Search

Juliette Felician,1– 3 Filipe Galvao,3 Mylène Lefebvre,3 Mikail Nourredine,2,4– 6,&ast; Laure Peter-Derex1,2,7,&ast; 1Centre for Sleep Medicine and Respiratory Diseases, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France; 2Medicine faculty, Lyon 1 University, Lyon, France; 3Unité Michel Jouvet – Pôle Est – Z19, Centre Hospitalier Le Vinatier, Bron, France; 4Biostatistics Unit, University Hospital Service of Pharmacotoxicology and Public Health Department, Hospices Civils de Lyon, Lyon, France; 5Research Department, Centre Hospitalier Le Vinatier, Bron, France; 6Biometry and Evolutionary Biology Laboratory, UMR CNRS 5558, Lyon, France; 7Lyon Neuroscience Research Centre, CNRS UMR 5292/INSERM U1028, Lyon, France&ast;These authors contributed equally to this workCorrespondence: Laure Peter-Derex, Centre for Sleep Medicine and Respiratory Diseases, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, 103 Grande Rue de la Croix-Rousse, Lyon, 69004, France, Tel +33 4 72 07 17 69, Fax +33 4 72 07 28 08, Email laure.peter-derex@chu-lyon.frPurpose: The containment of the population during the COVID-19 pandemic led to the emergence or recurrence of psychiatric conditions and sleep disorders. The influence of sleep/wake rhythm on mental health is well known. The objective of our study was to evaluate the link between the shift in sleep/wake rhythm and the presence of depressive symptoms during the March to May 2020 lockdown in the French population.Participants and Methods: Participants (n = 2513) were recruited via newspapers and social networks in March 2020. We evaluated i) the chronotype before and during the lockdown, assessed by the change in mid-sleep time on work-free days corrected for sleep debt on workdays (delta MSFsc); ii) morningness-eveningness circadian preference (Horne & Ostberg questionnaire); iii) depressive symptoms (Patient Health Questionnaire-9, PHQ-9). The delta MSFsc and the PHQ-9 score were compared between circadian preference types. A multivariate model adjusted for age, sex, circadian preference, housing type, and marital status was used to assess the influence of delta MSFsc on the PHQ-9 score in the whole population.Results: The population consisted of 77% women, of median (IQR) age 39 (30– 48) years. Compared with the pre-lockdown period, the median (IQR) MSFsc was shifted by 30 (0– 66) min during the lockdown, with a significant difference between evening [60 (15– 120) min], morning [15 (0– 46) min] and neutral [30 (0– 70) min] circadian type individuals, p < 0.001. One-third of all participants had moderate to severe depressive symptoms (PHQ-9 ≥ 10). A 1-hour shift in MSFsc was associated with a 0.50-point increase [95% CI (0.28; 0.72), p < 0.001] in the PHQ-9.Conclusion: A phase delay in the chronotype was observed in the general population during lockdown. Such disruption was associated with depressive symptoms but the direction of the relationship remains hypothetical. The impact on mental health of preventive measures targeting the sleep/wake rhythm in this context needs further evaluation.Keywords: phase delay, pandemic, containment, mental health, chronotype, circadian preference

The morbidity of aneurysmal subarachnoid hemorrhage (aSAH) remains high, particularly because of secondary cerebral lesions that significantly aggravate the primary lesions. The main type of secondary lesions is delayed cerebral ischemia (DCI), in which platelets (PLT) appear to play a key role. Mean platelet volume (MPV) is an indirect marker of platelet activation. We aimed to determine the individual trajectories of MPV over time in patients with and without DCI during the course of aSAH. This is a single-center, retrospective, longitudinal analysis of individual trajectories of MPV over time, in a cohort of aSAH patients included in the Prospective, Observational Registry of Patient with Subarachnoid Hemorrhage in Neurocritical Care Unit (ProReSHA). A mixed-effects linear regression model was used to compare the trajectories of MPV and MPV/PLT ratio between patients who developed a DCI and those who did not. A total of 3634 MPV values were collected in 587 patients. The analysis of MPV as a function of DCI occurrence showed a significant difference in the trajectory over time between patients with DCI and those without, with an estimate of 0.02 (95%CI 0.01, 0.04, p = 0.009). The analysis of the MPV/PLT ratio as a function of DCI occurrence and other covariates showed a significant difference in the trajectory over time only for patients with a modified Fisher score less than 3, with an estimate of -0.59 (95%CI: -0.94, -0.23, p = 0.001). The individual trajectories of MPV over time differ between patients with DCI and those without. However, MPV values vary greatly over time and between patients. Thus it does not appear as a reliable biomarker for stratifying patients based on their specific risk of developing DCI. ClinicalTrials.gov identifier: (NCT02890004), registered in August 2016., (© 2024. The Author(s).)

Background: Attention-deficit/hyperactivity disorder (ADHD) affects approximately 5% of children globally, with symptoms often persisting into adulthood. While pharmacological interventions are commonly employed for management, understanding the optimal dosing for efficacy and tolerability remains crucial. This study aims to conduct a dose-response network meta-analysis to estimate the efficacy of pharmacological treatments across different doses, aiming to inform clinical decision-making and improve treatment outcomes., Methods: This updated systematic review will include randomized controlled trials evaluating ADHD medication efficacy in children, adolescents, and adults. An updated search from a 2018 NMA will be conducted across multiple electronic databases with no language restrictions, using specific eligibility criteria focused on randomized controlled trials. The primary outcome will assess the severity of ADHD core symptoms, while secondary outcomes will consider treatment tolerability. A dose-response Bayesian hierarchical model will be used to estimate dose-response curves for each medication, identifying optimal dosing strategies., Discussion: With this dose-response network meta-analysis, we aim to better understand the dose-response relationship of pharmacological treatment in ADHD, which could help clinician to the identification of optimal doses., Systematic Review Registration: OSF https://doi.org/10.17605/OSF.IO/3MY4A ., (© 2024. The Author(s).)

Objective: This prospective study aimed to assess couples' psychological status during the perinatal period to identify those at risk for postpartum depression., Methods: Conducted at Lyon University Hospital from March to July 2022, the study enrolled pregnant women without progressive psychiatric disorders or obstetric risk factors, and their partners. Participants completed the Edinburgh Postnatal Depression Scale (EPDS) at three points: during the 9th month of pregnancy, immediate postpartum, and 6-8 weeks after delivery. A score ≥10 on the EPDS indicated depression risk. A score ≥10 on the EPDS indicate depression risk. The primary endpoint was EPDS scores throughout the perinatal period., Results: Ninety-five couples participated; 96% of patients and 68% of partners completed pre-delivery questionnaires, 81% and 71% during maternity stay, and 64% and 46% postpartum, respectively. Overall, 15% of patients and 1% of partners had EPDS scores >10 in the postpartum period. Psychiatric history and emergency cesarean sections were associated with higher immediate postpartum EPDS scores in patients [Beta 3.7 points, 95% CI 0.91; 6.4 and Beta 5.2 points, 2.2; 8.1, respectively]. Episiotomy was associated with higher EPDS scores in partners. No significant association between the different factors studied and the EPDS score was found at 6-8 weeks postpartum in patients nor their partners., Conclusions: While specific risk factors for persistent perinatal depression in couples were not identified, a notable proportion of patients exhibited high EPDS scores. Screening all couples during prepartum and postpartum periods is crucial, regardless of identified risk factors.

Aims: This systematic review and meta-analysis aimed to assess the efficacy of NMDA antagonists in ASD (Autism Spectrum Disorder) on the core (communication and social interaction, repetitive behavior) and associated symptoms (irritability) of ASD, as well as their safety., Methods: PubMed, CENTRAL, CINHAL, EMBASE, and PsycINFO databases were searched until November 2023. Two authors independently selected the studies and extracted data. Randomized controlled trials assessing the efficacy of NMDA receptor antagonists in participants with ASD aged <18 years were included. The quality of the studies was assessed using the Risk of Bias-2 tool. A random-effect meta-analysis model was used to calculate standardized mean differences (SMD) or odds ratios (OR) using meta package in R., Results: This systematic review included ten studies (588 participants). Most studies did not report scales assessing core symptoms of ASD. Meta-analysis of efficacy on ASD core symptoms included three studies (248 participants). NMDA antagonists were not superior to placebo [SMD = 0.29; CI 95% (-1,94; 1.35); I 2 = 0%]. NMDA antagonists was not superior to placebo concerning response (four studies, 189 participants) [OR = 2.4; CI 95% (0.69; 8.38); I 2 = 35%]. Meta-analysis of efficacy on irritability included three studies (186 participants); NMDA antagonists were not superior to placebo [MD irritability = -1.94; CI 95% (-4.66; 0.77); I 2 = 0%]. Compared with placebo, significantly more participants in the NMDA antagonist group reported at least one adverse event (five studies, 310 participants) [OR = 2.04; CI 95% (1.17; 3.57); I 2 = 0%]., Conclusion: Current evidence does not support the effectiveness of NMDA antagonists in the treatment of ASD symptoms or irritability. Further research is needed due to the limited and low quality data available., Systematic Review Registration: PROSPERO CRD42018110399., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Dessus-Gilbert, Nourredine, Zimmer, Rolland, Geoffray, Auffret and Jurek.)

Background and Objectives: While patients with paraneoplastic autoimmune encephalitis (AE) with gamma-aminobutyric-acid B receptor antibodies (GABA B R-AE) have poor functional outcomes and high mortality, the prognosis of nonparaneoplastic cases has not been well studied., Methods: Patients with GABA B R-AE from the French and the Dutch Paraneoplastic Neurologic Syndromes Reference Centers databases were retrospectively included and their data collected; the neurologic outcomes of paraneoplastic and nonparaneoplastic cases were compared. Immunoglobulin G (IgG) isotyping and human leukocyte antigen (HLA) genotyping were performed in patients with available samples., Results: A total of 111 patients (44/111 [40%] women) were enrolled, including 84 of 111 (76%) paraneoplastic and 18 of 111 (16%) nonparaneoplastic cases (cancer status was undetermined for 9 patients). Patients presented with seizures (88/111 [79%]), cognitive impairment (54/111 [49%]), and/or behavioral disorders (34/111 [31%]), and 54 of 111 (50%) were admitted in intensive care unit (ICU). Nonparaneoplastic patients were significantly younger (median age 54 years [range 19-88] vs 67 years [range 50-85] for paraneoplastic cases, p < 0.001) and showed a different demographic distribution. Nonparaneoplastic patients more often had CSF pleocytosis (17/17 [100%] vs 58/78 [74%], p = 0.02), were almost never associated with KTCD16-abs (1/16 [6%] vs 61/70 [87%], p < 0.001), and were more frequently treated with second-line immunotherapy (11/18 [61%] vs 18/82 [22%], p = 0.003). However, no difference of IgG subclass or HLA association was observed, although sample size was small (10 and 26 patients, respectively). After treatment, neurologic outcome was favorable (mRS ≤2) for 13 of 16 (81%) nonparaneoplastic and 37 of 84 (48%) paraneoplastic cases ( p = 0.03), while 3 of 18 (17%) and 42 of 83 (51%) patients had died at last follow-up ( p = 0.008), respectively. Neurologic outcome no longer differed after adjustment for confounding factors but seemed to be negatively associated with increased age and ICU admission. A better survival was associated with nonparaneoplastic cases, a younger age, and the use of immunosuppressive drugs., Discussion: Nonparaneoplastic GABA B R-AE involved younger patients without associated KCTD16-abs and carried better neurologic and vital prognoses than paraneoplastic GABA B R-AE, which might be due to a more intensive treatment strategy. A better understanding of immunologic mechanisms underlying both forms is needed.

Objective: To perform a systematic review and meta-analysis of endoscopic procedures for treating vesico-urethral anastomotic stenosis (VUAS) after prostatectomy, as initial VUAS management remains unclear., Methods: A search of the MEDLINE database, the Cochrane database, and clinicaltrials.gov was performed (last search February 2023) using the following query: (['bladder neck' OR 'vesicourethral anastomotic' OR 'anastomotic'] AND ['stricture' OR 'stenosis' OR 'contracture'] AND 'prostatectomy'). The primary outcome was the success rate of VUAS treatment, defined by the proportion (%) of patients without VUAS recurrence at the end of follow-up., Results: The literature search identified 420 studies. After the screening, 78 reports were assessed for eligibility, and 40 studies were included in the review. The pooled characteristics of the 40 studies provided a total of 1452 patients, with a median (interquartile range [IQR]) follow-up of 23.7 (13-32) months and age of 66 (64-68) years. The overall success rate (95% confidence interval [CI]) of all endoscopic procedures for VUAS treatment was 72.8% (64.4%-79.9%). Meta-regression models showed a negative influence of radiotherapy on the overall success rate (P = 0.012). After trim-and-fill (addition of 10 studies), the corrected overall success rate (95% CI) was 62.9% (53.6%-71.4%)., Conclusion: This first meta-analysis of endoscopic treatment success rate after VUAS reported an overall success rate of 72.8%, lowered to 62.9% after correcting for significant publication bias. This study also highlighted the need for a more thorough reporting of post-prostatectomy VUAS data to understand the treatment pathway and provide higher-quality evidence-based care., (© 2023 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background: Lamotrigine has become one of the most commonly prescribed antiseizure medications (ASM) in epileptic women during pregnancy and therefore requires regular updates regarding its safety. The aim of this study was to estimate the association between in utero exposure to lamotrigine monotherapy and the occurrence of neurodevelopmental outcomes., Methods: All comparative studies assessing the occurrence of neurodevelopmental outcomes after epilepsy-indicated lamotrigine monotherapy exposure during pregnancy were searched. First, references were identified through a snowballing approach, then, through electronic databases (Medline and Embase) from 2015 to June 2022. One investigator evaluated study eligibility and extracted data and a second independent investigator reviewed the meta-analysis (MA). A systematic review and random-effects model approach were performed using a collaborative WEB-based meta-analysis platform (metaPreg.org) with a registered protocol (osf.io/u4gva)., Results: Overall, 18 studies were included. For outcomes reported by at least 4 studies, the pooled odds ratios and 95% confidence interval obtained with the number of exposed (N1) and unexposed children (N0) included were: neurodevelopmental disorders as a whole 0.84 [0.66;1.06] (N1 = 5,271; N0 = 22,230); language disorders or delay 1.16 [0.67;2.00] (N1 = 313; N0 = 506); diagnosis or risk of ASD 0.97 [0.61;1.53] (N1 = at least 5,262; N0 = 33,313); diagnosis or risk of ADHD 1.14 [0.75;1.72] (N1 = at least 113; N0 = 11,530) and psychomotor developmental disorders or delay 2.68 [1.29-5.56] (N1 = 163; N0 = 220). The MA of cognitive outcomes included less than 4 studies and retrieved a significant association for infants exposed to lamotrigine younger than 3 years old but not in the older age groups., Conclusion: Prenatal exposure to lamotrigine monotherapy is not found to be statistically associated with neurodevelopmental disorders as a whole, language disorders or delay, diagnosis or risk of ASD and diagnosis or risk of ADHD. However, the MA found an increased risk of psychomotor developmental disorders or delay and cognitive developmental delay in less than 3 years old children. Nevertheless, these findings were based exclusively on observational studies presenting biases and on a limited number of included children. More studies should assess neurodevelopmental outcomes in children prenatally exposed to lamotrigine., (© 2024. The Author(s).)

Background: To evaluate the contribution of chest X-ray and chest CT for the diagnosis of sarcoid uveitis., Methods: Retrospective study on consecutive patients with uveitis of unknown etiology, who underwent both chest X-ray and CT during uveitis diagnosis workup in a tertiary French university hospital., Results: A total of 914 patients were included. Systemic sarcoidosis was identified in 23.1%. The probability of discordance between chest X-ray and CT increased with age at diagnosis ( p  < 0.001). In patients 30 years of age and younger, the probability of discordance was 5% or less, and 0.8% if the ACE level was normal. After 78.3 years of age, the probability of discordance was 20% or more., Conclusion: We recommend not to perform CT in patients under 30 years of age with a normal chest X ray and ACE level, and suggest performing chest CT first in the elderly.

Background: Impulse control disorders (ICDs) are frequently encountered in Parkinson's disease (PD)., Objectives: We aimed to assess whether clonidine, an α2-adrenergic receptor agonist, would improve ICDs., Methods: We conducted a multicentre trial in five movement disorder departments. Patients with PD and ICDs (n = 41) were enrolled in an 8-week, randomised (1:1), double-blind, placebo-controlled study of clonidine (75 μg twice a day). Randomisation and allocation to the trial group were carried out by a central computer system. The primary outcome was the change at 8 weeks in symptom severity using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) score. A reduction of the most elevated subscore of the QUIP-RS of more than 3 points without any increase in the other QUIP-RS dimension defined success., Results: Between 15 May 2019 and 10 September 2021, 19 patients in the clonidine group and 20 patients in the placebo group were enrolled. The proportion difference of success in reducing QUIP-RS at 8 weeks, was 7% (one-sided upper 90% CI 27%) with 42.1% of success in the clonidine group and 35.0% in the placebo group. Compared to patients in the placebo group, patients in the clonidine group experienced a greater reduction in the total QUIP-RS score at 8 weeks (11.0 points vs. 3.6)., Discussion: Clonidine was well tolerated but our study was not enough powerful to demonstrate significant superiority compared to placebo in reducing ICDs despite a greater reduction of total QUIP score at 8 weeks. A phase 3 study should be conducted., Trial Registration: The study was registered (NCT03552068) on clinicaltrials.gov on June 11, 2018., (© 2023. The Author(s).)

Background: The association between cannabis use and positive symptoms in schizophrenia spectrum disorders is well documented, especially via meta-analyses. Yet, findings are inconsistent regarding negative symptoms, while other dimensions such as disorganization, depression, and excitement, have not been investigated. In addition, meta-analyses use aggregated data discarding important confounding variables which is a source of bias., Methods: PubMed, ScienceDirect and PsycINFO were used to search for publications from inception to September 27, 2022. We contacted the authors of relevant studies to extract raw datasets and perform an Individual Participant Data meta-analysis (IPDMA). Inclusion criteria were: psychopathology of individuals with schizophrenia spectrum disorders assessed by the Positive and Negative Syndrome Scale (PANSS); cannabis-users had to either have a diagnosis of cannabis use disorder or use cannabis at least twice a week. The main outcomes were the PANSS subscores extracted via the 3-factor (positive, negative and general) and 5-factor (positive, negative, disorganization, depression, excitement) structures. Preregistration is accessible via Prospero: ID CRD42022329172., Findings: Among the 1149 identified studies, 65 were eligible and 21 datasets were shared, totaling 3677 IPD and 3053 complete cases. The adjusted multivariate analysis revealed that relative to non-use, cannabis use was associated with higher severity of positive dimension (3-factor: Adjusted Mean Difference, aMD = 0.34, 95% Confidence Interval, CI = [0.03; 0.66]; 5-factor: aMD = 0.38, 95% CI = [0.08; 0.63]), lower severity of negative dimension (3-factor: aMD = -0.49, 95% CI [-0.90; -0.09]; 5-factor: aMD = -0.50, 95% CI = [-0.91; -0.08]), higher severity of excitement dimension (aMD = 0.16, 95% CI = [0.03; 0.28]). No association was found between cannabis use and disorganization (aMD = -0.13, 95% CI = [-0.42; 0.17]) or depression (aMD = -0.14, 95% CI = [-0.34; 0.06])., Interpretation: No causal relationship can be inferred from the current results. The findings could be in favor of both a detrimental and beneficial effect of cannabis on positive and negative symptoms, respectively. Longitudinal designs are needed to understand the role of cannabis is this association. The reported effect sizes are small and CIs are wide, the interpretation of findings should be taken with caution., Funding: This research did not receive any specific grant or funding. Primary financial support for authors was provided by Le Vinatier Psychiatric Hospital., Competing Interests: OA received consulting fees from Cortechs. ai, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Janssen, Sunovion, Lundbeck (all to him personally). EF received consulting fees; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events; support for attending meetings and/or travel; participation on a Data Safety Monitoring Board or Advisory Board from Boehringer-Ingelheim, Janssen, Lundbeck, Otsuka. TW received honoraria for speakership by ROVI, Janssen-Cilag, Recordati; support for participation in APA congress in 2023 by ROVI; participation on a Data Safety Monitoring Board or Advisory Board for DFG sponsored studies, NicStim, Target Flame, Early member in DSMB, member in advisory board of Otsuka/Lundbeck, Janssen-Cilag and ROVI. JA declared support for the present manuscript through payments made to the University of Calgary from NIMH, from 2008 to 2014. OA declared support for the present manuscript through payments made to institution from KG Jebsen Stiftelsen, Research Council Norway, EU H2020 and Horiz Europe, NIMH, Regional Health Authorities, and NordForsk. MS declared support for the present manuscript through initial data collection supported by Grant No. 02.001033 from the Swiss Federal Office of Public Health. RR declared support for the present manuscript from Canada First Research Excellence Fund, Grant doe Healthy Brains for Healthy Lives; Fonds de recherche du Québec – Santé. No other disclosures were reported. All other authors declare no competing interests., (© 2023 The Authors.)

Introduction: Vitamin C is an essential micronutrient playing crucial roles in human biology. Hypovitaminosis C is defined by a plasmatic ascorbemia below 23 µmol/L and is associated with numerous outcomes such as cardiovascular diseases, cancers or neurocognitive disorders. Numerous risk factors are common among older adults making them particularly susceptible to hypovitaminosis C. These risk factors include reduced vitamin intakes, higher vitamin metabolism related to polypathology, and iatrogeny because of polypharmacy. However, the precise prevalence of hypovitaminosis C and its risk factors are poorly documented within the geriatric population.A better knowledge of hypovitaminosis C prevalence and risk factor may lead to improving the vitamin C status among older people and prevent its consequences., Method and Analysis: To answer these questions, we designed a monocentric cross-sectional study in a population of older hospitalised patients in Lyon, France. A sample size of 385 patients was needed to estimate hypovitaminosis C prevalence. The study was proposed to all eligible patient aged more than 75 years old entering the participating acute geriatric unit. The plasmatic vitamin C status was systematically assessed for participating patients, and variables part of the medical and geriatric evaluation were collected. For patients with severe vitamin C depletion, an oral supplementation and a follow-up phone call were organised to ensure treatment completion and tolerance., Ethics and Dissemination: The protocol has been approved by an independent national ethics committee and meets the methodological requirements. Final outcomes will be published in a peer-reviewed journal and disseminated through conferences., Trial Registration Number: NCT05668663., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Knowledge about the risks of drugs during pregnancy is continuously evolving due to the frequent publication of a large number of epidemiological studies. Systematic reviews and meta-analyses therefore need to be regularly updated to reflect these advances. To improve dissemination of this updated information, we developed an initiative of real-time full-scale living meta-analyses relying on an open online dissemination platform ( www.metapreg.org )., Method: All living meta-analyses performed in this project will be conducted in accordance with this master protocol after adaptation of the search strategy. A systematic literature search of PubMed and Embase will be performed. All analytical studies (e.g., cohort, case-control, randomized studies) reporting original empirical findings on the association between in utero exposure to drugs and adverse pregnancy outcomes will be included. Study screening and data extraction will be performed in a semi-automation way supervised by a biocurator. A risk of bias will be assessed using the ROBINS-I tools. All clinically relevant pregnancy adverse outcomes (malformations, stillbirths, neuro-developmental disorders, pre-eclampsia, etc.) available in the included studies will be pooled through random-effects meta-analysis. Heterogeneity will be evaluated by I 2 statistics., Discussion: Our living systematic reviews and subsequent updates will inform the medical, regulatory, and health policy communities as the news results evolve to guide decisions on the proper use of drugs during the pregnancy., Systematic Review Registration: Open Science Framework (OSF) registries., (© 2023. The Author(s).)

Background: Patients with pre-stroke disability, defined as a modified Rankin Scale (mRS) ≥3, were excluded from most trials of endovascular thrombectomy (EVT) for acute stroke. We sought to evaluate the prognostic factors associated with favorable outcome in stroke patients with known disability undergoing EVT, and the impact of successful reperfusion., Methods: Consecutive acute stroke patients with pre-stroke disability, undergoing EVT, were retrospectively collected between 2016 to 2019 from a Canadian cohort and a multicenter French cohort (Endovascular Treatment in Ischemic Stroke registry-ETIS). Favorable outcome was defined as an mRS equal to pre-stroke mRS. Patients achieving successful reperfusion (defined as a modified Thrombolysis in Cerebral Infarction score of 2b/3) were compared with patients without successful reperfusion to determine if successful EVT was associated with better functional outcomes., Results: Among 6220 patients treated with EVT, 280 (4.5%) patients with a pre-stroke mRS ≥3 were included. Sixty-one patients (21.8%) had a favorable outcome and 146 (52.1%) died at 3 months. Patients with successful reperfusion had a higher proportion of favorable 90-day mRS (27.6% versus 19.6%, p = 0.025) and a lower mortality (48.3% versus 69.6%, p = 0.008) than patients without successful reperfusion. After adjusting for baseline prognostic factors, successful reperfusion defined by TICI ≥2b was associated with favorable functional outcome (OR 3.16 CI95% [1.11-11.5]; p 0.048)., Conclusion: In patients with pre-stroke disability, successful reperfusion is associated with a greater proportion of favorable outcome and lower mortality., Competing Interests: Declaration of Competing Interest Authors declare no conflicts of interests., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: Antipsychotics are used in a large variety of psychiatric and neurological disorders; investigating their use in real life is important to understand national prescribing practices, as well as to determine the levels of patient adherence., Methods: Using a 1/97e random sample (General Sample of Beneficiaries, EGB) of the French health insurance reimbursement database, we conducted a historical cohort study on the 2007-2017 period. The aim was to describe the sociodemographic characteristics of patients, the types of antipsychotics dispensed, the types of prescribers, the mean doses and average durations of treatment, the co-dispensed medications, and the levels of adherence to treatment. To exclude punctual uses of antipsychotics, we selected only patients with a continuous dispensing of the same antipsychotic over at least 3 months., Results: In total, 13,799 subjects (1.66% of the EGB sample) were included (56.0% females; mean age 55.8 ± 19.4 years). Risperidone (19.3%), cyamemazine (18.7%), olanzapine (11.9%), tiapride (8.8%), and haloperidol (7.5%) were the five most prescribed antipsychotics. 44.9% of prescriptions were written by general practitioners, 34.1% by hospital practitioners, and 18.4% by private-practice psychiatrists. On average, the mean dispensed doses were relatively low, but the variation range was large. Long-acting forms were used in 5.4% of the sample, and clozapine in 1.3%. 34.2% of patients received more than one antipsychotic, and almost 15% were prescribed at least three concomitant antipsychotics. Paliperidone and clozapine were associated with the highest levels of adherence, and risperidone and haloperidol with the lowest ones., Conclusion: An important heterogeneity of antipsychotic prescribing practices was observed in France. The rate of use of long-acting antipsychotics was low, whereas multiple antipsychotic prescriptions were frequent., Competing Interests: Author BR received fees for consultancy or lectures, or research grants (but not for this study), from Gilead, Abbvie, MSD, Ethypharm, Indivior, Camurus, Recordati, Grü; nenthal, Janssen, Accord Healthcare, PolPharma, Lundbeck, Zentiva, Shire, HAC Pharma, Panaxia, and PileJe. Authors FD, MBér, FJ, and MBel were employed by PELyon. Author EV received grants and personal fees from PELyon, outside the submitted work. Author NG declared to have been invited to a congress by Janssen-Cilag. Author LC reported having received lecture and expertise fees and conference fundings from Indivior. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rolland, Dalon, Gauthier, Nourredine, Bérard, Carton, Brousse, Llorca, Jacoud, Van Ganse and Belhassen.)

Formal thought disorder (FTD) is a multidimensional syndrome mainly occurring along the psychosis continuum. Cannabis use is known to increase symptoms of psychosis, particularly positive symptoms. However, the impact of cannabis use on FTD in individuals presenting symptoms along the psychosis continuum remains unclear. To address this knowledge gap, we conducted a meta-analysis examining the association between cannabis use and FTD in those individuals. We hypothesized that cannabis would worsen FTD. We conducted a systematic search of the PubMed, ScienceDirect, PsycINFO, Web of Science, Embase and Google Scholar databases up to July 2022. The results were collated through a random-effects model using the statistical software R. Reference lists of included studies were searched for additional relevant publications. Nineteen studies were included, totalling 1840 cannabis users and 3351 non-cannabis users. The severity of FTD was found to be higher in cannabis users (SMD = 0.21, 95%CI [0.12-0.29], p = 0.00009). Subgroup analyses revealed that FTD severity was increased among cannabis users, regardless of the disorder severity: healthy individuals (SMD = 0.19, 95%CI [0.05-0.33], p = 0.02); patients with first-episode psychosis (SMD = 0.21, 95%CI [0.01-0.41], p = 0.04); patients with schizophrenia (SMD = 0.25, 95%CI [0.11-0.38], p = 0.005). Between-group differences were not significant. In line with its already known effect on positive symptoms in psychosis, cannabis use appears to be associated with increased FTD severity all along the psychosis continuum. Future research should consider potential confounding variables such as other substance use disorders and explore how FTD dimensions are impacted by cannabis use., (© 2022. The Author(s).)

In this one-year prospective study, Parkinson's disease (PD) patients with or without mania following STN-DBS were compared to investigate risk and etiological factors, clinical management and consequences. Eighteen (16.2%) out of 111 consecutive PD patients developed mania, of whom 17 were males. No preoperative risk factor was identified. Postoperative mania was related to ventral limbic subthalamic stimulation in 15 (83%) patients, and resolved as stimulation was relocated to the sensorimotor STN, besides discontinuation or reduction of dopamine agonists and use of low-dose clozapine in 12 patients, while motor and nonmotor outcomes were similar. These findings underpin the prominent role of limbic subthalamic stimulation in postoperative mania. ANN NEUROL 2022;92:411-417., (© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Concerns have been raised about early vs. later impacts of the COVID-19 pandemic on suicidal behavior. However, data remain sparse to date. We investigated all calls for intentional drug or other toxic ingestions to the eight Poison Control Centers in France between 1st January 2018 and 31st May 2022. Data were extracted from the French National Database of Poisonings. Calls during the study period were analyzed using time trends and time series analyses with SARIMA models (based on the first two years). Breakpoints were determined using Chow test. These analyses were performed together with examination of age groups (≤ 11, 12-24, 25-64, ≥ 65 years) and gender effects when possible. Over the studied period, 66,589 calls for suicide attempts were received. Overall, there was a downward trend from 2018, which slowed down in October 2019 and was followed by an increase from November 2020. Number of calls observed during the COVID period were above what was expected. However, important differences were found according to age and gender. The increase in calls from mid-2020 was particularly observed in young females, while middle-aged adults showed a persisting decrease. An increase in older-aged people was observed from mid-2019 and persisted during the pandemic. The pandemic may therefore have exacerbated a pre-existing fragile situation in adolescents and old-aged people. This study emphasizes the rapidly evolving situation regarding suicidal behaviour during the pandemic, the possibility of age and gender differences in impact, and the value of having access to real-time information to monitor suicidal acts., (© 2022. The Author(s).)

Excessive alcohol consumption is the leading cause of liver diseases in Western countries, especially in France. Alcohol-related liver disease (ARLD) is an extremely broad context and there remains much to accomplish in terms of identifying patients, improving prognosis and treatment, and standardising practices. The French Association for the Study of the Liver wished to organise guidelines together with the French Alcohol Society in order to summarise the best evidence available about several key clinical points in ARLD. These guidelines have been elaborated based on the level of evidence available in the literature and each recommendation has been analysed, discussed and voted by the panel of experts. They describe how patients with ARLD should be managed nowadays and discuss the main unsettled issues in the field., (© 2022 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Background: Gabapentinoids (i.e., gabapentin and pregabalin) are medications approved for epilepsy, chronic pain, or generalized anxiety disorder. Recently, there have been regular reports of misuse of pregabalin, and to a lesser extent, gabapentin, in particular among opioid and polydrug users., Objectives: To longitudinally explore the amounts of gabapentinoids dispensed in Lyon's Permanent Access to Healthcare (PASS) units, which offer permanent and free healthcare to precarious populations with no healthcare insurance coverage., Methods: We collected the amounts of pregabalin and gabapentin dispensed in the three PASS units of Lyon and calculated the average doses dispensed monthly between 2016 and the first quarter of 2021 (1Q2021), with and without adjustment for the number of dispensing visits., Results: The total doses of gabapentinoid dispensed every month in Lyon's PASS units displayed a 1233% increase for pregabalin, and a 1185% increase for gabapentin, between 2016 and 1Q2021. When adjusted for the number of visits, this increase reached a factor of 8.5 for pregabalin and 8.3 for gabapentin, respectively. However, while the increase in pregabalin dispensing was constant throughout the study period, gabapentin total dispensed doses were more fluctuating over time, and the rise of dispensations was thus less straightforward., Conclusion: Our study reveals a local but substantial increase in gabapentinoid use in populations with no social insurance. These findings should be confirmed more widely and plead for the systematic collection of anonymous patient data in free healthcare centers in France., (© 2021 Société Française de Pharmacologie et de Thérapeutique.)

Impulsivity is an important transdiagnostic feature of many psychiatric disorders, as well as a marker of poorer outcome. Topiramate is broadly used for reducing impulsivity in various neuropsychiatric disorders, but no systematic review or meta-analysis has ever explored whether evidence supports this clinical use. We conducted a systematic review and meta-analysis of the literature, using PubMed, PsycInfo and Cochrane databases. We included all studies assessing the efficacy of topiramate in adults with high levels of impulsivity, based on either psychometric or neuropsychological measures. Seven articles were included, involving 578 participants. Important heterogeneity in designs and quality features was observed. Topiramate lowered impulsivity levels in two of the studies that used the Barratt Impulsiveness Scale (BIS) (401 participants) and in one of the studies that used neuropsychological measures (63 participants). Four other studies found no effect of topiramate on impulsivity. A larger reduction in the BIS-11 overall score, with a mean difference of 2.57 (95% confidence interval -4.12 to -1.02), was found in the topiramate group than the placebo group using a random effects model. However, one study accounted for the major part (85.5%) of it, and most included studies presented a high risk of bias. The use of a self-assessment scale induced an additional risk of self-report bias. No clear-cut evidence was found for a transdiagnostic effectiveness of topiramate in reducing impulsivity levels. However, encouraging results were found in some specific disorders., (© 2021 Société Française de Pharmacologie et de Thérapeutique.)

The search for a biological marker predicting the future failure or success of electroconvulsive therapy (ECT) remains highly challenging for patients with treatment-resistant depression. Evidence suggests that Brain-Derived Neurotrophic Factor (BDNF), a protein known to be involved in brain plasticity mechanisms, can play a key role in both the clinical efficacy of ECT and the pathophysiology of depressive disorders. We hypothesized that mature BDNF (mBDNF), an isoform of BDNF involved in the neural plasticity and survival of neural networks, might be a good candidate for predicting the efficacy of ECT. Total BDNF (tBDNF) and mBDNF levels were measured in 23 patients with severe treatment-resistant depression before (baseline) they received a course of ECT. More precisely, tBDNF and mBDNF measured before ECT were compared between patients who achieved the criteria of remission after the ECT course (remitters, n = 7) and those who did not (non-remitters, n = 16). We found that at baseline, future remitters displayed significantly higher mBDNF levels than future non-remitters ( p = 0.04). No differences were observed regarding tBDNF levels at baseline. The multiple logistic regression model controlled for age and sex revealed that having a higher baseline mBDNF level was significantly associated with future remission after ECT sessions (odd ratio = 1.38; 95% confidence interval = 1.07-2.02, p = 0.04). Despite the limitations of the study, current findings provide additional elements regarding the major role of BDNF and especially the mBDNF isoform in the clinical response to ECT in major depression.

Even though tobacco-induced sleep disturbances (TISDs) have been reported in previous studies, the present article is the first meta-analysis quantitatively assessing the impact of tobacco on sleep parameters. We conducted a systematic review and meta-analysis of the studies comparing objective (i.e. polysomnography and actigraphy) and/or subjective sleep parameters in chronic tobacco smokers without comorbidities versus healthy controls. Studies were retrieved using PubMed, PsycINFO, and Web of Science. Differences are expressed as standardized mean deviations (SMD) and their 95% confidence intervals (95%CI). Fourteen studies were finally included into the review, among which ten were suitable for meta-analysis. Compared to healthy controls, chronic tobacco users displayed increased N1 percentage (SMD = 0.65, 95%CI: 0.22 to 1.07), N2 percentage (SMD = 1.45, 95%CI: 0.26 to 2.63), wake time after sleep onset (SMD = 6.37, 95%CI: 2.48 to 10.26), and decreased slow-wave sleep (SMD = -2.00, 95%CI: -3.30 to -0.70). Objective TISDs preferentially occurred during the first part of the night. Regarding subjective parameters, only the Pittsburgh Sleep Quality Index (PSQI) total score could be analyzed, with no significant between-groups difference (SMD = 0.53, 95%CI: -0.18 to 1.23). Smoking status should be carefully assessed in sleep medicine, while TISDs should be regularly explored in chronic tobacco users., Competing Interests: Conflicts of interest The authors do not have any conflicts of interest to disclose., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: To assess the efficacy and safety of topiramate in treating binge eating disorder (BED), using a systematic review and meta-analysis of the available randomized clinical trials (RCTs)., Methods: The RCTs assessing topiramate vs placebo with or without adjunctive psychotherapy in BED were reviewed using a systematic search in the PubMed, Web of Science, PsycINFO, Cochrane Database of Systematic Review, and ClinicalTrials.gov search Websites, from inception to November 2019. Main outcomes were the changes in binge frequency, quality of life, and weight, respectively. Effect estimates were pooled using random-effect models and presented as risk ratios (RRs) or mean differences (MDs) and their 95% confidence interval (95% CI). Data extraction was performed by two independent reviewers., Results: Three studies were eligible for inclusion, involving 528 BED patients. Topiramate was found to be significantly more efficacious than placebo in reducing: (a) the number of binge episodes per week (MD = -1.31; 95% CI = -2.58 to -0.03; I2 = 94%); (b) the number of binge days per week (MD = -0.98; 95% CI = -1.80 to -0.16; I2 = 94%); and (c) weight (MD = -4.91 kg; 95% CI = -6.42 to -3.41; I2 = 10%). However, participants in the topiramate groups withdrew significantly more frequently for safety reasons, relative to placebo participants (RR = 1.90; 95% CI = 1.13-3.18, I2 = 0%)., Conclusions: Preliminary findings support a possible efficacy of topiramate for the treatment of BED, even if safety concerns could limit the practical use of this treatment in BED subjects.

FcRn plays a major role in regulating immune homeostasis, but it is also able to transport biologics across cellular barriers. The question of whether FcRn could be an efficient transporter of biologics across the nasal epithelial barrier is of particular interest, as it would allow a less invasive strategy for the administration of biologics in comparison to subcutaneous, intramuscular or intravenous administrations, which are often used in clinical practice. A focused systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. It was registered on the international prospective register of systematic reviews PROSPERO, which helped in identifying articles that met the inclusion criteria. Clinical and preclinical studies involving FcRn and the nasal delivery of biologics were screened, and the risk of bias was assessed across studies using the Oral Health Assessment Tool (OHAT). Among the 12 studies finally included in this systematic review (out of the 758 studies screened), 11 demonstrated efficient transcytosis of biologics through the nasal epithelium. Only three studies evaluated the potential toxicity of biologics' intranasal delivery, and they all showed that it was safe. This systematic review confirmed that FcRn is expressed in the nasal airway and the olfactory epithelium, and that FcRn may play a role in IgG and/or IgG-derived molecule-transcytosis across the airway epithelium. However, additional research is needed to better characterize the pharmacokinetic and pharmacodynamic properties of biologics after their intranasal delivery.

Importance: Growing evidence supports an association between attention-deficit/hyperactivity disorder (ADHD) in childhood and subsequent psychotic disorders. Both disorders share physiopathological features such as attention deficits, dopaminergic imbalance, and genetic susceptibility. However, the results of epidemiologic studies have been conflicting., Objective: To provide a quantitative synthesis of studies exploring the association between ADHD and the risk of subsequent psychotic disorder., Data Sources: A systematic literature search of the MEDLINE, Scopus, PsycInfo, and Web of Science databases was performed from inception until the final analysis on July 7, 2020. No restriction of language was applied., Study Selection: Cohort and case-control studies examining the relative risk of developing a psychotic disorder in people diagnosed with ADHD at younger than 18 years compared with control individuals without ADHD., Data Extraction and Synthesis: Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed in reporting results. Two independent reviewers extracted the data and assessed the risk of bias of individual studies using the Newcastle-Ottawa Scale. Preferably adjusted odds ratios (aORs) or hazard ratios from the identified studies were extracted, and ORs were computed when they were not adjusted. A random-effects model was used to calculate the pooled relative effect using the meta package in R., Main Outcomes and Measures: An association between ADHD (exposure) and psychotic disorder (outcomes); both diagnoses were based on international classification., Results: A total of 15 studies were included in the review. Twelve studies were pooled in the meta-analysis, representing 1.85 million participants. A diagnosis of ADHD in childhood was associated with a significant increase in the risk of subsequent psychotic disorder, with a pooled relative effect of 4.74 (95% CI, 4.11-5.46; I2 = 43% [95% CI, 0%-70%]). No significant between-group differences were found for subgroup analyses according to psychotic disorder (odds ratio [OR], 5.04; 95% CI, 4.36-5.83) or schizophrenia (OR, 4.59; 95% CI, 3.83-5.50) outcomes, cohort (OR, 4.64; 95% CI, 4.04-5.34) or case-control (OR, 6.81; 95% CI, 4.21-11.03) study design, and adjusted (OR, 4.72; 95% CI, 4.11-5.46) or unadjusted (OR, 3.81; 95% CI, 1.39-10.49) estimates. Meta-regressions were not significant when sex and bias score were used as covariates. No evidence of publication bias was found., Conclusions and Relevance: These findings suggest that childhood ADHD is associated with an increased risk of a subsequent psychotic disorder. Further studies are required to determine the mechanisms linking these common conditions and whether early intervention for ADHD might reduce the risk of subsequent psychotic disorder.

In the field of substance use disorders (SUDs), medications are frequently labeled according to their main symptomatic effect (e.g., "anticraving drugs") or according to imprecise and sometimes old concepts related to treatment strategies (e.g., "replacement therapies", "antabuse drugs", or "substitution treatments"). By contrast, the neuroscience-based nomenclature (NbN) offers a clearer and more consistent rationale, according to which the main element of classification is based on the pharmacological mode of action of the medication. This review aims to display the different approved treatments used in SUDs, and to discuss the pros and cons of using this new conceptual framework in the field of addiction. According to the NbN classification, medications approved in the different SUDs can be classified in the different following categories: 1) nicotinic drugs; 2) GABAergic drugs; 3) opioid drugs; and 4) others. More specifically, medications can be distinguished between whether they mimic the same pharmacological action of the "substance" whose use should be stopped or reduced, or whether they target other more general pharmacological systems, that are supposed to be common to all SUDs, as they reflect the "universal" addiction process. The NbN offers obvious advantages, compared with previous classifications. In particular, it allows to no longer mix drugs with very different pharmacological targets under the same label. The main limitation of the NbN, when applied to psychopharmacology in general, and to SUDs medications in particular, is that drugs frequently have a "dirty" action, with multiple pharmacological targets. In this respect, it may be hard to classify drugs according to the NbN classification, without making the individual profile of each medicine more complex., (Copyright © 2020. Published by Elsevier Masson SAS.)

Aim: To explore the factors determining the interest in extended-release buprenorphine (XR-BUP) injections among patients receiving opioid agonist treatment (OAT) in France., Methods: 366 patients receiving OAT for opioid use disorder, recruited in 66 French centers, were interviewed from 12/2018 to 05/2019. A structured questionnaire assessed their interest in XR-BUP using a [1-10] Likert scale. 'More' vs. 'less' interested groups were defined using the median score of interest, and their characteristics were explored using adjusted odds ratios (aORs) and 95 % confidence interval (95 %CI). Independent variables were as follows: sociodemographic characteristics, OAT-related features (e.g., type of OAT and prescriber, dosing, or duration of treatment), OAT representations, and personal objectives of treatment., Results: The median interest in XR-BUP was 7 (interquartile range: 3-9) out of 10. The participants who were 'more interested' (i.e. those scoring ≥7) showed no substantial difference in sociodemographic characteristics, relative to the 'less interested' participants. However, they more frequently reported forgetting to take their OAT (OR = 1.81; CI95 % = 1.06-3.10) or reported experiencing situations where taking their OAT was impractical (aOR = 1.69; CI95 % = 1.05-2.73). Their treatment objective was more focused on stopping illicit drugs (aOR = 1.67; 95 %CI = 1.02-2.70), reducing health risks (aOR = 3.57; 95 %CI = 1.67-7.69) and craving (aOR = 2.38; 95 %CI = 1.39-4.02) or improving family (aOR = 1.81; 95 %CI = 1.03-3.13) or professional (aOR = 2.22; 95 %CI = 1.43-3.85) recovery., Conclusions: In France, where the access to OAT is relatively unrestricted, the majority of participants were interested in XR-BUP formulations. Being interested was associated with treatment objectives focused on abstinence and recovery, and with experiencing constraints in taking a daily oral OAT., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Although electroconvulsive therapy (ECT) is a highly effective, safe, and well-tolerated antidepressant treatment for late-life depression (LLD), there is large variability in response rates across individuals. We hypothesized that these variations would be in part explained by the level of vascular risk in this population. We therefore compared response rates to ECT in patients with LLD presenting with or without vascular risk factors (VRF)., Methods: 52 patients with LLD (age > 55) who received a course of ECT were separated into 2 groups according to the presence of VRF (n = 20) or not (n = 32). Framingham score (10-year risk for developing a coronary heart disease) was calculated for each patient. Our primary outcome was the number of responders to ECT in each group (defined as at least 50% decrease of the Montgomery-Åsberg Depression Rating Scale score following ECT course). Scores at the self-rated Beck Depression Inventory are also reported., Results: Patients with VRF presented significant lower response rates to ECT (12 out of 20; 60%) than patients without VRF (30 out of 32; 94%; p = 0.004). A negative correlation was found between Framingham score and changes in depression scores pre/post ECT (r = -0.42; p = 0.0039)., Limitations: Our study was limited by sample size and retrospective design., Conclusion: Patients with LLD and VRF showed lower response rates to ECT than those without VRF. The more the VRF increased, the less the antidepressant effect of ECT was observed. Results are discussed in light of the role of apathy in clinical response to ECT., (Copyright © 2020. Published by Elsevier B.V.)

Background: Cannabidiol (CBD) is a natural component of cannabis that possesses a widespread and complex immunomodulatory, antioxidant, anxiolytic, and antiepileptic properties. Much experimental data suggest that CBD could be used for various purposes in alcohol use disorder (AUD) and alcohol-related damage on the brain and the liver. Aim: To provide a rationale for using CBD to treat human subjects with AUD, based on the findings of experimental studies. Methods: Narrative review of studies pertaining to the assessment of CBD efficiency on drinking reduction, or on the improvement of any aspect of alcohol-related toxicity in AUD. Results: Experimental studies find that CBD reduces the overall level of alcohol drinking in animal models of AUD by reducing ethanol intake, motivation for ethanol, relapse, anxiety, and impulsivity. Moreover, CBD reduces alcohol-related steatosis and fibrosis in the liver by reducing lipid accumulation, stimulating autophagy, modulating inflammation, reducing oxidative stress, and by inducing death of activated hepatic stellate cells. Finally, CBD reduces alcohol-related brain damage, preventing neuronal loss by its antioxidant and immunomodulatory properties. Conclusions: CBD could directly reduce alcohol drinking in subjects with AUD. Any other applications warrant human trials in this population. By reducing alcohol-related steatosis processes in the liver, and alcohol-related brain damage, CBD could improve both hepatic and neurocognitive outcomes in subjects with AUD, regardless of the individual's drinking trajectory. This might pave the way for testing new harm reduction approaches in AUD, in order to protect the organs of subjects with an ongoing AUD.

Substance use disorders (SUDs) are associated with impairments of cognitive functions, and cognitive training programs are thus rapidly developing in SUD treatment. However, neuropsychological impairments observed early after withdrawal (i.e., early impairments), that is, approximately in the first six months, may be widespread. Consequently, it might not be possible to train all the identified early impairments. In these situations, we propose that the priority of cognitive training should be given to the early impairments found to be associated with early dropout or relapse (i.e., relapse-related impairments). However, substance-specific relapse-related impairments have not been singled out among all early impairments so far. Using a systematic literature search, we identified the types of established early impairments for all SUDs, and we assessed the extent to which these early impairments were found to be associated with relapse-related impairments. All cognitive functions were investigated according to a classification based on current neuropsychological models, distinguishing classical cognitive, substance-bias, and social cognition systems. According to the current evidence, demonstrated relapse-related impairments in alcohol use disorder comprised impulsivity, long-term memory, and higher-order executive functions. For cannabis use disorder, the identified relapse-related impairments were impulsivity and working memory. For stimulant use disorder, the identified relapse-related impairments were attentional abilities and higher-order executive functions. For opioid use disorder, the only identified relapse-related impairments were higher executive functions. However, many early impairments were not explored with respect to dropout/relapse, particularly for stimulant and opioid use disorders. The current literature reveals substance-specific relapse-related impairments, which supports a pragmatic patient-tailored approach for defining which early impairments should be prioritized in terms of training among patients with SUDs.

The serotonin syndrome is a potentially deadly complication resulting from drug adverse effect, drug-drug interaction or overdose involving one or more serotonergic molecules, e.g., antidepressants, psychostimulants and sometimes an "ignored" serotonergic compound. The serotonin syndrome typically consists of a clinical triad including cognitive/behavioral, neurovegetative and neuromuscular features. However, this syndrome is characterized by major clinical heterogeneity, making the diagnosis difficult in practice. Moreover, many practitioners are quite unaware of this syndrome. Available scores and classifications can help physicians in their diagnosis approach. Knowing the responsible molecules, their potential interactions and mechanisms of action can help preventing this complication allowing therapeutic education among patients. This updated article reviews the clinical presentation, prevention, management, and pathophysiology of the serotonin syndrome, and addresses the most recent advances in pharmacogenetics regarding this syndrome., (Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Sequence-specific binding by the human p53 master regulator is critical to its tumor suppressor activity in response to environmental stresses. p53 binds as a tetramer to two decameric half-sites separated by 0-13 nucleotides (nt), originally defined by the consensus RRRCWWGYYY (n = 0-13) RRRCWWGYYY. To better understand the role of sequence, organization, and level of p53 on transactivation at target response elements (REs) by wild type (WT) and mutant p53, we deconstructed the functional p53 canonical consensus sequence using budding yeast and human cell systems. Contrary to early reports on binding in vitro, small increases in distance between decamer half-sites greatly reduces p53 transactivation, as demonstrated for the natural TIGER RE. This was confirmed with human cell extracts using a newly developed, semi-in vitro microsphere binding assay. These results contrast with the synergistic increase in transactivation from a pair of weak, full-site REs in the MDM2 promoter that are separated by an evolutionary conserved 17 bp spacer. Surprisingly, there can be substantial transactivation at noncanonical (1/2)-(a single decamer) and (3/4)-sites, some of which were originally classified as biologically relevant canonical consensus sequences including PIDD and Apaf-1. p53 family members p63 and p73 yielded similar results. Efficient transactivation from noncanonical elements requires tetrameric p53, and the presence of the carboxy terminal, non-specific DNA binding domain enhanced transactivation from noncanonical sequences. Our findings demonstrate that RE sequence, organization, and level of p53 can strongly impact p53-mediated transactivation, thereby changing the view of what constitutes a functional p53 target. Importantly, inclusion of (1/2)- and (3/4)-site REs greatly expands the p53 master regulatory network., Competing Interests: The authors have declared that no competing interests exist.

The authors report their experience with dual-chamber pacing in hypertrophy obstructive cardiomyopathy. 22 patients (14 women and 8 men) mean age 60 +/- 13 years were implanted between 1992 and 1998. The criteria for pace-maker implantation were the presence of severe symptoms related with hypertrophy obstructive cardiomyopathy (dyspnea, angina, syncope) and left ventricular outflow tract gradient at mean 30 mmHg. Before pacing, all patients received a medical therapy which included beta-blockers or calcium inhibitors. This treatment was considered as ineffective or responsible of side effects. Patients were followed-up at mean 35.1 +/- 20.3 months. During this period, symptoms improved (mean NYHA class 2.7 +/- 0.5 before pacing vs 1.4 +/- 0.5 after pacing) and left ventricular outflow tract lowered from 95.4 +/- 40.8 to 39.3 +/- 20.5 at 6 months. 34.3 +/- 23.4 at one year and 26.5 +/- 21 at the end of follow-up. Seven patients had RF ablation of atrio-ventricular junction for paroxysmal atrial fibrillation or for lack of hemodynamic improvement with pacing. This procedure permits a significative lowering of gradient and a better ventricular filling. In conclusion, dual-chamber pacing is effective for treatment of hypertrophy obstructive cardiomyopathy when medical therapy is ineffective or bad tolerated at condition of: perfect pacing with permanent ventricular capture and optimal AV delay; RF ablation of AV junction in one third of cases; medical therapy systematically associated in all patients.