Unmeasured confounding is a major concern in many epidemiologic studies that are not randomized. Negative control methods can detect and reduce confounding by leveraging the proxies of the unmeasured confounders, including negative control outcomes (NCO) and exposures (NCE). An NCO is presumably unaffected by the exposure of interest but would be associated with unmeasured confounders; an NCE presumably does not affect the outcome of interest but would be associated with unmeasured confounders. A recently proposed double negative control method leverages both NCO and NCE for unmeasured confounding bias. To demonstrate this relatively new methodology in pharmacoepidemiologic studies, we re-analyzed data from a prior safety study of Recombinant Zoster Vaccine (RZV). The prior study compared risk of safety outcomes of RZV versus unvaccinated comparators, using logistic regression with propensity score adjustment. We identified NCOs and NCEs that could be used to adjust for unmeasured confounding bias that could arise if RZV recipients are incomparable to the comparators due to unmeasured factors. The double negative control analysis yielded relative risk estimates slightly closer to 1.0 than those reported previously, providing additional evidence of RZV safety that is less vulnerable to unmeasured confounding.

PURPOSE: To investigate differences in teen-reported and parent-reported lifetime prevalence estimates of traumatic brain injury (TBI) symptoms, TBI evaluation, and TBI diagnosis among a nationally representative sample of teenagers aged 12-17 years old and their parents. METHODS: Parent-reported data from the 2021 to 2022 National Health Interview Survey linked with teen-reported data from the National Health Interview Survey-Teen July 2021-December 2022 (n = 1,153) were analyzed. Lifetime prevalence estimates for TBI symptoms (e.g., selected symptoms as a result of a blow or jolt to the head), history of evaluation by health professional for TBI (i.e., TBI evaluation), and TBI diagnosis stratified by sociodemographic characteristics and reporter type were produced, and z-tests were conducted to test for differences. Concordance measures were calculated to assess agreement between teen and parent survey responses to TBI measures. RESULTS: Lifetime prevalence of TBI symptoms varied by reporter type across all sociodemographic characteristics with teen-report consistently producing higher estimates. Estimates of TBI evaluation varied by reporter type only among older teens, non-Hispanic teens, and teens who participated in sports; there was no difference for TBI diagnosis. Percent agreement between the 2 reporters ranged from 73% to 95%, prevalence-adjusted bias-adjusted kappa ranged from 0.45 to 0.90, and Cohen's kappa ranged from 0.22 to 0.63. DISCUSSION: There was general agreement for observable outcomes TBI evaluation and TBI diagnosis, but discordance existed in reports of TBI symptoms. These findings suggest that youth self-report of TBI symptoms may enhance surveillance efforts.

Reliable, validated diagnostic tests are critical for rabies control in animals and prevention in people. We present a performance assessment and updates to the LN34 real-time RT-PCR assay for rabies diagnosis in postmortem animal brain samples. In two U.S. laboratories during 2017 to 2022, routine used of the LN34 assay produced excellent diagnostic sensitivity (99.72% to 100%) and specificity (99.99% to 100%) compared to the direct fluorescence antibody test (DFA). Almost all (>90%) DFA indeterminate results caused by non-specific or atypical fluorescence were negative by LN34 testing, representing up to 111 cases where unnecessary post-exposure prophylaxis could be avoided. LN34 assay original primer sequences showed low sensitivity for some rare lyssaviruses. Increased primer concentration combined with new primer formulation showed improved performance for impacted lyssaviruses with no loss in performance across diverse rabies virus variants from clinical samples. The updated LN34 and internal control assays were combined into a single-well LN34 multiplexed (LN34M) format, run at half reagent volumes. The LN34M assay showed similar detection of rabies virus to the singleplexed assay with simplified assay set-up, lower cost, and improved quality controls.

BACKGROUND: Prolonged exposure to hyperoxia can lead to hyperoxic acute lung injury (HALI) in preterm neonates. Vitamin D (VitD) stimulates lung maturation and acts as an anti-inflammatory agent. Our objective was to determine if VitD provides a dose-dependent protective effect against HALI by reducing inflammatory cytokine expression and improving alveolarization and lung function in neonatal mice. METHODS: C57BL/6 mouse neonates were randomized and placed in room air or hyperoxic (85% O(2)) conditions for 6 days. Control, low (5 ng/neonate) and high (25 ng/neonate) doses of VitD were administered daily beginning at day 2 via oral gavage. Lung tissue was analyzed for edema, changes in pulmonary structure and function, and inflammatory cytokine expression. RESULTS: Neonatal mice treated with VitD in hyperoxic conditions had improved weight gain, reduced pulmonary edema and increased alveolar surface area compared to untreated pups in hyperoxia. No significant changes in cytokine expression were observed between untreated and VitD neonates. While changes in surfactant protein mRNA expression were impacted by hyperoxia and VitD administration, no significant changes in alveolar type II cell percentages were observed. At 3 weeks, mice in hyperoxia treated with VitD had greater lung compliance, diminished airway reactivity and improved weight gain. CONCLUSIONS: High dose VitD significantly limited harmful effects of HALI. These results suggest that supplementation of VitD to neonatal mice during hyperoxia exposure provides both short-term and long-term protective benefits against HALI.

Increased prescribing of antibiotics commonly used for respiratory infections, including azithromycin, ceftriaxone, and doxycycline was observed in nursing homes (NH) during the COVID-19 pandemic however antibiotic prescribing was not linked to resident diagnosis. Therefore, our objective was to characterize antibiotic prescribing in residents with SARS-CoV-2 infection in a large cohort of US NHs.We conducted a retrospective cohort study using PointClickCare (PCC) data containing longitudinal NH electronic health records. We included 4,891 NHs that reported ≥1 medication order/month from April 2020-November 2021. We identified the first onset of SARS-CoV-2 infection using ICD-10-CM diagnosis code U07.1. To validate the number of SARS-CoV-2 infections per facility captured in PCC, we compared the total number of SARS-CoV-2 infections documented in PCC to those reported to the National Healthcare Safety Network (NHSN). Antibiotic orders were determined to be associated with a SARS-CoV-2 infection if 3 days before or ≤7 days after diagnosis. We characterized the proportion of residents with a SARS-CoV-2 infection with an associated antibiotic by month.We included 2,086 (43%) NHs that had ≤20% difference in total number of SARS-CoV-2 infections documented in PCC and reported to NHSN. From April 2020-November 2021, a total of 118,180 residents with a SARS-CoV-2 infection were identified and 24% had an associated antibiotic prescription (N=27,972). The highest prescription rate (30%, 95% Confidence Interval [29%-31%]) was observed in April 2020 and varied by less than 8% from May 2020-November 2021 (Fig.1). The most commonly prescribed antibiotics were azithromycin (53%), doxycycline (13%) and ceftriaxone (10%). An antibiotic prescription was linked to up to a quarter of NH residents with SARS-CoV-2 infection, highlighting potential opportunities for avoiding unnecessary antibiotic prescribing for viral infections in NHs. Appropriate antibiotic prescribing in NH populations is important to reduce potential harm when antibiotics offer no treatment benefit to the resident. Identifying facility-level characteristics that lead to variability in antibiotic prescribing is a next step to inform antibiotic stewardship interventions.All Authors: No reported disclosures.

Since April 2024, sporadic infections with highly pathogenic avian influenza (HPAI) A(H5) viruses have been detected among dairy farm workers in the United States. To date, infections have mostly been detected through worker monitoring, and have been mild despite the possibility of more severe illness. During June-August 2024, CDC collaborated with the Michigan Department of Health and Human Services and the Colorado Department of Public Health and Environment to implement cross-sectional serologic surveys to ascertain the prevalence of recent infection with HPAI A(H5) virus among dairy workers. In both states, a convenience sample of persons who work in dairies was interviewed, and blood specimens were collected. Among 115 persons, eight (7%; 95% CI = 3.6%-13.1%) had serologic evidence of recent infection with A(H5) virus; all reported milking cows or cleaning the milking parlor. Among persons with serologic evidence of infection, four recalled being ill around the time cows were ill; symptoms began before or within a few days of A(H5) virus detections among cows. This finding supports the need to identify and implement strategies to prevent transmission among dairy cattle to reduce worker exposures and for education and outreach to dairy workers concerning prevention, symptoms, and where to seek medical care if the workers develop symptoms. Timely identification of infected herds can support rapid initiation of monitoring, testing, and treatment for human illness, including mild illness, among exposed dairy workers.

Papua New Guinea lacks data characterising the sexual health needs of younger key populations (KP): female sex workers (FSW) and commercially and sexually exploited girls (CSE), men who have sex with men (MSM), and transgender women (TGW). Biobehavioural surveys among KP were conducted in three cities. We conducted unweighted and weighted analysis for sample and population proportions, respectively. Variables associated with younger versus older age (15-24 versus ≥25 years) were included in the multivariable analysis. Younger FSW/CSEG had greater odds of having both Neisseria gonorrhoea and Chlamydia trachomatis (aOR:3.2, 95%CI 2.0-5.0), or having either infection (aOR:2.2, 95%CI 1.2-4.1) than older peers. They also had lower odds of having tested for HIV (aOR: 0.6, 95%CI 0.4-0.8). Younger MSM/TGW had greater odds of paying for sex in the <6 months (aOR:2.2, 95%CI: 1.5-3.1) and of having been paid for sex (aOR:1.6, 95%CI 1.1-2.4) than their older peers (≥25 years). Younger MSM/TGW had lower odds of having contact with a peer educator ≤12 months (aOR:0.6, 95%CI 0.4-0.9) and having tested for HIV (aOR:0.6, 95%CI: 0.4-0.9). All key populations have substantial sexual health needs, but those of younger members are greatest. Younger key populations would likely benefit from health services designed specifically for them.

BACKGROUND: Borealpox virus (BRPV, formerly known as Alaskapox virus) is a zoonotic member of the Orthopoxvirus genus first identified in a person in 2015. In the six patients with infection previously observed BRPV involved mild, self-limiting illness. We report the first fatal BRPV infection in an immunosuppressed patient. METHODS: A man aged 69 years from Alaska's Kenai Peninsula was receiving anti-CD20 therapy for chronic lymphocytic leukemia. He presented to care for a tender, red papule in his right axilla with increasing induration and pain. The patient failed to respond to multiple prescribed antibiotic regimens and was hospitalized 65 days postsymptom onset for progression of presumed infectious cellulitis. BRPV was eventually detected through orthopoxvirus real-time polymerase chain reaction testing of mucosal swabs. He received combination antiviral therapy, including 21 days of intravenous tecovirimat, intravenous vaccinia immunoglobulin, and oral brincidofovir. Serial serology was conducted on specimens obtained posttreatment initiation. FINDINGS: The patient's condition initially improved with plaque recession, reduced erythema, and epithelization around the axillary lesion beginning one-week post-therapy. He later exhibited delayed wound healing, malnutrition, acute renal failure, and respiratory failure. He died 138 days postsymptom onset. Serologic testing revealed no evidence the patient generated a humoral immune response. No secondary cases were detected. CONCLUSION: This report demonstrates that BRPV can cause overwhelming disseminated infection in certain immunocompromised patients. Based on the patient's initial response, early BRPV identification and antiviral therapies might have been beneficial. These therapies, in combination with optimized immune function, should be considered for patients at risk for manifestations of BRPV.

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

BACKGROUND: Long COVID can lead to functional disabilities and decreased well-being and limit the ability to work. No study has yet assessed associations of SARS-CoV-2-infection and Long COVID with specific measures of well-being and functional disabilities among workers by employment status. METHODS: Using data from the U.S. Behavioral Risk Factor Surveillance System, we assessed the prevalence of functional disabilities and well-being measures among adults of prime working age (25-54 years) by employment status and self-reported COVID-19 and Long COVID history. Within each employment status, we generated adjusted prevalence ratios (aPRs) comparing respondents from each 2022 COVID-19/Long COVID category to respondents in that employment status before the pandemic (2019). RESULTS: In 2022, prevalences of each functional disability except vision and all adverse well-being measures were highest among the 9.2% of respondents reporting a history of Long COVID. For each outcome, prevalences were lowest for workers and highest among those unable to work. 2022 prevalence of cognitive disability (16.4% of employees, 21.4% of the self-employed) and depression (31.2% and 36.4%, respectively) among workers reporting a history of Long COVID were more than double 2019 levels. Increases in cognitive disability and depression were lower but statistically significant among workers not reporting a history of Long COVID. CONCLUSIONS: The high prevalence of functional disabilities and adverse well-being among workers reporting a history of Long COVID have implications for workers and employers. Also concerning are smaller increases among workers not reporting a history of Long COVID, given the large number of affected workers. Mitigating the effects of Long COVID on workers will involve efforts in multiple domains: reducing incidence, increasing healthcare practitioner awareness, improving diagnosis and treatments, and increasing employer awareness of best practices for accommodating workers with Long COVID.

National public health emergency operations centers (PHEOCs) serve as hubs for coordinating information and resources for effective emergency management. In the International Health Regulations (IHR 2005) Monitoring and Evaluation Framework, a simulation exercise is 1 of 4 components that can be used to test the functionality of a country's emergency response capabilities in a simulated situation. To test the functionality of PHEOCs in World Health Organization African Region member states, a regional functional exercise simulating an Ebola virus disease outbreak was conducted. The public health actions taken in response to the simulated outbreak were evaluated against the exercise objectives. Thematic analysis was conducted to summarize key strengths and areas for improvement. From December 6 to 7, 2022, more than 1,000 representatives from 36 of the 47 African Region member states participated in the exercise from their respective PHEOCs. Approximately 95% of the 461 participants polled agreed with the positive responses to the postexercise survey. More than half of the PHEOC participants were able to test their existing emergency preparedness and response plans and became familiar with the expected roles to be fulfilled during an event. Of the participants who responded to the survey, over 90% reported that the exercise helped them understand their roles during emergency management. The exercise met its objectives and provided an opportunity to test the functionality of PHEOCs using realistic scenarios, and it helped participants understand existing response systems and procedures. However, the exercise also revealed areas for improvement in terms of the timing and preparation of participants. We recommend conducting functional exercises at the regional and national levels at least once a year, early or midyear, to allow many stakeholders to take part in the exercise. Moreover, there is a need to train country-level evaluators and controllers in designing and conducting functional exercises.

BACKGROUND: Clusters of invasive group A streptococcal (iGAS) infection, linked to genomically closely related group A streptococcal (GAS) isolates (referred to as genomic clusters), pose public health threats, and are increasingly identified through whole-genome sequencing (WGS) analysis. In this study, we aimed to assess the risk of genomic cluster formation among iGAS cases not already part of existing genomic clusters. METHODS: In this WGS and population-based surveillance study, we analysed iGAS case isolates from the Active Bacterial Core surveillance (ABCs), which is part of the US Centers for Disease Control and Prevention's Emerging Infections Program, in ten US states from Jan 1, 2015, to Dec 31, 2019. We included all residents in ABCs sites with iGAS infections meeting the case definition and excluded non-conforming GAS infections and cases with whole-genome assemblies of the isolate containing fewer than 1·5 million total bases or more than 150 contigs. For iGAS cases we collected basic demographics, underlying conditions, and risk factors for infection from medical records, and for isolates we included emm types, antimicrobial resistance, and presence of virulence-related genes. Two iGAS cases were defined as genomically clustered if their isolates differed by three or less single-nucleotide variants. An iGAS case not clustered with any previous cases at the time of detection, with a minimum trace-back time of 1 year, was defined as being at risk of cluster formation. We monitored each iGAS case at risk for a minimum of 1 year to identify any cluster formation event, defined as the detection of a subsequent iGAS case clustered with the case at risk. We used the Kaplan-Meier method to estimate the cumulative incidence of cluster formation events over time. We used Cox regression to assess associations between features of cases at risk upon detection and subsequent cluster formation. We developed a random survival forest machine-learning model based on a derivation cohort (random selection of 50% of cases at risk) to predict cluster formation risk. This model was validated using a validation cohort consisting of the remaining 50% of cases at risk. FINDINGS: We identified 2764 iGAS cases at risk from 2016 to 2018, of which 656 (24%) formed genomic clusters by the end of 2019. Overall, the cumulative incidence of cluster formation was 0·057 (95% CI 0·048-0·066) at 30 days after detection, 0·12 (0·11-0·13) at 90 days after detection, and 0·16 (0·15-0·18) at 180 days after detection. A higher risk of cluster formation was associated with emm type (adjusted hazard ratio as compared with emm89 was 2·37 [95% CI 1·71-3·30] for emm1, 2·72 [1·82-4·06] for emm3, 2·28 [1·49-3·51] for emm6, 1·47 [1·05-2·06] for emm12, and 2·21 [1·38-3·56] for emm92), homelessness (1·42 [1·01-1·99]), injection drug use (2·08 [1·59-2·72]), residence in a long-term care facility (1·78 [1·29-2·45]), and the autumn-winter season (1·34 [1·14-1·57]) in multivariable Cox regression analysis. The machine-learning model stratified the validation cohort (n=1382) into groups at low (n=370), moderate (n=738), and high (n=274) risk. The 90-day risk of cluster formation was 0·03 (95% CI 0·01-0·05) for the group at low risk, 0·10 (0·08-0·13) for the group at moderate risk, and 0·21 (0·17-0·25) for the group at high risk. These results were consistent with the cross-validation outcomes in the derivation cohort. INTERPRETATION: Using population-based surveillance data, we found that pathogen, host, and environment factors of iGAS cases were associated with increased likelihood of subsequent genomic cluster formation. Groups at high risk were consistently identified by a predictive model which could inform prevention strategies, although future work to refine the model, incorporating other potential risk factors such as host contact patterns and immunity to GAS, is needed to improve its predictive performance. FUNDING: Centers for Disease Control and Prevention.

BACKGROUND: SMS text messaging- and internet-based self-reporting systems can supplement existing vaccine safety surveillance systems, but real-world participation patterns have not been assessed at scale. OBJECTIVE: This study aimed to describe the participation rates of a new SMS text messaging- and internet-based self-reporting system called the Kaiser Permanente Side Effect Monitor (KPSEM) within a large integrated health care system. METHODS: We conducted a prospective cohort study of Kaiser Permanente Southern California (KPSC) patients receiving a COVID-19 vaccination from April 23, 2021, to July 31, 2023. Patients received invitations through flyers, SMS text messages, emails, or patient health care portals. After consenting, patients received regular surveys to assess adverse events up to 5 weeks after each dose. Linkage with medical records provided demographic and clinical data. In this study, we describe KPSEM participation rates, defined as providing consent and completing at least 1 survey within 35 days of COVID-19 vaccination. RESULTS: Approximately, 8% (164,636/2,091,975) of all vaccinated patients provided consent and completed at least 1 survey within 35 days. The lowest participation rates were observed for parents of children aged 12-17 years (1349/152,928, 0.9% participation rate), and the highest participation was observed among older adults aged 61-70 years (39,844/329,487, 12.1%). Persons of non-Hispanic White race were more likely to participate compared with other races and ethnicities (13.1% vs 3.9%-7.5%, respectively; P<.001). In addition, patients residing in areas with a higher neighborhood deprivation index were less likely to participate (5.1%, 16,503/323,122 vs 10.8%, 38,084/352,939 in the highest vs lowest deprivation quintiles, respectively; P<.001). Invitations through the individual's Kaiser Permanente health care portal account and by SMS text message were associated with the highest participation rate (19.2%, 70,248/366,377 and 10.5%, 96,169/914,793, respectively), followed by email (19,464/396,912, 4.9%) and then QR codes on flyers (25,882/2,091,975, 1.2%). SMS text messaging-based surveys demonstrated the highest sustained daily response rates compared with internet-based surveys. CONCLUSIONS: This real-world prospective study demonstrated that a novel digital vaccine safety self-reporting system implemented through an integrated health care system can achieve high participation rates. Linkage with participants' electronic health records is another unique benefit of this surveillance system. We also identified lower participation among selected vulnerable populations, which may have implications when interpreting data collected from similar digital systems.

BACKGROUND: Workers in healthcare and other essential occupations had elevated risks for COVID-19 infection early in the pandemic. No survey of U.S. workers to date has comprehensively assessed the prevalence of both COVID-19 and Long COVID across industries and occupations (I&O) at a detailed level. METHODS: Behavioral Risk Factor Surveillance System data for 2022 from 39 states, Guam, and the U.S. Virgin Islands were used to estimate prevalence of self-reported history of COVID-19 and Long COVID, as well as the prevalence of Long COVID among those reporting prior COVID-19, by broad and detailed I&O. Adjusted prevalence ratios were used to compare outcome prevalence in each I&O to prevalence among all other workers combined. RESULTS: By broad I&O, workers in healthcare, protective services, and education had elevated prevalences of COVID-19. The prevalence of Long COVID was elevated in healthcare and protective service but not education workers. Detailed I&O with significantly elevated prevalences of COVID-19 but not Long COVID included Dairy Product Manufacturing industry workers and subsets of mining workers. Both COVID-19 and Long COVID were elevated among bartenders/drinking places and personal care and appearance workers. The prevalence of Long COVID was elevated among farmworkers who reported having had COVID-19. CONCLUSIONS: Industries and occupations with elevated levels of COVID-19 or Long COVID in this study may warrant increased measures to prevent transmission of airborne respiratory viruses. Accommodations are a key component for supporting workers in all workplaces. This new information about the distribution of Long COVID by I&O suggests where employer understanding and implementation of tailored workplace supports and accommodations are most needed to support continued employment of affected workers.

INTRODUCTION: An error grid compares measured versus reference glucose concentrations to assign clinical risk values to observed errors. Widely used error grids for blood glucose monitors (BGMs) have limited value because they do not also reflect clinical accuracy of continuous glucose monitors (CGMs). METHODS: Diabetes Technology Society (DTS) convened 89 international experts in glucose monitoring to (1) smooth the borders of the Surveillance Error Grid (SEG) zones and create a user-friendly tool-the DTS Error Grid; (2) define five risk zones of clinical point accuracy (A-E) to be identical for BGMs and CGMs; (3) determine a relationship between DTS Error Grid percent in Zone A and mean absolute relative difference (MARD) from analyzing 22 BGM and nine CGM accuracy studies; and (4) create trend risk categories (1-5) for CGM trend accuracy. RESULTS: The DTS Error Grid for point accuracy contains five risk zones (A-E) with straight-line borders that can be applied to both BGM and CGM accuracy data. In a data set combining point accuracy data from 18 BGMs, 2.6% of total data pairs equally moved from Zones A to B and vice versa (SEG compared with DTS Error Grid). For every 1% increase in percent data in Zone A, the MARD decreased by approximately 0.33%. We also created a DTS Trend Accuracy Matrix with five trend risk categories (1-5) for CGM-reported trend indicators compared with reference trends calculated from reference glucose. CONCLUSION: The DTS Error Grid combines contemporary clinician input regarding clinical point accuracy for BGMs and CGMs. The DTS Trend Accuracy Matrix assesses accuracy of CGM trend indicators.

While the health of all depends on the food chain, few studies have focused systematically on the health of food chain workers themselves (production, manufacturing, wholesale, retail, and commercial and institutional services). In this study we used 2018 and 2019 data from the Behavioral Risk Factor Surveillance System (BRFSS) to examine health-related metrics of food chain workers, combined and by industry sector, compared to non-food chain workers, among 32 U.S. states. Logistic regression indicated U.S. food chain workers had higher prevalences of barriers to health care access, smoking, no physical exercise, and poor self-reported health than all other workers. Patterns were similar among food chain workers in all industry sectors except wholesale. Additionally, commercial food services workers had higher prevalence of poor mental health, while institutional food services workers had higher prevalences of obesity, diabetes, and hypertension than all other workers. We discuss implications of these results for interventions, with specific attention to improving employment conditions. Food chain worker health is critical for food system sustainability and population health equity.

Respiratory syncytial virus (RSV) is the second most common pathogen causing infant mortality. Additionally, RSV is a major cause of morbidity and mortality in older adults (age ≥60 years) similar to influenza. A protein-based maternal vaccine and monoclonal antibody (mAb) are now market-approved to protect infants, while an mRNA and two protein-based vaccines are approved for older adults. First-year experience protecting infants with nirsevimab in high-income countries shows a major public health benefit. It is expected that the RSV vaccine landscape will continue to develop in the coming years to protect all people globally. The vaccine and mAb landscape remain active with 30 candidates in clinical development using four approaches: protein-based, live-attenuated and chimeric vector, mRNA, and mAbs. Candidates in late-phase trials aim to protect young infants using mAbs, older infants and toddlers with live-attenuated vaccines, and children and adults using protein-based and mRNA vaccines. This Review provides an overview of RSV vaccines highlighting different target populations, antigens, and trial results. As RSV vaccines have not yet reached low-income and middle-income countries, we outline urgent next steps to minimise the vaccine delay.

Invasive pneumococcal disease (IPD) due to non-vaccine serotypes after the introduction of pneumococcal conjugate vaccines (PCV) remains a global concern. This study used pathogen genomics to evaluate changes in invasive pneumococcal lineages before, during and after vaccine introduction in South Africa. We included genomes (N = 3104) of IPD isolates from individuals aged <18 years (2005-20), spanning four periods: pre-PCV, PCV7, early-PCV13, and late-PCV13. Significant incidence reductions occurred among vaccine-type lineages in the late-PCV13 period compared to the pre-PCV period. However, some vaccine-type lineages continued to cause invasive disease and showed increasing effective population size trends in the post-PCV era. A significant increase in lineage diversity was observed from the PCV7 period to the early-PCV13 period (Simpson's diversity index: 0.954, 95% confidence interval 0.948-0.961 vs 0.965, 0.962-0.969) supporting intervention-driven population structure perturbation. Increases in the prevalence of penicillin, erythromycin, and multidrug resistance were observed among non-vaccine serotypes in the late-PCV13 period compared to the pre-PCV period. In this work we highlight the importance of continued genomic surveillance to monitor disease-causing lineages post vaccination to support policy-making and future vaccine designs and considerations.

OBJECTIVES: Public health emergencies can elevate the risk for intimate partner violence (IPV). Our objectives were 2-fold: first, to assess the prevalence of physical IPV and increased aggression from a husband or partner that occurred during pregnancy and was perceived to be due to the COVID-19 pandemic; second, to examine associations between these experiences and (1) COVID-19-related stressors and (2) postpartum outcomes. METHODS: We used data from the Pregnancy Risk Assessment Monitoring System that were collected in 29 US jurisdictions among individuals with a live birth in 2020. We estimated the prevalence of violence during pregnancy by demographic characteristics and COVID-19-related stressors. We calculated adjusted prevalence ratios (APRs) to examine associations of physical IPV or increased aggression with COVID-19-related stressors, postpartum outcomes, and infant birth outcomes. RESULTS: Among 14 154 respondents, 1.6% reported physical IPV during pregnancy, and 3.1% reported increased aggression by a husband or partner due to the COVID-19 pandemic. Respondents experiencing any economic, housing, or childcare COVID-19-related stressors reported approximately twice the prevalence of both types of violence as compared with those without COVID-19-related stressors. Physical IPV and increased aggression were associated with a higher prevalence of postpartum depressive symptoms (APRs, 1.73 and 2.28, respectively) and postpartum cigarette smoking (APRs, 1.74 and 2.19). Physical IPV was associated with a lower prevalence of attending postpartum care visits (APR, 1.84). CONCLUSIONS: Our findings support the need for ongoing efforts to prevent IPV during pregnancy and to ensure the availability of resources during public health emergencies.

OBJECTIVES: To estimate the impact of occupational injury and illness on opioid-related mortality while accounting for confounding by preinjury opioid use. METHODS: We employed a retrospective cohort study design using Washington State workers' compensation data for 1994-2000 injuries linked to US Social Security Administration earnings and mortality data and National Death Index (NDI) cause of death data from 1994 to 2018. We categorised injuries as lost-time versus medical-only, where the former involved more than 3 days off work or permanent disability. We determined death status and cause of death from NDI records. We modelled separate Fine and Gray subdistribution hazard ratios (sHRs) and 95% CIs for injured men and women for opioid-related and all drug-related mortality through 2018. We used quantitative bias analysis to account for unmeasured confounding by preinjury opioid use. RESULTS: The hazard of opioid-related mortality was elevated for workers with lost-time relative to medical-only injuries: sHR for men: 1.53, 95% CI 1.41 to 1.66; for women: 1.31, 95% CI 1.16 to 1.48. Accounting for preinjury opioid use, effect sizes were reduced but remained elevated: sHR for men was 1.43, 95% simulation interval (SI) 1.20 to 1.69; for women: 1.27, 95% SI 1.10 to 1.45. CONCLUSIONS: Occupational injuries and illnesses severe enough to require more than 3 days off work are associated with an increase in the hazard of opioid-related mortality. The estimated increase is reduced when we account for preinjury opioid use, but it remains substantial. Reducing work-related injuries and postinjury opioid prescribing and improving employment and income security may decrease opioid-related mortality.

BACKGROUND: The Centers for Disease Control and Prevention's Active Bacterial Core surveillance (ABCs) identified increased serotype 4 invasive pneumococcal disease (IPD), particularly among adults experiencing homelessness (AEH). METHODS: We quantified IPD cases during 2016-2022. Employing genomic-based characterization of IPD isolates, we identified serotype-switch variants. Recombinational analyses were used to identify the genetic donor and recipient strains that generated a serotype 4 progeny strain. We performed phylogenetic analyses of the serotype 4 progeny and serotype 12F genetic recipient to determine genetic distances. RESULTS: We identified 30 inter-related (0-21 nucleotide differences) IPD isolates recovered during 2022-2023, corresponding to a serotype 4 capsular-switch variant. This strain arose through a multi-fragment recombination event between serotype 4/ST10172 and serotype 12F/ST220 parental strains. Twenty-five of the 30 cases occurred within Oregon. Of 29 cases with known residence status, 16 occurred in AEH. Variant emergence coincided with a 2.6-fold increase (57 to 148) of cases caused by the serotype 4/ST10172 donor lineage in 2022 compared to 2019 and its first appearance in Oregon. Most serotypes showed sequential increases of AEH IPD/all IPD ratios during 2016-2022 (for all serotypes combined, 247/2198, 11.2% during 2022 compared to 405/5317, 7.6% for 2018-2019, p<0.001). Serotypes 4 and 12F each caused more IPD than any other serotypes in AEH during 2020-2022 (207 combined reported cases primarily in 4 western states accounting for 38% of IPD in AEH). CONCLUSION: Expansion and increased transmission of serotypes 4 and 12F among adults potentially led to recent genesis of an impactful hybrid "serotype-switch" variant.

BACKGROUND: Although guidelines recommend risk assessment for hospital-acquired venous thromboembolism (HA-VTE) to inform prophylaxis decisions, studies demonstrate inappropriate utilization of pharmacoprophylaxis in hospitalized medical patients. Predictors of pharmacoprophylaxis initiation in medical inpatients remain largely unknown. OBJECTIVE: To determine factors associated with HA-VTE pharmacoprophylaxis initiation in adults hospitalized on medical services. DESIGN: Cohort study using electronic health record data from adult patients hospitalized on medical services at four academic medical centers between 2016 and 2019. PARTICIPANTS: Among 111,550 admissions not on intermediate or full-dose anticoagulation, 48,520 (43.5%) received HA-VTE pharmacoprophylaxis on the day of or the day after admission. MAIN MEASURES: Candidate predictors of HA-VTE pharmacoprophylaxis initiation, including known HA-VTE risk factors, predicted HA-VTE risk, and bleeding diagnoses present on admission. KEY RESULTS: After adjustment for age, sex, race/ethnicity, and study site, the strongest clinical predictors of HA-VTE pharmacoprophylaxis initiation were malnutrition and chronic obstructive pulmonary disease. Thrombocytopenia and history of gastrointestinal bleeding were associated with decreased odds of HA-VTE pharmacoprophylaxis initiation. Patients in the highest two tertiles of predicted HA-VTE risk were less likely to receive HA-VTE pharmacoprophylaxis than patients in the lowest (1(st)) tertile (OR 0.84, 95% CI [0.81, 0.86] for 2(nd) tertile, OR 0.95, 95% CI [0.92, 0.98] for 3(rd) tertile). CONCLUSIONS: Among patients not already receiving anticoagulants, HA-VTE pharmacoprophylaxis initiation during the first two hospital days was lower in patients with higher predicted HA-VTE risk and those with risk factors for bleeding. Reasons for not initiating pharmacoprophylaxis in those with higher predicted risk could not be assessed.

IMPORTANCE: Despite significant progress made toward tuberculosis (TB) elimination, racial and ethnic disparities persist in TB incidence and case-fatality rates in the US. OBJECTIVE: To estimate the health outcomes and economic cost of TB disparities among US-born persons from 2023 to 2035. DESIGN, SETTING, AND PARTICIPANTS: Generalized additive regression models projecting trends in TB incidence and case-fatality rates from 2023 to 2035 were fit based on national TB surveillance data for 2010 to 2019 in the 50 US states and the District of Columbia among US-born persons. This baseline scenario was compared with alternative scenarios in which racial and ethnic disparities in age- and sex-adjusted incidence and case-fatality rates were eliminated by setting rates for each race and ethnicity to goal values. Additional scenarios were created examining the potential outcomes of delayed reduction of racial and ethnic disparities. The potential benefits of eliminating disparities from differences between baseline and alternative scenario outcomes were quantified. Data were analyzed from January 2010 to December 2019. EXPOSURES: Non-Hispanic American Indian or Alaska Native, non-Hispanic Asian, non-Hispanic Black, Hispanic, non-Hispanic Native Hawaiian or Other Pacific Islander, or non-Hispanic White race and ethnicity. MAIN OUTCOMES AND MEASURES: TB cases and deaths averted, quality-adjusted life years gained, and associated costs from a societal perspective. RESULTS: The study included 31 811 persons with reported TB from 2010 to 2019 (mean [SD] age, 47 [24] years; 20 504 [64%] male; 1179 [4%] American Indian or Alaska Native persons; 1332 [4%] Asian persons; 12 152 [38%] Black persons; 6595 [21%] Hispanic persons; 299 [1%] Native Hawaiian or Other Pacific Islander persons; and 10 254 [32%] White persons). There were 3722 persons with a reported TB death. Persistent racial and ethnic disparities were associated with an estimated 11 901 of 26 203 TB cases among US-born persons (45%; 95% uncertainty interval [UI], 44%-47%), 1421 of 3264 TB deaths among US-born persons (44%; 95% UI, 39%-48%), and an economic cost of $914 (95% UI, $675-$1147) million from 2023 to 2035. Delayed goal attainment reduced the estimated avertable TB outcomes by 505 (95% UI, 495-518) TB cases, 55 (95% UI, 51-59) TB deaths, and $32 (95% UI, $24-$40) million in societal costs annually. CONCLUSIONS AND RELEVANCE: In this modeling study of racial and ethnic disparities of TB, these disparities were associated with substantial future health and economic outcomes of TB among US-born persons without interventions beyond current efforts. Actions to eliminate disparities may reduce the excess TB burden among these persons and may contribute to accelerating TB elimination within the US.

Measles is a highly contagious disease and remains a major cause of child mortality worldwide. While measles vaccine is highly effective, high levels of population immunity are needed to prevent outbreaks. Simple but accurate tools are needed to estimate the profile of population measles immunity by age to identify and fill immunity gaps caused by low levels of vaccination coverage. The measles immunity profile estimates and visualizes the percentage of each birth cohort immune or susceptible to measles based on measles vaccination coverage. Several tools that employed this approach have been developed in the past, including informal unpublished versions. However, these tools used varying assumptions and produced inconsistent results. We updated the measles population immunity profile methodology to standardize and better document the assumptions and methods; provide timely estimates of measles population immunity; and facilitate prompt actions to close immunity gaps and prevent outbreaks. We recommend assuming that the second dose of the measles-containing vaccine (MCV2) and doses given during supplementary immunization activities (SIAs) first reach children who have been previously vaccinated against measles, so that previously unvaccinated children are reached only when the coverage of MCV2 or SIA is higher than the coverage achieved by all previous measles vaccination opportunities. This updated method provides a conservative estimate of immunization program impact to assess measles outbreak risk and to facilitate early planning of timely preventive SIAs to close population immunity gaps.

Background: The first licensed malaria vaccine, RTS,S/AS01<inf>E</inf>, confers moderate protection against symptomatic disease. Because many malaria infections are asymptomatic, we conducted a large-scale longitudinal parasite genotyping study of samples from a clinical trial exploring how vaccine dosing regimen affects vaccine efficacy. Method(s): Between Sept 28, 2017, and Sept 25, 2018, 1500 children aged 5-17 months were randomly assigned (1:1:1:1:1) to receive four different RTS,S/AS01<inf>E</inf> regimens or a rabies control vaccine in a phase 2b open-label clinical trial in Ghana and Kenya. Participants in the four RTS,S groups received two full doses at month 0 and month 1 and either full doses at month 2 and month 20 (group R012-20); full doses at month 2, month 14, month 26, and month 38 (group R012-14); fractional doses at month 2, month 14, month 26, and month 38 (group Fx012-14; early fourth dose); or fractional doses at month 7, month 20, and month 32 (group Fx017-20; delayed third dose). We evaluated the time to the first new genotypically detected infection and the total number of new infections during two follow-up periods (12 months and 20 months) in more than 36 000 dried blood spot specimens from 1500 participants. To study vaccine effects on time to the first new infection, we defined vaccine efficacy as one minus the hazard ratio (HR; RTS,S vs control) of the first new infection. We performed a post-hoc analysis of vaccine efficacy based on malaria infection status at first vaccination and force of infection by month 2. This trial (MAL-095) is registered with ClinicalTrials.gov, NCT03281291. Finding(s): We observed significant and similar vaccine efficacy (25-43%; 95% CI union 9-53) against first new infection for all four RTS,S/AS01<inf>E</inf> regimens across both follow-up periods (12 months and 20 months). Each RTS,S/AS01<inf>E</inf> regimen significantly reduced the mean number of new infections in the 20-month follow-up period by 1.1-1.6 infections (95% CI union 0.6-2.1). Vaccine efficacy against first new infection was significantly higher in participants who were infected with malaria (68%; 95% CI 50-80) than in those who were uninfected (37%; 23-48) at the first vaccination (p=0.0053). Interpretation(s): All tested dosing regimens blocked some infections to a similar degree. Improved vaccine efficacy in participants infected during vaccination could suggest new strategies for highly efficacious malaria vaccine development and implementation. Funding(s): GlaxoSmithKline Biologicals SA, PATH, Bill & Melinda Gates Foundation, and the German Federal Ministry of Education and Research. Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Many individually randomized group treatment (IRGT) trials randomly assign individuals to study arms but deliver treatments via shared agents, such as therapists, surgeons, or trainers. Post-randomization interactions induce correlations in outcome measures between participants sharing the same agent. Agents can be nested in or crossed with trial arm, and participants may interact with a single agent or with multiple agents. These complications have led to ambiguity in choice of models but there have been no systematic efforts to identify appropriate analytic models for these study designs. To address this gap, we undertook a simulation study to examine the performance of candidate analytic models in the presence of complex clustering arising from multiple membership, single membership, and single agent settings, in both nested and crossed designs and for a continuous outcome. With nested designs, substantial type I error rate inflation was observed when analytic models did not account for multiple membership and when analytic model weights characterizing the association with multiple agents did not match the data generating mechanism. Conversely, analytic models for crossed designs generally maintained nominal type I error rates unless there was notable imbalance in the number of participants that interact with each agent.

OBJECTIVES: . The United States Centers for Disease Control and Prevention (CDC) conducts active surveillance for typhoid fever cases caused by Salmonella enterica serovar Typhi (Typhi). Here we describe the characteristics of the first two cases of mph(A)-positive azithromycin-resistant Typhi identified through US surveillance. METHODS: . Isolates were submitted to public health laboratories, sequenced, and screened for antimicrobial resistance determinants and plasmids, as part of CDC PulseNet's routine genomic surveillance. Antimicrobial susceptibility testing and long-read sequencing were also performed. Basic case information (age, sex, travel, outcome) was collected through routine questionnaires; additional epidemiological data was requested through follow-up patient interviews. RESULTS: . The patients are related and both reported travel to India (overlapping travel dates) before illness onset. Both Typhi genomes belong to the GenoTyphi lineage 4.3.1.1 and carry the azithromycin-resistance gene mph(A) on a PTU-FE (IncFIA/FIB/FII) plasmid. These strains differ genetically from mph(A)-positive Typhi genomes recently reported from Pakistan, suggesting independent emergence of azithromycin resistance in India. CONCLUSIONS: . Cases of typhoid fever caused by Typhi strains resistant to all available oral treatment options are cause for concern and support the need for vaccination of travelers to Typhi endemic regions. US genomic surveillance serves as an important global sentinel for detection of strains with known and emerging antimicrobial resistance profiles, including strains from areas where routine surveillance is not conducted.

BACKGROUND: Antiviral post-exposure prophylaxis with neuraminidase inhibitors can reduce the incidence of influenza and the risk of symptomatic influenza, but the efficacy of the other classes of antiviral remains unclear. To support an update of WHO influenza guidelines, this systematic review and network meta-analysis evaluated antiviral drugs for post-exposure prophylaxis of 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 evaluated the efficacy and safety of antivirals compared with another antiviral or placebo or standard care for prevention of influenza. Pairs of reviewers independently screened studies, extracted data, and assessed the risk of bias. We performed network meta-analyses with frequentist random effects model and assessed the certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. The outcomes of interest were symptomatic or asymptomatic infection, admission to hospital, all-cause mortality, adverse events related to antivirals, and serious adverse events. This study is registered with PROSPERO, CRD42023466450. FINDINGS: Of 11 845 records identified by our search, 33 trials of six antivirals (zanamivir, oseltamivir, laninamivir, baloxavir, amantadine, and rimantadine) that enrolled 19 096 individuals (mean age 6·75-81·15 years) were included in this systematic review and network meta-analysis. Most of the studies were rated as having a low risk of bias. Zanamivir, oseltamivir, laninamivir, and baloxavir probably achieve important reductions in symptomatic influenza in individuals at high risk of severe disease (zanamivir: risk ratio 0·35, 95% CI 0·25-0·50; oseltamivir: 0·40, 0·26-0·62; laninamivir: 0·43, 0·30-0·63; baloxavir: 0·43, 0·23-0·79; moderate certainty) when given promptly (eg, within 48 h) after exposure to seasonal influenza. These antivirals probably do not achieve important reductions in symptomatic influenza in individuals at low risk of severe disease when given promptly after exposure to seasonal influenza (moderate certainty). Zanamivir, oseltamivir, laninamivir, and baloxavir might achieve important reductions in symptomatic zoonotic influenza in individuals exposed to novel influenza A viruses associated with severe disease in infected humans when given promptly after exposure (low certainty). Oseltamivir, laninamivir, baloxavir, and amantadine probably decrease the risk of all influenza (symptomatic and asymptomatic infection; moderate certainty). Zanamivir, oseltamivir, laninamivir, and baloxavir probably have little or no effect on prevention of asymptomatic influenza virus infection or all-cause mortality (high or moderate certainty). Oseltamivir probably has little or no effect on admission to hospital (moderate certainty). All six antivirals do not significantly increase the incidence of drug-related adverse events or serious adverse events, although the certainty of evidence varies. INTERPRETATION: Post-exposure prophylaxis with zanamivir, oseltamivir, laninamivir, or baloxavir probably decreases the risk of symptomatic seasonal influenza in individuals at high risk for severe disease after exposure to seasonal influenza viruses. Post-exposure prophylaxis with zanamivir, oseltamivir, laninamivir, or baloxavir might reduce the risk of symptomatic zoonotic influenza after exposure to novel influenza A viruses associated with severe disease in infected humans. FUNDING: World Health Organization.