Objectives: This analysis characterized changes in weight in participants with obstructive sleep apnea (OSA) or narcolepsy treated with solriamfetol (SunosiTM) 37.5 (OSA only), 75, 150, or 300 mg/d... Show moreObjectives: This analysis characterized changes in weight in participants with obstructive sleep apnea (OSA) or narcolepsy treated with solriamfetol (SunosiTM) 37.5 (OSA only), 75, 150, or 300 mg/d. Methods: In two 12-week, randomized, placebo-controlled trials and one 1-year open-label extension study, changes in weight were evaluated from baseline to end of study (week 12 or week 40 of the open -label extension [after up to 52 weeks of solriamfetol treatment]) in participants with OSA or narcolepsy. Results: After 12 weeks of solriamfetol treatment, median percent change in weight from baseline across all solriamfetol doses was-0.84%, compared with 0.54% for placebo, in participants with OSA; and-0.07%, compared with 3.08% for placebo, in participants with narcolepsy. After up to 52 weeks of solriamfetol treatment, overall median percent change in weight from baseline was-1.76%, which showed a dose-dependent pattern (75 mg, 0.57%; 150 mg,-1.2%; 300 mg,-2.5%).Results were similar in subgroups of participants with OSA or narcolepsy, with overall median percent changes in weight of-2.2% and-1.1%, respectively. After up to 52 weeks of solriamfetol treatment, the percentage of participants with weight loss >= 5% relative to baseline was 25.7% overall and increased in a dose -dependent manner (75 mg, 4.5%; 150 mg, 17.3%; 300 mg, 32.4%). Results were similar among sub-groups of participants with OSA or narcolepsy, with 26.4% and 24.2% of participants experiencing weight loss >= 5%, respectively. No weight-related treatment-emergent adverse events were serious. Conclusions: Solriamfetol treatment was associated with decreases in body weight in a dose-related manner.(c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Show less
In this thesis we describe the genetic, biochemical and clinical characteristics of patients with head and neck paragangliomas (HNPGL). In the Netherlands, the majority of SDHx mutation carriers,... Show moreIn this thesis we describe the genetic, biochemical and clinical characteristics of patients with head and neck paragangliomas (HNPGL). In the Netherlands, the majority of SDHx mutation carriers, harbor a mutation in the SDHD gene. Twenty-nine percent of patients with HNPGL have increased urinary excretion of 3-methoxytyramine, indicating dopaminergic activity. Test sensitivity of plasma 3MT measurement equals the measurement of urinary deconjugated 3MT excretion. Only a minority of HNPGL patients have increased plasma chromogranin A levels. Therefore, the practical implications of the measurement of plasma chromogranin A levels are limited in HNPGL patients. Patients screened for pheochromocytomas, because of a hereditary predisposition, present with less signs and symptoms, lower urinary excretion rates of catecholamines, and smaller tumors than patients presenting with symptomatic pheochromocytomas. Despite these differences in biochemical activity and the sizes of the tumors, there is no difference in patients regarding peri-operative complications. Patients with bilateral carotid body tumors are at risk for developing sleep disordered breathing. Sleep disordered breathing is associated with increased carotid body output, which is reflected by increased chemosensitivity. Show less