TREATMENT OF SHIZOPHRENIC PATIENTS AND rTMS

Introduction: Schizophrenia (SCH) is a heterogeneous syndrome characterized by positive and negative symptoms. Despite appropriate medication, about 1/4 of patients suffer for refractory positive and/or negative symptoms, which are associated with functional handicap, increase of duration and of the number of hospitalizations. Numerous studies have suggested that the pathophysiology of auditory hallucinations (AH) is related to a hyper activity of the left temporoparietal cortex (TPC). On the other hand, negative symptoms are associated with a prefrontal hypoactivity and the efficiency of pharmacological treatments is frequently partial. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation tool with excellent tolerability and safety. Given its hypothesized mechanisms of action and the clinical beneficial effects obtained in several types of pathology (Aleman et al. 2007), the efficacy of rTMS has been investigated for drug-resistant SCH symptoms. Objective: Our objective is to expose the knowledge concerning the rTMS use in the treatment of these symptoms and to purpose a critical analysis of these data. Method: a systematic review of the literature has been conducted using NIH Pubmed. The following search terms were used: TMS - rTMS - Schizophrenia - negative symptoms - hallucinations. Results: Concerning the treatment of AH, 16 publications and 4 meta analyses were selected. For the negative symptoms, we retained 16 studies and 3 meta analyses. The most extensively investigated application for rTMS in SCH is the use of low-frequency stimulation to the left TPC with the aim to improve AH symptomatology. When compared to sham, this type of acute course of rTMS has been proven to induce a substantial and significant reduction in AH. But this effect does not seem long-lasting and maintenance protocols must be developed. Concerning negative symptoms, the results are less solid but we find some works which demonstrate an improvement of these symptoms while various stimulation parameters were used. Recently, new parameters of stimulation in particular the theta burst stimulation have permitted us to obtain larger effects with longer duration. The interest of these new parameters will be discussed here. Conclusion: Overall, rTMS studies have demonstrated some promise in the treatment of SCH. However, more research is required to enhance rTMS efficacy and increase its beneficial effect duration and to test new therapeutic strategies in this topic

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

Occupational, academic, and personal determinants of wellbeing and psychological distress in residents: results of a survey in Lyon, France

IntroductionThe mental health of residents is a growing significant concern, particularly with respect to hospital and university training conditions. Our goal was to assess the professional, academic, and psychological determinants of the mental health status of all residents of the academy of Lyon, France.Materials and methodsThe Health Barometer of Lyon Subdivision Residents (BASIL) is an initiative which consists in proposing a recurrent online survey to all residents in medicine, pharmacy, and dentistry, belonging to the Lyon subdivision. The first of these surveys was conducted from May to July 2022. Participants should complete a series of validated questionnaires, including the Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS), and the Kessler Psychological Distress Scale (K6), respectively, and ad-hoc questions assessing their global health and hospital and academic working conditions. A Directed Acyclic Graph (DAG) analysis was conducted prior to multivariable analyses, to explore the determinants associated with low wellbeing (WEMWBS <43) and high psychological distress (K6 ≥ 13).ResultsA total of 904 residents (response rate: 46.7%) participated in the survey. A low level of wellbeing was observed in 23% of participants, and was significantly associated to job strain (OR = 2.18; 95%CI = [1.32–3.60]), low social support (OR = 3.13; 95%CI = [2.05–4.78]) and the experience of very poor university teaching (OR = 2.51; 95%CI = [1.29–4.91]). A high level of psychological distress was identified for 13% of participants, and associated with low social support (OR = 2.41; 95%CI = [1.48–3.93]) and the experience of very poor university teaching (OR = 2.89, 95%CI = [1.16–7.21]).ConclusionHospital working conditions, social support, and the perception of teaching quality, were three major determinants of wellbeing and psychological distress among health profession residents. Demographic determinants, personal life and lifestyle habits were also associated. This supports a multilevel action in prevention programs aiming to enhance wellbeing and reduce mental distress in this specific population and local organizational specificities

Exploring reasons for non-vaccination against human papillomavirus in Italy

BACKGROUND: In Italy, free-of-charge HPV vaccination is offered to 11-year-old girls since 2007. The National Immunization Plan established the target coverage at a minimum of 70%; it should increase to 95% within 3-year time frame. In 2012, four year after the introduction of HPV vaccination, coverage was stable at 69%. We conducted a national cross-sectional study to explore barriers to vaccination in Italy. METHODS: Vaccination services selected, through the immunization registries, a sample of unvaccinated girls born in 1997 or 1998 and posted to their families a 23-items questionnaire inquiring barriers to vaccination, HPV knowledge, source of information on HPV, perception of risk of contracting HPV, advice from consulted health professionals on HPV vaccination. RESULTS: We analysed 1,738 questionnaires. Main barriers were fear of adverse events (reported by 80% of families), lack of trust in a new vaccine (76%), discordant information received by health professionals (65%) and scarce information on HPV vaccination (54%). Overall, 54% of families replied correctly to more than half of 10 questions exploring knowledge on HPV vaccination. Families with a high knowledge score were more likely to live in Northern and Central Italy, be Italian, have a high educational level, include a mother who attended cervical screening regularly and consult more information sources. Although paediatricians/general practitioners and gynaecologists were considered the most trusted source of information by 79% and 61% of respondents, they were consulted only by 49% and 31%. Among parents who discussed vaccination with a physician, 28% received discordant advices and 31% received the recommendation of accepting vaccination. CONCLUSIONS: Fear of adverse events, discordance of information and advices from physicians, and scarce information were the more commonly reported barriers to HPV vaccination. Health professionals played a key role as information providers, thus they must be better trained to provide clear notions. Training needs to include the development of communication skills; transparent discussion about the pros and cons of vaccination may reduce fear of adverse events and increase trust in vaccination. The creation of a public health network around vaccination would allow sharing information and attitudes on vaccinations, so that homogeneous messages could reach the target population. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0545-9) contains supplementary material, which is available to authorized users

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

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Effects of smoking status and MADRS retardation factor on response to low frequency repetitive transcranial magnetic stimulation for depression

International audienceAbstract Background Despite growing evidence supporting the clinical interest of repetitive transcranial magnetic stimulation (rTMS) in treatment-resistant depression (TRD), little is known regarding the effects of clinical and sociodemographic factors on the clinical outcome in patients. Methods We retrospectively investigated the effects of clinical (using the 3-factor model of the Montgomery-Åsberg depression rating scale [MADRS] encompassing dysphoria, retardation and vegetative symptoms) and sociodemographic characteristics of participants on clinical outcome in a sample of 54 TRD patients receiving low frequency rTMS (1 Hz, 360 pulses) applied over the right dorsolateral prefrontal cortex combined with sham venlafaxine. Results Responders ( n = 29) displayed lower retardation baseline scores (13.6 ± 2.9) than non-responders (15.6 ± 2.9; n = 25; P = 0.02). We also observed a significant difference between the numbers of ex-smokers in responders and non-responders groups; all ex-smokers ( n = 8) were responders to rTMS ( P = 0.005). Conclusion Low MADRS retardation factor and ex-smoker status is highly prevalent in responders to low frequency rTMS. Further studies are needed to investigate the predictive value of these factors

Personal determinants of participation restriction after stroke - a systematic review of observational and qualitative studies

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