Therapie最新文献

Objective: In the general population, there has been a noticeable rise in the dispensing of gabapentinoids in recent years. The aim of this study was to provide an overview of all available data on the use and safety of gabapentinoids during pregnancy.

Methods: A systematic review was performed in PubMed and Reprotox using the search terms: "gabapentin", "pregabalin", "antiepileptic drugs" and terms associated with pregnancy. We included all studies in English that reported on the use and safety of gabapentin and pregabalin during pregnancy. We excluded abstracts, literature reviews, case reports and studies involving fewer than 5 exposures. Descriptive analyses and narrative syntheses were performed.

Results: A total of 27 high-quality studies were described. The prevalence of gabapentinoid use during pregnancy remained very low, at less than 1%. Five studies reported significant findings with increased risks of overall congenital anomalies, specific anomalies (nervous system, eyes, oro-facial clefs, urinary and genital system), miscarriage, stillbirth and specific neurodevelopmental outcomes after exposure to pregabalin during pregnancy. Concerning exposure to gabapentin, increased risks of preterm birth, preeclampsia, small-for-gestational-age and NICU admission were reported in two studies.

Conclusions: Prenatal exposure to pregabalin is associated with an increased risk of congenital anomalies and long-term neurodevelopmental outcomes while gabapentin exposure was associated with an increased risk of preeclampsia, preterm birth and small-for-gestational age. Larger studies are needed to confirm these data and explore additional outcomes. The combined evidence from this systematic review and animal studies raises concerns about the safety of using gabapentinoids during pregnancy. Careful evaluation of the benefit-risk balance for both mother and fetus/infant is essential when these medications cannot be avoided during pregnancy.

Aim: The long-acting buprenorphine Buvidal® is a recent type of opioid agonist treatment (OAT) used for opioid use disorder (OUD). It was initially suggested to preferentially use Buvidal® for specific OUD populations, including people in prison, or patients in recovery and on sublingual buprenorphine. We conducted a national study to examine whether the profile of patients treated with Buvidal® in France matched these initial recommendations.

Methods: A retrospective cross-sectional study was conducted in 13 national addiction centers (outside prison), using the individual medical records of patients initiated on Buvidal®. Baseline characteristics were collected and described, including sociodemographic features, comorbid medical conditions, concurrent substance use and prescription drug misuse, and OAT features before Buvidal® initiation, respectively.

Results: In total 101 patients (72.3% males, mean age 43.9±11.3years) were identified, which corresponded to one sixth of all patients treated with Buvidal® in France at the time of the study. Of them, 36 (36.4%) of them were professionally active, 35 (35.4%) were durably inactive, and the rest in an intermediary situation. Furthermore, 90 (90.0%) patients had at least one medical comorbidity (all types), and 83 (83.0%) at least one psychiatric comorbidity. Most frequent non-psychiatric comorbidities were chronic pain (n=20, 20.0%) and chronic viral infection (n=16, 17.8%). Current use of psychoactive substances included cocaine and crack (n=43, 42.6%), heroin (n=19, 18.8%), but also misuse of prescription drugs (n=20, 20%), mainly opioid analgesics. Moreover, 99 (98.0%) patients had an OAT before Buvidal® initiation, including 7 (8.1%) patients on methadone.

Conclusion: The profile of patients initiated on Buvidal® in France was extremely similar to that of patients treated for OUD in France, either in terms of social or clinical features. While initial recommendations essentially underlined the interest of Buvidal® for some niche populations, the on-the-ground practice reveals a more widespread use, including for unrecovered patients, or patients treated with methadone.

Objectives: Fluoropyrimidine-based therapies, 5-fluorouracil (5-FU) and its oral prodrugs, capecitabine and tegafur/oteracil/gimeracil (S-1), are pivotal drugs to treat gastric cancer. Fluoropyrimidines are associated with cardiotoxicity including ischemic cardiopathy. The mechanisms of ischemic cardiopathy are considered to be multifactorial, potentially involving metabolites of 5-FU generated by the dihydropyrimidine dehydrogenase (DPD). By using Vigibase®, the World Health Organization pharmacovigilance database, we aimed to investigate the implication of the 5-FU metabolites induced by DPD in the occurrence of ischemic cardiopathy in patients with gastric cancer using capecitabine.

Methods: In Vigibase®, we included serious reports of ischemic cardiopathy with capecitabine and S-1 from January 1st, 2013, to September 16th, 2023. Among patients with gastric cancer, we calculated the reporting odds ratio (ROR) of ischemic cardiopathy to compare capecitabine (a prodrug without DPD antagonist) with S-1 (a prodrug associated with a DPD antagonist). The ROR was also calculated regardless of the drug indication. An ancillary analysis based on the French pharmacovigilance database was also performed. We evaluated the ROR of serious cardiac disorders induced by 5-FU intravenous infusion according to the DPD status (no deficiency versus complete or partial deficiency).

Results: In gastric cancer, 1843 reports (including 23 ischemic cardiopathy) for capecitabine and 2225 reports (including 17 ischemic cardiopathy) for S-1 were included. Median time-to-onset was 7 (3-26) days for capecitabine and 22 (13.25-30) days for S-1. Capecitabine was associated with an increased ROR of ischemic cardiopathy compared with S-1 in gastric cancer (ROR=1.6; [95% CI=1.5-1.8]) and regardless of the indication (7.3; [95% CI=6.6-8.0]). In the ancillary analysis, among 5-FU users, the lack of DPD deficiency increased the ROR for cardiac disorders (2.1; [95% CI=1.9-2.3]) compared to the DPD deficiency.

Conclusion: This work supports the role of toxic 5-FU metabolites generated by dihydropyrimidine dehydrogenase in the occurrence of ischemic cardiopathy among patients with gastric cancer using capecitabine.

Background: By recovering data in an ordered manner and at the right time, clinical decision support systems (CDSSs) are designed to help healthcare professionals make decisions that improve patient care.

Objectives: The aim of the present study was to translate the REMEDI[e]s tool's explicit criteria, France's first reference list of potentially inappropriate drugs for the elderly, into seminatural language, in order to implement these criteria as alert rules and then enable their computer coding in a CDSS.

Methods: This work was carried out at Lille University Hospital by a team of clinical pharmacists with expertise in the use of pharmaceutical decision support systems, in collaboration with the authors of the REMEDI[e]s tool. A total of 3 multi-professional consensus meetings were required to discuss the construction of each rule in seminatural language and the coding choices.

Results: All REMEDIES criteria (n=104) were translated into seminatural language. This study is the first to have translated the 104 REMEDI[e]s explicit criteria into seminatural language.

Conclusions: One of the study's strengths relates to the close collaboration between the authors of the REMEDI[e]s tool and experts in CDSS programming rules; this ensured the exactitude of the seminatural language translations and limited (mis)interpretations.

Retinal vein occlusions and central retinal artery occlusions have been reported with coronavirus disease 2019 (COVID-19) vaccines. We aim to provide a descriptive analysis of cases reported in France until mid-2023, and recorded in the French pharmacovigilance database. An independent ophthalmologist reviewed all cases. We analyzed 290 cases (228 retinal vein occlusions, 58 central retinal artery occlusions, and four combinations). Retinal vein occlusions occurred with mRNA vaccines (68.0%) and adenovirus-vectored vaccines (32%), with an 11-day median onset delay. Almost half of the patients had retinal vein occlusion risk factors, mainly hypertension, and five had a positive rechallenge. Considering the lower adenovirus-vectored vaccines exposure in France, their proportion of retinal vein occlusions appears high. Among the 58 central retinal artery occlusion cases, most occurred with mRNA vaccines in patients with retinal artery occlusion risk factors (mainly hypertension), with a 17-day median onset delay. In conclusion, there was a temporal association in almost half of cases, but few cases with positive rechallenge, and many cases were confounded by risk factors (e.g., cardiovascular disorders, diabetes), which are also COVID-19 risk factors. Therefore, the risk of retinal vascular occlusion does not challenge the benefit-risk ratio of the vaccination, especially for mRNA vaccines.