Amantadine use in the French prospective NS-Park cohort.

OBJECTIVE: To assess amantadine use and associated factors in the patients with Parkinson's disease (PD). BACKGROUND: Immediate-release amantadine is approved for the treatment of PD and is largely used in clinical practice to treat "levodopa-induced dyskinesia (LIDs). Its use varies according to countries and PD stages. The prospective NS-Park cohort collects features of PD patients followed by 26 French PD Expert Centres. METHODS: Variables used for the analyses included demographics, motor and non-motor PD symptoms and motor complications [motor fluctuations (MFs), LIDs)], antiparkinsonian pharmacological classes and levodopa equivalent daily dose (LEDD). We evaluated: (i) prevalence of amantadine use and compared clinical features of amantadine users vs. non-users (cross-sectional analysis); (ii) factors associated with amantadine initiation (longitudinal analysis); (iii) amantadine effect on LIDs, MFs, apathy, impulse control disorders and freezing of gait (Fog) (longitudinal analysis). RESULTS: Amantadine use prevalence was 12.6% (1,585/12,542, median dose = 200 mg). Amantadine users were significantly younger, with longer and more severe PD symptoms, greater LEDD and more frequent use of device-aided/surgical treatment. Factors independently associated with amantadine initiation were younger age, longer PD duration, more frequent LIDs, MFs and FoG, higher LEDD and better cognitive function. 9 of the 658 patients on amantadine had stopped it at the following visit, after 12-18 months (1.3%). New users of amantadine presented a higher improvement in LIDs and MF compared to amantadine never users. CONCLUSIONS: About 12% of PD patients within the French NS-Park cohort used amantadine, mostly those with younger age and more severe PD. Amantadine initiation was associated with a subsequent reduction in LIDs and MFs.

Differences in the location of bleeding with direct oral anticoagulants vs. vitamin K antagonists: A study in the World Health Organization's pharmacovigilance database.

AIMS: Clinical trials have found differences in bleeding locations between direct oral anticoagulants (DOAC) and vitamin K antagonists (VKA). The present study was performed to investigate these differences in real life using reports of adverse drug reactions registered in the World Health Organization's pharmacovigilance database, VigiBase®. METHODS: All bleeding registered between 1 January 2008 and 31 December 2021 in adults were included. The main objective was to compare bleeding locations reported with DOAC with those with VKA. As a secondary objective, we performed the same comparison with Xa vs. thrombin inhibitors. Results were presented as reporting odds ratios (RORs) adjusted on age, gender, origin of reports and co-medications with their 95% confidence interval. RESULTS: During this 14-year period, 142 228 instances of bleeding were registered with oral anticoagulants, including 39 570 with VKA and 102 658 with DOAC. Mean time to event was lower with DOAC (7.6 months) than with VKA (29.9 months) (P < .001). Significant differences in bleeding locations were found in the reports with less cerebral, urologic and nasal bleeding, more gynaecologic bleeding with DOAC than with VKA, without any significant differences in digestive and cutaneous locations. A higher risk of bleeding reports was found with Xa inhibitors vs. dabigatran whatever the locations (except digestive bleeding). CONCLUSION: This real-life study shows that the differences in bleeding locations between DOAC and VKA are not limited to the brain or gastrointestinal tracts. Significant differences were also found between Xa and thrombin inhibitors.

Effects of sociodemographic and player characteristics on baseline cognitive performance in 1000 rugby players: A retrospective 8-year follow-up study.

OBJECTIVES: To analyze the effects of sociodemographic and player characteristics on the Sport Concussion Assessment Tool and neuropsychological scores over 8 years in a large sample of rugby players. DESIGN: An 8-year retrospective study of preseason clinical assessments of professional rugby players and players enrolled in training academies at professional clubs. METHODS: The Sport Concussion Assessment Tool-3 or -5, Trail Making Test and Digit Symbol Substitution Test were administered prior to the start of the competition season for each player. Statistical analyses included: (i) descriptive analyses of sociodemographic, player and neuropsychological characteristics; (ii) multivariate models to identify factors influencing cognitive scores at the first visit; and (iii) linear mixed models to assess the evolution of the scores over the years. RESULTS: One thousand players were included (mean age: 22.8, males: 92 %). Twenty-two percent of the athletes reported baseline symptoms. A higher level of education was associated with better cognitive scores at the first visit and over the years. Forwards had poorer processing speed performances compared to backs at the first visit and over repeated assessments. Finally, the number of examinations was associated with improved cognitive scores showing a practice effect on all the neuropsychological tests, except for the Standardized Assessment of Concussion 5th edition. CONCLUSIONS: Results from this retrospective study could help to improve the management of athletes and return-to-play decision-making in collision sports.

Adverse drug reactions in pregnant women: Do they differ from those in non-pregnant women of childbearing age?

Pharmacoepidemiological research in pregnant women has focused on adverse drug reactions for the course of pregnancy or for the unborn child, but little is known on the risks for the mother. We reported the results of a study that compared adverse drug reactions in pregnant women with non-pregnant women of childbearing age, and investigated whether which types of adverse reactions were more often reported in pregnant women and which drugs were more often involved. This study was carried out in the French pharmacovigilance database (BNPV). We compared adverse drug reactions reported between 1 January 2010 and 31 December 2019 in pregnant women with those reported in of non-pregnant women of childbearing age. We cross-matched each pregnant woman with three non-pregnant women of childbearing age according to geographic area, age and year the adverse reaction was reported. Data analysis revealed that serious adverse reactions were more frequently reported in pregnant women, including anaphylactic reactions. Other adverse reactions including tachycardia, hypotension and hepatic injury were also more frequent in pregnant women than in non-pregnant women of the same age. This could be explained by physiological changes in pregnancy that lead to greater sensitivity to certain adverse reactions. Some drugs, such as phloroglucinol, metoclopramide, iron, atosiban and nifedipine, were more frequently involved in adverse reactions in pregnant women. These drugs are specifically used during pregnancy, which may explain why they are over-represented in adverse reactions. This is the first comparative descriptive study on drug adverse reactions in pregnant women. Specific epidemiological and pharmacokinetic studies are necessary to confirm these results and better understand the differences observed to improve the monitoring of pregnant women exposed to certain drugs.

UMSARS Versus Laryngoscopy-Based Assessment of Dysphagia.

Background: Multiple System Atrophy (MSA) dysphagia is routinely assessed by the Unified Multiple System Atrophy Rating Scale (UMSARS) part I-item 2. Objective: To compare the UMSARS part I-item 2 with an ear/nose/throat (ENT) expert physician assessment. Methods: We retrospectively analyzed the data of MSA patients who underwent an ENT assessment (nasofibroscopic and radioscopic exam) and an annual UMSARS assessment. Deglutition Handicap Index (DHI) and pulmonary/nutrition complications were collected. Results: Seventy-five MSA patients were included. The ENT assessment revealed more severe dysphagia compared to the UMSARS part I-item 2 score (P = 0.003). A higher proportion of patients with impaired protective mechanisms showed severe UMSARS-based dysphagia (P = 0.005). Patients with choking and oral/pharyngeal transit defects and nutritional complications were equally distributed across UMSARS part I-item 2 scores. Worse UMSARS part I-item 2 scores had worse DHI scores. Conclusions: The UMSARS-based assessment of dysphagia does not capture key aspects of pharyngo-laryngeal dysfunction reflecting swallowing efficiency.

Diarrhea and angiotensin II receptor blockers: Is there any difference between the different drugs?

Diarrhea is an adverse drug reaction (ADR) widely reported with olmesartan, an angiotensin II receptor blocker (ARB). Isolated case reports described this ADR with other ARBs. The present study was performed to investigate if, among the different ARBs, some drugs are more at risk of diarrhea than others. Using VigiBase®, the WHO pharmacovigilance database, we performed a disproportionality analysis (case/noncase study). Cases were reports with the MedDRA PT term « diarrhea ¼ and noncases all other reports registered during the same period in Vigibase® from April 6, 1995 to December 31, 2020. After comparison of ARBs and angiotensin converting enzyme inhibitors (ACEIs), the main analysis was a comparison of the diarrhea reporting risk between each ARB and the seven other ARBs. Results are reported as reporting odds ratio (ROR) adjusted on age, gender, exposure to antihypertensive, and antidiabetic drugs with their 95% confidence interval. Among the 22,429,334 deduplicated reports registered in VigiBase® during the study period, 73,507 involved ARBs, including 2119 diarrhea. The reporting risk of diarrhea was higher with ARBs than with ACEIs (ROR = 2.06 (1.55-2.17)). Diarrhea with ARBs mainly occurred in females with a mean age of 65 years. After exclusion of olmesartan (to minimize a notoriety bias), two ARBs were significantly associated with diarrhea: eprosartan (ROR = 1.93 (1.32-2.72) and telmisartan (ROR = 1.41 (1.23-1.62) but not the six others. The present study found first that diarrhea is more frequently reported with ARBs than with ACEIs and second that the risk of diarrhea differs according to the different ARBs. Diarrhea with ARBs is not a class effect.

Diarrhoea with the angiotensin receptor neprilysin inhibitor sacubitril + valsartan: A pharmacovigilance study.

Diarrhoea is an adverse drug reaction of the angiotensin receptor neprilysin inhibitor (ARNI) sacubitril + valsartan. It was also described with olmesartan and more recently with other angiotensin receptor blockers. The study was performed to compare diarrhoea reports in pharmacovigilance databases with sacubitril + valsartan and valsartan. The study used reports of diarrhoea with the ARNI sacubitril + valsartan registered: first in the French PharmacoVigilance Database (FPVD) and second in Vigibase®, the WHO Global Individual Case Safety Report database. After description of the main characteristics, disproportionality analyses were performed. Results are reported as reporting odds ratios (ROR) with 95% confidence interval. We found 29 reports of diarrhoea with sacubitril + valsartan in the FPVD and 686 in Vigibase®. With sacubitril + valsartan, diarrhoea occurred more frequently in males around 70 years with a median delay of 3 days. With valsartan, diarrhoea occurred more frequently in females around 68 years with a median delay of 0.5 days. In the FPVD, a significant association was found with sacubitril + valsartan in comparison with valsartan alone before (ROR = 8.78 [5.19-14.85]) and after (ROR = 11.19 [5.89-21.25]) exclusion of concomitant drugs known to be associated with diarrhoea. A significant association was also found in Vigibase® after adjustment on age, sex, reporter and its location (ROR = 1.31 [1.14-1.50]). Diarrhoea reported with sacubitril + valsartan has marked differences in gender, delay of occurrence and frequency of reporting in comparison with diarrhoea with valsartan. From a pharmacodynamic point of view, these results suggest a specific role of sacubitril in diarrhoea.