Medetomidine Exposure in a Shifting Drug Landscape: Insights From Patient Experiences

Exercise Therapy and Education for Young Adults With Persistent Knee Problems After Anterior Cruciate Ligament Reconstruction: A Randomized Clinical Trial: Annals of Internal Medicine: Vol 0, No 0

Background: Chronic knee symptoms and early-onset osteoarthritis are common after anterior cruciate ligament reconstruction (ACLR). Evidence to inform management is needed. Objective: To evaluate whether physiotherapist-supervised exercise therapy with education is superior to a single education session and self-directed exercise resource for young adults with persistent knee problems after ACLR. Design: Parallel-group randomized trial. (Australian New Zealand Clinical Trials Registry: ACTRN12620001164987). Setting: Community. Participants: 184 young adults (aged 18 to 40 years) with persistent knee problems 9 to 36 months after ACLR. Intervention: A 4-month twice-weekly physiotherapist-supervised exercise therapy program with education (SUPER [SUpervised exercise-therapy and Patient Education Rehabilitation]; n = 92) and a single physiotherapist-delivered education session and self-directed exercise resource (control; n = 92). Measurements: Primary outcome was 4-month change in the composite Knee injury and Osteoarthritis Outcome Score (KOOS4; 0 = worst, 100 = best). Secondary outcomes included KOOS4 at 12 months and thigh muscle strength, patient-perceived global rating of change, and cartilage thickness and composition on magnetic resonance imaging at 4 and 12 months. Results: 184 participants were randomly assigned (mean age, 30 years [SD, 6]; 2.2 years [SD, 0.7] after ACLR); 178 (97%) and 174 (95%) completed 4-month and 12-month follow-up, respectively. At 4 months, KOOS4 scores improved more in the SUPER group than in the control group (14.1 vs. 9.4; adjusted mean difference, 4.8 [95% CI, 1.4 to 8.2]). At 4 months, SUPER resulted in greater muscle strength gains and higher rates of success on global rating of change (for example, pain 73% vs. 40%). Between-group differences narrowed at 12 months as the control group continued to improve, whereas SUPER gains were sustained. There were no between-group differences seen in cartilage thickness or composition. Limitation: Unblinded participants. Conclusion: For young adults with persistent knee problems after ACLR, physiotherapist-supervised exercise therapy with education improved patient-reported outcomes compared with a single education session and self-directed exercise resource, but these between-group differences may not be sustained over time. Primary Funding Source: National Health and Medical Research Council.

Sleep medicine for seniors

Summary for Patients: Fluvoxamine and Metformin for Fatigue in Patients With Long COVID

Effect of Fluvoxamine and Metformin for Fatigue in Patients With Long COVID: An Adaptive Randomized Trial: Annals of Internal Medicine: Vol 0, No 0

Background: Postacute sequelae of SARS-CoV-2 infection (long COVID) presents a therapeutic challenge, with fatigue being a common, debilitating symptom. Objective: To assess the efficacy of fluvoxamine and metformin to treat long COVID fatigue. Design: Randomized, placebo-controlled, adaptive trial. (ClinicalTrials.gov: NCT06128967) Setting: Outpatient sites in Brazil. Participants: 399 adults with fatigue 90 days to 24 months after confirmed SARS-CoV-2 infection. Intervention: Participants were randomly assigned to fluvoxamine (100 mg twice daily [BID]), extended-release metformin (750 mg BID [n = 71] from October 2023 to April 2024; reduced to 500 mg BID [n = 40] in May 2024 after a protocol amendment until the group was stopped for futility in September 2024), or a matching placebo, each for 60 days with follow-up to day 90. Measurements: Change in Fatigue Severity Scale (FSS) score. Results: Median baseline FSS scores ranged from 5.6 to 5.9 across all study groups. The treatment effect on FSS score for fluvoxamine versus placebo showed a mean difference of −0.43 at day 60 and −0.58 at day 90; both had a posterior probability of superiority of 99%. Fluvoxamine also improved quality-of-life scores with a high posterior probability of superiority. Findings for metformin were inconclusive. Incidence of adverse events was lower for fluvoxamine (24.0%) than for metformin, 750 mg BID (45.1%); metformin, 500 mg BID (42.5%); and placebo (35.5%). Grade 3 or higher adverse events were rare (≤2.7%), with no treatment-related deaths. Limitations: The results were inconclusive for metformin because of a dose change recommended by the data safety and monitoring committee due to adverse effects causing study withdrawal and early termination. The benefit of fluvoxamine after 90 days is unknown. The trial did not address other long COVID symptoms. Conclusion: Fluvoxamine shows potential for improving long COVID–associated fatigue and quality of life. Primary Funding Source: The Latona Foundation.

Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is a common but frequently undiagnosed condition. Symptoms include loud snoring, nocturnal awakening, and daytime sleepiness. Treating OSA can meaningfully improve symptoms and achieve modest reductions in blood pressure. Although OSA care has traditionally been limited to sleep specialists, technologies are available that allow primary care clinicians to diagnose OSA and initiate treatment. Treatments include positional therapy, weight management, application of external positive airway pressure, mandibular advancement devices, and surgical interventions. Inpatient identification and management of OSA is also feasible and is an evolving area of research and practice.

Pragmatic Trials: The Importance of Foundational Research, Fidelity, Implementation, and Context

Thyroid Function Reference Intervals by Age, Sex, and Race

Tobacco Use Treatment: Synopsis of the 2026 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline

Description: A work group representing the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) prepared a new VA/DoD clinical practice guideline (CPG) for tobacco use treatment. This article provides a synopsis of the 2026 CPG, which addresses use of commercially available tobacco and nicotine products. Methods: A multidisciplinary work group developed 19 key questions on clinical topics of highest priority for the VA and DoD populations. Published literature from 1 January 2014 to 10 December 2024 was systematically reviewed using the PICOTS (population, intervention, comparator, outcomes, timing of outcomes measurement, and setting) framework. Recommendations were made by consensus and informed by evaluation using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method, which assesses quality of evidence and balances benefits and harms, patient preferences, and feasibility. The final document incorporated input from peer review by an external group of experts. Recommendations: The 2026 guideline includes 32 recommendations across 10 topic areas. Key recommendations for increasing abstinence from combustible tobacco include recommending motivational interviewing to increase engagement in treatment of tobacco and nicotine use (strong) and use of U.S. Food and Drug Administration–approved pharmacotherapies (strong), with varenicline recommended over monotherapy with other agents (strong), combination nicotine replacement therapy ([NRT] for example, patch plus lozenge) recommended over NRT monotherapy (single agent) (strong), and extending use of bupropion sustained release beyond 12 weeks (weak). Other key recommendations include varenicline for increasing abstinence from smokeless tobacco (strong) and electronic nicotine delivery systems (weak) and use of NRT or varenicline to increase quit attempts and abstinence in patients not ready to quit in the next 30 days (weak).

How Would You Manage This Patient With Iron Deficiency Anemia? Grand Rounds Discussion From Beth Israel Deaconess Medical Center

Iron deficiency anemia (IDA) is the most common cause of anemia worldwide and a major cause of disability, manifesting with symptoms including fatigue, weakness, exercise intolerance, worsening heart failure, impaired concentration, irritability, and depression. Women of reproductive age are disproportionately affected due to menstrual blood loss and gynecologic disorders. Iron deficiency anemia is diagnosed in patients who have both iron deficiency (ID), noted by low ferritin level and/or transferrin saturation, and anemia. Notably, iron deficiency (ID) can also occur in the absence of anemia, and overreliance on hemoglobin thresholds may risk missing the diagnosis in menstruating women due to flawed sex-specific reference ranges. Work-up for ID and IDA should focus on identifying the underlying cause of anemia, and may include a gynecologic work-up, bidirectional endoscopy, testing for Helicobacter pylori infection and celiac disease, as well as administering a trial of iron. Iron deficiency can be treated with either oral or intravenous iron. Although several guidelines address the diagnosis or management of ID and IDA, they differ in their recommendations based on the population studied, the clinical context, and the quality of the underlying evidence. Here, 2 hematologists and coauthors of the 2025 Iron Consortium Guideline published in Lancet Haematology discuss areas of guideline uncertainty relating to the diagnosis, evaluation, and treatment of patients with IDA and for Ms. B, a young woman diagnosed with ID.