Developing a Rapid Response Single IRB Model for Conducting Research During a Public Health Emergency.

Research is foundational for evidence-based management of patients. Clinical research, however, takes time to plan, conduct, and disseminate-a luxury that is rarely available during a public health emergency. The University of Nebraska Medical Center (UNMC) developed a single institutional review board (IRB), with a vision to establish a rapid review resource for a network focused on clinical research of emerging pathogens in the United States. A core aspect of successful initiation of research during a pandemic or epidemic is the ability to operationalize an approach for rapid ethical review of human subject research and conduct those reviews at multiple sites-without losing any of the substantive aspects of ethics review. This process must be cultivated in anticipation of a public health emergency. US guidance for operationalizing IRB review for multisite research in a public health emergency is not well studied and processes are not well established. UNMC sought to address operational gaps and identify the unique procedural needs of rapid response single IRB (RR-sIRB) review of multisite research by conducting a series of preparedness exercises to develop and test the RR-sIRB model. For decades, emergency responder, healthcare, and public health organizations have conducted emergency preparedness exercises to test requirements for emergency response. In this article, we describe 2 types of simulation exercises conducted by UNMC: workshops and tabletops. This effort represents a unique use of emergency preparedness exercises to develop, refine, and test rapid review functions for an sIRB and to validate readiness of regulatory research processes. Such processes are crucial for conducting rapid, ethical, and sound clinical research in public health emergencies.

COVID-19 infection differences among people with disabilities.

Purpose: People with disabilities may be at higher risk for COVID-19 infection and death as a result of their impairments and/or medical conditions, and systemic inequities and disadvantages. People with disabilities are also a very heterogenous group, with many people with disabilities being multiply marginalized. The aim of this study was to examine differences in COVID-19 diagnosis and vaccination between people with and without disabilities, and to explore sociodemographic differences in COVID-19 diagnosis and vaccination among the disability community itself. Methods: To do so, we analyzed secondary United States Census Bureau data from 444,422 people (52,890 adults with disabilities and 391,532 adults without disabilities) about COVID-19 diagnosis, vaccination, and sociodemographics. Frequency person-weights were applied. Results: In this study, 19.3% of adults with disabilities were diagnosed with COVID-19 during the pandemic compared to 16.7% of adults without disabilities. People with disabilities were 1.20 times more likely to be diagnosed with COVID-19 than adults without disabilities. Among people with disabilities, the following groups were more likely to be diagnosed with COVID-19: people with cognitive disabilities; cisgender women; Black people; Hispanic people; people with some college or associate's degrees; people with employer and/or private insurance; and people who lived in larger households. There was not a significant difference in vaccination between people with and without disabilities; however, there were vaccination disparities among the disability community. Conclusions: Many of the people with disabilities who were more likely to face health care disparities prior to the pandemic were also more likely to be diagnosed with COVID-19 during the pandemic.

Jordanian nurses' attitudes toward using electronic health records during COVID-19 pandemic.

Electronic health records (EHRs) have proven their effectiveness during the coronavirus disease (COVID-19) pandemic. However, successful implementation of EHRs requires assessing nurses' attitudes as they are considered the first line in providing direct care for patients. This study assessed Jordanian nurses' attitudes and examined factors that affect nurses' attitudes toward using EHRs. A cross-sectional, correlational design was used. A convenient sample of 130 nurses was recruited from three major public hospitals in Jordan. All Participants completed the Nurses' attitudes Towards Computerization (NATC) Questionnaire. The overall nurses' attitude was positive; the mean was 61.85 (SD = 10.97). Findings revealed no significant relationship between nurses' attitudes toward using EHRs and nurses' age, gender, education level, previous computer skills experience, years of work experience, and years of dealing with EHRs. However, the work unit was found to have a significant correlation with nurses' attitudes toward using EHRs. Therefore, nurse administrators should arrange for the conduct of educational workshops and continuous training programs considering the needs of the nurses.

Endobronchial blood-patch: A novel technique for a persistent pleural air leak.

Introduction: Patients with severe COVID-19 Pneumonia requiring prolonged mechanical ventilation have an increased incidence of pneumothorax. Mechanically ventilated patients who are critically ill and develop a persistent air leak from pneumothorax are poor candidates for surgical repair. As the persistent air leak can be a significant barrier to vent-weaning and clinical stability, these patients present a unique clinical challenge. Clinical case: A 65-year-old male intubated and on prolonged mechanical ventilation for severe COVID-19 Pneumonia developed a pneumothorax complicated by a persistent alveolar-pleural fistula with a persistent air-leak. Given his critical state with ongoing pressor requirements and elevated vent requirements, surgical repair was not an option. A bedside bronchoscopy occlusion study with isolation of the air leak, and subsequent autologous endobronchial blood-patch repair with thrombin was performed with rapid and definitive resolution of the air leak. The patient progressed favorably, ultimately being weaned from the ventilator, decannulated, and walking out of the hospital. Conclusion: In critically ill ventilated patients with pneumothorax complicated by a persistent air-leak, bedside endobronchial evaluation and blood-patch repair is a feasible approach to management.

From paper to screen: regulatory and operational considerations for modernizing the informed consent process.

Electronic platforms provide an opportunity to improve the informed consent (IC) process by permitting elements shown to increase research participant understanding and satisfaction, such as graphics, self-pacing, meaningful engagement, and access to additional information on demand. However, including these elements can pose operational and regulatory challenges for study teams and institutional review boards (IRBs) responsible for the ethical conduct and oversight of research. We examined the experience of two study teams at Alzheimer's Disease Research Centers who chose to move from a paper-based IC process to an electronic informed consent (eIC) process to highlight some of these complexities and explore how IRBs and study teams can navigate them. Here, we identify the key regulations that should be considered when developing and using an eIC process as well as some of the operational considerations eIC presents related to IRB review and how they can be addressed.

Development and validation of a paper spray mass spectrometry method for the rapid quantitation of remdesivir and its active metabolite, GS-441524, in human plasma.

Introduction: Remdesivir (GS-5734) is a nucleoside analog prodrug with antiviral activity against several single-stranded RNA viruses, including the novel severe respiratory distress syndrome virus 2 (SARS-CoV-2). It is currently the only FDA-approved antiviral agent for the treatment of individuals with COVID-19 caused by SARS-CoV-2. However, remdesivir pharmacokinetics/pharmacodynamics (PK/PD) and toxicity data in humans are extremely limited. It is imperative that precise analytical methods for the quantification of remdesivir and its active metabolite, GS-441524, are developed for use in further studies. We report, herein, the first validated anti-viral paper spray-mass spectrometry (PS-MS/MS) assay for the quantification of remdesivir and GS-441524 in human plasma. We seek to highlight the utility of PS-MS/MS technology and automation advancements for its potential future use in clinical research and the clinical laboratory setting. Methods: Calibration curves for remdesivir and GS-441524 were created utilizing seven plasma-based calibrants of varying concentrations and two isotopic internal standards of set concentrations. Four plasma-based quality controls were prepared in a similar fashion to the calibrants and utilized for validation. No sample preparation was needed. Briefly, plasma samples were spotted on a paper substrate contained within pre-manufactured plastic cassette plates, and the spots were dried for 1 h. The samples were then analyzed directly for 1.2 min utilizing PS-MS/MS. All experiments were performed on a Thermo Scientific Altis triple quadrupole mass spectrometer utilizing automated technology. Results: The calibration ranges were 20 - 5000 and 100 - 25000 ng/mL for remdesivir and GS-441524, respectively. The calibration curves for the two antiviral agents showed excellent linearity (average R2 = 0.99-1.00). The inter- and intra-day precision (%CV) across validation runs at four QC levels for both analytes was less than 11.2% and accuracy (%bias) was within ± 15%. Plasma calibrant stability was assessed and degradation for the 4 °C and room temperature samples were seen beginning at Day 7. The plasma calibrants were stable at -20 °C. No interference, matrix effects, or carryover was discovered during the validation process. Conclusions: PS-MS/MS represents a useful methodology for rapidly quantifying remdesivir and GS-441524, which may be useful for clinical PK/PD, therapeutic drug monitoring (TDM), and toxicity assessment, particularly during the current COVID-19 pandemic and future viral outbreaks.

Exploring the potential of delivering mental health care services using digital technologies in Bangladesh: A qualitative analysis.

Background: Bangladesh is a lower-middle-income country affected by a severe lack of mental health service availability due to a scarcity of mental health experts, limited mental health literacy, and community stigma. In other low and middle-income countries, the online provision of mental health care services has addressed issues affecting service availability, accessibility, mass awareness of services, and stigma. Objective: The current study sought to understand stakeholders' perceptions of the potential of digital media-based mental health care delivery in strengthening Bangladesh's mental health system. Method: Online in-depth interviews were conducted with seven psychiatrists and eleven people with lived experiences of mental health issues. In addition, two online focus groups were conducted with ten psychologists and nine mental health entrepreneurs. A thematic analysis of the audio transcriptions was used to identify themes. Result: Stakeholders perceived that the benefits of digital media-based mental health services included the potential of increasing the awareness, availability, and accessibility of mental health services. Participants recommended: the rehabilitation of existing pathways; the use of social media to raise awareness; and the implementation of strategies that integrate different digital-based services to strengthen the mental health system and foster positive mental health-seeking behaviors. Conclusion: Growing mental health awareness, combined with the appropriate use of digital media as a platform for distributing information and offering mental services, can help to promote mental health care. To strengthen mental health services in Bangladesh, tailored services, increased network coverage, and training are required on digital mental health.

COVID-Related Stress and Work Intentions in a Sample of US Health Care Workers.

OBJECTIVE: To evaluate relationships between coronavirus disease 2019 (COVID-19)-related stress and work intentions in a sample of US health care workers. PATIENTS AND METHODS: Between July 1 and December 31, 2020, health care workers were surveyed for fear of viral exposure or transmission, COVID-19-related anxiety or depression, work overload, burnout, and intentions to reduce hours or leave their jobs. RESULTS: Among 20,665 respondents at 124 institutions (median organizational response rate, 34%), intention to reduce hours was highest among nurses (33.7%; n=776), physicians (31.4%; n=2914), and advanced practice providers (APPs; 28.9%; n=608) while lowest among clerical staff (13.6%; n=242) and administrators (6.8%; n=50; all P<.001). Burnout (odds ratio [OR], 2.15; 95% CI, 1.93 to 2.38), fear of exposure, COVID-19-related anxiety/depression, and workload were independently related to intent to reduce work hours within 12 months (all P<.01). Intention to leave one's practice within 2 years was highest among nurses (40.0%; n=921), APPs (33.0%; n=694), other clinical staff (29.4%; n=718), and physicians (23.8%; n=2204) while lowest among administrators (12.6%; n=93; all P<.001). Burnout (OR, 2.57; 95% CI, 2.29 to 2.88), fear of exposure, COVID-19-related anxiety/depression, and workload were predictors of intent to leave. Feeling valued by one's organization was protective of reducing hours (OR, 0.65; 95% CI, 0.59 to 0.72) and intending to leave (OR, 0.40; 95% CI, 0.36 to 0.45; all P<.01). CONCLUSION: Approximately 1 in 3 physicians, APPs, and nurses surveyed intend to reduce work hours. One in 5 physicians and 2 in 5 nurses intend to leave their practice altogether. Reducing burnout and improving a sense of feeling valued may allow health care organizations to better maintain their workforces postpandemic.

The use of dietary supplements for mental health among the Saudi population: A cross-sectional survey.

Introduction: Despite limited evidence about the efficacy and safety of dietary supplements (DSs) for improving mental health, people with or without mental disorders often tend to use them, especially during the ongoing COVID-19 pandemic. Previous studies focused on DS use for maintaining or improving overall health; Therefore, this study aimed to assess the prevalence of DSs for mental health among the SA population and to determine the factors that affect their use. Methods: This cross-sectional study was based on an online survey of Saudi Arabian participants between July and August 2021 with an anonymous, self-completed questionnaire distributed using convenience sampling. The questionnaire included queries related to demographic information, DS use assessment, and mental health evaluation using the Patient Health Questionnaire (PHQ-9), the Generalized Anxiety Disorder 7-item (GAD-7), questionnaire, and the Insomnia Severity Index (ISI). Results: In total, 443 participants from various regions of Saudi Arabia completed the questionnaire. The prevalence of DS use in the Saudi population was 44%. Vitamin D (28%) and melatonin (20%) were the most commonly reported DSs used for mental health. The odds of DS use were three times higher in responders with previous mental health diagnoses (OR: 2.972; 95% CI: 1.602-5.515). Furthermore, the chances of using DSs almost doubled in patients with sub-threshold and moderate to severe insomnia (OR: 1.930; 95% CI: 1.191-3.126 and OR: 2.485; 95% CI: 1.247-4.954, respectively). Conclusion: Responders diagnosed by a specialist with psychiatric disorders or current insomnia had a higher chance of using DSs. Thus, healthcare providers must provide evidence-based information regarding DSs for mental health improvement and encourage the public to consult healthcare professionals before self-medicating for mental health problems.

Echocardiographic predictors of mortality and morbidity in COVID-19 disease using focused cardiovascular ultrasound.

BACKGROUND: Focused transthoracic echocardiography (fTTE) has emerged as a critical diagnostic tool during the COVID-19 pandemic, allowing for efficient cardiac imaging while minimizing staff exposure. The utility of fTTE in predicting clinical outcomes in COVID-19 remains under investigation. METHODS: We conducted a retrospective study of 2,266 hospitalized patients at Rush University Medical Center with COVID-19 infection between March and November 2020 who received a fTTE. fTTE data were analyzed for association with primary adverse outcomes (60-day mortality) and with secondary adverse outcomes (need for renal replacement therapy, need for invasive ventilation, shock, and venous thromboembolism). RESULTS: Of the 427 hospitalized patients who had a fTTE performed (mean 62 years, 43% female), 109 (26%) had died by 60 days. Among patients with an available fTTE measurement, right ventricular (RV) dilation was noted in 34% (106/309), 43% (166/386) had RV dysfunction, and 17% (72/421) had left ventricular (LV) dysfunction. In multivariable models accounting for fTTE data, RV dilation was significantly associated with 60-day mortality (OR 1.93 [CI 1.13-3.3], p = 0.016). LV dysfunction was not significantly associated with 60-day mortality (OR 0.95 [CI: 0.51-1.78], p = 0.87). CONCLUSIONS: Abnormalities in RV echocardiographic parameters are adverse prognosticators in COVID-19 disease. Patients with RV dilation experienced double the risk for 60-day mortality due to COVID-19. To our knowledge, this is the largest study to date that highlights the adverse prognostic implications of RV dilation as determined through fTTE in hospitalized COVID-19 patients.

EVENTS REPORTED ABOUT IRB BRASIL RESSEGUROS S.A. AND THE EFFECTS ON ITS VALUATION

The manuscript has the purpose to develop knowledge and illustrate the discussion of events related to the impacts of accounting practices, reported information and the Covid19 on a company's valuation, the IRB Resseguros, seeking to improve the critical sense about mistakes and successes carried out by companies and that influence their valuation. Through an exploratory study and presented as a teaching case, which allows greater significance for the student's learning process, reports that between the public offering of shares - IPO (2017) and the end of 2019, the IRB's shares reached rise 337%, but in May 2020 the shares fell below their IPO. Concomitant to the economic effects of Covid-19, an investment manager company presented a letter questioning accounting practices and indicating that the profitability of the business would be much lower than known, in addition to other adverse events. For the IRB, the claims about performance would reveal a simple "accounting loss", arising from the rise in the dollar caused by Covid-19 and the consequent economic downturn. The teaching case presents discussions that contribute to the systemic assessment of the impacts of events on organizations and their valuation. The IRB case discusses assumptions involved in the company valuation process;therefore, it considers contingency events, sectorial, macroeconomic peculiarities, strategic decisions, administrative and financial reports, and news about the company. This case contributes to practical discussions in the context of investors, the capital market and company valuation.

Lessons Learned: Beta-Testing the Digital Health Checklist for Researchers Prompts a Call to Action by Behavioral Scientists.

Digital technologies offer unique opportunities for health research. For example, Twitter posts can support public health surveillance to identify outbreaks (eg, influenza and COVID-19), and a wearable fitness tracker can provide real-time data collection to assess the effectiveness of a behavior change intervention. With these opportunities, it is necessary to consider the potential risks and benefits to research participants when using digital tools or strategies. Researchers need to be involved in the risk assessment process, as many tools in the marketplace (eg, wellness apps, fitness sensors) are underregulated. However, there is little guidance to assist researchers and institutional review boards in their evaluation of digital tools for research purposes. To address this gap, the Digital Health Checklist for Researchers (DHC-R) was developed as a decision support tool. A participatory research approach involving a group of behavioral scientists was used to inform DHC-R development. Scientists beta-tested the checklist by retrospectively evaluating the technologies they had chosen for use in their research. This paper describes the lessons learned because of their involvement in the beta-testing process and concludes with recommendations for how the DHC-R could be useful for a variety of digital health stakeholders. Recommendations focus on future research and policy development to support research ethics, including the development of best practices to advance safe and responsible digital health research.

Altered toxicological endpoints in humans from common quaternary ammonium compound disinfectant exposure.

Humans are frequently exposed to Quaternary Ammonium Compounds (QACs). QACs are ubiquitously used in medical settings, restaurants, and homes as cleaners and disinfectants. Despite their prevalence, nothing is known about the health effects associated with chronic low-level exposure. Chronic QAC toxicity, only recently identified in mice, resulted in developmental, reproductive, and immune dysfunction. Cell based studies indicate increased inflammation, decreased mitochondrial function, and disruption of cholesterol synthesis. If these findings translate to human toxicity, multiple physiological processes could be affected. This study tested whether QAC concentrations could be detected in the blood of 43 human volunteers, and whether QAC concentrations influenced markers of inflammation, mitochondrial function, and cholesterol synthesis. QAC concentrations were detected in 80 % of study participants. Blood QACs were associated with increase in inflammatory cytokines, decreased mitochondrial function, and disruption of cholesterol homeostasis in a dose dependent manner. This is the first study to measure QACs in human blood, and also the first to demonstrate statistically significant relationships between blood QAC and meaningful health related biomarkers. Additionally, the results are timely in light of the increased QAC disinfectant exposure occurring due to the SARS-CoV-2 pandemic. MAIN FINDINGS: This study found that 80 % of study participants contained QACs in their blood; and that markers of inflammation, mitochondrial function, and sterol homeostasis varied with blood QAC concentration.

Going remote: Implementing digital research methods at an academic medical center during COVID-19.

COVID-19 has forced medical research institutions to conduct clinical research remotely. Here, we describe how a university's mHealth Research Core helped facilitate the shift to remote research during the COVID-19 pandemic. In 2019 (pre-pandemic), we conducted stakeholder interviews and leadership group sessions to identify, create, and implement resources and core functions to support investigator-initiated mHealth research. Between April 2019 and February 2020, we identified four investigator needs: 1) a seminar series on trends in mHealth research, 2) mHealth case consultation services, 3) liaison services with institutional regulatory compliance groups, and 4) online navigation tools for implementation of mHealth methods (e.g., eConsent) and for building partnerships with technology vendors. To date, the mHealth Research Core has held seven seminars, completed 71 case consultations, assisted four COVID-related clinical studies, advised the IRB on shifting to remote research, and widely disseminated eConsent navigation tools. Although pre-pandemic stakeholder and investigator needs led to the creation of the mHealth Research Core, this institutional resource played a critical role in continuing clinical research during the pandemic by assisting investigators in rapidly shifting to remote study methodology.

A snapshot of U.S. IRB review of COVID-19 research in the early pandemic.

BACKGROUND/OBJECTIVE: Along with the greater research enterprise, Institutional Review Boards (IRBs) had to quickly adapt to the COVID-19 pandemic. IRBs had to review and oversee COVID-related research, while navigating strict public health measures and a workforce largely relegated to working from home. Our objectives were to measure adjustments to standard IRB review processes, IRB turnaround time and document and any novel ethical issues encountered. METHODS: Structured data requests were sent to members of the Consortium to Advance Effective Research Ethics Oversight directing Human Research Protection Programs (HRPP). RESULTS: Fourteen of the 32 HRPP director members responded to a questionnaire about their approach to review and oversight during COVID-19. Eleven of the 14 provided summary data on COVID-19-specific protocols and six of the 11 provided protocol-related documents for our review. All respondents adopted at least one additional COVID-19-specific step to their usual review process. The average turnaround time for convened and expedited IRB reviews was 15 calendar days. In our review of the documents from 194 COVID-19-specific protocols (n = 302 documents), we identified only a single review that raised ethical concerns unique to COVID-19. CONCLUSIONS: Our data provide a snapshot of how HRPPs approached the review of COVID-19-specific protocols at the start of the pandemic in the USA. While not generalizable to all HRPPs, these data indicate that HRPPs can adapt and respond quickly response to a pandemic and likely need little novel expertise in the review and oversight of COVID-19-specific protocols.

Outpatient and inpatient anticoagulation therapy and the risk for hospital admission and death among COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state. Limited data exist informing the relationship between anticoagulation therapy and risk for COVID-19 related hospitalization and mortality. METHODS: We evaluated all patients over the age of 18 diagnosed with COVID-19 in a prospective cohort study from March 4th to August 27th, 2020 among 12 hospitals and 60 clinics of M Health Fairview system (USA). We investigated the relationship between (1) 90-day anticoagulation therapy among outpatients before COVID-19 diagnosis and the risk for hospitalization and mortality and (2) Inpatient anticoagulation therapy and mortality risk. FINDINGS: Of 6195 patients, 598 were immediately hospitalized and 5597 were treated as outpatients. The overall case-fatality rate was 2•8% (n = 175 deaths). Among the patients who were hospitalized, the inpatient mortality was 13%. Among the 5597 COVID-19 patients initially treated as outpatients, 160 (2.9%) were on anticoagulation and 331 were eventually hospitalized (5.9%). In a multivariable analysis, outpatient anticoagulation use was associated with a 43% reduction in risk for hospital admission, HR (95% CI = 0.57, 0.38-0.86), p = 0.007, but was not associated with mortality, HR (95% CI=0.88, 0.50 - 1.52), p = 0.64. Inpatients who were not on anticoagulation (before or after hospitalization) had an increased risk for mortality, HR (95% CI = 2.26, 1.17-4.37), p = 0.015. INTERPRETATION: Outpatients with COVID-19 who were on outpatient anticoagulation at the time of diagnosis experienced a 43% reduced risk of hospitalization. Failure to initiate anticoagulation upon hospitalization or maintaining outpatient anticoagulation in hospitalized COVID-19 patients was associated with increased mortality risk. FUNDING: No funding was obtained for this study.

Building biorepositories in the midst of a pandemic.

Biospecimen repositories play a vital role in enabling investigation of biologic mechanisms, identification of disease-related biomarkers, advances in diagnostic assays, recognition of microbial evolution, and characterization of new therapeutic targets for intervention. They rely on the complex integration of scientific need, regulatory oversight, quality control in collection, processing and tracking, and linkage to robust phenotype information. The COVID-19 pandemic amplified many of these considerations and illuminated new challenges, all while academic health centers were trying to adapt to unprecedented clinical demands and heightened research constraints not witnessed in over 100 years. The outbreak demanded rapid understanding of SARS-CoV-2 to develop diagnostics and therapeutics, prompting the immediate need for access to high quality, well-characterized COVID-19-associated biospecimens. We surveyed 60 Clinical and Translational Science Award (CTSA) hubs to better understand the strategies and barriers encountered in biobanking before and in response to the COVID-19 pandemic. Feedback revealed a major shift in biorepository model, specimen-acquisition and consent process from a combination of investigator-initiated and institutional protocols to an enterprise-serving strategy. CTSA hubs were well equipped to leverage established capacities and expertise to quickly respond to the scientific needs of this crisis through support of institutional approaches in biorepository management.

Status of Institutional Review Board Meetings Conducted Through Web Conference Systems in Japanese National University Hospitals During the COVID-19 Pandemic: Questionnaire Study.

BACKGROUND: With the global proliferation of the novel COVID-19 disease, conventionally conducting institutional review board (IRB) meetings has become a difficult task. Amid concerns about the suspension of drug development due to delays within IRBs, it has been suggested that IRB meetings should be temporarily conducted via the internet. OBJECTIVE: This study aimed to elucidate the current status of IRB meetings conducted through web conference systems. METHODS: A survey on conducting IRB meetings through web conference systems was administered to Japanese national university hospitals. Respondents were in charge of operating IRB offices at different universities. This study was not a randomized controlled trial. RESULTS: The survey was performed at 42 facilities between the end of May and early June, 2020, immediately after the state of emergency was lifted in Japan. The survey yielded a response rate of 74% (31/42). Additionally, while 68% (21/31) of facilities introduced web conference systems for IRB meetings, 13% (4/31) of the surveyed facilities postponed IRB meetings. Therefore, we conducted a further survey of 21 facilities that implemented web conference systems for IRB meetings. According to 71% (15/21) of the respondents, there was no financial burden for implementing these systems, as they were free of charge. In 90% (19/21) of the facilities, IRB meetings through web conference systems were already being conducted with personal electronic devices. Furthermore, in 48% (10/21) of facilities, a web conference system was used in conjunction with face-to-face meetings. CONCLUSIONS: Due to the COVID-19 pandemic, the number of reviews in clinical trial core hospitals has decreased. This suggests that the development of pharmaceuticals has stagnated because of COVID-19. According to 71% (15/21) of the respondents who conducted IRB meetings through web conference systems, the cost of introducing such meetings was US $0, showing a negligible financial burden. Moreover, it was shown that online deliberations could be carried out in the same manner as face-to-face meetings, as 86% (18/21) of facilities stated that the number of comments made by board members did not change. To improve the quality of IRB meetings conducted through web conference systems, it is necessary to further examine camera use and the content displayed on members' screens during meetings. Further examination of all members who use web conference systems is required. Our measures for addressing the requests and problems identified in our study could potentially be considered protocols for future IRB meetings, when the COVID-19 pandemic has passed and face-to-face meetings are possible again. This study also highlights the importance of developing web conference systems for IRB meetings to respond to future unforeseen pandemics.

Tocilizumab for severe COVID-19 related illness - A community academic medical center experience.

The SARS-CoV-2 virus responsible for the COVID-19 pandemic can result in severe or fatal disease in a subset of infected patients. While the pathogenesis of severe COVID-19 disease has yet to be fully elucidated, an overexuberant and harmful immune response to the SARS-CoV-2 virus may be a pivotal aspect of critical illness in this patient population. The inflammatory cytokine, IL-6, has been found to be consistently elevated in severely ill COVID-19 patients, prompting speculation that IL-6 is an important driver of the pathologic process. The inappropriately elevated levels of inflammatory cytokines in COVID-19 patients is similar to cytokine release syndrome (CRS) observed in cell therapy patients. We sought to describe outcomes in a series of severely ill patients with COVID-19 CRS following treatment with anti-IL-6/IL-6-Receptor (anti-IL-6/IL-6-R) therapy, including tocilizumab or siltuximab. At our academic community medical center, we formed a multi-disciplinary committee for selecting severely ill COVID-19 patients for therapy with anti-IL-6 or IL-6-R agents. Key selection criteria included evidence of hyperinflammation, most notably elevated levels of C-reactive protein (CRP) and ferritin, and an increasing oxygen requirement. By the data cutoff point, we treated 31 patients with anti-IL-6/IL-6-R agents including 12 who had already been intubated. Overall, 27 (87%) patients are alive and 24 (77%) have been discharged from the hospital. Clinical responses to anti-IL-6/IL-6-R therapy were accompanied by significant decreases in temperature, oxygen requirement, CRP, IL-6, and IL-10 levels. Based on these data, we believe anti-IL-6/IL-6-R therapy can be effective in managing early CRS related to COVID-19 disease. Further study of anti-IL-6/IL-6-R therapy alone and in combination with other classes of therapeutics is warranted and trials are underway.

Cardiac electrophysiology consultative experience at the epicenter of the COVID-19 pandemic in the United States.

BACKGROUND: The COVID-19 pandemic has greatly altered the practice of cardiac electrophysiology around the world for the foreseeable future. Professional organizations have provided guidance for practitioners, but real-world examples of the consults and responsibilities cardiac electrophysiologists face during a surge of COVID-19 patients is lacking. METHODS: In this observational case series we report on 29 consecutive inpatient electrophysiology consultations at a major academic medical center in New York City, the epicenter of the pandemic in the United States, during a 2 week period from March 30-April 12, 2020, when 80% of hospital beds were occupied by COVID-19 patients, and the New York City metropolitan area accounted for 10% of COVID-19 cases worldwide. RESULTS: Reasons for consultation included: Atrial tachyarrhythmia (31%), cardiac implantable electronic device management (28%), bradycardia (14%), QTc prolongation (10%), ventricular arrhythmia (7%), post-transcatheter aortic valve replacement conduction abnormality (3.5%), ventricular pre-excitation (3.5%), and paroxysmal supraventricular tachycardia (3.5%). Twenty-four patients (86%) were positive for COVID-19 by nasopharyngeal swab. All elective procedures were canceled, and only one urgent device implantation was performed. Thirteen patients (45%) required in-person evaluation and the remainder were managed remotely. CONCLUSION: Our experience shows that the application of a massive alteration in workflow and personnel forced by the pandemic allowed our team to efficiently address the intersection of COVID-19 with a range of electrophysiology issues. This experience will prove useful as guidance for emerging hot spots or areas affected by future waves of the pandemic.