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Seok Woo Moon,1 Jee Wook Kim,2 Do Hoon Kim,3,4 Michael Adair,5 Daniel Oudin Åström,6 Elin Heldbo Reines,5 Minah Lee,7 Gayoung Kim7 1Department of Psychiatry and Research Institute of Medical Science, Konkuk University School of Medicine, Chungju, South Korea; 2Department of Neuropsychiatry, Hallym University Dongtan Sacred Heart Hospital, Dongtan, Korea; 3Department of Psychiatry, Hallym University Chuncheon Sacred Heart Hospital, Chuncheon, Korea; 4Mind-Neuromodulation Laboratory, College of Medicine, Hallym University, Chuncheon, Korea; 5Department of MSC Vortioxetine & Established Products, H. Lundbeck A/S, Valby, Denmark; 6Department of Real-World Evidence & Epidemiology, H. Lundbeck A/S, Valby, Denmark; 7Department of RA&MA, Lundbeck Korea Co., Ltd., Seoul, KoreaCorrespondence: Seok Woo Moon, Department of Psychiatry and Research Institute of Medical Science, Konkuk University School of Medicine, 82 Gugwon-daero, Chungju-si, Chungcheongbuk-do, 27376, South Korea, Tel +82-10-3276-1641, Email hessem@naver.comBackground: Patients with major depressive disorder (MDD) experience depressive symptoms such as anhedonia as well as cognitive dysfunction which can subsequently impair their work performance.Purpose: To assess the effectiveness and safety of vortioxetine in working patients with MDD in South Korea.Patients and Methods: This was a subgroup analysis of a prospective, multicenter, non-interventional, non-comparative post-marketing surveillance (PMS) study. Vortioxetine-naïve patients aged > 18 years who were administered with vortioxetine were followed for up to 24± 2 weeks. Working patients were defined as those who were working or studying full- (≥ 6 hours/day) or part-time (< 6 hours/day) at baseline. Effectiveness and adverse events (AEs), assessed by both clinician and patient-reported measured, were analyzed.Results: A total of 1082 working patients (mean age: 39.56 years) were included in the subgroup analysis. Clinically significant improvements in depressive symptoms, including anhedonia, were observed over the 24 weeks of follow-up, with mean scores for the total Montgomery-Asberg Depression Rating Scale (MADRS) and anhedonia subscale both significantly decreasing from baseline by mean±standard deviation (SD) of 9.73± 9.08 and 5.37± 5.24 points, respectively, at 24 weeks (both p< 0.001 vs baseline). The vast majority of patients (80.01%) treated with vortioxetine also showed improvements in mental health symptoms over the 24 weeks, measured using the Clinical Global Impression – Improvement (CGI-I) scores. Significant improvements in cognitive symptoms were also observed over the study period, measured by the Korean Version of the Perceived Deficits Questionnaire-Depression as well as Digit Symbol Substitution Test (all p< 0.0001 from baseline at Visits 2 and 3). Vortioxetine was well tolerated in working patients, with the respective rates of any AEs and serious AEs being 18.67% and 1.20%.Conclusion: Working patients treated with vortioxetine had improvements in their depressive symptoms (including anhedonia), cognitive function and performance. Vortioxetine was found to be well tolerated in this study.Keywords: major depressive disorder, non-interventional, post-marketing surveillance, South Korea, vortioxetine, work performance

Masaki Kato,1 Toshiaki Kikuchi,2 Koichiro Watanabe,3 Tomiki Sumiyoshi,4 Yoshiya Moriguchi,5 Daniel Oudin Åström,6 Michael Cronquist Christensen6 1Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan; 2Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; 3Department of Neuropsychiatry, Kyorin University School of Medicine, Tokyo, Japan; 4Department of Preventive Intervention for Psychiatric Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan; 5Lundbeck Japan K.K, Tokyo, Japan; 6H. Lundbeck A/S, Valby, DenmarkCorrespondence: Yoshiya Moriguchi, Medical Affairs, Lundbeck Japan, K.K, Kamiyacho Prime Place 8F, 4-1-17 Toranomon, Minato-ku, Tokyo, 105-0001, Japan, Email yomo@lundbeck.comPurpose: Originally developed in English, the Oxford Depression Questionnaire (ODQ) is a patient-reported scale specifically developed for assessing emotional blunting in people with major depressive disorder (MDD). We aimed to examine the reliability and validity of the Japanese version of the ODQ.Patients and methods: This was a prespecified analysis of a prospective, 24-week, multicenter, observational cohort study of employed Japanese outpatients with MDD initiating treatment with vortioxetine according to the Japanese label (JRCT1031210200). Participants were assessed using the Japanese version of the ODQ and other clinical rating scales at baseline and Weeks 8, 12 and 24.Results: One hundred and sixteen patients initiated vortioxetine and had ≥ 1 post-baseline visit. Directionally, the associations between ODQ scores and other clinical measures were as expected and demonstrated good concurrent validity. Factor analysis shows that the scale has a good fit for three factors. The Cronbach’s α coefficient was 0.912, and the scale also showed good test–retest reliability with intraclass correlation coefficients for the ODQ total score and domains ranging between 0.69 and 0.82. ODQ scores had strong positive correlations with symptom severity assessed using the Montgomery and Åsberg Depression Rating Scale and were moderately correlated with work productivity, overall functioning, and quality of life scales.Conclusion: Data from this prospective analysis confirm that the Japanese version of the ODQ retains the good validity and reliability of the original English scale and is suitable for use in prospective studies wanting to capture treatment effects on emotional blunting in MDD.Keywords: emotional blunting, major depressive disorder, Oxford depression questionnaire, MADRS-emotional blunting, validation, vortioxetine

Background: To assess whether retrograde cerebral perfusion reduces neurological injury and mortality in patients undergoing surgery for acute type A aortic dissection., Methods: Single-center, retrospective, observational study including all patients undergoing acute type A aortic dissection repair with deep hypothermic circulatory arrest between January 1998 and December 2022 with or without the adjunct of retrograde cerebral perfusion. 515 patients were included: 257 patients with hypothermic circulatory arrest only and 258 patients with hypothermic circulatory arrest and retrograde cerebral perfusion. The primary endpoints were clinical neurological injury, embolic lesions, and watershed lesions. Multivariable logistic regression was performed to identify independent predictors of the primary outcomes. Survival analysis was performed using Kaplan-Meier estimates., Results: Clinical neurological injury and embolic lesions were less frequent in patients with retrograde cerebral perfusion (20.2% vs. 28.4%, p = 0.041 and 13.7% vs. 23.4%, p = 0.010, respectively), but there was no significant difference in the occurrence of watershed lesions (3.0% vs. 6.1%, p = 0.156). However, after multivariable logistic regression, retrograde cerebral perfusion was associated with a significant reduction of clinical neurological injury (OR: 0.60; 95% CI 0.36-0.995, p = 0.049), embolic lesions (OR: 0.55; 95% CI 0.31-0.97, p = 0.041), and watershed lesions (OR: 0.25; 95%CI 0.07-0.80, p = 0.027). There was no significant difference in 30-day mortality (12.8% vs. 11.7%, p = ns) or long-term survival between groups., Conclusion: In this study, we showed that the addition of retrograde cerebral perfusion during hypothermic circulatory arrest in the setting of acute type A aortic dissection repair reduced the risk of clinical neurological injury, embolic lesions, and watershed lesions., (© 2024. The Author(s).)

In this study, the long-term mortality effects associated with exposure to PM 10 (particles with an aerodynamic diameter smaller than or equal to 10 µm), PM 2.5 (particles with an aerodynamic diameter smaller than or equal to 2.5 µm), BC (black carbon), and NO x (nitrogen oxides) were analyzed in a cohort in southern Sweden during the period from 1991 to 2016. Participants (those residing in Malmö, Sweden, born between 1923 and 1950) were randomly recruited from 1991 to 1996. At enrollment, 30,438 participants underwent a health screening, which consisted of questionnaires about lifestyle and diet, a clinical examination, and blood sampling. Mortality data were retrieved from the Swedish National Cause of Death Register. The modeled concentrations of PM 10 , PM 2.5 , BC, and NO x at the cohort participants' home addresses were used to assess air pollution exposure. Cox proportional hazard models were used to estimate the associations between long-term exposure to PM 10 , PM 2.5 , BC, and NO x and the time until death among the participants during the period from 1991 to 2016. The hazard ratios (HRs) associated with an interquartile range (IQR) increase in each air pollutant were calculated based on the exposure lag windows of the same year (lag0), 1-5 years (lag1-5), and 6-10 years (lag6-10). Three models were used with varying adjustments for possible confounders including both single-pollutant estimates and two-pollutant estimates. With adjustments for all covariates, the HRs for PM 10 , PM 2.5 , BC, and NO x in the single-pollutant models at lag1-5 were 1.06 (95% CI: 1.02-1.11), 1.01 (95% CI: 0.95-1.08), 1.07 (95% CI: 1.04-1.11), and 1.11 (95% CI: 1.07-1.16) per IQR increase, respectively. The HRs, in most cases, decreased with the inclusion of a larger number of covariates in the models. The most robust associations were shown for NO x , with statistically significant positive HRs in all the models. An overall conclusion is that road traffic-related pollutants had a significant association with mortality in the cohort.

Background: Clinical Impression of Severity Index for Parkinson's Disease (CISI-PD) is a simple tool that can easily be used in clinical practice. Few studies have investigated the relationship between health-related quality of life and the CISI-PD., Objective: To analyze the association of CISI-PD scores with those of generic (EQ-5D-5L) and Parkinson's disease (PD) disease-specific (Parkinson's Disease Questionnaire-8 [PDQ-8]) health-related quality of life assessments., Methods: Persons with idiopathic PD in the Swedish Parkinson's Disease registry with simultaneous registrations of CISI-PD and EQ-5D-5L and/or PDQ-8 were included. Correlations with EQ-5D dimensions were analyzed. The relationships between the CISI-PD, EQ-5D-5L, and PDQ-8 were estimated by linear mixed models with random intercept., Results: In the Swedish Parkinson's Disease registry, 3511 registrations, among 2168 persons, fulfilled the inclusion criteria. The dimensions self-care, mobility, and usual activities correlated moderately with the CISI-PD ( r s  = 0.60, r s  = 0.54, r s  = 0.57). Weak correlations were found for anxiety/depression and pain/discomfort ( r s  = 0.39, r s  = 0.29) ( P values < 0.001). The fitted model included the CISI-PD, age, sex, and time since diagnosis. The CISI-PD had a statistically significant impact on the EQ-5D and PDQ-8 ( P values < 0.001)., Conclusions: The CISI-PD provides a moderate correlation with the EQ-5D and could possibly be useful as a basis for defining health states in future health economic models and serving as outcomes in managed entry agreements. Nonetheless, the limitation of capturing nonmotor symptoms of the disease remains a shortcoming of clinical instruments, including the CISI-PD., (© 2022 International Parkinson and Movement Disorder Society.)

Dementia have substantial negative impact on the affected individual, their care partners and society. Persons living with Parkinson's disease (PwP) are also to a large extent living with dementia. The aim of this study is to estimate time to dementia in PD using data from a large quality register with access to baseline clinical and patient reported data merged with Swedish national health registries. Persons with Parkinson's disease in the Swedish Neuro Registries/Parkinson's Disease Swedish PD Registry (PARKreg) in Sweden were included and linked to national health registries and matched by sex and age to controls without PD. Time to dementia was analysed with Cox regression models assuming proportional hazards, with time since diagnosis as the underlying time variable. In this large prospective cohort study, PwP had approximately four times higher risk of developing dementia as compared to age and sex-matched controls, a finding which remained after adjusting for potential confounders. The present results underline the high risk of dementia in PD and further emphasize the importance of developing symptomatic and ultimately disease modifying strategies to counteract this part of the non-motor symptomatology in PD., (© 2022. The Author(s).)

Despite the increasing number of studies on industrially contaminated sites (ICS) and their health effects, there are very few studies on perinatal health outcomes in ICSs. In the present study, we examined the perinatal health inequalities by comparing adverse birth outcomes (ABOs) in the oil shale industry region of Ida-Viru County in Estonia with national-level figures and investigated the effects of maternal environmental and sociodemographic factors. Based on the 208,313 birth records from 2004-2018, Ida-Viru ICS has a birth weight 124.5 g lower than the average of 3544 g in Estonia. A higher prevalence of preterm birth (4.3%) and low birth weight (4.8%) in Ida-Viru ICS is found compared to 3.3% on both indicators at the national level. Multiple logistic regression analysis shows the statistically significant association of ABOs with fine particle (PM 2.5 ) air pollution, mother's ethnicity, and education throughout Estonia. However, in Ida-Viru ICS, the ABOs odds are remarkably higher in these characteristics except for the mother's ethnicity. Furthermore, the ABOs are associated with the residential proximity to ICS. Thus, the Ida-Viru ICS has unequally higher odds of adverse perinatal health across the environmental and sociodemographic factors. In addition to reducing the air pollutants, policy actions on social disparities are vital to address the country's unjustly higher perinatal health inequalities, especially in the Ida-Viru ICS.

While prenatal exposure to ambient air pollution has been shown to be associated with reduced birth weight, there is substantial heterogeneity across studies, and few epidemiological studies have utilized source-specific exposure data. The aim of the present study was, therefore, to investigate the associations between local, source-specific exposure to fine particulate matter (PM2.5) during pregnancy and birth weight. An administrative cohort comprising 40,245 singleton births from 2000 to 2009 in Scania, Sweden, was combined with data on relevant covariates. Investigated sources of PM2.5 included all local sources together as well as tailpipe exhaust, vehicle wear-and-tear, and small-scale residential heating separately. The relationships between these exposures, represented as interquartile range (IQR) increases, and birth weight (continuous) and low birth weight (LBW; <2500 g) were analyzed in crude and adjusted models. Each local PM2.5 source investigated was associated with reduced birth weight; average decreases varied by source (12−34 g). Only small-scale residential heating was clearly associated with LBW (adjusted odds ratio: 1.14 (95% confidence interval: 1.04−1.26) per IQR increase). These results add to existing evidence that prenatal exposure to ambient air pollution disrupts fetal growth and suggest that PM2.5 from both vehicles and small-scale residential heating may reduce birth weight.

Background: Ambient particulate matter is a leading risk factor for disease globally. Particulate matter 10 (PM 10 ) and particulate matter 2.5 (PM 2.5 ) are derived from different sources, including operating motor vehicles as well as from industrial activities. In this study we investigate the association between increased concentrations of PM and total daily visits to the psychiatric emergency unit (PEV). Further, the aim is to identify specific risk groups who are more susceptible to the effects of air pollution exposure by studying sex, age, ongoing psychiatric follow-up and diagnoses of depression/anxiety or substance use., Material and Methods: The sample was comprised of data from 2740 days to 81 548 PEVs at Sahlgrenska University Hospital in Gothenburg and daily mean concentrations of PM 10 and PM 2.5 . A time-stratified case-crossover design was used to analyse associations between air pollution and PEVs., Results: Mean number of daily PEVs were 35 and sex distribution was even. PM exposure was associated with total PEV at lag 0 (the same day), by RR 1.016 (95% confidence interval [CI] 1.004-1.028) and RR 1.020 (95%CI 1.003-1.038) per 10 μg/m 3 increase in PM 10 and PM 2.5 , respectively. In females, PEV were increased at lag 0 and lag 1, and in males at lag 1 and lag 2. In the age-stratified analysis, PEVs significantly increased following PM exposure amongst individuals aged 35-65 years by lag 0-2 and in individuals who had contact with outpatient care at lag 0 to lag 1. There were no associations between air pollution and PEVs for any specific diagnostic group evaluated (amongst depression, anxiety and substance use disorder)., Conclusions: The results indicate that acute exposure to PM 10 and PM 2.5 may trigger acute worsening in mental health in both males and females, especially among 35-65 year old individuals. However, in subgroups of the most common psychiatric diagnoses, we did not observe statistically significant associations with PM exposure., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Alzheimer's disease (AD) and other dementias currently represent the fifth most common cause of death in the world, according to the World Health Organization, with a projected future increase as the proportion of the elderly in the population is growing. Air pollution has emerged as a plausible risk factor for AD, but studies estimating dementia cases attributable to exposure to fine particulate matter (PM 2.5 ) air pollution and resulting monetary estimates are lacking., Methods: We used data on average population-weighted exposure to ambient PM 2.5 for the entire population of Sweden above 30 years of age. To estimate the annual number of dementia cases attributable to air pollution in the Swedish population above 60 years of age, we used the latest concentration response functions (CRF) between PM 2.5 exposure and dementia incidence, based on ten longitudinal cohort studies, for the population above 60 years of age. To estimate the monetary burden of attributable cases, we calculated total costs related to dementia, including direct and indirect lifetime costs and intangible costs by including quality-adjusted life years (QALYs) lost. Two different monetary valuations of QALYs in Sweden were used to estimate the monetary value of reduced quality-of-life from two different payer perspectives., Results: The annual number of dementia cases attributable to PM 2.5 exposure was estimated to be 820, which represents 5% of the annual dementia cases in Sweden. Direct and indirect lifetime average cost per dementia case was estimated to correspond € 213,000. A reduction of PM 2.5 by 1 μg/m 3 was estimated to yield 101 fewer cases of dementia incidences annually, resulting in an estimated monetary benefit ranging up to 0.01% of the Swedish GDP in 2019., Conclusion: This study estimated that 5% of annual dementia cases could be attributed to PM 2.5 exposure, and that the resulting monetary burden is substantial. These findings suggest the need to consider airborne toxic pollutants associated with dementia incidence in public health policy decisions.

Background: There is strong experimental evidence that physiologic stress from high temperatures is greater if humidity is higher. However, heat indices developed to allow for this have not consistently predicted mortality better than dry-bulb temperature., Objectives: We aimed to clarify the potential contribution of humidity an addition to temperature in predicting daily mortality in summer by using a large multicountry dataset., Methods: In 445 cities in 24 countries, we fit a time-series regression model for summer mortality with a distributed lag nonlinear model (DLNM) for temperature (up to lag 3) and supplemented this with a range of terms for relative humidity (RH) and its interaction with temperature. City-specific associations were summarized using meta-analytic techniques., Results: Adding a linear term for RH to the temperature term improved fit slightly, with an increase of 23% in RH (the 99th percentile anomaly) associated with a 1.1% [95% confidence interval (CI): 0.8, 1.3] decrease in mortality. Allowing curvature in the RH term or adding terms for interaction of RH with temperature did not improve the model fit. The humidity-related decreased risk was made up of a positive coefficient at lag 0 outweighed by negative coefficients at lags of 1-3 d. Key results were broadly robust to small model changes and replacing RH with absolute measures of humidity. Replacing temperature with apparent temperature, a metric combining humidity and temperature, reduced goodness of fit slightly., Discussion: The absence of a positive association of humidity with mortality in summer in this large multinational study is counter to expectations from physiologic studies, though consistent with previous epidemiologic studies finding little evidence for improved prediction by heat indices. The result that there was a small negative average association of humidity with mortality should be interpreted cautiously; the lag structure has unclear interpretation and suggests the need for future work to clarify. https://doi.org/10.1289/EHP5430.

Background and objectives: Despite global warming, the climate in Northern Europe is generally cold, and the large number of deaths due to non-optimal temperatures is likely due to cold temperatures. The aim of the current study is to investigate the association between cold temperatures and all-cause mortality, as well as cause-specific mortality, in Tallinn and Riga in North-Eastern Europe. Materials and Methods: We used daily information on deaths from state death registries and minimum temperatures from November to March over the period 1997-2015 in Tallinn and 2009-2015 in Riga. The relationship between the daily minimum temperature and mortality was investigated using the Poisson regression, combined with a distributed lag non-linear model considering lag times of up to 21 days. Results: We found significantly higher all-cause mortality owing to cold temperatures both in Tallinn (Relative Risk (RR) = 1.28, 95% Confidence Interval (CI) 1.01-1.62) and in Riga (RR = 1.41, 95% CI 1.11-1.79). In addition, significantly increased mortality due to cold temperatures was observed in the 75+ age group (RR = 1.64, 95% CI 1.17-2.31) and in cardiovascular mortality (RR = 1.83, 95% CI 1.31-2.55) in Tallinn and in the under 75 age group in Riga (RR = 1.58, 95% CI 1.12-2.22). In this study, we found no statistically significant relationship between mortality due to respiratory or external causes and cold days. The cold-related attributable fraction (AF) was 7.4% (95% CI -3.7-17.5) in Tallinn and 8.3% (95% CI -0.5-16.3) in Riga. This indicates that a relatively large proportion of deaths in cold periods can be related to cold in North-Eastern Europe, where winters are relatively harsh.

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., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: MLB has received research grants from NIH and EPA, and travel expenses paid by universities and research institutions in order to give seminars and participate in research meetings. All other authors have declared that no competing interests exist.

Background: Air pollution is one of the leading causes of mortality and morbidity worldwide. Experimental studies, and a few epidemiological studies, suggest that air pollution may cause acute exacerbation of psychiatric disorders, and even increase the rate of suicide attempts, but epidemiological studies on air pollution in association with psychiatric disorders are still few. Our aim was to investigate associations between daily fluctuations in air pollution concentrations and the daily number of visits to a psychiatric emergency unit., Methods: Data from Sahlgrenska University Hospital, Gothenburg, Sweden, on the daily number of visits to the Psychiatric emergency unit were combined with daily data on monitored concentrations of respirable particulate matter(PM 10 ), ozone(O 3 ), nitrogen dioxides(NO 2 ) and temperature between 1st July 2012 and 31st December 2016. We used a case-crossover design to analyze data with conditional Poisson regression models allowing for over-dispersion. We stratified data on season., Results: Visits increased with increasing PM 10 levels during the warmer season (April to September) in both single-pollutant and two-pollutant models. For example, an increase of 3.6% (95% Confidence Interval, CI, 0.4-7.0%) was observed with a 10 μg/m3 increase in PM 10 adjusted for NO 2 . In the three-pollutant models (adjusting for NO 2 and O 3 simultaneously) the increase was 3.3% (95% CI, -0.2-6.9). There were no clear associations between the outcome and NO 2 , O 3 , or PM 10 during the colder season (October to March)., Conclusions: Ambient air particle concentrations were associated with the number of visits to the Psychiatric emergency unit in the warm season. The results were only borderline statistically significant in the fully adjusted (three-pollutant) models in this small study. The observation could be interpreted as indicative of air pollution as either exacerbating an underlying psychiatric disorder, or increasing mental distress, even in areas with comparatively low levels of air pollution. In combination with the severe impact of psychiatric disorders and mental distress on society and individuals, our results are a strong warrant for future research in this area.

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.

The health burden from heatwaves is expected to increase with rising global mean temperatures and more extreme heat events over the coming decades. Health-related effects from extreme heat are more common in elderly populations. The population of Europe is rapidly aging, which will increase the health effects of future temperatures. In this study, we estimate the magnitude of adaptation needed to lower vulnerability to heat in order to prevent an increase in heat-related deaths in the 2050s; this is the Adaptive Risk Reduction (ARR) needed. Temperature projections under Representative Concentration Pathway (RCP) 4.5 and RCP 8.5 from 18 climate models were coupled with gridded population data and exposure-response relationships from a European multi-city study on heat-related mortality. In the 2050s, the ARR for the general population is 53.5%, based on temperature projections under RCP 4.5. For the population above 65 years in Southern Europe, the ARR is projected to be 45.9% in a future with an unchanged climate and 74.7% with climate change under RCP 4.5. The ARRs were higher under RCP 8.5. Whichever emission scenario is followed or population projection assumed, Europe will need to adapt to a great degree to maintain heat-related mortality at present levels, which are themselves unacceptably high, posing an even greater challenge.

The relationship between temperature and mortality is well established but has seldom been investigated in terms of external causes. In some Eastern European countries, external cause mortality is substantial. Deaths owing to external causes are the third largest cause of mortality in Estonia, after cardiovascular disease and cancer. Death rates owing to external causes may reflect behavioural changes among a population. The aim for the current study was to investigate if there is any association between temperature and external cause mortality, in Estonia. We collected daily information on deaths from external causes (ICD-10 diagnosis codes V00-Y99) and maximum temperatures over the period 1997-2013. The relationship between daily maximum temperature and mortality was investigated using Poisson regression, combined with a distributed lag non-linear model considering lag times of up to 10 days. We found significantly higher mortality owing to external causes on hot (the same and previous day) and cold days (with a lag of 1-3 days). The cumulative relative risks for heat (an increase in temperature from the 75th to 99th percentile) were 1.24 (95% confidence interval, 1.14-1.34) and for cold (a decrease from the 25th to 1st percentile) 1.19 (1.03-1.38). Deaths due to external causes might reflect changes in behaviour among a population during periods of extreme hot and cold temperatures and should therefore be investigated further, because such deaths have a severe impact on public health, especially in Eastern Europe where external mortality rates are high.

Background and Aims: Asthma is one of the most common respiratory diseases in the world. Research has shown that temporal increases in air pollution concentrations can aggravate asthma symptoms. The aim of this study was to assess whether individuals living in areas with higher air pollution concentrations responded differently to short-term temporal exposure to air pollution than those living in lower air pollution areas., Method: The study was designed as a case-crossover study in Scania, Sweden. Outcome data was visits to primary health care clinics with asthma as the main complaint during the years 2007 to 2010. Nitrogen dioxide levels were obtained from 21 different air pollution monitoring stations. Short-term exposure was defined as the average concentration four days prior to the visit. Data was pooled for areas above and below a two-year average NO2 concentration of 10 μg/m3, dispersion modelled with an emission database., Results: The short-term association between NO2 and asthma visits seemed stronger in areas with NO2 levels below 10 μg/m3, with an odds ratio (OR) of 1.15 (95% confidence interval (CI): 1.08-1.23) associated with a 10 μg/m3 increase in NO2 compared to areas above 10 μg/m3 NO2 levels, where corresponding OR of 1.09 (95% CI: 1.02-1.17). However, this difference was not statistically significant. (p = 0.13)., Conclusions: The study provided some evidence, although not statistically significant, that short-term associations between air pollution and asthma may depend on background air pollution levels. However, we cannot rule out that the association is due to other spatially dependent factors in Scania. The study should be reproduced in other study areas., Competing Interests: The authors have declared that no competing interests exist.

Objective: To investigate associations between exposure to air pollution and child and adolescent mental health., Design: Observational study., Setting: Swedish National Register data on dispensed medications for a broad range of psychiatric disorders, including sedative medications, sleeping pills and antipsychotic medications, together with socioeconomic and demographic data and a national land use regression model for air pollution concentrations for NO2, PM10 and PM2.5., Participants: The entire population under 18 years of age in 4 major counties. We excluded cohort members whose parents had dispensed a medication in the same medication group since the start date of the register. The cohort size was 552 221., Main Outcome Measures: Cox proportional hazards models to estimate HRs and their 95% CIs for the outcomes, adjusted for individual-level and group-level characteristics., Results: The average length of follow-up was 3.5 years, with an average number of events per 1000 cohort members of ∼21. The mean annual level of NO2 was 9.8 µg/m(3). Children and adolescents living in areas with higher air pollution concentrations were more likely to have a dispensed medication for a psychiatric disorder during follow-up (HR=1.09, 95% CI 1.06 to 1.12, associated with a 10 µg/m(3) increase in NO2). The association with NO2 was clearly present in 3 out of 4 counties in the study area; however, no statistically significant heterogeneity was detected., Conclusion: There may be a link between exposure to air pollution and dispensed medications for certain psychiatric disorders in children and adolescents even at the relatively low levels of air pollution in the study regions. The findings should be corroborated by others., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: The mortality impacts of hot and cold temperatures have been thoroughly documented, with most locations reporting a U-shaped relationship with a minimum mortality temperature (MMT) at which mortality is lowest. How MMT may have evolved over previous decades as the global mean surface temperature has increased has not been thoroughly explored., Objective: We used observations of daily mean temperatures to investigate whether MMT changed in Stockholm, Sweden, from the beginning of the 20th century until 2009., Methods: Daily mortality and temperature data for the period 1901-2009 in Stockholm, Sweden, were used to model the temperature-mortality relationship. We estimated MMT using distributed lag nonlinear Poisson regression models considering lags up to 21 days of daily mean temperature as the exposure variable. To avoid large influences on the MMT from intra- and interannual climatic variability, we estimated MMT based on 30-year periods. Furthermore, we investigated whether there were trends in the absolute value of the MMT and in the relative value of the MMT (the corresponding percentile of the same-day temperature distribution) over the study period., Results: Our findings suggest that both the absolute MMT and the relative MMT increased in Stockholm, Sweden, over the course of the 20th century., Conclusions: The increase in the MMT over the course of the 20th century suggests autonomous adaptation within the context of the large epidemiological, demographical, and societal changes that occurred. Whether the rate of increase will be sustained with climate change is an open question., Citation: Oudin Åström D, Tornevi A, Ebi KL, Rocklöv J, Forsberg B. 2016. Evolution of minimum mortality temperature in Stockholm, Sweden, 1901-2009. Environ Health Perspect 124:740-744; http://dx.doi.org/10.1289/ehp.1509692.