In the absence of a satisfactory systematic review, we did our own evidence synthesis using the primary studies identi ed in AT9 and in the updated search. If the panel judged that the identi ed randomized controlled trials (RCTs) were inadequate, we expanded the search to include prospective cohort studies. Study Selection, Data Abstraction, and Data Analysis The criteria for selecting the evidence were based on the Population, Intervention, Comparator, Outcome elements of the standardized questions and the study design (e-Table 2). We followed standard processes (duplicate independent work with agreement checking and disagreement resolution) for title and abstract screening, full text screening, data abstraction, and risk of bias assessment. We abstracted data on the characteristics of: study design, participants, intervention, control, outcomes, funding, and COI. We assessed risk of bias using the Cochrane Risk of Bias Tool in randomized trials4 and an adapted tool for observational studies5 (e-Table 3). When existing systematic reviews were not available or were inadequate, we performed meta-analyses when appropriate. For each outcome of interest, we calculated the risk ratios of individual studies then pooled them and assessed statistical heterogeneity using the I2 statistic. We used a xed-effects model when pooling data from two trials, or when one of the included trials was large relative to the others. Otherwise, we used a random-effects model. We used Review Manager software (version 5.2) to perform the meta-analyses and construct forest plots. We calculated absolute effects by applying pooled relative risks to baseline risks, ideally estimated from valid prognostic observational data or, in the absence of the latter, from control group risks. When credible data from prognostic observational studies were not available, we used risk estimates from control groups of RCTs included in the meta-analyses (e-Figures 5 and 6). 