Clinical characteristics of a large cohort of patients with narcolepsy candidate for pitolisant: a cross-sectional study from the Italian PASS Wakix® Cohort.

INTRODUCTION: Narcolepsy is a chronic and rare hypersomnia of central origin characterized by excessive daytime sleepiness and a complex array of symptoms as well as by several medical comorbidities. With growing pharmacological options, polytherapy may increase the possibility of a patient-centered management of narcolepsy symptoms. The aims of our study are to describe a large cohort of Italian patients with narcolepsy who were candidates for pitolisant treatment and to compare patients' subgroups based on current drug prescription (drug-naïve patients in whom pitolisant was the first-choice treatment, switching to pitolisant from other monotherapy treatments, and adding on in polytherapy). METHODS: We conducted a cross-sectional survey based on Italian data from the inclusion visits of the Post Authorization Safety Study of pitolisant, a 5-year observational, multicenter, international study. RESULTS: One hundred ninety-one patients were enrolled (76.4% with narcolepsy type 1 and 23.6% with narcolepsy type 2). Most patients (63.4%) presented at least one comorbidity, mainly cardiovascular and psychiatric. Pitolisant was prescribed as an add-on treatment in 120/191 patients (62.8%), as switch from other therapies in 42/191 (22.0%), and as a first-line treatment in 29/191 (15.2%). Drug-naive patients presented more severe sleepiness, lower functional status, and a higher incidence of depressive symptoms. CONCLUSION: Our study presents the picture of a large cohort of Italian patients with narcolepsy who were prescribed with pitolisant, suggesting that polytherapy is highly frequent to tailor a patient-centered approach.

Glandular trichomes and essential oils in developing peppermint leaves: I. Variation of peltate trichome number and terpene distribution within leaves.

The trichome number and the variability in mono and sequisterpene distribution of peltate trichomes within a leaf was investigated during development of peppermint (Mentha×piperita L.) leaves. A larger number of peltate trichomes was initiated on adaxial epidermises than abaxial epidermises, but during leaf development a greater gland number was produced on abaxial epidermises. Evidence showed that the trichome number was not fixed at the time of leaf emergence. On both epidermises, the trichome distribution was found to change with its position on the leaf. A striking monoterpene composition variability was present among individual trichomes and between different parts of the leaf. Different rates of peltate trichome development and distribution as well as significant differences in trichome number and density were found between the epidermises. A clear and opposite trend was found between menthone and menthol percentages during development. Menthone and menthol were also found to be present in larger amounts on adaxial epidermises, whereas neomenthol and isomenthol had highest percentages on abaxial epidermises. Of the total oil collected from peltate trichomes, 60%, was composed of menthone. isomenthol, menthol and neomenthol and of the remaining 40 %, more than half was represented by other mono and sesquiterpenes while the final percentage was made up of a few unidentified early eluting compounds of high Volatility.