bluuebunny/crossref_metadata_2025_split huggingface dataset:
0543 Obstructive Sleep Apnea, Platelet Aggregation and Cardiovascular Risk
Authors: Kovbasyuk Zanetta , Ramos-Cejudo Jaime , Osorio Ricardo , Parekh Ankit , Ayappa Indu , Bubu Omonigho , Varga Andrew , Rapoport David 
Published: May 2023

Abstract

Introduction
Obstructive sleep apnea (OSA) affects pathways implicated in the pathophysiology of cardiovascular disease (CVD) by poorly understood mechanisms. Platelets are key mediators of CVD risk and thrombosis and prior studies have suggested associations with OSA. We hypothesized that markers of OSA and platelet activity may be linked, and that these associations may be influenced by CVD risk factors.

Methods
Using one of the largest repositories of sleep phenotyping and platelet aggregation data available, we assessed the association of the apnea hypopnea index (AHI4%) and platelet aggregation in 482 participants dually enrolled within the Sleep Heart and Health (SHHS) and Framingham Heart Study (FHS) Offspring cohorts. Our primary outcome was the platelet aggregation response to adenosine diphosphate (ADP) 1.0 µmol/L measured by light transmission aggregometry. Other stimulation doses and OSA-related measures were used as secondary for further validation. The relationship between the AHI and platelet aggregation was assessed using standard regression models adjusted for age, sex, years of education, BMI, smoking status, hypertension, diabetes, present CVD history, aspirin use, high-density lipoprotein (HDL) cholesterol, total cholesterol, and triglycerides. We also examined the influence of OSA and CVD-related factors such as age, sex, BMI, hypertension, OSA diagnosis (AHI4% ≥ 5), and the use of platelet modifying drugs.

Results
No associations were observed between the AHI and platelet aggregation. No associations were observed when stratifying by age (&lt; vs. ≥ 65.0), median BMI (&lt; vs. ≥ 27.85), hypertension (51.9%), or OSA diagnosis (47.1%). AHI was associated with platelet aggregation when stratifying by aspirin use (β= 0.523; p &lt; 0.001; n=65). Associations were found in the same group of aspirin users for secondary exposures: hypoxic burden (β= 0.358; p &lt; 0.001), minimum saturation (β= -0.519; p = 0.026), and the ODI3% (β= 74.672; p = 0.002).

Conclusion
Our study indicates that the AHI is not associated with platelet aggregation in the general population. Our finding that the AHI is strongly associated with platelet aggregation in participants who are on aspirin for primary prevention of CVD reinforces the need for further examining the mediator role of platelet activity in the association of OSA and CVD risk.

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0546 Patient-reported experience with a wireless patch-based polysomnography system – results from a pilot study
Authors: Schneider Hartmut , Haisma Nicola , Mueller Syuyumbeki , Oloo Maryanne , Tijssen Marij , Stockhoff Mariele , Knoops-Borm Martine , Ermers Pieter , DeFrancisco Ruben , Coughlin Steven 
Published: May 2023

Abstract

Introduction
Sleep is critical for health and wellbeing. Left untreated, sleep disorders negatively impact daily functioning and quality of life. The gold-standard for sleep monitoring and diagnosis is in-lab polysomnography (PSG). Though PSG provides a comprehensive overview of sleep, it is uncomfortable due to the amount of sensors, which prohibit movement and disturb sleep. A wireless patch-based PSG system, the Onera Sleep Test System (STS), consisting of four body-worn sensors, was recently introduced to overcome these limitations. The objective of this study is to evaluate patient-reported experience when using the Onera STS.

Methods
Forty-two patients were enrolled in Germany as part of an ongoing validation study. Participants were asked to fill in two questionnaires. The first, administed before the Onera STS sleep study, asked open-ended questions on their first impression of the device. The second, administered after the Onera STS sleep study, focused on the ease of use of the device and comfort of wearing it during the night using a 5-point Likert scale.

Results
Thirty-six patients completed the first questionnaire (85%) and 39 (93%) the second. First impression of the Onera STS was positive by 86% of patients. The size of the sensors was described as acceptable by 72%. Participants stated that the device looked more comfortable than in-lab PSG and they expected improved sleep quality and a more accurate diagnosis. After completing the PSG with the Onera STS system, 69% found wearing the four sensors comfortable, and no participant expressed strong discomfort during the sleep study. The Forehead sensor was considered the most comfortable (based on 77% stating strongly agree or agree), followed by the Abdomen sensor (74%), the Leg sensor (72%), and the Chest sensor (69%). Most participants (72%) expressed confidence in their ability to fit the sensors by themselves at home. Only one participant preferred to be supported by a technician for the application of the system.

Conclusion
The first impression of the Onera STS device were positive, and participants found it comfortable during sleep. The majority considered the application simple enough for unsupervised self-application, which can allow patients to undergo a PSG in the comfort of their own home.

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0558 Sleep Bruxism and Sleep Breathing Disorder
Authors: Han JinKyu 
Published: May 2023

Abstract

Introduction
Sleep bruxism (SB) is reported by 8-9% of the adult population and is mainly associated with rhythmic masticatory muscle activity (RMMA) characterized by repetitive jaw muscle contractions (3 bursts or more at a frequency of 1 Hz). The purpose of this study was to evaluate the relationship between the nature of sleep bruxism and the sleep breathing disoredr.

Methods
We prospectively studied 32 patients who were referred to the clinical sleep apnea laboratory for study. They underwent standard nocturnal polysomnographic examination; in addition, masticatory activity was measured with a masseter electromyogram. Patients slept in the supine and lateral decubitus positions.

Results
Nocturnal clenching was higher in patients with higher respiratory disturbance index. 28 among 32 patients were included in the criteria of obstructive sleep apnea; average respiratory disturbance index (RDI) was 12.7 280 clenches demonstrated in all patients.

Conclusion
We conclude that there is an association between sleep related breathing disorder and bruxisms that sleep position affects the incidence of both sleep disordered breathing and bruxisms, and that analysis of apneas and hypopneas and clenching events in both supine and lateral decubitus sleeping positions may be helpful.

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0567 Tirzepatide for the Treatment of OSA: Rationale and Design of the SURMOUNT-OSA Phase 3 Trial
Authors: Malhotra Atul , Bednarik Josef , Curtis Alexandra , Dunn Julia , Weaver Terri , Grunstein Ron , Fietze Ingo , Redline Susan , Bunck Mathijs C 
Published: May 2023

Abstract

Introduction
Weight reduction is a standard recommended component of OSA treatment in people with obesity or overweight; however, the challenge to achieve and maintain weight reduction has limited its clinical application outside of the benefit established after bariatric surgery. Currently no FDA-approved anti-obesity medication (AOM) has demonstrated clinically meaningful improvement in OSA severity and symptomology.

Methods
Tirzepatide is a single molecule GIP and GLP-1 receptor agonist. In SURMOUNT-1, a 72-week phase 3 clinical trial in participants with obesity or overweight, tirzepatide 15mg provided average reductions in body weight of 22.5% which occurred with beneficial effects on blood pressure, lipids, and physical functioning. In a linear meta regression model, we estimated that tirzepatide treatment would provide clinically meaningful apnea-hypopnea index decrease compared to placebo-treated participants with obesity and OSA. SURMOUNT-OSA, a placebo controlled 52-week, phase 3 trial, will investigate efficacy and safety of tirzepatide for the treatment of moderate to severe OSA (defined as AHI ≥15) in participants with obesity. SURMOUNT-OSA utilizes an umbrella master protocol and 2 Intervention-Specific Appendices (ISAs): ISA 1 includes participants with no current OSA treatment and ISA 2 includes participants using positive airway pressure therapy. Approximately 412 participants will be randomly assigned to placebo or tirzepatide across the entire master protocol, with approximately 206 participants in each ISA. While participants will receive tirzepatide or placebo based on a 1:1 randomization ratio, all participants will receive background lifestyle intervention for weight reduction.

Results
The primary endpoint for the individual ISAs is the difference in AHI response measured by polysomnography between tirzepatide and placebo arms at week 52. Secondary endpoints include hypoxic burden, functional outcomes and cardiometabolic biomarkers. The trial is utilizing a unique hierarchical functional outcomes endpoint based on Functional Outcomes of Sleep Questionnaire methodology. The trial employs wearables, such as home sleep testing and accelerometry to capture time to improvement as exploratory outcomes.

Conclusion
SURMOUNT-OSA aims to explore whether tirzepatide provides clinically meaningful improvement in obesity-related OSA by targeting an underlying etiology.

Support (if any)
Eli Lilly
0580 Patient Experiences With Sodium Oxybate Therapy for Narcolepsy: A Social Listening Analysis
Authors: Horsnell Matthew , Zhang Enming , Cook Rachelle , Dougherty Lauren , Shenk Allison Foley , Ascencion Frederik , Morse Anne , Ortiz Luis , Li Wei , Wassman E Robert , DeFelice Christopher , Picone Maria 
Published: May 2023

Abstract

Introduction
Narcolepsy is a disorder of hypersomnolence with intermittent periods of sleep, hallucinations, and sleep paralysis. Social listening (SL) analyzes real-world data on social media to provide information on disease symptoms and impacts to inform clinicians about a community’s unmet needs. This research used SL with a proprietary artificial intelligence (AI) engine, which leverages natural language processing (NLP) to understand experiences of people living with narcolepsy treated with sodium oxybate (SO), a twice-nightly medication.

Methods
Using the proprietary AI engine to analyze text-based conversations, we evaluated 25,018 posts/comments from 15,280 participants which occurred from August 2011 to October 2022 from the subreddit r/Narcolepsy and a private Facebook group. Using a clinical entity recognition tagger, leveraging medicine ontology, conversations were filtered by mentions of (1) second dosage (e.g., second dose, 2nd) and (2) sodium oxybate (e.g., Xyrem, SO) to build a co-occurrence network for conversations discussing second doses of SO. Surveys and interviews were used to document patient SO experiences (Facebook, Discord channels, other networked contacts).

Results
Of 4275 subreddit users who mentioned SO, 398 (9.3%) communicated challenges with taking a second SO dose. The co-occurrence network revealed that second SO dose was co-mentioned with physical (e.g., nausea, headache) and mental (e.g., anxiety, depression, eating disorder) conditions. Of survey participants (N = 87 completed: patients, n = 85; caregivers, n = 2), 75% reported missing the second SO dose; effects included poor sleep quality, increased daytime sleepiness, mental health issues (especially depression), muscle spasms, work/school absences, and brain fog. Injuries resulting from waking to take the second dose (e.g., falls, stitches, concussions) were reported by 32%. Taking the second dose late (&gt;4 hours after) was reported by 59% of patients. Effects of late dosing included grogginess, headache, and oversleeping, leading to school/work tardiness and missed responsibilities. When asked if a once-at-bedtime, premeasured SO dose would be safer, 76% of respondents agreed/strongly agreed.

Conclusion
The second nightly SO dose is associated with sleep-related issues for people with narcolepsy and their caregivers. Both the SL analysis and survey revealed that a missed/delayed second dose of SO decreased daily functioning, quality of life, and physical health.

Support (if any)
Avadel Pharmaceuticals.
0581 Patient Preferences and Nocturnal Experiences With Oxybate Therapy for Narcolepsy: RESTORE Study Interim Analysis
Authors: Roy Asim , Harsh John , Ajayi Akinyemi , Stern Thomas , Dubow Jordan , Gudeman Jennifer 
Published: May 2023

Abstract

Introduction
Sodium oxybate (SXB) is a standard-of-care treatment for adults with narcolepsy. Existing oxybate formulations are immediate release (IR), requiring patients to awaken for a second dose 2.5–4 hours after the first bedtime dose. Once-nightly SXB (ON-SXB; FT218), an investigational extended-release formulation, replaces this middle-of-the-night dosing with a once-at-bedtime regimen. RESTORE (NCT04451668) is an open-label/switch study evaluating the safety/tolerability of ON-SXB and patient preferences for ON-SXB or IR oxybate.

Methods
RESTORE includes participants aged ≥16 years with narcolepsy type 1 or 2 who completed the phase 3 REST-ON trial, were on stable-dose (≥1 month) IR oxybate, or were oxybate-naive. Initial doses for participants switching from IR oxybate are equivalent/closest to the previous total dose/night; incremental adjustments (1.5 g/week; maximum, 9 g/night) are allowed. A nocturnal adverse event (AE) questionnaire about switch participants’ IR oxybate experience in the previous 3 months was completed at baseline. Switch participants completed the preference questionnaire after 3 months of ON-SXB treatment.

Results
Data available from preference questionnaires (n=78) and nocturnal AE questionnaires (n=130) were analyzed at the interim data cutoff (01 July 2022). Most common AEs thus far were nausea, headache, and somnolence. The once-nightly dosing regimen was preferred by 93.6% (73/78) of participants. The second nightly IR oxybate dose was unintentionally missed in the previous 3 months by 65.4% (85/130) of switch participants; 80.2% (73/91) who intentionally and/or unintentionally missed the second dose felt worse the next day. Participants who took their second nightly IR oxybate dose &gt;4 h after the first dose (51/130 [39.2%]) reported being somewhat, quite a bit, or extremely groggy/unsteady the next morning (26/51 [51.0%]). Inconvenience of the second dose was reported by 70.8%. Other issues related to the second dose were anxiety (29.2%) and the need to be woken by someone else (23.1%). In the past 3 months, 118 participants (90.8%) arose from bed after waking to take the second dose; 9 of these participants reported having fallen, with 5 reporting injuries.

Conclusion
These interim RESTORE data demonstrate patient preference for once-at-bedtime dosing of ON-SXB and indicate treatment burden associated with twice-nightly IR oxybate.

Support (if any)
Avadel Pharmaceuticals
0615 Racial/Ethnic and Sex Differences in Circadian Rest-Activity Rhythm Patterns: Findings from a Sample of the US Population
Authors: Narcisse Marie-Rachelle , Refinetti Roberto , Seixas Azizi , Moise Rhoda , Locklear Clarence , Moore Jesse , Turner Arlener D , Rogers April , Jean-Louis Girardin 
Published: May 2023

Abstract

Introduction
Circadian disruptions are associated with increased risk for morbidity and mortality. However, it is unclear whether these associations vary by race/ethnicity. We aim to explore, 1) Examine whether rest-activity rhythm (RAR) patterns vary across race/ethnicity among a representative sample of the US adult population, and 2) Examine the interaction of race/ethnicity and sex in RAR patterns.

Methods
The study was based on the National Health and Nutrition Examination Survey (2013–2014) with data from participants who wore a physical activity monitor (PAM ActiGraph accelerometer model GT3X+) continuously for seven consecutive days. After excluding pregnant participants and those with sleep minutes &lt; 120 and &gt;1200, the analytic sample included was 4,722 adults. The cosinor method was used based on PAM minutes time-series data to RAR outcome variables: mesor, amplitude, acrophase. and robustness. The main predictor of interest was race/ethnicity (Asian, Black, Hispanic, multi/other, and White). A sex-race/ethnicity interaction was tested to assess if racial/ethnic differences in RAR patterns differ between males and females. Other covariates included were age, marital status education federal poverty level, and employment status. Eight adjusted Generalized linear models (GLM) : four with race/ethnicity as the main predictors and four multiplicative interaction models with the product term of race/ethnicity and sex. An adjusted Wald test was used to test for interaction.

Results
Compared with White adults, Hispanic adults had increased mesor levels (ß=0.10; 95% CI:0.07;0.13), increased RAR amplitude (ß=0.10; 95% CI:0.06;0.13), and increased robustness (ß=0.07; 95% CI:0.03;0.11) whereas Black adults had decreased amplitude (ß=-0.11; 95% CI:-0.16;-0.07) and decreased robustness ( (ß= -0.14; 95% CI:-0.20; -0.09) compared to White adults. Similarly, Asians had decreased amplitude (ß=-0.06; 95% CI:-0.10;-0.01) and decreased robustness (ß=-0.11; 95% CI:-0.16; -0.06). A significant sex-race/ethnicity interaction was found for amplitude F(4,12)=3.94;p=0.029 and robustness (4,12)=6.02;p&lt; 0.001.

Conclusion
RAR is associated with race/ethnicity, and this association varies by sex. Notably, Hispanic adults had increased mesor, amplitude, and robustness compared to Whites. Conversely, Black and Asian populations shared decreased amplitude and robustness compared to Whites. Future studies may consider further investigation of circadian health by race/ethnicity and sex for community intervention.

Support (if any)
K01HL135452, K07AG052685, R01AG072644, R01HL152453, R01MD007716, R01HL142066, R01AG067523, R01AG056031, and R01AG075007
0618 Are we failing our night shift workers?: A look into the unmet needs of our night shift work force
Authors: Spector Tori , Neuenschwander Eva , Kalmbach David , Sagong Chaewon , Drake Christopher , Cheng Philip 
Published: May 2023

Abstract

Introduction
Many night shift workers experience poor health and safety concerns associated with circadian misalignment, which is driven by an inverted sleep-wake schedule. This work schedule leads to symptoms of excessive sleepiness and insomnia which have devastating consequences, including job dissatisfaction and social impairments. Past research has focused on circadian misalignment as the predominantly cause of shift work disorder; however, circadian misalignment is only one factor in the ecology of night shift work. A more inclusive model would consider other socioecological factors that may also influence the feasibility and effectives of interventions. This study utilized a patient-centered framework to probe the impacts of night shift work beyond symptoms of shift work disorder.

Methods
Five focus groups comprising of 20 individuals with shift work disorder (ICSD-3 diagnostic criteria) were conducted. Participants were asked about their job satisfaction levels, employee support, and problems associated with shift work. Thematic analysis was done, and sample quotes were pulled to indicate levels of support and other barriers associated with shift work.

Results
Analysis revealed four main themes regarding non-sleep related impairments of night shift work: isolation, poor health, cognitive and mood disorders, and altered sense of self. Participants reported greater instances of loneliness, weight fluctuations, short tempers, alterations in self-image, and other unfavorable effects from working nights. A significant number of participants additionally indicated very little to no support or education from employers regarding their night shift work.

Conclusion
The combined results of the focus groups highlight the unmet needs of night shift workers. These data indicate that night shift workers are an under-served and under-resourced sector of our workforce, and that circadian interventions for shift workers should measure impact on quality of life beyond sleep and sleepiness. Given their critical roles in sustaining 24-7 access to essential services, it is imperative that we develop evidence-based interventions for night shift workers.

Support (if any)
Support for this study was provided from the National Institute of Health (R41HL163783) and the American Academy of Sleep Medicine Foundation (245-SR-21) awarded to Dr. Philip Cheng.
0620 Dim Light Melatonin Onset Analysis in Individuals Diagnosed with Delayed Sleep-Wake Phase Disorder (DSWPD)
Authors: Brzezynski Jennifer , Johnson Caroline , Goldberg Abigail , Miller Cameron , Kaden Alyssa , Smieszek Sandra , Polymeropoulos Christos , Birznieks Gunther , Polymeropoulos Mihael 
Published: May 2023

Abstract

Introduction
We are conducting a double-blind, randomized, clinical study in Delayed Sleep-Wake Phase Disorder (DSWPD) participants with extensive clinical phenotyping. We evaluated screening Dim Light Melatonin Onset (DLMO) assessments in participants with a DSWPD diagnosis to determine the proportion of participants with and without a circadian delay.

Methods
Delayed DLMO is DLMO occurring after or within 30 minutes before desired bedtime, and after 21:30. Each DLMO assessment consisted of eight saliva collections performed at five, four, three, two, and one hour before bedtime, at planned bedtime, and one and three hours after bedtime. Salivary DLMO assessments were distributed to participants at Visit 1 (screening) and Visit 3 (treatment) with a questionnaire to record planned and actual collection times. Participants were instructed to wear blue-light blocking glasses during the assessment period. The Morningness-Eveningness Questionnaire (MEQ) was also completed by participants at V1 to evaluate circadian and sleep rhythm patterns. DLMO was calculated for each phase assessment and defined as the clock time when the melatonin concentration exceeded the mean of three low consecutive values, plus twice the standard deviation of these points.

Results
Thirty-four participants with DSWPD completed the screening DLMO assessment, 33 of which had a delayed DLMO (97.06%). Sub-analyses were conducted on participants with DSWPD who had delayed DLMO (n = 33). Within this subset, the average DLMO time was 23:52 (SD = 1:58) and the average MEQ score was 34.27 (SD = 10.39). Of these 33 participants, 14 had a DLMO time after 00:00 (42.42%).

Conclusion
These initial data indicate that, on average, participants with DSWPD that completed the screening DLMO assessment had delayed DLMO. Further analyses show that almost half of this subset had a significantly delayed DLMO (00:00 or later). This study is currently ongoing and blinded. Further data will be analyzed as more participants enroll. ‘Phase typing’ will be important in further understanding the underlying pathophysiology and in the treatment selection for patients with DSWPD.

Support (if any)
This work was supported by Vanda Pharmaceuticals Inc.