Jonathan Ac Sterne

Are the clinical effects of homoeopathy placebo effects? Comparative study of placebo-controlled trials of homoeopathy and allopathy.

BACKGROUNDnHomoeopathy is widely used, but specific effects of homoeopathic remedies seem implausible. Bias in the conduct and reporting of trials is a possible explanation for positive findings of trials of both homoeopathy and conventional medicine. We analysed trials of homoeopathy and conventional medicine and estimated treatment effects in trials least likely to be affected by bias.nnnMETHODSnPlacebo-controlled trials of homoeopathy were identified by a comprehensive literature search, which covered 19 electronic databases, reference lists of relevant papers, and contacts with experts. Trials in conventional medicine matched to homoeopathy trials for disorder and type of outcome were randomly selected from the Cochrane Controlled Trials Register (issue 1, 2003). Data were extracted in duplicate and outcomes coded so that odds ratios below 1 indicated benefit. Trials described as double-blind, with adequate randomisation, were assumed to be of higher methodological quality. Bias effects were examined in funnel plots and meta-regression models.nnnFINDINGSn110 homoeopathy trials and 110 matched conventional-medicine trials were analysed. The median study size was 65 participants (range ten to 1573). 21 homoeopathy trials (19%) and nine (8%) conventional-medicine trials were of higher quality. In both groups, smaller trials and those of lower quality showed more beneficial treatment effects than larger and higher-quality trials. When the analysis was restricted to large trials of higher quality, the odds ratio was 0.88 (95% CI 0.65-1.19) for homoeopathy (eight trials) and 0.58 (0.39-0.85) for conventional medicine (six trials).nnnINTERPRETATIONnBiases are present in placebo-controlled trials of both homoeopathy and conventional medicine. When account was taken for these biases in the analysis, there was weak evidence for a specific effect of homoeopathic remedies, but strong evidence for specific effects of conventional interventions. This finding is compatible with the notion that the clinical effects of homoeopathy are placebo effects.

ArticlesIndications for red blood cell transfusion in cardiac surgery: a systematic review and meta-analysis

BACKGROUNDnGood blood management is an important determinant of outcome in cardiac surgery. Guidelines recommend restrictive red blood cell transfusion. Our objective was to systematically review the evidence from randomised controlled trials and observational studies that are used to inform transfusion decisions in adult cardiac surgery.nnnMETHODSnWe did a systematic review by searching PubMed, Embase, Cochrane Library, and DARE, from inception to May 1, 2015, databases from specialist societies, and bibliographies of included studies and recent relevant review articles. We included randomised controlled trials that assessed the effect of liberal versus restrictive red blood cell transfusion in patients undergoing cardiac and non-cardiac surgery, and observational studies that assessed the effect of red blood cell transfusion compared with no transfusion on outcomes in adult cardiac patients after surgery. We pooled adjusted odds ratios using fixed-effects and random-effects meta-analyses. The primary outcome was 30-day mortality.nnnFINDINGSnWe included data from six cardiac surgical randomised controlled trials (3352 patients), 19 non-cardiac surgical trials (8361 patients), and 39 observational studies (232,806 patients). The pooled fixed effects mortality odds ratios comparing liberal versus restrictive transfusion thresholds was 0.70 (95% CI 0.49-1.02; p=0.060) for cardiac surgical trials and 1.10 (95% CI 0.96-1.27; p=0.16) for trials in settings other than cardiac surgery. By contrast, observational cohort studies in cardiac surgery showed that red blood cell transfusion compared with no transfusion was associated with substantially higher mortality (random effects odds ratio 2.72, 95% CI 2.11-3.49; p<0.0001) and other morbidity, although with substantial heterogeneity and small study effects.nnnINTERPRETATIONnEvidence from randomised controlled trials in cardiac surgery refutes findings from observational studies that liberal thresholds for red blood cell transfusion are associated with a substantially increased risk of mortality and morbidity. Observational studies and trials in non-cardiac surgery should not be used to inform treatment decisions or guidelines for patients having cardiac surgery.nnnFUNDINGnNone.