Therapie最新文献

Purpose: 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.

Objectives: 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.

Objectives: 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.

Methods: 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.

Results: 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 cycle for SC immunoglobulins. Following the onset of an infusion-related reaction, the infusion was most commonly discontinued (87.7%) or the infusion rate reduced (9.1%). In 64 cases, resolution of the reaction allowed the continuation of treatment with reduced infusion rates (65%), premedication (28%), or both (7%). Resumption of the infusion did not lead to recurrence in 60% of cases. For subsequent cycles, administration of the same formulation (n=100) resulted in recurrence in 40% of cases, while switching to a different formulation (n=16) was associated with recurrence in 75% of cases.

Conclusion: Infusion-related reactions to immunoglobulins most frequently present as flu-like syndromes or cardiovascular disturbances, which are typically resolved by reducing the infusion rate or discontinuing the infusion. Resumption of the infusion is feasible following resolution, using a reduced rate or premedication. The findings suggest that switching to a different formulation of the same administration route does not confer a practical advantage.

Introduction: Apalutamide is an oral androgen receptor pathway inhibitor used to treat non-metastatic castration-resistant prostate cancer at high risk of developing metastases. Skin toxicity of apalutamide is documented, including a few cases of lichenoid drug eruptions (LDE). The objective of our study is to qualitatively and quantitatively describe LDE associated with apalutamide using data from the French Pharmacovigilance Database (FPVD) and Vigibase.

Methods: FPVD and Vigibase were queried on August 5, 2024, for reports of LDE associated with apalutamide. Disproportionality analysis was performed using VigiBase®, calculating the reporting odds ratio (ROR) and Bayesian confidence propagation neural network information components (IC).

Results: Qualitatively, we identified and analyzed 16 cases of apalutamide related-LDE. The average age of male patients was 75 years. The median time to LDE onset was 4 months. Clinically, LDE presented as maculopapular rashes, lichenified aspects, lichen planus, lichenoid keratosis, and psoriasiform aspects. Management typically involved apalutamide discontinuation (81,2%) and corticosteroid therapy (56,2%), with favourable outcomes in 10 cases (62,5%). Quantitatively, disproportionality analysis showed significant ROR and IC for LDE and apalutamide (ROR 6.5, 95% CI 6.0-7.0; IC 2.4, IC025 1.6-3.3).

Conclusion: Skin rash and pruritus reactions are frequently observed with apalutamide, possibly because of its chemical structure. Our qualitative and quantitative analysis of LDE cases observed among apalutamide exposed patients support a safety signal. LDE generally resolved with topical corticosteroids, but often required the discontinuation of apalutamide. When faced with a LDE, clinicians should consider exposure to apalutamide as one of the potential causes.