Estimating hepatitis C prevalence in the United States, 2017-2020.

BACKGROUND AIMS: The National Health and Nutrition Examination Survey (NHANES) underestimates the true prevalence of hepatitis C virus (HCV) infection. By accounting for populations inadequately represented in NHANES, we created two models to estimate the national hepatitis C prevalence among US adults during 2017-2020. APPROACH RESULTS: The first approach (NHANES+) replicated previous methodology by supplementing hepatitis C prevalence estimates among the US noninstitutionalized civilian population with a literature review and meta-analysis of hepatitis C prevalence among populations not included in the NHANES sampling frame. In the second approach (persons who inject drugs [PWID] adjustment), we developed a model to account for underrepresentation of PWID in NHANES by incorporating the estimated number of adult PWID in the United States and applying PWID-specific hepatitis C prevalence estimates. Using the NHANES+ model, we estimated HCV RNA prevalence of 1.0% (95% confidence interval [CI]: 0.5%-1.4%) among US adults in 2017-2020, corresponding to 2,463,700 (95% CI: 1,321,700-3,629,400) current HCV infections. Using the PWID adjustment model, we estimated HCV RNA prevalence of 1.6% (95% CI: 0.9%-2.2%), corresponding to 4,043,200 (95% CI: 2,401,800-5,607,100) current HCV infections. CONCLUSIONS: Despite years of an effective cure, estimated prevalence of hepatitis C in 2017-2020 remains unchanged from 2013-2016 when using comparable methodology. When accounting for increased injection drug use, estimated prevalence of hepatitis C is substantially higher than previously reported. National action is urgently needed to expand testing, increase access to treatment, and improve surveillance, especially among medically underserved populations, to support hepatitis C elimination goals.

Estimated Number of Injection-Involved Overdose Deaths in US States From 2000 to 2020: Secondary Analysis of Surveillance Data.

BACKGROUND: In the United States, both drug overdose mortality and injection-involved drug overdose mortality have increased nationally over the past 25 years. Despite documented geographic differences in overdose mortality and substances implicated in overdose mortality trends, injection-involved overdose mortality has not been summarized at a subnational level. OBJECTIVE: We aimed to estimate the annual number of injection-involved overdose deaths in each US state from 2000 to 2020. METHODS: We conducted a stratified analysis that used data from drug treatment admissions (Treatment Episodes Data Set-Admissions; TEDS-A) and the National Vital Statistics System (NVSS) to estimate state-specific percentages of reported drug overdose deaths that were injection-involved from 2000 to 2020. TEDS-A collects data on the route of administration and the type of substance used upon treatment admission. We used these data to calculate the percentage of reported injections for each drug type by demographic group (race or ethnicity, sex, and age group), year, and state. Additionally, using NVSS mortality data, the annual number of overdose deaths involving selected drug types was identified by the following specific multiple-cause-of-death codes: heroin or synthetic opioids other than methadone (T40.1, T40.4), natural or semisynthetic opioids and methadone (T40.2, T40.3), cocaine (T40.5), psychostimulants with abuse potential (T43.6), sedatives (T42.3, T42.4), and others (T36-T59.0). We used the probabilities of injection with the annual number of overdose deaths, by year, primary substance, and demographic groups to estimate the number of overdose deaths that were injection-involved. RESULTS: In 2020, there were 91,071 overdose deaths among adults recorded in the United States, and 93.1% (84,753/91,071) occurred in the 46 jurisdictions that reported data to TEDS-A. Slightly less than half (38,253/84,753, 45.1%; 95% CI 41.1%-49.8%) of those overdose deaths were estimated to be injection-involved, translating to 38,253 (95% CI 34,839-42,181) injection-involved overdose deaths in 2020. There was large variation among states in the estimated injection-involved overdose death rate (median 14.72, range 5.45-31.77 per 100,000 people). The national injection-involved overdose death rate increased by 323% (95% CI 255%-391%) from 2010 (3.78, 95% CI 3.33-4.31) to 2020 (15.97, 95% CI 14.55-17.61). States in which the estimated injection-involved overdose death rate increased faster than the national average were disproportionately concentrated in the Northeast region. CONCLUSIONS: Although overdose mortality and injection-involved overdose mortality have increased dramatically across the country, these trends have been more pronounced in some regions. A better understanding of state-level trends in injection-involved mortality can inform the prioritization of public health strategies that aim to reduce overdose mortality and prevent downstream consequences of injection drug use.

Development of a University-Government Partnership for Public Health Response and Workforce Development in the State of Oregon.

The COVID-19 pandemic exposed and exacerbated a public health workforce shortage and national strategies have called for the development of clear occupational pathways for students to enter the public health workforce and meaningful public health careers. In response to the immediate need for public health workers during the pandemic, several universities and academic hospitals rapidly mobilized students and employees and partnered with local or state health departments. However, many of those partnerships were based on short-term volunteer effort to support critical COVID-19 public health efforts. In this article, we document the development of Oregon's Public Health Practice Team, a student, staff, and faculty workforce developed at the Oregon Health & Science University-Portland State University (OHSU-PSU) School of Public Health in close collaboration with the Oregon Health Authority (OHA). This project contributed significant effort to several phases of Oregon's statewide public health response to COVID-19, and over time developed into a lasting, multi-purpose, inter-agency collaborative public health practice program. Health equity has been centered at every stage of this work. We describe the phases of the partnership development, the current team structure and operations, and highlight key challenges and lessons learned. This provides a case-study of how an innovative and flexible university-government partnership can contribute to immediate pandemic response needs, and also support ongoing public health responses to emerging needs, while contributing to the development of a skilled and diverse public health workforce.

Role of a Nursing Informatics Specialist in a Clinical Simulation Laboratory:: The Catalytic Link.

BACKGROUND: Technology in health care is pervasive and growing exponentially. Simulation in academic settings also continues to expand with the use of advancing technologies. PROBLEM: Technology appropriate usage and implementation can become problematic without experts with the right skills in nursing simulation labs. Gaps in technology utilization, simulation best practices, and data analytics now exist. APPROACH: A school of nursing employed a nurse informaticist in its simulation laboratory to address the complexities of technology usage and aid in data analytics. OUTCOMES: The nurse informaticist was effective at promoting simulation use, increasing faculty and learner usage of the simulation space. The initiation of data capturing was also achieved. CONCLUSIONS: Highly trained nurse informaticists are ready to address the unique complexities of advanced simulation environments.

The effects of affect-guided interval training on pleasure, enjoyment, and autonomy: A registered report.

This registered report tested the effects of a novel exercise protocol, namely affect-guided interval training, on motivationally relevant variables of remembered pleasure, forecasted pleasure, enjoyment, and autonomy. Affect-guided interval training (AIT) consisted of 60-s intervals that alternated between the highest pleasant intensity and lowest pleasant intensity for 20 min; this was intended to minimize the potential displeasure of traditional high-intensity interval training. The novel protocol was compared to self-selected exercise intensity (30 min) and high-intensity interval training (60-s intervals for 20 min). All sessions were, on average, vigorous in intensity (80-89% peak heart rate). Data indicate that the AIT session was experienced as the most pleasant, had the most pleasant slope of affect, was remembered as the most pleasant, resulted in the most positive affective forecasts, and was the most enjoyable. Both the affect-guided interval session and self-selected exercise session resulted in greater autonomy than high-intensity interval training. Several evaluative and motivationally relevant variables, including (a) remembered pleasure, (b) enjoyment, and (c) forecasted pleasure were predicted by (a) experienced pleasure, the (b) pleasure experienced at the end of exercise, and (c) the slope of pleasure experienced throughout the exercise session. Overall, this study suggests that affect-guided interval training is a feasible and positive alternative that can be included as a viable option for exercise programming.

Cytoneme signaling provides essential contributions to mammalian tissue patterning.

During development, morphogens pattern tissues by instructing cell fate across long distances. Directly visualizing morphogen transport in situ has been inaccessible, so the molecular mechanisms ensuring successful morphogen delivery remain unclear. To tackle this longstanding problem, we developed a mouse model for compromised sonic hedgehog (SHH) morphogen delivery and discovered that endocytic recycling promotes SHH loading into signaling filopodia called cytonemes. We optimized methods to preserve in vivo cytonemes for advanced microscopy and show endogenous SHH localized to cytonemes in developing mouse neural tubes. Depletion of SHH from neural tube cytonemes alters neuronal cell fates and compromises neurodevelopment. Mutation of the filopodial motor myosin 10 (MYO10) reduces cytoneme length and density, which corrupts neuronal signaling activity of both SHH and WNT. Combined, these results demonstrate that cytoneme-based signal transport provides essential contributions to morphogen dispersion during mammalian tissue development and suggest MYO10 is a key regulator of cytoneme function.

Radiation cataract in Heterogeneous Stock mice after γ-ray or HZE ion exposure.

Health effects of space radiation are a serious concern for astronauts on long-duration missions. The lens of the eye is one of the most radiosensitive tissues in the body and, therefore, ocular health risks for astronauts is a significant concern. Studies in humans and animals indicate that ionizing radiation exposure to the eye produces characteristic lens changes, termed "radiation cataract," that can affect visual function. Animal models of radiation cataractogenesis have previously utilized inbred mouse or rat strains. These studies were essential for determining morphological changes and dose-response relationships between radiation exposure and cataract. However, the relevance of these studies to human radiosensitivity is limited by the narrow phenotypic range of genetically homogeneous animal models. To model radiation cataract in genetically diverse populations, longitudinal cataract phenotyping was nested within a lifetime carcinogenesis study in male and female heterogeneous stock (HS/Npt) mice exposed to 0.4 Gy HZE ions (n = 609) or 3.0 Gy γ-rays (n = 602) and in unirradiated controls (n = 603). Cataractous change was quantified in each eye for up to 2 years using Merriam-Focht grading criteria by dilated slit lamp examination. Virtual Optomotry™ measurement of visual acuity and contrast sensitivity was utilized to assess visual function in a subgroup of mice. Prevalence and severity of posterior lens opacifications were 2.6-fold higher in HZE ion and 2.3-fold higher in γ-ray irradiated mice compared to unirradiated controls. Male mice were at greater risk for spontaneous and radiation associated cataracts. Risk for cataractogenesis was associated with family structure, demonstrating that HS/Npt mice are well-suited to evaluate genetic determinants of ocular radiosensitivity. Last, mice were extensively evaluated for cataract and tumor formation, which revealed an overlap between individual susceptibility to both cancer and cataract.

Residential social vulnerability among healthcare personnel with and without severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection in Five US states, May-December 2020.

OBJECTIVE: To characterize residential social vulnerability among healthcare personnel (HCP) and evaluate its association with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection. DESIGN: Case-control study. SETTING: This study analyzed data collected in May-December 2020 through sentinel and population-based surveillance in healthcare facilities in Colorado, Minnesota, New Mexico, New York, and Oregon. PARTICIPANTS: Data from 2,168 HCP (1,571 cases and 597 controls from the same facilities) were analyzed. METHODS: HCP residential addresses were linked to the social vulnerability index (SVI) at the census tract level, which represents a ranking of community vulnerability to emergencies based on 15 US Census variables. The primary outcome was SARS-CoV-2 infection, confirmed by positive antigen or real-time reverse-transcriptase- polymerase chain reaction (RT-PCR) test on nasopharyngeal swab. Significant differences by SVI in participant characteristics were assessed using the Fisher exact test. Adjusted odds ratios (aOR) with 95% confidence intervals (CIs) for associations between case status and SVI, controlling for HCP role and patient care activities, were estimated using logistic regression. RESULTS: Significantly higher proportions of certified nursing assistants (48.0%) and medical assistants (44.1%) resided in high SVI census tracts, compared to registered nurses (15.9%) and physicians (11.6%). HCP cases were more likely than controls to live in high SVI census tracts (aOR, 1.76; 95% CI, 1.37-2.26). CONCLUSIONS: These findings suggest that residing in more socially vulnerable census tracts may be associated with SARS-CoV-2 infection risk among HCP and that residential vulnerability differs by HCP role. Efforts to safeguard the US healthcare workforce and advance health equity should address the social determinants that drive racial, ethnic, and socioeconomic health disparities.

Prevalence of COVID-19 Mitigation Behaviors in US Adults (August-December 2020): Nationwide Household Probability Survey.

BACKGROUND: COVID-19 mitigation behaviors, such as wearing masks, maintaining social distancing, and practicing hand hygiene, have been and will remain vital to slowing the pandemic. OBJECTIVE: This study aims to describe the period prevalence of consistent mask-wearing, social distancing, and hand hygiene practices during the peak of COVID-19 incidence (August-December 2020) and just before COVID-19 vaccine availability, overall and in demographic subgroups. METHODS: We used baseline survey data from a nationwide household probability sample to generate weighted estimates of mitigation behaviors: wearing masks, maintaining social distancing, and practicing hand hygiene. Weighted logistic regression explored differences in mitigation behaviors by demographics. Latent class analysis (LCA) identified patterns in mitigation behaviors. RESULTS: Among 4654 participants, most (n=2727, 58.6%) were female, were non-Hispanic White (n=3063, 65.8%), were aged 55 years or older (n=2099, 45.1%), lived in the South (n=2275, 48.9%), lived in metropolitan areas (n=4186, 89.9%), had at least a bachelor's degree (n=2547, 54.7%), had an income of US $50,000-$99,000 (n=1445, 31%), and were privately insured (n=2734, 58.7%). The period prevalence of consistent mask wearing was 71.1% (sample-weighted 95% CI 68.8-73.3); consistent social distancing, 42.9% (95% CI 40.5-45.3); frequent handwashing, 55.0% (95% CI 52.3-57.7); and frequent hand sanitizing, 21.5% (95% CI 19.4-23.8). Mitigation behaviors were more prevalent among women, older persons, Black or Hispanic persons, those who were not college graduates, and service-oriented workers. LCA identified an optimal-mitigation class that consistently practiced all behaviors (n=2656, 67% of US adults), a low-mitigation class that inconsistently practiced all behaviors (n=771, 20.6%), and a class that had optimal masking and social distancing but a high frequency of hand hygiene (n=463, 12.4%). CONCLUSIONS: Despite a high prevalence of COVID-19 mitigation behaviors, there were likely millions who did not consistently practice these behaviors during the time of the highest COVID-19 incidence. In future infectious disease outbreak responses, public health authorities should also consider addressing disparities in mitigation practices through more targeted prevention messaging.

Regulation of the hippocampal translatome by Apoer2-ICD release.

BACKGROUND: ApoE4, the most significant genetic risk factor for late-onset Alzheimer's disease (AD), sequesters a pro-synaptogenic Reelin receptor, Apoer2, in the endosomal compartment and prevents its normal recycling. In the adult brain, Reelin potentiates excitatory synapses and thereby protects against amyloid-ß toxicity. Recently, a gain-of-function mutation in Reelin that is protective against early-onset AD has been described. Alternative splicing of the Apoer2 intracellular domain (Apoer2-ICD) regulates Apoer2 signaling. Splicing of juxtamembraneous exon 16 alters the γ-secretase mediated release of the Apoer2-ICD as well as synapse number and LTP, and inclusion of exon 19 ameliorates behavioral deficits in an AD mouse model. The Apoer2-ICD has also been shown to alter transcription of synaptic genes. However, the role of Apoer2-ICD release upon transcriptional regulation and its role in AD pathogenesis is unknown. METHODS: To assess in vivo mRNA-primed ribosomes specifically in hippocampi transduced with Apoer2-ICD splice variants, we crossed wild-type, cKO, and Apoer2 cleavage-resistant mice to a Cre-inducible translating ribosome affinity purification (TRAP) model. This allowed us to perform RNA-Seq on ribosome-loaded mRNA harvested specifically from hippocampal cells transduced with Apoer2-ICDs. RESULTS: Across all conditions, we observed ~4,700 altered translating transcripts, several of which comprise key synaptic components such as extracellular matrix and focal adhesions with concomitant perturbation of critical signaling cascades, energy metabolism, translation, and apoptosis. We further demonstrated the ability of the Apoer2-ICD to rescue many of these altered transcripts, underscoring the importance of Apoer2 splicing in synaptic homeostasis. A variety of these altered genes have been implicated in AD, demonstrating how dysregulated Apoer2 splicing may contribute to neurodegeneration. CONCLUSIONS: Our findings demonstrate how alternative splicing of the APOE and Reelin receptor Apoer2 and release of the Apoer2-ICD regulates numerous translating transcripts in mouse hippocampi in vivo. These transcripts comprise a wide range of functions, and alterations in these transcripts suggest a mechanistic basis for the synaptic deficits seen in Apoer2 mutant mice and AD patients. Our findings, together with the recently reported AD-protective effects of a Reelin gain-of-function mutation in the presence of an early-onset AD mutation in Presenilin-1, implicate the Reelin/Apoer2 pathway as a target for AD therapeutics.

Variation in pediatric and adolescent electronic health data sharing practices under the 21st Century Cures Act.

OBJECTIVE: To describe real-world practices and variation in implementation of the Information Blocking provisions amongst healthcare organizations caring for pediatric patients. MATERIALS AND METHODS: An online survey regarding implementation practices was distributed to representatives from 10 participating US healthcare organizations located in 6 different states. The survey was followed by structured interviews conducted through video conference. Information was gathered about implementation practices at each organization, with a focus on patient and proxy portal access to, and segmentation capabilities of, certain data classes listed in the United States Core Data for Interoperability Version 1. RESULTS: All organizations had implemented the information blocking provisions at their institution. All organizations utilized different portal account types for proxies and users. All organizations reported the capability of sharing labs, medications, problem lists, imaging, and notes with the parent/guardian of the non-adolescent minor user with differences in how sensitive elements within the data classes were protected. Variability existed in how data was shared with the remaining user types. DISCUSSION: Significant variability exists in how organizations have implemented the information blocking rules. Variation in data sharing and data access between institutions can result in privacy breaches and create confusion about completeness of data for patients and families. CONCLUSION: Healthcare organizations have utilized varying strategies to comply with the information blocking provisions of the 21st Century Cures Act. Increased clarity from the Office of the National Coordinator for Health Information Technology on minor, adolescent, and caregiver privacy and improved segmentation capabilities from Electronic Health Record vendors is needed.

Apoer2-ICD-dependent regulation of hippocampal ribosome mRNA loading.

Background ApoE4, the most significant genetic risk factor for late-onset Alzheimer's disease (AD), sequesters a pro-synaptogenic Reelin receptor, Apoer2, in the endosomal compartment and prevents its normal recycling. In the adult brain, Reelin potentiates excitatory synapses and thereby protects against amyloid-ß toxicity. Recently, a gain-of-function mutation in Reelin that is protective against early-onset AD has been described. Alternative splicing of the Apoer2 intracellular domain (Apoer2-ICD) regulates Apoer2 signaling. Splicing of juxtamembraneous exon 16 alters the g-secretase mediated release of the Apoer2-ICD as well as synapse number and LTP, and inclusion of exon 19 ameliorates behavioral deficits in an AD mouse model. The Apoer2-ICD has also been shown to alter transcription of synaptic genes. However, the role of Apoer2 splicing for transcriptional regulation and its role in AD pathogenesis is unknown. Methods To assess in vivo mRNA-primed ribosomes specifically in hippocampi transduced with Apoer2-ICD splice variants, we crossed wild-type, cKO, and Apoer2 cleavage-resistant mice to a Cre-inducible translating ribosome affinity purification (TRAP) model. This allowed us to perform RNA-Seq on ribosome-loaded mRNA harvested specifically from hippocampal cells transduced with Apoer2-ICDs. Results Across all conditions, we observed ~ 4,700 altered ribosome-associated transcripts, several of which comprise key synaptic components such as extracellular matrix and focal adhesions with concomitant perturbation of critical signaling cascades, energy metabolism, translation, and apoptosis. We further demonstrated the ability of the Apoer2-ICD to rescue many of these altered transcripts, underscoring the importance of Apoer2 splicing in synaptic homeostasis. A variety of these altered genes have been implicated in AD, demonstrating how dysregulated Apoer2 splicing may contribute to neurodegeneration. Conclusions Our findings demonstrate how alternative splicing of the APOE and Reelin receptor Apoer2 and release of the Apoer2-ICD regulates numerous ribosome-associated transcripts in mouse hippocampi in vivo . These transcripts comprise a wide range of functions, and alterations in these transcripts suggest a mechanistic basis for the synaptic deficits seen in Apoer2 mutant mice and AD patients. Our findings, together with the recently reported AD-protective effects of a Reelin gain-of-function mutation in the presence of an early-onset AD mutation in Presenilin-1, implicate the Reelin/Apoer2 pathway as a target for AD therapeutics.

Effects of workplace stress, perceived stress, and burnout on collegiate coach mental health outcomes.

Introduction: Given the continuously changing job demands of coaches, coach burnout continues to be an important area of study. Coaching literature highlights the role occupational stressors play in the development and management of burnout. However, research highlights the potential need for the field to differentiate feelings of burnout from those of other sub-clinical mental health indicators (e.g., anxiety, depression). This study sought to examine the relationship between workplace stress, perceived stress, coach burnout, coach well-being, and sub-clinical health issues (anxiety, stress, depression). Methods: One hundred forty-four NCAA collegiate coaches completed online questionnaires measuring the proposed variables. Structural equation modeling was used to test the proposed hypothesis that burnout would serve as a partial mediator between workplace and perceived stress and mental health indicators (e.g., depression, anxiety, stress, and well-being). Results: Workplace stress and perceived stress were positively associated with both burnout subscales. Additionally, perceived stress alone exhibited a positive association with depression, anxiety, and stress and a negative association with well-being. While there was a positive significant relationship between disengagement and depression in the model and a negative significant relationship between disengagement and well-being, most relationships between the two burnout subscales and mental health outcomes were negligible. Discussion: It can be concluded that while workplace and perceived life stressors may impact feelings of burnout and mental health indicators directly, burnout does not appear to exhibit a strong effect on perceptions of mental health and well-being. In line with other research studies, it may be worth considering whether burnout should be considered another type of clinical mental health issue instead of as a direct contributor to coach mental health.

Cost-Effectiveness of Strategies to Identify Children with Perinatally Acquired Hepatitis C Infection.

OBJECTIVE: To determine the optimal testing strategy to identify children with perinatally acquired hepatitis C virus (HCV) infection. STUDY DESIGN: We used a decision-tree framework with a Markov disease progression model to conduct an economic analysis of 4 strategies, based on combinations of type and timing of test: anti-HCV with reflex to HCV RNA at 18 months among children known to be perinatally exposed (ie, baseline comparison strategy); HCV RNA testing at 2-6 months among infants known to be perinatally exposed (test strategy 1); universal anti-HCV with reflex to HCV RNA at 18 months among all children (test strategy 2); and universal HCV RNA testing at 2-6 months among all infants (test strategy 3). We estimated total cost, quality-adjusted life years, and disease sequalae for each strategy. RESULTS: Each of the 3 alternative testing strategies resulted in an increased number of children tested and improved health outcomes. HCV RNA testing at 2-6 months (test strategy 1) was cost-saving and resulted in a population-level difference in cost of $469 671. The 2 universal testing strategies resulted in an increase in quality-adjusted life years and an increase in total costs. CONCLUSIONS: Testing of perinatally exposed infants at age 2-6 months with a single HCV RNA test will reduce costs and improve health outcomes, preventing morbidity and mortality associated with complications from perinatal HCV infections.

Longitudinal Trends in Cardiovascular Risk Factor Profiles and Complications Among Patients Hospitalized for COVID-19 Infection: Results From the American Heart Association COVID-19 Cardiovascular Disease Registry.

BACKGROUND: The COVID-19 pandemic has evolved through multiple phases characterized by new viral variants, vaccine development, and changes in therapies. It is unknown whether rates of cardiovascular disease (CVD) risk factor profiles and complications have changed over time. METHODS: We analyzed the American Heart Association COVID-19 CVD registry, a national multicenter registry of hospitalized adults with active COVID-19 infection. The time period from April 2020 to December 2021 was divided into 3-month epochs, with March 2020 analyzed separately as a potential outlier. Participating centers varied over the study period. Trends in all-cause in-hospital mortality, CVD risk factors, and in-hospital CVD outcomes, including a composite primary outcome of cardiovascular death, cardiogenic shock, new heart failure, stroke, and myocardial infarction, were evaluated across time epochs. Risk-adjusted analyses were performed using generalized linear mixed-effects models. RESULTS: A total of 46 007 patient admissions from 134 hospitals were included (mean patient age 61.8 years, 53% male, 22% Black race). Patients admitted later in the pandemic were younger, more likely obese, and less likely to have existing CVD (Ptrend ≤0.001 for each). The incidence of the primary outcome increased from 7.0% in March 2020 to 9.8% in October to December 2021 (risk-adjusted Ptrend=0.006). This was driven by an increase in the diagnosis of myocardial infarction and stroke (Ptrend<0.0001 for each). The overall rate of in-hospital mortality was 14.2%, which declined over time (20.8% in March 2020 versus 10.8% in the last epoch; adjusted Ptrend<0.0001). When the analysis was restricted to July 2020 to December 2021, no temporal change in all-cause mortality was seen (adjusted Ptrend=0.63). CONCLUSIONS: Despite a shifting risk factor profile toward a younger population with lower rates of established CVD, the incidence of diagnosed cardiovascular complications of COVID increased from the onset of the pandemic through December 2021. All-cause mortality decreased during the initial months of the pandemic and thereafter remained consistently high through December 2021.

Estimating HIV Incident Diagnoses Among Men Who Have Sex With Men Eligible for Pre-exposure Prophylaxis but Not Taking It: Protocol and Feasibility Assessment of Data Sources and Methods.

BACKGROUND: HIV incidence estimates are published each year for all Ending the HIV Epidemic (EHE) counties, but they are not stratified by the demographic variables highly associated with risk of infection. Regularly updated estimates of HIV incident diagnoses available at local levels are required to monitor the epidemic in the United States over time and could contribute to background incidence rate estimates for alternative clinical trial designs for new HIV prevention products. OBJECTIVE: We describe methods using existing, robust data sources within areas in the United States to reliably estimate longitudinal HIV incident diagnoses stratified by race and age categories among men who have sex with other men (MSM) eligible for pre-exposure prophylaxis (PrEP) but not taking it. METHODS: This is a secondary analysis of existing data sources to develop new estimates of incident HIV diagnoses in MSM. We reviewed past methods used to estimate incident diagnoses and explored opportunities to improve these estimates. We will use existing surveillance data sources and population sizes of HIV PrEP-eligible MSM estimated from population-based data sources (eg, US Census data and pharmaceutical prescription databases) to develop metropolitan statistical area-level estimates of new HIV diagnoses among PrEP-eligible MSM. Required parameters are number of new diagnoses among MSM, estimates of MSM with an indication for PrEP, and prevalent PrEP use including median duration of use; these parameters will be stratified by jurisdiction and age group or race or ethnicity. Preliminary outputs will be available in 2023, and updated estimates will be produced annually thereafter. RESULTS: Data to parameterize new HIV diagnoses among PrEP-eligible MSM are available with varying levels of public availability and timeliness. In early 2023, the most recent available data on new HIV diagnoses were from the 2020 HIV surveillance report, which reports 30,689 new HIV infections in 2020, and 24,724 of them occurred in an MSA with a population of ≥500,000. Updated estimates for PrEP coverage based on commercial pharmacy claims data through February 2023 will be generated. The rate of new HIV diagnoses among MSM can be estimated from new diagnoses within each demographic group (numerator) and the total person-time at risk of diagnosis for each group (denominator) by metropolitan statistical area and year. To estimate time at risk, the person-time of individuals on PrEP or person-time after incident HIV infection but before diagnosis should be removed from stratified population size estimates of the total number of person-years with indications for PrEP. CONCLUSIONS: Reliable, serial, cross-sectional estimates for rates of new HIV diagnoses for MSM with PrEP indications can serve as benchmark community estimates of failures of HIV prevention and opportunities to improve services and will support public health epidemic monitoring and alternative clinical trial designs. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/42267.

A Mechanical Performance Study of Dual Cured Thermoset Resin Systems 3D-Printed with Continuous Carbon Fiber Reinforcement.

Additive manufacturing (AM) is one of the fastest-growing manufacturing technologies in modern times. One of the major challenges in the application of 3D-printed polymeric objects is expanding the applications to structural components, as they are often limited by their mechanical and thermal properties. To enhance the mechanical properties of 3D-printed thermoset polymer objects, reinforcing the polymer with continuous carbon fiber (CF) tow is an expanding direction of research and development. A 3D printer was constructed capable of printing with a continuous CF-reinforced dual curable thermoset resin system. Mechanical performance of the 3D-printed composites varied with the utilization of different resin chemistries. Three different commercially available violet light curable resins were mixed with a thermal initiator to improve curing by overcoming the shadowing effect of violet light by the CF. The resulting specimens' compositions were analyzed, and then the specimens were mechanically characterized for comparison in tensile and flexural performance. The 3D-printed composites' compositions were correlated to the printing parameters and resin characteristics. Slight enhancements in tensile and flexural properties from some commercially available resins over others appeared to be the result of better wet-out and adhesion.

Antibody induction in mice by liposome-displayed recombinant enterotoxigenic Escherichia coli (ETEC) colonization antigens.

BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) strains cause infectious diarrhea and colonize host intestine epithelia via surface-expressed colonization factors. Colonization factor antigen I (CFA/I), a prevalent ETEC colonization factor, is a vaccine target since antibodies directed to this fimbria can block ETEC adherence and prevent diarrhea. METHODS: Two recombinant antigens derived from CFA/I were investigated with a vaccine adjuvant system that displays soluble antigens on the surface of immunogenic liposomes. The first antigen, CfaEB, is a chimeric fusion protein comprising the minor (CfaE) and major (CfaB) subunits of CFA/I. The second, CfaEad, is the adhesin domain of CfaE. RESULTS: Owing to their His-tag, recombinant CfaEB and CfaEad, spontaneously bound upon admixture with nanoliposomes containing cobalt-porphyrin phospholipid (CoPoP), as well as a synthetic monophosphoryl lipid A (PHAD) adjuvant. Intramuscular immunization of mice with sub-microgram doses CfaEB or CfaEad admixed with CoPoP/PHAD liposomes elicited serum IgG and intestinal IgA antibodies. The smaller CfaEad antigen benefitted more from liposome display. Serum and intestine antibodies from mice immunized with liposome-displayed CfaEB or CfaEad recognized native CFA/I fimbria as evidenced by immunofluorescence and hemagglutination inhibition assays using the CFA/I-expressing H10407 ETEC strain. CONCLUSION: These data show that colonization factor-derived recombinant ETEC antigens exhibit immunogenicity when delivered in immunogenic particle-based formulations.