bluuebunny/crossref_metadata_2025 huggingface dataset:
0357 Interdisciplinary Training in Pediatric Sleep
Authors: Moore Melisa , Afolabi-Brown Olufunke , Tapia Ignacio , Beck Suzanne , Xanthopoulos Melissa , Mindell Jodi
Published: May 2022

Introduction

Sleep is a critical domain of child functioning. However, clinical psychology programs lack formal sleep education while behavioral sleep instruction is deficient in sleep and pulmonary fellowships. Cross-disciplinary training in pediatric sleep is ideal. This study examined medical and psychology trainee satisfaction with two interdisciplinary experiences: a 1-2 semester clinical rotation for medical fellows and psychology doctoral students and a concentrated annual elective for medical students. The rotation includes 1-2 half-day clinics per week wherein medical sleep fellows and behavioral sleep medicine trainees conduct a sleep interview together and ask specific questions within their discipline. With an attending psychologist and physician, they discuss case conceptualization, differential diagnoses, and possible interventions. The team reviews pertinent findings and collaboratively provides recommendations to the patient. Trainees also participate in weekly didactics presented by psychologists and physicians.The second interdisciplinary training experience, Frontiers, is designed to impact physician learners earlier in their careers. Sleep physicians and psychologists teach an annual week-long sleep elective for medical students.

Methods

Evaluations from fellows, psychology trainees, and medical students from the most recent 3 years were analyzed to determine trainee satisfaction with the interdisciplinary rotation and the medical student course.

Results

Results of sleep fellow evaluations rated the program as having effective teachers`X=4.67 (0.62) and high educational value `X=4.6 (0.83) on a 5-point Likert scale with 5 being the highest. Similarly, psychology trainees rated the overall rotation experience over the past 3 years on a 4-point Likert scale with 4 being the highest as`X=3.74 (0.43).Medical students who took the Frontiers course also rated the training highly on a 4-point Likert scale with 4 being the highest:`X=3.79 (0.43) in 2021,`X=3.76 (0.75) in 2019, and,`X= 3.73 (0.47) in 2018. The course was not offered in 2020 due to the pandemic.

Conclusion

Comprehensive pediatric sleep education and training (both clinical and didactic) is feasible within a single interdisciplinary rotation provided simultaneously to both psychology and medical trainees with high trainee satisfaction. Sleep-related in vivo training and didactics are relevant to physician and psychology training programs and prepare trainees for future work in interdisciplinary care.

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0362 The Cost of In-Person versus Telehealth PAP Initiation for Patients with Sleep Apnea
Authors: Jambulingam Nikita , Sarmiento Kathleen , Gomez Alexander , Smith Connor , Mitchell Michael , Lee Diane , Sanders Elizabeth , Ryden Armand , Martin Jennifer , Zeidler Michelle
Published: May 2022

Introduction

Telehealth has been widely integrated into healthcare systems during the COVID-19 pandemic and is likely to remain a part of routine clinical care. At the VA Greater Los Angeles Healthcare System (VAGLAHS), positive airway pressure (PAP) set-up visits transitioned from in person to telehealth for newly diagnosed sleep apnea patients during the pandemic. The telehealth pathway included mailing of PAP machines to patients with follow-up video/phone education by respiratory therapists (RTs). As part of a larger study examining the clinical outcomes resulting from telehealth versus in-person PAP initiation, we performed a cost analysis of these two treatment pathways within VAGLAHS.

Methods

We examined the total variable direct cost of telehealth versus in-person PAP initiation for patients newly diagnosed with sleep apnea at VAGLAHS between March and October 2021 (n = 2,662 PAP set-ups) using a bottom-up analysis. There was an average of 16 PAP set-ups per day with 11 set-ups (68.7%) via telehealth and 5 set-ups (31.3%) in person.

Results

The total variable direct cost of telehealth PAP initiation was $98.87 per patient. The total variable direct cost of in-person PAP initiation was $50.58 per patient. For telehealth, there was an additional cost of mailing the PAP machine and 31.2% more RT time spent on educating patients compared to the in-person pathway. After the initial PAP set-up visit, a larger subset of patients required additional troubleshooting help from RTs about proper PAP use after telehealth compared to in-person set-ups (5% versus 1%).

Conclusion

The telehealth PAP initiation pathway was nearly two times the cost of in-person PAP initiation. This resulted from the additional cost of mailing the PAP machine, more RT time spent on education, and a greater need for troubleshooting after the visit. Telehealth visits may need to be supplemented by written educational materials or web-based resources to reduce the need for additional support after the initial visit.

Support (If Any)

OCC study funding, VAGLAHS GRECC
0366 Investigating the use of STOP-BANG questionnaire in inpatient and outpatient settings in a rural healthcare system
Authors: Mojarrab Javad Najjar , Nwaedozie Somto , Stoflet Matthew , Yeung Paul , Kumar Sanjay , Biswas Amit
Published: May 2022

Introduction

Obstructive Sleep Apnea (OSA) is one of the strongest modifiable risk factors for Atrial Fibrillation (AF). Although, STOP-BANG questionnaire is a well-validated screening tool for OSA, its adoption and utility to screen newly diagnosed AF has not been reported in a large rural healthcare system. Our aim was to identify the characteristics in patients with AF, which led to screening and referral for a sleep study by providers. In addition, we identified the provider specialty types that had the highest rate of screening for OSA and sleep study referral.

Methods

We conducted a retrospective multicenter study that identified newly diagnosed patients with AF from January 2018- January 2020. STOP-BANG questionnaire, patient demographics, electrocardiogram, and sleep study data were collected. A logistic regression model was used to identify patient characteristics that were associated with increased screening. Using a chi-squared test, we compared differences in provider specialty that screened for OSA and referred patients for a sleep study.

Results

Among the study cohort (N=845), 136 (16.1 %) were female and 709 (83.9 %) were male. Only 82 patients (9.7%) had confirmed OSA screening by STOP-BANG questionnaire. Among higher risk patients for OSA (at least 3 of the following: age>50, male, hypertension, BMI>35), the screened patients were 5.8 years younger (95% CI: 3.7-7.9, p<0.001) compared to patients that were not screened. Patients who were screened for OSA had significantly higher BMI (p<0.001), hypertension (p<0.001), and diabetes mellitus (p<0.001). Our findings revealed that OSA screening providers, were most commonly Primary Care Providers (PCP) (47.5%) followed by cardiologists (31.7). Furthermore, PCPs (48.5 %) and cardiologists (14.1%) were most likely to provide referrals for a sleep study. All of the patients, who were screened using STOP-BANG questionnaire and referred for a sleep study, were diagnosed with OSA.

Conclusion

Our findings revealed underutilization of STOP-BANG to screen for OSA in newly diagnosed AF patients. Screening pattern may be tilted towards patients with obvious and severe forms of OSA therefore missing on milder cases. This study could prompt systemic adoption of STOP-BANG questionnaire, education, and periodic evaluation of healthcare providers in a large rural healthcare system to improve outcomes in AF patients.

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0370 Polysomnography following an indeterminate HSAT: Low Compliance with AASM Guidelines
Authors: Nygate Yoav , Rusk Sam , Turkington Fred , Fernandez Chris , Glattard Nick , Sprague Matt , Winzurk Zac , Watson Nathaniel
Published: May 2022

Introduction

Home sleep apnea test (HSAT) provides a low risk, cost-effective, and convenient diagnostic test for obstructive sleep apnea (OSA) in adult patients. However, in situations where HSAT are inconclusive, technically inadequate, or produce a negative result, the American Academy of Sleep Medicine (AASM) strongly recommends that a polysomnography (PSG) be performed. In this study, we evaluate whether patients are likely to comply with receiving a follow-up PSG following an indeterminate HSAT to rule out any presence of OSA and assess the demographic characteristics of individuals who are more likely to follow the AASM guidelines.

Methods

In order to assess routine compliance with the AASM follow-up guidelines, we have conducted an observational study with N=3,049 patients that received a HSAT in 2019 from 6 independent AASM accredited sleep centers across the U.S. The patient sample included 39.8% female and 60.2% male. 30.34% from the 19-44 age group, 47.2% from the 45-64 age group, and 21.2% from the 65-84 age group. Furthermore, 33% of the patients received a negative HSAT and were advised for a follow-up PSG.

Results

14.8% of patients who received a negative HSAT in 2019 underwent a follow-up PSG by the end of 2021. Male patients and patients who are younger in age were more likely to follow the AASM guidelines. 16.4% of male patients and 9% of female patients who received a negative HSAT underwent a follow-up PSG. 17.7% of patients aged 19-44 who received a negative HSAT received a follow-up PSG, while only 11.1% of patients aged 45-64, and 7.6% of patients aged 65-84 conformed with the AASM guidelines and followed-up with a PSG.

Conclusion

The overall percentage of patients who comply with the AASM guidelines is relatively low at 14.8%. Emphasis should be put on patient outreach and education to improve this statistic. Such endeavors may try to target female and older patients who appear to be slightly less compliant with AASM guidelines. Simultaneously, more attempts should be made to improve HSAT to increase OSA specificity and decrease the necessity for a follow-up PSG, as this AASM guideline is often overlooked by patients.

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0371 Sleep Medicine Care Through the COVID-19 Pandemic
Authors: Junna Mithri , Glasgow Amy , Sangaralingham Lindsey , Morgenthaler Timothy
Published: May 2022

Introduction

The COVID-19 pandemic accelerated use of telehealth, an expansion of services that required the appropriate technological infrastructure for health care facilities and in patient homes. Telehealth on the one hand has held promise for addressing health disparities perpetuated by inadequate rural access, but delivery requires extensive broadband and technologic access. That creates the possibility for new kinds of healthcare disparities. In addition, COVID-19 forced marked reduction in in-lab polysomnography (PSG), and concurrent expansion of home sleep apnea testing (HSAT). We hypothesized that the pandemic led to an increase in the overall frequency of telehealth and HSAT utilization, particularly in those who were younger, White, more educated, and from a non-local area.

Methods

We completed a retrospective chart review of all adult patients seen by all provider types across the Sleep Medicine practices in Mayo Clinic Rochester, Arizona, Florida, and the Mayo Clinic Health System between 1) 6/1/18—3/8/20 (Pre-COVID-19), 2) 3/9/20—4/19/20 (Early COVID-19), and 3) 4/20/20—present (Late COVID-19). We recorded the total number of PSGs and HSATs and total number of face-to-face and telehealth visits, along with the age, gender, race, educational level, and locality by zip code for patients served. These data were compared across the 3 timeframes.

Results

Average monthly visits changed from Pre-COVID-19, Early COVID-19, to Late COVID-19 [2194.7/m, 1416.5/m, 2690.6/m (P<0.001)]. Average monthly sleep test volumes also changed [1004.1/m, 530.5/m, 1123.4/m (P<0.001)], with a proportionate increase in HSATs across the 3 periods [34.71%, 65.37%, 53.59% (P<0.005)]. The increase in Late COVID-19 in telehealth visits occurred proportionately more in those who were younger, female, non-White, college and post-graduate educated, and from a non-local area. The increase in use of HSATs occurred proportionately more in patients who were younger, female, non-White, college and post-graduate educated, and from a local area.

Conclusion

The COVID-19 pandemic increased the use of telehealth visits and HSATs in Sleep Medicine practices across our enterprise, particularly in those who are younger and more educated, which may be due to ease of use with and access to technology. The reasons for the presence of additional disparities based upon gender, race, and locality needs further exploration.

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0384 Clinical Utilization of a CSF Orexin Test: First Two Years of Data from Mayo Clinic
Authors: Ruoff Chad , Louis Erick St , Cheung Joseph , Carvalho Diego , Larson Bethany , Silber Michael , Kotagal Suresh , Krahn Lois , Bornhorst Joshua
Published: May 2022

Introduction

Orexin deficiency in cerebrospinal fluid (CSF) was first reported in human narcolepsy in 2001, included in diagnostic criteria for narcolepsy in 2014, and made clinically available at the Mayo Clinic in 2019. The purpose of this publication is to report orexin test utilization and results, and other clinically relevant findings from patients evaluated at Mayo Clinic.

Methods

We retrospectively reviewed CSF orexin samples and clinical records from patients evaluated at Mayo Clinic from 2019 to 2021.

Results

A total of 98 internal samples (Rochester, n=56; Arizona, n=25, and Florida, n=17) from 95 patients (mean age 32.4 +/- 16.6 years with 20 %, 52 %, and 28 % of patients < 18, 18 – 40, and > 40 years, respectively, at time of CSF collection; 62 % female) have been submitted for CSF orexin measurement (mean CSF orexin 335.17 +/- 158.3 pg/ml; deficient < 110 pg/ml, n=11, 64 % <=40 years with mean age 32.9 +/- 17.0 years; intermediate 110 – 200 pg/ml, n=8, 100 % <= 40 years with mean age 21.1 +/- 12.8 years; normal > 200 pg/ml, n=79, 57 % <=40 years with mean age 33.5 +/- 16.7). No significant correlation was found between orexin levels, and time of collection (i.e., diurnal variation), gender, or age. Repeat testing was performed on three individuals (ages 10, 14, and 19 years) with a change in category of orexin level found in one patient from an intermediate to a normal level.

Conclusion

Orexin deficiency was found in 12 % of the patients (64 % of the deficient samples were found at ages <= 40 years). This result may reflect the fact that this test is frequently pursued in clinical patients presenting with inconclusive findings and/or comorbidities. Intermediate orexin levels found in 8 % of the samples (100 % <= 40 years). Although most of the patients tested were female (62.2%) and most were 40 years or younger (72%), no significant correlation was found between orexin levels, and time of collection (i.e., diurnal variation), gender, or age.

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none
0389 Efficacy of Lower-Sodium Oxybate in the Treatment of Idiopathic Hypersomnia: Evaluation of Response Based on the Epworth Sleepiness Scale Score
Authors: Rosenberg Russell , Chen Abby , Steininger Teresa , Macfadden Wayne , Dauvilliers Yves
Published: May 2022

Introduction

Idiopathic hypersomnia is a debilitating neurologic sleep disorder characterized by excessive daytime sleepiness (EDS), with sleep inertia and prolonged nighttime sleep as key symptoms in many patients. The Epworth Sleepiness Scale (ESS) is an 8-item self-report questionnaire (0–24 score range; higher scores indicate greater EDS). An ESS total score ≤10 is considered normal. The minimum clinically important difference (MCID) for narcolepsy is considered to be a decrease of ≥2 points; the MCID in idiopathic hypersomnia has not been established. This post hoc analysis evaluated response to lower-sodium oxybate (LXB; Xywav®) treatment on ESS scores in a phase 3 clinical trial (NCT03533114).

Methods

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

Results

Participants were treatment naive (n=47) or taking alerting agents other than sodium oxybate at study entry (stable doses ≥2 months; n=62). At W1, W4, W8, end of OLT, and end of SDP, the percentage of participants achieving a response of total ESS score ≤10 was 13.0%, 55.3%, 70.2%, 85.1%, and 87.2% (treatment-naive participants), respectively, and 21.0%, 56.5%, 65.6%, 74.2%, and 83.9% (participants taking alerting agents), respectively. At W1, W4, W8, end of OLT, and end of SDP, the percentage of participants achieving a response of total ESS score decrease of ≥4 points was 26.1%, 68.1%, 76.6%, 87.2%, and 87.2% (treatment-naive participants), respectively, and 33.9%, 64.5%, 78.7%, 88.7%, and 95.2% (participants taking alerting agents), respectively. Treatment-emergent adverse events (≥10%) included nausea, headache, dizziness, anxiety, and vomiting.

Conclusion

Over 80% of participants achieved a clinically meaningful response based upon ESS total score ≤10, and up to 95% demonstrated a decrease in total ESS score of ≥4 points at end of SDP. The response rate increased over the study period. The safety profile of LXB was consistent with that observed in narcolepsy.

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

Introduction

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

Methods

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

Results

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

Conclusion

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

Support (If Any)

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

Introduction

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

Methods

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

Results

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

Conclusion

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

Support (If Any)

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

Introduction

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

Methods

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

Results

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

Conclusion

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

Support (If Any)

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

Introduction

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

Methods

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

Results

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

Conclusion

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

Support (If Any)

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

Introduction

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

Methods

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

Results

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

Conclusion

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

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

Introduction

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

Methods

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

Results

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

Conclusion

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

Support (If Any)

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

Introduction

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

Methods

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

Results

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

Conclusion

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

Support (If Any)

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

Introduction

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

Methods

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

Results

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

Conclusion

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

Support (If Any)

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

Introduction

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

Methods

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

Results

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

Conclusion

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

Support (If Any)
0453 Lemborexant Exposure Is Independent of Race
Authors: Rawal Sumit , Landry Ishani , Lalovic Bojan , Nakai Kenya , Kubota Naoki , Moline Margaret
Published: May 2022

Introduction

Some hypnotic treatments for insomnia require dosing consideration due to exposure differences based on patient characteristics. Lemborexant (LEM) is a dual orexin receptor antagonist approved in multiple countries for the treatment of adult insomnia. LEM is not associated with exposure differences based on sex, age, or BMI that impact dosing. The potential impact of race on exposure was determined in two stand-alone pharmacokinetic (PK) studies and by modeling data from studies comprising the LEM clinical development program, which included healthy subjects and insomnia patients.

Methods

Study 003 (NCT02039089) was a single-center, multiple-dose, randomized, double-blind, placebo-controlled, parallel-group study in healthy Japanese and White subjects. Study 014 (NCT04555733) was a phase 1, single center, open-label, single and multiple oral dose study in healthy Chinese subjects. Additionally, effect of race on LEM exposure was independently examined as part of a population PK analysis incorporating LEM data from 9 Phase 1 studies (n=407), and Studies 201 (NCT01995838; n=235), 303 (NCT02952820; n=726) and 304 (NCT02783729; n=524) (Lalovic et al., 2020). Plasma concentrations of LEM were quantified from plasma by validated liquid chromatography with tandem mass spectrometry. Adverse events (AE) were recorded.

Results

Exposure of LEM increased in an approximately dose-proportional manner across the dose range (2.5 mg to 25 mg) in studies 003 and 014. There were no significant exposure differences between Japanese and White subjects following single LEM10 administration on Day 1 in Study 003 (maximum concentration [Cmax] mean[SD], ng/mL: Japanese, 46.5[25.8]; White, 47.3[28.1]; area under the curve from time zero to 24h [AUC0-24] mean[SD], ng·h/mL: Japanese, 231[40.2]; White, 208[83.4]) or when comparing PK data from Chinese subjects in Study 014 following single dose administration on Day 1 (Cmax mean[SD], ng/mL: LEM5, 29.8[12.8]; LEM10, 56.2[16.9]; LEM25, 116[46.8]; AUC0-24 mean[SD], ng·h/mL: LEM5, 106[29.9]; LEM10, 205[35.6]; LEM25, 549[116]) to Japanese and White subjects in Study 003. These results are supported by the cross-study, population PK model-based analysis, indicating no significant clinical or statistical differences in LEM PK attributable to the intrinsic factor race.

Conclusion

LEM exposure is not significantly affected by race. Therefore, dosing of LEM can be consistent across patient populations from different racial groups.

Support (If Any)

Eisai Inc.
0454 Response to Lemborexant in Older Subjects with Insomnia Disorder and Comorbid Pain at Baseline
Authors: Kaplan Alan , Cheng Jocelyn , Suzuki Masahiro , Kumar Dinesh , Malhotra Manoj , Moline Margaret , Pappadopulos Elizabeth
Published: May 2022

Introduction

The reciprocal relationship between pain and poor sleep has been well established. Pain interferes with sleep, and insomnia increases pain sensitivity, thus reducing quality of life. Therefore, it is of clinical importance to evaluate whether a sleep-promoting drug such as the dual orexin receptor antagonist, lemborexant (LEM; approved in multiple countries to treat adults with insomnia) can improve sleep in older patients, in whom both sleep and ongoing pain are prevalent.

Methods

Study 304 (NCT02783729), was a 1-month, double-blind, PBO- and active-controlled study in subjects age ≥55y with insomnia (full analysis set [FAS]=1006). Those who also endorsed some/severe pain at baseline on the pain/discomfort dimension of the EuroQual-5 Dimension-3 Level scale (EQ-5D-3L; no problems/some problems/extreme problems) at baseline were eligible for these post-hoc analyses. Medical history of pain conditions and/or ongoing therapy were not required for eligibility and were not evaluated. Subjects were randomized to bedtime doses of placebo, LEM 5mg (LEM5),10mg (LEM10) or zolpidem tartrate extended release (not reported here). Changes from baseline (CFB) in objective sleep parameters assessed by polysomnography (latency to persistent sleep [LPS]; wake after sleep onset [WASO]) were analyzed by mixed-effect repeated measures analyses adjusted for relevant factors.

Results

Approximately 18% of the FAS reported some or extreme pain at baseline (PBO=55; LEM5=78; LEM10=50). For LPS, baseline median values (minutes) were 31.0, 29.4 and 42.1 for PBO, LEM5 and LEM10, respectively. Median CFB for LPS were larger and statistically significantly different for both LEM doses compared with PBO at the beginning of treatment (mean of Nights 1/2: +2.5; -8.4, -15.8; P<0.005); and were (mean of Nights 29/30: -7.1,-9.9, -9.0) at the end of treatment LEM5 (P=0.031), LEM10 (P=0.054). For WASO, baseline median values (minutes) were 101.0, 103.6 and 111.1 for PBO, LEM5 and LEM10, respectively. Median CFB for WASO were larger and statistically significantly different (P<0.001) for both LEM doses compared with PBO at the beginning (Nights 1/2; -1.5; -41.5, -64.4) and end of treatment (Nights 29/30; -1.1, -37.9, -52.5).

Conclusion

These data suggest that lemborexant can effectively treat insomnia in older adults with concomitant painful conditions.

Support (If Any)

Eisai Inc.
0456 Comparative Safety and Efficacy of Hypnotics: A Quantitative Risk-Benefit Analysis
Authors: Cheung Janet , Scott Hannah , Muench Alexandria , Morales Knashawn , Grunstein Ronald , Krystal Andrew , Riemann Dieter , Perlis Michael
Published: May 2022

Introduction

Hypnotics continue to be preferentially used in practice for the treatment of chronic insomnia, yet the comparative safety and efficacy of medication options are unclear. While several position statements and network meta-analyses have provided some guidance, none have provided a quantitative assessment of risk-benefit. In the present analysis, each therapeutic class commonly used for chronic insomnia is quantitatively ranked with respect to safety, efficacy, and risk-benefit.

Methods

Safety data for FDA-approved hypnotics were extracted from the package insert adverse event tables and standardized to form a placebo-adjusted adverse event rate per 1000 (AEr). Efficacy data were extracted from randomized controlled trials identified in professional society position statements and published systematic reviews. The efficacy metric was computed from placebo adjusted pre-post change scores for self-reported sleep continuity (i.e., sleep latency [SL], wake after sleep onset [WASO], and total sleep time [TST]) and represented as a summed composite effect size score (SWT). Risk-benefit (R/B) was represented as a ratio between AEr and SWT. Comparative safety, efficacy, and risk-benefit metrics were calculated for five therapeutic classes: Benzodiazepines (BZs), non-benzodiazepine benzodiazepine receptor agonists (BZRAs), dual orexin receptor antagonists (DORAs), melatonin receptor agonists (MELAs), and sedating antidepressants (SADs).

Results

With respect to safety, MELAs had the lowest adverse event rate (AEr=43.1) and BZRAs had the highest rate (AEr=255.0). With respect to efficacy, BZs were the most efficacious (SWT=1.94, Mean ES=0.59) and MELAs were least efficacious (SWT=0.11, Mean ES=0.02). Overall, with respect to risk-benefit, SADs had the most favorable profile (R/B=69.5), while MELAs had the least favorable profile (R/B=395.7).

Conclusion

The optimal selection of hypnotics requires consideration of both risk and benefit. Findings suggest that SADs can be considered the first-line pharmacotherapeutic option due to the superior risk-benefit profile. If treatment responses are inadequate or if SADs are contraindicated, risk-benefit rankings may serve as a decision tree as part of a medical algorithm protocol to guide treatment selection for patients with chronic insomnia.

Support (If Any)

Sleep Research Society Mentor-Mentee Award (Cheung); K24AG055602 & R01AG054521 (Perlis)