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Background: Extreme temperatures contribute significantly to global mortality. While previous studies on temperature and stroke-specific outcomes presented conflicting results, these studies were predominantly limited to single-city or single-country analyses. Their findings are difficult to synthesize due to variations in methodologies and exposure definitions., Methods: Within the Multi-Country Multi-City Network, we built a new mortality database for ischemic and hemorrhagic stroke. Applying a unified analysis protocol, we conducted a multinational case-crossover study on the relationship between extreme temperatures and stroke. In the first stage, we fitted a conditional quasi-Poisson regression for daily mortality counts with distributed lag nonlinear models for temperature exposure separately for each city. In the second stage, the cumulative risk from each city was pooled using mixed-effect meta-analyses, accounting for clustering of cities with similar features. We compared temperature-stroke associations across country-level gross domestic product per capita. We computed excess deaths in each city that are attributable to the 2.5% hottest and coldest of days based on each city's temperature distribution., Results: We collected data for a total of 3 443 969 ischemic strokes and 2 454 267 hemorrhagic stroke deaths from 522 cities in 25 countries. For every 1000 ischemic stroke deaths, we found that extreme cold and hot days contributed 9.1 (95% empirical CI, 8.6-9.4) and 2.2 (95% empirical CI, 1.9-2.4) excess deaths, respectively. For every 1000 hemorrhagic stroke deaths, extreme cold and hot days contributed 11.2 (95% empirical CI, 10.9-11.4) and 0.7 (95% empirical CI, 0.5-0.8) excess deaths, respectively. We found that countries with low gross domestic product per capita were at higher risk of heat-related hemorrhagic stroke mortality than countries with high gross domestic product per capita ( P =0.02)., Conclusions: Both extreme cold and hot temperatures are associated with an increased risk of dying from ischemic and hemorrhagic strokes. As climate change continues to exacerbate these extreme temperatures, interventional strategies are needed to mitigate impacts on stroke mortality, particularly in low-income countries., Competing Interests: Disclosures Dr Garshick receives grant support from the US Department of Veterans Affairs and is an author for UpToDate. Dr Zanobetti receives grant support from the National Institutes of Health. Dr Bell receives grant support from US Environmental Protection Agency, National Institutes of Health, High Tide Foundation, Health Effects Institute, Yale Women Faculty Forum, Environmental Defense Fund, Wellcome Trust Foundation, Yale Climate Change and Health Center, Robert Wood Johnson Foundation, Hutchinson Postdoctoral Fellowship, and Institute of Physics. The other authors report no conflicts.

Background: Cardiovascular disease is the leading cause of death worldwide. Existing studies on the association between temperatures and cardiovascular deaths have been limited in geographic zones and have generally considered associations with total cardiovascular deaths rather than cause-specific cardiovascular deaths., Methods: We used unified data collection protocols within the Multi-Country Multi-City Collaborative Network to assemble a database of daily counts of specific cardiovascular causes of death from 567 cities in 27 countries across 5 continents in overlapping periods ranging from 1979 to 2019. City-specific daily ambient temperatures were obtained from weather stations and climate reanalysis models. To investigate cardiovascular mortality associations with extreme hot and cold temperatures, we fit case-crossover models in each city and then used a mixed-effects meta-analytic framework to pool individual city estimates. Extreme temperature percentiles were compared with the minimum mortality temperature in each location. Excess deaths were calculated for a range of extreme temperature days., Results: The analyses included deaths from any cardiovascular cause (32 154  935), ischemic heart disease (11 745 880), stroke (9 351 312), heart failure (3 673 723), and arrhythmia (670 859). At extreme temperature percentiles, heat (99th percentile) and cold (1st percentile) were associated with higher risk of dying from any cardiovascular cause, ischemic heart disease, stroke, and heart failure as compared to the minimum mortality temperature, which is the temperature associated with least mortality. Across a range of extreme temperatures, hot days (above 97.5th percentile) and cold days (below 2.5th percentile) accounted for 2.2 (95% empirical CI [eCI], 2.1-2.3) and 9.1 (95% eCI, 8.9-9.2) excess deaths for every 1000 cardiovascular deaths, respectively. Heart failure was associated with the highest excess deaths proportion from extreme hot and cold days with 2.6 (95% eCI, 2.4-2.8) and 12.8 (95% eCI, 12.2-13.1) for every 1000 heart failure deaths, respectively., Conclusions: Across a large, multinational sample, exposure to extreme hot and cold temperatures was associated with a greater risk of mortality from multiple common cardiovascular conditions. The intersections between extreme temperatures and cardiovascular health need to be thoroughly characterized in the present day-and especially under a changing climate.

Background: The association between fine particulate matter (PM2.5) and mortality widely differs between as well as within countries. Differences in PM2.5 composition can play a role in modifying the effect estimates, but there is little evidence about which components have higher impacts on mortality., Methods: We applied a 2-stage analysis on data collected from 210 locations in 16 countries. In the first stage, we estimated location-specific relative risks (RR) for mortality associated with daily total PM2.5 through time series regression analysis. We then pooled these estimates in a meta-regression model that included city-specific logratio-transformed proportions of seven PM2.5 components as well as meta-predictors derived from city-specific socio-economic and environmental indicators., Results: We found associations between RR and several PM2.5 components. Increasing the ammonium (NH4+) proportion from 1% to 22%, while keeping a relative average proportion of other components, increased the RR from 1.0063 (95% confidence interval [95% CI] = 1.0030, 1.0097) to 1.0102 (95% CI = 1.0070, 1.0135). Conversely, an increase in nitrate (NO3-) from 1% to 71% resulted in a reduced RR, from 1.0100 (95% CI = 1.0067, 1.0133) to 1.0037 (95% CI = 0.9998, 1.0077). Differences in composition explained a substantial part of the heterogeneity in PM2.5 risk., Conclusions: These findings contribute to the identification of more hazardous emission sources. Further work is needed to understand the health impacts of PM2.5 components and sources given the overlapping sources and correlations among many components., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Air conditioning has been proposed as one of the key factors explaining reductions of heat-related mortality risks observed in the last decades. However, direct evidence is still limited., Methods: We used a multi-country, multi-city, longitudinal design to quantify the independent role of air conditioning in reported attenuation in risk. We collected daily time series of mortality, mean temperature, and yearly air conditioning prevalence for 311 locations in Canada, Japan, Spain, and the USA between 1972 and 2009. For each city and sub-period, we fitted a quasi-Poisson regression combined with distributed lag non-linear models to estimate summer-only temperature-mortality associations. At the second stage, we used a novel multilevel, multivariate spatio-temporal meta-regression model to evaluate effect modification of air conditioning on heat-mortality associations. We computed relative risks and fractions of heat-attributable excess deaths under observed and fixed air conditioning prevalences., Results: Results show an independent association between increased air conditioning prevalence and lower heat-related mortality risk. Excess deaths due to heat decreased during the study periods from 1.40% to 0.80% in Canada, 3.57% to 1.10% in Japan, 3.54% to 2.78% in Spain, and 1.70% to 0.53% in the USA. However, increased air conditioning explains only part of the observed attenuation, corresponding to 16.7% in Canada, 20.0% in Japan, 14.3% in Spain, and 16.7% in the USA., Conclusions: Our findings are consistent with the hypothesis that air conditioning represents an effective heat adaptation strategy, but suggests that other factors have played an equal or more important role in increasing the resilience of populations.

Reliable estimates of future health impacts due to climate change are needed to inform and contribute to the design of efficient adaptation and mitigation strategies. However, projecting health burdens associated to specific environmental stressors is a challenging task because of the complex risk patterns and inherent uncertainty of future climate scenarios. These assessments involve multidisciplinary knowledge, requiring expertise in epidemiology, statistics, and climate science, among other subjects. Here, we present a methodologic framework to estimate future health impacts under climate change scenarios based on a defined set of assumptions and advanced statistical techniques developed in time-series analysis in environmental epidemiology. The proposed methodology is illustrated through a step-by-step hands-on tutorial structured in well-defined sections that cover the main methodological steps and essential elements. Each section provides a thorough description of each step, along with a discussion on available analytical options and the rationale on the choices made in the proposed framework. The illustration is complemented with a practical example of study using real-world data and a series of R scripts included as Supplementary Digital Content; http://links.lww.com/EDE/B504, which facilitates its replication and extension on other environmental stressors, outcomes, study settings, and projection scenarios. Users should critically assess the potential modeling alternatives and modify the framework and R code to adapt them to their research on health impact projections.