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.
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:Open science practices are essential for improving transparency, reproducibility, and trust in biomedical research. Journals play a critical role in promoting these practices through editorial policies, yet implementation and impact remain unclear. Objective:To evaluate the open science policies of leading medical journals and assess implementation and detectability of practices using automated tools. Design, Setting, and Participants:This cross-sectional study of journal policies and open science practices evaluated research articles published in 10 leading general medical journals from January 2020 to December 2023. Additionally, the diagnostic accuracy of automated tools was validated against manual extraction. Exposures:Journal policies regarding open science practices and article-level implementation of 13 core practices including registration, protocol sharing, and intention to share data. Main Outcomes and Measures:Journal policies were assessed using the Transparency and Openness Promotion guidelines (TOP2025). At the article level, 13 core open science practices were examined. Additionally, 9 validated automated tools were applied to detect these practices, and their performance was compared with manual extraction of articles. Results:Overall, 15 624 research articles published in 10 general medical journals were analyzed (validation subset, 312 articles: 103 randomized clinical trials [RCTs], 98 meta-analyses, and 111 with other designs). At the journal level, TOP2025 evaluation identified substantial heterogeneity in policies, primarily applied to clinical trials. At the article level, open science practices were more frequently implemented in RCTs than other designs: registration (RCTs: 99% [95% CI, 97%-100%]; meta-analyses: 69% [95% CI, 56%-79%]; other designs: 16% [95% CI, 9%-26%]), protocol sharing (RCTs: 96% [95% CI, 93%-98%]; meta-analyses: 67% [95% CI, 54%-78%]; other designs: 20% [95% CI, 12%-33%]), and intention to share data (RCTs: 79% [95% CI, 67%-87%]; meta-analyses: 65% [51%-77%]; other designs: 70% [95% CI, 57%-81%]). Automated tools showed variable performance (F1 scores, 0.06-1.00) and generally underestimated practices. Conclusions and Relevance:In this cross-sectional study of 15 624 articles in 10 leading medical journals, journal policies were only partially aligned with TOP2025, and article-level open science practices were more frequently reported for RCTs than for other designs, supporting the need for stronger journal policies.
Importance:Balanced transfusion is a cornerstone of modern hemorrhage resuscitation, yet national adoption patterns and hospital practice variation remain poorly characterized, particularly following increasing use of whole blood (WB). Objective:To evaluate trends, between-hospital variation, and patient and institutional factors associated with balanced component and WB transfusion in US trauma centers. Design, Setting, and Participants:This retrospective cohort study of adult trauma patients in hemorrhagic shock receiving blood transfusion within 4 hours of hospital arrival used data from the Trauma Quality Improvement Program (2018-2024). Multilevel mixed-effects logistic regression was used to evaluate patient and hospital characteristics associated with balanced component and WB use and quantify hospital-level variation. Exposure:Patient demographic and injury characteristics, hospital structural characteristics, and calendar year. Main Outcomes and Measures:The primary outcome was balanced component and WB use within 4 hours of arrival, defined by standardized ratios of plasma to red blood cells and platelet to red blood cells or receipt of WB. Temporal trends and facility variation were assessed using adjusted odds ratios (ORs), intraclass correlation coefficients, and median ORs. Results:The study included 71 997 patients treated at 650 trauma centers (197 [30.3%] American College of Surgeons-verified level I). The median (IQR) age was 36.0 (26.0-52.0) years, 54 889 patients (76.2%) were male, and 45 185 patients (62.8%) sustained blunt injury. Balanced component and WB transfusion increased from 12.4% (918 transfusions) in 2018 to 37.6% (4244 transfusions) in 2024 (adjusted OR, 5.33; 95% CI, 4.88-5.81), largely corresponding to increasing WB adoption after 2020, whereas component-based balanced transfusion remained relatively stable. Significant between-hospital variation persisted after adjustment. Hospital-level differences accounted for 24% of variation in balanced component and WB use (intraclass correlation coefficient, 0.24; 95% CI, 0.21-0.26). Male sex, helicopter transport, and treatment at larger hospitals were associated with higher odds of balanced component and WB use, whereas major hemorrhage control surgery and severe torso injuries were negatively associated, despite higher total transfusion volumes. Conclusions and Relevance:In this retrospective cohort study of trauma patients at risk of hemorrhagic shock, the use of balanced component and WB use increased from 2018 to 2024, reflecting increasing WB adoption. Substantial between-hospital variation persisted. These findings can inform evaluation of hospital-level variation and future implementation of balanced transfusion practices across trauma centers.
Importance:Previous research has found associations between abortion policies and infant health. Differing methods complicate understanding which abortion policies matter for infant health. Objective:To examine associations between multiple state-level abortion policies and infant health. Design, Setting, and Participants:This retrospective cohort study obtained birth certificate data and cohort-linked birth-infant death files and used logistic regression, adjusting for individual and state controls, state-year combination fixed effects, state-specific time trends, and standard errors clustered by state, with sensitivity analyses to identify robust findings. Participants included liveborn singleton births in the US from 2005 to 2022. Data were analyzed from January 2025, to June 7, 2026. Exposures:Eleven abortion policies. Main Outcomes and Measures:The primary outcomes were low birth weight (<2500 g), preterm birth (<37 weeks), low Apgar score (<7), and infant death. Results:Among 64 789 079 births, the mean (SD) maternal age was 28.2 (6.0) years; 6.5% (n = 4 193 951) of neonates were low birth weight, 10.3% (n = 6 664 535) were preterm, 1.8% (n = 1 142 835) had a low Apgar score, and 0.53% (n = 341 399) died; 1.6% (n = 1 006 123) of mothers had no prenatal care, and 23.6% (n = 14 449 109) had late prenatal care. Waiting periods (adjusted odds ratio [aOR], 0.97 [95% CI, 0.96-0.99]) and medication abortion in-person requirements (aOR, 0.98 [95% CI, 0.97-0.99]) were associated with decreased low birth weight. For clinician-type qualifications, ambiguity regarding advanced practice clinician provision was associated with decreased infant deaths (aOR, 0.69 [95% CI, 0.58-0.83]), physician-only requirements were associated with increased low birth weight (aOR, 1.03 [95% CI, 1.01-1.05]) and preterm birth (aOR, 1.05 [95% CI, 1.02-1.07]), and advance practice clinician provision of medication abortion only was associated with increased low birth weight (aOR, 1.03 [95% CI, 1.01-1.05]). The 6-week, fetal heartbeat bans were associated with increased preterm births (aOR, 1.04 [95% CI, 1.00-1.07]); the 20-week, fetal pain bans were associated with increased low Apgar score (aOR, 1.21 [95% CI, 1.06-1.38]); ultrasonography information requirements were associated with increased low Apgar scores (aOR, 1.12 [95% CI, 1.02-1.24]); private insurance bans were associated with increased preterm births (aOR, 1.04 [95% CI, 1.01-1.07]); and hospital transfer agreement requirements were associated with increased low birth weight (aOR, 1.02 [95% CI, 1.00-1.03]) and increased preterm births (aOR, 1.02 [95% CI, 1.00-1.03]). Conclusions and Relevance:In this cohort study of US births, 5 abortion policies were associated with multiple increased adverse infant health outcomes, whereas 2 were associated with decreased low birth weight. Findings suggest multiple types of abortion policies-and not only total abortion bans-are relevant for infant health.
Importance:Opioids remain central to management of acute and chronic pain in sickle cell disease (SCD). Opioid dispensing declined over the 2010s amid opioid stewardship efforts, but patterns since 2020 are less clear. Analyses aggregating opioids into morphine milligram equivalents (MME) may obscure agent-specific patterns. Objective:To characterize opioid dispensing volume and per-recipient frequency, duration, and dose among individuals with SCD. Design, Setting, and Participants:A retrospective cohort study of commercially insured and Medicaid-enrolled patients with SCD using the Merative MarketScan databases across 3 periods from January 2011 to February 2016, March 2016 to December 2020, and January 2021 to December 2023. Exposure:Calendar time across 3 prespecified periods: January 2011 to February 2016, March 2016 to December 2020, and January 2021 to December 2023. Main Outcomes and Measures:Changes in opioid dispensing were examined across 3 periods (January 2011 to February 2016, March 2016 to December 2020, and January 2021 to December 2023). Segmented regression models estimated monthly percentage changes (MPCs) in 4 outcomes: (1) total dispensed prescriptions per 100 enrollees; and, among enrollees receiving opioids, (2) mean prescriptions per person, (3) mean days supplied, and (4) mean daily MMEs. Analyses included 6 opioids (hydromorphone, hydrocodone, morphine, tramadol, oxycodone, methadone) stratified by insurance type (commercial vs Medicaid). Results:Across 48 760 individuals with SCD contributing person-time, 24 692 (50.6%) were Medicaid beneficiaries, 20 969 (43.0%) were aged 19 to 40 years, and 29 380 (60.3%) were female. From January 2021 through December 2023, total dispensing increased for all 6 agents among Medicaid beneficiaries, with the largest monthly increases for methadone (MPC, 1.76%; 95% CI, 1.24% to 2.29%) and hydromorphone (MPC, 1.43%; 95% CI, 1.00% to 1.86%). Among commercial enrollees, total dispensing increased for oxycodone (MPC, 0.84%; 95% CI, 0.60% to 1.07%) and morphine (MPC, 0.87%; 95% CI, 0.42% to 1.33%), was stable for hydrocodone, hydromorphone, and methadone, and declined for tramadol (MPC, -0.79%; 95% CI, -1.16% to -0.42%). Dispensed prescriptions increased only for oxycodone among commercially insured individuals (MPC, 0.14%; 95% CI, 0.08% to 0.20%) and tramadol among those with Medicaid (MPC, 0.96%; 95% CI, 0.56% to 1.36%). Mean days supplied and mean daily MMEs did not significantly increase for any opioid-insurance combination. Conclusions and Relevance:Among individuals with SCD, total opioid dispensing increased or stabilized during 2021 to 2023 after prior declines, most prominently among Medicaid beneficiaries, without broad increases in per-recipient frequency, duration, or dose. These patterns are consistent with broader distribution of opioid dispensing rather than treatment intensification among recipients.
Importance:Stimulant-involved deaths continue to increase in the US, and methamphetamine use remains a weighty public health concern. Treating methamphetamine use disorders is complicated. Contingency management has demonstrated the best effectiveness but is not widely implemented. Objective:To examine the effectiveness of dedicated care navigation in linking patients to treatment. Design, Setting, and Participants:This prospective randomized clinical trial was conducted at an integrated safety-net health system in Denver, Colorado, between April 10, 2023, and December 31, 2024. Eligible participants were 18 years or older who had a methamphetamine-related encounter in an acute care setting; those with involuntary treatment holds, substance treatment in past 90 days or actively seeking treatment, and inability to provide consent were excluded. Participants completed baseline, 30-day, and 90-day study visits. Intervention:Dedicated care navigation, incorporating contingency management principles, with a focus on addressing health-related social needs. Main Outcomes and Measures:Linkage to treatment within 30 and 90 days of enrollment defined as a composite measure of at least 1 of the following: electronic health record data indicating a visit at the health system's substance treatment clinic, a behavioral health encounter at an outpatient clinic, temporary residential treatment, or self-reported treatment on the 30- and/or 90-day follow-up survey. Results:Of 192 participants enrolled in the Beginning Early and Assertive Treatment for Methamphetamine Use trial, 156 (81.3%) were male, and the median age was 39 (IQR, 31-47) years. Most participants were unstably housed (163 [84.9%]), not currently employed (158 [82.3%]), and without regular access to a working phone (94 [49.0%]). Of the 96 participants randomized to the intervention, 60 (62.5%) engaged in 2 or more navigation sessions, 45 (46.9%) completed the 30-day study visit, and 47 (49.0%) completed the 90-day study visit compared with 44 (46.3%) and 37 (38.5%), respectively, of the 96 randomized to the control arm. No statistically significant differences in treatment linkage were observed at 30 days (24 participants [25.0%] in both arms; risk ratio, 1.00 [95% CI, 0.61-1.63]) or 90 days post enrollment, (32 [33.3%] in intervention vs 24 [25.0%] in control arms; risk ratio, 1.33 [95% CI, 0.85-2.09]). Conclusions and Relevance:In this randomized clinical trial, integrating principles of contingency management into the intervention may have increased engagement with a dedicated care navigator but did not increase likelihood of linkage to treatment for methamphetamine use disorder. Trial Registration:ClinicalTrials.gov Identifier: NCT06033365.
Importance:Intimate partner violence (IPV) against women is a persistent global public health concern with lasting impacts on the health of affected women and their children. Although previous studies suggest a potential link between IPV and mortality among children younger than 5 years (under-5 mortality [U5M]), the evidence remains inconclusive. Objective:To examine whether different forms of IPV are associated with under-5, infant, and neonatal mortality. Data Sources:Seven databases (MEDLINE, EMBASE, Global Health, PsycINFO, Scopus, Web of Science, and CINAHL) were searched from database inception to April 22, 2026. Study Selection:Studies were included if they examined the association between forms of IPV (any IPV or subtypes such as physical, sexual, emotional violence, or partner control behavior) and under-5, infant, and neonatal mortality. Two reviewers independently conducted study selection. Data Extraction and Synthesis:The Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline was followed. Risk of bias was assessed using the Risk of Bias in Non-randomized Studies of Exposures tool. Random-effects meta-analyses were conducted to estimate pooled odds ratios (ORs) and 95% CIs. Results:Twenty-eight studies comprising 684 065 participants were included in the systematic review, of which 25 were included in the meta-analyses. IPV was associated with higher odds of U5M (OR, 1.10; 95% CI, 1.05-1.16), infant mortality (OR, 1.32; 95% CI, 1.11-1.57), and neonatal mortality (OR, 1.36; 95% CI, 1.19-1.55). Physical IPV (OR, 1.37; 95% CI, 1.17-1.61), sexual IPV (OR, 1.70; 95% CI, 1.33-2.17), and emotional IPV (OR, 1.29; 95% CI, 1.07-1.56) were associated with higher odds of neonatal mortality. Physical IPV was also associated with higher odds of infant mortality (OR, 1.20; 95% CI, 1.01-1.44). No statistically significant associations were observed between IPV subtypes and U5M. Conclusions and Relevance:In this systematic review and meta-analysis, IPV against women was associated with higher odds of under-5, infant, and neonatal mortality. These findings suggest the importance of addressing IPV within child health strategies.
