bluuebunny/crossref_metadata_2025 huggingface dataset:
0547 Phenotyping of Obstructive Sleep Apnea and its Difference in mortality
Authors: Seo Min Cheol , Shin Jiyoon , Lee Kyung Hwa , Jeon Jeong Eun , Lee Ha Young , Park Cho Won , Kim Sun-Young , Lee Yu Jin
Published: May 2023

Introduction

Obstructive sleep apnea (OSA), which is associated with a high mortality, is a heterogeneous disease that is affected by various pathophysiology. Although the severity of OSA is divided based on apnea-hypopnea index (AHI), AHI alone did not sufficiently represent these pathologies. The objective of this study is to categorize OSA using PSG data and compare the characteristics of each group including mortality.

Methods

7,247 subjects were recruited at the Center for Sleep and Chronobiology, Seoul National University Hospital from June 2004 to December 2021. Demographic data, polysomnography, Sleep scale including Epworth sleepiness scale, Pittsburgh sleep quality index, Beck depression inventory, and Beck anxiety inventory were performed. After categorizing OSA using K-mean cluster analysis, Kaplan-Meir survival analysis and Cox proportional hazard regression analysis were used to evaluate all-cause mortality and hazard ratios.

Results

Three clusters were identified; Cluster 1 was associated with moderate OSA (mean AHI=19.28/h), high sleep efficiency and low arousal, Cluster 2 with moderate OSA (mean AHI=24.81/h), low sleep efficiency and high arousal, Cluster 3 with the most severe OSA (mean AHI=64.76/h), obese, and decreased O2 saturation. Conventional classification of OSA showed no difference in mortality between group, whereas Cluster 1 and Cluster 3 showed significant higher all-cause mortality compared to not-OSA group (Cluster 1, Log rank p=0.008; Cluster 3 Log rank p< 0.001). The risk of mortality was also significantly increased in cluster 1 (HR 2.048, 95% CI 1.265-3.317, p=0.004) and cluster 3 (HR 3.686, 95% CI 1.871-7.262, p< 0.001). These results were also observed after adjustment for sex, age, BMI and comorbid disease (Cluster 1, HR 2.053, 95% CI 1.197-3.518, p=0.009; Cluster 4, HR 2.640, 95% CI 1.230-5.666, p=0.012).

Conclusion

Phenotyping of OSA considered multiple variables is more appropriate to predict mortality than conventional classification based on AHI. In addition to evaluate patient with severe OSA, patients with moderate OSA who shows relatively good sleep and low arousal should be cautiously evaluated and monitored.

Support (if any)

This study was supported by the Technology Innovation Infrastructure program through the Korea Institute for Advancement of Technology funded by the Ministry of Trade, Industry and Energy.(study no.: P0014279, 20009210, Dr. Yu Jin Lee)
0549 Positive Airway Pressure for Obstructive Sleep Apnea in Systolic Heart Failure Patients Reduces Healthcare Resource Utilization
Authors: Kuniyoshi Fatima Sert , Malhotra Atul , Cole Kate , Malik Anita , Pépin Jean-Louis , Cistulli Peter , Benjafield Adam , Somers Virend
Published: May 2023

Introduction

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

Methods

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

Results

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

Conclusion

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

Support (if any)

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

Introduction

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

Methods

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

Results

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

Conclusion

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

Support (if any)

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

Introduction

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

Methods

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

Results

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

Conclusion

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

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

Introduction

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

Methods

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

Results

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

Conclusion

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

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

Introduction

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

Methods

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

Results

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

Conclusion

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

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

Introduction

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

Methods

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

Results

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

Conclusion

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

Support (if any)

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

Introduction

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

Methods

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

Results

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

Conclusion

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

Support (if any)

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

Introduction

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

Methods

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

Results

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

Conclusion

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

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

Introduction

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

Methods

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

Results

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

Conclusion

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

Support (if any)

Avadel Pharmaceuticals
0591 Effectiveness and Optimization of Lower-Sodium Oxybate in Participants With Narcolepsy Switching From Sodium Oxybate (SEGUE)
Authors: Leary Eileen , Pfister Craig , Fuller Douglas , Macfadden Wayne
Published: May 2023

Introduction

Lower-sodium oxybate (LXB, Xywav®) contains 92% less sodium than higher-sodium oxybate (SXB, Xyrem®) and is approved for treating cataplexy or excessive daytime sleepiness in patients with narcolepsy (≥7 years of age) and idiopathic hypersomnia in adults. The SEGUE study examines the safety, tolerability, effectiveness, and treatment optimization in participants with narcolepsy transitioning from SXB to LXB.

Methods

Eligible participants in this multicenter, open-label study were adults with narcolepsy type 1 or 2 who were on a stable dose (maximum 9 g/night; no single dose >6 g) and regimen (once, twice, or thrice nightly) of SXB. After 2 weeks on a stable SXB dose/regimen (baseline period), participants switched to the same dose/regimen of LXB (intervention period; 6 weeks). If needed, LXB dose/regimen was titrated to optimize efficacy/tolerability. Assessments included the Patient Global Impression of Change (PGIc), a forced preference questionnaire (FPQ), an ease of switching medication scale (EOSMS), and the Epworth Sleepiness Scale (ESS); all collected at end of treatment or early discontinuation.

Results

Of 60 participants who entered the intervention period, a majority were female (62%) and White (88%); mean (SD) age was 43.9 (15.33) years. Starting and ending (end of treatment or early discontinuation) median total nightly doses of LXB were 8.5 g and 9.0 g, respectively. In terms of regimen, most took LXB twice nightly (93% at both time points). Fifty-six participants completed the transition period; mean (SD) time to stable dose was 2.5 (4.82) days, and median (range) number of changes in dose/regimen was 0.0 (0, 1). At end of treatment or early discontinuation, most participants reported improvement (very much/much/minimal; 45%) or no change (48%) in narcolepsy symptoms on the PGIc, preferred LXB over SXB on the FPQ (79%), and reported the transition to LXB was easy, extremely easy, or not difficult at all on the EOSMS (93%). Mean (SD) change from baseline on the ESS (n=55) was −0.7 (2.31).

Conclusion

Most participants with narcolepsy switched from SXB to LXB with minimal modifications of dose/regimen and reported the transition process was easy. Effectiveness of oxybate treatment (ESS) was maintained after transition, and most preferred LXB over SXB.

Support (if any)

Jazz Pharmaceuticals.
0595 Long-term efficacy on cataplexy attacks and excessive daytime sleepiness in open-label extension study (NLS-1022) of mazindol ER
Authors: Stern Thomas , Corser Bruce , Bogan Richard , Franco Jennifer , Konofal Eric , Apostol George , Rosenberg Russell , Morse Anne , Thorpy Michael , Kushida Clete
Published: May 2023

Introduction

Mazindol ER (extended-release), the first partial orexin-2 receptor agonist and triple mono-aminergic reuptake inhibitor, has demonstrated efficacy and safety in significantly reducing excessive daytime sleepiness (EDS) and cataplexy attacks in narcolepsy type 1 (NT1) and type 2 (NT2) patients (POLARIS, Study NLS-1021). This efficacy was further studied in an open-labeled extension (OLE) study (ClinicalTrials.gov Identifier: NCT04923594).

Methods

A multicenter, 6-month, OLE study with 51 narcolepsy patients previously enrolled in a double-blind mazindol ER study. Patients were administered 3mg mazindol ER once daily in the morning. Narcolepsy symptoms and adverse events were recorded. Safety measures included monthly physical and laboratory examinations. The primary efficacy measure was the change from baseline in EDS using the Epworth Sleepiness Scale (ESS). Secondary measures included weekly cataplexy attacks, the overall disease severity as rated by the investigators (Clinician Global Impression of Severity) and patients (Patient Global Impression of Severity).

Results

Mazindol ER at 3 mg once-daily doses, produced overall improvements in EDS and narcolepsy within 1-2 weeks of starting dosing. Reported improvements included diminished daytime sleepiness (p < 0.001); significant decreases in cataplexy attacks (p < 0.001); and multiple improvements in symptoms severity and function. Adverse events were generally mild and patients showed no evidence of tolerance.

Conclusion

Mazindol ER is a convenient, safe, well-tolerated and effective treatment for narcolepsy. Its anticataleptic and wake-promoting effects indicate that it may be a new therapeutic option for patients with NT1 or NT2 similar or better than various combinations treatments currently available.

Support (if any)

NLS Pharmaceutics
0597 Path to Diagnosis and Impact of Narcolepsy on Quality of Life: A Survey of People Living With Narcolepsy
Authors: Ortiz Luis , Morse Anne , Krahn Lois , Lavender Maggie , Horsnell Matthew , Cronin Dianna , Schneider Beth , Gudeman Jennifer
Published: May 2023

Introduction

Research was undertaken to better understand the path to a narcolepsy diagnosis, common symptoms, and the impact of narcolepsy on work, social interactions, and mental health.

Methods

In February 2022, an email invitation to an online, 27-question survey was sent to US members of MyNarcolepsyTeam, a social network of >9,800 members.

Results

In total, 110 members completed the survey. 38% of respondents started to experience symptoms before reaching 16 years of age. Most commonly experienced symptoms included excessive daytime sleepiness (EDS; 93%) and fatigue (84%). In total, 72% were also experiencing some form of sleep disturbance and 67% were already suffering from cognitive/memory challenges. 68% who were eventually diagnosed with narcolepsy type 1 (NT1) had cataplexy attacks. For 31%, getting to a narcolepsy diagnosis took ≥10 years. In fact, 64% were initially under- or misdiagnosed with something other than narcolepsy, including depression (73%), sleep apnea (36%), or attention-deficit/hyperactivity disorder (16%). 74% of patients with NT1 have continued to experience cataplexy, with 46% having some form of a cataplexy episode a few times per week. Cataplexy episodes were triggered by a wide range of emotional situations, including over-tiredness (70%), anger (48%), being startled (46%), laughter (46%), fear (44%), excitement (38%), or crying (33%). 76% of respondents indicated that the impact of narcolepsy on daily life is extremely or very severe. The far-reaching impact on quality of life was evident in that most respondents reported that narcolepsy interfered with work (82%), social life (86%), everyday chores (85%), and exercise (85%) and has limited career options (76%). The emotional toll of narcolepsy manifested in feeling isolated (83%), depressed (81%), anxious (80%), or embarrassed (75%).

Conclusion

Patients routinely experienced a misdiagnosis or a “missed” diagnosis based on common symptoms experienced. Being able to quickly identify narcolepsy as the root cause for symptoms of EDS, fatigue, and sleep disturbances can lead to getting the patient on the best treatment path as early as possible. Understanding the physical, emotional, and quality-of-life impact of narcolepsy can help clinicians provide a more holistic approach to treating their patients.

Support (if any)

Avadel Pharmaceuticals
0598 Patient-Reported Sleep Quality in People With Narcolepsy Transitioning From Sodium Oxybate to Lower-Sodium Oxybate
Authors: Husain Aatif , Zee Phyllis , Leary Eileen , Macfadden Wayne , Fuller Douglas , Candler Shawn , Bae Charles
Published: May 2023

Introduction

Lower-sodium oxybate (LXB; Xywav®), which contains the same active moiety as higher-sodium oxybate (SXB; Xyrem®) but with 92% less sodium, is approved by the US Food and Drug Administration (FDA) for treating cataplexy or excessive daytime sleepiness in patients ≥7 years of age with narcolepsy. LXB is recognized as clinically superior to SXB in narcolepsy by the US FDA due to lower chronic sodium exposure. Real-world data related to sleep quality following transition from SXB to LXB are lacking.

Methods

Transition Experience of persons with Narcolepsy taking Oxybate in the Real-world (TENOR; NCT04803786) was a patient-centric, prospective, observational, noninterventional, virtual-format study of US adults with narcolepsy (type 1 or 2) transitioning from SXB to LXB within the previous/upcoming 7 days. Longitudinal data collected during transition and for 21 weeks thereafter were based on daily and weekly questionnaires and sleep diaries instructing participants to rate the quality of their sleep and how refreshed they felt upon waking, and to record their sleep latency, wake after sleep onset (WASO), time in bed (TIB), and total sleep time (TST).

Results

The mean (standard deviation [SD]) age of the 85 participants (narcolepsy type 1, n=45; narcolepsy type 2, n=40) was 40.3 (13.0) years; most were female (73%) and White (87%). Almost all participants took SXB (82/85, 96%) twice nightly prior to transition and LXB (82/84, 98%) twice nightly after transition. Most participants rated their sleep quality as “good” or “very good” at baseline (45/84, 54%) and end of study (38/71, 54%), while 24/84 (29%) and 30/71 (42%) reported feeling “well-rested” or “very well-rested” at baseline and end of study, respectively. At end of study, changes (n=71) in mean (SD) sleep latency, WASO, TIB, and TST were −10.5 (16.2), −14.8 (56.6), 7.6 (67.7), and 33.0 (93.8) minutes, respectively.

Conclusion

Although participant-reported sleep quality was generally unchanged during the study, a greater percentage of participants reported feeling refreshed at end of study (on LXB) than at baseline (on SXB); however, there was no non-transitioning arm for comparison. Small changes were noted at end of study in sleep parameters, including sleep latency, WASO, and TST.

Support (if any)

Jazz Pharmaceuticals
0606 Fatigue or excessive daytime sleepiness, which is more related with depression?
Authors: Yang Kwang Ik , Yim Soo Hwan , Lee Seung Cheol , Kim Daeyoung , Chu Min Kyung , Yun Chang-Ho
Published: May 2023

Introduction

Fatigue and excessive daytime sleepiness (EDS) were often regarded as having almost similar meaning in routine daily life. However, these two terms are strictly distinct concepts. The effect on depression between EDS and fatigue, which coexist depending on the situation or exist individually. We aimed to investigate both fatigue and EDS were classified in detail to determine which is more related to depression in the general population.

Methods

A total of 2,493 participants (female: 1,257) (47.90 ± 0.33 years old) were investigated nationwide, across 15 South Korean districts using face-to-face interviews survey. Fatigue, EDS, and depression were evaluated using the Fatigue Severity Scale (FSS), Epworth sleepiness scale (ESS), and Patient Health Questionnaire-9 (PHQ-9), respectively. The covariates such as sleep habits and socio-behavioral factors were included.

Results

The prevalence of depression (PHQ-9 ≥ 10) was 8.42% (n = 210). Fatigue (FSS ≥ 36) was 30.8% (n = 767). EDS (ESS ≥ 11) was 15.3% (n = 382). The prevalence of depression was following four categories; EDS with fatigue (E+F+) (n = 67, 31.9% vs. 7.3%) (P < 0.001), fatigue without EDS (E-F+) (n = 71, 33.8% vs. 20.3%) (P < 0.001), EDS without fatigue (E+F-) (n= 16, 7.6% vs. 5.8%) (P = 0.294), and absence of fatigue and EDS (E-F-) (n = 56, 26.7% vs. 66.6%) (P < 0.001). After adjusting for covariates, the presence of depression (E-F-, reference) was associated with E+F+ (OR 8.804, 95% CI 5.818-13.321), E-F+ (OR 3.942, 95% CI 2.704-5.747), and E+F- (OR 2.812, 95% CI 1.542-5.131). We additionally performed logistic regression according to two categories. There was no significant difference of prevalence of depression between E+F- (reference) and E-F+ (OR 1.399, 95% CI 0.760-2.575).

Conclusion

Although fatigue and EDS were associated with depression regardless of the presence of each other. But we did not find out which is more related with depression.

Support (if any)
0624 Sleep Duration and Insomnia Predict Increases in Depression in Adolescents at Subsequent 3-Month Intervals: A Longitudinal Study
Authors: Hijazi Joud , Oryschkewych Nina , Hafer Bethany , Kristo Grant , Wallace Meredith , Goldstein Tina , Buysse Daniel , Franzen Peter
Published: May 2023

Introduction

Adolescence is a critical developmental period for mental health, with the incidence of depression increasing significantly during this period. Both short sleep duration and insomnia are common and associated with depression risk. Longitudinal studies examining the relationship between sleep and depression in adolescents are scarce; therefore, the current study investigates the influence of sleep duration and insomnia on future increases in depressive symptoms.

Methods

A community sample of 151 never-depressed healthy adolescents (56.3% female; mean age = 14) were enrolled in 7th-9th grade (ages 11-15 years old) and followed for up to two years. On-line self-report questionnaires were collected every 3 months, including the Center of Epidemiology Studies Depression Scale (CES-D), the Insomnia Severity Index (ISI), and the Sleep Timing Questionnaire (STQ). The sleep item was excluded from the CES-D score used for analysis. Sleep duration was estimated through reported usual time in bed on the STQ (weighted average of weekdays and weekends). Separate mixed effects analyses examined whether time in bed or ISI predicted CES-D scores 3 months later, controlling for gender, age, and lag CES-D.

Results

Depression was associated with both time in bed (t(736)=-2.8, p< 0.005) and Insomnia Severity Index (t(736)=2.3, p=0.02). For every one standard deviation decrease in time in bed, depression was predicted to increase by 0.15 points 3 months later. For every one standard deviation increase in Insomnia Severity Index, depression was predicted to increase by 0.12 points 3 months later.

Conclusion

The findings suggest that lower time in bed and higher insomnia predict increases of depression in the following 3 months. Given that sleep is a modifiable risk factor for depression, improving sleep health may help ameliorate depression during this high-risk period.

Support (if any)

Source of support is the National Institutes of Health (R01 MH118312).
0636 Examination of longitudinal chronotype stability in individuals with bipolar disorder and healthy controls
Authors: Sperry Sarah , Boland Elaine , Burgess Helen , Gonzalez Robert , Gonzalez Suzanne , Lane Jacqueline , McCarthy Michael , Menkes Margo , Murphy Victoria , Gehrman Philip
Published: May 2023

Introduction

Introduction: Circadian rhythms have long been conceptualized as central to the pathophysiology of bipolar disorder (BD). Numerous cross-sectional analyses have demonstrated associations of eveningness with BD and greater severity of mood symptoms. Longitudinal studies that evaluate stability of chronotype and its association with mood symptoms are lacking.

Methods

88 BD2) from the Prechter Longitudinal Study of BD. Participants completed an average of 10 years of longitudinal assessments of depression (PHQ-9) and mania (Altman Self-Reported Mania Scale) every 2 months, and chronotype (Munich ChronoType Questionnaire) annually. Chronotype was assessed using both a single item from the MCTQ in which seven possible chronotypes were presented (from extreme early to extreme late type), and the calculation of midpoint of sleep on work-free days, sleep-corrected (MSFsc). We calculated (in)stability using the mean square successive difference (MSSD) and assessed the relationship between mood, age, sex, medication, and stability using mixed effects models.

Results

Results: Individuals with BD1 and BD2 reported later chronotypes compared to HC. Individuals with BD1 had later MSFsc as well as greater instability in chronotype and MSFsc compared to HC. Greater instability in chronotype was associated with higher depression and mania symptom severity. Treatment with mood stabilizers was associated with less instability in MSFsc, while antidepressant treatment was associated with greater instability in MSFsc.

Conclusion

Discussion: These results provide the strongest evidence to date of later chronotypes in individuals with BD. This is the largest examination of longitudinal stability of chronotype and results indicate that only BD1 is associated with greater instability over time. This instability, in part, reflects changes in mood symptoms over time, as well as in medication use. These data highlight the importance of assessment and treatment of circadian disruption in individuals BD.

Support (if any)

Heinz C. Prechter Bipolar Research Program
0638 Comparison of social jet lag between individuals with seasonal affective disorder and controls
Authors: Hine Kaylee , Wescott Delainey , Klevens Alison , Taylor Maddison , Roecklein Kathryn
Published: May 2023

Introduction

Social jet lag (SJL) occurs when a person’s social time (weekdays) is out of phase with their circadian time (weekend). Not much is known about the relationship between Seasonal Affective Disorder (SAD) and SJL; however, the sleep/wake cycle is very vulnerable to disruption by external factors. In a previous study in adolescents and young adults, self-reported chronotype was used to calculate SJL, and winter mood variation and SJL were found to be higher after the time change in fall and winter. Our study will directly compare SAD and non-depressed controls in the winter on SJL calculated with actigraphy in a sample of adults.

Methods

Participants (N=46) ages 21-64 were recruited during winter months and included individuals with SAD (n=21) and nonseasonal, never depressed controls (n=25). Midsleep timing was measured using actigraphy (average number nights = 7), and SJL was calculated by subtracting average week midsleep from average weekend midsleep corrected for number of days. Regression analysis included diagnostic group as a predictor, age and gender as covariates, and SJL as the outcome.

Results

While the seasonally depressed group had a slightly higher average SJL (M =61.8 minutes, SD = 181.2 minutes) than the control group (M = 60.6 minutes, SD = 165 minutes; mean difference 1.2 minutes), there was no significant difference in SJL between the participants with seasonal depression and the controls (p=0.778). However, age was a significant predictor, as the younger half of the sample had a mean SJL of 94 minutes (SD=180 minutes) and the older half of the sample had a mean SJL of 24 minutes (SD= 156 minutes; mean difference= 70 minutes). There was no group*age interaction in post-hoc tests.

Conclusion

This is the first study to test whether individuals with SAD have greater SJL than non-depressed controls, and the data do not support such a hypothesis. Results do, however, confirm prior findings that SJL decreases with age. Future studies should compare SJL in individuals with SAD during winter compared to spontaneous summer remission to test whether a change in SJL correlates with winter depression onset.

Support (if any)

NIMH K.A.R. MH103303
0645 Prevalence of sleep disorders and their association with posttraumatic stress and anxiety symptoms among college students
Authors: Roeper April , Covington Lauren , Ji Xiaopeng , Brownlow Janeese
Published: May 2023

Introduction

Incidence of diagnosed psychiatric disorders tend to peak during early adulthood. Furthermore, sleep complaints are highly prevalent among college students, and often exacerbate psychiatric disorders. This study aimed to explore the prevalence of sleep disorders, and their association with posttraumatic stress disorder (PTSD) and generalized anxiety disorder (GAD) symptoms among college students.

Methods

College students completed self-report measures as part of a larger study (n=56; mean age 20.23 (SD=1.5); 83.9% females). The SLEEP-50 questionnaire estimated the prevalence of sleep disorders. Each sleep disorder required a cutoff score and at least one sleep complaint, with a minimum score of three or four used to classify a sleep complaint. The GAD-7 scale assessed for generalized anxiety disorder symptoms, and the PCL-5 determined PTSD symptomatology. Linear regression models identified the association between each sleep disorder on posttraumatic stress and generalized anxiety symptoms.

Results

Approximately 19.6% of students were at risk for at least one sleep disorder. The most frequent sleep disorder was hypersomnia (69.5%), followed by narcolepsy (53.6%), insomnia (48.2%), affective disorder (28.6%), and restless leg syndrome (21.4%). In contrast, circadian rhythm disorder (16.1%) and sleep apnea (7.1%) were infrequently reported. Linear regression models indicated that affective disorder (t=2.83, p<.007; t=3.13, p<.003) and hypersomnia disorder (t=2.31, p=.025; t=2.39, p=.020) significantly predicted PTSD and GAD symptoms respectively. Additionally, insomnia (t=3.97, p<.001) and restless leg syndrome (t=2.34, p=.023) were significant predictors for GAD only, and circadian rhythm disorder (t=2.760, p=.008) was a significant predictor for PTSD only.

Conclusion

Results suggest that risk of sleep disorders was significantly associated with PTSD and GAD symptoms in college students. Given these findings, health promotion programs are needed to promote good sleep hygiene and early interventions for mental health during college years.

Support (if any)

This study was funded by a Center Grant from the National Institutes of General Medical Sciences (Grant # P20GM103653).