Showing papers on "Placebo-controlled study published in 2006"
TL;DR: Natalizumab reduced the risk of the sustained progression of disability and the rate of clinical relapse in patients with relapsing multiple sclerosis and hold promise as an effective treatment for relapsed multiple sclerosis.
Abstract: Background Natalizumab is the first α4 integrin antagonist in a new class of selective adhesion-molecule inhibitors. We report the results of a two-year phase 3 trial of natalizumab in patients with relapsing multiple sclerosis. Methods Of a total of 942 patients, 627 were randomly assigned to receive natalizumab (at a dose of 300 mg) and 315 to receive placebo by intravenous infusion every four weeks for more than two years. The primary end points were the rate of clinical relapse at one year and the rate of sustained progression of disability, as measured by the Expanded Disability Status Scale, at two years. Results Natalizumab reduced the risk of sustained progression of disability by 42 percent over two years (hazard ratio, 0.58; 95 percent confidence interval, 0.43 to 0.77; P<0.001). The cumulative probability of progression (on the basis of Kaplan–Meier analysis) was 17 percent in the natalizumab group and 29 percent in the placebo group. Natalizumab reduced the rate of clinical relapse at one year...
2,940 citations
TL;DR: Current guidelines for universal supplementation with iron and folic acid should be revised because routine supplementation in preschool children in a population with high rates of malaria can result in an increased risk of severe illness and death.
933 citations
TL;DR: In this article, a double blind randomised placebo controlled trial was conducted to determine the efficacy and safety of the anticoagulant fondaparinux in older acute medical inpatients at moderate to high risk of venous thromboembolism.
Abstract: Objective To determine the efficacy and safety of the anticoagulant fondaparinux in older acute medical inpatients at moderate to high risk of venous thromboembolism.
Design Double blind randomised placebo controlled trial.
Setting 35 centres in eight countries.
Participants 849 medical patients aged 60 or more admitted to hospital for congestive heart failure, acute respiratory illness in the presence of chronic lung disease, or acute infectious or inflammatory disease and expected to remain in bed for at least four days.
Interventions 2.5 mg fondaparinux or placebo subcutaneously once daily for six to 14 days.
Outcome measure The primary efficacy outcome was venous thromboembolism detected by routine bilateral venography along with symptomatic venous thromboembolism up to day 15. Secondary outcomes were bleeding and death. Patients were followed up at one month.
Results 425 patients in the fondaparinux group and 414 patients in the placebo group were evaluable for safety analysis (10 were not treated). 644 patients (75.9%) were available for the primary efficacy analysis. Venous thrombembolism was detected in 5.6% (18/321) of patients treated with fondaparinux and 10.5% (34/323) of patients given placebo, a relative risk reduction of 46.7% (95% confidence interval 7.7% to 69.3%). Symptomatic venous thromboembolism occurred in five patients in the placebo group and none in the fondaparinux group (P = 0.029). Major bleeding occurred in one patient (0.2%) in each group. At the end of follow-up, 14 patients in the fondaparinux group (3.3%) and 25 in the placebo group (6.0%) had died.
Conclusion Fondaparinux is effective in the prevention of asymptomatic and symptomatic venous thromboembolic events in older acute medical patients. The frequency of major bleeding was similar for both fondaparinux and placebo treated patients.
807 citations
TL;DR: Adalimumab was well-tolerated during the 24-week study period and was associated with a significant and sustained reduction in the signs and symptoms of active ankylosing spondylitis.
Abstract: Objective
To evaluate the safety and efficacy of adalimumab, a fully human recombinant IgG1 monoclonal antibody that specifically targets human tumor necrosis factor, in patients with active ankylosing spondylitis (AS).
Methods
This was a multicenter, randomized (2:1 ratio), double-blind, placebo-controlled study to evaluate a subcutaneous injection of adalimumab, 40 mg every other week, compared with placebo for 24 weeks. The primary efficacy end point was the percentage of patients with a 20% response according to the ASsessment in Ankylosing Spondylitis International Working Group criteria for improvement (ASAS20) at week 12. Secondary outcome measures included the ASAS20 at week 24 and multiple measures of disease activity, spinal mobility, and function, as well as ASAS partial remission.
Results
At week 12, 58.2% of adalimumab-treated patients (121 of 208) achieved an ASAS20 response, compared with 20.6% of placebo-treated patients (22 of 107) (P < 0.001). More patients in the adalimumab group (45.2% [94 of 208]) than in the placebo group (15.9% [17 of 107]) had at least a 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index at week 12 (P < 0.001). Significant improvements in the ASAS40 response and the response according to the ASAS5/6 criteria at weeks 12 and 24 were also demonstrated (P < 0.001). Partial remission was achieved by more adalimumab-treated patients than placebo-treated patients (22.1% versus 5.6%; P < 0.001). Adalimumab-treated patients reported more adverse events (75.0% versus 59.8% of placebo-treated patients; P < 0.05), but there was no statistically significant difference in the incidence of infections. Most adverse events were mild or moderate in severity.
Conclusion
Adalimumab was well-tolerated during the 24-week study period and was associated with a significant and sustained reduction in the signs and symptoms of active AS.
796 citations
TL;DR: Concomitant supplementation with vitamin C and vitamin E does not prevent pre-eclampsia in women at risk, but does increase the rate of babies born with a low birthweight, and use of these high-dose antioxidants is not justified in pregnancy.
694 citations
TL;DR: It is suggested that treatment of pulmonary fibrosis in SSc with low-dose prednisolone and IV CYC followed by AZA stabilizes lung function in a subset of patients with the disease.
Abstract: OBJECTIVE: The lack of randomized controlled trials (RCTs) in pulmonary fibrosis in systemic sclerosis (SSc) has hampered an evidence-based approach to treatment. This RCT was undertaken to investigate the effects of intravenous (IV) cyclophosphamide (CYC) followed by azathioprine (AZA) treatment in pulmonary fibrosis in SSc. METHODS: Forty-five patients were randomized to receive low-dose prednisolone and 6 infusions (monthly) of CYC followed by oral AZA, or placebo. Primary outcome measures were change in percent predicted forced vital capacity (FVC) and change in single-breath diffusing capacity for carbon monoxide (DLCO). Secondary outcome measures included changes in appearance on high-resolution computed tomography and dyspnea scores. An intent-to-treat statistical analysis was performed. RESULTS: At baseline, there were no significant group differences in factors linked to outcome, including severity of pulmonary fibrosis and autoantibody status. Sixty-two percent of the patients completed the first year of treatment. Withdrawals included 9 patients (6 from the placebo group) with significant decline in lung function, 2 with treatment side effects (both from the active treatment group), and 6 with non-trial-related comorbidity. No hemorrhagic cystitis or bone marrow suppression was observed. Estimation of the relative treatment effect (active treatment versus placebo) adjusted for baseline FVC and treatment center revealed a favorable outcome for FVC of 4.19%; this between-group difference showed a trend toward statistical significance (P = 0.08). No improvements in DLCO or secondary outcome measures were identified. CONCLUSION: This trial did not demonstrate significant improvement in the primary or secondary end points in the active treatment group versus the group receiving placebo. However, for FVC there was a trend toward statistical significance between the 2 groups. This suggests that treatment of pulmonary fibrosis in SSc with low-dose prednisolone and IV CYC followed by AZA stabilizes lung function in a subset of patients with the disease. Therapy was well tolerated with no increase in serious adverse events.
646 citations
TL;DR: For example, donepezil is a cholinesterase inhibitor used to inhibit the breakdown of a chemical neurotransmitter, acetylcholine, by blocking the relevant enzyme as mentioned in this paper.
Abstract: Background
Alzheimer's disease is the most common cause of dementia in older people. One of the aims of therapy is to inhibit the breakdown of a chemical neurotransmitter, acetylcholine, by blocking the relevant enzyme. This can be done by a group of chemicals known as cholinesterase inhibitors.
Objectives
The objective of this review is to assess whether donepezil improves the well-being of patients with dementia due to Alzheimer's disease.
Search methods
The Cochrane Dementia and Cognitive Improvement Group's Specialized Register was searched using the terms 'donepezil', 'E2020' and 'Aricept' on 5 April 2006. This Register contains up-to-date records of all major health care databases and many ongoing trial databases.
Members of the Donepezil Study Group and Eisai Inc were contacted.
Selection criteria
All unconfounded, double-blind, randomized controlled trials in which treatment with donepezil was compared with placebo for patients with mild, moderate or severe dementia due to Alzheimer's disease.
Data collection and analysis
Data were extracted by one reviewer (JSB), pooled where appropriate and possible, and the pooled treatment effects, or the risks and benefits of treatment estimated.
Main results
24 trials are included, involving 5796 participants, of which 15 reported results in sufficient detail for the meta-analyses. Most trials were of 6 months or less duration in selected patients. Patients in 20 trials had mild to moderate disease, in two trials moderate to severe, and in two severe disease. Available outcome data cover domains including cognitive function, activities of daily living, behaviour, global clinical state, adverse events and health care resource costs.
For cognition there is a statistically significant improvement for both 5 and 10 mg/day of donepezil at 24 weeks compared with placebo on the ADAS-Cog scale (-2.01 points MD, 95%CI -2.69 to -1.34, P < 0.00001); -2.80 points, MD 95% CI -3.74 to -2.10, P < 0.00001) and for 10 mg/day donepezil compared with placebo at 24 weeks (5.55 SIB points, 95% CI 3.60 to 7.49, p<0.00001) and 52 weeks (1.84 MMSE points, 95% CI, 0.53 to 3.15, P =0.006).
The results show some improvement in global clinical state (assessed by a clinician) in people treated with 5 and 10 mg/day of donepezil compared with placebo at 24 weeks for the number of patients showing improvement (OR 2.38, 95% CI 1.78 to 3.19, P = < 0.00001, OR 1.82, 95% CI 1.42 to 2.35, P < 0.00001). Benefits of treatment were also seen on measures of activities of daily living and behaviour, but not on the quality of life score. There were significantly more withdrawals before the end of treatment from the 10 mg/day (289/1125 24% 10 mg/day vs 219/1079 20% placebo, OR 1.35, 95% CI 1.11 to 1.65, P = 0.003) but not the 5 mg/day, (100/561 18% 5 mg/day vs 109/568 19% placebo, OR 0.91, 95% CI 0.68 to 1.24, P = 0.56) donepezil group compared with placebo which may have resulted in some overestimation of beneficial changes at 10 mg/day. Benefits on the 10 mg/day dose were marginally larger than on the 5 mg/day dose. The results were similar for all severities of disease.
Two studies presented results for health resource use, and the associated costs. There were no significant differences between treatment and placebo for any item, the cost of any item, and for the total costs, and total costs including the informal carer costs.
Many adverse events were recorded, with more incidents of nausea, vomiting, diarrhoea, muscle cramps, dizziness, fatigue and anorexia (significant risk associated with treatment) in the 10 mg/day group, compared with placebo. There were more incidents of anorexia, diarrhoea, and muscle cramps in the 5 mg/day group compared with placebo, but not of dizziness, fatigue, nausea or vomiting. Very few patients left a trial as a direct result of the intervention.
Authors' conclusions
People with mild, moderate or severe dementia due to Alzheimer's disease treated for periods of 12, 24 or 52 weeks with donepezil experienced benefits in cognitive function, activities of daily living and behaviour. Study clinicians rated global clinical state more positively in treated patients, and measured less decline in measures of global disease severity. There is some evidence that use of donepezil is neither more nor less expensive compared with placebo when assessing total health care resource costs. Benefits on the 10 mg/day dose were marginally larger than on the 5 mg/day dose. Taking into consideration the better tolerability of the 5 mg/day donepezil compared with the 10 mg/day dose, together with the lower cost, the lower dose may be the better option. The debate on whether donepezil is effective continues despite the evidence of efficacy from the clinical studies because the treatment effects are small and are not always apparent in practice.
632 citations
TL;DR: This study has demonstrated that infliximab at a dose of 5 mg/kg is superior to placebo in the treatment of PG and infliximab treatment should be considered in patients with PG.
Abstract: Background: Pyoderma gangrenosum (PG) is a chronic ulcerating skin condition that often occurs in association with inflammatory bowel disease. There have been a number of reports of PG responding to infliximab, a monoclonal antibody against tumour necrosis factor α. Aim: In the first randomised placebo controlled trial of any drug for the treatment of PG, we have studied the role of infliximab in this disorder. Subjects: Patients 18 years of age or older with a clinical diagnosis of PG were invited to take part. Methods: Patients were randomised to receive an infusion of infliximab at 5 mg/kg or placebo at week 0. Patients were then assessed at week 2 and non-responders were offered open labelled infliximab. The primary end point was clinical improvement at week 2, with secondary end points being remission and improvement at week 6. Results: Thirty patients were entered into the study. After randomisation, 13 patients received infliximab and 17 patients received placebo. At week 2, significantly more patients in the infliximab group had improved (46% (6/13)) compared with the placebo group (6% (1/17); p = 0.025). Overall, 29 patients received infliximab with 69% (20/29) demonstrating a beneficial clinical response. Remission rate at week 6 was 21% (6/29). There was no response in 31% (9/29) of patients. Conclusions: This study has demonstrated that infliximab at a dose of 5 mg/kg is superior to placebo in the treatment of PG. Open label treatment with infliximab also produced promising results. Infliximab treatment should be considered in patients with PG.
552 citations
TL;DR: Curcumin seems to be a promising and safe medication for maintaining remission in patients with quiescent UC, and improved both CAI and EI, thus suppressing the morbidity associated with UC.
545 citations
TL;DR: In this paper, the authors examined whether calcium supplementation decreases clinical fracture risk in elderly women and its mechanism of action and concluded that supplementing with calcium carbonate tablets supplying 1200 mg/d is ineffective as a public health intervention in preventing clinical fractures in the ambulatory elderly population owing to poor long-term compliance, but it is effective in those patients who are compliant.
Abstract: Background: Increased dietary calcium intake has been proposed as a population-based public health intervention to prevent osteoporotic fractures. We have examined whether calcium supplementation decreases clinical fracture risk in elderly women and its mechanism of action. Methods: Five-year, double-blind, placebo-controlled study of 1460 women recruited from the population and older than 70 years (mean age, 75 years) who were randomized to receive calcium carbonate, 600 mg twice per day, or identical placebo. The primary end points included clinical incident osteoporotic fractures, vertebral deformity, and adverse events ascertained in 5 years. Bone structure was also measured using dual x-ray absorptiometry of the hip and whole body, quantitative ultrasonography of the heel, and peripheral quantitative computed tomography of the distal radius. Results: Among our patients, 16.1% sustained 1 or more clinical osteoporotic fractures. In the intention-to-treat analysis, calcium supplementation did not significantly reduce fracture risk (hazard ratio, 0.87; 95% confidence interval, 0.67-1.12). However, 830 patients (56.8%) who took 80% or more of their tablets (calcium or placebo) per year had reduced fracture incidence in the calcium compared with the placebo groups (10.2% vs 15.4%; hazard ratio, 0.66; 95% confidence interval, 0.45-0.97). Calciumtreated patients had improved quantitative ultrasonography findings of the heel, femoral neck and whole-body dual x-ray absorptiometry data, and bone strength compared with placebo-treated patients. Of the 92 000 adverse events recorded, constipation was the only event increased by the treatment (calcium group, 13.4%; placebo group, 9.1%). Conclusion: Supplementation with calcium carbonate tablets supplying 1200 mg/d is ineffective as a public health intervention in preventing clinical fractures in the ambulatory elderly population owing to poor long-term compliance, but it is effective in those patients who are compliant. Arch Intern Med. 2006;166:869-875
453 citations
TL;DR: The results support the efficacy of CI therapy for rehabilitating upper extremity motor function in patients with chronic stroke.
Abstract: Background and Purpose— Constraint-Induced Movement therapy (CI therapy) is a neurorehabilitation technique developed to improve use of the more affected upper extremity after stroke. A number of studies have reported positive effects for this intervention, but an experiment with a credible placebo control group has not yet been published. Methods— We conducted a placebo-controlled trial of CI therapy in patients with mild to moderate chronic (mean=4.5 years after stroke) motor deficit after stroke. The CI therapy group received intensive training (shaping) of the more affected upper extremity for 6 hours per day on 10 consecutive weekdays, restraint of the less affected extremity for a target of 90% of waking hours during the 2-week treatment period, and application of a number of other techniques designed to produce transfer to the life situation. The placebo group received a program of physical fitness, cognitive, and relaxation exercises for the same length of time and with the same amount of therapis...
TL;DR: Chloroquine may improve mid-term survival when given in addition to conventional therapy for glioblastoma multiforme (GBM) patients as discussed by the authors, however, the results suggest that larger, more definitive studies of chloroquine as adjuvant therapy for GBM are warranted.
Abstract: Background: Malignant cell clones resistant to chemotherapy and radiotherapy frequently lead to treatment failure in patients with glioblastoma multiforme. Preliminary studies suggest that adding chloroquine to conventional therapy may improve treatment outcomes. Objective: To examine the effect of adding chloroquine to conventional therapy for glioblastoma multiforme. Design: Randomized, double-blind, placebo-controlled trial. Setting: National Institute of Neurology and Neurosurgery of Mexico. Patients: 30 patients with surgically confirmed glioblastoma confined to 1 cerebral hemisphere, with a Karnofsky performance score greater than 70, no comorbid disease, and age younger than 60 years. Interventions: Oral chloroquine at 150 mg/d for 12 months beginning on postoperative day 5 or placebo. All patients received conventional chemotherapy and radiotherapy. Measurements: Primary outcome was survival after surgery; surviving patients were followed up to October 2005. Periodic evaluation using the Karnofsky scale and imaging studies, as well as hematologic tests and ophthalmologic examinations, was done in all patients. Results: Median survival after surgery was 24 months for chloroquine-treated patients and 11 months for controls. At the end of the observation period, 6 patients treated with chloroquine had survived 59, 45, 30, 27, 27, and 20 months, respectively; 3 patients from the control group had survived 32, 25, and 22 months, respectively. Although not statistically significantly different, the rate of death with time was approximately half as large in patients receiving chloroquine as in patients receiving placebo (hazard ratio, 0.52 [95% Cl, 0.21 to 1.26]; P= 0.139). Limitations: The observed advantage of chloroquine may be due to chance; differences in pretreatment characteristics and conventional treatment regimens could not be adjusted for because of the small sample size. Conclusions: Chloroquine may improve mid-term survival when given in addition to conventional therapy for glioblastoma multiforme. These results suggest that larger, more definitive studies of chloroquine as adjuvant therapy for glioblastoma are warranted.
TL;DR: The probiotic strain L johnsonii LA1 (4×109 cfu/day) did not have a sufficient effect, if any, to prevent endoscopic recurrence of Crohn’s disease.
Abstract: BACKGROUND AND AIMS: Early endoscopic recurrence is frequent after intestinal resection for Crohn's disease Bacteria are involved, and probiotics may modulate immune responses to the intestinal flora Here we tested the probiotic strain Lactobacillus johnsonii LA1 in this setting PATIENTS AND METHODS: This was a randomised, double blind, placebo controlled study Patients were eligible if they had undergone surgical resection of 1 in Rutgeerts' classification or an adapted classification for colonic lesions Endoscopic score was the maximal grade of ileal and colonic lesions Analyses were performed primarily on an intent to treat basis RESULTS: Ninety eight patients were enrolled (48 in the LA1 group) At six months, endoscopic recurrence was observed in 30/47 patients (64%) in the placebo group and in 21/43 (49%) in the LA1 group (p = 015) Per protocol analysis confirmed this result Endoscopic score distribution did not differ significantly between the LA1 and placebo groups There were four clinical recurrences in the LA1 group and three in the placebo group CONCLUSION: L johnsonii LA1 (4 x 10(9) cfu/day) did not have a sufficient effect, if any, to prevent endoscopic recurrence of Crohn's disease
TL;DR: Pregabalin 150 to 600 mg/day was effective in relieving central neuropathic pain, improving sleep, anxiety, and overall patient status in patients with spinal cord injury.
Abstract: Siddall et al. conclude with a bullish statement on the effectiveness of pregabalin. The article, acknowledging that all authors worked for or were supported by Pfizer, obfuscates several problems with pregabalin.1
The first problem is study design; all patients were permitted to remain on existing pain therapies except the individuals taking gabapentin, who were required to discontinue treatment at least a week before the study protocol began. This intentionally produced a gabapentin withdrawal state in 34 clients.1 The study may have been biased because those receiving pregabalin were receiving replacement therapy as a byproduct of pre-study drug manipulation; randomization was completed after gabapentin was withdrawn; and the authors did not report which subjects in gabapentin withdrawal were randomized to which treatment group.
The second problem concerns safety. The pregabalin group manifested significantly more adverse side effects, including more serious ones. Twenty-one percent more of the pregabalin-treated patients reported treatment-emergent adverse events compared to placebo. The group discontinuing treatment due to pregabalin was 62% higher than those discontinuing treatment due to placebo.
In addition, side effects included somnolence, dizziness, euphoria (3 with pregabalin vs 0 with placebo), and edema. Adverse …
TL;DR: Abatacept in combination with synthetic DMARDs was well tolerated and improved physical function and physician- and patient-reported disease outcomes, however, abatACEpt in conjunction with biologic background therapies was associated with an increase in the rate of serious adverse events.
Abstract: Objective
To assess the safety of abatacept, a selective costimulation modulator, in patients with active rheumatoid arthritis (RA) who had been receiving ≥1 traditional nonbiologic and/or biologic disease-modifying antirheumatic drugs (DMARDs) approved for the treatment of RA for at least 3 months prior to entry into the study
Methods
This was a 1-year, multicenter, randomized, double-blind, placebo-controlled trial Patients were randomized 2:1 to receive abatacept at a fixed dose approximating 10 mg/kg by weight range, or placebo
Results
The abatacept and placebo groups exhibited similar frequencies of adverse events (90% and 87%, respectively), serious adverse events (13% and 12%, respectively), and discontinuations due to adverse events (5% and 4%, respectively) Five patients (05%) in the abatacept group and 4 patients (08%) in the placebo group died during the study Serious infections were more frequent in the abatacept group than in the placebo group (29% versus 19%) Fewer than 4% of patients in either group experienced a severe or very severe infection The incidence of neoplasms was 35% in both groups When evaluated according to background therapy, serious adverse events occurred more frequently in the subgroup receiving abatacept plus a biologic agent (223%) than in the other subgroups (117–125%)
Conclusion
Abatacept in combination with synthetic DMARDs was well tolerated and improved physical function and physician- and patient-reported disease outcomes However, abatacept in combination with biologic background therapies was associated with an increase in the rate of serious adverse events Therefore, abatacept is not recommended for use in combination with biologic therapy
TL;DR: In an 8-week trial, the low-to-moderate-affinity NMDA antagonist memantine in doses of 5-20 mg/day was not effective in the treatment of major depressive disorder.
Abstract: OBJECTIVE: This study was designed to assess possible antidepressant effects of memantine, a selective N-methyl-D-aspartate (NMDA) receptor antagonist in humans. METHOD: In a double-blind, placebo-controlled study, 32 subjects with major depression were randomly assigned to receive memantine (5–20 mg/day) (N=16) or placebo (N=16) for 8 weeks. Primary efficacy was assessed by performance on the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: The linear mixed models for total MADRS scores showed no treatment effect. CONCLUSIONS: In an 8-week trial, the low-to-moderate-affinity NMDA antagonist memantine in doses of 5–20 mg/day was not effective in the treatment of major depressive disorder.
TL;DR: Donepezil improves cognition and preserves function in individuals with severe Alzheimer's disease who live in nursing homes, by focusing primarily on cognition and activities of daily living.
TL;DR: This formulation of naltrexone was well tolerated and produced a robust, dose-related increase in treatment retention, providing new evidence of the feasibility, efficacy, and tolerability of long-lasting antagonist treatments for opioid dependence.
Abstract: Context Oral naltrexone can completely antagonize the effects produced by opioid agonists. However, poor compliance with naltrexone has been a major obstacle to the effective treatment of opioid dependence. Objective To evaluate the safety and efficacy of a sustained-release depot formulation of naltrexone in treating opioid dependence. Design and Setting Randomized, double-blind, placebo-controlled, 8-week trial conducted at 2 medical centers. Participants Sixty heroin-dependent adults. Interventions Participants were stratified by sex and years of heroin use (≥5 vs Main Outcome Measures Retention in treatment and percentage of opioid-negative urine samples. Results Retention in treatment was dose related, with 39%, 60%, and 68% of patients in the placebo, 192 mg of naltrexone, and 384 mg of naltrexone groups, respectively, remaining in treatment at the end of 2 months. Time to dropout had a significant main effect of dose, with mean time to dropout of 27, 36, and 48 days for the placebo, 192 mg of naltrexone, and 384 mg of naltrexone groups, respectively. The percentage of urine samples negative for opioids, methadone, cocaine, benzodiazepines, and amphetamine varied significantly as a function of dose. When the data were recalculated without the assumption that missing urine samples were positive, a main effect of group was not found for any drugs tested except cocaine, where the percentage of cocaine-negative urine samples was lower in the placebo group. Adverse events were minimal and generally mild. This formulation of naltrexone was well tolerated and produced a robust, dose-related increase in treatment retention. Conclusion These data provide new evidence of the feasibility, efficacy, and tolerability of long-lasting antagonist treatments for opioid dependence.
TL;DR: The risk of serious infections in patients receiving the approved infliximab dose of 3 mg/kg plus MTX was similar to that in patients received MTX alone, and patients receiving an unapproved induction regimen followed by a 10mg/kg maintenance regimen had an increased risk ofserious infections through week 22.
Abstract: Objective
To assess the risk of serious infections following 22 weeks of infliximab therapy, and to further characterize the safety profile of infliximab in combination with background treatments during 1 year in patients with rheumatoid arthritis (RA) with various comorbidities.
Methods
Patients with active RA despite receiving methotrexate (MTX) were randomly assigned to receive infusions of placebo (group 1, n = 363), 3 mg/kg infliximab (group 2, n = 360), or 10 mg/kg infliximab (group 3, n = 361) at weeks 0, 2, 6, and 14. At week 22, patients in placebo group 1 began receiving 3 mg/kg infliximab, and patients in group 3 continued to receive an infliximab dose of 10 mg/kg. Patients in group 2 who failed to meet predefined response criteria received increasing doses of infliximab in increments of 1.5 mg/kg.
Results
At week 22, the relative risk of developing serious infections in groups 2 and 3, compared with group 1, was 1.0 (95% confidence interval [95% CI] 0.3–3.1, P = 0.995) and 3.1 (95% CI 1.2–7.9, P = 0.013), respectively. The incidence of serious adverse events was 7.8% in groups 2 and 3 compared with 7.5% in group 1. From week 22 to week 54, 11.8%, 9.9%, and 10.3% of patients in groups 1, 2, and 3, respectively, reported occurrences of serious adverse events. Through week 54, 1 patient in group 1, 2 patients in group 2, and 4 patients in group 3 developed active tuberculosis.
Conclusion
The risk of serious infections in patients receiving the approved infliximab dose of 3 mg/kg plus MTX was similar to that in patients receiving MTX alone. Patients receiving the unapproved induction regimen of 10 mg/kg infliximab plus MTX followed by a 10 mg/kg maintenance regimen had an increased risk of serious infections through week 22.
TL;DR: Adjunctive ethyl-EPA is an effective and well-tolerated intervention in bipolar depression and significantly improved the HRSD and CGI scores.
Abstract: Background Epidemiological and clinical studies suggest that increased intake of eicosapentaenoic acid (EPA) alleviates unipolar depression.
Aims To examine the efficacy of EPA in treating depression in bipolar disorder.
Method In a12-week, double-blind study individuals with bipolar depression were randomly assigned to adjunctive treatment with placebo ( n =26) or with 1 g/day ( n =24) or 2 g/day ( n =25) of ethyl-EPA. Primary efficacy was assessed by the Hamilton Rating Scale for Depression (HRSD), with changes in the Young Mania Rating Scale and Clinical Global Impression Scale (CGI) as secondary outcome measures.
Results There was no apparent benefit of 2 g over 1 g ethyl-EPA daily. Significant improvement was noted with ethyl-EPA treatment compared with placebo in the HRSD ( P =0.04) and the CGI ( P =0.004) scores. Both doses were well tolerated.
Conclusions Adjunctive ethyl-EPA is an effective and well-tolerated intervention in bipolar depression.
TL;DR: The antiinflammatory effect of macrolide antibiotics has been well‐established, as has their role in the treatment of certain disorders of chronic airway inflammation, but this effect has not been tested in a randomized, placebo‐controlled study.
Abstract: Objectives: The antiinflammatory effect of macrolide antibiotics has been well-established, as has their role in the treatment of certain disorders of chronic airway inflammation. Several studies have suggested that long-term, low-dose macrolides may be efficacious in the treatment of chronic rhinosinusitis; however, these studies have lacked a control group. To date, this effect has not been tested in a randomized, placebo-controlled study. Method: The authors conducted a double-blind, randomized, placebo-controlled clinical trial on 64 patients with chronic rhinosinusitis. Subjects received either 150 mg roxithromycin daily for 3 months or placebo. Outcome measures included the Sinonasal Outcome Test-20 (SNOT-20), measurements of peak nasal inspiratory flow, saccharine transit time, olfactory function, nasal endoscopic scoring, and nasal lavage assays for interleukin-8, fucose, and a2-macroglobulin. Results. There were statistically significant improvements in SNOT-20 score, nasal endoscopy, saccharine transit time, and IL-8 levels in lavage fluid (P < .05) in the macrolide group. A correlation was noted between improved outcome measures and low IgE levels. No significant improvements were noted for olfactory function, peak nasal inspiratory flow, or lavage levels for fucose and a2-macroglobulin. No improvement in any outcome was noted in the placebo-treated patients. Conclusion: These findings suggest that macrolides may have a beneficial role in the treatment of chronic rhinosinusitis, particularly in patients with low levels of IgE, and supports the in vitro evidence of their antiinflammatory activity. Additional studies are required to assess their place in clinical practice.
TL;DR: The results support the prescription of agomelatine 25 mg as the usual therapeutic dose, and suggest that increasing the dose to 50 mg may be beneficial for some patients without reducing tolerability.
TL;DR: Eerrlotinib not only improves survival in previously treated patients with NSCLC, but also improves tumor-related symptoms and important aspects of QOL.
Abstract: Purpose This report describes the quality of life (QOL) findings of a randomized placebo controlled study of erlotinib, an epidermal growth factor receptor inhibitor, in patients with non‐small-cell lung cancer (NSCLC). Patients and Methods This double-blind phase III trial randomly assigned 731 patients with NSCLC who had progressed after prior chemotherapy to erlotinib 150 mg daily or placebo, with survival as the primary study outcome. QOL was assessed by European Organisation for Research and Treatment of Cancer QLQ-C30 and the lung cancer module QLQ-LC13. The primary end points for QOL analysis were time to deterioration of three common lung cancer symptoms: cough, dyspnea, and pain. Results Survival was significantly longer (hazard ratio, 0.70; P .0001) in the erlotinib arm. Compliance with QOL was 87% at baseline and more than 70% during treatment. Patients receiving erlotinib had significantly longer median time to deterioration for all three symptoms (4.9 v 3.7 months for cough [P .04]; 4.7 v 2.9 months for dyspnea [P .04], and 2.8 v 1.9 months for pain [P .03]). QOL response analyses showed that 44%, 34%, and 42% of patients receiving erlotinib had improvement in these three symptoms, respectively. This was accompanied by a significant improvement in the physical function (31% erlotinib v 19% placebo, P .01), and global QOL (35% v 26%, P .0001). Patients with complete or partial response were more likely to have improvement in the QOL response than patients with stable or progressive disease (P .01).
TL;DR: Compared to placebo, olanzapine delays relapse into subsequent mood episodes in bipolar I disorder patients who responded to open-label acute treatment with olanZapine for a manic or mixed episode.
Abstract: OBJECTIVE: In a placebo-controlled, double-blind study, the authors investigated the efficacy and safety of olanzapine as monotherapy in relapse prevention in bipolar I disorder. METHOD: Patients achieving symptomatic remission from a manic or mixed episode of bipolar I disorder (Young Mania Rating Scale [YMRS] total score ≤12 and 21-item Hamilton Depression Rating Scale [HAM-D] score ≤8) at two consecutive weekly visits following 6–12 weeks of open-label acute treatment with 5–20 mg/day of olanzapine were randomly assigned to double-blind maintenance treatment with olanzapine (N=225) or placebo (N=136) for up to 48 weeks. The primary measure of efficacy was time to symptomatic relapse into any mood episode (YMRS score ≥15, HAM-D score ≥15, or hospitalization). RESULTS: Time to symptomatic relapse into any mood episode was significantly longer among patients receiving olanzapine (a median of 174 days, compared with a median of 22 days in patients receiving placebo). Times to symptomatic relapse into manic...
TL;DR: Long term use of low dose azithromycin in young patients with cystic fibrosis has a beneficial effect on lung disease expression, even before infection with Pseudomonas aeruginosa.
Abstract: Background: Macrolides display immunomodulatory effects that may be beneficial in chronic inflammatory pulmonary diseases. The aim of the study was to document whether long term use of azithromycin may be associated with respiratory benefits in young patients with cystic fibrosis. Methods: A multicentre, randomised, double blind, placebo controlled trial was conducted from October 2001 to June 2003. The criteria for enrolment were age older than 6 years and forced expiratory volume in 1 second (FEV 1 ) of 40% or more. The active group received either 250 mg or 500 mg (body weight 1 . Results: Eighty two patients of mean (SD) age 11.0 (3.3) years and mean (SD) FEV 1 85 (22)% predicted were randomised: 40 in the azithromycin group and 42 in the placebo group. Nineteen patients were infected with Pseudomonas aeruginosa . The relative change in FEV 1 at month 12 did not differ significantly between the two groups. The number of pulmonary exacerbations (count ratio 0.50 (95% CI 0.32 to 0.79), p Conclusion: Long term use of low dose azithromycin in young patients with cystic fibrosis has a beneficial effect on lung disease expression, even before infection with Pseudomonas aeruginosa .
TL;DR: The general use ofprednisone in HSP is not supported, but patients with disturbing symptoms may benefit from early treatment, because prednisone reduces extrarenal symptoms and is effective in altering (but not preventing) the course of renal involvement.
TL;DR: The results indicate no statistically significant benefit from single agent EPA in the treatment of cancer cachexia and future studies should concentrate on other agents or combination regimens.
Abstract: Purpose Eicosapentaenoic acid (EPA) has been proposed to have specific anticachectic effects. This trial compared EPA diethyl ester with placebo in cachectic cancer patients for effects on weight and lean body mass. Patients and Methods Five hundred eighteen weight-losing patients with advanced gastrointestinal or lung cancer were studied in a multicenter, double-blind, placebo controlled trial. Patients were randomly assigned to receive a novel preparation of pure EPA at a dose o f2go r 4g daily or placebo (2g EPA, n 175; 4 g EPA, n 172; placebo, n 171). Patients were assessed at 4 weeks and 8 weeks. Results The groups were well balanced at baseline. Mean weight loss at baseline was 18% (n 518). Over the 8-week treatment period, both intention-to-treat analysis and per protocol analysis revealed no statistically significant improvements in survival, weight, or other nutritional variables. There was, however, a trend in favor of EPA with analysis of the primary end point, weight, at 8 weeks showing a borderline, nonsignificant treatment effect (P .066). Relative to placebo, mean weight increased by 1.2 kg with 2 g EPA (95% CI, 0 kg to 2.3 kg) and by 0.3 kg with 4g EPA (0.9 kg to 1.5 kg). Conclusion The results indicate no statistically significant benefit from single agent EPA in the treatment of cancer cachexia. Future studies should concentrate on other agents or combination regimens.
TL;DR: Transdermal testosterone therapy via a skin patch improved sexual desire and other sexual function domains and was well tolerated in these oophorectomized women with HSDD receiving concomitant transdermal estrogen.
Abstract: Background: Oophorectomy reduces serum testosterone levels. We studied the efficacy and safety of transdermal testosterone in treating hypoactive sexual desire disorder in surgically menopausal women. Methods: A 24-week, randomized, double-blind, placebo-controlled,parallel-group,multicentertrialwasconducted in women (aged 24-70 years) who developed distressful low sexual desire after bilateral salpingooophorectomy and hysterectomy and who were receiving oral estrogen therapy. Women were randomized to receive placebo (n=119) or testosterone patches in dosagesof150µg/d(n=107),300µg/d(n=110),or450µg/d (n=111) twice weekly for 24 weeks. Sexual desire and frequency of satisfying sexual activity were primary efficacy outcome measures. Results:Ofthe447womenrandomized,318(71%)completed the trial. Compared with placebo, women receiving the 300-µg/d testosterone patch had significantly greater increases from baseline in sexual desire (67% vs 48%; P=.05) and in frequency of satisfying sexual activity (79% vs 43%; P=.049). The 150-µg/d group showed no evidence of a treatment effect. The 450-µg/d group also was not statistically different from the 300-µg/d or placebo groups. Marginally significant linear doseresponse trends were observed for total satisfying sexual activity and sexual desire at 24 weeks (P=.06 and .06, respectively). Adverse events occurred with similar frequency in both groups; no serious safety concerns were observed.
TL;DR: Methylphenidate was not significantly superior to placebo after 1 week of treatment, and the role of daily telephone calls from a research nurse should be explored as a palliative care intervention.
Abstract: Purpose To evaluate the effectiveness of patient-controlled methylphenidate as compared with placebo in cancer patients with fatigue, as measured by the Functional Assessment for Chronic Illness Therapy-Fatigue (FACIT-F). Patients and Methods Patients with a fatigue score of at least 4 on a scale of 0 to 10 (0 = no fatigue, 10 = worst possible fatigue) and hemoglobin level of at least 10 g/dL were included. Patients were randomly assigned to receive 5 mg methylphenidate or placebo every 2 hours as needed (maximum of four capsules a day), for 7 days. Patients completed a daily diary including study drug record and fatigue intensity. A research nurse telephoned patients daily to assess toxicity and fatigue level. All patients were offered open-label methylphenidate for 4 weeks. FACIT-F and the Edmonton Symptom Assessment System (ESAS) were assessed at baseline, and days 8, 15, and 36. The FACIT-F fatigue subscore on day 8 was considered the primary end point. Results Of 112 patients randomly assigned, 52 pa...
TL;DR: Metformin therapy is safe and effective in abrogating weight gain, decreased insulin sensitivity, and abnormal glucose metabolism resulting from treatment of children and adolescents with atypical antipsychotics.
Abstract: Objective: Second-generation, or atypical, antipsychotics effectively treat psychiatric illness in children and adolescents. However, weight gain and abnormalities in insulin sensitivity, including diabetes, complicate this therapy. Method: A 16-week double-blind, placebo-controlled trial was conducted to evaluate the effectiveness of metformin in managing weight gain in 39 subjects, ages 10–17, whose weight had increased by more than 10% during less than 1 year of olanzapine, risperidone, or quetiapine therapy. Body weight, body mass index (kilograms per square meter of height), and waist circumference were measured regularly, as were fasting insulin and glucose levels. Results: Weight was stabilized in subjects receiving metformin, while those receiving placebo continued to gain weight (0.31 kg/week). Because the study was conducted with growing children, metformin treatment resulted in reduction in z scores for both weight and body mass index. The homeostasis model assessment, a surrogate indicator of ...