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While racial/ethnic disparities in blood pressure control are documented, few interventions have successfully reduced these gaps. Under-prescribing, lack of treatment intensification, and suboptimal follow-up care are thought to be central contributors. Electronic health record (EHR) tools may help address these barriers and may be enhanced with behavioral science techniques.To evaluate the impact of a multicomponent behaviorally-informed EHR-based intervention on blood pressure control.Reducing Ethnic and racial Disparities by improving Undertreatment, Control, and Engagement in Blood Pressure management with health information technology (REDUCE-BP) (NCT05030467) is a two-arm cluster-randomized hybrid type 1 pragmatic trial in a large multi-ethnic health care system. Twenty-four clinics (350 primary care providers [PCPs] and10,000 eligible patients) are assigned to either multi-component EHR-based intervention or usual care. Intervention clinic PCPs will receive several EHR tools designed to reduce disparities delivered at different points, including a: (1) dashboard of all patients visible upon logging on to the EHR displaying blood pressure control by race/ethnicity compared to their PCP peers and (2) set of tools in an individual patient's chart containing decision support to encourage treatment intensification, ordering home blood pressure measurement, interventions to address health-related social needs, default text for note documentation, and enhanced patient education materials. The primary outcome is patient-level change in systolic blood pressure over 12 months between arms; secondary outcomes include changes in disparities and other clinical outcomes.REDUCE-BP will provide important insights into whether an EHR-based intervention designed using behavioral science can improve hypertension control and reduce disparities.

The triglyceride glucose (TyG) index is an easily accessible surrogate marker of insulin resistance, an important pathway in the development of type 2 diabetes and cardiovascular diseases. However, the association of the TyG index with cardiovascular diseases and mortality has mainly been investigated in Asia, with few data available from other regions of the world. We assessed the association of insulin resistance (as determined by the TyG index) with mortality and cardiovascular diseases in individuals from five continents at different levels of economic development, living in urban or rural areas. We also examined whether the associations differed according to the country's economical development.We used the TyG index as a surrogate measure for insulin resistance. Fasting triglycerides and fasting plasma glucose were measured at the baseline visit in 141 243 individuals aged 35-70 years from 22 countries in the Prospective Urban Rural Epidemiology (PURE) study. The TyG index was calculated as Ln (fasting triglycerides [mg/dL] x fasting plasma glucose [mg/dL]/2). We calculated hazard ratios (HRs) using a multivariable Cox frailty model with random effects to test the associations between the TyG index and risk of cardiovascular diseases and mortality. The primary outcome of this analysis was the composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, and non-fatal myocardial infarction, or stroke). Secondary outcomes were non-cardiovascular mortality, cardiovascular mortality, all myocardial infarctions, stroke, and incident diabetes. We also did subgroup analyses to examine the magnitude of associations between insulin resistance (ie, the TyG index) and outcome events according to the income level of the countries.During a median follow-up of 13·2 years (IQR 11·9-14·6), we recorded 6345 composite cardiovascular diseases events, 2030 cardiovascular deaths, 3038 cases of myocardial infarction, 3291 cases of stroke, and 5191 incident cases of type 2 diabetes. After adjusting for all other variables, the risk of developing cardiovascular diseases increased across tertiles of the baseline TyG index. Compared with the lowest tertile of the TyG index, the highest tertile (tertile 3) was associated with a greater incidence of the composite outcome (HR 1·21; 95% CI 1·13-1·30), myocardial infarction (1·24; 1·12-1·38), stroke (1·16; 1·05-1·28), and incident type 2 diabetes (1·99; 1·82-2·16). No significant association of the TyG index was seen with non-cardiovascular mortality. In low-income countries (LICs) and middle-income countries (MICs), the highest tertile of the TyG index was associated with increased hazards for the composite outcome (LICs: HR 1·31; 95% CI 1·12-1·54; MICs: 1·20; 1·11-1·31; pThe TyG index is significantly associated with future cardiovascular mortality, myocardial infarction, stroke, and type 2 diabetes, suggesting that insulin resistance plays a promoting role in the pathogenesis of cardiovascular and metabolic diseases. Potentially, the association between the TyG index and the higher risk of cardiovascular diseases and type 2 diabetes in LICs and MICs might be explained by an increased vulnerability of these populations to the presence of insulin resistance.Full funding sources are listed at the end of the paper (see Acknowledgments).

Rasha Khatib,1 Eric J Yeh,2 Nicole Glowacki,1 Catherine B McGuiness,3 Handing Xie,4 Rolin L Wade,4 Bethany A Kalich,5 Yi Li,6 Abdelhadi Rifai,7 Neal Sawlani8 1Academic Research and Strategic Partnership, Advocate Aurora Research Institute, Advocate Aurora Health, Downers Grove, IL, USA; 2Global Health Economics and Outcomes Research (HEOR), Amgen Inc, Thousand Oaks, CA, USA; 3Health Economics and Outcomes Research, Real-World Evidence, IQVIA, Wayne, PA, USA; 4IQVIA, Wayne, PA, USA; 5Amgen Inc, Thousand Oaks, CA, USA; 6R&D Solutions, IQVIA, Bloomington, IL, USA; 7Heart & Vascular Institute, Cheyenne Regional Medical Group, Cheyenne, WY, USA; 8Advocate Lutheran General Hospital, Park Ridge, IL, USACorrespondence: Rasha Khatib, Academic Research and Strategic Partnership, Advocate Aurora Research Institute, Advocate Aurora Health, 3075 Highland Parkway, Suite 600, Downers Grove, IL, 60515, USA, Tel +1 708.684.3691, Email rasha.alkhatib@aah.orgIntroduction: Clinical practice guidelines recommend initiating a high-intensity LLT and continued monitoring of low-density lipoprotein cholesterol (LDL-C) following acute coronary syndrome (ACS). We used real-world data to describe LLT utilization after discharge and 1-year adherence. The reduction in LDL-C was also evaluated.Methods: Data were extracted from electronic health records (EHRs) from 12 hospitals in a large community healthcare system in midwestern United States between 2013 and 2019. Data on eligible patients recently discharged with an ACS event were linked to pharmacy claims data to describe LLT fill rates and 1-year post-discharge adherence. Adherence was reported as the proportion of days covered ≥ 80%.Results: Of the 10,589 eligible patients, 49% filled a high-intensity statin at discharge and only 36% were adherent at 1 year. The mean (SD) age was 66.1± 13.3, 39.3% were females, 58.8% were Caucasian, and 53.0% had Medicare. There was a clear trend for greater fill rates at discharge among patients with higher LDL-C values than those with lower values (p< 0.01). Key predictors of high-intensity (versus medium-intensity) LLT use within 21 days after an ACS event included ACS type (odds ratio [OR] 0.59; 95% confidence interval [CI] 0.52– 0.67 for NSTEMI versus STEMI), age group (OR: 0.59; 95% CI: 0.48– 0.72 for > 75 years versus < 65 years), and statin use before index ACS event (OR: 1.56; 95% CI: 1.23– 1.88).Conclusion: This real-world study found that despite recommendations in clinical practice guidelines, high-intensity LLT fill rates at discharge and 1-year adherence to LLT remain suboptimal. Clinical characteristics, including ACS type and LDL-C values, were strong predictors of filling and adherence to guideline-recommended therapy. Age, sex, and race/ethnicity disparities were observed in discharge fill rates and 1-year adherence. These results highlight the need for continued efforts at the patient and provider levels to improve LLT adherence among ACS patients.Keywords: lipid-lowering therapy, high-intensity statin, acute coronary syndrome, real-world data, prescribing, adherence

Digital, Background Separate studies suggest that the risks from smoking might vary between high-income (HICs), middle-income (MICs), and low-income (LICs) countries, but this has not yet been systematically examined within a single study using standardised approaches. We examined the variations in risks from smoking across different country income groups and some of their potential reasons. Methods We analysed data from 134 909 participants from 21 countries followed up for a median of 11·3 years in the Prospective Urban Rural Epidemiology (PURE) cohort study; 9711 participants with myocardial infarction and 11 362 controls from 52 countries in the INTERHEART case-control study; and 11 580 participants with stroke and 11 331 controls from 32 countries in the INTERSTROKE case-control study. In PURE, all-cause mortality, major cardiovascular disease, cancers, respiratory diseases, and their composite were the primary outcomes for this analysis. Biochemical verification of urinary total nicotine equivalent was done in a substudy of 1000 participants in PURE. Findings In PURE, the adjusted hazard ratio (HR) for the composite outcome in current smokers (vs never smokers) was higher in HICs (HR 1·87, 95% CI 1·65–2·12) than in MICs (1·41, 1·34–1·49) and LICs (1·35, 1·25–1·46; interaction p, Funding Full funding sources are listed at the end of the paper (see Acknowledgments)., Ciencias Médicas y de la Salud

Guideline developers consider cost-effectiveness evidence in decision making to determine value for money. This consideration in the guideline development process can be informed either by formal and dedicated economic evaluations or by systematic reviews of existing studies. To inform the American Society of Hematology guideline on the diagnosis of venous thromboembolism (VTE), we conducted a systematic review focused on the cost-effectiveness of diagnostic strategies for VTE within the guideline scope. We systematically searched Medline (Ovid), Embase (Ovid), National Health Service Economic Evaluation Database, and the Cost-effectiveness Analysis Registry; summarized; and critically appraised the economic evidence on diagnostic strategies for VTE. We identified 49 studies that met our inclusion criteria, with 26 on pulmonary embolism (PE) and 24 on deep vein thrombosis (DVT). For the diagnosis of PE, strategies including d-dimer to exclude PE were cost-effective compared with strategies without d-dimer testing. The cost-effectiveness of computed tomography pulmonary angiogram (CTPA) in relation to ventilation-perfusion (V/Q) scan was inconclusive. CTPA or V/Q scan following ultrasound or d-dimer results could be cost-effective or even cost saving. For DVT, studies supporting strategies with d-dimer and/or ultrasound were cost-effective, supporting the recommendation that for patients at low (unlikely) VTE risk, using d-dimer as the initial test reduces the need for diagnostic imaging. Our systematic review informed the American Society of Hematology guideline recommendations about d-dimer, V/Q scan and CTPA for PE diagnosis, and d-dimer and ultrasound for DVT diagnosis.

Urbanization may influence physical activity (PA) levels, although little evidence is available for low- and middle- income countries where urbanization is occurring fastest. We evaluated associations between urbanization and total PA, as well as work-, leisure-, home-, and transport-specific PA, for 138,206 adults living in 698 communities across 22 countries within the Prospective Urban and Rural Epidemiology (PURE) study. The 1-week long-form International PA Questionnaire was administered at baseline (2003–2015). We used satellite-derived population density and impervious surface area estimates to quantify baseline urbanization levels for study communities, as well as change measures for 5- and 10-years prior to PA surveys. We used generalized linear mixed effects models to examine associations between urbanization measures and PA levels, controlling for individual, household and community factors. Higher community baseline levels of population density (− 12.4% per IQR, 95% CI − 16.0, − 8.7) and impervious surface area (− 29.2% per IQR, 95% CI − 37.5, − 19.7), as well as the rate of change in 5-year population density (− 17.2% per IQR, 95% CI − 25.7, − 7.7), were associated with lower total PA levels. Important differences in the associations between urbanization and PA were observed between PA domains, country-income levels, urban/rural status, and sex. These findings provide new information on the complex associations between urbanization and PA.

ImportanceProlonged symptoms following SARS-CoV-2 infection, or Long COVID, is common, but few prospective studies of Long COVID risk factors have been conducted.ObjectiveTo determine whether sociodemographic factors, lifestyle, or medical history preceding COVID-19 or characteristics of acute SARS-CoV-2 infection are associated with Long COVID.DesignCohort study with longitudinal assessment of symptoms before, during, and after SARS-CoV-2 infection, and cross-sectional assessment of Long COVID symptoms using data from the COVID-19 Citizen Science (CCS) study.SettingCCS is an online cohort study that began enrolling March 26, 2020. We included data collected between March 26, 2020, and May 18, 2022.ParticipantsAdult CCS participants who reported a positive SARS-CoV-2 test result (PCR, Antigen, or Antibody) more than 30 days prior to May 4, 2022, were surveyed.ExposuresAge, sex, race/ethnicity, education, employment, socioeconomic status/financial insecurity, self-reported medical history, vaccination status, time of infection (variant wave), number of acute symptoms, pre-COVID depression, anxiety, alcohol and drug use, sleep, exercise.Main OutcomePresence of at least 1 Long COVID symptom greater than 1 month after acute infection. Sensitivity analyses were performed considering only symptoms beyond 3 months and only severe symptoms.Results13,305 participants reported a SARS-CoV-2 positive test more than 30 days prior, 1480 (11.1% of eligible) responded to a survey about Long COVID symptoms, and 476 (32.2% of respondents) reported Long COVID symptoms (median 360 days after infection).Respondents’ mean age was 53 and 1017 (69%) were female. Common Long COVID symptoms included fatigue, reported by 230/476 (48.3%), shortness of breath (109, 22.9%), confusion/brain fog (108, 22.7%), headache (103, 21.6%), and altered taste or smell (98, 20.6%). In multivariable models, number of acute COVID-19 symptoms (OR 1.30 per symptom, 95%CI 1.20-1.40), lower socioeconomic status/financial insecurity (OR 1.62, 95%CI 1.02-2.63), pre-infection depression (OR 1.08, 95%CI 1.01-1.16), and earlier variants (OR 0.37 for Omicron compared to ancestral strain, 95%CI 0.15-0.90) were associated with Long COVID symptoms.Conclusions and RelevanceVariant wave, severity of acute infection, lower socioeconomic status and pre-existing depression are associated with Long COVID symptoms.Key PointsQuestionWhat are the patterns of symptoms and risk factors for Long COVID among SARS-CoV-2 infected individuals?FindingsPersistent symptoms were highly prevalent, especially fatigue, shortness of breath, headache, brain fog/confusion, and altered taste/smell, which persisted beyond 1 year among 56% of participants with symptoms; a minority of participants reported severe Long COVID symptoms. Number of acute symptoms during acute SARS-CoV-2 infection, financial insecurity, pre-existing depression, and infection with earlier variants are associated with prevalent Long COVID symptoms independent of vaccination, medical history, and other factors.MeaningSeverity of acute infection, SARS-CoV-2 variant, and financial insecurity and depression are associated with Long COVID symptoms.

Several medications have been suspected to contribute to the etiology of inflammatory bowel disease (IBD). This study assessed the association between medication use and risk of developing IBD using the Prospective Urban Rural Epidemiology (PURE) cohort.This was a prospective cohort study of 133,137 individuals between the ages of 20-80 from 24 countries. Country-specific validated questionnaires documented baseline and follow-up medication use. Participants were followed prospectively at least every 3 years. The main outcome was development of IBD, including Crohn's disease (CD) and ulcerative colitis (UC). Short-term (baseline but not follow-up use) and long-term use (baseline and subsequent follow-up use) were evaluated. Results are presented as adjusted odds ratios (aOR) with 95% confidence intervals (CI).During a median follow-up of 11.0 years [interquartile range (IQR) 9.2-12.2], there were 571 incident IBD cases (143 CD and 428 UC). Incident IBD was significantly associated with baseline antibiotic [aOR: 2.81 (95% CI: 1.67-4.73), p=0.0001] and hormonal medication use [aOR: 4.43 (95% CI: 1.78-11.01), p=0.001]. Among females, previous or current oral contraceptive use was also associated with IBD development [aOR: 2.17 (95% CI: 1.70-2.77), p0.001]. NSAID users were also observed to have increased odds of IBD [aOR: 1.80 (95% CI: 1.23-2.64), p=0.002], which was driven by long-term use [aOR: 5.58 (95% CI: 2.26-13.80), p0.001]. All significant results were consistent in direction for CD and UC with low heterogeneity.Antibiotics, hormonal medications, oral contraceptives, and long-term NSAID use were associated with increased odds of incident IBD after adjustment for covariates.

Describe patient social needs in a large midwestern health care system. Health care systems are increasingly interested in addressing social needs in the clinical setting for improved health outcomes and lower costs. This retrospective cross-sectional analysis of health records data was a population health pilot project which tested a digital platform to screen and refer patients for social needs across three community hospitals serving Chicago and its South Suburbs. The analysis reports on social needs identified based on the referrals made. Electronic health record data were linked to the referral data to describe patient clinical and demographic characteristics. A total of 2909 patients had at least 1 social need identified. The mean age was 49 years ±21.7 and 65.7% were women. Only 33% of patients had 1 social need identified, indicating that if a social need is identified for patients, they most likely have social needs from other categories as well. Patients of color, specifically African American patients, were 14% more likely to have at least 3 social need categories identified (95% confidence interval of relative risk: 1.02-1.29). Financial stability was the most commonly reported social need (50.7%), followed by food and nutrition (43%). Transportation (22%) and housing (21%) were also commonly reported. This population health initiative reveals that many patients accessing health care have multiple social needs that can be identified at the point of care, and patterns of need-based referral vary by patient clinical and demographic characteristics.

Background There is a paucity of data on the prevalence of risk factors and their associations with incident cardiovascular disease in women compared with men, especially from low-income and middle-income countries. Methods In the Prospective Urban Rural Epidemiological (PURE) study, we enrolled participants from the general population from 21 high-income, middle-income, and low-income countries and followed them up for approximately 10 years. We recorded information on participants’ metabolic, behavioural, and psychosocial risk factors. For this analysis, we included participants aged 35–70 years at baseline without a history of cardiovascular disease, with at least one follow-up visit. The primary outcome was a composite of major cardiovascular events (cardiovascular disease deaths, myocardial infarction, stroke, and heart failure). We report the prevalence of each risk factor in women and men, their hazard ratios (HRs), and population-attributable fractions (PAFs) associated with major cardiovascular disease. The PURE study is registered with ClinicalTrials.gov, NCT03225586. Findings In this analysis, we included 155 724 participants enrolled and followed-up between Jan 5, 2005, and Sept 13, 2021, (90 934 [58·4%] women and 64 790 [41·6%] men), with a median follow-up of 10·1 years (IQR 8·5–12·0). At study entry, the mean age of women was 49·8 years (SD 9·7) compared with 50·8 years (9·8) in men. As of data cutoff (Sept 13, 2021), 4280 major cardiovascular disease events had occurred in women (age-standardised incidence rate of 5·0 events [95% CI 4·9–5·2] per 1000 person-years) and 4911 in men (8·2 [8·0–8·4] per 1000 person-years). Compared with men, women presented with a more favourable cardiovascular risk profile, especially at younger ages. The HRs for metabolic risk factors were similar in women and men, except for non-HDL cholesterol, for which high non-HDL cholesterol was associated with an HR for major cardiovascular disease of 1·11 (95% CI 1·01–1·21) in women and 1·28 (1·19–1·39) in men, with a consistent pattern for higher risk among men than among women with other lipid markers. Symptoms of depression had a HR of 1·09 (0·98–1·21) in women and 1·42 (1·25–1·60) in men. By contrast, consumption of a diet with a PURE score of 4 or lower (score ranges from 0 to 8), was more strongly associated with major cardiovascular disease in women (1·17 [1·08–1·26]) than in men (1·07 [0·99–1·15]). The total PAFs associated with behavioural and psychosocial risk factors were greater in men (15·7%) than in women (8·4%) predominantly due to the larger contribution of smoking to PAFs in men (ie, 1·3% [95% CI 0·5–2·1] in women vs 10·7% [8·8–12·6] in men). Interpretation Lipid markers and depression are more strongly associated with the risk of cardiovascular disease in men than in women, whereas diet is more strongly associated with the risk of cardiovascular disease in women than in men. The similar associations of other risk factors with cardiovascular disease in women and men emphasise the importance of a similar strategy for the prevention of cardiovascular disease in men and women.

A gap exists between clinical practice guidelines and real-world practice. We aim to investigate hospital admissions among patients presenting to emergency departments of 11 hospitals with venous thromboembolism (VTE). Eligible patients’ first emergency department VTE visit were retrospectively collected between 2013 and 2018 from electronic medical records (EMR). Patients were categorized at low risk of VTE complications if they were diagnosed with deep vein thrombosis (DVT) of the leg or if they were diagnosed with pulmonary embolism (PE) and had a PE score index

Digital, OBJECTIVE Previous prospective studies on the association of white rice intake with incident diabetes have shown contradictory results but were conducted in single countries and predominantly in Asia. We report on the association of white rice with risk of diabetes in the multinational Prospective Urban Rural Epidemiology (PURE) study. RESEARCH DESIGN AND METHODS Data on 132,373 individuals aged 35–70 years from 21 countries were analyzed. White rice consumption (cooked) was categorized as, Ciencias Médicas y de la Salud

Background The association of nuts with cardiovascular disease and deaths has been investigated mostly in Europe, the USA, and East Asia, with few data available from other regions of the world or from low- and middle-income countries. Objective To assess the association of nuts with mortality and cardiovascular disease (CVD). Methods The Prospective Urban Rural Epidemiology study is a large multinational prospective cohort study of adults aged 35–70 y from 16 low-, middle-, and high-income countries on 5 continents. Nut intake (tree nuts and ground nuts) was measured at the baseline visit, using country-specific validated FFQs. The primary outcome was a composite of mortality or major cardiovascular event [nonfatal myocardial infarction (MI), stroke, or heart failure]. Results We followed 124,329 participants (age = 50.7 y, SD = 10.2; 41.5% male) for a median of 9.5 y. We recorded 10,928 composite events [deaths (n = 8,662) or major cardiovascular events (n = 5,979)]. Higher nut intake (>120 g per wk compared with

Upper extremity deep vein thrombosis (UEDVT) accounts for ≤10% of DVT and can be associated with morbidity and mortality. Accurate diagnosis and treatment are necessary for safe and effective patient management. We systematically reviewed the accuracy of D-dimer and duplex ultrasonography (US) for the evaluation of suspected first-episode UEDVT. We searched the Cochrane Central Register, OVID MEDLINE, EMBASE, and PubMed for eligible studies, reference lists of relevant reviews, registered trials, and relevant conference proceedings. We included prospective cross-sectional and cohort studies that evaluated test accuracy. Two investigators independently screened and collected data. The risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies 2 and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. We pooled estimates of sensitivity and specificity. The review included 9 studies. The pooled estimates for D-dimer sensitivity and specificity were 0.96 (95% confidence interval [CI], 0.87-0.99) and 0.47 (95% CI, 0.43-0.52), respectively. The pooled estimates for duplex US sensitivity and specificity were 0.87 (95% CI, 0.73-0.94) and 0.85 (95% CI, 0.72-0.93), respectively. Certainty of evidence was moderate. In this review, we summarized the test accuracy (sensitivity and specificity) of D-dimer and duplex US for this indication. The sensitivity and specificity of the tests found in the present review should be considered in the context of whether they are used alone or in combination, which is dependent on the prevalence of disease in the population, the clinical setting in which the patient is being evaluated, cost, potential harms, and patient outcomes. This study was registered at PROSPERO as Systematic Review Registration Number CRD42018098488.

Deep vein thrombosis (DVT) of the lower extremities can be associated with significant morbidity and may progress to pulmonary embolism and postthrombotic syndrome. Early diagnosis and treatment are important to minimize the risk of these complications. We systematically reviewed the accuracy of diagnostic tests for first-episode and recurrent DVT of the lower extremities, including proximal compression ultrasonography (US), whole leg US, serial US, and high-sensitivity quantitative D-dimer assays. We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies, reference lists of relevant reviews, registered trials, and relevant conference proceedings. Two investigators screened and abstracted data. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. We pooled estimates of sensitivity and specificity. The review included 43 studies. For any suspected DVT, the pooled estimates for sensitivity and specificity of proximal compression US were 90.1% (95% confidence interval [CI], 86.5-92.8) and 98.5% (95% CI, 97.6-99.1), respectively. For whole-leg US, pooled estimates were 94.0% (95% CI, 91.3-95.9) and 97.3% (95% CI, 94.8-98.6); for serial US pooled estimates were 97.9% (95% CI, 96.0-98.9) and 99.8% (95% CI, 99.3-99.9). For D-dimer, pooled estimates were 96.1% (95% CI, 92.6-98.0) and 35.7% (95% CI, 29.5-42.4). Recurrent DVT studies were not pooled. Certainty of evidence varied from low to high. This systematic review of current diagnostic tests for DVT of the lower extremities provides accuracy estimates. The tests are evaluated when performed in a stand-alone fashion, and in a diagnostic pathway. The pretest probability of DVT often assessed by a clinical decision rule will influence how, together with sensitivity and specificity estimates, patients will be managed.

Summary Background To our knowledge, no previous study has prospectively documented the incidence of common diseases and related mortality in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) with standardised approaches. Such information is key to developing global and context-specific health strategies. In our analysis of the Prospective Urban Rural Epidemiology (PURE) study, we aimed to evaluate differences in the incidence of common diseases, related hospital admissions, and related mortality in a large contemporary cohort of adults from 21 HICs, MICs, and LICs across five continents by use of standardised approaches. Methods The PURE study is a prospective, population-based cohort study of individuals aged 35–70 years who have been enrolled from 21 countries across five continents. The key outcomes were the incidence of fatal and non-fatal cardiovascular diseases, cancers, injuries, respiratory diseases, and hospital admissions, and we calculated the age-standardised and sex-standardised incidence of these events per 1000 person-years. Findings This analysis assesses the incidence of events in 162 534 participants who were enrolled in the first two phases of the PURE core study, between Jan 6, 2005, and Dec 4, 2016, and who were assessed for a median of 9·5 years (IQR 8·5–10·9). During follow-up, 11 307 (7·0%) participants died, 9329 (5·7%) participants had cardiovascular disease, 5151 (3·2%) participants had a cancer, 4386 (2·7%) participants had injuries requiring hospital admission, 2911 (1·8%) participants had pneumonia, and 1830 (1·1%) participants had chronic obstructive pulmonary disease (COPD). Cardiovascular disease occurred more often in LICs (7·1 cases per 1000 person-years) and in MICs (6·8 cases per 1000 person-years) than in HICs (4·3 cases per 1000 person-years). However, incident cancers, injuries, COPD, and pneumonia were most common in HICs and least common in LICs. Overall mortality rates in LICs (13·3 deaths per 1000 person-years) were double those in MICs (6·9 deaths per 1000 person-years) and four times higher than in HICs (3·4 deaths per 1000 person-years). This pattern of the highest mortality in LICs and the lowest in HICs was observed for all causes of death except cancer, where mortality was similar across country income levels. Cardiovascular disease was the most common cause of deaths overall (40%) but accounted for only 23% of deaths in HICs (vs 41% in MICs and 43% in LICs), despite more cardiovascular disease risk factors (as judged by INTERHEART risk scores) in HICs and the fewest such risk factors in LICs. The ratio of deaths from cardiovascular disease to those from cancer was 0·4 in HICs, 1·3 in MICs, and 3·0 in LICs, and four upper-MICs (Argentina, Chile, Turkey, and Poland) showed ratios similar to the HICs. Rates of first hospital admission and cardiovascular disease medication use were lowest in LICs and highest in HICs. Interpretation Among adults aged 35–70 years, cardiovascular disease is the major cause of mortality globally. However, in HICs and some upper-MICs, deaths from cancer are now more common than those from cardiovascular disease, indicating a transition in the predominant causes of deaths in middle-age. As cardiovascular disease decreases in many countries, mortality from cancer will probably become the leading cause of death. The high mortality in poorer countries is not related to risk factors, but it might be related to poorer access to health care. Funding Full funding sources are listed at the end of the paper (see Acknowledgments).

Objectives: The objective of this study was to evaluate anticoagulant prescribing disparities in atrial fibrillation (AF) by exploring associations between social determinants of health (SDOH) collected from electronic health records (EHR) and oral anticoagulant (OAC) prescription. Methods: This retrospective study included adult patients newly diagnosed with AF who had ≥ 2 encounters from a large, integrated healthcare system between May 2016 and May 2021. Patient-level demographics, prescribing provider specialties, comorbidities, medications, and SDOH were extracted from EHRs. Area deprivation index (ADI) was linked to patient records as a measure of socioeconomic status. Patients were followed for 1 year from diagnosis. Multivariable logistic regression models were used to assess associations between SDOH, clinical factors, and OAC prescribing and class (warfarin or direct-acting OAC[DOAC]) of OAC prescribed. Results: Of 19,191 AF patients, 12,718 patients (66.3%) were prescribed an OAC within the first year of diagnosis. Mean age was 71.1 + 12.9 years, 43.9% (8,430 of 19,191) were females, and 91.2% (17,705 of 19,191) were white. Patients were less likely to be prescribed an OAC (relative risk [95% CI]) if they were widowed (0.98 [0.96-0.99] vs single) or had history of alcoholism (0.86 [0.79-0.95] vs no history). Most patients (53.3%) received prescriptions from a primary care provider. A linear relationship was found between worsening ADI and increased warfarin prescriptions compared with DOACs. Conclusion: Though guideline-concordant anticoagulation use remained suboptimal, clinical characteristics were strong predictors if an OAC was prescribed for AF stroke prevention. Worsening ADI was associated with an increased likelihood for patients to be prescribed warfarin instead of a DOAC.

ImportanceHypertension control remains suboptimal, particularly for Black and Hispanic or Latino patients. A need exists to improve hypertension management and design effective strategies to efficiently improve the quality of care in primary care, especially for these at-risk populations. Few studies have specifically explored perspectives on blood pressure management by primary care providers (PCPs) and patients.ObjectiveTo examine clinician and patient perspectives on barriers and facilitators to hypertension control within a racially and ethnically diverse health care system.Design, Setting, and ParticipantsThis qualitative study was conducted in a large urban US health care system from October 1, 2020, to March 31, 2021, among patients with a diagnosis of hypertension from a racially and ethnically diverse population, for a range of hypertension medication use hypertension control, as well as practicing PCPs. Analysis was conducted between June 2021 and February 2022 using immersion-crystallization methods.Main Outcomes and MeasuresPerspectives on managing blood pressure, including medication adherence and lifestyle, considerations for intensification, and experiences and gaps in using health information technology tools for hypertension, were explored using semistructured qualitative interviews. These cycles of review were continued until all data were examined and meaningful patterns were identified.ResultsInterviews were conducted with 30 participants: 15 patients (mean [SD] age, 58.6 [16.2] years; 10 women [67%] and 9 Black patients [60%]) and 15 clinicians (14 PCPs and 1 medical assistant; 8 women [53%]). Eleven patients (73%) had suboptimally controlled blood pressure. Participants reported a wide range of experiences with hypertension care, even within the same clinics and health care system. Five themes relevant to managing hypertension for racially and ethnically diverse patient populations in primary care were identified: (1) difficulty with self-management activities, especially lifestyle modifications; (2) hesitancy intensifying medications by both clinicians and patients; (3) varying the timing and follow-up after changes in medication; (4) variation in blood pressure self-monitoring recommendations and uptake; and (5) limited specific functionality of current health information technology tools.Conclusions and RelevanceIn this qualitative study of the views of PCPs and patients on hypertension control, the participants felt that more focus should be placed on lifestyle modifications than medications for hypertension, particularly for patients from racial and ethnic minority groups. Participants also expressed concerns about the existing functionality of health information technology tools to support increasingly asynchronous hypertension care. More intentional ways of supporting treatment intensification, self-care, and follow-up care are needed to improve hypertension management for racially and ethnically diverse populations in primary care.

Background Enhanced patient-provider engagement can improve patient health outcomes in chronic conditions, including major depressive disorder (MDD). Objective We evaluated the impact of a digitally enabled care mobile app, Pathway, designed to improve MDD patient-provider engagement. Patients used a mobile interface to assess treatment progress and share this information with primary care providers (PCPs). Methods In this 52-week, real-world effectiveness and feasibility study conducted in primary care clinics, 40 patients with MDD who were recently prescribed antidepressant monotherapy were randomized to use a mobile app with usual care (20/40, 50%) or usual care alone (20/40, 50%). Patients in the app arm engaged with the app daily for 18 weeks; a report was generated at 6-week intervals and shared with the PCPs to facilitate shared treatment decision-making discussions. The patients discontinued the app at week 18 and were followed through year 1. Coprimary outcome measures, assessed via research visits, included change from baseline in the 13-item Patient Activation Measure (PAM-13) and 7-item Patient-Provider Engagement Scale scores at week 18. Additional outcome measures included depression severity (9-item Patient Health Questionnaire [PHQ-9]) and cognitive symptoms (5-item Perceived Deficits Questionnaire–Depression). Results All 37 patients (app arm: n=18, 49%; usual care arm: n=19, 51%) who completed the 18-week follow-up period (n=31, 84% female, mean age 36, SD 11.3 years) had moderate to moderately severe depression. Improvements in PAM-13 and PHQ-9 scores were observed in both arms. Increases in PAM-13 scores from baseline to 18 weeks were numerically greater in the app arm than in the usual care arm (mean 10.5, SD 13.2 vs mean 8.8, SD 9.4; P=.65). At 52 weeks, differences in PAM-13 scores from baseline demonstrated significantly greater improvements in the app arm than in the usual care arm (mean 20.2, SD 17.7 vs mean 1.6, SD 14.2; P=.04). Compared with baseline, PHQ-9 scores decreased in both the app arm and the usual care arm at 18 weeks (mean 7.8, SD 7.2 vs mean 7.0, SD 6.5; P=.73) and 52 weeks (mean 9.5, SD 4.0 vs mean 4.7, SD 6.0; P=.07). Improvements in 7-item Patient-Provider Engagement Scale and WHO-5 scores were observed in both arms at 18 weeks and were sustained through 52 weeks in the app arm. Improvements in WHO-5 scores at 52 weeks were significantly greater in the app arm than in the usual care arm (41.5 vs 20.0; P=.02). Conclusions Patients with MDD will engage with a mobile app designed to track treatment and disease progression. PCPs will use the data generated as part of their assessment to inform clinical care. The study results suggest that an app-enabled clinical care pathway may enhance patient activation and benefit MDD management. Trial Registration ClinicalTrials.gov NCT03242213; https://clinicaltrials.gov/ct2/show/NCT03242213

Increasing evidence supports the safety and effectiveness of managing low-risk deep vein thrombosis (DVT) or pulmonary embolism (PE) in outpatient settings. We performed a systematic review to assess safety and effectiveness of managing patients with DVT or PE at home compared with the hospital. Medline, Embase, and Cochrane databases were searched up to July 2019 for relevant randomized clinical trials (RCTs), and prospective cohort studies. Two investigators independently screened titles and abstracts of identified citations and extracted data from relevant full-text papers. Risk ratios (RRs) were calculated, and certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Seven RCTs (1922 patients) were included in meta-analyses on managing patients with DVT. Pooled estimates indicated decreased risk of PE (RR = 0.64; 95% confidence interval [CI], 0.44-0.93) and recurrent DVT (RR = 0.61; 95% CI, 0.42-0.90) for home management, both with moderate certainty of the evidence. Reductions in mortality and major bleeding were not significant, both with low certainty of the evidence. Two RCTs (445 patients) were included in meta-analyses on home management of low-risk patients with PE. Pooled estimates indicated no significant difference in all-cause mortality, recurrent PE, and major bleeding, all with low certainty of the evidence. Results of pooled estimates from 3 prospective cohort studies (234 patients) on home management of PE showed similar results. Our findings indicate that low-risk DVT patients had similar or lower risk of patient-important outcomes with home treatment compared with hospital treatment. In patients with low-risk PE, there was important uncertainty about a difference between home and hospital treatment.

Background Socioeconomic status is associated with differences in risk factors for cardiovascular disease incidence and outcomes, including mortality. However, it is unclear whether the associations between cardiovascular disease and common measures of socioeconomic status—wealth and education—differ among high-income, middle-income, and low-income countries, and, if so, why these differences exist. We explored the association between education and household wealth and cardiovascular disease and mortality to assess which marker is the stronger predictor of outcomes, and examined whether any differences in cardiovascular disease by socioeconomic status parallel differences in risk factor levels or differences in management. Methods In this large-scale prospective cohort study, we recruited adults aged between 35 years and 70 years from 367 urban and 302 rural communities in 20 countries. We collected data on families and households in two questionnaires, and data on cardiovascular risk factors in a third questionnaire, which was supplemented with physical examination. We assessed socioeconomic status using education and a household wealth index. Education was categorised as no or primary school education only, secondary school education, or higher education, defined as completion of trade school, college, or university. Household wealth, calculated at the household level and with household data, was defined by an index on the basis of ownership of assets and housing characteristics. Primary outcomes were major cardiovascular disease (a composite of cardiovascular deaths, strokes, myocardial infarction, and heart failure), cardiovascular mortality, and all-cause mortality. Information on specific events was obtained from participants or their family. Findings Recruitment to the study began on Jan 12, 2001, with most participants enrolled between Jan 6, 2005, and Dec 4, 2014. 160 299 (87·9%) of 182 375 participants with baseline data had available follow-up event data and were eligible for inclusion. After exclusion of 6130 (3·8%) participants without complete baseline or follow-up data, 154 169 individuals remained for analysis, from five low-income, 11 middle-income, and four high-income countries. Participants were followed-up for a mean of 7·5 years. Major cardiovascular events were more common among those with low levels of education in all types of country studied, but much more so in low-income countries. After adjustment for wealth and other factors, the HR (low level of education vs high level of education) was 1·23 (95% CI 0·96–1·58) for high-income countries, 1·59 (1·42–1·78) in middle-income countries, and 2·23 (1·79–2·77) in low-income countries (pinteractionInterpretation Although people with a lower level of education in low-income and middle-income countries have higher incidence of and mortality from cardiovascular disease, they have better overall risk factor profiles. However, these individuals have markedly poorer health care. Policies to reduce health inequities globally must include strategies to overcome barriers to care, especially for those with lower levels of education. Funding Full funding sources are listed at the end of the paper (see Acknowledgments).

A growing body of literature now exists examining associations between social determinants of health (SDOH) and adverse outcomes in patients with atrial fibrillation; however, little is available on anticoagulant prescriptions and the impact of SDOH.Evaluate the impact of SDOH on anticoagulant prescriptions in patients with atrial fibrillation.Medline and Embase databases up to January 2021.Noninterventional studies were included if they reported associations between at least 1 of 14 SDOH domains and anticoagulant prescription in patients with atrial fibrillation. Two investigators independently screened and collected data.Two investigators independently screened and collected data.Meta-analyses using random-effect models evaluated associations between SDOH and receiving an anticoagulant prescription. We included 13 studies, 11 of which were included in meta-analyses that reported on the impact of 9 of the 14 SDOH included in the search. Pooled estimates indicate a 0.85 (95% confidence interval [CI]: 0.75, 0.97) lower odds of receiving anticoagulant prescriptions among Black compared to non-Black patients (reported in 6 studies); 0.42 (95% CI: 0.32, 0.55) lower odds of receiving anticoagulant prescriptions among patients with mental illness compared to those without mental illness (2 studies); and a 0.64 (95% CI: 0.42, 0.96) lower likelihood of receiving oral anticoagulant prescription among employed patients compared to unemployed patients (2 studies).SDOH lack consistent definitions and measures within the electronic health record.The literature reports on only half of the SDOH domains we searched for, indicating that many SDOH are not routinely assessed. Second, social needs impact the decision to prescribe anticoagulants, confirming the need to screen for and address social needs in the clinical setting to support clinicians in providing guideline concordant care to their patients.This systematic review and meta-analysis was registered with PROSPERO.

Digital, OBJECTIVE To evaluate the relation between intake of ultraprocessed food and risk of inflammatory bowel disease (IBD). DESIGN Prospective cohort study. SETTING 21 low, middle, and high income countries across seven geographical regions (Europe and North America, South America, Africa, Middle East, south Asia, South East Asia, and China). PARTICIPANTS 116087 adults aged 35-70 years with at least one cycle of follow-up and complete baseline food frequency questionnaire (FFQ) data (country specific validated FFQs were used to document baseline dietary intake). Participants were followed prospectively at least every three years. MAIN OUTCOME MEASURES The main outcome was development of IBD, including Crohn’s disease or ulcerative colitis. Associations between ultra-processed food intake and risk of IBD were assessed using Cox proportional hazard multivariable models. Results are presented as hazard ratios with 95% confidence intervals. RESULTS Participants were enrolled in the study between 2003 and 2016. During the median follow-up of 9.7 years (interquartile range 8.9-11.2 years), 467 participants developed incident IBD (90 with Crohn’s disease and 377 with ulcerative colitis). After adjustment for potential confounding factors, higher intake of ultra-processed food was associated with a higher risk of incident IBD (hazard ratio 1.82, 95% confidence interval 1.22 to 2.72 for ≥5 servings/day and 1.67, 1.18 to 2.37 for 1-4 servings/day compared with, Ciencias Médicas y de la Salud

Digital, Objective To examine the association between social isolation and mortality and incident diseases in middle-aged adults in urban and rural communities from high-income, middle-income and low-income countries. Design Population-based prospective observational study. Setting Urban and rural communities in 20 high income, middle income and low income. Participants 119894 community-dwelling middle-aged adults. Main outcome measures Associations of social isolation with mortality, cardiovascular death, non-cardiovascular death and incident diseases. Results Social isolation was more common in middleincome and high-income countries compared with lowincome countries, in urban areas than rural areas, in older individuals and among women, those with less education and the unemployed. It was more frequent among smokers and those with a poorer diet. Social isolation was associated with greater risk of mortality (HR of 1.26, 95% CI: 1.17 to 1.36), incident stroke (HR: 1.23, 95%CI: 1.07 to 1.40), cardiovascular disease (HR: 1.15, 95%CI: 1.05 to 1.25) and pneumonia (HR:1.22, 95%CI: 1.09 to 1.37), but not cancer. The associations between social isolation and mortality were observed in populations in high-income, middle-income and low-income countries (HR (95%CI): 1.69 (1.32 to 2.17), 1.27 (1.15 to 1.40) and 1.47 (1.25 to 1.73), respectively, interaction p=0.02). The HR associated with social isolation was greater in men than women and in younger than older individuals. Mediation analyses for the association between social isolation and mortality showed that unhealthy behaviours and comorbidities may account for about one-fifth of the association. Conclusion Social isolation is associated with increased risk of mortality in countries at different economic levels. The increasing share of older people in populations in many countries argues for targeted strategies to mitigate its adverse effects, Ciencias Médicas y de la Salud

Digital, Importance Cohort studies report inconsistent associations between fish consumption, a major source of long-chain ω-3 fatty acids, and risk of cardiovascular disease (CVD) and mortality. Whether the associations vary between those with and those without vascular disease is unknown. Objective To examine whether the associations of fish consumption with risk of CVD or of mortality differ between individuals with and individuals without vascular disease. Design, Setting, and Participants This pooled analysis of individual participant data involved 191 558 individuals from 4 cohort studies—147 645 individuals (139 827 without CVD and 7818 with CVD) from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study and 43 413 patients with vascular disease in 3 prospective studies from 40 countries. Adjusted hazard ratios (HRs) were calculated by multilevel Cox regression separately within each study and then pooled using random-effects meta-analysis. This analysis was conducted from January to June 2020. Exposures Fish consumption was recorded using validated food frequency questionnaires. In 1 of the cohorts with vascular disease, a separate qualitative food frequency questionnaire was used to assess intake of individual types of fish. Main Outcomes and Measures Mortality and major CVD events (including myocardial infarction, stroke, congestive heart failure, or sudden death). Results Overall, 191 558 participants with a mean (SD) age of 54.1 (8.0) years (91 666 [47.9%] male) were included in the present analysis. During 9.1 years of follow-up in PURE, compared with little or no fish intake (≤50 g/mo), an intake of 350 g/wk or more was not associated with risk of major CVD (HR, 0.95; 95% CI, 0.86-1.04) or total mortality (HR, 0.96; 0.88-1.05). By contrast, in the 3 cohorts of patients with vascular disease, the HR for risk of major CVD (HR, 0.84; 95% CI, 0.73-0.96) and total mortality (HR, 0.82; 95% CI, 0.74-0.91) was lowest with intakes of at least 175 g/wk (or approximately 2 servings/wk) compared with 50 g/mo or lower, with no further apparent decrease in HR with consumption of 350 g/wk or higher. Fish with higher amounts of ω-3 fatty acids were strongly associated with a lower risk of CVD (HR, 0.94; 95% CI, 0.92-0.97 per 5-g increment of intake), whereas other fish were neutral (collected in 1 cohort of patients with vascular disease). The association between fish intake and each outcome varied by CVD status, with a lower risk found among patients with vascular disease but not in general populations (for major CVD, I2 = 82.6 [P = .02]; for death, I2 = 90.8 [P = .001]). Conclusions and Relevance Findings of this pooled analysis of 4 cohort studies indicated that a minimal fish intake of 175 g (approximately 2 servings) weekly is associated with lower risk of major CVD and mortality among patients with prior CVD but not in general populations. The consumption of fish (especially oily fish) should be evaluated in randomized trials of clinical outcomes among people with vascular disease., Ciencias Médicas y de la Salud

Digital, Importance High amounts of sitting time are associated with increased risks of cardiovascular disease (CVD) and mortality in high-income countries, but it is unknown whether risks also increase in low- and middle-income countries. Objective To investigate the association of sitting time with mortality and major CVD in countries at different economic levels using data from the Prospective Urban Rural Epidemiology study. Design, Setting, and Participants This population-based cohort study included participants aged 35 to 70 years recruited from January 1, 2003, and followed up until August 31, 2021, in 21 high-income, middle-income, and low-income countries with a median follow-up of 11.1 years. Exposures Daily sitting time measured using the International Physical Activity Questionnaire. Main Outcomes and Measures The composite of all-cause mortality and major CVD (defined as cardiovascular death, myocardial infarction, stroke, or heart failure). Results Of 105 677 participants, 61 925 (58.6%) were women, and the mean (SD) age was 50.4 (9.6) years. During a median follow-up of 11.1 (IQR, 8.6-12.2) years, 6233 deaths and 5696 major cardiovascular events (2349 myocardial infarctions, 2966 strokes, 671 heart failure, and 1792 cardiovascular deaths) were documented. Compared with the reference group (, Ciencias Médicas y de la Salud

Digital, BACKGROUND Most data regarding the association between the glycemic index and cardiovascular disease come from high-income Western populations, with little information from non-Western countries with low or middle incomes. To fill this gap, data are needed from a large, geographically diverse population. METHODS This analysis includes 137,851 participants between the ages of 35 and 70 years living on five continents, with a median follow-up of 9.5 years. We used countryspecific food-frequency questionnaires to determine dietary intake and estimated the glycemic index and glycemic load on the basis of the consumption of seven categories of carbohydrate foods. We calculated hazard ratios using multivariable Cox frailty models. The primary outcome was a composite of a major cardiovascular event (cardiovascular death, nonfatal myocardial infarction, stroke, and heart failure) or death from any cause. RESULTS In the study population, 8780 deaths and 8252 major cardiovascular events occurred during the follow-up period. After performing extensive adjustments comparing the lowest and highest glycemic-index quintiles, we found that a diet with a high glycemic index was associated with an increased risk of a major cardiovascular event or death, both among participants with preexisting cardiovascular disease (hazard ratio, 1.51; 95% confidence interval [CI], 1.25 to 1.82) and among those without such disease (hazard ratio, 1.21; 95% CI, 1.11 to 1.34). Among the components of the primary outcome, a high glycemic index was also associated with an increased risk of death from cardiovascular causes. The results with respect to glycemic load were similar to the findings regarding the glycemic index among the participants with cardiovascular disease at baseline, but the association was not significant among those without preexisting cardiovascular disease. CONCLUSIONS In this study, a diet with a high glycemic index was associated with an increased risk of cardiovascular disease and death. (Funded by the Population Health Research Institute and others.), Ciencias Médicas y de la Salud

Background While it is known that sex and race/ethnic disparities persist for atherosclerotic cardiovascular disease (ASCVD), disparities in risk factor control have not been well-described in primary care where ASCVD can be prevented. Methods Adult patients with a hypertension diagnosis without ASCVD were included in this analysis of electronic health records from a large US healthcare system from 2018. Patients were categorized based on risk factor control defined as blood pressure (BP), Graphical Abstract Graphical Abstract

Pulmonary embolism (PE) is a common, potentially life-threatening yet treatable condition. Prompt diagnosis and expeditious therapeutic intervention is of paramount importance for optimal patient management. Our objective was to systematically review the accuracy of D-dimer assay, compression ultrasonography (CUS), computed tomography pulmonary angiography (CTPA), and ventilation-perfusion (V/Q) scanning for the diagnosis of suspected first and recurrent PE. We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies, reference lists of relevant reviews, registered trials, and relevant conference proceedings. 2 investigators screened and abstracted data. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. We pooled estimates of sensitivity and specificity. The review included 61 studies. The pooled estimates for D-dimer sensitivity and specificity were 0.97 (95% confidence interval [CI], 0.96-0.98) and 0.41 (95% CI, 0.36-0.46) respectively, whereas CTPA sensitivity and specificity were 0.94 (95% CI, 0.89-0.97) and 0.98 (95% CI, 0.97-0.99), respectively, and CUS sensitivity and specificity were 0.49 (95% CI, 0.31-0.66) and 0.96 (95% CI, 0.95-0.98), respectively. Three variations of pooled estimates for sensitivity and specificity of V/Q scan were carried out, based on interpretation of test results. D-dimer had the highest sensitivity when compared with imaging. CTPA and V/Q scans (high probability scan as a positive and low/non-diagnostic/normal scan as negative) both had the highest specificity. This systematic review was registered on PROSPERO as CRD42018084669.

Dietary guidelines recommend limiting red meat intake because it is a major source of medium- and long-chain SFAs and is presumed to increase the risk of cardiovascular disease (CVD). Evidence of an association between unprocessed red meat intake and CVD is inconsistent.The study aimed to assess the association of unprocessed red meat, poultry, and processed meat intake with mortality and major CVD.The Prospective Urban Rural Epidemiology (PURE) Study is a cohort of 134,297 individuals enrolled from 21 low-, middle-, and high-income countries. Food intake was recorded using country-specific validated FFQs. The primary outcomes were total mortality and major CVD. HRs were estimated using multivariable Cox frailty models with random intercepts.In the PURE study, during 9.5 y of follow-up, we recorded 7789 deaths and 6976 CVD events. Higher unprocessed red meat intake (≥250 g/wk vs.50 g/wk) was not significantly associated with total mortality (HR: 0.93; 95% CI: 0.85, 1.02; P-trend = 0.14) or major CVD (HR: 1.01; 95% CI: 0.92, 1.11; P-trend = 0.72). Similarly, no association was observed between poultry intake and health outcomes. Higher intake of processed meat (≥150 g/wk vs. 0 g/wk) was associated with higher risk of total mortality (HR: 1.51; 95% CI: 1.08, 2.10; P-trend = 0.009) and major CVD (HR: 1.46; 95% CI: 1.08, 1.98; P-trend = 0.004).In a large multinational prospective study, we did not find significant associations between unprocessed red meat and poultry intake and mortality or major CVD. Conversely, a higher intake of processed meat was associated with a higher risk of mortality and major CVD.

Summary Background Most studies of long-term exposure to outdoor fine particulate matter (PM2·5) and cardiovascular disease are from high-income countries with relatively low PM2·5 concentrations. It is unclear whether risks are similar in low-income and middle-income countries (LMICs) and how outdoor PM2·5 contributes to the global burden of cardiovascular disease. In our analysis of the Prospective Urban and Rural Epidemiology (PURE) study, we aimed to investigate the association between long-term exposure to PM2·5 concentrations and cardiovascular disease in a large cohort of adults from 21 high-income, middle-income, and low-income countries. Methods In this multinational, prospective cohort study, we studied 157 436 adults aged 35–70 years who were enrolled in the PURE study in countries with ambient PM2·5 estimates, for whom follow-up data were available. Cox proportional hazard frailty models were used to estimate the associations between long-term mean community outdoor PM2·5 concentrations and cardiovascular disease events (fatal and non-fatal), cardiovascular disease mortality, and other non-accidental mortality. Findings Between Jan 1, 2003, and July 14, 2018, 157 436 adults from 747 communities in 21 high-income, middle-income, and low-income countries were enrolled and followed up, of whom 140 020 participants resided in LMICs. During a median follow-up period of 9·3 years (IQR 7·8–10·8; corresponding to 1·4 million person-years), we documented 9996 non-accidental deaths, of which 3219 were attributed to cardiovascular disease. 9152 (5·8%) of 157 436 participants had cardiovascular disease events (fatal and non-fatal incident cardiovascular disease), including 4083 myocardial infarctions and 4139 strokes. Mean 3-year PM2·5 at cohort baseline was 47·5 μg/m3 (range 6–140). In models adjusted for individual, household, and geographical factors, a 10 μg/m3 increase in PM2·5 was associated with increased risk for cardiovascular disease events (hazard ratio 1·05 [95% CI 1·03–1·07]), myocardial infarction (1·03 [1·00–1·05]), stroke (1·07 [1·04–1·10]), and cardiovascular disease mortality (1·03 [1·00–1·05]). Results were similar for LMICs and communities with high PM2·5 concentrations (>35 μg/m3). The population attributable fraction for PM2·5 in the PURE cohort was 13·9% (95% CI 8·8–18·6) for cardiovascular disease events, 8·4% (0·0–15·4) for myocardial infarction, 19·6% (13·0–25·8) for stroke, and 8·3% (0·0–15·2) for cardiovascular disease mortality. We identified no consistent associations between PM2·5 and risk for non-cardiovascular disease deaths. Interpretation Long-term outdoor PM2·5 concentrations were associated with increased risks of cardiovascular disease in adults aged 35–70 years. Air pollution is an important global risk factor for cardiovascular disease and a need exists to reduce air pollution concentrations, especially in LMICs, where air pollution levels are highest. Funding Full funding sources are listed at the end of the paper (see Acknowledgments).

Prompt evaluation and therapeutic intervention of suspected pulmonary embolism (PE) are of paramount importance for improvement in outcomes. We systematically reviewed outcomes in patients with suspected PE, including mortality, incidence of recurrent PE, major bleeding, intracranial hemorrhage, and postthrombotic sequelae. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase for eligible studies, reference lists of relevant reviews, registered trials, and relevant conference proceedings. We included 22 studies with 15 865 patients. Among patients who were diagnosed with PE and discharged with anticoagulation, 3-month follow-up revealed that all-cause mortality was 5.69% (91/1599; 95% confidence interval [CI], 4.56-6.83), mortality from PE was 1.19% (19/1597; 95% CI, 0.66-1.72), recurrent venous thromboembolism (VTE) occurred in 1.38% (22/1597; 95% CI: 0.81-1.95), and major bleeding occurred in 0.90% (2/221%; 95% CI, 0-2.15). In patients with a low pretest probability (PTP) and negative D-dimer, 3-month follow-up revealed mortality from PE was 0% (0/808) and incidence of VTE was 0.37% (4/1094; 95% CI: 0.007-0.72). In patients with intermediate PTP and negative D-dimer, 3-month follow-up revealed that mortality from PE was 0% (0/2747) and incidence of VTE was 0.46% (14/3015; 95% CI: 0.22-0.71). In patients with high PTP and negative computed tomography (CT) scan, 3-month follow-up revealed mortality from PE was 0% (0/651) and incidence of VTE was 0.84% (11/1302; 95% CI: 0.35-1.34). We further summarize outcomes evaluated by various diagnostic tests and diagnostic pathways (ie, D-dimer followed by CT scan).

ObjectivesWe aimed to examine the relationship between access to medicine for cardiovascular disease (CVD) and major adverse cardiovascular events (MACEs) among people at high risk of CVD in high-income countries (HICs), upper and lower middle-income countries (UMICs, LMICs) and low-income countries (LICs) participating in the Prospective Urban Rural Epidemiology (PURE) study.MethodsWe defined high CVD risk as the presence of any of the following: hypertension, coronary artery disease, stroke, smoker, diabetes or age >55 years. Availability and affordability of blood pressure lowering drugs, antiplatelets and statins were obtained from pharmacies. Participants were categorised: group 1—all three drug types were available and affordable, group 2—all three drugs were available but not affordable and group 3—all three drugs were not available. We used multivariable Cox proportional hazard models with nested clustering at country and community levels, adjusting for comorbidities, sociodemographic and economic factors.ResultsOf 163 466 participants, there were 93 200 with high CVD risk from 21 countries (mean age 54.7, 49% female). Of these, 44.9% were from group 1, 29.4% from group 2 and 25.7% from group 3. Compared with participants from group 1, the risk of MACEs was higher among participants in group 2 (HR 1.19, 95% CI 1.07 to 1.31), and among participants from group 3 (HR 1.25, 95% CI 1.08 to 1.50).ConclusionLower availability and affordability of essential CVD medicines were associated with higher risk of MACEs and mortality. Improving access to CVD medicines should be a key part of the strategy to lower CVD globally.

Digital, Objective Our aims were to assess the association of dairy intake with prevalence of metabolic syndrome (MetS) (cross-sectionally) and with incident hypertension and incident diabetes (prospectively) in a large multinational cohort study. Methods The Prospective Urban Rural Epidemiology (PURE) study is a prospective epidemiological study of individuals aged 35 and 70 years from 21 countries on five continents, with a median follow-up of 9.1 years. In the cross-sectional analyses, we assessed the association of dairy intake with prevalent MetS and its components among individuals with information on the five MetS components (n=112 922). For the prospective analyses, we examined the association of dairy with incident hypertension (in 57 547 individuals free of hypertension) and diabetes (in 131 481 individuals free of diabetes). Results In cross-sectional analysis, higher intake of total dairy (at least two servings/day compared with zero intake; OR 0.76, 95% CI 0.71 to 0.80, p-trend, Ciencias Médicas y de la Salud

Aims To investigate the association of estimated total daily sleep duration and daytime nap duration with deaths and major cardiovascular events. Methods and results We estimated the durations of total daily sleep and daytime naps based on the amount of time in bed and self-reported napping time and examined the associations between them and the composite outcome of deaths and major cardiovascular events in 116 632 participants from seven regions. After a median follow-up of 7.8 years, we recorded 4381 deaths and 4365 major cardiovascular events. It showed both shorter (≤6 h/day) and longer (>8 h/day) estimated total sleep durations were associated with an increased risk of the composite outcome when adjusted for age and sex. After adjustment for demographic characteristics, lifestyle behaviours and health status, a J-shaped association was observed. Compared with sleeping 6–8 h/day, those who slept ≤6 h/day had a non-significant trend for increased risk of the composite outcome [hazard ratio (HR), 1.09; 95% confidence interval, 0.99–1.20]. As estimated sleep duration increased, we also noticed a significant trend for a greater risk of the composite outcome [HR of 1.05 (0.99–1.12), 1.17 (1.09–1.25), and 1.41 (1.30–1.53) for 8–9 h/day, 9–10 h/day, and >10 h/day, P trend < 0.0001, respectively]. The results were similar for each of all-cause mortality and major cardiovascular events. Daytime nap duration was associated with an increased risk of the composite events in those with over 6 h of nocturnal sleep duration, but not in shorter nocturnal sleepers (≤6 h). Conclusion Estimated total sleep duration of 6–8 h per day is associated with the lowest risk of deaths and major cardiovascular events. Daytime napping is associated with increased risks of major cardiovascular events and deaths in those with >6 h of nighttime sleep but not in those sleeping ≤6 h/night.

Summary Background Data are scarce on the availability and affordability of essential medicines for diabetes. Our aim was to examine the availability and affordability of metformin, sulfonylureas, and insulin across multiple regions of the world and explore the effect of these on medicine use. Methods In the Prospective Urban Rural Epidemiology (PURE) study, participants aged 35–70 years (n=156 625) were recruited from 110 803 households, in 604 communities and 22 countries; availability (presence of any dose of medication in the pharmacy on the day of audit) and medicine cost data were collected from pharmacies with the Environmental Profile of a Community's Health audit tool. Our primary analysis was to describe the availability and affordability of metformin and insulin and also commonly used and prescribed combinations of two medicines for diabetes management (two oral drugs, metformin plus a sulphonylurea [either glibenclamide (also known as glyburide) or gliclazide] and one oral drug plus insulin [metformin plus insulin]). Medicines were defined as affordable if the cost of medicines was less than 20% of capacity-to-pay (the household income minus food expenditure). Our analyses included data collected in pharmacies and data from representative samples of households. Data on availability were ascertained during the pharmacy audit, as were data on cost of medications. These cost data were used to estimate the cost of a month's supply of essential medicines for diabetes. We estimated affordability of medicines using income data from household surveys. Findings Metformin was available in 113 (100%) of 113 pharmacies from high-income countries, 112 (88·2%) of 127 pharmacies in upper-middle-income countries, 179 (86·1%) of 208 pharmacies in lower-middle-income countries, 44 (64·7%) of 68 pharmacies in low-income countries (excluding India), and 88 (100%) of 88 pharmacies in India. Insulin was available in 106 (93·8%) pharmacies in high-income countries, 51 (40·2%) pharmacies in upper-middle-income countries, 61 (29·3%) pharmacies in lower-middle-income countries, seven (10·3%) pharmacies in lower-income countries, and 67 (76·1%) of 88 pharmacies in India. We estimated 0·7% of households in high-income countries and 26·9% of households in low-income countries could not afford metformin and 2·8% of households in high-income countries and 63·0% of households in low-income countries could not afford insulin. Among the 13 569 (8·6% of PURE participants) that reported a diagnosis of diabetes, 1222 (74·0%) participants reported diabetes medicine use in high-income countries compared with 143 (29·6%) participants in low-income countries. In multilevel models, availability and affordability were significantly associated with use of diabetes medicines. Interpretation Availability and affordability of essential diabetes medicines are poor in low-income and middle-income countries. Awareness of these global differences might importantly drive change in access for patients with diabetes. Funding Full funding sources listed at the end of the paper (see Acknowledgments).

WHO recommends that populations consume less than 2 g/day sodium as a preventive measure against cardiovascular disease, but this target has not been achieved in any country. This recommendation is primarily based on individual-level data from short-term trials of blood pressure (BP) without data relating low sodium intake to reduced cardiovascular events from randomised trials or observational studies. We investigated the associations between community-level mean sodium and potassium intake, cardiovascular disease, and mortality.The Prospective Urban Rural Epidemiology study is ongoing in 21 countries. Here we report an analysis done in 18 countries with data on clinical outcomes. Eligible participants were adults aged 35-70 years without cardiovascular disease, sampled from the general population. We used morning fasting urine to estimate 24 h sodium and potassium excretion as a surrogate for intake. We assessed community-level associations between sodium and potassium intake and BP in 369 communities (all50 participants) and cardiovascular disease and mortality in 255 communities (all100 participants), and used individual-level data to adjust for known confounders.95 767 participants in 369 communities were assessed for BP and 82 544 in 255 communities for cardiovascular outcomes with follow-up for a median of 8·1 years. 82 (80%) of 103 communities in China had a mean sodium intake greater than 5 g/day, whereas in other countries 224 (84%) of 266 communities had a mean intake of 3-5 g/day. Overall, mean systolic BP increased by 2·86 mm Hg per 1 g increase in mean sodium intake, but positive associations were only seen among the communities in the highest tertile of sodium intake (p0·0001 for heterogeneity). The association between mean sodium intake and major cardiovascular events showed significant deviations from linearity (p=0·043) due to a significant inverse association in the lowest tertile of sodium intake (lowest tertile4·43 g/day, mean intake 4·04 g/day, range 3·42-4·43; change -1·00 events per 1000 years, 95% CI -2·00 to -0·01, p=0·0497), no association in the middle tertile (middle tertile 4·43-5·08 g/day, mean intake 4·70 g/day, 4·44-5.05; change 0·24 events per 1000 years, -2·12 to 2·61, p=0·8391), and a positive but non-significant association in the highest tertile (highest tertile5·08 g/day, mean intake 5·75 g/day,5·08-7·49; change 0·37 events per 1000 years, -0·03 to 0·78, p=0·0712). A strong association was seen with stroke in China (mean sodium intake 5·58 g/day, 0·42 events per 1000 years, 95% CI 0·16 to 0·67, p=0·0020) compared with in other countries (4·49 g/day, -0·26 events, -0·46 to -0·06, p=0·0124; p0·0001 for heterogeneity). All major cardiovascular outcomes decreased with increasing potassium intake in all countries.Sodium intake was associated with cardiovascular disease and strokes only in communities where mean intake was greater than 5 g/day. A strategy of sodium reduction in these communities and countries but not in others might be appropriate.Population Health Research Institute, Canadian Institutes of Health Research, Canadian Institutes of Health Canada Strategy for Patient-Oriented Research, Ontario Ministry of Health and Long-Term Care, Heart and Stroke Foundation of Ontario, and European Research Council.

Introduction Portable spirometers are commonly used in longitudinal epidemiological studies to measure and track the forced expiratory volume in first second (FEV1) and forced vital capacity (FVC). During the course of the study, it may be necessary to replace spirometers with a different model. This raise questions regarding the comparability of measurements from different devices. We examined the correlation, mean differences and agreement between two different spirometers, across diverse populations and different participant characteristics. Methods From June 2015 to Jan 2018, a total of 4,603 adults were enrolled from 628 communities in 18 countries and 7 regions of the world. Each participant performed concurrent measurements from the MicroGP and EasyOne spirometer. Measurements were compared by the intra-class correlation coefficient (ICC) and Bland-Altman method. Results Approximately 65% of the participants achieved clinically acceptable quality measurements. Overall correlations between paired FEV1 (ICC 0.88 [95% CI 0.87, 0.88]) and FVC (ICC 0.84 [0.83, 0.85]) were high. Mean differences between paired FEV1 (-0.038 L [-0.053, -0.023]) and FVC (0.033 L [0.012, 0.054]) were small. The 95% limits of agreement were wide but unbiased (FEV1 984, -1060; FVC 1460, -1394). Similar findings were observed across regions. The source of variation between spirometers was mainly at the participant level. Older age, higher body mass index, tobacco smoking and known COPD/asthma did not adversely impact on the inter-device variability. Furthermore, there were small and acceptable mean differences between paired FEV1 and FVC z-scores using the Global Lung Initiative normative values, suggesting minimal impact on lung function interpretation. Conclusions In this multicenter, diverse community-based cohort study, measurements from two portable spirometers provided good correlation, small and unbiased differences between measurements. These data support their interchangeable use across diverse populations to provide accurate trends in serial lung function measurements in epidemiological studies.

Background: For patients with VTE, current American Society of Hematology (ASH) guideline panel suggests using direct oral anticoagulants (DOACs) over vitamin K antagonists (VKAs) where VKAs are required to be bridged with a parenteral anticoagulant (PAC). For patients with VTE and cancer, current guidelines recommend DOACs over low molecular weight heparin (LMWH) and LMWH over unfractionated heparin (heparin) for the initial treatment of VTE. Limited evidence is available about the patterns of anticoagulant treatment for VTE in routine clinical practice of large healthcare delivery networks in the United States (US) and whether the VTE treatments are aligned with current guidelines. This study aimed to assess real-world anticoagulant treatment patterns among VTE patients using harmonized electronic health record (EHR) data from four Integrated Delivery Networks (IDNs) in the US. Methods: This was a retrospective, longitudinal, multicenter, cohort study using harmonized EHR data from both inpatient and outpatient settings. The study population included adult patients prescribed DOACs, warfarin, and/or PAC therapy as inpatient or outpatient treatment within ≤30 days of VTE diagnosis, between June 2015 through May 2018. Data from the four IDNs was pooled to describe demographic characteristics and treatment patterns among VTE patients overall and by subgroups. Results: A total of 10,527 patients who were treated with OACs after VTE diagnosis were included for analysis. The mean (SD) age was 61.9 (5.98) years, with 46.1% aged 65 or older. More than half (53.2%) were female, and White patients comprised the majority (74.4%), followed by African American patients (22.8%). Obese and morbidly obese patients comprised 39.1% and 16.1% of patients, respectively. Among all VTE patients, warfarin-only (n=3545; 33.7%) was the most commonly used OAC treatment, followed by warfarin + PAC (n=3128; 29.7%), rivaroxaban-only (n=1357; 12.9%), rivaroxaban + PAC (n=853; 8.1%), apixaban + PAC (n=839; 8.0%), apixaban-only (n=762; 7.2%), and Other OAC (n=357; 3.4%) (Table 1). When stratifying VTE patients by age, gender, race and BMI, some variations in OAC treatment were observed. Among both older (≥65 years) and younger ( Patterns of anticoagulant treatments including OACs and/or parental anticoagulants among VTE patients with cancer were further analyzed (Figure 1). Among VTE patients with cancer (n=3657), heparin had the highest use (26.7%), then enoxaparin (22.7%); approximately the same proportion of cancer patients received warfarin-only (16.0%) and warfarin + PAC (16.9%). Of DOACs, rivaroxaban-only was the most commonly used treatment (4.9%), then apixaban + PAC (3.5%), and lastly, rivaroxaban + PAC (3.4%) among cancer patients. Conclusion: Current VTE treatment guidelines recommend warfarin to be bridged with PAC, however, warfarin-only therapy remained the most used treatment option followed by warfarin + PAC. While rivaroxaban and apixaban are not required to be bridged with PAC, such practices were observed for a large proportion of apixaban- and rivaroxaban-treated VTE patients. VTE treatment among patients with cancer was not completely aligned with current guidelines, as heparin was more commonly used than LMWH (enoxaparin). Our findings suggest greater efforts are needed to improve anticoagulant treatment practices among VTE patients. Figure 1 Figure 1. Disclosures Dhamane: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Rosenblatt: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Jiang: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Guo: Bristol Myers Squibb: Ended employment in the past 24 months. Dorsch: Agency for Health Research and Quality: Research Funding; National Institutes of Health/National Institute of Aging: Research Funding; American Health Association Health IT Research Network: Research Funding; Janssen Pharmaceuticals: Honoraria; Bristol Myers Squibb/Pfizer: Research Funding; Amgen: Research Funding. Luo: Pfizer Inc: Current Employment, Current equity holder in publicly-traded company.

Background: SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated a 27% reduction in all-cause mortality with a systolic blood pressure (SBP) goal of Methods: SPRINT eligibility criteria were applied to the 1999 to 2006 National Health and Nutrition Examination Survey and linked with the National Death Index through December 2011. SPRINT eligibility included age ≥50 years, SBP of 130 to 180 mm Hg (depending on the number of antihypertensive medications being taken), and high cardiovascular disease risk. Exclusion criteria were diabetes mellitus, history of stroke, >1 g proteinuria, heart failure, estimated glomerular filtration rate −1 ·1.73 m −2 , or dialysis. Annual mortality rates were calculated by dividing the Kaplan-Meier 5-year mortality by 5. Hazard ratios for all-cause mortality and heart failure and absolute risks for serious adverse events in SPRINT were used to estimate the number of potential deaths and heart failure cases prevented and serious adverse events incurred with intensive SBP treatment. Results: The mean age was 68.6 years, and 83.2% and 7.4% were non-Hispanic white and non-Hispanic black, respectively. The annual mortality rate was 2.20% (95% confidence interval [CI], 1.91–2.48), and intensive SBP treatment was projected to prevent ≈107 500 deaths per year (95% CI, 93 300–121 200) and give rise to 56 100 (95% CI, 50 800–61 400) episodes of hypotension, 34 400 (95% CI, 31 200–37 600) episodes of syncope, 43 400 (95% CI, 39 400–47 500) serious electrolyte disorders, and 88 700 (95% CI, 80 400–97 000) cases of acute kidney injury per year. The analysis-of-extremes approach indicated that the range of estimated lower- and upper-bound number of deaths prevented per year with intensive SBP control was 34 600 to 179 600. Intensive SBP control was projected to prevent 46 100 (95% CI, 41 800–50 400) cases of heart failure annually. Conclusions: If fully implemented in eligible US adults, intensive SBP treatment could prevent ≈107 500 deaths per year. A consequence of this treatment strategy, however, could be an increase in serious adverse events.

Digital, Background Non-communicable diseases (NCDs) are the leading cause of death globally. In 2014, the United Nations committed to reducing premature mortality from NCDs, including by reducing the burden of healthcare costs. Since 2014, the Prospective Urban and Rural Epidemiology (PURE) Study has been collecting health expenditure data from households with NCDs in 18 countries. Methods Using data from the PURE Study, we estimated risk of catastrophic health spending and impoverishment among households with at least one person with NCDs (cardiovascular disease, diabetes, kidney disease, cancer and respiratory diseases; n=17 435), with hypertension only (a leading risk factor for NCDs; n=11 831) or with neither (n=22 654) by country income group: high-income countries (Canada and Sweden), upper middle income countries (UMICs: Brazil, Chile, Malaysia, Poland, South Africa and Turkey), lower middle income countries (LMICs: the Philippines, Colombia, India, Iran and the Occupied Palestinian Territory) and low-income countries (LICs: Bangladesh, Pakistan, Zimbabwe and Tanzania) and China. Results The prevalence of catastrophic spending and impoverishment is highest among households with NCDs in LMICs and China. After adjusting for covariates that might drive health expenditure, the absolute risk of catastrophic spending is higher in households with NCDs compared with no NCDs in LMICs (risk difference=1.71%; 95% CI 0.75 to 2.67), UMICs (0.82%; 95% CI 0.37 to 1.27) and China (7.52%; 95% CI 5.88 to 9.16). A similar pattern is observed in UMICs and China for impoverishment. A high proportion of those with NCDs in LICs, especially women (38.7% compared with 12.6% in men), reported not taking medication due to costs. Conclusions Our findings show that financial protection from healthcare costs for people with NCDs is inadequate, particularly in LMICs and China. While the burden of NCD care may appear greatest in LMICs and China, the burden in LICs may be masked by care foregone due to costs. The high proportion of women reporting foregone care due to cost may in part explain gender inequality in treatment of NCDs., Ciencias Médicas y de la Salud

After deep vein thrombosis (DVT) is diagnosed, prompt evaluation and therapeutic intervention are of paramount importance for improvement in patient-important outcomes. We systematically reviewed patient-important outcomes in patients with suspected DVT, including mortality, incidence of pulmonary embolism (PE) and DVT, major bleeding, intracranial hemorrhage, and postthrombotic sequelae. We searched the Cochrane Central Register of Controlled Trials, Ovid Medline, Embase for eligible studies, references lists of relevant reviews, registered trials, and relevant conference proceedings. Two investigators screened and abstracted data. Nine studies with 5126 patients were included for lower extremity DVT. Three studies with 500 patients were included for upper extremity DVT. Among patients with lower extremity DVT, 0.85% (95% confidence interval [CI], 0% to 2.10%) and 0% developed recurrent DVT and PE, respectively, at 3 months. Among patients with upper extremity DVT, 0.49% (95% CI, 0% to 1.16%) and 1.98% (95% CI, 0.62% to 3.33%) developed recurrent DVT and PE, respectively, at 3 months. No major bleeding events were reported for those anticoagulated, which is lower than in other systematic reviews. For both upper and lower extremity DVT, low pretest probability patients with a negative D-dimer had a comparable incidence of VTE at 3 months (∼1%) as patients with a negative ultrasound (US). At higher pretest probabilities, negative US testing with or without serial US appears to be the safer option. In this review, we summarized the outcomes of patients evaluated by various diagnostic pathways. In most instances, there was significant limitation due to small population size or lack of direct evidence of effects of using a specific pathway. This systematic review was registered at PROSPERO as CRD42018100502.

Summary Background Global estimates of the effect of common modifiable risk factors on cardiovascular disease and mortality are largely based on data from separate studies, using different methodologies. The Prospective Urban Rural Epidemiology (PURE) study overcomes these limitations by using similar methods to prospectively measure the effect of modifiable risk factors on cardiovascular disease and mortality across 21 countries (spanning five continents) grouped by different economic levels. Methods In this multinational, prospective cohort study, we examined associations for 14 potentially modifiable risk factors with mortality and cardiovascular disease in 155 722 participants without a prior history of cardiovascular disease from 21 high-income, middle-income, or low-income countries (HICs, MICs, or LICs). The primary outcomes for this paper were composites of cardiovascular disease events (defined as cardiovascular death, myocardial infarction, stroke, and heart failure) and mortality. We describe the prevalence, hazard ratios (HRs), and population-attributable fractions (PAFs) for cardiovascular disease and mortality associated with a cluster of behavioural factors (ie, tobacco use, alcohol, diet, physical activity, and sodium intake), metabolic factors (ie, lipids, blood pressure, diabetes, obesity), socioeconomic and psychosocial factors (ie, education, symptoms of depression), grip strength, and household and ambient pollution. Associations between risk factors and the outcomes were established using multivariable Cox frailty models and using PAFs for the entire cohort, and also by countries grouped by income level. Associations are presented as HRs and PAFs with 95% CIs. Findings Between Jan 6, 2005, and Dec 4, 2016, 155 722 participants were enrolled and followed up for measurement of risk factors. 17 249 (11·1%) participants were from HICs, 102 680 (65·9%) were from MICs, and 35 793 (23·0%) from LICs. Approximately 70% of cardiovascular disease cases and deaths in the overall study population were attributed to modifiable risk factors. Metabolic factors were the predominant risk factors for cardiovascular disease (41·2% of the PAF), with hypertension being the largest (22·3% of the PAF). As a cluster, behavioural risk factors contributed most to deaths (26·3% of the PAF), although the single largest risk factor was a low education level (12·5% of the PAF). Ambient air pollution was associated with 13·9% of the PAF for cardiovascular disease, although different statistical methods were used for this analysis. In MICs and LICs, household air pollution, poor diet, low education, and low grip strength had stronger effects on cardiovascular disease or mortality than in HICs. Interpretation Most cardiovascular disease cases and deaths can be attributed to a small number of common, modifiable risk factors. While some factors have extensive global effects (eg, hypertension and education), others (eg, household air pollution and poor diet) vary by a country's economic level. Health policies should focus on risk factors that have the greatest effects on averting cardiovascular disease and death globally, with additional emphasis on risk factors of greatest importance in specific groups of countries. Funding Full funding sources are listed at the end of the paper (see Acknowledgments).

Some studies, mainly from high-income countries (HICs), report that women receive less care (investigations and treatments) for cardiovascular disease than do men and might have a higher risk of death. However, very few studies systematically report risk factors, use of primary or secondary prevention medications, incidence of cardiovascular disease, or death in populations drawn from the community. Given that most cardiovascular disease occurs in low-income and middle-income countries (LMICs), there is a need for comprehensive information comparing treatments and outcomes between women and men in HICs, middle-income countries, and low-income countries from community-based population studies.In the Prospective Urban Rural Epidemiological study (PURE), individuals aged 35-70 years from urban and rural communities in 27 countries were considered for inclusion. We recorded information on participants' sociodemographic characteristics, risk factors, medication use, cardiac investigations, and interventions. 168 490 participants who enrolled in the first two of the three phases of PURE were followed up prospectively for incident cardiovascular disease and death.From Jan 6, 2005 to May 6, 2019, 202 072 individuals were recruited to the study. The mean age of women included in the study was 50·8 (SD 9·9) years compared with 51·7 (10) years for men. Participants were followed up for a median of 9·5 (IQR 8·5-10·9) years. Women had a lower cardiovascular disease risk factor burden using two different risk scores (INTERHEART and Framingham). Primary prevention strategies, such as adoption of several healthy lifestyle behaviours and use of proven medicines, were more frequent in women than men. Incidence of cardiovascular disease (4·1 [95% CI 4·0-4·2] for women vs 6·4 [6·2-6·6] for men per 1000 person-years; adjusted hazard ratio [aHR] 0·75 [95% CI 0·72-0·79]) and all-cause death (4·5 [95% CI 4·4-4·7] for women vs 7·4 [7·2-7·7] for men per 1000 person-years; aHR 0·62 [95% CI 0·60-0·65]) were also lower in women. By contrast, secondary prevention treatments, cardiac investigations, and coronary revascularisation were less frequent in women than men with coronary artery disease in all groups of countries. Despite this, women had lower risk of recurrent cardiovascular disease events (20·0 [95% CI 18·2-21·7] versus 27·7 [95% CI 25·6-29·8] per 1000 person-years in men, adjusted hazard ratio 0·73 [95% CI 0·64-0·83]) and women had lower 30-day mortality after a new cardiovascular disease event compared with men (22% in women versus 28% in men; p0·0001). Differences between women and men in treatments and outcomes were more marked in LMICs with little differences in HICs in those with or without previous cardiovascular disease.Treatments for cardiovascular disease are more common in women than men in primary prevention, but the reverse is seen in secondary prevention. However, consistently better outcomes are observed in women than in men, both in those with and without previous cardiovascular disease. Improving cardiovascular disease prevention and treatment, especially in LMICs, should be vigorously pursued in both women and men.Full funding sources are listed at the end of the paper (see Acknowledgments).

Digital, Background: Eggs are a rich source of essential nutrients, but they are also a source of dietary cholesterol. Therefore, some guidelines recommend limiting egg consumption. However, there is contradictory evidence on the impact of eggs on diseases, largely based on studies conducted in high-income countries. Objectives: Our aim was to assess the association of egg consumption with blood lipids, cardiovascular disease (CVD), and mortality in large global studies involving populations from low-, middle-, and high-income countries. Methods: We studied 146,011 individuals from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study. Egg consumption was recorded using country-specific validated FFQs. We also studied 31,544 patients with vascular disease in 2 multinational prospective studies: ONTARGET (Ongoing Telmisartan Alone and in Combination with Ramipril Global End Point Trial) and TRANSCEND (Telmisartan Randomized Assessment Study in ACEI Intolerant Subjects with Cardiovascular Disease). We calculated HRs using multivariable Cox frailty models with random intercepts to account for clustering by study center separately within each study. Results: In the PURE study, we recorded 14,700 composite events (8932 deaths and 8477 CVD events). In the PURE study, after excluding those with history of CVD, higher intake of egg (≥7 egg/wk compared with, Ciencias Médicas y de la Salud

Digital, Exposure to air pollution has been linked to elevated blood pressure (BP) and hypertension, but most research has focused on short-term (hours, days, or months) exposures at relatively low concentrations. We examined the associations between long-term (3-year average) concentrations of outdoor PM2.5 and household air pollution (HAP) from cooking with solid fuels with BP and hypertension in the Prospective Urban and Rural Epidemiology (PURE) study. Outdoor PM2.5 exposures were estimated at year of enrollment for 137,809 adults aged 35–70 years from 640 urban and rural communities in 21 countries using satellite and ground-based methods. Primary use of solid fuel for cooking was used as an indicator of HAP exposure, with analyses restricted to rural participants (n = 43,313) in 27 study centers in 10 countries. BP was measured following a standardized procedure and associations with air pollution examined with mixed-effect regression models, after adjustment for a comprehensive set of potential confounding factors. Baseline outdoor PM2.5 exposure ranged from 3 to 97 μg/m3 across study communities and was associated with an increased odds ratio (OR) of 1.04 (95% CI: 1.01, 1.07) for hypertension, per 10 μg/m3 increase in concentration. This association demonstrated non-linearity and was strongest for the fourth (PM2.5 > 62 μg/m3) compared to the first (PM2.5 < 14 μg/m3) quartiles (OR = 1.36, 95% CI: 1.10, 1.69). Similar non-linear patterns were observed for systolic BP (β = 2.15 mmHg, 95% CI: −0.59, 4.89) and diastolic BP (β = 1.35, 95% CI: −0.20, 2.89), while there was no overall increase in ORs across the full exposure distribution. Individuals who used solid fuels for cooking had lower BP measures compared to clean fuel users (e.g. 34% of solid fuels users compared to 42% of clean fuel users had hypertension), and even in fully adjusted models had slightly decreased odds of hypertension (OR = 0.93; 95% CI: 0.88, 0.99) and reductions in systolic (−0.51 mmHg; 95% CI: −0.99, −0.03) and diastolic (−0.46 mmHg; 95% CI: −0.75, −0.18) BP. In this large international multi-center study, chronic exposures to outdoor PM2.5 was associated with increased BP and hypertension while there were small inverse associations with HAP., Ciencias Médicas y de la Salud

ObjectiveTo evaluate the joint association of sodium and potassium urinary excretion (as surrogate measures of intake) with cardiovascular events and mortality, in the context of current World Health Organization recommendations for daily intake (3.5 g potassium) in adults.DesignInternational prospective cohort study.Setting18 high, middle, and low income countries, sampled from urban and rural communities.Participants103 570 people who provided morning fasting urine samples.Main outcome measuresAssociation of estimated 24 hour urinary sodium and potassium excretion (surrogates for intake) with all cause mortality and major cardiovascular events, using multivariable Cox regression. A six category variable for joint sodium and potassium was generated: sodium excretion (low (5 g/day) sodium intakes) by potassium excretion (greater/equal or less than median 2.1 g/day).ResultsMean estimated sodium and potassium urinary excretion were 4.93 g/day and 2.12 g/day, respectively. After a median follow-up of 8.2 years, 7884 (6.1%) participants had died or experienced a major cardiovascular event. Increasing urinary sodium excretion was positively associated with increasing potassium excretion (unadjusted r=0.34), and only 0.002% had a concomitant urinary excretion of 3.5 g/day of potassium. A J-shaped association was observed of sodium excretion and inverse association of potassium excretion with death and cardiovascular events. For joint sodium and potassium excretion categories, the lowest risk of death and cardiovascular events occurred in the group with moderate sodium excretion (3-5 g/day) and higher potassium excretion (21.9% of cohort). Compared with this reference group, the combinations of low potassium with low sodium excretion (hazard ratio 1.23, 1.11 to 1.37; 7.4% of cohort) and low potassium with high sodium excretion (1.21, 1.11 to 1.32; 13.8% of cohort) were associated with the highest risk, followed by low sodium excretion (1.19, 1.02 to 1.38; 3.3% of cohort) and high sodium excretion (1.10, 1.02 to 1.18; 29.6% of cohort) among those with potassium excretion greater than the median. Higher potassium excretion attenuated the increased cardiovascular risk associated with high sodium excretion (P for interaction=0.007).ConclusionsThese findings suggest that the simultaneous target of low sodium intake (3.5 g/day) is extremely uncommon. Combined moderate sodium intake (3-5 g/day) with high potassium intake is associated with the lowest risk of mortality and cardiovascular events.