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•Longitudinal systemic bevacizumab is a cost-saving therapeutic option in the care of patients with HHT with moderate-to-severe bleeding.•Cost savings are mediated by decreased need for iron and red blood cell supplementation, hemostatic procedures, and hospitalizations.

IMPORTANCE: Aortic stenosis (AS) is a major public health challenge with a growing therapeutic landscape, but current biomarkers do not inform personalized screening and follow-up. A video-based artificial intelligence (AI) biomarker (Digital AS Severity index [DASSi]) can detect severe AS using single-view long-axis echocardiography without Doppler characterization. OBJECTIVE: To deploy DASSi to patients with no AS or with mild or moderate AS at baseline to identify AS development and progression. DESIGN, SETTING, AND PARTICIPANTS: This is a cohort study that examined 2 cohorts of patients without severe AS undergoing echocardiography in the Yale New Haven Health System (YNHHS; 2015-2021) and Cedars-Sinai Medical Center (CSMC; 2018-2019). A novel computational pipeline for the cross-modal translation of DASSi into cardiac magnetic resonance (CMR) imaging was further developed in the UK Biobank. Analyses were performed between August 2023 and February 2024. EXPOSURE: DASSi (range, 0-1) derived from AI applied to echocardiography and CMR videos. MAIN OUTCOMES AND MEASURES: Annualized change in peak aortic valve velocity (AV-Vmax) and late (>6 months) aortic valve replacement (AVR). RESULTS: A total of 12 599 participants were included in the echocardiographic study (YNHHS: n = 8798; median [IQR] age, 71 [60-80] years; 4250 [48.3%] women; median [IQR] follow-up, 4.1 [2.4-5.4] years; and CSMC: n = 3801; median [IQR] age, 67 [54-78] years; 1685 [44.3%] women; median [IQR] follow-up, 3.4 [2.8-3.9] years). Higher baseline DASSi was associated with faster progression in AV-Vmax (per 0.1 DASSi increment: YNHHS, 0.033 m/s per year [95% CI, 0.028-0.038] among 5483 participants; CSMC, 0.082 m/s per year [95% CI, 0.053-0.111] among 1292 participants), with values of 0.2 or greater associated with a 4- to 5-fold higher AVR risk than values less than 0.2 (YNHHS: 715 events; adjusted hazard ratio [HR], 4.97 [95% CI, 2.71-5.82]; CSMC: 56 events; adjusted HR, 4.04 [95% CI, 0.92-17.70]), independent of age, sex, race, ethnicity, ejection fraction, and AV-Vmax. This was reproduced across 45 474 participants (median [IQR] age, 65 [59-71] years; 23 559 [51.8%] women; median [IQR] follow-up, 2.5 [1.6-3.9] years) undergoing CMR imaging in the UK Biobank (for participants with DASSi ≥0.2 vs those with DASSi <.02, adjusted HR, 11.38 [95% CI, 2.56-50.57]). Saliency maps and phenome-wide association studies supported associations with cardiac structure and function and traditional cardiovascular risk factors. CONCLUSIONS AND RELEVANCE: In this cohort study of patients without severe AS undergoing echocardiography or CMR imaging, a new AI-based video biomarker was independently associated with AS development and progression, enabling opportunistic risk stratification across cardiovascular imaging modalities as well as potential application on handheld devices.

IMPORTANCE: Stroke is a leading cause of death and disability in the US. Accurate and updated measures of stroke burden are needed to guide public health policies. OBJECTIVE: To present burden estimates of ischemic and hemorrhagic stroke in the US in 2019 and describe trends from 1990 to 2019 by age, sex, and geographic location. DESIGN, SETTING, AND PARTICIPANTS: An in-depth cross-sectional analysis of the 2019 Global Burden of Disease study was conducted. The setting included the time period of 1990 to 2019 in the US. The study encompassed estimates for various types of strokes, including all strokes, ischemic strokes, intracerebral hemorrhages (ICHs), and subarachnoid hemorrhages (SAHs). The 2019 Global Burden of Disease results were released on October 20, 2020. EXPOSURES: In this study, no particular exposure was specifically targeted. MAIN OUTCOMES AND MEASURES: The primary focus of this analysis centered on both overall and age-standardized estimates, stroke incidence, prevalence, mortality, and DALYs per 100 000 individuals. RESULTS: In 2019, the US recorded 7.09 million prevalent strokes (4.07 million women [57.4%]; 3.02 million men [42.6%]), with 5.87 million being ischemic strokes (82.7%). Prevalence also included 0.66 million ICHs and 0.85 million SAHs. Although the absolute numbers of stroke cases, mortality, and DALYs surged from 1990 to 2019, the age-standardized rates either declined or remained steady. Notably, hemorrhagic strokes manifested a substantial increase, especially in mortality, compared with ischemic strokes (incidence of ischemic stroke increased by 13% [95% uncertainty interval (UI), 14.2%-11.9%]; incidence of ICH increased by 39.8% [95% UI, 38.9%-39.7%]; incidence of SAH increased by 50.9% [95% UI, 49.2%-52.6%]). The downturn in stroke mortality plateaued in the recent decade. There was a discernible heterogeneity in stroke burden trends, with older adults (50-74 years) experiencing a decrease in incidence in coastal areas (decreases up to 3.9% in Vermont), in contrast to an uptick observed in younger demographics (15-49 years) in the South and Midwest US (with increases up to 8.4% in Minnesota). CONCLUSIONS AND RELEVANCE: In this cross-sectional study, the declining age-standardized stroke rates over the past 3 decades suggest progress in managing stroke-related outcomes. However, the increasing absolute burden of stroke, coupled with a notable rise in hemorrhagic stroke, suggests an evolving and substantial public health challenge in the US. Moreover, the significant disparities in stroke burden trends across different age groups and geographic locations underscore the necessity for region- and demography-specific interventions and policies to effectively mitigate the multifaceted and escalating burden of stroke in the country.

Balancing the safety and efficacy of antithrombotic agents in patients with gastrointestinal disorders is challenging because of the potential for interference with the absorption of antithrombotic drugs and for an increased risk of bleeding. In this Review, we address considerations for enteral antithrombotic therapy in patients with cardiovascular disease and gastrointestinal comorbidities. For those with gastrointestinal bleeding (GIB), we summarize a general scheme for risk stratification and clinical evidence on risk reduction approaches, such as limiting the use of concomitant medications that increase the risk of GIB and the potential utility of gastrointestinal protection strategies (such as proton pump inhibitors or histamine type 2 receptor antagonists). Furthermore, we summarize the best available evidence and potential gaps in our knowledge on tailoring antithrombotic therapy in patients with active or recent GIB and in those at high risk of GIB but without active or recent GIB. Finally, we review the recommendations provided by major medical societies, highlighting the crucial role of teamwork and multidisciplinary discussions to customize the antithrombotic regimen in patients with coexisting cardiovascular and gastrointestinal diseases.

AbstractObjective:To determine change in rates of postoperative pneumonia and ventilator-associated pneumonia among patients hospitalized in the United States during 2009–2019.Design:Retrospective cohort study.Patients:Patients hospitalized for major surgical procedures, acute myocardial infarction, heart failure, and pneumonia.Methods:We conducted a retrospective review of data from the Medicare Patient Safety Monitoring System, a chart-abstraction–derived database including 21 adverse-event measures among patients hospitalized in the United States. Changes in observed and risk-adjusted rates of postoperative pneumonia and ventilator-associated pneumonia were derived.Results:Among 58,618 patients undergoing major surgical procedures between 2009 and 2019, the observed rate of postoperative pneumonia from 2009–2011 was 1.9% and decreased to 1.3% during 2017–2019. The adjusted annual risk each year, compared to the prior year, was 0.94 (95% CI, 0.92–0.96). Among 4,007 patients hospitalized for any of these 4 conditions at risk for ventilator-associated pneumonia during 2009–2019, we did not detect a significant change in observed or adjusted rates. Observed rates clustered around 10%, and adjusted annual risk compared to the prior year was 0.99 (95% CI, 0.95–1.02).Conclusions:During 2009–2019, the rate of postoperative pneumonia decreased statistically and clinically significantly in among patients hospitalized for major surgical procedures in the United States, but rates of ventilator-associated pneumonia among patients hospitalized for major surgical procedures, acute myocardial infarction, heart failure, and pneumonia did not change.

Initiation of evidence-based medications for patients with heart failure with reduced ejection fraction (HFrEF) during hospitalization in contemporary practice is unknown.

The exceptionally rapid development of highly flexible, reusable artificial intelligence (AI) models is likely to usher in newfound capabilities in medicine. We propose a new paradigm for medical AI, which we refer to as generalist medical AI (GMAI). GMAI models will be capable of carrying out a diverse set of tasks using very little or no task-specific labelled data. Built through self-supervision on large, diverse datasets, GMAI will flexibly interpret different combinations of medical modalities, including data from imaging, electronic health records, laboratory results, genomics, graphs or medical text. Models will in turn produce expressive outputs such as free-text explanations, spoken recommendations or image annotations that demonstrate advanced medical reasoning abilities. Here we identify a set of high-impact potential applications for GMAI and lay out specific technical capabilities and training datasets necessary to enable them. We expect that GMAI-enabled applications will challenge current strategies for regulating and validating AI devices for medicine and will shift practices associated with the collection of large medical datasets.

Post-acute infection syndromes may develop after acute viral disease1. Infection with SARS-CoV-2 can result in the development of a post-acute infection syndrome known as long COVID. Individuals with long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions2–4. However, the biological processes that are associated with the development and persistence of these symptoms are unclear. Here 275 individuals with or without long COVID were enrolled in a cross-sectional study that included multidimensional immune phenotyping and unbiased machine learning methods to identify biological features associated with long COVID. Marked differences were noted in circulating myeloid and lymphocyte populations relative to the matched controls, as well as evidence of exaggerated humoral responses directed against SARS-CoV-2 among participants with long COVID. Furthermore, higher antibody responses directed against non-SARS-CoV-2 viral pathogens were observed among individuals with long COVID, particularly Epstein–Barr virus. Levels of soluble immune mediators and hormones varied among groups, with cortisol levels being lower among participants with long COVID. Integration of immune phenotyping data into unbiased machine learning models identified the key features that are most strongly associated with long COVID status. Collectively, these findings may help to guide future studies into the pathobiology of long COVID and help with developing relevant biomarkers.

Objective. To characterize hospitals based on patterns of their combined financial and clinical outcomes for heart failure hospitalizations longitudinally. Data Source. Detailed cost and administrative data on hospitalizations for heart failure from 424 hospitals in the 2005-2011 Premier database. Study Design. Using a mixture modeling approach, we identified groups of hospitals with distinct joint trajectories of risk-standardized cost (RSC) per hospitalization and risk-standardized in-hospital mortality rate (RSMR), and assessed hospital characteristics associated with the distinct patterns using multinomial logistic regression. Principal Findings. During 2005-2011, mean hospital RSC decreased from $12,003 to $10,782, while mean hospital RSMR declined from 3.9 to 3.2 percent. We identified five distinct hospital patterns: highest cost and low mortality (3.2 percent of the hospitals), high cost and low mortality (20.4 percent), medium cost and low mortality (34.6 percent), medium cost and high mortality (6.2 percent), and low cost and low mortality (35.6 percent). Longer hospital stay and greater use of intensive care unit and surgical procedures were associated with phenotypes with higher costs or greater mortality. Conclusions. Hospitals vary substantially in the joint longitudinal patterns of cost and mortality, suggesting marked difference in value of care. Understanding determinants of the variation will inform strategies for improving the value of hospital care. Key Words. Cost, mortality, value of care, trajectory, heart failure, Hospital care is the most expensive component of the national health expenditure in the United States, totaling $814.0 billion in 2010 (Martin et al. 2012). Hospital cost per inpatient stay [...]

IMPORTANCE: The optimal treatment of intermediate-high–risk pulmonary embolism (PE) remains unknown. OBJECTIVE: To assess the effect of conventional catheter-directed thrombolysis (cCDT) plus anticoagulation vs anticoagulation monotherapy in improving echocardiographic measures of right ventricle (RV) to left ventricle (LV) ratio in acute intermediate-high–risk PE. DESIGN, SETTING, AND PARTICIPANTS: The Catheter-Directed Thrombolysis vs Anticoagulation in Patients with Acute Intermediate-High–Risk Pulmonary Embolism (CANARY) trial was an open-label, randomized clinical trial of patients with intermediate-high–risk PE, conducted in 2 large cardiovascular centers in Tehran, Iran, between December 22, 2018, through February 2, 2020. INTERVENTIONS: Patients were randomly assigned to cCDT (alteplase, 0.5 mg/catheter/h for 24 hours) plus heparin vs anticoagulation monotherapy. MAIN OUTCOMES AND MEASURES: The proportion of patients with a 3-month echocardiographic RV/LV ratio greater than 0.9, assessed by a core laboratory, was the primary outcome. The proportion of patients with an RV/LV ratio greater than 0.9 at 72 hours after randomization and the 3-month all-cause mortality were among secondary outcomes. Major bleeding (Bleeding Academic Research Consortium type 3 or 5) was the main safety outcome. A clinical events committee, masked to the treatment assignment, adjudicated clinical outcomes. RESULTS: The study was prematurely stopped due to the COVID-19 pandemic after recruiting 94 patients (mean [SD] age, 58.4 [2.5] years; 27 women [29%]), of whom 85 patients completed the 3-month echocardiographic follow-up. Overall, 2 of 46 patients (4.3%) in the cCDT group and 5 of 39 patients (12.8%) in the anticoagulation monotherapy group met the primary outcome (odds ratio [OR], 0.31; 95% CI, 0.06-1.69; P = .24). The median (IQR) 3-month RV/LV ratio was significantly lower with cCDT (0.7 [0.6-0.7]) than with anticoagulation (0.8 [0.7-0.9); P = .01). An RV/LV ratio greater than 0.9 at 72 hours after randomization was observed in fewer patients treated with cCDT (13 of 48 [27.0%]) than anticoagulation (24 of 46 [52.1%]; OR, 0.34; 95% CI, 0.14-0.80; P = .01). Fewer patients assigned to cCDT experienced a 3-month composite of death or RV/LV greater than 0.9 (2 of 48 [4.3%] vs 8 of 46 [17.3%]; OR, 0.20; 95% CI, 0.04-1.03; P = .048). One case of nonfatal major gastrointestinal bleeding occurred in the cCDT group. CONCLUSIONS AND RELEVANCE: This prematurely terminated randomized clinical trial of patients with intermediate-high–risk PE was hypothesis-generating for improvement in some efficacy outcomes and acceptable rate of major bleeding for cCDT compared with anticoagulation monotherapy and provided support for a definitive clinical outcomes trial. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05172115

OBJECTIVE--We examined the association between Hb[A.sub.1c] level and self-reported severe hypoglycemia in patients with type 2 diabetes. RESEARCH DESIGN AND METNODS--Type 2 diabetic patients in a large, integrated healthcare system, [...]

IMPORTANCE: Dose-reduced regimens of direct oral anticoagulants (DOACs) may be used for 2 main purposes: dose-adjusted treatment intended as full-intensity anticoagulation (eg, for stroke prevention in atrial fibrillation [AF] in patients requiring dose reduction) or low-intensity treatment (eg, extended-duration treatment of venous thromboembolism [VTE]). We reviewed randomized clinical trials (RCTs) to understand the scenarios in which dose-adjusted or low-intensity DOACs were tested and reviewed the labeled indications by regulatory authorities, using data from large registries to assess whether the use of dose-reduced DOACs in routine practice aligned with the findings of RCTs. OBSERVATIONS: Among 4191 screened publications, 35 RCTs that used dose-adjusted DOACs were identified for dabigatran, apixaban, rivaroxaban, and edoxaban. Of these 35 RCTs, 29 were related to stroke prevention in AF. Efficacy and safety results for dose-adjusted DOACs in large RCTs of AF were similar to those found for full-dose DOACs. To our knowledge, dabigatran, apixaban, and rivaroxaban have not been studied as dose-adjusted therapy for acute VTE treatment. Low-intensity DOACs were identified in 37 RCTs. Low-intensity DOACs may be used for extended-duration treatment of VTE (apixaban and rivaroxaban), primary prevention in orthopedic surgeries (dabigatran, apixaban, and rivaroxaban), primary prevention in ambulatory high-risk cancer patients (apixaban and rivaroxaban) or (postdischarge) high-risk medical patients (rivaroxaban), in stable atherosclerotic vascular disease, or after a recent revascularization for peripheral artery disease in conjunction with aspirin (rivaroxaban). Minor variations exist between regulatory authorities in different regions regarding criteria for dose adjustment of DOACs. Data from large registries indicated that dose-reduced DOACs were used occasionally with doses or for clinical scenarios different from those studied in RCTs or recommended by regulatory authorities. CONCLUSIONS AND RELEVANCE: Dose adjustment and low-intensity treatment are 2 different forms of dose-reduced DOACs. Dose adjustment is mostly relevant for AF and should be done based on the approved criteria. Dose adjustment of DOACs should not be used for acute VTE treatment in most cases. In contrast, low-intensity DOACs may be used for primary or secondary VTE prevention for studied and approved indications. Attention should be given to routine practice patterns to align the daily clinical practice with existing evidence of safety and efficacy.

Objective. To identify key characteristics of a national quality campaign that participants viewed as effective, to understand mechanisms by which the campaign influenced hospital practices, and to elucidate contextual factors that modified the perceived influence of the campaign on hospital improvements. Data Sources. In-depth interviews, hospital surveys, and Health Quality Alliance data. Study Design. We conducted a qualitative study using in-depth interviews with clinical and administrative staff (N=99) at hospitals reporting strong influence (n = 6) as well as hospitals reporting limited influence (n = 6) of the Door-to-Balloon (D2B) Alliance, a national quality campaign to improve heart attack care. We analyzed these qualitative data as well as changes in hospital use of recommended strategies reported through a hospital survey and changes in treatment times using Health Quality Alliance data. Data Collection Methods. In-depth, open-ended interviews; hospital survey. Principal Findings. Key characteristics of the national quality campaign viewed as enhancing its effectiveness were as follows: credibility of the recommendations, perceived simplicity of the recommendations, alignment with hospitals' strategic goals, practical implementation tools, and breadth of the network of peer hospitals in the D2B Alliance. Perceived mechanisms of the campaign's influence included raising awareness and influencing goals, fostering strategy adoption, and influencing aspects of organizational culture. Modifying contextual factors included perceptions about current performance and internal championship for the recommended changes. Conclusions. The impact of national quality campaigns may depend on both campaign design features and on the internal environment of participating hospitals. Key Words. Quality improvement, campaigns, hospitals, acute myocardial infarction, Amid persistent evidence that many patients do not receive guideline-based care, national quality campaigns have developed to motivate widespread adoption of evidence-based practices to improve quality of care. Recent examples [...]

Background: Several meta-analyses have evaluated the efficacy of percutaneous coronary intervention (PCI) compared with medical therapy, but none has focused on angina relief. Purpose: To summarize the evidence on the degree of angina relief from PCI compared with medical therapy in patients with stable coronary artery disease. Data Sources: The Cochrane Library (1993 to June 2009), EMBASE (1980 to June 2009), and MEDLINE (1950 to June 2009), with no language restrictions. Study Selection: Two independent reviewers screened citations to identify randomized, controlled trials of PCI versus medical therapy in patients with stable coronary artery disease. Data Extraction: Two independent reviewers abstracted data on patient characteristics, study conduct, and outcomes. A random-effects model was used to combine data on freedom from angina and to perform stratified analyses based on duration of follow-up, inclusion of patients with recent myocardial infarction, coronary stent utilization, recruitment period, and utilization of evidence-based medications. Data Synthesis: A total of 14 trials, enrolling 7818 patients, met the inclusion criteria. Although PCI was associated with an overall benefit on angina relief (odds ratio, 1.69 [95% CI, 1.24 to 2.30]), important heterogeneity across trials was observed. The incremental benefit of PCI observed in older trials (odds ratio, 3.38 [CI, 1.89 to 6.04]) was substantially less and possibly absent in recent trials (odds ratio, 1.13 [CI, 0.76 to 1.68]). An inverse relationship between use of evidence-based therapies and the incremental benefit of PCI was observed. Limitations: Information about the long-term use of medication was incomplete in most trials. Few trials used drug-eluting stents. Meta-regression analyses used aggregated study-level data from few trials. Conclusion: Percutaneous coronary intervention was associated with greater freedom from angina compared with medical therapy, but this benefit was largely attenuated in contemporary studies. This observation may be related to greater use of evidence-based medications in contemporary trials. Primary Funding Source: Canadian Institutes of Health Research.

Background: Although treating to lipid targets ('treat to target') is widely recommended for coronary artery disease (CAD) prevention, some have advocated administering fixed doses of statins based on a person's estimated net benefit ('tailored treatment'). Objective: To examine how a tailored treatment approach to statin therapy compares with a treat-to-target approach. Design: Simulated model of population-level effects of treat-to-target and tailored treatment approaches to statin therapy. Data Sources: Statin trials from 1994 to 2009 and nationally representative CAD risk factor data. Target Population: U.S. persons aged 30 to 75 years with no history of myocardial infarction. Time Horizon: Lifetime effects of 5 years of treatment. Perspective: Societal and patient. Intervention: Tailored treatment based on a person's 5-year CAD risk (simvastatin, 40 mg, for 5% to 15% CAD risk and atorvastatin, 40 mg, for CAD risk >15%) versus treat-to-target approaches that escalate statin dose per National Cholesterol Education Program [NCEP] III guidelines (including an intensive approach that advances treatment whenever intensification is optional by NCEP III criteria). Outcome Measures: Quality-adjusted life-years (QALYs). Results of Base-Case Analysis: Compared with the standard NCEP III approach, the intensive NCEP III approach treated 15 million more persons and saved 570 000 more QALYs over 5 years. The tailored strategy treated a similar number of persons, as did the intensive NCEP III approach, but saved 500 000 more QALYs and treated fewer persons with high-dose statins. Results of Sensitivity Analysis: No circumstances were found in which a treat-to-target approach was preferable to tailored treatment. Limitation: Model assumptions were based on available clinical data, which included few persons 75 years or older. Conclusion: A tailored treatment strategy prevents more CAD events while treating fewer persons with high-dose statins than low-density lipoprotein cholesterol-based target approaches. Results were robust, even with assumptions favoring a treat-to-target approach. Primary Funding Source: Department of Veteran Affairs Health Services Research & Development Service's Quality Enhancement Research Initiative.

Background: Little information is available about factors associated with racial differences across a broad spectrum of post-myocardial infarction outcomes, including patients' symptoms and quality of life. Objective: To determine racial differences in mortality, rehospitalization, angina, and quality of life after myocardial infarction and identify the factors associated with these differences. Design: Prospective cohort study. Setting: 10 hospitals in the United States. Patients: 1849 patients who had myocardial infarction, 28% of whom were black. Measurements: Demographic, economic, clinical, psychosocial, and treatment characteristics and outcomes were prospectively collected. Outcomes included time to 2-year all-cause mortality, 1-year rehospitalization, and Seattle Angina Questionnaire--assessed angina and quality of life. Results: Black patients had higher unadjusted mortality (19.9% vs. 9.3%; P < 0.001) and rehospitalization rates (45.4% vs. 40.4%; P: 0.130), more angina (28.0% vs. 17.8%; < 0.001), and worse mean quality of life (80.6 [SD, 22.5] vs. 85.9 [SD, 17.2]; P 0.001). After adjustment for patient characteristics, black patients trended toward greater mortality (hazard ratio, 1.29 [95% CI, 0.92 to 1.81]; P = 0.142), fewer rehospitalizations (hazard ratio, 0.82 [CI, 0.66 to 1.02]; P = 0.071), and higher likelihood of angina at 1 year (odds ratio, 1.41 [CI, 1.03 to 1.94]; P = 0.032) but similar quality of life (mean difference, -0.6 [CI, -3.4 to 2.2]). Adjustment for site of care further attenuated mortality differences (hazard ratio, 1.04 [CI, 0.71 to 1.52]; P = 0.84). Adjustment for treatments had minimal effect on any association. Limitation: Residual confounding and missing data may have introduced bias. Conclusion: Although black patients with myocardial infarction have worse outcomes than white patients, these differences did not persist after adjustment for patient factors and site of care. Further adjustment for treatments received minimally influenced observed differences. Strategies that focus on improving baseline cardiac risk and hospital factors may do more than treatment-focused strategies to attenuate racial differences in myocardial infarction outcomes. Funding: The National Heart, Lung, and Blood Institute Specialized Center of Clinically Oriented Research in Cardiac Dysfunction and Disease, CV Therapeutics, and Cardiovascular Outcomes.

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.

Background: Seeding trials, clinical studies conducted by pharmaceutical companies that are designed to seem as if they answer a scientific question but primarily fulfill marketing objectives, have not been described in detail. Purpose: To describe a known seeding trial, ADVANTAGE (Assessment of Differences between Vioxx and Naproxen To Ascertain Gastrointestinal Tolerability and Effectiveness), through documents of the trial sponsor, Merck & Co. (Whitehouse Station, New Jersey). Data Sources: Merck internal and external correspondence, reports, and presentations elicited to inform legal proceedings of Cona v Merck and Co., Inc., and McDarby v Merck and Co., Inc. The documents were created between 1998 and 2006. Data Extraction: An iterative case-study process of review, discussion, and re-review of documents to identify themes relevant to the design and conduct of ADVANTAGE. To supplement the case-study review, the authors did a systematic review of the literature to identify published manuscripts focused on seeding trials and their conduct. Data Synthesis: Review of the documents revealed 3 key themes: The trial was designed by Merck's marketing division to fulfill a marketing objective; Merck's marketing division handled both the scientific and the marketing data, including collection, analysis, and dissemination; and Merck hid the marketing nature of the trial from participants, physician investigators, and institutional review board members. Although the systematic review of the literature identified 6 articles that focused on the practice of seeding trials, none provided documentary evidence of their existence or conduct. Limitations: The legal documents in these cases provide useful, but limited, information about the practices of the pharmaceutical industry. This description of 1 company's actions is incomplete and may have limited generalizability. Conclusion: Documentary evidence shows that ADVANTAGE is an example of marketing framed as science. The documents indicate that ADVANTAGE was a seeding trial developed by Merck's marketing division to promote prescription of Vioxx (rofecoxib) when it became available on the market in 1999.

EXECUTIVE SUMMARY Despite substantial improvement in recent years in hospital performance in many quality measures for acute myocardial infarction (AMI), national performance lags in a key publicly reported quality indicator [...]

The US Food and Drug Administration should address health misinformation through existing and new regulatory approaches, including modernizing product labeling, investing in infodemic surveillance and addressing the roles of the internet and social media.

Background: Limits on resident work hours are intended to reduce fatigue-related errors, but may raise risk by increasing transfers of responsibility for patients. Objective: To examine changes in outcomes for internal medicine patients after the implementation of work-hour regulations. Design: Retrospective cohort study. Setting: Urban, academic medical center. Patients: 14 260 consecutive patients discharged from the teaching (housestaff) service and 6664 consecutive patients discharged from the nonteaching (hospitalist) service between 1 July 2002 and 30 June 2004. Measurements: Outcomes included intensive care unit utilization, length of stay, discharge disposition, 30-clay readmission rate to the study institution, pharmacist interventions to prevent error, drug-drug interactions and in-hospital death. Results: The teaching service had net improvements in 3 outcomes. Relative to changes experienced by the nonteaching service, the rate of intensive care unit utilization decreased by 2.1% (95% CI, -3.3% to -0.7%; P = 0.002), the rate of discharge to home or rehabilitation facility versus elsewhere improved by 5.3% (CI, 2.6% to 7.6%; P < 0.001), and pharmacist interventions to prevent error were reduced by 1.92 interventions per 100 patient-days (CI, -2.74 to -1.03 interventions per 100 patient-days; P< 0.001). Teaching and nonteaching services had similar changes over time in length of stay, 30-day readmission rate, and adverse drug-drug interactions. In-hospital death was uncommon in both groups, and change over time was similar in the 2 groups. Limitations: The study was a retrospective, nonrandomized design that assessed a limited number of outcomes. Teaching and non-teaching cohorts may not have been affected similarly by secular trends in patient care. Conclusions: After the implementation of work-hour regulations, 3 of 7 outcomes improved for patients in the teaching service relative to those in the nonteaching service. The authors found no evidence of adverse unintended consequences after the institution of work-hour regulations.

Background: Increasing the racial and ethnic diversity of the physician workforce is a national priority. However, insight into the professional experiences of minority physicians is limited. This knowledge is fundamental to developing effective strategies to recruit, retain, and support a diverse physician workforce. Objective: To characterize how physicians of African descent experience race in the workplace. Design: Qualitative study based on in-person and in-depth racially concordant interviews using a standard discussion guide. Setting: The 6 New England states in the United States. Participants: 25 practicing physicians of African descent representing a diverse range of primary practice settings, specialties, and ages. Measurements: Professional experiences of physicians of African descent. Results: 1) Awareness of race permeates the experience of physicians of African descent in the health care workplace; 2) race-related experiences shape interpersonal interactions and define the institutional climate; 3) responses to perceived racism at work vary along a spectrum from minimization to confrontation; 4) the health care workplace is often silent on issues of race; and 5) collective race-related experiences can result in 'racial fatigue,' with personal and professional consequences for physicians. Limitations: The study was restricted to New England and may not reflect the experiences of physicians in other geographic regions. The findings are meant to be hypothesis-generating and require additional follow-up studies. Conclusions: The issue of race remains a pervasive influence in the work lives of physicians of African descent. Without sufficient attention to the specific ways in which race shapes physicians' work experiences, health care organizations are unlikely to create environments that successfully foster and sustain a diverse physician workforce.

Background: Older adults with shorter life expectancies may receive less benefit from colorectal cancer screening than younger, healthier patients. Objective: To determine the degree to which life expectancy after diagnosis of an early-stage cancer varies according to age or coexisting chronic illness. Design: Retrospective cohort study. Setting: Population-based cancer registry with linked administrative claims data. Patients: Patients 67 years of age or older who received a diagnosis of colorectal cancer from 1993 through 1999. Measurements: Chronic conditions were identified by searching Medicare claims. Using a life-table approach, the authors quantified the degree to which life expectancy associated with each cancer stage at diagnosis varied with patient age, sex, and burden of chronic conditions. Results: The final study sample consisted of 35 755 patients. After accounting for cancer stage at diagnosis, the authors found that life expectancy was strongly related to both age and the burden of chronic illness. Among men who received a diagnosis of stage I cancer at 67 years of age, life expectancy decreased from 19.1 years (95% CI, 17.8 to 20.5 years) for patients with no chronic conditions to 12.4 years (CI, 11.4 to 13.5 years) for those with 1 or 2 conditions and 7.6 years (CI, 6.1 to 9.4 years) for those with 3 or more conditions. A similar trend was noted among female counterparts, with life expectancy decreasing from approximately 23 years to 16 years and 7 years for the 3 chronic condition groups, respectively. For men and women 81 years of age with no chronic illnesses, life expectancy after stage I cancer diagnosis was 10.3 years (CI, 9.2 to 11.9 years) and 13.8 years (CI, 12.3 to 15.3 years), respectively. Limitations: Administrative claims may not identify all chronic conditions. Life expectancy estimates at the population level are averages and, therefore, may not accurately predict the life expectancy of individual patients. Conclusions: Coexisting chronic illness is associated with a substantial reduction in life expectancy after diagnosis of early-stage colorectal cancer. Physicians should consider this when deciding whether to screen older persons.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjmed.2006.03.040 Byline: Judith H. Lichtman (a), Amir Fathi (b), Martha J. Radford (c), Zhenqiu Lin (d), Caroline S. Loeser (e), Harlan M. Krumholz (d)(f)(g)(h) Keywords: Acute myocardial infarction; Mortality; Risk factors Abstract: The study's purpose was to determine the prevalence and prognostic importance of acute, severe, noncardiac conditions present at the time of an acute myocardial infarction (AMI). Author Affiliation: (a) Section of Chronic Disease Epidemiology, Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Conn (b) Department of Medicine, Massachusetts General Hospital, Boston, Mass (c) Division of Cardiology, Department of Medicine, New York University Medical Center, New York, NY (d) Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, Conn (e) Department of Medicine, Yale University School of Medicine, New Haven, Conn (f) Section of Health Policy and Administration, Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Conn (g) Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, Conn (h) Robert Wood Johnson Clinical Scholars Program, Yale University School of Medicine, New Haven, Conn. Article History: Revised 20 March 2006 Article Note: (footnote) Dr. Lichtman is supported by grant number 1 K01 DP000085-01 from the Centers for Disease Control and Prevention (CDC). The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of CDC.