Kansagara D, Terry GE, Ayers CK
… +1 more, D'Souza DC
JAMA Intern Med
· 2026 May · PMID 41801216
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IMPORTANCE: Cannabis use is common among those with mental health conditions, and many people report using cannabis to manage mental health symptoms. It is important for clinicians to understand the lack of clear benefit...IMPORTANCE: Cannabis use is common among those with mental health conditions, and many people report using cannabis to manage mental health symptoms. It is important for clinicians to understand the lack of clear benefits of cannabis for mental health conditions and the potential for substantial adverse effects. OBSERVATIONS: Overall, the potential benefits of cannabis for mental health conditions remain poorly studied. There is low-certainty evidence that Δ-9-tetrahydrocannabinol (THC)-predominant cannabis may not improve symptoms of posttraumatic stress disorder, and there is largely insufficient evidence to characterize the effects of long-term THC-predominant cannabis use on anxiety, depression, and attention-deficit/hyperactivity disorder. There is emerging low-certainty evidence that the cannabis constituent cannabidiol alone may reduce anxiety in patients with anxiety disorders. THC-predominant cannabis use holds substantial risk for adverse mental health effects, and counseling patients about these risks is crucial to promote safety. These risks include worsening mania symptoms and function in those with bipolar disorder and an increase in psychotic symptoms in those with psychotic spectrum disorders. Among people with past-year cannabis use, about 3 in 10 have cannabis use disorder (CUD), and about one-half those with CUD have moderate or severe disease with negative social, employment, or other adverse outcomes. Regular use of high THC-content products by adolescents and young adults is associated with several concerning risks, including an increased risk of psychosis (estimates range from about 2-fold to 11-fold increased risk), a higher risk of CUD, and self-harm in those with mood disorders. Cannabis use should be avoided in individuals at elevated risk of harms, including adolescents and young adults, those with bipolar or psychotic disorders, pregnant individuals, and those at risk for substance use disorders. CONCLUSIONS AND RELEVANCE: The current evidence base is not sufficient to support the use of cannabis for the treatment of mental health conditions and demonstrates substantial risks of adverse effects. Clinicians should engage patients with mental health conditions in discussions about cannabis use because use is common, has an influence on mental health symptoms, and is likely an important modifiable risk factor for mental health conditions in some populations.
JAMA Intern Med
· 2026 May · PMID 41801195
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IMPORTANCE: High prescription drug costs are a pressing national concern and contribute to medication nonadherence and poor health outcomes. The Inflation Reduction Act (IRA) introduced sweeping reforms to improve medica...IMPORTANCE: High prescription drug costs are a pressing national concern and contribute to medication nonadherence and poor health outcomes. The Inflation Reduction Act (IRA) introduced sweeping reforms to improve medication affordability, but their potential impact on medication adherence is unknown. OBJECTIVE: To evaluate the association of the IRA's 2024 prescription drug provisions with cost-related medication nonadherence as well as health care-related financial strain. DESIGN, SETTING, AND PARTICIPANTS: This quasi-experimental difference-in-differences analysis used data from the 2021-2024 National Health Interview Survey. Adults aged 62 to 67 years who were enrolled in Medicare Part D (intervention) or private insurance (comparator) were included. Individuals with incomes 135% or less of the federal poverty level, dually enrolled in Medicaid, and who currently used insulin were excluded from the primary analysis because preexisting protections limited their out-of-pocket spending in Medicare. EXPOSURES: The IRA's prescription drug provisions were enacted on January 1, 2024, including (1) elimination of the 5% coinsurance requirement for catastrophic coverage that effectively capped out-of-pocket drug costs to approximately $3300 per year and (2) expansion of full low-income subsidies. MAIN OUTCOMES AND MEASURES: The primary outcome was cost-related medication nonadherence. The secondary outcome was health care-related financial strain. RESULTS: The study population included 1454 Medicare beneficiaries (weighted mean [SD] age, 66.1 [0.8] years; 53.1% female) and 3797 privately insured comparators (weighted mean [SD] age, 63.3 [1.2] years; 50.7% female). Prior to the 2024 IRA reforms, trends in cost-related medication nonadherence were parallel between the 2 groups. Following implementation of the IRA's 2024 provisions, cost-related medication nonadherence declined among Medicare beneficiaries relative to comparators (adjusted difference-in-differences estimate, -4.9 percentage points [pp]; 95% CI, -8.8 to -1.0 pp). Among Medicare beneficiaries with multiple chronic conditions, the decline was more pronounced (adjusted difference-in-differences estimate, -7.8 pp; 95% CI, -12.9 to -2.8 pp). These findings were robust across multiple sensitivity analyses as well as secondary analyses using Medicare beneficiaries with incomes 135% or less of the federal poverty level and dually enrolled in Medicaid as an alternative comparator group. In contrast, there were no meaningful differential changes observed for health care-related financial strain (adjusted difference-in-differences estimate, -2.6 pp; 95% CI, -10.1 to 5.0 pp). CONCLUSIONS AND RELEVANCE: In this difference-in-differences analysis, the IRA's 2024 prescription drug provisions were associated with a reduction in cost-related medication nonadherence among eligible Medicare beneficiaries in their first year. These early improvements may have important implications for chronic disease management and downstream clinical outcomes.
Khazanchi R, Fleishman A, Eneanya ND
… +4 more, Michelson KA, Diao JA, Morse M, Pavlakis M
JAMA Intern Med
· 2026 May · PMID 41801177
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IMPORTANCE: Until 2021, national guidelines upheld race-based equations that assigned higher kidney function estimates to Black patients, delaying subspecialist referral and transplant waitlisting. In 2023, the Organ Pro...IMPORTANCE: Until 2021, national guidelines upheld race-based equations that assigned higher kidney function estimates to Black patients, delaying subspecialist referral and transplant waitlisting. In 2023, the Organ Procurement and Transplantation Network (OPTN) mandated that US kidney transplants programs submit wait time modifications for Black candidates who were disadvantaged by these equations. OBJECTIVE: To evaluate whether implementation of the OPTN wait time modification policy was associated with changes in kidney transplant rates by race and ethnicity in the US. DESIGN, SETTING, AND PARTICIPANTS: This quasi-experimental study analyzed an OPTN database of all US adult kidney candidates actively waitlisted between January 2022 and June 2025. Interrupted time series analysis evaluated the association of policy implementation with changes in transplant rates using generalized estimating equations adjusted for secular trends, time-varying and time-invariant confounding factors, and a first-order autoregressive covariance structure. Data analyses were performed from July 2024 to July 2025. INTERVENTION: Implementation of the OPTN wait time modification policy in January 2023. MAIN OUTCOMES AND MEASURES: Kidney transplant rates by race/ethnicity and dialysis status, with outcome stratification by living and deceased donor kidney transplant (LDKT and DDKT). RESULTS: The analysis included 181 314 kidney transplant candidates (mean [SD] age, 52.8 [13.1] years; 68 517 females [37.8%] and 112 797 males [62.2%]), including 56 344 Black candidates (31.1%) and 124 970 candidates of all other racial and ethnic groups (68.9%; including American Indian/Alaska Native, Asian, Hispanic/Latino, Native Hawaiian/Other Pacific Islander, White, multiracial, and unknown). From January 2023 through June 2025, 21 119 transplant candidates received wait time modifications, which added a median (IQR; range) of 1.7 (0.9-3.0; 0-21.2) years, and a total of 51 061 person-years of waitlist time. In interrupted time series analyses, among Black candidates, policy implementation was associated with an increase of 5.3 transplants per 1000 listings (95% CI, 3.5 to 7.0), with decreasing transplant rates thereafter (-0.10 transplants per 1000 listings per month; 95% CI, -0.17 to -0.03). Among all other candidates, implementation was associated with no significant change in overall transplant (0.6 transplants per 1000 listings; 95% CI, -1.8 to 0.7) and a parallel decreasing trend thereafter (-0.10 transplants per 1000 listings per month; 95% CI, -0.15 to -0.05). In secondary analyses, policy implementation was associated with increased overall and DDKT rates among Black preemptive and postdialysis candidates, no significant changes in LDKT for either group or DDKT for non-Black and/or Hispanic candidates, and a small secular increase in overall transplant rates. CONCLUSIONS AND RELEVANCE: This quasi-experimental study found that implementation of the wait time modification policy was associated with increased transplant rates among Black preemptive and postdialysis candidates. These findings provide evidence that remedying the harms of race-based medicine may be a promising approach to address racial kidney transplant inequities.
Alexander GC, Xiao X, Dilek S
… +6 more, Lewis S, Deng Q, Kim M, Bolanle D, Saldanha IJ, Mehta HB
JAMA Intern Med
· 2026 May · PMID 41770554
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IMPORTANCE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a novel class of therapeutics approved to treat chronic conditions such as cardiovascular disease, diabetes, and/or obesity. However, whether GLP-1 RA...IMPORTANCE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a novel class of therapeutics approved to treat chronic conditions such as cardiovascular disease, diabetes, and/or obesity. However, whether GLP-1 RAs' efficacy varies by age, sex, race and ethnicity, baseline body mass index (BMI), and baseline hemoglobin A1c (HbA1c) is unclear. OBJECTIVE: To quantify the heterogeneity of treatment effects (HTE) of GLP-1 RAs, including semaglutide, liraglutide, exenatide, lixisenatide, and dulaglutide, by patient characteristics. DATA SOURCES: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, from inception through July 26, 2024. STUDY SELECTION: Pairs of investigators independently screened titles and abstracts and then reviewed eligible full-text articles reporting on randomized clinical trials (RCTs) that compared GLP-1 RAs to placebo or other medications. DATA EXTRACTION AND SYNTHESIS: Study design, interventions, and comparators, and patient baseline weight and weight change over time (overall and by age, sex, race and ethnicity, BMI, and HbA1c level) were extracted from the data. Risk of bias was assessed using the Cochrane risk of bias tool and meta-analyses were conducted using random-effects models. For each subgroup, RCTs were meta-analyzed where quantitative synthesis was possible, while additional relevant studies were narratively incorporated in the analysis. MAIN OUTCOMES AND MEASURES: Change in body weight measured in kg (by age, baseline BMI, baseline HbA1c) or percentage change from baseline (by sex, race and ethnicity). RESULTS: Of 7705 unique records, 41 articles representing 64 RCTs were included in the meta-analysis. Of these, 48 RCTs could be individually characterized: they had a mean (SD) study population of 1181 (2513) participants; 51 trials were parallel (98.1%); 51 multicenter (98.1%); and 21 evaluated semaglutide (43.8%) and 9, dulaglutide (18.8%). HTE was most commonly evaluated using baseline BMI (36 RCTs [75.0%]), HbA1c (24 [50.0%]), and age (21 [43.8%]), and less commonly, ethnicity (12 [25.0%]), race (11 [22.9%]), and sex (10 [20.8%]). Among 6 trials (19 906 patients) analyzed by sex, weight loss was greater among women (10.9%; 95% CI, 7.0%-14.8%) than men (6.8%; 95% CI, 4.6%-9.0%). We found no significant HTE by age (7 trials with 4314 patients), race (9 trials, 25 229 patients), ethnicity (7 trials, 8328 patients), baseline BMI (15 trials, 9473 patients across 3 analyses), or baseline HbA1c (4 trials, 1886 patients). CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis, GLP-1 RAs produced greater weight loss among women than men; however, their efficacy was consistent across other important subpopulations. These findings may inform clinical decision-making.
Aitken D, Cai G, Hill CL
… +13 more, Cicuttini FM, Wluka AE, Wang Y, Keen HI, Thompson MJW, Asthana C, Antony BE, Wang X, Winzenberg T, de Graaff B, Buttigieg K, Otahal P, Jones G
JAMA Intern Med
· 2026 May · PMID 41770553
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Full text
IMPORTANCE: Knee osteoarthritis (OA) is disabling, with few effective treatments. Anti-inflammatory treatments may be effective for patients with an inflammatory phenotype. OBJECTIVES: To evaluate the efficacy of the int...IMPORTANCE: Knee osteoarthritis (OA) is disabling, with few effective treatments. Anti-inflammatory treatments may be effective for patients with an inflammatory phenotype. OBJECTIVES: To evaluate the efficacy of the interleukin-1β blocker diacerein, compared with placebo, on knee pain in people with knee OA who have substantial knee pain and inflammation (effusion-synovitis on magnetic resonance imaging). DESIGN, SETTING, AND PARTICIPANTS: This multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted in 4 Australian centers. Participants with clinical knee OA, substantial knee pain, and effusion-synovitis on magnetic resonance imaging were enrolled from June 2019 to September 2022. Final follow-up occurred on February 6, 2023. Data analysis began on July 7, 2023. INTERVENTIONS: Participants were randomized (1:1) to diacerein, 50 mg, once daily or identical placebo for the first 2 weeks, which increased to 50 mg, twice daily until 24 weeks if adverse effects were tolerable. MAIN OUTCOMES AND MEASURES: The primary outcome was change in knee pain as assessed by the visual analogue scale (range, 0-100 mm; minimal clinically important improvement, 15) over 24 weeks. RESULTS: Of 262 participants randomized (mean [SD] age, 54.9 [6.1] years; 147 [56.1%] female and 115 [43.9%] male), 231 (88.2%) completed the trial. Compared with placebo, diacerein did not improve knee pain over 24 weeks (-19.9 mm [diacerein] vs -18.6 mm [placebo]; between-group mean difference, -1.3 mm; 95% CI, -9.8 to 7.3). The most common adverse events were gastrointestinal symptoms, which occurred in 55 participants (41.7%) in the diacerein group and 33 (25.4%) in the placebo group, most commonly diarrhea (51 [38.6%] in the diacerein group vs 29 [22.3%] in the placebo group). Change in urine color was observed among 13 participants (9.8%) who received diacerein. CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that, in patients with symptomatic knee OA and effusion-synovitis, diacerein (50 mg, twice daily) over 24 weeks resulted in no greater improvement in knee pain compared with placebo. These findings do not support diacerein for treating knee pain in this population. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12618001656224.