We updated a descriptive analysis of national outpatient antibiotic prescribing during the COVID-19 pandemic. Prescribing volume was lower during 2020 and January-June in 2021 and 2022 compared to corresponding baseline months in 2019. Prescribing approached or exceeded baseline during July-December of 2021 and 2022 for all antibiotics, especially for azithromycin.

BACKGROUND: The objective of this study was to identify antibiotic stewardship (AS) opportunities in Latin American medical-surgical intensive care units (MS-ICUs) and general wards (Gral-wards). METHODS: We conducted serial cross-sectional point prevalence surveys in MS-ICUs and Gral-wards in 41 Latin American hospitals between March 2022 and February 2023. Patients >18 years of age in the units of interest were evaluated for antimicrobial use (AU) monthly (MS-ICUs) or quarterly (Gral-wards). Antimicrobial data were collected using a standardized form by the local AS teams and submitted to the coordinating team for analysis. RESULTS: We evaluated AU in 5780 MS-ICU and 7726 Gral-ward patients. The hospitals' median bed size (interquartile range) was 179 (125-330), and 52% were nonprofit. The aggregate AU prevalence was 53.5% in MS-ICUs and 25.5% in Gral-wards. Most (88%) antimicrobials were prescribed to treat infections, 7% for surgical prophylaxis and 5% for medical prophylaxis. Health care-associated infections led to 63% of MS-ICU and 38% of Gral-ward AU. Carbapenems, piperacillin-tazobactam, intravenous (IV) vancomycin, and ampicillin-sulbactam represented 50% of all AU to treat infections. A minority of IV vancomycin targeted therapy was associated with documented methicillin-resistant Staphylococcus aureus infection or therapeutic drug monitoring. In both units, 17% of antibiotics prescribed as targeted therapy represented de-escalation, while 24% and 15% in MS-ICUs and Gral-wards, respectively, represented an escalation of therapy. In Gral-wards, 32% of antibiotics were used without a microbiologic culture ordered. Half of surgical prophylaxis antibiotics were prescribed after the first 24 hours. CONCLUSIONS: Based on this cohort, areas to improve AU in Latin American hospitals include antibiotic selection, de-escalation, duration of therapy, and dosing strategies.

AIM: Among people with diabetes those with chronic kidney disease (CKD) have a reduced life expectancy with increased risk of cardiovascular disease (CVD) a major contributor to morbidity and mortality. CKD related to diabetes is growing worldwide and is one of the leading causes of kidney failure globally. Diabetes is associated with accelerated vascular ageing and the related mechanisms and mediators that drive the progression of CKD and CVD disease in people with diabetes may help provide insights into the pathophysiology of cardio-renal complications and guide treatment interventions in people with diabetes. METHODS: We conducted a narrative review of the literature using PubMed for English language articles that contained keywords that related to diabetes, chronic or diabetic kidney disease, ageing, cellular senescence, arterial stiffness, Klotho and sirtuins, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, renin angiotensin aldosterone system (RAAS) and glucagon-like peptide-1 (GLP-1) receptor agonists. RESULTS: Progressive kidney disease in diabetes is associated with accelerated ageing driven in part by multiple processes such as cellular senescence, inflammation, oxidative stress and circulating uremic toxins. This accelerated ageing phenotype contributes to increased arterial stiffness, endothelial dysfunction, cognitive decline and muscle wasting, thereby elevating morbidity and mortality in individuals with diabetes and CKD. Deficiency of the kidney-derived anti-ageing hormone Klotho and reduced sirtuin levels play pivotal roles in these ageing pathways. Dietary, lifestyle and pharmacological interventions targeting vascular ageing may help reduce the progression of CKD and associated CVD in people with diabetes. The current standard of care and pillars of treatment for kidney disease such as RAAS inhibitors, SGLT-2 inhibitors and GLP-1 receptor agonists all influence pathways involved in vascular ageing. CONCLUSIONS: A multifactorial intervention to prevent the development of CKD by targeting traditional risk factors as well as treatment with novel agents with cardio-renal beneficial effects can prevent accelerated ageing and extend lifespan in people with diabetes.

BACKGROUND: Myotonic dystrophy type 1 (DM1) is a multisystem genetic disorder that classically presents with symptoms associated with myotonia, early onset cataracts, and muscular weakness, although the presentation and pattern of disease progression is quite varied. Presenting symptoms are well documented among adults with DM1. However, less is known about the co-occurrence of symptoms over time. We aimed to use factor analysis to explore the correlation pattern of signs and symptoms (S/S) that emerged during the clinical course. RESULTS: Clinical records of 228 individuals with adult onset DM1 were abstracted using the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) from a six-site cohort in the United States during an eight-year study period. Factor analysis was used to group the correlated S/S into latent factors. Three factors were identified. Group 1: 'Facial Weakness/Myotonia' includes the two most common S/S, as indicated by its name. Group 2: 'Skeletal Muscle Weakness' includes eight muscular S/S and is more frequently reported by males and those with older age at onset. Group 3: 'Gastrointestinal distress/Sleepiness' includes four non-muscular S/S and hand stiffness. The abstracted medical records reported that over 63% of individuals had S/S from all three groups. Associations of covariates with factor scores were also examined using linear regression. CTG repeat length was significantly positively associated with higher factor scores for all three factors. CONCLUSIONS: This study identified three latent factors of S/S which accumulated during the clinical course of adult onset DM1.

BACKGROUND: Acute gastroenteritis (AGE) is a major medical condition for travellers worldwide, particularly travellers to low- and middle-income countries. Norovirus (NoV) is the most common cause of viral AGE in older children and adults, but data on prevalence and impact amongst travellers is limited. METHODS: Prospective, multi-site, observational cohort study conducted 2015-2017, amongst adult international travellers from the US and Europe to areas of moderate to high risk of travel-acquired AGE. Participants provided self-collected pre-travel stool samples and self-reported AGE symptoms whilst travelling. Post-travel stool samples were requested from symptomatic subjects and a sample of asymptomatic travellers within 14 days of return. Samples were tested for NoV by RT-qPCR, genotyped if positive and tested for other common enteric pathogens by Luminex xTAG GPP. RESULTS: Of the 1109 participants included, 437 (39.4%) developed AGE symptoms resulting in an overall AGE incidence of 24.7 per 100 person-weeks [95% confidence interval (CI): 22.4; 27.1]. In total, 20 NoV-positive AGE cases (5.2% of those tested) were identified at an incidence of 1.1 per 100 person-weeks (95% CI: 0.7; 1.7). NoV-positive samples belonged mostly to genogroup GII (18, 85.7%); None of the 13 samples sequenced belonged to genotype GII.4. Clinical severity of AGE was higher for NoV-positive than for NoV-negative cases (mean modified Vesikari Score 6.8 vs 4.9) with more cases classified as severe or moderate (25% vs 6.8%). In total, 80% of NoV-positive participants (vs 38.9% in NoV-negative) reported at least moderate impact on travel plans. CONCLUSIONS: AGE is a prevalent disease amongst travellers with a small proportion associated with NoV. Post-travel stool sample collection timing might have influenced the low number of NoV cases detected; however, NoV infections resulted in high clinical severity and impact on travel plans. These results may contribute to targeted vaccine development and the design of future studies on NoV epidemiology.

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.

Lassa fever is a serious epidemic viral disease in West Africa affecting an estimated 2 million people annually with about 5000-10,000 deaths, although supporting data is sparse. Lassa fever significantly affects neonates, children, and pregnant women, however, comprehensive data on its impact in these populations are lacking. We reviewed the available literature on Lassa fever to assess its prevalence and impact in these populations and implications for vaccine development. Clinical features in children were similar to those observed in adults, with complications such as bleeding. Altered mental status, anasarca (swollen baby syndrome), bleeding, and poor urine output were risk factors for death. The case fatality rate (CFR) in 16 paediatric studies ranged from 6 % to 63 % and was 66.7 % and 75.0 % in two neonatal studies. In a systematic review of studies on pregnant women the CFR was 33.73 %. The adverse foetal outcomes included miscarriage, stillbirth, and intrauterine death associated with maternal death. Since Lassa fever significantly affects neonates, children, and pregnant women, developing a safe and effective, single-dose vaccine for these high-risk populations is vital. Currently, there are four clinical trials assessing Lassa virus vaccines. Only one of these trials is enrolling children aged ≥18 months, and exclude pregnant and breast-feeding women. It is essential that pregnant and breast-feeding women and young children are included in clinical trials that incorporate robust safety surveillance and risk mitigation measures. In our review, potential approaches to address the specific gaps in the areas of diagnosis, management, and prevention of Lassa fever in these specific populations, such as disease surveillance systems and vaccine development, were identified. A comprehensive strategy with investment focused on addressing specific knowledge gaps will be essential in protecting the health of these specific populations in Lassa virus endemic regions.

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

Invasive meningococcal disease (IMD) is a severe illness that can have devastating effects; outbreaks are uncommon in the United States. Vaccination is the preferred control measure for IMD outbreaks when a defined population at risk (e.g., college students or persons experiencing homelessness) can be identified. In August 2022, the Virginia Department of Health (VDH) began investigating an IMD outbreak in Virginia's Eastern Health Planning Region, prompted by the detection of four confirmed cases within 8 weeks. Clinical isolates available from three cases were characterized as Neisseria meningitidis serogroup Y, sequence type 1466. A subsequent statewide investigation identified 36 genetically related cases, including seven deaths (case fatality rate = 19.4%) as of March 1, 2024. A majority of patients (63.9%) were in an age group (30-60 years) not generally considered at increased risk for IMD; 78.0% were non-Hispanic Black or African American. No common exposures, affiliations, or risk factors were identified, and a defined population could not be identified for vaccination. VDH recommended quadrivalent (serogroups A, C, W, and Y) meningococcal conjugate vaccination of a subset of close contacts of patients based on IMD risk factors and age range similar to that of patients with identified cases. IMD outbreaks might affect populations without established IMD risk factors. Lack of a well-defined population at risk might prompt exploration of novel control strategies, such as selective vaccination of close contacts.

BACKGROUND: Household transmission of SARS-CoV-2 is a driver of the ongoing COVID-19 pandemic. Understanding factors that contribute to secondary infection risks (SIRs) can define changing trends and inform public health policies. METHODS: The ORegon CHild Absenteeism due to Respiratory Disease Study (ORCHARDS) prospectively monitors respiratory viruses within the Oregon School District (OSD) in southcentral Wisconsin. Households with students who had ≥ 2 respiratory symptoms were eligible and opted to participate in ORCHARDS. Between October 28, 2020, and May 16, 2022, all household members provided self-collected nasal specimens on days 0, 7, and 14 for SARS-CoV-2 detection using real-time reverse-transcription-polymerase chain reaction. We used logistic regression to investigate individual- and household-level characteristics associated with SARS-CoV-2 transmission. RESULTS: Overall, 127 households comprising 572 individuals (48% female; 52% male; 0.4% nonbinary; 77% ≥ 18 years) had at least one detection of SARS-CoV-2. The overall SIR was 47% and decreased over time (pre-Delta = 72% [95% CI: 58%-83%]; Delta = 51% [40%-63%]; and Omicron = 41% [36%-47%]). Odds of household transmission were 63% lower during the Omicron period compared with the pre-Delta period (OR = 0.36 [95% CI: 0.13-0.94] p = 0.037). Greater household density (members/bedroom) was significantly associated with household transmission during the Omicron period (OR = 6.8, [2.19-21.37] p = 0.001). Index case age, illness severity, and individual symptoms were not significantly associated with odds of household transmission. CONCLUSIONS: Greater household density was associated with a higher risk of SARS-CoV-2 transmission, but the risk declined over time with subsequent variants. Interplay between variants, prior infection, and individual/household factors may identify modifiable factors (e.g., behavior and vaccination) to reduce future transmission risk.

This article reports changes to virus taxonomy and taxon nomenclature that were approved and ratified by the International Committee on Taxonomy of Viruses (ICTV) in April 2024. The entire ICTV membership was invited to vote on 203 taxonomic proposals that had been approved by the ICTV Executive Committee (EC) in July 2023 at the 55th EC meeting in Jena, Germany, or in the second EC vote in November 2023. All proposals were ratified by online vote. Taxonomic additions include one new phylum (Ambiviricota), one new class, nine new orders, three new suborders, 51 new families, 18 new subfamilies, 820 new genera, and 3547 new species (excluding taxa that have been abolished). Proposals to complete the process of species name replacement to the binomial (genus + species epithet) format were ratified. Currently, a total of 14,690 virus species have been established.

A better understanding of viral factors that contribute to influenza A virus (IAV) airborne transmission is crucial for pandemic preparedness. A limited capacity for airborne transmission was recently observed in a human A(H9N2) virus isolate (A/Anhui-Lujiang/39/2018, AL/39) that possesses a leucine (L) residue at position HA1-226 (H3 numbering), indicative of human-like receptor binding potential. To evaluate the roles of the residue at this position in virus fitness and airborne transmission, a wild-type AL/39 (AL/39-wt) and a mutant virus (AL/39-HA1-L226Q) with a single substitution at position HA1-226 from leucine to glutamine (Q), a consensus residue in avian influenza viruses, were rescued and assessed in the ferret model. The AL/39-HA1-L226Q virus lost the ability to transmit by air, although the virus had a comparable capacity for replication, induced similar levels of host innate immune responses, and was detected at comparable levels in the air surrounding the inoculated ferrets relative to AL/39-wt virus. However, ferrets showed a lower susceptibility to AL/39-HA1-L226Q virus infection compared to the AL/39-wt virus. Furthermore, the AL/39-wt and AL/39-HA1-L226Q viruses each gained dominance in different anatomic sites in the respiratory tract in a co-infection competition model in ferrets. Taken together, our findings demonstrate that the increasing dominance of HA1-L226 residue in an avian A(H9N2) virus plays multifaceted roles in virus infection and transmission in the ferret model, including improved virus fitness and infectivity. IMPORTANCE: Although the capacity for human-like receptor binding is a key prerequisite for non-human origin influenza A virus (IAV) to become airborne transmissible in mammalian hosts, the underlying molecular basis is not well understood. In this study, we investigated a naturally occurring substitution (leucine to glutamine) at residue 226 in the HA of an avian-origin A(H9N2) virus and assessed the impact on virus replication and airborne transmission in the ferret model. We demonstrate that the enhanced airborne transmission associated with the HA1-L226 virus was mainly due to the increased infectivity of the virus. Interestingly, we found that, unlike most sites in the ferret respiratory tract, ferret ethmoid turbinate lined with olfactory epithelium favors replication of the AL/39-HA1-L226Q virus, suggesting that this site may serve as a unique niche for IAV with avian-like receptor binding specificity to potentially allow the virus to spread to extrapulmonary tissues and to facilitate adaptation of the virus to human hosts.

BACKGROUND: Recovery from SARS CoV-2 infection is expected within 3 months. Long COVID occurs after SARS-CoV-2 when symptoms are present for more than 3 months that are continuous, relapsing and remitting, or progressive. Better understanding of Long COVID illness trajectories could strengthen patient care and support. METHODS: We characterized functional impairments, quality of life (QoL), and cognition among patients who recovered from SARS-CoV-2 infection within 3 months (without Long COVID), after 3 months (Recovered Long COVID), or remained symptomatic (Long COVID). Among 7305 patients identified with previous SARS-CoV-2 infection between March 2020 and December 2021, confirmed in the medical record with laboratory test or physician diagnosis, 435 (6%) completed a single self-administered survey between March 2022 and September 2022. Multi-domain QoL and cognitive concerns were evaluated using PROMIS-29 and the Cognitive Change Index-12. RESULTS: Nearly half the participants (47.7%) were surveyed more than 2 years from initial infection (median = 23.3 months; IQR = 18.6, 26.7) and 86.7% were surveyed more than 1 year from infection. A significantly greater proportion of the Long COVID (n = 215) group, (Current and Recovered combined), had moderate-to-severe impairment in all health domains assessed compared to those Without Long COVID (n = 220; all p < 0.05). The Recovered Long COVID group (n = 34) had significantly lower prevalence of fatigue, pain, depression, and physical and social function impairment compared to those with Current Long COVID (n = 181; all p < 0.05). However, compared to patients Without Long COVID, the Recovered Long COVID group had greater prevalences of fatigue, pain (p ≤ 0.06) and subjective cognitive decline (61.8% vs 29.1%; p < 0.01). Multivariate relative risk (RR) regression indicated Long COVID risk was greater for older age groups (RR range 1.46-1.52; all p ≤ 0.05), those without a bachelor's degree (RR = 1.33; 95% CI = 1.03-1.71; p = 0.03), and those with 3 or more comorbidities prior to SARS-CoV-2 infection (RR = 1.45; 95% CI = 1.11-1.90; p < 0.01). CONCLUSIONS: Long COVID is associated with long-term subjective cognitive decline and diminished quality of life. Clinically significant cognitive complaints, fatigue, and pain were present even in those who reported they had recovered from Long COVID. These findings have implications for the sustainability of participation in work, education, and social activities.

BACKGROUND: Screening for SARS-CoV-2 infection among hospital admissions made interpretation of COVID-19 hospitalization data challenging as SARS-CoV-2-positive persons with mild or asymptomatic infection may be incorrectly identified as COVID-19-associated hospitalizations. The study objective is to estimate the proportion of hospitalizations likely attributable to COVID-19 among SARS-CoV-2-positive hospitalized patients. METHODS: A sample of laboratory-confirmed SARS-CoV-2-positive hospitalizations from the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) from June 2020 to September 2023 was analyzed, with a focus on July 2022 to September 2023. Likely COVID-19-attributable hospitalizations were defined as hospitalizations among SARS-CoV-2-positive non-pregnant adults ages ≥ 18 years with COVID-19-related presenting complaint, treatment, or discharge diagnosis. RESULTS: Among 44,816 sampled hospitalizations, 90% met the definition of likely COVID-19-attributable. Among the 9866 admissions occurring during July 2022 to September 2023, 86% were likely COVID-19-attributable; 87% had a COVID-19-related presenting complaint, 64% received steroids or COVID-19-related treatment, 47% had respiratory- and 10% had coagulopathy-related discharge diagnoses, and 39% had COVID-19 as the principal discharge diagnosis code. More than 70% met ≥ 2 criteria. Compared with likely COVID-19-attributable hospitalizations, SARS-CoV-2-positive patients who did not meet the case definition were more likely to be ages 18-49 years (27% vs. 13%), have no underlying medical conditions (14% vs. 4%), or be asymptomatic for COVID-19 upon admission (46% vs. 10%) (all p < 0.05). CONCLUSIONS: Most hospitalizations among SARS-CoV-2-positive adults in a recent period were likely attributable to COVID-19. COVID-19-attributable hospitalizations are less common among younger SARS-CoV-2-positive hospitalized adults but still account for nearly three quarters of all admissions among SARS-CoV-2-positive adults in this age group.

The World Trade Center (WTC) Health Program is a limited federal health care program that provides medical monitoring and treatment for WTC-related health conditions to responders and survivors impacted by the terrorist attacks on September 11, 2001.This study described the characteristics of the Program survivor members (who lived, worked, went to school, daycare or adult daycare or present in the New York City Disaster Area of 9/11/2001) to stimulate innovative ideas for improving healthcare services, generate new research interest, and serve as a reference for future research on this population. Administrative and medical claims data collected from the Program start date (07/01/2011) through 2022 were used. As of 12/31/2022, there were 37,384 enrolled survivors: 5.0% were aged ≤21 years on 9/11/2001, 45.9% females, and 31.2% non-Hispanic Whites. A total of 24,148 (64.6%) were certified for at least one WTC-related condition, including neoplasms (36.0%), aerodigestive disorders (35.6%) and mental health conditions (18.6%); 22.9% were certified for more than one category. Certification rates of some WTC-related conditions differed by sex, age and race/ethnicity. WTC survivor population is diverse in sex, age and race/ethnicity, with a high proportion certified for certain WTC-related health conditions, providing great opportunities for research in various areas.

There is limited research on associations of per- and polyfluoroalkyl substances (PFAS) with areal bone mineral density (aBMD) through adolescence and whether bone-strengthening factors ameliorate effects. In the Project Viva cohort (N = 484; 50% female), we used sex-stratified linear regression and quantile g-computation mixture models to examine associations of mid-childhood (median: 7.8 years; 2007-2010) plasma PFAS concentrations with a dual-energy X-ray absorptiometry total-body aBMD Z-score in early and late adolescence (median: 12.9 and 17.6 years, respectively). We explored stratum-specific estimates by parent/self-reported physical activity and dairy intake. Using linear mixed models, we evaluated associations with aBMD accrual from mid-childhood through late adolescence. Females with higher perfluorooctanoate (PFOA) and perfluorodecanoate (PFDA) had lower early adolescent aBMD Z-score [e.g., β(95%CI)] per doubling PFOA: -0.19(-0.41, 0.03)]. Youth with higher PFOA and PFDA had lower late adolescent aBMD Z-score, but CIs were wide [e.g., PFOA: females, -0.12(-0.40, 0.16); males, -0.10(-0.42, 0.21)]. Mixture models generally corroborated single PFAS results, and in linear mixed models, females with higher PFAS concentrations, and males with higher PFOA, had slower aBMD accrual. Less active males with higher PFOA, PFDA, and the PFAS mixture had lower late adolescent aBMD Z-score. Some PFAS appeared more negatively associated with the aBMD Z-score among those who consumed less dairy, but there was not consistent evidence of effect modification. Exposure to select PFAS may affect bone accrual through adolescence, with possible resilience conferred by greater physical activity and dairy intake.

BACKGROUND: Environmental chemical exposures in utero may play a role in autism development. While preconception risk factors for autism are increasingly being investigated, little is known about the influence of chemical exposures during the preconception period, particularly for paternal exposures. METHODS: In 195 children from the Preconception Environmental exposures And Childhood health Effects (PEACE) cohort born to parents recruited from a fertility clinic in Boston, Massachusetts between 2004 and 2017, we quantified concentrations of 11 phthalate metabolites and bisphenol A (BPA) in urine samples collected from mothers and fathers before conception and mothers throughout pregnancy. When children were 6-15 years old, parents completed the Social Responsiveness Scale (SRS) questionnaire assessing autistic behaviors. We used linear mixed effect models to estimate covariate-adjusted associations of phthalate biomarker and BPA concentrations, separately for maternal preconception (n = 179), paternal preconception (n = 121), and maternal pregnancy (n = 177), with SRS T-scores, based on age and gender, in offspring. We used quantile g-computation models for mixture analyses and evaluated modification by selected dietary factors. RESULTS: The mean SRS T-score was 47.7 (±7.4), lower than the normative mean of 50. In adjusted models for individual biomarkers or mixtures, few associations were observed and estimates were generally negative (e.g., lower SRS T-scores) and imprecise. We observed associations of higher mono-isobutyl phthalate (MiBP) concentrations measured in maternal preconception and paternal preconception periods with lower SRS T-scores (β(maternal_precon) = -1.6, 95% CI -2.7; -0.4; β(paternal_precon) = -2.9, 95% CI -4.6; -1.2) for each log(e) increase. In a subset of participants with maternal preconception nutrition information, we generally observed stronger inverse associations with higher folate and iron intake, particularly for folate intake and MiBP concentrations. CONCLUSIONS: Urinary phthalate biomarker and BPA concentrations during preconception (maternal and paternal) and pregnancy (maternal) were not associated with adverse autistic behaviors in these children. Larger studies are needed to elucidate the observed associations, while considering interactions between maternal nutrition and chemical exposures.

Epidemiological delays are key quantities that inform public health policy and clinical practice. They are used as inputs for mathematical and statistical models, which in turn can guide control strategies. In recent work, we found that censoring, right truncation, and dynamical bias were rarely addressed correctly when estimating delays and that these biases were large enough to have knock-on impacts across a large number of use cases. Here, we formulate a checklist of best practices for estimating and reporting epidemiological delays. We also provide a flowchart to guide practitioners based on their data. Our examples are focused on the incubation period and serial interval due to their importance in outbreak response and modeling, but our recommendations are applicable to other delays. The recommendations, which are based on the literature and our experience estimating epidemiological delay distributions during outbreak responses, can help improve the robustness and utility of reported estimates and provide guidance for the evaluation of estimates for downstream use in transmission models or other analyses.

BACKGROUND: Mapping health outcomes related to environmental health hazards at the county level can lead to a simplification of risks experienced by populations in that county. The Centers for Disease Control and Prevention's National Environmental Public Health Tracking Program has developed sub-county geographies that aggregate census tracts to allow for stable, minimally suppressed data to be displayed. This helps to highlight more local variation in environmental health outcomes and risk data. However, we wanted to understand whether the aggregation method used was aggregating sociodemographically similar or dissimilar areas with one another. This analysis attempts to explore whether the distributions of select people who may be at increased risk for exposure to environmental health hazards as identified by the Tracking Program are preserved in these sub-county geographies with the census tracts used as the foundation to create them. METHODS: Mean values of three sociodemographic characteristics (persons aged 65 years and older, people from racial and ethnic minority groups, and population below the poverty level) for each sub-county geography in five states were calculated and placed into five break groups. Differences in break groups were determined and compared for each sub-county geography and census tract. RESULTS: The sociodemographic characteristics among the census tracts and two aggregated sub-county geographies were similar. In some instances, census tracts with a low population or a highly skewed population (e.g., very high percentage of population aged 65 years and older) were aggregated with dissimilar census tracts out of necessity to meet the requirements set by the Tracking Program's aggregation methodology. This pattern was detected in 2.41-6.59% of census tracts within the study area, depending on the sociodemographic variable and aggregation level. CONCLUSIONS: The Tracking Program's sub-county aggregation methodology aggregates census tracts with similar characteristics. The two new sub-county geographies can serve as a potential option for health officials and policymakers to develop targeted interventions using finer resolution health outcome and environmental hazard data compared to coarser resolution county-level data.

We investigated a suspected norovirus outbreak associated with a wedding reception in Wisconsin in May 2015. Fifty-six of 106 (53%) wedding attendees were interviewed and 23 (41%) reported symptoms consistent with norovirus infection. A retrospective cohort study identified fruit salad as the likely vehicle of infection (risk ratio 3.2, 95% confidence interval 1.1- 8.3). Norovirus was detected by real-time reverse transcription polymerase chain reaction (RT-qPCR) in stool specimens collected from four attendees and one food handler and in 12 leftover fruit salad samples from both an opened and a sealed container. Norovirus-positive clinical samples (n=4) were genotyped as GII.4 Sydney and norovirus-positive fruit salad samples (n=2) confirmed the presence of GII.4 norovirus by Sanger sequencing with 98% nucleotide (n=236) similarity in 5' end of ORF2 between fruit salad and clinical specimens. In conclusion, this comprehensive norovirus outbreak investigation combined epidemiologic, virologic, and environmental findings to traceback the contaminated food as the source of the outbreak.

BACKGROUND: Hypertension affects nearly half of US adults yet remains inadequately controlled in over three-quarters of these cases. This study aimed to assess the association between adherence to antihypertensive medications and total medical costs, health care use, and productivity-related outcomes. METHODS AND RESULTS: We conducted cross-sectional analyses using MarketScan databases, which included individuals aged 18 to 64 years with noncapitated health insurance plans in 2019. Adherence was defined as ≥80% medication possession ratio for prescribed antihypertensive medications. We used a generalized linear model to estimate total medical costs, a negative binomial model to estimate health care use (emergency department visits and inpatient admissions), an exponential hurdle model to estimate productivity-related outcomes (number of sick absences, short-term disability, long-term disability), and a 2-part model to estimate productivity-related costs in 2019 US dollars. All models were adjusted for age, sex, urbanicity, census region, and comorbidities. We reported average marginal effects for outcomes related to antihypertensive medication adherence. Among 379 503 individuals with hypertension in 2019, 54.4% adhered to antihypertensives. Per person, antihypertensive medication adherence was associated with $1441 lower total medical costs, $11 lower sick absence costs, $291 lower short-term disability costs, and $69 lower long-term disability costs. Per 1000 individuals, medication adherence was associated with lower health care use, including 200 fewer emergency department visits and 90 fewer inpatient admissions, and productivity-related outcomes, including 20 fewer sick absence days and 442 fewer short-term disability days. CONCLUSIONS: Adherence to antihypertensives was consistently associated with lower total medical costs, reduced health care use, and improved productivity-related outcomes.

BACKGROUND: Infection prevention and control (IPC) programs are essential to prevent and control the spread of multidrug-resistant organisms in healthcare facilities (HCFs). The current implementation of these programs in Latin America remains largely unknown. METHODS: We conducted a mixed-methods evaluation of IPC program implementation in HCFs from Guatemala, Panama, Ecuador, and Argentina, March-July 2022. We used the World Health Organization (WHO) IPC Assessment Framework (IPCAF) survey, a previously validated structured questionnaire with an associated scoring system that evaluates the eight core components of IPC (IPC program; IPC guidelines; IPC education and training; healthcare-associated infection [HAI] surveillance; multimodal strategies; monitoring and audit of IPC practices and feedback; workload, staffing, and bed occupancy; and the built environment and materials and equipment for IPC). Each section generates a score 0-100. According to the final score, the HCF IPC program implementation is categorized into four levels: inadequate (0-200), basic (201-400), intermediate (401-600), or advanced (601-800). Additionally, we conducted semi-structured interviews among IPC personnel and microbiologists using the Systems Engineering Initiative for Patient Safety model to evaluate barriers and facilitators for IPC program implementation. We performed directed content analysis of interview transcripts to identify themes that focused on barriers and facilitators of IPC program implementation which are summarized descriptively. RESULTS: Thirty-seven HCFs (15 for-profit and 22 non-profit) completed the IPCAF survey. The overall median score was 614 (IQR 569, 693) which corresponded to an "advanced" level of IPC implementation (32% [7/22] non-profit vs. 93% [14/15] for-profit HCFs in this category). The lowest scores were in workload, staffing and bed occupancy followed by IPC training and multimodal strategies. Forty individuals from 16 HCFs were interviewed. They perceived inadequate staffing and technical resources, limited leadership support, and cultural determinants as major barriers to effective IPC guideline implementation, while external accreditation and technical support from public health authorities were perceived as facilitators. CONCLUSIONS: Efforts to strengthen IPC activities in Latin American HCFs should focus on improving support from hospital leadership and public health authorities to ensure better resource allocation, promoting safety culture, and improving training in quality improvement.

The Advisory Committee on Immunization Practices (ACIP) recommends that health care personnel receive an annual influenza vaccine. In September 2023, ACIP recommended that everyone aged ≥6 months receive a 2023-2024 COVID-19 vaccine. Health care facilities, including acute care hospitals and nursing homes, report vaccination of health care personnel against influenza and COVID-19 to CDC's National Healthcare Safety Network (NHSN). During October 2023-March 2024, NHSN defined up-to-date COVID-19 vaccination as receipt of a 2023-2024 COVID-19 vaccine. This analysis describes influenza and 2023-2024 COVID-19 vaccination coverage among health care personnel working in acute care hospitals and nursing homes during the 2023-24 respiratory virus season (October 1, 2023-March 31, 2024). Influenza vaccination coverage was 80.7% among health care personnel at acute care hospitals and 45.4% among health care personnel at nursing homes. Coverage of 2023-2024 COVID-19 vaccination was 15.3% among health care personnel at acute care hospitals and 10.5% among health care personnel at nursing homes. Respiratory viral diseases including influenza and COVID-19 pose risks to health care personnel in U.S. health care settings, and vaccination of health care personnel is an effective strategy for maintaining a healthy workforce and improving health care system resiliency.

BACKGROUND: Assessments of COVID-19 vaccine effectiveness are needed to monitor the protection provided by updated vaccines against severe COVID-19. We evaluated the effectiveness of original monovalent and bivalent (ancestral strain and Omicron BA.4/5) COVID-19 vaccination against COVID-19-associated hospitalization and severe in-hospital outcomes. METHODS: During September 8, 2022 to August 31, 2023, adults aged ≥ 18 years hospitalized with COVID-19-like illness were enrolled at 26 hospitals in 20 US states. Using a test-negative case-control design, we estimated vaccine effectiveness (VE) with multivariable logistic regression adjusted for age, sex, race/ethnicity, admission date, and geographic region. RESULTS: Among 7028 patients, 2924 (41.6%) were COVID-19 case patients, and 4104 (58.4%) were control patients. Compared to unvaccinated patients, absolute VE against COVID-19-associated hospitalization was 6% (-7%-17%) for original monovalent doses only (median time since last dose [IQR] = 421 days [304-571]), 52% (39%-61%) for a bivalent dose received 7-89 days earlier, and 13% (-10%-31%) for a bivalent dose received 90-179 days earlier. Absolute VE against COVID-19-associated invasive mechanical ventilation or death was 51% (34%-63%) for original monovalent doses only, 61% (35%-77%) for a bivalent dose received 7-89 days earlier, and 50% (11%-71%) for a bivalent dose received 90-179 days earlier. CONCLUSION: Bivalent vaccination provided protection against COVID-19-associated hospitalization and severe in-hospital outcomes within 3 months of receipt, followed by a decline in protection to a level similar to that remaining from previous original monovalent vaccination by 3-6 months. These results underscore the benefit of remaining up to date with recommended COVID-19 vaccines.

BACKGROUND: The COVID-19 pandemic raised unprecedented challenges to vaccinating children. This multi-center study aimed to compare on-time vaccination of children before and during the COVID-19 pandemic and identify key factors associated with on-time vaccination. METHODS: This study was conducted among children aged 0-6 years enrolled in the New Vaccine Surveillance Network at seven geographically diverse U.S. academic medical centers. Children with acute respiratory illness or acute gastroenteritis were enrolled from emergency department and inpatient settings; healthy control subjects were enrolled from primary care practices. Vaccination data were collected and verified from patient medical records, immunization information systems, and/or provider documentation. On-time vaccination according to Advisory Committee on Immunization Practices recommendations was compared between pre-pandemic (December 2018-February 2020) and pandemic (March 2020-August 2021) periods using bivariate and multivariable analyses, adjusting for key demographic, clinical, and study characteristics. RESULTS: A total of 24,713 children were included in the analytic sample (non-Hispanic 73.4 %; White 51.0 %; publicly insured 69.0 %). On-time vaccination declined between the pre-pandemic (67.3 %) and pandemic (65.4 %) periods (Adjusted Odds Ratio 0.89, 95 % CI 0.84-0.95). The largest declines were observed among children who were < 12 months, male, Black, publicly insured, or whose mothers had a high school-equivalent education or less. The pandemic impact also varied by vaccine type and study site. CONCLUSIONS: This multi-center study revealed a relatively modest overall reduction in on-time vaccination, which may reflect multilevel efforts to address pandemic-associated challenges. However, some patient subgroups and sites experienced greater reductions in on-time vaccination, highlighting the importance of tailoring interventions to increase equitable vaccine delivery, access, and acceptance across populations and communities.

In 2020, the World Health Assembly endorsed the Immunization Agenda 2030 (IA2030), a 10-year strategy to reduce vaccine-preventable disease (VPD)-associated morbidity and mortality. IA2030 goals include improving equitable vaccination coverage, halving the number of unimmunized (zero-dose) children, and increasing the introduction of new and underutilized vaccines. The COVID-19 pandemic disrupted health systems worldwide, hindering years of childhood vaccination achievements and putting global public health goals at risk. This report presents trends in World Health Organization (WHO) and UNICEF routine vaccination coverage estimates through 2023 across the 194 WHO member countries. During 2022-2023, global coverage with the first and third doses of diphtheria-tetanus-pertussis-containing vaccine (DTPcv) (89% and 84%, respectively) and the first dose of measles-containing vaccine (83%) stagnated and remained lower than prepandemic levels. The 31 WHO member countries with fragile, conflict-affected, and vulnerable (FCV) settings include approximately one half of the world's 14.5 million children who did not receive the first DTPcv dose. The introduction of new and underutilized vaccines, such as a second MCV dose in the African Region, has improved countries' overall protection against VPDs. Accelerating country-specific routine immunization and catch-up vaccination programs to reach unvaccinated and incompletely vaccinated children, especially those living in FCV settings, is critical to reducing morbidity and mortality associated with VPDs.

IMPORTANCE: Limited randomized clinical trial data exist on the safety of simultaneous administration of COVID-19 and influenza vaccines. OBJECTIVE: To compare the reactogenicity, safety, and changes in health-related quality of life (HRQOL) after simultaneous vs sequential receipt of messenger RNA (mRNA) COVID-19 vaccine and quadrivalent inactivated influenza vaccine (IIV4). DESIGN, SETTING, AND PARTICIPANTS: This randomized, placebo-controlled clinical trial was conducted between October 8, 2021, and June 14, 2023, at 3 US sites. Participants were nonpregnant persons aged 5 years or older with the intention of receiving both influenza and mRNA COVID-19 vaccines. INTERVENTIONS: Intramuscular administration in opposite arms of either IIV4 or saline placebo simultaneously with mRNA COVID-19 vaccine at visit 1. Those who received placebo at visit 1 received IIV4 and those who received IIV4 at visit 1 received placebo 1 to 2 weeks later at visit 2. MAIN OUTCOMES AND MEASURES: The primary composite reactogenicity outcome was the proportion of participants with fever, chills, myalgia, and/or arthralgia of moderate or greater severity within 7 days after vaccination visits 1 and/or 2, using a 10% noninferiority margin. Secondary outcomes were solicited reactogenicity events and unsolicited adverse events (AEs) for 7 days after each visit separately and HRQOL after visit 1, assessed by the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Index. Serious AEs (SAEs) and AEs of special interest (AESIs) were assessed for 121 days. Outcomes were compared between groups. RESULTS: A total of 335 persons (mean [SD] age, 33.4 [15.1] years) were randomized (169 to the simultaneous group and 166 to the sequential group); 211 (63.0%) were female, and 255 (76.1%) received bivalent BNT162b2 mRNA COVID-19 vaccine. The proportion with the primary composite reactogenicity outcome in the simultaneous group (25.6% [n = 43]) was noninferior to the proportion in the sequential group (31.3% [n = 52]) (site-adjusted difference, -5.6 percentage points [pp]; 95% CI, -15.2 to 4.0 pp). Respective proportions in each group were similar after each visit separately (visit 1, 40 [23.8%] vs 47 [28.3%]; visit 2, 5 [3.0%] vs 9 [5.4%]). No significant group differences in participants with AEs (21 [12.4%] vs 16 [9.6%]), SAEs (1 [0.6%] vs 1 [0.6%]), and AESIs (19 [11.2%] vs 9 [5.4%]) were observed in the simultaneous vs sequential groups, respectively. Among participants with severe reactogenicity, the mean (SD) EQ-5D-5L Index score decreased from 0.92 (0.08) to 0.92 (0.09) prevaccination to 0.81 (0.09) to 0.82 (0.12) postvaccination. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial assessing simultaneous vs sequential administration of mRNA COVID-19 and IIV4 vaccines, reactogenicity was comparable in both groups. These findings support the option of simultaneous administration of these vaccines. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05028361.

Background: Many studies rely on the International Classification of Diseases, 9th or 10th Revision, Clinical Modification codes to define obesity in electronic health records data. While prior studies found misclassification and low sensitivity of codes for pediatric obesity, it remains unclear whether this misclassification is random and what are the implications of combining different code types to define obesity. Methods: We assessed prevalence, sensitivity, and specificity of obesity codes among 7.4 million children aged 2-19 years over 2014-2021. Among those with obesity in 2021, we estimated the probability of receiving any code or a specific code type by patient characteristics. Results: Obesity code utilization increased in prevalence from 3.9% in 2014 to 9.8% in 2021; prevalence of obesity based on BMI increased from 17.4% to 20.5%. Code sensitivity increased from 19.8% to 40.8%. Among children with obesity in 2021, those with severe obesity (reference: no severe obesity) and chronic disease (reference: no chronic disease) were more likely to get a code, and the highest likelihood was associated with obesity diagnosis codes (vs. status codes). Conclusions: Despite increases, obesity code utilization remained low. Obesity code misclassification is not random and certain child characteristics (e.g., severe obesity or chronic disease) are associated with a higher probability of getting a code. There are also significant differences by code type; thus, caution should be taken before combining obesity codes as a proxy for obesity status, especially in longitudinal analyses. More universal documentation of obesity may improve the quality of care and the use of these data for evaluation and research purposes.

Common methods to collect data include quantitative, qualitative, and mixed method approaches. Although it is common to complete data collection in-person, the onset of COVID-19 has resulted in the increased use of online modalities. Qualitative research is commonly gathered through individual or focus group interviews. However, best practices outlining strategies when conducting online focus groups and approaches to address issues specific to online research (i.e., scammers) are limited. Due to the growing use of data collection through such means, it is imperative to draw out specific strategies that could regulate data quality and reduce the chances of scamming. The current article addresses this practical gap by providing a synthesis of the available literature on online focus groups that document best practices and suggestions to deal with scammers which is currently missing from the literature. The goal was to provide initial suggestions to improve data quality of online focus groups by examining the available literature that outlines best practices, addresses the issues of scammers, and to provide a concise and comprehensive overview of identified literature The article is organized beginning with a review of the literature. The research is then synthesized including an outline of best practices and strategies to address scammers when engaging in online focus groups. The article closes with a discussion of the significance of the review, limitations, and article summary. Scammers are prevalent in online spaces. Although this article provides a preliminary outline of suggestions from the literature, more research is necessary that provides specific examples of how challenges have been addressed and the impact of including the recommended strategies on the research process and outcomes. © 2024, Ludomedia EN. All rights reserved.

Adverse childhood experiences (ACEs) are common and can impact health across the life course. Thus, it is essential for professionals in child- and family-serving roles, including pediatric and adult primary care clinicians, to understand the health implications of childhood adversity and trauma and respond appropriately. Screening for ACEs in health care settings has received attention as a potential approach to ACEs identification and response. Careful examination of the existing evidence on ACEs screening and consideration, from a clinical and ethical perspective, of the potential benefits, challenges, and harms is critical to ensuring evidence-informed practice. In this critical appraisal, we synthesize existing systematic and scoping reviews on ACEs screening, summarize recent studies on the ability of ACEs to predict health outcomes at the individual level, and provide a comprehensive overview of potential benefits, challenges, and harms of ACEs screening. We identify gaps in the existing evidence base and specify directions for future research. We also describe trauma-informed, relational care as an orientation and perspective that can help pediatric and primary care clinicians to sensitively assess for and respond to ACEs and other potentially traumatic experiences. Overall, we do not yet have sufficient evidence regarding the potential benefits, challenges, and harms of ACEs screening in health care and other settings. In the absence of this evidence, we cannot assume that screening will not cause harm and that potential benefits outweigh potential harms.

OBJECTIVES: Drowning is the leading cause of death during flood disasters. Little is known about these deaths. Child death review teams review details of child deaths to understand circumstances and risk factors to inform prevention. METHODS: Using data entered in 2005 to 2021 for children ages 0 to 17 years from the National Fatality Review-Case Reporting System, we identified 130 drowning deaths directly attributed to natural disaster or weather incidents, and 14 deaths indirectly attributed to these incidents. Frequencies, proportions, and χ2 statistics were used to describe selected measures and compare with other drowning deaths. RESULTS: Children who drowned as a direct result of a natural disaster- or weather-related incident were more likely to be aged >4 years (81% vs 40%, P < .001) and located in a rural or frontier setting (63% vs 30%, P < .001). They were more likely to be supervised at the time of the incident (61% vs 38%, P < .001), and it was more likely for additional children (35% vs 5%, P < .001) or adults (33% vs 3%, P < .001) to have perished. The indirect deaths were commonly a result of damage to protective barriers. CONCLUSIONS: The characteristics of natural disaster- or weather-related drowning deaths among children differ from other drowning deaths. Natural disaster- or weather-related drowning may warrant tailored drowning prevention strategies. Improved surveillance of all water-related deaths may be a proactive action leading to the development of these prevention strategies, whereas poststorm remediation of protective barriers can be used as a reactive prevention after a storm has passed.

BACKGROUND: Limited research exists on suicide among children aged 5 to 9 years. The objective of this study was to examine characteristics of suicide in children younger than 10 years. METHODS: Data are from the National Fatality Review-Case Reporting System (NFR-CRS) for years 2006 through 2021 for children aged 6 to 9 years who died by suicide. No suicide deaths were reported in NFR-CRS for children aged ≤ 5 years. Descriptive analyses by demographics and circumstances were conducted. A thematic analysis of prevention recommendations made by child death review teams was performed. RESULTS: From 2006 to 2021, NFR-CRS identified 78 suicide decedents aged 6 to 9 years. The largest share were aged 9 years (72%), male (74%), non-Hispanic Black (42%), and died by hanging (86%) at home (91%). School-related problems (39%), history of child maltreatment (36%), history of mental health services (30%), argument with parents (23%), and familial discord (19%) were common circumstances. Key suicide prevention themes included education for caregivers and school staff, improved behavioral health services, and implementation of school policies and programs. CONCLUSIONS: Results provide a more complete picture of suicide among younger children, improving understanding of their unique characteristics. It is recommended that program planners consider both age-appropriateness and the impacts of social (eg, racism) and structural inequities in their approaches to prevention, encompassing both community and school-based strategies. For pediatricians, results emphasize the importance of lethal means counseling, safety planning, and educating parents and caregivers on the distinct warning signs of suicide for younger children.

Natural toxins present an ongoing risk for human exposure that requires a rapid, accurate diagnosis for proper response. In this study, a qualitative liquid chromatography high resolution mass spectrometry (LC-HRMS) method was developed and validated for the detection of a large, diverse selection of natural toxins. Data-dependent acquisition was performed to identify compounds with an in-house mass spectral library of 129 hazardous toxins that originate from plants, animals, and fungi. All 129 compounds were spiked into human urine, extracted, and evaluated for spectral library matching. Of these, 92 toxins met the quality criteria and underwent validation in urine matrix based on American National Standards Institute (ANSI) guidelines. A generalized workflow for method expansion was developed and enables the rapid addition of relevant compounds to the established method. This LC-HRMS method achieves efficient detection of natural toxins in urine, and the created workflow can rapidly increase compound coverage via method expansion.

AIM: Lipoprotein (a) [Lp(a)] is a well-established risk factor for cardiovascular disease independent of low-density lipoprotein-cholesterol (LDL-C). The Lp(a) concentrations were inconsistent between the immunoassays. This study aimed to investigate whether harmonization of Lp(a) measurements can be achieved using a serum panel value assigned with the IFCC-endorsed mass spectrometry-based reference measurement procedure (IFCC-MS-RMP). METHODS: We measured the Lp(a) concentrations using five Lp(a) immunoassays in 40 panel sera provided by the Centers for Disease Control and Prevention (CDC), and 500 Japanese subjects enrolled in the Bunkyo Health Study. Of the five immunoassays, only the Roche Lp(a) assay was traceable to the WHO-IFCC reference material SRM2B. Lp(a) concentrations in CDC samples were also determined by IFCC-MS-RMP, provisionally calibrated to SRM2B. Lp(a) concentrations were expressed in mass units (mg/dL) for most reagents, but in SI units (nmol/L) for Roche's reagent and IFCC-MS-RMP. RESULTS: In the CDC panel sera, all immunoassays, including Roche's reagent, showed good correlations with IFCC-MS-RMP. In the Bunkyo Health Study samples, all immunoassays showed good correlations with Roche's reagent (r(s), 0.986-0.998) although the slopes of the regression lines ranged from 0.292 to 0.579. After recalibration with the CDC's panel sera, Lp(a) results of Bunkyo Health Study samples were converted to the equivalent values determined by the IFCC-MS-RMP, thus resulting in a marked reduction in the intermethod CV among the assays. CONCLUSION: We achieved harmonization of Lp(a) measurements with five immunoassays using a serum panel value assigned with the IFCC-MS-RMP.

BACKGROUND: Experimental studies have shown associations between gestational phthalate exposure and behavioral problems among offspring; however, epidemiological evidence is still mixed. This study aims to investigate whether gestational phthalate exposure is associated with behavioral problems in preschool-aged children. METHODS: Participants include 178 mother-child pairs from MARBLES (Markers of Autism Risk in Babies - Learning Early Signs), a cohort with high familial likelihood of autism spectrum disorder (ASD). We quantified 14 phthalate metabolites in multiple maternal urine samples collected during the 2nd and 3rd trimesters. Preschool behavior problems were assessed using the Child Behavioral Checklist (CBCL), a standardized instrument for evaluating behavior problems of children aged 1.5-5 years. To examine associations of CBCL scores with both individual phthalate biomarker concentrations and their mixture, we used negative binomial regression and weighted quantile sum regression. RESULTS: Overall, maternal phthalate biomarker concentrations were not associated with child behavior problems. Monoisobutyl phthalate (MiBP) concentrations were inversely associated with child anxious/depressed symptoms and somatic complaints. Mono-hydroxy-isobutyl phthalate (MHiBP) and monobenzyl phthalate (MBzP) were also inversely associated with somatic complaints. When assessing trimester-specific associations, more behavior problems were associated with the 2nd trimester biomarker concentrations: mono(3-carboxypropyl) phthalate (MCPP) and monocarboxyisononyl phthalate (MCNP) were positively associated with somatic complaints. All associations became non-significant after false discovery rate correction. No association between a mixture of phthalates and CBCL scores was found. CONCLUSIONS: Our study observed no clear evidence of gestational phthalate exposure on child behavior problems. However, our findings based on the biomonitoring assessment of multiple samples per participant could improve our understanding of gestational phthalate exposure in association with behavior problems in preschool-aged children.

OBJECTIVES: To describe sudden unexpected infant deaths (SUIDs) occurring in safe sleep environments and explore differences in selected characteristics. METHODS: We examined SUID from 22 jurisdictions from 2011 to 2020 and classified them as unexplained, no unsafe sleep factors (U-NUSF). Data were derived from the Sudden Unexpected Infant Death and Sudden Death in the Young Case Registry, a population-based Centers for Disease Control and Prevention surveillance system built on the National Center for Fatality Review and Prevention's child death review program. SUID classified as U-NUSF included infants who were (1) awake, under supervision, and witnessed to become unresponsive or (2) found unresponsive in a safe sleep environment after sleep (unwitnessed). We calculated frequencies and percentages for demographics, birth and environmental characteristics, medical history, and death investigation findings. RESULTS: Most of the 117 U-NUSF SUID occurred before 4 months of age. Witnessed deaths most commonly occurred at <1 month of age (28%), whereas unwitnessed deaths most commonly occurred at ages 2 to 3 months (44%) Among all U-NUSF, 69% occurred in the infant's home (62% witnessed, 77% unwitnessed). All unwitnessed deaths occurred in a crib; most witnessed deaths occurred while being held (54%) or in a car seat traveling (18%). Most infants (84%) had no history of abuse or neglect. Abnormal autopsy findings were reported in 46% of deaths (49% witnessed, 42% unwitnessed). CONCLUSIONS: Characterizing these deaths is key to advancing our knowledge of SUID etiology. Our study revealed a heterogeneous group of infants, suggesting physiologic, genetic, or environmental etiologies.

The landscape of research on the benefits of influenza vaccines and antivirals to protect pregnant persons and infants has increased in recent years, while influenza vaccination rates and antiviral usage have declined. Pregnant people and infants <6 months of age are at increased risk of hospitalization with influenza, making protection of this population essential. Maternal influenza vaccination at any time during pregnancy is the best way to reduce the risk of influenza and severe influenza in both pregnant people and their infants <6 months of age. Influenza antiviral medications for pregnant people and infants are also recommended as early as possible if influenza is confirmed or suspected. This report will update on the current research on the benefits of influenza vaccination during pregnancy and influenza antiviral medication for the pregnant person and infant, current Advisory Committee on Immunization Practices recommendations for influenza vaccination in pregnancy and vaccination coverage rates, current influenza antiviral medication guidance and usage rates in pregnancy and among infants, and future directions for influenza pregnancy research. With over half a century of maternal influenza vaccination in the United States, we have improved protection for pregnant persons and infants against influenza, but we still have room for improvement and optimization with new challenges to overcome following the COVID-19 pandemic. By continuing to fill research gaps and increase vaccination coverage and antiviral usage, there is potential for significant reductions in the domestic and global burden of influenza in pregnant persons and infants.

Pregnancy is associated with increased risk for severe illness and complications associated with influenza infection. Insufficient knowledge about the risk for influenza among pregnant women and their health care providers in China is an important barrier to increasing influenza vaccination coverage and treating influenza and its complications among pregnant women. Improved influenza incidence estimates might promote wider vaccine acceptance and higher vaccination coverage. In Suzhou, active population-based surveillance during October 2018-September 2023 estimated that the annual rate of hospitalization for acute respiratory or febrile illness (ARFI) among women who were pregnant or <2 weeks postpartum was 11.1 per 1,000 live births; the annual rate of laboratory-confirmed influenza-associated ARFI (influenza ARFI) hospitalization in this group was 2.1 per 1,000 live births. A majority of hospitalized pregnant or early postpartum patients with ARFI (82.6%; 2,588 of 3,133) or influenza ARFI (85.5%; 423 of 495) were admitted to obstetrics wards rather than respiratory medicine wards. Only one (0.03%) pregnant or postpartum ARFI patient had received influenza vaccination, and 31.3% of pregnant or postpartum women hospitalized for influenza ARFI received antiviral treatment; the lowest percentage of hospitalized women with influenza ARFI who received antiviral treatment was among women admitted to obstetrics and gynecology wards (29.6% and 23.1%, respectively), compared with 54.1% of those admitted to a respiratory medicine ward. These findings highlight the risk for influenza and its associated complications among pregnant and postpartum women, the low rates of influenza vaccination among pregnant women, and of antiviral treatment of women with ARFI admitted to obstetrics and gynecology wards. Increasing awareness of the prevalence of influenza ARFI among pregnant women, the use of empiric antiviral treatment for ARFI, and the infection control in obstetrics wards during influenza seasons might help reduce influenza-associated morbidity among pregnant and postpartum women.

BACKGROUND: Double-fortified salt (DFS; iron, iodine) improved iron status in randomized trials and was incorporated into India's social safety net programs, suggesting opportunities to address other micronutrient deficiencies. OBJECTIVES: To evaluate acceptability of quadruple-fortified salt (QFS; iron, iodine, folic acid, vitamin B(12)) in women and their households, using a randomized crossover trial design and triangle tests. METHODS: Women 18-49y (n=77) and their households were randomized to receive QFS or DFS in a randomized crossover design over a 3-week period (week 1: QFS/DFS, 2: iodized salt, 3: DFS/QFS). Each week, participants completed a 9-point hedonic questionnaire (1=dislike extremely to 9=like extremely) to evaluate five sensory domains (color, odor, taste, texture, overall acceptability) of the intervention, and remaining salt was weighed using a digital scale. Triangle tests were conducted among women to evaluate sensory discrimination of salt consumed in rice dishes prepared using standardized recipes. Mixed models were used to examine hedonic ratings and salt use; salt type, sequence, and period were included as fixed effects, and household was included as a random effect. Binomial tests were used to evaluate sensory discrimination of salt type in triangle tests. RESULTS: Mean hedonic ratings for most of the five sensory domains were ≥7 (like moderately) and did not differ by salt type (overall acceptability mean [SD]: QFS: 7.8 [0.7] vs. DFS: 7.7 [1.2]; p=0.68). Household salt use (weighed) did not differ by salt type. During the 3-week intervention period, weighed salt use and hedonic ratings significantly increased, indicating a period effect independent of salt type or sequence. In triangle tests, rice samples prepared with QFS, DFS, or iodized salt were not distinguishable. CONCLUSION: Acceptability of QFS was high, based on individual hedonic ratings and weighed household salt use. Rice dishes prepared with DFS, QFS, and iodized salt were not distinguishable. Findings informed the design of a randomized trial of QFS in this population. REGISTRATION NUMBERS: NCT03853304 and REF/2019/03/024479.

A very small proportion of all chemicals in commerce have occupational exposure limits (OELs) based on quantitative risk assessments which require estimates of exposure-response relationships (XRs). For only 18 of the 94 chemicals declared by NIOSH to be carcinogens were human XRs reported in or calculable from published reports. For the 18 carcinogens, 96 such XRs could be derived (corresponding to chemicals with multiple associated cancer end-points and/or multiple source studies). Twenty-four of 96 XR estimates came directly from reported statistical models (on continuous cumulative exposure), 45 were derived from summary study-population attributes, and 27 came from categorical analyses. Using the 96 XRs, OEL conferring one-per-thousand excess lifetime risk were calculated. OSHA's OEL, permissible exposure limits (PEL) were then compared to OEL derived from the 96 XRs. For 88 of the 96 calculated OELs (for which a corresponding PEL exists) all but 10 fell below the current PEL. Thirty-four OEL estimates were 10- to 100-fold below the PEL and 21 were greater than 100-fold below the PEL. This same pattern was observed using the different methods for deriving XRs. These findings can guide priorities in setting standards and the method is not limited to carcinogens.

Globally, nearly half of all pregnancies are unintended, ~1.3 million new human immunodeficiency virus (HIV) infections are reported every year, and more than 500 million people are estimated to have a genital herpes simplex virus (HSV-2) infection. Here we report the first 3D printed multipurpose prevention technology (MPT) intravaginal ring (IVR) for prevention of HIV, HSV-2, and unintended pregnancy. The IVRs were fabricated using state-of-the-art Continuous Liquid Interface Production (CLIP™) 3D printing technology using a biocompatible silicone-urethane based resin. Anti-HIV drug (Dapivirine, DPV), anti-herpes drug (Pritelivir, PTV) and a contraceptive drug (Levonorgestrel, LNG) were loaded in a macaque size IVR (25 mm outer diameter, OD; 6.0 mm cross-section, CS) allometrically scaled from the human size (54 mm OD; 7.6 mm CS) IVR analogue. All three active pharmaceutical ingredients (APIs) were loaded in the IVR using a single-step drug loading process driven by absorption. DPV, PTV, and LNG elicited zero-order release kinetics in vitro in simulated vaginal fluid (SVF) at pH 4 and pH 8 relevant to human and macaque vaginal pH respectively. CLIP 3D printed MPT IVRs remained stable after 6 months of storage at 4 °C with no change in physical, dimensional, or mechanical properties and no change in drug concentration and absence of drug degradation byproducts. The MPT IVRs elicited sustained release of all three APIs in macaques for 28 days with median plasma concentrations of 138 pg/mL (DPV), 18,700 pg/mL (PTV), and 335 pg/mL (LNG). Safety studies demonstrated that the MPT IVRs were safe and well tolerated in the macaques with no observed change or abnormalities in vaginal pH and no significant changes in any of the 22 mucosal cytokines and chemokines tested including pro-inflammatory (IL-1β, IL-6, IL-8, IFN-γ, TNF-α, IL-17, IL-18) and anti-inflammatory (IL-10, IL-12) cytokines while the MPT IVR was in place or after its removal. Additionally, MPT IVRs elicited no observed alterations in systemic CD4+ and CD8+ T cells during the entire study. Collectively, the proposed MPT IVR has potential to expand preventative choices for young women and girls against unintended pregnancy against two highly prevalent sexually transmitted infections (STIs).

Cutaneous myiasis caused by various Calliphoridae dipteran species is prevalent worldwide and is of particular veterinary and public health concern. Recently, in a scientific exploration of the Guinea Worm Eradication Program to Chad, Africa, we observed that dogs with mutilated ears, based on local awareness, were caused by cutaneous myiasis. In this study, we analyzed epidemiological, morphological, and molecular data on cutaneous myiasis in dogs from Chad. From September to October 2022, dogs (n = 1,562) from 56 villages situated along the Chari River were physically inspected for cutaneous myiasis. All larvae were collected and identified morphologically and by molecular analysis of the partial cytochrome oxidase c subunit I (COI) mitochondrial gene. The prevalence of myiasis infestation along with 95% confidence intervals (95% CI) was determined using the modified Wilson method. Myiasis was detected in dogs from 21 villages (37.5%; 95% CI 26 - 50%), predominating in the southernmost region. Of 1,562 dogs, 66 (4.22%; 95% CI 3.34 - 5.34%) were infested by calliphorid larvae, with a mean infestation of 2.28 larvae per animal (range = 1 to 24). Specimens were morphologically identified as Cordylobia anthropophaga (n = 94), Chrysomya bezziana (n = 54), and Chrysomya sp. (n = 3), which were detected in 57, eight and one dog, respectively. No co-infestations were observed. The molecular analyses confirmed the morphological identification and revealed the presence of 17 haplotypes for C. anthropophaga, 2 for C. bezziana, and one for Chrysomya sp. Our study emphasizes the veterinary importance of myiasis in dogs in Africa and proposes measures to assure their health and well-being.

Rocky Mountain spotted fever (RMSF) is an ongoing public health crisis in Mexico, particularly in states bordering the United States. The national highest incidence and mortality of RMSF occur in this region, resulting in a case-fatality rate that ranges annually between 10% and 50%, primarily affecting vulnerable groups such as children, elderly adults, and persons living in poverty. Multiple biological, environmental, and social determinants can explain its growing presence throughout the country and how it challenges the health system and society. It is necessary to integrate resources and capacities from health authorities, research centers, and society to succeed in dealing with this problem. Through a scientific symposium, a group of academicians, U.S. health officials, and Mexican health authorities met on November 8-10, 2023, in Hermosillo, Mexico, to discuss the current situation of RMSF across the country and the challenges associated with its occurrence. An urgent call for action to improve national capacity against RMSF in the aspects of epidemiological and acarological surveillance, diagnosis, medical care, case and outbreak prevention, health promotion, and research was urged by the experts. The One Health approach is a proven multidisciplinary strategy to integrate policies and interventions to mitigate and prevent the burden of cases, deaths, and suffering caused by RMSF in Mexico.

We report a patient in North Carolina, USA, with Heartland virus infection whose diagnosis was complicated by previous Ehrlichia chaffeensis infection. We identified E. ewingii-infected and Bourbon virus-infected tick pools at the patient's residence. Healthcare providers should consider testing for tickborne viruses if ehrlichiosis is suspected.

BACKGROUND: Pyrethroid-chlorfenapyr nets have shown significant epidemiological impact over pyrethroid-only and pyrethroid plus piperonyl-butoxide (PBO) in Africa. A non-inferiority evaluation of PermaNet(®) Dual, a new chlorfenapyr plus deltamethrin net, compared to Interceptor(®) G2, was conducted in experimental huts in Siaya, Kenya against free-flying pyrethroid-resistant Anopheles funestus. METHODS: This study was an experimental hut trial, following a 7 by 7 Latin Square design. Seven treatments and seven sleepers were deployed in the experimental huts daily and rotated weekly and daily, respectively. Mosquitoes were collected every morning between 06:30 h and 08:30 h and were assessed for blood feeding and then monitored for immediate knockdown 1-h post collection and delayed mortality after 72 h. Differences in proportional outcomes were analysed using the blocked logistic regression model, while differences in numerical outcomes were analysed using the negative binomial regression model. Non-inferiority determination was performed based on World Health Organization (WHO) protocol. RESULTS: Mortality at 72 h was 30.2% for PermaNet 3.0, 44.4% for the Interceptor(®) G2 and 49.2% for the PermaNet(®) Dual. Blood feeding was highest with PermaNet(®) Dual at 15%, and least with PermaNet(®) 3.0 at 10%. PermaNet(®) Dual and Interceptor(®) G2 had no significant differences in mortality (OR = 1.10, 95% CI 1.00-1.20) or blood feeding (OR = 1.18, 95% CI 1.04-1.33) and the lower confidence bounds were within the non-inferiority margins but for blood feeding, non-inferiority was relatively high to the upper 95% confidence bound. PermaNet(®) Dual was non-inferior to the Interceptor(®) G2 and superior to the PermaNet(®) 3.0 nets in causing mortality but inferior to PermaNet (®)3.0 in blood feeding inhibition of the vectors. CONCLUSION: PermaNet(®) Dual met the WHO criteria for non-inferiority to Interceptor(®) G2 and may be considered for deployment for public health use against pyrethroid-resistant Anopheles vectors of malaria.

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

Habitat loss and forest fragmentation are often linked to increased pathogen transmission, but the extent to which habitat isolation and landscape connectivity affect disease dynamics through movement of disease vectors and reservoir hosts has not been well examined. Tick-borne diseases are the most prevalent vector-borne diseases in the United States and on the West Coast, Ixodes pacificus is one of the most epidemiologically important vectors. We investigated the impacts of habitat fragmentation on pathogens transmitted by I. pacificus and sought to disentangle the effects of wildlife communities and landscape metrics predictive of pathogen diversity, prevalence and distribution. We collected pathogen data for four co-occurring bacteria transmitted by I. pacificus and measured wildlife parameters. We also used spatial data and cost-distance analysis integrating expert opinions to assess landscape metrics of habitat fragmentation. We found that landscape metrics were significant predictors of tick density and pathogen prevalence. However, wildlife variables were essential when predicting the prevalence and distribution of pathogens reliant on wildlife reservoir hosts for maintenance. We found that landscape structure was an informative predictor of tick-borne pathogen richness in an urban matrix. Our work highlights the implications of large-scale land management on human disease risk.