bluuebunny/crossref_metadata_2025_split huggingface dataset:
0600 Subjective reporting of Disrupted Nighttime Sleep and Associated Functional Outcomes in NT1 Youth
Authors: Heckler Gillian , Worhach Jennifer , Scammell Thomas , Maski Kiran 
Published: May 2023

Abstract

Introduction
In people with NT1, Disrupted Nighttime sleep (DNS) can be measured using the Wake/N1 Index, the number of transitions from sleep to wake or N1 sleep per hour of sleep. However, it remains unknown if this DNS measure correlates with sleep quality and daytime symptom burden. We compared the Wake/N1 Index with perceptions of sleep quality in young NT1 patients and healthy controls (HC) and determined its relationships with subjective sleep quality, daytime behavior, and cognition across groups.

Methods
25 HC (mean age 13.4 years) and 23 NT1 participants (mean age 15.8 years) completed a 15-item survey after sleeping a minimum of 6 hours during an in-lab polysomnogram. The survey included questions from validated surveys on habitual sleep quality, fatigue, sleepiness and cognitive function. We dichotomized survey responses into frequent or infrequent concerns. We compared responses using Fisher Exact tests and logistic regression to determine associations with the Wake/N1 Index. NT1 participants could take SSRI/SNRI medication for cataplexy but were weaned off wake-promoting medications and excluded if on an oxybate.

Results
Compared to HC, NT1 participants reported more frequent restless sleep, nighttime moaning/groaning/talking, tossing and turning, and waking more than once during the night (p’s &lt; 0.02) and showed a trend for more leg kicking during sleep (p=0.06). NT1 and HC groups did not differ in falling asleep quickly and returning back to sleep quickly after waking. NT1 subjects reported more frequent fatigue, difficulty keeping thoughts focused, difficulty thinking clearly and making decisions, problems remembering things, and dozing/napping inadvertently. Across groups and controlling for age, the Wake/N1 Index was associated with subjective reporting of waking more than once (OR=3.2) as well as problems with daytime alertness (OR 1.5) and fatigue (OR 1.4).

Conclusion
Young NT1 patients describe DNS as a multi-factorial complaint comprising problems with sleep maintenance, restless sleep, parasomnia-like behaviors, and periodic limb movements. The Wake/N1 Index is associated with perceptions of waking at night as well as daytime alertness and fatigue across groups. This work suggests that Wake/N1 Index could be a useful measure of sleep instability and inform future research on DNS impact on daytime function.

Support (if any)
NIH 5K23NS104267-2, Jazz Pharmaceuticals
0601 An Atypical Cause of Hallucinations in Type 1 Narcolepsy
Authors: Unger Jason , Arora Subodh , Creamer Jennifer , Hediger Lacie 
Published: May 2023

Abstract

Introduction
Narcolepsy is a disorder of hypersomnolence affecting between 1:5000-1:10,000 individuals. Type 1 Narcolepsy can be differentiated from Type 2 Narcolepsy by the presence of cataplexy. Visual hallucinations are reported in 50-80% of T1 Narcoleptics and ~25% of T2 Narcoleptics. This is thought to be a REM-related phenomenon occurring at transitions of sleep and wakefulness. Auditory hallucinations or paranoid delusions are more rare. We report a case of a 17 year old patient who experienced psychotic symptoms after trialing more than one class of stimulants.

Methods
This was primarily a retrospective case review. A subsequent literature search was performed reviewing similar reports of psychosis secondary to medications used to treat Narcolepsy.

Results
The patient is a 17 year old female who was 10 years old at the time of her diagnosis of Narcolepsy T1. At onset, the patient had reported cataplexy and visual hallucinations occurring at the time of sleep onset and wakening. After finding minimal help with stimulants, by age 15 she was maintained on sodium oxybate 6 grams per night for her cataplexy and started modafinil 200mg BID for wakefulness. She then reported new auditory hallucinations and hyperreligiosity and was admitted to inpatient psychiatry where both medications were discontinued. She was subsequently started on extended release methylphenidate and within 2 months had a recurrence of auditory hallucinations and hyperreligiosity resulting in two consecutive inpatient hospitalizations for psychosis.

Conclusion
Psychosis induced by medications for Narcolepsy has been reported in the literature where sodium oxybate and stimulants are the most common offending agents. Symptoms primarily related to modafinil or armodafinil are less frequently described. Most medications used to treat Narcolepsy may directly or indirectly act on dopamine pathways, which in theory have the propensity to lead to psychotic symptoms. Small studies of patients with Narcolepsy have reported psychosis in less than 1-2% of Modafinil users. Larger meta-analyses of patients with both Narcolepsy and Schizophrenia, have not found an increased likelihood for uncontrolled psychotic symptoms while on modafinil. Further case studies are needed to elucidate the relationship between stimulants and risk of psychosis in Narcolepsy patients.

Support (if any)
0602 Burden of Narcolepsy in Japan: A Nationwide Real-world Database Study from The Perspectives of Direct Medical Cost and Comorbidity
Authors: Kamada Yuta , Imanishi Aya , Chiu Shih-Wei , Yamaguchi Takuhiro 
Published: May 2023

Abstract

Introduction
In Japan, narcolepsy is not currently covered by a medical expense assistance program (e.g., System of Medical Payment for Services and Support for Persons with Disabilities). The people living with narcolepsy in Japan have been speaking up against current situation. However, to the best of our knowledge, reports about economic burden (direct + indirect) and comorbidity are limited in Japan. The study objectives were to reveal the burden of narcolepsy from the perspectives of direct medical cost and comorbidity, and also to compare it to epilepsy as a benchmark, which is covered by the above program.

Methods
Patients diagnosed with narcolepsy (&gt;1 ICD-10code [G47.4]) were identified from April 2017 to March 2022 using an employment-based health insurance claims data compiled by JMDC Inc. Patients with epilepsy (&gt;2 ICD-10code [G40]) were 1:4 matched for age, sex, insurance status, and observation period. Direct medical cost (including inpatient, outpatient, and medication) and comorbidity were analyzed. The 95% confidence intervals (CI) for differences of two diseases were calculated by bootstrapping (direct medical cost) or conditional logistic regression model (comorbidity). The protocol was approved by the Ethics Review Committee of the Tohoku University Graduate School of Medicine.

Results
We identified 4,594 patients with narcolepsy (sex; 58.7% males, age; 35.2 ± 12.7 years) and 18,376 patients with epilepsy (sex; 58.7% males, age; 35.8 ± 12.2 years). Overall annual direct medical cost per person was 349,188 JPY (narcolepsy) and 521,495 JPY (epilepsy). The difference was -172,307 JPY (95%CI; -199,793JPY to -146,567 JPY). Sleep apnea syndrome (odds ratio; 7.37, 95% CI; 6.52 to 8.33), ADHD (3.21, 2.86 to 3.61), and obesity (1.51, 1.22 to 1.87) were more prevalent in narcolepsy than in epilepsy, while developmental disorders (0.34, 0.27 to 0.41), fracture (0.78, 0.68 to 0.90), and high blood pressure (0.78, 0.71 to 0.86) were less prevalent.

Conclusion
This study showed direct medical cost and comorbidity of narcolepsy in Japan, which helps future discussion on the medical expense assistance program for people living with narcolepsy. Further research is needed to show the indirect economic burden to clarify the burden of narcolepsy.

Support (if any)
Eisai Co., Ltd.
0603 Characterization of Patients Who Had ≥5% Weight Loss With FT218 (Once-Nightly Sodium Oxybate): Post Hoc Analysis From REST-ON
Authors: Roth Thomas , Morse Anne , Bogan Richard , Roy Asim , Dubow Jordan , Gudeman Jennifer , Dauvilliers Yves 
Published: May 2023

Abstract

Introduction
Narcolepsy, particularly type 1 (NT1), is often comorbid with obesity. FT218 (LUMRYZ™) is an investigational once-nightly sodium oxybate (ON-SXB) formulation whose efficacy and safety were shown in the phase 3 REST-ON clinical trial (NCT02720744).

Methods
REST-ON was a 13-week, randomized (1:1), double-blind, placebo-controlled multicenter study in patients ≥16 years old with NT1/NT2. Stable concomitant stimulant use was permitted. A post hoc analysis of participants in the ON-SXB group experiencing ≥5% weight loss (weight-loss group) was conducted.

Results
In REST-ON (n=212), mean participant age was 31.2 years (range, 16–72), 67.9% were female, 75.5% were white, 76.4% had NT1, mean baseline BMI was 28.1 kg/m2 (range, 16.9–71.9), and 61.3% were taking stimulants. At week 13, 17.8% (19/107) of participants receiving ON-SXB experienced ≥5% weight loss vs 3.8% (4/105) of participants receiving placebo (P&lt; 0.001). Compared to the REST-ON population, the weight-loss group had similar age and proportion of NT1 diagnosis, a smaller proportion was female, and a higher proportion was white and was taking stimulants. At baseline, mean BMI was 25.6 kg/m2 (range, 20.3–34.0) in the weight-loss group, 47.4% (9/19) were overweight (BMI 25.0–29.9 kg/m2) or obese (BMI &gt;30 kg/m2); none were underweight (BMI &lt; 18.5 kg/m2). At week 13, 31.6% (6/19) remained overweight or obese; none were underweight. Excessive daytime sleepiness was significantly improved from baseline to week 13 (ON-SXB 9 g) in the weight-loss group vs the ON-SXB group without weight loss (Maintenance of Wakefulness test, P&lt; 0.05; Epworth Sleepiness Scale score, P&lt; 0.001). Adverse events of nausea and vomiting were more frequent in the weight-loss group vs the ON-SXB group without weight loss; however, rate of discontinuations owing to AEs in the weight-loss group was approximately half that of the ON-SXB group without weight loss.

Conclusion
These data expand the body of knowledge regarding weight loss during treatment with sodium oxybate. Given the high proportion of comorbid obesity among people with narcolepsy, the additional benefit of potential weight loss with sodium oxybate may further inform treatment selection. Whereas ON-SXB was effective overall, further exploration of possible increased pharmacologic response in certain subgroups should be evaluated.

Support (if any)
Avadel Pharmaceuticals
0607 Improvement in Sleep Latency With FT218 (Once-Nightly Sodium Oxybate): Analysis From the Phase 3 REST-ON Clinical Trial
Authors: Thorpy Michael , Shapiro Colin , Kushida Clete , Ohayon Maurice , Dubow Jordan , Gudeman Jennifer 
Published: May 2023

Abstract

Introduction
In the phase 3 REST-ON trial (NCT02720744), mean sleep latency on the Maintenance of Wakefulness Test (MWT) was significantly improved vs placebo with investigational, extended-release once-nightly sodium oxybate (FT218 [ON-SXB]; P&lt; 0.001). This post hoc analysis assessed response to treatment and improvement in excessive daytime sleepiness (EDS).

Methods
Participants (≥16 years) with narcolepsy type 1/2 were randomized 1:1 to double-blind ON-SXB or placebo. Doses were 4.5 g week 1, 6 g weeks 2‒3, 7.5 g weeks 4‒8, and 9 g weeks 9‒13. Mean sleep latency on the MWT was measured in 5 trials up to 30 minutes each at baseline and weeks 3, 8, and 13. Percentage of participants with improvement of ≥5, ≥10, ≥15, and ≥20 minutes from baseline and with mean sleep latency=30 minutes were assessed. Two-sided P values were calculated using Fisher exact test.

Results
The modified intent-to-treat population included 190 participants (ON-SXB, n=97; placebo, n=93). At baseline, mean (SD) sleep latency was as follows: ON-SXB, 5.0 (3.1) minutes; placebo, 4.7 (2.6) minutes. More participants receiving ON-SXB vs placebo had mean MWT=30 minutes at weeks 3 (6 g; 5.7% vs 0%; P&lt; 0.05), 8 (7.5 g; 10.5% vs 1.3%; P&lt; 0.05), and 13 (9 g; 13.2% vs 5.1%; P=0.14). A significantly greater percentage of participants receiving ON-SXB vs placebo had improved mean sleep latency ≥5 to ≥20 minutes over baseline at all doses (6 g: ≥5 min, 57.5% vs 25.0%; ≥10 min, 35.6% vs 9.1%; ≥15 min, 18.4% vs 3.4%; ≥20 min, 10.3% vs 1.1% [all P&lt; 0.01]; 7.5g: ≥5 min, 63.2% vs 28.2%; ≥10 min, 43.4% vs 11.5%; ≥15 min, 31.6% vs 3.8%; ≥20 min, 15.8% vs 1.3% [all P&lt; 0.001]; 9 g: ≥5 min, 66.2% vs 37.2% [P&lt; 0.001]; ≥10 min, 50.0% vs 19.2% [P&lt; 0.001]; ≥15 min, 32.4% vs 10.3% [P&lt; 0.01]; ≥20 min, 17.6% vs 6.4% [P&lt; 0.05]).

Conclusion
Clinically significant improvements in EDS occurred with 6-, 7.5-, and 9-g doses of ON-SXB. At the 2 highest doses, &gt;10% of participants remained awake for the entire MWT. If ON-SXB is granted FDA approval, adults with narcolepsy will have a once-nightly treatment to improve EDS.

Support (if any)
Avadel Pharmaceuticals
0612 Understanding Narcolepsy Treatments From the Patient’s Perspective: A Survey of People Living With Narcolepsy
Authors: Ortiz Luis , Morse Anne , Krahn Lois , Lavender Maggie , Horsnell Matthew , Cronin Dianna , Schneider Beth , Gudeman Jennifer 
Published: May 2023

Abstract

Introduction
Individuals with narcolepsy were surveyed to better understand desired treatment outcomes and how those outcomes map to commonly experienced symptoms, treatment awareness, and medication usage.

Methods
In February 2022, an email invitation to a 27-question online survey was sent to US members of MyNarcolepsyTeam, a social network of &gt;9,800 members.

Results
In total, 110 members completed the survey. The most frequently mentioned desired treatment goals aligned with the most commonly reported symptoms: being able to stop sleeping during the day (77%); increased energy (62%); improved memory (36%); improved productivity (29%); improved sleep continuity (22%); and for patients with narcolepsy type 1, reducing cataplexy (28%). A common theme was desire for a medication that would treat the underlying cause and not just improve specific symptoms. In one patient’s own words: “I want to see treatments that target the root problem of poor nighttime sleep rather than just being a band-aid for [excessive daytime sleepiness] EDS, like stimulants are.” Only a small percentage of respondents (13%) were not currently taking any type of medication to address narcolepsy symptoms. 64% were currently taking ≥2 medications to address both the daytime and nighttime symptoms. Most commonly mentioned current treatments were dextroamphetamine-amphetamine (30%), modafinil (22%), melatonin (16%), armodafinil (15%), venlafaxine (14%), and oxybate (14%). Notably, 33% of patients taking sodium oxybate chose sleeping through the night as a desired outcome. Most common sources for learning about treatments were narcolepsy-specific websites (53%), MyNarcolepsyTeam specifically (45%), the patient’s doctor (42%), scientific articles (42%), and advocacy groups (37%).

Conclusion
Patients experience a wide range of both daytime and nighttime symptoms and seek relief from both sets of symptoms including EDS (93%), fatigue (79%), cognitive challenges (74%), as well as sleep disruptions (63%). As a result, the majority need multiple medications. Understanding the experiences and needs of people with narcolepsy provides significant opportunities for clinicians to support, educate, and treat their patients holistically. Additionally, content readily available on the internet, whether it is narcolepsy-specific content or social networks, helps patients proactively discuss options with their clinician.

Support (if any)
Avadel Pharmaceuticals
0614 Characterizing Sleep in Early-Morning Shift Workers at Risk for Shift Work Disorder
Authors: Zitting Kirsi-Marja , Gilmore Katherine , Elkhadem Alexandria , Shaw Samantha , Deminico Marena , Lockyer Brandon , Quan Stuart , Wang Wei , Issa Nicolas , Williams Jonathan , Duffy Jeanne , Czeisler Charles 
Published: May 2023

Abstract

Introduction
Shift work is increasingly common in our 24/7 society and can cause sleep disturbances and excessive sleepiness. Roughly 10-43% of shift workers are diagnosed with shift work disorder (SWD), characterized by excessive sleepiness accompanied by reduced sleep duration and/or insomnia. While more individuals work early morning shifts (shift start 3-6AM) compared to overnight shifts, few studies have investigated this population. The aim of this study was to characterize sleep in a population of early-morning shift workers.

Methods
We characterized sleep in early-morning shift workers (18-65yrs) from New England who were screened for a clinical trial of a wake-promoting agent. Pre-screening consisted of the Epworth Sleepiness Scale (ESS) and a Shift Work Disorder Questionnaire (SWD); screening consisted of the Pittsburg Sleep Quality Index Questionnaire Questionnaire (PSQI) ; a physical exam including an ECG, CBC, urinalysis, and comprehensive metabolic panel; a home sleep test (HST), a Monitored Wakefulness Test (MWT); a physician evaluation of their excessive sleepiness (Clinical Global Impression [CGI]); and a self-evaluation regarding how sleepiness affected their everyday life (Patient Global Impression [PGI]). Only data from consented individuals who met the initial inclusion criteria of being high risk for SWD were included in the analysis.

Results
158 early-morning shift workers met the pre-screening criteria and began the screening process. Most worked in retail, healthcare, maintenance, or transportation, and worked five shifts (65%) and 40+ hours (72%) per week, with a duration of 8.8±1.9 hours. 41 were screened out for abnormal findings on the PE, ECG, or screening blood/urine tests; 26 were screened out for previously un-diagnosed OSA or PLMD; 4 were ineligible for other reasons; 7 were excluded after their MWT due to long sleep latency, 20 were lost to follow-up/withdrew and 60 completed screening and met inclusion criteria. Their average (±sd) age was 37±11 years, 45% women, PSQI score 7.5±2.7, sleep duration 5.6±1.0, ESS=16.3±3.1, CGI=4.2±0.9, PGI=3.6±1.1.

Conclusion
Early-morning shift workers at an increased risk for SWD report short and disturbed sleep, excessive sleepiness, and a negative impact of sleepiness on their quality of life. Many have undiagnosed OSA and PLMD.

Support (if any)
Axsome Therapeutics, Jazz Pharmaceuticals, Brigham and Women’s Hospital Center for Clinical Investigation.
0616 The rest-activity rhythm and its association with metabolic syndrome in midlife adults
Authors: Jeon Bomin , Moon Chooza 
Published: May 2023

Abstract

Introduction
Metabolic syndrome (MetS) in middle-aged adults increases a risk of cardiovascular disease in their older ages. The rest-activity rhythms disruptions have been linked to metabolic dysfunctions. However, there are limited data for the association between rest-activity rhythms and MetS in middle-aged. The purpose of this analysis was to compare rest-activity rhythms between midlife adults with MetS and those without MetS.

Methods
This study was a secondary analysis of data from Midlife in the United States (MIDUS 2): Biomarker Project, 2004-2009 cohort. The rest-activity rhythms were described by four parameters: the mesor, the amplitude, the acrophase, and the goodness-of-fit (R2), generated from Cosinor analysis using Actiwatch activity monitor data. Metabolic syndrome was defined as having three or more the following traits: the waist circumference ≥85cm in women and ≥102cm in men, the triglyceride level ≥150mg/dL, the high-density lipoprotein &lt; 50mg/dL in women and &lt; 40mg/dL in men, the blood pressure ≥130/85 mmHg, the fasting blood sugar level ≥100mg/dL. Student T-test were conducted.

Results
The sample (N=302; mean age 54.7 years [range 34 – 83]; 55.3% female; 97.3% White; 72.8) consists of 60.9% of persons with MetS (n=184) and 39.1% of those without MetS (n=118). The MetS group was older and more likely to be male than the non-MetS group (all p&lt;.05). The MetS group had statistically lower mesor (mean 221.7 vs. 246.1; p=.005) and amplitude (mean 183.1 vs. 207.9; p=.004) than the non-MetS group. R square (0.58 vs. 0.62; p=.004) was significantly lower in the MetS than the non-MetS group. However, acrophase was not associated with MetS.

Conclusion
Midlife adults, those with MetS had lower levels of average activity and lower amplitude of rest-activity rhythms than those with non-MetS. The circadian rest-activity rhythms were significantly fragmented in those with MetS than with those non-MetS. Our findings suggest that the disrupted rest-activity rhythm could be a modifiable factor to manage MetS in midlife.

Support (if any)
Partially supported by the University of Iowa Institute for Clinical and Translational Science (NIH/ ACTS KL2TR002536) and University of Iowa Center for Advancing Multimorbidity Science (NIH/ NINR P20 NR018081). Contents are solely the responsibility of the authors.
0617 Tracking circadian phase for personalized schedules: A precise medical approach to reduce circadian misalignment in shift workers
Authors: Neuenschwander Eva , Spector Tori , Kalmbach David , Sagong Chaewon , Drake Christopher , Cheng Philip 
Published: May 2023

Abstract

Introduction
Night shift workers experience symptoms of excessive sleepiness and insomnia due to misalignment between the work schedule and their circadian clock. Circadian misalignment can be corrected using exposure to bright light delivered in accordance with a phase response curve. Given the high variability of circadian phase in night shift workers, using a one-schedule-fits-all approach to light therapy might result in significant error (e.g., phase shifts in the wrong direction). Instead, a personalized light exposure schedule should result in more consistent and precise phase shifts. This randomized controlled trial compared personalized and non-personalized light schedules in shifting circadian phase in night shift workers.

Methods
Individuals with shift work disorder (ICSD-3 diagnostic criteria) were randomized into two conditions: personalized light therapy, or non-personalized light therapy control. Personalized light schedules were based on estimates of dim light melatonin onset (DLMO) derived from mathematical modeling of activity data collected via an Apple Watch. Estimates were confirmed with in-lab DLMO. Light schedules were delivered through a mobile app (SHIFT) that updated in accordance with real-time estimates of DLMO. Participants were provided a light box as a source of bright light at night and light blocking glasses. Phase shifts were determined based on in-lab DLMO measured before and after treatment.

Results
Those who received personalized light therapy treatment achieved a larger phase delay (Mean = 7.37 hours, SD = 3.03 hours) compared to those in the non-personalized light therapy control group (Mean = 0.84 hours, SD = 3.46 hours), t(5) = 2.501, p = 0.05.

Conclusion
Preliminary results suggest that personalized light therapy may be a more effective treatment to correct circadian misalignment in night shift workers by delivering treatment according to each individual’s unique circadian phase. This has implications for improving the symptoms of shift work disorder and quality of life for this population.

Support (if any)
Support for this study was provided from the National Institute of Health R41HL163783 and the American Academy of Sleep Medicine Foundation (245-SR-21) awarded to Dr. Philip Cheng.