The aim of this study is to systematically review and critically assess analytical observational epidemiology studies investigating the association between levels of drinking water hardness and cardiovascular disease. We searched electronic databases and used standardised forms to extract data and assess study quality. Of 2,906 papers identified, 14 met the inclusion criteria (nine case control and five cohort studies). Of the nine case control studies, seven examined both drinking water magnesium and calcium and risk of death from cardiovascular disease. A pooled odds ratio showed a statistically significant inverse association between magnesium and cardiovascular mortality (OR 0.75 (95%CI 0.68, 0.82), p , 0.001). Only two studies reported a statistically significant effect for calcium. Substantial heterogeneity between studies made calculation of a summary estimate for drinking water calcium inappropriate. Of three cohort studies reviewed, two were of good quality. A weak suggestion that soft water was harmful in females and possibly associated with a slightly greater risk of sudden death was reported, but there was no association between water hardness and mortality from stroke or cardiovascular disease. This study found significant evidence of an inverse association between magnesium levels in drinking water and cardiovascular mortality following a meta-analysis of case control studies. Evidence for calcium remains unclear.

This paper presents the results of a meta-analysis of published transfer rates of antimicrobial resistance genes. A total of 34 papers were identified, of which 28 contained rates estimated in relation to either donor or recipient bacterial counts. The published rates ranged from 10 ؊2 to 10 ؊9. Generalized linear modeling was conducted to identify the factors influencing this variation. Highly significant associations between transfer frequency and both the donor (P ‫؍‬ 1.2 ؋ 10 ؊4 ) and recipient (P ‫؍‬ 1.0 ؋ 10 ؊5 ) genera were found. Also significant was whether the donor and recipient strains were of the same genus (P ‫؍‬ 0.023) and the nature of the genetic element (P ‫؍‬ 0.0019). The type of experiment, in vivo or in vitro, approached statistical significance (P ‫؍‬ 0.12). Parameter estimates from a general linear model were used to estimate the probability of transfer of antimicrobial resistance genes to potential pathogens in the intestine following oral ingestion. The mean logarithms of these probabilities are in the range of [؊7.0, ؊3.1]. These probability distributions are suitable for use in the quantitative assessment of the risk of transfer of antimicrobial resistance genes to the intestinal flora of humans and animals.

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