Immune Response following BNT162b2 mRNA COVID-19 Vaccination in Pediatric Cancer Patients.

COVID-19 vaccinations are recommended for children with cancer but data on their vaccination response is scarce. This study assesses the antibody and T-cell response following a 2- or 3-dose vaccination with BNT162b2 mRNA COVID-19 vaccine in children (5-17 years) with cancer. For the antibody response, participants with a serum concentration of anti-SARS-CoV-2 spike 1 antibodies of >300 binding antibody units per milliliter were classified as good responders. For the T-cell response, categorization was based on spike S1 specific interferon-gamma release with good responders having >200 milli-international units per milliliter. The patients were categorized as being treated with chemo/immunotherapy for less than 6 weeks (Tx < 6 weeks) or more than 6 weeks (Tx > 6 weeks) before the first immunization event. In 46 patients given a 2-dose vaccination series, the percentage of good antibody and good T-cell responders was 39.3% and 73.7% in patients with Tx < 6 weeks and 94.4% and 100% in patients with Tx > 6 weeks, respectively. An additional 3rd vaccination in 16 patients with Tx < 6 weeks, increased the percentage of good antibody responders to 70% with no change in T-cell response. A 3-dose vaccination series effectively boosted antibody levels and is of value for patients undergoing active cancer treatment.

Lessons Learned from COVID19: Enhancing the Discipline of Communications in Pharmacovigilance

Introduction: Pharmacovigilance (PV) organizations are traditionally structured to address and comply with global regulations. However, PV organizations are well poised to contribute beyond legislation, by sharing insights across communities in a digestible, accessible way. Examining communication needs following the height of the COVID- 19 pandemic may elucidate opportunities for PV to play a more central role in public health, particularly in generating and disseminating timely, credible and accurate communications. The need for safety to play a larger role in combating vaccine hesitancy is well documented and is fundamental to building trust in patient populations. 1 While previous initiatives have focused on meeting the needs of legislation, research has indicated new approaches that incorporate a listening mechanism for public feedback are needed to provide tailored communications.1-2 PV organizations carry a responsibility to communicate directly to patients, due to their central positioning as a 'source of truth' for emerging safety information. The challenge is the level of uncertainty as a product's benefit/risk profile is characterized over time. Objective(s): We aim to identify safety-related communication needs across the healthcare ecosystem and propose an enhanced safety communication framework. Method(s): A three-part approach was taken to design a safety communications framework, addressing internal and external information needs. We performed a literature search to identify trends in PV innovation (2009-2022). Interviews were conducted with the Bei- Gene Global Patient Safety (GPS) organization to evaluate needs and communication opportunities within PV. Results were compared with lessons learned from the COVID-19 crisis. Result(s): Literature results demonstrated that PV innovation publications increased over the past decade, with a peak in 2015 and marked rise in 2021-2022, spanning numerous concepts. Publications relating to safety communications increased yearly since 2010, with over 300 articles published this year to date. Results from BeiGene interviews (N = 5) demonstrated the following opportunities: (1) Building awareness and understanding of PV externally, (2) Building networks of relevant stakeholders, (3) Demonstrating transparency with the public, (4) Generating accessible safety communications for patient populations by drawing on the discipline of communications in other industries. Qualitative research across 19 EU countries demonstrated critical gaps in addressing information needs throughout the pandemic relating to under-resourced public health services and lack of interoperative health IT systems.3 Conclusion(s): GPS has implemented a safety communications framework focused on internal and external communications, research and publications and ongoing intelligence monitoring. Its focus is to increase transparency, visibility and understanding of PV, with the aim to establish trust and credibility in healthcare communities.

Lessons Learned from COVID19: Enhancing the Discipline of Communications in Pharmacovigilance: An International Journal of Medical Toxicology and Drug Experience

Introduction: Pharmacovigilance (PV) organizations are traditionally structured to address and comply with global regulations. However, PV organizations are well poised to contribute beyond legislation, by sharing insights across communities in a digestible, accessible way. Examining communication needs following the height of the COVID19 pandemic may elucidate opportunities for PV to play a more central role in public health, particularly in generating and disseminating timely, credible and accurate communications. The need for safety to play a larger role in combating vaccine hesitancy is well documented and is fundamental to building trust in patient populations. 1 While previous initiatives have focused on meeting the needs of legislation, research has indicated new approaches that incorporate a listening mechanism for public feedback are needed to provide tailored communications.1-2 PV organizations carry a responsibility to communicate directly to patients, due to their central positioning as a 'source of truth' for emerging safety information. The challenge is the level of uncertainty as a product's benefit/risk profile is characterized over time. Objective: We aim to identify safety-related communication needs across the healthcare ecosystem and propose an enhanced safety communication framework. Methods: A three-part approach was taken to design a safety communications framework, addressing internal and external information needs. We performed a literature search to identify trends in PV innovation (2009-2022). Interviews were conducted with the BeiGene Global Patient Safety (GPS) organization to evaluate needs and communication opportunities within PV. Results were compared with lessons learned from the COVID-19 crisis. Results: Literature results demonstrated that PV innovation publications increased over the past decade, with a peak in 2015 and marked rise in 2021-2022, spanning numerous concepts. Publications relating to safety communications increased yearly since 2010, with over 300 articles published this year to date. Results from BeiGene interviews (N = 5) demonstrated the following opportunities: (1) Building awareness and understanding of PV externally, (2) Building networks of relevant stakeholders, (3) Demonstrating transparency with the public, (4) Generating accessible safety communications for patient populations by drawing on the discipline of communications in other industries. Qualitative research across 19 EU countries demonstrated critical gaps in addressing information needs throughout the pandemic relating to under-resourced public health services and lack of interoperative health IT systems.3 Conclusion: GPS has implemented a safety communications framework focused on internal and external communications, research and publications and ongoing intelligence monitoring. Its focus is to increase transparency, visibility and understanding of PV, with the aim to establish trust and credibility in healthcare communities.

PRE-EXPOSURE PROPHYLAXIS for SARS-COV-2 INFECTION with SUBCUTANEOUS CASIRIVIMAB/IMDEVIMAB in PATIENTS with IMMUNE MEDIATED INFLAMMATORY DISEASES

Background: Patients with immune-mediated infammatory diseases (IMID), particularly if treated with B-cell depleting therapies, show reduced humoral responses to SARS-CoV-2 vaccines and increased risk of severe COVID-19 (1,2). Since pre-exposure prophylaxis (PrEP) with monoclonal antibodies against SARS-CoV-2 proved effective in preventing infection and COVID-19 (3) in the general population, PrEP could be used for passive immunization of vaccine-refractory patients with IMIDs. Objectives: To evaluate the persistence of serum and salivary anti-SARS-CoV-2 IgG antibodies in vaccine-refractory patients with IMID after PrEP with casiriv-imab/imdevimab. Secondary outcomes were safety, SARS-CoV-2 infection, and adverse COVID-19 outcomes. Methods: We performed a longitudinal analysis on anti-SARS-CoV-2 IgG titers in IMID patients who received a PrEP with 1200 mg of subcutaneous casirivimab/imdevimab due to high infection risk, as they had not developed an adequate humoral response at least 21 days after three COVID-19 vaccinations (Table 1). Serum and salivary anti-SARS-CoV-2 Spike IgG were quantifed by ELISA (EUROIMMUN, Lübeck, Germany) before PrEP and after 1, 14, and 30 days. IgG levels are given as antibody ratios by dividing the optical density of the sample by that of the calibrator. A cutoff of ≥1.1 was considered positive. Safety as well as polymerase chain reaction (PCR)-confrmed SARS-CoV-2 infection and adverse COVID-19 outcomes (hospitalization, mechanical ventilation, death) after PrEP were recorded. Results: We obtained 92 serum and 75 saliva samples from 26 participants at four consecutive timepoints (Figure 1). Anti-SARS-CoV-2 IgG titers were observed in serum and saliva samples of all participants from day 1 and throughout 30 days after PrEP independently of diagnosis, therapy, total IgG, and peripheral CD19+ B-cells. Serum IgG increased rapidly at day 1 and plateaued from day 14 to 30 (Figure 1A), reaching similar levels as seen in healthy subjects after full vaccination (1), while saliva IgG increased steadily from administration up to day 14 and plateaued at day 30 (Figure 1B). No side effects were reported. Five patients (19.2%) had a close contact with a SARS-CoV-2-infected person, after which all but one remained asymptomatic and with a negative PCR test. The patient who tested positive developed mild COVID-19 with fever and cough. Conclusion: SARS-CoV-2 PrEP induces stable serum and salivary antibody levels in IMID patients who did not respond to COVID-19 vaccination, regardless of pre-existing clinical and serological features. In IMID, PrEP with casiriv-imab/imdevimab is safe and has the potential to prevent infection and severe COVID-19.

Living conditions of people with diabetes: A scoping review on the impact of the COVID-19 pandemic in Germany

The present study gives an overview on the effects caused by the ongoing COVID-19 pandemic on the living and care situation of people with diabetes in Germany. For this purpose, a systematic search was conducted using the scoping review methodology. On the one hand, a systematic literature search was accomplished in scientific databases for empirical studies and in other search areas for other non-empirical publications. On the other hand, routinely collected electronic health data (routine data;e. g., health insurers administrative data, data from patient registers, medical billing, and drug care data from contractual physicians) were requested from health insurance companies, patient registries or other institutions to gain insight into the care situation of people with diabetes. The literature search identified a total of 53 publications (12 empirical studies and 41 other publications) which were included in the data extraction. Additionally, the methodological quality of the empirical studies was assessed. Due to the small number of empirical studies and their low methodological quality, the evidence gaps regarding the impact of the COVID-19 pandemic on care of people with diabetes are large. However, the empirical studies provide little evidence that the pandemic had a negative impact on the use of diabetes-specific services. The studies show fewer new and reenrolments in disease management programs for diabetes;fewer changes in prescriptions of blood glucose-lowering drugs;fewer diabetes diagnoses and a higher rate of diabetic ketoacidosis in children and adolescents. Additionally, the COVID-19 pandemic has encouraged the use of digital tools for the care of people with diabetes. The search for routine data remained without results. In summary, very limited reliable data on the effects of the COVID-19 pandemic on the care of people with diabetes in Germany was available.

Employment-at-Will in the United States and the Challenges of Remote Work in the Time of COVID-19

How should employers and employees negotiate the strange and unexpected issues that COVID-19 has forced us to confront in the past two years? Remote work, in particular, has dramatically changed the dynamic of many people's jobs, often altering the tasks and boundaries of employment, blurring the lines between work and home, public and private. U.S. employment law, and particularly the powerful employment-at-will doctrine, sets a clear standard but can sometimes be a blunt instrument. Is there any nuance to be found, or to be desired, from employers in these unprecedented times of COVID-19? We will discuss the doctrine of employment-at-will, the standard it creates for American employment, and the various exceptions to it that have arisen over the past several decades. We will then examine a couple of hypothetical workplace scenarios that could arise in a work-from-home environment, discuss how current law would address them, and whether the letter of the law is the best source of guidance in these matters. We will further discuss the challenges faced by many companies as they attempt to deal with these abrupt changes to their working environments. What are the effects, if any, on long-standing employment traditions and practices? What are the legal issues that may arise from them?

First interim analysis from the observational hempowr study evaluating effectiveness and safety of real-world treatment with damoctocog alfa pegol in previously treated patients with hemophilia a

Background : Damoctocog alfa pegol (BAY 94-9027) is an extended-half-life PEGylated recombinant factor VIII product, approved for use in previously-treated patients (PTPs) aged ≥12 years with hemophilia A. Aims : HEM-POWR (NCT03932201) is a multicenter, noninterventional, open-label, prospective phase IV trial investigating routine clinical use of damoctocog alfa pegol. Planned enrollment is ≥200 PTPs with mild, moderate, or severe hemophilia A. The 6-month interim safety analysis is presented. Methods : Eligible patients include all PTPs receiving damoctocog alfa pegol on-demand or as prophylaxis, according to local label who provided informed consent. Primary outcomes include total bleeding events and annualized bleeding rate. Secondary outcomes include long-term safety, joint health, and patient-reported outcomes. Analyses will be exploratory, stratified by prophylaxis regimen and hemophilia severity. Ethical approval was obtained for all sites. Results : At data cut-off (21 October), 39 PTPs were enrolled;38 patients comprised the safety analysis set (one patient withdrew consent), including 8 mild/moderate patients (Table 1). Most patients ( n = 32) had received damoctocog alfa pegol within 12 months of baseline for variable time periods (mean [SD]=354.6 [614.02] days). Median (Q1;Q3) dose was 3000 (2000;3650) IU/infusion;the most common dosing regimen being twice-weekly prophylaxis (44%). 26/32 patients provided information about Factor VIII treatment within 12 months prior to initiation of damoctocog alfa pegol. In this group, the most common dosing frequency was three times weekly (data available for 24 patients). A group of six damoctocog alfa pegol-naïve patients had a comparatively worse bleeding history (Table 2). There were no study-drug-related treatment-emergent adverse events, nor inhibitor development. Two patients discontinued. Remote follow-up visits were made due to Covid-19;initial visits may now be conducted remotely. Conclusions : This first interim analysis of the HEM-POWR study provides real-world evidence that damoctocog alfa pegol is welltolerated in routine clinical use in patients with mild, moderate, or severe disease.

The impact of COVID-19 on surgical activity

Aim This study aims to examine the impact of COVID-19 on surgical activity in a Model 3 Hospital. Methods A retrospective, observational study assessing data collected over a 3-month period (February to April) in 2019 and 2020. Results There was an overall reduction in surgical activity between 2019 and 2020. This impact was felt most acutely in the month of April where elective theatre and endoscopy procedures fell from 131 to 9 (93%) and 399 to 102 (74%) respectively. The number of emergency department admissions reduced from 534 to 408 (24%) and the number requiring surgical intervention fell from 166 to 122 (27%). Attendance at surgical outpatients fell from 1,211 to 677 (44%) between the 2019 and 2020. In April, attendance reduced from 456 to 52 (86%). Discussion This study has quantified the reduction in surgical department activity in our Model 3 Hospital. This reduction in scheduled and non-scheduled care could be extrapolated nationally to inform service planning, which will become increasingly challenged unless action to address the service deficit is taken soon.

SARS-CoV-2-induced encephalopathy

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is caused by coronavirus disease 2019 (COVID-19), first appeared in December 2019 in Wuhan/China. It has rapidly spread to multiple countries and has become a global health problem. The effects of the respiratory syndrome on the CNS (Central Nervous System) are reported in low but increasing numbers. We report a case of SARS-CoV-2-induced encephalopathy with a biphasic clinical presentation only after a neurologically silent period. © 2020 Georg Thieme Verlag. All rights reserved.

ECMO as a bridging to recovery in a 19-year-old patient with e-cigarette / vaping-product associated lung injury (EVALI)

Introduction: E-cigarettes are becoming increasingly popular among the younger generation. An increasing number of e-cigarette or vaping-product associated lung injuries (EVALI) has been published with some severe and even lethal outcomes. We report an unusually severe case with veno-venous ECMO being used as a bridging to recovery. Case Report: A previously healthy 19- year-old male was admitted to a hospital with shortness of breath. He had been suffering from progressive dyspnoea for about four weeks. The patient had been a frequent user of e-cigarettes and hookahs. Treatment was begun with noninvasive ventilation and continued with endotracheal intubation after rapid deterioration. Since hypercarbic pulmonary failure persisted the patient was transferred to an academic referral hospital. After a futile conservative approach with prone positioning, veno-venous ECMO was initiated. Extensive tests for infectious diseases (including SARS-CoV-2) or autoimmune conditions were nega- tive and the diagnosis of EVALI was made after transbronchial biopsy. Steroids and azithromycin were administered, resulting in a slow improvement after three weeks. The patient was eventually weaned from ECMO and ventilation after tracheostomy. He was discharged to a rehab facility and is now almost asymptomatic. However, pulmonary function testing does still demonstrate a marked obstruction predominantly affecting the small airways. Conclusion: After exclusion of other causes, and given the appropriate case history, EVALI must be considered as a rare diagnosis for pulmonary failure. Since the time to recovery can be substantial, veno-venous ECMO might be a therapeutic option bridging the patient until pulmonary function improves. Early transfer to a specialised facility appears appropriate.