bluuebunny/crossref_metadata_2025 huggingface dataset:
0293 The Effect of Sleep Loss on Divergent Thinking using a Remote Associates Task
Authors: Vignali Jonathan , Carlsson Kajsa , Doty Tracy Jill , Thomas Balkin , Burke Tina
Published: May 2022

Introduction

Sleep loss-induced neurobehavioral deficits are a recognized threat to health, safety, and performance. Sleep loss has previously been shown to differentially impact distinct types of cognitive function, although less is known about the higher-order cognitive function, divergent thinking. Understanding the influence of sleep on divergent thinking can assist in developing targeted strategies to mitigate specific cognitive function impairments.

Methods

Eight participants (3M/5F), mean age 27.875y (± 5.5y SD) were studied over the course of 40 days in a crossover design. Participants were randomly assigned to one of two study schedules, with 4 participants in each that alternated the order of sleep restriction and total sleep deprivation. The schedules consisted of a baseline assessment and 6 study phases [sleep extension prior to sleep restriction (10h Time in Bed (TIB)), sleep restriction (6h TIB), recovery following sleep restriction, sleep extension prior to total sleep deprivation (10h TIB), total sleep deprivation (62h), and recovery following sleep restriction. The Remote Associates Task (RAT), a task to assess divergent thinking by presenting a triad of apparently unrelated words with the goal of identifying a unifying 4th word, was administered the evening of the last day of every phase. RAT performance metrics included number of triads attempted, correct responses, repeated trials, and mean correct and incorrect reaction times.

Results

No differences were found in total number of word triads attempted by participants (p=0.18). The number of correct responses during baseline was lower than during sleep restriction, recovery from sleep restriction, and total sleep restriction (p=0.00691), most likely reflecting a steep learning curve. No significant main effect of phase was found for any RAT metric.

Conclusion

These preliminary findings suggest divergent thought as measured by the RAT is conserved across a differential amounts of sleep. More studies are needed to better characterize the impact of sleep loss on divergent thinking as well as possible mediating effects of other higher-order cognitive functions.

Support (If Any)

Department of Defense Military Operational Medicine Research Program (MOMRP)
0298 Kynurenic Acid Synthesis Inhibitor Promotes Enhanced Sleep Recovery Following Acute Sleep Deprivation in Adult Wistar Rats
Authors: Wright Courtney , Milosavljevic Snezana , Pocivavsek Ana
Published: May 2022

Introduction

Sleep disorders and cognitive dysfunction often afflict the general population and are common amongst patients with neuropsychiatric disorders like schizophrenia. Sleep deprivation (SD) disrupts cognitive function, yet little is known about underlying mechanisms. The tryptophan metabolite kynurenic acid (KYNA), an endogenous a7nACh and NMDA receptor antagonist, is synthesized by kynurenine aminotransferase II (KAT II). KYNA is increased in the brain of patients with schizophrenia and our translational studies demonstrate that elevated KYNA disrupts hippocampal learning and sleep architecture in rodents (Pocivavsek et al. 2017 Sleep). We hypothesize a mechanistic link between KYNA, sleep, and cognitive dysfunction.

Methods

In vivo microdialysis in the dorsal hippocampus and simultaneous EEG/EMG telemetry was conducted in adult male Wistar rats (N=3-5 per group). Using a within-subjects experimental design, rats underwent a control and SD day. Animals received either vehicle or KAT II inhibitor PF-04859989 (PF), 30mg/kg s.c., on both days at zeitgeber time (ZT) 0 or ZT6. SD occurred from ZT0-6 by gentle handling. KYNA levels were evaluated in the microdialysate.

Results

SD effectively eliminated REM sleep (100%) and significantly reduced NREM (94%) during ZT0-6. Extracellular KYNA levels in the hippocampus significantly increased with SD (2-way ANOVA, time x SD: **P<0.0001) and PF readily prevented this accumulation. Initial sleep recovery (ZT6-12) did not significantly differ between treatment groups. During the dark phase (ZT12-24), PF treatment of SD animals promoted REM sleep parameters, including total REM duration (2-way ANOVA, SD x treatment ZT: P<0.05). PF treatment enhanced theta spectral power determined by Discrete Fourier transform during REM sleep recovery (ZT12-24). PF alone during the control day enhanced NREM delta power (P<0.05) during the late light phase (ZT6-12).

Conclusion

Importantly, the KAT II inhibitor PF promoted sleep recovery following acute SD, supporting our hypothesis that the accumulation of KYNA may exacerbate sleep disruptions. Changes in sleep parameters elicited by PF, a potential therapeutic avenue, may be indicative of mild somnolence. The present and future complementary experiments with cognitive behavioral tasks in rodents support our understanding of the role of KYNA in modulating sleep and cognition.

Support (If Any)

National Institutes of Health Grant No. NIH R01 NS102209
0304 Characterizing age and sex-related changes in sleep EEG K-complex morphology in 3,909 individuals
Authors: Valencia Daphne , Schoenholz Reagan , Bischoff Giles , Mullins Anna , Kam Korey , Fakhoury Ahmad , Varga Andrew , Rapoport David , Ayappa Indu , Mazumdar Madhu , Berkalieva Asem , Parekh Ankit
Published: May 2022

Introduction

K-complexes are hallmarks of sleep stage N2 and are thought to be associated with two distinct roles that serve as either or both, a sleep protective mechanism or a cortical arousal response. K-complexes and their morphological features (number, delta surrounding K complexes, etc.) have been implicated in sustained attention as well as in Alzheimer’s disease wherein a decline in the number of K-complexes appeared to discriminate diseased individuals from healthy controls. Yet, age and sex-related changes in K-complex morphology are not well-known.

Methods

We analyzed data from the Sleep Heart Health Study (SHHS) to understand age- and sex-related changes in K-complex morphology. The SHHS is a cohort study comprised of 5,804 men and women aged 40 and older aimed at investigating the cardiovascular consequences of sleep-disordered breathing. K-complex (on C3/A2) features were quantified using previously published and validated open-source algorithm (DETOKS; Parekh et. al. J. Neurosci Meth. 2015). Three features of K-complexes were studied: number of K-complexes (density), delta (∆SWAK) and alpha (∆alphaK) surrounding K-complexes.

Results

Of the 5,804 studies available, 3,909 that had at least 6h of usable EEG were analyzed (mean = 62±11 yrs., range [40-90 yrs.], 53%female). With aging, K-complex density and (rho=-0.1, p<0.0001), ∆SWAK (rho=-0.2, p<0.0001) were inversely associated with age, while ∆alphaK (rho=0.1, p<0.01) was significantly positively associated with age. The inverse association of K-complex density with age was greater in men compared to women (rhomen=-0.3, p<0.0001, rhowomen=-0.1, p<0.01). Women had greater K-complex density compared to men (1.8[1.3-2.4] vs. 1.3[0.9-1.8], median[IQR]; std. mean diff =0.4). The changes in K-complex morphology with age remained significant after controlling for OSA severity.

Conclusion

Age is associated with decline in K-complex morphology such that K-complex density and delta activity surrounding K-complexes declines whereas alpha activity surrounding K-complexes increases. An age-related decline in delta activity surrounding K-complexes and an increase in alpha activity surrounding K-complexes is consistent with the potential role for these features in either sleep-state maintenance or arousal responsiveness. Whether the decline in K-complex morphology seen here with aging, and its interaction with sex-related differences, is accelerated in neurodegenerative disorders such as AD remains to be tested.

Support (If Any)

Support: NIH K25HL151912, AASMFoundation BS-233-20
0313 The Role of Objective Sleep on Subjective and Objective Cognition in Older Adults with Insomnia: A Pilot Study
Authors: Costa Amy , Musich Madison , Knous Dakota , McCrae Christina , Cowan Nelson , Curtis Ashley
Published: May 2022

Introduction

Cognitive complaints and objective cognitive dysfunction are common in aging populations, but findings regarding associations between them are inconclusive. Given age-related sleep changes [more lighter-staged sleep, reduced sleep efficiency (SE)], and known relationships between insomnia complaints and cognitive dysfunction, this pilot tested whether polysomnographic sleep moderates associations between subjective and objective cognition in older adults with insomnia complaints.

Methods

Older adults with insomnia complaints (N=37, Mage=68.9, SD=6.23, 20 women) completed one night of polysomnography (Sleep Profiler-PSG2TM) and the NIH Toolbox [Pattern Comparison (processing speed), Dimensional Change Card Sort (cognitive flexibility), Stroop (attention and inhibition), and Sternberg (working memory). Additionally, participants completed the Cognitive Failures Questionnaire (subscores CFQ-memory, CFQ-distractibility CFQ-blunders computed). Multiple regressions examined if polysomnographic sleep (SE, %N1, %N3) moderated associations between subjective/objective cognition, controlling for apnea-hypopnea index and depression.

Results

%N1 moderated associations between Sternberg performance and CFQ-memory (R2=.13, p=.03), CFQ-distractibility (R2=.20 p=.01) and CFQ-blunders (R2=.19 p=.02). At highest %N1, worse working memory was associated with less complaints in memory (β=16.4, p=.03), distractibility (β=12.4, p=.009) and blunders (β=15.3, p=.02). Additionally, %N1 (R2=.14, p=.02) and SE (R2=.17, p=.02) moderated the association between dimensional change performance and CFQ-distractibility. At lowest %N1, worse cognitive flexibility was associated with more distractibility complaints (β=-988.8, p=.02), while at highest %N1, worse cognitive flexibility was associated with less distractibility complaints (β=3881.4, p=.02). At lowest SE, worse cognitive flexibility was associated with less distractibility complaints (β=2354.0 p=.02), while at highest SE, worse cognitive flexibility was associated with more distractibility complaints (β=-1414.1 p=.03).

Conclusion

Preliminary findings suggest in older adults with insomnia complaints, greater time spent in lighter-staged sleep and more sleep fragmentation may exacerbate discrepancies in the objective/subjective cognition relationship, while less time spent in lighter-staged sleep and less sleep fragmentation may converge the objective/subjective relationship. Objective sleep should be considered when understanding discrepancies between subjective reports versus neuropsychological/objective cognition profiles. Prospective studies with larger samples examining how sleep impacts the trajectory of subjective/objective cognition in aging are warranted.

Support (If Any)

This research was made possible by an award (PI:Curtis) from the American Academy of Sleep Medicine Foundation, a foundation of the American Academy of Sleep Medicine.
0326 Influence of Sleep and Cardiovascular Health on Cognitive Outcomes in Older Adults
Authors: Maybrier Hannah , Lucey Brendan , Holtzman David , Head Denise
Published: May 2022

Introduction

High and low sleep duration have been associated with reduced executive function (EF) and episodic memory (EM). However, causal pathways have not been identified. Cardiovascular health may contribute to the relationship between sleep and cognitive aging. Sleep disturbance has been associated with increased hypertension and heart disease in older adults, and cerebrovascular insufficiency has been consistently linked with cognitive decline. Therefore, the mediating and moderating effects of cardiovascular disease risk (CVD) on the relationship between sleep duration and longitudinal change in EF and EM were examined.

Methods

Statistical analyses were preregistered (osf.io/6yw7g). Average total sleep time (TST) over 2-6 nights was estimated using single-channel EEG at baseline (N=332). CVD was estimated using the abbreviated Framingham Heart Score approximately one year post-baseline. Outcome variables were linear change in EF and EM composite scores [BL1] per year up to 7 years after baseline. EF subtests measured semantic fluency, working memory, and task switching. EM subtests measured verbal associative memory, narrative episodic memory, and list learning. Covariates included age, gender, Alzheimer disease (AD) biomarkers (ratio of phosphorylated tau181 to amyloid-ß42), global cognition, and apnea-hypopnea index.

Results

Greater TST was linearly associated with reduced CVD (ß=-.157, p=.006). Quadratic effects of TST on EF and EM were observed (EF: ß=-.105, p=.002; EM: ß=-.203, p=.007). Lowest TST was related to greater reduction in EF; highest TST was related to greater reduction in EF and EM. Mediating effects of CVD for EF and EM were observed (ps<.05) but were non-significant when age and AD biomarkers were included (p=.10, p=.08, respectively). A non-significant trend indicated CVD moderated effects of TST on EF (ß=.10, p=.055), controlling for age and AD biomarkers. Less sleep combined with higher CVD tended to be associated with greater decline in EF. CVD did not moderate effects of TST on EM (ß=.07, p=.254).

Conclusion

Consistent with prior literature, CVD and TST were independently associated with cognitive decline. Although findings suggest that CVD may influence effects of TST on cognitive decline, more evidence is needed. Future analyses will examine alternative sleep measures (e.g., sleep efficiency, slow wave spectral density).

Support (If Any)

NIH: T32-AG000030, P01-AG03991, P01-AG026276, P30-AG066444.
0359 Clinical Performance Quality of a Precision Oral Appliance Made from Novel Medical Grade Class VI Material
Authors: Murphy Mark , Liptak Len , Kim Sung , Ojeda Yoann
Published: May 2022

Introduction

Oral appliance therapy device quality is an important factor for successful, efficient treatment of Obstructive Sleep Apnea. Poor device quality, defined in this investigation as the remake rate, is costly. A previous investigation reports that 13% of oral appliance therapy devices required remakes, each costing an estimated $300 in lost productivity, fees for remakes, and three weeks of lost therapy. Other investigations associate poor quality with even higher costs and an increased propensity for the patient to discontinue treatment.

Methods

In this retrospective study design, quality data for 34,261 consecutively manufactured oral appliance therapy devices made from a novel medical grade class VI material was collected. Quality data was analyzed in total, and with 30-day and 60-day lag periods. The purpose of the lag periods was to account for the time between manufacture and delivery.

Results

Total remake rates were 1.2% (416/34,261). Total remake rates with a 30-day lag period were 1.3% (416/30,946). Total remakes with a 60-day lag period were 1.5% (416/26,964).

Conclusion

The clinical performance quality for a new precision oral appliance made from a novel medical grade class VI material is encouraging. Remake rates were between 1.2% and 1.5% depending on the lag period, which is directionally favorable in comparison with previously reported remake data.

Support (If Any)

Data provided by ProSomnus Sleep Technologies.
0360 PAP Adherence, Follow-Up, and Telehealth During the COVID-19 Pandemic
Authors: Kim David , Powell Tyler , Brock Matthew , Foster Shannon , Hansen Shana
Published: May 2022

Introduction

Positive airway pressure (PAP) is the gold standard therapy for OSA. However, patient follow-up and adherence to PAP therapy remains variable. With the onset of the COVID-19 pandemic, many sleep centers shifted towards telemedicine. In order to evaluate the impact of telehealth, we assessed the rates of follow-up and PAP adherence among patients newly diagnosed with OSA prior to and after the onset of the COVID-19 pandemic.

Methods

Patients aged 18-75 years enrolled in our military sleep center who met eligibility criteria were divided into a pre-pandemic group and a pandemic group. For the pre-pandemic group, initial and follow-up clinic appointments occurred via face-to-face encounters. For the pandemic group, these clinic appointments occurred via telephone encounters. PAP follow-up was defined as a clinic appointment occurring within 6 months of the initial OSA diagnosis and the onset of PAP therapy. Adequate PAP adherence was defined as usage of the device ≥ 4 hours per night on ≥ 70% of nights during a consecutive 30-day period. Differences among the two groups regarding PAP follow-up, PAP adherence, and demographic data were analyzed.

Results

Eligible patients (n=234) were divided into a pre-pandemic group (n=117) and a pandemic group (n=117). Demographic data for the pre-pandemic group vs. pandemic group included the following: mean age 42.2 vs. 40.3 years; 78.6% vs. 88.0% male; 60.7% vs. 76.9% active duty military, mean BMI 30.1 vs. 30.1; mean AHI 28.5/hr vs. 27.7/hr; mean Epworth Sleepiness Scale score 11.7 vs. 12.0; mean Insomnia Severity Index 16.9 vs. 16.8. The rates of PAP follow-up were 59.0% (pre-pandemic group) vs. 41.0% (pandemic group). The rates of adequate PAP adherence were 34.8% (pre-pandemic group) vs. 25.0% (pandemic group).

Conclusion

There were higher rates of PAP follow-up and PAP adherence among patients seen via face-to-face encounters occurring prior to the onset of the COVID-19 pandemic. While utilization of telehealth in our center did not result in improved outcomes, there may still be utility in offering telehealth to the sleep patient population. Additional studies are needed to identify effective interventions that can be implemented to improve rates of PAP follow-up and PAP adherence.

Support (If Any)

There were higher rates of PAP follow-up and PAP adherence among patients seen via face-to-face encounters occurring prior to the onset of the COVID-19 pandemic. While utilization of telehealth in our center did not result in improved outcomes, there may still be utility in offering telehealth to the sleep patient population. Additional studies are needed to identify effective interventions that can be implemented to improve rates of PAP follow-up and PAP adherence.
0361 PennPALS: An Innovative, Bidirectional Text Messaging System Using PAP Usage Data to Increase Patient Adherence with PAP Therapy
Authors: Jimenez David , Cadman Sara , Watach Alexa , Khan Neda , Hahn Lauren , Bae Charles
Published: May 2022

Introduction

Cloud-based systems that collect PAP data provide patients and providers with near real-time usage information, but a system that identifies/intervenes with patients at risk of PAP non-adherence has not been available to date. The Penn PAP Automated Learning System (PennPALS) is an automated, bidirectional text messaging system that uses PAP data to initiate text messaging conversations to patients in a timely manner.

Methods

PennPALS was created using Way to Health, an evidence-based patient engagement platform, to leverage PAP data, such as daily average hours of use and time spent with a large mask leak, to identify and initiate automated text messages to help patients troubleshoot issues. Depending on their responses, patients were given a pre-defined recommendation via text or escalated to a clinical provider contacting them via phone-call. Two 30-day pilots were conducted, which collectively enrolled 33 patients who were prescribed PAP for the first time.

Results

Most patients were White, Non-Hispanic (54.8%, n=17), males (64.5%, n=20), with a mean age of 52 years. Two patients did not receive a PAP machine by the end of the pilot. PennPALS engaged patients via text message 115 times. Of the 31 patients who started PAP, 7 (22.6%) were adherent from the start of enrollment and only received positive enforcement text messaging. Across the 24 (77.4%) patients that experienced issues, there were 58 text message conversations, which resulted in 32 clinical escalations. Twenty-one (67.7%) patients triggered text messaging interventions for using PAP for < 4 hours/night on average over a 7-day period or experiencing a large mask leak, n=10 (32.3%) and n=11 (35.5%) respectively. At 30-days, 17 (70.8%) of the 24 patients were adherent (i.e. using their PAP at least 4 hours/night on average over the last 7-days). Patient feedback was generally favorable with a Net promoter score (likelihood to recommend) of 68.4 (n=19).

Conclusion

PennPALS effectively identified/intervened with patients at risk of non-adherence to PAP therapy, and the bidirectional text messaging system helped patients become adherent in the first 30 days of treatment. Further testing and longer-term monitoring is needed to examine the effectiveness of PennPALS on long-term PAP adherence.

Support (If Any)
0380 A Pilot Study to Test Patient-Reported Outcomes Visualization Methods in the EHR Note Template for Sleep Medicine Clinicians
Authors: Yar Wail , Kazaglis Louis
Published: May 2022

Introduction

Patient-Reported Outcomes (PROs) are standardized assessments of patient-specific health measures for physical, mental, and social well-being reported directly by patients without provider interpretations. Providers use PROs to efficiently improve the quality of care and empower patients through structured communication. Patient factors are widely acknowledged to affect PROs; however, there is very little data on the effect of provider PRO visualization methods on patient outcomes. This pilot study compares PRO visualization methods to improve readability, provider satisfaction, and patient outcomes in a comprehensive sleep center. We hypothesize that detailed PRO with color-based formatting will improve the clinical diagnoses and provider satisfaction with PRO metrics.

Methods

Twenty-four sleep providers from the Sleep Disorders Center at Cleveland Clinic, consisting of physicians (n=14), fellows (n=3), and nurse practitioners (n=7), were randomly assigned to two equal groups. All sleep providers completed the online pre-intervention survey (71% female), and 23 providers (96%) completed the post-intervention survey four weeks after randomization. Survey questions utilizing 5-point Likert scales inquired about current use and perceived benefit of 3 PROs accompanying new visits: International Restless Leg Syndrome Scale (IRLS), Insomnia Severity Index (ISI), and Epworth Sleepiness Scale (ESS). The standard presented only total scores, while the intervention group received detailed tables of IRLS, ISI, and ESS components with color-stratified total scores. ANCOVA statistical analysis was performed to compare satisfaction, usage, and clinical utility between groups over time.

Results

Current PRO templates were used by 79% of providers. PROs were reported as helpful or extremely helpful by 87% of providers, while only 38% were satisfied or extremely satisfied by the presentation. Compared to controls, the enhanced-visualization group scores improved but did not display significant differences in the likelihood of use (p=0.8), helpfulness (p=0.7), or overall satisfaction (p=0.9); utility in reaching diagnosis demonstrated a trend towards improvement (p=0.051).

Conclusion

PRO enhanced visualization did not demonstrate improvements in provider utility or satisfaction in this study. However, effects are likely limited by small sample sizes. Direct measurement of effects on test ordering and clinical diagnoses may provide further clarity. Future research is needed to enhance the usage of PROs to assess the decision-making process during clinical practice.

Support (If Any)
0386 Long-term Safety During a Clinical Trial of Lower-Sodium Oxybate in Participants With Narcolepsy With Cataplexy
Authors: Bogan Richard , Foldvary-Schaefer Nancy , Skowronski Roman , Chen Abby , Thorpy Michael
Published: May 2022

Introduction

Treatment-emergent adverse events (TEAEs) were analyzed during a 6-month open-label extension (OLE) of a double-blind, placebo-controlled, randomized withdrawal trial (NCT03030599) of lower-sodium oxybate (LXB; Xywav™). LXB is FDA approved for treating cataplexy or excessive daytime sleepiness in patients with narcolepsy aged ≥7 years and for treating idiopathic hypersomnia in adults.

Methods

Participants entered the OLE following rescreening (re-entry) after discontinuing LXB treatment or directly after completing the main study (rollover). Re-entry participants initiated LXB (4.5 g/night) or, if taking sodium oxybate (SXB) during rescreening, transitioned to identical LXB doses (gram-for-gram). Participants titrated (1‒1.5 g/night/week) to a maximum of 9 g/night. TEAEs were assessed in all participants receiving ≥1 LXB dose. TEAE duration represents time from TEAE start to end date (or end of OLE, if TEAE end date unrecorded).

Results

In the analysis population (N=74, mean±SD age=37.6±12.6 years, 66.2% female, 91.9% White), 27 (36.5%) re-entered (after a median [range] of 15.0 [4.0‒33.0] days), and 47 (63.5%) rolled over. Most reported ≥1 TEAE (overall, 58.1%; re-entry, 59.3%; rollover, 57.4%). Overall, the most commonly reported TEAEs were headache (n=7, 9.5%; peak incidence was month 3 [n=5/72]; median [range] duration=1.0 [1‒25] day), nasopharyngitis (n=6, 8.1%; peak incidence was month 6 [n=2/69]; median [range] duration=9.0 [1‒24] days), and dizziness (n=5, 6.8%; peak incidence was month 1 [n=3/74]; median [range] duration=26.0 [1‒181] days). TEAEs were most prevalent in month 3 (n=11/72 [15.3%] reporting a TEAE). No participant reported fall or enuresis; 1 reported nausea (rollover). Most TEAEs were mild or moderate; 2 participants had severe TEAEs (invasive ductal carcinoma [IDC], n=1; dizziness, n=1). Few participants (14.9%) had LXB-related TEAEs, most frequently dizziness (overall, 5.4%; re-entry, 7.4%; rollover, 4.3%). LXB-related TEAEs were more common in participants who re-entered (re-entry, 22.2%; rollover, 10.6%). Seven participants discontinued (re-entry, n=2; rollover, n=5), 3 due to TEAEs (IDC, n=1; apathy, n=1; sleep apnea syndrome, n=1); only apathy was treatment related.

Conclusion

In this long-term study of LXB, safety and tolerability profiles were generally consistent with the known safety profile of SXB. The most common TEAEs were headache, nasopharyngitis, and dizziness.

Support (If Any)

Jazz Pharmaceuticals.
0393 Weight Changes During Treatment With Lower-Sodium Oxybate in a Phase 3 Clinical Study in Patients With Narcolepsy
Authors: Foldvary-Schaefer Nancy , Skowronski Roman , Hickey Luke , Chen Abby , Measey Thomas , Dauvilliers Yves
Published: May 2022

Introduction

Treatment with sodium oxybate (SXB) has been associated with weight loss in patients with narcolepsy. Lower-sodium oxybate (LXB) contains the same active moiety as SXB, with 92% less sodium, and is approved in the US for treatment of cataplexy or excessive daytime sleepiness in patients ≥7 years of age with narcolepsy and for treatment of adults with idiopathic hypersomnia. This analysis assessed weight changes after 14 weeks of open-label LXB treatment in a phase 3 clinical study in patients with narcolepsy (NCT03030599).

Methods

Participants 18‒70 years of age with narcolepsy with cataplexy (taking SXB only, SXB+other anticataplectics, or other anticataplectics, or who were anticataplectic-naive at study entry) began LXB treatment in a 12-week, open-label, optimized treatment and titration period, followed by a 2-week stable-dose period (SDP) on LXB.

Results

Study participants (N=201) had a mean (SD) age of 37.2 (12.2) years. At baseline, mean (SD) weight and body mass index (BMI) were 83.7 (19.2) kg and 28.8 (6.1) kg/m2, respectively; 31.8% of participants (64/201) were normal weight (BMI 18.5 to <25 kg/m2), 31.8% (64/201) were overweight (BMI 25 to <30 kg/m2), and 35.3% (71/201) were obese (BMI ≥30 kg/m2). At the end of SDP, mean (SD) weight and BMI changes in SXB-only (n=45 weight; n=44 BMI), SXB+anticataplectics (n=14), other-anticataplectics (n=23), and anticataplectic-naive (n=65) participants were, respectively, −0.2 (2.5) kg and 0.0 (0.9) kg/m2, −1.0 (1.9) kg and −0.3 (0.6) kg/m2, −2.3 (4.0) kg and −0.8 (1.4) kg/m2, and −2.5 (3.8) kg and −0.9 (1.3) kg/m2. Weight loss ≥5% at the end of SDP occurred in 6.7% of SXB-only, 0.0% of SXB+anticataplectics, 21.7% of other-anticataplectics, and 27.7% of anticataplectic-naive participants. In normal weight, overweight, and obese participants at baseline, mean (SD) decreases in weight at the end of SDP were −1.5 (3.1) kg, −3.3 (3.5) kg, and −2.6 (4.7) kg, respectively (participants who were oxybate-naive at study entry), and −0.1 (1.8) kg, −1.0 (2.4) kg, and 0.2 (2.8) kg, respectively (participants taking SXB at study entry).

Conclusion

In this study, adults with narcolepsy who were oxybate-naive at study entry experienced greater weight loss during LXB treatment compared with adults previously taking SXB.

Support (If Any)

Jazz Pharmaceuticals.
0408 A Narcolepsy Detection Paradigm: Automated Nocturnal Detection and Notification of Sleep Onset Rapid Eye Movement Periods
Authors: Cairns Alyssa , Bogan Richard , Zheng Alex , Bujanover Shay , Lillaney Prasheel , Friedberg Andrew , Black Jed
Published: May 2022

Introduction

Rapid eye movement (REM) sleep detected by polysomnography (PSG) occurring within 15 minutes of nocturnal sleep (sleep onset REM period; SOREMP) is a known biomarker for hypocretin-deficient narcolepsy. However, the SOREMP is often underappreciated when observed in patients undergoing routine diagnostic sleep testing, evidenced by the paucity of further evaluation for hypersomnia in these individuals. To enhance identification of SOREMP episodes, we developed an automated process to detect and advise sleep clinicians of sleep onset REMs. This study aimed to evaluate the impact of automated SOREMP notification on clinician recommendations for narcolepsy diagnostic evaluation and multiple sleep latency test (MSLT) outcomes.

Methods

The automated SOREMP notification program was offered to all sleep clinicians within a large multicenter sleep clinic network. De-identified sleep studies were uploaded to a secure data cloud for real-time automated SOREMP detection. Algorithmic-determined SOREMPs underwent human adjudication by a team of expert registered sleep scorers. Clinicians were advised of the presence of SOREMPs within the interpretation platform via a visual banner. Clinician recommendations and future testing (including MSLTs) were naturalistically tracked.

Results

Of 17,447 sleep studies processed over 3 years, 145 exhibited a SOREMP (0.8%). Five studies were excluded from primary analyses because of a prescheduled MSLT (n=2 narcolepsy; n=2 idiopathic hypersomnia; n=1 “normal”). Of the remaining 140 patients, 19 (14%) were recommended for further narcolepsy evaluation/MSLT; to date, 4 patients have had an MSLT (n=3 narcolepsy; n=1 “normal”). Excluding the PSG SOREMP, MSLT outcomes were #1: 2 SOREMPs and MSL=4.7 min; #2: 3 SOREMPs and MSL=3.0 min; #3: 5 SOREMPs and MSL=4.6 min; #4: 0 SOREMPs and MSL=11.7 min.

Conclusion

This study implemented enhanced identification and subsequent clinician notification of nocturnal SOREMPs using a novel sensitive SOREMP detection paradigm. This methodology resulted in recommendation of 19 patients, who otherwise may have gone undetected, for further narcolepsy evaluation. When conducted, MSLTs most often supported a narcolepsy diagnosis. This is a call to action for medical providers to critically evaluate patients who exhibit a PSG SOREMP, as it may provide a unique opportunity to identify and treat narcolepsy. Further research is needed to better understand the low referral rate.

Support (If Any)

Jazz Pharmaceuticals.
0414 Estimated Prevalence of Idiopathic Hypersomnia in the Wisconsin Sleep Cohort
Authors: Peppard Paul , Plante David , Hagen Erika , Barnet Jodi , Mignot Emmanuel
Published: May 2022

Introduction

Idiopathic hypersomnia (IH) is a neurologic condition characterized by chronic excessive daytime sleepiness despite normal sleep duration in which sleepiness is unexplained by other sleep disorders, behaviors, or other identifiable causes. Population-based prevalence estimates of IH are unavailable, though a recent analysis of a US insured population found ~1/10,000 persons were diagnosed with IH. Here we estimate IH prevalence in the Wisconsin Sleep Cohort (WSC).

Methods

The WSC is an epidemiology cohort recruited from a working population. To characterize IH we used measures of subjective (Epworth Sleepiness Scale, ESS) and objective sleepiness (Multiple Sleep Latency Tests, MSLT), polysomnography, sleep diaries, and extensive questionnaires. IH was defined as the union of: ESS>10; MSLT<8 minutes; <2 sleep-onset REM periods; apnea-hypopnea index (AHI)<15 (we also estimated prevalence using an AHI<5 cutpoint); >=6 hours habitual daily sleep; and non-shift worker. Other explanations for sleepiness were also investigated.

Results

Among 792 WSC participants (48% female, mean age=59 years [range=40-78 years]), we estimate an IH prevalence=3.8%, 95% CI=2.6-5.4%). We arrived at this estimate thusly: of n=792 participants, n=275 (35%) had ESS>10; of these, n=89 had MSLT<8 minutes; of these, n=71 had <2 sleep onset REM periods; of these, n=35 had an AHI<15; of these, n=33 slept >=6 hours/night; and, of these, n=30 were non-shift workers. Comparing the 30 so-defined “IH participants” to non-IH participants, respectively: 57% (IH) vs. 48% (non-IH) (NS) were female, mean age was 57 vs. 59 years (NS), mean AHI was 4.6 vs. 13.3 (by definition of IH, mean AHI was lower for IH participants), mean sleep duration was 7.6 vs. 7.7 hours (NS), and sedative use prevalence was 3% vs. 10% (NS). No IH participants reported a history of heart failure, heart attack or stroke. Prevalence of IH using an AHI cutpoint of 5 (i.e., IH only classified in participants with AHI<5), we find an IH prevalence of 2.4% (95% CI=1.5-3.7%).

Conclusion

Idiopathic hypersomnia may be more prevalent than previously assumed: approximately 2 to 4% of Wisconsin Sleep Cohort participants had evidence of hypersomnia that could not be explained by other sleep disorders, insufficient sleep, shift work or other examined factors.

Support (If Any)

This work was supported by the National Heart, Lung, and Blood Institute (NHLBI, R01HL62252), National Institute on Aging (NIA, R01AG058680) and the National Center for Research Resources (NCRR, 1UL1RR025011) at the US National Institutes of Health, as well as a grant from Jazz Pharmaceuticals.
0428 A National Survey of 1000 Patients’ and 450 Physicians’ Views and Attitudes on Insomnia Care
Authors: Benca Ruth , Bertisch Suzanne , Ahuja Ajay , Mandelbaum Robin , Krystal Andy
Published: May 2022

Introduction

While the importance of restful sleep is espoused by patients and physicians alike, sleep health may not be receiving appropriate consideration during patient visits with HCPs. This study is the first to survey both patients with sleep difficulties as well as physicians who treat insomnia, in order to understand the perspectives of each group.

Methods

Patient and HCP online surveys were conducted by The Harris Poll from September to October 2021 in the USA. Patient participants were adults ≥18 years with a diagnosis of insomnia by an HCP or with self-reported difficulties sleeping for ≥3 nights/week over ≥3 months. The patient survey consisted of 51 questions pertaining to sleep difficulties, interactions with HCPs, and treatment options. The 34-question HCP survey pertaining to approaches and beliefs regarding insomnia diagnosis and management was completed by primary care physicians (PCPs) and psychiatrists.

Results

The respondents included 1001 patients (54% female; mean age 44.6 years) and 452 physicians (300 PCPs, 152 psychiatrists) who had opted-in for surveys, sourced from 100+ panels. Notable findings included that a majority of patients with sleep difficulties reported feeling frustrated (54%), irritated (52%), stressed (51%) and/or reported that their mood is negatively impacted (59%). While nearly all PCPs (98%) and psychiatrists (97%) affirmed that sleep is critical to good health, only 12% of PCPs and 24% of psychiatrists routinely conducted a full sleep history.Regarding treatment, 66% of patients did not think that current treatment options adequately improve their trouble sleeping; while 50% of PCPs felt their patients are satisfied with their current treatment. Moreover, 55% of people with trouble sleeping believed that there is a stigma associated with taking prescription sleep medications.

Conclusion

This first-ever survey of patients with insomnia and doctors treating this condition provides evidence that both groups agree on the importance of sleep and that treatment is often perceived as ineffective. Also of note, relatively few physicians conduct a sleep history and patients report that there is stigma associated with taking medications for insomnia. Most notably, this survey identifies the need to address our limited understanding and the insomnia conversation gap regarding key issues about insomnia treatment.

Support (If Any)

Idorsia Pharmaceuticals, Ltd.
0439 A Polysomnographic Marker of Sleep Quality using Odds Ratio Product are Associated with Insomnia Symptoms in a Dose-Response Relationship
Authors: Bender Amy , Lambing Kari , Gerardy Bethany , Chalmers Eric
Published: May 2022

Introduction

Insomnia is primarily diagnosed with subjective complaints because objective biomarkers are limited. In the current study, we assessed whether a polysomnographic marker of sleep quality (odds ratio product; ORP) was associated with different types of insomnia symptoms.

Methods

416 participants (age 46.2±12.5; 176 females) recorded their sleep with an in-home Type 2 PSG test using the Cerebra Sleep System and filled out sleep questionnaires. Sleep quality was measured using odds ratio product (ORP) derived from frontal EEG channels across the duration of the recording (ORPTRT). On the questionnaires, participants reported whether they experienced any of the following insomnia symptoms at least three times a week: trouble falling asleep, trouble staying asleep, and waking up earlier than desired. Participants were then classified based on the total number of insomnia symptoms reported. An ANOVA, controlling for age, was performed to compare the effect of the number of insomnia symptoms on ORP.

Results

199 participants reported no insomnia symptoms, while the remaining 217 reported at least one symptom three nights a week (1 symptom: n = 62, 2 symptoms: n = 83, 3 symptoms: n = 70). There was a significant effect of number of insomnia symptoms on ORPTRT F(3,414)=3.45, p =.017. There were significant differences between ORPTRT in participants who reported 0 symptoms (.991±.267), and participants who reported 2 symptoms (1.11±.259) (t(282) = -3.57, p <.001), and between 0 and 3 symptoms (1.13±.31 (t(269) = -3.46, p <.001). Even within individuals reporting insomnia symptoms, there were significant differences in ORPTRT between participants who reported 1 and 2 symptoms (p=.024), and 1 and 3 symptoms (p=.029).

Conclusion

The more insomnia symptoms that were reported, the greater the impairment in sleep quality using ORP were found. Further research could explore if treatment interventions aimed at reducing ORPTRT might be useful to help treat insomnia.

Support (If Any)
0458 The Sleep Diary Questionnaire: An Analysis of Meaningful Change in Subjective Total Sleep Time Using Phase 2 and Phase 3 Clinical Trial Data
Authors: Phillips-Beyer Andrea , Kawata Ariane , Kleinman Leah , Flamion Bruno
Published: May 2022

Introduction

The Sleep Diary Questionnaire (SDQ) is a new content-valid 17-item sleep diary adapted from the Consensus Sleep Diary. It assesses key sleep parameters including total time asleep the previous night or “subjective total sleep time” (sTST). People with insomnia value increasing sTST as a key treatment outcome. We estimated meaningful withinpatient change for sTST from two clinical trials in adults with insomnia.

Methods

Data from a 2-week, phase 2 open-label trial of zolpidem (NCT03056053) and blinded data from a 3-month, phase 3 randomized placebo-controlled trial of daridorexant (NCT03545191) were used. In both trials, subjects completed the SDQ daily before and during treatment. Changes in weekly average sTST were calculated using anchor-based analyses that included patient and clinicianreported outcome measures whose correlations with change in weekly average sTST were at least moderate (Spearman correlation coefficient ≥|0.3|). The outcome measures were Insomnia Severity Index, Patient Global Assessment of Disease Severity, Patient Global Impression of Severity, Patient Global Impression of Change, Clinician Global Impression of Severity, and Clinician Global Impression of Change. Distribution-based analyses calculated standard error of measurement (SEM) as supportive evidence. Change estimates from the anchor and distributionbased analyses were “triangulated” to identify a value where they converged.

Results

In the phase 2 trial (N=114), mean increases in sTST from baseline in subjects with meaningful improvements on the anchors were 60.1–83.2 min at day 8 and 55.5–93.5 min at day 15. SEM was 51.1 min at day 8 and 55.5 min at day 15. In the phase 3 trial (N=930, pooled across treatment arms), mean increases in sTST were 36.5–76.2 min at month 1 and 47.3–87.7 min at month 3. SEM was 43.2 min at month 1 and 53.3 min at month 3. Triangulation of these results supported a meaningful change threshold of 55 min.

Conclusion

Our findings support the importance of using sTST to assess insomnia from the patient’s perspective and provide useful information that an increase in sleep time of almost 1 hour is meaningful to patients.

Support (If Any)

This work was funded by Idorsia Pharmaceuticals Ltd.
0467 Preference for Digital CBTI: Changes due to the COVID-19 Pandemic in a Randomized Controlled Trial of CBTI for Middle Aged and Older Adults
Authors: Gumport Nicole , Tutek Joshua , Simpson Norah , Tully Isabelle , Dietch Jessica , Zulman Donna , Rosas Lisa , Palaniappan Latha , Manber Rachel
Published: May 2022

Introduction

Digital CBTI programs are effective at treating symptoms of insomnia. They also have the potential to increase treatment reach, convenience, and affordability for patients, and to reduce long wait times for behavioral sleep medicine providers. The COVID-19 pandemic has instigated an increased reliance on the use of technology for many. Thus, this study evaluates middle aged and older adults before and during the COVID-19 pandemic to assess: (1) differences in treatment modality preference (digital vs. therapist-led CBTI) and (2) sleep-related predictors of treatment modality preference.

Methods

Participants were older adults (N=229, 74% female, mean age=63.14) who were enrolled in the RCT of the Effectiveness of Stepped-Care Sleep Therapy in General Practice (RESTING) study. At baseline, participants rated if they would prefer to access CBTI digitally or with a CBTI therapist, either in person or via telemedicine. After March 2020, in person was no longer listed as an option. Participants completed the Insomnia Severity Index (ISI) and a two-week sleep diary that allowed for an assessment of total sleep time (TST), sleep onset latency (SOL), and wake after sleep onset (WASO). Analyses compared responses to these items from participants completing assessments before March 2020 (Pre-Covid; n=74, 65% female, mean age=62.52) and after March 2020 (During-Covid; n=155, 78% female, mean age=63.44).

Results

Pre-Covid, 26% of participants preferred digital treatment, 47% of participants preferred a therapist-led intervention, and 27% did not express a preference. During-Covid, 35% of participants preferred digital treatment, 32% of participants preferred a therapist-led intervention, and 32% did not express a preference. This difference was statistically significant (c2=4.24, p=0.04). Responses were not significantly different between the first six months and the most recent six months of the pandemic (p=0.60). None of the sleep measures (ISI, TST, SOL, WASO) were associated with treatment modality preference in the full sample, Pre-Covid, or During-Covid.

Conclusion

The COVID-19 pandemic was associated with increased preference for digital CBTI among patients who are 50 and older, regardless of insomnia severity. Findings suggest that digital CBTI may be an acceptable treatment to many individuals with insomnia, thus increasing its dissemination potential.

Support (If Any)

R01AG057500 and T32MH019938
0483 Clinical Model of Community-Based Sleep Education Intervention for Children with IDD
Authors: Fitzpatrick Kasey , Loring Whitney , Malow Beth
Published: May 2022

Introduction

Sleep difficulties are common for children with intellectual and developmental disabilities (IDD). We previously found that implementing the principles of community-based sleep education intervention with children with IDD through a consultative caregiver training model improved key components of sleep and was a feasible model for both providers and caregivers (MacDonald, 2021).

Methods

Record reviews were conducted from a behavioral sleep clinic for children with IDD to evaluate for the reported effectiveness of the recommendations provided on improving sleep and to gather information regarding reported caregiver implementation of recommendations. A clinical psychologist trained in community-based sleep education and IDD met with 43 children, ages 1 to 18 years old with clinical diagnosis of an IDD, and at least one caregiver, to give individualized recommendations for their caregiver-reported sleep issues. These patients were referred to the psychologist by a developmental medical provider or a sleep medical provider after medical evaluation of these concerns. Concerns consisted of sleep onset latency, nighttime wakings, and/or co-sleeping. Patients and caregivers typically met 1 to 3 months after the initial visit to report their success at implementing recommendations and to share if there were any improvements at first follow-up or questions/concerns regarding the recommendations or sleep behavior. In some cases, additional follow-up visits were typically scheduled 1 to 6 months after and these were also reviewed. The notes from these visits were evaluated using qualitative measures and tools modified from Pediatric Sleep and Autism Clinical Global Impressions Scale (Pediatric CGI; Malow, 2016) to determine effectiveness and feasibility.

Results

Qualitative and quantitative measures adapted from Pediatric CGI were used by the record reviewer to evaluate notes. It was observed that 86% of caregivers reported complying with recommendations by the first follow-up and of those who complied, 81% reported improvements in their child’s sleep and/or daytime behavior. Of those who did not comply by first follow-up, only 28% saw improvement. Of those who had second follow-up, 89% of caregivers reported improvement in their child’s sleep and/or daytime behavior.

Conclusion

Time-limited models of community-based sleep educational interventions within a clinical setting are reported by caregivers and clinicians to be an effective method at delivering sleep education to families and improving sleep for children with IDD. Compliance with recommendations was associated with a higher proportion of improvement in sleep and/or daytime behavior.

Support (If Any)

This work was supported by the Vanderbilt Kennedy Center for Excellence in Developmental Disabilities