Systematic searches resulted in 178 references from PubMed, 42 from Embase, and 93 from the Cochrane Central Register. Of these 313 references, 100 were duplicates. A manual search resulted in 3 additional articles bringing the total to 216. After cross-referencing between investigators, 35 were then selected for a detailed review and analysis. From these, 23 were chosen for inclusion in the meta-analysis. In five of these studies, additional data were needed on the primary outcome of a subset of the participants. We obtained additional data from the authors in four of these studies. Because we did not obtain a response from the fifth author [30], we were unable to include their trial. The final selection procedure thus allowed us to analyze 22 studies (Figure 1).
