Durant RW, Corbie G, Allore HG
… +15 more, Anderson TS, Brender T, Choi JJ, Ganguli I, Grady D, Gross CP, Hung A, Katz MH, Kneifati-Hayek JZ, Mody L, Richman IB, Rittenberg E, Tripodis Y, Wang TY, Inouye SK
JAMA Intern Med
· 2026 Jun · PMID 42377942
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Reddy A, Nelson KM, Geyer J
… +7 more, Gunnink E, Wheat CL, Rojas J, Berger D, Shah N, Frost MC, Schuttner L
JAMA Intern Med
· 2026 Jun · PMID 42371662
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IMPORTANCE: Screening for unhealthy alcohol use is recommended in primary care; however, completion and quality are inconsistent especially during telemedicine visits. Little is known about optimal workflows incorporatin...IMPORTANCE: Screening for unhealthy alcohol use is recommended in primary care; however, completion and quality are inconsistent especially during telemedicine visits. Little is known about optimal workflows incorporating electronic screening (e-screening). OBJECTIVE: To evaluate whether use of previsit asynchronous e-screening is associated with improved completion and detection of unhealthy alcohol use via the Alcohol Use Disorders Identification Test (AUDIT-C) questionnaire compared with usual staff-administered screening during telemedicine primary care visits. DESIGN, SETTING, AND PARTICIPANTS: Pragmatic cluster randomized quality improvement trial conducted at 2 primary care clinics in the Veterans Health Administration (VHA) from June 24 to August 1, 2024. Primary care clinicians (PCCs) were randomized 1:1, stratified by site, to intervention or control. INTERVENTION: For PCCs in the control arm, patients received usual care including staff-administered AUDIT-C at telemedicine visits. For PCCs in the intervention arm, 24 to 48 hours before visits patients additionally received an invitation to asynchronous self-administered e-screening. Veterans who did not complete e-screening were still eligible for staff completion of screening during their clinic visits. MAIN OUTCOMES AND MEASURES: The primary outcome was completion of AUDIT-C; secondary outcome was positive screen result (AUDIT-C ≥5). The exploratory outcome was brief intervention after positive screen result. All statistical models were clustered by PCC and adjusted for patient age, sex, race and ethnicity, comorbidity, prior primary care use, and site. RESULTS: Among 848 veterans in the primary analysis (mean [SD] age, 55.4 [16.1] years; 729 [86.0%] male), use of e-screening was associated with increased telemedicine visit screening completion rates by 30.5 percentage points (74.4% [95% CI, 68.5%-80.3%] for e-screening vs 43.9% [95% CI, 26.6%-61.2%] for usual care; P < .001) and with increased likelihood of a positive screen result (10.6% [95% CI, 8.0%-13.2%] for e-screening vs 2.7% [95% CI, 0.7%-4.7%] for usual care; P < .001). Exploratory analysis identified the proportion of veterans receiving a brief intervention after a positive screen result (2.3% [10 of 442] for usual care vs 5.9% [24 of 406] for e-screening; P = .01). CONCLUSIONS AND RELEVANCE: In this study, use of asynchronous e-screening was associated with improved completion and screen-positive results for unhealthy alcohol use in primary care, with the greatest gains for telemedicine encounters. Overall, this approach may close the implementation gap for population-based screening, improve disclosure, and reduce staff burden, particularly in hybrid care models. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN16316660.
Luo S, Gong Q, Ai Y
… +8 more, Zhang J, Chan L, Wong WCW, Ip P, Chan EWY, Tanuseputro P, Wong ICK, Wan EYF
JAMA Intern Med
· 2026 Jun · PMID 42371637
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IMPORTANCE: Paracetamol (acetaminophen) is the first-line analgesic and antipyretic recommended globally during pregnancy. Observational studies have reported associations with increased risks of autism spectrum disorder...IMPORTANCE: Paracetamol (acetaminophen) is the first-line analgesic and antipyretic recommended globally during pregnancy. Observational studies have reported associations with increased risks of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) in offspring, raising public and clinical concern; however, these findings may be substantially confounded by unmeasured familial factors. OBJECTIVES: To assess the association between prenatal paracetamol exposure and risk of ASD and ADHD in offspring using a sibling-matched study design to control for familial confounding. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study, conducted from January 1, 2001, to December 31, 2023, in Hong Kong, used deidentified electronic health records within a triangulation framework. From an initial cohort of 708 020 mother-child pairs (approximately 43.3% with prenatally paracetamol exposure), sibling-matched cohorts were constructed of children from families with discordant prenatal paracetamol exposure and sufficient follow-up (≥2 years for ASD and ≥5 years for ADHD). Data analysis was conducted from October 2, 2025, to March 24, 2026. EXPOSURE: Prenatal paracetamol exposure, identified from electronic dispensing records (British National Formulary [BNF], section 4.7.1) with data on drug name, strength, dosage, and prescription dates. MAIN OUTCOMES AND MEASURES: Incident diagnoses per the International Classification of Diseases, Ninth Revision, Clinical Modification, for ASD (code 299) or for ADHD (code 314) or a prescription for ADHD-specific medication licensed in Hong Kong (methylphenidate, atomoxetine, or lisdexamfetamine [BNF, section 4.4]). RESULTS: The final cohorts comprised 124 333 children for ASD analysis (mean [SD] age, 9.3 [4.7] years; 61 775 females [49.7%] and 62 558 males [50.3%]) and 97 285 for ADHD analysis (mean [SD] age, 7.6 [4.2] years; 48 455 females [49.8%], 48 830 [50.2%]). In the sibling-matched analyses, prenatal paracetamol exposure was not associated with the risk of ASD (adjusted hazard ratio [aHR], 1.00; 95% CI, 0.91-1.11) or ADHD (aHR, 1.01; 95% CI, 0.93-1.08). Null associations were consistent across exposure timing, cumulative dose, and usage patterns (sporadic, intermittent, persistent), and were robust in sensitivity analyses. However, positive associations were observed in conventional cohort analyses, and importantly, also in negative control analyses of prepregnancy exposure for ASD (HR, 1.12; 95% CI, 1.08-1.17) and ADHD (HR, 1.24; 95% CI, 1.20-1.28). CONCLUSIONS AND RELEVANCE: In this population-based cohort study, a sibling-matched analysis found no evidence of an association between prenatal paracetamol exposure and the risk of ASD or ADHD in offspring. The positive signals observed in conventional studies are likely attributable to residual familial confounding. These findings provide important reassurance regarding the safety of indicated paracetamol use during pregnancy.
Morone NE, Faurot KR, Weinberg J
… +17 more, McTigue K, Roth I, Barnhill J, Gardiner P, Thomas HN, Lathren CR, Castro MG, Baez J, Lawrence S, Harr E, Elhadidy N, White AM, Nguyen PT, Dore G, Rodriguez R, Gaylord SA, Greco CM
JAMA Intern Med
· 2026 Jun · PMID 42371634
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IMPORTANCE: Back pain is among the most common, disabling, and costly conditions managed in primary care in the US, but current treatment options often do not provide adequate relief. Mindfulness-based interventions have...IMPORTANCE: Back pain is among the most common, disabling, and costly conditions managed in primary care in the US, but current treatment options often do not provide adequate relief. Mindfulness-based interventions have demonstrated effectiveness in individuals with chronic low back pain (CLBP); however, mindfulness remains underused in part because it is not integrated into most outpatient care models. OBJECTIVE: To assess whether persons with CLBP participating in a mindfulness group medical visit intervention experience significantly improved pain intensity and interference compared with those receiving usual care. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial, Optimizing Pain Treatment in Medical Settings Using Mindfulness (OPTIMUM), using a pragmatic approach (designed to evaluate interventions under typical conditions of care) was conducted from May 7, 2021, to November 6, 2024. Adults with CLBP attending primary care clinics in Massachusetts, Pennsylvania, and North Carolina were included. INTERVENTION: Participants were randomized 1:1 to the OPTIMUM intervention, an 8-week telehealth-delivered mindfulness group medical visit program delivered as part of primary care (intervention), or usual care (controls). MAIN OUTCOMES AND MEASURES: The primary analysis assessed the between-group difference in the primary outcome of change from baseline to month 6 in the Pain, Enjoyment of Life and General Activity (PEG) scale score. A mean minimal clinically important difference (MCID) in PEG score of at least 1 was considered. Secondary analyses evaluated the between-group differences in change from baseline to week 8 and month 12 in PEG score. RESULTS: Of 451 participants (mean [SD], 52.1 [14.7] years; 318 [70.5%] female), 224 were randomized to the intervention group and 227 to the control group. All reported moderate pain interference at baseline. In intention-to-treat analyses, the intervention participants had a statistically significant improvement in PEG score from baseline compared with controls at the 6-month primary time point (mean change, -1.21 [95% CI, -1.50 to -0.92] vs -0.59 [95% CI, -0.86 to -0.31]; between-group difference, -0.62 [95% CI, -1.02 to -0.23]; P = .002) and at 8 weeks (mean change, -1.16 [95% CI, -1.44 to -0.88] vs -0.27 [95% CI, -0.53 to -0.003]; between-group difference, -0.89 [95% CI, -1.27 to -0.51]; P < .001) and 12 months (mean change, -1.52 [95% CI, -1.81 to -1.23] vs -0.78 [95% CI, -1.05 to -0.50]; between-group difference, -0.74 [95% CI, -1.14 to -0.34]; P < .001). The MCID was not met at any time point. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, a telehealth-delivered mindfulness group medical visit program for persons with CLBP resulted in significant improvements in pain intensity and interference compared with usual care; however, these changes did not meet the prespecified mean 1-point MCID between groups. The program incorporated primary care clinicians, was accessible, and is potentially scalable as a nonpharmacologic treatment for CLBP. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04129450.
Kurlander JE, Parra D, Moore V
… +9 more, Holleman R, Burns J, Midboe AM, Garlick B, Domlyn A, Chia L, Barnes GD, Kim HM, Sussman JB
JAMA Intern Med
· 2026 Jun · PMID 42329643
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IMPORTANCE: Antiplatelet medications are overprescribed in patients taking direct oral anticoagulants (DOACs), increasing their risk of major bleeding. The utility of potentially scalable antithrombotic stewardship appro...IMPORTANCE: Antiplatelet medications are overprescribed in patients taking direct oral anticoagulants (DOACs), increasing their risk of major bleeding. The utility of potentially scalable antithrombotic stewardship approaches remains unknown. OBJECTIVE: To evaluate a multicomponent antithrombotic stewardship initiative to reduce unnecessary antiplatelet use in patients prescribed DOACs. DESIGN, SETTING, AND PARTICIPANTS: This quality improvement study used retrospective multiperiod comparative interrupted-time-series analysis from July 2020 to July 2023 to compare intervention and control sites. Participants were adults prescribed DOACs in the ambulatory setting. The interventions occurred in 7 Veterans Health Administration (VHA) health systems, while 128 other VHA health systems served as controls. Data were analyzed from July 2023 to March 2026. INTERVENTION: In stage 1, lasting 9 months, intervention sites implemented educational outreach to clinicians and patients and changes to the electronic health record system. In stage 2, lasting 16 months, a clinical pharmacist-facing electronic flag identifying patients receiving antiplatelet therapy was added to a widely used electronic dashboard. MAIN OUTCOMES AND MEASURES: Monthly site-level percentage of patients prescribed antiplatelet medications. The summary measure was the difference in the semiannual change in the outcome for intervention compared with control sites, controlling for preintervention trends. Subgroup analyses were performed based on antiplatelet indication. RESULTS: This study found that preintervention antiplatelet use in patients prescribed DOACs was 26.1% (95% CI, 26.0%-26.1%) in the 7 intervention sites (27 588 patients; 704 females [2.6%]) and 30.1% (95% CI, 30.0%-30.2%) in 128 control sites (253 085 patients; 6481 females [2.6%]). Antiplatelet use decreased faster by an absolute -0.58 (95% CI, -0.95 to -0.22) percentage points (pp) per 6 months for intervention compared with control sites after the 2 interventions had been implemented. The initial set of interventions was associated with an absolute -0.29 (95% CI, -0.61 to 0.04) pp change per 6 months and later augmentation with the electronic flag was associated with an absolute -0.29 (95% CI, -0.61 to 0.03) pp change per 6 months. The combined interventions were associated with the greatest reduction in the subgroup of patients with stable coronary artery disease (absolute -2.1 [95% CI, -3.0 to -1.2] pp per 6 months, equivalent to a -5.5% additional change compared with the baseline prevalence in this group), for whom antiplatelet deimplementation is likely appropriate. CONCLUSIONS AND RELEVANCE: This study found that the combined interventions were associated with a clinically meaningful reduction in potentially harmful combination antithrombotic therapy. The initial educational outreach and changes to the electronic health record and later augmentation with the electronic flag had additive effects, highlighting the importance of multilevel interventions to speed adoption of evidence-based antithrombotic prescribing.
Hsu CY, Gao Y, Freedman BI
… +10 more, Lunn MR, Muiru AN, Schnitzler MA, Divers J, Mannon RB, Palmer ND, Karger AB, Lentine KL, Park M, Long-Term Kidney Transplantation Outcomes Network (APOLLO) Consortium
JAMA Intern Med
· 2026 Jun · PMID 42329639
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IMPORTANCE: Accurate understanding of long-term risks after living kidney donation is critical to inform evidence-based policies for donor candidate evaluation and selection. OBJECTIVE: To determine whether apolipoprotei...IMPORTANCE: Accurate understanding of long-term risks after living kidney donation is critical to inform evidence-based policies for donor candidate evaluation and selection. OBJECTIVE: To determine whether apolipoprotein L1 gene (APOL1) polymorphisms were associated with worse kidney function after living kidney donation. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included all living US kidney donors who donated from January 2000 to December 2008, whose contact information was obtained from the Scientific Registry of Transplant Recipients. After using online search tools to update addresses and telephone numbers, Black and White US living kidney donors who donated during this period were invited to participate. Enrolled study participants had home-based research visits conducted by a subcontract agency between March 2020 and March 2024. Final data analysis was conducted from April 2024 until February 2026. EXPOSURES: APOL1 polymorphisms and race. MAIN OUTCOMES AND MEASURES: The primary outcome was an estimated glomerular filtration rate (eGFR) of less than 45 mL/min/1.73 m2 by serum creatinine at the time of home-based research visits. Additional outcomes were an eGFR of less than 60 mL/min/1.73 m2, urinary albumin-creatinine levels of 30 or greater or 300 or greater mg/g, and hypertension. RESULTS: A total of 445 Black kidney donors (295 female individuals [66%]; mean [SD] age, 38 [10] years) and 208 White kidney donors (141 female individuals [68%]; mean [SD] age, 44 [10] years) were enrolled. Sixty-eight Black donors (15.3%) had APOL1 high-risk genotypes (G1/G1, G2/G2, or G1/G2). Home-based research study visits occurred a median (IQR) of 18.5 (16.9-20.5) years after donation. Forty-six of all participants (7.0%) were noted to have an eGFR of less than 45 mL/min/1.73 m2. Black kidney donors with APOL1 high-risk genotypes had a higher risk of developing an eGFR of less than 45 mL/min/1.73 m2 than Black kidney donors without APOL1 high-risk genotypes (relative risk, 2.31; 95% CI, 1.16-4.61; P = .02) (after adjustment for predonation eGFR: relative risk, 1.91; 95% CI, 0.90-4.03; P = .09). CONCLUSIONS AND RELEVANCE: The study found that the APOL1 genotype is a risk factor for reduced kidney function postdonation. These results suggest that all Black individuals who are living donor candidates in the US should undergo APOL1 genotyping for better risk stratification.
JAMA Intern Med
· 2026 Jun · PMID 42295793
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IMPORTANCE: COVID-19 vaccines were previously shown to reduce risk of major adverse cardiovascular events (MACEs). Whether the 2024-2025 COVID-19 vaccine continues to reduce COVID-19-associated MACEs in the context of ev...IMPORTANCE: COVID-19 vaccines were previously shown to reduce risk of major adverse cardiovascular events (MACEs). Whether the 2024-2025 COVID-19 vaccine continues to reduce COVID-19-associated MACEs in the context of evolving variants and widespread population immunity is unknown. OBJECTIVE: To determine whether the 2024-2025 COVID-19 vaccine is associated with reduced risk of COVID-19-associated MACE. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was a target-trial emulation using US Department of Veterans Affairs (VA) electronic health records. Participants were veterans with vaccination encounters between September 3, 2024, and December 31, 2024. EXPOSURES: Same-day coadministration of the 2024-2025 COVID-19 and influenza vaccines vs influenza vaccine alone. MAIN OUTCOMES AND MEASURES: Composite end point of COVID-19-associated MACE, defined as COVID-19-associated cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure. Secondary outcomes included all-cause MACE, hospitalization, and death. Vaccine effectiveness (VE), calculated as 1 minus the risk ratio, and risk difference were estimated at 8 months using inverse probability weighting. RESULTS: Among 1 039 659 participants who received influenza vaccine (mean [SD] age, 70.1 [12.4] years; 954 341 [91.8%] men), 349 085 received COVID-19 vaccine and 690 574 did not. At 8 months, the COVID-19 vaccine was associated with lower risk of COVID-19-associated MACE (VE, 37.7% [95% CI, 18.2%-54.9%]; risk difference per 10 000 persons, 2.0 [95% CI, 0.9-3.7]). VE for COVID-19-associated MACE was statistically significant only in individuals older than 75 years (VE, 50.7% [95% CI, 31.8%-65.6%]), a group that also experienced the largest absolute risk reduction (5.5 fewer events per 10 000 individuals). No statistically significant vaccine effectiveness was observed among those younger than 65 years or aged 65 to 75 years. While VE for COVID-19-associated MACE on the relative scale was statistically significant across subgroups of participants with and without comorbid health conditions, the absolute benefit was consistently and substantially greater for individuals with the comorbid health condition. Secondary analyses of all-cause MACE, all-cause hospitalization, and all-cause death suggested substantially larger absolute risk reductions (risk difference for all-cause MACE, 23.7 [95% CI, 14.1 to 34.7]). CONCLUSIONS AND RELEVANCE: In this cohort study, receipt of the 2024-2025 COVID-19 vaccine was associated with reduced risk of COVID-19-associated MACE, with reductions most prominent in those 75 years or older and those with comorbidities. While the reduction in COVID-19-associated MACE was modest, the substantially larger reduction in all-cause MACE suggests that the vaccine's protective association extends to the hidden burden of undetected SARS-CoV-2 and its sequelae.