Large-scale observational studies in diverse populations

Lead Research Organisation: University of Oxford

Abstract

Experience in Western countries has shown that large population-based prospective studies are a valuable way of investigating many slow-acting causes of common chronic diseases. The PHRU is collaborating with researchers in low and middle income countries to generate reliable evidence about the importance of common risk factors for premature death (such as smoking, alcohol, obesity and hypertension).
Our previous research has demonstrated the hazards of prolonged smoking and the benefits of stopping smoking in high-income countries; and ongoing studies, involving 1.4 million participants, are currently assessing the risks of smoking in Mexico, Cuba and India. In 2009 and 2014 we reported that excessive alcohol consumption (chiefly vodka) was responsible for most premature deaths in Russia and this immediately prompted new public health strategies to limit heavy alcohol consumption. Our study in Mexico (where one-third of men and one-half of women are obese) has shown that uncontrolled diabetes causes at least one third of all deaths between 35 and 74 years of age.

Technical Summary

Over a period of decades, large population-based observational studies have helped identify several major 'classic causes' of premature death from non-communicable disease (NCD), including smoking, hypertension, obesity (adiposity), harmful alcohol use, dyslipidaemia, diabetes, poor diet and physical inactivity. However, the effects of such factors vary greatly from one population to another. There is still substantial uncertainty as to how important these factors are in different settings, and how their importance is changing with time. Direct evidence from low-and middle-income countries (LMICs) is important as it may in the long run improve local and regional NCD control strategies and actions. However, such evidence is lacking. Indeed, at present, global estimates of the importance of classic causes depend mainly on mathematical extrapolation from findings in high-income countries. LMIC findings may change global estimates significantly, thus strengthening our understanding of the NCD burden and the local relevance of causes.
During the 1990s/2000s, therefore, PHRU in collaboration with local investigators set up large prospective studies in Chennai (500,000 adults), Kerala (400,000), Russia (200,000 adults), Cuba (150,000) and Mexico City (150,000 with blood). Recruitment finished in Cuba in 2000, Chennai in 2001, Kerala in 2002, Mexico in 2004 and Russia in 2008. Follow-up involves fieldwork together, where possible, with electronic linkage to national mortality records. Resurveys among subsets of survivors have been conducted or are planned in each cohort. Some 53,000 deaths have already been recorded in Chennai, 33,000 in Kerala, 12,000 in Cuba and 20,000 in Mexico. In Mexico, further linkage to non-fatal health records is being conducted and validated, while the availability of blood samples collected at baseline in nearly all participants will allow (funding permitting) for the measurement of a large range of biochemical and genetic markers. These cohorts have already demonstrated the value of studying classic causes of premature death in different settings, for example by demonstrating the risks from hazardous drinking in Russia (which, together with smoking, may well account for 3/4 of all male deaths before age 75) and the risks from diabetes in Mexico (where diabetes was found to be a cause of at least one third of all deaths between 35 and 74 years of age, twice previous indirect estimates based on evidence from other populations).
The prospective studies PHRU has set up will help monitor the evolution of the worldwide epidemics of premature death from classic causes, while the availability of blood samples in the Mexico study affords the further opportunity for discovery of novel genetic and metabolic pathways and their relevance for premature death. The studies have been set up, follow-up has accumulated, collaboration is assured and PHRU will, during the next 5 years, continue to collaborate closely with the national PIs to generate reliable analyses and publications. These reports will reach the highest levels of the governments concerned as well as reaching the wider population.

Publications

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Alegre-Díaz J (2016) Diabetes and Cause-Specific Mortality in Mexico City. in The New England journal of medicine

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Di Angelantonio E (2017) Body-mass index and all-cause mortality - Authors' reply in The Lancet

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Gnatiuc L (2017) Adiposity and Blood Pressure in 110 000 Mexican Adults. in Hypertension (Dallas, Tex. : 1979)

 
Description WHO Global Hearts Initiative
Geographic Reach Multiple continents/international 
Policy Influence Type Gave evidence to a government review
Impact Our work has informed the World Health Organisation Global Hearts Initiative to address cardiovascular disease in low and middle income countries. Government policy on non-communicable disease control in Cuba, Russia and India
 
Description BHF Centre for Research Excellence 
Organisation University of Oxford
Department BHF Centre of Research Excellence
Country United Kingdom 
Sector Academic/University 
PI Contribution n/a
Collaborator Contribution funding
Impact Support for Dr Ben Lacey to work on routinely-collected electronic health records in preparation for fellowship
Start Year 2018
 
Description CDC Foundation 
Organisation CDC Foundation
Country Georgia 
Sector Public 
PI Contribution Co-principal Investigator
Collaborator Contribution The CDC Foundation and Amgen are partnering on a new global cardiovascular health initiative to support independent epidemiological research by the University of Oxford and technological and evaluation research by the Centers for Disease Control and Prevention (CDC).
Impact none yet
Start Year 2018
 
Description CDC Foundation 
Organisation Center for Disease Control Foundation
Country Georgia 
Sector Charity/Non Profit 
PI Contribution academic partnership
Collaborator Contribution academic partnership
Impact n/a
Start Year 2016
 
Description Ethnic differences in the association between smoking and lung cancer: a comparison between Korea and the UK 
Organisation Yonsei University
Country Korea, Republic of 
Sector Academic/University 
PI Contribution Statistical and epidemiological expertise
Collaborator Contribution Epidemiological expertise and data
Impact Peer-reviewed publciations
Start Year 2017
 
Description Middle-East Cohort Studies Collaboration 
Organisation New York University Abu Dhabi
Country United Arab Emirates 
Sector Academic/University 
PI Contribution Statistical and epidemiological expertise
Collaborator Contribution Sharing of results from individual studies for preparation of manuscripts for publication
Impact n/a
Start Year 2017
 
Description NIHR Oxford BRC 
Organisation Oxford University Hospitals NHS Foundation Trust
Department NIHR Oxford Biomedical Research Centre
Country United Kingdom 
Sector Public 
PI Contribution Personal award
Collaborator Contribution funding
Impact Support for Dr Ben Lacey to work on large-scale observation studies
Start Year 2017
 
Description UK Biobank Renal Outcomes Group 
Organisation UK Biobank
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Member of working group
Collaborator Contribution They run it
Impact N/A
Start Year 2016
 
Description Cyber Security in the UAE 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Undergraduate students
Results and Impact science communicator on the UAE 'CyberQuest' project. This is a national competition for University/ high school students run by the Secret Intelligence Agency across the UAE. The Edinburgh International Science Festival was hired by the UAE government to design and teach one week of cybersecurity modules in order to prepare the kids for the competition. Prizes include things like full scholarships to study Cyber security at some of the top institutions in the world, and MacBook pro's etc. I was designated a class of 25 students aged 18+ and I taught them the following modules:
- Linux basics
- Port Scanning
- Firewalls
- Phishing Basic
- Phishing advanced
- Information gathering
- Web hacking basics
- Using wire-shark
- Web hacking advanced
- Securing web Apps
Each module would consist of about 2 hours of teaching time (using simulated online environments created by the EISF team) and then a timed, online assessment at the end. The test scores are combined for the whole 'training camp' and used to decide which children are through to the final competition. In April 2017, I was based in Abu Dhabi (8th-12th of April), but this January (6th-10th of January, 2018) I was based in Fujairah - a more conservative region in the North of the country.
Year(s) Of Engagement Activity 2017
 
Description Edinburgh International Science Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact However, for the past few years EISF has been running the same events in the UAE at the Abu Dhabi Science Festival (more info: https://www.adsftickets.com ). I first went out to the UAE for two weeks in November 2014. I usually run an event called 'ER Surgery' which involves teaching children aged 8-12 years about medicine using a simulated surgical environment - e.g. removing pretend 'gallstones' from a manikin using laparoscopy. In Edinburgh, I worked as a Science Communicator, whereas in Abu Dhabi (2014) I worked as a Team Leader, which involved teaching science communicators to run the workshops themselves. These science communicators were all National UAE citizens studying science and engineering at University, and working as a science communicator at the ADSF was a mandatory part of their University degree.
Year(s) Of Engagement Activity 2016,2017