INTRODUCTION: Previous research suggests that rural-urban disparities in diabetes mortality, hospitalization, and incidence rates may manifest differently across US regions. However, no studies have examined disparities in diabetes prevalence by metropolitan residence and region. METHODS: We used data from the 2019-2022 National Health Interview Survey to compare diabetes status, socioeconomic characteristics, and weight status among adults in each census region (Northeast, Midwest, South, West) according to county metropolitan status of residence (large central metro, large fringe metro, small/medium metro, and nonmetro). We used χ(2) tests and logistic regression models to assess the association of metropolitan residence with diabetes prevalence in each region. RESULTS: Diabetes prevalence ranged from 7.0% in large fringe metro counties in the Northeast to 14.8% in nonmetro counties in the South. Compared with adults from large central metro counties, those from small/medium metro counties had significantly higher odds of diabetes in the Midwest (age-, sex-, and race and ethnicity-adjusted odds ratio [OR] = 1.24; 95% CI, 1.06-1.45) and South (OR = 1.15; 95% CI, 1.02-1.30). Nonmetro residence was also associated with diabetes in the South (OR = 1.62 vs large central metro; 95% CI, 1.43-1.84). After further adjustment for socioeconomic and body weight status, small/medium metro associations with diabetes became nonsignificant, but nonmetro residence in the South remained significantly associated with diabetes (OR = 1.22; 95% CI, 1.07-1.39). CONCLUSION: The association of metropolitan residence with diabetes prevalence differs across US regions. These findings can help to guide efforts in areas where diabetes prevention and care resources may be better directed.

Over-exposure of the hand-arm system to intense vibration and force over time may cause degeneration of the vascular, neurological, and musculoskeletal systems in the fingers. A novel animal model using rat tails has been developed to understand the health effects on human fingers exposed to vibration and force when operating powered hand tools or workpieces. The biodynamic responses, such as vibration stress, strain, and power absorption density, of the rat tails can be used to help evaluate the health effects related to vibration and force and to establish a dose-effect relationship. While the biodynamic responses of cadaver rat tails have been investigated, the objective of the current study was to determine whether the biodynamic responses of living rat tails are different from those of cadaver rat tails, and whether the biodynamic responses of both living and cadaver tails change with exposure duration. To make direct comparisons, the responses of both cadaver and living rat tails were examined on four different testing stations. The transfer function of each tail under a given contact force (2 N) was measured at each frequency in the one-third octave bands from 20 to 1000 Hz, and used to calculate the mechanical system parameters of the tails. The transfer functions were also measured at different exposure durations to determine the time dependency of the response. Differences were observed in the vibration biodynamic responses between living and cadaver tails, but the general trends were similar. The biodynamic responses of both cadaver and living rat tails varied with exposure duration. © 2024 by the authors.

Firefighters face a multitude of hazards in their line of duty, with overexertion being one of the foremost causes of injuries or fatalities. This high risk is often exacerbated by the burden of carrying a heavy self-contained breathing apparatus (SCBA). This study aims to explore the impact of SCBA weight on firefighters' musculoskeletal joint movements. Six firefighters participated in this study, performing four simulated firefighting tasks under three different SCBA weight conditions. A hybrid inverse kinematics approach was employed to analyze the kinematic data from two participants. The results revealed a notable decrease in lumbar range of motion (ROM) as the weight increased, particularly noticeable during hose advancement and stair climbing tasks. Conversely, an increase in hip ROM during stair climbing was observed, suggesting a compensatory response to reduced spinal flexibility. These findings underscore the critical need to understand the implications of turnout gear and SCBA weight to enhance firefighter performance and reduce the risk of injury.

This work aims to investigate and develop a novel phase change material (PCM)-integrated firefighters' turnout gear technology that would significantly enhance the thermal protection of firefighters' bodies from thermal burn injuries under high-heat conditions (such as in fire scenes). This work established a 3D human thermal simulation to explore the thermal protection improvements of firefighters' turnout gear by using PCM segments under flashover and hazardous conditions. This simulation study will guide future experimental design and testing effectively and save time and effort. The study found that the 3.0-mm-thick PCM segments with a melting temperature of 60°C could extend the thermal protection time for skin surface to reach second-degree burn injury (60°C) by one to three times under flashover conditions compared to the turnout gear without PCM. Moreover, thinner PCM segments, i.e., 1.0-3.0 mm thickness, could also significantly mitigate the skin surface temperature increase while avoiding the added weight on the turnout gear. The 3D modelling results can be used to develop a next-generation firefighter turnout gear technology.

Influenza viruses continually evolve new antigenic variants, through mutations in epitopes of their major surface proteins, hemagglutinin (HA) and neuraminidase (NA). Antigenic drift potentiates the reinfection of previously infected individuals, but the contribution of this process to variability in annual epidemics is not well understood. Here, we link influenza A(H3N2) virus evolution to regional epidemic dynamics in the United States during 1997-2019. We integrate phenotypic measures of HA antigenic drift and sequence-based measures of HA and NA fitness to infer antigenic and genetic distances between viruses circulating in successive seasons. We estimate the magnitude, severity, timing, transmission rate, age-specific patterns, and subtype dominance of each regional outbreak and find that genetic distance based on broad sets of epitope sites is the strongest evolutionary predictor of A(H3N2) virus epidemiology. Increased HA and NA epitope distance between seasons correlates with larger, more intense epidemics, higher transmission, greater A(H3N2) subtype dominance, and a greater proportion of cases in adults relative to children, consistent with increased population susceptibility. Based on random forest models, A(H1N1) incidence impacts A(H3N2) epidemics to a greater extent than viral evolution, suggesting that subtype interference is a major driver of influenza A virus infection ynamics, presumably via heterosubtypic cross-immunity. | Seasonal influenza (flu) viruses cause outbreaks every winter. People infected with influenza typically develop mild respiratory symptoms. But flu infections can cause serious illness in young children, older adults and people with chronic medical conditions. Infected or vaccinated individuals develop some immunity, but the viruses evolve quickly to evade these defenses in a process called antigenic drift. As the viruses change, they can re-infect previously immune people. Scientists update the flu vaccine yearly to keep up with this antigenic drift. The immune system fights flu infections by recognizing two proteins, known as antigens, on the virus’s surface, called hemagglutinin (HA) and neuraminidase (NA). However, mutations in the genes encoding these proteins can make them unrecognizable, letting the virus slip past the immune system. Scientists would like to know how these changes affect the size, severity and timing of annual influenza outbreaks. Perofsky et al. show that tracking genetic changes in HA and NA may help improve flu season predictions. The experiments compared the severity of 22 flu seasons caused by the A(H3N2) subtype in the United States with how much HA and NA had evolved since the previous year. The A(H3N2) subtype experiences the fastest rates of antigenic drift and causes more cases and deaths than other seasonal flu viruses. Genetic changes in HA and NA were a better predictor of A(H3N2) outbreak severity than the blood tests for protective antibodies that epidemiologists traditionally use to track flu evolution. However, the prevalence of another subtype of influenza A circulating in the population, called A(H1N1), was an even better predictor of how severe A(H3N2) outbreaks would be. Perofsky et al. are the first to show that genetic changes in NA contribute to the severity of flu seasons. Previous studies suggested a link between genetic changes in HA and flu season severity, and flu vaccines include the HA protein to help the body recognize new influenza strains. The results suggest that adding the NA protein to flu vaccines may improve their effectiveness. In the future, flu forecasters may want to analyze genetic changes in both NA and HA to make their outbreak predictions. Tracking how much of the A(H1N1) subtype is circulating may also be useful for predicting the severity of A(H3N2) outbreaks. | eng

BACKGROUND: The optimal antiviral drug for treatment of severe influenza remains unclear. To support updated WHO influenza clinical guidelines, this systematic review and network meta-analysis evaluated antivirals for treatment of patients with severe influenza. METHODS: We systematically searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Global Health, Epistemonikos, and ClinicalTrials.gov for randomised controlled trials published up to Sept 20, 2023, that enrolled hospitalised patients with suspected or laboratory-confirmed influenza and compared direct-acting influenza antivirals against placebo, standard care, or another antiviral. Pairs of coauthors independently extracted data on study characteristics, patient characteristics, antiviral characteristics, and outcomes, with discrepancies resolved by discussion or by a third coauthor. Key outcomes of interest were time to alleviation of symptoms, duration of hospitalisation, admission to intensive care unit, progression to invasive mechanical ventilation, duration of mechanical ventilation, mortality, hospital discharge destination, emergence of antiviral resistance, adverse events, adverse events related to treatments, and serious adverse events. We conducted frequentist network meta-analyses to summarise the evidence and evaluated the certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. This study is registered with PROSPERO, CRD42023456650. FINDINGS: Of 11 878 records identified by our search, eight trials with 1424 participants (mean age 36-60 years for trials that reported mean or median age; 43-78% male patients) were included in this systematic review, of which six were included in the network meta-analysis. The effects of oseltamivir, peramivir, or zanamivir on mortality compared with placebo or standard care without placebo for seasonal and zoonotic influenza were of very low certainty. Compared with placebo or standard care, we found low certainty evidence that duration of hospitalisation for seasonal influenza was reduced with oseltamivir (mean difference -1·63 days, 95% CI -2·81 to -0·45) and peramivir (-1·73 days, -3·33 to -0·13). Compared with standard care, there was little or no difference in time to alleviation of symptoms with oseltamivir (0·34 days, -0·86 to 1·54; low certainty evidence) or peramivir (-0·05 days, -0·69 to 0·59; low certainty evidence). There were no differences in adverse events or serious adverse events with oseltamivir, peramivir, and zanamivir (very low certainty evidence). Uncertainty remains about the effects of antivirals on other outcomes for patients with severe influenza. Due to the small number of eligible trials, we could not test for publication bias. INTERPRETATION: In hospitalised patients with severe influenza, oseltamivir and peramivir might reduce duration of hospitalisation compared with standard care or placebo, although the certainty of evidence is low. The effects of all antivirals on mortality and other important patient outcomes are very uncertain due to scarce data from randomised controlled trials. FUNDING: World Health Organization.

INTRODUCTION: Acute kidney injury (AKI) is associated with increased mortality. AKI-related mortality trends by US urban and rural counties were assessed. METHODS: In the cross-sectional study, based on the Centers for Disease Control and Prevention WONDER (Wide-ranging ONline Data for Epidemiologic Research) Multiple Cause of Death data, age-standardized mortality with AKI as the multiple cause was obtained among adults aged ≥25 years from 2001-2020, by age, sex, race and ethnicity, stratified by urban-rural counties. Joinpoint regressions were used to assess trends from 2001-2019 in AKI-related mortality rate. Pairwise comparison was used to compare mean differences in mortality between urban and rural counties from 2001-2019. RESULTS: From 2001-2020, age-standardized AKI-related mortality was consistently higher in rural than urban counties. AKI-related mortality (per 100,000 population) increased from 18.95 in 2001 to 29.46 in 2020 in urban counties and from 20.10 in 2001 to 38.24 in 2020 in rural counties. In urban counties, AKI-related mortality increased annually by 4.6% during 2001-2009 and decreased annually by 1.8% until 2019 (p<0.001). In rural counties, AKI-related mortality increased annually by 5.0% during 2001-2011 and decreased by 1.2% until 2019 (p<0.01). The overall urban-rural difference in AKI-related mortality was greater after 2009-2011. AKI-related mortality was significantly higher among older adults, men, and non-Hispanic Black adults than their counterparts in both urban and rural counties. Higher mortality was concentrated in rural counties in the Southern United States. CONCLUSIONS: Multidisciplinary efforts are needed to increase AKI awareness and implement strategies to reduce AKI-related mortality in rural and high-risk populations.

PURPOSE: To assess the occurrence of tinnitus following COVID-19 vaccination using data mining and descriptive analyses in two U.S. vaccine safety surveillance systems. METHODS: Reports of tinnitus after COVID-19 vaccination to the Vaccine Adverse Event Reporting System (VAERS) from 2020 through 2024 were examined using empirical Bayesian data mining and by calculating reporting rates. In the Vaccine Safety Datalink (VSD) population, ICD-10 coded post-vaccination medical visits were examined using tree-based data mining, and tinnitus visit incidence rates during post-vaccination days 1-140 were calculated by age group for COVID-19 vaccines and for comparison, influenza vaccine. RESULTS: VAERS data mining did not find disproportionate reporting of tinnitus for any COVID-19 vaccine. VAERS received up to 84.82 tinnitus reports per million COVID-19 vaccine doses administered. VSD tree-based data mining found no signals for tinnitus. VSD tinnitus visit incidence rates after COVID-19 vaccines were similar to those after influenza vaccine except for the group aged ≥65 years (Moderna COVID-19 vaccine, 165 per 10,000 person-years; Pfizer-BioNTech COVID-19 vaccine, 154; influenza vaccine, 135). CONCLUSIONS: Overall, these findings do not support an increased risk of tinnitus following COVID-19 vaccination but cannot definitively exclude the possibility. Descriptive comparisons between COVID-19 and influenza vaccines were limited by lack of adjustment for potential confounding factors.

OBJECTIVE: Injuries and poisoning are leading causes of US morbidity and mortality. This study aimed to update medical and work loss cost estimates per injured person. METHODS: Injuries treated in emergency departments (ED) during 2019-2020 were analysed in terms of mechanism (eg, fall) and intent (eg, unintentional), as well as traumatic brain injury (TBI) (multiple mechanisms and intents). Fatal injury medical spending was based on the Nationwide Emergency Department Sample and National Inpatient Sample. Non-fatal injury medical spending and workplace absences (general, short-term disability and workers' compensation) were analysed among injury patients with commercial insurance or Medicaid and matched controls during the year following an injury ED visit using MarketScan databases. RESULTS: Medical spending for injury deaths in hospital EDs and inpatient settings averaged US$4777 (n=57 296) and US$45 678 per fatality (n=89 175) (2020 USD). Estimates for fatal TBI were US$5052 (n=5363) and US$47 952 (n=37 184). People with ED treat and release visits for non-fatal injuries had on average US$5798 (n=895 918) in attributable medical spending and US$1686 (11 missed days) (n=116 836) in work loss costs during the following year, while people with non-fatal injuries who required hospitalisation after an ED injury visit had US$52 246 (n=32 976) in medical spending and US$7815 (51 days) (n=4473) in work loss costs. Estimates for non-fatal TBI were US$4529 (n=25 792), US$1503 (10 days) (n=1631), US$51 241 (n=3030) and US$6110 (40 days) (n=246). CONCLUSIONS AND RELEVANCE: Per person costs of injuries and violence are important to monitor the economic burden of injuries and assess the value of prevention strategies.

RATIONALE: Optimizing pyrazinamide dosing is critical to improve treatment efficacy while minimizing toxicity during tuberculosis treatment. Study 31/ACTG A5349 represents the largest Phase 3 randomized controlled therapeutic trial to date for such investigation. OBJECTIVES: We sought to report pyrazinamide pharmacokinetic parameters, risk factors for lower pyrazinamide exposure, and relationships between pyrazinamide exposure with efficacy and safety outcomes. We aimed to determine pyrazinamide dosing strategies that optimize risks and benefits. METHODS: We analyzed pyrazinamide steady-state pharmacokinetic data using population nonlinear mixed-effects models. We evaluated the contribution of pyrazinamide exposure to long-term efficacy using parametric time-to-event models and safety outcomes using logistic regression. We evaluated optimal dosing with therapeutic windows targeting ≥95% durable cure and safety within the observed proportion of the primary safety outcome. MEASUREMENTS AND MAIN RESULTS: Among 2255 participants with 6978 plasma samples, pyrazinamide displayed 7-fold exposure variability (151-1053 mg·h/L). Body weight was not a clinically relevant predictor of drug clearance and thus did not justify the need for weight-banded dosing. Both clinical and safety outcomes were associated with pyrazinamide exposure, resulting in a therapeutic window of 231-355 mg·h/L for the control and 226-349 mg·h/L for the rifapentine-moxifloxacin regimen. Flat dosing of pyrazinamide at 1000 mg would have permitted an additional 13.1% (n=96) participants allocated to the control and 9.2% (n=70) to the rifapentine-moxifloxacin regimen dosed within the therapeutic window, compared to the current weight-banded dosing. CONCLUSIONS: Flat dosing of pyrazinamide at 1000 mg daily would be readily implementable and could optimize treatment outcomes in drug-susceptible tuberculosis. Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT02410772.

Firefighters wear personal protective equipment to protect them from the thermal and chemical environment in which they operate. The self-contained breathing apparatus (SCBA) provides isolation of the airway from the hazardous fireground. National standards limit SCBA weight, however, integration of additional features could result in an SCBA exceeding the current limit. The purpose of this study was to examine the effects of increased SCBA weight on firefighters' physiological responses, work output, dynamic stability, and comfort. Completion of simulated firefighting activities induced a strong physiological response. Peak oxygen consumption was higher with the lightest SCBA than the heaviest SCBA. Few other physiological differences were noted as SCBA weight increased. Importantly, increased SCBA weight resulted in significantly more negative perceptions by the firefighters and a trend towards significance for the duration of work time prior to reaching volitional fatigue. These results should be considered when assessing changes to existing SCBA weight limits. | Increased SCBA weight above existing national standards resulted in negative perceptions by the firefighters, but not significant physiological changes after two simulated bouts of firefighting activity. SCBA weight had a nearly significant impact on the time firefighters worked before reaching volitional fatigue, with heavier SCBA trending towards decreased working time. | eng

IMPORTANCE: People with HIV (PWH) may be at increased risk for severe outcomes with COVID-19 illness compared with people without HIV. Little is known about COVID-19 vaccination coverage and factors associated with primary series completion among PWH. OBJECTIVES: To evaluate COVID-19 vaccination coverage among PWH and examine sociodemographic, clinical, and community-level factors associated with completion of the primary series and an additional primary dose. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used electronic health record data to assess COVID-19 vaccination information from December 14, 2020, through April 30, 2022, from 8 health care organizations of the Vaccine Safety Datalink project in the US. Participants were adults diagnosed with HIV on or before December 14, 2020, enrolled in a participating site. MAIN OUTCOMES AND MEASURES: The percentage of PWH with at least 1 dose of COVID-19 vaccine and PWH who completed the COVID-19 vaccine primary series by December 31, 2021, and an additional primary dose by April 30, 2022. Rate ratios (RR) and 95% CIs were estimated using Poisson regression models for factors associated with completing the COVID-19 vaccine primary series and receiving an additional primary dose. RESULTS: Among 22 058 adult PWH (mean [SD] age, 52.1 [13.3] years; 88.8% male), 90.5% completed the primary series by December 31, 2021. Among 18 374 eligible PWH who completed the primary series by August 12, 2021, 15 982 (87.0%) received an additional primary dose, and 4318 (23.5%) received a booster dose by April 30, 2022. Receipt of influenza vaccines in the last 2 years was associated with completion of the primary series (RR, 1.17; 95% CI, 1.15-1.20) and an additional primary dose (RR, 1.61; 95% CI, 1.54-1.69). PWH with uncontrolled viremia (HIV viral load ≥200 copies/mL) (eg, RR, 0.90 [95% CI, 0.85-0.95] for viral load 200-10 000 copies/mL vs undetected or <200 copies/mL for completing the primary series) and Medicaid insurance (eg, RR, 0.89 [95% CI, 0.87-0.90] for completing the primary series) were less likely to be fully vaccinated. By contrast, greater outpatient utilization (eg, RR, 1.07 [95% CI, 1.05-1.09] for ≥7 vs 0 visits for primary series completion) and residence in counties with higher COVID-19 vaccine coverage (eg, RR, 1.06 [95% CI, 1.03-1.08] for fourth vs first quartiles for primary series completion) were associated with primary series and additional dose completion (RRs ranging from 1.01 to 1.21). CONCLUSIONS AND RELEVANCE: Findings from this cohort study suggest that, while COVID-19 vaccination coverage was high among PWH, outreach efforts should focus on those who did not complete vaccine series and those who have uncontrolled viremia.

OBJECTIVE: Linkage to HIV medical care is important in the continuum of HIV care and health outcomes for people with HIV. The objective of this analysis was to identify how the community-based organization (CBO) program contributes to linkage to HIV medical care among people with newly diagnosed HIV in the Centers for Disease Control and Prevention's (CDC's) HIV testing program. METHODS: We analyzed HIV linkage-to-care data submitted to CDC from 2019 through 2021. Linkage was defined as confirmation that an individual attended their first HIV medical care appointment within 30 days of their HIV test date. We included in the analysis data submitted from the health department (HD) program that included 61 state and local HDs in the United States, Puerto Rico, and the US Virgin Islands and the CBO program that included 150 CBOs. RESULTS: The CBO program linked a higher proportion of people to HIV medical care within 30 days of diagnosis (86.7%) than the HD program (73.7%). By population group, the proportion linked in the CBO program was higher than the proportion linked in the HD program among men who have sex with men (prevalence ratio [PR] = 1.13; P < .001), men who have sex with men/people who inject drugs (PR = 1.29; P < .001), transgender people (PR = 1.28; P < .001), and those reporting no sexual contact or injection drug use (PR = 1.34; P < .001). In the Cox proportional hazards model, time to linkage in the CBO program was significantly shorter than in the HD program (hazard ratio = 0.63; P < .001). CONCLUSION: This analysis shows that the CBO program fills a vital need in linking newly diagnosed HIV-positive people to HIV medical care, which is important in the HIV care continuum and for viral suppression.

Understanding the factors influencing mosquitoes' fecundity and longevity is important for designing better and more sustainable vector control strategies, as these parameters can impact their vectorial capacity. Here, we address how mating affects midgut growth in Aedes aegypti, what role Juvenile Hormone (JH) plays in this process, and how it impacts the mosquito's immune response and microbiota. Our findings reveal that mating and JH induce midgut growth. Additionally, the establishment of a native bacterial population in the midgut due to JH-dependent suppression of the immune response has important reproductive outcomes. Specific downregulation of AMPs with an increase in bacteria abundance in the gut results in increased egg counts and longer lifespans. Overall, these findings provide evidence of a cross-talk between JH response, gut epithelial tissue, cell cycle regulation, and the mechanisms governing the trade-offs between nutrition, immunity, and reproduction at the cellular level in the mosquito gut.

BACKGROUND: Empirical studies have demonstrated associations between ten original adverse childhood experiences (ACEs) and multiple health outcomes. Identifying expanded ACEs can capture the burden of other childhood adversities that may have important health implications. OBJECTIVE: We sought to identify childhood adversities that warrant consideration as expanded ACEs. We hypothesized that experiencing expanded and original ACEs would be associated with poorer adult health outcomes compared to experiencing original ACEs alone. PARTICIPANTS: The 11,545 respondents of the National Longitudinal Surveys (NLS) and Child and Young Adult Survey were 48.9 % female, 22.7 % Black, 15.8 % Hispanic, 36.1 % White, 1.7 % Asian/Native Hawaiian/Pacific Islander/Native American/Native Alaskan, and 7.5 % Other. METHODS: This study used regression trees and generalized linear models to identify if/which expanded ACEs interacted with original ACEs in association with six health outcomes. RESULTS: Four expanded ACEs-basic needs instability, lack of parental love and affection, community stressors, and mother's experience with physical abuse during childhood -significantly interacted with general health, depressive symptom severity, anxiety symptom severity, and violent crime victimization in adulthood (all p-values <0.005). Basic needs instability and/or lack of parental love and affection emerged as correlates across multiple outcomes. Experiencing lack of parental love and affection and original ACEs was associated with greater anxiety symptoms (p = 0.022). CONCLUSIONS: This is the first study to use supervised machine learning to investigate interaction effects among original ACEs and expanded ACEs. Two expanded ACEs emerged as predictors for three adult health outcomes and warrant further consideration in ACEs assessments.

During the COVID-19 pandemic, forecasting COVID-19 trends to support planning and response was a priority for scientists and decision makers alike. In the United States, COVID-19 forecasting was coordinated by a large group of universities, companies, and government entities led by the Centers for Disease Control and Prevention and the US COVID-19 Forecast Hub (https://covid19forecasthub.org). We evaluated approximately 9.7 million forecasts of weekly state-level COVID-19 cases for predictions 1-4 weeks into the future submitted by 24 teams from August 2020 to December 2021. We assessed coverage of central prediction intervals and weighted interval scores (WIS), adjusting for missing forecasts relative to a baseline forecast, and used a Gaussian generalized estimating equation (GEE) model to evaluate differences in skill across epidemic phases that were defined by the effective reproduction number. Overall, we found high variation in skill across individual models, with ensemble-based forecasts outperforming other approaches. Forecast skill relative to the baseline was generally higher for larger jurisdictions (e.g., states compared to counties). Over time, forecasts generally performed worst in periods of rapid changes in reported cases (either in increasing or decreasing epidemic phases) with 95% prediction interval coverage dropping below 50% during the growth phases of the winter 2020, Delta, and Omicron waves. Ideally, case forecasts could serve as a leading indicator of changes in transmission dynamics. However, while most COVID-19 case forecasts outperformed a naïve baseline model, even the most accurate case forecasts were unreliable in key phases. Further research could improve forecasts of leading indicators, like COVID-19 cases, by leveraging additional real-time data, addressing performance across phases, improving the characterization of forecast confidence, and ensuring that forecasts were coherent across spatial scales. In the meantime, it is critical for forecast users to appreciate current limitations and use a broad set of indicators to inform pandemic-related decision making.

BACKGROUND: Preventive care is important for managing inflammatory bowel disease (IBD), yet primary care providers (PCPs) often face challenges in delivering such care due to discomfort and unfamiliarity with IBD-specific guidelines. This study aims to assess PCPs' attitudes towards, and practices in, providing preventive screenings for IBD patients, highlighting areas for improvement in guideline dissemination and education. METHODS: Using a web-based opt-in panel of PCPs (DocStyles survey, spring 2022), we assessed PCPs' comfort level with providing/recommending screenings and the reasons PCPs felt uncomfortable (n = 1,503). Being likely to provide/recommend screenings for depression/anxiety, skin cancer, osteoporosis, and cervical cancer were compared by PCPs' comfort level and frequency of seeing patients with IBD. We estimated adjusted odd ratios (AORs) of being likely to recommend screenings and selecting responses aligned with IBD-specific guidelines by use of clinical practice methods. RESULTS: About 72% of PCPs reported being comfortable recommending screenings to patients with IBD. The top reason identified for not feeling comfortable was unfamiliarity with IBD-specific screening guidelines (55%). Being comfortable was significantly associated with being likely to provide/recommend depression/anxiety (AOR = 3.99) and skin cancer screenings (AOR = 3.19) compared to being uncomfortable or unsure. Percentages of responses aligned with IBD-specific guidelines were lower than those aligned with general population guidelines for osteoporosis (21.7% vs. 27.8%) and cervical cancer screenings (34.9% vs. 43.9%), and responses aligned with IBD-specific guidelines did not differ by comfort level for both screenings. Timely review of guidelines specific to immunosuppressed patients was associated with being likely to provide/recommend screenings and selecting responses aligned with IBD-specific guidelines. CONCLUSIONS: Despite a general comfort among PCPs in recommending preventive screenings for IBD patients, gaps in knowledge regarding IBD-specific screening guidelines persist. Enhancing awareness and understanding of these guidelines through targeted education and resource provision may bridge this gap.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are ubiquitous environmental chemicals used as flame retardants in commercial and consumer products. Gestational PBDE concentrations are associated with adverse behaviors in children; however, the persistence of these associations into adolescence remains understudied. OBJECTIVE: We estimated the association of gestational PBDE serum concentrations with early adolescent self- and caregiver-reported behaviors at age 12 years and determined the consistency with previously observed associations in childhood with caregiver-reported behaviors in a prospective pregnancy and birth cohort. METHODS: We measured maternal serum concentrations of five individual PBDE congeners and created a summary exposure variable (∑(5)BDE: 28, -47, -99, -100 and -153) during pregnancy. At age 12 years, we assessed behaviors for 237 adolescents using self- and caregiver-reports with the Behavioral Assessment System for Children-3 (BASC3). We used multivariable linear regression models to estimate covariate-adjusted associations of lipid standardized, log(10)-transformed gestational PBDE concentrations with BASC3 scores. We obtained estimates and 95% confidence intervals through a bootstrapping approach. We evaluated potential effect measure modification (EMM) of adolescent sex by examining sex-stratified regression models and estimating the EMM p-values. RESULTS: Gestational PBDE concentrations were positively associated with adolescent-reported BASC3 composite indices for inattention & hyperactivity (BDE-28, -47, -99, -100, ∑(5)BDE), internalizing problems (BDE-28, -47, -99), functional impairment (BDE-28, ∑(5)BDE), and emotional symptoms (BDE-28). Gestational PBDE concentrations were positively associated with caregiver-reported BASC3 composite indices for externalizing problems (BDE-28, -47, -99, -100, -153, ∑(5)BDE) and behavioral symptoms (BDE-99). For caregiver reported behaviors, we observed stronger associations with gestational BDE concentrations among males, especially for executive functioning (BDE-28, -47, -99, -100, ∑(5)BDE). DISCUSSION: Gestational PBDE serum concentrations were associated with self-reported internalizing and externalizing behavior problems in early adolescence. Caregiver-reported externalizing behaviors recognized during childhood remain associated with gestational PBDE concentrations and persist into early adolescence. Internalizing behaviors were less recognized by caregivers.

The purpose of this analysis is to describe HIV tests and associated outcomes for Asian people reached by the Centers for Disease Control and Prevention (CDC) HIV testing program. We analyzed CDC-funded HIV tests among Asian individuals in the United States, Puerto Rico, and the U.S. Virgin Islands (2014-2020). Of the 415,560 tests, the positivity of new diagnoses was higher among males (0.49%, aPR = 7.64) than females (0.06%), and in the West (0.42%, aPR = 1.15) than in the South (0.25%). In non-health care settings, positivity was highest among men who have sex with men (MSM; 0.87%) and transgender people (0.46%). Linkage to HIV medical care among Asian people was 87.5%, and 70.7% were interviewed for partner services. Our findings suggest that improvements are crucial, particularly for Asian MSM, in linkage to care and interview for partner services.

BACKGROUND: Triclosan is an endocrine-disrupting chemical, but associations with pubertal outcomes remain unclear. We examined associations of gestational and childhood triclosan with adolescent hormone concentrations and pubertal stage. METHODS: We quantified urinary triclosan concentrations twice during pregnancy and seven times between birth and 12 years in participants recruited from Cincinnati, OH (2003-2006). We averaged concentrations across pregnancy and childhood and separately considered individual exposure periods in multiple informant models. At 12 years, we measured serum hormone concentrations (males [n = 72] and females [n = 84]-dehydroepiandrosterone-sulfate, luteinizing hormone, follicle-stimulating hormone; males-testosterone; females-estradiol). Also at age 12 years, participants self-reported physical development and menarchal timing. We estimated associations (95% confidence interval) of triclosan with hormone concentrations, more advanced physical development, and age at menarche. RESULTS: For females, each doubling of childhood triclosan was associated with 16% lower estradiol concentrations (-29%, 0%), with stronger associations for measures closer to adolescence. We found suggestive evidence that higher triclosan at any age was associated with ~10% (for gestational triclosan: -18%, -2%) lower follicle-stimulating hormone concentrations among males and early postnatal (1-3 years) triclosan was associated with 63% (5%, 96%) lower odds of advanced pubic hair development in females. In multiple informant models, each doubling of gestational triclosan concentrations was associated with 5% (0%, 9%) earlier age at menarche, equivalent to 5.5 months. CONCLUSION: Gestational and childhood triclosan concentrations were related to some pubertal outcomes including hormone concentrations and age at menarche. Our findings highlight the relevance of elucidating potential sex-specific and time-dependent actions of triclosan.

Phase change material (PCM) has been widely studied for efficient thermal management. This work is the first holistic experimental research on the temperature control performance of PCM-integrated firefighters' gloves. The results showed that the thermal protection time could be extended by 2-5 times in the direct contact to hot object tests and around 1.5 times under the radiant/convective heat source tests when embedding a 1-mm-thick PCM layer in gloves. The PCM of melting point 68 °C showed the best thermal protection performance in all test conditions since it had the most efficient phase change function during the heating process. Considering the PCM location effect, the PCM with lower melting point (68 °C) showed better performance when located close to external environment (heat source) and the PCM with higher melting point (108 °C and 151 °C) showed better performance when located close to hand. The optimum PCM thickness would be in the range of 0.5-1.0 mm for both thermal protection improvement and hand dexterity purposes. In addition, the time for continuous temperature rises on the hand surface at post-heat exposure was longer when embedding PCM in firefighters’ gloves due to the stored latent heat in PCM. © 2024 The Authors

Amoxicillin, doxycycline, and clindamycin are among the commonly used antibiotics to treat bacterial infections. However, dosage forms of antibiotics for pediatric patients may not be as readily available as the formulations for adult patients. As such, it is anticipated that during a public health emergency, special instruction may need to be provided on home preparation and administration procedures to dose pediatric patients using available stockpiles of oral tablet and capsule dosage forms. Mixing crushed tablets or capsule contents with soft- or liquid- foods is one of the most common home preparation procedures. To gain knowledge for safe and effective use of prepared drug product instead of the intended intact dosage form, the impact of manipulation of the dosage form was studied. Capsule opening, capsule content assay and uniformity, dissolution, homogeneity, and stability studies of drug mixed with various liquid and soft foods were carried out using intact capsules of amoxicillin, doxycycline, and clindamycin. Higher recovery of capsule contents was achieved when using hands or knives to open capsules compared to using scissors. The capsules of all three antibiotic products contained the labeled amount of active pharmaceutical ingredients (API). The peanut butter-drug mixtures failed both United States Pharmacopeia (USP) assay and dissolution criteria because the peanut butter significantly affected the solubility of the drugs, and hence it was omitted from further study. All drug-food mixtures of the three antibiotic products and 15 selected foods exhibited fast dissolution (e.g., >80 % in 60 min) in the tested medium, except for the amoxicillin-chocolate pudding mixture. Three household containers (cups, plates, and bowls) and four mixing times (0.5 min, 1 min, 2 min, and 5 min) were found to be suitable for preparation of homogeneous mixtures of the antibiotics and foods. For practical purposes, 1 to 2 min mixing time is sufficient to produce homogeneous mixtures. The results of this study provided product quality data on the interactions between the antibiotics and the foods and can potentially support future development of home preparation instructions of antibiotics for pediatric patients or patients with swallowing difficulties.

BACKGROUND: The optimal dosing strategy for rifampicin in treating drug-susceptible tuberculosis (TB) is still highly debated. In the Phase 3 clinical trial Study 31/ACTG 5349 (NCT02410772), all participants in the control regimen arm received 600 mg rifampicin daily as a flat dose. Here, we evaluated relationships between rifampicin exposure and efficacy and safety outcomes. METHODS: We analyzed rifampicin concentration time profiles using population nonlinear mixed-effects models. We compared simulated rifampicin exposure from flat- and weight-banded dosing. We evaluated the effect of rifampicin exposure on stable culture conversion at 6 months, TB-related unfavorable outcomes at 9, 12, and 18 months using Cox proportional hazard models, and all trial-defined safety outcomes using logistic regression. RESULTS: Our model derived rifampicin exposure ranged from 4.57 mg·h/L to 140.0 mg·h/L with a median of 41.8 mg·h/L. Pharmacokinetic simulations demonstrated that flat-dosed rifampicin provided exposure coverage similar to weight-banded dose. Exposure-efficacy analysis (N=680) showed that participants with rifampicin exposure below the median experienced similar hazards of stable culture conversion and TB-related unfavorable outcomes compared to those with exposure above the median. Exposure-safety analysis (N=722) showed that increased rifampicin exposure was not associated with increased grade 3 or higher adverse events, or serious adverse events. CONCLUSIONS: Flat-dosing of rifampicin at 600 mg daily may be a reasonable alternative to the incumbent weight-banded dosing strategy for the standard of care 6-month regimen. Future research should assess the optimal dosing strategy for rifampicin, at doses higher than the current recommendation.

BACKGROUND: Although previous studies found no-increased mortality risk after COVID-19 vaccination, residual confounding bias might have impacted the findings. Using a modified self-controlled case series (SCCS) design, we assessed the risk of non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes after primary series COVID-19 vaccination. METHODS: We analyzed all deaths between December 14, 2020, and August 11, 2021, among individuals from eight Vaccine Safety Datalink sites. Demographic characteristics of deaths in recipients of COVID-19 vaccines and unvaccinated individuals were reported. We conducted SCCS analyses by vaccine type and death outcomes and reported relative incidences (RI). The observation period for death spanned from the dates of emergency use authorization to the end of the study period (August 11, 2021) without censoring the observation period upon death. We pre-specified a primary risk interval of 28-day and a secondary risk interval of 14-day after each vaccination dose. Adjusting for seasonality in mortality analyses is crucial because death rates vary over time. Deaths among unvaccinated individuals were included in SCCS analyses to account for seasonality by incorporating calendar month in the models. RESULTS: For Pfizer-BioNTech (BNT162b2), RIs of non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes were below 1 and 95 % confidence intervals (CIs) excluded 1 across both doses and both risk intervals. For Moderna (mRNA-1273), RI point estimates of all outcomes were below 1, although the 95 % CIs of two RI estimates included 1: cardiac-related (RI = 0.78, 95 % CI, 0.58-1.04) and non-COVID-19 cardiac-related mortality (RI = 0.80, 95 % CI, 0.60-1.08) 14 days after the second dose in individuals without pre-existing cancer and heart disease. For Janssen (Ad26.COV2.S), RIs of four cardiac-related death outcomes ranged from 0.94 to 0.98 for the 14-day risk interval, and 0.68 to 0.72 for the 28-day risk interval and 95 % CIs included 1. CONCLUSION: Using a modified SCCS design and adjusting for temporal trends, no-increased risk was found for non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes among recipients of the three COVID-19 vaccines used in the US.

INTRODUCTION: Physical activity (PA) can reduce morbidity and mortality among adults with diabetes. While rural disparities in PA exist among the general population, it is not known how these disparities manifest among adults with diabetes. METHODS: Data from the 2020 and 2022 National Health Interview Survey were analyzed in 2023 to assess prevalence of meeting aerobic and muscle-strengthening recommendations according to the 2018 Physical Activity Guidelines for Americans during leisure time. PA prevalence was computed by diabetes status, type of PA, and urban/rural residence (large central metro, large fringe metro, medium/small metro, and non-metro). Logistic regression models were used to estimate prevalence and prevalence ratios of meeting PA recommendations by urban/rural residence across diabetes status. RESULTS: Among adults with diabetes in non-metro counties, only 23.8% met aerobic, 10.9% met muscle-strengthening, and 6.2% met both PA recommendations. By contrast, among adults with diabetes in large fringe metro counties, 32.1% met aerobic, 19.7% met strengthening, and 12.0% met both guidelines. Multivariable adjusted prevalence of meeting muscle-strengthening recommendations was higher among participants with diabetes in large fringe metro compared to large central metro counties (PR=1.27; 95% CI 1.03-1.56). Among those without diabetes, adjusted prevalence of meeting each recommendation or both was lower in non-metro and small/medium metro compared to large central metro counties. CONCLUSIONS: Adults with diabetes are less likely to meet the PA recommendations than those without, and differences exist according to urban/rural status. Improving PA among rural residents with diabetes may mitigate disparities in diabetes-related mortality.

BACKGROUND: Opioid agonist therapies (OAT) for people with opioid use disorders (OUD) have been available in Ukraine since 2004. This study assessed the effect of 2014 Russian invasion of Ukraine on OAT re-enrollment and retention in conflict areas. METHODS: We analyzed the Ukraine national registry of OAT patients containing 1868 people with OUD receiving OAT as of January 2014 in conflict areas (Donetsk, Luhansk, and the Autonomous Republic [AR] of the Crimea). We developed logistic regression models to assess the correlates of re-enrollment of OAT patients in government-controlled areas (GCA) from conflict areas and retention on OAT at 12 months after re-enrollment. RESULTS: Overall, 377 (20.2 %) patients were re-enrolled at an OAT site in a GCA from confict areas, of whom 182 (48.3 %) were retained on OAT through 2021. Correlates of re-enrollment were residing in Donetsk (adjusted odds ratios (aOR) = 7.06; 95 % CI: 4.97-10.20) or Luhansk (aOR = 6.20; 95 % CI: 4.38-8.93) vs. AR Crimea; age 18-34 (aOR = 2.03; 95 % CI: 1.07-3.96) or 35-44 (aOR = 2.09; 95 % CI: 1.24-3.71) vs. ≥55 years, and being on optimal (aOR = 1.78; 95 % CI: 1.33-2.39) or high OAT dosing (aOR = 2.76; 95 % CI: 1.93-3.96) vs. low dosing. Correlates of retention were drug use experience 15-19 years (aOR = 3.69; 95 % CI: 1.47-9.49) vs. <14 years of drug use; take-home (aOR = 3.42; 95 % CI: 1.99-5.96) vs. daily on-site dosing, and optimal (aOR = 2.19; 95 % CI:1.05-4.72) vs. low OAT dosing. CONCLUSION: Our study showed that one-fifth of patients were re-enrolled at sites in GCA areas, less than half of re-enrolled patients were retained. Disruption of OAT has implications for drug-, HIV-, and HCV-related morbidity and mortality. FUNDING: AM was funded by NIH-funded grant D43TW010562; DCO was funded by the NIDA-funded Center for Drug Use and HIV|HCV Research (P30DA011041).

BACKGROUND: Tuberculosis (TB) infection prevention and control (IPC) in healthcare facilities is key to reducing transmission risk. A framework for systematically improving TB IPC through training and mentorship was implemented in 9 healthcare facilities in China from 2017 to 2019. METHODS: Facilities conducted standardized TB IPC assessments at baseline and quarterly thereafter for 18 months. Facility-based performance was assessed using quantifiable indicators for IPC core components and administrative, environmental, and respiratory protection controls, and as a composite of all control types We calculated the percentage changes in scores over time and differences by IPC control type and facility characteristics. RESULTS: Scores for IPC core components increased by 72% during follow-up when averaged across facilities. The percentage changes for administrative, environmental, and respiratory protection controls were 39%, 46%, and 30%, respectively. Composite scores were 45% higher after the intervention. Overall, scores increased most during the first 6 months. There was no association between IPC implementation and provincial economic development or volume of TB services. CONCLUSIONS: TB IPC policies and practices showed most improvement early during implementation and did not differ consistently by facility characteristics. The training component of the project helped increase the capacity of healthcare professionals to manage TB transmission risks. Lessons learned here will inform national TB IPC guidance.