A meta-analysis of the placebo response in complementary and alternative medicine trials of irritable bowel syndrome.

Among patients with irritable bowel syndrome (IBS) enrolled in clinical trials of conventional medical therapy, the placebo response rate is high. IBS patients also frequently use complementary and alternative medicine (CAM), which may act through an 'enhanced placebo effect'. The purpose of this study was to estimate the magnitude of the placebo response rate in CAM trials for IBS and to identify factors that influence this response. We performed a systematic review and meta-analysis of randomized, placebo-controlled clinical trials of CAM therapies for IBS identified from MEDLINE/EMBASE/PsychLIT databases from 1970 to 2006. Placebo and active treatment response rates for global symptom improvement were assessed. Nineteen studies met the inclusion criteria. The pooled estimate of the placebo response rate was 42.6% (95% confidence interval, 38.0-46.5%). Significant heterogeneity existed across trials (range 15.0-72.2%, P < 0.00001). Higher placebo response rates correlated with a longer duration of treatment (r = 0.455, P = 0.05) and a greater number of office visits (r = 0.633, P = 0.03). Among IBS patients in CAM trials, the placebo response rate is high. That this rate is similar in magnitude to that seen in conventional medicine trials suggests that the placebo response is independent of the type of therapy used and that it is not particularly 'enhanced' in CAM trials.

Safety of nifedipine in angina pectoris: a meta-analysis.

-Our objective was to compare cardiovascular event rates in patients with stable angina receiving nifedipine as monotherapy or combination therapy and in active drug controls. A MEDLARS search of published articles from 1966 to 1995 in English, French, German, Italian, or Spanish, supplemented by a manual search of bibliographies, identified 60 randomized controlled trials that met protocol criteria. Blinded articles were extracted by 2 physicians. The pooled risks of death, withdrawal, and cardiovascular event were computed and expressed as odds ratios (ORs) for all nifedipine formulations and relative to same study control drug regimens. Thirty cardiovascular events were reported in 2635 nifedipine exposures (1.14%) and 19 events in 2655 other active drug exposures (0.72%). Unadjusted ORs for nifedipine versus controls were 1.40 (95% CI, 0.56 to 3.49) for major events (death, nonfatal myocardial infarction, stroke, revascularization procedure), 1.75 (95% CI, 0.83 to 3.67) for increased angina, and 1.61 (95% CI, 0.91 to 2.87) for all events (major events plus increased angina). Episodes of increased angina were more frequent on immediate-release nifedipine (OR, 4.19 [95% CI, 1.41 to 12.49]) and on nifedipine monotherapy (OR, 2.61 [95% CI, 1.30 to 5.26]). The OR for immediate-release nifedipine was significantly higher than that for sustained-release/extended-release nifedipine (P=0.001), and the OR for nifedipine monotherapy was higher than that for nifedipine combination therapy (P=0.03). Increased risks of cardiovascular events in patients with stable angina on nifedipine were due primarily to more episodes of increased angina, confined to the immediate-release formulation and to nifedipine monotherapy.

Safety of nifedipine in patients with hypertension: a meta-analysis.

Our objective was to compare cardiovascular event rates in patients with mild or moderate hypertension who received nifedipine with active drug controls. We performed a MEDLARS search using the MeSH heading "hypertension" and the text word "nifedipine" to identify all articles that were published between 1966 and August 1995 in English, French, German, Italian, and Spanish languages and that involved human subjects. The computerized search was supplemented by a manual search of article bibliographies. Review of 1880 citations revealed 98 randomized controlled clinical trials that met protocol criteria. Articles were extracted independently by two doctors who were blinded for author, institution, and treatment regimen, using a structured, pretested extraction form. Differences of opinion were resolved by consensus. Fourteen events occurred in 5198 exposures (0.27%) to nifedipine and 24 events in 5402 exposures (0.44%) to other active drug controls. Unadjusted odds ratios for nifedipine versus controls were 0.49 (95% confidence interval [CI], 0.22-1.09) for definitive events (death, nonfatal myocardial infarction or stroke, revascularization procedure) and 0.61 (95% CI, 0.31-1.17) for all events (definitive plus increased angina). The odds ratio for nifedipine monotherapy (sustained- or extended-release in 91% of exposures) was nonsignificantly higher for definitive and all events (odds ratio, 1.40; 95% CI, 0.49-4.03 and odds ratio, 1.39; 95% CI, 0.59-3.32, respectively). The odds ratio for nifedipine in combination with another drug was significantly lower for definitive and all events (odds ratio, 0.09; 95% CI, 0.01-0.66 and odds ratio, 0.15; 95% CI, 0.03-0.65, respectively). Differences in odds ratio for nifedipine monotherapy and combined therapy were statistically significant (P=.02 for definitive events and P=.001 for all events). Results support the safety of sustained- and extended-release nifedipine in the treatment of mild or moderate hypertension when it is used in combination with other drugs.

Searching for signals: mortality and cardiovascular events in published randomized control trials of nifedipine in ischemic heart disease and hypertension.

UNLABELLED: META-ANALYSIS: A meta-analysis of published randomized control trials of nifedipine in hypertension and stable angina pectoris was performed. RESULTS: The results suggest a formulation-dependent increased risk of mortality and adverse cardiovascular outcomes for monotherapy use in patients with stable angina pectoris. No increased risk was seen in the hypertension studies.

Functional electrostimulation in poststroke rehabilitation: a meta-analysis of the randomized controlled trials.

OBJECTIVE: To assess the efficacy of functional electrical stimulation (FES) in the rehabilitation of hemiparesis in stroke. DESIGN: A meta-analysis combined the reported randomized controlled trials of FES in stroke, using the effect size method of Glass, and the DerSimonian-Laird Random Effects Method for pooling studies. SETTING: The included studies were published between 1978 and 1992. They were conducted in academic rehabilitation medicine settings. PATIENTS: In all included studies, patients were in poststroke rehabilitation. The mean time after stroke varied from 1.5 to 29.2 months. INTERVENTION: FES applied to a muscle or associated nerve in a hemiparetic extremity was compared to No FES. MAIN OUTCOME MEASURE: Change in paretic muscle force of contraction following FES was compared to change without FES. RESULTS: For the four included studies, the mean effect size was .63 (95% CI: .29, .98). This result was statistically significant (p < .05). CONCLUSION: Pooling from randomized trials supports FES as promoting recovery of muscle strength after stroke. This effect is statistically significant. There is a reasonable likelihood of clinical significance as well.

Biofeedback therapy in poststroke rehabilitation: a meta-analysis of the randomized controlled trials.

OBJECTIVE: To assess the efficacy of biofeedback therapy in poststroke rehabilitation. DESIGN: A meta-analysis of the reported randomized control trials of biofeedback therapy in poststroke rehabilitation was performed. Data were analyzed using the effect size method and pooled using the Der Simonian-Laird Random Effects Model. Study quality was assessed according to the method of Chalmers. SETTING: All included studies were conducted in academically based rehabilitation settings. PATIENTS: Patients were in the rehabilitative phase of their illness. The timing of the intervention from the acute event did vary greatly between and within studies. INTERVENTION: Biofeedback therapy was applied to a paretic limb of patients in the study group. Both treatment and control groups received standard physical therapy. MAIN OUTCOME MEASURE: Change in range of motion of a joint of a paretic limb as a result of treatment was examined. This measure was chosen after the eligible studies were evaluated for combinable end points. RESULTS: A total of eight studies were included in the analysis. The mean effect size for change in lower extremity range of motion as a result of biofeedback therapy was 1.50 (95% confidence interval [CI]: -0.59, 3.59). For the upper extremity the effect size was 2.30 (95% CI: -1.06, 5.66). Both results were not significant at the p < .05 level. Statistical tests showed significant heterogeneity among studies, validating the use of the Random Effects Model. CONCLUSION: Results of pooling available randomized control trials do not support the efficacy of biofeedback in restoring the range of motion of hemiparetic joints. Nevertheless, because the calculated mean effect sizes were large, with associated wide confidence intervals, the possibility of a type II error masking an important clinical benefit needs to be considered in evaluating this result.