Large Language Model as Unsupervised Health Information Retriever.

Retrieving health information is a task of search for health-related information from a variety of sources. Gathering self-reported health information may help enrich the knowledge body of the disease and its symptoms. We investigated retrieving symptom mentions in COVID-19-related Twitter posts with a pretrained large language model (GPT-3) without providing any examples (zero-shot learning). We introduced a new performance measure of total match (TM) to include exact, partial and semantic matches. Our results show that the zero-shot approach is a powerful method without the need to annotate any data, and it can assist in generating instances for few-shot learning which may achieve better performance.

Renin-Angiotensin System Modulation With Synthetic Angiotensin (1-7) and Angiotensin II Type 1 Receptor-Biased Ligand in Adults With COVID-19: Two Randomized Clinical Trials.

Importance: Preclinical models suggest dysregulation of the renin-angiotensin system (RAS) caused by SARS-CoV-2 infection may increase the relative activity of angiotensin II compared with angiotensin (1-7) and may be an important contributor to COVID-19 pathophysiology. Objective: To evaluate the efficacy and safety of RAS modulation using 2 investigational RAS agents, TXA-127 (synthetic angiotensin [1-7]) and TRV-027 (an angiotensin II type 1 receptor-biased ligand), that are hypothesized to potentiate the action of angiotensin (1-7) and mitigate the action of the angiotensin II. Design, Setting, and Participants: Two randomized clinical trials including adults hospitalized with acute COVID-19 and new-onset hypoxemia were conducted at 35 sites in the US between July 22, 2021, and April 20, 2022; last follow-up visit: July 26, 2022. Interventions: A 0.5-mg/kg intravenous infusion of TXA-127 once daily for 5 days or placebo. A 12-mg/h continuous intravenous infusion of TRV-027 for 5 days or placebo. Main Outcomes and Measures: The primary outcome was oxygen-free days, an ordinal outcome that classifies a patient's status at day 28 based on mortality and duration of supplemental oxygen use; an adjusted odds ratio (OR) greater than 1.0 indicated superiority of the RAS agent vs placebo. A key secondary outcome was 28-day all-cause mortality. Safety outcomes included allergic reaction, new kidney replacement therapy, and hypotension. Results: Both trials met prespecified early stopping criteria for a low probability of efficacy. Of 343 patients in the TXA-127 trial (226 [65.9%] aged 31-64 years, 200 [58.3%] men, 225 [65.6%] White, and 274 [79.9%] not Hispanic), 170 received TXA-127 and 173 received placebo. Of 290 patients in the TRV-027 trial (199 [68.6%] aged 31-64 years, 168 [57.9%] men, 195 [67.2%] White, and 225 [77.6%] not Hispanic), 145 received TRV-027 and 145 received placebo. Compared with placebo, both TXA-127 (unadjusted mean difference, -2.3 [95% CrI, -4.8 to 0.2]; adjusted OR, 0.88 [95% CrI, 0.59 to 1.30]) and TRV-027 (unadjusted mean difference, -2.4 [95% CrI, -5.1 to 0.3]; adjusted OR, 0.74 [95% CrI, 0.48 to 1.13]) resulted in no difference in oxygen-free days. In the TXA-127 trial, 28-day all-cause mortality occurred in 22 of 163 patients (13.5%) in the TXA-127 group vs 22 of 166 patients (13.3%) in the placebo group (adjusted OR, 0.83 [95% CrI, 0.41 to 1.66]). In the TRV-027 trial, 28-day all-cause mortality occurred in 29 of 141 patients (20.6%) in the TRV-027 group vs 18 of 140 patients (12.9%) in the placebo group (adjusted OR, 1.52 [95% CrI, 0.75 to 3.08]). The frequency of the safety outcomes was similar with either TXA-127 or TRV-027 vs placebo. Conclusions and Relevance: In adults with severe COVID-19, RAS modulation (TXA-127 or TRV-027) did not improve oxygen-free days vs placebo. These results do not support the hypotheses that pharmacological interventions that selectively block the angiotensin II type 1 receptor or increase angiotensin (1-7) improve outcomes for patients with severe COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04924660.

Oxygen-Saturation Targets for Critically Ill Adults Receiving Mechanical Ventilation.

BACKGROUND: Invasive mechanical ventilation in critically ill adults involves adjusting the fraction of inspired oxygen to maintain arterial oxygen saturation. The oxygen-saturation target that will optimize clinical outcomes in this patient population remains unknown. METHODS: In a pragmatic, cluster-randomized, cluster-crossover trial conducted in the emergency department and medical intensive care unit at an academic center, we assigned adults who were receiving mechanical ventilation to a lower target for oxygen saturation as measured by pulse oximetry (Spo₂) (90%; goal range, 88 to 92%), an intermediate target (94%; goal range, 92 to 96%), or a higher target (98%; goal range, 96 to 100%). The primary outcome was the number of days alive and free of mechanical ventilation (ventilator-free days) through day 28. The secondary outcome was death by day 28, with data censored at hospital discharge. RESULTS: A total of 2541 patients were included in the primary analysis. The median number of ventilator-free days was 20 (interquartile range, 0 to 25) in the lower-target group, 21 (interquartile range, 0 to 25) in the intermediate-target group, and 21 (interquartile range, 0 to 26) in the higher-target group (P = 0.81). In-hospital death by day 28 occurred in 281 of the 808 patients (34.8%) in the lower-target group, 292 of the 859 patients (34.0%) in the intermediate-target group, and 290 of the 874 patients (33.2%) in the higher-target group. The incidences of cardiac arrest, arrhythmia, myocardial infarction, stroke, and pneumothorax were similar in the three groups. CONCLUSIONS: Among critically ill adults receiving invasive mechanical ventilation, the number of ventilator-free days did not differ among groups in which a lower, intermediate, or higher Spo₂ target was used. (Supported by the National Heart, Lung, and Blood Institute and others; PILOT ClinicalTrials.gov number, NCT03537937.).

Vaccine Refusal: A Preliminary Interdisciplinary Investigation

Many people who generally receive standard recommended inoculations refuse to partake of COVID-19 vaccines, preventatives that are effective, safe, and life-saving amidst the current pandemic. Our quest is to understand this puzzling and dangerous phenomenon, as it exists among US and UK citizens, whom in other respects would be regarded as quite regular. We will discuss Vaccine Refusal compared with two better understood phenomena: addiction, and akrasia, along with the related matters of human action, intention, agency, will, and identity. Vaccine Refusal, we will argue, appears to be rewarded by “informational reinforcement” leading to heightened arousal, along with increases in self-esteem resulting from “bucking the trend,” asserting one's “superior” understanding, and “tribal identity” in acting against social norms. These factors provide an overall reward amounting to satisfaction that outweighs the well-known consequences of COVID-19 infections. Our investigations will also lead us to a pair of epistemological hypotheses about two subtypes of the Vaccine Refusers under consideration here.

REFLECTIVE GROUPS FOR THE REDUCTION OF BURNOUT IN JUNIOR DOCTORS

Background: Junior medical officers (JMOs) are exposed to many stressful experiences during their clinical training, especially during crises such as the COVID-19 pandemic. Research from comparable professions shows that under stress, the ability to think and act flexibly is impaired. This may lead to moral injury and psychological defensiveness leading to a vicious cycle of negative experiences, interpersonal conflict and burnout. Stress Inoculation Therapy (SIT) contextualises and normalises arousal and emotions under acute stress, and Group analysis (GA) promotes reflective skills to reduce interpersonal conflict and chronic stress. Therapist-led reflective groups combining SIT and GA was offered to two cohorts of JMOs in an open-label prospective trial to evaluate feasibility, acceptability and impact on burnout. Objectives: To investigate the acceptability and benefit in well-being, function and reduced burnout, of a weekly reflective group intervention for JMOs. Methods: An initial feasibility trial and exit interview was followed by a before and after study at a regional teaching hospital. All JMOs were invited to participate in weekly reflective groups based on SIT and GA. Groups lasted for 6-12 months and took place either in person or online. Baseline, end-of-treatment and long-term measures of well-being and burnout, followed by an exit interview, were collected for mixed-methods analysis. Findings: A 12-month feasibility trial was completed with six participants and was well tolerated. A second, 6 month, before and after study is underway. Conclusion: Qualitative results support the feasibility and acceptability of reflective groups. Quantitative results are anticipated in mid-2022.

Neutralizing COVID-19 Convalescent Plasma in Adults Hospitalized With COVID-19: A Blinded, Randomized, Placebo-Controlled Trial.

BACKGROUND: Convalescent plasma has been one of the most common treatments for COVID-19, but most clinical trial data to date have not supported its efficacy. RESEARCH QUESTION: Is rigorously selected COVID-19 convalescent plasma with neutralizing anti-SARS-CoV-2 antibodies an efficacious treatment for adults hospitalized with COVID-19? STUDY DESIGN AND METHODS: This was a multicenter, blinded, placebo-controlled randomized clinical trial among adults hospitalized with SARS-CoV-2 infection and acute respiratory symptoms for < 14 days. Enrolled patients were randomly assigned to receive one unit of COVID-19 convalescent plasma (n = 487) or placebo (n = 473). The primary outcome was clinical status (disease severity) 14 days following study infusion measured with a seven-category ordinal scale ranging from discharged from the hospital with resumption of normal activities (lowest score) to death (highest score). The primary outcome was analyzed with a multivariable ordinal regression model, with an adjusted odds ratio (aOR) < 1.0 indicating more favorable outcomes with convalescent plasma than with placebo. In secondary analyses, trial participants were stratified according to the presence of endogenous anti-SARS-CoV-2 antibodies ("serostatus") at randomization. The trial included 13 secondary efficacy outcomes, including 28-day mortality. RESULTS: Among 974 randomized patients, 960 were included in the primary analysis. Clinical status on the ordinal outcome scale at 14 days did not differ between the convalescent plasma and placebo groups in the overall population (aOR, 1.04; one-seventh support interval [1/7 SI], 0.82-1.33), in patients without endogenous antibodies (aOR, 1.15; 1/7 SI, 0.74-1.80), or in patients with endogenous antibodies (aOR, 0.96; 1/7 SI, 0.72-1.30). None of the 13 secondary efficacy outcomes were different between groups. At 28 days, 89 of 482 (18.5%) patients in the convalescent plasma group and 80 of 465 (17.2%) patients in the placebo group had died (aOR, 1.04; 1/7 SI, 0.69-1.58). INTERPRETATION: Among adults hospitalized with COVID-19, including those seronegative for anti-SARS-CoV-2 antibodies, treatment with convalescent plasma did not improve clinical outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04362176; URL: www. CLINICALTRIALS: gov.

The potential of disaster digital archives in disaster education: The case of the Japan disasters digital archive (JDA) and its geo-location functions

Using the Japan Disasters Digital Archive (JDA) as an example, the present study examines how geo-location functions in disaster digital archives may contribute to disaster risk awareness. It focuses on the sites affected by or representing lessons learned from the 2011 Great East Japan Earthquake (GEJE), such as the tsunami inundated coastal areas or museums. The study tests the thesis that geo-located data in digital archives can enhance disaster risk awareness by allowing its users to discover novel location-specific information. The Covid-19 pandemic drastically influenced the research design and the results. The research methods had to be drastically changed from group-based field trips and in-person interviews to virtual research methods that participants could follow on their own. Although there is room for improvements in the JDA design and function, the research results suggest that options for visitors to retrieve information through digital archives on their own while visiting sites of their interest can contribute to their understanding of the history of these specific places and local risks. Promoting self-guided tours by giving access to disaster digital archives with a geolocation-function could also be used as a cost saving option for museums and visitors alike to explore disaster-affected areas, especially in times of a pandemic when visitors are discouraged from joining crowded tours. As a whole, this research aims to not only improve (disaster) digital archives but also to contribute to disaster education in general and offer a widened learning experience for visitors of disaster affected areas in particular.

Discovery of COVID-19 Symptomatic Experience Reported by Twitter Users.

Since the beginning of the COVID-19 pandemic, patients shared their personal experiences of the viral infection on social media. Gathering their symptomatic experiences reported on Twitter may help better understand the infectious disease and supplement our knowledge of the disease gathered by healthcare workers. In this study, we identified personal experience tweets related to COVID-19 infection using a pre-trained and fine-tuned language model, and annotated the machine-identified tweets in order to extract the information of infection status, symptom concepts, and the days the symptomatic experience occurred. Our result shows that the top 10 most common symptoms mentioned in the collected Twitter data are in line with those published by WHO and CDC. The symptoms along with the day information appear to provide additional insight on how the infection progresses in infected individuals.

Securely sharing DSMB reports to speed decision making from multiple, concurrent, independent studies of similar treatments in COVID-19.

Introduction: As clinical trials were rapidly initiated in response to the COVID-19 pandemic, Data and Safety Monitoring Boards (DSMBs) faced unique challenges overseeing trials of therapies never tested in a disease not yet characterized. Traditionally, individual DSMBs do not interact or have the benefit of seeing data from other accruing trials for an aggregated analysis to meaningfully interpret safety signals of similar therapeutics. In response, we developed a compliant DSMB Coordination (DSMBc) framework to allow the DSMB from one study investigating the use of SARS-CoV-2 convalescent plasma to treat COVID-19 to review data from similar ongoing studies for the purpose of safety monitoring. Methods: The DSMBc process included engagement of DSMB chairs and board members, execution of contractual agreements, secure data acquisition, generation of harmonized reports utilizing statistical graphics, and secure report sharing with DSMB members. Detailed process maps, a secure portal for managing DSMB reports, and templates for data sharing and confidentiality agreements were developed. Results: Four trials participated. Data from one trial were successfully harmonized with that of an ongoing trial. Harmonized reports allowing for visualization and drill down into the data were presented to the ongoing trial's DSMB. While DSMB deliberations are confidential, the Chair confirmed successful review of the harmonized report. Conclusion: It is feasible to coordinate DSMB reviews of multiple independent studies of a similar therapeutic in similar patient cohorts. The materials presented mitigate challenges to DSMBc and will help expand these initiatives so DSMBs may make more informed decisions with all available information.

Oxygen-Free Days as an Outcome Measure in Clinical Trials of Therapies for COVID-19 and Other Causes of New-Onset Hypoxemia.

Mortality historically has been the primary outcome of choice for acute and critical care clinical trials. However, undue reliance on mortality can limit the scope of trials that can be performed. Large sample sizes are usually needed for trials powered for a mortality outcome, and focusing solely on mortality fails to recognize the importance that reducing morbidity can have on patients' lives. The COVID-19 pandemic has highlighted the need for rapid, efficient trials to rigorously evaluate new therapies for hospitalized patients with acute lung injury. Oxygen-free days (OFDs) is a novel outcome for clinical trials that is a composite of mortality and duration of new supplemental oxygen use. It is designed to characterize recovery from acute lung injury in populations with a high prevalence of new hypoxemia and supplemental oxygen use. In these populations, OFDs captures two patient-centered consequences of acute lung injury: mortality and hypoxemic lung dysfunction. Power to detect differences in OFDs typically is greater than that for other clinical trial outcomes, such as mortality and ventilator-free days. OFDs is the primary outcome for the Fourth Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-4) Host Tissue platform, which evaluates novel therapies targeting the host response to COVID-19 among adults hospitalized with COVID-19 and new hypoxemia. This article outlines the rationale for use of OFDs as an outcome for clinical trials, proposes a standardized method for defining and analyzing OFDs, and provides a framework for sample size calculations using the OFD outcome.

Assessment of Awake Prone Positioning in Hospitalized Adults With COVID-19: A Nonrandomized Controlled Trial.

Importance: Awake prone positioning may improve hypoxemia among patients with COVID-19, but whether it is associated with improved clinical outcomes remains unknown. Objective: To determine whether the recommendation of awake prone positioning is associated with improved outcomes among patients with COVID-19-related hypoxemia who have not received mechanical ventilation. Design, Setting, and Participants: This pragmatic nonrandomized controlled trial was conducted at 2 academic medical centers (Vanderbilt University Medical Center and NorthShore University HealthSystem) during the COVID-19 pandemic. A total of 501 adult patients with COVID-19-associated hypoxemia who had not received mechanical ventilation were enrolled from May 13 to December 11, 2020. Interventions: Patients were assigned 1:1 to receive either the practitioner-recommended awake prone positioning intervention (intervention group) or usual care (usual care group). Main Outcomes and Measures: Primary outcome analyses were performed using a bayesian proportional odds model with covariate adjustment for clinical severity ranking based on the World Health Organization ordinal outcome scale, which was modified to highlight the worst level of hypoxemia on study day 5. Results: A total of 501 patients (mean [SD] age, 61.0 [15.3] years; 284 [56.7%] were male; and most [417 (83.2%)] were self-reported non-Hispanic or non-Latinx) were included. Baseline severity was comparable between the intervention vs usual care groups, with 170 patients (65.9%) vs 162 patients (66.7%) receiving oxygen via standard low-flow nasal cannula, 71 patients (27.5%) vs 62 patients (25.5%) receiving oxygen via high-flow nasal cannula, and 16 patients (6.2%) vs 19 patients (7.8%) receiving noninvasive positive-pressure ventilation. Nursing observations estimated that patients in the intervention group spent a median of 4.2 hours (IQR, 1.8-6.7 hours) in the prone position per day compared with 0 hours (IQR, 0-0.7 hours) per day in the usual care group. On study day 5, the bayesian posterior probability of the intervention group having worse outcomes than the usual care group on the modified World Health Organization ordinal outcome scale was 0.998 (posterior median adjusted odds ratio [aOR], 1.63; 95% credibility interval [CrI], 1.16-2.31). However, on study days 14 and 28, the posterior probabilities of harm were 0.874 (aOR, 1.29; 95% CrI, 0.84-1.99) and 0.673 (aOR, 1.12; 95% CrI, 0.67-1.86), respectively. Exploratory outcomes (progression to mechanical ventilation, length of stay, and 28-day mortality) did not differ between groups. Conclusions and Relevance: In this nonrandomized controlled trial, prone positioning offered no observed clinical benefit among patients with COVID-19-associated hypoxemia who had not received mechanical ventilation. Moreover, there was substantial evidence of worsened clinical outcomes at study day 5 among patients recommended to receive the awake prone positioning intervention, suggesting potential harm. Trial Registration: ClinicalTrials.gov Identifier: NCT04359797.

Purulent pericarditis can be near fatal

A previously healthy 27 years-old male presented with 2 weeks of substernal chest pain, progressive dyspnea, palpitations, dizziness, and(&) fever. On exam, he had tachypnea & tachycardia, was hypotensive with an elevated JVP & muffled heart sounds. Labs showed elevated WBC, CRP, lactate & high sensitive troponin. Negative for COVID-19, flu. EKG showed sinus tachycardia. CT showed large pericardial effusion with gas in the pericardial space. Echo (Figure 1) revealed large pericardial effusion with tamponade. Emergent pericardiocentesis was performed draining a liter of straw-colored thick fluid (fluid: serum LDH >3) (Figure 2). Cultures grew Strep. Anginosus & Propionibacterium acnes. Extensive infectious & immunological workup returned negative. He had initially improved on broad-spectrum antibiotics however declined clinically on day 5. Repeat CT (Figures 3 & 4) showed recurrent pericardial effusion & mediastinal abscess with trace extravasation of contrast from the esophagus to posterior mediastinum. We present a case of esophageal perforation leading to Pyopneumopericardium. Stephenson et al. reported a case series of 13 patients with esophagopericardial fistulas & pyopneumopericardium with a 100% mortality rate. Another case series showed survival rates of only 17% in 60 patients with pyopneumopericardium secondary to esophageal perforation. Erosion of esophageal ulcers, ingestion of foreign body, iatrogenic, trauma, malignancy, localized inflammation can lead to esophageal perforation. Streptococcus pneumoniae & Staphylococcus aureus are common pathogens involved. Constrictive pericarditis is a possible complication in up to 20 to 30%. Our patient underwent pericardial window & surgical debridement followed by EGD-guided gastro-jejunal tube placement. He did well after 4 weeks of IV antibiotics. Our case demonstrates that early recognition & intervention can favorably alter the course of this potentially fatal cardiac condition.

Standardized two-step testing of antibody activity in COVID-19 convalescent plasma.

The COVID-19 pandemic revealed an urgent need for rapid profiling of neutralizing antibody responses and development of antibody therapeutics. The current Food and Drug Administration-approved serological tests do not measure antibody-mediated viral neutralization, and there is a need for standardized quantitative neutralization assays. We report a high-throughput two-step profiling approach for identifying neutralizing convalescent plasma. Screening and downselection for serum antibody binding to the receptor-binding domain are followed by quantitative neutralization testing using a chimeric vesicular stomatitis virus expressing spike protein of SARS-CoV-2 in a real-time cell analysis assay. This approach enables a predictive screening process for identifying plasma units that neutralize SARS-CoV-2. To calibrate antibody neutralizing activity in serum from convalescent plasma donors, we introduce a neutralizing antibody standard reagent composed of two human antibodies that neutralize SARS-CoV strains, including SARS-CoV-2 variants of concern. Our results provide a framework for establishing a standardized assessment of antibody-based interventions against COVID-19.

Protocol and statistical analysis plan for the Pragmatic Investigation of optimaL Oxygen Targets (PILOT) clinical trial.

INTRODUCTION: Mechanical ventilation of intensive care unit (ICU) patients universally involves titration of the fraction of inspired oxygen to maintain arterial oxygen saturation (SpO2). However, the optimal SpO2 target remains unknown. METHODS AND ANALYSIS: The Pragmatic Investigation of optimaL Oxygen Targets (PILOT) trial is a prospective, unblinded, pragmatic, cluster-crossover trial being conducted in the emergency department (ED) and medical ICU at Vanderbilt University Medical Center in Nashville, Tennessee, USA. PILOT compares use of a lower SpO2 target (target 90% and goal range: 88%-92%), an intermediate SpO2 target (target 94% and goal range: 92%-96%) and a higher SpO2 target (target 98% and goal range: 96%-100%). The study units are assigned to a single SpO2 target (cluster-level allocation) for each 2-month study block, and the assigned SpO2 target switches every 2 months in a randomly generated sequence (cluster-level crossover). The primary outcome is ventilator-free days (VFDs) to study day 28, defined as the number of days alive and free of invasive mechanical ventilation from the final receipt of invasive mechanical ventilation through 28 days after enrolment. ETHICS AND DISSEMINATION: The trial was approved by the Vanderbilt Institutional Review Board. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences. TRIAL REGISTRATION NUMBER: The trial protocol was registered with ClinicalTrials.gov on 25 May 2018 prior to initiation of patient enrolment (ClinicalTrials.gov identifier: NCT03537937).

Altered pulmonary blood volume distribution as a biomarker for predicting outcomes in COVID-19 disease

Rationale: Evidence suggests that vascular inflammation and thrombosis may be important drivers of poor clinical outcomes in patients with COVID-19. We hypothesized that a significant decrease in the percentage of blood vessels with a cross-sectional area between 1.25-5 mm2 (BV5%) on chest computed tomography (CT) in COVID-19 patients is predictive of adverse clinical outcomes. Methods: Retrospective study of patients seeking acute medical care within a large integrated healthcare network from 3/1/2020-6/30/2020. Patients presenting to the emergency department, undergoing a chest CT within 24 hours of presentation, and COVID-19 testing were eligible for participation. After identification of the COVID-19-positive cohort, a randomly selected group of COVID-19-negative patients were chosen in order to achieve a target study ratio of 60% COVID-19 positive and 40% COVID-19 negative cases for analysis. Results: Patients with COVID-19 had significantly lower BV5% compared to COVID-19 negative patients (25.3% +/- 7.4 vs 30.1 % +/- 9.6;p<0.01). There was no significant difference in BV5% obtained from contrast enhanced CT versus non-contrast CT (p=0.23). Average processing time for BV5% was 9 minutes and 22 seconds (+/- 6 minutes and 3 seconds), with processing time dependent on scan quality. No CT scans were unable to be analyzed. BV5% was predictive of outcomes in COVID-19 patients in a multivariate model, with a BV5% threshold below 25% associated with an odds ratio (OR) 5.58 for death, OR 3.20 for intubation, and OR 2.54 for the composite of death or intubation. A model using age and BV5% had an area under the receiver operating characteristic curve 0.85 to predict the composite of intubation or death in COVID-19 patients. Conclusion: This data suggests BV5% as a biomarker for predicting adverse outcomes in patients with COVID-19 seeking acute medical care.

A hybrid asynchronous-synchronous learning network (HASLN) flipped-classroom approach in engineering education

This paper describes a technique in use at the Faculty of Engineering, UWI (Mona), to offer undergraduate engineering classes by combining collaborative Asynchronous Learning Networks (ALNs) and synchronous group interactions, in a flipped classroom setting. The ALN component involves access to online class materials such as recorded lectures, class notes, assigned and reference books and study guides so that students may watch lectures, write their own notes and consult supplemental materials as needed. A multimedia social network group including the instructors, instructional assistants and all students in the class then provides a forum to pose and answer questions and facilitate collaborative discussions of online material. The ALN class lectures and group interaction are complemented by a Synchronous Learning Network (SLN), using face-to-face meetings where possible and optionally, as necessitated over the past year during the on-going Covid-19 pandemic, using synchronous video conferencing tools. This face-to-face or videoconference enabled SLN component essentially constitutes a 'flipped-class room' approach, where lectures are watched at home and homework and problems are done at school. In person or virtually by interactive videoconference, fully exploiting the collaborative benefits of real-time, teacher-student and studentstudent interactions. The synchronous 'flipped-class room' sessions are used for group discussions, collaborative problem solving as well as supervised student assessment purposes. The flipped classroom sessions serve several important purposes in achieving key goals of effective teaching and learning. First, a moderated content specific question and answer discussion and by a mini-quiz with full access to personally authored lecture motivate and ensure diligence in student assimilation of the online class lectures. This sound foundation then empowers students to use the ALN lecture and supplemental material to successfully complete class assignments and projects in an interactive and collaborative setting. The in-person session also allows the for progressive and rigorous evaluation of learning via periodic tests based on personally completed class-assignments, comprehensive in-term examination(s) with no notes or textbook allowed, and a cumulative closed book, closed notes final examination based on the entire course material covered. The paper also provides general observations on the overall teaching and learning effectiveness and student performance as well as preliminary anecdotal student feedback on the HASLN approach. Finally, we motivate the benefit of implementing the HASLN techniques in High School and pre-college education for Science, Technology, Engineering and Math (STEM) classes. Copyright © 2021 by the International Institute of Informatics and Systemics.

Safety of video-based telemedicine compared to in-person triage in emergency ophthalmology during COVID-19.

BACKGROUND: the need for social distancing midst the COVID-19 pandemic has forced ophthalmologists to innovate with telemedicine. The novel process of triaging emergency ophthalmology patients via videoconsultations should reduce hospital attendances. However, the safety profile of such services were unknown. METHODS: in this retrospective cohort study, we reviewed case notes of 404 adults who used our videoconsultation service from 20/04/2020 to 03/05/2020. We compared these to 451 patient who attended eye casualty in person at the same time who were deemed not to require same day ophthalmic examination. FINDINGS: patients seen by videoconsultations tended to be younger (Median = 43 years, Inter-quartile range = 27 vs Median= 49 years, Inter-quartile range = 28)'. More males used the face-to-face triage (55%) while more females used videoconsultation (54%)%. Fewer patients seen by videoconsultations required specialist review compared to face-face triage [X 2 (1, N = 854) = 128.02, p<0.001)]. 35.5% of the patients initially seen by videoconsultation had unplanned reattendance within 1 month, compared to 15.7% in the group initially seen in person. X 2 (1, N = 234) = 7.31, p = 0.007). The rate of actual harm was no different (at 0% for each method), with perfect inter-grader correlation when graded independently by two senior ophthalmologists. 97% of patients seen on the video platform surveyed were satisfied with their care. INTERPRETATION: we demonstrate comparable patient safety of videoconsultations at one-month follow-up to in person review. The service is acceptable to patients and reduces the risk of COVID-19 transmission. We propose that videoconsultations are effective and desirable as a tool for triage in ophthalmology. FUNDING: the research supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology who fund PT and DS's time to conduct research. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

Passive Immunity Trial for Our Nation (PassITON): study protocol for a randomized placebo-control clinical trial evaluating COVID-19 convalescent plasma in hospitalized adults.

BACKGROUND: Convalescent plasma is being used widely as a treatment for coronavirus disease 2019 (COVID-19). However, the clinical efficacy of COVID-19 convalescent plasma is unclear. METHODS: The Passive Immunity Trial for Our Nation (PassITON) is a multicenter, placebo-controlled, blinded, randomized clinical trial being conducted in the USA to provide high-quality evidence on the efficacy of COVID-19 convalescent plasma as a treatment for adults hospitalized with symptomatic disease. Adults hospitalized with COVID-19 with respiratory symptoms for less than 14 days are eligible. Enrolled patients are randomized in a 1:1 ratio to 1 unit (200-399 mL) of COVID-19 convalescent plasma that has demonstrated neutralizing function using a SARS-CoV-2 chimeric virus neutralization assay. Study treatments are administered in a blinded fashion and patients are followed for 28 days. The primary outcome is clinical status 14 days after study treatment as measured on a 7-category ordinal scale assessing mortality, respiratory support, and return to normal activities of daily living. Key secondary outcomes include mortality and oxygen-free days. The trial is projected to enroll 1000 patients and is designed to detect an odds ratio ≤ 0.73 for the primary outcome. DISCUSSION: This trial will provide the most robust data available to date on the efficacy of COVID-19 convalescent plasma for the treatment of adults hospitalized with acute moderate to severe COVID-19. These data will be useful to guide the treatment of COVID-19 patients in the current pandemic and for informing decisions about whether developing a standardized infrastructure for collecting and disseminating convalescent plasma to prepare for future viral pandemics is indicated. TRIAL REGISTRATION: ClinicalTrials.gov NCT04362176 . Registered on 24 April 2020.