bluuebunny/crossref_metadata_2025_split huggingface dataset:
0354 Effect of Lemborexant on Sleep Architecture in Subjects with Comorbid Insomnia and Mild Obstructive Sleep Apnea from a Ph 3 Trial
Authors: Kushida Clete , Zammit Gary , Cheng Jocelyn , Kumar Dinesh , Moline Margaret 
Published: May 2023

Abstract

Introduction
Many patients with insomnia have co-morbid obstructive sleep apnea (COMISA). Patients with obstructive sleep apnea (OSA) may also have decreased REM-sleep. Lemborexant (LEM) is a dual-orexin-receptor-antagonist approved to treat adults with insomnia. LEM has been demonstrated to increase total sleep, with prominent increases in rapid eye movement (REM). Thus, sleep architecture was analyzed in subjects with insomnia/mild OSA receiving LEM in a phase 3 trial.

Methods
Study 304 (E2006-G000-304; NCT02783729) was a 1-month, randomized, double-blind, placebo (PBO)-controlled and active-comparator study in adults ≥55y with insomnia disorder. Subjects received PBO, LEM 5mg (LEM5), LEM 10mg (LEM10) or zolpidem tartrate extended-release 6.25mg (ZOL). Least-squares-mean (LSM) duration of each sleep stage (minutes) was compared across treatment groups from pooled data on Nights (NT)1/2 and NT29/30 for ­subjects with mild OSA (apnea hypopnea index ≥5 to &lt; 15). Treatment-emergent adverse events (TEAEs) were recorded.

Results
The analysis set comprised 409 subjects (LEM5=114/LEM10=105/ZOL=112/PBO=78) with mild OSA. Mean (SD) change from baseline (CFB) in total sleep time was significantly larger (more sleep) in both LEM groups than ZOL or PBO at the post-randomization assessments. CFB for REM sleep was also significantly larger (P&lt; 0.0001) for both LEM vs ZOL/PBO at both assessments, NT1/2: LEM5 21.08 (21.79), LEM10 32.57 (24.34), ZOL 3.06 (23.51), PBO 2.42 (17.51); NT29/20: LEM5 14.49 (18.12), LEM10 24.26 (24.50), ZOL 0.75 (22.32), PBO 2.14 (22.62). Compared with PBO, CFB for total nonREM sleep significantly increased (P&lt; 0.0001) in the LEM groups at both assessments, NT1/2: LEM5 39.64 (34.30), LEM10 44.63 (37.85), ZOL 45.80 (37.43); PBO 7.80 (37.88); NT29/30: LEM5 44.66 (37.77), LEM10 44.08 (39.68), ZOL 36.22 (41.95), PBO 15.33 (36.52). Compared to ZOL, total nonREM sleep in either LEM group was not significantly different on NT1/2, and only LEM5 was significantly different vs ZOL at NT29/30 (P&lt; 0.05). LEM was well-tolerated; most TEAEs were mild/moderate.

Conclusion
LEM significantly increased total sleep time in subjects with insomnia and mild OSA. The additional sleep was comprised importantly with REM sleep, a sleep stage that may be decreased in patients with OSA. These data support the use of LEM in a population with COMISA.

Support (if any)
Eisai Inc.
0356 Is There an Association Between Insomnia and Temperament in Adults?
Authors: Lundy Bethany , Noall Carissa , Kay Daniel 
Published: May 2023

Abstract

Introduction
Insomnia is an increasingly prevalent health concern influenced by environmental, biological, and dispositional factors. Adult temperament is the collection of fundamental characteristics that some have hypothesized may predispose individuals to insomnia. Despite this, there is little research on the relationship between insomnia and specific temperament factors in adults. A few investigations have shown negative affect as the most consistent association with poor sleep. This study investigated relationships between insomnia and adult temperament and tested whether the association between negative affect and insomnia is better explained by depression.

Methods
Participants were 66 adults, (Mdn = 23, 18-49 years old), 50% female, 86% white, ranging from good (no insomnia) to poor sleepers (mild to moderate insomnia). Data were pooled from two protocols designed to investigate associations between sleep and transdiagnostic features of mental illness. As part of a broader array of questionnaires and assessments, participants completed the insomnia severity index (ISI), adult temperament questionnaire (ATQ), and the patient health questionnaire-9 (PHQ-9). The ATQ subscales were calculated according to previously identified factors: negative affect, effortful control, orienting sensitivity, and extraversion/surgency. Spearman’s coefficient was used to explore associations between each temperament factor and insomnia severity. Multiple regression was used to determine whether the associations between insomnia severity and negative affect remained when adjusting for PHQ-9 total score, not including the sleep items.

Results
Insomnia severity was significantly correlated with negative affect (ρ = 0.345, p = .005), but no other temperament factors (p&gt; .05, for all). Regression analysis of all four ATQ factors and the PHQ-9 in predicting ISI outcomes resulted in an R2 of .45, PHQ-9 being the only significant regressor (p&lt; .05).

Conclusion
We failed to find support for the hypothesis that individual differences in temperament confer risk for insomnia. Although insomnia was associated with negative affect in bivariate correlation analysis, this association may be better explained by their shared association with depression. We recommend investigating how temperament interacts with various psychological conditions such as depression and anxiety to better understand the individual differences that may impact risks for developing insomnia.

Support (if any)
n/a
0358 Prevalence of Insomnia Symptoms and Insomnia Disorder within VA Subacute Rehabilitation
Authors: Boeve Angelica , Boyle Julia , Moye Jennifer , Driver Jane , Ruopp Marcus , O'Malley Kelly 
Published: May 2023

Abstract

Introduction
Approximately 40% of Veterans report insomnia symptoms and 12% of Veterans have a formal insomnia disorder diagnosis. While these numbers reflect outpatient prevalence rates, there is little data on the prevalence of insomnia symptoms and insomnia disorder among the 32,000 Veterans receiving care within VA Community Living Centers (CLC) (rehabilitation and long-term care facilities) each year. The present analysis provides an initial step in understanding the prevalence of insomnia disorder vs. insomnia symptoms within a local VA CLC subacute rehabilitation unit. This analysis is part of a clinical innovation project that evaluated Veterans’ sleep during admission for the purposes of informing clinical interventions.

Methods
67 Veterans were admitted to a VA subacute rehabilitation unit following hospital discharge between March and August 2022. Veterans were asked to complete a brief evaluation within 7 days of admission, including the Insomnia Severity Index (ISI), Sleep Need Questionnaire (SNQ), and Epworth Sleepiness Scale (ESS). Sleep disorder diagnoses were obtained through chart reviews. Descriptive statistics were used to evaluate the prevalence of sleep disorders, insomnia severity, sleep need, and daytime sleepiness.

Results
48 of 67 (71.6%) Veterans (Mage=72.8±12.0;97.9%male;79.2%white) completed evaluations within 7 days of admission. 52.1% of Veterans reported at least subthreshold insomnia (ISI≥8) with 22.9% reporting moderately severe clinical insomnia (ISI≥15). 50% reported not meeting their sleep need (SNQ≥13) and 33.3% reported at least mild levels of daytime sleepiness (ESS≥11). Chart reviews indicated only 25% of Veterans had a formal sleep disorder diagnosis in their chart and only 4.2% Veterans had a formal diagnosis of insomnia disorder.

Conclusion
The results of this preliminary analysis highlighted the discrepancy between national outpatient statistics and local inpatient statistics on the prevalence of insomnia symptoms and disorder. While the Veterans admitted to the CLC may be experiencing additional factors influencing their sleep (e.g., environmental disruptors), this does not wholly explain the discrepancy between the local and national ­samples. Future evaluations should include multiple VA sites to obtain a more representative sample of Veterans. Clinically, these findings suggest that insomnia disorder should be considered a standalone diagnosis and added to Veterans’ charts when clinically elevated symptomology is endorsed.

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0359 Relationships Between Sleep Valuation and Sleep Patterns
Authors: Lundy Bethany , Nielson Spencer , Kay Daniel 
Published: May 2023

Abstract

Introduction
Sleep valuation is the relative worth placed on sleep. Individual differences in sleep valuation relate to age, gender, depression, and overall sleep health. The factor structure of sleep valuation and how subfactors of sleep valuation relate to sleep health outcomes remain unclear. This study investigated how latent factors of sleep valuation relate to sleep health.

Methods
Data were collected from 125 adults, primarily college students (59% female, mean age 21, and 87% white), who completed the 43-item Sleep Valuation Item Bank, the Insomnia Severity Index, and a standard sleep diary. Based on observations from a previous study, sleep valuation items were separated from sleep devaluation items and principal axis factoring analyses were run for each set of items. Spearman’s correlation analyses were used to explore associations between sleep valuation and devaluation subfactors with demographics, general and mental health, insomnia severity, in bed time, total sleep time, and sleep efficiency reported on the sleep diary for the prior night.

Results
Based on the scree plot method, three sleep valuation (sleep wanting, preference/prioritizing, and enjoyment) and two devaluation (sleep aversion and procrastination) subfactors emerged in the factor analysis. Greater sleep wanting was associated with female gender, poorer general and mental health, more severe insomnia, and later bedtime, p&lt;.05, for all. Sleep preference/prioritizing was associated with female gender and poorer mental health, p&lt;.05, for all. Sleep enjoyment was associated with lower insomnia severity and greater sleep efficiency, p&lt;.05, for all. Sleep aversion was not associated with any sleep diary variable. Sleep procrastination was associated with a later bedtime, less time in bed, and greater insomnia severity, p&lt;.05, for all.

Conclusion
Findings closely replicated prior studies including a similar factor structure and the association of sleep valuation to gender, mental and physical health, and insomnia severity. Sleep valuation and devaluation patterns were intimately related to self-reported sleep behaviors. The direction of these associations could not be determined. Nevertheless, we recommend development and testing of primary and tertiary interventions that target sleep valuation patterns to explore their impact on sleep health behaviors.

Support (if any)
n/a
0360 Shifts in Daytime Functioning Items on the Insomnia Severity Scale with Lemborexant after 6 Months of Treatment
Authors: Chepke Craig , Cote Kimberly , Pinner Kate , Yardley Jane , Moline Margaret 
Published: May 2023

Abstract

Introduction
The Insomnia Severity Index (ISI) is a 7-item self-reported questionnaire evaluating perception of symptom severity included in Phase 3 studies of lemborexant (LEM), a competitive dual orexin receptor antagonist approved in several countries to treat adults with insomnia. The ISI total score, and items 4-7 for daytime function (DF), improved significantly with LEM treatment compared to placebo (PBO) as assessed at 1, 3 and 6 months. Here we report shifts in DF scores at 6 months depending on baseline severity.

Methods
Study 303 was a 12-month, randomized, double-blind PBO-controlled (first 6months; Treatment Period 1 [TP1]) phase 3 study in subjects (age ≥18y) with insomnia disorder. Subjects were randomized to PBO, LEM 5mg (LEM5) or 10mg (LEM10) for 6 months. ISI items are rated on a 5-point Likert scale from 0 (no problem) to 4 (very severe problem). Daytime-related items include ratings on sleep satisfaction, extent symptoms are noticeable to others, cause worry/distress, or interferes with daily function. Data were analyzed by Cochran-Mantel-Haenszel test of general association vs placebo.

Results
Of the 949 subjects, 749 (78.9%) completed the ISI at baseline and end of TP1: PBO (258/318 [81.1%]; LEM5, 257/316 [81.3%]; LEM10, 234/315 [74.3%]). Baseline daytime ISI-total-score distribution was similar between groups; most had scores of 9-12 (66.7-68.6%). At the end of TP1, more subjects with baseline scores of 9-12 shifted to 0-4 with LEM5 (49.7%) and LEM10 (46.2%) than with PBO (26.6%). Similarly, more subjects with baseline scores of 13-16 shifted to 0-4 with LEM5 (39.1%) and LEM10 (46.3%) than with PBO (29.6%). An additional 28.1% and 25.9% of subjects with LEM5 or LEM10, respectively, with baseline scores of 13-16 shifted to scores of 9-12, compared with 31.5% of PBO. The overall shift distributions were significantly different, favoring both LEM groups (p&lt; 0.01).

Conclusion
More LEM-treated subjects improved in daytime functioning as evidenced by the significantly large number of subjects whose scores moved into the lower categories (i.e., better sleep) compared with PBO subjects. These data support important improvements in daytime function that are evident even after 6 months of continuous LEM treatment.

Support (if any)
Eisai Inc.
0364 The Effect of Lemborexant on Polysomnographic Sleep Parameters in Adults with Mild, Moderate, or Severe Obstructive Sleep Apnea
Authors: Moline Margaret , Cheng Jocelyn , Hall Nancy , Shah Dhara , Zammit Gary 
Published: May 2023

Abstract

Introduction
Several commonly prescribed hypnotics may worsen respiratory function, especially in the elderly. Lemborexant (LEM) is a dual-orexin-receptor-antagonist approved to treat adults with insomnia. In Studies 102 (NCT03471871) and 113 (NCT04647383), LEM demonstrated respiratory safety in subjects with mild, moderate, or severe obstructive sleep apnea (OSA) who did not report insomnia. The current analyses evaluated sleep variables from these studies.

Methods
Studies 102 and 113 were double-blind, placebo (PBO)-controlled, crossover studies in adults with untreated mild (apnea-hypopnea-index [AHI] ≥5 to &lt; 15), moderate (AHI≥15 to &lt; 30), or severe (AHI≥30) OSA, without insomnia. Subjects were randomized to two 8-night periods (separated by ≥14 days) treated with LEM 10mg (LEM10) or PBO. Latency to persistent sleep (LPS), sleep efficiency (SE), and wake after sleep onset (WASO) were assessed using polysomnography on Days 1 (D1) and 8 (D8).

Results
The analysis set comprised 39, 13, and 20 subjects with mild, moderate, or severe OSA, respectively. On both days, LPS was not statistically different from PBO in any group. Compared with PBO, SE was significantly greater on D1 in subjects with mild (LEM10, 90.43; PBO, 80.31; P&lt; 0.0001), moderate (LEM10, 88.83; PBO, 84.02; P=0.016), and severe (LEM10, 87.76; PBO, 77.84; P&lt; 0.0001) OSA. On D8, SE was significantly greater in subjects with mild (LEM10, 86.65; PBO, 80.59; P=0.003) and moderate (LEM10, 88.45; PBO, 80.70; P=0.004) OSA, with a trend towards significance in subjects with severe (LEM10, 85.60; PBO, 80.63; P=0.055) OSA. WASO was significantly lower (improved) on D1 in subjects with mild (LEM10, 33.30; PBO, 76.76; P&lt; 0.0001), moderate (LEM10, 44.26; PBO, 64.71; P=0.008), and severe (LEM10, 42.03; PBO, 91.49; P&lt; 0.0001) OSA. On D8, WASO was significantly lower in subjects with mild (LEM10, 51.74; PBO, 70.52; P=0.015) and moderate (LEM10, 49.16; PBO, 75.15; P=0.008) but not severe (LEM10, 59.85; PBO, 74.46; P=0.161) OSA. LEM was well-tolerated.

Conclusion
In untreated OSA subjects without insomnia, irrespective of OSA severity, LEM improved sleep maintenance versus PBO. LPS did not differ between treatments since such patients may not report sleep onset difficulties. These findings support the use of LEM for patients with comorbid insomnia and sleep apnea (COMISA).

Support (if any)
Eisai, Inc.
0367 Urban Stress and Sleep Health by Proximal Neighborhood Groups in Washington, DC
Authors: Jackson Alexus , Ize-Iyamu Osayi , DeLeon Rodrigo , Poindexter Milan , Mellman Thomas 
Published: May 2023

Abstract

Introduction
African Americans are disproportionately affected by environmental factors that increase the risk for negative health outcomes. Analyses from National Health Interview Survey (NHIS) data estimated 15 to 75 percent of the disparities between Black and White respondents being accounted for by residential context. Poor sleep health, particularly short sleep duration, has been linked to metabolic and cardiovascular disease. A population study indicated that sleep duration of less than 6 hours was more common among African Americans compared with other racial groups in the United States and this association was accounted for by African Americans living in high density urban environments. Threats of violence may engender feelings of vulnerability when sleeping and be an important determinant of sleep health though this relationship has not been adequately studied. The aim of this study is to determine how an individual’s sleep health relates to violent crime rates in their neighborhood of residence as well as indicators of neighborhood stress endorsed in a self-reported survey.

Methods
African- American men and women between the ages of 18-35 filled out the insomnia severity index (ISI) and city stress inventory (CSI). Sleep duration and sleep efficiency were obtained through home-based actigraphy. Participants were categorized as poor sleepers if two out of three criteria were met: sleep duration of less than six hours, ISI greater than 10, and sleep efficiency below 85%. Participants addresses were linked to one of the 51 proximal neighborhood groups (PNG) defined by the DC Department of Health and Office of Planning using MAR geocoder and QGIS mapping software. Violent death rates and other social health determinants are indicated by PNG in the DC DOH’s Health Equity Report (2019).

Results
Sleep measures were not correlated with neighborhood violent death rates (Pearson r’s: .05 - .17; all NS). SE and TST were weakly correlated with CSI scores (both r’s = -.22, NS).

Conclusion
The negative findings may be related to sample size, the presence of threat and crime in all of the locations, and the importance of individual coping.

Support (if any)
NIHLB grant R01HL136626 to Dr. Thomas A. Mellman and NCATS grant for a Clinical Translational Science Award UL1-TR001409.
0370 A three-arm randomized controlled trial examining mindfulness-based and cognitive-behavioral therapies for prenatal insomnia
Authors: Kalmbach David , Cheng Philip , Ong Jason , Reffi Anthony , Fellman-Couture Cynthia , Seymour Grace , Bayoneto Alec , Roth Thomas , Drake Christopher 
Published: May 2023

Abstract

Introduction
Cognitive behavioral therapy for insomnia (CBTI) improves sleep in pregnancy, but its therapeutic benefits may be diminished in pregnancy due to undertreatment of cognitive arousal (i.e., heightened cognitive activity, especially at night). A recent proof-of-concept, single-arm trial suggested that combining behavioral sleep strategies with mindfulness components produced large reductions in prenatal insomnia, depression, and cognitive arousal. The present study was a randomized controlled trial evaluating the effectiveness of this mindfulness-based intervention and CBTI relative to a control condition.

Methods
Sixty-four pregnant women with clinically significant insomnia symptoms were randomized to a mindfulness-based intervention, CBTI, or control. The mindfulness intervention was Perinatal Understanding of Mindful Awareness for Sleep (PUMAS), which places behavioral sleep strategies within a mindfulness framework and tailors all components to pregnancy. PUMAS and CBTI were delivered via six telemedicine sessions, whereas control patients electronically received six weekly information sheets on perinatal sleep health. Treatment outcomes were assessed before and after treatment, which included the insomnia severity index (ISI), Edinburgh postnatal depression scale (EPDS), and pre-sleep arousal scale’s cognitive factor (PSASC; nocturnal cognitive arousal). Treatment outcomes were analyzed via general linear models, and the PRODCLIN method tested mediation models in evaluation of treatment mechanisms.

Results
Intent-to-treat analyses revealed significant ISI reductions in the PUMAS (-11.05±3.84) and CBTI (-11.20±6.87) conditions relative to control (-4.27±1.96). Insomnia remission rates were highest among PUMAS patients (81.8%), whereas 65.0% of CBTI patients and 13.6% of controls remitted. PUMAS significantly alleviated depression relative to control (EPDS: -3.77±3.88 vs -0.59±2.84, p=.017), whereas CBTI did not differ from either group (EPDS: -2.55±4.25, p-values ≥ .271). Similarly, PUMAS alleviated cognitive arousal relative to control (PSASC: -8.82±4.99 vs -3.45±4.53, p=.009), whereas CBTI did not differ from either group (PSASC: -7.30±7.49, p-values ≥ .104). Mediation analyses estimated that reductions in cognitive arousal mediated 26.6% and 40.6% of PUMAS effects on insomnia and depression.

Conclusion
PUMAS alleviated insomnia, depression, and cognitive arousal relative to control. Reducing cognitive arousal was a significant treatment mechanism by which PUMAS alleviated insomnia and depression. By comparison, CBTI significantly alleviated insomnia relative to control, but yielded no significant effects on depression or cognitive arousal.

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0371 Acute effects of cannabinoids in insomnia disorder: a randomised, placebo-controlled trial using high-density EEG
Authors: Suraev Anastasia , McGregor Iain , Marshall Nathaniel , Kao Tancy , D'Rozario Angela , Grunstein Ron , Hoyos Camilla 
Published: May 2023

Abstract

Introduction
Medicinal cannabis is often cited as a popular alternative to common sleep aids; however, there are limited studies using complex sleep EEG methods examining its’ effects in insomnia disorder.

Methods
Twenty participants (16 female; mean [SD] age, 47.1 [8.7] years) with insomnia disorder (mean ISI=20.8) completed two 24-hour in-laboratory visits during which they received a single oral dose of ‘CBD/THC’ containing 200 mg cannabidiol (CBD) and 10 mg Δ9-tetrahydrocannabinol (THC) or matched placebo. Co-primary outcomes were total sleep time (TST) and wake after sleep onset (WASO). Secondary outcomes included next-day neurobehavioural function and sleep architecture metrics determined using overnight polysomnography with high-density EEG. Trial registration: ACTRN12619000714189.

Results
Compared to placebo, CBD/THC significantly decreased TST (-24.5 min, p=0.047) with no significant change to WASO (+10.7 min, p=0.422). CBD/THC significantly decreased time spent in REM sleep (-8.1%, p&lt; 0.001) and increased REM sleep latency (+65.6 min, p=0.008). High-density EEG analysis revealed a significant reduction in high-frequency EEG activity overlying the posterior and frontal cortex during N2 sleep with CBD/THC treatment compared to placebo. CBD/THC treatment also reduced delta activity in the posterior region of the brain during N3 sleep and increased alpha and beta activity during REM sleep in the posterior regions of the brain relative to placebo (all p’s&lt; 0.05). CBD/THC did not impair next-day (+12 h post-treatment) cognitive performance, alertness, or simulated driving performance (all p’s&gt;0.05). Eighty-five mild, non-serious, adverse events were reported (55 during ETC120; most common dry mouth, drowsiness, and fatigue).

Conclusion
An acute dose of combined 200 mg CBD and 10 mg THC reduced TST with a clear effect of REM sleep suppression. However, no next-day residual impairment on cognitive function, alertness or simulated driving performance were observed. Further research is required to determine the impact of chronic cannabinoid dosing on REM sleep and other objective sleep outcomes in insomnia disorder.

Support (if any)
The study was funded by the Lambert Initiative for Cannabinoid Therapeutics, a philanthropically funded centre for cannabinoid research at the University of Sydney, Australia.