Clinical and Prognostic Value of Immunogenetic Characteristics in Anti-LGI1 Encephalitis

OBJECTIVE: Antibodies against leucine-rich glioma-inactivated 1 (LGI1-Abs) characterize a limbic encephalitis (LE) strongly associated with HLA-DRB1*07:01, although some patients lack LGI1-Abs in CSF or do not carry this allele. Whether they represent a different subtype of disease or have different prognoses is unclear. METHODS: Retrospective analysis of clinical features, IgG isotypes, and outcome according to LGI1-Ab CSF positivity and DRB1*07:01 in a cohort of anti-LGI1 LE patients. RESULTS: Patients with LGI1-Abs detected in both CSF and serum (105/134, 78%) were compared with those who were CSF negative (29/134, 22%). Both groups had similar clinical features and serum levels, but CSF-positive patients had shorter diagnostic delay, more frequently hyponatremia, inflammatory CSF, and abnormal MRI (p 0.05). HLA and IgG isotypes were not associated with poor outcome (mRS >2 at last follow-up) in univariate analyses; CSF positivity was only identified as a poor outcome predictor in the multivariate analysis including the complete follow-up, whereas age and female sex also remained when just the first year was considered. CONCLUSIONS: LE without CSF LGI1-Abs is clinically indistinguishable and likely reflects just a lesser LGI1-Ab production. HLA association is sex and age biased and presents clinical particularities, suggesting subtle differences in the immune response. Long-term outcome depends mostly on demographic characteristics and the intensity of the intrathecal synthesis

Exploring venlafaxine pharmacokinetic variability with a phenotyping approach, a multicentric french-swiss study (MARVEL study).

It is well known that the standard doses of a given drug may not have equivalent effects in all patients. To date, the management of depression remains mainly empirical and often poorly evaluated. The development of a personalized medicine in psychiatry may reduce treatment failure, intolerance or resistance, and hence the burden and costs of mood depressive disorders. The Geneva Cocktail Phenotypic approach presents several advantages including the "in vivo" measure of different cytochromes and transporter P-gp activities, their simultaneous determination in a single test, avoiding the influence of variability over time on phenotyping results, the administration of low dose substrates, a limited sampling strategy with an analytical method developed on DBS analysis. The goal of this project is to explore the relationship between the activity of drug-metabolizing enzymes (DME), assessed by a phenotypic approach, and the concentrations of Venlafaxine (VLX) + O-demethyl-venlafaxine (ODV), the efficacy and tolerance of VLX. This study is a multicentre prospective non-randomized open trial. Eligible patients present a major depressive episode, MADRS over or equal to 20, treatment with VLX regardless of the dose during at least 4 weeks. The Phenotype Visit includes VLX and ODV concentration measurement. Following the oral absorption of low doses of omeprazole, midazolam, dextromethorphan, and fexofenadine, drug metabolizing enzymes activity is assessed by specific metabolite/probe concentration ratios from a sample taken 2 h after cocktail administration for CYP2C19, CYP3A4, CYP2D6; and by the determination of the limited area under the curve from the capillary blood samples taken 2-3 and 6 h after cocktail administration for CYP2C19 and P-gp. Two follow-up visits will take place between 25 and 40 days and 50-70 days after inclusion. They include assessment of efficacy, tolerance and observance. Eleven french centres are involved in recruitment, expected to be completed within approximately 2 years with 205 patients. Metabolic ratios are determined in Geneva, Switzerland. By showing an association between drug metabolism and VLX concentrations, efficacy and tolerance, there is a hope that testing drug metabolism pathways with a phenotypical approach would help physicians in selecting and dosing antidepressants. The MARVEL study will provide an important contribution to increasing the knowledge of VLX variability and in optimizing the use of methods of personalized therapy in psychiatric settings. ClinicalTrials.gov NCT02590185 (10/27/2015). This study is currently recruiting participants

Agreement between routine electronic hospital discharge and Scottish Stroke Care Audit (SSCA) data in identifying stroke in the Scottish population

Background In Scotland all non-obstetric, non-psychiatric acute inpatient and day case stays are recorded by an administrative hospital discharge database, the Scottish Morbidity Record (SMR01). The Scottish Stroke Care Audit (SSCA) collects data from all hospitals managing acute stroke in Scotland to support and improve quality of stroke care. The aim was to assess whether there were discrepancies between these data sources for admissions from 2010 to 2011. Methods Records were matched when admission dates from the two data sources were within two days of each other and if an International Classification of Diseases (ICD) code of I61, I63, I64, or G45 was in the primary or secondary diagnosis field on SMR01. We also carried out a linkage analysis followed by a case-note review within one hospital in Scotland. Results There were a total of 22 416 entries on SSCA and 22 200 entries on SMR01. The concordance between SSCA and SMR01 was 16 823. SSCA contained 5593 strokes that were not present in SMR01, whereas SMR01 contained 185 strokes that were not present in SSCA. In the case-note review the concordance was 531, with SSCA containing 157 strokes that were not present in SMR01 and SMR01 containing 32 strokes that were not present in SSCA. Conclusions When identifying strokes, hospital administrative discharge databases should be used with caution. Our results demonstrate that SSCA most accurately represents the number of strokes occurring in Scotland. This resource is useful for determining the provision of adequate patient care, stroke services and resources, and as a tool for research

Initiation d'un traitement anti-ostéoporotique après fracture de l'avant-bras ou de l'humérus chez la femme de plus de 50 ans : étude de cohorte rétrospective.

IntroductionMalgré leur efficacité prouvée en prévention secondaire, les taux d’initiation de traitements anti-ostéoporotiques (anti-OP) après fracture de fragilité (FF) ont été décrits comme faibles dans le monde entier. Cette étude visait à décrire l’initiation des traitements anti-OP dans un échantillon représentatif de femmes ayant été hospitalisées pour une fracture de l’humérus ou de l’avant-bras (FAB) entre 2009 et 2011 en France.Matériels/méthodesUne étude de cohorte rétrospective a été réalisée à partir des données de la base médico-administrative de l’Assurance maladie, l’échantillon généraliste des bénéficiaires, échantillon représentatif à l’échelle nationale de 600 000 personnes. Ont été incluses toutes les femmes âgées de 50 ans et plus ayant été hospitalisées pour une fracture de l’humérus ou une FAB entre 2009 et 2011 et n’étant pas sous traitement anti-OP dans les 12 mois précédents. Les traitements anti-OP initiés au cours de l’année suivant la fracture ont été analysés.RésultatsEntre 2009 et 2011, 729 femmes ont été hospitalisées pour une fracture de l’humérus ou une FAB et 284 étaient sous traitement anti-OP au moment de la fracture. Parmi les 445 femmes sans traitement prévalent, 131 (29,4 %) ont initié un traitement de supplémentation (vitamine D et/ou calcium) et 42 (9,4 %) un traitement pharmacologique dans l’année suivant leur fracture. Ces derniers incluaient les bisphosphonates (n = 21), le ranélate de strontium (n = 14), un traitement hormonal substitutif (n = 4) ou le raloxifène (n = 3). Le délai médian d’initiation de traitement anti-OP était de 96 jours, avec un intervalle interquartile entre 49 et 184 jours ; 75 % des traitements initiés ont été prescrits par des médecins généralistes.ConclusionMalgré les recommandations de bonne pratique de 2006 et les nombreuses initiatives visant à promouvoir le traitement anti-OP post-fracture, le taux d’initiation de traitement chez les femmes ayant été hospitalisées pour une FF est resté faible en 2009–2011 en France

Caractéristiques des personnes alcoolo-dépendantes incarcérées en maison d'arrêt - Characteristics of alcohol-dependent male inmates

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