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Figure 1.

Flow diagram of eligible studies.

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Table 1.

Characteristics of the included studies.

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Table 2.

The Association between H2RAs use and development of Clostridium difficile infection from case-control studies.

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Table 3.

The Association between H2RAs use and development of Clostridium difficile infection from cohort studies.

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Table 4.

Modified Newcastle-Ottawa quality assessment scale for case-control studies included in the meta-analysis.

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Table 5.

Modified Newcastle-Ottawa Quality Assessment Scale for Cohort studies included in the Meta-analysis

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Figure 2.

Forest plot-random effect model meta-analysis of the association between CDI and H2RAs based on 35 observations stratified by country.

Error bars indicate confidence interval.

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Figure 3.

Forest plot of the pooled proportion of Clostridium difficile cases that were exposed to antibiotics.

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Table 6.

Influence of study type and country on the pooled effect estimate and its associated heterogeneity.

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Table 7.

Meta-regression analysis to explore sources of heterogeneity.

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Figure 4.

Contour-enhanced funnel plot

of the association between the estimated effect size and its standard error in all studies comparing those exposed and unexposed to H2RA displays areas of statistical significance on a funnel plot. Contours represent conventional “milestone” levels of statistical significance (e.g., <0.01, <0.05, <0.1). This funnel plot is symmetrical as it is not missing studies in the white area excluding the possibility of publication bias (Egger's test, p = 0.905).

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Figure 5.

Influence of a hypothetical dichotomous confounder present in 20% (panel A) and 40% (panel B) of the study population, unaccounted for in prior adjustments performed in individual studies.

The graphs depict what combinations of OREC and RR would be necessary for the confounder to fully account for the observed association between H2RA use and CDI acquisition. Abbreviations: OREC, odds ratio of exposure to the confounder in H2RA non-users vs. H2RA users; RRCD, relative risk of CDAD in individuals exposed to the confounder vs. non-exposed.

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