JAMA

Background: The observational literature on comparative effectiveness is expanding rapidly but remains difficult to synthesize. Discordant findings often stem from structural differences in cohort definitions, inclusion criteria, and follow up windows, leaving stakeholders without a cohesive evidence base. Furthermore, studies typically focus on a narrow subset of outcomes, neglecting the broader needs of diverse healthcare stakeholders 1,2,3,4. Methods We developed a high throughput evidence generation workflow using linked EHR and administrative claims data. The cornerstone is a prespecified measurement architecture applied uniformly across clinical scenarios: six post index windows (acute to two year follow.up); 28 Elixhauser comorbidities; 14 healthcare resource utilization (HCRU) categories; 29 laboratory measures with 52 binary thresholds; and 42 adverse event categories. We generated unadjusted treatment comparisons across ~1,038 outcomes per scenario, including effect-measure modification (EMM) assessments across 130 baseline features. Results Across 40 clinical domains, the workflow produced approximately 32,982,552 outcome evaluations. An evaluation included a treatment comparison outcome population effect estimate with uncertainty bounds and supporting diagnostics. Approximately 5,000 narrative summaries underwent structured clinical and statistical quality control before dissemination. Conclusions Standardized, high throughput workflows can shift evidence generation away from fragmented studies toward comprehensive evidence packages. This shared evidence base supports precision medicine by making treatment effect heterogeneity visible across clinically meaningful subpopulations, reducing the need for redundant, stakeholder-specific studies.

ObjectivesArtificial intelligence (AI)-enabled digital stethoscopes combine phonocardiography and electrocardiography to support detection of cardiac rhythm and structural abnormalities. This study evaluated the feasibility and exploratory diagnostic performance of AI-guided cardiac auscultation during routine general practice consultations and home visits. MethodsIn this prospective feasibility study, 50 consecutive patients aged [≥]65 years underwent AI-assisted auscultation using the Eko CORE 500 during routine care. Recordings were attempted at four standard cardiac positions. Feasibility outcomes included technical failure, workflow disruption, and proportion of analyzable recordings (defined as successful AI output based on combined ECG and phonocardiography signals). Exploratory diagnostic performance was assessed against previously established diagnoses of atrial fibrillation (AF), heart failure (HF), or valvular heart disease (VHD) documented in the electronic medical record. ResultsAI-guided cardiac auscultation was completed in all patients without device malfunction or meaningful workflow disruption (median acquisition time 1-2 minutes). At least one analyzable recording was obtained in 47/50 patients (94%), and complete four-position analyses in 42/50 (84%). Signal limitations were mainly attributable to obesity, chest hair, or excess breast tissue. Among 47 analyzable patients, 11 had known AF, HF, or VHD. Sensitivity for detecting these conditions was 81.8% and specificity 91.7%. One new case of clinically relevant mitral regurgitation was identified. ConclusionsAI-enabled digital auscultation was feasible in routine general practice, with high rates of analyzable recordings and minimal workflow impact. Larger studies with contemporaneous reference standards are warranted to determine clinical utility.

Purpose: We systematically reviewed the evidence for three questions on screening for lung cancer with computed tomography (CT): benefits (from randomized trials) and harms of screening versus no screening/minimal intervention or alternative screening approaches (e.g., selection criteria, screening intervals); relative importance that informed patients place on the potential benefits and harms of screening (patient preferences); and comparative effects from observational studies of different screening selection criteria (using risk prediction models) or nodule classification systems compared with those used in the screening trials. Methods: A working group of primary care and specialist clinicians (previously members of Canadian Task Force on Preventive Health Care) and topic experts provided input into the eligibility criteria and key potential effect moderators, rated outcomes for their importance to decision making, and developed decision thresholds for use when making conclusions and assessing certainty of the evidence. Critical outcomes of screening effects included all-cause mortality, lung-cancer mortality, and overdiagnosis (via excess cancer incidence from screening). For patient preferences, we sought direct preference data via (i) disutilities of relevant health states (measuring their impact on ones health-related quality of life on a scale of 0 [perfect health] to 1 [death], mainly using EQ-5D), and (ii) other preference-based data, such as outcome trade-offs, as well as indirect preference data via (iii) the relative importance of benefits versus harms inferred from attitudes, intentions, and behaviors towards screening among eligible patients informed with estimates of the outcomes. For screening benefits and harms and for patient preferences, we searched three databases (MEDLINE, Embase, and Central & MEDLINE, Scopus, and EconLit, respectively) to July 11, 2025. For screening studies published prior to 2015 we relied on searches for other reviews, and for patient preferences our search was limited to 2012-onwards. For comparative effects, we searched MEDLINE and Embase from 2019 to September 23, 2025, with reliance on other reviews for studies published 2012-2018. Reference lists were scanned and trial registries searched. For the main searches, two independent reviewers screened titles and abstracts and then full texts; for search updates we applied AI to assist with title and abstract screening. Data extraction and analysis were undertaken by single reviewers, with verification; risk of bias and GRADE certainty assessments were undertaken independently by at least two reviewers. Data were pooled where suitable using random effects methods appropriate to the outcome metric and prevalence. Subgroup analyses explored heterogeneity (e.g., sex, number of rounds, type of comparator, sensitivity of nodule management, type of utility measurement). When not pooled (e.g., patient preferences based on screening intentions) data were analyzed by grouping studies based on factors such as population, setting, exposure, and outcomes, with consideration of study size and risk of bias. Conclusions and certainty assessments for screening effects were based on estimates of absolute effects. Results: We included 85 studies (N=640,537; 13 trials) on screening benefits and harms, 59 on patient preferences (33 [N=42,219] on disutilities and 26 [N=10,829] other studies), and 16 for comparing trial (National Lung Screening Trial [NLST]) and LungRADs nodule management, either directly (2 studies, N=26,978) or indirectly (14 studies, N=1,102,285). Screening benefits and harms: Findings from nine trials (N=94,530) examining low-dose CT (LDCT) screening on all-cause (RR 0.97, 95% CI 0.93 to 1.01; 3.7 fewer [8.5 fewer to 1.2 more] per 1000) and lung-cancer mortality (RR 0.87, 95% CI 0.79 to 0.96; 4.0 fewer [1.2 to 6.4 fewer] per 1000) offered low and moderate certainty, respectively, that screening previous/current 20-30 pack-year smokers 50-74 years old 3-4 times will probably result in at least 1 (all-cause) and 2 (cause-specific) fewer deaths per 1000 screened after 10-12 years. The absolute effects may not apply to participants at the lowest baseline risk for lung-cancer incidence (e.g., <1.5% over 6 years) or death. Seven trials (N=35,161) contributed to meta-analysis for overdiagnosis (RR 1.19, 95% CI 1.03 to 1.37; 8.4 [1.3 to 16.3] per 1000), and our certainty was moderate that LDCT screening 3-4 times will probably result in at least 2.5 cases of overdiagnosis per 1000 screened over 10 years. For important outcomes, we had high certainty that screening 3-4 times results in at least 75 people per 1000 screened (and probably at least 225) having at least one benign biopsy/false positive, 150 having one or more incidental findings (likely at least 450), and 50 (probably at least 100) having a clinically significant/actionable incidental finding, but probably does not have an important impact on major complications or death from invasive testing among those without cancer. Though undergoing a LDCT scan probably causes little-to-no psychosocial harm, having a positive screening result likely causes at least a small degree of harm (i.e., 4-8% change from baseline), especially for the 10-15% having to undergo invasive procedures where some may experience moderate harm. Among those without cancer, these effects may last for several months while the diagnostic process is underway, though moderate certainty evidence found little-to-no effects remaining after 6 months from diagnostic resolution. Comparative effects: Findings from applying different baseline predicted risks for lung-cancer incidence or mortality to the trial populations (i.e., alternative selection criteria) were considered with the effects from screening benefits and harms. Using LungRADs instead of NLST nodule management (among NLST eligible people) probably reduces the false positive rate substantially (about half), though the number of false positives still exceeded the decision threshold of 75 per 1000 and the effects for benefits or other harm outcomes are not known. Patient preferences: Findings showed little-to-no disutility (i.e., <0.04) from a positive screening test (moderate certainty) or a false positive result (low certainty). Low-certainty evidence found there may be little-to-no disutility from a stage I-IIIA cancer diagnosis (before treatment) but small but important disutilities from a stage IIIB/IV diagnosis, during first-line treatment of any stage (though possibly moderate disutility of about 0.09 for stage IIIB/IV), and after treatment for stage IIIB/IV but not stage I-IIIA (without progression) where effects were inconsistent but indicated that any disutility may not be long-lasting. Findings for stage I-IIIA are likely most relevant for understanding the consequences of overdiagnosis. For stated preferences between outcomes, there was low certainty evidence that a small majority (51-75%) of people may accept 69-122 false positives and at least 1.3 cases of overdiagnosis per prevented lung-cancer death, and think that the reduction in lung-cancer mortality is more important than experiencing one of the relevant harms. After being informed about anticipated benefits and harms from screening (with the largest screening effects shown to those at higher baseline risk), progressively more people preferred screening (mainly via intentions) as the net benefit of screening improved from low [25-50% preferred] to moderate [51-75%] to high [>75%]. Conclusions: This review provides contemporary data on the benefits and harms of LDCT screening after at least a decade of follow-up and makes conclusions based on absolute effects while considering thresholds for decision making. Across the reviews, findings indicate that screening those aged 50-74 years with 3-4 rounds of LDCT will lead to benefits and harms for which a majority, but not all, eligible people probably find acceptable and worthwhile. While current nodule management using LungRADs likely reduces false positives, whether it impacts the benefits of screening is less certain and worth further research. Further, comparative prospective studies are lacking to determine the effects from screening for those not meeting the minimum age (50 years) and smoking history criteria in the trials, despite having an equivalent risk for lung cancer.

BackgroundHypertension guidelines recommend the use of automated BP devices over manual devices to reduce observer bias, such as terminal digit preference. We aimed to evaluate systematic differences in BP readings and the association with incident stroke according to type of measurement. MethodsUsing de-identified electronic health record data from Optum Labs Data Warehouse from primary care visits in 2024, we classified providers BP measurement method using proportion of odd terminal digit preference as a proxy for manual devices (defined as <0.5% odd digits) and automated devices (defined as 45-55% odd digits). Patients from the manual and automated groups were matched on demographic and clinical covariates. We evaluated cross-sectional BP distributions by measurement modality, and compared mean BP and proportions meeting clinical thresholds using t-tests, and chi squared tests, respectively. In a separate 2019 cohort created using the same methods, we evaluated whether longitudinal associations between systolic BP and incident stroke differ by measurement method. ResultsAmong 336,634 matched patients, mean SBP in the automated group was 131.7 (19.3) mmHg and 125.9 (14.8) mmHg in the manual group. The absolute percentage of patients meeting BP clinical thresholds differed substantially (<130/80: automated 33.2% vs. manual 38.8%; <140/90: automated 61.2% vs. manual 70.9%). Among 686,482 matched patients in the 2019 cohort, the manual group had a 1.16-fold (1.10-1.22) higher risk of stroke at any given BP compared to the automated group. ConclusionManual BP measurement was associated with lower mean BP, BP control, and potential underestimation of stroke risk.

Smoking Cessation Efforts for Patients with Asthma and COPD IntroductionSmoking cessation can alter the natural history of both COPD and asthma by reducing the frequency and severity of exacerbations and slowing disease progression. Accordingly, the Global Initiative for Asthma and the Global Initiative for Chronic Obstructive Lung Disease recommend that clinicians address smoking cessation at every visit using counseling and pharmacotherapy. MethodsThe Mount Sinai Health System includes seven hospitals and more than 400 outpatient locations in the New York metropolitan area, all using a unified electronic medical record (Epic). De-identified data from calendar year 2024 were extracted for individuals identified as current smokers via the EMR smoking status tool. Patients with asthma and/or COPD were identified using ICD-10 codes. Tobacco treatment was defined as receipt of counseling or pharmacotherapy, including varenicline, bupropion, or nicotine replacement therapy. ResultsAmong 961,997 patients, 58,566 (6.1%) were identified as current cigarette smokers. Across all health system encounters, 32.6% of smokers with both asthma and COPD were given any treatment, followed by 26.7% of smokers with COPD, 13.0% of smokers with asthma, and 9.9% of cigarette smokers without these conditions. Smokers seen in pulmonary clinics were the most likely to be given treatment (17.4%), followed next by primary care (6.6%).The most commonly used treatment for all cohorts and all treatment settings was nicotine with the exception of the pulmonary clinic where varenicline predominated. DiscussionDespite higher treatment rates among smokers with asthma and COPD, only one-third of those with either condition received cessation treatment over a full year, underscoring the need for sustained system-wide quality improvement efforts.

BackgroundJournals may respond to integrity concerns by publishing an editorial response (editorial notice, expression of concern (EoC) or retraction). We investigated whether the type of editorial response affected citation rates. MethodsWe obtained citations for 172 randomised controlled trials (RCTs) with integrity concerns (41 had editorial notices, 38 EoCs and 23 retractions) and control RCTs from the same journal and year. Monthly citation rates up to 60 months before and after editorial responses were compared by editorial response type, and to citation decline in control RCTs. Results172 RCTs had 10,603 citations from 6,376 articles. 3,330 control trials were identified for 151/172 RCTs (15,948 citations, 87,811 articles). For both groups, citations increased steadily, peaking 45-65 months post-publication. There were no statistically significant differences in citation decline post-editorial response for trials receiving a retraction, EoC, or notice. Citations were lower in controls than index trials, so analyses were restricted to 1598 highly cited (>25) controls. The rate of decline for highly cited control trials was not statistically significantly different from the post-editorial response rate for index groups. ConclusionCitation rate decline after editorial responses did not differ by type of editorial response nor from the natural decline in control trials. HighlightsO_LIJournals may respond to integrity concerns by issuing an editorial notice. C_LIO_LIThe effect of expressions of concern or other editorial notices on citation patterns is unclear. C_LIO_LIEditorial notices did not accelerate citation decline compared with control trials. C_LIO_LIThe type of notice was not associated with differences in citation decline. C_LIO_LILate editorial notices appear ineffective in preventing continued citation. C_LI

BackgroundPlatelet count and C-reactive protein (CRP) are blood tests commonly used in primary care as part of diagnostic work up for symptomatic patients. Abnormal results of these tests can indicate an undetected cancer; however, it is not known whether the association between an abnormal test result and cancer risk varies by patient ethnicity. MethodsThis cohort study used routinely collected primary and secondary health care records in England with linkage to national cancer registry data. Included patients had a record of ethnicity, no prior malignancy, a platelet count or CRP record between 1st January 2010 and 31st December 2017, and were aged 40 years or over at the time of that test. Ethnicity was categorised as White, Asian, Black, Other, and Mixed. Multi-level logistic regression models estimated cancer incidence within one-year of testing, adjusted for age, sex, comorbidities, BMI, deprivation, and year of test. ResultsAmong 4,948,342 patients with a platelet record and 811,559 with a CRP record, one-year cancer incidence was highest among White patients and lowest among Asian patients. Following a normal platelet count, cancer incidence was 1.3% (95% CI 1.3-1.3%) for White patients and 0.63% (0.60-0.66%) for Asian patients; following thrombocytosis, incidence increased to 4.1% (4.0-4.2%) and 1.8% (1.5-2.0%), respectively. After a normal CRP result, cancer incidence was 1.5% (1.4-1.5%) for White patients and 0.79% (0.71-0.88%) for Asian patients, rising to 3.6% (3.5-3.7%) and 1.9% (1.7-2.2%) for a high CRP result, respectively. No significant interactions were found between ethnicity, blood test result, and overall cancer diagnosis, and similar diagnostic odds ratios (dOR) were observed across all ethnic groups. However, for colorectal cancer, Black patients with abnormal results showed higher diagnostic odds ratios (dOR) compared with White patients, relative to a normal result. The dOR for thrombocytosis was 11.1 (7.8-15.6) for Black patients versus 5.7 (5.4-6.0) for White patients (interaction p-value <0.001), and for raised CRP was 4.1 (2.6-6.6) for Black patients versus 2.5 (2.3-2.7) for White patients (interaction p-value=0.043). ConclusionThis large primary care study underscores the need for ethnically diverse cohorts when evaluating diagnostic tests to avoid widening healthcare inequalities.

Background: Previous recommendations on screening for prostate cancer relied on ongoing trials of screening with prostate-specific antigen (PSA), which may have lacked sufficient follow-up duration to fully examine effects on mortality and overdiagnosis. Findings which consider absolute effects by age and screening intensity, along with newer guidance for assessing evidence certainty, may lead to different interpretations. Adding magnetic resonance imaging (MRI) to PSA-based screening has been raised as a way to reduce false positives (FPs) and overdiagnosis. Methods: We systematically searched MEDLINE, Embase, and Central from 2014 to January 28, 2026, for randomized controlled trials (RCTs) and prospective observational studies of: (i) screening versus no screening and (ii) sequential screening with MRI for those with a positive PSA test versus PSA alone among men not known to be at high risk for prostate cancer. Studies on screening with PSA or digital rectal examination (DRE) published pre-2014 were identified from existing systematic reviews and reference lists. Studies on FPs and complications from biopsies after PSA screening did not require a control group. Paired reviewers screened titles/abstracts (assisted with artificial intelligence) and full texts, assessed risk of bias, and extracted data, by age when available. We pooled data when suitable using random-effects models, investigated heterogeneity, and assessed the certainty of evidence using GRADE with conclusions of effects based on decision thresholds based on absolute effect sizes. Results: Across both questions, we included 15 RCTs (N=856,000; 8 sites of ERSPC considered separate trials) and 8 observational studies (N=56,122). At 20 years, among 1000 men who underwent repeated PSA-based screening every 2-4 years starting from age 55-69 (mean 62), there is likely a reduction in prostate-cancer mortality ([&ge;]2 fewer) and metastatic cancer incidence ([&ge;]6 fewer), at the expense of prostate-cancer overdiagnosis ([&ge;]24 cases) and FPs ([&ge;]150 cases) (all moderate certainty). If screening starts at age 50-54 or age 55, the benefits are probably smaller (e.g., 1 vs. 2 fewer prostate-cancer related deaths) with similar harms. Adding DRE or screening with PSA annually does not add benefit. One round of PSA screening or starting screening later at age 70-74 may not offer any important benefit or harm (low to moderate certainty), and any benefit from screening primarily with DRE was not shown. Compared with PSA alone, sequential screening with PSA followed by MRI reduces FPs ([&ge;]33 fewer) and overdiagnosis (via [&ge;]10 fewer diagnoses of clinically insignificant [e.g., Gleason 6] cancers without impacting detection of clinically significant cancers) (moderate to high certainty), though findings were limited to one round of screening without long-term follow-up or measurement of mortality. Interpretation: This review provides clinicians and other interest holders with anticipated absolute effects by age, and assessments of certainty across critical and important outcomes and with approximately two decades of follow-up. Findings apply to a general population and may differ for specific groups. Results for most critical outcomes, both benefits and harms, exceeded thresholds for clinically important effect sizes, thereby demonstrating the complexity of guideline developers' and patients' decision-making regarding screening trade-offs. Findings about adding MRI for those with a positive PSA test were limited and would require additional consideration of costs, infrastructure, expertise, and equity. Protocol registration: PROSPERO - CRD420250651056.

Systematic reviews are used in academia, biotechnology, pharmaceutical companies and government to synthesise and appraise large numbers of publications. The current (largely manual) workflow takes an average of 9-18 months1, at a cost of $100,000+ per review2. We built a platform, ScholaraAI, that leverages artificial intelligence to cut this to < 0.1% of the time, without compromising quality. ScholaraAI facilitates end-to-end systematic reviews; search, screening, data extraction, and analysis. The workflow is transparent, and the researcher is in the loop. Our approach is compliant with the PRISMA and RAISE frameworks. Compared to a benchmarking set of published systematic reviews, ScholaraAIs sensitivity for correctly included studies is 100% {+/-} 0%, its specificity for correctly excluded studies is 90.8 {+/-} 8.6%, and its accuracy for data extraction is 98.0 {+/-} 3.5%. The time taken per review was 3.67 hours {+/-} 1.26. We used ScholaraAI to produce a novel, up-to-date systematic review and meta-analysis, which is presented here. ScholaraAI is free to try at app.scholara.ai.

ObjectiveTo evaluate whether hyaluronan-enriched transfer medium improves live birth rates in biopsied euploid blastocyst transfers and to examine the role of zona pellucida disruption in mediating this effect. DesignRetrospective cohort study. ParticipantsA total of 1,221 single frozen euploid blastocyst transfers performed between January 2011 and December 2024. InterventionEmbryo transfer using hyaluronan-enriched transfer medium compared with standard zwitterionic-buffered transfer medium. All embryos underwent trophectoderm biopsy resulting in zona pellucida disruption. Main Outcome MeasuresLive birth rate. Secondary outcomes included biochemical pregnancy and clinical pregnancy rates. ResultsHyaluronan-enriched transfer medium was associated with significantly higher live birth rates compared with standard medium (59.1% vs. 43.2%; absolute difference 15.9%, 95% confidence interval 10.3%-21.5%; relative risk 1.37, 95% confidence interval 1.22-1.54; P < 0.001). Clinical pregnancy and biochemical pregnancy rates were also significantly higher in the hyaluronan group (P < 0.001 for both comparisons). Sensitivity analysis restricted to first transfers per patient (n = 715) confirmed persistence of the live birth benefit (61.2% vs. 47.1%; absolute difference 14.1%, 95% confidence interval 6.9%-21.3%; relative risk 1.30, 95% confidence interval 1.13-1.49; P < 0.001). Maternal age was comparable between groups. ConclusionUse of hyaluronan-enriched transfer medium is associated with a clinically meaningful increase in live birth rates in biopsied euploid blastocyst transfers. Zona pellucida disruption created during trophectoderm biopsy may facilitate enhanced embryo-endometrial interaction, improving implantation efficiency.

ObjectiveWe report secondary histologic and high-risk HPV (hrHPV) outcomes from the Acceptability and Feasibility of Combination Treatment for Cervical Precancer Among South African Women Living with HIV (ACT 2) Trial. MethodsWe conducted a double-blind Phase 2b feasibility trial of loop electrosurgical excision procedure (LEEP) combined with adjuvant intravaginal 5-fluorouracil (5FU) cream. Women living with HIV (WLWH) and cervical intraepithelial neoplasia (CIN) 2/3 underwent LEEP and were randomly assigned (1:1) to receive 8 doses of 5FU or placebo cream. Our secondary outcomes were (a) regression of cervical disease and (b) clearance of hrHPV. ResultsFrom March 2023 to January 2025, 180 participants underwent LEEP and were randomized to 5FU or placebo cream. Median age was 41 years (IOR: 35-45), 29% had HPV16, 18% had HPV18/45; 99% of women were virologically suppressed (<200 copies/mL) and median CD4 count was 636 cells/uL (IOR: 376-873). 172 participants (95.6%) completed follow-up. At week 24, 96.3% (78/81) in the 5FU group and 82.0% (73/89) in the placebo group regressed to CIN1 or normal histology (PD 14.3%, CI 5.3%, 23.3%). Among participants with positive LEEP margins at week 0, 88.0% (22/25) in the 5FU versus 61.3% (19/31) in the placebo group regressed to CIN1 or normal (PD 26.7%, CI 5.4%, 48.1%). Genotype-specific hrHPV clearance was similar in both groups (5FU: 58.0%, 40/69; Placebo: 53.8%, 43/80; PD 4.2%, CI -11.7%, 20.2%). ConclusionClinical outcomes from our Phase 2b trial demonstrates that intravaginal 5FU post-LEEP may be a beneficial adjuvant treatment for CIN2/3. Clinical Trial RegistrationNCT05413811

Background As part of Singapore's effort towards precision medicine tailored to Asian diversity, we describe the implementation of a nationwide reproductive carrier screening program. Using a customised 112-gene panel, incorporating population-specific recessive genetic diseases, we outline the overall program design, and initial efforts of community and stakeholder engagement, to inform culturally appropriate implementation. Methods Participants receive culturally tailored online education regarding our reproductive screening program and are provided results with genetic counselling and reproductive options. Community and stakeholder perspectives were assessed through questionnaires and consultations with religious leaders. Results Recruitment is nation-wide, and since initiation of our pilot phase in September 2024, 1,619 couples have registered interest, with 60% uptake of those deemed eligible. Among the 456 couples that have received results to date, four couples (0.9%) were identified to be at increased risk. Community questionnaire responses (n=1002), involving couples who participated in the program as well as the general public, indicated interest is high (59%) across the cohort but awareness, intent to participate and implications for reproductive options differed by sociodemographic factors such as ancestry and religion. Healthcare professional respondents (n=113) acknowledged carrier screening will be routine in medical care, but report limited confidence and resources. Engagement with religious leaders indicated support for the program. Conclusion These early program outcomes and community engagement are guiding the implementation of expanding population-based carrier screening in Singapore, contingent on addressing practical challenges through equitable outreach and professional training.

BackgroundMaternal participation in neurodevelopmental research involving neuroimaging and diverse biological samples is essential for understanding prenatal influences on early brain development, yet willingness in low-resource settings remains underexplored. MethodWe surveyed 300 mothers using a structured questionnaire to assess willingness to undergo brain health testing (with a focus on electroencephalography [EEG] and brain magnetic resonance imaging [MRI]), provide biological samples (blood, stool, urine, breast milk, placenta, amniotic fluid, vaginal/nasal fluid, saliva, tears), and consent to 10-year storage. Responses were analysed to examine associations between maternal sociodemographic factors and willingness to consent for each research component. ResultsNinety-two percent of participants expressed willingness for brain health testing, including [~]82% and [~]88% interest in EEG and MRI, respectively, even for untreatable conditions. Self-reported histories of foetal defects (5.3%) and birth defects (7.3%) were notably low. Biospecimen acceptance was highest (>95%) for routine samples (blood, stool, urine) but significantly low for sensitive specimens (breast milk, placenta, amniotic fluid: 51-55%) including (vaginal fluid, saliva, tears: 16-47%). Higher levels of maternal education consistently predicted consent across modalities, while being in a relationship increased willingness for stool, urine, placenta, amniotic fluid, MRI, and EEG. Low income reduced uptake for placenta, amniotic fluid, MRI, and EEG. Only 48% consented to 10-year storage of images and samples for future research. ConclusionThis study demonstrates high maternal willingness for neurodevelopmental research involving brain health testing and routine biospecimens in a low-resource setting. The findings highlight the feasibility of such protocols in a low-resource setting while exposing persistent inequities that risk underrepresenting disadvantaged mothers in maternal-child brain research. Contextually tailored consent models and capacity-building initiatives will be essential to ensure equitable, sustainable engagement across diverse LMIC populations.

Introduction Cesarean delivery accounts for nearly one-third of U.S. births and is associated with substantial maternal morbidity and health care costs. Persistent racial disparities have been documented, yet the structural factors contributing to these differences remain incompletely understood. The extent to which insurance coverage shapes racial disparities in cesarean delivery remains unclear. Objective To evaluate the independent and interactive associations of race/ethnicity and insurance coverage with cesarean delivery in the United States. Methods Population-based retrospective cohort study using singleton live births recorded in the United States Vital Statistics Natality files from 2014 to 2024. Multivariable logistic regression was used to estimate the independent effects of race/ethnicity and insurance status on cesarean delivery, including interaction terms to test effect modification, using national birth certificate data. Models were adjusted for maternal demographics, clinical factors, and temporal covariates. Adjusted odds ratios, predicted probabilities, and absolute risk differences were derived from post-estimation marginal effects. The main outcome measure was cesarean delivery (yes vs no). Results Among 41,543,568 deliveries from 2014 to 2024, 13,312,221 (32.0%) were cesarean deliveries. After adjustment, both race and ethnicity and insurance status were independently associated with cesarean delivery. Compared with non-Hispanic White women, non-Hispanic Black women had higher odds of cesarean delivery (odds ratio [OR], 1.22; 95% CI, 1.22-1.23). Relative to uninsured women, those with private insurance had 59% higher odds of cesarean delivery (OR, 1.59; 95% CI, 1.58-1.60). Significant interaction effects were observed, indicating that insurance coverage modified racial and ethnic differences in cesarean delivery. Non-Hispanic Black women had the highest predicted probabilities across all insurance categories, with the largest absolute disparities observed among uninsured women. Conclusion Racial and ethnic differences in cesarean delivery persist in the United States and are modified by insurance coverage, suggesting that coverage-related differences may contribute to inequities in obstetric care.

Background Open health data repositories receive billions in public funding, yet no systematic framework exists to evaluate their downstream scholarly impact, the composition of the research communities they cultivate, or the breadth of disciplines they reach. We introduce a two-degree citation methodology to quantify knowledge diffusion from open data, normalized by funding, and apply it to four major health data repositories. Methods Using the OpenAlex bibliometric database (January-February 2026), we identified all first-degree citing publications (n = 30,049) and their second-degree citing publications (n = 485,396), defined as papers citing those first-degree publications, for MIMIC (versions I-IV; retrospective EHR data; $14.4M), UK Biobank (prospective cohort with genomics; $525.5M), OpenSAFELY (federated EHR platform; $53.7M), and All of Us (prospective national cohort with biobanking and community engagement; $2,160M). We extracted author demographics (gender via Genderize.io, institutional country income via World Bank 2024 classifications) and research topics. Chi-square tests with odds ratios assessed demographic differences across repositories. Results Funding-normalized first-degree papers per $1M ranged from 689 (MIMIC) to 1 (All of Us), though these figures reflect total program investment, which included community engagement and biobanking for prospective cohorts in addition to data-curation costs. The citation amplification ratio was consistent across these four repositories (9.3-11.5x). Author demographics differed significantly (p < 0.001): LMIC authorship ranged from 41.8% (MIMIC) to 4.3% (All of Us), while female authorship showed the opposite pattern, lowest for MIMIC (31.8%) and highest for All of Us (43.2%). Female authors were consistently underrepresented in senior (last-author) compared with first-author positions across all repositories. Differences in scope, design, and what funding covers limit direct comparisons. Conclusions Open health data generates a consistent ~10x indirect citation amplification beyond its direct users, a ratio that held across repositories spanning over two orders of magnitude in funding. The large differences in funding-normalized output partly reflect structural differences between retrospective databases and prospective cohorts. Low-cost access combined with intentional community building attracted globally diverse research communities with LMIC investigators in intellectual leadership positions, while a persistent gender gap in senior authorship across all repositories reflects disciplinary and structural inequities that data access policies alone cannot address. Future evaluations of open data investments should examine who is producing research, from where, in what positions, and whether their participation translates into locally relevant knowledge production.

BackgroundArtificial intelligence and machine learning (AI/ML) are among the fastest-growing domains in NIH research funding, but whether children have shared equitably in this expansion is unknown. We characterized pediatric representation in NIH AI/ML funding from fiscal years (FY) 2020 to 2024. MethodsNIH grant data were obtained from Research Portfolio Online Reporting Tools Expenditures and Results bulk files for FY2020 to FY2024. AI/ML grants were identified using the NIH Research, Condition, and Disease Categorization "Machine Learning and Artificial Intelligence" category, and pediatric grants using the "Pediatric" category. Subprojects were excluded. Grants were deduplicated within each fiscal year by core project number for trend analyses and across all years retaining the most recent fiscal year for cross-sectional totals. Disease areas were identified by keyword searches of titles and abstracts. ResultsAcross FY2020 to FY2024, 5,624 unique NIH AI/ML grants totaling $3,371 million were identified. Of these, 836 grants (14.9%) were classified as pediatric, representing $401 million (11.9%) of total NIH AI/ML funding. Although this share was consistent with the historically reported overall NIH pediatric funding baseline of approximately 10% to 12%, it remained substantially below the US pediatric population share of approximately 22%. The pediatric share of NIH AI/ML funding declined from 12.3% in FY2020 to 10.8% in FY2024, despite growth in absolute pediatric funding. Indexed to FY2020, pediatric AI/ML funding grew approximately 2.6-fold compared with 3.0-fold growth in the total portfolio. Across disease areas, unadjusted adult/general-to-pediatric funding ratios ranged from 2.0-fold in mental health to 9.8-fold in cancer. ConclusionsPediatric representation in NIH AI/ML funding remained low and declined over time as the overall portfolio expanded. These findings suggest that growth in NIH AI/ML investment has not been matched by proportional gains for pediatric research.

ObjectiveTo evaluate the analytical and clinical performance of fetal fraction (FF) enriched genome-wide noninvasive prenatal testing (GW-NIPT) for detection of clinically relevant copy number variants (CNVs) down to 1 Mb. MethodsWe retrospectively analyzed 10,501 singleton pregnancies tested with FF enrichment-based GW-NIPT between August 2023 and July 2025. CNV analysis was performed using BinDel and WisecondorX. ResultsFF enrichment increased median FF to 24% (2.4-fold increase). Clinically relevant CNVs, including microdeletions and microduplications, were reliably detected down to 1 Mb. Performance was robust across all maternal body mass index (BMI) categories. The retest rate was 0.95%, resulting in a final no-call rate of 0.03% with no BMI-attributable failures. The workflow demonstrated high sensitivity, specificity, and positive predictive value for common aneuploidies, rare autosomal trisomies, sex chromosome aneuploidies, subchromosomal CNVs, and pathogenic mitochondrial DNA variants. ConclusionsFF enrichment enhances the analytical resolution of first-trimester GW-NIPT, enabling reliable detection of subchromosomal CNVs down to 1 Mb across diverse patient populations. This approach broadens the scope of prenatal screening while maintaining low test failure rates. All positive findings require confirmatory diagnostic testing and appropriate genetic counseling.

Background: Artificial intelligence chatbots (AICs), as a form of generative artificial intelligence (AI), are increasingly being considered for use in scholarly peer review to assist with tasks such as identifying methodological issues, verifying references, and improving language clarity. Despite these potential benefits, concerns remain regarding their reliability, ethical implications, and transparency. Evidence on how medical journal peer reviewers perceive the role and impact of AICs is limited. This study explored reviewers' familiarity with AICs, perceived benefits and challenges, ethical concerns, and anticipated future roles in peer review. Methods: We conducted a cross-sectional online survey of medical journal peer reviewers. Corresponding author information was extracted from MEDLINE-indexed articles added to PubMed within a two-month period using an R-based approach. A total of 72,851 authors were invited via email to participate; those who self-identified as peer reviewers were eligible. The 29-item survey assessed familiarity with AICs and perceptions of their benefits and limitations in peer review. The survey was administered via SurveyMonkey from April 28 to June 16, 2025, with two reminder emails sent during the data collection period. Results: A total of 1,260 respondents completed the survey. Most participants were familiar with AICs (86.2%) and had used tools such as ChatGPT for general purposes (87.7%), but the majority had not used AICs for peer review (70.3%). Most respondents reported that their institutions do not provide training on AIC use in peer review (69.5%), although many expressed interest in such training (60.7%). Perceptions of AIC benefits were mixed, while concerns were widely shared, particularly regarding potential algorithmic bias (80.3%) and issues related to trust and user acceptance (73.3%). Conclusions: While familiarity with AICs is high among medical journal peer reviewers, their use in peer review remains limited. There is clear interest in training and guidance, however, concerns related to ethics, data privacy, and research integrity persist and should be addressed before broader implementation.

Background: Cardiac rehabilitation (CR) is a cost-effective, evidence-based intervention that improves outcomes for patients with heart failure (HF), yet access remains inequitable, particularly among Medicaid enrollees. This study evaluates the state-by-state variability in Medicaid coverage for CR services and examines the implications for health equity in vulnerable populations. Methods: We conducted a cross-sectional policy analysis of all 50 U.S. states to assess Medicaid coverage for outpatient CR services billed under CPT codes 93797 (without ECG monitoring) and 93798 (with ECG monitoring). Publicly available Medicaid documents were reviewed and supplemented with direct communication with state Medicaid agencies. States were categorized into full, partial/inconclusive, or no coverage. Geographic trends were visualized through heat maps and contextualized using state-level Medicaid enrollment data. Results: Marked disparities in CR coverage were identified. Only 41 states reimbursed for CPT 93797, and 43 for CPT 93798. Eight states lacked coverage for either code, predominantly in the South and Mountain West, including Arkansas, Georgia, Louisiana, Mississippi, Nevada, and Utah. States with the highest Medicaid enrollment (e.g., Louisiana, Arkansas) often provided no CR coverage, compounding access barriers for high-risk, low-income populations. Conclusions: The absence of standardized Medicaid coverage for CR contributes to systemic inequities in cardiovascular care, disproportionately impacting disadvantaged communities. Aligning Medicaid policies to ensure universal CR access--particularly through tele-rehabilitation and value-based care models--could reduce hospitalizations, improve survival, and promote health equity across the U.S.

BackgroundThe sharing of data generated through the course of clinical genetic and genomic testing without explicit patient consent is increasingly important for timely diagnosis and treatment. While many jurisdictions permit the sharing of identifiable data for direct patient care, institutional policies vary in how clearly they specify key elements. When do policies permit sharing of data without explicit consent? What data types may be shared, with whom, and under what safeguards? Greater clarity around these elements may support responsible data sharing while balancing timely care with transparency and appropriate protections. MethodsWe conducted a qualitative content analysis of data-sharing and privacy policies from 33 clinical genomic institutions across 17 jurisdictions. Using a predefined analytical framework, we assessed how policies document key governance elements relevant to sharing without explicit consent. Two independent reviewers extracted information about clinical contexts, data types, justifications, and protections, documenting areas of inconsistency across institutions. ResultsAlthough 70% of institutions described circumstances permitting data sharing without explicit consent, most policies did not clearly define the scope or governance of such sharing. Policies also rarely distinguished clinical from research or secondary use and inconsistently specified privacy and security safeguards. While sharing was commonly justified for clinical care (78.3%) or testing services (43.5%), recipient roles, access conditions, and onward-sharing expectations were often left undefined. ConclusionThis uneven documentation could make it difficult for clinical teams, laboratories, and institutional decision-makers to identify and justify key decisions about what is permitted and under what conditions. A guidance framework specifying core policy elements and corresponding protections could help institutions communicate their governance choices more clearly while supporting more comparable baseline practices for responsible data sharing across settings.