The contours help to indicate whether areas of the plot, where studies are perceived to be missing, are where studies would have statistically significant effect sizes or not and thus decrease or increase the AS 1892802 evidence that the asymmetry is due to publication bias. The presence of funnel plot asymmetry was also assessed using Egger��s test. To adjust for the impact of publication bias on the pooled effect estimate, we used a novel regression based adjustment method recently suggested by Moreno et al. An adjusted pooled effect estimate for an ideal study of a very large size is obtained from the fitted weighted linear regression equation, plotted with a regression line on the contour enhanced funnel plot. This method of regression is a modified version of conventional Egger��s regression test for publication bias where the log of effect estimate is regressed by its variance rather than the standard error and weights are assigned according to the inverse of the variance. This model has been shown to consistently outperform the conventional trim and fill method. Finally, the possible influence of unknown confounders was CD 2665 investigated with a rule-out approach described by Schneeweiss. This approach stipulates the influence of a hypothetical confounder and determines what characteristics this confounder must have to fully account for the observed association between use of PPIs and occurrence of CDI. The hypothetical confounder is characterized by its association to PPIs use and its association to the outcome. For this analysis, the absolute risk in the pooled nonexposed group was used for conversion of odds ratio to relative risk using the method described by Zhang and Yu. Finally, we interpret the results in the context of observed limitations and therefore, draw more careful conclusions. Contrary to other reviews and FDA alert, we conclude that current cumulative data constitutes very low quality evidence. Our results are helpful for guidelines writing committees and policy makers that use the GRADE framework when formulating recommendations for use of PPI for different clinical indications. It has been proposed that the vegetative form of C. difficile, which is killed by acid, plays a role in pathogenesis. Vegetative forms survive on surfaces and could be ingested by patients. Survival of these acid-sensitive vegetative forms in the stomach could be facilitated by 2 main factors: suppression of gastric acid production by acid-suppressive medications; and presence of bile salts in gastric contents of patients on acid-suppressive therapy. Bile salts, which are mainly found in the small intestine, are present in gastric contents, particularly among patients with gastro-esophageal reflux disease. Moreover, PPI use can delay gastric emptying and predispose to bacterial overgrowth with associated high intragastric bile salts which could trigger spore germination in the stomach. However, a recent in vitro experiment has challenged these postulated biological mechanisms for the observed association. In this experiment, aspirate of gastric contents from hospitalized patients with nasogastric tubes were collected.