Sleep-related eating disorder (SRED) is a parasomnia with recurrent, involuntary, amnestic eating episodes during sleep. There is growing evidence of the association between SRED and medications. Therefore, we aimed to rank drugs showing the strongest association. VigiBase^® (WHO pharmacovigilance database) was queried for all reports of “Sleep-related eating disorder”. Disproportionality analysis relied on the Reporting Odds Ratio, with its 95% Confidence Interval (CI), and the Information Component. Our VigiBase^® query yielded 676 cases of drug-associated SRED. Reports mostly involved zolpidem (243, 35.9%), sodium oxybate (185, 27.4%), and quetiapine (97, 14.3%). Significant disproportionality was found for 35 medications, including zolpidem (387.6; 95%CI 331.2–453.7), sodium oxybate (204.2; 95%CI 172.4–241.8), suvorexant (67.3; 95%CI 38.0–119.2), quetiapine (53.3; 95%CI 43.0–66.1), and several psychostimulants and serotonin-norepinephrine reuptake inhibitors (SNRIs). Patients treated with nonbenzodiazepines or SNRIs were significantly older (mean age: 49.0 vs. 37.5; p < 0.001) and their SRED were more likely to be serious (62.6% vs. 51.4%; p = 0.014) than patients treated with sodium oxybate or psychostimulants. Psychotropic drugs are involved in almost all reports. In patients with SRED, an iatrogenic trigger should be searched for.

Aims: In medical education, the ability of large language models (LLMs) to match human performance raises questions about their potential as educational tools. This study evaluates LLMs' performance on Clinical Pharmacology and Therapeutics (CPT) exams, comparing their results to medical students and exploring their ability to identify poorly formulated multiple‐choice questions (MCQs).Methods: ChatGPT‐4 Omni, Gemini Advanced, Le Chat and DeepSeek R1 were tested on local CPT exams (third year of bachelor's degree, first/second year of master's degree) and the European Prescribing Exam (EuroPE⁺). The exams included MCQs and open‐ended questions assessing knowledge and prescribing skills. LLM results were analysed using the same scoring system as students. A confusion matrix was used to evaluate the ability of ChatGPT and Gemini to identify ambiguous/erroneous MCQs.Results: LLMs achieved comparable or superior results to medical students across all levels. For local exams, LLMs outperformed M1 students and matched L3 and M2 students. In EuroPE⁺, LLMs significantly outperformed students in both the knowledge and prescribing skills sections. All LLM errors in EuroPE⁺ were genuine (100%), whereas local exam errors were frequently due to ambiguities or correction flaws (24.3%). When both ChatGPT and Gemini provided the same incorrect answer to an MCQ, the specificity for detecting ambiguous questions was 92.9%, with a negative predictive value of 85.5%.Conclusion: LLMs demonstrate capabilities comparable to or exceeding medical students in CPT exams. Their ability to flag potentially flawed MCQs highlights their value not only as educational tools but also as quality control instruments in exam preparation.

A significant heterogeneity prevails in antipsychotics (APs) safety monitoring recommendations. Youths are deemed more vulnerable to cardiometabolic side effects. We aimed to assess age-dependent reporting of cardiac and metabolic disorders in youths, relying on the WHO safety database (VigiBase®). VigiBase® was queried for all reports of cardiac, glucose, lipid and nutritional disorders involving APs. Patients <18 years were classified as pediatric population. Disproportionality analyses relied on the Information Component (IC): the positivity of the lower end of its 95 % confidence interval was required to suspect a signal. We yielded 4,672 pediatric reports. In disproportionality analysis, nutritional disorders were leading in youths (IC 3.9 [3.9-4.0]). Among healthcare professionals' reports, stronger signals were detected in youths than in adults. Children had the greatest signal with nutritional disorders (IC 4.7 [4.6-4.8]). In adolescents, aripiprazole was ascribed to non-alcoholic steatohepatitis (NASH). Our findings, based on real-world data, support the hypothesis of a greater propensity for nutritional disorders in youths, despite limitations of pharmacovigilance studies. We suggest specific safety profiles, such as aripiprazole and NASH. Pending more answers from population-based studies, a careful anamnesis should seek for risk factors before AP initiation. A cautious monitoring is warranted to allow earlier identification of side effects.

Background: The World Health Organization recently described sudden sensorineural hearing loss (SSNHL) as a possible adverse effect of COVID-19 vaccines. Recent discordant pharmacoepidemiologic studies invite robust clinical investigations of SSNHL after COVID-19 messenger RNA (mRNA) vaccines. This postmarketing surveillance study, overseen by French public health authorities, is the first to clinically document postvaccination SSNHL and examine the role of potential risk factors. Objective: This nationwide study aimed to assess the relationship between SSNHL and exposure to mRNA COVID-19 vaccines and estimate the reporting rate (Rr) of SSNHL after mRNA vaccination per 1 million doses (primary outcome). Methods: We performed a retrospective review of all suspected cases of SSNHL after mRNA COVID-19 vaccination spontaneously reported in France between January 2021 and February 2022 based on a comprehensive medical evaluation, including the evaluation of patient medical history, side and range of hearing loss, and hearing recovery outcomes after a minimum period of 3 months. The quantification of hearing loss and assessment of hearing recovery outcomes were performed according to a grading system modified from the Siegel criteria. A cutoff of 21 days was used for the delay onset of SSNHL. The primary outcome was estimated using the total number of doses of each vaccine administered during the study period in France as the denominator. Results: From 400 extracted cases for tozinameran and elasomeran, 345 (86.3%) spontaneous reports were selected. After reviewing complementary data, 49.6% (171/345) of documented cases of SSNHL were identified. Of these, 83% (142/171) of SSNHL cases occurred after tozinameran vaccination: Rr=1.45/1,000,000 injections; no difference for the rank of injections; complete recovery in 22.5% (32/142) of cases; median delay onset before day 21=4 days (median age 51, IQR 13-83 years); and no effects of sex. A total of 16.9% (29/171) of SSNHL cases occurred after elasomeran vaccination: Rr=1.67/1,000,000 injections; rank effect in favor of the first injection (P=.03); complete recovery in 24% (7/29) of cases; median delay onset before day 21=8 days (median age 47, IQR 33-81 years); and no effects of sex. Autoimmune, cardiovascular, or audiovestibular risk factors were present in approximately 29.8% (51/171) of the cases. SSNHL was more often unilateral than bilateral for both mRNA vaccines (P<.001 for tozinameran; P<.003 for elasomeran). There were 13.5% (23/142) of cases of profound hearing loss, among which 74% (17/23) did not recover a serviceable ear. A positive rechallenge was documented for 8 cases. Conclusions: SSNHL after COVID-19 mRNA vaccines are very rare adverse events that do not call into question the benefits of mRNA vaccines but deserve to be known given the potentially disabling impact of sudden deafness. Therefore, it is essential to properly characterize postinjection SSNHL, especially in the case of a positive rechallenge, to provide appropriate individualized recommendations.

Antipsychotic drugs (APs) aim to treat schizophrenia, bipolar mania, and behavioral symptoms. In child psychiatry, despite limited evidence regarding their efficacy and safety, APs are increasingly subject to off-label use. Studies investigating addictology-related symptoms in young people being scarce, we aimed to characterize the different patterns of AP misuse and withdrawal in children and adolescents relying on the WHO pharmacovigilance database (VigiBase^®, Uppsala Monitoring Centre, Sweden). Using the standardized MedDRA Query ‘drug abuse, dependence and withdrawal’, disproportionality for each AP was assessed with the reporting odds ratio and the information component. A signal was detected when the lower end of the 95% confidence interval of the information component was positive. Results revealed mainly withdrawal symptoms in infants (under 2 years), intentional misuse in children (2 to 11 years), and abuse in adolescents (12 to 17 years). Olanzapine, risperidone, aripiprazole, and quetiapine were disproportionately reported in all age groups, with quetiapine being subject to a specific abuse signal in adolescents. Thus, in adolescents, the evocation of possible recreational consumption may lead to addiction-appropriate care. Further, in young patients with a history of AP treatment, a careful anamnesis may allow one to identify misuse and its role in the case of new-onset symptoms.

Background: The impact of pharmacokinetic variability of cabotegravir (CAB) and rilpivirine (RPV) long-acting (LA) injectable therapy on virological outcomes remains controversial. This study aimed to characterize the variability of CAB and RPV trough concentrations (Ctrough) and to identify the predictors of suboptimal exposure and virologic failure (VF) in a large real-world cohort. Methods: We conducted a multicenter observational study including people with human immunodeficiency virus type 1 (HIV-1) initiating LA-CAB/RPV as maintenance therapy from January to December 2022, in whom CAB and RPV plasma Ctrough were determined as part of therapeutic drug monitoring (TDM). Results: A total of 1674 CAB and 1687 RPV Ctrough measurements were collected from 736 people with HIV-1 (PWH). Significant interindividual variability in concentrations was observed. At month 1/month 3, 20%–30% of PWH had Ctrough <1120 ng/mL for CAB and 32 ng/mL for RPV. Predictors of lower Ctrough were body mass index (BMI) ≥30 kg/m2 and female sex at month 1, and only male sex at steady state. After a median follow-up of 12 (interquartile range, 9–16) months, VF occurred in 2.5% of PWH. At month 6 and month 12, VF was significantly associated with the presence of at least 2 risk factors (obesity, suboptimal Ctrough) (odds ratio [OR], 4.6, P = .047; OR, 5.15, P = .014), and CD4 nadir (OR, 0.56, P = .008; OR, 0.5, P = .001). Conclusions: Our large real-world study confirms significant variability in CAB and RPV exposure, with BMI and sex as key predictors of lower Ctrough. Suboptimal CAB and RPV Ctrough, particularly in people with obesity, increases the risk of VF during the first year of treatment, highlighting the usefulness of TDM in clinical practice.