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Alyssa Cairns,1 Richard Bogan1–41Sleepmed, Inc., Columbia, SC, USA; 2Bogan Sleep Consultants, LLC, Columbia, SC, USA; 3The University of South Carolina Medical School, Columbia, SC, USA; 4The Medical University of South Carolina, Charleston, SC, USACorrespondence: Alyssa CairnsSleepMed, Inc., 700 Gervais Street, Suite 200, Columbia, SC 29201, USATel +1 803 779 5454Email acairns@sleepmedinc.comIntroduction: Nasal congestion is common, burdensome, and costly. Current treatments are limited by partial/temporary relief and untoward side-effects. The goal of this study was to evaluate the performance of a novel, non-pharmacologic nasal device designed to reduce nasal congestion via simultaneous administration of acoustic vibration and gentle oscillating expiratory pressure.Materials and methods: Patients were recruited from a tertiary care sleep clinic and all reported moderate-to-severe nasal congestion for >2 weeks (N=14; 64% female; 71% Caucasian). Visual analog scale (VAS) (10 items) quantifying nasal congestion and ease-of-breathing were administered before and after SinuSonic application for 2–5 mins. Global and clinical impressions of change were assessed post-administration.Results: Wilcoxon signed-rank tests indicated that post-test ranks were statistically improved from pre-test ranks for both VAS measures (congestion p=0.002; ease-of-breathing p=0.003). A binomial test indicated that the proportion of patients with ≥ minimal improvement on clinical and global impressions of change was higher than expected (100% vs expected 75%, p=0.018).Conclusion: Overall, outcomes were encouraging from this small pilot study with effect sizes in the moderate to large range and no reports of discomfort. It is probable that this device will provide acute, and possibly chronic, relief of nasal congestion with minimal side-effects.Keywords: humming, sinus, congestion

Alyssa Cairns,1 Greg Poulos,1 Richard Bogan,1-3 1Research Division, SleepMed, Inc., 2School of Medicine, The University of South Carolina Medical School, Columbia, 3School of Medicine, The Medical University of South Carolina, Charleston, SC, USA Study objectives: To evaluate sex differences in predictors of obstructive sleep apnea (OSA) as per outcomes from home sleep apnea testing. Design: This was a retrospective analysis of a large repository of anonymous test results and pretest risk factors for OSA. Setting and patients: A total of 272,705 patients were referred for home sleep apnea testing from a variety of clinical practices for suspected sleep disordered breathing across North America from 2009 to 2013. Interventions: Not applicable. Measurements and results: Predictors of OSA (apnea hypopnea index4%≥5) were evaluated by multiple logistic regression; sex differences were evaluated by interaction effects. Middle age was the single most robust predictor of OSA for both sexes and was particularly foretelling for females (P

Logan D Schneider,1 Anne Marie Morse,2 Michael J Strunc,3 Joyce K Lee-Iannotti,4 Richard K Bogan5 1Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA; 2Janet Weis Children’s Hospital, Geisinger Medical Center, Danville, PA, USA; 3The Center for Pediatric Sleep Medicine, Children’s Hospital of The King’s Daughters, Norfolk, VA, USA; 4Department of Neurology, The University of Arizona College of Medicine, Phoenix, AZ, USA; 5Department of Pulmonology, University of South Carolina School of Medicine, Columbia, SC, USACorrespondence: Logan D Schneider, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 450 Broadway St, Pavilion C 2nd Fl MC 5704, Redwood City, CA, 94063, USA, Tel +1 650 723-6601, Fax +1 650 721-3448, Email logands@gmail.comAbstract: Narcolepsy and idiopathic hypersomnia are chronic conditions that negatively affect alertness, mental and physical energy, functioning, and quality of life (QoL). Calcium, magnesium, potassium, and sodium oxybates (low-sodium oxybate; LXB) is an oxybate formulation with 92% less sodium than sodium oxybate (SXB; a treatment for narcolepsy) and the same active moiety. LXB is approved in the US for treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age or older with narcolepsy, and idiopathic hypersomnia in adults. In Phase 3 clinical trials, LXB exhibited a safety profile consistent with that of SXB in narcolepsy. Besides continued efficacy in treating symptoms, potential benefits of long-term LXB treatment include flexible optimization of dosing and regimen, improvement of QoL and functioning, weight loss, and (relative to SXB in narcolepsy) health benefits of reduced sodium content. Dosing of LXB is twice nightly (for narcolepsy) or once or twice nightly (for idiopathic hypersomnia) based on patient characteristics and response, and individualized titration can be leveraged over the long term as a patient’s life circumstances change. Patients with narcolepsy transitioning from SXB initiate LXB at the same dose, and most patients require no further changes to achieve similar efficacy and tolerability. Improvements in functioning and QoL with LXB treatment could have cascading positive effects in multiple domains, particularly in younger patients. In clinical trials, LXB was associated with weight loss in both narcolepsy (in which obesity is a well-established comorbidity) and idiopathic hypersomnia, only occasionally leading participants to be underweight. As both narcolepsy and idiopathic hypersomnia are associated with increased risk of cardiometabolic and cardiovascular comorbidities, limiting medication-related sodium intake with LXB may have significant health benefits, although this has not yet been verified prospectively due to the prolonged follow-up required. LXB is a promising long-term treatment for narcolepsy and idiopathic hypersomnia.Plain Language Summary: Narcolepsy and idiopathic hypersomnia are disorders that make people feel very sleepy. Low-sodium oxybate (LXB) is a medicine for these disorders. Doctors think LXB works on parts of the brain that keep people awake. LXB may quiet those brain parts down at night by reducing their electrical activity, which helps people sleep better. LXB wears off by the morning, so people can wake up normally and feel more alert the next day. LXB has less sodium (which is part of salt) than a medicine called sodium oxybate. Sodium oxybate has been used for narcolepsy for more than 20 years. LXB has several benefits. First, LXB may be healthier than medicines that contain a lot of sodium, such as a high-sodium oxybate. This is because sodium can increase blood pressure and risk of heart disease. Second, LXB can be taken twice each night for narcolepsy, or once or twice each night for idiopathic hypersomnia. This depends on a person’s lifestyle, how well the medicine is working, and side effects. Third, people taking LXB are more able to work and do other activities and have better quality of life. Finally, people taking LXB may lose weight. This can help overweight or obese people.Keywords: cardiovascular, dosing, LXB, hypersomnolence, quality of life, weight loss

Michael J Thorpy,1 Isabelle Arnulf,2 Nancy Foldvary-Schaefer,3 Anne Marie Morse,4 Karel Šonka,5 Patricia Chandler,6 Luke Hickey,7 Abby Chen,6 Jed Black,6,8 Amanda Sterkel,6 Dan Chen,9 Richard K Bogan,10 Yves Dauvilliers11,12 1Albert Einstein College of Medicine, Bronx, NY, USA; 2Sleep Disorder Unit, Pitié-Salpêtrière Hospital and Sorbonne University, Paris, France; 3Cleveland Clinic Sleep Disorders Center, Department of Neurology, Lerner College of Medicine, Cleveland, OH, USA; 4Janet Weis Children’s Hospital, Geisinger, Danville, PA, USA; 5Department of Neurology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic; 6Jazz Pharmaceuticals, Palo Alto, CA, USA; 7Jazz Pharmaceuticals, Philadelphia, PA, USA; 8Stanford University Center for Sleep Sciences and Medicine, Palo Alto, CA, USA; 9Formerly Jazz Pharmaceuticals, Palo Alto, CA, USA; 10University of South Carolina School of Medicine, Columbia, SC, USA; 11Sleep and Wake Disorders Centre, Department of Neurology, Gui de Chauliac Hospital, Montpellier, France; 12University of Montpellier, INSERM Institute Neuroscience Montpellier (INM), Montpellier, FranceCorrespondence: Michael J Thorpy, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461, USA, Tel +1 718 920-4841, Fax +1 718 798-4352, Email michael.thorpy@einsteinmed.orgPurpose: To report the efficacy and safety of lower-sodium oxybate (LXB; Xywav®) during the open-label titration and optimization period (OLT) and stable-dose period (SDP) in a clinical study for the treatment of idiopathic hypersomnia.Patients and Methods: Data were collected during treatment titration and optimization in a phase 3 randomized withdrawal trial in adults (18– 75 years of age) with idiopathic hypersomnia who took LXB treatment (once, twice, or thrice nightly, administered orally) in the OLT (10– 14 weeks), followed by the 2-week, open-label SDP. Endpoints included the Epworth Sleepiness Scale (ESS), Idiopathic Hypersomnia Severity Scale (IHSS), Patient Global Impression of Change, Clinical Global Impression of Change, Functional Outcomes of Sleep Questionnaire (FOSQ)-10, and Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP).Results: The safety population included 154 participants; the modified intent-to-treat population comprised 115 participants. During open-label treatment, mean (SD) ESS scores improved (decreased) from 15.7 (3.8) at baseline to 6.1 (4.0) at end of SDP, and IHSS scores improved (decreased) from 31.6 (8.3) to 15.3 (8.5). Improvements were also observed during OLT in each individual IHSS item and in FOSQ-10 and WPAI:SHP scores. Thirty-five (22.7%) participants discontinued during OLT and SDP, 22 (14.3%) due to treatment-emergent adverse events (TEAEs) during OLT and SDP. The most frequent TEAEs in the first 4 weeks were nausea, headache, dizziness, and dry mouth; TEAE incidence decreased throughout OLT and SDP (weeks 1– 4, n = 87 [56.5%]; weeks 13– 16, n = 39 [31.7%]).Conclusion: During open-label treatment with LXB, participants showed clinically meaningful improvements in idiopathic hypersomnia symptoms and in quality of life and functional measures. TEAE incidence declined over LXB titration and optimization.Keywords: excessive daytime sleepiness, hypersomnolence, quality of life, pharmacotherapy

Yves Dauvilliers,1,2 Richard K Bogan,3 Karel Šonka,4 Markku Partinen,5 Nancy Foldvary-Schaefer,6 Michael J Thorpy7 1Sleep and Wake Disorders Centre, Department of Neurology, Gui de Chauliac Hospital, Montpellier, France; 2University of Montpellier, INSERM Institute Neuroscience Montpellier (INM), Montpellier, France; 3University of South Carolina School of Medicine, Columbia, SC, USA; 4Department of Neurology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic; 5Helsinki Sleep Clinic, Terveystalo Healthcare, and Department of Clinical Neurosciences, University of Helsinki, Helsinki, Finland; 6Sleep Disorders Center, Department of Neurology, Cleveland Clinic, Cleveland, OH, USA; 7Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USACorrespondence: Yves Dauvilliers, 80 Avenue Augustin Fliche, Montpellier, 34295, France, Tel +334 67 33 72 77, Email ydauvilliers@yahoo.frAbstract: Lower-sodium oxybate (LXB) is an oxybate medication approved to treat cataplexy or excessive daytime sleepiness (EDS) in patients with narcolepsy 7 years of age and older in the United States. LXB was developed as an alternative to sodium oxybate (SXB), because the incidence of cardiovascular comorbidities is higher in patients with narcolepsy and there is an elevated cardiovascular risk associated with high sodium consumption. LXB has a unique formulation of calcium, magnesium, potassium, and sodium ions, containing 92% less sodium than SXB. Whereas the active oxybate moiety is the same for LXB and SXB, their pharmacokinetic profiles are not bioequivalent; therefore, a phase 3 trial in participants with narcolepsy was conducted for LXB. This review summarizes the background on oxybate as a therapeutic agent and its potential mechanism of action on the gamma-aminobutyric acid type B (GABAB) receptor at noradrenergic and dopaminergic neurons, as well as at thalamocortical neurons. The rationale leading to the development of LXB as a lower-sodium alternative to SXB and the key efficacy and safety data supporting its approval for both adult and pediatric patients with narcolepsy are also discussed. LXB was approved in August 2021 in the United States for the treatment of idiopathic hypersomnia in adults. Potential future developments in the field of oxybate medications may include novel formulations and expanded indications for other diseases.Graphical Abstract: Keywords: narcolepsy, therapeutics, drug development, cataplexy, excessive daytime sleepiness, idiopathic hypersomnia

Wesley Elon Fleming,1 Jon-Erik C Holty,2 Richard K Bogan,3 Dennis Hwang,4 Aliya S Ferouz-Colborn,4 Rohit Budhiraja,5 Susan Redline,5 Edith Mensah-Osman,6 Nadir Ishag Osman,6 Qing Li,7 Armaghan Azad,1 Susann Podolak,1 Michael K Samoszuk,8 Amabelle B Cruz,8 Yang Bai,8 Jiuliu Lu,8 John S Riley,8 Paula C Southwick8 1Sleep Center Orange County, Irvine, CA, USA; 2Stanford Medical School, VA Palo Alto Health Care System, Pulmonary, Critical Care and Sleep Medicine Section, Palo Alto, CA, USA; 3SleepMed Inc., Bogan Sleep Consultants, LLC, Columbia, SC, USA; 4Sleep Medicine Department, Southern California Permanente Medical Group, Kaiser Permanente, Fontana Medical Center, Fontana, CA, USA; 5Division of Sleep Medicine, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA; 6EENA Comprehensive Neurology and Sleep Center, Boynton Beach, FL, USA; 7South Bend Medical Foundation, New Technology and Test Development, South Bend, IN, USA; 8Clinical Research Department, Beckman Coulter, Inc., Brea, CA, USAPurpose: Obstructive sleep apnea (OSA) is a highly prevalent disorder associated with increased risk for cardiovascular disease, diabetes, and other chronic conditions. Unfortunately, up to 90% of individuals with OSA remain without a diagnosis or therapy. We assess the relationship between OSA and blood biomarkers, and test the hypothesis that combinations of markers provide a characteristic OSA signature with diagnostic screening value. This validation study was conducted in an independent cohort in order to replicate findings from a prior feasibility study.Patients and methods: This multicenter prospective study consecutively enrolled adult male subjects with clinically suspected OSA. All subjects underwent overnight sleep studies. An asymptomatic control group was also obtained. Five biomarkers were tested: glycated hemoglobin (HbA1c), C-reactive protein (CRP), uric acid, erythropoietin (EPO), and interleukin-6 (IL-6).Results: The study enrolled 264 subjects. The combination of HbA1c+CRP+EPO (area under the curve 0.78) was superior to the Epworth Sleepiness Scale (ESS; 0.53) and STOP-Bang (0.70) questionnaires. In non-obese subjects, the combination of biomarkers (0.75) was superior to body mass index (BMI; 0.61). Sensitivity and specificity results, respectively, were: HbA1c+CRP+EPO (81% and 60%), ESS (78% and 19%), STOP-Bang (75% and 52%), BMI (81% and 56%), and BMI in non-obese patients (81% and 38%).Conclusion: We verify our hypothesis and replicate our prior feasibility findings that OSA is associated with a characteristic signature cluster of biomarker changes in men. Concurrent elevations of HbA1c, CRP, and EPO levels should generate a high suspicion of OSA and may have utility as an OSA screening tool. Biomarker combinations correlate with OSA severity and, therefore, may assist sleep centers in identifying and triaging higher risk patients for sleep study diagnosis and treatment.Keywords: obstructive sleep apnea, OSA, screening, diagnosis, biomarkers, CRP, HbA1c, erythropoietin, EPO, uric acid, IL-6