1161 Tasimelteon Shows Persistence Of Efficacy In Improving Sleep Disturbances In Patients With Smith-Magenis Syndrome (SMS) In Open-Label Extension Study

Abstract Introduction Smith-Magenis Syndrome (SMS) is a rare (1/15,000 - 25,000 births) neurodevelopmental disorder resulting from an interstitial deletion of chromosome 17p11.2, or from a point mutation in the RAI1 gene. Severe sleep disorder is almost universal in patients with SMS and poses a significant challenge to patients and their families. Tasimelteon improved sleep symptoms in a randomized, double-blind, two-period, crossover study; and here we show that this effect persists for up to four years in an open-label extension. To our knowledge, this is the largest interventional study of SMS patients to date. Methods Following the 4-week crossover study, all eligible participants had the option to enroll in an open-label extension. 31/39 (79.4%) of all individuals who participated in the efficacy study have continued on tasimelteon treatment. Participants in the open-label extension provided daily diary sleep quality (DDSQ), and daily diary total sleep time (DDTST) measures via parental post sleep questionnaire and characterized behavior using the Aberrant Behavior Checklist (ABC). Results In the open-label extension, tasimelteon continued to show improvement in the primary endpoints of 50% worst sleep quality (mean = 0.7, SD = 0.94) and 50% worst total nighttime sleep duration (mean = 53.3, SD = 59.01) when compared to baseline. Tasimelteon also improved overall sleep quality (mean=0.7, SD=0.83) and overall total nighttime sleep duration (mean = 51.9, SD=53.03). ABC scores also improved with tasimelteon (mean= -16.3, SD = 15.82). Conclusion Tasimelteon continues to demonstrate persistence in efficacy (longest approximately 4 years) with similar magnitudes observed in the 4-week crossover study for sleep quality and total sleep time. Interestingly, daytime behavior also demonstrates long-term improvement in patients with SMS treated with tasimelteon. These results further confirm tasimelteon as a novel therapy for the treatment of sleep disorders in patients with SMS and may provide benefit for behavioral symptoms. Support This work was supported by Vanda Pharmaceuticals Inc.

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Tasimelteon safely and effectively improves sleep in Smith–Magenis syndrome: a double-blind randomized trial followed by an open-label extension

Genetics in Medicine ◽

10.1038/s41436-021-01282-y ◽

2021 ◽

Author(s):

Christos M. Polymeropoulos ◽

Justin Brooks ◽

Emily L. Czeisler ◽

Michaela A. Fisher ◽

Mary M. Gibson ◽

...

Keyword(s):

Sleep Quality ◽

Crossover Study ◽

Total Sleep Time ◽

Sleep Time ◽

Open Label ◽

Double Blind ◽

Open Label Study ◽

Label Study ◽

Sleep Complaints ◽

Open Label Extension

Abstract Purpose To assess the efficacy of tasimelteon to improve sleep in Smith–Magenis syndrome (SMS). Methods A 9-week, double-blind, randomized, two-period crossover study was conducted at four US clinical centers. Genetically confirmed patients with SMS, aged 3 to 39, with sleep complaints participated in the study. Patients were assigned to treatment with tasimelteon or placebo in a 4-week crossover study with a 1-week washout between treatments. Eligible patients participated in an open-label study and were followed for >3 months. Results Improvement of sleep quality (DDSQ50) and total sleep time (DDTST50) on the worst 50% of nights were primary endpoints. Secondary measures included actigraphy and behavioral parameters. Over three years, 52 patients were screened, and 25 patients completed the randomized portion of the study. DDSQ50 significantly improved over placebo (0.4, p = 0.0139), and DDTST50 also improved (18.5 minutes, p = 0.0556). Average sleep quality (0.3, p = 0.0155) and actigraphy-based total sleep time (21.1 minutes, p = 0.0134) improved significantly, consistent with the primary outcomes. Patients treated for ≥90 days in the open-label study showed persistent efficacy. Adverse events were similar between placebo and tasimelteon. Conclusion Tasimelteon safely and effectively improved sleep in SMS.

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Personality Traits and Insomnia Symptoms in Shift Workers

Frontiers in Psychology ◽

10.3389/fpsyg.2021.689741 ◽

2021 ◽

Vol 12 ◽

Author(s):

Brigitte Holzinger ◽

Lucille Mayer ◽

Gerhard Klösch

Keyword(s):

Sleep Quality ◽

Personality Traits ◽

Sleep Duration ◽

Total Sleep Time ◽

Sleep Time ◽

Work Schedule ◽

Shift Workers ◽

Time In Bed ◽

Shift Schedules ◽

Insomnia Symptoms

The discrepancy between natural sleep-wake rhythm and actual sleep times in shift workers can cause sleep loss and negative daytime consequences. Irregular shift schedules do not follow a fixed structure and change frequently, which makes them particularly harmful and makes affected individuals more susceptible to insomnia. The present study compares insomnia symptoms of non-shift workers, regular shift workers, and irregular shift workers and takes into account the moderating role of the Big Five personality traits and levels of perfectionism. Employees of an Austrian railway company completed an online survey assessing shift schedules, sleep quality and duration, daytime sleepiness, and personality traits. A total of 305 participants, of whom 111 were non-shift workers, 60 regular shift workers, and 134 irregular shift workers, made up the final sample. Irregular shift workers achieved significantly worse scores than one or both of the other groups in time in bed, total sleep time, sleep efficiency, sleep duration, sleep quality, sleep latency, and the number of awakenings. However, the values of the irregular shifts workers are still in the average range and do not indicate clinical insomnia. Participants working regular shifts reported the best sleep quality and longest sleep duration and showed the least nocturnal awakenings, possibly due to higher conscientiousness- and lower neuroticism scores in this group. Agreeableness increased the effect of work schedule on total sleep time while decreasing its effect on the amount of sleep medication taken. Perfectionism increased the effect of work schedule on time in bed and total sleep time. Generalization of results is limited due to the high percentage of males in the sample and using self-report measures only.

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1092 Attention-deficit/hyperactivity Disorder Symptoms And Sleep Characteristics Within A Seasonal Affective Disorder Spectrum

SLEEP ◽

10.1093/sleep/zsaa056.1087 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A415-A416

Author(s):

K N Kim ◽

D L Wescott ◽

P L Franzen ◽

B P Hasler ◽

K A Roecklein

Keyword(s):

Sleep Quality ◽

Sleep Duration ◽

Adhd Symptom ◽

Symptom Severity ◽

Daytime Sleepiness ◽

Total Sleep Time ◽

Sleep Time ◽

Sleep Onset Latency ◽

Adhd Symptoms ◽

Depression Severity

Abstract Introduction Seasonal affective disorder (SAD) increases risk for attention-deficit/hyperactivity disorder (ADHD), although the mechanism linking SAD and ADHD is unknown. Prior research has identified insomnia and delayed sleep phase in both ADHD and SAD. We hypothesized that sleep duration and timing in SAD would be associated with the severity of ADHD symptoms. Methods Adults with SAD (n = 45) and subsyndromal SAD (S-SAD; n = 18) aged 19-66 years from Pittsburgh, PA., were assessed for ADHD symptoms, self-report sleep quality, depression severity, and daytime sleepiness in the Winter. Participants wore an Actiwatch for 4-14 days, from which we calculated sleep-onset latency, total sleep time, sleep midpoint, and sleep efficiency. We conducted a hierarchical multivariate linear regression to determine if sleep characteristics predict ADHD symptom severity in our sample while controlling for depressive symptoms. Age and gender were added in Step 1, seasonal depression severity in Step 2, actigraphy-based total sleep time, sleep onset latency, midpoint, and efficiency in Step 3, and self-reported sleep quality and daytime sleepiness in Step 4. Results Participants mostly scored in the “likely” or “highly likely” ADHD range (87.30%, n=55), higher than the national prevalence rate (4.4%). When controlling for age, gender, and depression severity, only shorter actigraphy-based total sleep time was associated with higher ADHD symptom severity (β=-0.30, p<0.05). However, when self-reported sleep quality and daytime sleepiness were added as predictors, total sleep time was no longer a statistically-significant predictor of ADHD symptom severity and only daytime sleepiness predicted ADHD symptom severity (β=0.31, p<0.05). Conclusion Our results suggest that individuals with SAD who experience daytime sleepiness and/or possibly shorter actigraphy-based sleep duration experience higher ADHD symptom severity. Treatments like Trans-C or CBT-I to improve daytime sleepiness and sleep duration may be indicated for SAD patients who present with comorbid ADHD symptoms. Support NIMH K.A.R. MH103303

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Sleep maturation influences cognitive development of preterm toddlers

Scientific Reports ◽

10.1038/s41598-021-95495-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Akiko Ando ◽

Hidenobu Ohta ◽

Yuko Yoshimura ◽

Machiko Nakagawa ◽

Yoko Asaka ◽

...

Keyword(s):

Cognitive Development ◽

Sleep Duration ◽

Sleep Time ◽

Brain Maturation ◽

Sleep Diary ◽

Sleep Regulation ◽

Wake Time ◽

Daytime Nap ◽

Nighttime Sleep ◽

The Relationship

AbstractOur recent study on full-term toddlers demonstrated that daytime nap properties affect the distribution ratio between nap and nighttime sleep duration in total sleep time but does not affect the overall total amount of daily sleep time. However, there is still no clear scientific consensus as to whether the ratio between naps and nighttime sleep or just daily total sleep duration itself is more important for healthy child development. In the current study, to gain an answer to this question, we examined the relationship between the sleep properties and the cognitive development of toddlers born prematurely using actigraphy and the Kyoto scale of psychological development (KSPD) test. 101 premature toddlers of approximately 1.5 years of age were recruited for the study. Actigraphy units were attached to their waist with an adjustable elastic belt for 7 consecutive days and a child sleep diary was completed by their parents. In the study, we found no significant correlation between either nap or nighttime sleep duration and cognitive development of the preterm toddlers. In contrast, we found that stable daily wake time was significantly associated with better cognitive development, suggesting that sleep regulation may contribute to the brain maturation of preterm toddlers.

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Gender differences in BaYaka forager sleep-wake patterns in forest and village contexts

Scientific Reports ◽

10.1038/s41598-021-92816-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Erica Kilius ◽

David R. Samson ◽

Sheina Lew-Levy ◽

Mallika S. Sarma ◽

Ujas A. Patel ◽

...

Keyword(s):

Sleep Quality ◽

Total Sleep Time ◽

Sleep Time ◽

Small Scale ◽

Cultural Variation ◽

Sleep Patterns ◽

Economic Activities ◽

Mixed Effect ◽

Wake Patterns ◽

The Republic

AbstractSleep studies in small-scale subsistence societies have broadened our understanding of cross-cultural sleep patterns, revealing the flexibility of human sleep. We examined sleep biology among BaYaka foragers from the Republic of Congo who move between environmentally similar but socio-ecologically distinct locations to access seasonal resources. We analyzed the sleep–wake patterns of 51 individuals as they resided in a village location (n = 39) and a forest camp (n = 23) (362 nights total). Overall, BaYaka exhibited high sleep fragmentation (50.5) and short total sleep time (5.94 h), suggestive of segmented sleep patterns. Sleep duration did not differ between locations, although poorer sleep quality was exhibited in the village. Linear mixed effect models demonstrated that women’s sleep differed significantly from men’s in the forest, with longer total sleep time (β ± SE = − 0.22 ± 0.09, confidence interval (CI) = [− 0.4, − 0.03]), and higher sleep quality (efficiency; β ± SE = − 0.24 ± 0.09, CI = [− 0.42, − 0.05]). These findings may be due to gender-specific social and economic activities. Circadian rhythms were consistent between locations, with women exhibiting stronger circadian stability. We highlight the importance of considering intra-cultural variation in sleep–wake patterns when taking sleep research into the field.

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The Relationships Between Training Load, Type of Sport, and Sleep Among High-Level Adolescent Athletes

International Journal of Sports Physiology and Performance ◽

10.1123/ijspp.2020-0463 ◽

2020 ◽

pp. 1-10

Author(s):

Anis Aloulou ◽

Francois Duforez ◽

Damien Léger ◽

Quentin De Larochelambert ◽

Mathieu Nedelec

Keyword(s):

Sleep Quality ◽

Muscle Soreness ◽

Total Sleep Time ◽

Sleep Time ◽

Training Load ◽

Academic Environment ◽

Adolescent Athletes ◽

Daily Training ◽

High Level ◽

Age And Sex

Purpose: To evaluate the effects of sporting activities, training loads, and athletes’ characteristics on sleep among high-level adolescent athletes, in a controlled training and academic environment. Methods: A total of 128 high-level adolescent athletes (age = 15.2 [2.0] y), across 9 different sports, completed common sleep questionnaires and were monitored daily (7.3 [2.7] d) during a typical in-season training period. Sleep was analyzed using actigraphy and sleep diaries, whereas training load was evaluated using the session rating of perceived exertion, and muscle soreness and general fatigue were reported with the aid of visual analog scales. Separate linear mixed-effects models were fitted, including the athlete as a random effect and the following variables as fixed effects: the sport practiced (categorical predictor), daily training load, age, and sex. Different models were used to compare sleep variables among sports and to assess the influence of training load, age, and sex. Results: The mean total sleep time was 7.1 (0.7) hours. Swimmers presented increased sleep fragmentation, training loads, perceived muscle soreness, and general fatigue compared with athletes who engaged in other sports. Independent of any sport-specific effects, a higher daily training load induced an earlier bedtime and reduced total sleep time and perceived sleep quality, with higher sleep fragmentation. Moreover, female athletes experienced increased total sleep time and worse sleep quality in response to stress compared with those in males. Conclusion: In a controlled training and academic environment, high-level adolescent athletes did not achieve the recommended sleep duration. Impaired sleep quality and quantity could be partially explained by increased training loads.

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0409 The Efficacy of Afternoon-Evening Sleep Following Night Shifts on Sleep and Alertness in Nurses with Rotating Shift Work Schedule: Real World Data

SLEEP ◽

10.1093/sleep/zsaa056.406 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A156-A157

Author(s):

J Kim ◽

S Han ◽

S Kim ◽

J Duffy

Keyword(s):

Sleep Duration ◽

Shift Work ◽

Total Sleep Time ◽

Sleep Time ◽

Hospital Nurses ◽

Sleep Timing ◽

Time In Bed ◽

Shift Schedules ◽

Sleep Schedule ◽

Night Shifts

Abstract Introduction The aim of this study was to investigate the efficacy of changing sleep timing to afternoon-evening following nightshifts in hospital nurses with three rapid rotating shift schedules. Methods Hospital nurses with three rotating shift schedules were enrolled for a 1-month pre-intervention and a 1-month intervention study. During the Intervention, sleep timing following nightshifts was directed to afternoon-evening sleep for 8h time-in-bed (TIB) after 1 PM, and ad-lib sleep schedule for other shifts. Baseline and follow-up evaluation included sleep schedule, sleep duration, Epworth sleepiness scale (ESS), insomnia severity index (ISI) for each shift, Beck depression inventory (BDI), and Beck anxiety inventory (BAI). Sleep was assessed by sleep diary and actigraphy. Alertness during the night shift was evaluated using the Karolinska sleepiness scale (KSS) in the beginning and at the end of the shift by texts sent to their cell phones. The participants were asked to give feedback and a willingness to continue this intervention. Results A total of 26 subjects (30.7±8.5years, 25 female) finished the study among 29 nurses who participated in the study. The shift work was 6.5±8.0years. The mean morningness-eveningness scale was 42.1±8.0(31-62). TIB following nightshifts were 379.9±91.2 and 478.4±48.7 min for preintervention and intervention, respectively (p=0.001). Total sleep time (TST) was 328.0±91.0 vs. 361.0±70.4min, respectively following nightshifts (p=0.187, Cohen’s drm = 0.467). BDI, BAI, ESS, and ISI were significantly improved after the intervention. 60.7% and 49% of the participants reported improved alertness, and work efficiency during the nightshift. 17.9% and 42.9% of the participants reported increased sleep duration, and improved sleep quality after nightshift, respectively. Only eight participants were willing to continue the afternoon-evening sleep schedule following night shifts. KSS was not different between pre-intervention and intervention. Conclusion The afternoon-evening sleep schedule modestly increased total sleep time following nightshift. The overall mood, sleepiness and insomnia scale improved after the intervention although the alertness assessed by KSS failed to show the difference. The individual difference should be considered for applying afternoon-evening sleep for rapid rotating shift schedules. Support 2018 Research award grants from the Korean sleep research society and NRF-2019R1A2C1090643 funded by the Korean national research foundation

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Testing the contiguity of the sleep and fatigue relationship: a daily diary study

SLEEP ◽

10.1093/sleep/zsaa252 ◽

2020 ◽

Author(s):

Andrea L Harris ◽

Nicole E Carmona ◽

Taryn G Moss ◽

Colleen E Carney

Keyword(s):

Sleep Quality ◽

Hierarchical Linear Modeling ◽

Total Sleep Time ◽

Sleep Time ◽

Cognitive Factors ◽

Sleep Diary ◽

Poor Sleep ◽

Daily Diary Study ◽

Insomnia Disorder ◽

The Relationship

Abstract Study Objectives There is mixed evidence for the relationship between poor sleep and daytime fatigue, and some have suggested that fatigue is simply caused by lack of sleep. Although retrospective measures of insomnia and fatigue tend to correlate, other studies fail to demonstrate a link between objectively disturbed sleep and fatigue. The current study prospectively explored the relationship between sleep and fatigue among those with and without insomnia disorder. Methods Participants meeting Research Diagnostic Criteria for insomnia disorder (n = 33) or normal sleepers (n = 32) completed the Consensus Sleep Diary (CSD) and daily fatigue ratings for 2 weeks. Baseline questionnaires evaluated cognitive factors including unhelpful beliefs about sleep and rumination about fatigue. Hierarchical linear modeling tested the within- and between-participant relationships between sleep quality, total sleep time, and daily fatigue ratings. Mediation analyses tested if cognitive factors mediated the relationship between insomnia and fatigue. Results Self-reported nightly sleep quality significantly predicted subsequent daily fatigue ratings. Total sleep time was a significant predictor of fatigue within, but not between, participants. Unhelpful sleep beliefs and rumination about fatigue mediated the relationship between insomnia and fatigue reporting. Conclusions The results suggest that perception of sleep plays an important role in predicting reports of daytime fatigue. These findings could be used in treatment to help shift the focus away from total sleep times, and instead, focus on challenging maladaptive sleep-related cognitions to change fatigue perception.

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Sleep and Psychological Abuse Among Cohabiting Couples: A Pilot Study

Partner Abuse ◽

10.1891/1946-6560.8.4.347 ◽

2017 ◽

Vol 8 (4) ◽

pp. 347-360

Author(s):

Sharon Rose ◽

Linda Berg-Cross ◽

Nancy A. Crowell

Keyword(s):

Sleep Quality ◽

Relationship Satisfaction ◽

Sleep Deprivation ◽

Daytime Sleepiness ◽

Psychological Abuse ◽

Total Sleep Time ◽

Sleep Time ◽

Cohabiting Couples ◽

Survey Results ◽

The Relationship

This study explored the relationship between psychological abuse and sleep deprivation among nonclinical cohabiting couples. Thirty-one couples participated in completing a variety of sleep measures, a psychological abuse scale, and a relationship satisfaction survey. Results indicated a persistent relationship between everyday sleep deficits (sleep quality, daytime sleepiness, and self-reported total sleep time) and the perceived perpetration and felt victimization of psychological abuse. Overall, results were as hypothesized, but there were gender differences. Male psychological abuse victimization and perpetration were significantly related to sleep quality and daytime sleepiness, but for women, only sleep duration was predictive of felt victimization. The sleep variables were significantly related to women’s—but not men’s—reported relationship satisfaction. Overall, minimal sleep deprivation appears to be related to increased psychological abuse perpetration and victimization even among a normative population scoring outside the clinical range on these measures. Implications for prevention and treatment are discussed.

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Association Between Electroencephalogram-Derived Sleep Measures and the Change of Emotional Status Analyzed Using Voice Patterns: Observational Pilot Study

JMIR Formative Research ◽

10.2196/16880 ◽

2020 ◽

Vol 4 (6) ◽

pp. e16880

Author(s):

Hirotaka Miyashita ◽

Mitsuteru Nakamura ◽

Akiko Kishi Svensson ◽

Masahiro Nakamura ◽

Shinichi Tokuno ◽

...

Keyword(s):

Pilot Study ◽

Regression Coefficient ◽

Total Sleep Time ◽

Sleep Onset ◽

Sleep Time ◽

Sleep Onset Latency ◽

Inverse Association ◽

Onset Latency ◽

Emotional Status ◽

Nighttime Sleep

Background Measuring emotional status objectively is challenging, but voice pattern analysis has been reported to be useful in the study of emotion. Objective The purpose of this pilot study was to investigate the association between specific sleep measures and the change of emotional status based on voice patterns measured before and after nighttime sleep. Methods A total of 20 volunteers were recruited. Their objective sleep measures were obtained using a portable single-channel electroencephalogram system, and their emotional status was assessed using MIMOSYS, a smartphone app analyzing voice patterns. The study analyzed 73 sleep episodes from 18 participants for the association between the change of emotional status following nighttime sleep (Δvitality) and specific sleep measures. Results A significant association was identified between total sleep time and Δvitality (regression coefficient: 0.036, P=.008). A significant inverse association was also found between sleep onset latency and Δvitality (regression coefficient: –0.026, P=.001). There was no significant association between Δvitality and sleep efficiency or number of awakenings. Conclusions Total sleep time and sleep onset latency are significantly associated with Δvitality, which indicates a change of emotional status following nighttime sleep. This is the first study to report the association between the emotional status assessed using voice pattern and specific sleep measures.

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