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Saint Denis, France

Theophile H.,Bordeaux University Hospital Center | Dutertre J.-P.,Laboratoires SERB | Gerardin M.,Nantes University Hospital Center | Valnet-Rabier M.-B.,Besancon University Hospital Center | And 6 more authors.
Therapie | Year: 2015

Objective. Assess the validity and reproducibility of the updated version of the French causality assessment method in conditions approaching real-life use. Methods. A random sample of 31 drug-event pairs from the French pharmacovigilance database was assessed by the consensual judgement of three experts (gold standard). Separately, a team from a pharmacovigilance centre (PhVC) and another from a pharmaceutical company assessed these pairs using the current method, then with the updated method. To test the inter- and intra-rater reproducibility, two seniors and two juniors from a PhVC and a pharmaceutical company assessed the pairs twice with the updated method. A weighted kappa coefficient was used to measure the agreement of the two causality assessment methods with the consensual expert judgement (validity) as well as the agreement of the updated causality assessment over time (intra-rater reproducibility) and between evaluators (inter-rater reproducibility). Results. Agreement between the current method and consensual expert judgement was fair for the PhVC team (weighted kappa [Kw] 0.33) and moderate for the pharmaceutical company team (Kw 0.41). For the updated method, agreement was better for both the PhVC (Kw 0.58) and the pharmaceutical company (Kw 0.52) teams. The inter- and intra-rater reproducibility of the updated method based on the intrinsic imputability was satisfactory overall (Kw 0.30-0.91). Discrepancies between evaluations from PhVC and pharmaceutical companies were observed with the updated method. Conclusion. The updated method performed better than the current one for drug causality assessment, suggesting that it should be used in routine pharmacovigilance. © 2015 Société Française de Pharmacologie et de Thérapeutique. Source


Relano-Gines A.,French National Center for Scientific Research | Gabelle A.,French National Center for Scientific Research | Gabelle A.,Montpellier University Hospital Center | Hamela C.,French National Center for Scientific Research | And 7 more authors.
PLoS Pathogens | Year: 2013

Prion diseases are irreversible progressive neurodegenerative diseases, leading to severe incapacity and death. They are characterized in the brain by prion amyloid deposits, vacuolisation, astrocytosis, neuronal degeneration, and by cognitive, behavioural and physical impairments. There is no treatment for these disorders and stem cell therapy therefore represents an interesting new approach. Gains could not only result from the cell transplantation, but also from the stimulation of endogenous neural stem cells (NSC) or by the combination of both approaches. However, the development of such strategies requires a detailed knowledge of the pathology, particularly concerning the status of the adult neurogenesis and endogenous NSC during the development of the disease. During the past decade, several studies have consistently shown that NSC reside in the adult mammalian central nervous system (CNS) and that adult neurogenesis occurs throughout the adulthood in the subventricular zone of the lateral ventricle or the Dentate Gyrus of the hippocampus. Adult NSC are believed to constitute a reservoir for neuronal replacement during normal cell turnover or after brain injury. However, the activation of this system does not fully compensate the neuronal loss that occurs during neurodegenerative diseases and could even contribute to the disease progression. We investigated here the status of these cells during the development of prion disorders. We were able to show that NSC accumulate and replicate prions. Importantly, this resulted in the alteration of their neuronal fate which then represents a new pathologic event that might underlie the rapid progression of the disease. © 2013 Relaño-Ginès et al. Source


Arimone Y.,Cellule Plan de Gestion de Risque | Bidault I.,ANSM | Dutertre J.-P.,Laboratoires SERB | Gerardin M.,Nantes University Hospital Center | And 7 more authors.
Therapie | Year: 2013

The Imputability Working Group (CRI) updated the French drug reaction causality assessment method. This tripartite group is made up of staff from the French network of regional pharmacovigilance centres, pharmaceutical companies, and the French National Agency for the Safety of Medicines and Health Products (ANSM). After reviewing the strengths and weaknesses of the previous method, several ideas for improvement were proposed: a better-worded and more discriminating scale for certain chronological and semiological criteria, a larger scale for the intrinsic score (increased from 5 to 7 levels), a new bibliographical scale to differentiate between expected and unexpected adverse drug reactions, and a new informativeness scale. © 2013 Société Française de Pharmacologie et de Thérapeutique. Source


Trenque T.,Reims University Teaching Hospitals | Trenque T.,University of Reims Champagne Ardenne | Maura G.,Reims University Teaching Hospitals | Herlem E.,Reims University Teaching Hospitals | And 5 more authors.
Drug Safety | Year: 2013

Background: Depressive disorders and use of antidepressants are associated with adverse effects on sexual function. In pharmacoepidemiological studies, sexual disorders are reported by more than 50 % of patients taking serotonin reuptake inhibitors (SRIs). Objective: The aim of this study was to determine the reporting rate of sexual disorders in association with SRIs, and to investigate the association between reported cases and the use of SRIs. Methods: All cases of adverse drug reactions (ADRs) involving sexual disorders, spontaneously reported to the French Pharmacovigilance Database from 1 January 1985 to December 2009, were reviewed. Cases of sexual disorders in SRI users were described. We calculated the rate of reported sexual disorders as a percentage of the total ADRs reported for each drug. The association between reported cases and the use of SRIs was assessed using reporting odds ratios (ROR) with 95 % confidence intervals (CIs). Results: A total of 11,863 ADRs in association with SRIs were collected, of which 98 (0.83 %) were spontaneous reports of sexual disorders. Subjects were, on average, 45.0 ± 10.6 years of age and mainly male. Sexual disorders were associated with the use of SRI antidepressants (ROR 4.47; 95 % CI 3.61-5.53), milnacipran (ROR 11.72; 95 % CI 5.79-23.72), fluvoxamine (ROR 6.91; 95 % CI 3.79-12.58), paroxetine (ROR 5.54; 95 % CI 3.92-7.83), venlafaxine (ROR 3.50; 95 % CI 1.93-6.36), fluoxetine (ROR 3.46; 95 % CI 2.26-5.29), citalopram (ROR 2.69; 95 % CI 1.28-5.67) and sertraline (ROR 2.49; 95 % CI 1.03-6.01). Conclusion: It is likely that there are instances of underreporting, particularly for ADRs that are embarrassing to talk about spontaneously. Despite the likely underreporting of this well-described adverse effect, this case/non-case study performed in a large national pharmacovigilance database confirms the existence of the risk of sexual disorders associated with SRIs, and is an example of the lack of sensitivity of spontaneous notification to measure ADRs. Minimization of antidepressant- induced sexual dysfunction could be an important factor to avoid unsuccessful treatment. Physicians should advise their patients on the possible sexual adverse effects. © 2013 Springer International Publishing Switzerland. Source


Lirsac P.N.,CELLforCURE | Blin O.,Marseille University Hospital Center | Magalon J.,Laboratoire Of Culture Et Therapie Cellulaire | Magalon J.,French Institute of Health and Medical Research | And 13 more authors.
Therapie | Year: 2015

Although the European Union merely followed the initiatives of the United States and Japan by introducing special regimes for orphan medicinal products, it has introduced a special status for a new category of biological medicinal products, advanced therapy medicinal products (ATMPs), adopting specific associated regulations. European Regulation (which constitutes the highest legal instrument in the hierarchy of European law texts) [EC] No. 1394/2007, published in 2007, uses this term to define somatic cell therapy medicinal products, tissue-engineered products, and gene therapy medicinal products, possibly combined with medical devices. The stated objective was two-fold: both to promote their industrialization and market access, while guaranteeing a high level of health protection for patients. Since publication of the regulation, few marketing authorizations have been granted in Europe, and these have not been accompanied by commercial success. However, certain recent studies show that this is a growing sector and that France remains the leading European nation in terms of clinical trials. This round table brought together a panel of representatives of French public and private protagonists from the advanced therapy sector. The discussions focused on the conditions to ensure the success of translational research and, more generally, the French advanced therapy sector. These enabled a number of obstacles to be identified, which once lifted, by means of recommendations, would facilitate the development and success of this sector. © 2015 Société Franc¸aise de Pharmacologie et de Thérapeutique. Source

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