bluuebunny/crossref_metadata_2025_split huggingface dataset:
335 Evaluation of Dose Transition From Zolpidem to Lemborexant Across 14 Weeks: Results From a Multicenter Open-label Pilot Study
Authors: Rosenberg Russell , Amchin Jess , Kumar Dinesh , Perdomo Carlos , Atkins Norman , Moline Margaret , Malhotra Manoj 
Published: May 2021

Abstract

Introduction
E2006-A001-312 (Study 312; NCT04009577) was an open-label pilot study that examined pre-specified dosing paradigms for transitioning patients from zolpidem (ZOL: immediate [IR] or extended-release [ER]) to the dual orexin receptor antagonist lemborexant (LEM; 5mg [LEM5] or 10mg [LEM10]).

Methods
Study 312 included a 3-week Screening Period (subjects continued ZOL), 2-week Titration Period (TITR), 12-week Extension Period (EXT), and 4-week Follow-up Period. Adults with insomnia who were intermittent (3–4 nights/week) or frequent (≥5 nights/week) ZOL-IR or ZOL-ER users participated. Intermittent ZOL users and subjects with one week each of intermittent and frequent ZOL usage were assigned to Cohort-1 and began TITR with LEM5. Frequent ZOL users were assigned to Cohort-2 and randomized 1:1 to LEM5 or LEM10. Subjects who successfully transitioned to LEM had the option to enter EXT. During TITR and EXT, subjects could change LEM dose (only once during TITR). The primary endpoint was the proportion of subjects who transitioned to LEM at the end of TITR. Treatment-emergent adverse events (TEAEs) were assessed based on dose at time of TEAE.

Results
Fifty-three subjects enrolled (Cohort-1, n=10; Cohort-2, n=43). Of these, 43/53 (81.1%) transitioned to LEM at the end of TITR; all 43 (100.0%) entered EXT wherein 41/43 subjects received treatment. Three of these subjects discontinued treatment during EXT, so that 38/41 (92.7%) subjects entered EXT, received treatment and completed EXT. At the end of EXT, 25/41 (61.0%) subjects were receiving LEM10 and 16/41 (39.0%) were receiving LEM5. Based on modal dose (most frequent dose taken during TITR and EXT combined) groups, median time to first dose change was 14.5 days and 36.0 days for LEM5 and LEM10, respectively. The majority of TEAEs were mild/moderate in severity. Across the study (TITR and EXT), more TEAEs occurred with LEM10 than LEM5; the most common TEAEs were somnolence (n=4) and abnormal dreams (n=4).

Conclusion
Study results support the view that patients can successfully transition directly from ZOL to LEM. LEM was generally well tolerated; the safety profile was consistent with that observed in Phase 3 clinical development.

Support (if any)
Eisai Inc.
339 Long-term Perception of Medication Effectiveness in Subjects Receiving Lemborexant for up to 12 Months
Authors: Drake Christopher , Yardley Jane , Pinner Kate , Perdomo Carlos , Moline Margaret 
Published: May 2021

Abstract

Introduction
The Patient Global Impression–Insomnia version (PGI-I) is a self-report instrument used to evaluate a patient’s perception of the effects of their insomnia medication on their sleep relative to starting treatment. The PGI-I includes 3 items related to medication effects (helped/worsened sleep; decreased/increased time to fall asleep; and increased/decreased total sleep; responses include: 1=positive, 2=neutral, 3=negative) and 1 item related to perceived appropriateness of study medication strength (responses include: 1=too strong, 2=just right, 3=too weak). In Study E2006-G000-303 (Study 303; SUNRISE-2; NCT02952820), significantly greater percentages of subjects reported a positive impact of the dual orexin receptor antagonist lemborexant (LEM) versus placebo (PBO) at 1, 3, and 6mo for each of the PGI-I items related to medication effects. PGI-I results at 9 and 12mo are presented here for subjects that received continuous treatment with LEM for up to 12mo.

Methods
Study 303 was a 12-mo, randomized, double-blind, PBO-controlled (first 6mo [Period 1]), phase 3 study. Subjects were aged ≥18y with insomnia disorder. During Period 1, subjects received PBO (n=318) or LEM (5mg, [LEM5], n=316; 10mg, [LEM10], n=315). During Period 2 (second 6mo), LEM subjects continued their assigned dose while PBO subjects were rerandomized to LEM5 or LEM10 (reported separately). Subjects were also administered the PGI-I at months 9 and 12.

Results
At 9 and 12mo, the majority of LEM5 (9mo, n=241; 12mo, n=205) and LEM10 (9mo, n=211; 12mo, n=192) subjects reported that their study medication “helped” sleep at night (9mo: LEM5=73.4%; LEM10=76.3%; 12mo: LEM5=74.6%; LEM10=77.6%), reduced time to fall asleep (9mo: LEM5=79.3%, LEM10=78.2%; 12mo: LEM5=76.6%, LEM10=80.2%), and increased total sleep time (9mo: LEM5=62.2%, LEM10=73.0%; 12mo: LEM5=62.4%; LEM10=65.1%). Also, at both 9 and 12mo, the majority of subjects in the LEM5 and LEM10 groups, responded that treatment strength was “just right” (9mo: LEM5=60.6%, LEM10=62.1%; 12mo: LEM5=63.4%; LEM10=60.4%). LEM was well tolerated. Most adverse events were mild or moderate.

Conclusion
The majority of subjects receiving LEM5 or LEM10 reported a positive medication effect at both 9 and 12mo, sustaining similar positive effects for LEM achieved earlier, during the first 6mo of treatment in Study 303.

Support (if any)
Eisai Inc.
351 Informal Caregivers with Insomnia May Benefit From an Insomnia Treatment Using an Acceptance and Commitment Therapy Approach
Authors: Song Yeonsu , McGowan Sarah Kate , Kelly Monica , Carlson Gwendolyn , Fung Constance , Josephson Karen , Zeidler Michelle , Alessi Cathy , Martin Jennifer 
Published: May 2021

Abstract

Introduction
Insomnia among informal caregivers (providing care to family/friends) is common and associated with worse mental and physical health outcomes. Traditional cognitive behavioral therapy for insomnia may be challenging for caregivers whose beliefs about sleep may relate to beliefs and behaviors that are intertwined with their unique situation of caregiving. We examined whether an insomnia treatment using an acceptance and commitment (ACT) approach (i.e. committing to values-based actions toward goals vs. experiential avoidance of distressing emotions/thoughts) plus sleep restriction, stimulus control and sleep hygiene improves sleep, mental health, and daytime symptoms among caregivers.

Methods
We analyzed data from women veterans with insomnia who were informal caregivers (mean age=44 years [range 25–57]; N=6) and were participating in a clinical trial of an ACT-focused treatment (termed ABC-I). We measured: Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Patient Health Questionnaire (PHQ-9), General Anxiety Disorder (GAD-7), 11 items assessing symptoms of daytime impairment due to poor sleep derived from the International Classification of Sleep Disorders-Third Edition, and the Acceptance and Action Questionnaire (AAQ). Student t-tests were used to compare outcomes between pre- and post-ABC-I.

Results
Caregivers showed significant improvements between pre- and post-ABC-I (all p-values&lt;0.05) in the following outcomes: ISI (14.3±5.4 vs. 3.8±3.2), PHQ-9 (9.8±7.2 vs. 2.8±3.8), GAD-9 (9.0±6.6 vs. 2.0±1.8), and number of symptoms of sleep-related daytime impairment (6.8±4.0 vs. 3.8±3.5). Caregivers also showed improvement trends in PSQI (10.0±4.1 vs. 5.2±1.2, p=0.06) and AAQ score (24.0±12.7 vs. 16.2±8.0, p=0.05).

Conclusion
We found that caregivers with insomnia may benefit from ACT-based treatment in improving perceived sleep quality and insomnia, depression, anxiety, sleep-related daytime impairment and reduced experiential avoidance. This approach may increase motivation by linking the sleep program to core values, and acceptance and tolerance of emotions or thoughts may benefit caregivers with insomnia. Further studies using an ACT-based insomnia program are needed to test its effect in a larger sample of caregivers and evaluate benefits in terms of reduced stress and improved health.

Support (if any)
VA HSR&D (Martin IIR 13-058-2 and RCS-20–191), NIA (K23AG055668, Song), NHLBI (K23HL143055, Martin) of the NIH, VAGLAHS GRECC, and VA Office of Academic Affiliations (Kelly; Carlson).
352 Feasibility of Hypnosis as Adjunctive Treatment for Subjective Sleep Disturbance: A Pilot Study and Proof of Concept
Authors: Zhao Emma , Faerman Afik , Spiegel David 
Published: May 2021

Abstract

Introduction
Hypnosis-based interventions have been shown to have a positive impact on several dimensions of sleep health. However, current evidence is limited as only a paucity of studies included populations with sleep complaints. Here we present a pilot data set to demonstrate the feasibility of developing a hypnosis-based adjunctive treatment for subjective sleep complaints.

Methods
Eleven adults (42% female; mean age 45±16.87 years) who sought treatment at the Stanford Sleep Medicine Center or Center for Integrative Medicine for subjective sleep complaints received hypnosis as adjunctive treatment. Self-report questionnaires were used to assess the weekly frequency of subjective sleep disturbances experienced before and after treatment, as well as 5-point Likert scale ratings of perceived qualitative improvement in symptom severity and overall sleep quality.

Results
Five participants (45%) reported a reduction in symptom frequency and severity after hypnosis treatment. All five participants attributed at least some of the improvement to hypnosis treatment. Most participants (63%) observed post-treatment improvements in their overall sleep quality. No participants reported adverse effects of hypnosis.

Conclusion
Results suggest hypnosis-based adjunctive treatment may be effective for alleviating subjective sleep disturbances. The findings serve as preliminary support for further randomly controlled trials in larger samples.
Support (if any):
359 Tailoring of Cognitive Behavior Therapy for Insomnia for Patients with Kidney Failure Undergoing Hemodialysis: The SLEEP-HD Study
Authors: McCurry Susan , Cukor Daniel , Clark Carlyn , Brady Nisha , Rue Tessa , Unruh Mark , Mehrotra Rajnish 
Published: May 2021

Abstract

Introduction
Patients with kidney failure treated with hemodialysis (HD) frequently report insomnia symptoms. Cognitive-behavior therapy for insomnia (CBT-I) is a first line treatment for insomnia but there are unique issues surrounding kidney failure and HD that impact patients’ ability to access CBT-I and follow standard treatment recommendations. This presentation describes CBT-I protocol modifications made to address these issues as part of an ongoing multi-center clinical trial testing the efficacy of telehealth CBT-I compared to trazodone or medication placebo control.

Methods
CBT-I protocol modifications were made prior to starting the SLEEP-HD randomized trial based upon unique clinical considerations for HD patients, e.g., irregular sleep-wake scheduling that HD treatment demands, and napping during HD sessions or afterwards due to post-HD treatment fatigue. Participants in the SLEEP-HD study are undergoing thrice-weekly maintenance hemodialysis for &gt;3 months and have baseline Insomnia Severity Index scores &gt;10 with sleep disturbances &gt;3 nights/week for &gt;3 months. Participants randomized into the modified CBT-I protocol receive six weekly sessions, delivered by trained CBT-I therapists (1 MSW, 1 PhD) face-to-face via a HIPPA-compliant video telehealth platform. Participants keep a daily sleep diary throughout the CBT-I treatment period.

Results
To date, 91 patients (mean age=56.5 years [SD=14.7], 48.4% female) recruited from community-based dialysis facilities in Seattle and Albuquerque have been randomized into the SLEEP-HD study (n=31 CBT-I). Forty-eight percent of CBT-I clients have chosen to conduct their telehealth sessions during dialysis with the remainder choosing a different location. CBT-I adaptations include therapists developing weekly bed restriction recommendations based on non-dialysis treatment days; allowing shifts in dialysis day “bed window” scheduling for patients with very early or very late dialysis schedules so long as a consistent total time in bed in maintained; and including napping during early/late dialysis sessions as part of the allowable bed window duration. Treatment modifications were also designed to accommodate the diverse socioeconomic circumstances of dialysis patients, including housing instability, which can impact adherence to some standard stimulus control and bed restriction CBT-I recommendations.

Conclusion
It is feasible to deliver CBT-I via telehealth to HD patients but modifications to standard protocols are required.

Support (if any)
This work was supported by PHS grant 5R01AG053221.
384 Sleep, Pain, and Cognition in Women with Chronic Widespread Pain and Insomnia
Authors: Stephens Riley , Curtis Ashley , McCrae Christina S , McGovney Kevin 
Published: May 2021

Abstract

Introduction
Our team has shown pain interacts with sleep in its association with cognition in cardiac patients and older adults, such that better sleep is associated with better cognitive performance in individuals reporting high pain. Whether these associations exist in the context of chronic pain is unknown. This study examines these associations in women with chronic widespread pain and insomnia (CWPI) and extends our prior findings by including objective/subjective pain measures.

Methods
43 adult women (Mage=47.30, SD=13.93) with CWPI completed 14 daily diaries measuring wake time after sleep onset-WASO and total sleep time-TST. Daily diaries and thermal application [thermode on foot plantar] assessed subjective pain [0–100(most intense)]. Tender point testing assessed objective pain threshold [force(kg) on 18 tender points until painful]. Participants completed cognition tasks: Stroop (attention/processing speed) and Sternberg (working memory). Multiple regressions evaluated whether sleep (average WASO/TST) interacted with average subjective (diary/thermal ratings) and objective (force) pain in its association with cognition (Stroop reaction time (RT) on congruent trials/Sternberg #correct), controlling for age/education.

Results
WASO interacted with subjective pain (daily-B=.0003, SE=.0001, p=.009; thermal-B=.0002, SE=.004, p=.01) in its association with attention/processing speed. Higher WASO was associated with longer Stroop RT in high pain (~70/100) participants (B=.005, SE=.003, p=.047) and faster RT in low pain (~30/100) participants (B=-.009, SE=.004, p=.03). Higher WASO was associated with longer Stroop RT in those with high (~74/100; B=.01, SE=.002, p=.01), but not average (~46/100) or low (~19/100) thermal pain ratings (ps&gt;.05). TST interacted with daily pain in its association with attention/processing speed (B=.001, SE=.00, p=.005). In participants with high (B=-.003, SE=.001, p=.02), not average (~50/100) or low pain (~30/100, ps&gt;.05), longer TST was associated with faster Stroop RT. In those with low (~1kg, B=.07, SE=.02, p&lt;.001) and average (~2kg, B=.05, SE=.01, p=.002) pain thresholds, longer TST was associated with better Sternberg performance (trending interaction: B=-.03, SE=.02, p=.09).

Conclusion
In CWPI patients with high pain, better sleep was associated with better cognitive performance. These findings suggest sleep may hold potential to mitigate pain’s impact on cognition. Future studies should examine whether interventions that target sleep also improve cognition in chronic pain patients with high pain.

Support (if any)
NINR(R01NR017168)/ClinicalTrials.gov(NCT02001077), PI McCrae.
386 An Exploratory Study of Bedtime Procrastination and Emotional Regulation Strategies in Insomnia compared to healthy individuals
Authors: Kim Goeun , Nam Hyojin , Jeon Huisu , Suh Sooyeon 
Published: May 2021

Abstract

Introduction
Bedtime Procrastination (BP) is defined as the behavior of voluntarily delaying going to bed, without having external reasons for doing so. Recent research on procrastination behavior suggests that when negative emotions are elevated, procrastination behaviors can be triggered in order to find pleasure to avoid and alleviate them. Procrastination can also occur when there is difficulty regulating emotions. In addition, the reason for bedtime procrastination may be different depending on whether the individuals present with insomnia. According to previous studies, patients with insomnia may exhibit more pronounced negative avoidance of bedtime due to prolonged sleeplessness. Therefore, this study compared the difference between of the bedtime procrastination and the emotional regulation strategies between the insomnia group and the healthy group.

Methods
This study was conducted in 582 adults (mean age 23.06 ±2.16 years), 81.6% females. Individuals scoring higher than 15 on the Insomnia Severity Index (ISI) were classified into the insomnia group (n=375), and those less than 15 were classified into the healthy group (n=207). Participants completed the Bedtime Procrastination Scale (BPS), Emotional Regulation Strategies Checklist. Data was analyzed using descriptive statistics, chi square test, and independent t tests.

Results
The insomnia group had significantly higher bedtime procrastination scores than the healthy group (t=-6.241, p&lt;.001), and also the avoidant/distractive regulation style score was significantly higher (t=-1.969, p&lt;.05). In addition, the score of active regulation style was significantly lower in the insomnia group than in the healthy group (t=3.050, p&lt;.01). There was no significant difference between the two groups in the support-seeking regulation style.

Conclusion
Based on these results, it was confirmed that there was a difference in the bedtime procrastination and the emotional regulation strategies between the insomnia group and the healthy group.

Support (if any)
This work was supported by the Ministry of Education of the Republic of Korea and the National Research Foundation of Korea(NRF-2018S1A5A8026807)
388 Familial natural short sleepers have greater resilience than unaffected family members
Authors: Ashbrook Liza , Krystal Andrew , Fu Ying-Hui , Ptáček Louis 
Published: May 2021

Abstract

Introduction
Resilience, a life-long trait, corresponds to the ability to bounce back from adversity. What factors influence resilience is unclear. Here we describe a cohort of individuals with familial natural short sleep (FNSS). Four genes in five families have been identified that confer this trait, DEC2, NPSR1, GRM1 and ADRB1. Individuals in this cohort share a resilience phenotype alongside this decreased sleep need.

Methods
Those reporting less than 6.5 hours of sleep when allowed to sleep ad libitum without any complaints regarding overnight sleep or daytime sleepiness were then interviewed to determine FNSS affected status from 2009 to 2020. Data on mood, depression, sleepiness and resilience were collected from participants and family members enrolled in the FNSS study.

Results
163 individuals meeting criteria for FNSS were enrolled. Compared to 47 unaffected family members, they had significantly shorter sleep duration as measured by self report and actigraphy, significantly more resilience as measured by the Connor-Davidson Resilience Scale, significantly less sleepiness as measured by the Epworth Sleepiness Scale, and significantly fewer symptoms of depression as measured by the Beck Depression Inventory.

Conclusion
FNSS individuals appear to have a distinct phenotype including shorter sleep duration, greater resilience, less subjective sleepiness, and fewer symptoms of depression. Better understanding the genetics and characteristics of those with familial natural short sleep may provide insight into mechanisms of both restorative sleep and resilience.

Support (if any)
This work was supported by NIH grants NS099333, NS072360 and NS104782 to L.J.P. and Y-H.F., and by the William Bowes Neurogenetics Fund to L.J.P. and Y.H.F.
392 Effect of Obstructive Sleep Apnea Severity, Sleep Stage and Position on Patterns of Oximetric Desaturations and Resaturations
Authors: Thanaviratananich Sikawat , Cheng Hao , Pino Maria , Sundar Krishna 
Published: May 2021

Abstract

Introduction
Obstructive sleep apnea (OSA) severity based upon the apnea-hypopnea index (AHI) ignores many characteristics such as the duration of apnea-hypopneas, the duration and degree of oxygen desaturations (SpO2) etc. While hypoxemic burden has received increased attention given its relationship with cardiovascular outcomes, the role of oximetric resaturation vs. desaturation times is not understood. Resaturation times tend to be constant in contrast to desaturation durations. This study was done to assess desaturation and resaturation indices in patients with different OSA severity in differing sleep stages and positions.

Methods
Oximetric desaturation and resaturation slopes were calculated in patients with different OSA severities as rate of change in oxygen saturations (ΔSpO2/Δtime).

Results
33 patients with OSA were studied (11 in each OSA severity group). Mean desaturation duration was 20.12 ±1.10 seconds with shorter NREM desaturation times (mean 19.07 ±1.11 seconds) as compared to REM desaturation durations (mean 26.66 ±2.69 seconds) (p-value 0.009). Non-supine and supine mean desaturation durations were similar (19.59 ±1.77 and 18.73 ±1.18 seconds respectively). Mean resaturation durations were shorter than desaturation durations at 12.46 ±0.84 seconds and was significantly lower in NREM sleep than in REM sleep (9.32 ±0.41 seconds vs 12.50 ±0.75 seconds p-value 0.002). Resaturation slopes (0.44 %/second (±0.028 %/second)) were steeper as compared to desaturation slopes (-0.26 %/second (±0.02 %/second)) without significant difference between NREM vs. REM desaturation or resaturation slopes. While desaturation slopes were not affected by sleep position, resaturation slopes were significantly steeper in supine compared to non-supine sleep (p-value 0.0046). Desaturation durations increased with OSA severity, but resaturation times decreased (resaturation slopes became steeper) with significant differences between patients with different OSA severity.

Conclusion
This study demonstrated that oxygen resaturation slopes varied according to different OSA severity and sleep position. Given that faster resaturation rates may reflect the possibility of higher degrees of reoxygenation-related oxidative stress, this should be assessed as a novel index to predicate OSA outcomes.
Support (if any):