bluuebunny/crossref_metadata_2025 huggingface dataset:
381 Evening Chronotype Predicts Subjective Sleep Symptom Severity in Pregnant Women with Insomnia Disorder
Authors: Tutek Joshua , Solomon Natalie , Dietch Jessica , Simpson Norah , Manber Rachel
Published: May 2021

Introduction

Evening chronotype is associated with greater reports of insufficient sleep and sleep-related distress. Little research has examined this relationship within the context of pregnancy. This study investigated whether eveningness predicts insomnia severity, sleep effort, dysfunctional sleep beliefs, and sleep reactivity to stress in pregnant women with insomnia disorder.

Methods

Pregnant women with insomnia disorder who spoke English or Spanish enrolled in a clinical trial of cognitive behavioral therapy for insomnia (N = 178; M age = 32.6 years). Before beginning treatment, participants completed the Composite Scale of Morningness (CSM), Insomnia Severity Index (ISI), Glasgow Sleep Effort Scale (GSS), Dysfunctional Beliefs and Attitudes about Stress Scale (DBAS), and Ford Insomnia Response to Stress Test (FIRST). Participants were categorized into evening, intermediate, or morning chronotypes (bottom 25%, middle 50%, or top 25% of CSM scores, respectively). MANCOVA examined whether chronotype predicted higher baseline ISI, GSS, DBAS, and FIRST scores after adjusting for age, gestational week of pregnancy, and language.

Results

Sleep measures collectively differed by chronotype, F(8, 336) = 4.05, p < .001; Wilk’s Λ = .83, partial η-sqd = .09. Follow-up ANOVAs testing individual dependent variables were all significant (partial η-sqd = .04 – .10, p < .05). Pairwise comparisons (Bonferroni-adjusted; p < .05) found that evening types had higher ISI scores than intermediate (M difference = 2.21) and morning types (M difference = 2.30), and higher DBAS scores than morning types (M difference = .95). Morning types had lower FIRST scores than evening (M difference = 5.44) and intermediate types (M difference = 3.89).

Conclusion

Evening chronotype was associated with greater insomnia severity and maladaptive sleep-related cognition than other chronotypes among pregnant women with insomnia disorder. Future research may examine whether differences in chronotype have implications for insomnia treatment outcome during pregnancy, and whether greater morningness confers protection against sleep challenges during the early postpartum period.

Support (if any)

NIH R01 NR013662
402 A wireless patch-based polysomnography system for sleep studies: effect of the 2016 AASM rules on AHI in normal individuals
Authors: de Vries Jantina , Rossi Alessandro , De Francisco Ruben , Adnane Soukaina , Schneider Hartmut , Andries Daniela
Published: May 2021

Introduction

Current home sleep test (HST) devices are limited by an absence of EEG, or by being too cumbersome to use. We developed a wireless PSG system (Onera Health, NL) consisting of four disposable patches to record EEG, EOG, EMG, SaO2, ECG, bioimpedance derived respiratory airflow and effort, airflow via nasal cannula, snoring sounds, body position, actigraphy, and leg movements. Signals are stored on reusable electronic modules attached to each patch.

Methods

We measured PSG hook-up time in 15 healthy laypersons (6 male, 9 female, age 18-to-70 yrs, BMI 29.7±5.2 kg/m2). We also enrolled 6 additional asymptomatic healthy volunteers (2 male, 4 female, age 27-to-33 yrs, BMI 24.3±5.7 kg/m2) with history of occasional snoring, on which we scored the apnea-hypopnea index (AHI) using data from our patch-based PSG system recorded at home. We evaluated scoring using the 2016 AASM rules for hypopneas in comparison to the 2007 AASM rules requiring a greater than 3% fall in SaO2 for obstructive hypopneas.

Results

Mean hook-up time for applying all four patches and electronic modules was 4:42 ± 1:20 min. Mean home sleep efficiency was 89.5 SE 1.9% with an average REM% of 20 SE 6.7%. When comparing the 2016 vs 2007 AASM rules for scoring hypopneas, the AHI increased more than threefold during NREM (9.0 SE 2.0/h vs 2.7 SE 0.8/h; p<0.03) and minimally during REM (11.7 SE 2.3/h and 7.1/h SE 1.8/h; p<0.01), implying an overall increase in the AHI from 3.7 SE 0.8/h to 9.9 SE 1.9/h; p<0.02. One subject changed AHI category from normal to mild (3.6 to 14.4/h), another from mild to moderate (12.7 to 26.3/h) using the 2016 AASM rules.

Conclusion

Our wireless patch-based PSG system is an easy solution for sleep studies at home or in the sleep lab, lowering the burden to conduct large scale epidemiologic sleep studies. The presence of standard EEG signals allows to determine NREM and REM statistics, respiratory and non-respiratory arousal indices, AHI and RERA’s by sleep stages. Preliminary study results show that using cortical arousal criteria for hypopneas, the AHI increase is more pronounced in NREM compared to REM sleep.

Support (if any):
416 The impact of Obstructive Sleep Apnea severity on age-related comorbities: a population-based study
Authors: Silva Mayra , Poyares Dalva , Oliveira Luciana , Andersen Monica , Tufik Sergio , Piovesan Ronaldo
Published: May 2021

Introduction

Although age per se has been considered a risk factor for OSA, evidence suggest OSA in older adults may be less severe and OSA diagnostic criteria might be adjusted for this age group. Concurrently, it is likely the late-onset OSA is a distinct phenotype having different pathophysiological mechanisms, as well as clinical manifestations and consequences. We sought to investigate the clinical consequences of OSA severity in older adults from a representative sample of the older population living in the São Paulo city.

Methods

From the baseline survey including 1042 participants in 2007, 715 were reassessed in 2016 completing full in-lab PSG, health-related questionnaires, blood tests, and blood pressure measurements. Individuals > 60 y.o. (n=199) of both genders were included in the analysis. Participants were stratified according to OSA presence and severity in 3 groups G1 (non and mild OSA n=83); G2 (moderate OSA n=56); G3 (severe OSA n=60). General Linear Model (GLM) tests and Chi-square were carried out.

Results

Participants mean age was 70.02±7.31 and mean body mass index (BMI) 28.61±5.39, 40.71% of men. The only comorbidity associated with OSA severity was arterial hypertension occurring in 61.7% of G3, 46.4% of G4 and 41% of G1 (p=0.04). Severe OSA participants were more likely to use a higher (>2/day) number of medications (p=0.03). Finally, out of all blood tests only cortisol was significantly higher in severe OSA group (p<0.001)

Conclusion

Severe OSA in older individuals of the general population is not associated with metabolic conditions, such as diabetes, but it was associated with hypertension. Severe OSA may be a stressful condition, since it was associated with higher cortisol in this population.

Support (if any)

Associaçao Fundo Incentivo a Pesquisa (AFIP)
421 Elucidating Circadian and Sleep Phenotypes and Relation to Cognitive Impairment in Alzheimer’s Dementia
Authors: Heinzinger Catherine , Wang Lu , Bena James , Bekris Lynn , Foldvary-Schaefer Nancy , Pillai Jagan , Rao Sujata , Rao Stephen , Leverenz James , Mehra Reena
Published: May 2021

Introduction

Although sleep disruption in Alzheimer’s disease (AD) pathogenesis has been described, the role of circadian rhythm dysfunction (CRD) is less understood. We hypothesize greater CRD and sleep disruption with poorer cognitive function in AD compared to normal cognition.

Methods

We examined 3 groups:1)mild cognitive impairment with positive AD biomarkers(MCI-AD),n=18, 2)cognitively normal at high risk for AD(HR)(APOEƐ4 carriers),n=19, 3)cognitively normal APOEƐ4 non-carriers(CL),n=16 (National Institute of Aging, IMMUNE-AD). DNA extraction and APOEƐ4 genotyping were performed under the Cleveland Clinic Lou Ruvo Center for Brain Health Aging and Neurodegenerative Disease Biobank. We evaluated actigraphy-based (Motionlogger MicroWatch, Ambulatory Monitoring,Inc®) sleep (wake episodes(WE), total sleep time(TST), sleep efficiency(SE), sleep fragmentation index(SFI)) and circadian (mesor, amplitude, robustness, sleep regulatory index(SRI), intradaily stability) predictors and sleep study-based (ApneaLink Air by ResMed®) predictors (apnea hypopnea index(AHI,3% desaturation) and recording time<90%SaO2) across the groups and assessed association with cognition (Mini-Mental State Exam(MMSE)). Analysis of variance (ANOVA) or Kruskal-Wallis with Bonferroni adjustment was used for cross-group comparisons. ANCOVA assessed cross-group association of MMSE and sleep/circadian indices. Models were adjusted for age, sex, race, education, and BMI.

Results

Age differed across MCI-AD, HR, and CL groups (68.4±6.2,71.2±3.7,73.7±3.7 respectively,p=0.008). MCI-AD had more WE than HR and CL (14.4±5.6,10.9±3.9,10.9±3.5 respectively,p=0.033). In MCI-AD, the following associations were observed: 5% increase in SE was associated with 0.49 point higher MMSE (coefficient0.49, 95%CI[0.03,0.95],p=0.038), 1 hour increase in TST was associated with 0.81 point higher MMSE (coefficient0.81, 95%CI[0.24,1.37],p=0.006), and 1 unit increase in SFI was associated with 0.36 point lower MMSE (coefficient-0.36, 95%CI[-0.64,-0.08],p=0.013). Key measures differed: CLs had lower AHI, MCI-AD had less TST SaO2<90%, MCI-AD had the largest and HR the lowest SFI, and MCI-AD had lesser robustness but higher mesor and amplitude.

Conclusion

In this comparative study of carefully AD biomarker-phenotyped and APOEƐ4-genotyped patients and normal cognition controls, less sleep time and more fragmented sleep are associated with poorer MMSE scores in MCI-AD. Preliminary results show cognitively normal participants at risk of AD(HR) do not show CRD seen in MCI-AD and are more consistent with controls (CL).

Support (if any)

Catalyst Award. MCI cohort: Alzheimer’s Association, 2014-NIRG-305310. IMMUNE-AD, R01AG022304. CADRC, P30 AG062428. Jane and Lee Seidman Fund.
435 Single Session CBT to Improve PAP Initiation and Adherence among Veterans with OSA
Authors: Bishop Todd , Walsh Patrick , Stecker Tracy , Speed Katrina , Ashrafioun Lisham , Stepnowsky Carl , Kuna Samuel , Pigeon Wilfred
Published: May 2021

Introduction

Obstructive sleep apnea (OSA) is a condition that is prevalent, pernicious, and linked to the development and exacerbation of several disease processes. Positive airway pressure (PAP) is a highly efficacious intervention; however, initiation and adherence rates are poor. This represents a critical gap in care and a missed opportunity to reduce morbidity and mortality associated with OSA. The present study piloted a single session of cognitive behavioral therapy for treatment seeking (CBT-TS) among veterans diagnosed with obstructive sleep apnea and newly prescribed PAP.

Methods

Participants were asked to complete assessments at baseline and at two- and four-weeks post-intervention. A sample of 40 Veterans were enrolled in the study and completed a baseline interview, 27 completed CBT-TS. A matched comparison group of 64 veterans who did not receive the intervention was constructed using electronic medical record and PAP adherence data. Mann Whitney U and Chi Square tests were used to examine group differences in initiation and adherence.

Results

Participants who completed the CBT-TS session were more likely to initiate PAP (at least 3 consecutive nights of use) as compared to those receiving treatment as usual (TAU) [(CBT-TS; 96.3%; 26/27) versus (TAU; 64.1%; 41/64); X2(1, N = 91) = 10.16, p = .001]. Participants in the CBT-TS group also used their PAP devices for a greater number of nights over the first month than the comparison group [(CBT-TS; M = 21.7 (SD = 8.9), Mdn = 26.0) versus (TAU; M = 14.4 (SD = 12.6), Mdn = 15.5); U = 555.0, p = .007] and were more likely to use the device in an adherent manner (i.e., ≥4 hours use in an evening); [(CBT-TS; M = 15.1 (SD = 11.2); Mdn = 15.0) versus (TAU; M = 10.3 (SD = 11.2), Mdn = 6.5); U =630.0, p = .038].

Conclusion

These preliminary data suggest that CBT-TS may have utility in increasing initiation of PAP and subsequent treatment adherence among Veterans diagnosed with OSA and newly prescribed PAP.

Support (if any)

This work was supported by the VA Center of Excellence for Suicide Prevention in the Finger Lakes Healthcare System.
438 Rapid Eye Movement Rebound After Continuous Positive Airway Pressure in Co-Morbid Obstructive Sleep Apnea and Fibromyalgia
Authors: Tapia Gregory , Chakraborty Sthitadhi , Padiyara Julia , Khurshid Abid , Rao Murali , Meresh Edwin
Published: May 2021

Introduction

Fibromyalgia (FM) is a chronic pain condition that is associated with poor sleep quality and may present with obstructive sleep apnea (OSA). In OSA patients without FM, previous research has demonstrated a 57% relative increase in rapid eye movement (REM) sleep duration following treatment with continuous positive airway pressure (CPAP). However, there is limited data on REM rebound in patients with co-morbid FM and OSA. Patients with FM are often prescribed medication, like opioid analgesics, that decrease REM sleep. Additionally, pain perception may be altered by decreased REM duration. In the context of a national opioid crisis, it is imperative to explore how nonpharmacological options for treatment of co-morbid FM and OSA may improve REM sleep duration.

Methods

Following IRB approval at a university-affiliated teaching hospital, an electronic medical chart review was completed on patients diagnosed with FM and OSA who received polysomnography testing (PSG) and subsequent CPAP titration treatment. REM duration and REM total sleep time (TST) percentages were reviewed at baseline PSG and after CPAP titration.

Results

FM with OSA (n = 30). Mean age: 50.87, female: 28 (93%), male: 2 (7%). Baseline PSG: mean REM duration 34.47 minutes, mean REM TST 11.03%. After CPAP titration: mean REM duration 56.78 minutes, mean REM TST 18.84%. Pre- and post-CPAP titration REM TST percentage increased from 11.0% to 18.8%, indicating a mean difference of 7.8% (p < 0.001) and a 71% relative increase in REM TST percentage duration.

Conclusion

These findings suggest delivery of CPAP to patients with FM and OSA improved REM sleep duration. The role of sleep in FM and pain severity is underexplored. Given the potential of chronic opioid use in patients with FM, treatment of OSA with CPAP may be a nonpharmacological alternative to pain management. Future studies are needed to see if REM rebound is associated with wellbeing, including perceived sleep quality and decreased pain perception.

Support (if any):
450 Cellular Energy Monitoring for Diagnosis and Management of Therapy for Sleep Disordered Breathing
Authors: Hatch Guy
Published: May 2021

Introduction

Polysomnogram (PSG) monitoring, including pulse oximetry, is the current diagnostic standard in sleep medicine. However, potentially confounding aspects of PSG testing include: test site other than the subject’s normal bed, distracting sensors and wires, subjective interpretation of complex recorded signals, and limited sensitivity to relevant phenomena. There is currently an unmet need for a sleep test that is more clinically effective than PSG, and that can be administered in the subject’s normal sleeping environment. Additionally, confirmation that home therapy has been optimized cannot be achieved by PSG titration.

Methods

A recent proof of concept (POC) study of the armband-wearable Reveal Cellular Energy Monitor (CE monitor) directly compared its data product, Cellular Energy Index (CEi), with PSG data. Scoring methods were adapted from AASM guidance for interpretation of PSG data. At-home recording with the CE monitor was also performed prior to and following PSG studies. At-home incremental adjustment of APAP settings and mask selection was documented with CE monitoring and compared with the information recorded by the home APAP machine.

Results

The comparison of the POC data consistently found the CE monitor to be more sensitive and responsive to hypoxic stress than the PSG pulse oximeter during primary snoring. Obstructive and central apnea events were detected by both, but the CE monitor provided finer resolution of the breath-by-breath effort of breathing compared with PSG RIP and nasal sensors. At-home CE monitor optimization of therapy was documented to often differ from the settings and mask selection determined by PSG titration, and resulted in ‘normal’ sleep breathing data.

Conclusion

All diagnostically-relevant physiologic responses detected by PSG were also detected by the CE monitor. Evidence of cellular hypoxia in the skin, by CE monitor, was consistently recorded during prolonged periods of ‘primary snoring;’ i.e., SpO2 is less sensitive to hypoxic stress during sleep than CEi. Breath-by-breath effort is detected by the CE monitor.

Support (if any)

The POC study costs at UCSF were paid by Reveal Biosensors, Inc.
476 Sleep-Disordered Breathing is More Predictive than Obesity of Increased Left Ventricular Mass Index in Bariatric Surgery Patients
Authors: Usama Muhammad , Wang Lu , Jin Jian , Milinovich Alex , Aylor Joan , Kaw Roop , Kashyap Sangeeta , Cetin Derrick , Aminian Ali , Kempke Nancy , Mehra Reena , Aboussouan Loutfi
Published: May 2021

Introduction

Obesity and obstructive sleep apnea (OSA) are associated with left ventricular hypertrophy and increased cardiovascular risk. Alternatively, the “obesity paradox” describes an improved prognosis from heart failure in obesity, though potentially attributable to confounding/bias. We sought to determine the contributions of obesity and sleep-disordered breathing (SDB) to left ventricular function and morphology in bariatric surgery candidates.

Methods

Patients undergoing polysomnography prior to bariatric surgery from 2011–2018 had demographic (age, gender, race), anthropometric (body mass index [BMI], neck circumference), comorbidities (atrial fibrillation, coronary artery disease, diabetes, hypertension, hyperlipidemia), echocardiographic and sleep-disordered breathing (apnea-hypopnea index [AHI], peak end-tidal CO2 [etCO2]) variables retrospectively examined. The echocardiographic visit closest to polysomnogram within two years was selected with missing values filled by available values within 6 months. Linear regression assessed the relationship of BMI, AHI, and etCO2 with left ventricular mass index (LVMI) after adjustment of demographics and comorbidities. Echocardiographic measures were logarithm transformed before regression analysis. Coefficients and 95% confidence intervals (CI) were calculated by exponential transformation. The analysis was performed based on an overall significance level of 0.05 using SAS software (version 9.4, Cary, NC).

Results

The total of 832 patients had 24% males, mean age 48.8±12, 60% white, and BMI:49.4±9.5kg/m2. Ejection fraction (%) was 60.0±7.0, and LVMI (g/m2): 80.9±23.7. In adjusted models, LVMI decreased by 2.1% for each 5kg/m2 increase in BMI (coefficient=0.979, 95%CI 0.961–0.997, p=0.022) and increased by 4.3% for each 5 mmHg increase in etCO2 (coefficient=1.043, 95%CI 1.013–1.073, p=0.005). Without adjustment, patients with AHI ≥ 5 had 15.3% higher LVMI than non-OSA group (coefficient=1.153, 95%CI 1.034–1.286, p=0.011) and moderate/severe OSA was associated with a 7.6% higher LVMI than those with AHI<15 (coefficient 1.076, 95%CI 1.003–1.153, p=0.040), but not statistically significant after adjustment.

Conclusion

In obese patients, nocturnal hypoventilation rather than obesity may have adverse influences on left ventricular morphology. Future studies should focus on clarifying whether obesity is truly protective in terms of LV mass, i.e. reflective of paradox versus a product of bias. The potential benefit of identifying/treating SDB in bariatric surgery candidates to mitigate cardiovascular risk also deserves further investigation.

Support (if any)

Cleveland Clinic Transformative Resource Neuroscience Award
479 The association of QTc and QT Variability with Severity of Sleep Disordered Breathing
Authors: Patel Salma , Zareba Wojciech , Couderc Jean-Philippe , Xia Xiaojuan , Woosley Raymond , Patel Imran , Combs Daniel , Mashaqi Saif , Parthasarathy Sairam
Published: May 2021

Introduction

The apneas and hypopneas that characterize sleep-disordered breathing (SDB) are associated with QTc prolongation and increased QT variability. There have been mixed results as to whether QTc and QT variability increase with increasing SDB severity. This study assesses whether QTc prolongation and QT variability are likely to increase with increasing severity of SDB in a large multi-center cohort.

Methods

200 subjects with no SDB and approximately 600 with three levels of SDB (mild, moderate, severe) were randomly selected from the Sleep Heart Health study and matched by age, gender and BMI. SDB was defined as an apnea/hypopnea index ≥5. Respiratory and electrocardiograms (ECG) signals from polysomnography studies were analyzed. Bazett’s heart rate correction was used to calculate QTc. QT variability was measured as standard deviation of QT intervals (SDQT) and short-term interval QT variability (STVQT), at 5-minute intervals. Subjects were excluded if there were missing data or low-quality ECG.

Results

Seven hundred and seventy-one subjects (age 68±10 years, 51% female, 92% Caucasian) were included. One hundred and sixty-five subjects had no SDB, 235 mild, 195 moderate and 176 had severe SDB. The mean (SD) QTc was 422(29), 411(26), 419 (34) and 418 (36) ms for the no SDB, mild, moderate, and severe SDB groups, respectively (p=0.017). The mean (SD) STVQT was 7 (9), 11 (16), 8 (9) and 9 (11) for the no SDB, mild, moderate severe SDB groups, respectively (p=<0.001). The mean (SD) STVQT was 3 (2), 4 (4), 4 (3) and 4(4) for the no SDB, mild, moderate severe SDB groups, respectively (p=<0.001). There was no statistically linear relationship between QT prolongation or QT variability and SBD severity.

Conclusion

QTc duration and QT variability were not increased with SDB severity.

Support (if any)

American Academy of Sleep Medicine Foundation (203-JF-18), National Institutes of Health (HL126140), University of Arizona Health Sciences Career Development Award (5299903), and University of Arizona Faculty Seed Grant (5833261)
483 Neuroanatomical and Neurofunctional Correlates of Unexplained Excessive Daytime Sleepiness
Authors: Cook Jesse , Plante David
Published: May 2021

Introduction

Excessive daytime sleepiness (EDS) frequently presents as a secondary symptom, but some experience EDS in the absence of an explanatory medical condition, psychiatric illness, sleep disorder, or medication/substance use. The neurobiology underlying unexplained EDS (uEDS) is poorly understood, which contributes to the existing limitations in uEDS classification, assessment, and treatment. This investigation was designed to identify potential neuroanatomical and neurofunctional correlates of uEDS.

Methods

Data were acquired from the open-access Stockholm Sleepy Brain (SSB) Project, which included either young (20–30 years old) or older (65–75 years old) adults. SSB criteria ruled out common EDS explanations. A uEDS sample (N = 18; Percentage Female = 33%; Percentage Young = 33%) was established using Epworth Sleepiness Scale (ESS) ≥ 11. Age-and-sex matched controls without EDS (noEDS) were identified. T1-weighted MRI and resting-state fMRI (rs-fMRI) data were compiled for each subject, as well as depression, anxiety, and global health self-ratings. Processing pipelines were performed on T1-weighted and rs-fMRI data. Neuroanatomical analyses compared groups using voxel-based morphometry and across gray matter (GM), white matter (WM), and cerebral spinal fluid volume. Threshold free cluster enhancement was used across all neuroanatomical comparisons. For neurofunctional analyses, seed-based connectivity analysis was performed with a seed placed in the left hemisphere of the medial prefrontal cortex (MNI coordinates: 2 -46 12). Fischer Z-transformed functional connectivity maps were compared across groups. Depression, anxiety, and global health scores were included as covariates and corrections were applied for multiple comparisons, across all analyses.

Results

Group characteristics were comparable, except for ESS. Significantly increased GM volume (middle occipital gyrus and precuneus) was associated with uEDS, relative to noEDS. Robust, bilateral increases in WM matter (thalamus, cerebellum, and middle frontal gyrus) were observed for uEDS, relative to noEDS. No significant group differences were observed in rs-fMRI.

Conclusion

Significant neuroanatomical alterations were associated with uEDS that included increases in both GM and WM. These findings converge on previous research associating anatomical differences within the default mode network with uEDS. Future research using more sensitive quantitative measures of WM is warranted.

Support (if any)

This project was supported by a National Institute Nursing Research grant (NR018288).
484 Solriamfetol Titration & AdministRaTion (START): Physician titration strategies in a hypothetical patient with narcolepsy
Authors: Singh Haramandeep , Hyman Danielle , Parks Gregory , Chen Abby , Baldys Beth , Ito Diane , Thorpy Michael
Published: May 2021

Introduction

Solriamfetol (Sunosi®), a dopamine/norepinephrine reuptake inhibitor, is approved (US and EU) to treat excessive daytime sleepiness (EDS) in adults with narcolepsy (75–150 mg/day) or obstructive sleep apnea (OSA) (37.5–150 mg/day). Patient characteristics, comorbidities, and other EDS medications can influence treatment strategies. To understand factors physicians consider when initiating solriamfetol, this study analyzed titration strategies for a hypothetical patient.

Methods

This virtual, descriptive, cross-sectional, qualitative survey enrolled US-based physicians treating patients with EDS due to OSA and/or narcolepsy. Responses to 4 open-ended questions regarding a hypothetical patient were recorded. Patient scenario: 32-year-old woman with narcolepsy (Epworth Sleepiness Scale score=8) using an amphetamine stimulant (35 mg/day) and sodium oxybate (6 g/night) for 6 months and occasionally experiencing non-use-limiting but bothersome adverse events (AEs) with the stimulant. Content analysis of the recordings identified themes in the responses; a trained linguist captured language choices/patterns.

Results

Twenty-six physicians (neurologists, n=7 [27%]; internists/family practitioners, n=7 [27%]; pulmonologists, n=6 [23%]; psychiatrists, n=5 [19%]; otolaryngologists, n=1 [4%]) representing 781 patients on stable solriamfetol doses participated; 19 (73%) were board-certified in sleep disorders. Physicians had been treating narcolepsy a mean 15.7±6.6 years. Most (21 [81%]) thought the patient appropriate for solriamfetol, 3 (12%) thought not appropriate, and 2 (8%) thought appropriateness depended on other factors. Sixteen physicians (62%) suggested adjusting her stimulant, 3 (12%) the stimulant and sodium oxybate, and 1 (4%) neither. Nineteen (73%) would titrate solriamfetol per the label, with 13 (50%) aiming for 75 mg/day and 8 (31%) for 150 mg/day. Physicians emphasized stopping the stimulant before starting solriamfetol: 10 (39%) would taper down before starting solriamfetol, 7 (27%) while starting solriamfetol, and 1 (4%) while aiming to eventually switch; 8 (31%) would discontinue abruptly. Nineteen physicians (73%) would not change their approach if the stimulant dose were 60 mg/day. Most clinicians would change their approach if AEs occurred while starting solriamfetol by taking a slower or more gradual approach, while some would titrate off the stimulant more aggressively.

Conclusion

Physicians considered existing medications and potential AEs in their titration strategy when initiating solriamfetol.

Support (if any)

Jazz Pharmaceuticals
489 Pivotal Phase 3 Study of FT218, a Once-Nightly Sodium Oxybate Formulation, in Patients With Narcolepsy: REST-ON Primary Results
Authors: Kushida Clete , Shapiro Colin , Roth Thomas , Thorpy Michael , Rosenberg Russell , Corser Bruce , Ajayi Akinyemi , Dubow Jordan , Seiden David , Dauvilliers Yves
Published: May 2021

Introduction

Sodium oxybate (SO) is an effective treatment for patients with narcolepsy; however, currently available SO formulations require twice-nightly dosing. The purpose of this study was to evaluate efficacy and safety of FT218, an investigational once-nightly controlled-release SO formulation, for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy types 1 (NT1) and 2 (NT2).

Methods

This was a randomized, double-blind, placebo-controlled, multicenter study in patients with narcolepsy ≥16 years old. Patients were randomized 1:1 to receive FT218 or matching placebo: 4.5 g/night for 1 week, 6.0 g/night for 2 weeks, 7.5 g/night for 5 weeks, and 9.0 g/night for 5 weeks (maximum treatment duration, 13 weeks). Coprimary endpoints were mean sleep latency (minutes) on maintenance of wakefulness test (MWT), Clinical Global Impression-Improvement (CGI-I) of sleepiness, and weekly number of cataplexy attacks (NCAs; NT1 only).

Results

A total of 212 patients were randomized and received study treatment (FT218, n=107; placebo, n=105). FT218 showed significant (P<0.001) improvement vs placebo in mean sleep latency on MWT for all evaluated doses; LS mean difference (minutes) between FT218 and placebo was 6.13 at 9.0 g (week 13), 6.21 at 7.5 g (week 8), and 4.98 at 6.0 g (week 3). A higher proportion of patients receiving FT218 were much/very much improved on CGI-I vs placebo (72% vs 31.6% at 9.0 g; 62.6% vs 22.8% at 7.5 g; and 40.1% vs 6.1% at 6.0 g; all P<0.001). LS mean difference between FT218 and placebo in mean weekly NCAs was significant (P<0.001) for all doses: −6.65 at 9.0 g, −6.27 at 7.5 g, and −4.83 at 6.0 g. The most common adverse reactions were nausea, vomiting, headache, dizziness, enuresis, and decreased appetite.

Conclusion

All evaluated doses of FT218 showed significant improvement vs placebo in mean sleep latency on MWT, CGI-I, and weekly NCAs. FT218 was generally well tolerated and the most common adverse events were consistent with known side effects of SO.

Support (if any)

Avadel Pharmaceuticals.
491 Efficacy of FT218, a Once-Nightly Sodium Oxybate Formulation, by Narcolepsy Subtype: A Post Hoc Analysis From the REST-ON Study
Authors: Roy Asim , Morse Anne Marie , Dubow Jordan , Seiden David , Bogan Richard
Published: May 2021

Introduction

FT218 is an investigational, once-nightly, controlled-release formulation of sodium oxybate for the treatment of narcolepsy. The purpose of this post hoc analysis of the REST-ON study was to evaluate the effect of FT218 on measures of excessive daytime sleepiness (EDS) in patients with narcolepsy subtypes 1 (NT1) and 2 (NT2).

Methods

This was a randomized, double-blind, placebo-controlled, multicenter study in patients with narcolepsy ≥16 years old. Patients were stratified by narcolepsy subtypes and randomized 1:1 to receive FT218 or matching placebo: 4.5 g/night for 1 week, 6.0 g/night for 2 weeks, 7.5 g/night for 5 weeks, and 9.0 g/night for 5 weeks (maximum treatment duration, 13 weeks). Assessments of EDS included mean sleep latency (minutes) on maintenance of wakefulness test (MWT) and Clinical Global Impression-Improvement (CGI-I) in sleepiness.

Results

A total of 190 patients were included in the modified intent-to-treat population (NT1: FT218, n=72; placebo, n=73; NT2: FT218, n=21, placebo, n=24). Patients with NT1 or NT2 receiving FT218 had significant improvement in MWT. LS mean difference in mean sleep latency (minutes) vs placebo for NT1 was 5.97 for 9.0 g (week 13), 7.02 for 7.5 g (week 8), and 4.89 for 6.0 g (week 3; all P<0.001), and for NT2, 6.27 for 9.0 g (P=0.020), 4.01 for 7.5 g (P=0.162), and 5.33 for 6.0 g (P=0.020). A higher proportion of NT1 patients receiving FT218 had significant improvement on CGI-I vs placebo (9.0 g: 75.5% vs 35.9%; 7.5 g: 66.9% vs 27.9%; 6.0 g: 39.9% vs 7.8%; all P<0.001). A higher number of NT2 patients receiving FT218 were consistently rated as much/very much improved vs placebo, based on descriptive statistics. FT218 was generally well tolerated.

Conclusion

FT218 had similar efficacy on EDS at evaluated doses in NT1 and NT2, with improvement in MWT and CGI-I greater than placebo. FT218 may provide effective treatment for EDS in patients with narcolepsy, with or without cataplexy.

Support (if any)

Avadel Pharmaceuticals.
496 Do Patients and Healthcare Providers Have Similar Perceptions of Available Narcolepsy Educational Materials and Treatment Options?
Authors: Patterson Mark
Published: May 2021

Introduction

Studies have shown that patients typically retain <50% of the information communicated to them by their healthcare providers. This lack of retention can lead to serious problems and misunderstandings regarding the condition, its treatment, and course. The goal of this study was to compare the information sleep specialists report providing to patients with the materials narcolepsy patients recall receiving.

Methods

Deidentified on-line surveys were submitted to active members of the American Academy of Sleep Medicine and to patients with narcolepsy Type 1 (NT1) and Type 2 (NT2) via the cloud-based software service company SurveyMonkey. These patients were recruited from the private Facebook group ‘Doctors and Narcoleptic Patients’.

Results

Results were received from a total of 75 patients (68% NT1, 29% NT2, 3% uncertain type; mean time since diagnosis: 11 years) and 18 sleep specialists (mean time in practice: 22 years). Physicians reported that their practices provided written material about narcolepsy to patients 69% of the time. By contrast, only 32% of patients recall receiving written information. Regarding treatment options, the groups reported variable results, with 94% of doctors/86% of patients discussing modafinil/armodafinil, 89% of providers/68% of patients communicating about amphetamines/methylphenidate, and 83% of physicians/47% of patients considering sodium oxybate. Additionally, only 56% of physicians were aware of narcolepsy patient advocacy organizations.

Conclusion

With the ready availability of social media and the exchange of oft inaccurate medical information, it is essential that physicians supply their patients with accurate up-to-date materials, especially following the diagnosis of a life-altering condition such as narcolepsy. This study suggests that there is a mismatch between the information which physicians believe they are providing and the materials the patients recall receiving. In addition to the medical care sleep specialists provide, patients and their families frequently rely on support from condition-specific organizations. Health care providers should be aware of the local and national organizations and supply their patients with contact information in an effort to provide a more holistic approach to medical care. Efforts are necessary to educate physicians about their patients’ needs for on-going care, distinct from that provided solely in the clinical setting.

Support (if any):
497 Clinical Presentation Prior to Idiopathic Hypersomnia Diagnosis Among US Adults: A Retrospective, Real-World Claims Analysis
Authors: Saad Ragy , Ben-Joseph Rami , Prince Patricia , Stack Catharine , Bujanover Shay , Taylor Ben
Published: May 2021

Introduction

Idiopathic hypersomnia (IH) is a rare, serious central hypersomnolence disorder for which there are no FDA-approved medications available. A retrospective study was conducted to characterize newly diagnosed patients with IH in the United States. Here, we report morbidity and comorbidity claims prior to IH diagnosis.

Methods

Claims from the IBM® MarketScan® database were analyzed between January 2014 and September 2019. The general population cohort included all adults with ≥12 months of continuous enrollment. From this population, a cohort with newly diagnosed IH was identified, defined as ≥2 claims with an IH diagnosis code ≥1 day and ≤180 days apart, and without an IH diagnosis in the 12 months prior to cohort entry. Patients without continuous medical/prescription coverage (enrollment gaps >30 days) in the 12 months prior to cohort entry were excluded. Claims with diagnoses for select morbid/comorbid conditions were identified from 12 months prior to cohort entry for the IH and general population cohorts and summarized using descriptive statistics. A sensitivity analysis was conducted on IH patients with the diagnosis code recorded in the primary position (“primary IH”) on the claims to understand the effects of applying a more specific definition of IH.

Results

Of the general population cohort (N=32,948,986; mean age, 42 years; 52% female), 4,980 (0.015%) newly diagnosed IH patients were identified (mean age, 43 years; 67% female). Sleep-related morbidities in the 12 months prior to cohort entry included narcolepsy type 2 (17%/0.1%) and hypersomnia (10%/0.2%) for the IH/general population cohorts, respectively. Common comorbidities were sleep apnea (50%/4%), mood disorders (32%/8%), depressive disorders (31%/7%), anxiety disorders (31%/9%), hyperlipidemia (30%/20%), headache/migraine (24%/7%), diabetes or use of diabetes/obesity medication (20%/12%), hypertension (15%/10%), and cardiovascular disease (14%/8%) for the IH/general population cohorts, respectively. Common morbidities/comorbidities for the primary IH cohort (n=2,205) were generally similar to the overall IH population.

Conclusion

Compared with the general MarketScan® population, morbidities/comorbidities were more common for IH patients across all conditions analyzed, including sleep disorders and psychiatric, cardiometabolic, and cardiovascular disease. With cardiovascular risk factors common upon diagnosis of IH, therapies that do not increase cardiovascular risk are warranted.

Support (if any)

Jazz Pharmaceuticals
501 Clinical PK of XW10172 for Once Nightly Therapy in Patients with Narcolepsy or Sleep Disorders in Neurodegenerative Diseases
Authors: Canafax Daniel , Xiang William , Xiang Jia-Ning
Published: May 2021

Introduction

Patients with narcolepsy and patients with sleep disorders secondary to neurodegenerative diseases have been shown to respond to oxybate. To overcome the limitations of current oxybate therapies, we designed XW10172, a new chemical entity and GABA-B agonist with no sodium or other cation content and for once nightly dosing. The objectives of two clinical studies were to assess the XW10172 pharmacokinetics (PK), pharmacodynamics (PD) and safety/tolerability in normal study participants.

Methods

Two XW10172 studies in healthy participants assessed ascending single and multiple doses, comparison to sodium oxybate in immediate release (IR) and extended release (ER) formulations. PK parameters were calculated from concentration vs. time data. Safety and tolerability were assessed by monitoring adverse events, laboratory tests, and vital signs.

Results

To date, 84 study participants received XW10172 and the PK from single and multiple dose administration showed doses of 0.1 to 7.25 g had a mean oxybate half-life range of 0.5 to 1.3 hours. Oxybate levels from the drug were about 6-fold higher than XW10172 levels. Oxybate PK from XW10172 (IR) was the same as from equal molar doses of sodium oxybate. XW10172 (ER) formulations showed delayed Tmax with extended oxybate exposure compatible with single nightly dose therapy. PK-PD assessment of somnolence, the desired pharmacologic effect, showed a concentration-effect relationship (Cmax p=0.0004, AUC p<0.0001). XW10172 was generally well tolerated and adverse events were those known to be associated with oxybate.

Conclusion

These data support progression of XW10172 (ER) in further clinical development studies to assess this once nightly GABA-B agonist therapy for the treatment of patients with various sleep disorders.

Support (if any)

XWPharma
510 A Profile of Physical Performance Variables in an Out-Patient Adult Population with Narcolepsy
Authors: Tadrous Ragy , Broderick Julie , Murphy Niamh , Slattery Lisa , Quinn Gillian , O’Rourke Deirdre
Published: May 2021

Introduction

Narcolepsy can significantly impact the physical and mental wellbeing of people with narcolepsy, and has been associated with significant reductions in quality of life and physical performance. People with narcolepsy demonstrate many barriers to being physically fit and active, such as sleepiness and social isolation. Despite physical functioning and vitality being the most affected domains of health-related quality of life in this cohort, little is known about how physical performance variables are affected in people with narcolepsy.

Methods

This cross-sectional study profiled the physical performance of adults with narcolepsy attending the Narcolepsy Centre located in St. James’s Hospital. Participants underwent a physical performance test battery that investigated cardiopulmonary fitness, physical activity, muscle strength and endurance. Furthermore, health-related quality of life (HRQoL), symptom severity and sedentary behaviour was ascertained through self-report questionnaires.

Results

A total of 23 participants were recruited in this study. The majority of participants were female (n=13, 56.52%) and the mean age was 31.53 (± 13.17) years. Physical performance was generally found to be lower than age-and-gender matched normative values for cardiopulmonary fitness, physical activity and muscle strength and endurance. Participants’ completed 42.20 ± 21.41 minutes of moderate-vigorous physical activity daily as measured by actigraphy. Considerable sedentary behaviour was objectively measured in this sample (10.21 hours). Symptom severity was high as measured by the Epworth Sleepiness Scale and the Narcolepsy Severity Scale, and participants reported reduced quality of life when compared to general population norms (US, UK, France and Norway).

Conclusion

Markedly reduced physical performance was identified in this sample of people with narcolepsy, irrespective of participant age, gender and BMI. Future research should explore the role of exercise in improving the physical fitness in people with narcolepsy, and the influence of exercise on HRQoL and symptom severity in this cohort.

Support (if any)

This study was completed as part of Mr Ragy Tadrous’ Master of Science (MSc) degree in Trinity College Dublin. This degree was co-sponsored by the Physiotherapy Department in St. James’s Hospital, Dublin.
518 Preliminary report on the efficacy of behavioral therapy for insomnia in shift work disorder: a randomized control trial
Authors: Vallieres Annie , Garnier Severine , Pappathomas Alric , Mérette Chantal , Bastien Célyne
Published: May 2021

Introduction

Around 33% of shift workers suffer from shift work disorder (SWD). SWD includes insomnia and sleepiness related to the atypical work schedule. Most SWD treatments rely on light therapy or pharmacology. Few studies explored CBT-I efficacy for insomnia in shift work and reported promising results. The study aims to evaluate the efficacity of a behavioral therapy for insomnia adapted for SWD (BT-SWD).

Methods

Forty-three night shift workers meeting SWD criteria were recruited (mean age = 34 years old; 77% women) and randomized to either BT-SWD or waiting list control group. Eight participants dropped-out while waiting. Before and after treatment, participants completed questionnaires (ESS, ISI, STAI and BDI-II) and sleep diaries throughout the experimentation. BT-SWD involves sleep restriction therapy and stimulus control for insomnia as well as fixed sleep periods in the dark for shift workers. BT-SWD has been applied to night sleep, day sleep, and naps in this order. It consists of 6 sessions of 50 minutes delivered on 8 weeks. A mixed MANOVA was conducted on questionnaires scores with group (treatment or waitlist) as the between-subject factor and time as the within subject factor.

Results

A multivariate interaction effect was significant, F(6,21) = 8.24, p<.001. A univariate interaction effect was observed for the BDI-II (p=.042), the trait scale of the STAI (p=.021) and the ISI, both for night sleep (p=.027) and day sleep (p<.001), indicating that the scores of participants in the treatement group lowered significantly more than those of participants on the waiting group. The treatment group had a significantly less severe insomnia, both for day sleep during night work (p<.001), and night sleep during days off (p<.001). There was no significant difference between the control and the treatment group on sleepiness levels.

Conclusion

BT-SWD is effective at reducing insomnia severity as well as levels of trait anxiety and depression. Results are more equivocal for sleepiness. The waiting list control group design used has led to an important attrition in the context of shift work. Further analyses are needed to determine the BT-SWD efficacy on sleep variables.

Support (if any)

The study was supported by a CIHR grant (#110254) awarded to the first author
521 Prevalence and Impact of Restless Legs in Patients with Myasthenia Gravis
Authors: AlGaeed Mohanad , McPherson Tarrant , Lee Ikjae , Feese Michelle , Aban Inmaculada , Cutter Gary , Kaminski Henry , Karroum Elias
Published: May 2021

Introduction

Restless legs syndrome (RLS) is a sensori-motor disorder characterized by an urge to move the limbs during inactivity alleviated at least partially by walking/stretching. By contrast, myasthenia gravis (MG) is a neuromuscular disease with fluctuating weakness aggravated by continued muscle activity. Only a few studies addressed the prevalence of RLS in MG patients with limitations related to small sample size and/or usage of non-validated RLS screening tools. The aim of this study was to revisit the prevalence and impact of RLS in a large sample of MG patients using the validated 13-item short-form Cambridge-Hopkins diagnostic questionnaire for RLS (CH-RLSq13).

Methods

The MG foundation of America patient registry was used to survey MG patients. Only patients aged ≥18 years, residing in the USA, and who answered “yes” to the question “Has your doctor diagnosed you with MG?” were included in this study. A survey including the CH-RLSq13, demographic information, disease related history, and patient reported outcomes including the MG15-item Quality of Life (MG-QOL15) and the MG-Activities of Daily Living (MG-ADL) instruments was sent to MG registry participants as part of the semi-annual follow up.

Results

A total of 630 MG patients (age: 62.8±13.2; 54.9% Women; 94.6% White) completed the survey and met eligibility criteria (22% of patients receiving the survey). The prevalence of RLS was 14.8% (93/630). Clinically significant RLS (moderately/extremely distressing RLS ≥2–3 days/week) was present in 53 (8.4%) MG patients. MG patients with (versus without) RLS were significantly younger (p=0.0061), more women (p=0.0440), with higher (worse) depression (p<0.0001), MG-ADL (p=0.0001), and MG-QOL15 (p<0.0001) scores.

Conclusion

Clinically significant RLS is prevalent in MG patients and is associated with a negative impact on mood, daily activities, and quality of life. Therefore, from a clinical practice it seems warranted to screen for RLS in MG patients.

Support (if any)

This study was not funded.