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Crimean-Congo hemorrhagic fever virus (CCHFV) is the most geographically widespread tickborne viral infection worldwide and has a fatality rate of up to 62%. Despite its widespread range and high fatality rate, no vaccines or treatments are currently approved by regulatory agencies in the United States or Europe. Supportive treatment remains the standard of care, but the use of antiviral medications developed for other viral infections have been considered. We reviewed published literature to summarize the main aspects of CCHFV infection in humans. We provide an overview of diagnostic testing and management and medical countermeasures, including investigational vaccines and limited therapeutics. CCHFV continues to pose a public health threat because of its wide geographic distribution, potential to spread to new regions, propensity for genetic variability, potential for severe and fatal illness, and limited medical countermeasures for prophylaxis and treatment. Clinicians should become familiar with available diagnostic and management tools for CCHFV infections in humans.
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Antivirales , Virus de la Fiebre Hemorrágica de Crimea-Congo , Fiebre Hemorrágica de Crimea , Fiebre Hemorrágica de Crimea/diagnóstico , Fiebre Hemorrágica de Crimea/terapia , Fiebre Hemorrágica de Crimea/tratamiento farmacológico , Humanos , Virus de la Fiebre Hemorrágica de Crimea-Congo/genética , Antivirales/uso terapéutico , Animales , Manejo de la Enfermedad , Vacunas ViralesRESUMEN
Crimean-Congo hemorrhagic fever (CCHF) is a tickborne infection that can range from asymptomatic to fatal and has been described in >30 countries. Early identification and isolation of patients with suspected or confirmed CCHF and the use of appropriate prevention and control measures are essential for preventing human-to-human transmission. Here, we provide an overview of the epidemiology, clinical features, and prevention and control of CCHF. CCHF poses a continued public health threat given its wide geographic distribution, potential to spread to new regions, propensity for genetic variability, and potential for severe and fatal illness, in addition to the limited medical countermeasures for prophylaxis and treatment. A high index of suspicion, comprehensive travel and epidemiologic history, and clinical evaluation are essential for prompt diagnosis. Infection control measures can be effective in reducing the risk for transmission but require correct and consistent application.
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Virus de la Fiebre Hemorrágica de Crimea-Congo , Fiebre Hemorrágica de Crimea , Fiebre Hemorrágica de Crimea/epidemiología , Fiebre Hemorrágica de Crimea/prevención & control , Fiebre Hemorrágica de Crimea/transmisión , Fiebre Hemorrágica de Crimea/diagnóstico , Fiebre Hemorrágica de Crimea/virología , Humanos , Virus de la Fiebre Hemorrágica de Crimea-Congo/genética , Animales , Garrapatas/virologíaRESUMEN
Crimean-Congo hemorrhagic fever (CCHF), caused by CCHF virus, is a tickborne disease that can cause a range of illness outcomes, from asymptomatic infection to fatal viral hemorrhagic fever; the disease has been described in >30 countries. We conducted a literature review to provide an overview of the virology, pathogenesis, and pathology of CCHF for clinicians. The virus life cycle and molecular interactions are complex and not fully described. Although pathogenesis and immunobiology are not yet fully understood, it is clear that multiple processes contribute to viral entry, replication, and pathological damage. Limited autopsy reports describe multiorgan involvement with extravasation and hemorrhages. Advanced understanding of CCHF virus pathogenesis and immunology will improve patient care and accelerate the development of medical countermeasures for CCHF.
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Virus de la Fiebre Hemorrágica de Crimea-Congo , Fiebre Hemorrágica de Crimea , Virus de la Fiebre Hemorrágica de Crimea-Congo/patogenicidad , Virus de la Fiebre Hemorrágica de Crimea-Congo/fisiología , Fiebre Hemorrágica de Crimea/virología , Fiebre Hemorrágica de Crimea/patología , Humanos , Animales , Garrapatas/virología , Replicación ViralRESUMEN
BACKGROUND: Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known. METHODS: We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19. All the patients received remdesivir (≤10 days) and either baricitinib (≤14 days) or placebo (control). The primary outcome was the time to recovery. The key secondary outcome was clinical status at day 15. RESULTS: A total of 1033 patients underwent randomization (with 515 assigned to combination treatment and 518 to control). Patients receiving baricitinib had a median time to recovery of 7 days (95% confidence interval [CI], 6 to 8), as compared with 8 days (95% CI, 7 to 9) with control (rate ratio for recovery, 1.16; 95% CI, 1.01 to 1.32; P = 0.03), and a 30% higher odds of improvement in clinical status at day 15 (odds ratio, 1.3; 95% CI, 1.0 to 1.6). Patients receiving high-flow oxygen or noninvasive ventilation at enrollment had a time to recovery of 10 days with combination treatment and 18 days with control (rate ratio for recovery, 1.51; 95% CI, 1.10 to 2.08). The 28-day mortality was 5.1% in the combination group and 7.8% in the control group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09). Serious adverse events were less frequent in the combination group than in the control group (16.0% vs. 21.0%; difference, -5.0 percentage points; 95% CI, -9.8 to -0.3; P = 0.03), as were new infections (5.9% vs. 11.2%; difference, -5.3 percentage points; 95% CI, -8.7 to -1.9; P = 0.003). CONCLUSIONS: Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04401579.).
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Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Antivirales/uso terapéutico , Azetidinas/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Purinas/uso terapéutico , Pirazoles/uso terapéutico , Sulfonamidas/uso terapéutico , Adenosina Monofosfato/efectos adversos , Adenosina Monofosfato/uso terapéutico , Adulto , Anciano , Alanina/efectos adversos , Alanina/uso terapéutico , Antivirales/efectos adversos , Azetidinas/efectos adversos , COVID-19/mortalidad , COVID-19/terapia , Método Doble Ciego , Quimioterapia Combinada , Femenino , Mortalidad Hospitalaria , Hospitalización , Humanos , Inhibidores de las Cinasas Janus/efectos adversos , Inhibidores de las Cinasas Janus/uso terapéutico , Masculino , Persona de Mediana Edad , Terapia por Inhalación de Oxígeno , Purinas/efectos adversos , Pirazoles/efectos adversos , Respiración Artificial , Sulfonamidas/efectos adversos , Resultado del TratamientoRESUMEN
This scoping review sought to identify and describe the state of academic faculty development programs in hospital medicine and other specialties. We reviewed faculty development content, structure, metrics of success including facilitators, barriers, and sustainability to create a framework and inform hospital medicine leadership and faculty development initiatives. We completed a systematic search of peer-reviewed literature and searched Ovid MEDLINE ALL (1946 to June 17, 2021) and Embase (via Elsevier, 1947 to June 17, 2021). Twenty-two studies were included in the final review, with wide heterogeneity in program design, program description, outcomes, and study design. Program design included a combination of didactics, workshops, and community or networking events; half of the studies included mentorship or coaching for faculty. Thirteen studies included program description and institutional experience without reported outcomes while eight studies included quantitative analysis and mixed methods results. Barriers to program success included limited time and support for faculty attendance, conflicting clinical commitments, and lack of mentor availability. Facilitators included allotted funding and time for faculty participation, formal mentoring and coaching opportunities, and a structured curriculum with focused skill development supporting faculty priorities. We identified heterogeneous historical studies addressing faculty development across highly variable program design, intervention, faculty targeted, and outcomes assessed. Common themes emerged, including the need for program structure and support, aligning areas of skill development with faculty values, and longitudinal mentoring/coaching. Programs require dedicated program leadership, support for faculty time and participation, curricula focused on skills development, and mentoring and sponsorship.
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Medicina Hospitalar , Tutoría , Humanos , Docentes , Tutoría/métodos , Mentores , Desarrollo de Programa , Docentes Médicos/educaciónRESUMEN
BACKGROUND: The COVID-19 standard of care (SOC) evolved rapidly during 2020 and 2021, but its cumulative effect over time is unclear. OBJECTIVE: To evaluate whether recovery and mortality improved as SOC evolved, using data from ACTT (Adaptive COVID-19 Treatment Trial). DESIGN: ACTT is a series of phase 3, randomized, double-blind, placebo-controlled trials that evaluated COVID-19 therapeutics from February 2020 through May 2021. ACTT-1 compared remdesivir plus SOC to placebo plus SOC, and in ACTT-2 and ACTT-3, remdesivir plus SOC was the control group. This post hoc analysis compared recovery and mortality between these comparable sequential cohorts of patients who received remdesivir plus SOC, adjusting for baseline characteristics with propensity score weighting. The analysis was repeated for participants in ACTT-3 and ACTT-4 who received remdesivir plus dexamethasone plus SOC. Trends in SOC that could explain outcome improvements were analyzed. (ClinicalTrials.gov: NCT04280705 [ACTT-1], NCT04401579 [ACTT-2], NCT04492475 [ACTT-3], and NCT04640168 [ACTT-4]). SETTING: 94 hospitals in 10 countries (86% U.S. participants). PARTICIPANTS: Adults hospitalized with COVID-19. INTERVENTION: SOC. MEASUREMENTS: 28-day mortality and recovery. RESULTS: Although outcomes were better in ACTT-2 than in ACTT-1, adjusted hazard ratios (HRs) were close to 1 (HR for recovery, 1.04 [95% CI, 0.92 to 1.17]; HR for mortality, 0.90 [CI, 0.56 to 1.40]). Comparable patients were less likely to be intubated in ACTT-2 than in ACTT-1 (odds ratio, 0.75 [CI, 0.53 to 0.97]), and hydroxychloroquine use decreased. Outcomes improved from ACTT-2 to ACTT-3 (HR for recovery, 1.43 [CI, 1.24 to 1.64]; HR for mortality, 0.45 [CI, 0.21 to 0.97]). Potential explanatory factors (SOC trends, case surges, and variant trends) were similar between ACTT-2 and ACTT-3, except for increased dexamethasone use (11% to 77%). Outcomes were similar in ACTT-3 and ACTT-4. Antibiotic use decreased gradually across all stages. LIMITATION: Unmeasured confounding. CONCLUSION: Changes in patient composition explained improved outcomes from ACTT-1 to ACTT-2 but not from ACTT-2 to ACTT-3, suggesting improved SOC. These results support excluding nonconcurrent controls from analysis of platform trials in rapidly changing therapeutic areas. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases.
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Antivirales , Tratamiento Farmacológico de COVID-19 , Adulto , Humanos , Antivirales/uso terapéutico , Ensayos Clínicos Fase III como Asunto , Dexametasona , Método Doble Ciego , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
The aim of our laboratory-based study was to investigate the extent of delayed-onset cell death after cryopreservation in endothelial and epithelial cell lines of ovarian origin. We found differences in percentages of vital cells directly after warming and after cultivation for 48 to 72 h. A granulosa cell line of endothelial origin (KGN) and an epithelial cell line (OvCar-3) were used. In both DMSO-containing and DMSO-free protocols, significant differences in vitality rates between the different cell lines when using open and closed vitrification could be shown (DMSO-containing: KGN open vs. OvCar open, p = 0.001; KGN closed vs. OvCar closed, p = 0.001; DMSO-free: KGN open vs. OvCar open, p = 0.001; KGN closed vs. OvCar closed, p = 0.031). Furthermore, there was a marked difference in the percentage of vital cells immediately after warming and after cultivation for 48 to 72 h; whereas the KGN cell line showed a loss of cell viability of 41% using a DMSO-containing protocol, the OvCar-3 cell loss was only 11% after cultivation. Using a DMSO-free protocol, the percentages of late-onset cell death were 77% and 48% for KGN and OvCar-3 cells, respectively. Our data support the hypothesis that cryopreservation-induced damage is cell type and cryoprotective agent dependent.
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Apoptosis , Neoplasias Ováricas , Femenino , Humanos , Línea Celular Tumoral , Criopreservación/métodos , Crioprotectores/farmacología , Células de la Granulosa , Dimetilsulfóxido/farmacologíaRESUMEN
BACKGROUND: The Adaptive Coronavirus Disease 2019 (COVID-19) Treatment Trial-1 (ACTT-1) found that remdesivir therapy hastened recovery in patients hospitalized with COVID-19, but the pathway for this improvement was not explored. We investigated how the dynamics of clinical progression changed along 4 pathways: recovery, improvement in respiratory therapy requirement, deterioration in respiratory therapy requirement, and death. METHODS: We analyzed trajectories of daily ordinal severity scores reflecting oxygen requirements of 1051 patients hospitalized with COVID-19 who participated in ACTT-1. We developed competing risks models that estimate the effect of remdesivir therapy on cumulative incidence of clinical improvement and deterioration, and multistate models that utilize the entirety of each patient's clinical course to characterize the effect of remdesivir on progression along the 4 pathways above. RESULTS: Based on a competing risks analysis, remdesivir reduced clinical deterioration (hazard ratio [HR], 0.73; 95% confidence interval [CI]: .59-.91) and increased clinical improvement (HR, 1.22; 95% CI: 1.08, 1.39) relative to baseline. Our multistate models indicate that remdesivir inhibits worsening to ordinal scores of greater clinical severity among patients on room air or low-flow oxygen (HR, 0.74; 95% CI: .57-.94) and among patients receiving mechanical ventilation or high-flow oxygen/noninvasive positive-pressure ventilation (HR, 0.73; 95% CI: .53-1.00) at baseline. We also find that remdesivir reduces expected intensive care respiratory therapy utilization among patients not mechanically ventilated at baseline. CONCLUSIONS: Remdesivir speeds time to recovery by preventing worsening to clinical states that would extend the course of hospitalization and increase intensive respiratory support, thereby reducing the overall demand for hospital care.
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Tratamiento Farmacológico de COVID-19 , Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Antivirales , Cuidados Críticos , Humanos , Oxígeno , SARS-CoV-2RESUMEN
The Sudan virus disease outbreak in 2022 prompted the Denver Health High-Risk Infection Team (HITeam) to evaluate and implement novel strategies to respond to viral hemorrhagic fever (VHF) events. To improve the VHF response, HITeam members developed a virtual assessment model (VAM) for at-home evaluation of individuals who are suspected of having a VHF. The VAM incorporates aspects of care that would normally be rendered in a high-level isolation unit-including assessment and monitoring, specimen collection, provider consultation, patient and family teaching, and pharmaceutical intervention-into a mobile framework in which team members respond to a suspected case at the individual's home. Building this capability allows for more thorough assessment of a suspect case in the field, as well as the postponement of a decision about activation of the high-level isolation unit until more information is available. Development, testing, and implementation of the VAM required input from an interdisciplinary group of partners that demonstrated the ability of nurses, physicians, laboratorians, paramedics, emergency medical technicians, and public health personnel to integrate into 1 cohesive care team. The resulting model recenters VHF care on the patient by allowing the care team to gather critical information in an environment that is more comfortable for the suspect case while keeping communities safe and lowering exposure risks. The VAM has long-term sustainability implications for global VHF programs and provides solutions for broader challenges in healthcare by modeling cost-effective, patient-centered care within the highly nuanced subspecialty of special pathogen care.
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BACKGROUND: Current standard medications for the treatment of allergic inflammation consist primarily of glucocorticoids and anti-histamines, but adverse side effects or insufficient responsiveness by patient subpopulations illustrate the need for safe and novel alternatives. Thus, there is a demand to develop a porcine model that is able to mimic mast cell-mediated type I hypersensitivity. Previously, we found that escin, a pharmacologically active mix of triterpene saponins from horse chestnut extracts, exerts anti-allergic effects in murine models and merits further investigation as an anti-allergic therapeutic. METHODS: We developed a new porcine model of allergic dermatitis based on a clinical prick test protocol. Histamine clearly provoked erythema and swelling at the prick site, whereas the mast cell-degranulating compound 48/80 even more pronounced caused wheal and flare reactions known from the human prick response. This model was used to test the anti-allergic efficacy of orally applied escin. RESULTS: Oral pretreatment of animals with escin strongly inhibited the allergic skin response induced by compound 48/80 in a dose-dependent manner. Additional in vitro data from murine mast cells indicate an engagement of the glucocorticoid receptor pathway upon treatment with escin. CONCLUSIONS: This model provides a valuable and easy-to-set-up tool for preclinical studies of mast cell-inhibiting compounds. The successful implementation of this model supports the development of oral escin applications as a novel anti-allergic therapy.
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Antialérgicos/farmacología , Dermatitis Atópica/tratamiento farmacológico , Escina/farmacología , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta Inmunológica , Femenino , Histamina/inmunología , Masculino , Pruebas Cutáneas , Porcinos , p-Metoxi-N-metilfenetilamina/farmacologíaRESUMEN
High-level isolation units (HLIUs) are specially designed facilities for care and management of patients with suspected or confirmed high-consequence infectious diseases (HCIDs), equipped with unique infrastructure and operational features. While individual HLIUs have published on their experiences caring for patients with HCIDs and two previous HLIU consensus efforts have outlined key components of HLIUs, we aimed to summarise the existing literature that describes best practices, challenges and core features of these specialised facilities. A narrative review of the literature was conducted using keywords associated with HLIUs and HCIDs. A total of 100 articles were used throughout the manuscript from the literature search or from alternate methods like reference checks or snowballing. Articles were sorted into categories (eg, physical infrastructure, laboratory, internal transport); for each category, a synthesis of the relevant literature was conducted to describe best practices, experiences and operational features. The review and summary of HLIU experiences, best practices, challenges and components can serve as a resource for units continuing to improve readiness, or for hospitals in early stages of developing their HLIU teams and planning or constructing their units. The COVID-19 pandemic, a global outbreak of mpox, sporadic cases of viral haemorrhagic fevers in Europe and the USA, and recent outbreaks of Lassa fever, Sudan Ebolavirus, and Marburg emphasise the need for an extensive summary of HLIU practices to inform readiness and response.
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COVID-19 , Enfermedades Transmisibles , Fiebres Hemorrágicas Virales , Humanos , Pandemias , COVID-19/epidemiología , Enfermedades Transmisibles/epidemiología , Fiebres Hemorrágicas Virales/epidemiología , Brotes de Enfermedades/prevención & controlRESUMEN
In reproductive medicine, the technique of rapid cooling becomes increasingly important for the preservation of tissue and cells. In order to protect the cells, incubation in different cryopreservation solutions is essential. The speed of the cooling process also makes a pivotal contribution to the success of this method. Using Flourescence Activated Cell Sorting (FACS), we investigated the impact of an open rapid and a closed rapid cooling technique on the vitality of human granulosa cells. Furthermore, we examined effects of the different solutions used for rapid cooling and warming before and after rapid cooling. We found a significant lower proportion of vital cells after rapid cooling compared to untreated controls independently of the technique and the tube size. However, we did not find any significant differences between open and closed rapid cooling. In both, a lower proportion of vital granulosa cells were found after incubation in rapid cooling solution only compared to warming solution only. Our results lend support to the conclusion that the difference of cooling-speed between open and closed rapid cooling is, in our settings, not crucial for the success of the procedure and that cryoprotective agents in the rapid cooling solutions have a higher potential to cause severe cell damage than agents used for warming.
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Criopreservación , Crioprotectores , Supervivencia Celular , Criopreservación/métodos , Crioprotectores/farmacología , Femenino , Citometría de Flujo , Células de la Granulosa , HumanosRESUMEN
Latinx in the USA experience disparities in morbidity and mortality when compared to their non-Hispanic White counterparts. Patient-centered culturally sensitive health care (PC-CSHC) has been deemed a best practice approach to alleviate and eliminate these disparities. However, literature on how Latinx patients perceive their care and what indicators of PC-CSHC may be most related to treatment outcomes is limited. This study collected data from 81 adult Latinx participants who had been admitted to an inpatient care unit to understand the following: (a) their perception of their providers' PC-CSHC in three different areas: Competence/Confidence, Sensitivity/Interpersonal, and Respect/Communication; (b) whether there are differences between English- and Spanish-speaking Latinx patients in their perception of their providers' PC-CSHC; and (c) whether these PC-CSHC indicators were associated to patient satisfaction, patient-provider communication, and therapeutic alliance. Participants were mostly male, older than 55 years of age, and working or lower class, with English as their primary language. Results showed that patients rated their providers' Competence (M = 3.57, SD = .46) higher than both Sensitivity, t(68) = .04, p = .04, (M = 3.49, SD =.54), and Respect, t(53) = 2.765, p = .008, (M = 3.38, SD = .57). English-speaking Latinx were overall less satisfied with their providers than Spanish-speaking Latinx, in particular in their communication. Finally, higher provider cultural sensitivity appears to be a predictor of patient satisfaction, patient-provider communication, and working alliance. Implications for refining provider trainings to treat this vulnerable and understudied (i.e., Latinx) population are discussed.
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Asistencia Sanitaria Culturalmente Competente , Hispánicos o Latinos , Satisfacción del Paciente , Alianza Terapéutica , Adulto , Comunicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Relaciones Médico-PacienteRESUMEN
Background Hospitalists value mentorship and scholarly work, yet often struggle to find time and mentors amid busy clinical workloads. Objective To help catalyze writing for hospitalists nationally, we created a Writing Challenge, where we asked hospitalists to commit to the goal of writing 400 words a day, four days a week, for four weeks. Methods Prospective, programmatic evaluation with daily logs followed by a survey at the completion of the project. The four-week Writing Challenge occurred between June 7 and July 5, 2021. Email invitations to participate in the challenge were disseminated to peer networks, and the challenge was promoted using social media. Participants agreed to attempt to write 400 words per day, four days per week, for four weeks. Results Seventy-four individuals from 28 institutions registered for the Writing Challenge, with 36 (49%) participating in the challenge by logging their writing. Participants wrote an average of 4,372 +/- 4,324 words during the challenge. Sixty-eight percent of the participants reported that their amount of writing increased during the challenge and 50% of the participants stated they planned to publish their work, though many participants (46%) reported struggling to write each day. Conclusions The Writing Challenge is one way to generate increased writing and may result in increased scholarly output for academic hospitalists.
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Botulinum toxin type A (BoNT-A) is a promising alternative for patients suffering from chronic joint pain. The aim of this study was to investigate whether a single injection of BoNT-A would produce adverse effects on clinical parameters and synovial parameters as well as lameness. One randomly selected radiocarpal joint was treated with 50 U of BoNT-A in eight horses, and the contralateral joint received saline solution. All horses received injections at day 0 and were re-evaluated twice daily for 7 days for heart rate (HR), respiratory rate (RR), rectal temperature (RT), mucous membrane color, capillary refill time, intestinal motility, appetite, water intake, defecation, urination, and attitude. At these same time points, joint pain and circumference were assessed. Objective lameness evaluations were performed once daily for 7 days and synovial fluid samples were collected at baseline, post-injection hour (PIH) 24 and PIH 168 and evaluated for synovial fluid parameters. HR and RT remained clinically unaltered, despite oscillations over time (P = .001). The remaining clinical parameters were unaltered by treatment or time (P > .05). Joint pain was not elicited by flexion and palpation in both limbs as well as carpal circumference was not altered (P = .88). Lameness was observed only on saline limbs. Cellular parameters evaluated in synovial fluid samples from both carpi had significantly increased from baseline to PIH 24, decreasing at PIH 168 (P < .05). It was concluded that the injection of 50 U BoNT-A is suggested to be a safe therapy for intra-articular use in horses and must be verified by further investigation.
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Toxinas Botulínicas Tipo A , Enfermedades de los Caballos , Animales , Artralgia/tratamiento farmacológico , Artralgia/veterinaria , Toxinas Botulínicas Tipo A/efectos adversos , Enfermedades de los Caballos/tratamiento farmacológico , Caballos , Inyecciones Intraarticulares/veterinaria , Líquido SinovialRESUMEN
The National Emerging Special Pathogens Training and Education Center (NETEC) was established in 2015 to improve the capabilities of healthcare facilities to provide safe and effective care to patients with Ebola and other special pathogens in the United States. Through NETEC, a collaborative network of 10 Regional Emerging Special Pathogen Treatment Centers (RESPTCs) undertook readiness activities that included potential respiratory pathogens. These preparations, which took place before the COVID-19 pandemic, established a foundation of readiness that enabled RESPTCs to play a pivotal role in the US COVID-19 pandemic response. As initial COVID-19 cases were detected in the United States, RESPTCs provided essential isolation capacity, supplies, and subject matter expertise that allowed for additional time for healthcare systems to prepare. Through the Special Pathogen Research Network, RESPTCs rapidly enrolled patients into early clinical trials. During periods of high community transmission, RESPTCs provided educational, clinical, and logistical support to a wide range of healthcare and nonhealthcare settings. In this article, we describe how NETEC and the RESPTC network leveraged this foundation of special pathogen readiness to strengthen the national healthcare system's response to the COVID-19 pandemic. NETEC and the RESPTC network have proven to be an effective model that can support the national response to future emerging special pathogens.
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COVID-19 , Fiebre Hemorrágica Ebola , Humanos , Control de Infecciones , Pandemias/prevención & control , Aislamiento de Pacientes , Estados Unidos/epidemiologíaRESUMEN
Background: The Adaptive COVID Treatment Trial-2 (ACTT-2) found that baricitinib in combination with remdesivir therapy (BCT) sped recovery in hospitalized coronavirus disease 2019 (COVID-19) patients vs remdesivir monotherapy (RMT). We examined how BCT affected progression throughout hospitalization and utilization of intensive respiratory therapies. Methods: We characterized the clinical trajectories of 891 ACTT-2 participants requiring supplemental oxygen or higher levels of respiratory support at enrollment. We estimated the effect of BCT on cumulative incidence of clinical improvement and deterioration using competing risks models. We developed multistate models to estimate the effect of BCT on clinical improvement and deterioration and on utilization of respiratory therapies. Results: BCT resulted in more linear improvement and lower incidence of clinical deterioration compared with RMT (hazard ratio [HR], 0.74; 95% CI, 0.58 to 0.95). The benefit was pronounced among participants enrolled on high-flow oxygen or noninvasive positive-pressure ventilation. In this group, BCT sped clinical improvement (HR, 1.21; 95% CI, 0.99 to 1.51) while slowing clinical deterioration (HR, 0.71; 95% CI, 0.48 to 1.02), which reduced the expected days in ordinal score (OS) 6 per 100 patients by 74 days (95% CI, -8 to 154 days) and the expected days in OS 7 per 100 patients by 161 days (95% CI, 46 to 291 days) compared with RMT. BCT did not benefit participants who were mechanically ventilated at enrollment. Conclusions: Compared with RMT, BCT reduces the clinical burden and utilization of intensive respiratory therapies for patients requiring low-flow oxygen or noninvasive positive-pressure ventilation compared with RMT and may thereby improve care for this patient population.
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OBJECTIVES: This article is one of a series on acute, severe diseases of humans caused by emerging viruses for which there are no or limited licensed medical countermeasures. We approached this summary on South American Hemorrhagic Fevers (SAHF) from a clinical perspective that focuses on pathogenesis, clinical features, and diagnostics with an emphasis on therapies and vaccines that have demonstrated potential for use in an emergency situation through their evaluation in nonhuman primates (NHPs) and/or in humans. METHODS: A standardized literature review was conducted on the clinical, pathological, vaccine, and treatment factors for SAHF as a group and for each individual virus/disease. RESULTS: We identified 2 treatments and 1 vaccine platform that have demonstrated potential benefit for treating or preventing infection in humans and 4 other potential treatments currently under investigation. CONCLUSION: We provide succinct summaries of these countermeasures to give the busy clinician a head start in reviewing the literature if faced with a patient with South American Hemorrhagic Fever. We also provide links to other authoritative sources of information.