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Background: Industrialised countries had varied responses to the COVID-19 pandemic, which may lead to different death tolls from COVID-19 and other diseases. Methods: We applied an ensemble of 16 Bayesian probabilistic models to vital statistics data to estimate the number of weekly deaths if the pandemic had not occurred for 40 industrialised countries and US states from mid-February 2020 through mid-February 2021. We subtracted these estimates from the actual number of deaths to calculate the impacts of the pandemic on all-cause mortality. Results: Over this year, there were 1,410,300 (95% credible interval 1,267,600-1,579,200) excess deaths in these countries, equivalent to a 15% (14-17) increase, and 141 (127-158) additional deaths per 100,000 people. In Iceland, Australia and New Zealand, mortality was lower than would be expected in the absence of the pandemic, while South Korea and Norway experienced no detectable change. The USA, Czechia, Slovakia and Poland experienced >20% higher mortality. Within the USA, Hawaii experienced no detectable change in mortality and Maine a 5% increase, contrasting with New Jersey, Arizona, Mississippi, Texas, California, Louisiana and New York which experienced >25% higher mortality. Mid-February to the end of May 2020 accounted for over half of excess deaths in Scotland, Spain, England and Wales, Canada, Sweden, Belgium, the Netherlands and Cyprus, whereas mid-September 2020 to mid-February 2021 accounted for >90% of excess deaths in Bulgaria, Croatia, Czechia, Hungary, Latvia, Montenegro, Poland, Slovakia and Slovenia. In USA, excess deaths in the northeast were driven mainly by the first wave, in southern and southwestern states by the summer wave, and in the northern plains by the post-September period. Conclusions: Prior to widespread vaccine-acquired immunity, minimising the overall death toll of the pandemic requires policies and non-pharmaceutical interventions that delay and reduce infections, effective treatments for infected patients, and mechanisms to continue routine health care.

Background: There is limited data with high spatial granularity on how mortality and longevity have changed in English communities. We estimated trends from 2002 to 2019 in life expectancy and probabilities of death at different ages for all 6,791 English middle-layer super output areas (MSOAs). Methods: We used de-identified data for all deaths in England from 2002 to 2019 with information on age, sex and MSOA of residence, and population counts by age, sex and MSOA. We used a Bayesian hierarchical model to obtain estimates of age-specific death rates by sharing information across age groups, MSOAs and years. We used life table methods to calculate life expectancy at birth and probabilities of death in different ages by sex and MSOA. Results: In 2002-2006 and 2006-2010, the vast majority of MSOAs experienced a life expectancy increase for both sexes. In 2010-2014, female life expectancy decreased in 351 (5%) of MSOAs. By 2014-2019, the number of MSOAs with declining life expectancy was 1,270 (19%) for women and 784 (12%) for men. The life expectancy increase from 2002 to 2019 was smaller where life expectancy had been lower in 2002, mostly northern urban MSOAs, and larger where life expectancy had been higher in 2002, mostly MSOAs in and around London. As a result of these trends, the gap between the 1st and 99th percentiles of MSOA life expectancy for women increased from 10.7 (95% credible interval 10.4-10.9) in 2002 to reach 14.2 (13.9-14.5) years in 2019, and from 11.5 (11.3-11.7) years to 13.6 (13.4-13.9) years for men. Interpretation: In many English communities, life expectancy declined in the years prior to the Covid-19 pandemic. To ensure that this trend does not continue there is a need for pro-equity economic and social policies, and greater investment on public health and healthcare.

Patients with type-2 diabetes mellitus (T2DM) often live with and develop multiple co-occurring conditions, namely multimorbidity, with diffuse impacts on clinical care and patient quality of life. However, literature characterising T2DM-related multimorbidity patterns is limited. This review summarises the findings from the emerging literature characterising and quantifying the association of T2DM with multimorbidity clusters. Our findings reveal three dominant cluster types appearing in patients with T2DM-related multimorbidity, such as cardiometabolic precursor conditions, vascular conditions, and mental health conditions. We recommend that holistic patient care centres around early detection of other comorbidities and consideration of wider risk factors, while future research should focus on the temporality of T2DM-related multimorbidity trajectories.

Background The prevalence of diabetes has increased in the UK and other high-income countries alongside a substantial decline in cardiovascular mortality. Yet data are scarce on how these trends have changed the causes of death in people with diabetes who have traditionally died primarily of vascular causes. We estimated how all-cause mortality and cause-specific mortality in people with diabetes have changed over time, how the composition of the mortality burden has changed, and how this composition compared with that of the non-diabetes population. Methods In this epidemiological analysis of primary care records, we identified 313 907 individuals with diabetes in the Clinical Practice Research Datalink, a well described primary care database, between 2001 to 2018, and linked these data to UK Office for National Statistics mortality data. We assembled serial cross sections with longitudinal follow-up to generate a mixed prevalence and incidence study population of patients with diabetes. We used discretised Poisson regression models to estimate annual death rates for deaths from all causes and 12 specific causes for men and women with diabetes. We also identified age-matched and sex matched (1:1) individuals without diabetes from the same dataset and estimated mortality rates in this group. Findings Between Jan 1, 2001, and Oct 31, 2018, total mortality declined by 32% in men and 31% in women with diagnosed diabetes. Death rates declined from 40·7 deaths per 1000 person-years to 27·8 deaths per 1000 person-years in men and from 42·7 deaths per 1000 person-years to 29·5 deaths per 1000 person-years in women with diagnosed diabetes. We found similar declines in individuals without diabetes, hence the gap in mortality between those with and without diabetes was maintained over the study period. Cause-specific death rates declined in ten of the 12 cause groups, with exceptions in dementia and liver disease, which increased in both populations. The large decline in vascular disease death rates led to a transition from vascular causes to cancers as the leading contributor to death rates in individuals with diagnosed diabetes and to the gap in death rates between those with and without diabetes. Interpretation The decline in vascular death rates has been accompanied by a diversification of causes in individuals with diagnosed diabetes and a transition from vascular diseases to cancers as the leading contributor to diabetes-related death. Clinical and preventative approaches must reflect this trend to reduce the excess mortality risk in individuals with diabetes.v

IMPORTANCE: Soft drinks are frequently consumed but if they are associated with mortality risk in European populations is unknown. OBJECTIVE: To examine the association between total, sugar-sweetened, and artificially-sweetened soft drinks consumption and subsequent total and cause-specific mortality. DESIGN: Population based prospective cohort study. SETTING: 10 European countries. PARTICIPANTS: 451,743 men and women from the European Prospective Investigation into Cancer and Nutrition. EXPOSURE: Soft drinks consumption (total, sugar-sweetened, artificially-sweetened). MAIN OUTCOMES AND MEASURES: Total and cause-specific mortality. Hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using multivariable Cox proportional hazards models adjusted for other mortality risk factors. RESULTS: During a mean follow up of 16.4 years, 41,693 deaths occurred. Higher all-cause mortality was found for participants consuming ≥2 glasses/day (versus consumers of

Importance: Soft drinks are frequently consumed, but whether this consumption is associated with mortality risk is unknown and has been understudied in European populations to date. Objective: To examine the association between total, sugar-sweetened, and artificially sweetened soft drink consumption and subsequent total and cause-specific mortality. Design, Setting, and Participants: This population-based cohort study involved participants (n = 451743 of the full cohort) in the European Prospective Investigation into Cancer and Nutrition (EPIC), an ongoing, large multinational cohort of people from 10 European countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom), with participants recruited between January 1, 1992, and December 31, 2000. Excluded participants were those who reported cancer, heart disease, stroke, or diabetes at baseline; those with implausible dietary intake data; and those with missing soft drink consumption or follow-up information. Data analyses were performed from February 1, 2018, to October 1, 2018. Exposure: Consumption of total, sugar-sweetened, and artificially sweetened soft drinks. Main Outcomes and Measures: Total mortality and cause-specific mortality. Hazard ratios (HRs) and 95% CIs were estimated using multivariable Cox proportional hazards regression models adjusted for other mortality risk factors. Results: In total, 521 330 individuals were enrolled. Of this total, 451743 (86.7%) were included in the study, with a mean (SD) age of 50.8 (9.8) years and with 321081 women (71.1%). During a mean (range) follow-up of 16.4 (11.1 in Greece to 19.2 in France) years, 41693 deaths occurred. Higher all-cause mortality was found among participants who consumed 2 or more glasses per day (vs consumers of

Background Life expectancy inequalities in England have increased steadily since the 1980s. Our aim was to investigate how much deaths from different diseases and injuries and at different ages have contributed to this rise to inform policies that aim to reduce health inequalities. Methods We used vital registration data from the Office for National Statistics on population and deaths in England, by underlying cause of death, from 2001 to 2016, stratified by sex, 5-year age group, and decile of the Index of Multiple Deprivation (based on the ranked scores of Lower Super Output Areas in England in 2015). We grouped the 7·65 million deaths by their assigned International Classification of Diseases (10th revision) codes to create categories of public health and clinical relevance. We used a Bayesian hierarchical model to obtain robust estimates of cause-specific death rates by sex, age group, year, and deprivation decile. We calculated life expectancy at birth by decile of deprivation and year using life-table methods. We calculated the contributions of deaths from each disease and injury, in each 5-year age group, to the life expectancy gap between the most deprived and affluent deciles using Arriaga's method. Findings The life expectancy gap between the most affluent and most deprived deciles increased from 6·1 years (95% credible interval 5·9–6·2) in 2001 to 7·9 years (7·7–8·1) in 2016 in females and from 9·0 years (8·8–9·2) to 9·7 years (9·6–9·9) in males. Since 2011, the rise in female life expectancy has stalled in the third, fourth, and fifth most deprived deciles and has reversed in the two most deprived deciles, declining by 0·24 years (0·10–0·37) in the most deprived and 0·16 years (0·02–0·29) in the second-most deprived by 2016. Death rates from every disease and at every age were higher in deprived areas than in affluent ones in 2016. The largest contributors to life expectancy inequalities were deaths in children younger than 5 years (mostly neonatal deaths), respiratory diseases, ischaemic heart disease, and lung and digestive cancers in working ages, and dementias in older ages. From 2001 to 2016, the contributions to inequalities declined for deaths in children younger than 5 years, ischaemic heart disease (for both sexes), and stroke and intentional injuries (for men), but increased for most other causes. Interpretation Recent trends in life expectancy in England have not only resulted in widened inequalities but the most deprived communities are now seeing no life expectancy gain. These inequalities are driven by a diverse group of diseases that can be effectively prevented and treated. Adoption of the principle of proportionate universalism to prevention and health and social care can postpone deaths into older ages for all communities and reduce life expectancy inequalities.

Objective: An industry levy on sugar-sweetened beverages (SSB) was implemented in the UK in 2018. One year later, Brexit is likely to change the UK trade regime with potential implications for sugar price. We modelled the effect of potential changes in sugar price due to Brexit on SSB levy impacts upon CHD mortality and inequalities. Design: We modelled a baseline SSB levy scenario; an SSB levy under ‘soft’ Brexit, where the UK establishes a free trading agreement with the EU; and an SSB levy under ‘hard’ Brexit, in which World Trade Organization tariffs are applied. We used the previously validated IMPACT Food Policy model and probabilistic sensitivity analysis to estimate the effect of each scenario on CHD deaths prevented or postponed and life-years gained, stratified by age, sex and socio-economic circumstance, in 2021. Setting: England. Subjects: Adults aged 25 years or older. Results: The SSB levy was associated with approximately 370 (95 % uncertainty interval 220, 560) fewer CHD deaths and 4490 (2690, 6710) life-years gained in 2021. Associated reductions in CHD mortality were 4 and 8 % greater under ‘soft’ and ‘hard’ Brexit scenarios, respectively. The SSB levy was associated with approximately 110 (50, 190) fewer CHD deaths in the most deprived quintile compared with 60 (20, 100) in the most affluent, under ‘hard’ Brexit. Conclusions: Our study found the SSB levy resilient to potential effects of Brexit upon sugar price. Even under ‘hard’ Brexit, the SSB levy would yield benefits for CHD mortality and inequalities. Brexit negotiations should deliver a fiscal and regulatory environment which promotes population health.

Background Valvular heart disease (VHD) is expected to become more common as the population ages. However, current estimates of its natural history and prevalence are based on historical studies with potential sources of bias. We conducted a cross-sectional analysis of the clinical and epidemiological characteristics of VHD identified at recruitment of a large cohort of older people. Methods and Results We enrolled 2500 individuals aged ≥65 years from a primary care population and screened for undiagnosed VHD using transthoracic echocardiography. Newly identified (predominantly mild) VHD was detected in 51% of participants. The most common abnormalities were aortic sclerosis (34%), mitral regurgitation (22%), and aortic regurgitation (15%). Aortic stenosis was present in 1.3%. The likelihood of undiagnosed VHD was 2-fold higher in the two most deprived socioeconomic quintiles than in the most affluent quintile, and 3-fold higher in individuals with atrial fibrillation. Clinically significant (moderate or severe) undiagnosed VHD was identified in 6.4%. In addition, 4.9% of the cohort had pre-existing VHD (a total prevalence of 11.3%). Projecting these findings using population data, we estimate that the prevalence of clinically significant VHD will double before 2050. Conclusions Previously undetected VHD affects 1 in 2 of the elderly population and is more common in lower socioeconomic classes. These unique data demonstrate the contemporary clinical and epidemiological characteristics of VHD in a large population-based cohort of older people and confirm the scale of the emerging epidemic of VHD, with widespread implications for clinicians and healthcare resources.