Joint Letter to EPA Regarding the Affordable Clean Energy Proposed Rule

Joint Letter to EPA Opposing Repeal of the Clean Power Plan

Calibration of the Pooled Cohort Equations for Atherosclerotic Cardiovascular Disease: An Update: Annals of Internal Medicine: Vol 165, No 11

The latest guidelines from the American College of Cardiology and American Heart Association, released in fall 2013, provide a long-anticipated update to the recommendations of the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). The guidelines incorporate a new risk score for atherosclerotic cardiovascular disease that includes stroke as well as coronary heart disease. After publication, the new pooled cohort equations (PCEs) were evaluated in 15 studies from the United States and Europe, most of which used cohorts that were more contemporary than those used in developing the guidelines. In almost all of these external validation cohorts, the PCEs overestimated the observed risk. This narrative review provides an update of the published reports, an overview of the strengths and weaknesses of these validation efforts, and a discussion of possible reasons for the discrepancies. These issues may be useful in a recalibration process designed to better match predicted and observed risks relevant for current clinical practice.

Should Patients Have Periodic Health Examinations?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center: Annals of Internal Medicine: Vol 164, No 3

Physicians and patients have come to expect that periodic health examinations (PHEs) are a standard part of comprehensive ongoing medical care. However, considerable research has not demonstrated a substantial benefit of the PHE. Given this lack of benefit and the high total cost of PHE to the health care system, the American Board of Internal Medicine (ABIM) Foundation and the Society of General Internal Medicine (SGIM) have identified “routine health checks in asymptomatic patients” as something of low value that physicians and patients should question, as a part of the Choosing Wisely campaign. Two discussants review the debate about PHE and consider the value of PHE for a healthy 70-year-old woman who appreciates seeing her physician annually.

The Effect of Fluvoxamine and Metformin for Fatigue in Patients With Long COVID: An Adaptive Randomized Trial: Annals of Internal Medicine: Vol 179, No 5

Background: Postacute sequelae of SARS-CoV-2, or long COVID, presents a major therapeutic challenge, with fatigue being a prevalent and debilitating symptom. Objective: To assess the efficacy of fluvoxamine and metformin for long COVID fatigue. Design: Randomized, placebo-controlled, adaptive trial. (ClinicalTrials.gov: NCT06128967) Setting: Outpatient sites in Brazil. Participants: 399 adults with fatigue persisting 90 or more days after confirmed SARS-CoV-2 infection. Intervention: Participants were randomly assigned to fluvoxamine (100 mg twice daily), metformin (750 mg twice daily), or matching placebo for 60 days. Measurements: The primary outcome was change in Fatigue Severity Scale (FSS) score. Results: Fluvoxamine showed a significant reduction in fatigue compared with placebo at day 60 (mean difference, −0.43 [95% credible interval {CrI}, −0.80 to −0.07]), with a sustained effect at day 90 (mean difference, −0.58 [CrI, −0.98 to −0.16]). Fluvoxamine also improved quality-of-life scores with high posterior probability. Metformin showed no significant benefit. Adverse events were less frequent with fluvoxamine (20.0%) than with metformin (28.8%) or placebo (29.7%). Grade 3 and higher adverse events were rare across all groups. Limitations: The 90-day follow-up period limits conclusions about the durability of treatment effects, and the exclusive focus on fatigue as the primary outcome does not address other prevalent long COVID symptoms, leaving fluvoxamine's broader therapeutic utility uncertain. Conclusion: Fluvoxamine, but not metformin, may be an effective treatment for reducing fatigue and improving quality of life in patients with long COVID. Primary Funding Source: The Latona Foundation.

Palliative Care Educational App for Family Caregivers of Homebound Patients With Incurable Cancer: A Single-Center Randomized Trial: Annals of Internal Medicine: Vol 178, No 12

Background: Home-based palliative care relies on empowered family caregivers to overcome the limited availability of palliative care professional resources in managing incurable cancer. Objective: To explore whether adding a palliative care educational app to clinical palliative care could enhance health-related quality of life (HRQoL) in homebound patients with incurable cancer. Design: Single-center, open-label, individual randomized trial. (Chinese Clinical Trial Registry: ChiCTR2300077346) Setting: Single site in Shanghai, China. Participants: Patients with incurable cancer (aged ≥18 years; Karnofsky Performance Status ≤70) receiving palliative care along with consistent family caregivers (aged ≥18 years) enrolled between 28 July and 3 November 2023. Intervention: Patient–caregiver pairs were randomly assigned in a 1:1 ratio to either the intervention group (the app plus palliative care as usual [app]) or the control group (palliative care as usual). The app provided multimedia education on symptom and adverse effect management and nursing information for family caregivers. Measurements: The primary outcome was the mean between-group difference at month 2 in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) score, with the summary score ranging from 0 to 100 and higher scores indicating better outcomes. The primary analysis used the intention-to-treat approach. Results: Of 154 randomly assigned pairs, 147 completed baseline assessments (intervention: n = 74; control: n = 73). The mean age of patients was 59.9 years, and 42.9% were female. At month 2, EORTC QLQ-C30 summary scores were 51.9 (95% CI, 45.4 to 58.5) in the intervention group and 35.7 (CI, 28.6 to 42.9) in the control group, with a mean difference of 16.2 (CI, 9.3 to 23.1). Limitations: Single-center design in China, Chinese-only WeChat app platform, unknown education levels of caregivers and patients, open-label design, and short 2-month follow-up with self-reported outcomes. Conclusion: The palliative care educational app through WeChat improved HRQoL among patients with incurable cancer at 2 months. This finding has implications for future study and development. Primary Funding Source: Shanghai Xingchuan Health Technology Co., Ltd.

Effects of a Hospital-Based Violence Intervention Program on Community Violence in Boston, Massachusetts: A Target Trial Emulation: Annals of Internal Medicine: Vol 179, No 3

Background: Hospital-based violence intervention programs (HVIPs) are widespread, but their effectiveness for violence prevention is unclear. Objective: To determine the effects of Boston Medical Center’s HVIP on future violence outcomes among violently injured young adults. Design: Target trial emulation using observational data. Setting: Boston, Massachusetts. Participants: Young adults aged 16 to 34 years who survived a shooting or stabbing. Intervention: Target trials of 2 treatment strategies using the same eligibility criteria, time zero, and control group were emulated: 1) any treatment: engaging with the HVIP within 1 month of injury and 2) sustained treatment: initiating within 1 month and engaging more than 4 of the first 8 weeks. Measurements: Combined measure of violent reinjury or violence perpetration at 1, 2, and 3 years, using hospital and police data. Results: 1328 patients met criteria; 565 (42.5%) initiated within 1 month. Of these, 58 (10.2%) sustained engagement. In the any-treatment analysis, estimated cumulative incidence was roughly equal between the treatment and control strategies at 1, 2, and 3 years. In the sustained engagement analysis, treatment was associated with considerably lower cumulative incidence (4.5% [95% CI, 1.1% to 9.3%] at 1 year; 5.1% [CI, 1.1% to 9.3%] at 2 years; 6.4% [CI, 1.4% to 12.9%] at 3 years) versus the control strategy (8.7% [CI, 6.6% to 10.0%] at 1 year; 12.3% [CI, 10.2% to 14.5%] at 2 years; 14.3% [CI, 11.8% to 16.6%] at 3 years), with corresponding risk reductions of 47.6% (CI, −19.8% to 86.7%), 58.5% (CI, 21.6% to 91.2%), and 55.3% (CI, 4.9% to 90.2%). Confidence intervals were wide. Limitation: Despite our target trial emulation approach, results could be confounded by unmeasured factors associated with program engagement. Conclusion: Although HVIPs can improve long-term violence outcomes, these effects seem to require intensive participant engagement. Primary Funding Source: Fund for a Safer Future.

Engineering Infection Controls to Reduce Indoor Transmission of Respiratory Infections: A Scoping Review: Annals of Internal Medicine: Vol 178, No 9

Background: Engineering infection controls include a wide range of interventions used indoors to reduce occupants’ exposure to respiratory pathogens. Purpose: To identify and describe primary studies evaluating the effects of engineering infection control interventions designed to reduce the spread of respiratory infections transmitted through indoor air. Data Sources: MEDLINE, Embase, Global Health, Cochrane Central Register of Controlled Trials, CINAHL, Scopus, and Environmental Science Collection from database inception to 12 December 2023. Study Selection: English-language primary research articles evaluating engineering infection control interventions. Data Extraction: Publication information, population characteristics, intervention details, and all relevant outcomes were abstracted by a reviewer and verified by a second, senior reviewer. Data Synthesis: A total of 672 studies published between 1929 and 2024 were identified. Most (n = 606) evaluated environmental samples only, 57 included human participants, and 9 included sentinel animal subjects. About half of the studies included at least 1 intervention classified as pathogen inactivation (n = 405), with fewer involving pathogen removal (n = 200) or air exchange or dilution (n = 143). Across all studies, about half (n = 332) measured the quantity of viable nonpathogenic organisms from air samples, followed by the quantity of nonbiological particulates (n = 197) or viable pathogenic organisms (n = 149). Harms, such as toxic byproducts, were rarely measured. Limitation: Exclusion of non–English-language publications and gray literature. Conclusion: There is substantial heterogeneity in the available evidence. Gaps in evidence include studies measuring efficacy outcomes that are highly relevant for human infection transmission or harms. Refinements in classification of interventions and outcomes could strengthen reporting of these evaluations. Primary Funding Source: National Institute for Occupational Safety and Health at the Centers for Disease Control and Prevention. (Registered on Open Science Framework [https://osf.io/5zmhd]).

The Effect of 4:3 Intermittent Fasting on Weight Loss at 12 Months: A Randomized Clinical Trial: Annals of Internal Medicine: Vol 178, No 5

Background: Long-term (≥12 months) randomized trials evaluating the efficacy of intermittent fasting (IMF) as a dietary weight loss strategy are limited. Furthermore, no studies have compared IMF versus daily caloric restriction (DCR) when both interventions are provided in the context of a guidelines-based behavioral weight loss program. Objective: To compare the effects of 4:3 IMF versus DCR on changes in weight at 12 months, with comprehensive behavioral support provided to both groups. Design: Randomized clinical trial. (ClinicalTrials.gov: NCT03411356) Setting: Denver, Colorado, and surrounding metropolitan area. Participants: Adults aged 18 to 60 years with body mass index (BMI) of 27 to 46 kg/m2. Intervention: The IMF group was instructed to restrict energy intake by 80% on 3 nonconsecutive days per week, with ad libitum intake (no restriction) the other 4 days (4:3 IMF). The DCR group was instructed to reduce daily energy intake by 34% to match the weekly energy deficit of 4:3 IMF. Both groups received a high-intensity comprehensive behavioral weight loss program that included group-based behavioral support and a recommendation to increase moderate-intensity physical activity to 300 minutes per week. Measurements: The primary outcome was change in body weight (in kilograms) at 12 months. Results: Of the 165 (4:3 IMF, n = 84; DCR, n = 81) randomly assigned participants (mean age, 42 years [SD, 9]; mean BMI, 34.1 kg/m2 [SD, 4.4]; 73.9% female), 125 completed the trial. In an intention-to-treat analysis, 4:3 IMF showed greater reductions in weight than DCR at 12 months (mean difference, 2.89 kg [95% CI, 5.65 to 0.14 kg]; P = 0.040). Limitation: Limited generalizability. Conclusion: Compared with DCR, 4:3 IMF resulted in modestly greater weight loss among adults with overweight or obesity enrolled in a 12-month, high-intensity, comprehensive behavioral weight loss program. Primary Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases.

Attention Among Health Care Professionals: A Scoping Review: Annals of Internal Medicine: Vol 177, No 7

Background: The concept of attention can provide insight into the needs of clinicians and how health systems design can impact patient care quality and medical errors. Purpose: To conduct a scoping review to 1) identify and characterize literature relevant to clinician attention; 2) compile metrics used to measure attention; and 3) create a framework of key concepts. Data Sources: Cumulated Index to Nursing and Allied Health Literature (CINAHL), Medline (PubMed), and Embase (Ovid) from 2001 to 26 February 2024. Study Selection: English-language studies addressing health care worker attention in patient care. At least dual review and data abstraction. Data Extraction: Article information, health care professional studied, practice environment, study design and intent, factor type related to attention, and metrics of attention used. Data Synthesis: Of 6448 screened articles, 585 met inclusion criteria. Most studies were descriptive (n = 469) versus investigational (n = 116). More studies focused on barriers to attention (n = 387; 342 descriptive and 45 investigational) versus facilitators to improving attention (n = 198; 112 descriptive and 86 investigational). We developed a framework, grouping studies into 6 categories: 1) definitions of attention, 2) the clinical environment and its effect on attention, 3) personal factors affecting attention, 4) relationships between interventions or factors that affect attention and patient outcomes, 5) the effect of clinical alarms and alarm fatigue on attention, and 6) health information technology’s effect on attention. Eighty-two metrics were used to measure attention. Limitations: Does not synthesize answers to specific questions. Quality of studies was not assessed. Conclusion: This overview may be a resource for researchers, quality improvement experts, and health system leaders to improve clinical environments. Future systematic reviews may synthesize evidence on metrics to measure attention and on the effectiveness of barriers or facilitators related to attention. Primary Funding Source: None.

Association of Medicare Advantage Enrollment With Financial Burden of Care: A Retrospective Cohort Study: Annals of Internal Medicine: Vol 177, No 7

Background: Compared with traditional Medicare (TM), Medicare Advantage (MA) plans typically offer supplemental benefits and lower copayments for in-network services and must include an out-of-pocket spending limit. Objective: To examine whether the financial burden of care decreased for persons switching from TM to MA (TM-to-MA switchers) relative to those remaining in TM (TM stayers). Design: Retrospective longitudinal cohort study comparing changes in financial outcomes between TM-to-MA switchers and TM stayers. Setting: Population-based. Participants: 7054 TM stayers and 1544 TM-to-MA switchers from the Medical Expenditure Panel Survey, 2014 to 2021. Measurements: Individual health care costs (out-of-pocket spending and cost sharing), financial burden (high and catastrophic), and subjective financial hardship (difficulty paying medical bills, paying medical bills over time, and inability to pay medical bills). Results: Compared with TM stayers, TM-to-MA switchers had small differences in out-of-pocket spending ($168 [95% CI, −$133 to $469]) and proportions of total health expenses paid out of pocket (cost sharing) (0.2 percentage point [CI, −1.3 to 1.7 percentage points]), families with out-of-pocket spending greater than 20% of their income (high financial burden) (0.3 percentage point [CI, −2.5 to 3.0 percentage points]), families reporting out-of-pocket spending greater than 40% of their income (catastrophic financial burden) (0.7 percentage point [CI, −0.1 to 1.6 percentage points]), families reporting paying medical bills over time (−0.2 percentage point [CI, −1.7 to 1.4 percentage points]), families having problems paying medical bills (−0.4 percentage point [CI, −2.7 to 1.8 percentage points]), and families reporting being unable to pay medical bills (0.4 percentage point [CI, −1.3 to 2.0 percentage points]). Limitation: Inability to account for all medical care and cost needs and variations across MA plans, small baseline differences in out-of-pocket spending, and potential residual confounding. Conclusion: Differences in financial outcomes between beneficiaries who switched from TM to MA and those who stayed with TM were small. Differences in financial burden ranged across outcomes and did not have a consistent pattern. Primary Funding Source: The National Research Foundation of Korea.

How Would You Manage This Patient With Heart Failure With Preserved Ejection Fraction?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center: Annals of Internal Medicine: Vol 176, No 12

The proportion of patients with new-onset heart failure who have preserved rather than reduced left ventricular ejection fraction (HFpEF and HFrEF) has been increasing over recent decades. In fact, HFpEF now outweighs HFrEF as the predominant heart failure subtype and likely remains underdiagnosed in the community. This is due in part to an aging population and a rise in other risk factors for HFpEF, including obesity and associated cardiometabolic disease. Whereas the diagnosis of HFrEF is relatively straightforward, the diagnosis of HFpEF is often more challenging because there can be other causes for symptoms, including dyspnea and fatigue, and cardinal physical examination findings of elevated jugular venous pressure or pulmonary congestion may not be evident at rest. In 2022, the American College of Cardiology, the American Heart Association, and the Heart Failure Society of America published a comprehensive guideline on heart failure that included recommendations for the management of HFpEF. The use of diuretics for the management of congestion remained the only class 1 (strong) recommendation. New recommendations included broader use of sodium–glucose cotransporter-2 inhibitors (SGLT2i, class 2a), and angiotensin receptor–neprilysin inhibitors (class 2b). In 2023, the American College of Cardiology published an expert consensus decision pathway for the management of HFpEF that suggests treatment strategies based on sex assigned at birth, ejection fraction, clinical evidence of congestion, and candidacy for SGLT2i therapy. Here, 2 experts, a cardiologist and a geriatrician, discuss their approach to the diagnosis and management of HFpEF and how they would apply guidelines to an individual patient.