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Objective: We evaluate the feasibility and accuracy of existing point-of-care HIV tests performed by an untrained patient compared with the routinely used HIV point-of-care test offered to patients in 2 urban emergency departments (EDs).Methods: From April 2008 through December 2009, patients who had completed a standard HIV oral fluid test performed by a trained health care professional and who were unaware of their results were recruited to perform a rapid point-of-care HIV test. Patients were given a choice of the oral fluid or the fingerstick blood point-of-care test. Evaluation of acceptability to perform the mechanics of the test was accessed by questionnaire. For the "self-test," the participant obtained his or her own sample and performed the test. The patient's results were compared with standard oral fluid results obtained by the health care professional.Results: Overall, 478 of 564 (85%) patients receiving a standard oral fluid HIV test volunteered, with a mean age of 38 to 39 years. Ninety-one percent of participants chose oral fluid and 9% chose blood (P<.05). Self-test results were 99.6% concordant with health care professionals' test results. For the self-testers, 94% of oral fluid testers and 84.4% of blood testers reported trusting the self-administered test result "very much." Furthermore, 95.6% of the oral fluid group and 93.3% of the blood group would "probably" or "definitely" perform a test at home, if available.Conclusion: This study demonstrated that a significant proportion of patients offered a self-HIV point-of-care test volunteered and preferred using oral fluid. Patients' results agreed with standard HIV point-of-care results. The majority of participants trusted their results and would perform a point-of-care HIV test at home, given the opportunity. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Understanding perceived benefits and disadvantages of HIV testing in emergency departments (EDs) is imperative to overcoming barriers to implementation. We codify those domains of public health and clinical care most affected by implementing HIV testing in EDs, as determined by expert opinion. METHODS: Opinions were systematically collected from attendees of the 2007 National ED HIV Testing Consortium meeting. Structured evaluation of strengths, weaknesses, opportunities, and threats analysis was conducted to assess the impact of ED-based HIV testing on public health. A modified Delphi method was used to assess the impact of ED-based HIV testing on clinical care from both individual patient and individual provider perspectives. RESULTS: Opinions were provided by 98 experts representing 42 academic and nonacademic institutions. Factors most frequently perceived to affect public health were (strengths) high volume of ED visits and high prevalence of HIV, (weaknesses) undue burden on EDs, (opportunities) reduction of HIV stigma, and (threats) lack of resources in EDs. Diagnostic testing and screening for HIV were considered to have a favorable impact on ED clinical care from both individual patient and individual provider perspectives; however, negative test results were not perceived to have any benefit from the provider's perspective. The need for HIV counseling in the ED was considered to have a negative impact on clinical care from the provider's perspective. CONCLUSION: Experts in ED-based HIV testing perceived expanded ED HIV testing to have beneficial impacts for both the public health and individual clinical care; however, limited resources were frequently cited as a possible impediment. Many issues must be resolved through further study, education, and policy changes if the full potential of HIV testing in EDs is to be realized. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess emergency physicians' diagnostic approach to the patient with dizziness, using a multicenter quantitative survey. PARTICIPANTS AND METHODS: We anonymously surveyed attending and resident emergency physicians at 17 academic-affiliated emergency departments with an Internet-based survey (September 1, 2006, to November 3, 2006). The survey respondents ranked the relative importance of symptom quality, timing, triggers, and associated symptoms and indicated their agreement with 20 statements about diagnostic assessment of dizziness (Likert scale). We used logistic regression to assess the impact of 'symptom quality ranked first' on odds of agreement with diagnostic statements; we then stratified responses by academic rank. RESULTS: Of the 505 individuals surveyed, 415 responded for an overall response rate of 82%. A total of 93% (95% confidence interval [CI], 90%-95%) agreed that determining type of dizziness is very important, and 64% (95% CI, 60%-69%) ranked symptom quality as the most important diagnostic feature. In a multivariate model, those ranking quality first (particularly resident physicians) more often reported high-risk reasoning that might predispose patients to misdiagnosis (eg, in a patient with persistent, continuous dizziness, who could have a cerebellar stroke, resident physicians reported feeling reassured that a normal head computed tomogram indicates that the patient can safely go home) (odds ratio, 6.74; 95% CI, 2.05-22.19). CONCLUSION: Physicians report taking a quality-of-symptoms approach to the diagnosis of dizziness in patients in the emergency department. Those relying heavily on this approach may be predisposed to high-risk downstream diagnostic reasoning. Other clinical features (eg, timing, triggers, associated symptoms) appear relatively undervalued. Educational initiatives merit consideration. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To quantify precision in patient reports of different attributes of dizziness. PATIENTS AND METHODS: In a cross-sectional study, we interviewed consecutive adult patients with dizziness at 2 urban academic emergency departments (EDs) from July 2, 2005, to August 26, 2005. We excluded patients who were too sick for an interview or who posed a risk to the interviewer. We included those who were 'dizzy, light-headed, or off-balance' for 7 days or less or previously 'bothered' by the same conditions. We assessed descriptions of dizziness quality elicited by 4 questions in different formats (open-ended, multiresponse, single-choice, and directed). Clarity was assessed qualitatively (vague, circular) and quantitatively (overlap of types of dizziness). Consistency was measured by frequency of mismatched responses across question formats. Reliability was determined by test-retest. RESULTS: Of 1,342 patients screened, 872 (65%) were dizzy, light-headed, or off-balance in the past 7 days (n=677) or previously bothered by dizziness (n=195). Among these 872 patients with dizziness, 44% considered dizziness 'the main reason' or 'part of the reason' for the ED visit. Open-ended descriptions were frequently vague or circular. A total of 62% selected more than 1 dizziness type on the multiresponse question. On the same question, 54% did not pick 1 or more types endorsed previously in open description. Of 218 patients not identifying vertigo, spinning, or motion on the first 3 questions, 70% confirmed 'spinning or motion' on directed questioning. Asked to choose the single best descriptor, 52% picked a different response on retest approximately 6 minutes later. By comparison, reports of dizziness duration and triggers were clear, consistent, and reliable. CONCLUSION: Descriptions of the quality of dizziness are unclear, inconsistent, and unreliable, casting doubt on the validity of the traditional approach to the patient with dizziness. Alternative approaches, emphasizing timing and triggers over type, should be investigated. [ABSTRACT FROM AUTHOR]

Background: Despite many studies evaluating lung ultrasound (LUS) for coronavirus disease 2019 (COVID-19) prognostication, the generalizability and utility across clinical settings are uncertain., Methods: Adults (≥18 years of age) with COVID-19 were enrolled at 2 military hospitals, an emergency department, home visits, and a homeless shelter in the United States, and in a referral hospital in Uganda. Participants had a 12-zone LUS scan performed at time of enrollment and clips were read off-site. The primary outcome was progression to higher level of care after the ultrasound scan. We calculated the cross-validated area under the curve for the validation cohort for individual LUS features., Results: We enrolled 191 participants with COVID-19 (57.9% female; median age, 45.0 years [interquartile range, 31.5-58.0 years]). Nine participants clinically deteriorated. The top predictors of worsening disease in the validation cohort measured by cross-validated area under the curve were B-lines (0.88 [95% confidence interval {CI}, .87-.90]), discrete B-lines (0.87 [95% CI, .85-.88]), oxygen saturation (0.82 [95%, CI, .81-.84]), and A-lines (0.80 [95% CI, .78-.81])., Conclusions: In an international multisite point-of-care ultrasound cohort, LUS parameters had high discriminative accuracy. Ultrasound can be applied toward triage across a wide breadth of care settings during a pandemic., Competing Interests: Potential conflicts of interest. S. D. P. reports that the USUHS IDCRP, a US DOD institution, and HJF were funded under a cooperative research and development agreement to conduct an unrelated phase 3 COVID-19 monoclonal antibody immunoprophylaxis trial sponsored by AstraZeneca. The HJF, in support of the USUHS IDCRP, was funded by the DOD Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense to augment the conduct of an unrelated phase 3 vaccine trial sponsored by AstraZeneca. Both of these trials were part of the US government COVID-19 response. Neither is related to the work presented here. T.S. receives consulting feeds from Verona Pharmaceuticals, Apogee Therapeutics, and honoraraia from American Thoracic Society and the COPD foundation. T.S. is an advisor to 4D Medical. C.C. receives consulting fees from Johnson & Johnson and Bayer AG regarding unrelated wearable devices. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background/Objective: SeptiCyte RAPID is a transcriptional host response assay that discriminates between sepsis and non-infectious systemic inflammation (SIRS) with a one-hour turnaround time. The overall performance of this test in a cohort of 419 patients has recently been described [Balk et al., J Clin Med 2024, 13, 1194]. In this study, we present the results from a detailed stratification analysis in which SeptiCyte RAPID performance was evaluated in the same cohort across patient groups and subgroups encompassing different demographics, comorbidities and disease, sources and types of pathogens, interventional treatments, and clinically defined phenotypes. The aims were to identify variables that might affect the ability of SeptiCyte RAPID to discriminate between sepsis and SIRS and to determine if any patient subgroups appeared to present a diagnostic challenge for the test. Methods: (1) Subgroup analysis, with subgroups defined by individual demographic or clinical variables, using conventional statistical comparison tests. (2) Principal component analysis and k-means clustering analysis to investigate phenotypic subgroups defined by unique combinations of demographic and clinical variables. Results: No significant differences in SeptiCyte RAPID performance were observed between most groups and subgroups. One notable exception involved an enhanced SeptiCyte RAPID performance for a phenotypic subgroup defined by a combination of clinical variables suggesting a septic shock response. Conclusions: We conclude that for this patient cohort, SeptiCyte RAPID performance was largely unaffected by key variables associated with heterogeneity in patients suspected of sepsis.

Background: Point-of-care (POC) tests for sexually transmitted infections (STIs) permit delivery of results during the patient's emergency department (ED) encounter. We evaluated performance, patient acceptability, and feasibility of a new duplex POC test, Chembio Dual Path Platform HIV-Syphilis Assay, in an urban ED setting., Methods: Convenience sampling approach prioritizing those considered at increased risk for an STI and/or with a history of HIV. For the performance evaluation, participants were tested for HIV/syphilis with the Chembio POC assay and the reference laboratory tests; sensitivity and specificity were determined. For the patient acceptability evaluation, participants completed pre- and post-user surveys. For the feasibility evaluation, ED clinical technicians completed a survey evaluating their perceptions regarding feasibility of use of this POC test., Results: A total of 327 patients were consented and enrolled. The diagnostic sensitivity and specificity of the Chembio POC assay for HIV were 96.5% (95% confidence interval [CI], 90.1%-99.3%) and 99.6% (95% CI, 97.7%-100.0%), respectively, and for syphilis, the values were 93.9% (95% CI, 85.0%-98.3%) and 99.6% (95% CI, 97.9%-100.0%), respectively. Regarding patient acceptability, 87% trusted the result, and 93% reported that they were more likely to seek treatment if they received a positive STI test result in the ED rather than after the ED visit. Regarding feasibility, 90% of the technicians reported that they would recommend using the test in EDs., Conclusions: The Chembio Dual Path Platform HIV-Syphilis POC Assay had excellent performance characteristics when evaluated in an ED population, as well as high perceived acceptability from patients, and feasibility for ED use from clinical technicians. The test may have utility for HIV-syphilis screening among high-risk ED patients., Competing Interests: Conflict of Interest and Sources of Funding: The authors have no conflicts of interest to declare. This study was funded by U54EB007958, National Institute of Biomedical Imagining and Bioengineering, National Institutes of Health. Chembio Diagnostic Systems provided diagnostic test kits., (Copyright © 2024 American Sexually Transmitted Diseases Association. All rights reserved.)

Influenza, a human disease caused by viruses in the Orthomyxoviridae family, is estimated to infect 5% -10 % of adults and 20% -30 % of children annually. Influenza A (IAV) and Influenza B (IBV) viruses accumulate amino acid substitutions (AAS) in the hemagglutinin (HA) and neuraminidase (NA) proteins seasonally. These changes, as well as the dominating viral subtypes, vary depending on geographical location, which may impact disease prevalence and the severity of the season. Genomic surveillance is crucial for capturing circulation patterns and characterizing AAS that may affect disease outcomes, vaccine efficacy, or antiviral drug activities. In this study, whole-genome sequencing of IAV and IBV was attempted on positive remnant clinical samples (587) collected from 580 patients between June 2023 and February 2024 in the Johns Hopkins Health System (JHHS). Full-length HA segments were obtained from 424 (72.2 %) samples. H1N1pdm09 (71.7 %) was the predominant IAV subtype, followed by H3N2 (16.7 %) and IBV-Victoria clade V1A.3a.2 (11.6 %). Within H1N1pdm09 HA sequences, the 6B1A.5a.2a.1 (60.5 %) clade was the most represented. Full-length NA segments were obtained from 421 (71.7 %) samples. Within H1N1pdm09 and IBV, AAS previously proposed to change susceptibility to NA inhibitors were infrequently detected. Phylogeny of HA and NA demonstrated heterogeneous HA and NA H1N1pdm09 and IBV subclades. No significant differences were observed in admission rates or use of supplemental oxygen between different subtypes or clades. Influenza virus genomic surveillance is essential for understanding the seasonal evolution of influenza viruses and their association with disease prevalence and outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: HHM reports research collaborations with Bio-Rad, Qiagen, DiaSorin, and Hologic, received honoraria from BD diagnostics and Bio-Rad, and serves on the advisory board for Seegene., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Study Objective: Identification of HIV remains a critical health priority for which emergency departments (EDs) are a central focus. The comparative cost-effectiveness of various HIV screening strategies in EDs remains largely unknown. The goal of this study was to compare programmatic costs and cost-effectiveness of nontargeted and 2 forms of targeted opt-out HIV screening in EDs using results from a multicenter, pragmatic randomized clinical trial., Methods: This economic evaluation was nested in the HIV Testing Using Enhanced Screening Techniques in Emergency Departments (TESTED) trial, a multicenter pragmatic clinical trial of different ED-based HIV screening strategies conducted from April 2014 through January 2016. Patients aged 16 years or older, with normal mental status and not critically ill, or not known to be living with HIV were randomized to 1 of 3 HIV opt-out screening approaches, including nontargeted, enhanced targeted, or traditional targeted, across 4 urban EDs in the United States. Each screening method was fully integrated into routine emergency care. Direct programmatic costs were determined using actual trial results, and time-motion assessment was used to estimate personnel activity costs. The primary outcome was newly diagnosed HIV. Total annualized ED programmatic costs by screening approach were calculated using dollars adjusted to 2023 as were costs per patient newly diagnosed with HIV. One-way and multiway sensitivity analyses were performed., Results: The trial randomized 76,561 patient visits, resulting in 14,405 completed HIV tests, and 24 (0.2%) new diagnoses. Total annualized new diagnoses were 12.9, and total annualized costs for nontargeted, enhanced targeted, and traditional targeted screening were $111,861, $88,629, and $70,599, respectively. Within screening methods, costs per new HIV diagnoses were $20,809, $23,554, and $18,762, respectively. Enhanced targeted screening incurred higher costs but with similar annualized new cases detected compared with traditional targeted screening. Nontargeted screening yielded an incremental cost-effectiveness ratio of $25,586 when compared with traditional targeted screening. Results were most sensitive to HIV prevalence and costs of HIV tests., Conclusion: Nontargeted HIV screening was more costly than targeted screening largely due to an increased number of HIV tests performed. Each HIV screening strategy had similar within-strategy costs per new HIV diagnosis with traditional targeted screening yielding the lowest cost per new diagnosis. For settings with budget constraints or very low HIV prevalences, the traditional targeted approach may be preferred; however, given only a slightly higher cost per new HIV diagnosis, ED settings looking to detect the most new cases may prefer nontargeted screening., (Copyright © 2024 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Background: During the 2017-18 influenza season in the USA, there was a high incidence of influenza illness and mortality. However, no apparent antigenic change was identified in the dominant H3N2 viruses, and the severity of the season could not be solely attributed to a vaccine mismatch. We aimed to investigate whether the altered virus properties resulting from gene reassortment were underlying causes of the increased case number and disease severity associated with the 2017-18 influenza season., Methods: Samples included were collected from patients with influenza who were prospectively recruited during the 2016-17 and 2017-18 influenza seasons at the Johns Hopkins Hospital Emergency Departments in Baltimore, MD, USA, as well as from archived samples from Johns Hopkins Health System sites. Among 647 recruited patients with influenza A virus infection, 411 patients with whole-genome sequences were available in the Johns Hopkins Center of Excellence for Influenza Research and Surveillance network during the 2016-17 and 2017-18 seasons. Phylogenetic trees were constructed based on viral whole-genome sequences. Representative viral isolates of the two seasons were characterised in immortalised cell lines and human nasal epithelial cell cultures, and patients' demographic data and clinical outcomes were analysed., Findings: Unique H3N2 reassortment events were observed, resulting in two predominant strains in the 2017-18 season: HA clade 3C.2a2 and clade 3C.3a, which had novel gene segment constellations containing gene segments from HA clade 3C.2a1 viruses. The reassortant re3C.2a2 viruses replicated with faster kinetics and to a higher peak titre compared with the parental 3C.2a2 and 3C.2a1 viruses (48 h vs 72 h). Furthermore, patients infected with reassortant 3C.2a2 viruses had higher Influenza Severity Scores than patients infected with the parental 3C.2a2 viruses (median 3·00 [IQR 1·00-4·00] vs 1·50 [1·00-2·00]; p=0·018)., Interpretation: Our findings suggest that the increased severity of the 2017-18 influenza season was due in part to two intrasubtypes, cocirculating H3N2 reassortant viruses with fitness advantages over the parental viruses. This information could help inform future vaccine development and public health policies., Funding: The Center of Excellence for Influenza Research and Response in the US, National Science and Technology Council, and Chang Gung Memorial Hospital in Taiwan., Competing Interests: Declaration of interests SV owns stock in VIR Biotechnology as an employee of the company, unrelated to the submitted work. The other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Although they face higher occupational risk of contracting viral respiratory infections, hospital healthcare worker vaccine hesitancy persists. While most studies have used survey methods to quantify the prevalence of and reasons for healthcare worker vaccine hesitancy, this study employs a qualitative approach to understand their attitudes and beliefs associated with influenza and COVID-19 vaccination., Methods: To understand frontline healthcare worker experiences and perspectives on influenza and COVID-19 vaccination, 30 semi-structured interviews were conducted in summer/fall 2022 with staff recruited from two Johns Hopkins hospitals in Maryland. An in-depth, key informant interview was conducted with an expert in public health audience engagement. Interviews were audio recorded and transcribed for thematic and Framework analysis using NVivo software (QSR International, Melbourne, Australia)., Results: Healthcare workers engaged in little influenza vaccine information seeking due to their familiarity with the disease and low perceived disease severity. Approximately half (n=16) of healthcare workers reported no vaccine hesitancy towards influenza or COVID-19 vaccines. No physicians or physician assistants expressed any vaccine hesitancy, while most nurses expressed some (n=10). More than half of the women (n=14) expressed COVID-19 vaccine hesitancy compared to none of the men. Structural factors including hospital tier, unit assignment, and professional role influenced perceived risk of disease exposure and subsequent healthcare worker vaccination decisions. Institutional policies, including mandates and a pro-vaccine environment encouraged vaccination uptake. Healthcare workers reported being more receptive to vaccine messaging that focused on protection from disease, scientific and public health data and their heightened occupational exposure to pathogens., Conclusions: Despite their medical knowledge, healthcare workers are susceptible to vaccine hesitancy. Strategies to address specific concerns are needed and can be informed by our findings. A flexible and multi-pronged approach that considers individual anxieties, workplace structures, and the need for open communication with tailored messaging is necessary to promote vaccine acceptance in healthcare settings., Key Messages: What is already known on this topic: Healthcare worker vaccine hesitancy has been associated with many factors including race, gender, age and concerns about vaccine safety. What this study adds: Much of the research on healthcare worker vaccine hesitancy has used surveys and questionnaires giving a broad description of the prevalence and patterns of vaccine hesitancy in the healthcare workforce. This qualitative study examines vaccine behavior (rather than merely intent) through a cross comparison of healthcare workers' experiences and attitudes towards influenza and COVID-19 vaccination. How this study might affect research, practice or policy: Study findings can be used to help tailor vaccine messaging to hospital healthcare workers which could offset concerns regarding vaccine efficacy and risk, to promote vaccine uptake.

Introduction: Active and passive surveillance studies have found that a greater proportion of females report adverse events (AE) following receipt of either the COVID-19 or seasonal influenza vaccine compared to males. In a predominately young adult female population of healthcare workers, we sought to determine the intersection of biological sex and sociocultural gender differences in prospective active reporting of vaccine outcomes, which remains poorly characterized., Methods: This cohort study enrolled Johns Hopkins Health System healthcare workers (HCWs) who were recruited from the mandatory annual fall 2019-2022 influenza vaccine and the fall 2022 COVID-19 bivalent vaccine campaigns. Vaccine recipients were enrolled the day of vaccination and AE surveys were administered two days post-vaccination for bivalent COVID-19 and influenza vaccine recipients. Data were collected regarding the presence of a series of solicited local and systemic AEs. Open-ended answers about participants' experiences with AEs also were collected for the COVID-19 vaccine recipients., Results: Females were more likely to report local AEs after either influenza (OR = 2.28, p = 0.001) or COVID-19 (OR = 2.57, p = 0.008) vaccination compared to males, regardless of age or race. Males and females had comparable probabilities of reporting systemic AEs after either influenza (OR = 1.18, p = 0.552) or COVID-19 (OR = 0.96, p = 0.907) vaccination. Hormonal birth control use did not impact the rates of reported AEs following influenza vaccination among reproductive-aged female HCWs. Women reported more interruptions in their daily routine following COVID-19 vaccination than men and were more likely to seek out self-treatment. More women than men scheduled their COVID-19 vaccination before their days off in anticipation of AEs., Conclusions: Our findings highlight the need for sex- and gender-inclusive policies to inform more effective mandatory occupational health vaccination strategies. Further research is needed to evaluate the potential disruption of AEs on occupational responsibilities following mandated vaccination for healthcare workers, a predominately female population, and to more fully characterize the post-vaccination behavioral differences between men and women., (© 2024. The Author(s).)

Background: Syphilis diagnosis in the emergency department (ED) setting is often missed due to the lack of ED-specific testing strategies. We characterized ED patients with high-titer syphilis infections (HTSIs) with the goal of defining a screening strategy that most parsimoniously identifies undiagnosed, untreated syphilis infections., Methods: Unlinked, de-identified remnant serum samples from patients attending an urban ED, between 10 January and 9 February 2022, were tested using a three-tier testing algorithm, and sociodemographic variables were extracted from ED administrative database prior to testing. Patients who tested positive for treponemal antibodies in the first tier and positive at high titer (≥1:8) for nontreponemal antibodies in the second tier were classified as HTSI. Human immunodeficiency virus (HIV) status was determined with Bio-Rad enzyme-linked immunosorbent assay and confirmatory assays. Exact logistic regression and classification and regression tree (CART) analyses were performed to determine factors associated with HTSI and derive screening strategies., Results: Among 1951 unique patients tested, 23 (1.2% [95% confidence interval, .8%-1.8%]) had HTSI. Of those, 18 (78%) lacked a primary care physician, 5 (22%) were HIV positive, and 8 (35%) were women of reproductive age (18-49 years). CART analysis (area under the curve of 0.67) showed that using a screening strategy that measured syphilis antibodies in patients with HIV, without a primary care physician, and women of reproductive age would have identified most patients with HTSI (21/23 [91%])., Conclusions: We show a high prevalence of HTSI in an urban ED and propose a feasible, novel screening strategy to curtail community transmission and prevent long-term complications., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: To determine the diagnostic accuracy of a rapid host-protein test for differentiating bacterial from viral infections in patients who presented to the emergency department (ED) or urgent care center (UCC)., Methods: This was a prospective multicenter, blinded study. MeMed BV (MMBV), a test based on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-inducible protein-10 (IP-10), and C-reactive protein (CRP), was measured using a rapid measurement platform. Patients were enrolled from 9 EDs and 3 UCCs in the United States and Israel. Patients >3 months of age presenting with fever and clinical suspicion of acute infection were considered eligible. MMBV results were not provided to the treating clinician. MMBV results (bacterial/viral/equivocal) were compared against a reference standard method for classification of infection etiology determined by expert panel adjudication. Experts were blinded to MMBV results. They were provided with comprehensive patient data, including laboratory, microbiological, radiological and follow-up., Results: Of 563 adults and children enrolled, 476 comprised the study population (314 adults, 162 children). The predominant clinical syndrome was respiratory tract infection (60.5% upper, 11.3% lower). MMBV demonstrated sensitivity of 90.0% (95% confidence interval [CI]: 80.3-99.7), specificity of 92.8% (90.0%-95.5%), and negative predictive value of 98.8% (96.8%-99.6%) for bacterial infections. Only 7.2% of cases yielded equivocal MMBV scores. Area under the curve for MMBV was 0.95 (0.90-0.99)., Conclusions: MMBV had a high sensitivity and specificity relative to reference standard for differentiating bacterial from viral infections. Future implementation of MMBV for patients with suspected acute infections could potentially aid with appropriate antibiotic decision-making., Competing Interests: Cesar A. Arias, Natasha Ballard, Karen C. Carroll, Andrea T. Cruz, Richard Gordon, Salim Halabi, Jeffrey D. Harris, Kristina G. Hulten, Theresa Jacob, Mark D. Kellogg, Adi Klein, Pninit Shaked Mishan, Sergey M. Motov, Octavia M. Peck‐Palmer, Leticia M. Ryan, Ma'anit Shapira, George S. Suits, Henry E. Wang, Alexandra Weissman, and Richard E. Rothman have no relevant conflict of interests to declare. Richard G. Bachur and Sheldon L. Kaplan participated in a scientific advisory board on health economic modeling for MeMed and were compensated for their time. Richard E. Rothman participated in a scientific board on health care economic modeling (without compensation). Richard G. Bachur, Sheldon L. Kaplan, and Richard E. Rothman participated in discussions with the U.S. Food and Drug Administration clearance and were involved in study design, patient recruitment, data collection and analysis, and drafting and revising the manuscript., (© 2024 The Authors. Journal of the American College of Emergency Physicians Open published by Wiley Periodicals LLC on behalf of American College of Emergency Physicians.)

Background: Bivalent mRNA vaccines were recommended since September 2022. However, coverage with a recent vaccine dose has been limited, and there are few robust estimates of bivalent VE against symptomatic SARS-CoV-2 infection (COVID-19). We estimated VE of a bivalent mRNA vaccine dose against COVID-19 among eligible U.S. healthcare personnel who had previously received monovalent mRNA vaccine doses., Methods: We conducted a case-control study in 22 U.S. states, and enrolled healthcare personnel with COVID-19 (case-participants) or without COVID-19 (control-participants) during September 2022-May 2023. Participants were considered eligible for a bivalent mRNA dose if they had received 2-4 monovalent (ancestral-strain) mRNA vaccine doses, and were ≥67 days after the most recent vaccine dose. We estimated VE of a bivalent mRNA dose using conditional logistic regression, accounting for matching by region and four-week calendar period. We adjusted estimates for age group, sex, race and ethnicity, educational level, underlying health conditions, community COVID-19 exposure, prior SARS-CoV-2 infection, and days since the last monovalent mRNA dose., Results: Among 3,647 healthcare personnel, 1,528 were included as case-participants and 2,119 as control-participants. Participants received their last monovalent mRNA dose a median of 404 days previously; 1,234 (33.8%) also received a bivalent mRNA dose a median of 93 days previously. Overall, VE of a bivalent dose was 34.1% (95% CI, 22.6%-43.9%) against COVID-19 and was similar by product, days since last monovalent dose, number of prior doses, age group, and presence of underlying health conditions. However, VE declined from 54.8% (95% CI, 40.7%-65.6%) after 7-59 days to 21.6% (95% CI 5.6%-34.9%) after ≥60 days., Conclusions: Bivalent mRNA COVID-19 vaccines initially conferred approximately 55% protection against COVID-19 among U.S. healthcare personnel. However, protection waned after two months. These findings indicate moderate initial protection against symptomatic SARS-CoV-2 infection by remaining up-to-date with COVID-19 vaccines., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Monica Brackney owned stock in Moderna from November 2022–April 2023 stock as part of portfolio managed by Parametric Investments Portfolio LLC. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.]., (Published by Elsevier Ltd.)

Objective: Sepsis is a leading cause of mortality. Predicting outcomes is challenging and few biomarkers perform well. Defects in the renin-angiotensin system (RAS) can predict clinical outcomes in sepsis and may outperform traditional biomarkers. We postulated that RAS dysfunction (elevated active renin, angiotensin 1-7 [Ang-(1-7)], and angiotensin-converting enzyme 2 (ACE2) activity with depressed Ang-II and ACE activity) would be associated with mortality in a cohort of septic patients., Design: Post hoc analysis of patients enrolled in the Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) randomized controlled trial., Setting: Forty-three hospitals across the United States., Patients: Biorepository samples of 103 patients., Interventions: We analyzed day 0 (within 24 hr of respiratory failure, septic shock, or both) and day 3 samples ( n = 103 and 95, respectively) for assessment of the RAS. The association of RAS values with 30-day mortality was determined using Cox proportional hazards regression with multivariable adjustments for age, sex, VICTAS treatment arm, systolic blood pressure, Sequential Organ Failure Assessment Score, and vasopressor use., Measurements and Main Results: High baseline active renin values were associated with higher 30-day mortality when dichotomized to the median of 188.7 pg/mL (hazard ratio [HR] = 2.84 [95% CI, 1.10-7.33], p = 0.031) or stratified into quartiles (Q1 = ref, HR Q2 = 2.01 [0.37-11.04], HR Q3 = 3.22 [0.64-16.28], HR Q4 = 5.58 [1.18-26.32], p for linear trend = 0.023). A 1- sd (593.6 pg/mL) increase in renin from day 0 to day 3 was associated with increased mortality (HR = 3.75 [95% CI, 1.94-7.22], p < 0.001), and patients whose renin decreased had improved survival compared with those whose renin increased (HR 0.22 [95% CI, 0.08-0.60], p = 0.003). Ang-(1-7), ACE2 activity, Ang-II and ACE activity did not show this association. Mortality was attenuated in patients with renin over the median on day 0 who received the VICTAS intervention, but not on day 3 ( p interaction 0.020 and 0.137, respectively). There were no additional consistent patterns of mortality on the RAS from the VICTAS intervention., Conclusions: Baseline serum active renin levels were strongly associated with mortality in critically ill patients with sepsis. Furthermore, a greater relative activation in circulating renin from day 0 to day 3 was associated with a higher risk of death., Competing Interests: Dr. Schaich received funding from the National Institute on Aging (K01AG073581) and an internal institutional pilot grant. Dr. Chappell’s institution received funding from the National Heart, Lung, and Blood Institute (R01HL146818); he received support for article research from the National Institutes of Health (NIH). Dr. McCurdy’s institution received funding from the Maryland Innovation Initiative; he disclosed he is chief medical officer for BOA Biomedical. Drs. Sevransky, Rothman, and Wright’s institutions received funding from the Marcus Foundation. Dr. Sevransky’s institution received funding from the Centers for Disease Control and Prevention and the Department of Health and Human Services; He disclosed he is an associate editor for Critical Care Medicine. Dr. Rothman disclosed use of Vit C, thiamine and steroid for treatment of sepsis. Dr. Wright’s institution received funding from the NIH; he received funding from the Neurotrauma Sciences Advisory Board and Astrocyte Pharma; he disclosed he was an expert witness for multiple different legal firms; he received support for article research from the Marcus Foundation. Dr. Khanna received grant funding from Hypertension and Vascular Research Center at the Wake Forest University School of Medicine (AG073581) to study mechanisms of renin dysregulation in shock. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

(1) Background: SeptiCyte RAPID is a molecular test for discriminating sepsis from non-infectious systemic inflammation, and for estimating sepsis probabilities. The objective of this study was the clinical validation of SeptiCyte RAPID, based on testing retrospectively banked and prospectively collected patient samples. (2) Methods: The cartridge-based SeptiCyte RAPID test accepts a PAXgene blood RNA sample and provides sample-to-answer processing in ~1 h. The test output (SeptiScore, range 0-15) falls into four interpretation bands, with higher scores indicating higher probabilities of sepsis. Retrospective (N = 356) and prospective (N = 63) samples were tested from adult patients in ICU who either had the systemic inflammatory response syndrome (SIRS), or were suspected of having/diagnosed with sepsis. Patients were clinically evaluated by a panel of three expert physicians blinded to the SeptiCyte test results. Results were interpreted under either the Sepsis-2 or Sepsis-3 framework. (3) Results: Under the Sepsis-2 framework, SeptiCyte RAPID performance for the combined retrospective and prospective cohorts had Areas Under the ROC Curve (AUCs) ranging from 0.82 to 0.85, a negative predictive value of 0.91 (sensitivity 0.94) for SeptiScore Band 1 (score range 0.1-5.0; lowest risk of sepsis), and a positive predictive value of 0.81 (specificity 0.90) for SeptiScore Band 4 (score range 7.4-15; highest risk of sepsis). Performance estimates for the prospective cohort ranged from AUC 0.86-0.95. For physician-adjudicated sepsis cases that were blood culture (+) or blood, urine culture (+)(+), 43/48 (90%) of SeptiCyte scores fell in Bands 3 or 4. In multivariable analysis with up to 14 additional clinical variables, SeptiScore was the most important variable for sepsis diagnosis. A comparable performance was obtained for the majority of patients reanalyzed under the Sepsis-3 definition, although a subgroup of 16 patients was identified that was called septic under Sepsis-2 but not under Sepsis-3. (4) Conclusions: This study validates SeptiCyte RAPID for estimating sepsis probability, under both the Sepsis-2 and Sepsis-3 frameworks, for hospitalized patients on their first day of ICU admission.

Potentially septic patients have a huge clinical and economic impact on hospitals and often present to the emergency department (ED) with undifferentiated symptoms. The triage of these patients is complex and has historically relied heavily upon provider judgment. This study aims to evaluate the consistency of provider judgment and the potential of a new host response sepsis test to aid in the triage process. A modified Delphi study involving 26 participants from multiple specialties was conducted to evaluate provider agreement about sepsis risk and to test proposed actions based on the results of a sepsis test. The participants considered case vignettes of potentially septic patients designed to represent diagnostic dilemmas. Provider assessment of sepsis risk in these cases ranged from 10% to 90% and agreement was poor. Agreement about clinical actions to take in response to testing improved when participants considered their own hypothetical borderline cases. New host response testing for sepsis may have the potential to improve sepsis diagnosis and care and should be applied in a protocolized fashion to ensure consistency of results.

Background: The circulation and the genomic evolution of influenza A(H3N2) viruses during the 2021/2022 and 2022/2023 seasons were studied and associated with infection outcomes., Methods: Remnant influenza A-positive samples following standard-of-care testing from patients across the Johns Hopkins Health System (JHHS) were used for the study. Samples were randomly selected for whole viral genome sequencing. The sequence-based pEpitope model was used to estimate the predicted vaccine efficacy (pVE) for circulating H3N2 viruses. Clinical data were collected and associated with viral genomic data., Results: A total of 121 683 respiratory specimens were tested for influenza at JHHS between 1 September 2021 and 31 December 2022. Among them, 6071 (4.99%) tested positive for influenza A. Of these, 805 samples were randomly selected for sequencing, with hemagglutinin (HA) segments characterized for 610 samples. Among the characterized samples, 581 were H3N2 (95.2%). Phylogenetic analysis of HA segments revealed the exclusive circulation of H3N2 viruses with HA segments of the 3C.2a1b.2a.2 clade. Analysis of a total of 445 complete H3N2 genomes revealed reassortments; 200 of 227 of the 2022/2023 season genomes (88.1%) were found to have reassorted with clade 3C.2a1b.1a. The pVE was estimated to be -42.53% for the 2021/2022 season and 30.27% for the 2022/2023 season. No differences in clinical presentations or admissions were observed between the 2 seasons., Conclusions: The increased numbers of cases and genomic diversity of influenza A(H3N2) during the 2022/2023 season were not associated with a change in disease severity compared to the previous influenza season., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Understanding Influenza B virus infections is of critical importance in our efforts to control severe influenza and influenza-related diseases. Until 2020, two genetic lineages of influenza B virus-Yamagata and Victoria-circulated in the population. These lineages are antigenically distinct, but the differences in virus replication or the induction of host cell responses after infection have not been carefully studied. Recent IBV clinical isolates of both lineages were obtained from influenza surveillance efforts of the Johns Hopkins Center of Excellence in Influenza Research and Response and characterized in vitro. B/Victoria and B/Yamagata clinical isolates were recognized less efficiently by serum from influenza-vaccinated individuals in comparison to the vaccine strains. B/Victoria lineages formed smaller plaques on MDCK cells compared to B/Yamagata, but infectious virus production in primary human nasal epithelial cell (hNEC) cultures showed no differences. While ciliated epithelial cells were the dominant cell type infected by both lineages, B/Victoria lineages had a slight preference for MUC5AC-positive cells, and B/Yamagata lineages infected more basal cells. Finally, while both lineages induced a strong interferon response 48 h after infection of hNEC cultures, the B/Victoria lineages showed a much stronger induction of interferon-related signaling pathways compared to B/Yamagata. This demonstrates that the two influenza B virus lineages differ not only in their antigenic structure but also in their ability to induce host innate immune responses.

Background: Integration of a sensitive point-of-care (POC) HIV viral load (VL) test into screening algorithms may help detect acute HIV infection earlier, identify people with HIV (PWH) who are not virally suppressed, and facilitate earlier referral to antiretroviral therapy (ART), or evaluation for pre-exposure prophylaxis (PrEP). This report describes a randomized clinical trial sponsored by the Centers for Disease Control and Prevention (CDC): "Ending the HIV Epidemic Through Point-of-Care Technologies" (EHPOC). The study's primary aim is to evaluate the use of a POC HIV VL test as part of a testing approach and assess the impact on time to linkage to ART or PrEP. The study will recruit people in Baltimore, Maryland, including patients attending a hospital emergency department, patients attending an infectious disease clinic, and people recruited via community outreach. The secondary aim is to evaluate the performance characteristics of two rapid HIV antibody tests approved by the United States Food and Drug Administration (FDA)., Methods: The study will recruit people 18 years or older who have risk factors for HIV acquisition and are not on PrEP, or PWH who are not taking ART. Participants will be randomly assigned to either the control arm or the intervention arm. Participants randomized to the control arm will only receive the standard-of-care (SOC) HIV screening tests. Intervention arm participants will receive a POC HIV VL test in addition to the SOC HIV diagnostic screening tests. Follow up will consist of an interim phone survey conducted at week-4 and an in-person week-12 visit. Demographic and behavioral information, and oral fluid and blood specimens will be collected at enrollment and at week-12. Survey data will be captured in a Research Electronic Data Capture (REDCap) database. Participants in both arms will be referred for either ART or PrEP based on their HIV test results., Discussion: The EHPOC trial will explore a novel HIV diagnostic technology that can be performed at the POC and provide viral assessment. The study may help inform HIV testing algorithms and contribute to the evidence to support same day ART and PrEP recommendations., Trial Registration: NIH ClinicalTrials.gov NCT04793750. Date: 11 March 2021., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: Limited data on respiratory infections are available from sub-Saharan Africa during the COVID-19 pandemic. The objective of this study was to evaluate the burden of respiratory viruses in rural Zambia from 2019-2021., Methods: Surveillance was initiated at Macha Hospital in Zambia in December 2018. Each week, patients with respiratory symptoms were enrolled from the outpatient clinic. Nasopharyngeal samples were collected and tested for respiratory pathogens. The prevalence of respiratory symptoms and viruses in 2021 was compared to results from 2019 and 2020., Results: After seeing few cases of influenza virus and respiratory syncytial virus in 2020, a return to prepandemic levels was observed in 2021. Rhinovirus/enterovirus, parainfluenza virus 1-4, and adenovirus circulated from 2019 to 2021, while human metapneumovirus and human coronaviruses (HKU1, 229E, OC43, and NL63 subtypes) were observed sporadically. SARS-CoV-2 was observed consistently in 2021 after being first identified in December 2020. The proportion of participants with co-infections in 2021 (11.6%) was significantly higher than in 2019 (6.9%) or 2020 (7.7%)., Conclusion: Declines in influenza virus and respiratory syncytial virus were reversed once public health measures were lifted. Respiratory viruses contributed to a significant burden of respiratory infections in 2021. This study provides important information about respiratory viruses in this changing context and underrepresented region., Competing Interests: The authors have no competing interests to declare., (© 2023 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.)

Objectives: Recent research has helped define the complex pathways in sepsis, affording new opportunities for advancing diagnostics tests. Given significant advances in the field, a group of academic investigators from emergency medicine, intensive care, pathology, and pharmacology assembled to develop consensus around key gaps and potential future use for emerging rapid host response diagnostics assays in the emergency department (ED) setting., Methods: A modified Delphi study was conducted that included 26 panelists (expert consensus panel) from multiple specialties. A smaller steering committee first defined a list of Delphi statements related to the need for and future potential use of a hypothetical sepsis diagnostic test in the ED. Likert scoring was used to assess panelists agreement or disagreement with statements. Two successive rounds of surveys were conducted and consensus for statements was operationally defined as achieving agreement or disagreement of 75% or greater., Results: Significant gaps were identified related to current tools for assessing risk of sepsis in the ED. Strong consensus indicated the need for a test providing an indication of the severity of dysregulated host immune response, which would be helpful even if it did not identify the specific pathogen. Although there was a relatively high degree of uncertainty regarding which patients would most benefit from the test, the panel agreed that an ideal host response sepsis test should aim to be integrated into ED triage and thus should produce results in less than 30 minutes. The panel also agreed that such a test would be most valuable for improving sepsis outcomes and reducing rates of unnecessary antibiotic use., Conclusion: The expert consensus panel expressed strong consensus regarding gaps in sepsis diagnostics in the ED and the potential for new rapid host response tests to help fill these gaps. These finding provide a baseline framework for assessing key attributes of evolving host response diagnostic tests for sepsis in the ED., Competing Interests: This study was funded by Cytovale, Inc. Expert panelists were compensated for their time for participation. C.K.K. has received funding personally from Cytovale for consulting, H.B.N. has received funding personally from Cytovale for consulting, R.C.J. has received funding personally from Cytovale for consulting, L.S.M. has received funding personally from Cytovale for consulting, N.A.L. has stock options for Cytovale and Inflammatix, H.R.O. reports no conflict of interest, M.A.P. has received funding personally from Cytovale and Opticyte for consulting. M.A.P. reports grant money to Hennepin County Medical Center to conduct research conceived and sponsored by Endpoint Health, T.W.R.’s institution has received grant funding from the National Institutes of Health, Centers for Disease Control and Prevention, and the US Department of Defense, and Endpoint Health, Inc. for investigator‐initiated research. T.W.R. has received funding personally from Cumberland Pharmaceuticals, Inc. and Cytovale, Inc. for consulting and from Sanofi, Inc. for DSMB membership, W.H.S. has received funding personally from Cytovale for consulting, R.E.R. has received funding personally from Cytovale for consulting for serving on an expert advisory committee and providing oversight in formulating, writing and editing this study. R.E.R. previously served on paid expert advisory panels for Abbott, Roche, Cepheid, MeMed, and Inflammatix; R.E.R.’s institution received support from the National Institutes of Health and Biomedical Advanced Research and Development Authority/US Department of Health and Human Services for research in infectious disease diagnostics in emergency settings., (© 2023 The Authors. JACEP Open published by Wiley Periodicals LLC on behalf of American College of Emergency Physicians.)

There is a significant number of Emergency Department (ED) patients with known chronic hepatitis C virus (HCV) infection who have not been treated with directly acting antivirals. We implemented a pilot ED-based linkage-to-care program to address this need and evaluated the impact of the program using the HCV Care Continuum metrics. Between March 2015 and May 2016, dedicated patient care navigators identified HCV RNA-positive patients in an urban ED and offered expedited appointments with the on-site viral hepatitis clinic. Patient demographics and care continuum outcomes were abstracted from the EMR and analysed to determine significant factors influencing linkage-to-care (LTC) and treatment initiation rates. The ED linkage-to-care program achieved a 43% linkage-to-care rate (165/384), 22% treatment rate (84/384) and 16% sustained virologic response rate (63/384). Significant associations were found between linkage-to-care and increasing age (OR = 1.03), Medicare insurance (OR = 2.21) and having a primary care physician (PCP) (OR = 4.03). For patients who were linked, the odds of initiating treatment were also positively significantly associated with increasing age (OR = 1.04) and having a PCP (OR = 2.77). For patients who initiated treatment, the odds of sustained virologic response were marginally associated with having a PCP (OR = 4.92).Our ED linkage-to-care program utilized care coordination to successfully link nearly half of approached HCV RNA-positive patients to care. This design can be feasibly replicated by other EDs given limited non-clinical training required for linkage-to-care staff. Adoption of similar programs in other EDs may improve the rates of LTC and treatment initiation for previously diagnosed HCV patients., (© 2022 John Wiley & Sons Ltd.)

Background: Hepatitis C (HCV) poses a major public health problem in the USA. While early identification is a critical priority, subsequent linkage to a treatment specialist is a crucial step that bridges diagnosed patients to treatment, cure, and prevention of ongoing transmission. Emergency departments (EDs) serve as an important clinical setting for HCV screening, although optimal methods of linkage-to-care for HCV-diagnosed individuals remain unknown. In this article, we describe the rationale and design of The Determining Effective Testing in Emergency Departments and Care Coordination on Treatment Outcomes (DETECT) for Hepatitis C (Hep C) Linkage-to-Care Trial., Methods: The DETECT Hep C Linkage-to-Care Trial will be a single-center prospective comparative effectiveness randomized two-arm parallel-group superiority trial to test the effectiveness of linkage navigation and clinician referral among ED patients identified with untreated HCV with a primary hypothesis that linkage navigation plus clinician referral is superior to clinician referral alone when using treatment initiation as the primary outcome. Participants will be enrolled in the ED at Denver Health Medical Center (Denver, CO), an urban, safety-net hospital with approximately 75,000 annual adult ED visits. This trial was designed to enroll a maximum of 280 HCV RNA-positive participants with one planned interim analysis based on methods by O'Brien and Fleming. This trial will further inform the evaluation of cost effectiveness, disparities, and social determinants of health in linkage-to-care, treatment, and disease progression., Discussion: When complete, the DETECT Hep C Linkage-to-Care Trial will significantly inform how best to perform linkage-to-care among ED patients identified with HCV., Trial Registration: ClinicalTrials.gov ID: NCT04026867 Original date: July 1, 2019 URL: https://clinicaltrials.gov/ct2/show/NCT04026867., (© 2023. The Author(s).)

Vaccines are effective tools to prevent COVID-19-related morbidity. However, coverage is low throughout sub-Saharan Africa. Uptake of public health measures, perceptions of COVID-19 illness and vaccines, and intention to vaccinate were evaluated in 2021-2022 in rural Zambia. Adherence to public health measures, perceptions of COVID-19 risk and severity, and vaccine acceptance increased significantly over time, particularly in December 2021, coinciding with the fourth pandemic wave and relaunch of the national vaccine campaign. Vaccine acceptance was associated with perceptions of vaccine safety and effectiveness, but not disease severity. These findings highlight the importance of strong pandemic response and public communication for increased uptake of mitigatory measures, including vaccine acceptance.

The first pandemic of the 21st century was caused by an H1N1 influenza A virus (IAV) introduced from pigs into humans, highlighting the importance of swine as reservoirs for pandemic viruses. Two major lineages of swine H1 circulate in North America: the 1A classical swine lineage (including that of the 2009 H1N1 pandemic) and the 1B human seasonal-like lineage. Here, we investigated the evolution of these H1 IAV lineages in North American swine and their potential pandemic risk. We assessed the antigenic distance between the HA of representative swine H1 and human seasonal vaccine strains (1978 to 2015) in hemagglutination inhibition (HI) assays using a panel of monovalent antisera raised in pigs. Antigenic cross-reactivity varied by strain but was associated with genetic distance. Generally, the swine 1A lineage viruses that seeded the 2009 H1 pandemic were antigenically most similar to the H1 pandemic vaccine strains, with the exception of viruses in the genetic clade 1A.1.1.3, which had a two-amino acid deletion mutation near the receptor-binding site, which dramatically reduced antibody recognition. The swine 1B lineage strains, which arose from previously circulating (pre-2009 pandemic) human seasonal viruses, were more antigenically similar to pre-2009 human seasonal H1 vaccine viruses than post-2009 strains. Human population immunity was measured by cross-reactivity in HI assays to representative swine H1 strains. There was a broad range of titers against each swine strain that was not associated with age, sex, or location. However, there was almost no cross-reactivity in human sera to the 1A.1.1.3 and 1B.2.1 genetic clades of swine viruses, and the 1A.1.1.3 and 1B.2.1 clades were also the most antigenically distant to the human vaccine strains. Our data demonstrate that the antigenic distances of representative swine strains from human vaccine strains represent an important part of the rational assessment of swine IAV for zoonotic risk research and pandemic preparedness prioritization. IMPORTANCE Human H1 influenza A viruses (IAV) spread to pigs in North America, resulting in a sustained circulation of two major groups of H1 viruses in swine. We quantified the genetic diversity of H1 in swine and measured antigenic phenotypes. We demonstrated that the swine H1 lineages were significantly different from the human vaccine strains and that this antigenic dissimilarity increased over time as the viruses evolved in swine. Pandemic preparedness vaccine strains for human vaccines also demonstrated a loss in similarity with contemporary swine strains. Human sera revealed a range of responses to swine IAV, including two groups of viruses with little to no immunity. The surveillance and risk assessment of IAV diversity in pig populations are essential to detect strains with reduced immunity in humans and provide critical information for pandemic preparedness.

Background: Given the steady increase of emergency department (ED) visits related to opioid overdoses, this study aims to determine the design and usability of an ED-centered mHealth patient-to-peer referral prototype tool that allows patients to refer peers to comprehensive HIV/HCV and opioid misuse prevention services., Methods: Two iterative focus group discussion (FDG) sessions and one use-case session were conducted. Eligible participants who were ≥18 years, had a history of injection drug use (IDU), and had utilized the ED in the past year were recruited through the distribution of flyers at the study institution, including the study ED. Human-centered design process was completed by using participant feedback on perceived utility, usability/accessibility, tool design, and clarity/readability to fine-tune prototype version and drive subsequent discussion sessions., Results: Sixteen consented individuals participated in at least one of the sessions. Feedback revealed that participants favored the inclusion of the webpage link on the referral card as means to bypass QR code if needed, more descriptions highlighting the exact services offered, and the fact that no personal information was required to complete the referral process. The prototype underwent several adjustments between user-centered FDG sessions, which ultimately ended in including features such as an online webpage with educational videos, SMS text-message communication system, and QR code usage into the final patient-to-peer referral tool prototype., Conclusion: The findings of this study suggest a human-centered designed patient-to-peer referral tool could be a feasible approach to linking community members at risk of IDU to HIV/HCV and opioid use-related preventive services from ED patients., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Monocyte distribution width (MDW) is a novel marker of monocyte activation, which is known to occur in the immune response to viral pathogens. Our objective was to determine the performance of MDW and other leukocyte parameters as screening tests for SARS-CoV-2 and influenza infection. This was a prospective cohort analysis of adult patients who underwent complete blood count (CBC) and SARS-CoV-2 or influenza testing in an Emergency Department (ED) between January 2020 and July 2021. The primary outcome was SARS-CoV-2 or influenza infection. Secondary outcomes were measures of severity of illness including inpatient hospitalization, critical care admission, hospital lengths of stay and mortality. Descriptive statistics and test performance measures were evaluated for monocyte percentage, MDW, white blood cell (WBC) count, and neutrophil to lymphocyte ratio (NLR). 3,425 ED patient visits were included. SARS-CoV-2 testing was performed during 1,922 visits with a positivity rate of 5.4%; influenza testing was performed during 2,090 with a positivity rate of 2.3%. MDW was elevated in patients with SARS-Cov-2 (median 23.0U; IQR 20.5-25.1) or influenza (median 24.1U; IQR 22.0-26.9) infection, as compared to those without (18.9U; IQR 17.4-20.7 and 19.1U; 17.4-21, respectively, P < 0.001). Monocyte percentage, WBC and NLR values were within normal range in patients testing positive for either virus. MDW identified SARS-CoV-2 and influenza positive patients with an area under the curve (AUC) of 0.83 (95% CI 0.79-0.86) and 0.83 (95% CI 0.77-0.88), respectively. At the accepted cut-off value of 20U for MDW, sensitivities were 83.7% (95% CI 76.5-90.8%) for SARS-CoV-2 and 89.6% (95% CI 80.9-98.2%) for influenza, compared to sensitivities below 45% for monocyte percentage, WBC and NLR. MDW negative predictive values were 98.6% (95% CI 98.0-99.3%) and 99.6% (95% CI 99.3-100.0%) respectively for SARS-CoV-2 and influenza. Monocyte Distribution Width (MDW), available as part of a routine complete blood count (CBC) with differential, may be a useful indicator of SARS-CoV-2 or influenza infection., (© 2022. The Author(s).)

Severe COVID-19 is characterized by a prothrombotic state associated with thrombocytopenia, with microvascular thrombosis being almost invariably present in the lung and other organs at postmortem examination. We evaluated the presence of antibodies to platelet factor 4 (PF4)-polyanion complexes using a clinically validated immunoassay in 100 hospitalized patients with COVID-19 with moderate or severe disease (World Health Organization score, 4 to 10), 25 patients with acute COVID-19 visiting the emergency department, and 65 convalescent individuals. Anti-PF4 antibodies were detected in 95 of 100 hospitalized patients with COVID-19 (95.0%) irrespective of prior heparin treatment, with a mean optical density value of 0.871 ± 0.405 SD (range, 0.177 to 2.706). In contrast, patients hospitalized for severe acute respiratory disease unrelated to COVID-19 had markedly lower levels of the antibodies. In a high proportion of patients with COVID-19, levels of all three immunoglobulin (Ig) isotypes tested (IgG, IgM, and IgA) were simultaneously elevated. Antibody levels were higher in male than in female patients and higher in African Americans and Hispanics than in White patients. Anti-PF4 antibody levels were correlated with the maximum disease severity score and with significant reductions in circulating platelet counts during hospitalization. In individuals convalescent from COVID-19, the antibody levels returned to near-normal values. Sera from patients with COVID-19 induced higher levels of platelet activation than did sera from healthy blood donors, but the results were not correlated with the levels of anti-PF4 antibodies. These results demonstrate that the vast majority of patients with severe COVID-19 develop anti-PF4 antibodies, which may play a role in the clinical complications of COVID-19.

Objective: A recent academic-government partnership demonstrated the feasibility of utilizing Emergency Departments (ED) as a primary site for subject enrollment in clinical trials and achieved high rates of recruitment in two U.S. EDs. Given the ongoing need to test new therapeutics for influenza and other emerging infections, we sought to describe the historical rates of participant recruitment into influenza Phase III therapeutic RCTs in various clinical venues, including EDs., Study Design: A cross-sectional study was performed of influenza therapeutic Phase III RCTs published in PubMed, Embase, Scopus, and Clinicaltrials.gov from January 2000 to June 2019., Main Outcome: To estimate the weighted-average number of influenza-positive participants enrolled per site per season in influenza therapeutic RCT conducted in clinical settings, and to describe basic trial site characteristics., Results: 47 (0.7%) of 7008 articles were included for review of which 43 of 47 (91%) included information regarding enrollment sites; of these, 2 (5%) recruited exclusively from EDs with the remainder recruiting from mixed clinical settings (inpatient, outpatient, and ED). The median enrollment per study was 326 (IQR: 110, 502.5) with a median of 11 sites per study (IQR: 2, 59.5). Included studies reported a median of 201 (IQR: 74, 344.5) confirmed influenza-positive participants per study. The pooled number of participants enrolled per site per season was 11 (95% CI: 10, 12). The pooled enrollment numbers per clinical site after excluding the two 'ED only recruitment' studies were less [10.7 (95% CI: 9.9, 11.6)] than the pooled enrollment numbers per clinical site for the two 'ED only recruitment' studies [89.5 (95% CI 89.2-89.27)]., Conclusion and Relevance: Published RCTs evaluating influenza therapeutics in clinical settings recruit participants from multiple sites but enroll relatively few participants, per site, per season. The few ED-based studies reported recruited more subjects per site per season. Untapped opportunities likely exist for EDs to participate and/or lead therapeutic RCTs for influenza or other emerging respiratory pathogens., Competing Interests: Declaration of Competing Interest The authors have declared that no competing interests exist., (Copyright © 2022 Elsevier Inc. All rights reserved.)

There has been a substantial rise in the number of publications and training opportunities on the care and treatment of emergency department (ED) patients with opioid use disorder over the past several years. The American College of Emergency Physicians recently published recommendations for providing buprenorphine to patients with opioid use disorder, but barriers to implementing this clinical practice remain. We describe the models for implementing ED-initiated buprenorphine at 4 diverse urban, academic medical centers across the country as part of a federally funded effort termed "Project ED Health." These 4 sites successfully implemented unique ED-initiated buprenorphine programs as part of a comparison of implementation facilitation to traditional educational dissemination on the uptake of ED-initiated buprenorphine. Each site describes the elements central to the ED process, including screening, treatment initiation, referral, and follow-up, while harnessing organizational characteristics, including ED culture. Finally, we discuss common facilitators to program success, including information technology and electronic medical record integration, hospital-level support, strong connections with outpatient partners, and quality improvement processes., (Copyright © 2022 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)