Therapie最新文献

{"title":"Digital pharmacological twins: Bridging multi-scale modelling and artificial intelligence for precision medicine: The DIGPHAT consortium.","authors":"Jean-Baptiste Woillard, Sébastien Benzekry, Julie Josse, Mélanie White-Koning, Etienne Chatelut, Emmanuelle Comets, Florian Lemaitre, Bénédicte Franck, Matthieu Gregoire, Françoise Stanke-Labesque, Sarah Zohar, Moreno Ursino, Christophe Battail","doi":"10.1016/j.therap.2025.09.006","DOIUrl":"https://doi.org/10.1016/j.therap.2025.09.006","url":null,"abstract":"<p><p>The advent of digital twins in pharmacology presents transformative potential for precision medicine, enabling personalized treatment optimization through dynamic computational simulations of drug interactions at molecular, cellular, and patient levels. These advanced virtual replicas of a patient's biological system are designed to predict individual therapeutic responses with high fidelity, thereby moving beyond the one-size-fits-all paradigm. This paper explores the concept of digital pharmacological twins, detailing how they can integrate heterogeneous data, including multi-omic, pharmacokinetic, pharmacodynamic, clinical, and environmental information, and employing a synergy of advanced mechanistic and machine learning models. Using illustrative examples from ongoing international initiatives, this work highlights the methodological frameworks necessary for developing and validating such comprehensive predictive tools. We underscore the critical importance of model interoperability, robust data integration strategies, and rigorous validation to ensure clinical utility. Ultimately, digital pharmacological twins promise to enhance therapeutic efficacy, minimize adverse drug reactions, and accelerate the translation of pharmacological science into tangible patient benefits.</p>","PeriodicalId":23147,"journal":{"name":"Therapie","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isolated depressive disorders and suicidality with finasteride use for androgenetic alopecia: A call for enhanced vigilance.","authors":"Hélène Géniaux, Marie-Laure Laroche","doi":"10.1016/j.therap.2025.09.004","DOIUrl":"https://doi.org/10.1016/j.therap.2025.09.004","url":null,"abstract":"<p><strong>Objective: </strong>To describe the clinical characteristics of depressive disorders and suicidality not associated with sexual dysfunction among users of finasteride 1mg/day for androgenetic alopecia.</p><p><strong>Methods: </strong>A retrospective descriptive analysis was conducted using data from the French National Pharmacovigilance Database (BNPV) from 1985 to May 2024. Cases were selected based on the presence of depressive or suicidal symptoms, classified in Medical Dictionary for Regulatory Activities (MedDRA) high-level group terms, with no co-reported sexual dysfunction.</p><p><strong>Results: </strong>Forty cases of depression or suicidality were identified in men treated with finasteride, with a median age of 31years. Most cases (62.5%) were classified as serious. In half of the cases, symptoms occurred within 9months of treatment initiation. Suicidality (ideation or attempts) was present in 40% of cases. Among patients who discontinued treatment, 45.2% reported symptom improvement. In unresolved cases (n=10), the median persistence of symptoms after withdrawal was 20.2months. A positive rechallenge was observed in two patients. Only 22.5% had a personal or family psychiatric history, and 17.5% reported a significant impact on quality of life.</p><p><strong>Conclusion: </strong>While adverse psychiatric drug reactions, including depressive symptoms and suicidality, are often reported in conjunction with sexual dysfunction, this study highlights the severity of depressive effects associated with finasteride, particularly the risk of suicidality even in the absence of associated sexual dysfunction or psychiatric history. The persistence of depressive symptoms sometimes beyond 20months post-discontinuation, underscores the need for adapted management and long-term monitoring. Finally, these findings highlight the need for thorough psychiatric evaluation at the time of prescription and ongoing suicide risk assessment throughout the course of treatment.</p>","PeriodicalId":23147,"journal":{"name":"Therapie","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145201336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fluoxetine-induced lower limb ecchymosis in an adolescent: A case report and literature review.","authors":"Thomas Darque, Clément Pruvot, Paul Nadin, Paola Sanchez-Pena, Myrtille Hamm, Juliette Miquel","doi":"10.1016/j.therap.2025.09.003","DOIUrl":"https://doi.org/10.1016/j.therap.2025.09.003","url":null,"abstract":"","PeriodicalId":23147,"journal":{"name":"Therapie","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145201361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progressive outer retinal necrosis complicating aseptic meningitis due to varicella zoster virus reactivation 44 days after infusion of natalizumab.","authors":"Hidaya Drissi Oudghiri, Thomas Ferreira De Moura, Brahim Azzouz, Catherine Feliu, Michael Hoang, Aurélie Brunet, Véronique Brodard, Yohan N'Guyen","doi":"10.1016/j.therap.2025.09.001","DOIUrl":"https://doi.org/10.1016/j.therap.2025.09.001","url":null,"abstract":"","PeriodicalId":23147,"journal":{"name":"Therapie","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Risk of mucocutaneous ulcerations associated with nicorandil: Recent data of the French Pharmacovigilance DataBase and Toulouse Hospital Discharge DataBase (NICORUC)].","authors":"Liliane Batty, Joanna Lapalus, Elsa Trime, Pauline Schiro, Romain Barus, Didier Fabre, Johana Béné, Julien Moragny, Viktoryia Prontskus, Haleh Bagheri","doi":"10.1016/j.therap.2025.08.001","DOIUrl":"https://doi.org/10.1016/j.therap.2025.08.001","url":null,"abstract":"<p><strong>Objective: </strong>The risk of mucocutaneous ulcerations associated with nicorandil remains a well-described adverse effect (AE). In case of a suspected AE, early diagnosis and immediate discontinuation of nicorandil are recommended. The aim of this study is to update pharmacovigilance data.</p><p><strong>Methods: </strong>Two sources of data were used for this study over the period from January 2017 to the end of November 2024: pharmacovigilance reports registered in the French PharmacoVigilance Database (FPVD) and data related to this AE and nicorandil extracted from the Toulouse hospital discharge database [programme de médicalisation des systèmes d'information (PMSI)].</p><p><strong>Results: </strong>We collected a total of 62 cases: 28 cases were registered in the FPVD and 34 additional cases could be identified in PMSI (n=62). None of these cases were reported to the Toulouse Pharmacovigilance Center. Patients were aged 56 to 97 years (sex-ratio 0.94). Nicorandil was discontinued for 36 patients (11 immediately). Six patients died, three of them despite nicorandil discontinuation, mainly due to digestive complications or sepsis. In 61% of FPVD cases (n=17) the AE was classified as severe. The median time to onset of the ulceration was 407 days (IQR: 123 to 1826 days). Cutaneous ulcerations were mainly localized on the lower limbs and mucosal ulcerations mainly affected the oral and digestive mucosa.</p><p><strong>Conclusion: </strong>Despite a decline in nicorandil sales since 2017 and several communications from the health authorities, our findings indicate the persistence of serious adverse reactions with nicorandil. Delayed discontinuation of the drug results in unnecessary investigations and potentially fatal outcomes. This study has shown that the PMSI and then the Clinical Data Warehouse (CDW), operational at the Toulouse Universitary Hospital Center since 18 June 2025, is a data source that contributes to reducing the under-reporting rate of unknown, albeit \"expected\" AE and to confirming the persistence of a validated pharmacovigilance signal.</p>","PeriodicalId":23147,"journal":{"name":"Therapie","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety of SARS-CoV-2 vaccination of pregnant women: Luxembourg's cohort study and literature review.","authors":"Victoria Ugolini, Nadine Petitpain, Didier Menzies, Dominique Swiegot, Audrey Fresse, Isabel De La Fuente Garcia, Anne-Cécile Vuillemin","doi":"10.1016/j.therap.2025.07.001","DOIUrl":"https://doi.org/10.1016/j.therap.2025.07.001","url":null,"abstract":"<p><strong>Aims of the study: </strong>European countries rapidly advised coronavirus disease 2019 (COVID-19) vaccination during pregnancy based on the evidence of first and reassuring data, especially with mRNA vaccines. Besides the close European pharmacovigilance monitoring, Luxembourg set up a prospective study cohort of women vaccinated during pregnancy to collect maternal and embryofetal outcomes.</p><p><strong>Methods: </strong>The study was conducted between June 2021 and October 2023, based on the national vaccination registry. Women were contacted by email and all reported events were retrospectively reviewed by an expert group.</p><p><strong>Results: </strong>The cohort involved 2335 vaccinated pregnant women of which 476 (20.4%) provided an answer, with 383 (80.5%) reporting no adverse events, 88 (18.5%) reporting a total of 90 adverse events (five reports not assessable). Vaccines were almost exclusively messenger RNA (mRNA) vaccines. Between the women who reported an adverse event and those who did not, no significant difference was identified for vaccine rank and pregnancy trimester. Among the 90 reported events, 73 (81,9%) were considered as without link with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination. Among the 17 adverse events having a non-excluded link with the vaccine, 16 (94%) had a favorable outcome and/or no pathophysiological explanation in regard to the vaccine. Rates of congenital anomalies and miscarriages were reassuringly lower than in the general population.</p><p><strong>Conclusion: </strong>Our Luxembourgish cohort study provided results consistent with other European pharmacovigilance surveys and literature data, in agreement with the overall safety of the vaccination against SARS-Cov-2 with mRNA vaccine during pregnancy.</p>","PeriodicalId":23147,"journal":{"name":"Therapie","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of urine drug screening on opioid agonist treatment maintenance with buprenorphine in primary care in France: A cluster-randomized trial.","authors":"Julie Dupouy, Vanessa Rousseau, Nicolas Authier, Paolo Di Patrizio, Gaetan Gentile, Valérie Gibaja, Catherine Laporte, Laurent Letrilliart, Christine Maynié, Joëlle Micallef, Michel Mallaret, Stéphane Oustric, Emilie Bérard, Maryse Lapeyre-Mestre","doi":"10.1016/j.therap.2025.07.003","DOIUrl":"https://doi.org/10.1016/j.therap.2025.07.003","url":null,"abstract":"<p><strong>Introduction: </strong>To assess the impact of onsite urine drug screening tests (OS-UDTs) in general practice compared with that of routine medical care on opioid agonist treatment (OAT) retention at six months in opioid-dependent patients initiating buprenorphine.</p><p><strong>Methods: </strong>In this cluster-randomized controlled trial, general practitioners (GPs) working in primary care and regularly managing patients treated with buprenorphine were invited to participate and were randomly assigned to the intervention or routine care group. GPs (cluster level) were asked to include 1-10 patients starting buprenorphine (individual level). The intervention included: (1) a training session on OS-UDTs; (2) the supply of OS-UDTs at GPs' offices; and (3) performing an OS-UDT before the first prescription of buprenorphine. The primary outcome was OAT retention at 6 months.</p><p><strong>Results: </strong>Among the 97 GPs included (intervention group: 49; control group: 48), 17 GPs included at least one patient, totaling 39 patients: 23 in the intervention group and 16 in the control group. Retention at 6 months was similar: 8 patients (34.7%) in the intervention group and 7 (43.8%) in the control group (OR=0.69 [95% CI: 0.18-2.56], P value=0.57). The patients were mainly men (69.2%), aged 39.3±11.6 years. All 13 patients in the intervention group who returned the acceptability questionnaire rated as \"normal medical practice\" the GP asking for OS-UDT for the management of OAT.</p><p><strong>Conclusion: </strong>In the context of a recent decline in the number of patients receiving OAT, and while all participating GPs reported regularly caring for patients for OUD, this inconclusive trial faced recruitment difficulties due to the low level of buprenorphine initiation in current daily practice. Nevertheless, this trial determined the characteristics of patients starting buprenorphine in primary care and revealed that OS-UDT was acceptable.</p><p><strong>Trial registration: </strong>NCT02345655.</p>","PeriodicalId":23147,"journal":{"name":"Therapie","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drugs associated with behavioral addictions: Real world analysis using the WHO pharmacovigilance database.","authors":"Louis Asselin, Edouard-Jules Laforgue, Mélanie Duval, Bruno Revol, Gwenaëlle Veyrac, Marie Grall-Bronnec, Caroline Victorri-Vigneau","doi":"10.1016/j.therap.2025.07.002","DOIUrl":"https://doi.org/10.1016/j.therap.2025.07.002","url":null,"abstract":"<p><strong>Objectives: </strong>Behavioral addictions (BA) are a newly recognized diagnostic entity. While some drugs are known to induce BA, some of them remains unknown. The aim of this study was to identify drugs for which B is not listed in the summaries of product characteristics.</p><p><strong>Methods: </strong>We conducted a search on Vigibase to identify health professional's cases where drugs are \"suspect\" coded with the following preferred terms: (1) 'behavioral addiction', (2) 'gambling disorder', (3) 'gaming disorder', (4) 'compulsive sexual behavior', (5) 'bulimia nervosa', (6) 'binge eating' and (7) 'compulsive shopping'. We selected drugs \"suspect\" in at least five cases for which the summaries of product characteristics do not mention BA. We applied a downward descriptive process (drug only suspect, positive dechallenge, well-documented cases) together with a disproportionality analysis and a PubMed search.</p><p><strong>Results: </strong>We identified 24 drugs across 7 pharmacological classes: antidepressants, antipsychotics, antiepileptics, benzodiazepines, psychostimulants, antidiabetics and retinoids. Olanzapine was the only accompanied by well-documented cases with positive dechallenges, exhibiting significant disproportionality analysis and associated with publications from the PubMed search.</p><p><strong>Conclusion: </strong>Our results highlights that several drugs and notably olanzapine are associated with BA. Further research using definitions enabling the diagnosis of addictive disorders for various BA is warranted.</p>","PeriodicalId":23147,"journal":{"name":"Therapie","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new tool to study the effects of in utero medication exposure on neurodevelopment in children.","authors":"Laurane Delteil, Caroline Hurault-Delarue, Catherine Arnaud, Dana Klapouszczak, Isabelle Lacroix, Malika Delobel-Ayoub","doi":"10.1016/j.therap.2025.06.009","DOIUrl":"https://doi.org/10.1016/j.therap.2025.06.009","url":null,"abstract":"<p><p>Here we describe the implementation of a new tool that would allow to assess the risk of serious disability following in utero exposure to medications. The overall objective was to enrich the EFEMERIS database [Évaluation chez la Femme Enceinte des MEdicaments et de leurs RISques (evaluation in the pregnant woman of medications and their risques database] containing data on reimbursed medication prescriptions and pregnancy outcomes) with data from the Haute-Garonne childhood disability registry (RHE31). The EFEMERIS database included 97,350 children born between 2004 and 2014 who were still living in Haute-Garonne at the age of 8. After matching with the RHE31, we identified 908 children (58.8% of RHE31-eligible children) with pervasive developmental disorder (PDD)/autism spectrum disorder (ASD) and/or severe motor impairment, severe neurosensory impairment or intellectual disability (IQ<50). Non-matched RHE31-eligible children did not differ significantly from matched children. Children diagnosed with PDD/ASD and/or severe disability were significantly more likely to have been exposed to certain ATC drug classes, particularly those in the \"nervous system\" class. Given the number of RHE31-children included, we can already envisage pharmacoepidemiologic studies to investigate the relationship between in utero medication exposure and the child's risk of neurodevelopmental disorders. This project, the first of its kind in France, will specifically improve data on the effects of medications on child neurodevelopment.</p>","PeriodicalId":23147,"journal":{"name":"Therapie","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Managing benzodiazepine withdrawal using prazepam substitution: Retrospective study of 86 patients].","authors":"Amir Kallab Debbih, Christophe Cutarella, Elisabeth Jouve, Michel Spadari, Joelle Micallef, Elisabeth Frauger","doi":"10.1016/j.therap.2025.06.008","DOIUrl":"https://doi.org/10.1016/j.therap.2025.06.008","url":null,"abstract":"<p><strong>Introduction: </strong>In France, the consumption of benzodiazepines (BZD) remains significant despite Haute autorité de santé (French National Authority of Health-HAS) recommendations. Various strategies are recommended: gradual dosage reduction of the BZD consumed or switch to diazepam in certain situations. Prazepam may also be an interesting molecule (long half-life, oral solution, less risk of abuse than diazepam). The aim of this study is to describe the efficacy, adverse events and feasibility of a BZD withdrawal program with prazepam.</p><p><strong>Materials and methods: </strong>Data were collected retrospectively among patients hospitalized at the Saint Barnabé clinic in 2022, which had a prescription of prazepam for withdrawal purposes. Withdrawal was considered successful at discharge if the initial prazepam dosage was reduced by more than 50 %, or if prazepam was stopped.</p><p><strong>Results: </strong>Most of the 86 patients had psychiatric or addictive comorbidities. Among them, 55 % had been using BZDs for over a year, 36 % consumed at least two BZDs, and 15 % took doses exceeding authorized indications. At discharge (median of 42 days), 29 % of patients were fully withdrawn, and 33 % had reduced their initial prazepam dosage by more than 50 %. The protocol was adapted in 38 % of patients, and 27 % experienced withdrawal symptoms. Several factors were significantly associated with partially successful or no success: presence of personality disorder, hospitalization in a context of cocaine use disorder, signs of withdrawal and protocol adaptation.</p><p><strong>Discussion: </strong>This study highlights the utility of prazepam in BZD withdrawal among a population at high risk for complicated withdrawal. The occurrence of clinical symptoms and protocol adjustments emphasize the importance of individualized management with regular medical reassessment.</p>","PeriodicalId":23147,"journal":{"name":"Therapie","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144733431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}