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An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Severe respiratory infections can result in acute respiratory distress syndrome (ARDS)1. There are no effective pharmacological therapies that have been shown to improve outcomes for patients with ARDS. Although the host inflammatory response limits spread of and eventually clears the pathogen, immunopathology is a major contributor to tissue damage and ARDS1,2. Here we demonstrate that respiratory viral infection induces distinct fibroblast activation states, which we term extracellular matrix (ECM)-synthesizing, damage-responsive and interferon-responsive states. We provide evidence that excess activity of damage-responsive lung fibroblasts drives lethal immunopathology during severe influenza virus infection. By producing ECM-remodelling enzymes-in particular the ECM protease ADAMTS4-and inflammatory cytokines, damage-responsive fibroblasts modify the lung microenvironment to promote robust immune cell infiltration at the expense of lung function. In three cohorts of human participants, the levels of ADAMTS4 in the lower respiratory tract were associated with the severity of infection with seasonal or avian influenza virus. A therapeutic agent that targets the ECM protease activity of damage-responsive lung fibroblasts could provide a promising approach to preserving lung function and improving clinical outcomes following severe respiratory infections.
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Proteína ADAMTS4/metabolismo , Fibroblastos/enzimología , Fibroblastos/patología , Virus de la Influenza A/patogenicidad , Pulmón/patología , Pulmón/fisiopatología , Proteína ADAMTS4/antagonistas & inhibidores , Animales , Aves/virología , Matriz Extracelular/enzimología , Perfilación de la Expresión Génica , Humanos , Gripe Aviar/virología , Gripe Humana/patología , Gripe Humana/terapia , Gripe Humana/virología , Interferones/inmunología , Interferones/metabolismo , Antígenos Comunes de Leucocito/metabolismo , Pulmón/enzimología , Pulmón/virología , Ratones , Síndrome de Dificultad Respiratoria/enzimología , Síndrome de Dificultad Respiratoria/fisiopatología , Síndrome de Dificultad Respiratoria/terapia , Síndrome de Dificultad Respiratoria/virología , Estaciones del Año , Análisis de la Célula Individual , Células del Estroma/metabolismoRESUMEN
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.
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COVID-19 , Trombocitopenia , Humanos , Masculino , Femenino , Factor Plaquetario 4 , Heparina , Anticuerpos , Factores Inmunológicos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Despite many studies evaluating lung ultrasound (LUS) for COVID-19 prognostication, the generalizability and utility across clinical settings is uncertain. METHODS: Adults (≥18 years of age) with COVID-19 were enrolled at two 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 were enrolled (57.9% female, median age 45.0 years, interquartile range [IQR]: 31.5, 58.0). Nine participants clinically deteriorated. The top predictors of worsening disease in the validation cohort measured by cross-validated area under the curve (cvAUC) were B-lines (0.88, 95% confidence interval [CI]: 0.87, 0.90), discrete B-lines (0.87, 95% CI: 0.85, 0.88), oxygen saturation (0.82, 95%: CI:0.81, 0.84), and A-lines (0.80, 95% CI: 0.78, 0.81). CONCLUSIONS: In an international multisite POCUS cohort, LUS parameters had high discriminative accuracy. Ultrasound can be applied towards triage across a wide breadth of care settings during a pandemic.
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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.
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Renina , Sepsis , Humanos , Ácido Ascórbico/uso terapéutico , Tiamina/uso terapéutico , Enzima Convertidora de Angiotensina 2 , Enfermedad Crítica , Sistema Renina-Angiotensina/fisiología , Vitaminas/uso terapéutico , Biomarcadores , Esteroides/uso terapéutico , Sepsis/tratamiento farmacológicoRESUMEN
BACKGROUND: COVID-19 stay-at-home orders and research restrictions halted recruitment and follow-up of clinical research patients. While clinical research has resumed, it is an open question whether research participation has returned to levels similar to those before COVID-19. METHODS: We utilized data from the TECH-PN (NCT# NCT03828994) study, a single-center RCT enrolling 13-25-year-olds with mild-moderate pelvic inflammatory disease (PID) receiving ambulatory care. We examined enrollment patterns before COVID-19 and during/after COVID-19 among those assessed for eligibility by estimating the average rate of recruitment visits for each period. We focused on this monthly rate by pandemic status, the length of stay (LOS) by pandemic status, as well as the relationship between the LOS and patient demographics. Descriptive analyses were conducted, including Student's t-test to compare rates between time periods and a Chi-square test to compare the proportion refusing enrollment. RESULTS: The monthly enrollment rate during/post-pandemic was significantly lower than before COVID-19 (4.8 per month compared to 7.4 per month, p < 0.001). However, eligible participants' age, race, and insurance type were similar pre- and during/post-pandemic. Among eligible patients, LOS for receiving PID care was slightly increased, from a median of 5.4 hours to 6.4 hours (p = 0.650), and the rate of refusal to participate among those eligible was similar (23% versus 27%, p = 0.362). There was a similar number of ineligible patients due to inpatient admissions during both periods. CONCLUSION: COVID-19 pandemic restrictions negatively impacted recruitment into this RCT. Enrollment differences may reflect ongoing perceptions of restrictions in care access or a hesitancy to use health services. More research is needed to stabilize access to ambulatory STI/PID care and access to clinical trials.
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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 DPP® 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: 327 patients were consented and enrolled. The diagnostic sensitivity and specificity of the Chembio POC assay for HIV was 96.5% (95% CI: 90.1%, 99.3%) and 99.6% (95% CI: 97.7%, 100.0%), respectively, and for syphilis was 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 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 they would recommend using the test in EDs. CONCLUSIONS: The Chembio DPP® 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.
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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.
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Análisis Costo-Beneficio , Servicio de Urgencia en Hospital , Infecciones por VIH , Tamizaje Masivo , Humanos , Servicio de Urgencia en Hospital/economía , Infecciones por VIH/diagnóstico , Infecciones por VIH/economía , Tamizaje Masivo/economía , Tamizaje Masivo/métodos , Femenino , Adulto , Masculino , Estados Unidos , Persona de Mediana Edad , Prueba de VIH/economía , Prueba de VIH/métodos , Adulto JovenRESUMEN
Human-to-swine transmission of influenza A virus (IAV) repeatedly occurs, leading to sustained transmission and increased diversity in swine; human seasonal H3N2 introductions occurred in the 1990s and 2010s and were maintained in North American swine. Swine H3N2 strains were subsequently associated with zoonotic infections, highlighting the need to understand the risk of endemic swine IAV to humans. We quantified antigenic distances between swine H3N2 and human seasonal vaccine strains from 1973 to 2014 using a panel of monovalent antisera raised in pigs in hemagglutination inhibition (HI) assays. Swine H3N2 lineages retained the closest antigenic similarity to human vaccine strains from the decade of incursion. Swine lineages from the 1990s were antigenically more similar to human vaccine strains of the mid-1990s but had substantial distance from recent human vaccine strains. In contrast, lineages from the 2010s were closer to human vaccine strains from 2011 and 2014 and the most antigenically distant from human vaccine strains prior to 2007. HI assays using ferret antisera demonstrated that swine lineages from the 1990s and 2010s had significant fold reductions compared to the homologous HI titer of the nearest pandemic preparedness candidate vaccine virus (CVV) or seasonal vaccine strain. The assessment of postinfection and postvaccination human serum cohorts demonstrated limited cross-reactivity to swine H3N2 from the 1990s, especially in older adults born before the 1970s. We identified swine strains to which humans are likely to lack population immunity or are not protected against by a current human seasonal vaccine or CVV to use in prioritizing future human CVV strain selection. IMPORTANCE Human H3N2 influenza A viruses spread to pigs in North America in the 1990s and more recently in the 2010s. These cross-species events led to sustained circulation and increased H3N2 diversity in pig populations. The evolution of H3N2 in swine led to a reduced similarity to human seasonal H3N2 and the vaccine strains used to protect human populations. We quantified the antigenic phenotypes and found that North American swine H3N2 lineages retained more antigenic similarity to historical human vaccine strains from the decade of incursion but had substantial differences compared to recent human vaccine strains. Additionally, pandemic preparedness vaccine strains demonstrated a loss of similarity to contemporary swine strains. Finally, human sera revealed that although these adults had antibodies against human H3N2 strains, many had limited immunity to swine H3N2, especially older adults born before 1970. Antigenic assessment of swine H3N2 provides critical information for pandemic preparedness and candidate vaccine development.
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Subtipo H3N2 del Virus de la Influenza A/genética , Infecciones por Orthomyxoviridae/virología , Zoonosis Virales/virología , Animales , Deriva y Cambio Antigénico , Variación Antigénica , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Humanos , Sueros Inmunes/inmunología , Subtipo H3N2 del Virus de la Influenza A/clasificación , Subtipo H3N2 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/genética , Gripe Humana/transmisión , Gripe Humana/virología , Infecciones por Orthomyxoviridae/transmisión , Filogenia , Medición de Riesgo , Porcinos , Zoonosis Virales/transmisiónRESUMEN
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.
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Hepatitis C Crónica , Hepatitis C , Anciano , Humanos , Estados Unidos , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Tamizaje Masivo , Medicare , Hepatitis C/diagnóstico , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Hepacivirus/genética , Servicio de Urgencia en Hospital , ARNRESUMEN
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.
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Infecciones por VIH , Sistemas de Atención de Punto , Estados Unidos , Humanos , Baltimore , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Carga Viral , Prueba de VIHRESUMEN
BACKGROUND: Several inflammatory cytokines are upregulated in severe coronavirus disease 2019 (COVID-19). We compared cytokines in COVID-19 versus influenza to define differentiating features of the inflammatory response to these pathogens and their association with severe disease. Because elevated body mass index (BMI) is a known risk factor for severe COVID-19, we examined the relationship of BMI to cytokines associated with severe disease. METHODS: Thirty-seven cytokines and chemokines were measured in plasma from 135 patients with COVID-19, 57 patients with influenza, and 30 healthy controls. Controlling for BMI, age, and sex, differences in cytokines between groups were determined by linear regression and random forest prediction was used to determine the cytokines most important in distinguishing severe COVID-19 and influenza. Mediation analysis was used to identify cytokines that mediate the effect of BMI and age on disease severity. RESULTS: Interleukin-18 (IL-18), IL-1ß, IL-6, and tumor necrosis factor-α (TNF-α) were significantly increased in COVID-19 versus influenza patients, whereas granulocyte macrophage colony-stimulating factor, interferon-γ (IFN-γ), IFN-λ1, IL-10, IL-15, and monocyte chemoattractant protein 2 were significantly elevated in the influenza group. In subgroup analysis based on disease severity, IL-18, IL-6, and TNF-α were elevated in severe COVID-19, but not in severe influenza. Random forest analysis identified high IL-6 and low IFN-λ1 levels as the most distinct between severe COVID-19 and severe influenza. Finally, IL-1RA was identified as a potential mediator of the effects of BMI on COVID-19 severity. CONCLUSIONS: These findings point to activation of fundamentally different innate immune pathways in severe acute respiratory syndrome coronavirus 2 and influenza infection, and emphasize drivers of severe COVID-19 to focus both mechanistic and therapeutic investigations.
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COVID-19 , Gripe Humana , Quimiocinas , Citocinas , Humanos , SARS-CoV-2RESUMEN
BACKGROUND: Whereas safe, curative treatments for hepatitis C virus (HCV) have been available since 2015, there are still 58 million infected persons worldwide, and global elimination may require new paradigms. We sought to understand the acceptability of approaches to long-acting HCV treatment. METHODS: A cross-sectional, 43-question survey was administered to 1457 individuals with or at risk of HCV at 28 sites in 9 countries to assess comparative interest in a variety of long-acting strategies in comparison with oral pills. RESULTS: Among HCV-positive participants, 37.7% most preferred an injection, 5.6% an implant, and 6% a gastric residence device, as compared with 50.8% who stated they would most prefer taking 1-3 pills per day. When compared directly to taking pills, differences were observed in the relative preference for an injection based on age (P<.001), location (P<.001), and prior receipt of HCV treatment (P=.005) but not sex. When an implant was compared with pills, greater preference was represented by women (P=.01) and adults of younger ages (P=.01 per 5 years). Among participants without HCV, 49.5% believed that injections are stronger than pills and 34.7% preferred taking injections to pills. Among those at-risk participants who had received injectable medications in the past, 123 of 137 (89.8%) expressed willingness to receive one in the future. CONCLUSIONS: These data point to high acceptability of long-acting treatments, which for a substantial minority might even be preferred to pills for the treatment of HCV infection. Long-acting treatments for HCV infection might contribute to global efforts to eliminate hepatitis C.
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Hepacivirus , Hepatitis C , Adulto , Antivirales/uso terapéutico , Preescolar , Estudios Transversales , Femenino , Hepatitis C/tratamiento farmacológico , HumanosRESUMEN
Emergency departments (EDs) can serve as surveillance sites for infectious diseases. The objective of this study was to determine the burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to monitor the prevalence of vaccination against coronavirus disease 2019 (COVID-19) among patients attending an urban ED in Baltimore City. Using 1,914 samples of known exposure status, we developed an algorithm to differentiate previously infected, vaccinated, and unexposed individuals using a combination of antibody assays. We applied this testing algorithm to 4,360 samples from ED patients obtained in the spring of 2020 and 2021. Using multinomial logistic regression, we determined factors associated with infection and vaccination. For the algorithm, sensitivity and specificity for identifying vaccinated individuals were 100% and 99%, respectively, and 84% and 100% for previously infected individuals. Among the ED subjects, seroprevalence to SARS-CoV-2 increased from 2% to 24% between April 2020 and March 2021. Vaccination prevalence rose to 11% by mid-March 2021. Marked differences in burden of disease and vaccination coverage were seen by sex, race, and ethnicity. Hispanic patients, though accounting for 7% of the study population, had the highest relative burden of disease (17% of total infections) but with similar vaccination rates. Women and white individuals were more likely to be vaccinated than men or Black individuals. Individuals previously infected with SARS-CoV-2 can often be differentiated from vaccinated individuals using a serologic testing algorithm. The utility of this algorithm can aid in monitoring SARS-CoV-2 exposure and vaccination uptake frequencies and can potentially reflect gender, race, and ethnic health disparities.
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COVID-19 , SARS-CoV-2 , COVID-19/epidemiología , COVID-19/prevención & control , Servicio de Urgencia en Hospital , Femenino , Humanos , Masculino , Estudios Seroepidemiológicos , Población BlancaRESUMEN
The continual emergence of novel influenza A strains from non-human hosts requires constant vigilance and the need for ongoing research to identify strains that may pose a human public health risk. Since 1999, canine H3 influenza A viruses (CIVs) have caused many thousands or millions of respiratory infections in dogs in the United States. While no human infections with CIVs have been reported to date, these viruses could pose a zoonotic risk. In these studies, the National Institutes of Allergy and Infectious Diseases (NIAID) Centers of Excellence for Influenza Research and Surveillance (CEIRS) network collaboratively demonstrated that CIVs replicated in some primary human cells and transmitted effectively in mammalian models. While people born after 1970 had little or no pre-existing humoral immunity against CIVs, the viruses were sensitive to existing antivirals and we identified a panel of H3 cross-reactive human monoclonal antibodies (hmAbs) that could have prophylactic and/or therapeutic value. Our data predict these CIVs posed a low risk to humans. Importantly, we showed that the CEIRS network could work together to provide basic research information important for characterizing emerging influenza viruses, although there were valuable lessons learned.
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Enfermedades Transmisibles Emergentes/veterinaria , Enfermedades de los Perros/virología , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Subtipo H3N8 del Virus de la Influenza A/aislamiento & purificación , Virus de la Influenza A/aislamiento & purificación , Zoonosis/virología , Animales , Enfermedades Transmisibles Emergentes/transmisión , Enfermedades Transmisibles Emergentes/virología , Enfermedades de los Perros/transmisión , Perros , Hurones , Cobayas , Humanos , Subtipo H3N2 del Virus de la Influenza A/clasificación , Subtipo H3N2 del Virus de la Influenza A/genética , Subtipo H3N8 del Virus de la Influenza A/clasificación , Subtipo H3N8 del Virus de la Influenza A/genética , Virus de la Influenza A/clasificación , Virus de la Influenza A/genética , Gripe Humana/transmisión , Gripe Humana/virología , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Estados Unidos , Zoonosis/transmisiónRESUMEN
OBJECTIVES: With the emergence of the COVID-19 pandemic, restrictions were implemented globally to control the virus. Data on respiratory pathogens in sub-Saharan Africa during the COVID-19 pandemic are scarce. This analysis was conducted to evaluate patterns of respiratory pathogens in rural Zambia before and during the first year of the pandemic. METHODS: Surveillance was established in December 2018 at Macha Hospital in southern Zambia. Patients with respiratory symptoms in the outpatient and inpatient clinics were recruited. Nasopharyngeal samples were collected and tested for respiratory pathogens. The prevalence of respiratory symptoms and pathogens was evaluated and compared in the first (December 10, 2018-December 9, 2019) and second (December 10, 2019-November 30, 2020) years of surveillance. RESULTS: Outpatient visits and admissions for respiratory illness significantly decreased from the first to second year, especially among children. SARS-CoV-2 was not detected from any participants in Year 2. Among outpatients and inpatients with respiratory symptoms, the prevalence of respiratory syncytial virus and influenza viruses decreased from the first to second year. In contrast, the prevalence of rhinovirus/enterovirus, metapneumovirus and parainfluenza virus increased. CONCLUSIONS: The epidemiology of respiratory viruses in rural Zambia changed during the first year of the COVID-19 pandemic, suggesting that public health interventions may have had an impact on the introduction and circulation of respiratory pathogens in this area.
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COVID-19 , Virus Sincitial Respiratorio Humano , Infecciones del Sistema Respiratorio , Virus , COVID-19/epidemiología , Niño , Humanos , Pandemias , Infecciones del Sistema Respiratorio/epidemiología , Zambia/epidemiologíaRESUMEN
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.
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Buprenorfina , Trastornos Relacionados con Opioides , Humanos , Buprenorfina/uso terapéutico , Tratamiento de Sustitución de Opiáceos , Antagonistas de Narcóticos/uso terapéutico , Alta del Paciente , Servicio de Urgencia en Hospital , Trastornos Relacionados con Opioides/tratamiento farmacológico , Derivación y ConsultaRESUMEN
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.
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Gripe Humana , Humanos , Gripe Humana/tratamiento farmacológico , Estudios Transversales , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
New approaches to pelvic inflammatory disease (PID) care among adolescents and young adults (AYAs) that optimize self-care and personalize treatment are warranted to address age and racial-ethnic PID-related health disparities. Here we describe the 13-month preliminary feasibility and acceptability outcomes of recruitment, retention, and intervention delivery for Technology Enhanced Community Health Precision Nursing (TECH-PN) randomized controlled trial. Urban AYAs 13-25 years assigned female sex at birth with acute mild-moderate PID provided baseline and follow-up interview data and vaginal specimens for sexually transmitted infection (STI), cytokine, and microbiota assessment. All participants received medications and text-messaging support. Participants were block randomized to either control or intervention. Control participants received 1 community nursing visit with self-management for interim care per national guidelines. Intervention participants received unlimited precision care services driven by interim STI and macrolide resistance testing results by an advanced practice provider. In the first 13 months, 75.2% patients were eligible, and 76.1% of eligible patients enrolled. Of the participants, 94% completed the intervention and 96%, 91%, and 89%, respectively, completed their 14-, 30-, and 90-day visits. Baseline laboratory results revealed infection rates that were highest for Mycoplasma genitalium (45%) followed by Chlamydia trachomatis (31%). Preliminary enrollment, STI, intervention delivery, and retention data demonstrate the feasibility and acceptability of the TECH-PN intervention and support rationale for precision care for PID among urban AYAs. ClinicalTrials.gov Identifier. NCT03828994.
Asunto(s)
Atención Ambulatoria/normas , Antibacterianos/uso terapéutico , Enfermería en Salud Comunitaria/normas , Accesibilidad a los Servicios de Salud , Disparidades en Atención de Salud , Enfermedad Inflamatoria Pélvica/diagnóstico , Adolescente , Adulto , Femenino , Humanos , Atención Dirigida al Paciente , Enfermedad Inflamatoria Pélvica/tratamiento farmacológico , Enfermedad Inflamatoria Pélvica/epidemiología , Adulto JovenRESUMEN
We assessed the performance of the CoronaCHEK lateral flow assay on samples from Uganda and Baltimore to determine the impact of geographic origin on assay performance. Plasma samples from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR-positive individuals (Uganda, 78 samples from 78 individuals, and Baltimore, 266 samples from 38 individuals) and from prepandemic individuals (Uganda, 1,077, and Baltimore, 532) were evaluated. Prevalence ratios (PR) were calculated to identify factors associated with a false-positive test. After the first positive PCR in Ugandan samples, the sensitivity was 45% (95% confidence interval [CI], 24,68) at 0 to 7 days, 79% (95% CI, 64 to 91) at 8 to 14 days, and 76% (95% CI, 50 to 93) at >15 days. In samples from Baltimore, sensitivity was 39% (95% CI, 30 to 49) at 0 to 7 days, 86% (95% CI, 79 to 92) at 8 to 14 days, and 100% (95% CI, 89 to 100) at 15 days after positive PCR. The specificity of 96.5% (95% CI, 97.5 to 95.2) in Ugandan samples was significantly lower than that in samples from Baltimore, 99.3% (95% CI, 98.1 to 99.8; P < 0.01). In Ugandan samples, individuals with a false-positive result were more likely to be male (PR, 2.04; 95% CI, 1.03,3.69) or individuals who had had a fever more than a month prior to sample acquisition (PR, 2.87; 95% CI, 1.12 to 7.35). Sensitivity of the CoronaCHEK was similar in samples from Uganda and Baltimore. The specificity was significantly lower in Ugandan samples than in Baltimore samples. False-positive results in Ugandan samples appear to correlate with a recent history of a febrile illness, potentially indicative of a cross-reactive immune response in individuals from East Africa.