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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.

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.

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.