Effectiveness of COVID-19 Vaccination on Reduction of Hospitalizations and Deaths in Elderly Patients in Rio Grande do Norte, Brazil.

Since the COVID-19 pandemic emerged, vaccination has been the core strategy to mitigate the spread of SARS-CoV-2 in humans. This paper analyzes the impact of COVID-19 vaccination on hospitalizations and deaths in the state of Rio Grande do Norte, Brazil. We analyzed data from 23,516 hospitalized COVID-19 patients diagnosed between April 2020 and August 2021. We excluded the data from patients hospitalized through direct occupancy, unknown outcomes, and unconfirmed COVID-19 cases, resulting in data from 12,635 patients cross-referenced with the immunization status during hospitalization. Our results indicated that administering at least one dose of the immunizers was sufficient to significantly reduce the occurrence of moderate and severe COVID-19 cases among patients under 59 years. Considering the partially or fully immunized patients, the mean age is similar between the analyzed groups, despite the occurrence of comorbidities and higher than that observed among not immunized patients. Thus, immunized patients present lower Unified Score for Prioritization (USP) levels when diagnosed with COVID-19. Our data suggest that COVID-19 vaccination significantly reduced the hospitalization and death of elderly patients (60+ years) after administration of at least one dose. Comorbidities do not change the mean age of moderate/severe COVID-19 cases and the days required for the hospitalization of these patients.

Early anti-S antibody levels predict anti-SARS-CoV-2 neutralizing activity over 24 weeks in RA patients after SARS-CoV-2 mRNA vaccination

Objectives: Routine monitoring of vaccine-induced anti-S responses following mRNA based SARS-CoV-2 vaccination is not recommended routinely as uncertainties exist about the critical threshold of antibody levels that correlate to protection and the optimal timepoint for determination. In our study, anti-S antibody were analysed over 24 weeks following a standard two-dose regimen of mRNA based anti-SARS-CoV-2 vaccines and correlated to the development and persistence of neutralizing activity against SARSCoV- 2 in patients with rheumatoid arthritis (RA) on DMARD therapy compared to healthy controls (HC). Method(s): The RECOVER study was a prospective, controlled, monocentric study. Assessments were performed before vaccination, and at three, six, 12 and 24 weeks after the first vaccine dose. Result(s): In RA patients, anti-S responses developed slower and resulted in lower peak titers compared to HC. A potent neutralizing activity (NT50) as assessed by a SARS-CoV-2 pseudoneutralization assay was observed in 60.3 % of all 73 RA patients and in all 21 HC after 12 weeks. A significant correlation between peak anti-S levels two weeks after the second vaccine dose and the development of a persistent neutralizing activity against SARS-CoV-2 was observed at week 12 and week 24. The analysis of IgG, IgA, and IgM isotype responses to RBD, S1, S2, and N proteins revealed a delayed IgG response, while IgA and IgM responses were maintained, suggesting a delayed isotype switch in RA patients. Conclusion(s): Peak anti-S IgG levels two weeks after the second vaccine dose significantly predicted the development and persistence of a potent neutralizing activity against SARS-CoV-2 after 12 and 24 weeks. Our data suggest that the early determination of anti- S levels allows the timely identification of non- or poor-responding patients.

IMPROVING THE PROVISION OF GASTROENTEROLOGY TEACHING TO NON-SPECIALIST TRAINEES

Introduction As more specialists become dual accredited in internal medicine, non-gastroenterology specialists have greater exposure to gastroenterology patients over the course of their training, especially via the acute take. Simultaneously, the COVID pandemic has meant most regular local teaching has moved online with varying quality. This project aimed to evaluate 1) whether a standardised protocol can be used to successfully deliver large scale digital gastroenterology teaching that 2) is non-inferior when compared with traditional face to face teaching. Methods Teaching was delivered to internal medical trainees on the acute management of ulcerative colitis and chronic liver disease. Two sessions were delivered a year apart, initially regionally, and then nationally. This was delivered via Zoom, using a standardised protocol based on guidelines to ensure consistency, with live-polled multiple-choice questions to encourage interaction. Each session was followed by Q&A related to that topic. Feedback was taken after each session. Outcome measures analysed were: number in attendance, whether viewers would recommend this teaching to others, whether they thought it ran smoothly, and how they felt about it when compared with face-to-face teaching as measured on a Likert scale. Given the subjective nature of our hypotheses, we accept that these are surrogate markers. Results 171 trainees attended the initial regional teaching session and 469 the subsequent session. Following the first session, 98.9% of trainees would recommend the teaching to others, rising to 99.7% after the second session. 99% and 99.5% respectively agreed or strongly agreed with the statement the initial session ran smoothly, while 84.5% and 88.8% agreed or strongly agreed that digital teaching was as effective as face to face. The benefits of digital teaching were no travel (90%) ability to watch later (86%), whereas the downsides were loss of social interaction (60%) and harder to get study leave (39%). Conclusions Gastroenterology teaching for non-specialists can be delivered successfully at a large scale using a standardised protocol for digital teaching. The vast majority of trainees felt that digital sessions were as effective as face-to-face teaching with a lack of travel and flexibility on viewing time the main reported benefits.

Teleworking in the Public Administration: An Analysis Based on Spanish Civil Servants' Perspectives During the Pandemic

COVID-19 has inflicted unprecedented damage on the entire concept of work and has prompted a paradigm shift in workplace relations. Many work environments have faced a context in which on-site work has been restricted and telework has been the only viable option. In countries like Spain, the pandemic has forced the Public Administration to opt for this way of working in order to continue operating. Therefore, this study aims to determine the catalysts and blockers for Spanish civil servants wanting to telework. To achieve the study's objectives, descriptive statistics were obtained using the multiple linear regression technique, with a model building system known as backward stepwise. The identification of these catalysts and blockers will help to facilitate human resource management based on teleworking in the public sector. This study's findings could help to recommend possible actions to improve the employees' teleworking experience at the Spanish Administracion General del Estado. These actions include investing in equipment, providing training in information and communication technologies, and defining human resources policy to promote the work-life balance.

First-in-human phase I study of a novel oral Wee1 inhibitor (Debio 0123) in combination with carboplatin in patients with advanced solid tumours

Background: The Wee1 tyrosine kinase is activated upon DNA damage and regulates the G2-M cell cycle checkpoint. Inhibition of Wee1, in conjunction with additional genetic alterations and/or addition of a DNA damaging agent, results in mitotic catastrophe and apoptosis of cancer cells, being an attractive approach for treating cancer. Debio 0123 is a potent and highly specific WEE1 inhibitor with an IC50 in the low nanomolar range. Debio 0123 was demonstrated to inhibit phospho-CDC2 which translated into an increase in DNA damage and premature entry into mitosis (AACR 2019, abstract 4423). Debio 0123 combination with carboplatin (CbPt) was synergic in vitro. In vivo, Debio 0123 was demonstrated to increase antitumoral activity of cbPt in models where neither agent was active alone. Trial design: Methods This is a phase I, multi-center, open-label, dose escalation study of Debio 0123 as monotherapy (first cycle only) and in combination with CbPt, from cycle 2 in subjects with advanced solid tumors that recurred or progressed following prior platinum therapy. Primary objective: determination of the recommended phase II dose (RP2D) of Debio 0123 when administered in combination with CbPt using a modified Continual Reassessment Method (mCRM). Patients receive Debio 0123 orally once daily for the first 3 days of a 21 day-cycle as monotherapy during first cycle and in combination with CbPt in following cycles. Secondary objectives: includes determination of occurrence of dose-limiting toxicities (DLT) and characterization of the pharmacokinetics of Debio 0123 and its active metabolite, which are evaluated after single and repeated administration when administered alone or in combination with CbPt. Potential risk of QTc prolongation is evaluated by exposure-response modeling. Pharmacodynamics biomarkers including phospho-CDC2 are explored in pre- and post-treatment tumors and skin biopsies. Recruitment started in July 2019. Cohort 2 has been completed. Start of enrollment into cohort 3 is currently unknow due to COVID-19 but will begin as soon as possible. Clinical trial identification: NCT03968653. Legal entity responsible for the study: Debiopharm Interbational S.A. Funding: Debiopharm International S.A. Disclosure: V. Nicolas: Full/Part-time employment: Debiopharm AS. A. Vaslin: Full/Part-time employment: Debiopharm AS. K. Tobal: Full/Part-time employment: Debiopharm AS. D. Purcea: Full/Part-time employment: Debiopharm AS. S.F. van Haren: Full/Part-time employment: Debiopharm AS. L. Damstrup: Full/Part-time employment: Debiopharm International S.A. All other authors have declared no conflicts of interest.