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Additional file 1.

Additional file 6: Supplement 6. Trial registration data of the LIGHT-ACD trial.

Additional file 3: Supplement 3. Example of CDSS recommendation.

Additional file 1: Supplement 1. Stratification factors for each stage in site randomization of LIGHT trial.

Additional file 4: Supplement 4. Specifications of guideline-based antihypertensive treatment.

BackgroundReports on medium and long-term sequelae of SARS-CoV-2 infections largely lack quantification of incidence and relative risk. We describe the rationale and methods of the Innovative Support for Patients with SARS-CoV-2 Registry (INSPIRE) that combines patient-reported outcomes with data from digital health records to understand predictors and impacts of SARS-CoV-2 infection.MethodsINSPIRE is a prospective, multicenter, longitudinal study of individuals with symptoms of SARS-CoV-2 infection in eight regions across the US. Adults are eligible for enrollment if they are fluent in English or Spanish, reported symptoms suggestive of acute SARS-CoV-2 infection, and if they are within 42 days of having a SARS-CoV-2 viral test (i.e., nucleic acid amplification test or antigen test), regardless of test results. Recruitment occurs in-person, by phone or email, and through online advertisement. A secure online platform is used to facilitate the collation of consent-related materials, digital health records, and responses to self-administered surveys. Participants are followed for up to 18 months, with patient-reported outcomes collected every three months via survey and linked to concurrent digital health data; follow-up includes no in-person involvement. Our planned enrollment is 4,800 participants, including 2,400 SARS-CoV-2 positive and 2,400 SARS-CoV-2 negative participants (as a concurrent comparison group). These data will allow assessment of longitudinal outcomes from SARS-CoV-2 infection and comparison of the relative risk of outcomes in individuals with and without infection. Patient-reported outcomes include self-reported health function and status, as well as clinical outcomes including health system encounters and new diagnoses.ResultsParticipating sites obtained institutional review board approval. Enrollment and follow-up are ongoing.ConclusionsThis study will characterize medium and long-term sequelae of SARS-CoV-2 infection among a diverse population, predictors of sequelae, and their relative risk compared to persons with similar symptomatology but without SARS-CoV-2 infection. These data may inform clinical interventions for individuals with sequelae of SARS-CoV-2 infection.

Additional file 5: Supplement 5. Trial registration data of the LIGHT trial.

Additional file 2.

Additional file 2: Supplement 2. Specification of hypertension visits.

Coronavirus disease-2019 (COVID-19) is associated with systemic inflammation, endothelial activation, and multiorgan manifestations. Lipid-modulating agents may be useful in treating patients with COVID-19. These agents may inhibit viral entry by lipid raft disruption or ameliorate the inflammatory response and endothelial activation. In addition, dyslipidemia with lower high-density lipoprotein cholesterol and higher triglyceride levels portend worse outcomes in patients with COVID-19. Upon a systematic search, 40 randomized controlled trials (RCTs) with lipid-modulating agents were identified, including 17 statin trials, 14 omega-3 fatty acids RCTs, 3 fibrate RCTs, 5 niacin RCTs, and 1 dalcetrapib RCT for the management or prevention of COVID-19. From these 40 RCTs, only 2 have reported preliminary results, and most others are ongoing. This paper summarizes the ongoing or completed RCTs of lipid-modulating agents in COVID-19 and the implications of these trials for patient management.

[Figure: see text].

BACKGROUND: After hospitalization for acute myocardial infarction (AMI), older adults may be at increased risk for falls due to deconditioning, new medications, and worsening health status. Our primary objective was to identify risk factors for falls after AMI hospitalization among adults over age 75. METHODS: We used data from the Comprehensive Evaluation of Risk Factors in Older Patients with AMI (SILVER-AMI) study, a prospective cohort study of 3,041 adults age 75 and older hospitalized with acute myocardial infarction at 94 community and academic medical centers across the United States. In-person interviews and physical assessments, as well as medical record review, were performed to collect demographic, clinical, functional, and psychosocial data. Falls were self-reported in telephone interviews and medically serious falls (those associated with emergency department use or hospitalization) were determined by medical record adjudication. Backward selection was used to identify predictors of fall risk in logistic regression analysis. RESULTS: 554 (21.6%) participants reported a fall and 191 (6.4%) had a medically serious fall within six months of discharge. Factors independently associated with self-reported falls included impaired mobility, prior fall history, longer hospital stay, visual impairment, and weak grip. Factors independently associated with medically serious falls included older age, polypharmacy, impaired functional mobility, prior fall history, and living alone. CONCLUSIONS: Among older patients hospitalized for AMI, falls are common in the six months following discharge and associated with demographic, functional, and clinical factors that are readily identifiable. Fall risk should be considered in post-AMI clinical decision making and interventions to prevent falls should be evaluated.

Intraoperative data may improve models predicting postoperative events. We evaluated the effect of incorporating intraoperative variables to the existing preoperative model on the predictive performance of the model for coronary artery bypass graft.We analyzed 378 572 isolated coronary artery bypass graft cases performed across 1083 centers, using the national Society of Thoracic Surgeons Adult Cardiac Surgery Database between 2014 and 2016. Outcomes were operative mortality, 5 postoperative complications, and composite representation of all events. We fitted models by logistic regression or extreme gradient boosting (XGBoost). For each modeling approach, we used preoperative only, intraoperative only, or pre+intraoperative variables. We developed 84 models with unique combinations of the 3 variable sets, 2 variable selection methods, 2 modeling approaches, and 7 outcomes. Each model was tested in 20 iterations of 70:30 stratified random splitting into development/testing samples. Model performances were evaluated on the testing dataset using the C statistic, area under the precision-recall curve, and calibration metrics, including the Brier score.The mean patient age was 65.3 years, and 24.7% were women. Operative mortality, excluding intraoperative death, occurred in 1.9%. In all outcomes, models that considered pre+intraoperative variables demonstrated significantly improved Brier score and area under the precision-recall curve compared with models considering pre or intraoperative variables alone. XGBoost without external variable selection had the best C statistics, Brier score, and area under the precision-recall curve values in 4 of the 7 outcomes (mortality, renal failure, prolonged ventilation, and composite) compared with logistic regression models with or without variable selection. Based on the calibration plots, risk restratification for mortality showed that the logistic regression model underestimated the risk in 11 114 patients (9.8%) and overestimated in 12 005 patients (10.6%). In contrast, the XGBoost model underestimated the risk in 7218 patients (6.4%) and overestimated in 0 patients (0%).In isolated coronary artery bypass graft, adding intraoperative variables to preoperative variables resulted in improved predictions of all 7 outcomes. Risk models based on XGBoost may provide a better prediction of adverse events to guide clinical care.

IMPORTANCE: Short-term outcomes after acute myocardial infarction (AMI) have improved, but little is known about longer-term outcomes. OBJECTIVE: To evaluate trends in 10-year all-cause mortality and hospitalization for recurrent AMI by demographic subgroups and examine the association between recurrence and mortality. DESIGN, SETTING, AND PARTICIPANTS: Medicare fee-for-service beneficiaries who survived after AMI from 1995 to 2019. Subgroups were defined by age, sex, race, dual Medicare-Medicaid–eligible status, and residence in health priority areas (geographic areas with persistently high adjusted mortality and hospitalization rates). Data were analyzed from October 2020 to February 2022. EXPOSURE: Medicare fee-for-service beneficiaries who survived an AMI. MAIN OUTCOMES AND MEASURES: Ten-year all-cause mortality and hospitalization for recurrent AMI, beginning 30 days from the index AMI admission. RESULTS: Of an included 3 982 266 AMI survivors, 1 952 450 (49.0%) were female, and the mean (SD) age was 78.0 (7.4) years. Ten-year mortality and recurrent AMI rates were 72.7% (95% CI, 72.6-72.7) and 27.1% (95% CI, 27.0-27.2), respectively. Adjusted annual reductions were 1.5% (95% CI, 1.4-1.5) for mortality and 2.7% (95% CI, 2.6-2.7) for recurrence. In subgroup analyses balancing patient characteristics, hazard ratios (HRs) for mortality and recurrence were 1.13 (95% CI, 1.12-1.13) and 1.07 (95% CI, 1.06-1.07), respectively, for men vs women; 1.05 (95% CI, 1.05-1.06) and 1.08 (95% CI, 1.07-1.09) for Black vs White patients; 0.96 (95% CI, 0.95-0.96) and 1.00 (95% CI, 1.00-1.01) for other race (including American Indian and Alaska Native, Asian, Hispanic, other race or ethnicity, and unreported) vs White patients; 1.24 (95% CI, 1.24-1.24) and 1.21 (95% CI, 1.20-1.21) for dual Medicare-Medicaid–eligible vs non–dual Medicare-Medicaid–eligible patients; and 1.06 (95% CI, 1.06-1.07) and 1.00 (95% CI, 1.00-1.01) for patients in health priority areas vs other areas. For patients hospitalized in 2007 to 2009, the last 3 years for which full 10-year follow-up data were available, 10-year mortality risk was 13.9% lower than for those hospitalized in 1995 to 1997 (adjusted HR, 0.86; 95% CI, 0.85-0.87) and 10-year recurrence risk was 22.5% lower (adjusted HR, 0.77; 95% CI, 0.76-0.78). Mortality within 10 years after the initial AMI was higher for patients with a recurrent AMI (80.6%; 95% CI, 80.5-80.7) vs those without recurrence (72.4%; 95% CI, 72.3-72.5). CONCLUSIONS AND RELEVANCE: In this study, 10-year mortality and hospitalization for recurrence rates improved over the last decades for patients who survived the acute period of AMI. There were marked differences in outcomes and temporal trends across demographic subgroups, emphasizing the urgent need for prioritization of efforts to reduce inequities in long-term outcomes.

In this Article, author Marquis P. Vawter was missing from the Genome Aggregation Database Consortium list. They are associated with the affiliation: ‘Department of Psychiatry & Human Behavior, University of California Irvine, Irvine, CA, USA’, and contributed to the generation of the primary data incorporated into the gnomAD resource. In addition, in the legend to Fig. 1, ‘ten’ should have been ‘seven’ in the sentence: “a, Uniform manifold approximation and projection (UMAP)46,47 plot depicting the ancestral diversity of all individuals in gnomAD, using seven principal components.” The original Article has been corrected online.

Background Many communities have implemented systems of regionalized care to improve access to timely care for patients with ST-segment-elevation myocardial infarction. However, patients who are ultimately diagnosed with non-ST-segment-elevation myocardial infarctions (NSTEMIs) may also be affected, and the impact of regionalization programs on NSTEMI treatment and outcomes is unknown. We set out to determine the effects of ST-segment-elevation myocardial infarction regionalization schemes on treatment and outcomes of patients diagnosed with NSTEMIs. Methods and Results The cohort included all patients receiving care in emergency departments diagnosed with an NSTEMI at all nonfederal hospitals in California from January 1, 2005 to September 30, 2015. Data were analyzed using a difference-in-differences approach. The main outcomes were 1-year mortality and angiography within 3days of the index admission. A total of 293589 patients with NSTEMIs received care in regionalized and nonregionalized communities. Over the study period, rates of early angiography increased by 0.5 and mortality decreased by 0.9 percentage points per year among the overall population (95% CI, 0.4-0.6 and -1.0 to -0.8, respectively). Regionalization was not associated with early angiography (-0.5%; 95% CI, -1.1 to 0.1) or death (0.2%; 95% CI, -0.3 to 0.8). Conclusions ST-segment-elevation myocardial infarction regionalization programs were not statistically associated with changes in guideline-recommended early angiography or changes in risk of death for patients with NSTEMI. Increases in the proportion of patients with NSTEMI who underwent guideline-directed angiography and decreases in risk of mortality were accounted for by secular trends unrelated to regionalization policies.

Supplementary Material for this article is available at https://www.ahajournals.org/doi/suppl/10.1161/JAHA.120.016932 17 USC 105 interim-entered record; under review. 17 USC 105 interim-entered record; under review. The article of record as published may be found at https://doi.org/10.1161/JAHA.120.016932 Background: Many communities have implemented systems of regionalized care to improve access to timely care for patients with ST‐segment–elevation myocardial infarction. However, patients who are ultimately diagnosed with non–ST‐segment–elevation myocardial infarctions (NSTEMIs) may also be affected, and the impact of regionalization programs on NSTEMI treatment and outcomes is unknown. We set out to determine the effects of ST‐segment–elevation myocardial infarction regionalization schemes on treatment and outcomes of patients diagnosed with NSTEMIs. Methods and Results: The cohort included all patients receiving care in emergency departments diagnosed with an NSTEMI at all nonfederal hospitals in California from January 1, 2005 to September 30, 2015. Data were analyzed using a difference‐in‐differences approach. The main outcomes were 1‐year mortality and angiography within 3 days of the index admission. A total of 293 589 patients with NSTEMIs received care in regionalized and nonregionalized communities. Over the study period, rates of early angiography increased by 0.5 and mortality decreased by 0.9 percentage points per year among the overall population (95% CI, 0.4–0.6 and −1.0 to −0.8, respectively). Regionalization was not associated with early angiography (−0.5%; 95% CI, −1.1 to 0.1) or death (0.2%; 95% CI, −0.3 to 0.8). Conclusions: ST‐segment–elevation myocardial infarction regionalization programs were not statistically associated with changes in guideline‐recommended early angiography or changes in risk of death for patients with NSTEMI. Increases in the proportion of patients with NSTEMI who underwent guideline‐directed angiography and decreases in risk of mortality were accounted for by secular trends unrelated to regionalization policies. Research reported in this publication was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award No. R01HL134182 for Drs Hsia and Montoy, and R01HL114822 for Drs Hsia and Shen.

ObjectivesThis study sought to evaluate the association and burden of coronary artery calcium (CAC) with long-term, cause-specific mortality across the spectrum of baseline risk.BackgroundAlthough CAC is a known predictor of short-term, all-cause mortality, data on long-term and cause-specific mortality are inadequate.MethodsThe CAC Consortium cohort is a multicenter cohort of 66,636 participants without coronary heart disease (CHD) who underwent CAC testing. The following risk factors (RFs) were considered: 1) current cigarette smoking; 2) dyslipidemia; 3) diabetes mellitus; 4) hypertension; and 5) family history of CHD.ResultsDuring the 12.5-years median follow-up, 3,158 (4.7%) deaths occurred; 32% were cardiovascular disease (CVD) deaths. Participants with CAC scores ≥400 had a significantly increased risk for CHD and CVD mortality (hazard ratio [HR]: 5.44; 95% confidence interval [CI]: 3.88 to 7.62; and HR: 4.15; 95% CI: 3.29 to 5.22, respectively) compared with CAC of 0. Participants with ≥3 RFs had a smaller increased risk for CHD and CVD mortality (HR: 2.09; 95% CI: 1.52 to 2.85; and HR: 1.84; 95% CI: 1.46 to 2.31, respectively) compared with those without RFs. Across RF strata, CAC added prognostic information. For example, participants without RFs but with CAC ≥400 had significantly higher all-cause, non-CVD, CVD, and CHD mortality rates compared with participants with ≥3 RFs and CAC of 0.ConclusionsAcross the spectrum of RF burden, a higher CAC score was strongly associated with long-term, all-cause mortality and a greater proportion of deaths due to CVD and CHD. Absence of CAC identified people with a low risk over 12 years of follow-up, with most deaths being non-CVD in nature, regardless of RF burden.

Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis. In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy. Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease. Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.

Supplemental material, Supplementary_File for Where Skilled Nursing Facility Residents Get Acute Care: Is the Emergency Department the Medical Home? by Arjun K. Venkatesh, Cameron J. Gettel, Hao Mei, Shih-Chuan Chou, Craig Rothenberg, Shu-Ling Liu, Gail D’Onofrio, ZhenQiu Lin and Harlan M. Krumholz in Journal of Applied Gerontology

Additional file 1: Figure A1. Monthly cohort definition for AMI, HF or Pneumonia Readmissions and Observation Stays (Pg.2). Figure A2. Hierarchy for multiple post-discharge care events (Pg. 2). Table A1. Cumulative numbers and percentages of final action inpatient claims uploaded to the IDR for all conditions with a discharge date in January 2013 and July 2013 (as of December 2014) (Pg.3). Figure A3: Modeling approach (Pg.3). Figure A4. Timing of calculating monthly outcomes (Pg.4). Table A2. Final model specification for prediction of number of admissions, readmission rate, and observation-stay rate in AMI cohort (Pg.4). Table A3: Specifications of the final real-time reporting models for Heart failure and pneumonia (Pg.6). Table A4: Results of look-back validation where we compare the rates estimated (for the months July 2016 through December 2016) in February 2017 using RTR models with the final rates later observed using data downloaded from the IDR in February 2018 for AMI, HF and Pneumonia (Pg.7). Figure A5. Prediction and look-back validation for heart failure admission, readmission and observation stays (July 2016–December 2016) (Pg.8). Figure A6. Prediction and look-back validation for pneumonia admission, readmission and observation stays (July 2016–December 2016 (Pg.9).

Coronavirus disease 2019 (COVID-19), currently a worldwide pandemic, is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The suspected contribution of thrombotic events to morbidity and mortality in COVID-19 patients has prompted a search for novel potential options for preventing COVID-19-associated thrombotic disease. In this article by the Global COVID-19 Thrombosis Collaborative Group, we describe novel dosing approaches for commonly used antithrombotic agents (especially heparin-based regimens) and the potential use of less widely used antithrombotic drugs in the absence of confirmed thrombosis. Although these therapies may have direct antithrombotic effects, other mechanisms of action, including anti-inflammatory or antiviral effects, have been postulated. Based on survey results from this group of authors, we suggest research priorities for specific agents and subgroups of patients with COVID-19. Further, we review other agents, including immunomodulators, that may have antithrombotic properties. It is our hope that the present document will encourage and stimulate future prospective studies and randomized trials to study the safety, efficacy, and optimal use of these agents for prevention or management of thrombosis in COVID-19.

Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis. In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy. Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease. Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic. (J Am Coll Cardiol 2020;75:2950-73) (c) 2020 by the American College of Cardiology Foundation.

BACKGROUND:Uncertainty remains about the optimal monotherapy for hypertension, with current guidelines recommending any primary agent among the first-line drug classes thiazide or thiazide-like diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, dihydropyridine calcium channel blockers, and non-dihydropyridine calcium channel blockers, in the absence of comorbid indications. Randomised trials have not further refined this choice. METHODS:We developed a comprehensive framework for real-world evidence that enables comparative effectiveness and safety evaluation across many drugs and outcomes from observational data encompassing millions of patients, while minimising inherent bias. Using this framework, we did a systematic, large-scale study under a new-user cohort design to estimate the relative risks of three primary (acute myocardial infarction, hospitalisation for heart failure, and stroke) and six secondary effectiveness and 46 safety outcomes comparing all first-line classes across a global network of six administrative claims and three electronic health record databases. The framework addressed residual confounding, publication bias, and p-hacking using large-scale propensity adjustment, a large set of control outcomes, and full disclosure of hypotheses tested. FINDINGS:Using 4·9 million patients, we generated 22 000 calibrated, propensity-score-adjusted hazard ratios (HRs) comparing all classes and outcomes across databases. Most estimates revealed no effectiveness differences between classes; however, thiazide or thiazide-like diuretics showed better primary effectiveness than angiotensin-converting enzyme inhibitors: acute myocardial infarction (HR 0·84, 95% CI 0·75-0·95), hospitalisation for heart failure (0·83, 0·74-0·95), and stroke (0·83, 0·74-0·95) risk while on initial treatment. Safety profiles also favoured thiazide or thiazide-like diuretics over angiotensin-converting enzyme inhibitors. The non-dihydropyridine calcium channel blockers were significantly inferior to the other four classes. INTERPRETATION:This comprehensive framework introduces a new way of doing observational health-care science at scale. The approach supports equivalence between drug classes for initiating monotherapy for hypertension-in keeping with current guidelines, with the exception of thiazide or thiazide-like diuretics superiority to angiotensin-converting enzyme inhibitors and the inferiority of non-dihydropyridine calcium channel blockers. FUNDING:US National Science Foundation, US National Institutes of Health, Janssen Research & Development, IQVIA, South Korean Ministry of Health & Welfare, Australian National Health and Medical Research Council.

BACKGROUND: Among older adults (age ≥75) hospitalized for acute myocardial infarction, acute kidney injury after coronary angiography is common. Aging-related conditions may independently predict acute kidney injury, but have not yet been analyzed in large acute myocardial infarction cohorts. METHODS: We analyzed data from 2212 participants age ≥75 in the SILVER-AMI study who underwent coronary angiography. Acute kidney injury was defined using KDIGO criteria (serum Cr increase ≥0.3 mg/dL from baseline or ≥1.5 times baseline). We analyzed the associations of traditional acute kidney injury risk factors and aging-related conditions (ADL impairment, prior falls, cachexia, low physical activity) with acute kidney injury, and then performed logistic regression to identify independent predictors. RESULTS: Participants’ mean age was 81.3 years, 45.2% were female, and 9.5% were nonwhite; 421 (19.0%) experienced acute kidney injury. Comorbid diseases and aging-related conditions were both more common among individuals experiencing acute kidney injury. However, after multivariable adjustment, no aging-related conditions were retained. There were 11 risk factors in the final model; the strongest were heart failure on presentation (OR 1.91, 95% CI 1.41-2.59), BMI >30 (vs. BMI 18-25: OR 1.75, 95% CI 1.27-2.42), and nonwhite race (OR 1.65, 95% CI 1.16-2.33). The final model achieved an AUC of 0.72 and was well calibrated (Hosmer-Lemeshow P=0.50). Acute kidney injury was independently associated with 6 month mortality (OR 1.98, 95% CI 1.36-2.88) but not readmission (OR 1.26, 95% CI 0.98-1.61). CONCLUSIONS: Acute kidney injury is common among older adults with acute myocardial infarction undergoing coronary angiography. Predictors largely mirrored those in previous studies of younger individuals, which suggests that geriatric conditions mediate their influence through other risk factors.

BackgroundThe relative prevalence and clinical importance of monogenic mutations related to familial hypercholesterolemia and of high polygenic score (cumulative impact of many common variants) pathways for early-onset myocardial infarction remain uncertain. Whole-genome sequencing enables simultaneous ascertainment of both monogenic mutations and polygenic score for each individual.MethodsWe performed deep-coverage whole-genome sequencing of 2081 patients from 4 racial subgroups hospitalized in the United States with early-onset myocardial infarction (age ≤55 years) recruited with a 2:1 female-to-male enrollment design. We compared these genomes with those of 3761 population-based control subjects. We first identified individuals with a rare, monogenic mutation related to familial hypercholesterolemia. Second, we calculated a recently developed polygenic score of 6.6 million common DNA variants to quantify the cumulative susceptibility conferred by common variants. We defined high polygenic score as the top 5% of the control distribution because this cutoff has previously been shown to confer similar risk to that of familial hypercholesterolemia mutations.ResultsThe mean age of the 2081 patients presenting with early-onset myocardial infarction was 48 years, and 66% were female. A familial hypercholesterolemia mutation was present in 36 of these patients (1.7%) and was associated with a 3.8-fold (95% CI, 2.1-6.8; P3-fold increased odds of early-onset myocardial infarction. However, high polygenic score has a 10-fold higher prevalence among patients presents with early-onset myocardial infarction.Clinical trial registrationURL: https://www.clinicaltrials.gov . Unique identifier: NCT00597922.

Upstream open reading frames (uORFs) are important tissue-specific cis-regulators of protein translation. Although isolated case reports have shown that variants that create or disrupt uORFs can cause disease, genetic sequencing approaches typically focus on protein-coding regions and ignore these variants. Here, we describe a systematic genome-wide study of variants that create and disrupt human uORFs, and explore their role in human disease using 15,708 whole genome sequences collected by the Genome Aggregation Database (gnomAD) project. We show that 14,897 variants that create new start codons upstream of the canonical coding sequence (CDS), and 2,406 variants disrupting the stop site of existing uORFs, are under strong negative selection. Furthermore, variants creating uORFs that overlap the CDS show signals of selection equivalent to coding loss-of-function variants, and uORF-perturbing variants are under strong selection when arising upstream of known disease genes and genes intolerant to loss-of-function variants. Finally, we identify specific genes where perturbation of uORFs is likely to represent an important disease mechanism, and report a novel uORF frameshift variant upstream of NF2 in families with neurofibromatosis. Our results highlight uORF-perturbing variants as an important and under-recognised functional class that can contribute to penetrant human disease, and demonstrate the power of large-scale population sequencing data to study the deleteriousness of specific classes of non-coding variants.

Publisher's version (útgefin grein), Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after 'recalibration', a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied. Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at 'high' 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29-39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22-24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44-51 such individuals using original algorithms, in contrast to 37-39 individuals with recalibrated algorithms. Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need., The work of the co-ordinating centre was funded by the UK Medical Research Council (G0800270), British Heart Foundation (SP/09/ 002), British Heart Foundation Cambridge Cardiovascular Centre of Excellence, UK National Institute for Health Research Cambridge Biomedical Research Centre, European Research Council (268834), and European Commission Framework Programme 7 (HEALTH-F2-2012-279233). The Emerging Risk Factor Collaboration’s website https://www.phpc.cam.ac.uk/ceu/erfc/list-of-studies/ has compiled a list provided by investigators of some of the funders of the component studies in this analysis. I.W. was supported by the Medical Research Council Unit Programme MC_UU_12023/21. M.K. is supported by the Netherlands Organization for Scientific Research (NWO) Veni grant (Veni, 91616079). J.P. is supported by Erasmus Mundus Western Balkans (ERAWEB), a project funded by the European Commission.

Cardiovascular disorders account for nearly 1 in 3 deaths in the United States. Care for these disorders are often determined during visits to acute care facilities, such as hospitals. While the length of stay in these settings represents just a small proportion of patients' lives, they account for a disproportionately large amount of decision making. To overcome this bias towards data from acute care settings, there is a need for longitudinal monitoring in patients with cardiovascular disorders. Longitudinal monitoring can provide a more comprehensive picture of patient health, allowing for more informed decision making. This work surveys the current field of sensing technologies and machine learning analytics that exist in the field of remote monitoring for cardiovascular disorders. We highlight three primary needs in the design of new smart health technologies: 1) the need for sensing technology that can track longitudinal trends in signs and symptoms of the cardiovascular disorder despite potentially infrequent, noisy, or missing data measurements; 2) the need for new analytic techniques that model data captured in a longitudinal, continual fashion to aid in the development of new risk prediction techniques and in tracking disease progression; and 3) the need for machine learning techniques that are personalized and interpretable, allowing for advancements in shared clinical decision making. We highlight these needs based upon the current state-of-the-art in smart health technologies and analytics and discuss the ample opportunities that exist in addressing all three needs in the development of smart health technologies and analytics applied to the field of cardiovascular disorders and care., Comment: 32 pages, 3 figures, to be submitted to ACM Transactions on Computing for Healthcare (HEALTH), Special Issue on Wearable Technologies for Smart Health 2019

BackgroundPhysicians "purchase" many health care services on behalf of patients yet remain largely unaware of the costs of these services. Electronic health record (EHR) cost displays may facilitate cost-conscious ordering of health services.ObjectiveTo determine whether displaying hospital lab and imaging order costs is associated with changes in the number and costs of orders placed.DesignQuasi-experimental study.ParticipantsAll patients with inpatient or observation encounters across a multi-site health system from April 2013 to October 2015.InterventionDisplay of order costs, based on Medicare fee schedules, in the EHR for 1032 lab tests and 1329 imaging tests.Main measuresOutcomes for both lab and imaging orders were (1) whether an order was placed during a hospital encounter, (2) whether an order was placed on a given patient-day, (3) number of orders placed per patient-day, and (4) cost of orders placed per patient-day.Key resultsDuring the lab and imaging study periods, there were 248,214 and 258,267 encounters, respectively. Cost display implementation was associated with a decreased odds of any lab or imaging being ordered during the encounter (lab adjusted odds ratio [AOR] = 0.97, p= .01; imaging AOR = 0.97, p&nbsp

Objective: To (1) demonstrate the implementation of a data science platform built on open-source technology within a large, academic healthcare system and (2) describe two computational healthcare applications built on such a platform. Materials and Methods: A data science platform based on several open source technologies was deployed to support real-time, big data workloads. Data acquisition workflows for Apache Storm and NiFi were developed in Java and Python to capture patient monitoring and laboratory data for downstream analytics. Results: The use of emerging data management approaches along with open-source technologies such as Hadoop can be used to create integrated data lakes to store large, real-time data sets. This infrastructure also provides a robust analytics platform where healthcare and biomedical research data can be analyzed in near real-time for precision medicine and computational healthcare use cases. Discussion: The implementation and use of integrated data science platforms offer organizations the opportunity to combine traditional data sets, including data from the electronic health record, with emerging big data sources, such as continuous patient monitoring and real-time laboratory results. These platforms can enable cost-effective and scalable analytics for the information that will be key to the delivery of precision medicine initiatives. Conclusion: Organizations that can take advantage of the technical advances found in data science platforms will have the opportunity to provide comprehensive access to healthcare data for computational healthcare and precision medicine research., Comment: 8 pages, 4 figures, 1 table

The governance of data used for biomedical research and clinical trials is an important requirement for generating accurate results. To improve the visibility of data quality and analysis, we developed TrialChain, a blockchain-based platform that can be used to validate data integrity from large, biomedical research studies. We implemented a private blockchain using the MultiChain platform and integrated it with a data science platform deployed within a large research center. An administrative web application was built with Python to manage the platform, which was built with a microservice architecture using Docker. The TrialChain platform was integrated during data acquisition into our existing data science platform. Using NiFi, data were hashed and logged within the local blockchain infrastructure. To provide public validation, the local blockchain state was periodically synchronized to the public Ethereum network. The use of a combined private/public blockchain platform allows for both public validation of results while maintaining additional security and lower cost for blockchain transactions. Original data and modifications due to downstream analysis can be logged within TrialChain and data assets or results can be rapidly validated when needed using API calls to the platform. The TrialChain platform provides a data governance solution to audit the acquisition and analysis of biomedical research data. The platform provides cryptographic assurance of data authenticity and can also be used to document data analysis.

BACKGROUND: In 2008, the National Heart, Lung, and Blood Institute convened an Implementation Science Work Group to assess evidence-based strategies for effectively implementing clinical practice guidelines. This was part of a larger effort to update existing clinical practice guidelines on cholesterol, blood pressure, and overweight/obesity. OBJECTIVES: Review evidence from the published implementation science literature and identify effective or promising strategies to enhance the adoption and implementation of clinical practice guidelines. METHODS: This systematic review was conducted on 4 critical questions, each focusing on the adoption and effectiveness of 4 intervention strategies: (1) reminders, (2) educational outreach visits, (3) audit and feedback, and (4) provider incentives. A scoping review of the Rx for Change database of systematic reviews was used to identify promising guideline implementation interventions aimed at providers. Inclusion and exclusion criteria were developed a priori for each question, and the published literature was initially searched up to 2012, and then updated with a supplemental search to 2015. Two independent reviewers screened the returned citations to identify relevant reviews and rated the quality of each included review. RESULTS: Audit and feedback and educational outreach visits were generally effective in improving both process of care (15 of 21 reviews and 12 of 13 reviews, respectively) and clinical outcomes (7 of 12 reviews and 3 of 5 reviews, respectively). Provider incentives showed mixed effectiveness for improving both process of care (3 of 4 reviews) and clinical outcomes (3 reviews equally distributed between generally effective, mixed, and generally ineffective). Reminders showed mixed effectiveness for improving process of care outcomes (27 reviews with 11 mixed and 3 generally ineffective results) and were generally ineffective for clinical outcomes (18 reviews with 6 mixed and 9 generally ineffective results). Educational outreach visits (2 of 2 reviews), reminders (3 of 4 reviews), and provider incentives (1 of 1 review) were generally effective for cost reduction. Educational outreach visits (1 of 1 review) and provider incentives (1 of 1 review) were also generally effective for cost-effectiveness outcomes. Barriers to clinician adoption or adherence to guidelines included time constraints (8 reviews/overviews); limited staffing resources (2 overviews); timing (5 reviews/overviews); clinician skepticism (5 reviews/overviews); clinician knowledge of guidelines (4 reviews/overviews); and higher age of the clinician (1 overview). Facilitating factors included guideline characteristics such as format, resources, and end-user involvement (6 reviews/overviews); involving stakeholders (5 reviews/overviews); leadership support (5 reviews/overviews); scope of implementation (5 reviews/overviews); organizational culture such as multidisciplinary teams and low-baseline adherence (9 reviews/overviews); and electronic guidelines systems (3 reviews). CONCLUSION: The strategies of audit and feedback and educational outreach visits were generally effective in improving both process of care and clinical outcomes. Reminders and provider incentives showed mixed effectiveness, or were generally ineffective. No general conclusion could be reached about cost effectiveness, because of limitations in the evidence. Important gaps exist in the evidence on effectiveness of implementation interventions, especially regarding clinical outcomes, cost effectiveness and contextual issues affecting successful implementation.

Young women with acute myocardial infarction (AMI) have higher mortality risk than similarly aged men. An adverse lipid profile is an important risk factor for cardiovascular outcomes after AMI, but little is known about whether young women with AMI have a higher-risk lipid pattern than men. We characterized sex differences in lipid profiles and treatment utilization among young adults with AMI.

Young women with acute myocardial infarction (AMI) have a higher risk of adverse outcomes than men. However, it is unclear how young women with AMI are different from young men across a spectrum of characteristics. We sought to compare young women and men at the time of AMI on six domains of demographic and clinical factors in order to determine whether they have distinct profiles.Using data from Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO), a prospective cohort study of women and men aged ⩽55 years hospitalized for AMI ( n = 3501) in the United States and Spain, we evaluated sex differences in demographics, healthcare access, cardiovascular risk and psychosocial factors, symptoms and pre-hospital delay, clinical presentation, and hospital management for AMI. The study sample included 2349 (67%) women and 1152 (33%) men with a mean age of 47 years. Young women with AMI had higher rates of cardiovascular risk factors and comorbidities than men, including diabetes, congestive heart failure, chronic obstructive pulmonary disease, renal failure, and morbid obesity. They also exhibited higher levels of depression and stress, poorer physical and mental health status, and lower quality of life at baseline. Women had more delays in presentation and presented with higher clinical risk scores on average than men; however, men presented with higher levels of cardiac biomarkers and more classic electrocardiogram findings. Women were less likely to undergo revascularization procedures during hospitalization, and women with ST segment elevation myocardial infarction were less likely to receive timely primary reperfusion.Young women with AMI represent a distinct, higher-risk population that is different from young men.

IntroductionComplex coronary artery disease (left main and three-vessel disease) carries high risks of adverse events and cost burden. However, in China, little is known about which patients are directed toward which treatment strategies and what outcomes are being achieved.Methods and analysisUsing the China PEACE (Patient-centered Evaluative Assessment of Cardiac Events) research network, this prospective study of three-Vessel Disease, the China PEACE-3VD study, has a plan to consecutively register over 4000 patients with a diagnosis of 3VD and/or left-main disease by elective coronary angiography at 24 large cardiovascular centres in China. We centrally conducted medical record abstraction and SYNTAX Score calculation for all registered patients. The sites invited patients to the prospective cohort, and conducted 1-year follow-up on major events, including cardiac events, symptoms, secondary prevention and quality of life. The estimated entire sample size of eligible patients of 4000 was determined based on both feasibility and consideration of adequate statistical precision for describing the treatment decisions, guidelines adherence and appropriateness of treatment for patients with complex coronary artery diseases. The study is designed to investigate patient, clinician and hospital factors associated with each treatment strategy (percutaneous coronary intervention, coronary artery bypass grafting or medical therapy) as well as appropriateness of treatment choice, current guideline compliance and patient-reported outcomes for patients with complex coronary artery disease in large cardiovascular centres in China, as a foundation for enhanced knowledge in the field and to assist quality improvement initiatives.Ethics and disseminationThe study protocol was approved by the ethics committee at the China National Center for Cardiovascular Diseases. Findings will be shared with participating hospitals, policymakers and the academic community, to promote quality monitoring, quality improvement and the efficient allocation, and use of coronary revascularisation procedures in China.Trial registration numberNCT01625312; Pre-results.

BackgroundGuidelines for heart failure (HF) recommend prescription of guideline-directed medical therapy before hospital discharge; some of these therapies are included in publicly reported performance measures. The burden of new medications for individual patients has not been described.Methods and resultsWe used Get With The Guidelines-HF registry data from 2008 to 2013 to characterize prescribing, indications, and contraindications for angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, β-blockers, aldosterone antagonists, hydralazine/isosorbide dinitrate, and anticoagulants. The difference between a patient's medication regimen at hospital admission and that recommended by HF quality measures at discharge was calculated. Among 158 922 patients from 271 hospitals with a primary discharge diagnosis of HF, initiation of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was indicated in 18.1% of all patients (55.5% of those eligible at discharge were not receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers at admission), β-blockers in 20.3% (50.5% of eligible), aldosterone antagonists in 24.1% (87.4% of eligible), hydralazine/isosorbide dinitrate in 8.6% (93.1% of eligible), and anticoagulants in 18.0% (58.0% of eligible). Cumulatively, 0.4% of patients were eligible for 5 new medication groups, 4.1% for 4 new medication groups, 9.4% for 3 new medication groups, 10.1% for 2 new medication groups, and 22.7% for 1 new medication group; 15.0% were not eligible for new medications because of adequate prescribing at admission; and 38.4% were not eligible for any medications recommended by HF quality measures. Compared with newly indicated medications (mean, 1.45 ± 1.23), actual new prescriptions were lower (mean, 1.16 ± 1.00).ConclusionsA quarter of patients hospitalized with HF need to start >1 medication to meet HF quality measures. Systems for addressing medication initiation and managing polypharmacy are central to HF transitional care.

Current classification schemes for acute myocardial infarction (AMI) may not accommodate the breadth of clinical phenotypes in young women.We developed a novel taxonomy among young adults (≤55 years) with AMI enrolled in the Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) study. We first classified a subset of patients (n=600) according to the Third Universal Definition of MI using a structured abstraction tool. There was heterogeneity within type 2 AMI, and 54 patients (9%; including 51 of 412 women) were unclassified. Using an inductive approach, we iteratively grouped patients with shared clinical characteristics, with the aims of developing a more inclusive taxonomy that could distinguish unique clinical phenotypes. The final VIRGO taxonomy classified 2802 study participants as follows: class 1, plaque-mediated culprit lesion (82.5% of women; 94.9% of men); class 2, obstructive coronary artery disease with supply-demand mismatch (2a: 1.4% women; 0.9% men) and without supply-demand mismatch (2b: 2.4% women; 1.1% men); class 3, nonobstructive coronary artery disease with supply-demand mismatch (3a: 4.3% women; 0.8% men) and without supply-demand mismatch (3b: 7.0% women; 1.9% men); class 4, other identifiable mechanism (spontaneous dissection, vasospasm, embolism; 1.5% women, 0.2% men); and class 5, undetermined classification (0.8% women, 0.2% men).Approximately 1 in 8 young women with AMI is unclassified by the Universal Definition of MI. We propose a more inclusive taxonomy that could serve as a framework for understanding biological disease mechanisms, therapeutic efficacy, and prognosis in this population.

It is desirable not to include planned readmissions in readmission measures because they represent deliberate, scheduled care.To develop an algorithm to identify planned readmissions, describe its performance characteristics, and identify improvements.Consensus-driven algorithm development and chart review validation study at 7 acute-care hospitals in 2 health systems.For development, all discharges qualifying for the publicly reported hospital-wide readmission measure. For validation, all qualifying same-hospital readmissions that were characterized by the algorithm as planned, and a random sampling of same-hospital readmissions that were characterized as unplanned.We calculated weighted sensitivity and specificity, and positive and negative predictive values of the algorithm (version 2.1), compared to gold standard chart review.In consultation with 27 experts, we developed an algorithm that characterizes 7.8% of readmissions as planned. For validation we reviewed 634 readmissions. The weighted sensitivity of the algorithm was 45.1% overall, 50.9% in large teaching centers and 40.2% in smaller community hospitals. The weighted specificity was 95.9%, positive predictive value was 51.6%, and negative predictive value was 94.7%. We identified 4 minor changes to improve algorithm performance. The revised algorithm had a weighted sensitivity 49.8% (57.1% at large hospitals), weighted specificity 96.5%, positive predictive value 58.7%, and negative predictive value 94.5%. Positive predictive value was poor for the 2 most common potentially planned procedures: diagnostic cardiac catheterization (25%) and procedures involving cardiac devices (33%).An administrative claims-based algorithm to identify planned readmissions is feasible and can facilitate public reporting of primarily unplanned readmissions.

Despite the excess risk of mortality in young women (≤55 years of age) after acute myocardial infarction (AMI), little is known about young women's health status (symptoms, functioning, quality of life) during the first year of recovery after an AMI. We examined gender differences in health status over time from baseline to 12 months after AMI.A total of 3501 AMI patients (67% women) 18 to 55 years of age were enrolled from 103 US and 24 Spanish hospitals. Data were obtained by medical record abstraction and patient interviews at baseline hospitalization and 1 and 12 months after AMI. Health status was measured by generic (Short Form-12) and disease-specific (Seattle Angina Questionnaire) measures. We compared health status scores at all 3 time points and used longitudinal linear mixed-effects analyses to examine the independent effect of gender, adjusting for time and selected covariates. Women had significantly lower health status scores than men at each assessment (all P values0.0001). After adjustment for time and all covariates, women had Short Form-12 physical/mental summary scores that were -0.96 (95% confidence interval [CI], -1.59 to -0.32) and -2.36 points (95% CI, -2.99 to -1.73) lower than those of men, as well as worse Seattle Angina Questionnaire physical limitations (-2.44 points lower; 95% CI, -3.53 to -1.34), more angina (-1.03 points lower; 95% CI, -1.98 to -0.07), and poorer quality of life (-3.51 points lower; 95% CI, -4.80 to -2.22).Although both genders recover similarly after AMI, women have poorer scores than men on all health status measures, a difference that persisted throughout the entire year after discharge.

Results from the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) trial, announced in January 2008, demonstrated that ezetimibe use lowered cholesterol levels but did not slow the progression of atherosclerosis.To examine the association of this announcement with national patterns of ezetimibe prescribing, including medication initiation and discontinuation, as well as predictors of use.Retrospective analysis of a national sample of adults 18 years or older who were continuously enrolled in plans of a large US pharmacy benefit manager from 2007 to 2010.Lipid-lowering therapy prescription claims were categorized as ezetimibe-containing treatments or any other lipid-lowering agent. Initiation was defined as an ezetimibe claim without another in the prior 180 days; discontinuation, as an ezetimibe claim without another in the subsequent 180 days.From 2007 to 2010, 29.1% of the 10,597,296 continuously eligible adults obtained at least 1 lipid-lowering agent prescription. Among these adults, 17.8% were prescribed ezetimibe and 95.3% another lipid-lowering agent, predominantly statins. Ezetimibe use peaked in January 2008, when 2.5% of all adults were ezetimibe users, but declined to 1.8% by December 2010. The ENHANCE trial announcement was associated with a nonsignificant 0.16% fewer monthly ezetimibe users (P = .11) but a significant 0.14% more monthly monotherapy users and 0.30% fewer users of ezetimibe concomitant with other lipid-lowering agents (both P = .01). The ENHANCE trial was also associated with 0.44% fewer monthly ezetimibe initiations (P = .002) and 10.4% more monthly ezetimibe discontinuations (P .001), particularly of ezetimibe monotherapy for both. More than half of adults who initiated ezetimibe use did so without first being prescribed another lipid-lowering agent, both before (50%-60%) and after (60%-70%) the trial. Those aged 50 to 64 years and those living in the East South Central US Census division were both more likely to initiate and less likely to discontinue ezetimibe after the ENHANCE trial.After announcement of the results of the ENHANCE trial, nearly 2% of all continuously enrolled adult beneficiaries within a large US pharmacy benefit manager used ezetimibe, although ezetimibe initiations declined and discontinuations increased.

BackgroundPrior claims analyses suggest that the use of intravenous inotropic therapy for patients hospitalized with heart failure varies substantially by hospital. Whether differences in the clinical characteristics of the patients explain observed differences in the use of inotropic therapy is not known.Methods and resultsWe sought to characterize institutional variation in inotrope use among patients hospitalized with heart failure before and after accounting for clinical factors of patients. Hierarchical generalized linear regression models estimated risk-standardized hospital-level rates of inotrope use within 209 hospitals participating in Get With The Guidelines-Heart Failure (GWTG-HF) registry between 2005 and 2011. The association between risk-standardized rates of inotrope use and clinical outcomes was determined. Overall, an inotropic agent was administered in 7691 of 126 564 (6.1%) heart failure hospitalizations: dobutamine 43%, dopamine 24%, milrinone 17%, or a combination 16%. Patterns of inotrope use were stable during the 7-year study period. Use of inotropes varied significantly between hospitals even after accounting for patient and hospital characteristics (median risk-standardized hospital rate, 5.9%; interquartile range, 3.7%-8.6%; range, 1.3%-32.9%). After adjusting for case-mix and hospital structural differences, model intraclass correlation indicated that 21% of the observed variation in inotrope use was potentially attributable to random hospital effects (ie, institutional preferences). Hospitals with higher risk-standardized inotrope use had modestly longer risk-standardized length of stay (P=0.005) but had no difference in risk-standardized inpatient mortality (P=0.12).ConclusionsUse of intravenous inotropic agents during hospitalization for heart failure varies significantly among US hospitals even after accounting for patient and hospital factors.

Objectives. We sought to 1) determine the proportion of appropriate elderly patients admitted to the hospital with unstable angina who are treated with aspirin and heparin; 2) identify patient factors associated with the Agency for Health Care Policy and Research (AHCPR) guideline-based use of aspirin and heparin; and 3) compare practice patterns and patient outcomes before and after publication of the AHCPR guidelines.Background. Improving the care of patients with unstable angina may provide immediate opportunities to mitigate the adverse consequences of unstable angina. However, despite the importance of this diagnosis, there is a paucity of information on the patterns of treatment and outcomes across diverse sites and recent trends in practice that have occurred, especially since the publication of the AHCPR practice guidelines.Methods. We performed a retrospective cohort study using data created from medical charts and administrative files. The sample included 300 consecutive patients admitted to one of three Connecticut hospitals in the period 1993 to 1994 and 150 consecutive patients admitted in 1995 with a principal discharge diagnosis of unstable angina or chest pain.Results. Of the 384 patients ≥65 years old who had no contraindications to aspirin on hospital admission, 276 (72%) received it. Of the 369 patients ≥65 years old who had no contraindications to heparin on admission, 88 (24%) received it. Among the 321 patients ≥65 years old who had no contraindications to aspirin at hospital discharge, 208 (65%) were prescribed it. When 1995 was compared with 1993 to 1994, the use of aspirin (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.3 to 4.0) and heparin (OR 2.8, 95% CI 1.6 to 4.9) on hospital admission significantly increased, and the use of aspirin at discharge (OR 1.4, 95% CI 0.8 to 2.4) increased. Concomitantly, there was a significant reduction in 30-day readmission (OR 0.52, 95% CI 0.27 to 0.99).Conclusions. Our results indicate an improvement in the care and outcomes of elderly patients with unstable angina, but there remain opportunities for further improvement.

Objectives. We sought to determine the use and association with 30-day mortality of intravenous heparin for the treatment of acute myocardial infarction in elderly patients not treated with a reperfusion strategy and without contraindications to anticoagulation.Background. The benefit of using full-dose intravenous heparin for the treatment of acute myocardial infarction in the elderly is not known.Methods. We conducted a retrospective cohort study using hospital medical records of all Medicare beneficiaries admitted to the hospital with an acute myocardial infarction in Alabama, Connecticut, Iowa and Wisconsin from June 1992 through February 1993.Results. Among the 6,935 patients ≥65 years old who had no absolute chart-documented contraindications to heparin, 3,227 (47%) received early full-dose intravenous heparin therapy. After adjustment for baseline differences in demographic, clinical and treatment factors between patients with and without heparin, the use of heparin (odds ratio 1.02, 95% confidence interval 0.87 to 1.18) was not associated with a significantly better 30-day mortality rate.Conclusions. Although intravenous heparin was commonly used for treatment of acute myocardial infarction in the elderly, it was not associated with an improved 30-day mortality rate. Although the findings of this observational study must be interpreted with care, they lead us to question whether the prevalent use of intravenous heparin has therapeutic effectiveness in this population.