Citations

Abstract Introduction Obstructive Sleep Apnea (OSA) in children and adolescents is commonly discussed amongst dental specialists. Physical attributes such as a high and narrow palate, dolichofacial appearance, and retrognathic mandible are reported to increase pediatric risk for OSA. Previous research states rapid maxillary expansion decreases AHI in children with OSA and may be an effective treatment option. Current literature does not report a consistent method of measuring a maxillary transverse deficiency nor does it report a numerical maxillary threshold deficiency that requires expansion in pediatric patients with OSA. Our aims are to compare two different orthodontic diagnostic methods for measuring the maxillary transverse dimension and to assess whether patients diagnosed with mild, moderate, or severe OSA have a numerical threshold for maxillary deficiency. Methods Participants were ages 7-17 years old (average 11.7 years) with no history of orthodontic treatment, craniofacial syndromes, craniosynostosis forms, or nasal abnormalities. Those with and without adenoids and tonsils were included. Participants presented to the Mayo Clinic Sleep Center for their polysomnogram. Their dentition was scanned, and a digital model was rendered. The maxillary transverse dimension was measured via two different methods: McNamara’s Analysis and Andrew’s Six Elements of Orofacial Harmony. Results There were 65 participants: 31 diagnosed with OSA (13 Mild, 4 Moderate, 5 Severe, and 9 Other) and 34 without (controls). Patients in the Other category were diagnosed based on clinical findings. No statistical difference was found between the maxillary transverse measurements of patients with versus without OSA or between the OSA categories. Patients with OSA were more likely to have permanent teeth (61.3% vs 32.4%, p=0.019), tonsils removed (54.8% vs 26.5%, p=0.020), and to have snored during the PSG (83.9% vs 55.9%, p=0.048). Conclusion Conclusions based on this pilot study should be interpreted carefully due to limited sample sizes. No statistically significant differences of the maxillary transverse dimension were found between those with and without OSA using either diagnostic method. No numerical maxillary deficiency threshold was found. Maxillary expansion should not be recommended based on OSA diagnosis alone. Referral to a dental specialist is recommended based on dental needs. Support (if any) Support was provided by Mayo Clinic CTSA grant UL1TR002377.

Abstract Introduction The COVID-19 pandemic caused by SARS-CoV-2 continues to result in significant morbidity and mortality on a global scale. Prior studies have examined the effectiveness of non-COVID vaccines in setting of sleep disturbances. This study evaluated data from a large national database to examine the relationship between the risk of breakthrough COVID-19 infections in patients with certain sleep related disturbances. Methods Real-time search and analysis using the TriNetX platform to evaluate risk of COVID-19 breakthrough infections (BTI) for patients having ICD-10 diagnoses relating to insomnia, circadian rhythm disorders, and inadequate sleep. The sleep disorder and control cohorts underwent propensity matching including factors for age, gender, race, ethnicity, and multiple co-morbid conditions. Results Of 24,720 patients identified as having a sleep disturbance relating to insomnia, circadian rhythm disorder, or inadequate sleep, 815 (3.2%) were found to have a developed a BTI. There was a significant increased risk of BTI noted between the sleep disorder and control cohorts (adjusted odds ratio (aOR) of 1.40, 95% confidence interval (CI) of 1.23-1.58). Subgroup analysis showed an elevated risk for BTI receiving two doses (aOR 1.53, 95% CI 1.24 – 1.89) versus three doses (aOR 1.45, 95% CI 1.24 – 1.69). Patients with the sleep disturbance were not found to be at an increased risk of hospitalization, intubation, death, or composite outcome of death and intubation. Conclusion The presence of having a diagnosis of insomnia, circadian rhythm disorder, or inadequate sleep was associated with increased risk of COVID-19 breakthrough infection. Support (if any)

Abstract Introduction Consumption of diet rich in high saturated fats has been associated with a higher degree of daytime sleepiness. A whole-food, plant-based (WFPB) dietary pattern, which is low in saturated fat, has been shown to be beneficial in weight loss and other health conditions. Patients with obstructive sleep apnea (OSA) frequently experience excessive daytime sleepiness despite treatment. This study aims to assess the effect of a short term (21 days) WFPB diet on daytime sleepiness in patients with obstructive sleep apnea. Methods Patients were recruited from the Mayo Clinic Jacksonville sleep clinic who have a diagnosis of OSA who are on PAP therapy but have daytime sleepiness with Epworth Sleepiness Scale (ESS) score of 5 or above. Participants were asked to follow a strict WFPB diet for 21 days using the Fork Over Knives handbook as a guide. They were also asked to complete ESS before switching to and after completing a WFPB diet for 21 days. Results A total of 10 participants completed the 21-day WFPB diet. Eight out of ten participants had reported a reduction in daytime sleepiness. Overall, we found a mean decrease in ESS score of 3.8 in all participants, with 3 patients had a significant decrease in ESS score of ≥ 7. All participants completed the study with ≥ 90% adherence to a WFPB diet. In addition, participants also reported a mean weight loss of 4.2 kg. Two participants noted headaches during this 21-day period. Conclusion Significant improvement with daytime sleepiness was found in patients who switched to a WFPB diet for 21 days. No significant correlation between improvement in ESS and weight loss was found. Support (if any)

Abstract Introduction The prevalence of obstructive sleep apnea (OSA) is high in patients with systolic heart failure (HFrEF) and has been associated with poor prognosis in this patient population. The impact of positive airway pressure (PAP) therapy in patients with OSA and HFrEF remains unclear. This retrospective study sought to investigate the association between 1-year adherence to PAP therapy and healthcare resource utilization (HCRU) in patients with newly diagnosed OSA and comorbid HFrEF. Methods A national sample of administrative claims data linked to objective PAP therapy usage was used for this analysis. Included patients either had two healthcare encounters or one hospitalization with a systolic heart failure ICD-10 diagnosis code the year prior to being diagnosed with OSA and initiated on PAP therapy. HCRU was measured as a composite outcome of hospitalizations, and emergency room (ER) visits. Propensity score matching was used to create well-balanced groups with differing PAP adherence levels to assess the association with 1-year HCRU outcomes. Risk-adjusted models were used to generate the number needed to treat (NNT) that referred to the number of patients that need to become adherent to PAP from non-adherent to avoid 1 visit. Results We identified 3,182 patients with OSA and comorbid HFrEF, and after propensity score matching, 738 patients remained in each group (adherent vs. non-adherent). After 1 year of PAP therapy, adherent patients had fewer visits than non-adherent patients (0.92 vs. 1.15 visits per subject, p = 0.006), which was driven by a 24% reduction in ER visits for adherent patients. Composite hospitalization and ER visit costs were lower in adherent versus non-adherent patients ($3,500 vs. $5,879, p=0.03). The NNT for the entire cohort to avoid one visit was 1.5 patients. Conclusion HFrEF patients with comorbid OSA who were adherent to PAP therapy for 1 year have fewer composite hospitalizations and ER visits than patients that were not adherent. These results highlight the clinical and economic benefits of treating OSA in HFrEF patients. Support (if any) Funding Source: ResMed

Abstract Introduction Introduction: Rapid eye movement (REM) sleep behavior disorder (RBD) is strongly associated with progressive phenoconversion to an overt synucleinopathy (e.g., parkinsonism). Neurotrauma [i.e., traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD)], increases the odds of RBD diagnosis by ~2.5-fold and is associated with an increased later diagnosis of Parkinson’s Disease (PD), a service-connected illness in Veterans. Thus, RBD and neurotrauma are both independently associated with parkinsonism; however, it is unclear how neurotrauma influences neurological symptoms and exam findings in patients with RBD. Methods Methods: Participants ≥18 years of age with overnight polysomnogram-confirmed RBD were enrolled between 8/2018 to 4/2021 as part of the North American Prodromal Synucleinopathy (NAPS) Consortium. Standardized assessments for RBD, TBI, and PTSD history, as well as cognitive, motor, sensory and autonomic function were completed. This sub-study applied a cross-sectional, case-control (1:4 ratio) analysis comparing cases (n=24; RBD+TBI+PTSD) to controls (n=96; RBD) matched for age (±2 years), sex, and years of education (±2 years). Results Results: Participants with neurotrauma reported an earlier age of RBD symptom onset and more severe RBD phenotype, more severe anxiety and depression, greater frequency of hypertension, and significantly worse cognitive, motor, and autonomic function compared to participants without neurotrauma. Conclusion Conclusion: This cross-sectional, matched case:control study showed that individuals with comorbid neurotrauma and RBD have significantly worse neurological outcomes related to common features of early parkinsonism. Although confirmatory longitudinal studies are still ongoing, these results may be a sign of further/faster progression of synucleinopathy in those with comorbid neurotrauma and RBD. Support (if any) Support: NIH R34 AG056639, NIH U19 AG071754, VA RRD 1K2 RX002947, Parkinsons Center of Oregon

Abstract Introduction Most older adults with isolated REM sleep behavior disorder (iRBD) are men, yet in younger adults there is greater parity between the sexes. Whether the clinical characteristics between women and men with iRBD may differ remains unclear. We aimed to analyze presenting clinical and demographic characteristics of iRBD in men and women. Methods We identified 130 women and 130 men with PSG confirmed iRBD who were matched for time of polysomnographic diagnosis, abstracted their clinical histories, and comparatively analyzed clinical characteristics between the sexes. Results RBD symptom onset average age (50.4 ± 20.0 vs. 55.4 ±16.9 years, p=0.03) and age at diagnosis (56.4 ±16.7 vs. 62.5 ± 13.3 years, p< 0.01) were younger in women than in men. Injury frequency was similar between groups. Antidepressant use prior to diagnosis (80.8% vs 53.0%, p< 0.01), psychiatric comorbidity (79.8% vs. 50.8%, p< 0.01) and chronic pain syndrome (39.2% vs. 17.4%, p< 0.01) diagnoses were more frequent in women than men. Insomnia (31.5% vs. 18.2%, p= 0.01), hypersomnoence (50.8% vs 37.9%, p=0.04) and overlap parasomnia disorder (13.8% vs 9.8%, p=0.06) were more frequent in women than men, while sleep apnea (43.1% vs. 70.5%, p < 0.01.) and vascular co-morbidity (62.3% vs 83.3%, p< 0.01) occurred more frequently in men than women. Autoimmunity was similar between sexes. Conclusion Women were younger when diagnosed, and had more frequent psychiatric diagnoses and antidepressant use, with different comorbid sleep disturbances and comorbidities than men with iRBD. Key sex differences in iRBD could imply different etiologies and aid accurate and timely diagnosis. Support (if any)

Abstract Introduction In a recent study, most patients diagnosed with isolated REM sleep behavior disorder (iRBD) preferred their physician discussed their risk for developing a future neurodegenerative disorder (NDD) such as parkinsonism or dementia (PD). In the Mayo Clinic email survey, 75% would lose trust in their physician if PD-risk was not discussed following an iRBD diagnosis. For this survey, questions were designed to investigate preferences for how sleep physicians might communicate to community-based adults about risk of a NDD. Methods A survey was administered to Rotary Club attendees prior to a sleep and neurodegenerative disease presentation, with options for responses being either strongly disagree, disagree, neutral, agree, or strongly agree. Thirty-four surveys were obtained from approximately equal numbers of men and women with estimated ages above 50 years. Personal information were not obtained (i.e., sex and age). Results The vast majority of respondents wanted their physician to ask their preference prior to sharing NDD risk (86% strongly agreed or agreed), while virtually all would lose trust in their physician if he/she did not discuss their NDD risk (97% strongly agreed/agreed). If identified with NDD risk, responders would seek out information about medications and adaptive therapies that could delay onset (97% strongly agreed/agreed), while only about half currently had a good understanding of lifestyle patterns that might help delay onset (47% strongly agreed/agreed and 47% disagreed/strongly disagreed). Not knowing when memory problems might begin would cause most responders to feel anxious (85% strongly agreed/agreed). Conclusion Those surveyed wanted their physician to ask their preference prior to sharing NDD risk, but virtually all would lose trust in their health care provider if the information was known but not shared. There appears to be a role for physicians in educating those who may be at NDD risk about interventions that could delay onset of NDD, given approximately half have a limited understanding of lifestyle patterns that could help delay onset. Further, routine follow-up for changes in prodromal NDD biomarker severity might help to reduce anxiety in the 85% of those concerned about when memory problems might begin. Support (if any) NIA-R44AG050326

Abstract Introduction Restless legs syndrome (RLS) can dramatically impair sleep quality and quality of life. Some patients have insufficient treatment response or intolerance to available pharmacological options. Exploration of novel therapeutic approaches is needed. Methods We report a case of spinal cord stimulation (SCS) providing benefit in RLS. We also performed a scoping review of SCS in RLS with comprehensive literature search of MEDLINE, EMBASE, Cochrane, and Scopus. Results A 77-year-old woman with DM2, OSA (on ASV), depression, familial RLS and iron deficiency with typical RLS symptoms for all of her adult life presented for management in 2000. In 2011 she developed intractable painful peripheral neuropathy and chronic back pain. Levodopa, pramipexole, oral/intravenous iron, gabapentin, pregabalin, tramadol, oxycodone, and methadone were ineffective or poorly tolerated. A 7-day percutaneous SCS trial resulted in RLS symptoms improvement initially by 50%. A Medtronic stimulator with lead placement at T8-T9 was implanted. 6 months later, the patient toggled between a tonic program (2.1-4.6 mA, 200 us, 50 Hz) and a sub-perception, differential target multiplexed program duty-cycled to 1:2 on:off (3.7 mA, 170 us, 300 Hz). She reported 75% improvement in RLS symptoms. Pain improved by 50%. Total daily dose of Oral Morphine Equivalents was reduced from 48.75mg/day to 37.5mg/day, with a stable once daily dose of 400 mg gabapentin at night. Uninterrupted sleep went from 2-5 hours to 6 hours. RLS worsened when the device was off. Our case corroborates the current evidence of benefit of SCS for RLS from the literature. We identified other 16 unique patients from case reports and series who had undergone SCS for RLS. Leads were most often implanted in mid or low thoracic levels. Stimulation waveforms were high frequency in 4 patients, tonic in 3 patients, burst stimulation in 1 patient, and undescribed in the others. All patients had RLS symptom reduction. Comorbid pain was reported in 14 patients, which also improved with SCS. Complication with lead erosion was reported in one case. Conclusion SCS remains a promising therapeutic approach for refractory RLS that deserves further investigation. SCS may reduce hyperexcitability seen in RLS by modulating dysfunctional spinal, subcortical, and cortical networks. Support (if any)

Abstract Introduction Sodium oxybate (SXB) is strongly recommended for treatment of narcolepsy. Patients treated with available immediate-release oxybates are required to awaken for a second dose 2.5–4 hours after the bedtime dose to cover a full night of sleep. This study characterized SXB treatment patterns and discontinuation in narcolepsy patients. Methods Mayo Clinic patients from 1975–2020 were identified using an electronic health record–based search. Patients with ≥1 narcolepsy-specific ICD-9/-10 code and ≥1 diagnostic mention of narcolepsy in clinical notes (identified using a natural-language-processing [NLP] algorithm) were included. NLP was used to identify SXB non-use events with manual chart reviews performed to characterize reasons for discontinuation, switching, or missing the second dose and effects of missing the second dose. Results Of the patients with narcolepsy prescribed SXB (n=351; mean age at first diagnosis code observed at Mayo Clinic, 32 y [IQR: 23.2–46.1]; 65.5% female; 92.3% white), 113 (32.2%) had clinical notes indicating discontinuation of SXB, with 71 (20.2%) including reasons for discontinuation. The most common reasons for discontinuation (n≥5) included lack of efficacy (n=11), side effects (n=10), gastrointestinal side effects (n=10), neurological side effects (n=9), psychiatric side effects (n=8), lack of access (insurance/cost, n=10), and resolution/absence of cataplexy (n=5). Mentions of switching from SXB to other drugs (n=12 patients) included switching to stimulants (mixed amphetamine salts, n=3; dextroamphetamine, n=2; methylphenidate, n=1), sedative hypnotics (zolpidem, n=2), antidepressants (mirtazapine, n=1), and wake-promoting agents (solriamfetol, n=1). Of the 38 patients (10.8%) with mentions of missing the second nightly SXB dose, reasons were recorded for 24 (63.2%), including inability to wake up (n=14), forgetting the second dose (n=3), and having to wake up early the following day (n=3). Consequences of missing the second dose were recorded for a small subset (increased cataplexy, n=4; lower daytime alertness, n=3; awakens earlier, n=1; tiredness, n=1). Conclusion Limited data are available regarding real-world use of SXB. This novel study used a combination of NLP algorithm and manual chart review to identify difficulties patients have with the second, middle-of-the night immediate-release oxybate dose and patient-experienced consequences of not adhering to the prescribed dosing regimen. Support (if any) Avadel Pharmaceuticals

Abstract Introduction Narcolepsy is a rare, chronic sleep disorder whose symptoms detrimentally impact quality of life. Narcolepsy has a complex phenotype associated with multiple comorbid conditions. This is the first study to use aggregate electronic health record (EHR) data to characterize the demographics and comorbidities of patients with narcolepsy. Methods An EHR-based search identified first-time Mayo Clinic patients between 2000–2020. Included patients had ≥1 narcolepsy-specific ICD-9/10 code and ≥1 disease-supportive statement in the clinical notes (identified using a natural language processing algorithm). A control cohort was propensity-matched for birth year, age at first institutional encounter, sex, race, ethnicity, number of diagnosis codes, and mortality. Common comorbidities were compared and ranked between cohorts by odds ratio (OR); P values were adjusted and calculated based on Bonferroni correction. Results In the EHR database (N=6,389,186 patients), 2057 patients with narcolepsy were identified (median age at first presentation to Mayo clinic, 32 y [range, 17–48]; 59.6% female; 92.6% white; 89.2% non-Hispanic) and propensity-matched with a control cohort of 2057 patients (median age at first presentation to Mayo clinic, 35 y [range, 12–52]; 58.9% female; 94.6% white; 84.5% non-Hispanic). Among the top comorbidities that occurred more frequently in the narcolepsy cohort compared to the control cohort (OR [95% CI]; P< 0.001]) were sleep disorders (restless leg syndrome, 3.94 [3.09–5.02]; obstructive sleep apnea, 3.27 [2.83–3.79]; insomnia, 1.84 [1.57–2.17]); mood disorders (depression, 2.11 [1.86-2.40]; dysthymia, 1.86 [1.54–2.25]; anxiety, 1.67 [1.46–1.89]); and pain disorders (chronic pain syndrome, 2.20 [1.76–2.76]; migraine, 1.96 [1.66–2.31]; fibromyalgia, 1.90 [1.61–2.25]; carpal tunnel syndrome, 1.80 [1.46–2.22]; myalgia, 1.69 [1.45–1.97]). Other comorbidities statistically significantly associated with narcolepsy were (OR range, 1.33–1.95) irritable bowel syndrome (P< 0.001), asthma (P< 0.001), cervical spondylosis (P< 0.01), syncope (P< 0.01), and hypothyroidism (P< 0.05). Conclusion This propensity-matched cohort study affirmed prior studies of increased psychiatric and sleep disorders in patients with narcolepsy. Narcolepsy patients were twice as likely to experience chronic pain syndrome compared to the matched control group. Understanding common narcolepsy comorbidities may help optimize treatment efficacy and increase understanding of the medical/psychiatric challenges of narcolepsy patients. Support (if any) Avadel Pharmaceuticals