Obstructive sleep apnea is associated with risk for sudden unexpected death in epilepsy (SUDEP) using rSUDEP-7.

BACKGROUND AND OBJECTIVE: Evaluate relationships between PSG-confirmed OSA and SUDEP risk using the revised SUDEP Risk Inventory (rSUDEP-7). METHODS: Identified adults with epilepsy (AWE) who underwent PSG 2004-2016 at Cleveland Clinic. OSA was defined as apnea-hypopnea index (AHI)- ≥-5/h sleep; moderate/severe OSA as AHI≥15. SUDEP risk was assessed using rSUDEP-7: higher rSUDEP-7 score, greater SUDEP risk. Associations between rSUDEP-7 score and OSA groups (AHI≥15 vs. <15) were evaluated using Wilcoxon rank-sum tests and multivariable linear models adjusting for age, sex, BMI, and smoking status. Spearman correlations measured relationships between rSUDEP-7 score with AHI and oxygen desaturation indices (ODI). RESULTS: OSA was present in 134 (62.6 %) of 214 AWE; moderate/severe in 75 (35 %). AWE with AHI≥15 were more likely to be male and older, had higher BMI, greater frequency of tonic-clonic seizures (TCS), longer epilepsy duration, and more likely to have drug-resistant epilepsy (DRE) and sleep-related seizures (all p< 0.05). The median rSUDEP-7 score was 1 (0,3) but 37.4 % had a score ≥3 (high SUDEP risk), and 11.7 % ≥5 (highest SUDEP risk). rSUDEP-7 scores were higher in those with AHI≥15 (3 vs. 1, p = 0.001). Higher AHI and ODI 3% positively correlated with rSUDEP-7 (p=0.002 and p=0.016) while SpO2 nadir negatively correlated with rSUDEP-7 (p=0.007). After adjustments, AWE with AHI≥15 had mean rSUDEP-7 score 1.14 points (95% CI 0.55-1.72, p<0.001) higher than those with AHI<15. DISCUSSION: AWE with PSG-confirmed moderate/severe OSA especially those who are older and have GTC had higher rSUDEP-7 scores potentially increasing their risk for SUDEP. Our findings support routine screening for OSA in AWE. Further studies confirming the significance and impact of OSA on SUDEP risk are needed.

Who Should Talk to Patients and How About Whether They Have Access to Sufficient, Quality Sleep?

Primary care clinicians are well-equipped to screen for sleep concerns, help some patients, and refer patients whose sleep troubles are more complex to specialists. Poor sleep affects nearly every organ system and influences many morbidity and mortality causes, so screening for sleep sufficiency and quality should be prioritized in primary care settings. This commentary on a case suggests strategies for more fully supporting primary care clinicians' compensation and capacity for conducting effective conversations with patients experiencing sleep trouble.

Sleep disorders associated with cranial radiation - a systematic review.

BACKGROUND: Radiation is standard-of-care treatment for primary brain tumors but may have profound effects on sleep that have not yet been fully characterized. This systematic review aims to further our understanding of radiation therapy on risk of development of sleep disorders in patients with primary brain tumors (PBTs), as well as potential opportunities for prevention and treatment. METHODS: A systematic search of PubMed, Embase, and Web of Science was performed (last Jan 2024) with predefined inclusion (PBT patients, radiation therapy, somnolence/circadian disruption) and exclusion (reviews/abstracts/cases/chapters, non-PBT cancer, lack of radiation) criteria, yielding 267 papers initially and 38 studies included. Data extraction and analysis (descriptive statistics, individual study summary) focused on incidence of sleep disturbances, radiation types/doses, and pharmacologic interventions. Risk of bias assessment was conducted with Effective Public Health Practice Project's Quality Assessment Tool for Quantitative Studies. RESULTS: The included 38 studies (n=2948 patients) demonstrated high incidence of sleep disturbances in patients with primary brain tumors throughout radiation therapy, but primarily from the end of radiation to 6 months after. Sleep symptoms were associated with radiation (dose-dependent), and pharmacotherapies were helpful in patients with formal sleep disorder diagnoses. Terminology and incidence reporting of sleep symptoms are inconsistent, and many studies had high risk of bias. CONCLUSIONS: This systematic review highlights the ongoing challenges with sleep symptoms/disorders related to cranial irradiation treatment in the primary brain tumor population. Further investigations on the interconnectedness of sleep disturbance constructs and possible pharmacotherapies to alleviate symptoms are warranted.

Perceptions of Lactation Experience Among Neurology Faculty and Impact of Lactation Time on Academic Achievement at U.S. Academic Medical Centers.

Objective: To investigate the perceptions of lactation experiences of neurology faculty and the impact of lactation time on academic achievement. Materials and Methods: This was a cross-sectional study utilizing a survey administered across 19 academic neurology centers in the United States. Respondents self-identified as having children and answered questions about lactation at work. Demographic information; academic achievement including publications, guest speakerships, awards, leadership roles, and funding; and perception of lactation experience were analyzed. Results: Among 162 respondents, 83% took lactation time at work. Thirty-seven percent reported lack of employer support for lactation, 46% were dissatisfied with their lactation experience, 59% did not receive compensation for lactation time, 62% did not have blocked clinical time, 73% reported relative value units were not adjusted to accommodate lactation, and 43% reported lack of access to private lactation space. Women spent on average 9.5 months lactating per child and desired 2.4 further months of lactation. There was no difference in all measures of self-reported academic achievement between women who did and did not take lactation time when measured across all career stages. Conclusions: Although a majority of respondents took lactation time at work, perceptions of employer support for lactation were low, and expectations for work productivity were not adjusted to accommodate lactation time. Taking lactation time at work did not decrease self-reported academic achievement. System-level best practices designed to support lactating faculty should be developed to guide academic institutions.

Real world challenges and barriers for positive airway therapy use in acute ischemic stroke patients.

PURPOSE: Untreated obstructive sleep apnea (OSA) in patients with acute ischemic stroke (AIS) is associated with increased morbidity and mortality. However, diagnosing and treating OSA in AIS is challenging. We aimed to determine the feasibility of portable monitoring (PM) for diagnosis and positive airway pressure therapy for treatment of OSA in an inpatient stroke population. METHODS: We recruited inpatients with AIS from Cleveland Clinic. Those who consented underwent PM; participants with a respiratory event index (REI) ≥ 10 were offered auto-titrating positive airway pressure therapy (APAP). Ease-of-use questionnaires were completed. We summarized categorical variables using n(%) and continuous variables using mean ± SD or median [IQR]. RESULTS: 27 participants (age 59.8 ± 11.8, 51.9% female, 51.9% Black, BMI 33.4 ± 8.5) enrolled. The study ended early due to Medicare contracting that forced most patients to complete stroke rehabilitation outside the Cleveland Clinic health system. 59.3% had large vessel occlusions and 53.8% had moderate/severe disability (Modified Rankin score ≥ 2). PM was attempted in 21 participants, successful in 18. Nurses and patients rated the PM device as highly easy to use. 13 of 18 (72%) patients who had an REI ≥ 10 consented to APAP titration, but only eight (61.5%) of those 13 used APAP for more than one night, and only five (27.8%) used APAP up to 90 days with data captured for only one participant. Five required troubleshooting at titration, and only one had adherent APAP usage by objective assessment after discharge. CONCLUSIONS: This study demonstrates the real-world challenges of assessing and treating OSA in an AIS population, highlighting the necessity for further research into timely and feasible screening and treatment.

Novel Sleep Phenotypic Profiles Associated With Incident Atrial Fibrillation in a Large Clinical Cohort.

BACKGROUND: While sleep disorders are implicated in atrial fibrillation (AF), the interplay of physiologic alterations and symptoms remains unclear. Sleep-based phenotypes can account for this complexity and translate to actionable approaches to identify at-risk patients and therapeutic interventions. OBJECTIVES: This study hypothesized discrete phenotypes of symptoms and polysomnography (PSG)-based data differ in relation to incident AF. METHODS: Data from the STARLIT (sleep Signals, Testing, And Reports LInked to patient Traits) registry on Cleveland Clinic patients (≥18 years of age) who underwent PSG from November 27, 2004, to December 30,2015, were retrospectively examined. Phenotypes were identified using latent class analysis of symptoms and PSG-based measures of sleep-disordered breathing and sleep architecture. Phenotypes were included as the primary predictor in a multivariable-adjusted Cox proportional hazard models for incident AF. RESULTS: In our cohort (N = 43,433, age 51.8 ± 14.5 years, 51.9% male, 74.9% White), 7.3% (n = 3,166) had baseline AF. Over a 7.6- ± 3.4-year follow-up period, 8.9% (n = 3,595) developed incident AF. Five phenotypes were identified. The hypoxia subtype (n = 3,245) had 48% increased incident AF (HR: 1.48; 95% CI: 1.34-1.64), the apneas + arousals subtype (n = 4,592) had 22% increased incident AF (HR: 1.22; 95% CI: 1.10-1.35), and the short sleep + nonrapid eye movement subtype (n = 6,126) had 11% increased incident AF (HR: 1.11; 95% CI: 1.01-1.22) compared with long sleep + rapid eye movement (n = 26,809), the reference group. The hypopneas subtype (n = 2,661) did not differ from reference (HR: 0.89; 95% CI: 0.77-1.03). CONCLUSIONS: Consistent with prior evidence supporting hypoxia as an AF driver and cardiac risk of the sleepy phenotype, this constellation of symptoms and physiologic alterations illustrates vulnerability for AF development, providing potential value in enhancing our understanding of integrated sleep-specific symptoms and physiologic risk of atrial arrhythmogenesis.

Analysis of Faculty Gender and Race in Scholarly Achievements in Academic Neurology.

Background: Intersection of gender and race and/or ethnicity in academic medicine is understudied; we aim to understand these factors in relation to scholarly achievements for neurology faculty. Methods: Faculty from 19 US neurology departments completed a survey (2021-2022) to report rank, leadership positions, publications, funded projects, awards, and speaker invitations. Regression analyses examined effects of gender, race, and their intersectionality on these achievements. Women, Black/Indigenous/People of Color (BIPOC), and BIPOC women were comparator groups. Results: Four hundred sixty-two faculty responded: 55% women, 43% men; 31% BIPOC, 63% White; 21% BIPOC women, 12% BIPOC men, 36% White women, 31% White men. Men and White faculty are more likely to be full professors than women and BIPOC faculty. The number of leadership positions, funded projects, awards, and speaker invitations are significantly greater in White compared to BIPOC faculty. Relative to BIPOC women, the number of leadership positions is significantly higher among BIPOC men, White women, and White men. Publication numbers for BIPOC men are lower, number of funded projects and speaker invitations for White women are higher, and number of awards among White men and White women is higher compared to BIPOC women. Discussion: Our study highlights that inequities in academic rank, award number, funded projects, speakership invitations, and leadership roles disproportionately impacted BIPOC women. More studies are needed to evaluate gender and race and/or ethnicity intersectionality effects on faculty achievements, reasons for inequities, recognition, and potential solutions.

Chronotype variability in epilepsy and clinical significance: scoping review.

PURPOSE: Chronotype, which captures a person's daily preferences for activity and sleep, is still a poorly researched area in epilepsy research. Finding common chronotype characteristics in people with epilepsy (PWE) and explaining possible effects on seizure management are the main goals. METHODS: Eleven large-scale investigations from 2010 to 2023 were examined in this scoping review. These studies included 1.167 PWE and 4.657 control subjects. RESULTS: PWE had intermediate chronotypes more often than not. Adult patients were more morning-oriented overall, while pediatric cohorts were variable. Relationships between chronotype and seizure control were limited since only two studies in adults reported this and those results conflicted. An evening-type chronotype was found to be more common in generalized epilepsy than focal. The relationship of chronotype and specific antiseizure medication (ASM) therapy was not investigated. CONCLUSIONS: The majority of PWE displayed an intermediate chronotype, but analyses based on age showed more nuanced trends, with children displaying variable patterns, adults generally tending toward morningness, and generalized epilepsy being associated with eveningness. This review underscores the importance of more research on the complex connections between epilepsy outcomes and chronotype. It emphasizes the need to study larger samples of PWE with carefully documented seizure control and ASM therapy, including dose and timing of administration to better understand the role of chronotype on epilepsy outcomes.

Adverse Cardiovascular Outcomes in Patients With Obstructive Sleep Apnea and Obesity: Metabolic Surgery vs Usual Care.

BACKGROUND: No therapy has been shown to reduce the risk of major adverse cardiovascular events (MACE) and death in patients with obstructive sleep apnea (OSA). OBJECTIVES: The authors sought to investigate the long-term relationship between metabolic surgery and incident MACE in patients with OSA and obesity. METHODS: Adult patients with a body mass index 35 to 70 kg/m2 and moderate-to-severe OSA at a U.S. health system (2004-2018) were identified. Baseline characteristics of patients who underwent metabolic surgery were balanced with a nonsurgical control group using overlap-weighting methods. Multivariable Cox regression analysis estimated time-to-incident MACE. Follow-up ended in September 2022. RESULTS: A total of 13,657 patients (7,496 [54.9%] men; mean age 52.0 ± 12.4 years; median body mass index 41.0 kg/m2 [Q1-Q3: 37.6-46.2 kg/m2]), including 970 patients in the metabolic surgery group and 12,687 patients in the nonsurgical group, with a median follow-up of 5.3 years (Q1-Q3: 3.1-8.4 years) were analyzed. The mean between-group difference in body weight at 10 years was 26.6 kg (95% CI: 25.6-27.6 kg) or 19.3% (95% CI: 18.6%-19.9%). The 10-year cumulative incidence of MACE was 27.0% (95% CI: 21.6%-32.0%) in the metabolic surgery group and 35.6% (95% CI: 33.8%-37.4%) in the nonsurgical group (adjusted HR: 0.58 [95% CI: 0.48-0.71]; P < 0.001). The 10-year cumulative incidence of all-cause mortality was 9.1% (95% CI: 5.7%-12.4%) in the metabolic surgery group and 12.5% (95% CI: 11.2%-13.8%) in the nonsurgical group (adjusted HR: 0.63 [95% CI: 0.45-0.89]; P = 0.009). CONCLUSIONS: Among patients with moderate-to-severe OSA and obesity, metabolic surgery, compared with nonsurgical management, was associated with a significantly lower risk of incident MACE and death.

Clinical considerations in the treatment of idiopathic hypersomnia.

Idiopathic hypersomnia typically is a chronic and potentially debilitating neurologic sleep disorder, and is characterized by excessive daytime sleepiness. In addition to excessive daytime sleepiness, idiopathic hypersomnia symptoms can include severe sleep inertia; long, unrefreshing naps; long sleep time; and cognitive dysfunction. Patients with idiopathic hypersomnia may experience a significant impact on their quality of life, work or school performance, earnings, employment, and overall health. Given the complex range of symptoms associated with idiopathic hypersomnia and the array of treatments available, there is a need to provide guidance on the treatment of idiopathic hypersomnia and the clinically relevant recommendations that enhance effective disease management. Identifying appropriate treatment options for idiopathic hypersomnia requires timely and accurate diagnosis, consideration of individual patient factors, and frequent reassessment of symptom severity. In 2021, low-sodium oxybate was the first treatment to receive approval by the US Food and Drug Administration for the treatment of idiopathic hypersomnia in adults. However, many off-label treatments continue to be used. Adjunct nonpharmacologic therapies, including good sleep hygiene, patient education and counseling, and use of support groups, should be recognized and recommended when appropriate. This narrative review describes optimal treatment strategies that take into account patient-specific factors, as well as the unique characteristics of each medication and the evolution of a patient's response to treatment. Perspectives on appropriate symptom measurement and management, and potential future therapies, are also offered.

Sleep-Disordered Breathing, Hypoxia, and Pulmonary Physiologic Influences in Atrial Fibrillation.

Background We leverage a large clinical cohort to elucidate sleep-disordered breathing and sleep-related hypoxia in incident atrial fibrillation (AF) development given the yet unclear contributions of sleep-related hypoxia and pulmonary physiology in sleep-disordered breathing and AF. Methods and Results Patients who underwent sleep studies at Cleveland Clinic January 2, 2000, to December 30, 2015, comprised this retrospective cohort. Cox proportional hazards models were used to examine apnea hypopnea index, percentage time oxygen saturation <90%, minimum and mean oxygen saturation, and maximum end-tidal carbon dioxide on incident AF adjusted for age, sex, race, body mass index, cardiopulmonary disease and risk factors, antiarrhythmic medications, and positive airway pressure. Those with spirometry were additionally adjusted for forced expiratory volume in 1 second, forced vital capacity, and forced expiratory volume in 1 second/forced vital capacity. This cohort (n=42 057) was 50.7±14.1 years, 51.3% men, 74.1% White individuals, had median body mass index 33.2 kg/m2, and 1947 (4.6%) developed AF over 5 years. A 10-unit apnea hypopnea index increase was associated with 2% higher AF risk (hazard ratio [HR], 1.02 [95% CI, 1.00-1.03]). A 10-unit increase in percentage time oxygen saturation <90% and 10-unit decreases in mean and minimum oxygen saturation were associated with 6% (HR, 1.06 [95% CI, 1.04-1.08]), 30% (HR, 1.30 [95% CI, 1.18-1.42]), and 9% (HR, 1.09 [95% CI, 1.03-1.15]) higher AF risk, respectively. After adjustment for spirometry (n=9683 with available data), only hypoxia remained significantly associated with incident AF, although all coefficients were stable. Conclusions Sleep-related hypoxia was associated with incident AF in this clinical cohort, consistent across 3 measures of hypoxia, persistent after adjustment for pulmonary physiologic impairment. Findings identify a strong role for sleep-related hypoxia in AF development without pulmonary physiologic interdependence.

Comparison of Databases for Complex Evidence Syntheses on Education for the Health Professions.

Increased requests for assistance with literature searches on educational topics within the health professions motivated two health science librarians to analyze search function and results in eleven bibliographic databases on questions representing three allied health instructional target populations (patient, caregiver, and future health professionals). Results overlap and relevance were estimated and useful functions and subject headings were examined, as evidence for future search and database recommendations. This research confirmed the authors' hypothesis that PubMed and CINAHL overlapped significantly yet yielded sufficient unique citations to recommend searching both, plus at least one education-specific database. For the six questions researched, psychology and sports medicine databases were less productive.

Long-term efficacy and safety of low-sodium oxybate in an open-label extension period of a placebo-controlled, double-blind, randomized withdrawal study in adults with idiopathic hypersomnia.

STUDY OBJECTIVES: To evaluate 6-month efficacy and safety of low-sodium oxybate in people with idiopathic hypersomnia during an open-label extension period (OLE) of a phase 3 clinical trial. METHODS: Efficacy measures included the Epworth Sleepiness Scale (ESS), Idiopathic Hypersomnia Severity Scale (IHSS), Patient Global Impression of Change (PGIc), Functional Outcomes of Sleep Questionnaire, short version (FOSQ-10), and Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP). Treatment-emergent adverse events were collected throughout the OLE. RESULTS: The OLE population included 106 participants. Most were female (71%) and White (83%), and the mean (SD) age was 41.0 (13.8) years. ESS scores decreased (improved) during the OLE (mean [SD], study baseline: 16.3 [2.8]; OLE week 2: 6.7 [4.7]; OLE end: 5.3 [3.7]), and IHSS total scores trended toward a decrease (study baseline: 32.6 [7.3]; OLE week 2: 16.2 [8.9]; OLE end: 14.8 [8.6]. Median (minimum, maximum) paired differences from OLE week 2 to OLE end were ESS, -1.0 (-20, 7; nominal P = .012); IHSS, -1.0 (-31, 19; nominal P = .086). The proportion of participants reporting PGIc ratings of "very much improved" increased from 36.7% at OLE week 2 to 53.8% at the OLE end. The FOSQ-10 and WPAI:SHP scores remained stable during OLE. The incidence of newly reported treatment-emergent adverse events decreased over the duration of the OLE. CONCLUSIONS: Efficacy and safety of low-sodium oxybate were maintained or improved during the 6-month OLE, supporting long-term treatment with low-sodium oxybate in adults with idiopathic hypersomnia. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: A Multicenter Study of the Efficacy and Safety of JZP-258 in the Treatment of Idiopathic Hypersomnia (IH) With an Open-label Safety Extension; URL: https://clinicaltrials.gov/study/NCT03533114; Identifier: NCT03533114 and Registry: EU Clinical Trials; Name: A Double-blind, Placebo-controlled, Randomized Withdrawal, Multicenter Study of the Efficacy and Safety of JZP-258 in the Treatment of Idiopathic Hypersomnia (IH) with an Open-label Safety Extension; URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-001311-79/results; Identifier: 2018-001311-79. CITATION: Morse AM, Dauvilliers Y, Arnulf I, et al. Long-term efficacy and safety of low-sodium oxybate in an open-label extension period of a placebo-controlled, double-blind, randomized withdrawal study in adults with idiopathic hypersomnia. J Clin Sleep Med. 2023;19(10):1811-1822.

Screening for cervical cancer among women with behavioral health conditions-A systematic review.

Cervical cancer screening is credited with dramatically reducing cervical cancer mortality in the United States. There is a lack of consensus on whether women with behavioral health conditions (mental health or substance use) receive cervical cancer screening at rates similar to women without the conditions. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we searched for articles and abstracts of conference proceedings in PubMed, EMBASE, Web of Science and the EBSCO databases: CINAHL, PsycINFO, Psychosocial and Behavioral Science Collection, Academic Search Premier Databases, and the ProQuest database Applied Social Sciences Index and Abstracts from January 1, 2000 to July 31, 2020. Eligibility criteria included studies conducted in the United States, published in English, and comparing cervical cancer screening rates of women with and without behavioral health conditions. Of 1,242 unique articles screened, 52 were included in the full text review. And after title/abstract/and full-text review, 14 articles met the eligibility criteria. Six studies examined both mental health and substance use conditions, two studies only examined substance use disorders, and six studies examined only mental health conditions. Substance use disorders were associated with a decreased likelihood of receiving screening. This study yeilded inconclusive findings on the relationship between mental health conditions and cervical cancer screening. More research is needed to better understand the relationship between behavioral health conditions and cervical cancer screening.

Librarian and Researcher Assessments of Search Result Relevance: How Well Do They Align?

Conducting comprehensive but efficient literature searches for complex evidence syntheses involves selecting databases that will retrieve the greatest number of relevant results on the question. Lack of a comprehensive single database on allied health educational topics challenges those seeking such literature. In this study, six participants contributed research questions on instructional methods and materials for allied health patients, caregivers, and future health professionals. Two health sciences librarians created search strategies for these questions and searched eleven databases. Both the librarians and the six participants evaluated the search results using a rubric based on PICO to assess extent of alignment between the librarians' and requestors' relevance judgments. Intervention, Outcome, and Assessment Method constituted the most frequent bases for assessments of relevance by both librarians and participants. The librarians were more restrictive in all of their assessments except in a preliminary search yielding twelve citations without abstracts. The study's results could be used to identify effective techniques for reference interviewing, selecting databases, and weeding search results.

Safety and pharmacodynamics of a single infusion of danavorexton in adults with idiopathic hypersomnia.

STUDY OBJECTIVES: Idiopathic hypersomnia (IH) is a chronic disorder characterized by excessive daytime sleepiness unexplained by another disorder or drug/medication use. Although the orexin system plays a role in sleep-wake regulation, orexin A levels in the cerebrospinal fluid are normal in people with IH. This phase 1b, randomized, placebo-controlled, crossover study aimed to investigate the safety, pharmacokinetics, and pharmacodynamics of danavorexton, a small-molecule orexin-2 receptor agonist, in adults with IH. METHODS: Adults with IH aged 18-75 years were randomized to one of two treatment sequences of single intravenous infusions of danavorexton 112 mg and placebo. Pharmacodynamic endpoints included the maintenance of wakefulness test (MWT), the Karolinska Sleepiness Scale (KSS), and the psychomotor vigilance task (PVT). Adverse events were monitored throughout the study period. RESULTS: Of 28 randomized participants, 12 (44.4%) had a treatment-emergent adverse event (TEAE) and 10 (37.0%) had a TEAE considered related to study drug, most of which were mild or moderate. Four participants (18.2%) had urinary TEAEs while receiving danavorexton, all of which were mild in severity. There were no deaths or TEAEs leading to discontinuation. Improvements in MWT, KSS, and PVT scores were observed with danavorexton compared to placebo. Following drug administration, a mean sleep latency of 40 min (maximum value) was observed during the MWT within 2 h of danavorexton infusion in most participants. CONCLUSIONS: A single infusion of danavorexton improves subjective and objective excessive daytime sleepiness in people with IH with no serious TEAEs, indicating orexin-2 receptor agonists are promising treatments for IH. Clinical Trial: Clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/NCT04091438.

Long-Term Safety and Tolerability During a Clinical Trial and Open-Label Extension of Low-Sodium Oxybate in Participants with Narcolepsy with Cataplexy.

BACKGROUND: The safety and efficacy of low-sodium oxybate (LXB; Xywav®) were established in a randomized, double-blind, placebo-controlled, phase 3 withdrawal study in adults with narcolepsy with cataplexy; however, the longer-term safety profile has not yet been examined. The aim of the current analysis was to assess the time of onset and duration of common treatment-emergent adverse events (TEAEs) for LXB throughout the open-label optimized treatment and titration period (OLOTTP) and the stable dose period (SDP) portions of the main study, and the subsequent 24-week open-label extension (OLE). METHODS: In a double-blind, placebo-controlled, randomized withdrawal trial of LXB, TEAEs were evaluated during the 12-week OLOTTP, the 2-week SDP, and the subsequent 24-week OLE. Eligible participants were aged 18-70 years with a diagnosis of narcolepsy with cataplexy. At study entry, participants were taking sodium oxybate (SXB) alone, SXB with other anticataplectics, other anticataplectics alone, or were anticataplectic-treatment naive; other anticataplectics were tapered and discontinued during the OLOTTP. All participants initiated LXB during week 1 of the OLOTTP, and their dose was individually titrated based on safety and efficacy. Following the main study period, participants entered the OLE after rescreening (re-entry) after discontinuing LXB treatment or directly after completing the main study (rollover). TEAEs were assessed in the safety population as of database lock. TEAE duration was defined as time from TEAE start date to end date (or end of SDP or OLE, if end date was unrecorded). RESULTS: The safety population included 201 participants (SXB alone, n = 52; SXB with other anticataplectics, n = 23; other anticataplectics alone, n = 36; anticataplectic-treatment naive, n = 90). During the OLOTTP/SDP, headache was the most common LXB-emergent TEAE overall (71 events; n = 42 (21%); median (range) duration = 1 (1-147) day), followed by nausea (31 events; n = 26 (13%); median (range) duration = 9 (1-54) days) and dizziness (26 events; n = 21 (10%); median (range) duration = 7 (1-117) days). Among the 74 participants in the OLE, the most commonly reported TEAEs were headache (14 events; n = 7, 9%; peak incidence month 3 (n = 5/72); median (range) duration = 1 (1‒25) day), dizziness (8 events; n = 5, 7%; peak incidence month 1 (n = 3/74); median (range) duration = 26 (1‒181) days), and nasopharyngitis (6 events; n = 6, 8%; peak incidence month 6 (n = 2/69); median (range) duration = 9 (1‒24) days). Overall, study discontinuations attributed to TEAEs were 21/65 (32%) during the OLOTTP and SDP and 3/7 (43%) during the OLE. CONCLUSIONS: In this long-term analysis, the safety and tolerability profile of LXB was generally consistent with the known safety profile of SXB. During the OLOTTP and SDP, most TEAEs occurred early and were generally of short duration. TEAE prevalence decreased throughout the duration of the OLE; the most common TEAEs reported during the OLE were headache, dizziness, and nasopharyngitis. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03030599 (25 January 2017).

Low-sodium oxybate (LXB) is a medicine for narcolepsy. LXB treats daytime sleepiness and cataplexy (sudden muscle weakness). LXB is like sodium oxybate (SXB) but has 92% less sodium. This study looked at side effects in people taking LXB for many months. Three study periods were looked at in this report. In period 1, people could change their LXB dose for 12 weeks. This was to find their best dose. In period 2, people took that same best dose for 2 weeks. In period 3, some people kept taking LXB for 24 weeks. This was to study the longer-term effects. Everyone knew that they were taking LXB. During periods 1 and 2, the most common side effect was headache. Nausea and dizziness were also common. During period 3, headache was also the most common side effect. Dizziness and nasopharyngitis were also common. Nasopharyngitis is a cold in the nose and throat. In periods 1 and 2, most side effects happened early on. They also ended quickly. Fewer side effects happened in period 3. Among people leaving the study early, 32% left because of side effects during periods 1 and 2. During period 3, 43% left because of side effects. Overall, long-term side effects in people taking LXB were similar to those seen with SXB.

Sex-specific differences in diagnostic approaches of inpatient sleep testing for obstructive sleep apnea.

BACKGROUND: Few studies have investigated sex-specific disparities in inpatient sleep testing. We postulate that women are more likely to have a milder degree of obstructive sleep apnea (OSA) and lower extent of hypoxia on Type III sleep studies versus polysomnography (PSG). PATIENTS AND METHODS: The Cleveland Clinic Sleep laboratory registry was leveraged to identify all adult inpatient sleep studies performed for OSA. Demographics, comorbidities, and sleep study measures were collected and compared by sex and sleep study type. Logistic regression was used to examine sleep study type predictive of OSA (apnea hypopnea index [AHI; ≥5, ≥15 and ≥ 30]) and hypoxia, (median percentage of sleep time spent at <90% SaO2 [TST<90%,≥ 11%,] adjusted for covariates. RESULTS: The sample 778 patients had a mean age of 56.1 ± 16.1 years; 44.5% were female and 72.2% Caucasian. At an AHI≥5, women showed an increase odds of OSA (adjusted, OR = 2.04,95%; CI:1.24-3.35, p = 0.005) with Type III sleep study vs PSG compared to men. At an AHI≥15, men had less odds of OSA (adjusted OR = 0.60,95%CI:0.39-0.90,p = 0.015) with Type III sleep study vs PSG compared to women (OR = 1.15,95%CI:0.72-1.85,p = 0.56), with an interaction p-value of 0.040. These results were attenuated when the analysis was restricted using the 3% hypopnea scoring rule. Men and women had higher odds of TST <90 ≥ 11% (OR:2.60,95%CI:1.60-4.21,p=<0.001; OR:3.46,95%CI:1.97-6.05,p < 0.001) with Type III sleep study versus PSG, albeit no sex-interaction was observed. CONCLUSIONS: These results suggest that sex-specific differences in diagnostic performance of sleep testing type in the inpatient setting should be considered according to level of OSA severity, which are influenced by hypopnea-related desaturation extent.