Associations Between Extreme Temperatures and Cardiovascular Cause-Specific Mortality: Results From 27 Countries.

BACKGROUND Cardiovascular disease is the leading cause of death worldwide. Existing studies on the association between temperatures and cardiovascular deaths have been limited in geographic zones and have generally considered associations with total cardiovascular deaths rather than cause-specific cardiovascular deaths. METHODS We used unified data collection protocols within the Multi-Country Multi-City Collaborative Network to assemble a database of daily counts of specific cardiovascular causes of death from 567 cities in 27 countries across 5 continents in overlapping periods ranging from 1979 to 2019. City-specific daily ambient temperatures were obtained from weather stations and climate reanalysis models. To investigate cardiovascular mortality associations with extreme hot and cold temperatures, we fit case-crossover models in each city and then used a mixed-effects meta-analytic framework to pool individual city estimates. Extreme temperature percentiles were compared with the minimum mortality temperature in each location. Excess deaths were calculated for a range of extreme temperature days. RESULTS The analyses included deaths from any cardiovascular cause (32 154 935), ischemic heart disease (11 745 880), stroke (9 351 312), heart failure (3 673 723), and arrhythmia (670 859). At extreme temperature percentiles, heat (99th percentile) and cold (1st percentile) were associated with higher risk of dying from any cardiovascular cause, ischemic heart disease, stroke, and heart failure as compared to the minimum mortality temperature, which is the temperature associated with least mortality. Across a range of extreme temperatures, hot days (above 97.5th percentile) and cold days (below 2.5th percentile) accounted for 2.2 (95% empirical CI [eCI], 2.1-2.3) and 9.1 (95% eCI, 8.9-9.2) excess deaths for every 1000 cardiovascular deaths, respectively. Heart failure was associated with the highest excess deaths proportion from extreme hot and cold days with 2.6 (95% eCI, 2.4-2.8) and 12.8 (95% eCI, 12.2-13.1) for every 1000 heart failure deaths, respectively. CONCLUSIONS Across a large, multinational sample, exposure to extreme hot and cold temperatures was associated with a greater risk of mortality from multiple common cardiovascular conditions. The intersections between extreme temperatures and cardiovascular health need to be thoroughly characterized in the present day-and especially under a changing climate

Associations Between Extreme Temperatures and Cardiovascular Cause-Specific Mortality: Results From 27 Countries

Background: Cardiovascular disease is the leading cause of death worldwide. Existing studies on the association between temperatures and cardiovascular deaths have been limited in geographic zones and have generally considered associations with total cardiovascular deaths rather than cause-specific cardiovascular deaths. Methods: We used unified data collection protocols within the Multi-Country Multi-City Collaborative Network to assemble a database of daily counts of specific cardiovascular causes of death from 567 cities in 27 countries across 5 continents in overlapping periods ranging from 1979 to 2019. City-specific daily ambient temperatures were obtained from weather stations and climate reanalysis models. To investigate cardiovascular mortality associations with extreme hot and cold temperatures, we fit case-crossover models in each city and then used a mixed-effects meta-analytic framework to pool individual city estimates. Extreme temperature percentiles were compared with the minimum mortality temperature in each location. Excess deaths were calculated for a range of extreme temperature days. Results: The analyses included deaths from any cardiovascular cause (32 154 935), ischemic heart disease (11 745 880), stroke (9 351 312), heart failure (3 673 723), and arrhythmia (670 859). At extreme temperature percentiles, heat (99th percentile) and cold (1st percentile) were associated with higher risk of dying from any cardiovascular cause, ischemic heart disease, stroke, and heart failure as compared to the minimum mortality temperature, which is the temperature associated with least mortality. Across a range of extreme temperatures, hot days (above 97.5th percentile) and cold days (below 2.5th percentile) accounted for 2.2 (95% empirical CI [eCI], 2.1–2.3) and 9.1 (95% eCI, 8.9–9.2) excess deaths for every 1000 cardiovascular deaths, respectively. Heart failure was associated with the highest excess deaths proportion from extreme hot and cold days with 2.6 (95% eCI, 2.4–2.8) and 12.8 (95% eCI, 12.2–13.1) for every 1000 heart failure deaths, respectively. Conclusions: Across a large, multinational sample, exposure to extreme hot and cold temperatures was associated with a greater risk of mortality from multiple common cardiovascular conditions. The intersections between extreme temperatures and cardiovascular health need to be thoroughly characterized in the present day—and especially under a changing climate.Clinical Perspective_ What Is New?: This study provided evidence from what we believe is the largest multinational dataset ever assembled on cardiovascular outcomes and environmental exposures; Extreme hot and cold temperatures were associated with increased risk of death from any cardiovascular cause, ischemic heart disease, stroke, and heart failure; For every 1000 cardiovascular deaths, 2 and 9 excess deaths were attributed to extreme hot and cold days, respectively. _ What Are the Clinical Implications?: Extreme temperatures from a warming planet may become emerging priorities for public health and preventative cardiology; The findings of this study should prompt professional cardiology societies to commission scientific statements on the intersections of extreme temperature exposure and cardiovascular health.This study was supported by the Kuwait Foundation for the Advancement of Science (CB21-63BO-01); the US Environmental Protection Agency (RD-835872); Harvard Chan National Institute of Environmental Health Sciences Center for Environmental Health (P01ES009825); the UK Medical Research Council (MR/R013349/1); the UK Natural Environment Research Council (NE/R009384/1); the European Union’s Horizon 2020 Project Exhaustion (820655); the Australian National Health and Medical Research Council (APP 2000581, APP 1109193, APP 1163693); the National Institute of Environmental Health Sciences–funded HERCULES Center (P30ES019776); the MCIN/AEI/10.13039/501100011033 (grant CEX2018-000794-S); the Taiwanese Ministry of Science and Technology (MOST 109–2621-M-002–021); the Environmental Restoration and Conservation Agency, Environment Research and Technology Development Fund (JPMEERF15S11412); the São Paulo Research Foundation; and Fundação para a Ciência e a Tecnlogia (SFRH/BPD/115112/2016)info:eu-repo/semantics/publishedVersio

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

The long-term impact of restricting cycling and walking during high air pollution days on all-cause mortality: Health impact Assessment study.

Regular active commuting, such as cycling and walking to and from the workplace, is associated with lower all-cause mortality through increased physical activity (PA). However, active commuting may increase intake of fine particles (PM2.5), causing negative health effects. The purpose of this study is to estimate the combined risk of PA and air pollution for all-cause mortality among active commuters who, on days with high PM2.5 levels, switch to commuting by public transportation or work from home. Towards this purpose, we developed a Health Impact Assessment model for six cities (Helsinki, London, Sao Paulo, Warsaw, Beijing, New Delhi) using daily, city-specific PM2.5 concentrations. For each city we estimated combined Relative Risk (RR) due to all-cause mortality for the PA benefits and PM2.5 risks with different thresholds concentrations. Everyday cycling to work resulted in annual all-cause mortality risk reductions ranging from 28 averted deaths per 1000 cyclists (95% confidence interval (CI): 20-38) in Sao Paolo to 12 averted deaths per 1000 cyclists (95% CI: 5-19) in Beijing. Similarly, for everyday walking, the reductions in annual all-cause mortality ranged from 23 averted deaths per 1000 pedestrians (95 CI: 16-31) in Sao Paolo to 10 averted deaths per 1000 pedestrians (95%CI: 5-16) in Beijing. Restricting active commuting during days with PM2.5 levels above specific air quality thresholds would not decrease all-cause mortality risk in any examined city. On the contrary, all-cause mortality risk would increase if walking and cycling are restricted in days with PM2.5 concentrations below 150 μg/m3 in highly polluted cities (Beijing, New Delhi). In all six cities, everyday active commuting reduced all-cause mortality when benefits of PA and risk or air pollution were combined. Switching to working from home or using public transport on days with high air pollution is not expected to lead to improved all-cause mortality risks.MT and JW: The work was undertaken by the Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research Centre of Excellence. This study was supported by the project “Towards an Integrated Global Transport and Health Assessment Tool (TIGTHAT)”, funded by Medical Research Council (MRC) Global Challenges Research Fund, UK (number: RG87632-SJ). Funding from the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, the National Institute for Health Research, and the Wellcome Trust, under the auspices of the UK Clinical Research Collaboration, is gratefully acknowledged. GY and PK were supported by Cyprus University of Technology Starting Grant (Stefania Papatheodorou). The sponsors had no role or involvement in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication

Statins to mitigate cardiotoxicity in cancer patients treated with anthracyclines and/or trastuzumab: a systematic review and meta-analysis

PurposeCardiotoxicity affects 5-16% of cancer patients who receive anthracyclines and/or trastuzumab. Limited research has examined interventions to mitigate cardiotoxicity. We examined the role of statins in mitigating cardiotoxicity by performing a systematic review and meta-analysis of published studies.MethodsA literature search was conducted using PubMed, Embase, Web of Science, ClinicalTrials.gov, and Cochrane Central. A random-effect model was used to assess summary relative risks (RR), weighted mean differences (WMD), and corresponding 95% confidence intervals. Testing for heterogeneity between the studies was performed using Cochran's Q test and the I2 test.ResultsTwo randomized controlled trials (RCTs) with a total of 117 patients and four observational cohort studies with a total of 813 patients contributed to the analysis. Pooled results indicate significant mitigation of cardiotoxicity after anthracycline and/or trastuzumab exposure among statin users in cohort studies [RR = 0.46, 95% CI (0.27-0.78), p = 0.004, [Formula: see text] = 0.0%] and a non-significant decrease in cardiotoxicity risk among statin users in RCTs [RR = 0.49, 95% CI (0.17-1.45), p = 0.20, [Formula: see text] = 5.6%]. Those who used statins were also significantly more likely to maintain left ventricular ejection fraction compared to baseline after anthracycline and/or trastuzumab therapy in both cohort studies [weighted mean difference (WMD) = 6.14%, 95% CI (2.75-9.52), p &lt; 0.001, [Formula: see text] = 74.7%] and RCTs [WMD = 6.25%, 95% CI (0.82-11.68, p = 0.024, [Formula: see text] = 80.9%]. We were unable to explore publication bias due to the small number of studies.ConclusionThis meta-analysis suggests that there is an association between statin use and decreased risk of cardiotoxicity after anthracycline and/or trastuzumab exposure. Larger well-conducted RCTs are needed to determine whether statins decrease risk of cardiotoxicity from anthracyclines and/or trastuzumab.Trial registration number and date of registrationPROSPERO: CRD42020140352 on 7/6/2020

Clarithromycin use and the risk of mortality and cardiovascular events: A systematic review and meta-analysis.

BACKGROUND:Although studies reported increased cardiovascular (CV) risks in patients treated with macrolides, the risks remain controversial among clarithromycin (CLR) users. We aimed to summarize the association between CLR use and the risks of mortality and CV events. METHODS:We searched PubMed, EMBASE, Web of Science, and the Cochrane Library for randomized controlled trials (RCTs) and observational studies with population exposed to CLR published until December 31st, 2018. These studies reported either all-cause mortality (primary outcome) or CV adverse events (secondary outcomes) based on multivariate models. Effect measures were synthesized by study design and follow-up duration (long-term, ≥ 1 year; short-term, ≤ 3 months; and immediate, ≤ 2 weeks). This study has been registered on PROSPERO (ID: CRD42018089605). RESULTS:This meta-analysis included 13 studies (3 RCTs and 10 observational studies) and 8,351,815 subjects (1,124,672 cases and 7,227,143 controls). Overall, CLR use was not associated with increased long-term all-cause mortality (pooled rate ratio RR = 1.09, 95% CI = 0.91-1.32), either among patients with or without comorbidities of cardiovascular diseases. Comparing CLR users to placebo, there is no additional risks of cardiac mortality (pooled RR = 1.03, 95% CI = 0.53-2.01), acute myocardial infarction (pooled RR = 1.29, 95% CI = 0.98-1.68), and arrhythmia (pooled RR = 0.90, 95% CI = 0.62-1.32). CONCLUSIONS:Our findings suggested no significant association between CLR use and subsequent long-term all-cause mortality, regardless having comorbidity of cardiovascular diseases or not. Further RCTs investigating the short-term CV risks of CLR use compared to alternative antibiotics are warranted, particularly in high-risk populations

Temperature and hospital admissions in the Eastern Mediterranean: a case study in Cyprus

Exposure to extreme temperatures can trigger a cascade of adverse cardiovascular and respiratory events. However, in Cyprus, a hotspot of climate change in the Eastern Mediterranean region, little is known about the temperature-related cardiorespiratory morbidity risks. We analyzed daily counts of hospital admissions for cardiovascular and respiratory diseases from four general hospitals in three districts in Cyprus from 2000 through 2019. For each district, we fitted time-series quasi-Poisson regression with distributed lag non-linear models to analyze the associations between daily mean temperature (lag 0–21 d) and hospital admissions for cardiorespiratory, cardiovascular, and respiratory diseases. A random-effects meta-analytical model was then applied to pool the district-specific estimates and obtain the national average associations. We analyzed 20 years of cause-specific hospitalization data with a total of 179 988 cardiovascular and respiratory events. The relationships between cardiorespiratory morbidity and temperature were overall U-shaped. During extreme temperature days, 15.85% (95% empirical CI [eCI]: 8.24, 22.40%) excess cardiovascular hospitalizations and 9.59% (95% eCI: −0.66, 18.69%) excess respiratory hospitalizations were attributable to extreme cold days (below the 2.5th percentile). Extreme hot days (above the 97.5th percentile) accounted for 0.17% (95% eCI: 0.03, 0.29%) excess cardiovascular hospitalizations and 0.23% (95% eCI: 0.07, 0.35%) excess respiratory hospitalizations. We found evidence of increased cardiovascular morbidity risk associated with extreme temperatures in Cyprus. Our study highlights the necessity to implement public health interventions and adaptive measures to mitigate the related temperature effects in an understudied region

MEDEA randomised intervention study protocol in Cyprus, Greece and Israel for mitigation of desert dust health effects in adults with atrial fibrillation

Introduction Mediterranean countries experience frequent desert dust storm (DDS) events originating from neighbouring Sahara and Arabian deserts, which are associated with significant increase in mortality and hospital admissions, mostly from cardiovascular and respiratory diseases. Short-term exposure to ambient air pollution is considered as a trigger for symptomatic exacerbations of pre-existing paroxysmal atrial fibrillation (AF) and other types of heart arrhythmia. The Mitigating the Health Effects of Desert Dust Storms Using Exposure-Reduction Approaches clinical randomised intervention study in adults with AF is funded by EU LIFE+programme to evaluate the efficacy of recommendations aiming to reduce exposure to desert dust and related heart arrhythmia effects.Methods and analysis The study is performed in three heavily exposed to desert dust regions of the Eastern Mediterranean: Cyprus, Israel and Crete-Greece. Adults with paroxysmal AF and implanted pacemaker are recruited and randomised to three parallel groups: (a) no intervention, (b) interventions to reduce outdoor exposure to desert dust, (c) interventions to reduce both outdoor and indoor exposure to particulate matter during desert dust episodes. Eligible participants are enrolled on a web-based platform which communicates, alerts and makes exposure reduction recommendations during DDS events. Exposure changes are assessed by novel tools (smartwatches with Global Positioning System and physical activity sensors, air pollution samplers assessing air quality inside and outside participant’s homes, etc). Clinical outcomes include the AF burden expressed as the percentage of time with paroxysmal AF over the total study period, the incidence of ventricular arrhythmia episodes as recorded by the participants’ pacemakers or cardioverters/defibrillators and the disease-specific Atrial Fibrillation Effect on QualiTy-of-Life questionnaire.Ethics and dissemination Local bioethics’ authorities approved the study at all sites, according to national legislations (Cyprus: National Bioethics Committee, Data Protection Commissioner and Ministry of Health; Greece, Scientific Committee and Governing Board of the University General Hospital of Heraklion; Israel: Institutional Review Board (‘Helsinki committee’) of the Soroka University Medical Center). The findings will be publicised in peer-reviewed scientific journals, in international conferences and in professional websites and newsletters. A summary of the results and participants’ interviews will be included in a documentary in English, Greek and Hebrew.Trial registration number ClinicalTrials.gov Identifier; NCT03503812

The effect of l -Arginine on Ciliary Beat Frequency in PCD patients, non-PCD respiratory patients and healthy controls

Objectives Few studies have examined the potentially therapeutic effect of increasing the production of endogenous nitric oxide (NO) in Primary Ciliary Dyskinesia (PCD) and other chronic respiratory conditions. Nasal NO is low in PCD and has been found to correlate with compromised Ciliary Beat Frequency (CBF). In this study we assessed the effect of increasing L-Arginine, as the substrate of NO synthases, on CBF in biopsies of human respiratory ciliated epithelium. Methodology A total of 28 suspect cases with chronic respiratory manifestations referred for PCD diagnostic testing and 8 healthy controls underwent nasal brushing. Obtained epithelial cells were divided between three culture medium 199 solutions, containing different levels of L-Arginine (0.33 mM as baseline, 1 mM and 10 Mm as increased levels). CBF measurements were obtained at 37 °C and 25 °C at 1, 3 and 24 h after sample acquisition. Results Among a total of 36 recruited subjects, 8 had PCD confirmed (PCD n = 8), 20 had PCD excluded (non-PCD n = 20) and 8 were healthy controls (Healthy Controls = 8). Among PCD subjects, ciliary motility was characterized by rotational (n = 5) or dyskinetic (n = 3) beating. At 37 °C, compared to baseline, higher levels of L-Arginine resulted in up to 9% CBF increase at 1 h (p = 0.007), up to 9% CBF increase at 3 h (p < 0.001) and up to 12% CBF increase at 24 h (p = 0.002). Similar although smaller scale increases were recorded at 25 °C. The effect of L-Arginine was time dependent (interaction p = 0.002) and was similar in PCD patients, non-PCD chronic respiratory patients and healthy controls (interaction p = 0.800). Conclusions L-Arginine increases CBF and merits to be evaluated as a potential stimulator of mucociliary clearance in chronic respiratory conditions and congenital ciliary disorders with residual motility. Larger human studies are needed to confirm these findings