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Tackling the Orexin Conundrum: An Optimized LC-MS/MS Method Demonstrates Accurate CSF Quantification and Absence in Peripheral Blood

Anal Chem. 2026 May 12. doi: 10.1021/acs.analchem.6c00454. Online ahead of print.

ABSTRACT

Cerebrospinal fluid (CSF) orexin-A is the gold-standard biomarker for narcolepsy type 1 (NT1), however, conventional radioimmunoassays (RIA) often suffer from cross-reactivity and overestimation, fueling long-standing conundrum regarding orexin detection in peripheral blood. In this study, we developed an ultrasensitive LC-MS/MS method (LLOQ = 0.1 pg/mL) incorporating a streamlined one-step protein precipitation protocol coupled with acid-shielding and cocktail-protection strategies to mitigate severe nonspecific adsorption and enzymatic degradation. Verification in paired CSF and blood samples from narcolepsy patients and controls revealed that orexin-B and peripheral orexins remain consistently below the detection limit (<0.1 pg/mL), proving that previously reported ng/mL levels in blood are analytical artifacts. Our LC-MS/MS approach resolved a 50-fold quantitative overestimation by RIA and significantly improved diagnostic resolution for narcolepsy type 2 (AUC = 0.73, P < 0.05) where RIA failed to achieve statistical significance (P = 0.297). This study establishes a high-specificity analytical framework as a practical reference standard for refined sleep disorder diagnostics and confirms that CSF orexin-A remains the currently the most reliable clinical biomarker.

PMID:42118575 | DOI:10.1021/acs.analchem.6c00454

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Diabetes and cancer incidence among adults in the Hispanic Community Health Study/Study of Latinos

Cancer. 2026 May 15;132(10):e70430. doi: 10.1002/cncr.70430.

ABSTRACT

BACKGROUND: Diabetes is associated with an increased risk of cancer; however, few epidemiological studies of diabetes and cancer risk have focused on Hispanic/Latino adults. This study examined the associations between three time-varying measures of diabetes and cancer incidence among participants from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

METHODS: HCHS/SOL is a multi-site prospective cohort study of 16,415 Hispanic/Latino adults. Time-varying diabetes measures (assessed at visit 1: 2008-2011 and visit 2: 2014-2017) included diabetes status (no diabetes, pre-diabetes, and diabetes), glycemic control (no diabetes, pre-diabetes, controlled diabetes [hemoglobin A1c (HbA1c) <7.0%], and uncontrolled diabetes [HbA1c ≥7.0%]), and insulin resistance (no diabetes, pre-diabetes + Homeostatic Model Assessment of Insulin Resistance [HOMA-IR] <3.0, pre-diabetes + HOMA-IR ≥3.0, diabetes + HOMA-IR <3.0, and diabetes + HOMA-IR ≥3.0). Incident cancers diagnosed from visit 1 through 2021 were identified through state cancer registry linkages; 715 cancers including 330 obesity-related cancers (ORCs) were diagnosed over a mean follow-up of 10.7 years. The authors used survey-weighted marginal structural Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for each time-varying diabetes measure and overall cancer and ORC risk, adjusting for demographic, social, and behavioral characteristics.

RESULTS: Time-varying pre-diabetes and diabetes (vs. no diabetes) status were associated with cancer HRs of 1.82 (95% CI, 1.27-2.61) and 2.49 (95% CI, 1.65-3.74), respectively. HRs were further elevated among those with diabetes + HbA1c ≥7.0% (HR, 3.12; 95% CI, 1.44-6.79) and those with diabetes + HOMA-IR ≥3.0 (HR, 2.78; 95% CI, 1.69-4.56). Associations were stronger for ORC risk; however, estimates were less precise.

CONCLUSION: Diabetes is associated with increased risk of cancer and ORC. Diabetes prevention and control may be additionally important for cancer prevention among Hispanic/Latino adults.

PMID:42118574 | DOI:10.1002/cncr.70430

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Public Expectations for Food and Drug Administration Approval of AI-Based Clinical Decision Support Tools: Quantitative Study

JMIR AI. 2026 May 12;5:e84315. doi: 10.2196/84315.

ABSTRACT

BACKGROUND: Regulation of artificial intelligence (AI) has been slow relative to the pace of its integration into health care. Several AI diagnostic tools for diabetic retinopathy (DR) have already received Food and Drug Administration (FDA) clearance, making it a timely and concrete example for exploring public perspectives on regulatory approval. The scope of FDA regulation of AI tools is being explored, and public attitudes about regulatory oversight should inform these discussions and are explored in this paper. Prior research suggests that comfort, trust, and political orientation shape views on government regulation and emerging technologies, potentially affecting support for oversight of AI in health care.

OBJECTIVE: This study assessed the perceived importance of FDA approval for AI-supported clinical decision support tools, with DR as the use case. We explored how comfort with AI tool developers, trust in data sharing, political affiliation, and demographic characteristics relate to the importance of FDA approval among US adults.

METHODS: A national survey was conducted in 2023 using the NORC AmeriSpeak Panel, a probability-based sample including 1787 respondents, with a subset of 982 participants answering questions about a use case describing an AI tool for identifying DR. Participants rated the importance of FDA approval for such tools on a 4-point Likert scale, with responses dichotomized between high and low perceived importance. Logistic regression models assessed associations between this outcome and predictors including comfort with AI tool developers, trust in data sharing, political affiliation, and demographic characteristics.

RESULTS: Among the 982 respondents presented with the DR use case, 658 (67%) indicated that FDA approval was “fairly” or “very” important. Statistically significant factors associated with the outcome (“It is important that the AI tool is approved by the FDA”) included higher comfort with using the tool (odds ratio [OR] 1.44, 95% CI 1.11-1.87; P=.006), comfort with developers from private companies (OR 1.38, 95% CI 1.09-1.76; P=.008), and hospitals (OR 1.60, 95% CI 1.25-2.05; P<.001). Trust in responsible data sharing (OR 1.25, 95% CI 1.05-1.5; P=.01) and higher education (OR 1.64, 95% CI 1.02-2.62; P=.04) also predicted higher support. Lean or strong Republicans (OR 0.43, 95%CI 0.3-0.6; P<.001) and Independents (OR 0.63, 95% CI 0.42-0.96; P=.03) were less likely to view FDA approval as important, as were Black (OR 0.50, 95% CI 0.34-0.77; P<.001) and Hispanic (OR 0.57, 95% CI 0.38-0.86; P=.007) respondents compared with White respondents.

CONCLUSIONS: This study offers insights into public attitudes regarding FDA oversight of AI-based clinical decision support tools. Findings highlight how comfort, trust, and lower confidence from marginalized communities and some political groups shape perceived importance of FDA approval, offering a point for broader applications in health care AI governance. These factors should be better considered as health systems work to ensure trustworthy implementation of new AI technologies.

PMID:42118568 | DOI:10.2196/84315

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Longitudinal Evaluation of Research Career Intentions Among US Medical Students

JAMA Netw Open. 2026 May 1;9(5):e2611430. doi: 10.1001/jamanetworkopen.2026.11430.

ABSTRACT

IMPORTANCE: The physician-scientist workforce has been in decline for decades, and the shortage of physician-scientists from racial and ethnic groups that are underrepresented in medicine (URiM) is particularly acute. Medical school is a key developmental period during which research career intentions (RCI) may change, yet little is known about RCI evolution during this period.

OBJECTIVE: To evaluate factors associated with RCI among first-year medical students, overall and by URiM status.

DESIGN, SETTING, AND PARTICIPANTS: This is a cross-sectional analysis of baseline data from the ongoing Longitudinal Evaluation of Research Career Intentions Among Medical Students Study. Participants were first-year medical students enrolled during the 2024 to 2025 academic year at US medical schools accredited by the Liaison Committee on Medical Education. MD-PhD students were excluded.

EXPOSURES: The baseline survey collected information on sociodemographic factors, pre-medical school and first-year research experiences (eg, research education, research participation, mentorship, and authorship), medical school learning environment, and psychosocial characteristics.

MAIN OUTCOMES AND MEASURES: The primary outcome was RCI in year 1 of medical school, defined as intending to be significantly or exclusively involved in research during one’s medical career. Characteristics associated with RCI were evaluated using stability selection.

RESULTS: Among 1136 first-year medical student respondents (mean [SD] age, 24.7 [2.7] years; 790 female [69.5%]) at 134 US medical schools, 26.9% (306 students) reported RCI, with a slightly higher prevalence among URiM students than non-URiM students (246 students [28.2%] vs 60 students [23.9%]; standardized mean difference, 0.097). Prematriculation factors associated with RCI among all students included research participation (odds ratio [OR], 1.51; 95% CI, 1.13-2.00), conference presentation (OR, 1.56; 95% CI, 1.16-2.09), and manuscript authorship (OR, 1.38; 95% CI, 1.03-1.86). Postmatriculation factors included research participation (OR, 1.74; 95% CI, 1.31-2.30) and having a physician-scientist role model (OR, 1.72; 95% CI, 1.31-2.30). Factors uniquely associated with RCI among URiM students included prematriculation research experiences (OR, 1.51; 95% CI, 1.14-2.01) and presentation of research (OR, 1.57; 95% CI, 1.17-2.11) and postmatriculation manuscript authorship (OR, 1.84; 95% CI, 1.04-3.25). Among non-URiM students, only postmatriculation factors were uniquely associated with RCI, including having a research mentor (OR, 1.76; 95% CI, 1.34-2.31) and receiving education about physician-scientist work-life balance (OR, 1.63; 95% CI, 1.24-2.15).

CONCLUSIONS AND RELEVANCE: This cross-sectional analysis of baseline data from an ongoing cohort study found that RCI was prevalent among first-year medical students and was associated with characteristics and experiences prior to matriculation and during year 1. Some factors associated with RCI differed between URiM and non-URiM medical students, suggesting distinct pipelines to research career development. These findings highlight opportunities to support physician-scientist training through tailored education, exposure, and mentorship.

PMID:42118538 | DOI:10.1001/jamanetworkopen.2026.11430

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Projected Oral Health Outcomes and Costs Associated With Pediatric Medicaid Disenrollment

JAMA Netw Open. 2026 May 1;9(5):e2611457. doi: 10.1001/jamanetworkopen.2026.11457.

ABSTRACT

IMPORTANCE: Medicaid provides comprehensive dental coverage to more than 37 million children in the US and plays a central role in reducing barriers to care and improving oral health outcomes. Under the 2025 One Big Beautiful Bill Act (OBBBA), many of these children may be at risk of losing their Medicaid coverage.

OBJECTIVE: To estimate changes in oral health outcomes and health care costs associated with projected Medicaid coverage loss among US children.

DESIGN, SETTING, AND PARTICIPANTS: A stochastic decision-analytic microsimulation model was developed to project changes in oral health and economic outcomes associated with Medicaid coverage loss among US children aged 0 to 18 years over a 10-year horizon (2025-2034). Simulated population characteristics were informed by the nationally representative National Health and Nutrition Examination Survey (NHANES) 2013-2018. Sensitivity analyses evaluated uncertainty in policy magnitude and structural assumptions. All analyses were performed from July 25 to March 2, 2025.

EXPOSURE: Projected annual Medicaid disenrollment of 480 000 children under the 2025 OBBBA from 2025 through 2034.

MAIN OUTCOMES AND MEASURES: Incremental incident caries events and emergency department visits for nontraumatic dental-related conditions, quality-adjusted life-years (QALYs), and health care costs.

RESULTS: The simulated cohort was based on 11 696 NHANES participants aged younger than 19 years (mean [SD] age, 9.2 [0.1] years; 5778 [weighted percentage, 49.2%] females). Over 10 years, projected coverage loss was associated with 95 799 (95% uncertainty interval [UI], 15 107-171 514) additional incident caries events, 27 084 (95% UI, -41 015 to -12 458) QALYs lost, and $86.5 million (95% UI, $47.1-$125.1 million) in additional health care costs in the base-case scenario. Across alternative policy impact scenarios, incremental caries events ranged from 54 051 (95% UI, -5354 to 111 084) to 161 231 (95% UI, 58 630-261 271), and incremental costs ranged from $47.9 million (95% UI, $17.1-$77.6 million) to $145.8 million (95% UI, $92.5-$193.4 million).

CONCLUSIONS AND RELEVANCE: In this decision-analytic microsimulation modeling study, projected pediatric Medicaid coverage loss was associated with worsening oral health outcomes and increased health care costs. The magnitude of impact varied with the scale of coverage loss but remained adverse across alternative policy scenarios.

PMID:42118537 | DOI:10.1001/jamanetworkopen.2026.11457

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Risk-Stratified Transitional Care and Cardiovascular Hospitalizations by Sex: A Secondary Analysis of a Randomized Clinical Trial

JAMA Netw Open. 2026 May 1;9(5):e2611892. doi: 10.1001/jamanetworkopen.2026.11892.

ABSTRACT

IMPORTANCE: Female patients with heart failure (HF) are older and more often present with preserved left ventricular ejection fraction (LVEF), whereas male patients present with more ischemic disease. Despite these differences, an emergency department-based acute HF strategy may be equally applicable to both sexes.

OBJECTIVE: To determine whether the strategy for acute HF management in the Comparison of Outcomes and Access to Care for Heart Failure (COACH) trial differed by sex.

DESIGN, SETTING, AND PARTICIPANTS: This prespecified secondary analysis of the multicenter COACH stepped-wedge, cluster-randomized clinical trial included 10 acute care hospitals in Ontario, Canada. Data were collected from January 15, 2017, to January 15, 2019. Participants included patients presenting to a study emergency department with acute HF. Cox proportional hazards regression with interactions was used to evaluate whether intervention effects differed for females and males and to estimate sex-specific association with treatment. Data were analyzed from July 2024 to May 2025.

INTERVENTION: Risk stratification for disposition decisions from the emergency department and risk-guided postdischarge transitional care, examining sex interactions.

MAIN OUTCOMES AND MEASURES: Composite of death or cardiovascular hospitalizations at 30 days (primary outcome) and during extended follow-up to 20 months (co-primary outcome).

RESULTS: A total of 5452 patients were included in the analysis (median age, 78.0 [IQR, 68.0-85.0] years). The 2461 females were older (median age, 80.0 [IQR, 71.0-87.0] years) than the 2991 males (median age, 76.0 [IQR, 66.0-84.0] years). Females had more preserved LVEF (≥50%) compared with males (1107 [45.0%] vs 885 [29.6%]; standardized mean difference, 0.32). Males had more prior myocardial infarction compared with females (565 [18.9%] vs 338 [13.7%]; standardized mean difference, 0.14). There was no interaction by sex at 30 days (hazard ratios [HRs] for primary outcome, 0.88 [95% CI, 0.68-1.14] for females and 0.88 [95% CI, 0.71-1.08] for males; P = .98 for interaction) or 20 months (HRs for co-primary outcome, 0.99 [95% CI, 0.90-1.09] in females and 0.92 [95% CI, 0.85-1.00] in males; P = .38 for interaction). There was a significant interaction by sex for 20-month HF readmissions (P = .01 for interaction), with adjusted HRs of 0.92 (95% CI, 0.72-1.19) in females and 0.71 (95% CI, 0.58-0.87) in males. There were no sex interactions for other outcomes at either time point.

CONCLUSIONS AND RELEVANCE: In this secondary analysis of a stepped-wedge, cluster-randomized clinical trial, risk stratification for emergency department-based decision-making for disposition decisions and rapid postdischarge transitional care was similarly beneficial in males and females, with comparable outcomes after accounting for multiplicity.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02674438.

PMID:42118536 | DOI:10.1001/jamanetworkopen.2026.11892

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Stage IV Breast Cancer Incidence and Survival, 2010-2021

JAMA Netw Open. 2026 May 1;9(5):e2612042. doi: 10.1001/jamanetworkopen.2026.12042.

ABSTRACT

IMPORTANCE: Trends in the incidence of de novo stage IV breast cancer in the general population and in the percentage with stage IV disease remain underreported.

OBJECTIVES: To evaluate the incidence, percentage, and survival of people with de novo stage IV breast cancer diagnosed from 2010 through 2021.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study used data from the Surveillance, Epidemiology, and End Results program to identify all individuals diagnosed with de novo invasive breast cancer between January 1, 2010, and December 31, 2021. No exclusion criteria were applied. Data analyses were conducted from January 2024 to June 2025.

MAIN OUTCOMES AND MEASURES: Age-adjusted incidence rates of breast cancer and annual percentage changes (APC) from 2010 through 2021 were calculated. Among the diagnosed breast cancers, the yearly percentage of stage IV disease was also calculated. Changes in overall survival (OS) were evaluated for patients with stage IV breast cancer using multivariable Cox proportional hazards regression models stratified by tumor subtype.

RESULTS: Of 761 471 breast cancer diagnoses (median [IQR] age at diagnosis, 60 [50-70] years; 99.2% female), 43 934 (5.8%) were stage IV. Stage IV incidence increased from 9.5 (95% CI, 9.2-9.9) cases per 100 000 females in 2010 to 11.2 (95% CI, 10.9-11.6) cases per 100 000 females in 2021, an APC of 1.2% (95% CI, 0.8%-1.6%). The incidence of stages I to III disease also increased, from 163.0 (95% CI, 161.6-164.4) cases per 100 000 females in 2010 to 177.4 (95% CI, 176.1-178.8) cases per 100 000 females in 2021. Stage IV incidence increased across all tumor subtypes, with an APC of 2.0% (95% CI, 1.5%-2.6%) for hormone receptor (HR)-positive/ERBB2-negative, 1.6% (95% CI, 0.2%-2.9%) for HR-positive/ERBB2-positive, 1.3% (95% CI, -0.1%-2.7%) for HR-negative/ERBB2-positive, and 2.7% (95% CI, 1.4%-4%) for triple-negative disease. Stage IV incidence increased statistically significantly across all age groups and numerically across all racial groups. Among males, there was a statistically significant increase in stage IV incidence, with an APC of 3.7% (95% CI, 1.0%-6.5%). The percentage of stage IV diagnoses increased statistically significantly from 2010 through 2021 in each tumor subtype: 4.4% to 95.4% for HR-positive/ERBB2-negative, 8.1% to 91.6% for HR-positive/ERBB2-positive, 10.4% to 89.4% for HR-negative/ERBB2-positive disease, and 6.7% to 92.9% for triple-negative breast cancer. For each successive year, OS among patients diagnosed with stage IV improved, with adjusted hazard ratios of 0.99 (95% CI, 0.98-0.99) for HR-positive/ERBB2-negative, 0.97 (95% CI, 0.95-0.99) for HR-positive/ERBB2-positive, and 0.97 (95% CI, 0.94-0.99) for HR-negative/ERBB2-positive; changes for triple-negative breast cancer were not statistically significant (AHR, 0.99 [95% CI, 0.97-1.01]; P = .33).

CONCLUSIONS AND RELEVANCE: In this cohort study of individuals with stage IV breast cancer, incidence increased significantly overall, across ages, and for both sexes from 2010 through 2021. The percentage of individuals with stage IV vs stages I to III diagnoses also increased. Although OS improved, research is warranted to determine factors contributing to increased incidence, including potential changes in natural history of breast cancer, disease screening, and incidence and mortality of other conditions.

PMID:42118535 | DOI:10.1001/jamanetworkopen.2026.12042

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Prenatal Azithromycin Exposure and Risk of Neurodevelopmental Disorders in Children

JAMA Netw Open. 2026 May 1;9(5):e2612051. doi: 10.1001/jamanetworkopen.2026.12051.

ABSTRACT

IMPORTANCE: Azithromycin is commonly used during pregnancy to treat bacterial infections, but its effects on neurodevelopmental disorders (NDDs) remain inconclusive.

OBJECTIVE: To evaluate the risk of NDDs in children prenatally exposed to azithromycin compared with those exposed to other antibiotics or with no antibiotic exposure during gestation.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data from an administrative health claims database (January 1, 2012, to October 31, 2024). The study evaluated a mother-infant cohort of mothers aged 12 to 55 years with a live birth between December 1, 2012, and December 31, 2023, who filled at least 1 prescription for an antibiotic or were unexposed to antibiotics during pregnancy. Mothers with antibiotic exposure within 90 days before pregnancy were excluded.

EXPOSURES: Propensity scores were used to match children exposed to azithromycin with those exposed to other antibiotics or no antibiotics during the entire, early, and late pregnancy periods.

MAIN OUTCOMES AND MEASURES: Cox proportional hazards regression models were applied to assess the incidence of NDDs, including attention-deficit/hyperactivity disorder, autism spectrum disorder, speech and language disorder (SLD), developmental coordination disorder, and behavioral disorders, during follow-up, in the azithromycin cohort compared with those exposed to other antibiotic classes or those with no antibiotic exposure.

RESULTS: Among 15 527 mother-infant dyads (mean [SD] maternal age, 32.4 [4.1] years) included in this study, 742 (4.8%) were exposed to azithromycin, 3079 (19.8%) were exposed to other antibiotics, and 11 706 (75.4%) remained unexposed to antibiotics during pregnancy. After a mean (SD) follow-up of 5.5 (3.0) years, late pregnancy azithromycin exposure was associated with a lower risk of SLD compared with those unexposed (adjusted hazard ratio [AHR], 0.61; 95% CI, 0.39-0.94) as well as a lower risk of overall NDDs (AHR, 0.69; 95% CI, 0.49-0.98) and SLD (AHR, 0.59; 95% CI, 0.39-0.91) compared with those exposed to other antibiotics.

CONCLUSIONS AND RELEVANCE: In this cohort study, late pregnancy azithromycin exposure was associated with a lower risk of NDDs, particularly SLDs. However, azithromycin prescribing during pregnancy should remain guided by clinical necessity and existing safety recommendations; further studies using larger and more diverse populations are warranted to confirm these findings.

PMID:42118534 | DOI:10.1001/jamanetworkopen.2026.12051

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Children’s Exposure to Recent Family Member Criminal Legal System Involvement

JAMA Netw Open. 2026 May 1;9(5):e2612183. doi: 10.1001/jamanetworkopen.2026.12183.

ABSTRACT

IMPORTANCE: The growth of the US criminal legal system has broad implications for individual and societal economic and social well-being. Although this system primarily targets adults, children may experience adverse consequences from the criminal legal contacts (CLCs) of their parents and other family members.

OBJECTIVE: To examine the prevalence of children’s family member CLCs within the past year and past 5 years and how prevalence varied across relationship type, child age, and cohort period.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study created 2 samples (a courts sample and an incarceration sample) using secure criminal legal system records from 24 states and US Census Bureau surveys and administrative data between January 1, 2000, and December 31, 2021. Children were linked to parents and other family members using birth records and household surveys, and then family members were linked to criminal legal system records. Data were analyzed between July 15, 2023, and March 1, 2025.

EXPOSURE: Family CLCs.

MAIN OUTCOMES AND MEASURES: Mean prevalence rates of family CLCs were estimated for 4 types of recent (prior year and prior 5 years) family CLCs, including charges, convictions, felony convictions, and postadjudication incarceration, across family relationship (parent vs overall), child age (0-17 years), and cohort period (2000-2021).

RESULTS: The final courts sample included 371 100 000 observations for family charges and convictions linked to 43 490 000 unique children (56.7% aged 0-9 years and 43.2% aged 10-17 years; 50.7% boys), and the incarceration sample included 784 200 000 observations linked to 76 610 000 unique children (58.0% aged 0-9 years and 41.9% aged 10-17 years; 50.7% boys). Between 2000 and 2021, 15.0% of children had a family member charged within the past 5 years. In addition, 11.6% of children experienced a family member’s conviction, 3.6% a family member’s felony conviction, and 1.4% a family member’s incarceration within the past 5 years. Parent CLCs constituted a substantial proportion of children’s family CLCs (73.0%-78.7%) across 5-year exposures, with 11.8% of children experiencing a parent’s CLC within the past 5 years. Overall prevalence varied little by age, although parent CLCs were somewhat higher in early childhood. Prevalence of family CLCs among children increased substantially between 2000 and 2019 from 6.6% to 19.6% for past-5-year family criminal charges.

CONCLUSIONS AND RELEVANCE: This cross-sectional study found pervasive and increasing rates of children experiencing family CLCs. Given the adverse consequences of family CLCs for children, these findings have profound implications for child and adolescent well-being and the professionals who work with them.

PMID:42118533 | DOI:10.1001/jamanetworkopen.2026.12183

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Firearm Storage in Households With Children

JAMA Netw Open. 2026 May 1;9(5):e2612191. doi: 10.1001/jamanetworkopen.2026.12191.

ABSTRACT

IMPORTANCE: Children who live in households with firearms are several times more likely to die by suicide and unintentional firearm injury, compared with those in homes without guns. This risk can be mitigated by locking and unloading all household firearms.

OBJECTIVE: To describe firearm storage practices in homes with children overall and by the age of the youngest child in the household, and to estimate the number of children living in homes with firearms that are loaded and unlocked.

DESIGN, SETTING, AND PARTICIPANTS: A probability-based national survey study was conducted between December 18 and December 25, 2024, in the US. Eligible participants were firearm owners living with children younger than 18 years. Survey weights were incorporated to account for nonresponse and to produce nationally representative estimates.

EXPOSURE: Whether a child younger than 13 years lives in the household.

MAIN OUTCOMES AND MEASURES: The outcome of interest was firearm storage practices in the child’s home, categorized as (1) at least 1 gun loaded and unlocked; (2) no guns loaded and unlocked, but at least 1 loaded and locked or unloaded and unlocked; and (3) all guns unloaded and locked.

RESULTS: A total of 879 respondents personally owned a gun, lived in a household with 1 or more children younger than 18 years, and provided full information about storage. Among these gun owners, 65.3% were aged 18 to 44 years, 63.8% were male, and 70.2% lived with children aged 0 to 12 years. An estimated 21.1% (95% CI, 18.3%-24.3%) reported at least 1 gun loaded and unlocked; 34.8% (95% CI, 31.4%-38.3%) that all firearms were unloaded and locked; and the remainder otherwise (ie, neither any guns loaded and unlocked, nor all locked and unloaded). Among gun-owning adults whose children were all aged 13 to 17 years, an estimated 26.1% (95% CI, 20.2%-33.0%) stored at least 1 firearm loaded and unlocked, compared with 17.1% (95% CI, 12.9%-22.2%) of those whose children were all younger than 13 years and 17.4% (95% CI, 11.6%-25.2%) of those with both adolescents and younger children. Extrapolating to the 2024 US population, an estimated 32.3 million children younger than 18 years lived in a household with firearms, of whom 6.7 million (95% CI, 5.7-7.5 million) lived in a household with at least 1 loaded and unlocked gun.

CONCLUSIONS AND RELEVANCE: In this survey study of adult firearm owners who lived in households with children younger than 18 years, more than 1 in 5 reported that at least 1 firearm in their household was both loaded and unlocked, a practice more common when all children in the household were teenagers. More effective approaches to motivating parents to make their firearms inaccessible to both their teenagers and their younger children are needed.

PMID:42118532 | DOI:10.1001/jamanetworkopen.2026.12191