A meta-analysis of the effects of probiotics and synbiotics in children with acute diarrhea

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Rationale
3 Describe the rationale for the review in the context of what is already known.

3
Objectives 4 Provide an explicit statement of the questions being addressed with reference, as applicable, to participants, interventions, comparisons, outcomes and study design (PICOS). Include any hypotheses that relate to particular types of participant-level subgroups. 3

Protocol and registration 5
Indicate if a protocol exists and where it can be accessed. If available, provide registration information including registration number and registry name. Provide publication details, if applicable.
Not publishe d Eligibility criteria 6 Specify inclusion and exclusion criteria including those relating to participants, interventions, comparisons, outcomes, study design and characteristics (e.g. years when conducted, required minimum follow-up). Note whether these were applied at the study or individual level i.e. whether eligible participants were included (and ineligible participants excluded) from a study that included a wider population than specified by the review inclusion criteria. The rationale for criteria should be stated.

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Study selection processes 9 State the process for determining which studies were eligible for inclusion.

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Data collection processes 10 Describe method of data extration collected and managed, including any processes for querying and confirming data with investigators.

5
This should include whether, how and what aggregate data were sought or extracted from study reports and publications (such as extracting data independently in duplicate) and any processes for obtaining and confirming these data with investigators.

Data items 11
Describe how the information and variables to be collected were chosen. List and define all study level and participant level data that were sought, including baseline and follow-up information. If applicable, describe methods of standardising or translating variables within the datasets to ensure common scales or measurements across studies.

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Risk of bias assessment 12 Describe methods used to assess risk of bias in the individual studies and whether this was applied separately for each outcome. If applicable, describe how findings of data checking were used to inform the assessment. Report if and how risk of bias assessment was used in any data synthesis.

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Specification of outcomes and effect measures 13 State all treatment comparisons of interests. State all outcomes addressed and define them in detail. State whether they were pre-specified for the review and, if applicable, whether they were primary/main or secondary/additional outcomes. Give the principal measures of effect (such as risk ratio, hazard ratio, difference in means) used for each outcome.

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Describe the meta-analysis methods used to conduct. Specify any statistical methods and models used. Issues should include (but are not restricted to):  Use of a one-stage or two-stage approach.  How effect estimates were generated separately within each study and combined across studies (where applicable).  Specification of one-stage models (where applicable) including how clustering of patients within studies was accounted for.  Use of fixed or random effects models and any other model assumptions, such as proportional hazards.  How (summary) survival curves were generated (where applicable).  Methods for quantifying statistical heterogeneity (such as I 2 and  2 ).  How missing data within dealt with (where applicable).

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Risk of bias across studies 15 Specify any assessment of risk of bias relating to the accumulated body of evidence.

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Additional analyses 16 Describe methods of any additional analyses, including sensitivity analyses. State which of these were pre-specified.

Study selection 17
Give numbers of studies screened, assessed for eligibility, and included in the systematic review with reasons for exclusions at each stage. Indicate the number of studies and participants . For those studies give the numbers of studies and participants for which aggregate data were available. Report reasons for non-availability. Include a flow diagram.

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For each study, present information on key study and participant characteristics (such as description of interventions, numbers of participants, demographic data, unavailability of outcomes, funding source, and if applicable duration of follow-up). Provide (main) citations for each study. 7; Table  1;

Risk of bias within studies 19
Present data on risk of bias assessments. If applicable, describe whether data checking led to the up-weighting or downweighting of these assessments. Consider how any potential bias impacts on the robustness of meta-analysis conclusions.

7; Fig 2
Results of studies 20 For each comparison and for each main outcome (benefit or harm), report the number of eligible participants for which data were obtained and show simple summary data for each intervention group (including, where applicable, the number of events), effect estimates and confidence intervals. These may be tabulated or included on a forest plot.  Table 2; Results of syntheses 21 Present summary effects for each meta-analysis undertaken, including confidence intervals and measures of statistical heterogeneity. State whether the analysis was pre-specified, and report the numbers of studies and participants and, where applicable, the number of events on which it is based.

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When exploring variation in effects due to patient or study characteristics, present summary interaction estimates for each characteristic examined, including confidence intervals and measures of statistical heterogeneity. State whether the analysis was pre-specified. State whether any interaction is consistent across trials.

Risk of bias across studies 22
Present results of any assessment of risk of bias relating to the accumulated body of evidence, including any pertaining to the availability and representativeness of available studies, outcomes or other variables.

Summary of evidence 24
Summarise the main findings, including the strength of evidence for each main outcome.

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Strengths and limitations 25 Discuss any important strengths and limitations of the evidence including the benefits of access to IPD and any limitations arising from IPD that were not available.

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Conclusions 26 Provide a general interpretation of the findings in the context of other evidence.

Funding 27
Describe sources of funding and other support (such as supply of IPD), and the role in the systematic review of those providing such support.