Obesity affects approximately one in five U.S. adolescents. Although an increasing number of medications are approved for adolescent obesity as an adjunct to health behavior and lifestyle treatment, national data on the prevalence and correlates of obesity medication prescribing for adolescents are sparse. Ambulatory electronic medical record data were analyzed to assess trends in the proportion of U.S. adolescents aged 12-17 years with obesity (body mass index ≥95th percentile) who were prescribed Food and Drug Administration (FDA) -approved obesity medications during 2018-2023. Log-binomial models were used to estimate characteristics of adolescents associated with receiving an obesity medication prescription in 2023. The proportion of U.S. adolescents who were prescribed obesity medications increased substantially in 2023 (by approximately 300% compared with 2020), the year after FDA expanded its approval of two obesity medications to include adolescents and after publication of the 2023 American Academy of Pediatrics clinical practice guideline. Despite this substantial relative increase, 0.5% of adolescents with obesity were prescribed an obesity medication in 2023, with a majority (83%) of prescriptions received by adolescents with severe obesity. Semaglutide (Wegovy, indicated for persons aged ≥12 years with obesity), and phentermine or phentermine-topiramate were most commonly prescribed. Prescribing prevalence was higher among girls than among boys (adjusted prevalence ratio [aPR] = 2.05), among adolescents aged 15-17 years than among those aged 12-14 years (aPR = 2.24), and among those with severe (class 2 or class 3) obesity than among those with class 1 obesity (aPR = 4.03 and 12.78, respectively). Prescribing prevalence was lower among Black or African American adolescents than among White adolescents (aPR = 0.61). Continued monitoring of the use of these medications could help guide strategies to ensure that all adolescents with obesity have access to evidence-based obesity treatment, including medications and health behavior and lifestyle interventions.

BACKGROUND: Improvements in outcomes among children and adolescents diagnosed with cancer are attributable to many factors-including clinical trials such as those administered through the Children's Oncology Group (COG), as well as population-based resources like the National Childhood Cancer Registry (NCCR). The objective of this study was to link COG trial data with the NCCR to evaluate overall enrollment patterns. METHODS: Data were received from the NCCR and COG, which were linked using an array of variables and then compared to evaluate enrollment patterns in COG studies from 2007-2018. Multivariable logistic regression was used to identify characteristics associated with not being enrolled in a COG study. RESULTS: Among 134,696 NCCR cancer patients, 51,062 matched with COG study enrollees. There were several differences in demographic and clinical characteristics between those enrolled and not enrolled in COG studies. Enrollment was higher among children aged 0-4 years compared to adolescents aged 15-19 years (53.7% vs 20.1%). Differences by race/ethnicity were also observed; for example, those who identified as non-Hispanic White were more likely to be enrolled than those who identified as non-Hispanic Asian/Pacific Islander (38.8% vs 32.9%). In a multivariable logistic regression model, several characteristics were significantly associated with not being enrolled in a COG study, including age at diagnosis, year of diagnosis, race/ethnicity, and cancer type. CONCLUSION: Our results suggest that several groups are underrepresented in COG clinical trials. This information can help guide the prioritization of population groups for engagement in future studies.

In this 2017-2019 community-based cohort, 245 healthy children were followed from birth to age two years. 46 EV-D68 infections were detected by nasal swabs, all between 08/2018-11/2018, with no detections in other study periods. 46% of infections met ARI criteria, of which 33% were medically attended; none required hospitalization.

OBJECTIVES: Cruise ship settings can facilitate transmission of respiratory infections. In March 2020, a COVID-19 outbreak occurred on the Grand Princess cruise ship. We describe the public health response, including a large-scale US federal quarantine intended to limit spread to communities not yet affected by COVID-19. METHODS: All US residents and symptomatic people requiring hospitalization disembarked beginning on March 9 and were transported to designated US military bases for federal quarantine or to hospitals or alternate care sites for medical care. Foreign nationals remained on board (crew) or were repatriated (passengers). People under federal quarantine were monitored daily for symptoms and tested voluntarily for SARS-CoV-2 upon arrival, as tests became available, and if symptoms developed. RESULTS: Of 3582 travelers (passengers and crew) on board, 2013 (56%) went to military bases, 59 (2%) went to hospitals or alternate care sites, 419 (12%) were repatriated, and the remainder (crew) quarantined on board. Overall, 1144 travelers (32%) were tested for SARS-CoV-2; of those, 155 (14%) had a positive test result. Among 2013 US residents quarantined, 1054 (52%) were tested. Of those, 115 (11%) had a positive test result, 37 (32%) of whom were symptomatic at testing. Proportions tested across bases ranged from 28% to 89%; test positivity ranged from 10% to 16%. Of 31 travelers hospitalized, the median (IQR) stay was 4 (4-9) nights, and 9 (29%) travelers died of SARS-CoV-2 complications. CONCLUSIONS: The Grand Princess outbreak was the first confirmed COVID-19 outbreak on a cruise ship in US waters. Multiagency public health responses allowed for isolation and quarantine, potentially helping to slow transmission into US communities. Ensuring that cruise ships have plans for communicable disease control and mitigation helps protect passenger and crew well-being.

Mpox emerged on the global scale in 2022 and predominately affected gay, bisexual, and other men who have sex with men (GBMSM). Stigma related to mpox is a potential harm for individuals experiencing multiple levels of marginalization who may already be discriminated against in family, health care, and other social domains. To understand perceived mpox stigma among cisgender GBMSM in the United States, we conducted a study within the American Men's Internet Survey with 824 cisgender GBMSM >= 15 years from August 5 to 15, 2022. Perceived mpox stigma was most prevalent among non-Hispanic Black individuals (13.9%) compared to non-Hispanic White individuals (6.0%) and particularly among men aged 25-29 (15.1%) compared to men aged 40+ (5.6%). In adjusted logistic regression models, mpox stigma was significantly associated with knowing someone who tested for mpox (adjusted odds ratio (aOR) = 4.3 95% confidence interval, CI [2.1, 9.0]), knowing someone who was vaccinated for mpox (aOR = 2.1; 95% CI [1.2, 3.7]), or having an unexplained rash in the 3 months prior to survey completion (aOR = 3.6; 95% CI [1.9, 7.0]). These initial findings suggested people who were more connected to mpox-affected social networks and also those who had symptoms consistent with mpox were more likely to experience stigma. Taken together, these data suggest the potential harmful impact of mpox-related stigma by affecting those who would most benefit from services. Moreover, these data suggest the importance of real-time stigma measurement and mitigation for both rapidly emergent and chronic infectious diseases to improve equity, reduce fear and misinformation, and optimize the impact of public health responses. (PsycInfo Database Record (c) 2025 APA, all rights reserved) Impact Statement Stigma can have far-reaching consequences. It can exacerbate health disparities, influence social networks, and discourage individuals from seeking preventative health care, including vaccination. This study's findings highlight that, even if not widespread, stigma can concentrate in marginalized groups and drastically affect individuals' lives. By acknowledging and addressing stigma, public health agencies and providers can foster inclusivity, limit fear, promote trust in health care systems, and improve the overall health and resilience of communities. (PsycInfo Database Record (c) 2025 APA, all rights reserved)

This survey was conducted with the aim of determining the public health risk of Rocky Mountain spotted fever and murine typhus in the urban and peri-urban areas of El Paso, as well as other areas in Texas, southern New Mexico, and Ciudad Juarez, Mexico. The approach was to assess the diversity of tick and flea species, determine if the ticks and fleas were infected with Rickettsia rickettsii and Rickettsia typhi (R. typhi), respectively, and assess previous human infection with Rickettsia species. Ticks and fleas were collected from domestic and wild animals and tested using a nested polymerase chain reaction assay. Human plasma samples were also tested for antibodies using an indirect fluorescence assay. Among 203 fleas, including Pulex irritans, Echidnophaga gallinacea, and Ctenocephalides felis (C. felis), collected from wild and domestic small mammals, only one pool of four C. felis collected from a dog in the El Paso community was positive for Rickettsia felis. All 194 Rhipicephalus sanguineus ticks collected from stray and domestic dogs in the El Paso community, southern Doña Ana County, and Ciudad Juarez were negative for Rickettsia spp. In Travis County, Texas, a total of 207 ticks collected from white-tailed deer, including 196 Ixodes scapularis and 11 Dermacentor albipictus, were negative for Rickettsia spp. pathogens. Among 375 archived human plasma samples collected in the El Paso community, only two were positive for R. typhi antibodies. These preliminary findings suggested that tick- and flea-borne diseases were not a major health risk in the El Paso community or the other areas included in this survey.

PURPOSE: Research has shown that the prevalence of vision difficulty is higher among US adults with low income than among those with higher income. We aimed to examine the trends in income-related inequalities in vision difficulty and to identify the contributions of explanatory factors. DESIGN: A cross-sectional and trend study. METHODS: Our study estimated income-related inequalities in self-reported vision difficulty among US adults aged 18 years or older using data from the National Health Interview Survey (NHIS) during 1999-2018. The concentration index was used to measure income-related inequality in vision difficulty and was decomposed into contributing factors. We examined temporal changes in income-related vision difficulty inequalities and contributors to those changes from 1999 to 2018. RESULTS: We found that vision difficulty was concentrated among lower income groups and the degree of income-related inequality in vision difficulty widened between 1999 and 2018. Decomposition analysis revealed that poverty-to-income ratio and public health insurance coverage were important contributors to income-related inequalities in vision difficulty, with smaller contributions made by smoking, physical inactivity, and female sex. Among all variables, non-White race/ethnicity, lower physical activity, and poverty-to-income ratio were important factors explaining the change in income-related inequality in vision difficulty. CONCLUSION: Vision difficulty was more prevalent in low-income populations. Our study enhances the understanding of socioeconomic disparities in vision difficulty, which could inform how to best target the deployment of eye care resources to maximize the visual potential of the US population.

INTRODUCTION: Municipalities can improve access to food through transit planning. The primary objective of this study was to describe the prevalence of public transit supports for food access among a sample of US municipalities and their association with the municipalities' sociodemographic characteristics. METHODS: This study used a nationally representative sample (N = 1,956) of US municipalities with a population of at least 1,000 that responded to the 2021 National Survey of Community-Based Policy and Environmental Supports for Healthy Eating and Active Living. We assessed 4 outcomes: public transit availability and planning, presence of demand responsive transportation (DRT), DRT services to food retail destinations (farmers markets and supermarkets), and consideration of these locations in transit planning. We used χ(2) tests to compare the prevalence of outcomes by municipal characteristics and multivariable logistic regression to calculate odds ratios to assess the relationship between municipal characteristics and having DRT. RESULTS: Approximately half (weighted 53.2%) of municipalities reported having or planning for public transit, of which 27.1% and 52.6% reported considering service to farmers markets or supermarkets, respectively. Approximately one-third (35.5%) of municipalities reported having DRT, of which 52.0% and 84.4% reported services to farmers markets or supermarkets, respectively. All outcomes significantly differed by municipal characteristics. We found higher odds of having DRT in municipalities with 2,500 to 50,000 people or more (vs <2,500 people); those with 50% or less of the population being non-Hispanic White (vs >50% non-Hispanic White); and municipalities containing low-income/low-access tracts. The odds of having DRT were lower in rural (vs urban) municipalities and in those in Northeast and South (vs the Midwest). CONCLUSION: Results suggest opportunities for municipalities to use transit planning to improve food access, especially in northeastern, southern, smaller, or rural communities.

Background: A contemporary description and estimates for rates of chronic kidney disease (CKD) in type 1 diabetes are needed to inform risk reduction strategies. The study aim was to assess prevalence and severity of CKD based on a population with type 1 diabetes receiving care at a large United States health system. Methods: Type 1 diabetes was identified through the Providence health system electronic health records during 2013–2022. Prevalent CKD was defined cross-sectionally by ≥ 90-day persistence of estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, urine albumin-to-creatinine ratio ≥30 mg/g, or urine protein-to-creatinine ratio ≥0.15 g/g. Multivariable logistic regression models analyzed variable associations with CKD and severe kidney disease (eGFR < 45 mL/min/1.73 m2, dialysis, or transplant). Findings: The study population (N = 23,589) was 48.6% female with a mean ± SD age of 38 ± 17 years. CKD prevalence was 27.1%. Higher odds of CKD were found for females (odds ratio: 1.36 [95% confidence interval]: 1.26–1.47); age 60–79 years (reference 12–17 years; 2.22 [1.83–2.69]); Asian (reference White; 1.71 [1.20–2.44]), Black or African American (1.76 [1.45–2.14]), and Other race (1.33 [1.04–1.71]) populations. CKD odds were higher with hypertension, heart failure, and atherosclerotic cardiovascular disease. Severe kidney disease was present in 10.8% with higher odds among Black or African American (2.08 [1.23–3.54]) and Native Hawaiian or Pacific Islander (2.62 [1.28–5.38]) populations. Interpretation: CKD was present in nearly one of three persons with type 1 diabetes with higher risks for females, older adults, racial and ethnic minorities, and those with cardiovascular diseases. Severe kidney disease was found in over one-tenth and more likely in Black or African American and Native Hawaiian or Pacific Islander populations. Focus on disproportionately affected groups who may benefit from monitoring and interventions to improve clinical outcomes will be important for public health and health system strategies to reduce risks of CKD and severe kidney disease in type 1 diabetes. Funding: This work was supported in part by CDC project numbers 75D301-21-P-12254 and 75D301-23-C-18264, and in part by Brigham Research Institute. © 2025 The Author(s)

Lampreys use variable lymphocyte receptors (VLR) comprising leucine-rich-repeat (LRR) segments for antigen recognition, distinct from immunoglobulin-based receptors of jawed vertebrates. Lamprey VLRs are as diverse and antigen-specific as immunoglobulin-based antibodies, with unique advantages including high avidity, pH stability, and recognition of novel antigen epitopes. Here we describe the generation of VLR monoclonal antibody against histidine rich protein-2 (HRP-2) of Plasmodium falciparum, a causative agent of malaria. HRP-2, expressed by all parasite stages and secreted into plasma, serves as an effective biomarker of infection. Lamprey larvae immunized with purified HRP-2 protein produced specific VLRB antibodies with relatively high serum titers. Using white blood cells from immunized lampreys, we constructed VLR cDNA libraries expressed on yeast surface. Through yeast display screening, we selected recombinant VLRB antibody 5A10 with high affinity and specificity for HRP-2, recognizing both recombinant and native proteins from P. falciparum culture supernatants and infected patient samples. The antibody retains its binding capacity at temperatures up to 70 °C, significantly outperforming a commercial mouse IgG-based anti-HRP-2 antibody. This HRP-2-specific VLR antibody shows promise for improved malaria diagnostics, particularly in tropical regions requiring heat-stable tests.

PURPOSE: To estimate the number of screenings received, life-years (LYs) saved, and number of screenings per LY saved per woman who participated in the National Breast and Cervical Cancer Early Detection Program (NBCCEDP) (Program) compared with those who did not participate (no Program). METHODS: We developed a time-to-event simulation model to compare the outcomes of women participating in the Program vs. no Program, categorized by race/ethnicity. Model input parameters included data from the Program's minimum data elements, United States Cancer Statistics, National Health Interview Survey, and published literature. The Program's impact was calculated as the difference in LYs between the Program and no Program using data from 2010 to 2019. RESULTS: Among 1 million women of all races/ethnicities who participated in the NBCCEDP in the last 10 years, 457,152 (standard deviation [SD]: 848) received more screenings than those who did not participate. These participants saved an average of 0.027 LYs per woman screened. In addition, we estimated that about 17 screenings would be required to save an additional 1 LY per woman screened in the Program compared with no Program. Per woman screened by race/ethnicity, non-Hispanic Black women had the highest estimated 0.075 LYs saved, followed by Hispanic women with 0.025 LYs, non-Hispanic White with 0.014 LYs, and non-Hispanic American Indian/Alaska Native and Asian/Pacific Islander had the least health outcome with 0.011 LYs. CONCLUSION: The reported findings underscore the importance of providing preventive health services to populations that might not otherwise have access to these services.

Racial misclassification on death certificates leads to inaccurate mortality data for American Indian and Alaska Native (AI/AN) populations. We describe methods for correcting for racial misclassification among non-Hispanic AI/AN (NH-AI/AN) populations using data from the year 2020. We linked National Death Index (NDI) records with the Indian Health Service (IHS) patient registration database to identify AI/AN decedents. Matches were then linked to the National Vital Statistics System (NVSS) mortality data to identify AI/AN individuals that had been misclassified as another race on their death certificates. Analyses were limited to NH-AI/AN and purchased/referred care delivery areas (PRCDA) or urban areas. We compared death rates and counts pre- and post- linkage and calculated sensitivity and classification ratios by region, sex, age, cause of death (COD) and urban area. Racial misclassification on death certificates among NH-AI/AN varied by geographic region. Some of the highest racial misclassification occurred in the Southern Plains and Pacific Coast. Death rates for NH-AI/AN people and differences between NH-AI/AN and Non-Hispanic White (NHW) people were larger using the linked data. Improving AI/AN mortality data using linkages between vital statistics data and IHS strengthens data quality and can help address health disparities through public health planning efforts.

IMPORTANCE: The oral microbiome likely plays key roles in human health. Yet, population-representative characterizations are lacking. OBJECTIVE: To characterize the composition, diversity, and correlates of the oral microbiome in US adults. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed data from the population-representative National Health and Nutrition Examination Survey (NHANES) from 2009 to 2012. Microbiome data were made publicly available in 2024. NHANES participants were aged 18 to 69 years and provided oral rinse samples in 1 of 2 consecutive NHANES cycles (2009-2010 and 2011-2012). EXPOSURES: Demographic, socioeconomic, behavioral, anthropometric, metabolic, and clinical characteristics. MAIN OUTCOMES AND MEASURES: Oral microbiome measures, characterized through 16S ribosomal RNA gene sequencing, included α diversity (observed amplicon sequence variants [ASVs], Faith phylogenetic diversity, Shannon-Weiner Index, and Simpson Index); β diversity (unweighted UniFrac, weighted UniFrac, and Bray-Curtis dissimilarity); and prevalence and relative abundance at phylum level through genus level. Analyses accounted for the NHANES complex sample design. RESULTS: This study included 8237 US adults aged 18 to 69 years, representing 202 314 000 individuals (102 813 000 men [50.8%]; mean [SD] age, 42.3 [14.4] years; 9.3% self-reported as Mexican American, 12.1% as non-Hispanic Black, 64.7% as non-Hispanic White, 5.9% as other Hispanic, and 8.1% as other non-Hispanic individuals). The oral microbiome encompassed 37 bacterial phyla, 99 classes, 212 orders, 446 families, and 1219 genera. Five phyla (Firmicutes, Actinobacteria, Bacteroidetes, Proteobacteria, and Fusobacteria) and 6 genera (Veillonella, Streptococcus, Prevotella 7, Rothia, Actinomyces, and Gemella) were present in nearly all US adults (weighted prevalence, >99%). These genera were the most abundant, accounting for 65.7% of total abundance. Observed ASVs showed a quadratic pattern with age (peak at 30 years), were similar by sex, significantly lower among non-Hispanic White individuals, and increased with greater body mass index (BMI), alcohol use, and periodontal disease severity. All covariates together accounted for a modest proportion of oral microbiome variability as measured by β diversity: R2 = 8.7% (95% CI, 8.4%-9.1%) for unweighted UniFrac, R2 = 7.2% (95% CI, 6.6%-7.7%) for weighted UniFrac, and R2 = 6.3% (95% CI, 3.1%-6.7%) for Bray-Curtis matrices. By contrast, relative abundance of a few genera explained a high percentage of variability in β diversity for weighted UniFrac: Aggregatibacter (R2 = 22.4%; 95% CI, 22.1%-22.8%), Lactococcus (R2 = 21.6%; 95% CI, 20.9%-22.3%), and Haemophilus (R2 = 18.4%; 95% CI, 18.1%-18.8%). Prevalence and relative abundance of numerous genera were associated with age, race and ethnicity, smoking, BMI categories, alcohol use, and periodontal disease severity. CONCLUSIONS AND RELEVANCE: This cross-sectional study of the oral microbiome in US adults showed that a few genera were universally present and a different set of genera explained a high percentage of oral microbiome diversity across the population. This comprehensive characterization provides a contemporary reference standard for future studies.

Objectives. To characterize the intersection of social determinants of health, measured as the availability of community opportunities for healthy living, and sexually transmitted infections (STIs) in California. Methods. Geocoded 2013-2021 California bacterial STI cases were aggregated into Healthy Places Index (HPI) quartiles. Communities in the lowest scoring HPI quartile have the fewest opportunities for healthy living, while communities in the highest scoring quartile have the most opportunities. Results. As community opportunities became more available, bacterial STI risk decreased. Asian people had the lowest bacterial STI rates, while Black/African American people had the highest. As community opportunities increased, White people had the largest overall STI risk reduction, Native Hawaiian and other Pacific Islander people had the smallest reduction, Hispanic/Latino people had equivalent gonorrhea and early syphilis risk, and American Indian/Alaska Native people had equivalent chlamydia risk. Conclusions. Although STI incidence decreased as community opportunities increased, people of different racial and ethnic identities were differentially affected. Because the availability of community opportunities is not enough to mitigate racial health disparities, more work is needed to ensure community-level STI prevention efforts are accessible and inclusive. (Am J Public Health. 2025;115(5):799-807. https://doi.org/10.2105/AJPH.2024.307963).

BACKGROUND: Split-hand/foot malformation (SHFM) is a rare, genetically heterogeneous, congenital limb defect. Some but not all associated genes are known; therefore, the aim was to identify genes underlying SHFM. METHODS: Buccal cell-derived DNA from 26 children with SHFM and their parents who participated in the National Birth Defects Prevention Study was exome sequenced. Family-based trio analyzes prioritized rare coding variants by inheritance patterns, predicted pathogenicity, and location within putative limb development genes. Copy-number variants in SHFM candidate genomic regions were also examined. Case-control analyzes compared coding variants between case children and 1191 controls (parents of children with non-limb birth defects). Variant validation was by Sanger sequencing or droplet digital polymerase chain reaction. RESULTS: In family-based analyzes, the prioritized and validated variants (each in a single family) included likely damaging variants that were heterozygous and de novo in speckle type BTB/POZ protein (SPOP) and ubiquitin-like modifier activating enzyme 2 (UBA2), X-linked recessive in fibroblast growth factor 13 (FGF13) and RNA binding motif protein 10 (RBM10), and compound heterozygous in interleukin enhancer binding factor 3 (ILF3). Validation assays did not confirm predicted de novo copy-number gains at chromosomes 10q24 and 19p13.11. Case-control analyzes did not identify statistically significant associations. CONCLUSION: Exome analysis nominated new susceptibility genes (FGF13, ILF3, RBM10, SPOP) and detected a variant in a known candidate gene (UBA2). Follow-up investigation is needed to ascertain damaging variants in these genes in additional cases with SHFM and evaluate the impact of the variants on gene expression, protein function, and limb development.

The protocol of a randomized trial is the foundation for study planning, conduct, reporting and external review. However, trial protocols vary in their completeness and often do not address key elements of design and conduct. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was first published in 2013 as guidance to improve the completeness of trial protocols. Periodic updates incorporating the latest evidence and best practices are needed to ensure that the guidance remains relevant to users. Here, we aimed to systematically update the SPIRIT recommendations for minimum items to address in the protocol of a randomized trial. We completed a scoping review and developed a project-specific database of empirical and theoretical evidence to generate a list of potential changes to the SPIRIT 2013 checklist. The list was enriched with recommendations provided by lead authors of existing SPIRIT/CONSORT (Consolidated Standards of Reporting Trials) extensions (Harms, Outcomes, Non-pharmacological Treatment) and other reporting guidelines (TIDieR). The potential modifications were rated in a three-round Delphi survey followed by a consensus meeting. Overall, 317 individuals participated in the Delphi consensus process and 30 experts attended the consensus meeting. The process led to the addition of two new protocol items, revision to five items, deletion/merger of five items, and integration of key items from other relevant reporting guidelines. Notable changes include a new open science section, additional emphasis on the assessment of harms and description of interventions and comparators, and a new item on how patients and the public will be involved in trial design, conduct and reporting. The updated SPIRIT 2025 statement consists of an evidence-based checklist of 34 minimum items to address in a trial protocol, along with a diagram illustrating the schedule of enrollment, interventions and assessments for trial participants. To facilitate implementation, we also developed an expanded version of the SPIRIT 2025 checklist and an accompanying explanation and elaboration document. Widespread endorsement and adherence to the updated SPIRIT 2025 statement have the potential to enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, funders, research ethics committees, journals, trial registries, policymakers, regulators and other reviewers.

IMPORTANCE: The protocol of a randomised trial is the foundation for study planning, conduct, reporting, and external review. However, trial protocols vary in their completeness and often do not address key elements of design and conduct. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was first published in 2013 as guidance to improve the completeness of trial protocols. Periodic updates incorporating the latest evidence and best practices are needed to ensure that the guidance remains relevant to users. OBJECTIVE: To systematically update the SPIRIT recommendations for minimum items to address in the protocol of a randomised trial. DESIGN: We completed a scoping review and developed a project specific database of empirical and theoretical evidence to generate a list of potential changes to the SPIRIT 2013 checklist. The list was enriched with recommendations provided by lead authors of existing SPIRIT/CONSORT (Consolidated Standards of Reporting Trials) extensions (Harms, Outcomes, Non-pharmacological Treatment) and other reporting guidelines (TIDieR). The potential modifications were rated in a three-round Delphi survey followed by a consensus meeting. FINDINGS: Overall, 317 individuals participated in the Delphi consensus process and 30 experts attended the consensus meeting. The process led to the addition of two new protocol items, revision to five items, deletion/merger of five items, and integration of key items from other relevant reporting guidelines. Notable changes include a new open science section, additional emphasis on the assessment of harms and description of interventions and comparators, and a new item on how patients and the public will be involved in trial design, conduct, and reporting. The updated SPIRIT 2025 statement consists of an evidence based checklist of 34 minimum items to address in a trial protocol, along with a diagram illustrating the schedule of enrolment, interventions, and assessments for trial participants. To facilitate implementation, we also developed an expanded version of the SPIRIT 2025 checklist and an accompanying explanation and elaboration document. CONCLUSIONS AND RELEVANCE: Widespread endorsement and adherence to the updated SPIRIT 2025 statement have the potential to enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, funders, research ethics committees, journals, trial registries, policymakers, regulators, and other reviewers.

IMPORTANCE: The protocol of a randomized trial is the foundation for study planning, conduct, reporting, and external review. However, trial protocols vary in their completeness and often do not address key elements of design and conduct. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was first published in 2013 as guidance to improve the completeness of trial protocols. Periodic updates incorporating the latest evidence and best practices are needed to ensure that the guidance remains relevant to users. Herein, we systematically update the SPIRIT recommendations for minimum items to address in the protocol of a randomized trial. OBSERVATIONS: We completed a scoping review and developed a project specific database of empirical and theoretical evidence to generate a list of potential changes to the SPIRIT 2013 checklist. The list was enriched with recommendations provided by lead authors of existing SPIRIT/CONSORT (Consolidated Standards of Reporting Trials) extensions (harms, outcomes, nonpharmacological treatment) and other reporting guidelines (Template for Intervention Description and Replication [TIDieR]). The potential modifications were rated in a 3-round Delphi survey followed by a consensus meeting. Overall, 317 individuals participated in the Delphi consensus process and 30 experts attended the consensus meeting. The process led to the addition of 2 new protocol items, revision to 5 items, deletion/merger of 5 items, and integration of key items from other relevant reporting guidelines. Notable changes include a new open-science section, additional emphasis on the assessment of harms and description of interventions and comparators, and a new item on how patients and the public will be involved in trial design, conduct, and reporting. The updated SPIRIT 2025 statement consists of an evidence based checklist of 34 minimum items to address in a trial protocol, along with a diagram illustrating the schedule of enrollment, interventions, and assessments for trial participants. To facilitate implementation, we also developed an expanded version of the SPIRIT 2025 checklist and an accompanying explanation and elaboration document. CONCLUSIONS AND RELEVANCE: Widespread endorsement and adherence to the updated SPIRIT 2025 statement have the potential to enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, funders, research ethics committees, journals, trial registries, policy makers, regulators, and other reviewers.

IMPORTANCE: The protocol of a randomised trial is the foundation for study planning, conduct, reporting, and external review. However, trial protocols vary in their completeness and often do not address key elements of design and conduct. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was first published in 2013 as guidance to improve the completeness of trial protocols. Periodic updates incorporating the latest evidence and best practices are needed to ensure that the guidance remains relevant to users. OBJECTIVE: To systematically update the SPIRIT recommendations for minimum items to address in the protocol of a randomised trial. DESIGN: We completed a scoping review and developed a project specific database of empirical and theoretical evidence to generate a list of potential changes to the SPIRIT 2013 checklist. The list was enriched with recommendations provided by lead authors of existing SPIRIT/CONSORT (Consolidated Standards of Reporting Trials) extensions (Harms, Outcomes, Non-pharmacological Treatment) and other reporting guidelines (TIDieR). The potential modifications were rated in a three-round Delphi survey followed by a consensus meeting. FINDINGS: Overall, 317 individuals participated in the Delphi consensus process and 30 experts attended the consensus meeting. The process led to the addition of two new protocol items, revision to five items, deletion/merger of five items, and integration of key items from other relevant reporting guidelines. Notable changes include a new open science section, additional emphasis on the assessment of harms and description of interventions and comparators, and a new item on how patients and the public will be involved in trial design, conduct, and reporting. The updated SPIRIT 2025 statement consists of an evidence-based checklist of 34 minimum items to address in a trial protocol, along with a diagram illustrating the schedule of enrolment, interventions, and assessments for trial participants. To facilitate implementation, we also developed an expanded version of the SPIRIT 2025 checklist and an accompanying explanation and elaboration document. CONCLUSIONS AND RELEVANCE: Widespread endorsement and adherence to the updated SPIRIT 2025 statement have the potential to enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, funders, research ethics committees, journals, trial registries, policymakers, regulators, and other reviewers.

BACKGROUND: Well designed and properly executed randomised trials are considered the most reliable evidence on the benefits of healthcare interventions. However, there is overwhelming evidence that the quality of reporting is not optimal. The CONSORT (Consolidated Standards of Reporting Trials) statement was designed to improve the quality of reporting and provides a minimum set of items to be included in a report of a randomised trial. CONSORT was first published in 1996, then updated in 2001 and 2010. Here, we present the updated CONSORT 2025 statement, which aims to account for recent methodological advancements and feedback from end users. METHODS: We conducted a scoping review of the literature and developed a project-specific database of empirical and theoretical evidence related to CONSORT, to generate a list of potential changes to the checklist. The list was enriched with recommendations provided by the lead authors of existing CONSORT extensions (Harms, Outcomes, Non-pharmacological Treatment), other related reporting guidelines (TIDieR) and recommendations from other sources (e.g., personal communications). The list of potential changes to the checklist was assessed in a large, international, online, three-round Delphi survey involving 317 participants and discussed at a two-day online expert consensus meeting of 30 invited international experts. RESULTS: We have made substantive changes to the CONSORT checklist. We added seven new checklist items, revised three items, deleted one item, and integrated several items from key CONSORT extensions. We also restructured the CONSORT checklist, with a new section on open science. The CONSORT 2025 statement consists of a 30-item checklist of essential items that should be included when reporting the results of a randomised trial and a diagram for documenting the flow of participants through the trial. To facilitate implementation of CONSORT 2025, we have also developed an expanded version of the CONSORT 2025 checklist, with bullet points eliciting critical elements of each item. CONCLUSIONS: Authors, editors, reviewers, and other potential users should use CONSORT 2025 when writing and evaluating manuscripts of randomised trials to ensure that trial reports are clear and transparent.

PROBLEM/CONDITION: Autism spectrum disorder (ASD). PERIOD COVERED: 2022. DESCRIPTION OF SYSTEM: The Autism and Developmental Disabilities Monitoring Network is an active surveillance program that estimates prevalence and characteristics of ASD and monitors timing of ASD identification among children aged 4 and 8 years. In 2022, a total of 16 sites (located in Arizona, Arkansas, California, Georgia, Indiana, Maryland, Minnesota, Missouri, New Jersey, Pennsylvania, Puerto Rico, Tennessee, Texas [two sites: Austin and Laredo], Utah, and Wisconsin) conducted surveillance for ASD among children aged 4 and 8 years and suspected ASD among children aged 4 years. Surveillance included children who lived in the surveillance area at any time during 2022. Children were classified as having ASD if they ever received 1) an ASD diagnostic statement in a comprehensive developmental evaluation, 2) autism special education eligibility, or 3) an ASD International Classification of Diseases, Ninth Revision (ICD-9) code in the 299 range or International Classification of Diseases, Tenth Revision (ICD-10) code of F84.0, F84.3, F84.5, F84.8, or F84.9. Children aged 4 years were classified as having suspected ASD if they did not meet the case definition for ASD but had an evaluator's suspicion of ASD documented in a comprehensive developmental evaluation. RESULTS: Among children aged 8 years in 2022, ASD prevalence was 32.2 per 1,000 children (one in 31) across the 16 sites, ranging from 9.7 in Texas (Laredo) to 53.1 in California. The overall observed prevalence estimate was similar to estimates calculated using Bayesian hierarchical and random effects models. ASD was 3.4 times as prevalent among boys (49.2) than girls (14.3). Overall, ASD prevalence was lower among non-Hispanic White (White) children (27.7) than among Asian or Pacific Islander (A/PI) (38.2), American Indian or Alaska Native (AI/AN) (37.5), non-Hispanic Black or African American (Black) (36.6), Hispanic or Latino (Hispanic) (33.0), and multiracial children (31.9). No association was observed between ASD prevalence and neighborhood median household income (MHI) at 11 sites; higher ASD prevalence was associated with lower neighborhood MHI at five sites.Record abstraction was completed for 15 of the 16 sites for 8,613 children aged 8 years who met the ASD case definition. Of these 8,613 children, 68.4% had a documented diagnostic statement of ASD, 67.3% had a documented autism special education eligibility, and 68.9% had a documented ASD ICD-9 or ICD-10 code. All three elements of the ASD case definition were present for 34.6% of children aged 8 years with ASD.Among 5,292 (61.4% of 8,613) children aged 8 years with ASD with information on cognitive ability, 39.6% were classified as having an intellectual disability. Intellectual disability was present among 52.8% of Black, 50.0% of AI/AN, 43.9% of A/PI, 38.8% of Hispanic, 32.7% of White, and 31.2% of multiracial children with ASD. The median age of earliest known ASD diagnosis was 47 months and ranged from 36 months in California to 69.5 months in Texas (Laredo).Cumulative incidence of ASD diagnosis or eligibility by age 48 months was higher among children born in 2018 (aged 4 years in 2022) than children born in 2014 (aged 8 years in 2022) at 13 of the 15 sites that were able to abstract records. Overall cumulative incidence of ASD diagnosis or eligibility by age 48 months was 1.7 times as high among those born in 2018 compared with those born in 2014 and ranged from 1.4 times as high in Arizona and Georgia to 3.1 times as high in Puerto Rico. Among children aged 4 years, for every 10 children meeting the case definition of ASD, one child met the definition of suspected ASD.Children with ASD who were born in 2018 had more evaluations and identification during ages 0-4 years than children with ASD who were born in 2014 during the 0-4 years age window, with an interruption in the pattern in early 2020 coinciding with onset of the COVID-19 pandemic.Overall, 66.5% of children aged 8 years with ASD had a documented autism test. Use of autism tests varied widely across sites: 24.7% (New Jersey) to 93.5% (Puerto Rico) of children aged 8 years with ASD had a documented autism test in their records. The most common tests documented for children aged 8 years were the Autism Diagnostic Observation Schedule, Autism Spectrum Rating Scales, Childhood Autism Rating Scale, Gilliam Autism Rating Scale, and Social Responsiveness Scale. INTERPRETATION: Prevalence of ASD among children aged 8 years was higher in 2022 than previous years. ASD prevalence was higher among A/PI, Black, and Hispanic children aged 8 years than White children aged 8 years, continuing a pattern first observed in 2020. A/PI, Black, and Hispanic children aged 8 years with ASD were also more likely than White or multiracial children with ASD to have a co-occurring intellectual disability. Identification by age 48 months was higher among children born in 2018 compared with children born in 2014, suggesting increased early identification consistent with historical patterns. PUBLIC HEALTH ACTION: Increased identification of autism, particularly among very young children and previously underidentified groups, underscores the increased demand and ongoing need for enhanced planning to provide equitable diagnostic, treatment, and support services for all children with ASD. The substantial variability in ASD identification across sites suggests opportunities to identify and implement successful strategies and practices in communities to ensure all children with ASD reach their potential.

Leptospirosis (caused by pathogenic bacteria in the genus Leptospira) is prevalent worldwide but more common in tropical and subtropical regions. Transmission can occur following direct exposure to infected urine from reservoir hosts, or a urine-contaminated environment, which then can serve as an infection source for additional rats and other mammals, including humans. The brown rat, Rattus norvegicus, is an important reservoir of Leptospira spp. in urban settings. We investigated the presence of Leptospira spp. among brown rats in Boston, Massachusetts and hypothesized that rat population dynamics in this urban setting influence the transportation, persistence, and diversity of Leptospira spp. We analyzed DNA from 328 rat kidney samples collected from 17 sites in Boston over a seven-year period (2016-2022); 59 rats representing 12 of 17 sites were positive for Leptospira spp. We used 21 neutral microsatellite loci to genotype 311 rats and utilized the resulting data to investigate genetic connectivity among sampling sites. We generated whole genome sequences for 28 Leptospira spp. isolates obtained from frozen and fresh tissue from some of the 59 positive rat kidneys. When isolates were not obtained, we attempted genomic DNA capture and enrichment, which yielded 14 additional Leptospira spp. genomes from rats. We also generated an enriched Leptospira spp. genome from a 2018 human case in Boston. We found evidence of high genetic structure among rat populations that is likely influenced by major roads and/or other dispersal barriers, resulting in distinct rat population groups within the city; at certain sites these groups persisted for multiple years. We identified multiple distinct phylogenetic clades of L. interrogans among rats that were tightly linked to distinct rat populations. This pattern suggests L. interrogans persists in local rat populations and its transportation is influenced by rat population dynamics. Finally, our genomic analyses of the Leptospira spp. detected in the 2018 human leptospirosis case in Boston suggests a link to rats as the source. These findings will be useful for guiding rat control and human leptospirosis mitigation efforts in this and other similar urban settings.

Critical appraisal of the quality of randomised trials is possible only if their design, conduct, analysis, and results are completely and accurately reported. Without transparent reporting of the methods and results, readers will not be able to fully evaluate the reliability and validity of trial findings. The CONSORT (Consolidated Standards of Reporting Trials) statement aims to improve the quality of reporting and provides a minimum set of items to be included in a report of a randomised trial. CONSORT was first published in 1996 and was updated in 2001 and 2010. CONSORT comprises a checklist of essential items that should be included in reports of randomised trials and a diagram for documenting the flow of participants through a trial. The CONSORT statement has been updated (CONSORT 2025) to reflect recent methodological advancements and feedback from end users, ensuring that it remains fit for purpose. Here, we present the updated CONSORT explanation and elaboration document, which has been extensively revised and describes the rationale and scientific background for each CONSORT 2025 checklist item and provides published examples of good reporting. The objective is to enhance the use, understanding, and dissemination of CONSORT 2025 and provide guidance to authors about how to improve the reporting of their trials and ensure trial reports are complete, and transparent.

IMPORTANCE: Well-designed and properly executed randomized trials are considered the most reliable evidence on the benefits of health care interventions. However, there is overwhelming evidence that the quality of reporting is not optimal. The CONSORT (Consolidated Standards of Reporting Trials) statement was designed to improve the quality of reporting and provides a minimum set of items to be included in a report of a randomized trial. CONSORT was first published in 1996, then updated in 2001 and 2010. Herein, we present the updated CONSORT 2025 statement, which aims to account for recent methodological advancements and feedback from end users. OBSERVATIONS: We conducted a scoping review of the literature and developed a project-specific database of empirical and theoretical evidence related to CONSORT to generate a list of potential changes to the checklist. The list was enriched with recommendations provided by the lead authors of existing CONSORT extensions (harms, outcomes, nonpharmacological treatment), other related reporting guidelines (Template for Intervention Description and Replication [TIDieR]), and recommendations from other sources (eg, personal communications). The list of potential changes to the checklist was assessed in a large, international, online, 3-round Delphi survey involving 317 participants and discussed at a 2-day online expert consensus meeting of 30 invited international experts. We have made substantive changes to the CONSORT checklist. We added 7 new checklist items, revised 3 items, deleted 1 item, and integrated several items from key CONSORT extensions. We also restructured the CONSORT checklist, with a new section on open science. The CONSORT 2025 statement consists of a 30-item checklist of essential items that should be included when reporting the results of a randomized trial and a diagram for documenting the flow of participants through the trial. To facilitate implementation of CONSORT 2025, we have also developed an expanded version of the CONSORT 2025 checklist, with bullet points eliciting critical elements of each item. CONCLUSIONS AND RELEVANCE: Authors, editors, reviewers, and other potential users should use CONSORT 2025 when writing and evaluating manuscripts of randomized trials to ensure that trial reports are clear and transparent.

BACKGROUND: Since 2013, national trends in behavioral factors that increase STI risk among adolescent and young adult (A/YA) females have been mixed (e.g., fewer sex partners, lower condom use). We used data from a national sample of A/YA females to examine racial disparities in CT prevalence considering these trends. METHODS: Using 2011-March 2020 National Health and Nutrition Examination Survey data, we estimated the prevalence, unadjusted and adjusted prevalence ratios (APRs) of a positive CT urine test among sexually experienced non-Hispanic Black (Black), Hispanic, non-Hispanic Other race (NHO), and non-Hispanic White (White) A/YA females. Percentages were categorized by race/ethnicity, and each compared to the average of the other race/ethnic groups (e.g., Black vs. Hispanic, NHO and White). Covariates included age group, health insurance coverage, number of sex partners and condom use (both past year). RESULTS: Overall, the prevalence of CT infection among A/YA females was 5.8% (95% CI: 4.5%-7.3%). CT prevalence was higher among Black females (vs. Hispanic, NHO, and White) (11.7%; 95%CI: 8.7%-15.2%) and lower among White females (vs. Black, Hispanic, and NHO) (3.2%; 95%CI: 1.7%-5.5%). Compared with the average CT prevalence for Hispanic, NHO, and White females, Black females had a higher adjusted CT prevalence (APR: 2.48, 95%CI: 1.63-3.75). CONCLUSIONS: Nationally, CT prevalence was 2.5 times as high among Black A/YA females than the average prevalence for Hispanic, NHO, and White females. Inclusion of behavioral STI risk factors did not attenuate this association. Research incorporating sexual network-level factors associated with CT transmission may provide additional insights.

IMPORTANCE: Invasive group A Streptococcus (GAS) infections are associated with substantial morbidity, mortality, and economic burden. OBJECTIVE: To update trends in invasive GAS disease incidence rates in 10 US states between 2013 and 2022. DESIGN, SETTING, AND PARTICIPANTS: Clinical, demographic, and laboratory data for invasive GAS cases were collected as part of population-based surveillance in the Active Bacterial Core surveillance network covering 34.9 million persons across 10 US states. A case was defined as isolation of GAS from a normally sterile site or from a wound in a patient with necrotizing fasciitis or streptococcal toxic shock syndrome between January 1, 2013, and December 31, 2022. Demographic and clinical data were collected from medical record review. From 2013 to 2014, available isolates were emm typed and antimicrobial susceptibilities determined using conventional methods; from 2015 onward, whole-genome sequencing was used. MAIN OUTCOMES AND MEASURES: Incidence rates by sex, age, race, and selected risk factors; clinical syndromes, outcomes, and underlying patient conditions; and isolate characteristics, including antimicrobial susceptibility. RESULTS: Surveillance in 10 US states identified 21 312 cases of invasive GAS from 2013 through 2022, including 1981 deaths. The majority of cases (57.5%) were in males. Among case-patients, 1272 (6.0%) were aged 0 to 17 years, 13 565 (63.7%) were aged 18 to 64 years, and 6474 (30.4%) were 65 years or older; 5.5% were American Indian or Alaska Native, 14.3% were Black, and 67.1% were White. Incidence rose from 3.6 per 100 000 persons in 2013 to 8.2 per 100 000 persons in 2022 (P < .001 for trend). Incidence was highest among persons 65 years or older; however, the relative increase over time was greatest among adults aged 18 to 64 years (3.2 to 8.7 per 100 000 persons). Incidence was higher among American Indian or Alaska Native persons than in other racial and ethnic groups. People experiencing homelessness, people who inject drugs, and residents of long-term care facilities had substantially elevated GAS incidence rates. Among tested isolates, those nonsusceptible to macrolides and clindamycin increased from 12.7% in 2013 to 33.1% in 2022. CONCLUSIONS: Invasive GAS infections increased substantially in 10 US states during a surveillance period from 2013 to 2022. Accelerated efforts to prevent and control GAS are needed, especially among groups at highest risk of infection.

During the 2023-2024 respiratory syncytial virus (RSV) season, vaccination was recommended for adults ≥60 years based on shared clinical decision-making with their healthcare providers. We examined RSV vaccine uptake and characteristics associated with uptake among age-eligible Kaiser Permanente Southern California (KPSC) patients. Our study cohort included all patients ≥60 years from September 23, 2023 (i.e., date RSV vaccination first became available at KPSC; N = 1,003,132) to April 9, 2024 (i.e., end of local RSV season). To identify sociodemographic and clinical characteristics associated with RSV vaccination, we used multivariable robust Poisson regression to estimate the adjusted relative risk (aRR) and 95 % CI. Overall, 7.6 % of patients were vaccinated for RSV. In multivariable regression analyses, those aged 70-79.9 years (aRR: 1.36; 95 % CI: 1.34-1.39) and aged ≥80 years (aRR: 1.35; 95 % CI: 1.32-1.38) were more likely to be vaccinated, compared with those aged 60-69.9 years. Compared with Non-Hispanic White patients, Asian (aRR: 0.95; 95 % CI: 0.93-0.97), Hispanic (aRR: 0.52; 95 % CI: 0.51-0.54), Non-Hispanic Black (aRR: 0.69; 95 % CI: 0.67-0.71), Pacific Islander (aRR: 0.91; 95 % CI: 0.84-0.98), and Native American or Alaska Native (aRR: 0.80; 95 % CI: 0.70-0.92) patients were less likely to be vaccinated. Those in higher neighborhood deprivation quartiles were less likely to be vaccinated (Q2: aRR: 0.86; 95 % CI: 0.85-0.88; Q3: aRR: 0.77; 95 % CI: 0.76-0.79; and Q4: aRR: 0.67; 95 % CI: 0.65-0.68), compared with those in the lowest deprivation quartile. We found low vaccination uptake and identified disparities in vaccination that might exacerbate existing disparities in RSV infection and severe RSV disease among certain populations. CDC's ACIP recently updated their recommendations for all adults 75+ years, and this might begin to address these disparities.

Introduction: Motor-vehicle crash (MVC) deaths increased by a record 10% from 2020 to 2021 in the United States and disproportionately impacted persons of certain racial/ethnic groups. Methods: Mortality data from the National Vital Statistics System was used to describe MVC death rate trends during 2019–2022 by six racial/ethnic groups: non-Hispanic (NH) American Indian or Alaska Native (AIAN), NH Asian, NH Black, NH Native Hawaiian or Other Pacific Islander (NHOPI), NH White, and Hispanic. Age-adjusted death rates per 100,000 population, 95% confidence intervals (CIs), and annual percent change in rates were calculated. Results: Overall MVC death rates increased during 2019–2022, and rates were highest among NH AIAN and NH Black persons across all years. During 2019–2020, death rates increased the most among NH Black persons (+26.0%). During 2020–2021, rates increased among all racial/ethnic groups, with the greatest increase among NH NHOPI persons (+66.7%) and NH AIAN persons (+27.8%). Conclusions: These findings highlight stark differences by racial/ethnic group in MVC death rates and changes in these rates. Between 2019 and 2022, NH AIAN, NH Black, and NH NHOPI populations experienced the largest increases in MVC death rates, although there was large variation in rates and trends. Widespread adoption of a comprehensive suite of prevention strategies, such as the Safe System approach, while targeting subpopulations with the greatest burden of MVC deaths could reduce these differences and the overall burden of MVCs. Practical Applications: These findings show which subpopulations could experience the greatest impacts from transportation safety investments in reducing overall MVC death rates in the United States. © 2025

BACKGROUND: While the estimated number of US influenza-associated deaths is reported annually, detailed data on the epidemiology of influenza-associated deaths, including the burden of in-hospital vs post-hospital discharge deaths, are limited. METHODS: Using data from the 2010-2011 through 2018-2019 seasons from the Influenza Hospitalization Surveillance Network, we linked cases to death certificates to identify patients who died from any cause during their influenza hospital stay or within 30 days post discharge. We described demographic and clinical characteristics of patients who died in the hospital vs post discharge and characterized locations and causes of death (CODs). RESULTS: Among 121 390 cases hospitalized with laboratory-confirmed influenza over 9 seasons, 5.5% died; 76% of deaths were in patients aged ≥65 years, 71% were non-Hispanic White, and 34% had 4 or more underlying medical conditions. Among all patients with an influenza-associated hospitalization who died, 48% of deaths occurred after hospital discharge; the median number of days from discharge to death was 9 (interquartile range, 3-19). Post-discharge deaths more often occurred in older patients and among those with underlying medical conditions. Only 37% of patients who died had "influenza" as a COD on their death certificate. Influenza was more frequently listed as a COD among persons who died in the hospital compared with cardiovascular disease among those who died after discharge. CONCLUSIONS: All-cause mortality burden is substantial among patients hospitalized with influenza, with almost 50% of deaths occurring within 30 days after hospital discharge. Surveillance systems should consider capture of post-discharge outcomes to better characterize the impact of influenza on all-cause mortality.