The George Institute for Global Health

Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases.

Background Canagliflozin is a sodium-glucose cotransporter 2 inhibitor that reduces glycemia as well as blood pressure, body weight, and albuminuria in people with diabetes. We report the effects of treatment with canagliflozin on cardiovascular, renal, and safety outcomes. Methods The CANVAS Program integrated data from two trials involving a total of 10,142 participants with type 2 diabetes and high cardiovascular risk. Participants in each trial were randomly assigned to receive canagliflozin or placebo and were followed for a mean of 188.2 weeks. The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Results The mean age of the participants was 63.3 years, 35.8% were women, the mean duration of diabetes was 13.5 years, and 65.6% had a history of cardiovascular disease. The rate of the primary outcome was lower with canagliflozin than with placebo (occurring in 26.9 vs. 31.5 participants per 1000 patient-years; hazard ratio, 0.86; 95% confidence interval [CI], 0.75 to 0.97; P<0.001 for noninferiority; P=0.02 for superiority). Although on the basis of the prespecified hypothesis testing sequence the renal outcomes are not viewed as statistically significant, the results showed a possible benefit of canagliflozin with respect to the progression of albuminuria (hazard ratio, 0.73; 95% CI, 0.67 to 0.79) and the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate, the need for renal-replacement therapy, or death from renal causes (hazard ratio, 0.60; 95% CI, 0.47 to 0.77). Adverse reactions were consistent with the previously reported risks associated with canagliflozin except for an increased risk of amputation (6.3 vs. 3.4 participants per 1000 patient-years; hazard ratio, 1.97; 95% CI, 1.41 to 2.75); amputations were primarily at the level of the toe or metatarsal. Conclusions In two trials involving patients with type 2 diabetes and an elevated risk of cardiovascular disease, patients treated with canagliflozin had a lower risk of cardiovascular events than those who received placebo but a greater risk of amputation, primarily at the level of the toe or metatarsal. (Funded by Janssen Research and Development; CANVAS and CANVAS-R ClinicalTrials.gov numbers, NCT01032629 and NCT01989754 , respectively.).

Importance: Elevated systolic blood (SBP) pressure is a leading global health risk. Quantifying the levels of SBP is important to guide prevention policies and interventions. Objective: To estimate the association between SBP of at least 110 to 115 mm Hg and SBP of 140 mm Hg or higher and the burden of different causes of death and disability by age and sex for 195 countries and territories, 1990-2015. Design: A comparative risk assessment of health loss related to SBP. Estimated distribution of SBP was based on 844 studies from 154 countries (published 1980-2015) of 8.69 million participants. Spatiotemporal Gaussian process regression was used to generate estimates of mean SBP and adjusted variance for each age, sex, country, and year. Diseases with sufficient evidence for a causal relationship with high SBP (eg, ischemic heart disease, ischemic stroke, and hemorrhagic stroke) were included in the primary analysis. Main Outcomes and Measures: Mean SBP level, cause-specific deaths, and health burden related to SBP (≥110-115 mm Hg and also ≥140 mm Hg) by age, sex, country, and year. Results: Between 1990-2015, the rate of SBP of at least 110 to 115 mm Hg increased from 73 119 (95% uncertainty interval [UI], 67 949-78 241) to 81 373 (95% UI, 76 814-85 770) per 100 000, and SBP of 140 mm Hg or higher increased from 17 307 (95% UI, 17 117-17 492) to 20 526 (95% UI, 20 283-20 746) per 100 000. The estimated annual death rate per 100 000 associated with SBP of at least 110 to 115 mm Hg increased from 135.6 (95% UI, 122.4-148.1) to 145.2 (95% UI 130.3-159.9) and the rate for SBP of 140 mm Hg or higher increased from 97.9 (95% UI, 87.5-108.1) to 106.3 (95% UI, 94.6-118.1). For loss of DALYs associated with systolic blood pressure of 140 mm Hg or higher, the loss increased from 95.9 million (95% uncertainty interval [UI], 87.0-104.9 million) to 143.0 million (95% UI, 130.2-157.0 million) [corrected], and for SBP of 140 mm Hg or higher, the loss increased from 5.2 million (95% UI, 4.6-5.7 million) to 7.8 million (95% UI, 7.0-8.7 million). The largest numbers of SBP-related deaths were caused by ischemic heart disease (4.9 million [95% UI, 4.0-5.7 million]; 54.5%), hemorrhagic stroke (2.0 million [95% UI, 1.6-2.3 million]; 58.3%), and ischemic stroke (1.5 million [95% UI, 1.2-1.8 million]; 50.0%). In 2015, China, India, Russia, Indonesia, and the United States accounted for more than half of the global DALYs related to SBP of at least 110 to 115 mm Hg. Conclusions and Relevance: In international surveys, although there is uncertainty in some estimates, the rate of elevated SBP (≥110-115 and ≥140 mm Hg) increased substantially between 1990 and 2015, and DALYs and deaths associated with elevated SBP also increased. Projections based on this sample suggest that in 2015, an estimated 3.5 billion adults had SBP of at least 110 to 115 mm Hg and 874 million adults had SBP of 140 mm Hg or higher.

Jena Univ Hosp, Jena, Germany

BACKGROUND: Large-scale and contemporary population-based studies of heart failure incidence are needed to inform resource planning and research prioritisation but current evidence is scarce. We aimed to assess temporal trends in incidence and prevalence of heart failure in a large general population cohort from the UK, between 2002 and 2014. METHODS: For this population-based study, we used linked primary and secondary electronic health records of 4 million individuals from the Clinical Practice Research Datalink (CPRD), a cohort that is representative of the UK population in terms of age and sex. Eligible patients were aged 16 years and older, had contributed data between Jan 1, 2002, and Dec 31, 2014, had an acceptable record according to CPRD quality control, were approved for CPRD and Hospital Episodes Statistics linkage, and were registered with their general practice for at least 12 months. For patients with incident heart failure, we extracted the most recent measurement of baseline characteristics (within 2 years of diagnosis) from electronic health records, as well as information about comorbidities, socioeconomic status, ethnicity, and region. We calculated standardised rates by applying direct age and sex standardisation to the 2013 European Standard Population, and we inferred crude rates by applying year-specific, age-specific, and sex-specific incidence to UK census mid-year population estimates. We assumed no heart failure for patients aged 15 years or younger and report total incidence and prevalence for all ages (>0 years). FINDINGS: From 2002 to 2014, heart failure incidence (standardised by age and sex) decreased, similarly for men and women, by 7% (from 358 to 332 per 100 000 person-years; adjusted incidence ratio 0·93, 95% CI 0·91-0·94). However, the estimated absolute number of individuals with newly diagnosed heart failure in the UK increased by 12% (from 170 727 in 2002 to 190 798 in 2014), largely due to an increase in population size and age. The estimated absolute number of prevalent heart failure cases in the UK increased even more, by 23% (from 750 127 to 920 616). Over the study period, patient age and multi-morbidity at first presentation of heart failure increased (mean age 76·5 years [SD 12·0] to 77·0 years [12·9], adjusted difference 0·79 years, 95% CI 0·37-1·20; mean number of comorbidities 3·4 [SD 1·9] vs 5·4 [2·5]; adjusted difference 2·0, 95% CI 1·9-2·1). Socioeconomically deprived individuals were more likely to develop heart failure than were affluent individuals (incidence rate ratio 1·61, 95% CI 1·58-1·64), and did so earlier in life than those from the most affluent group (adjusted difference -3·51 years, 95% CI -3·77 to -3·25). From 2002 to 2014, the socioeconomic gradient in age at first presentation with heart failure widened. Socioeconomically deprived individuals also had more comorbidities, despite their younger age. INTERPRETATION: Despite a moderate decline in standardised incidence of heart failure, the burden of heart failure in the UK is increasing, and is now similar to the four most common causes of cancer combined. The observed socioeconomic disparities in disease incidence and age at onset within the same nation point to a potentially preventable nature of heart failure that still needs to be tackled. FUNDING: British Heart Foundation and National Institute for Health Research.

Background Chronic obstructive pulmonary disease (COPD) is an increasingly important cause of morbidity, disability, and mortality worldwide. We aimed to estimate global, regional, and national COPD prevalence and risk factors to guide policy and population interventions. Methods For this systematic review and modelling study, we searched MEDLINE, Embase, Global Health, and CINAHL, for population-based studies on COPD prevalence published between Jan 1, 1990, and Dec 31, 2019. We included data reported using the two main case definitions: the Global Initiative for Chronic Obstructive Lung Disease fixed ratio (GOLD; FEV 1 /FVC<0·7) and the lower limit of normal (LLN; FEV 1 /FVC Findings We identified 162 articles reporting population-based studies conducted across 260 sites in 65 countries. In 2019, the global prevalence of COPD among people aged 30–79 years was 10·3% (95% CI 8·2–12·8) using the GOLD case definition, which translates to 391·9 million people (95% CI 312·6–487·9), and 7·6% (5·8–10·1) using the LLN definition, which translates to 292·0 million people (219·8–385·6). Using the GOLD definition, we estimated that 391·9 million (95% CI 312·6–487·9) people aged 30–79 years had COPD worldwide in 2019, with most (315·5 million [246·7–399·6]; 80·5%) living in LMICs. The overall prevalence of GOLD-COPD among people aged 30–79 years was the highest in the Western Pacific region (11·7% [95% CI 9·3–14·6]) and lowest in the region of the Americas (6·8% [95% CI 5·6–8·2]). Globally, male sex (OR 2·1 [95% CI 1·8–2·3]), smoking (current smoker 3·2 [2·5–4·0]; ever smoker 2·3 [2·0–2·5]), body-mass index of less than 18·5 kg/m 2 (2·2 [1·7–2·7]), biomass exposure (1·4 [1·2–1·7]), and occupational exposure to dust or smoke (1·4 [1·3–1·6]) were all substantial risk factors for COPD. Interpretation With more than three-quarters of global COPD cases in LMICs, tackling this chronic condition is a major and increasing challenge for health systems in these settings. In the absence of targeted population-wide efforts and health system reforms in these settings, many of which are under-resourced, achieving a substantial reduction in the burden of COPD globally might remain a difficult task. Funding National Institute for Health Research and Health Data Research UK.

BACKGROUND: Peripheral artery disease is a major cardiovascular disease that affected 202 million people worldwide in 2010. In the past decade, new epidemiological data on peripheral artery disease have emerged, enabling us to provide updated estimates of the prevalence and risk factors for peripheral artery disease globally and regionally and, for the first time, nationally. METHODS: For this systematic review and analysis, we did a comprehensive literature search for studies reporting on the prevalence of peripheral artery disease in the general population that were published between Jan 1, 2011, and April 30, 2019, in PubMed, MEDLINE, Embase, the Global Health database, CINAHL, the Global Health Library, the Allied and Complementary Medicine Database, and ProQuest Dissertations and Theses Global. We also included the Global Peripheral Artery Disease Study of 2013 and the China Peripheral Artery Disease Study as sources. Peripheral artery disease had to be defined as an ankle-brachial index lower than or equal to 0·90. With a purpose-built data collection form, data on study characteristics, sample characteristics, prevalence, and risk factors were abstracted from all the included studies identified from the sources. Age-specific and sex-specific prevalence of peripheral artery disease was estimated in both high-income countries (HICs) and low-income and middle-income countries (LMICs). We also did random-effects meta-analyses to pool the odds ratios of 30 risk factors for peripheral artery disease in HICs and LMICs. UN population data were used to generate the number of people affected by the disease in 2015. Finally, we derived the regional and national numbers of people with peripheral artery disease on the basis of a risk factor-based model. FINDINGS: We included 118 articles for systematic review and analysis. The prevalence of peripheral artery disease increased consistently with age. At younger ages, prevalence was slightly higher in LMICs than HICs (4·32%, 95% CI 3·01-6·29, vs 3·54%, 1·17-10·24, at 40-44 years), but the increase with age was greater in HICs than LMICs, leading to a higher prevalence in HICs than LMICs at older ages (21·24%, 15·22-28·90, vs 12·04%, 8·67-16·60, at 80-84 years). In HICs, prevalence was slightly higher in women than in men up to age 75 years (eg, 7·81%, 3·97-14·77, vs 6·60%, 3·74-11·38, at 55-59 years), whereas in LMICs little difference was found between women and men (eg, 6·40%, 5·06-8·05, vs 6·37%, 4·74-8·49, at 55-59 years). Overall, the global prevalence of peripheral artery disease in people aged 25 years and older was 5·56%, 3·79-8·55, and the prevalence estimate was higher in HICs than that in LMICs (7·37%, 4·35-13·66, vs 5·09%, 3·64-7·24). Smoking, diabetes, hypertension, and hypercholesterolaemia were major risk factors for peripheral artery disease. Globally, a total of 236·62 million people aged 25 years and older were living with peripheral artery disease in 2015, among whom 72·91% were in LMICs. The Western Pacific Region had the most peripheral artery disease cases (74·08 million), whereas the Eastern Mediterranean Region had the least (14·67 million). More than two thirds of the global peripheral artery disease cases were concentrated in 15 individual countries in 2015. INTERPRETATION: Peripheral artery disease continues to become an increasingly serious public health problem, especially in LMICs. With the demographic trend towards ageing and projected rise in important risk factors, a larger burden of peripheral artery disease is to be expected in the foreseeable future. FUNDING: None.

The aim of this study was to present and compare the content of (inter)national clinical guidelines for the management of low back pain. To rationalise the management of low back pain, evidence-based clinical guidelines have been issued in many countries. Given that the available scientific evidence is the same, irrespective of the country, one would expect these guidelines to include more or less similar recommendations regarding diagnosis and treatment. We updated a previous review that included clinical guidelines published up to and including the year 2000. Guidelines were included that met the following criteria: the target group consisted mainly of primary health care professionals, and the guideline was published in English, German, Finnish, Spanish, Norwegian, or Dutch. Only one guideline per country was included: the one most recently published. This updated review includes national clinical guidelines from 13 countries and 2 international clinical guidelines from Europe published from 2000 until 2008. The content of the guidelines appeared to be quite similar regarding the diagnostic classification (diagnostic triage) and the use of diagnostic and therapeutic interventions. Consistent features for acute low back pain were the early and gradual activation of patients, the discouragement of prescribed bed rest and the recognition of psychosocial factors as risk factors for chronicity. For chronic low back pain, consistent features included supervised exercises, cognitive behavioural therapy and multidisciplinary treatment. However, there are some discrepancies for recommendations regarding spinal manipulation and drug treatment for acute and chronic low back pain. The comparison of international clinical guidelines for the management of low back pain showed that diagnostic and therapeutic recommendations are generally similar. There are also some differences which may be due to a lack of strong evidence regarding these topics or due to differences in local health care systems. The implementation of these clinical guidelines remains a challenge for clinical practice and research.

OBJECTIVES: To determine the effects of exercise on falls prevention in older people and establish whether particular trial characteristics or components of exercise programs are associated with larger reductions in falls. DESIGN: Systematic review with meta-analysis. Randomized controlled trials that compared fall rates in older people who undertook exercise programs with fall rates in those who did not exercise were included. SETTING: Older people. PARTICIPANTS: General community and residential care. MEASUREMENTS: Fall rates. RESULTS: The pooled estimate of the effect of exercise was that it reduced the rate of falling by 17% (44 trials with 9,603 participants, rate ratio (RR)=0.83, 95% confidence interval (CI)=0.75-0.91, P<.001, I(2)=62%). The greatest relative effects of exercise on fall rates (RR=0.58, 95% CI=0.48-0.69, 68% of between-study variability explained) were seen in programs that included a combination of a higher total dose of exercise (>50 hours over the trial period) and challenging balance exercises (exercises conducted while standing in which people aimed to stand with their feet closer together or on one leg, minimize use of their hands to assist, and practice controlled movements of the center of mass) and did not include a walking program. CONCLUSION: Exercise can prevent falls in older people. Greater relative effects are seen in programs that include exercises that challenge balance, use a higher dose of exercise, and do not include a walking program. Service providers can use these findings to design and implement exercise programs for falls prevention.

BACKGROUND: Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease. METHODS: We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose-response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12·5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5·6 years [5th-95th percentile 1·04-13·5]) from 71 011 participants from 37 studies. FINDINGS: In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5·4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around or below 100 g per week. Alcohol consumption was roughly linearly associated with a higher risk of stroke (HR per 100 g per week higher consumption 1·14, 95% CI, 1·10-1·17), coronary disease excluding myocardial infarction (1·06, 1·00-1·11), heart failure (1·09, 1·03-1·15), fatal hypertensive disease (1·24, 1·15-1·33); and fatal aortic aneurysm (1·15, 1·03-1·28). By contrast, increased alcohol consumption was log-linearly associated with a lower risk of myocardial infarction (HR 0·94, 0·91-0·97). In comparison to those who reported drinking >0-≤100 g per week, those who reported drinking >100-≤200 g per week, >200-≤350 g per week, or >350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1-2 years, or 4-5 years, respectively. INTERPRETATION: In current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week. For cardiovascular disease subtypes other than myocardial infarction, there were no clear risk thresholds below which lower alcohol consumption stopped being associated with lower disease risk. These data support limits for alcohol consumption that are lower than those recommended in most current guidelines. FUNDING: UK Medical Research Council, British Heart Foundation, National Institute for Health Research, European Union Framework 7, and European Research Council.

The October 2020 Global TB report reviews TB control strategies and United Nations (UN) targets set in the political declaration at the September 2018 UN General Assembly high-level meeting on TB held in New York. Progress in TB care and prevention has been very slow. In 2019, TB remained the most common cause of death from a single infectious pathogen. Globally, an estimated 10.0 million people developed TB disease in 2019, and there were an estimated 1.2 million TB deaths among HIV-negative people and an additional 208, 000 deaths among people living with HIV. Adults accounted for 88% and children for 12% of people with TB. The WHO regions of South-East Asia (44%), Africa (25%), and the Western Pacific (18%) had the most people with TB. Eight countries accounted for two thirds of the global total: India (26%), Indonesia (8.5%), China (8.4%), the Philippines (6.0%), Pakistan (5.7%), Nigeria (4.4%), Bangladesh (3.6%) and South Africa (3.6%). Only 30% of the 3.5 million five-year target for children treated for TB was met. Major advances have been development of new all oral regimens for MDRTB and new regimens for preventive therapy. In 2020, the COVID-19 pandemic dislodged TB from the top infectious disease cause of mortality globally. Notably, global TB control efforts were not on track even before the advent of the COVID-19 pandemic. Many challenges remain to improve sub-optimal TB treatment and prevention services. Tuberculosis screening and diagnostic test services need to be ramped up. The major drivers of TB remain undernutrition, poverty, diabetes, tobacco smoking, and household air pollution and these need be addressed to achieve the WHO 2035 TB care and prevention targets. National programs need to include interventions for post-tuberculosis holistic wellbeing. From first detection of COVID-19 global coordination and political will with huge financial investments have led to the development of effective vaccines against SARS-CoV2 infection. The world now needs to similarly focus on development of new vaccines for TB utilizing new technological methods.

With Black Patients (African Ancestry) 4. How is Hypertension Defined? 5. How is Hypertension Classified? 6. Causes of Hypertension 7. Making the Diagnosis of Hypertension 8. Evaluating the Patient 9. Physical Examination 10.Tests 11.Goals of Treating Hypertension 12. Nonpharmacologic Treatment of Hypertension 13.Drug treatment for Hypertension 14. Brief Comments on Drug Classes 15.Treatment-Resistant

BACKGROUND: Estimation of the epidemiological burden of carotid atherosclerosis can serve as a basis for prevention and management of cardiovascular disease. We aimed to provide the first estimation on the prevalence, number of cases, and risk factors for carotid atherosclerosis in the general population globally and regionally. METHODS: In this systematic review, meta-analysis, and modelling study, we searched PubMed, MEDLINE, Embase, Global Health, and China National Knowledge Infrastructure for articles published from database inception until May 7, 2019, with no language restrictions, for population-based studies that quantified prevalence of carotid atherosclerosis by means of increased carotid intima-media thickness, carotid plaque, and carotid stenosis. Studies were eligible if they included bilaterally scanned carotid arteries using ultrasonography and defined increased carotid intima-media thickness as a thickness of 1·0 mm or more, carotid plaque as a focal carotid intima-media thickness of 1·5 mm or more encroaching into the lumen or at least 0·5 mm or 50% compared with the surrounding carotid intima-media thickness values, and carotid stenosis as 50% or more stenosis. Studies were excluded if the sample was not representative of the general population. We also included studies identified in our previous systematic review and meta-analysis of the prevalence of carotid atherosclerosis in China. We estimated age-specific and sex-specific prevalences of increased carotid intima-media thickness, carotid plaque, and carotid stenosis. We used UN population data to generate the number of people affected in 2000, 2015, and 2020. We did random-effects meta-analyses to assess the effects of risk factors for increased carotid intima-media thickness and carotid plaque. We derived regional numbers of people living with increased carotid intima-media thickness and carotid plaque in 2015 using a risk factors-based model by WHO region. All analyses were done in populations aged 30-79 years due to availability of data. This systematic review and meta-analysis is registered online on PROSPERO, CRD42019134709. FINDINGS: We identified 8632 articles through our database search, of which 515 were eligible for full-text review, including 37 articles from our previous study, and 59 articles were eligible for inclusion in our systematic review and meta-analysis. Overall, in people aged 30-79 years in 2020, the global prevalence of increased carotid intima-media thickness is estimated to be 27·6% (95% CI 16·9-41·3), equivalent to 1066·70 million affected people and a percentage change of 57·46% from 2000; of carotid plaque is estimated to be 21·1% (13·2-31·5), equivalent to 815·76 million affected people and a percentage change of 58·97% from 2000; and carotid stenosis is estimated to be 1·5% (1·1-2·1), equivalent to 57·79 million affected people and a percentage change of 59·13% from 2000. The prevalence of increased carotid intima-media thickness, carotid plaque, and carotid stenosis increased consistently with age and was higher in men than in women. Current smoking, diabetes, and hypertension were common risk factors for increased carotid intima-media thickness and carotid plaque. In 2015, the Western Pacific region had the largest share of global cases of increased carotid intima-media thickness (317·62 million [33·36%] of 952·13 million affected people) and carotid plaque (240·77 million [33·20%] of 725·25 million), whereas the African region had the smallest share of cases of increased carotid intima-media thickness (59·08 million [6·21%]) and the Eastern Mediterranean region had the smallest share of carotid plaque cases (44·59 million [6·15%]). INTERPRETATION: A substantial global burden of carotid atherosclerosis exists. Effective strategies are needed for primary prevention and management of carotid atherosclerosis. High-quality epidemiological investigations on carotid atherosclerosis are needed to better address the global burden of carotid atherosclerosis at finer levels. FUNDING: None.

IMPORTANCE: Lowering blood pressure (BP) is widely used to reduce vascular risk in individuals with diabetes. OBJECTIVE: To determine the associations between BP-lowering treatment and vascular disease in type 2 diabetes. DATA SOURCES AND STUDY SELECTION: We searched MEDLINE for large-scale randomized controlled trials of BP-lowering treatment including patients with diabetes, published between January 1966 and October 2014. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted study characteristics and vascular outcome data. Estimates were stratified by baseline BP and achieved BP, and pooled using fixed-effects meta-analysis. MAIN OUTCOMES AND MEASURES: All-cause mortality, cardiovascular events, coronary heart disease events, stroke, heart failure, retinopathy, new or worsening albuminuria, and renal failure. RESULTS: Forty trials judged to be of low risk of bias (100,354 participants) were included. Each 10-mm Hg lower systolic BP was associated with a significantly lower risk of mortality (relative risk [RR], 0.87; 95% CI, 0.78-0.96); absolute risk reduction (ARR) in events per 1000 patient-years (3.16; 95% CI, 0.90-5.22), cardiovascular events (RR, 0.89 [95% CI, 0.83-0.95]; ARR, 3.90 [95% CI, 1.57-6.06]), coronary heart disease (RR, 0.88 [95% CI, 0.80-0.98]; ARR, 1.81 [95% CI, 0.35-3.11]), stroke (RR, 0.73 [95% CI, 0.64-0.83]; ARR, 4.06 [95% CI, 2.53-5.40]), albuminuria (RR, 0.83 [95% CI, 0.79-0.87]; ARR, 9.33 [95% CI, 7.13-11.37]), and retinopathy (RR, 0.87 [95% CI, 0.76-0.99]; ARR, 2.23 [95% CI, 0.15-4.04]). When trials were stratified by mean baseline systolic BP at greater than or less than 140 mm Hg, RRs for outcomes other than stroke, retinopathy, and renal failure were lower in studies with greater baseline systolic BP (P interaction <0.1). The associations between BP-lowering treatments and outcomes were not significantly different, irrespective of drug class, except for stroke and heart failure. Estimates were similar when all trials, regardless of risk of bias, were included. CONCLUSIONS AND RELEVANCE: Among patients with type 2 diabetes, BP lowering was associated with improved mortality and other clinical outcomes with lower RRs observed among those with baseline BP of 140 mm Hg and greater. These findings support the use of medications for BP lowering in these patients.

This systematic review update includes 54 randomised controlled trials and confirms that exercise as a single intervention can prevent falls (pooled rate ratio 0.84, 95% CI 0.77-0.91). Meta-regression revealed programs that included balance training, contained a higher dose of exercise and did not include walking training to have the greatest effect on reducing falls. We therefore recommend that exercise for falls prevention should provide a moderate or high challenge to balance and be undertaken for at least 2 hours per week on an ongoing basis. Additionally, we recommend that: falls prevention exercise should target both the general community and those at high risk for falls; exercise may be undertaken in a group or home-based setting; strength and walking training may be included in addition to balance training but high risk individuals should not be prescribed brisk walking programs; and other health-related risk factors should also be addressed.

BACKGROUND: For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions. METHODS: The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310 000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120 000 sources were used for estimation of disease and injury burden and 59 000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010-23 period and presented as counts (to three significant figures) and age-standardised rates per 100 000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2·5th and 97·5th percentile ordered values from a 250-draw distribution. FINDINGS: Total numbers of global DALYs grew 6·1% (95% UI 4·0-8·1), from 2·64 billion (2·46-2·86) in 2010 to 2·80 billion (2·57-3·08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12·6% (11·0-14·1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1·45 billion (1·31-1·61) global DALYs in 2010, increasing to 1·80 billion (1·63-2·03) in 2023, alongside a concurrent 4·1% (1·9-6·3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176-209] DALYs), stroke (157 million [141-172]), and diabetes (90·2 million [75·2-107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62·8% [34·0-107·5]), depressive disorders (26·3% [11·6-42·9]), and diabetes (14·9% [7·5-25·6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837-917) in 2010 to 681 million (642-736) in 2023, and a 25·8% (22·6-28·7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49·1% (32·7-61·0) for diarrhoeal diseases, 42·9% (38·0-48·0) for HIV/AIDS, and 42·2% (23·6-56·6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16·5% (10·6-22·0) and 24·8% (7·4-36·7), respectively. Injury-related age-standardised DALY rates decreased by 15·6% (10·7-19·8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1·27 billion [1·18-1·38]) of the roughly 2·80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation-with high SBP accounting for 8·4% (6·9-10·0) of total DALYs. Of the three overarching level 1 GBD risk factor categories-behavioural, metabolic, and environmental and occupational-risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30·7% (24·8-37·3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6·7% (2·0-11·0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023-eg, declining by 54·4% (38·7-65·3) for unsafe sanitation, 50·5% (33·3-63·1) for unsafe water source, and 45·2% (25·6-72·0) for no access to handwashing facility, and by 44·9% (37·3-53·5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10·5% [0·1 to 20·9]), drug use (8·4% [2·6 to 15·3]), and high FPG (6·2% [-2·7 to 15·6]; non-significant). INTERPRETATION: Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors-eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG-including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic-the complex interaction of multiple health risks, social determinants, and systemic challenges-will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity. FUNDING: Gates Foundation and Bloomberg Philanthropies.

Importance: Reliable estimates of the prevalence of childhood hypertension serve as the basis for adequate prevention and treatment. However, the prevalence of childhood hypertension has rarely been synthesized at the global level. Objective: To conduct a systematic review and meta-analysis to assess the prevalence of hypertension in the general pediatric population. Data Sources: PubMed, MEDLINE, Embase, Global Health, and Global Health Library were searched from inception until June 2018, using search terms related to hypertension (hypertension OR high blood pressure OR elevated blood pressure), children (children OR adolescents), and prevalence (prevalence OR epidemiology). Study Selection: Studies that were conducted in the general pediatric population and quantified the prevalence of childhood hypertension were eligible. Included studies had blood pressure measurements from at least 3 separate occasions. Data Extraction and Synthesis: Two authors independently extracted data. Random-effects meta-analysis was used to derive the pooled prevalence. Variations in the prevalence estimates in different subgroups, including age group, sex, setting, device, investigation period, BMI group, World Health Organization region and World Bank region, were examined by subgroup meta-analysis. Meta-regression was used to establish the age-specific prevalence of childhood hypertension and to assess its secular trend. Main Outcomes and Measures: Prevalence of childhood hypertension overall and by subgroup. Results: A total of 47 articles were included in the meta-analysis. The pooled prevalence was 4.00% (95% CI, 3.29%-4.78%) for hypertension, 9.67% (95% CI, 7.26%-12.38%) for prehypertension, 4.00% (95% CI, 2.10%-6.48%) for stage 1 hypertension, and 0.95% (95% CI, 0.48%-1.57%) for stage 2 hypertension in children 19 years and younger. In subgroup meta-analyses, the prevalence of childhood hypertension was higher when measured by aneroid sphygmomanometer (7.23% vs 4.59% by mercury sphygmomanometer vs 2.94% by oscillometric sphygmomanometer) and among overweight and obese children (15.27% and 4.99% vs 1.90% among normal-weight children). A trend of increasing prevalence of childhood hypertension was observed during the past 2 decades, with a relative increasing rate of 75% to 79% from 2000 to 2015. In 2015, the prevalence of hypertension ranged from 4.32% (95% CI, 2.79%-6.63%) among children aged 6 years to 3.28% (95% CI, 2.25%-4.77%) among those aged 19 years and peaked at 7.89% (95% CI, 5.75%-10.75%) among those aged 14 years. Conclusions and Relevance: This study provides a global estimation of childhood hypertension prevalence based on blood pressure measurements in at least 3 separate visits. More high-quality epidemiologic investigations on childhood hypertension are still needed.

OBJECTIVE: Type 2 diabetes confers a greater excess risk of cardiovascular disease in women than in men. Diabetes is also a risk factor for dementia, but whether the association is similar in women and men remains unknown. We performed a meta-analysis of unpublished data to estimate the sex-specific relationship between women and men with diabetes with incident dementia. RESEARCH DESIGN AND METHODS: A systematic search identified studies published prior to November 2014 that had reported on the prospective association between diabetes and dementia. Study authors contributed unpublished sex-specific relative risks (RRs) and 95% CIs on the association between diabetes and all dementia and its subtypes. Sex-specific RRs and the women-to-men ratio of RRs (RRRs) were pooled using random-effects meta-analyses. RESULTS: Study-level data from 14 studies, 2,310,330 individuals, and 102,174 dementia case patients were included. In multiple-adjusted analyses, diabetes was associated with a 60% increased risk of any dementia in both sexes (women: pooled RR 1.62 [95% CI 1.45-1.80]; men: pooled RR 1.58 [95% CI 1.38-1.81]). The diabetes-associated RRs for vascular dementia were 2.34 (95% CI 1.86-2.94) in women and 1.73 (95% CI 1.61-1.85) in men, and for nonvascular dementia, the RRs were 1.53 (95% CI 1.35-1.73) in women and 1.49 (95% CI 1.31-1.69) in men. Overall, women with diabetes had a 19% greater risk for the development of vascular dementia than men (multiple-adjusted RRR 1.19 [95% CI 1.08-1.30]; P < 0.001). CONCLUSIONS: Individuals with type 2 diabetes are at ∼60% greater risk for the development of dementia compared with those without diabetes. For vascular dementia, but not for nonvascular dementia, the additional risk is greater in women.

Document analysis is one of the most commonly used and powerful methods in health policy research. While existing qualitative research manuals offer direction for conducting document analysis, there has been little specific discussion about how to use this method to understand and analyse health policy. Drawing on guidance from other disciplines and our own research experience, we present a systematic approach for document analysis in health policy research called the READ approach: (1) ready your materials, (2) extract data, (3) analyse data and (4) distil your findings. We provide practical advice on each step, with consideration of epistemological and theoretical issues such as the socially constructed nature of documents and their role in modern bureaucracies. We provide examples of document analysis from two case studies from our work in Pakistan and Niger in which documents provided critical insight and advanced empirical and theoretical understanding of a health policy issue. Coding tools for each case study are included as Supplementary Files to inspire and guide future research. These case studies illustrate the value of rigorous document analysis to understand policy content and processes and discourse around policy, in ways that are either not possible using other methods, or greatly enrich other methods such as in-depth interviews and observation. Given the central nature of documents to health policy research and importance of reading them critically, the READ approach provides practical guidance on gaining the most out of documents and ensuring rigour in document analysis.

BACKGROUND: Globally, a growing number of children and adolescents are left behind when parents migrate. We investigated the effect of parental migration on the health of left behind-children and adolescents in low-income and middle-income countries (LMICs). METHODS: For this systematic review and meta-analysis we searched MEDLINE, Embase, CINAHL, the Cochrane Library, Web of Science, PsychINFO, Global Index Medicus, Scopus, and Popline from inception to April 27, 2017, without language restrictions, for observational studies investigating the effects of parental migration on nutrition, mental health, unintentional injuries, infectious disease, substance use, unprotected sex, early pregnancy, and abuse in left-behind children (aged 0-19 years) in LMICs. We excluded studies in which less than 50% of participants were aged 0-19 years, the mean or median age of participants was more than 19 years, fewer than 50% of parents had migrated for more than 6 months, or the mean or median duration of migration was less than 6 months. We screened studies using systematic review software and extracted summary estimates from published reports independently. The main outcomes were risk and prevalence of health outcomes, including nutrition (stunting, wasting, underweight, overweight and obesity, low birthweight, and anaemia), mental health (depressive disorder, anxiety disorder, conduct disorders, self-harm, and suicide), unintentional injuries, substance use, abuse, and infectious disease. We calculated pooled risk ratios (RRs) and standardised mean differences (SMDs) using random-effects models. This study is registered with PROSPERO, number CRD42017064871. FINDINGS: Our search identified 10 284 records, of which 111 studies were included for analysis, including a total of 264 967 children (n=106 167 left-behind children and adolescents; n=158 800 children and adolescents of non-migrant parents). 91 studies were done in China and focused on effects of internal labour migration. Compared with children of non-migrants, left-behind children had increased risk of depression and higher depression scores (RR 1·52 [95% CI 1·27-1·82]; SMD 0·16 [0·10-0·21]), anxiety (RR 1·85 [1·36-2·53]; SMD 0·18 [0·11-0·26]), suicidal ideation (RR 1·70 [1·28-2·26]), conduct disorder (SMD 0·16 [0·04-0·28]), substance use (RR 1·24 [1·00-1·52]), wasting (RR 1·13 [1·02-1·24]) and stunting (RR 1·12 [1·00-1·26]). No differences were identified between left-behind children and children of non-migrants for other nutrition outcomes, unintentional injury, abuse, or diarrhoea. No studies reported outcomes for other infectious diseases, self-harm, unprotected sex, or early pregnancy. Study quality varied across the included studies, with 43% of studies at high or unclear risk of bias across five or more domains. INTERPRETATION: Parental migration is detrimental to the health of left-behind children and adolescents, with no evidence of any benefit. Policy makers and health-care professionals need to take action to improve the health of these young people. FUNDING: Wellcome Trust.