Systematic review and meta-analysis of cohort studies of long term outdoor nitrogen dioxide exposure and mortality.

OBJECTIVE: To determine whether long term exposure to outdoor nitrogen dioxide (NO2) is associated with all-cause or cause-specific mortality. METHODS: MEDLINE, Embase, CENTRAL, Global Health and Toxline databases were searched using terms developed by a librarian. Screening, data extraction and risk of bias assessment were completed independently by two reviewers. Conflicts were resolved through consensus and/or involvement of a third reviewer. Pooling of results across studies was conducted using random effects models, heterogeneity among included studies was assessed using Cochran's Q and I2 measures, and sources of heterogeneity were evaluated using meta-regression. Sensitivity of pooled estimates to individual studies was examined and publication bias was evaluated using Funnel plots, Begg's and Egger's tests, and trim and fill. RESULTS: Seventy-nine studies based on 47 cohorts, plus one set of pooled analyses of multiple European cohorts, met inclusion criteria. There was a consistently high degree of heterogeneity. After excluding studies with probably high or high risk of bias in the confounding domain (n = 12), pooled hazard ratios (HR) indicated that long term exposure to NO2 was significantly associated with mortality from all/ natural causes (pooled HR 1.047, 95% confidence interval (CI), 1.023-1.072 per 10 ppb), cardiovascular disease (pooled HR 1.058, 95%CI 1.026-1.091), lung cancer (pooled HR 1.083, 95%CI 1.041-1.126), respiratory disease (pooled HR 1.062, 95%CI1.035-1.089), and ischemic heart disease (pooled HR 1.111, 95%CI 1.079-1.144). Pooled estimates based on multi-pollutant models were consistently smaller than those from single pollutant models and mostly non-significant. CONCLUSIONS: For all causes of death other than cerebrovascular disease, the overall quality of the evidence is moderate, and the strength of evidence is limited, while for cerebrovascular disease, overall quality is low and strength of evidence is inadequate. Important uncertainties remain, including potential confounding by co-pollutants or other concomitant exposures, and limited supporting mechanistic evidence. (PROSPERO registration number CRD42018084497).

The effects of resistant starches on inflammatory bowel disease in preclinical and clinical settings: a systematic review and meta-analysis.

BACKGROUND: Inflammatory bowel disease (IBD) is a debilitating chronic disease with limited treatment options. Resistant starches may represent a novel treatment for IBD. However, its efficacy and safety remain unclear. Our objective was to perform a systematic review to summarize the preclinical and clinical effects of resistant starch, which may help guide future studies. METHODS: Medline, EMBASE, and the Cochrane Central Register were searched. Included studies investigated the use of resistant starch therapy in in vivo animal models of IBD or human patients with IBD. Articles were screened, and data extracted, independently and in duplicate. The primary outcomes were clinical remission (clinical) and bowel mucosal damage (preclinical). RESULTS: 21 preclinical (n = 989 animals) and seven clinical (n = 164 patients) studies met eligibility. Preclinically, resistant starch was associated with a significant reduction in bowel mucosal damage compared to placebo (standardized mean difference - 1.83, 95% CI - 2.45 to - 1.20). Clinically, five studies reported data on clinical remission but clinical and methodological heterogeneity precluded pooling. In all five, a positive effect was seen in patients who consumed resistant starch supplemented diets. The majority of studies in both the preclinical and clinical settings were at a high or unclear risk of bias due to poor methodological reporting. CONCLUSIONS: Our review demonstrates that resistant starch is associated with reduced histology damage in animal studies, and improvements in clinical remission in IBD patients. These results need to be tempered by the risk of bias of included studies. Rigorously designed preclinical and clinical studies are warranted. Trial registration The review protocols were registered on PROSPERO (preclinical: CRD42019130896; clinical: CRD42019129513).

Correction to: Systematic review and meta-analysis of case-crossover and time-series studies of short term outdoor nitrogen dioxide exposure and ischemic heart disease morbidity.

An amendment to this paper has been published and can be accessed via the original article.

Systematic review and meta-analysis of case-crossover and time-series studies of short term outdoor nitrogen dioxide exposure and ischemic heart disease morbidity.

BACKGROUND: Nitrogen dioxide (NO2) is a pervasive urban pollutant originating primarily from vehicle emissions. Ischemic heart disease (IHD) is associated with a considerable public health burden worldwide, but whether NO2 exposure is causally related to IHD morbidity remains in question. Our objective was to determine whether short term exposure to outdoor NO2 is causally associated with IHD-related morbidity based on a synthesis of findings from case-crossover and time-series studies. METHODS: MEDLINE, Embase, CENTRAL, Global Health and Toxline databases were searched using terms developed by a librarian. Screening, data extraction and risk of bias assessment were completed independently by two reviewers. Conflicts between reviewers were resolved through consensus and/or involvement of a third reviewer. Pooling of results across studies was conducted using random effects models, heterogeneity among included studies was assessed using Cochran's Q and I2 measures, and sources of heterogeneity were evaluated using meta-regression. Sensitivity of pooled estimates to individual studies was examined using Leave One Out analysis and publication bias was evaluated using Funnel plots, Begg's and Egger's tests, and trim and fill. RESULTS: Thirty-eight case-crossover studies and 48 time-series studies were included in our analysis. NO2 was significantly associated with IHD morbidity (pooled odds ratio from case-crossover studies: 1.074 95% CI 1.052-1.097; pooled relative risk from time-series studies: 1.022 95% CI 1.016-1.029 per 10 ppb). Pooled estimates for case-crossover studies from Europe and North America were significantly lower than for studies conducted elsewhere. The high degree of heterogeneity among studies was only partially accounted for in meta-regression. There was evidence of publication bias, particularly for case-crossover studies. For both case-crossover and time-series studies, pooled estimates based on multi-pollutant models were smaller than those from single pollutant models, and those based on older populations were larger than those based on younger populations, but these differences were not statistically significant. CONCLUSIONS: We concluded that there is a likely causal relationship between short term NO2 exposure and IHD-related morbidity, but important uncertainties remain, particularly related to the contribution of co-pollutants or other concomitant exposures, and the lack of supporting evidence from toxicological and controlled human studies.