Robust, efficient workflow to establish, culture, and functionally assess primary-isolated airway epithelial cells

Background: Air-liquid interface (ALI) and organoid culture are key techniques for differentiating human airway epithelial cells (HAECs). The efficiency and robustness of these assays often depends on the quality of primary-isolated cells, but primary cell isolation workflows, with which the user controls the choice of isolation method, cell culture medium, and culture format, may reduce reproducibility. Therefore, an optimized, standardized workflow can enhance and support isolation of epithelial cells from diseased donors with potentially rare cystic fibrosis (CF) mutations or particularly sensitive cell populations. We have developed a standardized workflow for isolation and culture of freshly derived airway epithelial cells. Method(s): Briefly, HAECs isolated from primary tissue were expanded in PneumaCult-Ex Plus Medium for 1 week and then seeded into Corning Transwell inserts and expanded until confluency. The cells were then differentiated in PneumaCult-ALI Medium for at least 4 weeks. To assess differentiation efficiency in ALI culture, the cells were immunostained to detect Muc5AC, acetylated tubulin, and ZO-1 to identify goblet cells, ciliated cells, and apical tight junctions, respectively, aswell as SARS-CoV-2 cell entry targets angiotensin-converting enzyme 2 and transmembrane serine protease 2. Ion transport and barrier function of the ALI culturesand response to CF transmembrane conductance regulator (CFTR) correctors were also measured. In addition, freshly derived HAECs were seeded into Corning Matrigel domes in the presence of PneumaCult Airway Organoid Seeding Medium. Oneweek later, the mediumwas changed to PneumaCult Airway Organoid Differentiation Medium and maintained for an additional 3 weeks to promote cell differentiation. These airway organoids were then treated with CFTR corrector VX-809 for 24 hours, followed by 6-hour treatment with amiloride, forskolin, and genistein to induce organoid swelling. Result(s): Our results demonstrate that ALI cultures derived from CF donors displayed partial rescue of CFTR across multiple passages after treatment with VX-809. Airway organoids were found to express functional CFTR, as evidenced by forskolin treatment, which induced a 64 +/- 14% (n = 1 donor) greater organoid area than in vehicle control-treated airway organoids. Airway organoids derived from CF donors displayed a loss of forskolininduced swelling, which could be partially re-established with VX-809 treatment (29 +/- 9%, n = 3). Conclusion(s): In summary, the PneumaCult workflow supports robust, efficient culture of primary-airway epithelial cells that can be used as physiologically relevant models suitable for CF research, CFTR corrector screening, and studying airway biology.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

Differentiating infectious from non-infectious respiratory disease in the cat and dog

This paper describes the clinical signs and use of differential laboratory diagnostic techniques (computed tomography, cytology, histopathology, antigen/antibody detection and polymerase chain reaction) for infectious (viral, bacterial, fungal and parasitic) and non-infectious (inflammatory/immune mediated, neoplastic, cardiac, malformation, foreign body, smoke inhalation, aspiration of caustic material, non-cardiogenic, pulmonary oedema, traumativ, pneumothorax, pulmonary contusions and idiopathic) causes of respiratory diseases in cats and dogs in Ontario, Canada.

Determining the best practices for remote experiential rotations

Introduction: During the COVID-19 pandemic, clinical sites have closed their doors to student placements, leading to the implementation of remote rotations. The purpose was to determine best practices for distance preceptorship from the student's perspective. Method(s): A survey was sent to the pharmacy students at the Leslie Dan Faculty of Pharmacy who have completed at least one remote rotation. Result(s): Forty-eight out of 121 students (39%) completed the survey. It was found that 83% of the students were motivated during the start of their rotations, while 48% remained motivated throughout. Students who remained motivated had clear expectations set from the beginning, felt comfortable communicating issues regarding their assigned work with their preceptor, had similar rapport with remote preceptors as with in-person preceptors, had a preceptor who is always available for questions, and had a work environment free of distractions. Discussion(s):There are numerous best practices students and preceptors can utilise during a remote rotation to help students remain motivated. Preceptors and students should work together so that students remain motivated throughout their rotation. Setting expectations, having good communication, getting to know their preceptor, and having a work environment free of distractions are key factors for conducting a remote rotation. Copyright © 2020 FIP.

Territories, politics and governance of the Covid-19 pandemic

As a major public health and socio-ecological crisis, the Covid-19 pandemic has raised significant challenges, arguably affecting the everyday life of most individuals on the planet. The pandemic has transformed social relationships within families, communities and nations, awakening a spirit of care and reciprocity as well as engendering new mechanisms of control and surveillance to confront the dialectic of life and death. This editorial introduces the special issue composed of nine articles that engage with themes related to the responses to the pandemic and reflects on the implications of Covid-19 for scholarly questions on the politics and governance of territorial processes.

Creating Efficiency in Blood Center Therapeutic Apheresis Services in Response to Pandemic Era Challenges

Background/Case Studies: Ongoing labor shortages occurring during the SARS-Co-V-2 pandemic caused the blood center to re-evaluate current nurse staffing schedules and clinical offerings in the therapeutic apheresis department in order to maintain high quality apheresis delivery to hospitals and improve work-life balance for the apheresis nursing team. A major area of concern was the amount of on-call coverage the apheresis nursing staff experienced. Study Design/Methods: An internal working group (WG) of medical, nursing, administrative, and financial subject matter experts was assembled to evaluate the current model of 24-h, 7-day-week apheresis coverage with nurses regularly scheduled to cover day shift hours and take on-call for after hours and weekends. The WG reviewed hospital apheresis contracts, nurse on-call schedules, types of apheresis procedures, number of after-hours procedures, and geography of service requests for the prior 12 months. Alternative models for nursing staffing that would reduce on-call for the nurses were considered, including full nursing coverage for 3 out of 3 shifts, flexible 3- and 4-day work weeks, and limiting apheresis services to business hours only. Results/Findings: It was determined that covering 3 out of 3 shifts with full nursing staff in order to eliminate oncall would require hiring 8 additional nurses (representing a 25% increase in staff) at a cost of $650K annually. Flexible shifts of 3- and 4-day work weeks added scheduling complexity without resolving the on-call issue sufficiently. Analysis of the types of procedures performed after hours revealed that over 70% were non-emergencies. Limiting hours of apheresis services to 8A-5P M-F with after-hours available only for emergencies approved by the ordering clinician and blood center medical director offered a costneutral approach that mitigated on-call for the nurses and relieved current nursing staffing shortages. Conclusion(s): Chronic and significant labor shortages emerging from the pandemic necessitated changes to the way blood center apheresis services were offered to our hospitals. In-depth analysis of current offerings and types of procedures performed after business hours resulted in the development of an alternative, cost-neutral model for maintaining apheresis service levels and improving work-life balance for the apheresis nursing staff.

Ipax-1: Phase 1/2 Study of 131i-Iodophenylalanine (131iipa) Combined with External Radiation Therapy as Treatment for Patients with Relapsed Glioblastoma

BACKGROUND: A novel therapeutic approach using molecularly targeted radiation is currently in development for patients with recurrent GBM. Many tumor types, including GBM, overexpress the L-type amino transporter 1 (LAT-1)4, which is able to internalize the small-molecule amino acid derivative, 4-L-[131I] iodo-phenylalanine (131I-IPA). In preclinical research, combining 131I-IPA with external radiation therapy (XRT) yielded addi- tive cytotoxic effects. Tumoral accumulation of 131I-IPA was confirmed in a proof-of-principle study using single doses of 2-7 GBq 131I-IPA as a monotherapy or in combination with XRT in patients with recurrent GBM. The objective of the IPAX-1 study was to evaluate the safety, tolerability, dosing schedule, and preliminary efficacy of 131I-IPA in combination with secondline radiotherapy in patients with recurrent GBM. METHOD(S): IPAX-1 is a multi-center, open-label, single-arm, dose-finding phase 1/2 study. Key inclusion criteria: 1. Confirmed histological diagnosis of GBM with evidence of first recurrence 2. History of GBM standard therapy 3. >= 6 months since end of first-line XRT 4. Pathologically increased amino acid tumor uptake shown by molecular imaging 5. Current indication for repeat radiation 6. Gross tumour volume of up to 4.8 cm diameter. Treatment: In phase 1 of the study patients received intravenous 131I-IPA at a dose level of 2 GBq administered in one of three different dosing regimens: single dose group with 2 GBq before radiation, 3 (f)-fractionated-parallel group: 3 x 0.67 GBq during XRT and 3 (f)-fractionated-sequential group: 0.67 GBq x 1 -> XRT -> 0.67 GBq x 2. XRT is delivered in 18 fractions of 2 Gy each. RESULT(S): 10 patients were randomized;one patient with Covid related death was withdrawn from analysis. Survival from start of TLX101 therapy showed mPFS2 of 4.33 M (95% -CI 4.18 - 4.48), PFS-6: 18 % and mOS2 of 15.97 M (95% -CI 2.9 - 29.1) at data lock 09/2021. Updated results will be presented at the meeting. CONCLUSION(S): There were no clinically relevant laboratory changes over time. Urinalysis, vital signs, and ECG did not show any clinically relevant changes from baseline. There were no notable differences in safety and tolerability between groups. Injections of single or fractionated doses of 131I-IPA containing a total activity of 2 GBq in combination with XRT in patients with recurrent GBM were safe and well tolerated. Survival data look promising;extension cohort will be treated in a phase II study in Linz;phase 1/2 study in first line setting is planned.

Treatment-Resistant Pemphigoid Following SARS-Cov-2 Vaccination

As the SARS-CoV-2 vaccinated population increases, there have been many reports of vaccine-induced cutaneous reactions but scarce information on vaccine-induced autoimmune bullous disease. Vaccinations have been associated with the unmasking or development of autoimmune bullous disease;however, there is little data on SARS-CoV-2, specifically. We report a rare case of new-onset pemphigoid in a 70-year-old male following the second dose of the mRNA-1273 vaccine. The patient’s disease has been refractory to treatment, thus the underlying pathophysiology in vaccine-induced pemphigoid is likely unique, and further investigation into this pathophysiology is warranted. © 2022 THE AUTHORS.

The COVID-19 pandemic's impact on out-of-hospital cardiac arrest incidence and survival outcomes: a systematic review

Background: The COVID-19 pandemic has overwhelmed healthcare systems, strained ambulance services and, directly or indirectly, affected community responses to patients who experience cardiac arrests outside hospitals. Previous observational studies have shown a notable rise in Out-of-Hospital Cardiac Arrest (OHCA) cases during the pandemic in different parts of the world compared to the same period in 2019, including the United Kingdom and the United States 1, 2. This systematic review’s intention is to shed light on the incidence and survival outcomes of adult OHCA patients. Methods: A comprehensive review of MEDLINE, EMBASE, the Cochrane Library, Web of Science, WHO’s Global Index Medicus, WHO’s Global Research Literature on Coronavirus 2019 and medRxiv up to 8 September 2021 was conducted to identify articles and preprints that reported OHCA figures before and during the COVID-19 pandemic. Primary outcomes were OHCA incidence, Return of Spontaneous Circulation (ROSC) and survival to hospital discharge. Results: Twenty-one studieswere included in the final analysis, out of 2877 potentially eligible records. There were 12,619 OHCA cases during the COVID-19 pandemic, compared with 8353 OHCA cases in the same period of 2019, representing a 51.1% increase in OHCA incidence during the pandemic. In terms of survival outcomes, ROSC and survival to hospital discharge rates were substantially reduced during the pandemic compared to the pre-pandemic period. Conclusion: The pandemic has had an impact on the incidence and survival outcomes among adult OHCA patients compared to the prepandemic period. Moreover, the pandemic has delayed ambulance care processes and disrupted community responses to OHCA. 1. Fothergill RT et al. Out-of-hospital cardiac arrest in London during the COVID-19 pandemic. Resusc Plus. 2021;5:100066. 2. Lai PH et al. Characteristics associated with out-of-hospital cardiac arrests and resuscitations during the Novel Coronavirus Disease 2019 pandemic in New York City. JAMA Cardiol. 2020;5(10):1154– 63.(Table Presented)(Table Presented)

Natural history of coagulopathy in patients with cancer infected with COVID19: A real-world data (RWD) analysis

Background and Objective: Studies of hospitalized patients (pts) with COVID19 indicate that arterial or venous thrombotic complications occur in up to half of pts. Risk of these severe complications in pts with cancer is unknown. We estimated the incidence of arterial thrombosis (AT) and venous thromboembolism (VT) using RWD from pts with active or history of cancer with COVID19. Methods: Adult pts with cancer receiving treatment in community health systems, with COVID19 identified via ICD code or lab confirmation in 2020, were reviewed for incident AT and VT in a 90 day window following COVID19 diagnosis (index). AT was acute myocardial infarction (MI) or acute ischemic or embolic stroke (S). VT was acute deep venous thrombosis (DVT) or acute pulmonary embolism (PE). Medication use (anticoagulant, antiplatelet, statin) and comorbidities were assessed 6 months and 1 year prior to index, respectively. Results: Median age of 7,591 pts with cancer and COVID19 was 67 years and median follow up was 90 days. 32% of pts were hospitalized within 14 days, 2% received ventilator support, 6% had cardiovascular disease (CVD) and 1% had prior VT. Absolute risk of VT was significantly higher than AT (3% vs. 2%, chi square p= < 0.001), with 161 pts experiencing AT [81 (1%) MI;80 (1%) S] and 240 pts experiencing VT [99 (1%) DVT;158 (2%) PE]. This trend held across most subgroups (Table 1). The incidence rate per person-year was 0.094 for AT (0.047 MI, 0.046 S) and 0.141 for VT (0.058 DVT, 0.092 PE). CoxPH models did not show age, sex, comorbidities or medication use as significantly associated with higher probability of AT or VT. Conclusions: RWD showed pts with cancer and COVID19 were at higher risk for VT than AT. Pts who received ventilator support, or had prior VT or prior CVD had highest risk for these events. Severity of these outcomes emphasizes the need for risk reducing interventions. (Table Presented).

The association between school-aged children's self-reported levels of playfulness and quality of life: a pilot investigation

Playfulness and quality of life (QoL) appear to be related constructs;however, no studies have explored the potential association between them to date. Playfulness and QoL are important practice-related concepts for education and therapy professionals who work with children and their families. This study examined the potential links between children's self-reported playfulness and QoL. Thirty-one typically developing children aged 8-12 years (average age 10 years and 9 months, standard deviation = 1.12;61.29% female) completed the Children's Perceptions of Their Play and the KIDSCREEN-52 instruments. It is noted that the onset of the COVID-19 pandemic during 2020 made participant recruitment and the execution of the study challenging. Data were analyzed using Spearman rho correlations and linear regression with bootstrapping. Data analysis results revealed statistically significant associations and predictive relationships between QoL-related physical wellbeing to active play and free time;QoL-related psychological wellbeing to the child's overall playfulness;the child's reported levels of QoL-related autonomy and their free time;and the child's QoL-related school environment to planned activities (p < .05 & p < .01). The study findings provide preliminary evidence that significant correlation and predictive relationships exist between aspects of children's self-reported playfulness and quality of life.

Biomarker Levels Concur with a Risk Stratification Criteria in Covid-19 Pneumonia, a Role for a Prognostic-Tool for Identification of Clinical Deteriorators

Rationale: COVID-19 patients present with a number of clinical symptoms ranging from mild, moderate to severe, while only a subgroup of patients, who requires high-dependency critical care resources, accounts for most of the COVID-19 associated health care expenditure and death. A reliable prognostic tool is therefore required to identify patients at risk of developing severe COVID-19 pneumonia. To address this unmet need, we tested a wide range of potentially important peripheral blood biomarkers in a group of clinically risk-stratified COVID-19 patients in order to identify most relevant candidate biomarker(s) predictive of disease progression. Methods: Patients and healthy controls recruited to this study are summarised in Figure 1. Biomarkers levels were analysed using ANOVA across the severity groups. Spearman-correlation coefficients against pairs of average levels from each biomarker within severity-group and healthy controls were assembled into a 76x76 matrix and agglomerative hierarchical clustering was applied to generate the final heatmaps. Linear-discriminant analysis (LDA) was carried out on a reduced optimised set of biomarkers to explore the boundaries between the clinical severity groups.Results: Degree of lymphopaenia, neutrophil levels, TNF-α, INR-levels, and pro-inflammatory cytokines;IL6, IL8, CXCL9 and D-dimers were significantly increased in COVD-19 patients compared to healthy controls (p<0.05, 95% C.I.). C3a and C5 was significantly elevated in all categories of severity compared to healthy controls (p<0.05), C5a levels were significantly different between “moderate” and “severe” categories (p<0.01). sC5b-9 was significantly elevated in the “moderate” and “severe” category of patients compared to healthy controls (p<0.001).Heatmap analysis demonstrated distinct visual differences of biomarker profiles between the clinical severity groups. LDA on the deteriorators, non-deteriorators and healthy volunteers as a combined function of the predictor variables: C3, eosinophil-counts, granulocyte colony-stimulating factor (G-CSF), fractalkine, IL10, IL27, LTB4, lymphocyte count, MIG/CXCL9, M-CSF, platelet count and sC5b-9 showed clear separation between the groups based on biomarker/blood-count levels.Conclusions: Diagnostic and clinical assessments followed by robust statistical and machine learning approaches could identify peripheral blood biomarkers for prognostic stratification of patients in COVID-19. Our results would be helpful for clinicians and supports the use of point of care devices that can quantify multiple analytes. (Lui G, et al., Pointof- care detection of cytokines in cytokine storm management and beyond: Significance and challenges. VIEW. 2021;2: 1-20.). Such would allow for more efficient management and resource allocation. 1 (Figure Presented).

Highly Expandable Human Alveolar Organoids to Study Respiratory Diseases

Organoids are emerging to be an excellent tool for studying human development and disease. The COVID-19 pandemic has highlighted the importance of physiologically relevant alveolar infection models that include both alveolar epithelial type 1 (AT1) and type 2 (AT2) cells. To address the need for an alveolar organoid culture system for respiratory research, we developed the PneumaCult™ Alveolar Organoid Expansion and Differentiation Media for the highly efficient expansion of isolated primary human AT2 cells and subsequent differentiation into AT1 cells. Alveolar organoids were established from a panel of various donors (n=5) by culturing purified human AT2 cells in Corning® Matrigel® domes with serum-free PneumaCult™ Alveolar Organoid Expansion Medium. Typically by day 10-14 the organoids are fully established and display a spherical morphology. Alveolar organoids can then be either expanded long-term by passaging cultures as single cells in Expansion Medium or differentiated into AT1 cells using the PneumaCult™ Alveolar Organoid Differentiation Medium. Organoids in PneumaCult™ Alveolar Organoid Expansion Medium contain self-renewing AT2 cells marked by the expression of HT2-280 in 89.9 +/- 14.5 (mean +/- SD;n=5 donors) of cells and the presence of Pro-SPC, demonstrate a great expansion potential of > 10,000-fold with more than 13 population doublings within 10 passages (n=5 donors). Alveolar organoids differentiated for 10 days in the PneumaCult™ Alveolar Organoid Differentiation Medium downregulate AT2 markers HT2-280 and Pro-SPC and start expressing AT1 markers HT1-56 in 93.8 +/- 7.2 (mean +/- SD;n=5 donors) of cells and are positive for RAGE and GPRC5a. Furthermore, we assessed the expression of SARS-CoV-2 entry receptor ACE2, which is present in both undifferentiated and differentiated alveolar organoids.To investigate the use of these alveolar organoids for infectious disease modeling, AT2-containing alveolar organoids were transduced with a GFP-labelled Respiratory Syncytial Virus (RSV). Alveolar organoids were susceptible to viral infection and replication was confirmed by fluorescence microscopy and quantitative PCR. In summary, the PneumaCult™ Alveolar Organoid Expansion and Differentiation Media are highly efficient and reproducible tools for the feeder-free expansion of AT2 cells and robust differentiation into AT1 cells, which can be used for infectious disease modeling.

Molecular Changes in Circulating Cell Free DNA from BRCA1 and BRCA2 Mutation Carriers with Tubal Precursor Lesions and Occult Early High-GradeSerous Ovarian Cancer at Risk-Reducing Surgery

High grade serous ovarian cancer typically presents at advanced stage with a median survival of 44 months. Small precursors to this cancer are found in the fallopian tube and likely seed the ovary and peritoneum simultaneously. Early detection is urgently needed and ideally would detect precursor lesions. This award will determine if DNA methylation patterns exhibited in circulating cell-free DNA could be used to detect precursor lesions. During the first year of the award, application for province-wide (Ontario) research ethics approval was submitted to umbrella all 4 participating hospitals. This umbrella approval was obtained;however, we are awaiting final approval from 2 hospitals, which was delayed by the covid-19 shutdown. All research activities were halted (Covid-19 research being the exception) and department staff were redeployed to other hospital activities, causing a back-up of research-related activity. All centres are currently reopening (in stage 2) and study approval should be forthcoming. The Material Transfer Agreements have been started by Sinai Health System and once final REB/IRB approval has been obtained, these will be finalized across the all institutions. Patient samples for use in this study as identified have been secured and we are poised to complete the study once approvals are finalized.

It's Challenging but Doable: Lessons Learned from a Remote Collaborative Coding Camp for Elementary Students

The COVID-19 pandemic shifted many U.S. schools from in-person to remote instruction. While collaborative CS activities had become increasingly common in classrooms prior to the pandemic, the sudden shift to remote learning presented challenges for both teachers and students in implementing and supporting collaborative learning. Though some research on remote collaborative CS learning has been conducted with adult learners, less has been done with younger learners such as elementary school students. This experience report describes lessons learned from a remote after-school camp with 24 elementary school students who participated in a series of individual and paired learning activities over three weeks. We describe the design of the learning activities, participant recruitment, group formation, and data collection process. We also provide practical implications for implementation such as how to guide facilitators, pair students, and calibrate task difficulty to foster collaboration. This experience report contributes to the understanding of remote CS learning practices, particularly for elementary school students, and we hope it will provoke methodological advancement in this important area. © 2022 ACM.

Teaching Software Quality Assurance (SQA) during COVID-19 Using the HyFlex Approach - Course Design, Results, and Experiences

This full paper discusses the HyFlex pedagogical approach to teaching a highly interactive face-to-face Software Quality Assurance (SQA) course during the COVID-19 pandemic. HyFlex, short for hybrid-flexibility, is a teaching model where instructors and students have the option to attend scheduled courses face-to-face (F2F) or remotely. In this teaching model the learning outcomes for the course remain the same for all who enroll regardless of the mode of attendance. Our HyFlex SQA approach consists of lectures (in class, with video recordings), face-to-face activities, as well as group assignments, group projects, and exams all facilitated through an online campus management system. During the lecture period, the instructor delivers content in the form of lecture slides and writing on a whiteboard. This poses significant challenges for the instructor, as the learning outcomes have to be delivered in different modalities, but with the same quality. This is particularly difficult in SQA courses, as these require instruction in formal methods as well as systematic justification of engineering choices, both of which are best facilitated in F2F fashion that implement Think-Pair-Share (TPS) amongst students. TPS is an active learning technique in which students are allocated adequate time to think individually on a task posed by the instructor, followed by pair discussions, and then as a class discussion. The task given by the instructor is of similar complexity to that which is covered as an example during lecture. Online synchronous activities involve students participating in TPS by working collaboratively as a group on tasks that correspond with concepts covered in the slide-based lectures. This way students learn from each other by thinking individually then sharing ideas in the classroom, thus contributing to better understanding of course content. For assignments and projects students are allocated a portion of the class time to meet with group members and discuss their activities. Groups also have the option to ask the instructor questions aloud that will help other groups to complete their assignments and projects successfully. Delivering these in a hybrid format was required during the fall of 2020 due to COVID-19 restrictions. The results show that while performance in projects and homework assignments remained constant, final exam performance was significantly (p < 0.05) lower in 2020 compared to previous course offerings. We also noted a lower enrollment, higher participatory effort on both instructors and students, and a subjectively decreased feeling of collaboration. Nevertheless, students rated their perceived learning experience as high and regard HyFlex learning facilities as adequate. In this paper we adopted a HyFlex teaching model that incorporates reduced F2F seating, educational tools such as Blackboard, Panopto, Zoom, Google docs, and Discord. We conclude by discussing some challenges experienced with HyFlex teaching model and recommendations for adopting the teaching model by other instructors who teach CS courses that involve a considerable amount of group activities. © American Society for Engineering Education, 2021

Telemedicine Has Acceptable Usability and High Satisfaction in Patients with Sickle Cell Disease

Introduction: The COVID-19 pandemic presented exceptional challenges to caring for adults with sickle cell disease (SCD) and necessitated a rapid transition to telemedicine, disrupting established care systems within a population that already faces unique and challenging medical needs. Although implementation of telemedicine care assumed reliable patient access to the requisite technology, as well as adequate spaces in which to complete visits, pre-pandemic barriers to in-person visits were also considerable, and many patients lacked access to reliable transportation and childcare or could not afford to miss work to attend clinic. Given the scarcity of research on the acceptability of telemedicine care for SCD patients, the pandemic has provided a critical and necessary opportunity to study patient satisfaction when using telemedicine modalities for regular SCD care. The objective of this study was to identify which patient groups rate telemedicine high in satisfaction and usability. Methods: We surveyed 99 patients of the Sickle Cell Clinic for adults at Johns Hopkins who had any form of SCD, were age 18 or above, and participated in at least one video visit between March-July 2020. Telemedicine satisfaction was assessed by the Telemedicine Satisfaction Questionnaire (TSQ), and usability was assessed by the System Usability Scale (SUS). Patients' engagement in their healthcare was assessed by the Patient Activation Measure (PAM13). We conducted linear regression with TSQ and SUS as outcomes and participant characteristics as predictors. Results: Participant characteristics (briefly, mean age 39, 95% African American, 72% female, and 81% with education level above high school) and their association with TSQ and SUS are shown in Table 1. Mean SUS was 72/100 (SD 15), slightly above the defined average usability of 68;mean TSQ was 4.1 (SD 0.5) on a 5-point Likert scale. Participants tended to prefer video visits for their regular care (mean rating of 6.6/10, SD 2.9) but not for management of acute pain (mean rating of 4.9/10, SD 3.2). Participants who preferred video visits for regular SCD care reported higher SUS (p<0.01) and TSQ (p<0.001). We examined the effects of age, sex, income, and education level on TSQ and SUS;higher SUS was associated with an education level above high school (p<0.05), but no other associations were consistently significant. Higher SUS was also associated with having private insurance compared to public insurance (p<0.01) and being employed full-time compared to being unemployed (p<0.05). Disability status was negatively associated with SUS (p<0.05) but not TSQ. PAM13 was associated with higher telemedicine approval as measured by both TSQ and SUS (p<0.01). Conclusions: Our findings suggest that telemedicine has above-average usability and high satisfaction for SCD patients, regardless of age, sex, and income. Patients who were more engaged with their healthcare were more likely to rate telemedicine satisfaction and usability high. Because SUS was negatively associated with disability, lower education level, public insurance, and unemployment, patients within these groups may need more assistance with telemedicine. To improve usability, clinics may consider incorporating support services for patients who have difficulty using telemedicine platforms. Altogether, telemedicine demonstrates promising acceptability to SCD patients across multiple demographic groups and may serve as another method in the toolkit for increasing accessibility to high quality care for these patients. [Formula presented] Disclosures: Lanzkron: Pfizer: Current holder of individual stocks in a privately-held company;Bluebird Bio: Consultancy;Novo Nordisk: Consultancy;GBT: Research Funding;Teva: Current holder of individual stocks in a privately-held company;Shire: Research Funding;CSL Behring: Research Funding;Novartis: Research Funding;Imara: Research Funding.

A pathway transformation to transition from a ‘routine’ to a ‘responsive’ severe asthma service in the post COVID era

P154 Figure 1A pathway transformation to transition from a ‘routine’ to a ‘responsive’ severe asthma service in the post COVID era[Figure omitted. See PDF]ConclusionsThe COVID-19 pandemic has necessitated a comprehensive re-evaluation of services and care pathways across the NHS. Transitioning from a ‘routine’ to ‘responsive’ patient-triggered service has facilitated flexible but personalised care empowering patients in the self-management of their asthma and significantly reducing the burden of ‘routine’ follow-up for patients and the MDT. This has reduced waiting times and increased capacity for new patient assessments whilst ensuring patients are offered timely reviews when their asthma control deteriorates, delivering equitable access across the system with the potential to improve patient outcomes.

Measures of inflammation, complement activation and coagulation in patients with COVID-19

S56 Table 1Table to show measures of complement activation, inflammation and coagulation in patients with COVID-19 stratified by disease severityMildModerateSevereOverall P-ValueMild vs Mod*Mild vs Sev*Mod vs Sev*Number (%)30289----CRP (mg/L)75.5 [28.5,117.25]93.5 [72,143.5]60 [34,157.5]NSNSNSNSFerritin (ug/L)426 [290.5,847.5]728 [381.25,1071.5]857 [443,1607.5]NSNSNSNSPCT (ug/L)0.08 [0.06,0.19]0.16 [0.09,0.49]0.19 [0.12,0.8]0.019NS0.046NSLDH (U/L)708.5 [523.5,903]830 [569,1122]1037 [927.5,1086]0.008NS0.006NSPlatelets (10*9/L)220 [174.75,328.75]255 [203.5, 335]292 [209.5, 329.5]NSNSNSNSINR1.1 [1.08,1.23]1.1 [1.1, 1.2]1.1 [1.1, 1.15]NSNSNSNSAPTR0.9 [0.9,1.0]0.9 [0.9, 1.0]1.0 [0.95, 1.10]NSNSNS0.038D-dimer (ugFEU/ml)0.56 [0.38,0.95]0.74 [0.55, 1.52]0.85 [0.54, 19.2]NSNSNSNSFibrinogen (g/L)4.45 [4.05,5.22]4.7 [4.3, 6.38]4.3 [3.9, 6.0]NSNSNSNSThrombin-AT III Complex ug/L)4.75 [2.65,12.13]8.8 [5.3, 12]14.3 [6.9, 40.7]0.045NSNSNSProthrombin Fragment 1&2 (pMol/L)275 [164.5,380.5]311 [163, 492]301 [258, 709]NSNSNSNSCH50 (U Eq/ml)123.4 [101.75,174.7]113.4[88.68, 153.43]114.7 [74.6,158.9]NSNSNSNSComplement C5a (ng/ml)29 [21.5, 36]36.5[25.5, 48.75]68 [39.5,122.5]<0.0010.0380.001NSComplement C5 (mg/L)270 [235.25,290.5]263[235.25, 279]276 [220,299.5]NSNSNSNSComplement C3 (g/L)1.5 [1.25,1.77]1.48[1.33, 1.71]1.56 [1.16,1.73]NSNSNSNSSC5b-9 complex (ng/ml)1070.46 [836.41,1632.17]1725.48[1092.62, 2403.3]2392.66 [1245.68,5145.88]0.006NS0.019NSComplement Fragment Bb (µg/ml)0.2[0.15,0.27]0.25[0.17, 0.3]0.29 [0.2,0.43]NSNSNSNSComplement C3a ng/ml)296.88[244.33,345.22]325.88[248.33, 484.03]460.23 [282.49,652.1]NSNSNSNS*P-values given a Bonferroni adjustment to allow for multiple testing between subgroupsDiscussionOur findings demonstrated increased levels of complement activity in patients with COVID-19, particularly in those patients requiring non-invasive and mechanical ventilation and those patients that deteriorate requiring increasing ventilatory support. The complement cascade is a key player in protective immunity against pathogens, with its activation orchestrating key immunoprotective and anti-inflammatory effects Increased activation of the complement cascade may contribute to the dysregulated and destructive inflammatory response that leads to multi-organ failure and our findings suggest a potentially important treatment target for COVID-19.