bluuebunny/crossref_metadata_2025_split huggingface dataset:
0431 Different physiological characteristics of obstructive sleep apnea symptom subtypes across international sleep centers
Authors: Keenan Brendan , de Chazal Philip , Penzel Thomas , Gerardy Bethany , Magalang Ulysses , Younes Magdy , Mazzotti Diego , Pack Allan 
Published: May 2023

Abstract

Introduction
Obstructive Sleep Apnea (OSA) is a widespread and heterogeneous sleep disorder. Studies have identified reproducible subtypes of OSA based on patient-reported symptoms that have different cardiovascular outcomes. Prior data showed similar apnea-hypopnea index (AHI) across subtypes; however, other physiological characteristics have not been comprehensively compared among these subtypes.

Methods
1,285 participants from the Sleep Apnea Global Interdisciplinary Consortium (SAGIC) with moderate-severe OSA (AHI≥15) were included. Differences in traditional and novel physiological traits were compared among the Disturbed Sleep (n=183 [14.2%]), Minimally Symptomatic (n=581 [45.2%]), and Excessively Sleepy (n=521 [40.5%]) subtypes using analysis of covariance (ANCOVA) adjusted for age, sex, BMI and race/ethnicity. Measures included AHI and other respiratory event indices, hypoxic burden, oxygen characteristics, sleep/wake amounts, electroencephalogram (EEG) spectral characteristics, including metrics related to the odds ratio product (ORP; a validated index of sleep depth ranging from 0.0 [deep sleep] to 2.5 [full wakefulness]), arousal intensity, and heart rate response to arousal.

Results
Compared to other subtypes, the Disturbed Sleep subtype demonstrated increased wakefulness (more wake time [p&lt; 0.001] and wake after sleep onset [p=0.001]), higher beta frequency EEG power (14.33-20.0 Hz [p=0.025] and 20.33-35.0 Hz [p=0.004]), and less deep sleep (higher average [p=0.001] and NREM-specific [p=0.044] ORP, less time with ORP from 0.50-0.75 [p=0.004] and 0.75-1.00 [p=0.015], and more time from 2.20-2.25 [p=0.017] and 2.25-2.50 [p=0.0005]). The Excessively Sleepy subtype had more severe hypoxemia, including greater hypoxic burden (p=0.002) and lower average SpO2 (p=0.002) and minimum SpO2 (p=0.0002) compared to other subtypes.

Conclusion
Differences in physiological characteristics, including ORP-related traits, were observed among symptom subtypes. Results suggest that characteristics indicative of increased wakefulness may distinguish those with the Disturbed Sleep subtype, whereas more severe hypoxemia may characterize the Excessively Sleepy subtype. Future investigations into underlying molecular causes of symptom subtypes, particularly the Excessively Sleepy, are warranted given evidence of associations with outcomes such as cardiovascular disease.

Support (if any)
SAGIC Investigators (Ayas N, Chen NH, Cistulli P, de Chazal P, Gislason TG, Han F, Hirsch-Allen AJ, Keenan BT, Li QY, Magalang UJ, Maislin G, Mazzotti DR, McArdle N, Mindel J, Pack AI, Penzel T, Schwab RJ, Singh B, Sutherland K); NIH P01 HL094307
0433 Home sleep apnea testing in patients with a LVAD: Is it feasible?
Authors: Pusalavidyasagar Snigdhasmrithi , Airhart Sophia , Kay Jenna , Christophy Antonio , Sun Benjamin , Mudy Karol , Castleberry Anthony , Emerson Dominic , Hyden Marshall , Shaffer Andrew , Mutschler Melinda , Alexy Tamas 
Published: May 2023

Abstract

Introduction
Sleep related breathing disorders, including central sleep apnea (CSA), are frequent in patients with heart failure however, only limited data is known about the effect of left ventricular assist device (LVAD) placement on OSA and even less about the accuracy of home sleep apnea testing in this population (HSAT). Performing the gold standard polysomnography (PSG) is challenging in this cohort due to logistics, especially during the COVID-19 pandemic. Extending HSAT to the LVAD population would be beneficial, yet initial tests with the WatchPat® were deemed inconclusive. We decided to evaluate the validity of NOX-T3 device for HSAT compared to PSG.

Methods
This was a single center prospective, observational study that included LVAD patients who screened positive on the STOP-BANG questionnaire. A sleep study was indicated based on consultation with a sleep physician and a standard PSG was ordered. During the PSG, the NOX-T3 was also applied with the results analyzed and compared after test completion.

Results
In this preliminary analysis, 4 patients (3 male, 1 female) with a LVAD completed a PSG along with the NOX-T3. The overall severity of sleep apnea indicated by apnea hypopnea index during the PSG and the respiratory event index during the NOX-T3 were similar in this small cohort. In 2 of the 4 patients, the oximetry finding (minutes with oxygen saturations at or below 88%) were also similar during both the PSG and the NOX-T3.

Conclusion
Based on this preliminary analysis, data obtained with the NOX-T3 system were valid and compared well to the standard of care PSG in patients with a LVAD. We plan to enroll at least 10 patients in this ongoing trial, further studies will be needed to validate these results. Performing HSAT with the NOX-T3 in this unique population if PSG is not feasible would be of significant value given the morbidity of sleep apnea in this population.

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0435 Machine-learned combination of ventilatory, hypoxic, and arousal burdens classifies daytime sleepiness better than AHI
Authors: Wickramaratne Sajila , Kam Korey , Tolbert Thomas , Kim Yun Soung , Varga Andrew , Ayappa Indu , Rapoport David , Parekh Ankit 
Published: May 2023

Abstract

Introduction
The apnea-hypopnea index (AHI), the current severity metric used clinically for diagnosing obstructive sleep apnea (OSA), does not correlate well to daytime sleepiness measured via the Epworth Sleepiness Scale (ESS). Here, we assessed whether a machine-learned combination of possibly independent metrics across ventilatory/hypoxic/arousal domains would be better associated with ESS than the AHI using data from 3 large cohorts.

Methods
Polysomnography data were analyzed from The Sleep Heart Health Study (SHHS), The Multi-Ethnic Study of Atherosclerosis (MESA), and The Osteoporotic Fractures in Men (MrOS) Study. A total of N=6618 (39.9% female; age 68.7±6.6) subjects had valid data (ESS and good quality airflow/EEG/SpO2). Ventilatory burden was evaluated using a derived flow signal that utilized the sum of thoracic and abdominal effort signals for SHHS and was evaluated using the Nasal Cannula/Pressure Transducer signal for the MrOS and MESA data. Hypoxic burden was calculated as the area between the baseline and the SpO2 trace for any episode with &gt;= 3% desaturation. Arousal burden was defined as the manually scored arousal index (number/hr.). Based on a cut-off of ESS(ESS&gt;= 10), sleepiness was coded present or absent and was the primary outcome. Data were analyzed in two ways: using all 3 cohorts as train (70%) and test (30%), and by permutations and combinations of the 3 cohorts (70/30 split; e.g., SHHS for training, MESA and MrOS for test). Model performance metrics were the area under the receiver operating characteristic curve (AUROC) and %accuracy. For comparison, a logistic regression model using AHI3a (3% desaturation and/or EEG arousal) was fit.

Results
The logistic regression model (AHI3a) classified sleepiness with an AUROC of 0.51±0.07. The random forest model trained on 70% of all 3 cohorts achieved the highest AUROC of 0.88±0.07 (mean accuracy of 85.1± 2.13%), whereas the permutations and combinations of the 3 datasets resulted in an average AUROC of 0.63 ±0.12 (mean accuracy of 76.4±6.57%).

Conclusion
The machine-learned combination of ventilatory/hypoxic/arousal burdens classifies daytime sleepiness in OSA better than AHI3a across data from 3 large cohorts. These results suggest that OSA severity measured using machine-learned combination of ventilatory/hypoxic/arousal burdens better explains the variability in daytime sleepiness.

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0436 Obstructive Sleep Apnea (OSA) Patient Journey: Retrospective Analysis of Real-world Data
Authors: Wickwire Emerson , Zhang Xuan , Munson Sibyl , Benjafield Adam , Payombar Mojgan , Patil Susheel 
Published: May 2023

Abstract

Introduction
OSA affects about 30% of US adults and up to 90% remain undiagnosed and untreated. This study aimed to characterize the OSA patient journey by identifying the most common OSA care pathways in the U.S. We also sought to compare time from diagnosis to treatment initiation between groups.

Methods
Data was extracted from a national administrative claims database (01/01/2016–02/28/2020). Inclusion criteria included age ≥18 years and 12 months continuous enrollment before/after the first OSA diagnosis (index date). OSA was defined as ICD-10 diagnosis preceded by HSAT, in-lab PSG, and/or split-night PSG within the prior 12 months. Exclusion criteria included prior OSA diagnosis/treatment or central sleep apnea. Patient pathway, demographics (at time of OSA diagnosis), timeframes, and comorbidities were assessed. Associations between sex, region, payer, and median patient journey times were investigated using generalized linear models adjusted for baseline characteristics.

Results
A total of 86,827 OSA patients (45.1% female; median age, 50±11.8) were identified, of which 60.8% initiated PAP therapy, 1.5% received an oral appliance, and 37.6% initiated neither treatment within the year following diagnosis. For patients initiating PAP, the most common care pathways identified for patients, and their median time to treatment initiation were HSAT-only (23.4%, 35 days), PSG+titration (22.9%, 58 days), split-night titration (16.8%, 28 days), PSG-only (11.2%, 37 days), HSAT+HSAT (6.9%, 37 days), titration+titration (3.9%, 31 days) and HSAT+titration (3.5%, 75 days). Relative to patients in PSG-only, individuals in HSAT-only were more likely to initiate PAP (56.1% versus 33.6% initiation). Longer timeframes from sleep test to PAP initiation were observed for patients with commercial insurance versus Supplemental Medicare (OR: 95% CI, 1.10: 1.07–1.14) and females (1.05: 1.04–1.06). There were significant differences in patient timeframes according to region (p&lt; 0.00001). Notable patterns of differences in journey time and PAP initiation were observed based on patient Metropolitan Statistical Area (MSA) diversity and MSA median household income levels, when combined.

Conclusion
This is the first national analysis to characterize common OSA treatment pathways. Time to treatment initiation varied widely between OSA care pathways. Patient sex, region, payer, and household income were associated with time to treatment initiation.

Support (if any)
Primasun
0437 Obstructive Sleep Apnea Symptom Subtypes and Hypoxic Burden Independently Predict Distinct Cardiovascular Outcomes
Authors: Mazzotti Diego , Magalang Ulysses , Keenan Brendan , Mindel Jesse , Younes Magdy , Penzel Thomas , Pack Allan , de Chazal Philip 
Published: May 2023

Abstract

Introduction
Studies on heterogeneity of obstructive sleep apnea (OSA) have identified clinically relevant symptom-based subtypes and novel OSA-specific nocturnal hypoxemia measures. Evidence suggests that moderate-severe OSA patients with the excessively sleepy subtype have increased risk of incident major adverse cardiovascular events (MACE; composite of coronary heart disease, heart failure, stroke, or cardiovascular mortality) and that OSA-specific hypoxic burden (HB) is associated with increased risk of cardiovascular disease (CVD) mortality. However, no study has comprehensively examined their combined impact. This study provides a systematic assessment of the individual and combined contribution of these factors on incident CVD risk, addressing an important gap in evidence.

Methods
Participants from the Sleep Heart Health Study with high-quality oxygen saturation, OSA severity quantified by apnea-hypopnea index (AHI), and symptom data were included. Latent class analysis on 14 symptoms was used to classify participants with moderate-severe OSA (AHI≥15) into subtypes. HB was calculated from respiratory event-related hypoxia and sleep time. Cox proportional hazards models were used to assess the relative contributions of OSA symptom subtypes and HB (natural log transformed) on risk for CVD mortality and MACE, adjusted for demographic and CVD risk factors. Analyses were performed in both CVD-free participants and all participants (adjusted for CVD at baseline).

Results
A total of 5,027 participants were analyzed, with median follow-up of 11.6 years (CVD mortality) and 11.3 years (MACE). HB was independently associated with CVD mortality in all participants (HR[95% CI] = 1.44 [1.06-1.97]; p=0.021) and CVD-free participants (1.62 [1.12-2.35]; p=0.010) controlling for symptom subtype. Conversely, symptom subtypes were independently associated with MACE incidence among CVD-free participants, controlling for HB, with the excessively sleepy participants having nearly two-fold higher risk (HR[95% CI] = 1.98 [1.26-3.10]; p=0.003) compared to those without OSA.

Conclusion
OSA symptom subtypes and HB are independently associated with distinct CVD-related endpoints. Higher HB was associated with cardiovascular mortality, controlling for symptom subtype. The excessively sleepy subtype was at higher risk of new MACE, controlling for HB. Thus, both factors are important for understanding OSA-related CVD risk.

Support (if any)
AHA (20CDA35310360), NIH (P01HL094307, U01HL53916, U01HL53931, U01HL53934, U01HL53937, U01HL53938, U01HL53940, U01HL53941, U01HL64360 R24 HL114473, 75N92019R002).
0440 Peripheral arterial tonometry–based measures of obstructive sleep apnea in Black, Mexican American and non-Hispanic White adults
Authors: Leng Yue , Peltz Carrie , Redline Susan , Stone Katie , O'Bryant Sid , Yaffe Kristine 
Published: May 2023

Abstract

Introduction
Racial/ethnic differences may exist in sleep quality and disorders, but there are limited data directly comparing objective measures of obstructive sleep apnea (OSA) among Black, Mexican American (MA) and non-Hispanic White (NHW) populations.

Methods
To date, the ongoing Health & Aging Brain among Latino Elders (HABLE)-Dormir study has enrolled 761 participants using a community-based participatory research approach. Here we describe OSA indices assessed by in-home assessments using WatchPAT, a Peripheral Arterial Tonometry (PAT)-based home sleep testing system that is validated for the diagnosis of OSA.

Results
Participants had a mean age of 65.6+/-8.2 (50-90) years, comprised of 64% women; 34% MA, 24% Black and 42% NHW adults. Over half (52.0%) of the participants had moderate or more severe OSA as defined by the respiratory event index (REI based on 3% desaturations) of &gt;=15/hour, 73.1% with REM-OSA (REM-REI &gt;=15/hour) and 40.6% with NREM-OSA (NREM-REI &gt;=15/hour). The median of the average snoring volume through the night was 41 (40-61) dB. The median percentage of sleep time spent with oxygen saturation below 90% (SpO2&lt; 90%) was 1.0%. After adjustment for age, sex, Body Mass Index, cognitive status, and history of hypertension, diabetes, stroke and heart attack, Black and MA participants were 71% and 55% more likely to have REM-OSA compared to NHW participants (p=0.04), but had similar prevalence of NREM-OSA (p=0.80) and overall OSA (p=0.32). The adjusted mean percentage of sleep time spent with over 40dB snoring volume was higher among Black (22.7%, p=0.03) and MA adults (21.2%, p=0.11) than NHW adults (18.5%). The adjusted mean prevalence of nocturnal hypoxemia (SpO2&lt; 90% time &gt;= 1%) was similar among Black (48.2%), MA (51.7%) and NHW (50.0%) adults; p=0.83.

Conclusion
In this middle-to-older-aged population, PAT-based measures of OSA indicate a higher prevalence in minoritized adults of REM-specific sleep apnea, a phenotype associated with increased rates of hypertension and mortality. Home-based measures that do not distinguish between REM and NREM respiratory events may underestimate sleep apnea in these groups.

Support (if any)
This research was supported by National Institutes of Health grant R01AG066137.
0448 Telemedicine Management of Obstructive Sleep Apnea Disorder: A Randomized Controlled Trial
Authors: Xu Liyue , Yi Huijie , Zhang Chi , Keenan Brendan , Pack Allan , Han Fang , Kuna Samuel 
Published: May 2023

Abstract

Introduction
Previous studies assessed different components of telemedicine instead of the whole telemedicine management pathway for OSA. The current study aimed to demonstrate that telemedicine management was not clinically inferior to in-person care in China based on the change in Functional Outcomes of Sleep Questionnaire (FOSQ) score following three months of an auto-adjusted positive airway pressure (APAP) treatment.

Methods
Adults suspected of OSA were randomized to telemedicine (n=178) or in-person (n=178) management. Participants with AHI ≥ 15 events/hour diagnosed by a home sleep apnea test (HSAT) were treated with an APAP with a wireless modem. The participants were followed up by call at week 1 and visit at month 1 and month 3.

Results
We measured the change in FOSQ score as the primary outcome, with an a priori noninferiority delta of -1, and the mean daily hours of objectively measured APAP adherence, with an a priori noninferiority delta of -45min/day. Of the 356 subjects enrolled, 313 (87.9%) were diagnosed with OSA, and 261 (73.3%) underwent PAP setup. The mean functional outcome score following 3 months improved 1.73 points (95%CI: 1.31, 2.14) in the telemedicine group and 2.05 points (95% CI: 1.64, 2.46) in the in-person group. The lower bound of the one-sided 95% noninferiority confidence interval was -0.812. Mean daily APAP adherence at 3 months was 243.3 minutes/night (95% CI: 223.1, 263.5) in the telemedicine arm and 241.6 minutes/night (95% CI: 221.3, 261.8) in the in-person arm. The lower bound of the one-sided 95% noninferiority confidence interval was -22.2 minutes/night. Compared to in-person management, the telemedicine pathway had lower patients cost and similar health care cost.

Conclusion
Functional outcome and treatment adherence in patients managed by a comprehensive telemedicine approach is not clinically inferior to that in patients receiving in-person care.

Support (if any)
ResMed Australia funded the APAP machines. The study was supported by the National Key R&D Program of China (Z161100002616012). Liyue Xu is supported by a grant from the National Natural Science Foundation of China (NSFC 82100104).
0451 Dronabinol Plus Acetazolamide for the Treatment of Obstructive Sleep Apnoea: A Proof of Concept and Mechanistic Exploration Study
Authors: Thomson Luke , Rankin Timothy , Mehra Sumit , Naughton Matthew , Roebuck Teanau , McDermott Elizabeth , Pattichis Andreas , Smith Rafael , Germaine Jack , Walsh Rosemarie , Bleackley Mark , Edwards Bradley , Maddison Kathleen , O'Brien Terence , Walsh Jen 
Published: May 2023

Abstract

Introduction
Current treatments for obstructive sleep apnoea (OSA) typically target the anatomical pathophysiological endotype and are either not tolerated or effective in a significant proportion of patients. Pharmaceuticals may provide an alternative therapeutic option and may address some or all of the remaining endotypes (loop gain, muscle compensation and arousal threshold). This randomised, double-blind, placebo-controlled, cross-over study examined the effect of combination acetazolamide and dronabinol (IHL-42X) at low, medium and high doses on OSA severity and the OSA endotypes.

Methods
Participants with OSA (apnoea-hypopnoea index; AHI≥15events/hr) received 1-week of IHL-42X at each of the 3 doses and 1-week of placebo, each separated by 1-week washout. The change from baseline in AHI, oxygen desaturation index (ODI), Epworth sleepiness score (ESS), and mood (profile of mood states) on the final night of each treatment arm relative to placebo were the major endpoints. Adverse events (AEs) were monitored throughout. Exploratory analyses examined the change in OSA endotypes determined from polysomnography from baseline values.

Results
Ten of 11 participants (mean baseline AHI 40.7events/hr) completed the final night of at least one treatment arm. All doses of IHL-42X demonstrated a significant reduction in AHI from baseline when compared with placebo (low, -19.7±27.1; medium, -17.5±23.3; high, -16.4±23.8 versus placebo, -2.8±21.0events/hr; all p&lt; 0.05). The change from baseline in ODI3% at the low, medium and high doses of IHL-42X (-15.2±24.8; -15.4±19.0 and -8.3±13.2events/hr, respectively) were not significantly different from placebo (-2.8±21.0events/hr). IHL-42X did not significantly alter ESS or mood. No serious AEs occurred. However, 31 mild-moderate possibly, probably or treatment related AEs occurred during IHL-42X dosing (4 at the low dose) and 4 occurred during placebo. Relative to baseline, loop gain decreased by 15, 21 and 20% (Cohen’s d all ≥0.59) at the low, medium and high doses, respectively, and collapsibility improved by 12.5% (d=1.06) at the low dose only.

Conclusion
One week of nightly IHL-42X at all doses was well tolerated, safe and associated with significant reductions in OSA severity. IHL-42X may act to reduce OSA severity by decreasing loop gain and upper airway collapsibility, particularly at the low dose.

Support (if any)
Incannex Healthcare Ltd supported this study.
0452 Mild-to-moderate OSA and mortality in general population: the modifying effect of age and cardiovascular/cerebrovascular morbidity
Authors: Vgontzas Alexandros , Karagkouni Efthalia , He Fan , Fernandez-Mendoza Julio , Li Yun , Karataraki Maria , Bixler Edward 
Published: May 2023

Abstract

Introduction
Mild-to-moderate obstructive sleep apnea (mOSA) is highly prevalent in the general population and is highly comorbid with cardiovascular and/or cerebrovascular diseases (CBVD). We examined the association between mOSA and all-cause mortality and the modifying effect of age and CBVD.

Methods
A total of 1681 adults 20-88 years old from the Penn State Adult Cohort (41.9% male, 10.5% racial/ethnic minority) were followed up for 20.1±6.2 years for all-cause mortality. The presence of mOSA was defined as an apnea/hypopnea index from 5-29.9 events/hour. CBVD was defined as a report of diagnosis or treatment for heart disease and/or stroke. Cox proportional hazards regression models were used to estimate all-cause mortality adjusted for confounders.

Results
All-cause mortality risk was significantly increased in the mOSA group in young and middle-aged adults (&lt; 60 years) (HR=1.59, 95%CI 1.08-2.04) but not in older adults (≥60 years) (HR=1.05, 95%CI 0.80-1.39). We observed a synergistic effect between mOSA and CBVD that was stronger in those &lt; 60 years (HR=3.82, 95%CI 2.25-6.48 in &lt; 60 years vs 1.86 95%CI 1.14-3.04 in ≥60 years). There was an additive effect between mOSA and hypertension in &lt; 60 but not in those ≥60 years (mOSA and hypertension HR=2.39, 95%CI 1.56-3.66 vs. 1.09 95%CI 0.75-1.57).

Conclusion
Mortality risk is increased in young and middle-aged adults with mild-to-moderate forms of OSA. The risk is even stronger in the presence of CBVD/hypertension. It appears that AHI cut-offs warranting treatment of mOSA should be adjusted based on age and prevalent clinical disorders.

Support (if any)