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OBJECTIVE Ambient extreme temperatures have been associated with mental and behavior disorders (MBDs). However, few studies have assesed whether vulnerability factors such as ambient air pollution, pre-existing mental health conditions and residential environmental factors increase susceptibility. This study aims to evaluate the associations between short-term variations in outdoor ambient extreme temperatures and MBD-related emergency department (ED) visits and how these associations are modified by vulnerability factors. METHODS We conducted a case-crossover study of 9,958,759 MBD ED visits in Alberta and Ontario, Canada made between March 1st, 2004 and December 31st, 2020. Daily average temperature was assigned to individual cases with ED visits for MBD using gridded data at a 1 km × 1 km spatial resolution. Conditional logistic regression was used to estimate associations between extreme temperatures (i.e., risk of ED visit at the 2.5th percentile temperature for cold and 97.5th percentile temperature for heat for each health region compared to the minimal temperature risk) and MBD ED visits. Age, sex, pre-existing mental health conditions, ambient air pollution (i.e. PM2.5, NO2 and O3) and residential environmental factors (neighborhood deprivation, residential green space exposure and urbanization) were evaluated as potential effect modifiers. RESULTS Cumulative exposure to extreme heat over 0-5 days (odds ratio [OR] = 1.145; 95% CI: 1.121-1.171) was associated with ED visits for any MBD. However, cumulative exposure to extreme cold was associated with lower risk of ED visits for any MBD (OR = 0.981; 95% CI: 0.976-0.987). We also found heat to be associated with ED visits for specific MBDs such as substance use disorders, dementia, neurotic disorders, schizophrenia and personality behavior disorder. Individuals with pre-existing mental health conditions, those exposed to higher daily concentrations of NO2 and O3 and those residing in neighborhoods with greater material and social deprivation were at higher risk of heat-related MBD ED visits. Increasing tree canopy coverage appeared to mitigate risks of the effect of heat on MBD ED visits. CONCLUSIONS Findings provide evidence that the impacts of heat on MBD ED visits may vary across different vulnerability factors.

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. Clinical Perspective_ What Is New?: This study provided evidence from what we believe is the largest multinational dataset ever assembled on cardiovascular outcomes and environmental exposures; Extreme hot and cold temperatures were associated with increased risk of death from any cardiovascular cause, ischemic heart disease, stroke, and heart failure; For every 1000 cardiovascular deaths, 2 and 9 excess deaths were attributed to extreme hot and cold days, respectively. _ What Are the Clinical Implications?: Extreme temperatures from a warming planet may become emerging priorities for public health and preventative cardiology; The findings of this study should prompt professional cardiology societies to commission scientific statements on the intersections of extreme temperature exposure and cardiovascular health. This study was supported by the Kuwait Foundation for the Advancement of Science (CB21-63BO-01); the US Environmental Protection Agency (RD-835872); Harvard Chan National Institute of Environmental Health Sciences Center for Environmental Health (P01ES009825); the UK Medical Research Council (MR/R013349/1); the UK Natural Environment Research Council (NE/R009384/1); the European Union’s Horizon 2020 Project Exhaustion (820655); the Australian National Health and Medical Research Council (APP 2000581, APP 1109193, APP 1163693); the National Institute of Environmental Health Sciences–funded HERCULES Center (P30ES019776); the MCIN/AEI/10.13039/501100011033 (grant CEX2018-000794-S); the Taiwanese Ministry of Science and Technology (MOST 109–2621-M-002–021); the Environmental Restoration and Conservation Agency, Environment Research and Technology Development Fund (JPMEERF15S11412); the São Paulo Research Foundation; and Fundação para a Ciência e a Tecnlogia (SFRH/BPD/115112/2016) info:eu-repo/semantics/publishedVersion

Evidence on the potential interactive effects of heat and ambient air pollution on cause-specific mortality is inconclusive and limited to selected locations., Masna Rai, Massimo Stafoggia, Francesca K. de’ Donato, Sofia Zafeiratou, Liliana Vazquez Fernandez, Siqi Zhang, Klea Katsouyanni, Evangelia Samoli, Shilpa Rao, Antonio Gasparrini, Pierre Masselot, and Alexandra Schneider were supported by the European Union’s Horizon 2020 Project Exhaustion (Grant ID: 820655). Joana Madureira was supported by the Fundação para a Ciência e a Tecnologia (FCT) (Grant SFRH/BPD/115112/2016).

BackgroundPrevious studies have found an association between warm temperature and asthma hospitalisation. They have reported different sex- 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.MethodsWe retrieved individual-level data on summer asthma hospitalisation at high temporal (daily) and spatial (postcodes) resolution during 2002-2019 in England from the NHS Digital. Daily mean temperature at 1km x 1km resolution was retrieved from the UK Met Office. We focused on lags 0-3 days. We employed a case-cross over study design and fitted Bayesian hierarchal Poisson models accounting for possible confounders (rainfall, relative humidity, wind speed, national holidays, and recurrent hospitalisations).ResultsAfter accounting for confounding, we found a 0.85% (95% Credible Interval: 0.64% to 1.07%) increase in the asthma hospitalisation risk for every 1°C increase in the ambient summer temperature. The effect was highest for males aged 15-65 (2.44%, 1.99% to 2.90%). During 2002-2007 we observed a 2.23% (1.86% to 2.60%) increase in hospitalisation risk per 1°C increase in temperature, whereas inconclusive evidence for the periods 2008-2013 and 2014-2019. Populations in Yorkshire and the Humber and East Midlands were the most vulnerable.ConclusionThis study provides evidence of an association between warm temperature and hospital admission for asthma, which was attenuated over time suggesting adaptive mechanisms to heat exposure or differences in lifestyle, comorbid conditions, and occupation over time.

Heat- and cold-related mortality risks are highly variable across different geographies, suggesting a differential distribution of vulnerability factors between and within countries, which could partly be driven by urban-to-rural disparities. Identifying these drivers of risk is crucial to characterize local vulnerability and design tailored public health interventions to improve adaptation of populations to climate change. We aimed to assess how heat- and cold-mortality risks change across urban, peri-urban and rural areas in Switzerland and to identify and compare the factors associated with increased vulnerability within and between different area typologies. We estimated the heat- and cold-related mortality association using the case time-series design and distributed lag non-linear models over daily mean temperature and all-cause mortality series between 1990–2017 in each municipality in Switzerland. Then, through multivariate meta-regression, we derived pooled heat and cold-mortality associations by typology (i.e. urban/rural/peri-urban) and assessed potential vulnerability factors among a wealth of demographic, socioeconomic, topographic, climatic, land use and other environmental data. Urban clusters reported larger pooled heat-related mortality risk (at 99th percentile, vs. temperature of minimum mortality (MMT)) (relative risk = 1.17 (95%CI: 1.10; 1.24), vs peri-urban 1.03 (1.00; 1.06), and rural 1.03 (0.99; 1.08)), but similar cold-mortality risk (at 1st percentile, vs. MMT) (1.35 (1.28; 1.43), vs rural 1.28 (1.14; 1.44) and peri-urban 1.39 (1.27–1.53)) clusters. We found different sets of vulnerability factors explaining the differential risk patterns across typologies. In urban clusters, mainly environmental factors (i.e. PM2.5) drove differences in heat-mortality association, while for peri-urban/rural clusters socio-economic variables were also important. For cold, socio-economic variables drove changes in vulnerability across all typologies, while environmental factors and ageing were other important drivers of larger vulnerability in peri-urban/rural clusters, with heterogeneity in the direction of the association. Our findings suggest that urban populations in Switzerland may be more vulnerable to heat, compared to rural locations, and different sets of vulnerability factors may drive these associations in each typology. Thus, future public health adaptation strategies should consider local and more tailored interventions rather than a one-size fits all approach.

The authors would like to acknowledge the participation of 4 additional authors to this article. They contributed to the processing of the Japanese dataset used in the study. The corrected authorship, the corrected Acknowledgements and the corrected Contributors and Declaration of interests sections are presented below. H.M.C. and W.L. performed data analysis. W.L., D.R., A.U., A.E., A.M.V., A.Z., A.G., A.Z., A.T., B.A., B.F., C.Í., C.Å., C.F.S.N., E.I., E.L., F.M., F.A., F.S., H.O. H.K., J.K., J.M., J.S., J.J., K.K., M.H.D., M.S.R., M.H., M.P., N.R., N.S., S.O., S.T., X.S., Y.H., Y.K., YL.G., Y.G., and M.L.B. provided essential data resources. H.M.C. drafted the first version. H.M.C. and M.L.B. performed writing and editing the manuscript. H.M.C., W.L., A.U., A.G., A.T., B.A., E.L., F.S., S.T., and M.L.B. conducted reviewing. H.M.C. and D.R. have developed the figures. All authors have read and acknowledged the final manuscript., This publication was developed under Assistance Agreement No. RD83587101 awarded by the U.S. Environmental Protection Agency to Yale University. It has not been formally reviewed by EPA. The views expressed in this document are solely those of the authors and do not necessarily reflect those of the Agency. EPA does not endorse any products or commercial services mentioned in this publication. Research reported in this publication was also supported by the National Institute on Minority Health and Health Disparities of the National Institutes of Health under Award Number R01MD012769. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Also, this work has been supported by the National Research Foundation of Korea (2021R1A6A3A03038675), Medical Research Council-UK (MR/V034162/1 and MR/R013349/1), Natural Environment Research Council UK (Grant ID: NE/R009384/1), Academy of Finland (Grant ID: 310372), European Union’s Horizon 2020 Project Exhaustion (Grant ID: 820655 and 874990), Czech Science Foundation (22-24920S), Emory University’s NIEHS-funded HERCULES Center (Grant ID: P30ES019776), and Grant CEX2018-000794-S funded by MCIN/AEI/10.13039/501100011033. The funders had no role in the design, data collection, analysis, interpretation of results, manuscript writing, or decision to publication.

BACKGROUND Epidemiological literature on the health risks associated with non-optimal temperature has mostly reported average estimates across large areas or specific population groups. However, the heterogeneous distribution of drivers of vulnerability can result in local differences in health risks associated with heat and cold. We aimed to analyse the association between ambient air temperature and all-cause mortality across England and Wales and characterise small scale patterns in temperature-related mortality risks and impacts. METHODS We performed a country-wide small-area analysis using data on all-cause mortality and air temperature for 34 753 lower super output areas (LSOAs) within 348 local authority districts (LADs) across England and Wales between Jan 1, 2000, and Dec 31, 2019. We first performed a case time series analysis of LSOA-specific and age-specific mortality series matched with 1 × 1 km gridded temperature data using distributed lag non-linear models, and then a repeated-measure multivariate meta-regression to pool LAD-specific estimates using area-level climatological, socioeconomic, and topographical predictors. FINDINGS The final analysis included 10 716 879 deaths from all causes. The small-area assessment estimated that each year in England and Wales, there was on average 791 excess deaths (empirical 95% CI 611-957) attributable to heat and 60 573 (55 796-65 145) attributable to cold, corresponding to standardised excess mortality rates of 1·57 deaths (empirical 95% CI 1·21-1·90) per 100 000 person-years for heat and 122·34 deaths (112·90-131·52) per 100 000 person-years for cold. The risks increased with age and were highly heterogeneous geographically, with the minimum mortality temperature ranging from 14·9°C to 22·6°C. Heat-related mortality was higher in urban areas, whereas cold-related mortality showed a more nuanced geographical pattern and increased risk in areas with greater socioeconomic deprivation. INTERPRETATION This study provides a comprehensive assessment of excess mortality related to non-optimal outdoor temperature, with several risk indicators reported by age and multiple geographical levels. The analysis provides detailed risk maps that are useful for designing effective public health and climate policies at both local and national levels. FUNDING Medical Research Council, Natural Environment Research Council, EU Horizon 2020 Programme, National Institute of Health Research.

Studies have shown that larger temperature-related health impacts may be associated with cold rather than with hot temperatures. Although it remains unclear the cold-related health burden in warmer regions, in particular at the national level in Brazil. We address this gap by examining the association between low ambient temperature and daily hospital admissions for cardiovascular and respiratory diseases in Brazil between 2008 and 2018. We first applied a case time series design in combination with distributed lag non-linear modeling (DLNM) framework to assess the association of low ambient temperature with daily hospital admissions by Brazilian region. Here, we also stratified the analyses by sex, age group (15-45, 46-65, and >65 years), and cause (respiratory and cardiovascular hospital admissions). In the second stage, we performed a meta-analysis to estimate pooled effects across the Brazilian regions. Our sample included more than 23 million hospitalizations for cardiovascular and respiratory diseases nationwide between 2008 and 2018, of which 53% were admissions for respiratory diseases and 47% for cardiovascular diseases. Our findings suggest that low temperatures are associated with a relative risk of 1.17 (95% CI: 1.07; 1.27) and 1.07 (95% CI: 1.01; 1.14) for cardiovascular and respiratory admissions in Brazil, respectively. The pooled national results indicate robust positive associations for cardiovascular and respiratory hospital admissions in most of the subgroup analyses. In particular, for cardiovascular hospital admissions, men and older adults (>65 years old) were slightly more impacted by cold exposure. For respiratory admissions, the results did not indicate differences among the population groups by sex and age. This study can help decision-makers to create adaptive measures to protect public health from the effects of cold temperature.

BackgroundThere 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.MethodsIndividual 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×1km resolution was available from the UK Met Office. We employed a case-cross over 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.ResultsAfter accounting for confounding, we found a 1.47% (95% Credible Interval 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, that was alleviated when we accounted for contextual characteristics. 1 851 (95% CrI 1 576 to 2 079) COPD hospitalisations were associated with temperatures above 23.2°C annually.ConclusionOur 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.Key MessagesWhat is the key question?What is the short-term effect of heat exposure on COPD hospitalisation and which contextual/societal factors affect population vulnerability?What is the bottom line?For every 1°C increase in summer temperatures higher than 23.2°C, the risk of COPD hospitalisation increases by 1.47%, and populations in the North and in the South East are more vulnerable.Why read on?This large nationwide study in England using individual data quantifies the effect of heat exposure on COPD hospitalisations; these findings inform future policies regarding preparedness and resilience of public health systems against the increasing COPD burden due to the increasing temperatures.

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.

AIM OF THE STUDY: Previous literature suggests that ambient temperature may play a role in increasing the risk of suicide. Although in Switzerland suicides are an important cause of death, limited research exists on risk factors for suicidal behaviour, including ambient temperature. We aimed to assess the short-term association between ambient temperature and suicide risk in Switzerland between 1995 and 2016, and the differences by region, individual characteristics and method of suicide. METHODS: We collected daily data on suicides and mean temperatures in each canton of Switzerland. We used a two-stage approach, consisting of a case time series analysis using conditional quasi-Poisson and distributed lag non-linear models followed by a multivariate meta-regression analysis. We conducted subgroup analyses by sex, age (65 years) and method of suicide (violent or nonviolent). RESULTS: Between 1995 and 2016, there were a total of 24,067 suicides in Switzerland. Overall, we found a positive and non-linear temperature–suicide association in all regions. On average, the risk of suicide increased by 34% (1.34 relative risk [95% confidence interval: 1.19–1.52]) from the 10th to the 99th temperature percentile in Switzerland (lag period of 0–2 days). Indications of larger risks were mostly found in females, younger individuals (

Studies have investigated the effects of heat and temperature variability (TV) on mortality. However, few assessed whether TV modifies the heat-mortality association. Data on daily temperature and mortality in the warm season were collected from 717 locations across 36 countries. TV was calculated as the standard deviation of the average of the same and previous days' minimum and maximum temperatures. We used location-specific quasi-Poisson regression models with an interaction term between the cross-basis term for mean temperature and quartiles of TV to obtain heat-mortality associations under each quartile of TV, and then pooled estimates at the country, regional, and global levels. Results show the increased risk in heat-related mortality with increments in TV, accounting for 0.70% (95% confidence interval [CI]: -0.33 to 1.69), 1.34% (95% CI: -0.14 to 2.73), 1.99% (95% CI: 0.29-3.57), and 2.73% (95% CI: 0.76-4.50) of total deaths for Q1-Q4 (first quartile-fourth quartile) of TV. The modification effects of TV varied geographically. Central Europe had the highest attributable fractions (AFs), corresponding to 7.68% (95% CI: 5.25-9.89) of total deaths for Q4 of TV, while the lowest AFs were observed in North America, with the values for Q4 of 1.74% (95% CI: -0.09 to 3.39). TV had a significant modification effect on the heat-mortality association, causing a higher heat-related mortality burden with increments of TV. Implementing targeted strategies against heat exposure and fluctuant temperatures simultaneously would benefit public health., This study was supported by the Australian Research Council (DP210102076) and the Australian National Health and Medical Research Council (APP2000581). Y.W and B.W. were supported by the China Scholarship Council (nos. 202006010044 and 202006010043); S.L. was supported by an Emerging Leader Fellowship of the Australian National Health and Medical Research Council (no. APP2009866); Y.G. was supported by Career Development Fellowship (no. APP1163693) and Leader Fellowship (no. APP2008813) of the Australian National Health and Medical Research Council; J.K. and A.U. were supported by the Czech Science Foundation (project no. 20–28560S); N.S. was supported by the National Institute of Environmental Health Sciences-funded HERCULES Center (no. P30ES019776); Y.H. was supported by the Environment Research and Technology Development Fund (JPMEERF15S11412) of the Environmental Restoration and Conservation Agency; M.d.S.Z.S.C. and P.H.N.S. were supported by the São Paulo Research Foundation (FAPESP); H.O. and E.I. were supported by the Estonian Ministry of Education and Research (IUT34–17); J.M. was supported by a fellowship of Fundação para a Ciência e a Tecnlogia (SFRH/BPD/115112/2016); A.G. and F.S. were supported by the Medical Research Council UK (grant ID MR/R013349/1), the Natural Environment Research Council UK (grant ID NE/R009384/1), and the EU’s Horizon 2020 project, Exhaustion (grant ID 820655); A.S. and F.d.D. were supported by the EU’s Horizon 2020 project, Exhaustion (grant ID 820655); V.H. was supported by the Spanish Ministry of Economy, Industry and Competitiveness (grant ID PCIN-2017–046); and A.T. by MCIN/AEI/10.13039/501100011033 (grant CEX2018-000794-S). Statistics South Africa kindly provided the mortality data, but had no other role in the study.

Identifying how greenspace impacts the temperature-mortality relationship in urban environments is crucial, especially given climate change and rapid urbanization. However, the effect modification of greenspace on heat-related mortality has been typically focused on a localized area or single country. This study examined the heat-mortality relationship among different greenspace levels in a global setting., This publication was developed under Assistance Agreement No. RD83587101 awarded by the U.S. Environmental Protection Agency to Yale University. It has not been formally reviewed by EPA. The views expressed in this document are solely those of the authors and do not necessarily reflect those of the Agency. EPA does not endorse any products or commercial services mentioned in this publication. Research reported in this publication was also supported by the National Institute on Minority Health and Health Disparities of the National Institutes of Health under Award Number R01MD012769. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Also, this work has been supported by the National Research Foundation of Korea (2021R1A6A3A03038675), Medical Research CouncilUK (MR/V034162/1 and MR/R013349/1), Natural Environment Research Council UK (Grant ID: NE/ R009384/1), Academy of Finland (Grant ID: 310372), European Union’s Horizon 2020 Project Exhaustion (Grant ID: 820655 and 874990), Czech Science Foundation (22-24920S), Emory University’s NIEHS-funded HERCULES Center (Grant ID: P30ES019776), and Grant CEX2018-000794-S funded by MCIN/AEI/ 10.13039/501100011033 The funders had no role in the design, data collection, analysis, interpretation of results, manuscript writing, or decision to publication.

Background: Increased mortality risk is associated with short-term temperature variability. However, to our knowledge, there has been no comprehensive assessment of the temperature variability-related mortality burden worldwide. In this study, using data from the MCC Collaborative Research Network, we first explored the association between temperature variability and mortality across 43 countries or regions. Then, to provide a more comprehensive picture of the global burden of mortality associated with temperature variability, global gridded temperature data with a resolution of 0·5° × 0·5° were used to assess the temperature variability-related mortality burden at the global, regional, and national levels. Furthermore, temporal trends in temperature variability-related mortality burden were also explored from 2000–19. Methods: In this modelling study, we applied a three-stage meta-analytical approach to assess the global temperature variability-related mortality burden at a spatial resolution of 0·5° × 0·5° from 2000–19. Temperature variability was calculated as the SD of the average of the same and previous days’ minimum and maximum temperatures. We first obtained location-specific temperature variability related-mortality associations based on a daily time series of 750 locations from the Multi-country Multi-city Collaborative Research Network. We subsequently constructed a multivariable meta-regression model with five predictors to estimate grid-specific temperature variability related-mortality associations across the globe. Finally, percentage excess in mortality and excess mortality rate were calculated to quantify the temperature variability-related mortality burden and to further explore its temporal trend over two decades. Findings: An increasing trend in temperature variability was identified at the global level from 2000 to 2019. Globally, 1 753 392 deaths (95% CI 1 159 901–2 357 718) were associated with temperature variability per year, accounting for 3·4% (2·2–4·6) of all deaths. Most of Asia, Australia, and New Zealand were observed to have a higher percentage excess in mortality than the global mean. Globally, the percentage excess in mortality increased by about 4·6% (3·7–5·3) per decade. The largest increase occurred in Australia and New Zealand (7·3%, 95% CI 4·3–10·4), followed by Europe (4·4%, 2·2–5·6) and Africa (3·3, 1·9–4·6). Interpretation: Globally, a substantial mortality burden was associated with temperature variability, showing geographical heterogeneity and a slightly increasing temporal trend. Our findings could assist in raising public awareness and improving the understanding of the health impacts of temperature variability. Funding: Australian Research Council, Australian National Health & Medical Research Council., This study was supported by the Australian Research Council (DP210102076) and the Australian National Health and Medical Research Council (APP2000581). YW was supported by the China Scholarship Council (number 202006010044). SL was supported by an Emerging Leader Fellowship of the Australian National Health and Medical Research Council (number APP2009866). QZ was supported by the Program of Qilu Young Scholars of Shandong University, Jinan, China. BW was supported by the China Scholarship Council (number 202006010043). JK and AU were supported by the Czech Science Foundation (project number 20–28560S). NS was supported by the National Institute of Environmental Health Sciences-funded HERCULES Center (P30ES019776). S-CP and YLG were supported by the Ministry of Science and Technology (Taiwan; MOST 109–2621-M-002–021). YH was supported by the Environment Research and Technology Development Fund (JPMEERF15S11412) of the Environmental Restoration and Conservation Agency. MdSZSC and PHNS were supported by the São Paulo Research Foundation (FAPESP). ST was supported by the Science and Technology Commission of Shanghai Municipality (grant number 18411951600). HO and EI were supported by the Estonian Ministry of Education and Research (IUT34–17). JM was supported by a fellowship of Fundação para a Ciência e a Tecnlogia (SFRH/BPD/115112/2016). AG and FS were supported by the Medical Research Council UK (grant ID MR/R013349/1), the Natural Environment Research Council UK (grant ID NE/R009384/1), and the EU's Horizon 2020 project, Exhaustion (grant ID 820655). AS, SR, and FdD were supported by the EU's Horizon 2020 project, Exhaustion (grant ID 820655). VH was supported by the Spanish Ministry of Economy, Industry and Competitiveness (grant ID PCIN-2017–046). AT was supported by MCIN/AEI/10.13039/501100011033 (grant CEX2018-000794-S). YG was supported by the Career Development Fellowship (number APP1163693) and Leader Fellowship (number APP2008813) of the Australian National Health and Medical Research Council. Statistics South Africa kindly provided the mortality data, but had no other role in the study. This Article is published in memory of Simona Fratianni, who helped to contribute the data for Romania.