bluuebunny/crossref_metadata_2025_split huggingface dataset:
0592 Accelerometer Control Performs Comparable to Pressure Sensor Control of Hypoglossal Nerve Stimulation Timing
Authors: Roy Asim , Doghramji Karl , Manchanda Shalini , Byrd Israel , Manne-Nicholas James , Thorp Chris , Dieken Dave , Cornelius Jason 
Published: April 2024

Abstract

Introduction
The hypoglossal nerve stimulation (HNS) system from Inspire Medical Systems, Inc (Golden Valley, MN) monitors respiration with a pressure sensor to deliver stimulation during inspiration. The sensor is embedded in a lead that is typically implanted in the second intercostal space and anterior to the generator. Inspiratory phase overlap fraction (IPOF) is the fraction of the inspiration phase concurrent with the stimulation burst. An accelerometer embedded in the generator to replace the implanted sensor lead could simplify the HNS system and implant procedure. To test whether an accelerometer control system performs comparably to the pressure sensor control system, we compared the IPOF of the commercial HNS system to that derived from an externally mounted accelerometer.

Methods
Fifty-six patients previously implanted with an HNS system (8 Inspire II, 48 Inspire IV) underwent a polysomnogram (PSG) while also wearing two accelerometers on their chest (approximately 5 cm below each the left and right clavicle, a typical implant location). The commercial system stimulation timing was exported and time-aligned with the PSG waveform to calculate the commercial system’s IPOF. The accelerometer waveforms were exported and time-aligned with the PSG respiration sensor, then the sensing algorithm was applied to the accelerometer waveforms to determine stimulation timing and calculate the accelerometer system’s IPOF. IPOF is reported as mean ± standard deviation [95% confidence interval for the mean]. The entire cohort was used in commercial system analysis but was divided into separate groups for accelerometer algorithm tuning and validation.

Results
Commercial system IPOF was 78%±7%, 95%CI [76%-79%] (n=56, 298 sleep hours). Accelerometer system IPOF was 86%±6%, 95%CI [84%-88%] in the tuning group (n=26, 133 sleep hours) and 83%±8%, 95%CI [80%-85%] in the validation group (n=30, 165 sleep hours).

Conclusion
Results from this study demonstrate an externally worn accelerometer based IPOF is comparable to the pressure sensor based IPOF of the implanted HNS system. This suggests an accelerometer control system embedded in the generator could replace the implanted pressure sensor to provide at least equivalent stimulation delivery.

Support (if any)
This study was funded by Inspire Medical Systems. Inspire employees contributed to the study execution and data analysis.
0596 Comparative Analysis of Continuous Positive Airway Pressure and Hypoglossal Nerve Stimulation
Authors: Khan Taimoor , Heinzinger Catherine , Foldvary-Schaefer Nancy , Mehra Reena , Lee Kent , Lundeen Max , Araujo Matheus Lima Diniz 
Published: April 2024

Abstract

Introduction
Continuous positive airway pressure (CPAP) adherence represents a pervasive, multifactorial challenge. Hypoglossal nerve stimulation (HNS) is an alternative treatment for moderate-severe obstructive sleep apnea (OSA) for those who are CPAP-intolerant. We hypothesized differential predictors of therapy adherence and greater adherence with HNS versus CPAP.

Methods
We compared adherence and its predictors in patients from the Cleveland Clinic HNS registry (cloud-based data monitoring) versus those on CPAP from the HomePAP study at the 1st and 3rd month timepoints. Linear models assessed age, sex and body mass index (BMI) as 1- and 3-month HNS and CPAP adherence predictors. Propensity score matching (1:1) without replacement and t–tests were used to compare adherence across the groups. Propensity scores were estimated with support vector machine using age, sex, BMI and Epworth Sleepiness Scale (ESS) at baseline.

Results
We analyzed data from n=63 HNS patients (age:57.9±10.0 years, 60% male, body mass index (BMI):28.8 ±3.3 kg/m2), ESS score:8.83±4.69) and n=126 CPAP patients from the HomePAP study (age:49.8±11.9 years, 63% male, BMI:39.1±9.43 kg/m2, ESS score:14.3±3.8). At 1-month, female sex was associated with increased HNS therapy usage (1.20, SE:0.47, p&lt; 0.01); a finding not observed at 3-months. Propensity score-matched analysis included 28 HNS patients (age: 53.6± 9.9 years, 67% male, BMI:30.7± 2.6 kg/m2, ESS:11.4± 3.7) and 28 CPAP patients (age:58.5± 9.6 years, 85% male, BMI:31.2± 4.0 kg/m2, ESS:12.2± 3.6). At 1-month (HNS n=28, CPAP n=27), usage was 3.90±1.0 hours for CPAP and 6.97±1.09 hours for HNS (p&lt; 0.01). At 3-months (HNS N=27, CPAP N=24), usage was 4.38±1.87 (SD) hours for CPAP and 6.44±1.96 hours for HNS (p&lt; 0.01).

Conclusion
In this comparative analysis, we identify female sex as a factor associated with early adherence to HNS, findings not observed with CPAP. Using a rigorous approach to address baseline differences, we identify a substantial increased level of adherence in HNS versus CPAP therapy of approximately 2-3 hours which persisted until 3 months. Future investigation should focus on assessing HNS versus CPAP adherence-related improvement in clinical outcomes.

Support (if any)
NIH grant R21HL170206.
0599 Effects of Proximal HGN Stimulation in HTN Subjects with Moderate to Severe OSA: A 5-Year Analysis of the THN3 RCT
Authors: Schwartz Alan , Jacobowitz Ofer , Mickelson Samuel , Miller Mitchell , Oliven Arie , Certal Victor , Hopp Martin , Winslow David , Huntley Tod , Nachlas Nathan , Gillespie M Boyd , Weeks Brian , Lovett Eric , Malhotra Atul , Maurer Joachim 
Published: April 2024

Abstract

Introduction
Hypoglossal nerve stimulation (HGNS) improves sleep-disordered breathing (SDB), oxygenation, and quality of life (QOL) in obstructive sleep apnea (OSA), but to date, has not been shown to improve cardiovascular outcomes. The THN3 randomized, controlled trial of proximal HGNS included subjects with office systolic blood pressure (SBP) ≤160mmHg or diastolic pressure ≤100mmHg. In post-hoc analyses, we examined whether antihypertensive effects of HGNS could be identified in a hypertensive THN3 subgroup.

Methods
THN3 participants (AHI 20-65/hr; BMI ≤ 35 kg/m2, no drug-induced sleep endoscopy screening) were followed for 5 years after HGNS system implant. In addition to annual measurements of SDB and QOL, BP was measured at every visit. Normotensive and hypertensive subgroups were fit to a linear mixed model with quadratic terms and 2 latent classes in order to estimate group BP trajectories from the time of HGNS initiation. Differences in baseline characteristics between classes were also evaluated.

Results
Of 137 subjects with evaluable data, 130 (95%) belonged to a normotensive class. SBP remained stable in this group, with estimated SBP mean (95%CI) of 128.9 (127.2,130.6), 129.2 (127.7,130.8), 129.5 (127.7,131.3), 129.7 (127.8,131.6), 129.8 (127.9,131.8), and 129.9 (127.3,132.5) mmHg at Baseline followed by Years 1-5 measurements, respectively. The remaining 7 (5%) subjects belonged to a hypertensive class. SBP decreased over time in these hypertensive patients with HGNS, with the estimated SBP mean trajectory of 156.4 (145.5,167.3), 142.8 (133.8,151.8), 134.8 (125.5,144.2), 132.5 (123.2,141.7), 135.7 (126.5,144.9), and 144.5 (132.2,156.9) mmHg. Aside from SBP, the groups differed at Baseline in average oxygen desaturation index (37.5±10.1 vs. 32.6±3.3/hr, normotensive vs. hypertensive) and percentage of sleep time with oxygen saturation &lt; 90% (11.9±9.8 vs. 4.7±3.8%). No meaningful differences were detected in Baseline age, sex or BMI.

Conclusion
Amelioration of OSA and nocturnal hypoxemia with proximal HGNS may improve SBP in hypertensives with moderate to severe OSA. If so, HGNS may improve long-term cardiovascular outcomes. Future analyses in the ongoing OSPREY and other trials should determine whether HGNS predicts reductions in SBP.

Support (if any)
LivaNova
0602 Application of a Physiology Based OSA Endotype Model to Predict Oral Appliance Outcomes Using Home Sleep Study Data
Authors: Eckert Danny , Dutta Ritaban , Levendowski Daniel 
Published: April 2024

Abstract

Introduction
Prediction of oral appliance therapy (OAT) response to treat obstructive sleep apnea (OSA) remains a major clinical challenge (currently ~50% or less depending on treatment definition). Recent physiology-based studies indicate that different combinations of pathophysiological traits or “OSA endotypes” are associated with OAT outcomes. However, methodologies to identify OSA endotypes to inform patient selection for OAT have largely been limited to in-laboratory and detailed physiology testing which limits clinical translation potential. Accordingly, we recently developed a physiology-based model that uses standard polysomnography and clinical data to predict OAT outcomes with correct OAT treatment classification in ~60 to &gt;90% of cases depending on the treatment outcome definition (Dutta et al, J Clin Sleep Med, 2022). Here we applied this model to a large clinical cohort who had a home-based diagnostic study to determine the proportion of people estimated to respond to OAT.

Methods
Model based OAT predictions were performed using clinical data (i.e., age and BMI) plus standard sleep study outputs from &gt;6,500 consecutive home-based diagnostic studies (Sleep Profiler PSG- Advanced Brain Monitoring). All participants had an apnea/hypopnea index (AHI) &gt;5 events/h. The proportion of participants who were estimated to respond to OAT according to the model was calculated across three commonly used treatment outcome definitions: 1) AHI&lt; 5, 2) AHI&lt; 10 events/h and 3) 50% reduction in AHI.

Results
On average, participants (39% female) were middle-aged (49±15 years ([Mean±SD]), had moderately severe OSA (AHI=28±23 events/h) and were obese (BMI=32±7 kg/m2). ~10% were predicted to fully respond (AHI&lt; 5 events/h) to OAT, ~43% to achieve an AHI&lt; 10 events/h and 42% to have a 50% reduction in AHI. Conversely, ~41% of participants were predicated to not respond to OAT across all 3 treatment definitions.

Conclusion
While further prospective validation is required, these real-world data suggest that application of a novel physiology based OSA endotype algorithm using standard clinical and home sleep study information may be helpful to identify successful candidates for OAT (and vice versa) in a substantial proportion of people diagnosed with OSA with greater accuracy that current clinical practice.

Support (if any)
DJE is funded by a National Health and Medical Research Investigator Grant (1196261).
0617 Efficacy of Nasal Expiratory Positive Airway Pressure in Veterans with Obstructive Sleep Apnea
Authors: Tsai Tiffany , Olteanu Nicoleta , Liu Zi Yu , Wilson Brigid , Strohl Kingman , Gandotra Kamal , Ashraf Fareeha , Chiang Ambrose 
Published: April 2024

Abstract

Introduction
Nasal expiratory positive airway pressure (EPAP) stands as a viable therapeutic solution for individuals with obstructive sleep apnea (OSA). Bongo Rx (AirAvant Medical, Deerfield Beach, Florida) has obtained FDA clearance for treating patients with mild-to-moderate OSA despite limited publication. Amidst the global continuous positive airway pressure (CPAP) shortage, veterans with mild to moderate OSA were presented with the option of Bongo Rx. Individuals who opted to use Bongo Rx for a minimum of one month were subjected to WatchPAT testing (Itamar/ZOLL, Atlanta, Georgia) while on Bongo Rx. This retrospective study aimed to assess the efficacy of Bongo Rx in veterans who underwent follow-up WatchPAT within 12 months from the initial baseline.

Methods
Retrospective chart review. OSA-related measures were compared before and after Bongo Rx using paired t-tests to compare means or Wilcoxon signed-rank tests when values were highly skewed.

Results
Twenty-two veterans with OSA met the eligibility criteria and their data were analyzed. Mean age 60; M:F ratio 16:6; BMI 33.5; 15 White (68%), 6 Black (27%), and 1 Pacific Islander (5%); 10 veterans had mild OSA (45%), 10 moderate OSA (45%), and 2 severe OSA (9%). Overall, Bongo Rx reduced mean WatchPAT Apnea-Hypopnea Index (AHI) by 40% (baseline AHI 16.6 and Bongo-AHI 10.0, p=0.0007), mean respiratory disturbance index (RDI) by 41% (baseline RDI 19.4 and Bongo-RDI 11.5, p=0.0003), and mean oxygen desaturation index (ODI) by 31% (baseline ODI 14.4 and Bongo-ODI 9.9, p=0.0038). Mean SpO2 nadir increased by 2.4% (baseline SpO2 nadir 82% and Bongo SpO2 nadir 84%), median time with SpO2 under 88% (T88) decreased by 58% (baseline T88 1.2 min and Bongo-T88 0.5 min), and these changes were not statistically significant (all p&gt;0.05). Notably, the two severe OSA cases showed 73% and 42% improvement of AHI (baseline AHI 37.0 and Bongo-AHI 7.7 in one, and baseline AHI 38.4 and Bongo-AHI 22.2 in another).

Conclusion
Nasal EPAP with Bongo Rx seems efficacious in reducing AHI, RDI, and ODI in patients with mild to moderate OSA. The efficacy of Bongo Rx in severe OSA should be explored in future research. Further investigation into tolerance and adherence is warranted.

Support (if any)
0619 Depression and Treatment Use in Patients with Obstructive Sleep Apnea on Glucagon-Like Peptide 1 Receptor Agonists
Authors: Cole Kate , Dexter R , Cameron Ann , Woodford Caleb , Alpert Naomi , McConnell Will , Sterling Kimberly , Cistulli Peter , Malhotra Atul , Pépin Jean-Louis 
Published: April 2024

Abstract

Introduction
Depression and obesity are both prevalent among patients with obstructive sleep apnea (OSA). Treating OSA has been shown to improve depressive symptoms. Routine treatment for OSA often includes positive airway pressure (PAP) therapy combined with weight management strategies, including glucagon-like peptide 1 receptor agonists (GLP-1s), which have been approved to treat type 2 diabetes (T2D) and obesity. Little is known about the relationship between GLP-1 use and OSA and depression treatment patterns, or how these may be affected by depression status and gender.

Methods
Administrative insurance claims from 2014-2023 for adult patients with OSA who filled a GLP-1 prescription with ≥1 year of enrollment before and after the first recorded GLP-1 fill (index date) were analyzed. Depression was defined based on ICD-10 diagnosis codes within the year prior to index. Antidepressant use and OSA treatment in the year pre- and post-index were described.

Results
Of 151,529 patients included (mean age 54.3 years; 48.9% female), 26.3% had depression prior to index. Those with depression were more often women (66.2% vs 42.8%). Prevalence of Medicaid insurance (40.9%) and class III obesity (65.7%) was highest among women with depression, compared to men or those without depression. T2D was common (85.7% overall), with higher prevalence among men. Prior to index, approximately 53% of women and 56% of men had evidence of PAP therapy; this decreased slightly to approximately 48% and 51%, respectively, in the year after index, regardless of depression status. Among patients with depression, prevalence of ≥1 antidepressant prescription was consistent pre- and post-index, but higher among women than men in both periods (pre: 86.0% vs 81.0%; post: 86.0% vs. 80.4%). In the year after index, approximately 41% of women and 39% of men discontinued GLP-1s, regardless of depression status.

Conclusion
Among patients with OSA starting GLP-1 therapy, prevalence of PAP-related claims were similar in patients with and without depression and by gender. Antidepressant use remained consistent among men and women with depression. Future research should evaluate the impact of GLP-1 use on treatment patterns by indication (T2D or obesity/overweight).

Support (if any)
ResMed
0628 Consistent Efficacy of Once-Nightly Sodium Oxybate Across Patient Demographic and Baseline Disease Characteristics
Authors: Thorpy Michael , Roth Thomas , Kushida Clete , Morse Anne , Harsh John , Ortiz Luis , Gudeman Jennifer , Dauvilliers Yves 
Published: April 2024

Abstract

Introduction
Once-nightly sodium oxybate (ON-SXB; LUMRYZ™) was investigated in patients with narcolepsy type 1 (NT1) or 2 (NT2) in the phase 3 REST-ON trial; treatment with 6, 7.5, and 9 g demonstrated significant improvements vs placebo (all P&lt; 0.001) for the coprimary endpoints of change from baseline in mean sleep latency on the Maintenance of Wakefulness Test (MWT), Clinical Global Impression-Improvement (CGI-I) rating, and weekly number of cataplexy episodes (NCA), and the secondary endpoint Epworth Sleepiness Scale (ESS) score. This post-hoc analysis assessed ON-SXB efficacy in various subgroups.

Methods
REST-ON (NCT02720744) participants aged ≥16 years with NT1 or NT2 were randomized 1:1 to ON-SXB (4.5 g, 1 week; 6 g, 2 weeks; 7.5 g, 5 weeks; 9 g, 5 weeks) or placebo for 13 weeks. Least squares mean differences (LSMDs) in changes from baseline for ON-SXB vs placebo for mean sleep latency on MWT, NCA (NT1 only), and ESS, and odds ratios for “much”/“very much” improved on CGI-I, were compared among baseline demographic (age, sex, race, body mass index [BMI] category) and narcolepsy disease characteristic (NT1/NT2; concomitant alerting agent use) subgroups.

Results
The modified intent-to-treat population included 190 participants (ON-SXB, n=97; placebo, n=93). LSMDs for ON-SXB 9 g vs placebo in change from baseline on the MWT at week 13 revealed significant improvements (P&lt; 0.05) for subgroups based on age, sex, race, BMI, narcolepsy type, and alerting agent/no alerting agent use. Odds ratios were significant in favor of ON-SXB 9 g vs placebo for “much” or “very much” improved on CGI-I at week 13 (P&lt; 0.05) for both low/high age, female sex, white/non-white, high BMI, NT1, and alerting agent/no alerting agent use. LSMDs were significant in favor of ON-SXB 9 g vs placebo for change from baseline in NCA (P&lt; 0.05) in all subgroups, except non-white and male. For the ESS, all subgroups exhibited significant improvements (P&lt; 0.05) with ON-SXB 9 g vs placebo, except NT2. Comparable differences were found with the 6-g dose at Week 3 and the 7.5-g dose at Week 8.

Conclusion
Post-hoc subgroup analyses demonstrate the robust efficacy of ON-SXB across demographic and clinical subgroups.

Support (if any)
Avadel Pharmaceuticals
0630 Efficacy of Sodium Oxybate in Adults with Idiopathic Hypersomnia : A Randomized Placebo-controlled Trial
Authors: Dauvilliers Yves , Chenini Sofiene , Thobois ophélie , Rassu Anna Laura , Denis claire , Guiraud Lily , Jaussent Isabelle , Barateau Lucie 
Published: April 2024

Abstract

Introduction
Idiopathic hypersomnia (IH) is a rare central hypersomnolence disorder characterized by excessive daytime sleepiness, prolonged nighttime sleep and sleep inertia. The efficacy and safety of low-sodium oxybate was reported in a phase 3 randomized withdrawal study in IH on Epworth Sleepiness scale (ESS) and Idiopathic Hypersomnia Severity Scale (IHSS). We conducted a phase 3, monocentric, double-blind, randomized, parallel group, placebo-controlled trial of sodium oxybate (SXB) in IH with ESS, IHSS and Maintenance of Wakefulness Test (MWT) assessment.

Methods
Eligible participants 18–60 years of age with IH according to criteria (ICSD3) with ESS ≥14 were randomly assigned to treatment with SXB or placebo in a 1:1 ratio. After a 2-week screening without any CNS drugs and never exposed to oxybate, patients started a 6-week individual twice nightly up-titration scheme from 4.5 g to a maximum of 9 g, treatment was administered at stable dose (6g or 9g) for 2 weeks, followed by a 1-week taper period. The primary endpoint was the mean change from baseline to week 8 on ESS. Key secondary endpoints were safety, changes in average sleep latency on the MWT and IHSS.

Results
Between October 2018 and January 2023, we screened 48 patients, 45 were randomized (36 females, mean age 29.0±7.5, ESS 16.5±2.7, 40 having long sleep time; 22 assigned to SXB and 23 placebo), and 40 (19 receiving SXB and 21 placebo) completed the double-blind period. Between-group differences (SXB vs placebo) for the mean [IC95%] change in ESS from baseline to endpoint were -6.54 [-9.35;-3.73] (p=0.004). Between-group differences for the average sleep latency on the MWT from baseline to endpoint were 13.87 [8.35 ;19.39] (p=0.0001), and for IHSS -10.87 [-15.71;-6.03] (p=0.0004). Treatment-emergent adverse events were reported in 17 (77%) of 22 patients with SXB and 7 (30%) of 23 with placebo. The most frequently reported adverse events were nausea, headache, and dizziness.

Conclusion
SXB resulted in a clinically meaningful improvement in adults with IH, reducing excessive sleepiness on the ESS, improving wakefulness on the MWT and decreasing IH severity on IHSS after 8 weeks. The safety profile was similar to that previously reported with SXB. NCT03597555

Support (if any)
Grant from Jazz Pharmaceuticals
0633 Efficacy and Safety of Low-Sodium Oxybate in Narcolepsy Patients With/Without Psychiatric/Neurologic Comorbidities
Authors: Chepke Craig , Cutler Andrew , Watson Nathaniel , Candler Shawn , Fuller Douglas , Measey Thomas , Scheckner Brian , Akerman Sarah , Macfadden Wayne 
Published: April 2024

Abstract

Introduction
Prior studies report high incidences of psychiatric and/or neurologic comorbidities in patients with narcolepsy. Low-sodium oxybate (LXB; Xywav®) is an FDA-approved treatment for cataplexy or excessive daytime sleepiness in patients ≥7 years old with narcolepsy and for adults with idiopathic hypersomnia. This post hoc analysis of a phase 3 trial (NCT03030599) assessed LXB efficacy and safety in participants with narcolepsy with or without a medical history of psychiatric and/or neurologic comorbidities.

Methods
Participants were adults (18‒70 years) with narcolepsy with cataplexy. Participants optimized/titrated their LXB dose (up to 12 weeks) before a 2-week stable-dose period. During a 2-week double-blind randomized-withdrawal period, participants were either switched to placebo or continued LXB. Epworth Sleepiness Scale (ESS), average weekly number of cataplexy attacks, Patient Global Impression of Change (PGIc) scores, Patient Health Questionnaire-9 (PHQ-9) scores, and treatment-emergent adverse events (TEAEs) were evaluated in participants with and without psychiatric and/or neurologic comorbidities.

Results
Of 201 participants, 84 reported baseline comorbidities (most commonly depression, migraine headaches, anxiety, and headache [non-migraine]). Imbalances between subgroups were observed with regard to sex, race, ethnicity, and body mass index. Participants randomized to placebo in both subgroups showed worsening (increases) in ESS scores compared with participants who continued with LXB treatment (least squares mean differences, LXB vs placebo [95% CI], with comorbidities: −3.7 [−5.6, −1.9], P=0.0001; without comorbidities: −2.0 [−3.5, −0.6]; P=0.0050). Participants randomized to placebo in both subgroups had increased weekly cataplexy attacks compared with those continuing LXB (location shift, LXB vs placebo [95% CI], with comorbidities: −4.0 [−7.0, −1.1], P=0.0026; without comorbidities: −3.5 [−9.1, −1.1], P&lt; 0.0001). Participants randomized to placebo in both subgroups showed worsening in PGIc scores compared with LXB (P&lt; 0.0001, for both). Symptoms of depression, as measured by PHQ-9 scores, remained stable in both subgroups. TEAEs and serious TEAEs occurred in 69 (82.1%) and 1 (1.2%) participants with comorbidities, and 84 (71.8%) and 3 (2.6%) without comorbidities, respectively.

Conclusion
In this post hoc analysis of a phase 3 trial in patients with narcolepsy, the efficacy and safety of LXB in participants with psychiatric and/or neurologic comorbidities were similar to those in participants without such comorbidities.

Support (if any)
Jazz Pharmaceuticals