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Abstract: Objective: To determine the validity of transcutaneous oximetry (TcPO2) as a predictor of lower limb amputation healing complications. Design: A systematic review and meta-analysis. Methods: We searched five major medical databases, relevant review articles and reference lists and included all studies that evaluated TcPO2 for its ability to predict lower limb amputation healing failure. We selected eligible articles and conducted data abstraction independently and in duplicate. Results: Thirty-one studies, enrolling 1824 patients with 1960 amputations, met our inclusion criteria. Only one study reported undertaking a multivariable analysis, which demonstrated that a TcPO2 level below 20 mmHg was an independent predictor of re-amputation occurrence (adjusted odds ratio (OR) 3.08, 95% confidence interval (CI) 1.19–7.98). Fourteen prospective cohort studies reported data that allowed for the calculation of an unadjusted relative risk of lower limb amputation healing complications leading to amputation revision associated with a TcPO2 level below cut-offs of 10 mmHg (1.80; 95% CI 1.19–2.72), 20 mmHg (1.75; 95% CI 1.27–2.40) 30 mmHg (1.41; 95% CI 1.22–1.62) and 40 mmHg (1.24; 95% CI 1.13–1.39). Conclusions: This review suggests that TcPO2 predicts healing complications of lower limb amputations. A value of less than 40 mmHg results in a 24% increased risk of healing complication compared to over 40 mmHg and the risk further increases as the TcPO2 decreases. There is, however, insufficient evidence to judge whether this tool adds important information beyond clinical data or to suggest an optimal threshold value. There is a need for a large, sufficiently powered study that adjusts for appropriate clinical variables. [Copyright &y& Elsevier]

Background The role of nitrous oxide in modern anaesthetic practice is contentious. One concern is that exposure to nitrous oxide may increase the risk of cardiovascular complications. ENIGMA II is a large randomized clinical trial currently underway which is investigating nitrous oxide and cardiovascular complications. Before the completion of this trial, we performed a systematic review and meta-analysis, using Cochrane methodology, on the outcomes that make up the composite primary outcome. Methods We used conventional meta-analysis and trial sequential analysis (TSA). We reviewed 8282 abstracts and selected 138 that fulfilled our criteria for study type, population, and intervention. We attempted to contact the authors of all the selected publications to check for unpublished outcome data. Results Thirteen trials had outcome data eligible for our outcomes. We assessed three of these trials as having a low risk of bias. Using conventional meta-analysis, the relative risk of short-term mortality in the nitrous oxide group was 1.38 [95% confidence interval (CI) 0.22–8.71] and the relative risk of long-term mortality in the nitrous oxide group was 0.94 (95% CI 0.80–1.10). In both cases, TSA demonstrated that the data were far too sparse to make any conclusions. There were insufficient data to perform meta-analysis for stroke, myocardial infarct, pulmonary embolus, or cardiac arrest. Conclusion This systematic review demonstrated that we currently do not have robust evidence for how nitrous oxide used as part of general anaesthesia affects mortality and cardiovascular complications. [ABSTRACT FROM AUTHOR]

There have been over 100 randomized clinical trials ( RCTs) of diverse regimens of antiretroviral therapy for treatment-naïve human immunodeficiency virus-positive patients. A further 400 systematic reviews and meta-analyses are informed by these trials. There are, however, difficulties in using systematic reviews and meta-analyses of this clinical evidence to inform guidelines and clinical practice. Several issues can make the interpretation of comparative effectiveness challenging. In this article, we review the key challenges in interpreting multiple trials in this population. We specifically examine the network geometry of the clinical trial comparisons, the predominance of non-inferiority trial designs, issues related to potential class effects, heterogeneous documentation of adverse events, and a relative lack of RCTs that reflect specific current clinical guideline recommendations. We conclude with recommendations for future clinical trials and meta-analyses. [ABSTRACT FROM AUTHOR]

Objective: To conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of perioperative insulin infusion on outcomes important to patients.Patients and Methods: We used 6 search strategies including an electronic database search of MEDLINE, EMBASE, and Cochrane CENTRAL, from their inception up to May 1, 2006, and included RCTs of perioperative insulin infusion (with or without glucose targets) measuring outcomes in patients undergoing any surgery. Pairs of reviewers working independently assessed the methodological quality and characteristics of included trials and abstracted data on perioperative outcomes (ie, outcomes that occurred during hospitalization or within 30 days of surgery).Results: We identified 34 eligible trials. In the 14 trials that assessed mortality, there were 68 deaths among 2192 patients randomized to insulin infusion compared with 98 deaths among 2163 patients randomized to control therapy (random-effects pooled relative risk, 0.69; 95% confidence interval [CI], 0.51-0.94; 99% CI, 0.46-1.04; I2, 0%; 95% CI, 0.0%-47.4%). Hypoglycemia increased in the intensively treated group (20 trials, 119/1470 patients in insulin infusion vs 48/1476 patients in control group; relative risk, 2.07; 95% CI, 1.29-3.32; 99% CI, 1.09-3.88; I2, 31.5%; 95% CI, 0.0%-59.0%). No significant effect was seen in any other outcomes. The available mortality data represent only 40% of the optimal information size required to reliably detect a plausible treatment effect; potential methodological and reporting biases weaken inferences.Conclusion: Perioperative insulin infusion may reduce mortality but increases hypoglycemia in patients who are undergoing surgery; however, mortality results require confirmation in large and rigorous RCTs. [ABSTRACT FROM AUTHOR]

In comparative effectiveness research Simulated Treatment Comparisons (STCs) are becoming increasingly common in the absence of head-to-head trials. STCs use estimates from limited IPD to adjust for covariate imbalance between trials, however the uncertainty from these estimates is generally ignored when estimating relative treatment effects. Conclusions Failing to account for uncertainty from covariate adjustment when conducting simulated treatment comparisons generally leads to underestimating the uncertainty of relative treatment effects. [Extracted from the article]