<div><h3>Introduction</h3><div>Les opioïdes sont des médicaments essentiels, cependant, leur consommation s’accompagne de risques. Le programme POP « Prévention et réduction des risques des surdoses liées aux opioïdes en région PACA » vise à améliorer la prise en charge des patients à risque de surdose et la diffusion de naloxone. Nous avons réalisé un état des lieux auprès de pharmaciens dont l’objectif était d’évaluer leurs connaissances, pratiques, difficultés et besoins concernant la prise en charge des patients utilisateurs d’opioïdes et la prévention des surdoses et de leur proposer des supports d’information adaptés à leurs besoins.</div></div><div><h3>Matériels et méthodes</h3><div>Dans le cadre du programme POP, des pharmaciens ont été sollicités via un questionnaire en ligne (février–mars 2024) et entretiens semi-directifs (avril 2024).</div></div><div><h3>Résultat</h3><div>Au total, 107 pharmaciens ont répondu au questionnaire et 10 ont participé aux entretiens. Soixante-quatorze pour cent ont indiqué avoir été confrontés à des patients présentant un trouble de l’usage d’un médicament opioïde. L’échelle de repérage <em>Prescription Opioid Misuse Index</em> est peu connue (92 %). Seuls 37 % des pharmaciens déclaraient avoir connaissance de la disponibilité de naloxone prête à l’emploi et 87 % ne se sentent pas à l’aise avec les conseils associés à sa dispensation. Les actions en cas de mésusage incluent un contact avec le prescripteur (76 %), un refus de dispensation (76 %), une dispensation adaptée ou fractionnée (60 %). Concernant les besoins, 95 % étaient intéressés par une formation, 44 % par des outils pratiques, et 41 % par des documents à destination des patients. À partir des besoins exprimés, des actions d’information et d’aller vers ont été réalisées.</div></div><div><h3>Conclusion</h3><div>Les résultats soulignent la nécessité d’améliorer les connaissances des pharmaciens sur le risque de surdose et la naloxone. Il est essentiel de proposer régulièrement des formations et de diffuser des outils pratiques.</div></div><div><h3>Introduction</h3><div>Opioids are essential medicines, but their use is associated with risks. The POP program “Prevention and risk reduction of Opioid-related overdoses in the PACA region” aims to improve the management of patients at risk of overdose and the distribution of naloxone. We have conducted a survey of pharmacist with the aim was to assess their knowledge, practices, difficulties and needs concerning the management of opioid users and overdose prevention and naloxone diffusion, and to propose training materials adapted to their needs.</div></div><div><h3>Materials and methods</h3><div>In the context of POP programme, pharmacists were approached via an online questionnaire (February–March 2024) and semi-structured interviews (April 2024).</div></div><div><h3>Results</h3><div>A total of 107 pharmacists completed the questionnaire and 10 took part in the interviews. Seventy-four per cent said th
{"title":"Prévention du mésusage et du risque des surdoses d’opioïdes et diffusion de naloxone : état des lieux des pratiques, besoins et perspectives auprès des pharmaciens d’officine","authors":"Armelle Chan Soc Foh , Salim Mezaache , Franck Turlure , Nathalie Fredon , Stéphane Pichon , Laurent Peillard , Joelle Micallef , Elisabeth Frauger","doi":"10.1016/j.therap.2025.02.006","DOIUrl":"10.1016/j.therap.2025.02.006","url":null,"abstract":"<div><h3>Introduction</h3><div>Les opioïdes sont des médicaments essentiels, cependant, leur consommation s’accompagne de risques. Le programme POP « Prévention et réduction des risques des surdoses liées aux opioïdes en région PACA » vise à améliorer la prise en charge des patients à risque de surdose et la diffusion de naloxone. Nous avons réalisé un état des lieux auprès de pharmaciens dont l’objectif était d’évaluer leurs connaissances, pratiques, difficultés et besoins concernant la prise en charge des patients utilisateurs d’opioïdes et la prévention des surdoses et de leur proposer des supports d’information adaptés à leurs besoins.</div></div><div><h3>Matériels et méthodes</h3><div>Dans le cadre du programme POP, des pharmaciens ont été sollicités via un questionnaire en ligne (février–mars 2024) et entretiens semi-directifs (avril 2024).</div></div><div><h3>Résultat</h3><div>Au total, 107 pharmaciens ont répondu au questionnaire et 10 ont participé aux entretiens. Soixante-quatorze pour cent ont indiqué avoir été confrontés à des patients présentant un trouble de l’usage d’un médicament opioïde. L’échelle de repérage <em>Prescription Opioid Misuse Index</em> est peu connue (92 %). Seuls 37 % des pharmaciens déclaraient avoir connaissance de la disponibilité de naloxone prête à l’emploi et 87 % ne se sentent pas à l’aise avec les conseils associés à sa dispensation. Les actions en cas de mésusage incluent un contact avec le prescripteur (76 %), un refus de dispensation (76 %), une dispensation adaptée ou fractionnée (60 %). Concernant les besoins, 95 % étaient intéressés par une formation, 44 % par des outils pratiques, et 41 % par des documents à destination des patients. À partir des besoins exprimés, des actions d’information et d’aller vers ont été réalisées.</div></div><div><h3>Conclusion</h3><div>Les résultats soulignent la nécessité d’améliorer les connaissances des pharmaciens sur le risque de surdose et la naloxone. Il est essentiel de proposer régulièrement des formations et de diffuser des outils pratiques.</div></div><div><h3>Introduction</h3><div>Opioids are essential medicines, but their use is associated with risks. The POP program “Prevention and risk reduction of Opioid-related overdoses in the PACA region” aims to improve the management of patients at risk of overdose and the distribution of naloxone. We have conducted a survey of pharmacist with the aim was to assess their knowledge, practices, difficulties and needs concerning the management of opioid users and overdose prevention and naloxone diffusion, and to propose training materials adapted to their needs.</div></div><div><h3>Materials and methods</h3><div>In the context of POP programme, pharmacists were approached via an online questionnaire (February–March 2024) and semi-structured interviews (April 2024).</div></div><div><h3>Results</h3><div>A total of 107 pharmacists completed the questionnaire and 10 took part in the interviews. Seventy-four per cent said th","PeriodicalId":23147,"journal":{"name":"Therapie","volume":"80 5","pages":"Pages 507-518"},"PeriodicalIF":1.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670957","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}
To describe cardiovascular adverse reactions reported after intravitreal injections of vascular endothelial growth factor inhibitors (I-VEGF) as registered in the French Pharmacovigilance Database (FPVDB).
Methods
This retrospective study assessed spontaneous adverse drug reactions reported to the French pharmacovigilance system and registered in the FPVDB from April 2007 to June 2023. Eligible cases of thromboembolic events and arterial hypertension associated with three I-VEGFs (aflibercept, ranibizumab and bevacizumab) were selected.
Results
A total of 127 cases were included (83 for ranibizumab, 37 for aflibercept, and 7 for bevacizumab), including 21 cases of arterial hypertension and 106 cases of thromboembolic events. The median onset time for thromboembolic events ranged from 1 to 119 days following injection, and from 0 to 30 days for arterial hypertension. The median number of injections ranged from 1 to 24 before the occurrence of an adverse drug reaction. In 23% of cases, no risk factor was found for the occurrence of a cardiovascular or thromboembolic adverse event. In two cases, a positive rechallenge was documented.
Conclusion
The rational use of pharmacological data, some relevant spontaneous reports and some pharmacoepidemiological studies are a prompt to health professionals to take precautions in patients with risk factors requiring I-VEGF. However, European Summaries of Product Characteristics do not give a clear picture to healthcare professionals concerning the precautions to take for patients with risk factors.
{"title":"Intravitreal vascular endothelial growth factor inhibitors and cardiovascular adverse drug reactions: Added value of the data of the French pharmacovigilance spontaneous reporting assessment","authors":"Aurélie Bobet , Leila Chebane , Annie-Pierre Jonville-Bera , Marina Babin , Thomas Soeiro , Haleh Bagheri","doi":"10.1016/j.therap.2025.02.008","DOIUrl":"10.1016/j.therap.2025.02.008","url":null,"abstract":"<div><h3>Aim</h3><div><span><span>To describe cardiovascular adverse reactions reported after </span>intravitreal injections<span> of vascular endothelial growth factor inhibitors (I-VEGF) as registered in the French </span></span>Pharmacovigilance Database (FPVDB).</div></div><div><h3>Methods</h3><div>This retrospective study assessed spontaneous adverse drug reactions<span> reported to the French pharmacovigilance system and registered in the FPVDB from April 2007 to June 2023. Eligible cases of thromboembolic<span> events and arterial hypertension associated with three I-VEGFs (aflibercept, ranibizumab and bevacizumab) were selected.</span></span></div></div><div><h3>Results</h3><div><span>A total of 127 cases were included (83 for ranibizumab, 37 for aflibercept, and 7 for bevacizumab), including 21 cases of arterial hypertension and 106 cases of thromboembolic events. The median onset time for thromboembolic events ranged from 1 to 119</span> <!-->days following injection, and from 0 to 30<!--> <!-->days for arterial hypertension. The median number of injections ranged from 1 to 24 before the occurrence of an adverse drug reaction. In 23% of cases, no risk factor was found for the occurrence of a cardiovascular or thromboembolic adverse event. In two cases, a positive rechallenge was documented.</div></div><div><h3>Conclusion</h3><div>The rational use of pharmacological data, some relevant spontaneous reports and some pharmacoepidemiological studies are a prompt to health professionals to take precautions in patients with risk factors requiring I-VEGF. However, European Summaries of Product Characteristics do not give a clear picture to healthcare professionals concerning the precautions to take for patients with risk factors.</div></div>","PeriodicalId":23147,"journal":{"name":"Therapie","volume":"80 5","pages":"Pages 589-597"},"PeriodicalIF":1.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664491","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}
<div><h3>Objectifs</h3><div>Les réactions liées à la perfusion avec les immunoglobulines sont bien connues. L’objectif était de les caractériser à partir des données recueillies en vie réelle afin de fournir des informations utiles en pratique clinique.</div></div><div><h3>Méthodes</h3><div>Cette étude descriptive a analysé les cas de réaction aux perfusions issues de la base nationale de pharmacovigilance française concernant les immunoglobulines administrées par voie intraveineuse ou sous-cutanée jusqu’au 27 décembre 2023.</div></div><div><h3>Résultats</h3><div>Sur la période étudiée, 239 cas de réaction à la perfusion ont été rapportés, principalement avec des immunoglobulines intraveineuses (97,4 %). Dans un peu plus de la moitié des cas (51 %), les réactions à la perfusion se manifestaient par un syndrome pseudo-grippal. Elles se produisaient généralement lors de la première cure pour les immunoglobulines intraveineuses et de la quatrième pour les immunoglobulines sous-cutanées. Suite à la survenue d’une réaction à la perfusion, la perfusion était en majorité arrêtée (87,7 %) ou le débit était diminué (9,1 %). Pour 64 cas, la résolution de la réaction à la perfusion permettait de reprendre la cure avec une diminution du débit de perfusion (65 %), une prémédication (28 %) ou l’association des deux (7 %). La reprise de la cure n’engendrait pas de récurrence de la réaction à la perfusion dans 60 % des cas. Pour les cures suivantes, l’administration de la même spécialité (<em>n</em> <!-->=<!--> <!-->100) entraînait une récurrence dans 40 % des cas et pour un changement de spécialité (<em>n</em> <!-->=<!--> <!-->16) dans 75 % des cas.</div></div><div><h3>Conclusion</h3><div>Les réactions liées à la perfusion avec les immunoglobulines se manifestent le plus souvent par des syndromes pseudo-grippaux ou des troubles cardiovasculaires, résolutifs à la diminution de débit ou à l’arrêt. La reprise de la perfusion après résolution est possible avec un débit réduit ou une prémédication. Les résultats suggèrent qu’un changement de spécialité (de même voie d’administration) ne présente pas de bénéfice en pratique.</div></div><div><h3>Objectives</h3><div>Infusion-related reactions to immunoglobulins are well documented. The objective of this study was to characterize these reactions using real-world data to provide clinically relevant information.</div></div><div><h3>Methods</h3><div>This descriptive study analyzed cases of infusion-related reactions reported in the French National Pharmacovigilance Database for immunoglobulins administered via intravenous or subcutaneous routes up to December 27, 2023.</div></div><div><h3>Results</h3><div>During the study period, 239 cases of infusion-related reactions were reported, primarily associated with intravenous immunoglobulins (97.4%). In over half of the cases (51%), the reactions presented as flu-like syndromes. These reactions typically occurred during the first cycle for IV immunoglobulins and the fourth cycl
{"title":"Les réactions liées à la perfusion avec les immunoglobulines polyvalentes humaines : analyse de la base nationale de pharmacovigilance française","authors":"Aurélie Bobet , Justine Bravo , Eyrian Aubin-Beale , Blandine Bertin , François Montastruc , Romain Barus","doi":"10.1016/j.therap.2025.01.002","DOIUrl":"10.1016/j.therap.2025.01.002","url":null,"abstract":"<div><h3>Objectifs</h3><div>Les réactions liées à la perfusion avec les immunoglobulines sont bien connues. L’objectif était de les caractériser à partir des données recueillies en vie réelle afin de fournir des informations utiles en pratique clinique.</div></div><div><h3>Méthodes</h3><div>Cette étude descriptive a analysé les cas de réaction aux perfusions issues de la base nationale de pharmacovigilance française concernant les immunoglobulines administrées par voie intraveineuse ou sous-cutanée jusqu’au 27 décembre 2023.</div></div><div><h3>Résultats</h3><div>Sur la période étudiée, 239 cas de réaction à la perfusion ont été rapportés, principalement avec des immunoglobulines intraveineuses (97,4 %). Dans un peu plus de la moitié des cas (51 %), les réactions à la perfusion se manifestaient par un syndrome pseudo-grippal. Elles se produisaient généralement lors de la première cure pour les immunoglobulines intraveineuses et de la quatrième pour les immunoglobulines sous-cutanées. Suite à la survenue d’une réaction à la perfusion, la perfusion était en majorité arrêtée (87,7 %) ou le débit était diminué (9,1 %). Pour 64 cas, la résolution de la réaction à la perfusion permettait de reprendre la cure avec une diminution du débit de perfusion (65 %), une prémédication (28 %) ou l’association des deux (7 %). La reprise de la cure n’engendrait pas de récurrence de la réaction à la perfusion dans 60 % des cas. Pour les cures suivantes, l’administration de la même spécialité (<em>n</em> <!-->=<!--> <!-->100) entraînait une récurrence dans 40 % des cas et pour un changement de spécialité (<em>n</em> <!-->=<!--> <!-->16) dans 75 % des cas.</div></div><div><h3>Conclusion</h3><div>Les réactions liées à la perfusion avec les immunoglobulines se manifestent le plus souvent par des syndromes pseudo-grippaux ou des troubles cardiovasculaires, résolutifs à la diminution de débit ou à l’arrêt. La reprise de la perfusion après résolution est possible avec un débit réduit ou une prémédication. Les résultats suggèrent qu’un changement de spécialité (de même voie d’administration) ne présente pas de bénéfice en pratique.</div></div><div><h3>Objectives</h3><div>Infusion-related reactions to immunoglobulins are well documented. The objective of this study was to characterize these reactions using real-world data to provide clinically relevant information.</div></div><div><h3>Methods</h3><div>This descriptive study analyzed cases of infusion-related reactions reported in the French National Pharmacovigilance Database for immunoglobulins administered via intravenous or subcutaneous routes up to December 27, 2023.</div></div><div><h3>Results</h3><div>During the study period, 239 cases of infusion-related reactions were reported, primarily associated with intravenous immunoglobulins (97.4%). In over half of the cases (51%), the reactions presented as flu-like syndromes. These reactions typically occurred during the first cycle for IV immunoglobulins and the fourth cycl","PeriodicalId":23147,"journal":{"name":"Therapie","volume":"80 5","pages":"Pages 553-560"},"PeriodicalIF":1.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383365","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}
Candiduria, is becoming increasingly common among hospitalized and immunocompromised patients. This infection poses a therapeutic challenge due to the rise in fluconazole resistance among Candida species. When fluconazole is unsuitable due to resistance or drug interactions, amphotericin B (AmB) is recommended. However, AmB's systemic use is limited by nephrotoxicity, which has led to interest in intravesical (bladder-administered) AmB.
Methods
A retrospective study was conducted at Reims University Hospital on adult patients treated with intravesical AmB. Patient demographics, infection characteristics, and treatment details were extracted from medical records. Efficacy was determined by the absence of candiduria or rehospitalization, and renal safety was evaluated through serum creatinine and renal clearance before and after treatment. Adverse effects were graded by severity.
Results
Sixteen patients were included (10 female patients (62.5%), mean age 69.8 ± 15 years). Eight patients (50.0%) were admitted in urology department and diabetes mellitus was present in 9 patients (56.2%). Candida glabrata, resistant to fluconazole, was the most frequently isolated organism. Intravesical AmB was administered at a standard dose of 50 mg diluted in 1 liter of sterile water, delivered over 24 hours among almost all patients. Two patients were rehospitalized. Among patients with follow-up urine cultures, 66% (4 out of 6) achieved candiduria eradication. Two patients reported minor adverse effects, including mild catheter-related discomfort. No significant increase of serum creatinine level was observed after treatment.
Discussion and conclusion
Intravesical AmB appear effective and safe for treating fluconazole-resistant candiduria, especially in high-risk, elderly patients. While promising, these findings are based on a small sample, highlighting the need for larger studies with prospective design to further elucidate the optimal management strategies for candiduria in vulnerable patients.
{"title":"Evaluation of efficacy and tolerance of intravesical amphotericin B irrigation for the management of Candiduria","authors":"Zahoua Kartit , Maud Hulin , Dominique Hettler , Antoine Huguenin , Morgane Bonnet , Yohan N’Guyen","doi":"10.1016/j.therap.2025.02.010","DOIUrl":"10.1016/j.therap.2025.02.010","url":null,"abstract":"<div><h3>Introduction</h3><div><span><span>Candiduria, is becoming increasingly common among hospitalized and </span>immunocompromised patients<span>. This infection poses a therapeutic challenge due to the rise in fluconazole resistance among </span></span><em>Candida</em><span><span> species. When fluconazole is unsuitable due to resistance or drug interactions, </span>amphotericin B<span> (AmB) is recommended. However, AmB's systemic use is limited by nephrotoxicity, which has led to interest in intravesical (bladder-administered) AmB.</span></span></div></div><div><h3>Methods</h3><div><span><span>A retrospective study was conducted at Reims University Hospital on adult patients treated with intravesical AmB. Patient demographics, infection characteristics, and treatment details were extracted from medical records. Efficacy was determined by the </span>absence of candiduria or rehospitalization, and renal safety was evaluated through serum creatinine and </span>renal clearance<span> before and after treatment. Adverse effects were graded by severity.</span></div></div><div><h3>Results</h3><div>Sixteen patients were included (10 female patients (62.5%), mean age 69.8<!--> <!-->±<!--> <span>15 years). Eight patients (50.0%) were admitted in urology department and diabetes mellitus was present in 9 patients (56.2%). </span><span><em>Candida glabrata</em></span>, resistant to fluconazole, was the most frequently isolated organism. Intravesical AmB was administered at a standard dose of 50<!--> <!-->mg diluted in 1 liter of sterile water, delivered over 24<!--> <span>hours among almost all patients. Two patients were rehospitalized. Among patients with follow-up urine cultures, 66% (4 out of 6) achieved candiduria eradication. Two patients reported minor adverse effects, including mild catheter-related discomfort. No significant increase of serum creatinine level was observed after treatment.</span></div></div><div><h3>Discussion and conclusion</h3><div>Intravesical AmB appear effective and safe for treating fluconazole-resistant candiduria, especially in high-risk, elderly patients. While promising, these findings are based on a small sample, highlighting the need for larger studies with prospective design to further elucidate the optimal management strategies for candiduria in vulnerable patients.</div></div>","PeriodicalId":23147,"journal":{"name":"Therapie","volume":"80 5","pages":"Pages 598-606"},"PeriodicalIF":1.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744027","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}
This study has two main objectives: 1/ to validate the International Classification of Diseases, 10th revision (ICD-10) diagnostic codes of skin ulcer in one French hospital using medical charts; 2/ to validate an out-hospital algorithm against ICD-10 codes using a healthcare database.
Methods
We first validated in-hospital ICD-10 codes for pressure, diabetic and vascular skin ulcers using the Grenoble University Hospital medical charts. Secondly, we assessed the validity of an out-hospital algorithm using dressing reimbursements, medical exams and comorbidities to identify skin ulcers using the French “échantillon généraliste des benéficiaires” database. We then compared the type of skin ulcers in patients hospitalized 1 year around the out-hospital skin ulcer identification date. We calculated specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV).
Results
The performances of ICD-10 codes for identifying patients with vascular, diabetic and pressure ulcers were all superior to 70%. The out-hospital identification of skin ulcers selected very different patients, younger and with less comorbidities than those hospitalized for skin ulcers. In patients hospitalized 1 year before or after the first dispensation of wound dressings, the concordance with ICD-10 codes was modest. Indeed, patients are wrongly classified as pressure ulcers, vascular ulcers and diabetic foot ulcers in respectively 27.7%, 52.0% and 48.8% of skin ulcers.
Conclusion
We found that performances of the in-hospital identification of pressure, vascular and diabetic foot ulcers were high allowing to use them to conduct observational studies in healthcare databases. However, outpatient identification retrieved heterogeneous performance, we therefore advise researchers using the latter to perform a sensitivity analysis restricted to hospitalized patients.
{"title":"Validation of in-hospital diagnosis codes in one French hospital and out-hospital algorithm to identify skin ulcers in healthcare databases in France","authors":"Clément Jambon-Barbara , N’dah Mathieu Ouattara , Claire Bernardeau , Frédéric Olive , Sophie Blaise , Jean-Luc Cracowski , Charles Khouri","doi":"10.1016/j.therap.2025.02.003","DOIUrl":"10.1016/j.therap.2025.02.003","url":null,"abstract":"<div><h3>Purpose</h3><div>This study has two main objectives: 1/ to validate the International Classification of Diseases, 10th revision (ICD-10) diagnostic codes of skin ulcer in one French hospital using medical charts; 2/ to validate an out-hospital algorithm against ICD-10 codes using a healthcare database.</div></div><div><h3>Methods</h3><div>We first validated in-hospital ICD-10 codes for pressure, diabetic and vascular skin ulcers using the Grenoble University Hospital medical charts. Secondly, we assessed the validity of an out-hospital algorithm using dressing reimbursements, medical exams and comorbidities to identify skin ulcers using the French “<em>échantillon généraliste des benéficiaires</em>” database. We then compared the type of skin ulcers in patients hospitalized 1 year around the out-hospital skin ulcer identification date. We calculated specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV).</div></div><div><h3>Results</h3><div>The performances of ICD-10 codes for identifying patients with vascular, diabetic and pressure ulcers were all superior to 70%. The out-hospital identification of skin ulcers selected very different patients, younger and with less comorbidities than those hospitalized for skin ulcers. In patients hospitalized 1 year before or after the first dispensation of wound dressings, the concordance with ICD-10 codes was modest. Indeed, patients are wrongly classified as pressure ulcers, vascular ulcers and diabetic foot ulcers in respectively 27.7%, 52.0% and 48.8% of skin ulcers.</div></div><div><h3>Conclusion</h3><div>We found that performances of the in-hospital identification of pressure, vascular and diabetic foot ulcers were high allowing to use them to conduct observational studies in healthcare databases. However, outpatient identification retrieved heterogeneous performance, we therefore advise researchers using the latter to perform a sensitivity analysis restricted to hospitalized patients.</div></div>","PeriodicalId":23147,"journal":{"name":"Therapie","volume":"80 5","pages":"Pages 519-525"},"PeriodicalIF":1.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143504328","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}
Pub Date : 2025-09-01DOI: 10.1016/j.therap.2024.12.011
Emilien Ezine , Angélique Da Silva , Safa Idoudi , Céleste Lebbe , Basile Chrétien , Marion Sassier , Joachim Alexandre , Charles Dolladille
Importance
The safety profile of a rechallenge with BRAF inhibitors (BRAFi) or a combination of BRAF and MEK inhibitors (MEKi) following an adverse drug reaction (ADR) remains largely unexplored.
Objective
To identify the reported recurrence rate of the same ADR after a BRAFi ± MEKi targeted therapy (TT) rechallenge in patients with cancer and to identify factors associated with recurrence.
Design, setting, and participants
In this observational, pharmacovigilance study, ADR reports were sourced from VigiBase, the World Health Organization database. The inclusion criteria encompassed all BRAFi cases (with or without MEKi) through September 01, 2023, irrespective of the primary cancer diagnosis.
Main outcomes and measures
The primary outcome was the reported recurrence rate of the same initial ADR following TT rechallenge. Secondary outcomes measures included were identification of variables associated with recurrence among informative rechallenges, defined as those with known recurrence status.
Results
Out of 21,339 ADR cases linked to TT, 4771 (22.4%) reported a rechallenge, with 563 yielding informative data (11.8%). Recurrence of the initial ADR was reported in 223 cases, resulting in a reported recurrence rate of 39.6% (95% CI: 35.7–43.7). The highest recurrence rates in a rechallenge were observed for pyrexia (47%, 95% CI: 39–55), renal failure (46%, 95% CI: 32–60), and musculoskeletal disorders (44%, 95%CI: 33–56). There was no significant influence of factors such as TT regimen (either BRAFi monotherapy or any TT combination), age, sex, or the type of cancer on reported recurrence rate.
Conclusions and relevance
In real-world settings, approximately two-fifths of cases with notified TT rechallenges led to a reporting of recurrence of the same initial ADR. The primary determinant of reported recurrence seems to be the nature of the initial ADR rather than the TT regimen, or any other baseline patient characteristic.
{"title":"BRAF and MEK inhibitors rechallenge after an adverse drug reaction in patients with cancer: A pharmacovigilance cohort study","authors":"Emilien Ezine , Angélique Da Silva , Safa Idoudi , Céleste Lebbe , Basile Chrétien , Marion Sassier , Joachim Alexandre , Charles Dolladille","doi":"10.1016/j.therap.2024.12.011","DOIUrl":"10.1016/j.therap.2024.12.011","url":null,"abstract":"<div><h3>Importance</h3><div>The safety profile of a rechallenge with BRAF inhibitors (BRAFi) or a combination of BRAF and MEK inhibitors (MEKi) following an adverse drug reaction (ADR) remains largely unexplored.</div></div><div><h3>Objective</h3><div>To identify the reported recurrence rate of the same ADR after a BRAFi<!--> <!-->±<!--> <!-->MEKi targeted therapy (TT) rechallenge in patients with cancer and to identify factors associated with recurrence.</div></div><div><h3>Design, setting, and participants</h3><div>In this observational, pharmacovigilance study, ADR reports were sourced from VigiBase, the World Health Organization database. The inclusion criteria encompassed all BRAFi cases (with or without MEKi) through September 01, 2023, irrespective of the primary cancer diagnosis.</div></div><div><h3>Main outcomes and measures</h3><div>The primary outcome was the reported recurrence rate of the same initial ADR following TT rechallenge. Secondary outcomes measures included were identification of variables associated with recurrence among informative rechallenges, defined as those with known recurrence status.</div></div><div><h3>Results</h3><div>Out of 21,339 ADR cases linked to TT, 4771 (22.4%) reported a rechallenge, with 563 yielding informative data (11.8%). Recurrence of the initial ADR was reported in 223 cases, resulting in a reported recurrence rate of 39.6% (95% CI: 35.7–43.7). The highest recurrence rates in a rechallenge were observed for pyrexia (47%, 95% CI: 39–55), renal failure (46%, 95% CI: 32–60), and musculoskeletal disorders (44%, 95%CI: 33–56). There was no significant influence of factors such as TT regimen (either BRAFi monotherapy or any TT combination), age, sex, or the type of cancer on reported recurrence rate.</div></div><div><h3>Conclusions and relevance</h3><div>In real-world settings, approximately two-fifths of cases with notified TT rechallenges led to a reporting of recurrence of the same initial ADR. The primary determinant of reported recurrence seems to be the nature of the initial ADR rather than the TT regimen, or any other baseline patient characteristic.</div></div>","PeriodicalId":23147,"journal":{"name":"Therapie","volume":"80 5","pages":"Pages 526-535"},"PeriodicalIF":1.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041675","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}
Pub Date : 2025-09-01DOI: 10.1016/j.therap.2025.02.007
Marie Gligorov , Bénédicte Lebrun-Vignes , Kamel Masmoudi , Thierry Vial , Helga Junot , Valérie Pourcher , Sophie Demeret , Nicolas Weiss , Kevin Bihan
Aims
Guillain-Barré syndrome (GBS) is a rare autoimmune-mediated disease that can occur in a post-vaccination context. During the vaccination surveillance program of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, reports of GBS as a possible adverse effect (AE) of SARS-CoV-2 vaccines have been reported. Our aim was to describe post-vaccine reports of GBS whatever the vaccine used.
Methods
Data were obtained from the French pharmacovigilance database from inception (1 January 1985) to 1st March 2022. Reports were analyzed according to the French causality assessment method but only reports with a time to onset from the beginning of the treatment and the first symptoms occurrence of less than 4 weeks were included in our analysis, in accordance to the chronological criteria of the Brighton criteria.
Results
Three hundred and seventy-five (375) reports of GBS according to these selection criteria were retained for analysis. The data indicate a higher proportion of men (59%), with a median age of 54 years and a median time-to-onset after vaccination of 12 days. Around 45% of the reports were recorded with SARS-CoV-2 vaccines of which 68% involved post-mRNA vaccines and more precisely 56% post-tozinameran.
Conclusion
This study suggests that Guillain-Barré syndrome may be a rare but potentially severe adverse event that can occur in the first few weeks after vaccination whatever its nature. Even if a vaccine was injected in the weeks preceding the first signs of GBS, it is essential to perform a complete etiological assessment (search for bacterial or viral infection, particularly Campylobacter jejuni, etc.) in order to rule out another cause before considering its role in the onset of GBS. Continued pharmacovigilance survey of marketed vaccines is necessary to update or even harmonize its SmPCs.
{"title":"Vaccines and the risk of Guillain-Barré syndrome: A French pharmacovigilance analysis","authors":"Marie Gligorov , Bénédicte Lebrun-Vignes , Kamel Masmoudi , Thierry Vial , Helga Junot , Valérie Pourcher , Sophie Demeret , Nicolas Weiss , Kevin Bihan","doi":"10.1016/j.therap.2025.02.007","DOIUrl":"10.1016/j.therap.2025.02.007","url":null,"abstract":"<div><h3>Aims</h3><div>Guillain-Barré syndrome (GBS) is a rare autoimmune-mediated disease that can occur in a post-vaccination context. During the vaccination surveillance program of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, reports of GBS as a possible adverse effect (AE) of SARS-CoV-2 vaccines have been reported. Our aim was to describe post-vaccine reports of GBS whatever the vaccine used.</div></div><div><h3>Methods</h3><div>Data were obtained from the French pharmacovigilance database from inception (1 January 1985) to 1st March 2022. Reports were analyzed according to the French causality assessment method but only reports with a time to onset from the beginning of the treatment and the first symptoms occurrence of less than 4<!--> <!-->weeks were included in our analysis, in accordance to the chronological criteria of the Brighton criteria.</div></div><div><h3>Results</h3><div>Three hundred and seventy-five (375) reports of GBS according to these selection criteria were retained for analysis. The data indicate a higher proportion of men (59%), with a median age of 54<!--> <!-->years and a median time-to-onset after vaccination of 12<!--> <!-->days. Around 45% of the reports were recorded with SARS-CoV-2 vaccines of which 68% involved post-mRNA vaccines and more precisely 56% post-tozinameran.</div></div><div><h3>Conclusion</h3><div>This study suggests that Guillain-Barré syndrome may be a rare but potentially severe adverse event that can occur in the first few weeks after vaccination whatever its nature. Even if a vaccine was injected in the weeks preceding the first signs of GBS, it is essential to perform a complete etiological assessment (search for bacterial or viral infection, particularly <em>Campylobacter jejuni</em>, etc.) in order to rule out another cause before considering its role in the onset of GBS. Continued pharmacovigilance survey of marketed vaccines is necessary to update or even harmonize its SmPCs.</div></div>","PeriodicalId":23147,"journal":{"name":"Therapie","volume":"80 5","pages":"Pages 580-588"},"PeriodicalIF":1.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639828","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}
The objective is to investigate the association between antidepressant drugs intake and falls reporting, as well as the potential mediators in-between, in older adults.
Methods
In VigiBase®, the World Health Organization's pharmacovigilance database, we performed a disproportionality analysis to probe the putative associations between each antidepressant drugs class (non-selective monoamine reuptake inhibitors [NSMRIs], selective serotonin reuptake inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors [SNRIs], alpha-2-adrenergic receptor antagonists, and “other antidepressants”) and reports of falls in people aged 65 and over (NCT05628467). The reporting odds ratios and their 95% confidence interval were derived from logistic regression models with adjustment for confounders. We studied the falls-inducing mechanisms (delirium, hyponatremia, hypotension) by using causal mediation analyses and by using a disproportionality analysis for the co-occurrence of falls and these events.
Results
Our main analysis included 86,200 cases of falls reporting in older adults (of which 57% were 75 and over). A significant association was found between falls and every antidepressant drugs class, except for NSMRIs. According to causal mediation analysis, a direct effect on the falls reports was shown for alpha-2-adrenergic receptor antagonists and for “other antidepressants”. According to the co-reports analyses, all antidepressant drugs classes except SNRIs were associated with the co-event fall-delirium; SSRIs, alpha-2-adrenergic receptor antagonists, and “other antidepressants” with fall-hypotension; all antidepressant drugs classes except NSMRIs with fall-hyponatremia.
Conclusions
In multivariate disproportionality analyses, all antidepressant drugs classes were associated with signals of disproportionate reporting of falls in older adults, except for NSMRIs. In mediation analyses, a direct effect on the falls reports was only found for alpha-2-adrenergic receptor antagonists. Single-mediators based models seem insufficient to explain the diversity of clinical settings resulting in falls. These findings underline the necessity of a comprehensive analysis of all clinical and pharmacological features in older falling adults treated with antidepressant drugs.
{"title":"Association between antidepressant drugs and falls in older adults: A mediation analysis in the World Health Organization's pharmacovigilance database","authors":"Elise-Marie Minoc , Cédric Villain , Basile Chrétien , Soumia Benbrika , Marie Heraudeau , Claire Lafont , Clémence Béchade , Thierry Lobbedez , Véronique Lelong-Boulouard , Charles Dolladille","doi":"10.1016/j.therap.2025.01.004","DOIUrl":"10.1016/j.therap.2025.01.004","url":null,"abstract":"<div><h3>Objectives</h3><div>The objective is to investigate the association between antidepressant drugs intake and falls reporting, as well as the potential mediators in-between, in older adults.</div></div><div><h3>Methods</h3><div>In VigiBase®, the World Health Organization's pharmacovigilance database, we performed a disproportionality analysis to probe the putative associations between each antidepressant drugs class (non-selective monoamine reuptake inhibitors [NSMRIs], selective serotonin reuptake inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors [SNRIs], alpha-2-adrenergic receptor antagonists, and “other antidepressants”) and reports of falls in people aged 65 and over (<span><span>NCT05628467</span><svg><path></path></svg></span>). The reporting odds ratios and their 95% confidence interval were derived from logistic regression models with adjustment for confounders. We studied the falls-inducing mechanisms (delirium, hyponatremia, hypotension) by using causal mediation analyses and by using a disproportionality analysis for the co-occurrence of falls and these events.</div></div><div><h3>Results</h3><div>Our main analysis included 86,200 cases of falls reporting in older adults (of which 57% were 75 and over). A significant association was found between falls and every antidepressant drugs class, except for NSMRIs. According to causal mediation analysis, a direct effect on the falls reports was shown for alpha-2-adrenergic receptor antagonists and for “other antidepressants”. According to the co-reports analyses, all antidepressant drugs classes except SNRIs were associated with the co-event fall-delirium; SSRIs, alpha-2-adrenergic receptor antagonists, and “other antidepressants” with fall-hypotension; all antidepressant drugs classes except NSMRIs with fall-hyponatremia.</div></div><div><h3>Conclusions</h3><div>In multivariate disproportionality analyses, all antidepressant drugs classes were associated with signals of disproportionate reporting of falls in older adults, except for NSMRIs. In mediation analyses, a direct effect on the falls reports was only found for alpha-2-adrenergic receptor antagonists. Single-mediators based models seem insufficient to explain the diversity of clinical settings resulting in falls. These findings underline the necessity of a comprehensive analysis of all clinical and pharmacological features in older falling adults treated with antidepressant drugs.</div></div>","PeriodicalId":23147,"journal":{"name":"Therapie","volume":"80 5","pages":"Pages 561-571"},"PeriodicalIF":1.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558138","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}
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