Mid- and Long-Term Health Risks in Living Kidney Donors: A Systematic Review and Meta-analysis: Annals of Internal Medicine: Vol 168, No 4

Background: Long-term health risks for adults who donate kidneys are unclear. Purpose: To summarize evidence about mid- and long-term health risks associated with living kidney donation in adults. Data Sources: PubMed, Embase, Scopus, and PsycINFO without language restriction from April 1964 to July 2017. Study Selection: Observational studies with at least 1 year of follow-up that compared health outcomes in adult living kidney donors versus nondonor populations. Data Extraction: Two investigators independently extracted study data and assessed study quality. Data Synthesis: 52 studies, comprising 118 426 living kidney donors and 117 656 nondonors, were included. Average follow-up was 1 to 24 years. No evidence suggested higher risk for all-cause mortality, cardiovascular disease, hypertension, type 2 diabetes, or adverse psychosocial health outcomes in living kidney donors than in nondonor populations. Donors had higher diastolic blood pressure, lower estimated glomerular filtration rates, and higher risk for end-stage renal disease (ESRD) (relative risk [RR], 8.83 [95% CI, 1.02 to 20.93]) and preeclampsia in female donors (RR, 2.12 [CI, 1.06 to 4.27]). Despite the increased RR, donors had low absolute risk for ESRD (incidence rate, 0.5 event [CI, 0.1 to 4.9 events] per 1000 person-years) and preeclampsia (incidence rate, 5.9 events [CI, 2.9 to 8.9 events] per 100 pregnancies). Limitation: Generalizability was limited by selected control populations, few studies reported pregnancy-related outcomes, and few studies were from low- and middle-income countries. Conclusion: Although living kidney donation is associated with higher RRs for ESRD and preeclampsia, the absolute risk for these outcomes remains low. Compared with nondonor populations, living kidney donors have no increased risk for other major chronic diseases, such as type 2 diabetes, or for adverse psychosocial outcomes. Primary Funding Source: National Health Service Blood and Transplant and National Institute for Health Research. (PROSPERO: CRD42017072284)

Diagnostic Reasoning: An Endangered Competency in Internal Medicine Training

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.

Infection Surveillance at 50: Are We Still Measuring What Matters?

Expanding Technology-Enabled, Nurse-Delivered Chronic Disease Care: A Pragmatic, Randomized, Effectiveness–Implementation Trial: Annals of Internal Medicine: Vol 179, No 7

Background: Comprehensive telehealth is used effectively for treatment-resistant chronic diseases in certain integrated health systems but has seldom been implemented in systems that provide mainly fee-for-service (FFS) care. Objective: To examine the effectiveness and implementation of comprehensive telehealth delivered in an FFS environment for patients with uncontrolled type 2 diabetes (T2D) and comorbid hypertension. Design: Pragmatic, randomized, effectiveness–implementation trial. (ClinicalTrials.gov: NCT05120544) Setting: 6 academic primary care or endocrinology clinics. Participants: Participants had both T2D with hemoglobin A1c (HbA1c) persistently at 8.0% or higher for at least 6 months and hypertension with at least 1 systolic blood pressure (BP) above 140 mm Hg or diastolic BP above 90 mm Hg in the past year. Intervention: Two 12-month, mobile monitoring–enabled interventions: a self-monitoring control program and a nurse-delivered, comprehensive telehealth program incorporating self-management support and medication management. Measurements: Primary (HbA1c) and secondary outcomes were evaluated at 12 months. Implementation analyses evaluated fidelity and barriers to intervention delivery. Results: Participants were 64% female and 68% Black. The mean age was 54.5 years, mean HbA1c 9.8%, and mean BP 135/81 mm Hg. The estimated mean change in HbA1c from 0 to 12 months was −0.7 percentage points with self-monitoring and −1.1 percentage points with comprehensive telehealth; the estimated mean between-group difference in HbA1c change at 12 months was −0.4 percentage points (95% CI, −1.0 to 0.3 percentage points). Between-group differences in change in secondary outcomes did not reach statistical significance, except for diabetes self-care (0.4 [CI, 0.0 to 0.9], favoring comprehensive telehealth). The comprehensive program was delivered with suboptimal fidelity (median encounters per participant, 9; fidelity threshold, ≥12); analyses identified barriers to program delivery. Limitation: Generalizability to dissimilar populations and systems lacking telehealth infrastructure may be limited. Conclusion: Comprehensive telehealth did not substantially lower HbA1c relative to control in this study. Population factors, intervention and control program design, and barriers to FFS implementation of comprehensive telehealth may have contributed to these findings. Primary Funding Source: National Institute of Nursing Research and Duke Clinical & Translational Science Institute.

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]).