Immune System Development Processes with Special Emphasis on Relationship to Potential Mechanisms of MIS-C

Development of the mammalian immune system requires the intersection of myriad internal and external signals, from the migration of pluripotent stem cells to interactions with the vaginal microbiome during partuition to environmental factors that shape immune processes throughout life. Because the sequence of immune developmental events is fairly transcripted across time, multiple windows of susceptibility exist that can lead to immune dysfunction when these developmental events are perturbed. Additionally, early-life immune dysfunction can persist, leading to increased disease risk across the lifespan. Immune dysfunction can present functionally as suppression, hyperresponsivity, or inappropriate inflammation and molecularly, may involve multiple cells and signaling pathways. Thus, scenarios that lead to multisystem inflammatory syndrome in children (MIS-C) can be complex and multifaceted. This presentation will consider windows of susceptibility as well as external factors that may increase the risk of MIS-C.

Mid-density Gene Expression profiling of SARSCOV-2 infected samples using Applied BiosystemsTM TaqManTM Flexible Array Panels

Background/Objectives: The broad spectrum of clinical manifestations from SARS-COV-2 infection and observed risk factors for severe disease highlight the importance of understanding molecular mechanisms underlying SARS-CoV-2 associated disease pathogenesis. Research studies have identified a large number of host proteins that play roles in viral entry, innate immune response, or immune signalling during infection. The ability to interrogate subsets of these genes simultaneously within SARSCOV-2 infected samples is critical to understanding how their expression contribute to phenotypic variability of the disease caused by the pathogen. Method(s): 30 Nasopharyngeal swab were obtained and included SARS-CoV-2 infected and control samples. RNA was extracted, reverse transcribed and loaded onto flexible TaqMan array panels designed specifically for targeting the most cited genes related to SARS-COV-2 entry and restriction factors as well as cytokines, chemokines, and growth factors involved in the pathogenesis. Result(s): Our data indicated that not only were the levels of several of these host factors differentially modulated between the two study groups, but also that SARS-CoV-2 infected subjects presented with greater frequency of several important inflammatory cytokines and chemokines such as CCL2, CCL3, IFNG, entry receptors such as ACE2, TMRPS11A, and host restriction factors including LY6E and ZBP1. Conclusion(s): TaqMan array plates provide a fast, midthroughput solution to determine the levels of several virus and host-associated factors in various cell types and add to our understanding of how the pathogenesis may vary depending on gender, age, infection site etc.

Optimizing mRNA vaccines and virusmediated CAR T-cell therapy for immuno-oncology: Synthetic tools for gene modification

With the success of mRNA vaccines during the COVID-19 pandemic and CAR T-cell therapies in clinical trials, there is growing opportunity for immunotherapies in the treatment of many types of cancers. Lentiviral vectors have proven effective at delivery of genetic material or gene editing technology for ex vivo processing, but the benefits and promise of Adeno-associated virus (AAV) and mRNA tools for in vivo immunotherapy have garnered recent interest. Here we describe complete synthetic solutions for immuno-oncology research programs using either mRNA-vaccines or virus-mediated cell and gene engineering. These solutions optimize workflows to minimize screening time while maximizing successful research results through: (1) Efficiency in lentiviral packaging with versatility in titer options for high-quality particles. (2) A highthroughput viral packaging process to enable rapid downstream screening. (3) Proprietary plasmid synthesis and preparation techniques to maintain ITR integrity through AAV packaging and improve gene delivery. (4) Rapid synthesis, in vitro transcription, and novel sequencing of mRNA constructs for complete characterization of critical components such as the polyA tail. The reported research demonstrates a streamlined approach that improves data quality through innovative synthesis and sequencing methodologies as compared to current standard practices.

Patients Characteristics, Vaccine Uptake, Healthcare Resource Utilization and Costs Associated with Acute COVID-19 during the Omicron Predominant Period in Brazil: A Nationwide Database Study

Objectives: The coronavirus disease 2019 (COVID-19) pandemic has imposed significant burden on Brazil's health system. The present study aims to describe patients' demographic and clinical characteristics, vaccine uptake and assess healthcare resource utilization (HCRU) and costs associated with acute COVID-19 in Brazil during the Omicron predominant period. Method(s): A population-based retrospective study was conducted using the National Health Data Network (RNDS), National Vaccination Campaign against COVID-19 data and surveillance data in public setting. Individuals with positive COVID-19 test results between January-April 2022 were identified. Patients' demographics, comorbidities, vaccination status, HCRU for those who were admitted to hospitals and their associated costs were described by age groups. Result(s): A total of 8,160,715 COVID-19 cases were identified and 2.7% were aged <5 years, 11.6% were 5-19 years, 76.9% were 20-64 years and 8.7% were >= 65 years. The presence of comorbidity was 23.1% with a higher prevalence of comorbidities in the elderly (61.8% for 65-74 years and 71.2% for >=75 years). Regarding COVID -19 vaccination uptake, among those aged <=19 years, 20-64 years and >=65 years, 40.6%, 86.5% and 92.2% had primary series, respectively. Among adults, the booster uptake was 47.3% and 75.8% for those aged 20-64 years and >= 65 years, respectively. Among those with confirmed COVID-19, regardless of vaccination status, 87% were being symptomatic and 1.7% were hospitalized (3.8% in aged <5 years, 4.2% in 5-19 years, 34.3% in 20-64 years and 57.6% in >= 65 years). Among hospitalized patients, 32,6% were admitted to ICU and 80% required mechanical ventilation support. The average cost per day in normal wards and ICU without ventilation was R$291,89 and R$923,90, respectively. Conclusion(s): Our results quantify the public health and economic burden of COVID-19 in Brazil, suggesting substantial healthcare resources required to manage the COVID-19 pandemic.Copyright © 2023

Healthcare Resource Utilization and Costs Associated with Acute COVID in Adult Patients Managed in the Community or Hospital Setting in England: A Population-Based Study

Objectives: The COVID pandemic has imposed significant direct medical cost and resource use burden on healthcare systems. This study described the patient demographic and clinical characteristics, healthcare resource utilization and costs associated with acute COVID in adults in England. Method(s): This population-based retrospective study used linked primary care (Clinical Practice Research Datalink, CPRD, Aurum) and secondary care (Hospital Episode Statistics) data to identify: 1) hospitalized (admitted within 12 weeks of a positive COVID-19 PCR test between August 2020 and March 2021) and 2) non-hospitalized patients (positive test between August 2020 and January 2022 and managed in the community). Hospitalization and primary care costs, 12 weeks after COVID diagnosis, were calculated using 2021 UK healthcare reference costs. Result(s): We identified 1,706,368 adult COVID cases. For hospitalized (n=13,105) and non-hospitalized (n=1,693,263) cohorts, 84% and 41% considered high risk for severe COVID using PANORAMIC criteria and 41% and 13% using the UKHSA's Green Book for prioritized immunization groups, respectively. Among hospitalized cases, median (IQR) length of stay was 5 (2-7), 6 (4-10), 8 (5-14) days for 18-49 years, 50-64 years and >= 65 years, respectively;6% required mechanical ventilation support, and median (IQR) healthcare costs (critical care cost excluded) per-finished consultant episode due to COVID increased with age (18-49 years: 4364 (1362-4471), 50-64 years: 4379 (4364-5800), 65-74 years: 4395 (4364-5800), 75-84 years: 4473 (4364-5800) and 85+ years: 5800 (4370-5807). Among non-hospitalized cases, older adults were more likely to seek GP consultations (13% of persons age 85+, 9% age 75-84, 7% age 65-74, 5% age 50-64, 3% age 18-49). Of those with at least 1 GP visit, the median primary care consultation total cost in the non-hospitalized cohort was 16 (IQR 16-31). Conclusion(s): Our results quantify the substantial economic burden required to manage adult patients in the acute phase of COVID in England.Copyright © 2023

Evaluation of COVID-19 Vaccines in Primary Prevention Against Infections and Reduction in Severity of Illness Following the Outbreak of Sars-Cov-2 Omicron Variant in Shanghai

Objectives: To evaluate COVID-19 vaccines in primary prevention against infections and lessening the severity of illness following the most recent outbreak of the SARS-CoV-2 Omicron variant in Shanghai. Method(s): To investigate whether inactivated vaccines were effective in protecting against COVID-19 infections, we estimated the odds ratio (OR) of the vaccination in COVID-19 cases vs. matched community-based healthy controls. To evaluate the potential benefits of vaccination in lowering the risk of symptomatic infection (vs. asymptomatic), we estimated the relative risk (RR) of symptomatic infections among diagnosed patients. We also applied the multivariate stepwise Logistic regression analyses to measure the risk of disease severity (symptomatic vs. asymptomatic and moderate/severe vs. mild) in COVID-19 patient cohort with vaccination status as an independent variable while controlling for potential confounding factors. Result(s): Out of the 153,544 COVID-19 patients included in the analysis, 118,124 (76.9%) patients had been vaccinated and 143,225(93.3%) were asymptomatic patients. Of the 10,319 symptomatic patients, 10,031(97.2%), 281(2.7%) and 7(0.1%) experienced mild, moderate, and severe infections, respectively. There is no evidence that the vaccination helped protect from infections (OR=0.82, p=0.613). The vaccination, however, offered a small but significant protection against symptomatic infections (RR=0.92, p < 0.001) and halved the risk of moderate/severe infections (OR=0.48, 95% CI: 0.37 - 0.61). Older age (> 60 years) and malignant tumors were significantly associated with moderate/severe infections. Gender also appeared to be a risk factor for symptomatic infections, with females being associated with a lower risk for moderate/severe illness. Conclusion(s): Inactivated COVID-19 vaccines helped provide a small but significant protection against symptomatic infections and halved risk of moderate/severe illness among symptomatic patients. The vaccination was not effective in blocking COVID-19 Omicron variant community spread.Copyright © 2023

Clinical Characteristics of Patients with Sars-Cov-2 Omicron Variant and COVID-19 Vaccination with Clinical Outcome Findings in Shanghai, China: A Single Center, Retrospective, Observational Study

Objectives: This study aimed to determine disease severity, clinical features, clinical outcome in hospitalized patients with the Omicron variant and evaluate the effectiveness of one-dose, two-dose, and three-dose inactivated vaccines in reducing viral loads, disease course, ICU admissions and severe diseases. Method(s): Retrospective cohort analysis was performed on 5,170 adult patients (>=18 years) identified as severe acute respiratory syndrome coronavirus 2 positive with Reverse Transcription Polymerase Chain Reaction admitted at Shanghai Medical Center for Gerontology between March 2022 and June 2022. COVID-19 vaccination effectiveness was assessed using logistic regression models evaluating the association between the risk of vaccination and clinical outcomes, adjusting for confounders. Result(s): Among 5,170 enrolled patients, the median age was 53 years, and 2,861 (55.3%) were male. 71.0% were mild COVID-19 cases, and cough (1,137 [22.0%]), fever (592 [11.5%]), sore throat (510 [9.9%]), and fatigue (334 [6.5%]) were the most common symptoms on the patient's first admission. Ct values increased generally over time and 27.1% patients experienced a high viral load (Ct value< 20) during their stay. 105(2.0%) of these patients were transferred to the intensive care unit after admission. 97.1% patients were cured or showed an improvement in symptoms and 0.9% died in hospital. The median length of hospital stay was 8.7+/-4.5 days. In multivariate logistic analysis, booster vaccination can significantly reduce ICU admissions and decrease the severity of COVID-19 outcome when compared with less doses of vaccine (OR=0.75, 95%CI, 0.62-0.91, P<=0.005;OR=0.99, 95%CI, 0.99-1.00, p<0.001). Conclusion(s): In summary, the most of patients who contracted SARSCoV-2 omicron variant had mild clinical features and patients with vaccination took less time to lower viral loads. As the COVID-19 pandemic progressed, an older and less vaccinated population was associated with higher risk for ICU admission and severe disease.Copyright © 2023

Caesarean section in critically unwell peri-partum patients with COVID-19: A tertiary centre's experience

Introduction: The COVID-19 pandemic has required clinical teams to function with an unprecedented amount of uncertainty, balancing complex risks and benefits in a highly fluid environment. This is especially the case when considering the delivery of a pregnant woman critically unwell with COVID-19. This is one maternal critical care team's reflections on establishing best practice and a shared mental model when undertaking a Caesarean section in critically unwell patients with COVID-19. Objective(s): We describe our experience of balancing the risks and streamlining the process of this high-risk intervention. Method(s): We used our standard clinical governance forums across four specialties (Obstetrics, Intensive care, Anaesthetics and Neonatology) to identify key challenges and learning points. We developed a working group to combine our learning and develop a shared mental model across the involved teams. Result(s): 1. The decision to deliver must be multidisciplinary involving Obstetrics, Intensive care, Anaesthetics, Neonatology and the patient according to their capacity to participate. The existing structure of twice daily ITU ward rounds could be leveraged as a 'pause' moment to consider the need for imminent delivery and review the risk-benefit balance of continued enhanced pharmacological thromboprophylaxis. 2. We identified a range of scenarios that our teams might be exposed to: 3. Perimortem Caesarean section 4. Critically unwell - unsafe to move to theatre 5. Critically unwell - safe to move to theatre 6. Recreating an obstetric theatre in the ICU Advantages Avoids moving a critically unstable patient, although our experience is increasing moving patients for ECMO. Some forms of maximal non-invasive therapy such as High Flow Nasal Oxygen may require interruption to move to theatre with resultant risk of harm or be difficult to continue in transport mode through a bulky ICU ventilator e.g. CPAP Disadvantages Significant logistics and coordination burden: multiple items of specialist equipment needing to be brought to the ICU. Human factors burden: performing a caesarean section in an unfamiliar environment is a significant increase in cognitive load for participating teams. Environmental factors: ICU side rooms may offer limited space vs the need to control the space if performed on an open unit. Delivering a Neonate into a COVID bubble. Conclusion(s): Developing a shared mental model across the key teams involved in delivering an emergency caesarean section in this cohort of critically unwell patients has enabled our group to own a common understanding of the key decisions and risks involved. We recommend a patient centred MDT decision making model, with a structure for regular reassessment by senior members of the teams involved. In most circumstances the human factors and logistical burden of recreating an operating theatre in the ICU outweighs the risk of transport to theatre. Pre-defined checklists and action cards mitigate the cognitive and logistical burden when multiple teams do perform an operative delivery in ICU. Action cards highlight key aspects of routine obstetric care to be replicated in the ICU environment.

Impact of the COVID-19 pandemic on patients with osteogenesis imperfecta

OBJECTIVES: On March 11, 2020, the WHO classified COVID-19 as a global pandemic. Measures to quell the pandemic included limiting non-essential activities including clinic visits and procedures. It is unclear if individuals with OI had disruptions in their access to healthcare or medications, and if such disruptions affected patients' symptoms. METHOD(S): A REDCap survey was distributed through the OI Foundation on August 31. Surveys completed through September 11 by individuals with OI or their caregiver are included in this analysis. Participants were asked to compare their symptoms and access to healthcare during the first 4 months of the pandemic to the 4 months before the pandemic. RESULT(S): 85 surveys were completed, and 6 were partially completed. The median age of participants was 40 years;35% were children. 32% of participants self-identified as having severe OI. Although most reported no changes in bone pain or fractures, 46% reported they were less likely to seek emergency medical care to treat a fracture, while 33% reported they were more likely to treat fractures at home (Fig 1A). There were delays in accessing all services, with greatest delays accessing dentistry (74%) and aquatic therapy (84%) (Fig 1B). 36% of participants receiving bisphosphonate infusions had delayed infusions because of the pandemic (Fig 1C). Of note, 50% of planned surgeries were delayed. CONCLUSION(S): Although many individuals with OI and their caregivers reported delays in accessing bone-related services/clinics during this 4-month period, there was not a concomitant increase in reported symptoms. This may have related to shelter-in-place restrictions and decreased activity. Limitations of this study include small sample size and potential selection bias because responses were obtained only from OIF members. To address these limitations, we are distributing the survey through healthcare providers of individuals with OI across major regions of the US from a variety of practice types including endocrine, orthopedics and multidisciplinary clinics. Furthermore, as the COVID-19 pandemic continues, we hope that this survey will provide information to address what aspects of healthcare may be in greatest need, as well as the modality through which services may be met. (Figure Presented).

Impacts of COVID-19 on proton therapy - Shaping the future of patient selection

Objectives: This scoping review aimed to determine whether the COVID-19 pandemic influenced any modifications to patient selection methods or prioritisation and services provided by proton therapy centres. Method(s): This review was conducted based on the PRISMA methodology and Joanna Briggs Institute scoping review guidelines.1,2 A literature search was performed in Medline, Embase, Web Of Science and Scopus as well as grey literature. Keywords including "COVID-19" and "Proton Therapy" were used. Articles published from 1 January 2020 in English were included. In total, 138 studies were identified of which 14 articles met the inclusion criteria. A scoping review design was chosen to capture the full extent of information published relating to the aim. Result(s): Six of 14 articles included statements regarding treatment of COVID-19 patients. Three publications recommended deferred or alternative treatment, two indicated to treat urgent/emergency patients and one reported continuous treatment for infectious patients. Recurring impacts on PT provision included more frequent use of alternative therapies, reduced referrals, delayed treatment starts and CT simulation, change in treatment volume and staffing limitations due to pandemic restrictions. Consequently, telehealth consults, remote work, reduction in patient visitors, screening procedures and rigorous cleaning protocols were recommended. Discussion/Conclusion: Few publications detailed patient selection or workflow methods used during the pandemic. Further research is needed to obtain more detailed information regarding current global patient selection methods in proton therapy, collecting this data could aid in future planning for proton therapy in Australia.

The roles of suicide-related rumination and COVID-19 in suicidal ideation and behaviours: Data from a large-scale youth epidemiological sample in Hong Kong

Suicide remains to be one of the leading causes of death amongst young people worldwide. Help-seeking, however, remains disproportionately suboptimal in the youth population. Identifying more effective and less stigmatizing markers of suicidal ideation and behaviours can be important for improving early engagement and intervention work. We therefore examined the prevalence of suicidal ideation, plan, and attempt in a large epidemiological youth sample in Hong Kong (n = 2540) during the period of 2019-2021, as well as the factors associated with each of these outcomes using separate multivariable logistic regression models. In this sample, the 12-month prevalence of suicidal ideation, plan, and attempt was 20.0%, 4.6%, and 1.3%, respectively. In particular, we found 'suicide-related rumination' to be amongst the only factor that was significant for all three outcomes (p < .010). Using a two-stage approach (i.e., selecting only those with suicidal ideation), we found that suicide-related rumination, poorer cognitive ability, and 12-month major depressive episode were specifically associated with 12-month suicide plan, while environmental factors, including COVID-19 stressors, personal life stressors, poorer family relationships, as well as non-suicidal selfharm, were specifically associated with 12-month suicide attempt. A two-stage approach should be considered in future interventions targeting youth suicide. Suicide-related rumination may be an important marker of overall suicidal risk. The role of environmental stressors in addition to intrinsic vulnerability also need to be emphasized to best support young people at risk.

Stress reactions and health problems in hospital personnel during the COVID-19 pandemic-A longitudinal, multicenter study

Background: The overarching aim of the study was to (1) investigate how working with COVID-19 patients has impacted work environment, and (2) to identify how factors in the work environment impact adverse health outcomes among hospital personnel (HP), throughout the four waves of the pandemic. Material(s) and Method(s): In a web-based survey altogether 2472 HP participated from four large university hospitals in Norway, whereof N = 680 in April-June 2020 (T1), N = 1073 in December-January 2020/2021 (T2), N = 818 in April-May 2021 (T3), and N = 972 in December 2021-February 2022 (T4). At each time point participants reported on pandemic related work tasks, work environment and adverse health outcomes. Somatic symptoms, psychological distress, posttraumatic stress symptoms and burnout served as outcomes of multivariable linear regression models. The percentage of responders involved in ICU treatment of COVID-19 patients varied between 21% and 40% from T1-T4. Result(s): Reported stressors altered in strength during the 4 waves. Preliminary results indicate that exposure to patients with COVID-19 was associated with more frequent experience of work environmental factors. Compared to colleagues not working with patients with COVID-19 HP reported challenges related to professional competency and training, predictability in teams and work environment, manageable workload, adequate help and support for work stress management, user-friendliness of Personal Protection Equipment and infection protection safety. Furthermore, these environmental factors were associated with symptoms of psychological unhealth on at least one timepoint. Conclusion(s): The results may help guide organizational efforts to maintain professional competency and to reduce stress more efficiently among hospital personnel at different stages in response to long-term crises.

Acute or chronic? Failing left ventricle in a 34 year old

Submission content Introduction: An unusual case of a very young patient without previously known cardiac disease presenting with severe left ventricular failure, detected by a point of care echocardiogram. Main Body: A 34 year old previously well man was brought to hospital after seeing his general practitioner with one month of progressive shortness of breath on exertion. This began around the time the patient received his second covid-19 vaccination. He was sleeping in a chair as he was unable to lie flat. Abnormal observations led the GP to call an ambulance. In the emergency department, the patient required oxygen 5L/min to maintain SpO2 >94%, but he was not in respiratory distress at rest. Blood pressure was 92/53mmHg, mean 67mmHg. Point of care testing for COVID-19 was negative. He was alert, with warm peripheries. Lactate was 1.0mmol/L and he was producing more than 0.5ml/kg/hr of urine. There was no ankle swelling. ECG showed sinus tachycardia. He underwent CT pulmonary angiography which demonstrated no pulmonary embolus, but there was bilateral pulmonary edema. Troponin was 17ng/l, BNP was 2700pg/ml. Furosemide 40mg was given intravenously by the general medical team. Critical care outreach asked for an urgent intensivist review given the highly unusual diagnosis of pulmonary edema in a man of this age. An immediate FUSIC Heart scan identified a dilated left ventricle with end diastolic diameter 7cm and severe global systolic impairment. The right ventricle was not severely impaired, with TAPSE 18mm. There was no significant pericardial effusion. Multiple B lines and trace pulmonary effusions were identified at the lung bases. The patient was urgently discussed with the regional cardiac unit in case of further deterioration, basic images were shared via a cloud system. A potential diagnosis of vaccination-associated myocarditis was considered,1 but in view of the low troponin, the presentation was felt most likely to represent decompensated chronic dilated cardiomyopathy. The patient disclosed a family history of early cardiac death in males. Aggressive diuresis was commenced. The patient was admitted to a monitored bed given the potential risk of arrhythmia or further haemodynamic deterioration. Advice was given that in the event of worsening hypotension, fluids should not be administered but the cardiac centre should be contacted immediately. Formal echocardiography confirmed the POCUS findings, with ejection fraction <35%. He was initiated on ACE inhibitors and beta adrenergic blockade. His symptoms improved and he was able to return home and to work, and is currently undergoing further investigations to establish the etiology of his condition. Conclusion(s): Early echocardiography provided early evidence of a cardiac cause for the patient's presentation and highlighted the severity of the underlying pathology. This directed early aggressive diuresis and safety-netting by virtue of discussion with a tertiary cardiac centre whilst it was established whether this was an acute or decompensated chronic pathology. Ultrasound findings: PLAX, PSAX and A4Ch views demonstrating a severely dilated (7cm end diastolic diameter) left ventricle with global severe systolic impairment.

Supporting practice nurses in diabetes, revalidation and appraisal programme: A practical course for new practice nurses (PN) undertaken diabetes care

Aims: To upskilling PN to undertake diabetes clinics and ensure high quality healthcare for our patients by maintain the nursing workforce in primary care. Method(s): The programme was delivered over two days, one month apart with follow up day's at six months and 1 year. During Covid-19 we had adapted the session to 4 half days over a 2 month period and are waiting to do our follow up day face to face. The programme included a broad range of topics and skills required to undertake diabetes clinics. Result(s): 13 PN attended from different geographical areas in our healthboard;having a various amount of experience as a PN from 16 yrs to 1 month but limited diabetes experience. Through anonymous questionnaire responses we showed an improvement in confidence across a broad range of core skills and management. Asked if they felt individually confident pre and post course -new diabetes diagnosis (38% to 92%), hypoglycaemia (53% to 92%), pens and meters (8% to 76%), sick day rules (30% to 84%), foot screening (61% to 92%) and advising on oral medication (30% no confidence improving to 84%). Increasing PN knowledge will ultimately improve patient's care thus reducing the risk of complications. preceptorship throught the course was offered by experience Diabetes Specialist Nurses. Conclusion(s): Even in these challenging times we have to maintain a skilled workforce by delivering education and preceptorship to PN. The Supporting prActice Nurses in Diabetes, Revalidation and Appraisal programme provides PN the tools to undertake diabetes clinics with confidence and ensure excellent patient care.

Impact on glycaemic outcomes of transitioning from in-person to virtual FreeStyle Libre onboarding during the Covid-19 pandemic

Background and aims: Onboarding of the FreeStyle Libre, an intermittently scanned continuous glucose monitoring (isCGM) device, was pre-dominantly conducted in-person prior to the Covid-19 pandemic. However, onboarding rapidly become virtual due to enforced social distancing restrictions. This audit aimed to determine if onboarding method impacted on glycaemic outcomes and engagement statistics in people living with diabetes (pwD). Method(s): PwD who started FreeStyle Libre between January 2019 and March 2022, had their mode of onboarding recorded and had >=70% data were identified and included within the audit. Glycaemic indices and engagement statistics (previous 90 day averages) were obtained from LibreView (Abbott, USA) three months after the last person was onboarded, and compared using linear models, adjusting for FreeStyle Libre duration, %active (where appropriate), age and sex. Result(s): From 1007 eligible participants (in-person 44% [n = 445];virtual 56% [n = 562]), FreeStyle Libre usage duration was greater for those onboarded in-person vs. virtually (974[891,1101) vs. 420[280,564] days [p < 0.001]). There were no significant differences in glycaemic or engagement indices between in-person and virtual onboarding methods: average glucose (10[9,11]) vs. 10[9,11])mmol/l), %time very-low (<3.0mmol/l, 0[0,1]) vs. 0[0,1]%), %time low (3.0-3.8mmol/ l, 2[1,4] vs. 2[1,4]), %time in range (3.9-10.0mmol/ l, 54[+/-17] vs. 53[+/-19]%), %time high (10.1-13.9mmol/ l, 27[21,31]) vs. 26[21,31]%), %time very-high (>13.9mmol/l, 14[6,24] vs. 15[7,26]%), %active (96[90,100] vs. 94[87,99]%) or scans/day (11[8,15] vs. 10[7,14]). Conclusion(s): There were no differences in glycaemic outcomes or engagement indices between pwD between onboarding methods. Virtual onboarding using online videos for isCGM is as equally effective as face to face.

Creating a smart classroom on intensive care using assisted reality technology

Introduction: Medical students receive relatively little exposure to intensive care medicine throughout their undergraduate training in comparison to other specialties. The COVID-19 pandemic further hindered students' exposure with entrance to intensive care units (ICU) limited to conserve personal protective equipment (PPE) and reduce the risk of virus spread. To address this problem, this study explored the use of assisted reality technology to create a smart classroom whereby medical students can experience intensive care medicine with the COVID-19 risks mitigated. There is existing literature describing the use of live streaming ward rounds using wearable technology to teach medical students, however, we believe this is the first time assisted reality technology has been harnessed to develop a teaching curriculum on intensive care.1 Objectives: This study aimed to assess the feasibility of using a wearable headset with assisted reality technology to live stream intensive care teaching to remotely based medical students. Method(s): Three intensive care teaching sessions were live streamed to three groups of medical students using the AMA XpertEye wearable glasses. The teaching session focused on the intensive care bed space and equipment as well as the assessment of a critically unwell intensive care patient. Two educators were required to facilitate the optimum learning environment. One educator wore the assisted reality technology glasses on the ICU whilst the other educator remained with the students to facilitate group discussion. The educators had the means to communicate via inbuilt technology on the glasses. Feedback from students was collected using the evaluation of technology-enhanced learning materials (ETELM).2 Results: The response rate for the ETELM survey was 100%. Students strongly agreed that the session was well organised, relevant and that the navigation of technology-based components was logical and efficient. 'There was a strong instructor presence and personal touch to the session' returned the strongest positive response. 'This session will change my practice' received the most varied response from students, potentially due to their stage in undergraduate training and distance from actual clinical practice. Students strongly disagreed that their learning was affected by technology issues. Educators reported problems with securing a patient appropriate to be involved alongside the busy clinical demands of the ICU. Facilitation by trained educators was crucial to ensure the teaching sessions were high quality. Conclusion(s): The use of smart classrooms on intensive care using assisted reality technology was very well received by medical students and educators. The main limitations included the necessity to balance the delivery of teaching alongside the clinical demands of the unit, however this is arguably the case with most forms of clinical teaching. There is the potential to continue using smart classrooms in the post-pandemic period, as they provide an open and safe platform for students to explore intensive care medicine and to ask questions that they may feel less able to raise in the busy clinical environment.

Providing culturally responsible health care to Pacific Islander communities: The creation of a cultural competency training for healthcare professionals

Cultural competency is the ability to respectfully engage, understand, and communicate through conscientious interaction, enabling effective work and meaningful relationships in cross-cultural situations. Cultural competency recognizes the importance for organizations of participants' diverse social and cultural values, beliefs, and behaviors, and has gained attention because it can bridge health perspectives, understanding, and respect between health professionals and patients. There remains a need for cultural competency in healthcare as disparities persist across the U.S. in racial and ethnic minority groups who experience worse health outcomes and lower healthcare quality than the general public. Therefore, a cultural competency training curriculum was created using various resources to improve interactions between Pacific Islander patients and healthcare professionals. This training helps to reduce racial/ethnic disparities in healthcare by encouraging mutual understanding and improving patient satisfaction, adherence to medical instructions, and overall health outcomes by highlighting patient-centered care as a result of utilizing components of cultural competency. To improve patient experiences in Hawai'i, healthcare professionals need the tools to better interact with patients from different cultures, such as Pacific Islanders. This training provides healthcare professionals with culturally-based content for improving cultural competence techniques for interacting with Pacific Island patients. This training was pilot tested with key stakeholders from community organizations and Cancer Center faculty/staff. Local health clinics, providers, and practices will have the opportunity to participate in this training through a Zoombased electronic training format and be provided with three continuing medical education credits. The initial delivery of the training was intended for in-person sessions;however, a virtual format was adapted due to the COVID-19 pandemic and subsequent social distancing regulations. Healthcare providers are provided pre-training resources, a pre- and post-test, and a course evaluation to determine the validity of training objectives. To date, two Federally Qualified Health Centers have been provided the training, n=60, as well as one Cancer Health Equity Partnerships' Scientific Workshop, n=40. For attendees, the analysis of correct responses from the pretest to post-test showed a significant improvement on 6 of the 12 questions. Respondents also agreed that the training resources aligned with the course objectives. Improved patient interactions from this training can help support better patient outcomes, adherence to medical advice regarding cancer screenings, and many other aspects of improving health equity for Pacific Islanders.

The factors associated with increased risk of hospitalisation in people with diabetes following SARS-CoV- 2 infection: A national replication study

Aim: People with type 1 or type 2 diabetes have a higher hospital admission rate following Covid-19 infection. This study aims to determine the degree to which the results of a previous study in Greater Manchester (GM) could be replicated in national-level data for England. Method(s): We focussed on the univariable regression analysis, which shows the association between admission and Covid-19 infection in people with diabetes. Modelling was conducted using logistic regression on data from the Covid-IMPACT database. Odds ratios were compared descriptively with the previous study. Result(s): In people with type 2 diabetes, factors associated with an increased risk of hospitalisation similar to the previous study were: older age, male sex, higher social deprivation, higher body mass index (BMI), higher cholesterol, lower eGFR, taking an ACE-inhibitor/ ARB, not taking metformin, and having asthma or hypertension. Patients with COPD, and those taking aspirin or clopidogrel also had increased risk, but the national data showed a greater risk (GM COPD odds ratio 1.89 [1.63-2.19] vs national 2.34 [2.28-2.40] / aspirin 1.49 [1.34-1.66] vs 1.66 [1.63-1.70] / clopidogrel 1.71 [1.47-1.98] vs 1.99 [1.94-2.04]). Similar results were observed in patients with type 1 diabetes. However, due to the increase in sample size, many factors which were previously not statistically significant have become significant, such as in type 2 diabetes BMI, low HDL-cholesterol. Conclusion(s): We have successfully replicated the methods, results and conclusions of our previous study in relation to factors associated with increased risk of hospital admission in diabetes individuals. Regional databases are suitable for large cohort studies, and in this instance produced similar results to a national database, validating our previous findings.

Salt steps and sugar checks - Making arterial line use safer in our trust

Introduction: Arterial lines are used within our intensive care unit to allow invasive blood pressure monitoring and regular blood gas analysis. Inadvertent use of dextrose containing fluids in the flush have been associated with falsely high glucose readings. When these are acted on with insulin, it can cause devastating hypoglycaemic brain injury. There have been a number of deaths and other incidents relating to the wrong fluid being used in arterial line set up reported within the UK in recent years. In 2014 the AAGBI released a safety guideline on the use of arterial lines specifically to reduce to the risk of hypoglycaemic brain injury. Objective(s): Our objective was to ensure that 100% of arterial lines in use within Royal Victoria Hospital's intensive care unit were compliant with our trust policy on the management of arterial lines. Method(s): We audited our intensive care unit's compliance with our trust policy and found that we were 80% compliant. We formed a multi-disciplinary arterial line working group in order to tackle the problem. Our quality improvement project consisted of two main approaches: 1. To educate staff on how to manage arterial lines correctly. We divided the management of arterial lines into S.A.L.T steps (a 7 step bundle on "Setting up an Arterial Line Transducer") and SUGAR checks ( a series of red flag moments to prompt staff to review the patient prior to starting or increasing insulin administration).We developed educational posters for key areas in ICU and presented our findings at departmental meetings. 2. To change the system, in order to make it easier to do the right thing. We developed a Universal Adult Arterial Pack (UAAP) containing key components in the setup of an arterial line. This also included aide memoires for the S.A.L.T steps and SUGAR checks. In order to measure the effect of these changes, we: 1. Audited compliance on a regular basis. 2. Monitored serious bundle breaches ( for example no label, wrong fluid used) 3. Assessed usage of the UAAP. Result(s): 1. Bundle compliance improved during the first half of 2021, however then reduced in the second half with the number of serious bundle breaches increasing. This coincided with COVID surge 4 - associated with reduced nursing ratios and staff redeployment. 2. UAAP usage increased throughout the project, from an average of 6 to 9 per day. 86% of staff found the packs useful and 85% thought that they reduced the potential for error. Conclusion(s): The presence of a policy does not ensure that staff will know about it or adhere to it. Although we have not yet achieved our target of 100% compliance, we have seen evidence of how our project has the potential to do so in the near future. We aim to roll out our new e-learning module for staff education, manufacture our UAAP on a bigger scale, and disseminate the project to other departments within the trust.

Association of apolipoprotein E4 to the number of cerebral microbleeds in patients recovered from COVID-19

Background: COVID-19 has been associated with cerebral microbleeds (CMB). Previously, an association of ApoE4 with COVID-19 severity and CMBs in autopsy was found. In this study, we investigated if carrying the Apoe4 allele relates to the number of CMBs in magnetic resonance imaging (MRI) in patients recovered from COVID-19. Material(s) and Method(s): Adult patients recovered from COVID-19 and a control group without a history of COVID-19 was recruited. Exclusion criteria were major neurologic disease, developmental disability or pregnancy. The participants underwent brain MRI 6 months after infection, and a blinded neuroradiologist analyzed the findings. ApoE was genotyped using a microarray. Statistical analysis was performed using the statistical software R. A negative binomial model was chosen based on the distribution of CMBs. Result(s): Of the 216 subjects that underwent MRI, 168 consented to genetic testing, additionally 2 patients were excluded due to extensive CMBs and 1 due to diffuse axonal injury. We included 113 COVID-19 patients (49 ICU-treated, 29 ward-treated and 35 home-isolated) and 52 controls. The most prevalent comorbidities were hypertension, asthma and diabetes. CMBs was found in 47 subjects, with the number of CMBs ranging from 0 to 26. The ApoeE4 allele was carried by 37%, equally distributed among the groups. After adjustment, age (aRR = 1.06, p = 0.007) and COVID-19 (aRR = 2.59, p = 0.038) were independently associated with CMBs. The ApoE4 allele (aRR = 2.16, p = 0.07, CI = 0.94-5.10) was not significant. Conclusion(s): Age and previous COVID-19, but not possession of the ApoeE4 allele, were independently associated with the number of CMBs.