bluuebunny/crossref_metadata_2025_split huggingface dataset:
333 Associations Between Insomnia and Health Correlates in Nurses
Authors: Nagy Samantha , Dietch Jessica , Slavish Danica , Messman Brett , Ruggero Camilo , Kelly Kimberly , Taylor Daniel 
Published: May 2021

Abstract

Introduction
Insomnia, shiftwork (i.e., circadian rhythm disruptions) and insufficient sleep are common among nurses and healthcare workers. Each of these sleep problems can contribute to physical (e.g., inflammation, musculoskeletal pain, cardiovascular disease and heart rate variability, indigestion, and menstrual cycle irregularity) and mental (e.g., depression, anxiety, suicidality) health problems as well as daytime fatigue and sleepiness among nurses and may contribute to burnout and job change.

Methods
Participants (N=458) were nurses recruited for a parent study, “Sleep and Vaccine Response in Nurses (SAV-RN)” (Taylor & Kelly: R01AI128359-01). Most identified as female (90.5%), White/Caucasian (77.2%), and non-Hispanic (88.6%) with an average age of 39.03 (SD = 11.07). Participants completed baseline measures online via Qualtrics survey. The Sleep Condition Indicator (SCI; Espie et al., 2014) was used to identify a probable diagnosis of insomnia (score of ≤16 = Insomnia; endorsement of each of the primary DSM-5 criteria on the measure). In addition, a checklist of current major health conditions (high blood pressure, sleep apnea, GI issues, HIV/AIDS, cancer, etc.) was also completed. A Chi square test of Independence was conducted using SPSS to determine if insomnia detected by the SCI was associated with reported health conditions.

Results
At baseline, 25.4% of nurses had a probable insomnia diagnosis. Insomnia was associated with a greater likelihood of diagnosed sleep apnea, cancer (all types), high blood pressure, chronic pain, gastrointestinal problems, an autoimmune disease, and/or an endocrine problem at Month 11 of the study (all ps &lt;.05). Data cleaning is ongoing, but similar analyses will be presented examining shift work sleep disorder and insufficient sleep (i.e., average &lt; 6hrs per night) as individual and simultaneous predictors of physical and mental health at baseline and change from baseline to Month 11 (if available).

Conclusion
These results help to identify associations between insomnia and health conditions in nurses and may contribute to future research that supports evidence-based intervention and prevention strategies for this population. While evidence-based interventions for sleep disturbances and insomnia exist (CBT-I), accessibility and feasibility of scaling such interventions to reach the nursing community at large remains challenging.
Support (if any):
334 36 Month Surveillance Confirms Favorable Safety Profile of a Novel Continuous Release and Absorption Melatonin Delivery System
Authors: Corsino Patrick , Brodner David , Zeitzoff Linda 
Published: May 2021

Abstract

Introduction
The cumulative long-term effects of sleep loss have been associated with a wide range of damaging health consequences. There is a medical need for novel, non-pharmacological sleep aid alternatives. The ideal sleep solution would allow sleep to occur with normal sleep architecture and without causing dependence or daytime somnolence. Melatonin with its soporific effects and benign safety profile has been shown to be an effective sleep aid to decrease sleep onset latency, increase total sleep time and improve overall sleep quality. The novel, well tolerated CRA-melatonin, with the unique design of its delivery system, was shown in a randomized, crossover, pharmacokinetic (PK) study versus the leading marketed melatonin to achieve quick uptake and then continuous release and absorption for up to 7 hours. The REMfresh Safety Update at 36 months (REMSU36), a real world safety surveillance analysis was conducted to confirm the previously observed safety profile of CRA-melatonin.

Methods
An independent call center with pharmacovigilance-trained health care personnel, was retained to receive and record customer questions, product issues and adverse events (AEs). The data collection was conducted from March 9, 2017 to March 9, 2020. An estimated 981,735 adults used CRA-melatonin during the surveillance period.

Results
There were no serious AEs reported. Eighty-one (81) non-serious AEs were recorded, resulting in a 0.008% event reporting rate. The two most frequent AEs were headaches (7) and dizziness (5), which are also known comorbidities of chronic sleeplessness.

Conclusion
CRA-melatonin with its extended 7 hour PK profile may be an effective, well tolerated baseline therapy to improve sleep in adults These results, in a real world setting, support the previous reports of safety and tolerability of melatonin, as well as observed in the CRA-melatonin PK study.
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336 Effect of Lemborexant Versus Placebo and Zolpidem on REM Sleep by Quarter Night Intervals in Older Adults with Insomnia Disorder
Authors: Zammit Gary , Roth Thomas , Kumar Dinesh , Perdomo Carlos , Atkins Norman , Moline Margaret 
Published: May 2021

Abstract

Introduction
Effects of the dual orexin receptor antagonist lemborexant (LEM) on sleep architecture in adults ≥55y with insomnia disorder were assessed in Study E2006-G000-304 (Study 304; SUNRISE-1; NCT02783729). These post hoc analyses of Study 304 examined the acute effect of LEM on REM pressure (REM latency [REM-L] and REM by quarter of the night [QoN]).

Methods
This study was a 1mo, randomized, double-blind, placebo- and active-controlled (zolpidem tartrate extended-release 6.25mg [ZOL]) study of LEM (5mg, LEM5; 10mg, LEM10). Subjects received placebo (n=208), ZOL (n=263), LEM5 (n=266), or LEM10 (n=269). Two nights of PSGs were recorded at baseline, first 2 (N1/2), and last 2 (N29/30) treatment nights.

Results
Baseline REM-L (minutes) was similar across treatments (98.4–101.4). Significant decreases from baseline in REM-L were observed for LEM5 (−42.6 [53.9]) and LEM10 (−49.6[52.9]) vs placebo (−6.9[54.5]) and ZOL (0.2[54.2]) on N1/2 (all P&lt;0.0001). No difference was observed for ZOL vs placebo. Baseline REM (minutes) for each QoN was similar across treatments. In Q1, mean(SD) REM (minutes) on N1/2 was 16.5(9.7), 19.7(10.5), 10.3(8.2), and 8.5(7.6) for LEM5, LEM10, placebo, and ZOL, respectively. The difference was significant for LEM5 and LEM10 vs placebo and ZOL (all P&lt;0.0001), and ZOL vs placebo (P&lt;0.05). In Q2, mean(SD) REM on N1/2 was 19.2(9.4), 21.6(10.0), 17.9(8.9), and 17.2(9.3) for LEM5, LEM10, placebo, and ZOL, respectively. The difference was significant for LEM10 vs placebo (P&lt;0.0001) and for LEM5 and LEM10 vs ZOL (P&lt;0.01, P&lt;0.0001, respectively). No difference was observed for ZOL vs placebo. In Q3, mean(SD) REM on N1/2 was 23.3(10.3), 25.9(9.7), 20.8(9.4), and 22.8(9.9) for LEM5, LEM10, placebo, and ZOL, respectively. The difference was significant for LEM5, LEM10, and ZOL vs placebo (P&lt;0.01, P&lt;0.0001, P&lt;0.05, respectively) and LEM10 vs ZOL (P&lt;0.001). In Q4, mean (SD) REM on N1/2 was 23.8(9.4), 26.1(11.0), 21.6(10.9), and 22.5(10.1) for LEM5, LEM10, placebo, and ZOL, respectively. The differences were significant for LEM5 and LEM10 vs placebo (P&lt;0.05, P&lt;0.0001, respectively), and for LEM10 vs ZOL (P&lt;0.0001). Generally, similar findings were noted at N29/30; these data will be reported.

Conclusion
LEM, but not ZOL, acutely increases REM pressure as evidenced by REM latency and REM duration per quarter.

Support (if any)
Eisai Inc.
338 How Much Improvement in the Insomnia Severity Index Is Associated With a Positive Impact of A Patient’s Insomnia Medication?
Authors: Lenderking William , Savva Yulia , Chabot Isabelle , Meier Genevieve , Yardley Jane , Moline Margaret 
Published: May 2021

Abstract

Introduction
In Phase 3 Study 304 (SUNRISE-1; NCT02783729) and Study 303 (SUNRISE-2; NCT02952820), 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. Both studies included the Insomnia Severity Index (ISI) and the Patient Global Impression–Insomnia version (PGI-I). On the PGI-I scale, subjects assess positive, neutral or negative treatment impact on falling asleep, overall benefit on sleep, and total sleep time. Using an anchor-based approach, ratings were compared with mean changes in ISI scores from baseline to evaluate what would be considered a responder definition on the ISI.

Methods
Study 304 was a 1mo, randomized, double-blind, placebo- and active-controlled, parallel-group study in female (age ≥55y) and male (age ≥65y) subjects (n=1006); subjects received placebo, LEM 5mg, LEM 10mg, or zolpidem tartrate extended-release. Study 303 was a 12mo, randomized, double-blind study in subjects age ≥18y (n=950). Subjects received placebo, LEM 5mg, or LEM 10mg for 6mo. Data from both studies were pooled for the first month of treatment across all treatment groups. A modified ISI total score (ISI-ts) was used based on a confirmatory factor analysis that showed no incremental value to including Question 5 (How NOTICEABLE to others do you think your sleep problem is in terms of impairing the quality of your life?).

Results
The ‘Overall Sleep’ PGI-I item demonstrated that mean [SD] changes from baseline in ISI-ts decreased more in association with self-reported positive effects (−8.15 [4.98]) than for neutral (−3.59 [3.37]) or negative effects (−1.67 [2.91]) at Day 31/Month 1. For PGI-I Item ‘Time to Fall Asleep,’ mean (SD) changes from baseline in ISI-ts were −7.49 (5.10) for positive, −4.54 (4.13) for neutral, and −2.94 (4.04) for negative effects at Day 31/Month 1. For PGI-I Item ‘Total Sleep Time’ mean (SD) changes from baseline in ISI-ts were −8.15 (5.04) for positive, −3.74 (3.23) for neutral, and −2.40 (3.49) for negative effects at Day 31/Month 1.

Conclusion
Results of this anchor-based approach using the PGI-I suggest that the responder definition for ISI-ts, using the modified ISI, should be approximately −8 points.

Support (if any)
Eisai Inc.
342 CBT-I Has Sustained Effects on Insomnia Versus Heart-Failure Self-Management Education among Adults with Chronic Heart Failure
Authors: Redeker Nancy , Bessette Andrew , Breazeale Stephen , Conley Samantha , Hollenbeak Christopher , Hwang Youri , Iannacco Joanne , Jacoby Daniel , Kelly-Hauser Jessica , Linsky Sarah , Moemeka Lesa , Nwanaji-Enwerem Uzoji , O’Connell Meghan , Yaggi Henry , Jeon Sangchoon 
Published: May 2021

Abstract

Introduction
Insomnia is common among adults with chronic heart failure (HF), often not explained by sleep apnea (SA), and associated with daytime symptoms and poor daytime function. The purpose of this randomized controlled trial was to evaluate the sustained effects of cognitive behavioral therapy for insomnia (CBT-I) on insomnia severity and sleep characteristics over 6 months among adults with stable chronic HF.

Methods
We included adults with HF who had at least mild insomnia [Insomnia Severity Index (ISI) &gt; 8] and no more than mild SA or SA treated with continuous positive airway pressure. We randomized in groups to 8 weeks of group CBT-I (Healthy Sleep: HS) [4 group sessions + calls on alternate weeks] or attention control (Healthy Hearts: HH) [HF self-management education + brief sleep hygiene] in the same format. We administered the ISI, the Pittsburgh Sleep Quality Index (PSQI), the Dysfunctional Beliefs & Attitudes about Sleep Scale (DBAS), and the Sleep Disturbance Questionnaire (SDQ) at baseline (T0), 2 weeks after treatment ended (T1) and at 6 months (T2). Statistical analysis included descriptive statistics and mixed effects models with random intercepts and slopes.

Results
The sample include 175 participants (HS: N = 91; 62 + 13 years; 58% Male; 15% Black; 68% NY Heart Class II-III) (HH: N = 84; 64 + 12.5 years; 56% Male; 17% Black; 70% NY Heart Class II-III). There was no significant difference at baseline in demographic characteristics or the mean ISI [HS: 15.3 (4.5); HH: 14.4 (4.5)], but a greater percentage in the HS group had clinical/moderate-severe insomnia (ISI &gt; 15) (HS: 60.4% vs. HH: 47%). The CBT-I intervention (HS) was associated with significant improvement in insomnia severity (ISI: p = .001), sleep quality (PSQI: p = .002), and sleep-related cognitions (DBAS: p = .0006; SDQ: p = .0138), and a modest effect on self-reported sleep duration (46 vs. 20 mins, p = .054), but no effect on sleep efficiency. At 6 months, 12.9% of the HS group, compared with 24.9% of the HH group had clinical insomnia.

Conclusion
CBT-I has sustained effects on insomnia, sleep-quality, and sleep-related cognitions in people with HF.

Support (if any)
R01NR01691 (NSR, PI)
344 Daridorexant Improves Total Sleep Time (TST) in Insomnia Patients Without Altering the Proportion of Sleep Stages
Authors: Zammit Gary , Mayleben David , Fietze Ingo , Pain Scott , Kinter Dalma Seboek , Gimona Alberto , Dauvilliers Yves 
Published: May 2021

Abstract

Introduction
Daridorexant, a new dual orexin receptor antagonist, improved sleep parameters and daytime functioning in two pivotal Phase 3 trials in patients with insomnia (Trial-1, NCT03545191; Trial-2, NCT03575104); polysomnography data were collected at multiple timepoints from &gt;1,800 patients. We report the effects of daridorexant on TST and sleep stages from both trials.

Methods
Eligible patients with insomnia (according to DSM-5) were randomized (1:1:1) in Trial-1 (N=930) to daridorexant 25mg, 50mg, or placebo and in Trial-2 (N=924) to daridorexant 10mg, 25mg, or placebo. Oral treatment was administered each night during a 3-month double-blind treatment period. Assessment of TST and sleep stages (non-rapid eye movement [NREM, N]1, N2, N3, REM), measured by polysomnography in sleep laboratory, was performed on two consecutive nights during single-blind placebo run-in (baseline) and Months 1 and 3 (M1 and M3) of double-blind treatment. Change from baseline in TST and sleep stages were exploratory endpoints in both trials. Data for M3 (mean ± standard deviation) are presented as change from baseline.

Results
Daridorexant dose-dependently increased TST(minutes) from baseline to M3, more than placebo, in Trial-1 (25mg, 55±56; 50mg, 61±53; placebo, 40±56) and Trial-2 (10mg, 37±57; 25mg, 50±53; placebo, 35±56). In both trials, sleep stage proportions were preserved from baseline to M3, with no relevant changes in any group. Baseline time spent in each sleep stage (% of TST) was consistent across groups in both trials (range across treatment groups in both trials: N1:11–13; N2:55–57; N3:11–14; REM:19–20). In Trial-1 (25mg/50mg/placebo), the change from baseline to M3 in % of TST spent in N1(-0.3±4.7/-0.2±5/0.1±5), N2(2±8/1±7/1±7), N3(-2±6/-2±6/-2±6), and REM(1±6/1±5/1±5) was low and numerically similar across treatments. In Trial-2, the change from baseline to M3 in % of TST spent in each sleep stage was consistent with Trial-1, with no effect of dose. Mean changes from baseline (% of TST) for each sleep stage appeared to be independent from increasing TST. Data for 25mg were consistent between trials.

Conclusion
Daridorexant at any dose, and each more than placebo, increased TST in a dose-dependent manner without affecting the proportion of all sleep stages in patients with insomnia.

Support (if any)
Funded by Idorsia Pharmaceuticals Ltd.
346 Semi-Individualized Acupuncture for Insomnia Disorder: A Randomized Sham-Controlled Trial
Authors: Yeung Jerry Wing-Fai , Yu Branda Yee-Man , Yuen John , Ho Janice , Chung Ka-Fai , Zhang Zhang-Jin , Mak Deejay Suen-Yui , Suen Lorna Kwai-Ping , Ho Lai Ming 
Published: May 2021

Abstract

Introduction
Acupuncture is an alternative treatment for improving sleep quality and the effectiveness is thought to be optimized with an individualized approach resembling real practice. However, existing evidence is limited by methodological shortcomings due to blinding issues, standardized measures, and diagnostic procedures. It was of the present study’s interest to examine the efficacy and safety of semi-individualized acupuncture treatment on insomnia.

Methods
Adults with DSM-5 insomnia disorder (n = 140) were randomized with 1:1 allocation to a 4-week intervention traditional acupuncture (TA) or validated non-invasive sham acupuncture (SA). The selection of acupoints was semi-individualized by the acupuncturist. As the primary outcome, the sleep efficiency (SE) by sleep diary was assessed at baseline, 1-week posttreatment, and 5-week posttreatment. Other sleep parameters derived from sleep diary, the wrist-actigraphy-derived sleep parameters, insomnia symptom severity, anxiety, and depressive symptoms, as well as the health-related quality of life, were also evaluated.

Results
Although linear mixed-effect model revealed both groups did not attain significant difference in sleep-diary-derived SE and other outcome measures (all P &gt; 0.05), TA promising effect on improving insomnia symptom (within-group effect size, d = 1.13 & 1.30 at 1-week & 5-week posttreatment respectively) and also a higher proportion of subjects achieved SE ≥ 85% compared with SA (55.6% versus 36.4% at week 9, P = 0.03). Besides, subjects in TA group reported significantly greater improvement in both the total sleep time (TST) derived from sleep diary and actigraph than those in the SA group at 1-week posttreatment (difference in mean changes from baseline: sleep diary = 22.0 min, p = 0.01; actigraphy =18.8 min, P = 0.02) but not 5-week posttreatment.

Conclusion
This study is the first to evaluate the effect of the TCM-theory-based individualized acupuncture on sleep using a sham-control design. A 4-week semi-individualized acupuncture is able to significantly increase total sleep time with few adverse events.

Support (if any)
Research Grants Council of Hong Kong, Early Career Scheme (Project no.: 25101017)
347 Daridorexant is Safe and Improves Both Sleep and Daytime Functioning in Elderly Patients with Insomnia
Authors: Fietze Ingo , Bassetti Claudio , Mayleben David , Gimona Alberto , Pain Scott , Kinter Dalma Seboek 
Published: May 2021

Abstract

Introduction
Insomnia affects elderly more than younger adults, and comorbidities more prevalent in elderly populations can add to symptom burden and reduce therapeutic options. Drugs that improve insomnia symptoms with limited safety risks are needed to treat this patient group. We report elderly subgroup analyses from a Phase-3 registration trial with daridorexant.

Methods
In this multi-center, double-blind trial (NCT03545191), adult (18–64y) and elderly (≥65y) patients with insomnia were randomized (1:1:1) to receive oral daridorexant 25mg, 50mg or placebo every evening for 3 months. Month 3 endpoints were: change from baseline in polysomnography-measured wake-after-sleep-onset (WASO) and latency-to-persistent-sleep (LPS) (both primary endpoints), subjective total sleep time (sTST), and daytime functioning (Insomnia Daytime Symptoms and Impacts Questionnaire [IDSIQ] – sleepiness domain; with a lower score indicating improved daytime functioning). Safety endpoints included treatment emergent adverse events (TEAE), AEs of special interest (AESI; symptoms related to excessive daytime sleepiness or complex sleep behavior, and suicidal ideation/self-injury) and withdrawal effects upon treatment cessation (assessed by the Benzodiazepine Withdrawal Symptom Questionnaire total score and relevant AEs).

Results
Of the 930 patients randomized, 364 (39.1%) were ≥65y: daridorexant 25mg (n=121), 50mg (n=121) and placebo (n=122). In this subgroup, at Month 3, the placebo-corrected least-square mean of change from baseline [95%CL] for daridorexant 25mg and 50mg were: WASO -17.0[-27.0,-7.0] and -19.6[-29.5,-9.7] mins; LPS -7.8[-15.2,-0.4] and -14.9[-22.3,-7.5] mins; sTST 18.7[4.1,33.2] and 30.6[16.1,45.2] mins; IDSIQ sleepiness domain -0.6[-2.2,0.9] and -2.6[-4.1,-1.0], all respectively. TEAEs were reported in 32.2%, 35.3%, and 31.1% of patients ≥65y in the 25mg, 50mg and placebo groups, respectively. Falls (n=1,1,4 for 25mg, 50mg, placebo, respectively) and dizziness (n=4,1,1), both of particular interest in elderly, were least frequent in the 50mg group. Compared to placebo, somnolence was as frequent for 50mg daridorexant (n=6,1,1) while fatigue was more frequent in both daridorexant groups (n=4,3,1); incidence did not appear dose-related. AESI, of mild intensity, were reported in 2 patients ≥65y (one in each daridorexant group). There was no evidence of withdrawal symptoms.

Conclusion
Daridorexant is efficacious in the elderly population for improvements in sleep and daytime functioning. No safety concerns in this vulnerable population were identified at either dose.

Support (if any)
Funded by Idorsia Pharmaceuticals Ltd.
356 Examining Use and Beliefs about Sleep Medications in a Sample of Older Adults: The Role of Hypnotic Dependency
Authors: Tully Isabelle , Simpson Norah , Dietch Jessica , Tutek Joshua , Manber Rachel 
Published: May 2021

Abstract

Introduction
Prevalence of insomnia and prescription of sleep medications increases in older adults and is associated with heightened risk of falls, cognitive and psychomotor detriments, and exacerbation of pre-existing conditions. The present study aimed to characterize beliefs about sleep and sleep medications, hypnotic self-efficacy, and hypnotic dependence in a sample of older adults with insomnia disorder.

Methods
Adults 50 years and older (N = 141) who met DSM-5 criteria for insomnia disorder were enrolled in the RCT of the Effectiveness of Stepped-Care Sleep Therapy In General Practice (RESTING) study. At baseline, participants completed the Beliefs about Medications Questionnaire (BMQ; subscales assess the belief that hypnotics are necessary and concern regarding consequences of use), Insomnia Severity Index (ISI), Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS), Pre-Sleep Arousal Scale (PSAS), and the Patient Health Questionnaire-4 (PHQ-4). Participants taking prescription sleep medications (n = 54) also reported if they had sedative hypnotic reduction goals and completed the Sleep Medications Dependency Scale and Hypnotic Self-Efficacy Scale.

Results
Those taking prescription sleep medications reported greater belief in the necessity of sedative hypnotics (p &lt; .001, d = 1.69) and greater anxiety and depression (p = .005, d = .57) than those not taking prescription medications; groups did not differ significantly on the BMQ concern subscale, ISI, DBAS, or PSAS. 70.4% of participants using prescription sleep medications endorsed decrease in sedative hypnotic use as a treatment goal. Dependency on sleep medications, but not hypnotic self-efficacy, was greater in those with this goal (p = .003, d = .94). Higher levels of hypnotic dependence were associated with both greater concern (r = .40, p = .003) and belief in the necessity of sleep medications (r = .48, p &lt; .001).

Conclusion
Our findings indicate that many treatment-seeking older adults with insomnia disorder take prescription sleep medications. They tend to believe in the necessity of sleep medications for controlling sleep disruption, but also identify medication reduction as a treatment goal, even if endorsing dependence on hypnotics. This highlights the importance of disseminating non-medication treatments that address both insomnia and reduction of sedative hypnotic use.

Support (if any)
1R01AG057500