BACKGROUND AND OBJECTIVES: Fungal infections cause substantial morbidity and mortality. Monitoring antifungal use is a foundational aspect of antifungal stewardship, particularly as new disease-causing fungi emerge and antifungal resistance spreads. We assessed recent patterns in systemic antifungal medication use among hospitalized patients within a diverse convenience sample of academic medical centres and community hospitals in the USA. METHODS: We conducted a multicentre retrospective cohort study using the Vizient(R) Clinical Data Base. We selected hospitalized patients who received >/=1 dose of systemic antifungal medication during 2018-23 and assessed antifungal days of therapy (DOT) per 1000 patient days. We stratified antifungal DOT by National Comprehensive Cancer Network (NCCN) cancer centre status to compare antifungal use at hospitals with an NCCN-designated cancer centre-some of which also include a main academic medical centre and non-cancer service lines-versus hospitals without an NCCN-designated cancer centre. RESULTS: Among 39 956 873 discharges from 412 hospitals, the proportion of patients who received any systemic antifungal was 4.5%; azoles (3.8%) were the most common antifungal class, followed by echinocandins (0.9%). Overall antifungal DOT were 53.7 per 1000 patient days (114.5 among 25 NCCN hospitals and 43.2 among 387 non-NCCN hospitals). CONCLUSIONS: Substantial antifungal use occurs among hospitalized patients, particularly among those with cancer. The growing population susceptible to fungal infections (e.g. transplants, cancer and other immunosuppressing conditions) warrants consideration of antifungal stewardship and evaluation of appropriateness of antifungal use in the context of increasing resistance.

Baylisascaris procyonis (raccoon roundworm), a parasite commonly found in raccoons (Procyon lotor), can cause severe disease in humans when it invades visceral organs or the ocular and central nervous systems. Without prompt treatment, B. procyonis infection can lead to serious complications and death. During September 2024, the Los Angeles County Department of Public Health was notified of two unrelated pediatric patients with neurologic signs and symptoms consistent with baylisascariasis, including behavioral change, lethargy, and gait instability. The first case occurred in an adolescent aged 14 years who had received a previous diagnosis of autism spectrum disorder and had a history of pica (i.e., ingestion of nonfood items); the second case occurred in a previously healthy child aged 15 months. Both were treated with albendazole and corticosteroids. The first patient returned to baseline neurologic status, but delays in diagnosis and treatment of the second patient resulted in severe neurologic sequelae. Epidemiologic investigations identified raccoon feces that had fallen from a rooftop latrine (i.e., a communal raccoon defecation site) as the possible source of exposure for the adolescent. No source of exposure was identified for the younger child. B. procyonis infection should be suspected and prompt treatment considered in patients with neurologic symptoms and cerebrospinal fluid or peripheral blood eosinophilia (>1,000 eosinophils/mL of blood), especially young children or persons with developmental disabilities or pica. In addition, the public should be aware of exposure prevention strategies, including preventing raccoon activity around properties, avoiding exposure to raccoon feces, and safely removing raccoon latrines.

IMPORTANCE: The mandatory service of essential workers during the COVID-19 pandemic was associated with high job stress, increased SARS-CoV-2 exposure, and limited time for recovery following infection. Understanding outcomes for frontline workers can inform planning for future pandemics. OBJECTIVE: To compare patient-reported outcomes by employment type and SARS-CoV-2 status. DESIGN: Data from the INSPIRE registry, which enrolled COVID-positive and COVID-negative adults between 12/7/2020-8/29/2022 was analyzed. Patient-reported outcomes were collected quarterly over 18 months. SETTING: Participants were recruited across eight US sites. PARTICIPANTS: Employed INSPIRE participants who completed a short (3-month) and long-term (12-18 month) survey. EXPOSURE: SARS-CoV-2 index status and employment type (essential healthcare worker [HCW], essential non-HCW, and non-essential worker ["general worker"]). MAIN OUTCOMES AND MEASURES: PROMIS-29 (mental and physical health summary) and PROMIS Cognitive SF-CF 8a (cognitive function) scores were assessed at baseline, short-term (3-months), and long-term (12-18 months) timepoints using GEE modeling. RESULTS: Of the 1,463 participants: 53.5% were essential workers (51.4% HCWs, 48.6% non-HCWs) and 46.5% were general workers. Most associations between outcomes and employment type became non-significant after adjusting for sociodemographics, comorbidities, COVID-19 vaccination, and SARS-CoV-2 variant period. However, among COVID-negative participants, essential HCWs had higher cognitive scores at baseline (β: 3.91, 95% CI [1.32, 6.50]), short term: (β: 3.49, 95% CI: [0.80, 6.18]) and long-term: (β: 3.72, 95% CI: [0.98, 6.46]) compared to general workers. Among COVID-positive participants, essential non-HCWs had significantly worse long-term physical health summary scores (β:-1.22, 95% CI: [-2.35, -0.09]) compared to general workers. CONCLUSIONS AND RELEVANCE: Differences in outcomes by worker status were largely explained by baseline characteristics. However, compared to general workers, essential HCW status had higher cognitive function in the absence of SARS-CoV-2 infection at all timepoints, while essential non-HCWs were most vulnerable to poor recovery in long-term physical health following SARS-CoV-2 infection. Preparation efforts for future pandemics may consider enhanced protection and post-infection resources for frontline workers.

INTRODUCTION: This study examined the prevalence and correlates of 6 healthy behaviors among preschool-age children in the United States. METHODS: Data from the 2021 and 2022 National Survey of Children's Health were used to examine daily fruit consumption, daily vegetable consumption, no sugary beverage consumption in the past week, frequent outdoor play (≥2 hours/day), limited screen time (≤1 hour/weekday), and adequate sleep (≥10 hours/day) among children ages 3-5 years (N=23,123). Relationships between healthy behaviorss and child, family, community characteristics, and state of residence were examined using logistic regression modeling, accounting for the complex survey design. Analyses were conducted in 2024 using SAS-callable SUDAAN. RESULTS: Prevalence of healthy behaviors varied from 32.4% having no sugary drinks in the past week to 65.3% eating fruit daily. Only 20% engaged in all or nearly all (5-6) healthy behaviors. After adjustment, children engaging in 5-6 HBs were more likely to be younger, non-Hispanic White, have parents with higher education and income, excellent/very good parental mental health, frequent family meals, household food sufficiency, and live in safe neighborhoods, yet prevalence rose to only 30% across any characteristic. The proportion of children engaging in 5-6 healthy behaviors ranged from 6.5% in Mississippi to 46.4% in Vermont, with child, family, and community factors accounting for 43% of the variance between states. CONCLUSIONS: There is a need to increase healthy behaviors among preschool-age children and address disparities. Family and community factors associated with healthy behaviors can inform pediatric care, public policy, programmatic investments, and additional research to foster improvement.

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

OBJECTIVE: ADHD is a commonly diagnosed neurodevelopmental disorder in the U.S., with symptoms including hyperactivity, inattention, and impulsivity. These symptoms can lead to increased engagement in unhealthy behaviors. The current study examined the associations between health risk factors and ADHD among a community-based sample of 345 students (4th-12th grade) by ADHD alone or with co-occurring disorders, ADHD medication use, and ADHD symptom count. Distinct from prior studies, our analysis also examined associations among pairs of health risk factors by ADHD diagnostic criteria. METHOD: Data came from the Replication Project to Learn About Youth-Mental Health, using a two-stage design, incorporating teacher, parent, and student reported data. RESULT: Students with ADHD experienced a higher prevalence of not using a bike helmet (prevalence ratio [PR] = 1.17, 95% confidence interval [CI] [1.01, 1.35]), being bullied, threatened, or feeling unsafe at school (PR = 1.83, 95% CI [1.02, 3.30]) carrying a weapon (PR = 7.02, 95% CI [2.58, 19.08]), and feeling sad or hopeless within the past 2 weeks (PR = 2.74, 95% CI [1.01, 7.47]) compared to those with no disorder. Students with ADHD exhibited different risk associations compared to those with no disorder, specifically for interpersonal violence risk. Medication treatment for ADHD was not associated with fewer health risks, except that students taking ADHD medication were less likely to skip breakfast (PR = 0.40, 95% CI [0.20, 0.78]) compared to those without ADHD. Higher ADHD symptom counts were associated with elevated television screen time, stimulant medication misuse, physical fight involvement, and carrying a weapon (p < .05). CONCLUSION: Evaluating participation in health risk factors and developing tailored interventions may benefit youth with ADHD, regardless of treatment status.

BACKGROUND: Plasmodium falciparum multidrug resistance transporter 1 (Pfmdr1) gene mutations are associated with altered response to artemisinin-based combination therapy (ACT), particularly the combinations containing the partner drugs lumefantrine and amodiaquine (i.e., artemether-lumefantrine [AL] and artesunate-amodiaquine [ASAQ]). Past studies of Pfmdr1 single nucleotide polymorphisms (SNPs) at codons 86, 184, and 1246 have shown different responses to AL and ASAQ. METHODS: To determine whether infection with parasites carrying specific Pfmdr1 SNPs leads to increased risk of recurrent parasitaemia (recrudescent or new infection), data from 3,915 samples from 16 therapeutic efficacy studies from 13 African countries between 2013 and 2019 were analysed. RESULTS: Patients treated with AL and infected with parasites carrying Pfmdr1 N86 were at greater risk of recurrent infection than those whose parasites carried 86Y. After treatment with ASAQ, individuals infected with parasites that carried Pfmdr1 86Y were more likely to experience a recurrent infection. CONCLUSIONS: These results support prior studies that suggested: (1) patients given AL and infected with parasites carrying N86 were more likely to experience a recurrent infection; (2) patients given ASAQ and infected with parasites carrying 86Y were more likely to experience a recurrent infection. These findings suggest that ACT and Pfmdr1 genotype may influence outcome after Plasmodium falciparum infection.

BACKGROUND: On January 30, 2020, the World Health Organization declared COVID-19 a Public Health Emergency of International Concern (PHIEC). On March 11, 2020, it was characterized as a pandemic, prompting the Government of Sierra Leone to implement response plans. The first case in the country was reported on March 31, 2020. To build resilient public health systems after the Ebola crisis, the Sierra Leone Field Epidemiology Training Program (SLFETP) was launched in 2016 with funding from the U.S. CDC in collaboration with the Ministry of Health and the African Field Epidemiology Network (AFENET). The program started at the FETP Frontline level, a 3-month in-service training program, followed by the FETP Intermediate, a 9-month in-service training program launched in 2017. Both levels adopted the CDC curriculum to the local context. The curriculum consists of classroom modules focusing on surveillance, outbreak investigation, and field projects. The SLFETP graduates and trainees were deployed to assist in COVID-19 response efforts. While reports indicate the SLFETP's contributions to COVID-19 preparedness and response, the specific roles of its graduates and trainees remain undocumented. This paper outlines their crucial involvement during the pandemic in Sierra Leone. METHODS: We reviewed 12 documents from the SLFETP, including work plans, outbreak investigation reports, and success stories, to assess the FETP's contributions during the COVID-19 pandemic. We interviewed graduates and trainees about their roles and conducted discussions with stakeholders and FETP staff to explore the FETP's role during the pandemic's preparedness and response phases. A thematic analysis was performed. RESULTS: The SLFETP played a critical role during the preparedness and response phase of the COVID-19 pandemic. The trainees and graduates enhanced the surveillance system and led key response pillars, such as coordination, surveillance, and quarantine. SLFETP supported districts by building their capacity, especially in the district surveillance pillar, to conduct case investigations, contact tracing, quarantine monitoring, and data management. CONCLUSIONS: The graduates and trainees reportedly played critical roles in key response pillars across the country in the preparedness and response phase of the COVID-19 pandemic. These gains should be maintained and scaled up to build a strong and resilient public health workforce in Sierra Leone, which is crucial for preparedness and response to future outbreaks.

We report 1.3% (19/1,511) of Egyptian rousette bats (ERBs) in Uganda and Sierra Leone were co-infected with different combinations of Marburg, Sosuga, Kasokero, or Yogue viruses. To prevent infection by those viruses, we recommend avoiding ERB-populated areas, avoiding ERBs and ERB-contaminated objects, and thoroughly washing harvested fruits before consumption.

PROBLEM/CONDITION: Autism spectrum disorder (ASD). PERIOD COVERED: 2022. DESCRIPTION OF SYSTEM: The Autism and Developmental Disabilities Monitoring Network is an active surveillance program that estimates prevalence and characteristics of ASD and monitors timing of ASD identification among children aged 4 and 8 years. In 2022, a total of 16 sites (located in Arizona, Arkansas, California, Georgia, Indiana, Maryland, Minnesota, Missouri, New Jersey, Pennsylvania, Puerto Rico, Tennessee, Texas [two sites: Austin and Laredo], Utah, and Wisconsin) conducted surveillance for ASD among children aged 4 and 8 years and suspected ASD among children aged 4 years. Surveillance included children who lived in the surveillance area at any time during 2022. Children were classified as having ASD if they ever received 1) an ASD diagnostic statement in a comprehensive developmental evaluation, 2) autism special education eligibility, or 3) an ASD International Classification of Diseases, Ninth Revision (ICD-9) code in the 299 range or International Classification of Diseases, Tenth Revision (ICD-10) code of F84.0, F84.3, F84.5, F84.8, or F84.9. Children aged 4 years were classified as having suspected ASD if they did not meet the case definition for ASD but had an evaluator's suspicion of ASD documented in a comprehensive developmental evaluation. RESULTS: Among children aged 8 years in 2022, ASD prevalence was 32.2 per 1,000 children (one in 31) across the 16 sites, ranging from 9.7 in Texas (Laredo) to 53.1 in California. The overall observed prevalence estimate was similar to estimates calculated using Bayesian hierarchical and random effects models. ASD was 3.4 times as prevalent among boys (49.2) than girls (14.3). Overall, ASD prevalence was lower among non-Hispanic White (White) children (27.7) than among Asian or Pacific Islander (A/PI) (38.2), American Indian or Alaska Native (AI/AN) (37.5), non-Hispanic Black or African American (Black) (36.6), Hispanic or Latino (Hispanic) (33.0), and multiracial children (31.9). No association was observed between ASD prevalence and neighborhood median household income (MHI) at 11 sites; higher ASD prevalence was associated with lower neighborhood MHI at five sites.Record abstraction was completed for 15 of the 16 sites for 8,613 children aged 8 years who met the ASD case definition. Of these 8,613 children, 68.4% had a documented diagnostic statement of ASD, 67.3% had a documented autism special education eligibility, and 68.9% had a documented ASD ICD-9 or ICD-10 code. All three elements of the ASD case definition were present for 34.6% of children aged 8 years with ASD.Among 5,292 (61.4% of 8,613) children aged 8 years with ASD with information on cognitive ability, 39.6% were classified as having an intellectual disability. Intellectual disability was present among 52.8% of Black, 50.0% of AI/AN, 43.9% of A/PI, 38.8% of Hispanic, 32.7% of White, and 31.2% of multiracial children with ASD. The median age of earliest known ASD diagnosis was 47 months and ranged from 36 months in California to 69.5 months in Texas (Laredo).Cumulative incidence of ASD diagnosis or eligibility by age 48 months was higher among children born in 2018 (aged 4 years in 2022) than children born in 2014 (aged 8 years in 2022) at 13 of the 15 sites that were able to abstract records. Overall cumulative incidence of ASD diagnosis or eligibility by age 48 months was 1.7 times as high among those born in 2018 compared with those born in 2014 and ranged from 1.4 times as high in Arizona and Georgia to 3.1 times as high in Puerto Rico. Among children aged 4 years, for every 10 children meeting the case definition of ASD, one child met the definition of suspected ASD.Children with ASD who were born in 2018 had more evaluations and identification during ages 0-4 years than children with ASD who were born in 2014 during the 0-4 years age window, with an interruption in the pattern in early 2020 coinciding with onset of the COVID-19 pandemic.Overall, 66.5% of children aged 8 years with ASD had a documented autism test. Use of autism tests varied widely across sites: 24.7% (New Jersey) to 93.5% (Puerto Rico) of children aged 8 years with ASD had a documented autism test in their records. The most common tests documented for children aged 8 years were the Autism Diagnostic Observation Schedule, Autism Spectrum Rating Scales, Childhood Autism Rating Scale, Gilliam Autism Rating Scale, and Social Responsiveness Scale. INTERPRETATION: Prevalence of ASD among children aged 8 years was higher in 2022 than previous years. ASD prevalence was higher among A/PI, Black, and Hispanic children aged 8 years than White children aged 8 years, continuing a pattern first observed in 2020. A/PI, Black, and Hispanic children aged 8 years with ASD were also more likely than White or multiracial children with ASD to have a co-occurring intellectual disability. Identification by age 48 months was higher among children born in 2018 compared with children born in 2014, suggesting increased early identification consistent with historical patterns. PUBLIC HEALTH ACTION: Increased identification of autism, particularly among very young children and previously underidentified groups, underscores the increased demand and ongoing need for enhanced planning to provide equitable diagnostic, treatment, and support services for all children with ASD. The substantial variability in ASD identification across sites suggests opportunities to identify and implement successful strategies and practices in communities to ensure all children with ASD reach their potential.

OBJECTIVE: Promoting health during adolescence can support long-term well-being, especially for teens diagnosed with attention-deficit/hyperactivity disorder (ADHD), who face increased risks due to the disorder's impact on development and health behaviors. ADHD is often associated with difficulties in social interactions, a higher likelihood of bullying involvement, and co-occurring mental health conditions. These factors may also be influenced by health factors such as physical activity, sleep quality, and screen time usage. Nationally representative teen self-reports provide a novel perspective on ADHD-related health outcomes compared with relying on parent reports. METHOD: We used nationally representative data from the National Health Interview Survey (NHIS) and NHIS-Teen from July 2021 to December 2022, to examine teen-reported health and well-being factors, stratified by parent-reported ADHD diagnoses among teens aged 12 to 17 years. Weighted prevalence estimates and adjusted prevalence ratios (aPR) adjusting for teen age, sex, and family income, all with 95% confidence intervals (CIs), were calculated. RESULTS: Just over 10% of teens had ADHD and they reported higher prevalence of bullying victimization (aPR = 1.64, CI = 1.27-2.11), difficulties making friends (aPR = 1.83, CI = 1.15-2.90), difficulty getting out of bed (aPR = 1.29, CI = 1.02-1.64), irregular wake times (aPR = 2.17, CI = 1.45-3.25), and >4 hours daily screen time (aPR = 1.26, CI = 1.05-1.52) than teens without ADHD; teens with ADHD reported a lower prevalence of lacking peer support (aPR = 0.70, CI = 0.51-0.96). CONCLUSION: Teens with ADHD face distinct challenges related to social-emotional well-being and health behaviors that support overall wellness. Findings may inform opportunities for health promotion among teens with ADHD.

BACKGROUND: Malaria transmission in Sierra Leone is intense and perennial, accounting for 40% of clinical consultations. Medical workers diagnose suspected malaria cases using rapid diagnostic tests (RDT) and microscopy, with facility-level results reported to the Health Management Information System (HMIS) as monthly aggregates. Commodity stocks are reported to the Logistics Management Information System (LMIS). Partners investigated a striking increase in confirmed malaria during May-July 2023 in Sierra Leone, peaking in June to 46% above the June 2018-2022 mean. METHODS: The team first analysed national, district, and facility HMIS/LMIS data for RDT stocks, testing rates, and confirmed cases during January 2018-October 2023. Epidemic thresholds, defined as case counts two standard deviations (σ) above the previous 5 years' monthly mean, were assessed. Then four facilities in two districts were visited to interview staff. Lastly, the team reanalysed LMIS RDT stock data for all facilities in Sierra Leone using R to categorize their stock status by month. RESULTS: National epidemic thresholds were surpassed in May (2.56σ) and June (4.81σ) 2023. Twelve of sixteen districts surpassed epidemic thresholds during May-June. Investigation revealed inconsistent RDT distribution to facilities over time. National RDT distribution spiked in May 2023, when 551,888 RDT test kits were delivered. This was substantially larger than the 2019-2022 mean for May (53,121, 1,000% increase) and all months (126,866, 435% increase). Subsequently in June 2023, 386,343 tests were performed, 36% higher than the June 2018-2022 mean (285,123). Staff at all four visited facilities reported recurrent RDT stockouts. The proportion of facilities in Sierra Leone reporting positive RDT stocks at both the start and end of the month increased from 14% in April to 74% in June. 51% of facilities began May with RDT stockout and received RDTs that month. CONCLUSIONS: The 2023 spike in confirmed malaria was likely related to increased testing following an unusually large distribution of RDTs. Fluctuations in RDT availability impede the ability to recognize true case variations. Sierra Leone and its partners can strengthen supply chain logistics and health commodity stock tracking to ensure a consistent supply of RDTs and improve interpretation of surveillance data.

OBJECTIVE: We investigated associations between per- and polyfluoroalkyl substances (PFAS) and changes in diabetes indicators from pregnancy to 12 years after delivery among women with a history of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: Eighty Hispanic women with GDM history were followed from the third trimester of pregnancy to 12 years after delivery. Oral and intravenous glucose tolerance tests were conducted during follow-up. Plasma PFAS concentrations were measured at the third trimester of pregnancy and first postpartum visit. A linear mixed-effects model was used to analyze associations between PFAS and trajectories of diabetes indicators, adjusted for age, breastfeeding status, daily total calorie intake, and body fat percentage. RESULTS: Increased 2-(N-methyl-perfluorooctane sulfonamido) acetate level was associated with faster increase in concentrations of fasting glucose (P = 0.003). Increased perfluorononanoate (PFNA) and linear perfluorooctanoate (n-PFOA) concentrations were associated with faster increase in fasting insulin concentrations (P = 0.04 for PFNA; P = 0.02 for n-PFOA) and faster decrease in acute insulin response to glucose (P = 0.04 for PFNA; P = 0.02 for n-PFOA). CONCLUSIONS: PFAS exposure is associated with glucose intolerance, insulin resistance, and β-cell dysfunction, thus increasing type 2 diabetes risk.

BACKGROUND: Evaluation of optimal dosing has generally been inadequate during TB drug development. Fluoroquinolones are central to TB treatment. We aimed to determine the dose of levofloxacin needed to achieve maximal efficacy and acceptable safety and tolerability as part of a multidrug TB regimen. METHODS: Opti-Q was an international, multi-center, randomized, placebo-controlled, phase II trial. Eligible participants with TB resistant to isoniazid and rifampicin but susceptible to fluoroquinolones (MDR-TB) were randomized to receive one of four weight-adjusted once-daily doses of levofloxacin given for 24 weeks(168 doses): 11mg/kg(750mg), 14mg/kg(750mg/1000mg), 17 mg/kg(1000mg/1250mg) or 20mg/kg(1250mg/1500mg) alongside a multidrug regimen. The primary efficacy outcome was time to sputum culture conversion and the primary safety outcome was grade 3 or higher adverse events. FINDINGS: 111 participants were randomized from three sites in South Africa and Peru. 83(75%) had cavities on chest x-ray, 55(50%) had a smear grading of 3+, median BMI was 20.4 kg/m(2). Median levofloxacin AUC/MIC was 573, 633, 918 and 1343 across the four treatment arms. There was no difference in time to culture conversion on solid or liquid media by treatment arm (stratified log-rank p=0.282), by tertile of AUC/MIC (p=0.350), or by dose received (p=0.723); 69.3%, 74.8%, 70.6% and 78.3% achieved culture conversion after 8 weeks on solid media respectively across the treatment arms; 64.6%, 69.5%, 52.6% and 69.6% in liquid culture. More participants experienced a grade 3-5 adverse event by dose (37.0% and 16.0% in the highest and lowest dose groups respectively, p=0.042, Cochran-Armitage test for trend) and by tertile of AUC (p=0.011). INTERPRETATION: As part of a multidrug regimen, doses of levofloxacin above 1000mg resulted in greater exposures and increased frequency of adverse events but did not result in faster time to sputum culture conversion. A dose of 1000mg daily can achieve the target exposure in nearly all adults and was well tolerated. Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT01918397.

BACKGROUND: Lipoprotein(a) [Lp(a)] is an independent risk factor for cardiovascular diseases (CVD). Recent clinical guidelines recommend measuring Lp(a); however, the lack of Lp(a) assay standardization presents challenges to using common clinical decision points. Assay standardization may minimize inter-assay variability. This improves consistency in CVD risk assessment and evaluations of Lp(a) therapeutic efficacy. Genetically determined size variations in the defining apolipoprotein(a) [apo(a)] protein contribute to inter-individual Lp(a) heterogeneity. Individuals who express 2 apo(a) isoforms have 2 sizes of apo(a) in circulation, further contributing to Lp(a) heterogeneity. OBJECTIVE: The Centers for Disease Control and Prevention's Clinical Standardization Programs (CDC CSP) recently launched an Lp(a) standardization program based on the International Federation of Clinical Chemistry endorsed liquid-chromatography mass spectrometry-based reference measurement procedure (RMP). As part of this program, CDC CSP conducted an interlaboratory comparison study to evaluate current Lp(a) inter-assay variability and to investigate potential factors contributing to measurement variability. METHODS: Eight clinical laboratories measured Lp(a) in 40 individual donor serum samples and 3 serum pools. Serum samples were immunophenotyped by Western blot analysis to determine Lp(a) isoform sizes. Sample concentrations were measured in duplicate over 2 independent runs. RESULTS: Assay-specific Lp(a) measurements demonstrated good linear correlation with the RMP. Lp(a) inter-assay measurement variations ranged from 3.3% to 69.1% across individual samples; however, Lp(a) inter-assay coefficients of variation did not increase in a concentration-dependent manner and were not correlated with Lp(a) isoform sizes. CONCLUSION: This study provides new insights into Lp(a) inter-assay variability and assay performance in clinical laboratories that will guide future standardization efforts.

OBJECTIVES: Direct electronic access to multiple electronic health record (EHR) systems through patient portals offers a novel avenue for decentralized research. Given the critical value of patient characterization, we sought to compare computable evaluation of health conditions from patient-portal EHR against the traditional self-report. MATERIALS AND METHODS: In the nationwide Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE) study, which linked self-reported questionnaires with multiplatform patient-portal EHR data, we compared self-reported health conditions across different clinical domains against computable definitions based on diagnosis codes, medications, vital signs, and laboratory testing. We assessed their concordance using Cohen's Kappa and the prognostic significance of differentially captured features as predictors of 1-year all-cause hospitalization risk. RESULTS: Among 1683 participants (mean age 41 ± 15 years, 67% female, 63% non-Hispanic Whites), the prevalence of conditions varied substantially between EHR and self-report (-13.2% to +11.6% across definitions). Compared with comprehensive EHR phenotypes, self-report under-captured all conditions, including hypertension (27.9% vs 16.2%), diabetes (10.1% vs 6.2%), and heart disease (8.5% vs 4.3%). However, diagnosis codes alone were insufficient. The risk for 1-year hospitalization was better defined by the same features from patient-portal EHR (area under the receiver operating curve [AUROC] 0.79) than from self-report (AUROC 0.68). DISCUSSION: EHR-derived computable phenotypes identified a higher prevalence of comorbidities than self-report, with prognostic value of additionally identified features. However, definitions based solely on diagnosis codes often undercaptured self-reported conditions, suggesting a role of broader EHR elements. CONCLUSION: In this nationwide study, patient-portal-derived EHR data enabled extensive capture of patient characteristics across multiple EHR platforms, allowing better disease phenotyping compared with self-report.

Candida species are the predominant cause of fungal infections in patients treated in hospital, contributing substantially to morbidity and mortality. Candidaemia and other forms of invasive candidiasis primarily affect patients who are immunocompromised or critically ill. In contrast, mucocutaneous forms of candidiasis, such as oral thrush and vulvovaginal candidiasis, can occur in otherwise healthy individuals. Although mucocutaneous candidiasis is generally not life-threatening, it can cause considerable discomfort, recurrent infections, and complications, particularly in patients with underlying conditions such as diabetes or in those taking immunosuppressive therapies. The rise of difficult-to-treat Candida infections is driven by new host factors and antifungal resistance. Pathogens, such as Candida auris (Candidozyma auris) and fluconazole-resistant Candida parapsilosis, pose serious global health risks. Recent taxonomic revisions have reclassified several Candida spp, potentially causing confusion in clinical practice. Current management guidelines are limited in scope, with poor coverage of emerging pathogens and new treatment options. In this Review, we provide updated recommendations for managing Candida infections, with detailed evidence summaries available in the appendix.

Larval source management (LSM) has a long history of advocacy and successes but is rarely adopted where funds are limited. The World Health Organization (WHO) guidelines on malaria prevention recommend the use of LSM as a supplementary intervention to the core vector control methods (insecticide-treated nets and indoor residual spraying), arguing that its feasibility in many settings can be limited by larval habitats being numerous, transient, and difficult to find or treat. Another key argument is that there is insufficient high-quality evidence for its effectiveness to support wide-scale implementation. However, the stagnation of progress towards malaria elimination demands that we consider additional options to the current emphasis on insecticidal commodities targeting adult mosquitoes inside homes. This letter is the result of a global, crossdisciplinary collaboration comprising: (a) detailed online expert discussions, (b) a narrative review of countries that have eliminated local malaria transmission, and (c) a mathematical modeling exercise using two different approaches. Together, these efforts culminated in seven key recommendations for elevating larval source management as a strategy for controlling malaria and other mosquito-borne diseases in Africa (Box 1). LSM encompasses the use of larvicide (a commodity) as well as various environmental sanitation measures. Together, these efforts lead to the long-term reduction of mosquito populations, which benefits the entire community by controlling both disease vector and nuisance mosquitoes. In this paper, we argue that the heavy reliance on large-scale cluster-randomized controlled trials (CRTs) to generate evidence on epidemiological endpoints restricts the recommendation of approaches to only those interventions that can be measured by functional units and deliver relatively uniform impact and, therefore, are more likely to receive financial support for conducting these trials. The explicit impacts of LSM may be better captured by using alternative evaluation approaches, especially high-quality operational data and a recognition of locally distinct outcomes and tailored strategies. LSM contributions are also evidenced by the widespread use of LSM strategies in nearly all countries that have successfully achieved malaria elimination. Two modelling approaches demonstrate that a multifaceted strategy, which incorporates LSM as a central intervention alongside other vector control methods, can effectively mitigate key biological threats such as insecticide resistance and outdoor biting, leading to substantial reductions in malaria cases in representative African settings. This argument is extended to show that the available evidence is sufficient to establish the link between LSM approaches and reduced disease transmission of mosquito-borne illnesses. What is needed now is a significant boost in the financial resources and public health administration structures necessary to train, employ and deploy local-level workforces tasked with suppressing mosquito populations in scientifically driven and ecologically sensitive ways. In conclusion, having WHO guidelines that recognize LSM as a key intervention to be delivered in multiple contextualized forms would open the door to increased flexibility for funding and aid countries in implementing the strategies that they deem appropriate. Financially supporting the scale-up of LSM with high-quality operations monitoring for vector control in combination with other core tools can facilitate better health. The global health community should reconsider how evidence and funding are used to support LSM initiatives.

Background: The World Health Organization (WHO) has developed guidance for community health workers (CHWs) in identifying sick young infants based on clinical signs. We conducted a prospective, observational cohort study to characterise mortality risk of young infants based on their clinical signs. Methods: We conducted a population-based, prospective observational cohort study at five sites in Bangladesh (Sylhet, November 01, 2011–December 31, 2013), India (Vellore and Odisha, September 01, 2013–February 28, 2015), and Pakistan (Karachi, January 01, 2012–December 31, 2013; Matiari, March 01, 2012–December 31, 2013) to identify newborn infants who were followed-up by CHWs through 10 scheduled home visits over the first 60 completed days after birth to identify signs of possible serious bacterial infection (PSBI). We determined the frequency of signs and conducted Cox regression to investigate the association of signs with mortality risk within 7 days of identification of the signs. Findings: CHWs made 522,309 visits to assess 63,017 young infants and found ≥1 sign(s) of PSBI at 14,245 visits (2.7%), including 5.8% (5568 of 96,390) and 1.8% (6635 of 365,769) of visits of infants 0–<3 and 7–<60 days of age, respectively. Each of the seven signs of PSBI when found alone was associated with significantly (p < 0.0001) increased risk for mortality, which increased further if any other additional sign of PSBI was found concurrently. Over the young infant period (days 0–<60) CHW identification of no movement or movement only on stimulation was associated with the highest risk for mortality [adjusted hazard ratio (aHR) 73.0, 95% confidence interval (CI) 44.4–119.9] followed by poor feeding (aHR 31.9, 95% CI 24.1–42.3) and hypothermia (<35.5 °C) (aHR 31.4, 95% CI 23.5–41.9). Hypothermia had particularly high risk for mortality during days 7–<60 (HR 45.1, 95% CI 27.6–73.4). Interpretation: WHO reconsideration of hypothermia as a sign of critical illness is warranted. Implementation research is urgently needed to reduce infant mortality by ensuring immediate referrals and interventions for children identified early by CHWs with no movement or movement only on stimulation, hypothermia, or poor feeding, especially in resource-poor settings. Funding: Bill and Melinda Gates Foundation, New Venture Fund for Global Policy and Advocacy. © 2025 The Author(s)

IMPORTANCE: Health information technology, such as electronic health records (EHRs), has been widely adopted, yet accessing and exchanging data in the fragmented US health care system remains challenging. To unlock the potential of EHR data to improve patient health, public health, and health care, it is essential to streamline the exchange of health data. As leaders across the US Department of Health and Human Services (DHHS), we describe how DHHS has implemented fundamental building blocks to achieve this vision. OBSERVATIONS: Across DHHS, we have implemented 3 foundational building blocks called for by the 2016 21st Century Cures Act to create a unified approach for secure, high-quality, and timely exchange of health data across the health care system. The United States Core Data for Interoperability provides a minimum baseline for data elements that must be available in federally regulated health information technology systems such as certified EHRs. These data elements now must be accessible using Fast Healthcare Interoperability Resources-a secure, flexible, and open-industry standard for health data exchange. The Trusted Exchange Framework and Common Agreement provides a network to securely exchange health data across the country. The 3 building blocks of United States Core Data for Interoperability, Fast Healthcare Interoperability Resources, and Trusted Exchange Framework and Common Agreement are now in place thanks to diligent public and private sector work over 2 administrations. Across DHHS, we are working to refine these building blocks and increase their adoption through regulatory authorities, grants, and public-private partnerships. CONCLUSIONS AND RELEVANCE: The technological building blocks described in this article are creating a unified approach to health data exchange for patient access, clinical care, quality improvement, scientific research, public health, and other uses of health data. Collaborations between the public, nonprofit, and private sectors are needed to maximize their potential. By unlocking the potential of health data, these building blocks are the foundation of a 21st-century digital health care system that will improve the experience of patients and clinicians and result in better health outcomes.

OBJECTIVES: On July 28, 2022, eastern Kentucky experienced the state's deadliest flood in recorded history. In response to ongoing mental health concerns from community members who survived the flood, local health department directors in affected communities requested technical assistance from the Kentucky Department for Public Health and the Centers for Disease Control and Prevention. METHODS: Two simultaneous Community Assessments for Public Health Emergency Response (CASPERs) were conducted 6 weeks after the flood. Four counties were assessed in each CASPER. EpiInfo7 was used to calculate the unweighted and weighted frequencies and percentages to estimate the number and percentage of households with a particular response in each CASPER. RESULTS: Approximately a third (30.5%) of households in CASPER 1 and approximately 40% of households in CASPER 2 reported experiencing ≥1 mental health problems. Individual-level mental health questions from a modified 3-stage CASPER found approximately 15% of persons in both CASPERs reported a Patient Health Questionnaire-2 (PHQ-2) score ≥3 and approximately 20% of persons in both CASPERs reported Generalized Anxiety Disorder-2 (GAD-2) score ≥3. CONCLUSIONS: These findings indicated households experienced mental health problems after the flood. Depression and anxiety were prevalent among persons living in flood-affected areas. If ever needed, households preferred to receive mental health services in-person and locally.

BACKGROUND: Long-acting injectable antiretrovirals (LAI-ARVs) for HIV prevention and treatment have been demonstrated in clinical trials to be non-inferior to daily oral medications, providing an additional option to help users overcome the challenges of daily adherence. Approval and implementation of these regimens in low- and middle-income settings have been limited. METHOD: This study describes the anticipated barriers and facilitators to implementing LAI-ARVs in Vietnam to inform future roll-out. From July to August 2022, we conducted 27 in-depth interviews with healthcare workers and public health stakeholders involved in HIV programs at national, provincial, and clinic levels across four provinces in Vietnam. The interviews followed a semi-structured questionnaire and were audio recorded. Data were analyzed using a rapid thematic analysis approach to identify facilitators and barriers to the adoption of LAI-ARVs. RESULTS: In total, 27 participants from 4 provinces were interviewed including 14 (52%) men and 13 (48%) women. Participants median age was 48 years and they had 11.5 years of experience with HIV services and programs. Perceived user-level facilitators included the greater convenience of injectables in comparison to oral regimens, while barriers included the increased frequency of visits, fear of pain and side effects, and cost. Clinic-level facilitators included existing technical capacity to administer injections and physical storage availability in district health centers, while barriers included lack of space and equipment for administering injections for HIV-related services, concerns about cold chain maintenance for LAI-ART, and workload for healthcare workers. Health system-level facilitators included existing mechanisms for medication distribution, while barriers included regulatory approval processes and concerns about supply chain continuity. CONCLUSION: Overall, participants were optimistic about the potential impact of LAI-ARVs but highlighted important considerations at multiple levels needed to ensure successful implementation in Vietnam. CLINICAL TRIAL NUMBER: Not applicable.

INTRODUCTION: Childhood mental, behavioral, and developmental disorders (MBDD) are common and are associated with poor health and well-being. Monitoring the prevalence of MBDDs among children and factors that may influence health outcomes is important to understanding risk and promoting population health. METHOD: We examined trends in parent-reported lifetime MBDDs among children and associated health promotion and risk indicators from 2016 through 2021 by using data from the National Survey of Children's Health. Estimates of prevalence and average annual percentage change were stratified by specific MBDDs and demographic characteristics (eg, sex, age, race and ethnicity). Children with any MBDDs versus none were compared overall and by MBDD subgroup on health care, family, and community indicators. RESULTS: From 2016 through 2021, MBDD prevalence among children aged 3 to 17 years increased from 25.3% to 27.7%; increases were specific to anxiety, depression, learning disability, developmental delay, and speech or language disorder. Unmet health care needs increased annually by an average of approximately 5% among children with MBDDs. Each year from 2016 to 2021, approximately 60% of children with MBDDs received mental or developmental services in the past 12 months. Each year, a higher percentage of parents of children with MBDDs compared with children without MBDDs reported poor mental health (14.7% MBDD, 5.7% no MBDD) and economic stress (21.6% MBDD, 11.5% no MBDD). CONCLUSION: Increasing prevalence of certain MBDDs and MBDD-associated indicators, before and during the COVID-19 pandemic, highlights the need for improved pediatric mental health training for health care providers, for prevention and intervention efforts, and for policies addressing economic stability and equitable access to mental health services.

BACKGROUND: On July 28, 2022, floods in eastern Kentucky displaced over 600 individuals. With the goal of understanding mental health needs of affected families, we surveyed households living in flood evacuation shelters after the 2022 Kentucky floods. METHODS: Families experiencing displacement from the 2022 Kentucky floods currently living in three different temporary shelter locations were surveyed via convenience sampling. A rapid community needs assessment involving in-person interviews using modified two stage cluster methodology (CASPER) was conducted between September 6-9, 2022. RESULTS: Teams conducted 61 household interviews. Since the flood, 27.7% reported that their household received services from behavioral health and 19.6% received grief counseling. Experiencing agitation (36.7%), difficulty concentrating (47.5%), nightmares (62.3%), or suicidal thoughts/self-harm (6.6%) were reported by households surveyed. Over one-fourth (27.0%) of individuals surveyed reported being depressed nearly every day. Over 20% reported anhedonia (inability to feel pleasure) nearly every day. Over 75% of individuals surveyed reported being anxious several days or more over the last two weeks. Over one-third of individuals (34.0%) reported being unable to stop worrying nearly every day. Of those individuals surveyed, 36.1% reported barriers to mental health services. CONCLUSIONS: Symptoms of depressed mood, anhedonia, anxiety, and nightmares were prevalent in displaced families six weeks after the 2022 Kentucky floods. Providing and encouraging access to mental health services are important priorities during disaster recovery.

OBJECTIVE: To investigate COVID-19 disparities between Hispanic/Latino persons (H/L) and non-H/L persons in an agricultural community by examining behavioral and demographic differences. METHODS: In September 2020, we conducted Community Assessments for Public Health Emergency Response in Wenatchee and East Wenatchee, Washington, to evaluate differences between H/L and non-H/L populations in COVID-19 risk beliefs, prevention practices, household needs, and vaccine acceptability. We produced weighted sample frequencies. RESULTS: More households from predominately H/L census blocks (H/L-CBHs) versus households from predominately non-H/L census blocks (non-H/L-CBHs) worked in essential services (79% versus 57%), could not telework (70% versus 46%), and reported more COVID-19 cases (19% versus 4%). More H/L-CBHs versus non-H/L-CBHs practiced prevention strategies: avoiding gatherings (81% versus 61%), avoiding visiting friends/family (73% versus 36%), and less restaurant dining (indoor 24% versus 39%). More H/L-CBHs versus non-H/L-CBHs needed housing (16% versus 4%) and food assistance (19% versus 6%). COVID-19 vaccine acceptance in H/L-CBHs and non-H/L-CBHs was 42% versus 46%, respectively. CONCLUSIONS: Despite practicing prevention measures with greater frequency, H/L-CBHs had more COVID-19 cases. H/L-CBHs worked in conditions with a higher likelihood of exposure. H/L-CBHs had increased housing and food assistance needs due to the pandemic. COVID-19 vaccine acceptability was similarly low (<50%) between groups.

Medically important pathogenic fungi invade vertebrate tissue and are considered primary when part of their nature life cycle is associated with an animal host and are usually able to infect immunocompetent hosts. Opportunistic fungal pathogens complete their life cycle in environmental habitats or occur as commensals within or on the vertebrate body, but under certain conditions can thrive upon infecting humans. The extent of host damage in opportunistic infections largely depends on the portal and modality of entry as well as on the host's immune and metabolic status. Diseases caused by primary pathogens and common opportunists, causing the top approximately 80% of fungal diseases [D. W. Denning, Lancet Infect Dis, 24:e428-e438, 2024, https://doi.org/10.1016/S1473-3099(23)00692-8], tend to follow a predictive pattern, while those by occasional opportunists are more variable. For this reason, it is recommended that diseases caused by primary pathogens and the common opportunists are named after the etiologic agent, for example, histoplasmosis and aspergillosis, while this should not be done for occasional opportunists that should be named as [causative fungus] [clinical syndrome], for example, Alternaria alternata cutaneous infection. The addition of a descriptor that identifies the location or clinical type of infection is required, as the general name alone may cover widely different clinical syndromes, for example, "rhinocerebral mucormycosis." A list of major recommended human and animal disease entities (nomenclature) is provided in alignment with their causative agents. Fungal disease names may encompass several genera of etiologic agents, consequently being less susceptible to taxonomic changes of the causative species, for example, mucormycosis covers numerous mucormycetous molds.

The Phase 3 randomized controlled trial, TBTC Study 31/ACTG A5349 (NCT02410772) demonstrated that a 4-month rifapentine-moxifloxacin regimen for drug-susceptible pulmonary tuberculosis was safe and effective. The primary efficacy outcome was 12-month tuberculosis disease free survival, while the primary safety outcome was the proportion of grade 3 or higher adverse events during the treatment period. We conducted an analysis of demographic, clinical, microbiologic, radiographic, and pharmacokinetic data and identified risk factors for unfavorable outcomes and adverse events. Among participants receiving the rifapentine-moxifloxacin regimen, low rifapentine exposure is the strongest driver of tuberculosis-related unfavorable outcomes (HR 0.65 for every 100 µg∙h/mL increase, 95%CI 0.54-0.77). The only other risk factors identified are markers of higher baseline disease severity, namely Xpert MTB/RIF cycle threshold and extent of disease on baseline chest radiography (Xpert: HR 1.43 for every 3-cycle-threshold decrease, 95%CI 1.07-1.91; extensive disease: HR 2.02, 95%CI 1.07-3.82). From these risk factors, we developed a simple risk stratification to classify disease phenotypes as easier-, moderately-harder, or harder-to-treat TB. Notably, high rifapentine exposures are not associated with any predefined adverse safety outcomes. Our results suggest that the easier-to-treat subgroup may be eligible for further treatment shortening while the harder-to-treat subgroup may need higher doses or longer treatment.

We reviewed the available evidence on psychosocial treatments for disruptive behaviors in children, as an update to Kaminski and Claussen (2017), focusing on children up to age 12 years. Search strategies, study inclusion, and treatment classification followed the procedures developed by Southam-Gerow and Prinstein (2014). Of the 44 included studies from 2016 to 2021, only 9 impacted previous results, either by increasing the level of evidence (for two treatment families) or documenting evidence for a new treatment family (four new treatment families). All three treatment families classified as Level 1: Well Established are parent-focused and now include Group parent behavior therapy + group child behavior therapy (previously classified as Probably Efficacious), in addition to Group parent behavior therapy and Individual parent behavior therapy with child participation (already classified as Well Established). Fifteen treatment families were classified as Level 2: Probably Efficacious, eight were classified as Level 3: Possibly Efficacious. Given the variability of programs in each treatment family, the evidence is for the overall treatment approach and may not apply to each program with those characteristics. Data were insufficient to examine outcomes in relation to participant characteristics. The information can be used to improve dissemination, implementation, and uptake of effective treatment, and inform research on improving access barriers.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that develops during childhood and can last into adulthood. Data from the National Center for Health Statistics Rapid Surveys System collected during October-November 2023 were used to estimate the prevalence of ADHD diagnosis and treatment among U.S. adults. In 2023, an estimated 15.5 million U.S. adults (6.0%) had a current ADHD diagnosis based on self-report; approximately one half received the diagnosis at age ≥18 years. Approximately one third of adults with ADHD took a stimulant medication to treat their ADHD in the previous year, 71.5% of whom had difficulty getting their ADHD prescription filled because it was unavailable. Approximately one half of adults with ADHD have ever used telehealth for ADHD-related services. Telehealth might have benefits for persons with ADHD, including helping them access behavioral treatment or medication prescriptions for ADHD. This report provides national estimates of the prevalence and treatment of ADHD among U.S. adults to help guide clinical care and regulatory decision-making for ADHD among U.S. adults.