JAMA

Introduction: Preeclampsia (PE) is a leading cause of maternal and neonatal morbidity and mortality, and low-dose aspirin (LDA) prophylaxis is the cornerstone of evidence-based prevention. Despite guideline recommendations, LDA adherence remains poor, with 10-25% of moderate-risk patients taking aspirin. Objective personalized risk stratification using biomarkers has been shown to motivate behavior change in other disease contexts. Survey data suggest that patients are more motivated to take aspirin if informed by an objective predictive test. Here, we report real-world LDA adherence among patients who received a high-risk result from a cell-free RNA (cfRNA) PE risk prediction test. Methods: This retrospective, observational survey study included asymptomatic patients of advanced maternal age (AMA; [&ge;] 35 years at delivery) with singleton pregnancies without USPSTF-defined preexisting high-risk conditions for PE who received the cfRNA PE risk prediction test. Patients who opted in to receive text message surveys were asked about LDA use following receipt of test results. High adherence was defined as reporting LDA use on at least 6 of 7 days per week at least 85% of the time surveyed. The primary analysis included patients with a high-risk test result and at least one LDA frequency survey response following receipt of test result. The observed proportion of adherent patients was compared to a baseline estimate of 25% using an exact binomial test. Results: Of 166 patients who received a cfRNA PE risk prediction test result, 48 (28.9%) received a high-risk result. Of these, 29 (60%) opted in and responded to at least one survey, constituting the primary analysis population. Twenty-seven of the 29 (93.1%; 95% CI: 78.0-98.1%) were classified as highly adherent, significantly higher than the 25% baseline adherence estimate for moderate-risk patients (p < 0.0001). Conclusion: Among surveyed patients who received a high-risk cfRNA PE test result, the proportion classified as highly adherent to LDA (93%) substantially exceeded published estimates of adherence in a similar patient population and met the clinically meaningful threshold of [&ge;] 80% associated with reduced risk of preterm preeclampsia. These findings indicate that objective and personalized biomarker risk testing may be a powerful driver of behavior change that current guidelines have failed to produce.

Background: The efficacy and safety of avacopan in ANCA-associated vasculitis (AAV) has been established in randomized trials of of avacopan as a glucocorticoid (GC) sparing therapy. However, real world evidence (RWE) has an important role in confirming effectiveness and evaluating safety in more generalizable settings. This study aimed to synthesize RWE on the effectiveness and safety of avacopan in adults with AAV. Methods: A systematic literature review and meta analysis of non interventional real world studies was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. Eligible studies included adults with AAV treated with avacopan in routine clinical practice. Pooled estimates of effectiveness and safety outcomes were calculated using random effects meta-analyses. Primary outcomes included remission at 6 and 12 months and sustained remission at 12 months. Secondary outcomes included relapse, GC use and dosing, hepatotoxicity, infections, and treatment discontinuation. Exploratory outcomes included changes in estimated glomerular filtration rate (eGFR) and dialysis related endpoints. Results: A total of 71 studies were included and contributed to quantitative analyses. Pooled remission for patients on avacopan was 87% (95% CI: 75%-94%) at 6 months and 93% (95% CI: 86%-97%) at 12 months, and sustained remission was 86% (95% CI: 74%-93%) at 12 months. Relapse at 12 months was low (7%; 95% CI: 4%-11%). GC use was 36% at both 6 and 12 months. Improvements in eGFR were observed at 6 months (18 mL/min/1.73 m2) and 12 months (18 mL/min/1.73 m2), and dialysis liberation was 66% in a limited subset. Among avacopan patients, 11% experienced any hepatotoxicity, including 7% with serious (defined as directly reported or requiring hospitalization) hepatotoxicity, while 7% experienced serious (defined as directly reported or requiring hospitalization) infection. Conclusions: In real world clinical practice, avacopan is associated with high remission rates, low relapse rates, and a consistent GC sparing effect, with effectiveness comparable to standard of care regimens. Findings support its clinical use with appropriate safety monitoring; however, the observed heterogeneity in hepatotoxicity and the limited comparative effectiveness evidence highlight areas requiring further investigation.

Importance: Avacopan is a small-molecule C5aR1 antagonist used as adjunctive treatment for granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Evidence of real-world clinical effectiveness and safety is limited. Objective: Compare effectiveness and describe safety outcomes of avacopan plus SoC versus SoC alone. Design: Retrospective U.S. cohort study with prevalent new-user design emulating sequential nested trials with up to 12-month follow-up. Index dates: first avacopan prescription (avacopan arm); first rituximab or cyclophosphamide claim (SoC arm) during trial window. Setting: Optum Market Clarity administrative claims (October 2015 - June 2025). Participants: Adults receiving rituximab or cyclophosphamide after newly diagnosed or relapsing GPA/MPA. Comparative effectiveness cohort: patients meeting baseline eligibility. Safety cohort: adults with an avacopan prescription, regardless of other eligibility. Interventions: Avacopan plus SoC vs SoC alone. Main Outcomes and Measures: Relapse, prednisone-equivalent daily dose (PEDD) [&le;]7.5 mg, and serious hepatic event hospitalization were prespecified, whereas cumulative oral glucocorticoid exposure was analyzed post-hoc. A strict hepatic-event screen required [1] acute/subacute hepatic failure, central hemorrhagic liver necrosis, or toxic liver disease and [2] [&ge;]1 code indicative of severe acute liver injury on the same claim; a relaxed hepatic-event screen required either criterion. Standardized mortality ratio and censoring weights accounted for baseline covariates and informative censoring. Treatment effects in the avacopan-treated population were estimated. Results: The effectiveness analysis included 183 avacopan and 4096 SoC index dates. The safety cohort had 828 avacopan users. There were 38 events of relapse in the avacopan arm and 956 in the SoC arm (weighted hazard ratio [95% CI]: 0.81 [0.59, 1.13]). PEDD [&le;]7.5 mg was numerically more common with avacopan plus SoC at most timepoints. Cumulative glucocorticoid exposure was lower with avacopan plus SoC; between-arm differences exceeded 500 mg from months 5 through 12. No avacopan-exposed patients met the strict hepatic event screen definition. Relaxed hepatic event screen events occurred in 2 (1.1%), 5 (0.6%), and 10 (0.5%) patients in the avacopan effectiveness, avacopan safety, and SoC cohorts, respectively. Conclusions and Relevance: Early evidence from claims data suggests avacopan plus SoC may reduce relapse risk and enable faster glucocorticoid tapering vs SoC alone. Serious hepatic events appear rare.

Background Racial and ethnic minority populations face disproportionate rates of uncontrolled blood pressure (BP) and hypertension-related mortality. Remote hypertension monitoring (RHM) with active clinician-led medication titration has shown promise for improving BP control, but real-world evidence in majority-minority primary care settings remains limited. Methods This retrospective cohort study (January 2022-December 2024) enrolled adults with hypertension in a Bluetooth-integrated RHM program at a single urban academic primary care clinic. Of 550 patients enrolled, 503 with evaluable follow-up data were included. Patients transmitted daily home BP readings; clinicians reviewed readings monthly and titrated anti-hypertensive regimens per 2017 ACC/AHA guidelines. BP control was assessed at baseline and 3, 6, and 9 months. Factors associated with longitudinal BP control were examined using multivariable generalized estimating equations (GEE), with outcomes defined as strict control (<130/80 mmHg), at-least-moderate control (<140/90 mmHg), and uncontrolled (>140/90 mmHg). Results Among 503 participants (mean age 58.3 [SD 12.1] years; 63.6% African American; 52.9% male), BP control increased from 10.1% at baseline to 37.1% at 9 months. Each additional month of enrollment was associated with reduced odds of uncontrolled BP (adjusted odds ratio [aOR] 0.82; 95% CI, 0.80-0.85; P<.001). White race was associated with lower odds of uncontrolled BP versus African American race (aOR 0.57, at-least-moderate control; aOR 0.40, strict control; both P<.001). Male sex (aOR 1.46; P=.02) and congestive heart failure (aOR 2.09, strict control; aOR 2.05, at-least-moderate control; both P<.05) were associated with higher odds of uncontrolled BP. Conclusion Bluetooth-integrated RHM with active clinician-led medication titration was associated with a nearly 4-fold increase in BP control over 9 months in a majority-minority primary care population. Persistent within-program racial disparities underscore the need for equity-centered strategies beyond technology adoption alone. Prospective studies with concurrent usual-care comparators are needed to establish causal inference.

Background: Avacopan, an oral complement C5a receptor inhibitor, has been shown to help patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) achieve and sustain remission with reduced glucocorticoid exposure and associated toxicity. As of January 20, 2026, estimated global post-marketing exposure exceeded 25,000 patient-years. Hepatic adverse events (AEs), predominantly liver enzyme elevations observed during clinical development, remain an important post approval safety risk. Since approval, vanishing bile duct syndrome (VBDS), a rare but serious complication of drug induced liver injury (DILI) has been reported with avacopan use. This analysis evaluated Amgen's global safety database data to characterize hepatic adverse event reports associated with avacopan, including VBDS. Methods: We conducted a retrospective descriptive analysis of hepatic AEs recorded in the Amgen global safety database. Results: As of 20 January 2026, serious hepatic AEs were reported at approximately 31 events/1,000 patient-years. The majority of hepatic events comprised laboratory abnormalities that resolved following avacopan discontinuation. Thirty-one VBDS cases were reported and, of those, 27 originated from Japan. Fatal VBDS cases were reported predominantly from Japan and occurred in patients >65 years. Conclusions: Hepatotoxicity remains an important avacopan-specific safety risk. Post-marketing data indicate that most hepatic events are reversible laboratory abnormalities; however, serious liver injury and VBDS, including fatal outcomes, have been reported, predominantly from Japan. No new safety risks have emerged from the ongoing Japanese post-marketing study. Further investigation is warranted to understand potential mechanisms underlying the disproportionate occurrence of serious VBDS events in Japanese patients and inform optimized risk-mitigation strategies.

Introduction No widely adopted guidelines exist for collecting and reporting donor-level metadata in tissue-based research, limiting interpretability, reproducibility, and potentially introducing bias. This study aimed to inform ethical and appropriate metadata practices. Methods Semi-structured interviews were conducted with 16 investigators from the Human BioMolecular Atlas Program. Thematic analysis using inductively derived codes identified metadata elements and perspectives on their collection and reporting. Results Participants identified 80 metadata variables across six domains: demographic, sociodemographic, medical history, personally identifying information, cause of death, and tissue/organ data. Most supported routine collection and reporting of demographics and medical history, whereas views on cause of death and sociodemographic data were mixed. Conclusion We recommend routinely collecting and reporting demographics and medical history, while restricting cause of death and sociodemographic variables to situations with explicit consent or justification. These findings provide initial evidence to inform ethical donor metadata guidelines, with further stakeholder engagement and consensus-building needed.

Background: Anti-synthetase syndrome (ASyS) is a subgroup of idiopathic inflammatory myopathies that is increasingly recognized as a distinct entity with features of myositis, interstitial lung disease, inflammatory arthritis, and Raynaud phenomenon. Co-reactivity with anti-Ro-52, an antibody directed against the Ro-52 E3 ubiquitin ligase, has been shown to be associated with progressive interstitial lung disease within this patient population. However, less is known regarding the association of anti-Ro-52 positivity with cardiovascular outcomes. Methods: A sub-cohort of patients with anti-synthetase antibodies at a large single institution center was retrospectively analyzed to define presence of anti-Ro-52 positivity (defined as anti-Ro-52 titer greater than or equal to 11 utilizing the line immunoblot platform, Euroline Autoimmune Inflammatory Myopathies, EuroImmun Diagnostics, Lubeck, Germany). Patients who did not meet 2017 ACR/EULAR classification criteria for idiopathic inflammatory myopathies were excluded from the final analysis. Cardiovascular outcomes ascertained via retrospective chart review included atrial fibrillation, left bundle branch block, right bundle branch block, pulmonary hypertension (confirmed via right heart catheterization), heart failure with reduced ejection fraction (HFrEF, defined as ejection fraction less than or equal to 40 percent), acute coronary syndrome (based on clinical diagnosis and angiography if available), and myocarditis (based on clinician diagnosis and either cardiac MRI or troponin elevation). When a pre-specified cardiac outcome was identified, the date of onset was recorded. Differences in proportions were analyzed via Chi-squared and Fishers exact tests, and time-to-event analyses were performed via Cox Proportional Hazards Models, incorporating a false discovery rate correction for multiple outcomes. All analyses were performed using SAS v9.4. Results: 88 patients were included in the final analysis, of whom 69 (78.4 percent) were categorized as anti-Ro-52 positive. Patients with anti-Ro-52 positivity had a higher maximum recorded serum creatine kinase (median 1297 vs 395 units per liter, p = 0.042). No significant associations between anti-Ro-52 positivity and the pre-defined cardiovascular outcomes were found over median follow up time of 12.5 years. Conclusions: In a large, single-center cohort of patients with ASyS, anti-Ro-52 positivity was not associated with an increased burden of negative cardiovascular outcomes, including the onset of pulmonary hypertension. Future studies may seek to further elucidate the mechanisms underlying the pleiotropic effects of anti-Ro-52 antibodies on the cardiopulmonary system.

Genetic testing for inherited cardiovascular conditions is recommended by multiple national guidelines to inform medical management. However, access to genetic counseling and testing is often limited particularly in the inpatient setting. Cardiologists cite lack of access to genetic counselors as a reason for not pursuing genetic testing. Genetic test education videos have been successfully implemented in the outpatient setting to increase patient volumes and decrease wait times, but they have not been studied in the inpatient setting.

Background: Diabetes is a major global public health challenge, associated with substantial medical, economic, and social burden worldwide. As clinicians working at the intersection of medicine and nutrition, we observed that despite advances in pharmacologic therapy, many individual, particularly those living in underserved urban communitie, continue to experience suboptimal diabetes control due to persistent barriers related to food insecurity, cultural food practices, and limited access to practical nutrition education. In response, we implemented a community-based pilot study in an underserved urban area that focused on dietitian-led nutrition education grounded in Food Is Medicine principles. Aims: The intervention emphasized culturally responsive, cost-conscious, and client-centred approaches designed to make healthy eating simple and intuitive, with the goal of complementing standard diabetic medical therapy. Methods: We used conventional diabetic marker responses, fasting blood sugar (FBS), HgbA1c (percentage of glycosylated hemoglobin, subsequently documented as A1c), and urinary albumin:creatinine ratio (UACR) in a dual cohort design study measuring whether groups receiving dietitian-led nutrition education in addition to conventional therapy would show improvements in diabetic markers relative to groups receiving conventional therapy alone. Summary: Our pilot study summed over both cohorts support the hypothesis that additional dietitian-led nutrition education synergizes with conventional pharmaceutical therapy to improve diabetic control as gauged by improved FBS, A1c and UACR, implying a significant role for this combined approach to community based diabetic health care.

Introduction Accurate measurement of blood loss after caesarean birth is important for early identification of postpartum haemorrhage. Commonly used visual estimation underestimates blood loss. We compared two methods for objectively assessing blood loss. Methods Measured blood loss was obtained by weighing swabs and pads combined with blood from suction and drapes. Calculated blood loss was derived from maternal weight and peripartum haemoglobin change. Data were from the I'M WOMAN trial investigating tranexamic acid for postpartum haemorrhage prevention. This was a secondary analysis of prospectively collected trial data. We reported median (IQR) blood loss, assessed agreement using Bland-Altman analysis and compared the percentages of women exceeding 500 ml, 1000 ml and 1500 ml. We graphed proportional haemoglobin drop by categories of measured blood loss, stratified by anaemia status. We compared AUCs for measured and calculated blood loss predicting haemodynamic compromise (shock index above 1.0) and death or near-miss. Results A total of 10,393 women were included in this study. Median measured and calculated blood loss were 545 ml (IQR 430-700) and 505 ml (IQR 180-908) respectively, with weak correlation (Spearmans rho=0.28). The IQR was wider for calculated blood loss than for measured blood loss, indicating greater variability. Bland-Altman analysis showed a small mean bias of -39 ml but wide limits of agreement (lower -1196 ml, upper 1118 ml). Measured versus calculated blood loss exceeded 500 ml in 60% versus 51% of women, 1000 ml in 7% versus 21%, and 1500 ml in 2% versus 8%. Women without anaemia had a greater proportional haemoglobin drop than women with anaemia for blood losses below 1000 ml. Measured blood loss had better predictive ability for death or near-miss (AUC 0.87 vs 0.76, p<0.001) and haemodynamic compromise (AUC 0.66 vs 0.62, p=0.001). Conclusion While median measured and calculated blood losses were similar, they were only weakly correlated. Calculated blood loss classified more women as having blood loss above higher thresholds. Women without anaemia had a greater proportional haemoglobin drop than women with anaemia for blood loss below 1000 ml. Measured blood loss had a modest advantage in predicting death or near-miss and haemodynamic compromise, but calculated blood loss remains an objective measure suitable as a trial outcome when direct measurement is not feasible.

The US spends more on health care than any other nation, yet tens of millions of Americans are uninsured or underinsured, and coverage retractions enacted in 2025 are widening these gaps. The misalignment between the for-profit insurance architecture and optimal patient care, together with the inefficiencies of a fragmented system, contributes to both unnecessary costs and preventable mortality. We update our previous analyses with the most recent data to project the economic benefits and the number of lives saved that would be achieved by single-payer universal coverage, as proposed in the Medicare for All Act. We estimate that such a system would reduce national health expenditure by $1,041 billion annually. Sources of savings include reductions in administrative overhead, pharmaceutical prices, fraudulent billing, and avoidable emergency care. Combined with the reversal of recent retractions, universal coverage would save over 114,000 lives annually.

Respiratory syncytial virus (RSV) contributes to substantial morbidity and mortality in young children each year. In 2023, two new prevention products were licensed and recommended in the United States (US), including a prefusion F protein subunit vaccine (RSVpreF) administered during pregnancy and a long-acting monoclonal antibody (mAb) administered in infants. Although post-licensure real-world studies support the effectiveness of RSVpreF vaccine during pregnancy, existing studies have been conducted in settings where only RSVpreF vaccine is available. The real-world effectiveness of RSVpreF vaccine in settings where both RSVpreF vaccine and mAbs are available is not yet well understood. The goal of this study is to estimate the real-world effectiveness of the RSVpreF vaccine against severe infant RSV by applying causal mediation analysis with receipt of mAbs as a mediating variable. Using a national cohort of mother-infant dyads with the Optum Labs Data Warehouse (OLDW), we will model vaccine and mAb effects in a longitudinal cohort spanning the 2023-24, 2024-25, and 2025-26 RSV seasons. Results will be used to better understand the total effect of RSVpreF vaccination when it is used as one component within a hybrid infant RSV prevention program.

Background: The 2026 American Heart Association/American College of Cardiology (AHA/ACC) guidelines replaced the 2019 European Society of Cardiology (ESC) four-tier pulmonary embolism (PE) risk scheme with five clinical categories (A-E) and subcategories. These categories were set by expert consensus and have not been validated against outcomes. How patients are reclassified relative to ESC, or how the two systems compare prognostically, is unknown. Methods: We utilized three cohorts of patients with confirmed PE using structured electronic health record data, laboratory biomarkers, and large-language-model abstraction of radiology reports: Duke University Health System (n=12,992, drawn from 95,760 consecutive inpatient CT pulmonary angiography studies, 2014-2025, with no referral or registry enrollment step between imaging and cohort entry), INSPECT (Stanford; n=3,870), and MIMIC-IV (Beth Israel Deaconess; n=361). Patients were assigned AHA/ACC categories B through E, subcategorized where data allowed, and mapped to 2019 ESC risk strata. The primary outcome was 30-day mortality; discrimination was assessed with Harrell C-index. Results: Among 17,223 patients with confirmed PE, pooled 30-day mortality rose monotonically across categories: 1.5% (B), 8.9% (C), 15.5% (D), and 31.9% (E), with the ordering preserved in all three cohorts despite differing baseline mortality. Subcategory-level discrimination was reliable only at the high-acuity extreme (D2-E2); across subcategories C1 through D1, mortality did not order monotonically (9.2%, 10.8%, 8.1%, 10.9%), and adding subcategories to category C did not improve discrimination at Duke (C-index 0.699 vs 0.699). Category C patients lacking both echocardiography and biomarker testing (12.7% of category C) had mortality (10.4%) equal to or exceeding classified peers. Relative to ESC, the frameworks were concordant at the extremes, but 5.7%of ESC intermediate-risk patients were reclassified to category D, with modestly higher but non-significant 30-day mortality than those remaining in category C (10.8% versus 8.9%). Conclusions: Across a three-health-system cohort, the 2026 AHA/ACC framework produced a reproducible mortality gradient at the category level, with added subcategory granularity refining risk chiefly at the highest-acuity tiers. Discrimination across the broad intermediate band was limited, and reclassification from ESC fell almost entirely within this range.

Importance: Hereditary breast and ovarian cancer (HBOC) variant carriers benefit from risk-reducing interventions, but only if identified. The extent to which carriers are clinically recognized, and whether recognition is equitable across diverse populations, is poorly characterized in a single large U.S. cohort. Objective: To estimate P/LP HBOC carrier prevalence across genetic ancestry groups, quantify documented clinical genetic testing among carriers, and evaluate ancestry and socioeconomic disparities in testing. Design, Setting, and Participants: Cross-sectional analysis of the All of Us Research Program Controlled Tier (Curated Data Repository v8/C2024Q3R9), comprising participants with short-read whole genome sequencing and linked electronic health record (EHR) and survey data. Carriers were ascertained from research genomic data independent of clinical testing. Exposures: Genetically inferred ancestry (African [AFR], Admixed American [AMR], East Asian [EAS], European [EUR], Middle Eastern [MID], South Asian [SAS]); self-reported household income and educational attainment. Main Outcomes and Measures: (1) Carrier prevalence with Wilson 95% CIs; (2) documented clinical genetic testing (procedure codes) among carriers; (3) adjusted odds of documented testing among women, by ancestry, before and after socioeconomic adjustment, using multivariable logistic regression. Results: Among 414,830 participants, P/LP HBOC carrier prevalence was 1.42% (95% CI, 1.38-1.45) overall and similar across ancestry groups (AFR 1.24%, AMR 1.32%, EAS 1.19%, EUR 1.52%, MID 1.68%, SAS 1.33%; overlapping CIs). Among 250,071 women in the testing analysis, documented clinical genetic testing was rare: only 74 of 5,878 carriers overall (1.3%) and 59 of 3,572 European-ancestry carriers (1.7%) had a documented test, with counts below reportable thresholds in all other ancestry groups. African-ancestry women had lower adjusted odds of documented testing than European-ancestry women (Model 1 adjusted odds ratio [aOR], 0.32; 95% CI, 0.27-0.39), an association that attenuated but persisted after adjustment for income and education (Model 2 aOR, 0.48; 95% CI, 0.40-0.58; P < 0.001); Admixed American women also had reduced adjusted odds (aOR, 0.71; 95% CI, 0.61-0.84). Lower income and lower education were independently and dose-dependently associated with lower testing odds (income <$25,000 aOR, 0.46; high-school education aOR, 0.54). Conclusions and Relevance: High-risk HBOC variant carriers are present across all ancestry groups at similar frequencies, yet documented clinical genetic testing was disparate in the different ancestry groups. African-ancestry women experience a testing gap that is not fully explained by socioeconomic position, implicating structural barriers in access and referral. Population-level strategies that decouple carrier identification from current referral pathways may be required to close this gap.

Objective: To determine whether and to what extent hospitals across the United States vary in their use of late-preterm steroids using a novel data set in which the timing of steroid administration relative to delivery can be observed. Methods: This was a retrospective cohort study of singleton births with known gestational ages identified in the Premier Healthcare Database from 2015 to 2022. The primary variable of interest was hospital-level adoption of antenatal corticosteroids for late-preterm singleton deliveries, calculated as the proportion of late-preterm singleton births (34-36 completed weeks of gestation) with any betamethasone exposure during the same late-preterm period. Hospital adoption was defined as the weighted average rate of ALPS administration among late-preterm infants across the entire post-period. Hospitals were ranked by their late-preterm steroid adoption rates and categorized by quartile based on the empirical distribution. Temporal trends were assessed using annual hospital-level adoption rates and visualized using time-series plots and distributional plots. A logistic regression model was constructed to determine hospital characteristics associated with being a highest-quartile adopting hospital. Results: The analysis cohort included 728 hospitals and 5,452,791 births, of which 361,006 (6.6%) were singleton late preterm births. Hospital steroid exposure rates ranged from 0 to 82% and were categorized into quartiles based on overall exposure rate, with cutoffs at 20.6%, 29.8%, and 40.1%. Median exposure rates increased progressively across quartiles from 14.1% (IQR 9.3-17.4%) in the lowest adopting hospitals (Q1) to 47.6% (IQR 43.7-53.2%) in the highest adopting hospitals (Q4), with substantial within-quartile variation. In the multivariable model, urban location was a strong predictor of high adoption after adjustment (aOR 2.05; 95% CI 1.11-3.83, p=0.02). Compared to Midwest hospitals, Southern hospitals had significantly lower odds of being high adopters (aOR 0.37; 95% CI 0.20-0.69, p<0.01). Among clinical case mix variables, a higher proportion of late preterm births at 34 weeks' gestation was strongly associated with high adoption (aOR 2.21; 95% CI 1.58-3.14, p<0.001). Conclusion: Following publication of the ALPS Trial, there was heterogeneous adoption of late preterm steroids among US hospitals. These findings highlight the need for a more in-depth exploration of local factors that drive the adoption of evidence-based practices outside of observable hospital characteristics.

Genetic testing for cardiomyopathy and arrhythmia (CM/ARRH) provides diagnostic information and informs screening for at-risk relatives. Clinical guidelines recommend genetic testing for these conditions; however, data on how genetic test results influence clinical management recommendations are limited. Here, we determined the frequency of cardiologist-recommended management changes for patients following CM/ARRH genetic testing. This was a retrospective cross-sectional study of patients referred for multigene panel testing between April 2016 and April 2024. Genetically-experienced cardiologists at multicenter academic clinical practices were recruited for participation to complete surveys indicating clinical decision making on patients who had genetic testing. Cases for review were randomly selected to have both positive and non-positive results. Among 249 patients (138 positive, 111 non-positive), 136 (54.6%) received clinical management recommendations for their own or their at-risk relatives? care. Of these, 75 (55.1%) received recommendations for the patient?s own care, most frequently additional diagnostic tests/procedures (n=33). Compared to non-positive results, patients with positive results were more likely to receive recommendations for their own management (66/138, 47.8% vs 9/111, 8.1%; P<0.00001). Patients with positive results in arrhythmogenic cardiomyopathy genes had 263% higher odds of recommended management changes compared to those with TTN (OR=3.63, CI:1.40-9.84, P=0.009). The results from CM/ARRH genetic testing on affected patients influenced cardiologists? medical decision making and management recommendations. Additional research is needed to evaluate how genetic testing for CM/ARRH impact health outcomes.

Background The phase 3 ADVOCATE trial evaluated the efficacy and safety of avacopan in patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Concerns raised regarding the 2019 primary endpoint adjudication process prompted a blinded, independent readjudication of all participants' primary outcomes, the results of which are described here. Methods Patients with GPA or MPA were randomized 1:1 to receive oral avacopan 30 mg twice daily or oral prednisone on a scheduled taper, each in combination with rituximab- or cyclophosphamide-based standard of care. In 2026, the Duke Clinical Research Institute Clinical Events Classification group conducted an independent, blinded committee re-adjudicated the Birmingham Vasculitis Activity Score (BVAS), relapse, and remission from weeks 26 through 52 using procedures aligned with the original adjudication charter. The primary endpoints were remission at week 26 and sustained remission at week 52. As per the original analysis plan, noninferiority and superiority were declared if the lower bounds of the 95% confidence interval (CI) for the difference in the primary outcome rates between avacopan and a prednisone taper were greater than -20.0 and 0.0 percentage points, respectively. Results Among 330 participants in the intent-to-treat population, remission at week 26 was achieved by 68.1% (113/166) and 67.1% (110/164) of participants in the avacopan and prednisone taper groups, respectively, in the 2026 readjudication (adjusted difference: 2.2%; 95% CI, -7.5, 11.9), compared with 72.3% (120/166) and 70.1% (115/164) in the 2019 primary outcome adjudication (adjusted difference: 3.4%; 95% CI, -6.0, 12.8). Sustained remission at week 52 was achieved by 61.4% (102/166) and 52.4% (86/164) of participants, respectively, in the 2026 readjudication (adjusted difference: 9.8%; 95% CI, -0.3, 19.9), compared with 65.7% (109/166) and 54.9% (90/164) in the 2019 readjudication (adjusted difference: 12.5%; 95% CI, 2.6, 22.3). Concordance between the 2019 and 2026 adjudications was 95.2% for remission and 93.6% for sustained remission. Conclusion The re-analysis of ADVOCATE based on the 2026 readjudication further supports the efficacy of avacopan for GPA/MPA. Non-inferiority of avacopan versus a prednisone taper was confirmed at weeks 26 and 52 despite a median 81% reduction in glucocorticoid exposure observed in the avacopan versus prednisone taper groups. While a consistent numerical difference favoring avacopan at week 52 was observed in the 2019 and 2026 analyses, this difference did not reach statistical superiority.

Objective: Genomic research using electronic health record (EHR)-linked biobanks is influenced by heterogeneity in the clinical settings (care sites) where encounters occur. We developed two methods leveraging care site data: ClinicScan identifies where phenotype documentation occurs, and ClinicWAS identifies specialty utilization patterns associated with a risk factor. Materials and Methods: We extracted care sites for each clinical encounter at an academic medical center and mapped each to a clinical specialty. ClinicScan summarizes the specialty distribution of a user-specified diagnosis; ClinicWAS fits a logistic regression for each care site to identify specialty encounters associated with a user-specified risk factor. We applied ClinicScan to depression to test whether requiring a psychiatry encounter strengthened the association between a polygenic risk score (PRS) and a depression phenotype, and ClinicWAS to a coronary heart disease (CHD) PRS to identify sites enriched for high-risk patients. Results: Across 64,983,257 encounters, 2,544 care sites mapped to 57 specialties. Most depression diagnoses occurred in primary care (30.3%) and psychiatry (19.8%). Requiring a psychiatry encounter strengthened the PRS-phenotype association (OR=1.30, 95% CI 1.26-1.35) versus two or more diagnosis codes alone (OR=1.21, 95% CI 1.19-1.24). CHD ClinicWAS identified 19 associated care sites, including 5 catheterization labs. Men and women with high genetic risk (PRS[&ge;]95th percentile) underwent catheterization for CHD 3.1 (1.5-4.6) and 4.6 (2.5-6.7) years earlier than normal-risk participants, respectively. Discussion: Care site data capture phenotype heterogeneity that otherwise distorts EHR-based phenotypes and obscures high-risk subpopulations. Conclusion: Clinical care site data are an under-utilized resource in EHR-linked biobanks.

Purpose As genomics permeates all healthcare specialties, genetic counseling in conjunction with genetic testing is broadly recommended. Improving access to genetics professionals is crucial for Americans insured by Medicaid. The purpose of this study was to conduct a comprehensive review of Medicaid policies for genetic counseling performed by Certified Genetic Counselors (CGC(C)). Methods Fee-for-service Medicaid policies across 50 states and Washington DC were reviewed and coded. Four states with exemplary policies were identified, and CGC managers in two of these were surveyed regarding the real-world effects of these policies. Results As of 2024, 20 states (39%) had a published policy for genetic counseling with most (N=16, 80%) expressly covering genetic counseling in connection with any covered genetic test. Of the states without a policy, 12 (24%) mention genetic counseling in the context of scenario-specific policies, and 19 (37%) have no published policy. Twenty states explicitly cover CGC services, while 2 exclude CGCs as service providers. CGC managers in Indiana and Michigan confirmed the policies identified as exemplary successfully led to reimbursement of CGC services. Conclusion There is significant variability in Medicaid coverage for genetic counseling. Comprehensive policies are needed to support patient access to genetics professionals, including CGCs.

Dyslipidemia is a significant risk factor for cardiovascular disease (CVD), the leading cause of death in Samoa, accounting for 34% of deaths. Polygenic scores (PGS) derived from large scale multi ancestry genome-wide association studies offer potential for improved CVD risk prediction by aggregating genetic effects on lipid traits, yet their performance in Pacific Islander populations remains largely unknown. We evaluated the transferability of multi-ancestry PGS for LDL cholesterol (LDL C), HDL cholesterol (HDL C), triglycerides (TG), and total cholesterol (TC) in 4,342 Samoan adults across five cohorts spanning 1990 to 2010. PGS derived from Graham et al. and Kanoni et al. multi-ancestry meta-analyses were harmonized with genome-wide imputed genotypes using a Samoan-specific reference panel, and performance was assessed using incremental R^2 from linear mixed models with bootstrapped confidence intervals. PGS performance varied across traits and cohorts: HDL C showed the highest performance (incremental R^2 5.0 to15.0%), followed by LDL C (5.7 to 8.6%) and TC (5.0 to10.7%), with TG showing the lowest performance (3.5 to 7.0%). Meaningful LDL C transferability was achieved only when using a genome-wide PRS CS score (99.6 to 99.7% variant matching), whereas a curated pruning-and-thresholding score achieved only ~9% matching and near-zero performance. These findings establish the first systematic benchmarks for lipid PGS performance in Samoans, demonstrate that multi-ancestry scores can achieve meaningful transferability in this underrepresented population when genome-wide variant coverage is ensured, and highlight the importance of rigorous variant harmonization assessment prior to clinical deployment of PGS in diverse populations.