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.

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.

Screening for obstructive sleep apnea amongst patients with retinal vein occlusion.

OBJECTIVE: To evaluate the prevalence and varying severity of obstructive sleep apnea (OSA) amongst those newly diagnosed with retinal vein occlusion (RVO), and screen patients with the use of 2 in-office-administered questionnaires validated against polysomnography. DESIGN: Prospective cross-sectional study. PARTICIPANTS: Consecutive adult patients (≥18 years of age) with a new diagnosis of RVO confirmed with intravenous fluorescein angiography were enrolled. METHODS: The study was conducted at a tertiary academic centre between March 22, 2017, and April 7, 2018. Patients completed the Berlin and STOP-BANG questionnaires screening for OSA at presentation. Diagnostic test properties of the 2 questionnaires compared with polysomnography at a certified sleep laboratory centre as the gold standard for detection of OSA were calculated. RESULTS: A total of 27 patients (37% females) with a mean (standard deviation) age of 69.6 (11.5) years completed the study. The diagnosis of OSA based on polysomnography was made in 96% (41% severe OSA) of patients with RVO. The Berlin questionnaire had a sensitivity of 43% (confidence interval [CI]: 22%-66%) and specificity of 67% (CI: 22%-96%). The STOP-BANG questionnaire had a sensitivity of 86% (CI: 64%-97%) and specificity of 50% (CI: 12%-88%). CONCLUSIONS: Given the high prevalence of severe OSA amongst those with a new diagnosis of RVO, all patients should be strongly considered for polysomnography. The use of in-office questionnaires may aid in triaging urgency of referrals.

Circadian rhythm in the assessment of postconcussion insomnia: a cross-sectional observational study.

BACKGROUND: Insomnia is a major predictor of adverse outcomes in mild traumatic brain injury (mTBI), including concussion; although insomnia symptoms may be due to various sleep disorders, those related to circadian rhythm sleep-wake disorders (CRSWDs) require specific assessment and treatment. The objective of the current study was to determine the prevalence of CRSWD in a sample of treatment-seeking people with chronic insomnia symptoms after an mTBI. METHODS: Participants aged 17-65 years who had experienced an mTBI and reported chronic insomnia were recruited from diverse community clinics in Ontario 3-24 months after their injury to participate in this cross-sectional observational study. Potential participants were screened by both telephone and intake interview. Exclusion criteria were alcohol or substance use disorders, preexisting brain disorder or previous neurosurgery, recent travel across more than 2 time zones or shift work. Assessments included a clinical interview, questionnaires, 2 weeks of actigraphy and a sleep diary, and a dim-light melatonin onset test. The main outcome measure was the proportion of patients with CRSWDs. RESULTS: Of the 50 participants (32 [64%] female; median age 39.5 yr), 13 (26% [standard deviation 12%]) had an CRSWD. The most common circadian diagnosis was delayed sleep-wake phase disorder (10 participants [20%]). INTERPRETATION: The prevalence of CRSWDs may be exceptionally high among people with chronic insomnia symptoms following mTBI. Proper detection and treatment of CRSWDs in this population is essential to facilitate recovery. The findings emphasize the relevance of a diagnostic circadian assessment in patients with mTBI presenting with chronic insomnia symptoms.

Measures of functional outcomes, work productivity, and quality of life from a randomized, phase 3 study of solriamfetol in participants with narcolepsy.

OBJECTIVE: Solriamfetol (formerly JZP-110), a dopamine/norepinephrine reuptake inhibitor, is approved in the US to improve wakefulness in adults with excessive daytime sleepiness associated with narcolepsy (75-150 mg/d) or obstructive sleep apnea (37.5-150 mg/d). In a randomized, double-blind, placebo-controlled trial in participants with narcolepsy, effects of solriamfetol on functional status, health-related quality of life (HRQoL), and work productivity were evaluated. METHODS: Participants with narcolepsy (N = 239) were randomized to solriamfetol 75, 150, or 300 mg, or placebo for 12 weeks. Outcome measures included the Functional Outcomes of Sleep Questionnaire short version (FOSQ-10), 36-Item Short Form Health Survey version 2 (SF-36v2), and Work Productivity and Activity Impairment questionnaire for Specific Health Problem (WPAI:SHP). A mixed-effects model with repeated measures was used for comparisons vs placebo. RESULTS: At week 12, solriamfetol increased FOSQ-10 total score, with greatest mean difference from placebo (95% CI) at 300 mg (1.45 [0.31, 2.59]). On SF-36v2, improvements vs placebo were observed in physical component summary scores (300 mg: 2.22 [0.04, 4.41]) and subscales of role physical, general health, and vitality. On WPAI:SHP, solriamfetol 150 mg reduced overall work impairment vs placebo (-15.5 [-29.52, -1.47]), and 150 and 300 mg reduced activity impairment vs placebo (-10.05 [-19.48, -0.62] and -13.49 [-23.19, -3.78], respectively). Most treatment-emergent adverse events (TEAEs) were mild or moderate in severity. Common TEAEs were headache, nausea, decreased appetite, nasopharyngitis, dry mouth, and anxiety. CONCLUSIONS: Solriamfetol improved measures of functional status, HRQoL, and work productivity, particularly at the 150- and 300-mg doses. Most TEAEs were mild to moderate. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02348593, EudraCT number 2014-005487-15.

Removing Short Wavelengths From Polychromatic White Light Attenuates Circadian Phase Resetting in Rats.

Visible light is the principal stimulus for resetting the mammalian central circadian pacemaker. Circadian phase resetting is most sensitive to short-wavelength (blue) visible light. We examined the effects of removing short-wavelengths < 500 nm from polychromatic white light using optical filters on circadian phase resetting in rats. Under high irradiance conditions, both long- (7 h) and short- (1 h) duration short-wavelength filtered (< 500 nm) light exposure attenuated phase-delay shifts in locomotor activity rhythms by (∼40-50%) as compared to unfiltered light exposure. However, there was no attenuation in phase resetting under low irradiance conditions. Additionally, the reduction in phase-delay shifts corresponded to regionally specific attenuation in molecular markers of pacemaker activation in response to light exposure, including c-FOS, Per1 and Per2. These results demonstrate that removing short-wavelengths from polychromatic white light can attenuate circadian phase resetting in an irradiance dependent manner. These results have important implications for designing and optimizing lighting interventions to enhance circadian adaptation.

Sleep and major depressive disorder: a review of non-pharmacological chronotherapeutic treatments for unipolar depression.

Depression is a significant public health issue, made worse by the absence of response to antidepressant medications by many patients. Given the high degree of overlap between sleep and circadian complaints and depression, chronotherapies are a promising avenue for novel, effective, and fast-acting treatments for depression. A critical literature review was conducted of bright light therapy (BLT) as a treatment for unipolar depression. Additionally, a separate critical literature review was also conducted of several promising, non-pharmacological, combination chronotherapeutic treatments, including BLT, sleep deprivation/wake therapy, and sleep phase advance. Results of BLT as a treatment for depression are encouraging, especially when used as an adjunct to antidepressant medications. It may also be desirable in special populations, such as geriatric and perinatal patients. Overall, results from combination chronotherapies are encouraging, though none has strong empirical support. Combining chronotherapies is an avenue of treatment which should be further explored.

Mandibular width as a novel anthropometric measure for assessing obstructive sleep apnea risk.

Craniofacial abnormalities are a known obstructive sleep apnea (OSA) risk factor, but still need to be better characterized. This study investigates the relationship between mandibular width and the risk of developing OSA.We retrospectively analyzed 3D reconstructions of head and neck computed tomography (CT) scans at our institution for mandibular width, neck circumference, neck fat volume (NFV), airway volume (AWV), and NFV:AWV ratio. Age, gender, and BMI were also documented. Patients were contacted to complete a STOP-BANG survey to assess OSA risk. Only patients with reconstructable scans and completed STOP-BANG questionnaires were included in the study. Survey results were analyzed to assess the correlation between mandible width and STOP-BANG. Mandible association was also compared to the associations of the other known risk factors.The final analysis included 427 patients with a mean age of 58.98 years (standard deviation = 16.77), 56% of whom were male. Mandibular width was found to positively correlate with STOP-BANG score (r = .416, P < .001). Statistically significant differences between mandible size for each risk group was seen (P < .001). After controlling for age and sex, mandible size was significantly different only for the low risk vs. high risk groups (odds ratio = 1.11; 95% confidence interval = 1.03-1.20; P = .007). Furthermore, when stratified according to mandible size, the small mandible group (<77.50 mm) predominantly consisted of low risk patients; the medium size mandible group (77.50-84.40 mm) was predominated by intermediate risk patients, and large mandible (>84.40 mm) was predominantly seen in high risk patients. Mandible width expressed a stronger association than NFV:AWV ratio, but neck circumference and NFV had stronger associations than did mandible width.In addition to previously documented OSA risk factors, mandibular width is positively correlated with OSA as an independent risk factor. Observation of a wide mandible (jaw) should raise awareness of OSA risk and increase screening methods when appropriate.

Longitudinal study of narcolepsy symptoms in first, second, and third-degree relatives of simplex and multiplex narcolepsy families.

OBJECTIVE: To assess the evolution of narcolepsy symptoms in first-, second, and third-degree relatives and to compare multiplex and simplex families. METHODS: A total of 4045 family members and 362 narcoleptic individuals were entered in the study; with 3255 family members interviewed twice, five to seven years apart. A control group (n = 178) composed of spouses or housemates was also interviewed twice. Family members were divided according to their blood relationship with the probands and further divided into multiplex (ie, more than one narcolepsy cases) and simplex (only one narcolepsy case) families. Telephone interviews were conducted with the help of the Sleep-EVAL system; narcolepsy probands were evaluated and diagnosed by a Sleep Specialist in a Sleep Clinic Center. RESULTS: A total of 1123 family members from 72 families were identified as members of multiplex families while the rest of the sample were a part of simplex families (n = 2132). Multiplex families had higher incidence and chronicity of hypersomnolence than the simplex family members and the control group. For cataplexy-like symptoms, only prevalence at the time of the first assessment distinguished multiplex (5.5%) and simplex (2.9%) families. Prevalence of sleep paralysis was higher among the first- and second-degree relatives coming from multiplex families, while incidence was the highest among second- and third-degree relatives. Hypnagogic hallucinations had similar prevalence between multiplex and simplex families but the incidence and chronicity were significantly higher among multiplex families. For each symptom, predictive factors were also determined in simplex and multiplex families. CONCLUSIONS: Our results show that individuals coming from multiplex families are at greater risks of a broad range of narcolepsy symptoms compared to simplex families.

Cardiac effects of CPAP treatment in patients with obstructive sleep apnea and atrial fibrillation.

PURPOSE: Obstructive sleep apnea (OSA) has been recognized as an independent risk factor for the development and progression of atrial fibrillation (AF). We aimed to investigate the changes in heart rate and atrial and ventricular ectopy after continuous positive airway pressure (CPAP) treatment in patients with OSA and AF. METHODS: Consecutive patients with AF underwent ambulatory sleep monitoring, and OSA was defined as an Apnea-Hypopnea-Index (AHI) ≥ 5/h. Treated patients completed in-laboratory CPAP titration study. A 24-h ECG Holter was performed at baseline and at 3 and 6 months after CPAP treatment. RESULTS: One hundred patients (70% males) with AF were included in the final analysis. OSA was diagnosed in 85% of patients. There were no significant changes in mean 24-h heart rate in patients with paroxysmal or permanent AF at 3 and 6 months of treatment compared to baseline. In patients with paroxysmal AF (n = 29), atrial and ventricular ectopy counts/24 h significantly decreased at 3 months compared to baseline (median (IQR) 351 (2049) to 57 (182), P = 0.002; 68 (105) to 16 (133), P = 0.01 respectively). At 6 months follow-up, the atrial ectopy count/24 h significantly decreased in patients with paroxysmal AF compared to baseline (median (IQR) 351 (2049) to 31 (113), P = 0.016, n = 14). In patients with permanent AF (n = 15), there was a significant reduction in ventricular ectopy count/24 h at 3 months compared to baseline (median (IQR) 100 (1116) to 33 (418), P = 0.02). CONCLUSIONS: There is a significant decrease in atrial and ventricular ectopy count/24 h in patients with AF and OSA at 3 and 6 months of CPAP treatment compared to baseline.

A Comparison of Two Nights of Ambulatory Sleep Testing in Arrhythmia Patients.

INTRODUCTION: Obstructive sleep apnea (OSA) is common and usually underdetected in patients with cardiac arrhythmia. Ambulatory sleep testing may provide an alternative method for detection of OSA under realistic conditions compared to in-laboratory polysomnography. We aimed to (1) determine the sleep architecture in arrhythmia patients; (2) detect differences in sleep parameters between patients with and without OSA; and (3) compare the results of two consecutive nights of unattended ambulatory sleep testing. METHODS: Consecutive patients with unknown OSA status were recruited from arrhythmia clinics. Patients underwent two consecutive nights of self-applied in-home sleep testing replete with electroencephalogram (EEG) recording. RESULTS: One hundred patients were recruited. The mean age was 64 ± 13 years (70% males). OSA (AHI ≥ 5/h) was detected in 85% of patients. In the total sample, the sleep efficiency was reduced, and sleep onset latency was longer compared to a reference population of the same age. In patients with OSA, the sleep efficiency and the percentage of slow wave sleep were reduced; however, the arousal and periodic limb movement indices were increased compared to patients without OSA. The two nights of the ambulatory sleep testing showed consistent results with an excellent test-retest reliability for the AHI (ICC = 0.813). REM latency was shorter during the second night of sleep recording (p = 0.02). There were no other significant differences in the sleep architecture, respiratory indices, and other sleep parameters between the first and the second night of the ambulatory sleep recording. CONCLUSIONS: There is no significant difference in the respiratory parameters obtained during two consecutive nights of ambulatory sleep testing. Ambulatory studies incorporating EEG may provide a reliable, convenient, and economically efficient method for sleep assessment and there appears to be no significant night-to-night variability.

L-Tryptophan As Treatment for Pediatric Non-Rapid Eye Movement Parasomnia.

OBJECTIVE: Parasomnias are common in childhood but there is no established treatment for parasomnias. The aim of this study was to (1) report on the outcome of using L-tryptophan to manage parasomnias in children and (2) examine sleep architecture and subjective psychological/sleep symptoms in children with parasomnia. METHOD: A retrospective analysis was conducted of charts of children (3-18 years old) who underwent polysomnographic testing and were diagnosed with primary parasomnia. Study patients were either prescribed L-tryptophan (daily dose range: 500-4500 mg, mean dose of 2400 mg) to manage their parasomnias or administered no treatment whereby parents/guardians declined treatment. Questionnaires assessing sleep and psychosocial symptoms were administered at the initial clinical consultation and a follow-up parasomnia outcome questionnaire was administered over the phone to parents/guardians. RESULTS: One hundred and sixty-five children (106 boys, 59 girls) received a sleep diagnosis of primary parasomnia. A significantly (p < 0.001) higher proportion (84%) of children taking L-tryptophan experienced improvements in their parasomnia symptoms compared with those (47%) who chose not to use L-tryptophan. Polysomnography revealed that children with parasomnias had an altered sleep architecture based on age-related normative values. Children with a diagnosis of parasomnia were also subjectively more fatigued and endorsed more depressive symptoms. CONCLUSIONS: This study finds that parasomnias in children are not benign and that treatment with L-tryptophan provides a favorable outcome. Children diagnosed with parasomnia had altered sleep architecture, were more fatigued, and endorsed depressive symptoms. This study supports the need to diagnose and treat parasomnias in children.

The prevalence of obstructive sleep apnea in patients with atrial fibrillation.

BACKGROUND: Obstructive sleep apnea (OSA) is a systemic disorder associated with significant cardiovascular complications. OSA may play a role in the initiation and worsening of atrial fibrillation (AF). This study aimed to determine the prevalence and clinical predictors of OSA in patients with AF. HYPOTHESIS: OSA is underdiagnosed in a large number of patients with AF and may not be predicted by conventional clinical indices. METHODS: Consecutive nonselected patients with AF were recruited from different arrhythmia clinics in Toronto, Ontario, Canada. Patients with previous diagnosis and/or treatment of OSA were excluded. Patients underwent 2 consecutive nights of ambulatory sleep testing with full electroencephalogram recording. OSA was defined as an Apnea-Hypopnea Index (AHI) score ≥ 5 per hour of sleep. RESULTS: 123 patients with AF were recruited, with 100 patients included in the final analysis. OSA was detected in 85% of these patients. 27% of patients with normal overall AHI had an increased AHI during rapid eye movement sleep. Only age and male sex were independent predictors of the presence of OSA in these patients. CONCLUSIONS: OSA is common and often undetected in patients with AF, especially in nonobese and/or female patients. Patients may have a normal overall AHI but an abnormal AHI during rapid eye movement sleep. The clinical relevance and therapeutic implications in this subgroup should be further investigated. The clinical features of OSA are not reliable predictors of OSA in patients with AF. A low threshold for detection of OSA, with sleep studies, in these patients may be merited.

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.

Risk of obstructive sleep apnea in open-angle glaucoma versus controls using the STOP-Bang questionnaire.

OBJECTIVE: To compare the percentage of patients at risk for obstructive sleep apnea (OSA) in open-angle glaucoma (OAG) versus controls using the STOP-Bang questionnaire. METHODS: This study used a cross-sectional survey. Patients with OAG and controls completed the STOP-Bang questionnaire-a validated tool to identify patients at high risk for OSA. Patients were considered at risk if they scored 3 or more points or at high risk for moderate/severe OSA if they scored 5 or more out of the maximum 8 points. Demographic information, medical history, and previous diagnosis of OSA were recorded. Details regarding the patients' glaucoma were obtained from their medical records. RESULTS: A total of 437 patients with OAG and 441 controls were included. The mean STOP-Bang score was 3.01 ± 1.3 for the glaucoma group and 3.03 ± 1.4 for the control group (p = 0.92). There was no significant difference between the percentage of subjects considered at risk for OSA (62.7% OAG vs 59.4% controls, p = 0.37) or at high risk for moderate/severe OSA (12.6% OAG vs 16.5% controls, p = 0.1). Significantly more patients in the control group had a previous diagnosis of OSA (p = 0.01). More patients with OAG reported feeling tired compared with controls (p = 0.003). A risk/high risk for OSA was not associated with glaucoma severity, progression, intraocular pressure control, or glaucoma type. CONCLUSIONS: Our results indicate that a risk or high risk for moderate/severe OSA as measured by the STOP-Bang questionnaire is not correlated with the presence or absence of glaucoma (regardless of the type), glaucoma severity, glaucoma progression, or IOP control.

Cognitive Behavioural Therapy for Insomnia (CBT-I) to treat depression: A systematic review.

INTRODUCTION: Major depressive disorder is one of the most commonly diagnosed psychiatric illnesses, and it has a profound negative impact on an individual's ability to function. Up to 90% of individuals suffering from depression also report sleep and circadian disruptions. If these disruptions are not effectively resolved over the course of treatment, the likelihood of relapse into depression is greatly increased. Cognitive Behavioural Therapy for Insomnia (CBT-I) has shown promise in treating these sleep and circadian disturbances associated with depression, and may be effective as a stand-alone treatment for depression. This may be particularly relevant in cases where antidepressant medications are not ideal (e.g. due to contraindications, cost, or treatment resistance). METHODS: A systematic literature review was conducted of trials investigating the use of CBT-I to treat depression in adults. Therapy included in-person CBT-I, as well as telehealth and group CBT-I. RESULTS AND CONCLUSIONS: CBT-I presents a promising treatment for depression comorbid with insomnia. In-person therapy has the most supporting evidence for its efficacy, though treatment effects may not be additive with those of antidepressant medications. Insomnia improvement due to CBT-I may mediate the improvement in depressive symptoms. There is less evidence for the use of telehealth, though a stepped-care approach is indicated based on baseline depressive severity. More research on group therapy and telehealth modalities of delivering CBT-I are required before making recommendations.

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.

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.

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.