Randomized Clinical Trial of the Year
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2855594

As an Associate Editor of JAMA Internal Medicine, I am excited to highlight the randomized clinical trial by Panay et al, which is my pick for the best clinical trial published in JAMA Internal Medicine last year. This study addressed a health condition that affects millions of women worldwide: menopause. Some women experience mild symptoms, and for others, vasomotor and sleep symptoms can seriously disrupt functioning and quality of life. Not all women are able to use hormone therapies. However, the widespread use of non–evidence-based menopause symptom management (eg, black cohosh, primrose oil, vitamin E, and phytoestrogens) is concerning due to the lack of efficacy or safety data.

Emergency Department Hepatitis C Virus Testing
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2855593

The emergency department (ED) is a primary health care touchpoint for many individuals with undiagnosed hepatitis C virus (HCV), particularly those with risk factors for HCV, including injection drug use and recent incarceration. In addition to providing lifesaving treatments for acute illnesses and injuries, the ED has emerged as an important setting for identifying untreated chronic diseases, particularly for patients without a usual source of preventive care. Thus, the ED provides a critical opportunity to identify patients with untreated HCV and to provide linkage to care. By testing for HCV and facilitating treatment, EDs have the capacity to improve both individual and community health by expanding access to care among populations who may have otherwise remained underserved.

Rethinking the REMS Program
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2855592

The Risk Evaluation and Mitigation Strategies (REMS) program was formally established under the Food and Drug Administration Amendments Act of 2007 to provide the US Food and Drug Administration (FDA) with additional tools to mitigate medication risks and ensure that benefits outweigh risks. Strategies are individualized to each drug and designed to address a specific safety concern identified by the agency. These can include communication of information to patients or clinicians or specific requirements as part of the prescription or dispensing process. As part of the REMS program, manufacturers are required to submit assessment reports to the FDA at 18 months, 3 years, and 7 years after approval at minimum, which the agency reviews before determining if the REMS should be modified and if the REMS has been successful in meeting its mitigation goal.

Therapy for Adults With Complicated Urinary Tract Infection
https://jamanetwork.com/journals/jama/fullarticle/2855490

This Clinical Guidelines Synopsis summarizes the 2025 Infectious Diseases Society of America guidelines on treatment and management of complicated urinary tract infections in adults.

Vascular Risk Factors and Late-Onset Epilepsy
https://jamanetwork.com/journals/jamaneurology/fullarticle/2855276

This pooled analysis of 6 US cohorts identifies vascular risk factors associated with incident late-onset epilepsy in older adults.

The Patient I Could Not Save
https://jamanetwork.com/journals/jamaneurology/fullarticle/2855275

This essay describes the author’s experience with severe postpartum anxiety and depression, suicidal ideation, and her time on an inpatient psychiatry unit.

E-Cigarettes—Lessons From History and Implications for Public Health
https://jamanetwork.com/journals/jamacardiology/fullarticle/2855456

The compelling evidence of the adverse consequences of e-cigarette use continues to accumulate. We now recognize that the inhalation of a heated nicotine-containing vapor leads to the appearance of pathological changes in respiratory and vascular function—changes known to portend the development of cardiovascular and respiratory disease. In this issue of JAMA Cardiology, Boidin and colleagues describe findings that contribute to the burgeoning body of evidence attesting to the pathophysiological consequences of vaping (the use of e-cigarettes). E-cigarettes deliver levels of nicotine much higher than can be produced by conventional combusted-tobacco products. Their use is facilitated and perpetuated by a countless array of flavors with specific appeal to youth, deft social marketing, and, most importantly, by the rapid development of nicotine addiction—typically within a few days of regular use—a rapidity generally unappreciated by many clinicians. Nicotine has very specific deleterious impacts on the developing adolescent brain and has been described as being the gateway drug facilitating subsequent drug dependencies—underscoring the importance of protecting a vulnerable youth population. Electronic cigarettes and other alternative nicotine-delivery devices are the products of a tobacco industry that aims to promote nicotine addiction.

Childhood Cancer Risk After Assisted Reproductive Technology
https://jamanetwork.com/journals/jama/fullarticle/2855689

This extended follow-up of a cohort study reassesses associations between use of assisted reproductive technology (ART) and childhood cancer overall and by ART modality and cancer type.

Obesity in Children Aged 2 to 12 Years
https://jamanetwork.com/journals/jama/fullarticle/2855679

This narrative review examines obesity in children aged 2 to 12 years, including its epidemiology, pathophysiology, diagnosis, and treatment, such as intensive health behavior and lifestyle treatment and approved pharmacotherapies.

Reassessing Lumbar Punctures for Very Young Febrile Infants
https://jamanetwork.com/journals/jama/fullarticle/2855678

This Viewpoint examines the use of lumbar puncture in febrile young infants and how recent evidence and tools, such as novel blood biomarkers, have shaped understanding of the procedure.

Metabolic Dysfunction–Associated Steatotic Liver Disease in Children and Adolescents
https://jamanetwork.com/journals/jama/fullarticle/2855687

This JAMA Insights discusses the diagnosis, treatment, and prognosis of metabolic dysfunction–associated steatotic liver disease in children and adolescents.

National and County-Level Trends in Opioid Dispensing
https://jamanetwork.com/journals/jama/fullarticle/2855686

This cross-sectional study uses US pharmacy data to examine national and county-level opioid dispensing patterns from 2019 through 2025.

Nonfatal Drug Overdoses and Naloxone Use
https://jamanetwork.com/journals/jama/fullarticle/2855685

This study uses national emergency medical service (EMS) data to examine temporal changes in nonfatal overdoses and naloxone administrations by EMS clinicians and laypersons relative to the US national peak in overdose deaths.

Prone Positioning for Infants With Bronchiolitis and HFNC Support—Reply
https://jamanetwork.com/journals/jama/fullarticle/2855683

In Reply We thank Drs van Egmond and Mulier for their letter about the PROPOSITIS study. They raise an important point regarding the need to report the prone positioning procedure and the effects of prone positioning beyond transpulmonary pressure gradients.

Obesity and Starvation
https://jamanetwork.com/journals/jama/fullarticle/2855725

The essence of the successful method for reducing weight … lies in keeping the intake of energy below that of the output. Theoretically, complete fasting constitutes the most prompt method of accomplishing the end sought. It is a well-recognized fact, however, that starvation prolonged over a period of more than a few days, either voluntarily or as an incident of disease, may lead to unpleasant symptoms. Headache, nausea and dizziness portend the existence of conditions that are not exactly normal, and frequently they can be made to disappear promptly by the ingestion of even a little food. Most modern “treatments” for obesity, therefore, consist in underfeeding rather than complete fasting, particular care being directed to conserving the protein of the body so that the reduction in weight shall represent essentially a loss of body fat oxidized to furnish energy to the underfed individual.

Risk of Inflammatory Bowel Disease After Anti-CD20 Treatment in MS
https://jamanetwork.com/journals/jamaneurology/fullarticle/2855706

This cohort study investigates if anti-CD20 treatment is associated with an increase in the risk of inflammatory bowel disease in individuals with multiple sclerosis (MS).

Rituximab Maintenance in Eosinophilic Granulomatosis With Polyangiitis
https://jamanetwork.com/journals/jama/fullarticle/2855726

Eosinophilic granulomatosis with polyangiitis (EGPA) is the rarest of the antineutrophil cytoplasmic antibody (ANCA)–associated vasculitides and is defined clinically by asthma, eosinophilia, chronic rhinosinusitis, pulmonary infiltrates, and necrotizing vasculitis and eosinophil-rich granulomatous inflammation involving a variety of organ systems. Only 30% to 40% of patients are ANCA positive (usually against myeloperoxidase), and ANCA status often correlates with distinct but overlapping clinical patterns. Historically, glucocorticoids have been the mainstay of EGPA treatment; although the treatment has never been tested adequately prospectively, patients with organ- or life-threatening disease typically receive remission induction with high-dose glucocorticoids plus cyclophosphamide or, in select cases, rituximab. Patients without organ-threatening manifestations have been treated with glucocorticoids alone or in combination with steroid-sparing agents such as azathioprine, methotrexate, or mycophenolate. Maintenance strategies with conventional immunosuppressants are supported largely by observational data, and none have been shown to prolong relapse-free survival compared with glucocorticoid monotherapy. Moreover, major challenges remain: glucocorticoid toxicity is substantial, asthma and sinonasal disease often persist despite vasculitis control, and distinguishing vasculitis relapse from respiratory exacerbations remains difficult.

Reforming Risk Adjustment in Medicare Advantage
https://jamanetwork.com/journals/jama/fullarticle/2855716

This Viewpoint outlines reforms to Medicare Advantage risk adjustment to help limit overspending, including extending the reference period used to calculate Medicare risk scores and excluding diagnoses solely from in-home assessments.

Rituximab vs Azathioprine for Eosinophilic Granulomatosis With Polyangiitis Maintenance Therapy Research Summary
https://jamanetwork.com/journals/jama/fullarticle/2855717

This trial compared rituximab with azathioprine for maintaining remission after recent remission of eosinophilic granulomatosis with polyangiitis vasculitis.

Compounded GLP-1 Dispensing Patterns and Vitamin B 12 Coformulation
https://jamanetwork.com/journals/jama/fullarticle/2855724

This study uses comprehensive prescription drug monitoring program data to describe compounded weight-loss prescriptions, rates of self-payment, out-of-state dispensing, and the ingredients contained in compounded GLP-1s.