Background We sought to assess the relative effects of individual anaplastic lymphoma kinase (ALK) inhibitors for the treatment of non-small cell lung cancer (NSCLC). Methods We searched MEDLINE, Embase, Cochrane CENTRAL, and grey literature (July 23, 2019) for randomized controlled trials (RCTs) that included participants with ALK-or ROS1-positive NSCLC who received any ALK inhibitor compared with placebo, another ALK inhibitor, or the same ALK inhibitor at a different dose. The primary outcome was treatment-related death. Secondary outcomes were overall survival (OS), progression-free survival (PFS), and serious adverse events. Data were pooled via meta-analysis and network meta-analysis, and risk of bias was assessed. PROSPERO: CRD42017077046. Results Thirteen RCTs reporting outcomes of interest among participants with ALK-positive NSCLC were identified. Treatment-related deaths were rare, with 10 deaths attributed to crizotinib (risk difference v. chemotherapy: 0.49, 95% credible interval [CrI]-0.16 to 1.46; odds ratio 2.58 (0.76-11.37). All ALK inhibitors improved PSF relative to chemotherapy (hazard ratio [95%

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)

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