Brand-Specific Enhanced Safety Surveillance Study of GSK’s Quadrivalent Seasonal Influenza Vaccine, Conducted During the COVID-19 Pandemic, in Belgium, Germany and Spain, for the 2020/21 Season

Infectious disease; Influenza; Vaccine safetyEnfermedad infecciosa; Gripe; Seguridad de las vacunasMalaltia infecciosa; Grip; Seguretat de les vacunesIntroduction Seasonal influenza poses a major public health burden worldwide. Influenza vaccines, updated yearly to match circulating strains based on World Health Organization (WHO) recommendations, are the cornerstone of prevention and require regular monitoring. The COVID-19 pandemic is expected to cause logistical, site access and medical staff constraints and could affect the safety profile of influenza vaccines. Methods Following European Medicines Agency guidance, an enhanced safety surveillance (ESS) study assessed the frequency and severity of predefined and other adverse events (AEs) occurring within 7 days of receiving GSK’s inactivated quadrivalent seasonal influenza vaccine (IIV4), in Belgium, Germany and Spain in 2020/21, using adverse drug reaction (ADR) cards. Results During the 2020/21 influenza season, 1054 participants vaccinated with GSK’s IIV4 were enrolled (all adults in Belgium and Germany, 30% adults/70% children in Spain); 96 eligible children received a second dose. Overall, 1042 participants completed the study. After doses 1 and 2, 98.9% and 100% of participants, respectively, returned their completed ADR card. After doses 1 and 2, 37.8% (398/1054) and 13.5% (13/96) of participants, respectively, reported at least one AE. The most frequently reported categories of AEs were “general disorders and administration site conditions” (e.g. injection site pain) and “nervous system disorders” (e.g. headache). There were no deaths or serious AEs deemed related to GSK’s IIV4. Conclusion This ESS study assessed AEs in near real time. The COVID-19 pandemic did not alter the safety profile of GSK’s IIV4. No safety signals were detected during the study, which confirms the excellent safety profile of GSK’s IIV4.GlaxoSmithKline Biologicals SA funded this study (study number 207750) and was involved in all stages of the study, including analysis of the data. GlaxoSmithKline Biologicals SA also took charge of all costs associated with the development and publication of this present manuscript, including the Journal’s Rapid Service Fee

Enhanced safety surveillance of GSK's quadrivalent seasonal influenza vaccine in Germany and Spain (2021/2022 season) using an electronic patient-reported outcome system for vaccine safety remote monitoring

Influenza; Safety; VaccinationGrip; Seguretat; VacunacióGripe; Seguridad; VacunaciónBackground Seasonal influenza epidemics are managed through vaccination each winter in the European Union, to prevent infections, complications, and deaths. As circulating virus strains vary unpredictably, vaccines are reformulated annually, and their safety monitored rapidly and continuously at the start of each season, following European Medicines Agency guidelines.Seasonal influenza epidemics are managed through vaccination each winter in the European Union, to prevent infections, complications, and deaths. As circulating virus strains vary unpredictably, vaccines are reformulated annually, and their safety monitored rapidly and continuously at the start of each season, following European Medicines Agency guidelines. Methods This enhanced safety surveillance study assessed pre-specified and other adverse events (AEs) occurring within 7 days of GSK's inactivated quadrivalent seasonal influenza vaccine (IIV4) in children and adults in Spain and Germany. As the study was conducted during the COVID-19 pandemic (2021/2022 season), data were collected electronically, using a web portal or call center. Results Safety was assessed in 737 participants (median age 49 and 9 years in Germany and Spain, respectively, 19.3% with a chronic medical condition). After Dose 1 and Dose 2, respectively, 332 (45.1%) and 5 (26.3%) participants reported at least one AE, primarily pre-specified AEs. The most common AEs after Dose 1 (adults and children) were injection site pain, swelling or erythema, headache, and fatigue. After Dose 2 (in children), the most common AEs were injection site pain, rhinorrhea, fatigue, and decreased appetite. No new or unexpected safety issues were identified. Conclusion This study supports and confirms the safety profile of GSK's IIV4 in all age groups with a vaccine indication. The new electronic safety reporting method (with response rates of 75.4% following Dose 1 and 100% following Dose 2) provides an alternative for future studies to reduce the burden on sites or in case site visits are not feasible.GlaxoSmithKline Biologicals SA is the funding source and was involved in all stages of the study. GlaxoSmithKline Biologicals SA also funded all costs associated with the development and the publishing of the present manuscript

Validity of clinical severity scores for respiratory syncytial virus: a systematic review

Background: Respiratory syncytial virus (RSV) is a widespread respiratory pathogen, and RSV-related acute lower respiratory tract infections are the most common cause of respiratory hospitalization in children <2 years of age. Over the last 2 decades, a number of severity scores have been proposed to quantify disease severity for RSV in children, yet there remains no overall consensus on the most clinically useful score. Methods: We conducted a systematic review of English-language publications in peer-reviewed journals published since January 2000 assessing the validity of severity scores for children (≤24 months of age) with RSV and/or bronchiolitis, and identified the most promising scores. For included articles, (1) validity data were extracted, (2) quality of reporting was assessed using the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis checklist (TRIPOD), and (3) quality was assessed using the Prediction Model Risk Of Bias Assessment Tool (PROBAST). To guide the assessment of the validity data, standardized cutoffs were employed, and an explicit definition of what we required to determine a score was sufficiently validated. Results: Our searches identified 8541 results, of which 1779 were excluded as duplicates. After title and abstract screening, 6670 references were excluded. Following full-text screening and snowballing, 32 articles, including 31 scores, were included. The most frequently assessed scores were the modified Tal score and the Wang Bronchiolitis Severity Score; none of the scores were found to be sufficiently validated according to our definition. The reporting and/or design of all the included studies was poor. The best validated score was the Bronchiolitis Score of Sant Joan de Déu, and a number of other promising scores were identified. Conclusions: No scores were found to be sufficiently validated. Further work is warranted to validate the existing scores, ideally in much larger datasets

An approach to apply automated acceptance testing for industrial robotic systems

Industrial robotic systems (IRS) are systems composed of industrial robots that automate industrial processes. They execute repetitive tasks with high accuracy, replacing or supporting dangerous jobs. Consequently, a low failure rate is crucial in IRS. However, to the best of our knowledge, there is a lack of automated software testing for industrial robots. In this paper, we describe a test strategy implementation to apply BDD to automate acceptance testing for IRS

I.C.E.: An Ultra-Cold Atom Source for Long-Baseline Interferometric Inertial Sensors in Reduced Gravity

The accuracy and precision of current atom-interferometric inertialsensors rival state-of-the-art conventional devices using artifact-based test masses . Atomic sensors are well suited for fundamental measurements of gravito-inertial fields. The sensitivity required to test gravitational theories can be achieved by extending the baseline of the interferometer. The I.C.E. (Interf\'erom\'etrie Coh\'erente pour l'Espace) interferometer aims to achieve long interrogation times in compact apparatus via reduced gravity. We have tested a cold-atom source during airplane parabolic flights. We show that this environment is compatible with free-fall interferometric measurements using up to 4 second interrogation time. We present the next-generation apparatus using degenerate gases for low release-velocity atomic sources in space-borne experiments

Results of the third Marine Ice Sheet Model Intercomparison Project (MISMIP+)

We present the result of the third Marine Ice Sheet Model Intercomparison Project, MISMIP+. MISMIP+ is intended to be a benchmark for ice-flow models which include fast sliding marine ice streams and floating ice shelves and in particular a treatment of viscous stress that is sufficient to model buttressing, where upstream ice flow is restrained by a downstream ice shelf. A set of idealized experiments first tests that models are able to maintain a steady state with the grounding line located on a retrograde slope due to buttressing and then explore scenarios where a reduction in that buttressing causes ice stream acceleration, thinning, and grounding line retreat. The majority of participating models passed the first test and then produced similar responses to the loss of buttressing. We find that the most important distinction between models in this particular type of simulation is in the treatment of sliding at the bed, with other distinctions - notably the difference between the simpler and more complete treatments of englacial stress but also the differences between numerical methods - taking a secondary role. © 2020 Wolters Kluwer Medknow Publications. All rights reserved

Results of the third Marine Ice Sheet Model Intercomparison Project (MISMIP+)

We present the result of the third Marine Ice Sheet Model Intercomparison Project, MISMIP+. MISMIP+ is intended to be a benchmark for ice-flow models which include fast sliding marine ice streams and floating ice shelves and in particular a treatment of viscous stress that is sufficient to model buttressing, where upstream ice flow is restrained by a downstream ice shelf. A set of idealized experiments first tests that models are able to maintain a steady state with the grounding line located on a retrograde slope due to buttressing and then explore scenarios where a reduction in that buttressing causes ice stream acceleration, thinning, and grounding line retreat. The majority of participating models passed the first test and then produced similar responses to the loss of buttressing. We find that the most important distinction between models in this particular type of simulation is in the treatment of sliding at the bed, with other distinctions – notably the difference between the simpler and more complete treatments of englacial stress but also the differences between numerical methods – taking a secondary role

Challenges in implementing yearly enhanced safety surveillance of influenza vaccination in Europe: lessons learned and future perspectives

Seasonal influenza vaccines are frequently reformulated, leading to specific challenges for continuous benefit/risk monitoring. In 2014, the European Medicines Agency started requiring annual enhanced safety surveillance (ESS). This article provides a perspective on ESS studies conducted ever since and aims to map existing initiatives used to monitor adverse events following influenza immunization. Of 11 ESS studies, reporting surveillance data of at least five different vaccine brands during four seasons, all were able to rapidly capture vaccine-specific adverse events of interest reports. However, challenges have been identified during study implementation, including recruitment of sufficient participants, enrolling younger age groups, collecting data of vaccine batch numbers, comparing observed with expected rates and achieving adequate return of reported events. Harmonizing safety monitoring standards across countries, and bridging between routine pharmacovigilance and ESS, is likely to allow more comprehensive assessments of influenza vaccine safety, requiring close collaboration between regulators, public health, and manufacturers

Relation entre activité physique et risque de cancer su sein chez la femme à partir des données de la cohorte E3N

ORSAY-PARIS11-Bib. STAPS (914712103) / SudocSudocFranceF

Twin Peaks: A/H1N1 Pandemic Influenza Virus Infection and Vaccination in Norway, 2009-2010.

BACKGROUND:Vaccination campaigns against A/H1N1 2009 pandemic influenza virus (A/H1N1p) began in autumn 2009 in Europe, after the declaration of the pandemic at a global level. This study aimed to estimate the proportion of individuals vaccinated against A/H1N1p in Norway who were already infected (asymptomatically or symptomatically) by A/H1N1p before vaccination, using a mathematical model. METHODS:A dynamic, mechanistic, mathematical model of A/H1N1p transmission was developed for the Norwegian population. The model parameters were estimated by calibrating the model-projected number of symptomatic A/H1N1p cases to the number of laboratory-confirmed A/H1N1p cases reported to the surveillance system, accounting for potential under-reporting. It was assumed in the base case that the likelihood of vaccination was independent of infection/disease state. A sensitivity analysis explored the effects of four scenarios in which current or previous symptomatic A/H1N1p infection would influence the likelihood of being vaccinated. RESULTS:The number of model-projected symptomatic A/H1N1p cases by week during the epidemic, accounting for under-reporting and timing, closely matched that of the laboratory-confirmed A/H1N1p cases reported to the surveillance system. The model-projected incidence of symptomatic A/H1N1p infection was 27% overall, 55% in people <10 years old and 41% in people 10-20 years old. The model-projected percentage of individuals vaccinated against A/H1N1p who were already infected with A/H1N1p before being vaccinated was 56% overall, 62% in people <10 years old and 66% in people 10-20 years old. The results were sensitive to assumptions about the independence of vaccination and infection; however, even when current or previous symptomatic A/H1N1p infection was assumed to reduce the likelihood of vaccination, the estimated percentage of individuals who were infected before vaccination remained at least 32% in all age groups. CONCLUSION:This analysis suggests that over half the people vaccinated against A/H1N1p in Norway during the 2009 pandemic may already have been infected by A/H1N1p before being vaccinated