Associations Between Extreme Temperatures and Cardiovascular Cause-Specific Mortality: Results From 27 Countries.

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.

Extreme Temperatures and Stroke Mortality: Evidence From a Multi-Country Analysis.

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.

Tropical cyclone-specific mortality risks and the periods of concern: A multicountry time-series study.

BACKGROUND: More intense tropical cyclones (TCs) are expected in the future under a warming climate scenario, but little is known about their mortality effect pattern across countries and over decades. We aim to evaluate the TC-specific mortality risks, periods of concern (POC) and characterize the spatiotemporal pattern and exposure-response (ER) relationships on a multicountry scale. METHODS AND FINDINGS: Daily all-cause, cardiovascular, and respiratory mortality among the general population were collected from 494 locations in 18 countries or territories during 1980 to 2019. Daily TC exposures were defined when the maximum sustained windspeed associated with a TC was ≥34 knots using a parametric wind field model at a 0.5° × 0.5° resolution. We first estimated the TC-specific mortality risks and POC using an advanced flexible statistical framework of mixed Poisson model, accounting for the population changes, natural variation, seasonal and day of the week effects. Then, a mixed meta-regression model was used to pool the TC-specific mortality risks to estimate the overall and country-specific ER relationships of TC characteristics (windspeed, rainfall, and year) with mortality. Overall, 47.7 million all-cause, 15.5 million cardiovascular, and 4.9 million respiratory deaths and 382 TCs were included in our analyses. An overall average POC of around 20 days was observed for TC-related all-cause and cardiopulmonary mortality, with relatively longer POC for the United States of America, Brazil, and Taiwan (>30 days). The TC-specific relative risks (RR) varied substantially, ranging from 1.04 to 1.42, 1.07 to 1.77, and 1.12 to 1.92 among the top 100 TCs with highest RRs for all-cause, cardiovascular, and respiratory mortality, respectively. At country level, relatively higher TC-related mortality risks were observed in Guatemala, Brazil, and New Zealand for all-cause, cardiovascular, and respiratory mortality, respectively. We found an overall monotonically increasing and approximately linear ER curve of TC-related maximum sustained windspeed and cumulative rainfall with mortality, with heterogeneous patterns across countries and regions. The TC-related mortality risks were generally decreasing from 1980 to 2019, especially for the Philippines, Taiwan, and the USA, whereas potentially increasing trends in TC-related all-cause and cardiovascular mortality risks were observed for Japan. CONCLUSIONS: The TC mortality risks and POC varied greatly across TC events, locations, and countries. To minimize the TC-related health burdens, targeted strategies are particularly needed for different countries and regions, integrating epidemiological evidence on region-specific POC and ER curves that consider across-TC variability.

Global, regional, and national burden of heatwave-related mortality from 1990 to 2019: A three-stage modelling study.

BACKGROUND: The regional disparity of heatwave-related mortality over a long period has not been sufficiently assessed across the globe, impeding the localisation of adaptation planning and risk management towards climate change. We quantified the global mortality burden associated with heatwaves at a spatial resolution of 0.5°×0.5° and the temporal change from 1990 to 2019. METHODS AND FINDINGS: We collected data on daily deaths and temperature from 750 locations of 43 countries or regions, and 5 meta-predictors in 0.5°×0.5° resolution across the world. Heatwaves were defined as location-specific daily mean temperature ≥95th percentiles of year-round temperature range with duration ≥2 days. We first estimated the location-specific heatwave-mortality association. Secondly, a multivariate meta-regression was fitted between location-specific associations and 5 meta-predictors, which was in the third stage used with grid cell-specific meta-predictors to predict grid cell-specific association. Heatwave-related excess deaths were calculated for each grid and aggregated. During 1990 to 2019, 0.94% (95% CI: 0.68-1.19) of deaths [i.e., 153,078 cases (95% eCI: 109,950-194,227)] per warm season were estimated to be from heatwaves, accounting for 236 (95% eCI: 170-300) deaths per 10 million residents. The ratio between heatwave-related excess deaths and all premature deaths per warm season remained relatively unchanged over the 30 years, while the number of heatwave-related excess deaths per 10 million residents per warm season declined by 7.2% per decade in comparison to the 30-year average. Locations with the highest heatwave-related death ratio and rate were in Southern and Eastern Europe or areas had polar and alpine climates, and/or their residents had high incomes. The temporal change of heatwave-related mortality burden showed geographic disparities, such that locations with tropical climate or low incomes were observed with the greatest decline. The main limitation of this study was the lack of data from certain regions, e.g., Arabian Peninsula and South Asia. CONCLUSIONS: Heatwaves were associated with substantial mortality burden that varied spatiotemporally over the globe in the past 30 years. The findings indicate the potential benefit of governmental actions to enhance health sector adaptation and resilience, accounting for inequalities across communities.

Cooling cities through urban green infrastructure: a health impact assessment of European cities.

BACKGROUND: High ambient temperatures are associated with many health effects, including premature mortality. The combination of global warming due to climate change and the expansion of the global built environment mean that the intensification of urban heat islands (UHIs) is expected, accompanied by adverse effects on population health. Urban green infrastructure can reduce local temperatures. We aimed to estimate the mortality burden that could be attributed to UHIs and the mortality burden that would be prevented by increasing urban tree coverage in 93 European cities. METHODS: We did a quantitative health impact assessment for summer (June 1-Aug 31), 2015, of the effect of UHIs on all-cause mortality for adults aged 20 years or older in 93 European cities. We also estimated the temperature reductions that would result from increasing tree coverage to 30% for each city and estimated the number of deaths that could be potentially prevented as a result. We did all analyses at a high-resolution grid-cell level (250 × 250 m). We propagated uncertainties in input analyses by using Monte Carlo simulations to obtain point estimates and 95% CIs. We also did sensitivity analyses to test the robustness of our estimates. FINDINGS: The population-weighted mean city temperature increase due to UHI effects was 1·5°C (SD 0·5; range 0·5-3·0). Overall, 6700 (95% CI 5254-8162) premature deaths could be attributable to the effects of UHIs (corresponding to around 4·33% [95% CI 3·37-5·28] of all summer deaths). We estimated that increasing tree coverage to 30% would cool cities by a mean of 0·4°C (SD 0·2; range 0·0-1·3). We also estimated that 2644 (95% CI 2444-2824) premature deaths could be prevented by increasing city tree coverage to 30%, corresponding to 1·84% (1·69-1·97) of all summer deaths. INTERPRETATION: Our results showed the deleterious effects of UHIs on mortality and highlighted the health benefits of increasing tree coverage to cool urban environments, which would also result in more sustainable and climate-resilient cities. FUNDING: GoGreenRoutes, Spanish Ministry of Science and Innovation, Institute for Global Health, UK Medical Research Council, European Union's Horizon 2020 Project Exhaustion.

Exploring the nexus of urban form, transport, environment and health in large-scale urban studies: A state-of-the-art scoping review.

BACKGROUND: As the world becomes increasingly urbanised, there is recognition that public and planetary health relies upon a ubiquitous transition to sustainable cities. Disentanglement of the complex pathways of urban design, environmental exposures, and health, and the magnitude of these associations, remains a challenge. A state-of-the-art account of large-scale urban health studies is required to shape future research priorities and equity- and evidence-informed policies. OBJECTIVES: The purpose of this review was to synthesise evidence from large-scale urban studies focused on the interaction between urban form, transport, environmental exposures, and health. This review sought to determine common methodologies applied, limitations, and future opportunities for improved research practice. METHODS: Based on a literature search, 2958 articles were reviewed that covered three themes of: urban form; urban environmental health; and urban indicators. Studies were prioritised for inclusion that analysed at least 90 cities to ensure broad geographic representation and generalisability. Of the initially identified studies, following expert consultation and exclusion criteria, 66 were included. RESULTS: The complexity of the urban ecosystem on health was evidenced from the context dependent effects of urban form variables on environmental exposures and health. Compact city designs were generally advantageous for reducing harmful environmental exposure and promoting health, with some exceptions. Methodological heterogeneity was indicative of key urban research challenges; notable limitations included exposure and health data at varied spatial scales and resolutions, limited availability of local-level sociodemographic data, and the lack of consensus on robust methodologies that encompass best research practice. CONCLUSION: Future urban environmental health research for evidence-informed urban planning and policies requires a multi-faceted approach. Advances in geospatial and AI-driven techniques and urban indicators offer promising developments; however, there remains a wider call for increased data availability at local-levels, transparent and robust methodologies of large-scale urban studies, and greater exploration of urban health vulnerabilities and inequities.

Child Survival and Annual Crop Yield Reductions in Rural Burkina Faso: Critical Windows of Vulnerability Around Early-Life Development.

Populations that are reliant on subsistence farming are particularly vulnerable to climatic effects on crop yields. However, empirical evidence on the role of the timing of exposure to crop yield deficits in early-life development is limited. We examined the relationship between child survival and annual crop yield reductions at different stages of early-life development in a subsistence farming population in Burkina Faso. Using shared frailty Cox proportional hazards models adjusting for confounders, we analyzed 57,288 children under 5 years of age followed by the Nouna Health and Demographic Surveillance System (1994-2016) in relation to provincial food-crop yield levels experienced in 5 nonoverlapping time windows (12 months before conception, gestation, birth-age 5.9 months, ages 6.0 months-1.9 years, and ages 2.0-4.9 years) and their aggregates (birth-1.9 years, first 1,000 days from conception, and birth-4.9 years). Of the nonoverlapping windows, point estimates were largest for child survival related to food-crop yields for the time window of 6.0 months-1.9 years: The adjusted mortality hazard ratio was 1.10 (95% confidence interval: 1.03, 1.19) for a 90th-to-10th percentile yield reduction. These findings suggest that child survival in this setting is particularly vulnerable to cereal-crop yield reductions during the period of nonexclusive breastfeeding.

Asthma hospitalisations and heat exposure in England: a case-crossover study during 2002-2019.

BACKGROUND: Previous studies have reported an association between warm temperature and asthma hospitalisation. They have reported different sex-related and age-related vulnerabilities; nevertheless, little is known about how this effect has changed over time and how it varies in space. This study aims to evaluate the association between asthma hospitalisation and warm temperature and investigate vulnerabilities by age, sex, time and space. METHODS: We retrieved individual-level data on summer asthma hospitalisation at high temporal (daily) and spatial (postcodes) resolutions during 2002-2019 in England from the NHS Digital. Daily mean temperature at 1 km×1 km resolution was retrieved from the UK Met Office. We focused on lag 0-3 days. We employed a case-crossover study design and fitted Bayesian hierarchical Poisson models accounting for possible confounders (rainfall, relative humidity, wind speed and national holidays). RESULTS: After accounting for confounding, we found an increase of 1.11% (95% credible interval: 0.88% to 1.34%) in the asthma hospitalisation risk for every 1°C increase in the ambient summer temperature. The effect was highest for males aged 16-64 (2.10%, 1.59% to 2.61%) and during the early years of our analysis. We also found evidence of a decreasing linear trend of the effect over time. Populations in Yorkshire and the Humber and East and West Midlands were the most vulnerable. CONCLUSION: This study provides evidence of an association between warm temperature and hospital admission for asthma. The effect has decreased over time with potential explanations including temporal differences in patterns of heat exposure, adaptive mechanisms, asthma management, lifestyle, comorbidities and occupation.

Short-term exposure to ambient air pollution and individual emergency department visits for COVID-19: a case-crossover study in Canada.

BACKGROUND: Ambient air pollution is thought to contribute to increased risk of COVID-19, but the evidence is controversial. OBJECTIVE: To evaluate the associations between short-term variations in outdoor concentrations of ambient air pollution and COVID-19 emergency department (ED) visits. METHODS: We conducted a case-crossover study of 78 255 COVID-19 ED visits in Alberta and Ontario, Canada between 1 March 2020 and 31 March 2021. Daily air pollution data (ie, fine particulate matter with diameter less than 2.5 µm (PM2.5), nitrogen dioxide (NO2) and ozone were assigned to individual case of COVID-19 in 10 km × 10 km grid resolution. Conditional logistic regression was used to estimate associations between air pollution and ED visits for COVID-19. RESULTS: Cumulative ambient exposure over 0-3 days to PM2.5 (OR 1.010; 95% CI 1.004 to 1.015, per 6.2 µg/m3) and NO2 (OR 1.021; 95% CI 1.015 to 1.028, per 7.7 ppb) concentrations were associated with ED visits for COVID-19. We found that the association between PM2.5 and COVID-19 ED visits was stronger among those hospitalised following an ED visit, as a measure of disease severity, (OR 1.023; 95% CI 1.015 to 1.031) compared with those not hospitalised (OR 0.992; 95% CI 0.980 to 1.004) (p value for effect modification=0.04). CONCLUSIONS: We found associations between short-term exposure to ambient air pollutants and COVID-19 ED visits. Exposure to air pollution may also lead to more severe COVID-19 disease.

High Summer Temperatures and Heat Stroke Mortality in Spain.

BACKGROUND: Heat stroke is a significant cause of mortality in response to high summer temperatures. There is limited evidence on the pattern and magnitude of the association between temperature and heat stroke mortality. We examined this association in Spain, using data from a 27-year follow-up period. METHODS: We used a space-time-stratified case-crossover design. We analyzed data using conditional quasi-Poisson regression with distributed lag nonlinear models. RESULTS: Spain recorded a total of 285 heat stroke deaths between 1990 and 2016. Heat stroke deaths occurred in 6% of the days in the summer months. The mean temperature was, on average, 5 °C higher on days when a heat stroke was recorded than on days without heat stroke deaths. The overall relative risk was 1.74 (95% confidence interval = 1.54, 1.96) for a 1 °C rise in mean temperature above the threshold of 16 °C, at which a heat stroke death was first recorded. We observed lagged effects as long as 10 days. CONCLUSIONS: Although heat stroke represents a small fraction of total heat-attributable mortality during the summer, it is strongly associated with high temperatures, providing an immediately visible warning of heat-related risk.

Integrating Augmented In Situ Measurements and a Spatiotemporal Machine Learning Model To Back Extrapolate Historical Particulate Matter Pollution over the United Kingdom: 1980-2019.

Historical PM2.5 data are essential for assessing the health effects of air pollution exposure across the life course or early life. However, a lack of high-quality data sources, such as satellite-based aerosol optical depth before 2000, has resulted in a gap in spatiotemporally resolved PM2.5 data for historical periods. Taking the United Kingdom as an example, we leveraged the light gradient boosting model to capture the spatiotemporal association between PM2.5 concentrations and multi-source geospatial predictors. Augmented PM2.5 from PM10 measurements expanded the spatiotemporal representativeness of the ground measurements. Observations before and after 2009 were used to train and test the models, respectively. Our model showed fair prediction accuracy from 2010 to 2019 [the ranges of coefficients of determination (R2) for the grid-based cross-validation are 0.71-0.85] and commendable back extrapolation performance from 1998 to 2009 (the ranges of R2 for the independent external testing are 0.32-0.65) at the daily level. The pollution episodes in the 1980s and pollution levels in the 1990s were also reproduced by our model. The 4-decade PM2.5 estimates demonstrated that most regions in England witnessed significant downward trends in PM2.5 pollution. The methods developed in this study are generalizable to other data-rich regions for historical air pollution exposure assessment.

Coarse Particulate Air Pollution and Daily Mortality: A Global Study in 205 Cities.

Rationale: The associations between ambient coarse particulate matter (PM2.5-10) and daily mortality are not fully understood on a global scale. Objectives: To evaluate the short-term associations between PM2.5-10 and total, cardiovascular, and respiratory mortality across multiple countries/regions worldwide. Methods: We collected daily mortality (total, cardiovascular, and respiratory) and air pollution data from 205 cities in 20 countries/regions. Concentrations of PM2.5-10 were computed as the difference between inhalable and fine PM. A two-stage time-series analytic approach was applied, with overdispersed generalized linear models and multilevel meta-analysis. We fitted two-pollutant models to test the independent effect of PM2.5-10 from copollutants (fine PM, nitrogen dioxide, sulfur dioxide, ozone, and carbon monoxide). Exposure-response relationship curves were pooled, and regional analyses were conducted. Measurements and Main Results: A 10 µg/m3 increase in PM2.5-10 concentration on lag 0-1 day was associated with increments of 0.51% (95% confidence interval [CI], 0.18%-0.84%), 0.43% (95% CI, 0.15%-0.71%), and 0.41% (95% CI, 0.06%-0.77%) in total, cardiovascular, and respiratory mortality, respectively. The associations varied by country and region. These associations were robust to adjustment by all copollutants in two-pollutant models, especially for PM2.5. The exposure-response curves for total, cardiovascular, and respiratory mortality were positive, with steeper slopes at lower exposure ranges and without discernible thresholds. Conclusions: This study provides novel global evidence on the robust and independent associations between short-term exposure to ambient PM2.5-10 and total, cardiovascular, and respiratory mortality, suggesting the need to establish a unique guideline or regulatory limit for daily concentrations of PM2.5-10.

Non-optimal apparent temperature and cardiovascular mortality: the association in Puducherry, India between 2011 and 2020.

BACKGROUND: Cardiovascular diseases (CVDs), the leading cause of death worldwide, are sensitive to temperature. In light of the reported climate change trends, it is important to understand the burden of CVDs attributable to temperature, both hot and cold. The association between CVDs and temperature is region-specific, with relatively few studies focusing on low-and middle-income countries. This study investigates this association in Puducherry, a district in southern India lying on the Bay of Bengal, for the first time. METHODS: Using in-hospital CVD mortality data and climate data from the Indian Meteorological Department, we analyzed the association between apparent temperature (Tapp) and in-hospital CVD mortalities in Puducherry between 2011 and 2020. We used a case-crossover model with a binomial likelihood distribution combined with a distributed lag non-linear model to capture the delayed and non-linear trends over a 21-day lag period to identify the optimal temperature range for Puducherry. The results are expressed as the fraction of CVD mortalities attributable to heat and cold, defined relative to the optimal temperature. We also performed stratified analyses to explore the associations between Tapp and age-and-sex, grouped and considered together, and different types of CVDs. Sensitivity analyses were performed, including using a quasi-Poisson time-series approach. RESULTS: We found that the optimal temperature range for Puducherry is between 30°C and 36°C with respect to CVDs. Both cold and hot non-optimal Tapp were associated with an increased risk of overall in-hospital CVD mortalities, resulting in a U-shaped association curve. Cumulatively, up to 17% of the CVD deaths could be attributable to non-optimal temperatures, with a slightly higher burden attributable to heat (9.1%) than cold (8.3%). We also found that males were more vulnerable to colder temperature; females above 60 years were more vulnerable to heat while females below 60 years were affected by both heat and cold. Mortality with cerebrovascular accidents was associated more with heat compared to cold, while ischemic heart diseases did not seem to be affected by temperature. CONCLUSION: Both heat and cold contribute to the burden of CVDs attributable to non-optimal temperatures in the tropical Puducherry. Our study also identified the age-and-sex and CVD type differences in temperature attributable CVD mortalities. Further studies from India could identify regional associations, inform our understanding of the health implications of climate change in India and enhance the development of regional and contextual climate-health action-plans.

Ambient Particulate Air Pollution and Daily Mortality in 652 Cities.

BACKGROUND: The systematic evaluation of the results of time-series studies of air pollution is challenged by differences in model specification and publication bias. METHODS: We evaluated the associations of inhalable particulate matter (PM) with an aerodynamic diameter of 10 µm or less (PM10) and fine PM with an aerodynamic diameter of 2.5 µm or less (PM2.5) with daily all-cause, cardiovascular, and respiratory mortality across multiple countries or regions. Daily data on mortality and air pollution were collected from 652 cities in 24 countries or regions. We used overdispersed generalized additive models with random-effects meta-analysis to investigate the associations. Two-pollutant models were fitted to test the robustness of the associations. Concentration-response curves from each city were pooled to allow global estimates to be derived. RESULTS: On average, an increase of 10 µg per cubic meter in the 2-day moving average of PM10 concentration, which represents the average over the current and previous day, was associated with increases of 0.44% (95% confidence interval [CI], 0.39 to 0.50) in daily all-cause mortality, 0.36% (95% CI, 0.30 to 0.43) in daily cardiovascular mortality, and 0.47% (95% CI, 0.35 to 0.58) in daily respiratory mortality. The corresponding increases in daily mortality for the same change in PM2.5 concentration were 0.68% (95% CI, 0.59 to 0.77), 0.55% (95% CI, 0.45 to 0.66), and 0.74% (95% CI, 0.53 to 0.95). These associations remained significant after adjustment for gaseous pollutants. Associations were stronger in locations with lower annual mean PM concentrations and higher annual mean temperatures. The pooled concentration-response curves showed a consistent increase in daily mortality with increasing PM concentration, with steeper slopes at lower PM concentrations. CONCLUSIONS: Our data show independent associations between short-term exposure to PM10 and PM2.5 and daily all-cause, cardiovascular, and respiratory mortality in more than 600 cities across the globe. These data reinforce the evidence of a link between mortality and PM concentration established in regional and local studies. (Funded by the National Natural Science Foundation of China and others.).

Ambient heat exposure and COPD hospitalisations in England: a nationwide case-crossover study during 2007-2018.

BACKGROUND: There is emerging evidence suggesting a link between ambient heat exposure and chronic obstructive pulmonary disease (COPD) hospitalisations. Individual and contextual characteristics can affect population vulnerabilities to COPD hospitalisation due to heat exposure. This study quantifies the effect of ambient heat on COPD hospitalisations and examines population vulnerabilities by age, sex and contextual characteristics. METHODS: Individual data on COPD hospitalisation at high geographical resolution (postcodes) during 2007-2018 in England was retrieved from the small area health statistics unit. Maximum temperature at 1 km ×1 km resolution was available from the UK Met Office. We employed a case-crossover study design and fitted Bayesian conditional Poisson regression models. We adjusted for relative humidity and national holidays, and examined effect modification by age, sex, green space, average temperature, deprivation and urbanicity. RESULTS: After accounting for confounding, we found 1.47% (95% Credible Interval (CrI) 1.19% to 1.73%) increase in the hospitalisation risk for every 1°C increase in temperatures above 23.2°C (lags 0-2 days). We reported weak evidence of an effect modification by sex and age. We found a strong spatial determinant of the COPD hospitalisation risk due to heat exposure, which was alleviated when we accounted for contextual characteristics. 1851 (95% CrI 1 576 to 2 079) COPD hospitalisations were associated with temperatures above 23.2°C annually. CONCLUSION: Our study suggests that resources should be allocated to support the public health systems, for instance, through developing or expanding heat-health alerts, to challenge the increasing future heat-related COPD hospitalisation burden.

Differential Mortality Risks Associated With PM2.5 Components: A Multi-Country, Multi-City Study.

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.

A tutorial on the case time series design for small-area analysis.

BACKGROUND: The increased availability of data on health outcomes and risk factors collected at fine geographical resolution is one of the main reasons for the rising popularity of epidemiological analyses conducted at small-area level. However, this rich data setting poses important methodological issues related to modelling complexities and computational demands, as well as the linkage and harmonisation of data collected at different geographical levels. METHODS: This tutorial illustrated the extension of the case time series design, originally proposed for individual-level analyses on short-term associations with time-varying exposures, for applications using data aggregated over small geographical areas. The case time series design embeds the longitudinal structure of time series data within the self-matched framework of case-only methods, offering a flexible and highly adaptable analytical tool. The methodology is well suited for modelling complex temporal relationships, and it provides an efficient computational scheme for large datasets including longitudinal measurements collected at a fine geographical level. RESULTS: The application of the case time series for small-area analyses is demonstrated using a real-data case study to assess the mortality risks associated with high temperature in the summers of 2006 and 2013 in London, UK. The example makes use of information on individual deaths, temperature, and socio-economic characteristics collected at different geographical levels. The tutorial describes the various steps of the analysis, namely the definition of the case time series structure and the linkage of the data, as well as the estimation of the risk associations and the assessment of vulnerability differences. R code and data are made available to fully reproduce the results and the graphical descriptions. CONCLUSIONS: The extension of the case time series for small-area analysis offers a valuable analytical tool that combines modelling flexibility and computational efficiency. The increasing availability of data collected at fine geographical scales provides opportunities for its application to address a wide range of epidemiological questions.

The Short-term Impact of Standardised Packaging on Smoking and Snus Use in Norway.

INTRODUCTION: Standardised packaging on tobacco products was required in Norway July 1, 2018. We report pre-registered analyses of the potential impact on daily smoking and on daily snus use among women and men. METHODS: Interrupted time series (segmented regression) on repeated cross-sectional surveys (2012-2019) from two sources: probability samples (Registry Sample, N = 46,957) and market research samples (Market Research Sample, N = 64,465) of Norwegian adults aged 16-79. Self-reported daily smoking and snus use were regressed on a step change impact variable, controlled for trend and demographics (sex, age, region, and education based on national registers in the Registry Sample, and self-reported in the Market Research Sample). RESULTS: There were tendencies of a decline in smoking (Odds Ratio [OR] = 0.94; 95% confidence interval [CI] = 0.87, 1.02; lower-tail p-value [Plower] = 0.07), and women's snus use (OR = 0.89; CI = 0.77, 1.03; Plower = 0.06), but not men's snus use (OR = 1.01; CI = 0.92, 1.11; Plower = 0.59). Analyses using only the Registry Sample did not detect declines in smoking (OR = 0.99; CI = 0.88, 1.11; Plower = 0.43) or women's snus use (OR = 0.99; CI = 0.80, 1.24]; Plower = 0.48), and indicated no decline in men's snus use (OR = 1.18; CI = 1.03, 1.35; Plower = 0.99). Exploratory analyses suggested potential acceleration of the declining trend in smoking (change in trends, OR = 0.97) and of the increasing trend in men's snus use (OR = 1.03). CONCLUSIONS: The analyses indicate that standardised packaging in Norway did not produce a decline in men's snus use. Results are inconclusive regarding smoking and women's snus use. Exploratory analyses indicated a decrease in smoking and an increase in men's snus use. IMPLICATIONS: We could not confirm or disconfirm whether standardised packaging is an effective tobacco control measure in a Norwegian context. According to our analyses, standardized packaging may have effects on smoking prevalence and women's snus use, but is unlikely to reduce men's snus use. The present results may reflect higher effectiveness of standardised packaging for products with stronger health warnings. As the results varied according to samples and outcomes, the study underlines the importance of pre-registering future analyses on this topic. Future confirmatory research should test models of gradual impact of standardised packaging.

Extended two-stage designs for environmental research.

BACKGROUND: The two-stage design has become a standard tool in environmental epidemiology to model multi-location data. However, its standard form is rather inflexible and poses important limitations for modelling complex risks associated with environmental factors. In this contribution, we illustrate multiple design extensions of the classical two-stage method, all implemented within a unified analytic framework. METHODS: We extended standard two-stage meta-analytic models along the lines of linear mixed-effects models, by allowing location-specific estimates to be pooled through flexible fixed and random-effects structures. This permits the analysis of associations characterised by combinations of multivariate outcomes, hierarchical geographical structures, repeated measures, and/or longitudinal settings. The analytic framework and inferential procedures are implemented in the R package mixmeta. RESULTS: The design extensions are illustrated in examples using multi-city time series data collected as part of the National Morbidity, Mortality and Air Pollution Study (NMMAPS). Specifically, four case studies demonstrate applications for modelling complex associations with air pollution and temperature, including non-linear exposure-response relationships, effects clustered at multiple geographical levels, differential risks by age, and effect modification by air conditioning in a longitudinal analysis. CONCLUSIONS: The definition of several design extensions of the classical two-stage design within a unified framework, along with its implementation in freely-available software, will provide researchers with a flexible tool to address novel research questions in two-stage analyses of environmental health risks.