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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

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.

There is substantial epidemiological evidence on the associations between cold weather and adverse health effects. Meteorological alarm systems are being developed globally, and generalized protective advice is given to the public based on outdoor exposure parameters. It is not clear how these shared outdoor exposure parameters relate to the individual-level thermal exposure indoors, where the majority of time is spent. We hypothesized a priori that there are opposite correlations between indoor and outdoor temperatures in residential apartments. Apartments were classified into 3 categories according to their response to declining outdoor temperature: under-controlled apartments cool down, controlled apartments maintain constant indoor temperature level, and over-controlled apartments warm up. Outdoor and indoor temperatures were measured in 30-min intervals in 417 residential apartments in 14 buildings in Kotka, Finland, between February and April 2018 with outdoor temperatures ranging from − 20.4 °C to + 14.0 °C. Different apartment types were present in all buildings. Floor and orientation did not explain the divergence. Indoor temperatures below the limit value + 20 °C by building code occurred in 26.2%, 7.9%, and 23.6% of the under-controlled, controlled, and over-controlled apartments, some in conjunction with increasing outdoor temperatures. Indoor temperatures above the limit + 25 °C occurred but were more rare. This proof-of-concept study demonstrates that while the home environment may be a source of thermal stress during cold weather, generalized advice for adjusting the heating may lead to paradoxical exposures in some cases. More elaborate conceptualizations of everyday thermal exposures are needed to safely reduce weather-related health risks using shared meteorological alarm systems. Electronic supplementary material The online version of this article (10.1007/s00484-020-01998-7) contains supplementary material, which is available to authorized users.

We conducted a time-series analysis of the relations between daily levels of allergenic pollen and mortality in the Helsinki Metropolitan Area with 153 378 deaths; 9742 from respiratory and 57 402 from cardiovascular causes. Daily (average) pollen counts of alder, birch, mugwort and grass were measured. In quasi-Poisson regression analysis, abundant alder pollen increased the risk of non-accidental deaths with an adjusted cumulative mortality rate ratio (acMRR) of 1.10 (95% CI 1.01–1.19) and of deaths from respiratory-diseases with acMRR of 1.78 (95% CI 1.19–2.65). Abundant mugwort pollen increased cardiovascular mortality (1.41, 1.02–1.95). These findings identify an important global public health problem.

Minimum mortality temperature (MMT) is an important indicator to assess the temperature-mortality association, indicating long-term adaptation to local climate. Limited evidence about the geographical variability of the MMT is available at a global scale.

Climate change affects human health; however, there have been no large-scale, systematic efforts to quantify the heat-related human health impacts that have already occurred due to climate change. Here, we use empirical data from 732 locations in 43 countries to estimate the mortality burdens associated with the additional heat exposure that has resulted from recent human-induced warming, during the period 1991–2018. Across all study countries, we find that 37.0% (range 20.5–76.3%) of warm-season heat-related deaths can be attributed to anthropogenic climate change and that increased mortality is evident on every continent. Burdens varied geographically but were of the order of dozens to hundreds of deaths per year in many locations. Our findings support the urgent need for more ambitious mitigation and adaptation strategies to minimize the public health impacts of climate change., We thank the participants of the ISIMIP Health workshop in Barcelona in November 2018 where this work was discussed for the first time. This study was supported by the Medical Research Council UK (grant no. MR/M022625/1), the Natural Environment Research Council UK (grant no. NE/R009384/1) and the European Union’s Horizon 2020 Project Exhaustion (grant no. 820655). N.S. was supported by the NIEHS-funded HERCULES Center (P30ES019776). Y.H. was supported by the Environment Research and Technology Development Fund of the Environmental Restoration and Conservation Agency, Japan (JPMEERF15S11412). J.J.J.K.J. was supported by Academy of Finland (grant no. 310372). V.H. was supported by the Spanish Ministry of Economy, Industry and Competitiveness (grant no. PCIN-2017-046) and the German Federal Ministry of Education and Research (grant no. 01LS1201A2). J.K. and A.U. were supported by the Czech Science Foundation (grant no. 20-28560S). J.M. was supported by the Fundação para a Ciência e a Tecnologia (FCT) (SFRH/BPD/115112/2016). S.R. and F.d.R. were supported by European Union’s Horizon 2020 Project EXHAUSTION (grant no. 820655). M.H. was supported by the Japan Science and Technology Agency as part of SICORP, grant no. JPMJSC20E4. Y.G. was supported by the Career Development Fellowship of the Australian National Health and Medical Research Council (APP1163693). S.L. was support by the Early Career Fellowship of the Australian National Health and Medical Research Council (APP1109193). Y.L.L.G. was supported by the Taiwan Ministry of Science and Technology (MOST110-2918-I-002-007) as a visiting academic at the University of Sydney.

Background: Exposure to cold or hot temperatures is associated with premature deaths. We aimed to evaluate the global, regional, and national mortality burden associated with non-optimal ambient temperatures. Methods: In this modelling study, we collected time-series data on mortality and ambient temperatures from 750 locations in 43 countries and five meta-predictors at a grid size of 0·5° × 0·5° across the globe. A three-stage analysis strategy was used. First, the temperature–mortality association was fitted for each location by use of a time-series regression. Second, a multivariate meta-regression model was built between location-specific estimates and meta-predictors. Finally, the grid-specific temperature–mortality association between 2000 and 2019 was predicted by use of the fitted meta-regression and the grid-specific meta-predictors. Excess deaths due to non-optimal temperatures, the ratio between annual excess deaths and all deaths of a year (the excess death ratio), and the death rate per 100 000 residents were then calculated for each grid across the world. Grids were divided according to regional groupings of the UN Statistics Division. Findings: Globally, 5 083 173 deaths (95% empirical CI [eCI] 4 087 967–5 965 520) were associated with non-optimal temperatures per year, accounting for 9·43% (95% eCI 7·58–11·07) of all deaths (8·52% [6·19–10·47] were cold-related and 0·91% [0·56–1·36] were heat-related). There were 74 temperature-related excess deaths per 100 000 residents (95% eCI 60–87). The mortality burden varied geographically. Of all excess deaths, 2 617 322 (51·49%) occurred in Asia. Eastern Europe had the highest heat-related excess death rate and Sub-Saharan Africa had the highest cold-related excess death rate. From 2000–03 to 2016–19, the global cold-related excess death ratio changed by −0·51 percentage points (95% eCI −0·61 to −0·42) and the global heat-related excess death ratio increased by 0·21 percentage points (0·13–0·31), leading to a net reduction in the overall ratio. The largest decline in overall excess death ratio occurred in South-eastern Asia, whereas excess death ratio fluctuated in Southern Asia and Europe. Interpretation: Non-optimal temperatures are associated with a substantial mortality burden, which varies spatiotemporally. Our findings will benefit international, national, and local communities in developing preparedness and prevention strategies to reduce weather-related impacts immediately and under climate change scenarios. Funding: Australian Research Council and the Australian National Health and Medical Research Council.

Objective To evaluate the short term associations between nitrogen dioxide (NO2) and total, cardiovascular, and respiratory mortality across multiple countries/regions worldwide, using a uniform analytical protocol. Design Two stage, time series approach, with overdispersed generalised linear models and multilevel meta-analysis. Setting 398 cities in 22 low to high income countries/regions. Main outcome measures Daily deaths from total (62.8 million), cardiovascular (19.7 million), and respiratory (5.5 million) causes between 1973 and 2018. Results On average, a 10 μg/m3 increase in NO2 concentration on lag 1 day (previous day) was associated with 0.46% (95% confidence interval 0.36% to 0.57%), 0.37% (0.22% to 0.51%), and 0.47% (0.21% to 0.72%) increases in total, cardiovascular, and respiratory mortality, respectively. These associations remained robust after adjusting for co-pollutants (particulate matter with aerodynamic diameter ≤10 μm or ≤2.5 μm (PM10 and PM2.5, respectively), ozone, sulfur dioxide, and carbon monoxide). The pooled concentration-response curves for all three causes were almost linear without discernible thresholds. The proportion of deaths attributable to NO2 concentration above the counterfactual zero level was 1.23% (95% confidence interval 0.96% to 1.51%) across the 398 cities. Conclusions This multilocation study provides key evidence on the independent and linear associations between short term exposure to NO2 and increased risk of total, cardiovascular, and respiratory mortality, suggesting that health benefits would be achieved by tightening the guidelines and regulatory limits of NO2., HaK was supported by the National Natural Science Foundation of China (92043301, 82030103, and 91843302) and China Medical Board Collaborating Program (16-250). AG and FS were supported by the Medical Research Council, UK (MR/M022625/1), the Natural Environment Research Council, UK (NE/R009384/1), and the European Union’s Horizon 2020 Project Exhaustion (820655). VH was supported by the Spanish Ministry of Science and Innovation (PCIN-2017-046), and the German Federal Ministry of Education and Research (01LS1201A2). YH and MH were supported by the Environment Research and Technology Development Fund (JPMEERF15S11412) of the Environmental Restoration and Conservation Agency, Japan. JK and AU were supported by the Czech Science Foundation (18-22125S). ST was supported by the Shanghai Municipal Science and Technology Commission (18411951600). Y-LLG was supported by a Career Development Fellowship of the Australian National Health and Medical Research Council (APP1163693). SL was supported by an Early Career Fellowship of the Australian National Health and Medical Research Council (APP1109193). JJKJJ and NR were supported by the Academy of Finland (310372). The funders had no role in considering the study design or in the collection, analysis, interpretation of data, writing of the report, or decision to submit the article for publication.

Summary Background Many regions of the world are now facing more frequent and unprecedentedly large wildfires. However, the association between wildfire-related PM2·5 and mortality has not been well characterised. We aimed to comprehensively assess the association between short-term exposure to wildfire-related PM2·5 and mortality across various regions of the world. Methods For this time series study, data on daily counts of deaths for all causes, cardiovascular causes, and respiratory causes were collected from 749 cities in 43 countries and regions during 2000–16. Daily concentrations of wildfire-related PM2·5 were estimated using the three-dimensional chemical transport model GEOS-Chem at a 0·25° × 0·25° resolution. The association between wildfire-related PM2·5 exposure and mortality was examined using a quasi-Poisson time series model in each city considering both the current-day and lag effects, and the effect estimates were then pooled using a random-effects meta-analysis. Based on these pooled effect estimates, the population attributable fraction and relative risk (RR) of annual mortality due to acute wildfire-related PM2·5 exposure was calculated. Findings 65·6 million all-cause deaths, 15·1 million cardiovascular deaths, and 6·8 million respiratory deaths were included in our analyses. The pooled RRs of mortality associated with each 10 μg/m3 increase in the 3-day moving average (lag 0–2 days) of wildfire-related PM2·5 exposure were 1·019 (95% CI 1·016–1·022) for all-cause mortality, 1·017 (1·012–1·021) for cardiovascular mortality, and 1·019 (1·013–1·025) for respiratory mortality. Overall, 0·62% (95% CI 0·48–0·75) of all-cause deaths, 0·55% (0·43–0·67) of cardiovascular deaths, and 0·64% (0·50–0·78) of respiratory deaths were annually attributable to the acute impacts of wildfire-related PM2·5 exposure during the study period., Australian Research Council, Australian National Health & Medical Research Council.

Background Epidemiological evidence on short-term association between ambient carbon monoxide (CO) and mortality is inconclusive and limited to single cities, regions, or countries. Generalisation of results from previous studies is hindered by potential publication bias and different modelling approaches. We therefore assessed the association between short-term exposure to ambient CO and daily mortality in a multicity, multicountry setting. Methods We collected daily data on air pollution, meteorology, and total mortality from 337 cities in 18 countries or regions, covering various periods from 1979 to 2016. All included cities had at least 2 years of both CO and mortality data. We estimated city-specific associations using confounder-adjusted generalised additive models with a quasi-Poisson distribution, and then pooled the estimates, accounting for their statistical uncertainty, using a random-effects multilevel meta-analytical model. We also assessed the overall shape of the exposure–response curve and evaluated the possibility of a threshold below which health is not affected. Findings Overall, a 1 mg/m3 increase in the average CO concentration of the previous day was associated with a 0·91% (95% CI 0·32–1·50) increase in daily total mortality. The pooled exposure–response curve showed a continuously elevated mortality risk with increasing CO concentrations, suggesting no threshold. The exposure–response curve was steeper at daily CO levels lower than 1 mg/m3, indicating greater risk of mortality per increment in CO exposure, and persisted at daily concentrations as low as 0·6 mg/m3 or less. The association remained similar after adjustment for ozone but was attenuated after adjustment for particulate matter or sulphur dioxide, or even reduced to null after adjustment for nitrogen dioxide. Interpretation This international study is by far the largest epidemiological investigation on short-term CO-related mortality. We found significant associations between ambient CO and daily mortality, even at levels well below current air quality guidelines. Further studies are warranted to disentangle its independent effect from other traffic-related pollutants., EU Horizon 2020, UK Medical Research Council, and Natural Environment Research Council

Air temperature has been the most commonly used exposure metric in assessing relationships between thermal stress and mortality. Lack of the high-quality meteorological station data necessary to adequately characterize the thermal environment has been one of the main limitations for the use of more complex thermal indices. Global climate reanalyses may provide an ideal platform to overcome this limitation and define complex heat and cold stress conditions anywhere in the world. In this study, we explored the potential of the Universal Thermal Climate Index (UTCI) based on ERA5 – the latest global climate reanalysis from the European Centre for Medium-Range Weather Forecasts (ECMWF) – as a health-related tool. Employing a novel ERA5-based thermal comfort dataset ERA5-HEAT, we investigated the relationships between the UTCI and daily mortality data in 21 cities across 9 European countries. We used distributed lag nonlinear models to assess exposure-response relationships between mortality and thermal conditions in individual cities. We then employed meta-regression models to pool the results for each city into four groups according to climate zone. To evaluate the performance of ERA5-based UTCI, we compared its effects on mortality with those for the station-based UTCI data. In order to assess the additional effect of the UTCI, the performance of ERA5-and station-based air temperature (T) was evaluated. Whilst generally similar heat- and cold-effects were observed for the ERA5-and station-based data in most locations, the important role of wind in the UTCI appeared in the results. The largest difference between any two datasets was found in the Southern European group of cities, where the relative risk of mortality at the 1st percentile of daily mean temperature distribution (1.29 and 1.30 according to the ERA5 vs station data, respectively) considerably exceeded the one for the daily mean UTCI (1.19 vs 1.22). These differences were mainly due to the effect of wind in the cold tail of the UTCI distribution. The comparison of exposure-response relationships between ERA5-and station-based data shows that ERA5-based UTCI may be a useful tool for definition of life-threatening thermal conditions in locations where high-quality station data are not available., We would like to thank all the national data providers for supplying meteorological as well as health data (see more details in the Supplementary Material). The study was primarily supported by the Czech Science Foundation, project no. 18-22125S (AU and JK), the European Commission's HORIZON2020 ANYWHERE project (Enhancing Emergency Management and Response to Extreme Weather and Climate Events, Project ID 700099, CDN, HLC), and FATHUM (Forecasts for AnTicipatory HUManitarian action) part of the UKRI NERC/DFID SHEAR programme, grant number NE/P000525/1 (HLC). The following individual grants also supported this work: Medical Research Council-UK (Grant ID: MR/M022625/1), Natural Environment Research Council UK (Grant ID: NE/R009384/1), European Union's Horizon 2020 Project Exhaustion (Grant ID: 820655), Spanish Ministry of Economy, Industry and Competitiveness (Grant ID: PCIN-2017-046).

Summary Background Various retrospective studies have reported on the increase of mortality risk due to higher diurnal temperature range (DTR). This study projects the effect of DTR on future mortality across 445 communities in 20 countries and regions. Methods DTR-related mortality risk was estimated on the basis of the historical daily time-series of mortality and weather factors from Jan 1, 1985, to Dec 31, 2015, with data for 445 communities across 20 countries and regions, from the Multi-Country Multi-City Collaborative Research Network. We obtained daily projected temperature series associated with four climate change scenarios, using the four representative concentration pathways (RCPs) described by the Intergovernmental Panel on Climate Change, from the lowest to the highest emission scenarios (RCP 2.6, RCP 4.5, RCP 6.0, and RCP 8.5). Excess deaths attributable to the DTR during the current (1985–2015) and future (2020–99) periods were projected using daily DTR series under the four scenarios. Future excess deaths were calculated on the basis of assumptions that warmer long-term average temperatures affect or do not affect the DTR-related mortality risk. Findings The time-series analyses results showed that DTR was associated with excess mortality. Under the unmitigated climate change scenario (RCP 8.5), the future average DTR is projected to increase in most countries and regions (by −0·4 to 1·6°C), particularly in the USA, south-central Europe, Mexico, and South Africa. The excess deaths currently attributable to DTR were estimated to be 0·2–7·4%. Furthermore, the DTR-related mortality risk increased as the long-term average temperature increased; in the linear mixed model with the assumption of an interactive effect with long-term average temperature, we estimated 0·05% additional DTR mortality risk per 1°C increase in average temperature. Based on the interaction with long-term average temperature, the DTR-related excess deaths are projected to increase in all countries or regions by 1·4–10·3% in 2090–99. Interpretation This study suggests that globally, DTR-related excess mortality might increase under climate change, and this increasing pattern is likely to vary between countries and regions. Considering climatic changes, our findings could contribute to public health interventions aimed at reducing the impact of DTR on human health.

Background: Various retrospective studies report that a higher diurnal temperature range (DTR) increases mortality risk. This study projects the impact of DTR on future mortality across 445 communities in 20 countries. Methods: We first estimated the DTR-related mortality risk based on the historical daily time-series of mortality and of weather factors from 1985 to 2015. Next, we projected the excess deaths attributable to the DTR during the current (1985–2015) and future (2020–2099) periods using daily DTR series under four climate-change scenarios. We then calculated the future excess deaths based on two assumptions: warmer temperatures affect or do not affect the DTR-mortality risk. Findings: DTR was associated with excess mortality in our time-series analyses. Under the unmitigated scenario, the future average DTR is projected to increase in most countries (-0·4–1·6 °C), and the increasing pattern was more evident in the United States, south-central Europe, Mexico, and South Africa. The excess deaths currently attributable to DTR were estimated to be 0·2–7·4%. Furthermore, the DTR-related mortality risk increased with an increasing average temperature. Based on the positive interactive effect between DTR and temperature, the DTR-related excess deaths are projected to increase in all countries (1·4–10·3%) in 2090–2099. Interpretation: This study suggests that the DTR-related excess mortality may increase globally under climate change, and this increasing pattern may vary between countries. Our findings can contribute to both international and regional public health interventions to reduce the DTR impacts on health under climate change. Funding Statement: Ho Kim is supported by the Korea Ministry of Environment via the “Climate Change Correspondence Program” (2014001310007). Declaration of Interests: All authors report no financial relationships with commercial interests.

BACKGROUND Regular long-term physical exercise has favourable effects on endothelial function in patients with coronary artery disease (CAD). However, the effects of an acute exercise bout in the cold on endothelial function are not known. METHODS At first, the effects of moderate-intensity aerobic lower-body exercise were assessed in CAD patients (n = 16) in a neutral [+22°C] and cold [-15°C] environment. Secondly, responses to static and dynamic upper-body exercise in a neutral [+22°C] and cold [-15°C] environment were investigated in CAD patients (n = 15). All experiments were performed in a random order. Endothelial function was measured by flow-mediated dilation (FMD) of the brachial artery in response to reactive hyperaemia, before and after the exposures in a neutral environment. RESULTS No significant temperature*exercise*condition (pre-post) interaction was observed in FMD% when comparing rest versus aerobic exercise or static versus dynamic upper-body exercise. Relative reactive hyperaemia during FMD protocol, measured by changes in shear rate, was elevated after rest compared to aerobic exercise (p = .001) and after static compared to dynamic upper-body exercise (p

Background Previous studies have provided evidence that prenatal exposure to low-level air pollution increases the risk of preterm birth (PTB), but the findings of the effects of short-term exposure have been inconclusive. Moreover, there is little knowledge on potential synergistic effects of different combinations of air pollutants. Objectives To assess independent and joint effects of prenatal exposure to air pollutants during the week prior to the delivery on the risk of PTB. Methods The study population included 2568 members of the Espoo Cohort Study, living in the City of Espoo, Finland, born between 1984 and 1990. We assessed individual-level prenatal exposure to ambient air pollutants of interest based on maternal residential addresses, while taking into account their residential mobility. We used both regional-to-city-scale dispersion modelling and land-use regression–based method to estimates the pollutant concentrations. We contrasted the risk of PTB in the highest quartile (Q4) of exposure to the lower exposure quartiles (Q1-Q3) during the specific periods of pregnancy. We applied Poisson regression analysis to estimate the adjusted risk ratios (RRs) with their 95% confidence intervals (CI), adjusting for season of birth, maternal age, sex of the baby, family's socioeconomic status, maternal smoking, and exposure to environmental tobacco smoke during pregnancy, single parenthood, and exposure to other air pollutants (this in multi-pollutant models). Results The risk of PTB was related to exposures to PM2.5, PM10 and NO2 during the week prior to the delivery with adjusted RRs of 1.67 (95%CI: 1.14, 2.46), 1.60 (95% CI: 1.09, 2.34) and 1.65 (95% CI: 1.14, 2.37), from three-pollutant models respectively. There were no significant joint effects for these different air pollutants (during the week prior to the delivery). Conclusion Our results provide evidence that exposure to fairly low-level air pollution may trigger PTB, but synergistic effects of different pollutants are not likely.

An increase in the global health burden of temperature was projected for 459 locations in 28 countries worldwide under four representative concentration pathway scenarios until 2099. We determined that the amount of temperature increase for each 100 ppm increase in global CO2 concentrations is nearly constant, regardless of climate scenarios. The overall average temperature increase during 2010–2099 is largest in Canada (1.16 °C/100 ppm) and Finland (1.14 °C/100 ppm), while it is smallest in Ireland (0.62 °C/100 ppm) and Argentina (0.63 °C/100 ppm). In addition, for each 1 °C temperature increase, the amount of excess mortality is increased largely in tropical countries such as Vietnam (10.34%p/°C) and the Philippines (8.18%p/°C), while it is decreased in Ireland (−0.92%p/°C) and Australia (−0.32%p/°C). To understand the regional variability in temperature increase and mortality, we performed a regression-based modeling. We observed that the projected temperature increase is highly correlated with daily temperature range at the location and vulnerability to temperature increase is affected by health expenditure, and proportions of obese and elderly population. © 2019, This study was supported by the Global Research Lab (# K21004000001-10A0500-00710 ) through the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT (Information and Communication Technologies), and Future Planning. JL was supported by the National Research Foundation of Korea as NRF-SNSF Researcher Exchange Program ( NRF-2018K2A9A1A06086694 ). AG was supported by Medical Research Council UK (Grant ID: MR/M022625/1 ) and Natural Environment Research Council UK (Grant ID: NE/R009384/1 ). JK and AU were supported by the Czech Science Foundation , project no. 18-22125S . HO and EI were supported by the Estonian Ministry of Education and Research (Grant no IUT34-17 ). JJKJ and NRIR were supported by the Research Council for Health, Academy of Finland (Grant no 266314 and 310372 ). MH and YH were supported by the Environment Research and Technology Development Fund (S-14) of the Environmental Restoration and Conservation Agency . AT was supported by the Japan Society for the Promotion of Science (JSPS) Invitational Fellowships for Research in Japan ( S18149 ). Appendix A

Background Methodological information acknowledging safety of cardiac patients in controlled medical experiments are lacking. The descriptive report presents one good practice for considering safety in a randomized controlled study involving augmented cardiovascular strain among persons with coronary artery disease (CAD). Methods The patients were pre-selected by a cardiologist according to strictly defined selection criteria. Further confirmation of eligibility included screening of health. In addition, assessments of physical capacity by a graded bicycle ergometer test were implemented and safety monitored by an exercise physiologist and medical doctor. In this context, an emergency simulation was also carried out. A total of 18 CAD patients each underwent four different experimental interventions where either temperature (+ 22 °C and − 15 °C) and the level of exercise (rest and brisk walking) were employed for 30 min in random order (72 experiments). Baseline (20 min) and follow-up (60 min) measurements were conducted resting at + 22 °C. ECG, and brachial blood pressure were measured and perceived exertion and symptoms of chest pain inquired throughout the experiments. An emergency nurse was responsible for the health monitoring and at least two persons followed the patient throughout the experiment. A medical doctor was available on call for consultation. The termination criteria followed the generally accepted international guidelines for exercise testing and were planned prior to the experiments. Results The exercise test simulation revealed risks requiring changes in the study design and emergency response. The cardiovascular responses of the controlled trials were related to irregular HR, ST-depression or post-exercise hypotension. These were expected and the majority could be dealt on site by the research personnel and on call consultation. Only one patient was encouraged to seek for external health care consultation. Conclusions Appropriate prospective design is a key to safe implementation of controlled studies involving cardiac patients and stimulation of cardiovascular function. This includes careful selection of participants, sufficient and knowledgeable staff, as well as identifying possible emergency situations and the required responses. Trial registration ClinicalTrials ID: NCT02855905.

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.) Copyright © 2019 Massachusetts Medical Society., Funding text #1 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.) Funding text #2 Supported by the National Natural Science Foundation of China (grants 91843302 and 91643205, to Dr. Kan); the China Medical Board Collaborating Program (grant 16-250); the Medical Research Council, United Kingdom (grants MR/R013349/1 and MR/M022625/1, to Drs. Gasparrini, Sera, and Vicedo-Cabrera); the Career Development Fellowship of the Australian National Health and Medical Research Council (grants APP1107107 and APP1163693, to Dr. Guo); the Ministry of Education of Spain (grant PRX17/00705, to Dr. Tobias); the National Plan for I+D+I (grant PI15/00515), cofunded by the Instituto de Salud Carlos III Directorate General for Evaluation and the European Regional Development Fund (FEDER); the Global Research Laboratory (grant K21004000001-10A0500-00710 from the National Research Foundation of Korea, funded by the Ministry of Science, Information and Communication Technologies, to Dr. Kim); the Academy of Finland (grants 310372 and 310373, to Drs. Jaakkola and Ryti); the Estonian Ministry of Education and Research (grant IUT34-17, to Drs. Orru and Indermitte); the Czech Science Foundation (grant 18-22125S, to Drs. Kyselý and Urban); and a Professional Services Agreement with the Health Effects Institute, United States (to Dr. Cohen).View less Funding text #3 The authors’ affiliations are as follows: the School of Public Health, Key Laboratory of Public Health Safety of the Ministry of Education and National Health Commission Key Laboratory of Health Technology Assessment (C.L., R.C., H. Kan), the Department of Environmental Science and Engineering (J. Chen), Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (R.C., H. Kan), Fudan University, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine (S.T.), and Children’s Hospital of Fudan University, National Center for Children’s Health (H. Kan), Shanghai, the School of Public Health and Management, Binzhou Medical University, Yantai (Y.G.), the School of Public Health, Institute of Environment and Population Health, Anhui Medical University, Hefei (S.T.), and the Key Laboratory of Environment and Health, Ministry of Education, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (T.W.) — all in China; the Department of Public Health, Environments and Society (F.S., A.M.V.-C., A.M., A.G.) and the Centre for Statistical Methodology (A.G.), London School of Hygiene and Tropical Medicine, and the School of Population Health and Environmental Sciences, King’s College London (K.K.), London; the Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC (Y.G.), and the School of Public Health and Social Work, Queensland University of Technology, Brisbane (S.T.) — both in Australia; the Institute of Advanced Studies, University of São Paulo, São Paulo (M.S.Z.S.C., P.H.N.S.); the Air Health Science Division, Health Canada, and the School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON (E.L.); the Department of Public Health (P.M.) and the School of Nursing and Obstetrics (N.V.O.), Universidad de los Andes, Santiago, Chile; Hospital Vista Hermosa, Bogota, Colombia (S.O.G.); Santé Publique France, French National Public Health Agency, Saint Maurice, France (M.P.); the Department of Epidemiology, Lazio Regional Health Service–ASL Roma 1, Rome (M. Stafoggia, M. Scortichini); Karolinska Institute, Institute of Environmental Medicine, Stockholm (M. Stafoggia), and the Department of Public Health and Clinical Medicine, Umeå University, Umeå (B.F., C.Å., H.O.) — both in Sweden; the Department of Pediatric Infectious Diseases, Institute of Tropical Medicine, Nagasaki University, Nagasaki (M.H.), and the Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba (Y.H.) — both in Japan; the Department of Environmental Health, National Institute of Pub

Background The health burden associated with temperature is expected to increase due to a warming climate. Populations living in cities are likely to be particularly at risk, but the role of urban characteristics in modifying the direct effects of temperature on health is still unclear. In this contribution, we used a multi-country dataset to study effect modification of temperature–mortality relationships by a range of city-specific indicators. Methods We collected ambient temperature and mortality daily time-series data for 340 cities in 22 countries, in periods between 1985 and 2014. Standardized measures of demographic, socio-economic, infrastructural and environmental indicators were derived from the Organisation for Economic Co-operation and Development (OECD) Regional and Metropolitan Database. We used distributed lag non-linear and multivariate meta-regression models to estimate fractions of mortality attributable to heat and cold (AF%) in each city, and to evaluate the effect modification of each indicator across cities. Results Heat- and cold-related deaths amounted to 0.54% (95% confidence interval: 0.49 to 0.58%) and 6.05% (5.59 to 6.36%) of total deaths, respectively. Several city indicators modify the effect of heat, with a higher mortality impact associated with increases in population density, fine particles (PM2.5), gross domestic product (GDP) and Gini index (a measure of income inequality), whereas higher levels of green spaces were linked with a decreased effect of heat. Conclusions This represents the largest study to date assessing the effect modification of temperature–mortality relationships. Evidence from this study can inform public-health interventions and urban planning under various climate-change and urban-development scenarios., This work was primarily supported by the Medical Research Council—UK (MR/M022625/1). The following individual grants also supported this work: Y.G. was supported by the Career Development Fellowship of Australian National Health and Medical Research Council (APP1107107); A.T. was supported by the Ministry of Education of Spain (PRX17/00705); J.J.K.J. and N.R.I.R. were supported by the Research Council for Health, Academy of Finland (266314); Y.L.G. was supported by the National Health Research Institutes of Taiwan (NHRI-EM-106-SP03); M.L.B. was supported by a US Environmental Protection Agency Assistance Agreement awarded to Yale University (83587101).

There is accumulating evidence that prenatal exposure to air pollution disturbs fetal growth and development, but little is known about these effects in cold climates or their season-specific or joint effects. Our objective was to assess independent and joint effects of prenatal exposure to specific air pollutants on the risk of low birth weight (LBW). We utilized the 2568 children of the Espoo Cohort Study, born between 1984 and 1990 and living in the City of Espoo. We conducted stratified analyses for births during warm and cold seasons separately. We analyzed the effect estimates using multi-pollutant Poisson regression models with risk ratio (RR) as the measure of effect. The risk of LBW was related to exposure to CO (adjusted RR 1.44, 95% confidence interval [CI]: 1.04&ndash, 2.00) and exposure to O3 in the spring&ndash, summer season (1.82, 1.11&ndash, 2.96). There was also evidence of synergistic effects between CO and O3 (relative risk due to interaction (RERI), all year 1.08, 95% CI: 0.27&ndash, 4.94, spring&ndash, summer 3.97, 2.17&ndash, 25.85) and between PM2.5 and O3 (all year 0.72, &minus, 0.07&ndash, 3.60, spring&ndash, summer 2.80, 1.36&ndash, 19.88). We present new evidence of both independent and joint effects of prenatal exposure to low levels of air pollution in a cold climate on the risk of LBW.

Regular year-round exercise is recommended for patients with coronary artery disease (CAD). However, the combined effects of cold and moderate sustained exercise, both known to increase cardiac workload, on cardiovascular responses are not known. We tested the hypothesis that cardiac workload is increased, and evidence of ischemia would be observed during exercise in the cold in patients with CAD. Sixteen men (59.3 +/- 7.0 yr, means +/- SD) with stable CAD each underwent 4, 30 min exposures in a randomized order: seated rest and moderate-intensity exercise [walking, 60%-70% of max heart rate (HR)] performed at +22 degrees C and -15 degrees C. Systolic brachial blood pressure (SBP), HR, electrocardiogram (ECG), and skin temperatures were recorded throughout the intervention. Rate pressure product (RPP) and ECG parameters were obtained. The combined effects of cold and submaximal exercise were additive for SBP and RPP and synergistic for HR when compared with rest in a neutral environment. RPP (mmHg.beats/min) was 17% higher during exercise in the cold (18,080 +/- 3540) compared with neutral (15,490 +/- 2,940) conditions (P = 0.001). Only a few ST depressions were detected during exercise but without an effect of ambient temperature. The corrected QT interval increased while exercising in the cold compared with neutral temperature (P = 0.023). Recovery of postexercise blood pressure was similar regardless of temperature. Whole body exposure to cold during submaximal exercise results in higher cardiac workload compared with a neutral environment. Despite the higher RPP, no signs of myocardial ischemia or abnormal ECG responses were observed. The results of this study are useful for planning year-round exercise-based rehabilitation programs for stable CAD patients.

Background/Aim:The health effects of extreme temperatures are well documented at population level. Within the TREASURE project, a smartphone application developed to provide services to citizens du...

Background: Ambient air pollution from anthropogenic sources is a main cause of mortality from respiratory disease worldwide, but little is known about the role of pollen. Objective: To test a priori hypothesis that exposure to allergenic pollen from trees and grass increases the risk of death from respiratory diseases. Methods: We conducted a time-series analysis of the relations between daily levels of allergenic pollen and mortality from respiratory causes in the Helsinki Metropolitan Area, Finland, 1994-2014. The study population provided by the Statistics Finland comprised 153 378 deaths, 9 742 (6.4%) from respiratory causes. Daily (average) pollen counts for alder, birch, mugwort, and grass were from the Helsinki University Hospital monitoring stations and air quality data from the Helsinki Region Environmental Services Authority. The main outcome was daily respiratory mortality. Results: The average number of daily deaths was 20.0 (SD 4.78) for all causes, and 1.3 (SD1.25) for respiratory diseases. In quasi-Poisson regression analysis adjusting for long-term trends, ambient temperature, and main air pollutants, abundant daily concentrations of alder increased significantly the risk of death from respiratory diseases, with an 11.9% increase (95% CI 7.8-16.1) for previous day abundant level and 9.1% (3.2-15.3) for 0-4 days’ cumulative exposure. No associations were seen for other pollen. Conclusions: Our results provide new evidence of relation between daily levels of alder pollen and respiratory mortality. These findings identify an important global public health impact and the results support development of population-based prevention through alarm systems and personalised medical advice at the clinics.

The Paris Agreement binds all nations to undertake ambitious efforts to combat climate change, with the commitment to hold warming well below 2 degrees C in global mean temperature (GMT), relative to pre-industrial levels, and to pursue efforts to limit warming to 1.5 degrees C. The 1.5 degrees C limit constitutes an ambitious goal for which greater evidence on its benefits for health would help guide policy and potentially increase the motivation for action. Here we contribute to this gap with an assessment on the potential health benefits, in terms of reductions in temperature-related mortality, derived from the compliance to the agreed temperature targets, compared to more extreme warming scenarios. We performed a multi-region analysis in 451 locations in 23 countries with different climate zones, and evaluated changes in heat and cold-related mortality under scenarios consistent with the Paris Agreement targets (1.5 and 2 degrees C) and more extreme GMT increases (3 and 4 degrees C), and under the assumption of no changes in demographic distribution and vulnerability. Our results suggest that limiting warming below 2 degrees C could prevent large increases in temperature-related mortality in most regions worldwide. The comparison between 1.5 and 2 degrees C is more complex and characterized by higher uncertainty, with geographical differences that indicate potential benefits limited to areas located in warmer climates, where direct climate change impacts will be more discernible.

Background: Heatwaves are a critical public health problem. There will be an increase in the frequency and severity of heatwaves under changing climate. However, evidence about the impacts of climate change on heatwave-related mortality at a global scale is limited. Methods and findings: We collected historical daily time series of mean temperature and mortality for all causes or nonexternal causes, in periods ranging from January 1, 1984, to December 31, 2015, in 412 communities within 20 countries/regions. We estimated heatwave–mortality associations through a two-stage time series design. Current and future daily mean temperature series were projected under four scenarios of greenhouse gas emissions from 1971–2099, with five general circulation models. We projected excess mortality in relation to heatwaves in the future under each scenario of greenhouse gas emissions, with two assumptions for adaptation (no adaptation and hypothetical adaptation) and three scenarios of population change (high variant, median variant, and low variant). Results show that, if there is no adaptation, heatwave-related excess mortality is expected to increase the most in tropical and subtropical countries/regions (close to the equator), while European countries and the United States will have smaller percent increases in heatwave-related excess mortality. The higher the population variant and the greenhouse gas emissions, the higher the increase of heatwave-related excess mortality in the future. The changes in 2031–2080 compared with 1971–2020 range from approximately 2,000% in Colombia to 150% in Moldova under the highest emission scenario and high-variant population scenario, without any adaptation. If we considered hypothetical adaptation to future climate, under high-variant population scenario and all scenarios of greenhouse gas emissions, the heatwave-related excess mortality is expected to still increase across all the countries/regions except Moldova and Japan. However, the increase would be much smaller than the no adaptation scenario. The simple assumptions with respect to adaptation as follows: no adaptation and hypothetical adaptation results in some uncertainties of projections. Conclusions: This study provides a comprehensive characterisation of future heatwave-related excess mortality across various regions and under alternative scenarios of greenhouse gas emissions, different assumptions of adaptation, and different scenarios of population change. The projections can help decision makers in planning adaptation and mitigation strategies for climate change. © 2018 Guo et al. http://creativecommons.org/licenses/by/4.0/., We thank relevant institutes/agencies who provided data on mortality and weather conditions.

ObjectiveTo testa priorihypothesis of an association between season-specific cold spells and sudden cardiac death (SCD).MethodsWe conducted a case–crossover study of 3614 autopsy-verified cases of SCD in the Province of Oulu, Finland (1998–2011). Cold spell was statistically defined by applying an individual frequency distribution of daily temperatures at the home address during the hazard period (7 days preceding death) and 50 reference periods (same calendar days of other years) for each case using the home coordinates. Conditional logistic regression was applied to estimate ORs for the association between the occurrence of cold spells and the risk of SCD after controlling for temporal trends.ResultsThe risk of SCD was associated with a preceding cold spell (OR 1.33; 95% CI 1.00, 1.78). A greater number of cold days preceding death increased the risk of SCD approximately 19% per day (OR 1.19; 95% CI 1.07 to 1.32). The association was strongest during autumn (OR 2.51; 95% CI 1.27 to 4.96) and winter (OR 1.70; 95% CI 1.13 to 2.55) and lowest during summer (OR 0.42; 95% CI 0.15 to 1.18) and spring (OR 0.89; 95% CI 0.45 to 1.79). The association was stronger for ischaemic (OR 1.55; 95% CI 1.12 to 2.13) than for non-ischaemic SCD (OR 0.68; 95% CI 0.32 to 1.45) verified by medicolegal autopsy.ConclusionsOur results indicate that there is an association between cold spells and SCD, that this association is strongest during autumn, when the weather event is prolonged, and with cases suffering ischaemic SCD. These findings are subsumed with potential prevention via weather forecasting, medical advice and protective behaviour.

Sudden cardiac death (SCD) is the leading cause of death. The current paradigm in SCD requires the presence of an abnormal myocardial substrate and an internal or external transient factor that triggers cardiac arrest. Based on prior mechanistic evidence, we hypothesized that an unusually cold weather event (a cold spell) could act as an external factor triggering SCD. We tested potential effect modification of prior diagnoses and select pharmacological agents disrupting pathological pathways between cold exposure and death. The home coordinates of 2572 autopsy-verified cases of ischaemic SCD aged ≥35 in the Province of Oulu, Finland, were linked to 51 years of home-specific weather data. Based on conditional logistic regression, an increased risk of ischaemic SCD associated with a cold spell preceding death (OR 1.49; 95% CI: 1.06–2.09). Cases without a prior diagnosis of ischaemic heart disease seemed more susceptible to the effects of cold spells (OR 1.70; 95% CI: 1.13–2.56) than cases who had been diagnosed during lifetime (OR 1.14; 95% CI: 0.61–2.10). The use of aspirin, β-blockers, and/or nitrates, independently and in combinations decreased the risk of ischaemic SCD during cold spells. The findings open up new lines of research in mitigating the adverse health effects of weather.

Background There is some evidence that prenatal exposure to low-level air pollution increases the risk of preterm birth (PTB), but little is known about synergistic effects of different pollutants. Objectives We assessed the independent and joint effects of prenatal exposure to air pollution during the entire duration of pregnancy. Methods The study population consisted of the 2568 members of the Espoo Cohort Study, born between 1984 and 1990, and living in the City of Espoo, Finland. We assessed individual-level prenatal exposure to ambient air pollutants of interest at all the residential addresses from conception to birth. The pollutant concentrations were estimated both by using regional-to-city-scale dispersion modelling and land-use regression–based method. We applied Poisson regression analysis to estimate the adjusted risk ratios (RRs) with their 95% confidence intervals (CI) by comparing the risk of PTB among babies with the highest quartile (Q4) of exposure during the entire duration of pregnancy with those with the lower exposure quartiles (Q1-Q3). We adjusted for season of birth, maternal age, sex of the baby, family's socioeconomic status, maternal smoking during pregnancy, maternal exposure to environmental tobacco smoke during pregnancy, single parenthood, and exposure to other air pollutants (only in multi-pollutant models) in the analysis. Results In a multi-pollutant model estimating the effects of exposure during entire pregnancy, the adjusted RR was 1.37 (95% CI: 0.85, 2.23) for PM2.5 and 1.64 (95% CI: 1.15, 2.35) for O3. The joint effect of PM2.5 and O3 was substantially higher, an adjusted RR of 3.63 (95% CI: 2.16, 6.10), than what would have been expected from their independent effects (0.99 for PM2.5 and 1.34 for O3). The relative risk due to interaction (RERI) was 2.30 (95% CI: 0.95, 4.57). Discussion Our results strengthen the evidence that exposure to fairly low-level air pollution during pregnancy increases the risk of PTB. We provide novel observations indicating that individual air pollutants such as PM2.5 and O3 may act synergistically potentiating each other's adverse effects.

Background There is substantial evidence that mortality increases in low temperatures. Less is known about the role of prolonged cold periods denoted as cold spells. Objective We conducted the first systematic review and meta-analysis to summarize the evidence on the adverse health effects of cold spells in varying climates. Data sources and extraction Four databases (Ovid Medline, PubMed, Scopus, Web of Science) were searched for all years and languages available. “Cold spell” was defined as an event below a temperature threshold lasting for a minimum duration of 2 days. Of 1,527 identified articles, 26 satisfied our eligibility criteria for the systematic review, and 9 were eligible for meta-analyses. The articles were grouped by the three main study questions into Overall-effect Group, Added-effect Group, and Temperature-change-effect Group. Data synthesis Based on random-effects models in the meta-analyses, cold spells were associated with increased mortality from all or all nonaccidental causes (summary rate ratio = 1.10; 95% CI: 1.04, 1.17 based on 9 estimates from five studies), cardiovascular diseases (1.11; 95% CI: 1.03, 1.19; 12 estimates from eight studies), and respiratory diseases (1.21; 95% CI: 0.97, 1.51; 8 estimates from four studies). Estimated associations were stronger for people ≥ 65 years of age (1.06; 95% CI: 1.00, 1.12) than for people 0–64 years of age (1.01; 95% CI: 1.00, 1.03). Study-specific effect estimates from a limited number of studies suggested an increased morbidity related to cold spells, but it was not possible to quantitatively summarize the evidence. Conclusions Cold spells are associated with increased mortality rates in populations around the world. The body of evidence suggests that cold spells also have other adverse health effects. There was substantial heterogeneity among the studies, which should be taken into account in the interpretation of the results. Citation Ryti NR, Guo Y, Jaakkola JJ. 2016. Global association of cold spells and adverse health effects: a systematic review and meta-analysis. Environ Health Perspect 124:12–22; http://dx.doi.org/10.1289/ehp.1408104

Neuronostatin, a recently discovered peptide encoded by somatostatin gene, is involved in regulation of neuronal function, blood pressure, food intake, and drinking behavior. However, the biological effects of neuronostatin on cardiac myocytes are not known, and the intracellular signaling mechanisms induced by neuronostatin remain unidentified. We analyzed the effect of neuronostatin in isolated perfused rat hearts and in cultured primary cardiomyocytes. Neuronostatin infusion alone had no effect on left ventricular (LV) contractile function or on isoprenaline- or preload-induced increase in cardiac contractility. However, infusion of neuronostatin significantly decreased the positive inotropic response to endothelin-1 (ET-1). This was associated with an increase in phosphorylation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase (JNK). Treatment of both neonatal and adult cardiomyocytes with neuronostatin resulted in reduced cardiomyocyte viability. Inhibition of JNK further increased the neuronostatin-induced cell death. We conclude that neuronostatin regulates cardiac contractile function and cardiomyocyte survival. Receptors for neuronostatin need to be identified to further characterize the biological functions of the peptide.

Background: Climate change can directly affect human health by varying exposure to non-optimal outdoor temperature. However, evidence on this direct impact at a global scale is limited, mainly due to issues in modelling and projecting complex and highly heterogeneous epidemiological relationships across different populations and climates. Methods: We collected observed daily time series of mean temperature and mortality counts for all causes or non-external causes only, in periods ranging from Jan 1, 1984, to Dec 31, 2015, from various locations across the globe through the Multi-Country Multi-City Collaborative Research Network. We estimated temperature–mortality relationships through a two-stage time series design. We generated current and future daily mean temperature series under four scenarios of climate change, determined by varying trajectories of greenhouse gas emissions, using five general circulation models. We projected excess mortality for cold and heat and their net change in 1990–2099 under each scenario of climate change, assuming no adaptation or population changes. Findings: Our dataset comprised 451 locations in 23 countries across nine regions of the world, including 85 879 895 deaths. Results indicate, on average, a net increase in temperature-related excess mortality under high-emission scenarios, although with important geographical differences. In temperate areas such as northern Europe, east Asia, and Australia, the less intense warming and large decrease in cold-related excess would induce a null or marginally negative net effect, with the net change in 2090–99 compared with 2010–19 ranging from −1·2% (empirical 95% CI −3·6 to 1·4) in Australia to −0·1% (−2·1 to 1·6) in east Asia under the highest emission scenario, although the decreasing trends would reverse during the course of the century. Conversely, warmer regions, such as the central and southern parts of America or Europe, and especially southeast Asia, would experience a sharp surge in heat-related impacts and extremely large net increases, with the net change at the end of the century ranging from 3·0% (−3·0 to 9·3) in Central America to 12·7% (−4·7 to 28·1) in southeast Asia under the highest emission scenario. Most of the health effects directly due to temperature increase could be avoided under scenarios involving mitigation strategies to limit emissions and further warming of the planet. Interpretation: This study shows the negative health impacts of climate change that, under high-emission scenarios, would disproportionately affect warmer and poorer regions of the world. Comparison with lower emission scenarios emphasises the importance of mitigation policies for limiting global warming and reducing the associated health risks. Funding: UK Medical Research Council. © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license, This work was primarily supported by the Medical Research Council-UK (grant MR/M022625/1). The following individual grants also supported this work: YG was supported by the Career Development Fellowship of Australian National Health and Medical Research Council (grant APP1107107); AT was supported by the Ministry of Education of Spain (grant PRX17/00705); VH was supported by the German Federal Ministry of Education and Research (grant 01LS1201A2); JK was supported by the Czech Science Foundation (grant 16-22000S); JJKJ and NRIR were supported by the Research Council for Health, Academy of Finland (grant 266314); MH, YLG, C-fW, YH, and HKi were supported by the Global Research Laboratory (grant K21004000001-10A0500-00710) through the National Research Foundation of Korea; YH was supported by the Environment Research and Technology Development Fund (S-14) of the Ministry of the Environment, Japan; YLG was supported by the National Health Research Institutes of Taiwan (grant NHRI-EM-106-SP03); and MLB was supported by a US Environmental Protection Agency Assistance Agreement awarded to Yale University (grant 83587101).