Sleep Clinic Research Articles

0410 Utility of the Urine Drug Screen in Maintenance of Wakefulness Testing Interpretation - A Single-Center, Retrospective Analysis in Pediatric Patients

Abstract Introduction Accurate assessment of hypersomnia depends upon consideration of several factors, including use of medications that affect alertness and sleep organization. Urine drug screens (UDS) are recommended when assessing hypersomnia, but there is little standardization with respect to screening methods, types of substances detected, and use in maintenance of wakefulness test (MWT) interpretation, in part because there is scant literature relating UDS results to patients’ characteristics, MWT findings and implications. Methods A retrospective analysis was performed in adolescents evaluated at Cincinnati Children's Sleep Center between 2008 and 2021 who underwent MWT with concurrent UDS to determine the adequacy of hypersomnia treatment. UDS in our laboratory were performed by Qualitative Immunoassay/Gas Chromatography-Mass Spectrometry/Liquid Chromatography-Tandem Mass Spectrometry. Results A total of 109 MWTs were accompanied by UDS in 79 patients. Patients were 17.7 [16.6, 18.6] years old (median, [IQ range]), 41.3% female, 68.8% White, 25.7% Black, 5.5% Other, with a BMI of 25.8 [22.1, 31.8] kg/m2. 85.3% had narcolepsy. In addition to prescribed medications, caffeine was positive in 54.1% of UDS, and diphenhydramine was positive in 58.7%. No patients reported use of caffeine or diphenhydramine on the day of MWT. There were no significant demographic differences between those who tested positive and negative for caffeine. The median sleep latency in those with caffeine-positive UDS was longer than those with caffeine-negative UDS, although it did not reach statistical significance (27.3 [14.7, 38.3] vs 19.1 [9.8, 36.1] minutes; P=0.15). Patients with a positive UDS for diphenhydramine all took modafinil/armodafinil. In addition, 80% of patients taking modafinil/armodafinil had diphenhydramine-positive results. Nicotine and cannabinoids were detected in 2 UDS. Conclusion Two unexpected substances (caffeine and diphenhydramine) were found on UDS during MWTs in a significant proportion of our cohort. Caffeine may influence the results of MWTs, although further investigations are warranted. The unexpected presence of diphenhydramine is a false positive for those patients on modafinil/armodafinil (supported by literature and confirmed by our laboratory director). Sleep clinicians should be aware of these findings and the implications of unexpected substances when interpreting MWTs. Support (If Any) Cincinnati Children's Hospital Research Fund

0425 New onset insomnia following COVID-19 infection

IntroductionPost-COVID neuropsychiatric symptoms have a significant impact on morbidity following COVID-19 infection. We present three patients without a prior history of insomnia symptoms who developed new-onset and chronic insomnia following infection with COVID-19.MethodsRetrospective chart review was performed on three patients who presented to an ambulatory sleep clinic with complaints of new onset insomnia following COVID-19 infection.ResultsThree patients without a history of prior insomnia developed difficulty initiating or maintaining sleep during or following COVID-19 infection. Patient 1 developed symptoms of insomnia 2 weeks after recovery from COVID-19 infection. Symptoms improved after 5 months with a combination of hydroxyzine and cognitive behavioral therapy for insomnia (CBTi). Patient 2 developed insomnia at the same time as COVID-19 infection and symptoms consisted of sleep onset and maintenance insomnia.Hydroxyzine and trazodone were ineffective. Symptoms improved with zolpidem and CBTi. Patient 3 had a more severe course of COVID-19 infection requiring management in the intensive care unit that coincided with onset of insomnia. He presented to sleep clinic with new insomnia complaints but was also found to have moderate obstructive sleep apnea and periodic limb movements on polysomnography and prior history of restless legs. The patient was treated with a combination of positive airway pressure therapy and a dopamine agonist with plans to follow up to reassess severity of insomnia at future visit.ConclusionThree patients without a prior history of insomnia developed insomnia following infection with COVID-19. Management included a combination of CBTi and pharmacotherapy as well as treatment of underlying sleep disorders (OSA, RLS) when applicable. Further work is needed to understand the prevalence of new onset insomnia in patients following COVID-19 infection and best therapeutic approaches in this unique population.Support (If Any)

0703 Development of the Obstructive Sleep Apnea Questionnaire for Use in Clinical Practice

Abstract Introduction An American Academy of Sleep Medicine (AASM) task force identified a need for a valid, reliable, patient-reported outcome measure (PROM) to monitor obstructive sleep apnea (OSA) in adults in clinical practice. Ideally, the PROM should be easy and quick to complete (<5 minutes), available electronically, and accepted by clinicians treating OSA. Development of the Obstructive Sleep Apnea Questionnaire (OSA-Q) was undertaken to meet this need and was guided by the 2009 Food and Drug Administration (FDA) Guidance for Industry on developing PROMs. Methods Development of the OSA-Q included interviews with patients with OSA (n=14) to identify important concepts to them, conceptual model and draft questionnaire formulation, and cognitive interviews (n=14) to assess content validity and guide revisions to wording, item comprehension and redundancies, recall period, and response options. Usability of the electronic version of the OSA-Q was then assessed in patients with OSA. Finally, acceptability and utility of the OSA-Q in clinical practice was evaluated by surveying clinicians in ten geographically-dispersed US sleep clinics. Results Patient interviews were used to construct a conceptual model for the draft OSA-Q which served as a basis for generating 44 items about daytime/night-time symptoms and OSA impacts. Cognitive interviews identified poorly worded, ambiguous, and redundant items to inform revisions, resulting in a revised draft OSA-Q (3 domains, 28 items). Subsequently, clinicians (n=13) administered the draft OSA-Q to five patients each, obtained patients’ feedback on the OSA-Q, and completed a survey regarding its comprehensiveness, format/content, utility, and acceptability in clinical practice. These clinicians endorsed the OSA-Q for ease of use, language simplicity, convenience of electronic platform, and speed of completion (3-5 min). They also indicated that the OSA-Q would be useful in clinical practice and enhance patient communications (69% and 77%, respectively). The OSA-Q was revised and finalized for psychometric testing, based on clinician comments. Conclusion A new AASM-supported PROM to monitor OSA in clinical practice has been developed, including the patients’ perspective according to FDA guidance. This OSA-Q shows content validity and is positively perceived by clinicians. Psychometric testing of the OSA-Q is underway to establish its measurement properties and demonstrate its validity, reliability, and sensitivity to change in patients with OSA. Support (If Any) This work was funded by the American Academy of Sleep Medicine.

0319 Age Estimation from Sleep using Deep Learning Predicts Life Expectancy

Abstract Introduction Sleep disturbances increase with age and are predictors of mortality. However, summary metrics typically derived in sleep clinics from gold standard clinical analysis of polysomnograms (PSGs) only represent a very small fraction of data collected. In this study, we designed deep neural networks that estimate age as a proxy for overall health using full PSG signals. Age estimation was next used to evaluate association to mortality risk. Methods Aging was modeled using 2,500 PSGs and tested in 10,808 PSGs from men and women in 7 different cohorts aged between 20 and 90. The deep neural network was trained using as a regression model of age in the 2,500 PSGs roughly uniformly distributed across 6 to 90 years. The estimates of the network were interpreted using Gradient SHAP, which attributes relevance scores to the input in terms of the age estimate. The association between age estimate error (AEE), which is the residual of the estimate, and mortality risk was investigated with Cox proportional hazards models that adjusted for demographics, sleep, and health covariates. Results Ages were estimated with a mean absolute error of 5.81 ± 1.18 years, while a linear regression model using basic sleep scoring measures had an error of 15.10 ± 6.48 years. Interpretation of the network revealed that patterns such as arousal, sleep apnea, and sleep stage transitions contribute to the age estimate. Each 10-year increment in AEE was associated with increased all-cause mortality rate of 28 % (95% confidence interval: 19–38 %) and cardiovascular mortality rate of 38 % (95% confidence interval: 19 – 59 %). An increase from -10 to +10 years in AEE translates to an estimated decreased life expectancy of 6.21 years (95% confidence interval: 4.31–8.21 years). Conclusion Greater AEE was mostly reflected in increased sleep fragmentation, suggesting this is an important biomarker of future health independent of sleep apnea. Support (If Any) The Klarman Family Foundation and grants HL46380, M01 RR00080-39, T32-HL07567, RO1-46380, U01HL53916, U01HL53931, U01HL53934, U01HL53937, U01HL64360, U01HL53938, U01HL53940, U01HL53941, U01HL63463, 38-PM-07, R01HL62252, R01AG036838, R01AG058680, 1UL1RR025011, U01AG027810, U01AG042124, U01AG042139, U01AG042140, U01AG042143, U01AG042145, U01AG042168, U01AR066160, UL1TR000128, R01HL071194, R01HL070848, R01HL070847, R01HL070842, R01HL070841, R01HL070837, R01HL070838, R01HL070839, R24HL114473, and 75N92019R002.

0821 Narcolepsy after West Nile Virus Meningoencephalitis infection

Abstract Introduction Narcolepsy is a sleep disorder characterized by hypersomnia and inappropriate intrusion of REM sleep into wakefulness. Etiology is heterogeneous, and is broadly classified into Narcolepsy Type 1 and Type 2. There is growing evidence that the pathogenesis in many cases have a post-infectious autoimmune basis. We present the case of a patient seen in our sleep clinic who was eventually diagnosed with Narcolepsy type 2 following West Nile Virus (WNV) Meningoencephalitis. Report of Cases: · The patient is a 44 year old Hispanic woman who had no prior sleep difficulties before 2013, when she was diagnosed with WNV meningitis. Lumbar puncture results from the time of infection are not available, as this evaluation occurred in the Dominican Republic. Subsequent lumbar punctures have shown the presence of anti-WNV IgG antibodies in her CSF. MRI and MRA brain were unremarkable. · She also has a history of migraine, fibromyalgia, depression, and adrenal insufficiency. · She presented with sleep complaints, including sleep onset insomnia, symptoms of sleep disordered breathing, and excessive daytime sleepiness. · She underwent home sleep apnea test in 12/2020 which revealed mild obstructive sleep apnea. Overall AHI was 7.9/hour without significant hypoxemia. She was subsequently started on CPAP therapy with good adherence, but she continued to have significant daytime sleepiness, notably with an Epworth Sleepiness Scale score of 21/24. · She subsequently underwent overnight polysomnogram and multiple sleep latency test in our sleep laboratory. · Overnight PSG confirmed mild obstructive sleep apnea (AHI 12.0) along with short REM latency (10.5 minutes). Next day MSLT showed mean sleep latency of 2.3 minutes, for 5 attended naps, with 2 SOREMPs, which was diagnostic of Narcolepsy type 2. Conclusion This case demonstrates the onset of narcolepsy after WNV meningoencephalitis. Support (If Any)

0525 The Effects of the COVID-19 Pandemic on Continuous Positive Airway Pressure (CPAP) Adherence in Pediatric Patients with Obstructive Sleep Apnea (OSA)

Abstract Introduction CPAP Adherence in children with OSA is often sub-optimal and there is concern for worsening during the COVID-19 pandemic. Although telehealth has been used in sleep clinics during the pandemic, there is little known about telemedicine’s effectiveness in specialized care. The purpose of this study is to compare CPAP adherence and related outcome metrics in pediatric OSA patients seen before and during the COVID-19 pandemic and between those seen in person and by telemedicine. Methods This retrospective cohort consisted of patients who were diagnosed with OSA, prescribed CPAP, and were seen in a CPAP clinic between 1/1/2018 and 9/31/2021. CPAP adherence data and outcome metrics including the Epworth Sleepiness Scale (ESS), Michigan Sleep-disordered Breathing (PSQ) and Pediatric Quality of Life questionnaires (Ped-QOL) were collected. Only patients with one pre-pandemic and at least one post-pandemic visit were included. All variables were reported as mean± SD. Statistical comparison was performed using the mixed-effects model. Results 147 patients met criteria with 353 total visits. 147 were before the pandemic (pre) and 206 were during the pandemic (post). Demographic data indicated 57% male, 82% white, and 63% 12 years and older. Post-pandemic visits consisted of 78% telemedicine. Comparison between pre and post pandemic data demonstrated no statistically significant differences in % CPAP usage>4hrs (71±31% [pre] vs 73±33% [post], p=0.95), ESS (6.4±5.5 [pre] vs 5.9±5.8 [post], p=0.27), or PSQ (0.38±0.22 [pre] vs 0.36±0.22 [post] p=0.90). However, there was a significant difference in Psychosocial Health domain of Ped-QOL (68.6±19.4 [pre] vs 74.5±17.9 [post], p=0.012). Comparison between telemedicine and in-person visits during the pandemic showed no differences in %CPAP usage>4hrs (73±31% [Tele] vs 73±37%, p=0.73), ESS, PSQ, or Ped-QOL. Conclusion In our cohort, children with OSA had no significant changes in CPAP adherence, sleepiness, or OSA symptoms during the COVID-19 pandemic. CPAP telehealth visits provided the same effectiveness as in-person visits, as evidenced by similar adherences and outcome metrics. Interestingly, patients reported higher psychosocial health during the pandemic despite no difference in CPAP adherence. Factors not related to OSA management may contribute to the improvement of quality of life in this population. Support (If Any) Cincinnati Children’s Research Fund

0767 Clinical implementation of a program to improve PAP acceptance and adherence for sleep disordered breathing among Veterans: Preliminary results

Abstract Introduction Positive airway pressure (PAP) is the gold standard in treating sleep disordered breathing (SDB); however, consistent use of this therapy has challenges such as comfort and equipment optimization. Despite various educational, technological, psychosocial and pharmacological strategies, the average adherence rate of 34% have changed very little over the past 20 years. A recent study of 3013 US veterans determined a baseline average PAP adherence rate of 50%. We developed and implemented a novel PAP readiness education program (PREP) for veterans newly diagnosed with SDB in a Veterans Administration sleep clinic to promote greater PAP acceptance and adherence. Methods Patients (N=63, Mean age 62.2±12.4 years) with newly diagnosed SDB were offered a 1-hour telehealth session prior to initiating PAP therapy that included psychoeducation about SDB and PAP treatment expectations, with troubleshooting techniques (i.e. scheduled practice, mindfulness). A 1-week follow-up call was conducted to communicate PAP data and address treatment barriers. PAP use reports were downloaded and analyzed at 1-7 days (first week), 1-30 days (first month), and 31-60 days (60-days) post-PAP initiation. PAP acceptance was defined as ≥1 day of use and adherence as ≥4 hours of use at each timepoint. Results Among 63 Veterans offered PREP, 66.6% (n=42) participated in PREP. Among participants, acceptance of PAP was as follows: 57.1% used ≥1 day in the first week, 64.3% used ≥1 day in the first month, and 45.2% used ≥1 day at 60-days post-PAP initiation. Percent of days with use ≥4 hours was 28.9% ±30.4 in the first week and 24.9% ±30.0 in the first month. PAP adherence at 60-days post-PAP initiation was 34.3% ±38.5 at 60-days. Conclusion Implementation of a 1-session plus 1-week follow-up call PAP readiness education program within a sleep medicine clinic was well received by patients and resulted in PAP acceptance by 2/3 of veterans in the first month post-PAP initiation. PAP adherence results may have reflected the impact of a nationwide PAP device recall that occurred during the study period. Further work is needed to test this intervention in a clinical population and to identify predictors of PAP acceptance and adherence in real-world clinical settings. Support (If Any) AASM Foundation #211-FP-19, VAGLAHS GRECC and CSHIIP

0082 External Validation of an Enhanced Machine Learning Algorithm: Polysomnography-Based Narcolepsy-Like Feature Assessment and Clinician Notification in Routine Sleep Medicine Clinics

Abstract Introduction Polysomnography (PSG) contains quantitative information that, using machine learning (ML) algorithms, may aid the identification of type 1 narcolepsy. This study aimed to evaluate the utility of a previously developed quantitative tool (ML evaluation of PSG data) for detecting narcolepsy (types 1 and 2) in a “real-world” sleep clinic population. Methods Nocturnal PSG studies from a random sample of sleep clinic patients (narcolepsy, n=302; controls, n=21,535) were randomly split (1:1) into a training set and a validation set for algorithm testing. A separate, external PSG dataset was used for additional testing of the final model. Sleep stage probability graphs (hypnodensities) were estimated from PSGs on 15-second epochs using a previously developed convolutional neural network. Feature engineering was applied to hypnodensities to create a feature vector that was used to train a Gaussian process (GP) model to identify patients with a high probability of having narcolepsy. Features could be scaled to the 85th percentile, zero-mean and unit-variance, or unscaled. A recursive feature-elimination scheme was compared with training the GP kernel’s length scale for determining the subset of features that best discriminate narcolepsy and controls. A synthetic minority oversampling technique was applied in combination with random undersampling to balance the distribution of cases and controls in the training set. Several kernels and relevant hyperparameters were evaluated. Model performance (specificity and sensitivity) was examined using receiver operating characteristics with the goal of achieving an area under the curve (AUC) ≥0.80. Results The final GP model used a Matérn 5/2 covariance kernel with the length scale hyperparameter trained to determine the feature subset selection. Input features were normalized to zero-mean and unit-variance. The model had AUC=0.9960 and AUC=0.8014 for classifying narcolepsy in the training and validation sets, respectively. Sensitivity ranged from 73% to 65% when specificity was between 75% and 80%. Final performance evaluation of the model for classifying narcolepsy in an external PSG dataset is ongoing; results will be presented at the congress. Conclusion An ML-based algorithm can offer an objective, sensitive, and specific tool for alerting sleep clinicians about patients at risk for narcolepsy, using nocturnal PSG in general sleep medicine clinics. Support (If Any) Jazz Pharmaceuticals.

0844 Isolated, Idiopathic Periodic Breathing in a School Age Child

Abstract Introduction Periodic breathing (PB) is a well described physiologic phenomenon of infancy and usually resolves with age1. PB that persists outside of infancy has been described in association with various pathologies such as Chiari malformation, upper airway anomalies and genetic abnormalities2. Isolated PB that persists past infancy is less well described, and there is little data to guide subsequent management and clinical decision making. Report of Cases: Here we present a case of a 12-year-old female with isolated PB on polysomnography (PSG). She initially presented to our sleep center clinic with complaints of snoring, gasping during sleep and daytime sleepiness. She had no significant past medical history and not on any sleep-modifying medications. PSG was ordered to evaluate for suspected obstructive sleep apnea. Total sleep time was 7.75 hours with a mildly reduced amount of REM (16% of total sleep time). She had a total of 4 minutes of central sleep apnea that met AASM criteria for periodic breathing. This occurred exclusively during transitions between N1 and N2 and was not associated with hypoxemia nor hypocapnia. The patient’s total apnea hypopnea index (AHI) was 2.97/hr, obstructive AHI 0.65/hr and central apnea index was 2.32/hr. Of note, this studywas not conducted at high altitude and was done in Houston (approximately 100 feet above sea level). Given the lack of significant sleep apnea, a conservative approach with nasal fluticasone and close follow-up was utilized. Conclusion Though rare, this case highlights the possibility of PB being an incidental finding of PSG in otherwise healthy, school aged children. The need for further research as to the significance of this incidental finding is also emphasized. Support (If Any) 1. MacLean, Joanna E., Dominic A. Fitzgerald, and Karen A. Waters. "Developmental changes in sleep and breathing across infancy and childhood." Paediatric respiratory reviews 16.4 (2015): 276-284.2. Ghirardo, Sergio, et al. "Central apnea and periodic breathing in children with underlying conditions." Journal of Sleep Research (2021): e13388.

0605 Longitudinal assessment of CPAP use in Sleep Medicine Clinic Patients during the COVID-19 Pandemic

Abstract Introduction Due to the COVID-19 pandemic, there may be changes in continuous positive airway pressure (CPAP) adherence. This study aimed to examine the longitudinal effect of using CPAP as advised and self-reported sleep quality improvements in sleep medicine clinic patients using CPAP early in the pandemic and six months later. Methods Between June-November 2020, 81 sleep medicine clinic patients completed an online survey that included questions about CPAP use, using CPAP as advised, and changes in sleep quality associated with CPAP use. Patients were recontacted 6 months later to complete the same survey. Among survey respondents completing both surveys, 27 (50%; aged 58±18.2 y, 48% female, 67% Caucasian) reported using CPAP and were included in the present analysis. We conducted multivariate regression analyses Chi-square Association tests to determine whether self-reported CPAP use, CPAP use as advised, and sleep quality changed from baseline to 6-month follow up during the pandemic. Results Among CPAP users, 89% reported no change, 7% reported they use CPAP more, and 4% reported they use CPAP less at 6-month follow up. There was a significant increase in using CPAP as advised at 6-month follow up compared to the baseline survey, p=0.003. Additionally, there was a significant improvement self-reported sleep quality while using CPAP at 6-month follow up compared to the baseline survey, p=0.012. Conclusion Patients reported an increase in using CPAP advised and improvements in sleep quality as a result of CPAP use at 6-month follow up compared to a baseline survey administered early in the pandemic. Understanding why patients are more adherent to using CPAP as advised during the pandemic may help in developing interventions to increase CPAP adherence. Support (If Any) This work is supported by National Institutes of Health Grant # R01NR018342 (PI: Nowakowski) and by the Department of Veteran Affairs, Veterans Health Administration, Office of Research and Development, and the Center for Innovations in Quality, Effectiveness and Safety (CIN 13-413).

0604 Depression, Anxiety and Coping-avoidance Behaviors Associated with Long-Term Insomnia Symptoms During the COVID-19 Pandemic

Abstract Introduction Stressful events, such as the COVID-19 pandemic, can have long-lasting, detrimental effect on sleep. It is important for practitioners to understand how their patients may be stil experiencing residual negative effects of the pandemic to optimize their care. In this study we evaluated how measures of self-reported measures of anxiety and depression during the COVID-19 pandemic predicted measures of sleep disturbnce 6 months later among sleep medicine clinic patients. Methods Between June-November 2020, 81 sleep medicine clinic patients (54.8±15.9 y, 44% male, 69% Caucasian) completed an online survey that included PROMIS measures (Sleep Disturbance, Sleep-Related Impairments, Informational Support, Emotional Distress-Anxiety) and Insomnia Severity Index (ISI). Patients were recontacted 6 months later to complete the same surveys. 54 patients (55.2±18.4 y, 39% male, 70% Caucasian) completed the follow-up survey and were included in this present analysis. We conducted multivariate regression analyses to determine how the change in self-reported PROMIS measures from baseline during the pandemic were predictive of post-pandemc 6 month follow-up PROMIS measures and ISI. Results PROMIS depression score at baseline was predictive of both sleep disturbance (0.63 ± 0.15; p<.0001) and sleep impairment (0.49 ± 0.18; p=0.01) 6 months later. Baseline brief coping avoidance also predicted 6 month sleep disturbance (0.85 ± 0.33; p<0.009) and sleep impairment (0.85 ± 0.33; p=0.014) as well as ISI (0.52 ± 0.18 units; p=0.006). Baseline anxiety predicted ISI at 6 months (0.25 ± 0.09 units, p=0.009). Conclusion Higher levels of self-reported depression, anxiety and coping-avoidance behaviors during the COVID-19 pandemic lead to long-lasting increase in sleep disturbance and impairment as well as insomnia. Addressing depression, anxiety and coping behaviors that occur as result as a stressful event is advised to avoid long-term detrimental effects on sleep. Support (If Any) This work is supported by National Institutes of Health (NIH) Grant # R01NR018342 (PI: Nowakowski) and by the Department of Veteran Affairs, Veterans Health Administration, Office of Research and Development, and the Center for Innovations in Quality, Effectiveness and Safety (CIN 13-413).

0798 Detriggered - a case of tenosynovitis ameliorated by CPAP

Abstract Introduction The influence of sleep quality and pain is bidirectional (1). Sleep loss can induce hyperalgesia through upregulated inflammatory mediators such as IL-6 and TNF (2, 3). Obstructive sleep apnea (OSA) is characterized by obstructive respiratory events, hypoxemia, sleep fragmentation, and ultimately poor quality sleep. Here we present a case of how the treatment of OSA with continuous positive airway pressure (CPAP) mitigated hand inflammation and trigger finger symptoms. Report of Cases: A 60 year old male with prediabetes, hypertension, and BMI 30 presented to primary care with bilateral finger pain and stiffness. Hand orthopedics noted a tender left A1-pully 4th finger with 20 degree flexion contracture and a palpable right 3rd finger flexor tendon nodule causing definite triggering. He was diagnosed with trigger finger and initially treated with steroid injections and again 5 months later due to persistent symptoms. 10 months after the initial orthopedic visit, orthopedics planned for surgical intervention, but patient missed his surgery for unknown reasons. 7 months later, sleep medicine evaluated the patient for snoring and daytime fatigue. He underwent home sleep apnea testing which revealed a respiratory event index (REI) of 36.7 which necessitated CPAP therapy. Unfortunately, the patient was then lost to follow up in sleep medicine clinic. More than a year later, the patient showed to clinic and found to have 100% CPAP compliance with residual REI of 0.7. He enthusiastically noted improvement of daytime fatigue and trigger finger symptoms when using CPAP. When he would forget to use CPAP at night or during naps, he would wake up with returned finger pain and stiffness. Per patient, the symptoms would then resolve after re-initiation of CPAP. This consistent association of CPAP and finger symptom amelioration continued even 8 months later in most recent follow up. Conclusion To our knowledge, this is the first report of trigger finger symptoms improving with treatment of OSA. One hypothesis is that through improved sleep quality, there is a dampening of chondrocyte proliferation of the retinacular sheath and allowing unrestricted motion of the flexor tendon (4). More studies are needed to evaluate the musculoskeletal benefits of CPAP for OSA. Support (If Any) 1. Haack M. Scott Sutherlandj. Et al. Pain sensitivity and modulation in primary insomnia. Eur J Pain. 2012, 16: 522-533.2. Chhangani BS, Roehrs Ta et al. Pain sensitivity in sleepy pain-free normals. Sleep, 209, 32:1011-1017.3. Li, Joule Sarah Appleton. Association of Musculoskeletal Joint Pain with Obstructive Sleep Apena, Daytime Sleepiness, and Poor Sleep Quality in Men. Arthritis Care and Research Vol 69. No 5. May 2017.4. Makkouk Al Hasan et al. Trigger finger: etology, evaluation, and treatment. Curr Rev Musculoskeltal Med 2008. 1:92-96.

0657 Evening chronotype moderates the relationship between maternal and offspring’s depressive symptoms in a clinical population of adolescents

Abstract Introduction Although depression has shown a strong familial aggregation tendency, there are some moderators between parental and offspring’s depression. Meanwhile, it is known that evening chronotype is a risk factor for depression. Therefore, this study aimed to evaluate the moderating role of chronotype in the relationship between maternal and adolescent depressive symptoms in a clinical sample. Methods Seventy-five adolescents who visited a sleep or psychiatric clinic with a major complaint of sleep disturbance or emotional problems agreed to participate, 51 adolescents and at least one biological parent who completed questionnaires were included in the current analysis (17 male adolescents, aged 9-17 yrs). Adolescent’s chronotype were measured by the reduced Morningness-Eveningness Questionnaire (rMEQ). Depressive symptoms in adolescents and parents were assessed by the Depression Self-Rating Scale for Children (DSRSC) and the Patient Health Questionnaire (PHQ-9), respectively. General linear models were applied to examine the interaction between parental depression and adolescent’s chronotype on adolescent’s depression, in which age and gender were entered as covariates. Results Mothers of adolescents with clinical depression (DSRSC>15, n=38) also reported more depressive symptoms (PHQ-9: 4.81±4.37 vs. 2.69±2.46, t=-2.14, p=0.039). But father’s depressive symptoms were not related with adolescent’s depression. In the current clinical sample, the prevalence of evening chronotype in adolescents was up to 45.1% (n=23). Adolescents with either non-evening or evening chronotype reported comparable level of depressive symptoms (DSRSC: 20.37±6.26 vs. 19.00±8.42, t=0.66, p=0.513). There was a significant interaction between maternal depressive symptoms and chronotype on offspring’s depressive symptoms (F=4.05, p=0.044). Specifically, maternal depressive symptoms were associated with offspring’s depressive symptoms only in adolescents with evening chronotype. Conclusion Our study suggested that adolescents with evening chronotype might be at an elevated risk of the transgenerational transmission of depression. Hence, our findings supported the need to consider circadian factors and maternal depression in identifying at-risk adolescents. Support (If Any) This work was supported by the Shanghai Sailing Program awarded to Dr. Wanqi Sun (Shanghai Science and Technology Committee, 19YF1442200).

0746 Mediation of Biomarkers of Inflammation in Sleep-Related Hypoxia and COVID-19 Clinical Outcomes

IntroductionCentral to the pathophysiology of SARS-CoV-2 is immune dysregulation and systemic inflammation, however, it is yet unknown whether sleep-related hypoxemia--which we have recently noted to be associated with worse COVID-19 clinical outcomes--is mediated by these biomarkers and pathways.MethodsData from patients who tested positive for SARS-CoV-2 and part of the integrated Cleveland Clinic COVID-19 and sleep laboratory registries from March-November 2020 were included. To assess the mediation effect of biomarkers, the relationship between sleep-related hypoxia measures (% sleep time<90%SaO2,T90) and moderate/severe WHO-7 COVID-19 score (use of supplemental oxygen, non-invasive ventilation, mechanical ventilation/ECMO or death) was first tested. The mediation effect, or natural indirect effect, of biomarkers of inflammation (C-Reactive Protein (CRP), white blood cell (WBC) count (with a focus on lymphocyte count) and lactate) was then estimated by logistic regression models adjusted for demographics, comorbidities, smoking pack year and site location using PROC CAUSALMED statement in SAS software (version 9.4, Cary, NC).ResultsThe analytic sample included 446 patients hospitalized due to COVID-19: age:63.3.±13.8 years,51.3% female,39% African American with body mass index(BMI)=36.1±9.3kg/m2. Thirty-six percent used supplemental oxygen, 4% used high-flow or non-invasive ventilation,5% required ECMO or mechanical ventilation and 2% died. Hypoxic measures were associated with moderate/severe WHO-7 COVID-19 outcome: T90 median (>1.8%vs.≤1.8%) (OR=2.04, 95%CI:1.28-3.23,p=0.003), 5% increases in both mean SaO2 (OR=0.43, 95%CI: 0.26-0.70,p=<0.001) and minimum SaO2 (OR=0.84, 95%CI: 0.72-0.99,p=0.03). CRP was associated with mean SaO2 (p=0.040) and minimum SaO2 (p=0.029), likewise mediation analysis showed that there was a significant natural indirect effect of CRP in both hypoxia measures (OR=0.86,95%CI 0.73-0.99,p=0.036;OR=0.95,95%CI 0.90-1.00,p=0.034 respectively). WBC count, but not lymphocyte count subset, was associated with mean SaO2 (p=0.044), but the natural indirect effect was not significant (p=0.23. Lactate was associated with minimum SaO2 (p=0.044), but the natural indirect effect was not significant (p=0.23). T90 median was not associated with CRP(p=0.13), WBC count(p=0.87) or lactate(p=0.28).ConclusionCRP appears to represent a relevant mediator of sleep-related hypoxia and WHO-7 clinical outcomes. Further investigation is needed to elucidate if treatment of sleep-related hypoxia downregulates biomarkers of systemic inflammation to modify disease course.Support (If Any)

0823 ACDF - A hidden etiology of OSA

Abstract Introduction OSA is characterized by recurrent episodes of upper airway collapse and obstruction during sleep, leading to oxygen desaturations. Risk factors include obesity, age, sex, family history, craniofacial abnormalities, stroke, diabetes, polycystic ovarian syndrome. This case illustrates symptomatic and clinically proven worsening of OSA after anterior cervical discectomy and fusion (ACDF), which can lead to narrowing of the airspace and dysfunction of the pharyngeal plexus leading to upper airway collapse. Report of Cases: A 49-year-old female with cervical myelopathy was evaluated in the sleep clinic for snoring, witnessed apnea, and daytime somnolence. Her Epworth score was 11, and Mallampati score was 4, suggestive of underlying sleep-disordered breathing (SDB). A home diagnostic sleep test revealed mild OSA with AHI of 6.8/hr and was started on an Auto Continuous Positive Airway Pressure (APAP) device. She then reported worsening of her cervical pain leading to decreased use of APAP and total sleep time and underwent ACDF approximately 6 months after her diagnosis of OSA was made. Post-surgery she reported mild dysphagia, frequent nighttime awakening due to a choking sensation, and an increase in snoring. Following hospital discharge, the patient was re-evaluated in the sleep clinic for these complaints. Upon review, her BMI had decreased to 33.99 kg/m2, from 37.35 kg/m2, and the only medication change was the addition of hydrocodone-acetaminophen 5-325, 1-2 times daily as needed for pain. A repeat diagnostic home sleep study showed progression of OSA to moderate severity with an AHI of 24.5/hr, with no evidence of central sleep apnea or hypoventilation. Therefore, it was unlikely that the worsening of AHI was due to opioids. Thus, it was concluded that ACDF most likely led to the worsening of OSA. Conclusion Although there is no strong association in medical or sleep literature, this case demonstrates a strong association between ACDF and OSA. This highlights the importance of a timely diagnosis of new-onset or reassessment for worsening OSA in patients post-ACDF to improve sleep quality and prevent morbidity. Support (If Any)

0498 Intravenous Iron Therapy in the Pediatric Sleep Clinic: A Single Institution Experience

Abstract Introduction Initial reports of intravenous (IV) iron administration have been promising for children with restless legs syndrome (RLS), periodic limb movement disorder (PLMD), and restless sleep. The aim of the current study was to further evaluate the clinical response to IV iron supplementation in children seen in a pediatric sleep clinic. Methods We performed a retrospective chart review of children cared for in a single pediatric sleep clinic who also underwent IV iron infusion. Data regarding their sleep symptoms and ferritin levels were abstracted. Results Overall, 63 pediatric sleep patients underwent IV iron infusion, mostly with ferric carboxymaltose (n=60). Of the 59 patients with clinical follow-up, 39 (73%) noted improvement in at least one symptom, and 14 (26%) did not notice improvement or noticed worsening symptoms. Of the 59 patients with pre- and post-infusion labs, the average ferritin level increased from 21.7+/-13.3 to 147.9+/-120.9, p&amp;lt;0.001. Comparing patients who experienced clinical improvement versus those who did not, there were no statistically significant differences in change in ferritin levels (176.6+/-127.7 vs 120.5+/-118.1, p=0.278), sex (68% in females vs 77% in males, p=0.452), or age (8.8+/-5.9 vs 7.0+/-5.1, p=0.391). In terms of immediate adverse reactions to the IV infusion, 7 (11%) experienced at least 1 side effect, with the most common being behavior change (n=6) or gastrointestinal discomfort (n=4); no episodes of anaphylaxis or extravasation were noted. Conclusion These data provide additional support for the efficacy and safety of IV iron for pediatric RLS, PLMD, and restless sleep recalcitrant to oral iron. Support (If Any)

0483 Clinical Model of Community-Based Sleep Education Intervention for Children with IDD

Abstract Introduction Sleep difficulties are common for children with intellectual and developmental disabilities (IDD). We previously found that implementing the principles of community-based sleep education intervention with children with IDD through a consultative caregiver training model improved key components of sleep and was a feasible model for both providers and caregivers (MacDonald, 2021). Methods Record reviews were conducted from a behavioral sleep clinic for children with IDD to evaluate for the reported effectiveness of the recommendations provided on improving sleep and to gather information regarding reported caregiver implementation of recommendations. A clinical psychologist trained in community-based sleep education and IDD met with 43 children, ages 1 to 18 years old with clinical diagnosis of an IDD, and at least one caregiver, to give individualized recommendations for their caregiver-reported sleep issues. These patients were referred to the psychologist by a developmental medical provider or a sleep medical provider after medical evaluation of these concerns. Concerns consisted of sleep onset latency, nighttime wakings, and/or co-sleeping. Patients and caregivers typically met 1 to 3 months after the initial visit to report their success at implementing recommendations and to share if there were any improvements at first follow-up or questions/concerns regarding the recommendations or sleep behavior. In some cases, additional follow-up visits were typically scheduled 1 to 6 months after and these were also reviewed. The notes from these visits were evaluated using qualitative measures and tools modified from Pediatric Sleep and Autism Clinical Global Impressions Scale (Pediatric CGI; Malow, 2016) to determine effectiveness and feasibility. Results Qualitative and quantitative measures adapted from Pediatric CGI were used by the record reviewer to evaluate notes. It was observed that 86% of caregivers reported complying with recommendations by the first follow-up and of those who complied, 81% reported improvements in their child’s sleep and/or daytime behavior. Of those who did not comply by first follow-up, only 28% saw improvement. Of those who had second follow-up, 89% of caregivers reported improvement in their child’s sleep and/or daytime behavior. Conclusion Time-limited models of community-based sleep educational interventions within a clinical setting are reported by caregivers and clinicians to be an effective method at delivering sleep education to families and improving sleep for children with IDD. Compliance with recommendations was associated with a higher proportion of improvement in sleep and/or daytime behavior. Support (If Any) This work was supported by the Vanderbilt Kennedy Center for Excellence in Developmental Disabilities

0817 Conquering Two Sleep Birds with One Iron stone: The Case of Resolved Restless Sleep Disorder and Parasomnia with Iron Therapy

Abstract Introduction Restless Sleep Disorder (RSD) is characterized by frequent nocturnal movements of large muscle groups or a complaint of restless sleep by observers with associated daytime dysfunction.1 RSD, like other movement disorders of sleep, is associated with low iron stores.2 Children with RSD have increased NREM sleep instability and a propensity for parasomnia.2 No reports to date have demonstrated the use of iron therapy for parasomnia in patients with RSD. Furthermore, studies are limited in very young children with this disorder as they currently fall outside proposed diagnostic criteria.1 Report of Cases: A 2 year-old male presented to the sleep clinic with parental complaints of nightly sleep initiation and maintenance difficulty, mild snoring, restless sleep, episodes of sleepwalking and night terrors multiple times per week. Symptoms worsened over 6 months and were associated with daytime irritability and behavioral problems. Sleep quality measures assessed progress between visits: the PROMIS Sleep Disturbance (PROMIS SD) and Sleep Related Impairment (PROMIS SRI). Serum ferritin was initially 20ug/L. Polysmnogram demonstrated no significant sleep related breathing disorder, a large muscle group movement index of 14, periodic limb movement index of 3. Initial treatment included oral iron therapy, scheduled awakenings, and hypnotic dose melatonin. The sleep psychologist addressed limit setting and negative sleep associations with improved insomnia symptoms but parasomnia and restless sleep continued. The parent noted reduction in both movements and parasomnia frequency after one month of iron therapy. After a 3 month period on treatment, the parent reported complete cessation of the parasomnia, drastic reduction in restlessness, and near resolution of insomnia. Sleep quality measure PROMIS SD improved by 11, demonstrating reduced sleep disturbance. PROMIS SRI did not change. Ferritin level increased to 47ug/L. Conclusion RSD in a very young child with NREM parasomnia responded to oral iron therapy improving overall sleep quality. This case demonstrates the relationship between relative iron deficiency, RSD and associated parasomnia. Support (If Any) 1. DelRosso LM, Ferri R, Allen RP, et al. Consensus diagnostic criteria for a newly defined pediatric sleep disorder: restless sleep disorder(RSD).SleepMed.2020;75:335-340. 2. Leung W, Singh I, McWilliams S, Stockler S, Ipsiroglu OS. Iron deficiency and sleep - A scoping review. SleepMedRev.2020;51:101274

0278 Isolated REM sleep behavior disorder is associated with 24-hour rhythm disruption

Abstract Introduction Isolated REM sleep behavior disorder (iRBD), the loss of motor inhibition during REM sleep, is a symptom of prodromal Lewy body disease, with over 80% of iRBD patients eventually phenoconverting to Parkinson’s disease or Dementia with Lewy bodies. Rest-activity rhythm disruption, also an established predictor of Parkinson’s disease, has not been well characterized in patients with iRBD. Here, we tested the hypothesis that accelerometer-based measures of 24-hour rhythms would indicate greater fragmentation and variability in patients with iRBD relative to matched healthy controls. Methods N=36 patients with iRBD recruited from the Stanford Sleep Clinic had 24-hour activity continuously monitored for (mean ± SD) 25.3 ± 8.4 days using an Axivity wristworn device. A control dataset of age, sex, and body mass index matched healthy older adults (N=126) was selected from the UK Biobank accelerometer dataset. Raw accelerometer data were processed using the GGIR, nparACT, and ActCR software packages in R, with a focus on nonparametric and 5-parameter cosinor measures of 24-hour rhythms. Functional PCA analyses (fPCA) were applied to detect overall differences in 24-hour rhythms and during sleep. Results Patients with iRBD had lower interdaily stability and higher intradaily variability than controls (IS, Cohen’s d=-1.15, Mann-Whitney test p&amp;lt;0.001; IV, d=0.46, p=0.04). Cosine amplitude was lower in iRBD patients (d=-0.22, p=0.001), but mean activity (mesor) did not differ (d=0.03, p=0.31), suggesting differences in rest-activity patterns rather than overall activity levels. A shape naïve approach utilizing fPCA indicated that increased activity during the night may explain overall rhythm differences observed in iRBD. Conclusion Multiple metrics of rest-activity rhythms support the hypothesis that 24-hour rhythms are disrupted in iRBD. It remains to be determined whether rhythm fragmentation in iRBD reflects higher activity levels during REM sleep, or if dysfunctional rhythms represent the direct effects of degenerating sleep-wake regulating circuits, indicating the early stages of Lewy body disease. Support (If Any) NIA F32AG074625 to JW; NIA P30AG066515 to JW, KP, and EM

0364 GOOD Sleep Care: Geospatial Optimization of Distant Sleep Care in the VA

Abstract Introduction Obstructive Sleep Apnea (OSA) is very prevalent in the Veterans Administrations (VA) clinical population, affecting about 24% of Veterans. Sleep medicine services in VA suffers from uneven distribution, which especially affects Veterans in rural populations, where care is often not available except by long distance travel. Travel burden is increasingly recognized as a burden on Veteran care that can be ameliorated by telemedicine. Little is known about travel burden and few attempts have been made to quantify it. We have attempted to quantify travel burden for rural Veterans using data from VA's Office of Rural Health supported Enterprise Wide Initiative for Telesleep Medicine. In this project we focus on travel from a Veteran's home to a facility-based sleep clinic visit (traditional face-face visit) vs. how much travel would be avoided if visits were performed using video-based telemedicine with the Veteran at his/her residence. Methods Purpose built geocoding software (validated in prior studies) was used to quantify the driving distance from the Veterans home zipcode to the zipcode of the facility where the visits would were performed. The data were taken from the VA's national corporate data warehouse (CDW). Over 4 million sleep encounters were coded. CPT4 codes were used to define the clinic visit encounters from 2016 through 2020. We set the travel range where telemedicine is reasonable based on distance at greater than 40 miles from the VA medical center which is how VA currently defines "distant travel". Results No. of Encounters (thous) 2016, 557; 2017, 623; 2018, 678; 2019, 667; 2020, 420Miles ObsTravel (mil) 2016, 38; 2017, 42; 2018, 45; 2019, 43; 2020, 27 Miles Travel if telemed used (mil) 2016, 25; 2017, 27; 2018, 29; 2019, 27: 2020, 17Difference (mil miles) 2016, 13; 2017, 15; 2018, 16; 2019, 16 2020, 10Between 10 and 16 million miles could be saved each year for sleep medicine visits if all travel &amp;gt; 40 miles was converted to video home visits. Conclusion Travel burden in this analysis, defined by miles driven to and from a sleep medicine encounter, could be dramatically reduced if telemedicine visits were used for sleep apnea evaluation and management. This reduction in travel equates to a reduction in automobile related use-costs, lower carbon footprint, fewer automobile crashes with injury and death. Assuming that clinical effectiveness of home telemedicine is comparable to traditional visits, these data support the vigorous adoption of telemedicine for sleep medicine services. Support (If Any) VA Office of Rural Health; Measurement QUERI, San Francisco VA Medical