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In this review, we outline the role of orexin receptor antagonists in disorders of sleep/wake and other potential neuropsychiatric conditions, with a focus on suvorexant, which is currently the only approved agent in this class. The efficacy of suvorexant was established in Phase 2-3 trials with treatment durations ranging from 1 to 12 months in patients with insomnia. Suvorexant is effective at improving sleep assessed by patient self-report and by polysomnography, with generally little effect on underlying sleep architecture. The main side-effect is next day somnolence. With the growing realization of the important connections between sleep and other disorders, studies are ongoing to explore this novel mechanism in other disorders such as Alzheimer's disease and depression.

The long-term survival of children with a central nervous system (CNS) tumour is improving. However, they experience late effects, including altered habits and patterns of sleep. We evaluated the presence and type of sleep disorders and daytime sleepiness in these children, and its associations with clinical characteristics and daily performance (fatigue and psychosocial functioning). In a cross-sectional study at the outpatient clinic of the Emma Children's Hospital AMC (February-June 2010), sleep, fatigue and psychosocial functioning were analysed in 31 CNS tumour patients (mean age: 11.8years; 20 boys) and compared with 78 patients treated for a non-CNS malignancy (mean age: 9.7years; 41 boys) and norm data. Questionnaires applied were the Sleep Disorder Scale for Children, the Epworth Sleepiness Scale, the Pediatric Quality of Life Inventory, and the Strengths and Difficulties Questionnaire. Sleeping habits and endocrine deficiencies were assessed with a self-developed questionnaire. Increased somnolence was found in CNS tumour patients compared with those with a non-CNS malignancy (8.8±2.8 versus 7.5±2.7; P

SUMMARY Study objectives were to determine the prevalence of sleepy driving accidents and to explore the factors associated with near-miss driving accidents and actual driving accidents in France. An epidemiological survey based on telephone interviews was conducted on a representative sample of French drivers. The questionnaire included sociodemographics, driving and sleep disorder items, and the Epworth sleepiness scale. Of 4774 drivers (response rate: 86%), 28% experienced at least one episode of severe sleepiness at the wheel (i.e. requiring to stop driving) in the previous year; 11% of drivers reported at least one near-miss accident in the previous year (46% sleep-related); 5.8% of drivers reported at least one accident, 5.2% of these being sleep related (an estimate of 90 000 sleep-related accidents per year in France). Sleepy driving accidents occurred more often in the city (53.8%), during short trips (84.6%) and during the day (84.6%). Using logistic regression, the best predictive factor for near-misses was the occurrence of at least one episode of severe sleepiness at the wheel in the past year [odds ratio (OR) 6.50, 95% confidence interval (CI), 5.20–8.12, P < 0.001]. The best predictive factors for accidents were being young (18–30 years; OR 2.13, 95% CI, 1.51– 3.00, P < 0.001) and experiencing at least one episode of severe sleepiness at the wheel (OR 2.03, 95% CI, 1.57–2.64, P < 0.001). Sleepiness at the wheel is a risk factor as important as age for traffic accidents. Near-misses are highly correlated to sleepiness at the wheel and should be considered as strong warning signals for future accidents.

Rate of recovery of daytime performance and sleepiness following moderate and severe sleep deprivation (SD) was examined when recovery opportunity was either augmented or restricted. Thirty healthy non-smokers, aged 18-33 years, participated in one of three conditions: moderate SD with augmented (9-h) recovery opportunities, moderate SD with restricted (6-h) recovery opportunities, or severe SD with augmented recovery opportunities. Each participant attended the laboratory for 8-9 consecutive nights: an adaptation and baseline night (23:00-08:00 hours), one or two night(s) of wakefulness, and five consecutive recovery sleep opportunities (23:00-08:00 hours or 02:00-08:00 hours). On each experimental day, psychomotor vigilance performance (PVT) and subjective sleepiness (SSS) were assessed at two-hourly intervals, and MSLTs were performed at 1000 h. PSG data was collected for each sleep period. For all groups, PVT performance significantly deteriorated during the period of wakefulness, and sleepiness significantly increased. Significant differences were observed between the groups during the recovery phase. Following moderate SD, response speed, lapses and SSS returned to baseline after one 9-h sleep opportunity, while sleep latencies required two 9-h opportunities. When the recovery opportunity was restricted to six hours, neither PVT performance nor sleepiness recovered, but stabilised at below-baseline levels. Following severe SD, sleepiness recovered after one (SSS) or two (physiological) 9-h sleep opportunities, however PVT performance remained significantly below baseline for the entire recovery period. These results suggest that the mechanisms underlying the recovery process may be more complicated than previously thought, and that we may have underestimated the impact of sleep loss and/or the restorative value of subsequent sleep.

Periodic Leg Movements (PLM) in sleep occur in a wide variety of sleep/wake disorders but their relationship with sleep disturbance, and notably with the concomitant existence of a 'restless legs' syndrome (RLS) remains unclear. We performed 24-h ambulatory polygraphy in a population of 54 consecutive, unselected patients with PLMs (Coleman's index greater than 5/h) who complained of different sleep disorders. A Principal Component Analysis (PCA) was conducted on seven variables from the sample, namely PLM index, patient's age, sleep stage changes per hour, sleep depth index (SWS+PS/TST), diurnal sleep time, number of awakenings exceeding 2 min and presence of a RLS. PCA yielded four independent factors. The PLM index and the changes of sleep stage clustered in a single factor, linking therefore sleep fragmentation to the frequency of PLMs. The second factor appeared to reflect a circadian sleep/wake disorder, combining diurnal sleep time with the number of long night awakenings. The third factor was mainly loaded by the patients' age and the sleep depth index, thus reflecting a well known relationship. Finally, the variable reflecting the existence of a RLS appeared isolated in a single factor, independent from the three previously described. These results confirm and extend the link between PLMs and sleep fragmentation, as well as the recently described dissociation between PLMs and diurnal somnolence. On the other hand, our analysis suggests that in PLM patients the concomitant existence of a RLS is not related to the frequency of occurrence of PLMs, at least when these latter are quantified independently of their arousal index.