Maternal respiratory syncytial virus (RSV) vaccine and nirsevimab, a long-acting monoclonal antibody for infants aged 0-7 months and children aged 8-19 months who are at increased risk for severe RSV disease, became widely available for prevention of severe RSV disease among infants and young children during the 2024-25 RSV season. To evaluate the association between availability of these products and infant and child RSV-associated hospitalization rates, the rates among children aged <5 years were compared for the 2024-25 and 2018-20 RSV seasons using data from the RSV-Associated Hospitalization Surveillance Network (RSV-NET) and New Vaccine Surveillance Network (NVSN). Among infants aged 0-7 months (eligible for protection with maternal vaccination or nirsevimab), 2024-25 RSV-associated hospitalization rates were lower compared with 2018-20 pooled rates (estimated relative rate reductions of 43% [RSV-NET: 95% CI = 40%-46%] and 28% [NVSN: 95% CI = 18%-36%]). The largest estimated rate reduction was observed among infants aged 0-2 months (RSV-NET: 52%, 95% CI = 49%-56%; NVSN: 45%, 95% CI = 32%-57%) and during peak hospitalization periods (December-February). These findings support Advisory Committee on Immunization Practices' recommendations for maternal vaccination or nirsevimab to protect against severe RSV disease in infants and highlight the importance of implementing the recommendations to protect infants as early in the RSV season as possible, before peak transmission, and for infants born during the RSV season, within the first week of life, ideally during the birth hospitalization.

BACKGROUND: Infectious diseases (ID) physicians play a crucial role in public health emergencies. Effective collaboration between public health agencies and healthcare providers is essential for a coordinated response. However, there is limited information on how ID physicians and health departments collaborate and which areas need to be improved. Here, we identify ways to enhance public health preparedness through increased collaboration between ID physicians and state, tribal, local, and territorial health departments. METHODS: We performed a secondary qualitative analysis of 37 telephone interviews conducted using a semistructured discussion guide. Interviews were conducted from July 2023 through September 2023 as part of a pandemic preparedness needs assessment by the Infectious Diseases Society of America's COVID-19 Real-Time Learning Network. Participants included ID physicians (n = 13), public health workers (n = 7), healthcare facility-based pandemic leaders (n = 7), and national stakeholders (n = 10). RESULTS: While some jurisdictions had robust connections between ID physicians and public health staff, lack of coordination in other areas led to duplication of efforts, confusion, and underutilization of resources. Respondents indicated that collaboration can be strengthened over time. Recommendations included better data systems, standardized reporting procedures, early dissemination of updates, and training of ID physicians in the incident command structure and media communication. CONCLUSIONS: The opportunity to build on institutional knowledge from the coronavirus disease 2019 pandemic will be lost without a commitment of time, resources, and planning. Public health officials can use this experience as a catalyst for building strong collaborative relationships between ID physicians and public health practitioners, a cornerstone of future pandemic response.

Allergic fungal rhinosinusitis (AFRS) is a unique endotype of chronic rhinosinusitis with nasal polyps (CRSwNP). Despite high recurrence rates and often more severe presenting signs compared with other subtypes of CRSwNP, research dedicated to AFRS has been lacking. Diagnostic criteria are outdated, the mechanistic relationship of AFRS to other associated diseases is unclear, and the pathophysiology of disease and risk factors for recurrence have not been well studied. In December 2023, a multidisciplinary group of rhinologists, otolaryngologists, pulmonologists, allergists, immunologists, scientists, and infectious disease experts met at the National Institute of Health to discuss unmet needs for future AFRS research and care, including patient management, diagnostic criteria, severity, pathophysiology, and related conditions. A summary of these clinical and associated research discussions is included below.

BACKGROUND: In 2020, a pilot program for hypertension control was initiated in primary care facilities in Lampang Province, Thailand. The program followed the framework of the HEARTS program for standardized hypertension treatment, but the financial costs of the program are not well understood. This study evaluates the costs of the HEARTS approach compared to usual care to inform future scale-up efforts of the program. METHODS: Cost data were collected and analyzed using the HEARTS costing tool, a Microsoft Excel-based tool that supports activity-based costing of the HEARTS program from the health system perspective. Three scenarios were considered: usual care, the HEARTS regimen using standardized hypertension treatment with single-agent pills, and a sub-scenario of the HEARTS regimen using single-pill dual-drug combination pills. Costs are estimated as annual costs from the health system perspective in all Lampang primary care facilities. RESULTS: For the usual care scenario, the HEARTS single-pill scenario, and the HEARTS combination-pill sub-scenario, the average annual medication cost per treated patient was USD 14.0 (THB 485), USD 13.8 (THB 479), and USD 14.3 (THB 497), respectively. Total program cost per primary care user was USD 13.6 (THB 472.7), THB USD 14.3 (494.5), and USD 14.4 (THB 499.9) across the three scenarios, respectively. The largest program cost driver (45-47% across the examined scenarios) was attributed to a comprehensive package of laboratory tests applied to all hypertension patients. Hypothetically, reducing test coverage from all hypertension patients (27% of primary care users) to 15% of primary care users (corresponding to the proportion of patients aged 65+) would reduce program cost per user from USD 14.3 to USD 12.0 in the HEARTS combination-pill scenario. CONCLUSIONS: Compared to usual care, HEARTS implementation costs include additional costs for staff training, which are balanced by lower medication expenditures using the HEARTS standardized regimen with single-agent pills. The HEARTS regimen using dual-drug combination pills was estimated to be slightly more costly due to the higher price of combination pills. Optimizing coverage of diagnostic tests and lowering the purchasing prices of combination-pill medicines are key areas for cost reduction in future scale-up efforts.

BACKGROUND: Low pressure events (LPEs), defined as a water service disruption that presumably lowers system water pressure, can cause drinking water contamination resulting in increased illness risk to consumers. OBJECTIVES: Examine whether LPEs increase the risk for highly credible acute gastrointestinal illness (HCGI) and acute respiratory illness (ARI) and compare water quality in exposed and unexposed areas in the United States. METHODS: A matched cohort study was conducted during 2015-2019. For each LPE, household survey exposed areas were matched 1:2 with unexposed areas based on water main size and material at the point of repair, as well as the housing type and demographic characteristics of the local population from the most recent census tract. Water samples were collected to monitor physicochemical and microbiological water quality parameters. Households (HHs) were surveyed about water use and illness during the 2 weeks after the LPE. Multivariable log-binomial models clustered on utility and LPE number were used to investigate associations between LPE exposure and HCGI and ARI. RESULTS: Five water utilities reported 58 LPEs, including planned maintenance (76%) and emergency (24%) events. Controlling for livestock near home, private well presence, number of people in HH, and travel away from home, exposed HH were at higher risk of HCGI compared to unexposed HH (risk ratio =1.20; 95%CI: 1.05,1.37). No associations between LPE and ARI were detected. Certain LPEs characteristics like pipe material, size, and depth were associated with an increased HH HCGI risk. HHs experiencing LPEs where low disinfectant residual, high adenosine triphosphate, or general Bacteroidales were detected in water following an LPE repair were also at a higher risk for HCGI. CONCLUSIONS: LPEs were associated with 20% higher risk of HCGI in HHs. Planned improvements to water distribution system infrastructure, adherence to industry standard distribution repair practices, and water monitoring following pipe repairs could supplement community alert systems to reduce illnesses from LPEs. https://doi.org/10.1289/EHP15564.

BACKGROUND: We estimated RSV and hMPV illness incidences among pregnant women and examined the association between antenatal RSV illness and preterm birth and small for gestational age (SGA). METHODS: Pregnant women aged ≥18 years were followed twice weekly until the end of pregnancy to identify illness episodes with >1 of myalgia, cough, runny nose/nasal congestion, sore throat, or difficulty breathing. Mid-turbinate nasal swabs were collected and tested for RSV and hMPV by real-time reverse-transcription PCR. Incidences were calculated. Cox proportional hazards regression was used to estimate hazard ratios (HRs) comparing participants with and without RSV illnesses for preterm birth (live birth before 37 weeks gestation) and SGA infant. RESULTS: Among 2,764 participants, the median age was 29 years (interquartile range [IQR] 24-34) and the median enrollment gestational age was 10 weeks (IQR 7-14). Overall, 71 (3%) and 29 (1%) cases of RSV and hMPV illnesses were identified, respectively. Among these, 30 (42%) and 10 (34%), respectively, sought medical care. Incidence rates per 10,000 pregnant woman-months were 57 (95% confidence interval [CI] 44-72) for RSV and 23 (95% CI 16-33) for hMPV illnesses. Antenatal RSV illness in the third trimester conferred an increased risk of preterm birth (adjusted HR [aHR] 2.50, 95% CI 1.04-6.00) but not having an SGA infant (aHR 0.79, 95% CI 0.29 to 2.16). CONCLUSIONS: Antenatal RSV illness was associated with some adverse antenatal outcomes. Pregnant women had a 0.4-0.7% risk of RSV illness per pregnancy month, of which one third resulted in medical visits.

Drug-resistant shigellosis is increasing, particularly among men who have sex with men (MSM). During July-October 2022, an extended-spectrum β-lactamase-producing Shigella sonnei cluster of 9 patients was identified in Chicago, of whom 8 were MSM and 6 were festival attendees. The cluster also included 4 domestic travelers to Chicago. Sexual health care for MSM should include shigellosis diagnosis and prevention.

BACKGROUND: Household transmission of respiratory viruses may drive community spread. Few recent studies have examined household respiratory syncytial virus (RSV) transmission in the United States. METHODS: We conducted a prospective community-based cohort study from 1 June 2022 to 31 May 2023. Participants had blood samples collected and completed nasal swabs and surveys at least weekly, irrespective of symptoms. We tested serum for RSV antibody, nasal swabs by quantitative reverse transcription polymerase chain reaction (RT-qPCR), and performed whole genome sequencing. We evaluated secondary RSV transmission and associated risk factors based on a log-linear Poisson regression model. RESULTS: RSV was detected among 310 (10%) participants within 200 (20%) households. Most (94%) index cases were symptomatic. We identified 37 cases of potential secondary transmission within 14 days of a distinct index case (10%, 95% confidence interval [CI]: 7%, 14%); median age of index and secondary cases were 6 (interquartile range [IQR]: 3-10) and 35 (7-41) years, respectively, with 89% (24/27) of index cases aged 6 months to 12 years. Factors associated with increased risk of RSV transmission included index case viral detection ≥1 week and contact age ≤12 years. Of 120 sequenced specimens, the main lineages represented were A.d.5.2 (n = 37) and A.d.1 (n = 30). Sequenced viruses from households with ≥2 RSV infections were similar when occurring within ≤14 days (mean pairwise difference 4 [range 0-13], n = 17 households), compared to those >14 days (137 [37-236], n = 2). CONCLUSIONS: Most RSV household transmission occurs from infants and young children to adults. Viral genome sequencing demonstrated that multiple household infections within a 14-day period are likely due to within-household transmission.

BACKGROUND: Although numerous studies have demonstrated the effectiveness of interventions delivered by disease intervention specialists (DIS), relatively few studies have assessed their economic outcomes. We performed a systematic literature review of the cost, cost-effectiveness, and cost-benefit of DIS-delivered interventions for sexually transmitted infections (STIs) in the United States. METHODS: Building on a recent systematic review of the effectiveness of DIS-delivered interventions, we reviewed economic outcomes associated with these interventions for STIs. We searched articles indexed in MEDLINE, Web of Science, CINAHL, and ProQuest from 2000 through December 2022, using these inclusion criteria: addressed an intervention of DIS-delivered interventions for STIs including partner services; United States setting; and included estimates for program cost, cost-effectiveness, or cost-benefit. Findings were summarized through narrative synthesis. RESULTS: Seven studies met the inclusion criteria. Overall, DIS-delivered interventions including STI partner services can be a cost-effective use of public health resources. In some scenarios, the cost of these interventions can be completely offset by averted medical costs. Cost and cost-effectiveness estimates of DIS-delivered interventions can vary across geographic settings and under different epidemiologic conditions. CONCLUSIONS: Although scarce, the available evidence suggests DIS-delivered interventions including STI partner services are an efficient use of public health resources. Health economic modeling studies are needed to facilitate conversion of intermediate cost-effectiveness outcomes (e.g., cost per syphilis case identified and treated) into standard cost-effectiveness outcomes (e.g., cost per quality-adjusted life year [QALY] gained).

Occupational exoskeletons (EXOs) have received growing attention as a new ergonomic intervention to reduce physical demands in various industries (e.g., manufacturing, logistics, construction, and agriculture). However, their potential use in mining has not yet been reported. Survey data (n = 135) were obtained from mining workers in the United States (US) and Indonesia (ID). Qualitative and frequency analyses were used to summarize and compare respondents’ perceived barriers, benefits, and promoters to EXO use and adoption. Beta regression analyses were also used to examine whether the perceived likelihood to use arm-support EXOs or back-support EXOs differed between the countries and was affected by demographic or job characteristics, or by perceptions regarding EXOs. Both US and ID respondents reported potential benefits of EXOs for physically demanding tasks such as lifting and overhead work, and they shared concerns about adaptation, uncertainty or lack of knowledge, confined spaces, device weight, potential failure or damage, and costs. However, some key differences also emerged: US respondents were more likely to consider using arm-support EXOs and back-support EXOs, despite expressing concerns about their use; ID respondents, although they reported more existing health and safety hazards, appeared more hesitant about adopting EXOs, possibly due to these additional hazards. These results demonstrate that miners appear to have an interest in EXOs but also emphasize the need to ensure task compatibility, comfort, and affordability to ensure the safe and effective adoption of EXO technology in mining in both developed and developing countries. © The Author(s) 2025.

OBJECTIVE: A firefighter wears a standard safety coat, its model unchanged for many years, when tackling a fire. We designed a new cooling system coat with carbon nano tube-based fabric and pouches inside the coat for coolants and fans. The coats, one standard and the other still evolving, are compared on several metrics including core body temperature and thermal comfort. METHODS: An experimental protocol was designed involving a live burn facility under the paradigm of non-inferiority study with firefighters trying both coats. The metrics are measured at several phases of the protocol. Multivariate t-test is used to compare the performance of the coats. RESULTS: The new coat is not inferior to the standard coat. CONCLUSION: The new coat in its final form, which is yet to be tested fully, is a plausible replacement for the standard coat.

OBJECTIVE: West Nile virus (WNV) is the most common cause of arboviral disease in the United States. Approximately 1% of infections involve the nervous system, most commonly resulting in West Nile encephalitis (WNE), West Nile meningitis (WNM), or acute flaccid paralysis (AFP). METHODS: In this systematic review, we characterized comprehensively the diagnostic and clinical features of WNV neuroinvasive disease (WNND) in the United States, as well as the evidence regarding prognostic factors and long-term outcomes of WNND. RESULTS: We identified 47 relevant studies reporting data on acute or longitudinal features of WNND. Across studies, the most common presenting symptoms were fever (88%), nausea/vomiting (58%), and fatigue (50%) coupled neurologically with headache (50%), altered mental status (39%), and focal weakness (32%). Pooled mortality was 9.2%, and 42.1% of reported cases required intensive care unit (ICU) admission. In meta-analyses, chronic kidney disease (odds ratio [OR] = 5.99, 95% confidence interval [CI] = 2.71-13.23), diabetes mellitus (OR = 2.43, 95% CI = 1.54-3.84), and hypertension (OR = 4.01, 95% CI = 2.39-6.72) were associated with an increased risk of mortality. Multidomain neurocognitive impairment was reported in several studies at post-hospitalization follow-up, although with marked heterogeneity between study methodology. Subjective neurocognitive impairment, most notably fatigue (37-75%), memory concerns (11-57%), concentration deficits (17-48%), and depression (17-38%), were also common at post-hospitalization follow-up. INTERPRETATION: These findings underscore the significant mortality and morbidity of WNND in the acute and long-term setting. Our findings may additionally provide utility for risk stratification of hospitalized patients with WNND and suggest the need for further evaluation of novel therapeutics to prevent substantial disease-associated acute and long-term disability. ANN NEUROL 2025.

BACKGROUND: Gestational exposure to non-persistent endocrine-disrupting chemicals (EDCs) may be associated with adverse pregnancy outcomes. While many EDCs affect the endocrine system, their effects on endocrine-related metabolic pathways remain unclear. This study aims to explore the global metabolome changes associated with EDC biomarkers at delivery. METHODS: This study included 75 pregnant individuals who delivered at the University of Cincinnati Hospital from 2014 to 2017. We measured maternal urinary biomarkers of paraben/phenol (12), phthalate (13), and phthalate replacements (4) from the samples collected during the delivery visit. Global serum metabolome profiles were analyzed from maternal blood (n = 72) and newborn (n = 63) cord blood samples collected at delivery. Fifteen of the 29 urinary biomarkers were excluded due to low detection frequency or potential exposures during hospital stay. We assessed metabolome-wide associations between 14 maternal urinary biomarkers and maternal/newborn metabolome profiles. Additionally, performed enrichment analysis to identify potential alterations in metabolic pathways. RESULTS: We observed metabolome-wide associations between maternal urinary concentrations of phthalate metabolites (mono-isobutyl phthalate), phthalate replacements (mono-2-ethyl-5-carboxypentyl terephthalate, mono-2-ethyl-5-hydroxyhexyl terephthalate) and phenols (bisphenol-A, bisphenol-S) and maternal serum metabolome, using q-value < 0.2 as a threshold. Additionally, associations of phthalate metabolites (mono-n-butyl phthalate, monobenzyl phthalate) and phenols (2,5-dichlorophenol, BPA) with the newborn metabolome were noted. Enrichment analyses revealed associations (p-gamma < 0.05) with amino acid, carbohydrate, lipid, glycan, vitamin, and other cofactor metabolism pathways. CONCLUSION: Maternal paraben, phenol, phthalate, and phthalate replacement biomarker concentrations at delivery were associated with maternal and newborn serum global metabolome.

BACKGROUND: Understanding the risk of hospitalization from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can guide effective public health interventions and severity assessments. This study calculated infection-hospitalization ratios (IHRs) and infection-case ratios (ICRs) to understand the relationship between SARS-CoV-2 infections, cases, and hospitalizations among different age groups during periods of Delta and Omicron variant predominance. METHODS: After calculating antinucleocapsid SARS-CoV-2 antibody seroprevalence using residual commercial laboratory serum specimens, 2 ratios were computed: (1) IHRs using coronavirus disease 2019 hospitalization data and (2) ICRs using Centers for Disease Control and Prevention surveillance data. Ratios were calculated across age groups (0-17, 18-49, 50-69, and ≥70 years) for 2 time periods (September-December 2021 [Delta] and December 2021-February 2022 [Omicron]). RESULTS: Pediatric IHRs increased from 76.7 during Delta to 258.4 during Omicron. Adult IHRs ranged from 3.0 (≥70 years) to 21.6 (18-49 years) during Delta and from 10.0 (≥70 years) to 119.1 (18-49 years) during Omicron. The pediatric ICR was lower during the Delta period (2.7) compared with the Omicron period (3.7). Adult ICRs (Delta: 1.1 [18-49 years] to 2.1 [70+ years]; Omicron: 2.2 [>70+ years] to 2.9 [50-69 years]) were lower than pediatric ICRs during both time periods. CONCLUSIONS: All age groups exhibited a lower proportion of infections associated with hospitalization in the Omicron period than the Delta period; the proportion of infections associated with hospitalization increased with each older age group. A lower proportion of SARS-CoV-2 infections were associated with reported cases in the Omicron period than in the Delta period among all age groups.

BACKGROUND: Globally, over one-third of pulmonary tuberculosis (TB) disease diagnoses are made based on clinical criteria after a negative bacteriological test result. There is limited information on the factors that determine clinicians' decisions to initiate TB treatment when initial bacteriological test results are negative. METHODS AND FINDINGS: We performed a systematic review and individual patient data meta-analysis using studies conducted between January 2010 and December 2022 (PROSPERO: CRD42022287613). We included trials or cohort studies that enrolled individuals evaluated for TB in routine settings. In these studies, participants were evaluated based on clinical examination and routinely used diagnostics and were followed for ≥1 week after the initial test result. We used hierarchical Bayesian logistic regression to identify factors associated with treatment initiation following a negative result on an initial bacteriological test (e.g., sputum smear microscopy (SSM), Xpert MTB/RIF). Multiple factors were positively associated with treatment initiation: male sex [adjusted odds ratio (aOR) 1.61 (1.31, 1.95)], history of prior TB [aOR 1.36 (1.06, 1.73)], reported cough [aOR 4.62 (3.42, 6.27)], reported night sweats [aOR 1.50 (1.21, 1.90)], and having HIV infection but not on ART [aOR 1.68 (1.23, 2.32)]. Treatment initiation was substantially less likely for individuals testing negative with Xpert [aOR 0.77 (0.62, 0.96)] compared to smear microscopy and declined in more recent years. We were not able assess why clinicians made treatment decisions, as these data were not available. CONCLUSIONS: Multiple factors influenced decisions to initiate TB treatment despite negative test results. Clinicians were substantially less likely to treat in the absence of a positive test result when using more sensitive, PCR-based diagnostics.

Novichok nerve agents, such as A-230, A-232, and A-234, were classified as Schedule 1 chemicals under the Chemical Weapons Convention (CWC) by the Organisation for the Prohibition of Chemical Weapons (OPCW) following poisoning incidents in 2018. As a result, the production, storage, and use of these chemicals are strictly prohibited by CWC signatory nations. The identification of biomarkers indicating Novichok exposure in humans is crucial for prompt detection and response to potential incidents involving these banned chemical weapons. In this study, BChE was isolated from human serum samples exposed to Novichok nerve agents in vitro using immunomagnetic capture, followed by enzymatic digestion with Pronase or proteinase K to generate new peptide biomarkers indicative of exposure. We identified nine previously unpublished Novichok-adducted peptides generated through enzymatic digestion with proteinase K and Pronase using liquid chromatography-high-resolution mass spectrometry. Two peptides, [Agent]-serine-alanine for proteinase K digestion and [Agent]-serine-alanine-glycine for Pronase digestion, were selected for optimization due to their abundance. The analysis was subsequently transferred to an LC-triple quadrupole system to enhance throughput and detect these new biomarkers at the limits of detection corresponding to BChE inhibition levels of 3.90% or less. These additional biomarkers can improve laboratory preparedness for OPCW-designated biomedical testing laboratories as well as other clinical and investigative laboratories tasked with responding to emergencies involving these highly toxic chemicals.

INTRODUCTION: Adverse childhood experiences (ACEs) are preventable, potentially traumatic events that occur in childhood. Alcohol use during pregnancy can result in miscarriage, stillbirth, preterm birth, and a range of lifelong behavioral, intellectual, and physical disabilities in the child. Limited research has examined the relationship between ACEs and alcohol use in pregnancy; available studies might not reflect current trends in this relationship. METHODS: Using 2019-2023 Behavioral Risk Factor Surveillance System data from 41 U.S. jurisdictions, the prevalence of self-reported current alcohol use among pregnant persons aged 18-49 years (N = 2371) was estimated by ACEs and selected characteristics. We calculated unadjusted and adjusted prevalence ratios (aPR) for the relationship between ACEs and alcohol use during pregnancy. RESULTS: The prevalence of current alcohol use was 16.2 % (95 % CI = 11.5-20.9) among pregnant persons who reported experiencing four or more ACEs, and 8.6 % (95 % CI = 5.7-11.5) among those who reported no ACEs. When adjusting for sociodemographic characteristics, pregnant persons who reported four or more ACEs were more likely to report current alcohol use compared to those who reported no ACEs (aPR = 1.8, 95 % CI = 1.1-2.9). Individually, pregnant persons who experienced emotional abuse (aPR = 1.9, 95 % CI = 1.3-2.7) and witnessed intimate partner violence (aPR = 1.6, 95 % CI = 1.1-2.4) were more likely to use alcohol during pregnancy compared to pregnant persons who did not report experiencing these ACEs. CONCLUSIONS: Higher ACE exposure was associated with alcohol use during pregnancy. Steps can be taken to mitigate their potential harms. Clinical and community-level interventions can address ACEs, which might reduce alcohol use during pregnancy.

OBJECTIVE: The resurgence of syphilis in the United States presents a significant public health challenge. Much of the information needed for syphilis surveillance resides in electronic health records (EHRs). In this manuscript, we describe a surveillance platform for automating the extraction of EHR data, known as SmartChart Suite, and the results from a pilot. MATERIALS AND METHODS: The SmartChart Suite framework has been developed in compliance with the HHS Health IT Alignment Policy. The platform's major functionalities are (1) data retrieval; (2) logical evaluation; (3) standardized data storage; and (4) results display. The SmartChart Suite was deployed in September 2023 at the Grady Health System in Atlanta, Georgia. We established a cohort of likely syphilis patients, randomly selected 50 medical records for manual and automated chart review, and analyzed the results. RESULTS: The SmartChart Suite was successfully deployed and integrated with the Epic EHR system at Grady. The overall performance results were precision of 97.6%, recall of 100.0%, and F-Score of 98.8. DISCUSSION: Automated abstraction of EHR data has significant potential to improve public health surveillance and case investigation processes while reducing the resource burden on health departments and reporters. The SmartChart Suite comprises a flexible open-source solution for registry development and maintenance across a wide spectrum of conditions and use cases. CONCLUSION: SmartChart Suite demonstrates the potential of automated chart abstraction to support disease surveillance. HHS-compliant open-source tools such as SmartChart Suite can support more efficient human review by providing accurate and relevant data for critical public health activities.

Background: Our simulations previously predicted focal areas of gaseous pollutant dose delivered to the airway mucosa of a patient with idiopathic pulmonary fibrosis (IPF). We hypothesize a relation between these dose predictions and clinically meaningful endpoints in IPF which link toxicant-driven epithelial injury and disrepair to IPF etiology and pathogenesis. Objective: To determine associations between patient-specific modeling of tracheal geometry, computer simulations of toxicant dose, and lung histopathology in patients with IPF. Methods: The first three conducting airway generations of ten patients diagnosed with IPF were reconstructed from their high-resolution CT chest scans. We quantified geometric abnormalities of the reconstructed tracheas based on their curvature and eccentricity (cross-sectional flattening), and performed three-dimensional computer simulations to predict the average and upper values (i.e. hotspots) of reactive toxicant dose to the underlying mucosa. Distal biopsy tissue samples were characterized by epithelial cell phenotype, extent of fibrosis, and histopathologic severity scores. Non-parametric correlation analysis examined associations between these descriptors. Results: Computed values for curvature and eccentricity of IPF-deformed trachea varied widely among patients and correlated with more subjective rankings of tracheal deformation, and with predicted toxicant dose. Overall histopathologic severity was positively correlated with tracheal deformation and upper decile toxicant uptake. Tracheal curvature was significantly correlated with fibroblastic foci. Conclusions: These results demonstrate an association of tracheal curvature with predicted toxicant dose and with histopathologic indicators in distal tissue. This suggests that these measures may be predictors of risk for acute IPF exacerbations, subsequent clinical deterioration, and disease progression. © 2024

BACKGROUND: Egg-based inactivated quadrivalent seasonal influenza vaccine (eIIV4), cell culture-based inactivated quadrivalent seasonal influenza vaccine (ccIIV4), and recombinant haemagglutinin (HA)-based quadrivalent seasonal influenza vaccine (RIV4) have been licensed for use in the USA. In this study, we used antigen-specific serum proteomics analysis to assess how the molecular composition and qualities of the serological antibody repertoires differ after seasonal influenza immunisation by each of the three vaccines and how different vaccination platforms affect the HA binding affinity and breadth of the serum antibodies that comprise the polyclonal response. METHODS: In this comparative, prospective, observational cohort study, we included female US health-care personnel (mean age 47·6 years [SD 8]) who received a single dose of RIV4, eIIV4, or ccIIV4 during the 2018-19 influenza season at Baylor Scott & White Health (Temple, TX, USA). Eligible individuals were selected based on comparable day 28 serum microneutralisation titres and similar vaccination history. Laboratory investigators were blinded to assignment until testing was completed. The preplanned exploratory endpoints were assessed by deconvoluting the serological repertoire specific to A/Singapore/INFIMH-16-0019/2016 (H3N2) HA before (day 0) and after (day 28) immunisation using bottom-up liquid chromatography-mass spectrometry proteomics (referred to as Ig-Seq) and natively paired variable heavy chain-variable light chain high-throughput B-cell receptor sequencing (referred to as BCR-Seq). Features of the antigen-specific serological repertoire at day 0 and day 28 for the three vaccine groups were compared. Antibodies identified with high confidence in sera were recombinantly expressed and characterised in depth to determine the binding affinity and breadth to time-ordered H3 HA proteins. FINDINGS: During September and October of the 2018-19 influenza season, 15 individuals were recruited and assigned to receive RIV4 (n=5), eIIV4 (n=5), or ccIIV4 (n=5). For all three cohorts, the serum antibody repertoire was dominated by back-boosted antibody lineages (median 98% [95% CI 88-99]) that were present in the serum before vaccination. Although vaccine platform-dependent differences were not evident in the repertoire diversity, somatic hypermutation, or heavy chain complementarity determining region 3 biochemical features, antibodies boosted by RIV4 showed substantially higher binding affinity to the vaccine H3/HA (median half-maximal effective concentration [EC50] to A/Singapore/INFIMH-16-0019/2016 HA: 0·037 μg/mL [95% CI 0·012-0·12] for RIV4; 4·43 μg/mL [0·030-100·0] for eIIV4; and 18·50 μg/mL [0·99-100·0] μg/mL for ccIIV4) and also the HAs from contemporary H3N2 strains than did those elicited by eIIV4 or ccIIV4 (median EC50 to A/Texas/50/2012 HA: 0·037 μg/mL [0·017-0·32] for RIV4; 1·10 μg/mL [0·045-100] for eIIV4; and 12·6 μg/mL [1·8-100] for ccIIV4). Comparison of B-cell receptor sequencing repertoires on day 7 showed that eIIV4 increased the median frequency of canonical egg glycan-targeting B cells (0·20% [95% CI 0·067-0·37] for eIIV4; 0·058% [0·050-0·11] for RIV4; and 0·035% [0-0·062] for ccIIV4), whereas RIV4 vaccination decreased the median frequency of B-cell receptors displaying stereotypical features associated with membrane proximal anchor-targeting antibodies (0·062% [95% CI 0-0·084] for RIV4; 0·12% [0·066-0·16] for eIIV4; and 0·18% [0·016-0·20] for ccIIV4). In exploratory analysis, we characterised the structure of a highly abundant monoclonal antibody that binds to both group 1 and 2 HAs and recognises the HA trimer interface, despite its sequence resembling the stereotypical sequence motif found in membrane-proximal anchor binding antibodies. INTERPRETATION: Although all three licensed seasonal influenza vaccines elicit serological antibody repertoires with indistinguishable features shaped by heavy imprinting, the RIV4 vaccine selectively boosts higher affinity monoclonal antibodies to contemporary strains and elicits greater serum binding potency and breadth, possibly as a consequence of the multivalent structural features of the HA immunogen in this vaccine formulation. Collectively, our findings show advantages of RIV4 vaccines and more generally highlight the benefits of multivalent HA immunogens in promoting higher affinity serum antibody responses. FUNDING: Centers for Disease Control and Prevention, National Institutes of Health, and Bill & Melinda Gates Foundation.

OBJECTIVES: To describe patterns of medication for opioid use disorder (MOUD) during pregnancies in the opioid use disorder (OUD) cohort of MAT-LINK, a sentinel surveillance network of pregnancies at US clinical sites. METHODS: Seven clinical sites providing care for pregnant people with OUD collected electronic health record data. Pregnancies were included in this analysis if (1) the pregnancy outcome occurred between January 2014 and August 2021, (2) the person had OUD, and (3) there was any electronic health record-documented MOUD during pregnancy. Analyses describing MOUD type, demographic characteristics, and timing during pregnancy were performed. RESULTS: Among 3911 pregnancies with any documented MOUD, more than 90% of pregnancies with methadone were to publicly insured people, which was greater than percentages for pregnancies with other MOUD. Buprenorphine with naloxone and naltrexone were two MOUD types that were increasingly common among pregnant people in recent years. In most pregnancies, prenatal care and MOUD were first documented in the same trimester. During the first, second, and third trimesters, there were 37%, 61%, and 91% of pregnancies with MOUD, respectively. Approximately 87% (n = 3412) had only 1 documented MOUD type, versus 2 or 3 types. However, discontinuity in MOUD across trimesters was still observed. CONCLUSIONS: In MAT-LINK's OUD cohort, the overall frequency of MOUD improved over the course of pregnancy. Contextual factors, such as insurance status and year of pregnancy outcome, might influence MOUD type. Prenatal care and MOUD might be facilitators for one another; however, there are still opportunities to improve early linkage and continuous access to both prenatal care and MOUD during pregnancy.

Hepatitis B (HepB) vaccines have demonstrated safety, immunogenicity, and efficacy during the past 4 decades (1,2). The Advisory Committee on Immunization Practices recommends universal HepB vaccination for adults aged 19-59 years, including pregnant persons, and adults aged ≥60 years with risk factors for hepatitis B. Adults aged ≥60 years without known risk factors for hepatitis B may also receive HepB vaccines (2).

Studies in SIV-infected macaques show that the virus reservoir is particularly refractory to conventional suppressive antiretroviral therapy (ART). We posit that optimized ART regimens designed to have robust penetration in tissue reservoirs and long-lasting antiviral activity may be advantageous for HIV or SIV remission. Here we treat macaques infected with RT-SHIV with oral emtricitabine/tenofovir alafenamide and long-acting cabotegravir/rilpivirine without (n = 4) or with (n = 4) the immune activator vesatolimod after the initial onset of viremia. We document full suppression in all animals during treatment (4-12 months) and no virus rebound after treatment discontinuation (1.5-2 years of follow up) despite CD8 + T cell depletion. We show efficient multidrug penetration in virus reservoirs and persisting rilpivirine in plasma for 2 years after the last dose. Our results document a type of virus remission that is achieved through early treatment initiation and provision of ultra long-lasting antiviral activity that persists after treatment cessation.

INTRODUCTION: As perinatal drug overdoses continue to rise, reliable approaches are needed to monitor overdose trends during pregnancy and postpartum. This analysis aimed to determine the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ICD-9/10-CM codes for drug overdose events among people in the MATernaL and Infant clinical NetworK (MAT-LINK) with medication for opioid use disorder (MOUD) during pregnancy. METHODS: People included in this analysis had electronic health record (EHR) documentation of MOUD and a known pregnancy outcome from January 1, 2014 through August 31, 2021. Data were analyzed during pregnancy through one year postpartum. CDC's drug overdose case definitions were used to categorize overdose based on ICD-9/10-CM codes. These codes were compared to abstracted EHR data of any drug overdose. Analyses were conducted between May 2023 and May 2024. RESULTS: Among 3,911 pregnancies with EHR-documented MOUD, the sensitivity of ICD-9/10-CM codes for capturing drug overdose during pregnancy was 32.7%, while specificity was 98.5%, PPV was 23.4%, and NPV was 99.0%. The sensitivity of ICD-9/10-CM codes for capturing drug overdose postpartum was 30.9%, while specificity was 98.4%, PPV was 25.9%, and NPV was 98.8%. CONCLUSIONS: The sensitivity and PPV of ICD-9/10-CM codes for capturing drug overdose compared to abstracted EHR data during the perinatal period was low in this cohort of people with MOUD during pregnancy, though the specificity and NPV were high. Incorporating other data from EHRs and outside the healthcare system might provide more comprehensive insights on nonfatal drug overdose in this population.

BACKGROUND: Population-based incidence data on young-adult-onset type 1 diabetes and type 2 diabetes are limited. We aimed to examine secular trends in the incidence of diagnosed type 1 diabetes and type 2 diabetes with an age of onset between 15 and 39 years. METHODS: In this multicountry aggregate data analysis, we assembled eight administrative datasets from high-income jurisdictions and countries (Australia, Denmark, Finland, Hungary, Japan, Scotland, South Korea, and Spain [Catalonia]) that had appropriate data available from an international diabetes consortium (GLOBODIAB) describing incidence by diabetes type among people aged 15-39 years from 2000 to 2020. We modelled type 1 diabetes and type 2 diabetes incidence rates using Poisson regression including age and calendar time by sex. FINDINGS: During the years 2000-20, there were 349 591 incident diabetes (both types) cases from 346 million person-years of follow-up among people aged 15-39 years. Over time, there was no statistically significant change in the incidence of type 1 diabetes in Hungary and Japan. The incidence of type 1 diabetes significantly increased in Australia, Denmark, Finland, Scotland, South Korea, and Spain, with annual changes ranging from 0·5% to 6·0%. The incidence of type 2 diabetes significantly increased in four of eight jurisdictions (Denmark, Finland, Japan, and South Korea), with annual increases from 2·0% to 8·5%. The magnitude of increase in incidence of type 2 diabetes was greater in Asian than non-Asian jurisdictions. There was no statistically significant change in type 2 diabetes incidence in Australia and Hungary. The incidence of type 2 diabetes significantly decreased in Scotland and Spain, with annual changes of -0·7% and -1·5%, respectively. INTERPRETATION: There is variability in the trajectory of the incidence of young-adult-onset type 2 diabetes among high-income countries or jurisdictions, with a greater evidence of increase in Asian than non-Asian countries. Evolving trends in the incidence of type 1 and type 2 diabetes in young adults call for the ongoing surveillance of diabetes incidence and a greater research focus on this population. FUNDING: US Centers for Disease Control and Prevention, Diabetes Australia Research Programme, and Victoria State Government Operational Infrastructure Support Programme.

IMPORTANCE: Seasonal influenza is associated with substantial disease burden. The relationship between census tract-based social vulnerability and clinical outcomes among patients with influenza remains unknown. OBJECTIVE: To characterize associations between social vulnerability and outcomes among patients hospitalized with influenza and to evaluate seasonal influenza vaccine and influenza antiviral utilization patterns across levels of social vulnerability. DESIGN, SETTING, AND PARTICIPANTS: This retrospective repeated cross-sectional study was conducted among adults with laboratory-confirmed influenza-associated hospitalizations from the 2014 to 2015 through the 2018 to 2019 influenza seasons. Data were from a population-based surveillance network of counties within 13 states. Data analysis was conducted in December 2023. EXPOSURE: Census tract-based social vulnerability. MAIN OUTCOMES AND MEASURES: Associations between census tract-based social vulnerability and influenza outcomes (intensive care unit admission, invasive mechanical ventilation and/or extracorporeal membrane oxygenation support, and 30-day mortality) were estimated using modified Poisson regression as adjusted prevalence ratios. Seasonal influenza vaccine and influenza antiviral utilization were also characterized across levels of social vulnerability. RESULTS: Among 57 964 sampled cases, the median (IQR) age was 71 (58-82) years; 55.5% (95% CI, 51.5%-56.0%) were female; 5.2% (5.0%-5.4%) were Asian or Pacific Islander, 18.3% (95% CI, 18.0%-18.6%) were Black or African American, and 64.6% (95% CI, 64.2%-65.0%) were White; and 6.6% (95% CI, 6.4%-68%) were Hispanic or Latino and 74.7% (95% CI, 74.3%-75.0%) were non-Hispanic or Latino. High social vulnerability was associated with higher prevalence of invasive mechanical ventilation and/or extracorporeal membrane oxygenation support (931 of 13 563 unweighted cases; adjusted prevalence ratio [aPR], 1.25 [95% CI, 1.13-1.39]), primarily due to socioeconomic status (790 of 11 255; aPR, 1.31 [95% CI, 1.17-1.47]) and household composition and disability (773 of 11 256; aPR, 1.20 [95% CI, 1.09-1.32]). Vaccination status, presence of underlying medical conditions, and respiratory symptoms partially mediated all significant associations. As social vulnerability increased, the proportion of patients receiving seasonal influenza vaccination declined (-19.4% relative change across quartiles; P < .001) as did the proportion vaccinated by October 31 (-6.8%; P < .001). No differences based on social vulnerability were found in in-hospital antiviral receipt, but early in-hospital antiviral initiation (-1.0%; P = .01) and prehospital antiviral receipt (-17.3%; P < .001) declined as social vulnerability increased. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, social vulnerability was associated with a modestly increased prevalence of invasive mechanical ventilation and/or extracorporeal membrane oxygenation support among patients hospitalized with influenza. Contributing factors may have included worsened baseline respiratory health and reduced receipt of influenza prevention and prehospital or early in-hospital treatment interventions among persons residing in low socioeconomic areas.

IMPORTANCE: Multiplex molecular syndromic panels for diagnosis of urinary tract infection (UTI) lack clinical data supporting their use in routine clinical care. They also have the potential to exacerbate inappropriate antibiotic prescribing. OBJECTIVE: To describe the frequency of unspecified multiplex testing in administrative claims with a primary diagnosis of UTI in the Medicare population over time, to assess costs, and to characterize the health care professionals (eg, clinicians, laboratories, physician assistants, and nurse practitioners) and patient populations using these tests. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used Centers for Medicare & Medicaid Services (CMS) claims data for Medicare beneficiaries. The study included older community-dwelling adults and nursing home residents with fee-for-service Medicare Part A and Part B benefits from January 1, 2016, to December 31, 2023. MAIN OUTCOMES AND MEASURES: Multiplex syndromic panels were identified using carrier claims (ie, claims for clinician office or laboratory services). The annual rate of claims was measured for multiplex syndromic panels with a primary diagnosis of UTI per 10 000 eligible Medicare beneficiaries. The performing and referring specialties of health care professionals listed on claims of interest and the proportion of claims that occurred among beneficiaries residing in a nursing home were described. RESULTS: Between 31 110 656 and 36 175 559 Medicare beneficiaries with fee-for-service coverage annually (2016-2023) were included in this study. In this period, 1 679 328 claims for UTI multiplex testing were identified. The median age of beneficiaries was 77 (IQR, 70-84) years; 34% of claims were from male beneficiaries and 66% were from female beneficiaries. From 2016 to 2023, the observed rate of UTI multiplex testing increased from 2.4 to 148.1 claims per 10 000 fee-for-service beneficiaries annually, and the proportion of claims that occurred among beneficiaries residing in a nursing home ranged from 1% in 2016 to 12% in 2020. In addition to laboratories or pathologists, urology was the most common clinician specialty conducting this testing. The CMS-assigned referring clinician specialty was most frequently urology or advanced practice clinician for claims among community-dwelling beneficiaries compared with internal medicine or family medicine for claims among nursing home residents. In 2023, the median cost of a multiplex test in the US was $585 (IQR, $516-$695 for Q1-Q3), which was more than 70 times higher than the median cost of $8 for a urine culture (IQR, $8-$16 for Q1-Q3). CONCLUSIONS AND RELEVANCE: This cohort study of Medicare beneficiaries with fee-for-service coverage from 2016 to 2023 found increasing use of emerging multiplex testing for UTI coupled with high costs to the Medicare program. Monitoring and research are needed to determine the effects of multiplex testing on antimicrobial use and whether there are clinical situations in which this testing may benefit patients.

BACKGROUND: On 20 September 2022, the Ugandan Ministry of Health declared an outbreak of Ebola disease caused by Sudan ebolavirus. METHODS: From 6 October 2022 to 10 January 2023, Centers for Disease Control and Prevention (CDC) staff conducted public health assessments at five US ports of entry for travellers identified as having been in Uganda in the past 21 days. CDC also recommended that state, local and territorial health departments ('health departments') conduct post-arrival monitoring of these travellers. CDC provided traveller contact information, daily to 58 health departments, and collected health department data regarding monitoring outcomes. RESULTS: Among 11 583 travellers screened, 132 (1%) required additional assessment due to potential exposures or symptoms of concern. Fifty-three (91%) health departments reported receiving traveller data from CDC for 10 114 (87%) travellers, of whom 8499 (84%) were contacted for monitoring, 1547 (15%) could not be contacted and 68 (1%) had no reported outcomes. No travellers with high-risk exposures or Ebola disease were identified. CONCLUSION: Entry risk assessment and post-arrival monitoring of travellers are resource-intensive activities that had low demonstrated yield during this and previous outbreaks. The efficiency of future responses could be improved by incorporating an assessment of risk of importation of disease, accounting for individual travellers' potential for exposure, and expanded use of methods that reduce burden to federal agencies, health departments, and travellers.

Annually, tens of thousands of U.S. children and adolescents are hospitalized with seasonal influenza virus infection. Both influenza vaccination and early initiation of antiviral treatment can reduce complications of influenza. Using data from two U.S. influenza surveillance networks for children and adolescents aged <18 years with medically attended, laboratory-confirmed influenza for whom antiviral treatment is recommended, the percentage who received treatment was calculated. Trends in antiviral treatment of children and adolescents hospitalized with influenza from the 2017-18 to the 2023-2024 influenza seasons were also examined. Since 2017-18, when 70%-86% of hospitalized children and adolescents with influenza received antiviral treatment, the proportion receiving treatment notably declined. Among children and adolescents with influenza during the 2023-24 season, 52%-59% of those hospitalized received antiviral treatment. During the 2023-24 season, 31% of those at higher risk for influenza complications seen in the outpatient setting in one network were prescribed antiviral treatment. These findings demonstrate that influenza antiviral treatment is underutilized among children and adolescents who could benefit from treatment. All hospitalized children and adolescents, and those at higher risk for influenza complications in the outpatient setting, should receive antiviral treatment as soon as possible for suspected or confirmed influenza.

INTRODUCTION: As part of a laboratory strengthening program in Malawi to achieve and maintain International Organization for Standardization (ISO) 15189 accreditation, we intended to mentor selected HIV molecular laboratories to achieve this accreditation. Due to the COVID-19 pandemic, mentorship pivoted to a hybrid model using an Internet-based approach and on-site mentorships. We describe the implementation of this strategy, successes, and challenges. METHODS: We conducted weekly, 1-hour virtual mentorship sessions for the 5 initial laboratories (cohort 1) selected based on their Stepwise Laboratory Quality Improvement Process Towards Accreditation (SLIPTA) performance score of 3 or more stars. Laboratories presented updates and supporting documents electronically, and trainings were conducted virtually. In September 2020, when travel restrictions were relaxed, we initiated hybrid mentorships and audits for cohort 1 laboratories. The same hybrid approach was used to mentor 4 additional laboratories in cohort 2. We performed descriptive analysis, and the Wilcoxon signed-rank test was used to compare the training pre-and post-test scores. RESULTS: Between March 2020 and May 2023, the team completed a total of 54 virtual mentorship sessions and 20 on-site visits across 9 laboratories. Overall, the team conducted 8 training sessions for 35 laboratory quality officers. Median score improvement (pre-test vs. post-test scores) was observed across individual trainings and across cohorts (P<.01). At the end of cohort 1, 4 of 5 (80%) laboratories were accredited. One laboratory that did not reach accreditation joined cohort 2. At the end of the mentoring period, all 5 cohort 2 laboratories were accredited. CONCLUSIONS: We demonstrated that using a hybrid mentorship model for accreditation was a successful strategy during the COVID-19 pandemic. For the first time in Malawi, this strategy resulted in accrediting 9 of the 10 HIV molecular laboratories in 3 years at a reduced cost. Continuous mentorship is key in the maintenance of accreditation.