In inpatients with COVID-19, none of remdesivir, hydroxychloroquine, lopinavir, or interferon ß-1a differed from standard care for in-hospital mortality.

SOURCE CITATION: Pan H, Peto R, Henao-Restrepo AM, et al. Repurposed antiviral drugs for Covid-19-interim WHO Solidarity Trial results. N Engl J Med. 2020. [Epub ahead of print.] 33264556.

Advancing patient-centered research practices in a pragmatic patient-level randomized clinical trial: A thematic analysis of stakeholder engagement in Emergency Medicine Palliative Care Access (EMPallA).

BACKGROUND: Involving patient and community stakeholders in clinical trials adds value by ensuring research prioritizes patient goals both in conduct of the study and application of the research. The use of stakeholder committees and their impact on the conduct of a multicenter clinical trial have been underreported clinically and academically. The aim of this study is to describe how Study Advisory Committee (SAC) recommendations were implemented throughout the Emergency Medicine Palliative Care Access (EMPallA) trial. EMPallA is a multi-center, pragmatic two-arm randomized controlled trial (RCT) comparing the effectiveness of nurse-led telephonic case management and specialty, outpatient palliative care of older adults with advanced illness. METHODS: A SAC consisting of 18 individuals, including patients with palliative care experience, members of healthcare organizations, and payers was convened for the EMPallA trial. The SAC engaged in community-based participatory research and assisted in all aspects from study design to dissemination. The SAC met with the research team quarterly and annually from project inception to dissemination. Using meeting notes and recordings we completed a qualitative thematic analysis using an iterative process to develop themes and subthemes to summarize SAC recommendations throughout the project's duration. RESULTS: The SAC convened 16 times between 2017 and 2020. Over the course of the project, the SAC provided 41 unique recommendations. Twenty-six of the 41 (63%) recommendations were adapted into formal Institutional Review Board (IRB) study modifications. Recommendations were coded into four major themes: Scientific, Pragmatic, Resource and Dissemination. A majority of the recommendations were related to either the Scientific (46%) or Pragmatic (29%) themes. Recommendations were not mutually exclusive across three study phases: Preparatory, execution and translational. A vast majority (94%) of the recommendations made were related to the execution phase. Major IRB study modifications were made based on their recommendations including data collection of novel dependent variables and expanding recruitment to Spanish-speaking patients. CONCLUSIONS: Our study provides an example of successful integration of a SAC in the conduct of a pragmatic, multi-center RCT. Future trials should engage with SACs in all study phases to ensure trials are relevant, inclusive, patient-focused, and attentive to gaps between health care and patient and family needs. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT03325985, 10/30/2017.

Clinical research should involve patient and community stakeholder perspectives to make sure the study addresses questions important to the studied population. One way to do this is by creating a group of stakeholders who can advise on the conduct of a study. We assembled a Study Advisory Committee (SAC) for the Emergency Medicine Palliative Care Access (EMPallA) trial. The purpose of this clinical trial is to compare the effectiveness of nurse-led telephonic case management and specialty, outpatient palliative care of older adults with advanced illness. This paper describes how the SACs involvement translated into direct impacts on the EMPallA trial. The trial research team held regular meetings with the SAC throughout the trial process. Their involvement led to many significant changes in the trial, such as  expanding recruitment inclusion criteria (Spanish-speaking patients), and including survey instruments to measure lonelines and caregiver burden. The SAC also devised strategies to overcome patient and caregiver recruitment and retention challenges, including the creation of patient-friendly materials and training for research coordinators. This study provides a successful example of how actively engaging patient and community stakeholders, through committee engagement, can promote patient priorities in all phases of a trial while facilitating patient recruitment and retention.

Authorship representation in global emergency medicine: a bibliometric analysis from 2016 to 2020.

INTRODUCTION: High-income country (HIC) authors are disproportionately represented in authorship bylines compared with those affiliated with low and middle-income countries (LMICs) in global health research. An assessment of authorship representation in the global emergency medicine (GEM) literature is lacking but may inform equitable academic collaborations in this relatively new field. METHODS: We conducted a bibliometric analysis of original research articles reporting studies conducted in LMICs from the annual GEM Literature Review from 2016 to 2020. Data extracted included study topic, journal, study country(s) and region, country income classification, author order, country(s) of authors' affiliations and funding sources. We compared the proportion of authors affiliated with each income bracket using Χ2 analysis. We conducted logistic regression to identify factors associated with first or last authorship affiliated with the study country. RESULTS: There were 14 113 authors in 1751 articles. Nearly half (45.5%) of the articles reported work conducted in lower middle-income countries (MICs), 23.6% in upper MICs, 22.5% in low-income countries (LICs). Authors affiliated with HICs were most represented (40.7%); 26.4% were affiliated with lower MICs, 17.4% with upper MICs, 10.3% with LICs and 5.1% with mixed affiliations. Among single-country studies, those without any local authors (8.7%) were most common among those conducted in LICs (14.4%). Only 31.0% of first authors and 21.3% of last authors were affiliated with LIC study countries. Studies in upper MICs (adjusted OR (aOR) 3.6, 95% CI 2.46 to 5.26) and those funded by the study country (aOR 2.94, 95% CI 2.05 to 4.20) had greater odds of having a local first author. CONCLUSIONS: There were significant disparities in authorship representation. Authors affiliated with HICs more commonly occupied the most prominent authorship positions. Recognising and addressing power imbalances in international, collaborative emergency medicine (EM) research is warranted. Innovative methods are needed to increase funding opportunities and other support for EM researchers in LMICs, particularly in LICs.

Mortality in mechanically ventilated patients with COVID-19: a systematic review.

Introduction: The use of mechanical ventilation associated with acute hypoxemic respiratory failure, the most common complication in critically ill COVID-19 patients, defines a high risk population that requires specific consideration of outcomes and treatment practices.Areas covered: This review evaluates existing information about mortality rates and effectiveness of antiviral, immune-modulating, and anticoagulation treatments in COVID-19 patients who received mechanical ventilation. The mortality rate and follow-up periods in patients receiving mechanical ventilation ranged widely. Antivirals, including remdesivir and convalescent plasma, have shown no definitive mortality benefit in this population despite positive results in other COVID-19 patients. Dexamethasone was associated with an absolute reduction in 28-day mortality by 12.3% (95% CI, 6.3 to 17.6), after adjusting for age. Reduced mortality has been demonstrated with tocilizumab use alongside corticosteroids. Evidence is inconclusive for therapeutic anticoagulation, and further studies are needed to determine the comparative benefit of prophylactic anticoagulation.Expert opinion: Significant variation and high mortality rates in mechanically ventilated patients necessitate more standardized outcome measurements, increased consideration of risk factors to reduce intubation, and improved treatment practices. Anticoagulation and dexamethasone should be incorporated in the treatment of patients receiving invasive mechanical ventilation, while more rigorous studies are required for other potential treatments.

Clinical Presentation, Course, and Risk Factors Associated with Mortality in a Severe Outbreak of COVID-19 in Rhode Island, USA, April-June 2020.

Long-term care facilities (LTCFs) have had a disproportionally high mortality rate due to COVID-19. We describe a rapidly escalating COVID-19 outbreak among 116 LTCF residents in Rhode Island, USA. Overall, 111 (95.6%) residents tested positive and, of these, 48 (43.2%) died. The most common comorbidities were hypertension (84.7%) and cardiovascular disease (84.7%). A small percentage (9%) of residents were asymptomatic, while 33.3% of residents were pre-symptomatic, with progression to symptoms within a median of three days following the positive test. While typical symptoms of fever (80.2%) and cough (43.2%) were prevalent, shortness of breath (14.4%) was rarely found despite common hypoxemia (95.5%). The majority of patients demonstrated atypical symptoms with the most common being loss of appetite (61.3%), lethargy (42.3%), diarrhea (37.8%), and fatigue (32.4%). Many residents had increased agitation (38.7%) and anxiety (5.4%), potentially due to the restriction measures or the underlying mental illness. The fever curve was characterized by an intermittent low-grade fever, often the first presenting symptom. Mortality was associated with a disease course beginning with a loss of appetite and lethargy, as well as one more often involving fever greater than 38 °C, loss of appetite, altered mental status, diarrhea, and respiratory distress. Interestingly, no differences in age or comorbidities were noted between survivors and non-survivors. Taking demographic factors into account, treatment with anticoagulation was still associated with reduced mortality (adjusted OR 0.16; 95% C.I. 0.06-0.39; p < 0.001). Overall, the clinical features of the disease in this population can be subtle and the symptoms are commonly atypical. However, clinical decline among those who did not survive was often rapid with patients expiring within 10 days from disease detection. Further studies are needed to better explain the variability in clinical course of COVID-19 among LTCF residents, specifically the factors affecting mortality, the differences observed in symptom presentation, and rate of clinical decline.