OBJECTIVE: To develop a U.S.-based microsimulation model for assessing the cost-effectiveness of interventions to manage type 1 diabetes. RESEARCH DESIGN AND METHODS: We developed risk equations for 14 diabetes-related complications and mortality, 12 risk factor progression equations, and one equation for utilities associated with 14 complications using data from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) studies and the Epidemiology of Diabetes Complications (EDC) study. We integrated all equations into a simulation model. We conducted internal and external validation and demonstrated the utility of the model using a real-world example. Main model-generated outcomes included cumulative incidence of diabetes-related complications, life years, quality-adjusted life years, medical costs, and incremental cost-effectiveness ratios. RESULTS: The model generates long-term clinical and economic outcomes from changes in risk factors of type 1 diabetes complications. Internal validation comparing modeled outcomes to observed data used to develop the model yielded good prediction accuracy, with mean absolute percentage error across all complications of 9% and correlation of cumulative failure rates above 0.9. External validation results were mixed, with occurrence of slight under- or overprediction across complications and studies. We illustrated the model with a case study estimating the effects of expanding the use of an insulin pump with continuous glucose monitoring to all people with type 1 diabetes. CONCLUSIONS: Our new comprehensive type 1 diabetes simulation model can generate valid and accurate results for assessing the long-term cost-effectiveness of interventions to manage type 1 diabetes in the U.S.

BACKGROUND: The CDC's Colorectal Cancer Control Program (CRCCP) partners with health system clinics to implement evidence-based interventions (EBIs) to increase colorectal cancer (CRC) screening prevalence. The sustainability of those EBIs is critical for the long-term success and impact of the CRCCP. This paper examines various aspects of the sustainability of these EBIs, including the factors associated with sustainability. METHOD: We used Clinic Data collected by CDC for program evaluation. The study employed two definitions of sustainability and conducted a comprehensive analysis including all available information on sustainability in the Clinic Data. Our descriptive analysis included comparing frequencies and means of the outcome variable as defined in the study. Logistic regression methods were used to explore the association of multiple explanatory factors with EBI sustainability. RESULTS: The results highlighted significant variations in the sustainability of different EBIs. Provider reminders were reported as sustainable by 82.0% of the clinics, while reducing structural barriers were reported as sustainable by 55.6% of the clinics. The percentage of clinics able to sustain each of the four EBIs trended upwards over time, ranging from 13 to 34 percentage points increase. Clinics that had implemented EBIs before CRCCP involvement, those that integrated multiple interventions, and those with dedicated screening champions were more likely to sustain EBIs in the long term. CONCLUSIONS: We found substantial improvement in the sustainability of EBIs over the 5-year program period, although results varied by EBIs and room for improvement remains. The findings offer valuable insights for future implementation and sustainability of EBIs.

INTRODUCTION: The antiretroviral therapy (ART) initiation policy in Uganda recommends that ART is initiated on the same day of HIV diagnosis to those who do not have contraindications. We assessed determinants of retention in ART care at the first follow-up (FFU) after same-day ART initiation and retention in long-term care beyond the FFU visit. METHODS: We conducted a retrospective longitudinal analysis among persons living with HIV aged ≥18 years who initiated ART during April 2016-February 2021 after the inception of Uganda's Test-and-Treat ART policy, which states that 'all individuals diagnosed with HIV should initiate ART regardless of clinical stage CD4 count'. Missing the FFU after ART initiation (missing FFU) was defined as not returning for FFU within 1 month of ART initiation; loss to follow-up long-term (LTFU-LT) was defined as delaying more than 3 months to return for a scheduled ART drug refill after the FFU appointment. LTFU-LT time was defined as the time from the FFU visit date to the last follow-up visit date during the study period. We used log-binomial distributions to estimate unadjusted and adjusted relative risks (adjRRs) of missing FFU, and we used Cox proportional hazard models to estimate unadjusted and adjusted hazard ratios (adjHRs) for LTFU-LT. RESULTS: Overall, 8332 clients initiated ART on the same day of HIV diagnosis. Most were female (55%), aged 25-34 years (44%), resided in the semi-urban or rural district (41% and 41%, respectively) and had a median age of 25 years (IQR = 24-35). Overall, missing FFU was 15.1%. Increased likelihood/risk of missing FFU was seen in clients who initiated ART at outreach health service centres versus health facilities (adjRRs = 1.79, 95% CI = 1.6-2.0), in younger clients aged 18-24 years and 25-34 years versus ≥45 years [(adjRRs = 1.65, 95% CI = 1.3-2.0) and (adjRRs = 1.31, 95% CI = 1.1-1.6), respectively], and clients residing in agrarian districts versus fishing districts (adjRRs = 1.24, 95% CI = 1.1-1.4). Overall, the LTFU-LT rate was 25 clients/100 pys (95% CI = 23.9-25.9) and was associated with younger age (18-34 years versus ≥45 years, adjHRs = 1.77, 95% CI = 1.5-2.1), residence in semi-urban (adjHRs = 1.33, 95% CI = 1.2-1.5) or agrarian district (adjHRs = 1.30, 95% CI = 1.2-1.5) versus fishing-community district. CONCLUSION: Retention-strengthening strategies in tandem with same-day ART initiation efforts for younger clients and clients initiated on ART from mobile and outreach health service settings might improve HIV treatment retention. Best practices for retaining fishing-community clients might improve health outcomes if applied to agrarian and semi-urban communities.

IMPORTANCE: West Nile virus (WNV), a neurotropic flavivirus spread by Culex species mosquitoes, is the leading cause of mosquito-borne disease in the contiguous US. From 2014 to 2023, a mean of 1298 WNV neuroinvasive disease cases and 129 deaths were reported annually in the US. OBSERVATIONS: Almost all WNV infection occurs via mosquito bites, but transmission can rarely occur via blood transfusion, organ transplantation, and transplacental, perinatal, breastmilk, percutaneous, and conjunctival exposure. Since 2018, large WNV outbreaks have been reported in Europe, Tunisia, Israel, and the US. In 2021, the largest county-level US outbreak occurred in Arizona, with 1487 disease cases and 101 deaths reported. Based on seroprevalence surveys, approximately 80% of human WNV infections are asymptomatic, 20% cause a febrile illness (West Nile fever), and less than 1% cause neuroinvasive disease (eg, meningitis, encephalitis, acute flaccid myelitis). Mortality of patients with neuroinvasive disease is approximately 10% overall but is 20% in individuals 70 years or older and 30% to 40% in patients with hematologic malignancies, solid organ transplants, and those receiving B-cell-depleting monoclonal antibodies. Among patients hospitalized for WNV disease, 30% to 40% are discharged to long-term care facilities, and more than 50% have long-term sequelae such as fatigue, weakness, myalgia, memory loss, and depression. WNV transmission during solid organ transplantation was identified in 14 clusters in the US and Italy from 2002 to 2023. Since WNV screening of the US blood supply began in 2003, 14 cases of WNV transmission through blood transfusion have been reported. For patients with fever or neurologic symptoms during summer and fall months, WNV should be considered; IgM testing of serum and/or cerebrospinal fluid is recommended, followed by confirmatory neutralizing antibody testing in cases of possible exposure to cross-reacting flaviviruses, atypical presentation or death, or suspected unusual transmission modes such as organ transplantation. Reverse transcription-polymerase chain reaction testing is often more sensitive than IgM testing in patients with severe immunocompromise. There are no evidence-based therapies or human vaccines for WNV disease. Preventive methods include personal protective behaviors, such as using Environmental Protection Agency-registered mosquito repellents, wearing protective clothing, and limiting outdoor exposure from dusk to dawn, and community mosquito control measures. CONCLUSIONS AND RELEVANCE: WNV causes more than 1200 neuroinvasive disease cases and 120 deaths annually in the US. People who are older or immunocompromised are at higher risk of severe disease and death. Since there are no therapies or human vaccines, prevention relies on personal protective measures, WNV surveillance, and mosquito control interventions.

Gay, bisexual, and other men who have sex with men (MSM) are disproportionately affected by HIV infection in the United States, especially Black MSM (BMSM) and Hispanic/Latino MSM (HLMSM). Long-acting preexposure prophylaxis (LA PrEP) is effective in preventing HIV; however, medical mistrust may contribute to barriers in uptake among BMSM and HLMSM. We assessed the role of medical mistrust in BMSM and HLMSM's unwillingness to use LA PrEP. BMSM and HLMSM aged ≥18 years without a previous HIV diagnosis or current PrEP use were recruited through dating and general interest websites/apps. Using Poisson regression with robust standard errors, we conducted multivariate analyses to assess the association between medical mistrust and willingness to use LA PrEP (i.e., injection or rod implanted in the arm) separately for each racial/ethnic group. Over 90% of the 1,126 BMSM and 924 HLMSM in this study were willing to use some form of PrEP; however, only 74% of BMSM and 81% of HLMSM were willing to use PrEP injections, and significantly fewer BMSM (30%) were willing to receive a PrEP implant compared with 44% of HLMSM. After controlling for sociodemographic, behavioral, and clinical covariates, medical mistrust was associated with lower willingness to use LA PrEP for BMSM, but not for HLMSM. Addressing and reducing medical mistrust among BMSM is important to increase the use of LA PrEP as an effective HIV prevention strategy. Addressing structural barriers and building trust within healthcare systems are crucial steps in reducing disparities in HIV infection among BMSM and HLMSM.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are persistent organic pollutants, many of which exhibit low in vivo clearance rates. The long-chain PFAS (≥6 perfluorinated carbons), due to low clearance rates, are often perceived to exert a higher toll on human health than short-chain PFAS. However, a comprehensive toxicological and epidemiological comparison of long- and short-chain PFAS is overdue, leaving significant data gaps and limitations. For the first time, this study investigated the quantitative relationship between overall PFAS fluorine structure (C-F bond), which includes the alkyl chain length as one component, and PFAS doses that trigger changes in rat blood-based clinical markers. Fifteen markers published by the National Toxicology Program (NTP) after 28-day exposure to 7 PFAS with both long- and short-chain perfluorinated alkyl structures were examined. The aim of this study was to (1) determine PFAS doses that trigger changes in the marker levels for hepatic, renal, cardiovascular, and metabolic systems and (2) use these doses in multiple linear regression models to examine relationship to variables describing PFAS chemical structures. Our findings showed a log-linear dependence of alterations in marker levels on PFAS fluorine structure, as measured in the number of alkyl carbon-fluorine (C-F) bonds. Each C-F bond affected the marker effect levels by 0.45 ± 0.01 mmol/kg-day. The variety of studied clinical markers suggests that PFAS exposures led to deviations in multiple biological pathways in the rat animal model, which may inform future research and regulatory decisions. | Perfluorinated carboxylic or sulfonic acids with linear chains of 4 to 10 carbons, known as perfluoroalkyl acids (PFAA)s, are types of PFAS commonly found in the environment.In a 28-day study by NTP, these PFAAs had dose-response effects in a panel of blood-based clinical markers in rats at specific doses.In regression models for individual clinical markers or a joint regression for all markers, these doses were strongly correlated with the number of carbon-fluorine bonds in the PFAAs.The resulting multiple linear regression (MLR) models provide a simple estimation tool for PFAAs’ exposure levels on blood-based clinical marker responses in rats. | eng

INTRODUCTION: Gulf War Illness is a chronic multisymptomatic disorder that affects as many as 25-35% of the military personnel who were sent to the Persian Gulf war in 1991. The illness has many debilitating symptoms, including cognitive problems, gastrointestinal symptoms, and musculoskeletal pain. Those so afflicted have been sick for more than 30 years and, therefore, it has become imperative to understand the etiology of Gulf War Illness and then produce treatments to ease the symptoms. We hypothesized that the length of the disease was reflected in epigenetic modification of possibly several genes related to the symptoms. METHODS: We subjected male and female mice from 11 BXD strains to combined corticosterone and the sarin surrogate, diisopropylfluorophosphate, to emulate the physiological stress of war and the potential exposures to organophosphate pesticides and nerve agent in theater. Three hundred days after treatment, we used Methyl-CpG-binding domain sequencing (MBD-seq) to assay genome-wide methylation. RESULTS: The analysis revealed 20 methylated genes, notably Eif2b5, that regulates myelin production. DISCUSSION: Loss of myelin with accompanying musculoskeletal pain is a major symptom of Gulf War Illness. Our work demonstrates multiple genes were methylated by exposure to organophosphates and glucocorticoids. These genes point to biochemical mechanisms that may be targets for therapeutic intervention.

INTRODUCTION: We examined the association of pre-exposure prophylaxis (PrEP) programme retention with the use of daily, event-driven (ED) or regimen switching reported during follow-up at any point prior to discontinuation among men who have sex with men (MSM) in Hanoi, Vietnam. METHODS: Between April 2020 and February 2023, we collected data from PrEP clients at Hanoi Medical University Sexual Health Promotion clinic who were prescribed either ED or daily PrEP at the initial visit; at subsequent visits, clients reported the regimen used since the prior visit. We defined three categories of PrEP use: ED-PrEP exclusively, daily PrEP exclusively and switching regimens. The primary outcome was time to discontinuation in the PrEP programme during the study period, defined as missing a scheduled visit by > 30 days. We performed survival analysis using Kaplan-Meier curves. RESULTS: In total, 2107 people were included: 61.1% (n = 1288) reported exclusive use of daily PrEP, 10.4% (n = 220) reported exclusive use of ED-PrEP and 28.4% (n = 599) reported switching PrEP regimens. Among switchers, 29.40% (n = 176) switched more than once. Furthermore, 82.5% switched from daily to ED-PrEP and 17.5% switched from ED to daily PrEP. The median time to discontinuation in the PrEP programme was 105 days (IQR: 52-182) among those reporting exclusive use of ED-PrEP, 104 days (IQR: 56-274) among those reporting exclusive use of daily PrEP and 163 days (IQR: 101-308) among those who switched. Among switchers, those who switched more than once had a median time to discontinuation in the PrEP programme of 231 days (IQR: 137-380) in comparison to 133 days (IQR: 90-274) for those who switched once. CONCLUSIONS: We provide real-world data from MSM in an HIV PrEP programme in Vietnam that those who switched had longer periods of retention during the study period. Our findings suggest that offering flexible PrEP regimen options may improve engagement and long-term adherence among this population.

OBJECTIVES: Understanding of long-term lung cancer risks from radon decay products (RDP) exposure derives largely from studies of uranium miners. We aimed to compare mortality for lung and other cancers to the general population, to estimate excess absolute rate (EAR) and excess relative rate (ERR) from RDP exposure, and to estimate the joint effects of RDP and cigarette smoking in extended follow-up of a cohort of 4137 male uranium miners from the US Colorado Plateau. METHODS: We extended mortality follow-up through 2016 and re-evaluated RDP exposure against original work history and mine records. We calculated standardised mortality ratios (SMRs) compared with a regional population, evaluated EAR of lung cancer mortality using standardised rate ratios and modelled ERR using Cox proportional hazards regression. We evaluated interactions of RDP with smoking pack-years, attained age (AA) and time-since-exposure (TSE). RESULTS: There were 695 lung cancer deaths, including 146 among never-smokers and light smokers. The overall SMR was >4; the EAR per unit RDP exposure increased substantially with smoking pack-years and decades of follow-up. Lung cancer ERR decreased with AA and TSE. ERR attenuation at high exposure rates was smaller than observed elsewhere. Joint effects of RDP and smoking were submultiplicative but greater-than-additive, appearing closer to multiplicative at lower RDP exposures. Pancreas was the only other site showing a significantly positive ERR per unit exposure. CONCLUSIONS: Excess rates of lung cancer mortality persist throughout the lifespan among this cohort of uranium miners. Information about RDP-smoking interactions is of interest for occupational and general population exposure.

Attractive targeted sugar baits (ATSBs) are a novel malaria control tool designed to target mosquitoes outdoors. We conducted a cluster-randomised trial to evaluate the impact of ATSBs on malaria indicators in Kenya. Seventy clusters (≥100 households/cluster) in Siaya county were randomly assigned (1:1) to intervention or control. Pyrethroid-only long-lasting insecticidal nets were distributed to all clusters, aiming for universal coverage. Two ATSBs containing dinotefuran were hung outside household structures in intervention clusters. ATSBs were monitored every two months and replaced every six months over two years. Three consecutive cohorts of randomly selected children (1- < 15 years) were enrolled, aiming to accrue 1,260 person-years over two years of follow-up. Incidence of clinical malaria (fever with a positive malaria test) was the primary outcome. A multilevel Poisson regression model was applied, with clusters as a random intercept and study arm as a fixed effect. Secondary outcomes were malaria prevalence in community residents (≥1 month), and parity of mosquitos captured through human landing catches. In March 2022, ATSBs were delivered to 33,180 of 33,419 (99.3%) household structures in intervention clusters. Overall, 268,268 ATSBs were deployed over two years. Of 2,962 cohort children enrolled (intervention = 1,497; control = 1,465), 2,869 (96.9%) were included in the primary analysis (intervention = 1,461; control = 1,408), contributing 1,445 person-years of follow-up. Malaria incidence was 1.32 episodes per person-years in the intervention arm versus 1.20 in the control (unadjusted incidence rate ratio 1.11; 95% CI: 0.75-1.65; p = 0.598). Of 7,488 community residents surveyed (intervention = 3,760; control = 3,728), 1,474 (39.2%) intervention and 1,461 (39.2%) control participants tested positive for malaria (unadjusted odds ratio [OR] 0.98; 95% CI: 0.60-1.59; p = 0.93). Of 6,457 female anopheles mosquitoes collected (intervention = 4,058; control = 2,399), 3,579 (88.2%) intervention and 1,973 (82.2%) control mosquitoes were parous (OR 1.34; 95% CI: 0.91-1.99; p = 0.14). In Kenya, we found no evidence that ATSBs reduced clinical malaria incidence, malaria prevalence, or vector parity. Trial registration Clinicaltrials.gov (NCT05219565), 22 January 2022.

West Nile virus (WNV) causes thousands of arboviral infections in the United States each year. Patients with immune-compromising conditions and elderly people are at higher risk of severe WNV neuroinvasive disease (WNND). Despite its broad endemicity nationwide, no U.S. Food and Drug Administration-approved vaccine or therapeutic treatments exist. We summarized existing peer-reviewed literature on the preclinical development of monoclonal antibody (MAb) prophylaxis and therapeutics for the prevention and treatment of WNND. Five bibliographical databases (CINAHL, Cochrane Library, Embase, MEDLINE, and Scopus) were searched for applicable research studies performed from 1 January 1998 to 1 May 2025. In total, 2347 titles and abstracts were screened, 263 full-text publications reviewed, and 25 studies included. Studies included detailed preclinical development and evaluations of MAbs targeting the envelope (E) protein (n = 13), other viral proteins (n = 3), flaviviral cross-protective monoclonal antibodies (n = 4), and novel antibody configurations or delivery methods (n = 5). The most well-studied MAb, E16, targeting E- Domain III (E-DIII), was effective at inhibiting and treating WNND in experimental animal models. No work investigated ways to traffic therapeutic antibodies across the blood-brain barrier. This review summarizes the current research in the development of monoclonal antibody therapeutics for WNV and addresses gaps in the knowledge for future consideration.

Addressing antimicrobial resistance requires multi-disciplinary action, including from the clinical laboratory. Cascade reporting of the antimicrobial susceptibility test (AST) is a strategy used by some laboratories to nudge clinicians toward the use of more narrow-spectrum antimicrobials. Cascade reporting involves suppression of broader-spectrum antimicrobials if the narrower-spectrum first-line antimicrobials show in-vitro susceptibility. Studies have shown that cascade reporting can reduce use of broad-spectrum antimicrobials and reduce antimicrobial resistance rates. However, implementing cascade reporting can be complex, and some question the effectiveness on impacting long-term prescribing behaviors. Furthermore, there are concerns surrounding compliance and the possible negative impact on public health surveillance for antimicrobial resistance. In this article, experts weigh in on the benefits and risks associated with implementing AST cascade reporting. General consensus is that cascade reporting is a benefit to antimicrobial stewardship, but protocols need careful implementation to minimize risk to patients and public health.

BACKGROUND: Tuberculosis (TB) preventive treatment (TPT) is critical to the end TB strategy. There is limited evidence on its long-term protective effect among people living with HIV (PLWH) receiving antiretroviral therapy (ART) in high-burden programmatic settings. METHODS: This observational cohort study included PLWH who initiated a single TPT course from March 2017 to September 2018 at 14 ART centres in Andhra Pradesh, India (TB prevalence: 274/100,000). We followed PLWH for 6 years and censored person-time at TB diagnosis, loss to follow-up, or death. We calculated TB incidence rates (IR) and mortality rates (MR) per 100 person-years (PY) stratified by TPT completion and effective ART (viral load<1000 copies/ml). Cox-proportional hazards models estimated adjusted hazard ratios (aHR) with 95% confidence limits (95% CL) for TB and mortality. FINDINGS: We followed 4,706 PLWH for 23,414 PY. TB was diagnosed in 135 PLWH (2.9%)-122 among 4,454 PLWH who completed TPT (IR: 0.55/100PY, 95% CL: 0.46-0.66), and 13 among 252 PLWH who did not (IR: 1.06/100PY, 95% CL: 0.56-1.81). There were 553 all-cause deaths (11.8%)-MR: 2.2/100PY (95% CL: 2.0-2.4) among those who completed TPT compared to 13.5/100PY (95% CL: 11.1-16.3) among those who did not. TPT, combined with effective ART, was associated with an 87% reduction in TB (aHR: 0.13; 95% CL: 0.05-0.37) and a 94% reduction in all-cause mortality (aHR: 0.06; 95% CL: 0.04-0.10). CONCLUSION: A single TPT course combined with effective ART conferred durable protection against TB and significantly reduced mortality among PLWH in a high-burden TB setting.

Background: Antifungal therapeutic drug monitoring (TDM) is critical for individualized, precision treatment and prevention of fungal infections, but previous research has highlighted low TDM utilization rates, potentially reflecting long turnaround times, complex testing logistics, results interpretation, and cost. Objectives: To inform strategies to increase antifungal TDM use, we assessed TDM-related knowledge, attitudes, and practices among infectious disease (ID) physicians and pharmacists. Methods: We summarized findings from three structured focus group discussions (FGD)—two with six ID physicians each and one with six pharmacists—during March 2024. Open-ended discussions were held regarding awareness of and experiences with fungal infections and TDM, perceptions of antifungal TDM such as potential benefits, barriers, and challenges to conducting antifungal TDM, and information needs about antifungal TDM. We conducted qualitative transcription-based analysis to identify themes. Results: Six themes emerged from FGDs: (1) variable knowledge and experience with antifungal TDM among participants, (2) the importance of close collaboration between physicians and pharmacists during the TDM process, (3) the main motivators driving TDM use were improving treatment outcomes, preventing toxicity, and addressing pharmacokinetic variability, (4) the perception that antifungal resistance was unrelated to TDM, (5) key barriers were a lack of comprehensive clinical guidelines, long lab testing turnaround times, complex testing logistics, and high costs, and (6) a need for additional clinical data on TDM's impact on outcomes. Conclusions: Our findings can inform efforts to increase TDM use by addressing barriers to practice. Development of evidence-based clinical guidelines and improvements in testing infrastructure across practice settings could increase antifungal TDM use. Published 2025. This article is a U.S. Government work and is in the public domain in the USA.

BACKGROUND: School professionals, including classroom teachers, school administrators, psychologists, teachers' aides, and nurses, often interact with students with concussions. To ensure they have the knowledge to identify and manage concussions, the U.S. Centers of Disease Control and Prevention developed the HEADS UP to Schools online training. METHODS: The HEADS UP to Schools training includes a pre-test and post-test consisting of 16 knowledge questions in three areas (symptom recognition, school support and accommodation, and guidance and recommendations for school staff) and five self-efficacy questions. Pre- and post-test responses of 8750 individuals were compared and analyzed to evaluate the effectiveness of the training. RESULTS: Respondent scores significantly improved between pre- and post-test responses for all knowledge questions and self-efficacy questions. IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: Schools and school districts may consider offering this training to staff to help ensure that at least one person at each school is trained on concussion and to increase awareness of evidence-based practices. CONCLUSIONS: Knowledge and self-efficacy on concussion identification and management improved among school professionals who completed the HEADS UP to Schools training. Future research to assess whether concussion knowledge and self-efficacy are maintained long term may be beneficial.

BACKGROUND: Training and education may benefit nurses whose nonstandard work hours put them at risk of poor sleep, fatigue, and ensuing adverse health and safety outcomes. The National Institute for Occupational Safety and Health (NIOSH) published "Training for Nurses on Shift Work and Long Work Hours" in 2015 as a free online resource which remains one of the few trainings available on this topic. However, the extent to which nurses have completed the program and the characteristics of current learners have not been examined. OBJECTIVE: We aimed to describe the potential reach of the NIOSH Training for Nurses between May 2015 through December 2020. METHODS: Data were obtained on learners who received continuing education credits upon completion of the NIOSH Training for Nurses. We applied a widely used implementation and evaluation framework, RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance), to describe the potential reach of the nurses' training and provide descriptive statistics of learners. RESULTS: From 2015 to 2020, 7899 learners from different occupations received continuing education credits for completing the training. Approximately 60% of learners were nurses and 30% were students. Among nurses, most were Registered Nurses (93%), with few Licensed Practical Nurses (6%) and Advanced Practice Nurses (2%). In 2020, the number of learners who were nurses represented only 0.09% of all licensed US nurses. CONCLUSION: A renewed dissemination plan may help extend training reach to the larger population of licensed US nurses. The NIOSH training remains a seminal, freely available, online resource for nurses, filling a critical gap in training to manage work-related fatigue.

INTRODUCTION: Urinary biomarkers are useful in characterizing exposure to harmful and potentially harmful constituents (HPHCs) of tobacco products and linking exposure to health outcomes. However, the consistency/reproducibility of many urinary biomarkers over long periods is unknown. METHODS: Among people who exclusively used cigarettes in the Population Assessment of Tobacco and Health Study Waves 1, 2, 4, and 5 (ranging from 746 to 1361 subjects), we used weighted models to estimate variance components and intra-class correlation coefficients (ICC) for 15 biomarkers of exposure for urine samples collected 3-5 years apart, creatinine-only-adjusted and also adjusted for demographic and behavioral predictors. RESULTS: In models adjusted only for creatinine, ICC values of biomarkers ranged from 0.41 (95% confidence interval (CI): 0.32, 0.49) (N-acetyl-S-(2-carbamoylethyl)-L-cysteine) to 0.73 (95% CI: 0.65, 0.81) (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol), varying within each chemical class. For models adjusted for predictors, associations between biomarkers and predictors were similar for samples collected 3-5 years and 1 year apart. Predictor-adjusted ICCs for samples collected 3-5 years apart ranged from 0.29 (95% CI: 0.17, 0.40) (N-Acetyl-S-(2-carbamoylethyl)-L-cysteine) to 0.63 (95% CI: 0.56, 0.69) (N-Acetyl-S-(2-hydroxyethyl)-L-cysteine) and appeared not different from those for samples collected 1 year apart. CONCLUSIONS: Even for 3 or 5 years between urine sample collection, unadjusted biomarkers of exposure showed fair to excellent reproducibility. Similar consistency between 1 year and 3-5 years between collections was found when including predictors in the model. IMPLICATIONS: These biomarkers may be useful to characterize long-term exposures to HPHCs from cigarettes with different characteristics for those who smoke cigarettes exclusively.

BACKGROUND: Comparing the characteristics of patients with long COVID to those with other post-acute infection syndromes (PAIS) could potentially provide clues to common underlying disease processes that may affect patient recovery. METHODS: We identified records of patients who had documented SARS-CoV-2 tests in the University of Washington Medicine electronic health record (EHR) database from January 1, 2019, through January 31, 2022 (n = 139,472). Patients were classified into three groups: 1) long COVID defined by a positive SARS-CoV-2 test and a long COVID-related diagnosis code (n = 580); 2) recovered COVID defined by a positive test and no long COVID associated diagnosis codes (n = 7,437); and 3) non-COVID PAIS defined by a negative test, non-SARS-CoV-2 related PAIS diagnosis codes, and no COVID related codes (n = 106). Using multivariate logistic regression, we compared the clinical characteristics of these groups at three timeframes to address preclinical, acute and post-acute diagnoses: before index SARS-CoV-2 test, within 30 days of index test, and > 30 days after index test. RESULTS: The long COVID group had a higher Charlson comorbidity index [median (IQR), 2 (0-4)] than the other two patient groups [median (IQR), 1 (0-3) and 1 (0-3)]. The long COVID and non-COVID PAIS patients were older and had greater smoking exposure than the recovered COVID group. Compared to the recovered COVID control group, the long COVID group had more health problems prior to the infection, including respiratory and metabolic as well as more severe infections and comorbidities based on the ICD codes found in the acute phase records. In the post-acute timeframe, many symptoms were more likely to be associated with long COVID than recovered patients with COVID-19 including abnormalities of heart beat [OR (95% CI), 5.31 (3.96-7.13)], cognition, perception, or emotional state symptoms [OR (95% CI), 5.14 (3.81-6.92)], malaise and fatigue [OR (95% CI), 4.20 (3.13-5.63)], and sleep disorders [OR (95% CI), 2.47, (1.79-3.43)], all p < 0.05. In contrast, the non-COVID PAIS group shared many similarities with the long COVID group across all three timeframes. CONCLUSIONS: Patients diagnosed with long COVID were more similar to patients with a non-COVID-related PAIS than to recovered patients with COVID-19. This suggests risk factors for PAIS may be similar and independent of the infectious agent.

INTRODUCTION: Prior research has observed increased risks for numerous chronic conditions among individuals with Long COVID. Chronic conditions have been associated with employment limitations and increased economic hardships. Data from the Behavioral Risk Factor Surveillance System (BRFSS) present an opportunity to examine changes by employment status in the prevalence of a range of chronic conditions between 2019 (pre-pandemic) and, in 2022, by self-reported COVID-19 or Long COVID. METHODS: We assessed the prevalence of chronic conditions in 2022 by employment status and self-reported COVID-19 and Long COVID history using data from BRFSS for adults of prime working age (25-54 years) who were employed for wages, self-employed, unemployed less than 1 year, unemployed 1 year or more, or unable to work. For each chronic condition (coronary heart disease and myocardial infarction [combined], stroke, ever and current asthma, chronic obstructive pulmonary disease, kidney disease, diabetes, and arthritis), we generated adjusted prevalence ratios (aPRs) comparing 2022 prevalence by COVID-19/Long COVID category to prevalences among respondents in that employment status before the pandemic (2019). RESULTS: The prevalence of both asthma and diabetes increased significantly between 2019 and 2022 among respondents in all included employment categories and COVID-19/Long COVID histories combined. Among employed respondents with Long COVID in 2022, aPRs using 2019 prevalence figures for all employed respondents as a baseline for comparison had statistically significant elevations for every chronic condition assessed. CONCLUSIONS: The increased prevalence of a range of chronic conditions between 2019 and 2022 among adults with Long COVID may present a burden for individuals, the workplace, the healthcare system, and the economy. Additional research in a longitudinal context could better quantify these associations. Efforts to prevent, identify, and treat Long COVID can reduce this burden.

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.

We conducted retrospective analysis of the emergence of the SARS-CoV-2 JN.1 variant in US wastewater during November 2023-July 2024 using Aquascope, a bioinformatics pipeline for the National Wastewater Surveillance System. This study highlights the value of open-source bioinformatics tools in tracking pathogen variants for public health monitoring.

BACKGROUND: Hypertension is a major risk factor for cardiovascular and renal diseases, significantly contributing to morbidity and mortality. The COVID-19 pandemic has heightened concerns about the impact of hypertension on severe COVID-19 outcomes. METHODS: We analyzed 2020-2021 data from the MarketScan Commercial and Health and Productivity Management databases, focusing on adults aged 18-64 years with continuous employer-sponsored private insurance, excluding pregnancy or capitated plans. We compared medical costs, healthcare utilization (emergency department [ED] visits, inpatient admissions, outpatient visits, and outpatient prescription drugs), and productivity losses (sick absences, short-term disability [STD], and long-term disability [LTD]) between individuals with and without hypertension, stratified by COVID-19 diagnosis. We used multivariable regression models, including an interaction term for hypertension and COVID-19 diagnosis, to estimate differences in outcomes, adjusting for demographics and comorbidities. RESULTS: Among 1,296,596 adults, 21% had hypertension. Those with hypertension were older, less likely female, less likely urban residents, and had more comorbidities. Excess medical costs associated with hypertension were $8,572 per patient over the two-year period (95% CI $8,182-$8,962). Patients with versus without hypertension had 0.200 (95% CI, 0.195-0.205) more ED visits, 0.081 (95% CI, 0.077-0.085) more inpatient admissions, 5.984 (95% CI, 5.892-6.075) more outpatient visits, and 20.25 (95% CI, 20.09-20.41) more prescriptions per patient over the two-year period. They also had more sick absences (1.13 days; 95% CI 0.93-1.34) and STD occurrences (3.88 days; 95% CI 3.56-4.20) per patient. Among those with hypertension, individuals with versus without COVID-19 had $3,495 (95% CI, $2,135-$4,856) higher medical costs and 2.588 (95% CI, 1.112-4.065) more STD days per patient over the two-year period. CONCLUSIONS: Hypertension was associated with higher medical costs, healthcare utilization, and productivity losses, exacerbated by COVID-19.

For detection of viral RNA in blood or tissue, samples are often collected into lysis buffers prior to downstream molecular analysis. Immediate sample processing and cold storage are not always possible during large-scale or field studies, or in facilities lacking a stable electrical supply. Additionally, samples may need to be transported significant distances before processing. Here, using Peptidylprolyl Isomerase A (Ppia), a stably expressed gene in rodent tissues, we investigate the long-term stability and detection of RNA in guinea pig tissues stored for up to 52 weeks and in hamster blood stored for up to 12 weeks in MagMAX Lysis/Binding Solution Concentrate at -80°C, 4°C, 21°C, and 32°C.

Nonoccupational postexposure prophylaxis (nPEP) for HIV is recommended when a nonoccupational (e.g., sexual, needle, or other) exposure to nonintact skin or mucous membranes that presents a substantial risk for HIV transmission has occurred, and the source has HIV without sustained viral suppression or their viral suppression information is not known. A rapid HIV test (also referred to as point-of-care) or laboratory-based antigen/antibody combination HIV test is recommended before nPEP initiation. Health care professionals should ensure the first dose of nPEP is provided as soon as possible, and ideally within 24 hours, but no later than 72 hours after exposure. The initial nPEP dose should not be delayed due to pending results of any laboratory-based testing, and the recommended length of nPEP course is 28 days. The recommendations in these guidelines update the 2016 nPEP guidelines (CDC. Updated guidelines for antiretroviral postexposure prophylaxis after sexual, injection drug use, or other nonoccupational exposure to HIV - United States, 2016. Atlanta, GA: US Department of Health and Human Services, CDC; 2017). These 2025 nPEP guidelines update recommendations and considerations for use of HIV nPEP in the United States to include newer antiretroviral (ARV) agents, updated nPEP indication considerations, and emerging nPEP implementation strategies. The guidelines also include considerations for testing and nPEP regimens for persons exposed who have received long-acting injectable ARVs in the past. Lastly, testing recommendations for persons who experienced sexual assault were updated to align with the most recent CDC sexually transmitted infection treatment guidelines. These guidelines are divided into two sections: Recommendations and CDC Guidance. The preferred regimens for most adults and adolescents are now bictegravir/emtricitabine/tenofovir alafenamide or dolutegravir plus (tenofovir alafenamide or tenofovir disoproxil fumarate) plus (emtricitabine or lamivudine). However, the regimen can be tailored to the clinical circumstances. Medical follow-up for persons prescribed nPEP also should be tailored to the clinical situation; recommended follow-up includes a visit at 24 hours (remote or in person) with a medical provider, and clinical follow-up 4-6 weeks and 12 weeks after exposure for laboratory testing. Persons initiating nPEP should be informed that pre-exposure prophylaxis for HIV (PrEP) can reduce their risk for acquiring HIV if they will have repeat or continuing exposure to HIV after the end of the nPEP course. Health care professionals should offer PrEP options to persons with ongoing indications for PrEP and create an nPEP-to-PrEP transition plan for persons who accept PrEP.

BACKGROUND: Phthalate exposures are ubiquitous and have been associated with pregnancy complications. Interaction between serum long-chain n-3 polyunsaturated fatty acids (n3PUFA) and phthalate biomarkers is biologically plausible because both can bind to human peroxisome proliferator-activated receptors (PPARs) which are involved in placenta development. However, evidence of this interaction in humans is lacking. OBJECTIVE: To evaluate whether serum n3PUFA modifies the associations of biomarkers of phthalate exposure on pregnancy outcomes. METHODS: Among 351 women undergoing in vitro fertilization in the Environment and Reproductive Health study (2004-2017), we evaluated the effect modification of eicosapentaenoic acid (EPA) and serum docosahexaenoic acid (DHA) on the association of pregnancy outcomes with the mixture of urinary concentrations of phthalate biomarkers by quantile g-computation. All models were adjusted for age, body mass index, prior smoking, infertility diagnosis, treatment year, and urinary specific gravity. RESULTS: Concentrations of the phthalate biomarkers mixture were associated with higher adjusted probabilities of pregnancy loss and lower estimated probabilities of live birth among women with serum EPA+DHA in the lowest tertile (< 2.66% of total fatty acids), but not among women with middle-to-high serum EPA+DHA (p interactions = 0.06 and 0.15, respectively). Among women in the lowest tertile of serum EPA+DHA, the adjusted probability [95% confidence interval (CI)] of pregnancy loss for women in the lowest and highest quartile of phthalates mixtures was 5% (2%, 16%) and 44% (23%, 85%), respectively (p trend = 0.01). The corresponding estimates were 14% (5%, 41%) and 11% (3%, 42%) among women with serum EPA+DHA in the highest tertile (⩾ 3.78% of total fatty acids) (p trend = 0.81). Similar trends were observed for live birth but not for implantation and clinical pregnancy. CONCLUSIONS: This study suggests adverse effects of phthalate exposure on pregnancy loss and live birth may be attenuated by intakes of n3PUFA. These results, if replicated, could inform clinical practice reducing the burden of infertility by phthalate exposure among the general population and improving pregnancy outcomes among subfertile couples.. https://doi.org/10.1289/EHP15942.

Rocky Mountain spotted fever (RMSF) is a deadly tick-borne disease caused by the bacterium Rickettsia rickettsii. An ongoing epidemic of RMSF is affecting tribal communities in Arizona, with nearly 500 cases and 28 deaths since 2003. The San Carlos Apache Tribe has been consistently working to prevent RMSF using tick collars on dogs, pesticide treatments around homes, and increasing education for nearly a decade. Besides monitoring human disease levels and tick burden on dogs, we have little understanding of the long-term impact of prevention practices on tick abundance and infection rates in the peridomestic environment. We evaluated risk factors associated for tick infestation at home sites across the San Carlos Indian Reservation as well as R. rickettsii and Rickettsia massiliae prevalence in off-host ticks. Although the presence of fencing appears protective, the number of nearby structures is the most important risk factor associated with increased adult and nymphal tick abundance, highlighting the impact of a free-roaming dog population.

BACKGROUND: The Michigan Polybrominated Biphenyl (PBB) registry, followed since 1976, was created after a 1973 chemical manufacturing mistake. The flame retardant PBB was accidentally mixed into animal feed and distributed to Michigan farms for nearly a year, exposing farm residents and animal product consumers. OBJECTIVE: We synthesize knowledge to date on health effects of PBB exposure within the Michigan PBB Registry, and describe research findings in the context of literature on other persistent organic pollutants (POPs) and endocrine disrupting chemicals (EDCs). METHODS: We reviewed literature published from 1973-2025 on human health effects of PBB following the Michigan contamination using PubMed and Thompson Reuters (ISI) Web of Science databases. We excluded studies not in English; on exposures besides PBB; animal studies; reviews, abstracts, or letters to the editor; studies without a health outcome; and studies outside of Michigan or unrelated to the 1973 contamination. For each article, two researchers performed title and abstract screening, full article review, and data extraction. RESULTS: We included 79 publications out of 601 identified and screened. Early studies did not find many health outcomes associated with PBB, possibly because of methodological limitations. More recent studies on long-term and multigenerational impacts found an increased breast cancer risk, accelerated pubertal development and earlier menarche for girls exposed in utero, urogenital problems and slower pubertal development in boys exposed in utero, lower estrone 3-glucuronide and follicle-stimulating hormone among women exposed in childhood, and increased miscarriage risk among daughters of exposed women. Epigenetic and metabolomic research reported altered pathways related to estrogenic effects and immune function, and epigenetic alterations of spermatogenic cells. DISCUSSION: This unique community-academic partnership has produced insights into multigenerational consequences of EDC/POP exposures across the lifecourse. The findings from this cohort underscore the broader relevance of critical windows of vulnerability, particularly during fetal development and childhood.. https://doi.org/10.1289/EHP15012.

Genomic surveillance of SARS-CoV-2 is crucial for detecting emerging variants and informing public health responses. Various sequencing technologies are used for whole genome sequencing of SARS-CoV-2. This cross-platform benchmark study applied established bioinformatics tools to assess and improve the performance of Illumina NovaSeq, Oxford Nanopore Technologies MinION, and Pacific Biosciences Sequel II sequencing platforms in identifying SARS-CoV-2 variants and lineage assignment. NovaSeq produced the highest number of reads and bases, depth of coverage, completeness of consensus genomes, stable mapping coverage across open reading frames in the genome, and consistent lineage assignments. The long-read sequencing platforms had lower yields, sequencing depth, and mapping coverage, limiting the number of qualified sequences for lineage assignment and variant identification. However, implementing proper quality controls on sequence data overcame these limitations and achieved consistent SARS-CoV-2 lineage assignments across all three sequencing platforms. The advancements in library preparation and technology for long-read sequencing are likely to enhance sequence quality and expand genome coverage, effectively addressing current limitations in genome analysis. By merging the unique advantages of both short- and long-read methods, we can significantly improve SARS-CoV-2 genomic surveillance and provide insights into sequencing strategies for other RNA viruses, pending further validation. This may lead to precise tracking of viral evolution and support public health policy decisions.