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Over the last decades, general circulation model (GCM) simulations have been regularly evaluated in terms of their ability to reproduce the historical frequency of significantly recurrent weather patterns (WP) observed at the regional scale. Thus, a good simulation of the frequency of these particular WP by the GCM is generally conditioning the good representation of the regional statistics of surface variables such as temperature and precipitation. In this paper, the seasonal frequency of eight particular WP have been calculated using the daily geopotential height fields simulated by an ensemble of 26 Coupled Model Intercomparison Project Phase 5 (CMIP5) GCM. These WP are known as significantly influencing the French regional hydro‐climatology in terms of both frequency of low‐flows and high‐precipitation events. Four different bias correction methods have been applied on the simulated geopotential height fields before the calculation of the seasonal WP frequencies. The GCM ensemble showed overall good performances in terms of the simulation of WP seasonal frequencies. The application of a spatially and temporally non‐homogenous correction of simulated geopotential height fields improved significantly the simulation of WP frequencies for the four seasons. Finally, the evolution of the WP frequencies over the next century has been quantified. Three WP (WP2, WP4 and WP8) have pronounced seasonal changes, with WP2 and WP4 being less frequent in summer and autumn seasons, respectively, while WP8 being more frequent over spring, summer and autumn seasons. The strong simulated frequency evolution of WP2 and WP8 is an interesting result, which predicts the climate to be drier with time for France. Thus, WP2 (western oceanic circulation), grouping rainy days over the northern France region, is simulated as less frequent in future summers, while WP8 (anticyclonic situations), which groups non‐rainy days over France, is simulated as more frequent in future summers. [ABSTRACT FROM AUTHOR]

Purpose: To test bioequivalence of oral vitamin E formulations, water-soluble tocofersolan (test) and water-miscible (reference), in healthy adult volunteers, and their bioavailability in children with chronic cholestasis or cystic fibrosis. Methods: In a two-way open randomized single dose cross-over design, 1200 IU were administered in 12 healthy volunteers and 100 IU/kg in 12 children with chronic cholestasis or cystic fibrosis. Results: In healthy volunteers, formulations were not bioequivalent with a higher exposure to tocofersolan. In cholestatic children tocofersolan bioavailability was significantly higher than reference formulation (maximum plasma concentration: P = 0·008 and AUC: P = 0·0026). Bioavailability was not statistically different in cystic fibrosis. Conclusions: Oral tocofersolan was more bioavailable than the reference formulation in children with chronic cholestasis and similarly bioavailable in cystic fibrosis. Tocofersolan may represent an alternative to painful intramuscular vitamin E injections in chronic cholestasis, or to other oral formulations in cystic fibrosis. [ABSTRACT FROM AUTHOR]

Aims: In recent years, zolpidem has been the subject of numerous reports of misuse, abuse and dependence. In view of these risks, the French drug agency (ANSM) decreed in April 2017 the implementation of secure prescription pads. The objective of this study was to evaluate the impact of this regulatory measure on the prescription of zolpidem and other sedative medications (zopiclone, benzodiazepines and antihistamines) in long-term users of zolpidem and associated factors., Methods: We performed a historical cohort study using data from the Generalist Sample of Beneficiaries (EGB). All patients aged over 18 years old who were long-term users (at least 3 months) before the measure were enacted. We analysed the reimbursement trajectories of zolpidem, zopiclone, benzodiazepines and antihistamines (hydroxyzine and alimemazine) up to 2 years after the measure using a state sequence analysis., Results: Overall, 2502 patients were analysed. A four-cluster typology was identified: continuation of zolpidem (n = 1044, 42%), discontinuation of sedative medications (n = 766, 31%), change to zopiclone (n = 537, 21%) and change to hypnotic benzodiazepines (n = 155, 6%). The most frequently prescribed hypnotic benzodiazepine was lormetazepam. We identified age, sex, treatment for psychiatric or addictive disorder and volume of zolpidem use before the measure as factors associated with different reimbursement trajectories after the regulatory change., Conclusion: The regulatory change for zolpidem prescriptions reduced exposure to zolpidem among long-term users and also had a broad impact on prescriptions of other sedative medications. Switching to other medications that also present a potential risk of abuse or dependence should be carefully monitored., (© 2021 British Pharmacological Society.)