Effect of Androgen Suppression on Clinical Outcomes in Hospitalized Men With COVID-19: The HITCH Randomized Clinical Trial.

Importance: SARS-CoV-2 entry requires the TMPRSS2 cell surface protease. Antiandrogen therapies reduce expression of TMPRSS2. Objective: To determine if temporary androgen suppression induced by degarelix improves clinical outcomes of inpatients hospitalized with COVID-19. Design, Setting, and Participants: The Hormonal Intervention for the Treatment in Veterans With COVID-19 Requiring Hospitalization (HITCH) phase 2, placebo-controlled, double-blind, randomized clinical trial compared efficacy of degarelix plus standard care vs placebo plus standard care on clinical outcomes in men hospitalized with COVID-19 but not requiring invasive mechanical ventilation. Inpatients were enrolled at 14 Department of Veterans Affairs hospitals from July 22, 2020, to April 8, 2021. Data were analyzed from August 9 to October 15, 2021. Interventions: Patients stratified by age, history of hypertension, and disease severity were centrally randomized 2:1 to degarelix, (1-time subcutaneous dose of 240 mg) or a saline placebo. Standard care included but was not limited to supplemental oxygen, antibiotics, vasopressor support, peritoneal dialysis or hemodialysis, intravenous fluids, remdesivir, convalescent plasma, and dexamethasone. Main Outcomes and Measures: The composite primary end point was mortality, ongoing need for hospitalization, or requirement for mechanical ventilation at day 15 after randomization. Secondary end points were time to clinical improvement, inpatient mortality, length of hospitalization, duration of mechanical ventilation, time to achieve a temperature within reference range, maximum severity of COVID-19, and the composite end point at 30 days. Results: The trial was stopped for futility after the planned interim analysis, at which time there were 96 evaluable patients, including 62 patients randomized to the degarelix group and 34 patients in the placebo group, out of 198 initially planned. The median (range) age was 70.5 (48-85) years. Common comorbidities included chronic obstructive pulmonary disorder (15 patients [15.6%]), hypertension (75 patients [78.1%]), cardiovascular disease (27 patients [28.1%]), asthma (12 patients [12.5%]), diabetes (49 patients [51.0%]), and chronic respiratory failure requiring supplemental oxygen at baseline prior to COVID-19 (9 patients [9.4%]). For the primary end point, there was no significant difference between the degarelix and placebo groups (19 patients [30.6%] vs 9 patients [26.5%]; P = .67). Similarly, no differences were observed between degarelix and placebo groups in any secondary end points, including inpatient mortality (11 patients [17.7%] vs 6 patients [17.6%]) or all-cause mortality (11 patients [17.7%] vs 7 patents [20.6%]). There were no differences between degarelix and placebo groups in the overall rates of adverse events (13 patients [21.0%] vs 8 patients [23.5%) and serious adverse events (19 patients [30.6%] vs 13 patients [32.4%]), nor unexpected safety concerns. Conclusions and Relevance: In this randomized clinical trial of androgen suppression vs placebo and usual care for men hospitalized with COVID-19, degarelix did not result in amelioration of COVID-19 severity. Trial Registration: ClinicalTrials.gov Identifier: NCT04397718.

Hormonal intervention for the treatment of veterans with COVID-19 requiring hospitalization (HITCH): a multicenter, phase 2 randomized controlled trial of best supportive care vs best supportive care plus degarelix: study protocol for a randomized controlled trial.

BACKGROUND: Therapeutic targeting of host-cell factors required for SARS-CoV-2 entry is an alternative strategy to ameliorate COVID-19 severity. SARS-CoV-2 entry into lung epithelium requires the TMPRSS2 cell surface protease. Pre-clinical and correlative data in humans suggest that anti-androgenic therapies can reduce the expression of TMPRSS2 on lung epithelium. Accordingly, we hypothesize that therapeutic targeting of androgen receptor signaling via degarelix, a luteinizing hormone-releasing hormone (LHRH) antagonist, will suppress COVID-19 infection and ameliorate symptom severity. METHODS: This is a randomized phase 2, placebo-controlled, double-blind clinical trial in 198 patients to compare efficacy of degarelix plus best supportive care versus placebo plus best supportive care on improving the clinical outcomes of male Veterans who have been hospitalized due to COVID-19. Enrolled patients must have documented infection with SARS-CoV-2 based on a positive reverse transcriptase polymerase chain reaction result performed on a nasopharyngeal swab and have a severity of illness of level 3-5 (hospitalized but not requiring invasive mechanical ventilation). Patients stratified by age, history of hypertension, and severity are centrally randomized 2:1 (degarelix: placebo). The composite primary endpoint is mortality, ongoing need for hospitalization, or requirement for mechanical ventilation at 15 after randomization. Important secondary endpoints include time to clinical improvement, inpatient mortality, length of hospitalization, duration of mechanical ventilation, time to achieve a normal temperature, and the maximum severity of COVID-19 illness. Exploratory analyses aim to assess the association of cytokines, viral load, and various comorbidities with outcome. In addition, TMPRSS2 expression in target tissue and development of anti-viral antibodies will also be investigated. DISCUSSION: In this trial, we repurpose the FDA approved LHRH antagonist degarelix, commonly used for prostate cancer, to suppress TMPRSS2, a host cell surface protease required for SARS-CoV-2 cell entry. The objective is to determine if temporary androgen suppression with a single dose of degarelix improves the clinical outcomes of patients hospitalized due to COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04397718. Registered on May 21, 2020.

From policy to practice: A DNP student perspective.

BACKGROUND: Healthcare's rapid evolution has increased focus on doctoral nursing education and expanded experiential immersion opportunities created through innovative academic-community partnerships. METHODS: A partnership between an academic institution and a state board of nursing was formed to provide two Doctorate of Nursing Practice (DNP) students with a fellowship opportunity to learn health policy, strategy, and systems thinking which culminated in participation in a state-wide collaborative and published report. RESULTS: Practicum experience outcomes consisted of learner comprehension of DNP Essential II as evidenced by attendance at health policy meetings, participation in state-wide Summit planning meetings with community partners and Summit participation, facilitation and follow-up report contribution. CONCLUSIONS: Providing students with a practicum experience based on the DNP essentials promotes a curriculum based on scholarly evidence to assure the DNP will be competent to face current demands in healthcare. Experiential learning provides a framework for the DNP to fulfill curriculum while applying skills learned in a real-world environment.

Drug-Induced Liver Injury in the Setting of Analgesic Use.

No professional society has created guidelines to aid clinicians in the management of analgesics in the setting of hepatic injury. Acetaminophen overdose is the most common cause of acute liver failure in the United States. In the setting of acetaminophen toxicity, N-acetylcysteine remains the standard of care. Other analgesics including nonsteroidal antiinflammatory drugs, opiates, tricyclic antidepressants, and anticonvulsants rarely cause liver injury.

Bootstrapping Your Telehealth Program.

Telehealth is a proven modality to better patient care, reduce health care cost, and increase provider efficiency. This article outlines the necessary steps for starting a telehealth program at a medical center or practice. A review of the current literature and health care-related laws was undertaken to identify the necessary steps and considerations for starting a telehealth program. Bootstrapping a telehealth program starts with the creation of concept and identification of need. Generation of a hotbed of support, from providers and patients, is key in gaining executive interest and idea investment. Development of a defined plan of implementation with the utilization of already available technologic assets facilitates ease of execution. Creation of a televisit platform, a patient portal for enrollment, and dedicated provider time for televisits to occur are the next steps in plan realization. Measuring results of patient satisfaction, number of visits, cost reduction, and scheduled procedures are powerful tools in support of the multifaceted expansion of a telehealth program. The authors believe that telehealth programs are critical to advancing patient care, reduction of costs, and increased productivity in the future of medicine.

Initiating Telehealth in a Complex Organization.

Medicine has been praised for breakthroughs that improve the quality and longevity of human life. In the setting of today's fast-paced, tech-savvy society in combination with increased patient volume entering hospital doors, telemedicine proves an effective tool to enable the industry to adapt to the changing world around us. A review of the current literature and legislative laws was conducted along with knowledge from the experience gathered at starting a telehealth platform at Texas Children's Hospital to find the necessary steps for starting a telehealth program. Through digital platform, telemedicine offers remote delivery of medical services to all parts of the country, urban and rural, while enhancing interprofessional referral patterns in the local setting. Telemedicine sets to preemptively triage and guide patients through their appropriate phases of care all the meanwhile, bringing the patient and physician closer together. This discussion delves into the further added benefits to large hospital systems, breaks down the basics of the technological platform, and addresses current barriers to entry in the telehealth industry. This article serves as an introduction to a series regarding effective implementation of telemedicine into the hospital system.

Surveillance for cancers associated with tobacco use--United States, 1999-2004.

PROBLEM/CONDITION: Tobacco use is the leading preventable cause of disease and premature death in the United States. The 2004 Surgeon General report found convincing evidence for a direct causal relationship between tobacco use and the following cancers: lung and bronchial, laryngeal, oral cavity and pharyngeal, esophageal, stomach, pancreatic, kidney and renal pelvis, urinary bladder, and cervical cancers and acute myelogenous leukemia (AML). This report provides state-level cancer incidence data and recent trends for cancers associated with tobacco use. Because information on tobacco use was not available in the databases of the National Program of Cancer Registries (NPCR) and Surveillance, Epidemiology, and End Results (SEER) program, cases of cancer included in this report might or might not be in persons who used tobacco; however, the cancer types included in this report are those defined by the U.S. Surgeon General as having a direct causal relationship with tobacco use (i.e., referred to as tobacco-related cancer in this report). These data are important for initiation, monitoring, and evaluation of targeted tobacco prevention and control measures. REPORTING PERIOD COVERED: 1999--2004. DESCRIPTION OF SYSTEMS: Data were obtained from cancer registries affiliated with CDC's NPCR and the National Cancer Institute's SEER program; combined, these data cover approximately 92% of the U.S. population. Combined data from the NPCR and SEER programs provide the best source of information on population-based cancer incidence for the nation and are the only source of information for 41 states (including the District of Columbia) with cancer surveillance programs that are funded solely by NPCR. This report provides age-adjusted cancer incidence rates by demographic and geographic characteristics, percentage distributions for tumor characteristics, and trends in cancer incidence by sex. RESULTS: Approximately 2.4 million cases of tobacco-related cancer were diagnosed during 1999--2004. Age-adjusted incidence rates ranged from 4.0 per 100,000 persons (for AML) to 69.4 (for lung and bronchial cancer). High rates occurred among men, black and non-Hispanic populations, and older adults. Higher incidence rates of lung and laryngeal cancer occurred in the South compared with other regions, particularly the West, consistent with high smoking patterns in the South. INTERPRETATION: The high rates of tobacco-related cancer observed among men, blacks, non-Hispanics, and older adults reflect overall demographic patterns of cancer incidence in the United States and reflect patterns of tobacco use. PUBLIC HEALTH ACTION: The findings in this report emphasize the need for ongoing surveillance and reporting to monitor cancer incidence trends, identify populations at greatest risk for developing cancer related to tobacco use, and evaluate the effectiveness of targeted tobacco control programs and policies.