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.

Restoring quality of an ECMO education programmme from the aftermath of COVID-19 pandemic: Preliminary results from a continuous quality improvement process

Objectives: Extracorporeal membrane oxygenation (ECMO) is a complex life support modality. To appropriately educate ECMO clinicians, a comprehensive program is required. However, there is no universal ECMO education (EE) program exclusively for intensive care unit Registered Nurses (RNs). Moreover, with the recent Coronavirus Disease 2019 (COVID-19) pandemic, the existing nursing shortage and the ability of ECMO programs to maintain an established EE program worsened. This continuous quality improvement (CQI) aims to reestablish the quality of an EE program at a large academic medical center at one of the past pandemic epicenters. Method(s): A CQI process with the Plan-Do-Study-Act (PDSA) cycle and Ishikawa diagram for root cause analysis (RCA), intervention implementation from July 2022 to June 2023 Results: The RCA revealed intrahospital pandemicrelated restrictions for employee gathering, EE instructor unavailability, increased nursing turnover, increased nursing shortage, and incomplete recordkeeping of ECMO educational activity (EEA) RN attendance as dominant factors disrupting the established EE processes. Six interventions were implemented, with one added in later: 1. Schedule 1 Certification Lecture Day/Quarter (Q), 1 Re-Certification Lecture/Q, and 1 Circuit Skills Class/ month, and 1 Simulation Lab/month 2. Reserve an education room for all EE activities, as COVID-19 policies allow 3. Increase the number of EE instructors 4. Increase Nursing Leadership-ECMO Manager collaboration for optimal RN signup 5. Optimize EEA schedule to help balance RN staffing needs 6. Develop a Master ECMO Folder in Google Drive and maintain updated attendance Five interventions showed positive preliminary results, whereas it was too soon for any conclusion for one (Table 1). Conclusion(s): While preliminary, the achieved results justify that restoring the quality of an ECMO education program after the negative impact of the recent pandemic is possible. However, final results are necessary to infer the effectiveness of each intervention. (Figure Presented).

Preliminary results from phase 2 of CC-92480- MM- 001: Mezigdomide plus dexamethasone in relapsed/refractory multiple myeloma (RRMM)

In phase 1 of CC-92480- MM- 001 (NCT03374085), the recommended phase 2 dose (RP2D) of mezigdomide plus dexamethasone (MEZI-d) was selected at 1 mg once daily for 21/28 days. Here we report preliminary results from the MEZI-d dose-expansion cohort in patients with heavily pretreated RRMM. Key eligibility criteria were: RRMM;>=3 prior lines of therapy;disease progression <=60 days of last myeloma therapy;refractoriness to lenalidomide/pomalidomide, a proteasome inhibitor, a glucocorticoid, and an anti-CD38 monoclonal antibody. Oral mezigdomide 1 mg was given on days 1-21 of each 28-day cycle, plus weekly dexamethasone (40 mg;20 mg if >75 years of age). Primary objective was to evaluate efficacy (overall response rate [ORR]);secondary objectives included safety/tolerability and additional efficacy assessments. Pharmacodynamics was an exploratory objective. As of 16/Sep/2022, 101 patients had received MEZI-d at the RP2D. Median age was 67 (range 42-85) years, median time since initial diagnosis was 7.4 (1.1-37.0) years;39.6% of patients had plasmacytomas and 37/101 patients had high-risk cytogenetics (56/101 not evaluable). Median number of prior regimens was 6 (3-15);prior therapies included stem cell transplantation (77.2%) and anti-BCMA therapy (29.7%). All patients were refractory to last myeloma regimen and triple-class refractory. Median follow-up was 7.5 (0.5-21.9) months, with a median of 4 (1-20) cycles;10.0% of patients continued treatment;progressive disease was the main reason for discontinuation (60.4%). ORR was 40.6% for all patients. Whilst data are not mature yet, median PFS was 4.4 (95% CI 3.0-5.5) months and median duration of response was 7.6 (95% CI 5.4-9.5) months. ORR was 30.0% in patients with plasmacytomas (N = 40) and 50.0% in patients with prior anti-BCMA therapy (N = 30). Ninety-one (91.1%) patients experienced a grade 3/4 treatment-emergent adverse event (TEAE). Most frequent hematologic grade 3/4 TEAEs were neutropenia (75.2%), anaemia (35.6%), and thrombocytopenia (27.7%);34.7% of patients had grade 3/4 infections, including grade 3/4 pneumonia (15.8%) and COVID-19 (7.0%). Occurrence of other grade 3/4 non-hematologic TEAEs was generally low. Due to TEAEs, 76.2% and 29.7% of patients had mezigdomide dose interruptions and reductions, respectively;90.1% of patients discontinued mezigdomide. Mezigdomide induced substrate degradation and increases in activated and proliferating T cells in patients, including those directly refractory to pomalidomide-based therapies. MEZI-d had a manageable safety profile with encouraging efficacy in patients with triple-class refractory RRMM, including patients with prior BCMA-targeted therapies. These results strongly support the continued development of mezigdomide in MM, and especially in combination.

Youth suicide risk and mental health post-COVID: An Australian perspective

Aims: Suicide is a leading cause of death for young people, and rates in Australia are increasing. The Australian city of Melbourne faced the toughest COVID-19 pandemic lockdown restrictions worldwide, which had a major impact on youth mental health. This study aimed to provide a snapshot into the mental health and suicide-related thoughts and behaviours of Australian Adolescents from Melbourne post the lockdowns. Method(s): Participants were 932 young people (Age M = 15.5, 53% female) recruited from high schools in Melbourne, Australia as part of a larger RCT. Participants completed measures of suicidal ideation (SIDAS) and behaviour (recent attempts and current plans), and depressive symptoms (PHQ-9). Result(s): Preliminary results indicate that 28% of participants experienced some level of suicidal ideation with 7% reporting severe suicidal ideation. Suicide attempts in the sample in the last 12 months (13%) and current plans (3%) were less common but still prevalent. In terms of depressive symptoms, the breakdown in the sample was 5% severe, 8% moderately severe, 18% moderate, 25% mild and 43% none to minimal with 1% not reporting. Data related to particular risk factors (e.g., years since the pandemic, gender, school etc.) along with implications for practice and policy will be presented at the conference. Conclusion(s): This study sheds light on the mental health and suiciderelated thoughts and behaviours of school-attending young people following COVID-19-related lockdowns in Australia. The high levels of suicidality and poor mental health in the cohort point to a need for targeted interventions and support for this group.

Pancreatic Stone Protein (PSP) as a predictive biomarker of multiple organ failure and clinical outcome

Background: COVID-19 syndrome is associated with high morbidity and mortality in haemodialyzed patients. Pancreatic Stone Protein (PSP) is an early biomarker of sepsis and a prognostic biomarker of disease severity in critically-ill patients and can be rapidly measured at the patient's bedside with a point-of-care-test from a small drop of whole blood. The aim of our pilot was to investigate PSP in patients requiring haemodialysis with SARS-CoV-2 infection, at different severities of COVID-19 disease. Method(s): Between February and July 2021, 23 patients (6 severe COVID-19 with Acute Kidney Injury, 6 moderate COVID-19 haemodialyzed, 2 haemodialyzed without COVID-19 and 3 healthy controls) were recruited at the University Hospital of Foggia for PSP evaluation. Biomarker's measurements were performed within 48 hours after admission or upon arrival for haemodialysis (pre-treatment). PSP was measured at the patient's bedside with "abioSCOPE", a point-of-care test capable of evaluating PSP levels in five minutes from a small drop (50mul) of whole blood or serum. Result(s): The preliminary results of this pilot study showed a trend for PSP to increase along with the severity of disease. In fact, serum PSP levels were significantly higher in Intensive Care Unit subjects than in COVID-19 negative haemodialysis subjects and controls (ANOVA p=0.032). Furthermore, PSP levels were significantly higher in subjects who died (p<0.017). Whether this increase is due to the kidney injury or COVID-19 disease remains unknown, and more research is needed to understand the relationship. Conclusion(s): Several clinical studies published in literature have shown the predictive value of PSP in the early identification of sepsis and severity of the clinical outcome. In our experience we have seen a trend for PSP to increase with disease severity also in COVID-19 patients. These results are preliminary, but PSP was significantly higher in patients who died, in accordance with the literature. This experience also has demonstrated the feasibility of a point of care system to be easily implemented in the unit and adopted by personnel and its design enables fast results and immediate decisions to be taken, especially in urgent situations.

Procedure Based Telehealth Utilization in General Surgery

Introduction: After COVID-19, telehealth (TH) capabilities expanded relaying patient satisfaction, time savings, and efficient access to care. We hypothesize standardized TH scheduling processes improves TH utilization without increasing adverse events (AE). Method(s): The Telehealth Utilization Quality Improvement Initiative was conducted from 8/2021-1/2022 in the general surgery clinic. 50 visits pre-implementation and 70 visits post-implementation were audited over the study period. Stakeholders were engaged including faculty, clinic coordinators, and administrative staff to identify current workflows and potential interventions, targeting outpatient elective procedures. Process mapping outlined current TH scheduling workflows. Outcomes such as percent TH scheduled in clinic, in addition to cost, and adverse patient events were collected post-implementation. Result(s): Preliminary data revealed 50 patients who underwent elective outpatient surgeries, all appropriate for TH postoperative follow-up visits. Overall, the pre-implementation TH scheduling rate was 32%. TH was schedule dafter surgery in the preintervention group. The intervention required TH postoperative appointments to be scheduled in clinic at the time of surgery scheduling with TH being the default postsurgical appointment for a standardized list of eligible procedures. After implementation, 95% of patients undergoing elective, outpatient general surgery procedures were scheduled for a TH visit with 83% of patients completing their follow up via TH.This resulted in increased revenue of $30,431 in billable visits due to increased clinic visit availability. No AE were seen. Conclusion(s): Standardizing TH scheduling based on procedure improves the utilization of TH in outpatient, elective general surgery procedures resulting in improved clinic efficiency, increased revenue, and no AE.

Keeping occupational possibilities in pandemic times: Perspectives of young adults experiencing a first episode and their mental health practitioners

Aims: (1) To describe how occupational possibilities of young adults experiencing a first episode of psychosis changed during the pandemic;(2) to describe how mental health practitioners, working in two first episode clinics, strived to assist their clients in maintaining a meaningful daily life during the COVID-19 pandemic. Method(s): This exploratory study used an interpretative descriptive design. Young adults (n = 6), attending a specialized clinic, participated in two semi-directed interviews: they explored how their daily lives changed during the pandemic, their (re)actions in light of the changes and which occupations were (im)possible to pursue. A focus group discussion with the practitioners will allow to explore the adjustments made to clinical practices to enrich young adults' daily lives. The interviews and focus groups were transcribed and analysed independently by two members of the research team, using a thematic analysis approach. Result(s): Preliminary results suggest that if some occupational possibilities were lost, many were transformed or newly envisioned by young adults. They engaged in occupations within existing niches. The presentation will also include the perspective of mental health practitioners, as focus groups will be concluded in early Winter 2023. Conclusion(s): This presentation offers a novel perspective on the daily lives of young adults during the pandemic, focusing on the nature of their occupational engagement, whilst considering how the context shaped their occupational possibilities. Likewise, it will document the innovative practices and challenges experienced by practitioners, as they strived to expand possibilities for their clients and to support their transition into adulthood.

COPD Exacerbation Profile in Chile: Preliminary Results from Integramedica Cohort 2018-2020

Objectives: To describe demographic characteristics, comorbidities, and exacerbations in a cohort of patients with COPD in Chile. Method(s): Retrospective cohort study using INTEGRAMEDICA (a network of ambulatory medical centers) electronic medical records of patients with COPD aged >=40 years at index with data available one year before (baseline) and after (follow-up) index. Index date was fixed at 28-Feb-2019 to avoid including data from the COVID-19 pandemic. Moderate and severe exacerbations were defined as prescription of systemic corticosteroid/antibiotics and emergency visit/hospitalization, respectively. Result(s): In total, 19,000 patients were included. In the baseline period, 86% (n=16,400) had no moderate or severe exacerbations (NMSE), 13% (n=2,503) had only moderate exacerbations (OME) and <1% (n=96) had >=1 severe exacerbation (SEV). Mean age/proportion of females was: 64 years/60% (total cohort), 65 years/59% (NMSE), 61 years/67% (OME) and 73 years/62% (SEV). The four most frequent comorbidities were: hypertension (total: 17.6%;NMSE: 16.2%;OME: 26.0%;SEV: 24.0%), asthma (total: 8.9%;NMSE: 7.8%;OME: 15.3%;SEV: 17.7%), diabetes type 1/2 (total: 6.3%;NMSE: 5.9%;OME: 9.1%;SEV: 7.3%) and congestive heart failure (total: 3.2%;NMSE: 3.2%;OME: 2.9%;SEV: 4.2%). The proportion of patients with >=1 moderate/severe exacerbation during follow-up was 14% (total), 10% (NMSE), 38% (OME) and 35% (SEV). The severe exacerbation rate was 2.00 per 1,000 person-years in the overall population and increased based on exacerbation history (NMSE: 0.91;OME: 1.60;SEV: 197.92) Conclusion(s): Preliminary results indicate that severe exacerbations were more frequent in patients with a history of SEV compared with patients with a history of OME or NMSE. In addition, comorbidities were more frequent in patients with a history of exacerbation. To improve patient health outcomes, strategies with a multisectoral approach should be prioritized as COPD can coexist with, and be aggravated by, other chronic comorbidities. Funding(s):GSK [209968].Copyright © 2023

Updated Real-World Safety of the Pfizer-BioNTech COVID-19 Vaccine in Pregnancy: Data from the Organization of Teratology Information Specialists (OTIS) Pregnancy Registry

Purpose: Preliminary data indicate that pregnant women infected with COVID-19 are at increased risk of pregnancy complications (US Centers for Disease Control and Prevention, October 2022). Information on the real-world safety of COVID-19 vaccination in pregnancy is essential. We sought to describe preliminary results for pregnancy status among pregnancy registry participants enrolled in an ongoing safety study of the Pfizer-BioNTech COVID-19 vaccine to date. Method(s): This study uses data from the Organization of Teratology Information Specialists (OTIS) Pregnancy Registry as part of the Vaccines and Medications in Pregnancy Surveillance System (VAMPSS) which enrolls pregnant women residing in the US or Canada. Data are captured through maternal interviews and the ion of medical records. The study population for this descriptive analysis includes Registry participants who met eligibility criteria on or after December 11, 2020, the date the US Food and Drug Administration granted emergency-use authorization for the Pfizer-BioNTech vaccine. The target sample size is 1,100 pregnant women who received any dose of the Pfizer-BioNTech vaccine from 30 days prior to the last menstrual period through the end of pregnancy, and 900 comparison women who received no COVID-19 vaccine in pregnancy. Result(s): Among pregnant women participating in the Registry between 11 December 2020 and 22 July 2022, 1,100/1,100 participants (100.0% of the target sample) were enrolled as part of the Pfizer-BioNTech COVID-19 vaccine exposure cohort, and 635/900 participants (70.6% of the target sample) were enrolled in the comparator cohort. As of 22 July 2022, 858 (78.0%) in the vaccine exposure cohort and 313 (34.8%) in the comparator cohort had completed pregnancies. Descriptive data indicated numerically similar percentages of pregnancies ending in at least one liveborn infant, spontaneous abortions, stillbirths, and elective terminations across the exposed cohort stratified by trimester of the earliest dose of the Pfizer-BioNTech COVID-19 vaccine received in pregnancy, and overall in the unexposed comparator cohort. Conclusion(s): Preliminary data have not identified any new safety concerns thus far for pregnant women who receive the Pfizer-BioNTech COVID-19 vaccine during pregnancy. Funding(s): This study was conducted as a collaboration between the University of California San Diego and Pfizer. Pfizer is the study sponsor.

Exploring the impact of one-to-one peer support on recovery processes in the early psychosis intervention programme (EPIP) in Singapore

Aims: Peers4Rs (Remembering Resilience, Respect and Recovery) was established within the Early Psychosis Intervention Programme (EPIP) in 2010 to promote client advocacy and recovery. Despite recommendations for peer support in early intervention services, there is a general lack of research on its impact. Current research evaluating peer support are heterogeneous in relation to interventions and outcomes, limiting research quality. This exploratory study aims to evaluate oneto- one peer support intervention on recovery processes in people with early psychosis in Singapore, during the COVID-19 period. Method(s): Data from 26 clients with first-episode psychosis (FEP), aged between 15 and 44 years, who were accepted into the service between 2021 and 2022, was included in the analysis. One-to-one peer support intervention was delivered over phone/video call or inperson by certified Peer Support Specialists (PSSs). The 22-item selfreport Process of Recovery Questionnaire (QPR) was administered at pre- and post-intervention. Paired-sample t-test was run. Result(s): Pre- and post- scores were compared before and after completing the one-to-one peer support intervention. On average, post scores (M = 62.77, SD = 7.60) were higher than pre scores (M = 49.31, SD = 12.07). This improvement, 13.46, 95% CI [9.26, 17.67], was statistically significant, t (25) = 6.59, p < .001, Cohen's d = 1.34. Conclusion(s): Based on preliminary results, clients with FEP grew in their recovery process through the one-to-one peer support intervention in EPIP. This finding is promising, given small sample sizes and limits in mode of contact during the pandemic, lending support to further discussions.

Preliminary analysis of the epidemiological effectiveness of COVID-19 vaccination in the Saratov Region

The new coronavirus infection (COVID-19) caused by the SARS-CoV-2 virus continues to spread rapidly worldwide, despite the increased prevention and treatment measures being taken. Vaccination is one of the most cost-effective and effective methods of preventing infectious diseases in the modern world, including one of the most effective methods of combating COVID-19. Over several centuries of history, vaccination has proven its effectiveness in saving people's lives, reducing the spread of infectious diseases among the population, as well as reducing mortality. The effectiveness of immunization against COVID-19 is an urgent problem at the moment, especially when it comes to vaccination. The aim of the work is to study the effect of vaccination on the incidence of a new coronavirus infection among residents of the Saratov Region. Material and methods. Methods of retrospective epidemiological analysis of trends in the epidemic process COVID-19 were used. The obtained materials were processed using methods of variational statistics (Excel program). The analysis was based on data from daily monitoring of laboratory diagnostic results (more than 1780 thousand PCR diagnostic studies were conducted during the epidemic), COVID-19 cases and deaths, taking into account the coverage of the population with preventive vaccinations. The statistical significance of the differences was assessed according to the Student's criterion. The differences were considered significant at t<=2. Results and discussion. As of June 30, 2021, more than 267 thousand people or 11% of the population of the Saratov region were fully vaccinated against COVID-19. There were no complications after the introduction of vaccines. In the structure of all medical immunobiological preparations that were immunized, the proportion of the vaccine "Gam-COVID-Vac" was 97.88%, "Epivaccorona" - 1.69% and "Covivac" - 0.43%. According to preliminary data, 361 of the vaccinated people were infected with SARS-CoV-2, of which: 255 (70.6%) had a mild course of the disease with manifestations of catarrhal syndrome, 84 (23.3%) had community-acquired pneumonia, 22 (6%) had no symptoms of the disease. No deaths have been registered among the vaccinated. The overall incidence of COVID-19 among vaccinated was 0.06%. The incidence rate of COVID-19 among the vaccinated population is 6.025+/-0.15 per 10 thousand people, which is significantly lower (t>2) than among the unvaccinated (103.8+/-0.63 per 10 thousand people), efficiency index - 17.23, epidemiological efficiency coefficient - 94.20% Conclusion. Insufficient coverage of the population of the Saratov Region with vaccination (as of June 30, 2021, 11% were fully vaccinated) does not allow to influence the reduction of the incidence of COVID-19. The high epidemiological effectiveness of COVID-19 vaccination of the adult population with domestic vaccines, including people over 65 years of age, has been revealed.Copyright © 2022 Geotar Media Publishing Group

Vaccination in Patients with Inflammatory Rheumatic Diseases: Preliminary Results of an International, Real-World Life Panlar's Register

Objectives: To evaluate vaccination among patients with inflammatory rheumatic diseases initiating disease-modifying antirheumatic drugs (DMARD) Methods: Data from the real-world life PANLAR's register of consecutive patients diagnosed with RA, PsA, and axSpa (2010 ACR-EULAR /2006 CASPAR-2009 ASAS) from Dec 2021 to Dec 2022 were analyzed. Prevalence of recommended vaccinations were compared between different inflammatory rheumatic diseases. Categorical variables were expressed as %. Tables were analyzed with chi2 or Fisher tests, continuous variables (median, IQR)with the Kruskal-Wallis test, according with the variables type. A p value <=0.05 was considered significant. Result(s): 608 patients were included. Among patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial Spondyloarthritis (axSpA) are presented in the table. RA and axSpA seemed to have lower vaccination rate of pneumococcal vaccines than PsA. (p = 0.045 for conjugate anti pneumococcal vaccine in RA vs PsA). A large percentage of the population was vaccinated against COVID-19. There was a high rate of influenza vaccination in all three diseases. Conclusion(s): In Latin America, anti-pneumococcal vaccination is low, especially in patients with RA and axSpA. For other vaccines there was an acceptable level of vaccination without differences between diseases.

Circular medicine. a paradigm of sustainability and resilience in education and professional development

Circular economy is a model of economic, social and environmental production and consumption, aimed to build a sustainable society in tune with the available resources. In the Brundtland Report, (1987, United Nations) sustainability it is defined as an approach focused on "meeting the needs of the present without compromising the ability of future generations to meet their own needs." The European Medical Association (EMA), that has currently more than 50 000 members, is involved in the advancement of health, pursuing educational and professional goals addressed to the quality of environment, lifestyle and civil society through a circular medicine approach. This is a comprehensive strategy, integrating best medical practice, bioinformatics and molecular biology with economy, artificial intelligence and machine learning. Circular Medicine is the resilient framework linking all these topics with circular economy methods. Innovative possibilities of circular medicine are many: it is a comprehensive paradigm shift, countering a non-medicine based on simplistic algorithms with guidelines of insufficient effectiveness, reliability and generalizability, often passed off as innovative Artificial-Intelligence approaches. We launched in 2020 a still ongoing survey aimed at the dissemination of information and at a greater sensitivity of all our members and followers on these topics, striving to build circular medicine in the real-world. This position document is based on its preliminary results: 1. Studying and investigating the links among health, climate change, biodiversity, circular economy, robust Artificial Intelligence and Machine learning support are goals and needed practice suitable to be pursued by EMA and other medical and scientific associations. Circular economy will be fruitfully used in health facilities, including hospitals, with health professionals and life science researchers acting also in the role of influencers and opinion leaders. 2. The interventions based on epidemiology, environmental sciences, best practice in medicine, sustainable technologies and molecular biology, the pillars of a potential framework of circular medicine, need a robust bioinformatics and Artificial Intelligence support. 3. Academic curricula and health professionals CME courses should provide stronger digital knowledge, reliable procedures trainings and expertise along these lines. Daily routine of clinical observation and participatory dialogue are key elements for the progress toward a culture, practice and accomplishments of circular economy and medicine. 4. Molecular biology, still the most innovative field of medical and life science, has a role for strengthening the pathways of the circular economy, as a reliable and resilient basis of "circular medicine." 5. The lessons of COVID19, the ongoing battles for healthier lifestyles dealing with nutrition, exercise and against alcohol and cigarette smoking, and the concept of smart cities are some of the cornerstones of the proposed strategy for a real-world circular medicine. Debunking interventions against the misuse of scientific and medical are means for the development of circular economy and medicine. Effective roadmaps, guidelines and grids for recognizing and counteracting the overlap of bullying, imposter's fear, insufficient expertise and knowledge, fake assertions and evaluations are actively developed by EMA's ad-hoc workshops. AI knowledge and skills should be implemented within innovative molecular biology and medical best-practice academic-CME curricula.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Thioester Electrophiles as a New Class of SHAPE Probes

RNA is a multifunctional molecule capable of regulating gene expression, in large part because it can form a variety of RNA secondary and tertiary structures. The emergence of RNA viruses like SARS-CoV-2 emphasizes the need to accelerate our understanding of how viral RNA structure dictates its function. One approach to map RNA secondary structure, called Selective 2'-OH Acylation Analyzed by Primer Extension (SHAPE), utilizes select electrophiles that unbiasedly modifies the 2'-hydroxyl of riboses in unpaired nucleotides, forming adducts that are detected through a variety of sequencing methods. While SHAPE is widely utilized, most existing SHAPE reagents suffer from several drawbacks: 1) poor water solubility;2) limited commercial availability;and 3) they function optimally when freshly synthesized, requiring synthetic organic expertise. To overcome these obstacles, our goal is to develop a userfriendly SHAPE reagent kit that provides highly reactive, soluble SHAPE reagents capable of probing RNA structure in vitro as well as in vivo. We present our investigations on developing thioester electrophiles as a new class of SHAPE reagents. Our reagent is prepared by mixing two stable components to generate the reactive thioester electrophile in situ. We report our preliminary results in model systems and the scope to expand the library of our reagents.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Nonhuman Primate Model of Long Covid: Immune Insights of Glycometabolic Dysfunctions

Background: A major consequence of COVID-19 is long-term metabolic complications (metabolic PASC or Long COVID) following acute disease resolution leading to hyperglycemia, increased risk of diabetes or defects in glucose metabolism. However, the mechanisms underlying the links between COVID-19 and glycometabolic disruptions remain unclear. Method(s): 15 African green monkeys (AGM;Chlorocebus aethiops) were infected with SARS-CoV-2 (Wuhan stain) and divided into two groups: unvaccinated (n=10) and vaccinated (BNT162b2 (Pfizer) 4-days post infection;n=5). Subgenomic SARS-CoV-2 mRNA (sgRNA) reflecting active replication was quantified in nasal and pharyngeal swabs, and blood chemistry analysis was performed longitudinally up to 18 weeks post-infection. We quantified liver glycogen at necropsy using Periodic acid-Schiff staining. Finally, we longitudinally analyzed 96 plasma proteins using a proximity extension assay (Olink). STRING was used to identify enriched protein networks. Comparisons between the two groups over time were performed using PERMANOVA. Result(s): All animals had detectable sgRNA ( >3.64x106) at day 3, and only two were undetectable at week 5. Post-infection BNT162b2 vaccination partially inhibited the SARS-CoV-2 mediated disruption of glucose levels (P=0.001, Fig. 1A). Liver glycogen levels following necropsy correlated positively with blood glucose levels at week 12 (r=0.74, P =0.003). Histopathological analysis revealed no marked evidence of long-term inflammation or fibrosis of pancreatic islets. Using the plasma proteomic data, we identified a signature of 15 SARS-CoV-2-modulated plasma proteins coinciding with early onset hyperglycemia during acute infection (P=0.001, Fig. 1B). These proteins are enriched for biological processes linked to chemotaxis (FDR=1.38E-06), and viral protein interaction with cytokines (FDR=1.01E-12) (Fig. 1C). Of these, CCL25 and glial cell derived neurotrophic factor (GDNF) remained persistently elevated post-acute infection and correlated with blood glucose levels (r=0.57, P=0.0003;and r=0.64, P<0.0001, respectively, Fig. 1D). Conclusion(s): Our AGM model validates phenotypes of metabolic PASC and offers an opportunity to mechanistically study the manifestations of PASC. Our preliminary data suggest that vaccine-preventable early insults by metabolicregulating immune factors may contribute to long-term dysregulated liver and systemic glucose homeostasis during PASC. These immune factors warrant further investigation for their mechanistic links to PASC. (Figure Presented).

Effectiveness and safety of elexacaftor/tezacaftor/ivacaftor therapy: An Italian center experience

Background: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA), a triple CFTR modulator combination, has proved to be highly effective in Phe508del homozygous and Phe508del/minimal function compound heterozygous people with cystic fibrosis (PwCF).We report preliminary data on the realworld effectiveness and safety of ELX/TEZ/IVA after 6 months of treatment. Method(s):We collected prospective data on PwCF who started ELX/TEZ/IVA and evaluated changes in pulmonary function (spirometry and lung clearance index [LCI]), nutritional status (body mass index [BMI]), sweat chloride, and rate of hospitalization from baseline to 6 months of treatment. Result(s): Between August 2021 and October 2021, ELX/TEZ/IVAwas started in 24 PwCF (12 female,10 Phe508del-homozygous, median age 20.5 (range 13-37), all with pancreatic insufficiency). After 6 months of treatment, all respiratory function indicators improved (median change: +16% percentage predicted forced expiratory volume in 1 second, +12% percentage predicted forced vital capacity, +23% percentage predicted forced expiratory flow at 25/75%, -2 lung clearance index). Improvement was also observed in BMI (+0.41 z-score) and sweat chloride concentrations (-54 mMol/L, 6 PwCF had Cl concentrations within the limit of normality) (Table 1). Over a 6-month period, only one hospitalization due to pulmonary exacerbations was observed, compared with 22 hospitalizations observed in the 6 months before starting ELX/TEZ/IVA (rate per 100 patient-months 15.3 vs 0.7, rate ratio 0.05, 95% CI, 0.01-0.29). Treatment was well tolerated, with only mild and transient adverse events consisting of headache (n = 4), cutaneous rash (n = 2), and mild hemoptysis (n = 2). One PwCF had intestinal subocclusion and required hospitalization. One patient had liver function test elevation after 6 months of therapy during an Changes in clinical variables and sweat test results from baseline through 6 months in patients treated with elexacaftor, tezacaftor and ivacaftor. Data are medians (interquartile ranges). Baseline vs 6 months compared usingWilcoxon signed-rank test. ppFEV1, percentage predicted forced expiratory volume in 1 second;ppFVC, percentage predicted forced vital capacity;ppFEV25/75, percentage predicted forced expiratory flow at 25/75%;LCI, lung clearance index;BMI, body mass index;Cl, chloride. (Table Presented) episode of SARS-COV2 infection, which required adjustment of the dose administered. Conclusion(s): Our data confirm that ELX/TEZ/IVA treatment is safe, well tolerated, and effective in PwCF. ELX/TEZ/IVA improved pulmonary function and nutritional status and remarkably reduced hospitalization rate. Our data indicate that introduction of ELX/TEZ/IVA in CF care will radically change the natural history of and management approach to the disease.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

SARS-CoV-2 VIRAL LOAD CHANGE IN A RANDOMIZED TRIAL ON THREE DIFFERENT EARLY THERAPIES

Background: SARS-CoV-2 Omicron sublineages exhibit evolving escape to in vitro neutralization by monoclonal antibodies (mAbs), with an unclear impact on in vivo treatment response. Our aim is to assess the impact of SARS-Cov-2 variants on the decline of viral load (VL) after treatment with 3 different drugs approved in EU for the early treatment of patients with mild-moderate COVID-19. Method(s): Post-hoc analysis from MONET (EudraCT: 2021-004188-28), phase 4 open-label RCT to assess efficacy of 500 mg intravenous sotrovimab (SOT), 600 mg intramuscular tixagevimab/cilgavimab (TIX/CIL) and oral 5-days course of NMV/r 300/100 mg BID, in non-hospitalized high-risk patients (pts) with early COVID-19. Pts' features were analyzed as binary variables by Chi-squared test. SARS-Cov-2 VL in nasopharyngeal swabs was carried out at randomization (1d) and at day 7 (7d) by cycle threshold value (Ct). Variant sequencing was performed at 1d. Ct variation was assessed by mixed effect log-linear model including random intercept at pts' level, log of Ct as independent variable, time, arm, viral variant as dependent variables, and interaction between time and arm. Multiple comparisons were adjusted by Bonferroni. Result(s): Among the 320 pts included between 4 Mar and 16 Nov, 2022, 108 (33.75%) received NMV/r, 103 (32.19%) TIX/CIL, and 109 (34.06%) SOT. Main characteristics were balanced across arms. Most of the pts were infected either with BA.2 (N=194;60.63%) or BA.4/BA.5 (N=100;31.25%) (Fig1A). VL at 1d was similar across the arms. In contrast, mean 7d VL was significantly lower in pts receiving NMV/r than in those receiving TIX/ CIL or SOT (P< 0.001) No significant VL variation was observed between the mAb arms (Fig1B). The analysis of the impact of viral variants suggests that while VL was significantly affected by variants (P=0.034), the superior effect of NMV/r over mAbs was homogeneous across all variant groups (P=0.290 for interaction) (Fig1C). Conclusion(s): Our study provides for the first time strong in vivo evidence that, when used against Omicron lineages, NMV/r exerts a stronger antiviral effect than mAbs. These results confirm previous in vitro evidence suggesting that mAbs may not retain neutralizing activity against all Omicron sublineages and provide preliminary information on how to use VL variation as a surrogate marker of efficacy. Further studies are needed to investigate whether the superior virologic activity of NMV/r over mAbs is confirmed for newly emerging variants, including BQ.1.1 or XBB.

Surfactant Protein B Reduces Respiratory Viral Infectivity in Human Lungs

Purpose of Study: COVID pneumonia caused by SARS-CoV-2 can result in a depletion of surfactant & lung injury, which resembles neonatal respiratory distress syndrome. Exogenous surfactant has shown promise as a therapeutic option in intubated hospitalized patients. Our preliminary data in human lung organoids (LOs) with a deficiency of surfactant protein B (SP-B) showed an increased viral load compared to normal LOs. Single cell RNA sequencing (scRNAseq) revealed that SP-B-deficient cells showed increased viral entry genes (ACE2 receptor) & dysregulated inflammatory markers emanating from the lung cells themselves. Our objective was to determine: (1) cell-specific transcriptional differences between normal & SP-B deficient human lung cells after infection with SARS-CoV-2 and (2) a therapeutic role of SP-B protein & surfactant in COVID-19 pneumonia. Methods Used: We used normal and SP-B mutant (homozygous, frameshift, loss of function mutation p.Pro133GlnfsTer95, previously known as 121ins2) human induced pluripotent stem cells (hiPSC) and differentiated them into 3D proximal lung organoids. The organoids were infected with the delta variant of SARS-CoV-2 for 24 hours at an MOI of 1. Infected and uninfected organoids were fixed in trizol in triplicate and underwent processing for bulk RNA sequencing. We tested for differentially expressed genes using the program DEseq. We also plated normal iPSC derived lung organoids as a monolayer and pre-treated them with 1mg/ml of Poractant alfa or 5 uM of recombinant SP-B protein. The delta strain of SARS-CoV-2 was added to the 96 wells at an MOI of 0.1 for one hour with shaking, then an overlay with DMEM/CMC/FBS was added and left on for 23 hours. The plate was fixed and stained for nucleocapsid (NC) protein. Summary of Results: Bioinformatic analysis of the bulk RNA sequencing data showed an increase in the multiple cytokines and chemokines in the SP-B mutant LOs compared to control. We also saw differential gene expression patterns in the SP-B mutant LOs including a reduction in SFTPC, FOXA2, and NKX2-1 and an increase in IL1A, VEGFA, PPARG and SMAD3. In the exogenous surfactant experiments, there was a decrease in total expression of viral NC in the Poractant alfa & rSP-B-treated cells compared to SARS-CoV-2 infection alone (p<0.001). Conclusion(s): Surfactant modulates the viral load of SARS-CoV-2 infection in the human lung. Deficiency in SP-B results in the dysregulation of the lung epithelial inflammatory signaling pathways resulting in worsening infections.

National assessment of school resources in cystic fibrosis care centers

Background: Assessment of the prevalence and correlates of educational risk and school support needs of children with cystic fibrosis (CF) is limited. Educational support for people with CF has become even more pressing with the onset of COVID-19 and the dramatic changes seen in the education system nationally. Method(s): A cross-sectional needs assessment survey for pediatric and adult CF center care team members across the United States was distributed to assess student and family school needs, resources, services offered, and current processes for identification of concerns and intervention. Care teams were asked to complete the survey as a group or specify respondents who routinely provide school support. Result(s): The survey was sent to 3684 individuals within the CF care center network, on April 1, 2022, with a closure date of April 22, 2022. Preliminary results at time of this submission include 56 survey responses, completed primarily by social workers (40%) and physicians (23%), representing approximately 20% of all centers. Thirty-eight percent of respondents reported that their center administered a screening tool to assess general school functioning routinely or as needed. Specific school topics most widely assessed included need for CF care (treatments and medications) to occur at school (73%), concerns about emotional and behavioral functioning in the school setting (70%), CF daily care burden affecting school attendance and performance (63%), and CF-specific needs in university settings (63%). According to the care team report, families most often asked for help with school accommodations related to ability to carry enzymes (74%), carrying awater bottle (50%), additional bathroom passes (43%), and ability to step out of the classroom as needed for gastrointestinal problems (50%). Nurses, program coordinators, and social workers are the team members addressing school needs most often (55%, 42%, and 90%, respectively). Sixty-two percent of respondents reported having access to a hospital-based teacher for education support during inpatient stays, 10% had access to school services or educational support, and 5% had access to someone with a background or training in education or teaching (other than hospital-based teacher) for ambulatory care. Upon closure of the survey, the above data will be updated, and more complete identification of current resources and future needs will be described at the 2022 North American Cystic Fibrosis Conference. Conclusion(s): This survey will be the most comprehensive assessment to date of ongoing school services at CF centers nationally. Results will be used to identify specific areas of need to guide development of a roadmap addressing proactive monitoring of school functioning and resources in the CF care modelCopyright © 2022, European Cystic Fibrosis Society. All rights reserved

Comparing artificial intelligence based diagnosis with expert results in SARS-COV-2 RT-qPCR

Objectives: Reverse transcription and real-time polymerase chain reaction (RT-qPCR) based on the SARS-CoV-2 viral RNA demonstration is the gold standard in diagnosis. Data files obtained from PCR devices should be analysed by a specialist physician and results should be transferred to Laboratory Information Management System (LIMS). CAtenA Smart PCR (Ventura, Ankara, Turkiye) program is a local bioinformatics software that assess PCR data files with artificial intelligence, submits to expert approval and transfers the approved results to LIMS. The aim of this study is to investigate its accuracy and matching success rate with expert analysis. Method(s): A total of 9400 RT-qPCR test results studied in Ankara Provincial Health Directorate Public Health Molecular Diagnosis Laboratory were compared with respect to expert evaluation and CAtenA results. Result(s): It was determined that the preliminary evaluation results of the CAtenA matched 86% of the negative and 90% of the positive results provided by expert analysis. 987 tests which CAtenA determined as inconclusive and suggested repeating PCR were found either negative or positive by expert analysis. A significant difference between positive and negative matching success rates and artificial intelligence (AI) based software overall accuracy was found and associated with the missed tests of the AI. Conclusion(s): As a result, it was suggested there is a low risk of confirming false positive results without expert analysis and test repetitions would cause losing time along with extra test costs. It was agreed that the PCR analysis used in CAtenA should be improved particularly in terms of test repetitions.Copyright © 2023 by Prusa Medical Publishing.