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study appraisal and synthesis methods; results; limitations; conclusions and implications of key findings; systematic review registration number. 2INTRODUCTION Rationale 3Describe the rationale for the review in the context of what is already known. 3Objectives 4Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS). 4METHODS Protocol and registration 5Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number. 1Eligibility criteria 6Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale. 4Information sources 7Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched. 3Search 8Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated. 3Study selection 9State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis). 4Data collection process 10Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators. 4Data items 11List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made. 4Risk of bias in individual studies 12Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis. 4Summary measures 13State the principal summary measures (e.g., risk ratio, difference in means). 4Synthesis of results 14Describe the methods of handling data and combining results of studies, if done, including measures of consistency (e.g., I2) for each meta-analysis. 4 Page 1 of 2 Section/topic #Checklist item Reported on page # Risk of bias across studies 15Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies). 4Additional analyses 16Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified. 4RESULTS Study selection 17Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram. 4Study characteristics 18For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations. 5, Online only Table 1Risk of bias within studies 19Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12). 6Results of individual studies 20For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group (b) effect estimates and confidence intervals, ideally with a forest plot. 5, Figure 2Synthesis of results 21Present results of each meta-analysis done, including confidence intervals and measures of consistency. 5, Figure 2 & 3, Table 2Risk of bias across studies 22Present results of any assessment of risk of bias across studies (see Item 15). 6Additional analysis 23Give results of additional analyses, if done (e.g., sensitivity or subgroup analyses, meta-regression [see Item 16]). 5 & 6DISCUSSION Summary of evidence 24Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers). 6Limitations 25Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of identified research, reporting bias). 6 & 7Conclusions 26Provide a general interpretation of the results in the context of other evidence, and implications for future research. 7FUNDING Funding 27Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the systematic review. 8 From: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). 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