Quality of life and phonatory and morphological outcomes in cognitively unimpaired adolescents with Pierre Robin sequence: a cross-sectional study of 72 patients.

BACKGROUND: Pierre Robin sequence (PRS) is a heterogeneous condition involving retro(micro)gnathia, glossoptosis and upper airway obstruction, very often with posterior cleft palate. Patients with PRS, either isolated or associated with Stickler syndrome have good intellectual prognosis. Nevertheless, the quality of life in adolescence and the phonatory and morphological outcomes are rarely analysed. We assessed the phonatory and morphological outcomes of 72 cognitively unimpaired adolescents with PRS, studied their oral (COHIP-SF19), vocal (VHI-9i) and generic quality of life (QoL; KIDSCREEN-52), and searched for determinants of these outcomes. RESULTS: Two-thirds of our adolescents retained low or moderate phonation difficulties, but risk factors were not identified. For 14%, morphological results were considered disharmonious, with no link to neonatal retrognathia severity. Only one vs two-stage surgery seemed to affect final aesthetic results. The oral QoL of these adolescents was comparable to that of control patients and was significantly better than that of children with other craniofacial malformations (COHIP-SF19 = 17.5, 15.4 and 25.7, respectively). The oral QoL of the adolescents with non-isolated PRS was significantly worse (COHIP-SF19 = 24.2) than that of control patients and close to that of children with other craniofacial malformations. The vocal QoL of the adolescents (mean [SD] VHI-9i = 7.5 [5.4]) was better than that of patients with other voice pathologies and better when phonation was good. The generic QoL of the adolescents was satisfactory but slightly lower than that of controls, especially in dimensions concerning physical well-being, relationships and autonomy. QoL results were lower for adolescents with non-isolated than isolated PRS. Only non-isolated PRS and low oral QoL affected generic QoL. CONCLUSION: Morphological or phonatory impairments remain non-rare in adolescents with PRS but do not seem to be directly responsible for altered QoL. These adolescents, especially those with non-isolated PRS, show self-confidence and social-relation fragility. We must focus on long-term functional and psychological results for PRS patients and improve therapy protocols and follow-up, notably those affecting the oral aspects of the disease.

Evaluation of the effects of therapeutic and supratherapeutic doses of agomelatine on the QT/QTc interval: a phase I, randomized, double-blind, placebo-controlled and positive-controlled, crossover thorough QT/QTc study conducted in healthy volunteers.

: The effects of the antidepressant agomelatine up to a supratherapeutic dose (400 mg, single dose) on the QT corrected (QTc) interval were assessed in a randomized, double-blind, placebo- and positive-controlled, crossover thorough QT/QTc study in young healthy volunteers (29 males and 31 females). The primary criterion was the study of male or female population-derived QT-corrected interval (QTcP). The main analysis on the QTcP demonstrated that among the 10 postdose measurement times planned, the largest 1-sided 95% confidence interval upper bound of the difference between agomelatine 50 mg and placebo-adjusted means, and 1 of the differences between agomelatine 400 mg and placebo-adjusted means were both strictly inferior to the 10 millisecond upper-bound threshold of regulatory concern. The assay sensitivity was established with the positive control moxifloxacin (400 mg) and detected an effect on the mean QTcP interval that is around the threshold of regulatory concern (5 milliseconds). No relationship between QTcP and plasma concentrations of agomelatine was observed. In conclusion, agomelatine up to 400 mg has no effect on the QTc interval as demonstrated in the present regulatory thorough QT/QTc study.