OBJECTIVES: To evaluate the effect of high-dose isoniazid in patients with isoniazid-resistant TB by its bactericidal activity after 1 or more weeks of treatment. SUBJECTS AND METHODS: Using the rapid direct method of phenotypic drug susceptibility testing, we screened persons with positive sputum microscopy results and genotypic drug resistance for isoniazid resistance. Those with no growth at a critical concentration of 2.0 mg/L were invited to participate in a trial of high-dose isoniazid monotherapy lasting 6 days. After 3 days of no treatment, patients received isoniazid 15 mg/kg and were followed with serial quantitative sputum cultures from Days 0 to 6. RESULTS: We enrolled 15 patients after a median of 2 weeks standard first-line treatment. Their median bacillary count on Day 0 was 4.9 log(10) cfu/mL on solid agar, and the time to detection (TTD) was 200 h in liquid medium. Neither metric showed meaningful change in bacillary burden over 6 days, declining by a non-significant 0.08 log(10) cfu/mL/d on solid media and slowing TTD by 23 h. These effects did not differ by degree of isoniazid resistance or specific Inhibin Subunit Alpha (inhA) gene mutations. CONCLUSIONS: The utility of high-dose isoniazid against low-level isoniazid resistance beyond the first 2 weeks of chemotherapy should be reconsidered.

Data-driven approaches to clinical research are necessary for understanding and effectively treating infectious diseases. However, challenges such as issues with data validity, lack of collaboration, and difficult-to-treat infectious diseases (e.g., those that are rare or newly emerging) hinder research. Prioritizing innovative methods to facilitate the continued use of data generated during routine clinical care for research, but in an organized, accelerated, and shared manner, is crucial. This study investigates the potential of CURE ID, an open-source platform to accelerate drug-repurposing research for difficult-to-treat diseases, with COVID-19 as a use case. Data from eight US health systems were analyzed using least absolute shrinkage and selection operator (LASSO) regression to identify key predictors of 28-day all-cause mortality in COVID-19 patients, including demographics, comorbidities, treatments, and laboratory measurements captured during the first two days of hospitalization. Key findings indicate that age, laboratory measures, severity of illness indicators, oxygen support administration, and comorbidities significantly influenced all-cause 28-day mortality, aligning with previous studies. This work underscores the value of collaborative repositories like CURE ID in providing robust datasets for prognostic research and the importance of factor selection in identifying key variables, helping to streamline future research and drug-repurposing efforts.

Background: A contemporary description and estimates for rates of chronic kidney disease (CKD) in type 1 diabetes are needed to inform risk reduction strategies. The study aim was to assess prevalence and severity of CKD based on a population with type 1 diabetes receiving care at a large United States health system. Methods: Type 1 diabetes was identified through the Providence health system electronic health records during 2013–2022. Prevalent CKD was defined cross-sectionally by ≥ 90-day persistence of estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, urine albumin-to-creatinine ratio ≥30 mg/g, or urine protein-to-creatinine ratio ≥0.15 g/g. Multivariable logistic regression models analyzed variable associations with CKD and severe kidney disease (eGFR < 45 mL/min/1.73 m2, dialysis, or transplant). Findings: The study population (N = 23,589) was 48.6% female with a mean ± SD age of 38 ± 17 years. CKD prevalence was 27.1%. Higher odds of CKD were found for females (odds ratio: 1.36 [95% confidence interval]: 1.26–1.47); age 60–79 years (reference 12–17 years; 2.22 [1.83–2.69]); Asian (reference White; 1.71 [1.20–2.44]), Black or African American (1.76 [1.45–2.14]), and Other race (1.33 [1.04–1.71]) populations. CKD odds were higher with hypertension, heart failure, and atherosclerotic cardiovascular disease. Severe kidney disease was present in 10.8% with higher odds among Black or African American (2.08 [1.23–3.54]) and Native Hawaiian or Pacific Islander (2.62 [1.28–5.38]) populations. Interpretation: CKD was present in nearly one of three persons with type 1 diabetes with higher risks for females, older adults, racial and ethnic minorities, and those with cardiovascular diseases. Severe kidney disease was found in over one-tenth and more likely in Black or African American and Native Hawaiian or Pacific Islander populations. Focus on disproportionately affected groups who may benefit from monitoring and interventions to improve clinical outcomes will be important for public health and health system strategies to reduce risks of CKD and severe kidney disease in type 1 diabetes. Funding: This work was supported in part by CDC project numbers 75D301-21-P-12254 and 75D301-23-C-18264, and in part by Brigham Research Institute. © 2025 The Author(s)

INTRODUCTION: Retention in care and antiretroviral therapy (ART) adherence are major clinical and public health challenges in the treatment of HIV in the United States. Traditional data to care (D2C) approaches use health department surveillance data to promote retention in HIV care, with challenges in the timeliness of data and inconclusive findings. Earlier identification of people with HIV who are at risk of loss from care-such as when an ART prescription is not filled-represents a new direction for D2C (D2C-Rx or prescription-based D2C). METHODS: We designed the Antiretroviral Improvement among Medicaid EnrolleeS (AIMS) study, a D2C-Rx initiative in Virginia, which leveraged real-time administrative claims from Virginia Medicaid and HIV surveillance data from Virginia Department of Health (April 2023-June 2024). AIMS was a statewide cluster-randomized, controlled trial comparing a phased, multi-level program of support (intervention) to usual care, among Virginia Medicaid enrollees without current ART prescriptions. Support included a provider-level component for those with no prior ART prescription and patient-level component for those with a > 30-90-day late ART prescription refill(s). We hypothesized that AIMS would increase HIV viral suppression and improve ART adherence at 12 months compared to usual care. We describe the original study protocol and discuss changes implemented to the study design and program implementation. We also consider key methodologic contributions, as well as limitations and challenges to patient- and provider-level enrollment, such as ART prescription data accuracy. ETHICS AND DISSEMINATION: This study was reviewed and approved by the Institutional Review Board of Virginia Commonwealth University (HM20018229). REGISTRATION: The trial is registered at clinicaltrials.gov (NCT05477485).

To understand the potential human health effects of exposure to hazardous substances among first responders from the East Palestine train derailment, an electronic self-administered Assessment of Chemical Exposures (ACE) survey was created and available to first responders between February-March 2023. Among the 339 completed responder surveys analyzed, most reported working at least 1 day during the incident between February 3-8, 2023. Most (79%) reported inhaling, touching, or swallowing potentially harmful substances and did not report using a face mask or respirator while working (75%). Nearly half reported at least 1 new or worsening physical symptom after incident response. These findings support several recommendations to mitigate exposure to hazardous substances among first responders during future incidents, including using a hierarchy of controls framework to reduce exposure to hazards, timely communication of possible hazardous substances involved in the event, and using the Emergency Responder Health Monitoring Surveillance (ERHMS) framework.

BACKGROUND: Rapid linkage to HIV care and antiretroviral therapy (ART) initiation is now the standard of care for treating people with HIV (PWH). Understanding and intervening on barriers to rapid enrollment and ART initiation are needed to meet the goals of the Ending the HIV Epidemic in the U.S. initiative. METHODS: We analyzed 2021 data from the Medical Monitoring Project on characteristics of 455 facilities providing care to a national probability sample of U.S. PWH. RESULTS: Overall, only 19.9% (95% CI 16.0%-23.9%) of HIV facilities could routinely offer a first appointment in <1 business day (rapid enrollment). The most commonly reported barriers to rapid enrollment were insufficient provider capacity (56%), patient preference (50%), and patients lacking required documents (19%). The most commonly reported documents required for enrollment were positive HIV antibody or detectable viral load (52%), government-issued identification (36%), proof of residence (24%), and proof of income (22%). RWHAP-funded facilities more frequently required these documents than non-RWHAP-funded facilities. Most facilities (73%) were routinely able to obtain a 30-day supply of ART during the first HIV care provider visit (rapid ART initiation). The most commonly reported barriers to rapid ART included unavailable test results (56%), delays in getting medication paid for (49%), unavailable starter packs (36%), inability to afford copayment (31%), and patient preference (29%). CONCLUSION: Structural, provider-related, or patient-level barriers may delay rapid clinic enrollment or ART initiation. HIV care programs can benefit from removing barriers to care, easing requirements for clinical enrollment and ART prescriptions, and improving patient readiness.

BACKGROUND: Nursing homes (NHs) were disproportionately affected by the COVID-19 pandemic. However, little is known regarding the kinetics of SARS-CoV-2 shedding in NH residents and staff, which could inform treatment and infection prevention. METHODS: We enrolled NH residents and staff in eight US states from April to November 2023 and analyzed the kinetics of SARS-CoV-2 using serial antigen and molecular (RT-PCR) tests, whole genome sequencing, and viral culture (VC). Symptoms, vaccination, and treatment were collected via interviews and chart review. Viral load trajectories were modeled with gamma distribution functional forms. Antigen and VC test positivity over time were assessed using a Chi-squared test. RESULTS: Of the 587 enrolled participants, 86 tested positive and 73 underwent testing for ≥ 10 days; most residents (78%) and staff (87%) had ≥ 3 COVID-19 vaccine doses. The modeled SARS-CoV-2 proliferation period (period prior to reaching peak viral load) had ended for 48% (14/29) of residents and 56% (9/16) of staff when they took the initial RT-PCR test. Both antigen and VC showed higher positivity rates early in the course of disease (Days 0-5 vs. Days ≥ 6) (antigen: p < 0·001, VC: p < 0·001). VC positivity was 15% after Day 5 (14/96); two participants were VC positive after Day 10. CONCLUSIONS: Peak viral load occurs early in the disease, suggesting asymptomatic and presymptomatic transmission may be a significant driver of transmission. Only two participants had a positive VC after Day 10, supporting current isolation and return to work recommendations.

BACKGROUND: The 2021 update of the CDC clinical guidelines for HIV preexposure prophylaxis (PrEP) recommended both antigen/antibody (Ag/Ab) and RNA testing at PrEP initiation and routine follow-up. We assessed real-world utilization and performance of HIV tests among oral PrEP users. METHODS: An oral PrEP user cohort was constructed using the HealthVerity database that included linked diagnoses, laboratory tests, and prescriptions from December 2018 to August 2023. Data was stratified by guideline pre- (2019-2021) and post-update (2022-2023) periods. For each period, we assessed the agreement between same-day HIV Ag/Ab and RNA results and calculated the false positive rate (FPR) and positive predictive values (PPV) of HIV Ag/Ab and RNA tests compared with adjudicated HIV status. RESULTS: The HIV RNA testing rate for follow-up increased from 16 per 100 person-years (PY) to 123 per 100 PYs after the guideline update. The positivity rate of HIV RNA tests decreased from 1.39% to 0.22%. Overall agreement between Ag/Ab and RNA results remained high. The FPRs of HIV Ag/Ab and RNA testing remained similar, but the PPV of HIV RNA testing for PrEP follow-up decreased from 100% to 67%. We estimated that 8,226 to 9,900 RNA tests would be needed for one HIV diagnosis earlier than would be detected with Ag/Ab testing alone. DISCUSSION: HIV RNA testing did not provide additional value to Ag/Ab testing during routine follow-up of oral PrEP users. Considering the cost and logistical complexity of HIV RNA testing, its use as a routine test during follow-up of oral PrEP users warrants reconsideration.

Antiretroviral therapy (ART) has been adopted as a form of HIV treatment and prevention. This study assesses rapid ART initiation using clinical outcomes such as viral load (VL) and CD4+ T lymphocytes count. Over the course of one year, the progress of newly diagnosed people living with HIV who started ART early in a hospital in Panama City was followed. The evaluation of early initiation of ART in achieving viral suppression (VL <200 copies/ml) was analyzed using descriptive statistics. Additionally, the cost difference between early (first 7 days) and late initiation of ART was evaluated from the perspective of the service provider. In total, 209 people were followed up during the study; 85% were male, 70% started ART on same day from hospital arrival, 80% had suppressed viral load at 6 months, and the median count of CD4 increased from 285 (IQR: 166-429) to 509 (IQR: 373-696) over 12 months. Starting ART early led to a 42% increase for the provider in terms of staffing costs; however, the clients had the opportunity to decrease absenteeism in daily activities. The results reveal that early initiation of ART generates clinical and economic benefits for the person in treatment.

Although lead poisoning can cause detrimental health effects, it is largely preventable. Common exposure sources include contaminated soil, water, and lead-based paint in homes built before the 1978 ban on residential lead-containing paint. In North Carolina, testing for lead is encouraged for all children at ages 1 and 2 years, and is required for children covered by Medicaid. In October 2023, routine pediatric blood lead testing and follow-up investigations conducted by the North Carolina Department of Health and Human Services identified four asymptomatic cases of lead poisoning associated with consumption of cinnamon-containing applesauce packaged in pouches. The Food and Drug Administration (FDA) identified lead in the cinnamon as the source of contamination; chromium was later also detected in the cinnamon. FDA alerted the public on October 28, and the distributor initiated a voluntary recall the following day. To estimate the impact of the event and characterize reported cases, CDC initiated a national call for cases (defined as a blood lead level [BLL] ≥3.5 μg/dL in a person of any age in ≤3 months after consuming a recalled cinnamon-containing applesauce product). During November 22, 2023-April 12, 2024, a total of 44 U.S. states, the District of Columbia, and Puerto Rico reported 566 cases (55% in children aged <2 years, including 20% that were temporally associated with symptoms). The median maximum venous BLL was 7.2 μg/dL (range = 3.5-39.3 μg/dL). The hundreds of children poisoned by this incident highlight the importance of preventing toxic metal contamination of food and promoting routine childhood blood lead testing and follow-up to identify lead exposure sources. Clinicians and public health practitioners should be aware of the potential for exposure to toxic metals from less common sources, including food.

This article assesses the effectiveness of IMC's PDH project by measuring changes in weight-for-age z-score (WAZ) among participating children both during and t 12 months post-implementation. WAZ was the anthropometric indicator of choice, as recommended by PDH guidance (Nutrition Working Group CORE, 2002). This article evaluates changes in nutritional status and seeks to understand caregiver perceptions around implementing promoted practices. Overall, 1,138 children were included in the study (621 Duguna Fango, 517 Damot Woyde), with an average age of 13.5 months (+- 4.8) at enrolment. Within three months of the intervention, 556 (49%) children met the WAZ =-2 criteria. Of the 1,035 children with 12 months of measurements, 472 (46%) achieved normal weight (WAZ =-2) by 12 months of follow-up. The prevalence of severely and moderately underweight children decreased from 36% and 64% (day 1) to 12% and 42% (month 12), respectively. Overall, these findings indicate that weight gain and improvement in WAZ were sustained throughout the 12-month period. Average overall weight gain across the 12 months was 2.55 +- 0.28 kg, with an average change in WAZ of 0.75 +- 0.36 standard deviation. At three months post-intervention, 99% of children met the 0.9 kg weight gain requirement as outlined in PDH protocols. Children who were more severely underweight at enrolment remained underweight by month 12 and had a lag in catch-up growth, compared to those who began the intervention moderately underweight. Although the severely underweight group experienced slightly higher gains over the 12-month period, these gains were often insufficient to reach a normal weight status. This suggests that severely underweight children may require specific, targeted interventions to address their needs.

BACKGROUND: Well designed and properly executed randomised trials are considered the most reliable evidence on the benefits of healthcare interventions. However, there is overwhelming evidence that the quality of reporting is not optimal. The CONSORT (Consolidated Standards of Reporting Trials) statement was designed to improve the quality of reporting and provides a minimum set of items to be included in a report of a randomised trial. CONSORT was first published in 1996, then updated in 2001 and 2010. Here, we present the updated CONSORT 2025 statement, which aims to account for recent methodological advancements and feedback from end users. METHODS: We conducted a scoping review of the literature and developed a project-specific database of empirical and theoretical evidence related to CONSORT, to generate a list of potential changes to the checklist. The list was enriched with recommendations provided by the lead authors of existing CONSORT extensions (Harms, Outcomes, Non-pharmacological Treatment), other related reporting guidelines (TIDieR) and recommendations from other sources (e.g., personal communications). The list of potential changes to the checklist was assessed in a large, international, online, three-round Delphi survey involving 317 participants and discussed at a two-day online expert consensus meeting of 30 invited international experts. RESULTS: We have made substantive changes to the CONSORT checklist. We added seven new checklist items, revised three items, deleted one item, and integrated several items from key CONSORT extensions. We also restructured the CONSORT checklist, with a new section on open science. The CONSORT 2025 statement consists of a 30-item checklist of essential items that should be included when reporting the results of a randomised trial and a diagram for documenting the flow of participants through the trial. To facilitate implementation of CONSORT 2025, we have also developed an expanded version of the CONSORT 2025 checklist, with bullet points eliciting critical elements of each item. CONCLUSIONS: Authors, editors, reviewers, and other potential users should use CONSORT 2025 when writing and evaluating manuscripts of randomised trials to ensure that trial reports are clear and transparent.

Background: The opioid overdose crisis remains a public health concern, and rates of suicide with opioid involvement have increased. Objective: To describe the prevalence of and factors associated with self-reported past 30-day suicide attempt or attempt "only when high or in withdrawal from alcohol or drugs" among reproductive-age women with past 30-day nonmedical prescription opioid use. Methods: Estimates are reported among women 18-55 years from 338 locations in 35 states using 2018-2020 National Addictions Vigilance Intervention and Prevention Program data. Bivariate analysis and multinomial logistic regression identified prevalence of and factors associated with past 30-day suicide attempt and attempt "only when high or in withdrawal from alcohol or drugs." Results: Among 10,095 women, 2.7% reported a past 30-day suicide attempt, and 1.5% reported an attempt "only when high or in withdrawal from alcohol or drugs." The largest magnitude of association for suicide attempt was extreme alcohol problem (adjusted odds ratio [aOR] = 2.84, 95% confidence interval [CI]: 1.80-4.47), and the largest magnitude of association for attempt "only when high or in withdrawal from alcohol or drugs" was no stable living arrangement (aOR = 2.66, 95% CI: 1.78-3.98). Conclusion: Comprehensive, upstream suicide prevention initiatives and substance use treatment can address factors associated with suicide attempt among reproductive-age women.

Marburg virus (MARV) and Ravn virus (RAVV), the only two known members of the species Orthomarburgvirus marburgense (family Filoviridae), are causative agents of Marburg virus disease, a severe viral disease that typically emerges in sub-Saharan Africa and is characterized by human-to-human transmission and high case fatalities. Despite the robust characterization of MARV experimental infection in Egyptian rousette bats (ERBs; Rousettus aegyptiacus; common name: Egyptian rousettes), a natural MARV reservoir, experimental infection with RAVV in ERBs has not been completed. Here, we experimentally infect 12 ERBs with RAVV and quantify viral loads in blood, oral swabs, and rectal swabs over a 21-day timeline with serological and cumulative shedding data and baseline clinical parameters. Compared to previously described experimental MARV infection in ERBs, these bats experimentally inoculated with RAVV had significantly higher and prolonged rectal viral shedding loads, as well as significantly prolonged oral shedding and higher peak viremia. All ERBs seroconverted by 21 days post-infection. Additionally, all ERBs demonstrated marked heterogeneity in RAVV viral shedding loads consistent with the Pareto Principle and viral "supershedders." Our results introduce the possibility of variation in transmission dynamics and subsequent spillover differences between RAVV and MARV.IMPORTANCERavn virus, along with Marburg virus, causes severe viral disease in humans with high fatality but little to no clinical disease in its reservoir host, the Egyptian rousette bat. Our findings provide important insights into how Ravn virus behaves in its natural reservoir host, showing that Ravn virus infection followed a similar timeline to Marburg virus infection, with virus detected in blood, saliva, and feces. However, Ravn virus-infected bats had higher levels of viral shedding and shed the virus for a longer period, particularly in feces, compared to Marburg virus. These differences in viral shedding may impact the spread of the virus within bat populations and potentially alter the likelihood of spillover into humans, non-human primates, and other animal species. These insights are crucial for understanding Ravn virus maintenance in its bat reservoir and improving our ability to mitigate or prevent future human outbreaks.

Same-day pre-exposure prophylaxis for HIV (PrEP) is recommended to improve access to this important HIV prevention tool. A PrEP program at a community-based LGBTQ+ clinic in Seattle, Washington provided PrEP via telemedicine with a focus on converting testing-only visits to same-day 'Insta-PrEP' visits. We identified three key barriers to same-day PrEP for clients who present to clinic for testing-only visits: delays related to health insurance; longer counseling times; and disruption of clinic flow following Insta-PrEP visits. Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.

IMPORTANCE: Well-designed and properly executed randomized trials are considered the most reliable evidence on the benefits of health care interventions. However, there is overwhelming evidence that the quality of reporting is not optimal. The CONSORT (Consolidated Standards of Reporting Trials) statement was designed to improve the quality of reporting and provides a minimum set of items to be included in a report of a randomized trial. CONSORT was first published in 1996, then updated in 2001 and 2010. Herein, we present the updated CONSORT 2025 statement, which aims to account for recent methodological advancements and feedback from end users. OBSERVATIONS: We conducted a scoping review of the literature and developed a project-specific database of empirical and theoretical evidence related to CONSORT to generate a list of potential changes to the checklist. The list was enriched with recommendations provided by the lead authors of existing CONSORT extensions (harms, outcomes, nonpharmacological treatment), other related reporting guidelines (Template for Intervention Description and Replication [TIDieR]), and recommendations from other sources (eg, personal communications). The list of potential changes to the checklist was assessed in a large, international, online, 3-round Delphi survey involving 317 participants and discussed at a 2-day online expert consensus meeting of 30 invited international experts. We have made substantive changes to the CONSORT checklist. We added 7 new checklist items, revised 3 items, deleted 1 item, and integrated several items from key CONSORT extensions. We also restructured the CONSORT checklist, with a new section on open science. The CONSORT 2025 statement consists of a 30-item checklist of essential items that should be included when reporting the results of a randomized trial and a diagram for documenting the flow of participants through the trial. To facilitate implementation of CONSORT 2025, we have also developed an expanded version of the CONSORT 2025 checklist, with bullet points eliciting critical elements of each item. CONCLUSIONS AND RELEVANCE: Authors, editors, reviewers, and other potential users should use CONSORT 2025 when writing and evaluating manuscripts of randomized trials to ensure that trial reports are clear and transparent.

BACKGROUND: Monitoring temporal trends in firearm injury-related emergency department (ED) visits is challenging because traditional surveillance systems lack detailed temporal information. OBJECTIVE: To describe temporal patterns of ED visits for firearm injury using data from the Centers for Disease Control and Prevention's (CDC) Firearm Injury Surveillance Through Emergency Rooms (FASTER) program. DESIGN: Cross-sectional analysis of firearm injury-related ED visits. SETTING: 9 states (Florida, Georgia, New Mexico, North Carolina, Oregon, Utah, Virginia, Washington, and West Virginia) and the District of Columbia from 1 January 2018 to 31 August 2023. PATIENTS: ED visits for firearm injury (n = 93 022) from CDC's FASTER program. MEASUREMENTS: ED visits for firearm injury per 100 000 ED visits, analyzed by time of day (in 30-minute intervals), day of the week, day of the year, and holidays. RESULTS: From January 2018 through August 2023, there were 93 022 firearm injury ED visits (73.9 per 100 000 ED visits), or approximately 1 firearm injury every 30 minutes overall. Rates of firearm injury ED visits were highest between 2:30 and 3:00 a.m. and lowest between 10:00 and 10:30 a.m. Nighttime peaks and daily rates were highest on Friday and Saturday. Monthly rates were highest in July and lowest in February; daily rates were disproportionately high on most holidays, especially Independence Day and New Year's Eve. LIMITATIONS: Data are limited to 9 states and the District of Columbia and are not nationally representative. The analysis of ED visits for firearm injury does not distinguish injury intent and is based on arrival time rather than actual injury time. CONCLUSION: Distinct temporal patterns in firearm injury ED visits highlight resource allocation considerations for prevention and response efforts. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

BACKGROUND: We describe prescribing and dispensing patterns of influenza antivirals among patients with laboratory-confirmed influenza within U.S. urgent care and emergency department settings. METHODS: A retrospective cross-sectional study was conducted for encounters from four large, integrated health systems participating in the VISION network of adult patients presenting with acute respiratory illness to urgent cares or emergency departments and with positive influenza virus test results during the 2023-2024 influenza season. The analysis was restricted to adult patients at higher risk of influenza complications based on presence of underlying medical conditions, older age, pregnancy, and severe obesity. We calculated proportions and odds of prescribed and dispensed antivirals by demographic and clinical characteristics. RESULTS: A total of 10,700 patient encounters were eligible for analysis. Among encounters with a positive standard molecular influenza test result (N=5,231), 58% (range across sites: 47-64%) were prescribed antivirals, with 67% of prescribing occurring on the encounter date. Among those prescribed antivirals (N=3,050), 80% (range across sites: 75-91%) had them dispensed, with 65% of dispensing occurring on the prescription date. Encounters among persons aged ≥65 years had lower odds of same-day prescribing (0.57 [95% CI: 0.42-0.78]) and lower odds of same-day dispensing (0.58 [95% CI: 0.36-0.94]) compared to those 18-49 years. CONCLUSIONS: Gaps in antiviral treatment within urgent care and emergency department settings remain for patients at higher risk of influenza complications, notably among older adults. Strategies to improve earlier initiation of antiviral treatment may help reduce the risk of influenza-associated complications.

OBJECTIVES: To systematically review literature on whether hormonal contraception following ulipristal acetate (UPA) for emergency contraception decreases the effectiveness of either drug. STUDY DESIGN: We searched multiple databases through December 2022 for studies assessing the interaction between UPA and hormonal contraception. The primary outcome was contraceptive effectiveness, measured by pregnancy rates or proxy measures (e.g., ovarian activity). We extracted and summarized findings from identified studies, assessed risk of bias for each study, and determined certainty of evidence for all outcomes. RESULTS: Four studies met inclusion criteria; all had low risk of bias. Two studies assessed whether UPA use affected the ability of oral contraceptives (OCs) to inhibit ovulation; no differences were observed in ovarian activity when starting OCs one day after UPA compared with starting OCs one day after placebo. Two studies assessed whether OC use affected the ability of UPA to delay ovulation; both studies observed higher proportions of ovulation when UPA was followed by OC use versus delayed or no OC use. One study assessed ovulation risk when UPA was taken after missed OCs, followed by immediate versus delayed OC resumption; no ovulations occurred within the first five days after UPA administration in either group, but there was greater risk of ovulation beyond five days with delayed versus immediate OC resumption. CONCLUSIONS: While there is no evidence that UPA affects the ability of hormonal contraception to inhibit ovulation, hormonal contraception use immediately or soon after UPA may decrease UPA's ability to delay ovulation. The certainty of evidence ranged from moderate to very low. IMPLICATIONS: If a patient desires hormonal contraception after UPA, an interaction with UPA can be avoided by delaying initiation or resumption of hormonal contraception. The risk of pregnancy due to decreased effectiveness of UPA with immediate hormonal contraception should be balanced against the risk of subsequent pregnancy due to delay or non-start of hormonal contraception.

PURPOSE: The 2018 Kenya Population-based HIV Impact Assessment revealed gaps in HIV care among adolescents and young people living with HIV (AYPLHIV) aged 10-24 years, with only 70.6% aware of their status, of these, 93.1% on antiretroviral therapy (ART), and 79.2% of those on treatment had achieved viral load suppression (VLS). Operation Triple Zero (OTZ) aims to address these gaps by fostering intrinsic motivation in AYPLHIV to achieve good health outcomes, emphasizing zero missed appointments, zero missed medication, and zero viral load. We examine clinical outcomes of VLS, ART adherence, and retention among AYPLHIV aged 10-24 enrolled in OTZ from 2017 to 2021. METHODS: Data from 20 early adopter OTZ sites were analyzed for ART adherence, retention, viral load testing, and VLS. We compared demographic and clinical characteristics at enrollment and end line by sex, using Pearson's chi-square test for categorical variables, McNemar chi-square test, and Wilcoxon rank-sum for baseline versus end-line comparisons. RESULTS: Of 1,569 AYPLHIV enrolled in OTZ, 1,372 (87.4%) had complete records. The median age at OTZ enrollment was 12 years (interquartile range: 14-16). VLS improved from 72.7% to 88.5% (p < .001), and 96% of AYPLHIV were retained on ART. Among virally suppressed AYPLHIV at baseline (n = 958), 92.4% sustained VLS (91.9% females, 92.9% males), notably 100% among those on once-a-day dolutegravir or atazanavir. Re-suppression rate for viremic AYPLHIV at baseline (n = 360) was 78.3%. Satisfactory adherence correlated with higher re-suppression rates. DISCUSSION: OTZ implementation led to improved HIV treatment outcomes among AYPLHIV, contributing to sustained epidemic control efforts complementing other interventions.

BACKGROUND: Achieving adequate mass drug administration (MDA) coverage for lymphatic filariasis is challenging. We sought to improve stakeholder engagement in MDA planning and increase subsequent MDA coverage through a series of microplanning workshops. METHODOLOGY: Prior to the 2018 MDA, Haiti's Ministry of Public Health and Population (MSPP) and partners conducted 10 stakeholder microplanning workshops in metropolitan Port-au-Prince. The objectives of the workshops were to identify and address gaps in geographic coverage of supervision areas (SAs); review past MDA performance and propose strategies to improve access to MDA; and review roles and responsibilities of MDA personnel through increased stakeholder engagement. Retrospective pre-testing was employed to assess the effectiveness of the workshops. Participants used a 5-point scale to rank their understanding of past performance, SA boundaries, roles and responsibilities, and their perceived engagement by MSPP. Participants simultaneously ranked their previous year's attitudes and their attitudes about MDA following the 2-day microplanning workshop. Changes in pre- and post-scores were analyzed using Wilcoxon signed-rank tests. PRINCIPAL FINDINGS: A total of 356 stakeholders across five communes participated in the workshops. Participants conducted various planning activities, including revising SA boundaries to ensure full geographic reach of MDA, proposing or validating social mobilization strategies, and proposing other MDA improvements. Compared with previous year rankings, the workshops increased participant understanding of past performance by 1.34 points (standard deviation [SD] = 1.05, p <0.001); SA boundaries by 1.14 points (SD = 1.30; p <0.001); their roles and responsibilities by 0.71 points (SD = 0.95, p <0.001); and sense of engagement by 1.03 points (SD = 1.08, p <0.001). Additionally, compared with 2017, drug coverage increased in all five communes during the 2018 MDA.

Human health may benefit from exposure to a class of biogenic volatile organic compounds (BVOCs) consisting of isoprene units, known as terpenes. In this double-blind, randomized crossover trial, participants sat in a forest for two 60-minute sessions, one in which terpenes were filtered out of the ambient air they breathed, and another in which they were not, separated by a minimum of an eight-day washout period. The primary outcome was the high frequency (HF) component of heart rate variability (HRV; measured continuously). Secondary outcomes included skin conductance levels (SCL) (measured continuously), self-reported stress and affect (measured every 20 minutes), blood pressure, heart rate, cortisol and inflammatory cytokines (measured before and after sessions). Serum concentrations of terpenes (measured before and after sessions) were also assessed to investigate the association of absorbed dose with these outcomes. We did not observe a significant association of filter condition with most outcomes; although the trends for affect, systolic blood pressure, cortisol, TNF-α, and CRP were all in the hypothesized direction. We did observe a significant association with interleukin-6, which was -0.19 pg/mL lower in the terpenes-on vs. terpenes-off condition, adjusted for baseline (95% CI: -0.35, -0.03); and SCL over the session as a whole. A sensitivity analysis of the subset of data from participants who completed both conditions supports these findings and revealed additional significant associations with SCL (95% CI: -0.35, -0.02); and TNF-α (95% CI: -2.63, -0.01). To our knowledge, this is the first RCT to filter ambient air from terpenes during forest contact.

OBJECTIVE: To describe awareness of ambient wildfire smoke among U.S. adults with and without asthma. METHODS: We analyzed data from the summer wave of the 2021 ConsumerStyles survey, a nationally representative survey of 4,085 U.S. adults. Respondents self-reported their asthma status and awareness of wildfire smoke where they lived in the past 12 months. We linked survey responses by zip code of residence with satellite-detected wildfire smoke plume data that estimated the daily maximum smoke plume density over the preceding year. We estimated associations between asthma status and awareness of wildfire smoke across categories of maximum smoke plume density and days with medium- or heavy-density smoke as prevalence ratios (PRs) with 95% confidence intervals (CIs) using predicted marginal probabilities from logistic regression models. RESULTS: Over 98% of the estimated population of U.S. adults lived in a zip code affected by ≥1 day of medium- or heavy-density wildfire smoke, which occurred on an average of 16 days in the past year. Awareness of wildfire smoke was reported by 19% of U.S. adults and was higher among adults with than without asthma (PR: 1.25; 95% CI: 1.01, 1.55), including in zip codes affected by heavy-density smoke (PR: 1.30, 95% CI: 1.04, 1.63) and with 22 or more days of medium- to heavy-density smoke (PR: 1.22, 95% CI: 1.01, 1.47). CONCLUSIONS: Although awareness of wildfire smoke was higher among U.S. adults with than without asthma, low percentages of awareness overall indicate a need for health communication about wildfire smoke and its health risks.

BACKGROUND: Wastewater-based surveillance is an important tool for monitoring the COVID-19 pandemic. However, it remains challenging to translate wastewater SARS-CoV-2 viral load to infection number, due to unclear shedding patterns in wastewater and potential differences between variants. OBJECTIVES: We utilized comprehensive wastewater surveillance data and estimates of infection prevalence (i.e., the source of the viral shedding) available for New York City (NYC) to characterize SARS-CoV-2 fecal shedding pattern over multiple COVID-19 waves. METHODS: We collected SARS-CoV-2 viral wastewater measurements in NYC during August 31, 2020 - August 29, 2023 (N = 3794 samples). Combining with estimates of infection prevalence (number of infectious individuals including those not detected as cases), we estimated the time-lag, duration, and per-infection fecal shedding rate for the ancestral/Iota, Delta, and Omicron variants, separately. We also developed a procedure to identify occasions with intensified transmission. RESULTS: Models suggested fecal viral shedding likely starts around the same time as and lasts slightly longer than respiratory tract shedding. Estimated fecal viral shedding rate was highest during the ancestral/Iota variant wave, at 1.44 (95% CI: 1.35 - 1.53) billion RNA copies in wastewater per day per infection (measured by RT-qPCR), and decreased by around 20% and 50-60% during the Delta wave and Omicron period, respectively. We identified around 200 occasions during which the wastewater SARS-CoV-2 viral load exceeded the expected level in any of the city's 14 sewersheds. These anomalies disproportionally occurred during late January, late April-early May, early August, and from late-November to late-December, with frequencies exceeding the expectation assuming random occurrence (P < 0.05; bootstrapping test). DISCUSSION: These estimates may be useful in understanding changes in underlying infection rate and help quantify changes in COVID-19 transmission and severity over time. We have also demonstrated that wastewater surveillance data can support the identification of time periods with potentially intensified transmission.

IMPORTANCE: Neonates requiring intensive care are at high risk of health care-associated infections. In neonatal intensive care units (NICUs) in low-resource settings, the identification of modifiable risk factors can inform targeted prevention strategies to reduce the global burden of neonatal morbidity and mortality. OBJECTIVE: To describe the incidence of and the risk factors associated with health care-associated bloodstream infections (BSIs) in NICUs in Pune, India. DESIGN, SETTING, AND PARTICIPANTS: This multicenter prospective cohort study enrolled all neonates admitted to 3 NICUs in Pune, India, from May 1, 2017, to July 31, 2019. Neonates were followed up from admission until discharge, transfer, or death. This secondary data analysis included neonates admitted for 3 days or more and was completed on January 31, 2024. MAIN OUTCOMES AND MEASURES: The primary outcome was health care-associated BSIs, defined as a positive blood culture on or after admission day 3. Summary statistics, incidence of health care-associated BSIs, and hazard rate by characteristics of interest were generated. Among neonates admitted for 7 days or longer, the association between antibiotic exposure and infection risk was assessed. RESULTS: A total of 6410 neonates were admitted for 3 days or longer. The median gestational age was 34 weeks (IQR, 32-37 weeks), and 3560 (55.5%) were male. The incidence of health care-associated BSIs was 6.09 per 1000 patient-days. Most isolates were gram-negative organisms (n = 273 [66.3%]), of which 85.5% (202 of 236 isolates tested) were resistant to third- or fourth-generation cephalosporins and 44.8% (117 of 261 isolates tested) were resistant to carbapenems. The hazard rate of health care-associated BSIs was higher among neonates with central venous catheters, respiratory support, or urinary catheters within 3 days preceding infection. Of 3229 neonates admitted for 7 days or longer, 190 (5.8%) had health care-associated BSIs on or after hospital day 7, with an incidence of 3.22 per 1000 patient-days. Antibiotic exposure during the first week of admission was associated with a nearly 3-fold increase in the risk of health care-associated BSIs (adjusted hazard ratio, 2.82 [95% CI, 1.26-6.32]). CONCLUSIONS AND RELEVANCE: In this cohort study of 6410 neonates admitted to 3 NICUs in Pune, India, the risk of health care-associated BSIs was associated with the presence of indwelling devices and prior antibiotic exposure. Future efforts should focus on mitigating the risks associated with indwelling devices and strengthening infection prevention and control and antimicrobial stewardship programs to prevent health care-associated infections.

BACKGROUND: Nursing home residents experience a large burden of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections. Data are limited regarding nursing home characteristics associated with differences in facility-level invasive MRSA rates. METHODS: We analyzed 2011-2015 data from CDC's Emerging Infections Program (EIP) active population- and laboratory-based surveillance for invasive MRSA cases within seven states. A nursing home-onset case was defined as MRSA cultured from a normally sterile site in a person living in a nursing home 3 days before culture collection. Facility rates were calculated as nursing home-onset cases per 100,000 resident-days. Nursing home resident-day denominators and facility characteristics were obtained from four Centers for Medicare & Medicaid Services (CMS) datasets. A general estimating equations model with a logit link assessed characteristics of the facilities with highest rates comprising 50% of nursing home MRSA cases ("high rates"). RESULTS: The 626 nursing homes in the surveillance area had 2824 invasive MRSA cases; 82% of facilities had at ≥1 case. The 20% of facilities with highest rates (≥3.84 cases/100,000 resident-days) had 50% of nursing home-onset cases. In multivariable regression, facilities with high rates were more likely to have CMS-derived characteristics of presence of a resident with a multidrug-resistant organism; or greater proportions of residents who were male, were short stay (in the facility <100 days), had a nasogastric or percutaneous gastrostomy tube, or require extensive assistance with bed repositioning; and more likely to be in an EIP area with higher hospital-onset MRSA rates. Higher registered nurses staffing levels (hours/resident/day) and higher proportions of White residents were associated with lower rates. CONCLUSIONS: Facilities with higher invasive MRSA rates served residents with more clinical and functional care needs. Increasing registered nurse staffing in high-risk facilities might assist with reduction of invasive MRSA rates. These findings could help prioritize nursing homes for future MRSA prevention work.

Pre-exposure prophylaxis (PrEP) is an effective tool in protecting persons from acquiring HIV infection through sex or injection drug use. However, awareness and willingness to use PrEP among Black gay, bisexual, and other men who have sex with men (BMSM) remain suboptimal compared to White MSM (WMSM) in the United States. Our aims were to (1) assess the factors associated with PrEP awareness and willingness to use PrEP among MSM and (2) compare the PrEP perceptions among BMSM versus non-Black MSM. Data were drawn from two cross-sectional behavioral surveys in Baltimore, MD: Behavioral Surveillance Research (BESURE) conducted in 2017, and Safe Spaces 4 Sexual Health (SS4SH), conducted in 2018 and 2019. Descriptive statistics were used to summarize the study population. We used Poisson regression models to identify variables associated with awareness of PrEP and willingness to use PrEP. PrEP perceptions were assessed via 13 items scored on a 5-point Likert scale. Finally, we conducted a post-hoc exploratory bivariate analysis of the relationship between PrEP perception and willingness to use PrEP, stratified by race/ethnicity. A total of 261 MSM participated in this study. Many of the participants were aware of PrEP (75.1%). Factors associated with greater PrEP awareness included having greater than a high school education (aRR 1.22, 95% CI 1.04, 1.43); and earning more than $25,000 annually (aRR 1.24, 95% CI 1.08, 1.42). Participants who had received money in exchange for sex one or more times were less likely to be aware of PrEP (aRR 0.59, 95% CI 0.36, 0.95). More than half of the participants were willing to use PrEP (55.3%). In bivariate and multivariable analyses, demographic or behavioral characteristics were not significantly associated with willingness to use PrEP. Higher agreement with the following statements was associated with lower willingness to use PrEP: "Having to take a pill every day is difficult" (RR 0.89, 95% CI 0.82-0.97) and, "I am concerned about the side effects of PrEP" (RR 0.89, 95% CI 0.82-0.96), and "PrEP is for people who have riskier sex lives than I do" (RR 0.86, 95% CI 0.78-0.95). Conversely, higher willingness to use PrEP was associated with comfortable having sex without a condom (RR 1.11, 95% CI 1.02-1.21), less anxious about sex (RR 1.12, 95% CI 1.02-1.24), and my friends think that I should take PrEP (RR 1.19, 95% CI 1.07-1.32). We found BMSM compared to non-Black MSM had higher mean scores related to taking a daily pill (p = 0.041), concerns about side effects (p = 0.012), concerns about people thinking they had HIV (p = 0.001), concerns about the financial costs of PrEP (p = 0.038) and caution when dealing with healthcare organizations/medical mistrust (p = 0.019). Perceptions with a statistically significant lower score among BMSM versus non-Black MSM included statements such as, comfortable having sex without a condom (p = 0.003) and less anxious about sex (p < 0.001). We conclude HIV prevention strategies, programs, and interventions should be cognizant of PrEP perceptions that facilitate or hinder PrEP uptake in Baltimore City, MD.

IMPORTANCE: Antimicrobial resistance is a major public health problem in the US. Estimating national rates of antimicrobial-resistant infections commonly associated with health care can aid in targeted public health efforts. OBJECTIVE: To determine the national incidence rates of 6 pathogens over time: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp (VRE), extended-spectrum cephalosporin-resistant Escherichia coli and Klebsiella spp (excluding Klebsiella aerogenes) (ESCR-EK), carbapenem-resistant Enterobacterales (CRE), carbapenem-resistant Acinetobacter spp (CRAsp), and multidrug-resistant (MDR) Pseudomonas aeruginosa. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from 2012 to 2022 on inpatient hospitalizations, clinical cultures, and facility-level characteristics. Hospital-months were included in the dynamic cohort if the hospital reported at least 1 culture with microbial growth accompanied by antimicrobial susceptibility testing (AST) results in the month. Data from the PINC-AI and Becton Dickinson Insights databases were used, and cases were defined as incident nonsurveillance cultures yielding an organism of interest with sufficient AST results for a phenotype of interest. Data were collected from January 2012 to December 2022 and analyzed from April 2023 to June 2024. EXPOSURE: Inpatient hospitalizations with a discharge date in an included hospital month. MAIN OUTCOMES AND MEASURES: National annual antimicrobial-resistant cases per 10 000 hospitalizations were obtained using weights based on facility-level characteristics. Cases were defined as community-onset if collected on or before day 3 of hospitalization and hospital-onset if obtained on day 4 or later. RESULTS: This study cohort included 332 to 606 hospitals per year between 2012 to 2022 and 7 158 139 cultures. Antimicrobial-resistant pathogens accounted for an estimated 569 749 (95% CI, 475 949-663 548) cases and 179.6 (95% CI, 163.1-196.1) cases per 10 000 hospitalizations in 2022. Of these cases, 77% (437 657; 95% CI, 364 529-510 785) were community-onset and 23% (132 092; 95% CI, 108 241-155 943) were hospital-onset. MRSA (44% [251 854; 95% CI, 209 558-294 150]) and ESCR-EK (35% [200 884; 95% CI, 163 692-238 077]) made up the largest proportions of total infections in 2022, respectively. Rates of hospital-onset MRSA, VRE, CRE, CRAsp, and MDR P aeruginosa had periods of decline from 2012 to 2019; however, all pathogens experienced an increase in hospital-onset rates in 2020 and 2021. Community-onset ESCR-EK rates increased from 2012 to 2022, while community-onset rates of MRSA, VRE, and MDR P aeruginosa declined. CONCLUSIONS AND RELEVANCE: While antimicrobial resistance rates have experienced uneven declines in the US from 2012 to 2022, the burden of resistance remains substantial. These findings suggest that more effective strategies to reduce antimicrobial resistance are needed.

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

BACKGROUND: Dentists, dental hygienist, and veterinary technicians using drills, scalers and polishers are at risk of developing sensorineural deficits in the fingers and hands. The goal of this study was to determine whether exposure to high-frequency vibration contributed to changes in sensory function. METHODS: The tails of rats were exposed to vibration at 1250 Hz (constant acceleration of 49 m/s2) for 4 hours per day, for 10 days. The effects on sensory nerve function, and vascular function were measured. RESULTS: Vibration increased sensitivity to applied pressure and to transcutaneous electrical stimulation at 2000 and 250 Hz. It also resulted in a reduction in blood flow and myogenic tone. CONCLUSIONS: Exposure to high-frequency vibration has detrimental effects on both peripheral sensorineural and vascular function.