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STUDY OBJECTIVES: Solriamfetol, a dopamine/norepinephrine reuptake inhibitor, is approved in the United States and European Union for excessive daytime sleepiness in adults with narcolepsy (75–150 mg/day) or obstructive sleep apnea (OSA; 37.5–150 mg/day). In 12-week studies, solriamfetol was associated with improvements in quality of life in participants with narcolepsy or OSA. These analyses evaluated the long-term effects of solriamfetol on quality of life. METHODS: Participants with narcolepsy or OSA who completed previous solriamfetol studies were eligible. A 2-week titration was followed by a maintenance phase ≤ 50 weeks (stable doses: 75, 150, or 300 mg/day). Quality of life assessments included Functional Outcomes of Sleep Questionnaire short version, Work Productivity and Activity Impairment Questionnaire: Specific Health Problem, and 36-Item Short Form Health Survey version 2. Mean (standard deviation) changes from baseline to end of study were evaluated. Data were summarized descriptively. Adverse events were assessed. RESULTS: Safety population comprised 643 participants (417 OSA, 226 narcolepsy). Solriamfetol improved Functional Outcomes of Sleep Questionnaire short version Total scores (mean change [standard deviation], 3.7 [3.0]) and 36-Item Short Form Health Survey version 2 Physical and Mental Component Summary scores (3.1 [6.9] and 4.3 [8.4], respectively); improvements were sustained throughout treatment. On Work Productivity and Activity Impairment Questionnaire: Specific Health Problem, solriamfetol reduced (improved) % presenteeism, % overall work impairment, and % activity impairment by a minimum of 25%. Common adverse events (≥ 5%): headache, nausea, nasopharyngitis, insomnia, dry mouth, anxiety, decreased appetite, and upper respiratory tract infection. CONCLUSIONS: Long-term solriamfetol treatment was associated with clinically meaningful, sustained improvements in functional status, work productivity, and quality of life for up to 52 weeks. Adverse events were similar between narcolepsy and OSA. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: A Long-Term Safety Study of JZP-110 in the Treatment of Excessive Sleepiness in Subjects with Narcolepsy or OSA; Identifier: NCT02348632; URL: https://clinicaltrials.gov/ct2/show/NCT02348632 CITATION: Weaver TE, Pepin J-L, Schwab R, et al. Long-term effects of solriamfetol on quality of life and work productivity in participants with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea. J Clin Sleep Med. 2021;17(10):1995–2007.

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.

Purpose Previous research has suggested the essential unidimensionality of the 12-item traditional Chinese version of the Nonrestorative Sleep Scale (NRSS). This study aimed to develop a short form of the traditional Chinese version of the NRSS without compromising its reliability and validity. Methods Data were collected from 2 cross-sectional studies with identical target groups of adults residing in Hong Kong. An iterative Wald test was used to assess differential item functioning by gender. Based on the generalized partial credit model, we first obtained a shortened version such that further shortening would result in substantial sacrifice of test information and standard error of measurement. Another shortened version was obtained by the optimal test assembly (OTA). The two shortened versions were compared for test information, Cronbach’s alpha, and convergent validity. Results Data from a total of 404 Chinese adults (60.0% female) who had completed the Chinese NRSS were gathered. All items were invariant by gender. A 6-item version was obtained beyond which the test performance substantially deteriorated, and a 9-item version was obtained by OTA. The 9-item version performed better than the 6-item version in test information and convergent validity. It had discrimination and difficulty indices ranging from 0.44 to 2.23 and − 7.58 to 2.13, respectively, and retained 92% of the test information of the original 12-item version. Conclusion The 9-item Chinese NRSS is a reliable and valid tool to measure nonrestorative sleep for epidemiological studies.

Background Sleep disturbance and its daytime sequelae, which comprise complex, transdiagnostic sleep problems, are pervasive problems in adolescents and young adults (AYAs) and are associated with negative outcomes. Effective interventions must be both evidence based and individually tailored. Some AYAs prefer self-management and digital approaches. Leveraging these preferences is helpful, given the dearth of AYA treatment providers trained in behavioral sleep medicine. We involved AYAs in the co-design of a behavioral, self-management, transdiagnostic sleep app called DOZE (Delivering Online Zzz’s with Empirical Support). Objective This study tests the feasibility and acceptability of DOZE in a community AYA sample aged 15-24 years. The secondary objective is to evaluate sleep and related outcomes in this nonclinical sample. Methods Participants used DOZE for 4 weeks (2 periods of 2 weeks). They completed sleep diaries, received feedback on their sleep, set goals in identified target areas, and accessed tips to help them achieve their goals. Measures of acceptability and credibility were completed at baseline and end point. Google Analytics was used to understand the patterns of app use to assess feasibility. Participants completed questionnaires assessing fatigue, sleepiness, chronotype, depression, anxiety, and quality of life at baseline and end point. Results In total, 83 participants created a DOZE account, and 51 completed the study. During the study, 2659 app sessions took place with an average duration of 3:02 minutes. AYAs tracked most days in period 1 (mean 10.52, SD 4.87) and period 2 (mean 9.81, SD 6.65), with a modal time of 9 AM (within 2 hours of waking). DOZE was appraised as highly acceptable (mode≥4) on the items “easy to use,” “easy to understand,” “time commitment,” and “overall satisfaction” and was rated as credible (mode≥4) at baseline and end point across all items (logic, confident it would work, confident recommending it to a friend, willingness to undergo, and perceived success in treating others). The most common goals set were decreasing schedule variability (34/83, 41% of participants), naps (17/83, 20%), and morning lingering in bed (16/83, 19%). AYAs accessed tips on difficulty winding down (24/83, 29% of participants), being a night owl (17/83, 20%), difficulty getting up (13/83, 16%), and fatigue (13/83, 16%). There were significant improvements in morning lingering in bed (P=.03); total wake time (P=.02); sleep efficiency (P=.002); total sleep time (P=.03); and self-reported insomnia severity (P=.001), anxiety (P=.002), depression (P=.004), and energy (P=.01). Conclusions Our results support the feasibility, acceptability, credibility, and preliminary efficacy of DOZE. AYAs are able to set and achieve goals based on tailored feedback on their sleep habits, which is consistent with research suggesting that AYAs prefer autonomy in their health care choices and produce good results when given tools that support their autonomy. Trial Registration ClinicalTrials.gov NCT03960294; https://clinicaltrials.gov/ct2/show/NCT03960294

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.

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.

BACKGROUND: Jet-lag may affect air-travelers crossing at least 2 time-zones and has several healthcare implications. It occurs when the human biological rhythms are out of synch with respect to the day-night cycle at the country destination. Its effect in psoriasis is missing. We aimed to evaluate the effect of Jet-lag in psoriatic patients’ management. METHODS: This is a prospective observational study that enrolled psoriatic patients that underwent a flight: patients who experienced jet-lag were compared to patients who did not experience jet-lag. Before the flight, a dermatologist recorded clinical and demographical data with particular attention to Psoriasis Area Severity Index (PASI) and Disease Activity in PSoriatic Arthritis (DAPSA). Patients performed Self-Administered Psoriasis Area Severity Index (SAPASI), the Dermatology Life Quality Index (DLQI) and the pruritus Visual Analog Scale (VAS) scores. After the flight, patients completed the SAPASI, DLQI and pruritus-VAS scores. RESULTS: The sample recruited comprised of 70 psoriatic patients aged 42.4 ± 9.7 years (median 42.5 years). Thirty (42.9%) were males, mean BMI was 25.5 ± 2.2 kg/m(2). Average disease duration was 15.2 ±7.1 years, and 20 (28.6%) subjects had developed PsA. Average hours of flight were 5.4 ±3.5 (median 3.5 hours), with 34 (48.6%) subjects reporting jet-lag. At the multivariate regression analysis, the change in the SAPASI score resulted correlated with jet-lag (regression coefficient 1.63, p = 0.0092), as well the change in the DLQI score (regression coefficient = 1.73, p = 0.0009), but no change on the pruritus VAS scale was found. CONCLUSIONS: The present study suggests that jet-lag may influence disease severity and DLQI scores, but not itch in psoriatic patients.

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.

Objective Solriamfetol (JZP‐110) is a selective dopamine and norepinephrine reuptake inhibitor with wake‐promoting effects. This phase 3 study ({"type":"clinical-trial","attrs":{"text":"NCT02348593","term_id":"NCT02348593"}}NCT02348593) evaluated the safety and efficacy of solriamfetol in narcolepsy.

Objective To establish in an exploratory neuroimaging study whether γ-hydroxybutyrate (sodium oxybate [SO]), a sedative, anti-narcoleptic drug with abuse potential, transiently inhibits striatal dopamine release in the human. Methods Ten healthy participants (30 years; 6M, 4F) and one participant with narcolepsy received a baseline positron emission tomography scan of [C-11]raclopride, a D2/3 dopamine receptor radioligand sensitive to dopamine occupancy, followed approximately one week later by an oral sedative 3g dose of SO and two [C-11]raclopride scans (1 h, 7 h post SO). Plasma SO levels and drowsiness duration were assessed. Results No significant changes were detected in [C-11]raclopride binding in striatum overall 1 or 7 h after SO, but a small non-significant increase in [C-11]raclopride binding, implying decreased dopamine occupancy, was noted in limbic striatal subdivision at one hour (+6.5%; p uncorrected = 0.045; +13.2%, narcolepsy participant), returning to baseline at 7 h. A positive correlation was observed between drowsiness duration and percent change in [C-11]raclopride binding in limbic striatum (r = 0.73; p = 0.017). Conclusions We did not find evidence in this sample of human subjects of a robust striatal dopamine change, as was reported in non-human primates. Our preliminary data, requiring extension, suggest that a 3g sedative SO dose might cause slight transient inhibition of dopamine release in limbic striatum.

This study aimed to assess the measurement properties of a simplified Chinese version of the Nonrestorative Sleep Scale (NRSS) among adolescents. We obtained a simplified Chinese NRSS by the standard forward-backward translation procedures and administered it to 486 students who were attending Grade 7-11 in Nanjing, China. Furthermore, Pittsburgh Sleep Quality Index, Athens Insomnia Scale, Centre for Epidemiological Studies Depression Scale, and Toronto Hospital Alertness Test were also self-completed for measuring sleep quality, insomnia, depression and alertness respectively. The sample was randomly split into two halves, with the first half used to explore the scale structure by exploratory factor analysis (EFA), and the second half used to confirm the identified structure by confirmatory factor analysis (CFA). A total of 481 adolescents (49% male) with a mean age of 16 years (range: 13-18) completed this study. In the other half of 250 adolescents, the root mean square error of approximation (RMSEA), standardised root mean square residual, and comparative fit index (CFI) in CFA, which tested the four-factor structure obtained from EFA, were 0.062, 0.051 and 0.975, respectively. Convergent validity was demonstrated from a significant correlation of the simplified Chinese NRSS with sleep quality (r = -0.62), insomnia (r = -0.71), depression (r = -0.60) and alertness (r = 0.54). The internal consistency and test-retest reliability for the global scale were 0.83 and 0.86 respectively. Measurement invariance was established between males and females with the changes of both CFI and RMSEA

A questionnaire is an instrument that consists of sets of open- and closed-ended questions with the aim to gather information from respondents. It can be used in clinical and research setting. In sleep medicine, as in other medical branches, questionnaires are used for different reasons. They give the sleep specialist an accurate and quick way to screen for different sleep problems which even the patient may not pay attention to. Questionnaires can also be used as a reference point to measure a patient’s progress. Furthermore, they can facilitate parents and caregiver’s verbalization of their child’s sleep difficulties. It is important to note that the number of pediatric sleep questionnaires is fewer compared to that available for adults. The limited number of pediatric sleep questionnaires might be due to difficulty in designing scales that can be used for a range of ages. This chapter reviews 19 sleep questionnaires in details that can be used to address a wide range of sleep difficulties. Those questionnaires are used widely in sleep clinics.

Introduction Le solriamfetol est un inhibiteur de la recapture de dopamine et de noradrenaline indique pour traiter les SDE associees a la narcolepsie (FDA). Il a recu l’avis positif du CHMP. Objectifs Evaluer l’efficacite et la securite d’emploi du solriamfetol chez des patients atteints de narcolepsie ( NCT 02348593 ) presentant ou non des cataplexies. Patients et methodes Des patients narcoleptiques avec cataplexie (NWC ; n = 117) ou sans (NWOC ; n = 114) ont recu 12 semaines de traitement par solriamfetol (75 mg, 150 mg, 300 mg) ou placebo. L’efficacite etait mesuree dans les deux groupes sur le test du maintien de l’eveil (TME), l’echelle de somnolence d’Epworth (ESS), et l’echelle d’impression globale de changement du patient (PGI-C). La securite d’emploi dont les evenements indesirables (EI) ont ete evalues. Resultats A baseline, les patients avec et sans cataplexie presentaient des performances similaires au TME et a l’ESS. Apres 12 semaines de traitement, les differences au TME vs placebo (IC a 95 %) etaient : NWC : 75 mg : 1,6 (−3,6, 6,9), 150 mg : 6,1 (0,7, 11,4) et 300 mg : 8,9 (3,5, 14,2) et NWOC : 75 mg : 3,4 (−1,9, 8,7), 150 mg : 9,1 (3,8, 14,3), 300 mg : 11,2 (5,8, 16,6). Les EI frequents etaient similaires entre les groupes. Discussion Apres 12 semaines de traitement, les differences a l’ESS vs placebo (IC a 95 %) etaient : NWC : 75 mg : −1,3 (−3,9, 1,3), 150 mg : −3,7 (−6,4, −1,1) et 300 mg : − 4,5 (−7,1, −1,9) et NWOC : 75 mg : −3,0 (−5,6, −0,4), 150 mg : −3,7 (−6,3, −1,2) et 300 mg : −4,9 (−7,6, −2,2). Amelioration similaire sur le PGI-C pour les deux groupes. Conclusion Le solriamfetol a demontre son efficacite pour traiter les SDE de patients narcoleptiques avec ou sans cataplexie. Le profil de tolerabilite correspond aux donnees des etudes precedentes.

Background Solriamfetol, a dopamine/norepinephrine reuptake inhibitor, improved wakefulness and reduced excessive daytime sleepiness (EDS) in studies of participants with narcolepsy with and without cataplexy. Objective Prespecified subgroup analyses of data from a 12-week randomized, double-blind, placebo-controlled, phase III trial of solriamfetol for EDS in narcolepsy evaluated the efficacy and safety of solriamfetol by cataplexy status. Methods Participants with narcolepsy received solriamfetol (75, 150, or 300 mg/day) or placebo and were stratified by cataplexy status. Coprimary endpoints were change from baseline on Maintenance of Wakefulness Test (MWT) and Epworth Sleepiness Scale (ESS); Patient Global Impression of Change (PGI-C) was the key secondary endpoint. Change in frequency of cataplexy attacks was evaluated in participants reporting cataplexy at baseline. Safety was evaluated. No adjustments were made for multiple comparisons; thereforepvalues are nominal. Results There were 117 participants in the cataplexy subgroup and 114 in the non-cataplexy subgroup. At week 12, least-squares (LS) mean (95% confidence interval [CI]) differences from placebo on change from baseline in MWT for solriamfetol 75, 150, and 300 mg in the cataplexy subgroup were 1.6 (- 3.6 to 6.9), 6.1 (0.7-11.4), and 8.9 (3.5-14.2) minutes, respectively (p < 0.05; 150 and 300 mg), and in the non-cataplexy subgroup were 3.4 (- 1.9 to 8.7), 9.1 (3.8-14.3), and 11.2 (5.8-16.6) minutes, respectively (p < 0.001; 150 and 300 mg). At week 12, LS mean (95% CI) differences from placebo on ESS change from baseline for solriamfetol 75, 150, and 300 mg in the cataplexy subgroup were - 1.3 (- 3.9 to 1.3), - 3.7 (- 6.4 to - 1.1), and - 4.5 (- 7.1 to - 1.9), respectively (p < 0.01; 150 and 300 mg), and in the non-cataplexy subgroup were - 3.0 (- 5.6 to - 0.4), - 3.7 (- 6.3 to - 1.2), and - 4.9 (- 7.6 to - 2.2), respectively (p < 0.05; all doses). For PGI-C at week 12, the mean percentage difference from placebo (95% CI) for solriamfetol 75, 150, and 300 mg in the cataplexy subgroup was 10% (- 15 to 35), 33% (9-57), and 39% (16-61), respectively (p < 0.05; 150 and 300 mg), and in the non-cataplexy subgroup was 48% (25-70), 44% (21-67), and 52% (30-73), respectively (p < 0.001; all doses), with somewhat differential treatment effects for 75 mg by cataplexy status. No changes in the number of cataplexy attacks were observed for solriamfetol compared with placebo (mean +/- standard deviation changes: - 3.6 +/- 13.3 [combined solriamfetol] and - 3.5 +/- 9.8 [placebo]). Common adverse events (headache, nausea, decreased appetite, and nasopharyngitis) were similar between cataplexy subgroups. Conclusions These data strongly indicate that solriamfetol was effective in treating EDS in participants with narcolepsy with or without cataplexy, as indicated by robust effects on MWT, ESS, and PGI-C. The safety profile was similar regardless of cataplexy status.

Background Alertness is an important part of attention which is different from the opposite of sleepiness. This study aimed to translate and assess the measurement properties of the Toronto Hospital Alertness Test (THAT) in Hong Kong Chinese population. Methods The standard forward-backward translation procedure and cognitive debriefing were conducted to obtain the Chinese THAT. One hundred Chinese adults completed the Chinese THAT, the Center for Epidemiological Studies Depression Scale (CES-D), the Pittsburgh Sleep Quality Index (PSQI), and the Athens Insomnia Scale (AIS) by telephone interviews. Results The factorial validity was assessed by confirmatory factor analysis, and the internal reliability was examined by coefficient omega. The two negatively worded items of the THAT had low factor loadings and were removed. One more item was removed based on the modification indices of the eight-item model. The remaining seven-item THAT showed satisfactory unidimensionality with root mean square error of approximation (RMSEA) = 0.06, standardized root mean square residual (SRMR) = 0.08, and comparative fit index (CFI) = 1.00. The coefficient omega of the seven-item Chinese THAT was 0.80 (95% CI: 0.74–0.86). Convergent validity was demonstrated with THAT moderately associated with CES-D (r = − 0.45, P r = − 0.40, P r = − 0.45, P Conclusions The Chinese version of THAT demonstrated acceptable reliability and validity in a Chinese population.

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.

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.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.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.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.

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 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.

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.

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.

Introduction Disturbed nocturnal sleep (DNS) is a common symptom in patients with narcolepsy, characterized by fragmented sleep, including frequent brief nightly awakenings. Sodium oxybate (SO) is an effective treatment for narcolepsy; however, currently available formulations must be taken twice nightly. FT218 is an investigational once-nightly controlled-release formulation of SO. Here, we evaluated the efficacy of FT218 on polysomnographic (PSG) measures of DNS and number of arousals (NAs) in patients with narcolepsy types 1 and 2. Methods This was a randomized, double-blind, placebo-controlled, multicenter study. Patients with narcolepsy aged ≥16 years were randomized 1:1 to receive FT218 or matching placebo: 4.5 g/night for 1 week, 6.0 g/night for 2 weeks, 7.5 g/night for 5 weeks, and 9.0 g/night for 5 weeks. Secondary endpoints included PSG measurements of DNS (defined as shifts to wake/N1 from N1, N2, N3, and REM) and NAs (defined per AASM Scoring Manual guidelines [v2.6]). Results Patients receiving FT218 had significant improvements vs placebo in DNS; the LS mean difference between FT218 and placebo was −22.63 for 9.0 g (week 13), −17.70 for 7.5 g (week 8), and −11.00 for 6.0 g (week 3) (all P Conclusion FT218 at all evaluated doses showed significant reduction in DNS and number of NAs vs placebo for all doses of FT218 evaluated. FT218 was generally well tolerated; the most common adverse events were consistent with known SO side effects. FT218 could offer a new once-nightly treatment option for DNS in patients with narcolepsy as demonstrated by PSG measures. Support (if any) Avadel Pharmaceuticals.

Objective and background Sleep stage disruption in persons with mild traumatic brain injury (mTBI) has received little research attention. We examined deviations in sleep stage distribution in persons with mTBI relative to population age- and sex-specific normative data and the relationships between such deviations and brain injury-related, medical/psychiatric, and extrinsic factors. Patients and methods We conducted a cross-sectional polysomnographic investigation in 40 participants diagnosed with mTBI (mean age 47.54 ± 11.30 years; 56% males). Measurements At the time of investigation, participants underwent comprehensive clinical and neuroimaging examinations and one full-night polysomnographic study. We used the 2012 American Academy of Sleep Medicine recommendations for recording, scoring, and summarizing sleep stages. We compared participants' sleep stage data with normative data stratified by age and sex to yield z -scores for deviations from available population norms and then employed stepwise multiple regression analyses to determine the factors associated with the identified significant deviations. Results In patients with mTBI, the mean duration of nocturnal wakefulness was higher and consolidated sleep stage N2 and REM were lower than normal ( p p = 0.018, and p = 0.010, respectively). In multivariate regression analysis, several covariates accounted for the variance in the relative changes in sleep stage duration. No sex differences were observed in the mean proportion of non-REM or REM sleep. Conclusions We observed longer relative nocturnal wakefulness and shorter relative N2 and REM sleep in patients with mTBI, and these outcomes were associated with potentially modifiable variables. Addressing disruptions in sleep architecture in patients with mTBI could improve their health status.

To determine the difference in relative intraocular pressure (IOP) measured by the SENSIMED Triggerfish (TF) contact lens in flat compared with 30° head-up sleeping positions in patients with progressive primary open-angle glaucoma or normotensive glaucoma, based on recent or recurrent disc haemorrhage.Prospective, randomised, cross-over, open-label comparative study.IOP was monitored for 24 hours using TF on two separate sessions. Patients were randomly assigned to sleep flat one night and 30° head-up the other. Outputs in arbitrary units were obtained. Sleep and wake periods were defined as 22:00-6:00 and 8:00-22:00, respectively. Mean TF values during sleep and wake periods and wake-sleep and sleep-wake slopes were calculated for each session. TF output signals were compared between positions.Twelve subjects completed the study. Significant mean positive slopes were noted during the sleep period for both positions (p0.01). No significant differences in the TF mean values were observed between positions (p=0.51). Six (54%) subjects had mean TF values significantly higher during the flat supine session, while four (36%) subjects had higher values during the head-up session. A significant increase in Goldmann IOP (p=0.001) and TF (p=0.02) measurements were observed after 24 hours of TF wear ('drift phenomenon').Sleep position affects IOP as measured by TF in some patients with progressive glaucoma. The upward drift in TF output detected in50% of the subjects requires further investigation to establish whether the increased output values over time are an artefact induced by the TF or a real change in IOP.NCT01351779.

Background Surgical patients with OSA are at increased risk for perioperative complications. Postoperative supplemental oxygen is commonly used, but it may contribute to respiratory depression in patients with OSA receiving opioids. The objective of the study is to investigate the effect of postoperative supplemental oxygen on arterial oxygen saturation (Sao 2 ), sleep respiratory events, and CO 2 level in patients with untreated OSA. Methods Consented patients with an apnea hypopnea index (AHI) > 5 events per hour on a preoperative polysomnography were randomized (1:1) to oxygen (O 2 group) or no oxygen (control group). The O 2 group received oxygen at 3 L/min via nasal prongs for three postoperative nights. The primary outcomes were polysomnographic parameters measuring Sao 2 , sleep respiratory events, and Pco 2 measured by transcutaneous CO 2 monitor (P tc CO 2 ) on nights 1 through 3. The intention-to-treat and per protocol analysis were completed. Results There were 123 patients randomized (O 2 group: n = 62; control group: n = 61). On night 3, the O 2 vs control group had a higher average Sao 2 (95.2% ± 3% vs 91.4% ± 4%, respectively; P P 2 group had a decreased AHI (median, 8.0; 25th-75th percentile, 2.1-19.9 vs median, 15.6; 25th-75th percentile, 9.5-45.8, respectively; P = .016), hypopnea index ( P P = .026) and a shortened longest apnea hypopnea duration ( P = .002). Although time percentage with P tc CO 2 ≥ 55 mm Hg ≥ 10% on postoperative night 1, 2, or 3 was found in 11.4% patients, there was no difference in P tc CO 2 between the groups. Conclusions Postoperative supplemental oxygen was found to improve oxygenation and decrease the AHI without increasing the duration of apnea-hypopnea event or P tc CO 2 level. A small number of patients had significant CO 2 retention while receiving supplemental oxygen. Trial Registry ClinicalTrials.gov; No.: NCT01552304; URL: www.clinicaltrials.gov

Introduction Solriamfetol (formerly JZP-110), a dopamine and norepinephrine reuptake inhibitor, has been approved in the United States to improve wakefulness in adults with excessive daytime sleepiness (EDS) associated with narcolepsy (75–150 mg) or obstructive sleep apnoea (OSA; 37.5–150 mg). A Marketing Authorisation Application for these indications is under review with the European Medicines Agency. This phase 3 study assessed safety and efficacy of solriamfetol in participants with narcolepsy types 1 and 2 (NT1/2).1 Methods In this 12-week, double-blind, randomised, placebo-controlled study, participants with or without cataplexy were randomised to solriamfetol 75 mg, 150 mg, 300 mg, or placebo. Eligibility criteria: NT1/2 diagnosis; mean sleep latency Results 236 participants received ≥1 dose of solriamfetol (67.2% female; 80.2% white). Baseline MWT mean sleep latency: 7.5 minutes; baseline ESS score: 17.2. Solriamfetol significantly increased MWT sleep latency at week 12 (P Discussion Solriamfetol improved wakefulness and reduced EDS in participants with NT1/2. Most AEs were mild to moderate. Support Jazz Pharmaceuticals. Reference Thorpy MJ, et al. Ann Neurol 2019;85(3):359–370.

Introduction Solriamfetol (formerly JZP-110), a dopamine and norepinephrine reuptake inhibitor, has been approved in the United States to improve wakefulness in adults with excessive daytime sleepiness (EDS) associated with narcolepsy (75–150 mg) or obstructive sleep apnoea (OSA; 37.5–150 mg). A Marketing Authorisation Application for these indications is under review with the European Medicines Agency. This study evaluated the long-term safety and efficacy of solriamfetol. Methods Participants with EDS associated with narcolepsy or OSA who completed prior solriamfetol studies initiated open-label treatment with a 2-week titration phase followed by a maintenance phase of ≤50 weeks. A 2-week, placebo-controlled, randomised withdrawal (RW) phase was conducted after 6 months. Change from beginning to end of the RW phase in Epworth Sleepiness Scale (ESS) was the primary endpoint; Patient and Clinician Global Impression of Change (PGI-C and CGI-C, respectively) were secondary endpoints. Results Safety population comprised 643 participants (226 narcolepsy; 417 OSA); 280 participants (141 placebo; 139 solriamfetol) comprised the RW modified intent-to-treat population. A total of 458 participants (71%) completed the study. Maintenance of efficacy in this 1-year study was demonstrated on the ESS, PGI-C, and CGI-C. Least squares mean change from the beginning to the end of the RW phase in ESS score was 5.3 versus 1.6 in participants randomised to placebo or solriamfetol, respectively (P Discussion These results demonstrate the long-term efficacy of solriamfetol for EDS in participants with narcolepsy or OSA. Safety profile following long-term administration was consistent with prior solriamfetol studies. Support Jazz Pharmaceuticals.

Study Objectives To evaluate long-term safety and maintenance of efficacy of solriamfetol treatment for excessive daytime sleepiness in narcolepsy and obstructive sleep apnea (OSA). Methods Participants with narcolepsy or OSA who completed a prior solriamfetol study were eligible. A 2-week titration period was followed by a maintenance phase (up to 50 weeks). Efficacy was assessed by Epworth Sleepiness Scale (ESS) and Patient and Clinical Global Impression of Change (PGI-C and CGI-C, respectively). After approximately 6 months of treatment, a subgroup entered a 2-week placebo-controlled randomized withdrawal (RW) phase. Change in ESS from beginning to end of the RW phase was the primary endpoint; PGI-C and CGI-C were secondary endpoints. Safety was assessed throughout the study. Results In the maintenance phase, solriamfetol-treated participants demonstrated clinically meaningful improvements on ESS, PGI-C, and CGI-C. In the RW phase, least squares mean change on ESS was 1.6 in participants continuing solriamfetol versus 5.3 in participants switched to placebo (p < .0001). For both secondary endpoints, higher percentages of participants receiving placebo were reported as worse at the end of the RW phase versus solriamfetol (p < .0001). Common treatment-emergent adverse events (TEAEs) with solriamfetol were headache, nausea, nasopharyngitis, insomnia, dry mouth, anxiety, decreased appetite, and upper respiratory tract infection; 27 (4.2%) participants experienced at least one serious TEAE, and 61 (9.5%) withdrew because of TEAEs. Conclusions This study demonstrated long-term maintenance of efficacy of solriamfetol under open-label and double-blind, placebo-controlled conditions. Safety profile of solriamfetol was consistent with previous 12-week studies; no new safety concerns were identified. Trial Registration NCT02348632

Introduction: Solriamfetol (JZP-110), a selective dopamine and norepinephrine reuptake inhibitor, was effective in treating excessive daytime sleepiness (EDS) in narcolepsy and obstructive sleep apnea (OSA) in phase 3 studies. Aims and Objectives: To evaluate long-term safety and efficacy of solriamfetol for EDS in narcolepsy and OSA. Methods: Participants who completed prior solriamfetol studies initiated open-label (OL) solriamfetol with a 2-wk titration followed by a maintenance phase of ≤50 wk. A 2-wk placebo-controlled randomized withdrawal (RW) phase began after 6 mo. Change in Epworth Sleepiness Scale (ESS) during RW was the primary endpoint. Patient and Clinician Global Impression of Change (PGI-C and CGI-C, respectively) were secondary endpoints. Results: The safety population comprised 643 participants (226 narcolepsy; 417 OSA); 280 participants (141 placebo; 139 solriamfetol) comprised the RW modified intent-to-treat population. At RW end, least squares mean change in ESS score for placebo vs solriamfetol was 5.3 vs 1.6 (P Conclusions: These results demonstrate long-term efficacy and safety of solriamfetol for EDS in narcolepsy or OSA.

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.

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.