35 Risk factors: a systematic review 2 (GRADE) tool.36 This tool is recommended by the Cochrane Prognosis Methods Group.35 The GRADE includes a synthesis of results (combined number of participants, studies, cohort phase study and either a positive, negative or no effect) and scores each factor of the GRADE framework: (a) study limitations, (b) inconsistency, (c) indirectness, (d) imprecision, (e) publication bias, (f) effect sizes, and (g) dose effect. See Supplemental Table 3 for definitions and application of the GRADE domains. All evidence for each PICO (Supplemental Table 1) was independently assessed by Annelienke M. van Hulst and Shosha H.M. Peersmann. Besides the predefined PICOs, we also identified new risk factors from literature. Taking into account the combined GRADE synthesis and ratings, the overall level and quality of evidence was determined: + very low, ++ low, +++ moderate, or ++++ high quality. Individual synthesis and ratings (Annelienke M. van Hulst and Shosha H.M. Peersmann) were discussed until consensus was reached. If necessary, a third reviewer was consulted (Raphaële R. L. van Litsenburg). The results of the grading provide an overview of the results per risk factor and the (gaps of) evidence for each risk factor of developing either APRs or sleep problems.
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