[Serious Adverse Drug Reaction and Their Preventability in the Elderly Over 65 Years]. / Les effets indésirables médicamenteux graves et leur évitabilité chez des sujets âgés de plus de 65 ans.

AIM: To describe the serious adverse drug reactions (ADR) in elderly subjects aged over 65 years and assess their preventability. METHODS: A retrospective study was conducted at the Regional Pharmacovigilance Center of Champagne-Ardenne (northeast of France) between January and May 2013. Patients aged over 65 years who presented a serious ADR notified to the Regional Pharmacovigilance Center were included in the study. RESULTS: Over the study period, 100 subjects were included in the study. The sex ratio was 0.96. Twenty seven percent of serious ADR were preventable. Off-label use accounted for 20% and non-compliance for 5%. Bleeding events were the most common serious ADR (36%). The drugs most frequently involved in serious ADR were antithrombotic agents (31.4%). CONCLUSION: More than a quarter of serious ADR were preventable. Off-label use and non-compliance are the main causes identified in the occurrence of preventable serious ADR.

[Not Available]. / Les effets indésirables médicamenteux graves et leur évitabilité chez des sujets âgés de plus de 65 ans.

AIM: To describe the serious adverse drug reactions (ADR) in elderly subjects aged over 65 years and assess their preventability. METHODS: A retrospective study was conducted at the Regional Pharmacovigilance Center of Champagne-Ardenne (northeast of France) between January and May 2013. Patients aged over 65 years who presented a serious ADR notified to the Regional Pharmacovigilance Center were included in the study. RESULTS: Over the study period, 100 subjects were included in the study. The sex ratio was 0.96. Twenty seven percent of serious ADR were preventable. Off-label use accounted for 20% and non-compliance for 5%. Bleeding events were the most common serious ADR (36%). The drugs most frequently involved in serious ADR were antithrombotic agents (31.4%). CONCLUSION: More than a quarter of serious ADR were preventable. Off-label use and non-compliance are the main causes identified in the occurrence of preventable serious ADR.

Notoriety bias in a database of spontaneous reports: the example of osteonecrosis of the jaw under bisphosphonate therapy in the French national pharmacovigilance database.

PURPOSE: The purpose of this study was to identify a notoriety bias in a database of spontaneous reports and its consequences on the calculation of the reporting odds ratio (ROR). METHODS: We used the case/noncase methodology to calculate the ROR for bisphosphonates and osteonecrosis of the jaw (ONJ) in the French national pharmacovigilance database (from 1985 to 2013). To evaluate notoriety bias, drug-related risk factors for ONJ [as specified in the summary of product characteristics (SPC) of bisphosphonates] were systematically scanned for notifications of reports of ONJ occurring under bisphosphonate therapy. When a risk factor was present, the ONJ was considered as not due to bisphosphonates, and a second ROR was calculated under the hypothesis of maximum bias. RESULTS: In total, 148 cases of ONJ were reported (143 with bisphosphonates and five without). The raw ROR was 3448 (95% confidence interval 1413-8417). After analysis of the reports, only 86 had no mention of a risk factor for ONJ. The ROR under the maximum bias hypothesis was 87 (95% confidence interval 63-121). Among ONJ where chemotherapy was being administered simultaneously to bisphosphonates, 27 reports did not consider the chemotherapy to be implicated, despite seven of these occurring in cases where ONJ was mentioned in the summary of product characteristics. CONCLUSIONS: The existence of a notoriety bias has an impact on measures of disproportionality. The detection of pharmacovigilance signals might be delayed. It is advisable to list all drugs being taken when an adverse drug reaction occurs, and not only those known to be associated with the observed reaction.

Class III phosphoinositide 3-kinase--Beclin1 complex mediates the amino acid-dependent regulation of autophagy in C2C12 myotubes.

Increased proteolysis contributes to muscle atrophy that prevails in many diseases. Elucidating the signalling pathways responsible for this activation is of obvious clinical importance. Autophagy is a ubiquitous degradation process, induced by amino acid starvation, that delivers cytoplasmic components to lysosomes. Starvation markedly stimulates autophagy in myotubes, and the present studies investigate the mechanisms of this regulation. In C(2)C(12) myotubes incubated with serum growth factors, amino acid starvation stimulated autophagic proteolysis independently of p38 and p42/p44 mitogen-activated protein kinases, but in a PI3K (phosphoinositide 3-kinase)-dependent manner. Starvation, however, did not alter activities of class I and class II PI3Ks, and was not sufficient to affect major signalling proteins downstream from class I PI3K (glycogen synthase kinase, Akt/protein kinase B and protein S6). In contrast, starvation increased class III PI3K activity in whole-myotube extracts. In fact, this increase was most pronounced for a population of class III PI3K that coimmunoprecipitated with Beclin1/Apg6 protein, a major determinant in the initiation of autophagy. Stimulation of proteolysis was reproduced by feeding myotubes with synthetic dipalmitoyl-PtdIns3 P, the class III PI3K product. Conversely, protein transfection of anti-class III PI3K inhibitory antibody into starved myotubes inverted the induction of proteolysis. Therefore, independently of class I PI3K/Akt, protein S6 and mitogen-activated protein kinase pathways, amino acid starvation stimulates proteolysis in myotubes by regulating class III PI3K-Beclin1 autophagic complexes.