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

The report “Effects of Air Temperature Modified by Vulnerability Factors” was prepared as a milestone by researchers in the EU Project EXHAUSTION*. This report summarises the evidence on the interactive effects of high air temperature and various vulnerability factors, including the environmental, socio-economic, and individual behavioral factors on heart- and lung-related deaths and diseases (cardiopulmonary mortality and morbidity) across Europe. The study was conducted at the city, small-area (e.g., municipalities), and individual level. The findings show a greater vulnerability to heat for people living in urban areas with dense population, high air pollution levels, low coverage of green spaces, as well as areas with low Gross Domestic Product. Moreover, people with chronic pre-existing diseases and the elderly were found to be at greater risk. The findings highlight the urgent need to improve the urban environment as well as the health status and living conditions in European cities to contrast the impacts of heat and future climate change. This report alerts stakeholders and policymakers that targeted climate change adaptation measures need to be considered to protect vulnerable population and thereby increase European resilience to climate change.

Background Although the associations of outdoor air pollution exposure with mortality and hospital admissions are well established, few previous studies have reported on primary care clinical and prescribing data. We assessed the associations of short and long-term pollutant exposures with General Practitioner respiratory consultations and inhaler prescriptions. Methods Daily primary care data, for 2009–2013, were obtained from Lambeth DataNet (LDN), an anonymised dataset containing coded data from all patients (1.2 million) registered at general practices in Lambeth, an inner-city south London borough. Counts of respiratory consultations and inhaler prescriptions by day and Lower Super Output Area (LSOA) of residence were constructed. We developed models for predicting daily PM2.5, PM10, NO2 and O3 per LSOA. We used spatio-temporal mixed effects zero inflated negative binomial models to investigate the simultaneous short- and long-term effects of exposure to pollutants on the number of events. Results The mean concentrations of NO2, PM10, PM2.5 and O3 over the study period were 50.7, 21.2, 15.6, and 49.9 μg/m3 respectively, with all pollutants except NO2 having much larger temporal rather than spatial variability. Following short-term exposure increases to PM10, NO2 and PM2.5 the number of consultations and inhaler prescriptions were found to increase, especially for PM10 exposure in children which was associated with increases in daily respiratory consultations of 3.4% and inhaler prescriptions of 0.8%, per PM10 interquartile range (IQR) increase. Associations further increased after adjustment for weekly average exposures, rising to 6.1 and 1.2%, respectively, for weekly average PM10 exposure. In contrast, a short-term increase in O3 exposure was associated with decreased number of respiratory consultations. No association was found between long-term exposures to PM10, PM2.5 and NO2 and number of respiratory consultations. Long-term exposure to NO2 was associated with an increase (8%) in preventer inhaler prescriptions only. Conclusions We found increases in the daily number of GP respiratory consultations and inhaler prescriptions following short-term increases in exposure to NO2, PM10 and PM2.5. These associations are more pronounced in children and persist for at least a week. The association with long term exposure to NO2 and preventer inhaler prescriptions indicates likely increased chronic respiratory morbidity.

Land use regression (LUR) and dispersion/chemical transport models (D/CTMs) are frequently applied to predict exposure to air pollution concentrations at a fine scale for use in epidemiological studies. Moreover, the use of satellite aerosol optical depth data has been a key predictor especially for particulate matter pollution and when studying large populations. Within the STEAM project we present a hybrid spatio-temporal modeling framework by (a) incorporating predictions from dispersion modeling of nitrogen dioxide (NO2), ozone (O3) and particulate matter with an aerodynamic diameter equal or less than 10 μm (PM10) and less than 2.5 μm (PM2.5) into a spatio-temporal LUR model; and (b) combining the predictions LUR and dispersion modeling and additionally, only for PM2.5, from an ensemble machine learning approach using a generalized additive model (GAM). We used air pollution measurements from 2009 to 2013 from 62 fixed monitoring sites for O3, 115 for particles and up to 130 for NO2, obtained from the dense network in the Greater London Area, UK. We assessed all models following a 10-fold cross validation (10-fold CV) procedure. The hybrid models performed better compared to separate LUR models. Incorporation of the dispersion estimates in the LUR models as a predictor, improved the LUR model fit: CV-R2 increased to 0.76 from 0.71 for NO2, to 0.79 from 0.57 for PM10, to 0.81 to 0.66 for PM2.5 and to 0.75 from 0.62 for O3. The CV-R2 obtained from the hybrid GAM framework was also increased compared to separate LUR models (CV-R2 = 0.80 for NO2, 0.76 for PM10, 0.79 for PM2.5 and 0.75 for O3). Our study supports the combined use of different air pollution exposure assessment methods in a single modeling framework to improve the accuracy of spatio-temporal predictions for subsequent use in epidemiological studies.

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

The report “Effects of air Temperature on Cardiopulmonary Mortality and Morbidity in Europe” was prepared as a milestone of the EU Project EXHAUSTION. It summarizes the evidence on the effects of different levels and changes in ambient air temperature on cardiopulmonary (CPD) mortality and morbidity across Europe and puts a spotlight on the vulnerable and susceptible population. It can help stakeholders and policymakers to plan adaptation measures to protect the vulnerable and susceptible population and increase European resilience towards climate change and extreme weather events.

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

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

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

The adverse health effects of air pollutants, especially those of PM 2.5, are well documented. However, a lack of adequate monitoring and weaknesses in modelling approaches do not allow a good assessment of health effects in many areas of the World. Advances in computational methods and the availability of new data sets, e.g. satellite remote observations, have enlarged the possibilities of modelling for application in large scale health effects studies. However, PM 2.5 monitoring is very recent in most of the World and more limited compared to other pollutants, and understanding how to use PM 10 monitors to estimate PM 2.5 exposure is therefore important. Since interest in these methods is relatively recent, there is a need for testing their performance against ambient measurements, but long term PM 2.5 datasets are less readily available than PM 10 in many regions. In the present study we report the methodology and results of using regression modelling and a machine learning method (Random Forest-RF), as well as a combination of the two, to enhance a PM 2.5 measurement data base in London using PM 10 and NO x measurements as well as other predictors and compare the relative performance of each method. We found that the combination of predictions by the regression model and the RF performs best and we obtain a cross-validation R 2 of 99.29% and 98.22% for the 5-year periods 2004–2008 and 2009–2013, respectively, and a Mean Square Error near 1. Our enhanced data base for PM 2.5 is available for use by other researchers.

BACKGROUND/AIM Insulin-like growth factor-I (IGF-I) regulates various aspects of cancer biology. There is a growing body of evidence regarding the potential distinct role of IGF-I isoforms, particularly of IGF-IEc, in the pathophysiology of various human cancer types, however, there are no studies which examined the expression of the different IGF-I isoforms in renal cell carcinoma (RCC). This study aimed to characterize the expression of IGF-IEc in human RCC tissues and investigated whether its expression is associated with the histopathological type of RCC as well as with the overall survival of patients. MATERIALS AND METHODS Formalin-fixed paraffin-embedded renal tissue samples from 94 patients (58 males and 36 females) were assessed for IGF-IEc expression by immunohistochemistry. RESULTS RCC tissues showed mainly cytoplasmic IGF-IEc staining but immunoreactivity of IGF-IEc was also localized in the cell membrane. Significantly lower IGF-IEc expression was found in clear cell RCC vs. all other histological types (p=0.010), and this remained significant after adjusting for tumor size, grade, stage, and mitotic index (p

Although the health effects of short-term exposure to ambient particles have been well documented, there is a need to update scientific knowledge due to the continuously changing profile of the air pollution mixture. Furthermore the effect of the severe economic crisis in Greece that started in 2008 on previously reported associations has not been studied. We assessed the change in mortality risk associated with short-term exposure to PM10 in Athens, Greece during 2001–12.Time-series data on the daily concentrations of regulated particles and all cause, cardiovascular and respiratory mortality were analyzed using overdispersed Poisson regression models, controlling for time-varying confounders such as seasonality, meteorology, influenza outbreaks, summer holidays and day of the week. We assessed changes in risk over time by inclusion of an interaction term between particles' levels and time or predefined periods, i.e. 2001–07 and 2008–12.While the related mortality risks increased over the analyzed period, the difference before and after 2008 was significant only for total mortality (p-value for interaction .03) and driven by the difference observed among those ≥75 years. An interquartile increase in PM10 before 2008 was associated with 1.51% increase in deaths among ≥75 years (95% Confidence interval (CI): 0.62%, 2.40%), while after 2008 with a 2.61% increase (95%CI: 1.72%, 3.51%) (p-value for interaction .01).Our results indicate that despite the decline in particles' concentration in Athens, Greece during 2001–12 the associated mortality risk has possibly increased, suggesting that the economic crisis initiated in 2008 may have led to changes in the particles' composition due to the ageing of the vehicular fleet and the increase in the use of biomass fuel for heating. Keywords: Air pollution, Mortality risk, Particulate matter, Short-term effects, Trends

Abstract The health effects of acute exposure to temperature extremes are established; those of long-term exposure only recently received attention. We performed a systematic review to assess the associations of long-term (>3 months) exposure to higher or lower temperature on total and cardiopulmonary mortality and morbidity, screening 3455 studies and selecting 34. The studies were classified in those observing associations within a population over years with changing annual temperature indices and those comparing areas with a different climate. We also assessed the risk of bias, adapting appropriately an instrument developed by the World Health Organization for air pollution. Studies reported that annual temperature indices for extremes and variability were associated with annual increases in mortality, indicating that effects of temperature extremes cannot be attributed only to short-term mortality displacement. Studies on cardiovascular mortality indicated stronger associations with cold rather than hot temperature, whilst those on respiratory outcomes reported effects of both heat and cold but were few and used diverse health outcomes. Interactions with air pollution were not generally assessed. The few studies investigating effect modification showed stronger effects among the elderly and those socially deprived. Comparisons of health outcome prevalence between areas reported lower blood pressure and a tendency for higher obesity in populations living in warmer climates. Our review indicated interesting associations between long-term exposure to unusual temperature levels in specific areas and differences in health outcomes and cardiovascular risk factors between geographical locations with different climate, but the number of studies by design and health outcome was small. Risk of bias was identified because of the use of crude exposure assessment and inadequate adjustment for confounding. More and better designed studies, including the investigation of effect modifiers, are needed.

Elevated urban temperatures and heatwaves are a serious threat to the health and wellbeing of the continuously growing urban population and are projected to worsen under climate change. For this reason well-informed disaster risk reduction (DRR) actions, where science and technology play a key role, are required. However insufficient communication between scientific and policy-making communities (known as the science-policy gap) hampers the use of science in DRR. Hence there is a strong need to interpret existing scientific knowledge into actionable knowledge, i.e. science that is useful, usable and used. This article presents a series of services and tools that build-upon existing scientific knowledge and aim to provide actionable knowledge to authorities and citizens for reducing the risks of elevated urban temperatures. The above were implemented in the context of the European Commission’s Thermal Risk rEduction Actions and tools for secURE cities (TREASURE) project, and address many of the goals and priorities for action set in the Sendai framework for disaster risk reduction (SFDRR) of the United Nations. A key policy-making user of the implemented services and tools is the City of Athens in Greece, which is one of the largest metropolitan areas in Europe.

Background Inconsistent and contradictory findings have appeared in the literature concerning the impact of body position on oxygenation in pleural effusion. Methods We attempted to elucidate whether the size of the pleural effusion in patients with no parenchymal disease is the main determinant of posture-induced alterations in oxygenation parameters. We studied 62 spontaneously breathing patients aged 65.3±7.8 years (mean±SD), of whom 36 had large and massive-sized effusions (Group A) and 26 had small and moderate-sized effusions (Group B). Arterial blood gases were determined in four different body positions: sitting (SIT), supine (SUP), ipsilateral (IPS) and contralateral (CON) to the effusion side, after remaining relaxed for at least 20 min in each position. Separation into groups A and B was deliberately set from the position of the fluid meniscus line on a posteroanterior chest film just above the upper costal margin of the sixth anterior rib. A two-way ANOVA model with outcome variables PaO2, PaCO2 and [A–a] DO2 was used. Results In both groups the best oxygenation was found in SIT. The worst oxygenation (highest [A–a] DO2 value) occurred in group A in CON compared with IPS (59.4±7.6 vs 49.0±7.5 mm Hg, p Conclusions Patients with large-sized effusions exhibit the worst oxygenation when lying on the side contralateral to the effusion, while those with small-sized effusions exhibit the worst oxygenation when lying on the side ipsilateral to the effusion.

Background Several studies investigated the effects of thoracocentesis on aspects of respiratory function without generally ensuring absence of coexistent lung pathology or homogeneity in initial size of the effusion. Methods We studied 90 patients aged 61.6±15.9 years (mean±SD) separated into a group A with small-sized or medium-sized effusion (A=56 patients) and a group B with large and massive one (B=34 patients). There was no significant lung lesion or cardiovascular pathology. The basic spirometric parameters and maximal respiratory pressures were recorded on three instances: just before thoracocentesis (T1), 30 min after completion of the procedure (T2) and after 48 hours (T3). Results At T2 vs T1, groups A and B respectively presented significant change (mean±SD) (increase) in forced vital capacity (FVC) of 0.071±0.232 and 0.139±0.224 L, in forced expiratory volume in 1 s (FEV1) of 0.127±0.231 and 0.201±0.192 L, in FEV1/FVC of 2.8% and 4.9%, in peak expiratory flow rate (PEFR) of 0.342±0.482 and 0.383±0.425 L/s, in maximal expiratory pressure (MEP) of 0.049±0.037 and 0.049±0.039 kPa and in maximal inspiratory pressure (MIP) of 0.040±0.041 kPa only in group A while decrease in MIP with significant change of 0.055±0.051 kPa in group B. At T3 vs T2 in groups A and B, there was significant change (decrease) in FEV1/FVC of 2.7% and 4.6% as well as significant change (increase) in MIP of 0.036±0.046 and 0.115±0.060 and in MEP of 0.049±0.043 and 0.070±0.048 kPa. Conclusions Thoracocentesis is associated with progressive-small relative to the volume of fluid removed-increases in lung volumes. In larger effusions at T2, a transient decrease in MIP is observed presumably due to temporary geometric distortion of the diaphragm immediately after fluid removal.

Introduction Acute aortic dissection (AAD) represents surgical emergency and current literature mainly consists of postoperative outcome reports. Long term outcome and quality of life have not extensively been investigated. Purpose This is a single center study to assess long term outcome and quality of life of patients who underwent emergency surgery for AAD. Methods From January 2007 until December 2009, 74 consecutive patients were operated for AAD type A in our hospital. Seventeen died during hospital stay and 12 died during follow-up. Mean follow up was 108±10 months. Seventeen patients refused to answer the SF-36 questionnaire; therefore our study group consists of 28 patients. The SF-36 Questionnaire was retrospectively obtained by phone calls, the first, fifth and tenth postoperative year and 2 summary scores are reported, physical (PCS) and mental (MCS). Results Our in-hospital mortality was 23%, late mortality 21.1% and the overall mortality was 39.2%. Significant differences in both physical and mental score over time were found among the 28 long-term survivors (Table). Both PCS and MCS at 1st, 5th and 10th year did not differ compared to age-matched general population but compared to subjects with one or more chronic diseases both PCS and MCS were both significantly better at 5yrs in our patients vs controls (p=0.0028 and p=0.0259, respectively). Likewise, at 5 years PCS but not MCS was better in comparison to subjects with a history of one hospitalization the preceding year (p=0.035 and p=0.1, respectively). Descriptive statistics of physical and mental component summary score over time Score 1 year (FU1) 5 years (FU2) 10 years (FU3) p-value Mean (SD) Mean (SD) Mean (SD) PCS 45.4 (7.7) 50.3 (7.0) 46.8 (9.2) 0.008* MCS 42.8 (15.1) 49.7 (12.7) 49.1 (12.3) 0.001** PCS, Physical component summary; *1 vs 5: p=0.003, 1 vs 10: p=0.469, 5 vs 10: p=0.027. MCS, Mental component summary; **1 vs 5: p=0.001, 1 vs 10: p=0.001, 5 vs 10: p=0.939. SD, standard deviation. Conclusion Quality of life improves after the 1st post-operative year and is comparable to healthy subjects. Although acute dissection is a catastrophic event with high mortality despite successful and timely repair, long term survival and quality of life on the long term are favorable.

Spatial variability in temperature exists within metropolitan areas but very few studies have investigated intra-urban differentiation in the temperature-mortality effects. We investigated whether local characteristics of 42 Municipalities within the Greater Athens Area lead to modified temperature effects on mortality and if effect modifiers can be identified. Generalized Estimating Equations models were used to assess the effect of high ambient temperature on the total and cause-specific daily number of deaths and meta-regression to investigate effect modification. We found significant effects of daily temperature increases on all-cause, cardiovascular, and respiratory mortality (e.g., for all ages 4.16% (95% CI: 3.73,4.60%) per 1 &deg, C increase in daily temperature (lags 0&ndash, 3). Heterogeneity in the effect estimates between Municipalities was observed in several outcomes and environmental and socio-economic effect modifying variables were identified, such as % area coverage of buildings, length of roads/km2, population density, % unemployed, % born outside the EU countries and mean daily temperature. To further examine the role of temperature, we alternatively used modelled temperature per Municipality and calculated the effects. We found that heterogeneity was reduced but not eliminated. It appears that there are socioeconomic status and environmental determinants of the magnitude of heat-related effects on mortality, which are detected with some consistency and should be further investigated.

ObjectiveTo study trends of infant mortality rate (IMR) and neonatal mortality rate in Greece during the period 2004–2016 and explore the role of sociodemographic factors in the years of crisis.DesignNationwide individual data for live births and infant (0–11 months) deaths provided by the Hellenic Statistical Authority were examined using Poisson, joinpoint regression and interrupted time series (ITS) analyses.SettingGreece.ParticipantsAll infant deaths (n=4862) over the 13-year period, of which 87.2% were born to Greek mothers, and respective live births.Main outcome measuresEvolution of IMR (0–364 days), early (ResultsBy Poisson regression, overall, during the study period, among infants of Greek mothers, IMR and PNMR declined significantly (−0.9%; 95% CI −1.7% to −0.1% and −1.6%; −3.0% to −0.2% annually, respectively), although differentially by place of residence (IMRurban: −2.1%; −2.9% to −1.3%, IMRrural: +10.6%; 7.6% to 13.6%). By contrast, among infants of non-Greek mothers, the low starting IMR/ENMR/LNMR/PNMR increased significantly (max ENMR:+12.5%; 8.6% to 16.5%) leading to a non-significant time–trend pattern overall in Greece. The inverse associations of HDI with IMR, ENMR and PNMR were restricted to Greek mothers’ infants. Joinpoint regression analyses among Greek mothers’ infants indicated non-significant increasing trends of IMR and ENMR following the crisis (+9.3%, 2012–2016, p=0.07 and +10.2%, 2011–2016, p=0.06, respectively). By contrast, the high (+17.1%; 8.1% to 26.9%, p=0.002) IMR increases among non-Greek infants were restricted to 2004–2011 and equalised to those of Greek mothers’ infants thereafter. ITS analyses in preset years (2008, 2010, 2012) identified significantly increasing trends in IMR, LNMR and PNMR after 2012, and in ENMR after 2010, among Greek mothers’ infants.ConclusionsHDI and rural residence were significantly associated with IMR. The strongly decreasing IMR trends among Greek-mothers’ infants were stagnated after a lag time of ~4 years of crisis approximating the previously sharply increasing trends among non-Greeks.

BACKGROUND The systematic evaluation of the results of time-series studies of air pollution is challenged by differences in model specification and publication bias. METHODS We evaluated the associations of inhalable particulate matter (PM) with an aerodynamic diameter of 10 μm or less (PM10) and fine PM with an aerodynamic diameter of 2.5 μm or less (PM2.5) with daily all-cause, cardiovascular, and respiratory mortality across multiple countries or regions. Daily data on mortality and air pollution were collected from 652 cities in 24 countries or regions. We used overdispersed generalized additive models with random-effects meta-analysis to investigate the associations. Two-pollutant models were fitted to test the robustness of the associations. Concentration–response curves from each city were pooled to allow global estimates to be derived. RESULTS On average, an increase of 10 μg per cubic meter in the 2-day moving average of PM10 concentration, which represents the average over the current and previous day, was associated with increases of 0.44% (95% confidence interval [CI], 0.39 to 0.50) in daily all-cause mortality, 0.36% (95% CI, 0.30 to 0.43) in daily cardiovascular mortality, and 0.47% (95% CI, 0.35 to 0.58) in daily respiratory mortality. The corresponding increases in daily mortality for the same change in PM2.5 concentration were 0.68% (95% CI, 0.59 to 0.77), 0.55% (95% CI, 0.45 to 0.66), and 0.74% (95% CI, 0.53 to 0.95). These associations remained significant after adjustment for gaseous pollutants. Associations were stronger in locations with lower annual mean PM concentrations and higher annual mean temperatures. The pooled concentration–response curves showed a consistent increase in daily mortality with increasing PM concentration, with steeper slopes at lower PM concentrations. CONCLUSIONS Our data show independent associations between short-term exposure to PM10 and PM2.5 and daily all-cause, cardiovascular, and respiratory mortality in more than 600 cities across the globe. These data reinforce the evidence of a link between mortality and PM concentration established in regional and local studies. (Funded by the National Natural Science Foundation of China and others.) Copyright © 2019 Massachusetts Medical Society., Funding text #1 Our data show independent associations between short-term exposure to PM10 and PM2.5 and daily all-cause, cardiovascular, and respiratory mortality in more than 600 cities across the globe. These data reinforce the evidence of a link between mortality and PM concentration established in regional and local studies. (Funded by the National Natural Science Foundation of China and others.) Funding text #2 Supported by the National Natural Science Foundation of China (grants 91843302 and 91643205, to Dr. Kan); the China Medical Board Collaborating Program (grant 16-250); the Medical Research Council, United Kingdom (grants MR/R013349/1 and MR/M022625/1, to Drs. Gasparrini, Sera, and Vicedo-Cabrera); the Career Development Fellowship of the Australian National Health and Medical Research Council (grants APP1107107 and APP1163693, to Dr. Guo); the Ministry of Education of Spain (grant PRX17/00705, to Dr. Tobias); the National Plan for I+D+I (grant PI15/00515), cofunded by the Instituto de Salud Carlos III Directorate General for Evaluation and the European Regional Development Fund (FEDER); the Global Research Laboratory (grant K21004000001-10A0500-00710 from the National Research Foundation of Korea, funded by the Ministry of Science, Information and Communication Technologies, to Dr. Kim); the Academy of Finland (grants 310372 and 310373, to Drs. Jaakkola and Ryti); the Estonian Ministry of Education and Research (grant IUT34-17, to Drs. Orru and Indermitte); the Czech Science Foundation (grant 18-22125S, to Drs. Kyselý and Urban); and a Professional Services Agreement with the Health Effects Institute, United States (to Dr. Cohen).View less Funding text #3 The authors’ affiliations are as follows: the School of Public Health, Key Laboratory of Public Health Safety of the Ministry of Education and National Health Commission Key Laboratory of Health Technology Assessment (C.L., R.C., H. Kan), the Department of Environmental Science and Engineering (J. Chen), Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (R.C., H. Kan), Fudan University, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine (S.T.), and Children’s Hospital of Fudan University, National Center for Children’s Health (H. Kan), Shanghai, the School of Public Health and Management, Binzhou Medical University, Yantai (Y.G.), the School of Public Health, Institute of Environment and Population Health, Anhui Medical University, Hefei (S.T.), and the Key Laboratory of Environment and Health, Ministry of Education, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (T.W.) — all in China; the Department of Public Health, Environments and Society (F.S., A.M.V.-C., A.M., A.G.) and the Centre for Statistical Methodology (A.G.), London School of Hygiene and Tropical Medicine, and the School of Population Health and Environmental Sciences, King’s College London (K.K.), London; the Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC (Y.G.), and the School of Public Health and Social Work, Queensland University of Technology, Brisbane (S.T.) — both in Australia; the Institute of Advanced Studies, University of São Paulo, São Paulo (M.S.Z.S.C., P.H.N.S.); the Air Health Science Division, Health Canada, and the School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON (E.L.); the Department of Public Health (P.M.) and the School of Nursing and Obstetrics (N.V.O.), Universidad de los Andes, Santiago, Chile; Hospital Vista Hermosa, Bogota, Colombia (S.O.G.); Santé Publique France, French National Public Health Agency, Saint Maurice, France (M.P.); the Department of Epidemiology, Lazio Regional Health Service–ASL Roma 1, Rome (M. Stafoggia, M. Scortichini); Karolinska Institute, Institute of Environmental Medicine, Stockholm (M. Stafoggia), and the Department of Public Health and Clinical Medicine, Umeå University, Umeå (B.F., C.Å., H.O.) — both in Sweden; the Department of Pediatric Infectious Diseases, Institute of Tropical Medicine, Nagasaki University, Nagasaki (M.H.), and the Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba (Y.H.) — both in Japan; the Department of Environmental Health, National Institute of Pub

Background It is known that on days with high temperatures higher mortality is observed and there is a minimum mortality temperature (MMT) point which is higher in places with warmer climate. This indicates some population adaptation to local climate but information on how quickly this adaptation will occur under climate change is lacking. Methods To investigate this, we associated daily mortality data with temperature during the warm period in 2004–2013 for London inhabitants born in five climatic zones (UK, Tropical, Sub-tropical, Boreal and Mixed). We fitted Poisson regression with distributed-lag non-linear models for each climatic zone group separately to estimate group-specific exposure-response associations and MMTs. We report relative risks of death comparing the 95th percentile (21 °C) and maximum (25 °C) of the temperature distribution in London with the zone-specific minimum mortality temperature. Results No heat-related mortality was observed for people born in countries with Sub-tropical and Mixed climates. We observed an increase of 26%, 35% and 39% in the risk of death at 25 °C compared to the MMT in people born in the UK (marine climate), Tropical and Boreal climate respectively. The temperatures with the lowest mortality in these groups ranged from 15.9 to 17.7 °C. Discussion Our findings imply that people born in different climatic zones do not adapt fully to their new environment within their lifetime. This implies that populations may not adapt readily to climate change and will suffer increased effects from heat. In the presence of climate change, policy makers should be aware of a delayed process of adaptation.

Background Critical care management of patients undergoing transcatheter aortic valve implantation (TAVI) is a major determinant of their outcome. Aims The aim of this study was to compare the prognostic performance of four general scoring systems [Acute Physiology and Chronic Health Evaluation (APACHE), Simplified Acute Physiology Score (SAPS), Sequential Organ Failure Assessment (SOFA), and MultiOrgan Dysfunction (MOD) scores] in TAVI patients. Methods Between 1 June 2008 and 30 June 2014, 75 patients (81.2 ± 6.4 years old, 36 men and 39 women) who underwent TAVI were scored during the first 24 h of their stay at the intensive care unit (ICU). The outcome measures were in-hospital and 30-day mortality and in-hospital and 30-day morbidity defined as myocardial infarction, implantation of permanent pacemaker, stroke, tamponade, major bleeding, vascular access site complications and prolonged ventilation. Results Four patients (5.3%) died in ICU and one more during follow-up, indicating a 30-day mortality rate of 6.6%. Regarding in-hospital mortality, the area under the ROC curve (AUC) was 0.92 for SAPS II, 0.88 for APACHE II, 0.73 for MODS and 0.74 for SOFA. Regarding 30 day-mortality, SAPS II and APACHE II performed equally higher (AUC = 0.88) than the other two scores (0.79 for MODS and 0.80 for SOFA). SAPS II had the best calibration among all four scores for in-hospital and 30-day mortality ( χ2 = 3.06 and χ2 = 3.29, respectively). AUCs for in-hospital and 30-day morbidity were above 0.7 for SAPS II and APACHE II. Conclusions SAPS II and APACHE II are reliable mortality and morbidity risk stratification models for TAVI patients with high calibration and discrimination.

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

We studied the potential synergy between air pollution and meteorology and their impact on mortality in nine European cities with data from 2004 to 2010. We used daily series of Apparent Temperature (AT), measurements of particulate matter (PM10), ozone (O3), and nitrogen dioxide (NO2) and total non-accidental, cardiovascular, and respiratory deaths. We applied Poisson regression for city-specific analysis and random effects meta-analysis to combine city-specific results, separately for the warm and cold seasons. In the warm season, the percentage increase in all deaths from natural causes per &deg, C increase in AT tended to be greater during high ozone days, although this was only significant for all ages when all causes were considered. On low ozone days, the increase in the total daily number of deaths was 1.84% (95% CI 0.87, 2.82), whilst it was 2.20% (95% CI 1.28, 3.13) in the high ozone days per 1 &deg, C increase in AT. Interaction with PM10 was significant for cardiovascular (CVD) causes of death for all ages (2.24% on low PM10 days (95% CI 1.01, 3.47) whilst it is 2.63% (95% CI 1.57, 3.71) on high PM10 days) and for ages 75+. In days with heat waves, no consistent pattern of interaction was observed. For the cold period, no evidence for synergy was found. In conclusion, some evidence of interactive effects between hot temperature and the levels of ozone and PM10 was found, but no consistent synergy could be identified during the cold season.

BACKGROUND: Inflammation plays an important role in the initiation and progression of acute aortic dissection (AAD). New inflammatory indices derived from full cell blood count and its differential may be associated with increased risk. We evaluated platelet‐lymphocyte (PLR), red cell distribution width (RDW) and RDW/PLT's (platelets) (RPR) in AAD. METHODS: We studied 120 consecutive patients with AAD type I admitted for emergency surgery (group I), 121 consecutive patients with aortic aneurysms of the ascending aorta prior to elective repair (group II) and 121 controls (group III), age and sex matched. RESULTS: PLR was significantly higher in group I vs both groups II and III (P

Purpose To evaluate the efficacy of synbiotic formula with partial whey hydrolysate and high magnesium content in infants presenting with functional constipation. Methods Sixty-five infants with functional constipation were included. Forty infants were treated during one month with parental reassurance and the intervention formula and were compared to a control group of 25 infants treated with parental reassurance only. Parents completed a quality of life (QoL) questionnaire at baseline and during the last week of the study. Results At inclusion, stool characteristics and QoL were similar in both groups. The control group was slightly older than the intervention group (7.5±3.9 vs. 6.2±3.6 weeks). At onset, stool composition was "hard and tight" (Bristol stool scale 1 and 2) in all infants. After one month, stool composition remained unchanged in the control group except in two infants that developed "creamy" stools (Bristol stool scale type 3 and 4). In the intervention group, stools remained "hard and tight" in 27.5%, and became "creamy" in 47.5%, "loose" (Bristol stool scale type 5) in 22.5% and "watery" (Bristol stool type 6 and 7) in 2.5%. The benefit of the intervention formula was estimated to be "very important" in 70%. The median scores for QoL improved significantly in the intervention group for all parameters and for one in the control group. Conclusion The intervention formula significantly improved functional constipation resulting in a better QoL of the parents and infants.

Legislation controlling vehicle emissions has been credited with a general downward trend in NOx (NO2+NO) concentrations in Europe since the 1990's. However, recent studies suggest that traffic (roadside) (TR) NO2 concentrations have not decreased as expected, and in some cases increased, most likely due to the use of oxidation catalysts and particle filters in diesel vehicles (EURO III, IV, V, VI). In this study we describe the time trends in NOx, NO2 and NO concentrations in 9 European cities comparing TR and urban background (UB) monitoring locations. In each city, we collected hourly city-specific NOx, NO, and NO2 data from one TR and one UB monitoring site for each year. We describe hourly, weekly, seasonal and inter-annual patterns for periods corresponding to the implementation dates of various EURO vehicle emission standards regulating NOx emissions. The diurnal patterns in all 9 cities strongly reflected morning and evening traffic. In addition, lower weekend concentrations were observed. The NOx concentrations from the TR sites remain unchanged in the majority of the cities over the study period. When stratified by 3 time periods according to the implementation of the EURO standards, an increasing NO2/NOx ratio in 7/9 cities with time was noted. However, over the same time period the NO/NO2 ratio decreased in 8/9 cities. A permanent inversion of the NO/NO2 ratio was observed to occur in 2003 in 5/9 cities. Our analyses of temporal and diurnal patterns of NOx in European cities show reductions in concentrations consistent with reductions in primary emissions likely arising from the implementation of successive EURO standards. The generally constant or increasing NO2 concentrations in the majority of the cities assessed over the study period underline the need of further regulative measures to meet the air quality standards and consequently to minimise adverse effects on human health. The ongoing collection and analysis of pollution concentrations across the EU is recommended to monitor trends in pollutants associated with adverse health effects.

Epidemiological time series studies suggest daily temperature and humidity are associated with adverse health effects including increased mortality and hospital admissions. However, there is no consensus over which metric or lag best describes the relationships. We investigated which temperature and humidity model specification most adequately predicted mortality in three large European cities. Daily counts of all-cause mortality, minimum, maximum and mean temperature and relative humidity and apparent temperature (a composite measure of ambient and dew point temperature) were assembled for Athens, London, and Rome for 6 years between 1999 and 2005. City-specific Poisson regression models were fitted separately for warm (April-September) and cold (October-March) periods adjusting for seasonality, air pollution, and public holidays. We investigated goodness of model fit for each metric for delayed effects up to 13 days using three model fit criteria: sum of the partial autocorrelation function, AIC, and GCV. No uniformly best index for all cities and seasonal periods was observed. The effects of temperature were uniformly shown to be more prolonged during cold periods and the majority of models suggested separate temperature and humidity variables performed better than apparent temperature in predicting mortality. Our study suggests that the nature of the effects of temperature and humidity on mortality vary between cities for unknown reasons which require further investigation but may relate to city-specific population, socioeconomic, and environmental characteristics. This may have consequences on epidemiological studies and local temperature-related warning systems.

Background: Previous studies examined the effect of laparoscopic cholecystectomy (LC) versus open cholecystectomy (OC) on physiological variables of the respiratory system. In this study we compared changes in arterial blood gases-related parameters between LC and OC to assess their comparative influence on gas exchange. Methods: We studied 28 patients, operated under identical anesthetic protocol (LC: 18 patients, OC: 10 patients). Measurements were made on the morning before surgery (BS), the second (AS2) and the eighth (AS8) postoperative day. Studied parameters, including alveolar-arterial difference in PO 2 ((A-a)DO 2 ) and oxygen content (Oct in vol%), were statistically compared. Results: On AS2 a greater increase was found in ((A-a)DO 2 ) for the OC compared to LC (4.673 ± 0.966 kPa versus 3.773 ± 1.357 kPa, respectively). Between BS and AS2, Oct in vol% decreased from 17.55 ± 1.90 to 15.69 ± 1.88 in the LC and from 16.99 ± 2.37 to 14.62 ± 2.23 in the OC, whilst a reduction (P = 0.093) between AS2 and AS8 was also found for the open method. Besides, on AS2, SaO 2 % decrease was greater in OC compared to LC (P = 0.096). Conclusions: On AS2, the greater increase in OC-((A-a)DO 2 ) associated with Oct in vol% and SaO 2 % findings also in OC group suggest that LC might be associated with lower risk for impaired tissue oxygenation. J Clin Med Res. 2015;7(4):232-241 doi: http://dx.doi.org/10.14740/jocmr2086w

OBJECTIVES Given that cytology of adenocarcinoma-induced pleural effusions has a high diagnostic yield, we have comparatively evaluated the cytological information of smears during biphasic sampling of pleural fluid in patients with metastatic pleural adenocarcinoma from various primary sites. METHODS We studied 25 male and 21 female patients, aged 59.4 ±17.2 years (mean ± SD) with unilateral malignant effusion of varying magnitude due to confirmed adenocarcinoma from various primary sites. At thoracocentesis we collected two 30-ml samples of pleural fluid, the first at the very beginning of fluid aspiration (S1) and the second just before termination of fluid removal (S2) and recorded the volume of fluid aspirated between the 2 samples. Cytological smears were examined under light microscopy by 3 independent cytologists after Papanicolaou stain. Quantitative assessment of cell types was averaged among 50 visual fields for each smear. RESULTS In S1 versus S2 the mean number of mesothelial cells was 7.8 ± 4.8 versus 12.1 ± 5.4 (mean ± SD), of lymphocytes 64.6 ± 12.9 versus 85.9 ± 17.4, of neutrophils 8.5 ± 4.4 versus 11.7 ± 5.2, of eosinophils 1.5 ± 0.3 versus 1.7 ± 0.8, and the number of malignant cell aggregates(NMCA) was 11.9 ±4.9 versus 20.7 ± 5.1. The differences in numbers of all cell types including NMCA were statistically significant between S1 and S2 (P