Comparative Study of Paraneoplastic and Nonparaneoplastic Autoimmune Encephalitis With GABABR Antibodies.

BACKGROUND AND OBJECTIVES: While patients with paraneoplastic autoimmune encephalitis (AE) with gamma-aminobutyric-acid B receptor antibodies (GABABR-AE) have poor functional outcomes and high mortality, the prognosis of nonparaneoplastic cases has not been well studied. METHODS: Patients with GABABR-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 GABABR-AE involved younger patients without associated KCTD16-abs and carried better neurologic and vital prognoses than paraneoplastic GABABR-AE, which might be due to a more intensive treatment strategy. A better understanding of immunologic mechanisms underlying both forms is needed.

Neurodevelopmental outcomes after prenatal exposure to lamotrigine monotherapy in women with epilepsy: a systematic review and meta-analysis.

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.

Post-prostatectomy anastomotic stenosis: systematic review and meta-analysis of endoscopic treatment.

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.

Value of Chest X-Ray and Chest Computed Tomography for Systemic Sarcoidosis Diagnosis in Undifferentiated Uveitis.

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.

Association between cannabis use and symptom dimensions in schizophrenia spectrum disorders: an individual participant data meta-analysis on 3053 individuals.

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.

A cross-sectional study to evaluate hypovitaminosis C prevalence and risk factors in an acute geriatric unit in Lyon, France: the HYPO-VIT-C protocol.

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.

Risk of drug use during pregnancy: master protocol for living systematic reviews and meta-analyses performed in the metaPreg project.

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 I2 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.

Efficacy and safety of clonidine for the treatment of impulse control disorder in Parkinson's disease: a multicenter, parallel, randomised, double-blind, Phase 2b Clinical trial.

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.

Successful thrombectomy is beneficial in patients with pre-stroke disability: Results from an international multicenter cohort study.

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.

Antipsychotic prescribing practices in real-life (APPREAL study): Findings from the French National Healthcare System Database (2007-2017).

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.

Association between formal thought disorder and cannabis use: a systematic review and meta-analysis.

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.

Association of Delayed Sleep/Wake Rhythm with Depression During the First COVID-19 Lockdown in France.

Purpose: 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.

Temporal trends in calls for suicide attempts to poison control centers in France during the COVID-19 pandemic: a nationwide study.

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.

Limbic Stimulation Drives Mania in STN-DBS in Parkinson Disease: A Prospective Study.

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.

Management of alcohol-related liver disease: the French Association for the Study of the Liver and the French Alcohol Society clinical guidelines.

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.

Serum Mature BDNF Level Is Associated with Remission Following ECT in Treatment-Resistant Depression.

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.

Efficacy and safety of topiramate for reducing impulsivity: A transdiagnostic systematic review and meta-analysis of a common clinical use.

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.

Gabapentinoid use in French most precarious populations: Insight from Lyon Permanent Access to Healthcare (PASS) units, 2016-1Q2021.

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.

Tobacco-induced sleep disturbances: A systematic review and meta-analysis.

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.

FcRn as a Transporter for Nasal Delivery of Biologics: A Systematic Review.

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.