Improvement in sleep latency with extended-release once-nightly sodium oxybate for the treatment of adults with narcolepsy: Analysis from the phase 3 REST-ON clinical trial.

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.

Cataplexy response with extended-release once-nightly sodium oxybate: Post hoc responder analyses from the phase 3 REST-ON clinical trial.

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.

Sleep macro-architecture in patients with Parkinson's disease does not change during the first night of neurostimulation in a pilot study.

STUDY OBJECTIVES: A growing body of literature suggests that deep brain stimulation (DBS) to treat motor symptoms of Parkinson's disease (PD) may also ameliorate certain sleep deficits. Many foundational studies have examined the impact of stimulation on sleep following several months of therapy, leaving an open question regarding the time course for improvement. It is unknown whether sleep improvement will immediately follow onset of therapy or accrete over a prolonged period of stimulation. The objective of our study was to address this knowledge gap by assessing the impact of DBS on sleep macro-architecture during the first nights of stimulation. METHODS: Polysomnograms were recorded for three consecutive nights in 14 patients with advanced PD (10 male, 4 female; age: 53-74 years), with intermittent, unilateral subthalamic nucleus DBS on the final night or two. Sleep scoring was determined manually by a consensus of four experts. Sleep macro-architecture was objectively quantified using the percentage, latency, and mean bout length of wake after sleep onset (WASO) and on each stage of sleep (REM and NREM stages N1, N2, N3). RESULTS: Sleep was found to be highly disrupted in all nights. Sleep architecture on nights without stimulation was consistent with prior results in treatment naive patients with PD. No statistically significant difference was observed due to stimulation. CONCLUSIONS: These objective measures suggest that one night of intermittent subthreshold stimulation appears insufficient to impact sleep macro-architecture. CLINICAL TRIAL REGISTRATION: Name: Adaptive Neurostimulation to Restore Sleep in Parkinson's Disease; URL: https://clinicaltrials.gov/ct2/show/NCT04620551; Identifier: NCT04620551.

Endorsement of "European Respiratory Society guideline on non-CPAP therapies for obstructive sleep apnoea" by World Sleep Society.

Guidelines for management of sleep disorders from national or regional societies provide recommendations that may be regionally appropriate but may not always be practical or relevant in other parts of the world. A task force of experts from the World Sleep Society's (WSS) International Sleep Medicine Guidelines Committee and Sleep and Breathing Disorders Task Force reviewed the European Respiratory Society's guideline on non-CPAP therapies for obstructive sleep apnea (OSA) with respect to its relevance and applicability to the practice of sleep medicine by sleep specialists in various regions of the world. The task force and the WSS guidelines committee endorsed the European Respiratory Society's guideline with respect to the utilization of bariatric surgery, mandibular advancement devices, positioning devices, myofunctional therapy, hypoglossal neurostimulation, maxilo-mandibular surgery, and carbonic anhydrase inhibitors for the treatment of OSA. The task force and the WSS guidelines committee noted that there is substantial new evidence for the role of soft tissue, upper airway surgery, not included in the guidelines paper.

Proteomic insights into the pathophysiology of periodic limb movements and restless legs syndrome.

OBJECTIVES: We used a high-throughput assay of 5000 plasma proteins to identify biomarkers associated with periodic limb movements (PLM) and restless legs syndrome (RLS) in adults. METHODS: Participants (n = 1410) of the Stanford Technology Analytics and Genomics in Sleep (STAGES) study had blood collected, completed a sleep questionnaire, and underwent overnight polysomnography with the scoring of PLMs. An aptamer-based array (SomaScan) was used to quantify 5000 proteins in plasma. A second cohort (n = 697) that had serum assayed using a previous iteration of SomaScan (1300 proteins) was used for replication and in a combined analysis (n = 2107). A 5% false discovery rate was used to assess significance. RESULTS: Multivariate analyses in STAGES identified 68 proteins associated with the PLM index after correction for multiple testing (ie, base model). Most significantly decreased proteins were iron-related and included Hepcidin (LEAP-1), Ferritin, and Ferritin light chain. Most significantly increased proteins included RANTES, Cathepsin A, and SULT 1A3. Of 68 proteins significant in the base model, 17 were present in the 1300 panel, and 15 of 17 were replicated. The most significant proteins in the combined model were Hepcidin (LEAP-1), Cathepsin A, Ferritin, and RANTES. Exploration of proteins in RLS versus non-RLS identified Cathepsin Z, Heme oxygenase 2 (HO-2), Interleukin-17A (upregulated in the combined cohort), and Megalin (upregulated in STAGES only) although results were less significant than for proteins associated with PLM index. CONCLUSIONS: These results confirm the association of PLM with low iron status and suggest the involvement of catabolic enzymes in PLM/RLS.

Once-nightly sodium oxybate (FT218) improved symptoms of disrupted nighttime sleep in people with narcolepsy: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a plain language summary of a published article in the journal CNS Drugs. Narcolepsy is a rare sleep condition. Most people with narcolepsy experience disrupted nighttime sleep and have poor quality of sleep. Sometimes these symptoms are not easily diagnosed as a symptom of narcolepsy. Sodium oxybate is an approved treatment for narcolepsy. The only version of sodium oxybate that was available until 2023 required people to take their sodium oxybate at bedtime and then again in the middle of the night. The US Food and Drug Administration (FDA for short) has approved a once-nightly bedtime dose of sodium oxybate (ON-SXB for short, also known as FT218 or LUMRYZ™) to treat symptoms of narcolepsy in adults. These symptoms are daytime sleepiness and cataplexy, which is an episode of sudden muscle weakness. The once-nightly bedtime dose of ON-SXB removes the need for a middle-of-the-night dose of sodium oxybate. The REST-ON clinical study compared ON-SXB to a placebo (a substance that contains no medicine) to determine if it was better at treating symptoms of disrupted nighttime sleep associated with narcolepsy. This summary looks at whether; ON-SXB was better than placebo at treating symptoms of disrupted nighttime sleep. WHAT WERE THE RESULTS?: Compared to people who took placebo, people who took ON-SXB had fewer number of changes from deeper to lighter sleep stages and woke up less during the night. They also reported that they slept better at night and felt more refreshed when waking up in the morning. People with narcolepsy sometimes take alerting agents to help with sleepiness during the day, but alerting agents can cause difficulty sleeping at night. This study showed that people who took ON-SXB had better nighttime sleep even if they were taking alerting agents during the day. The most common side effects of ON-SXB included dizziness, nausea (feeling sick to your stomach), vomiting, headache, and bedwetting. WHAT DO THE RESULTS MEAN?: A once-nightly bedtime dose of ON-SXB is a narcolepsy treatment option for people without the need for a middle-of-the-night dose of sodium oxybate.

Accuracy of 11 Wearable, Nearable, and Airable Consumer Sleep Trackers: Prospective Multicenter Validation Study.

BACKGROUND: Consumer sleep trackers (CSTs) have gained significant popularity because they enable individuals to conveniently monitor and analyze their sleep. However, limited studies have comprehensively validated the performance of widely used CSTs. Our study therefore investigated popular CSTs based on various biosignals and algorithms by assessing the agreement with polysomnography. OBJECTIVE: This study aimed to validate the accuracy of various types of CSTs through a comparison with in-lab polysomnography. Additionally, by including widely used CSTs and conducting a multicenter study with a large sample size, this study seeks to provide comprehensive insights into the performance and applicability of these CSTs for sleep monitoring in a hospital environment. METHODS: The study analyzed 11 commercially available CSTs, including 5 wearables (Google Pixel Watch, Galaxy Watch 5, Fitbit Sense 2, Apple Watch 8, and Oura Ring 3), 3 nearables (Withings Sleep Tracking Mat, Google Nest Hub 2, and Amazon Halo Rise), and 3 airables (SleepRoutine, SleepScore, and Pillow). The 11 CSTs were divided into 2 groups, ensuring maximum inclusion while avoiding interference between the CSTs within each group. Each group (comprising 8 CSTs) was also compared via polysomnography. RESULTS: The study enrolled 75 participants from a tertiary hospital and a primary sleep-specialized clinic in Korea. Across the 2 centers, we collected a total of 3890 hours of sleep sessions based on 11 CSTs, along with 543 hours of polysomnography recordings. Each CST sleep recording covered an average of 353 hours. We analyzed a total of 349,114 epochs from the 11 CSTs compared with polysomnography, where epoch-by-epoch agreement in sleep stage classification showed substantial performance variation. More specifically, the highest macro F1 score was 0.69, while the lowest macro F1 score was 0.26. Various sleep trackers exhibited diverse performances across sleep stages, with SleepRoutine excelling in the wake and rapid eye movement stages, and wearables like Google Pixel Watch and Fitbit Sense 2 showing superiority in the deep stage. There was a distinct trend in sleep measure estimation according to the type of device. Wearables showed high proportional bias in sleep efficiency, while nearables exhibited high proportional bias in sleep latency. Subgroup analyses of sleep trackers revealed variations in macro F1 scores based on factors, such as BMI, sleep efficiency, and apnea-hypopnea index, while the differences between male and female subgroups were minimal. CONCLUSIONS: Our study showed that among the 11 CSTs examined, specific CSTs showed substantial agreement with polysomnography, indicating their potential application in sleep monitoring, while other CSTs were partially consistent with polysomnography. This study offers insights into the strengths of CSTs within the 3 different classes for individuals interested in wellness who wish to understand and proactively manage their own sleep.

Reply to Singh, G.D. Comment on "Dao et al. Retrospective Analysis of Real-World Data for the Treatment of Obstructive Sleep Apnea with Slow Maxillary Expansion Using a Unique Expansion Dental Appliance (DNA). Pathophysiology 2023, 30, 199-208".

In response to the commentary "Response to 'Retrospective analysis of real-world data for the treatment of obstructive sleep apnea with slow maxillary expansion'" [...].

An approach for determining the reliability of manual and digital scoring of sleep stages.

STUDY OBJECTIVES: Inter-scorer variability in sleep staging is largely due to equivocal epochs that contain features of more than one stage. We propose an approach that recognizes the existence of equivocal epochs and evaluates scorers accordingly. METHODS: Epoch-by-epoch staging was performed on 70 polysomnograms by six qualified technologists and by a digital system (Michele Sleep Scoring [MSS]). Probability that epochs assigned the same stage by only two of the six technologists (minority score) resulted from random occurrence of two errors was calculated and found to be <5%, thereby indicating that the stage assigned is an acceptable variant for the epoch. Acceptable stages were identified in each epoch as stages assigned by at least two technologists. Percent agreement between each technologist and the other five technologists, acting as judges, was determined. Agreement was considered to exist if the stage assigned by the tested scorer was one of the acceptable stages for the epoch. Stage assigned by MSS was likewise considered in agreement if included in the acceptable stages made by the technologists. RESULTS: Agreement of technologists tested against five qualified judges increased from 80.8% (range 70.5%-86.4% among technologists) when using the majority rule, to 96.1 (89.8%-98.5%) by the proposed approach. Agreement between unedited MSS and same judges was 90.0% and increased to 92.1% after brief editing. CONCLUSIONS: Accounting for equivocal epochs provides a more accurate estimate of a scorer's (human or digital) competence in scoring sleep stages and reduces inter-scorer disagreements. The proposed approach can be implemented in sleep-scoring training and accreditation programs.

Partial endorsement of: "Video-polysomnography procedures for diagnosis of rapid eye movement sleep behavior disorder (RBD) and the identification of its prodromal stages: Guidelines from the International RBD Study Group" by the World Sleep Society.

Updated guidelines for the video-polysomnography (vPSG) procedures for diagnosing rapid eye movement sleep behavior disorder (RBD) and the identification of its prodromal stages have recently been proposed by the Neurophysiology Working Group of the International RBD Study Group (IRBDSG). These guidelines were selected for review by a World Sleep Society (WSS) Parasomnias Task Force and the WSS International Sleep Medicine Guidelines Committee. A survey was completed by sleep society leaders and prominent sleep clinicians and researchers in 31 WSS member countries across six continents, focused on sleep technologist training and certification; extent of public/private health insurance coverage for the vPSG evaluation of RBD; extent of hospital-based sleep-technologist-attended overnight vPSG studies; availability of video during PSG studies; and sufficient specification of PSG machines to record and analyze REM sleep without atonia. The findings from this survey indicated that most health systems and medical communities across WSS member countries would not be capable of implementing the proposed more stringent guidelines, which would then strongly interfere with the diagnosis of RBD in a large portion of patients who would not be able to receive the required (often repeated) vPSG evaluation. Therefore, the WSS can only partially endorse the updated guidelines and concludes that the current International Classification of Sleep Disorders-3rd edition diagnostic criteria for RBD should still be retained as the standard reference for the diagnosis of RBD, and that further discussion across all members of the IRBDSG should take place to ensure the feasibility of any future proposed changes.

Prediction of Sleep Stages Via Deep Learning Using Smartphone Audio Recordings in Home Environments: Model Development and Validation.

BACKGROUND: The growing public interest and awareness regarding the significance of sleep is driving the demand for sleep monitoring at home. In addition to various commercially available wearable and nearable devices, sound-based sleep staging via deep learning is emerging as a decent alternative for their convenience and potential accuracy. However, sound-based sleep staging has only been studied using in-laboratory sound data. In real-world sleep environments (homes), there is abundant background noise, in contrast to quiet, controlled environments such as laboratories. The use of sound-based sleep staging at homes has not been investigated while it is essential for practical use on a daily basis. Challenges are the lack of and the expected huge expense of acquiring a sufficient size of home data annotated with sleep stages to train a large-scale neural network. OBJECTIVE: This study aims to develop and validate a deep learning method to perform sound-based sleep staging using audio recordings achieved from various uncontrolled home environments. METHODS: To overcome the limitation of lacking home data with known sleep stages, we adopted advanced training techniques and combined home data with hospital data. The training of the model consisted of 3 components: (1) the original supervised learning using 812 pairs of hospital polysomnography (PSG) and audio recordings, and the 2 newly adopted components; (2) transfer learning from hospital to home sounds by adding 829 smartphone audio recordings at home; and (3) consistency training using augmented hospital sound data. Augmented data were created by adding 8255 home noise data to hospital audio recordings. Besides, an independent test set was built by collecting 45 pairs of overnight PSG and smartphone audio recording at homes to examine the performance of the trained model. RESULTS: The accuracy of the model was 76.2% (63.4% for wake, 64.9% for rapid-eye movement [REM], and 83.6% for non-REM) for our test set. The macro F1-score and mean per-class sensitivity were 0.714 and 0.706, respectively. The performance was robust across demographic groups such as age, gender, BMI, or sleep apnea severity (accuracy 73.4%-79.4%). In the ablation study, we evaluated the contribution of each component. While the supervised learning alone achieved accuracy of 69.2% on home sound data, adding consistency training to the supervised learning helped increase the accuracy to a larger degree (+4.3%) than adding transfer learning (+0.1%). The best performance was shown when both transfer learning and consistency training were adopted (+7.0%). CONCLUSIONS: This study shows that sound-based sleep staging is feasible for home use. By adopting 2 advanced techniques (transfer learning and consistency training) the deep learning model robustly predicts sleep stages using sounds recorded at various uncontrolled home environments, without using any special equipment but smartphones only.

Association of Backscattered Ultrasonographic Imaging of the Tongue With Severity of Obstructive Sleep Apnea in Adults.

Importance: Determining interventions to manage obstructive sleep apnea (OSA) depends on clinical examination, polysomnography (PSG) results, and imaging analysis. There remains the need of a noninvasive and cost-effective way to correlate relevant upper airway anatomy with severity of OSA to direct treatment and optimize outcome. Objective: To determine whether backscattered ultrasonographic imaging (BUI) analysis of the tongue is associated with severity of OSA in adults. Design, Setting, and Participants: In this prospective, single-center, diagnostic study of a consecutive series of patients (aged ≥18 years) at a sleep surgery clinic, the 89 included patients had a PSG within 3 years at the time of ultrasonography and BUI analysis between July 2020 and March 2022. Patients were excluded if body mass index had changed more than 10% since time of PSG. A standardized submental ultrasonographic scan with laser alignment was used with B-mode and BUI analysis applied to the tongue. The B-mode and BUI intensity were associated with the apnea-hypopnea index (AHI), a measure of severity of apnea from normal (no OSA) to severe OSA. Exposures: Ultrasonography and PSG. Main Outcomes and Measures: The main outcomes were BUI parameters and their association with AHI value. Results: Eighty-nine patients were included between July 2020 and March 2022. A total of 70 (78.7%) male patients were included; and distribution by race and ethnicity was 46 (52%) White participants, 22 (25%) Asian participants, and 2 (2%) African American participants, and 19 (21%) others. Median (IQR) age was 37.0 (29.0-48.3) years; median (IQR) BMI was 25.3 (23.2-29.8); and median (IQR) AHI was 11.1 (5.6-23.1) events per hour. At the middle to posterior tongue region, the 4 OSA severity levels explained a significant portion of the BUI variance (η2 = 0.153-0.236), and a significant difference in BUI values was found between the subgroups with AHI values of less than 15 (no OSA and mild OSA) and greater than or equal to 15 (moderate OSA and severe OSA) events per hour. The echo intensity showed no significant differences. The BUI values showed a positive association with AHI, with a Spearman correlation coefficient of up to 0.43. Higher BUI values remained associated with higher AHI after correction for the covariates of BMI and age. Conclusions and Relevance: In this prospective diagnostic study, standardized BUI analysis of the tongue was associated with OSA severity. With the practicality of ultrasonography, this analysis is pivotal in connecting anatomy with physiology in treatment planning for patients with OSA.

Evaluation of consensus sleep stage scoring of dysregulated sleep in Parkinson's disease.

OBJECTIVE: Sleep dysregulation in Parkinson's disease (PD) has been hypothesized to occur, in part, from dysfunction in the basal ganglia-cortical circuit. Assessment of this relationship requires accurate sleep stage determination, a known challenge in this clinical population. Our objective was to optimize the consensus on the sleep staging process and reduce interrater variability in a cohort of advanced PD subjects. METHODS: Fifteen PD subjects were enrolled from three sites in a clinical trial that involved recordings from subthalamic nucleus (STN) deep brain stimulation (DBS) leads (NCT04620551). Video polysomnography (vPSG) data for a total of 45 nights were analyzed. Four experienced scorers independently scored data on initial review. Epochs with less than 75% consensus were flagged for secondary review. In secondary review of discordant epochs, two of the original scorers re-assessed epochs, from which the final consensus stage was derived. RESULTS: Sleep stage classification agreement averaged 83.10% across all sleep stages on initial scoring (IS), and on secondary consensus scoring (CS) review, agreement reached 96.58%. Greatest disagreement was noted in determination of awake epochs (33.6% of discordant epochs) and non-rapid-eye-movement stage 2 (N2) epochs (31.8% of discordant epochs). Scoring discrepancy was resolved with direct measurement of cortical frequency and amplitudes, physiologic context of the epoch, and video review. CONCLUSION: Our method of multi-level initial and then secondary consensus review scoring resulted in consensus scoring agreement superior to conventional standards. This work features a custom-engineered vPSG software and review platform for integration of consensus sleep stage scoring in a multi-site clinical trial.

Clinician Preferences for Oxybate Treatment for Narcolepsy: Survey and Discrete Choice Experiment.

INTRODUCTION: Immediate-release sodium oxybate (SXB) has been Food and Drug Administration (FDA)-approved to treat narcolepsy since 2002; in 2020, a mixed-salt oxybates formulation was also approved. Both are taken at bedtime with a second dose taken 2.5-4 h later. A third oxybate option, an investigational extended-release SXB, may soon be available. This study was undertaken to understand clinicians' preferences between these 3 different oxybate treatments. METHODS: Clinicians in active clinical practice for 3-35 years and experience treating patients with narcolepsy were recruited. A 30-min web-based survey quantified narcolepsy disease-state attitudes, treatment perceptions, and satisfaction with oxybates on 9-point scales. A discrete choice experiment (DCE) of 12 choice sets, with 2 hypothetical treatment profiles in each, was used to capture clinician preferences about overall oxybate therapy preference, impact on patient quality of life (QoL), and patient anxiety/stress. Attributes associated with current therapies and those expected to be available in the near future were included in the design. RESULTS: The clinicians surveyed (n = 100) indicated that narcolepsy has a negative impact on patient QoL (mean rating, 7.7) and rated impact on QoL and treatment efficacy as the most important aspects of a narcolepsy treatment (mean rating, 7.3-7.7). Clinicians with experience prescribing oxybates had moderately high satisfaction with SXB and mixed-salt oxybates efficacy (mean ratings, 6.5-6.9) and safety (mean ratings, 6.1-6.7) and lower satisfaction with nightly dosing frequency (mean rating, 5.9 and 6.3, respectively). In the DCE, dosing frequency was the most important attribute driving overall product choice, patient QoL, and reducing patient anxiety/stress (relative attribute importance, 46.1, 41.7, and 44.0, respectively), with once nightly preferred over twice nightly. CONCLUSION: Clinicians indicated a significantly higher preference for the once-at-bedtime dosing schedule versus twice nightly in selecting oxybate therapies overall and when aiming to improve patient QoL or reduce patient anxiety.

Current medications for narcolepsy include immediate-release sodium oxybate and mixed-salt oxybates. People taking these oxybates for narcolepsy take 1 dose at bedtime and must wake up 2.5­4 h later for the second dose. An investigational sodium oxybate, designed as a single bedtime dose, has been tentatively approved by the US Food and Drug Administration. This study used a 30-min web-based survey to learn what clinicians think about narcolepsy and narcolepsy medicines. A discrete choice experiment was used to identify which properties of current/future oxybate medicines are most important in a narcolepsy treatment. In this exercise, relevant properties of current/future oxybate medicines were mixed and matched to create hypothetical medicine profiles. Clinicians selected from these profiles which medication they preferred overall, which would improve patient quality of life, and which would reduce patient anxiety when thinking about taking the treatment. Clinicians were moderately satisfied with the effectiveness and safety of current narcolepsy medications. They strongly preferred oxybate treatments with fewer nightly doses and agreed that waking up for the second oxybate dose causes stress for patients. In the discrete choice experiment, the number of doses each night was the product characteristic that had the biggest impact on clinicians picking a medicine for narcolepsy. This was true for overall medicine choice, choosing a medicine that would improve patient quality of life, and choosing one that would reduce patient anxiety/stress. If granted marketing approval, extended-release sodium oxybate will be a once-at-bedtime option that may overcome challenges with current oxybate therapies.

Retrospective Analysis of Real-World Data for the Treatment of Obstructive Sleep Apnea with Slow Maxillary Expansion Using a Unique Expansion Dental Appliance (DNA).

In addition to mandibular advancement devices, dental expansion appliances are an important clinical approach for achieving an increased intra-oral space that promotes airflow and lessens the frequency or severity of apneic events in patients diagnosed with obstructive sleep apnea (OSA). It has been thought that dental expansion in adults must be preceded by oral surgery; however, in this paper, we examine the results of a new technique for slow maxillary expansion without any surgical procedures. The palatal expansion device, DNA (Daytime-Nighttime Appliance), was reviewed in this retrospective study, particularly regarding its effects on measurements of transpalatal width, airway volume, and apnea-hypopnea indices (AHI) as well as its common modalities and complications. The DNA effectively reduced AHI by 46% (p = 0.00001) and significantly increased both airway volume and transpalatal width (p < 0.00001). After DNA treatment, 80% of patients showed some improvement in AHI scores with 28% of patients having their OSA symptoms completely resolved. Compared to the use of mandibular appliances, this approach is intended to create a sustained improvement in airway management that can reduce or eliminate dependence on continuous positive airway pressure (CPAP) or other OSA treatment devices.

Nicotine, alcohol, and caffeine use among individuals with untreated obstructive sleep apnea.

BACKGROUND: Psychoactive substance use (i.e., nicotine, alcohol, and caffeine) has substantial effects on sleep architecture in healthy individuals, but their effects in those with obstructive sleep apnea (OSA) have not been well described. We aimed to describe the association between psychoactive substance use and sleep characteristics and daytime symptoms in individuals with untreated OSA. METHODS: We performed a secondary, cross-sectional analysis of The Apnea Positive Pressure Long-term Efficacy Study (APPLES). Exposures included current smoking, alcohol and caffeine use in individuals with untreated OSA. Outcome domains included subjective and objective sleep characteristics, daytime symptoms, and comorbid conditions. Linear or logistic regression assessed the association between substance use and each domain (e.g., self-reported sleep duration, total polysomnographic sleep time, sleepiness, and anxiety). RESULTS: Of the 919 individuals with untreated OSA, 116 (12.6%) were current cigarette smokers, 585 (63.7%) were moderate or heavy alcohol users, and 769 (83.7%) were moderate or heavy caffeine users. Participants were on average 52.2±11.9 years old, 65.2% were male with a median BMI of 30.6 (IQR: 27.2, 35.9, kg/m2). Current smokers exhibited lower sleep duration (0.3 h), longer sleep latency (5 min) compared with non-smokers (all p-values < 0.05). People with heavy or moderate alcohol use exhibited more REM sleep (2.5 and 5% of total sleep time respectively), as did those with moderate caffeine use (2%, p-values < 0.05). The combined smoker plus caffeine group exhibited shorter sleep duration (0.4 h, p-value < 0.05) and higher risk for chronic pain [Odds Ratio (95%CI) = 4.83 (1.57, 14.9) compared with non-users. CONCLUSIONS: Psychoactive substance use is associated with sleep characteristics and clinically relevant correlates in people with untreated OSA. Further investigation into the effects that various substances have on this population may present opportunities to understand disease mechanisms more fully and increase the effectiveness of treatment in OSA.

Sodium oxybate in treatment-resistant rapid-eye-movement sleep behavior disorder.

STUDY OBJECTIVES: Symptomatic therapies for rapid-eye-movement (REM) sleep behavior disorder (RBD) are limited. Sodium oxybate (SXB), a gamma-aminobutyric acid (GABA)-B agonist, could be effective but has not been evaluated against placebo. METHODS: This double-blind, parallel-group, randomized, placebo-controlled trial in 24 participants was conducted at the Stanford Sleep Center. Patients were adults with definite iRBD or Parkinson's disease and probable RBD (PD-RBD), and persistence of ≥ 2 weekly episodes despite standard therapy. Patients were randomized 1:1 to receive SXB during a 4-week titration followed by a 4-week stable dosing period. Primary outcome was number of monthly RBD episodes according to a diary filled by patients and partners. Secondary outcomes were severity, number of severe RBD episodes, and objective RBD activity on video polysomnography. RESULTS: Twelve iRBD and 12 PD-RBD participated (mean 65.8 years), and 22 (n = 10 SXB, 12 placebo) completed the study. Although no significant between-group difference was found, SXB showed reduction of monthly RBD episodes by 23.1 (95% CI -36.0, -10.2; p = 0.001) versus 10.5 with placebo (95% CI, -22.6, 1.6; p = 0.087). Improvement from baseline was similarly observed for RBD overall severity burden (each episode weighted for severity), number of severe episodes, and objective RBD activity per video-polysomnography. Two participants receiving SXB withdrew due to anxiety and dizziness. The majority of adverse events are otherwise resolved with dose adjustment. CONCLUSION: SXB could reduce RBD symptoms; however, response was inconsistent and a large placebo effect was observed across patient-reported outcomes. Larger studies using objective endpoints are needed. CLINICAL TRIAL: Treatment of REM Sleep Behavior Disorder (RBD) With Sodium Oxybate https://clinicaltrials.gov/ct2/show/NCT04006925 ClinicalTrials.gov identifier: NCT04006925.

A roadmap of craniofacial growth modification for children with sleep-disordered breathing: a multidisciplinary proposal.

Craniofacial modification by orthodontic techniques is increasingly incorporated into the multidisciplinary management of sleep-disordered breathing in children and adolescents. With increasing application of orthodontics to this clinical population it is important for healthcare providers, families, and patients to understand the wide range of available treatments. Orthodontists can guide craniofacial growth depending on age; therefore, it is important to work with other providers for a team-based approach to sleep-disordered breathing. From infancy to adulthood the dentition and craniofacial complex change with growth patterns that can be intercepted and targeted at critical time points. This article proposes a clinical guideline for application of multidisciplinary care with emphasis on dentofacial interventions that target variable growth patterns. We also highlight how these guidelines serve as a roadmap for the key questions that will influence future research directions. Ultimately the appropriate application of these orthodontic techniques will not only provide an important therapeutic option for children and adolescents with symptomatic sleep-disordered breathing but may help also mitigate or prevent its onset.