This cohort study analyzes mental health trajectories before and after experiences of sexual harassment and abuse among young adults.
Importance The impact of sex on the efficacy of immune checkpoint inhibitors (ICIs) in curative treatments of solid tumors remains insufficiently explored. Optimal timing of ICIs is clinically relevant, with practice shifting toward broader adoption of neoadjuvant approaches. Objective To assess the association of patient sex and treatment timing with outcomes of ICI administration in curative treatments for solid tumors. Data Sources In this systematic review and meta-analysis, MEDLINE, Embase, the Cochrane Library, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform were systematically searched from January 1, 2010, to June 23, 2025, using controlled vocabulary combined with free-text search terms. A manual search in PubMed was conducted through August 10, 2025. Study Selection Reports of randomized phase 3 clinical trials investigating ICI treatment in non–sex-specific solid cancer types in curative settings, including surgery and radiotherapy or chemoradiotherapy as local therapies, were included. Data Extraction and Synthesis Three authors were involved in data abstraction; data from each record were extracted independently by 2 of these 3 authors. Hazard ratios (HRs) and corresponding 95% CIs were calculated using random-effects meta-analysis. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Main Outcomes and Measures Pooled HRs for overall survival (OS) and for time to the combined end point of disease-free, event-free, progression-free, and recurrence-free survival were analyzed overall, by sex, and by treatment timing relative to surgery. Results A total of 62 reports of 38 trials comprising 31 721 patients (29.7% female and 70.3% male) were analyzed. ICIs were associated with improvement in OS (HR, 0.83; 95% CI, 0.79-0.89; P < .001) and the combined end points (HR, 0.73; 95% CI, 0.68-0.77; P < .001). No statistically significant sex-specific differences were observed for OS (females: HR, 0.76 [95% CI, 0.67-0.86]; males: HR, 0.78 [95% CI, 0.72-0.85]) or the combined end points (females: HR, 0.74 [95% CI, 0.69-0.79]; males: HR, 0.73 [95% CI, 0.67-0.78]). Neoadjuvant or perioperative ICIs were associated with better OS (HR, 0.77 [95% CI, 0.69-0.86]) and combined end point outcomes (HR, 0.64 [95% CI, 0.57-0.73]) compared with adjuvant-only use (OS: HR, 0.84 [95% CI, 0.78-0.91]; combined end points: HR, 0.74 [95% CI, 0.68-0.81]). Conclusions and Relevance This systematic review and meta-analysis detected no statistically significant difference in survival outcomes associated with ICIs by patient sex, although female patients were underrepresented. In exploratory analyses, neoadjuvant or perioperative ICIs were associated with superior survival outcomes compared with strictly adjuvant administration, a finding that supports increased adoption of neoadjuvant ICI therapy approaches.
Importance Anemia is a prevalent condition among patients with traumatic brain injury (TBI); however, the optimal hemoglobin (Hb) threshold to initiate red blood cell transfusion (RBCT) is not well defined. Objective To assess which of 2 different Hb thresholds for guiding RBCT in patients with anemia and TBI is associated with a more favorable neurological outcome. Design, Setting, and Participants This was a preplanned secondary analysis of the Transfusion Strategies in Acute Brain Injured Patients multicentric randomized clinical trial, conducted in 72 intensive care units across 22 countries between September 1, 2017, and December 31, 2022. Follow-up was completed June 30, 2023. Only patients with TBI were included in the present analysis, conducted from February to May 2025. Interventions Liberal (transfusion at Hb <9 g/dL [to convert to g/L, multiply by 10.0]) vs restrictive (transfusion at Hb <7 g/dL) RBCT strategy over a maximum of 28 days. Main Outcome and Measures The primary outcome was the occurrence of unfavorable neurological outcome, defined as a Glasgow Outcome Scale Extended score of 1 to 5 (overall range, 1-8, with higher scores indicating more favorable outcome) at 180 days. In addition, 14 prespecified serious adverse events, including infection and cerebral ischemia, were assessed. Data were analyzed using both the intention-to-treat and per-protocol principles. Results Of 486 patients who presented with TBI (mean [SD] age, 46.8 [17.6] years; 347 [71.4%] male), 475 were included in the primary outcome analysis: 236 were randomized to the liberal transfusion strategy group and 239 to the restrictive transfusion strategy group. Both groups had similar baseline characteristics. In total, 534 RBCTs were administered in the liberal transfusion strategy group, compared with 246 RBCTs in the restrictive group. At 180 days after randomization, 138 patients (58.5%) in the liberal group had unfavorable neurological outcome compared with 161 patients (67.4%) in the restrictive group (relative risk [RR], 0.86 [95% CI, 0.75-1.00]; P = .047; fragility index = 1). There were no significant differences in the occurrence of secondary outcomes (eg, 28-day mortality: 42 of 240 [17.5%] vs 51 of 244 [20.9%]; RR, 0.84 [95% CI, 0.58-1.21]; P = .34) or serious adverse events (eg, RR, 1.13 [95% CI, 0.88-1.43]; P = .34 for infection and RR, 0.87 [95% CI, 0.40-1.90]; P = .72 for cerebral ischemia). After adjustment for several confounders, being randomized to the liberal group was associated with a lower observed probability of unfavorable neurological outcome (odds ratio, 0.60 [95% CI, 0.38-0.94]; P = .03). Conclusions and Relevance In this secondary analysis of a multicenter randomized clinical trial, a liberal RBCT strategy was associated with a lower risk than a restrictive RBCT strategy of unfavorable neurological outcome at 180 days among patients with TBI. These findings should be interpreted with caution in light of the inherent uncertainty of the estimate. Trial Registration ClinicalTrials.gov Identifier: NCT02968654
This cross-sectional study examines the prevalence of met and unmet prenatal breastfeeding goals and describes and compares individuals with or without these outcomes in a sample of adults who gave birth at full term.
Importance Late-onset sepsis in preterm infants is predominantly defined by bacteremia. Although binary classifications are critical for pathogen epidemiology and antibiotic stewardship efforts, they limit more granular understanding of the severity or organ dysfunction trajectory as experienced by individual infants. Objective To quantify the heterogeneity of illness severity and organ dysfunction during late-onset sepsis episodes in preterm infants. Design, Setting, and Participants Multicenter cohort study of first episodes of late-onset single-pathogen bacteremia in infants at 33 weeks’ gestation or less at 4 academic neonatal intensive care units (January 2012 to February 2025). Main Outcomes and Measures Neonatal Sequential Organ Failure Assessment (nSOFA) scores were calculated hourly from 48 hours before the index blood culture through 14 days after episode onset or death. Organ dysfunction trajectories, magnitude of change, severity, cumulative illness burden, and tempo (onset timing and topography) of burden accumulation across episodes were characterized, including those attributed to the same pathogen. Results This study identified first episodes of late-onset bacteremia in 221 preterm infants (median gestational age, 27 weeks [IQR, 25-29 weeks]; birth weight, 840 g [IQR, 650-1210 g]; 116 [52%] male). Organ dysfunction at evaluation was frequently minimal among survivors (median nSOFA, 1; IQR, 0-3), yet subsequent trajectories varied markedly across episodes. Organ dysfunction change over time (median change in nSOFA of 3 [IQR, 0-6] and 0 [IQR, 2-7] by Gram stain, negative vs positive), peak severity (median maximum nSOFA of 6 [IQR, 1-9] and 3 [IQR, 0-9] by Gram stain), cumulative burden (median cumulative nSOFA of 311 [IQR, 0-666] and 238 [IQR, 0-531] by Gram stain), and temporal dispersion (70% minimum coefficient of variation) showed wide variability across episodes, even among those of the same pathogen. By 168 hours, cumulative burden remained highly dispersed, with some survivors accumulating minimal burden and others reaching substantial burden (median cumulative nSOFA, 250 hours [IQR, 0-600 hours]) as early as 24 hours. Conclusions and Relevance In this cohort study of late-onset single-pathogen bacteremia in infants at 33 weeks’ gestation or less, late-onset bacteremia in preterm infants was associated with substantial heterogeneity in the severity and temporal course of critical organ dysfunction. Characterization of organ dysfunction dynamics may provide a more informative framework for studying neonatal sepsis than binary microbiologic classifications alone.
Importance:The use of tele-mental health (MH) care is widespread, with approximately half of all MH visits occurring remotely within the US Department of Veterans Affairs health system. However, little is known regarding the relative quality of video, phone, and in-person MH care. Objective:To study the comparative effectiveness of MH care delivered via video, phone, and in-person. Design, Setting, and Participants:This retrospective comparative effectiveness study used administrative data for all patients who completed at least 3 outpatient MH appointments during the assignment period from July 2021 to October 2022. Each participant was assigned to a MH modality cohort based on how they received most of their outpatient care in the assignment period: by video, phone, or in-person. Outcomes were assessed over a 1-year follow-up period from 2022 to 2023. Data were analyzed from July 2024 to July 2026. Exposures:Receiving most outpatient MH care via video, phone, or in-person. Main Outcomes and Measures:Outcomes of interest were MH hospitalizations, MH emergency department (ED) visits, suicide behaviors, and percentage of completed appointments. Inverse probability-weighted regression adjustment was used to obtain an average treatment effect (ATE). Results:The cohort included 813 699 participants (672 833 [82.7%] male; 354 686 participants [43.6%] aged ≥60 years), including 305 189 participants (37.5%) who received most of their MH care in person, 343 543 participants (42.2%) who received most of their care via video appointments, and 164 967 participants (20.3%) who received most of their care via phone appointments. Overall, 3027 video group participants (0.9%), 6547 in-person group participants (2.1%), and 2584 phone group participants (1.6%) experienced an MH hospitalization; 5237 video group participants (1.5%), 8009 in-person group participants (2.6%), and 3713 phone group participants (2.3%) had an MH ED visit; and 3539 video group participants (1.0%), 3780 in-person group participants (1.2%), and 2086 phone group participants (1.3%) exhibited suicidal behaviors. Video group participants completed a mean (SD) of 71.1% (21.7%) of appointments, compared with 68.0% (22.2%) of appointments in the in-person group and 68.4% (23.2%) of appointments in the phone group. The expected probability of MH hospitalization was 0.005 (SE, 0.001) points lower if all patients had received mostly video care instead of phone and 0.005 (SE, <0.001) lower vs in-person care . The same pattern emerged for MH ED visits and suicide behaviors, with expected probabilities being lower for the video group compared to phone (MH ED visit: ATE, -0.006; SE, 0.001; suicidal behavior: ATE, -0.003; SE, <0.001) or in-person (MH ED visit: ATE, -0.005; SE, <0.001; P < .001; suicidal behavior: ATE, -0.001; SE, <0.001) groups. By contrast, the expected percentage of appointments completed was 4.1 (SE, 0.1) percentage points higher in the video group vs phone group and 3.6 (SE, 0.1) percentage points higher in the video group vs in-person group. Conclusions and Relevance:In this comparative effectiveness study, receiving MH care via video was associated with improved clinical outcomes compared with receiving care via phone or in-person. Findings of possible advantages of video- over phone-based care could impact care modality decision-making if video is a feasible option. Video-based care also was associated with improved outcomes compared with in-person care. However, despite controlling for imbalanced groups, there is still potential confounding, and the magnitudes of the ATEs were small; therefore, results must be interpreted with caution.
Importance:Blinatumomab, a novel immunotherapy administered as a 28-day continuous infusion, has fundamentally shifted the treatment paradigm for pediatric B-cell acute lymphoblastic leukemia (B-ALL) and is now considered a component of standard therapy for the most common childhood cancer. However, the care delivery challenges in transitioning from an experimental agent on a clinical trial to widespread clinical implementation are unknown. Objective:To characterize the clinical landscape of pediatric blinatumomab care-delivery practice and challenges in the US from the perspective of treating centers. Design, Setting, and Participants:This survey study was conducted from February to March 2025 among US member institutions of the Children's Oncology Group (COG) across 44 states. Exposure:Institutional characteristics, including participation in the National Cancer Institute Community Oncology Research Program (NCORP), US census region, site-reported annual pediatric ALL patient volume, and prior blinatumomab experience, were assessed. Main Outcomes and Measures:Incorporation of blinatumomab as standard therapy by pediatric B-ALL subtype; major outpatient care-delivery challenges defined as 4 or 5 on a 5-point Likert scale by more than 25% of centers. Results:Of 195 active US COG member institutions, 147 centers completed the survey and were successfully matched with a unique COG identifier, among which 35 institutions (23.8%) were NCORP participants. There were 32 institutions (21.8%) in Midwest, 30 institutions (20.4%) in Northeast, 60 institutions (40.8%) in South, and 25 institutions (17.0%) in West census regions. Most centers reported using blinatumomab as their institutional standard therapy for National Cancer Institute standard risk-average (134 centers [91.2%]), standard risk-high (144 centers [98.0%]), and high-risk (140 centers [95.2%]) B-ALL. Fewer centers reported using blinatumomab for infant (83 centers [56.5%]) or Philadelphia chromosome-positive (96 centers [65.3%]) B-ALL. The most common major outpatient blinatumomab site care-delivery challenges included lack of home care companies (75 centers [51.0%]), family distance to treating center (41 centers [27.9%]), and insurance coverage for home care companies (37 centers [25.2%]). There were 67 sites (45.6%) that reported having no home care company options for any patients. Conclusions and Relevance:In this study, challenges associated with pediatric blinatumomab home care were highly prevalent, with broader implications for health system infrastructure availability. These data highlight a need to plan for clinical implementation strategies alongside the development and testing of novel therapies.
This cross-sectional study of state-level health data of US children examines the association of lead service lines and blood lead level exceedance rates in a 10-year period that included the Flint water crisis.
Importance:Mitigating the harmful effects of digitalization on youth mental health is essential. Objectives:To evaluate the effectiveness of cognitive behavioral therapy (CBT) compared with a media literacy-based intervention for gaming disorder and unspecified internet use disorder and to determine whether universal or indicated prevention yields stronger benefits. Design, Setting, and Participants:PROTECTconfirm was a randomized clinical trial conducted from July 1, 2020, to August 31, 2024, across 44 secondary schools in Baden-Württemberg, Germany, with 1-, 4-, and 12-month follow-up. All students were included in universal prevention analyses, whereas indicated prevention analyses included a subgroup of adolescents at high risk meeting 2 or more Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria for gaming disorder or unspecified internet use disorder at baseline. Interventions:Students were individually randomized within 90 classes to PROTECTtraining, a CBT-based program; or PROTECTinfo, a structurally parallel media literacy program. Both consisted of four 90-minute sessions delivered weekly during school hours by trained local prevention professionals under live supervision and adherence protocols. Main Outcomes and Measures:The primary outcome was gaming disorder symptom severity and unspecified internet use disorder symptom severity, assessed at 12 months with a modified version of the Video Game Dependency Scale. Secondary outcomes included internalizing, externalizing, and transdiagnostic symptoms. Primary and secondary outcomes were analyzed according to the intention-to-treat principle. Results:A total of 1793 students were randomized to PROTECTtraining (n = 896; mean [SD] age, 13.1 [1.5] years; 498 male students [56.1%]) or PROTECTinfo (n = 897; mean [SD] age, 13.1 [1.5] years; 484 male students [54.8%]). Participants in the subsample of 205 adolescents at high risk showed significantly lower 12-month severity of gaming disorder and unspecified internet use disorder symptoms with PROTECTtraining than with PROTECTinfo (mean [SD] Modified Video Game Dependency Scale score: 14.7 [9.7] vs 17.7 [10.3]; within-group Cohen d = -0.91 [95% CI, -1.10 to -0.72] vs Cohen d = -0.61 [95% CI, -0.80 to -0.42]; between-group Cohen d = -0.30 [95% CI, -0.55 to -0.05]), but not in the total sample (mean [SD] Modified Video Game Dependency Scale score: PROTECTtraining, 8.8 [8.3] vs PROTECTinfo, 9.4 [8.4]; within-group Cohen d = -0.11 [95% CI, -0.18 to -0.05] vs Cohen d = -0.04 [95% CI, -0.11 to 0.02]; between-group Cohen d = -0.07 [95% CI, -0.16 to 0.01]). Secondary outcomes did not differ significantly between groups. Conclusions and Relevance:In this randomized clinical trial of 1793 adolescents, the CBT-based intervention reduced gaming disorder symptoms and unspecified internet use disorder symptoms more effectively than the media literacy-based intervention among adolescents at high risk. These findings support the use of CBT-based approaches primarily within indicated, rather than universal, prevention. Trial Registration:German Clinical Trials Register (DRKS) trial registration: DRKS00033989.
Importance:Geographic disparities in cancer clinical trial access are well described in the US, but patterns in bladder cancer remain poorly defined. Objective:To evaluate bladder cancer trial availability across US counties and its associations with epidemiologic and socioeconomic factors. Design, Setting, and Participants:This cross-sectional study of completed, open, or active bladder cancer clinical trials from June 1, 2019, to June 1, 2025, on ClinicalTrials.gov used data on county-level incidence, mortality, and Social Vulnerability Index (SVI) obtained from the Centers for Disease Control and Prevention, the National Cancer Institute, and the Agency for Toxic Substances and Disease Registry and included interventional bladder cancer clinical trials of adults at 1 or more US sites. Data were analyzed from July 1, 2025, to October 20, 2025. Exposures:Epidemiologic and socioeconomic characteristics of bladder cancer clinical trials. Main Outcome and Measures:Trial availability was defined as 1 or more bladder cancer trial sites per county. Trial volume (number of unique trials per county) was modeled using a multivariable zero-inflated negative binomial regression and reported as incidence rate ratios. Associations between trial characteristics and location in highest vs lowest bladder cancer mortality quintile counties were assessed using a generalized linear mixed-effects logistic regression model. Results:The study identified 436 bladder cancer trials across 713 US counties. Of 3145 counties, 713 (22.7%) had 1 or more trial sites, and 2432 (77.3%) had none. Most trials were sponsored by pharmaceutical companies (211 [48.4%]) or academic institutions (170 [39%]). Most trials were drug focused (350 [80.2%]) and early phase (phase 1 or phase 2; 314 [72%]). Higher bladder cancer incidence was associated with higher trial rates (incidence rate ratio [IRR], 1.03; 95% CI, 1.003-1.06). A higher bladder cancer mortality rate was associated with lower trial rates (IRR, 0.80; 95% CI, 0.73-0.88). Compared with counties with a high SVI, trial rates were higher in counties with a lower-middle (IRR, 1.57; 95% CI, 1.18-2.08), middle-high (IRR, 1.60; 95% CI, 1.22-2.11), and low SVI (IRR, 2.53; 95% CI, 1.89-3.38). Of 7091 trial sites, 225 (3.2%) were located in counties in the highest quintile for bladder cancer mortality. Pharmaceutical company-sponsored trials were less likely than academic trials to be in counties with the highest mortality rate (odds ratio, 0.11; 95% CI, 0.04-0.29; P < .001), as were trials enrolling fewer than 100 participants compared with more than 100 participants (odds ratio, 0.20; 95% CI, 0.09-0.46; P < .001). Conclusions and Relevance:In this cross-sectional study of 436 bladder cancer clinical trials across US counties, most counties lacked trials, with geographic availability concentrated in counties with a high bladder cancer incidence and low social vulnerability. Expanding trial sites to counties with a high mortality rate or a high SVI may improve the geographic availability of bladder cancer clinical trials.
Importance:Previous studies suggest that children exposed to COVID-19 during pregnancy may have an increased risk of neurodevelopmental disorders. However, these studies had limited follow-up periods and primarily evaluated broad neurodevelopmental concerns. Objective:To examine whether exposure to maternal COVID-19 during pregnancy is associated with an increased risk of neurodevelopmental or neurological disorders among offspring. Design, Setting, and Participants:This cohort study was conducted between November 2025 and February 2026. The sample included all children born in Norway between March 1, 2020, and December 31, 2023, with 22 completed gestational weeks and a birth weight greater than 500 g. Data were obtained from national registries, including maternal background characteristics from Statistics Norway, birth characteristics from the Medical Birth Registry of Norway, prenatal exposure to COVID-19 from the Norwegian Surveillance System for Communicable Diseases, and neurodevelopmental and neurological disorders from the Norwegian Patient Registry. Exposure:Maternal COVID-19 during pregnancy, which was defined as a positive PCR result for SARS-CoV-2 infection between conception (date of birth minus the gestational duration in days) and the date of delivery. Main Outcomes and Measures:The 8 outcomes of interest were any neurodevelopmental disorders, pervasive neurodevelopmental disorders (autism), developmental speech or language disorders, developmental motor disorders, intellectual disorders, any neurological disorders, epilepsy, and sensory impairments. Diagnoses of neurodevelopmental disorders, neurological disorders, and sensory impairments were registered in the national patient registries. Risks were evaluated using Cox proportional hazards regression. Results:Among the 204 663 children (104 728 males [51.2%]) included in this study, 16 325 (8.0%) were exposed to maternal COVID-19 during pregnancy. Exposed children did not have increased risk of any neurodevelopmental disorders (adjusted hazard ratio [AHR], 0.97; 95% CI, 0.88-1.08), pervasive neurodevelopment disorders (AHR, 0.88; 95% CI, 0.67-1.15), developmental speech or language disorders (AHR 1.13; 95% CI, 0.80-1.59), developmental motor disorders (AHR, 0.83; 95% CI, 0.44-1.56), intellectual disorders (AHR, 1.19; 95% CI, 0.65-2.19), any neurological disorders (AHR, 0.97; 95% CI, 0.88-1.07), epilepsy (AHR, 1.14; 95% CI, 0.87-1.48), or sensory impairments (AHR, 1.09; 95% CI, 0.92-1.30). These findings were mostly robust across sensitivity analyses and did not vary according to trimester of exposure or the dominant circulating SARS-CoV-2 variant. The exception was an increased risk of speech or language disorders among exposed children, excluding children born after March 1, 2022 (AHR, 2.22; 95% CI, 1.44-3.41); this sensitivity analysis was performed to limit misclassification due to reduced availability of SARS-CoV-2 testing. Conclusions and Relevance:In this population-based cohort study, children exposed to maternal COVID-19 prenatally did not show an increased risk of neurodevelopmental disorders, aside from an increased risk of speech or language disorders among those exposed in the early phase of the pandemic. These findings should be replicated in other populations and settings.
Importance:Although fluoride exposure at high levels during the perinatal period has been associated with socioemotional problems among children, there is limited evidence regarding potential associations at lower levels of fluoride exposure, particularly in the US. Objective:To examine the association between prenatal exposure to public drinking water fluoride levels and children's socioemotional problems in a pooled US pediatric consortium. Design, Setting, and Participants:This cohort study used observational pregnancy cohort data from January 1, 2005, to December 31, 2019, on children aged 1.5 to 17 years from the Environmental Influences on Child Health Outcomes (ECHO) Cohort, which took place at 20 prenatal pediatric cohort sites across 34 US states. Statistical analysis was conducted from December 2024 to December 2025. Exposure:Area-level, time-weighted, mean fluoride concentrations in public water were estimated based on residential addresses during pregnancy. Main Outcomes and Measures:Children's socioemotional problems were assessed using caregiver reports of internalizing and externalizing problems via the Child Behavior Checklist. Generalized estimating equation models evaluated the adjusted mean difference in T scores (1) across the range of exposure values in cubic spline models, (2) per 500.0-µg/L higher fluoride level in linear models, (3) across quartiles of exposure, and (4) at the US Public Health Services recommended cutoff (≤700.0 µg/L; 3998 less than the cutoff). Results:The cohort comprised 5520 children (mean [SD] age, 5.8 [3.0] years; 2849 boys [51.6%]). The mean (SD) prenatal time-weighted water fluoride level was 407.9 (361.0) µg/L (range, <1.4-3272.5 µg/L). The adjusted mean difference in emotional and behavioral problem T scores per 500.0-μg/L higher exposure to prenatal public water fluoride was -0.15 (95% CI, -0.85 to 0.56) for internalizing problems and 0.06 (95% CI, -0.44 to 0.55) for externalizing problems, consistently showing no associations at the continuous level. However, some positive associations were observed only when using change point models for externalizing problems (adjusted mean difference, 1.59 [95% CI, 0.72-2.47] per 500.0-µg/L increase above the inflection point), and for some subgroups. Conclusions and Relevance:In this cohort study, prenatal exposure to fluoride levels in regulated public water was not associated with internalizing and externalizing problems among offspring. In change point models, positive associations were found for externalizing problems. The results contribute to growing evidence that could inform future policy decisions regarding fluoride in the US public water systems. Additional studies are needed to further investigate this association, especially examining other sources of fluoride that may have an association with children's emotional and behavioral problems.
Importance:Perioperative interruption of vitamin K antagonist (VKA) therapy in patients with mechanical heart valves (MHVs) is complex, and contemporary data to inform management are limited. Objectives:To describe perioperative anticoagulation management and to estimate 30-day risks of arterial thromboembolism (ATE) and bleeding after VKA interruption in adults with left-sided MHVs. Design, Setting, and Participants:This retrospective cohort study included consecutive adult patients (aged ≥18 years) with left-sided aortic, mitral, or dual MHVs undergoing planned invasive procedures requiring VKA interruption from January 1, 2016, to December 31, 2023, with 30-day follow-up. The study was conducted at the thrombosis clinic at The Ottawa Hospital in Ontario, Canada. Exposure:Planned invasive procedure requiring temporary interruption of VKA therapy. Main Outcomes and Measures:Primary outcomes were 30-day postoperative ATE and major bleeding. Secondary outcomes included clinically relevant nonmajor bleeding (CRNMB) and all-cause mortality. Major bleeding and CRNMB were defined according to the International Society on Thrombosis and Hemostasis. Results:The cohort included 373 patients (median [IQR] age, 67 [60-73] years; 217 [58.2%] male) contributing 613 interruptions. Therapeutic-dose bridging was used preoperatively in 516 interruptions (84.2%) and postoperatively in 193 (31.5%) (99 of 215 [46.0%] in mitral or dual MHV vs 94 of 398 [23.6%] in aortic MHV interruptions). Patients with mitral or dual (vs aortic) valve position and prior thromboembolism had higher estimated odds of receiving postoperative therapeutic-dose bridging (mitral or dual vs aortic: adjusted odds ratio [aOR], 2.90; 95% CI, 1.91-4.41; prior thromboembolism: aOR, 1.91; 95% CI, 1.05-3.46). Estimated 30-day risks of ATE and major bleeding were 1.5% (95% CI, 0.8%-2.8%) and 2.1% (95% CI, 1.2%-3.6%), respectively. Clinically relevant bleeding (composite of major bleeding and CRNMB) occurred in 3.9% (95% CI, 2.6%-5.8%) of interruptions. Three deaths occurred (0.5%; 95% CI, 0.2%-1.5%), 1 attributed to fatal ischemic stroke. Omission of postoperative bridging was associated with higher estimated ATE risk (4.9% vs 0.9%; subdistribution hazard ratio [sHR], 5.30; 95% CI, 1.45-19.40; P = .01); this finding was no longer statistically significant in landmark analysis (sHR, 3.26; 95% CI, 0.62-17.21). Conclusions and Relevance:In this retrospective cohort study, patients with MHVs experienced clinically meaningful risks of perioperative ATE and bleeding. These data do not establish a causal protective effect of postoperative bridging. However, omitting bridging in patients with MHVs was associated with a higher estimated risk of ATE in exploratory analyses and should be approached cautiously, pending stronger evidence from representative cohorts.
This cross-sectional study evaluates patient characteristics associated with uptake of genetic testing for breast cancer susceptibility genes within an ethnically and racially diverse patient population in Montreal, Quebec, Canada.
Importance:The net benefit of oral anticoagulants (OACs) in patients with atrial fibrillation (AF) and advanced chronic kidney disease (CKD) not receiving dialysis remains uncertain. Objective:To compare the estimated effectiveness and safety of apixaban compared with warfarin and no OAC use among patients with AF and advanced CKD not receiving dialysis. Design, Setting, and Participants:This retrospective cohort study used a 3-group target trial emulation framework and included patients from Medicare fee-for-service claims (January 1, 2013, to December 31, 2022) and the Optum deidentified Clinformatics Data Mart database (January 1, 2013, to February 28, 2025). Eligible participants had AF, CKD stage 4 or 5, no prior dialysis, and continuous medical and pharmacy coverage. Data analysis was conducted from February 2025 to June 2026. Exposures:Initiation of apixaban or warfarin vs no oral anticoagulation. Main Outcomes and Measures:Primary outcomes were hospitalization for major bleeding, ischemic stroke, and their composite. Propensity score matching weights were used to balance baseline characteristics, and weighted hazard ratios (HRs) and rate differences (RDs) per 1000 person-years (PYs) were estimated. Results:The study included 14 712 apixaban users (7954 female [54.1%]; mean [SD] age, 78.93 [7.35] years), 6335 warfarin users (3148 female [49.7%]; mean [SD] age, 77.47 [7.03] years), and 21 005 nonusers of OACs (10 797 female [51.4%]; mean [SD] age, 79.59 [7.49] years). Compared with nonusers, apixaban was associated with an increased rate of major bleeding (HR, 1.32 [95% CI, 1.11 to 1.58]; RD, 17.16 [95% CI, 2.45 to 31.87] per 1000 PYs) and a lower rate of ischemic stroke (HR, 0.46 [95% CI, 0.32 to 0.66]; RD, -12.67 [95% CI, -20.65 to -4.69] per 1000 PYs), but there was no association with the composite outcome (HR, 1.05 [95% CI, 0.89 to 1.22]; RD, 6.13 [95% CI, -10.61 to 22.87] per 1000 PYs). Warfarin users had a higher rate of major bleeding (HR, 2.44 [95% CI, 2.06 to 2.88]) and no significant diffrence in the rate of ischemic stroke (HR, 0.87 [95% CI, 0.61 to 1.22]), resulting in a higher rate of the composite outcome compared with nonuse (HR, 1.95 [95% CI, 1.69 to 2.26]). Compared with warfarin, apixaban was associated with lower risk of major bleeding (HR, 0.55 [95% CI, 0.46 to 0.65]) and ischemic stroke (HR, 0.50 [95% CI, 0.33 to 0.78]). Conclusions and Relevance:This study found that among patients with AF and advanced CKD not receiving dialysis, anticoagulation was associated with reduced risk of ischemic stroke, but increased risk of bleeding compared with nonuse, suggesting that the trade-off between ischemic stroke reduction and bleeding risk was more favorable for apixaban than for warfarin.
Importance As the population living with HIV in the US ages, state-level projections of the aging dynamics among people with diagnosed HIV (PWDH) will be needed to inform local planning and intervention efforts. Objective To explore how aging dynamics of PWDH in the US are expected to differ at the state level between 2025 and 2040. Design, Setting, and Participants This decision analytic model used a calibrated model of HIV transmission to project epidemic trajectories from 2025 to 2040 in 24 US states representing 86% of PWDH in the US. Main Outcomes and Measures Change in median age of PWDH, among those older than 13 years, was estimated from 2025 to 2040 for each state. Results Among the 24 states analyzed, projections showed that by 2040, the median age of adult PWDH will increase from a mean of 51 (95% credible interval [CrI], 51-52) years to 61 (95% CrI, 59-63) years, and 46% (95% CrI, 43%-48%) of adult PWDH will be older than 65 years. Substantial heterogeneities were found in age distributions by state. More populous and urban states with higher median ages of PWDH in 2025 were projected to experience even further aging of the population with diagnosed HIV in the coming 15 years. By contrast, more rural and less populous states had younger populations of PWDH that were not projected to age substantially over time. Conclusions and Relevance This decision analytic model found that although the overall population of PWDH in the US is projected to age substantially, these effects will unfold differently across states. In the coming years, health care systems will need to plan to adapt to changing state-level demographic patterns among PWDH.
