bluuebunny/crossref_metadata_2025_split huggingface dataset:
0535 Impact of hypoglossal nerve stimulation surgery alone on sleep disordered breathing and sleepiness
Authors: Strollo Patrick , Soose Ryan , Maurer Joachim , DeVries Nico , Vanderveken Olivier 
Published: May 2023

Abstract

Introduction
Hypoglossal Nerve Stimulation (HNS) is an established option for CPAP -intolerant obstructive sleep apnea (OSA) patients, with multiple studies demonstrating safety and effectiveness. There are known nightly variations in OSA severity. We aimed to determine if device implant alone (with therapy off) compared to baseline influenced sleep disordered breathing and daytime sleepiness.

Methods
This was a retrospective analysis of the STAR (Stimulation Therapy for Apnea Reduction) Trial, conducted from 2010-2016, that led to FDA approval HNS. Data was collected at a pre-implant screening, and post-implant prior to device activation (therapy off). Each visit included an attended polysomnography (PSG) and Epworth Sleepiness Scale (ESS). PSGs were scored by a central core lab.

Results
There were 126 participants (83% male), age 55 ± 10 years. The time between pre-implant baseline screening and device activation visit averaged 88 ± 29 days. BMI was 28 ± 3 at baseline and 28 ± 3 post-implant with therapy off. The pre and post-implant Apnea Hypopnea Index (AHI)s were similar (32 ± 9 vs 32 ± 9 events/hour, p=0.82). The two-night AHI ranged from 13 to 65. The average AHI change between pre-implant and post-implant (therapy off) was -0.3 ± 17 events/hour. The Sher 20 response rate between pre-implant and post-implant therapy off was 13%. By comparison, previously published mean AHI with therapy activated was approximately 10-15 events/hour, and Sher 20 response rates ranged between 65%-75%. ESS pre and post-implant (therapy off) were similar (12 ± 5 vs 11 ± 5, p=0.09), compared to ESS previously reported with HNS therapy activated (typically 6-7).

Conclusion
The STAR two-night baseline AHIs ranged between 13-65. While there were nightly differences in AHI in some patients, surgical implant of HNS with therapy off, did not result in meaningfully improvement in the AHI, Sher 20 response rate, or ESS.

Support (if any)
Inspire Medical Systems
0544 Occult Obstructive Sleep Apnea Increases Risk for Depression among Older Adult Medicare Beneficiaries
Authors: Albrecht Jennifer , Wickwire Emerson 
Published: May 2023

Abstract

Introduction
Depression and obstructive sleep apnea (OSA) are highly comorbid, and each is independently associated with worsened health outcomes and increased economic burden. This study aimed to determine the effect of occult OSA on incident depression among a national sample of Medicare beneficiaries. We hypothesized that relative to non-sleep disordered controls, older adults with occult OSA would demonstrate greater risk for incident depression during the year prior to OSA diagnosis.

Methods
Our data source was a random 5% sample of Medicare administrative claims data from 2006-2013. Obstructive sleep apnea, depression, and medical comorbidities were defined using International Classification of Disease, Version 9, Clinical Modification diagnostic codes during the twelve months prior to OSA diagnosis. Beneficiaries with history of depression prior to the beginning of follow-up (12 months before OSA diagnosis) were excluded. Non-sleep disordered controls were required to possess no evidence of sleep-related diagnosis, testing, or treatment during the study period. Log binomial regression was used to model risk for incident depression as a function of occult OSA. Inverse probability of treatment weights were used to balance covariates between exposure groups.

Results
The final sample included a total of 21,116 beneficiaries with occult OSA and 237,375 individuals without sleep disorders. In fully adjusted models, beneficiaries with OSA demonstrated significantly higher risk of depression during the year prior to OSA diagnosis (risk ratio 3.19; 95% confidence interval 3.00, 3.39).

Conclusion
In this national study of older adult Medicare beneficiaries, occult OSA was associated with three-fold risk of incident depression. Future research should 1) examine the disease burden including health and economic consequences, of comorbidity OSA and depression and 2) also seek to determine the effect of screening, assessing, and treating OSA on risk for depression.

Support (if any)
This research was supported by an investigator-initiated grant from the ResMed Foundation to the University of Maryland, Baltimore (PI: EMW).
0550 Positive Airway Pressure for Obstructive Sleep Apnea in Diastolic Heart Failure Patients Reduces Healthcare Resource Utilization
Authors: Kuniyoshi Fatima Sert , Cistulli Peter , Cole Kate , Malik Anita , Pépin Jean-Louis , Benjafield Adam , Somers Virend 
Published: May 2023

Abstract

Introduction
Although diastolic heart failure (HFpEF) patients frequently have comorbid obstructive sleep apnea (OSA), which has been associated with poor prognosis, the impact of positive airway pressure (PAP) therapy 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 HFpEF.

Methods
A national sample of administrative claims data linked to objective PAP therapy usage was used for this analysis. Eligible patients either had two healthcare encounters or one hospitalization with a diastolic 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
4,237 patients with OSA and comorbid HFpEF were included. With propensity score matching, 963 PAP adherent and 963 non-adherent patients remained. After 1 year of PAP therapy, adherent patients had fewer visits than non-adherent patients (1.16 visits per subject vs. 1.75, p &lt; 0.001), driven by a 57% reduction in hospitalizations and a 36% reduction in ER visits for adherent patients. Total HCRU costs were lower in adherent patients than in non-adherent patients ($12,732 vs. $15,610, p&lt; 0.01). Converting 1 patient from non-adherent to adherent would avoid 1.25 visits (either ER visit or hospitalization), with an NNT of 0.8.

Conclusion
HFpEF patients with OSA that are adherent to PAP therapy for 1 year have fewer hospitalizations and ER visits than patients that are not adherent. More importantly, HCRU costs were lower in adherent patients, highlighting the clinical and economic benefits of treating OSA with PAP therapy in HFpEF patients.

Support (if any)
Funding Source: ResMed
0554 Racial Disparities in Healthcare Resource Utilization among Older Adult Medicare Beneficiaries With Comorbid OSA and Depression
Authors: Wickwire Emerson , Albrecht Jennifer 
Published: May 2023

Abstract

Introduction
Depression and obstructive sleep apnea (OSA) are highly comorbid and independently associated with increased economic burden. Evidence suggests important racial disparities in diagnosis and treatment of each condition. This study sought to evaluate the economic burden of occult OSA among Black and White older adults with depression. We hypothesized that the impact of occult OSA on healthcare resource utilization would differ by race.

Methods
Data were derived from a 5% sample of Medicare administrative claims data. Inclusion criteria were age &gt;64 years, 12 months continuous enrollment prior to OSA diagnosis, depression, and Black or White race. Undiagnosed OSA and pre-existing depression were defined using ICD-10 codes during the 12 months prior OSA diagnosis. HCRU was defined as monthly counts of inpatient, outpatient, and emergency department (ED) visits in each of the 12 months before OSA diagnosis. The relationship between undiagnosed OSA and HCRU was modeled using negative binomial regression. Inverse probability of treatment (IPT) weighting was used to balance covariates between groups. Effect modification by race was evaluated using an interaction term; estimates were stratified by race.

Results
Of 39,192 beneficiaries with pre-existing depression, 4,353 suffered undiagnosed OSA (n=325 Black adults, 7.5%). Relative to White beneficiaries with undiagnosed OSA, Black beneficiaries with undiagnosed OSA were more likely to be female (76.6% vs. 68.6%, p=.002) and to suffer multimorbidity (&gt;7 comorbid conditions [71.7% vs 52.7%, p&lt;.001]). In IPT weighted models and relative to Black non-sleep disordered controls, Black beneficiaries with undiagnosed OSA had higher inpatient (RtR 1.89; 95% CI 1.33, 2.71), outpatient (RtR 1.38; 95% CI 1.04, 1.83) and ED (RtR 1.83; 95% CI 1.22, 2.75) utilization. Relative to White non-sleep disordered controls, White beneficiaries with undiagnosed OSA demonstrated higher inpatient (rate ratio (RtR) 1.51; 95% CI 1.38, 1.65)), outpatient (RtR 1.18; 95% CI 1.10, 1.26) and ED (RtR 1.45; 95% CI 1.34, 1.57) utilization. The interaction between race and undiagnosed OSA was significant in all models (p&lt;.001).

Conclusion
Among Medicare beneficiaries with pre-existing depression, comorbid undiagnosed OSA is associated with increased HCRU across multiple points of service. The strength of this association is greater among Black (vs White) beneficiaries.

Support (if any)
ResMed Foundation
0559 Solriamfetol Demonstrates Durable Cognitive Improvement in Adults with Obstructive Sleep Apnea and Excessive Daytime Sleepiness
Authors: Van Dongen Hans , Leary Eileen , Drake Christopher , Bogan Richard , Jaeger Judith , Rosenberg Russell , Streicher Caroline , Kwak Hannah , Bates Jay , Tabuteau Herriot 
Published: May 2023

Abstract

Introduction
Obstructive sleep apnea (OSA) is a common disorder characterized by repeated intermittent airway collapse—often a hypoxic event—resulting in disrupted sleep and excessive daytime sleepiness (EDS). Positive Airway Pressure (PAP) therapy reduces hypoxic events and mitigates sleep disruption, but EDS often persists. Cognitive impairment is a burdensome symptom in many patients with EDS associated with OSA, which leads to occupational and social dysfunction and degrades quality of life. Solriamfetol (Sunosi®) is approved to improve wakefulness in adults with EDS associated with OSA, but its effect on cognitive impairment was unknown. The SHARP study evaluated whether solriamfetol improves cognitive function in patients with OSA-associated EDS and impaired cognition, and the durability of cognitive effects across the day.

Methods
SHARP was a randomized, double-blind, placebo-controlled, crossover trial in 59 patients with OSA-associated EDS and concurrent cognitive impairment. All patients received solriamfetol (75mg for 3 days followed by 150mg/day) for 2 weeks, and placebo for 2 weeks, with treatment periods separated by a 1-week washout. The primary endpoint was change from baseline on the Coding subtest of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), which is equivalent to the Digit Symbol Substitution Test (DSST). Secondary endpoints measured durability of effect spanning an 8-hour period and Patient Global Impression of Severity (PGI-S).

Results
The study completion rate was 96.7%. Solriamfetol treatment improved performance on the DSST-RBANS compared to placebo (6.49 vs. 4.75, p=0.009), with an effect size (Cohen’s d) of 0.36. Solriamfetol also yielded improvements at post-dose timepoints throughout the day (solriamfetol-placebo difference): 2 hours (1.91, p=0.033), 4 hours (1.38, p=0.089; NS), 6 hours (2.33, p=0.004), 8 hours (1.58, p=0.022). Scores on the PGI-S improved with solriamfetol compared to placebo (-0.90 vs -0.61, p=0.034). The most common adverse events with solriamfetol treatment (incidence ≥3%) were nausea (6.9%) and anxiety (3.4%).

Conclusion
The adverse events profile and high completion rate suggest solriamfetol (150mg/day) was well tolerated. Moreover, solriamfetol improved cognition as measured by the DSST-RBANS, demonstrated durable effects over an 8-hour period, and reduced perceptions of symptom severity. Thus, in patients with OSA-associated EDS and impaired cognition, solriamfetol durably improved cognitive performance.

Support (if any)
Axsome Therapeutics Jazz Pharmaceuticals
0562 The characteristics of the older continuous positive airway pressure (CPAP) users in Japan: In comparison with the adult users
Authors: Kido Keisuke , Mihara Takenao , Wada Shin-ichi , Egawa Naohiro , Sugita Naoko , Hamano Toshiaki , Tachibana Naoko 
Published: May 2023

Abstract

Introduction
The characteristics of the older CPAP users have not been well studied, and accessibility to medical care and long-term follow up are the issues about their investigation of the older OSA patients. In this respect, Japan is in a unique position to look into reality of the situation, as virtually all the people have unlimited access to medical care and CPAP follow-up with one to three month interval is mandatory. Under this condition, the aim of this study is to reveal the characteristics of the older CPAP users compared to the adult users.

Methods
This is a retrospective study dealing with 340 obstructive sleep apnea patients who started CPAP therapy from May 2013 to Oct 2021 in our sleep laboratory. Two groups of CPAP users were extracted from these patients, older (n=44, with the age of 70 years or more, 75.8±4.4 years) and adult (n=26, with the age of 25-44 years old, 39.2±4.5 years) patients. We assessed the characteristics of demographic data, symptoms and comorbidity, diagnostic polysomnographic parameters, and CPAP adherence.

Results
The older CPAP users were leaner (BMI, older/adult, 24.9 [21.9-26.8]/31.3 [27.1-34.8], p&lt; 0.0001) and less sleepy (Epworth Sleepiness Scale, older/adult, 8.0 [5.0-13.0]/15.5 [8.8-20.2], p&lt; 0.0005). Apnea-hypopnea index (AHI) of two groups were not significantly different (older/adult, 38.6 [27.4-48.0]/49.5 [26.4-66.4]). Most of both older and adult patients continued to use CPAP more than one year (84.1 % and 92.3 %, respectively). CPAP adherence using more than one year in the older group was higher than that in the adult group (older/adult, 96.5 %/80.0 %).

Conclusion
Our study revealed that CPAP adherence in the older users was higher than that in the adult users, although the older CPAP users were leaner and less sleepy.

Support (if any)
0576 Characterization of Patients With Narcolepsy Treated vs Not Treated With Sodium Oxybate: A Propensity Score–Matched Cohort Study
Authors: Lipford Melissa , Asfahan Shahir , Singh Gajinder Pal , Moore J Layne , Tippmann-Peikert Maja , Kumar-M Praveen , Ip Wui , Awasthi Samir , Gudeman Jennifer , Krahn Lois 
Published: May 2023

Abstract

Introduction
Narcolepsy is a chronic sleep disorder with multiple comorbid conditions. Sodium oxybate (SXB) is strongly recommended for treatment of narcolepsy. This study used aggregate electronic health record (EHR) data to characterize demographic characteristics and comorbidities of patients with narcolepsy treated with or without SXB.

Methods
An EHR-based search identified first-time Mayo Clinic patients between 1975–2020. Patients had ≥1 narcolepsy-specific ICD-9/-10 code and ≥1 diagnostic mention of narcolepsy in clinical notes (natural-language-processing algorithm). Patients with narcolepsy treated with SXB were age/sex matched with a cohort without SXB treatment. Common comorbidities were identified using ICD-9/-10 codes and compared between cohorts (odds ratio [OR]).

Results
Of 4387 patients identified, 8% received SXB treatment (n=351; mean [IQR] age at first diagnosis code observed at Mayo Clinic, 32 [23.2-46.1] y; 65.5% female; 92.3% white); 4036 patients had no SXB treatment (mean [IQR] age at first diagnosis code observed at Mayo Clinic, 44.8 [29.8-59.0] y; 58.0% female; 88.9% white). The 10 most commonly reported comorbidities (overall population) were insomnia (46.6%), fatigue (46.3%), depression (42.2%), hypertension (36.2%), hyperlipidemia (34.2%), obstructive sleep apnea (32.3%), diabetes mellitus (31.3%), arrhythmia (27.3%), idiopathic hypersomnia (IH; 26.8%), and coronary artery disease (17.6%). A cohort of 351 patients without SXB were age/sex matched to patients with SXB for comparison of comorbidities. In the unadjusted analysis, P values were significant for differences between cohorts (OR [95% CI] SXB vs no SXB) for fatigue (0.72 [0.54-0.97]; P&lt; 0.05; adjusted P&gt;0.9) and IH (0.60 [0.43-0.84]; P&lt; 0.01; adjusted P=0.29). After P value adjustment (Bonferroni correction), there were no significant differences between these cohorts in ORs for any comorbidity. The matched cohorts, which were younger than the overall population, had numerically lower rates of these diagnoses vs the overall population, except fatigue and IH in patients without SXB and depression in patients with SXB.

Conclusion
Among age-/gender-matched cohorts of patients with/ without SXB, there were no significant differences in comorbidities. Prevalence of comorbid IH/narcolepsy diagnoses highlight the diagnostic challenge in differentiating IH from narcolepsy type 2. SXB is highly effective but used by &lt; 1:10 patients with narcolepsy in the Mayo Clinic health system.

Support (if any)
Avadel Pharmaceuticals
0577 Clinically Meaningful Improvements With Pitolisant in Adults With Narcolepsy: Pooled Analysis of Randomized Clinical Trials
Authors: Wells Audrey , Albers David , Doliba Markiyan , Zarycranski Donna , Schwartz Jean-Charles , Dayno Jeffrey 
Published: May 2023

Abstract

Introduction
Narcolepsy is characterized by symptoms indicative of sleep–wake dysregulation, notably excessive daytime sleepiness (EDS) and cataplexy. In 2021, the American Academy of Sleep Medicine (AASM) updated its clinical practice guidelines on the treatment of central disorders of hypersomnolence. The AASM identified clinical significance thresholds (CSTs) of a 2-point reduction in Epworth Sleepiness Scale (ESS) score and a 25% reduction in the frequency of cataplexy, amongst others, to compare posttreatment effects between intervention and placebo. This post hoc analysis evaluates the efficacy of pitolisant in the treatment of patients with narcolepsy using these updated CSTs.

Methods
Data were pooled from 2 randomized, placebo-controlled, 7- and 8-week studies (HARMONY-1, HARMONY-CTP) of pitolisant in adults with narcolepsy. Pitolisant was individually titrated over a 3-week period (maximum potential dose, 35.6 mg/day), and the dose remained stable thereafter. The analysis population for EDS included all patients who received pitolisant or placebo (ESS score ≥12 required for study inclusion). The analysis population for cataplexy included treated patients who experienced ≥3 attacks per week at baseline. The end-of-treatment value for the ESS was the score at the last study visit (last observation carried forward [LOCF]). The cataplexy endpoint was the weekly rate of cataplexy (WRC) during the stable dose period (LOCF).

Results
Data from 166 patients for EDS (pitolisant, n=85; placebo, n=81) and 122 patients for cataplexy (pitolisant, n=64; placebo, n=58) were analyzed. Mean (SD) baseline ESS score was 17.6 (3.0) in the pitolisant group and 17.9 (3.1) in the placebo group. Mean (SD) baseline WRC was 12.4 (10.7) and 9.9 (9.0), respectively. At the end of treatment, ESS score reduction of ≥2 points was observed in a significantly greater percentage of patients in the pitolisant group (72.9%) as compared with the placebo group (45.7%; P&lt; 0.001). The percentage of patients with a reduction in WRC of ≥25% was significantly greater with pitolisant (78.1%) versus placebo (34.5%, P&lt; 0.001).

Conclusion
Pitolisant provides statistically significant and clinically meaningful reductions in EDS and cataplexy in patients with narcolepsy, based upon the CSTs associated with the updated AASM clinical practice guidelines.

Support (if any)
Bioprojet Pharma and Harmony Biosciences, LLC.
0578 Clinician and Patient Global Impression in a Phase 2 Study of Mazindol (NLS-1021) in Adults with Narcolepsy Type 1 and Type 2
Authors: Bogan Richard , Stern Thomas , Corser Bruce , Franco Jennifer , Konofal Eric , Apostol George , Morse Anne , Kushida Clete , Thorpy Michael , Rosenberg Russell 
Published: May 2023

Abstract

Introduction
Mazindol is the first partial orexin 2 receptor agonist and triple monoamine reuptake inhibitor in development for the treatment of narcolepsy. Clinician and Patient Global Impression (CGI and PGI, respectively) for cataplexy and excessive daytime sleepiness were assessed as secondary endpoints in the phase 2 (POLARIS, NLS-1021) multicenter study of mazindol ER in adult participants with narcolepsy type 1 (NT1) or type 2 (NT2) (ClinicalTrials.gov Identifier: NCT04923594).

Methods
Adults diagnosed with NT1 or NT2 who were washed out of narcolepsy medications at baseline were included into the study. Patients were treated with mazindol ER (NLS-2) at once-daily 2 mg for one week and once-daily 3 mg thereafter or matching placebo (PBO) on a 1:1 ratio. Throughout the study, CGI Severity (CGI-S) and PGI Severity (PGI-S) for cataplexy severity and excessive daytime sleepiness, respectively, were assessed and compared with scores at baseline. Both scales have five levels of severity: “None”, “Mild”, “Moderate”, “Severe”, or “Very Severe.”

Results
Sixty-seven participants were randomized (NT1 33.3% in NLS-2 group; 35.3% in PBO). At baseline, the mean CGI-S – Cataplexy was approximately 3.7 and CGI-S – Sleepiness approximately 3.4. Despite the small sample size, at the end of the double-blind (DB) period, the NLS-2 group demonstrated clinically and statistically significant improvements vs. PBO in both CGI-S – Sleepiness (d = –0.7, p = 0.016) and CGI-S – Cataplexy (d = –0.8, p = 0.020). At baseline, the mean PGI-S – Cataplexy was approximately 3.2 and PGI-S – Sleepiness approximately 3.7. At the end of the DB period, the NLS-2 group demonstrated clinically and statistically significant improvements vs. PBO in both PGI-S – Sleepiness (d = –0.8, p = 0.007) and PGI-S – Cataplexy (d = –0.8, p = 0.023).

Conclusion
Mazindol ER resulted in significant improvements of cataplexy severity and sleepiness in both conditions as rated by both clinicians and participants. These secondary outcome results support the efficacy of mazindol ER on cataplexy attacks, in NT1 participants, and on sleepiness, in NT1 as well as in NT2 participants.

Support (if any)
NLS Pharmaceutics