Adverse consequences of low-dose methotrexate medication errors: data from French poison control and pharmacovigilance centers

International audienceObjectiveThe objectives of this study are to carefully describe the context of methotrexate medication errors, to details medical consequences and management approaches, and to determine the rate of fatal outcome.MethodsData on methotrexate medication errors were obtained from the French network of poison control and pharmacovigilance centres, which collected and documented reported drug-induced adverse effects. Cases were included if the intake was more than 2-fold the intended weekly dose or a weekly cumulative dose ≥ 30 mg and a follow-up of at least 4 days after the last dose. Data were analysed for demographics, treatment indication, prescribed dose, drug interactions, clinical complications and medical outcomes.ResultsSeventy four patients were included. The causes of methotrexate errors resulted from an erroneous prescription renewal (23.3%), incomprehensiveness of the weekly schedule by patients or at-home caregivers (56.2%) and administration of a wrong dose by a health care professional (20.5%). Of the 70 patients who took methotrexate daily, the mean daily dose received over the whole duration of the error was 9.6 ± 4.1 mg (range 2.5–22.5) with a mean duration of the error of 11.7 ± 12.2 days (range 2 to 90). Thirteen (18%) patients remained asymptomatic and 61 (82%) developed complications of which 46 (62.2%) were severe. Nine (14.8%) patients died within 11 to 45 days after the first dosing error. Compared to patients with no or mild symptoms, those with severe symptoms were more likely to be older (75.6 ± 10.8 vs. 69.5 ± 12.9 years) and to be exposed to a higher cumulative dose (94.8 ± 46.2 vs. 68.0 ± 45.7 mg).ConclusionsThis study confirms that dosing errors with methotrexate can be lethal and persisted despite several warnings from drug agencies. Further measures are awaited from the European Medicine Agency

CollEx-Persée.: CLA++ : Numérisation et signalement des publications d’artistes 2021 : vers une interopérabilité des bases documentairesProjet de recherche labellisé et cofinancé par

Projet en collaboration avec l'Unité de recherche Pratiques et théories de l’art contemporain (PTAC), EA 7472, Université Rennes 2, leService commun de documentation de l’université Rennes 2, le Fonds régional d’art contemporain de Bretagne (Frac), RennesSuite à la création de l’association Éditions Incertain Sens (IncS) en 2000, le projet de recherche sur les publications d’artistes est devenu un axe du laboratoire Arts : pratiques et poétiques (EA 3208) en 2007, aujourd’hui unité de recherche Pratiques et théories de l’art contemporain (PTAC, EA 7473). Dès 2003, le projet du Cabinet du livre d’artiste (CLA) a été inscrit au projet d’établissement de l’université Rennes 2. Il s’est installé dans le bâtiment Erève du campus Villejean en 2009, après avoir été accueilli pendant deux ans au Lycée Victor et Hélène Basch, situé dans le même quartier.Les publications d’artistes (livres, périodiques, brochures, tracts, etc.) constituent une pratique artistique, initiée aux quatre coins du monde dès le début des années 1960, qui utilise des techniques industrielles ou semi-industrielles, le plus souvent l’offset et l’impression numérique, comme supports et véhicules de projets artistiques. Il ne s’agit pourtant pas de reproductions imprimées d’œuvres, mais de publications considérées comme des œuvres à part entière, étant entendu que la notion traditionnelle d’œuvre ne peut s’y appliquer, ne serait-ce à cause de leur existence en centaines, voire en milliers d’exemplaires. Les analyses de Walter Benjamin ont insisté sur la transformation du concept même de l’art à l’époque de la reproductibilité des œuvres. Sous l’effet de la pratique par les artistes de publications ainsi entendues, l’art emprunte nombre d’éléments de la culture du livre et de la tradition de l’imprimerie, et il interroge, voire conteste, divers modes de comportements et d’usages propres aux formes et institutions artistiques convenues, en ouvrant de nouveaux espaces de la création et de la pratique de l’art.Le CLA constitue aujourd’hui un fonds documentaire d’environ 4.000 lots, pour la plupart des livres d’artistes. Conçu à l’origine comme une institution alternative de l’art, il constitue désormais des archives prisées par les chercheurs, et il est devenu un centre d’activités de recherches dédiées aux publications d’artistes (thèses de doctorats, colloques, collection éditoriale à visée scientifique etc.)

Feasibility and benefits of home initiation of subcutaneous apomorphine infusion for patients with Parkinson's disease: the APOKADO study

International audienceContinuous subcutaneous apomorphine infusion (CSAI) is used to treat patients with Parkinson's disease (PD) who are experiencing motor fluctuations. However, the need to initiate this treatment during a hospital stay may restrict patients' access to it. To assess the feasibility and benefits of initiating CSAI in the patient's own home. A French prospective multicenter longitudinal observational study (APOKADO) among patients with PD who required subcutaneous apomorphine, comparing in-hospital versus home initiation. Clinical status was assessed according to the Hoehn and Yahr score), the Unified Parkinson's Disease Rating Scale Part III, and the Montreal Cognitive Assessment. We assessed patients' quality of life with the 8-item Parkinson's Disease Questionnaire, rated the improvement in their clinical status on the 7-point Clinical Global Impression-Improvement scale, recorded adverse events, and ran a cost-benefit analysis. 145 patients with motor fluctuations were included in 29 centers (office and hospital). Of these, 106 (74%) were initiated onto CSAI at home, and 38 (26%) in hospital. At inclusion, the two groups were comparable for all demographic and PD characteristics. After 6 months, quality of life, adverse events and early dropout rates were similarly rare-across the two groups. Patients in the home group improved more quickly their quality of life and became more autonomous in managing the device than those in the hospital group, and their care costed less. This study shows that home (versus in-hospital) initiation of CSAI is feasible, improves patients' quality of life more quickly, with the same level of tolerance. It is also less expensive. This finding should make it easier for patients to access this treatment in the future

Exposure to ammonia solution due to substance use: a retrospective study from the French poison centres database (2009–2018)

Ammonia solution (ammonium hydroxide) is used to convert cocaine hydrochloride to freebase cocaine. Due to its causticity, unintentional exposure to ammonia in a substance use context can result in injury. The objective of this study was to describe the characteristics of unintentional oral and buccal ammonia solution exposure in a substance use context. A retrospective study was conducted using the French poison centres database over a 10-year period (2009–2018). A total of 1,546 files were extracted, and 263 substance users were included. There was a significant increase in the number of these exposures between 2009 and 2018. Unintentional ingestion of ammonia solution was linked to product decanting in 89 per cent of cases. Substance use prior to the exposure and a festive context, such as free parties or teknivals, were identified in 25 per cent and 21 per cent of cases, respectively. Patients received a hospital examination in 87 per cent of cases. The severity of intoxication in substance users was graded as moderate (33 per cent) or severe (15 per cent) using the Poisoning Severity Score. The increased number of ammonia solution cases reported was consistent with an increase in the number of crack users in Europe in the same period. Ammonia solution exposure can suggest the possibility of substance use disorders. In such cases, patients can be referred to receive appropriate treatment and support. This study had some limitations, such as the lack of available information due to the retrospective nature of the study and the non-standardized questions asked by the poison centre during the medical phone interviews. Oral and buccal ammonia solution exposure in known substance users in France increased between 2009 and 2018. These users were mostly young men. A festive context and decanting were frequent. Patients were mainly referred to emergency departments to receive clinical examination and care. The potential severity of oral or buccal ammonia solution exposure in substance users requires increased vigilance among all healthcare professionals involved in the management of these intoxication cases.</p

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

Molecular and clinical description of patients with GABA A receptor gene variants ( GABRA1 , GABRB2 , GABRB3 , GABRG2 ): a cohort study, review of literature, and genotype‐phenotype correlations

International audienceObjective: GABAA receptor subunit variants have recently been associated with neurodevelopmental disorders and/or epilepsy. The phenotype linked with each gene is becoming better known. Because of their common molecular structure and physiological role, it seemed interesting to describe a putative phenotype associated with GABAA -receptor-related disorders as a whole and seek possible genotype/phenotype correlations.Methods: We collected clinical, electrophysiological, therapeutic, and molecular data from patients affected with GABAA receptor subunit variants (GABRA1, GABRB2, GABRB3, GABRG2) through a national French collaboration using the EPIGENE network and compared them to the one already described in the literature.Results: We gathered the reported patients in 3 epileptic phenotypes: 15 patients with fever-related epilepsy (40%), 11 with early developmental epileptic encephalopathy (30%), 10 with generalized epilepsy spectrum (27%), and 1 patient without seizures (3%). We did not find a specific phenotype for any gene, but we showed that the location of variants on the transmembrane (TM) segment was associated with a more severe phenotype, irrespective of the GABAA receptor subunit gene, whereas N-terminal variants seemed to be related to milder phenotypes.Significance: GABAA receptor subunit variants are associated with highly variable phenotypes despite their molecular and physiological proximity. None of the genes described here was associated with a specific phenotype. On the other hand, it appears that the location of the variant on the protein may be a marker of severity. Variant location may have important weight in the development of targeted therapeutics