In the 1990s, epidemiological studies estimated the prevalence of stroke caused by atrial fibrillation (AF) at about 15 %. Given the aging population, there is a rise in the number of AF patients. AF prevention guidelines based on clinical practice and the literature have been published and updated since 2001. Implementation seems to have an impact on the prescription of vitamin K antagonist (VKA). During the last 20 years, few population-based studies have focused on the prevalence of atrial arrhythmia (AA) in patients with stroke. The objective of the present prospective study, using data from 2008, was to evaluate the prevalence of AA (atrial fibrillation/flutter) in patients with stroke and the impact of implementing AF guidelines. The prevalence of AA was studied in patients diagnosed with stroke from January 1 to December 31, 2008 in the population-based Stroke Registry of Brest, France (total population, 363,760 according to the 2008 census, with 295,553 aged 15 years or older). Guidelines implementation was assessed in terms of antithrombotic therapy (VKA, antiplatelet agent, none), and the CHADS2 (Congestive heart failure, Hypertension, Age > 75 years, Diabetes mellitus, and prior Stroke or transient ischemic attack). 851 cases of stroke were identified. The prevalence of AA was 31.7 % (n = 264), and increased with age from < 20 % in patients aged 45 to 54 years to nearly 50 % in patients ≥ 85 years. In patients with AA, 231 strokes were ischemic, 28 hemorrhagic and 5 undetermined. At time of stroke, AA was known in 207 patients (78.4 %). 54 of the 152 patients with CHADS2 score ≥ 2 (35.5 %) were treated with VKA; this proportion decreased with age: 50 % between 50 and 74 years, 43.8 % between 75 and 84 years, and 25 % at 85 years and older. The prevalence of AA in the population-based Brest Stroke Registry in 2008 was higher than that reported by studies conducted 20 years ago. Despite publication of AF prevention guidelines, VKA prescription and use in elderly patients were significantly low.

Postpartum hemorrhage (PPH) is one of the leading causes of maternal morbidity worldwide. This study aimed to develop and validate a predictive model for PPH after vaginal deliveries, based on routinely available clinical and biological data. The derivation monocentric cohort included pregnant women with vaginal delivery at Brest University Hospital (France) between April 2013 and May 2015. Immediate PPH was defined as a blood loss of ≥500 mL in the first 24 h after delivery and measured with a graduated collector bag. A logistic model, using a combination of multiple imputation and variable selection with bootstrap, was used to construct a predictive model and a score for PPH. An external validation was performed on a prospective cohort of women who delivered between 2015 and 2019 at Brest University Hospital. Among 2742 deliveries, PPH occurred in 141 (5.1%) women. Eight factors were independently associated with PPH: pre-eclampsia (aOR 6.25, 95% CI 2.35–16.65), antepartum bleeding (aOR 2.36, 95% CI 1.43–3.91), multiple pregnancy (aOR 3.24, 95% CI 1.52–6.92), labor duration ≥ 8 h (aOR 1.81, 95% CI 1.20–2.73), macrosomia (aOR 2.33, 95% CI 1.36–4.00), episiotomy (aOR 2.02, 95% CI 1.40–2.93), platelet count < 150 Giga/L (aOR 2.59, 95% CI 1.47–4.55) and aPTT ratio ≥ 1.1 (aOR 2.01, 95% CI 1.25–3.23). The derived predictive score, ranging from 0 to 10 (woman at risk if score ≥ 1), demonstrated a good discriminant power (AUROC 0.69; 95% CI 0.65–0.74) and calibration. The external validation cohort was composed of 3061 vaginal deliveries. The predictive score on this independent cohort showed an acceptable ability to discriminate (AUROC 0.66; 95% CI 0.62–0.70). We derived and validated a robust predictive model identifying women at risk for PPH using in-depth statistical methodology. This score has the potential to improve the care of pregnant women and to take preventive actions on them.

Roscovitine (Seliciclib), a new protein kinase inhibitor, was administered orally to adult patients with cystic fibrosis for the first time in the ROSCO-CF trial, a dose-escalation, phase IIa, randomized, controlled trial. Extensive pharmacokinetic sampling was performed up to 12 h after the first oral dose. Roscovitine and its main metabolite M3 were quantified by liquid chromatography coupled with tandem mass spectrometry. The pharmacokinetics analyses were performed by non-linear mixed effects modelling. Monte Carlo simulations were performed to assess the impact of dose on the pharmacokinetics of oral roscovitine. Twenty-three patients received oral doses ranging from 200 to 800 mg of roscovitine and 138 data points were available for both roscovitine and M3 concentrations. The pharmacokinetics was best described by a two-compartment parent-metabolite model, with a complex saturable absorption process modelled as the sum of Gaussian inverse density functions. The Monte Carlo simulations showed a dose-dependent and saturable first-pass effect leading to pre-systemic formation of M3. The treatment with proton-pump inhibitors reduced the rate of absorption of oral roscovitine. The pharmacokinetics of oral roscovitine in adult patients with cystic fibrosis was non-linear and showed significant inter-individual variability. A repeat-dose study will be required to assess the inter-occasional variability of its pharmacokinetics.