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1. South Asian medical cohorts reveal strong founder effects and high rates of homozygosity

Author: Jeffrey D. Wall, J. Fah Sathirapongsasuti, Ravi Gupta, Asif Rasheed, Radha Venkatesan, Saurabh Belsare, Ramesh Menon, Sameer Phalke, Anuradha Mittal, John Fang, Deepak Tanneeru, Manjari Deshmukh, Akshi Bassi, Jacqueline Robinson, Ruchi Chaudhary, Sakthivel Murugan, Zameer ul-Asar, Imran Saleem, Unzila Ishtiaq, Areej Fatima, Saqib Shafi Sheikh, Shahid Hameed, Mohammad Ishaq, Syed Zahed Rasheed, Fazal-ur-Rehman Memon, Anjum Jalal, Shahid Abbas, Philippe Frossard, Christian Fuchsberger, Lukas Forer, Sebastian Schoenherr, Qixin Bei, Tushar Bhangale, Jennifer Tom, Santosh Gopi Krishna Gadde, Priya B V, Naveen Kumar Naik, Minxian Wang, Pui-Yan Kwok, Amit V. Khera, B. R. Lakshmi, Adam S. Butterworth, Rajiv Chowdhury, John Danesh, Emanuele di Angelantonio, Aliya Naheed, Vinay Goyal, Rukmini M. Kandadai, Hrishikesh Kumar, Rupam Borgohain, Adreesh Mukherjee, Pettarusp M. Wadia, Ravi Yadav, Soaham Desai, Niraj Kumar, Atanu Biswas, Pramod Kumar Pal, Uday B. Muthane, Shymal K. Das, Vedam L. Ramprasad, Prashanth L. Kukkle, Somasekar Seshagiri, Sekar Kathiresan, Arkasubhra Ghosh, V. Mohan, Danish Saleheen, Eric W. Stawiski, and Andrew S. Peterson
Subjects: Science
Abstract: Abstract The benefits of large-scale genetic studies for healthcare of the populations studied are well documented, but these genetic studies have traditionally ignored people from some parts of the world, such as South Asia. Here we describe whole genome sequence (WGS) data from 4806 individuals recruited from the healthcare delivery systems of Pakistan, India and Bangladesh, combined with WGS from 927 individuals from isolated South Asian populations. We characterize population structure in South Asia and describe a genotyping array (SARGAM) and imputation reference panel that are optimized for South Asian genomes. We find evidence for high rates of reproductive isolation, endogamy and consanguinity that vary across the subcontinent and that lead to levels of rare homozygotes that reach 100 times that seen in outbred populations. Founder effects increase the power to associate functional variants with disease processes and make South Asia a uniquely powerful place for population-scale genetic studies.
Published: 2023
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2. Effectiveness, barriers, and facilitators of overweight and obesity prevention strategies in Latin America; a scoping review and qualitative study in ColombiaResearch in context

Author: Gabriela V. Proaño, Lina Marcela Rodriguez Moreno, Maria Jacquelinne Arciniegas, Niliarys Sifre-Acosta, Carlos Espinal, Rajiv Chowdhury, Luis Jorge Hernández Flórez, and Cristina Palacios
Subjects: Colombia, Overweight, Obesity, Prevention, Strategies, Effectiveness, Public aspects of medicine, RA1-1270
Abstract: Summary: Background: This project aimed to synthesize the quantitative/qualitative evidence on the effectiveness of overweight/obesity prevention strategies implemented in Colombia and their barriers and facilitators. Methods: A scoping review was conducted by searching PubMed, SciELO, Scopus, and the grey literature (2012–2023). In-depth interviews were also conducted among key stakeholders on their perception of these strategies’ effectiveness, barriers, and facilitators. Findings: 26 records were included; four studies found positive changes in weight/body mass index, five found positive changes in physical activity, two found positive changes in food intake, and four found positive changes in healthy lifestyle knowledge, perception, attitudes, and habits. The main barrier reported was the obesogenic environment, and the facilitators were program flexibility and community engagement. Eighteen interviews were conducted (one interview per strategy); the main barriers reported were political, lack of evaluation access, economic situation, and lack of articulation; the main facilitators were incorporating the strategy into policies, articulation with stakeholders, and strong oversight. Interpretation: Moderate evidence indicates that these strategies positively impact outcomes related to overweight/obesity in Colombia, but more long-term studies are needed for overweight/obesity reduction. Lack of (1) evaluation and resources (barriers), (2) incorporation into policies (facilitators), and (3) strong stakeholder coordination (facilitators) was identified. Funding: Global Health Consortium, Department of Global Health, FIU.
Published: 2024
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3. Risk Factors of Secondary Cardiovascular Events in a Multi-Ethnic Asian Population with Acute Myocardial Infarction: A Retrospective Cohort Study from Malaysia

Author: Sophia Rasheeqa Ismail, Mohd Shawal Faizal Mohammad, Adam S. Butterworth, Rajiv Chowdhury, John Danesh, Emanuele Di Angelantonio, Simon J. Griffin, Lisa Pennells, Angela M. Wood, Mohd Fairulnizal Md Noh, and Shamsul Azhar Shah
Subjects: myocardial infarction, risk factors, major adverse cardiovascular events, cardiovascular mortality, Asian, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: This retrospective cohort study investigated the incidence and risk factors of major adverse cardiovascular events (MACE) after 1 year of first-documented myocardial infarctions (MIs) in a multi-ethnic Asian population. Secondary MACE were observed in 231 (14.3%) individuals, including 92 (5.7%) cardiovascular-related deaths. Both histories of hypertension and diabetes were associated with secondary MACE after adjustment for age, sex, and ethnicity (HR 1.60 [95%CI 1.22–2.12] and 1.46 [95%CI 1.09–1.97], respectively). With further adjustments for traditional risk factors, individuals with conduction disturbances demonstrated higher risks of MACE: new left-bundle branch block (HR 2.86 [95%CI 1.15–6.55]), right-bundle branch block (HR 2.09 [95%CI 1.02–4.29]), and second-degree heart block (HR 2.45 [95%CI 0.59–10.16]). These associations were broadly similar across different age, sex, and ethnicity groups, although somewhat greater for history of hypertension and BMI among women versus men, for HbA1c control in individuals aged >50 years, and for LVEF ≤ 40% in those with Indian versus Chinese or Bumiputera ethnicities. Several traditional and cardiac risk factors are associated with a higher risk of secondary major adverse cardiovascular events. In addition to hypertension and diabetes, the identification of conduction disturbances in individuals with first-onset MI may be useful for the risk stratification of high-risk individuals.
Published: 2023
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4. A novel index-based decision support toolkit for safe reopening following a generalized lockdown in low and middle-income countries

Author: Abu S. Shonchoy, Khandker S. Ishtiaq, Sajedul Talukder, Nasar U. Ahmed, and Rajiv Chowdhury
Subjects: Medicine, Science
Abstract: Abstract While the effectiveness of lockdowns to reduce Coronavirus Disease-2019 (COVID-19) transmission is well established, uncertainties remain on the lifting principles of these restrictive interventions. World Health Organization recommends case positive rate of 5% or lower as a threshold for safe reopening. However, inadequate testing capacity limits the applicability of this recommendation, especially in the low-income and middle-income countries (LMICs). To develop a practical reopening strategy for LMICs, in this study, we first identify the optimal timing of safe reopening by exploring accessible epidemiological data of 24 countries during the initial COVID-19 surge. We find that a safe opening can occur two weeks after the crossover of daily infection and recovery rates while maintaining a negative trend in daily new cases. Epidemiologic SIRM model-based example simulation supports our findings. Finally, we develop an easily interpretable large-scale reopening (LSR) index, which is an evidence-based toolkit—to guide/inform reopening decision for LMICs.
Published: 2021
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5. Investigating Genetic and Other Determinants of First-Onset Myocardial Infarction in Malaysia: Protocol for the Malaysian Acute Vascular Events Risk Study

Author: Rajiv Chowdhury, Mohd Fairulnizal Md Noh, Sophia Rasheeqa Ismail, Kim Robin van Daalen, Puteri Sofia Nadira Megat Kamaruddin, Siti Hafizah Zulkiply, Nur Hayati Azizul, Norhayati Mustafa Khalid, Azizan Ali, Izyan Mohd Idris, Yong Shih Mei, Shazana Rifham Abdullah, Norfashihah Faridus, Nur Azirah Md Yusof, Nur Najwa Farahin M Yusoff, Rahman Jamal, Aizai Azan Abdul Rahim, Abdul Kahar Abdul Ghapar, Ammu Kutty Radhakrishnan, Alan Yean Yip Fong, Omar Ismail, Saravanan Krishinan, Chuey Yan Lee, Liew Houng Bang, Eashwary Mageswaren, Kauthaman Mahendran, Nor Hanim Mohd Amin, Gunavathy Muthusamy, Aaron Ong Hean Jin, Ahmad Wazi Ramli, Noel Thomas Ross, Anwar Irawan Ruhani, Mansor Yahya, Yusniza Yusoff, Siti Khairani Zainal Abidin, Laryssa Amado, Thomas Bolton, Sophie Weston, Jason Crawte, Niko Ovenden, Ank Michielsen, Md Mostafa Monower, Wan Rozita Wan Mahiyuddin, Angela Wood, Emanuele Di Angelantonio, Nur Suffia Sulaiman, John Danesh, and Adam S Butterworth
Subjects: Medicine, Computer applications to medicine. Medical informatics, R858-859.7
Abstract: BackgroundAlthough the burden of premature myocardial infarction (MI) is high in Malaysia, direct evidence on the determinants of MI in this multi-ethnic population remains sparse. ObjectiveThe Malaysian Acute Vascular Events Risk (MAVERIK) study is a retrospective case-control study established to investigate the genomic, lipid-related, and other determinants of acute MI in Malaysia. In this paper, we report the study protocol and early results. MethodsBy June 2019, we had enrolled approximately 2500 patients with their first MI and 2500 controls without cardiovascular disease, who were frequency-matched by age, sex, and ethnicity, from 17 hospitals in Malaysia. For each participant, serum and whole blood have been collected and stored. Clinical, demographic, and behavioral information has been obtained using a 200-item questionnaire. ResultsTobacco consumption, a history of diabetes, hypertension, markers of visceral adiposity, indicators of lower socioeconomic status, and a family history of coronary disease were more prevalent in cases than in controls. Adjusted (age and sex) logistic regression models for traditional risk factors indicated that current smoking (odds ratio [OR] 4.11, 95% CI 3.56-4.75; P30 kg/m2; OR 1.19, 95% CI 1.05-1.34; P=.009) were associated with MI in age- and sex-adjusted models. ConclusionsThe MAVERIK study can serve as a useful platform to investigate genetic and other risk factors for MI in an understudied Southeast Asian population. It should help to hasten the discovery of disease-causing pathways and inform regionally appropriate strategies that optimize public health action. International Registered Report Identifier (IRRID)RR1-10.2196/31885
Published: 2022
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6. Dietary Fatty Acids, Macronutrient Substitutions, Food Sources and Incidence of Coronary Heart Disease: Findings From the EPIC‐CVD Case‐Cohort Study Across Nine European Countries

Author: Marinka Steur, Laura Johnson, Stephen J. Sharp, Fumiaki Imamura, Ivonne Sluijs, Timothy J. Key, Angela Wood, Rajiv Chowdhury, Marcela Guevara, Marianne U. Jakobsen, Ingegerd Johansson, Albert Koulman, Kim Overvad, Maria‐José Sánchez, Yvonne T. van der Schouw, Antonia Trichopoulou, Elisabete Weiderpass, Maria Wennberg, Ju‐Sheng Zheng, Heiner Boeing, Jolanda M. A. Boer, Marie‐Christine Boutron‐Ruault, Ulrika Ericson, Alicia K. Heath, Inge Huybrechts, Liher Imaz, Rudolf Kaaks, Vittorio Krogh, Tilman Kühn, Cecilie Kyrø, Giovanna Masala, Olle Melander, Conchi Moreno‐Iribas, Salvatore Panico, José R. Quirós, Miguel Rodríguez‐Barranco, Carlotta Sacerdote, Carmen Santiuste, Guri Skeie, Anne Tjønneland, Rosario Tumino, W. M. Monique Verschuren, Raul Zamora‐Ros, Christina C. Dahm, Aurora Perez‐Cornago, Matthias B. Schulze, Tammy Y. N. Tong, Elio Riboli, Nicholas J. Wareham, John Danesh, Adam S. Butterworth, and Nita G. Forouhi
Subjects: coronary heart disease, dietary guidelines, nutritional epidemiology, primary prevention, saturated fat, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background There is controversy about associations between total dietary fatty acids, their classes (saturated fatty acids [SFAs], monounsaturated fatty acids, and polyunsaturated fatty acids), and risk of coronary heart disease (CHD). Specifically, the relevance of food sources of SFAs to CHD associations is uncertain. Methods and Results We conducted a case‐cohort study involving 10 529 incident CHD cases and a random subcohort of 16 730 adults selected from a cohort of 385 747 participants in 9 countries of the EPIC (European Prospective Investigation into Cancer and Nutrition) study. We estimated multivariable adjusted country‐specific hazard ratios (HRs) and 95% CIs per 5% of energy intake from dietary fatty acids, with and without isocaloric macronutrient substitutions, using Prentice‐weighted Cox regression models and pooled results using random‐effects meta‐analysis. We found no evidence for associations of the consumption of total or fatty acid classes with CHD, regardless of macronutrient substitutions. In analyses considering food sources, CHD incidence was lower per 1% higher energy intake of SFAs from yogurt (HR, 0.93 [95% CI, 0.88–0.99]), cheese (HR, 0.98 [95% CI, 0.96–1.00]), and fish (HR, 0.87 [95% CI, 0.75–1.00]), but higher for SFAs from red meat (HR, 1.07 [95% CI, 1.02–1.12]) and butter (HR, 1.02 [95% CI, 1.00–1.04]). Conclusions This observational study found no strong associations of total fatty acids, SFAs, monounsaturated fatty acids, and polyunsaturated fatty acids, with incident CHD. By contrast, we found associations of SFAs with CHD in opposite directions dependent on the food source. These findings should be further confirmed, but support public health recommendations to consider food sources alongside the macronutrients they contain, and suggest the importance of the overall food matrix.
Published: 2021
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7. Cardiometabolic Health: Key in Reducing Adverse COVID-19 Outcomes

Author: Rajiv Chowdhury, Kim R. van Daalen, and Oscar H. Franco
Subjects: covid-19, cardiometabolic health, public health, Diseases of the circulatory (Cardiovascular) system, RC666-701, Public aspects of medicine, RA1-1270
Abstract: Whilst current public health measures focused on good hygiene practices and limiting person-to-person transmission contribute effectively in managing the COVID-19 pandemic, they will not prevent all individuals from becoming infected. Thus, it is of importance to explore what individuals could do to mitigate adverse outcomes. The value of beneficial health behaviours and a healthy lifestyle to improve immune functioning and lower adverse consequences of COVID-19 are increasingly being emphasized. Here we discuss seven key health behaviours and corresponding recommendations that may assist in reducing unfavourable COVID-19 outcomes.
Published: 2020
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8. Epigenetics and Inflammatory Markers: A Systematic Review of the Current Evidence

Author: Valentina Gonzalez-Jaramillo, Eliana Portilla-Fernandez, Marija Glisic, Trudy Voortman, Mohsen Ghanbari, Wichor Bramer, Rajiv Chowdhury, Tamar Nijsten, Abbas Dehghan, Oscar H. Franco, and Jana Nano
Subjects: Pathology, RB1-214
Abstract: Epigenetic mechanisms have been suggested to play a role in the genetic regulation of pathways related to inflammation. Therefore, we aimed to systematically review studies investigating the association between DNA methylation and histone modifications with circulatory inflammation markers in blood. Five bibliographic databases were screened until 21 November of 2017. We included studies conducted on humans that examined the association between epigenetic marks (DNA methylation and/or histone modifications) and a comprehensive list of inflammatory markers. Of the 3,759 identified references, 24 articles were included, involving, 17,399 individuals. There was suggestive evidence for global hypomethylation but better-quality studies in the future have to confirm this. Epigenome-wide association studies (EWAS) (n=7) reported most of the identified differentially methylated genes to be hypomethylated in inflammatory processes. Candidate genes studies reported 18 differentially methylated genes related to several circulatory inflammation markers. There was no overlap in the methylated sites investigated in candidate gene studies and EWAS, except for TMEM49, which was found to be hypomethylated with higher inflammatory markers in both types of studies. The relation between histone modifications and inflammatory markers was assessed by one study only. This review supports an association between epigenetic marks and inflammation, suggesting hypomethylation of the genome. Important gaps in the quality of studies were reported such as inadequate sample size, lack of adjustment for relevant confounders, and failure to replicate the findings. While most of the studies have been focused on C-reactive protein, further efforts should investigate other inflammatory markers.
Published: 2019
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9. Electrocardiographic abnormalities in Chagas disease in the general population: A systematic review and meta-analysis.

Author: Lyda Z Rojas, Marija Glisic, Laura Pletsch-Borba, Luis E Echeverría, Wichor M Bramer, Arjola Bano, Najada Stringa, Asija Zaciragic, Bledar Kraja, Eralda Asllanaj, Rajiv Chowdhury, Carlos A Morillo, Oscar L Rueda-Ochoa, Oscar H Franco, and Taulant Muka
Subjects: Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract: BACKGROUND:Chagas disease (CD) is a major public health concern in Latin America and a potentially serious emerging threat in non-endemic countries. Although the association between CD and cardiac abnormalities is widely reported, study design diversity, sample size and quality challenge the information, calling for its update and synthesis, which would be very useful and relevant for physicians in non-endemic countries where health care implications of CD are real and neglected. We performed to systematically review and meta-analyze population-based studies that compared prevalence of overall and specific ECG abnormalities between CD and non-CD participants in the general population. METHODS:Six databases (EMBASE, Ovid Medline, Web of Science, Cochrane Central, Google Scholar and Lilacs) were searched systematically. Observational studies were included. Odds ratios (OR) were computed using random-effects model. RESULTS:Forty-nine studies were selected, including 34,023(12,276 CD and 21,747 non-CD). Prevalence of overall ECG abnormalities was higher in participants with CD (40.1%; 95%CIs=39.2-41.0) compared to non-CD (24.1%; 95%CIs=23.5-24.7) (OR=2.78; 95%CIs=2.37-3.26). Among specific ECG abnormalities, prevalence of complete right bundle branch block (RBBB) (OR=4.60; 95%CIs=2.97-7.11), left anterior fascicular block (LAFB) (OR=1.60; 95%CIs=1.21-2.13), combination of complete RBBB/LAFB (OR=3.34; 95%CIs=1.76-6.35), first-degree atrioventricular block (A-V B) (OR=1.71; 95%CIs=1.25-2.33), atrial fibrillation (AF) or flutter (OR=2.11; 95%CIs=1.40-3.19) and ventricular extrasystoles (VE) (OR=1.62; 95%CIs=1.14-2.30) was higher in CD compared to non-CD participants. CONCLUSIONS:This systematic review and meta-analysis provides an update and synthesis in this field. This research of observational studies indicates a significant excess in prevalence of ECG abnormalities (40.1%) related to T. cruzi infection in the general population from Chagas endemic regions, being the most common ventricular (RBBB and LAFB), and A-V B (first-degree) node conduction abnormalities as well as arrhythmias (AF or flutter and VE). Also, prevalence of ECG alterations in children was similar to that in adults and suggests earlier onset of cardiac disease.
Published: 2018
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10. The Role of DNA Methylation and Histone Modifications in Neurodegenerative Diseases: A Systematic Review.

Author: Ke-Xin Wen, Jelena Miliç, Bassem El-Khodor, Klodian Dhana, Jana Nano, Tammy Pulido, Bledar Kraja, Asija Zaciragic, Wichor M Bramer, John Troup, Rajiv Chowdhury, M Arfam Ikram, Abbas Dehghan, Taulant Muka, and Oscar H Franco
Subjects: Medicine, Science
Abstract: IMPORTANCE:Epigenetic modifications of the genome, such as DNA methylation and histone modifications, have been reported to play a role in neurodegenerative diseases (ND) such as Alzheimer's disease (AD) and Parkinson's disease (PD). OBJECTIVE:To systematically review studies investigating epigenetic marks in AD or PD. METHODS:Eleven bibliographic databases (Embase.com, Medline (Ovid), Web-of-Science, Scopus, PubMed, Cinahl (EBSCOhost), Cochrane Central, ProQuest, Lilacs, Scielo and Google Scholar) were searched until July 11th 2016 to identify relevant articles. We included all randomized controlled trials, cohort, case-control and cross-sectional studies in humans that examined associations between epigenetic marks and ND. Two independent reviewers, with a third reviewer available for disagreements, performed the abstract and full text selection. Data was extracted using a pre-designed data collection form. RESULTS:Of 6,927 searched references, 73 unique case-control studies met our inclusion criteria. Overall, 11,453 individuals were included in this systematic review (2,640 AD and 2,368 PD outcomes). There was no consistent association between global DNA methylation pattern and any ND. Studies reported epigenetic regulation of 31 genes (including cell communication, apoptosis, and neurogenesis genes in blood and brain tissue) in relation to AD and PD. Methylation at the BDNF, SORBS3 and APP genes in AD were the most consistently reported associations. Methylation of α-synuclein gene (SNCA) was also found to be associated with PD. Seven studies reported histone protein alterations in AD and PD. CONCLUSION:Many studies have investigated epigenetics and ND. Further research should include larger cohort or longitudinal studies, in order to identify clinically significant epigenetic changes. Identifying relevant epigenetic changes could lead to interventional strategies in ND.
Published: 2016
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11. Association of Vasomotor and Other Menopausal Symptoms with Risk of Cardiovascular Disease: A Systematic Review and Meta-Analysis.

Author: Taulant Muka, Clare Oliver-Williams, Veronica Colpani, Setor Kunutsor, Susmita Chowdhury, Rajiv Chowdhury, Maryam Kavousi, and Oscar H Franco
Subjects: Medicine, Science
Abstract: Vasomotor symptoms (hot flushes and night sweats) and other symptoms, including depression, anxiety and panic attacks, are commonly experienced by menopausal women and have been associated with an unfavourable cardiovascular risk profile.To investigate whether presence of menopausal symptoms is associated with the development of cardiovascular disease (CVD).Five electronic databases (Medline, EMBASE and Web of Science) were search until February 17th, 2015 to identify relevant studies. Observational cohort studies or randomised intervention studies were eligible for inclusion if they followed participants prospectively (at least 1 year of follow-up), and reported relevant estimates on the association of any vasomotor symptoms, or other menopausal symptoms, with risk of CVD, coronary heart disease (CHD), or stroke in perimenopausal, menopausal, or postmenopausal women. Data were extracted by two independent reviewers using a pre-designed data collection form. Separate pooled relative risks (RRs) for age and non-established cardiovascular risk factors (e.g., education, ethnicity) adjusted data and for established cardiovascular risk factors and potential mediators-adjusted data (e.g., smoking, body mass index, and hypertension) were calculated.Out of 9,987 initially identified references, ten studies were selected, including 213,976 women with a total of 10,037 cardiovascular disease outcomes. The age and non-established cardiovascular risk factors adjusted RRs) [95% confidence intervals] for development of CHD, Stroke and CVD comparing women with and without any menopausal symptoms were 1.34 [1.13-1.58], 1.30 [0.99-1.70], 1.48 [1.21-1.80] respectively, and the corresponding RRs adjusted for cardiovascular risk factors and potential mediators were 1.18 [1.03-1.35], 1.08 [0.89-1.32], 1.29 [0.98-1.71]. However, these analyses were limited by potential unmeasured confounding and the small number of studies on this topic.Presence of vasomotor symptoms and other menopausal symptoms are generally associated with an increased risk of cardiovascular disease, which is mainly explained by cardiovascular risk factors.
Published: 2016
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12. The role of Decision Support System (DSS) in prevention of cardiovascular disease: a systematic review and meta-analysis.

Author: Raghupathy Anchala, Maria P Pinto, Amir Shroufi, Rajiv Chowdhury, Jean Sanderson, Laura Johnson, Patricia Blanco, Dorairaj Prabhakaran, and Oscar H Franco
Subjects: Medicine, Science
Abstract: BACKGROUND:The potential role of DSS in CVD prevention remains unclear as only a few studies report on patient outcomes for cardiovascular disease. METHODS AND RESULTS:A systematic review and meta-analysis of randomised controlled trials and observational studies was done using Medline, Embase, Cochrane Library, PubMed, Amed, CINAHL, Web of Science, Scopus databases; reference lists of relevant studies to 30 July 2011; and email contact with experts. The primary outcome was prevention of cardiovascular disorders (myocardial infarction, stroke, coronary heart disease, peripheral vascular disorders and heart failure) and management of hypertension owing to decision support systems, clinical decision supports systems, computerized decision support systems, clinical decision making tools and medical decision making (interventions). From 4116 references ten studies met our inclusion criteria (including 16,312 participants). Five papers reported outcomes on blood pressure management, one paper on heart failure, two papers each on stroke, and coronary heart disease. The pooled estimate for CDSS versus control group differences in SBP (mm of Hg) was - 0.99 (95% CI -3.02 to 1.04 mm of Hg; I(2) = 0; p = 0.851). CONCLUSIONS:DSS show an insignificant benefit in the management and control of hypertension (insignificant reduction of SBP). The paucity of well-designed studies on patient related outcomes is a major hindrance that restricts interpretation for evaluating the role of DSS in secondary prevention. Future studies on DSS should (1) evaluate both physician performance and patient outcome measures (2) integrate into the routine clinical workflow with a provision for decision support at the point of care.
Published: 2012
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13. Aging and the COVID-19 pandemic: The inter-related roles of biology, physical wellbeing, social norms and global health systems

Author: Cristina, Baena, Taufique, Joarder, Nasar U, Ahmed, and Rajiv, Chowdhury
Subjects: Aging, Social Norms, Humans, COVID-19, Obstetrics and Gynecology, Global Health, Pandemics, Biology, General Biochemistry, Genetics and Molecular Biology, Aged
Abstract: The coronavirus disease 2019 (COVID-19) pandemic has had a devastating and disproportionate impact on the elderly population. As the virus has swept through the world, already vulnerable elderly populations worldwide have faced a far greater burden of deaths and severe disease, crippling isolation, widespread societal stigma, and wide-ranging practical difficulties in maintaining access to basic health care and social services - all of which have had significant detrimental effects on their mental and physical wellbeing. In this paper, we present an overview of aging and COVID-19 from the interrelated perspectives of underlying biological mechanisms, physical manifestations, societal aspects, and health services related to the excess risk observed among the elderly population. We conclude that to tackle future pandemics in an efficient manner, it is essential to reform national health systems and response strategies from an age perspective. As the global population continues to age, elderly-focused health services should be integrated into the global health systems and global strategies, especially in low- and middle-income countries with historically underfunded public health infrastructure and insufficient gerontological care.
Published: 2023
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14. Risk Factors of Secondary Cardiovascular Events in a Multi-Ethnic Asian Population with Acute Myocardial Infarction: A Retrospective Cohort Study from Malaysia

Author: Shah, Sophia Rasheeqa Ismail, Mohd Shawal Faizal Mohammad, Adam S. Butterworth, Rajiv Chowdhury, John Danesh, Emanuele Di Angelantonio, Simon J. Griffin, Lisa Pennells, Angela M. Wood, Mohd Fairulnizal Md Noh, and Shamsul Azhar
Subjects: myocardial infarction, risk factors, major adverse cardiovascular events, cardiovascular mortality, Asian
Abstract: This retrospective cohort study investigated the incidence and risk factors of major adverse cardiovascular events (MACE) after 1 year of first-documented myocardial infarctions (MIs) in a multi-ethnic Asian population. Secondary MACE were observed in 231 (14.3%) individuals, including 92 (5.7%) cardiovascular-related deaths. Both histories of hypertension and diabetes were associated with secondary MACE after adjustment for age, sex, and ethnicity (HR 1.60 [95%CI 1.22–2.12] and 1.46 [95%CI 1.09–1.97], respectively). With further adjustments for traditional risk factors, individuals with conduction disturbances demonstrated higher risks of MACE: new left-bundle branch block (HR 2.86 [95%CI 1.15–6.55]), right-bundle branch block (HR 2.09 [95%CI 1.02–4.29]), and second-degree heart block (HR 2.45 [95%CI 0.59–10.16]). These associations were broadly similar across different age, sex, and ethnicity groups, although somewhat greater for history of hypertension and BMI among women versus men, for HbA1c control in individuals aged >50 years, and for LVEF ≤ 40% in those with Indian versus Chinese or Bumiputera ethnicities. Several traditional and cardiac risk factors are associated with a higher risk of secondary major adverse cardiovascular events. In addition to hypertension and diabetes, the identification of conduction disturbances in individuals with first-onset MI may be useful for the risk stratification of high-risk individuals.
Published: 2023
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15. Gene Sequencing Identifies Perturbation in Nitric Oxide Signaling as a Nonlipid Molecular Subtype of Coronary Artery Disease

Author: Amit V. Khera, Minxian Wang, Mark Chaffin, Connor A. Emdin, Nilesh J. Samani, Heribert Schunkert, Hugh Watkins, Ruth McPherson, Jeanette Erdmann, Roberto Elosua, Eric Boerwinkle, Diego Ardissino, Adam S. Butterworth, Emanuele Di Angelantonio, Aliya Naheed, John Danesh, Rajiv Chowdhury, Harlan M. Krumholz, Wayne H.-H. Sheu, Stephen S. Rich, Jerome I. Rotter, Yii-der Ida Chen, Stacey Gabriel, Eric S. Lander, Danish Saleheen, and Sekar Kathiresan
Subjects: General Medicine
Abstract: Background: A key goal of precision medicine is to disaggregate common, complex diseases into discrete molecular subtypes. Rare coding variants in the low-density lipoprotein receptor gene ( LDLR ) are identified in 1% to 2% of coronary artery disease (CAD) patients, defining a molecular subtype with risk driven by hypercholesterolemia. Methods: To search for additional subtypes, we compared the frequency of rare, predicted loss-of-function and damaging missense variants aggregated within a given gene in 41 081 CAD cases versus 217 115 controls. Results: Rare variants in LDLR were most strongly associated with CAD, present in 1% of cases and associated with 4.4-fold increased CAD risk. A second subtype was characterized by variants in endothelial nitric oxide synthase gene ( NOS3 ), a key enzyme regulating vascular tone, endothelial function, and platelet aggregation. A rare predicted loss-of-function or damaging missense variants in NOS3 was present in 0.6% of cases and associated with 2.42-fold increased risk of CAD (95% CI, 1.80–3.26; P =5.50×10 −9 ). These variants were associated with higher systolic blood pressure (+3.25 mm Hg; [95% CI, 1.86–4.65]; P =5.00×10 −6 ) and increased risk of hypertension (adjusted odds ratio 1.31; [95% CI, 1.14–1.51]; P =2.00×10 −4 ) but not circulating cholesterol concentrations, suggesting that, beyond lipid pathways, nitric oxide synthesis is a key nonlipid driver of CAD risk. Conclusions: Beyond LDLR , we identified an additional nonlipid molecular subtype of CAD characterized by rare variants in the NOS3 gene.
Published: 2022

16. Validation of a Genome-Wide Polygenic Score for Coronary Artery Disease in South Asians

Author: Minxian Wang, Aliya Naheed, Muralidhar Kanchi, Manjari Deshmukh, Aniketh Vijay Balegadde, Adam S. Butterworth, Sanika Apte, Praveena Lakshmipathy, Oshin Mathew, Ravi Gupta, Alben Sigamani, Emanuele Di Angelantonio, Rajiv Chowdhury, Ajit S. Mullasari, Ramesh Menon, Rajeev Gupta, Karthikeyan Rajendran, Rajesh Thachathodiyl, Michael Inouye, Amit Khera, Sakthivel Murugan, Mark Chaffin, Aniruddh P. Patel, Hisham Ahamed, Sumathi Sundaram, Krishnan Swaminathan, John Danesh, Sekar Kathiresan, Andrew S. Peterson, Krishna Kumar Sharma, Christina S. Devanboo, Ramprasad Vedam, Sanghamitra Mishra, Deepak Tanneeru, Sam Santhosh, Thomas Alexander, Butterworth, Adam [0000-0002-6915-9015], Danesh, John [0000-0003-1158-6791], Di Angelantonio, Emanuele [0000-0001-8776-6719], Inouye, Michael [0000-0001-9413-6520], and Apollo - University of Cambridge Repository
Subjects: Adult, Male, Multifactorial Inheritance, medicine.medical_specialty, South asia, India, Coronary Artery Disease, 030204 cardiovascular system & hematology, Dna variants, Genome, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, South Asian, Humans, Medicine, Genomic medicine, polygenic score, 030212 general & internal medicine, Aged, Bangladesh, business.industry, Middle Aged, medicine.disease, genomic medicine, Case-Control Studies, Female, Cardiology and Cardiovascular Medicine, business, Genome-Wide Association Study
Abstract: BACKGROUND: Genome-wide polygenic scores (GPS) integrate information from many common DNA variants into a single number. Because rates of coronary artery disease (CAD) are substantially higher among South Asians, a GPS to identify high-risk individuals may be particularly useful in this population. OBJECTIVES: This analysis used summary statistics from a prior genome-wide association study to derive a new GPSCAD for South Asians. METHODS: This GPSCAD was validated in 7,244 South Asian UK Biobank participants and tested in 491 individuals from a case-control study in Bangladesh. Next, a static ancestry and GPSCAD reference distribution was built using whole-genome sequencing from 1,522 Indian individuals, and a framework was tested for projecting individuals onto this static ancestry and GPSCAD reference distribution using 1,800 CAD cases and 1,163 control subjects newly recruited in India. RESULTS: The GPSCAD, containing 6,630,150 common DNA variants, had an odds ratio (OR) per SD of 1.58 in South Asian UK Biobank participants and 1.60 in the Bangladeshi study (p
Published: 2020
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17. Investigating Genetic and Other Determinants of First-Onset Myocardial Infarction in Malaysia: Protocol for the Malaysian Acute Vascular Events Risk Study

Author: Izyan Mohd Idris, Sophia Rasheeqa Ismail, Eashwary Mageswaren, Niko Ovenden, Rajiv Chowdhury, Thomas A. W. Bolton, Rahman Jamal, Siti Hafizah Zulkiply, Ammu Kutty Radhakrishnan, Jason Crawte, Puteri Sofia Nadira Megat Kamaruddin, Nur Suffia Sulaiman, Siti Khairani Zainal Abidin, Abdul Kahar Abdul Ghapar, Mohd Fairulnizal Md Noh, Kauthaman A Mahendran, Alan Yean Yip Fong, John Danesh, Ahmad Wazi Ramli, Liew Houng Bang, Anwar Irawan Ruhani, Shazana Rifham Abdullah, Noel Thomas Ross, Aizai Azan Abdul Rahim, Angela M. Wood, Wan Rozita Wan Mahiyuddin, Kim Robin van Daalen, Sophie Weston, Nur Hayati Azizul, Lee Chuey Yan, Laryssa Amado, Yong Shih Mei, Azizan Ali, Mansor Yahya, Omar Ismail, Nor Hanim Mohd Amin, Aaron Ong Hean Jin, Gunavathy Muthusamy, Ank Michielsen, Emanuele Di Angelantonio, Saravanan Krishinan, Norfashihah Faridus, Adam S. Butterworth, Yusniza Yusoff, Mostafa Monower, Nur Azirah Md Yusof, Nur Najwa Farahin M Yusoff, and Norhayati Mustafa Khalid
Subjects: Protocol (science), medicine.medical_specialty, myocardial infarction, Genetic, business.industry, Emergency medicine, medicine, Malaysia, General Medicine, Myocardial infarction, medicine.disease, business, MAVERICK
Abstract: Background Although the burden of premature myocardial infarction (MI) is high in Malaysia, direct evidence on the determinants of MI in this multi-ethnic population remains sparse. Objective The Malaysian Acute Vascular Events Risk (MAVERIK) study is a retrospective case-control study established to investigate the genomic, lipid-related, and other determinants of acute MI in Malaysia. In this paper, we report the study protocol and early results. Methods By June 2019, we had enrolled approximately 2500 patients with their first MI and 2500 controls without cardiovascular disease, who were frequency-matched by age, sex, and ethnicity, from 17 hospitals in Malaysia. For each participant, serum and whole blood have been collected and stored. Clinical, demographic, and behavioral information has been obtained using a 200-item questionnaire. Results Tobacco consumption, a history of diabetes, hypertension, markers of visceral adiposity, indicators of lower socioeconomic status, and a family history of coronary disease were more prevalent in cases than in controls. Adjusted (age and sex) logistic regression models for traditional risk factors indicated that current smoking (odds ratio [OR] 4.11, 95% CI 3.56-4.75; P30 kg/m2; OR 1.19, 95% CI 1.05-1.34; P=.009) were associated with MI in age- and sex-adjusted models. Conclusions The MAVERIK study can serve as a useful platform to investigate genetic and other risk factors for MI in an understudied Southeast Asian population. It should help to hasten the discovery of disease-causing pathways and inform regionally appropriate strategies that optimize public health action. International Registered Report Identifier (IRRID) RR1-10.2196/31885
Published: 2022

18. Rare coding variants in 35 genes associate with circulating lipid levels-A multi-ancestry analysis of 170,000 exomes

Author: George Hindy, Peter Dornbos, Mark D. Chaffin, Dajiang J. Liu, Minxian Wang, Margaret Sunitha Selvaraj, David Zhang, Joseph Park, Carlos A. Aguilar-Salinas, Lucinda Antonacci-Fulton, Diego Ardissino, Donna K. Arnett, Stella Aslibekyan, Gil Atzmon, Christie M. Ballantyne, Francisco Barajas-Olmos, Nir Barzilai, Lewis C. Becker, Lawrence F. Bielak, Joshua C. Bis, John Blangero, Eric Boerwinkle, Lori L. Bonnycastle, Erwin Bottinger, Donald W. Bowden, Matthew J. Bown, Jennifer A. Brody, Jai G. Broome, Noël P. Burtt, Brian E. Cade, Federico Centeno-Cruz, Edmund Chan, Yi-Cheng Chang, Yii-Der I. Chen, Ching-Yu Cheng, Won Jung Choi, Rajiv Chowdhury, Cecilia Contreras-Cubas, Emilio J. Córdova, Adolfo Correa, L. Adrienne Cupples, Joanne E. Curran, John Danesh, Paul S. de Vries, Ralph A. DeFronzo, Harsha Doddapaneni, Ravindranath Duggirala, Susan K. Dutcher, Patrick T. Ellinor, Leslie S. Emery, Jose C. Florez, Myriam Fornage, Barry I. Freedman, Valentin Fuster, Ma. Eugenia Garay-Sevilla, Humberto García-Ortiz, Soren Germer, Richard A. Gibbs, Christian Gieger, Benjamin Glaser, Clicerio Gonzalez, Maria Elena Gonzalez-Villalpando, Mariaelisa Graff, Sarah E. Graham, Niels Grarup, Leif C. Groop, Xiuqing Guo, Namrata Gupta, Sohee Han, Craig L. Hanis, Torben Hansen, Jiang He, Nancy L. Heard-Costa, Yi-Jen Hung, Mi Yeong Hwang, Marguerite R. Irvin, Sergio Islas-Andrade, Gail P. Jarvik, Hyun Min Kang, Sharon L.R. Kardia, Tanika Kelly, Eimear E. Kenny, Alyna T. Khan, Bong-Jo Kim, Ryan W. Kim, Young Jin Kim, Heikki A. Koistinen, Charles Kooperberg, Johanna Kuusisto, Soo Heon Kwak, Markku Laakso, Leslie A. Lange, Jiwon Lee, Juyoung Lee, Seonwook Lee, Donna M. Lehman, Rozenn N. Lemaitre, Allan Linneberg, Jianjun Liu, Ruth J.F. Loos, Steven A. Lubitz, Valeriya Lyssenko, Ronald C.W. Ma, Lisa Warsinger Martin, Angélica Martínez-Hernández, Rasika A. Mathias, Stephen T. McGarvey, Ruth McPherson, James B. Meigs, Thomas Meitinger, Olle Melander, Elvia Mendoza-Caamal, Ginger A. Metcalf, Xuenan Mi, Karen L. Mohlke, May E. Montasser, Jee-Young Moon, Hortensia Moreno-Macías, Alanna C. Morrison, Donna M. Muzny, Sarah C. Nelson, Peter M. Nilsson, Jeffrey R. O’Connell, Marju Orho-Melander, Lorena Orozco, Colin N.A. Palmer, Nicholette D. Palmer, Cheol Joo Park, Kyong Soo Park, Oluf Pedersen, Juan M. Peralta, Patricia A. Peyser, Wendy S. Post, Michael Preuss, Bruce M. Psaty, Qibin Qi, D.C. Rao, Susan Redline, Alexander P. Reiner, Cristina Revilla-Monsalve, Stephen S. Rich, Nilesh Samani, Heribert Schunkert, Claudia Schurmann, Daekwan Seo, Jeong-Sun Seo, Xueling Sim, Rob Sladek, Kerrin S. Small, Wing Yee So, Adrienne M. Stilp, E. Shyong Tai, Claudia H.T. Tam, Kent D. Taylor, Yik Ying Teo, Farook Thameem, Brian Tomlinson, Michael Y. Tsai, Tiinamaija Tuomi, Jaakko Tuomilehto, Teresa Tusié-Luna, Miriam S. Udler, Rob M. van Dam, Ramachandran S. Vasan, Karine A. Viaud Martinez, Fei Fei Wang, Xuzhi Wang, Hugh Watkins, Daniel E. Weeks, James G. Wilson, Daniel R. Witte, Tien-Yin Wong, Lisa R. Yanek, Sekar Kathiresan, Daniel J. Rader, Jerome I. Rotter, Michael Boehnke, Mark I. McCarthy, Cristen J. Willer, Pradeep Natarajan, Jason A. Flannick, Amit V. Khera, Gina M. Peloso, NIH - National Heart, Lung, and Blood Institute (NHLBI) (Estados Unidos), Centre of Excellence in Complex Disease Genetics, HUS Abdominal Center, Institute for Molecular Medicine Finland, Leif Groop Research Group, Clinicum, Department of Medicine, HUS Internal Medicine and Rehabilitation, University of Helsinki, and Department of Public Health
Subjects: APOC3, Blood Glucose, Multifactorial Inheritance, gene-based association, Polymorphism, Single Nucleotide, Article, Open Reading Frames, ANGPTL3, lipid, OF-FUNCTION MUTATIONS, BINDING, Databases, Genetic, SEQUENCE VARIANTS, Genetics, Humans, Exome, Genetic Predisposition to Disease, SINUSOIDAL ENDOTHELIAL-CELLS, Genetics (clinical), Alleles, RISK, IDENTIFICATION, 1184 Genetics, developmental biology, physiology, association, cholesterol, Genetic Variation, Computational Biology, Molecular Sequence Annotation, PERILIPIN, Lipid Metabolism, Lipids, Genetics, Population, Phenotype, Diabetes Mellitus, Type 2, Liver, Case-Control Studies, exome sequencing, TRIGLYCERIDES, Genome-Wide Association Study
Abstract: Large-scale gene sequencing studies for complex traits have the potential to identify causal genes with therapeutic implications. We performed gene-based association testing of blood lipid levels with rare (minor allele frequency < 1%) predicted damaging coding variation by using sequence data from >170,000 individuals from multiple ancestries: 97,493 European, 30,025 South Asian, 16,507 African, 16,440 Hispanic/Latino, 10,420 East Asian, and 1,182 Samoan. We identified 35 genes associated with circulating lipid levels; some of these genes have not been previously associated with lipid levels when using rare coding variation from population-based samples. We prioritize 32 genes in array-based genome-wide association study (GWAS) loci based on aggregations of rare coding variants; three (EVI5, SH2B3, and PLIN1) had no prior association of rare coding variants with lipid levels. Most of our associated genes showed evidence of association among multiple ancestries. Finally, we observed an enrichment of gene-based associations for low-density lipoprotein cholesterol drug target genes and for genes closest to GWAS index single-nucleotide polymorphisms (SNPs). Our results demonstrate that gene-based associations can be beneficial for drug target development and provide evidence that the gene closest to the array-based GWAS index SNP is often the functional gene for blood lipid levels. This work was supported by a grant from the Swedish Research Council (2016-06830) and grants from the National Heart, Lung, and Blood Institute (NHLBI): R01HL142711 and R01HL127564. Please refer to the supplemental information for the full acknowledgements. Sí
Published: 2022
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19. Trends in the prevalence of overweight among Bangladeshi children aged 24–59 months (2004–2014) by sex and socioeconomic status

Author: Shajedur Rahman Shawon, Gourab Adhikary, Arif Chowdhury, Blake Thomson, Fariha Binte Hossain, Rajiv Chowdhury, and Nick Townsend
Subjects: Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), 030209 endocrinology & metabolism, Overweight, Logistic regression, Odds, 03 medical and health sciences, 0302 clinical medicine, Prevalence, medicine, Humans, 030212 general & internal medicine, Socioeconomic status, Bangladesh, Nutrition and Dietetics, business.industry, Public health, Confounding, Odds ratio, medicine.disease, Obesity, Cross-Sectional Studies, Social Class, Child, Preschool, Female, medicine.symptom, business, Demography
Abstract: Background While recent evidence suggests that the overall prevalence of overweight in young children in Bangladesh is low, little is known about variation in trends by sex, socioeconomic status, urbanicity, and region. We investigated the trends in overweight among children aged 24-59 months by these factors, using nationally representative samples from Bangladesh Demographic and Health Surveys (BDHS) between 2004 and 2014. Methods Data from four BDHS surveys conducted between 2004 and 2014, with valid height and weight measurements of children, were included in this study (n = 15,648). BMI was calculated and the prevalence of overweight (including obesity) was reported using the International Obesity Taskforce (IOTF) classification system. To explore the association between socioeconomic status and childhood overweight, we used multivariable logistic regression. Results The overall prevalence of overweight among children aged 24-59 months increased from 1.60% (95% CI: 1.20-2.05%) in 2004 to 2.33% (95% CI: 1.82-2.76%) in 2014. Among girls, the overweight trend increased significantly (adjusted odds ratio (OR) comparing 2014 vs. 2004: 2.02 95% CI: 1.52-2.68), whereas among boys the trend remained steady. When compared with households with the poorest wealth index, households with richest wealth index had higher odds of childhood overweight among both boys (OR 2.39, 95% CI: 1.76-3.25) and girls (OR 1.86, 95% CI: 1.35-2.55). Higher household education level was also associated with childhood overweight. Subgroup analyses showed that relative inequalities by these factors increased between 2004 and 2014 when adjusted for potential confounders. Conclusions There is a rising trend in overweight prevalence exclusively among girls aged 24-59 months in Bangladesh. Childhood overweight is associated with higher household education and wealth index, and the relative disparity by these factors appears to be increasing over time. These unmet inequalities should be considered while developing national public health programs and strategies.
Published: 2019
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20. Dietary fatty acids, macronutrient substitutions, food sources and incidence of coronary heart disease: Findings from the EPIC-CVD case-cohort study across nine european countries

Author: Matthias B. Schulze, Vittorio Krogh, Rosario Tumino, Nita G. Forouhi, Christina C. Dahm, Kim Overvad, Marie-Christine Boutron-Ruault, Angela M. Wood, Yvonne T. van der Schouw, Guri Skeie, Laura Johnson, Fumiaki Imamura, Ivonne Sluijs, José R Quirós, Elisabete Weiderpass, Nicholas J. Wareham, Timothy J. Key, Adam S. Butterworth, Giovanna Masala, Alicia K Heath, Albert Koulman, Conchi Moreno-Iribas, Inge Huybrechts, John Danesh, Stephen J. Sharp, Salvatore Panico, Carlotta Sacerdote, Aurora Perez-Cornago, Olle Melander, Rudolf Kaaks, Elio Riboli, Tammy Y.N. Tong, María José Sánchez, Rajiv Chowdhury, Ju-Sheng Zheng, Miguel Rodríguez-Barranco, W M Monique Verschuren, Marinka Steur, Ingegerd Johansson, Heiner Boeing, Anne Tjønneland, Carmen Santiuste, Antonia Trichopoulou, Maria Wennberg, Jolanda M. A. Boer, Marcela Guevara, Cecilie Kyrø, Raul Zamora-Ros, Liher Imaz, Tilman Kühn, Marianne Uhre Jakobsen, Ulrika Ericson, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, G0800270, MR/L003120/1, Pfizer, AstraZeneca, Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC, Merck Sharp and Dohme, MSD, Seventh Framework Programme, FP7: HEALTH-F2-2012-279233, National Research Council, NRC, University of Maryland School of Public Health, SPH, Medical Research Council, MRC: MC_UU_00006/1, National Institute for Health Research, NIHR, British Heart Foundation, BHF: RG/18/13/33946, RG13/13/30194, SP/09/002, Cancer Research UK, CRUK: C8221/A29017, MR/M012190/1, World Cancer Research Fund, WCRF, Imperial College London, European Research Council, ERC: 268834, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, European Social Fund, ESF, Sixth Framework Programme, FP6: LSHM_CT_2006_037197, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Akademi Sains Malaysia, ASM: MR/P013880/1, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, UCLH Biomedical Research Centre, NIHR BRC: BRC-1215-20014, NIHR Imperial Biomedical Research Centre, BRC, Hellenic Health Foundation, HHF: CP15/00100, IS-BRC-1215-20014, MC_UU_00006/3, Dr Danesh reports grants, personal fees and non-financial support from Merck Sharp & Dohme, grants, personal fees, and nonfinancial support from Novartis, grants from Pfizer, and grants from AstraZeneca outside the submitted work. He is member of the International Cardiovascular and Metabolic Advisory Board for Novartis (since 2010), the Steering Committee of UK Biobank (since 2011), the MRC International Advisory Group (ING) member, London (since 2013), the MRC High Throughput Science ‘Omics Panel Member, London (since 2013), the Scientific Advisory Committee for Sanofi (since 2013), the International Cardiovascular and Metabolism Research and Development Portfolio Committee for Novartis, and the Astra Zeneca Genomics Advisory Board (2018). Dr Butterworth reports grants outside of this work from AstraZeneca, Biogen, BioMarin, Bioverativ, Merck, Novartis, Pfizer, and Sanofi and personal fees from Novartis. The remaining authors have no disclosures to report., EPIC-CVD was supported by the European Commission Framework Programme 7 (HEALTH-F2-2012-279233), and the European Research Council (268834). The coordinating center was supported by core funding from the: United Kingdom MRC (G0800270, MR/L003120/1), British Heart Foundation (BHF) (SP/09/002, RG13/13/30194, RG/18/13/33946), and National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC) (BRC-1215-20014).* The establishment of the study subcohort was supported by the European Union Sixth Framework Programme (grant LSHM_CT_2006_037197 to the InterAct project) and the MRC Epidemiology Unit (grant MC_UU_00006/1). The coordination of EPIC is financially supported by International Agency for Research on Cancer and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by NIHR Imperial BRC. The national cohorts are supported by: Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (France), German Cancer Aid, German Cancer Research Center, German Institute of Human Nutrition Potsdam-Rehbruecke, Federal Ministry of Education and Research (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Zorg Onderzoek Nederland, World Cancer Research Fund, Statistics Netherlands (the Netherlands), Health Research Fund– Instituto de Salud Carlos III, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, C8221/A29017 to EPIC-Oxford), MRC (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). EPIC-Greece was supported by the Hellenic Health Foundation (Greece). M.S., N.J.W., N.G.F., and F.I. acknowledge support from MRC Epidemiology Unit (MC_UU_00006/1 and MC_UU_00006/3). N.J.W. and N.G.F. acknowledge support from NIHR* Cambridge BRC: Nutrition, Diet, and Lifestyle Research Theme (IS-BRC-1215-20014) and NGF is a NIHR Senior Investigator Award holder. M.S. was also supported by BHF for part of this work while working in the BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. R.Z.-R. thanks the 'Miguel Servet' program (CP15/00100) from the Institute of Health Carlos III (co-funded by the European Social Fund–European Social Fund Investing in Your Future). A.W. was supported by a BHF-Turing Cardiovascular Data Science Award and by the European Commission-Innovative Medicines Initiative (BigData@Heart). R.C. was funded by a MRC-Newton project grant to study genetic risk factors of cardiovascular disease among Southeast Asian people and the Academy of Sciences Malaysia (grant no. MR/P013880/1) and a United Kingdom Research and Innovation-Global Challenges Research Fund Project Grant to study risk factors of noncommunicable diseases in Bangladesh. J.D. holds a BHF Professorship and a NIHR Senior Investigator Award., Steur, Marinka [0000-0002-9028-0290], Imamura, Fumiaki [0000-0002-6841-8396], Key, Timothy J [0000-0003-2294-307X], Chowdhury, Rajiv [0000-0003-4881-5690], Guevara, Marcela [0000-0001-9242-6364], Jakobsen, Marianne U [0000-0001-6518-4136], Johansson, Ingegerd [0000-0002-9227-8434], Weiderpass, Elisabete [0000-0003-2237-0128], Boer, Jolanda MA [0000-0002-9714-4304], Boutron-Ruault, Marie-Christine [0000-0002-5956-5693], Heath, Alicia K [0000-0001-6517-1300], Huybrechts, Inge [0000-0003-3838-855X], Imaz, Liher [0000-0002-3777-4953], Masala, Giovanna [0000-0002-5758-9069], Zamora-Ros, Raul [0000-0002-6236-6804], Perez-Cornago, Aurora [0000-0002-5652-356X], Tong, Tammy YN [0000-0002-0284-8959], Wareham, Nicholas J [0000-0003-1422-2993], Forouhi, Nita G [0000-0002-5041-248X], and Apollo - University of Cambridge Repository
Subjects: Saturated fat, Physiology, Coronary Disease, 030204 cardiovascular system & hematology, EPIC, Cohort Studies, 0302 clinical medicine, Medicine, Cardiac and Cardiovascular Systems, 030212 general & internal medicine, 1102 Cardiorespiratory Medicine and Haematology, 2. Zero hunger, chemistry.chemical_classification, Nutrition and Dietetics, Kardiologi, Primary prevention, Incidence, Incidence (epidemiology), Fatty Acids, Fatty acids in human nutrition, 3. Good health, Europe, Näringslära, Coronary heart disease, Dietary guidelines, Cardiology and Cardiovascular Medicine, Polyunsaturated fatty acid, Cohort study, Malalties coronàries, 03 medical and health sciences, SDG 3 - Good Health and Well-being, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Àcids grassos en la nutrició, Diseases of the circulatory (Cardiovascular) system, Humans, Nutritional epidemiology, business.industry, Nutrients, Dietary Fats, chemistry, Food, RC666-701, SPS Exercise, Nutrition and Health Sciences, business
Abstract: EPIC-CVD was supported by the European Commission Framework Programme 7 (HEALTH-F2-2012-279233), and the European Research Council (268834). The coordinating center was supported by core funding from the: United Kingdom MRC (G0800270; MR/L003120/1), British Heart Foundation (BHF) (SP/09/002; RG13/13/30194; RG/18/13/33946), and National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC) (BRC-1215-20014).* The establishment of the study subcohort was supported by the European Union Sixth Framework Programme (grant LSHM_CT_ 2006_037197 to the InterAct project) and the MRC Epidemiology Unit (grant MC_UU_00006/1). The coordination of EPIC is financially supported by International Agency for Research on Cancer and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by NIHR Imperial BRC. The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (France); German Cancer Aid, German Cancer Research Center, German Institute of Human Nutrition Potsdam-Rehbruecke, Federal Ministry of Education and Research (Germany); Associazione Italiana per la Ricerca sul Cancro--AIRC--Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Zorg Onderzoek Nederland, World Cancer Research Fund, Statistics Netherlands (the Netherlands); Health Research Fund-Instituto de Salud Carlos III, Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skane and Vasterbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), MRC (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (United Kingdom). EPIC-Greece was supported by the Hellenic Health Foundation (Greece). M.S., N.J.W., N.G.F., and F.I. acknowledge support from MRC Epidemiology Unit (MC_UU_ 00006/1 and MC_UU_00006/3). N.J.W. and N.G.F. acknowledge support from NIHR* Cambridge BRC: Nutrition, Diet, and Lifestyle Research Theme (IS-BRC-1215--20014) and NGF is a NIHR Senior Investigator Award holder. M.S. was also supported by BHF for part of this work while working in the BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. R. Z.-R. thanks the "Miguel Servet" program (CP15/00100) from the Institute of Health Carlos III (co-funded by the European Social Fund--European Social Fund Investing in Your Future). A.W. was supported by a BHF-Turing Cardiovascular Data Science Award and by the European Commission-Innovative Medicines Initiative (BigData@Heart).R.C.was funded by a MRC-Newton project grant to study genetic risk factors of cardiovascular disease among Southeast Asian people and the Academy of Sciences Malaysia (grant no. MR/P013880/1) and a United Kingdom Research and Innovation-Global Challenges Research Fund Project Grant to study risk factors of noncommunicable diseases in Bangladesh. J.D. holds a BHF Professorship and a NIHR Senior Investigator Award. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/World Health Organization. The funders of the study had no role in study design, data collection, analysis, data interpretation, or writing of the article, or in the decision to submit for publication. M.S. had full access to all the data in the study, and M.S. and N.G.F. had final responsibility for the decision to submit for publication., BACKGROUND: There is controversy about associations between total dietary fatty acids, their classes (saturated fatty acids [SFAs], monounsaturated fatty acids, and polyunsaturated fatty acids), and risk of coronary heart disease (CHD). Specifically, the relevance of food sources of SFAs to CHD associations is uncertain. METHODS AND RESULTS: We conducted a case-cohort study involving 10 529 incident CHD cases and a random subcohort of 16 730 adults selected from a cohort of 385 747 participants in 9 countries of the EPIC (European Prospective Investigation into Cancer and Nutrition) study. We estimated multivariable adjusted country-specific hazard ratios (HRs) and 95% CIs per 5% of energy intake from dietary fatty acids, with and without isocaloric macronutrient substitutions, using Prentice-weighted Cox regression models and pooled results using random-effects meta-analysis. We found no evidence for associations of the consumption of total or fatty acid classes with CHD, regardless of macronutrient substitutions. In analyses considering food sources, CHD incidence was lower per 1% higher energy intake of SFAs from yogurt (HR, 0.93 [95% CI, 0.88–0.99]), cheese (HR, 0.98 [95% CI, 0.96–1.00]), and fish (HR, 0.87 [95% CI, 0.75–1.00]), but higher for SFAs from red meat (HR, 1.07 [95% CI, 1.02–1.12]) and butter (HR, 1.02 [95% CI, 1.00–1.04]). CONCLUSIONS: This observational study found no strong associations of total fatty acids, SFAs, monounsaturated fatty acids, and polyunsaturated fatty acids, with incident CHD. By contrast, we found associations of SFAs with CHD in opposite directions dependent on the food source. These findings should be further confirmed, but support public health recommendations to consider food sources alongside the macronutrients they contain, and suggest the importance of the overall food matrix., European Commission Framework Programme 7 HEALTH-F2-2012-279233, European Research Council (ERC), European Commission 268834, UK Research & Innovation (UKRI), Medical Research Council UK (MRC) G0800270 MR/L003120/1, British Heart Foundation SP/09/002 RG13/13/30194 RG/18/13/33946, National Institute for Health Research (NIHR) BRC-1215-20014, European Commission LSHM_CT_ 2006_037197, Medical Research Council UK (MRC) MC_UU_ 00006/1 MC_UU_00006/3, International Agency for Research on Cancer, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Danish Cancer Society, Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (France), German Cancer Aid, German Cancer Research Center, German Institute of Human Nutrition Potsdam, Rehbruecke, Federal Ministry of Education and Research (Germany), Fondazione AIRC per la ricerca sul cancro, Compagnia di San Paolo, Dutch Ministry of Public Health, Welfare and Sports, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Zorg Onderzoek Nederland, World Cancer Research Fund International (WCRF), Netherlands Government, Instituto de Salud Carlos III, Junta de Andalucia, Regional Government of Asturias, Basque Government, Regional Government of Murcia, Regional Government of Navarra, Catalan Institute of Oncology (Spain), Swedish Cancer Society, County Council of Skane (Sweden), County Council of Vasterbotten (Sweden), Cancer Research UK 14136 C8221/A29017, Medical Research Council UK (MRC) 1000143 MR/M012190/1, Hellenic Health Foundation (Greece), NIHR* Cambridge BRC: Nutrition, Diet, and Lifestyle Research Theme IS-BRC-1215-20014, British Heart Foundation, Institute of Health Carlos III (European Social Fund-European Social Fund Investing in Your Future) CP15/00100, BHF-Turing Cardiovascular Data Science Award, European Commission-Innovative Medicines Initiative (BigData@Heart), MRC-Newton project grant MR/P013880/1, United Kingdom Research and Innovation-Global Challenges Research Fund, NIHR Senior Investigator Award
Published: 2021
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21. Investigating Genetic and Other Determinants of First-Onset Myocardial Infarction in Malaysia: Protocol for the Malaysian Acute Vascular Events Risk Study (Preprint)

Author: Rajiv Chowdhury, Mohd Fairulnizal Md Noh, Sophia Rasheeqa Ismail, Kim Robin van Daalen, Puteri Sofia Nadira Megat Kamaruddin, Siti Hafizah Zulkiply, Nur Hayati Azizul, Norhayati Mustafa Khalid, Azizan Ali, Izyan Mohd Idris, Yong Shih Mei, Shazana Rifham Abdullah, Norfashihah Faridus, Nur Azirah Md Yusof, Nur Najwa Farahin M Yusoff, Rahman Jamal, Aizai Azan Abdul Rahim, Abdul Kahar Abdul Ghapar, Ammu Kutty Radhakrishnan, Alan Yean Yip Fong, Omar Ismail, Saravanan Krishinan, Chuey Yan Lee, Liew Houng Bang, Eashwary Mageswaren, Kauthaman Mahendran, Nor Hanim Mohd Amin, Gunavathy Muthusamy, Aaron Ong Hean Jin, Ahmad Wazi Ramli, Noel Thomas Ross, Anwar Irawan Ruhani, Mansor Yahya, Yusniza Yusoff, Siti Khairani Zainal Abidin, Laryssa Amado, Thomas Bolton, Sophie Weston, Jason Crawte, Niko Ovenden, Ank Michielsen, Md Mostafa Monower, Wan Rozita Wan Mahiyuddin, Angela Wood, Emanuele Di Angelantonio, Nur Suffia Sulaiman, John Danesh, and Adam S Butterworth
Abstract: BACKGROUND Although the burden of premature myocardial infarction (MI) is high in Malaysia, direct evidence on the determinants of MI in this multi-ethnic population remains sparse. OBJECTIVE The Malaysian Acute Vascular Events Risk (MAVERIK) study is a retrospective case-control study established to investigate the genomic, lipid-related, and other determinants of acute MI in Malaysia. In this paper, we report the study protocol and early results. METHODS By June 2019, we had enrolled approximately 2500 patients with their first MI and 2500 controls without cardiovascular disease, who were frequency-matched by age, sex, and ethnicity, from 17 hospitals in Malaysia. For each participant, serum and whole blood have been collected and stored. Clinical, demographic, and behavioral information has been obtained using a 200-item questionnaire. RESULTS Tobacco consumption, a history of diabetes, hypertension, markers of visceral adiposity, indicators of lower socioeconomic status, and a family history of coronary disease were more prevalent in cases than in controls. Adjusted (age and sex) logistic regression models for traditional risk factors indicated that current smoking (odds ratio [OR] 4.11, 95% CI 3.56-4.75; PP=.001), a history of high blood pressure (OR 2.13, 95% CI 1.86-2.44; PPP=.009), and obesity (BMI >30 kg/m2; OR 1.19, 95% CI 1.05-1.34; P=.009) were associated with MI in age- and sex-adjusted models. CONCLUSIONS The MAVERIK study can serve as a useful platform to investigate genetic and other risk factors for MI in an understudied Southeast Asian population. It should help to hasten the discovery of disease-causing pathways and inform regionally appropriate strategies that optimize public health action. INTERNATIONAL REGISTERED REPORT RR1-10.2196/31885
Published: 2021
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22. A novel index-based decision support toolkit for safe reopening following a generalized lockdown in low and middle-income countries

Author: Sajedul Talukder, K. S. Ishtiaq, Abu S. Shonchoy, Rajiv Chowdhury, and Nasar U. Ahmed
Subjects: Decision support system, Index (economics), Coronavirus disease 2019 (COVID-19), genetic structures, Computer science, Science, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 030231 tropical medicine, Developing country, Diseases, World health, Article, Decision Support Techniques, 03 medical and health sciences, 0302 clinical medicine, Humans, Operations management, Computer Simulation, 030212 general & internal medicine, Developing Countries, Multidisciplinary, Health care, COVID-19, Restrictive interventions, Health care economics, Health policy, Low and middle income countries, Viral infection, Communicable Disease Control, Quarantine, Income, Medicine, Infectious diseases
Abstract: While the effectiveness of lockdowns to reduce Coronavirus Disease-2019 (COVID-19) transmission is well established, uncertainties remain on the lifting principles of these restrictive interventions. World Health Organization recommends case positive rate of 5% or lower as a threshold for safe reopening. However, inadequate testing capacity limits the applicability of this recommendation, especially in the low-income and middle-income countries (LMICs). To develop a practical reopening strategy for LMICs, in this study, we first identify the optimal timing of safe reopening by exploring accessible epidemiological data of 24 countries during the initial COVID-19 surge. We find that a safe opening can occur two weeks after the crossover of daily infection and recovery rates while maintaining a negative trend in daily new cases. Epidemiologic SIRM model-based example simulation supports our findings. Finally, we develop an easily interpretable large-scale reopening (LSR) index, which is an evidence-based toolkit—to guide/inform reopening decision for LMICs.
Published: 2021

23. A case report of nosocomial infection with SARS CoV-2 in a one-year old Meningoencephalitis patient in a tertiary hospital of Bangladesh

Author: Arifa Akram, Sohel Rahman, Reaz Chowdhury, Shahin Jewel, and Rajiv Chowdhury
Subjects: Pediatrics, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Unconsciousness, Meningoencephalitis, medicine.disease, Convulsion, Pandemic, medicine, medicine.symptom, business, Neck stiffness, Communicating hydrocephalus
Abstract: Introduction: Novel corona virus (SARS-Coronavirus-2: SARS-CoV-2) which emerged in Wuhan, China, has spread to multiple countries rapidly. Little information is known about nosocomial infections by SARS-CoV-2 in the initial period. As it spreads across the globe, physicians face the challenges of a contagious pandemic including patient isolation and diagnosis. Case Report: We report a case of concurrent meningoencephalitis and COVID-19 infection in a one-year old Bangladeshi patient who was brought a tertiary hospital in Dhaka, Bangladesh due to fever, convulsion and neck stiffness accompanied by unconsciousness later. Computed tomography (CT) SCAN of brain showed excessive encephalopathic change in both cerebral hemispheres with moderate communicating hydrocephalus, suggesting meningoencephalitis. During his hospitalization, he became infected with SARS-CoV-2 which was confirmed by real time polymerase chain reaction (RT-PCR. Conclusion: SARS-CoV-2 can be rapidly transmitted patient-to patient regardless of whether they have symptoms or not. Each hospital must differentiate patients with known or suspected COVID 19 infection from patients with a low probability COVID-19 infection in order to limit direct or indirect transmission.
Published: 2020
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24. The route of administration, timing, duration and dose of postmenopausal hormone therapy and cardiovascular outcomes in women: a systematic review

Author: Cristina Pellegrino Baena, Mahmuda Chadni, Sara Shahzad, Marija Glisic, Rajiv Chowdhury, Oscar H. Franco, Clare Oliver-Williams, Elizabeth Brown, Taulant Muka, Oliver-Williams, Clare [0000-0002-3573-2426], Chowdhury, Rajiv [0000-0003-4881-5690], and Apollo - University of Cambridge Repository
Subjects: cardiovascular risk, medicine.medical_specialty, medicine.medical_treatment, 610 Medicine & health, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Transdermal estrogen, 360 Social problems & social services, Internal medicine, medicine, Humans, Prospective Studies, coronary heart disease, Prospective cohort study, Stroke, Progesterone, 030219 obstetrics & reproductive medicine, hormone therapy, Estradiol, business.industry, Estrogen Replacement Therapy, Obstetrics and Gynecology, Estrogens, Thrombosis, Hormone replacement therapy (menopause), Venous Thromboembolism, Middle Aged, medicine.disease, Postmenopause, Menopause, Clinical trial, myocardial infarction, Reproductive Medicine, Cardiovascular Diseases, Female, Observational study, Hormone therapy, business
Abstract: BACKGROUND The effect of postmenopausal hormone therapy (HT) on cardiovascular disease (CVD) risk remains controversial. OBJECTIVE AND RATIONALE We aimed to systematically review the evidence regarding the role of dose, route of hormone administration, timing of initiation and duration of HT on cardiovascular risk among postmenopausal women. SEARCH METHODS The electronic databases Medline Ovid, Web of Science and Cochrane Central were systematically searched to identify studies published before 30 January 2018. Reference lists, using Elsevier's Scopus, of the included studies were searched for further identification of relevant studies. Clinical trials and observational studies that assessed clinical and subclinical cardiovascular outcomes in relation to dose, route of administration, duration of use, or timing of HT initiation among postmenopausal women were included. Data were extracted by independent reviewers using a pre-designed data collection form. The Cochrane Collaboration's tool and the Newcastle-Ottawa Scale were used by two independent investigators to assess the risk of bias in RCTs and in prospective observational studies, respectively. OUTCOMES In total, 33 unique studies (6 trials and 27 prospective observational studies) were identified, including a total of 2 588 327 women. The synthesis of the existing knowledge on this topic was challenging due to inconsistent findings between some studies, caused by substantial diversity in scientific rigor and quality across the available literature. Overall, the evidence did not support the concerns that oral or transdermal HT increases heart disease risk. Contrary, observational data showed that a beneficial cardioprotective effect can be observed even with use of low doses of oral HT (effect of 0.3 mg/day of oral conjugated equine estrogen was similar to that seen with the standard dose of 0.625 mg/day), but clinical trials to support a cardioprotective benefit of HT in primary prevention have not been identified. Furthermore, the current data suggested that oral and transdermal HT, in dose-dependent manner and irrespective of HT formulation, may increase thromboembolic risk, as well as risk of stroke. However, transdermal estrogen with 10 years since the menopause onset (>60 years old), due to greater absolute risks of coronary heart disease, stroke and venous thromboembolism, HT should be used for the shortest time possible and in lowest possible dose and preferably transdermal administration should be recommended. However, an individualized treatment approach including baseline CVD risk assessment should be applied when prescribing HT. The majority of studies included in the current review are from North American and European populations, which might limit the generalizability of the findings of this review to the other populations. Finally, the quality of evidence included in this review was generally low or moderate, highlighting a need for more rigorous research to help us better understand HT and cardiovascular health.
Published: 2018
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25. Safe Reopening Following Generalized Lockdowns: A Strategy Based on Evidence from 24 Worldwide Countries

Author: K. S. Ishtiaq, Sajedul Talukder, Rajiv Chowdhury, Nasar U. Ahmed, and Abu S. Shonchoy
Subjects: Risk analysis (engineering), Business
Abstract: While the effectiveness of lockdowns to reduce Coronavirus Disease-2019 (COVID-19) transmission is well established, uncertainties remain on the lifting principles of these restrictive interventions. World Health Organization recommends case positive rate of 5% or lower as a threshold for safe reopening. However, inadequate testing capacity limits the applicability of this recommendation, especially in the low-income and middle-income countries (LMICs). To develop a practical reopening strategy for LMICs, in this study, we first identify the optimal timing of safe reopening by exploring accessible epidemiological data of 24 countries during the initial COVID-19 surge. We find that safely reopening requires a two-week waiting period, after the crossover of daily infection and recovery rates – coupled with a post-crossover continuous negative trend in daily new cases. Epidemiologic SIRM model-based simulation analysis validates our findings. Finally, we develop an easily interpretable large-scale reopening (LSR) index, which is an evidence-based toolkit – to guide/inform the reopening decisions for LMICs.
Published: 2021
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26. Transethnic Transferability of a Genome-Wide Polygenic Score for Coronary Artery Disease

Author: Sekar Kathiresan, Yii-Der Ida Chen, Amanda Dobbyn, Judy H. Cho, Krishna G. Aragam, Wayne Huey-Herng Sheu, Harlan M. Krumholz, Stephen S. Rich, Rajiv Chowdhury, Akl C. Fahed, Jerome I. Rotter, George Hindy, Patrick T. Ellinor, Kumardeep Chaudhary, Ron Do, and Amit Khera
Subjects: Risk, Genetics, business.industry, Transferability, Black People, Hispanic or Latino, Coronary Artery Disease, General Medicine, medicine.disease, Genome, White People, Article, Coronary artery disease, Race (biology), Asian People, Meta-analysis, Polygenic score, Odds Ratio, medicine, Humans, business, Genome-Wide Association Study
Abstract: N/A
Published: 2021
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27. Stigma: the social virus spreading faster than COVID-19

Author: Rajiv Chowdhury, Kim Robin van Daalen, Oscar H. Franco, and Mark Cobain
Subjects: medicine.medical_specialty, Latin Americans, business.industry, Epidemiology, media_common.quotation_subject, Public health, Immigration, Public Health, Environmental and Occupational Health, Outbreak, Stigma (botany), 030209 endocrinology & metabolism, Disease, Criminology, 03 medical and health sciences, 0302 clinical medicine, Infectious disease (medical specialty), Pandemic, Medicine, 030212 general & internal medicine, business, media_common
Abstract: Novel epidemics and pandemics are inherently plagued by scientific uncertainties and a rapidly evolving nature. This can lead to widespread fear and confusion—directly proportional to the level of disease impact and subsequent media coverage, which perpetuates panic.1 Evolutionary psychologists argue that as response to fear humans tend to distance from those considered a source of danger (infections), guided by self-preservation, desire to find control or unfounded beliefs that those infected bear responsibility. Yet, this leads to misplaced reactions and stigmatisation.2 Originally from ancient Greek, the term ‘stigma’ was used to ‘permanently mark people as criminals, traitors or slaves’. Nowadays, it describes negative associations and discrimination against people with certain attributes (social, physical, behavioural).3 Examples of stigmatisation can be found throughout infectious disease history, affecting communities, caregivers, family and those infected. Among the most stigmatised have been those affected by or associated with HIV/AIDS.4 Many other examples exist, towards Jewish immigrants during the 1892 typhus fever and cholera outbreaks in New York City,1 towards ‘African-ness’ during Ebola outbreak(s), towards ‘Asian-ness’ during SARS4 and towards those of Mexican/Latin American descent during 2009 H1N1 …
Published: 2021
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28. Rare coding variants in 35 genes associate with circulating lipid levels – a multi-ancestry analysis of 170,000 exomes

Author: Marju Orho-Melander, Humberto García-Ortiz, Xueling Sim, Amp-T D-Genes, Cheol Joo Park, Gina M. Peloso, Jason Flannick, Brian Tomlinson, Hyun Min Kang, Emilio J. Cordova, Stephen S. Rich, Richard A. Gibbs, Angélica Martínez-Hernández, Lorena Orozco, Harsha Doddapaneni, Lisa R. Yanek, Jiwon Lee, Namrata Gupta, Valeriya Lyssenko, Sohee Han, James B. Meigs, Bong-Jo Kim, Bruce M. Psaty, Leslie S. Emery, Kerrin S. Small, Pradeep Natarajan, May E. Montasser, Christian Gieger, Sharon L.R. Kardia, Sarah C. Nelson, Craig L. Hanis, Heikki A. Koistinen, María Elena González-Villalpando, Edmund Chan, Michael Y. Tsai, Benjamin Glaser, Thomas Meitinger, Matthew J. Bown, Mariaelisa Graff, John Danesh, Sekar Kathiresan, Tiinamaija Tuomi, Ramachandran S. Vasan, Gil Atzmon, Alyna T. Khan, Diego Ardissino, Yii-Der Ida Chen, David Zhang, Rob M. van Dam, Wendy S. Post, Barry I. Freedman, D. C. Rao, Michael Preuss, Donna M. Lehman, L. Adrienne Cupples, Colin N. A. Palmer, Claudia H. T. Tam, Hortensia Moreno-Macías, Markku Laakso, Peter Dornbos, Teresa Tusié-Luna, Stella Aslibekyan, Marguerite R. Irvin, Daniel J. Rader, Jee-Young Moon, Eimear E. Kenny, Lisa W. Martin, Jennifer A. Brody, Amit Khera, Erwin P. Bottinger, Sarah E. Graham, Myriam Fornage, Ruth McPherson, Nancy L. Heard-Costa, Michael Boehnke, Clicerio Gonzalez, Ryan W. Kim, Yi-Cheng Chang, Peter M. Nilsson, Yik Ying Teo, Robert Sladek, Cristen J. Willer, Fei Fei Wang, Donna K. Arnett, Mark Chaffin, Karine A. Viaud Martinez, Alanna C. Morrison, Leslie A. Lange, Ravindranath Duggirala, Donna M. Muzny, Kent D. Taylor, Niels Grarup, Soren Germer, Patricia A. Peyser, Brian E. Cade, Lewis C. Becker, Steven A. Lubitz, Nicholette D. Palmer, Susan K. Dutcher, Ronald C.W. Ma, Xuenan Mi, Xiuqing Guo, Hugh Watkins, Eric Boerwinkle, Qibin Qi, Johanna Kuusisto, Christie M. Ballantyne, Tanika N. Kelly, Rajiv Chowdhury, Elvia Mendoza-Caamal, Wing-Yee So, Tien Yin Wong, Torben Hansen, Cecilia Contreras-Cubas, Jeong-Sun Seo, Mi Yeong Hwang, Daekwan Seo, Dajiang J. Liu, Cristina Revilla-Monsalve, Paul S. de Vries, Daniel R. Witte, Yi-Jen Hung, Olle Melander, Karen L. Mohlke, Lucinda Antonacci-Fulton, Francisco Barajas-Olmos, Soo Heon Kwak, Daniel E. Weeks, Claudia Schurmann, Ginger A. Metcalf, Young-Jin Kim, Adrienne M. Stilp, Lori L. Bonnycastle, John Blangero, Ralph A. DeFronzo, Donald W. Bowden, Rasika A. Mathias, Oluf Pedersen, Rozenn N. Lemaitre, Stephen T. McGarvey, Heribert Schunkert, Jaakko Tuomilehto, Farook Thameem, Valentin Fuster, Joshua C. Bis, George Hindy, Allan Linneberg, James G. Wilson, Kyong Soo Park, Sergio A. Islas-Andrade, Ching-Yu Cheng, Won Jung Choi, Minxian X. Wang, Xuzhi Wang, Adolfo Correa, Jai G. Broome, Gail P. Jarvik, Alexander P. Reiner, E. Shyong Tai, Juyoung Lee, Mark I. McCarthy, Nilesh J. Samani, Susan Redline, Carlos A. Aguilar-Salinas, Jerome I. Rotter, Ma. Eugenia Garay-Sevilla, Jiang He, Patrick T. Ellinor, Joseph Park, Joanne E. Curran, Nir Barzilai, Federico Centeno-Cruz, Seonwook Lee, Lawrence F. Bielak, Jianjun Liu, Charles Kooperberg, Juan M. Peralta, Jose C. Florez, Leif Groop, Noël P. Burtt, Margaret Sunitha Selvaraj, Jeffrey R. O'Connell, and Ruth J. F. Loos
Subjects: Genetics, 0303 health sciences, education.field_of_study, Population, Single-nucleotide polymorphism, Genome-wide association study, Biology, DNA sequencing, Minor allele frequency, 03 medical and health sciences, 0302 clinical medicine, SNP, education, Gene, 030217 neurology & neurosurgery, Exome sequencing, 030304 developmental biology
Abstract: Large-scale gene sequencing studies for complex traits have the potential to identify causal genes with therapeutic implications. We performed gene-based association testing of blood lipid levels with rare (minor allele frequency170,000 individuals from multiple ancestries: 97,493 European, 30,025 South Asian, 16,507 African, 16,440 Hispanic/Latino, 10,420 East Asian, and 1,182 Samoan. We identified 35 genes associated with circulating lipid levels. Ten of these: ALB, SRSF2, JAK2, CREB3L3, TMEM136, VARS, NR1H3, PLA2G12A, PPARG and STAB1 have not been implicated for lipid levels using rare coding variation in population-based samples. We prioritize 32 genes identified in array-based genome-wide association study (GWAS) loci based on gene-based associations, of which three: EVI5, SH2B3, and PLIN1, had no prior evidence of rare coding variant associations. Most of the associated genes showed evidence of association in multiple ancestries. Also, we observed an enrichment of gene-based associations for low-density lipoprotein cholesterol drug target genes, and for genes closest to GWAS index single nucleotide polymorphisms (SNP). Our results demonstrate that gene-based associations can be beneficial for drug target development and provide evidence that the gene closest to the array-based GWAS index SNP is often the functional gene for blood lipid levels.
Published: 2020
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29. An Adaptive Governance and Health System Response for the Covid-19 Emergency

Author: Rajiv Chowdhury, Pallavi Roy, Mehnaz Rabbani, Mushtaq Khan, and Imran Matin
Subjects: Economics and Econometrics, Sociology and Political Science, Computer science, 050204 development studies, Corporate governance, 05 social sciences, Geography, Planning and Development, Feasible region, Developing country, Adaptive response, Development, Letters on Urgent Issues, Risk analysis (engineering), Work (electrical), Order (exchange), Scale (social sciences), 0502 economics and business, 050207 economics, Set (psychology)
Abstract: In the absence of an efficacious and affordable vaccine, the current crisis of COVID-19 is likely to be a long drawn one for many developing countries. In Bangladesh, where the entire population is susceptible and strict lockdown has been relaxed (as of May 31st 2020) due to concerns over saving livelihoods, the best available resources and capacities in the country have to be mobilized for an integrated and adaptive response strategy. In this paper we argue that a suitable response strategy for a country with highly constrained health system, must consider how response components will be delivered at scale, along with what can be delivered. In order to save maximum number of lives, an optimal strategy will be one that is able to iteratively select the most feasible set of health response and the network of organizations that can deliver most effectively at scale. This might require thinking outside of the conventional vertical network of public health system. Given its history of high-capacity non-government organizations in Bangladesh, it is likely that there are multiple alternative horizontal network options for delivering any set of response interventions. In fact many horizontal networks are already actively engaged in COVID-19 response work. The goal should be to identify and coordinate these networks, create new networks, and embed mechanisms for scaling up what works and scaling down what does not work. For a rapidly escalating and unpredictable crisis such as COVID-19, an adaptive response strategy is needed which allows for old and new networks of organizations to align and work collectively with minimum loss of lives.
Published: 2020

30. Cardiometabolic Health: Key in Reducing Adverse COVID-19 Outcomes

Author: Oscar H. Franco, Kim Robin van Daalen, Rajiv Chowdhury, and Apollo - University of Cambridge Repository
Subjects: medicine.medical_specialty, 2019-20 coronavirus outbreak, lcsh:Diseases of the circulatory (Cardiovascular) system, Invited Editorial, Coronavirus disease 2019 (COVID-19), Epidemiology, Adverse outcomes, media_common.quotation_subject, Health Behavior, Pneumonia, Viral, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Hygiene, Environmental health, Pandemic, medicine, Humans, Healthy Lifestyle, 030212 general & internal medicine, Pandemics, media_common, Metabolic Syndrome, Community and Home Care, business.industry, Public health, lcsh:Public aspects of medicine, public health, lcsh:RA1-1270, Limiting, Public Health, Preventive medicine, Cardiovascular Health, covid-19, Cardiovascular Diseases, lcsh:RC666-701, Practice Guidelines as Topic, Health behavior, Coronavirus Infections, Cardiology and Cardiovascular Medicine, business, COVID-19, cardiometabolic health
Abstract: Whilst current public health measures focused on good hygiene practices and limiting person-to-person transmission contribute effectively in managing the COVID-19 pandemic, they will not prevent all individuals from becoming infected. Thus, it is of importance to explore what individuals could do to mitigate adverse outcomes. The value of beneficial health behaviours and a healthy lifestyle to improve immune functioning and lower adverse consequences of COVID-19 are increasingly being emphasized. Here we discuss seven key health behaviours and corresponding recommendations that may assist in reducing unfavourable COVID-19 outcomes.
Published: 2020

31. Insufficient Sun Exposure Has Become a Real Public Health Problem

Author: Richard Weller, Pelle G. Lindqvist, Frank R. de Gruijl, Cedric F. Garland, Ramune Jacobsen, David G. Hoel, Prue H. Hart, David J. Llewellyn, Rajiv Chowdhury, Martin Feelisch, Henning Tiemeier, Lars Alfredsson, Antony R. Young, D. Allan Butterfield, Bruce K. Armstrong, Butterfield, D Allan [0000-0003-3254-5286], Hart, Prue H [0000-0001-7207-6467], Hoel, David G [0000-0002-1178-1610], Jacobsen, Ramune [0000-0002-8142-9807], Lindqvist, Pelle G [0000-0002-1652-8235], Weller, Richard B [0000-0003-2550-9586], and Apollo - University of Cambridge Repository
Subjects: medicine.medical_specialty, Ultraviolet Rays, Health, Toxicology and Mutagenesis, lcsh:Medicine, Sunburn, vitamin D, Disease, Review, UV radiation, 030207 dermatology & venereal diseases, 03 medical and health sciences, sun exposure, 0302 clinical medicine, Breast cancer, nitric oxide, Environmental health, medicine, Vitamin D and neurology, Humans, Asthma, Type 1 diabetes, integumentary system, business.industry, Public health, lcsh:R, disease prevention, Public Health, Environmental and Occupational Health, medicine.disease, Vitamin D Deficiency, Europe, Sunlight, Public Health, Metabolic syndrome, business, 030217 neurology & neurosurgery
Abstract: This article aims to alert the medical community and public health authorities to accumulating evidence on health benefits from sun exposure, which suggests that insufficient sun exposure is a significant public health problem. Studies in the past decade indicate that insufficient sun exposure may be responsible for 340,000 deaths in the United States and 480,000 deaths in Europe per year, and an increased incidence of breast cancer, colorectal cancer, hypertension, cardiovascular disease, metabolic syndrome, multiple sclerosis, Alzheimer’s disease, autism, asthma, type 1 diabetes and myopia. Vitamin D has long been considered the principal mediator of beneficial effects of sun exposure. However, oral vitamin D supplementation has not been convincingly shown to prevent the above conditions; thus, serum 25(OH)D as an indicator of vitamin D status may be a proxy for and not a mediator of beneficial effects of sun exposure. New candidate mechanisms include the release of nitric oxide from the skin and direct effects of ultraviolet radiation (UVR) on peripheral blood cells. Collectively, this evidence indicates it would be wise for people living outside the tropics to ensure they expose their skin sufficiently to the sun. To minimize the harms of excessive sun exposure, great care must be taken to avoid sunburn, and sun exposure during high ambient UVR seasons should be obtained incrementally at not more than 5–30 min a day (depending on skin type and UV index), in season-appropriate clothing and with eyes closed or protected by sunglasses that filter UVR.
Published: 2020
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32. Dynamic interventions to control COVID-19 pandemic: a multivariate prediction modelling study comparing 16 worldwide countries

Author: Daniel D. Reidpath, Shajedur Rahman Shawon, Carolina Ochoa-Rosales, Shamini Prathapan, Oscar H. Franco, Nathalia Gonzalez-Jaramillo, Rajiv Chowdhury, Kevin Heng, Daisy Okonofua, Gabriel Goh, Christian L. Althaus, Valentina Gonzalez-Jaramillo, Abbas Bhuiya, Sara Shahzad, Chowdhury, Rajiv [0000-0003-4881-5690], Apollo - University of Cambridge Repository, and Epidemiology
Subjects: 0301 basic medicine, medicine.medical_specialty, Epidemiology, 530 Physics, Pneumonia, Viral, Psychological intervention, 610 Medicine & health, Disease, law.invention, Betacoronavirus, 03 medical and health sciences, 0302 clinical medicine, law, 360 Social problems & social services, Pandemic, Humans, Medicine, 030212 general & internal medicine, Intensive care medicine, Pandemics, Dynamic interventions, Infectious disease, SARS-CoV-2, business.industry, Social distance, Public health, 520 Astronomy, COVID-19, Models, Theoretical, 500 Science, Intensive care unit, 3. Good health, Coronavirus, 030104 developmental biology, Communicable Disease Control, Prediction modelling, Coronavirus Infections, business, Basic reproduction number
Abstract: 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 (R0) 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. Electronic supplementary material The online version of this article (10.1007/s10654-020-00649-w) contains supplementary material, which is available to authorized users.
Published: 2020
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33. Association of plasma biomarkers of fruit and vegetable intake with incident type 2 diabetes : EPIC-InterAct case-cohort study in eight European countries

Author: Matthias B. Schulze, Peter M. Nilsson, Sara Grioni, Rosario Tumino, Stephen J. Sharp, Salvatore Panico, Ju-Sheng Zheng, Heiner Boeing, Tilman Kühn, Dagfinn Aune, Nita G. Forouhi, Kim Overvad, Olov Rolandsson, Miren Dorronsoro, Antonio Agudo, Fulvio Ricceri, Giovanna Masala, Thomas E. Gundersen, Paul W. Franks, Rajiv Chowdhury, Guy Fagherazzi, Tammy Y.N. Tong, Aurelio Barricarte, Anne Tjønneland, Nicholas J. Wareham, Ivonne Sluijs, Heinz Freisling, Kay-Tee Khaw, Annemieke M.W. Spijkerman, María Dolores Chirlaque, Adam S. Butterworth, Keren Papier, Elio Riboli, Verena Katzke, Fumiaki Imamura, John Danesh, Cecilie Kyrø, Elisabete Weiderpass, Marc J. Gunter, Nasser Laouali, J. Ramón Quirós, Yvonne T. van der Schouw, Daniel Redondo-Sanchez, Marinka Steur, Douae El-Fatouhi, Forouhi, Nita G [0000-0002-5041-248X], and Apollo - University of Cambridge Repository
Subjects: Male, Type 2 diabetes, Ascorbic Acid, MELLITUS, 0302 clinical medicine, Vegetables, 030212 general & internal medicine, Prospective Studies, LEVEL CORRELATIONS, Prospective cohort study, health care economics and organizations, RISK, Diabetis, GUT MICROBIOTA, Diabetes, Biochemical markers, Hazard ratio, Absolute risk reduction, General Medicine, CANCER, European Prospective Investigation into Cancer and Nutrition, Europe, CARDIOVASCULAR-DISEASE, Marcadors bioquímics, Endokrinologi och diabetes, Female, HEALTH, Life Sciences & Biomedicine, Type 2, Cohort study, 030209 endocrinology & metabolism, Endocrinology and Diabetes, 1117 Public Health and Health Services, 03 medical and health sciences, Medicine, General & Internal, General & Internal Medicine, Diabetes Mellitus, medicine, Humans, METAANALYSIS, Science & Technology, VITAMIN-C, business.industry, Research, 1103 Clinical Sciences, Biomarkers, Carotenoids, Case-Control Studies, Diabetes Mellitus, Type 2, Diet, Fruit, medicine.disease, Ascorbic acid, Confidence interval, business, BETA-CAROTENE SUPPLEMENTATION, Demography
Abstract: Objective To investigate the association of plasma vitamin C and carotenoids, as indicators of fruit and vegetable intake, with the risk of type 2 diabetes. Design Prospective case-cohort study. Setting Populations from eight European countries. Participants 9754 participants with incident type 2 diabetes, and a subcohort of 13 662 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort of 340 234 participants: EPIC-InterAct case-cohort study. Main outcome measure Incident type 2 diabetes. Results In a multivariable adjusted model, higher plasma vitamin C was associated with a lower risk of developing type 2 diabetes (hazard ratio per standard deviation 0.82, 95% confidence interval 0.76 to 0.89). A similar inverse association was shown for total carotenoids (hazard ratio per standard deviation 0.75, 0.68 to 0.82). A composite biomarker score (split into five equal groups), comprising vitamin C and individual carotenoids, was inversely associated with type 2 diabetes with hazard ratios 0.77, 0.66, 0.59, and 0.50 for groups 2-5 compared with group 1 (the lowest group). Self-reported median fruit and vegetable intake was 274 g/day, 396 g/day, and 508 g/day for participants in categories defined by groups 1, 3, and 5 of the composite biomarker score, respectively. One standard deviation difference in the composite biomarker score, equivalent to a 66 (95% confidence interval 61 to 71) g/day difference in total fruit and vegetable intake, was associated with a hazard ratio of 0.75 (0.67 to 0.83). This would be equivalent to an absolute risk reduction of 0.95 per 1000 person years of follow up if achieved across an entire population with the characteristics of the eight European countries included in this analysis. Conclusions These findings indicate an inverse association between plasma vitamin C, carotenoids, and their composite biomarker score, and incident type 2 diabetes in different European countries. These biomarkers are objective indicators of fruit and vegetable consumption, and suggest that diets rich in even modestly higher fruit and vegetable consumption could help to prevent development of type 2 diabetes.
Published: 2020
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34. A 24-step guide on how to design, conduct, and successfully publish a systematic review and meta-analysis in medical research

Author: Jelena Milic, Wichor M. Bramer, Sanne Verhoog, Marija Glisic, Rajiv Chowdhury, Oscar H. Franco, Taulant Muka, Julia Bohlius, Epidemiology, and Erasmus MC other
Subjects: Epidemiology, business.industry, Process (engineering), Management science, media_common.quotation_subject, Guidelines as Topic, 030204 cardiovascular system & hematology, 03 medical and health sciences, Identification (information), 0302 clinical medicine, Systematic review, Meta-Analysis as Topic, Meta-analysis, Health care, Humans, Medicine, Observational study, Quality (business), 030212 general & internal medicine, business, 610 Medicine & health, 360 Social problems & social services, Systematic Reviews as Topic, Medical literature, media_common
Abstract: To inform evidence-based practice in health care, guidelines and policies require accurate identification, collation, and integration of all available evidence in a comprehensive, meaningful, and time-efficient manner. Approaches to evidence synthesis such as carefully conducted systematic reviews and meta-analyses are essential tools to summarize specific topics. Unfortunately, not all systematic reviews are truly systematic, and their quality can vary substantially. Since well-conducted evidence synthesis typically involves a complex set of steps, we believe formulating a cohesive, step-by-step guide on how to conduct a systemic review and meta-analysis is essential. While most of the guidelines on systematic reviews focus on how to report or appraise systematic reviews, they lack guidance on how to synthesize evidence efficiently. To facilitate the design and development of evidence syntheses, we provide a clear and concise, 24-step guide on how to perform a systematic review and meta-analysis of observational studies and clinical trials. We describe each step, illustrate it with concrete examples, and provide relevant references for further guidance. The 24-step guide (1) simplifies the methodology of conducting a systematic review, (2) provides healthcare professionals and researchers with methodologically sound tools for conducting systematic reviews and meta-analyses, and (3) it can enhance the quality of existing evidence synthesis efforts. This guide will help its readers to better understand the complexity of the process, appraise the quality of published systematic reviews, and better comprehend (and use) evidence from medical literature.
Published: 2020
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35. Lifting the lockdown: what are the options for low and middle-income countries?

Author: Nusrat Khan, Rajiv Chowdhury, Oscar H. Franco, Imran Matin, Sohel Reza Choudhury, and Shammi Luhar
Subjects: medicine.medical_specialty, SocArXiv|Social and Behavioral Sciences|Public Affairs, Public Policy and Public Administration|Health Policy, Exit strategy, Coronavirus disease 2019 (COVID-19), Public economics, bepress|Social and Behavioral Sciences|Economics, bepress|Social and Behavioral Sciences|Economics|Health Economics, SocArXiv|Social and Behavioral Sciences|International and Area Studies, Public health, Social distance, SocArXiv|Social and Behavioral Sciences|Economics, Psychological intervention, SocArXiv|Social and Behavioral Sciences|Public Affairs, Public Policy and Public Administration, Balance (accounting), Low and middle income countries, Economic cost, bepress|Social and Behavioral Sciences|Public Affairs, Public Policy and Public Administration|Health Policy, bepress|Social and Behavioral Sciences, medicine, bepress|Social and Behavioral Sciences|International and Area Studies, SocArXiv|Social and Behavioral Sciences|Economics|Health Economics, bepress|Social and Behavioral Sciences|Public Affairs, Public Policy and Public Administration, SocArXiv|Social and Behavioral Sciences, Business
Abstract: To limit the social, economic and psychological damage caused by strict social distancing interventions, many low and middle-income countries (LMICs) are seeking to ease restrictions. However, it is unknown what a ‘safe reopening’ entails in LMICs given suboptimal diagnostic and surveillance capabilities. Here we discuss three community-based public health measures (sustained mitigation, zonal lockdown and dynamic rolling lockdowns) which seek to adequately balance the public health and economic priorities. Each of these options have limitations and prerequisites that may be context-specific and should be considered before implementation, including implementation and maintenance costs, social and economic costs, context-specific epidemic growth and the existing health resources.
Published: 2020
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36. Lifestyle factors, cardiovascular disease and all-cause mortality in middle-aged and elderly women: a systematic review and meta-analysis

Author: Rosanne Freak-Poli, Gabriella M. van Dijk, Maryam Kavousi, Cristina Pellegrino Baena, Ziba Farajzadegan, Loes Jaspers, Gilson G. Viana Veloso, Klodian Dhana, Verônica Colpani, Rajiv Chowdhury, Taulant Muka, Oscar H. Franco, Trudy Voortman, Myrte J. Tielemans, and Epidemiology
Subjects: medicine.medical_specialty, Epidemiology, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Cause of Death, Internal medicine, medicine, Risk of mortality, Humans, Obesity, 030212 general & internal medicine, Prospective cohort study, Exercise, Life Style, Aged, business.industry, Incidence (epidemiology), Middle Aged, medicine.disease, Stroke, Menopause, Cardiovascular Diseases, Meta-analysis, Relative risk, Female, business, Risk Reduction Behavior
Abstract: Cardiovascular disease (CVD) risk factors, incidence and death increases from around the time of menopause comparing to women in reproductive age. A healthy lifestyle can prevent CVD, but it is unclear which lifestyle factors may help maintain and improve cardiovascular health for women after menopausal transition. We conducted a systematic review and meta-analysis of prospective cohort studies to evaluate the association between modifiable lifestyle factors (specifically smoking, physical activity, alcohol intake, and obesity), with CVD and mortality in middle-aged and elderly women. Pubmed, Embase, among other databases and reference lists were searched until February 29th, 2016. Study specific relative risks (RR) were meta-analyzed using random effect models. We included 59 studies involving 5,358,902 women. Comparing current versus never smokers, pooled RR were 3.12 (95% CI 2.15–4.52) for CHD incidence, 2.09 (95% CI 1.51–2.89) for stroke incidence, 2.76 (95% CI 1.62–4.71) for CVD mortality and 2.22 (95% CI 1.92–2.57) for all-cause mortality. Physical activity was associated with a decreased risk of 0.74 (95% CI 0.67–0.80) for overall CVD, 0.71 (95% CI 0.67–0.75) for CHD, 0.77 (95% CI 0.70–0.85) for stroke, 0.70 (95% CI 0.58–0.84) for CVD mortality and 0.71 (95% CI 0.65–0.78) for all-cause mortality. Comparing moderate drinkers versus non-drinkers, the RR was 0.72 (95% CI 0.56–0.91) for CHD, 0.63 (95% CI 0.57–0.71) for CVD mortality and 0.80 (95% CI 0.76–0.84) for all-cause mortality. For women with BMI 30–35 kg/m2 the risk was 1.67 (95% CI 1.24–2.25) for CHD and 2.3 (95% CI 1.56–3.40) for CVD mortality, compared to normal weight. Each 5 kg/m2 increase in BMI was associated with 24% (95% CI 16–33%) higher risk for all-cause mortality. This meta-analysis suggests that physical activity and moderate alcohol intake were associated with a reduced risk for CVD and mortality. Smoking and higher BMI were associated with an increased risk of these endpoints. Adherence to a healthy lifestyle may substantially lower the burden of CVD and reduce the risk of mortality among middle-aged and elderly women. However, this review highlights important gaps, as lack of standardized methods in assessing lifestyle factors and lack of accurate information on menopause status, which should be addressed by future studies in order to understand the role of menopause on the association between lifestyle factors and cardiovascular events.
Published: 2018
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37. Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use

Author: Michael Boehnke, Anke R. Hammerschlag, Stavroula Kanoni, Nilesh J. Samani, Stefan Blankenberg, Arpana Agrawal, Ersin Yavas, Chris Hsu, Dominique Arveiler, Giovanni Veronesi, Sarah E. Harris, Guillaume Lettre, Leah Wetherill, Helen R. Warren, M Samuel, Manav Kapoor, Praveen Surendran, Mengzhen Liu, Massimo Mangino, Abdulla Al Shafi Majumder, Chiara Batini, Jeff Haessler, Anton J. M. De Craen, Matt McGue, Laura J. Bierut, Yi Ling Chou, Markku Laakso, Ian J. Deary, Rebecca Rohde, Nhung Le, David Schlessinger, J. Dylan Weissenkampen, Claudia Langenberg, Tim D. Spector, Paul W. Franks, John P. Rice, Philippe M. Frossard, Hanieh Yaghootkar, Janie Corley, Frank Kee, J. Wouter Jukema, Pim van der Harst, Dermot F. Reily, Jenny Chang-Claude, Nicholas G. Martin, Tatiana Foroud, Sune F. Nielsen, Charles Kooperberg, Rudolf A. de Boer, Francesco Cucca, Paul D.P. Pharoah, Alex P. Reiner, Daniel R. Barnes, Anders Mälarstig, Jonathan Marten, Henry Völzke, Yu Jiang, Jukka Kontto, J Danesh, Antonis C. Antoniou, Andrew C. Heath, Nicholas J. Wareham, Joanna M. M. Howson, Alison Goate, Olov Rolandsson, Frida Renström, Chu Chen, Vinicius Tragante, Matt J. Neville, Kathleen Stirrups, Clemens Baumbach, Colin N. A. Palmer, Adam S. Butterworth, William G. Iacono, Naveed Sattar, Ian P. Hall, Daniel O. Stram, Giorgio Pistis, Jan-Håkan Jansson, Jaakko Kaprio, David R. Weir, David P. Strachan, Martin D. Tobin, Folkert W. Asselbergs, John M. Starr, Stefan Weiss, Thomas F. Vogt, Riccardo E. Marioni, Maarten Hoek, Jessica Tyrrell, Hilary A. Tindle, Alison M. Dunning, Anu Loukola, Joe Dennis, Victoria E. Jackson, Louise V. Wain, Eleftheria Zeggini, Weihua Zhang, Yaming Shao, Kari Kuulasmaa, Elisabeth Altmaier, Jean-Claude Tardif, Jian Gong, A. Mesut Erzurumluoglu, Andries R. van der Leij, Kari E. North, Anna F. Dominiczak, Martina Müller-Nurasyid, Scott I. Vrieze, Sarah Bertelsen, Markus Perola, Evangelos Evangelou, Chris J. Packard, Gonçalo R. Abecasis, Robert A. Scott, S. Trompet, Jennifer A. Smith, H. Steven Scholte, Timothy M. Frayling, Danielle Posthuma, Ian Ford, Douglas F. Easton, Børge Grønne Nordestgaard, Michiel L. Bots, Charles B. Eaton, Sharon L.R. Kardia, Dewan S. Alam, Xiaowei Zhan, Sean P. David, Maria Uria-Nickelsen, Dongbing Lai, Ilonca Vaartjes, Mark J. Caulfield, Valérie Turcot, Jean Ferrières, Emanuele Di Angelantonio, Robin Young, Pamela A. F. Madden, Tibor V. Varga, Asif Rasheed, Peter van der Meer, Dajiang J. Liu, Ioanna Tachmazidou, Panos Deloukas, Danish Saleheen, Evelin Mihailov, Caroline Hayward, Patricia B. Munroe, Beenish Qaiser, Jessica D. Faul, John C. Chambers, Matthias Nauck, Niek Verweij, Jordan M. Hughey, Christopher A. Haiman, Hans J. Grabe, Muriel Caslake, Saima Afaq, Jaspal S. Kooner, Tinca J. C. Polderman, Philippe Amouyel, Wei Zhao, Göran Hallmans, Andres Metspalu, Jarmo Virtamo, Carl A. Melbourne, Kaixin Zhou, Christiaan de Leeuw, Peter S. Sever, Eirini Marouli, Neil Poulter, Rajiv Chowdhury, Jian'an Luan, Deborah J. Thompson, F Karpe, Kyriaki Michailidou, David M. Brazel, Heather M. Stringham, Brein en Cognitie (Psychologie, FMG), Psychology Other Research (FMG), Human genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Reproduction & Development (AR&D), Cardiovascular Centre (CVC), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), Graduate School, Experimental Vascular Medicine, ACS - Diabetes & metabolism, Amsterdam Cardiovascular Sciences, ACS - Atherosclerosis & ischemic syndromes, AGEM - Digestive immunity, AGEM - Endocrinology, metabolism and nutrition, Laboratory Genetic Metabolic Diseases, Gastroenterology and Hepatology, Experimental Immunology, Radiotherapy, Cardiology, HUSLAB, Institute for Molecular Medicine Finland, Department of Public Health, Genetic Epidemiology, Barnes, Daniel [0000-0002-3781-7570], Erzurumluoglu, Mesut [0000-0003-1322-8138], Apollo - University of Cambridge Repository, Biological Psychology, and Complex Trait Genetics
Subjects: 0301 basic medicine, Nonsynonymous substitution, Genome-wide association study, 3124 Neurology and psychiatry, 0302 clinical medicine, DEPENDENCE, Genotype, Databases, Genetic, SEQUENCE VARIANTS, GWAS, Exome, Non-U.S. Gov't, Oligonucleotide Array Sequence Analysis, Genetics, RISK, HERITABILITY, Research Support, Non-U.S. Gov't, Smoking, ASSOCIATION, 3. Good health, ADH1B, Phenotype, Behavioral genetics, LOW-FREQUENCY, Alcohol, Heritability, Nicotine, Tobacco, Alcohol Drinking, Non-P.H.S, Single-nucleotide polymorphism, Biology, Research Support, Polymorphism, Single Nucleotide, N.I.H, 03 medical and health sciences, Research Support, N.I.H., Extramural, SDG 3 - Good Health and Well-being, Genetic variation, Journal Article, Humans, Genetic Predisposition to Disease, COMMON, Biological Psychiatry, 3112 Neurosciences, Genetic Variation, Extramural, MISSENSE VARIANTS, R1, Genetic architecture, 030104 developmental biology, U.S. Gov't, 030217 neurology & neurosurgery, Research Support, U.S. Gov't, Non-P.H.S, Genome-Wide Association Study
Abstract: BackgroundSmoking and alcohol use have been associated with common genetic variants in multiple loci. Rare variants within these loci hold promise in the identification of biological mechanisms in substance use. Exome arrays and genotype imputation can now efficiently genotype rare nonsynonymous and loss of function variants. Such variants are expected to have deleterious functional consequences and to contribute to disease risk.MethodsWe analyzed ∼250,000 rare variants from 16 independent studies genotyped with exome arrays and augmented this dataset with imputed data from the UK Biobank. Associations were tested for five phenotypes: cigarettes per day, pack-years, smoking initiation, age of smoking initiation, and alcoholic drinks per week. We conducted stratified heritability analyses, single-variant tests, and gene-based burden tests of nonsynonymous/loss-of-function coding variants. We performed a novel fine-mapping analysis to winnow the number of putative causal variants within associated loci.ResultsMeta-analytic sample sizes ranged from 152,348 to 433,216, depending on the phenotype. Rare coding variation explained 1.1% to 2.2% of phenotypic variance, reflecting 11% to 18% of the total single nucleotide polymorphism heritability of these phenotypes. We identified 171 genome-wide associated loci across all phenotypes. Fine mapping identified putative causal variants with double base-pair resolution at 24 of these loci, and between three and 10 variants for 65 loci. Twenty loci contained rare coding variants in the 95% credible intervals.ConclusionsRare coding variation significantly contributes to the heritability of smoking and alcohol use. Fine-mapping genome-wide association study loci identifies specific variants contributing to the biological etiology of substance use behavior.
Published: 2019
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38. Arsenic

Author: Rajiv, Chowdhury and Kim, van Daalen
Subjects: Young Adult, Cardiovascular Diseases, Humans, Heart, Ventricular Function, Left, Article, Arsenic
Abstract: BACKGROUND: Arsenic exposure has been related to numerous adverse cardiovascular outcomes. The aim of this study was to investigate the cross-sectional and prospective association between arsenic exposure with echocardiographic measures of left ventricular (LV) geometry and functioning. METHODS: A total of 1337 young adult participants free of diabetes mellitus and cardiovascular disease were recruited from the SHFS (Strong Heart Family Study). The sum of inorganic and methylated arsenic concentrations in urine (ΣAs) at baseline was used as a biomarker of arsenic exposure. LV geometry and functioning were assessed using transthoracic echocardiography at baseline and follow-up. RESULTS: Mean follow-up was 5.6 years, and median (interquartile range) of ΣAs was 4.2 (2.8–6.9) μg/g creatinine. Increased arsenic exposure was associated with prevalent LV hypertrophy, with an odds ratio (95% CI) per a 2-fold increase in ΣAs of 1.47 (1.05–2.08) in all participants and of 1.58 (1.04–2.41) among prehypertensive or hypertensive individuals. Measures of LV geometry, including LV mass index, left atrial systolic diameter, interventricular septum, and LV posterior wall thickness, were positively and significantly related to arsenic exposure. Among measures of LV functioning, stroke volume, and ejection fraction were associated with arsenic exposure. CONCLUSIONS: Arsenic exposure was related to an increase in LV wall thickness and LV hypertrophy in young American Indians with a low burden of cardiovascular risk factors. The relationship was stronger in participants with prehypertension or hypertension, suggesting that potential cardiotoxic effects of arsenic might be more pronounced in individuals already undergoing cardiovascular adaptive mechanisms following elevated systemic blood pressure.
Published: 2019

39. Arsenic

Author: Kim Robin van Daalen and Rajiv Chowdhury
Subjects: chemistry, business.industry, Environmental chemistry, Medicine, chemistry.chemical_element, Radiology, Nuclear Medicine and imaging, Cardiology and Cardiovascular Medicine, business, Arsenic
Published: 2019
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40. The role of DNA methylation and histone modifications in blood pressure: a systematic review

Author: A.H. Jan Danser, Rajiv Chowdhury, Oscar H. Franco, Wichor M. Bramer, Taulant Muka, Trudy Voortman, Jana Nano, Valentina Gonzalez-Jaramillo, Marija Glisic, Anton J.M. Roks, Eliana Portilla-Fernandez, Epidemiology, Erasmus MC other, and Internal Medicine
Subjects: Male, Blood Pressure, 030204 cardiovascular system & hematology, Bioinformatics, Epigenesis, Genetic, EHMT2, Histones, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal Medicine, Medicine, Humans, Genetic Predisposition to Disease, 030212 general & internal medicine, Epigenetics, 610 Medicine & health, Genetic Association Studies, biology, business.industry, Methylation, DNA Methylation, medicine.disease, Chromatin Assembly and Disassembly, Histone, Blood pressure, Phenotype, Pathophysiology of hypertension, DNA methylation, Hypertension, biology.protein, Female, business, Homeostasis, 360 Social problems & social services
Abstract: Epigenetic mechanisms might play a role in the pathophysiology of hypertension, a major risk factor for cardiovascular disease and renal failure. We aimed to systematically review studies investigating the association between epigenetic marks (global, candidate-gene or genome-wide methylation of DNA, and histone modifications) and blood pressure or hypertension. Five bibliographic databases were searched until the 7th of December 2018. Of 2984 identified references, 26 articles based on 25 unique studies met our inclusion criteria, which involved a total of 28,382 participants. The five studies that assessed global DNA methylation generally found lower methylation levels with higher systolic blood pressure, diastolic blood pressure, and/or presence of hypertension. Eighteen candidate-gene studies reported, in total, 16 differentially methylated genes, including renin-angiotensin-system-related genes (ACE promoter and AGTR1) and genes involved in sodium homeostasis and extracellular fluid volume maintenance system (NET promoter, SCNN1A, and ADD1). Between the three identified epigenome-wide association studies (EWAS), lower methylation levels of SULF1, EHMT2, and SKOR2 were found in hypertensive patients as compared with normotensive subjects, and lower methylation levels of PHGDH, SLC7A11, and TSPAN2 were associated with higher systolic and diastolic blood pressure. In summary, the most convincing evidence has been reported from candidate-gene studies, which show reproducible epigenetic changes in the interconnected renin-angiotensin and inflammatory systems. Our study highlights gaps in the literature on the role of histone modifications in blood pressure and the need to conduct high-quality studies, in particular, hypothesis-generating studies that may help to elucidate new molecular mechanisms.
Published: 2019
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41. Epigenetics and Inflammatory Markers: A Systematic Review of the Current Evidence

Author: Tamar Nijsten, Rajiv Chowdhury, Valentina Gonzalez-Jaramillo, Mohsen Ghanbari, Oscar H. Franco, Trudy Voortman, Abbas Dehghan, Marija Glisic, Eliana Portilla-Fernandez, Wichor M. Bramer, Jana Nano, Gonzalez-Jaramillo, Valentina [0000-0002-2470-7022], Portilla-Fernandez, Eliana [0000-0003-4105-8586], Apollo - University of Cambridge Repository, Epidemiology, Erasmus MC other, Dermatology, Voortman, Trudy [0000-0003-2830-6813], Bramer, Wichor [0000-0003-2681-9180], and Chowdhury, Rajiv [0000-0003-4881-5690]
Subjects: 0301 basic medicine, Candidate gene, Article Subject, Biomedical, Inflammation, 610 Medicine & health, Review Article, Bioinformatics, Genome, 03 medical and health sciences, 0302 clinical medicine, Basic Science, 360 Social problems & social services, medicine, lcsh:Pathology, Genetics, Immunology and Allergy, 2.1 Biological and endogenous factors, Epigenetics, Gene, Genetic association, 0604 Genetics, biology, Human Genome, 030104 developmental biology, Histone, FOS: Biological sciences, DNA methylation, biology.protein, medicine.symptom, 030217 neurology & neurosurgery, lcsh:RB1-214
Abstract: Epigenetic mechanisms have been suggested to play a role in the genetic regulation of pathways related to inflammation. Therefore, we aimed to systematically review studies investigating the association between DNA methylation and histone modifications with circulatory inflammation markers in blood. Five bibliographic databases were screened until 21 November of 2017. We included studies conducted on humans that examined the association between epigenetic marks (DNA methylation and/or histone modifications) and a comprehensive list of inflammatory markers. Of the 3,759 identified references, 24 articles were included, involving, 17,399 individuals. There was suggestive evidence for global hypomethylation but better-quality studies in the future have to confirm this. Epigenome-wide association studies (EWAS) (n=7) reported most of the identified differentially methylated genes to be hypomethylated in inflammatory processes. Candidate genes studies reported 18 differentially methylated genes related to several circulatory inflammation markers. There was no overlap in the methylated sites investigated in candidate gene studies and EWAS, except for TMEM49, which was found to be hypomethylated with higher inflammatory markers in both types of studies. The relation between histone modifications and inflammatory markers was assessed by one study only. This review supports an association between epigenetic marks and inflammation, suggesting hypomethylation of the genome. Important gaps in the quality of studies were reported such as inadequate sample size, lack of adjustment for relevant confounders, and failure to replicate the findings. While most of the studies have been focused on C-reactive protein, further efforts should investigate other inflammatory markers.
Published: 2019
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42. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the Global Burden of Disease Study 2017

Author: Gregory A Roth, Degu Abate, Kalkidan Hassen Abate, Solomon M Abay, Cristiana Abbafati, Nooshin Abbasi, Hedayat Abbastabar, Foad Abd-Allah, Jemal Abdela, Ahmed Abdelalim, Ibrahim Abdollahpour, Rizwan Suliankatchi Abdulkader, Haftom Temesgen Abebe, Molla Abebe, Zegeye Abebe, Ayenew Negesse Abejie, Semaw F Abera, Olifan Zewdie Abil, Haftom Niguse Abraha, Aklilu Roba Abrham, Laith Jamal Abu-Raddad, Manfred Mario Kokou Accrombessi, Dilaram Acharya, Abdu A Adamu, Oladimeji M Adebayo, Rufus Adesoji Adedoyin, Victor Adekanmbi, Olatunji O Adetokunboh, Beyene Meressa Adhena, Mina G Adib, Amha Admasie, Ashkan Afshin, Gina Agarwal, Kareha M Agesa, Anurag Agrawal, Sutapa Agrawal, Alireza Ahmadi, Mehdi Ahmadi, Muktar Beshir Ahmed, Sayem Ahmed, Amani Nidhal Aichour, Ibtihel Aichour, Miloud Taki Eddine Aichour, Mohammad Esmaeil Akbari, Rufus Olusola Akinyemi, Nadia Akseer, Ziyad Al-Aly, Ayman Al-Eyadhy, Rajaa M Al-Raddadi, Fares Alahdab, Khurshid Alam, Tahiya Alam, Animut Alebel, Kefyalew Addis Alene, Mehran Alijanzadeh, Reza Alizadeh-Navaei, Syed Mohamed Aljunid, Ala'a Alkerwi, François Alla, Peter Allebeck, Jordi Alonso, Khalid Altirkawi, Nelson Alvis-Guzman, Azmeraw T Amare, Leopold N Aminde, Erfan Amini, Walid Ammar, Yaw Ampem Amoako, Nahla Hamed Anber, Catalina Liliana Andrei, Sofia Androudi, Megbaru Debalkie Animut, Mina Anjomshoa, Hossein Ansari, Mustafa Geleto Ansha, Carl Abelardo T Antonio, Palwasha Anwari, Olatunde Aremu, Johan Ärnlöv, Amit Arora, Monika Arora, Al Artaman, Krishna K Aryal, Hamid Asayesh, Ephrem Tsegay Asfaw, Zerihun Ataro, Suleman Atique, Sachin R Atre, Marcel Ausloos, Euripide F G A Avokpaho, Ashish Awasthi, Beatriz Paulina Ayala Quintanilla, Yohanes Ayele, Rakesh Ayer, Peter S Azzopardi, Arefeh Babazadeh, Umar Bacha, Hamid Badali, Alaa Badawi, Ayele Geleto Bali, Katherine E Ballesteros, Maciej Banach, Kajori Banerjee, Marlena S Bannick, Joseph Adel Mattar Banoub, Miguel A Barboza, Suzanne Lyn Barker-Collo, Till Winfried Bärnighausen, Simon Barquera, Lope H Barrero, Quique Bassat, Sanjay Basu, Bernhard T Baune, Habtamu Wondifraw Baynes, Shahrzad Bazargan-Hejazi, Neeraj Bedi, Ettore Beghi, Masoud Behzadifar, Meysam Behzadifar, Yannick Béjot, Bayu Begashaw Bekele, Abate Bekele Belachew, Ezra Belay, Yihalem Abebe Belay, Michelle L Bell, Aminu K Bello, Derrick A Bennett, Isabela M Bensenor, Adam E Berman, Eduardo Bernabe, Robert S Bernstein, Gregory J Bertolacci, Mircea Beuran, Tina Beyranvand, Ashish Bhalla, Suraj Bhattarai, Soumyadeeep Bhaumik, Zulfiqar A Bhutta, Belete Biadgo, Molly H Biehl, Ali Bijani, Boris Bikbov, Ver Bilano, Nigus Bililign, Muhammad Shahdaat Bin Sayeed, Donal Bisanzio, Tuhin Biswas, Brigette F Blacker, Berrak Bora Basara, Rohan Borschmann, Cristina Bosetti, Kayvan Bozorgmehr, Oliver J Brady, Luisa C Brant, Carol Brayne, Alexandra Brazinova, Nicholas J K Breitborde, Hermann Brenner, Paul Svitil Briant, Gabrielle Britton, Traolach Brugha, Reinhard Busse, Zahid A Butt, Charlton S K H Callender, Ismael R Campos-Nonato, Julio Cesar Campuzano Rincon, Jorge Cano, Mate Car, Rosario Cárdenas, Giulia Carreras, Juan J Carrero, Austin Carter, Félix Carvalho, Carlos A Castañeda-Orjuela, Jacqueline Castillo Rivas, Chris D Castle, Clara Castro, Franz Castro, Ferrán Catalá-López, Ester Cerin, Yazan Chaiah, Jung-Chen Chang, Fiona J Charlson, Pankaj Chaturvedi, Peggy Pei-Chia Chiang, Odgerel Chimed-Ochir, Vesper Hichilombwe Chisumpa, Abdulaal Chitheer, Rajiv Chowdhury, Hanne Christensen, Devasahayam J Christopher, Sheng-Chia Chung, Flavia M Cicuttini, Liliana G Ciobanu, Massimo Cirillo, Aaron J Cohen, Leslie Trumbull Cooper, Paolo Angelo Cortesi, Monica Cortinovis, Ewerton Cousin, Benjamin C Cowie, Michael H Criqui, Elizabeth A Cromwell, Christopher Stephen Crowe, John A Crump, Matthew Cunningham, Alemneh Kabeta Daba, Abel Fekadu Dadi, Lalit Dandona, Rakhi Dandona, Anh Kim Dang, Paul I Dargan, Ahmad Daryani, Siddharth K Das, Rajat Das Gupta, José Das Neves, Tamirat Tesfaye Dasa, Aditya Prasad Dash, Adrian C Davis, Nicole Davis Weaver, Dragos Virgil Davitoiu, Kairat Davletov, Fernando Pio De La Hoz, Jan-Walter De Neve, Meaza Girma Degefa, Louisa Degenhardt, Tizta T Degfie, Selina Deiparine, Gebre Teklemariam Demoz, Balem Betsu Demtsu, Edgar Denova-Gutiérrez, Kebede Deribe, Nikolaos Dervenis, Don C Des Jarlais, Getenet Ayalew Dessie, Subhojit Dey, Samath D Dharmaratne, Daniel Dicker, Mesfin Tadese Dinberu, Eric L Ding, M Ashworth Dirac, Shirin Djalalinia, Klara Dokova, David Teye Doku, Christl A Donnelly, E Ray Dorsey, Pratik P Doshi, Dirk Douwes-Schultz, Kerrie E Doyle, Tim R Driscoll, Manisha Dubey, Eleonora Dubljanin, Eyasu Ejeta Duken, Bruce B Duncan, Andre R Duraes, Hedyeh Ebrahimi, Soheil Ebrahimpour, Dumessa Edessa, David Edvardsson, Anne Elise Eggen, Charbel El Bcheraoui, Maysaa El Sayed Zaki, Ziad El-Khatib, Hajer Elkout, Christian Lycke Ellingsen, Matthias Endres, Aman Yesuf Endries, Benjamin Er, Holly E Erskine, Babak Eshrati, Sharareh Eskandarieh, Reza Esmaeili, Alireza Esteghamati, Mahdi Fakhar, Hamed Fakhim, Mahbobeh Faramarzi, Mohammad Fareed, Farzaneh Farhadi, Carla Sofia E sá Farinha, Andre Faro, Maryam S Farvid, Farshad Farzadfar, Mohammad Hosein Farzaei, Valery L Feigin, Andrea B Feigl, Netsanet Fentahun, Seyed-Mohammad Fereshtehnejad, Eduarda Fernandes, Joao C Fernandes, Alize J Ferrari, Garumma Tolu Feyissa, Irina Filip, Samuel Finegold, Florian Fischer, Christina Fitzmaurice, Nataliya A Foigt, Kyle J Foreman, Carla Fornari, Tahvi D Frank, Takeshi Fukumoto, John E Fuller, Nancy Fullman, Thomas Fürst, João M Furtado, Neal D Futran, Silvano Gallus, Alberto L Garcia-Basteiro, Miguel A Garcia-Gordillo, William M Gardner, Abadi Kahsu Gebre, Tsegaye Tewelde Gebrehiwot, Amanuel Tesfay Gebremedhin, Bereket Gebremichael, Teklu Gebrehiwo Gebremichael, Tilayie Feto Gelano, Johanna M Geleijnse, Ricard Genova-Maleras, Yilma Chisha Dea Geramo, Peter W Gething, Kebede Embaye Gezae, Mohammad Rasoul Ghadami, Reza Ghadimi, Khalil Ghasemi Falavarjani, Maryam 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Zubair Kabir, Rajendra Kadel, Amaha Kahsay, Rizwan Kalani, Manoochehr Karami, Behzad Karami Matin, André Karch, Corine Karema, Hamidreza Karimi-Sari, Amir Kasaeian, Dessalegn H Kassa, Getachew Mullu Kassa, Tesfaye Dessale Kassa, Nicholas J Kassebaum, Srinivasa Vittal Katikireddi, Anil Kaul, Zhila Kazemi, Ali Kazemi Karyani, Dhruv Satish Kazi, Adane Teshome Kefale, Peter Njenga Keiyoro, Grant Rodgers Kemp, Andre Pascal Kengne, Andre Keren, Chandrasekharan Nair Kesavachandran, Yousef Saleh Khader, Behzad Khafaei, Morteza Abdullatif Khafaie, Alireza Khajavi, Nauman Khalid, Ibrahim A Khalil, Ejaz Ahmad Khan, Muhammad Shahzeb Khan, Muhammad Ali Khan, Young-Ho Khang, Mona M Khater, Abdullah T Khoja, Ardeshir Khosravi, Mohammad Hossein Khosravi, Jagdish Khubchandani, Aliasghar A Kiadaliri, Getiye D Kibret, Zelalem Teklemariam Kidanemariam, Daniel N Kiirithio, Daniel Kim, Young-Eun Kim, Yun Jin Kim, Ruth W Kimokoti, Yohannes Kinfu, Adnan Kisa, Katarzyna Kissimova-Skarbek, Mika Kivimäki, Ann 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Gopalakrishnan Natarajan, Nahid Neamati, Ionut Negoi, Ruxandra Irina Negoi, Subas Neupane, Charles R J Newton, Frida N Ngalesoni, Josephine W Ngunjiri, Anh Quynh Nguyen, Grant Nguyen, Ha Thu Nguyen, Huong Thanh Nguyen, Long Hoang Nguyen, Minh Nguyen, Trang Huyen Nguyen, Emma Nichols, Dina Nur Anggraini Ningrum, Yirga Legesse Nirayo, Molly R Nixon, Nomonde Nolutshungu, Shuhei Nomura, Ole F Norheim, Mehdi Noroozi, Bo Norrving, Jean Jacques Noubiap, Hamid Reza Nouri, Malihe Nourollahpour Shiadeh, Mohammad Reza Nowroozi, Peter S Nyasulu, Christopher M Odell, Richard Ofori-Asenso, Felix Akpojene Ogbo, In-Hwan Oh, Olanrewaju Oladimeji, Andrew T Olagunju, Pedro R Olivares, Helen Elizabeth Olsen, Bolajoko Olubukunola Olusanya, Jacob Olusegun Olusanya, Kanyin L Ong, Sok King Sk Ong, Eyal Oren, Heather M Orpana, Alberto Ortiz, Justin R Ortiz, Stanislav S Otstavnov, Simon Øverland, Mayowa Ojo Owolabi, Raziye Özdemir, Mahesh P A, Rosana Pacella, Smita Pakhale, Abhijit P Pakhare, Amir H Pakpour, Adrian Pana, Songhomitra Panda-Jonas, Jeyaraj Durai Pandian, Andrea Parisi, Eun-Kee Park, Charles D H Parry, Hadi Parsian, Shanti Patel, Sanghamitra Pati, George C Patton, Vishnupriya Rao Paturi, Katherine R Paulson, Alexandre Pereira, David M Pereira, Norberto Perico, Konrad Pesudovs, Max Petzold, Michael R Phillips, Frédéric B Piel, David M Pigott, Julian David Pillay, Meghdad Pirsaheb, Farhad Pishgar, Suzanne Polinder, Maarten J Postma, Akram Pourshams, Hossein Poustchi, Ashwini Pujar, Swayam Prakash, Narayan Prasad, Caroline A Purcell, Mostafa Qorbani, Hedley Quintana, D Alex Quistberg, Kirankumar Waman Rade, Amir Radfar, Anwar Rafay, Alireza Rafiei, Fakher Rahim, Kazem Rahimi, Afarin Rahimi-Movaghar, Mahfuzar Rahman, Mohammad Hifz Ur Rahman, Muhammad Aziz Rahman, Rajesh Kumar Rai, Sasa Rajsic, Usha Ram, Chhabi Lal Ranabhat, Prabhat Ranjan, Puja C Rao, David Laith Rawaf, Salman Rawaf, Christian Razo-García, K Srinath Reddy, Robert C Reiner, Marissa B Reitsma, Giuseppe Remuzzi, 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Nooshin
Subjects: Overview, Disease, Territory, Causes of death, humanities
Abstract: Global development goals increasingly rely on country-specific estimates for benchmarking a nation's progress. To meet this need, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated global, regional, national, and, for selected locations, subnational cause-specific mortality beginning in the year 1980. Here we report an update to that study, making use of newly available data and improved methods. GBD 2017 provides a comprehensive assessment of cause-specific mortality for 282 causes in 195 countries and territories from 1980 to 2017. The Lancet Publishing Group
Published: 2019

43. Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies

Author: Dorairaj Prabhakaran, Susmita Chowdhury, Francesca L. Crowe, Cristina Pellegrino Baena, Becca Feldman, Oscar H. Franco, Laura Johnson, Frank B. Hu, Clare Oliver-Williams, An Pan, Anna Vitezova, Setor K Kunutsor, Jessica C Kiefte-de-Jong, Rajiv Chowdhury, Moshe Hoshen, Hassan Khan, Epidemiology, Chowdhury, Rajiv [0000-0003-4881-5690], Oliver-Williams, Clare [0000-0002-3573-2426], and Apollo - University of Cambridge Repository
Subjects: medicine.medical_specialty, business.industry, Research, MEDLINE, Cancer, General Medicine, Vitamins, medicine.disease, Vitamin D Deficiency, vitamin D deficiency, SDG 3 - Good Health and Well-being, Risk Factors, Meta-analysis, Internal medicine, Cause of Death, Immunology, Cohort, Dietary Supplements, medicine, Vitamin D and neurology, Humans, Observational study, Vitamin D, business, Cause of death
Abstract: OBJECTIVE: To evaluate the extent to which circulating biomarker and supplements of vitamin D are associated with mortality from cardiovascular, cancer, or other conditions, under various circumstances. DESIGN: Systematic review and meta-analysis of observational studies and randomised controlled trials. DATA SOURCES: Medline, Embase, Cochrane Library, and reference lists of relevant studies to August 2013; correspondance with investigators. STUDY SELECTION: Observational cohort studies and randomised controlled trials in adults, which reported associations between vitamin D (measured as circulating 25-hydroxyvitamin D concentration or vitamin D supplement given singly) and cause specific mortality outcomes. DATA EXTRACTION: Data were extracted by two independent investigators, and a consensus was reached with involvement of a third. Study specific relative risks from 73 cohort studies (849,412 participants) and 22 randomised controlled trials (vitamin D given alone versus placebo or no treatment; 30,716 participants) were meta-analysed using random effects models and were grouped by study and population characteristics. RESULTS: In the primary prevention observational studies, comparing bottom versus top thirds of baseline circulating 25-hydroxyvitamin D distribution, pooled relative risks were 1.35 (95% confidence interval 1.13 to 1.61) for death from cardiovascular disease, 1.14 (1.01 to 1.29) for death from cancer, 1.30 (1.07 to 1.59) for non-vascular, non-cancer death, and 1.35 (1.22 to 1.49) for all cause mortality. Subgroup analyses in the observational studies indicated that risk of mortality was significantly higher in studies with lower baseline use of vitamin D supplements. In randomised controlled trials, relative risks for all cause mortality were 0.89 (0.80 to 0.99) for vitamin D3 supplementation and 1.04 (0.97 to 1.11) for vitamin D2 supplementation. The effects observed for vitamin D3 supplementation remained unchanged when grouped by various characteristics. However, for vitamin D2 supplementation, increased risks of mortality were observed in studies with lower intervention doses and shorter average intervention periods. CONCLUSIONS: Evidence from observational studies indicates inverse associations of circulating 25-hydroxyvitamin D with risks of death due to cardiovascular disease, cancer, and other causes. Supplementation with vitamin D3 significantly reduces overall mortality among older adults; however, before any widespread supplementation, further investigations will be required to establish the optimal dose and duration and whether vitamin D3 and D2 have different effects on mortality risk.
Published: 2018
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44. The role of global and regional DNA methylation and histone modifications in glycemic traits and type 2 diabetes

Author: John Troup, Abbas Dehghan, Wichor M. Bramer, Rajiv Chowdhury, Oscar H. Franco, Trudy Voortman, Kim V.E. Braun, Taulant Muka, Jana Nano, Saverio Stranges, Symen Ligthart, Chowdhury, Rajiv [0000-0003-4881-5690], Apollo - University of Cambridge Repository, Epidemiology, and Medical Informatics
Subjects: 0301 basic medicine, Blood Glucose, Male, Candidate gene, endocrine system diseases, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Medicine (miscellaneous), Type 2 diabetes, Bioinformatics, Epigenesis, Genetic, Histones, 0302 clinical medicine, Risk Factors, Insulin, Nutrition and Dietetics, biology, Acetylation, Histone, Phenotype, DNA methylation, Epigenetics, Female, Cardiology and Cardiovascular Medicine, Histone modification, 030209 endocrinology & metabolism, 03 medical and health sciences, Insulin resistance, SDG 3 - Good Health and Well-being, Diabetes mellitus, medicine, Humans, Genetic Predisposition to Disease, Genetic Association Studies, Global DNA methylation, nutritional and metabolic diseases, DNA Methylation, medicine.disease, Chromatin Assembly and Disassembly, 030104 developmental biology, Glucose, Diabetes Mellitus, Type 2, Gene Expression Regulation, biology.protein, Gene-Environment Interaction, Biomarkers
Abstract: Background: New evidence suggests the potential involvement of epigenetic mechanisms in type 2 diabetes (T2D) as a crucial interface between the effects of genetic predisposition and environmental influences.Aim: To systematically review studies investigating the association between epigenetic marks (DNA methylation and histone modifications) with T2D and glycemic traits (glucose and insulin levels, insulin resistance measured by HOMA-IR).Method and Results: Six bibliographic databases (Embase.com, Medline (Ovid), Web-of-Science, PubMed, Cochrane Central and Google Scholar) were screened until 28th August 2015. We included randomized controlled trials, cohort, case-control and cross-sectional studies in humans that examined the association between epigenetic marks (global, candidate or genome-wide methylation of DNA and histone modifications) with T2D, glucose and insulin levels and insulin metabolism.Of the initially identified 3879 references, 53 articles, based on 47 unique studies met our inclusion criteria. Overall, data were available on 10,823 participants, with a total of 3358 T2D cases. There was no consistent evidence for an association between global DNA-methylation with T2D, glucose, insulin and insulin resistance. The studies reported epigenetic regulation of several candidate genes for diabetes susceptibility in blood cells, muscle, adipose tissue and placenta to be related with T2D without any general overlap between them. Histone modifications in relation to T2D were reported only in 3 observational studies.Conclusions and relevance: Current evidence supports an association between epigenetic marks and T2D. However, overall evidence is limited, highlighting the need for further larger-scale and prospective investigations to establish whether epigenetic marks may influence the risk of developing T2D. (C) 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
Published: 2016

45. The effects of lutein on respiratory health across the life course

Author: Oscar H. Franco, Janine F. Felix, Wichor M. Bramer, Taulant Muka, Sirwan K.L. Darweesh, Myrte J. Tielemans, Anna Vitezova, Guy Brusselle, Debora Melo van Lent, Eduardo M. Moreira, Rajiv Chowdhury, Jessica C. Kiefte-de Jong, and Elisabeth T.M. Leermakers
Subjects: Adult, 0301 basic medicine, Pediatrics, medicine.medical_specialty, Lutein, Longitudinal study, Cross-sectional study, Endocrinology, Diabetes and Metabolism, Respiratory System, Respiratory Tract Diseases, Antioxidants, law.invention, 03 medical and health sciences, chemistry.chemical_compound, Randomized controlled trial, SDG 3 - Good Health and Well-being, Zeaxanthins, law, medicine, Humans, Respiratory function, Longitudinal Studies, Child, Bronchopulmonary Dysplasia, Randomized Controlled Trials as Topic, Respiratory Sounds, Asthma, 030109 nutrition & dietetics, Nutrition and Dietetics, business.industry, Infant, Newborn, Case-control study, food and beverages, medicine.disease, Carotenoids, eye diseases, Cross-Sectional Studies, chemistry, Bronchopulmonary dysplasia, Case-Control Studies, Dietary Supplements, business
Abstract: Summary Background Lutein, a fat-soluble carotenoid present in green leafy vegetables and eggs, has strong antioxidant properties and could therefore be important for respiratory health. Design We systematically reviewed the literature for articles that evaluated associations of lutein (intake, supplements or blood levels) with respiratory outcomes, published in Medline, Embase, Cochrane Central, PubMed, Web of Science and Google Scholar, up to August 2014. Results We identified one Randomized Control Trial (RCT), two longitudinal, four prospective and six cross-sectional studies. The individual studies obtained a Quality Score ranging between 3 and 9. Six studies were performed in children, which examined bronchopulmonary dysplasia (BPD), asthma and wheezing. In adults, 7 studies investigated asthma, respiratory function and respiratory mortality. The RCT found a borderline significant effect of lutein/zeaxanthin supplementation in neonates on the risk of BPD (OR 0.43 (95% CI 0.15; 1.17). No association was found between lutein intake or levels and respiratory outcomes in children. A case–control study in adults showed lower lutein levels in asthma cases. Three studies, with a prospective or longitudinal study design, in adults found a small but a significant positive association between lutein intake or levels and respiratory function. No association was found in the other two studies. In relation to respiratory mortality, one longitudinal study showed that higher lutein blood levels were associated with a decreased mortality (HR 0.77 (95% CI 0.60; 0.99), per SD increase in lutein). Conclusion The published literature suggests a possible positive association between lutein and respiratory health. However, the literature is scarce and most studies are of observational nature.
Published: 2016
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46. The role of epigenetic modifications in cardiovascular disease: A systematic review

Author: Rajiv Chowdhury, Oscar H. Franco, Eliana Portilla, Wichor M. Bramer, John Troup, Annalouise O'Connor, Fjorda Koromani, Taulant Muka, Abbas Dehghan, Epidemiology, and Erasmus MC other
Subjects: 0301 basic medicine, Male, Cardiac & Cardiovascular Systems, Luma, TYPE-2 DIABETES-MELLITUS, HEART-DISEASE, Disease, PERIPHERAL-BLOOD, Bioinformatics, 1102 Cardiovascular Medicine And Haematology, Epigenesis, Genetic, Histones, 03 medical and health sciences, LINE-1, SDG 3 - Good Health and Well-being, Alu Elements, Medicine, Humans, Genetic Predisposition to Disease, GLOBAL DNA-METHYLATION, Epigenetics, FAMILIAL HYPERCHOLESTEROLEMIA, Gene, INSULIN-RESISTANCE, Science & Technology, DNA methylation, biology, business.industry, Histone modifications, Epigenetic, Methylation, Cardiovascular disease, F2RL3, 030104 developmental biology, Histone, MYOCARDIAL-INFARCTION, Cardiovascular System & Hematology, Cardiovascular Diseases, Genetic Loci, Cardiovascular System & Cardiology, biology.protein, CORONARY-ARTERY-DISEASE, GENE PROMOTER, Female, business, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, LINE-1 METHYLATION
Abstract: © 2015 Elsevier Ireland Ltd. All rights reserved. Background Epigenetic modifications of the genome, such as DNA methylation and histone modifications, have been reported to play a role in processes underlying cardiovascular disease (CVD), including atherosclerosis, inflammation, hypertension and diabetes. Methods Eleven databases were searched for studies investigating the association between epigenetic marks (either global, site-specific or genome-wide methylation of DNA and histone modifications) and CVD. Results Of the 3459 searched references, 31 studies met our inclusion criteria (26 cross-sectional studies and 5 prospective studies). Overall, 12,648 individuals were included, with total of 4037 CVD events. The global DNA methylation assessed at long-interspersed nuclear element (LINE-1) was inversely associated with CVD, independent of established cardiovascular risk factors. Conversely, a higher degree of global DNA methylation measured at Alu repeats or by the LUMA method was associated with the presence of CVD. The studies reported epigenetic regulation of 34 metabolic genes (involved in fetal growth, glucose and lipid metabolism, inflammation, atherosclerosis and oxidative stress) in blood cells to be related with CVD. Among them, 5 loci were validated and methylation at F2RL3 was reported in two large prospective studies to predict cardiovascular disease beyond the traditional risk factors. Conclusions Current evidence supports an association between genomic DNA methylation and CVD. However, this review highlights important gaps in the existing evidences including lack of large-scale epigenetic investigations, needed to reliably identify genomic loci where DNA methylation is related to risk of CVD.
Published: 2016
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47. The effects of lutein on cardiometabolic health across the life course: a systematic review and meta-analysis

Author: Myrte J. Tielemans, Anna Vitezova, Sirwan K.L. Darweesh, Jessica C. Kiefte-de Jong, Janine F. Felix, Eduardo M. Moreira, Debora Melo van Lent, Taulant Muka, Elisabeth T.M. Leermakers, Wichor M. Bramer, Oscar H. Franco, Rajiv Chowdhury, Cristina Pellegrino Baena, Epidemiology, and Erasmus MC other
Subjects: 0301 basic medicine, medicine.medical_specialty, Lutein, antioxidant, Medicine (miscellaneous), Blood lipids, 030204 cardiovascular system & hematology, Lower risk, Antioxidants, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Insulin resistance, systematic review, Risk Factors, Internal medicine, medicine, Humans, Glucose Metabolism Disorders, Metabolic Syndrome, life course, Pregnancy, lutein, Evidence-Based Medicine, 030109 nutrition & dietetics, Nutrition and Dietetics, business.industry, Age Factors, medicine.disease, Carotenoids, Diet, Diabetes Mellitus, Type 2, chemistry, Cardiovascular Diseases, Meta-analysis, Dietary Supplements, Cohort, Metabolic syndrome, business, Biomarkers, cardiometabolic health
Abstract: Background The antioxidant lutein is suggested as being beneficial to cardiometabolic health because of its protective effect against oxidative stress, but evidence has not systematically been evaluated. Objective We aimed to evaluate systematically the effects of lutein (intake or concentrations) on cardiometabolic outcomes in different life stages. Design This is a systematic review with meta-analysis of literature published in MEDLINE, Embase, Cochrane Central, Web of Science, PubMed, and Google Scholar up to August 2014. Included were trials and cohort, case-control, and cross-sectional studies in which the association between lutein concentrations, dietary intake, or supplements and cardiometabolic outcomes was reported. Two independent investigators reviewed the articles. Results Seventy-one relevant articles were identified that included a total of 387,569 participants. Only 1 article investigated the effects of lutein during pregnancy, and 3 studied lutein in children. Furthermore, 31 longitudinal, 33 cross-sectional, and 3 intervention studies were conducted in adults. Meta-analysis showed a lower risk of coronary heart disease (pooled RR: 0.88; 95% CI: 0.80, 0.98) and stroke (pooled RR: 0.82; 95% CI: 0.72, 0.93) for the highest compared with the lowest tertile of lutein blood concentration or intake. There was no significant association with type 2 diabetes mellitus (pooled RR: 0.97; 95% CI: 0.77, 1.22), but higher lutein was associated with a lower risk of metabolic syndrome (pooled RR: 0.75; 95% CI: 0.60, 0.92) for the highest compared with the lowest tertile. The literature on risk factors for cardiometabolic diseases showed that lutein might be beneficial for atherosclerosis and inflammatory markers, but there were inconsistent associations with blood pressure, adiposity, insulin resistance, and blood lipids. Conclusions Our findings suggest that higher dietary intake and higher blood concentrations of lutein are generally associated with better cardiometabolic health. However, evidence mainly comes from observational studies in adults, whereas large-scale intervention studies and studies of lutein during pregnancy and childhood are scarce.
Published: 2016
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48. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013

Author: Yong Zhao, Hadi Danawi, Bach Xuan Tran, Gene Bukhman, Vasiliki Stathopoulou, Taavi Tillmann, Nelson Alvis-Guzman, Yongmei Li, Jerry Puthenpurakal Abraham, Sudan Prasad Neupane, Jack Caravanos, Ben Schöttker, Rafael Lozano, Damian G Hoy, Yoshihiro Kokubo, Nicholas J K Breitborde, Sergey Soshnikov, Yukito Shinohara, Randall V. Martin, Michael Brainin, Fernando Perez-Ruiz, Yingfeng Zheng, Santosh Mishra, Julio Cesar Montañez Hernandez, Michael Phillips, Belinda J. Gabbe, Hebe N. Gouda, Ziad A. Memish, Rupert R A Bourne, Guoqing Hu, Emmanuel A. Ameh, Abigail McLain, Michelle L. Bell, Christopher Margono, Marissa Iannarone, Wilkister N. Moturi, Donald H. Silberberg, Carl Abelardo T. Antonio, Nataliya Foigt, Anand Dayama, Yanping Wang, Amanda J. Mason-Jones, Bolajoko O. Olusanya, Monica S. Vavilala, Katherine B Gibney, David Tanne, Sidibe S Kany Roseline, Marcella Montico, Abhishek Singh, Sarah Derrett, Alireza Esteghamati, Seok Jun Yoon, Corine Karema, Rakhi Dandona, David M. Pereira, Kazem Rahimi, Gitanjali M. Singh, Vivekanand Jha, John Hornberger, Anne M. Riederer, Kathryn H. Jacobsen, Andrea Pedroza, Lily Alexander, Fiona M. Blyth, Tommi Vasankari, Kyle J Foreman, Rana J. Asghar, Tilahun Nigatu Haregu, Yousef Khader, Rafael Alfonso-Cristancho, Suzanne Barker-Collo, Lydia S. Atkins, Simerjot K. Jassal, Mohammad Ali Sahraian, Peter Scarborough, Hans W. Hoek, E. Ray Dorsey, Muluken Dessalegn, David C. Schwebel, Gavin Shaddick, Thomas D. Fleming, Mohammad Tavakkoli, Dorairaj Prabhakaran, Mohammad H. Forouzanfar, Christopher C. Mapoma, Jost B. Jonas, Erin C Mullany, Gene F. Kwan, Johanna M. Geleijnse, Antonio Luiz Pinho Ribeiro, Roberto Tchio Talongwa, Tolesa Bekele, Jed D. Blore, Gunn Marit Aasvang, Philimon Gona, Miguel Angel Alegretti, Babak Eshrati, Mitsuru Mukaigawara, Richard F. Gillum, Odgerel Chimed-Ochir, Ubai Alsharif, Richard C. Franklin, Felix Masiye, Richard T. Burnett, Sanjay Krishnaswami, Martin McKee, John J Huang, Lucía Cuevas-Nasu, Wagner Marcenes, Walid Ammar, Knud Juel, Joseph R. Zunt, Martha M Téllez Rojo, Mamta Swaroop, Noela M Prasad, Azmeraw T. Amare, Tim Driscoll, Michael Kravchenko, Heresh Amini, Amir Sapkota, Theo Vos, Charlotte Watts, Dennis Odai Laryea, D. Alex Quistberg, Justin Beardsley, Cheng Huang, Adnan M. Durrani, Sarah V Thackway, Rita Van Dingenen, Manami Inoue, Martha Híjar, Honglei Chen, Amany H. Refaat, Yichong Li, Vineet K. Chadha, Wenzhi Wang, Louisa Degenhardt, Kingsley N. Ukwaja, Nayu Ikeda, James D. Wilkinson, Linh N Bui, Maria Hagströmer, Gonghuan Yang, Ann Kristin Knudsen, David J. Margolis, Soewarta Kosen, Hans Kromhout, Atsushi Goto, Man Mohan Mehndiratta, Thomas N. Williams, Michael Soljak, Yun Jin Kim, Hideaki Toyoshima, Jeyaraj D Pandian, Borja del Pozo-Cruz, Soufiane Boufous, Ivy Shiue, Anders Larsson, Guilherme V. Polanczyk, John Powles, Yara A. Halasa, Robin Room, Ratilal Lalloo, Carolina Batis Ruvalcaba, Panniyammakal Jeemon, Elisabete Weiderpass, Jürgen Rehm, Ejaz Ahmad Khan, Alicia Aleman, Zacharie Tsala Dimbuene, Elena Alvarez, Rachelle Buchbinder, Randah R. Hamadeh, Bryan Hubbell, Sadaf G. Sepanlou, Farhad Islami, Costas A. Christophi, Heidi Stöckl, Ismael R. Campos-Nonato, Nigel Bruce, Edward J Mills, Samuel A L Perry, Taavi Lai, Baffour Awuah, Mete Saylan, Karen J. Courville, Arindam Basu, Vanessa De la Cruz-Góngora, Teresita González de Cosío, Naohiro Yonemoto, Frida Namnyak Ngalesoni, Muluken Azage Yenesew, Atte Meretoja, Michael Brauer, Cyrus Cooper, Giorgia Giussani, Valentina S. Arsic Arsenijevic, Vasiliy Victorovich Vlassov, André Karch, Leilei Duan, Matthew M Coates, Omid Ameli, Gelin Xu, Matthias Endres, Ganesan Karthikeyan, Ione Jayce Ceola Schneider, Mohamed Hsairi, Palwasha Anwari, Mazin J. Al Khabouri, Dariush Mozaffarian, Juan R. Sanabria, Pablo M. Lavados, Sumeet S. Chugh, Johan Ärnlöv, Ivo Rakovac, Maurice Giroud, Haidong Kan, Ibrahim Abdelmageem Mohamed Ginawi, José Luis Texcalac-Sangrador, Luigi Naldi, Erica Leigh Slepak, Deena Alasfoor, James E. Saunders, Richard Matzopoulos, Talal Bakfalouni, Stein Emil Vollset, Andrea Werdecker, Lennert J. Veerman, Lorenzo Monasta, Henrica A. F. M. Jansen, Reyna A Gutiérrez, Brittany Wurtz, Luz Maria Sanchez, Lijing L. Yan, M. Patrice Lindsay, Michele Meltzer, Sanjay Basu, Steven van de Vijver, Alaa Badawi, Thomas Claßen, Young-Ho Khang, Brett M. Kissela, Jun Zhu, In-Hwan Oh, Fiona J Charlson, Maria Cecilia Bahit, Dinorah González-Castell, Rosario Cárdenas, Dan Poenaru, Sayed Saidul Alam, Mitchell T. Wallin, Harish Chander Gugnani, James Leigh, Ferrán Catalá-López, Lidia Morawska, Jim van Os, Stephanie J. London, Kaire Innos, Isabelle Romieu, Fiorella Cavalleri, Adrian Davis, Hwee Pin Phua, Chakib Nejjari, Héctor Gómez Dantés, Boris I. Pavlin, Karen Sliwa, Lynne Gaffikin, Constance D. Pond, Michael F. MacIntyre, Blake Thomson, Norberto Perico, Ronny Westerman, Samantha M. Colquhoun, Michael H. Criqui, Ana Maria Nogales Vasconcelos, Wubegzier Mekonnen, Bulat Idrisov, Ana Basto-Abreu, Andrew G. M. Bulloch, Jasvinder A. Singh, Vinod K. Paul, Emin Murat Tuzcu, Svetlana Popova, Hmwe H Kyu, Richard L. Guerrant, Mohammed I. Albittar, Srikanth Mangalam, Steven E. Lipshultz, Lela Sturua, Semaw Ferede Abera, Eduardo Bernabé, George D. Thurston, Bruno F. Sunguya, Tiffany Ku, Alejandra G. Contreras, Abdullah Sulieman Terkawi, Charles Atkinson, Ashkan Afshin, Heidi J. Larson, Abdullatif Husseini, Jose C. Adsuar, Reza Assadi, Ademola Lukman Adelekan, Joshua A. Salomon, Yousef M. Elshrek, Gokalp Kadri Yentur, Devina Nand, Narayanaswamy Venketasubramanian, Graça Maria Ferreira De Lima, Maheswar Satpathy, Fotis Topouzis, Traolach S. Brugha, Hywel C Williams, Coen H. Van Gool, Andrew H. Kemp, Awoke Misganaw, Amado D Quezada, Norito Kawakami, Bert Brunekreef, Peter Burney, Tati S. Warouw, Jongmin Lee, Inga Dora Sigfusdottir, Marcel Tanner, Solveig A. Cunningham, Benjamin O. Anderson, Tariku Jibat Beyene, Lars Barregard, Xia Wan, Giuseppe Remuzzi, Bernadette Thomas, Lilia S Pedraza, Massimo Cirillo, Alina Rodriguez, Ricky Leung, Farshad Pourmalek, K. Srinath Reddy, Charles D.A. Wolfe, Ulrich O Mueller, Neeraj Bedi, Al Artaman, Lucia Hernandez, Itamar S. Santos, C. Arden Pope, Norlinah Mohamed Ibrahim, Carlo Irwin A. Panelo, Selen Begüm Uzun, Miltiadis K. Tsilimbaris, Anwar Rafay, Daniel Dicker, Melvin Barrientos Marzan, Sajjad Ur Rahman, Mohammed O. Basulaiman, Edgar P. Simard, Mohammad T Mashal, Maysaa El Sayed Zaki, Shiwei Liu, Don C. Des Jarlais, Bo Norrving, Salvador Villalpando, Miia Kivipelto, Yang Liu, Carolina Maria Teixeira, Catalina Medina, Sudha Jayaraman, Josep Maria Haro, Diego De Leo, Angel J Paternina Caicedo, Abigail C. McKay, Eric L. Ding, Mukesh Dherani, Ljiljana Pejin Stokic, Vinay Nangia, Sukanta Saha, Juan Liang, Elisabeth Cardis, Zourkaleini Younoussi, José R Nogueira, Braden Te Ao, Vasco Manuel Pedro Machado, Lionel Racapé, Ting Wu Chuang, Shahab Khatibzadeh, E Filipa de Castro, Barthelemy Kuate Defo, Ulises Trujillo, Alan D. Lopez, Soraya Seedat, Lope H Barrero, Linhong Wang, Daniel Pope, Alexandra Brazinova, Faris Lami, Valentina Colistro, G Anil Kumar, Derek F J Fay, Haidong Wang, Hwashin H. Shin, Raimundas Lunevicius, Suzanne Polinder, Dietrich Plass, David Rojas-Rueda, Stephen S Lim, Tania G Sánchez-Pimienta, K.M. Venkat Narayan, Yuantao Hao, Jung-Chen Chang, Corina Benjet, Seyed-Mohammad Fereshtehnejad, Luciano A. Sposato, Stan Biryukov, Kunihiro Matsushita, Beth E. Ebel, Cleusa P. Ferri, Soumya Swaminathan, K. Ryan Wessells, Gustavo Velasquez-Melendez, Leslie T. Cooper, David O. Carpenter, Nancy Lopez, Bryan L. Sykes, Sandra Nolte, Murray B. Stein, Paul N. Jensen, Fabiola Mejía-Rodríguez, Xiaonong Zou, Bradford D. Gessner, Dhruv S. Kazi, Dragos Virgil Davitoiu, Alejandra Jáuregui, Pouria Heydarpour, Megan Bohensky, Harvey Whiteford, Berrak Bora Basara, Zhengming Chen, Gregory R. Wagner, Paul I. Dargan, Hermann Brenner, Nima Hafezi-Nejad, John Nelson Opio, Scott Weichenthal, Deborah Salvo, Jun She, Tea Lallukka, Carolyn C. Gotay, Stephen G. Waller, Christian Kieling, Shivanthi Balalla, Valery L. Feigin, Qing Lan, Matias Trillini, Adam D M Briggs, Sungroul Kim, Niveen M E Abu-Rmeileh, Renata Micha, Sergey Petrovich Ermakov, Ole Frithjof Norheim, Zulfiqar A Bhutta, Paul S. F. Yip, Grant Nguyen, Ralph L. Sacco, Biju Abraham, Ken Takahashi, Jixiang Ma, Peter A. Meaney, Ayse Abbasoglu Ozgoren, Kimberly Cooperrider, M Rifat Kose, Shams Eldin Ali Hassan Khalifa, Rasmus Havmoeller, Alize J. Ferrari, Kebede Deribe, Nadim E. Karam, George A. Mensah, Bongani M. Mayosi, Konrad Pesudovs, Joanna Moschandreas, Ziad Nahas, James Damsere-Derry, Nsanzimana Sabin, Tonatiuh Barrientos-Gutiérrez, Ying Jiang, Andre Pascal Kengne, Peter Allebeck, Jonas Minet Kinge, Shankuan Zhu, Guy B. Marks, Daniel C Casey, Marco A Avila, Anna Roca, Lalit Dandona, Ami R. Moore, Adansi A. Amankwaa, David Gunnell, Andre Keren, Yohannes Adama Melaku, Nhung T Nguyen, Anthony D. Woolf, Mayuree Rao, Peter J. Allen, Christina Papachristou, Karzan Abdulmuhsin Mohammad, Ravi Kumar Balu, Marie Ng, Marcello Tonelli, Maziar Moradi-Lakeh, Maigeng Zhou, Emmanuela Gakidou, Mohammed K. Ali, Amanda W Pain, Dan J. Stein, Kawkab Shishani, Fortuné Gbètoho Gankpé, Howard J. Hoffman, James Scott, Nadine Steckling, Samia Alhabib, Deborah Jarvis, Kara Estep, Arsène Kouablan Adou, Ricardo Orozco, Holly Hagan, K. C. Astha, Reza Malekzadeh, Klara Dokova, Aliya Naheed, Ernst J. Kuipers, Valeria Caso, Derrick A Bennett, Andrea B. Feigl, Uche S. Uchendu, Holly E. Erskine, Shireen Sindi, Arjun Lakshmana Balaji, Francesco Saverio Violante, Monika Sawhney, Alejandra Cantoral, Ketevan Goginashvili, Raghib Ali, Fan Jiang, Robert G. Weintraub, Homie Razavi, Myriam Tobollik, Howard Hu, Emerito Jose A. Faraon, Irma Khonelidze, Patricia M. Riccio, Eun-Kee Park, Julio Cesar Campuzano, Ibrahim Abubakar, Jürgen C Schmidt, Konstantinos Stroumpoulis, Aref A. Bin Abdulhak, Graeme J. Hankey, Natan M. Bornstein, Mouhanad Hammami, Lee Richardson, Rintaro Mori, Alanur Çavlin, Ruth W Kimokoti, Samir Soneji, Mark J. Nieuwenhuijsen, John Q. Wong, Joseph Frostad, Tom Achoki, Rahman Shiri, Ashish Bhalla, Kurt Straif, Simon I. Hay, Scott B. Patten, Kalpana Balakrishnan, Awoke Misganaw Temesgen, Chandrashekhar T Sreeramareddy, Ryan M Barber, Rosana E. Norman, JianLi Wang, Siyi Shangguan, Luke Nyakarahuka, Kovin Naidoo, Charles D. H. Parry, Mercedes Colomar, H. Ross Anderson, Carlos Magis-Rodriguez, Joan M. Nolla, Muhammad Imran Nisar, Karen Devries, Andrew L. Thorne-Lyman, Denis Nash, Marape Marape, Rajiv Chowdhury, Dima M. Qato, Luca Ronfani, Nobhojit Roy, Daniel Kim, Yuichiro Yano, Luke D. Knibbs, Margaret Robinson, Hilda L Harb, Rogelio Pérez-Padilla, Janet L Leasher, Jonathan L. Wright, Peter Brooks, Cristiana Abbafati, Belinda K Lloyd, Victor Aboyans, Nikhil Tandon, Charles R. Newton, Simón Barquera, Ted R. Miller, Kinnari S. Murthy, Habib Benzian, Glen Mola, Paulo A. Lotufo, Burcu Kucuk Bicer, Peggy Pei-Chia Chiang, Alexander Kraemer, Solomon Meseret Woldeyohannes, Saman Fahimi, Lesley Rushton, Kim Moesgaard Iburg, Vafa Rahimi-Movaghar, Logan Sandar, Bruce Neal, Teresa Shamah Levy, Karen M. Tabb, Jeffrey A. Towbin, Christopher J L Murray, Ramesh Sahathevan, Aaron Cohen, Chanda Kulkarni, Van C. Lansingh, François Alla, Tasara T. Mazorodze, Murugesan Raju, Saeid Shahraz, Uchechukwu K.A. Sampson, Rajeev Gupta, Neil Pearce, Mustafa Z. Younis, Veena S. Kulkarni, Francisco A García-Guerra, Amanda G. Thrift, Stefan Ma, Samaya Ismayilova, Evariste Gasana, Amitava Banerjee, Aslam Pervaiz, Emilie Agardh, Abraham D. Flaxman, Farshad Farzadfar, Peter W. Gething, Ileana Heredia-Pi, Boris Bikbov, Wanqing Chen, Saad B. Omer, Ruben Castro, Neeraj Bhala, Sara Sheikhbahaei, Hilton Lam, Urbano Fra Paleo, Lidia Sanchez-Riera, Alicia Elena Beatriz Lawrynowicz, Kristen Delwiche, Richard G. Ellenbogen, Max Petzold, Yuri Y Varakin, Guilherme Borges, Guohong Jiang, Francis Guillemin, Kyle R. Heuton, Yohannes Kinfu, Victoria F Bachman, Joseph A Wagner, Carlos A Castañeda-Orjuela, Leonardo Trasande, Abbas Ali Mahdi, Josef Coresh, Chuanhua Yu, Kenji Shibuya, Berrin Serdar, Laetitia Huiart, Xiaofeng Liang, Jean de Dieu Ngirabega, Takayoshi Ohkubo, Natalie Stephens, Francis Apolinary Mhimbira, Jefferson Traebert, Amiran Gamkrelidze, Kjetil Søreide, Samath D Dharmaratne, Robert P. Dellavalle, George Mugambage Ruhago, Lakshmi Vijayakumar, Joannie Lortet-Tieulent, Dipan Bose, Tania C Aburto, Saleem M Rana, Miriam Levi, Mohammad Taghi Hedayati, Rodolfo S Pagcatipunan, Ron T. Gansevoort, H. D. Hosgood, Michael Burch, Mohsen Naghavi, Vegard Skirbekk, Ayfer Pekericli, Walter Mendoza, Pengpeng Ye, Gabrielle deVeber, Ali H. Mokdad, David M. Broday, Koranteng Adofo, Zewdie Aderaw Alemu, Shifalika Goenka, Carrie Beth Peterson, Nicolas J. C. Stapelberg, Edson Serván-Mori, Anil Kaul, Foad Abd-Allah, Marek Majdan, Rahul Gupta, Giancarlo Logroscino, Kardiyoloji, Peterson, Carrie B., Laboratoire de Physique des Solides (LPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Wisconsin Division of Public Health, Laboratoire de psychologie sociale et de psychologie cognitive (LAPSCO), Centre National de la Recherche Scientifique (CNRS)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Erosion torrentielle neige et avalanches (UR ETGR (ETNA)), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), London South Bank University, Metropolitan Police Service, Hong Kong Baptist University (HKBU), Institut für Informatik [München/Munich] (LMU), Ludwig-Maximilians-Universität München (LMU), Neuroépidémiologie Tropicale (NET), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Chirurgie Thoracique et Vasculaire - Médecine vasculaire [CHU Limoges], CHU Limoges, Insight Centre for Data Analytics [Galway] (INSIGHT), National University of Ireland [Galway] (NUI Galway), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale (INSERM), Karolinska Institute, karolinska institute, Department of Molecular Biosciences, Department of Molecular Biosciences [Oslo], Faculty of Mathematics and Natural Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Mathematics and Natural Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Centro de Estudios Avanzados en Zonas Aridas (CEAZA), Ecole Polytechnique Fédérale de Lausanne (EPFL), Regional Genetic Service, St Mary's Hospital, Manchester, Laboratoire d'Ingénierie des Matériaux (LIM), Centre National de la Recherche Scientifique (CNRS), Computer Science Department [Bristol], University of Bristol [Bristol], Universität Mannheim [Mannheim], Lawrence Berkeley National Laboratory [Berkeley] (LBNL), Samsung Research &Development Institute India - Bangalore (Groupe Samsung) (SRI-B), Computational Science and Engineering Department [Daresbury] (STFC), Science & Technologie Facilities Council, Multimedia Research Center (MRC), University of Alberta, Division of Biostatistics (Biostat - MINNEAPOLIS), University of Minnesota [Twin Cities], University of Minnesota System-University of Minnesota System, University of Southampton, Imperial College London, Neurology Department, Ichilov Medical Center, Interactions, transferts, ruptures artistiques et culturels - EA 6301 (InTRu), Université de Tours, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], Risk Assessment Sciences Institute, Utrecht University [Utrecht], Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Respiratory Epidemiology and Public Health, Imperial College London-Royal Brompton Hospital-National Heart and Lung Institute [UK], CIBER de Epidemiología y Salud Pública (CIBERESP), STAR laboratory, Stanford University [Stanford], Unité de recherche Virologie et Immunologie Moléculaires (VIM), Institut National de la Recherche Agronomique (INRA), Tennent Institute of Ophthalmology, National University of Singapore (NUS), Centre de Robotique (CAOR), MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Multidisciplinary Nanotechnology Centre, Swansea University, Cyprus International Institute for the Environment and Public Health, Harvard School of Public Health, Genomics Research Center, Academia Sinica, Neuro Rehab Services LLP [New Delhi], Department of Signal Theory and Communications (TSC), Univ. Politec. de Catalunya, King‘s College London, Dept. Mat. Engn. De Ma, Sao Carlos, Fed. Univ. Sao Carlos UFSCar, RESPEC (RESPEC), RESPEC, Advanced Laboratories on Embedded Systems [Roma] (ALES), Department of Biology [Miami], University of Miami [Coral Gables], Health Care, Minister Of Labour-Ministry of Labor, Health and Social Affairs, Department of Nephrology, University Medical Center, University of Groningen, Division of Human Nutrition, Wageningen University and Research Centre [Wageningen] (WUR), Spatial Ecology and Epidemiology Group, University of Oxford [Oxford], College of Medicine, University of Hail, Saudi Arabia, Laboratory of Neurologic Diseases, Mario Negri Institute, Milan, Department of Civil Engineering [Hamirpur], National Institute of Technology [Hamirpur], GEMMA — Environmental Engineering and Microbiology Research Group, Department of Hydraulic, Maritime and Environmental Engineering, Universitat Politècnica de Catalunya [Barcelona] (UPC), Department of Biosciences and Nutrition, Karolinska Institutet [Stockholm], Institut National de Recherche et d'Analyse Physico-Chimique (INRAP), Institut National de Recherche et d'Analyse Physico-chimique (Ariana, Tunisie) (INRAP), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences [Tehran] (SBUMS), Shahid Beheshti University-Shahid Beheshti University, Center for Applied Medical Research (CIMA), University of Tehran, Secretariat of the Pacific Community, Public Health Division, Sociétés, Acteurs, Gouvernement en Europe (SAGE), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), College of Precision Instrument and Optoelectronics Engineering, Tianjin University, George Washington University (GW), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universiteit Gent [Ghent], Washington State University (WSU), Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Institut de recherche en informatique de Toulouse (IRIT), Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, School of Computer Science - China University of Geosciences (China University of Geosciences (East Area)), Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Université Catholique de Louvain (UCL), Fachbereich Physik [Berlin], Freie Universität Berlin, Div Cyclotron & Radiopharmaceut Sci (DRDO, INMAS), Univ New Delhi, School of Physics and Astronomy, University of St Andrews [Scotland], University of Cape Town, Department of Neuroscience, Department of Computer Science and Engineering [Daejeon] (Chungnam National University), Lawrence University, Gastroenterology & Hepatology, Tata Research Development and Design Center (TRDDC), TCS Innovation Labs, University of Helsinki, Google Inc [Mountain View], Research at Google, Swedish Defense Research Agency (FOI), Servicio de Neurologia (SANTIAGO - Neurologie), Universidad del Desarrollo, Novartis Pharmaceutical Corporation, Laboratoire de glaciologie et géophysique de l'environnement (LGGE), Observatoire des Sciences de l'Univers de Grenoble [1985-2015] (OSUG [1985-2015]), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Department of Mechanical and Automation Engineering (CAD Laboratory), The Chinese University of Hong Kong [Hong Kong], Università degli studi di Bari, Department of Health and Human Services, National Institutes of Health [Bethesda] (NIH), Centre d'études et de recherche en informatique et communications (CEDRIC), Ecole Nationale Supérieure d'Informatique pour l'Industrie et l'Entreprise (ENSIIE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Heuristique et Diagnostic des Systèmes Complexes [Compiègne] (Heudiasyc), Université de Technologie de Compiègne (UTC)-Centre National de la Recherche Scientifique (CNRS), College of Information and Electrical Engineering [Beijing] (CIEE), China Agricultural University (CAU), Thales Research and Technology [Palaiseau], THALES, Department of Rheumatology and Connective Tissue Diseases, Medical University of Lublin, Barts and The London School of Medicine and Dentistry, Queen Mary University of London (QMUL), Centre d'économie de la Sorbonne (CES), Université Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS), Paris School of Economics (PSE), École supérieure du professorat et de l'éducation - Académie de Grenoble [2013-2019] (ESPE Grenoble [2013-2019]), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Department of Mathematics, University of Iowa [Iowa City], College of Medicine, Alfaisal University, Saudi Ministry of Health, Institut national des recherches agricoles du Bénin, Centre de Recherches agricoles du Sud, Departments of Epidemiology and Nutrition, Unit of Human Nutrition, Agricultural University of Athens, Department of Animal Science, Pennsylvania State University (Penn State), Penn State System-Penn State System, University of Virginia, University of Virginia [Charlottesville], Epidemiology and Biostatistics Unit, Institute for Maternal and Child Health - IRCCS ‘‘Burlo Garofolo', Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), Division of Cardiovascular Medicine and Channing Division of Network Medicine, Brigham and Women's Hospital [Boston], American University of Beirut [Beyrouth] (AUB), Department of Chemistry, Scientific Computing Research Unit, Department of dermatology, Milano University-Azienda Ospedaleria Ospedali Riuniti di Bergamo, Mailman School of Public Health, Columbia University [New York], The Georges Institute for International Health, The University of Sydney, Department of epidemiology and Public Health, Faculty of Medicine, Département Optique (OPT), Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT), Laboratoire des signaux et systèmes (L2S), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Universitat Pompeu Fabra [Barcelona], Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona]-Catalunya ministerio de salud, Nutriments Lipidiques et Prévention des Maladies Métaboliques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université de la Méditerranée - Aix-Marseille 2, Department of Neurology Lunds University Hospital Lund, Unit of Functional Bionanomaterials, School of Biosciences, University of Birmingham [Birmingham], Electrical Engineering and Computer Science Department - Case Western Reserve University, Case Western Reserve University [Cleveland], World Health Organization, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Nordic School of Public Health, The James Hutton Institute, Horia Hulubei National Institute for Physics and Nuclear Engineering, Department of Pediatrics, University of Washington [Seattle], Institute of Public Health, Department of Physics, Clarendon Laboratory, Center for TeleInFrastruktur (CTIF), Aalborg University [Denmark] (AAU), Physikalisches Institut [Freiburg], Albert-Ludwigs-Universität Freiburg, Savoirs, Textes, Langage (STL) - UMR 8163 (STL), Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Dept.of Computer Science, Indian Institute of Technology Madras (IIT Madras), Istituto Mario Negri Bergamo, Centro Ricerche e Trapianti Villa Camozzi, Universidade Estadual Paulista Júlio de Mesquita Filho [São José do Rio Preto] (UNESP), Laboratoire de Génie Informatique et Ingénierie de Production (LGI2P), IMT - MINES ALES (IMT - MINES ALES), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Institut geològic de Catalunya (IGC), Institut Geològic de Catalunya-IGC, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physiologie et Génomique des Poissons (LPGP), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Recherche Agronomique (INRA), Politecnico di Milano [Milan] (POLIMI), Symantec, University of Oviedo, European Microsoft Innovation Center (EMIC), Microsoft Corporation [Redmond, Wash.], Technion - Israel Institute of Technology [Haifa], Laboratoire de Mécanique, Physique et Géosciences (LMPG), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU), Department of Physics, Cavendish Laboratory, University of Cambridge [UK] (CAM), Laboratoire de Probabilités et Modèles Aléatoires (LPMA), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Departments of Applied Physics [New Haven], Yale University [New Haven], Center for Mathematical Modeling (CMM), Department of Global Health and Development, London School of Hygiene and Tropical Medicine (LSHTM), University of Occupational and Environmental Health [Kitakyushu] (UEOH), Department of Computer Science and Engineering [New Delhi], Indian Institute of Technology Delhi (IIT Delhi), Institut de Recherche sur les Phénomènes Hors Equilibre (IRPHE), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), GlaxoSmithKline, Imperial College London-Clinical Imaging Center, Universidade Federal de Pernambuco [Recife] (UFPE), Maclean Building, Benson Lane, Crowmarsh Gifford, Centre for Ecology and Hydrology, Nanoscience Institute (NEST), Dipartimento di Fisica, Università di Pisa, Aristotle University of Thessaloniki, Laboratory Of Immune Cell Biology (LICB), JRC Institute for Environment and Sustainability (IES), European Commission - Joint Research Centre [Ispra] (JRC), Institute of Human Genetics, Rheinische Friedrich-Wilhelms-Universität Bonn, Laboratorio Nacional de Computação Cientifica [Rio de Janeiro] (LNCC / MCT), Occupational Health Unit, Bologna University Hospital-Sant'Orsola-Malpighi Polyclinic, Royal Institute of Technology [Stockholm] (KTH ), NICTA [Eveleigh], National ICT Australia [Sydney] (NICTA), Division of Solid Mechanics, Lund University [Lund], University of Calgary, BioWare Corp, Manchester Academic Health Sciences Centre, Institut d'Histoire et de Philosophie des Sciences et des Techniques (IHPST), Université Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS)-Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Ghent University [Belgium] (UGENT), Imaging Sciences and Biomedical Engineering Division [London], Guy's and St Thomas' Hospital [London]-King‘s College London, Children’s Hospital of Philadelphia (CHOP ), Perelman School of Medicine, University of Pennsylvania [Philadelphia], Laboratoire de recherche en Hydrodynamique, Énergétique et Environnement Atmosphérique (LHEEA), École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Génie Civil et Mécanique (GeM), Université de Nantes - Faculté des Sciences et des Techniques, Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Department of Physiology, Augusta University - Medical College of Georgia, University System of Georgia (USG)-University System of Georgia (USG), Neurorestoration Group, Wolfson Centre for Age-related Diseases-King‘s College London, Electronic Navigation Research Institute (ENRI), Ministry of Land, Infrastructure, Transport and Tourism, Department of Computer Science [KAIST] (CS), Korea Advanced Institute of Science and Technology (KAIST), Centre for Undergraduate Studies, University of the Punjab, Siemens Corporate Research, Siemens AG [Munich], University of Massachusetts [Boston] (UMass Boston), University of Massachusetts System (UMASS), Department of Materials Science, Sichuan University [Chengdu] (SCU), Natl Engn Res Ctr Vegetables, Key Lab Biol & Genet Improvement Hort Crops N Chi, Beijing Acad Agr & Forestry Sci, University Hospital Puerta de Hierro, Madrid, Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), MINES ParisTech - École nationale supérieure des mines de Paris-PSL Research University (PSL), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Shahid Beheshti University of Medical Sciences, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), MOLTECH-ANJOU (MOLTECH-ANJOU), Université d'Angers (UA)-Centre National de la Recherche Scientifique (CNRS), Universidad de Santiago de Chile [Santiago] (USACH)-Universidad del Desarrollo, Observatoire des Sciences de l'Univers de Grenoble (OSUG), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), École supérieure du professorat et de l'éducation - Académie de Grenoble (ESPE Grenoble), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Grenoble Alpes (UGA), California Institute of Technology (CALTECH)-NASA, Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-Université Paris-Sud - Paris 11 (UP11), Université de la Méditerranée - Aix-Marseille 2-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universidad de Santiago de Chile [Santiago] (USACH), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris), King‘s College London-Wolfson Centre for Age-related Diseases, Sichuan University, Universitat de Barcelona, Interne Geneeskunde, Medische Sociologie, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), Psychiatrie & Neuropsychologie, CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut Mines-Télécom [Paris] (IMT)-Télécom Bretagne-Université européenne de Bretagne - European University of Brittany (UEB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), RS: MHeNs - R2 - Mental Health, Laboratoire de Physique des Solides ( LPS ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de psychologie sociale et de psychologie cognitive ( LAPSCO ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Centre National de la Recherche Scientifique ( CNRS ), Erosion torrentielle neige et avalanches ( UR ETGR ), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture ( IRSTEA ), Hong Kong Baptist University ( HKBU ), Institut für Informatik [München/Munich] ( LMU ), Ludwig-Maximilians-Universität München, Neuroépidémiologie Tropicale ( NET ), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST ), Université de Limoges ( UNILIM ) -Université de Limoges ( UNILIM ), Insight Centre for Data Analytics (National University of Ireland Galway (NUIG)) ( INSIGHT ), Maladies chroniques, santé perçue, et processus d'adaptation ( APEMAC ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale ( INSERM ), University of Oslo ( UiO ) -University of Oslo ( UiO ), Centro de Estudios Avanzados en Zonas Aridas ( CEAZA ), Ecole Polytechnique Fédérale de Lausanne ( EPFL ), Laboratoire d'Ingénierie des Matériaux ( LIM ), Centre National de la Recherche Scientifique ( CNRS ), Lawrence Berkeley National Laboratory [Berkeley] ( LBNL ), Samsung Research &Development Institute India - Bangalore (Groupe Samsung) ( SRI-B ), Computational Science and Engineering Department [Daresbury] ( STFC ), Multimedia Research Center ( MRC ), University of Alberta [Edmonton], Division of Biostatistics ( Biostat - MINNEAPOLIS ), University of Minnesota [Minneapolis], University of Southampton [Southampton], Interactions, transferts, ruptures artistiques et culturels - EA 6301 ( InTRu ), Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), University Medical Center Utrecht, Biologie Fonctionnelle et Adaptative ( BFA ), Imperial College London-Royal Brompton Hospital-National Heart and Lung Institute, Unité de recherche Virologie et Immunologie Moléculaires ( VIM ), Institut National de la Recherche Agronomique ( INRA ), National University of Singapore ( NUS ), Centre de Robotique ( CAOR ), MINES ParisTech - École nationale supérieure des mines de Paris-PSL Research University ( PSL ), Department of Signal Theory and Communications ( TSC ), RESPEC ( RESPEC ), Advanced Laboratories on Embedded Systems [Roma] ( ALES ), Wageningen University and Research Centre [Wageningen] ( WUR ), Universitat Politècnica de Catalunya [Barcelona] ( UPC ), Institut National de Recherche et d'Analyse Physico-Chimique ( INRAP ), Institut National de Recherche et d'Analyse Physico-chimique (INRAP-Tunisie), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) ( FEMTO-ST ), Université de Franche-Comté ( UFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Supérieure de Mécanique et des Microtechniques ( ENSMM ) -Université de Technologie de Belfort-Montbeliard ( UTBM ), Tehran University, Sociétés, Acteurs, Gouvernement en Europe ( SAGE ), Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale ( SESSTIM - U912 INSERM - AMU - IRD ), Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Washington State University ( WSU ), Laboratoire de Physique de l'ENS Lyon ( Phys-ENS ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Institut des Sciences Chimiques de Rennes ( ISCR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Ecole Nationale Supérieure de Chimie de Rennes-Institut National des Sciences Appliquées ( INSA ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de recherche en informatique de Toulouse ( IRIT ), Institut National Polytechnique [Toulouse] ( INP ) -Université Toulouse 1 Capitole ( UT1 ) -Université Toulouse - Jean Jaurès ( UT2J ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche en Automatique de Nancy ( CRAN ), Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), Université Catholique de Louvain ( UCL ), Freie Universität Berlin [Berlin], Div Cyclotron & Radiopharmaceut Sci ( DRDO, INMAS ), Institut de Physique Nucléaire d'Orsay ( IPNO ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ), Tata Research Development and Design Center ( TRDDC ), Laboratoire MOLTECH-Anjou [Angers] ( MOLTECH ANJOU ), Université d'Angers ( UA ) -Centre National de la Recherche Scientifique ( CNRS ), University of Helsinki [Helsinki], Swedish Defense Research Agency ( FOI ), Servicio de Neurologia ( SANTIAGO - Neurologie ), Universidad de Santiago de Chile [Santiago] ( USACH ) -Universidad del Desarrollo, Novartis Pharmaceutical Corp., East Hanover NJ 07936, USA, Laboratoire de glaciologie et géophysique de l'environnement ( LGGE ), Observatoire des Sciences de l'Univers de Grenoble ( OSUG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Mechanical and Automation Engineering ( CAD Laboratory ), National Institutes of Health ( NIH ), Centre d'étude et de recherche en informatique et communications ( CEDRIC ), Ecole Nationale Supérieure d'Informatique pour l'Industrie et l'Entreprise ( ENSIIE ) -Conservatoire National des Arts et Métiers [CNAM] ( CNAM ), Heuristique et Diagnostic des Systèmes Complexes [Compiègne] ( Heudiasyc ), Université de Technologie de Compiègne ( UTC ) -Centre National de la Recherche Scientifique ( CNRS ), College of Information and Electrical Engineering [Beijing] ( CIEE ), China Agricultural University ( CAU ), Queen Mary University of London ( QMUL ), Centre d'économie de la Sorbonne ( CES ), Université Panthéon-Sorbonne ( UP1 ) -Centre National de la Recherche Scientifique ( CNRS ), Paris School of Economics ( PSE ), École supérieure du professorat et de l'éducation - Académie de Grenoble ( ESPE Grenoble ), Université Savoie Mont Blanc ( USMB [Université de Savoie] [Université de Chambéry] ) -Université Grenoble Alpes ( UGA ), PennState University [Pennsylvania] ( PSU ), Jet Propulsion Laboratory ( JPL ), NASA-California Institute of Technology ( CALTECH ), American University of Beirut [Beyrouth], The University of Sydney [Sydney], Département Optique ( OPT ), Université européenne de Bretagne ( UEB ) -Télécom Bretagne-Institut Mines-Télécom [Paris], Laboratoire des signaux et systèmes ( L2S ), Université Paris-Sud - Paris 11 ( UP11 ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Center for Research in Environmental Epidemiology ( CREAL ), Université de la Méditerranée - Aix-Marseille 2-Institut National de la Recherche Agronomique ( INRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Center for TeleInFrastruktur ( CTIF ), Aalborg University [Denmark] ( AAU ), Savoirs, Textes, Langage (STL) - UMR 8163 ( STL ), Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), Indian Institute of Technology Madras ( IIT Madras ), Universidade Estadual Paulista Júlio de Mesquita ( UNESP ), Laboratoire de Génie Informatique et Ingénierie de Production ( LGI2P ), IMT - Mines Alès Ecole Mines - Télécom ( IMT - MINES ALES ), Institut geològic de Catalunya ( IGC ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Physiologie et Génomique des Poissons ( LPGP ), Institut National de la Recherche Agronomique ( INRA ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Politecnico di Milano [Milan], European Microsoft Innovation Center ( EMIC ), Laboratoire de Mécanique, Physique et Géosciences ( LMPG ), Université Le Havre Normandie ( ULH ), Normandie Université ( NU ) -Normandie Université ( NU ), University of Cambridge [UK] ( CAM ), Laboratoire de Probabilités et Modèles Aléatoires ( LPMA ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique et de Biologie Moléculaire et Cellulaire ( IGBMC ), Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Center for Mathematical Modeling ( CMM ), Universidad de Santiago de Chile [Santiago] ( USACH ), London School of Hygiene and Tropical Medicine ( LSHTM ), University of Occupational and Environmental Health [Kitakyushu] ( UEOH ), Indian Institute of Technology Delhi ( IIT Delhi ), Institut de Recherche sur les Phénomènes Hors Equilibre ( IRPHE ), Aix Marseille Université ( AMU ) -Ecole Centrale de Marseille ( ECM ) -Centre National de la Recherche Scientifique ( CNRS ), Universidade Federal de Pernambuco [Recife] ( UFPE ), Nanoscience Institute ( NEST ), Laboratory Of Immune Cell Biology ( LICB ), JRC Institute for Environment and Sustainability ( IES ), European Commission - Joint Research Centre [Ispra] ( JRC ), Bonn Universität [Bonn], Laboratorio Nacional de Computação Cientifica [Rio de Janeiro] ( LNCC / MCT ), Royal Institute of Technology [Stockholm] ( KTH ), National ICT Australia [Sydney] ( NICTA ), Institut d'Histoire et de Philosophie des Sciences et des Techniques ( IHPST ), Université Panthéon-Sorbonne ( UP1 ) -Département d'Etudes Cognitives - ENS Paris ( DEC ), École normale supérieure - Paris ( ENS Paris ) -École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ), Ghent University [Belgium] ( UGENT ), Children’s Hospital of Philadelphia ( CHOP ), Univeristy of Pennsylvania Medical School, Laboratoire de recherche en Hydrodynamique, Énergétique et Environnement Atmosphérique ( LHEEA ), École Centrale de Nantes ( ECN ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherche en Génie Civil et Mécanique ( GeM ), Université de Nantes ( UN ) -École Centrale de Nantes ( ECN ) -Centre National de la Recherche Scientifique ( CNRS ), Medical College of Georgia, Electronic Navigation Research Institute ( ENRI ), Department of Computer Science [KAIST] ( CS ), Korea Advanced Institute of Science and Technology ( KAIST ), Laboratoire de l'Accélérateur Linéaire ( LAL ), University of Massachusetts [Boston] ( UMass Boston ), Forouzanfar, Mohammad H, Alexander, Lily, Anderson, H. Ro, Bachman, Victoria F, Biryukov, Stan, Brauer, Michael, Burnett, Richard, Casey, Daniel, Coates, Matthew M, Cohen, Aaron, Delwiche, Kristen, Estep, Kara, Frostad, Joseph J, Kc, Astha, Kyu, Hmwe H, Moradi Lakeh, Maziar, Ng, Marie, Slepak, Erica Leigh, Thomas, Bernadette A, Wagner, Joseph, Aasvang, Gunn Marit, Abbafati, Cristiana, Ozgoren, Ayse Abbasoglu, Abd Allah, Foad, Abera, Semaw F, Aboyans, Victor, Abraham, Biju, Abraham, Jerry Puthenpurakal, Abubakar, Ibrahim, Abu Rmeileh, Niveen M. E, Aburto, Tania C, Achoki, Tom, Adelekan, Ademola, Adofo, Koranteng, Adou, Arsène K, Adsuar, José C, Afshin, Ashkan, Agardh, Emilie E, Al Khabouri, Mazin J, Al Lami, Faris H, Alam, Sayed Saidul, Alasfoor, Deena, Albittar, Mohammed I, Alegretti, Miguel A, Aleman, Alicia V, Alemu, Zewdie A, Alfonso Cristancho, Rafael, Alhabib, Samia, Ali, Raghib, Ali, Mohammed K, Alla, Françoi, Allebeck, Peter, Allen, Peter J, Alsharif, Ubai, Alvarez, Elena, Alvis Guzman, Nelson, Amankwaa, Adansi A, Amare, Azmeraw T, Ameh, Emmanuel A, Ameli, Omid, Amini, Heresh, Ammar, Walid, Anderson, Benjamin O, Antonio, Carl Abelardo T, Anwari, Palwasha, Cunningham, Solveig Argeseanu, Arnlöv, Johan, Arsenijevic, Valentina S. Arsic, Artaman, Al, Asghar, Rana J, Assadi, Reza, Atkins, Lydia S, Atkinson, Charle, Avila, Marco A, Awuah, Baffour, Badawi, Alaa, Bahit, Maria C, Bakfalouni, Talal, Balakrishnan, Kalpana, Balalla, Shivanthi, Balu, Ravi Kumar, Banerjee, Amitava, Barber, Ryan M, Barker Collo, Suzanne L, Barquera, Simon, Barregard, Lar, Barrero, Lope H, Barrientos Gutierrez, Tonatiuh, Basto Abreu, Ana C, Basu, Arindam, Basu, Sanjay, Basulaiman, Mohammed O, Ruvalcaba, Carolina Bati, Beardsley, Justin, Bedi, Neeraj, Bekele, Tolesa, Bell, Michelle L, Benjet, Corina, Bennett, Derrick A, Benzian, Habib, Bernabé, Eduardo, Beyene, Tariku J, Bhala, Neeraj, Bhalla, Ashish, Bhutta, Zulfiqar A, Bikbov, Bori, Abdulhak, Aref A. Bin, Blore, Jed D, Blyth, Fiona M, Bohensky, Megan A, Başara, Berrak Bora, Borges, Guilherme, Bornstein, Natan M, Bose, Dipan, Boufous, Soufiane, Bourne, Rupert R, Brainin, Michael, Brazinova, Alexandra, Breitborde, Nicholas J, Brenner, Hermann, Briggs, Adam D. M, Broday, David M, Brooks, Peter M, Bruce, Nigel G, Brugha, Traolach S, Brunekreef, Bert, Buchbinder, Rachelle, Bui, Linh N, Bukhman, Gene, Bulloch, Andrew G, Burch, Michael, Burney, Peter G. J, Campos Nonato, Ismael R, Campuzano, Julio C, Cantoral, Alejandra J, Caravanos, Jack, Cárdenas, Rosario, Cardis, Elisabeth, Carpenter, David O, Caso, Valeria, Castañeda Orjuela, Carlos A, Castro, Ruben E, Catalá López, Ferrán, Cavalleri, Fiorella, Çavlin, Alanur, Chadha, Vineet K, Chang, Jung Chen, Charlson, Fiona J, Chen, Honglei, Chen, Wanqing, Chen, Zhengming, Chiang, Peggy P, Chimed Ochir, Odgerel, Chowdhury, Rajiv, Christophi, Costas A, Chuang, Ting Wu, Chugh, Sumeet S, Cirillo, Massimo, Claßen, Thomas Kd, Colistro, Valentina, Colomar, Mercede, Colquhoun, Samantha M, Contreras, Alejandra G, Cooper, Cyru, Cooperrider, Kimberly, Cooper, Leslie T, Coresh, Josef, Courville, Karen J, Criqui, Michael H, Cuevas Nasu, Lucia, Damsere Derry, Jame, Danawi, Hadi, Dandona, Lalit, Dandona, Rakhi, Dargan, Paul I, Davis, Adrian, Davitoiu, Dragos V, Dayama, Anand, de Castro, E. Filipa, De la Cruz Góngora, Vanessa, De Leo, Diego, de Lima, Graça, Degenhardt, Louisa, Del Pozo Cruz, Borja, Dellavalle, Robert P, Deribe, Kebede, Derrett, Sarah, Jarlais, Don C. De, Dessalegn, Muluken, Deveber, Gabrielle A, Devries, Karen M, Dharmaratne, Samath D, Dherani, Mukesh K, Dicker, Daniel, Ding, Eric L, Dokova, Klara, Dorsey, E. Ray, Driscoll, Tim R, Duan, Leilei, Durrani, Adnan M, Ebel, Beth E, Ellenbogen, Richard G, Elshrek, Yousef M, Endres, Matthia, Ermakov, Sergey P, Erskine, Holly E, Eshrati, Babak, Esteghamati, Alireza, Fahimi, Saman, Faraon, Emerito Jose A, Farzadfar, Farshad, Fay, Derek F. J, Feigin, Valery L, Feigl, Andrea B, Fereshtehnejad, Seyed Mohammad, Ferrari, Alize J, Ferri, Cleusa P, Flaxman, Abraham D, Fleming, Thomas D, Foigt, Nataliya, Foreman, Kyle J, Paleo, Urbano Fra, Franklin, Richard C, Gabbe, Belinda, Gaffikin, Lynne, Gakidou, Emmanuela, Gamkrelidze, Amiran, Gankpé, Fortuné G, Gansevoort, Ron T, García Guerra, Francisco A, Gasana, Evariste, Geleijnse, Johanna M, Gessner, Bradford D, Gething, Pete, Gibney, Katherine B, Gillum, Richard F, Ginawi, Ibrahim A. M, Giroud, Maurice, Giussani, Giorgia, Goenka, Shifalika, Goginashvili, Ketevan, Dantes, Hector Gomez, Gona, Philimon, de Cosio, Teresita Gonzalez, González Castell, Dinorah, Gotay, Carolyn C, Goto, Atsushi, Gouda, Hebe N, Guerrant, Richard L, Gugnani, Harish C, Guillemin, Franci, Gunnell, David, Gupta, Rahul, Gupta, Rajeev, Gutiérrez, Reyna A, Hafezi Nejad, Nima, Hagan, Holly, Hagstromer, Maria, Halasa, Yara A, Hamadeh, Randah R, Hammami, Mouhanad, Hankey, Graeme J, Hao, Yuantao, Harb, Hilda L, Haregu, Tilahun Nigatu, Haro, Josep Maria, Havmoeller, Rasmu, Hay, Simon I, Hedayati, Mohammad T, Heredia Pi, Ileana B, Hernandez, Lucia, Heuton, Kyle R, Heydarpour, Pouria, Hijar, Martha, Hoek, Hans W, Hoffman, Howard J, Hornberger, John C, Hosgood, H. Dean, Hoy, Damian G, Hsairi, Mohamed, Hu, Guoqing, Hu, Howard, Huang, Cheng, Huang, John J, Hubbell, Bryan J, Huiart, Laetitia, Husseini, Abdullatif, Iannarone, Marissa L, Iburg, Kim M, Idrisov, Bulat T, Ikeda, Nayu, Innos, Kaire, Inoue, Manami, Islami, Farhad, Ismayilova, Samaya, Jacobsen, Kathryn H, Jansen, Henrica A, Jarvis, Deborah L, Jassal, Simerjot K, Jauregui, Alejandra, Jayaraman, Sudha, Jeemon, Panniyammakal, Jensen, Paul N, Jha, Vivekanand, Jiang, Fan, Jiang, Guohong, Jiang, Ying, Jonas, Jost B, Juel, Knud, Kan, Haidong, Roseline, Sidibe S. Kany, Karam, Nadim E, Karch, André, Karema, Corine K, Karthikeyan, Ganesan, Kaul, Anil, Kawakami, Norito, Kazi, Dhruv S, Kemp, Andrew H, Kengne, Andre P, Keren, Andre, Khader, Yousef S, Khalifa, Shams Eldin Ali Hassan, Khan, Ejaz A, Khang, Young Ho, Khatibzadeh, Shahab, Khonelidze, Irma, Kieling, Christian, Kim, Daniel, Kim, Sungroul, Kim, Yunjin, Kimokoti, Ruth W, Kinfu, Yohanne, Kinge, Jonas M, Kissela, Brett M, Kivipelto, Miia, Knibbs, Luke D, Knudsen, Ann Kristin, Kokubo, Yoshihiro, Kose, M. Rifat, Kosen, Soewarta, Kraemer, Alexander, Kravchenko, Michael, Krishnaswami, Sanjay, Kromhout, Han, Ku, Tiffany, Defo, Barthelemy Kuate, Bicer, Burcu Kucuk, Kuipers, Ernst J, Kulkarni, Chanda, Kulkarni, Veena S, Kumar, G. Anil, Kwan, Gene F, Lai, Taavi, Balaji, Arjun Lakshmana, Lalloo, Ratilal, Lallukka, Tea, Lam, Hilton, Lan, Qing, Lansingh, Van C, Larson, Heidi J, Larsson, Ander, Laryea, Dennis O, Lavados, Pablo M, Lawrynowicz, Alicia E, Leasher, Janet L, Lee, Jong Tae, Leigh, Jame, Leung, Ricky, Levi, Miriam, Li, Yichong, Li, Yongmei, Liang, Juan, Liang, Xiaofeng, Lim, Stephen S, Lindsay, M. Patrice, Lipshultz, Steven E, Liu, Shiwei, Liu, Yang, Lloyd, Belinda K, Logroscino, Giancarlo, London, Stephanie J, Lopez, Nancy, Lortet Tieulent, Joannie, Lotufo, Paulo A, Lozano, Rafael, Lunevicius, Raimunda, Ma, Jixiang, Ma, Stefan, Machado, Vasco M. P, Macintyre, Michael F, Magis Rodriguez, Carlo, Mahdi, Abbas A, Majdan, Marek, Malekzadeh, Reza, Mangalam, Srikanth, Mapoma, Christopher C, Marape, Marape, Marcenes, Wagner, Margolis, David J, Margono, Christopher, Marks, Guy B, Martin, Randall V, Marzan, Melvin B, Mashal, Mohammad T, Masiye, Felix, Mason Jones, Amanda J, Matsushita, Kunihiro, Matzopoulos, Richard, Mayosi, Bongani M, Mazorodze, Tasara T, Mckay, Abigail C, Mckee, Martin, Mclain, Abigail, Meaney, Peter A, Medina, Catalina, Mehndiratta, Man Mohan, Mejia Rodriguez, Fabiola, Mekonnen, Wubegzier, Melaku, Yohannes A, Meltzer, Michele, Memish, Ziad A, Mendoza, Walter, Mensah, George A, Meretoja, Atte, Mhimbira, Francis Apolinary, Micha, Renata, Miller, Ted R, Mills, Edward J, Misganaw, Awoke, Mishra, Santosh, Ibrahim, Norlinah Mohamed, Mohammad, Karzan A, Mokdad, Ali H, Mola, Glen L, Monasta, Lorenzo, Hernandez, Julio C. Montañez, Montico, Marcella, Moore, Ami R, Morawska, Lidia, Mori, Rintaro, Moschandreas, Joanna, Moturi, Wilkister N, Mozaffarian, Dariush, Mueller, Ulrich O, Mukaigawara, Mitsuru, Mullany, Erin C, Murthy, Kinnari S, Naghavi, Mohsen, Nahas, Ziad, Naheed, Aliya, Naidoo, Kovin S, Naldi, Luigi, Nand, Devina, Nangia, Vinay, Narayan, Km Venkat, Nash, Deni, Neal, Bruce, Nejjari, Chakib, Neupane, Sudan P, Newton, Charles R, Ngalesoni, Frida N, de Dieu Ngirabega, Jean, Nguyen, Grant, Nguyen, Nhung T, Nieuwenhuijsen, Mark J, Nisar, Muhammad I, Nogueira, José R, Nolla, Joan M, Nolte, Sandra, Norheim, Ole F, Norman, Rosana E, Norrving, Bo, Nyakarahuka, Luke, Oh, In Hwan, Ohkubo, Takayoshi, Olusanya, Bolajoko O, Omer, Saad B, Opio, John Nelson, Orozco, Ricardo, Pagcatipunan, Rodolfo S, Pain, Amanda W, Pandian, Jeyaraj D, Panelo, Carlo Irwin A, Papachristou, Christina, Park, Eun Kee, Parry, Charles D, Caicedo, Angel J. Paternina, Patten, Scott B, Paul, Vinod K, Pavlin, Boris I, Pearce, Neil, Pedraza, Lilia S, Pedroza, Andrea, Stokic, Ljiljana Pejin, Pekericli, Ayfer, Pereira, David M, Perez Padilla, Rogelio, Perez Ruiz, Fernando, Perico, Norberto, Perry, Samuel A. L, Pervaiz, Aslam, Pesudovs, Konrad, Peterson, Carrie B, Petzold, Max, Phillips, Michael R, Phua, Hwee Pin, Plass, Dietrich, Poenaru, Dan, Polanczyk, Guilherme V, Polinder, Suzanne, Pond, Constance D, Pope, C. Arden, Pope, Daniel, Popova, Svetlana, Pourmalek, Farshad, Powles, John, Prabhakaran, Dorairaj, Prasad, Noela M, Qato, Dima M, Quezada, Amado D, Quistberg, D. Alex A, Racapé, Lionel, Rafay, Anwar, Rahimi, Kazem, Rahimi Movaghar, Vafa, Rahman, Sajjad Ur, Raju, Murugesan, Rakovac, Ivo, Rana, Saleem M, Rao, Mayuree, Razavi, Homie, Reddy, K. Srinath, Refaat, Amany H, Rehm, Jürgen, Remuzzi, Giuseppe, Ribeiro, Antonio L, Riccio, Patricia M, Richardson, Lee, Riederer, Anne, Robinson, Margaret, Roca, Anna, Rodriguez, Alina, Rojas Rueda, David, Romieu, Isabelle, Ronfani, Luca, Room, Robin, Roy, Nobhojit, Ruhago, George M, Rushton, Lesley, Sabin, Nsanzimana, Sacco, Ralph L, Saha, Sukanta, Sahathevan, Ramesh, Sahraian, Mohammad Ali, Salomon, Joshua A, Salvo, Deborah, Sampson, Uchechukwu K, Sanabria, Juan R, Sanchez, Luz Maria, Sánchez Pimienta, Tania G, Sanchez Riera, Lidia, Sandar, Logan, Santos, Itamar S, Sapkota, Amir, Satpathy, Maheswar, Saunders, James E, Sawhney, Monika, Saylan, Mete I, Scarborough, Peter, Schmidt, Jürgen C, Schneider, Ione J. C, Schöttker, Ben, Schwebel, David C, Scott, James G, Seedat, Soraya, Sepanlou, Sadaf G, Serdar, Berrin, Servan Mori, Edson E, Shaddick, Gavin, Shahraz, Saeid, Levy, Teresa Shamah, Shangguan, Siyi, She, Jun, Sheikhbahaei, Sara, Shibuya, Kenji, Shin, Hwashin H, Shinohara, Yukito, Shiri, Rahman, Shishani, Kawkab, Shiue, Ivy, Sigfusdottir, Inga D, Silberberg, Donald H, Simard, Edgar P, Sindi, Shireen, Singh, Abhishek, Singh, Gitanjali M, Singh, Jasvinder A, Skirbekk, Vegard, Sliwa, Karen, Soljak, Michael, Soneji, Samir, Søreide, Kjetil, Soshnikov, Sergey, Sposato, Luciano A, Sreeramareddy, Chandrashekhar T, Stapelberg, Nicolas J. 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Alex A., Rahimi-Movaghar, Vafa, Ur Rahman, Sajjad, Rana, Saleem M., Refaat, Amany H., Ribeiro, Antonio L., Riccio, Patricia M., Rojas-Rueda, David, Ruhago, George M., Sacco, Ralph L., Salomon, Joshua A., Sampson, Uchechukwu K., Sanabria, Juan R., Sánchez-Pimienta, Tania G., Sanchez-Riera, Lidia, Santos, Itamar S., Saunders, James E., Saylan, Mete I., Schmidt, Jürgen C., Schneider, Ione J.C., Schwebel, David C., Scott, James G., Sepanlou, Sadaf G., Servan-Mori, Edson E., Shamah Levy, Teresa, Shin, Hwashin H., Sigfusdottir, Inga D., Silberberg, Donald H., Simard, Edgar P., Singh, Gitanjali M., Singh, Jasvinder A., Sposato, Luciano A., Sreeramareddy, Chandrashekhar T., Stapelberg, Nicolas J.C., Stein, Dan J., Stein, Murray B., Sunguya, Bruno F., Sykes, Bryan L., Tabb, Karen M., Talongwa, Roberto T., Te Ao, Braden J., Teixeira, Carolina M., Téllez Rojo, Martha M., Terkawi, Abdullah S., Texcalac-Sangrador, José Lui, Thackway, Sarah V., Thorne-Lyman, Andrew L., Thrift, Amanda G., Thurston, George D., Towbin, Jeffrey A., Tran, Bach X., Tsala Dimbuene, Zacharie, Uchendu, Uche S., Ukwaja, Kingsley N., Uzun, Selen B., Van De Vijver, Steven, Van Gool, Coen H., Van Os, Jim, Varakin, Yuri Y., Vasankari, Tommi J., Vasconcelos, Ana Maria N., Vavilala, Monica S., Veerman, Lennert J., Velasquez-Melendez, Gustavo, Venketasubramanian, N., Violante, Francesco S., Victorovich Vlassov, Vasiliy, Wagner, Gregory R., Waller, Stephen G., Wallin, Mitchell T., Warouw, Tati S., Watts, Charlotte H., Weintraub, Robert G., Whiteford, Harvey A., Wilkinson, James D., Williams, Hywel C., Williams, Thomas N., Woldeyohannes, Solomon M., Wolfe, Charles D.A., Wong, John Q., Woolf, Anthony D., Wright, Jonathan L., Yan, Lijing L., Yentür, Gökalp K., Yoon, Seok-Jun, Younis, Mustafa Z., Zaki, Maysaa E., Zunt, Joseph R., Lopez, Alan D., and Temesgen, A.M.
Subjects: Male, Fine particulate matter, Nutrition and Disease, MESH : Sanitation, Health Behavior, Diseases, MESH: Metabolic Diseases, MESH: Global Health, 030204 cardiovascular system & hematology, MESH: Risk Assessment, Global Health, MESH : Nutritional Status, MESH: Occupational Exposure, 0302 clinical medicine, Unsafe Sex, MESH: Risk Factors, Risk Factors, Voeding en Ziekte, Medicine, Air-pollution, MESH : Female, 030212 general & internal medicine, MESH : Risk Assessment, Sanitation, Wasting, 2. Zero hunger, Factors de risc en les malalties, Medicine (all), [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, MESH : Occupational Diseases, MESH: Nutritional Status, All-cause mortality, MESH : Risk Factors, humanities, Environmental Exposure, Female, Humans, Metabolic Diseases, Nutritional Status, Occupational Diseases, Occupational Exposure, Risk Assessment, Tobacco smoking, 3. Good health, Nutritional Statu, MESH : Occupational Exposure, MESH : Metabolic Diseases, Cohort, medicine.symptom, Risk assessment, Blood-pressure, Human, MESH: Occupational Diseases, Risk factors in diseases, Coronary-heart-disease, MESH : Male, MESH: Health Behavior, MESH: Environmental Exposure, Population health, Body-mass index, 03 medical and health sciences, Household cooking, Cardiovascular-disease, Environmental health, General & Internal Medicine, parasitic diseases, Life Science, MESH: Sanitation, Risk factor, MESH : Health Behavior, VLAG, GBD2013, MESH: Humans, business.industry, Risk Factor, Global Burden of Disease Study, 79 behavioural, environmental and occupational, and metabolic risks, Long-term exposure, MESH : Humans, CAUSE-SPECIFIC MORTALITY, MESH: Male, Metabolic Disease, Occupational Disease, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, MALE BRITISH DOCTORS, Years of potential life lost, Relative risk, Malalties, MESH : Global Health, OUTDOOR AIR-POLLUTION, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH : Environmental Exposure, MESH: Female
Abstract: Summary Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian metaregression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5−89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks. Funding Bill & Melinda Gates Foundation. Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the fi rst of a series of annual updates of the GBD. Risk factor quantifi cation, particularly of modifi able risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the fi rst level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular fi ltration rate. For most risks, data for exposure were synthesised with a Bayesian metaregression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5−89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks. Funding Bill & Melinda Gates Foundation.
Published: 2015
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49. Changes in health in England, with analysis by English regions and areas of deprivation, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Author: Ivy Shiue, Charis Gresser, S. M. Biryukov, Alison Tedstone, Harry Rutter, Matthew M Coates, Bernadette M. Hannigan, Martin McKee, Austin E Schumacher, Mohammad H. Forouzanfar, Henrik Møller, Rupert R A Bourne, Michele E. Murdoch, John N Newton, Carol Brayne, Julia A Critchley, Roderick J. Hay, Anthony D. Woolf, Theo Vos, Harry Hemingway, Derek F J Fay, Majid Ezzati, Adrian Davis, Charles D.A. Wolfe, Amanda J. Mason-Jones, Adam D M Briggs, Daniel C Casey, Nigel Bruce, Rajiv Chowdhury, Daniel Pope, Kyle J Foreman, Jürgen C Schmidt, Heidi J. Larson, Katharine J Looker, Daniel Dicker, Simon I. Hay, Thomas Fürst, Andrew Hughes, Jonathan Valabhji, Kazem Rahimi, Summer Lockett Ohno, Mohsen Naghavi, Traolach S. Brugha, Wagner Marcenes, Alina Rodriguez, Eduardo Bernabé, Kamaldeep Bhui, Hywel C Williams, Paul Elliott, Fiona E. Matthews, Ryan M Barber, Simon Capewell, Russell Ecob, David Gunnell, Michael Burch, Ibrahim Abubakar, Paul I. Dargan, H. Ross Anderson, Mark A. Green, Liam Smeeth, Jeffrey D. Stanaway, Maya S Fraser, Felix Greaves, Neil Pearce, Amitava Banerjee, Ronan A Lyons, R. Ali, Charles R. Newton, Mukesh Dherani, Peter Scarborough, Kevin A. Fenton, Cyrus Cooper, Christopher J L Murray, Frédéric B. Piel, Haidong Wang, Raimundas Lunevicius, Derrick A Bennett, Brayne, Carol [0000-0001-5307-663X], Chowdhury, Rajiv [0000-0003-4881-5690], Matthews, Fiona [0000-0002-1728-2388], and Apollo - University of Cambridge Repository
Subjects: Gerontology, Male, Health Status, Disease, 030204 cardiovascular system & hematology, 0302 clinical medicine, Risk Factors, Cause of Death, Poverty Areas, Prevalence, Medicine, Life Tables, 030212 general & internal medicine, media_common, Aged, 80 and over, Medicine(all), DEMENTIA, Mortality rate, Incidence, PRIMARY-CARE, DEATH, Public Health, Global Health, Social Medicine and Epidemiology, 11 Medical And Health Sciences, General Medicine, ALZHEIMERS-DISEASE, England, Female, Life Sciences & Biomedicine, medicine.medical_specialty, INTEGRATED APPROACH, 187 COUNTRIES, 03 medical and health sciences, Medicine, General & Internal, Life Expectancy, General & Internal Medicine, media_common.cataloged_instance, Humans, European union, Health policy, Aged, Science & Technology, business.industry, MORTALITY, Public health, Health Status Disparities, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Years of potential life lost, PRIMARY LIVER-CANCER, Attributable risk, Life expectancy, L510 Health & Welfare, business, Demography
Abstract: Background In the Global Burden of Disease Study 2013 (GBD 2013), knowledge about health and its determinants has been integrated into a comparable framework to inform health policy. Outputs of this analysis are relevant to current policy questions in England and elsewhere, particularly on health inequalities. We use GBD 2013 data on mortality and causes of death, and disease and injury incidence and prevalence to analyse the burden of disease and injury in England as a whole, in English regions, and within each English region by deprivation quintile. We also assess disease and injury burden in England attributable to potentially preventable risk factors. England and the English regions are compared with the remaining constituent countries of the UK and with comparable countries in the European Union (EU) and beyond. Methods We extracted data from the GBD 2013 to compare mortality, causes of death, years of life lost (YLLs), years lived with a disability (YLDs), and disability-adjusted life-years (DALYs) in England, the UK, and 18 other countries (the first 15 EU members [apart from the UK] and Australia, Canada, Norway, and the USA [EU15+]). We extended elements of the analysis to English regions, and subregional areas defined by deprivation quintile (deprivation areas). We used data split by the nine English regions (corresponding to the European boundaries of the Nomenclature for Territorial Statistics level 1 [NUTS 1] regions), and by quintile groups within each English region according to deprivation, thereby making 45 regional deprivation areas. Deprivation quintiles were defined by area of residence ranked at national level by Index of Multiple Deprivation score, 2010. Burden due to various risk factors is described for England using new GBD methodology to estimate independent and overlapping attributable risk for five tiers of behavioural, metabolic, and environmental risk factors. We present results for 306 causes and 2337 sequelae, and 79 risks or risk clusters. Findings Between 1990 and 2013, life expectancy from birth in England increased by 5·4 years (95% uncertainty interval 5·0-5·8) from 75·9 years (75·9-76·0) to 81·3 years (80·9-81·7); gains were greater for men than for women. Rates of age-standardised YLLs reduced by 41·1% (38·3-43·6), whereas DALYs were reduced by 23·8% (20·9-27·1), and YLDs by 1·4% (0·1-2·8). For these measures, England ranked better than the UK and the EU15+ means. Between 1990 and 2013, the range in life expectancy among 45 regional deprivation areas remained 8·2 years for men and decreased from 7·2 years in 1990 to 6·9 years in 2013 for women. In 2013, the leading cause of YLLs was ischaemic heart disease, and the leading cause of DALYs was low back and neck pain. Known risk factors accounted for 39·6% (37·7-41·7) of DALYs; leading behavioural risk factors were suboptimal diet (10·8% [9·1-12·7]) and tobacco (10·7% [9·4-12·0]). Interpretation Health in England is improving although substantial opportunities exist for further reductions in the burden of preventable disease. The gap in mortality rates between men and women has reduced, but marked health inequalities between the least deprived and most deprived areas remain. Declines in mortality have not been matched by similar declines in morbidity, resulting in people living longer with diseases. Health policies must therefore address the causes of ill health as well as those of premature mortality. Systematic action locally and nationally is needed to reduce risk exposures, support healthy behaviours, alleviate the severity of chronic disabling disorders, and mitigate the effects of socioeconomic deprivation. Funding Bill & Melinda Gates Foundation and Public Health England. © 2015 Newton et al. Open Access article distributed under the terms of CC BY. 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Published: 2015
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50. Associations between Phytoestrogens, Glucose Homeostasis, and Risk of Diabetes in Women: A Systematic Review and Meta-Analysis

Author: Wichor M. Bramer, Oscar H. Franco, Trudy Voortman, Rajiv Chowdhury, Fariba Ahmadizar, Anton J.M. Roks, Marija Glisic, Taulant Muka, A.H. Jan Danser, Natyra Kastrati, Valentina Gonzalez-Jaramillo, Epidemiology, Erasmus MC other, and Internal Medicine
Subjects: Adult, Blood Glucose, endocrine system, Population, Medicine (miscellaneous), Physiology, 030209 endocrinology & metabolism, Phytoestrogens, Type 2 diabetes, Review, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Insulin resistance, SDG 3 - Good Health and Well-being, Risk Factors, medicine, Glucose homeostasis, Homeostasis, Humans, Insulin, 030212 general & internal medicine, Prospective Studies, education, Glycemic, Aged, Randomized Controlled Trials as Topic, Aged, 80 and over, education.field_of_study, Nutrition and Dietetics, business.industry, food and beverages, Fasting, Isoflavones, Middle Aged, medicine.disease, Observational Studies as Topic, chemistry, Diabetes Mellitus, Type 2, Dietary Supplements, Homeostatic model assessment, Female, Insulin Resistance, business, Food Science
Abstract: Phytoestrogens might have advantageous effects on diabetes in women. We performed a systematic review and meta-analysis to determine the effect of phytoestrogens on glucose homeostasis and the risk of type 2 diabetes (T2D) among women. Randomized controlled trials (RCTs) and prospective observational studies that assessed associations of phytoestrogens (supplementation, dietary intake, or biomarkers) with fasting glucose or insulin, homeostatic model assessment of insulin resistance (HOMA-IR), or with the risk of T2D were included. We identified 18 RCTs (n = 1687 individuals) investigating the effect of phytoestrogen supplementation on glucose homeostasis and 9 prospective population-based studies (n = 212,796 individuals) examining the association between phytoestrogen intake and the risk of T2D. Compared with placebo, phytoestrogen supplementation resulted in improvements in fasting glucose and HOMA-IR: the pooled mean differences of changes were -0.12 mmol/L (95% CI: -0.20, -0.03 mmol/L) and -0.24 mmol/L (95% CI: -0.45, -0.03 mmol/L), respectively. Although there was no significant decrease in insulin concentrations with overall phytoestrogen supplementation, the pooled mean difference in changes was -0.99 pmol/L (95% CI: -4.65, 2.68 pmol/L). However, the results of RCTs varied by type of phytoestrogens: soy-derived isoflavones and genistein improved glucose homeostasis, whereas isoflavone mix and daidzein had no effect or were associated with an adverse glycemic profile. Higher dietary phytoestrogen intake was associated with a 10% lower risk of developing T2D in observational studies (pooled RR: 0.90; 95% CI: 0.85, 0.96; for the highest compared with the lowest quantiles). Results were similar when the analyses were restricted to only medium- and high-quality studies. Overall, phytoestrogens may have a positive influence on glycemia and could be used for diabetes prevention in women. However, for some individual types of phytoestrogens, such as mixed isoflavones, caution is needed in recommending their use in women, because their use could lead to an adverse glycemic profile in women.
Published: 2018

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