The meta-analysis, using a random effects model, produced a statistically significant summary effect measure of 17% excess risk (95% CI, 2 34) [(Table 2, Figure 1; see also Supplemental Material 1, Table 1, available online (doi 10.1289/ehp. 0900677.S1 via http://dx.doi.org/)].
Overall, 30 (63%) of the 48 meta-analyses of observational studies reported a nominally statistically significant summary result (tables 1 and 2). Figure 3 shows a forest plot with the summary effects of all the non-overlapping meta-analyses of observational studies (for binary outcomes).
The European studies had a summary risk estimate of 1.00 per 1 kg increase in weight (95% CI: 0.99 1.01, P=0.643) with an I 2 value for between-study heterogeneity of 58%, whereas North-American studies produced a borderline statistically significant summary estimate of 1.01 per 1 kg increase in weight (95% CI: 1.00 1.01, P=0.001) with an I 2 value of 0%.
However, meta-analyses of randomised controlled trials reported a nominally statistically significant summary result for only 13 of the 57 outcomes, and the confidence intervals of the estimates were generally wider than the confidence intervals of the meta-analyses of observational studies.
When we combined studies by country of origin, the six studies from the USA gave a summary OR of 0.94 (95% CI: 0.82 1.1), whereas the other three studies (from Canada, England, and New Zealand) gave a lower and statistically significant summary OR of 0.85 (95% CI: 0.76 0.96).
For major outcomes that showed significant summary beneficial effect of zinc on diarrhea, and which showed large heterogeneity across trials, we investigated the potential contributors to the heterogeneity.
Although this may be a routine procedure in the analysis of dose-response relationships, 15 some of the marginally significant summary HR should be interpreted with caution.
Fit is indicated by a non-significant summary chi-square statistic.
Pooled analysis of these seven studies showed a non-significant summary estimate favouring early RRT (OR 0.62, 95% CI 0.34 to 1.13, I2 = 69.6%; Figure 4).
There was also a significant reduction in summary score for pain between baseline and end of treatment (p < 0.001) and at follow-up (p < 0.001).
