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.

International guidelines are available for the assessment and improvement of antimicrobial stewardship (AMS) programmes: an important strategy to address the escalating global antimicrobial resistance problem. However, existing AMS assessment tools lack contextual specificity for resource-limited settings, leading to limited applicability in Asia. This project aimed to identify relevant themes from current guidance documents to help develop a context-specific assessment tool that can be applied by healthcare facilities (HCFs) to improve local implementation.We performed a sequential approach of a scoping review to identify relevant assessment themes for Asia and an expert survey for getting feedback on the relevance of assessment stems developed from the scoping review. We reviewed English-language published documents discussing AMS implementation or assessment at HCFs globally and in Asia. Themes were derived through content analysis and classified following the predefined context dimensions to develop assessment stems, defined as containing one identified determinant that may influence implementation outcomes. The survey consisting of identified assessment stems was reviewed by 20 locally identified experts in Asia who rated the level of relevance of these stems in AMS implementation in the region.National leadership, training and technical support, and policy and guidance were the most commonly identified themes among 100 themes identified from 73 reviewed documents. From these themes, we developed 131 assessment stems for the expert survey. Of the 131 assessment stems, 117 (89%) were considered relevant for AMS implementation in Asia by at least 80% of respondents. These stems were included in the process of developing a global AMS assessment tool to support HCFs to improve their programmes.In conclusion, national leadership and support represent a distinct and important aspect affecting AMS implementation in HCFs in Asia. The identified assessment themes have substantial value for the formulation of locally relevant implementation strategies tailored to the Asian context.

HIV prevention efforts have traditionally focused on urban areas, yet about one-fourth of new HIV diagnoses in the U.S. are in non-urban areas. This study explored rural and urban differences in perceived HIV risk; perceived HIV stigma; and pre-exposure prophylaxis (PrEP) awareness, attitudes, beliefs, communication behaviors, and use to inform the development of communication messages to promote informed decision-making among available HIV prevention options, including PrEP. We conducted interviews, preceded by a brief survey, with 255 adults in 5 rural and 6 urban locations throughout the U.S. with high HIV burden. Participants from rural areas more frequently described their risk of getting HIV as low compared with those from urban areas, although partly due to differences in gender/sexual identity and sexual risk. Participants from rural areas more frequently reported perceived stigma around getting tested for HIV, taking PrEP to prevent HIV, or having HIV and less frequently reported having heard of PrEP and having a healthcare provider talk with them about PrEP compared with those from urban areas. No participants from rural areas reported using PrEP, although 48% of those with HIV-negative or unknown status were at substantial risk based on reported risk factors. Our findings highlight notable differences in perceived HIV risk; perceived HIV stigma; and PrEP awareness, attitudes, beliefs, communication behaviors, and use between individuals residing in rural and urban areas, suggesting that HIV prevention messaging needs to be tailored for rural audiences to support receptivity.

Nail polishes contain over a dozen chemical compounds, including chemicals that can cause adverse reproductive outcomes and pose a risk to the high proportion of nail salon workers who are women of childbearing age. Consumer demand has resulted in a shift toward more natural products, with manufacturers attempting to remove harmful ingredients (n-free products). Many products that claim to have eliminated toluene, formaldehyde, and dibutyl phthalate (DBP) are labeled as "3-free"; however, studies have found these products often contain higher concentrations of toluene and DBP compared to products with no such claims. Products used only at salons are not required to list ingredients, leading to uncertainties as to the exact chemical composition and potential exposures. A better understanding of chemical exposures associated with nail polish products is necessary to understand potential worker exposures and develop effective control options. This study evaluated chemical exposures generated while painting nails with 20 n-free polishes using real-time and time-integrated air sampling. Total volatile organic compounds (TVOCs, PID, ION Science Inc.) and 22 individual compounds (FTIR, Gasmet Technologies) were measured in the breathing zone of the manicurist while two coats of polish were applied to artificial nails on a manikin in an exposure chamber and for 2 hr afterwards. Formaldehyde and toluene were measured in all polishes using the real-time FTIR, despite all claiming to be 3-free. Normalized geometric mean (GM) formaldehyde exposures from the FTIR ranged from 0.021 to 0.273 ppm/g, GM toluene exposures ranged from 0.068 to 0.534 ppm/g, and GM benzene exposures ranged from 0.076 to 0.752 ppm/g. Notably, formaldehyde, toluene, and benzene exposures did not significantly differ between different products. Neither DBP nor triphenyl phosphate (TPhP) was detected in any of the polishes. This study highlights that despite industry claims, n-free polishes may still contain chemicals associated with negative health effects and that more studies are necessary to understand the true chemical exposures of nail salon workers.

BACKGROUND: In 2023, the United States Food and Drug Administration revised its blood donor eligibility policy for men who have sex with men (MSM) from a 3-month deferral to individual assessment. Human Immunodeficiency Virus (HIV) pre-exposure prophylaxis (PrEP) use remains a reason for deferral, and nondisclosure is a concern. STUDY DESIGN AND METHODS: In a cross-sectional study of sexually active MSM from 8 U.S. cities who were interested in future blood donation, we assessed the performance of an enzyme-linked immunosorbent assay for detecting tenofovir (TFV) in whole blood (WB) and plasma and the correlation with self-reported PrEP use. RESULTS: Of 1548 individuals, 48% reported oral PrEP use. The WB assay identified 95% of PrEP users, while the plasma assay detected 88%. The WB assay performed well up to 14 days after the last reported dose. Receiver operating characteristics curve analysis showed an area under the curve of 0.96 (95% confidence interval [CI]: 0.95-0.97) using WB and 0.88 (95% CI: 0.86-0.90) using plasma. Specificity was 80% for WB and 66% for plasma. Detection rates for TFV disoproxil fumarate/emtricitabine (FTC) formulations were 99% in WB and 98% in plasma, compared to 93% and 86% for the TFV alafenamide/FTC formulation. DISCUSSION: High concordance between self-reported oral PrEP use and TFV detection was observed among PrEP users, suggesting the potential utility of WB as a biomatrix for TFV detection to support screening strategies. Given the expanded eligibility for MSM, who may be PrEP users, to donate blood, further examination of undisclosed PrEP use is important.

BACKGROUND: Patients hospitalised with influenza have heterogeneous clinical presentations and disease severity, which may complicate epidemiologic study design or interpretation. We applied latent class analysis to identify clinically distinct subgroups of adults hospitalised with influenza. METHODS: We analysed cross-sectional study data on adults (≥18 years) hospitalised with laboratory-confirmed influenza from the population-based U.S. Influenza Hospitalization Surveillance Network (FluSurv-NET) including 13 states during 2017-2018 and 2018-2019 influenza seasons (October 1 through April 30). Adults were included if they were residents of the FluSurv-NET catchment area, hospitalised with laboratory-confirmed influenza during these two seasons, and had both the main case report form and the supplemental disease severity case report form completed. We constructed a latent class model to identify subgroups from multiple observed variables including baseline characteristics (age and comorbidities) and clinical course (symptoms at admission, respiratory support requirement, and development of new complications and exacerbations of underlying conditions). FINDINGS: Among the 43,811 influenza-associated hospitalizations reported during the 2017-2018 and 2018-2019 influenza seasons, 15,873 (36.2%) were included in our analytic population: among them, 7069 (44.5%) were male and 8804 (55.5%) were female. We identified five subgroups. Subgroup A included persons of all ages with few comorbidities and 87.9% (255/290) of pregnant women. Subgroup B included older adults with comorbidities (cardiovascular disease (79.7% [3650/4581]) and diabetes (50.6% [2320/4581])). Almost all patients in subgroups C and D had asthma or chronic lung disease and high proportions with exacerbations of underlying conditions (59.7% [889/1489] and 65.1% [2274/3496], respectively). Subgroup E had the highest proportion with new complications (90.3% [1383/1531]). Subgroups D and E had the highest proportions with severe disease indicators: 21.0% (733/3496) and 50.4% (771/1531) required ICU admission, 7.2% (253/3496) and 28.0% (428/1531) required invasive mechanical ventilation, and 3.3% (116/3496) and 11.4% (174/1531) died in-hospital, respectively. INTERPRETATION: The five identified subgroups of adults hospitalised with influenza had varying distributions of age, comorbid conditions, and clinical courses characterized by new complications versus exacerbations of existing conditions. Stratifying by these subgroups may strengthen analyses that assess the impact of influenza vaccination and antiviral treatment on risk of severe disease. Limitations included that results were based on a convenience sample within FluSurv-NET sites and were likely not representative of all adults hospitalised with influenza in the United States. Influenza testing was also clinician-driven, likely leading to under-ascertainment. FUNDING: Centers for Disease Control and Prevention.

PURPOSE: Per- and polyfluoroalkyl substances (PFAS) are associated with multiple health effects including pregnancy-induced hypertension and pre-eclampsia, increased serum hepatic enzymes, increased in serum lipids, decreased antibody response to vaccines, and decreased birth weight. Millions of US workers are exposed to PFAS at their workplaces. Our objective was to estimate the serum levels of the five PFAS that are most frequently detected in the US general population(perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorodecanoic acid (PFDA), and perfluorononanoic acid (PFNA)) among US adult workers. METHODS: Participants were 4476 workers aged ≥ 20 years with PFAS analyte results available who participated in the National Health and Nutrition Examination Survey (NHANES), 2005-2014. Geometric mean serum levels of PFAS (ng/mL) were obtained across industry and occupation groups using the PFAS subsample weight in SAS-callable SUDAAN V11. RESULTS: Among 21 industry groups, the highest geometric mean PFAS levels (ng/mL) were observed in Construction (PFOS = 12.61 ng/mL, PFOA = 3.76, PFHxS = 2.10, PFNA = 1.23, and PFDA = 0.33), followed by Utilities (PFOS = 12.46), and Real Estate/Rental/Leasing (PFOS = 12.15). The lowest geometric mean PFAS levels were seen in Private Households (PFOS = 6.34, PFOA = 2.12, PFHxS=0.75, PFNA = 0.86, and PFDA = 0.25). Among 22 occupation groups, the highest geometric mean PFAS levels were observed in Life/Physical/Social Science occupations (PFOS = 13.19, PFOA = 3.54, PFHxS= 1.69, PFNA = 1.23, and PFDA = 0.33), followed by Installation/Maintenance/Repair occupations (PFOS = 12.75), and Construction/Extraction occupations (PFOS = 12.15). The lowest geometric mean PFAS levels were found in Personal Care/Service occupations (PFOS = 7.25, PFOA = 2.43, PFHxS = 1.07, PFNA = 0.94, and PFDA = 0.25). CONCLUSIONS: Some industry and occupation groups had higher geometric mean levels of PFAS in serum compared to others. Further investigation of these industries and occupations may result in a better understanding of the sources and degree of occupational exposure to PFAS.

BACKGROUND: This report represents a collaborative effort by the major cancer surveillance organizations to present the definitive US statistics for cancer incidence and mortality. METHODS: Cancer incidence data were obtained from population-based cancer registries funded by the Centers for Disease Control and Prevention and the National Cancer Institute and compiled by the North American Association of Central Cancer Registries. Cancer death data were obtained from the National Center for Health Statistics' National Vital Statistics System. Statistics are reported by cancer type, sex, race and ethnicity, and age. The potential impact of the coronavirus disease 2019 (COVID-19) pandemic on incidence was assessed by using state-level changes compared with previous years, the stringency of COVID-19 policy restrictions, the magnitude of COVID-19 death rates, and changes in the use of mammography. RESULTS: Overall cancer incidence rates per 100,000 were 500 among males and 437 among females. Excluding 2020, cancer incidence rates remained stable (2013-2021) among males and increased 0.3% per year on average (2003-2021) among females. The overall cancer death rate per 100,000 was 173 among males and 126 among females. Cancer death rates decreased by 1.5% per year (2018-2022), slowing from a previous 2.1% decline. Cancer incidence in 2020 declined from prepandemic levels for all demographic groups examined. However, the magnitude of decline was not strongly associated with the study's proxies for health care capacity, health care access, or COVID-19 policies. CONCLUSIONS: Overall cancer mortality declined over 20 years, even during the COVID-19 pandemic. Disruptions in health care use early in the pandemic resulted in incidence declines in 2020, but 2021 incidence returned to prepandemic levels.

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.

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.

INTRODUCTION: Varicella-zoster virus (VZV) testing is increasingly needed for assessing immunity and diagnosis in the varicella vaccination era. VZV-specific immunoglobulin G (IgG) is recommended when assessing immunity; real-time polymerase chain reaction (PCR) is recommended for varicella or herpes zoster diagnosis. The study objective was to describe VZV serologic and virologic testing in U.S. clinical practice. METHODS: Patients with serologic (IgG, IgM) or virologic (PCR, culture) VZV testing were identified in five administrative data sources (∼11-100 million enrollees; 2016-2023). Descriptive analyses were used to examine VZV testing frequency, patient characteristics, and rates by test type. The top 20 diagnostic codes associated with VZV test type were used as a proxy for reason for testing. RESULTS: Across data sources, the highest proportion of VZV testing was for IgG (43%-92%); most was in females (79%-82%) and those aged 20-39 years (62%-70%). Rates of serologic testing were 50-60/10,000 persons. Frequency of VZV virologic testing was considerably lower; PCR testing rates were ∼1/10,000 persons. Diagnostic codes associated with IgG or virologic testing were primarily categorized as routine care or acute illness, respectively. IgM testing was up to 11% of tests, despite not being recommended for screening or diagnostic purposes. CONCLUSIONS: VZV serologic testing rates were 50-60 times higher than PCR. Serologic testing was more common among females and young adults, likely due to screening. Most VZV testing appeared relevant to clinical management; however, inappropriate IgM testing was identified. Appropriate testing is important to guide clinical and public health management for varicella and herpes zoster.

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.

This study investigated the potential pulmonary toxicity of polycarbonate (PC) emissions from fused filament fabrication (FFF) three-dimensional printing (3DP) via inhalation in Sprague Dawley rats. Previously, our results demonstrated no significant pulmonary effects following exposure to a 0.5 mg/m(3) PC. A new exposure apparatus was developed that exposed animals at a concentration of 2.5 mg/m(3). Sixty rats were randomized into control (filtered air) and exposure groups (n = 30/group). Each group was further divided into five subgroups (n = 6/subgroup) with exposure durations of 1, 4, 8, 15, or 30 days (4 hr/day, 4 days/week). Following a 24-hr post-exposure period, body weight was measured, and blood samples were collected for hematological and biochemical analysis. Bronchoalveolar lavage fluid (BALF) was obtained from the right lung for cytology. The left lung and head/nasal tissues were preserved for histopathological evaluation. Lung deposition was estimated using the Multiple-Path Particle Dosimetry model, electron microscopy, and enhanced darkfield microscopy. In addition, filter samples were collected to measure bisphenol A. Exposure resulted in an estimated deposition of 0.28 µg/day within the alveoli and small airways. Microscopy indicated limited evidence of macrophage uptake. No significant changes were observed in BALF cell counts, lactate dehydrogenase activity, or hematological parameters. BALF levels of tissue inhibitor of metalloproteinases-1 and protein were elevated in the 30-day exposure group, although histopathology revealed no exposure-related changes in the lungs. In conclusion, this study found no marked pulmonary inflammation or toxicity in rats exposed to 2.5 mg/m(3) of PC 3D printing emissions for up to 30 days (4 hr/day).

Per- and polyfluoroalkyl substances (PFAS) have been associated with increased risk of hypertensive disorders of pregnancy, but whether PFAS influence blood pressure (BP) trajectories among normotensive pregnant women is unknown. We examined associations between PFAS mixtures and BP trajectories during pregnancy among normotensive women. PFAS concentrations, including perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), and perfluorodecanoate (PFDA), were measured in plasma collected at ∼28 gestational weeks among pregnant women enrolled in the New Hampshire Birth Cohort Study (2009-2018). Systolic BP (SBP) and diastolic BP (DBP) were abstracted from pregnancy medical records. We identified BP trajectories using latent class trajectory modeling and evaluated associations between PFAS mixtures and BP trajectories using probit Bayesian kernel machine regression and multinomial quantile g-computation. We used linear mixed models to examine individual PFAS and BP changes during the third trimester. Models were adjusted for sociodemographic, lifestyle, and reproductive factors, and gestational week of blood sample collection. During late pregnancy, plasma PFOS was associated with greater increases in SBP and PFHxS was associated with greater increases in DBP. Over the third trimester, each doubling in plasma PFOS was associated with 0.07 mmHg (95% CI: -0.01, 0.14) increase per week in SBP, and each doubling in plasma PFHxS was associated with 0.07 mmHg (95% CI: 0.02, 0.12) increase per week in DBP. Our study provides additional evidence suggesting that PFAS may adversely influence blood pressure even among normotensive women.

We report the results of a scoping review of the literature investigating associations between positive childhood experiences (PCEs) and selected health outcomes to identify which have the highest level of research activity based on the indexed academic literature. Yielded articles underwent title/abstract (Ti/Ab) and full text screening utilizing inclusion/exclusion criteria. The review was guided by PCE categories from the Healthy Outcomes from Positive Experiences framework: relationships, environment, engagement, and emotional growth. The initial search yielded 8,919 unduplicated articles, 759 were retained following Ti/Ab review and 220 articles were retained after full text screening describing 795 tested associations across 23 PCE types in ten outcome categories. The outcomes most commonly examined were substance misuse (305 tested associations across 93 studies), suicidal behaviors (195 tested associations across 56 studies), and depression (112 tested associations across 55 studies). Physical health outcomes were less common (14 tested associations across six studies). Of the PCE exposures, relationships represented 415 of tested associations, 236 with environment, and 114 with social engagement. A significant body of research demonstrated associations between PCEs and health outcomes. While further research is needed, available research suggests that public health efforts to promote PCEs may have impact across multiple domains.

IMPORTANCE: The natural history of C. difficile progression in nucleic acid amplification test (NAAT) positive, toxin enzyme immunoassay-negative patients remains poorly described. Better understanding risk for subsequent disease may improve prevention strategies. OBJECTIVE: Describe the natural history of C. difficile NAAT+/toxin- adults. DESIGN: A cohort of adults (≥18 years) tested for C. difficile within Duke University Health System between 15 March 2020 and 31 December 2023 were classified as NAAT-, NAAT+/toxin-, or NAAT+/toxin+ and followed up to 90 days. Three time-to-event analyses were conducted. Incidence of toxin+ episodes was assessed by initial test status (analysis 1). Treatment of NAAT+/toxin- adults was described using cumulative incidence curves (analysis 2). Rates of toxin+ episodes and severe disease were compared between treated and untreated NAAT+/toxin- adults (analysis 3). RESULTS: The cohort included 24,474 tests and 440 toxin+ episodes among 18,337 unique subjects followed for a median 71 days. NAAT+/toxin- status was associated with subsequent toxin positivity (adjusted hazard ratio, aHR 5.06, 95% CI 3.61-7.10) - especially after antibiotic receipt (aHR 15.71, 95% CI 9.85-25.06). Among 2,334 NAAT+/toxin- episodes, 33% received presumptive treatment. Just 5% of NAAT+/toxin- subjects progressed to toxin positivity. Presumptive treatment was associated with lower hazard of subsequent toxin positivity (aHR 0.12, 95% CI 0.05-0.29) but not fulminant disease (aHR 1.93, 95% CI 0.50-7.45). CONCLUSIONS AND RELEVANCE: C. difficile NAAT+/toxin- status was associated with subsequent toxin positivity, especially after antibiotic receipt, though absolute risk was low overall. Further research is needed to determine whether and for whom presumptive treatment might be beneficial.

Coronavirus disease-2019 precipitated the rapid deployment of novel therapeutics, which led to operational and logistical challenges for healthcare organizations. Four health systems participated in a qualitative study to abstract lessons learned, challenges, and promising practices from implementing neutralizing monoclonal antibody (nMAb) treatment programs. Lessons are summarized under three themes that serve as critical building blocks for health systems to rapidly deploy novel therapeutics during a pandemic: (1) clinical workflows, (2) data infrastructure and platforms, and (3) governance and policy. Health systems must be sufficiently agile to quickly scale programs and resources in times of uncertainty. Real-time monitoring of programs, policies, and processes can help support better planning and improve program effectiveness. The lessons and promising practices shared in this study can be applied by health systems for distribution of novel therapeutics beyond nMAbs and toward future pandemics and public health emergencies. © The Author(s), 2024. Published by Cambridge University Press.

INTRODUCTION: Pandemic influenza vaccine development focuses on the hemagglutinin (HA) antigen for potency and immunogenicity. Antibody responses targeting the neuraminidase (NA) antigen, or the HA stalk domain have been implicated in protection against influenza. Responses to the NA and HA-stalk domain following pandemic inactivated influenza are not well characterized in humans. MATERIAL AND METHODS: In a series of clinical trials, we determine the vaccines' NA content and demonstrate that NA inhibition (NAI) antibody responses increase in a dose-dependent manner following a 2-dose priming series with AS03-adjuvanted influenza A(H7N9) inactivated vaccine (A(H7N9) IIV). NAI antibody responses also increase with interval extension of the 2-dose priming series or following a 5-year delayed boost with a heterologous adjuvanted A(H7N9) IIV. Neither concomitant seasonal influenza vaccination given simultaneously or sequentially, nor use of heterologous A(H7N9) IIVs in the 2-dose priming series had an appreciable effect on NAI antibody responses. Anti-HA stalk antibody responses were minimal and not durable. CONCLUSIONS: We provide evidence for strategies to improve anti-neuraminidase responses which can be further standardized for pandemic preparedness. CLINICAL TRIAL REGISTRY NUMBERS: NCT03312231, NCT03318315, NCT03589807, NCT03738241.

The fundamental goal of this study was to determine the potential utility of a novel humanized Toll-like receptor-4 (hTLR-4) mouse model for future in vivo studies of nickel allergy. First, mice of both sexes and hTLR-4 expression profiles were incorporated into a Local Lymph Node Assay (LLNA) to assess skin sensitization. Next, a set of hTLR-4 hTLR-4-positive mice (female and male groups) was similarly exposed to vehicle control (VC) or 10% NiSO(4) on Days 1, 2, and 3. Mice were euthanized on Day 10, lymph node (LN) cellularity was assessed, LN and spleen cells were phenotyped, and serum was collected to quantify circulating cytokine and IgE levels. In the LLNA, hTLR-4-positive mice of both sexes exhibited enhanced responsivity to nickel. NiSO(4) (10%) had a stimulation index (SI) of 3.7 (females) and 3.8 (males) in hTLR-4-positive animals, and an SI of 0.5 (females) and 0.8 (males) in hTLR-4 hTLR-4-negative mice. In the 10d study, hTLR-4-positive mice exposed to 10% NiSO(4) exhibited increased LN cellularity (6.0× increase in females, 3.2× in males) and significantly higher concentrations of circulating IgE (4.1× increase in females, 3.4× in males). Significant increases in serum interferon (IFN)-γ, interleukin (IL)-4, and IL-5 levels were seen in female mice, while altered concentrations of IL-4 and IL-10 were detected in male mice. The results of this study ultimately demonstrate that murine expression of hTLR-4 confers enhanced susceptibility to dermal sensitization by nickel, and consequently, the hTLR-4 mouse model represents a viable approach for future studies of nickel allergy in vivo.

INTRODUCTION: The Inflation Reduction Act (IRA) eliminated cost sharing for Medicare Part D-covered vaccines but did not address the cost burden faced by Medicare beneficiaries who did not have prescription drug coverage. This study aimed to determine the characteristics of beneficiaries without prescription drug coverage and to assess the association between the receipt of a herpes zoster vaccine and prescription drug coverage status. METHODS: We used the 2019-2023 National Health Interview Survey and included Medicare beneficiaries aged 65 years and older who enrolled in both Parts A and B or a Medicare Advantage plan. Descriptive statistics were used to examine beneficiaries' characteristics. Logistic regressions were used to examine the associations between the receipt of a herpes zoster vaccine and Medicare prescription drug coverage. RESULTS: The study included 33,578 beneficiaries and 93.5 % of beneficiaries had prescription drug coverage. The prevalence of lacking prescription drug coverage was higher among beneficiaries who did not have a college degree, had family income below the poverty level, had no flu shot and well visit within the past year, and had no usual place for care. The probability of receiving a herpes zoster vaccine was higher among beneficiaries with prescription drug coverage than those without prescription coverage (45.2 % versus 25.3 %). CONCLUSIONS: Herpes zoster vaccination disparities between beneficiaries with and without prescription drug coverage existed before the IRA. Because the IRA only addresses the cost barrier facing by beneficiaries with prescription drug coverage, vaccination disparities was greater after the IRA implementation.

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.

BACKGROUND: A peri-urban outbreak of Rift Valley fever virus (RVFV) among dairy cattle from May through August 2018 in northern Tanzania was detected through testing samples from prospective livestock abortion surveillance. We sought to identify concurrent human infections, their phylogeny, and epidemiologic characteristics in a cohort of febrile patients enrolled from 2016-2019 at hospitals serving the epizootic area. METHODS: From September 2016 through May 2019, we conducted a prospective cohort study that enrolled febrile patients hospitalized at two hospitals in Moshi, Tanzania. Archived serum, plasma, or whole blood samples were retrospectively tested for RVFV by PCR. Human samples positive for RVFV were sequenced and compared to RVFV sequences obtained from cattle through a prospective livestock abortion study. Phylogenetic analysis was performed on complete RVFV genomes. RESULTS: Among 656 human participants, we detected RVFV RNA in four (0.6%), including one death with hepatic necrosis and other end-organ damage at autopsy. Humans infected with RVFV were enrolled from June through August 2018, and all resided in or near urban areas. Phylogenetic analysis of human and cattle RVFV sequences demonstrated that most clustered to lineage B, a lineage previously described in East Africa. A lineage E strain clustering with lineages in Angola was also identified in cattle. CONCLUSION: We provide evidence that an apparently small RVFV outbreak among dairy cattle in northern Tanzania was associated with concurrent severe and fatal infections among humans. Our findings highlight the unidentified scale and diversity of inter-epizootic RVFV transmission, including near and within an urban area.

Adverse childhood experiences (ACEs) are common and can impact health across the life course. Thus, it is essential for professionals in child- and family-serving roles, including pediatric and adult primary care clinicians, to understand the health implications of childhood adversity and trauma and respond appropriately. Screening for ACEs in health care settings has received attention as a potential approach to ACEs identification and response. Careful examination of the existing evidence on ACEs screening and consideration, from a clinical and ethical perspective, of the potential benefits, challenges, and harms is critical to ensuring evidence-informed practice. In this critical appraisal, we synthesize existing systematic and scoping reviews on ACEs screening, summarize recent studies on the ability of ACEs to predict health outcomes at the individual level, and provide a comprehensive overview of potential benefits, challenges, and harms of ACEs screening. We identify gaps in the existing evidence base and specify directions for future research. We also describe trauma-informed, relational care as an orientation and perspective that can help pediatric and primary care clinicians to sensitively assess for and respond to ACEs and other potentially traumatic experiences. Overall, we do not yet have sufficient evidence regarding the potential benefits, challenges, and harms of ACEs screening in health care and other settings. In the absence of this evidence, we cannot assume that screening will not cause harm and that potential benefits outweigh potential harms.

OBJECTIVE: Adverse childhood experiences (ACEs) are preventable, potentially traumatic events with lifelong negative impacts. Population-level data on ACEs among adolescents have historically relied on parent reports and excluded abuse-related ACEs. We present the self-reported prevalence of ACEs among a large population-based sample of US high school students. METHODS: Using cross-sectional, state-representative data from 16 states that included core ACE questions on their 2021 Youth Risk Behavior Survey, we estimate the prevalence of 8 individual (lifetime emotional, physical, or sexual abuse, physical neglect, witnessed intimate partner violence, household substance use, household poor mental health, incarcerated parent or guardian) and cumulative ACEs (0, 1, 2-3, ≥4) among a large population-based sample of adolescents, overall and by demographic characteristics (sex, race and ethnicity, age, sexual orientation). RESULTS: Emotional abuse (65.8%), household poor mental health (36.1%), and physical abuse (32.5%) had the highest prevalence. ACEs were very common, with 80.5% of adolescents experiencing at least 1 ACE and 22.4% experiencing ≥4 ACEs. Experiencing ≥4 ACEs was highest among adolescents who were female (27.7%), non-Hispanic multiracial (33.7%), non-Hispanic American Indian or Alaska Native (27.1%), gay or lesbian (36.5%), bisexual (42.1%), or who described their sexual identity some other way or were not sure of their sexual identity (questioning) (36.5%). CONCLUSIONS: Self-reported ACE estimates among adolescents exceed previously published parent-reported estimates. ACEs are not equally distributed, with important differences in individual and cumulative ACEs by demographic characteristics. Collecting ACE data directly from adolescents at the state level provides actionable data for prevention and mitigation.

BACKGROUND: Nontuberculous mycobacteria (NTM) cause pulmonary and extrapulmonary infections. Although isolation of NTM from clinical specimens has increased nationally, few studies delineated the molecular characteristics of extrapulmonary NTM. METHODS: Extrapulmonary isolates were collected by four Emerging Infections Program sites from October 2019 to March 2020 and underwent laboratory characterization, including matrix-assisted laser desorption ionization-time of flight mass spectrometry, Sanger DNA sequencing, and whole genome sequencing. Bioinformatics analyses were employed to identify species, sequence types (STs), antimicrobial resistance (AR), and virulence genes; isolates were further characterized by phylogenetic analyses. RESULTS: Among 45 isolates, the predominant species were Mycobacterium avium (n=20, 44%), Mycobacterium chelonae (n=7, 16%), and Mycobacterium fortuitum (n=6, 13%). The collection represented 31 STs across 10 species; the most common ST was ST11 (M. avium, n=7). Mycobacterium fortuitum and Mycobacterium abscessus isolates harbored multiple genes conferring resistance to aminoglycosides, beta-lactams, and macrolides. No known AR mutations were detected in rpoB, 16S, or 23S rRNAs. Slow-growing NTM species harbored multiple virulence genes including type-VII secretion components, adhesion factors, and phospholipase C. CONCLUSION: Continued active laboratory- and population-based surveillance will further inform the prevalence of NTM species and STs, monitor emerging clones, and allow AR characterization.

Among adults, COVID-19 hospitalization rates increase with age. Data from the COVID-19-Associated Hospitalization Surveillance Network were analyzed to estimate population-based COVID-19-associated hospitalization rates during October 2023-April 2024 and identify demographic and clinical characteristics of adults aged ≥18 years hospitalized with COVID-19. Adults aged ≥65 years accounted for 70% of all adult COVID-19-associated hospitalizations, and their COVID-19-associated hospitalization rates were higher than those among younger adult age groups. Cumulative rates of COVID-19-associated hospitalization during October 2023-April 2024 were the lowest for all adult age groups during an October-April surveillance period since 2020-2021. However, hospitalization rates among all adults aged ≥75 years approached one COVID-19-associated hospitalization for every 100 persons. Among adults hospitalized with COVID-19, 88.1% had not received the 2023-2024 formula COVID-19 vaccine before hospitalization, 80.0% had multiple underlying medical conditions, and 16.6% were residents of long-term care facilities (LTCFs). Guidance for adults at high risk for severe COVID-19 illness, including adults aged ≥65 years and residents of LTCFs, should continue to focus on adopting measures to reduce risk for contracting COVID-19, advocating for receipt of recommended COVID-19 vaccinations, and seeking prompt outpatient antiviral treatment after receipt of a positive SARS-CoV-2 test result.

Adverse childhood experiences (ACEs) are preventable, potentially traumatic events occurring before age 18 years. Data on ACEs among adolescents in the United States have primarily been collected through parent report and have not included important violence-related ACEs, including physical, sexual, and emotional abuse. This report presents the first national prevalence of self-reported ACEs among U.S. high school students aged <18 years, estimates associations between ACEs and 16 health conditions and risk behaviors, and calculates population-attributable fractions of ACEs with these conditions and behaviors using cross-sectional, nationally representative 2023 Youth Risk Behavior Survey data. Exposures were lifetime prevalence of individual (emotional, physical, and sexual abuse; physical neglect; witnessed intimate partner violence; household substance use; household poor mental health; and incarcerated or detained parent or guardian) ACEs and cumulative ACEs count (zero, one, two or three, or four or more). Health conditions and risk behaviors included violence risk factors, substance use, sexual behaviors, weight and weight perceptions, mental health, and suicidal thoughts and behaviors. Bivariate analyses assessed associations between individual and cumulative ACEs and demographics. Adjusted prevalence ratios assessed associations between cumulative ACEs and health conditions and risk behaviors, accounting for demographics. Population-attributable fractions were calculated to determine the potential reduction in health conditions and risk behaviors associated with preventing ACEs. ACEs were common, with approximately three in four students (76.1%) experiencing one or more ACEs and approximately one in five students (18.5%) experiencing four or more ACEs. The most common ACEs were emotional abuse (61.5%), physical abuse (31.8%), and household poor mental health (28.4%). Students who identified as female; American Indian or Alaska Native; multiracial; or gay or lesbian, bisexual, questioning, or who describe their sexual identity in some other way experienced the highest number of ACEs. Population-attributable fractions associated with experiencing ACEs were highest for suicide attempts (89.4%), seriously considering attempting suicide (85.4%), and prescription opioid misuse (84.3%). ACEs are prevalent among students and contribute substantially to numerous health conditions and risk behaviors in adolescence. Policymakers and public health professionals can use these findings to understand the potential public health impact of ACEs prevention to reduce adolescent suicidal behaviors, substance use, sexual risk behaviors, and other negative health conditions and risk behaviors and to understand current effects of ACEs among U.S. high school students.

Environmental cleaning is essential to patient and health worker safety, yet it is a substantially neglected area in terms of knowledge, practice, and capacity-building, especially in resource-limited settings. Public health advocacy, research and investment are urgently needed to develop and implement cost-effective interventions to improve environmental cleanliness and, thus, overall healthcare quality and safety. We outline here the CLEAN Group Consensus exercise yielding twelve urgent research questions, grouped into four thematic areas: standards, system strengthening, behaviour change, and innovation.

BACKGROUND: The field of healthcare epidemiology is increasingly focused on identifying, characterizing, and addressing social determinants of health (SDOH) to address inequities in healthcare quality. To identify evidence gaps, we examined recent systematic reviews examining the association of race, ethnicity, and SDOH with inpatient quality measures. METHODS: We searched Medline via OVID for English language systematic reviews from 2010 to 2022 addressing race, ethnicity, or SDOH domains and inpatient quality measures in adults using specific topic questions. We imported all citations to Covidence (www.covidence.org, Veritas Health Innovation) and removed duplicates. Two blinded reviewers assessed all articles for inclusion in 2 phases: title/abstract, then full-text review. Discrepancies were resolved by a third reviewer. RESULTS: Of 472 systematic reviews identified, 39 were included. Of these, 23 examined all-cause mortality; 6 examined 30-day readmission rates; 4 examined length of stay, 4 examined falls, 2 examined surgical site infections (SSIs) and one review examined risk of venous thromboembolism. The most evaluated SDOH measures were sex (n = 9), income and/or employment status (n = 9), age (n = 6), race and ethnicity (n = 6), and education (n = 5). No systematic reviews assessed medication use errors or healthcare-associated infections. We found very limited assessment of other SDOH measures such as economic stability, neighborhood, and health system access. CONCLUSION: A limited number of systematic reviews have examined the association of race, ethnicity and SDOH measures with inpatient quality measures, and existing reviews highlight wide variability in reporting. Future systematic evaluations of SDOH measures are needed to better understand the relationships with inpatient quality measures.

PURPOSE: Adverse childhood experiences (ACEs) increase the risk for poor mental health (MH) and substance use. We describe relationships between adolescents' ACEs, substance use, and poor MH occurring during the COVID-19 pandemic. METHODS: We conducted a secondary analysis of data among U.S. high school students aged <18 years, who participated in the nationally representative Adolescent Behaviors and Experiences Survey. Data were collected from January to June 2021. Bivariate and multivariable analyses assessed associations between individual ACEs (physical, emotional abuse by parent or caregiver, parent or caregiver job loss, food insecurity, sexual violence, physical dating violence, or cyber bullying) and cumulative ACEs (0, 1-2, 3, 4+) experienced during the pandemic and substance use; stratified analyses assessed effects of poor MH on associations between ACEs and substance use. RESULTS: Use of all substances was higher among adolescents with ACEs, particularly those who experienced both ACEs and poor MH during the COVID-19 pandemic. Prevalence of substance use was especially high among adolescents exposed to any sexual violence or physical dating violence. Compared to adolescents without ACEs, a higher percentage of adolescents with 4+ ACEs reported current use of alcohol (adjusted prevalence ratio [aPR], 5.32) or marijuana (aPR, 5.86), misuse of prescription pain medications (aPR, 8.82), binge drinking (aPR, 7.70), and increased alcohol (aPR, 6.54) or drug (aPR, 7.09) use during the pandemic. DISCUSSION: The individual and combined impact of ACEs and MH on adolescent substance use reinforce the need for trauma-informed care and primary prevention of ACEs to prevent and mitigate poor MH and substance use among adolescents.