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In this article, we present a comprehensive compilation of open access daily time-series datasets tailored to assess the temperature-mortality association. The data consists of daily mortality counts and average ambient temperature at various levels of geographic aggregation, including data from four cities, ten regions, and two counties, which have been utilised in previously published studies. These datasets are applicable for time-series regression analysis to estimate location-specific temperature-mortality associations. Additionally, the availability of data from multiple geographical locations enabled the exploration of geographical differences by pooling associations using meta-analysis. This compilation aims to serve as a valuable resource for researchers, educators, and students, facilitating their application of time-series regression modelling for research endeavours and training activities.

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

Background: Temperature variability (TV) is associated with increased mortality risk. However, it is still unknown whether intra-day or inter-day TV has different effects. Objectives: We aimed to assess the association of intra-day TV and inter-day TV with all-cause, cardiovascular, and respiratory mortality. Methods: We collected data on total, cardiovascular, and respiratory mortality and meteorology from 758 locations in 47 countries or regions from 1972 to 2020. We defined inter-day TV as the standard deviation (SD) of daily mean temperatures across the lag interval, and intra-day TV as the average SD of minimum and maximum temperatures on each day. In the first stage, inter-day and intra-day TVs were modelled simultaneously in the quasi-Poisson time-series model for each location. In the second stage, a multi-level analysis was used to pool the location-specific estimates. Results: Overall, the mortality risk due to each interquartile range [IQR] increase was higher for intra-day TV than for inter-day TV. The risk increased by 0.59% (95% confidence interval [CI]: 0.53, 0.65) for all-cause mortality, 0.64% (95% CI: 0.56, 0.73) for cardiovascular mortality, and 0.65% (95% CI: 0.49, 0.80) for respiratory mortality per IQR increase in intra-day TV0–7 (0.9 °C). An IQR increase in inter-day TV0–7 (1.6 °C) was associated with 0.22% (95% CI: 0.18, 0.26) increase in all-cause mortality, 0.44% (95% CI: 0.37, 0.50) increase in cardiovascular mortality, and 0.31% (95% CI: 0.21, 0.41) increase in respiratory mortality. The proportion of all-cause deaths attributable to intra-day TV0–7 and inter-day TV0–7 was 1.45% and 0.35%, respectively. The mortality risks varied by lag interval, climate area, season, and climate type. Conclusions: Our results indicated that intra-day TV may explain the main part of the mortality risk related to TV and suggested that comprehensive evaluations should be proposed in more countries to help protect human health.

Assessing the association between temperature frequency and mortality can provide insights into human adaptation to local ambient temperatures. We collected daily time-series data on mortality and temperature from 757 locations in 47 countries/regions during 1979–2020. We used a two-stage time series design to assess the association between temperature frequency and all-cause mortality. The results were pooled at the national, regional, and global levels. We observed a consistent decrease in the risk of mortality as the normalized frequency of temperature increases across the globe. The average increase in mortality risk comparing the 10th to 100th percentile of normalized frequency was 13.03% (95% CI: 12.17–13.91), with substantial regional differences (from 4.56% in Australia and New Zealand to 33.06% in South Europe). The highest increase in mortality was observed for high-income countries (13.58%, 95% CI: 12.56–14.61), followed by lower-middle-income countries (12.34%, 95% CI: 9.27–15.51). This study observed a declining risk of mortality associated with higher temperature frequency. Our findings suggest that populations can adapt to their local climate with frequent exposure, with the adapting ability varying geographically due to differences in climatic and socioeconomic characteristics.

Background: The epidemiological evidence on the interaction between heat and ambient air pollution on mortality is still inconsistent. Objectives: To investigate the interaction between heat and ambient air pollution on daily mortality in a large dataset of 620 cities from 36 countries. Methods: We used daily data on all-cause mortality, air temperature, particulate matter ≤ 10 μm (PM10), PM ≤ 2.5 μm (PM2.5), nitrogen dioxide (NO2), and ozone (O3) from 620 cities in 36 countries in the period 1995–2020. We restricted the analysis to the six consecutive warmest months in each city. City-specific data were analysed with over-dispersed Poisson regression models, followed by a multilevel random-effects meta-analysis. The joint association between air temperature and air pollutants was modelled with product terms between non-linear functions for air temperature and linear functions for air pollutants. Results: We analyzed 22,630,598 deaths. An increase in mean temperature from the 75th to the 99th percentile of city-specific distributions was associated with an average 8.9 % (95 % confidence interval: 7.1 %, 10.7 %) mortality increment, ranging between 5.3 % (3.8 %, 6.9 %) and 12.8 % (8.7 %, 17.0 %), when daily PM10 was equal to 10 or 90 μg/m3, respectively. Corresponding estimates when daily O3 concentrations were 40 or 160 μg/m3 were 2.9 % (1.1 %, 4.7 %) and 12.5 % (6.9 %, 18.5 %), respectively. Similarly, a 10 μg/m3 increment in PM10 was associated with a 0.54 % (0.10 %, 0.98 %) and 1.21 % (0.69 %, 1.72 %) increase in mortality when daily air temperature was set to the 1st and 99th city-specific percentiles, respectively. Corresponding mortality estimate for O3 across these temperature percentiles were 0.00 % (-0.44 %, 0.44 %) and 0.53 % (0.38 %, 0.68 %). Similar effect modification results, although slightly weaker, were found for PM2.5 and NO2. Conclusions: Suggestive evidence of effect modification between air temperature and air pollutants on mortality during the warm period was found in a global dataset of 620 cities.

Background: Evidence on the potential interactive effects of heat and ambient air pollution on cause-specific mortality is inconclusive and limited to selected locations. Objectives: We investigated the effects of heat on cardiovascular and respiratory mortality and its modification by air pollution during summer months (six consecutive hottest months) in 482 locations across 24 countries. Methods: Location-specific daily death counts and exposure data (e.g., particulate matter with diameters ≤ 2.5 µm [PM2.5]) were obtained from 2000 to 2018. We used location-specific confounder-adjusted Quasi-Poisson regression with a tensor product between air temperature and the air pollutant. We extracted heat effects at low, medium, and high levels of pollutants, defined as the 5th, 50th, and 95th percentile of the location-specific pollutant concentrations. Country-specific and overall estimates were derived using a random-effects multilevel meta-analytical model. Results: Heat was associated with increased cardiorespiratory mortality. Moreover, the heat effects were modified by elevated levels of all air pollutants in most locations, with stronger effects for respiratory than cardiovascular mortality. For example, the percent increase in respiratory mortality per increase in the 2-day average summer temperature from the 75th to the 99th percentile was 7.7% (95% Confidence Interval [CI] 7.6–7.7), 11.3% (95%CI 11.2–11.3), and 14.3% (95% CI 14.1–14.5) at low, medium, and high levels of PM2.5, respectively. Similarly, cardiovascular mortality increased by 1.6 (95%CI 1.5–1.6), 5.1 (95%CI 5.1–5.2), and 8.7 (95%CI 8.7–8.8) at low, medium, and high levels of O3, respectively. Discussion: We observed considerable modification of the heat effects on cardiovascular and respiratory mortality by elevated levels of air pollutants. Therefore, mitigation measures following the new WHO Air Quality Guidelines are crucial to enhance better health and promote sustainable development.

Abstract Desert dust and sandstorms are recurring environmental phenomena that are reported to produce serious health risks worldwide. This scoping review was conducted to identify the most likely health effects of desert dust and sandstorms and the methods used to characterize desert dust exposure from the existing epidemiological literature. We systematically searched PubMed/MEDLINE, Web of Science, and Scopus to identify studies that reported the effects of desert dust and sandstorms on human health. Search terms referred to desert dust or sandstorm exposure, names of major deserts, and health outcomes. Health effects were cross‐tabulated with study design variables (e.g., epidemiological design and methods to quantify dust exposure), desert dust source, health outcomes and conditions. We identified 204 studies that met the inclusion criteria for the scoping review. More than half of the studies (52.9%) used a time‐series study design. However, we found a substantial variation in the methods used to identify and quantify desert dust exposure. The binary metric of dust exposure was more frequently used than the continuous metric for all desert dust source locations. Most studies (84.8%) reported significant associations between desert dust and adverse health effects, mainly for respiratory and cardiovascular mortality and morbidity causes. Although there is a large body of evidence on the health effects of desert dust and sandstorms, the existing epidemiological studies have significant limitations related to exposure measurement and statistical analysis that potentially contribute to inconsistencies in determining the effect of desert dust on human health.

Abstract Epidemiological analyses of health risks associated with non-optimal temperature are traditionally based on ground observations from weather stations that offer limited spatial and temporal coverage. Climate reanalysis represents an alternative option that provide complete spatio-temporal exposure coverage, and yet are to be systematically explored for their suitability in assessing temperature-related health risks at a global scale. Here we provide the first comprehensive analysis over multiple regions to assess the suitability of the most recent generation of reanalysis datasets for health impact assessments and evaluate their comparative performance against traditional station-based data. Our findings show that reanalysis temperature from the last ERA5 products generally compare well to station observations, with similar non-optimal temperature-related risk estimates. However, the analysis offers some indication of lower performance in tropical regions, with a likely underestimation of heat-related excess mortality. Reanalysis data represent a valid alternative source of exposure variables in epidemiological analyses of temperature-related risk.

Possible effects of weather conditions on COVID-19 transmission are debated. Here, the authors analyse data from early in the pandemic and show that although temperature and humidity had small effects on transmission, they were far out-weighed by the effects of non-pharmaceutical interventions.

Summary: Background: 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. Methods: We collected daily ambient temperature and mortality data for 452 locations in 24 countries and used Enhanced Vegetation Index (EVI) as the greenspace measurement. We used distributed lag non-linear model to estimate the heat-mortality relationship in each city and the estimates were pooled adjusting for city-specific average temperature, city-specific temperature range, city-specific population density, and gross domestic product (GDP). The effect modification of greenspace was evaluated by comparing the heat-related mortality risk for different greenspace groups (low, medium, and high), which were divided into terciles among 452 locations. Findings: Cities with high greenspace value had the lowest heat-mortality relative risk of 1·19 (95% CI: 1·13, 1·25), while the heat-related relative risk was 1·46 (95% CI: 1·31, 1·62) for cities with low greenspace when comparing the 99th temperature and the minimum mortality temperature. A 20% increase of greenspace is associated with a 9·02% (95% CI: 8·88, 9·16) decrease in the heat-related attributable fraction, and if this association is causal (which is not within the scope of this study to assess), such a reduction could save approximately 933 excess deaths per year in 24 countries. Interpretation: Our findings can inform communities on the potential health benefits of greenspaces in the urban environment and mitigation measures regarding the impacts of climate change. Funding: 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.

The data presented in this article is part in essence of a more extensive dataset aimed at evaluating patterns of change in the temperature–mortality relationship on population health in the city of Valencia, Spain on population health in the city of Valencia, Spain. The complete dataset was used in the framework of the European multi-city project PHASE (Public Health Adaptation Strategies to Extreme weather events) [1]. The data includes daily counts of all-cause mortality, excluding external causes and cardiovascular and respiratory diseases. All-cause mortality is also classified by gender and age groups. Besides temperature, we included other meteorological variables and air pollutants from the PHASE dataset, as well as influenza epidemics. The variable Saharan dust events was also added. All these data were collected from public Governmental data repositories accessible under request. The dataset of this article provides a basis for comparison with similar models for time-series regression, allowing researchers to integrate additional model components without duplication of effort.

Abstract Background Globally too many mothers and babies die during childbirth; 98% of maternal deaths are avoidable. Skilled clinicians can reduce these deaths; however, there is a world-wide shortage of maternity healthcare workers. Malawi has enough to deliver 20% of its maternity care. A motivating work environment is important for healthcare worker retention. To inform a future trial, we aimed to assess the feasibility of implementing a motivational intervention (Appreciative Inquiry) to improve the working lives of maternity healthcare workers and patient satisfaction in Malawi. Methods Three government hospitals participated over 1 year. Its effectiveness was assessed through: a monthly longitudinal survey of working life using psychometrically validated instruments (basic psychological needs, job satisfaction and work-related quality of life); a before and after questionnaire of patient satisfaction using a patient satisfaction tool validated in low-income settings with a maximum score of 80; and a qualitative template analysis encompassing ethnographic data, semi-structured interviews and focus groups with staff. Results The intervention was attended by all 145 eligible staff, who also participated in the longitudinal study. The general trend was an increase in the scores for each scale except for the basic psychological needs score in one site. Only one site demonstrated strong evidence for the intervention working in the work-related quality of life scales. Pre-intervention, 162 postnatal women completed the questionnaire; post-intervention, 191 postnatal women participated. Patient satisfaction rose in all three sites; referral hospital 4.41 rise (95% CI 1.89 to 6.95), district hospital 10.22 (95% CI 7.38 to 13.07) and community hospital 13.02 (95% CI 10.48 to 15.57). The qualitative data revealed that staff felt happier, that their skills (especially communication) had improved, behaviour had changed and systems had developed. Conclusions We have shown that it is possible to implement Appreciative Inquiry in government facilities in Malawi, which has the potential to change the way staff work and improve patient satisfaction. The mixed methods approach revealed important findings including the importance of staff relationships. We have identified clear implementation elements that will be important to measure in a future trial such as implementation fidelity and inter-personal relationship factors.

Summary: 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.

Abstract Background Regression analyses of time series of disease counts on environmental determinants are a prominent component of environmental epidemiology. For planning such studies, it can be useful to predict the precision of estimated coefficients and power to detect associations of given magnitude. Existing generic approaches for this have been found somewhat complex to apply and do not easily extend to multiple series studies analysed in two stages. We have sought a simpler approximate approach which can easily extend to multiple series and give insight into factors determining precision. Methods We derive approximate expressions for precision and hence power in single and multiple time series studies of counts from basic statistical theory, compare the precision predicted by these with that estimated by analysis in real data from 51 cities of varying size, and illustrate the use of these estimators in a realistic planning scenario. Results In single series studies with Poisson outcome distribution, precision and power depend only on the usable variation of exposure (i.e. that conditional on covariates) and the total number of disease events, regardless of how many days those are spread over. In multiple time series (eg multi-city) studies focusing on the meta-analytic mean coefficient, the usable exposure variation and the total number of events (in all series) are again the sole determinants if there is no between-series heterogeneity or within-series overdispersion. With heterogeneity, its extent and the number of series becomes important. For all but the crudest approximation the estimates of standard errors were on average within + 20% of those estimated in full analysis of actual data. Conclusions Predicting precision in coefficients from a planned time series study is possible simply and given limited information. The total number of disease events and usable exposure variation are the dominant factors when overdispersion and between-series heterogeneity are low.

Objectives Recreational physical activity is an integral part of our society, and the injuries caused by sports activities are a concern for public health. We studied the effect of outdoor ambient temperature on hospital emergency department visits caused by sports injuries in Madrid, Spain, and accounted for its seasonal changes.Methods We used a time-series design. Data was analysed with quasi-Poisson regression models. We calculated the proportion of emergency visits attributable to seasonal changes before and after adjusting for daily ambient temperature. We modelled the association between emergency visits and temperature using distributed lag non-linear models.Results The proportion of emergency visits attributable to seasonal changes was 24.1% and decreased to 7.6% after adjusting for temperature. We found a high risk of emergency visits associated with cold and hot temperatures, whereas the risk was higher for heat.Conclusion Sports and recreational physical activity injuries are not rare events; therefore, appropriate healthcare decisions should consider the impact of outdoor ambient temperature and seasonal changes.

Summary: 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.

Abstract Background Vitamin D deficiency has been associated with an increased risk of abnormal pregnancy implantation leading to obstetric complications such as pre-eclampsia and fetal growth restriction. However, the effect of vitamin D on reproductive treatment outcomes in couples undergoing assisted reproductive treatment is poorly understood. This study investigates the association between vitamin D and reproductive treatment outcomes in women undergoing assisted reproductive treatments? Methods A prospective cohort study conducted at a large tertiary teaching hospital, United Kingdom. Five hundred women undergoing assisted reproductive treatment were recruited between September 2013 and September 2015. All participants had their serum vitamin D measured and their reproductive treatment outcomes collated. Women were categorised in to three groups: vitamin D replete (> 75 nmol/L), insufficient (50-75 nmol/L) and deficient (

Summary: 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. Funding: EU Horizon 2020, UK Medical Research Council, and Natural Environment Research Council.

Background: The use of obstetric early warning systems (OEWS) are recommended as an adjunct to reduce maternal morbidity and mortality. The aim of this review was to document the variation in OEWS trigger thresholds and the quality of information included within accompanying escalation protocols. Methods: A review of OEWS charts and escalation policies across consultant-led maternity units in the UK (n = 147) was conducted. OEWS charts were analysed for variation in the values of physiological parameters triggering different levels of clinical escalation. Relevant data within the escalation protocols were also searched for: urgency of clinical response; seniority of responder; frequency of on-going clinical monitoring; and clinical setting recommended for on-going care. Results: The values of physiological parameters triggering specific clinical responses varied significantly between OEWS. Only 99 OEWS charts (67.3%) had an escalation protocol as part of the chart. For 29 charts (19.7%), the only escalation information included was generic, for example to “contact a doctor if triggers”. Only 76 (51.7%) charts detailed the required seniority of responder, 37 (25.2%) the frequency for on-going clinical monitoring, eight (5.4%) the urgency of clinical response and two (1.4%) the recommended clinical setting for on-going care. Conclusion: The observed variations in the trigger thresholds used in OEWS charts and the quality of information included within the accompanying escalation protocols is likely to lead to suboptimal detection and response to clinical deterioration during pregnancy and the post-partum period. The development of a national OEWS and escalation protocol would help to standardise care across obstetric units.

Vehicular traffic is one of the major sources of air pollution in European cities. This work aims to understand which characteristics of the urban environment could influence mobility-related air pollution, quantify the health impacts of exposure to traffic-derived PM2.5 and NO2 concentrations, and assess the potential health benefits expected from traffic interventions. The health benefits modeled are intended to provide a set of comparable data to support decision-makers and encourage informed decision-making to design healthier cities. Targeting a large geographical coverage, 12 European cities from 9 countries were comparatively assessed in terms of mean daily traffic volume/area, the number of public transport stops/area, and the percentage of green and outdoor leisure areas, among other urban indicators. This was implemented using an open-source data mining tool, which was seen as a useful engine to identify potential strategies to improve air quality. The comparison of urban indicators in the selected cities evidenced two trends: (a) cities with the most heterogeneous distribution of public transport stops, as an indicator of poor accessibility, are also those with the lowest proportion of km dedicated to cycleways and footways, highlighting the need in these cities for more sustainable mobility management; and (b) the percentage of green and outdoor leisure areas may influence the share of journeys by bicycle, pointing out that promoting the perception of green routes is relevant to enhance the potential of active transport modes. Socioeconomic factors can be key determinants of the urban indicators and would need further consideration. For the health impact assessment (HIA), two baseline scenarios were evaluated and compared. One is based on mean annual traffic contributions to PM2.5 concentrations in each target city (ranging between 1.9 and 13 µg/m3), obtained from the literature, and the second is grounded on mean annual NO2 concentrations at all available traffic and urban background stations within each city (17.2–83.5 µg/m3), obtained from the European Environment Agency database. The intervention scenarios modeled were designed based on traffic mitigation strategies in the literature, and set to ranges of 6–50% in traffic-derived PM2.5 concentrations and of 4–12.5% in NO2 concentrations. These scenarios could result in only a 1.7% (0.6–4%) reduction in premature mortality due to exposure to traffic-derived PM2.5, and 1.0% (0.4–2%) due to exposure to NO2, as the mean for all the cities. This suggests that more ambitious pollution abatement strategies should be targeted.

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. Funding: Korea Ministry of Environment.

Objectives To assess if there is any association between hyperemesis gravidarum (HG), psychological morbidity and infant bonding and to quantify any psychosocial consequences of HG.Design Two-point prospective case–control, multicentre survey study with antenatal and postnatal data collection.Setting Three London hospitals.Participants Pregnant women at ≤12 completed weeks gestation recruited consecutively over 2 years. Women with HG were recruited at the time of admission; controls recruited from a low risk antenatal clinic. 106 women were recruited to the case group and 108 to the control. Response rates at antenatal data collection were 87% and 85% in the case and control groups, respectively. Postnatally, the response rate was 90% in both groups.Primary and secondary outcome measures Primary outcomes were psychological morbidity in the antenatal and postnatal periods, infant bonding in the postnatal period and psychosocial implications of HG. Secondary outcomes were the effects of severity and longevity of HG and assessment of correlation between Edinburgh Postnatal Depression Scale scores and maternal-to-infant bonding scores.Results Antenatally, 49% of cases had probable depression compared with 6% of controls (OR 14.4 (5.29 to 39.44)). Postnatally, 29% of cases had probable depression versus 7% of controls (OR 5.2 (1.65 to 17.21)). There was no direct association between HG and infant bonding. 53% of women in the HG group reported needing four or more weeks of sick leave compared with 2% in the control group (OR 60.5 (95% CI 8.4 to 2535.6)).Conclusions Long-lasting psychological morbidity associated with HG was evident. Significantly more women in the case group sought help for mental health symptoms in the antenatal period, however very few were diagnosed with or treated for depression in pregnancy or referred to specialist perinatal mental health services. HG did not directly affect infant bonding. Women in the case group required long periods off work, highlighting the socioeconomic impact of HG.

Introduction Internal temporomandibular joint (TMJ) disorders are present in approximately 80% of patients with symptomatic temporomandibular disorders. Among the minimally invasive therapies, we find the intra-articular infiltration of substances, such as corticosteroids, hyaluronic acid or platelet-rich plasma accompanied or not by an arthrocentesis. There are several studies on minimally invasive therapy for internal TMJ disorders; however, none compares the effectiveness of the different intra-articular corticosteroids to each other.The purpose of this study is to evaluate the effectiveness of the different intra-articular corticosteroids for the treatment of internal disorders of the TMJ and compare them to each other or to other minimally invasive therapies.Methods and analysis A systematic search will be carried out up to December 2019 in the electronic databases: Medline, Cochrane Library, EMBASE, SCOPUS and LILACS.Randomised clinical trials evaluating patients with internal disorders of the TMJ, with intra-articular corticosteroid therapy and comparing these to each other and/or to other minimally invasive therapy will be included. The main outcomes will be pain and range of motion measured through validated scales.Two review authors will independently screen search results, extract data from included studies and assess the risk of bias in those studies using the Revised Cochrane Risk of Bias Tool (RoB 2.0). In the case of any discrepancy and failure to reach consensus, this will be resolved by a third reviewer.A network meta-analysis will be conducted based on direct comparisons to generate indirect comparisons of the different treatments. Data will be combined in a meta-analysis using a random effects model.The principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system will be used to assess the overall quality of the body of evidence associated with the main results.Ethics and dissemination This protocol will not require ethical approval. The results of this review will be disseminated through peer-reviewed publications.Trial registration number CRD42019129014.

Background: Temporal variation of temperature-health associations depends on the combination of two pathways: pure adaptation to increasingly warmer temperatures due to climate change, and other attenuation mechanisms due to non-climate factors such as infrastructural changes and improved health care. Disentangling these pathways is critical for assessing climate change impacts and for planning public health and climate policies. We present evidence on this topic by assessing temporal trends in cold- and heat-attributable mortality risks in a multi-country investigation. Methods: Trends in country-specific attributable mortality fractions (AFs) for cold and heat (defined as below/above minimum mortality temperature, respectively) in 305 locations within 10 countries (1985–2012) were estimated using a two-stage time-series design with time-varying distributed lag non-linear models. To separate the contribution of pure adaptation to increasing temperatures and active changes in susceptibility (non-climate driven mechanisms) to heat and cold, we compared observed yearly-AFs with those predicted in two counterfactual scenarios: trends driven by either (1) changes in exposure-response function (assuming a constant temperature distribution), (2) or changes in temperature distribution (assuming constant exposure-response relationships). This comparison provides insights about the potential mechanisms and pace of adaptation in each population. Results: Heat-related AFs decreased in all countries (ranging from 0.45–1.66% to 0.15–0.93%, in the first and last 5-year periods, respectively) except in Australia, Ireland and UK. Different patterns were found for cold (where AFs ranged from 5.57–15.43% to 2.16–8.91%), showing either decreasing (Brazil, Japan, Spain, Australia and Ireland), increasing (USA), or stable trends (Canada, South Korea and UK). Heat-AF trends were mostly driven by changes in exposure-response associations due to modified susceptibility to temperature, whereas no clear patterns were observed for cold. Conclusions: Our findings suggest a decrease in heat-mortality impacts over the past decades, well beyond those expected from a pure adaptation to changes in temperature due to the observed warming. This indicates that there is scope for the development of public health strategies to mitigate heat-related climate change impacts. In contrast, no clear conclusions were found for cold. Further investigations should focus on identification of factors defining these changes in susceptibility. Keywords: Climate change, Heat, Cold, Adaptation, Mortality

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. Keywords: Projection, Mortality, Climate change, Regional variation, Vulnerability

Introduction Desert dust concentrations raise concerns about adverse effects on human health. During the last decade, special attention has been given to mineral dust particles from desert dust and sand storms. However, evidence from previous reviews reported inconclusive results on their health effects and the biological mechanism remains unclear. We aim to systematically synthesise evidence on the health effects of desert dust and sand storms accounting for the relevant desert dust patterns from source areas and emissions, transport and composition.Methods an analysis We will conduct a systematic review that investigated the health effects of desert dust and sand storms in any population. The search will be performed for any eligible studies from previous reviews and selected electronic databases until 2018. Study selection and reporting will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data from individual studies will be extracted using a standardised data extraction form. Quality of the studies will be assessed using a risk of bias tool for environmental exposures developed by experts convened by the WHO. A meta-analysis will be performed by calculating the appropriate effect measures of association for binary and continuous outcomes from individual studies. Subgroup analyses will be performed by geographical areas to account for desert dust patterns.Ethics and dissemination No primary data will be collected. For this reason, no formal ethical approval is required. This systematic review will help to fill the research gaps in the knowledge of desert dust on human health. The results will be disseminated through a WHO peer-reviewed publication and a conference presentation.PROSPERO registration number CRD42018091809

Background: Postpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. Prophylactic uterotonic drugs can reduce blood loss and are routinely recommended. There are several uterotonic drugs for preventing PPH, but it is still debatable which drug or combination of drugs is the most effective. Objectives: To identify the most effective and cost-effective uterotonic drug(s) to prevent PPH, and generate a ranking according to their effectiveness and side-effect profile. Methods: The Cochrane Pregnancy and Childbirth’s Trials Register (1 June 2015), ClinicalTrials.gov and the World Health Organization (WHO)’s International Clinical Trials Registry Platform (ICTRP) were searched for unpublished trial reports (30 June 2015). In addition, reference lists of retrieved studies (updated October 2017) were searched for randomised trials evaluating uterotonic drugs for preventing PPH. The study estimated relative effects and rankings for preventing PPH, defined as blood loss of ≥ 500 ml and ≥ 1000 ml. Pairwise meta-analyses and network meta-analysis were performed to determine the relative effects and rankings of all available drugs and combinations thereof [ergometrine, misoprostol (Cytotec®; Pfizer Inc., New York, NY, USA), misoprostol plus oxytocin (Syntocinon®; Novartis International AG, Basel, Switzerland), carbetocin (Pabal®; Ferring Pharmaceuticals, Saint-Prex, Switzerland), ergometrine plus oxytocin (Syntometrine®; Alliance Pharma plc, Chippenham, UK), oxytocin, and a placebo or no treatment]. Primary outcomes were stratified according to the mode of birth, prior risk of PPH, health-care setting, drug dosage, regimen and route of drug administration. Sensitivity analyses were performed according to study quality and funding source, among others. A model-based economic evaluation compared the relative cost-effectiveness separately for vaginal births and caesareans with or without including side effects. Results: From 137 randomised trials and 87,466 women, ergometrine plus oxytocin, carbetocin and misoprostol plus oxytocin were found to reduce the risk of PPH blood loss of ≥ 500 ml compared with the standard drug, oxytocin [ergometrine plus oxytocin: risk ratio (RR) 0.69, 95% confidence interval (CI) 0.57 to 0.83; carbetocin: RR 0.72, 95% CI 0.52 to 1.00; misoprostol plus oxytocin: RR 0.73, 95% CI 0.6 to 0.9]. Each of these three strategies had 100% cumulative probability of being ranked first, second or third most effective. Oxytocin was ranked fourth, with an almost 0% cumulative probability of being ranked in the top three. Similar rankings were noted for the reduction of PPH blood loss of ≥ 1000 ml (ergometrine plus oxytocin: RR 0.77, 95% CI 0.61 to 0.95; carbetocin: RR 0.70, 95% CI 0.38 to 1.28; misoprostol plus oxytocin: RR 0.90, 95% CI 0.72 to 1.14), and most secondary outcomes. Ergometrine plus oxytocin and misoprostol plus oxytocin had the poorest ranking for side effects. Carbetocin had a favourable side-effect profile, which was similar to oxytocin. However, the analysis was restricted to high-quality studies, carbetocin lost its ranking and was comparable to oxytocin. The relative cost-effectiveness of the alternative strategies is inconclusive, and the results are affected by both the uncertainty and inconsistency in the data reported on adverse events. For vaginal delivery, when assuming no adverse events, ergometrine plus oxytocin is less costly and more effective than all strategies except carbetocin. The strategy of carbetocin is both more effective and more costly than all other strategies. When taking adverse events into consideration, all prevention strategies, except oxytocin, are more costly and less effective than carbetocin. For delivery by caesarean section, with and without adverse events, the relative cost-effectiveness is different, again because of the uncertainty in the available data. Limitations: There was considerable uncertainty in findings within the planned subgroup analyses, and subgroup effects cannot be ruled out. Conclusions: Ergometrine plus oxytocin, carbetocin and misoprostol plus oxytocin are more effective uterotonic drug strategies for preventing PPH than the current standard, oxytocin. Ergometrine plus oxytocin and misoprostol plus oxytocin cause significant side effects. Carbetocin has a favourable side-effect profile, which was similar to oxytocin. However, most carbetocin trials are small and of poor quality. There is a need for a large high-quality trial comparing carbetocin with oxytocin; such a trial is currently being conducted by the WHO. The relative cost-effectiveness is inconclusive, and results are affected by uncertainty and inconsistency in adverse events data. Study registration: This study is registered as PROSPERO CRD42015020005; Cochrane Pregnancy and Childbirth Group (substudy) reference number 0871; PROSPERO–Cochrane (substudy) reference number CRD42015026568; and sponsor reference number ERN_13–1414 (University of Birmingham, Birmingham, UK). Funding: Funding for this study was provided by the National Institute for Health Research Health Technology Assessment programme in a research award to the University of Birmingham and supported by the UK charity Ammalife (UK-registered charity 1120236). The funders of the study had no role in study design, data collection, data synthesis, interpretation or writing of the report.

BackgroundHeatwaves 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 findingsWe 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.ConclusionsThis 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.

Summary: 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.