bluuebunny/crossref_metadata_2025_split huggingface dataset:
0474 Long-Term Efficacy and Safety of Lemborexant in Elderly Adults with Insomnia Disorder: Results from SUNRISE-2
Authors: Moline M , Inoue Y , Pinner K , Perdomo C , Filippov G , Kubota N , Yardley J 
Published: May 2020

Abstract

Introduction
In SUNRISE-2 (NCT02952820; E2006-G000-303), the dual orexin receptor antagonist lemborexant (LEM) demonstrated significant benefit versus placebo (PBO) on subjective sleep endpoints over 6mo in subjects age ≥18y; benefits were sustained over 12mo. Here we present 12mo efficacy and safety data for LEM from the elderly (≥65y) subgroup.

Methods
SUNRISE-2 was a 12mo, randomized, double-blind, PBO-controlled (first 6mo [Period 1]), global phase 3 study. During Period 1, subjects were randomized to PBO or LEM (5mg, [LEM5]; 10mg, [LEM10]). During Period 2 (second 6mo), LEM subjects continued their assigned dose while PBO subjects were rerandomized to LEM5 or LEM10 (not reported here). Patient-reported (subjective) sleep endpoints were assessed from sleep diary data (sleep onset latency [sSOL]; sleep efficiency [sSE]; wake after sleep onset [sWASO]).

Results
Of the 949 subjects in the Full Analysis Set, 262 were age ≥65y. At 6mo, in subjects ≥65y, median sSOL significantly decreased from baseline for LEM5 (−21.7) and LEM10 (−26.0) versus PBO (−10.8; P&lt;0.0001, P&lt;0.01, respectively). At 12mo, LEM5 and LEM10 subjects maintained decreases in median sSOL (−29.3, −34.3, respectively). At 6mo, the mean (SD) increase from baseline in sSE was significantly larger versus PBO (8.5[13.3]) for LEM5 (16.9[13.6]; P&lt;0.001) and LEM10 (14.9[15.9]; P&lt;0.01). At 12mo, mean (SD) increase in sSE was maintained for LEM5 (18.1[12.5]) and LEM10 (18.0[16.8]). At 6mo, mean (SD) change from baseline in sWASO was significantly decreased versus PBO (−26.5 [52.9]) for LEM5 and LEM10 (−54.8[64.4], P&lt;0.01; −51.4[69.3], P&lt;0.05, respectively). At 12mo, mean (SD) decrease in sWASO was maintained for LEM5 (−58.6[46.0]) and LEM10 (−60.9[80.4]). Over 12mo, the most common (&gt;10% either group) treatment emergent adverse events with LEM5 and LEM10, respectively, were somnolence (9.3%, 19.0%), nasopharyngitis (9.3%, 10.7%), and headache (10.5%, 6.0%).

Conclusion
In elderly subjects, LEM demonstrated efficacy at 6mo, which persisted at 12mo; LEM was well tolerated.

Support
Eisai Inc.
0500 Evaluation of the Human Abuse Potential of Single Oral Doses of V117957, a Novel, Highly Potent and Selective Partial Agonist for Nociceptin/Orphanin-FQ Peptide (NOP) Receptors
Authors: Harris S , Zhou M , Cipriano A , Kapil R , Shet M , He E , Apseloff G 
Published: May 2020

Abstract

Introduction
The satisfactory safety/tolerability profile of V117957, an investigational NOP receptor partial agonist, has been previously established in ~200 healthy subjects with maximum doses at 30mg following a single oral administration and 10mg once daily for 2 weeks. V117957 exhibited linear plasma exposures at doses up to 10mg. In patients with insomnia disorder, V117957 demonstrated dose-dependent improvement in sleep efficiency and sleep maintenance between 0.5mg and 10mg as measured by polysomnography and patient diaries. The current study evaluated the abuse potential and safety of V117957 in healthy, nondependent recreational polydrug users with a history of central nervous system (CNS) depressant use.

Methods
The abuse potential of V117957 (1mg, 6mg, 10mg), placebo, and triazolam (0.5mg, 1mg) were assessed in a randomized, double-blind, double-dummy, placebo- and positive-controlled crossover study. Triazolam was utilized as a positive control based on its comparable pharmacokinetic and pharmacodynamic characteristics. V117957 doses (1mg, 6mg, 10mg) were selected to represent therapeutic, mid-range supratherapeutic, and maximum-tolerated supratherapeutic doses, respectively. Subjects were qualified based on pharmacodynamic responses following a single oral 0.75mg triazolam dose. Drug liking was measured through 24 hours, including the primary endpoint of maximum “at the moment” Drug-Liking Visual Analog Scale, as recommended by FDA. Secondary endpoints included Divided Attention Test (DAT) and Choice Reaction Time (CRT).

Results
The positive control (triazolam 0.5mg, 1mg) produced statistically significant greater abuse potential and cognitive/motor impairment versus placebo, which demonstrated study validity. In contrast, V117957 at 1mg was not statistically significantly different from placebo. At the supra-therapeutic doses of 6 and 10mg, V117957 was associated with abuse potential and cognitive/motor impairment greater than placebo, yet similar to those of triazolam 0.5 and 1mg.

Conclusion
Overall, in this valid study, V117957 1mg and placebo were associated with statistically significant lower potential for abuse and reduced cognitive/motor impairment compared with the two supratherapeutic doses of V117957 (6mg, 10mg), and triazolam (0.5mg, 1mg). V117957 1mg met FDA’s statistical criterion for similarity to placebo.

Support
Funded by Imbrium Therapeutics, a subsidiary of Purdue Pharma L.P.
0510 The Apnea and Insomnia Research (AIR) Trial: A Preliminary Report
Authors: Edinger J D , Manber R 
Published: May 2020

Abstract

Introduction
Many sleep apnea patients suffer from comorbid insomnia disorder. Although cognitive behavioral insomnia therapy (CBTI) is recommended as the first line insomnia treatment for such patients, access to trained providers of this treatment remains limited. The current study is testing he efficacy of an online CBTI among CPAP treated sleep apnea patient with comorbid insomnia.

Methods
Patients enrolled in this trial complete baseline measures and then are randomized to either an online version of Cognitive Behavioral Insomnia Therapy (CBTI) or no additional treatment beyond their CPAP therapy (CTRL). After 8 weeks of treatment all patients are reassessed. The current report considers changes in scores on the ISI and Epworth Sleepiness Scale (ESS) as well as average minutes of nightly CPAP use from pre-treatment to the end of the initial 8 weeks of online treatment relative to the no treatment CTRL. The sample for this report included the first 170 participants enrolled in this trial (mean age = 56.5±12.5 yrs; 60.1% females).

Results
Those receiving online CBTI showed greater reductions in their ISI scores from baseline to the end of the initial 8-week treatment phase than did those in the CTRL group (p = .0009). Average ISI score improvements among those receiving online CBTI moved patients from moderately severe insomnia to mild insomnia symptoms. In contrast, no differences were noted between the online CBTI and CTRL groups in regard to pre- to post-treatments changes on the ESS (p= .3771) scores or amount of CPAP use (p = .8053).

Conclusion
Whereas online CBTI does not seem to reduce daytime sleepiness or improve CPAP adherence among patients with comorbid sleep apnea and insomnia, it appears to be an effective intervention for reducing insomnia severity for this patient group.

Support
National Heart. Lung and Blood Institute Grant # 1R01HL130559-01A1
0525 Subtypes of Efficacy of Cognitive-Behavioral Therapy for Insomnia
Authors: Castronovo V , Sforza M , Galbiati A , Salsone M , Marelli S , Ferini-Strambi L 
Published: May 2020

Abstract

Introduction
Cognitive-Behavioral Therapy for Insomnia (CBT-I) is the ﬁrst-line treatment for Insomnia disorder (ID). We aimed to identify ID patients’ subtypes based on clinical features and their response to CBT-I.

Methods
294 chronic insomnia patients (61.6% female, mean age 40.7 ± 12.3 yrs) underwent 7-sessions group CBT-I. By use of latent class analysis (LCA) we identified insomnia disorder subtypes according to baseline (BL) evaluation of non-sleep indices and the response to CBT-I (Delta score of Insomnia Severity Index ISI between BL and end-of-treatment (ET). Moreover, we assessed ISI in 123 out of 294 insomnia patients (82 females (66.7%), mean age 40.59 ± 11.89 years) who completed a follow-up evaluation (FU) within a range of 4-10 years.

Results
We chose 3 latent classes as most parsimonious model. We identified Class 1 (insomnia+anxiety+depression+stress) (n=62), Class 2 (insomnia+anxiety+depression) (n=153) and Class 3 (only-insomnia) (n=79). The effect of CBT-I was maintained up to 10 years after the ET in the three classes but with significant difference between classes (p&lt;0.05). At the ET, the largest percentage of responders (ISI decrease ≥ 8) was found in Class 1 (63.5%). Results of overall CBT-I effectiveness: in Class 3, 98.6% had subthreshold insomnia (ISI score=0-14) at the ET, and 97.2% at the FU; in Class 2, 89.0% at the ET, and 78.2% at the FU; in Class 1, 80.7% at ET and 51.8% at the FU.

Conclusion
Our analysis identified three different subtypes of insomniacs on the basis of clinical outcomes. The presence of anxiety and depression did not diminish the effect of CBT-I both short and long term. However, ID patients characterized by the presence of stress (Class 1) were the best responders at the ET but this was not maintained at the FU evaluation. We can speculate that stress could be considered a risk factor that plays an important role in the long-term outcome of CBT-I.

Support
No
0527 The Uptake of a Free Digital CBTi Programme in a Large Commercial Organisation
Authors: Gardiner A , Stanley N 
Published: May 2020

Abstract

Introduction
CBTi is effective in the treatment of insomnia and is now recommended as the first-line treatment. However, despite the desirability of CBTi, access to therapy is restricted due to the lack of sufficient appropriately trained and experienced therapists. Because of the lack of therapists and the financial and time costs associated with face to face therapy a number of programmes that offer CBTi digitally have been developed, which have been shown to have similar success rates to receiving therapy in person.

Methods
The uptake of Sleepstation www.sleepstation.org.uk, a clinically proven CBTi platform with additional human support, was investigated when it was offered free to the members of a large organisation in the UK. The availability of the programme was promoted via the organisation’s website for 3 months.

Results
1173 people registered an interest in the programme of which 880 were assessed for suitability (73% female, median age 45yrs). 411 where offered treatment due to symptoms indicative of insomnia. 188 initiated treatment. 137 complete the programme or reached recovery. 112 showed an improvement in their sleep.

Conclusion
Simply reporting the success rate of CBTi only tells part of the story. Simply improving access to CBTi, whether face to face or digitally, does not necessarily improve the initiation, retention, and completion of CBTi therapy. Further research is needed to fully understand the real and perceived barriers to the use of CBTi.

Support
This study was facilitated by Sleepstation
0539 Are Short Sleepers Uncoupled Sleepers?
Authors: Hartescu I , Morgan K , Stensel D J , Thackray A E , King J A 
Published: May 2020

Abstract

Introduction
While short sleep durations (&lt;7h/night) are associated with increased diabetes risk, there is limited evidence that increasing the habitual sleep duration of short sleepers is either feasible, or will reliably improve metabolic health outcomes. Furthermore, in the absence of insomnia disorder, it remains unclear whether habitual short sleep mainly reflects a genetic predisposition or a lifestyle choice. In a randomized controlled study we delivered a sleep extension protocol based on CBTi principles to overweight ‘short sleepers’ at increased risk of Type II diabetes.

Methods
18 male short sleepers (Mage=41.4; MBMI=29.57; baseline mean TST=5.8 h/ night) with no complaints of insomnia were randomized to the sleep extension intervention or control condition (printed sleep hygiene advice). The 6-week intervention commenced with personalized sleep re-scheduling negotiated in a 60-minute 1-to-1 session, and supported by elements of sleep hygiene, stimulus control, relaxation and cognitive strategies. Outcomes included sleep duration (actigraphy), fasting insulin, Mean Amplitude of Glycemic Excursions (MAGE) from continuous glucose monitoring, and blood pressure. Data were analyzed in linear fixed effects models including time, group and baselines values.

Results
Adherence to the 6-week protocol was high. Relative to controls (n=8), intervention participants (n = 10) showed a significant increase in TST (95%CI 46.91min, 101.64min, p&lt;0.001; MDiff = 79.4min, p&lt;0.001) and significant reductions in fasting insulin (95%CI -32.08 pmol/L, -.97.0 pmol/L; p=0.04; MDiff = -10.2 pmol/L, p=0.06); MAGE (95%CI -0.77, -0.08, p=0.02; MDiff -0.35, p=0.05) and diastolic (95%CI -22, -5, p=0.004; MDiff=-12, p=0.004); and systolic blood pressure (95%CI -20, -2, p=0.03; MDiff=-10, p=0.006).

Conclusion
CBTi-based sleep extension protocols offer feasible and effective lifestyle interventions in the management of metabolic health in overweight short sleepers who fit published categorization of non-complaining poor sleepers with an undeveloped insomnia identity whose subjective sleep experience and objective sleep characteristics are ‘uncoupled’.

Support
School of Sport, Exercise and Health Sciences, Loughborough University
0552 Investigating Pre-Sleep Processes and How They Influence Sleep: A Diary and Actigraphy Study
Authors: Maeder T , Whitford J , Feinaigle P , Karlen W , Seifritz E , Pace-Schott E F , Kleim B 
Published: May 2020

Abstract

Introduction
The current study examined the relationship between pre-sleep processes and sleep in the context of real-world stress exposure in medical students during an internship. Medical students are often exposed to a variety of stressors and potentially traumatic events and have been shown to be at risk to develop psychopathology. Previous research has shown an association between stress, psychological distress, and sleep disturbances. In this context, studies have investigated possible predictors for sleep disturbances. Recently, the period just prior to sleep onset has received increased interest. At the moment, little is known, however, about the influence of such pre-sleep processes. In this study, we investigated the influence of pre-sleep rumination and mindfulness on sleep disturbances.

Methods
In a prospective study, we examined a sample of 50 medical students from the University of Zurich. All participants completed their first medical internship over 9 months as part of medical school. Pre-sleep processes and sleep were indexed mid-internship using sleep diaries over seven consecutive days. Additionally, a Fitbit tracking device was used to objectively measure sleep. Correlational analyses and multilevel linear models were conducted.

Results
Results show associations between pre-sleep processes and sleep disturbances in this stress-exposed at-risk population. Multilevel mixed-effects models showed that over the period of 7 consecutive nights, pre-sleep rumination was a significant predictor of lower subjective sleep quality (B = -.085, SE = .036, p = .02), lower subjective total sleep time (B = -.124, SE = .043, p = .005), higher subjective sleep onset latency (B = 1.535, SE = .678, p = .025), and higher subjective wake-up frequency (B = .033, SE = .011, p = .003).

Conclusion
Together, our data suggest pre-sleep processes as potential targets for stress-prevention programs that could help reduce the negative influence of stress in at risk populations.

Support
NA
0559 Association of Rapid Eye Movement Sleep with Insulin Resistance in Han Chinese Patients With Obstructive Sleep Apnea
Authors: Zhang C , Xu H , Zou J , Guan J , Yi H , Yin S 
Published: May 2020

Abstract

Introduction
Obstructive sleep apnea (OSA) is increasingly associated with insulin resistance. The underlying pathophysiology remains unclear but rapid eye movement (REM) sleep has been hypothesized to play a key role. To investigate the associations of insulin resistance with respiratory events and sleep duration during REM sleep, 4,062 Han Chinese individuals with suspected OSA were screened and 2,899 were analyzed.

Methods
We screened 4,062 participants with suspected OSA who underwent polysomnography in our sleep center from 2009 to 2016. Polysomnographic variables, biochemical indicators, and physical measurements were collected. Logistic regression analyses were conducted to determine the odds ratios (ORs) and 95% confidence intervals (95% CIs) for insulin resistance as assessed by hyperinsulinemia, the homeostasis model assessment of insulin resistance (HOMA-IR), fasting insulin resistance index (FIRI), and Bennet’s insulin sensitivity index (ISI).

Results
The final analyses included 2,899 participants. After adjusting for age, gender, body mass index, waist circumference, mean arterial pressure, smoking status, alcohol consumption, and the apnea and hypopnea index during non-REM sleep (AHINREM), the results revealed that AHI during REM sleep (AHIREM) was independently associated with insulin resistance; across higher AHIREM quartiles, the ORs (95% CIs) for hyperinsulinemia were 1.340 (1.022, 1.757), 1.210 (0.882, 1.660), and 1.632 (1.103, 2.416); those for abnormal HOMA-IR were 1.287 (0.998, 1.661), 1.263 (0.933, 1.711), and 1.556 (1.056, 2.293); those for abnormal FIRI were 1.386 (1.048, 1.835), 1.317 (0.954, 1.818), and 1.888 (1.269, 2.807); and those for abnormal Bennet’s ISI were 1.297 (1.003, 1.678), 1.287 (0.949, 1.747), and 1.663 (1.127, 2.452) (P &lt; 0.01 for all linear trends). Additionally, the results showed that for every 1-h increase in REM duration, the risk of hyperinsulinemia decreased by 22.3% (P &lt; 0.05).

Conclusion
The present study demonstrated that AHIREM was independently associated with hyperinsulinemia and abnormal HOMA-IR, FIRI, and Bennet’s ISI. Additionally, REM sleep duration was independently associated with hyperinsulinemia.

Support
This study was supported by Grants-in-aid from Shanghai Municipal Commission of Science and Technology (No.18DZ2260200).
0561 Differences in Nasopharyngoscopic Airway Form Between Awake and Sleep, Sitting and Recumbent Position and Techniques
Authors: Nishimura Y , Hamed M 
Published: May 2020

Abstract

Introduction
To examine and compare the information derived from flexible fiber-optic nasopharyngoscopy in awake mimic snoring (AMS), Müller’s Maneuver (MM) and drug-induced sleep endoscopy (DISE), to determine if AMS and MM can be used in substitution for DISE as a streamlined method. We investigated their relation with the level and pattern of obstruction detected on AMS, MM and DISE.

Methods
This is a retrospective study of 15 obstructive sleep apnea patients with apnea hypopnea index from 8.3 to 105.2, ages 20 to 80 were included. Each patient underwent polysomnography and thorough a physical examination, including flexible nasopharyngoscopy with AMS, MM and DISE. Airway obstruction on these endoscopic procedures were described according to airway level and pattern of obstruction. They were classified 5 different types; Uvula type: anterior-posterior vibration of the uvula, no airway obstruction; L-R velum type: lateral (the left and right directions) airway narrowing at velum level, no airway obstruction; A-P velum type: anterior-posterior total airway obstruction at velum level; Tonsillar type: total airway obstruction at pharyngeal level; Circumferential type: circumferential total airway obstruction at velum level. AMS and MM were performed with patients in sitting and in recumbent position. DISE was performed only in recumbent position.

Results
In review of the three procedures, the results were much different. Airway was obstructed in all cases(100%, 15 of 15)in DISE, but not all cases in AMS and MM. When tonsillar type was seen in AMS, it was also seen in MM and DISE(100%, 5 of 5).

Conclusion
Flexible fiber-optic nasopharyngoscopy appears to be useful for evaluating airway obstruction. It might be not suitable to use AMS and MM in substitution for DISE(except tonsillar type). Muscle tonic relaxation of the upper airway between AMS, MM and DISE might be different (DISE&gt;MM&gt;AMS, recumbent&gt;sitting).

Support
0568 Physiologic OSA Traits and CPAP Adherence Among Patients with Coronary Artery Disease and OSA
Authors: Zinchuk A , Yaggi H , Liang J , Chu J , Op De Beeck S , Stepnowski C , Wellman A , Peker Y , Sands S 
Published: May 2020

Abstract

Introduction
Obstructive sleep apnea (OSA) is common in patients with coronary artery disease (CAD), but adherence to continuous positive airway pressure (CPAP) in this population is poor. Low arousal threshold (ArTH), a pathophysiologic OSA trait, is associated with low rates of regular CPAP use in sleep clinic populations. We aimed to determine whether ArTH or other physiologic OSA traits (i.e. pharyngeal collapsibility, muscle compensation, loop gain) are associated with CPAP adherence in patients with CAD and OSA.

Methods
A secondary analysis of a randomized controlled trial of OSA treatment in patients with CAD (RICCADSA) was performed. OSA (apnea hypopnea index, AHI≥5/hour) was assessed by polysomnography. Arousal threshold (% eupneic ventilation, %Ve), loop gain (LG), pharyngeal collapsibility (%Ve) and compensation (%Ve) were estimated from polysomnography using a validated method. Adherence to auto-titrated CPAP (hours/night) was obtained from machine downloads at 1, 3, 6, 12 and 24 months. Mixed modelling was used to assess the association between OSA traits and CPAP adherence.

Results
Participants (n=262) were 64.1±7.9 years old, with BMI of 29.2±4.2 and 86% were men. The mean AHI was 40.8±23.6 events/hour with oxygen nadir of 81.3±7.1%. The median (IQR) CPAP adherence (hrs/night) was 3.0 (0.9, 5.8) at 1-mo and 3.0 (0.0, 5.6) at 24-mo. Compared to reference studies, the CAD patients exhibited an elevated LG 0.63 (0.53, 0.79), similar ArTH (%Ve) of 117.5% (106.5%, 136.4%), higher collapsibility (%Ve) at 90.1% (82.3%, 94.8%) and lower compensation (%Ve) at 3.7% (-0.7%, 8.7%).Only increasing pharyngeal muscle compensation was associated with lower CPAP adherence (β -0.04, p-value 0.048), effect modified by pharyngeal collapsibility (Compensation x Collapsibility, β &lt;0.01, p-value 0.042).

Conclusion
In this group of patients with CAD, increasing muscle compensation was associated with lower CPAP adherence. Physiologic OSA traits may provide insight into prediction of CPAP adherence among patients with OSA and CAD.

Support
Zinchuk: Parker B. Francis Fellowship Program in Clinical Research. Sands: American Heart Association. Peker: Swedish Research Council, Swedish Heart-Lung Foundation.