EMEA and Gene Therapy Medicinal Products Development in the European Union

The evaluation of quality, safety, and efficacy of medicinal products by the European Medicines Evaluation Agency (EMEA) via the centralized procedure is the only available regulatory procedure for obtaining marketing authorization for gene therapy (GT) medicinal products in the European Union. The responsibility for the authorization of clinical trials remains with the national competent authorities (NCA) acting in a harmonized framework from the scientific viewpoint. With the entry into force of a new directive on good clinical practice implementation in clinical trials as of 1 May 2004, procedural aspects will also be harmonized at EU level. Scientifically sound development of medicinal products is the key for the successful registration of dossiers and for contributing to the promotion and protection of public health. The objective of this paper is to introduce the EMEA regulatory processes and scientific activities relevant to GT medicinal products

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Relationship Between Scorpion Stings Events and Environmental Conditions in Mainland France

In the world, the impact of environmental conditions on the number of scorpion events was evaluated in North Africa,Middle East, and the Amazonian region but not in Europe. In mainland France, scorpion species described are Buthus occitanus (Amoreux, 1789), Belisarius xambeui (Simon, 1879) and 4 Euscorpiidae: Euscorpius concinnus (Koch, 1837), Euscorpius italicus (Herbst, 1800), Euscorpius tergestinus (Koch, 1837), and Tetratrichobothrius flavicaudis (De Geer, 1778). We aimed to describe the impact of environmental conduction on the number of scorpion events. For this, a retrospective multi-center study was conducted with data from the French poison control centers files about scorpion events between 1 January 2011 and 31 December 2020. During the study period, 975 incoming calls for scorpion events were recorded and 574 were related to scorpions native to mainland France and Corsica: B. occitanus (n = 86), Euscorpiidae species (n = 222), B. xambeui (n = 1), and undetermined species (n = 265). Cases were mostly reported along the Mediterranean coast, along rivers, and in cities with a trading port. The number of scorpion events was linked to the rivers' water level, rivers' flow, temperature, sunshine, and pluviometry (P < 0.05 for all variables). B. occitanus need warmest and driest environment than Euscorpiidae spp. A link between the severity of the envenoming and climatic condition or seasonality was not demonstrated

The AquiFR hydrometeorological modelling platform as a tool for improving groundwater resource monitoring over France: evaluation over a 60-year period

International audienceThe new AquiFR hydrometeorological modelling platform was developed to provide short-to-long-term forecasts for groundwater resource management in France. This study aims to describe and assess this new tool over a long period of 60 years. This platform gathers in a single numerical tool several hydrogeological models covering much of the French metropolitan area. A total of 11 aquifer systems are simulated through spatially distributed models using either the MARTHE (Modélisation d'Aquifères avec un mail-lage Rectangulaire, Transport et HydrodynamiquE; Modelling Aquifers with Rectangular cells, Transport and Hy-drodynamics) groundwater modelling software programme or the EauDyssée hydrogeological platform. A total of 23 karstic systems are simulated by a lumped reservoir approach using the EROS (Ensemble de Rivières Organisés en Sous-bassins; set of rivers organized in sub-basins) software programme. AquiFR computes the groundwater level, the groundwater-surface-water exchanges and the river flows. A simulation covering a 60-year period from 1958 to 2018 is achieved in order to evaluate the performance of this platform. The 8 km resolution SAFRAN (Système d'Analyse Fournissant des Renseignements Adaptés à la Nivologie) meteorological analysis provides the atmospheric variables needed by the SURFEX (SURFace EXternalisée) land surface model in order to compute surface runoff and groundwater recharge used by the hydrogeological models. The assessment is based on more than 600 piezometers and more than 300 gauging stations corresponding to simulated rivers Published by Copernicus Publications on behalf of the European Geosciences Union. 634 J.-P. Vergnes et al.: The AquiFR hydrometeorological modelling platform and outlets of karstic systems. For the simulated piezometric heads, 42 % and 60 % of the absolute biases are lower than 2 and 4 m respectively. The standardized piezometric level index (SPLI) was computed to assess the ability of AquiFR to identify extreme events such as groundwater floods or droughts in the long-term simulation over a set of piezome-ters used for groundwater resource management. A total of 56 % of the Nash-Sutcliffe efficiency (NSE; E f) coefficient calculations between the observed and simulated SPLI time series are greater than 0.5. The quality of the results makes it possible to consider using the platform for real-time monitoring and seasonal forecasts of groundwater resources as well as for climate change impact assessments

Poison control centres and alternative forms of communication: comparison of response rates between text message and telephone follow-up

INTRODUCTION: In recent years, the number of patients managed by poison control centres (PCCs) has increased without a proportional increase in the number of physicians. To improve efficiency without neglecting patient follow-up, some PCCs have begun using text messages. We evaluated the difference in response rates between text messaging and traditional telephone follow-up. MATERIALS AND METHODS: This retrospective, monocentric, non-randomised cohort study was conducted using data from calls made by the New Aquitaine PCC between February 27, 2019, and March 31, 2019. Patients were contacted up to three times by a phone call or short message service (SMS). RESULTS: For the analysis, 823 patients were included. At the end of follow-up, the response rates were similar in the phone call and SMS group (94 vs. 94%; p = 0.76) with median [interquartile range] response times of 0 min [0; 27 min] and 29 min [6; 120 min], respectively. The response rates did not differ in subgroups stratified according to sex, self-poisoning vs. relative response, age class, and solicitation during working hours vs. outside of working hours (all p > 0.5). Moreover, health practitioners required 2.4-fold more time to call than to send text messages (p < 0.001), and all practitioners were satisfied or very satisfied with text messaging implementation. CONCLUSION: Patients had good adherence to text messages. Text messages are easy to use, rapid, and allow the physician to easily prioritise follow-up without occupying the emergency line. Additionally, the costs of installation and maintenance are low for text message systems; these low costs facilitate the implementation of such services in various medical situations