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Background: Atrial fibrillation (AF) is a common arrhythmia classified as paroxysmal and non-paroxysmal. Non-paroxysmal AF is associated with an increased risk of complications. Diabetes contributes to AF initiation, yet its role in AF maintenance is unclear. We conducted a systematic review and meta-analysis to summarize the evidence regarding the association of diabetes with AF types., Methods: We searched 5 databases for observational studies investigating the association of diabetes with the likelihood of an AF type (vs another type) in humans. Study quality was evaluated using the Newcastle-Ottawa Scale. Studies classifying AF types as paroxysmal (reference) and non-paroxysmal were pooled in a meta-analysis using random effects models., Results: Of 1997 articles we identified, 20 were included in our systematic review. The population sample size ranged from 64 to 9816 participants with mean age ranging from 40 to 75 years and percentage of women from 24.8 to 100%. The quality of studies varied from poor (60%) to fair (5%) to good (35%). In the systematic review, 8 studies among patients with AF investigated the cross-sectional association of diabetes with non-paroxysmal AF (vs paroxysmal) of which 6 showed a positive association and 2 showed no association. Fourteen studies investigated the longitudinal association of diabetes with "more sustained" AF types (vs "less sustained") of which 2 showed a positive association and 12 showed no association. In the meta-analysis of cross-sectional studies, patients with AF and diabetes were 1.31-times more likely to have non-paroxysmal AF than those without diabetes [8 studies; pooled OR (95% CI), 1.31 (1.13-1.51), I 2  = 82.6%]. The meta-analysis of longitudinal studies showed that for patients with paroxysmal AF, diabetes is associated with 1.32-times increased likelihood of progression to non-paroxysmal AF [five studies; pooled OR (95% CI), 1.32 (1.07-1.62); I 2  = 0%]., Conclusions: Our findings suggest that diabetes is associated with an increased likelihood of non-paroxysmal AF rather than paroxysmal AF. However, further high quality studies are needed to replicate these findings, adjust for potential confounders, elucidate mechanisms linking diabetes to non-paroxysmal AF, and assess the impact of antidiabetic medications on AF types. These strategies could eventually help decrease the risk of non-paroxysmal AF among patients with diabetes., (© 2021. The Author(s).)

Background Diabetes is a major risk factor for atrial fibrillation (AF). However, it remains unclear whether individual AF phenotype and related comorbidities differ between patients who have AF with and without diabetes. This study investigated the association of diabetes with AF phenotype and cardiac and neurological comorbidities in patients with documented AF. Methods and Results Participants in the multicenter Swiss-AF (Swiss Atrial Fibrillation) study with data on diabetes and AF phenotype were eligible. Primary outcomes were parameters of AF phenotype, including AF type, AF symptoms, and quality of life (assessed by the European Quality of Life-5 Dimensions Questionnaire [EQ-5D]). Secondary outcomes were cardiac (ie, history of hypertension, myocardial infarction, and heart failure) and neurological (ie, history of stroke and cognitive impairment) comorbidities. The cross-sectional association of diabetes with these outcomes was assessed using logistic and linear regression, adjusted for age, sex, and cardiovascular risk factors. We included 2411 patients with AF (27.4% women; median age, 73.6 years). Diabetes was not associated with nonparoxysmal AF (odds ratio [OR], 1.01; 95% CI, 0.81-1.27). Patients with diabetes less often perceived AF symptoms (OR, 0.74; 95% CI, 0.59-0.92) but had worse quality of life (β=-4.54; 95% CI, -6.40 to -2.68) than those without diabetes. Patients with diabetes were more likely to have cardiac (hypertension [OR, 3.04; 95% CI, 2.19-4.22], myocardial infarction [OR, 1.55; 95% CI, 1.18-2.03], heart failure [OR, 1.99; 95% CI, 1.57-2.51]) and neurological (stroke [OR, 1.39, 95% CI, 1.03-1.87], cognitive impairment [OR, 1.75, 95% CI, 1.39-2.21]) comorbidities. Conclusions Patients who have AF with diabetes less often perceive AF symptoms but have worse quality of life and more cardiac and neurological comorbidities than those without diabetes. This raises the question of whether patients with diabetes should be systematically screened for silent AF. Registration URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02105844.

Competing Interests: The authors declared no conflicts of interest.

Background & Aims: Dietary intake of several specific macronutrients has been linked to risk of coronary heart disease (CHD). However, these associations may depend on overall macronutrient composition rather than effects of one single macronutrient. Therefore, we aimed to investigate the associations of macronutrient intake and CHD and its related risk factors, by taking into account different macronutrient substitutions., Methods: This study was performed among 5873 participants from the Rotterdam Study, a population-based cohort study. Macronutrient intake was measured using a semi-quantitative food-frequency questionnaire. Cox proportional hazard regression analyses were used to examine associations between intakes of macronutrients and CHD incidence; and linear regression analyses were used to examine associations with the related risk factors, including triglycerides, total, high-density and low-density cholesterol levels, body mass index (BMI), fat mass index (FMI), and fat-free mass index (FFMI)., Results: We documented 669 CHD cases during 74,776 person-years of follow-up. In multivariable-adjusted models we observed no statistically significant associations between macronutrients and CHD incidence. Although non-significant, a higher plant protein intake tended to be associated with a lower risk of CHD when consumed at the expense of any of the other macronutrients. This association was strongest when 5% of energy (5 E%) of plant protein was consumed at the expense of animal protein (HR = 0.61; 95% CI 0.31, 1,21), mono- and disaccharides (HR = 0.62; 95% CI 0.29, 1.35) or saturated fat (HR = 0.61; 95% CI 0.31, 1.20). No consistent associations were observed for risk factors related to CHD., Conclusions: Macronutrient composition was not significantly associated with CHD incidence or cardiometabolic risk factors in an adult population. Future studies should further investigate food sources and quality of macronutrients., Competing Interests: Conflicts of interest None to declare., (Copyright © 2021. Published by Elsevier Ltd.)

Study Design: Systematic review and meta-analysis., Objective: To determine the difference in cardiovascular risk factors (blood pressure, lipid profile, and markers of glucose metabolism and inflammation) according to the neurological level of spinal cord injury (SCI)., Methods: We searched 5 electronic databases from inception until July 4, 2020. Data were extracted by two independent reviewers using a pre-defined data collection form. The pooled effect estimate was computed using random-effects models, and heterogeneity was calculated using I 2 statistic and chi-squared test (CRD42020166162)., Results: We screened 4863 abstracts, of which 47 studies with 3878 participants (3280 males, 526 females, 72 sex unknown) were included in the meta-analysis. Compared to paraplegia, individuals with tetraplegia had lower systolic and diastolic blood pressure (unadjusted weighted mean difference, -14.5 mmHg, 95% CI -19.2, -9.9; -7.0 mmHg 95% CI -9.2, -4.8, respectively), lower triglycerides (-10.9 mg/dL, 95% CI -19.7, -2.1), total cholesterol (-9.9 mg/dL, 95% CI -14.5, -5.4), high-density lipoprotein (-1.7 mg/dL, 95% CI -3.3, -0.2) and low-density lipoprotein (-5.8 mg/dL, 95% CI -9.0, -2.5). Comparing individuals with high- vs. low-thoracic SCI, persons with higher injury had lower systolic and diastolic blood pressure (-10.3 mmHg, 95% CI -13.4, -7.1; -5.3 mmHg 95% CI -7.5, -3.2, respectively), while no differences were found for low-density lipoprotein, serum glucose, insulin, and inflammation markers. High heterogeneity was partially explained by age, prevalent cardiovascular diseases and medication use, body mass index, sample size, and quality of studies., Conclusion: In SCI individuals, the level of injury may be an additional non-modifiable cardiovascular risk factor. Future well-designed longitudinal studies with sufficient follow-up and providing sex-stratified analyses should confirm our findings and explore the role of SCI level in cardiovascular health and overall prognosis and survival., (© 2021. The Author(s).)

Background: Psychiatric disorders constitute a major public health concern that are associated with substantial health and socioeconomic burden. Psychiatric patients may be more vulnerable to high temperatures, which under current climate change projections will most likely increase the burden of this public health concern., Objective: This study investigated the short-term association between ambient temperature and mental health hospitalizations in Bern, Switzerland., Methods: Daily hospitalizations for mental disorders between 1973 and 2017 were collected from the University Hospital of Psychiatry and Psychotherapy in Bern. Population-weighted daily mean ambient temperatures were derived for the catchment area of the hospital from 2.3-km gridded weather maps. Conditional quasi-Poisson regression with distributed lag linear models were applied to assess the association up to three days after the exposure. Stratified analyses were conducted by age, sex, and subdiagnosis, and by subperiods (1973-1989 and 1990-2017). Additional subanalyses were performed to assess whether larger risks were found during the warm season or were due to heatwaves., Results: The study included a total number of 88,996 hospitalizations. Overall, the hospitalization risk increased linearly by 4.0% (95% CI 2.0%, 7.0%) for every 10°C increase in mean daily temperature. No evidence of a nonlinear association or larger risks during the warm season or heatwaves was found. Similar estimates were found across for all sex and age categories, and larger risks were found for hospitalizations related to developmental disorders (29.0%; 95% CI 9.0%, 54.0%), schizophrenia (10.0%; 95% CI 4.0%, 15.0%), and for the later rather than the earlier period (5.0%; 95% CI 2.0%, 8.0% vs. 2.0%; 95% CI -3.0%, 8.0%)., Conclusions: Our findings suggest that increasing temperatures could negatively affect mental status in psychiatric patients. Specific public health policies are urgently needed to protect this vulnerable population from the effects of climate change., Competing Interests: The author TM is employed by Privatclinic Meiringen, Switzerland and the author AT is employed by the European Commission. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The views here expressed are those of the authors and do not necessarily reflect an official position of the European Commission. The authors have declared that no competing interests exist.

Observational studies suggest that early onset of menopause is associated with increased risk of hypertension. Whether this association is causal or due to residual confounding and/or reverse causation remains undetermined. We aimed to evaluate the observational and causal association between age at natural menopause (ANM) and blood pressure traits in Caucasian women. A cross-sectional and one-sample Mendelian randomization (MR) study was conducted in 4451 postmenopausal women from the CoLaus and Rotterdam studies. Regression models were built with observational data to study the associations of ANM with systolic and diastolic blood pressure (SBP/DBP) and hypertension. One-sample MR analysis was performed by calculating a genetic risk score of 54 ANM-related variants, previously identified in a genome-wide association study (GWAS) on ANM. In the two-sample MR analysis we used the estimates from the ANM-GWAS and association estimates from 168,575 women of the UK Biobank to evaluate ANM-related variants and their causal association with SBP and DBP. Pooled analysis from both cohorts showed that a one-year delay in menopause onset was associated with 2% (95% CI 0; 4) increased odds of having hypertension, and that early menopause was associated with lower DBP (β = -1.31, 95% CI -2.43; -0.18). While one-sample MR did not show a causal association between ANM and blood pressure traits, the two-sample MR showed a positive causal association of ANM with SBP; the last was driven by genes related to DNA damage repair. The present study does not support the hypothesis that early onset of menopause is associated with higher blood pressure. Our results suggest different ANM-related genetic pathways could differently impact blood pressure.

Objectives: Global environmental challenges demand sustainable behaviours and policies to protect human and planetary health. We aimed to summarize the evidence about the factors related to Sustainable Food Consumption (SFC) behaviours of university students, and to propose an operational categorization of SFC behaviours. Methods: Seven databases were searched for observational studies evaluating Sustainable Food Consumption (SFC) among university students and that reported at least one behavioural outcome measure. Qualitative synthesis was conducted, and PRISMA guidelines for reporting were followed. Results: Out of 4,479 unique references identified, 40 studies were selected. All studies examined personal factors, while 11 out of 40 also measured social or situational factors. Except for food waste, females had higher levels of SFC behaviours, but situational factors moderated this association. Knowledge and attitudes showed mixed results. Overall, sustainable food consumers reported healthier lifestyles. Conclusions: Healthy lifestyle of sustainable food consumers suggests possible synergies between human health and sustainability in terms of motivations for food choice. Moderation effects of social and situational factors on personal factors reveal opportunities to design and examine the effects of choice architecture interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Aguirre Sánchez, Roa-Díaz, Gamba, Grisotto, Moreno Londoño, Mantilla-Uribe, Rincón Méndez, Ballesteros, Kopp-Heim, Minder, Suggs and Franco.)

Background: Despite using identical evidence to support practice guidelines for lipid-lowering treatment in primary prevention of cardiovascular disease (CVD), it is unclear to what extent the 2018 American Heart Association/American College of Cardiology/Multisociety, 2016 US Preventive Services Task Force (USPSTF), 2020 Department of Veterans Affairs/Department of Defense, 2021 Canadian Cardiovascular Society, and 2019 European Society of Cardiology/European Atherosclerosis Society guidelines differ in grading and assigning levels of evidence and classes of recommendations (LOE/class) at a population level., Methods: We included 7262 participants, aged 45 to 75 years, without history of CVD from the prospective population-based Rotterdam Study. Per guideline, proportions of the population recommended statin therapy by LOE/class, sensitivity and specificity for CVD events, and numbers needed to treat at 10 years were calculated., Results: Mean age was 61.1 (SD 6.9) years; 58.2% were women. American Heart Association/American College of Cardiology/Multisociety, USPSTF, Department of Veterans Affairs/Department of Defense, Canadian Cardiovascular Society, and European Society of Cardiology/European Atherosclerosis Society strongly recommended statin initiation in respective 59.4%, 40.2%, 45.2%, 73.7%, and 42.1% of the eligible population based on high-quality evidence. Sensitivity for CVD events for treatment recommendations supported with strong LOE/class was 86.3% for American Heart Association/American College of Cardiology/Multisociety (IA or IB), 69.4% for USPSTF (USPSTF-B), 74.5% for Department of Veterans Affairs/Department of Defense (strong for), 93.3% for Canadian Cardiovascular Society (strong), and 66.6% for European Society of Cardiology/European Atherosclerosis Society (IA). Specificity was highest for the USPSTF at 45.3% and lowest for European Society of Cardiology/European Atherosclerosis Society at 10.0%. Estimated numbers needed to treat at 10 years for those with the strongest LOE/class were ranging from 20 to 26 for moderate-intensity and 12 to 16 for high-intensity statins., Conclusions: Sensitivity, specificity, and numbers needed to treat at 10 years for assigned LOE/class varied greatly among 5 CVD prevention guidelines. The level of variability seems to be driven by differences in how the evidence is graded and translated into LOE/class underlying the treatment recommendations by different professional societies. Efforts towards harmonizing evidence grading systems for clinical guidelines in primary prevention of CVD may reduce ambiguity and reinforce updated evidence-based recommendations.

Introduction: The COVID-19 pandemic has negatively impacted mental health. Up to a quarter of the population has reported mental health disorders. This has been studied mainly from a nosological perspective, according to diagnostic criteria. Nevertheless, we did not find studies that have explored the daily expressions of the population. Our objective was to evaluate the perceptions of the COVID-19 pandemic and its repercussions on the emotional well-being of the Colombian population., Methods: We performed a Twitter metrics and trend analysis. Initially, in the trend analysis, we calculated the average duration in hours of the 20 most popular trending topics of the day in Colombia and we grouped them into trends related to COVID-19 and unrelated trends. Subsequently, we identified dates of events associated with the pandemic relevant to the country, and they were related to the behaviour of the trends studied. Additionally, we did an exploratory analysis of these, selected the tweets with the greatest reach and categorised them in an inductive way to analyse them qualitatively., Results: Issues not related to COVID-19 were more far-reaching than those related to coronavirus. However, a rise in these issues was seen on some dates consistent with important events in Colombia. We found expressions of approval and disapproval, solidarity and accusation. Inductively, we identified categories of informative tweets, humour, fear, stigma and discrimination, politics and entities, citizen complaints, and self-care and optimism., Conclusions: The impact of the COVID-19 pandemic generates different reactions in the population, which increasingly have more tools to express themselves and know the opinions of others. Social networks play a fundamental role in the communication of the population, so this content could serve as a public health surveillance tool and a useful and accessible means of communication in the management of health crises., (Copyright © 2021 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Purpose: Cardiovascular disease (CVD) is a leading cause of mortality globally and is strongly influenced by dietary risk factors. The aim was to assess the association between egg consumption and risk of CVD risk/mortality, including coronary heart disease (CHD), stroke, and heart failure., Methods: MEDLINE, Embase, and Web of Science databases were searched through April 2020 for prospective studies. Two independent reviewers screened and extracted the data through standardized methods. Size effects were calculated as summary relative risks (SRRs) in a dose-response fashion through random-effects meta-analyses., Results: Thirty-nine studies including nearly 2 million individuals and 85,053 CHD, 25,103 stroke, 7536 heart failure, and 147,124 CVD cases were included. The summary analysis including 17 datasets from 14 studies conducted on CVD (incidence and/or mortality) showed that intake of up to six eggs per week is inversely associated with CVD events, when compared to no consumption [for four eggs per week, SRR = 0.95 (95% CI: 0.90; 1.00)]; a decreased risk of CVD incidence was observed for consumption of up to one egg per day [SRR = 0.94 (95% CI: 0.89; 0.99)]. The summary analysis for CHD incidence/mortality including 24 datasets from 16 studies showed a decreased risk up to two eggs per week [(SRR = 0.96 (95% CI: 0.91; 1.00)]. No associations were retrieved with risk of stroke. The summary analysis for heart failure risk including six datasets from four studies showed that intake of one egg per day was associated with increased risk raising for higher intakes compared to no consumption [for 1 egg per day, SRR = 1.15 (95% CI:1.02; 1.30)]. After considering GRADE criteria for strength of the evidence, it was rated low for all outcomes but stroke, for which it was moderate (yet referring to no risk)., Conclusion: There is no conclusive evidence on the role of egg in CVD risk, despite the fact that higher quality studies are warranted to obtain stronger evidence for a possible protection of CVD associated with moderate weekly egg consumption compared to no intake; equally, future studies may strengthen the evidence for increased heart failure risk associated with high regular egg consumption.

We conducted genome-wide association studies (GWAS) of relative intake from the macronutrients fat, protein, carbohydrates, and sugar in over 235,000 individuals of European ancestries. We identified 21 unique, approximately independent lead SNPs. Fourteen lead SNPs are uniquely associated with one macronutrient at genome-wide significance (P < 5 × 10 -8 ), while five of the 21 lead SNPs reach suggestive significance (P < 1 × 10 -5 ) for at least one other macronutrient. While the phenotypes are genetically correlated, each phenotype carries a partially unique genetic architecture. Relative protein intake exhibits the strongest relationships with poor health, including positive genetic associations with obesity, type 2 diabetes, and heart disease (r g ≈ 0.15-0.5). In contrast, relative carbohydrate and sugar intake have negative genetic correlations with waist circumference, waist-hip ratio, and neighborhood deprivation (|r g | ≈ 0.1-0.3) and positive genetic correlations with physical activity (r g ≈ 0.1 and 0.2). Relative fat intake has no consistent pattern of genetic correlations with poor health but has a negative genetic correlation with educational attainment (r g ≈-0.1). Although our analyses do not allow us to draw causal conclusions, we find no evidence of negative health consequences associated with relative carbohydrate, sugar, or fat intake. However, our results are consistent with the hypothesis that relative protein intake plays a role in the etiology of metabolic dysfunction., (© 2020. The Author(s).)

Background: Thyroid hormones are important metabolic regulators exerting effects in multiple systemic functions including muscular and cardiorespiratory function. Thyroid hormones may influence physical activity levels. However, there are currently no studies evaluating the association between thyroid function and physical activity levels in the general population. Methods: In a population-based cohort study between 2006 and 2013, we assessed the cross-sectional and longitudinal (with a mean follow-up time of 5 years) association of serum thyrotropin (TSH) and free thyroxine (fT4) with physical activity (metabolic equivalent task [MET] hours per week). Information on physical activity was collected using a validated questionnaire (Longitudinal Aging Study Amsterdam, median 22.50 MET hours per week). The association of TSH and fT4 with physical activity was examined using linear regression models in the cross-sectional and longitudinal analyses, adjusted for age, sex, lifestyle factors, and cardiovascular disease. In sensitivity analyses, we examined the association between thyroid function and physical activity including only participants within the reference range of thyroid function. We additionally examined moderate and vigorous physical activity separately as outcomes. Results: We included 2470 participants for the cross-sectional analysis (mean age 57.3 years, 58% women) and 1907 participants for the longitudinal analysis (mean age 56.9 years). There was no association between TSH (mIU/L) or fT4 (ng/dL) and physical activity ( β  = 0.65, 95% confidence interval [CI, -1.67 to 2.98] and β  = 2.76, [CI -7.15 to 12.66], respectively) on cross-sectional analysis. Similarly, in the longitudinal analyses, we observed no association of TSH ( β  = 1.16, [CI -1.31 to 3.63]) or fT4 ( β  = -6.63, [CI -17.06 to 3.80]) with physical activity. Conclusions: We did not observe an association between the endogenous thyroid hormone level and total physical activity. Further studies need to be performed to evaluate whether thyroid hormone replacement therapy is associated with physical activity.

Background: Adherence to a healthy diet could contribute to maintaining adequate health throughout the menopausal transition, but data are scarce., Objective: We evaluated the association between menopausal status and changes in dietary intake in Swiss adult women., Methods: Cross-sectional (n = 2439) and prospective analyses (n = 1656) were conducted between 2009 and 2012 (first follow-up) among women (mean age ± SD, 58.2 ± 10.5 y) living in Lausanne, Switzerland. In both visits, dietary intake was assessed using a validated FFQ, and menopausal status was classified based on the presence or absence of menstruations. Multivariable linear and logistic regression models were used to investigate the cross-sectional association of menopausal status (postmenopausal compared with premenopausal) at the first follow-up with food intake and dietary recommendations. To examine whether menopausal status (premenopausal as reference group, menopausal transition, and postmenopausal) during 5 y of follow-up was associated with longitudinal changes in diet, including adherence to dietary Swiss recommendations, we applied multivariable linear and logistic mixed models adjusted for several covariates., Results: At the first follow-up, postmenopausal women consumed less (P < 0.002) meat [median (IQR) 57.2 (35-86.2) compared with 62.5 (41.2-95.2) g/d], pasta [61.8 (37.5-89.2) compared with 85 (57.8-128) g/d], and added sugar [0.1 (0-4) compared with 0.7 (0-8) g/d] and more dairy products [126 (65.4-214) compared with 109 (64.5-182) g/d] and fruit [217 (115-390) compared with 174 (83.2-319) g/d] than premenopausal women. However, linear regression analysis adjusted for potential confounding factors showed no independent (cross-sectional) associations of menopausal status with total energy intake (TEI) and individual macro- or micronutrient intakes. In the prospective analysis, compared with women who remained premenopausal during follow-up (n = 244), no differences were found in changes in TEI, dietary intakes, or adherence to the Swiss dietary recommendations in women transitioning from premenopausal to postmenopausal (n = 229) and who remained postmenopausal (n = 1168)., Conclusion: The menopausal transition is not associated with changes in dietary habits among Swiss women., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Competing Interests: We declare no competing interests. The authors would like to acknowledge the work of Stevan Stojic in providing the graphic illustrations of the framework.

New gridded climate datasets (GCDs) on spatially resolved modeled weather data have recently been released to explore the impacts of climate change. GCDs have been suggested as potential alternatives to weather station data in epidemiological assessments on health impacts of temperature and climate change. These can be particularly useful for assessment in regions that have remained understudied due to limited or low quality weather station data. However to date, no study has critically evaluated the application of GCDs of variable spatial resolution in temperature-mortality assessments across regions of different orography, climate, and size. Here we explored the performance of population-weighted daily mean temperature data from the global ERA5 reanalysis dataset in the 10 regions in the United Kingdom and the 26 cantons in Switzerland, combined with two local high-resolution GCDs (HadUK-grid UKPOC-9 and MeteoSwiss-grid-product, respectively) and compared these to weather station data and unweighted homologous series. We applied quasi-Poisson time series regression with distributed lag nonlinear models to obtain the GCD- and region-specific temperature-mortality associations and calculated the corresponding cold- and heat-related excess mortality. Although the five exposure datasets yielded different average area-level temperature estimates, these deviations did not result in substantial variations in the temperature-mortality association or impacts. Moreover, local population-weighted GCDs showed better overall performance, suggesting that they could be excellent alternatives to help advance knowledge on climate change impacts in remote regions with large climate and population distribution variability, which has remained largely unexplored in present literature due to the lack of reliable exposure data., Competing Interests: The authors declare no conflicts of interest relevant to this study., (© 2021. The Authors.)

Sarcopenia is a heterogeneous skeletal muscle disorder involving the loss of muscle mass and function. However, the prevalence of sarcopenia based on the most recent definition remains to be determined in older people with chronic airway diseases. The aim was to evaluate sarcopenia prevalence and association with chronic airway diseases and its lung function in an older population, using the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. We performed a cross-sectional analysis in 5082 participants (mean age 69.0±8.8 years, 56% females) from the Rotterdam Study. Participants with interpretable spirometry and an available assessment of sarcopenia were included. The appendicular skeletal muscle mass index (ASMI) and handgrip strength (HGS) were assessed using dual-energy X-ray absorptiometry (DXA) and a hydraulic hand dynamometer, respectively. We analysed the association between sarcopenia and chronic airway diseases by using regression models adjusted for age, sex, smoking status, total fat percentage and other relevant confounders. Participants with chronic airway diseases had higher prevalence of probable sarcopenia (12.0%, 95% CI 10.2-13.8) and confirmed sarcopenia (3.0%, 95% CI 2.1-3.9) than without. Chronic airway diseases were associated with "probable sarcopenia" (OR 1.28, 95% CI 1.02-1.60), "confirmed sarcopenia" (OR 2.13, 95% CI 1.33-3.43), reduced HGS (β -0.51 (-0.90--0.11)) and reduced ASMI (β -0.19 (-0.25--0.14)). Forced expiratory volume in 1 s <80% was associated with lower HGS (β -1.03 (-1.75--0.31)) and lower ASMI (β -0.25 (-0.36--0.15)) than forced expiratory volume in 1 s ≥80%. Sarcopenia was prevalent and associated with chronic airway diseases among older population. These results suggest the need for early diagnosis of sarcopenia in older people with chronic airway diseases by applying EWGSOP2 recommendations., Competing Interests: Conflict of interest: E. Benz has nothing to disclose. Conflict of interest: K. Trajanoska has nothing to disclose. Conflict of interest: J.D. Schoufour has nothing to disclose. Conflict of interest: L. Lahousse reports awards sponsored by AstraZeneca and Chiesi, and expert consultation for Boehringer Ingelheim GmbH and Novartis, outside the submitted work. Conflict of interest: E.W. de Roos has nothing to disclose. Conflict of interest: N. Terzikhan has nothing to disclose. Conflict of interest: C. Medina-Gomez has nothing to disclose. Conflict of interest: K. Verhamme works for a research group that received/receives research grants from Yamanouchi, Pfizer/BI, Novartis and GSK, none of which are related to the content of this work. Conflict of interest: R. Williams has nothing to disclose. Conflict of interest: B.H. Stricker has nothing to disclose. Conflict of interest: O.H. Franco has nothing to disclose. Conflict of interest: M.A. Ikram has nothing to disclose. Conflict of interest: F. Rivadeneira has nothing to disclose. Conflict of interest: G. Brusselle has nothing to disclose., (Copyright ©ERS 2021.)

In May 2020, Latin America became the epicenter of the COVID-19 pandemic, a region already afflicted by social disparities, poor healthcare access, inadequate nutrition and a large prevalence of noncommunicable chronic diseases. Obesity and its comorbidities are increasingly prevalent in Latin America, with a more rapid growth in individuals with lower income, and currently a disease associated with COVID-19 severity, complications and death. In this document, the Latin American Association of Obesity Societies and collaborators present a review of the burden of two pandemics in Latin America, discuss possible mechanisms that explain their relationship with each other and provide public health and individual recommendations, as well as questions for future studies., (© 2020 World Obesity Federation.)

Background: Although it is well acknowledged that psychosocial risk factors (PSRF) such as low socio-economic status, stress, social isolation, negative emotions and negative personality patterns may contribute to the development and adverse outcome of cardiovascular disease (CVD), screening for PSRF in CVD patients is usually limited to anxiety and depression, mainly for feasibility reasons. We therefore aimed to develop a user-friendly screening battery for routine assessment of PSRFs and to evaluate this instrument regarding feasibility of application, PSRF results and attendance of psychological counselling if recommended to cardiac rehabilitation (CR) patients., Methods: This is a prospective single center cohort study including 609 consecutive CR patients. We first developed a screening instrument based on seven validated scales for the most relevant PSRFs with totally 90 questions presented in a uniform graphical design to facilitate completion called Psychocardiogram® (PCG) and applied the instrument in consecutive patients attending CR. Patients with positive screening results were invited to a psychological counseling session., Results: Six hundred and nine consecutive patients, aged 34 to 86 years (mean 60.7 years), 85% men, entering the CR program at the Bern University Hospital with ischemic heart failure (CHF), coronary artery disease (CAD) or peripheral artery disease, were included in this study. Eighty-three point three percent of the patients completed the PCG within 40 minutes. Vital exhaustion and Type-D personality were the most prevalent PSRFs (56.9% and 51.1%, respectively), whereas low social support (14.4%) and elevated depressive symptoms (15.9%), were the least prevalent ones. After screening, 120 patients (52.86%) with at least one PSRF made use of psychological counseling., Conclusions: We found the PCG to be a useful screening tool for PSRF in CR patients with the potential to get new insights into the prevalence of particular PSRF in specific populations and to better study their impact on occurrence and outcome of CVD., Competing Interests: The authors have no competing interest to declare., (Copyright: © 2021 The Author(s).)

Health-care workers (HCWs) are at the frontline of response to coronavirus disease 2019 (COVID-19), being at a higher risk of acquiring the disease and, subsequently, exposing patients and others. Searches of 8 bibliographic databases were performed to systematically review the evidence on the prevalence, risk factors, clinical characteristics, and prognosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among HCWs. A total of 97 studies (all published in 2020) met the inclusion criteria. The estimated prevalence of SARS-CoV-2 infection from HCWs' samples, using reverse transcription-polymerase chain reaction and the presence of antibodies, was 11% (95% confidence interval (CI): 7, 15) and 7% (95% CI: 4, 11), respectively. The most frequently affected personnel were nurses (48%, 95% CI: 41, 56), whereas most of the COVID-19-positive medical personnel were working in hospital nonemergency wards during screening (43%, 95% CI: 28, 59). Anosmia, fever, and myalgia were the only symptoms associated with HCW SARS-CoV-2 positivity. Among HCWs positive for COVID-19 by reverse transcription-polymerase chain reaction, 40% (95% CI: 17, 65) were asymptomatic at time of diagnosis. Finally, severe clinical complications developed in 5% (95% CI: 3, 8) of the COVID-19-positive HCWs, and 0.5% (95% CI: 0.02, 1.3) died. Health-care workers suffer a significant burden from COVID-19, with those working in hospital nonemergency wards and nurses being the most commonly infected personnel., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We aimed to obtain reliable reference charts for sleep duration, estimate the prevalence of sleep complaints across the lifespan and identify risk indicators of poor sleep. Studies were identified through systematic literature search in Embase, Medline and Web of Science (9 August 2019) and through personal contacts. Eligible studies had to be published between 2000 and 2017 with data on sleep assessed with questionnaires including ≥100 participants from the general population. We assembled individual participant data from 200,358 people (aged 1-100 years, 55% female) from 36 studies from the Netherlands, 471,759 people (40-69 years, 55.5% female) from the United Kingdom and 409,617 people (≥18 years, 55.8% female) from the United States. One in four people slept less than age-specific recommendations, but only 5.8% slept outside of the 'acceptable' sleep duration. Among teenagers, 51.5% reported total sleep times (TST) of less than the recommended 8-10 h and 18% report daytime sleepiness. In adults (≥18 years), poor sleep quality (13.3%) and insomnia symptoms (9.6-19.4%) were more prevalent than short sleep duration (6.5% with TST < 6 h). Insomnia symptoms were most frequent in people spending ≥9 h in bed, whereas poor sleep quality was more frequent in those spending <6 h in bed. TST was similar across countries, but insomnia symptoms were 1.5-2.9 times higher in the United States. Women (≥41 years) reported sleeping shorter times or slightly less efficiently than men, whereas with actigraphy they were estimated to sleep longer and more efficiently than man. This study provides age- and sex-specific population reference charts for sleep duration and efficiency which can help guide personalized advice on sleep length and preventive practices.

Background: Obesity and metabolic syndrome (MetS) are key risk factors for type 2 diabetes and cardiovascular disease. Little information exists on the prevalence of obesity and MetS in Latin America and specifically in Ecuador. We aimed to estimate the prevalence of overweight, obesity, and MetS among adults in Ecuador., Methods: We analyzed data from a nation-wide population-based survey in Ecuador (ENSANUT-ECU) among 10,318 participants (3684 men, 6634 women; age range: 18-59 years) conducted in 2012. Data related to residential location (urban versus rural), altitude (< 500, 500-1500 or > 1500 m above sea level (MASL)), region (highland, coast, amazon, or Galápagos), and socioeconomic status were collected. BMI, waist circumference, blood lipids, glucose, and blood pressure were measured by trained fieldworkers following standardized procedures., Results: The age-standardized prevalence of overweight was 39.5%; 22.3% was obese; and 31.2% had MetS. The prevalence of obesity, low HDL-cholesterol, and abdominal obesity were higher in women than in men, whereas men had a higher prevalence of hypertension (p < 0.05). Sex differences were not observed regarding the prevalence of combined MetS. Prevalence of both obesity and MetS was higher in urban areas, at low altitude regions (coast and Galapagos), and at high socioeconomic status (all p < 0.05)., Conclusions: Prevalence of obesity and MetS in Ecuador are high. There are important demographic differences in the prevalence of MetS between Ecuadorian subpopulations that requires targeted research and prevention efforts, to hold and reduce the current public health problem of metabolic disorders.

Background: Genome-wide association studies have identified multiple genomic loci associated with coronary artery disease, but most are common variants in non-coding regions that provide limited information on causal genes and etiology of the disease. To overcome the limited scope that common variants provide, we focused our investigation on low-frequency and rare sequence variations primarily residing in coding regions of the genome., Methods and Results: Using samples of individuals of European ancestry from ten cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, both cross-sectional and prospective analyses were conducted to examine associations between genetic variants and myocardial infarction (MI), coronary heart disease (CHD), and all-cause mortality following these events. For prevalent events, a total of 27,349 participants of European ancestry, including 1831 prevalent MI cases and 2518 prevalent CHD cases were used. For incident cases, a total of 55,736 participants of European ancestry were included (3,031 incident MI cases and 5,425 incident CHD cases). There were 1,860 all-cause deaths among the 3,751 MI and CHD cases from six cohorts that contributed to the analysis of all-cause mortality. Single variant and gene-based analyses were performed separately in each cohort and then meta-analyzed for each outcome. A low-frequency intronic variant (rs988583) in PLCL1 was significantly associated with prevalent MI (OR = 1.80, 95% confidence interval: 1.43, 2.27; P = 7.12 × 10-7). We conducted gene-based burden tests for genes with a cumulative minor allele count (cMAC) ≥ 5 and variants with minor allele frequency (MAF) < 5%. TMPRSS5 and LDLRAD1 were significantly associated with prevalent MI and CHD, respectively, and RC3H2 and ANGPTL4 were significantly associated with incident MI and CHD, respectively. No loci were significantly associated with all-cause mortality following a MI or CHD event., Conclusion: This study identified one known locus (ANGPTL4) and four new loci (PLCL1, RC3H2, TMPRSS5, and LDLRAD1) associated with cardiovascular disease risk that warrant further investigation., Competing Interests: BMP reports serving service on the DSMB of a clinical trial funded by the manufacturer (Zoll LifeCor) and on the Steering Committee of the Yale Open Data Access Project. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: To examine the impact of combined lifestyle factors on premature mortality and life expectancy in Chinese adults., Methods: A total of 44,052 Chinese adults aged 45-74 years free of cardiovascular disease (CVD), cancer, and diabetes were followed from recruitment (1993-1998) to the end of 2016 in the Singapore Chinese Health Study. A composite score (0-5 scale) was calculated based on five baseline healthy lifestyle factors including healthy diet, nonsmoking status, light to moderate alcohol drinking, being physically active and optimal body mass index. Mortality cases were identified through linkage with the nationwide death registry., Results: Adopting five healthy versus none was associated with a lower risk of all-cause and cause-specific mortality, and the hazard ratio (95% confidence interval [CI]) was 0.38 (0.29, 0.51) for all-cause mortality, 0.26 (0.13, 0.52) for CVD mortality, and 0.59 (0.37, 0.92) for cancer mortality. Nonadherence to 4-5 healthy lifestyle factors accounted for 34.9% (95% CI = 29.2, 40.2) in population attributable fraction for all-cause mortality, 35.1% (23.7, 44.9) for CVD mortality, and 18.0% (6.5, 28.0) for cancer mortality. Conversely, adherence to 4-5 healthy lifestyle factors versus none could achieve a gain of 8.1 years in women and 6.6 years in men for the life expectancy at 50 years., Conclusions: A healthier lifestyle is associated with a substantially reduced risk of mortality and a longer life expectancy in the Chinese population. Our findings highlight the necessity of coordinated actions targeting combined lifestyle factors in reducing the overall burden of diseases and premature deaths., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To investigate the longitudinal association between the macronutrient composition of the diet and frailty., Methods: Data were obtained from 5205 Dutch middle-aged and older adults participating in the Rotterdam Study. Frailty was measured using a frailty index based on the accumulation of 38 health-related deficits, score between 0 and 100, and a higher score indicating more frailty. Frailty was assessed at baseline and 11 years later (range of 23 years). Macronutrient intake was assessed using food-frequency questionnaires. The association between macronutrients and frailty over time was evaluated using multivariable linear regression, adjusted for the frailty index at baseline, energy intake, and other relevant confounders. All analyses were performed in strata of BMI., Results: Median frailty index score was 13.8 points (IQR 9.6; 19.1) at baseline and increased by a median of 2.3 points (IQR - 2.0; 7.6) after 11 years. Overall, we found no significant associations between intake of carbohydrates or fat and frailty over time. We did observe a significant positive association between an iso-energetic intake of 10 g protein and frailty over time (β 0.31 (95% CI 0.06; 0.55)) which was mainly driven by animal protein (β 0.31 (95% CI 0.07; 0.56)). It did not depend on whether it was substituted fat or carbohydrates., Conclusions: Our findings suggest that a reduction in the intake of animal protein may improve the overall health status over time in a relatively healthy population. More research is needed on the optimal macronutrient composition of the diet and frailty in more vulnerable populations.

Introduction: Associations between time spent on physical activity, sedentary behavior, and sleep and quality of life are usually studied without considering that their combined time is fixed. This study investigates the reallocation of time spent on physical activity, sedentary behavior, and sleep during the 24-hour day and their associations with quality of life., Methods: Data from the 2011-2016 Rotterdam Study were used to perform this cross-sectional analysis among 1,934 participants aged 51-94 years. Time spent in activity levels (sedentary, light-intensity physical activity, moderate-to-vigorous physical activity, and sleep) were objectively measured with a wrist-worn accelerometer combined with a sleep diary. Quality of life was measured using the EuroQoL 5D-3L questionnaire. The compositional isotemporal substitution method was used in 2018 to examine the association between the distribution of time spent in different activity behaviors and quality of life., Results: Reallocation of 30 minutes from sedentary behavior, light-intensity physical activity, or sleep to moderate-to-vigorous physical activity was associated with a higher quality of life, whereas reallocation from moderate-to-vigorous physical activity to sedentary behavior, light-intensity physical activity, or sleep was associated with lower quality of life. To illustrate this, a reallocation of 30 minutes from sedentary behavior to moderate-to-vigorous physical activity was associated with a 3% (95% CI=2, 4) higher quality of life score. By contrast, a reallocation of 30 minutes from moderate-to-vigorous physical activity to sedentary behavior was associated with a 4% (95% CI=2, 6) lower quality of life score., Conclusions: Moderate-to-vigorous physical activity is important with regard to the quality of life of middle-aged and elderly individuals. The benefits of preventing less time spent in moderate-to-vigorous physical activity were greater than the benefits of more time spent in moderate-to-vigorous physical activity. These results could shift the attention to interventions focused on preventing reductions in moderate-to-vigorous physical activity levels. Further longitudinal studies are needed to confirm these findings and explore causality., (Copyright © 2020 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Use of implantable cardioverter defibrillators is increasingly common. As patients approach the end of life, it is appropriate to deactivate the shock function., Aim: To assess the prevalence of implantable cardioverter defibrillator reprogramming to deactivate the shock function at the end of life and the prevalence of advance directives among this population., Design: Following a previously established protocol available in PROSPERO, we performed a narrative synthesis of our findings and used the logit transformation method to perform our quantitative synthesis., Data Sources: We searched seven bibliographic databases (Embase, Cochrane Central register of controlled Trials, Medline-Ovid, Web-of-Science, Scopus, PsychInfo, and CINAHL) and additional sources until April 2019., Results: Of the references we identified, 14 were included. We found a pooled prevalence of implantable cardioverter defibrillator reprogramming at the end of life of 28% (95% confidence interval, 22%-36%) with higher reprogramming rates after the recommendations for managing the device at the end of life were published. Among patients with advance directives, the pooled prevalence of advance directives that explicitly mentioned the device was 1% (95% confidence interval, 1%-3%)., Conclusions: The prevalence of implantable cardioverter defibrillator reprogramming and advance directives that explicitly mentioned the device was very low. Study data suggested reprogramming decisions were made very late, after the patient experienced multiple shocks. Patient suffering could be ameliorated if physicians and other healthcare professionals adhere to clinical guidelines for the good management of the device at the end of life and include deactivating the shock function in the discussion that leads to the advance directive.

Importance: Phytoestrogens are becoming popular constituents of human diets and are increasingly used by postmenopausal women., Objective: Our study aims to determine the effects of phytoestrogen supplementation on intermediate cardiovascular disease (CVD) risk factors in postmenopausal women., Evidence Review: Five electronic databases (Medline, EMBASE, Web of Science, Cochrane CENTRAL, Google Scholar) were systematically searched to identify eligible studies, that is, randomized controlled trials (RCTs) that assessed the association of phytoestrogen supplementation with CVD risk factors (serum lipids, homocysteine, fibrinogen, markers of inflammation, oxidative stress and endothelial function, carotid intima-media thickness [CIMT]) in postmenopausal women. Data were extracted by two independent reviewers using a predefined data collection form., Findings: In total, 56 RCTs were identified, including 4,039 individual postmenopausal women. There was substantial heterogeneity in quality across studies. Twenty-six (46%) RCTs showed poor quality and there was an indication of publication bias presence for some of the biomarkers. Results are reported in pooled mean difference (95% CI) of changes. Use of phytoestrogens was associated with a decrease in serum total cholesterol (-0.27 mmol/L [-0.41 to -0.13]), low-density lipoprotein (-0.25 mmol/L [-0.37 to -0.13]), triglycerides (-0.20 mmol/L [-0.28 to -0.11]), and apolipoprotein B (-0.13 g/L [-0.23 to -0.03]) and with an increase in serum apolipoprotein A-1 (0.04 g/L [0.02-0.07]. Also, phytoestrogen supplementation was associated with a decrease in serum intercellular adhesion molecule 1 (-18.86 ng/mL [-30.06 to -7.65]) and E-selectin (-2.32 ng/mL [-4.05 to -0.59]). There was no association observed between phytoestrogen supplementation and inflammatory markers, fibrinogen, homocysteine, or other endothelial function markers. In contrast, use of phytoestrogens was associated with an increase in CIMT (9.34 μm [95% CI, 0.39-18.29]). Effect estimates of phytoestrogen supplementation on oxidative stress could not be pooled., Conclusions and Relevance: Phytoestrogen supplementation seems to modestly improve the CVD risk profile of postmenopausal women by influencing blood lipids and parameters of endothelial function. In women with an increased risk of atherosclerosis, although modest, a harmful effect on CIMT progression may be present. Because of limited quality and the heterogeneous nature of the current evidence, additional rigorous studies are needed to explore the role of phytoestrogens in menopausal cardiovascular health. : Video Summary: http://links.lww.com/MENO/A593.

Iron metabolism and anemia may play an important role in multiple organ dysfunction syndrome in Coronavirus disease 2019 (COVID-19). We conducted a systematic review and meta-analysis to evaluate biomarkers of anemia and iron metabolism (hemoglobin, ferritin, transferrin, soluble transferrin receptor, hepcidin, haptoglobin, unsaturated iron-binding capacity, erythropoietin, free erythrocyte protoporphyrine, and erythrocyte indices) in patients diagnosed with COVID-19, and explored their prognostic value. Six bibliographic databases were searched up to August 3rd 2020. We included 189 unique studies, with data from 57,563 COVID-19 patients. Pooled mean hemoglobin and ferritin levels in COVID-19 patients across all ages were 129.7 g/L (95% Confidence Interval (CI), 128.51; 130.88) and 777.33 ng/mL (95% CI, 701.33; 852.77), respectively. Hemoglobin levels were lower with older age, higher percentage of subjects with diabetes, hypertension and overall comorbidities, and admitted to intensive care. Ferritin level increased with older age, increasing proportion of hypertensive study participants, and increasing proportion of mortality. Compared to moderate cases, severe COVID-19 cases had lower hemoglobin [weighted mean difference (WMD), - 4.08 g/L (95% CI - 5.12; - 3.05)] and red blood cell count [WMD, - 0.16 × 10 12 /L (95% CI - 0.31; - 0.014)], and higher ferritin [WMD, - 473.25 ng/mL (95% CI 382.52; 563.98)] and red cell distribution width [WMD, 1.82% (95% CI 0.10; 3.55)]. A significant difference in mean ferritin levels of 606.37 ng/mL (95% CI 461.86; 750.88) was found between survivors and non-survivors, but not in hemoglobin levels. Future studies should explore the impact of iron metabolism and anemia in the pathophysiology, prognosis, and treatment of COVID-19.

In low and middle-income countries (LMICs), strict social distancing measures (e.g., nationwide lockdown) in response to the COVID-19 pandemic are unsustainable in the long-term due to knock-on socioeconomic and psychological effects. However, an optimal epidemiology-focused strategy for 'safe-reopening' (i.e., balancing between the economic and health consequences) remain unclear, particularly given the suboptimal disease surveillance and diagnostic infrastructure in these settings. As the lockdown is now being relaxed in many LMICs, in this paper, we have (1) conducted an epidemiology-based "options appraisal" of various available non-pharmacological intervention options that can be employed to safely lift the lockdowns (namely, sustained mitigation, zonal lockdown and rolling lockdown strategies), and (2) propose suitable application, pre-requisites, and inherent limitations for each measure. Among these, a sustained mitigation-only approach (adopted in many high-income countries) may not be feasible in most LMIC settings given the absence of nationwide population surveillance, generalised testing, contact tracing and critical care infrastructure needed to tackle the likely resurgence of infections. By contrast, zonal or local lockdowns may be suitable for some countries where systematic identification of new outbreak clusters in real-time would be feasible. This requires a generalised testing and surveillance structure, and a well-thought out (and executed) zone management plan. Finally, an intermittent, rolling lockdown strategy has recently been suggested by the World Health Organization as a potential strategy to get the epidemic under control in some LMI settings, where generalised mitigation and zonal containment is unfeasible. This strategy, however, needs to be carefully considered for economic costs and necessary supply chain reforms. In conclusion, while we propose three community-based, non-pharmacological options for LMICs, a suitable measure should be context-specific and based on: (1) epidemiological considerations, (2) social and economic costs, (3) existing health systems capabilities and (4) future-proof plans to implement and sustain the strategy.

Background: Fibrotic diseases have an unclear etiology and poor prognosis. Fluctuations in thyroid function may play a role in the development of fibrosis, but evidence is fragmented and inconclusive. This systematic review and meta-analysis aimed to investigate the association of thyroid function with fibrotic diseases of the liver, heart, and lung in humans. Methods: We searched PubMed, Medline Ovid, Embase Ovid, and Web-of-Science for studies published from inception to 14 June 2019, to identify observational studies that investigated the association of thyroid function with fibrosis of the liver, heart, and lung in humans. Study quality was evaluated by the Newcastle-Ottawa Scale. The Mantel-Haenszel method was used to pool the odds ratios (ORs) of studies investigating the association of hypothyroidism with liver fibrosis. Results: Of the 2196 identified articles, 18 studies were included in the systematic review, of which 11 studies reported on liver fibrosis, 4 on myocardial fibrosis, and 3 on pulmonary fibrosis. The population sample size ranged from 36 to 7259 subjects, with median mean age 51 years (range, 36-69) and median percentage of women 53 (range, 17-100). The risk of bias of studies was low to moderate to high. Higher serum thyrotropin and lower thyroid hormone levels were generally associated with higher likelihood of fibrosis. Compared with euthyroidism, overt and subclinical hypothyroidism was associated with a higher likelihood of fibrosis in the liver (six of seven studies), heart (three of three studies), and lung (three of three studies). Based on the results of the seven studies included in the meta-analysis, overt and subclinical hypothyroidism was associated with an increased risk of liver fibrosis (pooled OR, 2.81; 95% confidence interval [CI], 1.74-4.53; heterogeneity, I 2 31.4%; pooled OR, 2.12; CI, 1.45-3.12; heterogeneity, I 2 0%; respectively), without evidence of publication bias. Conclusions: This study suggests that low thyroid function is associated with increased likelihood of chronic fibrotic diseases of the liver, heart, and lung. However, the evidence is mainly based on cross-sectional data. Prospective studies and randomized clinical trials are needed to investigate the potential efficacy of thyroid hormone and its analogs on the occurrence and progression of fibrosis.

Objective: People with diabetes show great variability in weight gain and duration of obesity at the time of diagnosis. BMI trajectories and other cardiometabolic risk factors prior to type 2 diabetes were investigated., Methods: A total of 6,223 participants from the Rotterdam Study cohort were included. BMI patterns before diagnosis of diabetes were identified through latent class trajectories., Results: During a mean follow-up of 13.7 years, 565 participants developed type 2 diabetes. Three distinct trajectories of BMI were identified, including the "progressive overweight" group (n = 481, 85.1%), "progressive weight loss" group (n = 59, 10.4%), and "persistently high BMI" group (n = 25, 4.4%). The majority, the progressive overweight group, was characterized by a steady increase of BMI in the overweight range 10 years before diabetes diagnosis. The progressive weight loss group had fluctuations of glucose and marked beta cell function loss. The persistently high BMI group was characterized by a slight increase in insulin levels and sharp increase of insulin resistance accompanied by a rapid decrease of beta cell function., Conclusions: Heterogeneity of BMI changes prior to type 2 diabetes was found in a middle-aged and elderly white population. Prevention strategies should be tailored rather than focusing only on high-risk individuals., (© 2020 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society (TOS).)

The zoonotic virus now named SARS-CoV-2 first infected humans in China, and COVID-19 has rapidly become pandemic. To mitigate its impact on societies, health systems and economies, countries have adopted non-pharmacological preventive practices such as 'spatial' or 'social' distancing, the use of protective masks, and handwashing; these have been widely implemented. However, measures aimed at protecting physical health and healthcare systems have side-effects that might have a big impact on individuals' wellbeing. As the pandemic reaches low- and middle-income countries, weaker health systems, limited resources and the lower socioeconomic status of their populations make halting the pandemic more challenging. In this article, we explore the impact of COVID-19 and its prevention measures on the wellbeing of vulnerable populations. Special attention must be given to homeless, indigenous, migrant and imprisoned populations, as well as people living with disabilities and the elderly. More than just resolute governmental action will be required to overcome the pandemic. Links between science and political actions have to be strengthened. Fighting COVID-19 is a collective endeavour and community action, on a global scale, is of paramount importance., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Since the placenta also has a sex, fetal sex-specific differences in the occurrence of placenta-mediated complications could exist., Objective: To determine the association of fetal sex with multiple maternal pregnancy complications., Search Strategy: Six electronic databases Ovid MEDLINE, EMBASE, Cochrane Central, Web-of-Science, PubMed, and Google Scholar were systematically searched to identify eligible studies. Reference lists of the included studies and contact with experts were also used for identification of studies., Selection Criteria: Observational studies that assessed fetal sex and the presence of maternal pregnancy complications within singleton pregnancies., Data Collection and Analyses: Data were extracted by 2 independent reviewers using a predesigned data collection form., Main Results: From 6522 original references, 74 studies were selected, including over 12,5 million women. Male fetal sex was associated with term pre-eclampsia (pooled OR 1.07 [95%CI 1.06 to 1.09]) and gestational diabetes (pooled OR 1.04 [1.02 to 1.07]). All other pregnancy complications (i.e., gestational hypertension, total pre-eclampsia, eclampsia, placental abruption, and post-partum hemorrhage) tended to be associated with male fetal sex, except for preterm pre-eclampsia, which was more associated with female fetal sex. Overall quality of the included studies was good. Between-study heterogeneity was high due to differences in study population and outcome definition., Conclusion: This meta-analysis suggests that the occurrence of pregnancy complications differ according to fetal sex with a higher cardiovascular and metabolic load for the mother in the presence of a male fetus., Funding: None.

Sex is a major determinant of cardiometabolic risk. DNA methylation (DNAm), an important epigenetic mechanism that differs between sexes, has been associated with cardiometabolic diseases. Therefore, we aimed to systematically review studies in adults investigating sex-specific associations of DNAm with intermediate cardiometabolic traits and incident cardiovascular disease including stroke, myocardial infarction (MI) and coronary heart disease (CHD). Five bibliographic databases were searched from inception to 15 July 2019. We selected 35 articles (based on 30 unique studies) from 17,023 references identified, with a total of 14,020 participants of European, North American or Asian ancestry. Four studies reported sex differences between global DNAm and blood lipid levels and stroke risk. In 25 studies that took a genome wide or candidate gene approach, DNAm at 31 gene sites was associated with sex differences in cardiometabolic diseases. The identified genes were PLA2G7, BCL11A, KDM6A, LIPC, ABCG1, PLTP, CETP, ADD1, CNN1B, HOOK2, GFBP-7,PTPN1, GCK, PTX3, ABCG1, GALNT2, CDKN2B, APOE, CTH, GNASAS, INS, PON1, TCN2, CBS, AMT, KDMA6A, FTO, MAP3K13, CCDC8, MMP-2 and ER-α. Prioritized pathway connectivity analysis associated these genes with biological pathways such as vitamin B12 metabolism, statin pathway, plasma lipoprotein, plasma lipoprotein assembly, remodeling and clearance and cholesterol metabolism. Our findings suggest that DNAm might be a promising molecular strategy for understanding sex differences in the pathophysiology of cardiometabolic diseases and that future studies should investigate the effects of sex on epigenetic mechanisms in cardiometabolic risk. In addition, we emphasize the gap between the translational potential and the clinical utilization of cardiometabolic epigenetics., (Copyright © 2020. Published by Elsevier B.V.)

Objective: Long term survival after endovascular aortic aneurysm repair (EVAR) in octogenarians remains unclear. This was evaluated by comparing octogenarians after EVAR with a matched group of octogenarians without an abdominal aortic aneurysm (AAA) from the Rotterdam Study (RS). The influence of complications after EVAR on survival was also studied with the aim of identifying risk factors for the development of complications in octogenarians., Methods: Using propensity score matching (PSM), 83 EVAR octogenarians were matched for comorbidities with 83 octogenarians from the RS, and survival was compared between these two groups using Cox proportional hazard analysis. Then, complications were studied, defined as cardiac or pulmonary, renal deterioration, access site bleeding, acute limb ischaemia or bowel ischaemia, within 30 days of surgery between 83 EVAR octogenarians and 475 EVAR non-octogenarians. Also, the difference in baseline characteristics between the octogenarians with and without complications after EVAR were studied, and survival was compared between the RS controls and the complicated and uncomplicated EVAR octogenarians separately., Results: The total EVAR octogenarian population did not show an increased mortality risk compared with RS octogenarian controls (hazard ratio [HR] 1.28, 95% confidence interval [CI] 0.84-1.97). Post-operative complications occurred in 22 octogenarians (27%) and 59 non-octogenarians (12.4%, p < .001), mainly cardiac, pulmonary, and bleeding complications. All baseline characteristics were similar in the complicated EVAR octogenarians compared with the uncomplicated EVAR octogenarians. After uncomplicated EVAR, octogenarians had a similar survival compared with the RS controls (HR 1.09, 95% CI 0.68-1.77), but after complicated EVAR their mortality risk increased significantly (HR 1.93, 95% CI 1.06-3.54)., Conclusion: After standard EVAR, the life expectancy of octogenarians is the same as that of a matched group from the general population without an AAA, provided they do not develop early post-operative complications. Patient selection and meticulous peri-operative care are key., (Copyright © 2020 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

To date, non-pharmacological interventions (NPI) have been the mainstay for controlling the coronavirus disease-2019 (COVID-19) pandemic. While NPIs are effective in preventing health systems overload, these long-term measures are likely to have significant adverse economic consequences. Therefore, many countries are currently considering to lift the NPIs-increasing the likelihood of disease resurgence. In this regard, dynamic NPIs, with intervals of relaxed social distancing, may provide a more suitable alternative. However, the ideal frequency and duration of intermittent NPIs, and the ideal "break" when interventions can be temporarily relaxed, remain uncertain, especially in resource-poor settings. We employed a multivariate prediction model, based on up-to-date transmission and clinical parameters, to simulate outbreak trajectories in 16 countries, from diverse regions and economic categories. In each country, we then modelled the impacts on intensive care unit (ICU) admissions and deaths over an 18-month period for following scenarios: (1) no intervention, (2) consecutive cycles of mitigation measures followed by a relaxation period, and (3) consecutive cycles of suppression measures followed by a relaxation period. We defined these dynamic interventions based on reduction of the mean reproduction number during each cycle, assuming a basic reproduction number (R 0 ) of 2.2 for no intervention, and subsequent effective reproduction numbers (R) of 0.8 and 0.5 for illustrative dynamic mitigation and suppression interventions, respectively. We found that dynamic cycles of 50-day mitigation followed by a 30-day relaxation reduced transmission, however, were unsuccessful in lowering ICU hospitalizations below manageable limits. By contrast, dynamic cycles of 50-day suppression followed by a 30-day relaxation kept the ICU demands below the national capacities. Additionally, we estimated that a significant number of new infections and deaths, especially in resource-poor countries, would be averted if these dynamic suppression measures were kept in place over an 18-month period. This multi-country analysis demonstrates that intermittent reductions of R below 1 through a potential combination of suppression interventions and relaxation can be an effective strategy for COVID-19 pandemic control. Such a "schedule" of social distancing might be particularly relevant to low-income countries, where a single, prolonged suppression intervention is unsustainable. Efficient implementation of dynamic suppression interventions, therefore, confers a pragmatic option to: (1) prevent critical care overload and deaths, (2) gain time to develop preventive and clinical measures, and (3) reduce economic hardship globally.

Objective: To investigate the role of epigenetics in statins' diabetogenic effect comparing DNA methylation (DNAm) between statin users and nonusers in an epigenome-wide association study in blood., Research Design and Methods: Five cohort studies' participants ( n = 8,270) were classified as statin users when they were on statin therapy at the time of DNAm assessment with Illumina 450K or EPIC array or noncurrent users otherwise. Associations of DNAm with various outcomes like incident type 2 diabetes, plasma glucose, insulin, and insulin resistance (HOMA of insulin resistance [HOMA-IR]) as well as with gene expression were investigated., Results: Discovery ( n = 6,820) and replication ( n = 1,450) phases associated five DNAm sites with statin use: cg17901584 (1.12 × 10 -25 [ DHCR24 ]), cg10177197 (3.94 × 10 -08 [ DHCR24 ]), cg06500161 (2.67 × 10 -23 [ ABCG1 ]), cg27243685 (6.01 × 10 -09 [ ABCG1 ]), and cg05119988 (7.26 × 10 -12 [ SC4MOL ]). Two sites were associated with at least one glycemic trait or type 2 diabetes. Higher cg06500161 methylation was associated with higher fasting glucose, insulin, HOMA-IR, and type 2 diabetes (odds ratio 1.34 [95% CI 1.22, 1.47]). Mediation analyses suggested that ABCG1 methylation partially mediates the effect of statins on high insulin and HOMA-IR. Gene expression analyses showed that statin exposure and ABCG1 methylation were associated with ABCG1 downregulation, suggesting epigenetic regulation of ABCG1 expression. Further, outcomes insulin and HOMA-IR were significantly associated with ABCG1 expression., Conclusions: This study sheds light on potential mechanisms linking statins with type 2 diabetes risk, providing evidence on DNAm partially mediating statins' effects on insulin traits. Further efforts shall disentangle the molecular mechanisms through which statins may induce DNAm changes, potentially leading to ABCG1 epigenetic regulation., (© 2020 by the American Diabetes Association.)