A comparison of two screening tools for paediatric obstructive sleep apnea.

Untreated obstructive sleep apnea in children is associated with significant medical and psychological morbidities. Polysomnographic testing is the gold-standard method for diagnosis of obstructive sleep apnea. However, laboratory-based polysomnography is expensive and associated with a substantial healthcare burden. Thus, a simple valid tool to accurately identify those at high risk of obstructive sleep apnea is essential. We performed a retrospective cross-sectional study of children referred to the Youthdale Child and Adolescent Sleep Clinic. Data were collected from questionnaires and sleep studies reports of 395 children. A comparison between two screening tools for paediatric obstructive sleep apnea - a six-item (parent-response) and an eight-item IF-SLEEPY/IM-SLEEPY scales - was performed. The results showed that 42% of the children (n = 164) were diagnosed with obstructive sleep apnea. The six-item scale (score ≥3) exhibited a sensitivity of 17% and a specificity of 95% for diagnosing obstructive sleep apnea. The eight-item IF-SLEEPY scale displayed 82% sensitivity and 28% specificity. The IM-SLEEPY scale exhibited 79% sensitivity and 32% specificity. In children ≥7 years old, the IF-SLEEPY (parent-response) had a sensitivity of 82% and specificity of 28% compared with the child-response (66% and 37%, respectively). Logistic regression analysis revealed that age (odds ratio = 0.78), IF-SLEEPY/IM-SLEEPY score ≥3 (odds ratio = 1.78) and a score ≥2.72 on the six-item scale (odds ratio = 4.54) were predictors of obstructive sleep apnea. This study suggests that the eight-item scale is a better screening tool for paediatric obstructive sleep apnea, with a higher sensitivity and simple yes/no responses that are easy to complete and to score.

The STOP-BANG questionnaire shows an insufficient specificity for detecting obstructive sleep apnea in patients with atrial fibrillation.

Obstructive sleep apnea (OSA) is a sleep disorder associated with significant cardiovascular comorbidities, including cardiac arrhythmia. The STOP-BANG questionnaire is an eight-item self-report questionnaire designed to screen patients for OSA and was validated in preoperative surgical patients. The STOP items are snoring, daytime tiredness, observed apneas and high blood pressure. The BANG items are body mass index >35 kg/m2 , age >50 years, neck circumference >40 cm and male gender. We aimed to determine the screening properties of the STOP-BANG questionnaire in patients with arrhythmia. Non-selected consecutive patients were recruited from arrhythmia clinics. Patients with previously diagnosed and/or treated OSA were excluded. The STOP-BANG questionnaire was self-administered. Patients underwent two consecutive nights of home sleep recording. OSA was defined as an apnea-hypopnea index score of ≥5/hr of sleep. The screening properties of the STOP-BANG questionnaire were analysed compared with the objective diagnosis of OSA by ambulatory testing. Ninety-five patients were included in the final analysis. Eighty-five percent were found to have OSA. The STOP-BANG score of ≥3 was 89% sensitive and 36% specific for diagnosis of OSA. The STOP-BANG questionnaire had fair performance, as indicated by an area under the curve of 0.74 (p = .004). In conclusion, the STOP-BANG questionnaire is sensitive; however, it has a low specificity with a high false positive rate. Given that a large number of atrial fibrillation patients need testing for OSA, we recommend the use of a level II sleep study regardless of the results of the screening questionnaire. This approach accurately identifies OSA and may limit the cost of unnecessary level-I sleep studies.

Circadian Rhythms Disturbances in Alzheimer Disease: Current Concepts, Diagnosis, and Management.

The purpose of this review is to provide an overview of the research regarding circadian rhythms in Alzheimer disease (AD). Furthermore, this paper explores the role of melatonin in the pathogenesis of AD and the limitation of trials addressing circadian rhythms disturbances in the AD population. A literature search using Medline with PubMed and Embase was carried out identifying papers focusing on circadian rhythms in AD. Sleep disorders and especially circadian rhythm disturbances are very common in the elderly population but definitely more pronounced in patients with AD. The lack of trials evaluating the management of circadian rhythms disorders in the elderly population and especially in AD should be considered of the utmost importance. Although there is a better understanding about the pathophysiology of AD and its relationship with circadian disorders, further studies in human models need to be conducted.

An Overview of Psychogenic Non-Epileptic Seizures: Etiology, Diagnosis and Management.

The purpose of this review is to provide an update of the research regarding the etiology, diagnosis and management of psychogenic non-epileptic seizures (PNES). A literature search using Pubmed, Ovid MEDLINE and EMBASE database was performed from 2000 up to August 2017. We have evaluated the different factors leading to PNES as well as the diagnostic approach and management of this disorder which continue to be very difficult. The coexistence of epilepsy and PNES poses special challenges and requires the coordinated efforts of the family physicians, psychiatrists, psychologists and neurologists. Although this condition has an overall poor prognosis, a multidisciplinary approach in the diagnosis and management of this disorder would likely improve the outcomes. We have proposed a diagnostic and treatment algorithm for PNES and suggested a national registry of patients suffering from this condition. The registry would contain data regarding treatment and outcomes to aid in the understanding of this entity.

Modeling community integration in workers with delayed recovery from mild traumatic brain injury.

BACKGROUND: Delayed recovery in persons after mild traumatic brain injury (mTBI) is poorly understood. Community integration (CI) is endorsed by persons with neurological disorders as an important outcome. We aimed to describe CI and its associated factors in insured Ontario workers with delayed recovery following mTBI. METHODS: A cross-sectional study of insured workers in the chronic phase following mTBI was performed at a rehabilitation hospital in Ontario, Canada. Sociodemographic, occupational, injury-related, clinical, and claim-related data were collected from self-reports, medical assessments, and insurers' referral files. Community Integration Questionnaire (CIQ) scores were compared using analysis of variance or Spearman's correlation tests. Stepwise multivariable linear regression models were used to evaluate the associations with CI. RESULTS: Ninety-four workers with mTBI (45.2 ± 9.9 years old, 61.2% male) at 197 days post-injury (interquartile range, 139-416 days) were included. The CIQ total and subscale scores were similar to those reported in more severe TBI samples. The CIQ scores were moderately to strongly correlated with various sociodemographic, claim-related, and clinical variables. In the multivariable regression analysis, several covariates accounted for 36.4% of the CIQ variance in the final fully adjusted model. DISCUSSION: This study evaluated CI in workers with mTBI, and analyzed its associated variables. Analysis revealed insomnia, head or neck pain, being married or in a relationship, time since injury, and a diagnosis of possible/probable malingering were independently associated with limited CI. CONCLUSIONS: Workers with delayed recovery from mTBI experience difficulty with CI. Insomnia is a particularly relevant covariate, explaining the greater part of its variance. To enhance participation, care should focus on clinical and non-clinical covariates.

Postoperative sleep-disordered breathing in patients without preoperative sleep apnea.

BACKGROUND: Recently published data show that postoperative apnea-hypopnea index (AHI) is significantly increased in some patients without preoperative sleep apnea. These patients may be at risk of developing perioperative adverse events related to sleep-disordered breathing (SDB). The objective of this study was to investigate the incidence and predictors of postoperative moderate-to-severe SDB (AHI > 15 events/h) in patients without sleep apnea preoperatively. METHODS: In a prospective observational fashion, patients were invited to undergo sleep studies with a portable device (Embletta X100) preoperatively at home and postoperatively on the first and third night after surgery in the hospital or at home. The primary outcome was the incidence of postoperative moderate-to-severe SDB (AHI > 15 events/h) in non-sleep apnea patients (preoperative AHI ≤ 5 events/h). Logistic regression was used to evaluate the association of clinical factors and preoperative sleep parameters with the occurrence of postoperative moderate-to-severe SDB. RESULTS: A total of 120 non-sleep apnea patients completed the study, of which 31 (25.8% [95% confidence interval: 18.3%-34.6%]) patients were found to have AHI > 15 events/h on postoperative night 1 and/or postoperative night 3 (postoperative SDB group), and 89 (74%) patients had an AHI ≤ 15 events/h on both postoperative night 1 and 3 (postoperative non-SDB group). The patients in the postoperative SDB group were older (60 ± 13 vs 53 ± 12 years, P = 0.008) with more smokers (32.3% vs 15.7%, P = 0.048) and had a greater increase in the obstructive apnea index (adjusted P = 0.0003), central apnea index (adjusted P = 0.0012), and hypopnea index (adjusted P = 0.0004). Multivariate logistic regression analysis found that age and preoperative respiratory disturbance index (RDI) were significantly associated with the occurrence of postoperative moderate-to-severe SDB, P = 0.018 and P = 0.006, respectively. The sensitivity privilege cutoff of RDI at 4.9 events/h identified 70.2% to 96.4%patients developing postoperative moderate-to-severe SDB. CONCLUSIONS: At least 18.3% of non-sleep apnea patients developed moderate-to-severe SDB after surgery. Age and preoperative RDI were associated with the occurrence of postoperative moderate-to-severe SDB.

Home-use servo-ventilation therapy in chronic pain patients with central sleep apnea: initial and 3-month follow-up.

PURPOSE: Opioid treatment of non-malignant chronic pain can result in hypoxemia, hypercarbia, and central sleep apnea. The aim of this study was to determine the initial efficacy of auto servo-ventilation (ASV) and after 3 months of home use. METHODS: This prospective multicenter interventional study recruited chronic pain patients prescribed ≥100 morphine equivalents for at least 4 months. PARTICIPANTS: Following full-night polysomnography (PSG) to confirm the presence of sleep-disordered breathing, patients were randomized to three additional full-night-attended PSGs with continuous positive airway pressure (CPAP), ASV, and servo-ventilation with an initial mandatory pressure support of 6 cm H2O (ASV manual PSmin 6). Following the PSGs, patients were sent home with EncoreAnywhere and ASV with or without mandatory pressure support. RESULTS: Based on the initial PSG studies, CPAP improved but did not normalize the apnea-hypopnea index (AHI), central apnea index (CAI), or hypopnea index (HI), as all remained elevated. Clinically significant reductions were noted after just one night of ASV and ASV manual (PSmin 6). After 3 months of ASV home use, the AHI, CAI, and obstructive apnea index (OAI) were significantly reduced when compared to baseline diagnostic levels and even when compared to respiratory disturbance indices with CPAP treatment. CONCLUSIONS: Initial and home use of ASV for 3 months resulted in significantly lower AHI, CAI, and OAI. This reduction attests to the efficacy of ASV treatment in chronic pain patients on high doses of opioids.

Postoperative changes in sleep-disordered breathing and sleep architecture in patients with obstructive sleep apnea.

BACKGROUND: Anesthetics, analgesics, and surgery may profoundly affect sleep architecture and aggravate sleep-related breathing disturbances. The authors hypothesized that patients with preoperative polysomnographic evidence of obstructive sleep apnea (OSA) would experience greater changes in these parameters than patients without OSA. METHODS: After obtaining approvals from the Institutional Review Boards, consented patients underwent portable polysomnography preoperatively and on postoperative nights (N) 1, 3, 5, and 7 at home or in hospital. The primary and secondary outcome measurements were polysomnographic parameters of sleep-disordered breathing and sleep architecture. RESULTS: Of the 58 patients completed the study, 38 patients had OSA (apnea hypopnea index [AHI] >5) with median preoperative AHI of 18 events per hour and 20 non-OSA patients had median preoperative AHI of 2. AHI was increased after surgery in both OSA and non-OSA patients (P < 0.05), with peak increase on postoperative N3 (OSA vs. non-OSA, 29 [14, 57] vs. 8 [2, 18], median [25th, 75th percentile], P < 0.05). Hypopnea index accounted for 72% of the postoperative increase in AHI. The central apnea index was low (median = 0) but was significantly increased on postoperative N1 in only non-OSA patients. Sleep efficiency, rapid eye movement sleep, and slow-wave sleep were decreased on N1 in both groups, with gradual recovery. CONCLUSIONS: Postoperatively, sleep architecture was disturbed and AHI was increased in both OSA and non-OSA patients. Although the disturbances in sleep architecture were greatest on postoperative N1, breathing disturbances during sleep were greatest on postoperative N3.

Factors associated with postoperative exacerbation of sleep-disordered breathing.

INTRODUCTION: The knowledge on the mechanism of the postoperative exacerbation of sleep-disordered breathing may direct the perioperative management of patients with obstructive sleep apnea. The objective of this study is to investigate the factors associated with postoperative severity of sleep-disordered breathing. METHODS: After obtaining approvals from Institutional Review Boards, consenting patients underwent portable polysomnography preoperatively, and on postoperative nights 1 and 3 in hospital or at home. The primary outcomes were polysomnography parameters measuring the sleep-disordered breathing. They were treated as repeated measurement variables and analyzed for associated factors by mixed models. RESULTS: Three hundred seventy-six patients, 168 men and 208 women, completed polysomnography on preoperative and postoperative night 1. Age was 59 ± 12 yr (mean ± SD). Preoperative apnea-hypopnea index (AHI) was 12 (4, 26) (median [25th, 75th percentile]) events per hour. Thirty-five patients had minor surgeries, 292 intermediate surgeries, and 49 major surgeries, with 210 general anesthesia and 166 regional anesthesia. The 72-h opioid dose was 55 (14, 85) mg intravenous morphine-equivalent dose. Preoperative AHI, age, and 72-h opioid dose were associated with postoperative AHI. Preoperative central apnea index, male sex, and general anesthesia were associated with postoperative central apnea index. Slow wave sleep percentage was inversely associated with postoperative AHI and central apnea index. CONCLUSIONS: Patients with a higher preoperative AHI were predicted to have a higher postoperative AHI. Preoperative AHI, age, and 72-h opioid dose were positively associated with postoperative AHI. Preoperative central apnea, male sex, and general anesthesia were associated with postoperative central apnea index.

Sex differences and the interaction of age and sleep issues in neuropsychological testing performance across the lifespan in an ADD/ADHD sample from the years 1989 to 2009.

Chart review of population (9 to 80 years) neuropsychological test battery for ADHD diagnosis, questionnaires with multiple responders were evaluated in outpatient setting from 1989-2009. The focus was gender differences across age, diagnostic group (ADHD-Inattentive/ADHD plus), neuropsychological test performance, and reported sleep symptoms over the lifespan. Individuals were assigned to ADHD-I group or ADHD plus group (based upon secondary diagnosis of sleep, behavioral, emotional disturbance); ADHD not primary was excluded (brain insult, psychosis). Among these were 1,828 children (ages 9 to 14), adolescents (ages 15 to 17), and adults (ages 18 and above); 446 children (312 diagnosed ADHD-I), 218 adolescents (163 diagnosed ADHD-I), and 1,163 adults (877 ADHD-I). Sleep was problematic regardless of age, ADHD subtype, and gender. The type and number of sleep problems and fatigue were age dependent. ADHD subtype, gender, fatigue, age, and sleep (sleep onset, unrefreshing sleep, sleep maintenance) were significant variables affecting neuropsychological test performance (sequencing, cognitive flexibility, slow- and fast-paced input, divided attention, whole brain functioning). Findings suggest that ADHD involves numerous factors and symptoms beyond attention, such as sleep which interacts differently dependent upon age.

Improvement in sleep latency with extended-release once-nightly sodium oxybate for the treatment of adults with narcolepsy: Analysis from the phase 3 REST-ON clinical trial.

Background: In the REST-ON clinical trial (NCT02720744), mean sleep latency on the Maintenance of Wakefulness Test (MWT) was significantly improved with extended-release once-nightly sodium oxybate (ON-SXB) vs placebo (P < 0.001) in participants with narcolepsy. This post hoc analysis assessed response to treatment and improvement in excessive daytime sleepiness. Methods: Participants with narcolepsy aged ≥16 years were randomized 1:1 to receive ON-SXB (4.5 g, week 1; 6 g, weeks 2-3; 7.5 g, weeks 3-8; and 9 g, weeks 9-13) or placebo. Mean sleep latency on the MWT was measured across 5 trials of ≤30 min each. Post hoc assessments included percentage of participants whose sleep latency improved ≥5, ≥10, ≥15, and ≥20 min and with a mean sleep latency of 30 min. Results: Significantly more participants receiving ON-SXB vs placebo experienced increased mean sleep latency ≥5 min (all doses P < 0.001), ≥10 min (all doses P < 0.001), ≥15 min (6 and 7.5 g, P < 0.001; 9 g, P < 0.01), and ≥20 min (6 g, P < 0.01; 7.5 g, P < 0.001; 9 g, P < 0.05). More participants receiving ON-SXB had mean sleep latency of 30 min vs placebo (6 g, 5.7 % vs 0 %, respectively [P < 0.05]; 7.5 g, 10.5 % vs 1.3 % [P < 0.05]; 9 g, 13.2 % vs 5.1 % [P = 0.143]). Conclusions: Significantly more participants who received ON-SXB experienced increased mean sleep latency ≥5 to ≥20 min; at the 2 highest doses, >10 % remained awake for the entirety of the MWT. ON-SXB offers a once-at-bedtime treatment option for adults with narcolepsy.

Perioperative auto-titrated continuous positive airway pressure treatment in surgical patients with obstructive sleep apnea: a randomized controlled trial.

BACKGROUND: Obstructive sleep apnea (OSA) may worsen postoperatively. The objective of this randomized open-label trial is to determine whether perioperative auto-titrated continuous positive airway pressure (APAP) treatment decreases postoperative apnea hypopnea index (AHI) and improves oxygenation in patients with moderate and severe OSA. METHODS: The consented patients with AHI of more than 15 events/h on preoperative polysomnography were randomized into the APAP or control group (receiving routine care). The APAP patients received APAP for 2 or 3 preoperative, and 5 postoperative nights. All patients were monitored with oximetry for 7 to 8 nights (N) and underwent polysomnography on postoperative N3. The primary outcome was AHI on the postoperative N3. RESULTS: One hundred seventy-seven OSA patients undergoing orthopedic and other surgeries were enrolled (APAP: 87 and control: 90). There was no difference between the two groups in baseline data. One hundred six patients (APAP: 40 and control: 66) did polysomnography on postoperative N3, and 100 patients (APAP: 39 and control: 61) completed the study. The compliance rate of APAP was 45%. The APAP usage was 2.4-4.6 h/night. In the APAP group, AHI decreased from preoperative baseline: 30.1 (22.1, 42.5) events/h (median [25th, 75th percentile]) to 3.0 (1.0, 12.5) events/h on postoperative N3 (P < 0.001), whereas, in the control group, AHI increased from 30.4 (23.2, 41.9) events/h to 31.9 (13.5, 50.2) events/h, P = 0.302. No significant change occurred in the central apnea index. CONCLUSIONS: The trial showed the feasibility of perioperative APAP for OSA patients. Perioperative APAP treatment significantly reduced postoperative AHI and improved oxygen saturation in the patients with moderate and severe OSA.

Alcohol and sleep I: effects on normal sleep.

This review provides a qualitative assessment of all known scientific studies on the impact of alcohol ingestion on nocturnal sleep in healthy volunteers. At all dosages, alcohol causes a reduction in sleep onset latency, a more consolidated first half sleep and an increase in sleep disruption in the second half of sleep. The effects on rapid eye movement (REM) sleep in the first half of sleep appear to be dose related with low and moderate doses showing no clear trend on REM sleep in the first half of the night whereas at high doses, REM sleep reduction in the first part of sleep is significant. Total night REM sleep percentage is decreased in the majority of studies at moderate and high doses with no clear trend apparent at low doses. The onset of the first REM sleep period is significantly delayed at all doses and appears to be the most recognizable effect of alcohol on REM sleep followed by the reduction in total night REM sleep. The majority of studies, across dose, age and gender, confirm an increase in slow wave sleep (SWS) in the first half of the night relative to baseline values. The impact of alcohol on SWS in the first half of night appears to be more robust than the effect on REM sleep and does not appear to be an epiphenomenon REM sleep reduction. Total night SWS is increased at high alcohol doses across gender and age groups.

Sleep-laughing--hypnogely.

OBJECTIVE: To explain relatively common phenomenon of laughing during sleep and help to better define criteria for differentiating between physiological and pathological sleep-laughing. METHODS: Observational study of patients who underwent a sleep assessment in a referential tertiary health facility. RESULTS: A total of ten patients exhibited sleep laughing, nine of whom had episodes associated with rapid eye movement (REM) sleep. Also, in one of the patients sleep-laughing was one of the symptoms of REM sleep Behaviour Disorder, and in another patient sleep-laughing was associated with NREM sleep arousal parasomnia. CONCLUSION: The collected data and review of literature suggests that hypnogely in majority of the cases presents as a benign physiological phenomenon related to dreaming and REM sleep. Typically, these dreams are odd, bizarre or even unfunny for a person when awake. Nevertheless, they bring a sense of mirth and a genuine behavioural response. In a minority of cases, sleep-laughing appears to be a symptom of neurological disorders affecting the central nervous system. In these patients the behavioural substrate differs when compared to physiological laughing, and the sense of mirth is usually absent.

Oxygen desaturation index from nocturnal oximetry: a sensitive and specific tool to detect sleep-disordered breathing in surgical patients.

INTRODUCTION: It is impractical to perform polysomnography (PSG) in all surgical patients suspected of having sleep disordered breathing (SDB). We investigated the role of nocturnal oximetry in diagnosing SDB in surgical patients. METHOD: All patients 18 years and older who visited the preoperative clinics for scheduled inpatient surgery were approached for study participation. Patients expected to have abnormal electroencephalographic findings were excluded. All patients underwent an overnight PSG at home with a portable device and a pulse oximeter. The PSG recordings were scored by a certified sleep technologist. The oximetry recordings were processed electronically. RESULT: Four hundred seventy-five patients completed the study: 217 males and 258 females, aged 60 ± 11 years, and body mass index 31 ± 7 kg/m(2). The apnea-hypopnea index (AHI), the average number of episodes of apnea and hypopnea per hour of sleep, was 9.1 (2.8 to 21.4) [median (interquartile range)] and 64% patients had AHI >5. There was a significant correlation between oxygen desaturation index (ODI, hourly average number of desaturation episodes) and cumulative time percentage with SpO(2) <90% (CT90) from nocturnal oximetry, with the parameters measuring sleep breathing disorders from PSG. Compared to CT90, ODI had a stronger correlation and was a better predictor for AHI. The area under receiver operator characteristics curve for ODI to predict AHI >5, AHI >15, and AHI >30 was 0.908 (CI: 0.880 to 0.936), 0.931 (CI: 0.090 to 0.952), and 0.958 (CI: 0.937 to 0.979), respectively. The cutoff value based on the maximal accuracy for ODI to predict AHI >5, AHI >15, and AHI >30 was ODI >5, ODI >15, and ODI >30. The accuracy was 86% (CI: 83%-88%), 86% (CI: 83%-89%), and 94% (CI: 92%-96%), respectively. The ODI >10 demonstrated a sensitivity of 93% and a specificity of 75% to detect moderate and severe SDB. CONCLUSIONS: ODI from a high-resolution nocturnal oximeter is a sensitive and specific tool to detect undiagnosed SDB in surgical patients.

Health effects of identifying patients with undiagnosed obstructive sleep apnea in the preoperative clinic: a follow-up study.

BACKGROUND: Undiagnosed obstructive sleep apnea (OSA) is a highly prevalent breathing disorder. The purpose of this study was to determine the effects of preoperative screening and subsequent treatment for OSA on the health of patients. METHODS: We conducted a two-year follow-up study of patients previously enrolled in a large prospective study in which patients were given the STOP questionnaire for OSA screening (n = 2,467). All patients who underwent a polysomnography were considered eligible (n = 211) and were asked to complete a paper-based mailed questionnaire. The severity of OSA, comorbidities, and treatment modalities and their effects were evaluated from the returned questionnaire. Research ethics board approval was obtained and returning the questionnaire implied informed patient consent. RESULTS: The response rate was 67%. One hundred twenty-eight (82%) of the 156 patients who responded had OSA established by polysomnography. Among these 128 patients with OSA, 88 (69%) were prescribed continuous positive airway pressure (CPAP) therapy and 40 (31%) were prescribed other (non-CPAP) treatment. Among those 88 patients receiving CPAP, 40 (45%) were compliant and 48 (55%) were non-compliant. The CPAP compliant patients had a greater reduction in medication for comorbidities than the CPAP non-compliant or the other treatment group (38% vs 3% vs 0%, respectively; P < 0.001). A significant improvement in snoring, sleep quality, and daytime sleepiness was reported by CPAP compliant users compared with CPAP non-compliant or other treatment groups (P < 0.001). CONCLUSION: The preoperative patients who were identified to have OSA and were compliant with CPAP use may have health benefits in terms of improved snoring, sleep quality, and daytime sleepiness. Timely diagnosis and treatment compliance may reduce symptoms of OSA and severity of associated comorbidities along with a reduction in medications.

Once-nightly sodium oxybate (FT218) demonstrated improvement of symptoms in a phase 3 randomized clinical trial in patients with narcolepsy.

STUDY OBJECTIVES: To assess the efficacy and safety of FT218, a novel once-nightly formulation of sodium oxybate (ON-SXB), in patients with narcolepsy in the phase 3 REST-ON trial. METHODS: Narcolepsy patients aged ≥16 years were randomized 1:1 to uptitration of ON-SXB (4.5, 6, 7.5, and 9 g) or placebo. Three coprimary endpoints were change from baseline in mean sleep latency on the Maintenance of Wakefulness Test, Clinical Global Impression-Improvement rating, and weekly cataplexy attacks at 9, 7.5, and 6 g. Secondary endpoints included change from baseline on the Epworth Sleepiness Scale. Safety included adverse drug reactions and clinical laboratory assessments. RESULTS: In total, 222 patients were randomized; 212 received ≥1 dose of ON-SXB (n = 107) or placebo (n = 105). For the three coprimary endpoints and Epworth Sleepiness Scale, all three doses of ON-SXB demonstrated clinically meaningful, statistically significant improvement versus placebo (all p < 0.001). For ON-SXB 9 g versus placebo, increase in mean sleep latency was 10.8 versus 4.7 min (Least squares mean difference, LSMD [95% CI], 6.13 [3.52 to 8.75]), 72.0% versus 31.6% were rated much/very much improved on Clinical Global Impression-Improvement (OR [95% CI], 5.56 [2.76 to 11.23]), change in mean weekly number of cataplexy attacks was -11.5 versus -4.9 (LSMD [95% CI], -6.65 [-9.32 to -3.98]), and change in Epworth Sleepiness Scale was -6.5 and -2.7 (LSMD [95% CI], -6.52 [-5.47 to -2.26]). Common adverse reactions included nausea, vomiting, headache, dizziness, and enuresis. CONCLUSIONS: ON-SXB significantly improved narcolepsy symptoms; its safety profile was consistent with SXB. ON-SXB conferred efficacy with a clearly beneficial single nighttime dose. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02720744, https://clinicaltrials.gov/ct2/show/NCT02720744.

Spectral modulation attenuates molecular, endocrine, and neurobehavioral disruption induced by nocturnal light exposure.

The human eye serves distinctly dual roles in image forming (IF) and non-image-forming (NIF) responses when exposed to light. Whereas IF responses mediate vision, the NIF responses affect various molecular, neuroendocrine, and neurobehavioral variables. NIF responses can have acute and circadian phase-shifting effects on physiological variables. Both the acute and phase-shifting effects induced by photic stimuli demonstrate short-wavelength sensitivity peaking ≈450-480 nm. In the current study, we examined the molecular, neuroendocrine, and neurobehavioral effects of completely filtering (0% transmission) all short wavelengths <480 nm and all short wavelengths <460 nm or partially filtering (~30% transmission) <480 nm from polychromatic white light exposure between 2000 and 0800 in healthy individuals. Filtering short wavelengths <480 nm prevented nocturnal light-induced suppression of melatonin secretion, increased cortisol secretion, and disrupted peripheral clock gene expression. Furthermore, subjective alertness, mood, and errors on an objective vigilance task were significantly less impaired at 0800 by filtering wavelengths <480 nm compared with unfiltered nocturnal light exposure. These changes were not associated with significantly increased sleepiness or fatigue compared with unfiltered light exposure. The changes in molecular, endocrine, and neurobehavioral processes were not significantly improved by completely filtering <460 nm or partially filtering <480 nm compared with unfiltered nocturnal light exposure. Repeated light-dark cycle alterations as in rotating nightshifts can disrupt circadian rhythms and induce health disorders. The current data suggest that spectral modulation may provide an effective method of regulating the effects of light on physiological processes.

Perioperative practical experiences in using a level 2 portable polysomnography.

PURPOSE: The objective of the study is to test the hypothesis that a level 2 portable sleep device (Embletta X100) is a reliable alternative for standard PSG in surgical patients. METHODS: After hospital ethics approvals, preoperative patients over 18 years old were recruited. The patients for validation underwent standard PSG and Embletta X100 simultaneously in a sleep laboratory before surgery. The other patients received sleep studies with Embletta X100 perioperatively. The correlation analysis and paired Student t test between variables from Embletta and from standard PSG were used to evaluate the accuracy of Embletta. The quality of PSG recordings with Embletta was summarized. RESULT: Twenty-one patients completed sleep study on both systems; ten females and ten males, age was 54 ± 11 and BMI was 36 ± 9. There was a significant correlation between the majority of parameters from standard PSG and Embeltta X100 with manual scoring. The inter-rater agreement was substantial to perfect at different AHI cutoffs with a Kappa coefficient of 0.69 to 1. A significant correlation between standard PSG and Embletta X100 with automatic scoring was found only in AHI and a few other parameters. In 385 patients, 1,002 perioperative PSG recordings were carried out with Embletta. Of them, 889(88.7%) were technically good and 90(9%) technically acceptable. Only 23 (2.3%) PSG recordings failed. CONCLUSION: Embletta X100, installed by a well-trained sleep technician, is a good alternative when standard PSG was not available or impractical. Manual scoring by a certified PSG technologist is the key for reliable results.

Effect of sleeping in a head-up position on intraocular pressure in patients with glaucoma.

PURPOSE: To determine whether a 30-degree head-up sleeping position decreases nocturnal intraocular pressure (IOP) compared with lying flat in patients with glaucoma. DESIGN: Prospective, nonrandomized comparative case series. PARTICIPANTS: Seventeen eyes of 17 patients with glaucoma with controlled IOP and new disc hemorrhage. METHODS: Patients with a new disc hemorrhage despite well-controlled IOP were evaluated in a sleep laboratory on 2 separate nights, the first night lying flat and the second night in a 30-degree head-up position. Intraocular pressure and blood pressure (BP) were measured every 2 hours from 6 PM to 8 AM. For the 6 PM, 8 PM, 10 PM, and 8 AM measurements (awake period) the subjects were sitting for both nights. For the midnight, 2 AM, 4 AM, and 6 AM measurements (sleep period), the subjects were supine for the first night and 30 degrees head up for the second night. MAIN OUTCOME MEASURE: Difference in IOP during the sleep period (midnight to 6 AM) between lying flat and 30-degree head-up positions. RESULTS: Seventeen eyes of 17 patients were included. There were no significant differences (P=0.68) between the 2 study visits in IOP during the awake period (6 PM, 8 PM, 10 PM, and 8 AM) when patients were sitting upright. During the sleep period (midnight to 6 AM) the mean IOP was 3.2 mmHg lower in the 30-degree head-up position compared with the flat position (P=0.03; 95% confidence interval, 0.25-6.1 mmHg). Sixteen of 17 patients (94.1%) had lower IOP in the 30-degree head-up position. The reduction in IOP in the 30-degree head-up position was 20% or more in 35% of patients (6/17). There were no differences in BP or ocular perfusion pressure between the 2 positions. CONCLUSIONS: The 30-degree head-up sleeping position lowers IOP compared with the flat position. Although this effect varies between individual patients, mean IOP was 20% lower in one third of patients in this series. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.