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Sleep inertia, subjectively experienced as grogginess felt upon awakening, causes cognitive performance impairments that can require up to 1.5 hr to dissipate. It is unknown, however, how chronic sleep restriction (CSR) influences the magnitude and duration of sleep inertia-related performance deficits. Twenty-six healthy participants were enrolled in one of two in-laboratory sleep restriction protocols (one 32 day randomized control and one 38 day protocol) that separated the influence of sleep and circadian effects on performance using different \"day\"-lengths (20 and 42.85 hr day-lengths, respectively). The sleep opportunity per 24 hr day was the equivalent of 5.6 hr for each CSR condition and 8 hr for the Control condition. Participant's performance and subjective sleepiness were assessed within ~2 min after electroencephalogram-verified awakening and every 10 min thereafter for 70 min to evaluate performance and subjective sleepiness during sleep inertia. Performance within 2 min of awakening was ~10% worse in CSR conditions compared with Control and remained impaired across the dissipation of sleep inertia in the CSR conditions when compared with Control. These impairments in performance during sleep inertia occurred after only chronic exposure to sleep restriction and were even worse after awakenings during the biological nighttime. Interestingly, despite differences in objective performance, there were no significant differences between groups in subjective levels of sleepiness during sleep inertia. CSR worsens sleep inertia, especially for awakenings during the biological night. These findings are important for individuals needing to perform tasks quickly upon awakening, particularly those who obtain less than 6 hr of sleep on a nightly basis. The study \"Sleep Duration Required to Restore Performance During Chronic Sleep Restriction\" was registered as a clinical trial (#NCT01581125) at clinicaltrials.gov (https://clinicaltrials.gov/ct2/show/NCT01581125?term=NCT01581125.&rank=1).

Many adolescents are exposed to sleep restriction on school nights. We assessed how different apportionment of restricted sleep (continuous vs. split sleep) influences neurobehavioral function and glucose levels. Adolescents, aged 15-19 years, were evaluated in a dormitory setting using a parallel-group design. Following two baseline nights of 9-hour time-in-bed (TIB), participants underwent either 5 nights of continuous 6.5-h TIB (n = 29) or 5-hour nocturnal TIB with a 1.5-hour afternoon nap (n = 29). After two recovery nights of 9-hour TIB, participants were sleep restricted for another three nights. Sleep was assessed using polysomnography (PSG). Cognitive performance and mood were evaluated three times per day. Oral glucose tolerance tests (OGTT) were conducted on mornings after baseline sleep, recovery sleep, and the third day of each sleep restriction cycle. The split sleep group had fewer vigilance lapses, better working memory and executive function, faster processing speed, lower level of subjective sleepiness, and more positive mood, even though PSG-verified total sleep time was less than the continuous sleep group. However, vigilance in both sleep-restricted groups was inferior to adolescents in a prior sample given 9-hour nocturnal TIB. During both cycles of sleep restriction, blood glucose during the OGTT increased by a greater amount in the split sleep schedule compared with persons receiving 6.5-hour continuous sleep. In adolescents, modest multinight sleep restriction had divergent negative effects on cognitive performance and glucose levels depending on how the restricted sleep was apportioned. They are best advised to obtain the recommended amount of nocturnal sleep. https://clinicaltrials.gov/ct2/show/NCT03333512.

Abstract Objectives To evaluate the long-term effects of an oral appliance on clinical symptoms, respiratory sleep parameters, sleep quality, and sustained attention in patients with upper airway resistance syndrome (UARS) were compared with placebo. Methods This study was a randomized placebo-controlled clinical trial. Thirty UARS patients were randomized in two groups: placebo and mandibular advancement device (MAD) groups. UARS criteria were presence of sleepiness (Epworth Sleepiness Scale ≥ 10) and/or fatigue (Modified Fatigue Impact Scale ≥ 38) associated with an apnea/hypopnea index ≤ 5 and a respiratory disturbance index (RDI) > 5 events/hour of sleep, and/or flow limitation in more than 30% of total sleep time. All patients completed the Pittsburgh Sleep Quality Index (PSQI), the Functional Outcomes of Sleep Questionnaire, the Beck Anxiety and Depression Inventories, underwent full-night polysomnography, multiple sleep latency test, and Psychomotor Vigilance Test (PVT). Evaluations were performed before and after 1.5 years of treatment. Results RDI, number of respiratory effort–related arousal, percentage of total sleep time with flow limitation, and arousal index significantly decreased after 1.5 years of MAD treatment. PSQI total score improved, severity of depression symptoms decreased, and mean reaction time in the PVT, based on the first measurement taken at 8:00 am, significantly decreased (p = .03) at the end of the protocol. Conclusions The MAD was effective in decreasing respiratory events in UARS patients. For UARS, 1.5 years of oral appliance therapy also improved sleep quality and sustained attention, and decreased the severity of depression symptoms. Clinical Trial Efficacy of Oral Appliance for Upper Airway Resistance Syndrome: Randomized, Parallel, Placebo-Controlled Study, NCT02636621.

Rationale Sex-related differences in the clinical profiles of some insomnia medications have been previously reported. Objective To evaluate the clinical profile of suvorexant, a novel orexin receptor antagonist approved for treating insomnia at doses up to 20 mg, by sex subgroups. Methods Efficacy analyses by sex were based on pooled data from two similar phase 3, randomized, double-blind, placebo-controlled, 3-month trials in elderly (≥65 years) and non-elderly (18–64 years) insomnia patients. Two age-adjusted (non-elderly/elderly) dose regimes of 40/30 and 20/15 mg were evaluated, with fewer patients assigned to 20/15 mg. Efficacy was assessed by patient-reported outcomes ( N  = 1264 women, 707 men) and by polysomnography endpoints in ~75% of patients. Safety analyses by sex ( N  = 1744 women, 1065 men) included pooled data from the two 3-month trials plus 3-month data from a safety trial of 40/30 mg. Results The sex subgroup efficacy analyses mirrored the improvements seen for suvorexant 40/30 and 20/15 mg over placebo on patient-reported outcomes and polysomnography sleep maintenance and onset endpoints in the primary analyses; 95% CIs excluded zero in favor of suvorexant for most endpoints in both sexes, and similar efficacy was observed between sexes (95% CIs overlapped). Suvorexant was well-tolerated in women and men, although women in all treatment groups (including placebo) reported more adverse events than men. The most frequent adverse event was somnolence (women: 11.1% for 40/30 mg, 8.5% for 20/15 mg, 2.3% for placebo; men: 10.1% for 40/30 mg, 3.4% for 20/15 mg, 4.2% for placebo). Conclusion Suvorexant was generally effective and well-tolerated in both women and men with insomnia. ClinicalTrials.gov trial registration numbers: NCT01097616, NCT01097629, NCT01021813.

Background Obstructive sleep apnea syndrome (OSA) is currently recognized as an independent risk factor for hypertension, arrhythmia, coronary heart disease, stroke, and metabolic disorders (e.g. diabetes, dyslipidemia). In clinical practice, apnea-hypopnea index (AHI) is the marker used to classify disease severity and guide treatment. However, AHI alone does not sufficiently identify OSA patients at risk for cardiometabolic comorbidities. With this in mind, the aim of this retrospective study was to determine whether some polysomnographic parameters (e.g. apnea-hypopnea duration, sleep structure, nocturnal hypoxemia) are specifically associated with cardiometabolic comorbidities in OSA. Methods In this retrospective study, 1717 patients suffering from moderate/severe OSA were included between 2013 and 2017. Data on demographics, comorbidities, and polysomnographic characteristics were collected and analyzed to identify factors associated with cardiometabolic complications. Results The medical files of 1717 patients (68% male) were reviewed. The mean AHI was 43.1 +/− 27.7 with 57.3% of patients suffering from severe OSA, and 52% from at least one cardiovascular comorbidity (CVCo). Diabetes affected 22% of the patients and 27% exhibited dyslipidemia. Patients affected by CVCos were older, and more often women and non-smokers. These patients also had worse sleep quality, and a more marked intermittent/global nocturnal hypoxemia. With regard to diabetes, diabetics were older, more often non-smoker, non-drinker women, and were more obese. These patients also exhibited more severe OSA, especially in non-REM (NREM) sleep, worse sleep quality, and a more marked intermittent/global nocturnal hypoxemia. Dyslipidemia was more frequent in the absence of alcohol consumption, and was associated with OSA severity, decreased sleep quality, and longer AH in REM sleep. Conclusions This study identifies demographic and polysomnographic factors associated with cardiometabolic comorbidities. Patients (especially women) suffering from more severe OSA, longer sleep apneas and hypopneas, worse sleep quality, and marked intermittent/global nocturnal hypoxemia are more likely to develop cardiometabolic comorbidities. This should stimulate clinicians to obtain adequate treatment in this population.

To describe racial/ethnic differences in sleep duration, continuity, and perceived sleep quality in postmenopausal women and to identify statistical mediators of differences in sleep characteristics. Recruited from the observational Study of Women's Health Across the Nation (SWAN), 1,203 (548 white, 303 black, 147 Chinese, 132 Japanese, and 73 Hispanic; mean age 65 years, 97% postmenopausal) women participated in a week-long actigraphy and daily diary study in 2013-2015. Actigraphic measures of sleep duration and wake after sleep onset (WASO), and diary-rated sleep quality were averaged across the week. Candidate mediators included health-related variables; stress; and emotional well-being assessed up to 13 times across 18 years from baseline to sleep study. Whites slept longer than other groups; the significant mediators were concurrent financial hardship and increasing number of stressors for Hispanics or Japanese versus whites. Whites had less WASO than blacks and Hispanics; significant mediators were concurrent number of health problems, physical inactivity, waist circumference, vasomotor symptoms, number of life stressors, and financial hardship, and increasing number of health problems from baseline to sleep study. Whites reported better sleep quality than blacks, Chinese, and Japanese; significant mediators were concurrent physical inactivity, vasomotor symptoms, positive affect, and depressive symptoms. Sleep differences between blacks or Hispanics versus whites were mediated by health problems, number of stressors, and financial hardship, whereas sleep differences between Chinese or Japanese versus whites were mediated by emotional well-being. This is the first study using formal mediational approaches.

To assess the effect of adenotonsillectomy for relieving obstructive sleep apnea syndrome (OSAS) symptoms in children on cardiac autonomic modulation. In 354 children enrolled in the Childhood Adenotonsillectomy Trial, randomized to undergo either early adenotonsillectomy (eAT; N = 181) or a strategy of watchful waiting with supportive care (WWSC; N = 173), nocturnal heart rate control was analyzed during quiet, event-free sleep at baseline and at 7 months using overnight polysomnography (PSG). The relative frequency of patterns indicating monotonous changes in heart rate was quantified. Children who underwent eAT demonstrated a significantly greater reduction in heart rate patterns postsurgery than the WWSC group. On assessing those heart rate patterns regarding normalization of clinical PSG, heart patterns were reduced to a similar level in both groups. In children whose AHI normalized spontaneously, heart rate patterns were already significantly less frequent at baseline, suggesting that upper airway obstruction was milder in this group at the outset. Adenotonsillectomy reduces monotonous heart rate patterns throughout quiet event-free sleep, reflecting a reduction in cardiac autonomic modulation. Heart rate pattern analysis may help quantifying the effect of OSAS on autonomic nervous system activity in children. Clinical Trial Registration: The study was registered at Clinicaltrials.gov (#NCT00560859).

The contribution of ventilatory control to the pathogenesis of obstructive sleep apnea (OSA) in children and the effect of adenotonsillectomy are unknown. We aimed to examine the difference in ventilatory control between children with OSA and those without OSA. We also examined the effect of adenotonsillectomy on parameters of ventilatory control. Healthy children with OSA and matched controls were recruited. Polysomnography was performed before adenotonsillectomy in the OSA group and 6 months postoperatively. Controls underwent the same assessment at the two time points. Loop gain (LG), controller gain (CG), and plant gain (PG), which reflect the stability of ventilatory control, chemoreceptor sensitivity and the pulmonary control of blood gas in response to a change in ventilation, respectively, were estimated from polysomnographic tracings which included spontaneous sighs and tracings with tidal breathing. A linear mixed model was used to examine the changes of the ventilatory control parameters from baseline to 6 months. Ninety-nine children aged 7-13 were recruited to the study. Fifty-three with OSA and 46 controls. At baseline, compared with controls, children with OSA had higher PG and lower CG. LG did not differ between groups. Six months following adenotonsillectomy, there was a significant decrease in PG in the OSA group, while no change observed in the control group. The study demonstrates that the pulmonary control of blood gas homeostasis is disturbed in children with OSA and it normalizes following adenotonsillectomy.

Rapid eye movement (REM) sleep is characterized by the alternation of two markedly different microstates, phasic and tonic REM. These periods differ in awakening and arousal thresholds, sensory processing, and spontaneous cortical oscillations. Previous studies indicate that although in phasic REM, cortical activity is independent of the external environment, attentional functions and sensory processing are partially maintained during tonic periods. Large-scale synchronization of oscillatory activity, especially in the α- and β-frequency ranges, can accurately distinguish different states of vigilance and cognitive processes of enhanced alertness and attention. Therefore, we examined long-range inter- and intrahemispheric as well as short-range electroencephalographic synchronization during phasic and tonic REM periods quantified by the weighted phase lag index. Based on the nocturnal polysomnographic data of 19 healthy adult participants, we showed that long-range inter- and intrahemispheric α and β synchrony was enhanced in tonic REM states in contrast to phasic ones, and resembled α and β synchronization of resting wakefulness. On the other hand, short-range synchronization within the γ-frequency range was higher in phasic compared with tonic periods. Increased short-range synchrony might reflect local and inwardly driven sensorimotor activity during phasic REM periods, whereas enhanced long-range synchrony might index frontoparietal activity that reinstates environmental alertness after phasic REM periods.

To investigate the effects of caffeine on psychomotor vigilance and sleepiness during sleep restriction and following subsequent recovery sleep. Participants were N = 48 healthy good sleepers. All participants underwent five nights of sleep satiation (time-in-bed [TIB]: 10 hours), followed by five nights of sleep restriction (TIB: 5 hours), and three nights of recovery sleep (TIB: 8 hours) in a sleep laboratory. Caffeine (200 mg) or placebo was administered in the form of chewing gum at 08:00 am and 12:00 pm each day during the sleep restriction phase. Participants completed hourly 10-minute psychomotor vigilance tests and a modified Maintenance of Wakefulness Test approximately every 4 hours during the sleep restriction and recovery phases. Caffeine maintained objective alertness compared to placebo across the first 3 days of sleep restriction, but this effect was no longer evident by the fourth day. A similar pattern of results was found for Maintenance of Wakefulness Test sleep latencies, such that those in the caffeine group (compared to placebo) did not show maintenance of wakefulness relative to baseline after the second night of restriction. Compared to placebo, participants in the caffeine condition displayed slower return to baseline in alertness and wakefulness across the recovery sleep period. Finally, the caffeine group showed greater N3 sleep duration during recovery. Caffeine appears to have limited efficacy for maintaining alertness and wakefulness across 5 days of sleep restriction. Perhaps more importantly, there may be recovery costs associated with caffeine use following conditions of prolonged sleep loss.