bluuebunny/crossref_metadata_2025 huggingface dataset:
0401 Sleep Characteristic Differences During Early Postpartum in White and African American Women
Authors: Kishman E E , Sparks J R , Liu J , Castleberry L A , Cook J W , Youngstedt S D , Wang X
Published: May 2020

Introduction

In the general population, poor sleep quality and shorter sleep duration is associated with several adverse health outcomes. African American adults are more likely to report poorer sleep quality and shorter total sleep duration compared to White adults. However, there is limited information comparing sleep characteristics in White and African American women during postpartum, when many women experience reduced sleep quality. The purpose of this study was to compare sleep quality at 6-8 weeks postpartum in White and African American women.

Methods

White (n=84) and African American (n=37) women, who gave birth to a singleton at ≥ 37 weeks of gestation, completed the Pittsburg Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) at 6-8 weeks postpartum. The PSQI was used to assess global sleep quality, time in bed, and 7 components regarding sleep. The components included: Subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The ESS total score was used to assess daytime sleepiness.

Results

The global PSQI score was higher for African American women (8.8 ± 3.3, mean ± SD), indicating poorer sleep quality than White women (7.1 ± 3.0, p=.006). African American women had higher sleep latency and shorter sleep duration compared to White women (p=.0179 and p<.0001, respectively). Time in bed was not statistically different for African American women compared to White women (485.6 ± 143.7 and 530.8 ± 85 minutes/night, p=.08). No other components of the PSQI were significantly different between the two racial groups. African American women scored higher on the ESS than White women (8.9 ± 3.1, 6.6 ± 3.2, p=.0002) indicating greater daytime sleepiness.

Conclusion

These results suggest that African American women experience lower sleep quality and greater daytime sleepiness in early postpartum compared to White women.

Support

National Institute On Minority Health And Health Disparities of the National Institutes of Health under Award Number R21MD012740.
0403 Sleep Valuation: A Novel Construct and Questionnaire
Authors: Nielson S , Simmons Z , Kay D
Published: May 2020

Introduction

Sleep valuation, the relative worth of one’s own sleep, is an under-explored construct that could have implications on sleep health. This study sought to validate the Sleep Valuation Questionnaire (SVQ) and to explore demographic differences in sleep valuation.

Methods

Participants (N = 946) recruited through TurkPrime were stratified across age (18-99), race (50% White, 17% Black, and 8.33% for each American Indian, Asian, Pacific Islander, and other), Hispanic ethnicity (20%), gender (50/50 female/male), employment status (50% employed full time and 8.33% for each part time, homemaker, retired, student, temp worker. unemployed, and disabled), Participants completed a demographic survey, followed by the original 43 item SVQ completed twice. Iterated principal factoring with a Promax solution was used to identify the factor structure of the SVQ. Cronbach’s alpha and correlation analyses were also used to help identify items with poor reliability. Total sleep valuation, the sum of valid items on the SVQ, was used as the dependent variable in a multiple regression analysis. Age, gender, race, work status, socioeconomic status, educational level, marital status, and general health and mental health estimates served as independent variables.

Results

After removing items with weak factor loadings (<0.6), poor reliability, and weak face validity, the number of items were reduced to 10, which loaded on to 2 factors: Sleep Desire and Sleep Need. Those who cohabitate had lower SVQ scores than married individuals (p=0.04), full-time workers had higher SVQ scores than non-full-time workers (p=0.001), higher age was associated with lower SVQ scores (p<0.001), and higher general mental health was associated with lower SVQ scores (p<0.001).

Conclusion

This is the first study to explore how demographic variables relate to sleep valuation. The SVQ may help identify factors that contribute to sleep valuation and sleep valuation relates to sleep behavior, sleep health, and sleep treatment utilization.

Support

None
0407 Sleep, Stress, Cardiovascular, and Psychological Health in College Students
Authors: Reynolds A M , Mullins K M
Published: May 2020

Introduction

Epidemiological studies have long established that sleep factors, stress, and cardiovascular health are related. College students often struggle with the demands of college life, which leads to increased stress, symptoms of depression and anxiety, and poor sleep. The focus of the current study was to examine habitual sleep habits in college students, in association with psychological factors and physiological factors.

Methods

Participants included 51 undergraduate students (18 men, average age M=20.25 years, SD=1.78) who wore wrist actigraphs to measure their typical sleep habits. After one week, participants completed questionnaires about psychological symptoms (i.e., depression, anxiety, and stress; Depression Anxiety Stress Scale, DASS-21) and subjective physiological symptoms (i.e., fatigue; Multidimensional Assessment of Fatigue Scale, MAF). Blood pressure and heart rate were measured using a wrist cuff.

Results

Overall total sleep time was 6.59 hours and sleep efficiency was 82.55%. Pearson correlational analyses revealed a negative moderate association between sleep efficiency and diastolic blood pressure (r(49) = -.318, p = .024). Global PSQI scores were moderately associated with stress (r(49) = .419, p = .002). MAF Global Fatigue Index scores revealed positive associations with depression (r(49) = .344, p =.014), anxiety (r(49) = .474, p<.001), and stress (r(49) = .620 p<.001). Heart rate was positively associated with depressive symptoms r(49) = .296, p= .035), stress symptoms r(49) = .447, p= .001), and fatigue r(49) = .456, p= .001).

Conclusion

As expected, college students’ sleep was short in duration and poor in efficiency. Sleep factors, cardiovascular factors, psychological factors, and stress were all related, demonstrating the importance of sleep on physiological and psychological health. More research should be conducted to further examine the relationships and directionality between sleep, psychological factors, and stress as there may be underlying mechanisms important for cardiovascular health.

Support

None.
0409 The Efficacy of Afternoon-Evening Sleep Following Night Shifts on Sleep and Alertness in Nurses with Rotating Shift Work Schedule: Real World Data
Authors: Kim J , Han S , Kim S , Duffy J
Published: May 2020

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
0418 Effect of Acute Administration of DORA-12 on Sleep Impairment in the Aged PS19 Mouse Model of Tauopathy
Authors: Kam K , Vetter M , Berryman N , Varga A
Published: May 2020

Introduction

Aged PS19 mice (MAPT P301S), a mouse model of tauopathy and neurodegeneration, display reduced NREM and REM sleep starting around 8-9 months before death around 12 months. Here, we tested the acute effect of a dual orexin receptor antagonist (DORA-12) on sleep in 11 mice (5 male, 6 female) at 10.3±1.8 months.

Methods

Two consecutive 24-hour recordings (12/12hr L:D cycle) were scored semi-automatically for non-REM sleep, REM sleep, and wake in mice implanted with EEG/EMG. Mice were treated with either vehicle (day 1) or 100mg/kg of DORA-12 (day 2) by oral gavage at both ZT0 and ZT9.

Results

After the first dose at ZT0, both latency to the first NREM sleep episode (paired t-test p=0.002) and to the first REM sleep episode (paired t-test p=0.005) was significantly shorter with DORA-12 (NREM: 20.8±17.8 min.; REM: 23.5±21.2 min.) compared to vehicle (NREM: 49.2±22.3 min.; REM: 127.0±93.3 min.). There was no difference in NREM or REM sleep latency observed after the second dose at ZT9. DORA-12 treatment increased NREM duration across the 24hr period (DORA-12: 664±52 min.; Veh: 601±54 min., paired t-test p=0.007) and also after the 2nd dose (DORA-12: 311±65 min.; Veh: 263±84 min., paired t-test p=0.009). DORA-12 treatment also increased REM duration across 24hrs (DORA-12: 61±30 min.; Veh: 48±29 min., paired t-test p=0.014) but not after the 2nd dose alone (DORA-12: 22±14 min.; Veh: 20±15 min., paired t-test p=0.388). Notably in both vehicle and DORA-12 conditions, we observed apparent dream enactment behavior including mastication, paw grasp, and fore limb extension during REM in 3 of 11 PS19 mice (all male), not typically observed in younger PS19 or age-matched non-transgenic mice, suggestive of a possible REM behavior disorder (RBD) phenotype. Wake-like behaviors occurred during theta-dominant EEG but with an EMG amplitude >4SD the preceding NREM sleep baseline for at least > 1sec.

Conclusion

In aged PS19 mice, DORA-12 was found to decrease the latency to NREM and REM after the first dose while also increasing NREM and REM duration across the entire 24hr recording period. We also capture a heretofore undescribed RBD-like phenotype in aged PS19 tauopathy mice.

Support

Merck MISP
0429 Chronic Sleep Disturbance Causes Cognitive Impairment and Alzheimer’S Disease-Like Neuropathology
Authors: Le W
Published: May 2020

Introduction

Sleep disturbance is among the most common clinical problem and possesses a significant concern for the geriatric population. Recently, increasing evidence has indicated that disturbed sleep may not only affect neuropsychological functions, but also contribute to the cognitive impairment and, therefore, significantly increase dementia risk.

Methods

In the present study, we examined the potential impacts of chronic sleep deprivation (SD) on learning-memory and AD-related pathologies in AβPPswe/PS1ΔE9 transgenic (TG) mice and their wild-type (WT) littermates.

Results

Our results indicated that mice (both TG and WT) exposed to 2-month SD showed an altered amyloid-βprotein precursor processing, elevated level of phosphorylated tau protein, and impaired cognitive performance as compared to non-sleep deprivation (NSD) controls. Moreover, the SD-treated TG mice exhibited more amyloid-β1-42 production and developed more senile plaques in the cortex and hippocampus than NSD-treated TG mice. In addition, SD caused a striking neuronal mitochondrial damage, caspase cascade activation, and neuronal apoptosis in the hippocampus of both TG and WT mice. More importantly, all these behavioral, neuropathological, and biochemical changes induced by chronic SD were long lasting and were irreversible during a 3-month normal housing condition.

Conclusion

Collectively, these results indicate that chronic SD impairs learning and memory, exacerbates AD pathologies, and aggravates the mitochondria-mediated neuronal apoptosis in a long-lasting manner.

Support

Our findings provide important experimental evidence to prove that chronic sleep disturbance is a risk factor for AD.
0437 Characterizing the Impact of EEG Referencing on Sleep Spindle and Slow Oscillation Analyses
Authors: He M , Prerau M J , Dimitrov T S
Published: May 2020

Introduction

The impact of EEG referencing on sleep oscillations, such as spindles and slow oscillations, is largely overlooked across studies. While it is recognized that a topographic head plot of EEG activity does not reflect the true location of the underlying cortical activity, spatial distributions, as well as spectral properties and morphology of EEG oscillations can change dramatically as a function of referencing scheme. It is therefore vital to understand the impact of referencing when drawing inferences about the nature of EEG sleep oscillations. In this study, we use MRI structural data to construct subject-specific forward models of EEG signals. Using these models, we can simulate cortical activity and observe its true representation on the scalp. In particular, we simulate spindles and slow wave oscillations and examine how referencing affects topography, spectral power, and phase of oscillations.

Methods

High-density EEG (Brain Vision, 64-channel) polysomnography was performed on 9 healthy young subjects. 3T structural MRI scans were acquired and forward models were built in MNE-Python using 3-shell Boundary Element Models (BEM) based on individual anatomical details processed with Freesurfer. Simulations of various sleep spindle and slow oscillation dynamics were projected to the sensor space. Different referencing schemes (common average, Laplacian, linked-mastoid) were then applied to the experimental and simulated data and analyzed for effects on time-frequency characteristics of sleep oscillations.

Results

Analyses of experimental data showed distinct reference-based differences in topographical distribution of spectral power and phase of oscillations. Simulated data revealed many scenarios in which the spatial distribution of activity the EEG sensor space poorly represented the true location of the underlying source activity. Moreover, there were alterations to the spatial spread and envelope form of sleep spindle events under different referencing schemes despite from identical source activities.

Conclusion

This study shows that spindle and slow oscillation activity is highly variable across referencing schemes and that EEG topographical plots on the scalp may poorly represent cortical activity locations. It is thus vital to consider the choice of referencing when quantifying characteristics of sleep EEG oscillations.

Support

This work was supported by R01 NS-096177.
0441 An Automatic Sleep Scoring System Based on Ensemble Convolutional Neural Network and Spectrogram of Sleep Physiological Signal
Authors: Kuo C , Chen G
Published: May 2020

Introduction

Manual sleep stage scoring is time consuming and subjective. Therefore, several studies focused on developing automated sleep scoring algorithms. The previously reported the automatic sleep scoring have been develop usually using small dataset, which less than 100 subjects. In this study, an automatic sleep scoring system based on ensemble convolutional neural network (ensemble-CNN) and spectrogram of sleep physiological signal was proposed and evaluated using a large dataset with sleep disorder.

Methods

The spectrograms were computed from each 30-s EEG and EOG of 994 subjects from PhysioNet 2018 challenge dataset, using the continuous wavelet transform, which were fed into an ensemble-CNN classification for training. The ensemble-CNN contained five pretrained models, ResNet-101, Inception-v4, DenseNet-201, Xception, and NASNet models, because these models’ architectures are different which can learn different features from the spectrograms to obtain high accuracy. The probabilities of five models were averaged to decide the sleep stage for each spectrogram. After classifying sleep stage, a smoothing process was used for sleep continuity. Moreover, the total 80% data from PhysioNet dataset were randomly assigned to the training set, and the remaining data were assigned to the testing set.

Results

To validate the robustness of the proposed system, the validation procedure was repeated five times. The performance measures were averaged over the five runs. The overall agreement and kappa coefficient of the proposed method are 82% and 0.73, respectively. The sensitivity of the sleep stages of Wake, N1, N2, N3, and REM are 90.0%, 48.6%, 84.9%, 84.2%, and 81.9%, respectively.

Conclusion

The performance of the proposed method was achieved expert level, and it was noted that the ensemble-CNN is a promising solution for automatic sleep stage scoring. This method can assist clinical staff in reducing the time required for sleep stage scoring in the future.

Support

This work was supported by the Ministry of Science and Technology, Taiwan. (MOST 106-2218-E-035-013-MY2, 108-2221-E-035-064, and 108-2634-F-006-012).
0445 A Novel Algorithm for the Estimation of Sleep States Based on Breathing and Movement
Authors: Dietz-Terjung S , Martin A , Schöbel C
Published: May 2020

Introduction

We tested the diagnostic accuracy of the novel Nox BodySleep™ algorithm (Nox Medical, Iceland) for the estimation of sleep states from polygraphy (PG) sleep recordings based on features extracted from actigraphy and respiratory inductance plethysmography (RIP) belts. The algorithm automatically classifies epochs into three states, Wake, REM sleep and NonREM sleep. Validation was performed against polysomnography (PSG) in a sleep laboratory collective including patients with sleep disordered breathing (SBAS) and sleep related movements disorders.

Methods

Patients received PSG according to clinical routine. The recording was evaluated by the novel algorithm and the results were evaluated by descriptive statistics methods (IBM SPSS Statistics 25.0).

Results

We found a good Spearman correlation (r=0.8) and a bias of 11 minutes for the estimation of Total Sleep Time. Sleep Efficiency was also valued with a good Spearman correlation (r=0.7) and a bias of 1.6%. Wake phases were estimated with a F1 score of 0.64 while REM and Non-REM phases were evaluated with a F1 score of 0.73 and 0.82, respectively. Additionally, an overall accuracy of 0.8 and a Cohens kappa of 0.7 were found. Patients with sleep related movement disorders showed a slighly weaker correlation as patients with SBAS.

Conclusion

The algorithm shows a good diagnostic accuracy for the estimation of sleep states and significant sleep parameters. After validation on a larger patient collective, it could be used in the ambulatory and telemedical field to allow investigations comparable to the accuracy of a PSG.

Support

No support.
0454 Sleep Disruptive Cognitions in Deployment-Related Insomnia
Authors: Howell M , Mellman T
Published: May 2020

Introduction

Sleep disturbance is common following military deployment, and insomnia is associated with many adverse psychiatric and medical outcomes. Deployment to a threatening environment can engender nocturnal vigilance, which may be a salient feature of sleep disturbance in formerly deployed Veterans. Cognitive behavioral therapy for insomnia (CBTI) is an effective treatment; however, CBTI emphasizes targeting dysfunctional beliefs about sleep (DBAS) and generalized worries rather than vigilance. The goal of the present study was to investigate the role of vigilance, in relation to other potential types of sleep-interfering cognitions in formerly deployed Veterans with sleep disturbance.

Methods

Thirty-nine formerly deployed Veterans with disturbed sleep completed measures prior to an intervention. Insomnia was measured with the Insomnia Severity Index (ISI) and measures derived from actigraphy and morning sleep diaries administered for one week. Measures for sleep interfering cognitions included Dysfunctional Beliefs about Sleep (DBAS), the Penn State Worry Questionnaire (PSWQ), a measure of generalized worry, and the Fear of Loss of Vigilance (FLV) subscale of the Fear of Sleep Inventory (FOSI).

Results

All of the measures of sleep-interfering cognitions were significantly associated with ISI score. Generalized worries (PSWQ scores) were strongly and significantly correlated with both FLV and DBAS, which were not significantly correlated with each other. FOSI FLV explained 7.1% more variance in ISI score than DBAS alone (p = .04) while DBAS explained 23.1% additional variance in ISI score over FOSI FLV alone (p < .001).

Conclusion

It may be important to target both nocturnal vigilance and dysfunctional beliefs about sleep in the treatment of insomnia in formerly deployed Veterans.

Support

Supported by W81XWH-14-1-0066 from the Congressionally Directed Peer-Reviewed Medical Research Program of the Department of Defense.
0461 Blunted Baroreflex Sensitivity and Reduced Morning Parasympathetic Activity in Sleep-Onset Insomnia
Authors: Tsai H , Kuo T , Yang C
Published: May 2020

Introduction

Insomnia is a risk factor for hypertension and cardiovascular events, and this association is strongest for sleep-onset insomnia. However, little is known about insomnia on cardiovascular modulation, especially soon after morning awakening, the peak period of time for cardiovascular incidents. This study explored morning cardiovascular function in individuals with sleep-onset insomnia by analysing heart rate variability, blood pressure variability, and baroreflex sensitivity.

Methods

Sleep structure of the participants (15 good sleepers and 13 individuals with sleep-onset insomnia) was measured by laboratory polysomnography, followed by continuous recordings of the participant’s blood pressure and heart rate for 10 min in the morning.

Results

When compared to the good sleepers, the insomnia group showed significant reductions in total sleep time, a longer sleep-onset latency, and reduced sleep efficiency. The sleep structure, including durations of sleep stages, numbers of awakenings and arousal index did not differ between the groups. After morning awakening (averaged time: 12.33 ± 10.48 min), the shorter R-R intervals, lower total power, and lower high-frequency power of heart rate variability were observed among individuals with sleep-onset insomnia, compared with good sleepers. Elevated slopes of systolic and diastolic blood pressure, as well as lower baroreflex sensitivity, were also shown in the insomnia group. Indices of sympathetic activity, including low-frequency percentage of heart rate variability or low-frequency power of blood pressure variability, did not differ between the groups.

Conclusion

Weak vagal activity and blunted baroreflex sensitivity were evident among sleep-onset insomnia. These findings indicate difficulty in initiating sleep, without significant sleep fragmentation, can independently affect morning cardiovascular function. This study provides a possible link between sleep-onset insomnia and risk of cardiovascular events.

Support

N/A
0464 Sleep Continuity by Neighborhood: Are There Differences?
Authors: Giller J , Muench A , Grandner M A , D’Antonio B , Perlis M L
Published: May 2020

Introduction

To our knowledge, no prior work has been conducted on whether sleep continuity disturbance (e.g., SL; WASO; EMA, etc.) varies by neighborhood. While differences on these metrics have been found by, e.g., race and socioeconomic status, it may also be that sleep continuity disturbance varies relative to where one lives and works. Accordingly, an analysis was undertaken to assess whether regional differences exist with respect to sleep continuity disturbance (SCD).

Methods

The study utilized a cross-sectional group design in an archival/community dataset that was collected in the Philadelphia area (www.sleeplessinphilly.com). This dataset (n = 2840) was comprised of adults between 18 and 89 years of age with self-reported sleep complaints (63.4% female; 36.6% male; average age 38). Study subjects who endorsed >30 minutes on >3 days/week on SL, WASO & EMA were categorized by zip code and into four regional groups: Center City (n=258); South Philadelphia (n=103); North & Northeast Philadelphia (n=400) and West Philadelphia (n=345). Contingency analyses and ANOVAS were used to assess for regional group differences.

Results

It was found that SCD rates significantly differed by region. Differences in percent endorsement by region were as follows, SL:, 64.1% (Northeast/North), 63.5 (South), 56.3% (West Philadelphia), & 48.7% (Center City); WASO: 45% (Northeast/North), 40% (South), 36.5% (West Philly), & 32.4% (Center City); EMA: 46.4% (South); 43.7 (Northeast/North); 43.7 (West Philly); 43.1 (Center City).

Conclusion

The Northeast/North region of Philadelphia had the highest rates, and center city had the lowest rates of SCD for the early part of the night (SL & WASO). Early morning SCD was most common for “South Philly and least common for Center City. Analyses are on-going in relation to other regional differences (demographic, income, crime stats, etc.) and those found to vary by region will be assessed for their predictive value.

Support

No support was provided for this abstract
0467 Benefits of CBT-I for Women Veterans with and without PTSD
Authors: Carlson G C , Kelly M R , Josephson K , Mitchell M , Fiorentino L , McGowan S , Culver N , Kay M , Alessi C , Washington D L , Yano E , Martin J L
Published: May 2020

Introduction

A quarter of women Veterans (WVs) receiving VA healthcare meet diagnostic criteria for both insomnia disorder and posttraumatic stress disorder (PTSD). Cognitive Behavioral Therapy for Insomnia (CBT-I) is effective at improving sleep among individuals with comorbid psychiatric conditions; however, no studies have examined the impact of CBT-I in women with insomnia plus PTSD. The current analyses examined changes in sleep symptoms, quality of life (QoL), and mental health symptoms from pre- to post-CBT-I in WVs with and without PTSD.

Methods

This was a secondary analysis of 75 WVs with insomnia (32 with probable PTSD), who received CBT-I within a behavioral sleep intervention study (NCT02076165). Measures completed at baseline, posttreatment, and 3-month follow-up included: insomnia severity (Insomnia Severity Index, ISI), sleep quality (Pittsburgh Sleep Quality Index, PSQI), PTSD symptoms (PTSD Checklist-5, PCL-5; probable PTSD=total score ≥33), depressive symptoms (Patient Health Qestionnaire-9, PHQ-9), and mental and physical quality of life (Short Form Health Survey, SF-12). One sample T-tests examined changes in ISI, PSQI, PHQ-9, PCL-5, and SF-12 from baseline to posttreatment and baseline to follow-up. Two samples T-tests compared change scores in ISI, PSQI, PHQ-9, and SF-12 between participants with and without PTSD.

Results

There were significant improvements in ISI (p≤.001), PSQI (p≤.001), PHQ-9 (p≤.001), PCL-5 (p=.001), and SF-12 mental (p≤.001) and physical (p=.03) from baseline to posttreatment and 3-month follow-up (p≤.001-.01). There were no significant change score differences between WVs with and without PTSD from baseline to posttreatment (p=.06-.98) or 3-month follow-up (p=.09-.93).

Conclusion

CBT-I appears to be an effective treatment to improve insomnia symptoms among WVs with and without PTSD, and may reduce psychiatric symptoms as well. These findings suggest WVs with comorbid insomnia and PTSD benefit from CBT-I. The appropriate sequencing of CBT-I and PTSD treatments remains potentially important, but unstudied.

Support

VA/HSR&D IIR-HX002300; NIH/NHLBI K24HL14305; VA Office of Academic Affiliations through the Advanced Fellowship Programs in HSR&D and Women’s Health
0472 Do the Subjective Effects of Hypnotic Medications Result in Unblinding of Treatment Assignment in Hypnotic Randomized Clinical Trials?
Authors: McCall W V , Benca R M , Rumble M , Krystal A D
Published: May 2020

Introduction

Some hypnotic medications have obvious subjective effects, including therapeutic effects (i.e., anti-insomnia effects), and side effects (i.e., feelings of impairment/intoxication). Information is lacking regarding whether the subjective effects of hypnotics result in unblinding of treatment assignment (active drug versus placebo) in hypnotic randomized clinic trials (RCTs), thus undermining internal validity of study results. In response, we now report the ‘best guesses’ of clinical trial participants, versus study coordinators, versus study physicians in the study Reducing Suicidal Ideation Through Insomnia Treatment (REST-IT).

Methods

Eighty-nine of the 103 participants in the REST-IT study completed their ‘best guess’ regarding which randomized treatment they had been assigned. REST-IT was a blinded RCT, comparing zolpidem controlled release (CR) versus placebo at bedtime given over 8 weeks in adults with major depressive disorder who also had insomnia and suicidal ideation, and who also received open label fluoxetine. At the conclusion of study participation, the study participants, the study coordinators and the study physician each independently recorded their ‘best guess’ regarding which treatment arm the patient had been assigned. The study physicians and the study coordinators had access to the participants’ Insomnia Severity Index scores when the ‘best guess’ was made.

Results

Patients guessed correctly 58.4% of the time, coordinators 53.9% of the time, and physicians 49.4% of the time. The percentage guessed correctly did not differ significantly between groups. Physicians most often guessed placebo (56.2%) while study coordinators most often guessed zolpidem-CR (55.1%). Agreement between pairs of study participants with the study coordinators and the study physician was moderately high, with all kappa values 0.49- 0.57, and all kappa differences between zolpidem and placebo with p-values >0.8.

Conclusion

The blind was maintained in this RCT of zolpidem-CR versus placebo, especially for the physicians. Our results may not apply to other hypnotics or other RCT designs.

Support

NIMH MH095776, MH095780, MH95778
0473 Effectiveness and Safety of Lemborexant in Subjects Previously Treated with Placebo for 6 Months in SUNRISE-2
Authors: Yardley J , Inoue Y , Pinner K , Perdomo C , Filippov G , Kubota N , Moline M
Published: May 2020

Introduction

In SUNRISE-2 (NCT02952820; E2006-G000-303), while lemborexant (LEM) provided significant benefit versus placebo (PBO) on sleep-diary measurements over 6mo, some improvement was noted in PBO subjects. We report outcomes from PBO subjects rerandomized to LEM during the last 6mo of SUNRISE-2.

Methods

SUNRISE-2 was a randomized, double-blind, global phase 3 study in adults (≥18y) with insomnia disorder. Subjects received PBO or LEM (5mg [LEM5]; 10mg [LEM10]) for 6mo. PBO subjects were rerandomized to LEM for another 6mo; LEM subjects continued assigned treatment. Changes from 6mo baseline (calculated after PBO completion) in subjective sleep onset latency (sSOL), subjective sleep efficiency (sSE), and subjective wake after sleep onset (sWASO) are reported for rerandomized subjects.

Results

At study baseline for PBO subjects (n=318), median sSOL (min) was 55.9, mean (SD) sSE (%) and sWASO (min) were 61.3 (17.8) and 132.5 (80.2), respectively. The 6mo baseline values for rerandomized PBO-LEM5 (n=133) and PBO-LEM10 (n=125) subjects, respectively, were: median sSOL, 31.2, 34.3; mean (SD) sSE, 70.5 (20.2), 71.1 (18.0); mean (SD) sWASO, 105.1 (80.6), 100.1 (84.6). Median sSOL decreased from the 6mo baseline after 1mo (PBO-LEM5, −3.2; PBO-LEM10, −2.9) and 6mo (PBO-LEM5, −2.7; PBO-LEM10, −5.0). Mean (SD) sSE increased from the 6mo baseline after 1mo (PBO-LEM5, 3.9 [12.1]; PBO-LEM10, 3.5 [8.1]) and 6mo (PBO-LEM5, 3.9 [13.6]; PBO-LEM10, 4.5 [13.0]). Mean (SD) sWASO decreased after 1mo (PBO-LEM5, −8.5 [49.4]; PBO-LEM10, −5.7 [36.1]) and 6mo (PBO-LEM5, −8.2 [49.0]; PBO-LEM10, −10.0 [58.8]). Treatment-emergent adverse events incidence was similar during PBO (62.7%) and LEM treatment (PBO-LEM5, 54.9%; PBO-LEM10, 57.7%). Adverse events were consistent with those seen in the initial 6mo of treatment for patients originally randomized to LEM.

Conclusion

Rerandomization to LEM was associated with additional improvement in sleep outcomes following the PBO-related response. LEM benefit was evident after 1mo and was sustained throughout treatment. LEM was well tolerated.

Support

Eisai Inc.
0479 Sleep Onset and Sleep Maintenance Responder Profiles Over 12 Months of Treatment with Lemborexant: Results from SUNRISE-2
Authors: Zammit G , Yardley J , Pinner K , Moline M
Published: May 2020

Introduction

In addition to analyzing treatment response by comparing change from baseline (CFB) between active treatment and placebo (PBO), it is also informative to evaluate the percent of patients with a given magnitude of response. This can help establish the expected degree of improvement for patients, thereby helping to determine treatment success.

Methods

SUNRISE-2 (NCT02952820; E2006-G000-303) was a randomized, double-blind, global phase 3 study of lemborexant (LEM) in adults (≥18y) with insomnia disorder. Subjects received PBO or LEM (5mg [LEM5]; 10mg [LEM10]) for 6mo. LEM subjects continued their original dose, while PBO subjects were rerandomized to LEM for another 6mo (not reported here). Responder profiles were constructed separately for patient-reported, sleep diary-based subjective sleep onset and sleep maintenance based on the cumulative proportion of subjects with CFBs in 10-minute increments for subjective sleep onset latency (sSOL) or subjective wake after sleep onset (sWASO), respectively. The proportion was based on number of subjects with baseline data (denominator) and data available at time of visit; study dropouts were considered nonresponders.

Results

Baseline values were similar (median sSOL [min]: PBO, 55.9; LEM5, 53.6; LEM10, 55.7; mean[SD] sWASO [min]: PBO, 132.5[80.2]; LEM5, 132.8[82.5]; LEM10, 136.8[87.4]). At 6mo, a higher percentage of subjects with CFB of ≥20min in sSOL was observed with LEM versus PBO (PBO, 30.4%; LEM5, 45.5%; LEM10, 44.9%). At 12mo, a similar percentage of responders with a ≥20min CFB in sSOL was observed for LEM (LEM5, 40.4%; LEM10, 43.3%). A higher percentage of subjects with a CFB in sWASO of ≥60min was observed for LEM versus PBO at 6mo (PBO, 24.2%; LEM5, 27.8%: LEM10, 30.2%); similar percentages were observed at 12mo with LEM (LEM5, 27.8%; LEM10, 27.7%). The majority of treatment-emergent adverse events were mild/moderate.

Conclusion

LEM treatment provided important levels of sustained efficacy over the long term. LEM was well tolerated.

Support

Eisai Inc.
0481 Impact of Lemborexant on Fatigue Severity in Subjects with Clinically Significant Levels of Fatigue at Baseline
Authors: Rosenberg R , Kumar D , Pinner K , Perdomo C , Moline M
Published: May 2020

Introduction

In Phase 3 SUNRISE-1 (NCT02783729; E2006-G000-304) and SUNRISE-2 (NCT02952820; E2006-G000-303), lemborexant (LEM) provided significant benefit versus placebo on sleep diary-based sleep onset/maintenance outcomes over 1mo and 6mo, respectively, in subjects with insomnia disorder. The impact of LEM on patient-reported fatigue, assessed using the Fatigue Severity Scale (FSS), in subjects with clinically significant fatigue (CSF) at baseline was examined for each study.

Methods

SUNRISE-1 was a 1mo, randomized, double-blind, placebo- and active-controlled, parallel-group study in female (≥55y) and male (≥65y) subjects (n=1006); subjects received placebo, LEM 5mg (LEM5), LEM 10mg (LEM10) or zolpidem tartrate extended-release (not reported here). SUNRISE-2 was a 12mo, randomized, double-blind study in subjects age ≥18y (n=949). Subjects received placebo, LEM5, or LEM10 for 6mo. Placebo subjects were rerandomized to LEM5 or LEM10 for another 6mo; LEM subjects continued assigned treatment. CSF was defined as FSS total score (FSSts) ≥36.

Results

In subjects with baseline CSF, in SUNRISE-1, baseline FSSts was 46.8, 46.5, and 46.6 in placebo (n=117), LEM5 (n=157), and LEM10 (n=153) groups, respectively, and, in SUNRISE-2, was 45.7, 46.4, and 45.8 in placebo (n=169), LEM5 (n=181), and LEM10 (n=173) groups, respectively. At 1mo, mean changes from baseline in FSSts were not significantly different vs placebo for LEM5 in both studies, and for LEM10 in SUNRISE-1. In SUNRISE-2, LEM10 significantly decreased mean [SD] FSSts from baseline vs placebo at 1mo (LEM10, −11.2[13.9] vs placebo, −8.7[10.5]; P=0.03). By 6mo in SUNRISE-2, both LEM5 and LEM10 significantly decreased mean [SD] FSSts from baseline versus placebo (LEM5, −15.4[13.8]; LEM10, −15.0[14.2] vs placebo, −11.2[11.6]; both P<0.05). At 12mo, mean [SD] FSSts improvements were sustained for LEM5 (−20.4[12.8]) and LEM10 (−18.1[14.7]).

Conclusion

In subjects with CSF, longer treatments (>1mo) may be needed to observe significant FSSts improvements, which were evident at 6mo and sustained at 12mo with continuous LEM treatment.

Support

Eisai Inc.
0502 Safety, Tolerability, and Efficacy of a Novel, Highly Potent and Selective Partial Agonist for Nociceptin/Orphanin-FQ Peptide (NOP) Receptors in Patients with Insomnia Disorder
Authors: Zhou M , Harris S , Kapil R , Cipriano A , He E , Shet M , Fukumura K , Matsuo Y , Uehira M , Zammit G
Published: May 2020

Introduction

V117957 is a recently described investigational oral, potent, and selective nociceptin/orphanin-FQ peptide (NOP) receptor partial agonist which was previously evaluated in ~200 healthy subjects. Its satisfactory safety/tolerability profile has been established with the top doses at 30mg following a single oral administration and 10mg once daily for 2 weeks. V117957 demonstrated favorable drug-like properties for insomnia treatment, including oral bioavailability, fast absorption, and rapid elimination.

Methods

A total of 52 patients with insomnia disorder have been evaluated in two separate randomized, double-blind, crossover, placebo-controlled sleep studies. Insomnia disorder was confirmed by screening polysomnography (PSG). All subjects received orally, for two consecutive nights, either V117957 10mg or placebo in Study #1 or 0.5, 1, 3, 6mg or placebo in Study #2. Efficacy was measured via PSG for the primary endpoint of sleep efficiency (SE) and secondary endpoints of sleep onset (latency to persistent sleep [LPS]) and maintenance (wakefulness after sleep onset [WASO]). Efficacy also was measured by patient diary (subjective sleep latency [sSL], subjective total sleep time [sTST], sWASO). Pharmacodynamics (PD) on next-day residual effects were also measured, including cognitive, psychomotor and mood effects.

Results

V117957 showed statistically significant greater sleep efficiency and less WASO in a dose-dependent manner (0.5-10 mg) and a statistically significant reduction in LPS at 10mg, as compared to placebo. V117957 at 0.5mg and 1mg exhibited next-day residual effects similar to placebo. At doses of 3mg or higher, V117957 showed dose-dependent next-day residual effects. V117957 was safe and well-tolerated across all doses tested with no serious adverse events, with somnolence being the most frequent treatment-emergent adverse event. No concerning laboratory findings and no clinically significant findings on vital signs and electrocardiograms have been attributed to V117957 in these subjects.

Conclusion

V117957 was safe and well-tolerated in patients with insomnia disorder. These results demonstrated that NOP receptors represent a novel mechanistic treatment for insomnia disorder and support continued evaluation of V117957.

Support

Funded by Shionogi and Imbrium Therapeutics, a subsidiary of Purdue Pharma L.P.
0511 Patterns of Concomitant Over-the-Counter, Natural Product and Prescription Sleep Aid Use: A Population-Based Study
Authors: Cheung J M , Jarrin D C , Beaulieu-Bonneau S , Ivers H , Morin G , Morin C M
Published: May 2020

Introduction

Despite limited evidence, over-the-counter medications (OTC) and natural products (NP) are increasingly combined with prescribed medications (Rx) to manage insomnia symptoms. Self-medication patterns are expected to be heterogenous and may predispose individuals to inappropriate medication-taking behaviors, but little is known about the usage trajectories of sleep aids. This study investigates patterns of concomitant NP, OTC and Rx use in a Canadian population-based sample.

Methods

Data were derived from a longitudinal study on the natural history of insomnia. Participants were 3416 adults (62% female, Mage = 49.7, MInsomnia Severity Index= 8.4). Self-reported data for OTC, NP and Rx use in the last year (yes/no) was extracted at 0-, 6- and 12-month follow-up. A Latent Class Growth Curve Analysis was conducted to identify patterns of concomitant sleep aid use. Participants also completed a battery of clinical measures including the Ford Insomnia Response to Stress Test, Dysfunctional Beliefs and Attitudes about Sleep scale (16-item), Beck Depression Inventory, Insomnia Severity Index and the Pittsburgh Sleep Quality Index. Preliminary associations between class membership and baseline covariates were evaluated using the χ 2 test or a one-way ANOVA. Sampling weights were applied to all analyses, adjusting for partial non-response.

Results

Analyses revealed a 6-class solution; each class reflected a preferential agent(s) choice, which remained stable over 12-months: Minimal Use (74.5%), Rx-Dominant (11.3%), NP-Dominant (6.3%), OTC-Dominant (4.3%), Rx-NP-Dominant (2.4%), and Rx-OTC-Dominant (1.1%). Classes with prominent prescribed agent use were older [F(5, 207.6) =27.2, p<0.001], more likely to seek help [χ 2(5, n=2977) =653.1, p< 0.001] and consume alcohol [χ 2(5, n=2968) =49.2, p< 0.001]. Clinically, these individuals reported greater stress reactivity [F(5, 2966) =48.4, p< 0.001], depressive symptoms [F(5,197.4) =32.0, p<0.001], dysfunctional sleep beliefs [F(5, 2987) =54.3, p< 0.001], insomnia severity [F(5, 2983) =88.4, p< 0.001] and poorer sleep quality [F(5, 203.8) =124.2, p< 0.001].

Conclusion

A majority of adults used agents minimally. Stability of medication-taking patterns suggests that individuals adopt less sporadic approaches when combining sleep aids than previously assumed. Clinical profiles and sleep aid choice could pre-empt vulnerabilities to inappropriate self-medication.

Support

Research supported by a grant from the Canadian Institutes of Health Research (MOP#115103)
0512 Impact of a Patient Decision-Aid When Selecting Insomnia Treatments and Factors Associated with Decisional Conflict: Preliminary Findings from an Ongoing Pragmatic Clinical Trial
Authors: Cheung J M , Ji X , Ivers H , Morin C M
Published: May 2020

Introduction

Preferences play an important role in determining insomnia treatment outcomes, but the validity of patient choice is rarely assessed. Uninformed preferences can lead to decisional conflict, which can negatively impact on treatment initiation, adherence, and subsequent outcomes. The current study aims to evaluate the impact of integrating a patient decision-aid as part of a pragmatic clinical trial and to identify baseline covariates associated with clinically significant decisional conflict (CSDC).

Methods

Secondary analysis of an ongoing pragmatic clinical trial for a two-stage cognitive behavioral therapy for insomnia (CBT-I) intervention was undertaken. Participants were referred from primary care clinics in Quebec City, Canada. Upon enrolment, participants were guided by a decision-aid, outlining the risks and benefits of prospective treatment options, when selecting their preferred arm of treatment in Phase 1. Options included SHUTi, SHUTi combined with an existing medication or continuing usual treatment with medication alone. Participants also completed a battery of sleep and mental health measures at baseline. Prior to treatment initiation, the 4-item SURE (Sure of myself; Understand information; Risk-Benefit ratio; Encouragement) scale was administered to screen for CSDC. Relationships between CSDC and baseline covariates were explored using Pearson correlations.

Results

Of the 55 participants initially enrolled, 94.5% (n=52) of participants preferentially selected SHUTi, either as sole treatment (n=24) or in combination with an existing medication (n=28), over usual treatment with medication alone (n=3). Overall, CSDC was only reported by 5.5% (n=3) of the sample population, with no group differences observed, suggesting effective clarification of treatment options through the decision-aid. Interestingly, higher SURE scores (i.e. less decisional conflict) were negatively correlated with depressive symptoms (r= -0.295, n= 55, p= 0.029) and anxiety symptoms (r= -0.301, n= 55, p= 0.026). Correlations with age, insomnia symptoms, duration of insomnia and fatigue were not statistically significant.

Conclusion

The patient decision-aid appeared to resolve decisional conflict for 94.5% (n=52) of participants. Findings allude to the potential influence of emotional status on information processing pathways in an insomnia context, warranting further research.

Support

Research supported by a grant from the Canadian Institutes of Health Research (CIHR-IRSC:0441002152).