bluuebunny/crossref_metadata_2025_split huggingface dataset:
0390 Efficacy of Lower-Sodium Oxybate in the Treatment of Idiopathic Hypersomnia: Evaluation of Response Based on the Idiopathic Hypersomnia Severity Scale Score
Authors: Dauvilliers Yves , Chen Abby , Steininger Teresa , Macfadden Wayne , Rosenberg Russell 
Published: May 2022

Abstract

Introduction
Idiopathic hypersomnia is a debilitating neurologic sleep disorder characterized by excessive daytime sleepiness (EDS), with sleep inertia and prolonged nighttime sleep as key symptoms in many patients. The Idiopathic Hypersomnia Severity Scale (IHSS) is a 14-item self-reported questionnaire (0–50 score range; higher scores indicate greater severity). The IHSS assesses key symptoms (EDS, sleep inertia, prolonged sleep). An IHSS total score ≤22 is considered normal; the established minimum clinically important difference (MCID) is 4 points. This post hoc analysis evaluated response to lower-sodium oxybate (LXB; Xywav®) treatment on IHSS scores in a phase 3 clinical trial (NCT03533114).

Methods
Eligible participants with idiopathic hypersomnia began LXB treatment with an open-label treatment titration and optimization period (OLT; 10–14 weeks), followed by a 2-week, open-label, stable-dose period (SDP). The IHSS was completed at baseline, during OLT (week [W]1, W4, W8, and end of OLT), and end of SDP. Response was defined as IHSS total score ≤22 or decrease in IHSS total score of ≥4 points after open-label LXB treatment.

Results
Participants were treatment naive (n=47) or taking alerting agents other than sodium oxybate at study entry (stable doses ≥2 months; n=62). At W1, W4, W8, end of OLT, and end of SDP, the percentage of participants achieving a response of total IHSS score ≤22 was 26.1%, 55.3%, 68.1%, 76.6%, and 80.9% (treatment-naive participants), respectively, and 24.2%, 53.2%, 60.7%, 71.0%, and 82.3% (participants taking alerting agents), respectively. At W1, W4, W8, end of OLT, and end of SDP, the percentage of participants achieving a response of total IHSS score decrease of ≥4 points was 45.7%, 80.9%, 83.0%, 97.9%, and 93.6% (treatment-naive participants), respectively, and 46.8%, 79.0%, 83.6%, 90.3%, and 98.4% (participants taking alerting agents), respectively. Treatment-emergent adverse events (≥10%) included nausea, headache, dizziness, anxiety, and vomiting.

Conclusion
Over 80% of participants achieved a clinically meaningful response based upon IHSS total score ≤22, and up to 98% demonstrated a decrease in total IHSS score of ≥4 points at end of SDP. The response rate defined by either parameter increased over the study period. The safety profile of LXB was consistent with that observed in narcolepsy.

Support (If Any)
Jazz Pharmaceuticals.
0396 Characteristics and Disease Burden of Patients With Idiopathic Hypersomnia With and Without Long Sleep Time: The Real-World Idiopathic Hypersomnia Outcomes Study (ARISE)
Authors: Schneider Logan , Stevens Joanne , Husain Aatif , Ito Diane , Fuller Douglas , Macfadden Wayne 
Published: May 2022

Abstract

Introduction
Idiopathic hypersomnia is a debilitating central disorder of hypersomnolence. The Real World Idiopathic Hypersomnia Outcomes Study (ARISE) assessed the symptoms and impact of idiopathic hypersomnia.

Methods
US-based adults with idiopathic hypersomnia with or without long sleep time (LST; ≥11 hours of sleep in a 24-hour period [self-reported]) completed an online survey assessing symptom severity (Epworth Sleepiness Scale [ESS]; Idiopathic Hypersomnia Severity Scale [IHSS]), daily functioning (Functional Outcomes of Sleep Questionnaire [FOSQ-10]), quality of life (Neuro-QoL), cognition (British Columbia Cognitive Complaints Inventory [BC-CCI]), depression (Patient Health Questionnaire-9 [PHQ-9]), work/activity impairment (Work Productivity and Activity Impairment Questionnaire: Specific Health Problem v2.0 [WPAI:SHP]), and treatment satisfaction (Treatment Satisfaction Questionnaire for Medication vII [TSQM]).

Results
Of 75 participants enrolled, 37 were with LST and 38 were without long sleep (non-LST). Most were female (LST, 73.0%; non-LST, 89.5%) and took medication for idiopathic hypersomnia (LST, 97.3%; non-LST, 81.6%); mean age was 33.7 years (LST) and 34.4 years (non-LST). In LST and non-LST participants, respectively, mean (SD) ESS scores were 15.4 (3.8) and 13.6 (3.0), mean (SD) IHSS scores were 38.2 (7.1) and 32.2 (7.0), and mean (SD) FOSQ-10 scores were 9.6 (2.3) and 11.9 (2.8); mean (SD) Neuro-QoL scores were 22.9 (6.1) and 26.8 (5.7) for ability to participate in social roles/activities and 22.5 (6.6) and 17.4 (5.0) for stigma. Severe cognitive complaints (BC-CCI score 15–18) were reported by 35.1% and 18.4% of LST and non-LST participants, respectively, and severe depression (PHQ-9 score ≥20) was reported by 13.5% and 5.3%. Mean (SD) WPAI:SHP scores in LST and non-LST participants were 57.1 (21.9) and 41.5 (21.4) for presenteeism, 60.1 (24.1) and 45.8 (23.8) for absenteeism+presenteeism, and 72.2 (17.3) and 56.1 (23.2) for activity impairment. Mean (SD) TSQM scores in LST and non-LST participants were 57.9 (21.4) and 66.7 (20.3) for global satisfaction and 49.1 (16.6) and 56.2 (19.7) for effectiveness.

Conclusion
People with idiopathic hypersomnia with long sleep time report greater sleepiness; poorer quality of life, cognition, daily functioning, and work performance; a higher rate of severe depression; and less satisfaction with treatment, compared with those without long sleep time.

Support (If Any)
Jazz Pharmaceuticals.
0401 Efficacy of Once-Nightly Sodium Oxybate (ON-SXB; FT218) By Narcolepsy Type: Post-hoc Analyses From the REST-ON Trial
Authors: Dauvilliers Yves , Roth Thomas , Bogan Richard , Thorpy Michael , Morse Anne Marie , Roy Asim , Seiden David , Dubow Jordan , Gudeman Jennifer 
Published: May 2022

Abstract

Introduction
Once-nightly sodium oxybate (ON-SXB; FT218) was evaluated for treatment of narcolepsy in the phase 3 REST-ON trial (NCT02720744). Significant improvement was shown for the three coprimary endpoints mean sleep latency on the Maintenance of Wakefulness test (MWT), Clinical Global Impression of Improvement (CGI-I) rating, and weekly number of cataplexy attacks overall (all P&lt;0.001 vs placebo) and in post-hoc analyses by narcolepsy type (NT1/NT2) for MWT and CGI-I (all P&lt;0.05). Post-hoc efficacy analyses of objective and subjective measures of disrupted nighttime sleep and daytime sleepiness by narcolepsy type were conducted.

Methods
Participants aged ≥16 years were randomized 1:1 to receive ON-SXB (1 week, 4.5 g; 2 weeks, 6 g; 5 weeks, 7.5 g; 5 weeks, 9 g) or placebo. Mixed-effects models for repeated measures were used to calculate P values for change from baseline vs placebo at weeks 3 (6 g), 8 (7.5 g), and 13 (9 g) for secondary REST-ON endpoints of Epworth sleepiness scale (ESS) score, sleep shifts (ie, the number of shifts from stages N1, N2, N3 and rapid eye movement [REM] sleep to Wake and from N2, N3 and REM sleep to N1), nocturnal arousals (NA), and patient-reported sleep quality and refreshing nature of sleep (100-point visual analog scale).

Results
Of 190 participants, 145 had NT1 (ON-SXB, n=73; placebo, n=72) and 45 had NT2 (ON-SXB, n=24; placebo, n=21). Improvements with ON-SXB vs placebo were reported for shifts to a lighter stage of sleep (NT1: 6, 7.5, 9 g, all P&lt;0.001; NT2: 6 and 7.5 g, P&lt;0.05; 9 g, P&lt;0.001), NA (NT1: 6 g, P&lt;0.05; 7.5 and 9 g, P&lt;0.01; NT2: 6 g, directional improvement; 7.5 and 9 g, P&lt;0.05), and sleep quality (NT1: 6, 7.5, 9 g, all P&lt;0.001; NT2: 6, 7.5, 9 g, all P&lt;0.05). Significant improvements in ESS and refreshing nature of sleep for ON-SXB vs placebo were reported for NT1 (6, 7.5, 9 g, P≤0.001) with directional improvements observed for the NT2 subgroup.

Conclusion
Results of these subgroup efficacy analyses are generally consistent with previously reported REST-ON endpoints and support ON-SXB treatment efficacy in adults with NT1 or NT2.

Support (If Any)
Avadel Pharmaceuticals
0410 Utility of the Urine Drug Screen in Maintenance of Wakefulness Testing Interpretation - A Single-Center, Retrospective Analysis in Pediatric Patients
Authors: Witt Rochelle , Wisniewski Benjamin , Cole Melissa , Gurbani Neepa , Huang Guixia , Hossain Md Monir , Simakajornboon Narong 
Published: May 2022

Abstract

Introduction
Accurate assessment of hypersomnia depends upon consideration of several factors, including use of medications that affect alertness and sleep organization. Urine drug screens (UDS) are recommended when assessing hypersomnia, but there is little standardization with respect to screening methods, types of substances detected, and use in maintenance of wakefulness test (MWT) interpretation, in part because there is scant literature relating UDS results to patients’ characteristics, MWT findings and implications.

Methods
A retrospective analysis was performed in adolescents evaluated at Cincinnati Children's Sleep Center between 2008 and 2021 who underwent MWT with concurrent UDS to determine the adequacy of hypersomnia treatment. UDS in our laboratory were performed by Qualitative Immunoassay/Gas Chromatography-Mass Spectrometry/Liquid Chromatography-Tandem Mass Spectrometry.

Results
A total of 109 MWTs were accompanied by UDS in 79 patients. Patients were 17.7 [16.6, 18.6] years old (median, [IQ range]), 41.3% female, 68.8% White, 25.7% Black, 5.5% Other, with a BMI of 25.8 [22.1, 31.8] kg/m2. 85.3% had narcolepsy. In addition to prescribed medications, caffeine was positive in 54.1% of UDS, and diphenhydramine was positive in 58.7%. No patients reported use of caffeine or diphenhydramine on the day of MWT. There were no significant demographic differences between those who tested positive and negative for caffeine. The median sleep latency in those with caffeine-positive UDS was longer than those with caffeine-negative UDS, although it did not reach statistical significance (27.3 [14.7, 38.3] vs 19.1 [9.8, 36.1] minutes; P=0.15). Patients with a positive UDS for diphenhydramine all took modafinil/armodafinil. In addition, 80% of patients taking modafinil/armodafinil had diphenhydramine-positive results. Nicotine and cannabinoids were detected in 2 UDS.

Conclusion
Two unexpected substances (caffeine and diphenhydramine) were found on UDS during MWTs in a significant proportion of our cohort. Caffeine may influence the results of MWTs, although further investigations are warranted. The unexpected presence of diphenhydramine is a false positive for those patients on modafinil/armodafinil (supported by literature and confirmed by our laboratory director). Sleep clinicians should be aware of these findings and the implications of unexpected substances when interpreting MWTs.

Support (If Any)
Cincinnati Children's Hospital Research Fund
0419 Characterization of Sleep Quality in Patients with Idiopathic Hypersomnia using Cardiopulmonary Coupling
Authors: Pawar Rahul , Hilmisson Hugi , Crawford Bredon , Thomas Robert , Blattner Margaret 
Published: May 2022

Abstract

Introduction
Idiopathic Hypersomnia (IH) is characterized clinically by excessive daytime sleepiness, prolonged or unrefreshing sleep, and sleep inertia. The ICSD-3 classifies IH as having expected proportions of NREM and REM sleep, normal REM latency and relatively high sleep efficiency. However, there is limited granular data on sleep quality in these patients and whether this disease state comprises of patients with a homogenous spectrum of sleep quality. The aim of this study is to describe the sleep quality in patients with IH using the ECG derived sleep spectrogram.

Methods
This is a single center cross sectional study where we identified 37 consecutive extended sleep studies for patients with 10 or more hours of total sleep time (TST). The sleep spectrogram is an ECG or plethysmography based system which evaluates sleep stability based on the principle of autonomic and respiratory oscillations (cardiopulmonary coupling). High frequency coupling (HFC) is associated with stable NREM sleep. Sleep quality index (SQI) is strongly weighted by HFC. We a priori decided to divide this population into 2 groups based on SQI ≥55 (there is published supportive data for using this threshold in adults) and compare them using T-test. Multivariable logistic regression was performed adjusting for age, sex, TST and apnea-hypopnea index-3% (AHI) &lt;10 to assess predictors of high or low SQI which was discovered.

Results
The mean age for the cohort was 35.4 years (SD 16.2), of which 30 (81%) were females. Mean TST was 660 minutes (SD 16.2) with mean sleep efficiency of 86% (SD 9) and mean SQI of 59% (SD 19.1). Mean AHI was 10.4 (SD 12.3). Stratifying the cohort based on SQI gave us 2 distinct groups with mean SQI of 71.5 (SD 9.3) in group with SQI≥55 and mean SQI of 38.5 (SD 11.6) in group with SQI &lt;55 [p-value &lt;0.001]. In a logistic regression analysis, the SQI was not predicted by AHI &lt;10, age, gender or total sleep time.

Conclusion
Based on our cohort, at least two clusters were identified in IH. We anticipate that the findings here will lead to further insights in IH physiology and phenotypes.

Support (If Any)
0420 Characterization of Brain Age in Patients with Prolonged Sleep Duration
Authors: Crawford Bredon , Pawar Rahul , Sun Haoqi , Westover Michael , Thomas Robert , Blattner Margaret 
Published: May 2022

Abstract

Introduction
We identified 35 consecutive extended sleep studies for patients with 10 or more hours of total sleep time, and applied the BAI model to these studies. The BAI model was trained using sleep studies from relatively healthy participants. The sleep EEG features were extracted from both the spectral domain and the waveform. For each sleep stage, we extracted 96 features, and each of the features was averaged across the sleep stages. The resulting features were concatenated to form 480 features to represent the entire recording of sleep. These features are fed into a linear regression model and then adjusted to reduce age-dependent bias.

Methods
We identified 35 consecutive extended sleep studies for patients with 10 or more hours of total sleep time, and applied the BAI model to these studies. The BAI model was trained using sleep studies from relatively healthy participants. The sleep EEG features were extracted from both the spectral domain and the waveform. For each sleep stage, we extracted 96 features, and each of the features was averaged across the sleep stages. The resulting features were concatenated to form 480 features to represent the entire recording of sleep. These features are fed into a linear regression model and then adjusted to reduce age-dependent bias

Results
35 extended polysomnograms were reviewed for patients undergoing evaluation for hypersomnia, with a median age of 27 years (range 16-76), and female predominance (28/35, 80%). This hypersomnia cohort forms two clusters by Gaussian mixture modeling. Patients in the first cluster exhibit a brain age that correlates well to chronological age (mean BAI = 4.4yr), while patients in the second cluster exhibit a brain age 12.4 years younger than chronological age (mean BAI = -12.4yr). The EEG spectrogram in the low BAI cluster shows high spindle band power, high delta band power, and high peak frequency of posterior dominant rhythm when compared to their age norms.

Conclusion
A subset of hypersomnia patients demonstrates a combination of EEG features associated with lower chronological age. We anticipate that the findings here will lead to further insights in IH physiology and phenotypes.

Support (If Any)
NIH R01NS102190, R01NS102574, R01NS107291, RF1AG064312, R01AG062989, R01AG073410
0438 The Impact of Unit Cohesion on Insomnia Symptoms among Army Soldiers
Authors: Barilla Holly , Gehrman Philip , Brownlow Janeese , Klingaman Elizabeth , Miller Katherine 
Published: May 2022

Abstract

Introduction
Sleep disturbance is common in military personnel and is often related to stressful conditions and deployment to a warzone. Among soldiers, the achievement of unit goals and performance is often dependent upon how cohesive members of the unit are. The quality of unit experiences in terms of reliance on other unit members, feeling respected, and interpersonal relationships could impact the ability to sleep at night. The primary hypothesis of this analysis was that poorer quality unit experiences would be associated with worse sleep at night.

Methods
Data were acquired from the All Army Study of the Army Study to Assess Risk and Resilience in Service members (STARRS; N= 21,449; 28.65 {SD=7.45} years old; 88.24% male). Participants completed the Brief Insomnia Questionnaire, and current insomnia status was determined by DSM-5 criteria. They also completed survey items related to how much respect they had for their officers and other members of their unit as well as how much respect they received in return, their overall morale and if they felt they could rely on members of their unit. T-tests and Chi-square tests were used to examine the associations between insomnia and unit experiences.

Results
More negative feelings about unit cohesiveness was associated with higher rates of insomnia (t(19401)= -41.19, p&lt;.0001). Similarly, greater feelings of not being respected by other unit members was associated with higher rates of insomnia (X2 (3, N=19275) = 869.9, p&lt;.0001). Strongly believing that the job reward was not worth the effort that was put into their work also had a significant increase in disturbed sleep (X2 (4, N=19214) = 1120.5, p&lt;.0001).

Conclusion
These results demonstrate that, among Army soldiers, poorer quality experiences with other unit members are related to higher rates of insomnia symptoms. Service members who felt they could not rely on other members of their unit, did not feel their officers respected them, and could not speak openly to officers endorsed strong feelings regarding how cohesive their unit was and ultimately reported poorer sleep.

Support (If Any)
This publication is based on public use data from Army STARRS (Inter-university Consortium for Political and Social Research, University of Michigan-http://doi.org/10.3886/ICPSR35197-v1), funded by U.S. NIMH-U01MH087981. KEM’s time was supported by the U.S Department of Veterans Affairs, Veterans Health Administration (Clinical Science Research and Development Service – IK2 CX001874). EAK’s time was supported by the U.S Department of Veterans Affairs, Rehabilitation Research and Development Service – 1IK2 RX001836.
0442 Improved resilience following Cognitive Behavioral Therapy for Insomnia mediates treatment outcomes and protects against long-term insomnia and depression
Authors: Cheng Philip , Kalmbach David , Hsieh Hsing-Fang , Castelan Andrea Cuamatzi , Sagong Chaewon , Drake Christopher 
Published: May 2022

Abstract

Introduction
While the negative consequences of insomnia are well-documented, a strengths-based understanding of how sleep can promote health promotion is still emerging and much-needed. Correlational evidence has connected sleep and insomnia to resilience; however, this relationship has not yet been experimentally tested. This study examined resilience as mediator of treatment outcomes in a randomized clinical trial with insomnia patients.

Methods
Participants were randomized to either digital Cognitive Behavioral Therapy for insomnia (dCBT-I; n=358) or sleep education control (n=300), and assessed at pre-treatment, post-treatment, and one-year follow-up. A structural equation modeling framework was utilized to test resilience as a mediator of insomnia and depression. Risk for insomnia and depression was also tested in the model, operationalized as a latent factor with sleep reactivity, stress, and rumination as indicators (aligned with the 3-P model). Sensitivity analyses tested the impact of change in resilience on the insomnia relapse and incident depression at one-year follow-up.

Results
dCBT-I resulted in greater improvements in resilience compared to the sleep education control. The improved resilience was a significant mediator of reduced insomnia and depression severity following treatment. Furthermore, improved resilience following dCBT-I also reduced insomnia and depression at one-year follow-up by lowering latent risk. Sensitivity analyses indicated that each point improvement in resilience following treatment reduced the odds of insomnia relapse and incident depression one year later by 76% and 65% respectively.

Conclusion
Improved resilience is a contributing mechanism to treatment gains following dCBT-I and may further protect against longer-term insomnia and depression by reducing risk.

Support (If Any)
K23HL138166; R01HL159180
0444 The effect of distinct components of CBT-I on slow wave power and energy
Authors: Ahmadi Maryam , Krause Adam , O’Hora Kathleen , Hernandez Beatriz , Lazzeroni Laura , Zeitzer Jamie , Friedman Leah , Posner Donn , Kushida Clete Kushida clete@stanford edu , Yesavage Jerome , Saletin Jared , Goldstein-Piekarski Andrea 
Published: May 2022

Abstract

Introduction
Cognitive-behavioral therapy for insomnia (CBT-I) is an effective multi-component treatment known to improve sleep in older adults with insomnia, including increasing NREM slow-wave activity (SWA) EEG power (0.5 – 4.75Hz) and sleep depth. However, the relative contributions of distinct components of CBT-I to changes in SWA remain unknown.

Methods
We examined the relative impact of specific components of CBT-I: behavioral therapy (sleep restriction + stimulus control) (BT), cognitive therapy (CT), and combined BT and CT (CBT) on SWA in 111 older adults (75 female; mean age: 69±6.1 years) with insomnia (Insomnia Severity Index &gt;10). Participants underwent polysomnography (PSG) at baseline prior to being randomized to a 6-session treatment regimen of BT, CT, or CBT. PSG was reassessed immediately following treatment and at 6-months follow-up. We computed SWA and time-accumulated slow-wave energy (SWE) at each time point. Mixed-effects models compared treatment efficacy on SWA and SWE outcomes.

Results
We identified significant time-by-treatment interactions for both SWA (B=0.69, t=2.14, p=0.034) and SWE (B=0.93, t=1.98, p=0.049). Post-hoc tests revealed that SWA/SWE increased from baseline to the end of treatment for CT group (SWA: d=0.42, SWE: d=0.54), while there were limited changes in the BT (SWA: d=0.27, SWE: d=0.29) and in the CBT groups (SWA: d=0.18, SWE: d=0.06). These changes were absent at 6-month follow up.

Conclusion
Our preliminary results indicated that different components of CBT-I have distinct effects on SWA/SWE with CT alone indicating improved NREM sleep quality. Given previous findings of lower SWA for sleep misperceptors underestimating their sleep depth, compared with good-sleepers, this result may suggest that reducing misperception of sleep with CT increases SWA/SWE. Further study is needed to dissociate the effect of BT from CT in combined CBT-I.

Support (If Any)