bluuebunny/crossref_metadata_2025 huggingface dataset:
0533 Healthcare Utilization by Patients with Obstructive Sleep Apnea and Excessive Daytime Sleepiness After Airway Therapy in the UK
Authors: Abeynayake Iresha , O'Donohoe Peadar , Floam Samantha , Romero-Cruz Pamela , Andiappan Mano , McCormack Mark , Parks Gregory
Published: May 2023

Introduction

Obstructive Sleep Apnea (OSA) is a chronic condition characterized by repetitive episodes of upper airway collapse during sleep. Despite standard treatment with continuous positive airway pressure (CPAP), some patients continue to experience residual excessive daytime sleepiness (rEDS). Pharmacotherapy use for rEDS is low in Europe and some wake-promoting agents are no longer allowed as treatments by the European Medicines Agency. The objective of this study was to characterize the patient demographics, comorbidities, medications, and healthcare resource utilization (HCRU) in a population of OSA patients with and without rEDS after CPAP initiation.

Methods

The retrospective observational cohort study used the Clinical Practice Research Datalink (CPRD) AURUM, a primary care database, linked at the patient level to the Hospital Episode Statistics (HES) database, which covers secondary care for all of England. The population included 10,746 adult OSA patients with a first record of CPAP treatment during the eligibility period (Jan 1, 2009-Mar 21, 2018). rEDS patients were identified 6 months after initiating CPAP treatment.

Results

Among all eligible OSA patients in the AURUM database, 596 (5.6%) had rEDS; 80.5% of rEDS patients were identified using recorded diagnosis code of daytime fatigue, and 21.7% using ESS score ≥11 (13 patients had both measures). A greater percentage of patients had a history of psychiatric (21.5%; p< 0.0001), gastrointestinal (7.7%; p< 0.0001), and neurodegenerative (13.6%; p=0.003) disorders in the rEDS group, compared with the non-rEDS group, while the prevalence of obesity, cardiovascular, and sleep disorders did not significantly differ between groups. Across all patients, rates of prescription for stimulants or modafinil were low during the 12 months prior to CPAP initiation. Patients with rEDS had significantly higher HCRU compared to non-rEDS patients in the first and second years after CPAP initiation.

Conclusion

Despite low rates of rEDS identified in this study, the clinical needs of patients with rEDS are significant, as evidenced by the volume of HCRU, low use of pharmacotherapy, and high comorbidity rates, highlighting the need to improve patient care in rEDS.

Support (if any)

Axsome Therapeutics and Jazz Pharmaceuticals
0534 How objective sleep quality with Odds Ratio Product differs by diagnosis of COMISA, OSA, and insomnia
Authors: Tomson Heather , Bender Amy , Lambing Kari , Guadagni Veronica
Published: May 2023

Introduction

Recent research has highlighted differences in sleep quality for comorbid insomnia and obstructive sleep apnea (COMISA). We investigated how COMISA affects objective sleep quality measured with odds ratio product (ORP) compared to individuals without insomnia or moderate to severe OSA.

Methods

410 participants (age 46.4±12.3; 174 females) recorded their sleep with in-home PSG using the Cerebra Sleep System and completed questionnaires. Sleep quality was measured using ORP derived from micro-analyzing frontal EEG channels. On the questionnaires, participants reported whether they experienced insomnia symptoms at least three times a week. Participants were classified as having no diagnosis if their RDI on the home PSG was < 15 and no insomnia symptoms. They were classified as insomnia only if they reported at least one insomnia symptom with an RDI < 15. They were classified as OSA only if they had an RDI ≥15 and reported no insomnia symptoms. Finally, they were classified as COMISA if they had an RDI ≥15 and reported at least one insomnia symptom. All analyses controlled for age and were corrected for multiple comparisons.

Results

113(27.6%) patients were classified as having no diagnosis, 109(26.6%) as insomnia only, 83(20.2%) as OSA only, and 105(25.6%) as COMISA. There was a significant effect of diagnosis on ORPNREM (F3,405= 6.042, p<.001) and ORPTRT (F3,405= 3.799, p= 0.010). Participants with no diagnosis had lower ORPNREM than patients with OSA only (p= 0.039) and patients with COMISA (p<.001) and had lower ORPTRT than COMISA (p= 0.009). OSA severity based on the AHI was the only significant predictor of ORPNREM (p <.001, β= 0.321). Both AHI (p <.001, β=0.176) and number of insomnia symptoms (p=0.002, β=0.141) were significant predictors of ORPTRT.

Conclusion

Participants with no diagnosis had the lowest ORP indicative of better sleep quality than participants with evidence of sleep disorders. Having COMISA may have greater impacts on sleep quality than insomnia symptoms alone. OSA severity was the only predictor of poor sleep quality when looking at ORPNREM. Yet both OSA severity and insomnia symptoms were associated with higher ORPTRT indicating that individuals with COMISA may show alterations of sleep quality in different states throughout the night.

Support (if any)
0536 Impact of Positive Airway Pressure Therapy on Clinical Outcomes in Older Veterans with Comorbid COPD and OSA: An Update
Authors: Greig Danny , Rastogi Ruchi , Bansal Jaskiran , Mishra Poonam , Ahmed Abdullahi , Zhao Lili , Mcconnell Andrew , Kushida Clete , Axelrod Bradley , Shamim-Uzzaman Q Afifa , Chowdhuri Susmita
Published: May 2023

Introduction

Cognitive impairment in older Veterans is an independent predictor of subsequent mortality and disability. Pilot data indicate that patients with OSA-COPD Overlap Syndrome (OVS) may have reduced sleep quality, cognitive function and quality of life (QoL). However, there are no prior systematic studies evaluating treatment paradigms in patients with OVS. Our ongoing clinical trial is investigating whether positive airway pressure (PAP) therapy alleviates sleep disturbances, sleepiness, and improves cognitive function and QoL in older adults with OVS.

Methods

The design is a prospective parallel group randomized controlled trial in Veterans 60 years and older, with moderate-to-severe OSA with concomitant COPD (OVS). 225 eligible participants will be randomized to two treatment groups (PAP and conservative care) in 2:1 ratio for a duration of 6 months. Participants on the conservative care arm are required to follow good sleep habits and sleep hygiene, and on the PAP arm, in addition, are required to be adherent to PAP treatment (CPAP or Bilevel PAP, as required). Sleep questionnaires are administered to evaluate sleepiness, sleep quality, and general and disease specific QoL. Cognitive function is evaluated using Trail Making Test Part A and B, Paced Auditory Serial Addition Test, Stroop Task, Digit Coding, Hopkins Verbal Learning Test-R, Weschler Abbreviated Scale Intelligence II, Weschler Memory Scale IV, and Psychomotor Vigilance Test, respectively. All tests are administered at baseline visit, 3 months, and 6 months.

Results

In year-2 of the study, we have screened 7878 Veterans, enrolled 137 participants, randomized 34 participants (31 males, 3 females; age: 70.7±6.6 years, BMI: 29.6±6.7 kg/m2, AHI: 47±22 events/hr, spirometry FEV1: 60.8±11.7% predicted, arterial blood gas (n=22) pCO2:41.2 ±3.6 mmHg, ESS: 1.9 ±2.4); 15 have completed the study per the protocol. Analysis of data will be completed at the end of the RCT.

Conclusion

Our research seeks to systematically study the effects of treating a novel target (OVS) to maximize daytime function and QoL, while also providing a framework for early treatment of mild cognitive impairment in vulnerable older Veterans.

Support (if any)

VHA RR&D Merit Award # 1I01RX003124-01
0537 Incident Hypertension Prediction in Obstructive Sleep Apnea using Machine Learning
Authors: Milani Omid Halimi , Nguyen Tu , Parekh Ankit , Cetin Ahmet Enis , Prasad Bharati
Published: May 2023

Introduction

Obstructive sleep apnea (OSA) is associated with hypertension due to intermittent hypoxia and sleep fragmentation. Due to the complex pathogenesis of hypertension, it is difficult to predict incident hypertension associated with OSA. A Machine Learning (ML) model to predict incident hypertension identified up to five years after the diagnosis of OSA by polysomnography developed.

Methods

Polysomnography provides time-series data on multiple physiological signals. We used the sleep heart health study (SHHS) cohort, where 4,797 participants had OSA. After excluding participants with pre-existing hypertension at baseline, the sample size was 2,652. 1,814 participants with follow-up data at 5 years were included (911/1,814, 50% with incident hypertension). In addition to clinical data (i.e. age and race), features extracted from polysomnography (heart rate variability, HRV calculated based on the electrocardiography R-R interval), electroencephalography delta power, statistical information (i.e., mean and standard deviation of signals), and heart rate periodicity functions fed to support vector machine (SVM) ML model to train and validate. The polysomnography features were calculated over the 30-second epochs identified based on respiratory events and EEG arousal and respiratory events annotation, and their corresponding parts in other signals based on sampling frequency. Technical artifacts in oxygen saturation and ECG were reconstructed with the interpolation method and removed from the signal respectively. The SVM is a robust ML method trained in an iterative fashion to find the global optimum. In comparison to the Deep Neural Network (DNN) approaches, SVMs results are interpretable. Each polysomnography signal and its corresponding features were trained on a separate SVM, followed by a fusion of the SVM results. The final results were fused by voting of individual SVM results.

Results

The SVM ML model thus far has achieved a test accuracy (area under the curve, AUC) of 66.06%, sensitivity 63.21%, and specificity 68.9%.

Conclusion

This proof-of-concept study suggests that supervised ML models, such as the SVM, may be useful in predicting incident hypertension associated with OSA. Further research is required regarding optimal input features to boost the accuracy, followed by external validation of the model in additional OSA cohorts.

Support (if any)

Research support 1R56HL157182, NIH/NHLBI
0541 Obstructive Sleep Apnea Following Vagus Nerve Stimulator Implantation: A Meta-Analysis
Authors: Saleem Matthew , Santhumayor Brandon , Hasan Eusha , Kolesnik Michael , Bernbaum Melissa
Published: May 2023

Introduction

Vagus nerve stimulation (VNS) treatment for patients with intractable epilepsy has been shown to effectively lower seizure frequency and improve quality of life. However, due to stimulation of the vagus nerve, alterations in both central regulation of breathing and laryngeal muscle stimulation can precipitate obstructive sleep apnea (OSA). While there have been case reports describing OSA following VNS implantation, there has yet to be a detailed evaluation of this complication in a large cohort of VNS patients. The objective of this meta-analysis was to determine OSA rates in patients following VNS implantation.

Methods

English full-text articles were searched for on Pubmed, Scopus, and Embase databases. Articles had to follow patients before and after VNS implantation; report apnea-hypopnea index (AHI), respiratory disturbance index (RDI), or OSA rates following VNS implantation; be from a clinical trial, cohort, or case-control study. Two reviewers reviewed articles and a third settled disagreements. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies were used. Following Freeman-Tukey transformation, the generic inverse variance method with random effects model was used for meta-analysis.

Results

Ten studies, seven retrospective and three prospective, representing a cohort of 306 patients were included in this study. Pooled OSA rates following VNS implantation were 27.3%, 95% CI: 15.1 - 41.5%. Subgroup analysis found no difference in rates between studies of pediatric populations (22.1%, 95% CI: 8.2 - 40.5%) and adult populations (31.9%, 95% CI: 18.9 - 47.5%) following VNS implantation (P = 0.39). There was significant heterogeneity in pooled analysis (P < 0.00001, I2 = 100%), but no inter-subgroup heterogeneity (I2 = 0%).

Conclusion

Obstructive sleep apnea is a common adverse effect following VNS treatment and patients should be monitored following implantation. There are no differences in OSA rates between pediatric and adult populations. Routine screening for OSA following VNS implantation may be a reasonable choice.

Support (if any)

No institutional or NIH funding was received for this project
0545 Optimizing Access to Oral Appliances for OSA: Decrease Cost and Increase Availability with 3D Printing
Authors: Russo Steven , Hardin Kimberly
Published: May 2023

Introduction

Mandibular advancement devices (MAD) for obstructive sleep apnea have traditionally been a prohibitive therapy for a large number of patients due to high out-of-pocket expense and access to dentistry. This study examined if an increasingly more accessible and user-friendly technology, 3D printing, may provide a cost-effective in-office workflow to increase access to MAD use.

Methods

Available pricing data was sourced via PubMed articles searching keywords “oral appliance”, “sleep apnea”, “mad” and “cost”. Additional price point data was compiled from publicly available information from the largest dental insurance provider in the United States, Delta Dental. Computer Aided Design (CAD) software Fusion360 was used to prototype a MAD and Stereolithography (SLA) printing using FormLab’s 3B+ printer was performed by a University-run 3D printing lab.

Results

Traditional cost per MAD ranges from 400USD – 2,450USD with a mean of 933USD (based on the only available 1997 pricing data). The total cost of the one-off MAD used in this study was 150USD (consumable cost of 2.66USD, labor cost of 147.34USD). This excluded the one-time 3D printer cost of 3,750USD. At 1 device printed per day over 1 year, total cost per printed device would be estimated at $22, which is 5% of the traditional cost of MAD. Total print time is estimated at 54 minutes, post processing time is estimated at 25 minutes, with a total MAD delivery to patient time of 1.3 hours.

Conclusion

Point-of-care 3D printed oral appliances are a feasible and inexpensive workflow to expand the use of MADs in the treatment of mild to moderate sleep apnea. Multiple barriers remain in integrating this workflow into patient care, including integration with dentistry.

Support (if any)
0548 Position-dependent obstructive sleep apnea and the cardiovascular risks
Authors: Chow Christine , Kang Hyojung , Logan Jeongok , Sohn Min-Woong , Bonner Heather , Lobo Jennifer , Kwon Younghoon
Published: May 2023

Introduction

Position dependent obstructive sleep apnea (PdOSA) is highly prevalent, but the implication of PdOSA in cardiovascular (CV) outcomes has not been studied. We hypothesized that PdOSA is associated with lower risk of future CV events than those without PdOSA.

Methods

We included patients who underwent diagnostic polysomnography (PSG) at a single academic center. The study included patients with ≥2 hours of total sleep time, 30 minutes in both supine and non-supine sleep, and OSA (apnea hypopnea index [AHI]≥5/hr). We defined PdOSA as either POSA (overall AHI≥5/hr accompanied by supine AHI (sAHI) at least twice as high as non-supine AHI (ns-AHI)), or ePOSA (POSA criteria + ns-AHI < 5/hr (i.e., normalized)). Blood pressure (BP) was derived by averaging multiple measures of clinic BP within 1 year of PSG. All patients were followed up to 11 years to identify incident CV events (including acute coronary syndrome, stroke, and new heart failure). We examined the association of PdOSA with CV events with a logistic regression, adjusting for age, sex, race, BMI, systolic BP, and OSA severity (mild [AHI 5-15] vs. moderate to severe [≥15]).

Results

A total of 1750 patients (mean age: 54 years, female 60%) were included. POSA and ePOSA were present in 47% and 23% of the cohort. Patients with either POSA or ePOSA were less obese and had less severe OSA compared with those without POSA and ePOSA. Patients with ePOSA had lower BP (systolic BP 128.8 vs 131.2 mmHg, p=0.003) than those without ePOSA. Over a median 8.3 years of follow-up, a total of 340 CV events occurred. In multivariable analysis, both POSA and ePOSA were associated with lower odds of future CV events (OR 0.8, 95% CI [0.64-0.99], p=0.044; OR 0.69 [0.52-0.89], p=0.0061, respectively). Analysis stratified by OSA severity showed that the ePOSA association was present only in those with mild OSA (OR 0.67 [0.48-0.94], p=0.021).

Conclusion

Among patients with OSA, PdOSA is associated with more favorable CV outcomes than those without PdOSA. The benefit appears to be limited to those with mild OSA. Future studies should compare the CV risks between PdOSA patients and those without OSA.

Support (if any)
0552 Predictive Characteristics of Run-In Period Adherence in a Randomized Controlled Trial
Authors: Obeid Carla , Puri Reena , Aylor Joan , Wang Lu , Mehra Reena
Published: May 2023

Introduction

The run-in period has been used in randomized controlled trials in obstructive sleep apnea (OSA) to assess continuous positive airway pressure (CPAP) adherence. We hypothesize that there are differences in participant characteristics and PAP adherence between those excluded after the run-in period and those included in the final analytic sample of the Sleep Apnea Stress Study (SASS, NCT00607893), a trial designed to examine effect of PAP treatment on intermediate cardiovascular outcomes.

Methods

The SASS trial was designed to include a 2-week run-in period with a 1-month wash-out period. Patients with CPAP adherence >4 hours of CPAP use for 70% of run-in period nights were randomized. Demographic factors were compared among groups using analysis of variance (ANOVA) or Kruskal-Wallis test in continuous variables, Pearson’s chi-square test or Fisher’s exact test was used for categorical variables. Bonferroni correction was applied for pairwise comparisons. SAS version 9.4 (The SAS Institute Cary, NC) was used to perform all analyses.

Results

Fifty-nine participants(30.8%) who did not meet PAP adherence threshold were excluded after run-in period and compared to Sham and CPAP treatment group(n=74 in each group). Results are presented as excluded vs sham treatment vs CPAP treatment. Participants excluded after the run-in period were more likely to be female than those who proceeded to randomization: 66% vs. 47% vs. 45%,p=0.031 and of Black race:73% vs. 42% vs. 47%, p=0.002. Participants excluded after the run-in period and those non-adherent to treatment in sham and CPAP were younger than adherent participants: excluded: 48.9±12.0, sham non-adherent 49.7±12.3, CPAP non-adherent 47.7 ± 13.2, sham adherent 58.3±9.3, CPAP non-adherent 54.3 ± 9.4, p=0.014. In the run-in period, participants who were excluded had the median of number of days using the device 12 (IQR 7-15), mean of average daily use 2.8±2.1 hours and median percent of days with 4+ hours use 18.2% (IQR 0-57.1%).

Conclusion

We identify that age and race are predictors of run-in period non-adherence to PAP therapy underscoring the need to develop pre-randomization PAP adherence optimization strategies specific to these subgroups to ensure representation in the trial.

Support (if any)

This work was supported by NIH HL079114-02.
0553 Prevalence of Insomnia and Anxiety in a National Sample of Patients with Obstructive Sleep Apnea and Depression
Authors: Cole Kate , Dexter R Benjamin , Pépin Jean-Louis , Sterling Kimberly , Wickwire Emerson
Published: May 2023

Introduction

Insomnia and anxiety are highly comorbid both with depression and with obstructive sleep apnea (OSA). This retrospective study sought to characterize patients with these conditions among a national sample of individuals with depression and comorbid OSA.

Methods

A national sample of administrative claims data of OSA patients was used for this analysis. Included patients either had two healthcare encounters or one hospitalization with a depression ICD-10 diagnosis code the year prior to OSA diagnosis and before initiation on positive airway pressure (PAP) therapy for treatment of OSA. Anxiety, insomnia, and other comorbidities were identified by the presence of at least one ICD-10 code associated with healthcare encounters in the year prior to starting PAP therapy. Age, sex, and insurance coverage were characterized at the time of the first OSA diagnostic sleep test. Healthcare resource utilization was assessed for the year prior to starting PAP therapy.

Results

36,668 patients with depression and comorbid OSA were included. 56% had comorbid anxiety, 28% had comorbid insomnia, and 35% had neither anxiety nor insomnia. Compared to those without anxiety or insomnia, patients with anxiety or insomnia were more commonly female (64% vs 57%) and had a higher prevalence of asthma (25% vs 20%), psychotic (14% vs 7%) and other mood disorders (24% vs. 14%), fibromyalgia (11% vs 7%) and GERD (43% vs 33%). Relative to individuals with insomnia or anxiety, patients without insomnia or anxiety experienced fewer ER visits, all-cause hospitalizations, depression-related hospitalizations, specialist visits, and self-harm events in the year prior to PAP initiation. Relative to patients with comorbid insomnia, those with comorbid anxiety demonstrated slightly higher healthcare resource use in the year prior to PAP initiation.

Conclusion

Anxiety and insomnia are prevalent comorbidities in patients with depression and obstructive sleep apnea, with more than half of patients suffering comorbid anxiety and a quarter of patients having comorbid insomnia. Future research should examine comprehensive patient care strategies that can be used in patients with comorbid anxiety or insomnia to encourage healthy sleep behaviors and successful acclimation to OSA treatment.

Support (if any)

ResMed
0555 Sex and Age Differences in Rapid Eye Movement Related Obstructive Sleep Apnea
Authors: Block Lucy , Suarez-Rivas Hailie , Hong Xinyi , Buckley Ashura
Published: May 2023

Introduction

Rapid Eye Movement (REM) related Obstructive Sleep Apnea (OSA) is a subcategory of OSA in which apneas or hypopneas occur predominantly or exclusively during REM and may be more prevalent in women and children. There is no consensus on the definition. Here, we examine interactions of age and sex on diagnosis per definition.

Methods

Patients who underwent a PSG at the Sleep Service at NIH in a 24- month period were included. Four REM-OSA definitions used most in the literature represented the diagnostic criteria.

Results

139 total participants (ages 1.5-76 y, 58 female) were evaluated. Twenty-eight men (20%) and eighteen women (13%) met criteria for at least 1 definition. Twenty participants (1.5-76 years) met definition one (9 female), 19 met definition two (9 female), 19 met definition three (9 female), and 36 met definition four (15 female). Fifteen of fifty-six (27%) pediatric patients (8 female) met criteria by at least one definition. Two female pediatric participants met definitions one, two and three, and all 15 pediatric participants met definition four. The average total AHI was 5.93 for women and 7.78 for men, while the average REM AHI was 17.96 (5.6-47.1) for women and 17.14 (5.3-51.7) for men. Twenty-six (18 female) REM-OSA patients had a total AHI of less than 5. For pediatric patients the average total AHI was 3.56 for girls and 2.73 for boys, and the average REM AHI was 9.41 for girls and 8.29 for boys.

Conclusion

The prevalence of REM-predominant OSA is difficult to determine as there are multiple definitions in use. REM-predominant OSA has been associated with hypertension, poor glycemic control, and mood disturbance and may be underdiagnosed due to current guidelines. Current definitions of mild, moderate and severe apnea are based on total AHI over the course of the sleep period. In our study, more than half of participants with REM-OSA by any definition had a total AHI of less than 5, despite the high average REM AHI for both sexes. These patients would not have met criteria for a diagnosis of OSA which has clear treatment implications.

Support (if any)

National Institutes of Health Intramural Research Program
0556 Simultaneous comparison of unedited and manually edited HSAT with level 1 PSG in persons with hospitalized TBI
Authors: Le Loan , Schwartz Daniel J , Nakase-Richardson Risa , Almeida Emily J , Anderson William , Patel Kevin , Sudolcan Benjamin , Nallu Sagarika
Published: May 2023

Introduction

Previous studies have shown automatic scoring of portable level 3 sleep study provides similar findings when compared to polysomnography (PSG), establishing home sleep apnea tests (HSAT) as an adequate screening tool for OSA. Accuracy of level 3 studies with Nox T3 portable sleep studies (Noxturna Inc., Atlanta GA) may improve with manual editing to include total sleep time (TST). No other studies have compared unedited versus manually edited HSAT with level 1 in-lab PSG performed simultaneously. This study evaluates if added manual editing optimizes the diagnostic accuracy of HSAT in classifying the severity of OSA, using both AASM and CMS criteria.

Methods

Secondary analysis of six-center (n=206) sleep apnea diagnostic comparative effectiveness trial. Participants underwent simultaneous administration of level 1 PSG (Philips Alice 6 LDx Diagnostic Sleep system) and Nox T3 portable sleep study with centralized scoring using AASM and CMS criteria. All HSAT were autoscored and then edited by the registered polysomnographic technician. Editing entailed establishing start and stop recording times based on accompanying actigraphy data (reduction in movement) in the portable device and elimination of recording artifact.

Results

Using AASM criteria, poor sensitivity OSA (AHI≥5) was observed using unedited vs PSG (p=.01) compared to manually edited HSAT vs. PSG (p=.06). No statistically significant difference was observed using AHI≥15 or via categorization across four levels of OSA (none, mild, moderate, or severe). In contrast, CMS criteria comparisons to PSG showed poor specificity of OSA (AHI≥5) for unedited (p=.003) compared to edited (p=.372) HSAT studies. As expected, total sleep time was overestimated using T3 actigraphy devices compared to the criterion standard across both edited and unedited studies (p=.001, .001 respectively).

Conclusion

Improvements in sensitivity and specificity of OSA were noted using edited versus unedited T3 HSAT when compared to Level 1 PSG using both AASM and CMS criteria. Results support need for manualized editing of HSAT in persons with hospitalized TBI.

Support (if any)

PCORI (CER-1511-33005), GDHS (W91YTZ-13-C-0015)
0560 Solriamfetol for Excessive Sleepiness in Narcolepsy and Obstructive Sleep Apnea: Effect Sizes and Numbers Needed to Treat or Harm
Authors: Chepke Craig , Cutler Andrew , Floam Samantha , Parks Gregory , Rosenberg Russell
Published: May 2023

Introduction

Solriamfetol (Sunosi®), a dopamine/norepinephrine reuptake inhibitor that has been shown to activate TAAR1, is approved (US and EU) to treat excessive daytime sleepiness (EDS) in adults with narcolepsy (75-150mg/day) or obstructive sleep apnea (OSA) (37.5-150mg/day). Effect size, number needed to treat (NNT) and number needed to harm (NNH) are statistical representations of efficacy and tolerability that clinicians may find helpful in guiding treatment decisions. This analysis characterized these statistical parameters from two registrational studies.

Methods

We conducted a post-hoc analysis of data from two phase 3 studies in adults with excessive daytime sleepiness associated with narcolepsy (TONES 2) or OSA (TONES 3). Effect size compared to placebo, NNT, and NNH were calculated based on previously published endpoints, post-hoc analyses, and adverse events.

Results

On the Maintenance of Wakefulness Test, effect size compared to placebo (Cohen’s d) was 0.29, 0.82, and 1.13 for 75mg, 150mg, and 300mg doses of solriamfetol in TONES 2 and 0.46, 0.89, 1.08, and 1.28 for 37.5mg, 75mg, 150mg, and 300mg in TONES 3. On the Epworth Sleepiness Scale (ESS), d was 0.47, 0.80, and 1.02 for 75mg, 150mg, and 300mg in TONES 2, and 0.42, 0.37, 0.99, and 1.04 for 37.5mg, 75mg, 150mg, and 300mg doses in TONES 3. NNT for patients achieving an ESS ≤10 was 7, 5, and 3 for 75mg, 150mg, and 300mg doses in TONES 2 and 8, 6, 4, and 3 for 37.5mg, 75mg, 150mg, and 300mg doses in TONES 3. On the Patient Global Impression of Change (PGIc), NNT was 4, 3, and 3 for 75mg,150mg, and 300mg doses in TONES 2 and 16, 5, 3, and 3 for 37.5, 75mg, 150mg, and 300mg in TONES 3. Similar NNT were found for the Clinician Global Impression of Change as for the PGIc. In both TONES 2 and TONES 3, NNH pooled across doses for adverse events occurring in ≥5% of patients and greater than placebo were all >10, with the exception of headache in TONES 2 (NNH=6).

Conclusion

This post-hoc analysis demonstrates favorable effect size, NNT, and NNH values for solriamfetol in the treatment of EDS associated with narcolepsy and OSA.

Support (if any)

Axsome Therapeutics
0561 Solriamfetol Real World Experience Study: Safety, Efficacy, and Follow-Up for Patients with Obstructive Sleep Apnea in Germany
Authors: Winter Yaroslav , Mayer Geert , Kotterba Sylvia , Benes Heike , Burghaus Lothar , Parks Gregory , Abeynayake Iresha , Romero-Cruz Pamela , Floam Samantha , Kwak Hannah , Kallweit Ulf
Published: May 2023

Introduction

Excessive daytime sleepiness (EDS) is a symptom of Obstructive Sleep Apnea (OSA) that can persist despite primary airway therapy and can be managed with wake-promoting agents. Solriamfetol (Sunosi®) is a wake-promoting agent approved to treat EDS associated with OSA (37.5–150 mg/day). This real-world study characterizes dosing/titration strategies among European physicians initiating solriamfetol and patient outcomes following initiation.

Methods

This is an ongoing retrospective chart review conducted by physicians in Germany and France. Data are reported from 52 German patients with OSA. Eligible patients (≥18 years old, diagnosed with EDS due to OSA, reached a stable solriamfetol dose, and completed ≥6 weeks of treatment) were classified into 1 of 3 groups based on solriamfetol initiation strategy: changeover (switched/switching from existing EDS medication[s]), add-on (added/adding to current EDS medication[s]), or new-to-therapy (no current/previous EDS medication).

Results

Patients’ mean±SD age was 50.0±13.1 years; 65% were male. All patients used primary airway therapy. Obesity was the most common comorbidity (56%). New-to-therapy was the most common initiation strategy (n=39), then add-on (n=9), and changeover (n=4). The most common starting doses of solriamfetol were 37.5 (n=34; 65%) and 75 mg/day (n=17; 33%). Solriamfetol was titrated in 30 patients (58%); the majority were titrated within 7 days. Mean±SD Epworth Sleepiness Scale (ESS) score was 15.5±3.2 (n=52) at initiation and 10.7±3.7 at follow-up (n=48), with a mean decrease of 5.0± 3.2 points. Across subgroups, mean ESS scores at initiation and follow-up ranged from 15.2–16.8 and 10.3-11.6, with mean decreases from 4.5–6.5 points. Improvements in EDS after solriamfetol initiation were reported for most patients (patient-reported, 90%; physician-reported, 88%). Most patients reported the effects of Solriamfetol to last ≥6 hours (81%) with no change in their night-time sleep quality (86%). Common adverse effects were headache, insomnia, and irritability.

Conclusion

These real-world data describe the use of solriamfetol in a cohort of German patients with OSA. Solriamfetol was typically initiated at 37.5 mg/day; titration was common. ESS improvements were greater than the minimum clinically important difference (MCID) of 2-3, and most patients and physicians perceived improvement in EDS. Common adverse events were consistent with those previously reported for solriamfetol.

Support (if any)

Axsome Therapeutics and Jazz Pharmaceuticals
0563 The Evaluation of a Revolutionary Custom-Made Oral Appliance Design on Effectiveness, Efficacy, and Compliance
Authors: Ojile Joseph , Uhles Matthew , Postol Kevin , Lillenberg James , Alisic Sabina , Gonzalez Alexis
Published: May 2023

Introduction

Evaluate the clinical effectiveness of the SomnoDent Avant with Bflex technology, a custom-made oral appliance therapy (OAT) device in the treatment of mild/moderate Obstructive Sleep Apnea (OSA) for naïve and PAP non-compliant patients. Hypothesis for the study was that the unique strap mechanism design of the appliance encouraged mouth closure and nasal breathing, would have high levels of effectiveness, particularly for supine sleepers. The evaluation of the initial fit of the device as well as patient’s and bed partner’s acceptance were also investigated

Methods

Prospective 90 day trial, participants age ≥ 18 with AHI of ≥10 to ≤30 events/hr. confirmed by using a WatchPAT, Home Sleep Apnea Testing (HSAT) device at baseline. Initial advancement of the lower jaw was 60%. Treatment effectiveness is derived from two endpoints: efficacy and compliance. The efficacy of the OAT is defined as the change from baseline in AHI, based on one and three-month HSAT. Efficacy was measured in supine, lateral and prone positions. Compliance data was obtained from the Dentitrac (BRAEBON Medical Corporation) chip embedded in the SomnoDent Avant device looking at usage for at least 4 hours per night for at least 5 out of 7 nights a week.

Results

Preliminary data from 50 participants (66% male, 35% female), age: 52.3 ± 11.8 yrs., BMI: 31.1. A statistically significant 3-month trend change from baseline AHI -11.0 ± 7 (37/37), Average usage:7.0hrs/night, ESS: 3 month change from baseline -3.3 ± 4.0 (80.0% improvement), FOSQ 10: 1.7 ± 2.2 (76.7% improvement). Adequate (first-time) fit of the device upon initial insertion 89.3%, bed partner sleep improvement 83.3%, and 88.9% would recommend the use of the Avant OAT device.

Conclusion

• SomnoDent Avant demonstrated high effectiveness in the treatment of OSA, particularly with supine dependent OSA participants. The unique design of the Avant strap likely acts to close the patient’s mouth, encouraging nasal breathing • Statistical improvement in the quality of life • Optimum first-time fit • Improvement in bed partner quality of sleep

Support (if any)

SomnoMed
0565 The Obstructive Sleep Apnea CPAP Therapy Compliance; Progressions, Challenges and Interventions
Authors: Khalili Kianoush
Published: May 2023

Introduction

Obstructive sleep apnea (OSA) is a common sleep disorder affecting 26% of the United States adult population and is associated with adverse health outcomes. Despite the advent of an array of treatment options, PAP remains the primary treatment modality for OSA since the approach was introduced in 1981. The objective of this systematic review is to determine how we can increase compliance to PAP therapy as the gold standard of OSA treatment.

Methods

A systematic review was conducted to study meta-analyses performed to determine the clinical significance of using PAP in several modalities, PAP initiation strategies, educational and behavioral interventions, tele monitoring, humidification, level of AHI, different mask interfaces, and flexible or modified pressure profile PAP to treat OSA in adults.

Results

Data demonstrated a clinically significant improvement in PAP adherence with the use of educational, behavioral, troubleshooting, and telemonitoring interventions. Also systematic reviews show that nasal interfaces compared to oronasal interfaces have improved adherence and slightly greater reductions in OSA severity, heated humidification compared to no humidification reduces some continuous PAP-related side effects. Finally, AHI level of 15 and above but not demographic variables payed a role in compliance.

Conclusion

All medical therapies have challenges with patient adherence. PAP therapy for OSA has unique challenges as available data indicate that optimal benefit is derived from continued use throughout the patient's sleeping period while clinical trials continue to demonstrate suboptimal group adherence ranging from 3–5 h/night. Given this, substantial work remains to be done to determine the optimal combination of strategies to maximize adherence. All researches on increasing adherence has evaluated outcomes at 3 months or less, despite evidence that usage continues to wane over time long-term. Evaluation of strategies to maintain adherence long term is a critical research priority. Other fields to focus are strategies for identification of patient-factors that place them at risk for nonadherence prior to PAP use, and the development and validation of specific algorithms to utilize with telemonitoring to identify nonadherent patients early after initiation of PAP. Comparative effectiveness studies will be needed to develop a comprehensive adherence program that can be deployed into routine clinical care.

Support (if any)
0566 The Usefulness of ApneaLinkTM as a Screening Test for Diagnosis of Obstructive Sleep Apnea
Authors: Kim Sangjun
Published: May 2023

Introduction

To investigate the usefulness of ApneaLinkTM as a screening test for obstructive sleep apnea by analyzing the correlation between ApneaLinkTM and polysomnography (PSG).

Methods

From January 1, 2018 to December 31, 2020, patients who visited the sleep clinic with snoring, sleep apnea, and excessive daytime sleepiness at the otolaryngology department of this hospital were subjected to both standard sleep PSG and ApneaLinkTM. Correlations of Apnea-Hypopnea Index (AHI) and Respiratory Disturbance Index (RDI) in standard PSG with AHI and Risk Indicator (RI) in ApneaLinkTM were investigated. To determine the usefulness of ApneaLinkTM as a screening test for patients with moderate or severe sleep apnea, cut-off values of AHI and RI of ApneaLinkTM were determined using receiver operating characteristic (ROC) curves.

Results

The correlation coefficient between AHI in PSG and AHI or RI in ApneaLinkTM was both 0.647, showing a high positive correlation. The correlation coefficient between RDI in PSG and AHI or RI in ApneaLinkTM was both 0.637, showing a high positive correlation. When the cut-off value of AHI with the ApneaLinkTM test was 19.0, it showed a sensitivity of 76.29% and a specificity of 78.95%, which could be expected to produce more than 15 of RDI in PSG.

Conclusion

Through this study, it was found that ApneaLinkTM could be used as a screening test for obstructive sleep apnea.

Support (if any)
0568 Trends in OSA Disease Severity Over Nearly Two Decades: Update on the VA San Diego Experience
Authors: Nokes Brandon , Zamora Tania , Cervantes-Gameros Cesar , Perrine William , Barker Robert , Stepnowsky Carl
Published: May 2023

Introduction

The Veterans Health Administration (VA) is one of the largest integrated healthcare systems in the United States. Key risk factors for obstructive sleep apnea (OSA) include aging, weight, and male gender, all of which are highly prevalent in the VA population and help to explain the higher rates of OSA in the VA. The Pulmonary Sleep Program at the VA San Diego Healthcare System (VASDHS) started a patient database over twenty years ago for its home sleep apnea testing (HSAT) program. An analysis of ten years of diagnostic HSAT data was reported on over 12,500 patients in 2014. This analysis focuses on an update on the last four years and a comparison to 2014.

Methods

A retrospective review of the local clinical database of HSAT diagnostic testing was conducted. The database contained 8,928 sleep studies from 2018 to 2022. Invalid studies were removed. Only initial diagnostic studies were included.

Results

Of the 8,928 diagnostic studies, 2,564 tested negative for OSA (28.7%). Of the 6,364 positive cases, 43.3% were mild, 28.8% were moderate, and 27.9% were severe. The percentages of each OSA severity level were stable across these years (mild: 42%-45%; moderate: 27%-32%; and severe: 26%-29%). The mean AHI did not significantly change from 2018 (24.1+/-20.6) to 2022 (25.1+/-21.2) (overall mean 24.4+/-20.3; range: 5-140).

Conclusion

Based on this extensive retrospective review of diagnostic testing at a single, high-volume HSAT program, it appears that OSA severity levels have stabilized over these past five years, with the highest percentage of mild OSA cases (~43%) followed by moderate (~29%) and severe (~28%). Our facility saw a significant decrease in severe cases (60% to 30%) and increase in mild OSA (7% to 35%) from 2004 to 2013. Today, over 4 out of every 10 new OSA diagnoses are mild, which has significant treatment implications given that adherence to the two primary medical device options is suboptimal. Identifying patient-centered treatment options for these patients is a priority.

Support (if any)

VA RR&D D2651-R and the Sleep Medicine Section of the VA San Diego Healthcare System supported this project.
0575 Cataplexy Response With FT218 (Once-Nightly Sodium Oxybate): Post Hoc Responder Analysis From the Phase 3 Rest-ON Clinical Trial
Authors: Thorpy Michael , Kushida Clete , Ajayi Akinyemi , Dubow Jordan , Gudeman Jennifer
Published: May 2023

Introduction

In the phase 3 REST-ON trial (NCT02720744), participants with narcolepsy type 1 (NT1) treated with once-nightly sodium oxybate (ON-SXB; FT218), an investigational, extended-release formulation, had significant reductions in cataplexy episodes (ON-SXB vs placebo: 4.5 g, P< 0.05 [post hoc]; 6 , 7.5, and 9 g, all P< 0.001). This post hoc responder analysis further characterized improvements in mean weekly cataplexy episodes in trial participants.

Methods

In REST-ON, participants aged ≥16 years with NT1/NT2 were randomized 1:1 to double-blind ON-SXB or placebo for 13 weeks. Participants took 4.5 g (1 week), 6 g (2 weeks), 7.5 g (5 weeks), and 9 g (5 weeks). Participants with NT1 recorded number of cataplexy episodes per day (0, 1, 2, 3, 4, or ≥5) in a diary. Percentage of participants with ≥25%, ≥50%, ≥75%, and 100% reductions in weekly cataplexy episodes from baseline were compared (ON-SXB vs placebo; Fisher exact test).

Results

In the modified intent-to-treat population, 145 participants had NT1 (ON-SXB, n=73; placebo, n=72). Baseline mean (SD) number of weekly cataplexy episodes was 18.9 (8.7) for the ON-SXB group and 19.8 (8.9) for placebo. At week 1 (4.5 g), significantly more participants taking ON-SXB had ≥25% reduction in cataplexy (43.8% vs 26.4%; P< 0.05). Significantly more participants receiving ON-SXB had ≥25%, ≥50%, or ≥75% reduction in cataplexy vs placebo at weeks 3, 8, and 13 and complete resolution of cataplexy at weeks 8 and 13 (6-g dose: ≥25%, 68.5% vs 40.3% [P< 0.001]; ≥50%, 38.4% vs 20.8% [P< 0.05]; ≥75%, 23.3% vs 4.2% [P=0.001]; 100%, 2.7% vs 0 [P=NS]; 7.5-g dose: ≥25%, 67.1% vs 43.1%; ≥50%, 53.4% vs 25.0%; ≥75%, 32.9% vs 8.3% [all P< 0.001]; 100%, 6.8% vs 0 [P< 0.05]; 9-g dose: ≥25%, 58.9% vs 41.7% [P< 0.001]; ≥50%, 49.3% vs 26.4% [P< 0.001]; ≥75%, 32.9% vs 15.3% [P< 0.01]; 100%, 11.0% vs 2.8% [P< 0.05]).

Conclusion

In this post-hoc analysis, ON-SXB 4.5 g significantly reduced cataplexy by week 1. Additionally, ~10% of participants taking ON-SXB 7.5 and 9 g were free of cataplexy episodes. These data may be useful for clinicians when setting expectations of ON-SXB effectiveness for patients with cataplexy.

Support (if any)

Avadel Pharmaceuticals
0579 Long-Term Safety of Once-Nightly Oxybate for Narcolepsy: RESTORE Study Interim Analysis of Data
Authors: Stern Thomas , Roy Asim , Shapiro Colin , Harsh John , Ajayi Akinyemi , Ibrahim Sally , Dubow Jordan , Gudeman Jennifer
Published: May 2023

Introduction

The pivotal phase 3 REST-ON trial (NCT02720744) evaluated the efficacy and safety of once-nightly sodium oxybate (ON-SXB; FT218), an investigational extended-release formulation for treatment of adults with narcolepsy. In REST-ON, ON-SXB met its 3 coprimary endpoints: improvement in mean sleep latency on the Maintenance of Wakefulness test, Clinical Global Impression-Improvement rating (% much/very much improved), and number of weekly cataplexy attacks at all doses tested (P< 0.001 vs placebo). The safety profile of ON-SXB was consistent with that of immediate-release (IR) SXB. The ongoing RESTORE trial (NCT04451668) is an open-label/switch study evaluating the safety and tolerability of ON-SXB.

Methods

Participants aged ≥16 years with narcolepsy type 1 or 2 who completed the REST-ON trial, were on stable-dose (≥1 month) IR oxybate, or were oxybate-naive are eligible for RESTORE. Initial doses were 4.5 g/night or equivalent/closest to the previous total IR oxybate dose/night for those switching; incremental adjustments (1.5 g/week; maximum dose, 9 g/night) were allowed. Safety data for participants receiving ≥1 dose of ON-SXB as of 01 July 2022 are reported here.

Results

This analysis includes interim data from 180 participants (REST-ON participants, n=15 [8.3%]; oxybate-naive, n=35 [19.4%]; switch, n=130 [72.2%]). Most participants are white (n=150 [83.3%]) and female (n=122 [67.8%]); mean age is 35 years [range, 16–84]). Most participants who reported an adverse event (AE; n=105 [58.3%]) had AEs that were mild (61.9%) or moderate (32.3%) in severity. Three participants had serious AEs (abscess, deep vein thrombosis, rib fracture and pneumothorax); all were deemed unrelated to ON-SXB and all 3 participants continued in the study. Adverse drug reactions (ADRs; ie, AEs related/possibly related to study drug) were reported by 76 (42.2%) participants with 6 (3.3%) participants discontinuing ON-SXB owing to ADRs. ADRs occurring in ≥3% of participants were nausea (11.7%), somnolence (6.7%), headache (5%), enuresis (5%), somnambulism (3.9%), dizziness (3.9%), tremor (3.9%), and vomiting (3.3%).

Conclusion

Interim data from the RESTORE study indicate that ON-SXB is generally well tolerated with a low rate of discontinuation owing to ADRs. If granted final FDA approval, ON-SXB will offer adults with narcolepsy a once-at-bedtime oxybate treatment option.

Support (if any)

Avadel Pharmaceuticals