bluuebunny/crossref_metadata_2025_split huggingface dataset:
0698 A Comparison Of Two Visual Hypopnea Classification Methods
Authors: Dupuy-McCauley K , Mudrakola H V , Morgenthaler T I 
Published: May 2020

Abstract

Introduction
The rules for classifying apneas as either obstructive or central using usual polysomnography (PSG) channels are well established, but classification of hypopneas is less straightforward without special sensors. Visual scoring methods have been proposed by the American Academy of Sleep Medicine (AASM) and by Randerath, et al. These two scoring methods have never been compared. We evaluated these two scoring methods for clinical use.

Methods
We selected 50 hypopnea segments from patient’s PSGs with very clear obstructive physiology (average total AHI 48.6, central AI 0), assumed to be obstructive hypopneas, and from patient’s PSGs with very clear central physiologies (average total AHI 34.3, obstructive AI 0.3), assumed to be central hypopneas. These 100 hypopnea-containing PSG segments (HCPS) were deidentified, placed in randomized order, and sent to two groups of 6 PSG scorers (2 RPSGTs, 2 sleep medicine fellows, 2 sleep medicine specialists). One group scored using the AASM criteria and the other used the Randerath algorithm. After a washout period, re-randomized HCPS were sent to be scored using the alternative method. We used Fleiss’ kappa to determine inter-rater reliability—i.e., how consistently multiple scorers came to the same conclusion about a given hypopnea segment using each method, and accuracy—how often the scorers rated the HCPS in a manner consistent with the assumed physiology. We also recorded the time it took to score.

Results
Overall accuracy of both methods was 68%. Among 12 scorers, Fleiss’ Kappa coefficient was 0.32 and 0.27 for the AASM and Randerath scoring methods, respectively. Average scoring time (24.3 minutes for AASM and 26.2 minutes for Randerath) was similar (p=0.79).

Conclusion
Inter-rater agreement was only fair using these methods, and accuracy was only 68%. More work is needed to discover a convenient, non-invasive way to reproducibly and accurately characterize hypopneas.

Support
This project does not have any funding support.
0706 Comparing the Dose-Response Curves of Upper Airway Stimulation and CPAP Usage on Changes in Epworth Sleepiness Scale
Authors: Kazaglis L , Hsia J , Green K , Iber C 
Published: May 2020

Abstract

Introduction
Upper Airway Stimulation (UAS) and Continuous Positive Airway Pressure (CPAP) are trackable therapies for obstructive sleep apnea. We used recent big-data cohorts to compare changes in sleepiness versus usage.

Methods
ADHERE is an international registry of real-world UAS outcomes from 2016 to date. General UAS criteria are CPAP intolerance, AHI 15-65 (&lt;25% central+mixed), and suggested BMI≤35. Baseline ESS is collected from the medical record, and follow-up ESS and usage is collected 2-4 months after therapy activation. M Health Fairview maintains a database of cross-linked CPAP and EHR data. All new adult sleep patients from 2015 onward were included paralleling ADHERE: BMI≤35, AHI 15-65, and daily CPAP-EHR data starting at least 60 days prior to 2nd ESS measurement. Baseline ESS was collected at consult, and follow-up ESS was collected approximately 6 months later. Device-reported usage hours were compared with the changes in ESS from baseline.

Results
UAS (n=690) and CPAP (n=514) groups were similar: age 59.7±10.8 versus 59.7±13.6, 78% versus 75% male, and AHI 35.3±14.4 versus 33.8±14.0. UAS group was slightly less obese, BMI 29.3±3.9 versus 30.0±3.4 (p=0.001), with higher baseline ESS, 11.4±5.6 versus 8.6±5.3 (p&lt;0.001). UAS usage was higher at 6.4±2.0 hours/night versus 5.2±2.0 hours/night with CPAP (p&lt;0.001). UAS group average ESS decreased 2.5 points for patients with 0-4 hours of use (n=81), decreasing to 3.8 points with at 4 or more hours of use (n=609). CPAP group average ESS decreased 2.5 points for patients with 0-4 hours of use (n=125), decreasing to 3.3 points with at 4 or more hours of use (n=389).

Conclusion
Compared to prior works and the UAS cohort, this CPAP cohort was more likely to have normal ESS at baseline. UAS and CPAP both demonstrate a dose-response curve associating increasing hourly usage with larger ESS reductions.

Support
Kent Lee of Inspire Medical Systems provided background information and access to a de-identified ADHERE data set for analysis.
0708 A Study To Determine Efficacy Of A Device In Anticipating Obstructive Sleep Apnea Events
Authors: Rechul D , Rechul K 
Published: May 2020

Abstract

Introduction
Current treatment options for obstructive sleep apnea pose multiple challenges ranging from issues with therapy adherence (i.e. PAP) to partial effectiveness (i.e. MAD) or invasiveness (i.e. implantable nerve stimulation devices). SleepMethods, Inc. designed a device that proposed to solve these issues. It consisted of two integrated mechanisms; one to anticipate the development of an obstructive event and the other to deliver therapeutic intervention to abort the process of airway collapse before it ensued. A clinical trial was conducted to test the efficacy of the system designed to anticipate obstructive sleep apnea events.

Methods
Ten adults (7M;3F) aged 18-80y/o (avg. 54.7y/o) with a known AHI ≥ 15/hr (avg. AHI = 42.6/hr) underwent 1 overnight PSG recording while wearing the device. Patients were required to forego their usual CPAP therapy on the night of study in efforts to expose the device to an adequate number of total obstructive events (defined as apneas and hypopneas; RERAs and snores were excluded). Standard PSG analysis was performed. Scoring rules were applied to determine whether signals were true/false positives and/or true/false negatives based on pre-clinical data showing anticipation accuracy for up to 45 seconds prior to an obstructive airway event.

Results
Preliminary results suggest the device functions with 96.9% sensitivity and about 67.1% PPV. Data analysis is ongoing to determine specificity, statistical significance, etc.

Conclusion
The device has shown promise in pre-clinical and clinical trials to accurately and consistently anticipate airway collapse; a possible breakthrough in designing more targeted therapies aimed at aborting obstructive sleep apnea events before they ensue to a clinically significant degree.

Support
N/A
0714 Effect of One-Week Velopharyngeal-Task Training on Genioglossus Corticomotor Excitability and Sleep Apnea Severity
Authors: Li W , Wei Z , Wang W , Frédéric S 
Published: May 2020

Abstract

Introduction
The effectiveness of the contraction of the UA dilator muscles plays a crucial role in the maintenance of UA patency. This study aimed to assess the effects of one-week velopharyngeal-task training (VTT) on sleep apnea severity and its genioglossus (GG) corticomotor excitability.

Methods
Ten patients with sleep apnea underwent 1 h VTT on seven consecutive days. During the VTT protocol, subjects were asked to develop repetitive intra-oral positive pressure using cheek-bulging maneuvers while wearing a mouth piece to keep the jaw opened and maintaining an exclusive nasal breathing. They were encouraged to generate approximately 4% of Max pressure by maintaining the pressure inside the corresponding pre-set pressure target window for 2 sec every 10 sec. PSG recording and GG transcranial magnetic stimulation (TMS) response was obtained before and after the one-week VTT.

Results
One-week VTT was associated with a global AHI decrease by 33.8% (pre-VTT: 34.5±31.9 n/h; post-VTT: 25.5±26.7 n/h; p&lt; 0.05) and progressed from moderate/severe to mild/moderate in 40% of patients. Although the bulging pressure remained unchanged (pre-VTT: 17.1±5.6 kPa, post-VTT: 19.4±5.4 kPa, p&gt; 0.05), the amplitude of GG motor evoked potential in response to TMS significantly increased after the one-week VTT (pre-VTT: 639.4±380.9mV; post-VTT: 1128.5±623.9mV; p&lt; 0.05).

Conclusion
One-week VTT is sufficient to confer clinical benefits on patients with sleep apnea. VTT protocol is not oriented toward strength gain, but rather toward an enhancement in the upper airway muscle cortical excitability and improvement in the coordination of their contraction. The authors consider these results to be potentially clinically relevant and worthy of further investigation in a large randomized trial.

Support
National Natural Science Foundation of China, Grant/Award Number: 81670085.
0723 Associations Between Opioids, Non-Opioids and Central Sleep Apnea: A Case-Control Study
Authors: Gavidia R , Meng A L , Emenike A , Hershner S , Jansen E , Goldstein C , Dunietz G L 
Published: May 2020

Abstract

Introduction
Opioids are known to contribute to central sleep apnea (CSA), as they depress responsiveness to carbon dioxide and hypoxia. However, the role of non-opioid medications (antihistamines, myorelaxants, neuroleptics, antidepressants, and hypnotics) in CSA remains unclear. Given the hypothesized impact of non-opioids on the central nervous system, we examined associations between opioid and non-opioid medications and CSA.

Methods
Among all adults who underwent polysomnography testing at the University of Michigan’s Sleep Center between 2013-2018 (n=10,479), we identified 105 cases of CSA. Of these patients, we randomly selected 300 controls. Demographic and health characteristics, use of medications were obtained from medical charts. We classified study participants into three categories based on medication use: non-opioids only, opioids alone or in combination with non-opioids, and none. CSA was defined as a binary outcome using polysomnographic criteria as per the International Classification of Sleep Disorders-Third Edition. We used logistic regression to examine associations between medication use and CSA.

Results
Among participants, male:female ratio was 1:1 with a mean age of 49 (±14.3 SD) years. Opioid use alone was rare (4%), but more common in combination with non-opioids (17%), while the exclusive use of non-opioids was found among 38%.
In adjusted analyses for age and sex, those who used non-opioid alone were less likely to have a CSA diagnosis (OR=0.88, (95% CI 0.5-1.6); however, the use of opioids (alone or in combination with non-opioids) was associated with a 4-fold higher odds of CSA.

Conclusion
These data suggest that non-opioids have a protective influence on CSA. Conversely, opioids, alone, or in combination with non-opioids, were associated with increased CSA risk, that may be attributed to opioids alone, or to opioids and non-opioids interactions. However, as opioids were mostly co-prescribed with non-opioids, the sole effect of opioids from the synergistic effect with non-opioids are difficult to disentangle.

Support
Dr. Gavidia was supported by a T32 Post-Doctoral Fellowship in Neuroscience NIH/NINDS T32 NS 007222
0724 Altered Brain Network Organization in Patients With Obstructive Sleep Apnea
Authors: Park H , Cha J , Kim H , Joo E 
Published: May 2020

Abstract

Introduction
Previous functional MRI (fMRI) studies have reported altered brain networks in patients with obstructive sleep apnea (OSA), but the extent of such abnormal connectivity was inconsistent across studies. Moreover, despite the important role of the cerebellum in respiration and OSA, connections of the cerebellum to the cerebral cortex have been rarely assessed. Here, we investigated functional network changes in cerebral and cerebellar cortices of OSA patients.

Methods
Resting-state fMRI, polysomnography and neuropsychological (NP) tests data were acquired from 74 treatment naïve OSA patients (age: 45.8±10.7 years, apnea-hypopnea index: 46.4±18.5 /h) and 33 normal controls (39.6±9.3 years). Connectivity matrices were extracted by computing correlation coefficients from various ROIs, and Fisher r-to-z transformations. ROIs consisted of 234 regions matched to 17 functional networks, including 200 parcels of the cortex, and 34 parcels of the cerebellum. Between-group connectivity with age as a covariate was analyzed, and threshold for FDR correction was set at q&lt;0.05. In the functional connections that showed the significant group differences, linear regression was conducted to examine the association between connectivity and composite score of NP tests in OSA patients.

Results
OSA subjects showed decreased attention, executive function, verbal fluency and verbal memory compared to controls. Resting-state functional connectivity was increased between regions involved in the default mode network (DMN), including left medial prefrontal, ventrolateral prefrontal and lateral temporal cortices. In OSA, the connectivity changes between these DMN areas negatively correlated with attention/executive function and verbal fluency. Multiple cerebellar regions showed reduces in connectivity with cerebral cortical areas including frontal eye field, temporoparietal junction, temporo-occipital gyrus, and parieto-occipital association cortex.

Conclusion
OSA affects mainly the DMN and cerebello-cerebral pathway. The disruption of function in these two networks are known to relate to sleep deprivation and respiratory abnormality. The abnormal DMN found in OSA patients further related to their cognitive impairment.

Support
This research was supported by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning, Republic of Korea (2017R1A2B4003120) and by Samsung Biomedical Research Institute grant (OTC1190671)
0730 Individuals Receiving Methadone For Medication-Assisted Treatment Of Opioid Use Disorder Show Evidence Of Respiratory Depression
Authors: Finlay M , Wilson M , Erwin J A , Hansen D A , Layton M E , Quock R M , Van Dongen H 
Published: May 2020

Abstract

Introduction
A well-established consequence of opiate use is respiratory depression during sleep, with a high prevalence of central sleep apneas. Medication-assisted treatment (MAT) is a widely used therapy for opioid use disorder (OUD) designed to reduce withdrawal symptoms and drug cravings. We investigated the presence of respiratory depression during sleep in patients receiving methadone-based opioid replacement treatment as part of a MAT program for OUD.

Methods
N=6 individuals (5 females, ages 43.8±12.8y, BMI 27.2±4.1kg/m2), who were within 90 days of methadone initiation, underwent in-laboratory overnight polysomnography (8h TIB, 22:00-06:00). Apneaic and hypopneic events were determined using AASM criteria.

Results
The average Apnea-Hypopnea Index (AHI) was 16.5±9.0 events/h, with 2 individuals exceeding the threshold of moderate sleep apnea (&gt;15 events/h). 89.5% of the observed apnea-hypopnea events occurred during NREM sleep. Of all events, 57.1±16.3% were central apneas; and of all obstructive, central, and mixed apnea events, 93.0±14.3% were central apneas.

Conclusion
Individuals with OUD receiving methadone-based MAT may be at risk of respiratory depression during sleep, as evidenced by the frequent occurrence of central sleep apneas. Such risk could be a contributing factor in opioid overdose deaths. Currently, performing respiratory assessments during sleep is not considered standard of care in MAT programs. Our preliminary data suggest that monitoring and treatment of respiratory depression during sleep may be indicated in OUD patients on methadone-based MAT.

Support
Supported in part by a seed grant from the Washington State University Office of Research Advancement and Partnerships.
0732 Quantitative Characterization Of Sleep Disordered Breathing Dynamics
Authors: Chen S , Eden U , Prerau M 
Published: May 2020

Abstract

Introduction
Sleep-disordered breathing (SDB) is a dynamic process in which the rate of respiratory events is highly influenced by numerous covariates, such as sleep stage, body position dominance, time of night, and overall instability of sleep architecture. Additionally, respiratory event rate likely has history dependence, such that the likelihood of a respiratory event is influenced by the timing of previous events. Despite its dynamic nature, clinical diagnosis collapses the complex process of SDB to a single number measuring the average rate of respiratory event occurrence— the apnea-hypopnea index (AHI). Thus, potentially valuable information is being lost by ignoring SDB temporal dynamics and history dependence.

Methods
We apply a general point process framework to sleep apnea events to develop parametric models of a time-varying instantaneous apnea rate given clinical covariates (e.g. EEG power, sleep stage, body position). Develop models of apnea history dependence, describing the likelihood of events given past event times. In doing so, we are able to compute an “instantaneous AHI”, which measures the moment-by-moment event rate, which evolves temporally as a function of other clinical observations as well as event history. We apply our model to data from the MESA cohort (include number of subjects, male/female here). We then applied dimensionality-reduction methods to assess any population phenotypes.

Results
For every subject, we computed a time-varying AHI for each time point in their polysomnogram and estimated the influence of each of the measured covariates on the instantaneous rate. Results showed that the greatest predictor of apnea events were related to history dependence. Clustering analysis showed no distinct clusters, but rather a constant gradient of changes in history dependence.

Conclusion
These results suggest that the greatest predictor of an apnea event onset is the timing previous event. Moreover, the way in which previous events influence subsequent events can be used as a means of phenotyping, paving the way towards identifying optimal personalized treatment.

Support
National Institute of Neurological Disorders and Stroke Grant R01 NS-096177
0740 Quality of Life in Phase 3, Placebo-Controlled, Double-Blind, Randomized Withdrawal Study of JZP-258 in Adults with Narcolepsy with Cataplexy
Authors: Foldvary-Schaefer N , Thorpy M J , Dauvilliers Y , Roy A , Tang L , Skowronski R , Šonka K , Bogan R K 
Published: May 2020

Abstract

Introduction
Narcolepsy negatively impacts health-related quality of life (HRQoL). Sodium oxybate is a standard of care for the treatment of cataplexy and excessive daytime sleepiness in narcolepsy. JZP-258 is an oxybate product candidate with 92% less sodium. Efficacy and safety of JZP-258 were established in a double-blind randomized withdrawal study in adults with narcolepsy with cataplexy.

Methods
Participants 18-70 years of age began JZP-258 treatment during a 12-week, open-label, optimized treatment and titration period, followed by a 2-week stable-dose period (SDP). Participants were then randomized to receive placebo or continue JZP-258 treatment during a 2-week, double-blind, randomized withdrawal period (DBRWP). HRQoL assessments included the 36-Item Short Form Health Survey Version 2 (SF-36) and 5-level EuroQoL 5-Dimensions Self-Report Questionnaire (EQ-5D-5L).

Results
201 participants enrolled; 134 were randomized and received at least 1 dose of double-blind study medication (efficacy population; placebo, n=65; JZP-258, n=69). Decreased scores (worsening) were observed in participants randomized to placebo compared with participants randomized to continue JZP-258 treatment for the SF-36 physical component summary (median [Q1, Q3], −1.92 [−3.46, 1.73] for placebo and −0.03 [−2.07, 2.41] for JZP-258; nominal P=0.02), SF-36 mental component summary (−1.92 [−6.28, 1.34] for placebo and 1.55 [−1.88, 3.78] for JZP-258; nominal P=0.03), and EQ-5D-5L visual analog scale (−5.00 [−10.0, 5.00] for placebo and 0 [0, 5.00] for JZP-258; nominal P=0.01). No change was observed in the EQ-5D-5L crosswalk index (0 [−0.05, 0.03] for placebo and 0 [−0.01, 0.03] for JZP-258; nominal P=0.39). The overall safety profile of JZP-258 was similar to sodium oxybate.

Conclusion
HRQoL worsened in those randomized to placebo during DBRWP but remained stable in participants who continued JZP-258 treatment.

Support
Jazz Pharmaceuticals
0743 The Pharmacokinetic Adverse Event Relationship for FT218, a Once-Nightly Sodium Oxybate Formulation
Authors: Seiden D , Grassot J , Monteith D , Dubow J 
Published: May 2020

Abstract

Introduction
Sodium oxybate is an effective treatment for excessive daytime sleepiness and cataplexy in patients with narcolepsy. The approved formulation requires twice-nightly dosing: at bedtime and 2.5 - 4 hours later, which results in two distinct Cmax’s. FT218 is a controlled-release formulation of sodium oxybate intended for once-nightly dosing, using Avadel’s proprietary Micropump™ technology. The objective of this study was to evaluate the pharmacokinetic-adverse event (AE) relationship for FT218, an investigational once-nightly sodium oxybate formulation.

Methods
Six single-dose, randomized, crossover studies that assessed the pharmacokinetics of FT218 at 4.5, 6, 7.5 and 9 g in healthy voluntters were used in this analysis. Lattice plots, “spaghetti” plots, and scatter plots of individual gamma hydroxybutyrate concentrations and indicators when AEs by system, organ, or class (SOC) were created to determine any PK-AE relationship.

Results
A total of 129 healthy volunteers received single doses of FT218 between 4.5 - 9 g. Most AEs, specifically for the neurological and gastrointestinal SOC, occurred close to Tmax, during the Cmax period, which for FT218 was around 1.5-2 hours after dosing. These AEs were known AEs associated with sodium oxbyate. There appeared to be no clear correlation between individual plasma GHB concentrations levels and AEs between subjects. Individual AEs were equally distributed above and below the mean population Cmax and AUCinf for the dataset.

Conclusion
In general, adverse events for FT218 occurred around Tmax. There was no clear population toxicokinetic range for when AEs occur with FT218, but mostly individual thresholds. Since it appears AEs are related to Cmax, and FT218 only has one Cmax compared to two with the currently available product, it is hypothesized that FT218 will have a favorable safety profile compared to twice-nightly dosing.

Support
This work was supported by Avadel Pharmaceuticals