Centre Hospitalier du Rouvray

The efficacy and safety of esketamine nasal spray (ESK) were established in registration trials in patients with treatment-resistant depression (TRD). This French real-world study aimed to describe the treatment patterns, effectiveness, and safety of ESK in TRD patients over a 12-month follow-up. This study used secondary data from patient files of hospital-based psychiatrists and started during the first French patient early access to ESK. The response and remission rates with ESK were analyzed using the total score of the Montgomery-Åsberg Depression Rating Scale (MADRS). The time to first treatment response and work resumption were described (Kaplan-Meier method). Adverse events (AEs) were analyzed. Prior to ESK initiation, the 157 analyzed patients (age ≤ 65 years, 82.8%; female, 66.2%) had depression for 10.5 years (median, IQR, 4.2-21.2) and received a median of 6 (3-8) previous treatment lines. At ESK initiation, the mean ± SD total MADRS score was 32.1 ± 7.7. At that time, ESK was combined with antidepressants (93.6% of patients; SNRI, 65.0%; SSRI, 57.3%) and/or other potentiation strategy (63.1%; atypical antipsychotics, 36.3%; lithium, 25.6%; antiepileptics, 21.7%). During the 12-month follow-up, 125 patients (79.6%) discontinued ESK. The median duration of ESK treatment was 19.4 weeks (IQR, 4.4-40.1). At 1 month after ESK initiation, 40.2% of still treated patients met criteria for clinical response and 19.7% for remission (median time to response, 5.7 weeks; 95% CI (4.1-8.4)). 82.6% of active patients were on sick leave at ESK initiation; the work resumption rate was 24% (13%-40%) 12 weeks later. AEs were reported in 68.6% of patients, serious AEs in 17.2%, and AEs leading to ESK discontinuation in 14.6%. These real-world effectiveness and safety data were consistent with findings from previous clinical trials, describing the real-life clinical experience of patients receiving ESK and confirming that ESK has its place in therapy for the treatment of TRD.

IntroductionAttention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in children and adolescents. It is characterized by age-inappropriate inattention/impulsiveness and/or hyperactivity symptoms.However, emotional symptoms are frequent in patients with ADHD and may, in some cases, be responsible for a major part of the negative impact on functioning and outcome.It is now well established that a large number of children with ADHD and without any comorbid disorder exhibit symptoms of emotional lability.Recently , given the importance of the impact of emotional symtoms , several authors have argued that emotional intelligence affects health and is essential for success in academics as well as life in general and it is defined as the ability to perceive, appraise, and express emotions; the ability to access and/or generate feelings when they facilitate thought; and the ability to regulate emotions to promote emotional and intellectual growth.Objectives•Our research aimed to evaluate and compare the emotional and social functioning of two groups of children, with and without ADHD , aged 6 to 19 .Methods•One hundred twenty child (N=60 ADHD, N = 60 Control cases) were assessed with the BarOn Emotional Quotient Inventory: Youth Version (BarOn EQ-i:YV™), providing an estimate of their underlying emotional and social intelligence.•The BarOn EQ-i:YV is specifically designed to assess the coping skills, adaptability, and well-being of children and teenagers.•Children with ADHD and control cases were compared with each other.Results•The results showed that the Emotional Quotient (EQ) was significantly lower in the group of children with ADHD (p=0.01).•Also, our results showed that there are statistically significant differences in intrapersonal skills (p˂0.0010) Adaptability Scale(p=0.005) ; General Mood Scale (p=0.004) and positive impression (p = 0.001) of emotional intelligence between children with ADHD and control cases. Thus, the first group got lower scores than the second one in all aspects.Conclusions•ADHD is a disorder that affects the life quality of the person who suffers from it in the personal and social areas. Therefore, the emotional intelligence study in individuals with this diagnosis is important.•And considering the fact that abilities associated with emotional intelligence can be learned and improved, emotional intelligence can be thought as a target for therapy by individualized education for patients with ADHD who have inadequate abilities compared to the healthy population .Disclosure of InterestNone Declared

Depuis fin 2019, la fédération médicale inter-hospitalière des troubles du neuro-développement 276 ( fmih tnd 276) a développé des programmes de guidance parentale destinés aux familles d’enfants présentant un trouble du neurodéveloppement et demeurant en Normandie orientale (Eure et Seine-Maritime). Des formateurs à la guidance parentale ont été identifiés et formés pour développer quatre programmes de guidance : « Après l’annonce diagnostique », « Développer la communication de mon enfant », « Développer des axes liés à l’autonomie personnelle » et « Prendre en compte les particularités sensorielles de mon enfant dans sa vie quotidienne ». Des intervenants en guidance parentale ont été formés à ces programmes pour qu’ils puissent les mettre en place auprès des familles.

BackgroundAlzheimer disease (AD) is a common complex disorder with a high genetic component. Loss-of-function (LoF) SORL1 variants are one of the strongest AD genetic risk factors. Estimating their age-related penetrance is essential before putative use for genetic counseling or preventive trials. However, relative rarity and co-occurrence with the main AD risk factor, APOE-ε4, make such estimations difficult.MethodsWe proposed to estimate the age-related penetrance of SORL1-LoF variants through a survival framework by estimating the conditional instantaneous risk combining (i) a baseline for non-carriers of SORL1-LoF variants, stratified by APOE-ε4, derived from the Rotterdam study (N = 12,255), and (ii) an age-dependent proportional hazard effect for SORL1-LoF variants estimated from 27 extended pedigrees (including 307 relatives ≥ 40 years old, 45 of them having genotyping information) recruited from the French reference center for young Alzheimer patients. We embedded this model into an expectation-maximization algorithm to accommodate for missing genotypes. To correct for ascertainment bias, proband phenotypes were omitted. Then, we assessed if our penetrance curves were concordant with age distributions of APOE-ε4-stratified SORL1-LoF variant carriers detected among sequencing data of 13,007 cases and 10,182 controls from European and American case-control study consortia.ResultsSORL1-LoF variants penetrance curves reached 100% (95% confidence interval [99–100%]) by age 70 among APOE-ε4ε4 carriers only, compared with 56% [40–72%] and 37% [26–51%] in ε4 heterozygous carriers and ε4 non-carriers, respectively. These estimates were fully consistent with observed age distributions of SORL1-LoF variant carriers in case-control study data.ConclusionsWe conclude that SORL1-LoF variants should be interpreted in light of APOE genotypes for future clinical applications.

BackgroundAlthough clozapine is the most effective antipsychotic drug for treatment-resistant schizophrenia, it leads to a poor or partial response in 40 to 70% of patients. Augmentation of clozapine with electroconvulsive therapy (ECT) is a highly effective and relatively safe treatment for these clozapine-resistant patients. However, parameters are not yet well specified, such as the optimal number of sessions, their frequency, and the relevance of maintenance ECT. Our objective is to compare the efficacy and tolerance between two protocols of combined ECT and clozapine treatment in patients with ultra-resistant schizophrenia (URS): a 6-month protocol (short protocol with 20 ECT sessions) and a 12-month protocol (long protocol with 40 ECT sessions).MethodsSixty-four patients with schizophrenia with persistent psychotic symptoms despite clozapine treatment will be enrolled in a prospective multicentric assessor-blinded randomized controlled trial. Patients will be randomly assigned to the short or the long protocol. The main outcome is the response rate assessed by the Positive and Negative Symptoms Scale (PANSS) 3 months after the end of the treatment in patients following the long protocol compared to those following the short protocol. The response was defined as a 30% reduction on the PANSS baseline. Clinical assessments (PANSS, BPRS, HAMD-21, YMRS, CGI, GAF, Modified Overt Aggression Scale (MOAS), and Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS)) and plasma clozapine concentration will be performed at baseline and at 2, 4, 6, 9, 12, and 15 months. Neuropsychological measures (MMSE, RL/RI-16, Doors test, D2 Test of Attention, Copy of the Rey-Osterrieth complex figure) will be performed at baseline and at 6 and 15 months.DiscussionThe aims of this research are to optimize protocols of combined ECT with clozapine in patients with URS and to offer specific recommendations for these patients’ care.Trial registrationClinicalTrials.gov NCT03542903. Registered on May 31, 2018. Id RCB: 2017-A02657-46

IntroductionEsketamine nasal spray has been developed for patients with treatment resistant depression.ObjectivesA cohort Temporary Authorization for Use (ATUc) allowed to collect for a 6-month period the first data in real lifeMethodsOn 02/08/2019 the French National Agency for Medicines and Health Product Safety granted an early access program for Esketamine nasal spray framed by a specific protocol for patients without therapeutic alternatives. Each treatment request was approved based on inclusion and exclusion criteria. Clinical evolution, treatment management and safety were then spontaneously reported by psychiatrists.Results From 09/23/2019 to 03/25/2020, 66 patients were treated. The median age was 53 years and 41 (62.1%) were females. At treatment request, 52 patients (79%), presented a severe current depressive episode based on clinical judgment. The median duration of the disease was 12.2 years and the current episode was 2.6 years. Since the beginning of the current depressive episode, all patients (66) were prescribed ≥2 antidepressants (mean 4.2). Esketamine was initiated in a complete hospitalization setting in 27 patients (55.1%) and in day hospitalization in 22 patients (44.9%).Safety profile was consistent with the one described during clinical study. The most frequently adverse events reported (>10%) were dizziness, sedation, sleepiness, anxiety and dissociation. Most of them appeared after treatment administration and were transient.ConclusionsATUc ended on 12/18/2019 after Marketing Authorization granted by European Medicines Agency. Data reported by French psychiatrists are the first collected in this specific population and provide descriptive information on patient characteristics, burden of disease; Esketamine management and practical use at hospital levelDisclosureData analysis performed by RCTs and poster conception coordinated by Medergy and funded by Janssen

Primary familial brain calcification (PFBC) is a rare cerebral microvascular calcifying disorder with diverse neuropsychiatric expression. Five genes were reported as PFBC causative when carrying pathogenic variants. Haploinsufficiency of SLC20A2, which encodes an inorganic phosphate importer, is a major cause of autosomal-dominant PFBC. However, PFBC remains genetically unexplained in a proportion of patients, suggesting the existence of additional genes or cryptic mutations. We analyzed exome sequencing data of 71 unrelated, genetically unexplained PFBC patients with the aim to detect copy number variations that may disrupt the expression of core PFBC-causing genes. After the identification of a deletion upstream of SLC20A2, we assessed its consequences on gene function by reverse transcriptase droplet digital polymerase chain reaction (RT-ddPCR), an ex vivo inorganic phosphate uptake assay, and introduced the deletion of a putative SLC20A2 enhancer mapping to this region in human embryonic kidney 293 (HEK293) cells by clustered regularly interspaced short palindromic repeats (CRISPR) - CRISPR-associated protein 9 (Cas9). The 8p11.21 deletion, segregating with PFBC in a family, mapped 35 kb upstream of SLC20A2. The deletion carriers/normal controls ratio of relative SLC20A2 mRNA levels was 60.2% (P < 0.001). This was comparable with that of patients carrying an SLC20A2 premature stop codon (63.4%; P < 0.001). The proband exhibited a 39.3% decrease of inorganic phosphate uptake in blood (P = 0.015). In HEK293 cells, we observed a 39.8% decrease in relative SLC20A2 mRNA levels after normalization on DNA copy number (P < 0.001). We identified a deletion of an enhancer of SLC20A2 expression, with carriers showing haploinsufficiency in similar ranges to loss-of-function alleles, and we observed reduced mRNA levels after deleting this element in a cellular model. We propose a 3-step strategy to identify and easily assess the effect of such events. © 2020 International Parkinson and Movement Disorder Society.

Depuis vingt ans existe à Rouen un partenariat entre une équipe mobile psychiatrie précarité ( empp ) et un centre social associatif ayant pour public les gens du voyage de l’agglomération. Il vise l’accès aux soins psychiques de cette population. Quelques principes, rappelés dans ce texte, favorisent l’aspect pratique et incarné de ce travail engagé au profit de personnes peu ou mal demandeuses, évoluant dans des situations socio-anthropologiques complexes, combinant souvent exclusion sociale, différence culturelle et conflits d’appartenance (appartenir à un sous-groupe culturel dans une société dominante globale comporte des difficultés). Nous mettons en avant qu’un rapport contre--transférentiel culturel de nature ambivalente existe, dont nous sommes dépositaires, dont sont dépositaires les personnes que nous souhaitons aider ici. Il nous semble fondamental d’en être conscients pour mener au mieux notre mission. Le rôle du médiateur en santé (précisé dans nos lignes) comme celui des intervenants de l’ empp compose avec cette réalité.

Le travail de psychothérapie à l’adresse de personnes migrantes a été envisagé de différentes façons en France depuis quarante ans, avec une variabilité de l’attention linguistique accordée par chaque dispositif. Depuis les années 1990, le traumatisme psychique d’origine externe est un élément central de nombre de thérapies de migrants. Ce texte met en avant l’intérêt d’un travail psychologique, accessible facilement, dans une langue tierce, et la portée thérapeutique et les effets de soins advenant « quand-même » d’un tel dispositif, c’est-à‑dire malgré l’aspect non idéal du cadre en question.