bluuebunny/crossref_metadata_2025_split huggingface dataset:
0549 Positive Airway Pressure for Obstructive Sleep Apnea in Systolic Heart Failure Patients Reduces Healthcare Resource Utilization
Authors: Kuniyoshi Fatima Sert , Malhotra Atul , Cole Kate , Malik Anita , Pépin Jean-Louis , Cistulli Peter , Benjafield Adam , Somers Virend 
Published: May 2023

Abstract

Introduction
The prevalence of obstructive sleep apnea (OSA) is high in patients with systolic heart failure (HFrEF) and has been associated with poor prognosis in this patient population. The impact of positive airway pressure (PAP) therapy in patients with OSA and HFrEF remains unclear. This retrospective study sought to investigate the association between 1-year adherence to PAP therapy and healthcare resource utilization (HCRU) in patients with newly diagnosed OSA and comorbid HFrEF.

Methods
A national sample of administrative claims data linked to objective PAP therapy usage was used for this analysis. Included patients either had two healthcare encounters or one hospitalization with a systolic heart failure ICD-10 diagnosis code the year prior to being diagnosed with OSA and initiated on PAP therapy. HCRU was measured as a composite outcome of hospitalizations, and emergency room (ER) visits. Propensity score matching was used to create well-balanced groups with differing PAP adherence levels to assess the association with 1-year HCRU outcomes. Risk-adjusted models were used to generate the number needed to treat (NNT) that referred to the number of patients that need to become adherent to PAP from non-adherent to avoid 1 visit.

Results
We identified 3,182 patients with OSA and comorbid HFrEF, and after propensity score matching, 738 patients remained in each group (adherent vs. non-adherent). After 1 year of PAP therapy, adherent patients had fewer visits than non-adherent patients (0.92 vs. 1.15 visits per subject, p = 0.006), which was driven by a 24% reduction in ER visits for adherent patients. Composite hospitalization and ER visit costs were lower in adherent versus non-adherent patients ($3,500 vs. $5,879, p=0.03). The NNT for the entire cohort to avoid one visit was 1.5 patients.

Conclusion
HFrEF patients with comorbid OSA who were adherent to PAP therapy for 1 year have fewer composite hospitalizations and ER visits than patients that were not adherent. These results highlight the clinical and economic benefits of treating OSA in HFrEF patients.

Support (if any)
Funding Source: ResMed
0551 Predicting Daytime Alertness Impairment in Obstructive Sleep Apnea
Authors: Warda Ali , Lennox Victoria Mariah , Nguyen Tu , Ghosh Shanta , Basu Sanjib , Younes Magdy , Carley David W , Prasad Bharati , Gerardy Bethany 
Published: May 2023

Abstract

Introduction
Obstructive sleep apnea (OSA) reduces daytime alertness leading to social and occupational impairment. The Maintenance of Wakefulness Test (MWT), a gold-standard test for daytime alertness, is time-consuming and not routinely available in clinical practice. We examined EEG-based and clinical parameters derived from diagnostic polysomnography (PSG) as predictors of alertness impairment in adults with OSA.

Methods
Eighty-two participants with untreated OSA on diagnostic PSG (apnea hypopnea index, AHI ≥5/hour), enrolled in a two-center clinical trial were included. The day following PSG, each participant completed four 40-minute MWT and four 10-minute Psychomotor Vigilance Tests (PVT). The outcomes were MWT mean sleep latency (MSL) and PVT lapses (reaction time ≥500 milliseconds, square root transformed). Three multiple linear regression models were used: 1. “standard predictors” (total sleep time, TST, percent REM and slow wave sleep, AHI, time &lt; 90% oxygen saturation, and arousal index), 2. “novel predictors” derived by spectral analysis and averaged across right and left central EEG (normalized EEG power, odds ratio product; ORP parameters, and spindle characteristics), and 3. combined standard and novel predictors. Age, sex, and body mass index (BMI) were included in each model, and backward elimination (step AIC) was used for models 2 and 3.

Results
Participants were middle-aged (mean ± standard deviation, SD 53.5±8.7 years), with moderate OSA (AHI 33.8±18.2) and daytime sleepiness (Epworth Sleepiness Scale 11.7±3.9), and 86% were men. The adjusted r2 for MSL were: model 1=0.09, model 2=0.16, and model 3=0.27, and PVT lapses were: model 1=0.09, model 2=0.31, and model 3=0.34. For MSL, the significant predictors in model 3 included TST (t-statistic -3.59, p=0.0007), REM% (2.51, p=0.01), ORP-9 (2.95, p=0.004), ORP NREM (-3.15, p=0.002), spindle frequency (-2.95, p=0.004), and normalized EEG power (-2.59, p=0.01). For PVT lapses, model 3 predictors included 2.25-2.5 ORP% (-2.91, p=0.005), normalized EEG power (3.22, p=0.002), spindle power (-4.30, p&lt; 0.0001), spindle frequency (2.83, p=0.006), and sex (men vs. women, -2.56, p=0.01).

Conclusion
We have identified several novel PSG EEG-based predictors of impaired daytime alertness in OSA that will improve occupational evaluation and prognostication in OSA after future validation.

Support (if any)
National Institutes of Health, UM1-HL112856, UL1TR001422, and UL1TR002003.
0564 The mechanism of deficits in cognition of OSA: plasma amyloid-beta and tau protein level by the intervention design
Authors: Lin Chia-yu , Liu Wen-Te , Yang Chien-Ming , Lee Yu-Chuan , Lien Ting-chu , Kao Yu-Hsuan 
Published: May 2023

Abstract

Introduction
Obstructive sleep apnea syndrome (OSAS) was shown to impair neurocognitive functioning, which was often attributed to hypoxia and sleep fragmentation. More recently, increased accumulation of amyloid-beta and tau protein in OSAS patients have gotten research attention and have been considered to be a possible cause of neurocognitive impairments. Positive airway pressure (PAP) treatment has been found to improve cognitive functioning in OSAS patients. The current study further explored the association of the effects of PAP treatment on neurocognitive and plasma amyloid-beta (Aβ) and tau protein levels.

Methods
Sixteen OSAS patients (M:F=10:6; age average = 53.35, SD = 10.43) participated in the study. A package of neurocognitive tasks (CPT-III, verbal paired association task, PASAT-R, and semantic verbal fluency) were administered and blood sample was collected both before and after a 3-month period of PAP intervention. The total tau and Aβ 42 levels in the patients’ plasma were quantified using an ultrasensitive immunomagnetic reduction assay.

Results
T-tests comparing cognitive performance before and after PAP treatment showed significant difference in total immediate recall score of verbal pair association task (t = 3.412, p = .002) and near significant differences in commission error on CPT-III (t = -.357, p = .097) and total score on PASAT-R (t = 1.35, p = .099). Other neurocognitive tasks as well as Aβ and tau proteins showed no significant changes. However, the change of Aβ after treatment correlated significantly with the improvement on the first immediate recall sequence (r = -.64, p = .005), and tau protein level correlated with the score on 2-sec-ISI subscale of PASAT-R (r = -.45, p = .048).

Conclusion
The present study showed that three months of PAP treatment was effective in improving immediate memory, but not in other cognitive functions or Aβ and tau protein levels. Moreover, some changes in memory and executive function were associated with decrease of Aβ and tau proteins. The preliminary results suggest that the neurocognitive impairment in OSAS patients might be partially associated with accumulation of Aβ and tau proteins. Future studies are needed to further confirm the findings.

Support (if any)
0570 Use of the ExVent Accessory with the O2Vent Optima Oral Appliance for the Treatment of Obstructive Sleep Apnea – A Clinical Trial
Authors: Sharma Sat , Conflitti Antonella 
Published: May 2023

Abstract

Introduction
The ExVent is an optional accessory to the O2Vent Optima mandibular advancement device (MAD) and provides oral Expiratory Positive Airway Pressure (EPAP). Oral EPAP with the ExVent is designed to provide upper airway support via similar mechanisms of action of nasal EPAP devices in commercial distribution, e.g., passive dilatation of the airway, which reduces flow limitation. Nasal EPAP devices are in commercial distribution as stand-alone therapies for the treatment of OSA. The oral EPAP provided by the ExVent accessory is designed to augment the OSA therapy provided by the O2Vent Optima.

Methods
This is a prospective, open-label, single-arm study conducted at 3 sites. Subjects who have been diagnosed with mild to moderate OSA (i.e., AHI ≥ 5 and ≤ 30) were included. Screening Phase The subjects completed a PSG study to obtain the baseline AHI and confirm a diagnosis of mild to moderate OSA Home Use Phase Subjects used the O2Vent Optima + ExVent for up to 3 months and logged usage hours. Subsequent to the Home Use Phase subjects underwent an in-lab PSG sleep night while using the O2Vent Optima + ExVent. Primary Effectiveness Outcome Measure: Change in AHI between baseline and the AHI measured during the in-lab PSG sleep night using O2Vent Optima + ExVent. Safety Outcome Measure: Adverse events will be summarized descriptively in terms of type and frequency

Results
Patients with mild to moderate OSA were treated with Optima MAD and ExVent for 3 months at 3 different sites in North America. Preliminary data analysis demonstrated that treatment with Optima MAD and ExVent reduced AHI from 13.5±6.4/hr to 6.6±4.5/hr (p&lt; 0.05), average 58% reduction in AHI. The lowest oxygen during sleep increased from 84.6±2.7% to 88.6±2.9% (p&lt; 0.05). Overall success rate (&gt;50% reduction in AHI) with treatment was 80%. During the trial patients on treatment with Optima MAD and ExVent demonstrated no excessive adverse events or device malfunction.

Conclusion
The clinical trial confirmed successful treatment with combined use of O2Vent Optima MAD and oral Expiratory Positive Airway Pressure accessory - ExVent in patients with mild to moderate OSA. Treatment was well tolerated with no excessive adverse effects.

Support (if any)
0571 Utilization of Self-Efficacy Measure of Sleep Apnea (SEMSA) questionnaire to Predict CPAP Adherence
Authors: Nguyen Tu , Lennox Victoria Mariah , Warda Ali , Mechineni Ashesha , Mann Harkirat , Pattisapu Ani , Prasad Bharati 
Published: May 2023

Abstract

Introduction
The Self-Efficacy Measure for Sleep Apnea (SEMSA) is a self-administered questionnaire developed to assess pretreatment expectancies between obstructive sleep apnea (OSA) and continuous positive airway pressure (CPAP) therapy in adults. Higher values on the three sub-scales of the SEMSA suggest a greater perceived risk of having OSA, more positive beliefs regarding the outcomes of CPAP therapy, and a greater willingness to use CPAP. We examined the utility of the SEMSA in predicting CPAP adherence in a diverse urban population.

Methods
SEMSA was completed by patients presenting for polysomnography (PSG) over three months. We collected demographic data, body mass index (BMI), marital status, social vulnerability index (SVI), apnea hypopnea index (AHI), and 30-day adherence data from CPAP device download following the initiation of therapy. The outcomes were CPAP average usage per day in the first 30 days (minutes) and the percentage of days with usage over 4 hours. Stata v15 was used for multivariable linear and logistic regression analyses.

Results
One hundred eighty-eight patients completed the SEMSA, of which 101 were diagnosed with OSA and initiated CPAP. The study sample was middle-aged (mean ± SD, 52.5±13.3 years), with variable OSA severity (AHI 44.8±39.5) and high levels of obesity (BMI 39.5±12.4) and racial diversity (61% Black, 10% White, 18% Hispanic, and 10% other), 47% were men, and 33% were married. The multivariable models found that after adjusting for age, sex, race, marital status, SVI, ESS, and AHI, the SEMSA score was a significant predictor of average CPAP use (linear regression, t-statistic=3.19, p=0.002) and ≥70% CPAP use of ≥4 hours per day (logistic regression, t-statistic=3.23, p=0.002, area under the curve; AUC=0.73).

Conclusion
The SEMSA score is a strong predictor of CPAP adherence in a diverse urban population. The patients with lower self-efficacy based on the SEMSA should be targeted for early CPAP adherence promoting education and interventions.

Support (if any)
0572 Weight reduction and the impact on apnea-hypopnea index: a meta-analysis
Authors: Malhotra Atul , Curtis Alexandra , Dunn Julia , Bunck Mathijs C , Bednarik Josef 
Published: May 2023

Abstract

Introduction
The occurrence of obstructive sleep apnea (OSA) is strongly associated with obesity. Behavioral, pharmacological, and surgical interventions that promote weight reduction can reduce OSA severity and improve other common obesity related complications and quality of life. While the relationship between weight reduction and apnea-hypopnea index (AHI) improvement has been documented, it does not seem to have been quantified adequately. The objective of this analysis was to quantify the association between percent change in body weight and percent change in AHI using results from the literature.

Methods
A literature search identified 13 studies with AHI and weight measurements before and after weight intervention in people living with obesity and OSA; 6 studies from bariatric surgery, 4 studies from diet and exercise intervention, and 3 studies from anti-obesity medications (including 2 placebo-controlled randomized clinical trials). A polynomial and a linear meta regression model as well as 95% prediction intervals were used to assess the relationship between % weight change from baseline and % change in AHI from baseline.

Results
Both the polynomial and linear models show, on average, weight reduction in patients living with obesity and OSA has a clinical benefit in reducing AHI. The linear meta-regression model that we developed suggests a mean AHI decrease of 2.6% per 1% weight reduction. As the prediction intervals are relatively wide, a precise relationship could not be established. For example, based on the linear model for a patient with 20% weight reduction we expect to see a mean 52.8% reduction in AHI with a 95% prediction interval (89.8%, 15.8%) AHI reduction.

Conclusion
Evidence shows that intentional weight reduction in people living with obesity and OSA results in improvements in OSA severity, and this was confirmed by our meta-analysis and modeling. The model shows that the degree of AHI improvement is dependent on the magnitude of weight reduction. However, establishing a precise relationship between percent change in AHI and percent weight reduction is challenging given the sparsity of data, variability in populations studied, and variability in AHI change following weight reduction.

Support (if any)
Eli Lilly and Company
0573 Application of AASM Clinical Significance Thresholds to Once-Nightly Sodium Oxybate for Improvement in Narcolepsy Symptoms
Authors: Roth Thomas , Thorpy Michael , Kushida Clete , Morse Anne , Dubow Jordan , Gudeman Jennifer , Dauvilliers Yves 
Published: May 2023

Abstract

Introduction
Once-nightly sodium oxybate (ON-SXB; FT218), an investigational, extended-release treatment, was evaluated for the treatment of narcolepsy in adults in the phase 3 REST-ON clinical trial (NCT02720744). The 3 co-primary endpoints, mean sleep latency on the Maintenance of Wakefulness Test (MWT), Clinical Global Impression-Improvement rating, and weekly number of cataplexy attacks (NCA), and the secondary endpoint of Epworth Sleepiness Scale (ESS) score were significant for ON-SXB vs placebo at weeks 3 (6-g dose), 8 (7.5-g dose), and 13 (9-g dose; all P&lt; 0.001). These data were published after the cutoff for inclusion in the American Academy of Sleep Medicine (AASM) clinical practice guidelines for narcolepsy treatment; thus, REST-ON results were analyzed according to AASM clinical significance thresholds (CSTs).

Methods
Individuals with narcolepsy type 1/2 and age ≥16 years were randomized 1:1 to receive double-blind ON-SXB (4.5 g, 1 week; 6 g, 2 weeks; 7.5 g, 5 weeks; 9 g, 5 weeks) or matching placebo. For each dose (6 g, week 3; 7.5 g, week 8; and 9 g, week 13), least-squares mean (LSM) difference from placebo was calculated for change from baseline in mean sleep latency on the MWT, ESS score, and percentage reduction in NCA. As defined in the 2021 AASM guidelines, CSTs were the following changes vs placebo: MWT, ≥2-minute increase; ESS, ≥2-point decrease; and cataplexy, ≥25% decrease in NCA.

Results
190 participants (ON-SXB, n=97; placebo, n=93) were in the modified intent-to-treat population. On the MWT, difference in LSM change from baseline was 5.0, 6.2, and 6.1 minutes for ON-SXB 6, 7.5, and 9 g vs placebo, respectively. Differences in LSM change from baseline ESS scores were −2.1, −3.2, and −3.9 for ON-SXB 6, 7.5, and 9 g vs placebo, respectively. Differences in LSM percentage reduction in NCA were 26.0%, 34.2%, and 36.1% for ON-SXB 6, 7.5, and 9 g vs placebo, respectively.

Conclusion
Clinically significant improvement in excessive daytime sleepiness and cataplexy per AASM-established criteria was met with ON-SXB 6, 7.5, and 9 g doses. If FDA approved, ON-SXB will provide a once-nightly treatment for improving EDS and cataplexy in adults with narcolepsy.

Support (if any)
Avadel Pharmaceuticals
0574 Artificial Intelligence to Aid in Diagnosis of Type I Narcolepsy
Authors: Nygate Yoav , Rusk Samuel , Fernandez Chris , Winzurk Zac , Wickwire Emerson , Mignot Emmanuel , Watson Nathaniel F 
Published: May 2023

Abstract

Introduction
Accurate diagnosis of Type 1 narcolepsy (T1N) is cumbersome – involving clinical, biological, and electrophysiological components. Multiple sleep latency tests (MSLT) are central to diagnosis; however, current medications, sleep schedule, drug use, and testing environment can all compromise the interpretation of an MSLT. Incorrect MSLT results have devastating consequences for patients, including prolonged suffering from untreated T1N or adverse effects from unnecessary testing and therapies. Simple, accessible, accurate and cost-effective diagnostic solutions are needed. We evaluate automated methods to expand the diagnosis of T1N based on single night polysomnography (PSG).

Methods
The dataset included N=225 T1N patients and N=455 negative controls from 6 different cohorts. We evaluated two separate machine learning (ML) models for T1N detection: a supervised PSG-EEG based deep learning (PSG-DL) model focused on sleep microarchitecture, and a random forest (Sleep-RF) model based on traditional PSG report data. To measure performance, we calculated the area under the receiver operating characteristic curve (AUC-ROC) for each model and performed a feature importance analysis for the Sleep-RF model.

Results
AUC-ROC values were 0.960 and 0.878 for the PSG-DL and Sleep-RF models, respectively. Furthermore, the PSG-DL model produced a sensitivity and specificity of 84% and 94%, while the Sleep-RF model resulted in 75% and 83%. The feature importance analysis for the Sleep-RF model revealed these most important features: REM latency, sleep latency, total N3 time, and ratio of arousals in REM vs. non-REM.

Conclusion
ML methods automatically detected T1N in PSG-EEG with promising degrees of accuracy. These methods overcome common barriers to accurate diagnosis that can compromise the interpretability of an MSLT. Broad implementation of this method has potential to supplement the MSLT, increasing diagnostic detection rates and accuracy for T1N. Access to care can be broadened if T1N diagnosis were to occur anywhere a sleep EEG can be obtained, including the home setting, rather than being limited to in-center testing. This work has potential to further the developments of T1N detectors and assist in their widespread clinical adoption. Additional research is underway to help improve accuracy and ensure these methods are generalizable across platforms and clinical datasets.

Support (if any)
0589 Dose Titration of Once-Nightly Sodium Oxybate: Analysis of Interim Data From RESTORE
Authors: Roy Asim , Abaluck Brian , Stern Thomas , Kushida Clete , Dubow Jordan , Gudeman Jennifer 
Published: May 2023

Abstract

Introduction
FT218 (LUMRYZ™) is an investigational once-nightly sodium oxybate (ON-SXB) for treatment of adults with narcolepsy type 1 (NT1) or type 2 (NT2). The efficacy and safety of ON-SXB at doses 6, 7.5, and 9 g in patients with NT1/NT2 were confirmed in the phase 3 REST-ON clinical trial (NCT02720744). RESTORE is an ongoing, open-label extension/switch study to assess long-term safety and tolerability of ON-SXB (NCT04451668).

Methods
Individuals aged ≥16 years with NT1/NT2 are enrolled in Group A (participants who completed the REST-ON trial with no current oxybate use), Group B (participants who switched from twice-nightly immediate-release oxybates), or Group C (participants who are oxybate-naive). Initial ON-SXB dose is 4.5 g/night for Groups A/C and is the nearest equivalent or closest single dose to their previous nightly dose for Group B. Investigators may alter the nightly dose by 1.5 g/week (maximum, 9 g/night) based on effectiveness and tolerability.

Results
A total of 184 participants were enrolled (180, ≥1-dose) as of July 1, 2022. Most participants are white (n=150 [83.3%]) and female (n=122 [67.8%]), and mean age is 35 years. Most participants in Groups A/C (n=43/50 [86.0%]) increased from the 4.5-g initial dose and had 2–4 dose adjustments during initial titration (median [range], 3 [0–5]); 47% (17/36) are stable at 7.5 g. The most common initial doses in Group B were 7.5 g (50/130 [38.5%]) and 9 g (47/130 [36.2%]). Most in Group B reaching a stable dose maintained their initial dose (70/118 [59.3%]); 43 increased (36.4%) and 5 decreased (4.2%) their initial ON-SXB dose. In Group B, 49.1% (53/108) had no dose adjustments (median [range], 1 [0–5]) and 83.0% (n=39/47) who started at 9 g maintained this dose. Most common treatment-related adverse events (&gt;3%; safety population [n=180]) are nausea (11.7%), somnolence (6.7%), headache (5.0%), enuresis (5.0), dizziness (3.9%), tremor (3.9%), somnambulism (3.9%), and vomiting (3.3%).

Conclusion
Most study participants had successful titration of ON-SXB to a therapeutic and tolerable dose within 1 month. If granted final approval by the US Food and Drug Administration, ON-SXB will offer a once-nightly treatment for adults with narcolepsy.

Support (if any)
Avadel Pharmaceuticals