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�� We will grade the quality of included studies and risk of bias using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool28 with GRADEprofiler (GRADEpro) V.3.6 software. Any disagreements will be resolved by discussion with ZL. Measures of treatment effect For continuous data, the mean difference (MD) will be used to measure treatment effect with 95% CIs. In case outcome variables have different scales, the standardised ZD6474 chemical structure mean difference will be used with 95% CIs. For dichotomous data, treatment effects are presented as a risk ratio (RR) with 95% CIs. Other binary data will be changed into the RR form. Unit of analysis issues The unit of analysis will be each patient recruited into the trials. Dealing with missing data For each included ON-01910 price study, the number of dropouts, exclusions from the analysis and missing data will be gathered by contacting the study author. If we fail to obtain sufficient data, we will assume dichotomous outcomes for patients not experiencing any change in their clinical outcome variables. We will then perform sensitivity analyses to assess how sensitive the results are to changes in the assumptions made. If necessary, the potential impact of missing data on the findings of the review will be described in the ��Discussion�� section. Assessment of heterogeneity Cochran's Q test29 will be performed for the detection of heterogeneity. The I? statistic will be used to measure heterogeneity among the trials in each analysis. An I? value of 50% or more indicates a substantial level of inconsistency. If we identify substantial heterogeneity, we will report it and explore possible causes using subgroup analyses. Assessment of reporting biases If we are able to pool data from more than 10 trials TRIB1 for the primary outcome, a funnel plot will be created and examined to explore possible small study biases. We will interpret results carefully based on several explanations for funnel plot asymmetry. Data synthesis If two or more eligible RCTs are identified, meta-analyses will be performed with Review Manager 5.3. Whether a fixed effects model or a random effects model will be used depends on the results of the ��2 test and I2 test for heterogeneity. If substantial statistical heterogeneity is found, we will adopt a random effects model. If no substantial statistical heterogeneity is detected (I?