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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

What Is This Summary About?: This is a plain language summary of a published article in the journal Sleep . Narcolepsy is a sleep condition that has 2 different subtypes: narcolepsy type 1 and narcolepsy type 2. These are called NT1 and NT2 for short. Sodium oxybate (SXB) is approved to treat excessive daytime sleepiness (EDS) and cataplexy. People with NT1 and NT2 both have EDS, but cataplexy is only present in people with NT1. Limited information is available about how SXB works in people with NT2. This is because previous trials have included only people with NT1 or people with unspecified narcolepsy. For more than 20 years, the only available formulation of this medicine had to be given twice during the night. Many people with narcolepsy find that chronically waking up in the middle of the night for a second dose of SXB is disruptive to themselves or others in their household. People have also reported sleeping through alarm clocks, missing their second dose, and feeling worse the next day. Some people have accidentally taken the second dose too early, putting them at risk for serious adverse effects. These adverse effects may include slow breathing, low blood pressure, or sedation. The US Food and Drug Administration (FDA) approved a medicine called LUMRYZ ™ (sodium oxybate) for extended-release oral suspension in May 2023. LUMRYZ is a once-nightly formulation of SXB (ON-SXB for short) and is taken as a single dose before bedtime. This medicine treats EDS and muscle weakness (also known as cataplexy) in people with narcolepsy. A clinical trial called REST-ON studied ON-SXB to find out if it was better at treating narcolepsy symptoms than a medicine with no active ingredients (placebo). This summary describes a study that tested whether ON-SXB was better than placebo at treating narcolepsy symptoms in people with NT1 or NT2., What Were the Results?: This study showed that compared to people who took placebo, people who took ON-SXB were able to stay awake longer during the day, felt less sleepy during the daytime, had less cataplexy, and had more improvements in their symptoms overall than people who took placebo., What Do the Results Mean?: ON-SXB has been proven effective for people with NT1 or NT2. Unlike prior formulations of SXB, ON-SXB is taken once at bedtime, without requiring waking up in the middle of the night for a second dose.

This perspective on alternatives to positive airway pressure (PAP) therapy for the treatment of obstructive sleep apnea (OSA) summarizes the proceedings of a focus group that was conducted by the Sleep Research Society Foundation. This perspective is from a multidisciplinary panel of experts from sleep medicine, dental sleep medicine, and otolaryngology that aims to identify the current role of oral appliance therapy and hypoglossal nerve stimulation for the treatment of OSA with emphasis on the US practice arena. A secondary aim is to identify-from an implementation science standpoint-the various barriers and facilitators for adoption of non-PAP treatment that includes access to care, multidisciplinary expertise, reimbursement, regulatory aspects, current treatment guidelines, health policies, and other factors related to the delivery of care. The panel has contextualized the review with recent events-such as a large-scale PAP device recall compounded by supply chain woes of the pandemic-and emerging science in the field of OSA and offers solutions for multidisciplinary approaches while identifying knowledge gaps and future research opportunities., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society.)

Background: In the REST-ON clinical trial (NCT02720744), mean sleep latency on the Maintenance of Wakefulness Test (MWT) was significantly improved with extended-release once-nightly sodium oxybate (ON-SXB) vs placebo ( P  < 0.001) in participants with narcolepsy. This post hoc analysis assessed response to treatment and improvement in excessive daytime sleepiness., Methods: Participants with narcolepsy aged ≥16 years were randomized 1:1 to receive ON-SXB (4.5 g, week 1; 6 g, weeks 2-3; 7.5 g, weeks 3-8; and 9 g, weeks 9-13) or placebo. Mean sleep latency on the MWT was measured across 5 trials of ≤30 min each. Post hoc assessments included percentage of participants whose sleep latency improved ≥5, ≥10, ≥15, and ≥20 min and with a mean sleep latency of 30 min., Results: Significantly more participants receiving ON-SXB vs placebo experienced increased mean sleep latency ≥5 min (all doses P  < 0.001), ≥10 min (all doses P  < 0.001), ≥15 min (6 and 7.5 g, P  < 0.001; 9 g, P  < 0.01), and ≥20 min (6 g, P  < 0.01; 7.5 g, P  < 0.001; 9 g, P  < 0.05). More participants receiving ON-SXB had mean sleep latency of 30 min vs placebo (6 g, 5.7 % vs 0 %, respectively [ P  < 0.05]; 7.5 g, 10.5 % vs 1.3 % [ P  < 0.05]; 9 g, 13.2 % vs 5.1 % [ P  = 0.143])., Conclusions: Significantly more participants who received ON-SXB experienced increased mean sleep latency ≥5 to ≥20 min; at the 2 highest doses, >10 % remained awake for the entirety of the MWT. ON-SXB offers a once-at-bedtime treatment option for adults with narcolepsy., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Michael J. Thorpy reports a relationship with Axsome Therapeutics that includes: consulting or advisory. Michael J. Thorpy reports a relationship with Balance Therapeutics that includes: consulting or advisory. Michael J. Thorpy reports a relationship with Eisai that includes: consulting or advisory. Michael J. Thorpy reports a relationship with Avadel Pharmaceuticals that includes: consulting or advisory. Michael J. Thorpy reports a relationship with Harmony BioSciences that includes: consulting or advisory. Michael J. Thorpy reports a relationship with 10.13039/100011096Jazz Pharmaceuticals that includes: consulting or advisory. Michael J. Thorpy reports a relationship with NLS Pharmaceuticals that includes: consulting or advisory. Michael J. Thorpy reports a relationship with Suven Life Sciences Ltd. that includes: consulting or advisory. Michael J. Thorpy reports a relationship with 10.13039/100008373Takeda Pharmaceutical Co that includes: consulting or advisory. Clete A. Kushida reports a relationship with Avadel Pharmaceutical that includes: consulting. Clete A. Kushida reports a relationship with XW Pharma that includes: consulting. Richard Bogan reports a relationship with WaterMark Medical and Health Humming LLC that includes: equity or stocks. Richard Bogan reports a relationship with WaterMark Medical that includes: board membership. Richard Bogan reports a relationship with 10.13039/100011096Jazz Pharmaceuticals that includes: consulting or advisory, funding grants, and speaking and lecture fees. Richard Bogan reports a relationship with Harmony BioSciences that includes: consulting or advisory and speaking and lecture fees. Richard Bogan reports a relationship with 10.13039/100008373Takeda Pharmaceutical Co. that includes: consulting or advisory and funding grants. Richard Bogan reports a relationship with Avadel Pharmaceuticals that includes: consulting or advisory and funding grants. Richard Bogan reports a relationship with Oventus that includes: consulting or advisory. Richard Bogan reports a relationship with BresoTec that includes: funding grants. Richard Bogan reports a relationship with 10.13039/100004326Bayer that includes: funding grants. Richard Bogan reports a relationship with 10.13039/501100016198Idorsia that includes: funding grants. Richard Bogan reports a relationship with Suven Life Sciences Ltd. that includes: funding grants. Richard Bogan reports a relationship with Balance Therapeutics that includes: funding grants. Richard Bogan reports a relationship with 10.13039/100010902Vanda that includes: funding grants. Richard Bogan reports a relationship with 10.13039/100004334Merck that includes: funding grants. Richard Bogan reports a relationship with 10.13039/501100003769Eisai that includes: funding grants and speaking and lecture fees. Richard Bogan reports a relationship with Fresca that includes: funding grants. Richard Bogan reports a relationship with 10.13039/100013410LivaNova that includes: funding grants. Richard Bogan reports a relationship with 10.13039/100004337Roche that includes: funding grants. Richard Bogan reports a relationship with Sommetrics that includes: funding grants. John Winkelman reports a relationship with Avadel Pharmaceuticals that includes: consulting or advisory. John Winkelman reports a relationship with Emalex Biosciences that includes: consulting or advisory. John Winkelman reports a relationship with Noctrix Health that includes: consulting or advisory. John Winkelman reports a relationship with Disc Medicine that includes: consulting or advisory. John Winkelman reports a relationship with 10.13039/501100016198Idorsia Pharmaceuticals that includes: consulting or advisory. John Winkelman reports a relationship with 10.13039/100004334Merck & Co. that includes: funding grants. John Winkelman reports a relationship with 10.13039/100016473American Regent that includes: funding grants. John Winkelman reports a relationship with 10.13039/100000026NIDA that includes: funding grants. John Winkelman reports a relationship with 10.13039/100004087RLS Foundation that includes: funding grants. John Winkelman reports a relationship with Baszucki Brain Research Fund that includes: funding grants. Maurice M. Ohayon reports a relationship with Avadel Pharmaceuticals that includes: consulting or advisory. Maurice M. Ohayon reports a relationship with 10.13039/100008373Takeda Pharmaceutical Co. that includes: consulting or advisory. Maurice M. Ohayon reports a relationship with Jazz Pharmaceuticals that includes: consulting or advisory. Colin M. Shapiro reports a relationship with Avadel Pharmaceuticals that includes: consulting or advisory and speaking and lecture fees. Colin M. Shapiro reports a relationship with 10.13039/100011096Jazz Pharmaceuticals that includes: consulting or advisory and speaking and lecture fees. Jennifer Gudeman reports a relationship with Avadel Pharmaceuticals that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Once-nightly sodium oxybate (ON-SXB), an extended-release oxybate formulation, yielded significant ( P  < 0.001 at 6 g, 7.5 g, and 9 g) reductions in cataplexy episodes in participants in the phase 3 REST-ON clinical trial (NCT02720744). This post hoc analysis from REST-ON further characterized changes in cataplexy episodes in participants with narcolepsy type 1 (NT1)., Methods: Participants with narcolepsy aged ≥16 years received ON-SXB (1 wk, 4.5 g; 2 wk, 6 g; 5 wk, 7.5 g; 5 wk, 9 g) or placebo. Percentages of participants with NT1 who had ≥25%, ≥50%, ≥75%, and 100% reductions from baseline in mean number of weekly cataplexy episodes were determined. Two-sided P values comparing ON-SXB vs placebo were calculated with Fisher exact test., Results: Participants with NT1 (ON-SXB, n = 73; placebo, n = 72; modified intent-to-treat population) had a baseline mean number of weekly cataplexy episodes of 18.9 (ON-SXB) and 19.8 (placebo). Of participants receiving the highest doses of ON-SXB (7.5 and 9 g), approximately half had a 50% reduction, one-third had a 75% reduction, and one-tenth had a 100% reduction in their cataplexy episodes vs placebo. Significantly greater proportions of participants receiving ON-SXB vs placebo had respective reductions in weekly cataplexy episodes of ≥25% at weeks 1 (4.5 g; P  < 0.05), 3 (6 g; P  < 0.001), 8 (7.5 g; P  < 0.001), and 13 (9 g; P  = 0.001)., Conclusions: A significantly greater proportion of participants receiving ON-SXB vs placebo experienced reductions in weekly cataplexy episodes at all tested doses. Approximately 10% of participants taking the 2 highest ON-SXB doses had complete elimination of their cataplexy., Competing Interests: Michael J. Thorpy reports a relationship with Axsome Therapeutics Inc that includes: consulting or advisory. Michael J. Thorpy reports a relationship with Balance Therapeutics that includes: consulting or advisory. Michael J. Thorpy reports a relationship with Eisai that includes: consulting or advisory. Michael J. Thorpy reports a relationship with Avadel Pharmaceuticals that includes: consulting or advisory. Michael J. Thorpy reports a relationship with Harmony Biosciences that includes: consulting or advisory. Michael J. Thorpy reports a relationship with Jazz Pharmaceuticals that includes: consulting or advisory. Michael J. Thorpy reports a relationship with NLS Pharmaceuticals that includes: consulting or advisory. Michael J. Thorpy reports a relationship with Suven Life Sciences Ltd. that includes: consulting or advisory. Michael J. Thorpy reports a relationship with Takeda Pharmaceutical Co that includes: consulting or advisory. Clete A. Kushida reports a relationship with Avadel Pharmaceuticals that includes: consulting or advisory. Clete A. Kushida reports a relationship with XW Pharma that includes: consulting or advisory. Richard Bogan reports a relationship with WaterMark Medical and Healthy Humming, LLC that includes: equity or stocks. Richard Bogan reports a relationship with WaterMark Medical that includes: board membership. Richard Bogan reports a relationship with 10.13039/100011096Jazz Pharmaceuticals that includes: consulting or advisory, funding grants, and speaking and lecture fees. Richard Bogan reports a relationship with 10.13039/100007723Takeda Pharmaceutical Co. that includes: consulting or advisory and funding grants. Richard Bogan reports a relationship with Avadel Pharmaceuticals that includes: consulting or advisory and funding grants. Richard Bogan reports a relationship with Oventus that includes: consulting or advisory. Richard Bogan reports a relationship with BresoTec that includes: funding grants. Richard Bogan reports a relationship with 10.13039/100004326Bayer that includes: funding grants. Richard Bogan reports a relationship with 10.13039/501100016198Idorsia that includes: funding grants. Richard Bogan reports a relationship with Suven Life Sciences Ltd that includes: funding grants. Richard Bogan reports a relationship with Balance that includes: funding grants. Richard Bogan reports a relationship with 10.13039/100010902Vanda that includes: funding grants. Richard Bogan reports a relationship with 10.13039/100004334Merck & Co., Inc that includes: funding grants. Richard Bogan reports a relationship with 10.13039/501100003769Eisai that includes: funding grants and speaking and lecture fees. Richard Bogan reports a relationship with 10.13039/100004320Philips that includes: funding grants. Richard Bogan reports a relationship with FRESCA Medical that includes: funding grants. Richard Bogan reports a relationship with 10.13039/100013410LivaNova that includes: funding grants. Richard Bogan reports a relationship with 10.13039/100004337Roche that includes: funding grants. Richard Bogan reports a relationship with Sommetrics that includes: funding grants. Richard Bogan reports a relationship with Harmony Biosciences that includes: speaking and lecture fees. Akinyemi O. Ajayi reports a relationship with Avadel Pharmaceuticals that includes: consulting or advisory. Bruce C. Corser reports a relationship with 10.13039/100011096Jazz Pharmaceuticals that includes: speaking and lecture fees. Bruce C. Corser reports a relationship with 10.13039/100004334Merck & Co., Inc that includes: speaking and lecture fees. Bruce C. Corser reports a relationship with 10.13039/501100003769Eisai that includes: speaking and lecture fees. Bruce C. Corser reports a relationship with Harmony Biosciences that includes: speaking and lecture fees. Bruce C. Corser reports a relationship with Avadel Pharmaceuticals that includes: consulting or advisory and speaking and lecture fees. Jennifer Gudeman reports a relationship with Avadel Pharmaceuticals that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Many people worldwide experience obstructive sleep apnea, which is associated with medical and psychological problems. Continuous positive airway pressure (CPAP) is an efficacious therapy for obstructive sleep apnea, but its effect is limited by nonadherence. Studies show that personalized education and feedback can increase CPAP adherence. Moreover, tailoring the style of information to the psychological profile of a patient has been shown to enhance the impact of interventions., Objective: This study aimed to assess the effect of an intervention providing digitally generated personalized education and feedback on CPAP adherence and the additional effect of tailoring the style of the education and feedback to an individual's psychological profile., Methods: This study was a 90-day, multicenter, parallel, single-blinded, and randomized controlled trial with 3 conditions: personalized content in a tailored style (PT) in addition to usual care (UC), personalized content in a nontailored style (PN) in addition to UC, and UC. To test the effect of personalized education and feedback, the PN + PT group was compared with the UC group. To test the additional effect of tailoring the style to psychological profiles, the PN and PT groups were compared. Overall, 169 participants were recruited from 6 US sleep clinics. The primary outcome measures were adherence based on minutes of use per night and on nights of use per week., Results: We found a significant positive effect of personalized education and feedback on both primary adherence outcome measures. The difference in the estimated average adherence based on minutes of use per night between the PT + PN and UC groups on day 90 was 81.3 minutes in favor of the PT + PN group (95% CI -134.00 to -29.10; P=.002). The difference in the average adherence based on nights of use per week between the PT + PN and UC groups at week 12 was 0.9 nights per week in favor of the PT + PN group (difference in odds ratio 0.39, 95% CI 0.21-0.72; P=.003). We did not find an additional effect of tailoring the style of the intervention to psychological profiles on the primary outcomes. The difference in nightly use between the PT and PN groups on day 90 (95% CI -28.20 to 96.50; P=.28) and the difference in nights of use per week between the PT and PN groups at week 12 (difference in odds ratio 0.85, 95% CI 0.51-1.43; P=.054) were both nonsignificant., Conclusions: The results show that personalized education and feedback can increase CPAP adherence substantially. Tailoring the style of the intervention to the psychological profiles of patients did not further increase adherence. Future research should investigate how the impact of interventions can be enhanced by catering to differences in psychological profiles., Trial Registration: ClinicalTrials.gov NCT02195531; https://clinicaltrials.gov/ct2/show/NCT02195531., (©Joyca Lacroix, Jan Tatousek, Niek Den Teuling, Thomas Visser, Charles Wells, Paul Wylie, Russell Rosenberg, Richard Bogan. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 22.05.2023.)

Obstructive sleep apnea (OSA), a disease associated with excessive sleepiness and increased cardiovascular risk, affects an estimated 1 billion people worldwide. The present study examined proteomic biomarkers indicative of presence, severity, and treatment response in OSA. Participants (n = 1391) of the Stanford Technology Analytics and Genomics in Sleep study had blood collected and completed an overnight polysomnography for scoring the apnea−hypopnea index (AHI). A highly multiplexed aptamer-based array (SomaScan) was used to quantify 5000 proteins in all plasma samples. Two separate intervention-based cohorts with sleep apnea (n = 41) provided samples pre- and post-continuous/positive airway pressure (CPAP/PAP). Multivariate analyses identified 84 proteins (47 positively, 37 negatively) associated with AHI after correction for multiple testing. Of the top 15 features from a machine learning classifier for AHI ≥ 15 vs. AHI < 15 (Area Under the Curve (AUC) = 0.74), 8 were significant markers of both AHI and OSA from multivariate analyses. Exploration of pre- and post-intervention analysis identified 5 of the 84 proteins to be significantly decreased following CPAP/PAP treatment, with pathways involving endothelial function, blood coagulation, and inflammatory response. The present study identified PAI-1, tPA, and sE-Selectin as key biomarkers and suggests that endothelial dysfunction and increased coagulopathy are important consequences of OSA, which may explain the association with cardiovascular disease and stroke.

The purpose of this study was to elucidate the differentiating or grouping EEG characteristics in various hypersomnias (type 1 and type 2 narcolepsy (N-1 and N-2) and idiopathic hypersomnia (IH) compared to an age-matched snoring reference group (SR). Polysomnogram sleep EEG was decomposed into a 4-frequency state model. The IH group had higher sleep efficiency (SE; 92.3% vs. 85.8%; sp < 0.05), lower WASO (IH = 35.4 vs. N-1 = 65.5 min; p < 0.01), but similar (i.e. high) arousal indices as N-1 (~33/h). N-1 and N-2 had earlier REM latency than IH and SR (N-1 = 64.8, N-2 = 76.3 vs. IH/SR = 118 min, p < 0.05). N-1 and N-2 showed an increase in MF1 segments (characteristic of stage 1 and REM) across the night as well as distinct oscillations every 2 h, but MF1 segment timing was advanced by 30 min compared to the SR group (p < 0.05). This suggests the presence of circadian organization to sleep that is timed earlier or of increased pressure and/or lability. MF1 demonstrated a mixed phenotype in IH, with an early 1 st oscillation (like N-1 and N-2), 2 nd oscillation that overlapped with the SR group, and a surge prior to wake (higher than all groups). This phenotype may reflect a heterogeneous group of individuals, with some having more narcolepsy-like characteristics (i.e. REM) than others. LF domain (delta surrogate) was enhanced in IH and N-1 and more rapidly dissipated compared to N-2 and SR (p < 0.05). This suggests an intact homeostatic sleep pattern that is of higher need/reduced efficiency whereas rapid dissipation may be an underlying mechanism for sleep disruption.

Introduction: The present post hoc analysis was designed to evaluate health-related quality of life (HRQoL) using the 36-item Short Form Health Status Survey (SF-36) during an 8-week trial of sodium oxybate (SXB)., Methods: SF-36 was assessed in a phase 3 placebo-controlled trial in patients with narcolepsy (N = 228) randomized to placebo or SXB in doses of 4.5, 6, or 9 g nightly for 8 weeks. Changes from baseline in SF-36 (last observation carried forward) were compared between SXB and placebo, and effect sizes (ES) were estimated., Results: Baseline SF-36 values were lower than normative values for the US general population. After 8 weeks of treatment, mean (±standard deviation) improvement from baseline on the Physical Component Summary (PCS) was significantly greater with SXB 9 g/night than placebo (6.3 ± 9.1 vs. 1.5 ± 6.2; p = 0.005), with moderate ES; no significant difference was found between the SXB and placebo groups on the Mental Component Summary. SXB 9 g/night resulted in significantly (p < 0.05) greater improvements than placebo in Physical Functioning (4.4 ± 9.2 vs. 1.0 ± 8.0), General Health (GH; 3.1 ± 7.0 vs. 0.4 ± 6.8), and Social Functioning (6.8 ± 16.8 vs. 1.1 ± 9.6). All SXB doses resulted in significant improvement (p < 0.05) relative to placebo for Vitality, with moderate ES. No significant differences versus placebo were observed for Role-Physical, Role-Emotional, or Mental Health domains., Conclusion: Treatment with SXB was associated with a dose-dependent improvement in HRQoL, with the 9-g nightly dose demonstrating a positive impact on PCS and individual SF-36 domains of Vitality, GH, and Physical and Social Functioning., Trial Registration: NCT00049803., Funding: Jazz Pharmaceuticals.

Study Objectives: To address some of the questions about "who" has been tested for OSA (in terms of pretest risk and study outcomes) using a leading national portable recorder (PR; "home sleep test")., Design: This was a retrospective analysis of a large repository of de-identified test results and pretest OSA risk from 2009 to 2013., Setting and Patients: A total of 244,602 patients were referred for testing from a variety of clinical practices across North America. A total of 193,221 studies were included in the final analyses., Interventions: NA., Measurements and Results: The final sample was predominately male (59%), middle-aged (53.5 ± 14.2 years), obese (BMI >30; 54%), with a large neck circumference (males = 16.9 ± 1.2 in; females = 15.0 ± 1.3 in) and a mild degree of reported sleepiness (ESS 8.7±5.3). Approximately 50% of the sample endorsed a history of hypertension. The majority of patients (89.6%) were at a high risk for OSA as assessed by the ARES screening questionnaire. Of this group, 79.9% had an AHI ≥5 (MAHI = 18.2 ± 18.1) and 98% had an RDI ≥5 (MRDI = 28.0 ± 19.6). The majority of patients (~60%) that screened at no apparent risk for OSA indeed had AHIs <5 events/h. Those with a high pretest risk for OSA but low test outcomes (AHI <5) were twice as likely to be female and approximately 20% to 30% more likely to report a history of insomnia, lung disease, and/or stroke., Conclusions: The majority of PR has been conducted on patients with a high degree of suspicion for OSA. These data suggest that PR has been used in patients with a high pretest probability of OSA. Patients with a history of insomnia, stroke, and/ or lung disease may especially benefit by a comprehensive evaluation by a physician trained in sleep medicine, especially if PR results are negative for OSA. Future studies should evaluate the utility of gender-appropriate screening measures. Although questionnaire-based screening is helpful in determining OSA risk, it is imperative that it be used in conjunction with clinical decision-making., (© 2014 American Academy of Sleep Medicine.)

Osteogenesis imperfecta type VI (OI type VI) has recently be linked to a mutation in the SERPINF1 gene, which encodes pigment epithelium-derived factor (PEDF), a ubiquitously expressed protein originally described for its neurotrophic and antiangiogenic properties. In this study, we characterized the skeletal phenotype of a mouse with targeted disruption of Pedf. In normal mouse bone, Pedf was localized to osteoblasts and osteocytes. Micro-computed tomography (µCT) and quantitative bone histomorphometry in femurs of mature Pedf null mutants revealed reduced trabecular bone volume and the accumulation of unmineralized bone matrix. Fourier transform infrared microscopy (FTIR) indicated an increased mineral:matrix ratio in mutant bones, which were more brittle than controls. In vitro, osteoblasts from Pedf null mice exhibited enhanced mineral deposition as assessed by Alizarin Red staining and an increased mineral:matrix determined by FTIR analysis of calcified nodules. The findings in this mouse model mimic the principal structural and biochemical features of bone observed in humans with OI type VI and consequently provide a useful model with which to further investigate the role of PEDF in this bone disorder., (Copyright © 2013 American Society for Bone and Mineral Research.)

The factors and processes involved in regression of the primate corpus luteum (CL) are complex and not fully understood. Systemic identification of those genes that are differentially expressed utilizing macaque model systems of luteal regression could help clarify some of the important molecular events involved in loss of primate luteal structure and function during luteolysis. In addition, examining gene pathways involved in luteal regression may help elucidate novel approaches for overcoming infertility or designing ovary-based contraceptives. This review provides an overview of the current published microarray experiments evaluating the transcriptome of the macaque CL, and compares and contrasts the data from spontaneous, GnRH antagonist and prostaglandin F2α-induced luteal regression. In addition, further uses of these databases are discussed, as well as limitations of both array technology and the rhesus macaque genome array.

Background: Parthenogenetic embryonic stem cells (PESCs) may have future utilities in cell replacement therapies since they are closely related to the female from which the activated oocyte was obtained. Furthermore, the avoidance of parthenogenetic development in mammals provides the most compelling rationale for the evolution of genomic imprinting, and the biological process of parthenogenesis raises complex issues regarding differential gene expression., Methods and Results: We describe here homozygous rhesus monkey PESCs derived from a spontaneously duplicated, haploid oocyte genome. Since the effect of homozygosity on PESCs pluripotency and differentiation potential is unknown, we assessed the similarities and differences in pluripotency markers and developmental potential by in vitro and in vivo differentiation of homozygous and heterozygous PESCs. To understand the differences in gene expression regulation between parthenogenetic and biparental embryonic stem cells (ESCs), we conducted microarray analysis of genome-wide mRNA profiles of primate PESCs and ESCs derived from fertilized embryos using the Affymetrix Rhesus Macaque Genome array. Several known paternally imprinted genes were in the highly down-regulated group in PESCs compared with ESCs. Furthermore, allele-specific expression analysis of other genes whose expression is also down-regulated in PESCs, led to the identification of one novel imprinted gene, inositol polyphosphate-5-phosphatase F (INPP5F), which was exclusively expressed from a paternal allele., Conclusion: Our findings suggest that PESCs could be used as a model for studying genomic imprinting, and in the discovery of novel imprinted genes.

Excessive sleepiness (ES) is a widespread condition, commonly the result of a sleep/ wake disorder such as obstructive sleep apnea (OSA), shift-work disorder (SWD), or narcolepsy. ES poses significant health and safety concerns in patients. Numerous interventions are available to treat the underlying causes of ES and ES itself, including behavioral measures, mechanical devices, and pharmacologic agents. This review explores the evidence supporting the use of armodafinil to treat ES associated with OSA, SWD, and narcolepsy. Armodafinil is an oral non-amphetamine wake-promoting agent, the R-isomer of racemic modafinil. Armodafinil and modafinil share many clinical and pharmacologic properties and are distinct from central nervous system stimulants; however, the mechanisms of action of modafinil and armodafinil are poorly characterized. Compared with modafinil, the wake-promoting effects of armodafinil persist later in the day. It is for this reason that armodafinil may be a particularly appropriate therapy for patients with persistent ES due to OSA, SWD, or narcolepsy.