "To evaluate the efficacy of the combination of epidural ketamine and morphine compared with epidural morphine alone for postoperative pain relief following major upper abdominal surgery.\n Prospective, randomized, double-blinded study.\n Tertiary care referral and teaching hospital.\n 46 ASA physical status I and II patients who underwent major upper abdominal procedures.\n Patients were randomly allocated to one of the two treatment groups: patients in Group 1 received epidural morphine 50 microg/kg whereas patients in Group 2 received epidural ketamine 1 mg/kg combined with 50 microg/kg of morphine postoperatively.\n A blinded observer using a visual analog scale (VAS) for pain assessment followed up patients for 48 hours postoperatively. Top-up dose of epidural morphine was provided when VAS was higher than 4. Analgesic requirements and side effects were compared between the two groups.\n Only 40 patients completed the study. There were no differences between the two groups with respect to age, gender, weight, duration, or type of surgical procedure or intraoperative opioid requirements. Onset of analgesia was faster (p < 0.001) in Group 2 (11 min) than in Group 1 patients (25 min). The time for first requirement of analgesia was significantly (p < 0.01) longer (19.8 +/- 9.8 hours) in Group 2 patients than Group 1 (12.8 +/- 6.2 hours). Total number of supplemental doses of epidural morphine required in the first 48 hours postoperatively was also significantly less (p < 0.005) in Group 2 compared to Group 1. Patients in Group 2 had higher sedation scores than Group I patients for the first 2 hours postoperatively. None of the patients in either group developed hallucinations or respiratory depression. Other side effects such as pruritus, nausea, and vomiting were also similar in both groups.\n The addition of epidural ketamine 1 mg/kg to morphine 50 microg/kg improved analgesia after major upper abdominal surgery without increasing side effects.", "Our purpose was to compare the analgesic efficacy and safety of single oral doses of the combination of ibuprofen 400 mg plus codeine 60 mg and the combination of ibuprofen 200 mg plus codeine 30 mg with ibuprofen 400 mg alone, codeine sulfate 60 mg alone, and placebo. One hundred ninety-five patients with severe pain resulting from episiotomy, cesarean section, or gynecologic surgery completed a randomized, double-blind, stratified, parallel-group study. Patients were observed during a 4-hour period after medication. Based on the sum of the pain intensity differences (SPID), total pain relief (TOTPAR), and most of the hourly direct measures of pain and relief, both doses of the combination and ibuprofen 400 mg alone were statistically superior to placebo. Codeine 60 mg was statistically superior to placebo based on TOTPAR, the global ratings, and a few hourly measures. The mean effect of the combination of ibuprofen 400 mg plus codeine 60 mg was significantly superior to the mean effect of ibuprofen 400 mg alone 1/2, 1, and 2 hours after medication and to the mean effect of ibuprofen 400 mg alone and codeine 60 mg alone for SPID, TOTPAR, and other measures as well. The low-dose combination was significantly more effective than codeine 60 mg for a few hourly measures but was not significantly superior to ibuprofen 400 mg. Based on these findings it appears that the combination of ibuprofen 400 mg plus codeine 60 mg, particularly in the first few hours after medication, is more efficacious than its constituents.", "Intravenously administered paracetamol is an effective analgesic in postoperative pain management. However, there is a lack of data on the effect of intravenous (i.v.) paracetamol on pain following soft tissue surgery.\n Eighty-seven patients undergoing elective breast surgery with total i.v. anaesthesia (propofol/remifentanil) were randomized to three groups. Group para received 1 g i.v. paracetamol 20 min before and 4, 10 and 16 h after the end of the operation. Group meta and plac received 1 g i.v. metamizol or placebo, respectively, scheduled at the same time points. All patients had access to i.v. morphine on demand to achieve adequate pain relief.\n No significant difference in total morphine consumption between groups was detectable. The proportion of patients who did not receive any morphine in the postoperative period was significantly higher in group para (42%) than in group plac (4%). Ambulation was significantly (P < 0.05) earlier in group para (4.0 +/- 0.2 h) than in groups meta (4.6 +/- 0.2 h) and plac (5.5 +/- 1.0 h). No differences were observed between groups meta and plac. There were no differences between groups with regard to incidence of postoperative nausea and vomiting or changes in vigilance.\n Neither i.v. paracetamol nor i.v. metamizol provided a significant reduction in total postoperative morphine consumption compared with placebo in the management of postoperative pain after elective breast surgery. Administration of paracetamol resulted in a significant reduction in the number of patients needing opioid analgesics to achieve adequate postoperative pain relief.", "The combination of ibuprofen and paracetamol may confer analgesic benefits over monotherapy with either agent. In a previous study, an ibuprofen/paracetamol combination provided significantly better analgesic efficacy than comparable doses of ibuprofen or paracetamol alone in patients experiencing moderate to severe acute postoperative pain after extraction of impacted third molars.\n This study compared the efficacy and tolerability of 3 doses of a single-tablet fixed-dose combination (FDC) of ibuprofen and paracetamol (ibuprofen/paracetamol doses of 100 mg/250 mg, 200 mg/500 mg, and 400 mg/1000 mg) with comparable doses of ibuprofen (200 or 400 mg) monotherapy, paracetamol (500 or 1000 mg) monotherapy, and placebo in the 8 hours after surgical removal of 3 to 4 impacted third molars (stage 1) and with placebo over the next 72 hours (stage 2).\n This was a multicenter, 2-stage, randomized, double-blind, parallel-group, placebo-controlled, factorial study. Male or female outpatients were eligible for the study if they were aged >or=16 years, were referred for surgical removal of at least 3 impacted third molars (2 of which had to be mandibular impacted molars), and gave written informed consent. In stage 1, patients were randomly assigned to ibuprofen 200 mg, ibuprofen 400 mg, paracetamol 500 mg, paracetamol 1000 mg, FDC ibuprofen 100 mg/paracetamol 250 mg, FDC ibuprofen 200 mg/paracetamol 500 mg, FDC ibuprofen 400 mg/paracetamol 1000 mg, or placebo. In stage 2, patients who had been taking FDC therapy or placebo continued the same treatment, whereas those taking monotherapy received FDC therapy, incorporating the same dose of active monotherapy from stage 1. First-line rescue medication (hydrocodone 7.5 mg and paracetamol 500 mg) was available at any time after dosing; however, in stage 1, any patient who required rescue medication within 60 minutes of receipt of study medication was considered a \"dropout\" from therapy, and, in stage 2, patients who required >2 doses of first-line rescue medication in a 24-hour period were considered treatment failures. In stage 1, the primary efficacy end points were the sum of pain relief and pain intensity differences over an 8-hour follow-up period (SPRID8) and the pain relief and pain intensity difference scores at each time point (15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 420, and 480 minutes after dosing). Several secondary variables were also measured, including the patient's global assessment of the study medication. The 2-stopwatch method was used for measures of perceptible and meaningful pain relief. In stage 2, the primary efficacy end point was the number of completed 24-hour periods (as 0, 1, 2, or 3) in which the patient required no more than one dose of rescue medication and rated the treatment as \"good,\" \"very good,\" or \"excellent.\" The tolerability of study medications was assessed in relation to the frequency, nature, and severity of adverse events (AEs), as well as their relationship to study medication; vital signs were also measured. AEs were assessed at 8 hours after dosing in stage 1, at 72 hours after dosing in stage 2, and at the follow-up visit (7-10 days after surgery); in addition, patients were instructed to report any AE that occurred between scheduled assessments.\n Of 735 patients randomly assigned in stage 1, a total of 715 (97.3%) entered and 678 (92.2%) completed stage 2. Most patients were female (62.6% [460/735]) and white (91.3% [671/735]); the mean (SD) age was 20.3 (3.5) years and the mean weight was 69.7 (15.7) kg. The mean total impaction score was 11.1 (1.4), and the mean baseline pain score on the visual analog scale was 76.9 (12.0). Overall, 422 of 735 patients (57.4%) reported severe pain at baseline and 313 of 735 (42.6%) reported moderate pain. For the primary efficacy end point (SPRID8), FDC ibuprofen 400 mg/paracetamol 1000 mg was significantly more effective than ibuprofen 400 mg (P = 0.02) and paracetamol 1000 mg (P < 0.001) in the immediate postoperative period (stage 1), and FDC ibuprofen 200 mg/paracetamol 500 mg was significantly more effective than ibuprofen 200 mg (P < 0.001) and paracetamol 500 mg (P < 0.001). The FDC ibuprofen 200 mg/paracetamol 500 mg was also significantly more effective than paracetamol 1000 mg (P < 0.001), but failed to reach statistical significance in comparison with ibuprofen 400 mg. Continued postoperative therapy with all 3 FDCs on an as-needed basis was significantly more effective than placebo during the subsequent 72 hours (all, P < 0.001). During stage 1, rescue medication was required by 53 of 73 (72.6%), 29 of 75 (38.7%), 21 of 74 (28.4%), 56 of 76 (73.7%), and 51 of 74 (68.9%) patients in the placebo group and the ibuprofen 200-mg, ibuprofen 400-mg, paracetamol 500-mg, and paracetamol 1000-mg treatment groups, respectively. In the FDC treatment groups, the need for rescue medication included 27 of 71 (38.0%), 40 of 143 (28.0%), and 32 of 149 (21.5%) patients in the ibuprofen 100-mg/paracetamol 250-mg, ibuprofen 200-mg/paracetamol 500-mg, and ibuprofen 400-mg/paracetamol 1000-mg groups, respectively. The rates of treatment-related AEs between the first and second doses of study medication were significantly lower for FDC ibuprofen 400 mg/paracetamol 1000 mg (8/149 patients [5.4%]) than for placebo (14/73 [19.2%]; P < 0.01) and paracetamol 1000 mg (10/74 [13.5%]; P < 0.05); and also lower for FDC ibuprofen 200 mg/paracetamol 500 mg (9/143 [6.3%]) compared with ibuprofen 200 mg (12/75 [16.0%]; P < 0.05) and paracetamol 500 mg (17/76 [22.4%]; P < 0.001).\n FDC ibuprofen 200 mg/paracetamol 500 mg and ibuprofen 400 mg/paracetamol 1000 mg were significantly more effective in this population than were comparable doses of ibuprofen or paracetamol alone in moderate to severe acute dental pain and were significantly more effective than placebo in providing sustained pain relief.", "A double-blind, randomized, parallel-group study compared the analgesic efficacy of a single oral dose of 500 mg diflunisal, 60 mg codeine, 500 mg diflunisal plus 60 mg codeine given as separate agents, and placebo in 161 patients with moderate to severe postoperative pain. Standard subjective measures were used to evaluate analgesia. Eight-hour sum of pain intensity differences and total pain relief scores for all active treatments were significantly better than were those for placebo (p less than 0.05). Diflunisal plus codeine performed the best followed by diflunisal, codeine, and placebo. Diflunisal plus codeine was better than placebo from 1 1/2 to 8 hours (p less than 0.01), better than codeine from 1 1/2 to 6 hours (p less than 0.05), and better than diflunisal alone from 1/2 to 1 1/2 hours (p less than 0.05) for most measures of analgesia. Factorial analysis demonstrated a significant early codeine effect and a significant diflunisal effect throughout. No significant treatment group differences were observed regarding adverse effects. Our data demonstrate that diflunisal plus codeine is generally well tolerated and provides analgesia superior to that of diflunisal or codeine alone in the treatment of moderate to severe postoperative pain.", "This study evaluated the pre-emptive analgesic effect of intravenous (i.v.) (R)-ketamine in laparoscopic cholecystectomy. (R)-ketamine was used due to the lower incidence of side-effects.\n Sixty patients who underwent surgery under general anesthesia were randomly allocated to 3 groups and studied in a double-blind manner. Two i.v. injections were administered: one after induction of anesthesia, approximately 3 min before surgery, and one after surgery. The placebo group (PLA, n = 20) received saline in both injections. The preoperative group (PRE, n = 20) received (R)-ketamine 1 mg/kg and then saline. The postoperative group (POST, n = 20) received saline and then (R)-ketamine 1 mg/kg. Postoperatively, the patients used a patient-controlled analgesia (PCA) pump. Pain was evaluated with a visual analog scale (VAS) at 30 min and every hour for 4 h and with a verbal rating scale (VRS) at 24 h and after 7 days.\n There were no occurrence of side-effects from (R)-ketamine. VAS and VRS at 1, 2, 3, and 4 h postoperatively showed no statistical differences. In the POST group, extubation was delayed and pain score (VAS) at 30 min postoperatively was significantly lower (P < 0.05) than the two other groups. There were no statistical differences in meperidine consumption during the first 4 h postoperatively and no differences in consumption of analgesics at 24 h and 7 days.\n In this study a 1 mg/kg dose of (R)-ketamine given at the end of surgery exerted a short-lasting hypnotic and analgesic effect. The same dose given preoperatively did not show postoperative analgesic effect or pre-emptive effect.", "Two-hundred six outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned on a double-blind basis to receive oral doses of ketorolac tromethamine 10 and 20 mg, ibuprofen 400 mg, acetaminophen 600 mg, a combination of acetaminophen 600 mg plus codeine 60 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 6 hours after medicating. All active medications were significantly superior to placebo. Analgesia was similar for ketorolac 10 and 20 mg and ibuprofen 400 mg; however, these treatments were superior to acetaminophen alone and the acetaminophen-codeine combination. The analgesic effect of each active medication was significant by hour 1 and persisted for 5-6 hours. The data suggest a plateau in ketorolac's analgesic efficacy at the 10-mg level. Repeat-dose data indicated that on the day of surgery ketorolac 10 and 20 mg and ibuprofen 400 mg were superior to acetaminophen 600 mg; ketorolac 20 mg was also superior to acetaminophen-codeine. Differences among active medications were not significant when data for the entire postoperative period (days 0-6) were evaluated. The frequency of adverse effects was similar for the active medications.", "To assess clinical efficacy of IV paracetamol 1 g and IV metamizol 1 IV metamizol 1 g on a 24-h dosing schedule in this randomized, double-blinded, placebo-controlled study of 38 ASA physical status I-III patients undergoing retinal surgery.\n General anaesthesia using remifentanil, propofol, and desflurane was performed for surgery. The patients were randomly allocated to three groups, receiving infusions of paracetamol 1 g/100 mL (Para Group), of metamizol 1 g/100 mL (Meta Group), or of 100 mL of saline solution as placebo control (Plac Group) 30 min before arrival in the recovery area and every 6 h up to 24 h postoperatively. All patients had unrestricted access to intravenous opioid rescue medication.\n The primary efficacy variables were pain scores at rest over 30 h postoperatively analysed by using repeated ANOVA measurement. Secondary efficacy variables were pain scores on coughing, also analysed by repeated ANOVA measurement.\n Five patients in the Plac Group and one patient in the Meta Group interrupted the study protocol. Regarding pain scores at rest, Mauchly-test of sphericity was significant (p = 0.03). For the p time effects a significant result was detected (p < 0.001). The main effect between the three treatment groups was significantly different (p = 0.01). The Bonferroni adjusted pair wise comparisons between p the Plac Group and the Para Group showed a significant difference in favour of IV paracetamol (p = 0.024; mean difference 14.8; p 95% CI 1.6-28.0), between the Plac Group and the Meta Group in favour of IV metamizol (p = 0.025; mean difference 14.4; 95% CI p 1.5-27.4), and no significant difference between the Para Group and the Meta Group (p = 1.0; mean difference 0.4; 95% CI-12.8 to 13.6). Pain scores on coughing showed a significant different main effect between the three treatment groups (p = 0.022). The Bonferroni adjusted pair wise comparisons between the Plac Group and the Para Group showed a significant difference in favour of IV paracetamol (p = 0.032; mean difference 17.9; 95% CI 1.3-34.6), a p difference, though not reaching statistical significance, in favour of IV metamizol between the Plac Group and the Meta Group (p = 0.081; p mean difference 15.0; 95% CI -1.4 to 31.4), and no significant difference between the Para Group and the Meta Group (p = 1.0; p mean difference 2.9; 95% CI -13.8 6 to 19.6). None of the patients experienced itching; one patient in the Meta Group developed a mild erythema. There was no statistical difference in the incidence of nausea (Plac vs. Para Group: p = 0.94, Plac vs. Meta Group: p = 0.98, Para vs Meta Group: p = 0.95) or vomiting (Plac vs. Para Group: p = 0.73, Plac vs. Meta Group: p = 0.85, Para vs Meta Group: p = 0.86) between the groups. Patients in the Plac Group experienced significantly more often sedation than patients in the Meta Group (p = 0.049). There was a trend of higher sedation in the Plac Group than in the Para Group, which did not reach statistical significance (p = 0.07). There was no difference in sedation between the Meta and the Para Groups (p = 0.84).\n IV paracetamol 1 g has a similar analgesic potency as IV metamizol 1 g for postoperative analgesia after retinal surgery.", "Two hundred male and female patients underwent a variety of oral surgical procedures and were treated afterwards in four test groups. They took a combination of orphenadrine (25 mg) and acetaminophen (325 mg), either drug alone, or placebo. A double-blind study design was used. All patients had moderately severe baseline pain intensity; post-treatment pain relief was recorded at 30 minutes, one, two, four and six hours. A back-up analgesic (codeine-ASA) was made available if needed. Pain intensity difference (PID) and sums of pain intensity difference (SPID) were calculated using established analgesic study techniques. Statistical analyses indicated better analgesic efficacy in both PID and SPID scores for the orphenadrine-acetaminophen combination over the three other treatments. This was evident at 30 minutes and continued through the sixth hour. Each active drug, in turn, was also significantly better throughout than placebo for pain relief. Sub-groups in each treatment regimen required additional pain relief prior to six hours, with significantly more placebo than orphenadrine-acetaminophen patients needing remedication. Side-effect incidence was very low and randomly distributed among the four groups.", "One hundred sixty-one patients with postoperative pain were treated at a single center in a double-blind, randomized, parallel study designed to compare the efficacy and safety of single oral doses of ketoprofen (50 and 150 mg), an acetaminophen (650 mg) plus codeine (60 mg) combination, and placebo. From 1 through 4 hours after administration of the study drugs, the mean summed pain intensity difference (SPID) and time-weighted total pain relief (TOPAR) scores for the three active treatments generally were significantly (P less than 0.05) higher than those for placebo but not significantly different from each other. At the 6-hour evaluation, the ketoprofen groups, but not the acetaminophen-codeine group, had higher (P less than 0.05) mean SPID and TOPAR scores than the placebo group, as a result of a shorter duration of pain relief in the acetaminophen-codeine group. The 6-hour TOPAR scores were significantly (P less than 0.05) higher for both ketoprofen groups than for the acetaminophen-codeine group; the ketoprofen 150 mg group also had significantly (P less than 0.05) higher mean 6-hour SPID and global subjective assessment scores. As a result of a higher frequency of somnolence, there was a significantly (P less than 0.05) greater incidence of central nervous system adverse drug reactions among patients treated with acetaminophen plus codeine than among those treated with 150 mg of ketoprofen. These results indicate that the analgesic efficacy of both 50 and 150 mg doses of ketoprofen equals that of acetaminophen 650 mg plus codeine 60 mg and the duration of the analgesic effect of ketoprofen is significantly longer." ]	This update confirms previous findings that combining paracetamol with codeine provided clinically useful levels of pain relief in about 50% of patients with moderate to severe postoperative pain, compared with under 20% with placebo. New information for remedication shows that the combination extended the duration of analgesia by about one hour compared to treatment with the same dose of paracetamol alone. At higher doses, more participants experienced adequate pain relief, but the amount of information available for the 1000 mg paracetamol plus 60 mg codeine dose was small, and based on limited information.
CD000410	[ "17681325", "18583332", "16873892", "10599545", "19834718", "7962373", "8458463", "15900367", "11172835", "18345521", "8530644", "1555691" ]	[ "Effectiveness of highly purified human menopausal gonadotropin vs. recombinant follicle-stimulating hormone in first-cycle in vitro fertilization-intracytoplasmic sperm injection patients.", "Highly purified hMG versus recombinant FSH in ovarian hyperstimulation with GnRH antagonists--a randomized study.", "Clinical outcome following stimulation with highly purified hMG or recombinant FSH in patients undergoing IVF: a randomized assessor-blind controlled trial.", "Good results of milder form of ovarian stimulation in an in vitro fertilization/intracytoplasmic sperm injection program.", "Comparison of mild stimulation and conventional stimulation in ART outcome.", "A randomized prospective study of gonadotrophin with or without gonadotrophin-releasing hormone agonist for treatment of unexplained infertility.", "Comparison of short 7-day and prolonged treatment with gonadotropin-releasing hormone agonist desensitization for controlled ovarian hyperstimulation.", "Evaluation of ovulation induction protocols for poor responders undergoing assisted reproduction techniques.", "Impact of recombinant follicle-stimulating hormone and human menopausal gonadotropins on in vitro fertilization outcome.", "Comparison of GnRH agonists and antagonists in normoresponder IVF/ICSI in Turkish female patients.", "Induction of pre-ovulatory gonadotrophin surge with gonadotrophin-releasing hormone agonist compared to pre-ovulatory injection of human chorionic gonadotrophins for ovulation induction in intrauterine insemination treatment cycles.", "The routine use of gonadotropin-releasing hormone agonists for all patients undergoing in vitro fertilization. Is there any medical advantage? A prospective randomized study." ]	[ "To compare the effectiveness of highly purified hMG with recombinant FSH (rFSH) in IVF-intracytoplasmic sperm injection patients who were treated with a GnRH agonist.\n An open-label, prospective, randomized comparison of fixed gonadotropin regimens.\n Eighteen Dutch IVF centers.\n Six hundred twenty-nine patients who were selected for IVF-intracytoplasmic sperm injection.\n Patients were randomized to receive either highly purified hMG or rFSH in a fixed dosage of 150 IU/d after GnRH-agonist suppression (long protocol).\n Ongoing pregnancy rate per started cycle. Difference between the two treatment groups was tested by using odds ratios, including the 95% confidence limits (intention-to-treat sample), and by using the Fisher's exact test (per-protocol sample).\n The ongoing pregnancy rates per started cycle were 26.3% and 25.2% for highly purified hMG and rFSH, respectively (no statistically significant difference). Treatment with highly purified hMG resulted in statistically significantly fewer oocytes (n = 7.8) than did treatment with rFSH (n = 10.6). There were no differences with respect to fertilization rates and implantation rates. Cycles with highly purified hMG were statistically significantly less often canceled as a result of ovarian hyperresponse (2.0% vs. 6.0% for highly purified hMG and rFSH, respectively).\n Compared with rFSH, highly purified hMG did not result in superiority in ongoing pregnancy rates in first-cycle IVF-intracytoplasmic sperm injection patients who were treated with a fixed dosage of 150 IU of gonadotropin per day. Compared with rFSH, treatment with highly purified hMG resulted in retrieval of fewer oocytes, a lower incidence of hyperresponse, and comparable pregnancy rates.", "Highly purified hMG (hp-hMG) has recently shown better cycle outcome than the recombinant FSH (rFSH) when compared in GnRH agonist long protocol cycles. However, they have not yet been compared in GnRH antagonist cycles.\n A RCT comparing the ongoing pregnancy rate (primary end-point) in 280 patients undergoing IVF/ICSI after stimulation with hp-hMG or rFSH controlled with a GnRH antagonist.\n No significant differences were observed between hp-hMG and rFSH in terms of the ongoing pregnancy rate per started cycle (35.0 versus 32.1%, respectively; P = 0.61); relative risk: 1.09 (95% confidence interval: 0.78-1.51; risk difference: 2.9%). No differences were observed for implantation, clinical pregnancy and pregnancy loss rates. More oocytes were obtained from patients receiving rFSH then hMG (14.4 +/- 8.1 versus 11.3 +/- 6.0, respectively; P = 0.001). Estradiol was higher at the end of stimulation in the hp-hMG group (P = 0.02), whereas progesterone was higher in patients stimulated with rFSH (P < 0.001).\n A similar outcome was observed for hp-hMG and rFSH when used for stimulation in GnRH antagonist cycles. However, some differences were found in ovarian response in terms of oocyte yield and hormonal profile. Clinical Trials.gov Trial registration number: NCT00669786.", "LH activity may influence treatment response and outcome in IVF cycles.\n A randomized, assessor-blind, multinational trial compared ongoing pregnancy rates (primary end-point) in 731 women undergoing IVF after stimulation with highly purified menotrophin (HP-hMG) (n = 363) or recombinant FSH (rFSH) (n = 368) following a long GnRH agonist protocol. Patients received identical pre- and post-randomization interventions. One or two embryos were transferred on day 3.\n More oocytes were retrieved (P < 0.001) after rFSH treatment (11.8) compared with HP-hMG treatment (10.0), but a higher proportion developed into top-quality embryos (P = 0.044) with HP-hMG (11.3%) than with rFSH (9.0%). At the end of stimulation, lower estradiol (E(2)) (P = 0.031) and higher progesterone (P < 0.001) levels were found with rFSH, even after adjusting for follicular response. The distribution of hypo-, iso- and hyper-echogenic endometrium showed a significant (P = 0.023) shift towards the hyperechogenic pattern after rFSH treatment. The ongoing pregnancy rate per cycle was 27% with HP-hMG and 22% with rFSH [odds ratio (95% confidence interval): 1.25 (0.89-1.75)].\n Superiority of HP-hMG over rFSH in ongoing pregnancy rate could not be concluded from this study, but non-inferiority was established. Pharmacodynamic differences in follicular development, oocyte/embryo quality, endocrine response and endometrial echogenicity exist between HP-hMG and rFSH preparations, which may be relevant for treatment outcome.", "In a prospective study, we compared two protocols of ovulation stimulation, the clomiphene citrate and human menopausal gonadotropin (hMG) versus D-triptorelin, a long-acting gonadotropin-releasing hormone (GnRH) agonist and hMG in 324 couples having their first in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) program, in terms of pregnancy rates and cost-effectiveness of drugs used. The GnRH agonist/hMG group was characterized by a greater mean number of ampoules of hMG used (31.7 versus 10.2), a larger number of oocytes collected (10.4 versus 4.2), and a larger number of embryos obtained (5.8 versus 2.9). With the policy of transferring only two of the best quality embryos, the mean number of embryos replaced were comparable (1.8 in clomiphene citrate/hMG and 1.9 in GnRH agonist/hMG group). The percentage of patients reaching embryo transfer was lower in the clomiphene citrate/hMG than in the GnRH agonist/hMG group (84.1% versus 93.1%, respectively). However, the combined results of the IVF and ICSI procedure in terms of pregnancy rate, both per patient and per embryo transfer were better, though not significantly in the clomiphene citrate/hMG than in GnRH agonist/hMG group (25.0% and 29.7% versus 23.7% and 25.5%, respectively). Similarly, the implantation rate was better (19.0% versus 13.5%, respectively). With the use of clomiphene citrate/hMG, a fivefold less costly drug regimen, we obtained pregnancy rates equivalent to those gained using GnRH agonist/hMG in our IVF/ICSI program.", "To provide a treatment for particular condition that is the most effective treatment with the least risk and cost for the patient we compared the efficacy of using clomiphene 100 mg + delayed low dose gonadotropin + flexible GnRH antagonist administration for ovarian stimulation protocol and GnRH agonist + gonadotropin for stimulation protocol in IVF outcome.\n Clinical outcome of 243 women with regularly menstruation who were candidate for IVF. They had undergone stimulation with GnRH agonist and gonadotropin (group A) or clomiphene citrate, gonadotropin and GnRH antagonist (group B). Main outcome was ongoing pregnancy.\n There were no significant difference in mean age, cause of infertility, basal FSH, BMI, duration of infertility, endometrial thickness on the day HCG administration in two groups. The number of recovered oocytes, obtained embryos, transferred embryos, peak of estradiol on the day HCG administration and OHSS were significantly higher in group A. Significantly more patients in control group had embryos for cryopreservation. There were no significant difference in clinical pregnancy rate and ongoing pregnancy rate between two groups.\n Clomiphene + delayed low dose gonadotropin + flexible GnRH - antagonist stimulation is an acceptable alternative protocol for IVF in patients with regularly menstruation.", "The use of gonadotrophin-releasing hormone agonist (GnRHa) in combination with human menopausal gonadotrophin (HMG) for ovulation induction has been advocated for the treatment, particularly by in-vitro fertilization (IVF) of various types of infertility. The present study was designed to compare the clinical efficacy of HMG alone with a short protocol of GnRHa/HMG for treatment of unexplained infertility. A total of 91 couples with unexplained infertility were randomly assigned to one of two treatments; either HMG with intra-uterine insemination (IUI) (45 patients, 62 cycles) or GnRHa/HMG with IUI (46 patients, 69 cycles) treatments. Progesterone concentrations on the day of human chorionic gonadotrophin (HCG) administration were significantly higher in HMG (1.5 +/- 0.9 ng/ml) versus GnRHa/HMG (0.8 +/- 0.6 ng/ml; P < 0.05) cycles. Furthermore, GnRHa suppressed the occurrences of premature luteinization (GnRHa/HMG 5.8% and HMG 24.2% respectively). However, there were no significant differences in HMG dose requirements, plasma oestradiol concentrations or follicular development on the day of HCG administration between the two groups. Nor were any significant differences found in the pregnancy rates between the two treatment protocols (GnRHa/HMG 13.0% and HMG 11.3% respectively). Our results suggest no beneficial effect of GnRHa/HMG compared to HMG alone for the treatment of unexplained infertility, based on pregnancy rates.", "To compare two treatment regimens associating a gonadotropin-releasing hormone agonist (GnRH-a) and human menopausal gonadotropin (hMG) for controlled ovarian hyperstimulation (COH).\n A prospective randomized trial.\n The outpatient fertility clinic of a university tertiary care center, the Hôpital A. Béclère, Clamart, France.\n One hundred eighty-two in vitro fertilization (IVF) candidates undergoing new or repeat IVF cycles at Hôpital A. Béclère over a 4-month period.\n Group 1 (7-day protocol): A short-acting preparation of GnRH-a (Tripteriline 0.1) was administered daily for 7 days, starting on cycle day 2. Ovarian stimulation with hMG was started on cycle day 4. Group 2 (long protocol): A timed release preparation of GnRH-a (Tripteriline 3.75 mg) was administered on cycle day 2. Ovarian stimulation with hMG was started after documented ovarian suppression.\n Response to COH, pregnancy rate (PR), tolerance.\n In the 7-day protocol, the amount of hMG required was markedly lower at 24 +/- 7 than in the long protocol group requiring 42.5 +/- 9.75 vials (75 IU) (mean +/- SD). No elevation of plasma LH occurred in either group. The number of oocytes retrieved was 7.3 +/- 1 and 10.7 +/- 1.2 (mean +/- SD) in the 7-day and long protocols, respectively. Yet, the number of embryos obtained and the PRs were similar in the two treatment groups.\n We observed that in COH, GnRH-a treatment could be interrupted safely several days before human chorionic gonadotropin administration without risking a premature increase of plasma luteinizing hormone. Moreover, the number of embryos available for fresh transfer and the ongoing PRs were similar in the new 7-day and in the classic long GnRH-a/hMG protocols, despite the smaller number of oocytes suggesting a greater efficiency of the 7-day protocol. The peak estradiol level and the hMG requirement were also lower in the 7-day GnRH-a/hMG protocol.", "To compare 3 stimulation protocols in poor ovulation responders undergoing in-vitro fertilization (IVF).\n The study was a randomized, prospective clinical trial from June 2003 to July 2004, in Royan Institute, Tehran, Iran. One hundred and fifty-four patients, who had poor responses to ovulation induction in at least one previous IVF attempt, were randomly divided into 3 groups. In the first group, human menopausal gonadotropin (HMG) was administered from day 3 of the cycle at a dose rate of 150 IU/day. In the second group, gonadotropin-releasing hormone (GnRH) agonist was started at a dose rate of 800 microg/day by nasal spray or 500 microg/day subcutaneously in the mid-luteal phase, followed by a standard HMG dose after pituitary down regulation was confirmed. In the third group, clomiphene at a dose rate of 100 mg/day was given from day 3 and HMG from day 6. Our main outcomes were number of mature oocytes, cancellation rate, number of HMG ampoules used and incidence premature luteinizing hormone (LH) surge.\n There was a high incidence of premature LH surge in all groups except in the GnRH group (p=0.0001) and there were significant differences between groups in HMG requirements (p=0.004). There were no significant differences between groups in number of mature oocytes recovered and cancellation rate.\n Results showed no advantage in the use of GnRH agonist compared to the older regimens of clomiphene plus HMG and HMG alone. The cancellation rate was similar for 3 protocols and HMG requirement was higher with the use of GnRH agonist. The treatment of poor responders in assisted reproductive technologies remains a challenge.", "To investigate possible differences between using recombinant FSH (rFSH) and hMG for ovarian stimulation in IVF/intracytoplasmic sperm injection (ICSI) cycles.\n Parallel group design. Prospective, randomized clinical study.\n A tertiary care infertility clinic.\n A total of 578 patients of our IVF/ICSI routine were recruited.\n Treatment with hMG was used for 282 patients (282 cycles), whereas 296 patients (296 cycles) were treated with rFSH. The number of cycles leading to an embryo transfer were 248 and 259, respectively.\n Primary: clinical pregnancy rate. Secondary: treatment days, total dose of gonadotropin administered, number of oocytes retrieved, number of mature oocytes, and embryo quality.\n Of the cycles with embryo transfer, the pregnancy rates were 30.1% and 32.3% in the rFSH and the hMG groups, respectively. This difference is not statistically significant (P=0.798). Treatment with rFSH resulted in a significantly higher number of recovered oocytes compared with the hMG group but was also associated with a higher number of ampoules needed to reach the criterion for hCG administration. No significant differences were found with regard to the number of mature oocytes, the number of treatment days, and the embryo quality.\n In terms of the clinical pregnancy rate, no significant differences between the two stimulation regimens can be stated.", "To evaluate the results of gonadotropin-releasing hormone agonist (GnRHa) and gonadotropin-releasing hormone antagonist (GnRHant) use in two demographically matched groups of normoresponder in-vitro fertilisation or intracytoplasmic sperm injection (IVF/ICSI) patients in a prospective study.\n We randomised 93 patients undergoing IVF/ICSI between May 2005 and August 2006. Patients with IVF indications were included except for those with polycystic ovary syndrome or azoospermia, women older than 38 years and those with follicle-stimulating hormone (FSH) > or =10 IU/ml. Patients were stimulated with standard 225 IU recombinant FSH. In Group I (n=45) a daily dose of GnRHant cetrorelix acetate 0.25 mg was administered when follicles reached a diameter of > or =14 mm. Group II (n=48) patients were desensitised with the GnRHa, leuprolide acetate, in a long protocol. Human chorionic gonadotropin (hCG) was administered when at least three follicles of 18 mm in diameter were observed. Oocyte retrieval was scheduled 36 hours following hCG administration and embryos were transferred on day 3 after oocyte retrieval.\n The two groups were homogenous for age, infertility duration, basal FSH and serum oestradiol (E2) (P=0.537, P=0.911, P=0.103 and P=0.733, respectively). In Group II (the GnRHa group) more antral follicles (P<0.001), a longer induction duration (P=0.017) and higher peak E2 levels (P<0.001) were observed. No differences were observed in the number of oocytes retrieved (P=0.749), embryos achieved and transferred (P=0.677), or fertilisation rates (P=0.839) between the two groups. There was no statistically significant difference between groups in clinical pregnancy rates, cycle cancellation and ovarian hyperstimulation (P=0.437, P=0.109 and P=0.415, respectively).\n GnRHant and GnRHa provide comparable results in normoresponder patients, while GnRHant allows a greater flexibility in their treatment.", "The clinical outcome of intrauterine insemination (IUI) treatment cycles employing a gonadotrophin-releasing hormone agonist [GnRHa, triptorelin (Decapeptyl)] or human chorionic gonadotrophin (HCG) for ovulation induction was compared. A group of 48 patients presenting with amenorrhoea, oligomenorrhoea or unexplained infertility were all treated with human menopausal gonadotrophins (HMG) from day 5 of the cycle, on an individualized schedule. They were then randomly divided into two groups to receive either a single s.c. injection of 0.1 mg triptorelin or a single i.m. injection of 10,000 IU HCG after follicular maturation. IUI was performed approximately 24 and 48 h following the injection. A transitory increase in serum luteinizing hormone and follicle stimulating hormone concentrations was achieved following injection of GnRHa. A total of 24 patients received 72 treatment cycles with GnRHa, producing 11 conceptions (15.3%) and two abortions (18.2%), resulting in a term pregnancy rate of 13.6%. There were four cases of grade 3-4 ovarian hyperstimulation syndrome (OHSS), two of which were conception cycles. In all, 24 patients underwent 68 cycles treated with HCG, producing 18 conceptions (26.5%) and six abortions (33.3%), resulting in a term pregnancy rate of 19.0%. There were eight cycles of grade 3-4 OHSS, two of which were conception cycles. These results show that an s.c. injection of a relatively low dose of GnRHa can be as effective as HCG in producing pregnancy in IUI treatment cycles.", "To determine if the routine use of gonadotropin-releasing hormone agonists (GnRH-a) for all patients undergoing in vitro fertilization (IVF) produces any significant medical advantage.\n Prospective randomized study.\n Three hundred eight patients having their first ever IVF attempt.\n Patients were randomly divided into four groups and received either human menopausal gonadotropin (hMG) alone for ovarian simulation (group A, n = 81); clomiphene citrate and hMG (group B, n = 77); a 3-day ultrashort course of GnRH-a and hMG (group C, n = 74); or pituitary desensitization with GnRH-a followed by hMG (group D, n = 76).\n The indications for IVF and mean age of all four groups of patients were comparable. There was a significant difference in the number of embryos cleaved and transferred among the groups, but there were no significant differences in the cancellation rate, mean number of oocytes collected or fertilized, and number of cases of failed fertilization. There were also no significant differences in the pregnancy and live birth rates per cycle commenced or per embryo transfer.\n The routine use of GnRH-a for all patients undergoing IVF has practical but no significant medical advantages." ]	Although 14 RCTs were included in this review, few dealt with the same comparisons, all were small to moderate size and their methodological quality was generally poor. Any conclusions, therefore, remain tentative as they are based on a limited amount of data and will require further RCTs to substantiate them. In none of the comparisons was there a significant improvement in pregnancy rate but this may be due to the lack of power (i.e. insufficient patients randomised to demonstrate a significant difference between treatments). There was a trend towards better pregnancy rates with the addition of a GnRH-a to gonadotrophin stimulation and these interventions warrant further study. Despite theoretical advantages, urinary-derived FSH preparations did not improve pregnancy rates when compared to traditional and cheaper hMG preparations; their only demonstrable benefit was a reduced risk of OHSS in cycles when administered without the concomitant use of a GnRH-a. No conclusions can be drawn on miscarriage and multiple pregnancy rates due to insufficient reporting of these outcomes in the trials.
CD007142	[ "8894955", "1602030", "8559866", "12464834", "19573478", "1758944", "8409351", "2404539", "11086269", "8970662" ]	[ "Controlled trial of a brief cognitive-behavioural intervention in adolescent patients with depressive disorders.", "Relaxation therapy as an adjunct in radiation oncology.", "Cognitive behavior therapy, relaxation training, and tricyclic antidepressant medication in the treatment of depression.", "Relaxation and imagery for anxiety and depression control in community patients with advanced cancer.", "The DEMO trial: a randomized, parallel-group, observer-blinded clinical trial of strength versus aerobic versus relaxation training for patients with mild to moderate depression.", "Relaxation behavior therapy as sole treatment for mild hypertension.", "An exploratory study of the effectiveness of a relaxation with guided imagery protocol.", "Treatment of depressed in-patients. Cognitive therapy plus medication, relaxation plus medication, and medication alone.", "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.", "Massage and relaxation therapies' effects on depressed adolescent mothers." ]	[ "Fifty-three child and adolescent psychiatric patients with depressive disorders were randomly allocated to brief cognitive-behaviour therapy (CBT) or to a control treatment, relaxation training. Forty-eight patients completed the treatment phase of the trial, which comprised 5-8 treatment sessions. Post-treatment assessments showed a clear advantage of CBT over relaxation on measures of both depression and overall outcome. However, there were no significant differences between the treatments on comorbid anxiety and conduct symptoms. At follow-up, the differences between the groups were reduced, partly because of a high relapse rate in the DTP group and partly because subjects in the relaxation group continued to recover.", "Stress, anxiety, and depression in patients who are undergoing treatment of cancer significantly compromise the quality of their lives. The impact of stress reduction by relaxation training and imagery was studied in 82 out-patients who were undergoing curative (73 patients) or palliative (9 patients) radiotherapy. Fifty-two females and 30 males were assigned randomly to a relaxation training condition (34 patients) as an adjunct to radiation or a control condition (29 patients), which entailed education and counseling along with the RT. Using pre- and posttests of the Profile of Mood States, significant (p less than .01) reductions were noted in the treatment group in tension, depression, anger, and fatigue. The results suggest that relaxation training substantially improves several psychological parameters associated with quality of life in ambulatory patients who are undergoing radiation therapy.", "Outcomes of seven treatment trials comparing cognitive behavioral therapy to treatment with tricyclic antidepressant medication in major depressive disorder have been quite similar to one another. This led us to question whether treatment outcome in time-limited studies reflected a unique effect of cognitive behavioral therapy. To test the uniqueness hypothesis, relaxation training, a nonpharmacologic, noncognitive treatment, was chosen as a comparison for cognitive behavioral therapy as well as drug therapy. Treatment duration was 16 weeks. The sample of 37 patients treated for major depressive disorder was less depressed than those previously studied. For both cognitive behavioral therapy and relaxation training, outcome of depression was superior to that of tricyclic antidepressant medication by endpoint analysis. The posttreatment scores on the Beck Depression Inventory of 82% of the group receiving cognitive behavioral therapy improved to a Beck Depression Inventory score < or = 9 which was not significantly greater than that for the group receiving relaxation training (73%), so a unique effect was not demonstrated for cognitive behavioral therapy. The outcome for tricyclic antidepressant medication (29% improved to criteria) was significantly worse than that for cognitive behavioral therapy. The patient's pretreatment initial expectancy was not predictive.", "A community-based nursing study was conducted in Sydney, Australia, to compare the effects of progressive muscle relaxation and guided imagery on anxiety, depression, and quality of life in people with advanced cancer. In this study, 56 people with advanced cancer who were experiencing anxiety and depression were randomly assigned to 1 of 4 treatment conditions: (1) progressive muscle relaxation training, (2) guided imagery training, (3) both of these treatments, and (4) control group. Subjects were tested before and after learning muscle relaxation and guided imagery techniques for anxiety, depression, and quality of life using the Hospital Anxiety and Depression scale and the Functional Living Index-Cancer scale. There was no significant improvement for anxiety; however, significant positive changes occurred for depression and quality of life.", "To assess the benefit and harm of exercise training in adults with clinical depression.\n The DEMO trial is a randomized pragmatic trial for patients with unipolar depression conducted from January 2005 through July 2007. Patients were referred from general practitioners or psychiatrists and were eligible if they fulfilled the International Classification of Diseases, Tenth Revision, criteria for unipolar depression and were aged between 18 and 55 years. Patients (N = 165) were allocated to supervised strength, aerobic, or relaxation training during a 4-month period. The primary outcome measure was the 17-item Hamilton Rating Scale for Depression (HAM-D(17)), the secondary outcome measure was the percentage of days absent from work during the last 10 working days, and the tertiary outcome measure was effect on cognitive abilities.\n At 4 months, the strength measured by 1 repetition maximum for chest press increased by a mean (95% CI) of 4.0 kg (0.8 to 7.2; p = .014) in the strength training group versus the relaxation group, and maximal oxygen uptake increased by 2.7 mL/kg/min (1.2 to 4.3; p = .001) in the aerobic group versus the relaxation group. At 4 months, the mean change in HAM-D(17) score was -1.3 (-3.7 to 1.2; p = .3) and 0.4 (-2.0 to 2.9; p = .3) for the strength and aerobic groups versus the relaxation group. At 12 months, the mean differences in HAM-D(17) score were -0.2 (-2.7 to 2.3; p = .8) and 0.6 (-1.9 to 3.1; p = .6) for the strength and aerobic groups versus the relaxation group. At 12 months, the mean differences in absence from work were -12.1% (-21.1% to -3.1%; p = .009) and -2.7% (-11.7% to 6.2%; p = .5) for the strength and aerobic groups versus the relaxation group. No statistically significant effect on cognitive abilities was found.\n Our findings do not support a biologically mediated effect of exercise on symptom severity in depressed patients, but they do support a beneficial effect of strength training on work capacity.\n (ClinicalTrials.gov) Identifier: NCT00103415.\n Copyright 2009 Physicians Postgraduate Press, Inc.", "This study tested the efficacy of relaxation therapy as sole treatment for mild hypertension in 110 men and women recruited from a five-stage worksite blood pressure screening program. Participants were randomized to 12-weeks of relaxation therapy or support therapy. Outcome blood pressure assessments made by assessors who were unaware of group allocation revealed similar decreases in both treatment groups at post-treatment and 6-month follow-up. While body weight did not change, alcohol consumption decreased similarly in both groups, and alcohol consumption was positively correlated with both absolute diastolic blood pressure and change in diastolic blood pressure at outcome. In conclusion, a superior blood pressure effect was not associated with relaxation therapy; however, alcohol consumption decreased in both treatment groups, suggesting that both interventions facilitated changes in health risk behaviors and indirectly on blood pressure level.", "An exploratory study was done to examine the effectiveness of a relaxation with guided imagery protocol in reducing anxiety and depression and increasing self-esteem in new mothers during the first 4 weeks postpartum. The results indicate that anxiety and depression declined and self-esteem increased in subjects in both the experimental and control groups over the 4-week period. However, the decline in anxiety and the increase in self-esteem was greater in the experimental group than in the control group. The decline in depression was about the same in both groups. Further study, using more precise methodology and instrumentation, needs to be done to verify the results.", "Thirty in-patients received one of three treatments - medication (nortriptyline) alone (MA), relaxation therapy plus medication (RT&M), or cognitive therapy plus medication (CT&M) (each n = 10) - along with ward milieu. The relaxation and cognitive therapy groups participated in 12 therapy sessions. Symptoms of depression and related cognitive variables were assessed at sessions 1, 6 and 12, and at discharge. All groups improved over the course of the study. CT&M and RT&M groups reported significantly fewer depressive symptoms and negative cognitions at discharge than the MA group. The number of subjects judged depressed at discharge was lower in the CT&M group than in the MA and RT&M groups. It is proposed that a consistent rationale for treatment is a significant facilitating factor in achieving behavioural and cognitive changes in depression.", "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", "Thirty-two depressed adolescent mothers received ten 30-minute sessions of massage therapy or relaxation therapy over a five-week period. Subjects were randomly assigned to each group. Although both groups reported lower anxiety following their first and last therapy sessions, only the massage therapy group showed behavioral and stress hormone changes including a decrease in anxious behavior, pulse, and salivary cortisol levels. A decrease in urine cortisol levels suggested lower stress following the five-week period for the massage therapy group." ]	Relaxation techniques were more effective at reducing self-rated depressive symptoms than no or minimal treatment. However, they were not as effective as psychological treatment. Data on clinician-rated depressive symptoms were less conclusive. Further research is required to investigate the possibility of relaxation being used as a first-line treatment in a stepped care approach to managing depression, especially in younger populations and populations with subthreshold or first episodes of depression.
CD006649	[ "19121589", "10717252", "12232452", "15159264", "10823256", "20598077", "12706636", "12669122", "9821025", "10436448", "12174922", "19299272", "15878544", "1346817", "2556484", "15342210" ]	[ "A randomised open-label trial comparing long-term sub-cutaneous low-molecular-weight heparin compared with oral-anticoagulant therapy in the treatment of deep venous thrombosis.", "Effect of low molecular weight heparin (Certoparin) versus unfractionated heparin on cancer survival following breast and pelvic cancer surgery: A prospective randomized double-blind trial.", "Low-molecular-weight heparin versus unfractionated heparin in the treatment of patients with acute pulmonary thromboembolism.", "Subcutaneous adjusted-dose unfractionated heparin vs fixed-dose low-molecular-weight heparin in the initial treatment of venous thromboembolism.", "Fixed-dose, body weight-independent subcutaneous LMW heparin versus adjusted dose unfractionated intravenous heparin in the initial treatment of proximal venous thrombosis. EASTERN Investigators.", "PRODIGE: a randomized placebo-controlled trial of dalteparin low-molecular-weight heparin thromboprophylaxis in patients with newly diagnosed malignant glioma.", "An open-label randomized controlled trial of low molecular weight heparin compared to heparin and coumadin for the treatment of venous thromboembolic events in children: the REVIVE trial.", "Low-molecular-weight heparin in the acute and long-term treatment of deep vein thrombosis.", "Efficacy of a low molecular weight heparin administered intravenously or subcutaneously in comparison with intravenous unfractionated heparin in the treatment of deep venous thrombosis. Certoparin-Study Group.", "Venographic comparison of subcutaneous low-molecular weight heparin with oral anticoagulant therapy in the long-term treatment of deep venous thrombosis.", "Cyclophosphamide, methotrexate and fluorouracil (CMF) versus hormonal ablation with leuprorelin acetate as adjuvant treatment of node-positive, premenopausal breast cancer patients: preliminary results of the TABLE-study (Takeda Adjuvant Breast cancer study with Leuprorelin Acetate).", "A comparison of low-molecular-weight heparin and combined therapy of low-molecular-weight heparin with an anti-inflammatory agent in the treatment of superficial vein thrombosis.", "Long-term treatment of deep venous thrombosis with a low molecular weight heparin (tinzaparin): a prospective randomized trial.", "Comparison of subcutaneous low-molecular-weight heparin with intravenous standard heparin in proximal deep-vein thrombosis.", "Low molecular weight heparin (Alfa LHWH) compared with unfractionated heparin in prevention of deep-vein thrombosis after hip fractures.", "An open-label, comparative study of the efficacy and safety of once-daily dose of enoxaparin versus unfractionated heparin in the treatment of proximal lower limb deep-vein thrombosis." ]	[ "To evaluate whether low-molecular-weight heparin (LMWH) could be equally (or more) effective than oral anti-vitamin-K agents (AVK) in the long-term treatment of deep venous thrombosis (DVT).\n A randomised, open-label trial.\n In this trial, 241 patients with symptomatic proximal DVT of the lower limbs confirmed by duplex ultrasound scan were included. After initial LMWH, patients received 6 months of treatment with full therapeutic dosage of tinzaparin or acenocoumarol. The primary outcome was the 12-month incidence of symptomatic recurrent venous thrombo-embolism (VTE). Duplex scans were performed at 6 and 12 months.\n During the 12-month period, six patients (5%) of 119 who received LMWH and 13 (10.7%) of 122 who received AVK had recurrent VTE (p=0.11). In patients with cancer, recurrent VTE tended to be lower in the LMWH group (two of 36 [5.5%]) vs. seven of 33 [21.2%]; p=0.06). One major bleeding occurred in the LMWH group and three in the AVK group. Venous re-canalisation increased significantly at 6 months (73.1% vs. 47.5%) and at 12 months (91.5% vs. 69.2%) in the LMWH group.\n Tinzaparin was more effective than AVK in achieving re-canalisation of leg thrombi. Long-term tinzaparin was at least as efficacious and safe as AVK for preventing recurrent VTE, especially in patients with cancer.", "Recent studies suggest that low molecular weight heparin (LMW heparin) therapy in malignancy may improve cancer survival following surgical resection. We studied prospectively whether cancer mortality during follow-up in women with previously untreated breast, and pelvic cancer is reduced in those who randomly received LMW heparin (Certoparin) compared to patients given unfractionated heparin (UF heparin) for thrombosis prophylaxis during primary surgery. In a prospective, randomized, double-blind clinical trial, 160 patients received Certoparin and 164 UF heparin until post-operatively day 7. Survival estimations are based on the outcome data from a subset of 140 LMW heparin - and 147 UF heparin recipients. Long-term survival in the Certoparin group compared to the UF heparin group was significantly improved after 650 days (P=0. 0066) but not thereafter when analysis was performed on all cancer cell types combined. In the probability estimates survival benefit within this time was restricted to patients with pelvic cancer but was not observed in breast cancer. However, in breast cancer patients who received LMW heparin the impact of classical tumor prognostic markers was statistically significant after 1,050 days but not after 650 days. Thus, breast cancer patients with unfavorable prognosis seem to benefit in terms of survival advantage from LMW heparin within the 650 days after surgery. These results suggest that improvement in cancer survival can be achieved after even a short course of treatment with LMWH (compared to UFH) given for DVT prophylaxis in the post-operative period. An effect of UFH on disease outcome is not excluded. Further definitive trials of LMWH vs. placebo for cancer outcome (rather then DVT) using doses and schedules that may be more optimal are indicated.", "Low-molecular-weight heparin (LMWH) appears to be as effective as unfractionated heparin (UFH) for both treatment and prophylaxis of deep vein thrombosis (DVT), but limited data are available for its use in acute pulmonary thromboembolism (PTE).\n To determine whether enoxaparin, a LMWH, was clinically as efficient and safe as UFH in patients with a diagnosis of acute PTE.\n After exclusion of those with massive forms, 59 patients with acute PTE were randomly assigned to either subcutaneous enoxaparin given twice daily (1 mg/kg/dose) or adjusted dose intravenous UFH. Oral anticoagulant treatment was begun on the second day and was given for at least 6 months. We compared the treatment regimens at day 8 and day 90 with respect to a combined end point of major bleeding, recurrent venous thromboembolism (VTE), and death.\n In the first 8 days of treatment, 1 of 30 patients assigned to receive UFH (3.3%) reached one of the end points (recurrence), as compared with none of 29 patients assigned to enoxaparin. Statistically this difference was not significant (p = 0.508). By day 90, 3 patients assigned to UFH (10%) had symptomatic recurrent VTE, as compared with 1 patient assigned to enoxaparin (3.4%). There was neither major bleeding nor death in the study groups. There was an absolute difference of 6.4 percentage points between the two treatment groups, but the difference was statistically not significant (p = 0.318).\n Initial subcutaneous treatment with enoxaparin appeared to be as effective and safe as UFH in acute PTE.\n Copyright 2002 S. Karger AG, Basel", "Few reports have addressed the value of unfractionated heparin (UFH) or low-molecular-weight heparin in treating the full spectrum of patients with venous thromboembolism (VTE), including recurrent VTE and pulmonary embolism.\n In an open, multicenter clinical trial, 720 consecutive patients with acute symptomatic VTE, including 119 noncritically ill patients (16.5%) with pulmonary embolism and 102 (14.2%) with recurrent VTE, were randomly assigned to treatment with subcutaneous UFH with dose adjusted by activated partial thromboplastin time by means of a weight-based algorithm (preceded by an intravenous loading dose), or fixed-dose (adjusted only to body weight) subcutaneous nadroparin calcium. Oral anticoagulant therapy was started concomitantly and continued for at least 3 months. We recorded the incidence of major bleeding during the initial heparin treatment and that of recurrent VTE and death during 3 months of follow-up.\n Fifteen (4.2%) of the 360 patients assigned to UFH had recurrent thromboembolic events, as compared with 14 (3.9%) of the 360 patients assigned to nadroparin (absolute difference between rates, 0.3%; 95% confidence interval, -2.5% to 3.1%). Four patients assigned to UFH (1.1%) and 3 patients assigned to nadroparin (0.8%) had episodes of major bleeding (absolute difference between rates, 0.3%; 95% confidence interval, -1.2% to 1.7%). Overall mortality was 3.3% in each group.\n Subcutaneous UFH with dose adjusted by activated partial thromboplastin time by means of a weight-based algorithm is as effective and safe as fixed-dose nadroparin for the initial treatment of patients with VTE, including those with pulmonary embolism and recurrent VTE.", "Body weight-adjusted subcutaneous low-molecular-weight heparin (LMWH) has been proven to be at least as effective and safe as dose-adjusted intravenous unfractionated heparin (UFH) for the treatment of patients with venous thromboembolism. However, body weight-adjusted dosage of low-molecular-weight heparin may be cumbersome and could lead possibly to incorrect dosing. Therefore a fixed LMWH dose, independent of body-weight, might rationalize initial treatment for venous thromboembolism.\n Patients with proven proximal deep-vein thrombosis were randomly assigned to fixed dose subcutaneous LMWH Certoparin (8,000 anti-factor Xa U b.i.d.; 265 patients) or to adjusted dose i.v. UFH (273 patients) for 12 days. Vitamin K antagonists were started between day 3 and 7 and continued for up to 6 months. The primary outcome measure was a 30 percent or greater improvement in the Marder Score, as revealed by repeated venography on day 12 (end of the initial treatment). The secondary composite outcome measure included death, recurrent venous thromboembolism and major bleeding and was assessed at day 12 and after 6 months by a blinded adjunction committee.\n The Marder score improved by 30% or more in 30.3% and 25.0% of patients assigned to LMWH (198 paired venograms) and UFH (192 paired venograms), respectively (2p = 0.26). At the end of the initial treatment, the composite outcome was observed in 4 of the 265 patients (1.5%) randomized to LMWH, as compared with 14 of the 273 patients (5.1%) randomized to UFH (2p = 0.03). At 6 months these figures were 6.8% and 12.8%, respectively (risk reduction 0.53, confidence interval 0.31-0.90, 2p = 0.02).\n Fixed dose subcutaneous LMWH certoparin is at least as efficacious as UFH in resolving proximal vein thrombosis.", "Venous thromboembolism (VTE) occurs in 20-30% of patients with malignant glioma per year of survival. We tested the efficacy of long-term dalteparin low-molecular-weight heparin (LMWH) for prevention of VTE in these patients.\n Adults with newly diagnosed malignant glioma were randomized to receive dalteparin 5000 anti-Xa units or placebo, both subcutaneously once daily for 6 months starting within 4 weeks of surgery. Treatment continued for up to 12 months. The primary outcome was the cumulative risk of VTE over 6 months. The target sample size was 512 patients. Events were adjudicated by a committee unaware of treatment.\n The trial began in 2002 and closed in May 2006 because of expiration of study medication. Ninety-nine patients were randomized to LMWH and 87 to placebo. Twenty-two patients developed VTE in the first 6 months: nine in the LMWH group and 13 in the placebo group [hazard ratio (HR) = 0.51, 95% confidence interval (CI): 0.19-1.4, P = 0.29]. At 6 months, there were three major bleeds on LMWH and none on placebo; at 12 months, 5 (5.1%) major bleeds on LMWH and 1 (1.2%) on placebo occurred (HR = 4.2, 95% CI: 0.48-36, P = 0.22). All major bleeds were intracranial and occurred while on study medication. The 12-month mortality rates were 47.8% for LMWH and 45.4% for placebo (HR = 1.2, 95% CI: 0.73-2.0, P = 0.48).\n Trends suggesting reduced VTE and increased intracranial bleeding were seen in the LMWH thromboprophylaxis group. The role of long-term anticoagulant thromboprophylaxis in patients with brain tumors remains uncertain.\n © 2010 International Society on Thrombosis and Haemostasis.", "Venous thromboembolic events (VTE) are serious complications in children and for which the standard of care, unfractionated heparin followed by oral anticoagulation (UFH/OA), is problematic. The objective of REVIVE was to compare the efficacy and safety of a low molecular weight heparin (reviparin-sodium) to UFH/OA for the treatment of VTE in children.\n This multicenter, open-label study, with blinded central outcome adjudication, randomized patients with objectively confirmed VTE to receive either reviparin-sodium or UFH/OA. Dose adjustments were made using nomograms. The efficacy outcome was based on recurrent VTE and death due to VTE during the 3-month treatment period. The safety outcomes were major bleeding, minor bleeding and death. Due to slow patient accrual, REVIVE was closed prematurely.\n At 3 months, with reviparin-sodium, 2/36 patients (5.6%) had recurrent VTE or death compared to 4/40 patients (10.0%) receiving UFH/OA (odds ratio=0.53; 95% CI=(0.05, 4.00); Fisher's exact test: 2P=0.677). There were 7 major bleeds, 2/36 (5.6%) in the reviparin-sodium group and 5/40 (12.5%) in UFH/OA group (odds ratio=0.41; 95% confidence interval 0.04, 2.76); Fisher's exact test: P=0.435). There were 5 deaths during the study period, 1 (2.8%) in the reviparin-sodium group and 4 (10.0%) in the UFH/OA group. All five deaths were unrelated to VTE but one was due to an intracranial hemorrhage in the UFH/OA group.\n Although limited by small sample size, REVIVE provides valuable information on the incidence of recurrent VTE, major bleeding and problematic issues associated with therapy of VTE in children.", "Low molecular weight heparins (LMWHs) are frequently used during acute treatment of deep vein thrombosis, but their utility for long-term treatment needs to be defined. In this multi-centre trial, 378 patients with acute deep vein thrombosis were randomised to intravenous unfractionated heparin (group A), once daily subcutaneous LMWH (bemiparin) for one week (group B) or once daily bemiparin in a therapeutic dose for one week followed by a maintenance dose for 12 weeks (group C). Fifty-two per cent of patients in group A, 72% of group B and 72% of group C showed venographic reduction in thrombus size assessed objectively on day 14; 20% greater improvement in group B and C indicates not only non-inferiority of bemiparin (p = 0.00003) but also superiority (p = 0.004) compared to UFH. Day 84 venographic or Doppler sonographic recanalisation of the affected veins was demonstrated in 75.3%, 79.8% and 81.5% in groups A, B and C respectively. Mortality, recurrent thromboembolic events and bleeding were similar in the three groups. Both bemiparin regimens were more effective than UFH in reducing thrombus size during the acute phase of treatment. The efficacy in terms of recurrence of venous thromboembolism and safety of Bemiparin is similar to UFH. Bemiparin is also an effective alternative to warfarin for long-term treatment.", "The main objective of the study presented was to test if thrombus regression can be improved by treatment with an intravenously or subcutaneously administered low molecular weight heparin (LMWH). Patients with acute deep vein thrombosis were randomly assigned to receive either intravenous UFH (131 patients), intravenous (i.v.) LMWH (128 patients), or 8000 IU of the same LMWH bid subcutaneously (s.c.) (128 patients). All patients were treated with heparin for 14 to 16 days. Vitamin-K-antagonist prophylaxis was started between Day 12 and Day 14 after enrollment into the study.\n Phlebographies and perfusion/ventilation lung scans were performed at baseline and on Days 12 to 16. Primary endpoint of the study was a reduction of the phlebographic Marder score. Secondary endpoints were recurrent thrombosis and pulmonary embolism (PE), major and minor bleedings and the rate of PE at inclusion and at the end of the study assessed by ventilation/perfusion scans.\n The Marder score improved by at least 30% in 32.4% (95% CI: 22.6 ... 42.2) of the patients receiving UFH, in 34.0% (95% CI: 24.9 ... 44.0) receiving LMWH i.v. and in 42.6% (95% CI: 32.8 ... 52.8) treated with the low molecular weight heparin s.c. The difference between LMWH s.c. and UFH was 10.2% (95% CI: -3.7% ... +24.5%) (p = 0.11). PE with clinical signs confirmed by objective methods occurred in three patients of the UFH group, one of whom died and was not observed in patients of the i.v. or s.c. LMWH-groups. During the first 15 days no patient receiving UFH or i.v. LMWH, and one patient on s.c. LMWH had a recurrent thrombosis. Major bleedings were observed in four patients receiving i.v. UFH compared to nine patients on i.v. LMWH (one of these patients died) and one patient on s.c. LMWH. Perfusion ventilation lung scans were obtained from 287 patients at baseline and from 246 patients on Days 12-16. PE, defined according to PIOPED-criteria as intermediate or high probability scans, was observed in 38.0% of the patients entering the study and in 18.3% on Days 12 to 16. New asymptomatic PE occurred less frequently in the groups on LMWH (7.1%, 7.5%, respectively) than in the UFH-group (12.6%) (not significant).\n S.c. treatment with a LMWH (certoparin) (b.i.d.) is at least as effective as UFH i.v. The hypothesis of increased efficacy of subcutaneous LMWH in resolving venous thrombi will have to be confirmed by an independent study comparing s.c. LMWH with UFH. The i.v. continuous infusion of the LMWH for 12 to 16 days does not result in a higher venous re-opening rate than intravenous standard heparin.", "The primary objective of this study was to evaluate with venography the rate of thrombus regression after a fixed dose of low-molecular weight heparin (LMWH) per day for 3 months compared with oral anticoagulant therapy for deep venous thrombosis (DVT). Secondary endpoints were the comparisons of the efficacy and safety of both treatments.\n This study was designed as an open randomized clinical study in a university hospital setting. Of the 165 patients finally enrolled in the study, 85 were assigned LMWH therapy and 80 were assigned oral anticoagulant therapy. In the group randomized to oral anticoagulant therapy, the patients first underwent treatment in the hospital with standard unfractionated heparin and then coumarin for 3 months. Doses were adjusted with laboratory monitoring to maintain the international normalized ratio between 2.0 and 3.0. Patients in the LMWH group were administered subcutaneous injections of fixed doses of 40 mg enoxaparin (4000 anti-Xa units) every 12 hours for 7 days, and after discharge from the hospital, they were administered 40 mg enoxaparin once daily at fixed doses for 3 months without a laboratory control assay. A quantitative venographic score (Marder score) was used to assess the extent of the venous thrombosis, with 0 points indicating no DVT and 40 points indicating total occlusion of all deep veins. The rate of thrombus reduction was defined as the difference in quantitative venographic scores after termination of LMWH or coumarin therapy as compared with the scores obtained on the initial venographic results. The efficacy was defined as the ability to prevent symptomatic extension or recurrence of venous thromboembolism (documented with venograms or serial lung scans). The safety was defined as the occurrence of hemorrhages.\n After 3 months of treatment, the mean Marder score was significantly decreased in both groups in comparison with the baseline score, although the effect of therapy was significantly better after LMWH therapy (49.4% reduction) than after coumarin therapy (24.5% reduction; P <.001). LMWH therapy and male gender were independently associated with an enhanced resolution of the thrombus. A lower frequency of symptomatic recurrent venous thromboembolism was also shown in patients who underwent treatment with LMWH therapy (9.5%) than with oral anticoagulant therapy (23.7%; P <.05), although this difference was entirely a result of recurrence of DVT. Bleeding complications were significantly fewer in the LMWH group than in the coumarin group (1. 1% vs 10%; P <.05). This difference was caused by minor hemorrhages. Coumarin therapy and cancer were independently associated with an enhanced risk of complications. Subcutaneous heparin therapy was well tolerated by all patients.\n The patients who were allocated to undergo enoxaparin therapy had a significantly greater improvement in their quantitative venographic score, a significantly lower recurrence rate of symptomatic venous thromboembolism, and a significantly lower incidence of bleeding than patients who underwent treatment with coumarin. LMWH can be used on an outpatient basis as a safer and more effective alternative to classical oral anticoagulant therapy for the secondary prophylaxis of selected patients with DVT.", "The objective of this study was to evaluate the efficacy and tolerability of leuprorelin acetate in adjuvant treatment in comparison to standard chemotherapy with CMF in premenopausal, estrogen-receptor-positive or unknown, node-positive patients with early breast cancer.\n The patients were randomly assigned to receive either 2 years of hormone ablation with leuprorelin acetate 11.25 mg as a subcutaneous injection every three months or six courses of CMF (cyclophosphamide 500 mg/m2, methotrexate 40 mg/m2, fluorouracil 600 mg/m2, days 1 and 8, q 4 weeks). The primary study end-point was recurrence-free survival (RFS) after 2 years. Secondary end-points included overall survival, adverse events and hormonal suppression.\n Between 1995 and 1999, a total of 589 patients with breast cancer were randomized to treatment with leuprorelin acetate or CMF. The data of 227 patients were available for this first interim analysis. One hundred and ten and 117 patients were assigned to leuprorelin acetate and chemotherapy, respectively. Both treatment arms were well balanced for baseline characteristics. So far, no difference between the groups has emerged with respect to recurrence-free or overall survivaL Suppression of serum estradiol levels and menstruation was less marked in the CMF-group compared to the leuprorelin arm. The most common adverse events were low-grade hot flushes, weight gain and increased sweating in the leuprorelin-treated patients and alopecia, nausea and vomiting in the CMF-group.\n According to these preliminary results, ovarian suppression with leuprorelin acetate was as effective as standard chemotherapy for premenopausal women with hormone-sensitive, node-positive early breast cancer.", "The optimal treatment of superficial vein thrombosis (SVT) of the leg has not been determined yet. The aim of this study is to evaluate the efficacy of low-molecular-weight heparin (LMWH) as compared with combined therapy of LMWH with an anti-inflammatory agent in treatment of SVT.\n Fifty patients with SVT of the greater saphenous vein were randomly assigned to be treated with Ca-nadroparin 190 IUAxa/kg in a single dose or with same dose of Ca-nadroparin and 60 mg oral acemetacine twice daily for 10 days. The efficacy of the two treatments to relieve symptoms and signs was evaluated by using visual analogue scale.\n Significant improvements were achieved for both groups after the treatment in terms of all four symptoms (P < 0.001). Treatment scores were in favour of LMWH with anti-inflammatory agent treatment group to relieve all four symptoms. The most significant and remarkable results obtained were for the reduction of pain and local tenderness (P < 0.05). No patient experienced major complications or mortality in either group.\n The results of this study suggest that the combined therapy of LMWH with an anti-inflammatory agent is more effective than LMWH. It may be an important option in the standard treatment of SVT.", "Evaluation of the effectiveness and safety of the low molecular weight heparin (LMWH) tinzaparin versus unfractionated heparin (UFH) followed by acenocoumarol in proximal deep venous thrombosis (DVT).\n Prospective, randomized clinical trial.\n Consecutive patients (n=108) with acute leg DVT, confirmed by duplex, were randomized to either tinzaparin alone or UFH and acenocoumarol for 6 months. Patients were evaluated ultrasonographically at entry, 1, 3, 6 and 12 months. Thrombus regression, reflux distribution and the incidence of complications were studied. A cost-analysis, comparing the two treatments, was performed.\n The overall incidence of major events (mortality, DVT recurrence, pulmonary embolism, major bleeding, heparin-induced thrombocytopenia) was significantly different (p=0.035) in favor of tinzaparin (7 versus 17 events). The ultrasonographic clot volume score (an index of recanalization) decreased significantly in both treatment groups. However, tinzaparin produced significantly more extended overall recanalization from 3 months onwards (p<0.02). Thrombus regression was equivalent or in favor of tinzaparin in the different DVT subgroups and venous segments, but the statistical significance varied. Reflux showed non-significant differences overall or in subgroups. A cost-analysis resulted in favor of LMWH.\n A fixed daily dose of tinzaparin for 6 months was at least as effective and safe as UFH and acenocoumarol. Regarding major events and recanalization, there was a significant benefit in favor of tinzaparin. Long-term DVT treatment with tinzaparin could represent an alternative to conventional treatment.", "In view of the potential of low-molecular-weight heparins (LMWH) to simplify initial therapy and allow outpatient treatment of proximal deep-vein thrombosis, we undertook a randomised comparison of fixed-dose subcutaneous LMWH with adjusted-dose intravenous standard heparin in the initial treatment of this disorder. Our main objectives were to compare the efficacy of these regimens for 6 months of follow-up and to assess the risk of clinically important bleeding. Of 170 consecutive symptomatic patients with venographically proven proximal deep-venous thrombosis, 85 received standard heparin (to achieve an activated partial thromboplastin time of 1.5 to 2.0 times the pretreatment value) and 85 LMWH (adjusted only for body weight) for 10 days. Oral coumarin was started on day 7 and continued for at least 3 months. The frequency of recurrent venous thromboembolism diagnosed objectively did not differ significantly between the standard-heparin and LMWH groups (12 [14%] vs 6 [7%]; difference 7% [95% confidence interval -3% to 15%]; p = 0.13). Clinically important bleeding was infrequent in both groups (3.5% for standard heparin vs 1.1% for LMWH; p greater than 0.2). We conclude that fixed-dose subcutaneous LMWH is at least as effective and safe as intravenous adjusted-dose heparin in the initial treatment of symptomatic proximal-vein thrombosis. Since there is no need for laboratory monitoring with the LMWH regimen, patients with venous thrombosis can be treated at home.", "Efficacy and safety of a low molecular weight heparin (Alfa LMWH) was compared with unfractionated heparin (UFH) in the prevention of post-operative venous thromboembolism after hip fractures. Forty-nine patients were randomized to treatment with Alfa LMWH 7500 anti-Xa coagulometric units twice daily or with UFH 5000 IU t.i.d. Screening for thrombosis was performed with 125-I-fibrinogen leg scanning and strain-gauge plethysmography. Positive results were confirmed by venography. Five patients in the Alfa LMWH group (20 per cent) developed venographycally proven deep vein thrombosis (DVT) versus seven (29 per cent) in the UFH group. One pulmonary embolism and two deaths occurred in the UFH group and none in the LMWH group. No differences in haemorrhagic complications and blood loss indices were observed. Alfa LMWH appears to be a promising drug for prevention of venous thromboembolism after orthopaedic surgery. A \"flexible\" schedule of administration is proposed on the basis of the results of plasma anti-Xa assays.", "Treatment of deep-vein thrombosis (DVT) with a once-daily regimen of enoxaparin, rather than a continuous infusion of unfractionated heparin (UFH) is more convenient and allows for home care in some patients. This study was designed to compare the efficacy and safety of these two regimens for the treatment of patients with proximal lower limb DVT.\n 201 patients with proximal lower limb DVT from 13 centers in Brazil were randomized in an open manner to receive either enoxaparin [1.5 mg/kg subcutaneous (s.c.) OD] or intravenous (i.v.) UFH (adjusted to aPTT 1.5-2.5 times control) for 5-10 days. All patients also received warfarin (INR 2-3) for at least 3 months. The primary efficacy endpoint was recurrent DVT (confirmed by venography or ultrasonography), and safety endpoints included bleeding and serious adverse events. The rate of pulmonary embolism (PE) was also collected. Hospitalization was at the physician's discretion.\n Baseline patient characteristics were comparable between groups. The duration of hospital stay was significantly shorter with enoxaparin than with UFH (3 versus 7 days). In addition, 36% of patients receiving enoxaparin did not need to be hospitalized, whereas all of the patients receiving UFH were hospitalized. The treatment duration was slightly longer with enoxaparin (8 versus 7 days). There was a nonsignificant trend toward a reduction in the rate of recurrent DVT with enoxaparin versus UFH, and similar safety.\n A once-daily regimen of enoxaparin 1.5 mg/kg subcutaneous is at least as effective and safe as conventional treatment with a continuous intravenous infusion of UFH. However, the once daily enoxaparin regimen is easier to administer (subcutaneous versus intravenous), does not require aPTT monitoring, and leads to both a reduced number of hospital admissions and an average 4-day-shorter hospital stay." ]	LMWH is possibly superior to UFH in the initial treatment of VTE in patients with cancer. Additional trials focusing on patient important outcomes will further inform the questions addressed in this review.
CD003267	[ "14729297", "16332553", "15249521", "20219315", "17509808", "8667091", "12694632", "10640121", "9794859", "12757433", "9625213", "7603933", "16088014", "12781926", "16186262", "15249520", "15668310", "9107203", "18237352", "11129745", "8788351", "10715292", "10390003", "3977198", "18777429", "8917146", "16438813", "19060642", "12879826", "2373656", "16882375", "14528540", "8635032", "19707060", "16899964", "16708003", "17214891", "16084925", "15610326", "346537", "10723618", "6406886", "19107130" ]	[ "Promoting patient participation in consultations: a randomised controlled trial to evaluate the effectiveness of three patient-focused interventions.", "Promoting a biopsychosocial orientation in family practice: effect of two teaching programs on the knowledge and attitudes of practising primary care physicians.", "Patient-based outcome results from a cluster randomized trial of shared decision making skill development and use of risk communication aids in general practice.", "A randomized controlled trial of communication training with primary care providers to improve patient-centeredness and health risk communication.", "The effects of a shared decision-making intervention in primary care of depression: a cluster-randomized controlled trial.", "Effects of a physician communication intervention on patient care outcomes.", "Randomised controlled trial of a theoretically grounded tailored intervention to diffuse evidence-based public health practice [ISRCTN23257060].", "Diabetes care from diagnosis: effects of training in patient-centred care on beliefs, attitudes and behaviour of primary care professionals.", "Randomised controlled trial of patient centred care of diabetes in general practice: impact on current wellbeing and future disease risk. The Diabetes Care From Diagnosis Research Team.", "Educational workshop improved information-seeking skills, knowledge, attitudes and the search outcome of hospital clinicians: a randomised controlled trial.", "Improving communication skills--a randomized controlled behaviorally oriented intervention study for residents in internal medicine.", "Evaluation of a patient education leaflet designed to improve communication in medical consultations.", "Use of a consumer-led intervention to improve provider competencies.", "Increasing patient participation in reproductive health consultations: an evaluation of \"Smart Patient\" coaching in Indonesia.", "An endocrinologist-supported intervention aimed at providers improves diabetes management in a primary care site: improving primary care of African Americans with diabetes (IPCAAD) 7.", "Achieving involvement: process outcomes from a cluster randomized trial of shared decision making skill development and use of risk communication aids in general practice.", "Effects of a multidisciplinary, post-discharge continuance of care intervention on quality of life, discharge satisfaction, and hospital length of stay: a randomized controlled trial.", "The efficacy and effectiveness of process consultation in improving staff morale and absenteeism.", "Strategies for improving the quality of health care in maternal and child health in low- and middle-income countries: an overview of systematic reviews.", "Effects of a multicomponent intervention on functional outcomes and process of care in hospitalized older patients: a randomized controlled trial of Acute Care for Elders (ACE) in a community hospital.", "Empowering the patient in the consultation: a pilot study.", "Building bridges between physicians and patients: results of a pilot study examining new tools for collaborative decision making in breast cancer.", "Promoting patient participation in the cancer consultation: evaluation of a prompt sheet and coaching in question-asking.", "Expanding patient involvement in care. Effects on patient outcomes.", "Cross-cultural medical education: can patient-centered cultural competency training be effective in non-Western countries?", "Patient-initiated prevention discussions. Two interventions to stimulate patients to initiate prevention discussions.", "Involving patients in primary care consultations: assessing preferences using discrete choice experiments.", "Can nurses impact patient outcomes using a patient-centered care model?", "A cluster randomised trial to evaluate a nutrition training programme.", "Promoting parent-provider interaction during young children's health-supervision visits.", "Effective improvement of doctor-patient communication: a randomised controlled trial.", "The impact of tailored interventions on a community health center population.", "Increasing patient involvement in choosing treatment for early breast cancer.", "The tools of an evidence-based culture: implementing clinical-practice guidelines in an Israeli HMO.", "Randomised controlled trial of a collaborative care model with psychiatric consultation for persistent medically unexplained symptoms in general practice.", "Cluster randomized controlled trial of the effectiveness of audit and feedback and educational outreach on improving nursing practice and patient outcomes.", "Medical communication and technology: a video-based process study of the use of decision aids in primary care consultations.", "Can a facilitated programme promote effective multidisciplinary audit in secondary care teams? An exploratory trial.", "A practical randomized trial to improve diabetes care.", "Patient participation in the patient-provider interaction: the effects of patient question asking on the quality of interaction, satisfaction and compliance.", "Empowering older patients to communicate more effectively in the medical encounter.", "Improving drug-therapy decisions through educational outreach. A randomized controlled trial of academically based \"detailing\".", "Development and pilot evaluation of a complex intervention to improve experienced continuity of care in patients with cancer." ]	[ "The aim of this experimental study was to evaluate the effectiveness of three patient-focused interventions designed to increase patient question asking in clinical consultations. Patients were randomly allocated to one of five conditions to receive either one of three interventions or to serve as an attention control group or a control group. The primary outcome measure was question asking by the patient of their physician. Participants in the intervention groups did not ask more questions than participants in the control groups. Immediately after the consultation participants in the intervention groups had higher levels of self-efficacy in asking questions. Three months after the index visit patients in the intervention groups were significantly more likely to be satisfied to some degree than patients in the control group. There was no difference in diabetic control. These results suggest that simple brief patient-focused interventions do not change patient behaviour in medical outpatient consultations.", "The bio-psychosocial (BPS) approach to patient care has gained acceptance in medical education. However, reported teaching programs rarely describe the efficacy of alternative approaches to continuing medical education aimed at promoting a BPS approach. The objective was to describe and evaluate the effect of two teaching programs on learners' BPS knowledge, management intentions, patient-centered attitudes, professional self-esteem, burnout, work related strain and mental workload. The learners were Israeli general practitioners. The first (\"didactic\") program consisted of problem-based reading assignments, lectures and discussions. The second (\"interactive\") program consisted of reading assignments, lectures and discussions, in addition to role-playing exercises, Balint groups and one-to-one counseling by a facilitator. One month before and six months after the teaching interventions, we used structured questionnaires to test for knowledge, management intentions (responses to questions, such as \"what would you tell a patient with ...\") and attitudes. Both programs led to measurable improvement in knowledge, intentions, patient-centered attitudes and self-esteem. The interactive teaching approach improved significantly more the learners' professional self-esteem and intentions than the didactic approach. Self-reported burnout significantly increased after the program. It is concluded that teaching intervention enhanced a BPS orientation and led to changes in knowledge, intentions, self-esteem and attitudes. An interactive method of instruction was more effective in achieving some of these objectives than a didactic one. The observed increase in burnout was unexpected and requires further study and confirmation.", "Shared decision-making (SDM) between professionals and patients is increasingly advocated from ethical principles. Some data are accruing about the effects of such approaches on health or other patient-based outcomes. These effects often vary substantially between studies.\n Our aim was to evaluate the effects of training GPs in SDM, and the use of simple risk communication aids in general practice, on patient-based outcomes.\n A cluster randomized trial with crossover was carried out with the participation of 20 recently qualified GPs in urban and rural general practices in Gwent, South Wales. A total of 747 patients with known atrial fibrillation, prostatism, menorrhagia or menopausal symptoms were invited to a consultation to review their condition or treatments. After baseline, participating doctors were randomized to receive training in (i) SDM skills; or (ii) the use of simple risk communication aids, using simulated patients. The alternative training was then provided for the final study phase. Patients were randomly allocated to a consultation during baseline or intervention 1 (SDM or risk communication aids) or intervention 2 phases. A randomly selected half of the consultations took place in 'research clinics' to evaluate the effects of more time for consultations, compared with usual surgery time. Patient-based outcomes were assessed at exit from consultation and 1 month follow-up. These were: COMRADE instrument (principal measures; subscales of risk communication and confidence in decision), and a range of secondary measures (anxiety, patient enablement, intention to adhere to chosen treatment, satisfaction with decision, support in decision making and SF-12 health status measure). Multilevel modelling was carried out with outcome score as the dependent variable, and follow-up point (i.e. exit or 1 month later for each patient), patient and doctor levels of explanatory variables.\n No statistically significant changes in patient-based outcomes due to the training interventions were found: COMRADE risk communication score increased 0.7 [95% confidence interval (CI) -0.92 to 2.32] after risk communication training and 0.9 (95% CI -0.89 to 2.35) after SDM training; and COMRADE satisfaction with communication score increased by 1.0 (95% CI -1.1 to 3.1) after risk communication, and decreased by 0.6 (95% CI 2.7 to -1.5) after SDM training. Patients' confidence in the decision (2.1 increase, 95% CI 0.7-3.5, P < 0.01) and expectation to adhere to chosen treatments (0.7 increase, 95% CI 0.04-1.36, P < 0.05) were significantly greater among patients seen in the research clinics (when more time was available) compared with usual surgery time. Most outcomes deteriorated between exit and 1 month later. There was no interaction between intervention effects.\n Patients can be more involved in treatment decisions, and risks and benefits of treatment options can be explained in more detail, without adversely affecting patient-based outcomes. SDM and risk communication may be advocated from values and ethical principles even without evidence of health gain or improvement in patient-based outcomes, but the resources required to enhance these professional skills must also be taken into consideration. These data also indicate the benefits of extra consultation time.", "to determine the efficacy and effectiveness of training to improve primary care providers' patient-centered communication skills and proficiency in discussing their patients' health risks.\n twenty-eight primary care providers participated in a baseline simulated patient interaction and were subsequently randomized into intervention and control groups. Intervention providers participated in training focused on patient-centered communication about behavioral risk factors. Immediate efficacy of training was evaluated by comparing the two groups. Over the next 3 years, all providers participated in two more sets of interactions with patients. Longer term effectiveness was assessed using the interaction data collected at 6 and 18 months post-training.\n The intervention providers significantly improved in patient-centered communication and communication proficiencies immediately post-training and at both follow-up time points.\n this study suggests that the brief training produced significant and large differences in the intervention group providers which persisted 2 years after the training.\n the results of this study suggest that primary care providers can be trained to achieve and maintain gains in patient-centered communication, communication skills and discussion of adverse childhood events as root causes of chronic disease.\n 2010 Elsevier Ireland Ltd. All rights reserved.", "Patient-centred depression care approaches should better address barriers of insufficient patient information and involvement in the treatment decision process. Additional research is needed to test the effect of increased patient participation on outcomes. The aim of this study was to assess, if patient participation in decision-making via a shared decision-making intervention leads to improved treatment adherence, satisfaction, and clinical outcome without increasing consultation time.\n Cluster-randomized controlled intervention study based on physician training and patient-centered decision aid compared to usual care in primary care settings in Südbaden region of Germany. Twenty-three primary care physicians treating 405 patients with newly diagnosed depression were enrolled. Patient involvement was measured with the patient perceived involvement in care scale (PICS) and a patient participation scale (MSH-scale). Patient satisfaction was measured by the CSQ-8 questionnaire. Treatment adherence was evaluated by patient and provider self-report. Depression severity and remission outcomes were assessed with the Brief PHQ-D.\n Physician facilitation of patient participation improved significantly and to a greater extent in the intervention compared to the control group. There was no intervention effect for depression severity reduction. Doctor facilitation of patient participation, patient-rated involvement, and physician assessment of adherence improved only in the intervention group. Patient satisfaction at post-intervention was higher in the intervention group compared to the control group. The consultation time did not differ between groups.\n A shared decision-making intervention was better than usual care for improving patient participation in treatment decision-making, and patient satisfaction without increasing consultation time. Additional research is needed to model causal linkages in the decision-making process in regard to outcomes.\n The study results encourage the implementation of patient participation in primary care of depression.", "To determine whether an intervention designed to improve patient-physician communication increases the frequency with which physicians elicit patients' concerns, changes other communication behaviors, and improves health care outcomes.\n Pretest-posttest design with random assignment of physicians to intervention or control groups.\n General medicine clinics of a university-affiliated Veterans Affairs Hospital.\n Forty-two physicians and 348 continuity care patients taking prescription medications for chronic medical conditions.\n Intervention group physicians received 4.5 hours of training on eliciting and responding to patients' concerns and requests, and their patients filled out the Patient Requests for Services Questionnaire prior to a subsequent clinic visit. Control group physicians received 4.5 hours of training in medical decision-making.\n The frequency with which physicians elicited all of a patient's concerns increased in the intervention group as compared with the control group (p = .032). Patients perceptions of the amount of information received from the physician did increase significantly (p < .05), but the actual magnitude of change was small. A measure of patient satisfaction with the physicians was high at baseline and also showed no significant change after the intervention. Likewise, the intervention was not associated with changes in patient compliance with medications or appointments, nor were there any effects on outpatient utilization.\n A low-intensity intervention changed physician behavior but had no effect on patient outcomes such as satisfaction, compliance, or utilization. Interventions may need to focus on physicians and patients to have the greatest effect.", "Previous studies have shown that Norwegian public health physicians do not systematically and explicitly use scientific evidence in their practice. They work in an environment that does not encourage the integration of this information in decision-making. In this study we investigate whether a theoretically grounded tailored intervention to diffuse evidence-based public health practice increases the physicians' use of research information.\n 148 self-selected public health physicians were randomised to an intervention group (n = 73) and a control group (n = 75). The intervention group received a multifaceted intervention while the control group received a letter declaring that they had access to library services. Baseline assessments before the intervention and post-testing immediately at the end of a 1.5-year intervention period were conducted. The intervention was theoretically based and consisted of a workshop in evidence-based public health, a newsletter, access to a specially designed information service, to relevant databases, and to an electronic discussion list. The main outcome measure was behaviour as measured by the use of research in different documents.\n The intervention did not demonstrate any evidence of effects on the objective behaviour outcomes. We found, however, a statistical significant difference between the two groups for both knowledge scores: Mean difference of 0.4 (95% CI: 0.2-0.6) in the score for knowledge about EBM-resources and mean difference of 0.2 (95% CI: 0.0-0.3) in the score for conceptual knowledge of importance for critical appraisal. There were no statistical significant differences in attitude-, self-efficacy-, decision-to-adopt- or job-satisfaction scales. There were no significant differences in Cochrane library searching after controlling for baseline values and characteristics.\n Though demonstrating effect on knowledge the study failed to provide support for the hypothesis that a theory-based multifaceted intervention targeted at identified barriers will change professional behaviour.", "In a randomised trial, general practitioners and nurses in 21 practices were trained in patient-centred consulting and use of materials for people with Type 2 diabetes (GPs 0.5 days; nurses 1.5 days; two optional follow-up half-days). Twenty practices formed the comparison group. Professional beliefs, attitudes and behaviour were measured (pre-trial, close-of-course and end-of-trial), supported by patient reports of nurse behaviour (141 trained: 108 comparison patients, 1 year after diagnosis). A total of 49 practice nurses responded (29 trained; 20 comparison). Trained nurses rated relative importance of patient-centred to professional-centred care as greater than comparison nurses. Trained nurses became less keen on the approach during the trial, and perceived time constraints persisted. Patients diagnosed later in the study were less likely to recognise intervention materials. Trained nurses rated delivery of important aspects of care and satisfaction with style of care as lower than comparison nurses, but patients were more positive about delivery of care from trained than comparison nurses. Although nurses rated patient-centred care as important, whether or not they had been trained as part of the trial, the short, generalizable training programme significantly reduced nurse perceptions of their ability to deliver it. Nonetheless, patients reported that important aspects of diabetes care were delivered more if their nurses had been trained in patient-centred consulting. This raises issues concerning measurement scales completed by trained professionals.", "To assess the effect of additional training of practice nurses and general practitioners in patient centred care on the lifestyle and psychological and physiological status of patients with newly diagnosed type 2 diabetes.\n Pragmatic parallel group design, with randomisation between practice teams to routine care (comparison group) or routine care plus additional training (intervention group); analysis at one year, allowing for practice effects and stratifiers; self reporting by patients on communication with practitioners, satisfaction with treatment, style of care, and lifestyle.\n 41 practices (21 in intervention group, 20 in comparison group) in a health region in southern England.\n 250/360 patients (aged 30-70 years) diagnosed with type 2 diabetes and completing follow up at one year (142 in intervention group, 108 in comparison group).\n 1.5 days' group training for the doctors and nurses-introducing evidence for and skills of patient centred care and a patient held booklet encouraging questions.\n Quality of life, wellbeing, haemoglobin A1c and lipid concentrations, blood pressure, body mass index (kg/m2).\n Compared with patients in the C group, those in the intervention group reported better communication with the doctors (odds ratio 2.8; 95% confidence interval 1.8 to 4.3) and greater treatment satisfaction (1.6; 1.1 to 2.5) and wellbeing (difference in means (d) 2.8; 0.4 to 5.2). However, their body mass index was significantly higher (d=2.0; 0.3 to 3.8), as were triglyceride concentrations (d=0.4 mmol/l; 0.07 to 0.73 mmol/l), whereas knowledge scores were lower (d=-2.74; -0.23 to -5.25). Differences in lifestyle and glycaemic control were not significant.\n The findings suggest greater attention to the consultation process than to preventive care among trained practitioners; those committed to achieving the benefits of patient centred consulting should not lose the focus on disease management.", "A double-blind randomised controlled trial was conducted on a group of Hong Kong hospital clinicians. The objective was to test if a three-hour educational workshop (with supervised hands-on practice) is more effective (than no training) to improve clinical question formulation, information-seeking skills, knowledge, attitudes, and search outcomes. The design was a post-test-only control group; recruitment by stratified randomization (by profession), blocked at 800. End-user training was more effective than no training in improving clinical question formulation, in raising awareness, knowledge, confidence and use of databases, but had made no impact on preference for secondary databases. It changed the attitude of clinicians to become more positive towards the use of electronic information services (EIS). Participants had higher search performance and outcomes (satisfaction with information obtained (NNT = 3), EIS satisfaction (NNT = 3) and success in problem solving (NNT = 4)). The workshop improved knowledge and skills in evidence-based searching, but this effect gradually eroded with time. Search logs confirmed that follow-up is required if effects are to be sustained. Longer effects on search behaviours appear to be positive. A randomised controlled trial is valuable in identifying cause-and-effect relations and to quantify the magnitude of the effects for management decision-making.", "We investigated whether patient-centered communication skills can be taught to residents in Internal Medicine by using a time-limited behaviorally oriented intervention.\n Residents working at the Department of Internal Medicine were randomly assigned to an intervention group (IG; N = 19) or a control group (CG; N = 23). In addition to 6 hours of standard medical education per week, the IG received specific communication training of 22.5 hours duration within a 6-month period. Initially and 10 months later, participants performed interviews with simulated patients. Interviews were rated by blinded raters who used the Maastricht History and Advice Checklist-Revised.\n Compared with the CG, the IG improved substantially in many specific communication skills. Both groups improved in the \"amount of medical information identified\" and in the ability to \"communicate about feasibility of treatment.\"\n Patient-centered communication skills such as those presented in this intervention study can be taught. The ability to gain medical information and the readiness to communicate about aspects of medical treatment seem to improve with more professional experience; however, they also profit from the intervention.", "It is important for patients to provide relevant information to the doctor in consultation and to make their own information requirements known. This requires patients to actively participate in the process, something they appear to be reluctant to do. Earlier patient intervention studies have successfully manipulated patient involvement and question asking, although, the latter has tended to be accompanied by increased tension and negative impact. The present study uses a patient education leaflet which uses a wide definition of patient activation. It emphasizes the role of the 'good' patient as a provider of information extending beyond the recitation of symptoms to include insights to interpretation and meaning. Results showed that patients responded positively to the leaflet and a comparison of doctor ratings of communication quality showed the experimental group performed better than the controls. The findings are considered in terms of improved information exchange and the impact of making the 'rules' of consultation explicit is also discussed.", "Client-centered care is a major aim of health care. In mental health, new client-centered treatment approaches that emphasize recovery, rehabilitation, and empowerment can improve outcomes for people with severe and persistent mental illness. However, these approaches are not widely used, in part because many clinicians lack the necessary competencies. The objective of this study was to evaluate the effectiveness of an innovative, consumer-led intervention, Staff Supporting Skills for Self-Help, which was designed to improve provider quality, empower mental health consumers, and promote mutual support.\n The study was conducted at five large community mental health provider organizations in two western states. One organization in each state received the intervention. The intervention included education, clinician-client dialogues, ongoing technical assistance, and support of self-help. It focused on client-centered care, rehabilitation, and recovery. A one-year controlled trial evaluated the effect of the intervention on clinicians' competencies, care processes, and the formation of mutual support groups. Outcomes were assessed by using competency assessment survey instruments and semistructured interviews with clinicians and managers.\n A total of 269 clinicians participated in the study: 151 in the intervention group and 118 in the control group. Compared with clinicians at the control organizations, clinicians at intervention organizations showed significantly greater improvement in education about care, rehabilitation methods, natural supports, holistic approaches, teamwork, overall competency, and recovery orientation.\n A feasible, consumer-led intervention improves provider competencies in domains that are necessary for the provision of high-quality care.", "Paternalistic models of health care, social distance between patients and providers, and cultural norms discourage patients from playing an active role in health consultations. This study tested whether individual coaching can give family planning patients the confidence and communication skills to talk more openly and more vigorously with providers. Educators met with 384 Indonesian women in clinic waiting rooms and coached them on asking questions, expressing concerns, and seeking clarification. An analysis of audiotaped consultations found that patients who received coaching articulated significantly more questions and concerns than others. Coaching narrowed differentials in active communication by patient type, age, and assertiveness, but it widened differentials by patient education and socioeconomic class. The discontinuation rate at 8 months was lower in the intervention than the control condition, but the difference was only marginally significant.", "Management of diabetes is frequently suboptimal in primary care settings, where providers often fail to intensify therapy when glucose levels are high, a problem known as clinical inertia. We asked whether interventions targeting clinical inertia can improve outcomes.\n A controlled trial over a 3-year period was conducted in a municipal hospital primary care clinic in a large academic medical center. We studied all patients (4,138) with type 2 diabetes who were seen in continuity clinics by 345 internal medicine residents and were randomized to be control subjects or to receive one of three interventions. Instead of consultative advice, the interventions were hard copy computerized reminders that provided patient-specific recommendations for management at the time of each patient's visit, individual face-to-face feedback on performance for 5 min every 2 weeks, or both.\n Over an average patient follow-up of 15 months within the intervention site, improvements in and final HbA1c (A1C) with feedback + reminders (deltaA1C 0.6%, final A1C 7.46%) were significantly better than control (deltaA1C 0.2%, final A1C 7.84%, P < 0.02); changes were smaller with feedback only and reminders only (P = NS vs. control). Trends were similar but not significant with systolic blood pressure (sBP) and LDL cholesterol. Multivariable analysis showed that the feedback intervention independently facilitated attainment of American Diabetes Association goals for both A1C and sBP. Over a 2-year period, overall glycemic control improved in the intervention site but did not change in other primary care sites (final A1C 7.5 vs. 8.2%, P < 0.001).\n Feedback on performance aimed at overcoming clinical inertia and given to internal medicine resident primary care providers improves glycemic control. Partnering generalists with diabetes specialists may be important to enhance diabetes management in other primary care settings.", "A consulting method known as 'shared decision making' (SDM) has been described and operationalized in terms of several 'competences'. One of these competences concerns the discussion of the risks and benefits of treatment or care options-'risk communication'. Few data exist on clinicians' ability to acquire skills and implement the competences of SDM or risk communication in consultations with patients.\n The aims of this study were to evaluate the effects of skill development workshops for SDM and the use of risk communication aids on the process of consultations.\n A cluster randomized trial with crossover was carried out with the participation of 20 recently qualified GPs in urban and rural general practices in Gwent, South Wales. A total of 747 patients with known atrial fibrillation, prostatism, menorrhagia or menopausal symptoms were invited to a consultation to review their condition or treatments. Half the consultations were randomly selected for audio-taping, of which 352 patients attended and were audio-taped successfully. After baseline, participating doctors were randomized to receive training in (i) SDM skills or (ii) the use of simple risk communication aids, using simulated patients. The alternative training was then provided for the final study phase. Patients were allocated randomly to a consultation during baseline or intervention 1 (SDM or risk communication aids) or intervention 2 phases. A randomly selected half of the consultations were audio-taped from each phase. Raters (independent, trained and blinded to study phase) assessed the audio-tapes using a validated scale to assess levels of patient involvement (OPTION: observing patient involvement), and to analyse the nature of risk information discussed. Clinicians completed questionnaires after each consultation, assessing perceived clinician-patient agreement and level of patient involvement in decisions. Multilevel modelling was carried out with the OPTION score as the dependent variable, and rater, consultation and clinician levels of data, standardized by rater within clinician.\n Following each of the interventions, the clinicians significantly increased their involvement of patients in decision making (OPTION score increased by 10.6 following risk communication training [95% confidence interval (CI) 7.9 -13.3; P < 0.001] and by 12.9 after SDM skill development (95% CI 10 -15.8, P < 0.001), a moderate effect size. The level of involvement achieved by the risk communication aids was significantly increased by the subsequent introduction of the skill development workshops (7.7 increase in OPTION score, 95% CI 3.4-12; P < 0.001). The alternative sequence (skills followed by risk communication aids) did not achieve this effect. The use of most risk information formats increased after the provision of specific risk communication aids (P < 0.001). Clinicians using the risk communication tools perceived significantly higher patient and clinician agreement on treatment (P < 0.001), patient satisfaction with information (P < 0.01), clinician satisfaction with decision (P < 0.01) and general overall satisfaction with the consultation (P < 0.001) than those who were exposed to SDM skill development workshops.\n These clinicians were able to acquire the skills to implement SDM competences and to use risk communication aids. Each intervention provided independent effects. Further progress towards greater patient involvement in health care decision making is possible, and skill development in this area should be incorporated into postgraduate professional development programmes.", "To determine the impact of a hospital-coordinated discharge care plan, involving a multidisciplinary team of primary health care providers, on hospital length of stay, quality of life, and both patient and general practitioner inclusion in, and satisfaction with, discharge procedures.\n This investigation comprised a prospective, randomized, controlled, clinical trial.\n This multicentre and cross-jurisdictional study focused on areas of tertiary and primary health care as well as community allied health in Western Australia.\n Patients (n = 189) with chronic cardiorespiratory diagnoses were recruited from respiratory, cardiovascular, and general medical wards at two tertiary hospitals.\n Subjects were randomly assigned to one of two groups. Intervention group patients received a discharge care plan in accordance with that outlined in the Australian Enhanced Primary Care Package, completed before discharge and sent to the patient's general practitioner and other community service providers for review. Control patients were discharged under existing hospital processes. Outcome measures. Patients and general practitioners were surveyed pre-discharge and 7 days post-discharge for quality of life and opinion of discharge procedures. Hospital length of stay was also determined.\n Significant improvements in discharge planning involvement, health service access, confidence with discharge procedures, and opinion of discharge based on previous experience were seen for patients who received the discharge care plan. Further, improved perceptions of mental quality of life were observed within the first week post-discharge for intervention patients. Length of stay showed no difference between groups. Extent and speed of hospital-general practitioner communication were significantly improved via the intervention.\n Our results indicate that a multidisciplinary discharge care plan, initiated before separation, improves quality of life, involvement, and satisfaction with discharge care, and hospital-general practitioner integration. As such, it possesses benefits over current Western Australian hospital discharge procedures for the care of chronically ill populations.", "The purpose of this randomized controlled trial was to test the efficacy and effectiveness of process consultation consisting of a series of nurse manager-consultant problem-solving meetings for leadership development that would lead to their staff's improved morale, quality of care, and reduced absenteeism.\n Thirteen consenting clinical inpatient units were stratified for four variables known to affect outcome and were then randomly assigned to treatment and control conditions. The nurse managers from the seven experimental units were paired with outside nurse consultants from the McMaster University School of Nursing (Hamilton, Ontario, Canada) in a cooperative form of retraining in problem-solving through process consultation. Morale was determined through measures of perceptions of the work environment, an attitude scale concerning work (alienation), a personality measure (hardiness), and one of each scale for work satisfaction and for sources of satisfaction and dissatisfaction. Demographic data and information regarding family life responsibilities were collected as well. Assessment of quality of care was determined by the frequency and type of incident reports and by patients' perception of their satisfaction. A ratio of absence hours to total paid hours of work was used to compare experimental and control units' absenteeism rates.\n Experimental subjects reported a statistically significant improvement in the characteristics of their work setting and in the quality of working relationships. The consultation process facilitated a perceived change in the organizational context of the experimental hospital units with less centralization of authority and more clarity about expectation. These organizational changes were accompanied by improved working relationships and less alienation from work. There was no statistically significant difference in absenteeism. However, a subanalysis of the units by \"dose\" of the intervention identified those who benefited from the effects of the consultation. Subjects whose nurse managers participated more actively in the consultation process accounted for the changes in working relationships and perceived organizational changes. The \"low-dose\" experimental subjects were more like the control subjects, with the exception of absenteeism, for which they had higher rates.\n The findings of this study suggest that process consultation can alter the staff's perceptions of the characteristics of the work setting, can reverse negative attitudes (alienation), and can create a more positive and supportive working environment (improved working relationship). However, the results suggest the need to target this type of intervention to managers who have the personal resources to engage in self-evaluation and personal development and thus to participate in the consultative process.", "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.", "Older persons frequently experience a decline in function following an acute medical illness and hospitalization.\n To test the hypothesis that a multicomponent intervention, called Acute Care for Elders (ACE), will improve functional outcomes and the process of care in hospitalized older patients.\n Randomized controlled trial.\n Community teaching hospital.\n A total of 1,531 community-dwelling patients, aged 70 or older, admitted for an acute medical illness between November 1994 and May 1997.\n ACE includes a specially designed environment (with, for example, carpeting and uncluttered hallways); patient-centered care, including nursing care plans for prevention of disability and rehabilitation; planning for patient discharge to home; and review of medical care to prevent iatrogenic illness.\n The main outcome was change in the number of independent activities of daily living (ADL) from 2 weeks before admission (baseline) to discharge. Secondary outcomes included resource use, implementation of orders to promote function, and patient and provider satisfaction.\n Self-reported measures of function did not differ at discharge between the intervention and usual care groups by intention-to-treat analysis. The composite outcome of ADL decline from baseline or nursing home placement was less frequent in the intervention group at discharge (34% vs 40%; P = .027) and during the year following hospitalization (P = .022). There were no significant group differences in hospital length of stay and costs, home healthcare visits, or readmissions. Nursing care plans to promote independent function were more often implemented in the intervention group (79% vs 50%; P = .001), physical therapy consults were obtained more frequently (42% vs 36%; P = .027), and restraints were applied to fewer patients (2% vs 6%; P = .001). Satisfaction with care was higher for the intervention group than the usual care group among patients, caregivers, physicians, and nurses (P < .05).\n ACE in a community hospital improved the process of care and patient and provider satisfaction without increasing hospital length of stay or costs. A lower frequency of the composite outcome ADL decline or nursing home placement may indicate potentially beneficial effects on patient outcomes.", "This study examined the efficacy of a brief written intervention for primary care patients, designed to increase their level of participation in the consultation. Patients given the intervention leaflet (N = 59) were compared with those given a control leaflet (N = 61) on various consultation process and outcome measures. Psychological and sociodemographic data were also obtained to determine whether these influenced the effects of the intervention. The results showed that the intervention group had significantly longer consultations and asked more questions than the controls. Younger patients and those from social classes 1 and 2 were more likely to benefit from the intervention, but locus of control and self-efficacy scores were not particularly helpful in predicting outcomes. No differences in patient satisfaction were found nor were any negative effects on the doctor observed. A number of explanations are explored and some directions for future research are discussed.", "To present the results of a pilot study testing an intervention designed to improve the quality of medical consultations between breast cancer patients and physicians and, in particular, to report the effects of the intervention on the quality of treatment decisions, the quality of communication, and the satisfaction of patients and physicians.\n We enrolled 24 predominantly white, well-educated, early-stage breast cancer patients who were facing local or systemic treatment decisions in a sequential, controlled trial. All patients received a visit preparation session before the consultation in which a trained researcher helped patients organize their questions and concerns. In the control, a researcher observed the consultation. In the intervention, a researcher helped create an agenda, facilitated the discussion, and created a record of the consultation in real time. Valid and reliable surveys measured the quality of treatment decisions and satisfaction with the consultation.\n Patients in the intervention achieved significantly higher final decision quality scores compared with control patients (median score, 14 v 10, respectively; P =.008) and a significantly higher level of intersubjective agreement with their physicians about decision quality (Cohen's kappa, 0.49 v 0.285, respectively; P <.0001). Consultation recording methods did not affect the length of time required for the consultation.\n Consultation recording methods provide a promising innovation for medical consultations. Further studies are warranted to broaden the findings, assess impacts on the quality of decisions, cost, and health, and develop practical ways to integrate consultation recording methods into clinics.", "Active participation in the medical consultation has been demonstrated to benefit aspects of patients' subsequent psychological well-being. We investigated two interventions promoting patient question-asking behaviour. The first was a question prompt sheet provided before the consultation, which was endorsed and worked through by the clinician. The second was a face to face coaching session exploring the benefits of, and barriers to, question-asking, followed by coaching in question-asking behaviour employing rehearsal techniques. Sixty patients with heterogeneous cancers, seeing two medical oncologists for the first time, were randomly assigned to one of three groups: two intervention groups and one control group. Sociodemographic variables and anxiety were assessed prior to the intervention which preceded the consultation. The consultations were audiotaped and subsequently analysed for question-asking behaviour. Anxiety was assessed again immediately following the consultation. Questionnaires to assess patient satisfaction, anxiety and psychological adjustment were sent by mail 2 weeks following the consultation. Presentation and discussion of the prompt sheet significantly increased the total number of questions asked and the number of questions asked regarding tests and treatment. Coaching did not add significantly to the effects of the prompt sheet. Psychological outcomes were not different among the groups. We conclude that a question prompt sheet addressed by the doctor is a simple, inexpensive and effective means of promoting patient question asking in the cancer consultation.", "An intervention was developed to increase patient involvement in care. Using a treatment algorithm as a guide, patients were helped to read their medical record and coached to ask questions and negotiate medical decisions with their physicians during a 20-minute session before their regularly scheduled visit. In a randomized controlled trial we compared this intervention with a standard educational session of equal length in a clinic for patients with ulcer disease. Six to eight weeks after the trial, patients in the experimental group reported fewer limitations in physical and role-related activities (p less than 0.05), preferred a more active role in medical decision-making, and were as satisfied with their care as the control group. Analysis of audiotapes of physician-patient interactions showed that patients in the experimental group were twice as effective as control patients in obtaining information from physicians (p less than 0.05). Results of the intervention included increased involvement in the interaction with the physician, fewer limitations imposed by the disease on patients' functional ability, and increased preference for active involvement in medical decision-making.", "No evidence addresses the effectiveness of patient-centered cultural competence training in non-Western settings.\n To examine whether a patient-centered cultural competency curriculum improves medical students' skills in eliciting the patients' perspective and exploring illness-related social factors.\n Fifty-seven medical students in Taiwan were randomly assigned to either the control (n = 27) or one of two intervention groups: basic (n = 15) and extensive (n = 15). Both intervention groups received two 2-hour patient-centered cultural competency workshops. In addition, the extensive intervention group received a 2-hour practice session. The control group received no training.\n At the end of the clerkship, all students were evaluated with an objective structured clinical examination (OSCE). Students in the extensive intervention group scored significantly higher than the basic intervention and control groups in eliciting the patient's perspective (F = 18.38, p < 0.001, eta(2) = 0.40). Scores of both intervention groups were significantly higher than the control group in the exploring social factors (F = 6.66, p = 0.003, eta(2) = 0.20).\n Patient-centered cultural competency training can produce improvement in medical students' cross-cultural communication skills in non-Western settings, especially when adequate practice is provided.", "When patients are active participants in discussions, comprehension and compliance are likely to improve. This study examines the use of two interventions to aid patients in initiating such discussions in the area of health maintenance.\n The study was a randomized controlled trial of adult patients. The first intervention used two cards that listed seven core health maintenance concerns. The second intervention used a brief session with a nurse to help patients identify their health risks and develop a plan for seeking any desired information about these risks. An exit questionnaire and a telephone interview 4 to 6 weeks later assessed the extent to which (1) information seeking by patients was stimulated; (2) patients recalled the information obtained; (3) patients used the information to effect lifestyle changes; and (4) patients felt they participated in the decision to discuss health maintenance.\n Both interventions stimulated patients to request health maintenance information (both P < .05); the second intervention significantly increased patient recall (P = .018). Neither intervention, however, had a significant impact on lifestyle change or sense of participation in the decision to initiate discussion. Analysis of the second intervention did show that both increasing patients' recall of information (P = .008) and sense of involvement in the decision to discuss health maintenance (P = .003) significantly increases the likelihood of lifestyle change.\n Two interventions have been developed that are relatively simple and inexpensive methods to stimulate patients to seek health maintenance, and quite probably other health-related information. The blunted impact of these two interventions, however, raises the question of whether such simple and relatively inexpensive interventions are strong enough to stimulate patients to use this information to initiate change when one seeks to address a wide range of risks.", "Shared decision making (SDM) involves patients and doctors contributing as partners to treatment decisions. It is not known whether or to what extent SDM contributes to the welfare arising from a consultation, and how important this contribution is relative to other attributes of a consultation.\n To identify patient preferences for SDM relative to other utility bearing attributes of a consultation.\n In parallel with a randomised trial in training GPs in SDM competencies and risk communication skills, a discrete choice experiment exercise was conducted to assess patients' utilities.\n Twenty general practices in South Wales, UK.\n Five hundred and eighty-four responders from 747 patients attending the randomised trial (response rate = 78%). All patients had one of four conditions (atrial fibrillation, menorrhagia, menopausal symptoms or prostatism) and attended a consultation with a doctor in their own practice. Patients were randomised to attend a consultation either with a doctor who had received no training in the study or risk communication training alone or SDM training alone, or both combined.\n Five key utility bearing attributes of a consultation were identified. All significantly influenced patient's choice of preferred consultation style (P<0.001). Larger increases in utility were associated with changes on \"doctor listens\" attribute, followed by easily understood information, a shared treatment decision, more information and longer consultation. Utilities were influenced by whether the doctor had received risk communication training alone or SDM training alone, or both combined, prior to the consultations. The randomised trial itself had identified that the communication processes of these consultations changed significantly, with greater patient involvement in decision making, after the training interventions.\n Shared treatment decisions were valued less than some other attributes of a consultation. However, patient utilities for such involvement appeared responsive to changes in experiences of consultations. This suggests that SDM may gain greater value among patients once they have experienced it.", "The aim of this study was to determine if nurses, using patient-centered care (PCC), affect patient satisfaction, perceptions of nursing care, and quality outcomes.\n The Institute of Medicine proposed PCC as 1 of 6 national quality aims, whereas the Centers for Medicare and Medicaid Services highlighted integration of PCC as 1 of 12 actions for quality improvement.\n A total of 116 patients were randomized into an intervention (PCC) or control group. Patients who were to receive PCC were called before admission and cared for by nurses who trained to administer/practice PCC. Control patients received usual care. Both groups completed questionnaires and received postdischarge calls. Length of stay, falls, infections, and adverse events were measured to assess quality of care.\n No significant differences were found between groups for length of stay, infection, falls, postoperative complications, quality of care, satisfaction level, or perceptions of nursing care.\n Patient-centered care did not affect patient's level of satisfaction or quality of care. However, findings yielded clinically relevant results regarding patient/staff responses.", "The need for training to equip primary care staff with the knowledge and skills to provide dietary advice to the public has been acknowledged. Little is known about the effectiveness of such training at improving the dietary counselling skills of multidisciplinary practice teams.\n To evaluate the effectiveness of a nutrition training programme, delivered to primary care teams by a dietitian.\n A paired-cluster randomised trial.\n Twelve general practices in Sunderland, in the United Kingdom.\n A nutrition training programme, aimed at improving the quality of dietary consultations, was developed and delivered to six primary care teams by a dietitian. Main outcome measures were patients' recall of seven key consulting behaviours. Data were collected from patients in intervention and control practices, pre- and post-intervention. Change in knowledge and attitude of practitioners was also measured.\n All 12 practices completed the trial. Data were collected from 251 patients pre-intervention and 228 patients post-intervention. Of the seven consulting behaviours targeted in the training, only the proportion of consultations where written information (diet sheets) was provided to patients was significantly higher (13% higher, 95% confidence interval [CI = 4 to 21, P = 0.004) in the intervention practices post-training. Some evidence of improved practitioner knowledge and attitude was detected.\n This evaluation of a nutrition training intervention detected only a limited impact on the behaviour, knowledge, and attitudes of primary care practitioners in dietary consultations.", "We prompted parents to increase their interactions with health-care providers during their children's health-supervision visits. Before scheduled appointments we asked parents of 32 infants and young children if they had specific child health questions or concerns. Sixteen parents randomly assigned to the prompted group were then prompted to initiate discussions of their concerns. Sixteen control parents discussed unrelated topics before their appoitments. Prompted parents initiated significantly more interactions with health-care providers and more health and behavioral topics were discussed during their appointments. Both parent groups reported satisfaction with health-care services. Further research is needed to determine the clinical significance of outcomes associated with enhanced parent-provider interaction during children's health-supervision visits. These visits are ideal settings for behavioral research on improving health care for children and their families.", "Doctor-patient communication is an essential component of general practice. Improvement of GPs' communication patterns is an important target of training programmes. Available studies have so far failed to provide conclusive evidence of the effectiveness of educational interventions to improve doctor-patient communication.\n To examine the effectiveness of a learner-centred approach that focuses on actual needs, to improve GPs' communication with patients.\n Randomised controlled trial.\n One hundred volunteer GPs in the Netherlands.\n The intervention identified individual GPs' deficiencies in communication skills by observing authentic consultations in their own surgery. This performance assessment was followed by structured activities in small group meetings, aimed at remedying the identified shortcomings. Outcomes were measured using videotaped consultations in the GPs' own surgery before and after the intervention. Communication skills were rated using the MAAS-Global, a validated checklist.\n The scores in the intervention group demonstrated a significant improvement compared with those of the control group (95% confidence interval = 0.04 to 0.75). The effect size was moderate to large (d-value = 0.66). The level of participation significantly contributed to the effectiveness. Largest improvement was found on patient-centred communication skills.\n The approach of structured individual improvement activities based on performance assessment is more effective in improving communication skills than current educational activities.", "We conducted a 4-year randomized study in a community health center that serves primarily low income Blacks in Durham, North Carolina. Patients (1318 at baseline) were assigned randomly to one of three study groups: provider prompting intervention alone, provider prompting and tailored print materials or the previous group and tailored telephone counseling. The purpose of the study was to determine whether increasingly intensive, tailored print and telephone interventions also were increasingly effective in promoting adherence to mammograms, Pap tests and overall cancer screening compliance. Thus, the combination of tailored print interventions (print and telephone) should have been more effective than the provider prompting intervention alone, or the print intervention and prompting combination. This is one of the few studies to examine a measure of overall cancer screening compliance and to assess the benefit of combinations of tailored interventions in promoting adherence to cancer screening. Patients gave extremely high ratings to the interventions. At the bivariate level, we found a significant effect of the most intensive group (provider prompting intervention, tailored print communications and tailored telephone counseling) on Pap test compliance (P = 0.05) and borderline significance at the multivariate level (P = 0.06) as well on overall screening compliance (P = 0.06). There was not a significant effect on mammography, probably because a majority of the patients were receiving regular mammograms. We also found some important subgroup differences. For example, a larger proportion of women reported Pap tests in the tailored print and counseling group when they believed the materials were 'meant for me.' These results show that a combination of tailored interventions may have potential for reaching the women who have too often been labeled the 'hard to reach.'", "This investigation examined factors affecting patient involvement in consultations to decide local treatment for early breast cancer and the effectiveness of two methods of preconsultation education aimed at increasing patient participation in these discussions.\n Sixty patients with Stage I or II breast cancer (1) were pretested on their knowledge about breast cancer treatment and optimism for the future, (2) were randomly assigned to one of two methods for preconsultation education: interactive multimedia program or brochure, (3) completed knowledge and optimism measures, (4) consulted with a medical oncologist, radiation oncologist, and general surgeon, and (5) completed self-report measures assessing their involvement in the consultations and control over decision-making. The consultations were audiorecorded and analyzed to identify behavioral indicators of patient involvement (question-asking, opinion-giving, and expressing concern) and physician utterances encouraging patient participation.\n College-educated patients younger than 65 years of age were more active participants in these consultations than were older, less educated patients. In addition, patients showed more involvement when they interacted with physicians who encouraged and facilitated patient participation. The method of education did not affect patient involvement although patients tended to learn more about breast cancer treatment after using the multimedia program than after reading the brochure.\n Although patients vary in their expressiveness, physicians may be able to increase patient participation in deciding treatment by using patient-centered behavior. Also, preconsultation education appears to be an effective clinical strategy for helping patients gain an accurate understanding of their treatment options before meeting with physicians.", "Although clinical-practice guidelines (CPGs) are implemented on the assumption that they will improve the quality, efficiency, and consistency of health care, they generally have limited effect in changing physicians' behavior. The purpose of this study was to design and implement an effective program for formulating, promulgating, and implementing CPGs to foster the development of an evidence-based culture in an Israeli HMO.\n The authors implemented a four-stage program of stepwise collaborative efforts with academic institutions composed of developing quantitative tools to evaluate prescribing patterns, updating CPGs, collecting MDs' input via focus groups and quantitative surveys, and conducting a randomized controlled trial of a two-stage, multipronged intervention. The test case for this study was the development, dissemination, and implementation of CPG for the treatment of acute uncomplicated cystitis in adult women. Interventions in the form of a lecture at a conference and a letter with personalized feedback were implemented, both individually and combined, to improve physicians' rates of prescribing the first-line drug, nitrofurantoin, and, in the absence of nitrofurantoin, adhering to the recommended duration of three days of treatment with ofloxacin.\n The tools and data-generating capabilities designed and constructed in Stage I of the project were integral components of all subsequent stages of the program. Personalized feedback alone was sufficient to improve the rate of adherence to the guidelines by 19.4% (95% CI = 16.7, 22.1).\n This study provides a template for introducing the component of experimentation essential for cultivating an evidence-based culture. This process, composed of collaborative efforts between academic institutions and a managed care organization, may be beneficial to other health care systems.", "Patients with persistent medically unexplained symptoms often exhibit general dysfunction and psychiatric comorbidity and frequently resist psychiatric referral. The aim of this study was to evaluate the efficacy of a collaborative care model including training for general practitioners (GPs) and a psychiatric consultation model for patients with persistent medically unexplained symptoms in general practice.\n Randomised controlled trial. Cluster randomisation at GP practices and multilevel analysis were performed. A total of 81 patients from 36 general practices completed the study. A collaborative care model of training and psychiatric consultation in general practice in the presence of the GP was compared with training plus care as usual by the GP. Outcome assessment on the patients' well-being, functioning and utilisation of health care services was performed 6 weeks and 6 months later.\n All the patients had somatoform disorders (Whitely Index 7.46), and 86% had comorbid psychiatric disorders. In the intervention group, the severity of the main medically unexplained symptoms decreased by 58%. The patients' social functioning improved. The utilization of health care was lower than in the care as usual group.\n A collaborative care model combining training with psychiatric consultation in the general practice setting is an effective intervention in the treatment of persistent medically unexplained symptoms. Anxiety and depressive disorders are highly comorbid in this group. The findings warrant a larger study.", "Current understanding of implementation methods is limited, and research has focused on changing doctors' behaviors.\n Our aim was to evaluate the impact of audit and feedback and educational outreach in improving nursing practice and patient outcomes.\n Using a factorial design, cluster randomized controlled trial, we evaluated 194 community nurses in 157 family practices and 1078 patients with diagnosis of urinary incontinence (UI) for nurses compliance with evidence-linked review criteria for the assessment and management of UI and impact on psychologic and social well-being and symptoms. In the outreach arms, nurses' self-reported barriers informed development of tailored strategies.\n In comparison with educational materials alone, the implementation methods tested did not improve care at 6 months follow-up. Moderate rates of improvement (10-17% of patients) in performance for the assessment of UI and greater rates of improvement (20-30% of patients) for the management of care were found but effects were similar across arms. Improvement in patient outcomes was more consistently positive for educational outreach than for audit and feedback but differences were not significant. Adjustment for caseload size, severity or duration of UI and patients' age did not alter results.\n Printed educational materials alone may be as effective as audit and feedback and educational outreach in improving nurses' performance and outcomes of care for people with UI. Greater understanding of the underlying processes in improving performance within multidisciplinary teams through further, theory-driven studies with \"no intervention\" control groups and longer follow-up are needed.", "Much of the research on decision-making in health care has focused on consultation outcomes. Less is known about the process by which clinicians and patients come to a treatment decision. This study aimed to quantitatively describe the behaviour shown by doctors and patients during primary care consultations when three types of decision aids were used to promote treatment decision-making in a randomised controlled trial.\n A video-based study set in an efficacy trial which compared the use of paper-based guidelines (control) with two forms of computer-based decision aids (implicit and explicit versions of DARTS II). Treatment decision concerned warfarin anti-coagulation to reduce the risk of stroke in older patients with atrial fibrillation. Twenty nine consultations were video-recorded. A ten-minute 'slice' of the consultation was sampled for detailed content analysis using existing interaction analysis protocols for verbal behaviour and ethological techniques for non-verbal behaviour.\n Median consultation times (quartiles) differed significantly depending on the technology used. Paper-based guidelines took 21 (19-26) minutes to work through compared to 31 (16-41) minutes for the implicit tool; and 44 (39-55) minutes for the explicit tool. In the ten minutes immediately preceding the decision point, GPs dominated the conversation, accounting for 64% (58-66%) of all utterances and this trend was similar across all three arms of the trial. Information-giving was the most frequent activity for both GPs and patients, although GPs did this at twice the rate compared to patients and at higher rates in consultations involving computerised decision aids. GPs' language was highly technically focused and just 7% of their conversation was socio-emotional in content; this was half the socio-emotional content shown by patients (15%). However, frequent head nodding and a close mirroring in the direction of eye-gaze suggested that both parties were active participants in the conversation\n Irrespective of the arm of the trial, both patients' and GPs' behaviour showed that they were reciprocally engaged in these consultations. However, even in consultations aimed at promoting shared decision-making, GPs' were verbally dominant, and they worked primarily as information providers for patients. In addition, computer-based decision aids significantly prolonged the consultations, particularly the later phases. These data suggest that decision aids may not lead to more 'sharing' in treatment decision-making and that, in their current form, they may take too long to negotiate for use in routine primary care.", "This 24-month exploratory study evaluated whether a 6-month programme supported by a trained external facilitator was feasible, acceptable and led to the adoption of a multidisciplinary approach to audit by secondary care staff. Undertaken in five acute hospital sites in the East Midlands UK, 22 multidisciplinary teams were randomised to either an intervention or control arm. Employing mixed methods, a range of outcomes, including collaborative behaviour, was measured. The intervention was feasible and acceptable to staff. Involvement in the facilitated programme had a positive impact on self-reported knowledge (P=0.000 post-intervention and at 4-months follow-up), skills (P=0.000 post-intervention and P=0.02 at 4-months follow-up) and attitudes (P<0.01 post-intervention), appeared to have some influence on improving self-reported (P<0.05 post-intervention) and observed collaborative behaviour (P=0.01) and led to better quality audit resulting in measurable improvements to care. Improved collaborative behaviour may have resulted from an increase in assertive behaviour by nurses. Research to test approaches to support teams to work effectively together is currently hampered by a lack of suitable research instruments and needs addressing before main (phase 111) trials are undertaken.", "There is a well-documented gap between diabetes care guidelines and the services received by patients in almost all health care settings. This project reports initial results from a computer-assisted, patient-centered intervention to improve the level of recommended services received by patients from a wide variety of primary care providers.\n Eight hundred eighty-six patients with type 2 diabetes under the care of 52 primary care physicians participated in the Diabetes Priority Program. Physicians were stratified and randomized to intervention or control conditions and evaluated on 2 primary outcomes: number of recommended laboratory screenings and recommended patient-centered care activities completed. Secondary outcomes were evaluated using the Problem Areas in Diabetes scale and the Patient Health Questionnaire (PHQ)-9 depression scale, and the RE-AIM framework was used to evaluate potential for dissemination.\n The program was well-implemented and significantly improved both number of recommended laboratory assays (3.4 vs 3.1; P <.001) and patient-centered aspects of diabetes care patients received (3.6 vs 3.2; P <.001) compared to those in randomized control practices. Activities that were increased most were foot exams (follow-up rates of 80% vs 52%; P <.003) and nutrition counseling (76% vs 52%; P <.001).\n Patients are very willing to participate in a brief computer-assisted intervention that is effective in enhancing quality of diabetes care. Staff in primary care offices can consistently deliver an intervention of this nature, but most physicians were unwilling to participate in this translation research study.", "The purpose of this study was to investigate the effectiveness, dynamics, and consequences of a health education intervention designed to increase patient question asking during the patient's medical visit. Data were collected at a Baltimore family and community health center which provides outpatient services to a low income, predominantly black and female population. The majority of the study participants were, in addition, elderly and chronically ill. A total of 294 patients and 3 providers took part in the study. The study design included random assignment of patients to experimental and placebo groups with two non-equivalent (non-randomized) control groups. Findings included: (1) The experimental group patients asked more direct questions and fewer indirect questions than did placebo group patients. (2) The experimental group patient-provider interaction was characterized by negative affect, anxiety, and anger, while the placebo group patient-provider interaction was characterized as mutually sympathetic. (3) The experimental group patients were less satisfied with care received in the clinic on the day of their visit than were placebo patients. (4) The experimental group patients demonstrated higher appointment-keeping ratios (an average number of appointments kept divided by an average number of appointments made) during a four-month prospective monitoring period.", "Active involvement of patients in medical encounters has been associated with several desirable outcomes, including greater satisfaction, increased adherence to treatment, and positive treatment outcomes. Older patients, particularly the very old and less well educated, are more likely to place physicians in a dominant role and themselves in a submissive role. Intervention trials to increase patient involvement have shown positive results. Activation interventions with older patients to increase a sense of control and self-efficacy are promising. Most of the attention to improving doctor-patient interaction has been directed toward physicians. The results of these few intervention trials support increased attention to patient behaviors.", "Improving precision and economy in the prescribing of drugs is a goal whose importance has increased with the proliferation of new and potent agents and with growing economic pressures to contain health-care costs. We implemented an office-based physician education program to reduce the excessive use of three drug groups: cerebral and peripheral vasodilators, an oral cephalosporin, and propoxyphene. A four-state sample of 435 prescribers of these drugs was identified through Medicaid records and randomly assigned to one of three groups. Physicians who were offered personal educational visits by clinical pharmacists along with a series of mailed \"unadvertisements\" reduced their prescribing of the target drugs by 14 per cent as compared with controls (P = 0.0001). A comparable reduction in the number of dollars reimbursed for these drugs was also seen between the two groups, resulting in substantial cost savings. No such change was seen in physicians who received mailed print materials only. The effect persisted for at least nine months after the start of the intervention, and no significant increase in the use of expensive substitute drugs was found. Academically based \"detailing\" may represent a useful and cost-effective way to improve the quality of drug-therapy decisions and reduce unnecessary expenditures.", "High experienced continuity of care in patients with cancer is associated with lower needs for care, better quality of life and better psychological outcomes. We developed and evaluated an intervention to improve experienced continuity. The intervention, consisted of (1) a 17-item patient-completed continuity assessment; (2) feedback to clinical nurse specialists and action to address the needs identified. Multidisciplinary team meetings and oncology outpatient clinics were observed, and patients and staff were interviewed. After qualitative work and reliability testing, the intervention was evaluated in a feasibility trial. Sixty-one patients provided data for analysis. No statistically significant differences were found in patients' experienced continuity between the trial arms, but important trends were seen in measures of needs for care in favour of those receiving the intervention. Feeding back findings from the continuity assessment to clinicians reduced patients' needs for care. Our results indicate that an intervention to target patients' experiences of continuity can reduce their subsequent needs for care. However, overcoming barriers to organisational change and addressing some patients' hesitation to report their continuity difficulties must be considered when implementing such an intervention. A phase III trial targeting patients with inadequate experienced continuity of care is recommended." ]	Interventions to promote patient-centred care within clinical consultations are effective across studies in transferring patient-centred skills to providers. However the effects on patient satisfaction, health behaviour and health status are mixed. There is some indication that complex interventions directed at providers and patients that include condition-specific educational materials have beneficial effects on health behaviour and health status, outcomes not assessed in studies reviewed previously. The latter conclusion is tentative at this time and requires more data. The heterogeneity of outcomes, and the use of single item consultation and health behaviour measures limit the strength of the conclusions.
CD005638	[ "7823387", "10391656" ]	[ "Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials.", "Impact of study quality on outcome in placebo-controlled trials of homeopathy." ]	[ "To determine if inadequate approaches to randomized controlled trial design and execution are associated with evidence of bias in estimating treatment effects.\n An observational study in which we assessed the methodological quality of 250 controlled trials from 33 meta-analyses and then analyzed, using multiple logistic regression models, the associations between those assessments and estimated treatment effects.\n Meta-analyses from the Cochrane Pregnancy and Childbirth Database.\n The associations between estimates of treatment effects and inadequate allocation concealment, exclusions after randomization, and lack of double-blinding.\n Compared with trials in which authors reported adequately concealed treatment allocation, trials in which concealment was either inadequate or unclear (did not report or incompletely reported a concealment approach) yielded larger estimates of treatment effects (P < .001). Odds ratios were exaggerated by 41% for inadequately concealed trials and by 30% for unclearly concealed trials (adjusted for other aspects of quality). Trials in which participants had been excluded after randomization did not yield larger estimates of effects, but that lack of association may be due to incomplete reporting. Trials that were not double-blind also yielded larger estimates of effects (P = .01), with odds ratios being exaggerated by 17%.\n This study provides empirical evidence that inadequate methodological approaches in controlled trials, particularly those representing poor allocation concealment, are associated with bias. Readers of trial reports should be wary of these pitfalls, and investigators must improve their design, execution, and reporting of trials.", "We investigated the influence of indicators of methodological quality on study outcome in a set of 89 placebo-controlled clinical trials of homoeopathy in three different ways: (1) The results of studies meeting single criteria (explicit statement of random allocation, allocation concealment, double-blinding, completeness of follow-up) of methodological quality were compared with those of studies not meeting the criteria in univariate and multivariate analyses; (2) The results of studies scoring above and below predefined scores in two quality assessment scales were compared; (3) Primary studies were consecutively entered into a cumulative meta-analysis according to the summary scores derived from the quality assessment scales. All analyses were performed using meta-regression methods. Studies that were explicitly randomized and were double-blind as well as studies scoring above the cut-points yielded significantly less positive results than studies not meeting the criteria. In the cumulative meta-analyses, there was a trend for increasing effect sizes when more studies with lower-quality scores were added. However, there was no linear relationship between quality scores and study outcome. We conclude that in the study set investigated, there was clear evidence that studies with better methodological quality tended to yield less positive results. Because summarizing disparate study features into a single score is problematic, meta-regression methods simultaneously investigating the influence of single study features seem the best method for investigating the impact of study quality on outcome." ]	The conclusions of this review are limited by the lack of data. More research of higher methodological quality is needed.
CD007871	[ "9972747", "19583608", "19117801", "12039820", "773416", "16096533", "11388527", "10719945" ]	[ "Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery.", "Thromboelastography-based transfusion algorithm reduces blood product use after elective CABG: a prospective randomized study.", "Protocol based on thromboelastograph (TEG) out-performs physician preference using laboratory coagulation tests to guide blood replacement during and after cardiac surgery: a pilot study.", "Mechanical methods of reducing blood transfusion in cardiac surgery: randomised controlled trial.", "Prophylaxis in haemophilia: a double-blind controlled trial.", "Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: two parallel randomized, placebo-controlled, double-blind clinical trials.", "Efficacy of a simple intraoperative transfusion algorithm for nonerythrocyte component utilization after cardiopulmonary bypass.", "Comparison of blood-conservation strategies in cardiac surgery patients at high risk for bleeding." ]	[ "Transfusion therapy after cardiac surgery is empirically guided, partly due to a lack of specific point-of-care hemostasis monitors. In a randomized, blinded, prospective trial, we studied cardiac surgical patients at moderate to high risk of transfusion. Patients were randomly assigned to either a thromboelastography (TEG)-guided transfusion algorithm (n = 53) or routine transfusion therapy (n = 52) for intervention after cardiopulmonary bypass. Coagulation tests, TEG variables, mediastinal tube drainage, and transfusions were compared at multiple time points. There were no demographic or hemostatic test result differences between groups, and all patients were given prophylactic antifibrinolytic therapy. Intraoperative transfusion rates did not differ, but there were significantly fewer postoperative and total transfusions in the TEG group. The proportion of patients receiving fresh-frozen plasma (FFP) was 4 of 53 in the TEG group compared with 16 of 52 in the control group (P < 0.002). Patients receiving platelets were 7 of 53 in the TEG group compared with 15 of 52 in the control group (P < 0.05). Patients in the TEG group also received less volume of FFP (36 +/- 142 vs 217 +/- 463 mL; P < 0.04). Mediastinal tube drainage was not statistically different 6, 12, or 24 h postoperatively. Point-of-care coagulation monitoring using TEG resulted in fewer transfusions in the postoperative period. We conclude that the reduction in transfusions may have been due to improved hemostasis in these patients who had earlier and specific identification of the hemostasis abnormality and thus received more appropriate intraoperative transfusion therapy. These data support the use of TEG in an algorithm to guide transfusion therapy in complex cardiac surgery. Implications: Transfusion of allogeneic blood products is common during complex cardiac surgical procedures. In a prospective, randomized trial, we compared a transfusion algorithm using point-of-care coagulation testing with routine laboratory testing, and found the algorithm to be effective in reducing transfusion requirements.", "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.", "Allogenic blood transfusion may affect clinical outcomes negatively. Up to 20% of blood transfusions in the United States are associated with cardiac surgery and so strategies to conserve usage are of importance. This study compares administration according to physician's choice based on laboratory coagulation tests with application of a strict protocol based on the thromboelastograph (TEG).\n Sixty-nine patients presenting for cardiac surgery were randomised to either study or control groups. In the study group a strict protocol was followed covering usage of all blood products according to TEG patterns. In the control group, the physician directed product administration with reference to activated partial thromboplastin time (APTT), international normalised ratio (INR), fibrinogen and platelet count. Bleeding, re-sternotomy, minimum haemoglobin, intubation time, and ICU stay were documented.\n TEG-based management reduced total product usage by 58.8% in the study group but this was not statistically significant. This was associated with a statistically insignificant trend towards better short-term outcomes.\n This pilot study suggests that a strict protocol for blood product replacement based on the TEG might be highly effective in reducing usage without impairing short-term outcome.", "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.", "A double-blind controlled trial of prophylactic factor VIII therapy has been carried out on nine severe haemophiliacs at the Lord Mayor Treloar College. Infusions were given once weekly and calculated to give a post-infusion plasma concentration of at least 0.25 I.U./ml of factor VIII. This regime reduced the overall bleeding frequency by 15%. The bleeding frequency in the first 3 days post-infusion was reduced by 66%. A moderate overall reduction in morbidity was also achieved. It is calculated that to reduce the incidence of bleeding in severe haemophiliacs by 15% would require a 73% increased usage of therapeutic materials. More than twice this amount of material is likely to be needed to reduce the bleeding frequency of the same group by 66%.", "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.", "Abnormal bleeding after cardiopulmonary bypass (CPB) is a common complication of cardiac surgery, with important health and economic consequences. Coagulation test-based algorithms may reduce transfusion of non-erythrocyte allogeneic blood in patients with abnormal bleeding.\n The authors performed a randomized prospective trial comparing allogeneic transfusion practices in 92 adult patients with abnormal bleeding after CPB. Patients with abnormal bleeding were randomized to one of two groups: a control group following individual anesthesiologist's transfusion practices and a protocol group using a transfusion algorithm guided by coagulation tests.\n Among 836 eligible patients having all types of elective cardiac surgery requiring CPB, 92 patients developed abnormal bleeding after CPB (incidence, 11%). The transfusion algorithm group received less allogeneic fresh frozen plasma in the operating room after CPB (median, 0 units; range, 0-7 units) than the control group (median, 3 units; range, 0-10 units) (P = 0.0002). The median number of platelet units transfused in the operating room after CPB was 4 (range, 0-12) in the algorithm group compared with 6 (range, 0-18) in the control group (P = 0.0001). Intensive care unit (ICU) mediastinal blood loss was significantly less in the algorithm group. Multivariate analysis demonstrated that transfusion algorithm use resulted in reduced ICU blood loss. The control group also had a significantly greater incidence of surgical reoperation of the mediastinum for bleeding (11.8% vs. 0%; P = 0.032).\n Use of a coagulation test-based transfusion algorithm in cardiac surgery patients with abnormal bleeding after CPB reduced non-erythrocyte allogeneic transfusions in the operating room and ICU blood loss.", "Aprotinin and tranexamic acid are routinely used to reduce bleeding in cardiac surgery. There is a large difference in agent price and perhaps in efficacy.\n In a prospective, randomized, partially blinded study, 168 cardiac surgery patients at high risk for bleeding received either a full-dose aprotinin infusion, tranexamic acid (10-mg/kg load, 1-mg x kg(-1) x h(-1) infusion), tranexamic acid with pre-cardiopulmonary bypass autologous whole-blood collection (12.5% blood volume) and reinfusion after cardiopulmonary bypass (combined therapy), or saline infusion (placebo group).\n There were complete data in 160 patients. The aprotinin (n = 40) and combined therapy (n = 32) groups (data are median [range]) had similar reductions in blood loss in the first 4 h in the intensive care unit (225 [40-761] and 163 [25-760] ml, respectively; P = 0.014), erythrocyte transfusion requirements in the first 24 h in the intensive care unit (0 [0-3] and 0 [0-3] U, respectively; P = 0.004), and durations of time from end of cardiopulmonary bypass to discharge from the operating room (92 [57-215] and 94 [37, 186] min, respectively; P = 0.01) compared with the placebo group (n = 43). Ten patients in the combined therapy group (30.3%) required transfusion of the autologous blood during cardiopulmonary bypass for anemia.\n The combination therapy of tranexamic acid and intraoperative autologous blood collection provided similar reduction in blood loss and transfusion requirements as aprotinin. Cost analyses revealed that combined therapy and tranexamic acid therapy were the least costly therapies." ]	There is an absence of evidence that TEG or ROTEM improves morbidity or mortality in patients with severe bleeding. Application of a TEG or ROTEM guided transfusion strategy seems to reduce the amount of bleeding but whether this has implications for the clinical condition of patients is still uncertain. More research is needed.
CD007310	[ "14993717", "11035353", "16458640", "11814498", "15694088" ]	[ "Sublingual misoprostol before first trimester abortion: a comparative study using two dose regimens.", "Mifepristone versus vaginally administered misoprostol for cervical priming before first-trimester termination of pregnancy: a randomized, controlled study.", "Cervical preparation using laminaria with adjunctive buccal misoprostol before second-trimester dilation and evacuation procedures: a randomized clinical trial.", "Prostaglandin E2 gel versus misoprostol for cervical ripening in patients with premature rupture of membranes after 34 weeks.", "Cervical priming with sublingual misoprostol vs. 15-methyl-prostaglandin F2alpha prior to surgical abortion." ]	[ "Various methods have been described for preoperative cervical priming prior to vacuum aspiration (VA) in first trimester pregnancy termination, to facilitate cervical dilatation and shorten the abortion procedure. Recently misoprostol a prostaglandin E1 analogue has been shown to be effective in facilitating cervical dilatation prior to VA. Misoprostol offers several advantages over the other prostagland in analogues including stability at room temperature, ease of administration and minimal side effects.\n To determine the optimal dosage and dosing interval for the use of misoprostol administered sublingually for pre-abortion cervical dilatation.\n This was a prospective randomised study conducted at Comprehensive Rural Health Project, Ballabgarh the rural health centre under Centre for Community Medicine, AIIMS, New Delhi.\n One hundred and twenty pregnant women between 6-11 weeks of gestation opting for voluntary medical termination of pregnancy were (MTP) randomly allocated to either 200 microg or the 400 microg misoprostol group. Vacuum aspiration was performed either two or three hours after administration of sublingual misoprostol. Using Hegar's dilators, degree of cervical dilatation before vacuum aspiration was measured. Other parameters assessed included the amount of additional dilatation required, intra-operative blood loss and associated side effects.\n Statistical analysis was conducted using chisquare, the student's t and the Mann-Whitney U tests to examine the difference between the two groups.\n In the 200 microg misoprostol group 33% achieved a dilatation of > or = 8 mm compared with 71% of women in the 400 microg misoprostol group. The odds ratio was 95.8 (95% CI 10.2-842.9) for 400 microg misoprostol for successful preoperative cervical dilatation of > or = 8 mm. The mean baseline cervical dilatation for 400 microg and 200 microg misoprostol was 8.2 mm and 6.0 mm respectively (P < 0.001). The use of 400 mg misoprostol with an evacuation interval of two hours appears to be the optimal dosage and evacuation interval. Increasing the time interval beyond two hours did not confer any additional advantage on the rate of successful cervical dilatation but was instead associated with an increased incidence of side effects such as preoperative vaginal bleeding, abdominal pain and shivering.\n Our study has shown that Sublingual administration of 400 microg of misoprostol at least two hours before procedure is effective for preoperative cervical dilatation before vacuum aspiration in first trimester pregnancy termination. There is no additional advantages of increasing the dosing interval upto three hours.", "This study was undertaken to compare the effectiveness of mifepristone orally administered at 24 or 48 hours before first-trimester vacuum aspiration abortion with that of vaginally administered misoprostol as a cervical priming agent.\n In a randomized comparative trial 90 women who requested surgical termination of pregnancy were randomly assigned to receive 200 mg mifepristone orally 24 or 48 hours before the operation or 800 microg misoprostol vaginally 2 to 4 hours before the operation. The main outcome measures were baseline cervical dilatation, cumulative force required to dilate the cervix to 9 mm, and intraoperative blood loss.\n The baseline cervical dilatation was significantly greater among women who received mifepristone 48 hours before the operation (P =.02). This group also required the least mechanical force to dilate the cervix (P =.06). There were no significant differences among the 3 groups in the intraoperative blood loss, in the operating time, or in patient acceptability. Side effects such as hot flushes and headaches were significantly higher among women who received mifepristone 24 or 48 hours before the operation than among those who received misoprostol (P =.01 and P =. 002, respectively).\n Mifepristone is an effective cervical priming agent when orally administered 48 hours before vacuum aspiration for termination of first-trimester pregnancy. Because of its cost and availability in comparison with misoprostol, however, selective use may have to be considered.", "This study was undertaken to determine whether buccal misoprostol improves cervical preparation achieved with laminaria before second-trimester dilation and evacuation procedures.\n A randomized, double blind, placebo-controlled trial of preoperative cervical preparation with overnight laminaria and either buccal placebo or 400 microg buccal misoprostol approximately 90 minutes before second-trimester surgical abortion. Block randomization was used to provide balanced enrollment into 2 separate gestational age study groups: early (13-15(6/7)) and mid (16-20(6/7)) second trimester. Surgeons tested maximal cervical dilation by inserting the largest dilator that could be passed through the cervical os without force. Subject demographics and preprocedure symptoms were tracked.\n Groups were similar in regard to age, gravity, parity, delivery type, and gestational age. Data were analyzed from 125 women in the 13 to 15(6/7) (30 misoprostol, 32 placebo) and 16 to 20(6/7) (31 misoprostol, 32 placebo) gestational age groups. Overall, misoprostol treatment did not improve the initial mean dilation achieved with laminaria alone in either the 13 to 15(6/7) (46.0 fr +/- 5.0; placebo 45.0 fr +/- 6.2, P = .68) or 16 to 20(6/7) (50.9 fr +/- 5.6, placebo 48.9 fr +/- 5.2, P = .16) groups. However, a subanalysis of gestations 19 weeks or more demonstrated significantly greater dilation in the misoprostol group (53.6 fr fr +/- 5.3, placebo 48.5 fr +/- 5.0, P = .01). Subjects receiving misoprostol reported significantly more cramping than those receiving placebo (13-15(6/7) weeks misoprostol 25/30, 83%; placebo 17/32, 53%, P = .02; 16-20(6/7) week misoprostol 25/31, 81%, placebo 16/32, 50%, P = .02).\n Cervical dilation with laminaria is augmented by 400 microg buccal misoprostol in gestations 19 weeks or more, but not in earlier gestations. Misoprostol causes more abdominal cramping.", "To compare intravaginal misoprostol to prostaglandin (PG) E2 for cervical ripening in women with premature rupture of the membranes (PROM) after 34 weeks of gestation.\n Women with PROM after 34 weeks of gestation and an unripe cervix were randomized to receive PGE2 (2.5 mg) or misoprostol (50 microg). Both agents were placed intravaginally immediately after randomization, and the dose was repeated 6 hours later if necessary. After another 6 hours from the second insertion, oxytocin treatment was started if labor had not begun. Forty patients in each group were required to show a 30% improvement in delivery within 12 hours in the misoprostol group.\n One hundred nine patients were randomized; 54 were assigned to misoprostol and 55 to PGE2. Important demographic and clinical characteristics were similar between the groups. The mean time from first insertion to delivery was 16.4 hours in the misoprostol group and 22.0 hours in the PGE2 group. A second dose was required less frequently in the misoprostol group (22% vs 62% in the PGE2 group), and the percentage of patients delivered within 12 hours was higher in the misoprostol group (41% vs 16%). Tachysystole occurred in 20% and 6% of women in the misoprostol and PGE2 groups, respectively. Hyperstimulation occurred in 9% and 0%, and cesarean delivery in 19% and 26% of women in the misoprostol and PGE2 groups, respectively. Neonatal outcome was similar between groups.\n Intravaginal misoprostol is more effective than local PGE2 application to treat PROM after 34 weeks of gestation, but tachysystole occurs more commonly with misoprostol.", "To compare the efficacy and tolerability of sublingual misoprostol with those of intramuscular 15-methyl-prostaglandin F2alpha (15-M-PG F2alpha) for cervical dilation prior to vacuum aspiration (VA) in first-trimester pregnancy termination.\n Sixty pregnant women requesting pregnancy termination between the 9th and 12th week were randomized to receive 400 microg of sublingual misoprostol or an intramuscular injection of 125 microg of 15-M-PG F2alpha 2 h prior to vacuum aspiration. Baseline cervical dilation prior to vacuum aspiration was measured using Hegar's dilators. Other variables assessed included procedure duration, intraoperative blood loss, and associated adverse effects. Patient acceptability was assessed by questionnaires completed at the time of discharge from the hospital.\n Mean cervical dilation at vacuum aspiration was significantly greater in the misoprostol group than in the 15-M-PG F2alpha group (8.8 vs. 7.6 mm; P<0.01), and preoperative adverse effects were significantly less frequent in the sublingual misoprostol group (P<0.05). However, procedure duration and intraoperative blood loss were similar in both groups. The acceptability rates were 93.3% in the sublingual misoprostol group and 76.6% in the 15-M-PG F2alpha group, respectively; however, 6.6% patients in the sublingual misoprostol group thought that the tablets had an unpleasant taste.\n Sublingual misoprostol appears to be an effective alternative to intramuscular 15-M-PG F2alpha for cervical dilation prior to vacuum aspiration in first trimester pregnancy. In addition, misoprostol is inexpensive and convenient to use and has higher patient acceptability rates." ]	Cervical preparation with osmotic dilators and/or misoprostol before second-trimester D&E is safe and effective. Osmotic dilators appear to provide superior cervical dilation when compared to prostaglandins alone or when combined with prostaglandins, however this difference in cervical dilation does not appear to result in differences in procedure time or complication rates. There does not appear to be clear clinical benefit from two days of cervical preparation compared to one-day prior to second-trimester D&E below 19 weeks gestational duration. Mifepristone plus misoprostol was associated with high rates of pre-procedural expulsions and does not appear to be a useful method of cervical preparation before second-trimester dilation and evacuation. Same-day procedures appear to be a safe and reasonable option in the early second trimester, however, more research is needed to assess the effectiveness and safety of same-day procedures in the later second trimester.
CD000016	[ "10717757", "12788572", "7866044", "15850631", "8698011", "3544892", "2190705", "18575626", "11681222", "15040556", "3048759", "15567011", "6141423", "17046467", "15189457", "1812599", "17570848", "17519410", "19128455", "10929148", "17519010", "8311568", "11044276", "8684102", "11502317", "17990228" ]	[ "Amodiaquine remains effective for treating uncomplicated malaria in west and central Africa.", "Effect of intermittent treatment with amodiaquine on anaemia and malarial fevers in infants in Tanzania: a randomised placebo-controlled trial.", "[Parasitological and clinical response to amodiaquine versus chloroquine in the treatment of Plasmodium falciparum malaria in children in an endemic area].", "Amodiaquine alone, amodiaquine+sulfadoxine-pyrimethamine, amodiaquine+artesunate, and artemether-lumefantrine for outpatient treatment of malaria in Tanzanian children: a four-arm randomised effectiveness trial.", "A randomised controlled trial to assess the relative efficacy of chloroquine, amodiaquine, halofantrine and Fansidar in the treatment of uncomplicated malaria in children.", "Amodiaquine less effective than chloroquine in the treatment of falciparum malaria in the Philippines.", "[Uncomplicated malaria attack in an area with high chloroquine resistance. 2. Evaluation of first-choice therapeutic scheme].", "An open label, randomised trial of artesunate+amodiaquine, artesunate+chlorproguanil-dapsone and artemether-lumefantrine for the treatment of uncomplicated malaria.", "[Evaluation of efficacy and tolerance of amodiaquine versus chloroquine in the treatment of uncomplicated malaria outbreak in children of Gabon].", "Efficacy of chloroquine, amodiaquine, sulphadoxine-pyrimethamine and combination therapy with artesunate in Mozambican children with non-complicated malaria.", "Effectiveness of amodiaquine, sulfadoxine-pyrimethamine, and combinations of these drugs for treating chloroquine-resistant falciparum malaria in Hainan Island, China.", "Combination treatments for uncomplicated falciparum malaria in Kampala, Uganda: randomised clinical trial.", "Effectiveness of amodiaquine as treatment for chloroquine-resistant Plasmodium falciparum infections in Kenya.", "Efficacy, safety, and tolerability of amodiaquine plus sulphadoxine-pyrimethamine used alone or in combination for malaria treatment in pregnancy: a randomised trial.", "[Efficacy of therapeutic combinations with artemisinin derivatives in the treatment of non complicated malaria in Burundi].", "Falciparum malaria fully cleared by amodiaquine, pyrimethamine-sulfadoxine and pyrimethamine-sulfalene in areas of chloroquine resistance in Dodoma, Tanzania.", "Efficacy and tolerability of four antimalarial combinations in the treatment of uncomplicated Plasmodium falciparum malaria in Senegal.", "Combination therapy for uncomplicated falciparum malaria in Ugandan children: a randomized trial.", "Artemisinin-based combinations versus amodiaquine plus sulphadoxine-pyrimethamine for the treatment of uncomplicated malaria in Faladje, Mali.", "In vivo efficacy study of amodiaquine and sulfadoxine/ pyrimethamine in Kibwezi, Kenya and Kigoma, Tanzania.", "Randomized clinical trial of artemisinin versus non-artemisinin combination therapy for uncomplicated falciparum malaria in Madagascar.", "Resistance of Plasmodium falciparum to antimalarial drugs in Equatorial Guinea.", "Chemoresistance of Plasmodium falciparum in the urban region of Yaounde, Cameroon. Part 2: Evaluation of the efficacy of amodiaquine and sulfadoxine-pyrimethamine combination in the treatment of uncomplicated Plasmodium falciparum malaria in Yaounde, Cameroon.", "Atovaquone and proguanil for Plasmodium falciparum malaria.", "Amodiaquine, sulfadoxine/pyrimethamine, and combination therapy for treatment of uncomplicated falciparum malaria in Kampala, Uganda: a randomised trial.", "Randomized comparison of amodiaquine plus sulfadoxine-pyrimethamine, artemether-lumefantrine, and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Burkina Faso." ]	[ "Many countries in Africa are now confronted with the dilemma of shifting drug policies for uncomplicated falciparum malaria from chloroquine, which has become largely ineffective, to a new first-line drug and amodiaquine is one of the possible options. A multicentre, open-label randomized controlled trial of amodiaquine 30 mg/kg vs chloroquine 25 mg/kg over 3 days was performed in Senegal, Cameroon, Gabon, and Burkina Faso between 1996 and 1998 and patients were followed-up for 14 days. Sensitivity of isolates in vitro and whole blood levels of chloroquine and amodiaquine were also measured. The primary efficacy parameter was parasitological clearance on day 14 (parasitological success). The secondary efficacy parameter was absence of signs/symptoms of malaria on day 14 (clinical success). Among the 364 patients randomized and receiving the assigned treatment (chloroquine n = 185, amodiaquine n = 179), 137 and 139, respectively, reached the primary endpoint. Amodiaquine proved significantly more effective than chloroquine. The summary odds ratio (95% CI) was 7.79 (4.54-13.35) for parasitological success, and 6.3 (3.4-11.68) for clinical success. Sensitivity in vitro and chloroquine blood levels were good predictors of chloroquine failure. Amodiaquine remains effective for treating uncomplicated falciparum malaria in areas of West and Central Africa where chloroquine resistance is prevalent. However, measures should be taken to protect the lifespan of amodiaquine where the drug is introduced for use.", "Malaria is a major cause of infant morbidity and mortality in sub-Saharan Africa, and is often complicated by severe anaemia. Resistance of Plasmodium falciparum to most affordable antimalarial drugs is an impediment to intermittent chemotherapy. We investigated the effect of presumptive intermittent treatment with amodiaquine and daily iron supplementation in infants on malarial fevers and anaemia, in a holoendemic area of Tanzania where malaria is largely resistant to chloroquine and sulfadoxine/ pyrimethamine.\n 291 infants aged 12-16 weeks who attended three clinics were randomised to receive amodiaquine, iron supplementation, amodiaquine plus iron supplementation, or placebo. Over 6 months, we gave amodiaquine three times with intervals of 60 days; oral iron supplementation was given daily. Malarial fevers and anaemia were monitored at bimonthly treatment visits and by self-reporting to health centres.\n The protective efficacy of intermittent amodiaquine treatment in prevention of malarial fevers and anaemia was 64.7% (95% CI, 42.4-77.2) and 67.0% (95% CI, 34.5-83.4), respectively. Protective efficacy was similar in the group receiving amodiaquine plus iron supplementation. Infants receiving iron supplementation only were partly protected against anaemia (protective efficacy 59.8%; 95% CI, 23.4-78.9), but not against malarial fevers. 4 months' follow-up did not show rebound morbidity. We noted no haematological or clinical adverse effects.\n Presumptive intermittent treatment for malaria with amodiaquine reduced malarial fevers and anaemia in infants, in an area with high resistance to other antimalarials. Intermittent treatment strategies for malaria in highly endemic areas could be of great benefit to public health.", "The therapeutic management of malaria in endemic regions is now hampered not only by the limited number of antimalarial agents, but also by the appearance of chemoresistant plasmodial strains and by the sometimes severe adverse effects related to the use of some of these drugs. Between January and July 1993, 100 patients presenting with symptomatic Plasmodium falciparum malaria were randomised to receive amodiaquine or chloroquine at the dose of 30 mg/kg for 3 days. The objective of this study was to compare the efficacy and safety of these two 4-aminoquinolines in the treatment of uncomplicated malaria. The parasite clearance was 4.87 (+/- 0.33) days in the amodiaquine group and 5.55 (+/- 0.31) days in the chloroquine group. All subjects in both groups were afebrile by D7. Cutaneous adverse effects, such as pruritus, were reported with both amodiaquine (3.2%) and chloroquine (6.8%). Amodiaquine was found to be significantly more effective than chloroquine in terms of parasite clearance on D7. The therapeutic failure rate was 0% for amodiaquine versus 16.3% for chloroquine. At a time when chemoresistance of Plasmodium falciparum, especially chloroquine-resistance, has spread to malarial endemic zones, amodiaquine should be very widely indicated in the treatment of simple malaria due to its excellent efficacy and good safety.", "Many countries in Africa are considering a change to combination treatment for falciparum malaria because of the increase in drug resistance. However, there are few effectiveness data for these combinations. Our aim was to study the effectiveness of three drug combinations that have proven efficacious in east Africa compared with amodiaquine monotherapy.\n We undertook a randomised trial of antimalarial drug combinations for children (aged 4-59 months) with uncomplicated malaria in Muheza, Tanzania, an area with a high prevalence of resistance to sulfadoxine-pyrimethamine and chloroquine. Children were randomly allocated 3 days of amodiaquine (n=270), amodiaquine +sulfadoxine-pyrimethamine (n=507), or amodiaquine+artesunate (n=515), or a 3-day six-dose regimen of artemether-lumefantrine (n=519). Drugs were taken orally, at home, unobserved by medical staff. The primary endpoint was parasitological failure by day 14 assessed blind to treatment allocation. Secondary endpoints included day 28 follow-up and gametocyte carriage. Analysis was by intention to treat.\n Of 3158 children screened, 1811 were randomly assigned treatment and 1717 (95%) reached the 14-day follow-up. The amodiaquine group was stopped early by the data and safety monitoring board. By day 14, the parasitological failure rates were 103 of 248 (42%) for amodiaquine, 97 of 476 (20%) for amodiaquine+sulfadoxine-pyrimethamine, 54 of 491 (11%) for amodiaquine+artesunate, and seven of 502 (1%) for artemether-lumefantrine. By day 28, the parasitological failure rates were 182 of 239 (76%), 282 of 476 (61%), 193 of 472 (40%), and 103 of 485 (21%), respectively. The difference between individual treatment groups and the next best treatment combination was significant (p<0.001) in every case. Recrudescence rates by day 28, after correction by genotyping, were 48.4%, 34.5%, 11.2%, and 2.8%, respectively.\n The study shows how few the options are for treating malaria where there is already a high level of resistance to sulfadoxine-pyrimethamine and amodiaquine. The WHO-packaged six-dose regimen of artemether-lumefantrine is effective taken unsupervised, although cost is a major limitation.", "A randomised controlled trial was carried out to determine the relative efficacy of four commonly used antimalarial drugs in children aged three to twelve years presenting with uncomplicated malaria at the Eldoret District Hospital, Kenya. One hundred and eighty eight children were studied between July 1993 and July 1994. There were no significant baseline differences between treatment groups with respect to age, sex, weight, ethnicity, haemoglobin, white blood cell (WBC) counts, parasite counts, previous exposure to malaria and prior treatment. Of the 188 patients, eleven were lost to follow-up while twelve were discontinued from the study due to poor clinical response. Most of the latter (eight out of twelve) were in the chloroquine group. By day seven, there were significant differences (p = 0.004) in parasite clearance between groups. There were no significant statistical differences between the groups (p = 0.12) with regard to the fever clearance time. However, there was a significant statistical difference (p = 0.00003) between the treatment groups in the cure rates. Halofantrine was the most efficacious drug with 82% of the cases cured followed by fansidar(R)(62%), amodiaquine (55%) and chloroquine (29%). RI and RII resistance were observed in all the treatment groups, i.e. halofantrine (18%), fansidar (38%), amodiaquine (45%) and chloroquine (67%) while RIII resistance was only observed in the chloroquine group(3%).", "Amodiaquine was compared to chloroquine in two groups of Filipino patients with uncomplicated falciparum malaria. Every patient received 25 mg/kg of base orally given over three days. In a hospital study, all eight patients receiving chloroquine cleared their parasitemia by day 6, but six of eight patients receiving amodiaquine failed to clear parasitemia and in four patients there was no response at all (RIII resistance); this difference was significant (P less than 0.01). In a village based study, there was initial clearing of parasitemia in each patient. However, recrudescent infection occurred in all five patients receiving amodiaquine (RI resistance). Five of six falciparum infections were sensitive to chloroquine, while parasitemia reappeared in one patient. In this village, resistance to amodiaquine was significantly more common than resistance to chloroquine (P less than 0.05). To our knowledge, this is the first report of amodiaquine being substantially worse than chloroquine in the treatment of Plasmodium falciparum infection.", "The authors evaluate the comparative efficiency of chloroquine and amodiaquine (35 mg/kg during 3 days) for uncomplicated malaria treatment in an area with high chemoresistance level. 236 patients with malaria were examined and treated. 38% of them previously used antimalarials. The increase dosage in comparison with the WHO recommendations (25 mg/kg), lead to no advantages for chloroquine treatment (50% failure), in contrast with amodiaquine (4% failure). Therefore amodiaquine might be preferred in the health field unit for uncomplicated malaria.", "Artesunate+amodiaquine (AS+AQ) and artemether-lumefantrine (AL) are now the most frequently recommended first line treatments for uncomplicated malaria in Africa. Artesunate+chlorproguanil-dapsone (AS+CD) was a potential alternative for treatment of uncomplicated malaria. A comparison of the efficacy and safety of these three drug combinations was necessary to make evidence based drug treatment policies.\n Five hundred and thirty-four, glucose-6-phosphate dehydrogenase (G6PD) normal children were randomised in blocks of 15 to the AS+AQ, AL or AS+CD groups. Administration of study drugs was supervised by project staff and the children were followed up at r home on days 1,2,3,7,14 and 28 post treatment. Parasitological and clinical failures and adverse events were compared between the study groups.\n In a per-protocol analysis, the parasitological and clinical failure rate at day 28 post treatment (PCF28) was lower in the AS+AQ group compared to the AL or AS+CD groups (corrected for re-infections: 6.6% vs 13.8% and 13.8% respectively, p = 0.08; uncorrected: 14.6% vs 27.6% and 28.1% respectively, p = 0.005). In the intention to treat analysis, the rate of early treatment failure was high in all three groups (AS+AQ 13.3%; AL 15.2%; and AS+CD 9.3%, p = 0.2) primarily due to vomiting. However, the PCF28 corrected for re-infection was lower, though not significantly, in the AS+AQ group compared to the AL or the AS+CD groups (AS+AQ 18.3%; AL 24.2%; AS+CD 20.8%, p = 0.4) The incidence of adverse events was comparable between the groups.\n AS+AQ is an appropriate first line treatment for uncomplicated malaria in Ghana and possibly in the neighbouring countries in West Africa. The effectiveness of AL in routine programme conditions needs to be studied further in West Africa.\n ClinicalTrials.gov NCT00119145.", "We conducted a prospective study from September 1997 to January 1998 in Libreville (Gabon). Fifty-three (53) children with uncomplicated P. falciparum malaria were included and divided into two groups. The first group (27 patients) was treated with amodiaquine and the second (26 patients) with chloroquine. The efficacy and tolerance of amodiaquine 30 mg/kg base over 3 days (10 mg/kg daily) and chloroquine 25 mg/kg base over 3 days (10 mg/kg day 0, 10 mg/kg day 1, 5 mg/kg day 3) were estimated at days 7 and 14. Clinical examination and parasitaemia were assessed on days 0, 1, 2, 3, 7, 14. Haematological and biochemical parameters were determined on days 0 and 7. Amodiaquine was shown to be more effective than chloroquine in clinical response and ridding patients of parasites: adequate clinical response was significantly higher with amodiaquine than chloroquine [100% (27/27) versus 45% (9/20), p < 0.0005]. Rates for early treatment failure (ETF) and late treatment failure (LTF) were respectively 35% and 12% with chloroquine. The parasitological success rate was significantly higher with amodiaquine than chloroquine on days 7 [93% (25/27) versus 62% (13/21), p < 0.008] and 14 [100% (13/13) versus 44% (4/9), p < 0.01]. The RI resistance type was 7% in the amodiaquine group. The rate of in vivo chloroquino-resistance was 53%, essentially of RII and RIII type. Overall, the two drugs were well tolerated.", "This paper reports a two-phase study in Manhiça district, Mozambique: first we assessed the clinical efficacy and parasitological response of Plasmodium falciparum to chloroquine (CQ), sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ), then we tested the safety and efficacy in the treatment of uncomplicated malaria, of three combinations: AQ + SP, artesunate (AR) + SP and AQ + AR. Based on the WHO (1996, WHO/MAL/96.1077) in vivo protocol, we conducted two open, randomized, clinical trials. Children aged 6-59 months with axillary body temperature > or = 37.5 degrees C and non-complicated malaria were randomly allocated to treatment groups and followed up for 21 days (first and second trial) and 28 days (first trial). The therapeutic efficacy of AQ (91.6%) was better than that of SP (82.7%) and CQ (47.1%). After 14 days, 69% of the strains were parasitologically resistant to CQ, 21.4% to SP and 26% to AQ. Co-administration of AQ + SP, AR + SP and AQ + AR was safe and had 100% clinical efficacy at 14-day follow-up. The combination therapies affected rapid fever clearance time and reduced the incidence of gametocytaemia during follow-up.", "The study was carried out in 1985-86 in Hainan Island where Plasmodium falciparum is resistant to chloroquine. Fifty cases of falciparum malaria were treated with 1800 mg amodiaquine for 3 days: the cure rate was 65.3%, and the mean time to clear fever and asexual parasitaemia was 30.7 and 60.3 hours, respectively; 34.7% of cases showed RI or RII recrudescence, and one patient's temperature did not come down to normal within 7 days.Twenty-one cases were treated with sulfadoxine-pyrimethamine (1500 mg and 75 mg, respectively): 19 were cured, I showed RI and another had an S or RI response; the mean time for fever control was 56.1 hours.Fifty cases were treated with amodiaquine plus sulfadoxine and 49 received amodiaquine plus sulfadoxine-pyrimethamine: the cure rate was 97.9% and 100%, respectively; the mean time for fever clearance was 25.0 and 25.7 hours and for parasite clearance 57.1 and 52.8 hours, respectively. These drug combinations gave much better results for cure and for symptom control than amodiaquine or sulfadoxine-pyrimethamine alone, and may be considered for treatment of chloroquine-resistant falciparum malaria.", "Plasmodium falciparum resistance has rendered chloroquine monotherapy ineffective in much of Africa, but data on alternative regimens are limited. We compared chloroquine+sulfadoxine-pyrimethamine, amodiaquine+sulfadoxine-pyrimethamine, and amodiaquine+artesunate for treatment of uncomplicated malaria in Kampala, Uganda.\n Of 1017 consecutive patients aged 6 months to 10 years with uncomplicated malaria who were screened, 418 were randomised to receive: chloroquine (25 mg/kg over 3 days) and sulfadoxine-pyrimethamine (25 mg/kg sulfadoxine, 1.25 mg/kg pyrimethamine, single dose); amodiaquine (25 mg/kg over 3 days) and sulfadoxine-pyrimethamine; or amodiaquine and artesunate (4 mg/kg daily for 3 days). Primary efficacy outcomes were 28-day clinical failure risks, adjusted and unadjusted by genotyping to distinguish new infection and recrudescence. The primary safety endpoint was incidence of serious adverse events during follow-up. Analysis was intention to treat and per protocol.\n 18 patients were excluded before enrollment. Of those enrolled, 384 of 400 (96%) were assigned an efficacy outcome and 396 (99%) were assessed for safety. Risk of 28-day clinical treatment failure was significantly higher with chloroquine+sulfadoxine-pyrimethamine (44/125 [35%]) than with amodiaquine+sulfadoxine-pyrimethamine (12/129 [9%]; risk difference 26% [95% CI 16-36]; p<0.0001) or amodiaquine+artesunate (3/130 [2%]; 33% [24-42]; p<0.0001). The greater risk of clinical treatment failure with amodiaquine+sulfadoxine-pyrimethamine was balanced by a lower risk of new infection, resulting in a similar need for retreatment over 28 days for amodiaquine+sulfadoxine-pyrimethamine (17/129 [13%]) and amodiaquine+artesunate (16/130 [12%]; p=0.854). Serious adverse events were uncommon with all regimens.\n Risk of treatment failure with chloroquine+sulfadoxine-pyrimethamine was unacceptably high. Combinations of amodiaquine and sulfadoxine-pyrimethamine or artesunate were significantly more efficacious, and each regimen could be an appropriate alternative for treatment of uncomplicated malaria in Africa.", "Studies were conducted in Malindi, Kenya, to assess the response of Plasmodium falciparum to chloroquine and amodiaquine in vivo (by an extended 14-day test) and in vitro (with the Rieckmann micro test). In-vivo resistance was demonstrated in 19 of 69 (28%) infections treated with chloroquine, but in only 2 of 60 (3.3%) of those treated with amodiaquine (p less than 0.001). In-vitro resistance to chloroquine was demonstrated in 15 of 23 (65%) tests. In contrast, 22 of the same 23 isolates were sensitive to amodiaquine in vitro. Effective concentrations by probit analysis for 50% and 99% (EC50 and EC99) inhibition, respectively, were 180.7 and 4319.6 nmol/l for chloroquine and 12.2 and 147.0 nmol/l for amodiaquine. The results suggest that amodiaquine is effective for the treatment of chloroquine-resistant falciparum malaria in Kenya.", "The widespread increase in resistance of Plasmodium falciparum to chloroquine and sulphadoxine-pyrimethamine threatens the use of these drugs for malaria treatment in pregnancy. We aimed to assess the safety and efficacy of amodiaquine alone or in combination with sulphadoxine-pyrimethamine as alternative regimens.\n Pregnant women with a gestational age of 16 weeks or more who attended antenatal clinics at a district hospital in Ghana were screened for malaria with OptiMAL dipsticks. 900 pregnant women who had a positive test result and P falciparum asexual stage parasitaemia were enrolled and randomly assigned chloroquine, sulphadoxine-pyrimethamine, amodiaquine, or amodiaquine plus sulphadoxine-pyrimethamine. The primary outcome was parasitological failure by day 28 of treatment. Women were seen on days 3, 7, 14, and 28 after the start of treatment to assess the effect of treatment on peripheral parasitaemia, haemoglobin concentration, white-blood-cell count, and liver function. Additionally, reports of adverse effects were solicited and monitored during follow-up visits. Analysis was by intention to treat. This trial is registered with the US National Institute of Health clinical trials database number NCT00131703.\n PCR-corrected parasitological failure by day 28 was 14%, 11%, 3%, and 0% in the women assigned chloroquine, sulphadoxine-pyrimethamine, amodiaquine, and amodiaquine plus sulphadoxine-pyrimethamine, respectively (p<0.0001). No serious liver toxic effects or white-blood-cell dyscrasias were noted. Minor side-effects were reported more often on day 3 by women receiving amodiaquine (86%) or amodiaquine plus sulphadoxine-pyrimethamine (90%) than those receiving sulphadoxine-pyrimethamine (48%) or no antimalarial drugs (34%; p<0.0001 for every comparison).\n Amodiaquine alone or in combination with sulphadoxine-pyrimethamine, although associated with minor side-effects, is effective when used to treat malaria in pregnancy.", "Faced with the problem of resistance to chloroquine and sulfadoxine-pyrimethamine, the Ministry of Public Health of Burundi decided to study the efficacy of two artemisinin-based combinations, the fixed combination of artemether-lumefantrine and the combination of amodiaquine + artesunate. The efficacy of these combinations for the treatment of uncomplicated falciparum malaria was studied in two sites representative of the country, in Kigobe neighbourhood of Bujumbura, the capital city, and in Buhiga, a rural area. The study followed the standardized WHO protocol from October 2001 to November 2002. A total of 295 children under 5 years were included; 153 children were treated with artesunate and amodiaquine (77 at Buhiga and 76 at Kigobe), and 142 children with the combination of artemether-lumefantrine (64 at Buhiga and 78 at Kigobe). Among the 295 children, 290 were followed up to 14 days. In the group of 149 children treated with artesunate and amodiaquine, 142 (95.3%, 95% CI: 91.9-98.7%) presented with adequate clinical and parasitological response, five (3.3%) with late parasitological failure, one (0.7%) with late clinical failure and one (0.7%) with early treatment failure. Among the 141 children treated with artemether-lumefantrine, 140 (99.3%, 95% CI: 97.9-100%) presented with adequate clinical and parasitological response and one (0.7%) with late parasitological failure at Buhiga. Side-effects were comparable in both groups except for the vomiting. Vomiting was more frequent in the artesunate + amodiaquine on D1 and D2. Both treatments decreased the gametocyte carriage but without getting full clearance in all the patients. During a consensus workshop, the Ministry of Public Health agreed on the combination of artesunate and amodiaquine as the first line drug for the treatment of uncomplicated falciparum malaria in Burundi including epidemic outbreak.", "The in vivo response of Plasmodium falciparum to chloroquine, amodiaquine, pyrimethamine-sulfalene (MetakelfinR) and pyrimethamine-sulfadoxine (FansidarR) was assessed in Dodoma in 1988. Asymptomatic schoolchildren with pure P. falciparum infection were given full curative doses of one of the above antimalarials. Daily parasitological follow-ups were made for seven days. Overall successful follow-up cases were 101, 108, 95 and 97 on chloroquine, amodiaquine, MetakelfinR and FansidarR respectively. The overall resistance rate in the area was 28%. Most of the resistant cases were RII type. There was only one case of MetakelfinR resistance. Amodiaquine and FansidarR were fully effective in eliminating asexual parasitaemia from the blood in all the cases during the seven days of follow-up. The results indicate that chloroquine, a commonly used antimalarial in Tanzania, is not as effective as amodiaquine, a less used drug. Although the 'antifols' are still highly effective in Tanzania, their potency could change with continued use. These drugs should, therefore, be protected and used judiciously.", "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.", "Combination therapy is now widely advocated as first-line treatment for uncomplicated malaria in Africa. However, it is not clear which treatment regimens are optimal or how to best assess comparative efficacies in highly endemic areas.\n To compare the efficacy and safety of 3 leading combination therapies for the treatment of uncomplicated malaria.\n Single-blind randomized clinical trial, conducted between November 2004 and June 2006, of treatment for all episodes of uncomplicated malaria in children in an urban community in Kampala, Uganda. A total of 601 healthy children (aged 1-10 years) were randomly selected and were followed up for 13 to 19 months, receiving all medical care at the study clinic.\n Study participants were randomized to receive 1 of 3 combination therapies (amodiaquine plus sulfadoxine-pyrimethamine, amodiaquine plus artesunate, or artemether-lumefantrine) when diagnosed with their first episode of uncomplicated malaria. The same assigned treatment was given for all subsequent episodes.\n 28-Day risk of parasitological failure (unadjusted and adjusted by genotyping to distinguish recrudescence from new infection) for each episode of uncomplicated malaria treated with study drugs.\n Of enrolled children, 329 of 601 were diagnosed with at least 1 episode of uncomplicated malaria, and 687 episodes of Plasmodium falciparum malaria were treated with study drugs. The 28-day risk of treatment failure (unadjusted by genotyping) for individual episodes of malaria were 26.1% (95% CI, 21.1%-32.1%) for amodiaquine plus sulfadoxine-pyrimethamine, 17.4% (95% CI, 13.1%-23.1%) for amodiaquine plus artesunate, and 6.7% (95% CI, 3.9%-11.2%) for artemether-lumefantrine (P<.05 for all pairwise comparisons). When only recrudescent treatment failures were considered, the risks of failure were 14.1% (95% CI, 10.3%-19.2%), 4.6% (95% CI, 2.5%-8.3%), and 1.0% (95% CI, 0.3%-4.0%) for the same order of study drugs, respectively (P< or =.008 for all pairwise comparisons, except amodiaquine plus artesunate vs artemether-lumefantrine, P = .05). There were no deaths or cases of severe malaria. Significant reductions in anemia (9.3% [95% CI, 7.0%-12.0%] at enrollment vs 0.6% [95% CI, 0.1%-2.2%] during the last 2 months of follow-up; P<.001) and asymptomatic parasitemia (18.6% [95% CI, 15.5%-22.1%] at enrollment vs 2.3% [95% CI, 1.5%-3.5%] during the last 2 months of follow-up; P<.001) were observed according to routine testing.\n Artemether-lumefantrine was the most efficacious treatment for uncomplicated malaria in the study population. With all study regimens, the provision of prompt and reasonably effective facility-based treatment was associated with good outcomes in long-term health measures.\n isrctn.org Identifier: ISRCTN37517549.", "Because of the emergence of chloroquine resistance in Mali, artemether-lumefantrine (AL) or artesunate-amodiaquine (AS+AQ) are recommended as first-line therapy for uncomplicated malaria, but have not been available in Mali until recently because of high costs.\n From July 2005 to January 2006, a randomized open-label trial of three oral antimalarial combinations, namely AS+AQ, artesunate plus sulphadoxine-pyrimethamine (AS+SP), and amodiaquine plus sulphadoxine-pyrimethamine (AQ+SP), was conducted in Faladje, Mali. Parasite genotyping by polymerase chain reaction (PCR) was used to distinguish new from recrudescent Plasmodium falciparum infections.\n 397 children 6 to 59 months of age with uncomplicated Plasmodium falciparum malaria were enrolled, and followed for 28 days to assess treatment efficacy. Baseline characteristics were similar in all three treatment groups. The uncorrected rates of adequate clinical and parasitologic response (ACPR) were 55.7%, 90.8%, and 97.7% in AS+AQ, AS+SP, and AQ+SP respectively (p < 0.001); after PCR correction ACPR rates were similar among treatment groups: 95.4%, 96.9%, and 99.2% respectively (p = 0.17). Mean haemoglobin concentration increased across all treatment groups from Day 0 (9.82 +/- 1.68 g/dL) to Day 28 (10.78 +/- 1.49 g/dL) (p < 0.001), with the greatest improvement occurring in children treated with AQ+SP. On Day 2, the prevalence of parasitaemia was significantly greater among children treated with AQ+SP (50.8%) than in children treated with AS+AQ (10.5%) or AS+SP (10.8%) (p < 0.001). No significant difference in gametocyte carriage was found between groups during the follow-up period.\n The combination of AQ+SP provides a potentially low cost alternative for treatment of uncomplicated P. falciparum infection in Mali and appears to have the added value of longer protective effect against new infection.", "We conducted two randomized clinical trials to determine the in vivo efficacy of amodiaquine and sulfadoxine/pyrimethamine in treating Plasmodium falciparum malaria. Seventy-five patients under the age of 10 years in Kibwezi, Kenya, and 171 patients in Kigoma, Tanzania, were enrolled for treatment. Due to loss of eight patients in Kibwezi and 37 in Kigoma to follow-up, we used best and worst case scenarios for the parasitological response. The in vivo sensitivity of Plasmodium falciparum to amodiaquine was 75% (no loss to follow-up) in Kibwezi and ranged from 85% in the best to 65% in the worst case scenario in Kigoma. The sensitivity to sulfadoxine/pyrimethamine was 70% to 88% in Kibwezi and 65% to 89% in Kigoma. R1 resistance to amodiaquine was 22% in Kibwezi and varied from 6% in the best to 26% for the worst case scenario in Kigoma. The R1 resistance to sulfadoxine/pyrimethamine was 5% to 23% in Kibwezi and 2% to 26% in Kigoma. R2 resistance was 3% for amodiaquine and 7% for sulfadoxine/pyrimethamine in Kibwezi and 9% in Kigoma for each treatment group. There was no statistically significant difference between treatment groups at either study site, except for a slight difference in R1 resistance in the best case scenario, Kibwezi, in favour of S/P. Although both amodiaquine and sulfadoxine/pyrimethamine resistance seems to be increasing, these antimalarials are still effective in parasite clearance.", "Data concerning antimalarial combination treatment for uncomplicated malaria in Madagascar are largely lacking. Randomized clinical trial was designed to assess therapeutic efficacies of chloroquine (CQ), amodiaquine (AQ), sulphadoxine-pyrimethamine (SP), amodiaquine plus sulphadoxine-pyrimethamine combination (AQ+SP) and artesunate plus amodiaquine combination (AQ+AS).\n 287 children between 6 months and 15 years of age, with uncomplicated falciparum malaria, were enrolled in the study. Primary endpoints were the day-14 and day-28 risks of parasitological failure, either unadjusted or adjusted by genotyping.\n All treatment regimens, except for CQ treatment, gave clinical cure rates above 97% by day-14 and 92% by day-28 (PCR-corrected). AQ+SP was as effective as AQ+AS. The risk of new infection within the month after therapy was generally higher for AQ+AS than AQ+SP.\n These findings show that the inexpensive and widely available combination AQ+SP may be valuable in for the treatment of uncomplicated malaria in Madagascar and could have an important role in this country, where much of the drugs administered go to patients who do not have malaria.", "One hundred and sixty-six children from Equatorial Guinea, all under 10 years of age and with acute uncomplicated falciparum malaria, were randomly allocated to four groups and treated with one of the following regimens: chloroquine or amodiaquine (25 mg base/kg body weight over 3 days), quinine (8 mg/kg every 8 h for 3 or 5 days), and sulphadoxine-pyrimethamine (25-1.25 mg/kg, in one dose). The parasite clearance rates up to day 14 were 28% with chloroquine, 74% with amodiaquine, and 95% with quinine or sulphadoxine-pyrimethamine. The times required to clear asexual blood forms of Plasmodium falciparum in sensitive cases were 64, 70, 73 and 65 h, respectively. Although quinine and sulphadoxine-pyrimethamine are equally effective, quinine is recommended for treatment of multidrug-resistant malaria in paediatric patients, essentially because of the risk of serious reactions to sulpha drugs. Health providers are, however, encouraged to keep supplies of sulphadoxine-pyrimethamine as an option and to refer patients quickly, if required.", "The spread of chloroquine resistance or its stabilization at a high level calls for a change in the therapeutic strategy, including a possible replacement of chloroquine. We assessed and compared the efficacy of amodiaquine and sulfadoxine-pyrimethamine in Yaoundé. Of 140 adults and children > 5 years enrolled in the study, 59 in the amodiaquine and 58 in the sulfadoxine-pyrimethamine treatment group were followed until day 14. The efficacy of amodiaquine was 100%, whereas 12.1% of the patients treated with sulfadoxine-pyrimethamine responded with an early treatment failure. Side effects in both treatment groups were mild and did not require any specific treatment. We did in vitro drug assays for monodesethylamodiaquine (active metabolite of amodiaquine) and pyrimethamine and measured plasma levels of monodesethylamodiaquine, sulfadoxine, and pyrimethamine. Unlike amodiaquine, the results of the in vitro drug sensitivity test for pyrimethamine were not concordant with the clinical response. A wide inter-individual variation in the plasma drug levels was observed. Unlike chloroquine, the mean plasma concentrations did not vary with age. There was no significant difference in the plasma concentrations of sulfadoxine and pyrimethamine between patients responding with an adequate clinical response and those responding with treatment failure. Amodiaquine has several advantages over sulfadoxine-pyrimethamine combination and may be considered to be an effective drug in an endemic zone with a moderate level of chloroquine resistance.", "The increasing spread of multidrug-resistant Plasmodium falciparum malaria emphasises the urgent need for alternative treatment regimens. The objective of the study was to establish the efficacy of a novel drug combination. We compared a combination of atovaquone and proguanil with amodiaquine in the treatment of acute uncomplicated P falciparum malaria in Lambaréné, Gabon.\n 142 adults were randomly allocated either a combination treatment of atovaquone 1000 mg daily and proguanil 400 mg daily for 3 days or treatment with amodiaquine 600 mg on admission, 600 mg 24 h later, and 300 mg after a further 24 h. Symptoms and clinical signs were recorded and giemsa-stained thick blood smears were done every 12 h until patients had been symptom-free and aparasitaemic for 24 h. 126 patients were followed up for 28 days or until recrudescence.\n In the atovaquone plus proguanil group 62 (87%) of 71 patients were cured and only one had recrudescent infection. By contrast, the cure rate was significantly lower (p=0.022) with amodiaquine (51 [72%] of 71; there were 12 recrudescences in the amodiaquine group). Eight patients in each group were lost to follow-up. Patients treated with atovaquone plus proguanil complained of nausea (33%) and vomiting (29%), and the most commonly reported adverse effects of amodiaquine were pruritus (43%) and insomnia (27%).\n Atovaquone and proguanil was a highly effective and safe drug combination in patients with acute uncomplicated P falciparum malaria in Gabon.", "Increasing Plasmodium falciparum resistance to chloroquine in sub-Saharan Africa necessitates use of alternative antimalarial agents. Affordable alternative treatments include sulfadoxine/pyrimethamine and amodiaquine. Combination of antimalarial agents can increase therapeutic efficacy and delay emergence of drug resistance. We compared the efficacy of sulfadoxine/pyrimethamine, amodiaquine, and an amodiaquine/sulfadoxine/pyrimethamine combination for treatment of uncomplicated malaria in a region of high chloroquine resistance.\n Patients with symptoms of uncomplicated falciparum malaria and confirmed disease in Kampala, Uganda, were randomly assigned to receive sulfadoxine/pyrimethamine (25 mg/kg sulfadoxine, and 1.25 mg/kg pyrimethamine) plus placebo; amodiaquine (25 mg/kg) plus placebo; or amodiaquine plus sulfadoxine/pyrimethamine. Patients were followed up for 14 days, and clinical and parasitological outcomes were assessed.\n 90% (400/445) of patients enrolled in the study successfully completed 14 days of follow-up. Treatment failure based on clinical criteria occurred in 13 of 131 (10%) patients on sulfadoxine/ pyrimethamine, nine of 131 (7%) on amodiaquine, and four of 138 (3%) on amodiaquine/sulfadoxine/pyrimethamine. Based on parasitological criteria, treatment failed in 26%, 16%, and 10% of these patients, respectively. Amodiaquine/sulfadoxine/pyrimethamine was significantly more effective than sulfadoxine/pyrimethamine alone in children aged younger than 5 years (clinical failure in 3.5% vs 13.9%, respectively, risk difference 10.4% [95% CI, 1.6-19.3] p=0.021; parasitological failure in 12.8% vs 26.4%, risk difference 13.6% [1.2-26.0] p=0.041).\n Sulfadoxine/pyrimethamine, amodiaquine, and amodiaquine/sulfadoxine/pyrimethamine were all effective for treatment of uncomplicated falciparum malaria in Uganda. The amodiaquine/sulfadoxine/pyrimethamine combination was the most effective, and could be the optimum low-cost alternative to chloroquine in Africa.", "Combination antimalarial therapy is advocated to improve treatment efficacy and limit selection of drug-resistant parasites. We compared the efficacies of 3 combination regimens in Bobo-Dioulasso, Burkina Faso: amodiaquine plus sulfadoxine-pyrimethamine, which was recently shown to be highly efficacious at this site; artemether-lumefantrine, the new national first-line antimalarial regimen; and dihydroartemisinin-piperaquine (DP), a newer regimen.\n We enrolled 559 patients >or=6 months of age with uncomplicated Plasmodium falciparum malaria and randomized them to the 3 regimens. We analyzed the risk of recurrent parasitemia by day 28 and day 42, both unadjusted and adjusted by PCR methods to distinguish recrudescence and new infection.\n Complete data were available for 517 (92.5%) of the enrolled subjects. Early treatment failures occurred in 5 patients treated with amodiaquine plus sulfadoxine-pyrimethamine and in 2 patients each treated with the other regimens. The day 28 risk of recurrent parasitemia, unadjusted by genotyping, was significantly higher for patients receiving artemether-lumefantrine than for patients receiving amodiaquine plus sulfadoxine-pyrimethamine (20.1% vs. 6.2%; risk difference, 13.8%; 95% confidence interval, 7.0%-20.7%) or dihydroartemisinin-piperaquine (20.1% vs. 2.2%; risk difference, 17.9%; 95% confidence interval, 11.6%-24.1%). Similar differences were seen for children <5 years of age (54% of the study population) and when outcomes were extended to 42 days. Significant differences were not seen between outcomes for patients receiving amodiaquine plus sulfadoxine-pyrimethamine and outcomes for those receiving dihydroartemisinin-piperaquine. Recrudescences were uncommon (occurring in <5% of patients) in all treatment groups. No serious adverse events were noted.\n All regimens were highly efficacious in clearing infection, but considering the risks of recurrent malaria after therapy, the amodiaquine plus sulfadoxine-pyrimethamine and dihydroartemisinin-piperaquine regimens were more efficacious than the artemether-lumefantrine regimen (the new national regimen in Burkina Faso) for the treatment of uncomplicated P. falciparum malaria." ]	There is evidence to support the continued use of amodiaquine to treat uncomplicated malaria, although local drug resistance patterns need to be considered. Monitoring for adverse events should continue. This review summarizes trials up to 2003. For the reasons in the 'What's new' section, this review will no longer be updated.
CD001819	[ "9925837", "812052", "3082297", "20002013", "22664861", "3105304", "16027693" ]	[ "Feeding strategies for premature infants: randomized trial of gastrointestinal priming and tube-feeding method.", "Nasoduodenal versus nasogastric feeding in the very low birthweight infant.", "Nasogastric compared with nasoduodenal feeding in low birthweight infants.", "Slow versus rapid enteral feeding advancement in preterm newborn infants 1000-1499 g: a randomized controlled trial.", "Randomized controlled trial of slow vs rapid enteral feeding advancements on the clinical outcomes of preterm infants with birth weight 750-1250 g.", "Enteral feeding in very-low-birth-weight infants. A comparison of two nasogastric methods.", "Continuous feeding promotes gastrointestinal tolerance and growth in very low birth weight infants." ]	[ "Data on enteral feeding management of premature infants are limited and often not the subject of randomized clinical trials. Several small studies suggest benefits from the early initiation of feeding, but do not assess the combined effects of time of initiation of feeding, tube-feeding method, and type of milk used. Either singly or in combination, these treatments may affect growth, bone mineralization, biochemical measures of nutritional status, and feeding tolerance, and, ultimately, the duration of hospitalization.\n A total of 171 premature infants, stratified by gestational age (26 to 30 weeks) and diet (human milk or preterm formula) were assigned randomly among four treatment combinations in a balanced two-way design comparing the presence or absence of gastrointestinal (GI) priming for 10 days and continuous infusion versus intermittent bolus tube-feeding.\n The major outcome, time required for infants to attain full oral feeding, was similar among treatments. GI priming was not associated with any measured adverse effect and was associated with better calcium and phosphorus retention, higher serum calcium and alkaline phosphatase activity, and shorter intestinal transit times. The bolus tube-feeding method was associated with significantly less feeding intolerance and greater rate of weight gain than the continuous method. In addition, the greater the quantity of human milk fed, the lower the morbidity.\n Early GI priming with human milk, using the bolus tube-feeding method, may provide the best advantage for the premature infant.", "The practicality, effectiveness, and safety of feeding very low birthweight infants (less than 1,300 gm) by continuous nasoduodenal infusion was assessed by comparison with continuous nasogastric feeding. The nasoduodenal group appeared to have a clear advantage over the nasogastric group for the overall period in terms of caloric intake (131 cal/kg/day vs. 106 cal/kg/day), average weight gain (16 gm/day vs. 10 gm/day), and safety. This advantage was even more striking in the first two weeks of life. A caloric intake of 120 cal/kg/day could be reached within 48 to 72 hours after tube placement in the nasoduodenal group but only after a week in the nasogastric group. Nasoduodenal feeding resulted in faster weight gain than comparable published data on conventional feeding, peripheral intravenous alimentation, and parenteral alimentation. There were no cases of aspiration associated with tubes placed in the duodenum whereas two cases of aspiration pneumonia were associated with tubes placed in the stomach. With the tip of the catheter in the duodenum, none of the complications reported with nasojejunal tubes (intussusception, perforation, or necrotizing enterocolitis) were seen, either in the initial pilot study reported here or in 50 additional infants.", "One hundred successive infants weighing less than 1500 g at birth were allocated alternately to intermittent nasogastric or continuous nasoduodenal feeding regimens. Eighty were appropriate for gestational age, and of these 25 fed successfully by nasogastric tube and 16 tolerated nasoduodenal feeding until 1600 g. No significant differences in either calorie intake or growth rates were identified throughout the seven weeks of the study. Because of the increased complexity and radiological exposure involved with feeding transpylorically, nasogastric feeding may be preferred as a method of feeding the low birthweight infant.", "To evaluate whether preterm neonates weighing 1000-1499 g at birth receiving rapid enteral feeding advancement at 30 mL/kg/day attain full feedings (180 mL/kg/day) earlier than those receiving slow enteral feeding advancement at 20 mL/kg/day without increase in the incidence of feeding intolerance or necrotizing enterocolitis.\n A total of 100 stable intramural neonates weighing between 1000 and 1499 g and gestational age less than 34 weeks were randomly allocated to enteral feeding (expressed human milk or formula) advancement of 20 mL/kg/day (n = 50) or 30 mL/kg/day (n = 50). RESULTs: Neonates in the rapid feeding advancement group achieved full volume feedings before the slow advancement group (median 7 days vs. 9 days) (p < 0.001), had significantly fewer days of intravenous fluids (median 2 days vs. 3.4 days) (p < 0.001), shorter length of stay in hospital (median 9.5 days vs. 11 days) (p = 0.003) and regained birth weight earlier (median 16 days vs. 22 days) (p < 0.001). There were no statistical differences in the proportion of infants with apnea, feed interruption or feed intolerance.\n Rapid enteral feeding advancements of 30 mL/kg/day are well tolerated by stable preterm neonates weighing 1000-1499 g.", "To evaluate the effect of slow vs rapid rates of advancement of enteral feed volumes on the clinical outcomes in preterm infants with 750-1250 g birth weight.\n A total of 92 stable neonates 750-1250 g and gestational age <32 weeks were randomly allocated to enteral feeding advancement of 20 mL/kg/d (n = 46) or 30 mL/kg/d (n = 46). The primary outcome was days to reach full enteral feeding, defined as 180 mL/kg/d. Secondary outcomes included rates of necrotizing enterocolitis (NEC) and culture-proven sepsis, days of parenteral nutrition (PN), length of hospital stay, and growth end points.\n Neonates in the rapid-feeding advancement group achieved full enteral volume of feedings earlier than the slower advancement group. They received significantly fewer days of PN, exhibited a shorter time to regain birth weight, and had a shorter duration of hospital stay. The incidence of NEC and the number of episodes of feeding intolerance were not significantly different between the groups, whereas the incidence of culture-proven late-onset sepsis was significantly less in infants receiving a rapid feeding advancement. Excluding infants who were small for gestational age at birth, the incidence of extrauterine growth restriction was significantly reduced in the rapid-advancement group at 28 days and at hospital discharge.\n Rapid enteral feeding advancements in 750-1250 g birth weight infants reduce the time to reach full enteral feeding and the use of PN administration. Rapid-advancement enteral feed also decreases extrauterine growth restriction with improved short-term outcomes for these high-risk infants.", "Nutritional benefits and feeding-related complications were prospectively compared in 53 preterm very-low-birth-weight infants receiving isoenergetic feeding by either the continuous nasogastric (n = 30) or intermittent nasogastric (n = 23) route. Stepwise regression techniques were used to develop models relating feeding-associated factors. Feeding method significantly affected weight gain in infants 1000 to 1249 g birth weight with continuous nasogastric feeding associated with an additional weight gain of 3.6 to 6.1 g/kg/d. No effects of feeding method on changes in occipitofrontal circumference, triceps skin-fold thickness, bilirubin values, or total protein values were demonstrable. There were few major differences between feeding groups on measures of feeding complications. Continuous nasogastric feeding was fairly well tolerated and resulted in improved weight gain when compared with intermittent nasogastric feeding in preterm infants 1000 to 1249 g birth weight.", "To compare the effects of continuous versus intermittent feeding on gastrointestinal tolerance and growth in very low birth weight (VLBW) infants.\n In a randomized, controlled trial conducted at 3 neonatal units, 70 premature infants with a gestational age 24 to 29 weeks and birth weight < 1200 g were assigned to 1 of 3 feeding methods: continuous nasogastric feeding, intermittent nasogastric feeding, or intermittent orogastric feeding. Feeding was initiated within 30 hours of birth. Daily enteral and parenteral volumes, caloric and protein intakes, growth, enteral intolerance, and clinical complications were recorded. Cox regression analysis was used to determine primary outcome, the time to achieve full enteral feeding.\n The continuously fed infants achieved full enteral feeding significantly faster than the intermittently fed infants (hazard ratio [HR] = 1.86; 95% confidence interval [CI] = 1.07 to 3.22). In stratified analysis according to birth weight, the improvement was even more pronounced in the smallest infants, those with birth weight < or = 850 g (adjusted HR = 4.13; 95% CI = 1.48 to 11.53). Growth rate was significantly faster in the continuously fed infants ( P = .002).\n In VLBW infants, continuous feeding seems to be better than intermittent feeding with regard to gastrointestinal tolerance and growth." ]	Small sample sizes, methodologic limitations, inconsistencies in controlling variables that may affect outcomes, and conflicting results of the studies to date make it difficult to make universal recommendations regarding the best tube feeding method for premature infants less than 1500 grams. The clinical benefits and risks of continuous versus intermittent nasogastric tube milk feeding cannot be reliably discerned from the limited information available from randomised trials to date.
CD001884	[ "7674464", "8400098", "11698939", "8937605", "8306217", "2405964", "8202769", "7519132", "1903723", "3286039", "3517650", "7572006", "1614196", "1472662", "12514144", "1863725", "2682243", "2521029", "14980901", "1622045", "14595168", "12039820", "19057729", "1382251", "1434725", "2042789", "15734783" ]	[ "Does desmopressin improve hemostasis and reduce blood loss from aortic surgery? A randomized, double-blind study.", "Influence of desmopressin acetate on homologous blood requirements in cardiac surgical patients pretreated with aspirin.", "Desmopressin usage in elective cardiac surgery.", "The role of DDAVP (desmopressin) in orthognathic surgery.", "Use of desmopressin acetate to reduce blood transfusion requirements during cardiac surgery in patients with acetylsalicylic-acid-induced platelet dysfunction.", "Desmopressin acetate in uncomplicated coronary artery bypass surgery: a prospective randomized clinical trial.", "Desmopressin acetate in cardiac surgery: a double-blind, randomized study.", "Randomized study of aprotinin and DDAVP to reduce postoperative bleeding after cardiopulmonary bypass surgery.", "Blood loss and safety with desmopressin or placebo during aorto-iliac graft surgery.", "Does desmopressin acetate reduce blood loss after surgery in patients on cardiopulmonary bypass?", "Treatment with desmopressin acetate to reduce blood loss after cardiac surgery. A double-blind randomized trial.", "Desmopressin acetate does not reduce blood loss during total hip replacement in patients receiving dextran.", "Does desmopressin acetate prophylaxis reduce blood loss after valvular heart operations? A randomized, double-blind study.", "Repeated dose administration of desmopressin acetate in uncomplicated cardiac surgery: a prospective, blinded, randomized study.", "Desmopressin does not decrease blood loss and transfusion requirements in patients undergoing hepatectomy.", "Desmopressin acetate is a mild vasodilator that does not reduce blood loss in uncomplicated cardiac surgical procedures.", "A trial of desmopressin (1-desamino-8-D-arginine vasopressin) to reduce blood loss in uncomplicated cardiac surgery.", "Desmopressin acetate following cardiopulmonary bypass: evaluation of coagulation parameters.", "Prophylactic treatment with desmopressin does not reduce postoperative bleeding after coronary surgery in patients treated with aspirin before surgery.", "Haemostatic responses to desmopressin acetate after primary coronary artery bypass surgery.", "Aprotinin reduces blood loss during spinal surgery in children.", "Mechanical methods of reducing blood transfusion in cardiac surgery: randomised controlled trial.", "Preoperative autologous blood donation reduces the need for allogeneic blood products: a prospective randomized study.", "[Reducing bleeding during extracorporeal circulation interventions by high doses of aprotinin].", "The effect of desmopressin acetate on postoperative hemorrhage in patients receiving aspirin therapy before coronary artery bypass operations.", "Hemodynamic consequences of desmopressin administration after cardiopulmonary bypass.", "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." ]	[ "The purpose of this study was to determine the effect of desmopressin acetate (DDAVP) on blood loss, transfusion requirements, and thromboembolic complications in patients undergoing elective aortic operations.\n A randomized, double-blind trial was carried out during a 3-year period with patients receiving 20 micrograms DDAVP or identical-appearing placebo at the time of aortic cross-clamp placement. In addition to major bleeding and thromboembolic end points, bleeding times and platelet counts were monitored serially.\n Forty-three patients were randomized to receive DDAVP, and 48 were assigned to a placebo. An equivalent proportion of patients with aneurysm and patients with occlusive disease was in each group. In spite of mild prolongation in the postoperative bleeding times and moderate thrombocytopenia, DDAVP had no beneficial effect on blood loss or transfusion requirements. Total blood transfusion amount (mean +/- standard deviation) for patients receiving DDAVP was 3.1 +/- 3.0 U compared with 2.7 +/- 3.0 U for those receiving placebo. For all patients the period associated with the greatest blood loss was the time between heparin administration with cross-clamp application and reversal of heparin with protamine sulfate. The incidence of major thromboembolic complications was similar in both groups.\n Thrombocytopenia and mild platelet dysfunction are common after aortic operation, but DDAVP does not improve hemostasis or lessen transfusion requirements. This study does not rule out a beneficial effect of DDAVP in patients who are undergoing more complex aortic operations or who have major hemostatic aberrations.", "Conflicting results have been reported concerning the effect of the synthetic vasopressin analog desmopressin acetate (DDAVP) on perioperative bleeding and homologous blood requirements in cardiac surgery. Because patients preoperatively treated with platelet-inhibiting drugs are at increased risk of perioperative bleeding, the blood-saving effect of DDAVP was investigated in 40 male patients undergoing primary myocardial revascularization. All patients had taken aspirin within the last 5 days prior to surgery. In a double-blind, randomized trial, the effects of DDAVP (0.3 microgram/kg of body weight) were compared to those of saline placebo on postoperative blood loss and the need to replace blood products. To evaluate the drug's influence on the coagulation and fibrinolytic systems, von Willebrand factor (vWF), the activities of tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI 1), and the split products of cross-linked fibrin (D-dimers) were investigated. The total homologous blood requirement was significantly lower in DDAVP recipients (median 2, range, 0 to 5 U) compared to placebo (median 3.5, range, 0 to 8 U; P < 0.05). Although at all points of measurement (intraoperative and postoperative) transfusion requirement was less in the DDAVP group, hematocrit values of these patients always exceeded those of the placebo group, this difference being significant at the end of the operation. Because no difference in postoperative blood loss was found, the markedly reduced transfusion requirement of the DDAVP-treated patients is explained either by reduced intraoperative bleeding or by a reduced hematocrit of the chest-tube blood.(ABSTRACT TRUNCATED AT 250 WORDS)", "Desmopressin acetate (DDAVP) has been implicated as a promising agent to reduce blood loss in patients undergoing cardiopulmonary bypass.\n The effects of intraoperative desmopressin were studied in 66 patients undergoing coronary artery bypass grafting, randomized equally into desmopressin and control groups. The desmopressin group received 0.3 microg/kg desmopressin at the end of cardiopulmonary bypass.\n Fibrinogen level of both groups significantly reduced at postoperative 2nd hr, whereas a significant rise was observed at postoperative 24th hr with an intergroup difference favoring the control group (p=0.0307). In the desmopressin group, the activation time of factor VIII shortened during the whole postoperative period being significant (p=0.0127) at postoperative 24th hr. Postoperative von Willebrand factor (vWF) levels of the desmopressin group were significantly higher than the preoperative ones. The control group did not show such important changes in factor VIII and vWF measurements. Platelet aggregation times of both groups prolonged at postoperative 2nd hr. The control group showed significant elevation in ADP induced aggregation time at 2nd hr and significant reductions of platelet activation percentage in response to ADP, epinephrine, collagen and ristocetin at 2nd hr. Postoperative blood loss as well as blood transfusion need did not differ between the two groups.\n Despite the improved platelet functions, desmopressin does not seem to have obvious beneficial effects on postoperative hemostasis in patients without any bleeding disorder and undergoing elective cardiac surgery.", "Desmopressin (1-deamino-8-D-argininevasopressin, DDAVP) is a synthetic analog of the antidiuretic hormone L-argininevasopressin. DDAVP has been shown to increase the plasma concentration of endothelial factor VIII, thus increasing coagulant activity. There is evidence from controlled clinical trials indicating that DDAVP can reduce blood loss and transfusion requirements for individuals with normal coagulation profiles undergoing various surgical procedures. This study was conducted to evaluate the efficacy of the DDAVP in reduction of blood loss during orthognathic surgery. Twenty patients, 15 females and 5 males, undergoing bimaxillary osteotomy were randomized into two groups of ten. Perioperatively, group 1 patients received 20 micrograms of DDAVP infused over one-half hour. Group II patients did not receive DDAVP. Hypotensive anesthesia (mean arterial pressure < 60 mm Hg) was routinely employed for both groups. On average, the blood loss in group I patients was 144 ml less per patient than group II patients (p < 0.50). Only 2 of 10 patients in group I lost in excess of 750 ml, while 6 to 10 group II patients experienced blood loss greater than 750 ml (p < 0.20). The average postoperative hematocrit for patients in group I dropped by 6.17 of the preoperative mean hematocrit (p < 0.001). The average drop in hematocrits among the group II patients was 11.61 (p < 0.001). When collated, this hematocrit drop of 11.61 for group II and 6.17 for group I (recipients of DDAVP) proved to be significantly different (p < 0.01). It is concluded from this study that patients receiving a standard dose of DDAVP prior to bimaxillary osteotomy would experience reduced intraoperative blood loss, providing that blood pressure is well controlled and fluid replacement is carefully managed. No significant adverse side effects of desmopressin acetate were observed.", "To determine whether desmopressin acetate (DDAVP) has the ability to reduce blood loss in patients with a known bleeding tendency.\n A randomized, double-blind, placebo controlled study.\n A university teaching hospital.\n Men under the age of 70 years who had taken acetylsalicylic acid within 7 days of scheduled coronary artery bypass surgery. Patients with an abnormal hematologic profile or a history of bleeding or who were receiving heparin or undergoing repeat coronary bypass surgery were excluded. Forty-four patients were randomized with restriction in blocks of 10; 20 received DDAVP and 24 received a placebo.\n Blood loss and blood transfusion requirements.\n Patients treated with DDAVP lost significantly (p < 0.01) less blood than those receiving a placebo (1543 mL versus 2376 mL respectively). Nineteen patients had a blood loss of more than 2000 mL; 15 of these were in the placebo group. Significantly (p < 0.02) fewer patients receiving DDAVP required blood transfusion (9 versus 18).\n DDAVP reduces blood loss during cardiac bypass surgery in patients who have taken acetylsalicylic acid within 7 days before operation.", "Bleeding in coronary artery bypass procedures increases morbidity and exposes patients to the risks associated with blood transfusion. Desmopressin acetate (DDAVP), a synthetic vasopressin analogue, may limit bleeding during cardiac surgery. In a prospective randomized trial, the authors evaluated the ability of DDAVP to reduce perioperative bleeding during uncomplicated coronary bypass operations. Sixty-two patients who underwent coronary artery bypass grafting were randomized to receive intraoperatively either a placebo or DDAVP. Both groups were similar with respect to operative characteristics and preoperative hematologic profiles, von Willebrand factor levels increased postoperatively in both placebo (2.77 +/- 1.06 versus 2.17 +/- 1.51 U) and DDAVP groups (2.75 +/- 0.94 versus 1.80 +/- 0.88 U). Only the increase in the DDAVP groups was significant (p less than 0.001). There was no difference in total blood loss between the placebo (1826 +/- 849 ml) and DDAVP groups (1716 +/- 688 ml). Total red cell transfusions were similar in placebo (3.4 +/- 1.3 units of blood) and DDAVP groups (3.6 +/- 0.8 units). These results do not support the intraoperative use of DDAVP to reduce perioperative bleeding in routine coronary artery bypass surgery.", "Use of desmopressin acetate (DDAVP) for patients having cardiac surgery is controversial. We did a double-blind, randomized study of 83 patients having cardiac operations at Georgetown University Hospital. The effect of DDAVP on bleeding as compared to placebo was evaluated by blood loss, replacement volume, and laboratory tests. There were no significant differences in baseline and intraoperative data between the DDAVP (n = 40) and placebo (n = 43) groups. Total drainage for the first 24 postoperative hours was 1,214 mL (+/- 78) for the DDAVP group and 1,386 mL (+/- 116) for the placebo group (not significant). There were no significant differences in replacement therapy. In this study, administration of DDAVP did not decrease bleeding.", "Patients on cardiopulmonary bypass (CPB) have an increased susceptibility to postoperative bleeding. Previous reports using desmopressin acetate (DDAVP) for the prevention of postoperative bleeding have given contradictory results, whereas the protease inhibitor aprotinin has been shown to reduce blood loss after this type of surgery. This randomized study was performed to assess the efficacy of DDAVP versus aprotinin in the prevention of bleeding after CPB.\n One hundred nine of 122 eligible patients were randomized to four different groups: Group A (n = 28) received aprotinin starting with a bolus of 2 x 10(6) KIU followed by a continuous infusion of 0.5 x 10(6) KIU/h until the end of surgery; group B (n = 25) received of DDAVP 0.3 micrograms/kg i.v. on completion of CPB; group C (n = 28) received two doses of DDAVP, the first as in group B and an additional dose 6 hours after surgery; group D (n = 28) received no treatment. There was a marked reduction of postoperative blood loss either at 12 hours (P < .01) or 72 hours (P < .02) in the aprotinin group compared with all other groups, whereas no significant effect was observed in either of the two DDAVP regimens. A significant reduction in the amount of blood used was observed only in the aprotinin group (P < .01). Of the plasma fibrinolytic components assayed, there was a significant reduction of the fibrin degradation product generation in the aprotinin group (P < .001), whereas a significant systemic hyperfibrinolysis was observed in both DDAVP-treated groups and the control group. No side effects related to the study drugs were observed in any patient.\n Aprotinin inhibited fibrinolysis; this correlated with a significant reduction of postoperative blood loss and need for blood replacement after CPB. Neither one nor two doses of DDAVP had a beneficial effect. Aprotinin offers a better alternative than DDAVP in the prevention of bleeding after CPB.", "In a double blind, placebo controlled study in 50 patients undergoing aorto-iliac graft surgery, we studied the effects of desmopressin given prior to surgery on blood loss and blood transfusion requirements. Desmopressin reduced the number of patients with clinically significant bleeding. Blood loss volumes and transfusion requirements were lower in the desmopressin group, but this could not be verified statistically. Even if our study population has a high incidence of generalised arteriosclerotic disease, there were no clinical manifestations of venous thromboembolism, no increase of graft occlusions and no myocardial infarction during the operative or early postoperative period. Desmopressin may be used in patients with excessive peroperative bleeding or a prolonged preoperative bleeding time. In patients where desmopressin is considered to be haemostatically efficacious, it may be used with a maintained margin of safety.", "It has been suggested that desmopressin acetate (DDAVP) administration reduces blood loss after cardiac surgery. We have investigated the effect of DDAVP administration in a double-blind, randomized, prospective trial including 100 patients placed on cardiopulmonary bypass during surgery. Fifty patients received 0.3 micrograms/kg DDAVP and 50 patients received a placebo administered in a 50 ml saline solution over 15 min when cardiopulmonary bypass had been concluded. Results showed no significant differences either in total blood loss per square meter (458 +/- 206 ml in the DDAVP group vs 536 +/- 304 ml in the placebo group) or in necessity for red cell transfusions (1642 +/- 705 ml in the DDAVP group vs 1574 +/- 645 ml in the placebo group) in the first 72 hr after surgery. Only intraoperative blood loss per square meter was significantly lower (p less than .02) in the DDAVP group (131 +/- 106 ml) as compared with the placebo group (193 +/- 137 ml). The prolongation of bleeding time and the decrease of factor VIII:C and factor VIII:von Willebrand factor 90 min after treatment were significantly lower (p less than .001) in the DDAVP group as compared with the placebo group. We conclude that the administration of DDAVP in patients placed on cardiopulmonary bypass during surgery does not reduce total blood loss and is only effective in reducing intraoperative bleeding.", "Bleeding after cardiopulmonary bypass remains a cause for concern, requiring reexploration of the chest in approximately 3 percent of patients who have had operations on the heart. We examined the possibility that this problem might be alleviated by desmopressin acetate (DDAVP), which increases the plasma level of von Willebrand factor and improves hemostasis in mild hemophilia and other conditions associated with defective platelet function. In a double-blind, prospective, randomized trial, we studied the effect of intraoperative desmopressin acetate in 70 patients undergoing various cardiac operations requiring cardiopulmonary bypass. Patients undergoing uncomplicated primary coronary-artery bypass grafting were not included. The drug significantly reduced mean operative and early postoperative blood loss (1317 +/- 486 ml in the treated group vs. 2210 +/- 1415 ml in the placebo group); of the 14 patients whose 24-hour blood loss exceeded 2000 ml, 11 had received the placebo. Plasma levels of von Willebrand factor were higher after desmopressin acetate than after placebo. Patients with the most bleeding had relatively low levels of von Willebrand factor before operation, suggesting a role for this factor in the hemorrhagic tendency induced by extracorporeal circulation. There were no untoward side effects of desmopressin acetate. We conclude that the administration of desmopressin acetate can be recommended to reduce blood loss in patients undergoing complex cardiac operations. The beneficial effect of the drug on hemostasis after cardiopulmonary bypass may be related to its effect on von Willebrand factor.", "The blood loss-reducing effect of desmopressin during dextran therapy was studied in a double-blind fashion in 79 elderly but otherwise healthy patients with preoperative normal bleeding time undergoing total hip replacement for primary coxarthrosis. An infusion of desmopressin (0.3 microgram/kg body weight) or placebo was randomly administered immediately after administration of spinal anaesthesia and six hours later. Haemostasis was evaluated on the basis of vWF: ristocetin cofactor activity, FVIII: C activity, human tissue plasminogen activator (tPA) plasminogen activator inhibitor type (PAI), beta-thromboglobuline (beta TG) and a clot impedance test (Sonoclot). There were no statistically significant differences (P > 0.05) in mean blood loss or transfusion requirements between the placebo and the desmopressin group. There was a significantly increase (P < 0.01) both in vWF: ristocetin cofactor and in FVIII: C activity after both infusions of desmopressin compared with placebo. There was no significant difference in beta TG, tPA, PAI or Sonoclot analysis between the groups. In conclusion, desmopressin did not reduce blood loss in patients undergoing total hip replacement.", "The effectiveness of prophylactic desmopressin acetate in reducing hemorrhage after cardiopulmonary bypass operations is controversial. We conducted a prospective, randomized, placebo-controlled, double-blind trial to determine its effectiveness and safety in such patients. Eighty-three evaluable patients undergoing valvular heart operations were randomized to receive desmopressin (0.3 microgram/kg) (41) or placebo (42) after cardiac bypass. Demographic characteristics were similar in both groups. There was no significant difference in total 24-hour blood loss between groups (desmopressin 1064.8 +/- 647.1 ml versus placebo 844.4 +/- 507.6 ml; p greater than 0.05), or in the requirement for red blood cell, platelet, or fresh frozen plasma transfusion, or for reexploration for control of hemorrhage. Neither was there a difference in the occurrence of thrombotic complications between groups. Analysis of factor VIII activity, von Willebrand factor, or von Willebrand factor multimers failed to show significant correlations with blood loss or differences between groups except for factor VIII activity, which was significantly higher in the desmopressin group 1 hour after operation than in the placebo group. A detailed comparative analysis of similar trials to determine the reasons for different outcomes suggests that desmopressin should not be used routinely as a prophylactic agent to reduce postsurgical hemorrhage, but that it may be beneficial when used in patients who already manifest excessive bleeding postoperatively.", "The effects of single or repeated doses of desmopressin on blood loss were examined in uncomplicated cardiac surgery, while assessing the potential for thrombogenic side effects. Seventy patients undergoing elective coronary artery bypass grafting (CABG) were studied. Patients were randomized into three blinded groups: Group I received DDAVP (0.3 micrograms/kg), IV, after cardiopulmonary bypass (CPB) and 12 hours later in the Intensive Care Unit (ICU); Group II, DDAVP (0.3 micrograms/kg), IV, after termination of CPB and saline (placebo) 12 hours later in the ICU; Group III, saline (placebo) IV after CPB and 12 hours later in the ICU. Blood loss and bleeding time decreased for Group I at 24 hours (P < 0.04) when compared to Group III; however, blood product replacement, as well as intraoperative and total blood loss at 36 hours, were not different among treatment and control groups. There were four myocardial infarctions recorded in Group I, two in Group II, and one in Group III. These differences were not found to be statistically significant. It is concluded that in routine CABG the prophylactic use of single or repeat dose DDAVP does not effectively decrease blood loss or blood product replacement.", "To determine the effects of desmopressin on coagulation and blood loss in patients undergoing elective partial hepatectomy.\n A randomized, controlled and double-blind study on 59 patients who received either 0.3 micro g x kg(-1) of desmopressin or an equal volume of normal saline (control) infused intravenously over 20 min after induction of general anesthesia.\n There was an increase in plasma levels of factors VIII and von Willebrand after the infusion of study drug in both groups (P < 0.001). The activated partial thromboplastin time was shortened in Group D whereas prothrombin time was prolonged in Group C; (P = 0.02). A large range of intraoperative blood loss (400-7128 mL) was observed, with no significant differences between groups. There were no changes in plasma electrolyte levels or osmolality. Transfusion requirements were similar in both groups.\n Desmopressin did not reduce intraoperative blood loss or transfusion requirements during hepatectomy despite raising clotting factor levels and improving tests of hemostasis.", "Desmopressin acetate (DA) is a synthetic analog of vasopressin that may improve perioperative coagulation in cardiac surgical patients. Twenty-seven adult patients with good left ventricular function and normal preoperative coagulation profiles scheduled to undergo elective cardiac surgery participated in the double-blinded, placebo-controlled study. The 14 patients in the DA group received the drug over 10 minutes (starting 15 minutes after protamine administration). The 13 patients in the placebo group received an equal volume of saline. Preoperative template bleeding time was longer in the placebo group (P = 0.04). Otherwise, there were no statistically significant differences between the groups in demographics, coagulation variables, renal concentrating function, blood loss, or transfusion requirements at any study interval. The only significant hemodynamic differences detected were an increase in cardiac output in the DA group and a corresponding decrease in systemic vascular resistance. Five of 13 patients who received DA required treatment for hypotension, whereas none of 12 patients who received placebo required treatment during the infusion (P = 0.008). The authors conclude that DA causes mild vasodilation, but does not reduce blood loss or transfusion requirements in patients undergoing primary uncomplicated cardiac surgical procedures.", "Previous studies have suggested that desmopressin may reduce the bleeding diathesis that often complicates open-heart surgery. To pursue this question further, we performed a double-blind, randomized, placebo-controlled trial to determine whether the previously reported beneficial effect of desmopressin on hemostasis during complex cardiac surgery was applicable to all elective cardiac surgical procedures involving cardiopulmonary bypass. In 150 consecutive patients, most of whom underwent primary coronary-artery bypass grafting, we compared the effects of intravenous desmopressin (0.3 microgram per kilogram of body weight) with those of saline placebo on postoperative blood loss and the need to replace blood products. The median amount of blood lost within the first 24 hours after operation was similar in the desmopressin and placebo groups (865 vs. 738 ml; P = 0.26). The postoperative use of blood replacement products did not differ significantly between the groups (1025 ml [95 percent confidence interval, 300 to 4140 ml] in the desmopressin group and 860 ml [247 to 5346 ml] in the placebo group). Desmopressin is believed to exert its hemostatic effect by releasing von Willebrand factor. The level of ristocetin cofactor, a functional index of the level of von Willebrand factor, was increased approximately twofold from base line in both treatment groups 90 minutes and 24 hours after the administration of medication. Similarly, the levels of von Willebrand factor multimers increased uniformly in both groups. These findings may be consistent with a normal stress response of von Willebrand factor to major surgery and could explain our failure to detect a therapeutic effect of desmopressin. We conclude that the majority of patients who undergo elective cardiac surgery receive no hemostatic benefit from the use of desmopressin.", "Desmopressin acetate (DDAVP) has been advocated as efficacious in reducing mediastinal bleeding following cardiopulmonary bypass (CPB), and has been shown to ameliorate platelet dysfunction; however, this has not been evaluated during routine coronary artery bypass grafting (CABG). In the present study, this therapy was evaluated utilizing the thromboelastograph (TEG), a rapid, on-line means of diagnosing a coagulopathy. During elective CABG, 20 patients received either DDAVP, 0.3 microgram/kg, intravenously, following heparin reversal after CPB, or a placebo infusion, in a randomized, double-blind fashion. Hemostasis was monitored with both the TEG and conventional coagulation tests. No significant differences between the two groups were found at induction, postprotamine, post-\"study infusion,\" or 2 hours postoperatively, with the exception of the postoperative PTT (31.1 +/- 3.2 v 36.5 +/- 5.9 seconds for DDAVP v placebo, P = 0.03). Total blood products transfused intraoperatively, and in the first 8, 16, 24, or 48 postoperative hours, were also similar between the groups. No manifestations of hypercoagulability were seen, but hypotension during the infusion was noted in four patients receiving DDAVP, and in none of the controls. It is concluded that the expense and potential complications of DDAVP therapy do not justify its routine use in CABG.", "The synthetic vasopressin analog desmopressin has hemostatic properties and may reduce postoperative bleeding after coronary artery bypass grafting (CABG). A study on the effects of recent aspirin ingestion on platelet function in cardiac surgery showed a greater impairment of platelet function in patients treated with aspirin <2 days before the operation. We evaluated the effects of desmopressin on postoperative bleeding in CABG patients who were treated with aspirin 75 or 160 mg until the day before surgery. The study was a prospective, randomized, double-blinded, placebo-controlled, parallel group trial. One-hundred patients were included and divided into two groups. One group received desmopressin 0.3 micro g/kg and the other received placebo (0.9% NaCl) after the neutralization of heparin with protamine sulfate. Postoperative blood loss was recorded for 16 h. The mean (SD) bleeding was 606 (237) mL in the desmopressin group and 601 (301) mL in the placebo group (P = 0.93), representing no significant difference (95% confidence interval, -107 to 117 mL). We conclude that desmopressin does not reduce postoperative bleeding in CABG patients treated with aspirin until the day before surgery.\n Continuation of aspirin until the day before coronary artery bypass grafting may increase postoperative bleeding. The administration of desmopressin to these patients after the neutralization of heparin with protamine sulfate does not reduce postoperative bleeding.", "Previous studies have suggested that the administration of desmopressin (DDAVP) may reduce blood loss after cardiac surgery. The present double-blind, randomized, placebo-controlled trial was performed to determine the effect of DDAVP on haemostasis during and after primary coronary artery bypass surgery. Fifteen patients received an infusion of DDAVP 0.3 microgram/kg and 15 patients received a placebo infusion over 15 min after cardiopulmonary bypass. Following DDAVP administration, the increase in factor VIII:C plasma level was greater than after placebo (the increase at 90 min after treatment 1.10 +/- 0.11 vs. 0.45 +/- 0.09 IU/ml, P less than 0.01). A difference between the treatments tended to occur also in the increase of von Willebrand antigen (0.64 +/- 0.08 vs. 0.23 +/- 0.07 IU/ml, P = 0.0556). A detailed evaluation of various haemostatic parameters showed no significant changes towards hypercoagulability or fibrinolysis. Inspite of the observed potential haemostatic effect of DDAVP, patients treated with DDAVP and placebo had similar postoperative blood losses (950 +/- 185 vs. 1034 +/- 321 ml), similar total haemoglobin losses (45.9 +/- 11.1 vs. 54.7 +/- 25.9 g) and similar red cell transfusion requirements (1.3 (range 0-2) vs. 1.1 (range 0-3) units). The plasma concentrations of factor F VIII:C and von Willebrand factor antigen after cardiopulmonary bypass may explain the failure to achieve a therapeutic effect with DDAVP.", "A prospective blinded, randomized controlled study compared the effect of a perioperative infusion of aprotinin versus placebo during long segment spinal fusions in children.\n To determine whether aprotinin decreases blood loss and transfusion requirements in pediatric patients with spinal deformities undergoing posterior spinal fusions of seven or greater segments.\n Blood loss is a major cause of morbidity during long segment spinal fusion. Several preoperative and intraoperative techniques are currently used to reduce blood loss and transfusion requirements. Aprotinin, an antifibrinolytic and anti-inflammatory agent, has been used to decrease blood loss in cardiac surgical patients. We designed a prospective, randomized, and blinded controlled study to evaluate aprotinin's efficacy in reducing bleeding during pediatric spine surgery.\n After obtaining informed written consent, we studied 44 children and adolescents who were anticipated to be at higher risk for major blood loss during posterior spinal fusion. Children were randomly assigned to receive high dose aprotinin or placebo infusion during the perioperative period. Patients were assessed for blood loss, transfusion requirements, days in the intensive care unit, and days in hospital.\n Demographics in the two groups of patients were similar. The study demonstrated a significant reduction in estimated blood loss (aprotinin 545 cc, placebo 930 cc) and transfusion requirements (aprotinin 1.1 U, placebo 2.2 U). The duration of intensive care unit admission was similar in the two groups, as was the time until discharge.\n This randomized, blinded study suggests that aprotinin significantly decreased blood loss and transfusion requirements in pediatric and adolescent scoliosis surgical patients at increased risk for intraoperative bleeding.", "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.", "We sought to assess the efficacy of preoperative autologous blood donation in reducing patient exposure to allogeneic blood products following elective cardiac surgery.\n We included 48 patients in a prospective study and randomly assigned them into the control or treatment group. We excluded patients with aortic stenosis, main trunk stenosis and unstable angina. Group A (n=23; coronary disease n=21 and valvular disease n=2) was the control group, and group B (n=25; coronary disease n=21, valvular disease n=4) received preoperative autologous blood donation. All patients had cardiopulmonary bypass surgery, and we processed mediastinal blood with a cell-saver device before reinfusion. All patients received aprotinin, and we reinfused blood shed from the mediastinum postoperatively.\n No major peri- or postoperative complications occurred. We interrupted preoperative blood donation in 2 patients (8%) because of worsened angina pectoris. The mean time between the first blood donation and surgery was 22.5 (standard deviation [SD] 9.4, range 12-50) days. In group A, 9 patients (39.1%) were exposed to allogeneic blood products. In group B, 11 patients (47.8%) were exposed to blood products (p=0.73), and 4 (16%) were exposed to allogeneic blood products (p=0.036).\n Preoperative blood donation was completed in 92% of the targeted low-risk population. The procedure significantly reduced exposure to perioperative allogeneic blood products.", "The great risk of severe infectious diseases transmission through blood transfusion, has increased during the last years the effort to reduce the bank blood and its derivates use. Many techniques have proposed to achieve this purpose during and post cardiopulmonary bypass: normovolemic hemodilution, perioperative blood autotransfusion, postoperative return of extra corporeal circuit and chest drains blood and the particular use of some drugs. In the last few years several reports have been presented in the literature concerning the reduction of intra and postoperative bleeding in cardiac surgery by high dose Aprotinin administration. A randomized study with the use of this pharmacologic agent is presented: a group of patients was treated with Aprotinin (shared in two subgroups receiving respectively a different dose of the drug) and a control group. The results were highly encouraging both because of the reduction of peri and postoperative bleeding and because of the bank blood use important reduction.", "It has been suggested that desmopressin acetate has been effective in reducing hemorrhage after coronary artery bypass grafting in patients receiving aspirin before operation. We conducted a prospective, randomized, placebo-controlled, double-blind trial to determine the effectiveness and safety of desmopressin in these patients. Sixty-five patients pretreated with aspirin within 7 days before their scheduled elective coronary artery bypass grafting were randomized to receive desmopressin (0.3 micrograms/kg) or placebo after cessation of bypass and reversal of heparin with protamine. The demographic characteristics and last dose of aspirin were similar in both groups. There was a significant reduction in postoperative blood loss noted between groups for both chest tube blood loss (833 +/- 311 ml for the 1-desamino-8-D-arginine vasopressin [desmopressin] group versus 1176 +/- 674 ml for the placebo group; p = 0.016) and total blood loss (1215 +/- 381 ml for the desmopressin group versus 1637 +/- 761 ml for the placebo group; p = 0.0097). Despite the differences in blood loss between the two groups, the red cell transfusions were not significantly different, but the use of platelets was less in the desmopressin group and almost achieved statistical significance (p = 0.053). Neither was there a difference in the occurrence of thrombotic complications between groups. It appears that desmopressin in this specific subgroup of patients receiving preoperative aspirin is effective as a prophylactic agent for reduction of postsurgical hemorrhage.", "Desmopressin acetate is used to reduce blood loss after cardiac surgery. However, there have been reports that hypotension can occur with infusion of desmopressin and that postoperative blood loss is not reduced. In this randomized, double-blinded study, we investigated the effects of desmopressin on hemodynamics, coagulation, and postoperative blood loss in patients undergoing primary elective coronary artery bypass grafting (CABG). After reversal of heparin effect, 20 patients received desmopressin 0.3 micrograms.kg-1, infused over 15 min, and 20 patients received a placebo. Desmopressin produced a small but significant decrease in diastolic blood pressure when compared with the placebo (50.8 mmHg vs. 57.6 mmHg for the desmopressin- and placebo-treated groups, respectively; P = 0.0372). A 20% or greater decrease in mean arterial pressure was observed in 7 of 20 patients receiving desmopressin, whereas only one patient in the placebo-treated group experienced a decrease of this magnitude (P = 0.0177). Reductions in arterial pressure were secondary to decreases in systemic vascular resistance (SVR) (mean SVR before and after the drug infusion, 1,006 and 766 dyn.s.cm-5, respectively, for the desmopressin-treated group; and 994 and 1,104 dyn.s.cm-5, respectively, for the placebo-treated group; P = 0.0078).(ABSTRACT TRUNCATED AT 250 WORDS)", "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." ]	There is no convincing evidence that desmopressin (DDAVP) minimises peri-operative allogeneic RBC transfusion in patients who do not have congenital bleeding disorders. Although the data suggest that there is some benefit of using DDAVP as a means of reducing peri-operative blood loss the observed reductions were small and generally not clinically important. Based on the currently available evidence, the use of DDAVP to reduce peri-operative blood loss or allogeneic RBC transfusion cannot be supported.

Subsets and Splits

No community queries yet

The top public SQL queries from the community will appear here once available.